PMID- 1613491 TI - Purification and lectin-binding properties of s-laminin, a synaptic isoform of the laminin B1 chain. AB - The extracellular matrix (ECM) at the vertebrate neuromuscular junction is a repository of functionally important molecules, some of which can regulate the formation of synapses during regeneration. One candidate molecule is s-laminin, a 185-kDa homologue of the laminin B1 chain. Whereas several members of the laminin family are present throughout the ECM ensheathing muscle fibers, immunoreactivity for s-laminin is found selectively at synaptic sites in adult and embryonic rats, and is detectable at a time when synaptogenesis is taking place during development. We have reported previously that a rat schwannoma cell line, D6P2T, produces and releases large amounts of s-laminin in culture. We have now purified s-laminin from medium conditioned by these cells by using a simple three-step procedure. Serum-free, conditioned medium is separated by ion-exchange chromatography on DEAE-Sephacel, followed by size-exclusion chromatography on 500 HR-Sephacryl. Finally, s-laminin is dissociated from other ECM components by agarose gel electrophoresis under reducing conditions and recovered in solution by extracting slices of agarose gel. The purified preparation displays one silver stained band that is recognized by three monoclonal antibodies known to bind to different epitopes on s-laminin. Lectin-binding studies demonstrate that s laminin is a glycoprotein and bears many of the carbohydrate moieties present on the B1 and B2 chains of laminin. Thus, the three 185-220-kDa members of the laminin family are related in both their protein and carbohydrate domains. PMID- 1613492 TI - Adult rat retina interneurons synthesize GD3: GD3 expression by these cells is regulated by cell-cell interactions. AB - GD3, a ganglioside of the lactosyl series, is prevalent in rat retina neuronal cells. We studied here whether rat retina neurons synthesize their own surface GD3 or if they acquire it from Muller glia cells. We analyzed the activity of GD3 synthase and the in vivo labeling of gangliosides from N-[3H]acetylmannosamine in adult rat retinas after selective destruction of Muller glia cells with the gliotoxic alpha-D,L-aminoadipate (AAA). Immunostaining of rat retina sections and western blot analysis with an antivimentin antibody confirmed the gliotoxic effect of AAA. Neither GD3 synthase activity nor the in vivo labeling of GD3 and other gangliosides was significantly affected by AAA, indicating that neuronal cells synthesize their own GD3. We next analyzed the regulation of the expression of GD3 by these neurons in culture. About 80% of freshly dissociated cells from retina of 4-day-old rats (R4) immunoexpress surface GD3. After 3 days in dispersed cell culture conditions, GD3 expression was under the limit of detection in 80% of neuronal cells, indicating a failure of these cells to maintain the expression of surface GD3 in these experimental conditions. Most flat Muller glia-derived cells present in these cultures were GD3 positive. Surface GD3 was detected in approximately 60% of neuronal cells dissociated from R4 tissue that was developed in vitro as an organ culture for 3 days. Likewise, approximately 50% of neurites that had grown out from R4 retinal explants within 3 days in culture and whose neuronal character was indicated by immunoexpression of growth-associated protein GAP-43 were GD3 positive. These findings suggest that the tissue organization and/or specific interactions modulate GD3 expression in neuronal cells. Under dispersed-cell culture conditions, c-pathway gangliosides (GQ1c and GT1c), which are built up from the sialylation of GD3 and later completion of the oligosaccharide backbone, were detected in approximately 60% of neuronal cells, suggesting a maintenance of production of GD3 as an intermediate for gangliotetraosyl gangliosides. PMID- 1613493 TI - Toxic effects of iron for cultured mesencephalic dopaminergic neurons derived from rat embryonic brains. AB - Iron, a transition metal possibly involved in the pathogenesis of Parkinson's disease, was tested for its toxic effects toward cultures of dissociated rat mesencephalic cells. When cultures were switched for 24 h to serum-free conditions, the effective concentrations of ferrous iron (Fe2+) producing a loss of 50% of dopaminergic neurons, as quantified by tyrosine hydroxylase (TH) immunocytochemistry, TH mRNA in situ hybridization, and measurement of TH activity, were on the order of 200 microM. High-affinity dopamine (DA) uptake, which reflects integrity and function of dopaminergic nerve terminals, was impaired at significantly lower concentrations (EC50 = 67 microM). Toxic effects were not restricted to dopaminergic neurons inasmuch as trypan blue dye exclusion index and gamma-aminobutyric acid uptake, two parameters used to assess survival of other types of cells present in these cultures, were also affected. Protection against iron cytotoxicity was afforded by desferrioxamine and apotransferrin, two ferric iron-chelating agents. Normal supplementation of the culture medium by serum proteins during treatment was also effective, presumably via nonspecific sequestration. Potential interactions with DA were also investigated. Fe2+ at subtoxic concentrations and desferrioxamine in the absence of exogenous iron added to the cultures failed to potentiate or reduce DA cytotoxicity for mesencephalic cells, respectively. Transferrin, the glycoprotein responsible for intracellular delivery of iron, was ineffective in initiating selective cytotoxic effects toward dopaminergic neurons preloaded with DA. Altogether, these results suggest (a) that ferrous iron is a potent neurotoxin for dopaminergic neurons as well as for other cell types in dissociated mesencephalic cultures, acting likely via autoxidation into its ferric form, and (b) that the presence of intra- and extracellular DA is not required for the observed toxic effects. PMID- 1613494 TI - Mapping of histamine H1 receptors in the human brain using [11C]pyrilamine and positron emission tomography. AB - We have studied the characteristics of carbon-11 labeled pyrilamine as a radioligand for investigating histamine H1 receptors in human brain with positron emission tomography (PET). [11C]Pyrilamine is distributed evenly in proportion to cerebral blood flow at initial PET images. Later (after 45-60 min), 11C radioactivity was observed at high concentrations in the frontal and temporal cortex, hippocampus, and thalamus, and at low concentrations in the cerebellum and pons. The regional distribution of the carbon-11 labeled compound in the brain corresponded well with that of the histamine H1 receptors determined in vitro in autopsied materials. In six controls, the frontal and temporal cortices/cerebellum ratio increased during the first 60 min to reach a value of 1.22 +/- 0.071. Intravenous administration of d-chlorpheniramine (5 mg) completely abolished the specific binding in vivo in the frontal cortex and temporal cortex (cortex/cerebellum ratio, 0.955 +/- 0.015). The availability of this method for measuring histamine H1 receptors in vivo in humans will facilitate studies on neurological and psychiatric disorders in which histamine H1 receptors are thought to be abnormal. PMID- 1613495 TI - Glucocorticoids exacerbate hypoxic and hypoglycemic hippocampal injury in vitro: biochemical correlates and a role for astrocytes. AB - The acute secretion of glucocorticoids is critical for responding to physiological stress. Under normal circumstances these hormones do not cause acute neuronal injury, but they have been shown to enhance ischemic and seizure induced neuronal injury in the rat brain. Using fetal rat hippocampal cultures, we asked whether hypoxic and hypoglycemic cell damage in vitro could be exacerbated by direct exposure to corticosterone (CORT). Each of these insults alone damaged neuronal cells, whereas 4-6 h of hypoxic treatment could damage age matched astrocytes if glucose was reduced or omitted. Ischemic-like injury to both cell types could be attenuated by pretreatment with high (30 mM) glucose. Exposure to 100 nM CORT did not affect cell viability under control conditions but enhanced both hypoxic and hypoglycemic neuronal injury. In both cases, pretreatment with high glucose abolished this CORT-mediated synergy. In astrocyte cultures, CORT exacerbated both hypoxic and hypoglycemic injury and this effect was also attenuated by high-glucose pretreatment. Identical 24-h CORT treatment caused a 13% reduction in glucose uptake in astrocytes and a 38% reduction in glycogen content, without affecting the level of intracellular glucose. Thus, CORT could endanger both neurons and astrocytes in mixed hippocampal cultures and this effect emerged only under conditions of substrate depletion. The metabolic disruption in astrocytes by CORT further suggests that the ability of CORT to exacerbate neuronal injury may be due in part to impaired glial cell function. PMID- 1613496 TI - Ethanol-induced increase in endogenous dopamine release may involve endogenous opiates. AB - The effect of opiate peptides on basal and potassium-stimulated endogenous dopamine (DA) release from striatal slices was studied in vitro. Dual stimulation of the striatal slices gave a reproducible increase in DA release that was calcium dependent. Addition of the delta-opiate receptor agonists Met5 enkephalin, [D-Ala2,D-Leu5]enkephalin (DADLE), and [D-Ser2]Leu-enkephalin-Thr (DSLET), increased the basal DA release without affecting potassium-stimulated release in a dose-dependent manner. The effect of DADLE was antagonized by the addition of naloxone. In contrast, the mu-opioid receptor agonist [D-Ala2,N MePhe4,Gly-ol5]enkephalin (DAGO) and the epsilon-opioid agonist beta-endorphin inhibited the stimulated DA release without changing the basal release. The inhibitory effect of DAGO on potassium-stimulated release was antagonized by naloxone. The addition of ethanol (75 mM) to the incubation media produced a delayed increase of both the basal and stimulated DA release. There was no change in stimulated DA release when the change in basal release was subtracted, suggesting that ethanol produced a dose-dependent, selective increase in basal DA release. Naloxone and the selective delta-opiate antagonist ICI 174864 inhibited the ethanol-induced increase in basal DA release. Naloxone and ICI 174864 added alone did not alter either basal or stimulated DA release. We therefore suggest that the ethanol-induced increase in basal DA release is an indirect effect involving an endogenous delta-opiate agonist. PMID- 1613497 TI - Temporal profiles of nerve growth factor beta-subunit level in rat brain regions after transient ischemia. AB - To determine the role of nerve growth factor (NGF) in ischemic brain damage, we measured the temporal and regional changes in the level of NGF in the hippocampal subfields, the cerebral cortex, the striatum, and the septum at 1, 2, 7, and 30 days after transient forebrain ischemia using a highly sensitive sandwich-type enzyme immunoassay system for the beta-subunit of mouse 7S NGF (beta-NGF). We also analyzed glial fibrillary acidic protein immunoreactivity in the hippocampus to ascertain the contribution of reactive astrocytes to NGF production after an ischemic insult. In the CA1 subfield of the hippocampus, the level of beta-NGF decreased slightly 2 days after ischemia (not significant), at which time CA1 pyramidal cell loss began to occur, and increased by 40% 30 days after ischemia (p less than 0.05). A marked increase in glial fibrillary acidic protein-positive astrocytes in the CA1 subfield 2-30 days after ischemia suggests that the reactive astrocytes participated in a gradual increase in the level of beta-NGF after recirculation. The level of beta-NGF in the dentate gyrus decreased transiently 2 days (p less than 0.05) and 7 days (p less than 0.01) after ischemia, followed by recovery to the level of control animals 30 days after ischemia. The level of beta-NGF in the septum gradually decreased 7 days (-27%, p less than 0.05) and 30 days (-43%, p less than 0.01) after ischemia. The levels of beta-NGF in the cerebral cortex and striatum remained unaltered throughout the observation period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613498 TI - Biochemical and autoradiographical determination of protein synthesis in experimental brain tumors of rats. AB - The rate of leucine incorporation into brain proteins was studied in rats with experimental brain tumors produced by intracerebral transplantation of the glioma clone F98. Incorporation was measured with [14C]leucine using a controlled infusion technique for maintaining constant specific activity of [14C]leucine in plasma, followed by quantitative autoradiography and biochemical tissue analysis. After 45 min the specific activity of free [14C]leucine in plasma was 2.5-3 times higher than in brain and brain tumor, indicating that the precursor pool for protein synthesis was fueled both by exogenous (plasma-derived) and endogenous (proteolysis-derived) amino acids. Endogenous recycling of amino acids amounted to 73% of total free leucine pool in brain tumors and to 60-70% in normal brain. Taking endogenous amino acid recycling into account, leucine incorporation was 78.7 +/- 16.0 nmol/g of tissue/min in brain tumor, and 17.2 +/- 4.2 and 9.7 +/- 3.3 nmol/g/min in normal frontal cortex and striatum, respectively. Leucine incorporation within tumor tissue was markedly heterogeneous, depending on the local pattern of tumor proliferation and necrosis. Our results demonstrate that quantitative measurement of leucine incorporation into brain proteins requires estimation of recycling of amino acids derived from proteolysis and, in consequence, biochemical determination of the free amino acid precursor pool in tissue samples. With the present approach such measurements are possible and provide the quantitative basis for the evaluation of therapeutic interventions. PMID- 1613499 TI - Muscarinic receptor stimulated GTPase activity in synaptic membranes from bovine retina. AB - GTPase activity has been measured in synaptic membranes from bovine retina, with and without muscarinic receptor stimulation. Maximal stimulation above basal levels was achieved with 5 microM oxotremorine and 100 microM carbachol. (4 Hydroxy-2-butynyl)-1-trimethylammonium m-chlorocarbanilate chloride, which is selective for the M1 muscarinic receptor, failed to stimulate GTPase activity. 4 Diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) inhibition of oxotremorine stimulation demonstrated the presence of two populations of receptors, a low affinity site (IC50 +/- SEM, 0.63 +/- 0.18 microM) which accounted for 63% of the inhibition and a high-affinity site (IC50 less than 1 nM) which accounted for the remaining 37%. When carbachol-stimulated GTPase activity was assayed, a single 4 DAMP inhibitory site was apparent (IC50 +/- SEM, 2.0 +/- 0.9 microM). Pirenzepine inhibited GTPase activity at a single site (IC50 values +/- SEM, 46.9 +/- 11 and 25.4 +/- 6.5 microM against oxotremorine and carbachol, respectively). Methoctramine was equipotent against carbachol and oxotremorine stimulation (IC50 values, 4.2 +/- 1.8 and 6.2 +/- 1.5 microM). Inhibition of maximal carbachol and oxotremorine stimulation by muscarinic antagonists at the major site had a rank order of potency of 4-DAMP = methoctramine greater than pirenzepine. Thus, the major site for muscarinic stimulation of GTPase activity in bovine retinal membranes is pharmacologically similar to M2 receptors. PMID- 1613500 TI - Effect of intracellular glutamine on the uptake of large neutral amino acids in astrocytes: concentrative Na(+)-independent transport exhibits metastability. AB - To examine whether the concentration gradient of glutamine (Gln) drives concentrative Na(+)-independent uptake of neutral amino acids (NAA) in mouse cerebral astrocytes, uptake was compared in "Gln-depleted" and "Gln-replete" cultures. Uptake (30 min in Na(+)-free buffer) of histidine, kynurenine, leucine, tyrosine, and a model substrate for System L transport was 70-150% greater in Gln replete cultures. Phenylalanine uptake was not affected. All of these NAA trans stimulated the export of Gln from astrocytes. However, the increase in NAA uptake was sustained even though the Gln content of Gln-replete cultures declined. Also, uptake of Gln itself was enhanced in Gln-replete cultures. Thus, countertransport of Gln was insufficient to explain the enhancement of NAA uptake. Enhanced uptake was restored, and could be magnified, by reloading Gln-depleted cultures either with Gln or with histidine. It is suggested that substrate-induced asymmetry and molecular hysteresis in the Na(+)-independent carrier could account for the sustained enhancement of NAA uptake. Only histidine and kynurenine were concentrated comparably to Gln (15- to 29-fold at 1 mM in Na(+)-free buffer). The other NAA were four to six times less concentrated. At least two Na(+)-dependent transport systems also supported the concentration gradient of Gln in regular buffer. PMID- 1613501 TI - Phosphoethanolamine enhances high-affinity choline uptake and acetylcholine synthesis in dissociated cell cultures of the rat septal nucleus. AB - Dissociated rat septal nucleus cells cultured in defined medium exhibited twofold increases in the maximal rates of sodium-dependent, high-affinity choline uptake and acetylcholine formation when grown in the presence of phosphoethanolamine. The effect was concentration-dependent (EC50 = 15 microM) and appeared to be associated with in vitro maturation of cholinergic neurons rather than with enhanced survival. Choline acetyltransferase, acetylcholinesterase, and choline kinase activities were unaffected by this treatment. The effect of phosphoethanolamine was specific for cholinergic neurons, because treatment with this compound did not alter the kinetic constants for high-affinity neuronal uptake of gamma-aminobutyric acid or dopamine. The action appeared to be mediated primarily through activation of the sodium-dependent, high-affinity transport mechanism for choline as opposed to alterations in the storage and release of acetylcholine. PMID- 1613502 TI - Differences in dopamine clearance and diffusion in rat striatum and nucleus accumbens following systemic cocaine administration. AB - Acute cocaine administration preferentially increases extracellular dopamine levels in nucleus accumbens as compared with striatum. To investigate whether a differential effect of cocaine on dopamine uptake could explain this observation, we used in vivo electrochemical recordings in anesthetized rats in conjunction with a paradigm that measures dopamine clearance and diffusion without the confounding effects of release. When a finite amount of dopamine was pressure ejected at 5-min intervals from a micropipette adjacent to the electrode, transient and reproducible increases in dopamine levels were detected. In response to 15 mg/kg of cocaine-HCl (i.p.), these signals increased in nucleus accumbens, indicating significant inhibition of the dopamine transporter. The time course of the dopamine signal increase paralleled that of behavioral changes in unanesthetized rats receiving the same dose of cocaine. In contrast, no change in the dopamine signal was detected in dorsal striatum; however, when the dose of cocaine was increased to 20 mg/kg, enhancement of the dopamine signal occurred in both brain areas. Quantitative autoradiography with [3H]mazindol revealed that the affinity of the dopamine transporter for cocaine was similar in both brain areas but that the density of [3H]mazindol binding sites in nucleus accumbens was 60% lower than in dorsal striatum. Tissue dopamine levels in nucleus accumbens were 44% lower. Our results suggest that a difference in dopamine uptake may explain the greater sensitivity of nucleus accumbens to cocaine as compared with dorsal striatum. Furthermore, this difference may be due to fewer dopamine transporter molecules in nucleus accumbens for cocaine to inhibit, rather than to a higher affinity of the transporter for cocaine. PMID- 1613503 TI - Prohormone thiol protease and enkephalin precursor processing: cleavage at dibasic and monobasic sites. AB - Production of active enkephalin peptides requires proteolytic processing of proenkephalin at dibasic Lys-Arg, Arg-Arg, and Lys-Lys sites, as well as cleavage at a monobasic arginine site. A novel "prohormone thiol protease" (PTP) has been demonstrated to be involved in enkephalin precursor processing. To find if PTP is capable of cleaving all the putative cleavage sites needed for proenkephalin processing, its ability to cleave the dibasic and the monobasic sites within the enkephalin-containing peptides, peptide E and BAM-22P (bovine adrenal medulla docosapeptide), was examined in this study. Cleavage products were separated by HPLC and subjected to microsequencing to determine their identity. PTP cleaved BAM-22P at the Lys-Arg site between the two basic residues. The Arg-Arg site of both peptide E and BAM-22P was cleaved at the NH2-terminal side of the paired basic residues to generate [Met]-enkephalin. Furthermore, the monobasic arginine site was cleaved at its NH2-terminal side by PTP. These findings, together with previous results showing PTP cleavage at the Lys-Lys site of peptide F, demonstrate that PTP possesses the necessary specificity for all the dibasic and monobasic cleavage sites required for proenkephalin processing. In addition, the unique specificity of PTP for cleavage at the NH2-terminal side of arginine at dibasic or monobasic sites distinguishes it from many other putative prohormone processing enzymes, providing further evidence that PTP appears to be a novel prohormone processing enzyme. PMID- 1613504 TI - Nerve growth factor-induced changes in the structure of sulfated proteoglycans in PC12 pheochromocytoma cells. AB - Structural changes in proteoglycans (PGs) were examined during the neuritogenesis of PC12 cells induced by nerve growth factor (NGF). (1) A heparan sulfate (HS) PG and a chondroitin sulfate (CS) PG were synthesized by PC12 cells, irrespective of the presence of NGF or the duration of culture. PGs released from PC12 cells into the culture medium were mostly CSPGs. (2) In the absence of NGF, the apparent molecular mass of HSPG prepared from PC12 cells after 3 days of culture was in the range of 90-190 kDa for the intact form (Kav = 0.38 on Sepharose CL-6B), 12 kDa for HS, and 61 kDa for the core protein. In the presence of NGF, these values were 90-190 kDa, 10 kDa, and 51 kDa and 61 kDa, respectively. The intact forms of cell-associated CSPG had apparent molecular mass ranges of 120-150 kDa and 120 190 kDa (Kav = 0.38 and 0.34), with CSs of 15 kDa and 20 kDa in the presence and absence of NGF, respectively. The apparent molecular mass of the core protein of cell-associated CSPG was 92 kDa, irrespective of the presence of NGF. The molecular sizes of cell-associated PGs and their glycosaminoglycans remained unchanged during culture. (3) CSPGs released by PC12 cells into the culture medium were separated into two peaks (I and II) by column chromatography on DEAE cellulose. The peak II fraction prepared from the medium with NGF after 3 days of culture consisted of CSPG with Kav = 0.22 on Sephacryl S-300 [40-84 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613505 TI - Uptake and distribution of iron and transferrin in the adult rat brain. AB - Brain uptake of iron-59 and iodine-125-labelled transferrin from blood in the adult rat has been investigated using graphical analysis to determine the blood brain barrier permeability to these tracers in experiments that lasted between 5 min and 8 days. The blood-brain barrier permeability (K(in)) to 59Fe was 89 x 10( 5) ml/min/g compared to the value of 7 x 10(-5) ml/min/g for 125I-transferrin, which is similar to that of albumin, a plasma marker. The autoradiographic distribution of these tracers in brain was also studied to determine any regional variation in brain uptake after the tracers had been administered either systemically or applied in vitro. No regional uptake was seen for 125I transferrin even after 24 h of circulation. In contrast, 59Fe showed selective regional uptake by the choroid plexus and extra-blood-brain barrier structures 4 h after administration. After 24 h of circulation, 59Fe distribution in brain was similar to the transferrin receptor distribution, as determined in vitro, but was unlike the distribution of nonhaem iron determined histochemically. The data suggest that brain iron uptake does not involve any significant transcytotic pathway of transferrin-bound iron into brain. It is proposed that the uptake of iron into brain involves the entry of iron-loaded transferrin to the cerebral capillaries, deposition of iron within the endothelial cells, followed by recycling of apotransferrin to the circulation. The deposited iron is then delivered to brain-derived transferrin for extracellular transport within the brain, and subsequently taken up via transferrin receptors on neurones and glia for usage or storage. PMID- 1613506 TI - A novel glial growth inhibitory factor, gliostatin, derived from neurofibroma. AB - Neurofibroma tissue was investigated for the presence of glial growth modulators that would suppress the proliferation of glial cells. A novel endogenous polypeptide inhibitor of proliferation and DNA synthesis in glial cells, gliostatin, was purified from the extracts of neurofibroma by a procedure comprising dye and anion-exchange column chromatography, and HPLC. A monoclonal antibody raised against partially purified gliostatin showed no cross-reactivity with known cytokines, but adsorbed the growth inhibitory activity of gliostatin and immunochemically visualized the putative gliostatin bands on western blot analyses. Although the product showed an apparent M(r) of 100,000 accompanied by an inhibitory activity on gel filtration column chromatography, it migrated at a lower apparent M(r) of 50,000 under the reducing conditions on western blotting, indicating that a homodimeric structure of native gliostatin consisted of 50-kDa subcomponents. Gliostatin was a potent growth inhibitor acting at nanomolar concentrations against all glial tumor cells and glia maturation factor stimulated astroblasts, but not neuronal cells. PMID- 1613507 TI - Changing fatty acid content of growth cone lipids prior to synaptogenesis. AB - The developing mouse was used to assess biochemical changes in membrane lipids during the period when nerve growth cones become synapses. Growth cone particles and synaptosomes were simultaneously obtained from common brain homogenates. Incorporation of the essential fatty acid, docosahexaenoic acid (22:6 omega-3), was correlated with the developmental changes in endogenous fatty acid content of growth cones and synaptosomes. Analysis of endogenous lipid content indicated that, at all ages studied, the growth cones contained more arachidonoyl acyl chains (20:4 omega-6) than did synaptosomes. Before the onset of synaptogenesis, levels of arachidonoyl chains increased and levels of 22:6, oleoyl and linoleoyl chains decreased in synaptosomes. Although stearoyl and palmitoyl (16:0) remained stable in synaptosomes, 16:0 decreased in growth cones. With the exception of 16:0 and 20:4, endogenous fatty acyl content of growth cones and synaptosomes became similar by postnatal day 10, which coincides with the onset of synaptogenesis. When 5-day-old mouse pups were injected intraperitoneally with [3H]22:6, the incorporation into growth cone and synaptosome phospholipids was greatest in phosphatidylethanolamine, followed by phosphatidylserine and phosphatidylcholine. Nominal labeling was present in phosphatidic acid and phosphatidylinositol. Labeling in neutral lipids was less than that of phospholipids, with triacylglycerol incorporating most of the neutral lipid label, followed by diacylglycerol and free 22:6. Only the growth cone fraction contained detectable amounts of 22:6-labeled cholesterol esters. The distribution of 22:6 label in plasma 72 h after injection indicated that approximately 60% of the label was in phospholipids with approximately 40% in neutral lipids and less than 5% in free fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613508 TI - Metabolism of lactate in the rat brain during the early neonatal period. AB - The metabolism of lactate in isolated cells from early neonatal rat brain has been studied. In these circumstances, lactate was mainly oxidized to CO2, although a significant portion was incorporated into lipids (78% sterols, 4% phosphatidylcholine, 2% phosphatidylethanolamine, and 1% phosphatidylserine). The rate of lactate incorporation into CO2 and lipids was higher than those found for glucose and 3-hydroxybutyrate. Lactate strongly inhibited glucose oxidation through the pyruvate dehydrogenase-catalyzed reaction and the tricarboxylic acid cycle while scarcely affecting glucose utilization by the pentose phosphate pathway. Lipogenesis from glucose was strongly inhibited by lactate without relevant changes in the rate of glycerol phosphate synthesis. These results suggest that lactate inhibits glucose utilization at the level of the pyruvate dehydrogenase-catalyzed reaction, which may be a mechanism to spare glucose for glycerol and NADPH synthesis. The effect of 3-hydroxybutyrate inhibiting lactate utilization only at high concentrations of 3-hydroxybutyrate suggests that before ketogenesis becomes active, lactate may be the major fuel for the neonatal brain. (-)-Hydroxycitrate and aminooxyacetate markedly inhibited lipogenesis from lactate, suggesting that the transfer of lactate carbons through the mitochondrial membrane is accomplished by the translocation of both citrate and N acetylaspartate. PMID- 1613509 TI - Extracellular concentrations of dopamine and metabolites in the rat caudate after oral administration of a novel catechol-O-methyltransferase inhibitor Ro 40-7592. AB - The effect of the systemic administration of a novel, orally active, catechol-O methyltransferase (COMT) inhibitor, Ro 40-7592, on the in vivo extracellular concentrations of dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), was studied by transcerebral microdialysis in the dorsal caudate of freely moving rats. Ro 40-7592 (at doses of 3.0, 7.5, and 30 mg/kg p.o.) elicited a marked and long-lasting reduction of HVA, and at doses of 7.5 and 30 mg/kg, an increase of DOPAC output, but it failed to increase DA output. The administration of L-beta-3,4-dihydroxyphenylalanine (L-DOPA, 20 and 50 mg/kg p.o.) with a DOPA decarboxylase inhibitor (benserazide) increased both HVA and DOPAC output, but failed to modify significantly extracellular DA concentrations in dialysates; in contrast, combined administration of L DOPA+benserazide with Ro 40-7592 (30 mg/kg p.o.) resulted in a significant increase in DA output. Ro 40-7592 prevented the L-DOPA-induced increase in HVA output and markedly potentiated the increase in DOPAC output. To investigate to what extent the increase in extracellular DA concentrations was related to an exocitotic release, tetrodotoxin (TTX) sensitivity was tested. Addition of TTX to Ringer, although abolishing DA output in the absence of L-DOPA, partially reduced it in the presence of L-DOPA+Ro 40-7592 and even more so after L-DOPA without the COMT inhibitor. The results of the present study suggest that metabolism through COMT regulates extracellular concentrations of DA formed from exogenously administered L-DOPA but not of endogenous DA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613510 TI - Enhancement by cytidine of membrane phospholipid synthesis. AB - Cytidine, as cytidine 5'-diphosphate choline, is a major precursor in the synthesis of phosphatidylcholine in cell membranes. In the present study, we examined the relationships between extracellular levels of cytidine, the conversion of [14C]choline to [14C]phosphatidylcholine, and the net syntheses of phosphatidylcholine and phosphatidylethanolamine by PC12 cells. The rate at which cytidine (as [3H]cytidine) was incorporated into the PC12 cells followed normal Michaelis-Menten kinetics (Km = 5 microM; Vmax = 12 x 10(-3) mmol/mg of protein/min) when the cytidine concentrations in the medium were below 50 microM; at higher concentrations, intracellular [3H]cytidine nucleotide levels increased linearly. Once inside the cell, cytidine was converted mainly into cytidine triphosphate. In pulse-chase experiments, addition of cytidine to the medium caused a time- and dose-dependent increase (by up to 30%) in the incorporation of [14C]choline into membrane [14C]-phosphatidylcholine. When the PC12 cells were supplemented with both cytidine and choline for 14 h, small but significant elevations (p less than 0.05) were observed in their absolute contents of membrane phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine, all increasing by 10-15% relative to their levels in cells incubated with choline alone. Exogenous cytidine, acting via cytidine triphosphate, can thus affect the synthesis and levels of cell membrane phospholipids. PMID- 1613511 TI - Cell swelling, blebbing, and death are dependent on ATP depletion and independent of calcium during chemical hypoxia in a glial cell line (ROC-1). AB - The morphological and biochemical changes that occur during chemical hypoxic injury in a neural cell line were studied in the presence and absence of calcium. Oligodendroglial-glioma hybrid cells (ROC-1) were subjected to inhibitors of glycolytic and oxidative ATP synthesis (chemical hypoxia). Complete respiratory inhibition depleted [ATP] to less than 5% of control by 4 min. Blebs appeared on the cell surfaces and cells began to swell within a few minutes of ATP depletion. A 200% increase in cell volume and bleb coalescence preceded irreversible cell injury (lactate dehydrogenase release) which began at approximately 20 min with 50% cell death by 40 min. In energized cells an equivalent degree of osmotic swelling induced by ouabain inhibition of the Na+, K(+)-ATPase pump did not produce blebbing or cell death. Partial inhibition of respiration decreased [ATP] to approximately 10% of control by 40 min. Blebbing and swelling began at 40 min and bleb coalescence preceded plasma membrane disruption which began at approximately 55 min. ATP depletion, blebbing, swelling, and death followed similar time courses in the presence or absence of extracellular calcium ([Ca2+]e). Intracellular calcium ([Ca2+]i) was measured using fura-2. In calcium containing medium metabolic inhibition caused a transient increase in resting [Ca2+]i (100 +/- 17 nM) followed by a low steady-state level preceding plasma membrane disruption. Following deenergization in calcium-free medium, [Ca2+]i remained below 60 nM throughout injury and death. These data suggest that decreased ATP initiates a sequence of events including bleb formation and cell swelling that lead to irreversible cell injury in the absence of large increases in [Ca2+]i. PMID- 1613512 TI - Avian brain epinephrine and 5-hydroxytryptamine: is it still a matter of controversy? PMID- 1613513 TI - Specific expression of N-acetylaspartate in neurons, oligodendrocyte-type-2 astrocyte progenitors, and immature oligodendrocytes in vitro. AB - To test the specificity of N-acetylaspartate (NAA) as a neuronal marker for proton nuclear magnetic resonance (1H NMR) spectroscopy, purified and characterized cultured cells were analyzed for their NAA content using both 1H NMR and HPLC. Cell types studied included cerebellar granule neurons, type-1 astrocytes, meningeal cells, oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells, and oligodendrocytes. A high concentration of NAA was found in extracts of cerebellar granule neurons (approximately 12 nmol/mg of protein), whereas NAA remained undetectable in purified type-1 astrocytes, meningeal cells, and mature oligodendrocytes. However, twice the neuronal level of NAA was found in O-2A progenitors grown in vitro. In addition significant levels of NAA were also detected in cultures of immature oligodendrocytes. Our data partly support previous suggestions that NAA may be a useful neuronal marker for 1H NMR spectroscopic examination of the adult brain. However, they also raise the further possibility that alterations of NAA associated with some specific brain disorders, particularly disorders seen in newborn and young children, may reflect abnormalities in the development of oligodendroglia or their precursors. PMID- 1613514 TI - Reduced neuropeptide Y concentrations in suicide brain. AB - Neuropeptide Y (NPY) was measured in postmortem brain tissue from victims of suicide and from individuals dying a sudden natural or accidental death (controls). Concentrations of NPY-immunoreactivity were measured by radioimmunoassay in frontal cortex (BA 10), temporal cortex (BA 22), caudate nucleus, and cerebellum. Concentrations of NPY-immunoreactivity were significantly lower in postmortem frontal cortex (-14%) and caudate nucleus ( 27%) from suicide victims compared with age-matched controls. A subgroup of suicides with evidence of a history of depression revealed more robust reductions in concentrations of NPY-immunoreactivity in frontal cortex and caudate nucleus, as did four individuals who died from natural causes and also were described as having a possible history of depression. Concentrations of NPY-immunoreactivity in temporal cortex and cerebellum from victims of suicide or from the subgroup of subjects with a possible history of depression were not significantly different from those of age-matched controls. We suggest there is a deficit in the brain NPY system leading to region-specific reductions in peptide concentrations in subjects who have a history of depression. PMID- 1613515 TI - Brain-derived neurotrophic factor protects dopamine neurons against 6 hydroxydopamine and N-methyl-4-phenylpyridinium ion toxicity: involvement of the glutathione system. AB - Brain-derived neurotrophic factor (BDNF) has recently been shown to enhance the survival of dopamine neurons in cultures derived from the embryonic rat mesencephalon. We now extend this study by demonstrating that, in addition to the effect of sustaining survival of dopaminergic neurons, BDNF also confers protection against the neurotoxic effects of 6-hydroxydopamine (6-OHDA) and N methyl-4-phenylpyridinium ion (MPP+). Exposure of mesencephalic cultures to either 6-OHDA or MPP+ resulted in a loss of 70-80% of dopaminergic neurons, as determined by tyrosine hydroxylase (TH) immunocytochemistry. In BDNF-treated cultures, loss of TH-positive cells after exposure to either toxin was reduced to only 30%. To facilitate biochemical measurements, we studied SH-SY5Y dopaminergic neuroblastoma cells. BDNF was found to protect these cells from the dopaminergic neurotoxins, 6-OHDA and MPP+. Indicative of oxidative stress, treatment of SH SY5Y cells with 10 microM 6-OHDA for 24 h caused a fivefold increase in the levels of oxidized glutathione (GSSG). Pretreatment with BDNF for 24 h completely prevented the rise in GSSG. Further examination revealed that BDNF increased the activity of the protective enzyme, glutathione reductase, by 100%. In contrast, BDNF had no effect on the activity of catalase. These results add further impetus to exploring the therapeutic potential of BDNF in animal models of Parkinson's disease. PMID- 1613516 TI - Bone graft and total hip arthroplasty. A review. AB - The success of total hip arthroplasty has been well documented. Aseptic loosening remains the major long-term problem that can lead to significant bone loss and structural deficits. Bone graft has been used with increasing frequency to reconstruct these difficult cases. In this review, the authors detail the biology, biomechanics, and banking of bone grafts. A summary of currently available data on the clinical result of autograft and allograft in reconstructive hip surgery is presented. PMID- 1613517 TI - Measurement accuracy in acetabular cup migration. A comparison of four radiologic methods versus roentgen stereophotogrammetric analysis. AB - Four different methods of radiologic evaluation of the acetabular component migration following total hip arthroplasty have been compared with roentgen stereophotogrammetry, a proven highly accurate method for studying early migration. In the Sutherland and Wetherell method the implant's position is measured with a pencil and a ruler from an ordinary pelvis radiograph. New reference lines of the Wetherell method are thought to be more accurate. The Sulzer and EBRA methods are computerized. In the Sulzer method prominent bone markers are digitized and used as reference points. In the EBRA method a system of tangents on prominent pelvis structure is digitized and used to detect radiographs with similar projection. The implant's position is calculated as the mean position of similar radiographs. The Sutherland, Wetherell, and Sulzer methods had almost the same accuracy, whereas the EBRA method was more accurate and could be used for pro- and retrospective studies in a large number of patients. PMID- 1613518 TI - Treatment of fractures about hip prostheses with compression plating. AB - Between 1984 and 1986, 10 patients who sustained a femur fracture about a hip prosthesis were treated with open reduction and internal fixation using compression plating. Nine of the 10 fractures healed in an average time of 5 months. Other than one nonunion, no significant complications were noted. Follow up study, ranging from 13 to 44 months (average, 26 months), was obtained on all 10 patients. One had a loose femoral component, which was attributed to inadequate stem size. None of the other patients had either clinical or radiographic evidence of loosening. Based on Harris hip scores, there was no indication that plating significantly interfered with hip function. The authors believe that these results demonstrate that plating can be an effective method of treating femoral fractures about hip prostheses. PMID- 1613519 TI - Cementless total knee arthroplasty in unselected cases of osteoarthritis and rheumatoid arthritis. A 3-year follow-up study of 103 cases. AB - The authors reviewed 103 cementless AGC 2000 total knee arthroplasties in unselected cases of osteoarthritis and rheumatoid arthritis with a follow-up period of 3 years. Excellent or good clinical results were obtained in 96%. The median maximal flexion was 110 degrees. Two aseptic loosenings of the tibial components had been revised prior to this evaluation. Two other patients showed radiographic signs of tibial loosening but were asymptomatic. Undersizing of the tibial component predisposes to subsidence and loosening. One had septic tibial loosening planned for revision. Four had nonprogressive lucent lines beneath the tibial tray but were asymptomatic. No patellar or femoral component loosening was revealed. Undercorrection of preoperative varus deformity did not dispose to tibial loosening or radiolucency, nor influence the clinical result. In terms of survival of the prosthesis the cumulative success rate was 97.1%. When pain and radiographic loosening was also considered, the success rate was 90.7%. These results encourage uncemented use of this prosthesis, but emphasize the importance of good primary prosthetic fit at the tibial side. PMID- 1613520 TI - Knee arthroplasty rating. AB - A number of rating systems used to evaluate the results of total knee arthroplasty exist. Many of these systems are based on different concepts, and might be expected to give divergent results. To see if this was so, the authors examined a consecutive series of 235 posterior stabilized knee arthroplasties recording the results according to five rating systems: HSS (The Hospital for Special Surgery), Brigham, Freeman, BOA (British Orthopaedic Association), and the VENN diagram. In spite of their apparent differences, all point systems and the BOA gave almost identical results, while the VENN diagram proved to be the most stringent. The authors suggest that any of the current point systems may be used to "score" arthroplasties, but the results should also be rated with the VENN diagram in order to see the quality of the arthroplasty and a comparison between the different series. PMID- 1613521 TI - Dislocation in low-friction arthroplasty. AB - In a series of 2,050 low-friction arthroplasties, 61 cases (2.97%) of dislocation were analyzed. The mechanism of production was malposition of the components (group 1, 33%), deficiency of the abductor mechanism (group 2, 34%), or the association of both (group 3, 26%). Failure to find a cause was even more rare (group 4, 7%). The best treatment is prevention by careful surgical technique, since good results with different procedures have only been attained in 51% of dislocated hips. PMID- 1613522 TI - Pasteurella multocida infection in total knee arthroplasty. Case report and literature review. AB - Pasteurella multocida, a small gram-negative bacterium, is part of the normal mouth flora of many animals, including domestic cats and dogs. While commonly associated with infections in animals, it is a rare cause of human disease. The majority of Pasteurella infections in humans occur with percutaneous inoculation of the organism following a bite by a cat or dog, although disease without antecedent animal exposure or with causal animal contact does occur. The spectrum of disease produced ranges from localized, including abscess, cellulitis, lymphadenopathy, and osteomyelitis, to systemic, with septicemia, septic arthritis, respiratory, and central nervous system involvement. Altered host defenses and underlying chronic disease, such as rheumatoid arthritis, corticosteroid therapy, and severe hepatic or renal disease, may predispose to more serious systemic manifestations of infection. The authors report a case of P. multocida infection in a total knee arthroplasty as a result of a dog scratch and review the literature reporting P. multocida infections in total knee arthroplasty. PMID- 1613523 TI - Subluxation of the posterior stabilized total knee arthroplasty. A report of two cases. AB - There has been only one previous report of dislocation of a posteriorly stabilized total knee arthroplasty. The authors present two further cases of subluxation of this prosthesis and report a method of accomplishing reduction that could not otherwise be achieved by conventional techniques. The current design of this prosthesis enabled revision of the polyethylene tibial component to be undertaken without removal of the cemented metal-backing tray, an advantage not previously appreciated. PMID- 1613524 TI - The effect of polymerization of methylmethacrylate on metal-backed and non-metal backed acetabular components. AB - Aseptic loosening of the acetabular component has been identified as the main cause of failure of cemented total hip arthroplasty in the long term. Wear of the high-density polyethylene has been implicated as a major contributory factor to loosening. The etiology of wear is multifactorial. The exothermic phase of polymerization of polymethylmethacrylate is associated with a 5.9% volume expansion. Using double-exposure holographic interferometry, the authors examined the influence of polymerization of cement on the internal geometry of a metal backed cup and two non-metal-backed cups (Charnley 22 mm, Muller 32 mm). The non metal-backed cups exhibited marked heat concentration points and disrupted fringe patterns, indicating distortion of the internal geometry of the cup. In contradistinction, the metal-backed cup showed good heat dissipation and regular fringe patterns, indicating minimal internal distortion. The differences were not quantified but were visually dramatic. The authors believe this may be an important contributory factor to cup wear in cemented total hip arthroplasty. PMID- 1613525 TI - The effect of extracorporeal shock wave lithotripsy on the prosthesis interface in cementless arthroplasty. Evaluation in a rabbit model. AB - The effect of extracorporeal shock wave lithotripsy on interfacial strength between prosthesis and bone in cementless arthroplasty was examined using a rabbit model. Paired femora, each implanted with fiber mesh porous coated titanium implants, were harvested from rabbits 15 weeks after implantation. In group I, one femur from each pair was exposed to lithotripsy treatment consisting of 2,000 shocks at 20 kV. In group II, one femur from each pair was exposed to 2,000 shocks at 26 kV. Contralateral femora from each pair served as controls in both groups. Mechanical pushout tests were conducted on the implants using a 1321 Instron testing machine at a constant rate of 1 mm/minute. Shock waves generated at 20 kV were found to have no significant decrease on either the prosthesis/bone interfacial strength or energy to failure of cementless implants. Shock waves generated at 26 kV produced a mean 17.45% decrease in the prosthesis/bone interfacial strength, which approached statistical significance (P = .062), and a 7.84% mean decrease in the energy to failure (P = .268). However, in four of the seven group II specimens, cortical fractures occurred. These findings suggest that lithotripsy will not aid in the removal of uncemented porous coated devices and lithotripsy inadvertently focused at an uncemented device will not disrupt significantly the prosthesis-bone interface. PMID- 1613526 TI - A pseudometallosis cyst associated with a Moore prosthesis. A case report. AB - A Moore prosthesis that had been in place for 28 years was revised. Apparent metallosis resulted from contact between the collar and the calcar. A supra acetabular cyst was found packed with black stained debris. Metallurgical examination failed to reveal any metallic debris in the cyst material. This case indicates that all black staining in and of itself is not necessarily indicative of metallosis. PMID- 1613527 TI - Life expectancy after total hip arthroplasty. AB - The 6-year survival rate was investigated in 646 patients undergoing total hip arthroplasty for osteoarthritis, rheumatoid arthritis, or complications following femoral neck fracture between 1978 and 1982. A comparison of mortality was done between patients treated by osteosynthesis for fresh femoral neck fracture and a matched general population. The mortality was lower than that of the matched general population after total hip arthroplasty and even lower for patients treated for fresh femoral neck fracture. Patients undergoing total hip arthroplasty for osteoarthritis had the highest survival rate, followed by patients with rheumatoid arthritis and complications after femoral neck fractures. PMID- 1613528 TI - Diagnosis of deep venous thrombosis by compression ultrasound in knee arthroplasty patients. AB - A prospective study of 62 knee arthroplasty limbs from 60 patients was undertaken to evaluate the effectiveness of compression ultrasound when compared to venography in detecting deep venous thrombosis (DVT). The study was conducted in a double-blind nature. Compression ultrasound and venographic examinations were conducted on the same day within 5-8 days postoperatively. Compression ultrasound had a sensitivity of 85.7%, a specificity of 94.5%, and an accuracy of 93.5% when venography was considered as the gold standard or 100% correct. Positive and negative predictive values were 66.6% and 98.1%, respectively. Eight patients were diagnosed with acute DVT. Five patients presented with calf DVT, one patient had calf DVT extending into the popliteal space, and two patients developed thigh DVT. The authors conclude that compression ultrasound is an efficacious method to evaluate knee arthroplasty patients for deep vein thrombosis. PMID- 1613529 TI - Retained distal femoral osteophyte. An infrequent cause of postoperative pain following total knee arthroplasty. AB - Persistent postoperative pain following total knee arthroplasty is infrequent. This case report describes an unusual cause of pain, crepitus, and effusion following total knee arthroplasty due to a retained distal femoral osteophyte. Osteophyte removal resulted in total alleviation of this patient's discomfort and swelling. PMID- 1613530 TI - Subsidence of porous coated noncemented femoral components in total hip arthroplasty. A roentgen stereophotogrammetric analysis. AB - Roentgen stereophotogrammetric analysis was used in the evaluation of subsidence in nine noncemented femoral components of the Biomet Taperloc prosthesis. After 2 years three components had subsided 0.7-0.9 mm. No distinct symptoms related to the micromotion appeared. The subsidence in this investigation was smaller than the reported subsidence of other noncemented prostheses. PMID- 1613531 TI - Disassembly of the osteonics bipolar ring when used with a Howmedica femoral head. A report of four cases. AB - In 1980 Osteonics marketed their universal head replacement (UHR) as a universal head to fit 32 mm heads. The authors present four cases of ring disassociation in the Osteonics UHR when combined with Howmedica femoral heads. PMID- 1613532 TI - Postoperative blood retrieval and transfusion in cementless total knee arthroplasty. AB - Postoperative wound drainage was aspirated, collected, and transfused in 197 patients undergoing unilateral or bilateral cementless knee arthroplasty using the Solcotrans or the Constavac Blood Conservation blood-retrieval devices. Operative technique, method of hemostasis, and postoperative management were identical in all patients. Drainage-tube suction pressure was minimized, and the duration of drainage collection was less than 8 hours in all patients. In the 153 patients who underwent unilateral total knee arthroplasty (TKA), the amount of blood retrieved and transfused averaged 829 cm3 (59% of total blood lost). For the 44 patients who underwent bilateral procedures, 1,131 cm3 of blood was salvaged (56% of total blood lost). Transfused banked blood averaged 1.7 units (25% homologous) in unilateral cases, while bilateral procedures required 3.0 units (35% homologous). Complications (4%) included wound hematomata in five patients and deep venous thrombosis in two. Transient chills, fever, or tachycardia were seen in four patients at the time of transfusion. Transfusion requirements of banked blood appeared to be significantly reduced, especially in simultaneous bilateral knee arthroplasty, when compared to previous experience in patients who did not undergo postoperative blood retrieval. PMID- 1613533 TI - Angled bearing inserts in total knee arthroplasty. A brief technical note. AB - Malalignment of total knee prosthetic components may lead to premature wear, loosening of components, or patellar instability. Unfortunately, removal of securely cemented or ingrown components is difficult and may be extremely destructive to the available bone stock. Angled bearing inserts provide a means to compensate for malpositioned components and should be considered an alternative to component removal in certain cases. PMID- 1613534 TI - Removal of well-fixed cementless metal-backed patellar components. AB - Removal of well-fixed, cementless metal-backed patellar components can be difficult due to lack of easy surgical access to the anchoring pegs. Five cases of total knee arthroplasty with failed metal-backed cementless patellar components with ingrown anchoring pegs are presented. A technique of removal of these components is described that preserves remaining patellar bone and provides easy access to the well-ingrown anchoring pegs, lessening the risk of fracture during patellar component extraction. PMID- 1613535 TI - The MTT assay for chemosensitivity testing of human tumors of the central nervous system. Part I: Evaluation of test-specific variables. AB - The aim of this study was to optimize the experimental conditions of the MTT assay for primary cultures of human brain tumors. This assay is based on the mitochondrial reduction of MTT-(3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) salt to formazan crystals by living cells. Formazan can be quantified spectrophotometrically. This assay measures the antimetabolic and, by using an adequate recovery period for the cells, also the antiproliferative effects of cytotoxic drugs. Our results suggest the following experimental design for its application as an chemosensitivity assay for human brain tumors: 1-h drug exposure followed by a seven days recovery period without drugs. Then tumor cells are incubated 4 hours with 1 mg MTT/ml and final absorbance readings are performed at 550 nm and 630 nm as test and reference wavelengths respectively. In this way, the assay seems to be a reliable and simple method for rapid chemosensitivity testing in human brain tumors. PMID- 1613536 TI - The MTT assay for chemosensitivity testing of human tumors of the central nervous system. Part II: Evaluation of patient- and drug-specific variables. AB - In this study we assessed the influence of patient- and drug-specific parameters in the short-term MTT-chemosensitivity assay in 150 primary cell cultures derived from human brain tumors. In 45 patients the MTT assay was directly compared with the CFA (Colony Forming Assay). Resistance was 10-20% higher in the MTT assay than in the CFA, but there was a good agreement in both assays, that more malignant gliomas had a higher in vitro chemosensitivity against ACNU and BCNU. Overall the results demonstrate, that there is no uniform correlation between the in vitro chemosensitivity and the histopathological classification of the tumors, which corresponds well to the clinical situation. On the basis of this study we suggest prospective clinical trials with the MTT assay in human brain tumors. PMID- 1613537 TI - Systemic treatment with murine recombinant interleukin-1 beta inhibits the growth and progression of malignant glioma in the rat. AB - We investigated the effects of daily subcutaneous (SC) injections of 100, 200, or 400 micrograms/kg murine recombinant interleukin-1 beta (rIL-1 beta) or its excipient on normal Fischer 344 rats and ones harboring a malignant RT-2 glioma. The tumor model has a predictable course with animals dying on days 14-17 following an intracerebral inoculation of 10(4) RT-2 glioma cells. Treatments with rIL-1 beta or excipient began on day seven post-tumor inoculation and continued for 7 days. We observed no significant effect on core body temperatures although there was a significant (p less than 0.05) decrease in body weight in all rIL-1 beta treated animals. When tumor-bearing animals became moribund, they received an intraperitoneal injection of bromodeoxyuridine (BUdr) and were sacrificed two hours later. Blood samples were obtained prior to their sacrifice by transcardiac perfusion with a buffered aldehyde solution. Recombinant IL-1 beta affected blood differentials; causing neutrophilia, lymphopenia, and slight thrombocythemia. The BUdr labeling index of glioma cells did not significantly differ between treatment groups, although tumors differed histologically at the time of necropsy. Tumors of rIL-1 beta treated animals had more extensive necrosis and a greater degree of leukocyte infiltration. Survival studies were conducted in which rats were given continuous daily SC injections of rIL-1 beta until day of death. Overall survival between the two groups differed significantly in studies using 100 micrograms/kg/d (p less than 0.05); rIL-1 beta treated rats had a mean survival time of 22 (+/- 3.0) days while excipient controls had a mean survival time of 17 (+/- 0.5) days. Similarly, at a dose of 200 micrograms rIL-1 beta/kg/d, mean survival was significantly (p less than 0.05) increased as compared to excipient controls (18.75 +/- 1.5 vs. 15.25 +/- 1.7 days, respectively). Daily injections of 400 micrograms/kg did not significantly increase the survival of glioma bearing animals, possibly as a consequence of rIL-1 beta toxicity at this dose. PMID- 1613538 TI - Primary intraosseous meningioma: case report. AB - A case of 72-year-old Japanese woman with a rare intraosseous meningioma is presented. The tumor was located in the right frontoparietal region, involving the coronal suture. The tumor was excised totally and the pathological diagnosis was meningioma. Similar cases reported in the past literature are reviewed and the possible histogenetic mechanism of the tumor is discussed. PMID- 1613539 TI - Meningitis with Burkitt like B-cell lymphoma in HIV infection. AB - Malignant lymphoma with meningeal involvement was detected in 7 patients with stage IV HIV infection. The diagnosis of lymphoma was made at a maximum of four months before discovery of meningeal involvement. In our seven cases the lymphoma was B-cell type, one case expressed Kappa chains, four cases demonstrated Lambda chains and in two cases differentiation was not possible. A review of findings in all HIV positive patients treated in the same period revealed 10 non-Hodgkin lymphomas of the B-cell type, though meningeal and cerebral involvement was observed only in B-cell lymphoma of the Burkitt type. PMID- 1613540 TI - Diagnosis and treatment of patients with meningeal carcinomatosis. AB - The records of thirty-four patients with meningeal carcinomatosis treated at our hospital between 1984 and 1990 were reviewed. The sources, histologies, metastatic lesions outside the central nervous system, the history of the treatment of primary lesions and intraparenchymal of metastatic brain tumors and the period from the diagnosis of primary lesions and the treatment of intraparenchymal metastatic brain tumors to the diagnosis of meningeal carcinomatosis were investigated. Meningeal carcinomatosis was diagnosed and by neurological signs, CSF cytology, CT scan and MRI. Each patient was given a 5 mg single dose of methotrexate (MTX) alone or combined with 20 mg cytosine arabinoside (Ara-C) administered by intrathecal injection via an Ommaya reservoir and standard lumbar puncture with or without radiotherapy. Following intrathecal chemotherapy 22 of 29 patients showed symptomatic improvement of meningeal irritation and in 10 of 29 patients with cranial nerve impairment amelioration of symptoms was also observed. Moreover, CSF cytology became negative in 10 of 29 patients after a full course of intrathecal chemotherapy. Neurotoxicity Leukoencephalopathy, a neurotoxic effect of intrathecal chemotherapy was not observed in any of the patients. From these results, MTX in small doses is recommended for intrathecal chemotherapy of meningeal carcinomatosis to prevent neurotoxicity. PMID- 1613542 TI - Disparity sensitivity of neurons in monkey extrastriate area MST. AB - We tested the disparity sensitivity of neurons from the medial superior temporal area (MST) in awake behaving monkeys. While the monkey looked at a fixation spot on a screen in front of it, random dot stimuli moved in the preferred direction of the cell under study, and the disparity of the dots made the stimuli appear to move in a frontoparallel plane in front of, on, or behind the screen. Over 90% of the 272 neurons studied were sensitive to the disparity of the visual stimulus. Of those disparity-sensitive cells, 95% were most responsive either to near stimuli (stimuli with crossed disparities appearing to move in front of the screen) or to far stimuli (stimuli with uncrossed disparities appearing to move behind the screen). In a smaller sample of the disparity-sensitive cells, we found cells whose preferred direction of stimulus motion reversed as the disparity of the stimulus reversed. For example, a cell that responded best to rightward motion for near stimuli responded best to leftward motion for far stimuli. We found that 40% of the disparity-sensitive cells had this disparity dependent direction selectivity. This disparity-dependent direction selectivity was maintained over the entire range of speeds tested (6-56 degrees/sec). We tested whether the disparity sensitivity of the neurons indicated the distance of the stimulus from the screen where the monkey was fixating (relative depth) or the distance of the stimulus from the monkey (absolute depth) by having the monkey fixate at different depths in front of or behind the screen. For most MST neurons, the changes in vergence did not alter the disparity response, indicating that the disparity sensitivity of these neurons conveyed information on depth relative to the plane of fixation. We conclude that the disparity characteristics of cells in the dorsomedial MST are those expected of a system serving primarily coarse rather than fine stereopsis. The correlation between disparity selectivity and direction selectivity in these neurons, as well as their other properties, suggests a role in signaling the direction of self-motion of the observer through the environment. PMID- 1613541 TI - Cerebral infection complicating systemic aspergillosis in acute leukemia: clinical and radiographic presentation. AB - Cerebral fungal infection is becoming an increasingly recognized entity in immunocompromised patients on post-mortem examination. In order to determine the frequency of clinically significant cerebral fungal infection and define its clinical characteristics in a cohort of immunocompromised patients at high risk of fungal infection, the records of 118 patients with acute leukemia were examined for 57 clinical and laboratory features. The characteristics of 26 patients with systemic aspergillosis and acute leukemia were compared to 92 patients with acute leukemia in a control group. Eight of 118 patients (7%) had cerebral infection (seven Aspergillus, on Candida). Patients with systemic aspergillosis were more likely than patients in the control group to have focal neurologic findings (p = 0.02), confusion (p = 0.04), and abnormal computerized tomography (CT) of the brain characterized by single or multiple, enhancing or non-enhancing hypodense lesions (p = 0.02). Patients with systemic aspergillosis were more likely to die in complete remission than patients in the control group (p = 0.003); three of six patients with aspergillosis who died in remission expired as a consequence of cerebral infection. Cerebral infection complicated systemic Aspergillus infection in seven of 26 patients (27%), versus one of 16 patients with systemic Candida infection (6%) (p = NS). The authors conclude, therefore, that systemic aspergillosis complicating acute leukemia is more likely to be associated with confusion, focal neurologic findings, and abnormal CT scan of the brain, and that these findings suggest the presence of cerebral infection. In addition, cerebral infection commonly complicates the course of systemic aspergillosis, and is a significant cause of morbidity and mortality in patients with acute leukemia. A high index of suspicion is needed to insure early diagnosis and appropriate therapy, particularly in those who achieve remission of their leukemia. PMID- 1613543 TI - Sensory tuning beyond the sensory system: an initial analysis of auditory response properties of neurons in the lateral amygdaloid nucleus and overlying areas of the striatum. AB - The lateral amygdaloid nucleus (AL) is anatomically connected with sensory processing structures in the thalamus and cortex and is believed to be critically involved in emotional processing by virtue of these connections. In order to understand further how auditory projections to AL contribute to emotional processing, acoustic response properties of single AL neurons were characterized in rats. Recordings were also made in the posterior striatum dorsal to AL. Many cells in AL and the striatum could be driven by broad-band auditory stimulation with white noise or clicks. Initial onset latencies were typically between 12 and 25 msec. Most cells also had later responses (60-150 msec), and a few only had late responses. In frequency receptive field tests, different classes of cells were identified. One group had relatively clear frequency preferences. Thresholds for these relatively tuned cells tended to be somewhat higher in AL than in the striatum. Frequency preferences for AL cells were always above 10 kHz. Although most striatal cells had preferences for frequencies above 10 kHz, some cells were found with frequencies below 10 kHz as well. A second group of acoustically responsive neurons, much more common in AL than in the striatum, showed no frequency specificity (untuned cells). These responded to a wide range of frequencies, even at intensities near threshold. A third group, found mainly in AL (approximately 60% of the total population of cells examined in AL), exhibited rapid habituation to auditory stimuli. These tended to have high thresholds (80 100 dB). Because these cells habituated so quickly, frequency specificity could not be determined. Responses in AL and the striatum were compared with responses in the "specific" auditory relay nucleus of the thalamus, the ventral division of the medial geniculate body, where cells had shorter onset latencies, narrower tuning functions, and lower-intensity thresholds than cells in AL and striatal areas. These findings show that cells in AL exhibit a wide range of auditory tuning properties and suggest that information processing in the amygdala might be fruitfully studied as a direct extension of processing in sensory afferent structures. PMID- 1613544 TI - A nonphotic stimulus causes instantaneous phase advances of the light-entrainable circadian oscillator of the Syrian hamster but does not induce the expression of c-fos in the suprachiasmatic nuclei. AB - The study investigated whether nonphotic cues that alter the phase of overt circadian rhythms do so by causing instantaneous shifts in the underlying, light sensitive clock. Wheel-running activity in Syrian hamsters was studied under free running conditions of constant dim red light as an overt marker of circadian phase, the daily onset of activity being defined as circadian time 12 (CT 12). Exposure to a 15 min pulse of bright light at CT 12.20 caused a phase delay in activity onset, whereas pulses delivered at CT 11.20 had no effect upon the overt rhythm. Correlated with their effect on behavior, light pulses delivered at CT 12.20 induced expression of c-fos-like immunoreactivity in the retinorecipient regions of the suprachiasmatic nuclei of the hypothalamus (SCN), whereas pulses delivered at CT 11.20 had no effect upon the expression of c-fos. Expression of this immediate-early gene therefore provided a second marker of circadian phase, because its induction by light is closely correlated with the onset of subjective night (CT 12). To establish a suitable protocol for nonphotic shifts of the activity rhythm, animals were handled and received a subcutaneous injection of saline at different circadian phases. Injections at CT 8 or CT10 caused an immediate bout of wheel-running activity, and a consequent phase advance in the activity rhythm as assessed by the earlier onsets of activity in successive days. Handling and injections at other circadian phases were without effect. Despite shifting the overt rhythm, these procedures at CT 10 did not lead to the expression of c-fos in the SCN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613545 TI - In vitro neurogenesis by neuronal precursor cells derived from the adult songbird brain. AB - The vocal control nucleus of the adult songbird forebrain, HVc, exhibits de novo neurogenesis in adulthood, with the production of new neurons from precursor cells located in the overlying ventricular zone (Goldman and Nottebohm, 1983). We previously established that explants derived from neurogenic regions of the adult canary forebrain could be maintained in vitro, under conditions that permitted the migration and differentiation of those new neurons previously generated in vivo (Goldman, 1990). However, we found no evidence for continued neuronal mitogenesis in these cultures, which were raised in high concentrations of serum. In the present study, we investigated the permissive conditions for in vitro neurogenesis by these adult forebrain-derived ventricular zone explants. When HVc explants derived from adult zebra finches were maintained in low-serum medium, in vitro neurogenesis could be demonstrated by 3H-thymidine uptake as long as 5 days after explantation. Immunocytochemistry for microtubule-associated protein-2 followed by autoradiography confirmed the neuronal identity of these 3H-thymidine incorporating cells. In vitro neuronal production occurred in an inverse relation to the serum concentration: Over the range of 2.5-25% fetal bovine serum, neuronal 3H-thymidine labeling was most frequent in those cultures exposed to the lowest serum levels. This facilitation of in vitro neuronal mitogenesis by serum depletion suggests that fetal serum may contain factors that inhibit the division of adult-derived neuronal precursor cells, either directly or by agents released by serum-stimulated glial or ependymal cells. PMID- 1613546 TI - Functional anatomy of human procedural learning determined with regional cerebral blood flow and PET. AB - The functional anatomy of motor skill acquisition was investigated in six normal human subjects who learned to perform a pursuit rotor task with their dominant right hand during serial positron emission tomography (PET) imaging of relative cerebral blood flow (relCBF). The effect of motor execution, rather than learning, was identified by a comparison of four motor performance scans with two control scans (eye movements only). Motor execution was associated with activation of a distributed network involving cortical, striatonigral, and cerebellar sites. Second, the effect of early motor learning was examined. Performance improved from 17% to 66% mean time on target across the four PET scans obtained during pursuit rotor performance. Across the same scans, significant longitudinal increases of relCBF were located in the left primary motor cortex, the left supplementary motor area, and the left pulvinar thalamus. The results demonstrate that changes of regional cerebral activity associated with early learning of skilled movements occur in sites that are a subset of a more widely distributed network that is active during motor execution. PMID- 1613547 TI - Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat. AB - We have found that the density of synapses in the stratum radiatum of the hippocampal CA1 region in the adult female rat is sensitive to estradiol manipulation and fluctuates naturally as the levels of ovarian steroids vary during the 5 d estrous cycle. In both cases, low levels of estradiol are correlated with lower synapse density, while high estradiol levels are correlated with a higher density of synapses. These synaptic changes occur very rapidly in that within approximately 24 hr between the proestrus and estrus stages of the estrous cycle, we observe a 32% decrease in the density of hippocampal synapses. Synapse density then appears to cycle back to proestrus values over a period of several days. To our knowledge, this is the first demonstration of such short term steroid-mediated synaptic plasticity occurring naturally in the adult mammalian brain. PMID- 1613548 TI - Gene regulation in an ascending nociceptive pathway: inflammation-induced increase in preprotachykinin mRNA in rat lamina I spinal projection neurons. AB - Tachykinin peptides are distributed widely in the nervous system and have been shown to play a prominent role in nociceptive pathways in the spinal cord and dorsal root ganglia. This study investigated the inflammation-induced response of dorsal horn projection neurons and local circuit neurons expressing preprotachykinin (PPT) mRNA using RNA blot analysis and in situ hybridization histochemistry. To identify projection neurons, fluorogold was injected into the parabrachial area of the brainstem. In laminae I, II and V/VI ipsilateral to inflammation, there was a differential increase in the number of neurons exhibiting PPT mRNA. In lamina I, the number of spinal projection neurons containing PPT mRNA showed a greater than 200% increase. The identification of spinal projection neurons with inflammation-induced increases in PPT mRNA suggests that tachykinin peptides may act as neurotransmitters in nociceptive CNS projection pathways. PMID- 1613549 TI - Enduring memory impairment in monkeys after ischemic damage to the hippocampus. AB - Patient RB became amnesic following an episode of global ischemia that resulted in a bilateral lesion of the CA1 field of the hippocampus. This finding suggested that damage restricted to the hippocampus is sufficient to produce clinically significant memory impairment. To evaluate further the effect of ischemic brain damage on memory, we have developed an animal model of cerebral ischemia in the monkey. Monkeys were subjected to 15 min of reversible ischemia, using a noninvasive technique involving carotid occlusion and pharmacologically induced hypotension. These monkeys sustained significant loss of pyramidal cells in the CA1 and CA2 fields of the hippocampus, as well as loss of somatostatin immunoreactive cells in the hilar region of the dentate gyrus. Cell loss occurred bilaterally throughout the rostrocaudal extent of the hippocampus but was greater in the caudal portion. Except for patchy loss of cerebellar Purkinje cells, significant damage was not detected in areas outside the hippocampus, including adjacent cortical regions, that is, entorhinal, perirhinal, and parahippocampal cortex, and other regions that have been implicated in memory function. On behavioral tests, the ischemic monkeys exhibited significant and enduring memory impairment. On the delayed nonmatching to sample task, the ischemic monkeys were as impaired as monkeys with lesions of the hippocampal formation and adjacent parahippocampal cortex (the H+ lesion). On two other memory tasks, the ischemic monkeys were less impaired than monkeys with the H+ lesion. In neuropathological evaluations, it has always been difficult to rule out the possibility that significant areas of neuronal dysfunction have gone undetected. The finding that ischemic lesions produced overall less memory impairment than H+ lesions indicates that the ischemic monkeys (and by extension, patient RB) are unlikely to have widespread neuronal dysfunction affecting memory that was undetected by histological examination. These results provide additional evidence that the hippocampus is a focal site of pathological change in cerebral ischemia, and that damage limited to the hippocampus is sufficient to impair memory. PMID- 1613550 TI - A cell-surface heparan sulfate proteoglycan mediates neural cell adhesion and spreading on a defined sequence from the C-terminal cell and heparin binding domain of fibronectin, FN-C/H II. AB - FN-C/H II is a heparin binding synthetic peptide from the C-terminal cell and heparin binding domain of fibronectin (FN) that mediates neuronal cell adhesion, spreading, and neurite outgrowth. Cellular interactions with FN-C/H II are inhibited by soluble heparin, suggesting that a cell-surface proteoglycan may mediate interactions with FN-C/H II (Haugen et al., 1990). To test this hypothesis further, heparan sulfate (HS) or chondroitin sulfate (CS) was removed from the cell surface by enzyme treatment. Heparitinase but not chondroitinase treatment of cells inhibited rat B104 neuroblastoma cell adhesion and spreading on FN-C/H II. Additionally, heparitinase treatment decreased the spreading of cells on the 33/66 kDa fragments containing the C-terminal heparin binding domain of FN. Furthermore, antibodies generated against a mouse melanoma HS proteoglycan (HSPG) inhibited B104 cell adhesion to FN-C/H II and the 33/66 kDa FN fragments. 35S-HSPG isolated from B104 cells directly bound to FN-C/H II both in solid phase assays and by affinity chromatography, but failed to bind to a control peptide from this region, CS1. The binding of 35S-HSPG was predominantly mediated by the HS and not the core protein of the HSPG. SDS-PAGE of iodinated HSPG demonstrated a single 78 kDa core protein following heparitinase digestion, which migrated at 51 kDa under nonreducing conditions. Anti-HSPG antibodies recognized the 78 kDa core protein by immunoblotting, and stained the surface of rat B104 neuroblastoma cells and cells of the primary neonatal rat nervous system. These results identify a cell-surface HSPG that likely mediates neuronal cell binding interactions with FN-C/H II. PMID- 1613551 TI - Dynamic regulation of NGFI-A (zif268, egr1) gene expression in the striatum. AB - The expression of immediate-early genes of the fos/jun leucine zipper family can be regulated in striatal neurons by stimuli affecting the dopaminergic nigrostriatal system. The regulatory effects are gene specific, region specific, and striatal compartment specific. In the experiments reported here, we have explored the possibility that dopaminergic stimulation might also affect striatal expression of NGFI-A, a member of the zinc finger family of immediate-early genes. We treated healthy adult rats with amphetamine or cocaine and monitored the acute response of striatal neurons by in situ hybridization with oligonucleotide probes for NGFI-A mRNA. Both drugs evoked rapid, anatomically patterned increases in NGFI-A mRNA expression in the dorsal striatum (caudoputamen) and in the ventral striatum (nucleus accumbens, olfactory tubercle). The main response to each drug was in medium-sized neurons, known to be the projection neurons of the striatum. At every dose of amphetamine eliciting a response, the increased NGFI-A mRNA expression was preferentially concentrated in striosomes of the rostral caudoputamen, whereas cocaine at each dose given induced expression of NGFI-A mRNA in both striosomes and matrix at these striatal levels. The two indirect agonists evoked NGFI-A expression in both striatal compartments farther caudally, especially in the central and medial caudoputamen. Activation by both drugs was blocked by pretreatment with the D1-selective dopamine receptor antagonist SCH23390. These patterns of NGFI-A activation are remarkably similar to those found for Fos-like immunoreactivity following acute amphetamine and cocaine treatments, suggesting that coordinate activation of members of at least two immediate-early gene families occurs in the striatum following catecholaminergic stimulation. Such patterns of induction strongly support the view that the genomic responsiveness of the striosome and of the matrix compartments of the rostral striatum are distinct at the level of early response gene expression. These findings raise the interesting possibility that some of the well-known effects of dopaminergic stimulation on neuropeptide and neurotransmitter expression in the striatum may reflect particular combinatorial patterns of immediate-early gene activation. PMID- 1613552 TI - Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: implications for the maturation of synaptic physiology and long-term potentiation. AB - It has long been hypothesized that changes in dendritic spine structure may modify the physiological properties of synapses located on them. Due to their small size, large number, and highly variable shapes, standard light microscopy of Golgi impregnations and electron microscopy (EM) of single thin sections have not proved adequate to identify most spines in a sample or to quantify their structural dimensions and composition. Here we describe a new approach, the series sample, that was developed to classify by shape and subcellular composition all of the spines and synapses in a sample of neuropil by viewing them through serial EM sections. Spines in each class are then randomly selected for serial reconstruction and measurement in three dimensions. This approach was used to assess whether structural changes in hippocampal CA1 spines could contribute to the enhanced synaptic transmission and the greater endurance of long-term potentiation (LTP) that occur with maturation. Our results show a near doubling in the total density of synapses in the neuropil and along reconstructed dendrites between postnatal day 15 (PND 15) and adult ages. However, this doubling does not occur uniformly across all spine and synapse morphologies. Thin spines, mushroom spines containing perforated postsynaptic densities (PSDs) and spine apparatuses, and branched spines increase by about four-fold in density between PND 15 and adult ages. In contrast, stubby spines decrease by more than half and no change occurs in mushroom spines with macular PSDs or in dendritic shaft synapses. The stubby spines that remain are smaller in adults than at PND 15 and the mushroom spines are larger, while no change occurs in the three dimensional structure of thin spines. Only a few spine necks at either age are constricted or long enough to attenuate charge transfer; therefore, the doubling in synapses should mediate the enhancement of synaptic transmission that occurs with maturation. In addition, LTP is not likely to be mediated by widening of spine necks at either age. However, the constricted spine necks could serve to concentrate specific molecules at activated synapses, thereby enhancing the specificity and endurance of LTP with maturation. These results demonstrate that the new series sample method combined with three-dimensional reconstruction reveals quantitative changes in the frequency and structure of spines and synapses that are not discernable by other methods and are likely to have dramatic effects on synaptic physiology and plasticity. PMID- 1613553 TI - Presynaptic control of modulatory fibers by their neural network targets. AB - Numerous modulatory fibers control the output of the pyloric and gastric mill neural networks in the crustacean stomatogastric ganglion (STG). We now describe the first results of intracellular recordings from the axon of one of these input neurons, stomatogastric nerve axon 1 (SNAX 1), close to where it enters the STG. SNAX 1 excites both the pyloric and gastric mill rhythms and is identified on the basis of its synaptic interactions with identified STG neurons. SNAX 1 receives synaptic input from several sources within the STG. As a result of these synaptic inputs, SNAX 1 fires bursts of action potentials that are time-locked to both the pyloric and gastric mill rhythms. The synaptic connections made onto the SNAX axon terminals are likely to play important roles in shaping the impulse activity patterns in these modulatory inputs. Thus, the fibers that modulate the pattern generating networks in the STG are themselves influenced by elements in these networks, and modulation is a dynamic interaction between input fibers and STG neurons. PMID- 1613554 TI - Prostaglandin E2 exerts an awaking effect in the posterior hypothalamus at a site distinct from that mediating its febrile action in the anterior hypothalamus. AB - The precise sites for prostaglandin E2 (PGE2)-related activity responsible for the promotion of wakefulness and elevation of brain temperature were determined in several regions of the monkey brain. PGE2 was administered through a microdialysis probe into 11 brain loci mainly in the preoptic area/anterior hypothalamic region (POA/AH) and the tuberomammillary region in the posterior hypothalamus (TuM-PH). Administration of PGE2 into the POA/AH resulted in a marked and dose-dependent febrile response. When a low dose (15 pmol/min) of PGE2 was administered into the POA/AH, brain temperature increased significantly up to a 0.6 degrees C rise, but sleep behavior and amounts of time in wakefulness, slow wave sleep (SWS), and REM sleep during the administration period were not significantly different from those of the control monkeys. Dose of PGE2 above 150 pmol/min elevated the brain temperature and heart rate more markedly and suppressed sleep. The degree of inhibition of sleep by PGE2 was closely correlated with the changes in these autonomic responses. On the other hand, when a low dose of PGE2 was administered into the TuM-PH, the time spent awake during the administration period increased up to 3.5-fold and the amount of time spent in SWS decreased to 50% of that of the control level, with negligible changes in brain temperature and heart rate. The awaking response of PGE2 in the TuM-PH was also dose dependent, but was not correlated with the change in brain temperature. Among 11 brain regions tested, the hyperthermic effect of PGE2 was most potent in the POA, while its awaking effect was most pronounced in the TuM-PH close to the mammillary complex. These findings demonstrate that the site of action of PGE2 for the regulation of sleep-wakefulness is clearly distinct from that for the temperature regulation. PGE2 may be involved in the neurochemical mechanism of wakefulness mediated in a specific site in the PH. PMID- 1613555 TI - The period gene encodes a predominantly nuclear protein in adult Drosophila. AB - The period gene of Drosophila melanogaster (per) is important for the generation and maintenance of biological rhythms. Previous light microscopic observations indicated that per is expressed in a variety of tissues and cell types and suggested that the per protein (PER) may be present in different subcellular compartments. To understand how PER influences circadian rhythms, it is important to define its subcellular location, especially in adult flies where inducible promoter experiments suggested that it is most relevant to circadian locomotor activity rhythms. To this end, we report the results of an immunoelectron microscopic analysis of wild-type flies and per-beta-galactosidase (beta-gal) fusion gene transgenics using a polyclonal anti-PER antibody or an anti-beta-gal antibody, respectively. Most of the PER antigen and the fusion gene product were located within nuclei, suggesting that PER acts in that subcellular compartment to affect circadian rhythms. The results are discussed in terms of per's possible biochemical functions. PMID- 1613556 TI - Astrocyte precursors in neonatal rat spinal cord cultures. AB - Cultures of newborn rat spinal cord contain multiple types of astrocytes. By using a combination of cultures enriched for glial precursors and clonal analysis, we have identified a particular astrocyte precursor that gives rise to morphologically distinct classes of astrocytes. This astrocyte precursor labels with the monoclonal antibody A2B5, is highly migratory, proliferates in response to serum and platelet-derived growth factor, and differentiates into process bearing astrocytes, many of which subsequently assume a "pancake"-shaped morphology. A2B5+ astrocyte precursors share antigenic and migratory characteristics with previously described O2A progenitor cells but differ in their response to regulatory factors, including serum and coculture with type 1 astrocytes. More importantly, these astrocyte precursors do not give rise to oligodendrocytes. In their proliferative response to serum and their capacity to differentiate into astrocytes, these glial precursors resemble type 1 astrocyte precursors from optic nerve. However, unlike type 1 astrocyte precursors, these cells are A2B5+, highly migratory, and do not give rise to fibroblast-like astrocytes. Neonatal rat spinal cord cultures contain approximately twice the number of the A2B5+ astrocyte precursors than O2A progenitor cells. By contrast, the majority of A2B5+ cells in postnatal day 7 optic nerve cultures are O2A progenitors. The presence of large numbers of A2B5+ astrocyte precursors in rat spinal cord cultures may reflect the more complex cytoarchitecture of the spinal cord compared to the optic nerve. PMID- 1613557 TI - Nicotine binding and nicotinic receptor subunit RNA after chronic nicotine treatment. AB - DBA mice were chronically treated with nicotine by continuous intravenous infusion of 4.0 mg/kg/hr for 10 d. Drug-treated mice were tolerant to the acute effects of nicotine on locomotor activity and body temperature. The effect of chronic treatment on the amount of L-3H-nicotine binding and RNA encoding for alpha 4, the most widely expressed nicotinic alpha-subunit, was measured in three brain regions. Chronic treatment increased L-3H-nicotine binding in cortex and midbrain but had no effect in cerebellum. In contrast, chronic treatment had no effect on the levels of mRNA encoding for alpha 4 in any of the three brain regions. Subsequently brains were sectioned and L-3H-nicotine binding was measured using quantitative autoradiographic methods. In addition, the relative amounts of mRNA for the major nicotinic receptor subunits (alpha 4 and beta 2), as well as for three additional minor subunits (alpha 2, alpha 3, and alpha 5), were determined by in situ hybridization histochemistry followed by quantitation of image intensity. Chronic nicotine treatment resulted in increases in the amount of L-3H-nicotine binding in many but not all brain areas measured. In contrast, chronic treatment had little effect on the intensity of the hybridization signal for the nicotinic subunit mRNA. The results suggest that chronic treatment with nicotine under conditions resulting in maximal steady state increases in L-3H-nicotine binding has little effect on RNA levels encoding any of four nicotinic alpha-subunits and the beta 2-subunit. PMID- 1613558 TI - Multiple axonal spike initiation zones in a motor neuron: serotonin activation. AB - The lateral gastric (LG) motor neuron of the stomatogastric nervous system of the crab Cancer borealis has a large soma in the stomatogastric ganglion (STG). The LG motor neuron makes inhibitory synaptic connections within the neuropil of the STG, and also projects to the periphery, where it innervates a series of muscles that control the movements of the lateral teeth of the gastric mill. The LG motor neuron has a spike initiation zone close to its neuropilar integrative regions, from which spikes propagate orthodromically to the muscles. Additionally, under certain conditions, the LG neuron can initiate spikes at peripheral axonal sites that can be 0.5-2.0 cm from the STG. Peripherally initiated spikes propagate antidromically into the STG and also propagate to the muscle. The peripheral spike initiation zones are often active in combined preparations in which the muscles are left attached. When the muscles are removed, depolarization of the LG soma together with 5-HT applied to the motor nerve also evokes peripheral spike initiation. At a given 5-HT concentration, the duration of the trains of antidromic spikes can be controlled by current injection into the soma, suggesting the presence of a slow voltage-dependent conductance in the LG axon. The antidromic spikes contribute to lengthening of the duration of contraction in some of the muscles innervated by the LG, but do not evoke IPSPs onto LG follower neurons. Thus, the LG neuron can send different signals to its peripheral and central targets. PMID- 1613559 TI - Spontaneous locomotor hyperactivity in a mouse mutant with a deletion including the Snap gene on chromosome 2. AB - The gene encoding the synaptosomal-associated protein--25 kDa (SNAP-25) was mapped by analysis of somatic cell hybrids and an intersubspecies backcross to mouse Chromosome 2. To identify potential mutants for SNAP-25, mice bearing mutations mapping to this region of Chromosome 2 were screened for Snap gene abnormalities. Mice heterozygous for the semidominant mutation coloboma (Cm/+) were identified that carried a deletion of Snap gene sequence. Analysis of genomic DNA revealed that the Snap gene dosage in Cm/+ mice was 50% lower than control littermates. Additionally, SNAP-25 mRNA and protein expression were 50% lower in coloboma mice than control littermates. The coloboma mouse phenotype is characterized by small eyes and head bobbing; in addition, we observed that these mice were extremely hyperactive with spontaneous locomotor activity exceeding three times control mouse activity. The localization of the genetic abnormality in coloboma mice using the Snap gene marker will provide a powerful tool for studying the biologic basis of locomotor hyperactivity. PMID- 1613560 TI - Rapid development of dopaminergic supersensitivity in reserpine-treated rats demonstrated with 14C-2-deoxyglucose autoradiography. AB - Dopaminergic denervation supersensitivity has been implicated in the pathogenesis of levodopa-induced dyskinesias, the most common and limiting side effect in the drug treatment of Parkinson's disease, yet the mechanisms that mediate altered drug sensitivity remain poorly understood. In animals models, one key component of denervation supersensitivity is the enhanced efficacy of selective D1 agonists to stimulate locomotion. In rats with chronic dopamine depletion induced by 6 hydroxydopamine nigral lesion, the increased ability of D1 agonists to stimulate regional cerebral glucose utilization (RCGU) in the substantia nigra pars reticulata (SNr) has provided a metabolic correlate to the heightened motor response. In this study, we used the stimulation of RCGU in the SNr as a sensitive in vivo assay of D1 agonist effect to examine the time course of development of supersensitivity in rats following acute dopamine depletion with single doses of reserpine (5.0 mg/kg, i.p.) and alpha-methyl-p-tyrosine (AMPT; 100 mg/kg, i.p.). The stimulatory effect of the D1 agonist SKF 38393 (30 mg/kg) on RCGU in the SNr was first enhanced 6 hr after reserpine/AMPT injection and was maximally enhanced at 12-24 hr (relative 2-deoxyglucose uptake increased 32-51%; P less than 0.05). The response to SKF 38393 returned to control values 5 d after reserpine/AMPT injection. The single reserpine/AMPT injections depleted striatal dopamine to 1-2% of control values from 3-48 hr postinjection, whereas D1 and D2 dopamine receptor densities were unchanged at 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613561 TI - Euglycemic hyperinsulinemic clamp and oral glucose load in stimulating myocardial glucose utilization during positron emission tomography. AB - To enable assessment of myocardial viability, myocardial glucose utilization has commonly been stimulated by oral glucose loading. To compare the effects of glucose loading and insulin and glucose infusion (insulin clamp) on PET fluorodeoxyglucose ([18F]FDG) myocardial scan image quality and regional myocardial glucose utilization rate (rMGU), eight patients with angiographically documented coronary artery disease and previous myocardial Q-wave infarction were studied twice, once during insulin clamp and once 1 hr after oral glucose loading. The rMGU rates were derived by graphic Patlak analysis in 33 normal, 10 scar and 6 "hot spot" myocardial segments. Infusion of insulin and glucose gave stable plasma-glucose and serum-insulin levels during imaging. In contrast, glucose loading caused marked changes in plasma-glucose and insulin concentrations. The image quality was clearly superior and the fractional utilization rates of [18F]FDG were twice as high during insulin clamp than after glucose loading (p less than 0.0001). Due to the higher plasma-glucose levels after glucose loading, the calculated rMGU in normal, scar and hot spot myocardial segments was comparable between the two protocols. The insulin clamp technique makes it possible to adjust and maintain a metabolic steady state during the PET study. It does not alter [18F]FDG uptake patterns in different myocardial areas when compared to the standard glucose loading protocol, but this technique results in superior image quality and permits the use of smaller [18F] FDG patient doses. PMID- 1613562 TI - Euglycemic hyperinsulinemic clamp and oral glucose load in stimulating myocardial glucose utilization during positron emission tomography. PMID- 1613563 TI - Myocardial FDG PET studies with the fasting, oral glucose-loading or insulin clamp methods. PMID- 1613564 TI - Metabolic cardiac imaging in severe coronary disease: assessment of viability with iodine-123-iodophenylpentadecanoic acid and multicrystal gamma camera, and correlation with biopsy. AB - Fifteen patients with coronary disease and resting left ventricular ejection fractions of less than or equal to 0.35 underwent resting metabolic cardiac imaging utilizing 1 mCi [123I]iodophenylpentadecanoic acid (IPPA) intravenously and a multicrystal gamma camera. Parametric images of regional rates of IPPA clearance and accumulation were generated. Forty-two vascular territories (22 infarcted) were evaluated by metabolic imaging as well as transmural myocardial biopsy. Despite resting akinesis or dyskinesis in 20/22 (91%) infarcted territories, 16/22 (73%) of these territories were metabolically viable. Transmural myocardial biopsies in all patients (43 sites, 42 vascular territories) during coronary bypass surgery confirmed IPPA results in 39/43 patients (91%). When compared to biopsy, scan sensitivity for viability was 33/36 (92%) with a specificity of 6/7 (86%). Eighty percent of bypassed, infarcted but IPPA viable segments demonstrated improved regional systolic wall motion postoperatively as assessed by exercise radionuclide angiography. We conclude resting IPPA imaging identifies viable myocardium, thereby providing a safe, cost effective technique for myocardial viability assessment. PMID- 1613565 TI - Noninvasive in-vivo measurement of hepatic and cardiac iron. AB - This study describes a new noninvasive in-vivo method of appraising human iron stores by nuclear resonance scattering (NRS). Manganese-56 is used as a source of 847 keV gamma rays which scatter resonantly from the iron in the liver and heart of patients with Cooley's anemia (thalassemia major). These patients have heavy iron overload that may lead to cardiac and other organ failure. The NRS iron quantitation of the liver compared favorably, in a linear fashion, with the iron in the liver biopsies. Above initial value, the hepatic iron correlates with the cardiac NRS signal. There is no correlation, however, between liver enzymes and degree of iron load. NRS appears to be a reliable method for measuring cardiac and hepatic iron. It may be repeated as needed to determine the effectiveness, selectivity and compliance to therapy and prognosis. PMID- 1613566 TI - Gastric emptying and intragastric distribution of oil in the presence of a liquid or a solid meal. AB - There is little information about gastric emptying of extracellular fat. A marker for liquid fat, 99mTc-(V)-thiocyanate, was used to compare gastric emptying and intragastric distribution of oil to that of aqueous liquid and solid meal components. Eight volunteers consumed 60 ml of 99mTc-labeled oil and 290 ml of 113m-In-labeled soup (total 505 kcal) on one day and 280 g 113mIn-minced beef (500 kcal), 60 ml 99mTc-labeled oil and 290 ml nonlabeled soup (505 kcal) on another day. In the oil/soup meal, gastric emptying of oil was slower than soup (50% emptying time 139.1 +/- 16.5 min versus 47.9 +/- 4.5 min, p less than 0.01). There was retention of oil in the proximal stomach (p less than 0.01) and retrograde movement of oil from distal into proximal stomach. In the oil/soup/beef meal, there was no difference in emptying of oil and beef from the total stomach (retention at 180 min 71.4% +/- 3.4% versus 58.3% +/- 7.6%, ns), but more oil was retained in the proximal stomach and more beef was retained in the distal stomach (p less than 0.01). The emptying rate of oil in the oil/soup meal was about twice that for oil consumed in the other meal. There was no difference between the two meals in the number of calories emptied in the first 180 min. These results demonstrate major differences in the intragastric distribution of oil compared to solid and aqueous liquid meals. PMID- 1613567 TI - Simultaneous assessment of bolus transport and contraction parameters in multiple swallow investigations. AB - A better understanding of scintigraphic findings may lead to a wider acceptance of esophageal transit studies. The purpose of this study, therefore, was to correlate standard manometric parameters with the quantitative and qualitative characteristics of liquid and semi-solid bolus transport. Twenty-nine patients were simultaneously investigated with esophageal scintigraphy and manometry. Single-swallow and sum-image data of six consecutive swallows were analyzed. No significant relationship between transit time and the velocity of the peristaltic wave could be identified, which suggests that factors other than peristaltic velocity (e.g., pharyngeal pump) essentially modulate esophageal transit. There was also no linear correlation between esophageal emptying and peristaltic amplitudes. Emptying was normal in patients with amplitudes greater than 30 mmHg and reduced in those with amplitudes less than 30 mmHg. This suggests that a threshold pressure greater than 30 mmHg is necessary to propel a test bolus adequately. Patterns in condensed images have been shown to specifically reflect the events in corresponding manometric recordings. Normal and different pathologic types of peristalsis presented analogous findings in both modalities. Thus, an analysis of the relationship between bolus transport and contraction parameters in simultaneous studies increases understanding of quantitative and qualitative scintigraphic results. PMID- 1613568 TI - Petition would ease strictures on outpatient nuclear medicine therapy. PMID- 1613569 TI - Esophageal disorders and scintigraphy: one clinician's perspective. PMID- 1613570 TI - Clinical comparison of technetium-99m-teboroxime and thallium-201 utilizing a continuous SPECT imaging protocol. AB - To examine the advantages of a 99mTc-labeled cardiac perfusion agent, teboroxime or SQ30,217 (Squibb Diagnostics), a prospective study was undertaken comparing it to 201Tl stress testing in 17 patients suspected or known of having coronary artery disease (CAD). All patients were studied utilizing a single-detector SPECT camera with a continuous acquisition imaging protocol. Testing was performed on a treadmill to comparable levels with both agents within a 2-wk period. Concordance between the two studies on a patient by patient basis was seen in 16/17 (94%) patients, and discordance was seen in 1/17 (6%) patients. Comparison of findings between 201Tl and 99mTc-teboroxime on a segment by segment basis showed concordance in 107/119 (90%) segments, and 12/119 (10%) were discordant. Both examinations independently detected an equal number of normal (77) and abnormal (42) segments. There was no significant difference between the two agents in classifying lesions as ischemic, although there were significant differences between thallium and teboroxime in classifying infarct and infarct/ischemia. Technetium-99m-teboroxime SPECT imaging is a clinically useful method for detecting CAD, with a major advantage being the shorter examination time per individual patient study. The mean total examination time for completion of the 99mTc-teboroxime study was 2.5 hr versus 4.0 hr for 201Tl. PMID- 1613572 TI - Dose estimation in strontium-89 radiotherapy of metastatic prostatic carcinoma. AB - Strontium-89 radiotherapy is becoming an important treatment in the palliation of bone pain from osteoblastic metastases. The absorbed dose delivered to bone metastases during 89Sr radiotherapy has been estimated in four patients with metastatic prostatic carcinoma. Patients were injected with a tracer dose of 85Sr chloride. Blood and urine samples were obtained during the week following injection. Strontium-85 scintigrams of metastases and normal bone were obtained up to 8 wk postinjection. Half of the patients showed elevated whole-body retention; plasma-strontium concentrations were decreased from normal values. Uptake of strontium in metastases was 2-25 times that in normal bone but rates of washout of strontium from metastases were similar to those from normal bone. Absorbed doses delivered in infinite time to the metastases by 89Sr ranged from 21 +/- 4 to 231 +/- 56 cGy/MBq with a median value of 68 cGy/MBq. Doses to red marrow were less by a factor of 2 to 50. These absorbed doses are sufficiently large to be expected to produce a therapeutic benefit. PMID- 1613571 TI - A comparison of brain perfusion SPECT in cocaine abuse and AIDS dementia complex. AB - Intravenous drug use is a major risk factor for HIV-1 infection. Since both AIDS dementia complex (ADC) and cocaine have been associated with abnormal brain perfusion imaging, we compared the scintigraphic patterns of ADC patients and cocaine polydrug users with normal control subjects using 99mTc-HMPAO SPECT. We found a high incidence of cortical defects in both ADC (100%) and cocaine dependent (90%) subjects. In the cocaine and ADC patients, cortical defects were most frequent in the frontal, temporal and parietal lobes and occurred with similar frequency in the two populations. In both groups, the number of cortical defects per subject was higher than normal subjects (10.0 +/- 5.0 for ADC, 10.1 +/- 5.2 for cocaine and 0.7 +/- 1.5 for normal), background activity was high (a 65% and 60% incidence for ADC and cocaine, respectively), and basal ganglia involvement was frequent (40% and 65% for ADC and cocaine). We conclude that the brain perfusion pattern, while a sensitive indicator of ADC, cannot be distinguished from chronic cocaine polydrug use and caution should therefore be applied before entertaining a specific diagnosis. PMID- 1613573 TI - Factors influencing serial measurements of cardiac volumes by count-based methods: effects of elevated catecholamines, position, and exercise on technetium 99m-blood radioactivity concentration. AB - Most radionuclide methods for measuring cardiac volume require a determination of the blood radioactivity concentration. Thus, changes in blood radioactivity over time or during interventions might lead to spurious volume estimates unless blood radioactivity is serially measured. The effects of elevated epinephrine, posture and exercise on 99mTc-labeled blood radioactivity concentration were studied in 15 young (mean age = 28 yr) and 14 older (mean age = 68 yr) healthy males. An epinephrine infusion of 50 ng/kg/min resulted in a 4.1% +/- 1.0% increase in 99mTc-blood radioactivity (p less than or equal to 0.001) compared to baseline. Sitting increased blood radioactivity concentration by 12.3% +/- 3.0% (p less than 0.0002) compared to the supine position and peak supine bicycle exercise caused an 11.0% +/- 1.7% increase (p less than or equal to 0.0001) compared to supine rest. There was a significantly greater increase during peak supine exercise in the young compared to the older subjects (15.0% +/- 2.3% versus 6.3% +/- 2.0%, p less than or equal to 0.01). The mechanism of the increase in blood radioactivity concentration is uncertain, but presumably reflects the addition of hemoconcentrated red blood cells from the spleen and/or the loss of plasma volume. Failure to correct for the increased blood radioactivity concentration during exercise or pharmacological interventions will result in a significant error in serial measurements of cardiac volumes by methods requiring RBC radioactivity measurements. PMID- 1613574 TI - Evaluation of infectious diabetic foot complications with indium-111-labeled human nonspecific immunoglobulin G. AB - Osteomyelitis of the foot is a well-known complication of diabetes mellitus. In this study, the validity of 111In-labeled human nonspecific immunoglobulin G (IgG) scintigraphy was studied in 16 diabetic patients with foot ulcers, gangrene or painful Charcot joints. In all patients, plain radiographs, conventional bone scan images and 111In-IgG images were recorded. The results were verified by histologic examination of surgical specimens in patients who did not respond to antibiotic treatment within 2-3 wk (10 lesions) or long-term clinical follow-up of at least 6-mo (16 lesions). On the bone scans, all seven osteomyelitic foci were detected. However, 19 additional foci not due to osteomyelitis were seen. The absence of true-negative bone scans in this study resulted in a specificity of 0%. On the plain radiographs, four of seven osteomyelitis foci were detected; for 111In-IgG scintigraphy, six of seven (sensitivity 57% and 86%, respectively). Plain radiographs correctly ruled out osteomyelitis in 15 of 19 lesions, 111In IgG scintigraphy in 16 of 19 (specificity 79% and 84%, respectively). All imaging procedures gave false-positive results in penetrating ulcers over the calcaneus in two patients and in one patient with a Charcot joint, most likely due to recent fractures. A false-negative 111In-IgG study was observed in a patient with severe arterial angiopathy. Accurate estimation of probable osteomyelitis was not possible from the results of soft-tissue cultures, since in only 6 of 12 positive cultures, osteomyelitic foci could be proven. Indium-111-IgG scintigraphy can contribute to adequate evaluation of osteomyelitis in diabetic foot complications because it improves specificity when compared to bone scan and radiographic findings and improves sensitivity in comparison to plain radiographs. PMID- 1613575 TI - Diagnostic imaging of the liver. PMID- 1613576 TI - The relationship between myocardial blood flow and glucose uptake in ischemic canine myocardium determined with fluorine-18-deoxyglucose. AB - The relationship between myocardial blood flow as a marker of severity of ischemia and exogenous glucose utilization was examined following occlusion of the left anterior descending coronary artery in 10 fasted, anesthetized, open chest dogs. Fluorine-18-fluorodeoxyglucose (FDG) was injected 10 min after the onset of ischemia and serial blood samples were obtained to measure FDG in plasma. Tracer-labeled microspheres, used to measure myocardial blood flow (MBF), were injected 10 and 40 min postocclusion. After the last microsphere injection, the heart was arrested and removed rapidly. Tissue samples of the left ventricle were obtained, weighed and FDG counts were determined. Two days later, the same samples were assayed for radioactivity from the tracer-labeled microspheres and blood flow was calculated. Thus, FDG uptake and MBF measurements were made in the same tissue samples. When normalized for variations in blood flow, there were no significant differences in FDG uptake between the subendocardial and subepicardial halves of the tissue samples. FDG uptake was relatively high and uniform in normal myocardium, paralleling the pattern of MBF. In ischemic myocardium, however, FDG uptake and MBF did not vary in parallel. In tissue samples with MBF reduced by up to 80% from control levels, relative FDG uptake increased such that absolute FDG uptake remained at normal or near normal levels. In samples with more severe ischemia, FDG uptake decreased precipitously with additional decrements in MBF. We propose that sufficient glycolytic flux may be sustained to maintain cellular viability when perfusion is above the threshold value. Below the threshold, however, irreversible changes may be initiated. PMID- 1613577 TI - Myocardial blood flow, deoxyglucose uptake, and myocyte viability in ischemia. PMID- 1613578 TI - Interspecies variation in biodistribution of technetium (2-carbomethoxy-2 isocyanopropane)6+. AB - The cationic complex technetium (2-carbomethoxy-2-isocyanopropane)6+ (99mTc-CPI) contains terminal ester groups that were included to provide a pathway for in vivo metabolism of this compound, thereby enhancing its performance as a myocardial perfusion agent. Biodistribution studies of the compound demonstrated myocardial accumulation in rabbit, guinea pig, and chick, but not in rat and mouse. Radiochemical analysis by HPLC after in-vitro incubation of 99mTc-CPI in blood plasma from the various species confirmed enzymatic hydrolysis to numerous new compounds. Rat and mouse serum produced complete hydrolysis of this agent after incubation for less than 5 sec at 25 degrees C or rates greater than 500 times those observed in human, rabbit, guinea pig and chick serum. Chemical synthesis and isolation of the monohydrolyzed species with subsequent biodistribution studies in guinea pig and rabbit confirmed that this neutral lipophilic complex did not accumulate in heart tissue. It is concluded that varying rates of enzymatic in-vivo hydrolysis produce the interspecies biodistribution differences and may account for the moderate myocardial clearance relative to other isonitrile complexes. PMID- 1613579 TI - Establishment and characterization of monoclonal antibodies against an octahedral gallium chelate suitable for immunoscintigraphy with PET. AB - As a prerequisite for preparing bispecific antibody conjugates containing anti tumor and anti-metal chelate binding sites that can be used for pretargeted immunoscintigraphy, monoclonal antibodies (Mabs) have been raised against an octahedral metal chelate synthetized from gallium (Ga) and the hexadentate ligand N,N'bis[2-hydroxy 5-(ethylene beta carboxy) benzyl] ethylenediamine N,N' diacetic acid (Ga-HBED-CC). With use of the Farr assay, binding studies with the 67Ga labeled chelate and three clones of anti-chelate Mabs showed that none of the Mabs were able to precipitate more than 50% of the Ga-chelate, suggesting an enatiomerism of the Ga-chelate and a sensitivity of the Mabs to either one or the other chelate enantiomer. This could be confirmed by comparing the circular dichroism spectra of the Ga-chelate fractions that passed affinity columns containing the Mabs immobilized on sepharose without retention. With use of a Ga HBED-CC enantiomer, whole-body retention in mice, preinjected with the corresponding anti-metal chelate Mab of ca. 70% ID, was measured compared to 2.1% retention in mice not preinjected with the Mab. Due to the high affinity of chelate-to-Mab binding in vivo, bispecific antibody conjugates prepared from the fragments of the anti-Ga-chelate Mab might be suitable for pretargeted immunoscintigraphy with the short-lived positron-emitter 68Ga. PMID- 1613580 TI - In-vivo identification of tumor multidrug resistance with 3H-colchicine [corrected]. AB - Multidrug resistance (MDR) is a major obstacle in the clinical treatment of cancer with natural-product anticancer agents. Identification of MDR in vivo could be important in the design of chemotherapeutic regimens. As a first step in developing radiolabeled drugs to detect MDR, we measured the in vivo distribution of radiolabel from [ring C, methoxy-3H]-colchicine ([3H]-CHC) in immunosuppressed mice bearing xenografts of colchicine-resistant and sensitive tumor cell lines. Experiments were done at trace (1 microgram/kg) and LD50 (4 mg/kg) dose levels. Activity concentration/injected dose was more than twice as great in sensitive as in resistant tumors (p less than 0.01) at 60 min following retroorbital injection of [3H]-CHC. There was no significant difference in activity distribution between trace- and high-dose injections for any of the tissues sampled. Chromatographic analysis of plasma and tumor extracts demonstrated extensive extravascular metabolic degradation of [3H]-CHC. The ratio of [3H]-CHC concentration of injected dose between sensitive and resistant tumors was 3:1 (p less than 0.05), due primarily to protein-bound [3H]-CHC. This preliminary study demonstrates that it is possible to distinguish multidrug resistant from sensitive tumors in vivo on the basis of radiolabel uptake from an injected MDR drug. Colchicine, labeled with 11C at the [ring C]-methoxy group, may be useful as a radiopharmaceutical for quantitative identification of MDR in human tumors using PET. PMID- 1613581 TI - Effect of carbohydrate modification on the localization of human polyclonal IgG at focal sites of bacterial infection. AB - Radiolabeled human polyclonal IgG localizes at focal sites of infection/inflammation. Previous studies have sought to identify the mechanism of localization, but the relative importance of specific antigen recognition by individual antibody molecules, binding to Fc receptors on inflammatory cells and nonspecific processes such as increased tissue permeability remains uncertain. This study was performed to evaluate the specific role of Fc receptor binding as a mechanism of localization. The Fc region of IgG was modified by endoglycosidase F digestion and periodate oxidation to reduce the binding of IgG to Fc receptors. In-vitro binding was tested in an Fc receptor binding assay using the human monocyte-like cell line, U937. The in-vivo ability of the modified antibodies to localize at focal sites of E. coli infection was tested by biodistribution studied with the 111In-labeled proteins. Modification of the carbohydrate moiety of the Fc region of IgG resulted in a marked decrease in Fc receptor binding in vitro; with antibody concentrations of 1 micrograms/ml (which is presumed to exist at infected sites) showing no binding for endoglycosidase modified IgG and 50% binding for periodate modified IgG. In contrast, in-vivo infection localization as measured by level of accumulation or target-to-background ratio was not significantly effected by carbohydrate modification. These studies suggest that the contribution of Fc receptor binding to IgG localization at sites of infection is minimal. PMID- 1613582 TI - Delayed L-phenylalanine infusion allows for simultaneous kinetic analysis and improved evaluation of specific-to-nonspecific fluorine-18-dopa uptake in brain. AB - The accumulation of 3-O-methyl-6-[18F]fluoro-L-DOPA (18F-30M-DOPA) in the brain from the circulation is responsible for most of the nonspecific background during 18F-DOPA positron emission tomography scanning. To increase the sensitivity of 18F-DOPA for imaging presynaptic dopamine systems, we took advantage of 18F-30M DOPA's rapid clearance from the brain (T1/2 approximately 15-20 min). The infusion of the unlabeled amino acid L-phenylalanine, starting 75 min after 18F DOPA administration, prevents 18F-30M-DOPA entrance into the brain through competition at the large amino acid transport system of the blood brain barrier. This method produces high specific-to-nonspecific contrast images of 18F accumulation beginning 15-30 min after onset of amino acid infusion and better sensitivity to small changes in 18F-DOPA uptake while still allowing for kinetic analysis of the data in the early time points. Kinetic and anatomical data were found to be strongly correlated. PMID- 1613583 TI - Technetium-99m-medronate uptake in hepatic necrosis associated with Budd-Chiari syndrome. AB - A 99mTc-MDP bone scan performed on a 52-yr-old female for possible bone metastasis revealed prominent hepatic uptake. Subsequently, a 99mTc-SC scan revealed tracer uptake in the caudate lobe with diminished uptake in the remainder of the liver. Further imaging with Doppler ultrasound and hepatic venography confirmed a diagnosis of Budd-Chiari syndrome. Hepatic necrosis, demonstrated on CT imaging, was secondary to Budd-Chiari syndrome and was felt to be the cause of 99mTc-MDP hepatic uptake in this patient. PMID- 1613584 TI - Comparison of technetium-99m-MIBI and thallium-201-chloride uptake in primary thyroid lymphoma. AB - A case of primary thyroid lymphoma demonstrating uptake of 99mTc-hexakis-2 methoxy isobutyl isonitrile (MIBI) is presented. The 99mTc-MIBI image more clearly delineated the extent of tumor as demonstrated on CT compared to 201Tl chloride and [99mTc]pertechnetate images. Following two courses of chemotherapy, repeat radionuclide studies and CT scan showed complete resolution of the thyroid tumor. Technetium-99m-MIBI may be useful in the assessment of disease activity and monitoring response to treatment in patients with lymphoma. PMID- 1613585 TI - Radiation safety considerations for post-iodine-131 thyroid cancer therapy. AB - The purpose of this study was to develop guidelines based on direct patient measurements as to when 131I-treated thyroid cancer patients may resume close personal contact after release from the hospital. External exposure rates were measured on 27 patients using a calibrated ionization survey meter. The patients' exposure rates were measured at the time of release from the hospital and 2-7 days post-hospital discharge. Measurements were taken at 1, 0.6 and 0.3 meters from the patient's upright body axis (stomach to thyroid). Vertical movement of the survey instrument was utilized to obtain the maximum reading each time. All patients had exposure rates less than 2 mR/hr at 1 meter at 2-4 days post hospital discharge. Eight-eight percent (21/24) had exposure rates less than 2 mR/hr at 0.6 meter at 2-4 days post-hospital discharge. Guidelines can be prepared specifically for thyroid cancer therapy patients that are rational and consistent with existing radiologic health standards. PMID- 1613586 TI - Optimization of follow-up measurements of bone mass. AB - In bone densitometry, the precision of the instrument, the number of measurements and the time-points of the measurements are important criteria for monitoring bone mass changes. The most appropriate follow-up procedure can be determined by numerical comparison of various combinations of these three criteria. This can be done by computing the confidence interval of changes in bone mass. We developed a model to estimate the length of a confidence interval for the observed changes in individual patients. With specific instrument precision, a specified number of measurements and, assuming a linear rate of bone mass changes, the best estimate of the actual changes in bone mass is obtained by measurements at the end of an observation period. With the current precision of bone densitometers, follow-up of patients with yearly duplicate measurements is recommended. A shorter scan time interval offers no additional information unless very rapid bone loss is expected. PMID- 1613587 TI - Left ventricular perfusion and performance from a single radiopharmaceutical and one camera. AB - To test the hypothesis that a small field of view portable multicrystal scintillation camera can perform stress/rest combined LV function by first-pass and perfusion studies using 99mTc-teboroxime, 26 patients with positive stress thallium studies within 2 wk and 8 healthy volunteers were studied. A 241Am point source marker over the sternum was used for motion correction. Dynamic dual isotope (99mTc/241Am) acquisition was performed following injection of 15.6 +/- 2.3 mCi of 99mTc-teboroxime at peak treadmill exercise. Two minutes later (blood pool clearance), while still standing on the flat treadmill, 3-4 40-sec planar images were acquired. One hour later patients were reinjected with 22.7 +/- 3.4 mCi of 99mTc-teboroxime while standing in front of the camera and the same dynamic/static acquisition protocol repeated. The planar images were interpolated from a 20 x 20 matrix to a 160 x 160 matrix, a sharpening filter and an interpolative background subtraction algorithm applied. The scans were divided into segments, each scored as normal, reversible and fixed. The agreement with thallium imaging for identifying an abnormal scan was 24/26 (92%) and for identifying abnormal vascular territories was 43/52, (83%). Fourteen patients had exercise LVEF less than 50% and all had either prior myocardial infarction, myocardial infarction plus ischemia or LAD ischemia. Diagnostic planar perfusion images and exercise LVEF can be acquired in less than 4 min using 99mTc teboroxime and a portable multicrystal scintillation camera. PMID- 1613589 TI - Lung scan interpretation: a physiologic, user-friendly approach. PMID- 1613588 TI - Lung scan interpretation: a physiologic, user-friendly approach. AB - A physiologically-oriented, user-friendly algorithm for interpretation of ventilation-perfusion (V/P) lung scans was compared to the widely used Biello criteria. The physiologic algorithm relies primarily on the observer's degree of certainty that a V/P mismatch is present rather than on the size (relative to a whole segment) and number of V/P mismatches. One hundred five patients who had undergone a ventilation study with 133Xe gas, a perfusion study with 99mTc-MAA and pulmonary angiography were reviewed. Each V/P lung scan was interpreted once with the physiologic algorithm and once with the Biello criteria by two observers. Fifty-nine percent of the 105 studies were classified as indeterminate with the physiologic algorithm versus 62% with the Biello criteria. The prevalence of pulmonary embolism in the high probability, indeterminate, low probability and normal categories for the physiologic algorithm were 60%, 26%, 7% and 0%, respectively; and for the Biello criteria were 50%, 31%, 11% and 0%, respectively. Analysis of the data with receiver-operating-characteristic curves indicated that the physiologic algorithm performed better than the Biello criteria (p less than 0.05). In addition, the physiologic algorithm has the advantages of being more intuitive and easier to remember. We conclude that further evaluation of the physiologic approach for the interpretation of V/P lung scans is warranted. PMID- 1613590 TI - Blunted response of myocardial perfusion to dipyridamole in older adults. PMID- 1613591 TI - Marrow scintigraphic changes after hormonal therapy. PMID- 1613592 TI - The localization of indium-111-leukocytes, gallium-67-polyclonal IgG and other radioactive agents in acute focal inflammatory lesions. PMID- 1613593 TI - Standardized tests of PET performance. PMID- 1613594 TI - Patterns of dementia in Alzheimer's disease. PMID- 1613595 TI - Berson-Yalow Award winners shedding light on FDG uptake in tumors. PMID- 1613596 TI - Radiopharmaceutical chemist receives Hevesy Nuclear Medicine Pioneer Award. PMID- 1613597 TI - Certification for nursing staff development educators. PMID- 1613598 TI - A creative recruitment program. Future nurses' camp. AB - Attracting high school students into nursing is a concern of staff development educators. "Future Nurses' Camp" was a creative, cost-effective program developed by a hospital education department. A 2-week, fun-filled, informative camp that included the use of high-tech equipment and patient-care decision games promoted a positive image of nursing. Experiencing nurses' roles reinforced the students' desire to enter nursing. PMID- 1613599 TI - Education centers. What features are best? AB - Nurse educators in the 1990s need to conserve resources, decrease duplication in staff training efforts, maintain educational quality, and provide a flexible learning environment. Educators at the University of Minnesota Hospital and Clinic in Minneapolis find these goals easier to achieve since they designed an education center in 1986. Orientation, continuing education, inservice, and skills fairs are some activities that take place in the center. In this article, the authors describe the center and give useful tips for readers interested in developing a similar facility. PMID- 1613600 TI - A nursing update course. Service and education collaborate. AB - This article describes the planning, development, implementation and evaluation of a nursing update course. It identifies collaboration between a hospital and college as the key element in the program's success. Evaluation showed the program was effective in recruiting and educating students; it helped alleviate a local nursing shortage and brought nursing practice and education together, and 87% of the course participants either returned to practice or entered formal education programs to continue their professional development. PMID- 1613601 TI - Education day. The evolution of a learning experience. AB - Education Day in our hospital was created as a way of increasing attendance at annual mandatory inservices. Since beginning the program, compliance with mandatory inservice has increased from 50% to 97%. The Education Day format consolidates resources and provides consistency in the delivery of required information. The format is also flexible; it responds to changes and specialized educational needs of the nursing staff. PMID- 1613602 TI - Self-learning packages in staff development. AB - Potential uses for self-learning packages in the nursing staff development setting include orientation programs, mandatory education programs, developmental programs, and review of infrequently used skills. The staff development educator can use pretest and posttest results obtained from the use of self-learning packages to document intervention with the learner. Benefits for both learners and staff development educators when this teaching strategy is used are described. PMID- 1613603 TI - A guide to competency-based orientation. Develop your own program. AB - Nursing orientation should provide the requisite knowledge and skills to enable a nurse to perform competently in a new work environment. This article provides a step-by-step guide to the development of a competency-based orientation program that is supported by well-developed preceptors. It is written in a "how-to" format, providing the guidance and tools necessary for a nurse educator to develop a program that is institution specific. PMID- 1613604 TI - Implementing self-learning. PMID- 1613605 TI - A theory-based computer training program. AB - Using Kolb's learning theory resulted in an effective method of implementing a computer training program. The variety of teaching strategies provided an environment for nurses and other health care providers with different learning styles to understand and use the computer system successfully. The comprehensive training program was critical to the successful conversion to a new computer system in this large public teaching hospital. This project reinforces the need for nursing education and research departments to use teaching strategies that accommodate a variety of learning styles in a heterogenous group. The results of this project suggest one approach to stimulate adult learning and facilitate an effective learning environment. Nurses and other computer users have demonstrated effectiveness of this training program through successful activation of the new computer system. PMID- 1613606 TI - Assessing learning outcomes. PMID- 1613607 TI - Patterns of syphilis testing in the elderly. AB - OBJECTIVE: To evaluate the frequency of inconsistencies in the use of laboratory tests for syphilis among the elderly in an acute care setting. DESIGN: Retrospective medical record review. SETTING: Academic medical center. PATIENTS/PARTICIPANTS: All patients 60 years of age and older who had: 1) positive tests for syphilis and no lumbar puncture performed (n = 71), 2) lumbar punctures performed and no positive test for syphilis (n = 68), and 3) positive tests for syphilis and lumbar punctures performed (n = 8). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The chronology and results of syphilis tests were abstracted from the medical records. Documentation of signs and symptoms of neurosyphilis, including dementia and depression, were abstracted from the medical records by a second reviewer. Most patients had inadequate evaluations; 51 had no follow-up of positive syphilis tests and 43 had cerebrospinal fluid syphilis tests in the absence of positive blood tests for syphilis or signs and symptoms of neurosyphilis. CONCLUSIONS: The inconsistent pattern of serologic testing in this study suggests that the testing was done as a routine procedure and not for a specific purpose. For a majority of the tested individuals, the results did not provide a public health benefit or contribute to the individual's well-being. PMID- 1613608 TI - Fatigue in primary care: prevalence, psychiatric comorbidity, illness behavior, and outcome. AB - OBJECTIVES: To identify the prevalence, psychiatric comorbidity, illness behavior, and outcome of patients with a presenting complaint of fatigue in a primary care setting. METHODS: 686 patients attending two family medicine clinics on a self-initiated visit completed structured interviews for presenting complaints, self-report measures of symptoms and hypochondriasis, and the Diagnostic Interview Schedule (DIS). Fatigue was identified as a primary or secondary complaint from patient reports and questionnaires completed by physicians. RESULTS: Of the 686 patients, 93 (13.6%) presented with a complaint of fatigue. Fatigue was the major reason for consultation of 46 patients (6.7%). Patients with fatigue were more likely to be working full or part time and to be French Canadian, but did not differ from the other clinic patients on any other sociodemographic characteristic or in health care utilization. Patients with fatigue received a lifetime diagnosis of depression or anxiety disorder more frequently than did other clinic patients (45.2% vs. 28.2%). Current psychiatric diagnoses, as indicted by the DIS, were limited to major depression, diagnosed for 16 (17.2%) fatigue patients. Patients with fatigue reported more medically unexplained physical symptoms, greater perceived stress, more pathologic symptom attributions, and greater worries about having emotional problems than did other patients. However, only those fatigue patients with coexisting depressive symptoms differed significantly from nonfatigue patients. Patients with fatigue lasting six months or longer compared with patients with more recent fatigue had lower family incomes and greater hypochondriacal worry. Duration of fatigue was not related to rate of current or lifetime psychiatric disorder. One half to two thirds of fatigue patients were still fatigued one year later. CONCLUSIONS: In a primary care setting, only those fatigue patients who have coexisting psychological distress exhibit patterns of abnormal illness cognition and behavior. Regardless of the physical illnesses associated with fatigue, psychiatric disorders and somatic amplification may contribute to complaints of fatigue in less than 50% of cases presented to primary care. PMID- 1613610 TI - The medical problems of homeless clinic patients: a comparative study. AB - OBJECTIVE: To compare the prevalence of major medical problems in homeless and nonhomeless patients. PATIENTS: All 475 persons seeking care at an ambulatory clinic serving the medically indigent for one calendar year. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical data were collected by structured interviews and medical record reviews for all patients seeking care at the clinic between March 1989 and April 1990. Comparisons were made between homeless patients, those patients with unstable housing, and those with stable housing. There was no significant between-group difference in age, gender, ethnicity, and health insurance coverage. Homeless patients were more likely to be unemployed (p less than 0.001) and were found to have higher prevalence of alcohol abuse, injuries/fractures, and dental and gynecologic problems (p less than 0.05). CONCLUSIONS: There were more similarities than differences in the prevalences of major medical problems in homeless vs. nonhomeless community clinic patients. Where differences did exist, homeless persons consistently had a higher prevalence of illness than did the nonhomeless. PMID- 1613609 TI - Natural history of symptoms of depression and anxiety during inpatient treatment on general medicine wards. AB - OBJECTIVE: To establish the frequency of criteria-based depression and anxiety in newly admitted medical inpatients and to determine the natural history of depressive and anxiety symptoms during hospitalization. DESIGN: Prospective structured assessment of criteria-based depression and anxiety diagnoses within 24 hours of hospitalization with routine follow-up depression and anxiety questionnaires until discharge. SETTING: A tertiary care university hospital and an affiliated Veterans Administration hospital. PATIENTS: One hundred twenty eight adult patients admitted to internal medicine inpatient units between May 1990 and August 1990. MAIN RESULTS: On admission, 43 of the 128 patients inducted met the DSM-III criteria for major depression, while an additional six met the criteria for adjustment disorder with depressed mood. Only six patients met the criteria for panic disorder, generalized anxiety disorder, or adjustment disorder with anxious mood at the time of admission to the study. Patients with high symptom scores on the anxiety and depression scales showed significant decreases in these scores without specific psychiatric intervention. Those who remained in the hospital 20 days or longer showed initial improvement and subsequently returned to baseline symptom levels of depression and anxiety. In approximately 9% of patients, symptoms of depression persisted or worsened. CONCLUSIONS: Major depression occurs more commonly than anxiety disorder in newly admitted medical inpatients but both resolve spontaneously in the majority during the course of hospitalization without specific psychiatric intervention unless the hospitalization is prolonged. One in ten will continue to show symptoms of depression. PMID- 1613611 TI - A physician-completed patient registry system: pilot results for unstable angina in the elderly. The Northern New England Cardiovascular Disease Study Group and the Dartmouth Primary Care COOP. AB - OBJECTIVE: For many common conditions, such as unstable angina pectoris (UAP) in the elderly, the course of the disease and the influence of treatments on outcome need to be better described. In this report the authors demonstrate how a simple pocket-sized card system can be used by busy clinicians to identify patient cohorts and follow the courses of their illnesses. DESIGN AND SETTING: Twelve university-based and 12 rural clinicians enrolled consecutive patients over the age of 64 with UAP. One week and six weeks after patient enrollment the physicians described treatments, diagnoses, and patient outcomes. RESULTS: The median age of the 76 patients was 73 years. Within one week of enrollment for UAP, ten (13%) suffered myocardial infarctions or died; by six weeks this adverse event rate was 26%. The presence of three or more clinical criteria for UAP (odds ratio 9.9; 95% CI 2.4-41.5) and "ST changes" by electrocardiography (odds ratio 9.5; 95% CI 2.5-35.6) were strongly associated with death or myocardial infarction within a week after enrollment. CONCLUSION: These findings suggest that the use of a clinician-completed patient registry will allow designation of clinically important high- and low-risk UAP. A registry system such as that described here may be useful for the initial evaluation of treatment and outcomes of illness. PMID- 1613613 TI - Variation in physician opinion about scheduling of return visits for common ambulatory care conditions. AB - OBJECTIVE: To determine whether there is consensus about intervals between visits for adult general medicine patients with common ambulatory care conditions. DESIGN: Survey of practicing physicians and residents. SETTING: Ambulatory care at a hospital clinic, a group practice, and a physician office. PARTICIPANTS: 153 physicians, including residents, fellows, and staff from The University of Iowa Hospitals and Clinics, internists and family practitioners from three Iowa towns, and internists from Atlantic City, New Jersey. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There was wide variation in responses, with greater consensus for more acute conditions than for chronic conditions or preventive care. CONCLUSIONS: 1) Wide variation exists in proposed intervals between visits for care of patients with common ambulatory conditions. 2) Variation occurs within the same geographic area and is unassociated with year of graduation from medical school, year in training, or academic appointment 3) Further study is needed to assess the significance of this variation. PMID- 1613612 TI - Diagnostic judgments of nurse practitioners providing primary gynecologic care: a quantitative analysis. AB - OBJECTIVES: To determine the accuracy of experienced nurse practitioners' judgments of the probability of chlamydial infection of the cervix, to identify the clinical factors ("cues") related to the judgments, and to discern likely sources of judgment error. DESIGN: Cross-sectional study with prospective data collection. SETTING: Urban hospital-based clinic. PATIENTS: 492 nonpregnant women receiving primary gynecologic care. INTERVENTIONS: Four nurse practitioners recorded clinical data, tested women for chlamydial infection, and judged the probability of chlamydial infection using six categories: less than 1%, 1-4%, 5 9%, 10-24%, 25-50%, and greater than 50%. MEASUREMENTS AND MAIN RESULTS: Chlamydial infection was detected by immunofluorescent assay in 31 (6%) of the 492 women. Although the median probability judgment was 5-9%, judgments were only weakly related (p = 0.08) to actual rates of infection. In a multivariate analysis, eight clinical cues were independently (p less than 0.05) related to nurse practitioners' probability judgments: age less than 20 years; past chlamydial or gonococcal infection; new sex partner; partner with suspected genital infection; genito-urinary symptoms; cervicitis, purulent vaginal discharge; and malodorous vaginal discharge. A linear model based on the eight cues, weighted according to their regression coefficients, predicted chlamydial infection more accurately than did the nurse practitioners' actual judgments (ROC curve areas 0.69 vs. 0.58, respectively; p less than 0.05). However, only two of the eight cues (age less than 20 years and purulent vaginal discharge) were actually related to chlamydial infection in a second multivariate model; this model bad accuracy similar to that of an empirically derived prediction rule (ROC curve areas 0.77 and 0.80, p = 0.27). CONCLUSIONS: Nurse practitioners were often inaccurate in their diagnostic judgments. Our analyses suggest that this inaccuracy stemmed from both the inconsistent use of clinical cues and the use of cues that were not related to chlamydial infection. Therefore, interventions such as algorithms that promote consistency and accuracy in diagnostic use of relevant cues would be likely to improve their diagnostic judgments. PMID- 1613614 TI - Cardiovascular risk modification in the college student: knowledge, attitudes, and behaviors. AB - STUDY OBJECTIVES: To study knowledge, attitudes, and behaviors regarding cardiovascular risk in college students, and to delineate preferred modes of gaining further information. DESIGN: Cross-sectional survey. SETTING: Four-year public liberal arts college. PARTICIPANTS: 1,503 students returning a questionnaire (response rate of 60.4%). RESULTS: Over 91% of respondents knew hypertension was a major cardiovascular risk factor. In addition, 90% identified smoking, 86.7% identified cholesterol level, and 72% identified exercise as additional factors. Under 16% reported that they smoked cigarettes, but only 33.5% exercised regularly. Only 32.9% had had cholesterol levels checked, with 19.2% knowing their values. Over 94% named doctors and nurses as desired sources of further information, yet only 23% said doctors had previously discussed prevention of heart disease with them. CONCLUSIONS: General knowledge of cardiac risk factors is high among college students, yet actual behavior does not necessarily reflect assimilation of these concepts. Students seek health information from traditional sources. Primary care physicians have a unique opportunity to address these issues, especially in the pre-college physical examination. PMID- 1613615 TI - Quality of emergency room triage of medical inpatients to an acute care clinic or chronic health care facilities. AB - OBJECTIVE: To evaluate the accuracy of emergency room triage by general internists assigning medical patients to four different health care settings. DESIGN: Prospective trial. SETTING: Medical emergency room of a university hospital providing primary and referral care. PATIENTS: 974 consecutive patients admitted for acute medical care, excluding patients admitted to intensive care units. INTERVENTION AND MEASUREMENTS: After primary evaluation patients were assigned to one of four groups: A) acutely ill requiring acute care in a general medical ward (n = 598); B) acutely ill requiring acute care limited to two to three days (n = 201); C) chronically ill with realistic chances for rehabilitation (n = 77); and D) chronically ill requiring definite referral to skilled nursing home care (n = 98). Nine months later, outcome and placement after index hospitalization were evaluated in surviving patients. MAIN RESULTS: 159 (16%) patients died; three (1%) were lost to follow-up. Evolution confirmed the appropriateness of the initial triage of 90% of the remaining 812 patients (83%). Allocations were correct in 96%, 95%, and 91% of cases in groups A, B, and C, respectively. In group D, only 44% were definitely transferred to nursing homes; 56% were rehabilitated and returned to their previous social settings or entered homes for the aged. CONCLUSIONS: Clinical judgment of general internists in an emergency room adequately identifies patients requiring acute care of regular or short duration and chronically ill patients with realistic prospects for rehabilitation. But the need for nursing home placement is overestimated. To avoid patient misplacement the authors propose direct access to a specialized geriatric assessment facility. PMID- 1613616 TI - Painful shoulder syndromes: diagnosis and management. AB - Painful shoulder conditions are common primary care problems. Providers should learn the topographical landmarks about the shoulder and understand shoulder mechanics. A careful clinical evaluation will usually provide a likely diagnosis. In unclear cases with marked pain, weakness, and reduced mobility, or with a suspected rotator cuff tear or rupture, arthrography or MRI will usually establish a diagnosis. Therapy of bursitis/tendinitis consists of a steroid injection into the inflamed subacromial area or a 14-day trial of an NSAID. Therapy of bicipital tendinitis, largely empiric because definitive studies are unavailable for any specific treatment, includes judicious peritendinous steroid injections and avoiding aggravating activities. In the management of patients with suspected tendon tears or rupture, primary care practitioners can confirm the diagnosis by ordering MRI or arthrography before referring these patients to an orthopedist for definitive surgical therapy. Optimal management of adhesive capsulitis remains unclear, but an intraarticular steroid injection appears beneficial at least in temporarily diminishing pain. Pendular motion exercising is also an integral part of therapy. Deleterious effects of peribursal or intraarticular steroid infiltration appear minimal; but injections into the tendon or frequent, repetitive injections are contraindicated. Each shoulder condition has a variable course, depending on the structure(s) and extent of involvement. PMID- 1613618 TI - Clinical activities and satisfaction of general internists, cardiologists, and ophthalmologists. AB - To define factors that affect the levels of practice satisfaction of different specialities, an observer recorded the activities of 15 physicians in practice (nine general internists, three cardiologists, and three ophthalmologists) as they examined 304 clinic patients. General internists reported less satisfaction with their clinics than did the other physicians and attributed their satisfaction primarily to successful social interaction in 54% of visits, while cardiologists most often derived satisfaction from intellectual stimulation (50%) and ophthalmologists from medical success (81%). The general internists whom the authors observed are less satisfied with clinical encounters than are cardiologists and ophthalmologists and derive satisfaction mostly from social interaction, not biomedical aspects of care. PMID- 1613619 TI - Adult-onset Still's disease with a significant rheumatoid factor: examining proper use of diagnostic and classification criteria. AB - A case is presented of a 32-year-old man with classic clinical adult-onset Still's disease, who had an initially elevated (1:320) but not persistently high rheumatoid factor. Since lack of a high rheumatoid factor is one feature in the proposed classification criteria for adult-onset Still's disease, the patient was given a diagnosis of rheumatoid arthritis. The faulty reasoning behind this diagnosis of rheumatoid arthritis is discussed, focusing on the inappropriate use of classification criteria for individual clinical diagnosis, as well as the occasional need for longitudinal diagnosis. PMID- 1613620 TI - "Optimal" cost-effectiveness analyses? PMID- 1613621 TI - When is hospitalization necessary? PMID- 1613622 TI - Characterization of the intrinsic properties of the anterior cruciate and medial collateral ligament cells: an in vitro cell culture study. AB - The poor healing abilities of the anterior cruciate ligament (ACL) in contrast to those of the medial collateral ligament (MCL) are well known. Different intrinsic properties of the constituent cells of these ligaments have been proposed to be one of the factors in the differential repair mechanisms. To examine this hypothesis, we have established primary cell lines of ACL and MCL from the tissue explants of approximately similar dimensions and have studied their behavior in vitro. The outgrowth of cells from ACL explants was slower than from MCL explants, as shown by the size of the surrounding clusters of cells. Both ACL and MCL cultures exhibited typical fibroblastic morphology. No significant differences were observed in either attachment or growth of cells from the attached explants derived from various segments of ACL and MCL. Growth curves of ACL and MCL cultures at both passage numbers 2 and 6 showed a slower rate of proliferation of ACL cells than MCL cells (p less than 0.005). DNA synthesis measured in terms of [3H]thymidine incorporation (CPM/10(3) cells) of both log phase (ACL = 607.5 +/- 5.4 vs. MCL = 1356.4 +/- 11.3) and confluent (ACL = 83.0 +/- 3.6 vs. MCL = 189.8 +/- 5.4) cultures, supports the conclusion that differential proliferation rates of these cells exist in culture. FITC-phalloidin staining (for actin) of later passage cultures (P3-P5) showed a spread-out appearance of ACL cells and an elongated appearance of MCL cells. Relatively more stress fibers were seen within ACL cells. SDS-PAGE and Western blot analysis of cellular proteins revealed higher actin (43 kDa) content in ACL cells than in MCL cells. In vitro wound closure assay was performed by creating a uniform wound of 0.6 mm width in the confluent layer of ACL and MCL cultures. By 48 h postwounding, cell-free zones created in ACL cultures were occupied partially by single cells in a nonconfluent fashion. In contrast, the wounded zone in the MCL cultures was almost completely covered by the cells. Results presented in this report demonstrate a lower proliferation and migration potential of ACL cells in comparison with MCL cells. These differences in intrinsic properties of ACL and MCL cells that were observed in vitro might contribute to the differential healing potentials of these ligaments in vivo. PMID- 1613617 TI - Medical care of the elderly in the nursing home. PMID- 1613624 TI - Healing of the medial collateral ligament following a triad injury: a biomechanical and histological study of the knee in rabbits. AB - The effect of a partial medial meniscectomy and anterior cruciate ligament (ACL) transection on medial collateral ligament (MCL) healing was studied in skeletally mature rabbits. Two groups of animals, group I (isolated MCL rupture) and group II (MCL rupture with ACL transection and partial medial meniscectomy), were examined. At 6 and 12 weeks postoperatively, histological examination of the healing MCL and biomechanical evaluation of the varus-valgus (V-V) knee rotation and tensile properties of the femur-MCL-tibia complex (FMTC) were performed. Group II animals experienced substantial joint degeneration by 6 weeks. Progressive osteophyte formation was observed adjacent to the MCL insertions along with proximal migration of the MCL tibial insertion between 6 and 12 weeks. Histologic examination of the healing MCL substance from both groups showed disorganized collagen, inflammation, and fibroblast proliferation that decreased over time. For group II knees, the V-V knee rotation was found to be significantly elevated (4.7 to 5.2 times the contralateral control), and did not decrease with time. In contrast, the V-V knee rotations of the group I specimens were 1.8 times greater than control immediately following injury, and approached control values by 12 weeks. Tensile testing of the FMTCs revealed that the ultimate load increased with time for both groups, but group I had significantly higher values than group II. The linear stiffness in group I was not different than that group II and did not increase with time. For the mechanical (material) properties of the healed MCL substance, the modulus of the healing tissue for group II was only 40% that of group I. The structural properties of the FMTC and the mechanical properties of the MCL substance from both groups at 6 and 12 weeks were significantly different from the contralateral controls. We further demonstrated that immediately after ACL reconstruction, the V-V rotation of group II knees could be restored to group I levels. Recent clinical studies of MCL healing following isolated complete ligament tears have suggested that nonoperative management without immobilization leads to excellent treatment outcome. However, in more severe injuries involving additional tissues, poor quality of the healed ligament tissue and articular degeneration are observed. Our results demonstrate the deleterious effects of an untreated triad injury on the healing of the MCL substance and its insertions. Examination of the MCL substance suggests that a much larger healing mass is formed following a triad injury, which partially compensates for inferior ligament mechanical properties.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1613623 TI - Primary and coupled motions in the intact and the ACL-deficient knee: an in vitro study in the goat model. AB - Quadrupeds are commonly used as animal models to study healing of anterior cruciate ligament (ACL) reconstructions. While rabbits, dogs, goats, and sheep have been used, goats and sheep are increasingly being employed because of the larger joint size that facilitates surgery, ease of availability, and lower expense to maintain in the farm environment. In spite of this, little is known about the function of the ACL in controlling primary and coupled motions in the quadruped. We report here on the measurements of these motions in goats, with the application of anterior-posterior forces, varus-valgus moments, and internal external moments in the intact and ACL-deficient knee. Sectioning the ACL caused significant increases in primary anterior translation, and in varus-valgus and internal rotations. The increases in anterior translation were similar in amount and dependence on flexion angle to those seen in human knees. The increase in varus averaged 7 degrees and did not depend on flexion angle, whereas the increase in valgus was significant only in the flexed knee. The increases in internal tibial rotation were greatest in extension, whereas the increases in external rotation were small and independent of flexion angle. When the ACL was cut, coupled internal rotation increased with an anterior force as well as a valgus moment. Large increases were seen in coupled anterior translation with the application of varus and valgus moments, whereas smaller increases were seen with internal and external moments. These findings demonstrate that the ACL restrains multiple motions in the goat knee. This study also provides baseline data for future studies of ACL reconstruction. PMID- 1613626 TI - Quantitation of in situ contact areas at the glenohumeral joint: a biomechanical study. AB - Glenohumeral arthritis may result from abnormal articular mechanics, and shoulder reconstructive procedures often rely implicitly on the belief that the restoration of normal articular mechanics is required to obtain satisfactory clinical results. Despite this, limited knowledge of normal or pathologic glenohumeral joint articular mechanics and contact is available. This study uses a stereophotogrammetry technique to determine contact areas in normal cadaver glenohumeral joints with intact ligaments and capsule through a large range of motion using simulated forces of the four rotator cuff muscles and three deltoid heads. All shoulders were first elevated to their maximum elevation in the scapular plane at an external rotation (starting rotation = 40 +/- 8 degrees), which allowed each shoulder to attain its maximal elevation in the scapular plane, and then repeated at 20 degrees internal to this rotation. Contact areas consistently increased with increasing elevation until 120 degrees to an average of 5.07 cm2 before decreasing with further increased elevation to an average of 2.59 cm2 at 180 degrees of total arm elevation. At 20 degrees internal to the starting rotation, contact areas reached high values 60 degrees earlier (averaged 4.56 cm2 at 60 degrees of total arm elevation) and then remained fairly constant through 120 degrees before decreasing with further increased elevation to 2.51 cm2 at 180 degrees total arm elevation. With increasing elevation in the external starting rotation, humeral head contact dramatically migrates from an inferior region to a superocentral-posterior region while glenoid contact shifts posteriorly. When the humeral shaft is positioned 20 degrees internal to the starting rotation, humeral head contact shifts from inferocentral-anterior to superocentral-posterior regions. Simultaneously, a similar posterior shift in glenoid contact is observed. Furthermore, whereas only a small portion of the humeral head surface area is in contact in any given position, contact on the glenoid surface is much more uniformly distributed over its entire articulating surface. PMID- 1613625 TI - Development of vascularization in the chondroepiphysis of the rabbit. AB - Although numerous studies have addressed the presence of cartilage canals within developing epiphyses, the chronology of their appearance and their vascular contribution to the developing chondroepiphysis remain to be studied. We have selected a model, similar to the developing human skeletal system, in which extensive cartilage canal development precedes the subsequent secondary ossification process. In the rabbit proximal tibia, both chondroepiphyseal and vascular (cartilage canals) development were quantified from the first evidence of vessels until the formation of the secondary center of ossification. The volume of hyaline cartilage increased 25 times after intraepiphyseal vessels were initially observed. The blood supply, measured in cartilage canal volume, increased 400-fold over the same period. Three distinct cartilage canal morphologies were identifiable before the formation of the secondary center of ossification: (a) an early phase, in which the canals appeared as infoldings derived from the perichondrium; (b) a reactive phase, occurring simultaneously with chondrocyte hypertrophy and characterized by a very large increase in mesenchymal cells within the cartilage canal; and (c) a vascular phase, coincident with mineralization of the matrix, in which the familiar, unitary canal morphology was replaced by that of a vascular plexus. While matrix mineralization and the formation of bone seem dependent on critical cellular events, notably chondrocyte hypertrophy, the role that the vascular supply plays in developing sufficient biological inertia for the ossifying transition must not be underestimated. PMID- 1613627 TI - Contact characteristics of the subtalar joint: load distribution between the anterior and posterior facets. AB - The pressure distribution properties of the normal talocalcaneal joint were studied in 13 fresh cadaver specimens using pressure-sensitive film. The film was inserted into the joint through a posterior approach for the posterior facet and an anteromedial approach for the anterior/middle facet. Specimens, comprising the distal half of the tibia and fibula and the intact ankle and foot, were positioned in neutral in the sagittal plane. In the coronal plane, specimens were positioned in neutral, inversion, or eversion, and the contact characteristics were determined in varying positions, with and without loading the fibula, under axial loads of 350 N, 700 N, 1,050 N, and 1,400 N. The transducers were video imaged for quantitative analysis of area and pressure. The contact/joint area ratio increased significantly with applied load in the posterior facet [e.g., in eversion from 0.336 (SD = 0.195) at 350 N to 0.631 (SD = 0.225) at 700 N], as did the proportion of the contact area greater than 6 MPa, indicating an increase in contact pressure. The contact/joint area ratio was significantly lower in inversion than in any other position of the foot; however, high-pressure zones were similar, indicating that higher pressures occur in inversion. In the anterior/middle facets both contact/joint area ratio and high pressure/contact area ratios increased significantly to 700 N, but not with further load increase. At 350 N the anterior/middle facet contact area was 31% that of the posterior facet, yet it carried 63.3% of the load of the posterior facet, so its mean contact pressure was 1.44 MPa compared with 0.93 MPa for the posterior facet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613628 TI - Contact characteristics of the subtalar joint: the effect of talar neck misalignment. AB - In this study we determined the effects of misalignment of the talar neck on the contact characteristics of the subtalar joint. Each of seven fresh cadaver lower extremities was mounted in a loading jig and a vertical load was applied, 90% of which was directed through the tibia and 10% through the fibula. The foot was allowed to displace freely in the horizontal plane so that relative rotations, known to occur in the subtalar joint, would not be prevented. Pressure-sensitive film, inserted into the posterior and anterior/middle articulations, was used to quantify changes in contact characteristics. After testing in the normal condition, the talar neck was osteotomized and stabilized with internal and external skeletal fixation. Contact characteristics were then determined in each of the following stages: anatomic realignment, or with 2-mm displacement of the talar neck either dorsally, medially, laterally, or complex (dorsal and varus) with respect to the body of the talus. Measurements showed no significant changes in overall contact area or high pressure area in the posterior facet, although four of the seven specimens demonstrated increased localization of the contact area into two discrete regions. The combined anterior/middle facet, on the other hand, was significantly unloaded by all but medial displacement of the talar neck. An extraarticular load path and/or increased loading directly on the talonavicular joint was presumed to account for the loss of load transfer in the talocalcaneal joint. PMID- 1613629 TI - Correlating magnetic resonance imaging with the biochemical content of the normal human intervertebral disc. AB - Magnetic resonance imaging was used to determine the T2 relaxation times of prepared proteoglycan solutions and of normal human intervertebral disc tissue from the annulus fibrosus (AF) and nucleus pulposus (NP). The collagen, proteoglycan, and water contents of the disc tissue samples were determined by biochemical assays after they were scanned. Correlations among 1/T2, collagen, proteoglycan, and water contents of the tissue samples and among 1/T2, water, and proteoglycan contents of the proteoglycan solutions were calculated. A moderate negative correlation between 1/T2 and water content was noted for the tissue samples, and a very high negative correlation was found between 1/T2 and water content for the proteoglycan solutions. The very high positive correlation between 1/T2 and proteoglycan content of the proteoglycan solutions is probably due to this negative correlation between 1/T2 and water content. There was no significant correlation between 1/T2 and proteoglycan content of the tissues. The moderate positive correlation between 1/T2 and collagen content is probably due to the high negative correlation between collagen content and water content. No significant correlation was found between the collagen and proteoglycan contents of the tissues. Thus it appears that the data confirm previous reports in the literature that the collagen of the disc tissue functions to control its water content. PMID- 1613630 TI - Fibrillar collagen-biphasic calcium phosphate composite as a bone graft substitute for spinal fusion. AB - The osteoconductive capacity of fibrillar collagen-biphasic calcium phosphate composition was compared to autogenous bone in a canine spinal fusion model. All animals underwent a standard intervertebral body fusion (L2-L4) with rigid internal fixation and received either autogenous bone alone or a mixture of the ceramic and autogenous bone (3:1) as the graft material. Animals were followed for 12 months and the quality of fusion in each animal assessed by biomechanical testing and histological analysis. The fused L2-L4 segment of each dog was embedded in bone cement and mounted in a specially designed mechanical tester for testing in flexion, extension, and side bending. Overall, the mean rigidity of the fusion mass was not significantly different between the two groups [10.5 +/- 4.1 (SD) for autogenous bone vs. 11.3 +/- 1.7 for the ceramic plus autogenous bone, p greater than 0.05]. Similar findings were obtained for mean bending moment, compressive load, angular deformation, and energy absorbed for the two groups. Histological analysis was performed on transverse nondecalcified specimens. Quantitation of bone ingrowth using back-scattered electron imaging disclosed no significant differences in the amount of new bone formed at the graft site between autogenous bone and the ceramic plus autogenous bone recipients (23.4 +/- 10% vs. 25.8 +/- 8.8%) when correction for the autogenous bone volumes was performed. Light microscopic analysis of toluidine blue-stained transverse sections demonstrated new bone growth around and through the ceramic bone graft material. These results suggest that use of a collagen-biphasic calcium phosphate ceramic and autogenous bone mixture (3:1) provides a suitable osteoconductive alternative to the use of autogenous bone and results in the formation of a mechanically competent fusion mass not significantly different from that obtained with autogenous bone alone. PMID- 1613631 TI - Three-dimensional mechanical properties of the thoracolumbar junction. AB - The thoracolumbar junction region is a frequent site of spinal trauma. Accurate knowledge of the normal mechanical behavior of the intervertebral joints in this region is of importance to the clinician in treating the spinal injuries. The present study documented the complete three-dimensional motions of levels T11-T12 and T12-L1 in the thoracolumbar region. Pure moments of flexion/extension, bilateral axial torque, and bilateral lateral bending were applied to 11 three vertebrae human cadaveric specimens (T11-L1) to a maximum of 7.5 Nm. Intervertebral motions were calculated using stereophotogrammetry and presented in the form of load-displacement curves, each containing three rotations and three translations at one intervertebral level. Average +/- SD flexion, extension, axial rotation, and lateral bending ranges of motion to one side were 2.7 +/- 1.3 degrees, 2.4 +/- 1.3 degrees, 1.8 +/- 0.7 degrees, and 3.5 +/- 1.1 degrees, respectively, at level T11-T12. The same ranges of motion at T12-L1 were 2.9 +/- 1.4 degrees, 3.9 +/- 1.4 degrees, 1.2 +/- 0.7 degrees, and 3.7 +/- 1.1 degrees, respectively. The extension and axial rotation ranges of motion at level T11-T12 were found to be significantly different than the same motions at T12-L1. The different geometry in the facet joints explains these observed differences in the mechanical behavior of T11-T12 and T12-L1. PMID- 1613632 TI - The effects of fluoridated water on bone strength. AB - Fluoride from fluoridated water accumulates not only in the enamel of teeth but also in the skeleton. The effects of fluoridated water on the skeleton are not well understood, yet there is some evidence that fluoridated water consumption increases the incidence of fractures. In the present study, femoral bending strength was measured in rats on fluoride intakes that ranged from low levels to levels well above natural high fluoride drinking water. Bone strength followed a biphasic relationship with bone fluoride content. Fluoride had a positive effect on bone strength for lower fluoride intakes and a negative influence on bone strength for higher fluoride intakes. The vertebral fluoride content at which femoral strength was maximum was between 1,100 and 1,500 ppm. The increase in femoral strength at this fluoride level was not accompanied by an increase in femoral bone density. The optimal fluoride content is within the range of bone fluoride contents found in persons living in regions with fluoridated water (1 ppm) for greater than 10 years. PMID- 1613633 TI - Effect of controlled local release of sodium fluoride on trabecular bone. AB - Systemic sodium fluoride has been used in the treatment of osteoporosis. Recent studies have shown that it has a positive risk/benefit ratio for use in increasing spinal trabecular bone density. However, thinning of the cortices of the long bones with a resulting increase in fracture incidence has been observed. This study was designed to determine the response of bone to sodium fluoride released from a biodegradable polymer matrix, a technique which could potentially deliver it locally to a site of need in the skeleton which has a positive response to fluoride. In one group of mature New Zealand white rabbits, cylindrical poly(D,L-lactic acid) (PLA) implants, with or without impregnated sodium fluoride, were implanted into the contralateral femoral trochanters and tibial metaphyses. In a second group, similar implants were placed in adjacent vertebrae. Four weeks postimplantation, the femora, tibiae, and vertebrae were removed, sectioned, cleaned of all but mineralized tissue, and the surfaces of the sections stained. The stained surfaces were imaged and analyzed for morphometric properties of the trabeculae. Comparing contralateral vertebrae, those exposed to sodium fluoride had significantly thickened trabeculae, with decreased spacing between them and a greater bone fraction. A similar increase in trabecular width was found in the subchondral bone of the proximal tibiae exposed to local release fluoride. Femoral sections showed no difference, possibly due to the lack of extensive trabecular bone in the region chosen for study. PMID- 1613634 TI - Nursing assessment of the elderly patient. AB - Assessment, the first phase of the nursing process, is the key factor in identifying a patient's health care needs. This article addresses the special needs of the elderly population and discusses the application of the assessment process to the planning and implementation of patient care. PMID- 1613635 TI - Intravenous therapy for the elder patient: implications for the intravenous nurse. PMID- 1613636 TI - Lost in the system. AB - Today's health care system is not well suited to the needs of the elder patient. The author discusses the dilemmas confronting this patient population, the increase in the size of the elder population, and the changing lifestyles of elders. It is important for all health care practitioners to recognize and understand these issues and assist the elder patient in obtaining quality health care. PMID- 1613637 TI - The role of the nurse as a patient advocate: a call to action. PMID- 1613638 TI - The physiology of aging. PMID- 1613639 TI - Use of deacetylated gellan gum (Gelrite) for the production of sulphamethizole containing beads. AB - Deacetylated gellan gum (Gelrite) was used to produce a bead formulation containing sulphamethizole by a hot extrusion process into chilled ethylacetate. The spherical dried beads recovered had a porous surface which could be reduced in porosity by increasing the Gelrite concentration. Energy dispersive analysis showed the drug to be uniformly distributed throughout the beads. Dissolution studies confirmed that the drug was slowly released from the beads, the retardation of which could be extended by the use of increasing Gelrite concentration or by post-treatment of dried beads with either a waxy sealant or gamma irradiation. In-vivo studies in dogs confirmed that dried beads prepared by extruding a suspension of 10 per cent w/w sulphamethizole in 3 per cent aqueous Gelrite dispersion had effective sustained properties on oral dosing in comparison to a conventional capsule formulation but had a possible small loss in relative bioavailability. PMID- 1613640 TI - Influence of the surface properties of low contact angle surfactants on the body distribution of 14C-poly(methyl methacrylate) nanoparticles. AB - The body distribution of surfactant-coated and non-coated poly(methyl methacrylate) nanoparticles with a size of 131 +/- 30 nm after intravenous injection into rats was investigated. The coating materials were poloxamine 904, poloxamine 908, poloxamine 1508, poloxamer 338, and Brij 35. These materials were preselected by the method of contact angle measurement. No overall valid relation between contact angles and the modification of body distribution could be found. However, the classification of surfactants by determination of the contact angles of the surfactant solution on the polymer material seems to be a very helpful method for preselection of poloxamers and poloxamines. Another parameter for preselection could be molecular weights of the poloxamines. Poloxamine 1508 was the most efficient coating material in reducing the liver uptake and increasing the blood levels of poly(methyl methacrylate) nanoparticles. PMID- 1613641 TI - Influence of drug loading level on drug release and dynamic swelling of crosslinked gelatin microspheres. AB - The effect of drug loading level both on dynamic swelling and drug release was evaluated using crosslinked gelatin microspheres. Owing to water penetration the microsphere diameter went first to a maximum value, which was not affected by the payload; the diameter gradually approached to an equilibrium swollen value, which was affected by drug loading level. Water absorption increases and drug diffusion decreases the microsphere diameter. Obviously, the diameter variation depends on the factor (water absorption or drug diffusion) predominating in the process. As the payload affected only the equilibrium swollen value it is reasonable to hypothesize that drug loading level has a greater effect on drug diffusion than on polymer relaxation. This rationale could explain the increase of the diffusion component of the drug release process as the payload increased. PMID- 1613642 TI - Coating charcoal with polyacrylate-polymethacrylate copolymer for haemoperfusion. I: Fabrication and evaluation. AB - A potential haemoperfusion system has been developed using activated charcoal encapsulated with a polyacrylate-polymethacrylate copolymer. The film forms a coating of great mechanical strength around the charcoal particles, which is readily permeable to water and certain dissolved substances. The charcoal granules were coated with various membrane thicknesses consisting of a 2-10 per cent (by weight) film coat, using the modified method of non-solvent addition of Benita et al. (1985). The effect of various encapsulation variables such as stirring rate, rate of addition of non-solvent, percentage of coating polymer and concentration of a non-wall-forming polymer (PIB) in the non-solvent phase on adsorptivity, as well as the release of fine particles, were determined. The effect of coating thickness on the adsorption rate of the coated charcoal was investigated by constructing Higuchi diffusion model plots using methylene blue as a model adsorbate. It was found that the membrane permeability can be adjusted by changing experimental conditions to obtain high adsorption capacity along with a low level of released particles. Further, the effect of presoaking of the coated charcoal in purified water, normal saline, and 0.067 M phosphate buffer pH 7.4 (for 24 h at 37 degrees C) on the rate of adsorption of methylene blue was also evaluated. PMID- 1613643 TI - Plasticizers and their effects on microencapsulation process by spray-drying in an aqueous system. AB - Microencapsulated theophylline particles were prepared by an aqueous spray-drying process using hydroxypropylmethylcellulose. The effect of different plasticizers, triethylcitrate, polyethylene glycol, propylene glycol, glycerin and citric acid, was investigated. Triethylcitrate, a water-insoluble plasticizer, produced a porous honeycomb-like microcapsule wall resulting in rapid drug release. The presence of the plasticizers also influenced crystallization of the drug. The formation of a solid drug dispersion was observed with the addition of citric acid or glycerin. Changes in the pH of liquid feed caused by the plasticizer had an effect on the product dissolution profile, but this was not a major factor. Formation of pores due to leaching of plasticizers during dissolution enhanced drug release. Flow property measurements indicated that the plasticizers also affect the cohesiveness of the spray-dried products. Compared to the microcapsules formed without any plasticizers, propylene glycol, glycerin and citric acid appeared to be beneficial to the microcapsule wall formation, with microcapsules containing citric acid having the slowest drug release. PMID- 1613644 TI - Microencapsulation of propranolol hydrochloride by the solvent evaporation technique. AB - Propranolol hydrochloride microcapsules were prepared by the coacervation-phase separation induced by solvent evaporation technique. The cellulose acetate phthalate was employed as coating material alone and in combination with ethyl cellulose. The prepared microcapsules were evaluated for their drug content, particle size distribution (microscopic method), flow properties, bulk density, in vitro dissolution and drug release kinetics. PMID- 1613645 TI - A new approach to encapsulating non-steroidal anti-inflammatory drugs. V. Biopharmaceutical study of microcapsules of azapropazone coated with pectin and rutin. AB - Azapropazone was encapsulated with pectin-rutin mixture using the fluidized bed technique. The encapsulated particles showed higher dissolution rate and bioavailability but lower ulcerogenic activity as compared with the drug alone. PMID- 1613646 TI - Polymers for biodegradable medical devices. IX: Microencapsulation studies; effects of polymer composition and process parameters on poly-hydroxybutyrate hydroxyvalerate microcapsule morphology. AB - Reservoir-type microcapsules were prepared using a double emulsion solvent evaporation technique from a series of nine different poly-beta-hydroxybutyrate (PHB)-based polymers in which both molecular weight and hydroxyvalerate content were varied. Particles prepared from a low molecular weight (MW 43,000) homopolymer had a shrivelled appearance, but were not porous. When the molecular weight of the fabricating homopolymer was increased to 540,000, however, these features disappeared and non-wrinkled particles with microporous surfaces were observed. Microcapsules prepared from a high molecular weight copolymer of PHB with 10.8 per cent hydroxyvalerate (HV) had a similar appearance, but particles prepared from a high molecular weight 20.1 per cent HV copolymer had much smoother and less porous surfaces. Lowering the molecular weight of the copolymer had the effect of producing particles that were generally distorted in shape and had highly irregular, macroporous, surface morphologies. Increasing the double emulsion temperature to 40 degrees C at 2 min after phase combination typically generated smoother and/or less porous particles and improved the batch yield. The numerous factors potentially responsible for the development of morphological characteristics of the products are discussed in the light of these observations. PMID- 1613647 TI - Process and formulation variables in the preparation of wax microparticles by a melt dispersion technique. I. Oil-in-water technique for water-insoluble drugs. AB - Ibuprofen-wax (carnauba, paraffin, beeswax, and the semisynthetic glyceryl esters -Gelucire 64/02 and Precirol ATO5) microparticles were prepared without organic solvents as an alternative to polymeric microparticles. In the melt dispersion technique, the drug-wax melt was emulsified into a heated aqueous phase followed by cooling to form the microparticles. The microparticles were characterized with respect to their drug loading, and morphological and release properties. They were spherical and non-agglomerated and drug loading close to 60 per cent were achieved. The more hydrophilic waxes (Gelucire 64/02 or Precirol ATO5) could be prepared without the use of surfactants. With the other waxes, increasing amounts of sodium lauryl sulphate in the external aqueous phase decreased the drug loading because of drug solubilization when compared to the polymeric stabilizer, poly(vinyl alcohol). The type of wax, the rate of cooling, and the temperature of the aqueous phase had no significant effect on the drug loading because of the low solubility of the drug in the external aqueous phase. The drug release was controlled by the hydrophobicity of the wax. Besides ibuprofen, other water soluble drugs (ketoprofen, indomethacin, hydrocortisone) were also encapsulated by this method. The wax microparticles could be formulated into an aqueous sustained-release oral suspension dosage form. PMID- 1613648 TI - An analysis of first-order release kinetics from albumin microspheres. AB - Release rates from BSA microspheres prepared from various conditions are analysed using a previously reported equation expressing the first-order release rate constant. The permeability constants calculated applying the equation on experimental release rates are in good agreement with the constants measured from permeation studies using planar membrane, for various preparation conditions. It is shown that the equation expressing the first-order release rate constant is valid more extensively. The permeability constant varies depending on the preparation conditions, and the reason for variation is shown clearly to be the difference in degree of swelling of the polymer. It was found from regression analysis that there is relatively simple correlation between unknown parameters of the equation and the preparation conditions. Release rate constants can be calculated applying the equation on the known parameters and the estimated values of the unknown parameters from the correlation. Good agreement was found between the calculated values and experimental ones; therefore, at least as far as we examined here, the release rate constant of the microsphere can be estimated from the preparation conditions. PMID- 1613649 TI - Process and formulation variables in the preparation of wax microparticles by a melt dispersion technique. II. W/O/W multiple emulsion technique for water soluble drugs. AB - Pseudoephedrine HCl-carnauba wax microparticles were prepared by a multiple emulsion-melt dispersion technique. A heated aqueous drug solution was emulsified into the wax melt (W/O emulsion), followed by emulsification of this primary emulsion into a heated external aqueous phase (W/O/W emulsion). The drug containing microparticles were formed after cooling and congealing of the wax phase. The encapsulation efficiencies were above 80 per cent and actual drug loadings close to 50 per cent were achieved. The surface of the microparticles had submicron pores and drug crystals were visible on cross-sections. The drug loading depended on the rate of cooling and the volume of the internal aqueous phase but was insensitive to the volume of the continuous phase. The drug release was much faster when compared to the release from polymeric microspheres. PMID- 1613650 TI - Psychodiagnosis of personality structure: psychotic personality organization. AB - Recent developments in Rorschach psychology, including nomothetic approaches focused on scores, ratios, and indices and idiographic approaches focused on content emerging from psychoanalytic theory, offer the Rorschach clinician a rich and potent interpretive methodology. This article examines the structural diagnosis of personality organization with a focus on psychotic personality structure. Rorschach approaches to the differential diagnosis of psychotic personality organization are presented. The Rorschach is viewed as indispensible in the differential diagnosis of personality organization, especially in the so called "borderline" cases. PMID- 1613651 TI - A psychotic gynemimetic: I just had a pregnant thought. AB - Nomothetic and idiographic content analytic approaches to the Rorschach are used in complementary fashion to explore the psychotic personality structure and primitive interpersonal models in a 37-year-old biologically normal male, who was a gynemimetic, that is, a transvestite who aspired to have the genetalia of a woman. The Rorschach was riddled with psychotic verbalizations and imagery suggesting inadequate differentiation from the original symbiosis, inadequate symbiosis anxiety, and significant separation anxiety--a constellation culminating in the transsexual fantasy of fusion with the mother. PMID- 1613652 TI - A psychotic (sexual) psychopath: "I just had a violent thought ...". AB - The case of a 33-year-old White male with a history of sexual assault is presented. His Rorschach is analyzed and interpreted using both psychostructural (Exner, 1986) and psychodynamic (Cooper & Arnow, 1986; Kwawer, 1980; Meloy & Gacono, in press-b) methodologies. Findings are used to understand the presence and interaction of both psychopathic character and psychotic personality organization in this mentally ill, sadistic, and sexually predatory young man. PMID- 1613653 TI - Toward a synthetic approach to the Rorschach: the case of a psychotic child. AB - Much Rorschach research on case material focuses on the utility of a single scoring system, set of variables, or scale in isolation from other systems, scales, or perspectives. This approach fails to acknowledge the complexity of the Rorschach and to reflect the manner in which sophisticated clinicians select and synthesize various perspectives during the clinical inference and decision-making process. A case of a psychotic child is presented to illustrate the utility of a synthetic approach to the Rorschach. The strengths and weaknesses of various Rorschach perspectives in addressing specific diagnostic issues is explored through the case material. PMID- 1613654 TI - Affective differences among empirically derived subgroups of headache patients. AB - We (Kinder, Curtiss, & Kalichman, 1991) reported four distinct subgroups of male and female headache patients based on the results of a cluster analysis of the Minnesota Multiphasic Personality Inventory (MMPI). We extended these results by providing further descriptive information of the subgroups. The MMPIs of 229 (52 males and 177 females), composing the second cohort in our (Kinder et al., 1991) study of headache patients, were reclassified into subgroups. Differences between subgroups on independent measures of anxiety, anger, anger expression, and depression were investigated. Significant differences were found among the empirically derived subgroups. Results are discussed in the context of previous research on headache and back pain patients. PMID- 1613655 TI - Form E of the 16PF and adults with mental retardation: internal consistency and validity. AB - Form E of the Sixteen Personality Factors Questionnaire (16PF-E) was administered to 70 adults (45 men and 25 women) who resided in a public facility for mentally retarded persons. Alpha coefficients were computed for each of 16 primary trait scales. The Intelligence (B), Ego Strength (C), Dominance (E), Superego Strength (G), Parmia (H), Protension (L), Autia (M), Shrewdness (N), Guilt Proneness (O), and Self-Sentiment (Q3) scales exhibited low internal consistency, whereas Premsia (I) and Self-Sufficiency (Q2) evidence relatively higher levels. Personality traits of subjects were also assessed by staff ratings. Ratings were compared to 16PF-E primary and secondary trait scores via correlation coefficients. Results provided virtually no support for the validity of the 16PF E primary scales and the Exvia, Anxiety, and Cortertia secondary factors as applied to the subject population. Limited support for the validity of the Independence secondary factor was found. PMID- 1613656 TI - Establishing a Placement Index for behaviorally disturbed children using the Hand Test. AB - Hand Test variables were evaluated to see if they would empirically discern varying levels of behavioral and social maladjustment in severely behaviorally handicapped children. Hand Test protocols of 6- to 18-year-old students (N = 100) were gathered. Twenty protocols from each of three levels of special education placement were obtained in addition to 40 protocols of students enrolled in regular educational classrooms. A stepwise discriminant analysis yielded both pathology (PATH) and aggression (AGG) as significant discriminators (p less than .05). Cutoff scores and a weighted equation consisting of nine variables was derived using proper placement in group setting as the criteria. The assignment of children to correct placement levels was 64% or 79%, depending on the stringency of criteria. These findings reinforce the utility of the Hand Test as a valuable tool in the psychologist's testing armament for assisting with placement decisions and support the strength of integrating multiple variables to aid with these decisions. Replication of this study for the purpose of cross validation of the Placement Index is strongly encouraged. PMID- 1613657 TI - Revisiting the Rorschach of Sirhan Sirhan. AB - The published Rorschach (Kaiser, 1970) of Sirhan Sirhan, the man who assassinated presidential aspirant Robert F. Kennedy in 1968, was studied. Psychostructural and psychodynamic analyses were conducted using reliable and valid methodology that was unavailable at the time of examination. In contrast to the defense experts at trial who diagnosed paranoid schizophrenia, the data suggest a depressed and suicidal individual organized at a borderline level of personality. Character pathology is hysterical, paranoid, and dependent. When the Rorschach findings are compared to the development history of Sirhan and the behavior around the time of the assassination, the data are somewhat consistent with the theme of psychic trauma, are very consistent with the theme of recurrent loss and pathological mourning, and validate a characterological distrust and hatred of, yet hysterical dependence on, the object world. Rorschach indices of predatory violence (Meloy, 1988a) in relation to the planned and purposeful assassination are also discussed. PMID- 1613658 TI - A conceptual validation study of the texture response on the Rorschach. AB - This study addresses the Rorschach texture response (T). The authors proposed a developmental line incorporating tactile self-soothing functions and tactile aspects of interpersonal closeness and related it to T. It was hypothesized that T would be linearly related to one's reliance on tactile cues cognitively by categorizing objects according to texture and behaviorally by touching and stroking. Subjects were 81 women, between the ages of 18 and 30. The results confirm the notion that T is related to both cognitive and behavioral reliance on tactile cues. It was also hypothesized that high T subjects, more than others, would increase their use of tactile cues and touching when stressed, but this hypothesis was not supported. The results were considered to be consistent with the proposed developmental line but not for differential regression along the line. They also supported T as being related to a tactile mode of information processing. PMID- 1613659 TI - Concordance of the MCMI-II, the MMPI, and Axis I discharge diagnosis in psychiatric inpatients. AB - Discriminant functions of the MMPI and the MCMI-II were compared in a sample of 166 hospitalized psychiatric patients with discharge diagnoses of affective disorder (63), schizophrenia (26), substance abuse (35), and other disorders (42). Of special interest was the comparative diagnostic utility of the two instruments in regards to DSM-III-R Axis I diagnoses. Both tests performed reasonably well in the discriminant function analyses; however, the MCMI-II achieved a somewhat superior overall hit rate with this sample of inpatients (79% to 68%). This difference was tied to greater accuracy of the MCMI-II for identifying the affective disorders group. PMID- 1613660 TI - Clinical validity of a Personality Inventory for Children (PIC) profile typology. AB - We evaluated the validity of a profile typology for the Personality Inventory for Children (PIC), a parent-informant measure of child psychiatric status. For referred children, we studied (a) the convergence of PIC profile types with diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., American Psychiatric Association, 1980) and (b) the incremental validity of the PIC over diagnoses in the prediction of symptom ratings completed by teachers and clinicians. We found a high diagnosis-PIC correspondence only for developmentally disordered children; the overlap for children with emotional conduct problems was poor. For the latter group, however, the correlation of diagnoses with symptom ratings was low, but the incremental validity of the PIC over diagnoses was high. We discuss the use of this profile typology in the clinical evaluation of children and present a case example. PMID- 1613661 TI - The impact of theory on psychological testing: how psychoanalytic theory makes diagnostic testing more enjoyable and rewarding. AB - Systematically applying psychoanalytic theory to psychological testing cultivates a practical, useful, and enjoyable experience of test administration, test scoring, and test interpretation. Furthermore, by grounding psychological testing in psychoanalytic theory, testing becomes rewarding because there is a lively clinical interplay between testing and psychotherapy. These potential sources of enjoyment and skill for the psychological examiner are explored, and several clinical examples are given for illustrative purposes. The need to appreciate the impact of a given theoretical frame of reference is highlighted. PMID- 1613662 TI - Infection of cynomolgus monkeys with a chimeric HIV-1/SIVmac virus that expresses the HIV-1 envelope glycoproteins. AB - Replication competent chimeric viruses that express the gag and pol proteins of SIVmac and the env proteins of HIV-1 were made. One such chimeric virus, SHIV-4, that expresses the vif, vpx, vpr, and nef regulatory genes of SIV and the tat and rev regulatory genes of HIV-1 replicated efficiently in cynomolgus monkeys. This model system can be used to evaluate the efficacy of anti-HIV-1 vaccines directed at the envelope glycoproteins, anti-HIV-1 envelope glycoprotein antiserum or monoclonal antibodies, and anti-HIV-1 drugs designed to inhibit the tat, rev, or env functions. PMID- 1613663 TI - CD4-mimicking antibodies in HIV-positive and normal human sera. AB - An earlier study showed that approximately 5% of HIV-seropositive human sera contain gp120 antibodies that mimic CD4, seen as anti-idiotypic to the CD4 monoclonal T4.2. The present study shows the existence of a second type of CD4 mimicking gp120 antibody, which specifically binds to the CD4 monoclonal, OKT4A. This anti-idiotypic antibody to OKT4A is less frequent than the antibody reacting with T4.2. In two patients studied, this OKT4A binding antibody seems to appear as early during infection as the anti-idiotypic antibody to T4.2; however, the concentration varies more with time. In order to evaluate the possible clinical relevance of these CD4-mimicking antibodies, sera from 208 HIV-seropositive and 204 healthy seronegative individuals were screened. There was a significantly higher frequency of anti-idiotypic antibodies to T4.2 among HIV-positive individuals compared to healthy controls (p = 0.05). However, no correlation was found between the presence of CD4-mimicking antibodies and clinical classification of HIV-infected individuals. PMID- 1613664 TI - Cytokine activation of human macrophages infected with HIV-1 to inhibit intracellular protozoa. AB - Peripheral blood mononuclear cells (PBMCs) from HIV-seronegative donors were infected in vitro with HIV-1. Infection was monitored by cytopathology, supernatant p24 antigen, and by immunocytochemical staining. After 14 days in culture, approximately 70-90% of the cells became infected with HIV, as indicated by cell fusion and immunostaining for virus. At this time, recombinant HuIFN gamma was added to the cultures, followed by infection 24 h later with the intracellular protozoan parasites Toxoplasma gondii, Trypanosoma cruzi, or Leishmania chagasi. Percentages of intracellular parasites were determined at various points thereafter. Using a system capable of detecting both virus and parasite infection, we determined that (a) cells infected with HIV were capable of ingesting and/or being infected by each of these parasitic protozoa, (b) HIV infected macrophages could be activated to inhibit the replication of all three parasites following treatment with IFN-gamma, and (c) cultures of HIV-infected macrophages could respond to IFN-gamma with increased oxidative burst activity. The degree of parasite infection or inhibition observed in infected cells was not significantly different from that observed in non-HIV-infected cells. From these observations, we concluded that HIV-1 infection does not render macrophages unresponsive to IFN-gamma activation for microbicidal activity. PMID- 1613665 TI - One-year follow-up of vaccine therapy in HIV-infected immune-deficient individuals: a new strategy. AB - Immunization of AIDS/ARC patients with autologous cells expressing HIV antigens, although providing clinical and biological benefits, fails to restore cellular immunity. The latter result is due partly to the antiproliferative effect of HIV 1 on activated T-cells (immune suppression), which leads to blockade of specific immune reactions. To overcome immune suppression, a new vaccine strategy was designed consisting of an immunization against HIV-1 combined with components of the T-cell-suppressive (antiproliferative) network. This new vaccine treatment proved to be innocuous in mice, monkeys, and two non-HIV-infected humans. A Phase I clinical trial was performed in six patients previously under cellular immunotherapy and still presenting a cellular immune defect. Preliminary results confirmed, after a 1-year follow-up of the patients, the safety of the new vaccine, which also partially restored the cellular immune response, including anti-HIV HLA-restricted cell-mediated cytotoxicity, delayed hypersensitivity to recall antigens, and proliferation of T-cells specifically activated by recall antigens. PMID- 1613667 TI - Premature mortality related to HIV infection in California 1981-1993. AB - The number of years of potential life lost (YPLL) before age 65 was used to compare the effects of HIV on premature mortality versus other causes of death in California from 1981 to 1993. Using California AIDS case surveillance data, YPLL associated with HIV rose from 629 in 1981 to 120,721 in 1989, and is projected to reach 188,000 in 1993 (plausible range, 155,000-285,000). In 1989, HIV ranked fourth in YPLL behind all malignant neoplasms, traffic-related motor vehicle accidents, and all heart diseases. By 1993, if current mortality trends continue, HIV is projected to be the leading single cause of YPLL in California ahead of all malignant neoplasms (184,597 in 1989), motor vehicle-related YPLL (163,038 in 1989), and all heart diseases. PMID- 1613666 TI - A comparison of younger and older gay men's HIV risk-taking behaviors: the Communication Technologies 1989 Cross-Sectional Survey. AB - Data from the 1989 Communication Technologies cross-sectional survey of gay men in San Francisco indicate that both levels and correlates of sexual risk are different between younger and older gay men. Gay men under the age of 30 report higher risk behavior for human immunodeficiency virus (HIV) infection than do gay men who are 30 years of age or older. Further, the set of correlates of unprotected anal intercourse are different between younger and older gay men. Both young and old gay men report that having a primary partner and a lower perceived impact of the AIDS epidemic on their sexual behavior are associated with risk. However, among young gay men, reporting a lower attributed risk for HIV infection to unprotected anal intercourse, higher concern about AIDS risks, and shorter length of residence in San Francisco are positively correlated with risk-taking behavior. These associations were not statistically significant among gay men 30 years of age or older. It appears that the circumstances and/or reasons for taking sexual risk are different between older and younger gay men. Prevention programs must be designed so that they are sensitive to the needs of each generation of gay men. PMID- 1613668 TI - Prognostic indicators for development of AIDS among intravenous drug users. AB - A cohort of 544 human immunodeficiency virus-1 (HIV-1) seropositive intravenous drug users (IVDUs) was recruited in 1988 and early 1989; data on laboratory markers, clinical symptoms, intravenous drug use, and demographics were collected. Forty-one IVDUs developed AIDS within 2 years of enrollment. Data were analyzed using methods of survival analysis. None of the individuals reported use of antiviral agents or Pneumocystis carinii prophylaxis at baseline. A very strong (p less than 0.001) dose-response relationship was identified between CD4 cell count at baseline and the subsequent development of AIDS. In multivariate analysis, both the presence of more than one clinical HIV-1-related symptom and serum neopterin greater than 12 nmol/L showed significant associations with the relative hazard (95% confidence interval) of AIDS after controlling for CD4 of 2.9 (1.6, 5.6) and 2.0 (1.0, 3.7), respectively. In these IVDUs, serum beta 2 microglobulin did not add predictive power for progression to AIDS. The effect of clinical symptoms was stronger for high CD4 cell counts, indicating the need to monitor HIV seropositive IVDUs with both laboratory studies and clinical evaluation. PMID- 1613669 TI - A model predicting dentists' willingness to treat HIV-positive patients. AB - Data for this study of dentists' willingness to treat HIV-positive (HIV+) individuals were derived from a survey of a probability sample of American general practitioner dentists (GPD). Data were received from 1,351 active GPD, which represented an 88% response rate. Because the outcome measure--willingness to treat HIV+ patients--is dichotomous, i.e., yes/no, logistic regression was selected as the statistical technique to be used for the creation of a predictive model. Seventeen independent variables were initially considered. The final and most parsimonious model contains six independent variables, of which perceived safety in treating HIV+ patients has the most predictive power. Fear of consequences for the practice, if HIV+ patients were seen, was also a powerful predictor, with a sense of ethical responsibility and a past history of treating HIV+ patients also being important predictive variables. Knowledge level about transmission of HIV and concern about risks associated with treating homosexuals were also significant. PMID- 1613670 TI - Human immunodeficiency virus DNA copies as a virologic marker in a clinical trial with beta-interferon. AB - The number of human immunodeficiency virus (HIV) DNA copies in peripheral blood mononuclear cells (PBMC) was quantitated by the polymerase chain reaction (PCR) and used as a virologic marker in a clinical trial with beta-interferon (beta IFN) (6 x 10(6) IU/day administered intravenously for 4 weeks). In 11 HIV infected patients who were clinically stable, the number ranged from 10 to 1,063 copies per 10(5) PBMC. However, percent change of the number in the individual untreated patients stayed between -46.2% and 203.0% of the basal level by one month interval. In six patients who were treated with beta-IFN, changes in the number were not significant before and after the trial. PMID- 1613671 TI - Physicians' attitudes toward assisted suicide in AIDS. AB - We investigated factors influencing attitudes and practices among San Francisco physicians toward physician-assisted suicide in the context of AIDS. To explore this topic a questionnaire was developed for use in comparing two physician groups. This self-administered instrument was completed by 69 physician members of the San Francisco County Community Consortium (CCC), a community-based clinical research organization whose members care for persons with human immunodeficiency virus (HIV) disease. A comparison group consisted of 86 randomly sampled San Francisco physicians recruited from the California Medical Association mailing list. Anonymity of respondents was maintained. Chi-squares and t-tests were conducted to compare physician groups with regard to demographics and experiences with AIDS. Factor analytic techniques and correlational analyses were used to identify attitudinal and behavioral predictors of willingness to assist in a patient suicide. Twenty-three percent of the total sample would be likely to grant the patient's initial request for assistance in committing suicide. When faced with an adamant request, CCC members would be more likely to assist than comparison group physicians. Ethical beliefs were the strongest predictor of physicians' intention to assist. Identification with the AIDS patient also had significant predictive value. PMID- 1613672 TI - B-cell activation and differentiation by HIV-1 antigens among volunteers vaccinated with VaxSyn HIV-1. AB - The generation of memory B cells in response to vaccination with a baculovirus derived recombinant gp160 candidate AIDS vaccine, VaxSyn HIV-1, was investigated in 12 healthy human volunteers who were immunized with VaxSyn HIV-1, hepatitis B vaccine, or alum adjuvant alone on days 1, 28, 180, and 540. Peripheral blood mononuclear cells were collected pre- and post-immunization and cultured unstimulated or with pokeweed mitogen (PWM), VaxSyn HIV-1 (rgp160), or HIV-1 lysate (iHIV-1) for 7 days before polyclonal and HIV-1-specific IgG production in culture supernatants (SNs) were measured. No differences were seen in the spontaneous or PWM-induced IgG production in SN from vaccinees and controls. Only vaccinee SN contained higher-than-normal levels of polyclonal IgG after stimulation with either rgp160 or iHIV-1, especially after the second and third booster immunizations on days 180 and 540, respectively. There were also contemporaneous increases in HIV-1-specific antibody in SN of all vaccinees, albeit at different time points throughout the study. We conclude that VaxSyn HIV 1 induces antigen-specific B-cell responses with the generation of memory B cells in vivo that can be reactivated in vitro to deliver an anamnestic response. PMID- 1613673 TI - Adjunctive corticosteroid therapy for Pneumocystis carinii pneumonia in AIDS: a randomized European multicenter open label study. AB - Fifty-nine human immunodeficiency virus type-1-infected patients with a microscopically proven first episode of moderate to severe Pneumocystis carinii pneumonia (PCP) were enrolled into a randomized European multicenter study. The effect of adjunctive corticosteroid (CS) therapy was assessed on (a) survival to discharge, (b) need for mechanical ventilation, and (c) survival at day 90. CS was given within 24 h of standard therapy as intravenous methylprednisolone 2 mg/kg body weight daily for 10 days. All patients received cotrimoxazole as standard treatment. Inclusion criteria were a PaO2 less than 9.0 kPa (67.5 mm Hg) and/or a PaCO2 less than 4.0 kPa (30.0 mm Hg) while breathing room air. During the acute episode of PCP, 9 (31%) of the 29 control patients died versus 3 (10%) of the 30 CS patients; p = 0.01. Mechanical ventilation was necessary in 15 patients; 12 (41%) in the control group and 3 (10%) in the CS group; p = 0.01. The 90-day survival was 69% in controls versus 87% in CS patients; p = 0.07. Based on these data we conclude that adjunctive CS therapy for moderate to severe PCP in AIDS patients reduces the acute mortality and the need for mechanical ventilation. PMID- 1613674 TI - Influence of treatment with zidovudine (ZDV) on the long-term survival of AIDS patients. AB - The influence of treatment with zidovudine (ZDV) and other factors on long-term survival of AIDS patients was analyzed in a cohort of 629 adults. A total of 434 (69%) were diagnosed before ZDV became routinely available in Spain (December 1987) or refused the drug, while the remaining 195 (31%) received ZDV (starting at a dose of 750-1,200 mg/day). A total of 412 (65.5%) were parenteral drug addicts and 217 (34.5%) male homosexuals. Two hundred thirty-two (36.9%) presented with a tuberculosis, 303 (48.2%) with other opportunistic infections, 69 (11%) with Kaposi's sarcoma, and the remaining 25 (4%) with a lymphoma. By December 1990, 251 (39.9%) of the 629 have already died with a cumulative survival probability of 50.6% after 2 years (45.3-55.9%; 95% confidence interval). When patients receiving ZDV were compared with those untreated, the estimated survival probability was significantly (p less than 0.0001) higher (89% vs. 59% after 1 year, 69% vs. 48% after 2 years, and 55% vs. 40% after 3 years). Moreover, treatment with ZDV (p less than 0.0001) together with being less than 45 years old (p less than 0.0001), being a parenteral drug addict (p = 0.016), and presenting with tuberculosis (p less than 0.0001) were the factors selected by the multivariate analysis as independently improving the prognosis. In conclusion, adult AIDS patients (homosexual or drug addicts) may benefit from treatment with ZDV, at least during 3 years. PMID- 1613675 TI - HTLV-I and HTLV-II infection in Uruguay. PMID- 1613676 TI - Clinical characteristics of male homosexual/bisexual HIV-infected prison inmates. PMID- 1613677 TI - Influence of gender, age, and transmission category on the progression from HIV seroconversion to AIDS. PMID- 1613678 TI - Nimodipine in acute alcohol withdrawal state. AB - The effect of the calcium channel blocker, nimodipine, in acute alcohol withdrawal was investigated in a randomized, placebo controlled, double blind study. Thirty-two male patients with a history of alcohol dependence according to DSM-III criteria, but no other substance abuse, were included. A new rating instrument which fulfilled theoretical test criteria was applied to determine the severity of the alcohol withdrawal state. The patients received nimodipine or a placebo on four separate occasions (4 x 60 mg) and, in addition, clomethiazole, according to a standardized procedure. Our investigation has shown that, in the first 48-72 h of alcohol withdrawal, both groups consumed similar amounts of additional clomethiazole medication. Thus, no significant effect of nimodipine on the acute alcohol withdrawal state could be demonstrated. There was some tendency for nimodipine to ameliorate psychosensory dysfunction. PMID- 1613679 TI - Leukocytosis, monocytosis and neutrophilia: hallmarks of severe depression. AB - To date, there has been a small number of reports that severe depression is accompanied by disturbances in total white blood cell (i.e. leukocytosis) and leukocyte subset (i.e. neutrophilia, monocytosis, lymphopenia) counts. These results, however, have not yet been validated in a large-scale, well-controlled study. To this end, we have counted the number of leukocytes, monocytes, lymphocytes and granulocytes (neutrophils, eosinophils, basophils) in 22 healthy controls and in 109 depressed inpatients. We noted leukocytosis in major depressed patients compared with normal subjects, whilst minor depressives manifested intermediate findings. Leukocytosis was significantly more pronounced in major depressed males compared with major depressed females. Major depression related leukocytosis appears to be characterized by neutrophilia and monocytosis. There was a significant positive relationship between the overall severity of illness on one hand, and the degrees of leukocytosis, neutrophilia and monocytosis on the other. The total number of both phagocytic cell populations (i.e. monocytes and neutrophils) was significantly and positively related. Our results might point to the existence of an inflammatory process in major depressed subjects, particularly in males. PMID- 1613680 TI - Ascertaining psychiatric diagnoses with the family history method in a substance abuse population. AB - Research investigating patterns of familial aggregation of psychiatric disorders has used the family history method in which a single family member reports on the psychiatric history of their relatives. This method is more efficient and less costly than the family study method, in which direct interviews are performed on as many family members as possible. The family history method has been shown to have good specificity, in family studies of depression, but sensitivity has been less acceptable. The present study is the first study to report on the sensitivity and specificity of five psychiatric diagnoses made in a substance abusing population using the family history method. Among substance abusers and their family members, substance abuse is the most accurately diagnosed disorder. However, among family members only, the accuracy of diagnosing substance abuse declines significantly. Spouses and offspring are better informants than parents or siblings, and female relatives are better informants than male relatives. When more than one informant is available and positive diagnoses are determined by any positive family report, sensitivity for most disorders increases significantly. The results are discussed in terms of increasing the accuracy of the family history method. PMID- 1613681 TI - Behavioral contagion in sibships. AB - A behavior is "contagious" if one person is more likely to exhibit it when a relevant other person has already done so. In this sense, behavioral contagion is commonly thought to contribute to many social problems, such as drug abuse and teenage promiscuity. In this paper we focus on behavioral contagion in sibships. Borrowing a model from the theory of contagious diseases, we show that contagion will cause prevalence to increase with sibship size. This model also allows us to estimate the magnitude of the contagious factor relative to non-contagious factors. Finally, we develop two statistical tests for the presence of contagion. Results are presented for participation in a skill-development program and four child-psychiatric conditions: neurosis, hyperactivity, somatization, and conduct disorder. Evidence is presented that program participation is probably contagious and conduct disorder possibly so. The other three child-psychiatric conditions are shown not to be contagious. Implications for research and practice are discussed. PMID- 1613682 TI - Midazolam shortens seizure duration following electroconvulsive therapy. AB - In an open, prospective clinical trial, midazolam anaesthesia was compared with thiopental (plus suxamethonium chloride as a muscle relaxant) to clinically evaluate the former as an anaesthetic and a muscle relaxant during electroconvulsive therapy (ECT). Twelve depressed patients underwent a course of ECT, receiving midazolam or thiopental anaesthesia alternatively. Significant differences were found in seizure duration between the two anaesthetics. Midazolam shortened the seizures to a duration that was not therapeutically desirable. There were no differences in stimulus parameters between the two groups. The muscle relaxant effect of midazolam failed to provide optimal paralysis. Thus, midazolam anaesthesia offers no advantage over standard anaesthetic agents for ECT. PMID- 1613683 TI - Therapy through art. Facilitating treatment of sexual abuse. AB - 1. Infants and preverbal children encode memory through visual and sensorimotor channels, and there is evidence that at times of intense stress and terror, the cognitive memory system may be bypassed in all age groups. 2. Art therapy offers visual and sensorimotor media that may more easily allow repressed traumatic memories to surface. 3. Art therapy is often used with children and adolescents to overcome resistance, build trust, reduce tension, and stimulate memory. It may also be useful in working with adults, because the repression occurred at a much earlier developmental stage, the adult may also have a child's concept of the traumatic event. PMID- 1613684 TI - Normal pressure hydrocephalus. A potentially reversible form of dementia. AB - 1. Normal pressure hydrocephalus (NPH) is a rare but potentially treatable form of dementia. Shunting will improve functioning in 40% to 50% of patients. 2. The classic symptoms of NPH are dementia characterized by mild memory impairment and apathy, ataxic gait, and urinary hesitancy or incontinence. 3. The patient with NPH may present with psychiatric symptoms of depression, paranoia, visual hallucinations, irrational hostility, and aggression or mania. 4. Patients with NPH are indifferent about activities of daily living and personal safety and require close supervision. PMID- 1613685 TI - Traumatic war. Stress & schizophrenia. AB - 1. An examination of the effects of the Lebanese war on the citizens found that traumatic war events can be regarded as of primary importance for risk factors triggering the onset of schizophrenia. 2. The overall findings indicate an increase in the rate of admission for men diagnosed with schizophrenia throughout the 12 years of the war. The most significant increases occurred either following intensive fighting episodes or months later due to the additive effect of stress. 3. How soon individuals are affected by environmentally induced war stress may be related to their level of vulnerability to the disorder. PMID- 1613686 TI - Xanax: pros and cons. PMID- 1613687 TI - Confessions of a geriatric nurse researcher. PMID- 1613688 TI - Bottom line. PMID- 1613689 TI - Where assault begins. PMID- 1613690 TI - Psychiatric triage: a cost-effective approach to quality management in mental health. AB - As seen from this trial program, psychiatric triage in the ED is potentially a very effective tool for improving the quality of mental health patient care. For a minimal investment in personnel, there is a potential for a major improvement in patient care, patient record documentation, interdepartmental relations, and financial reimbursement to the institution. PMID- 1613691 TI - How to reduce the risk of HIV infection for the seriously mentally ill. AB - 1. The professional literature increasingly indicates the need to educate persons with serious mental illness regarding HIV/AIDS. 2. Community-based organizations currently responding to the AIDS epidemic are poorly equipped to respond to the special needs of persons with serious mental illness. 3. Persons with serious mental illness are concerned by HIV/AIDS. Some, however, will incorporate education into their pathology via delusional systems or misunderstandings. 4. Effective programs for this population can be developed following community health nursing principles. PMID- 1613692 TI - Steroids in rheumatoid arthritis: the honeymoon revisited. PMID- 1613693 TI - Microfocal radiography with macroradiographs in osteoarthritis--does it hit the spot and show the big picture? PMID- 1613694 TI - Why everything (or nothing) seems to work in the treatment of scleroderma. PMID- 1613695 TI - Inhibition of type II collagen induced arthritis in mice by an immunosuppressive extract of Tripterygium wilfordii Hook f. AB - The effects of Tripterygium wilfordii Hook f (TWHf), a Chinese herbal remedy, on type II collagen induced arthritis (CIA) in DBA/1LacJ mice were determined. Mice were divided into 4 groups receiving oral treatment for 63 days: Group A, sham feedings; Group B, TWHf (78 mg/day); Group C, TWHf (140 mg/day); Group D, TWHf (140 mg/day) starting 21 days after collagen immunization. Arthritis incidence was reduced and day of onset delayed in Groups B and C compared with A. Arthritic joint counts, arthritic severity scores, and anticollagen antibody titers were decreased in Groups B, C, and D compared with A. Histopathology revealed destructive arthritis only in Group A. Our results indicate that TWHf is a potent immunosuppressive inhibitor of CIA, even when treatment is begun 3 weeks after immunization. PMID- 1613696 TI - Polyamine levels in synovial tissues and synovial fluids of patients with rheumatoid arthritis. AB - We determined the polyamine contents of the synovial tissues from 11 patients with rheumatoid arthritis (RA), and the free putrescine levels in the synovial fluids (SF) from 10 patients with RA, 7 with osteoarthritis (OA), 5 with posttraumatic arthritis, and 3 with infectious arthritis. Putrescine levels in the synovial tissues correlated with serum C reactive protein concentration in patients with RA. Free putrescine levels in SF were significantly elevated in patients with infectious arthritis, compared with those found in RA, OA, and posttraumatic arthritis. Free putrescine levels in SF from patients with RA were significantly higher than in those with OA. Our findings suggest that polyamines may play an important role in RA. PMID- 1613697 TI - c-myc mRNA expression in minor salivary glands of patients with Sjogren's syndrome. AB - c-myc protooncogene is implicated in the pathogenesis of B cell lymphoid malignancies and high levels of c-myc mRNA expression are observed in activated blood mononuclear cells. Sjogren's syndrome (SS) is characterized by lymphocytic infiltrates of exocrine glands, remarkable B cell hyperreactivity and a strong predisposition to B cell neoplasia. In this study, c-myc protooncogene mRNA expression in 29 labial minor salivary gland biopsies from patients with primary SS and 15 controls was examined using in situ hybridization histochemistry. Two 40mer oligonucleotides from the 1st and the 2nd exon of the c-myc gene, labeled with 35S, were used as probes. To detect the origin of the cell hybridized with a c-myc probe, a combined immunochemistry in situ hybridization histochemistry technique was used. High c-myc mRNA expression was detected on acinar epithelial cells. c-myc did not correlate with c-fos and c-jun protein expression. Stronger c-myc mRNA expression was detected in labial salivary glands of patients with longer disease duration (p less than or equal to 0.002) and more intense T lymphocyte infiltrates (p less than 0.05) although these patients revealed no hypergammaglobulinemia. No correlation was observed between c-myc mRNA and B lymphocyte monoclonicity or lymphoma. In conclusion, strong c-myc mRNA expression was observed on epithelial cells of labial salivary glands from patients with primary SS. Our findings may indicate the presence of a reactivated virus hosted in these cells. PMID- 1613698 TI - Life table analysis of 879 treatment episodes with slow acting antirheumatic drugs in community rheumatology practice. AB - In 596 patients with RA managed over a decade in a community practice setting, 879 slow acting antirheumatic drug (SAARD) treatment episodes were analyzed using 5-year life tables. The probability of continuation of therapy was 50% by 9-24 months for all drugs except for methotrexate (MTX), which was 62% by 5 years [corrected]. MTX treatments were of significantly longer duration than those of all other SAARD (p less than 0.001); terminations for both inefficacy (p less than 0.001) and toxicity (NS) were less likely. These findings concur with recent evidence suggesting that MTX is a superior SAARD in this setting. PMID- 1613699 TI - Illness intrusiveness in rheumatoid arthritis: differential impact on depressive symptoms over the adult lifespan. AB - Depressive symptoms in rheumatoid arthritis (RA) were hypothesized to derive from illness intrusiveness--illness-induced lifestyle disruptions. Differences over the adult lifespan were also investigated in 110 outpatients with RA, aged 24-78 years who completed standardized psychological tests. A significant Age x Illness Intrusiveness interaction indicated that depressive symptoms intensified more sharply among comparatively younger vs older individuals as the intrusiveness of RA increased. We conclude illness intrusiveness is an important determinant of depressive symptoms in RA. However, its impact may vary over the course of adult psychological development. PMID- 1613700 TI - A double blind placebo controlled trial of recombinant tissue plasminogen activator in the treatment of digital ischemia in systemic sclerosis. AB - The treatment of digital ischemia in systemic sclerosis remains inadequate. We report a double blind, placebo controlled trial of recombinant tissue plasminogen activator (rtPA), a potent thrombolytic agent. Ten patients received rtPA. A potent, acute fibrinolytic effect was observed. During the infusion of rtPA, improvements in skin blood flow were seen. These improvements were shortlived. PMID- 1613701 TI - Hypersensitivity vasculitis and Henoch-Schonlein purpura: a comparison between the 2 disorders. AB - Leukocytoclastic vasculitis of small vessels and predominant involvement of the skin are common features of both hypersensitivity vasculitis (HV) and Henoch Schonlein purpura. In a study comparing 93 patients with HV and 85 patients with Henoch-Schonlein purpura we found major differences with respect to frequencies and type of organ involvement (gastrointestinal tract, kidneys, skin and joints) which were present in both younger and older patients when analyzed separately. To investigate which clinical criteria best differentiate between these 2 vasculitides, 2 methodologies were employed. A rule requiring 3 or more criteria to be present from a list of 6 yielded 87.1% of correctly classified Henoch Schonlein purpura cases; and 2 or fewer criteria from the same list of 6 correctly classified 74.2% of HV cases. A classification tree was associated with respective values of 83.5 and 84.9%. The results indicate that HV and Henoch Schonlein purpura are similar but separable clinical syndromes. PMID- 1613702 TI - The absence of factor B activation products in scleroderma. AB - Previous investigators have reported the presence of complement activation products in scleroderma. Using an assay consisting of isoelectric focussing followed by immunofixation (IEF/IF) for alternative pathway activation product Ba, and an ELISA for C3d that we developed for evaluating lupus plasmas, we assayed 48 plasmas from patients with diffuse cutaneous scleroderma, 16 patients with the limited CREST variant, 2 patients with mixed connective tissue disease (MCTD) and 4 patients with Raynaud's disease. Ba was not detected in any patient's plasma. Only one plasma from a patient with CREST contained elevated levels of C3d. We cannot reconcile the absence of B activation products in our patients with scleroderma with the results of the previous report, and conclude that further studies are necessary. PMID- 1613703 TI - Brain pathology in systemic lupus erythematosus. AB - Brain pathology was documented in 10 patients with systemic lupus erythematosus (SLE), 7 of whom had clinical neuropsychiatric SLE prior to death. This was manifested by seizures (5 patients), organic brain syndrome (3 patients) and psychosis (2 patients). Multifocal cerebral cortical microinfarcts, associated with microvascular injury, were documented in 4 patients and in our study constituted the predominant histopathologic abnormality attributable to SLE. Changes of a healed vasculitis in medium sized leptomeningeal vessels were seen in 1 case. Agreement between the clinical and pathologic classification of neuropsychiatric SLE was observed in 7/10 (70%) cases and the strongest association was between the presence of cerebral microinfarcts and seizures (4/5 patients, p less than 0.05). No correlation was observed with anticardiolipin, anti-P, lymphocytotoxic and antineuronal antibodies. PMID- 1613704 TI - Bone marrow IgA and IgA subclass synthesis in ankylosing spondylitis. AB - To investigate the source of increased production causing elevation of serum immunoglobulin A (IgA) in ankylosing spondylitis (AS) we studied the production of IgA and IgA subclasses in cultures of bone marrow cells as well as the relative numbers of IgA and IgA subclass containing bone marrow cells obtained from 24 patients with AS and 22 healthy control individuals. In patients with AS serum levels of IgA, IgA, and IgA2 were significantly higher compared to controls. The IgA1 subclass in patient's serum contributed significantly less to the total IgA compared to controls. In bone marrow cultures of patients with AS and controls the production of IgA, IgA1 and IgA2 were in the same range as were the relative numbers of bone marrow cells containing IgA and IgA subclasses. However, the immunoglobulin synthesis by bone marrow cells of patients with AS showed a significant shift towards IgA1 compared to controls. Our findings indicate that the regulatory abnormalities of IgA production in AS involve both the IgA1 and IgA2 subclass and suggest that an abnormal mucosal immune response could be responsible for chronic overproduction of IgA and the elevation of serum IgA in patients with AS. PMID- 1613705 TI - Combination of cyclosporine A and calcitriol in the treatment of adjuvant arthritis. AB - We investigated combination treatment with cyclosporine A (CsA) and calcitriol (CT), 2 immunomodulatory agents, in vivo in the adjuvant arthritis (AA) model in rats. Treatment initiated at priming with complete Freund's adjuvant consisted of daily administration of CsA and CT during the prearthritic phase (14 days). CsA given alone delayed the onset of the disease, whereas the severity was either not affected or paradoxically enhanced. Injection of CT alone reduced the severity of arthritis. The association of low doses of CsA (5 mg/kg) and CT (0.2 micrograms/kg) further delayed the onset of AA and abolished the aggravating effect. Our findings suggest that low doses of CsA and CT in association exhibit the additive beneficial effects of either agent alone. PMID- 1613706 TI - Transient migratory osteoporosis: a variant of reflex sympathetic dystrophy? Report of 3 cases and literature review. AB - Three cases of transient migratory osteoporosis treated with sympathetic blocks are described. Review of the literature in conjunction with the presentation and treatment of these 3 cases led to the formulation of a hypothesis of a common mechanism (mediated through the sympathetic nervous system) responsible for the profound osteoporosis and pain of reflex sympathetic dystrophy and transient migratory osteoporosis. Arguments are presented supporting transient migratory osteoporosis as a variant of the classical reflex sympathetic dystrophy. PMID- 1613707 TI - von Willebrand factor antigen in hypertrophic osteoarthropathy. AB - Recent evidence suggests that a key feature in the pathogenesis of hypertrophic osteoarthropathy (HOA) is an enhanced local platelet vessel wall interaction in the affected extremities. In our investigation we measured plasma levels of von Willebrand Factor Antigen (vWF:Ag; ELISA assay), a marker of platelet and/or endothelial activation, in 5 patients with the primary form of HOA and in 6 patients with the secondary form (due to cyanotic heart disease). Seven subjects matched for sex and age were used as controls. Patients showed statistically significantly higher levels of vWF:Ag in the primary (163.8 +/- 13.9%) and secondary form (152.6 +/- 9.6%, p less than 0.001 for both) when compared to controls (100.4 +/- 6.3%). Our results support the notion that platelet endothelial cell interaction may play a key role in the development of HOA. PMID- 1613708 TI - Control and "fibrositic" tenderness: comparison of two dolorimeters. AB - It can be as important to quantify lack of tenderness, as tenderness. Palpation detects tenderness only; dolorimeters with a limited scale restrict ability to assess variations in thresholds at clinically nontender sites. Such variations must be measured if we are to evaluate generally acting factors affecting tenderness. We measured thresholds at "fibrositic" and control sites in 8 subjects, using 2 observers and 2 different dolorimeters. The traditional Chatillon dolorimeter yielded twice as many readings off the 9 kg scale (17 of 96 versus 8 of 96) as the Fischer instrument, with a scale of 11 kg [continuity corrected (chi 2 = 3.725, p = 0.086)/bd. The Fischer instrument also used a footplate with a smaller diameter, and results using the 2 instruments were not parallel. Median values were the same (5.1 kg), but the Fischer instrument gave lower readings at tender sites (10th percentile 2.4 versus 2.9 kg) and higher values at nontender sites. Thresholds at fibrositic and control sites were significantly correlated, reinforcing evidence of generally acting factors affecting tenderness. PMID- 1613709 TI - Tidal irrigation versus conservative medical management in patients with osteoarthritis of the knee: a prospective randomized study. Tidal Irrigation Cooperating Group. AB - To determine the efficacy of tidal knee irrigation for knee pain due to osteoarthritis (OA), we conducted a randomized, single blind, 14-week prospective trial comparing medical management with tidal knee irrigation in 77 patients with non-end stage OA of the knee and unilateral pain refractory to standard medical treatment. Fifty-seven patients completed the study. Statistically significant differences (p less than 0.05) favoring tidal knee irrigation over medical management were pain after 50' walk, pain after 4-stair climb, most intense pain in previous day, frequency of knee stiffness with inactivity, days of morning knee stiffness in previous week, physician assessment of knee tenderness and overall assessments of therapy effectiveness by both patient and physician. Tidal knee irrigation results in more favorable improvement of pain due to OA than can be accomplished with traditional medical management. PMID- 1613710 TI - A comparison of five preparations of synthetic monosodium urate monohydrate crystals. AB - We conducted preliminary crystallographic investigations and biologic studies on 5 synthetically grown preparations of monosodium urate monohydrate (MSUM) crystals including one preparation of urate spherulites. The 5 crystal preparations exhibited wide variations in morphology, size, surface area, and ultrastructure, but only a few changes in their biologic effects. When injected intraarticularly, urate spherulites were less phlogistic than most acicular forms. Since crystal-cell interactions and inflammatory responses are influenced by crystal size, morphology, and surface characteristics, standardization of methods of preparing MSUM crystals is, therefore, important, particularly when analyzing and comparing results from different research laboratories. PMID- 1613711 TI - Relationship between joint space width and subchondral sclerosis in the osteoarthritic hand: a quantitative microfocal radiographic study. AB - Measurement of joint space width and subchondral sclerosis from x 5 macroradiographic examination of 32 patients with osteoarthritis (OA) of the hand over an 18-month period showed that joint space loss was symmetrical in both hands. Its change showed that over a period of time narrowing progressed proximally from distal interphalangeal to proximal interphalangeal, metacarpalphalangeal and wrist joints. Sclerosis was greatest in those joints at which the largest forces were exerted across the hand in precision, power and pulp-pinch grip, respectively. Our findings suggest that constitutional factors determine the onset of cartilage changes in OA which in turn result in subchondral sclerosis, the extent of which is determined by the pattern of normal forces within the hand. PMID- 1613712 TI - POEMS syndrome in systemic lupus erythematosus. AB - POEMS syndrome [plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal (M) protein, skin changes] although mimicking the connective tissue diseases in several ways has not been reported in a patient who also meets criteria for the diagnosis of systemic lupus erythematosus (SLE). We describe a patient with POEMS syndrome and SLE and review the similarities and differences between POEMS syndrome and other connective tissue disorders. PMID- 1613713 TI - Trimethoprim-sulfamethoxasole induced meningitis in systemic lupus erythematosus. AB - Most reports of drug induced meningitis in systemic lupus erythematosus (SLE) have implicated ibuprofen. We describe a 46-year-old woman with SLE who developed aseptic meningitis abruptly after ingesting trimethoprim-sulfamethoxasole (TMP SMX). This patient had received TMP-SMX twice before; each was associated with increasingly severe reactions, whose relationship with the use of TMP-SMX became apparent only in retrospect. A history of medication use should be sought in all patients with meningitis who have an underlying autoimmune disorder. PMID- 1613714 TI - Multiple complications of the antiphospholipid syndrome with apparent response to aspirin therapy. AB - We describe a patient with antiphospholipid antibodies who presented with a rapid progression of hemolytic anemia, thrombocytopenia, central retinal vein thrombosis, 2 cerebral thromboses and pulmonary hemorrhage. She was treated with high dose prednisolone, plasma exchange, high dose intravenous immunoglobulin and began taking cyclophosphamide without evidence of control of disease. However, the anemia and thrombocytopenia appeared to respond rapidly to low dose aspirin and she made a complete recovery without any further complications. PMID- 1613715 TI - Fever, hepatitis and acute interstitial nephritis in a patient with rheumatoid arthritis. Concurrent manifestations of azathioprine hypersensitivity. AB - We describe a patient with rheumatoid arthritis (RA) who developed hypersensitivity after 3 weeks of therapy with azathioprine with fever, jaundice and renal insufficiency. A percutaneous liver biopsy was compatible with hypersensitivity hepatitis. During azathioprine rechallenge, the symptoms recurred within a few days, consistent with the diagnosis of an acute hypersensitivity reaction. This report is the first to describe the association of an azathioprine induced hypersensitivity simultaneously involving the liver and the kidneys, in the same patient with RA, with resurgence after rechallenge. PMID- 1613716 TI - A patient with Werner's syndrome and osteosarcoma presenting as scleroderma. AB - Werner's syndrome (WS) is often mistaken for scleroderma. We describe a patient with WS who presented with an enlarging, painful mass of the right knee that proved to be a juxtaarticular osteosarcoma of the distal femur. Recognition of WS and prompt investigation of any painful, enlarging masses to exclude sarcomatous degeneration will benefit these patients. PMID- 1613717 TI - Concurrent Sweet's syndrome and erythema nodosum: a report, world literature review and mechanism of pathogenesis. AB - Sweet's syndrome (acute febrile neutrophilic dermatosis) and erythema nodosum are reactive dermatoses whose pathogenesis is currently undefined. Although there are several associated conditions that both of these disorders have in common, the appearance of Sweet's syndrome and erythema nodosum in the same person is rare. Only 8 individuals with biopsy confirmed lesions of both dermatoses were described in the world literature. We describe a 30-year-old woman with biopsy confirmed lesions of Sweet's syndrome on her hand and erythema nodosum on her legs. She had been taking an oral contraceptive and an appetite suppressant during the 5 months before these dermatoses appeared. Both cutaneous lesions rapidly responded to topical corticosteroid ointment and have not recurred since her medications were discontinued. The association of Sweet's syndrome and erythema nodosum is reviewed, their similarities discussed, and a pathogenesis is proposed. PMID- 1613718 TI - A rare case of bronchial stenosis in Wegener's granulomatosis. Dramatic response to intravenous cyclophosphamide and oral cotrimoxazole. AB - We describe a patient with Wegener's granulomatosis (WG) who developed as the only pulmonary manifestation a severe proximal bronchial stenosis despite conventional treatment with steroids and oral cyclophosphamide. The patient subsequently responded to a combined therapy with intravenous (IV) cyclophosphamide and oral cotrimoxazole. We stress the rarity of bronchial involvement in WG and discuss the role of IV cyclophosphamide and cotrimoxazole in the management of this disease. PMID- 1613719 TI - Cryoglobulins, anticardiolipin antibodies and livedo reticularis. PMID- 1613720 TI - Accelerated hypertension in a patient with mixed connective tissue disease. PMID- 1613721 TI - The association of plasma exchange synchronized with intravenous gamma globulin therapy in severe intractable polymyositis. PMID- 1613722 TI - Response to intravenous cyclophosphamide treatment in lupus myelopathy. PMID- 1613723 TI - Fibromyalgia and sex hormones. PMID- 1613724 TI - Articular indices for use in clinical trials of rheumatoid arthritis. PMID- 1613725 TI - Who's sign? PMID- 1613726 TI - Western blotting for the diagnosis of Borrelia burgdorferi infection in patients with sacroiliitis. PMID- 1613727 TI - Rheumatoid arthritis: current concepts and future directions. Proceedings of the 4th Edward Dunlop International Symposium. Montreal, Canada, May 23-25, 1991. PMID- 1613728 TI - Mechanisms of action of disease modifying antirheumatic drugs. AB - The relationship between the biologic activities of disease modifying antirheumatic drugs (DMARD) and their therapeutic effects are complex. Some DMARD are prodrugs, e.g., azathioprine; others may act in combination with endogenous substances, e.g., D-penicillamine and copper salts. Gold compounds, antimalarials, sulfasalazine, azathioprine and methotrexate affect various phagocytic cell functions. Most DMARD inhibit the immune responses of monocytes and of T and B lymphocytes. Gold, sulfasalazine, D-penicillamine also affect fibroblast and/or endothelial cell proliferation. Many DMARD inhibit responses to, or production of, cytokines. Several DMARD have overlapping biologic effects but differ in their therapeutic efficacy in individual patients for unknown reasons. PMID- 1613729 TI - What a rheumatologist needs to know about T cell receptor structure and function. AB - By understanding normal immune response, it has been possible to develop therapeutic strategies toward the treatment of autoimmune disease. The association of autoimmune disease with the major histocompatibility complex (MHC) class II gene products suggests that the inductive events in which the putative autoantigen is presented on the surface of antigen presenting cells in the context of the MHC class II gene products and is recognized by CD4(+) helper or inducer T cells form an interesting target for immunotherapeutic intervention. By understanding the structure/function relationships of T cell receptors for antigen, it might be possible to develop novel immunotherapeutic strategies for the treatment of seropositive rheumatoid arthritis. Studies described below review recent progress in understanding the components of the ternary complex and suggest possible areas of immunotherapeutic intervention. PMID- 1613730 TI - Excitement in synovium: the rapid evolution of understanding of rheumatoid arthritis and expectations for therapy. AB - Multiple events give rise to rheumatoid arthritis (RA) and many different elements create an overall pathological effect. It is highly unlikely that a single cause for RA will be identified. A greater appreciation of the multiple events that lead to the development of RA is opening up a number of promising points of intervention which may serve as potential alternatives to the broader based and often toxic drugs used in RA therapy today. PMID- 1613731 TI - Rheumatoid factors: historical perspective, origins and possible role in disease. AB - The recognition of antibodies by the immune system is more complex than previously believed. Rheumatoid factor (RF), a family of autoantibodies against gammaglobulin, has long been recognized as an important biologic marker for rheumatoid arthritis (RA). When RF contributes to the generation of the inflammatory aspects of RA, it probably does so by forming immune complexes that are themselves able to bring about the inflammatory response. Contrary to the widely accepted belief that RF somehow is triggered by recognition of self IgG, antibodies to viral Fc receptors may provide the initial stimulus for RF production in RA. PMID- 1613732 TI - Rheumatoid factors in the pathogenesis of rheumatoid arthritis. AB - Rheumatoid factors (RF) participate in the pathogenesis of rheumatoid arthritis by formation of immune complexes. IgM-RF form complement activating immune complexes with IgG-containing antigen-antibody complexes. IgG-RF form unique immune complexes without the presence of separate antigen molecules. The specificities of RF in rheumatoid arthritis have subtle differences from RF formed by B cell neoplasms. Immune deposits in rheumatoid articular cartilage have high potential for generating inflammation and contain RF. The immune deposits in articular cartilage need to be characterized further, and the mechanisms that initiate and perpetuate RF production in patients with rheumatoid arthritis should be elucidated. PMID- 1613733 TI - IgM rheumatoid factors in patients with rheumatoid arthritis derive from a diverse array of germline immunoglobulin genes and display little evidence of somatic variation. AB - Rheumatoid factors (RF) are present in the plasma of patients with rheumatoid arthritis (RA) although the site of synthesis of most of these antibodies is within the synovium. This report primary concerns RF of the IgM isotype. While a few of the RF derive from patients with systemic lupus erythematosus or from normal individuals, the remaining derive from the inflamed synovial tissue of patients with RA. Two RF are encoded by members of the VH1 gene family, 8 from the VH3 family and 2 from the VH4 family. Two polyreactive antibodies derive from the VH3 family and 2 come from the VH4 family. This distribution is not fundamentally different from the distributions seen in a large array of autoantibodies and antibodies to external antigens. Similarly, the light chains derive from most of the known kappa and lambda VL families. It is hard to escape the preliminary conclusion that gene segments from virtually any light chain variable region can contribute to RF or polyreactive antibody structures. Most IgM RF and polyreactive antibodies are direct copies of germline genes in one of their polypeptide chains or at most are 2 nucleotides away in one of their chains from a known germline gene. PMID- 1613734 TI - Binding characteristics of human hybridoma IgG and IgM rheumatoid factors: influence of IgG isotype and carbohydrate content. AB - The interaction of human monoclonal rheumatoid factors (RF) with the Fc portion of IgG is complex. We have investigated the influence of the nature of the antigen (Fc) on the binding of hybridoma-generated RF derived from patients with rheumatoid arthritis or systemic lupus erythematosus. For IgM RF, the interaction is strongly influenced by the primary structure of the Fc with little or no effect of the carbohydrate, which is positioned at amino acid 297 in the gamma-2 domain. In contrast, our preliminary data suggest that IgG RF binding is affected both by the primary structure and the nature of the carbohydrate of the Fc. These results suggest that the antigen selection events which lead to the induction and production of IgG RF are likely to be different from those that induce IgM RF production. PMID- 1613735 TI - Proteinases in rheumatoid arthritis. AB - The role of proteinases in the extracellular breakdown of the connective tissue matrix during disease processes is outlined. Focussing on the matrix metalloproteinases, we present an overview of the mechanisms regulating their activity. Methods of assessing their role in disease processes is exemplified by new data on stromelysin activity in remodelling joint tissues in both model systems and human disease. PMID- 1613736 TI - Epidemiologic studies of rheumatoid arthritis: future directions. AB - We (1) review the current status of epidemiologic studies of rheumatoid arthritis (RA); (2) consider the strengths and weaknesses of such studies and (3) offer suggestions regarding directions which future work might take. We will not examine any particular studies in great detail, but, instead, will focus on those broad aspects of epidemiologic work concerning RA which seem most important. In this process, it may be useful to draw comparisons with cancer epidemiology, since etiologic possibilities in cancer often resemble those seen in RA and similar methodologic issues are involved. PMID- 1613737 TI - Practice based evaluation of the longterm benefit of second line agents in rheumatoid arthritis. AB - A hypothetical practice based consortium to evaluate treatment of early rheumatoid arthritis (RA) is discussed. It would consist of a coordinating center and many practicing rheumatologists. Patients with RA within 3 to 12 months of disease onset who met strict entry criteria would be offered enrollment in their choice from a menu of protocols that includes standard and aggressive treatment options and would be followed for a long time. Standard efficacy assessments would be carried out at fairly long intervals, with emphasis on erosive changes in wrist, hands and feet x-rays. Analysis would be done across drug protocols within homogeneous subgroups of patients who have been stratified by comparable entry characteristics, using those who develop erosions during treatment with nonsteroidal antiinflammatory drugs only as the standard for comparison. This approach can be used to identify risk factors that predict subsequent erosive joint damage, and to select a few promising drugs, combinations and therapeutic strategies for subsequent definitive studies. PMID- 1613738 TI - Biological agents in rheumatoid arthritis. AB - New potential therapies using molecular biology technology are under development. The initial trials in rheumatoid arthritis (RA) with interferon gamma were disappointing. Cytokine inhibitors such as interleukin-1 receptor antagonist are beginning clinical trials. Growth factors have been used to treat isolated complications associated with RA. Monoclonal antibodies to target active cell lines or receptors are also under study with preliminary results available from several studies. This technology offers a hope lf more selective interventions for many systemic rheumatic diseases. PMID- 1613739 TI - Immunopathogenesis and treatment of rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology. Recent advances have suggested that T cells play a critical role in the immunopathogenesis of RA. A variety of clinical trials using a number of monoclonal antibodies have confirmed the hypothesis that CD4+ T cells play a central role in propagating the disease. Moreover, these trials have suggested rational approaches for the treatment of RA in the future. Despite a comprehensive view of the immunopathogenic processes causing the manifestations of the disease, the underlying cause of RA remains unknown. Critical aspects of RA that might be important in the early diagnosis and prognosis of the disease remain to be delineated. These include the precise role of the association with gene products of the major histocompatibility complex and possibly the role of other genetic elements. In addition, there is no information concerning potential etiologic agents. Delineation of these issues should provide additional insight into RA and potential approaches to treatment and prevention. PMID- 1613740 TI - From aspirin to biologics: therapeutic implications for rheumatoid arthritis. AB - As effective antiinflammatory agents have been added to our armamentarium, 2 major treatment strategies for the treatment of rheumatoid arthritis have developed. The traditional pyramid strategy is based on initial, conservative measures, followed by more aggressive therapy as the disease progresses. The step down bridge approach is an alternative, more aggressive strategy that favors earlier use of more potent agents. The longterm effects of disease modifying antirheumatic drugs (DMARD) and combination second line therapy on disease progression remain unclear. Advances in the development of more specific DMARD and in human recombinant proteins offer promising future therapies. PMID- 1613741 TI - Nonsteroidal antiinflammatory drugs: benefit/risk evaluation in rheumatic diseases. AB - Side effects of nonsteroidal antiinflammatory drug (NSAID) therapy are attributed to direct damage by the acidic compounds and to the secondary effects of prostaglandin inhibition. In general, gastrointestinal, skin and central nervous system effects predominate, followed by general adverse hepatic and renal events. Advanced age, female gender, history of gastrointestinal disorders and renal impairment increase the risk of NSAID induced side effects. Pharmacologic modifications that may help minimize side effects include lowered cyclooxygenase inhibitor activity, more stable plasma/tissue concentrations, decreased lipophilicity, avoidance of biliary excretion and renal excretion in inactive form. Prescribing NSAID according to their differing pharmacokinetic profiles may help maximize clinical efficacy and reduce side effects. PMID- 1613742 TI - 3D database searching in drug design. PMID- 1613743 TI - Orally active aldose reductase inhibitors: indazoleacetic, oxopyridazineacetic, and oxopyridopyridazineacetic acid derivatives. AB - Benzothiazole side chains featured in zopolrestat (1a) and its congeners were incorporated into oxophthalazineacetic acid replacements, including indazole, pyridazinone, and pyridopyridazinone with a pendant acetic acid moiety. Potent aldose reductase inhibition activity among resulting compounds is as widespread as it is in the earlier zopolrestat series, thus lending further support to our hypothesis that there is a binding site on the aldose reductase enzyme with strong affinity for benzothiazoles. Representative new compounds 1-[(5,7-difluoro 2-benzothiazolyl)-methyl]-1H-indazoleacetic acid (62), [6-[[5 (trifluoromethyl)benzothiazol-2-yl]methyl]-8-oxo- 6H-pyrido[2,3-d]-pyridazin-5 yl]acetic acid (70), 3,4-dihydro-4-oxo-5,6-dimethyl-3-[(5,7-difluorobenzothiazol 2-yl) methyl]-1-pyridazineacetic acid (79), and 3,4-dihydro-4-oxo-5,6-cyclohexano 3-[[5-(trifluoromethyl) benzothiazol-2-yl]-methyl]-1-pyridazineacetic acid (82) are potent aldose reductase inhibitors with IC50s of 30, 2.1, 5, and 52.2 nM, respectively. The best of these compounds, 79 and 82, also inhibit accumulation of sorbitol in rat sciatic nerve in a model of diabetic complications, when administered orally at 10 mg/kg. The inhibition values are 76 and 61%, respectively. In addition to benzothiazole, we have examined its surrogates effective in potentiating aldose reductase inhibition activity, including benzoxazole and aryl[1,2,4]oxadiazole. Structure-activity relationships emerging from this program are also discussed. PMID- 1613744 TI - Hydantoin bioisosteres. In vivo active spiro hydroxy acetic acid aldose reductase inhibitors. AB - The hypothesis that clinical side effects of the aldose reductase inhibitor (ARI) sorbinil were related to its hydantoin ring led to a bioisosteric analysis and replacement of the hydantoin by a spiro hydroxy acetic acid moiety as in 40. These hydroxy acids, compared to hydantoins, showed a similar potency increase on chroman 2-methyl substitution, a similar orthogonal relationship of acidic to aromatic moieties, and similar ARI enantioselectivity. In this series the six membered spiro hydroxy acetic acid anion array is a bioisostere for a spiro hydantoin anion and leads to ARIs with excellent in vivo activity. In vitro and in vivo activity was improved over 40 by chroman cis 2-methylation as in 4 and by aromatic 6,7-halogen substitution. Compounds with the best acute in vivo activity in rats were compared for chronic in vivo activity. The highest tissue levels and best chronic in vivo activities were found in the racemic 6,7-dichloro and 6 fluoro-7-chloro analogues 18 and 23. ARI activity was enantioselective for 58 and 60, the 2R,4R-enantiomers of 18 and 23. 7-Chloro-6-fluoro-cis-4-hydroxy-2(R) methyl-chroman-4-acetic acid (60) was selected for phase 1 clinical trials and did not exhibit sorbinil-like hypersensitivity side effects. PMID- 1613745 TI - Synthesis of carbon-11 labeled iodinated cocaine derivatives and their distribution in baboon brain measured using positron emission tomography. AB - Three iodine-substituted derivatives of cocaine, methyl esters of 3-[(2'-, 3'-, and 4'-iodobenzoyl)oxy]-8-methyl-[1R-(exo,exo)]-8- azabicyclo[3.2.1]octane-2 carboxylic acid (2a-c), were synthesized and subjected to N-demethylation to give the corresponding noriodococaines 3-[(2'-,3'-, and 4'-iodobenzoyl)oxy]-[1R (exo,exo)]-8- azabicyclo[3.2.1]-octane-2-carboxylic acid (3a-c). These were remethylated with [11C]CH3I to give the [N-11C-methyl]iodococaines 4a-c which were examined in baboon brain in vivo using positron emission tomography (PET). Compared to [N-11C]cocaine itself the regional distributions were changed from a highly specific localization in the corpus striatum to more diffuse patterns which included the cerebellum and cortex. Peak brain uptakes and clearance kinetics were also changed. [N-11C]-o-Iodococaine (4a) had a peak uptake in the striatum at 4-5 min after injection of only 17% that of cocaine in the same animal. The peak uptake of [N-11C]-p-iodococaine (4c) was 60% of that of [N 11C]cocaine and a clearance half-time of approximately 55 min, twice that of [N 11C]cocaine. [N-11C]-m-Iodococaine (4b) displayed half the uptake of [N 11C]cocaine, buts its clearance was similar to that of the parent molecule. The fractions of unmetabolized tracer in blood plasma at 1-30 min were higher for 4a c than for [N-11C]cocaine. Plasma protein binding experiments showed 10%, 0.3%, 1.6%, and 6% as the free fraction for cocaine and o-, m-, and p-iodococaines respectively, consistent with the low brain uptake observed for the ortho isomer, and implicated alpha 1-acid glycoprotein as responsible for the low free fraction of o-iodococaine. The potencies of 2a-c to displace tritiated cocaine from striatal membranes were p-iodo approximately cocaine greater than m-iodo approximately o-iodo. PMID- 1613746 TI - Synthesis and muscarinic receptor activity of ester derivatives of 2-substituted 2-azabicyclo[2.2.1]heptan-5-ol and -6-ol. AB - Radioligand binding affinities of four new muscarinic antagonists and six potential muscarinic agonists which possess the 2-alkyl-2 azabicyclo[2.2.1]heptane ring system have been determined in rat heart, rat brain, and m1- or m3-transfected CHO cell membrane preparations to examine the selectivity for subtypes of muscarinic receptor. The efficacies of the potential muscarinic agonists were determined by the ratio of binding affinities against [3H]QNB and [3H]Oxo-M. Four muscarinic antagonists which have the 2,2 diphenylpropionate side chain at either the C5 (5-endo or 5-exo) or the C6 (6 endo or 6-exo) positions did not discriminate between the subtypes of muscarinic receptors. The 2,2-diphenylpropionate 5-endo substituted compound was the most potent, showing affinities between 4.23 x 10(-10) and 1.18 x 10(-9) M in rat heart, rat brain, and m1- or m3-transfected CHO cell membrane preparations. The rank order of ester potency was 5-endo greater than 5-exo greater than 6-endo greater than 6-exo. A molecular modeling study based on the pharmacophore developed for azaprophen was used to account for the relative potency of these antagonists. Six potential muscarinic agonists which have acetoxy groups in the C5 or C6 position with an N-methyl or N-benzyl substituent did not discriminate subtypes of muscarinic receptors and had affinities between 6.63 x 10(-6) and 4.76 x 10(-5) M in rat heart, rat brain, and m1- or m3-transfected CHO cell membrane preparations. exo-2-Methyl-5-acetoxy-2-azabicyclo[2.2.1]heptane was the most efficacious partial agonist. PMID- 1613747 TI - Synthesis and aromatase inhibition of 3-cycloalkyl-substituted 3-(4 aminophenyl)piperidine-2,6-diones. AB - The synthesis of 3-cycloalkyl-substituted 3-(4-aminophenyl)piperidine-2,6-diones is described [cyclopentyl (1), cyclohexyl (2)]. The enantiomers of 2 were separated either by using HPLC on optically active sorbent or by crystallization of the brucine salt of the phthalamic acid of 2. The absolute configuration of the (+)- and (-)-enantiomers of 2 were assigned as S and R, respectively, by comparing the CD spectra to those of the enantiomers of aminoglutethimide (AG, 3 (4-aminophenyl)-3-ethylpiperidine-2,6-dione). The compounds were tested in vitro for inhibition of human placental aromatase, the cytochrome P450-dependent enzyme which is responsible for the conversion of androgens to estrogens. Compounds 1 and 2 inhibited aromatase by 50% at 1.2 and 0.3 microM, respectively (IC50 AG = 37 microM). According to the findings with AG, the (+)-enantiomer of 2 was responsible for the inhibitory activity, being a 240-fold more potent aromatase inhibitor in vitro than racemic AG. On the other hand, (+)-2 displayed a strongly reduced inhibition of desmolase (cholesterol side-chain cleavage enzyme) compared to AG (relative activity = 0.3). Thus (+)-2 is of interest as a potential drug for the treatment of estrogen-dependent diseases, e.g. mammary tumors. PMID- 1613748 TI - Iodoaminopotentidine and related compounds: a new class of ligands with high affinity and selectivity for the histamine H2 receptor. AB - The synthesis and biological evaluation of a new class of histamine H2 antagonists with N-cyano-N'-[omega-[3-(1-piperidinylmethyl)phenoxy] alkyl]guanidine partial structure are described as part of an extensive research program to find model compounds for the development of new radioligands with high H2 affinity and specific activity. High receptor affinity is achieved by an additional (substituted) aromatic ring, which is connected with the third guanidine N by a carbon chain spacer and an amine, carboxamide, ester, or sulfonamide link ("polar group"). In functional studies for H2 antagonistic activity and other pharmacological actions [e.g. H1 antihistaminic, antimuscarinic, antiadrenergic (alpha 1, beta 1), 5-HT2 blocking activity] in the isolated guinea pig atrium and ileum and rat aorta and tail artery, the compounds proved to be highly potent and selective histamine H2 receptor antagonists. The H2 antagonistic activity is mainly depending on the length of both the N'-alkyl chain (chain A) and the N"-spacer (chain B). Compounds with a C3 chain A and a C2 chain B are most potent in the preferred group of substances, i.e., the carboxamide series. A wide variety of substituents at the aromatic ring is tolerated, among them iodine, amino, and azido groups. These compounds are up to 32 times more potent than cimetidine in the isolated guinea pig right atrium. The replacement of the carboxamide by an ester group (44c) is well tolerated, while replacement of the cyanoguanidine by an urea group results in nearly 100-fold decrease in activity (46c,e). The iodinated benzamides are among the most potent H2 antagonists known so far. The [125I]-labeled form of 31f ([125I]iodoaminopotentidine, [125I]-N-[2-(4-amino-3-iodobenzamido) ethyl]-N' cyano-N"-[3-[3-(1-piperidinylmethyl) phenoxy]propyl]guanidine) and its photolabile analogue 31h ([125I]iodoazidopotentidine, [125I]-N-[2-(4-azido-3- iodobenzamido)ethyl]-N'-cyano-N"-[3-[3-(1-piperidinyl-methyl)pheno xy] propyl]guanidine) proved to be useful probes for reversible and irreversible labeling of the histamine H2 receptor. Radioligand binding studies in guinea pig cerebral membranes revealed considerably higher H2 receptor affinity for 31f (pKi = 9.15), 31h (pKi = 8.58), and some analogues than functional experiments (guinea pig atrium), presumably reflecting an easier access to the H2 receptors in membranes. PMID- 1613749 TI - Active conformation of a tumor promoter, teleocidin. A molecular dynamics study. AB - Telecidins are potent tumor promoters, having a nine-membered lactam structure. Teleocidins and their small-molecular-sized active congeners (indolactams) are known to exist in an equilibrium between at least two conformational states, the twist and the sofa form. Molecular dynamics (MD) calculations were performed on four indolactams, in order to examine the relationships between preferred ring conformations and the biological activities. It was shown that the tumor promoting activities are closely related with the existence ratio of the sofa form among 10 possible conformations. This implies that the sofa form is the active ring conformation, which is compatible with the previous result obtained independently from the superposition of teleocidin and phorbol ester. The predicted ratios of conformers for each indolactam were in good agreement with those observed by NMR spectral analysis. The high-temperature MD method proved to be very useful for predicting the preferred structures of these cyclic compounds, in which the overall stabilities are strongly influenced by the conformations of substituent groups on the ring. PMID- 1613750 TI - Nucleosides and nucleotides. 107. 2-(cycloalkylalkynyl)adenosines: adenosine A2 receptor agonists with potent antihypertensive effects. AB - Adenosine receptor-binding profiles in rat brain tissues and antihypertensive effects in spontaneously hypertensive rats (SHR) of a series of 2 (cycloalkylalkynyl)adenosines (2-CAAs) and their congeners are described. The structure-activity relationship of this series of compounds is discussed, focusing on the length of the alkynyl side chain and bulkiness of the terminal cycloalkyl substituents in terms of binding activity and cardiovascular effects. All the 2-CAAs had a preferential affinity for A2 receptors. Of these derivatives, 2-(3-cyclopentyl-1-propyn-1-yl)adenosine (10b) exhibited the most selective affinity for A2 receptors (Ki ratio: A1/A2 = 70) on the basis of receptor binding. In the C-2 binding region of adenosine, compounds often have potent and/or selective A2 activity from introduction of an acetylenic group at the C-2 position followed by one methylene residue further followed by a hydrophobic substituent such as a cycloalkyl ring at the terminal position of the alkynyl side chain. Intravenous injection of 10b up to 100 micrograms/kg had a potent hypotensive effect without a marked decrease in heart rate in anesthetized SHR. Compounds 10j-s, with a hydroxyl group in the C-3" position of the alkynyl side chain, had a potent affinity for both A1 and A2 receptors, but they were not highly selective for A2 receptors. These compounds caused a marked bradycardia upon intravenous administration in anesthetized SHR. Oral administration of 10b (0.1-1 mg/kg) had a potent and long-lasting antihypertensive effect in conscious SHR. PMID- 1613751 TI - Novel functional M1 selective muscarinic agonists. Synthesis and structure activity relationships of 3-(1,2,5-thiadiazolyl)-1,2,5,6-tetrahydro-1 methylpyridines . AB - A series of novel 3-(3-substituted-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro- 1 methylpyridines (substituted-TZTP; 5a-l, 7a-h, 8, 9c-n, 11, 13j) were synthesized and tested for central muscarinic cholinergic receptor affinity by using [3H] oxotremorine-M (Oxo-M) and [3H]-pirenzepine (Pz) as ligands. The potency and efficacy of the compounds for the pharmacological defined M1 and M2 muscarinic receptors were determined on isolated electrically stimulated rabbit vas deferens and on spontaneously beating isolated guinea pig atria, respectively. Selected compounds were also tested for M3 activity in the isolated guinea pig ileum. The C1-8 alkoxy-TZTP 5a-l analogues all displaced [3H]-Oxo-M and [3H]-Pz with low nanomolar affinity. Depicting chain length against Oxo-M binding and against Pz binding the unbranched C1-8 alkoxy-TZTP (5a-h) derivatives produced U-shaped curves with butoxy- (5d) and (pentyloxy)-TZTP (5e) as the optimum chain length, respectively. This U-shaped curve was also seen in the ability of the compounds 5a-h to inhibit the twitch height in the vas deferens preparation. The (pentyloxy)- (5e) and the (hexyloxy)-TZTP (5f) analogues produced an over 90% inhibition of the twitch height with IC50 values in the low picomolar range. In both the atria and in the ileum preparations 5f had low efficacy and potency. With the (alkylthio)-TZTP (7a-h) analogues the structure-activity relationship was similar to the one observed with the alkoxy (5a-h) analogues, but generally 7a-h had higher receptor affinity and was more potent than the corresponding 5a h. However, the C3-8 alkyl-TZTP (9c,e,g,h) analogues had 10-100 times lower affinity for the central muscarinic receptors than the corresponding alkoxy and alkylthio derivatives, and their efficacy in the vas deferens preparation was too low to obtain IC50 values. The unsubstituted TZTP (11) compound was a potent but nonselective muscarinic agonist. The two 3-(3-butoxy/(hexyloxy)-1,2,5-oxadiazol-4 yl)-1,2,5,6-tetrahy dro-1- methylpyridines (butoxy/hexyloxy)-OZTP; 19a/b) were also synthesized and tested. Both 19a and 19b had much lower affinity for the central muscarinic receptors than 5d and 5f, and the efficacy of 19a,b was too low to give IC50 values in the vas deferens preparation. Therefore, the C5-6 (alkyloxy)/(alkylthio)-TZTP's represent a unique series of potent functional M1 selective muscarinic agonists. PMID- 1613752 TI - Nucleic acid related compounds. 74. Synthesis and biological activity of 2'(and 3')-deoxy-2'(and 3')-methylenenucleoside analogues that function as mechanism based inhibitors of S-adenosyl-L-homocysteine hydrolase and/or ribonucleotide reductase. AB - Treatment of 2-amino-6-chloro-9-(beta-D-ribofuranosyl)purine (21) with TBDMS chloride/imidazole/DMF gave a separable mixture of 5'-O, 2',5'-bis-O (22), 3',5' bis-O (23), and 2',3',5'-tris-O-TBDMS derivatives. Oxidation of 22 and 23 with CrO3/pyridine/Ac2O, treatment of the respective ketonucleosides with methylenetriphenylphosphorane, and deprotection gave 2-amino-6-chloro-9-[3(and 2) deoxy-3(and 2)-methylene- beta-D-erythro-pentofuranosyl]purines (28 and 37) that were converted into other 2-amino-6-substituted-purine analogues. Tubercidin was converted into 2'-deoxy-2'-methylenetubercidin (49) by an analogous route. Inactivation of S-adenosyl-L-homocysteine hydrolase by 2'- and 3' methyleneadenosine analogues was investigated. Mechanism-based inhibition of S adenosyl-L-homocysteine hydrolase and anticancer and antiviral activities of 2'(and 3')-deoxy-2'(and 3')-methylenenucleoside analogues are discussed. PMID- 1613753 TI - Synthesis and evaluation of analogues of (Z)-1-(4-methoxyphenyl)-2-(3,4,5 trimethoxyphenyl)ethene as potential cytotoxic and antimitotic agents. AB - A series of stilbenes has been prepared and tested for cytotoxicity in the five human cancer cell lines A-549 non-small cell lung, MCF-7 breast, HT-29 colon, SKMEL-5 melanoma, and MLM melanoma. The cis stilbenes 6a-f proved to be cytotoxic in all five cell lines, with potencies comparable to that of combretastatin A-4. These cytotoxic compounds were all potent inhibitors of tubulin polymerization. The corresponding trans stilbenes 7b-f were inactive as tubulin polymerization inhibitors and were significantly less cytotoxic in the five cancer cell lines. In the dihydro series, 8b, 8c, and 8f were inactive as tubulin polymerization inhibitors, while 8a, 8d, and 8e were less active than the corresponding cis compounds 6a, 6d, and 6e. The lack of tubulin polymerization inhibitory activity and cytotoxicity displayed by the phenanthrene 23b, which was synthesized as a conformationally rigid analogue of the lead compound 1, indicates that the activity of the stilbenes is not due to a totally planar conformation. Similarly, inactivity of the conformationally restricted analogue 26 suggests that the biologically active conformation of 1a resembles that of the cis alkene 1. Additional inactive compounds prepared include the benzylisoquinoline series 28 32 as well as the protoberberines 38 and 39. Shortening the two-carbon bridge of 1a to a one-carbon bridge in the diphenylmethane 20 resulted in a decrease in cytotoxicity and tubulin polymerization inhibitory activity. Although the corresponding benzophenone 18 was as active as 1a as a tubulin polymerization inhibitor, it was less cytotoxic than 1a, and the benzhydrol 19 was essentially inactive. With the exception of the amide 15c, which displayed low antitubulin activity, all of the phenylcinnamic acid derivatives 14a-c and 15a-f were inactive in the tubulin polymerization inhibition assay. The acid 14b and the ester 15a were cytotoxic in several of the cancer cell cultures in spite of their inactivity as tubulin polymerization inhibitors. PMID- 1613754 TI - Structural studies on bio-active compounds. 20. Molecular modeling and crystallographic studies on methylbenzoprim, a potent inhibitor of dihydrofolate reductase. AB - Methylbenzoprim (MBP) is a potent inhibitor of dihydrofolate reductase, which is more selective for mammalian than bacterial enzymes. Crystal-structure studies on the free base of MBP, with two independent molecules, and the ethanesulfonate salt, have demonstrated three significantly different conformations for MBP. With the MOPAC optimized MBP cation as starting point, the COSMIC energy was monitored as torsion angles were changed in 5 degrees increments. The barrier to rotation about C(5)-C(11) can create two slowly interconverting rotamers, in agreement with NMR studies. Two conformations of the cation that fit the human DHFR structure from the Brookhaven Protein Data Bank have been found. They differ chiefly by a half-turn about C(5)-C(11), positioning the nitro group on opposite sides but allowing the central and benzylic rings to find hydrophobic surroundings. The central ring is close enough to the predicted position of the cofactor NADPH to make competition likely. Kinetic studies with rat liver DHFR show that MBP is an inhibitor that competes with NADPH as well as dihydrofolate. PMID- 1613755 TI - Quinazoline antifolate thymidylate synthase inhibitors: difluoro-substituted benzene ring analogues. AB - The synthesis of a series of new C2-methyl-N10-alkylquinazoline-based thymidylate synthase (TS) inhibitors containing difluroinated p-aminobenzoate rings is described. Derivatives of the N10-propargyl and N10-methylquinazoline antifolates were prepared with 2',3'-, 2',5'-, and 2',6'-difluoro substitution. The synthesis of the 2',5'-difluoro analogues involved oxidation of the difluoronitrotoluene to 2,5-difluoro-4-nitrobenzoic acid followed by glutamation, reduction, and alkylation (propargyl bromide or MeI) to the diethyl N-(4-(alkylamino)-2,5 difluorobenzoyl)-L-glutamates. For the synthesis of the 2',3'- and 2',6'-difluoro compounds a new route was devised starting from methyl 4-((tert butoxycarbonyl)amino)-2,6-difluorobenzoate and its 2,3-substituted counterpart. Treatment with NaH and then an alkyl halide introduced the N10-substituent. The methyl ester was hydrolyzed and the resulting acid was condensed with diethyl L glutamate. The secondary amine was liberated using CF3CO2H and coupled with 6 (bromo-methyl)-3,4-dihydro-2-methyl-4-oxoquinazoline to yield the antifolate diesters. Final deprotection with mild alkali completed the synthesis in each case. The target compounds were tested as inhibitors of partially purified L1210 TS and also examined for their inhibition of the growth of L1210 cells in culture. Compared to their nonfluorinated parent compounds all the difluoro analogues were poorer inhibitors of TS. The greatest loss of enzyme activity was seen in the N10-propargyl analogues which contained one of the fluorine atoms ortho to the amine substituent. This loss was less apparent in the N10-methyl derivatives. Despite this lower inhibition of TS the majority of new compounds have equivalent cytotoxicity to their nonfluorinated predecessors. PMID- 1613756 TI - Structure-activity studies of potassium channel opening in pinacidil-type cyanoguanidines, nitroethenediamines, thioureas, and ureas. AB - Potassium channel opening activity for pinacidil-type cyanoguanidines, nitroethenediamines, thioureas, and ureas, has been assessed through simultaneous measurement of spontaneous contractile activity and stimulation of 86Rb+ efflux from rat portal veins loaded with 86Rb+. The good correlation between these two effects suggests that the vasodilator activity of the compounds is directly attributable to an increased opening of potassium channels. The resulting quantitative in vitro data has been used to analyze the structure-activity relationships for potassium channel opening, allowing the biological activity to be rationalized in terms of a pharmacophore involving a hydrogen-bond-acceptor element, a hydrogen-bond-donor element, and a lipophilic binding group. A model for the binding of pinacidil-related compounds to their potassium channel receptor has been developed, and compounds designed to test this model have been synthesized and tested. Prototropic equilibria are implicated as playing a fundamental role in determining the hydrogen-bonding ability of the compounds, and conformational changes in the receptor are invoked to explain disparities in the chiral recognition of lipophilic groups in different compounds. PMID- 1613757 TI - 7-Oxabicycloheptylprostanoic acids: potent, time-dependent cyclooxygenase inhibitors that induce a conformational change in the prostaglandin endoperoxide synthase protein. PMID- 1613758 TI - (E)-1,3-dialkyl-7-methyl-8-(3,4,5-trimethoxystyryl)xanthines: potent and selective adenosine A2 antagonists. PMID- 1613759 TI - Estimates of the frequency of chromosome abnormalities detectable in unselected newborns using moderate levels of banding. AB - Data on structural chromosome abnormalities identified during prenatal diagnosis were used to estimate the number of such abnormalities that would be detectable in an unselected series of newborns using moderate levels of banding (400 to 500 bands). These estimates were compared with the rates detected in nonbanded surveys of newborns. Between 1976 and 1990 prenatal diagnosis using banding techniques was carried out in our laboratory on 14,677 women aged 35 and over. Among these, we detected 112 structural rearrangements, 32 unbalanced and 80 balanced. These figures were adjusted by two methods to give an estimate of the frequency of structural abnormalities in the newborn. Our data suggest that the use of moderate levels of banding increases the frequency of unbalanced structural abnormalities from 0.052 to 0.061% and of balanced structural abnormalities from 0.212 to 0.522%. Thus, the total number of chromosome abnormalities detectable in the newborn is increased from 0.60% in unbanded preparations to 0.92% in banded preparations. PMID- 1613760 TI - Cyclophosphamide increases the frequency of sister chromatid exchange in direct preparations of human chorionic villi in the absence of supplementary enzymatic activation systems. AB - A study was performed to evaluate the effect on the frequency of sister chromatid exchange in first trimester chorionic villi of two chemical compounds, mitomycin C and cyclophosphamide. Mitomycin C is generally known to induce an increase in sister chromatid exchange both in vivo and in vitro standard conditions. Cyclophosphamide is a compound requiring additional enzymatic enrichment of the culture medium to express its mutagenic activity under in vitro conditions. We exposed chorionic villi samples to these chemicals without the use of conventional cell cultures and without adding enzymatic extracts to the medium. The results indicate a statistically significant increase in the frequency of sister chromatid exchange after exposure to both compounds and also at lower dosages. PMID- 1613761 TI - The clinicopathological features of three babies with osteogenesis imperfecta resulting from the substitution of glycine by valine in the pro alpha 1 (I) chain of type I procollagen. AB - The features of three babies with perinatal lethal osteogenesis imperfecta (OI II) resulting from substitutions of glycine by valine in the triple helical domain of the alpha 1(I) chain of type I collagen were studied. The babies were heterozygous for this substitution at residue 1006 in case 1 (OI35), 973 in case 2 (OI59), and 256 in case 3 (OI7B). OI35 had the most severe clinical form, OI IIC, with premature rupture of membranes, severe antepartum haemorrhage, stillbirth, severe short limbed dwarfism, and extreme osteoporosis. OI59 was a better formed baby but was also born prematurely as a result of premature rupture of membranes and severe antepartum haemorrhage. She had the radiographic features of OI IIA. OI7B was born at term and also had the radiographic features of OI IIA. Pathological examination of the skeletons of OI35 and OI59 showed grossly deficient intramembranous and endochondral ossification. Trabecular bone was sparse in the long bones and vertebrae. The trabeculae contained a cartilage core and an overlying layer of woven bone or osteoid. The diaphyses lacked cortical bone. The periosteal fibroblasts of OI35 contained grossly distended rough endoplasmic reticulum consistent with the 53% reduction in collagen secretion by cultured dermal fibroblasts. The aorta, skin, and lungs were hypoplastic in OI35 and OI59. The findings in this study show that glycine substitutions by valine in Gly-X-Y triplets, from glycine 256 to glycine 1006, of the triple helical domain of alpha 1(I) chains produce the OI II phenotype. The phenotype was most severe in the baby with the most carboxy-terminal substitution. PMID- 1613763 TI - Recurrence of neural tube defect in a group of at risk women: a 10 year study of Pregnavite Forte F. PMID- 1613762 TI - Screening for mutations in the muscle promoter region and for exonic deletions in a series of 115 DMD and BMD patients. AB - Mutations in the muscle promoter region and exonic deletions were screened in a series of 115 unrelated DMD and BMD patients from north-east Italy. No gross mutations of the promoter region were found. In three cases in which dystrophin of normal size was expressed at low levels, the analysis of DNA sequences of the promoter region failed to detect abnormalities. The majority of deletions in coding sequences, detected by cDNA probes, occur in the deletion hot spot identified by the probe P20. Intrafamilial variability in the severity of the disease is reported and discussed. PMID- 1613764 TI - Unusual T cell clones in a patient with Nijmegen breakage syndrome. AB - The rare autosomal recessive Nijmegen breakage syndrome is characterised by severe immunodeficiency, microcephaly associated with mental retardation, and typical chromosomal rearrangements in peripheral T lymphocytes. This syndrome, though similar to ataxia telangiectasia, does not exhibit the neurological and cutaneous signs of this disorder. We report here the first patient with Nijmegen breakage syndrome ascertained in France. Chromosome analysis detected, in addition to the specific aberrations, two clonal T cell proliferations which do not involve the usual bands 14q11.2 and 14q32.1. PMID- 1613765 TI - Meckel syndrome and neural tube defects in Kuwait. PMID- 1613766 TI - Sociocultural problems in genetic counselling. PMID- 1613767 TI - Maxillonasal dysplasia (Binder's syndrome) and chondrodysplasia punctata. PMID- 1613768 TI - Marfan syndrome: a mystery solved. PMID- 1613769 TI - A linkage map of 10 loci flanking the Marfan syndrome locus on 15q: results of an International Consortium study. AB - Members of an International Consortium for Linkage Analysis of the Marfan Syndrome (MFS1) have pooled data for joint analysis in an attempt to determine the precise location of the MFS1 gene and the order of 10 DNA markers on 15q. Five laboratories performed a total of 2111 genotypes in 22 families consisting of 225 affected and 248 normal subjects. For each marker a mean of 98 meioses was informative. D15S48 and D15S1 were identified as the closest linked markers with 99% upper confidence intervals of 12% and 13% respectively. We have used the CRI MAP program to construct the most likely order as: D15S24-D15S25-D15S1-MFS1 D15S48-D15S49+ ++-(D15S45/S51)-(D15S29/S38). Placement of D15S2 in relation to D15S1-D15S48- cannot be determined with certainty. The genetic map of these markers extends 53.6 cM in males and 65.0 cM in females with a sex averaged map of 60.7 cM. The sex difference was statistically significant (p = 0.005). Linkage heterogeneity between 22 MFS1 families was documented (p = 0.009) necessitating the exclusion of one family from the analysis. However, comparison of the remaining 21 families for two point and multipoint lod scores showed no evidence for linkage heterogeneity of the MFS1 locus. PMID- 1613770 TI - Marfan syndrome in a large family: response of family members to a screening programme. AB - Reaction to medical, social, and genetic implications of Marfan syndrome was evaluated by means of two questionnaires, the first after various tests before discussion of the diagnosis, the second after full discussion of the patient's diagnosis. Thirty-seven members of a family known to be at risk for Marfan syndrome attended for both questionnaires. All patients claimed to be satisfied with the way they were informed of the results of screening; 41% of patients were more worried about their health and 48% were more worried about the future after diagnosis. Apart from 50% of the smokers reducing or stopping their intake of cigarettes there were only very minor changes in lifestyle over the first month despite the increased level of expressed anxiety. If a definitive screening test was available, 96% of patients claimed they would have chosen it, 45% felt it would have an influence on their future plans, and 78% would choose to use a method of prenatal diagnosis for Marfan syndrome if it were available. PMID- 1613771 TI - Sensorineural deafness inherited as a tissue specific mitochondrial disorder. AB - We present here a large Israeli-Arab kindred with hereditary deafness. In this family 55 deaf subjects (29M, 26F), who are otherwise healthy, have been identified and traced back five generations to one common female ancestor. The deafness is progressive in nature, usually presenting in infancy and childhood. Audiometry on six deaf and seven unaffected subjects was consistent with severe to profound sensorineural hearing loss. Based on formal family segregation analysis, the inheritance of deafness in this family closely fits the expectation of a two locus model owing to the simultaneous mutation of a mitochondrial gene and an autosomal recessive gene. Thus, this disorder appears to have the unusual features of being an inherited tissue specific mitochondrial disease and apparently requiring the homozygous presence of a nuclear gene for clinical expression. Most importantly, this disorder presents a unique opportunity to investigate the molecular basis of hereditary non-syndromic deafness and normal hearing. PMID- 1613772 TI - Fetal hydrops. AB - Seventy-two fetuses or neonates with non-immune hydrops were examined between 1983 and 1988. The commonest association was chromosome abnormality; 11 fetuses had a 45,X karyotype and 11 autosomal trisomy. Chromosome abnormality was suspected in a further 20 on necropsy findings but chromosome culture was not possible or unsuccessful. In 11 cases there was histological evidence of infection; seven babies had major structural anomalies and six affected fetuses were twins. In six (8%) the cause of hydrops was not determined compared with eight (16%) of cases examined between 1976 and 1982. Hydrops was diagnosed more frequently while the fetus was alive, before 20 weeks' gestation, and associated with chromosome anomaly than found previously. PMID- 1613773 TI - Chromosome in situ suppression hybridisation in human male meiosis. AB - Chromosome in situ suppression hybridisation with biotinylated whole chromosome libraries permits the unequivocable identification of specific human somatic chromosomes in numerous situations. We have now used this so called 'chromosome painting' technique in meiotically dividing cells, isolated from human testicular biopsy. It is shown that the method allows identification of target homologues, bivalents, and sister chromatids throughout the relevant stages of meiosis. Thus, a more accurate study of meiosis per se is now available to increase our understanding of such processes as first meiotic synapsis of homologues and chiasma formation/meiotic crossing over, which are still outstanding biological enigmas. The new technology also makes it possible, for the first time, (1) to obtain direct numerical data in first meiotic non-disjunction for individual chromosomes, and (2) to quantify segregation in male carriers of structural rearrangements. We exemplify the use of the chromosome painting technique for a first meiotic segregation analysis of an insertional translocation carrier. PMID- 1613774 TI - Rapid identification of Legionella species from a single colony by gas-liquid chromatography with trimethylsulphonium hydroxide for transesterification. AB - Transesterification of bacterial fatty acids to methyl esters with trimethylsulphonium hydroxide (TMSH) was compared with a conventional method for the identification of Legionella species by capillary gas chromatography. There was an extensive coincidence in the gas chromatographic profiles of bacterial fatty acid methyl esters (FAMEs) obtained by the two methods. However, the TMSH procedure needs less initial material and is much more simple and rapid. The chromatographic pattern of FAMEs obtained from a single colony is sufficient for the identification of the genus Legionella, and L. pneumophila can be clearly distinguished from other Legionella species. PMID- 1613775 TI - Dissemination and proliferation of Salmonella typhimurium in genetically resistant and susceptible mice. AB - Genetically resistant A/J and CBA mice were inoculated intraperitoneally with either 10(3) or 10(4) organisms of a virulent strain of Salmonella typhimurium; susceptible C57BL/6J and BALB/c mice were inoculated with either 10(2) or 10(3) organisms. Except with the smaller dose in resistant mice, fatal infection ensued. Bacteraemia occurred within 1 h after inoculation, except that it was not detectable during the first 6 h in the susceptible mice inoculated with 10(2) organisms. From day 2, the circulating bacterial population continued to increase in all infected mice, except that it remained under control in the resistant mice inoculated with the lower dose (10(3) organisms). The pathogen proliferated logarithmically in the liver from day 2, and a bacterial count of c. 10(8) cfu/g of tissue was reached when the animals died at 5-7 days; again, the resistant mice inoculated with 10(3) organisms were an exception in which the hepatic bacterial population was kept under control and the mice survived. PMID- 1613776 TI - Application of biochemical fingerprinting to the investigation of clonal groups of Salmonella of serotype Havana. AB - A computerised typing method based on biochemical fingerprinting was used to investigate biochemical phenotypes (BPTs) among 70 strains of Salmonella of serotype Havana isolated from human cases of gastroenteritis in Iran and other parts of the world. A total of 16 BPTs comprising five common and 11 single phenotypes was identified. The most frequently found BPT contained 24 isolates from Iran and nine from other countries. Three common BPTs with two, seven and 15 isolates were found among Iranian strains only and one common BPT with two isolates was found among non-Iranian strains only. Antibiotic-resistance patterns and virulence properties of strains from these common BPTs suggested that they might be unique clones. Forty-two Iranian isolates shared multi-resistance to between three and seven antibiotics. In contrast, none of the isolates from other countries was resistant to antibiotics. Furthermore, 43 Iranian isolates showed mannose-resistant adhesion to HeLa cells and 24 of them possessed an aerobactin mediated iron-uptake system, whereas none of the isolates from other countries possessed any of these virulence properties. These findings suggest that four unique clones of Salmonella Havana with different BPTs and virulence properties are common in Iran; two particular clones were responsible for a majority of Havana infections there. However, the most prevalent BPT found among Iranian strains was also common in strains from other countries. It is concluded that biochemical fingerprinting, as used in this study, is a reliable method for identifying clonal groups of Havana strains. The method is reproducible, easy to perform and can be used alone, or in combination with other typing methods, in epidemiological studies of serotype Havana. PMID- 1613777 TI - In-vitro and in-vivo characteristics of TnphoA mutant strains of Salmonella serotype Gallinarum not invasive for tissue culture cells. AB - Insertion mutants of a strain of Salmonella serotype Gallinarum, the cause of fowl typhoid, were produced with transposon TnphoA. Eight mutants were identified as being less invasive in cell culture than the parent strain. Neither the parent strain nor the mutants showed mannose-sensitive haemagglutination of various red blood cell species. Although two mutants gave mannose-resistant (MR) haemagglutination of red cells of different animal species these MR activities could not be correlated with other characteristics in vitro or in vivo. The mutant strains were divisible into three classes by their patterns of invasiveness and adhesiveness in vitro and by changes in membrane proteins. Strains of classes 1 and 2 had single transposon insertions, detected by Southern hybridisation, of 8.9 and 2.4 kb EcoRV-digested chromosomal-fragments, respectively, and were slightly less invasive than the parent strain. They were no less virulent for chickens by the oral route than a mutant strain shown to be as invasive in vitro as the parent strain. The class-2 mutant was also less adhesive than the other strains. The single mutant strain of class 3 which contained insertions in several chromosomal fragments, was non-invasive in Vero cells (less than log10 1.0 cfu/ml recovered compared with log10 2.88 for the parent strain) and showed reduced virulence by both oral and intramuscular routes. The mutant strains of all classes were taken up equally rapidly from the blood by the spleen. Intramuscular immunisation of chickens with the class-3 mutant strain gave complete protection against oral challenge 3 weeks later with 1000 oral LD50 doses of the virulent parent strain. PMID- 1613778 TI - Comparison of rapid methods for detection of heat-labile (LT) and heat-stable (ST) enterotoxin in Escherichia coli. AB - Oxoid VET-RPLA, ST-EIA and Pharmacia Phadebact ETEC-LT enterotoxin tests were compared to find a simple but reliable method for detecting enterotoxigenic Escherichia coli (ETEC) in Hungary. In the Oxoid tests, all six reference LT- or ST-producing strains, except one ST-producer, gave positive results. Of 11 reference porcine enterotoxigenic strains, all four LT-producers gave positive reactions for LT but three of 10 ST-producers gave negative reactions for ST. Thirteen of 50 strains from culture collections of H. Steinruck (Germany) were LT+ and nine of 33 were ST+. When 31 isolates were tested simultaneously with the Oxoid and the Pharmacia LT tests, 12 strains were LT+ by the Oxoid LT test but by the Phadebact LT test only seven of these strains were LT+ and, of the remainder, three gave uncertain results and two gave negative results. Of 69 porcine strains, seven were LT+ and three ST+. Of 901 human strains isolated in Hungary, 10 were LT+ and one of 24 tested was ST+. In two cases, ETEC strains were isolated from contacts of travellers returning from Mongolia and Bangladesh. Results of comparative studies with reference strains corresponded well to those of the classical toxin detection tests. The Oxoid test was rapid, sensitive, specific and easy to perform and is recommended for use in screening ETEC isolates. PMID- 1613779 TI - Adhesion of Shigella dysenteriae type 1 and Shigella flexneri to guinea-pig colonic epithelial cells in vitro. AB - Adhesion of bacteria to guinea-pig colonic epithelial cells in vitro was inhibited by fucose with all the four strains tested (two of Shigella dysenteriae type 1 and two of S. flexneri). N-acetyl neuraminic acid and N-acetyl mannosamine also caused inhibition, suggesting a multiplicity of receptors on the epithelial cell. Congo-red binding of the strains correlated with their adhesive ability, whereas haemagglutination of rabbit erythrocytes by the bacteria did not. PMID- 1613780 TI - Mechanism of persistent infection associated with peritoneal implants. AB - The ability of rabbits to clear an intraperitoneal injection of Pseudomonas aeruginosa in the presence or absence of a surgically implanted peritoneal device was investigated. Sham-operated rabbits without an implant eliminated a P. aeruginosa challenge of 5 x 10(6) cfu/ml; lavage fluid and peritoneal tissues became culture-negative within 96 h. However, peritonitis developed in rabbits that were given the same number of bacteria in the presence of an implant; high bacterial counts were recovered from the lavage fluid and the device itself. Scanning and transmission electronmicroscopy revealed bacterial biofilms on the surface of the device. Insertion of pre-colonised devices demonstrated a rapid multiplication of sessile organisms within the resulting bacterial biofilm. Counts reached a plateau of about 1 x 10(7) cfu/cm2 of Silastic by day 16 and fluctuated around this level until the end of the study. Pre-immunisation with formalin-killed whole cells of P. aeruginosa did not reduce this bacterial growth despite high levels of specific IgG. The results confirm the failure of peritoneal defences to clear an infection in the presence of an implant following either challenge with planktonic bacteria or insertion of a pre-colonised device, and demonstrate the rapid development of bacterial biofilms on the surface of the implant which appear to protect the bacteria from host defences, even when primed by pre-immunisation. PMID- 1613781 TI - Ribotyping of coagulase-negative staphylococci. AB - The discriminative capacity of ribotyping was initially assessed without knowledge of results obtained for the same isolates by use of more established typing methods. Forty-eight isolates of coagulase-negative staphylococci (CNS) from peritoneal fluids were studied. They were collected prospectively during 31 consecutive episodes of infection associated with peritoneal dialysis in 17 patients. DNA was digested by the restriction endonucleases EcoRI or HindIII and ribotyped by means of a biotinylated cDNA probe to 16S + 23S staphylococcal ribosomal RNA gene sequences. These methods in combination produced a total of 27 types which compared well with numbers of groups distinguished by other typing methods: limited biotype-antibiotic resistogram (ARB; 28), antibiotic resistogram alone (25), API-Staph (12), phage typing (9) and plasmid analysis (22). Ribotyping was highly reproducible and typed all isolates, including those that were not phage-typable (35) or did not contain plasmids (4). When used in a hierarchical manner with ARB, ribotyping results produced 13 additional types in comparison with the other three methods. When used hierarchically with all other typing systems, a further five types were found among isolates from two patients. However, some of the differences observed as a result of ribotyping could have been due to subtle changes produced by mutation, lysogenisation or gene transposition. Since the method requires additional time, expense and technical expertise, it is likely to be useful only when answers to specific epidemiological problems are required or as an initial screen before using other methods of genetic analysis. PMID- 1613782 TI - An ultrastructural study of Helicobacter mustelae and evidence of a specific association with gastric mucosa. AB - The ultrastructure of Helicobacter mustelae, a natural inhabitant of the ferret stomach, has been studied and compared with the human gastroduodenal pathogen H. pylori. H. mustelae is a short, slightly curved rod, 2 microns x 0.5 micron, with four or more sheathed flagella. The most common flagellar configuration is a single flagellum at one terminus, bipolar arrangement at the other end and a lateral flagellum. Dense inclusion bodies were observed below the flagellar insertion sites. It is suggested that this configuration is a specialised adaptation to motility in a viscous environment. On examination of the ferret gastric mucosa, similarities to H. pylori were observed such as adherence to gastric tissue and the formation of adhesion pedestals. However, unlike H. pylori, significant numbers of bacteria were intracellular. Furthermore, a much greater proportion of H. mustelae were attached to the mucosa with few bacteria lying free in the mucus, as is seen with H. pylori. It is concluded that the ferret is an important model for the study of adherence of bacteria to gastric mucosa and their possible role in peptic ulceration. PMID- 1613783 TI - Virulence and adhesive properties of serotypes A and B of Candida albicans isolated from paediatric burn patients. AB - The virulence and adhesive properties of 50 isolates of Candida albicans serotypes A and B collected over 6 years from 48 paediatric burn patients were examined to provide more detailed information about candidal pathogenesis in burn patients and to examine the relevance of the commonly used epithelial cell adhesion assay for determining fungal virulence. The isolates represented a fair distribution of serotypes (29 isolates were serotype A and 21 isolates were serotype B) and a total of 28 serotype-biotype combinations were found; 32% of the serotype-biotype combinations appeared only once, while 44% of the isolates showed similar biotype tests for two of three digits. Adhesion of the isolates to plastic and to buccal epithelial cells (BECs) was examined and compared after growth in a chemically defined medium. There were significant differences in the adhesion of individual isolates to plastic or BECs, but no correlation was found between biotype and adhesiveness. Serotype B isolates were found to be more adhesive to BECs (p less than 0.05) but not to plastic. There was no apparent correlation between candidal adhesiveness and site of isolation from these patients (autografts, blood, faeces, throat swabs, tracheal aspirates, wounds and intravenous catheters), although isolates from catheters were generally less adhesive to epithelial cells. Virulence in a systemic infection mouse model revealed that there were significant differences in virulence between isolates, but no correlation was found between virulence and the biotype, serotype or site of isolation. Similarly, no correlation was found between virulence and adhesiveness or cell-surface hydrophobicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613784 TI - Quantitative analysis of immunoglobulin G subclass responses to Pseudomonas aeruginosa antigens in cystic fibrosis. AB - The four subclasses of IgG have different structures, functions and implications in the antibody response. IgG subclass reactions to individual Pseudomonas aeruginosa structural antigens in 22 adolescents and young adults with cystic fibrosis (CF) were studied qualitatively and quantitatively by densitometric analysis of Western blot assays. These patients had been infected by P. aeruginosa for 7 years or longer and were divided into two groups according to their pulmonary status: Group 1 comprised 11 patients with relatively good pulmonary status; Group 2 consisted of 11 patients with poor pulmonary status. There was a relative decrease of IgG1 and a relative increase of IgG2 and, especially, of IgG3 and IgG4 antibodies against P. aeruginosa antigens in the CF patients. Comparison of the two CF patient groups showed a significant increase in the proportion of IgG3 in the Group 2 patients. This could be a potential cause or effect in the deterioration of their pulmonary function. Densitometric analysis of Western blots revealed more than 24 P. aeruginosa antigens and indicated those that were the targets of the isotype antibody response(s) that were apparently most harmful. Thus, there was a significant increase of IgG2 or IgG3 reactivity (or of both) against proteins F, H (H1 and H2), and I in the Group 2 patients. One other striking observation of this study was the high reactivity of IgG4 antibodies to protein H. IgG4 was the major antibody to this protein in seven of the 11 Group 1 patients compared to two of the 11 in Group 2. We hypothesise that IgG4 antibodies may antagonise IgG2 antibodies, helping to preserve stable pulmonary function. PMID- 1613785 TI - Ophthalmic laser surgery: therapeutic implications for the primary physician. AB - This paper represents the results of a retrospective study on the diagnosis and treatment of 102 consecutive patients who received laser surgery in a general ophthalmic practice during the period of August 1989 to September 1991. The purpose of the study is to document and interpret the type of eye disorders that lend themselves to definitive laser treatment. The goal of this article is to enhance the awareness of non-ophthalmologists in their pivotal and vital role in referring patients to an ophthalmologist for evaluation of the basic disease processes which, left untreated, can lead to vision impairment or blindness. PMID- 1613786 TI - Topological analysis of the hepatitis B virus core particle by cysteine-cysteine cross-linking. AB - The nucleocapsid, or core particle, of hepatitis B virus is formed by 180 subunits of the core protein, which contains Cys at positions 48, 61, 107 and 183, the latter constituting the C terminus. Upon adventitious oxidation, some or all of these cysteine residues participate in the formation of disulphide bridges, leading to polymerization of the subunits within the particle. To utilize the cysteine residues as topological probes, we reduced the number of possible intersubunit crosslinks by replacing these residues individually, or in all combinations, by serine. A corresponding set of variants was constructed within the context of an assembly-competent core protein variant that lacks the highly basic C-terminal region. Analysis, by polyacrylamide gel electrophoresis under non-reducing conditions, of the oxidative crosslinking products formed by the wild-type and mutant proteins expressed in Escherichia coli, revealed a clear distinction between the three N-proximal, and the C-terminal Cys: N-proximal Cys formed intermolecular disulphide bonds only with other N-proximal cysteine residues, leading to dimerization. Cys48 and Cys61, in contrast to Cys107, could be crosslinked to the homologous cysteine residues in a second subunit, and are therefore located at the dimer interface. Cys 183 predominantly formed disulphide bonds with Cys183 in subunits other than those crosslinked by the N-proximal cysteine residues. Hence, the polymers generated by oxidation of the wild-type protein are S-S-linked dimeric N-terminal domains interconnected via Cys183/Cys183 disulphide bonds. The intermolecular crosslinks between the N proximal cysteine residues were apparently the same in the C-terminally truncated and in the full-length proteins, corroborating the model in which the N-terminal domain and the C terminus of the HBV core protein form two distinct and structurally independent entities. The strong tendency of the N-terminal domain for dimeric interactions suggests that core protein dimers are the major intermediates in hepatitis B virus nucleocapsid assembly. PMID- 1613787 TI - Purification and crystallization of glycogen phosphorylase from Saccharomyces cerevisiae. AB - Glycogen phosphorylase from Saccharomyces cerevisiae is activated by the covalent phosphorylation of a single threonine residue in the N terminus of the protein. We have hypothesized that the structural features that effect activation must be distinct from those characterized in rabbit muscle phosphorylase because the two enzymes have unrelated phosphorylation sites located in dissimilar protein contexts. To understand this potentially novel mechanism of activation by phosphorylation, we require information at atomic resolution of the phosphorylated and unphosphorylated forms of the enzyme. To this end, we have purified, characterized and crystallized glycogen phosphorylase from S. cerevisiae. The enzyme was isolated from a phosphorylase-deficient strain harboring a multicopy plasmid containing the phosphorylase gene under the control of its own promoter. One liter of cultured cells yields 12 mg of crystallizable material. The purified protein was not phosphorylated and had an activity of 4.7 units/mg in the presence of saturating amounts of substrate. Yeast phosphorylase was crystallized in four different crystal forms, only one of which is suitable for diffraction studies at high resolution. The latter belongs to space group P4(1)2(1)2 with unit cell constants of a = 161.1 A and c = 175.5 A Based on the density of the crystals, the solvent content is 49.7%, indicating that the asymmetric unit contains the functional dimer of yeast phosphorylase. PMID- 1613788 TI - Aromatic-aromatic interactions in the zinc finger motif. Analysis of the two dimensional nuclear magnetic resonance structure of a mutant domain. AB - The folding and stability of globular proteins are determined by a variety of chemical mechanisms, including hydrogen bonds, salt bridges and the hydrophobic effect. Of particular interest are weakly polar interactions involving aromatic rings, which are proposed to regulate the geometry of closely packed protein interiors. Such interactions reflect the electrostatic contribution of pi electrons and, unlike van der Waals' interactions and the hydrophobic effect, may, in principle, introduce a directional force in a protein's hydrophobic core. Although the weakly polar hypothesis is supported by a statistical analysis of protein structures, the general importance of such contributions to protein folding and stability is unclear. Here, we show the presence of alternative aromatic-aromatic interactions in the two-dimensional nuclear magnetic resonance structure of a mutant Zn finger. Changes in aromatic packing lead in turn to local and non-local differences between the structures of a wild-type and mutant domain. The results provide insight into the evolution of Zn finger sequences and have implications for understanding how geometric relationships may be chemically encoded in a simple sequence template. PMID- 1613789 TI - Hybrid system for protein secondary structure prediction. AB - We have developed a hybrid system to predict the secondary structures (alpha helix, beta-sheet and coil) of proteins and achieved 66.4% accuracy, with correlation coefficients of C(coil) = 0.429, C alpha = 0.470 and C beta = 0.387. This system contains three subsystems ("experts"): a neural network module, a statistical module and a memory-based reasoning module. First, the three experts independently learn the mapping between amino acid sequences and secondary structures from the known protein structures, then a Combiner learns to combine automatically the outputs of the experts to make final predictions. The hybrid system was tested with 107 protein structures through k-way cross-validation. Its performance was better than each expert and all previously reported methods with greater than 0.99 statistical significance. It was observed that for 20% of the residues, all three experts produced the same but wrong predictions. This may suggest an upper bound on the accuracy of secondary structure predictions based on local information from the currently available protein structures, and indicate places where non-local interactions may play a dominant role in conformation. For 64% of the residues, at least two experts were the same and correct, which shows that the Combiner performed better than majority vote. For 77% of the residues, at least one expert was correct, thus there may still be room for improvement in this hybrid approach. Rigorous evaluation procedures were used in testing the hybrid system, and statistical significance measures were developed in analyzing the differences among different methods. When measured in terms of the number of secondary structures (rather than the number of residues) that were predicted correctly, the prediction produced by the hybrid system was also better than those of individual experts. PMID- 1613790 TI - Electron microscopy of decorated crystals for the determination of crystallographic rotation and translation parameters in large protein complexes. AB - The lumazine synthase/riboflavin synthase complex of Bacillus subtilis consists of an icosahedral capsid of 60 beta subunits enclosing a core of 3 alpha subunits. The preparation of reconstituted hollow capsids consisting of 60 beta subunits and their crystallization in a hexagonal (space group P6(3)22) and in a monoclinic (space group C2) modification have been described. The rotational and translational parameters of the protein molecules in both crystal forms were studied by electron microscopy of freeze-etch replicas and by Patterson correlation techniques. Decoration with silver and image processing provided images with the positions of the 3-fold and 5-fold molecular axes being labelled by metal clusters. This allowed the unequivocal determination of the orientation and translational position of the protein molecules with respect to the crystallographic axes in the hexagonal modification. From inspection of the decoration images it was immediately obvious that the hexagonal crystal forms of alpha 3 beta 60 and of beta 60 are isomorphous. In the monoclinic crystals, a local icosahedral 2-fold coincides with the crystallographic 2-fold axis. The exact solution of the particle orientation was determined by interpretation of Patterson self-rotation functions for the icosahedral symmetry axes. Rotational and translational parameters for the monoclinic modification are given. A rational procedure for the efficient application of freeze-etching techniques in order to elucidate the packing in crystals of large proteins is described. PMID- 1613791 TI - Solution conformations and aggregational properties of synthetic amyloid beta peptides of Alzheimer's disease. Analysis of circular dichroism spectra. AB - The A4 or beta-peptide (39 to 43 amino acid residues) is the principal proteinaceous component of amyloid deposits in Alzheimer's disease. Using circular dichroism (c.d.), we have studied the secondary structures and aggregational properties in solution of 4 synthetic amyloid beta-peptides: beta (1-28), beta-(1-39), beta-(1-42) and beta-(29-42). The natural components of cerebrovascular deposits and extracellular amyloid plaques are beta-(1-39) and beta-(1-42), while beta-(1-28) and beta-(29-42) are unnatural fragments. The beta (1-28), beta-(1-39) and beta-(1-42) peptides adopt mixtures of beta-sheet, alpha helix and random coil structures, with the relative proportions of each secondary structure being strongly dependent upon the solution conditions. In aqueous solution, beta-sheet structure is favored for the beta-(1-39) and beta-(1-42) peptides, while in aqueous solution containing trifluoroethanol (TFE) or hexafluoroisopropanol (HFIP), alpha-helical structure is favored for all 3 peptides. The alpha-helical structure unfolds with increasing temperature and is favored at pH 1 to 4 and pH 7 to 10; the beta-sheet conformation is temperature insensitive and is favored at pH 4 to 7. Peptide concentration studies showed that the beta-sheet conformation is oligomeric (intermolecular), whereas the alpha-helical conformation is monomeric (intramolecular). The rate of aggregation to the oligomeric beta-sheet structure (alpha-helix----random coil----beta-sheet) is also dependent upon the solution conditions such as the pH and peptide concentration; maximum beta-sheet formation occurs at pH 5.4. These results suggest that beta-peptide is not an intrinsically insoluble peptide. Thus, solution abnormalities, together with localized high peptide concentrations, which may occur in Alzheimer's disease, may contribute to the formation of amyloid plaques. The hydrophobic beta-(29-42) peptide adopts exclusively an intermolecular beta-sheet conformation in aqueous solution despite changes in temperature or pH. Therefore, this segment may be the first region of the beta peptide to aggregate and may direct the folding of the complete beta-peptide to produce the beta-pleated sheet structure found in amyloid deposits. Differences between the solution conformations of the beta-(1-39) and beta-(1-42) peptides suggests that the last 3 C-terminal amino acids are crucial to amyloid deposition. PMID- 1613792 TI - Three-dimensional structure of a recombinant variant of human pancreatic secretory trypsin inhibitor (Kazal type). AB - A modified version of the human pancreatic trypsin inhibitor (PSTI), generated in a protein-design project, has been crystallized in spacegroup P4(3) with lattice constants a = 40.15 A, c = 33.91 A. The structure has been solved by molecular replacement. Refinement of the structure by simulated annealing and conventional restrained least-squares yielded for 8.0 to 2.3 A data a final R-value of 19.1%. Differences to the known structures of porcine PSTI complexed with trypsinogen and modified human PSTI complexed with chymotrypsinogen occur at the flexible N terminal part of the molecule. These differences are influenced by crystal packing, as are low temperature factors for the binding loop. The geometry of the binding loop is similar to the complexed structures. PMID- 1613793 TI - Co-operative binding of the globular domain of histone H5 to DNA. AB - The globular domain of histone H5 (GH5) was prepared by trypsin digestion of H5 that was extracted from chicken erythrocyte nuclei with NaCl. Electron microscopy, sucrose gradient centrifugation, native agarose gel electrophoresis and equilibrium density gradient ultracentrifugation show that GH5 binds co operatively to double-stranded DNA. The electron microscopic images suggest that the GH5-DNA complexes are very similar in structure to co-operative complexes of intact histone H1 (or its variants) with double-stranded DNA, studied previously, which have been proposed to consist of two parallel DNA double helices sandwiching a polymer of the protein. For complexes with GH5 or with intact H1, naked DNA co-sediments with the protein-DNA complexes through sucrose gradients, and DNA also appears to protrude from the ends and sides of the complexes; measurements of the protein-DNA stoichiometry in fractionated samples may not reflect the stoichiometry in the complexes. An estimate of the stoichiometry obtained from the buoyant density of fixed GH5-DNA complexes in CsCl suggests that sufficient GH5 is present in the complexes for the GH5s to be in direct contact, as required by a simple molecular mechanism for the co-operative binding. Chemical crosslinking demonstrates that GH5s are in close proximity in the complexes. In the absence of DNA, GH5-GH5 interactions are weak or non existent. PMID- 1613794 TI - Crystallization and preliminary X-ray studies of the liganded lysine, arginine, ornithine-binding protein from Salmonella typhimurium. AB - The periplasmic binding protein LAO from Salmonella typhimurium, which is involved in lysine, arginine and ornithine transport, has been crystallized together with one of its ligands, arginine (LAO-Arg). Preliminary X-ray diffraction studies of LAO-Arg crystal show that it belongs to the orthorhombic space group P2(1)2(1)2(1) and has the unit cell dimensions of a = 37.65 A, b = 59.45 A, c = 115.91 A. Crystals of the LAO-Arg complex diffract beyond 2.0 A resolution. PMID- 1613795 TI - Crystallization and preliminary X-ray studies on the co-repressor binding domain of the Escherichia coli purine repressor. AB - The purine repressor is a putative helix-turn-helix DNA-binding protein that regulates several genetic loci important in purine and pyrimidine metabolism in Escherichia coli. The protein is composed of two domains, an N-terminal DNA binding domain and a C-terminal core that binds the purine co-repressors, guanine and hypoxanthine. The co-repressor binding domain (residues 53 to 341) has been crystallized from polyethylene glycol 600-MgCl2 solutions. They are of the monoclinic form, space group P2(1), with a = 38.2 A, b = 125.7 A, c = 61.8 A and beta = 100.2 degrees. They diffract to a resolution of at least 2.2 A and contain two monomers per asymmetric unit. The importance of the structural determination of this domain is underscored by the high degree of sequence homology displayed within the effector binding sites among a sub-class of helix-turn-helix proteins, of which LacI and GalR are members. The structure of the PurR co-repressor binding domain will provide a high resolution view of one such domain and could serve as a possible model for future effector site structural determinations. Perhaps more important will be this structure's contribution to the further understanding of how protein-DNA interactions are modulated. PMID- 1613796 TI - Crystallization and preliminary crystallographic study of neuraminidase from Micromonospora viridifaciens. AB - Single crystals of neuraminidase from the bacterium Micromonospora viridifaciens were obtained using the hanging drop vapour diffusion method and polyethylene glycol as precipitant at pH 5.0 or 5.5. The crystals belong to the orthorhombic space group P2(1)2(1)2(1), with unit cell dimensions a = 48.14 A, b = 82.73 A, c = 84.75 A and with one molecule in the asymmetric unit. Diffraction extends to at least 1.7 A. PMID- 1613797 TI - Initiating a crystallographic study of a class II fructose-1,6-bisphosphate aldolase. AB - We have reproducibly crystallized the metal-dependent Class II fructose-1,6 bisphosphate aldolase from Escherichia coli. Crystals in the shape of truncated hexagonal bipyramids have unit cell dimensions of a = b = 78.4 A, c = 290.6 A and are suitable for a detailed structural analysis. The space group has been identified as P6(1)22 or enantiomorph. Data sets to approximately 2.9 A resolution have been recorded using both the Rigaku R-AXIS IIc image plate area detector coupled to a copper target rotating anode X-ray source and using the MAR image plate systems with synchrotron radiation at the EMBL outstation DESY in Hamburg, and at S.R.S. Daresbury. Diffraction beyond 2.5 A has been observed when large freshly grown crystals are used with the synchrotron beam. A data set to this resolution has been collected. Several putative heavy-atom derivative data sets have also been measured using synchrotron radiation facilities and analysis of these data sets is in progress. PMID- 1613798 TI - De novo design, synthesis and study of albebetin, a polypeptide with a predetermined three-dimensional structure. Probing the structure at the nanogram level. AB - The de novo polypeptide named albebetin was designed to form the tertiary fold that has not yet been observed in natural proteins. The design was based on the molecular theory of protein structures. The gene coding for this polypeptide was chemically synthesized. For the initial characterization of a protein structure, a new approach has been developed that uses only nanogram amounts of a polypeptide without its previous purification. This approach includes the biosynthesis of radiolabeled protein in a cell-free translation system with subsequent analysis of its compactness and structure by size-exclusion chromatography, urea-gradient electrophoresis and limited proteolysis. According to all tests used, albebetin has a compact stable structure. PMID- 1613799 TI - Thermodynamic consequences of the removal of a disulphide bridge from hen lysozyme. AB - Differential scanning calorimetry experiments as a function of pH have been carried out for native hen egg white lysozyme and a three-disulphide derivative (CM6,127-lysozyme). The results indicate that the enthalpy (delta H298) and heat capacity changes (delta Cp) for unfolding are closely similar for the two proteins. This shows that the substantial reduction (25 degrees C at pH 3.8) in Tm resulting from removal of the 6-127 disulphide bond can, to a good approximation, be attributed totally to an increase in the entropy difference between the native and denatured states. The significance of this result for understanding the factors influencing the stability of folded proteins is discussed. PMID- 1613800 TI - Co-optimization of ribozyme substrate stacking and L-arginine binding. AB - A model of the Tetrahymena catalytic site predicts that nucleotide 262 (nt262) caps an RNA pocket in which nucleoside substrates and arginine-like competitive inhibitors reside. Here we show that substituted RNAs behave as if nt262 stacks on nucleoside substrates, supporting the model. The more frequent an nt262 is in natural sequences, the more reactive the corresponding Tetrahymena RNA is for both cognate and non-cognate nucleoside substrates. These more reactive RNAs with the majority nt262 also bind arginine more strongly, stereoselect more strongly in favor of L-arginine, and make a greater distinction between the somewhat similar side-chains of L-arginine and L-lysine. These parallel changes in interaction with nucleosides and arginine analogs seem best explained by stacking of the arginine's guanidino group under the nt262 base. One consequence is that selection for improved Tetrahymena catalysis with nucleosides should also yield an improved arginine site. PMID- 1613801 TI - Telomere end-replication problem and cell aging. AB - Since DNA polymerase requires a labile primer to initiate unidirectional 5'-3' synthesis, some bases at the 3' end of each template strand are not copied unless special mechanisms bypass this "end-replication" problem. Immortal eukaryotic cells, including transformed human cells, apparently use telomerase, an enzyme that elongates telomeres, to overcome incomplete end-replication. However, telomerase has not been detected in normal somatic cells, and these cells lose telomeres with age. Therefore, to better understand the consequences of incomplete replication, we modeled this process for a population of dividing cells. The analysis suggests four things. First, if single-stranded overhangs generated by incomplete replication are not degraded, then mean telomere length decreases by 0.25 of a deletion event per generation. If overhangs are degraded, the rate doubles. Data showing a decrease of about 50 base-pairs per generation in fibroblasts suggest that a full deletion event is 100 to 200 base-pairs. Second, if cells senesce after 80 doublings in vitro, mean telomere length decreases about 4000 base-pairs, but one or more telomeres in each cell will lose significantly more telomeric DNA. A checkpoint for regulation of cell growth may be signalled at that point. Third, variation in telomere length predicted by the model is consistent with the abrupt decline in dividing cells at senescence. Finally, variation in length of terminal restriction fragments is not fully explained by incomplete replication, suggesting significant interchromosomal variation in the length of telomeric or subtelomeric repeats. This analysis, together with assumptions allowing dominance of telomerase inactivation, suggests that telomere loss could explain cell cycle exit in human fibroblasts. PMID- 1613802 TI - Genomic organization and context of a trypanosome variant surface glycoprotein gene family. AB - We have defined the genomic organization and genomic context of a Trypanosoma brucei brucei gene family encoding variant surface glycoproteins (VSGs). This gene family is neither tandemly repeated nor closely linked in the genome, and is not located on small or intermediate size chromosomes. Two dispersed repeated sequence elements, RIME-ingi and the upstream repeat sequence, are linked to members of this gene family; however, the upstream repeat sequences are closely linked only to the basic copy. In other isolates of T.b. brucei this gene family appears conserved with some variation; a restriction fragment length polymorphism found among these isolates suggests the hypothesis that VSG genes may occasionally be diploid. A model accounting for both the generation of dispersed families of VSG genes, and for the interstrain variability of VSG genes, is proposed. PMID- 1613804 TI - Papers from the Ninth Annual Neurotrauma Society Meeting. New Orleans, Louisiana, November 9-10, 1991. Proceedings. PMID- 1613803 TI - Sequence divergence among members of a trypanosome variant surface glycoprotein gene family. AB - We have used analysis of DNA sequence data from four members of a Trypanosoma brucei variant surface glycoprotein gene family to investigate the molecular basis of the generation of antigenic diversity in African trypanosomes. Among these four sequences we find the greatest similarity in the untranslated sequences immediately upstream from the coding region. A complex pattern of nucleic acid and predicted amino acid sequence divergence appears starting at the coding sequence. Two related but highly divergent hydrophobic leaders are associated with different members of this gene family; both forms of these hydrophobic leaders appear to exist in other isolates of T. b. brucei. We find conservative replacements in the first 120 predicted amino acid residues of the mature protein; the following 80 predicted residues show less conservative replacements, and we suggest that this region may be hypervariable and exposed to the aqueous environment. PMID- 1613805 TI - Biochemistry and pharmacology of lipid antioxidants in acute brain and spinal cord injury. AB - Oxygen radical-mediated lipid peroxidation (LP) has been suggested increasingly to be an important factor in posttraumatic neuronal degeneration. Thus, numerous studies have evaluated the neuroprotective efficacy of pharmacological agents with lipid antioxidant activity in models of spinal cord and brain injury. Intensive pretreatment of animals with the endogenous lipid peroxyl radical scavenger vitamin E (i.e., alpha-tocopherol) has been shown to decrease posttraumatic spinal cord ischemia and to enhance chronic neurological recovery. However, the slow CNS tissue uptake of vitamin E requires chronic dosing, making it an impractical agent for treatment of acute neural injury. The glucocorticoid steroid, methyl-prednisolone (MP), has been shown to possess significant antioxidant efficacy and, when administered to animals or humans in antioxidant doses, improves chronic neurological recovery after spinal cord injury. This activity of MP is independent of the steroid's glucocorticoid receptor-mediated actions, as evidenced by the efficacy of the novel antioxidant 21-aminosteroids, which are devoid of glucocorticoid activity but have greater antioxidant efficacy than MP. One of these, tirilazad mesylate (U-74006F), has been shown to be effective in animal models of brain and spinal cord injury and is currently the subject of phase II clinical trials. Recently, compounds that combine the amino functionality of the 21-amino-steroids with the peroxyl radical scavenging chromanol portion of vitamin E (i.e., 2-methylaminochromans) also have shown promise as neuroprotective agents. The consistent benefit afforded by antioxidant compounds further supports the concept that LP is an important therapeutic target for acute pharmacological neuroprotection. PMID- 1613806 TI - The role of glutamate antagonists for the treatment of CNS injury. AB - Ischemic damage, chiefly of the focal type, and axonal disruption (diffuse axonal injury) are the major factors causing brain damage after human head injury. About one third of this damage may be delayed hours or days after the injury. Evidence from four animal models, each relevant to different aspects of human head injury, has shown that excitatory amino acid-induced changes are responsible for a proportion of the posttraumatic sequelae and that these effects can be blocked by EAA antagonists. This evidence is reviewed, and the implications for the conduct of human trials with EAA antagonists are discussed. PMID- 1613807 TI - The importance of brain temperature in cerebral injury. AB - The recent finding that small variations in brain temperature can critically determine the extent of histopathological injury in animal models of brain injury has generated renewed interest in hypothermic brain protection. Whereas mild hypothermia protects the brain from ischemic and traumatic brain injury, mild hyperthermia worsens ischemic outcome. Selective brain cooling has many advantages over whole body cooling, including the elimination of harmful side effects, such as cardiac arrhythmias. In addition to the clinical issue of brain protection, manipulating brain temperature has become a powerful tool with which to investigate the pathophysiology of ischemic and traumatic brain injury. The purpose of this article is to review and discuss recent findings demonstrating the importance of brain temperature in ischemic and traumatic brain injury. Potential mechanisms by which mild hypothermia may attenuate and mild hyperthermia accentuate the detrimental consequences of brain injury are reviewed. PMID- 1613808 TI - Systemic hypothermia in treatment of brain injury. AB - An extensive literature suggests that there are minimal complications of systemic hypothermia in humans at and above 30 degrees C for periods of several days. Intracranial hemorrhage has been found to complicate profound hypothermia (10-15 degrees C), and ventricular arrhythmias occur at temperatures below 30 degrees C. Our initial clinical studies were with 21 patients undergoing elective craniotomy cooled to 30-32 degrees C for 1-8 h (mean 4 h). Hypothermia was induced by surface cooling with water blankets. No complications were found. Among 11 patients with severe brain injury, cooling to levels below 32 degrees C was associated with ventricular arrhythmias in 1 patient and atrioventricular block in 1 patient. Asymptomatic hypokalemia was found routinely and treated with potassium replacement. No intracranial hemorrhage or other complications were found. With surface cooling, intravascular temperature dropped at 1.6 degrees C/h. Based on the safety of surface cooling to a core temperature of 32 degrees C for 48 h, we are conducting a randomized study of this level of hypothermia in patients with severe brain injury, cooled within 6 h of injury. PMID- 1613809 TI - Hypothermia in spinal cord injury. AB - Early investigations involving central nervous system (CNS) temperature lowering to protect against the detrimental effects of hypoxia and ischemia were based on the observation that hypothermia reduces brain metabolism and energy consumption. The protective effects of hypothermia have been demonstrated in numerous experimental models of cerebral ischemia and recently in models of brain trauma. These observations also led to the application of hypothermia, in the form of local spinal cord cooling (LSCC), in animal models of experimental spinal cord injury (SCI). Although some investigators have reported negative results in studies of LSCC following traumatic SCI, the majority of studies have noted beneficial effects. The favorable results in animal experimentation led to a limited number of cases where LSCC was used in the treatment of human SCI. However, results are difficult to interpret because (1) most investigators report only a small number of cases, (2) the studies lack a control population, (3) the time interval from injury to the application of cooling has been highly variable, and (4) several investigators combined drug treatments with LSCC. In these experiments, LSCC was achieved via perfusion with a cold solution or an epidural heat exchanger and the aim was to lower cord temperatures significantly (about 10 degrees C). The application of the technique itself is fraught with difficulties. It requires acute surgery in a traumatized patient, a wide multilevel laminectomy, and minimizing the time interval between injury and the application of spinal cord cooling. Recent studies in experimental brain ischemia strongly suggest that a drastic lowering of CNS temperature may be unnecessary to lessen the degree of tissue damage occurring following an ischemic brain injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613810 TI - Monosialogangliosides, neuroprotection, and neuronal repair processes. AB - Gangliosides play important roles in the physiologic operations of the nervous system, in particular that of the brain. Changes in ganglioside composition occur in the mammalian brain not only during development, but also in aging and in several neuropathologic situations. Gangliosides may modulate the ability of the brain to modify its response to signals from the surrounding environment. For example, cultured neurons respond to exogenous gangliosides with changes characteristic of differentiation; these sialoglycosphingolipids also amplify the response of neurons to neurotrophic factors. Additional in vitro studies have shown that monosialogangliosides like GM1 protect against excitatory amino acid related neurotoxicity by limiting the downstream consequences of receptor overstimulation. Systemic administration of GM1 is efficacious in reducing acute nerve cell damage and in facilitating medium- and long-term functional recovery following various types of injury to the adult mammalian central nervous system. The GM1 protective effects in the acute injury phase likely result, at least in part, from attenuation of excitotoxicity, while long-term functional recovery may reflect GM1 potentiation of neurotrophic factors. The potential therapeutic efficacy of GM1 is encouraged by recent positive clinical findings in acute human stroke, subarachnoid hemorrhage, and spinal cord injury. PMID- 1613811 TI - GM-1 ganglioside in human spinal cord injury. AB - Spinal cord injury is typically a devastating injury with no or only limited neurologic recovery. Recent papers have reported enhancement of neurologic recovery following spinal cord injury with both methylprednisolone and GM-1 ganglioside. This paper provides additional details of the GM-1 study and a further analysis of recovery of motor function for each of the ten neurologic levels assessed in the study. This additional analysis provides further evidence that the largest enhanced recovery of motor function in the GM-1 treatment group occurred in the muscles of the lower extremities and is consistent with the enhanced recovery occurring in the white matter tracts passing through the level of injury. PMID- 1613812 TI - A randomized trial of nimodipine in severe head injury: HIT I. British/Finnish Co operative Head Injury Trial Group. AB - We studied the efficacy of nimodipine in severely head-injured patients in a randomized study. Of 176 patients who received nimodipine, 2 mg/h iv for 2 day, 53% had a favorable outcome (moderate or good recovery). Of 175 control patients, 49% had a favorable outcome. This difference was not statistically significant but does not exclude the possibility that a study of a larger number of patients could show a clinically useful benefit. PMID- 1613813 TI - Intracellular acidosis in human and experimental brain injury. AB - Brain tissue acidosis is considered to play a role in the complex sequence of events following traumatic brain injury. This report reviews the experimental and clinical research conducted at the Medical College of Virginia to help clarify the extent of metabolic derangement that occurs and to evaluate the effect of treatment. Experimental injury models in ventilated animals showed that trauma produces a mild brain tissue acidosis that recovers within hours of injury. Hypoxia combined with trauma produces a relative ischemia and exacerbates the acidosis, which eventually resolves with resuscitation. Other studies revealed that CSF lactate measurements should be interpreted with caution, particularly in patients with subarachnoid hemorrhage. The results of two randomized clinical trials testing therapeutic effects of sustained hyperventilation and treatment with tromethamine (THAM) are discussed. PMID- 1613814 TI - Therapeutic potential for adenosine receptor activation in ischemic brain injury. AB - The present report reviews the biochemical and physiological responses to adenosine receptor activation and how these responses underlie the ability of adenosine to couple energy demand with energy supply. In addition, activation of adenosine receptors pharmacologically is shown to initiate various reactions which could be responsible for the observed adenosine-mediated attenuation of the neuropathological consequences of brain ischemia. Also reported is the extent to which side effects such as hypothermia can contribute to the observed efficacy of adenosine agonist administration in the small animal model of ischemia. Data from various in vitro and in vivo ischemia studies is presented showing that neuroprotection can be achieved following pharmacological activation of adenosine receptors either through agonists with high affinity for A1 adenosine receptors or drugs which potentiate endogenous adenosine levels. In general the data support utilization of adenosine receptor activation as a means of attenuating ischemic brain damage. PMID- 1613815 TI - Blood flow and metabolic therapy in CNS injury. AB - A hypermetabolic state, consisting of increased resting energy expenditure, excessive protein wasting, and hyperglycemia, occurs in patients with a severe head injury. The hypermetabolism can affect survival by rapidly resulting in protein-calorie malnutrition (increased energy expenditure and protein wasting) and may adversely affect neurological recovery by altering the microenvironment of the injured brain (hyperglycemia). PMID- 1613816 TI - Nicotinic and muscarinic subtypes in the human brain: changes with aging and dementia. AB - Different effects of normal aging on muscarinic and nicotinic receptor subtypes were observed in postmortem brain tissue from different regions of the human brain. A significant decrease in M1 and M2 receptors was found in cerebral cortex, while the M1 and especially the M2 receptors increased with age in the thalamus. A similar pattern of changes was also observed when using (-)3H nicotine as ligand for nicotinic receptors in the cortex and thalamus. No significant changes in nicotinic receptor binding were observed with age in the cortex or thalamus when using 3H-acetylcholine as ligand. Nicotinic and muscarinic receptors in the brain are not equally affected in dementia disorders. A marked loss of high affinity nicotinic receptors was observed in cortical tissue from patients with Alzheimer's disease and with multi-infarct dementia (MID). The muscarinic receptors were (both M1 and M2) increased in Alzheimer cortical tissue while they were decreased in MID. PMID- 1613817 TI - MPTP-induced parkinsonism: acceleration of biochemical and behavioral recovery by GM1 ganglioside treatment. AB - The effects of GM1 ganglioside administration on functional recovery and recovery of caudate nucleus dopamine levels have been assessed in cats made parkinsonian by administration of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP). Cats made severely parkinsonian by MPTP administration began to show spontaneous functional recovery by the third week after MPTP, as had been observed in previous studies with this model. In contrast, cats with similar initial impairment but which received 3 weeks of GM1 ganglioside treatment (30 mg/kg, i.p. daily) showed an accelerated behavioral recovery, showing significant functional improvement after the first week of GM1 treatment and almost normal function by the end of the third week of treatment. The GM1 treated cats had caudate nucleus dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and HVA levels significantly increased above levels measured in saline treated MPTP control cats. A second group of cats received MPTP only until the first signs of parkinsonism were observed and thus overall had a less severe initial syndrome than the cats described previously. Again, while all cats showed functional recovery over time, the recovery process was accelerated in GM1 treated cats. GM1 treatment also caused a significant increase in caudate dopamine levels in these cats. These results suggest that GM1 ganglioside administration can result in increased dopamine levels even in the heavily denervated striatum and accelerate functional recovery after an MPTP-induced lesion of the nigrostriatal dopamine system in the cat. This suggests that GM1 or other trophic factor therapies may be fruitful treatment strategies for a disorder of nigrostriatal function such as Parkinson's disease. PMID- 1613818 TI - The structural integrity of glial scar tissue associated with a chronic spinal cord lesion can be altered by transplanted fetal spinal cord tissue. AB - The potential for fetal spinal cord (FSC) tissue transplants to modify an established glial scar or to restrict the reformation of a scar following surgical manipulation of a chronic lesion site was studied in the injured rat spinal cord. Six to eight weeks after preparation of a hemisection lesion cavity, glial scar tissue was left intact in one group, whereas in a second group it was excised prior to transplantation of a suspension of FSC tissue. From the first group, examination of serial sections through the graft-host interface that had been immunoreacted for glial fibrillary acidic protein (GFAP) demonstrated that in many cases the glial scar no longer was a continuous wall separating the two tissues. Quantitation of the area occupied by these discrete gaps in the scar provided an Index of Fusion, indicating the extent of direct contact between the transplant and host spinal cord. In some animals this constituted as much as 60% of the interface, while in others there were no breaks in the scar (0% fusion). Reinjury of the spinal cord lead to a rapid astrocytic response culminating in the reestablishment of a dense matrix of glial cells and processes covered by a basal lamina. This reformed scar effectively isolated the spinal cord from the external environment of the cavity. When FSC tissue was transplanted after first removing scar tissue the continuity of reformed glial scarring at the graft-host interface was altered. Distinct gaps in the scar appeared randomly along the interface. The mean Index of Fusion for animals receiving a moderate reinjury (removal of scar tissue only) was not as high as for those animals in which a more severe reinjury (expansion of the cavity by 0.5 mm) was performed before transplantation. The extent of graft-host fusion was not significantly improved when scar tissue was removed prior to transplantation. These findings support the hypothesis that the presence of FSC tissue will have an effect on the persistence of glial scar tissue in a chronic lesion site as well as limit the extent to which a new scar is formed in response to a second injury to the spinal cord. PMID- 1613819 TI - Collagen IV is present in the developing CNS during Drosophila neurogenesis. AB - By means of immunocytochemistry with a battery of specific antibodies, we describe the expression of the collagen IV chain produced by the gene DCg1 during the two phases of Drosophila neurogenesis. DgC1 was not expressed in neuronal tissues as shown by in situ hybridization, but the onset of its expression in cells of mesodermal origin was concomitant with the appearance of collagen IV on early axon pathways and peripheral nerve roots in the embryonic developing CNS. A similar situation was found during imaginal CNS development at metamorphosis, when collagen IV immunoreactivity was detected on centrifugal and centripetal nerve pathways, and specially on retinula axons that develop from the eye imaginal disc towards the lamina anlage in the brain optic lobe. Our results strongly suggest that collagen IV could be involved, together with other informative molecules of basement membranes, in a dynamic process of cell-matrix interactions during the establishment of initial axon pathways and neurite outgrowth in vivo. PMID- 1613820 TI - Application of a fluorescent dye to study connectivity between third ventricular preoptic area grafts and host hypothalamus. AB - The mutant hypogonadal (hpg) mouse lacks a functioning gene for the neurohormone gonadotropin releasing hormone (GnRH). Previous studies from our laboratory had indicated that the initiation and maintenance of reproductive function in these mice could be brought about by the implantation of normal fetal grafts into adult hosts. Testicular or ovarian growth and other indicators of normal neurosecretory output were always accompanied by survival of GnRH neurons and growth of GnRH axons into the host median eminence where such axons terminate on the hypophysial portal capillaries. To determine if other connections exist between graft and the host hypothalamus, small crystals of the carbocyanine dye, 1,1'-dioctadecyl 3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI) were applied to either graft or host after fixation of the brain. Tissue sections were analyzed for retrograde and and anterograde movement of the dye. When crystals were placed on the graft, labeled axons were found in the host median eminence or in the host hypothalamus taking an arching trajectory toward the median eminence. Retrogradely labeled neurons in the host were few in number and largely confined to the host arcuate nucleus. With DiI crystals applied to the basal hypothalamus, labeled axons were distributed widely in the host but much sparser in the graft. Axons appeared to enter primarily at sites where the graft and host interface lacked an ependymal lining. Small numbers of retrogradely labeled neurons were also seen in the graft. Most were cells of very simple morphology and were distributed randomly in the graft. When double label experiments were carried out most DiI positive cells in the graft contained GnRH. These results indicate the connectivity between host hypothalamus and the third ventricular preoptic area grafts exists but is limited in nature. PMID- 1613821 TI - CG-4, a new bipotential glial cell line from rat brain, is capable of differentiating in vitro into either mature oligodendrocytes or type-2 astrocytes. AB - We have established a permanent cell line (CG-4) of rat central nervous system glial precursors from primary cultures of bipotential oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells, which were kept proliferating with the mitogen(s) secreted by the neuronal B104 cell line. The CG-4 cells have a normal karyotype and display the properties of normal O-2A cells. CG-4 cells can be propagated in serum-free culture medium supplemented with medium conditioned by B104 cells for unrestricted periods of time as O-2A cells, characterized by the presence of the A2B5 surface marker and the absence of markers specific for oligodendrocytes (galactocerebroside, myelin basic protein) or type 2-astrocytes (glial acidic fibrillary protein). bFGF and PDGF are potent mitogens for CG-4 cells and their combination can substitute for the B104-derived mitogen(s). CG-4 cells are capable of differentiating into either oligodendrocytes or type 2 astrocytes. Differentiation into oligodendrocytes occurs after withdrawal of the mitogen. Replacement of the mitogen with fetal calf serum (20%), in contrast, induces 50% of the CG-4 cells to differentiate into type 2-astrocytes. Pure cultures of oligodendrocytes or type 2-astrocytes can be generated in substantial amounts from CG-4 cells and maintained for several weeks in medium containing 5% fetal calf serum. PMID- 1613822 TI - Long-term survival of mouse corpus callosum grafts in neonatal rat recipients, and the effect of host sensitization. AB - Previous studies have suggested that the incidence of spontaneous rejection among immunogenetically mismatched neural transplants in neonatal recipients varies significantly depending on the cellular composition of the graft material. For example, neuron-rich grafts of embryonic mouse retina generally survive for extended periods without showing signs of rejection after implantation into neonatal rats, whereas cortical xenografts, which contain abundant glial and endothelial cells as well as neurons, typically undergo rejection 4-6 weeks after implantation. To determine whether the presence of donor glia is responsible for this high incidence of spontaneous rejection, we examined the fate of a non neuronal graft material composed predominantly of xenogeneic glial cells (post natal day 3, PD3, CD-1 mouse corpus callosum) implanted into the mesencephalon of PD1 Sprague-Dawley rats. The distribution and survival of donor astrocytes were assessed using a monoclonal antibody specific for a mouse astrocyte surface antigen, M2. Thirteen of 16 animals sacrificed within 2 months of implantation had detectable transplants. In these animals, M2-positive cells frequently migrated well away from body of the graft, clustering in large numbers in several characteristic regions of the host brain. Unlike cortical grafts of similar age, the vast majority (93%) of callosal transplants showed no histological signs of rejection or major histocompatibility complex antigen expression in and around the transplant-derived cells. As previously noted in the neonatal retinal transplant paradigm, however, well-integrated 1-month-old corpus callosum grafts could be induced to reject by appropriate sensitization of the host immune system, implying that the host was not immunologically tolerant to the foreign neural graft. With longer survival times in unsensitized hosts, a progressively smaller percentage of animals had detectable donor astrocytes (5 of 10 animals at 3 months postimplantation and 4 of 16 animals at 4 months); in those 9 animals with surviving grafts, only small numbers of M2-positive cells were seen within the graft bed and surrounding host brain. However, only 2 of the 26 "long-term" animals showed evidence of graft rejection. These results indicate that mouse astrocytes show characteristic patterns of migration into the host brain when implanted into neonatal rats; however, these xenogeneic cells have a limited duration of survival. The infrequency with which even subtle signs of spontaneous rejection were detected in animals that had received corpus callosum xenografts suggests that an immune-mediated process is unlikely to be responsible for the time-dependent elimination of the donor astrocytes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1613823 TI - A histochemical study of iron, transferrin, and ferritin in Alzheimer's diseased brains. AB - Immunohistochemical and histochemical staining were performed on Alzheimer's diseased brain tissue obtained at autopsy. The iron-regulatory proteins transferrin and ferritin as well as iron are, in general, found predominantly in oligodendrocytes similar to that previously reported for normal brain tissue. However, in the vicinity of senile plaques, the staining pattern is altered for both proteins and iron. Transferrin is homogenously distributed around the senile plaques and is apparently extracellular. In addition, transferrin is found in astrocytes in the cerebral cortical white matter of the Alzheimer's tissue rather than its normal distribution in oligodendrocytes. A robust ferritin immunoreaction accompanies senile plaques and many blood vessels in the Alzheimer's brain tissue. Although many ferritin-positive oligodendrocytes are present in the Alzheimer's tissue, most of the ferritin-containing cells associated with senile plaques and blood vessels are microglia. Iron can also be demonstrated in the senile plaques. The iron reaction product is observed both diffusely in proximity of the plaques and in cells associated with the plaques. These data strongly suggest a disruption in brain iron homeostasis in Alzheimer's disease as demonstrated by alterations in the normal cellular distribution of iron and the proteins responsible for iron regulation. These data will contribute to understanding both the potential for oxidative damage and the potential for metal neurotoxicity in Alzheimer's disease. PMID- 1613824 TI - Calmodulin antagonists chlorpromazine and W-7 inhibit exogenous cholesterol esterification and sphingomyelinase activity in human skin fibroblast cultures. Similarities between drug-induced and Niemann-Pick type C lipidoses. AB - In this report we showed that calmodulin antagonists chlorpromazine (CPZ) and W-7 (N-[6-aminohexyl]-5-chloro-1-naphtalenesulfonamide), when added to fibroblast cell cultures, gave rise to a time- and dose-dependent decrease of sphingomyelinase activity. CPZ and W-7 also significantly inhibited LDL- and non LDL-dependent cholesterol esterification. Addition of these drugs to cell culture medium mimicked what is observed in the genetic disease Niemann-Pick type C. H-7 (1-[5-isoquinonylsulfonyl]-2-methylpiperazine), an inhibitor of protein kinase C and cyclic nucleotide-dependent kinases, had no effect on sphingomyelinase and cholesterol ester formation. Thus the possibility of a modulation of cell sphingomyelin and cholesterol esters by a calmodulin-dependent second messenger system must be considered. PMID- 1613825 TI - Calbindin-D28K and ischemic damage of pyramidal cells in rat hippocampus. AB - An antibody against rat calbindin-D28K, a calcium-binding protein present at high concentration in certain neurons of the central and peripheral nervous systems, was used to determine the progression of the pathological events in the rat hippocampus following experimental cerebral ischemia. Calbindin-D28K immunoreactivity is present in dentate granule cells and in the CA1-CA2 pyramidal cells. CA1 subfield contains a higher proportion of calbindin-D28K-positive pyramidal cells than does the CA2 subfield and CA1 cells are more immunoreactive than the CA2 cells. The pyramidal cells of the CA1 and CA2 subfields are vulnerable to ischemia. The cells in the CA1 became necrotic within 3-4 days after ischemia while those of the CA2 became necrotic within 2 days. There was a concomitant decrease in calbindin-D28K immunoreactivity in the whole hippocampal regio superior after ischemia which peaked 3 days postischemia. The difference in CA2 and CA1 vulnerability seemed to be inversely correlated with the calbindin D28K contents of the CA2 and CA1 pyramidal cells. The decrease in the calbindin D28K contents of these neurons was accompanied by cell damage. We therefore suggest that calbindin-D28K is an important factor for the survival of pyramidal cells in the hippocampal formation after ischemia. PMID- 1613826 TI - Prevention of hand injuries in cycle accidents. AB - More than one fifth of patients in a group involved in cycle crashes sustained hand injuries. The average time off work as a result of the hand injury in our study was 17.6 days. The number and severity of hand injuries would be reduced by the wearing of proper gloves and this is recommended. The gloves currently sold as "cycling" gloves are not adequate. PMID- 1613827 TI - Tumor necrosis factor and cardiac function. AB - The direct effect of tumor necrosis factor (TNF), a product of activated macrophages, on myocardial performance was determined using an isolated papillary muscle technique and a modified Langendorff preparation. Papillary muscle was obtained from male adult rats 4-5 hours after they received either 100 ng/kg TNF (group A), or 100 micrograms/kg TNF (group B) or saline (control). Group B animals exhibited significantly greater peak tension development and velocity of contraction compared with controls (p less than 0.05). In group A animals these variables were not significantly different from those of the controls (p greater than 0.05). Electrophysiologic measurements revealed a significant decrease in resting membrane potential in both group A and group B animals compared with the controls (p less than 0.05). Whole hearts perfused with serum from animals treated with TNF 18-22 hours earlier exhibited significant impairment of contractility, decreased rate of systolic pressure development, and decreased rate of relaxation compared with the controls (p less than 0.05). Coronary flow and myocardial water content were similar for both groups of perfused hearts. These data suggest that tumor necrosis factor stimulates an early beneficial effect on myocardial function, which 18-22 hours later is associated with impairment of myocardial performance. This effect appears to be serum transferable. PMID- 1613828 TI - Long-term follow-up of vascularized bone grafts for the reconstruction of tibial nonunion: evaluation with computed tomographic scanning. AB - Ten cases of reconstruction of the tibia with vascularized bone grafts were evaluated by computed tomographic (CT) scanning. In all cases the grafts were placed because of pseudarthrosis. The patients ranged in age from 20 to 64 years. The duration of follow-up was 1-9 years. In six cases fibular grafts were used to bridge the defect and in four cases iliac crest grafts were used. No additional bone grafts were placed after the initial operation. The pseudarthroses were classified into three types: type N--no bony defect (4 cases); type P--partial bony defect (3 cases); and type C--complete segmental bone loss (3 cases). Our evaluation showed that the grafts used to treat the type N and type P pseudarthroses were the same shape and size as at the time of placement. The grafts used to treat the type C pseudarthroses were hypertrophied, although the medullary canal of the graft remained the same size as at the time of placement. Hypertrophy was a result of an extraperiosteal reaction. The fibular grafts were square rather than triangular in cross section. It was concluded that mechanical loading is important in promoting hypertrophy of the graft. PMID- 1613829 TI - Effect of recombinant human growth hormone on catabolic hormones and free fatty acids following thermal injury. AB - Severe burn injury elicits the release of catabolic hormones that contribute to negative nitrogen balance, protein wasting, and impaired wound healing. Previous studies have shown that burn patients receiving recombinant human growth hormone (rhGH) therapy have an increase in the rate of skin donor site healing and a shorter hospital stay. The mechanism by which rhGH exerts its effects, however, is not clearly understood. This study examines the effects of rhGH on circulating levels of catabolic hormones and nonesterified fatty acids in pediatric burn patients. Patients with greater than 40% total body surface area burn were randomly assigned to receive placebo (n = 8) or 0.2 mg/kg/day rhGH (n = 6) throughout their hospitalization. All patients had early morning blood samples assessed for catecholamines (CAT), cortisol, insulin, glucagon, and free fatty acid (FFA) levels during a period of hypermetabolism. No differences could be demonstrated in age, burn size, postburn day of evaluation, resting energy expenditure per kilogram, respiratory rate, heart rate, respiratory quotient, serum cortisol, and serum glucose between placebo- and rhGH-treated patients. The rhGH-treated group did show a significant elevation (p less than 0.05) in insulin like growth factor-1 (55.9 +/- 14.5 vs. 168 +/- 23.7 mU/mL), total catecholamines (1,817 +/- 177 vs. 1,117 +/- 137 pg/mL), norepinephrine (1,257 +/- 121 vs. 867 +/ 113 pg/mL), epinephrine (385 +/- 175 vs. 147 +/- 36 pg/mL), insulin (32.8 +/- 3.3 vs. 25.0 +/- 3.0 mU/mL), glucagon (215 +/- 18 vs. 158 +/- 22 pg/mL), and free fatty acids (0.74 +/- 0.01 vs. 0.59 +/- 0.04 mEq/L) compared with the placebo group (data expressed as mean +/- SE).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613830 TI - Hemorrhagic hypotension after brain injury causes an early and sustained reduction in cerebral oxygen delivery despite normalization of systemic oxygen delivery. AB - Morbidity and mortality are doubled when hemorrhagic hypotension (HEM) accompanies a traumatic brain injury (TBI). Hemorrhagic hypotension initiates a "secondary" injury (SI) that has been attributed to ischemia, but this has not been confirmed in the laboratory. All previous studies have been of relatively short duration (less than 6 hours), allowing insufficient time to study the pathophysiology of SI, since maximal intracranial pressure (ICP) elevations may occur 16 to 20 hours after injury. We hypothesized that HEM combined with TBI would reduce cerebral oxygen delivery (cO2del) and cerebral metabolic rate for oxygen (cMRO2) to a greater degree than would occur with TBI alone. In a porcine model of TBI and HEM we recorded systemic oxygen delivery (sO2del), ICP, cerebral blood flow (CBF), cO2del, cMRO2, brain oxygen extraction ratio (cO2ER), and cortical water content (CWC) over a 24-hour study period. Controls (n = 7) were instrumented only, group 1 (n = 14) received a focal cryogenic lesion only, group 2 (n = 21) received a cryogenic lesion plus hemorrhage to 50 mm Hg for 45 minutes. Animals were resuscitated with crystalloid solutions; shed blood in group 2 animals was returned after one hour. Hemorrhagic hypotension following TBI produced a significant and sustained reduction in cO2del associated with a lower cMRO2 and cO2ER, and higher ICP and CWC, than seen with lesion alone. This occurred despite adequate early restoration of sO2del. This confirms that cerebral ischemia is ongoing despite restoration of systemic hemodynamics. PMID- 1613831 TI - Simultaneous liver and lung injury following gut ischemia is mediated by xanthine oxidase. AB - We have previously shown that gut ischemia/reperfusion (I/R) causes simultaneous liver and lung dysfunction and that neutrophils play a critical role in this process. The purpose of this study was to ascertain whether xanthine oxidase (XO) was likewise operational. Normal and XO-inactivated rats (given a tungsten enriched, molybdenum-depleted diet for 3 weeks) underwent 45 minutes of occlusion of the superior mesenteric artery, and control rats were subjected to a sham laparotomy. After zero and six hours of reperfusion, blood was sampled and livers and lungs harvested. Iodine-125-labeled albumin leak was used as a marker for pulmonary and liver capillary permeability barrier function, and serum acetoacetate/3-hydroxybutyrate (AcAc/3-OHB) levels as an index of hepatic mitochondrial redox state. Gut ischemia/six hours of reperfusion (I/R) increased the 125I albumin lung/blood ratio and the 125I albumin liver/blood ratio; AcAc/3 OHB levels decreased significantly. Xanthine oxidase activation eliminated the observed lung and liver capillary leak as well as the hepatic metabolic derangement induced by gut I/R. In conclusion, the simultaneous lung and liver dysfunction produced by gut I/R is mediated by XO. PMID- 1613832 TI - Can adult trauma surgeons care for injured children? AB - Large urban trauma centers care for injured children as well as adults in many areas of the country, but the quality of care in these hospitals has not been evaluated versus that available at pediatric trauma centers. The recent validation of TRISS methodology in pediatric populations allowed us to evaluate the quality of pediatric trauma care being provided in a level I trauma center treating injured patients of all ages. We reviewed the records of 353 injured children (aged 0-17 years) who were admitted to our trauma center over a 30-month period for the following data: demographics, mechanism of injury, initial physiologic status (RTS), surgical procedures required, need for intensive care, nature and severity of the injuries (ISS), and outcome. TRISS analysis allowed us to compare our population with the Major Trauma Outcome Study. Only two of the 21 total deaths (overall mortality, 6%) were unexpected, and there were seven unexpected survivors. One hundred twenty-one patients underwent emergency surgical procedures and 63 required admission to the intensive care unit. The Z scores ranged from +0.32 for the children aged less than 2 years to +3.98 for the older age group (14-17 years). We conclude that the quality of care for pediatric trauma patients admitted to trauma centers that care for patients of all ages compares favorably with national standards. In most areas of the country, improvements in pediatric trauma care will likely come from addressing the special needs of injured children in general trauma centers rather than from developing separate pediatric facilities. PMID- 1613833 TI - Vascular injuries in a rural state: a review of 978 patients from a state trauma registry. AB - The demographics, etiology, and outcome of 1148 vascular injuries suffered by 978 patients reported from eight trauma centers in a largely rural state to a trauma registry (NCTR) data base containing 26,617 patients entered over a 39-month time interval were analyzed. Vascular injury patients were more frequently transferred by helicopter (18%), referred from other hospitals (45%), transfused more blood (8 units mean/24 hours), had higher mean ISS values (14 vs. 9), had lower systolic blood pressures on admission (113 vs. 128 mm Hg), had higher emergency department mortality (3.3%), and required immediate surgery more often (79%) when compared with nonvascular injury NCTR patients (p = 0.0001). Vascular injury patients had significantly longer hospital stays (13 vs. 10 days), longer ICU stays (5 vs. 4 days), and greater hospital costs ($22,500 vs. $12,300) while incurring more serious AIS values for the regions of the chest, abdomen, and extremities. One hundred twenty-nine (13.1%) died, 97 after admission compared with a 6.2% mortality for NCTR nonvascular injury victims. Forty-seven percent of vascular injuries were extremity lesions; the amputation rate was 1.3%; and management was most often by simple repair (41.9%) or patching (22.2%). Rural vascular injury patients had a high incidence of blunt trauma (43.4%) and were older (average, 51 years); they were transported by helicopter more often (30.3%) and were frequently referred from another hospital (77.8%); they had longer ICU, ventilator, and hospital stays and greater hospital charges; and they had higher mortality (14.2%) compared with urban vascular trauma victims. The data suggest a need for the trauma care system to focus on earlier recognition, stabilization, and rapid transportation of this most seriously injured group of patients. PMID- 1613834 TI - Prospective comparison of clinical judgment and APACHE II score in predicting the outcome in critically ill surgical patients. AB - Prospective identification of patients who will not survive has been proposed as a means of limiting utilization of medical resources including critical care. This study prospectively compared prediction of outcome for surgical ICU patients by clinical assessment and the APACHE II score. Five hundred seventy-eight patients were assessed within 24 hours of admission by the ICU attending physician and predicted to live or die. An APACHE II score was calculated in that same time period. All data were stored in a data base and compared with actual SICU outcome. There were 40 deaths in 578 patients (6.9%). The clinical assessment had an overall accuracy of 95.2% vs. 90.9% for APACHE II. The Pearson correlation coefficients for the two methods of prediction were 0.59 for clinical assessment and 0.44 for APACHE II. Predictive power was not greatly improved by combining both prediction methods. Over 40% of patients predicted to die by both methods actually survived. This study demonstrates that clinical assessment is superior to APACHE II in predicting outcome in this group of surgical patients, although the difference is small. In addition, this study suggests that neither clinical assessment nor the APACHE II score, when obtained within 24 hours of admission, is very reliable at predicting which surgical ICU patients will die. PMID- 1613835 TI - Neurologic consequences of cerebrovascular injury. AB - Because of ongoing controversy, the issue of vascular repair or ligation for patients with cerebrovascular injuries and preoperative central neurologic deficits is frequently debated. A total of 133 patients with penetrating cerebrovascular injuries were analyzed. The frequency of preoperative neurologic deficit was 20% (27 patients). The common carotid and internal carotid arteries were the most frequently injured structures, with a 29% and 15% incidence of preoperative neurologic deficits, respectively. The results of carotid repair in all patients whose preoperative deficit was limited to weakness or paralysis were favorable (seven patients normal or improved, two patients unchanged). The results of repair in patients whose preoperative deficit was characterized by obtundation were variable (four patients improved, four patients worsened or died). The results of carotid ligation were also variable (one improved, one unchanged, three worsened or died). Limited numbers of patients with preoperative neurologic deficits and the retrospective nature of this review prohibit definite conclusions. Therefore a multicenter, prospective, randomized trial of ligation or vascular repair for comatose patients with cerebrovascular injuries is proposed. PMID- 1613836 TI - The use of transesophageal echocardiography in the evaluation of chest trauma. AB - Transesophageal echocardiography (TEE) has been used over the last 10 years (1982 1992) to study the heart and thoracic aorta. We set out to evaluate the diagnostic applications of TEE in patients with thoracic trauma. Specifically, TEE was performed on patients suspected of having either a cardiac contusion or an injury of the thoracic aorta. Fifty-eight patients admitted with thoracic trauma underwent TEE. Fifty of those patients suspected of having a cardiac contusion also underwent transthoracic echocardiography (TTE). The two diagnostic modalities were compared. In 21 of these patients a wide mediastinum was apparent on admission chest x-ray films. Nineteen of this latter group underwent thoracic angiography in addition to TEE. Two patients underwent post-mortem examination. Of the 50 patients undergoing both TEE and TTE, a cardiac contusion was detected by TEE in 26 patients. Transthoracic echocardiography detected only six contusions in this group. Of the 21 patients with a wide mediastinum, TEE detected three obvious aortic disruptions. These findings were confirmed in each case by angiography. In 16 cases TEE showed the aorta to be normal. This was confirmed on the angiogram in 14 cases and by autopsy in two cases. Transesophageal echocardiography revealed an aortic intimal irregularity distal to the left subclavian artery in two cases. The results of aortography were normal in these last two cases. As a diagnostic modality, TEE more accurately detected cardiac contusions than TTE (p less than 0.001) and was a very sensitive screening tool in the early evaluation of patients with a wide mediastinum. PMID- 1613837 TI - Oxygen extraction ratio: a valid indicator of transfusion need in limited coronary vascular reserve? AB - We have described whole body oxygen (O2) extraction ratio (ER) as a reliable indicator of transfusion need in acute normovolemic anemia. In normal hearts, myocardial lactate production (-LACT), indicating anaerobic metabolism, does not occur until the ER greater than 50% and Hct less than 10%. It is not known if the ER is valid in the setting of limited coronary vascular reserve. This study assesses the effect of a critical left anterior descending (LAD) coronary stenosis on the compensation to acute blood loss anemia. Adult dogs were anesthetized, paralyzed, and mechanically ventilated. A critical LAD stenosis was created in seven animals (STEN). There were seven controls (CON). Animals underwent isovolemic exchange transfusion with 6% HES until cardiac failure (CF). Catheters were placed in the aorta, pulmonary artery, and anterior interventricular coronary vein. Cardiac failure occurred at Hct = 8.6% +/- 0.4% in the CON and 17.0% +/- 0.5% in the STEN animals. Cardiac output increased in the CON, but not in the STEN animals. Blood flow in the LAD increased in the CON but not the STEN animals. -LACT began in the CON and STEN animals at Hct less than 20% and coincided with an ER greater than 50% in both groups. We conclude that CF occurs at a higher hematocrit with a critical LAD stenosis. The whole body ER greater than 50% remains a valid indicator of myocardial metabolism in anemia in the presence of limited coronary vascular reserve. The ER may be a useful guide to transfusion therapy. PMID- 1613838 TI - Emergency center thoracotomy: impact of prehospital resuscitation. AB - Emergency center thoracotomy was performed at our facility on 389 patients from 1984 through 1989. There were no patients excluded from the study, and survival for all patients was 8.3% with survival rates of 15.2% and 7.3% for stab and gunshot wounds, respectively. Emergency center thoracotomy was performed on 42 patients suffering from isolated extrathoracic injuries with 7% survival. There were no survivors of blunt trauma in this study. Fifty-three percent of the patients arrived with cardiopulmonary resuscitation (CPR) in progress. The average time of prehospital CPR for survivors was 5.1 minutes compared with 9.1 minutes for nonsurvivors. Of the survivors, prehospital endotracheal intubation prolonged successful toleration of CPR to 9.4 minutes compared with 4.2 minutes for nonintubated surviving patients (p less than 0.001). Emergency center thoracotomy is useful in the resuscitation of victims dying of penetrating truncal trauma. Prehospital endotracheal intubation significantly lengthened the time of successful CPR. PMID- 1613839 TI - Emergency thoracotomy: survival correlates with physiologic status. AB - Emergency thoracotomy is a standard procedure in the management of cardiac arrest in patients sustaining severe trauma. We examined the records of 463 moribund trauma patients treated at our institution from 1980 to 1990 to refine indications for emergency thoracotomy. Patients underwent thoracotomy either in the emergency department (ED) (n = 424) or in the operating room (OR) (n = 39) as a component of continuing resuscitation after hospital arrival. The survival rate was 13% (61 of 463) overall, 2% (3 of 193) for blunt, 22% (58 of 269) for all penetrating, 8% (10 of 131) for gunshot, 34% (48 of 141) for stab-wound patients, and 54% (21 of 39) for patients who underwent emergency thoracotomy in the OR. Survival correlated with the physiologic status of patients both on initial evaluation in the field by paramedics and on arrival at the ED. Patients with penetrating trauma and in profound shock (BP less than 60 mm Hg) or mild shock (BP 60-90 mm Hg) with subsequent cardiac arrest had survival rates of 64% (27 of 42) and 56% (30 of 54), respectively. None of the patients with absent signs of life, defined as full cardiopulmonary arrest with absent reflexes (n = 215), on initial assessment by paramedics in the field, survived. We conclude that (1) no emergency thoracotomy should be performed if no signs of life are present on the initial prehospital field assessment; (2) emergency thoracotomy is an indicated procedure in most patients sustaining penetrating trauma; (3) blunt traumatic cardiac arrest is a relative contraindication to emergency thoracotomy. PMID- 1613840 TI - Dorsal carpometacarpal dislocation of the index finger: a report of three cases and a review of the English-language literature. AB - Isolated dorsal carpometacarpal dislocation of the index finger is a rare injury. We treated three patients with such an injury; two cases by delayed open reduction and internal fixation, and one case by direct closed reduction and internal fixation. Satisfactory functional results were obtained in two of the three cases (follow-up of 4 and 2 years, respectively). Anatomic factors, the mechanisms of injury, and management as discussed in the English-language literature are reviewed. PMID- 1613841 TI - Technical note: modifications and improvements of the Milch technique for the reduction of anterior dislocation of the shoulder without premedication. AB - A method for the reduction of anterior dislocations of the shoulder based on the Milch technique is presented. We have been using this method for the last 2 years (75 dislocations) with excellent results. The reduction is easy, produces minimal pain and discomfort for the patient, and the success rate is as high as 94.5%. The modified Milch technique is less troublesome for the patient and the physician and we strongly recommend it. PMID- 1613842 TI - Acute epiglottitis: historical highlights and perspectives for future research. AB - Acute epiglottitis was classified under more than 35 headings before 1960. It is the purpose of this article to review and examine the crucial events that have marked, but also often impeded, the conceptualization of this disease. As is the case for other diseases, the history of acute epiglottitis depended upon the evolution of technology in medicine. From this review the author has produced a "catalogue raisonne" of material snatched from the immensity of obsolete publications. It can be considered as an overview of the historical highlights of this very peculiar disease, acute epiglottitis. It also stresses areas of potential research, as our medical forefathers had imagination but lacked the technical capabilities which are now at our disposal. Finally, it gives the reader a unique opportunity to glance at the making of otolaryngology. PMID- 1613843 TI - Quantitative light microscopy in urological oncology. PMID- 1613844 TI - Choice of gastroepiploic vessels for gastrocystoplasty. AB - Use of vascularized gastric segments for augmentation cystoplasty and for construction of a continent urinary diversion depends on adequate blood supply via the right or left gastroepiploic vessels. Inadequate gastroepiploic vessels on 1 side may not be apparent without intraoperative testing for their patency. We recommend routine testing for the patency of the left and right gastroepiploic vessels before selecting the side to be used as a pedicle for the gastric segment. PMID- 1613845 TI - Improved pump placement with infrapubic penile prosthetic implantation. AB - A common problem with implantation of an inflatable penile prosthesis is inadequate placement and/or fixation of the pump mechanism. We report on a total of 45 of our most recent patients who underwent penile prosthesis implantation for erectile dysfunction. In all cases the implants were placed with an infrapubic approach in conjunction with a penoscrotal counterincision for improved pump placement and fixation. One patient (2.2%) had an infectious complication requiring revision. When we compared this infection rate with the infectious complication rates reported in the literature, we found that adding a penoscrotal counterincision did not increase the risk of infectious complication to the patient. PMID- 1613846 TI - Detrusor function with lesions of the conus medullaris. AB - Conventional urodynamic evaluation is unable to distinguish between a pure conus lesion and one with concomitant cauda equina involvement. Lumbosacral evoked potentials to tibial nerve stimulation assesses the sensory root and dorsal horn interneurons of the L5 to S2 spinal cord segments. This allows for the diagnosis of a pure lesion of the conus medullaris with preservation of the sensory root response (R wave) with absence of the dorsal horn gray matter response (S wave). Urodynamic evaluation in 5 patients with a conus lesion showed a variety of detrusor responses ranging from hyperreflexia through areflexia with decreased compliance to areflexia with normal compliance. The ability to diagnose a pure conus lesion may have prognostic significance as newer modalities of treatment emerge, all of which require intact gray matter of the spinal cord. PMID- 1613847 TI - The influence of anterior root stimulation (S2) in deafferented spinal cord injury men on cavernous electrical activity. AB - Registration of cavernous electrical activity (single potential analysis of cavernous electrical activity) was recently suggested for the diagnosis of autonomic cavernous dysfunction. For validation of this method the effect of sacral neurostimulation on cavernous electrical activity was examined. In 3 male patients with a complete spinal cord lesion (T3, T4 and T12, respectively), deafferentation was done at the S2 to S5 levels. Around the anterior roots of S2 to S5 electrodes for neurostimulation were placed. Cavernous electrical activity was recorded with an intracavernous needle electrode and with surface electrodes in the flaccid as well as in the erect states induced by neurostimulation (at 7, 8, 12, 18, 20, 30 and 45 Hz., 30 v. and 0.4 msec). In all patients similar potentials compared to the normal values, as well as additional pathological potentials were recorded during flaccidity. During neurostimulation all patients achieved full erection with no or markedly decreased cavernous electrical activity to frequencies of 12, 18, 20 and 30 Hz., while to 7, 8 and, more pronounced, 45 Hz. only partial erection with ongoing cavernous electrical activity was found. Our study strongly suggests that cavernous electrical activity and, subsequently, the cavernous smooth muscle tone are dependent on autonomic input. This finding supports the hypothesis that single potential analysis of cavernous electrical activity may be valid in the diagnosis of cavernous autonomic dysfunction. Furthermore, our results suggest a possible role for single potential analysis of cavernous electrical activity in the fine tuning of erection inducing neurostimulators. PMID- 1613848 TI - Continent appendicocolostomy: a variation of the Mitrofanoff principle in pediatric urinary tract reconstruction. AB - There are numerous options for continent urinary reconstruction in children. If the appendix is available and the bladder capacity is satisfactory, a Mitrofanoff procedure may be performed using the appendix as a catheterizable tube implanted into the bladder. However, in many patients the bladder is absent or too small for this type of reconstruction. An alternative technique, termed appendicocolostomy, is to implant the appendix under the tenia of a detubularized patch of cecum or sigmoid colon, which becomes part of a continent neobladder or is attached to the bladder itself. This procedure has been used in 12 children and 1 adult undergoing continent reconstruction. Urological diseases included bladder exstrophy (10 patients) and a neuropathic bladder (3). Two patients underwent undiversion of a sigmoid conduit, while in 7 of the remaining patients the bladder was included in the reservoir. In 1 patient histological examination of the tip of the appendix revealed an incidental invasive carcinoid tumor necessitating appendectomy and revision of the reconstruction. Otherwise, no complications have occurred. Three adults were scheduled for this procedure but the appendix was diseased and an alternative form of diversion was necessary. Followup ranged from 2 months to 4 years. All patients are totally dry with a capacity of 300 to 750 cc (mean 475 cc). The appendicocolostomy is a superior form of conduit reconstruction that should be considered when the appendix is available during continent reconstruction. However, in adults the appendix may be fibrotic, precluding its use. Because most boys with exstrophy and a small bladder capacity requiring augmentation cystoplasty must perform intermittent catheterization, attachment of the appendix to the reservoir is an alternative that allows for easier and less painful intermittent catheterization than catheterization of the reconstructed epispadiac penis. PMID- 1613849 TI - Contrast-induced central nervous system toxicity after radiographic evaluation of the lower urinary tract in myelodysplastic patients with ventriculoperitoneal shunts. AB - Routine urological evaluation of children with myelomeningocele helps to identify those at risk for upper urinary tract deterioration. We report on 2 patients with ventriculoperitoneal shunts who had intraperitoneal rupture of the bladder. Reflux of contrast media via or around the ventriculoperitoneal shunt into the cerebral ventricles occurred in both patients, resulting in severe neurological insult. PMID- 1613850 TI - The predictive value of ultrasonography in evaluation of infants with posterior urethral valves. AB - Between 1981 and 1989, 28 infants less than 6 months old with posterior urethral valves underwent ultrasound evaluation as part of the initial evaluation at our hospital. The single ultrasound feature that correlated with subsequent renal function was the status of corticomedullary differentiation. The presence of corticomedullary junctions in at least 1 kidney in 17 infants was always associated with a serum creatinine level of 0.8 mg./dl. or less in long-term followup. Of 11 patients with absent corticomedullary differentiation 7 had eventual creatinine levels of greater than 0.8 mg./dl. with 5 of them suffering clinically significant renal insufficiency. An association between vesicoureteral reflux and absent corticomedullary junctions was also found. PMID- 1613851 TI - Prognosis for patients with prenatally diagnosed posterior urethral valves. AB - Children in whom posterior urethral valves are diagnosed shortly after birth are at higher risk for renal failure than children in whom posterior urethral valves are diagnosed later in life. The influence of prenatal diagnosis of posterior urethral valves on clinical outcome has not been established. We collected data on children with posterior urethral valves treated since birth at our hospital between 1975 and 1990. The clinical outcomes for 8 patients diagnosed prenatally and 15 diagnosed neonatally were compared. Of the 8 patients in the prenatal group 5 (64%) had renal failure compared to 5 of 15 (33%) in the neonatal group (p greater than 0.05). Nadir creatinine of more than 1.2 mg./dl. correlated with the development of renal failure in all patients in the neonatal and prenatal groups. There was 1 death in the prenatal group. In our experience prenatal diagnosis of posterior urethral valves has grave implications, including a 64% incidence of progressive renal failure and a 64% incidence of transient pulmonary failure. Oligohydramnios and postnatal pulmonary insufficiency are predictive of progressive renal failure. Earlier diagnosis and treatment of children with posterior urethral valves did not improve the clinical prognosis. PMID- 1613852 TI - The treatment of urinary incontinence in children using glutaraldehyde cross linked collagen. AB - Periurethral injection of polytetrafluoroethylene (PolyTef) paste has been used to correct urinary incontinence for 2 decades. The controversy over distant migration of the paste has led to an interest in alternative materials particularly for the pediatric patient. Glutaraldehyde cross-linked collagen, derived from bovine dermal collagen, is effective in treating urinary incontinence in adults. Eight children with structural urinary incontinence underwent glutaraldehyde cross-linked collagen injection. Fluorourodynamic studies preceded and followed the injections. An average of 10.9 cc glutaraldehyde cross-linked collagen was injected per treatment (range 2.5 to 20). The number of injections per child ranged from 1 to 6 (mean 2.1) and followup averaged 13.75 months (range 6 to 33). Overall, 88% of the patients were cured or improved: 5 (63%) became continent, 2 were improved and 1 had no effect. PMID- 1613853 TI - Primary endodermal sinus tumor of the penis: a case report. AB - We report a case of primary extragonadal germ cell tumor of the penis in a 2-year old child with elevated serum alpha-fetoprotein. The patient responded well to a combination of bleomycin, etoposide and cisplatin, achieving a complete response within 3 cycles. He was alive and disease-free 8 months after diagnosis. To our knowledge this is the first case of an endodermal sinus tumor of the penis reported in the literature. The possible histogenesis of this tumor at such a rare site is discussed. PMID- 1613854 TI - Acute bilateral testicular torsion in the adolescent. AB - A case of acute bilateral testicular torsion in the adolescent is reported. This case reaffirms the need to perform bilateral scrotal exploration in cases of suspected torsion. Although it represents an extreme rarity, delay in exploration may have resulted in bilateral orchiectomy. The case also appears to be another example of intermittent testicular pain as a harbinger of impending torsion in a patient with the bell clapper deformity. Perhaps a more aggressive approach should be taken to explore patients surgically who present with intermittent scrotal pain. PMID- 1613855 TI - Bilateral primary neuroblastomas in the inguinal canal. AB - The incidental finding of a nodular mass in the inguinal canal in children usually occurs during surgical exploration for an inguinal hernia. We report an unusual occurrence of neuroblastomas bilaterally and simultaneously in the inguinal canals of an infant with no evidence of metastatic disease. PMID- 1613856 TI - Spontaneous regression of metastases in a case of bilateral renal cell carcinoma. AB - A patient is described who had undergone bilateral nephrectomy for renal cell carcinoma and who had been maintained on hemodialysis for the last 2 years. A total of 3 months after acceptance into the program he was found histologically to have metastatic pleural lesions, which had regressed spontaneously 1 1/2 years ago. Repeat clinical and radiological assessment has shown no tumor recurrence. PMID- 1613857 TI - Fast magnetic resonance imaging in the evaluation of tumoral obstructions of the inferior vena cava. AB - A prospective study was conducted on 9 patients with suspected obstruction of the inferior vena cava on ultrasonography, dynamic computerized tomography and/or inferior venacavography during the course of a retroperitonal tumor to assess the value of magnetic resonance imaging with gradient echo sequences. The findings on gradient echo magnetic resonance imaging were compared with the other imaging modalities and surgical or necropsy results. Our results suggest that gradient echo magnetic resonance imaging is the most appropriate imaging modality to diagnose and delineate the extent of inferior vena caval obstruction. PMID- 1613858 TI - Inflammatory pseudotumor of the bladder. AB - Inflammatory pseudotumor of the bladder is an unusual benign lesion arising from the bladder submucosa. We present 2 cases and describe the clinical presentation, and radiographic and histological findings. This benign lesion must be differentiated histologically from several malignant lesions of the bladder. Complete surgical excision, either by transurethral resection or partial cystectomy, appears to be curative. PMID- 1613859 TI - Restenosis of the urethra despite indwelling Wallstent. AB - Of 5 patients with recurrent urethral strictures were treated with a self expandable permanently implanted urethral stent 2 had stenosis within the stent 2.5 and 9 months after placement of the stent, respectively. PMID- 1613860 TI - False diagnoses of venous leak impotence. AB - Tests for erectile dysfunction using intracavernous injections of vasoactive drugs are currently popular and have resulted in frequent diagnoses of venous leak impotence. Tests used to make this diagnosis, however, have not been validated by study in control subjects. We present 2 cases of false diagnoses of venous leak impotence. Anxiety mediated through the sympathetic nervous system may block the action of intracavernous smooth muscle relaxants. The resulting incidence of false diagnoses of venous leak impotence is unknown. PMID- 1613861 TI - Three cases of didmoad or Wolfram's syndrome: urological aspects. AB - We report on 3 patients with the rare syndrome of diabetes insipidus, diabetes mellitus, optic atrophy, neurosensory deafness, atony of the urinary tract and other abnormalities (DIDMOAD or Wolfram's syndrome). All 3 patients had diabetes mellitus, optic atrophy, deafness and dilatation of the urinary tract. In 2 patients there was diabetes insipidus. The possibility of anatomical outlet obstruction or a neurogenic bladder was eliminated radiologically and urodynamically, and dilatation of the urinary tract was considered to be either a consequence of high diuresis associated with diabetes insipidus or a degenerative process affecting the central and peripheral nervous system, which can explain all of the manifestations of the syndrome except diabetes mellitus. A significant improvement in bilateral urinary tract distention was achieved by bladder drainage in the first 2 cases, while desmopressin therapy dramatically decreased the daily urinary output. PMID- 1613862 TI - The presence of an antibacterial glycoprotein in a spectrum of transitional gel carcinomas. AB - The mucin lining of the bladder is thought to serve as a primary defense mechanism against bacterial colonization, and has recently been implicated in the urothelial resistance to carcinogenic insult. We have isolated a unique glycoprotein fraction (GP1) of this lining from the normal rabbit bladder which may have a function in preventing bacterial adherence and colonization in the urinary tract. This glycoprotein has been shown to bind to a wide range of uropathic bacteria. The present study examines changes in the bladder's antibacterial defense mechanisms as measured by GP1 expression in the neoplastic state. Using an anti-GP1 serum, immunohistochemical staining was performed on 20 paraffinized and fresh frozen transitional cell carcinomas ranging from low grade, superficial tumors to high grade, invasive tumors. The presence of GP1 was seen throughout the mucosal layer in normal specimens with increased amounts noted towards the mucosal surface. Progressively decreased expression was noted with increasing grades of all transitional carcinoma specimens. Mucosal field changes in GP1 expression were not noted in any of the patients. Intestinal mucosal controls failed to detect the presence of GP1. These studies suggest that the expression of GP1 decreases with tumor dedifferentiation and that bladder tumorogenesis may serve a role in handicapping the bladder's primary antibacterial defense mechanism. PMID- 1613863 TI - Effect of outlet obstruction on 3H-thymidine uptake: a biochemical and radioautographic study. AB - Experimental outlet obstruction in the rabbit is characterized by a rapid and substantial increase in urinary bladder mass. Although it is clear that both the smooth muscle and connective tissue compartments are increasing in mass, there is little information on the mechanisms by which this increase in mass occurs. As an initial investigation in this process, urinary bladders from normal and obstructed NZW rabbits were exposed in vitro to tritiated thymidine (3H-TdR) in order to determine which populations of cells are induced to synthesize DNA following outlet obstruction, and when, after obstruction, such synthesis occurs. Biochemical analysis of nucleic acids was performed on each specimen to determine total and radioactive DNA. These analyses showed a marked increase in DNA synthesis at 24 hours following obstruction which remained relatively high through seven days after obstruction. There was a decline in labelling at 14 days. Incorporation of radioactive label peaked at three days and declined to control levels by 14 days. Samples of tissue were taken from each subject and processed for radioautography. At 24 hours after obstruction, significant numbers of cells of the basal cell layer of the urothelium are observed to be actively involved in DNA synthesis, while the other two tissue compartments (muscularis and connective tissue) show no significant changes when compared to normal specimens. Connective tissue, on the other hand, showed significantly increased levels of labelling above control level from three to 14 days after obstruction. Smooth muscle cells were observed to be frequently labelled in only one of the experimental bladders observed three days after obstruction. PMID- 1613864 TI - Characterization of bovine bladder mucin fractions that inhibit Escherichia coli adherence to the mucin deficient rabbit bladder. AB - We have previously shown that a dialyzed, lyophilized saline extract from bovine urothelium can restore the antiadherence activity of the rabbit bladder following mucin removal with 50% acetone. This report describes results of initial purification of antiadherence factor(s) from bovine bladder mucin and describes results of biochemical analysis in an attempt to elucidate possible mechanism of this antiadherence activity. Separation performed by gel filtration (Spectra gel AcA 34, 20-350 KD range) results in three fractions. Only the low molecular weight fraction had a statistically significant inhibitory effect on bacterial adherence to the mucin deficient rabbit bladder. After overnight dialysis against running deionized water and lyophilization, the crude extract contained 60% protein while gel filtration fractions 1-3 contained 35%, 90% and 15% by weight respectively. The first fraction (apparent high molecular weight, greater than 350 kD) did not appear to enter SDS polyacrylamide electrophoresis gels (SDS PAGE, 3-12%) or agarose gels (0.5%) to any significant extent. In the fractions that displayed antiadherence activity (the crude extract, fractions 2 and 3) SDS PAGE bands were seen corresponding to an apparent molecular weight of 78 kD in addition to bands co-migrating with bovine serum albumin (BSA). BSA itself slightly increases bacterial adherence in this model. Most of the albumin of the crude extract was found in the second fraction (60%). On the other hand most of the sulfate and sugar of the crude extract was found in the third, low molecular weight fraction. Since sulfated polysaccharides such as heparin and dextran sulfate are very effective antiadherence agents in this rabbit bladder model, it is conceivable that the sulfated sugar content of the third fraction is responsible for its antiadherence effect on the mucin deficient rabbit bladder. PMID- 1613865 TI - A pharmacological in vitro study of the mouse urinary bladder at the time of acute change in bladder reservoir function after irradiation. AB - Mouse urinary bladder strips were investigated as to whether the acute change in bladder reservoir function seen after irradiation might be due to major changes in basic nerve and smooth muscle functions. The release mechanism of acetylcholine, cholinergic and non-cholinergic nerve activation explored by indomethacin and potassium channel activation were investigated. It was concluded that the normal mouse bladder is partly cholinergically and partly non cholinergically innervated. The role of acetylcholine is of the same importance as in other rodents. However, it was not possible to distinguish any difference between normal and irradiated mouse bladders in respect to nerve and smooth muscle function. PMID- 1613866 TI - Extracorporeal shock wave lithotripsy for patients with calcified ipsilateral renal arterial or abdominal aortic aneurysms. AB - A total of 4 patients with renal or upper ureteral calculi associated with ipsilateral calcified renal arterial or abdominal aortic aneurysms underwent extracorporeal shock wave lithotripsy. One patient with a renal artery aneurysm had a solitary kidney. Linear distance from the calcified aneurysm to the stone, calculated by computerized and plain tomography, ranged between 4.6 and 6.5 cm. (mean 5.3). Treatment was accomplished on an unmodified Dornier HM3 lithotriptor using 900 to 2,400 shock waves (mean 1,575) at 18 kv. There were no complications of treatment and all 4 patients were discharged from the hospital within 24 hours, at which time radiographic examination revealed excellent stone comminution without change in the calcified aneurysm. With followup as long as 30 months, no adverse effects of therapy have become evident. We conclude that the presence of an ipsilateral calcified aneurysm may not necessarily preclude treatment of renal or upper ureteral calculi with extracorporeal shock wave lithotripsy, although further studies are required to help define the potential limits of such therapy in this setting. PMID- 1613867 TI - Cystometry in mice--influence of bladder filling rate and circadian variations in bladder compliance. AB - Meaningful interpretation of cystometric measurements in experimental animals requires detailed analysis of factors that could affect the results. In the present study, the effect of catheter size and bladder filling rate were studied in detail; in addition, the influence of (day) time on bladder compliance was assessed by cystometry in mice. Bladder reservoir function was independent of the catheter size, when i.v. cannulae with outer diameters of 0.6 and 0.8 mm. were used, but leakage pressure and leakage volume were increased with the larger catheter. Neither the storage capacity nor the bladder wall resistance showed dependence on filling rates above 0.1 ml./min. Below this rate, bladder capacity increased and wall resistance decreased with decreasing filling rate. Furthermore, leakage eventually occurred below 20 mm. Hg with the lower filling rates. Marked diurnal variations in bladder compliance and wall resistance were observed. Maximum storage capacity was observed at 7 p.m. and the reservoir function subsequently decreased to a plateau between 1 a.m. and 1 p.m. PMID- 1613868 TI - Implantable penile venous compression device: initial experience in the acute canine model. AB - We have designed a venous compression device implantable at the base of the penis outside the tunica albuginea. Because it does not require exposure of individual veins for ligation, the risk to the cavernous nerve is practically nil. It occludes the venous return only temporarily, and thus collaterals are less likely to occur. In this preliminary acute study in dogs (N = 13), the penile venous compression device was shown to be effective and safe in controlling penile venous drainage and maintaining rigid erection. PMID- 1613869 TI - A comparison of stone damage caused by different modes of shock wave generation. AB - A standard stone phantom was used to compare stone damage after extracorporeal shock wave administration from electrohydraulic, electromagnetic and piezoelectric lithotripters. For each machine, a low and high shock wave intensity setting was chosen: 18 & 24 kV for electrohydraulic; 16 & 19 kV for electromagnetic; power levels 1 and 4 for piezoelectric. The shock wave was focused either at the front (surface facing the wave source) or back surface of the stone and 50, 100, 200 or 400 shocks were delivered to different stone groups. Effects of varying physical properties in the stone phantom were also investigated. Stone damage was described in terms of volume loss and both depth and width of the resulting damage crater. At the lower intensity settings, all three machines produced stone volume loss which was linearly related to the number of shock delivered. At higher intensity settings, volume loss increased rapidly as the number of shocks increased. With the same number of shocks, stone volume loss was greatest with the electrohydraulic machine, followed by electromagnetic and piezoelectric lithotripters for both low and high intensity settings. Damage craters from the piezoelectric device were narrow and deep; those from the electromagnetic machine were of the shape of a right angle circular cone; whereas those from the electrohydraulic lithotripter were shallow and wide. At the high intensity settings, damage from the piezoelectric and electrohydraulic lithotripters appeared to depend upon the position of the focal point with a higher volume loss when the shock waves were targeted at the front surface of the stone. For the electromagnetic device, a higher volume loss was found when we positioned the focal point at the back surface of the stone phantom. Stone phantoms with lower mechanical strength and acoustic impedance were more easily damaged than those with higher values. Finally, a computer regression model was developed to express volume loss in terms of the intensity setting, focal position and number of shocks for each lithotripter. PMID- 1613871 TI - Entubulization repair of severed cavernous nerves in the rat resulting in return of erectile function. AB - Erectile dysfunction is a significant complication of radical pelvic surgery in men. Using the rat as an experimental model, we investigated the feasibility of repairing surgically ablated cavernous nerves utilizing silastic tube nerve growth conduits filled with nerve growth enhancing media. Known fertile male Sprague-Dawley rats were randomly divided into four surgical groups consisting of nerve ablation, immediate nerve reconstruction utilizing the entubulization technique (two groups) and control. The nerve ablation group had five mm. sections of the cavernosal nerve excised bilaterally. The entubulization nerve graft group had five mm. sections of the cavernous nerve excised bilaterally, followed by immediate microsurgical reconstruction with a silastic nerve tube conduit filled with either Matrigel and heparin (MA) or Matrigel and heparin plus acidic fibroblast growth factor (MA/aFGF), interposed between the severed cavernous nerve stumps bilaterally. The control group underwent sham operations with the cavernous nerves being exposed only. Erectile function was evaluated at one, two, and four months postoperatively. Return of erectile function was defined as tumescence of the corporal bodies with application of direct electrical stimulation (four volts of five millisecond pulses at 20 Hertz) to the proximal cavernous nerves. The two and four month electrical stimulation studies resulted in tumescence from 50% and 58% of the entubulization nerve reconstructed nerves with MA/aFGF versus 29% and 30% for the MA only group and only 5% and 11% for the ablated group, respectively. We conclude that in this experimental model immediate nerve graft repair utilizing entubulization techniques with the addition of nerve growth enhancing media appears to be a successful method of salvaging erectile function when the cavernous nerves have been divided. PMID- 1613870 TI - Studies on the afferent and efferent renal nerves following autotransplantation of the canine kidney. AB - The presence of both afferent and efferent renal nerves following renal transplantation was investigated in a canine autotransplant model. The efferent postganglionic sympathetic renal nerves were studied using the glyoxylic acid histofluorescence technique to identify renal tissue adrenergic amines (Grade 0 4). The afferent sensory renal nerves were studied by the systemic blood pressure response to renal arterial injection of capsaicin. In 8 control dogs with native innervated kidneys (Group I), intrarenal injection of capsaicin significantly increased the systemic blood pressure from baseline by 32.4 +/- 6.3 mm. Hg (p less than 0.01). This response was equivalent to the blood pressure increase following injection of capsaicin into the mesenteric artery which was 37.3 +/- 9.8 mm. Hg. The renal tissue histofluorescence grade in this group was 4. Six dogs were studied two to three weeks after autotransplantation of a solitary kidney (Group II). Intrarenal injection of capsaicin did not increase the systemic blood pressure in these animals. Three dogs in this group had no evidence of renal tissue adrenergic amines by histofluorescence (Grade 0); the remaining two animals had renal tissue histofluorescence grades of 1 and 2. Eight dogs were studied 12 to 35 months after autotransplantation of a solitary kidney (Group III). Intrarenal injection of capsaicin in these animals significantly increased the systemic blood pressure from baseline by 10 +/- 1.4 mm. Hg (p less than 0.001). The renal tissue histofluorescence grade in this group ranged from 1 to 3. These data support the presence of both afferent and efferent renal nerves in the kidney at greater than or equal to one year post-transplant. PMID- 1613872 TI - Comparative autonomic responses of the cat and rabbit bladder and urethra. AB - The cat and the rabbit have both been utilized extensively in the study of lower urinary tract function. Previous studies have demonstrated that although both the cat and rabbit bladder are approximately the same weight, the in-vitro cat bladder can generate over 6 times the intravesical pressure of the rabbit bladder. The current study was designed to compare the ability of the isolated bladder to generate pressure with the pressures required to maintain flow through the isolated urethra for both the cat and the rabbit. The results can be summarized as follows. 1) The cat bladder is visibly much thicker than the rabbit bladder, and in vitro cystometry demonstrates that it is far less compliant than the rabbit bladder. 2) Over 20 cm.H2O pressure is required to begin flow through the isolated cat urethra preparation, whereas 5 cm.H2O begins flow through the rabbit urethra. 3) Increasing the flow rate (up to 7-fold) through both the isolated cat and rabbit urethra increases intraurethral pressure only slightly. 4) Both the isolated cat and rabbit urethra respond strongly to field stimulation and alpha-adrenergic stimulation (relative to the opening pressure required to begin flow), but not to cholinergic stimulation. 5) Field stimulation following pre-stimulation by methoxamine induces a strong relaxation of the pre-stimulated cat urethra, but an additive contraction in the pre-stimulated rabbit urethra. These studies demonstrate that in order for the cat to empty its bladder, it must generate a comparatively high intravesical pressure, whereas the rabbit is required to generate a relatively low intravesical pressure. PMID- 1613873 TI - Optimal parameters for CO2 laser reconstruction of urethral tissue using a protein solder. AB - This study was designed to determine the optimal laser parameters for welding urethral tissue and to develop further understanding of the welding process. A partial transection of the pendulous rat urethra was repaired using laser powers of 80, 120, and 160 milliwatts with shutter speeds of 50 milliseconds, 100 milliseconds, and in a continuous wave mode. Repairs were made using the laser alone and the laser plus a protein solder. Measurements of intraluminal bursting strength, percentage stricture and histology were performed. The highest bursting strength with the least amount of tissue damage was achieved using a power of 120 milliwatts with 100 milliseconds pulses and the addition of a protein solder. The average percentage stricture was lowest with the laser plus solder repair (4.2%) when compared to laser only repair (14%). Intraluminal bursting strength was similar in both types of repairs. Histology demonstrated marked changes in collagen organization after laser application in all models. PMID- 1613874 TI - Conservative surgery of renal cell tumors in 140 patients: 21 years of experience. AB - Operative method, course and complications were analyzed retrospectively in 140 patients who underwent a conservative operation for renal tumor between June 1969 and December 1990. In 53 patients (20 women and 33 men, mean age 61.2 years, range 38 to 77 years, with 49 renal cell carcinomas and 4 benign renal tumors) there was an imperative indication for an organ preserving operation because nephrectomy would have made dialysis obligatory. In 87 patients (29 women and 58 men, mean age 53.7 years, range 27 to 74 years, with 72 renal cell carcinomas and 15 benign renal tumors) the tumor was conservatively resected in the presence of a normal contralateral unit (elective indication) and 68 of these patients (78%) were symptom-free. In the imperative group 32 of 49 patients (65.3%) with renal cell carcinoma had no evidence of disease after a mean followup of 4.6 years. Known metastases were present in 4 of 7 patients who died of the tumors in this group. In 3 patients with an imperative indication for conservative surgery a second tumor occurred in the kidney: 2 were treated with further parenchyma sparing operations, while in 1 with poor physical condition no further measures were possible. Of 72 patients with renal cell carcinoma who underwent an elective operation 68 (94.4%) had no signs of tumor progression after a mean followup of 3.3 years. One patient died of tumor metastases, and 2 (2.7%) had tumor recurrence in the kidney requiring nephrectomy and enucleation, respectively. The 5-year cause-specific survival rates for the imperative and elective groups were 84% and 96%, respectively. Patients with a local stage T3 tumor were characterized by a significantly worse survival curve than those with a stage T1 or T2 tumor but no significant difference was noted among the various grades of differentiation. PMID- 1613875 TI - Transitional cell carcinoma of the renal pelvis and ureter: prognostic relevance of nuclear deoxyribonucleic acid ploidy studied by slide cytometry: an 8-year survival time study. AB - In 72 patients with urothelial carcinoma of the renal pelvis or ureter the ploidy, deoxyribonucleic acid (DNA) heterogeneity and counts of cell cycle phases in the tumor were analyzed by means of single cell DNA cytophotometry with the intention of finding new prognostic factors in addition to those already known (stage and grade). Followup ranged from 1 to 8 years. The results of the DNA analyses were related to the tumor categories, histopathological grading of the tumors and clinical course. Malignancy grade 1 tumors showed DNA frequency peaks in the diploid range, while tumors assessed as malignancy grade 2 showed heterogeneous DNA distribution patterns. Malignancy grade 3 tumors exhibited 71% aneuploid and 29% tetraploid DNA values. The proliferation rate of the tumor cells was statistically significantly higher in malignancy grades 2 and 3 than in malignancy grade 1. The prognosis for grade 1 tumors is good, whereas it is unfavorable in the case of grade 3 tumors. For these 2 groups (patients with grades 1 and 3 tumors) DNA ploidy affords no additional prognostic information. Grade 2 tumors, on the other hand, are heterogeneous in respect to DNA ploidy although they exhibit the same histomorphological degree of differentiation. These tumors can be subclassified as aneuploid (biologically aggressive) and diploid or tetraploid (biologically less aggressive) tumors. There was also a positive correlation between T category and DNA ploidy. The cell lines were aneuploid in 38% of the patients with stage T1 tumors, 56% with stage T2 tumors and almost 85% with stage T3, N+ tumors. A significant correlation was found between the results of DNA cytophotometry and the clinical course of the disease. Patients with diploid tumor cell nuclei had no metastases and no local tumor progression for up to 8 years, whereas patients with aneuploid tumor cell nuclei suffered metastasis and local tumor progression within 24 to 36 months. The patients died of the tumor 36 months after primary diagnosis on the average. The determination of DNA ploidy, tumor heterogeneity and tumor cell proliferation by means of DNA cytophotometry affords valuable clues as to prognosis. PMID- 1613876 TI - Complications following unstented parallel incision extravesical ureteroneocystostomy in 1,000 kidney transplants. AB - Between May 10, 1982 and September 1, 1990, 1,000 kidney transplant recipients underwent parallel incision extravesical ureteroneocystostomy for urinary tract reconstruction. Complications attributed to this surgical technique that required reoperation occurred in 2.1% of the recipients. These complications included urinary extravasation in 9 patients, ureteral necrosis in 3, ureteral obstruction in 3, ureteral bleeding in 3, ureteral implantation into thickened folds of peritoneum in 2 on chronic ambulatory peritoneal dialysis and ureteral implantation into an ovarian cyst in 1. Vesicoureteral reflux occurred in 0.4% of the ureteroneocystostomies, none of which was revised. No allografts were lost as a result of these complications. The principles of the technique are sound. One should be careful if the patient has a small, defunctionalized or scarred bladder, has undergone multiple pelvic operations or has had pelvic inflammatory disease. PMID- 1613877 TI - The frequency of histopathological abnormalities in incidental appendectomy in urological patients: the implications for incorporation of the appendix in urinary tract reconstruction. AB - In 1980 Mitrofanoff described the use of the isolated appendix as an intermittent catheterization route to empty a continent urinary reservoir. The procedure was popularized and numerous variations on the same principle were reported. Presence of histopathological abnormalities in the appendix may limit its suitability for reconstructive purposes. We studied the frequency of incidental histopathological abnormalities in appendixes removed electively in 122 urological patients during a radical pelvic operation. The implications for incorporation of the appendix in urinary tract reconstruction are evaluated. A total of 38 patients (31.1%) had notable histological abnormalities of the appendix: 35 had fibrous obliteration of the lumen, 2 had carcinoid tumor and 1 had a mucocele of the appendix. The rate of abnormal appendixes was significantly higher in elderly patients (more than 70 years old). Incidental pathology of the appendix is a frequent finding that may affect the immediate results and the late outcome of urinary tract reconstruction using the appendix. When such strategy of urinary tract reconstruction is considered, potential histopathological abnormalities should be anticipated. The patients should be informed and aware of possible unexpected changes in the preplanned procedure, while the surgeon must be familiar with these alternative reconstructive methods. PMID- 1613878 TI - Cytogenetic studies of carcinoma in situ of the bladder: prognostic implications. AB - Carcinoma in situ of the bladder has traditionally been considered a lethal disease by most urologists and as such it has been treated most frequently in an aggressive manner. Recent investigations have suggested that carcinoma in situ of the bladder may, in fact, be a complex of diseases that exists in at least 2 distinct disease forms, 1 aggressive and 1 relatively nonaggressive. We studied the cytogenetics of 17 patients diagnosed clinically and pathologically to have carcinoma in situ, and found a positive correlation of karyotype complexity (numerical and structural changes) with disease course. Superficial tumors with normal karyotypes remained superficial throughout the study and continued to exhibit a nonaggressive course, while patients whose tumors had an abnormal karyotype at diagnosis expressed a much more aggressive course that ultimately developed into invasive disease. Nonrandom chromosomal changes involving chromosomes 1, 5, 8 and 11 were observed in these tumors. Therefore, cytogenetic evaluation may prove to be an important guide in helping to determine an appropriate treatment course for patients with carcinoma in situ of the bladder. PMID- 1613879 TI - Deoxyribonucleic acid flow cytometry in invasive bladder carcinoma: a possible predictor for successful bladder preservation following transurethral surgery and chemotherapy-radiotherapy. AB - Tumor deoxyribonucleic acid (DNA) ploidy was evaluated as an objective parameter that may correlate better with the responsiveness of bladder cancer to chemotherapy plus radiotherapy than do clinical features or histopathological subtypes. A total of 40 patients with localized muscle-invading bladder cancer (clinical stages T2 to T4) underwent prospective treatment on a potential bladder preserving protocol. Tumors of 37 of the 40 patients were analyzed by DNA flow cytometry of multiple paraffin embedded specimens. Transurethral resection, neoadjuvant chemotherapy and 40 Gy. radiotherapy plus cisplatin were followed by urological reevaluation of the tumor (a complete response required a negative biopsy and a negative urine cytology study). A total of 7 noncomplete response patients underwent immediate radical cystectomy whereas the full bladder sparing treatment (radiotherapy to 64.80 Gy. plus cisplatin) was given to 23 complete response patients and 7 noncomplete response patients who were unsuited for surgery. Of the tumors 22 (59%) were purely aneuploid and 10 (27%) were purely diploid. Five tumors contained aneuploid and diploid patterns in different tumor specimens (partly diploid). Current status with a 30-month median followup in surviving patients includes an 82% overall survival rate in the aneuploid group versus 47% in the diploid/partly diploid group. Of all the patients 68% are free of invasive tumor: 82% in the aneuploid group versus 47% in the diploid/partly diploid group. By multivariate analysis pure aneuploidy was significantly (p = 0.05) correlated with freedom from invasive tumor in the bladder (either as persistence or as recurrence) and approached significance (p = 0.08) in correlation with overall patient survival. A longer observation time will be required to confirm this unexpectedly good outcome for patients with pure aneuploid tumors. We hypothesize that pretreatment DNA ploidy status may become a clinically useful prognostic factor in selecting patients for successful treatment with transurethral surgery and neoadjuvant chemotherapy plus radiotherapy. PMID- 1613880 TI - Combination cisplatin and dichloromethotrexate in patients with advanced bladder cancer. Phase 2. A Southwest Oncology Group study. AB - The combination of cisplatin and dichloromethotrexate is a pharmacologically rational strategy designed to avoid the nephrotoxicity associated with the systemic chemotherapy of bladder cancer. Of 97 patients with metastatic bladder cancer entered into this study 73 with good renal function received cisplatin and dichloromethotrexate, while 24 with impaired renal function received dichloromethotrexate alone. No responses were noted in the latter group. A 42% response rate (95% exact confidence interval 30.0 to 55.2%), including 9 patients (14%) who achieved a complete response, was observed in the combination group. The toxicity patterns in both groups of patients were consistent with the hypothesis that renal toxicity would be ameliorated with the use of the methotrexate analogue. However, the failure to achieve a higher overall response rate despite near maximum tolerated doses of dichloromethotrexate discourages future studies with this agent. New agents for metastatic bladder cancer should be tested as first line therapy. PMID- 1613881 TI - Modified vascularized pedicled scrotal flap for complex hypospadias. AB - Surgical correction of complex hypospadias defects is a problem. A 1-stage technique using a scrotal septum pedicled skin flap was used in 7 patients with inadequate preputial skin and scarred ventral penile skin unsuitable for satisfactory repair. The results were satisfactory in 5 patients. Distal urethral stricture developed in the remaining 2 patients and 1 of them had a subcoronal urethrocutaneous fistula. Minor hair growth was noted in 1 patient. The pedicled scrotal septum flap is recommended in selected cases of complex hypospadias, particularly when other methods fail. PMID- 1613882 TI - Congenital defect in sinusoidal smooth muscles: a cause of organic impotence. AB - We report 2 cases of primary impotence due to a congenital defect in the compliance of the sinusoidal spaces secondary to fibrosis and atrophy of the smooth muscles. Both patients were young adults at presentation. Diagnosis of this rare entity was achieved by penile Doppler ultrasound and cavernosometry/cavernosography of the cavernous bodies. Both patients underwent placement of a penile prosthesis, during which biopsy samples of the cavernous tissue were obtained, and diagnosis was confirmed by light and electron microscopy. PMID- 1613883 TI - The combined intracavernous injection and stimulation test: diagnostic accuracy. AB - A retrospective review was done of the results of the combined intracavernous injection and stimulation test, an office based functional test for impotence. In this procedure the quality of erection is assessed 15 minutes after injection of a vasoactive drug. In our series 90 patients did not achieve full rigidity and were instructed to perform genital self-stimulation for 5 minutes before reevaluation. Of the 90 patients 67 (74%) improved with stimulation and 23 (26%) showed no improvement. At 5 minutes after stimulation a decrease in the quality of the erection was found in 25 patients--a finding suggestive of venogenic impotence. When cavernosometry and cavernosography were performed 21 patients (84%) had moderate to severe venous leakage and 4 (16%) showed none. Self stimulation after diagnostic injection of intracavernous agents can improve patient response, and may better predict the potential success of a therapeutic self-injection program and the diagnosis of suspected venogenic impotence. PMID- 1613884 TI - Penile pharmacological duplex ultrasonography: a dose-effect study comparing papaverine, papaverine/phentolamine and prostaglandin E1. AB - Alternations of penile blood flow are believed to be the most frequent organic cause of erectile dysfunction. Penile duplex ultrasonography following intracavernous injection of a vasoactive agent is an accepted method for diagnosis of penile vascular dysfunction. To determine the diagnostic efficacy of commonly used vasoactive drugs we studied the hemodynamic effects of different dosages of papaverine, the combination of papaverine and phentolamine, and prostaglandin E1 in men with erectile dysfunction and men with normal erectile potency using color duplex ultrasonography. We concluded that 12.5 mg. papaverine and 10 micrograms. prostaglandin E1 are the drugs of choice to be used in conjunction with penile duplex ultrasonography because of optimal effects on cavernous arterial dilatation and low risk of prolonged erection. However, low dose papaverine or prostaglandin E1 has a limited value in evaluating veno occlusive function. PMID- 1613885 TI - Cancer metastatic to the penis: treatment with hyperthermia and radiation therapy and review of the literature. AB - Metastatic cancer to the penis is rare, its optimum treatment remains poorly defined and the outcome of patients with such metastases is poor. Hyperthermia in conjunction with radiation therapy has been shown to be an effective modality in the treatment of locally advanced or recurrent cancer and hyperthermia alone is under evaluation in treating benign disorders, such as hypertrophy of the prostate. Recently, 4 patients with symptomatic metastatic lesions to the penis (3 had primary prostatic cancer and 1 had rectal cancer) were treated with radiation therapy and hyperthermia. Treatment was well tolerated except for pain during hyperthermia, which limited the temperatures that could be obtained. All of the patients improved symptomatically, 1 achieved a complete response and 2 had partial responses. No significant complications were noted. Symptomatic control was maintained in all patients for the duration of their survival. This limited series suggests the possible role of local hyperthermia as an adjunct to radiation therapy in the treatment of metastases to the penis. PMID- 1613886 TI - Globotriaosyl ceramide glycolipid in seminoma: its clinicopathological importance in differentiation from testicular malignant lymphoma. AB - Glycolipids were biochemically extracted from 14 specimens of seminoma, 2 of testicular malignant lymphoma (both of which were difficult to differentiate from seminoma with a high mitotic index) and 4 of normal testicle. The pattern of their expression was compared. Marked accumulation of globotriaosyl ceramide was observed in seminoma but it was present in a small amount in testicular malignant lymphoma. Differentiation between seminoma and malignant lymphoma is sometimes difficult by histopathological findings but it is considered to be greatly facilitated by examination of the pattern of glycolipid expression. PMID- 1613887 TI - Prostatic abscess: diagnosis and treatment. AB - We present a series of 25 men with prostatic abscesses studied during an 11-year interval in whom prostatic fluctuation upon digital rectal examination was the most characteristic sign. Transrectal ultrasound was the most reliable method for diagnosis and transurethral drainage under antibiotic coverage was the ideal treatment for this disease. PMID- 1613888 TI - Correlation of prostate cancer nuclear deoxyribonucleic acid, size, shape and Gleason grade with pathological stage at radical prostatectomy. AB - Using image cytometry and a video planimetry unit, various deoxyribonucleic acid (DNA) measurements, nuclear size and shape factors, and Gleason grade were correlated with capsular penetration, seminal vesicle invasion and lymph node involvement in 113 radical prostatectomy specimens. Percentage of nondiploid cells was the best DNA measurement and standard deviation of nuclear area was the best size measurement correlating with capsular penetration. However, stepwise regression analysis demonstrated that Gleason grade was the only independent predictor of capsular penetration. The only parameter that independently predicted seminal vesicle invasion in a stepwise regression analysis was percentage of tetraploid cells. The mode of optical density was the best DNA measurement for predicting lymph node involvement, although stepwise regression analysis found that Gleason grade was the only independent predictor. DNA ploidy was not as predictive of pathological stage. In summary, DNA measurements and nuclear morphometry performed on smears offered relatively little additional prediction of pathological stage over that of Gleason grade. PMID- 1613889 TI - Early continence after radical prostatectomy. AB - A prospective evaluation of urinary continence in 60 consecutive patients undergoing radical prostatectomy with incorporation of the fascia posterior to the urethra into the vesicourethral anastomosis is described. With this technique complete continence without the need for pads has been achieved in 88% of the patients, with stress incontinence in 10% and total incontinence in 2%. Continence was achieved within 1 to 16 weeks, with 13% of the patients dry during week 1, 55% dry at 6 weeks and 83% dry at 3 months. The median interval to achieve continence was 5 weeks. Median age of the continent patients was significantly lower than that of incontinent patients (65 versus 69 years). Neither the number of neurovascular bundles resected nor the need to reconstruct the vesical neck affected the rate of continence. While the exact mechanism of continence after radical prostatectomy remains unknown, incorporation of the fascia posterior to the urethra into the vesicourethral anastomosis results in earlier continence and thereby lessens the morbidity of this procedure. PMID- 1613890 TI - A new procedure for biopsy of a solid renal mass: transurethral approach under fluoroscopic control. AB - Cystoscopically placed, fluoroscopically guided catheters were used to biopsy 3 solid renal tumors. One kidney had a renal cell carcinoma and 2 had transitional cell carcinoma invading the renal parenchyma, including 1 that had undergone various ureteroscopic biopsy techniques that failed to yield a diagnosis. The transurethral technique offers an alternative to open, laparoscopic or percutaneous biopsy in selected patients. PMID- 1613891 TI - Traffic death toll may be declining, but experts not ready to celebrate. PMID- 1613892 TI - Defining, counting traffic injuries no easy task as nation assesses toll from this violence. PMID- 1613893 TI - For three quarters of century, safety experts work to keep trains, vehicles from colliding. PMID- 1613894 TI - Simulator designed for advanced traffic research. PMID- 1613895 TI - Driving while under influence of alcohol remains major cause of traffic violence. PMID- 1613896 TI - Association dedicated to crash injury control. PMID- 1613897 TI - Seven years before centennial of first US traffic death, toll already has reached nearly 2.8 million. PMID- 1613898 TI - High-speed chases to high-powered squirters, moving traffic violations pose variety of threats. PMID- 1613899 TI - As nation grows older, traffic safety officials confront questions of who should drive. PMID- 1613901 TI - Highway fund threat is no easy ride for motorcycle helmet law opponents. PMID- 1613900 TI - Campaigns focus on helmets as safety experts warn bicycle riders to use--and preserve--heads. PMID- 1613902 TI - From the Centers for Disease Control. Trends in alcohol-related traffic fatalities, by sex--United States. PMID- 1613903 TI - From the Centers for Disease Control. Safety-belt and helmet use among high school students--United States, 1990. PMID- 1613904 TI - From the Centers for Disease Control. Table reporting alcohol involvement in fatal motor-vehicle crashes. PMID- 1613905 TI - From the Centers for Disease Control. Increased safety-belt use--United States, 1991. PMID- 1613906 TI - Contempo '92. PMID- 1613907 TI - Addiction medicine. PMID- 1613908 TI - Administrative medicine. PMID- 1613909 TI - Adolescent medicine. PMID- 1613910 TI - Anesthesiology. PMID- 1613911 TI - Cardiothoracic surgery. PMID- 1613912 TI - Cardiovascular disease. PMID- 1613913 TI - Critical care medicine. PMID- 1613914 TI - Economics. PMID- 1613915 TI - Emergency medicine. PMID- 1613916 TI - Endocrinology. PMID- 1613917 TI - Ethics. PMID- 1613918 TI - Family medicine. PMID- 1613919 TI - General internal medicine. PMID- 1613920 TI - Geriatric medicine. PMID- 1613921 TI - Government. PMID- 1613922 TI - Infectious diseases. PMID- 1613923 TI - Medical genetics. PMID- 1613924 TI - Medical toxicology. PMID- 1613925 TI - Neonatology. PMID- 1613926 TI - Neurological surgery. PMID- 1613927 TI - Neurology. PMID- 1613928 TI - Nutrition. PMID- 1613929 TI - Occupational and environmental medicine. PMID- 1613930 TI - Oncology. PMID- 1613931 TI - Ophthalmology. PMID- 1613932 TI - Otolaryngology-head and neck surgery. PMID- 1613933 TI - Pathology and laboratory medicine. PMID- 1613934 TI - Pediatrics. PMID- 1613935 TI - Preventive medicine and public health. PMID- 1613936 TI - Psychiatry. PMID- 1613937 TI - Pulmonary medicine. PMID- 1613938 TI - Quality in health care. PMID- 1613939 TI - Radiology. PMID- 1613941 TI - Surgery. PMID- 1613940 TI - Sports medicine. PMID- 1613942 TI - [Combined therapy with prostaglandin E1 ointment and lumbar sympathetic ganglion block on intractable skin ulcers accompanied by Burger's disease]. AB - For the 2 patients with intractable skin ulcers and pain accompanied by thromboangiitis obliterans (Burger's disease), we applied combined therapy with lumbar sympathetic block, continuous epidural block and prostaglandin E1 ointment. Prostaglandin E1 (PGE1) was prepared as a topical ointment by mixing with Plastibase (polyethylene resin, 5%, liquid paraffin, 95%) at a concentration of 10 micrograms.g-1. The ointment was kept in a refrigerator until use. Following debridement and washing of the surface of ulcers as required, the ointment was applied evenly onto the surrounding and over the surface of each ulcer 2 times daily after sterilization. With this therapy the ulcers were cured completely in 10 days after the start of treatment. No side effect was observed both locally and systemically. Although the combined therapy we used with prostaglandin E1 ointment was a noninvasive method, a remarkable shortening of the period of treatment was achieved. PMID- 1613943 TI - [A series of anesthesia for a child with Lowe's syndrome]. AB - A series of anesthesia for a child with Lowe's syndrome was reported. The boy underwent general anesthesia for 6 times for ophthalmic and dermatologic surgeries in approximately eight years since the age of only four months when the first anesthesia had been given. From the third to the fifth episodes of anesthesia, marked metabolic acidosis was noted, but at the first and second anesthesia, metabolic acidosis had not been recognized. Such acidosis was corrected each time by 7% NaHCO3 infusion at the early stage of anesthesia, and afterwards uneventful courses were seen. In the last anesthesia, acidosis was not found, though disturbance of renal functions were suspected because of abnormal urinary NAG and beta 2-microglobulin value in blood. Attention should be paid to possible anesthetic hazards in Lowe's syndrome patients such as metabolic acidosis due to the renal-tubular dysfunction, the risk of convulsion, glaucoma, the fragility of the bone structures, and so forth. PMID- 1613944 TI - [Anesthetic problems in patients with Forestier's disease]. AB - We have studied common problems associated with the anesthetic management of Forestier's disease in 8 patients undergoing neurosurgery. This disease is a systemic degenerative disorder and is characterized by osteo-spur formation at anterior spinal body. In two of eight patients the trachea was intubated with great difficulty even by well-trained anesthesiologist. Its cause could be found not only in limited cervical mobility but also in constrained epiglottic elevation, suggesting that Forestier's disease requires special anesthetic considerations. It is thus important to predict the possibility of difficult tracheal intubation on both physical examination and the preoperative X-ray photography. PMID- 1613945 TI - [Studies of emergency cardiopulmonary bypass (ECPB) for cardiopulmonary-cerebral resuscitation; (1) Introduction of a portable-percutaneous ECPB system]. AB - The authors have developed an ECPB system, which can be applied quickly, safely and easily under an emergency condition requiring cardiac massage and artificial ventilation. Fundamentally, the ECPB system consists of 3 parts; a portable ECPB apparatus, a pair of percutaneous cannulae and a short circuit connecting an oxygenator with the cannulae. The ECPB apparatus is assembled with commercially available components (i.e., a centrifugal pump, a battery pack, a temperature controller, a compact membrane oxygenator with a heat exchanger, etc) and they are placed on a mobile cart. The circuit is primed with 300 ml of lactated Ringer solution. The priming can be done within 15 minutes via a reservoir. It is also possible to keep the primed circuit to be ready for emergency use at least for a week. The cannulae are placed intravascularly through the femoral artery and vein by using the Seldinger's percutaneous method. In an emergency situation, the arterial and venous cannulations are carried out separately on the both inguinal regions to save time. The tip of the venous cannula is adjusted to be placed near the right atrium under fluoroscopy. Initiation of ECPB via the femoro-femoral V-A cannulae assures instant and stable supply of oxygenated blood to all of the vital organs. At the present time, nothing is more important than a quick supply of oxygenated blood to the brain to ameliorate the post-ischemic brain damage. PMID- 1613946 TI - [Effect of prostaglandin E1 on arterial ketone body ratio during gastrectomy]. AB - We evaluated the effect of prostaglandin E1 (PGE1) on arterial ketone body ratio (AKBR), which is a parameter to indicate the function of the liver cells, in the patients undergoing total or subtotal gastrectomy. Twenty patients were divided into two groups: continuous intravenous administration of PGE1 (0.02 micrograms.kg-1.min-1) was started from 30 minutes after the beginning of the operation in 10 patients, and the remainders did not receive PGE1. AKBR levels at 30 minutes after the beginning of the operation (during the resection of stomach) were significantly lower than those after the resection of stomach in both groups. A significant increase in AKBR caused by the administration of PGE1 was observed during the resection of the stomach in PGE1 group. However, almost no change was observed in AKBR during the resection of the stomach in control group. These findings suggest that the administration of PGE1 has a protective effect on liver which is due mainly to the increase in hepatic blood flow during the resection of stomach. PMID- 1613947 TI - [The effects of prostaglandin E1 infusion on the viscosity and pH of gastric fluid during general anesthesia]. AB - We studied the protective effect of prostaglandin E1 (PGE1)-induced hypotensive anesthesia on gastric mucosa in 30 elective surgical patients. Three groups, each composed of 10 patients, received PGE1, nitroglycerin or none during general anesthesia. Then we measured the viscosity and pH of gastric fluid continuously in each group. In the PGE1 group the viscosity and pH increased significantly and rapidly (P less than 0.05) as compared with the other groups. This suggests that PGE1 offers prophylactic effect against postoperative acute gastric mucosal lesion (AGML). PMID- 1613948 TI - [Usefulness of a disposable nasogastric tube with a pH sensor--comparison with a class pH electrode]. AB - We evaluated a disposable nasogastric tube with a pH sensor in comparison with an external glass pH electrode with aspiration of gastric contents, continuously. The mean pH value determined by pH sensor was 3.01, and 2.99 by glass pH electrode. There was a good correlation between the two methods (r = 0.91). The agreement between the two methods was especially good when pH less than 5.0. There was a wide scattering in the data when pH greater than 5.1. When the glass pH electrode data were above 5.1, the pH sensor tended to show lower pH values than glass pH electrode. PMID- 1613949 TI - [A new preoperative evaluation of platelet aggregation--Part II]. AB - With the new platelet function test which we reported in the first paper, the platelet aggregation was evaluated in 50 patients, and the comparison with the results of bleeding time was made in 20 cases. There was no statistical correlation between the bleeding time and the platelet aggregation. The bleeding time has been considered as an indicator of platelet function and is included in a preoperative check list. However, its result depends on the amount of platelets and the endothelial factor, and the reliability of bleeding time on platelet function is considered small, especially in patients medicated with antiplatelet drugs. For such patients, the platelet aggregation test is essential. The present study demonstrated that the patient belonging to grade-1 were resistant to hemostasis during the operation. Taking into the surgical and anesthetic depression on the platelet function into consideration, the patients below grade 2 are risky for the surgery. PMID- 1613950 TI - [Evaluation of efficacy of maximum surgical blood order schedule (MSBOS) in the operating room]. AB - We evaluated efficacy of maximum surgical blood order schedule (MSBOS) using analysis of cross-match to transfusion ratio (C/T ratio) during 1 year after applying MSBOS to operations in our operating room. The MSBOS used was based on our trial reported in 1990. Compared with preoperative prepared blood units before application of MSBOS, C/T ratio decreased from 4.76 to 3.44, and cross matched blood units decrease from 476 units to 344 units (about 72%) per 100 packs of transfused blood. We conclude that application of MSBOS is effective and useful for saving preoperative prepared blood. Analysis with C/T ratio was very useful to recognize the present status of preparations of blood for surgery preoperatively. MSBOS should be re-evaluated regularly because of changes of operative environment such as surgeon, operative method, preoperative condition of patients, and so on. PMID- 1613951 TI - [Serum catecholamine concentrations and hemodynamics during operations on 23 children with neuroblastoma]. AB - The purpose of the present report is to reveal the relation between hemodynamic changes and serum catecholamine concentrations during operation of 23 neuroblastoma patients. The patients were aged from 6 months to 7 years (mean 1.2 year), and 20 patients (86%) were under 1 year of age. All the patients were in early stage of tumor development because they were diagnosed as neuroblastoma mainly by mass screening test for VMA and HVA in urine utilizing HPLC. This urinary mass screening test for infants is performed routinely in Japan. Operative manipulation of tumor provoked the significant elevation of blood pressure, and the increasing tendency of heart rate and rectal temperature. The mean concentrations of three kinds of serum catecholamine, epinephrine, norepinephrine and dopamine, were all very high during manipulation of tumor. Especially, the norepinephrine concentration was 90.2 times higher than the preoperative value. The children who showed high blood pressure, over 70% of the control level, showed high urinary VMA and VMA/HVA ratio preoperatively and a high norepinephrine secretion during operation. We conclude that for the anesthetic management of neuroblastoma, it is necessary to control the elevation of blood pressure even in small children, especially in the patients who have showed high values of urinary VMA and VMA/HVA ratio preoperatively. PMID- 1613952 TI - [Measurement of functional residual capacity by sulfur hexafluoride washout]. AB - An open circuit tracer gas washout method for measurement of functional residual capacity (FRC) during mechanical ventilation is described and tested. The system employed a piezo-valve for dispensing sulfur hexafluoride (SF6) gas, a fast response infrared SF6 analyzer, Servo 900-C ventilator and a computer. The piezo valve unit delivers SF6 into the airway in proportion to instantaneous inspiratory flow so that inspiratory SF6 concentration was held constant regardless of the inspiratory flow pattern. The washin concentration was approximately 0.6% which was so low that the supply of other gases was hardly influenced. The amount of SF6 at the end of a washin was calculated during washout by signals of expired SF6 concentration and expired flow. The results obtained in model lungs were accurate and reproducible; mean difference (limits of agreements) was 14 +/- 48ml (M +/- 2SD) in the range between 0.5 and 3.0 liters. Comparison with helium dilution methods in 24 healthy subjects gave a regression equation: y = 0.98x + 56, r = 0.98. The mean difference of the values between the two methods was 21 +/- 142 ml (M +/- 2SD). The authors conclude that the system is quite useful in determining FRC of the patients under mechanical ventilation. PMID- 1613953 TI - [The influence of lung volume and body position on pulmonary blood flow under hypoxic exposure]. AB - We examined the changes in the electromagnetically measured left lower lobe blood flow (QLLL) when the left lower lobe (LLL) was exposed to alveolar hypoxia selectively under two different positions (supine and right lateral position in 18 dogs. QLLL/CO, Qs/Qt and other cardiopulmonary parameters were obtained during the following experimental sequence; 1) the whole lung ventilated with 100% O2 (control), 2) LLL collapsed and the remainder ventilated with 100% O2, 3) N2 expansion of LLL (N2 CPAP) and the remainder ventilated with 100% O2, 4) O2 expansion of LLL (O2 CPAP) and the remainder ventilated with 100% O2, and 5) The whole lung ventilated with 100% O2. In the supine position group (n = 9), both selective collapse and N2 CPAP of LLL caused QLLL/CO to decrease significantly (P less than 0.02) from control values (14.9 +/- 1.7%) to 10.6 +/- 0.9% and 11.9 +/- 1.6%, respectively. But there was no difference in QLLL/CO between collapse and N2 CPAP of LLL. In the right lateral position group (n = 9), hypoxic exposure of LLL caused no decrease in QLLL/CO from control values. But QLLL/CO during N2 CPAP (8.5 +/- 1.1%) decreased significantly than that during collapse (10.8 +/- 1.5%) (P less than 0.02). Qs/Qt during N2 CPAP (15.6 +/- 1.4%) also decreased significantly (P less than 0.05) from that during collapse (18.5 +/- 2.2%). We conclude that the difference of the changes in QLLL/CO under hypoxic exposure between supine and right lateral position was caused by hydrostatic pressure which influenced more during lateral position than during supine position. PMID- 1613954 TI - [The effect of age and gender on the effect of midazolam as intramuscular premedicant]. AB - This study was designed to quantify the appropriate dose of midazolam relating to age and gender for intramuscular premedication. Three hundred and eighty-six consecutive patients (15-83 years) received midazolam (2.5-5.5 mg) with atropine 30 minutes prior to surgery. The perioperative effects of midazolam on arterial pressure as well as heart rate, SpO2 and amnesic effects of regional anesthesia were evaluated in patients divided to 10-year age intervals. Reduction of arterial pressure correlated with preanesthetic values (r = 0.515, P less than 0.01). Especially in those over 60 years, we observed significant reductions. Besides, compared with the males, the reduction was smaller in females. On the arrival at the operating room, this reduction recovered slightly, but preanesthetic hypertension was still attenuated effectively. After age 70, the SpO2 was lower, while the amnesic effect during regional anesthesia was significantly prominent. Amnesic effect correlated more with the dose than the dosage determined by body weight. Younger female patients required larger dosage determined by body weight than the corresponding male. As age increases, dose adjustment should be made mostly on the basis of age, and its adjustment on the basis of body weight should be made with great caution. In this study, we determined the appropriate dose of midazolam, 5 mg for those males younger than 60 years and females below 50 years, and 3-3.5 mg for those older than 80 years. PMID- 1613955 TI - [An experimental study on the appropriate proportion of dopamine and dobutamine for mixed infusion to treat cardiopulmonary dysfunction]. AB - This study was aimed to investigate appropriate proportion for combined use of dopamine (DA) and dobutamine (DB) to treat cardiopulmonary dysfunction. The total dose of 10 micrograms.kg-1.min-1 with several different proportions in steps of 2 micrograms.kg-1.min-1 of DA and DB was administered to mongrel dogs with intact lung and with cardiopulmonary dysfunction caused by lung edema induced by oleic acid instillation. The hemodynamic variables during and after the infusion with the combined dosages of both agents were compared with that of baseline values. In dogs with intact lung, cardiac index (CI) increased significantly in all proportions of both agents. The levels of CI tend to increase prominently when the proportion of DB in the mixture was increased. Heart rates showed a tendency to increase with higher proportion of DB. Increasing proportions of DA caused a more increase of arterial pressure than by increasing that of DB. In dogs with pulmonary edema, these hemodynamic characteristics with the proportional changes of both drugs were demonstrated more significantly than in normal dogs. From these results, it was concluded that the appropriate combined preparation of both agents to increase CI without extreme tachycardia in dogs with cardiopulmonary dysfunction was the mixed solution of DA 2-4 micrograms.kg-1.min-1 and DB 6-8 micrograms.kg-1.min-1. PMID- 1613956 TI - [Serum and urinary inorganic fluoride levels after prolonged inhalation of sevoflurane in man]. AB - The serum and urinary concentrations of inorganic fluoride were measured before and after sevoflurane anesthesia in ten patients without renal disease, who underwent surgeries lasting for 13.4 +/- 0.9 hours. The mean concentration of serum inorganic fluoride reached a maximal value of 42.5 +/- SE mumol.liter-1 at the end of anesthesia. However, the serum inorganic fluoride concentration increased over 50 mumol.liter-1 which is called "nephrotoxic threshold" in five of ten patients. A positive correlation was found between serum inorganic fluoride concentration and anesthetic dose. The largest urinary excretion of inorganic fluoride was 1804 +/- SE mumol.day-1 in the first postoperative day and the excretion decreased rapidly thereafter. We conclude that while nephrotoxicity was not demonstrated from biochemical data in this study, prolonged inhalation of sevoflurane (13.4 +/- 0.9 hours) increases serum inorganic fluoride concentration during and after the inhalation which may influence renal function. PMID- 1613957 TI - [Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine. 14. Effect on epidural pressure]. AB - We studied effect of total intravenous anesthesia using ketamine, fentanyl and droperidol (DFK) on epidural pressure as an index for cerebrospinal fluid pressure in six surgical patients who underwent gastrectomy. The epidural catheter was inserted on the previous day. The epidural puncture was made at Th7 12 and the tip of the catheter was located 5 cm cephalad. The epidural pressure was measured before, just after and 30 minutes after the induction. The induction dose of fentanyl was 5 micrograms.kg-1 and that of ketamine was 1 mg.kg-1. The epidural pressure at the induction decreased in significantly by 19% as compared with that before the induction. The result suggested that DFK would not increase cerebrospinal fluid pressure when the doses of ketamine and fentanyl were changed. PMID- 1613958 TI - [Clinical study on total intravenous anesthesia with droperidol, pentazocine and ketamine]. AB - Fifty patients underwent various surgical procedures including abdominal, orthopedic, plastic and gynecological operations under total intravenous anesthesia with ketamine, pentazocine and droperidol. Neither nitrous oxide, inhaled anesthetics nor narcotics such as fentanyl were administered to the patients. Intraoperative muscle relaxation was achieved with vecuronium and the patients were ventilated manually throughout the surgical procedures. Thirty percent of the patients developed hypertension and tachycardia, but they were easily overcome with administration of calcium ion channel blocker. Their peripheral circulation as well as urine output was well maintained. No adverse effects on the liver and kidney were observed post-operatively. Their post operative sedation and analgesia were evaluated excellent. A few patients had strange dream as if they might have missed their way into the "pink" tunnel. The data above described suggest that this anesthetic method would deserve further detailed clinical study. PMID- 1613959 TI - [Valve injury: a new complication of internal jugular vein cannulation]. AB - Although internal jugular vein cannulation is performed commonly, most physicians are not aware of existence of the internal jugular venous valve. This is the only valve between the right atrium of the heart and the brain, and it has an important role of preventing retrograde blood flow and increased back pressure to the brain. In this study, anatomic appearance of human internal jugular valves is described, and the competence of these valves is assessed. We examined also a safe approach to percutaneous cannulation of the internal jugular vein to avoid this complication. In the cadaveric subjects, the internal jugular vein with its valve was removed at the time of autopsy. In the living subjects, to examine the movement of this valve, endoscopic visualization utilizing the superfine fiberscope, and ultrasound techniques were applied. Next, to detect the competence of the jugular venous valve, transvalvular pressure gradients were measured. Nineteen internal jugular valves were obtained from 20 cadaveric subjects. These valves were situated directly above the termination of the internal jugular vein into the inferior bulb. The opening and closing of the valve were easily visualized with both superfine fiberscope and real-time ultrasound technique. Patients with competent valves showed transvalvular pressure gradients of 50-100 mmHg during cough-induced high intrathoracic pressure. Internal jugular venous valve is located 0.5-2.0 cm above the union of the subclavian and internal jugular veins, and the central approach performed at the summit of the cervical triangle has been shown to have a risk of injuring the internal jugular venous valve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613960 TI - [Usefulness of 0.02 percent epinephrine solution to widen the nasal cavity]. AB - There are many reports describing how to use epinephrine solution before nasal intubation, but there are few reports showing how much of the nasal cavity is widened by using epinephrine solution. The purpose of this study is to examine the usefulness of epinephrine solution to widen the nasal cavity before nasal intubation by measuring the decrease of the nasal concha. Twenty patients who were scheduled for nasal intubation were divided into two groups: 0.02 percent (1:5000) epinephrine solution (0.02 group, n = 10). 0.033 percent (1:3000) epinephrine solution (0.033 group, n = 10). The solutions were instilled on long cotton-tipped applicators that were slowly inserted until they reached posterior wall of the nasopharynx. We examined the area of the inferior nasal concha on X-P before and after inserting applicators in two groups. The area of the inferior nasal concha on X-P decreased 25 percent and 27 percent after using epinephrine solution in 0.02 group and 0.033 group, respectively and the decreases of the area were significant. But there was no significant difference between two groups. We conclude that 0.02 percent epinephrine solution is useful and adequate to widen the nasal cavity before nasal intubation. PMID- 1613961 TI - [Troubled endotracheal intubation: an adult case of anomalous tracheal bronchus]. AB - We experienced troubled endotracheal intubation in an adult patient with asymptomatic tracheal bronchus. The breath sounds of the right upper lobe were found to be absent right after the placement of a tracheal tube. An anomalous tracheal bronchus (displaced right upper lobar bronchus originating about 1 cm above carina) was found by fiberoptic bronchoscopy. The length of trachea of the patient was about 6 cm shorter than that of the normal value of adult male, which significantly reduced the safe range of positioning a tracheal tube. In a patient with this anomaly, who is otherwise healthy, a placement of a tracheal tube may cause pulmonary complications. Thus, as a diminished breath sound is found to be located at the upper right lobe after endotracheal intubation, we have to think of tracheal bronchus as one of the possible causes. PMID- 1613962 TI - [A case report of a 63-year-old patient with malignant hyperthermia]. AB - We have experienced a case of fulminant malignant hyperthermia who was a 63-year old female weighing 44 kg. There was no particular past history nor family history. She underwent right mastoidectomy because of chronic otitis media. Her preoperative physical status was ASA I. She was premedicated with diazepam 10 mg and loxatigine 75 mg P.O. The induction was done with thiamylal 200 mg IV and fentanyl 0.1 mg IV followed by vecuronium 6 mg IV for endotracheal intubation. Intubation was easy and uneventful. Anesthesia was maintained with nitrous oxide 3 l.min-1, oxygen 3 l.min-1 and enflurane 2.0%. Seventy min after the induction of anesthesia, arterial blood gas analysis showed severe respiratory acidosis (PCO2: 63.2 mmHg, pH: 7.27) and it was improved with manual hyperventilation at that time. Pulse rate increased from 80 to 115 b.p.m. 20 minutes later. Then, the patient was ventilated with 100% oxygen, and anesthetic circuits and machine were exchanged for new units. Surgery was postponed. Muscle stiffness of upper extremities was observed and her temperature increased to a maximum of 38.9 degrees C. Surface cooling was started and dantrolene sodium 60 mg and furosemide 20 mg were given intravenously. The patient was transferred to the intensive care unit, and clinical signs improved gradually within one hour. Serum enzymes; CPK, LDH, GOT and GPT increased on the first postoperative day. On the 11 th postoperative day skeletal muscle biopsy was done under local anesthesia with 1% procaine and Ca-induced Ca-release rate test revealed positive for enflurane. This is the oldest patient of malignant hyperthermia reported in Japan. PMID- 1613963 TI - [The catecholamine concentrations of collected autologous blood during adrenalectomy for pheochromocytoma]. AB - We have studied the concentrations of catecholamines in collected autologous blood. The measured levels of the blood samples from Cell-stat collecting chamber were epinephrine 4.74 ng.ml-1 and norepinephrine 2.39 ng.ml-1. First wash of collected blood with 700 ml of saline diluted the catecholamine concentrations to epinephrine 3.13 ng.ml-1 and norepinephrine 1.6 ng.ml-1. The concentrations of catecholamines after second wash were epinephrine 2.19 ng.ml-1 and norepinephrine 1.11 ng.ml-1. These values were three to twenty folds of normal ranges even after the second wash, and still the same levels as intraoperative plasma catecholamine (the measured values; epinephrine 0.81-2.81 ng.ml-1 and norepinephrine 0.96-3.15 ng.ml-1). Since platelets actively concentrate catecholamines during their life span, the destruction of platelets by suction or centrifugation may probably play the most important role in the elevation of catecholamine concentrations in the collected autologous blood. We concluded that intraoperative autotransfusion in the resection of pheochromocytoma is likely to result in the elevation of systemic blood pressure by catecholamines of the transfused blood. PMID- 1613964 TI - [Hemodilutional and blood salvaging autotransfusions in a case of aplastic anemia]. AB - A 28-year-old female, weighing 46 kg, 155 cm in height, with aplastic anemia underwent implantation of iliac bone to the head of the femur. A combined technique of hemodilution and intraoperative blood salvaging was applied to supplement the blood loss during the operation. Intraoperative monitoring included continuous arterial pressure, heart rate, electrocardiograph, SVO2, bleeding time, prothrombin time (PT), activated thromboplastin time (APTT), and thromboelastography. A total of 900 ml of blood was drawn and the same volume of 5% albumin solution was infused over half an hour before the beginning of the surgery. During the operation, 2100 ml of blood was lost, and 1260 ml of autologous blood, 400 ml of homogeneous red blood cells and 5 units of fresh platelet were infused. The values of PT, APTT, bleeding time were within normal ranges after the surgery. Only 3 units of fresh platelet was infused in 2 weeks after the surgery. It was suggested that hemodilution and salvaging autotransfusion is safely performed and beneficial to minimize homogeneous blood transfusion even in a case of aplastic anemia. PMID- 1613965 TI - [Therapeutic evaluation of imipenem/cilastatin sodium for bacterial infections in patients with hematological diseases]. AB - 1. To evaluate the efficacy and tolerance of imipenem/cilastatin sodium (IPM/CS) in severe infections associated with hematopoietic disorders, IPM/CS was administered to a total of 105 patients. 2. Out of 96 patients evaluable for efficacy, clinical responses were excellent in 23 patients, good in 30, fair in 15, poor in 19 and unknown in 9, and the overall response rate was 60.9%. 3. The most common underlying hematopoietic disease was acute non-lymphocytic leukemia and the most common infections were sepsis and suspected sepsis. 4. Daily dose, severity of infection and neutrophil count had effects on the clinical response. 5. The overall eradication rate of bacteria was 83.7%. 6. Side effects were observed in 10 patients (9.5%) and abnormal laboratory test results in 12 (11.4%). From the above findings, we have concluded that IPM/CS is very useful for the treatment of severe infections in compromised patients with hematopoietic diseases. PMID- 1613966 TI - [Free concentration and protein binding of ceftriaxone]. AB - Ceftriaxone (CTRX) was administered in dose of 1 g 30 minutes intravenous drip infusion to 5 healthy volunteers. Cefpiramide (CPM) and cefotetan (CTT) were administered as control antibiotics. The serum concentrations of total and free drugs, using ultrafiltration, were assayed by bioassay and HPLC. Protein binding rates and pharmacokinetic parameters were calculated. Free concentration of antibiotics were following orders in each sampling time: CTRX greater than CTT greater than CPM. Mean free concentrations of CTRX at 0 hour and at 8 hours after intravenous drip infusion was more than 20 micrograms/ml and more than 2 micrograms/ml. Even at 24 hours after intravenous drip infusion free concentrations of CTRX were detectable. Mean half life in beta phase by HPLC was following orders: CTRX (7.5 hours) greater than CPM (5.4 hours) greater than CTT (4.7 hours). Mean protein binding rates were following orders: CPM (98%) greater than CTT (94%) greater than CTRX (92%). CONCLUSIONS: Characteristic of CTRX is high free drug concentration and long half life. PMID- 1613967 TI - [A study on in vitro antibacterial activity and clinical usefulness in respiratory tract infections of panipenem/betamipron, a newly synthesized carbapenem antibiotic]. AB - Panipenem/betamipron (PAPM/BP) is a combination drug of PAPM, a new parenteral carbapenem antibiotic and BP, an amino acid derivative at a weight ratio of 1:1. Its in vitro antibacterial activities against clinically isolated respiratory pathogenic bacteria were determined. It was superior to imipenem (IPM) in the in vitro antibacterial activities against Haemophilus influenzae, Haemophilus parainfluenzae, Branhamella catarrhalis, Staphylococcus aureus including MRSA, Klebsiella pneumoniae, Serratia marcescens and Escherichia coli. PAPM had antibacterial activities almost equal to those of IPM against Streptococcus pneumoniae and Enterococcus spp. Against Pseudomonas aeruginosa, however, its antibacterial activity was about 1/4 that of IPM. The clinical usefulness of PAPM/BP was studied by dissolving it in a solution containing lactate and administering the solution by intravenous drip infusion to 12 cases of respiratory tract infections. Out of 11 cases with respiratory tract infections excluding cytomegalovirus pneumonia, the efficacy rate was 90.9%, with 4 cases of excellent and 6 cases of good responses. In terms of its bacteriological efficacies, eradication of pathogenic bacteria including super-infection were observed in 2 out of 4 strains, but 2 strains of P. aeruginosa remained unchanged. Six strains appeared as superinfected bacteria during and after administration of this preparation substituting original pathogens. Side-effects were not observed in the 12 cases, and in laboratory tests, slight transient increases of S-GOT and S-GPT were found in 1 case. In conclusion, PAPM/BP is a very useful parenteral antibiotic against respiratory tract infections and can be one of the drugs of the first choice. PMID- 1613968 TI - [Investigation of panipenem/betamipron levels in sera and various tissues in patients of orthopedic surgery]. AB - Panipenem/betamipron (PAPM/BP), a new parenteral carbapenem antibiotic, was investigated with regard to their levels in sera and various tissues collected from patients under orthopedic surgery. The subjects were 17 patients, complaining low back pain and hospitalized for surgical operations. PAPM/BP was administered by intravenous drip infusion for 30 minutes of a dose of 500 mg/500 mg. Serum and cerebrospinal fluid (CSF) specimens were taken from 8 patients at 15-70 minutes after administration and assayed for PAPM and BP levels. Serum, bone, and joint capsule samples where taken from the other 9 cases at 25-127 minutes after administration and assayed. PAPM levels in CSF were considerably lower than those in serum. They were 23.74-1.11 micrograms/ml in sera, 0.31-0.05 micrograms/ml in CSF's during 15 to 70 minutes after administration. PAPM levels were 27.85-2.97 micrograms/ml in sera, 2.54-0.20 micrograms/g in bones, 5.63 and 1.67 micrograms/g in joint capsules during 25 to 127 minutes after administration. BP levels in sera and various tissues were low compared to those of PAPM. These results showed that PAPM was detected at higher levels than 0.2 microgram/g in various tissues, except CSF during 20 to 120 minutes after drip infusion of PAPM/BP 500 mg/500 mg for 30 minutes. PMID- 1613969 TI - [A clinical study on panipenem/betamipron in chronic respiratory tract infections]. AB - Panipenem/betamipron (CS-976, PAPM/BP), a new carbapenem antibiotic, was administered a single dose of 500 mg or 750 mg via intravenous drip infusion twice a day for treatment of chronic respiratory infection to study its clinical efficacy, bacteriological efficacy and safety. Twenty nine cases were studied for the efficacy evaluation. Only the safety evaluation was made in 6 cases which were judged to be unsuitable, because in some of them pneumonia and other diseases were not specified as the subject diseases, of serious illness in some the conditions were too serious, and in the other cases the duration of administration was insufficient since administration had to be discontinued due to side-effects. The duration of administration was 6 to 18 days with 1 g divided into 2 doses daily or 4 to 15 days with 1.5 g in 2 divided doses daily. When clinical efficacies were classified according to different diseases, this preparation was effective in 11 cases and slightly effective in 1 case of 12 cases of chronic bronchitis with an efficacy rate of 91.7%. It was effective in 10 cases, slightly effective in 1 case and ineffective in 1 case of 12 cases of bronchiectasis with an efficacy rate of 83.3%. It was slightly effective in 2 and ineffective in 1 out of 3 cases of diffuse panbronchiolitis, and was effective in 2 cases of pulmonary emphysema with infections. PAPM/BP was given at a dose level of 1 g in 2 divided doses daily to 17 cases and that of 1.5 g in 2 divided doses daily to 10 cases. For the remaining 2 cases, changes in the dose level were made in middle course of treatment. The efficacy rate in the 1 g regimen was 76.5% and that with the 1.5 g regimen was 90%. The overall results in the 29 cases included 23 effective, 4 slightly effective and 2 ineffective cases, thus the overall efficacy rate was 79.3%. As pathogens, 11 species including 24 strains were isolated and identified from 19 cases. They were Gram-positive cocci including 2 strains each of Staphylococcus aureus and Streptococcus pneumoniae, 1 strain each of Staphylococcus epidermidis, Streptococcus sanguis, and Streptococcus viridans and a strain of Streptococcus spp., and Gram-negative rods including 9 strains of Pseudomonas aeruginosa, 4 strains of Haemophilus influenzae and 1 strain each of Klebsiella pneumoniae, Enterobacter cloacae and Pseudomonas spp.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1613970 TI - [Clinical evaluation of panipenem/betamipron in severe infections complicating hematological disorders]. AB - Forty-three patients with severe infections which were complicating hematological disorders were treated with panipenem/betamipron, and the efficacy and the safety of the drug were evaluated. The results obtained are summarized below. 1. Out of 40 patients in whom efficacies are evaluable, the clinical responses were excellent in 17 patients, good in 4, fair in 7 and poor in 12, and the total clinical efficacy rate was 52.5%. 2. The efficacy rate in 7 patients who had failed to respond to prior treatment with other antibiotics was 57.1%. Thus, no significant difference was observed in efficacy rates between the patients who had failed to respond to prior treatment with other antibiotics and the patients who received no preceding antibiotics therapy. 3. Out of the 43 patients in whom the safety was evaluable, no side effects nor abnormal laboratory findings were found. PMID- 1613971 TI - [Clinical study of panipenem/betamipron for burn infections in the domain of plastic and reconstructive surgery]. AB - The effectiveness and the safety of panipenem/betamipron, new antibiotics of the carbapenems for burn infections, were studied and the following results were obtained: 1. The preparation, 0.5 g/0.5 g, was administered by intravenous drip infusion twice a day to 11 cases of patients with burn infections. In 10 cases for which clinical effects were evaluable, results were rated as "excellent" in 2 cases, "good" in 2 cases and "fair" in 6 cases, with an efficacy rate of 40%. 2. Penetration to the affected tissue was studied in 2 cases. The tissue level of panipenem was 0.20 micrograms/g immediately after the end of drip infusion and 6.86 micrograms/g 60 minutes thereafter. 3. As for the safety, a slight increase in GOT, GPT and Al-P was noted in 1 case; a slight increase in GPT, NAG and beta 2MG was found in 1 case; and a slight increase in GOT, GPT, Al-P and LAP was noted in 1 case, as abnormal variations in laboratory test results. PMID- 1613972 TI - [Studies on the efficacy and safety of panipenem/betamipron in infections in surgical domain and the safety when mixed with lactate containing infusion]. AB - Studies were done on the effectiveness and safety of panipenem/betamipron, a new carbapenem antibiotic, in infections in the surgical domain and its safety when dissolved in infusions containing lactate. The obtained results are summarized as follows. The preparation, 0.5 g/0.5 g or 1.0 g/1.0 g, was administered by intravenous drip infusion 2 to 3 times a day to 31 cases of patients with infections in the surgical domain. A physiological saline solution was used as the solvent in 21 cases (group A) of them and Solita T3, an infusion containing lactate, was used as the solvent in the 10 remaining cases (group B). As for its clinical effects, results were rated as "excellent" in 20, "good" in 7, "fair" in 3 and "no response" in 1 out of the 31 cases, and the efficacy rate was 87.1%. Regarding its bacteriological effects, results were rated as "disappeared" in 22, "decreased" in 2, "unchanged" in 1 and "unknown" in 1 out of 26 cases from which bacteria were isolated, hence the bacteria-clearance rate was 88.0%. As for side effects, skin rash was seen in 1 case and slight increases of GOT and GPT were noted as abnormal changes in laboratory data in 2 cases. These side effects were all observed among the cases in group A but not at all in group B where a lactate containing infusion was used as the solvent. PMID- 1613973 TI - [A multicenter study on panipenem/betamipron in dermatology]. AB - Panipenem/betamipron (PAPM/BP), a new carbapenem, was studied in dermatology. PAPM/BP was used clinically in the treatment of skin and skin structure infections in a multicenter trial. Fifty three patients were enrolled in the trial. Clinical evaluations were made in 50 patients. Most patients received intravenous infusion of PAPM/BP in a dose of 500 mg twice daily. Other dosages were used in some patients. The overall clinical efficacy rate was 78%. When 15 cases of secondary infections were excluded, the rate was 85.7%. Adverse responses were nausea and/or vomiting in 3 patients, redness with itching in 1 patient, headache or head heaviness in 2 patients and diarrhea in 1 patient. The patient with redness and itching had also nausea and vomiting. This occurred 1 hour after the start of the first infusion of this drug. After the discontinuation of the treatment the symptoms went away on the next day. Abnormalities in laboratory test results were observed in 7 out of 53 patients. One patient with liver cirrhosis and hepatocellular carcinoma developed anemia (RBC 372 x 10(4)/mm3----275 x 10(4)/mm3, Hb 11.9 g/dl----8.8 g/dl, 35.1%--- 26.0%). Other abnormalities were all mild. Penetration of the drug into skin tissues after intravenous infusion of 500 mg of this drug in skin surgery patients was studied. Skin/serum concentration ratios ranged from 0.20 to 0.97. Skin concentrations were higher than the concentration of PAPM inhibiting 80% of clinical isolates over a period of 6 hours. In rats, skin concentrations were much lower than serum concentrations probably due to the difference in in vivo metabolism of PAPM. A few resistant strains of Staphylococcus aureus against PAPM and imipenem (IPM) were isolated. However, PAPM and IPM showed good antibacterial activities compared to other drugs tested. In conclusion, PAPM/BP is considered to be a useful drug in the treatment of skin and skin structure infections. PMID- 1613974 TI - [Shape change in human megakaryoblastic leukemia cells, MEG-01]. AB - We investigated the intracellular processes of the shape change in the human megakaryoblastic leukemia cell, MEG-01, by platelet agonists. Thrombin induced the formation of many pseudopods. This shape change was also induced by TPA and A23187, but not by ADP, collagen, or epinephrine. Electron microscopy and FITC labeled phalloidin staining revealed thick submembranous microfilament bundles in the pseudopods of the shape-changed cells induced by thrombin. Shape change was inhibited by cytochalasin B. Protein kinase C (RKC) inhibitor, H-7, markedly inhibited thrombin-induced shape change, while the myosin light chain kinase (MLCK) inhibitor, ML-9 did not. These results suggest that thrombin-induced reorganization of microfilaments and shape change of MEG-01 cells are mediated by PKC but not by MLCK. PMID- 1613975 TI - [Role of GTP-binding proteins in phospholipid metabolism in human platelets]. AB - Phosphoinositide-specific phospholipase C (PLC) catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DG), which act as second messengers. Substantial evidence has strongly suggested that a putative G-protein (s), Gp, regulates PLC activity in human platelets. Recently, the molecular mechanism of PLC activity regulation was clarified as to two types of enzymes, PLC-gamma and PLC-beta. In this chapter, the regulatory mechanisms of the PLCs via a Gp or tyrosine kinase is summarized, and the involvement of some G-protein in the regulation of other phospholipases, phosphatidylcholine-specific PLC, phospholipase A2 and phospholipase D, is also discussed. PMID- 1613976 TI - [Small GTP-binding protein and platelet function]. AB - In platelets, nearly ten small GTP-binding proteins (G proteins) are identified. Among these small G proteins, smg p21 is the most abundant. The C terminus of smg p21 is processed by three post-translational modifications: geranylgeranylation, removal of three amino acids and carboxyl methylation. There are two regulatory proteins for smg p21, smg p21 GTPase activating protein (GAP) and smg GDP dissociation stimulator (GDS). Moreover, smg p21 is phosphorylated by A-Kinase and this phosphorylation stimulates the action of smg GDS. C-Kinase and Ca2+ induce platelet activation, while A-Kinase antagonizes this activation. Since smg p21 is the substrate of A-Kinase, it is possible that smg p21 mediates the A Kinase action and inhibits the platelet function, such as aggregation and secretion. The mode of action of and the possible function of smg p21 in platelets are discussed. PMID- 1613977 TI - [Platelet membrane glycoproteins and the molecular mechanisms of hereditary platelet dysfunction]. AB - Glycoproteins, present on the outer surface of platelets, function in the aggregating and releasing reactions of these cells. Some of the hereditary diseases of platelet dysfunction, such as, thrombasthenia and Bernard-Soulier syndrome, have been shown to result from defects in some of these glycoproteins. Recent advances in molecular biology have enabled us to analyze the genes which encode the defective glycoproteins in these patients. The information from these studies also helps us to understand in detail the function of the glycoproteins. At present, the major glycoproteins, GP II b/IIIa and GP I b/IX, have been studied extensively and we know the details of the mechanisms through which they function. However, as to the minor glycoproteins, GP I a/II a, GP IV and GP VI, details remain to be elucidated. PMID- 1613978 TI - [Effect of protein kinase C activation on platelet Na+/H+ exchanger]. AB - Protein kinase C activation in human platelets has a modulatory role in maintaining intracellular pH (pHi), by adjusting pHi at a particular value (pH 7.22). Changes in pHi induced by protein kinase C appeared to depend upon differences between H+ efflux catalyzed by Na+/H+ exchanger and H+ production. The pHi recovery after acid loading was significantly facilitated by protein kinase C activation. Analysis of the rate constant for pHi recovery suggested that the turnover rate or the apparent affinity of the Na+/H+ exchanger for H+ was increased. Protein kinase C also decreased the Km value of the Na+/H+ exchanger for extracellular Na+. It is suggested that the role of protein kinase C in platelet pHi regulation is dual, adjusting the pHi value at a certain set point, on the one hand, and increasing the rate constant of the Na+/H+, on the other. PMID- 1613979 TI - [Molecular structure and regulation of cyclooxygenase]. AB - Prostaglandin (PG) endoperoxide synthase is a bifunctional enzyme with fatty acid cyclooxygenase activity (arachidonic acid----PGG2) and PG hydroperoxidase activity (PGG2----PGH2). The primary structure of the enzyme was determined recently by cloning and sequencing the cDNAs for sheep and mouse enzymes and the genomic DNA for the human enzyme. Aspirin selectively inhibits the fatty acid cyclooxygenase activity but not the PG hydroperoxidase activity by acetylating the serine #506. Several lines of evidence suggest that cyclooxygenase enzyme is inducible by several biofactors, such as EGF, TGF-beta, IL-1, and epinephrine. Furthermore, it has been recently suggested that glucocorticoids inhibit the synthesis of the enzyme by the conversion of cyclooxygenase mRNA into a cryptic, untranslatable form. PMID- 1613980 TI - [Protein-tyrosine phosphorylation of human platelets and its function]. AB - Addition of ionophore A23187 to washed human platelets caused a time- and dose dependent increase in the phosphotyrosyl content of 135, 124 and 76 kDa proteins. Platelets loaded with intracellular Ca2+ chelator 5,5'-demethyl-bis-(o aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid before addition of A23187 exhibited no protein-tyrosine phosphorylation. Replenishment of such platelets with extracellular CaCl2 restored A23187-induced protein-tyrosine phosphorylation. Upon stimulation with A23187, both aspirin and ADP scavengers treated platelets exhibited protein-tyrosine phosphorylation without phosphoinositide hydrolysis or protein kinase C activation. Its protein-tyrosine phosphorylation was not inhibited by ML-9, a selective inhibitor of myosin light chain kinase. Genistein, a selective inhibitor of protein-tyrosine kinase, inhibited A23187-induced platelet aggregation but not secretion. These data show (a) that A23187 stimulates protein-tyrosine phosphorylation by elevation of intracellular Ca2+, (b) that A23187-induced protein-tyrosine phosphorylation is independent of formation of endoperoxides/thromboxane A2, released ADP, phosphoinositide hydrolysis, protein kinase C activation, fibrinogen binding and myosin light chain kinase, and (c) that A23187-induced protein-tyrosine phosphorylation may be involved in platelet aggregation but not in secretion. Furthermore, a synergistic effect of A23187 and protein kinase C activators in stimulating protein-tyrosine phosphorylation is suggested. PMID- 1613981 TI - [Intracellular Ca2+ behavior and activation of calpain-I in activated platelets]. AB - A relationship between intracellular Ca2+ concentration ([Ca2+]i) and calpain-I activation and change in subcellular localization of the enzyme in activated platelets were investigated. The [Ca2+]i exhibited a biphasic response after stimulation with thrombin. Activation of calpain-I was measured by determination of the appearance of active 76 and 78 kDa forms accompanying the disappearance of the 80 kDa form, the inactive form, on immunoblots. Calpain-I was activated dependent on the extent of the initial elevation of [Ca2+]i. For maximum activation (60%) 300-500 nM [Ca2+]i was required and half-maximal activation occurred at 160-220 nM [Ca2+]i. The active 76 kDa form was observed only in the fraction containing subcellular organelles and plasma membrane of activated platelets. It was demonstrated that the localization of calpain-I was changed from the cytosol to the membrane and calpain-I was activated on the membrane by Ca2+, elevated through the initial elevation after activation of platelets. PMID- 1613982 TI - [Amplification and inhibition of platelet function by serum lipoproteins]. AB - Low-density lipoprotein (LDL) at a concentration of 100 micrograms/mL, which is near the dissociation constant (Kd) of LDL-binding, had a maximal stimulatory effect on agonist-induced platelet aggregation. Anti-LDL receptor monoclonal antibody (C-7), like native LDL, induces a transient increase in intracellular Ca2+ and a shape change of human platelets. On the other hand, high-density lipoprotein (HDL) inhibited platelet function. ApoE-rich HDL, as well as, apoE.DMPC potently inhibited platelet aggregation in a dose-dependent manner. ApoE.DMPC stimulated the release of cholesterol into the supernatant, suggesting that apoE plays a major role in the inhibitory effect of apoE-rich HDL in platelet function, presumably due to the release of cholesterol from the plasma membrane. PMID- 1613983 TI - [Study on fibrinolysis and platelet function]. AB - The aim of this study is to evaluate the relationship between tissue plasminogen activator (tPA)/PA inhibitor (PAI) complex and PAI, and platelet in the circulating blood. tPA/PAI complex and active PAI (act PAI; Teijin Co., Japan), and PAI antigen (PAI ant; Biopool AB, Sweden) were assayed by enzyme immunoassay (EIA). The mean concentrations (ng/10(9) platelets) in supernatant from lysate of platelet rich plasma (PRP) and washed platelets were 27.1 +/- 9.2, 1.5 +/- 1.2 in tPA/PAI complex, 188.7 +/- 46.1, 83.3 +/- 7.5 in act PAI and 236.2 +/- 41.6, 191.9 +/- 45.1 in PAI ant, respectively. PRP was mixed with ADP (10(-5), 10(-4), 10(-3) M), for 3 min and the supernatant after centrifugation then was provided for assay of PAI and tPA/PAI complex. Concentrations of act PAI, PAI ant and tPA/PAI complex dose-dependently increased with ADP. Almost the same results were obtained, when collagen and other agents were used instead of ADP. This study revealed that platelets contained quantities PAI (as free PAI) and released PAI during aggregation, and that a part of the PAI immediately formed a complex with tPA. Those findings suggested that platelets may play an important role on the formation of thrombus, in the way of anti-fibrinolysis, in addition to novel platelet functions, such as aggregation. PMID- 1613984 TI - [Arterial intimal thickening]. AB - Disturbances in the integrity of the arterial endothelium are considered to be a primary event in the pathogenesis of atherosclerosis. Platelets do not adhere to the intact endothelium but with removal of the endothelium, a thrombotic response to the exposed thrombotic subendothelium occurs. With time, proliferation of smooth muscle cells occurs in the inner-most part of the media beneath the thrombus, and the proliferated smooth muscle cells migrate beyond the internal elastic lamina to invade the thrombus and organize it. A growth factor released from activated platelets (PDGF) stimulates smooth muscle cell proliferation. At the same time, the endothelium, adjacent to the thrombus, proliferates and covers the organizing thrombus from its margin. Thus, localized flat or raised intimal thickenings are formed from organization of mural thrombus or repair of intimal injury. There is much evidence that the release of platelet constituents can damage the vessel wall. Our study clearly demonstrated that material released from situ platelet-rich mural thrombi into the arterial circulation can cause endothelial damage and promote the proliferation of smooth muscle cells in the intima, downstream, and in remote segments of the arterial wall, without apparent endothelial denudation. PDGF, together with other growth factors, is also considered to be involved in smooth muscle cell proliferation in this case. PMID- 1613985 TI - [Inhibition of serotonin-induced platelet aggregation by endothelins]. AB - Endothelins are a family of three peptides that act as local hormones in all mammalian species. They were found to inhibit rabbit and dog platelet aggregation in vivo, whereas no effect was observed in vitro. In order to investigate the possible interaction between endothelins and human platelet serotonergic receptors, their effect on the platelet aggregation, induced by serotonin, was studied. Endothelin-1, -2 and -3 had a dual action for platelet aggregation induced by serotonin. When added simultaneously to serotonin endothelins aggregatory response to this amine was potentiated. On the contrary, preincubation of platelet suspension with endothelins resulted in a concentration dependent inhibition of serotonin-promoted platelet response. Moreover, endothelin-1 inhibited serotonergic amplification of epinephrine-induced aggregation of platelets. It is proposed that endothelins bind to the platelet membrane and interact with serotonergic receptors and/or G proteins. The diverse effect of eodothelins on serotonin-induced aggregation of platelets may be due to stimulation of protein kinase C. PMID- 1613986 TI - [Arachidonic acid metabolism affected by cellular interactions regulating leukocyte adherence]. AB - Increased leukocyte adherence to endothelium is recognized to be the first step following the development of unstable angina and cerebrovascular disease. In this paper, the methods to determine leukocyte adherence and the conditions which influence the result of the assay are discussed. We administered aspirin, TxA2 synthetase inhibitor or TxA2 receptor antagonist to healthy volunteers. Leukocyte adherence was inhibited following the administration of these antiplatelet agents. The effect on leukocytes may prevent thrombosis formation. Although the role of the leukocyte adherence in the pathogenesis of thrombosis has not been fully elucidated. Several forms of stimuli may cause expression of adhesive glycoproteins, which have a RGD sequence, on the surface of leukocyte and thus lead to thrombotic formation. PMID- 1613987 TI - [Platelet membrane glycoprotein V and clinical significance of plasma GPVf 1 level]. AB - Thrombin hydrolyzes platelet membrane glycoprotein V (GPV) which has leucine rich repetitive modules specifically, and releases GPVf1 (fragment of N terminal in GPV). The GPV related antigen level in plasma will thus reflect activation of platelet in vivo. The ELISA assay to measure the concentration of GPV and GPVf1 in plasma using polyclonal anti-GPV antibody, was established. The concentration of GPV and GPVf1 in plasma by using polyclonal anti-GPV antibody was established. The concentration of GPV related antigen in plasma is significantly higher in patients with thrombosis and correlated well with thrombotic episodes. It was suggested that the measurement of plasma-GPV-related antigen level is a useful marker for the diagnosis of thrombosis or prethrombotic states. PMID- 1613988 TI - [Platelet-derived microparticles]. AB - The presence of platelet fragments or platelet-derived microparticles (MP) in blood is of great interest, because it could be used as a marker for increased destruction or activation of platelets followed by their aggregation and vesiculation. In addition to early electronmicroscopic observations, a variety of methods to detect MP in plasma and serum have been developed, including immunoelectrophoresis, radioimmunoassay and the immunofluorescence test using flow cytometric analysis. In these techniques, monoclonal antibodies directed against platelet membrane specific antigens, such as glycoprotein (GP) IIb/IIIa or GP I b, have been used to distinguish platelet microparticles from other components. From basic and clinical investigations, MP has proved to be increased in some physiological and pathological conditions, including blood clotting, thrombin and collagen-induced activation of platelets, mechanical trauma of platelets, and immune-mediated platelet destruction. Furthermore, it has been shown that a significant part of platelet procoagulant activity resides on these small vesicles (MP), released from the platelet plasma membrane, on activation. PMID- 1613989 TI - [11-Dehydro-TXB2 and 2,3-dinor-TXB2 as new parameters of TXA2 generation]. AB - Artifactual formation of thromboxane (TX) B2 during blood collection falsifies real value of TXB2 in plasma. A part (29.3%) of TXB2 is metabolized to 11-dehydro (DH)-TXB2 in several organs. 11-DH-TXB2 was not generated during blood collection or during serum formation. The peak amount of 11-DH-TXB2 after intravenous injection of TXB2 to rabbits was lower than that of TXB2, but the level of 11-DH TXB2 was kept 2-3 times higher than that of TXB2 even after more than 5 min. A half life of 11-DH-TXB2 is 45-60 min in the human. Large species differences were found. In human urine, 11-DH-TXB2 was excreted 1.5-5.8 times more than 2,3-dinor TXB2. Patients with ARDS and DIC, who received platelet transfusion, excreted increased amounts of 2,3-dinor-TXB2 and 11-DH-TXB2 in urine. 11-DH-TXB2 may be a useful parameter of TXA2 formation in pathological states. PMID- 1613990 TI - [Hemostatic control in platelet dysfunction and abnormality by DDAVP]. AB - DDAVP infusion shortens the bleeding time in patients with some types of platelet dysfunction and may be useful for hemostatic control. In order to clarify the mechanism of DDAVP to correct or bypass the release defect, we examined the effect in 17 patients with prolonged bleeding time, i.e., 11 with various kinds of platelet dysfunction, 4 with idiopathic thrombocytopenic purpura (ITP), 1 with chronic myelocytic leukemia (CML), and in an aspirin-ingested volunteer. DDAVP shortened the bleeding time in 9 patients with platelet dysfunctions, one with ITP, and the one aspirin ingested volunteer. No improvement was found in the aggregability and the retention rates, and no signs of activation occurred in the platelet shape. The RCof was elevated in all of the patients after the infusion. Our data suggests that DDAVP improves the hemostasis through primary aggregation and release of dense bodies, and not directly through an increase of RCof. PMID- 1613991 TI - [Detection of soluble forms of platelet membrane glycoproteins and its clinical significance]. AB - Soluble forms of surface membrane glycoproteins of various cell types have been identified as makers for in vivo or in vitro cellular events, in which the receptors are involved. Using mouse monoclonal antibodies, sandwich ELISA systems to quantitate plasma concentrations of two platelet glycoproteins in soluble form were set up: one is glycocalicin (GC), a proteolytic fragment of GP Ib alpha chain and the other is GMP-140 or CD62 (GMP) known as a target for leukocyte recruitment at vascular injury sites. As in vivo markers, GC is said to reflect platelet turnover. High levels of plasma GMP were detected in patients with thrombotic thrombocytopenic purpura, being presumably indicative of microcirculation disorder. During storage of platelet concentrates, plasma levels of both markers were increased in a time-dependent fashion over 10 days. This correlated with a decrease in the surface expression of the glycoproteins on platelets, suggesting that the soluble glycoproteins entering the supernatants by proteolysis would be an useful indicator for in vitro alteration of stored platelets surface. PMID- 1613992 TI - [Pharmacological aspects of a novel antiplatelet drug, E5510]. AB - E5510 is an antiplatelet agent, recently synthesized in Japan. It inhibited human platelet aggregation ex-vivo induced by collagen, arachidonic acid, ADP, PAF, epinephrine and thrombin. In addition, it inhibited platelet adhesion and release reaction. In animal models of thrombosis, oral administration of a low dose of E5510 inhibited thrombus formation. Studies on its mode of action suggest that E5510 blocks multiple pathways of platelet activation: inhibition of arachidonic acid release, cyclooxygenase and PDE. Using healthy volunteers, inhibition of platelet aggregation was demonstrated with 1 hour after a single dose of E5510 and continued for more than 8 hours. No inhibition was observed 24 hours after administration. E5510 is currently under clinical evaluations in patients with various thrombotic diseases. This paper also describes the results of its clinical trials regarding the efficacy and safety using the patients with essential thrombocythemia. PMID- 1613993 TI - [Antiplatelet effect of clopidogrel]. AB - Clopidogrel is a new thieno-pyridine derivative and has a more potent inhibitory effect on platelet aggregation, dependent on ADP rather than ticlopidine. In a phase I study performed in Japan, significant inhibition of ADP-induced platelet aggregation and prolongation of bleeding time was observed in the dose range of 25, 50 and 75 mg. These effects were comparable to 200 or 300 mg of ticlopidine. Antithrombotic effects have also been shown in experimental animal models. Clopidogrel is expected to reduce the incidence of neutropenia since smaller doses are sufficient to suppress platelet aggregation compared to ticlopidine. Clopidogrel has been proven to be a potent and well-tolerated antiplatelet agent for atherosclerosis patients at risk of thrombosis, in Europe. PMID- 1613994 TI - [Clinical and preclinical pharmacology of KC-764, a novel antiplatelet agent]. AB - Preclinical pharmacological studies showed that KC-764 was more potent and more selective in inhibiting platelet aggregation than aspirin. The concentration of KC-764 for inhibiting PGI2 production in the aorta was 70 times higher than that for inhibiting TXA2 in platelets. Antiplatelet action of KC-764 was augmented by plasma components. This augmentation by plasma may lead to selective antiplatelet activity. KC-764 has been investigated for platelet function in patients with chronic cerebral infarction. KC-764 at 10, 20 and 40 mg b i d, inhibited platelet aggregation induced by arachidonic acid, collagen, and ADP, and its potency was almost equal to aspirin at 100-330 mg daily. Plasma TXB2 levels were markedly depressed by KC-764 but plasma 6-keto-PGF1 alpha levels were not influenced. On the contrary, aspirin depressed both plasma prostanoids. These findings suggest that KC-764 can overcome the 'aspirin dilemma'. PMID- 1613995 TI - [Strategies for antiplatelet therapy-drug-fixed method and suppression-fixed method]. AB - The strategies for antiplatelet therapy and recent trends in the research field are reviewed. In addition to the approach to finding new drugs, basic research on the function of the platelet which should be suppressed and on how drugs should be used, is required for the improvement of the efficacy of antiplatelet therapy. Our approach to suppression-fixed antiplatelet therapy which is in contrast with the previous drug-fixed method and is based on a principle that aggregation and release are strongly suppressed by the use of aspirin plus ticlopidine close to the limit, found observations on primary platelet dysfunction is described. Preliminary results of this on the prevention of stroke indicate that recurrence was 0.88% per year in contrast with the 4.3% in a group with normal platelet function and 5-15% in groups without antithrombotic therapy in Japan. PMID- 1613996 TI - [Benefits and risks of antiplatelet therapy. A retrospective study]. AB - Seven hundred and forty-six patients with cerebral infarction (except those with cardiogenic embolism) were retrospectively studied to determine the effect of antiplatelet agents on the prevention of recurrence and the incidence of cerebral hemorrhage, as an adverse effect of the drugs. The average follow-up period was 26.5 months for the fatal cases and 41.3 months for the survivors. Cerebral infarction recurred in 41 patients (3.1%/year) during the period of administration of antiplatelet agents, while it occurred in 66 (5.4%/year) untreated patients (p less than 0.01). Cerebral hemorrhage occurred 14 times in 14 patients; 7 (0.5%/year) during the antiplatelet treatment and 7 (0.6%/year) during the period without antiplatelet agents. No evidence was found that cerebral hemorrhage was promoted by antiplatelet agents. PMID- 1613997 TI - [Antiplatelet therapy in cardiac diseases]. AB - 1) Myocardial infarction (MI): Aspirin (160-300 mg/day) therapy started immediately after the onset, with or without simultaneous coronary arterial thrombolytic therapy, reduces the mortality rate in vascular diseases, including MI, and prevents reinfarction. Maintenance therapy with the same dosage is also recommended. 2) Angina pectoris: In unstable angina, aspirin in a dose of 300 mg/day for 2 years reduces the mortality and the incidence of MI. Ticlopidine decreases anginal attacks in a few cases of angina at rest. 3) Coronary artery bypass grafting (CABG): Long-term administration of 325 mg aspirin/day should be started on the day of surgery and combined with 200-400 mg dipyridamole/day administered from 2 days before to 1 week after the surgery. 4) Percutaneous transluminal coronary angioplasty (PTCA): Current antiplatelet drugs prevent post procedural acute coronary occlusion but not late restenosis. PMID- 1613999 TI - [Inhibitory effect of activated protein C and heparin on arterial thrombosis]. AB - Activated protein C (APC) exerts an anticoagulant effect by inactivating coagulation factors Va and VIIIa, preferentially on the surface of the cell membrane, and may enhance fibrinolysis by inhibiting PAI-1. APC inhibits venous and microvascular thrombosis, as well as, platelet-rich thrombus formation on the Dacron graft inserted in the arteriovenous shunt. We examined the effect of APC and heparin on arterial thrombosis using small mesenteric arteries of the rat, in which platelet-rich thrombus formation was induced by segmental deep vessel injury and the changes were monitored using a video-microscope system. Both APC (0.9 and 3.0 mg/kg, iv) and heparin (300 and 1000 U/kg) inhibited thrombus formation similarly. APC did not prolong APTT compared with heparin. APC may inhibit arterial thrombosis after vascular damage without serious bleeding side effects. PMID- 1613998 TI - [Anti-thrombotic and anti-atherogenic action of eicosapentaenoic acid]. AB - Epidemiological studies performed in Greenland Eskimos and Japanese indicated that ingestion of fish meat rich in omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), reduces the incidence of cerebro- and cardiovascular thrombotic diseases. Therefore, the effect of administration of purified EPA, derived from sardine oil, on hemorrheological properties and serum lipids in patients with thrombotic disorders was studied. Dietary supplementation of EPA resulted in decrease in platelet aggregability with reduction of TXA2 production, prolongation of bleeding time, decrease of platelet adhesiveness, increase of red cell deformability, and improvement of serum lipid concentration. Decrease in platelet TXA2 production may be ascribed to the decrease in arachidonate (AA) content of platelet membrane, inhibition of AA release from platelet membrane and competitive inhibition of AA metabolism at the level of cyclo-oxygenase, by EPA. Administration of EPA increased PGI2 production in the rat thoracic aorta and co culture of rat aorta smooth muscle cell with EPA also increased PGI2 production, but suppressed smooth muscle cell proliferation. This may be explained by a EPA derived peroxide stimulation of cyclo-oxygenase activity. Administration of EPA decreased platelet-derived growth factor (PDGF) production in rat peritoneal macrophages. In EPA-rich peritoneal macrophages from rat given EPA, incorporation of acetyl LDL and accumulation of cholesterol in macrophages decreased. This may indicate that dietary supplementation of EPA suppress foam cell formation. An interesting finding is that EPA-rich LDL obtained from rabbits given EPA is less susceptible to Cu(2+)-catalyzed oxidative modification. This seems to indicate that EPA may also suppress lipid peroxidation of lipoprotein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614000 TI - The aging of the aged: challenges for gerontology & geriatrics in the United States. AB - It comes as no surprise that global graying will be one of the most pressing issues of the coming century. The most rapidly growing age group in all developed countries is the one with persons aged 85 and older. Often referred to as the "oldest old", the aging of the aged reflects a universal concern being experienced in the United States as well as in other industrialized countries, such as Japan. This paper addresses the challenges that such changes present for gerontology and geriatrics. Contextual projections of population trends and of life expectancy, as well as actual health care costs and estimated government health care expenditures will be compared for the United States and for Japan. Among the geriatric challenges being confronted are (1) the need to separate aging from disease, (2) the need for more geriatric centers and available geriatricians to serve the aged, (3) the introduction of health care strategies of prevention and case management, (4) responses to the notion of health care rationing, and (5) the ultimate importance of research ranging from the biological and molecular to the behavioral, social, and health service delivery. Global aging presents a gerontological imperative that may best be understood by examining policy recommendations and future policy decisions. PMID- 1614001 TI - [Studies on atherosclerosis with an animal model]. AB - Atherosclerosis is a fundamental cause of life-threatening disorders, such as ischemic heart disease or stroke. Therefore, prevention and treatment of atherosclerosis is a matter of importance. In atherosclerotic lesions, there are many foam cells which contain large amounts of cholesteryl ester. In particular, most of these foam cells in the early stage of atherosclerosis derive from monocytes/macrophages. Today, foam cell transformation of macrophages in subendothelial space is considered to occur by a mechanism in which macrophages take up oxidized low density lipoprotein. We have already discovered that atherosclerosis of Watanabe heritable hyperlipidemic rabbits, an animal model for hereditary hyperlipidemia and severe atherosclerosis, could be prevented by probucol. This drug was originally developed as an antioxidant, and the mechanism of prevention of atherogenesis with this drug is considered that it prevents oxidative modification of LDL. On the other hand, probucol also causes regression of xanthoma in patients with familial hypercholesterolemia. This effect implies that probucol can be effective for treatment of atheromatous lesions, because xanthoma is a lesion which consists of macrophage-derived foam cells. However, the precise mechanism of probucol in causing regression of xanthoma has not been clarified. Considering these observations, we paid special attention to the oxidative modification of high density lipoprotein (HDL). HDL makes contact with foam cells in subendothelial space and stimulates efflux of cholesterol. This is the very place where oxidative modification of LDL is considered to occur. Therefore, it is rational to attempt to determine what would happen when HDL is oxidized and whether probucol could prevent oxidative modification of HDL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614002 TI - [Pathophysiology of osteoporosis from animal experimental point of view]. PMID- 1614004 TI - [The search for an animal model for the study of dementia]. PMID- 1614003 TI - [Clinical aspects of bone mineral content in osteoporosis]. PMID- 1614005 TI - [Assessment and treatment of patients with dementia of the Alzheimer type]. AB - Recently more than a dozen clinical trials for dementia of the Alzheimer type (DAT) have been conducted in Japan using almost the same diagnostic criteria and assessment procedures. Cholinomimetic drugs such as AChE or M1 agonist are the most common in the current clinical drug trials. DSM-IIIR and NINCDS-ADRDA are usually employed as diagnostic criteria. In the recent report on the sensitivity and specificity of these diagnostic criteria, it has been indicated that the clinician or researcher who wishes to ensure that patients classified as DAT are more likely DAT should choose DSM-III, whereas the investigator who wishes to include the greatest number or DAT cases, seldom assigning a diagnosis of no DAT to a true case, should choose NINCDS-ADRAD. Also, development of exclusion criteria for DAT would be essential to improve interrater reliability of these diagnostic criteria. In the recent clinical trials outside Japan, a dual assessment procedure consisting of objective psychometric test(s) to assess cognitive impairment and global clinical impression of change is a standard method to evaluate the clinical efficacy of drugs for DAT. In psychometric tests, Alzheimer's Disease Assessment Scale (ADAS) is the most common in the US and Hasegawa's Dementia Scale (HDS) in Japan. A Japanese version of ADAS-cog. has been already developed for use in clinical trials in Japan. Also, HDS has recently been revised to improve the sensitivity of the test. In addition, Clinical Dementia Rating (CDR) that is one of the common measures staging severity of dementia in Japan might be a better alternative to the conventional Clinical Global Impression of Change (CGIC) in the US.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614006 TI - [Quantitative X-ray CT analysis of calcification of the abdominal aorta and its relationship to obesity]. AB - Quantitative analysis of abdominal aorta calcification by X-ray CT is a useful method for non-invasive diagnosis of atherosclerosis. We recently examined the relationship between the X-ray CT measurement of abdominal aorta calcification and the degree of obesity. For this purpose, the body mass index (BMI) and the subcutaneous fat thickness (determined by X-ray CT at the umbilical level) were analyzed in relation to the abdominal aorta calcification index (ACI) in 845 patients (453 males and 392 females aged 40-79 years). Patients with BMI under 20 were classified as "lean", those with BMI between 20-26 as "normal" and those with BMI over 26 as "obese". 1. Among males, the ACI was highest in lean individuals and lowest in obese individuals. The difference in ACI between lean and obese males was significant in the middle aged group (40-65 years). Among females, no relationship was observed between the degree of obesity and ACI. 2. Among males, ACI was higher in individuals with low subcutaneous fat thickness and lower in individuals with greater subcutaneous fat thickness. The difference was significant in the middle aged group. Among females, no relationship was observed between the two parameters. 3. When the visceral fat to subcutaneous fat ratio (V/S) in 85 males and females aged 60-69 years was analyzed in relation to ACI, ACI tended to decrease as the V/S increased, in both males and females. 4. Relationships between BMI and subcutaneous fat thickness, between BMI and lipids and between lipids and ACI were also analyzed. PMID- 1614007 TI - [Guanidino compounds in the elderly]. AB - To examine the metabolism of guanidino compounds in the elderly, we measured the serum concentrations of urea nitrogen, creatinine (Cr), guanidinoacetic acid (GAA) and creatine (CR) in middle-aged and elderly subjects. We also measured muscle mass in the elderly. The elderly subjects tended to have lower serum GAA concentrations than middle-aged subjects. On the contrary, CR concentrations of elderly subjects were higher than those of middle-aged subjects. Bedridden elderly subjects tended to have lower serum GAA concentrations and lighter muscle mass than ambulatory elderly subjects. On the contrary, serum CR concentrations of bedridden subjects were higher than those of ambulatory subjects. CR is an essential substance for muscle energy metabolism. These results indicate that high serum CR concentrations due to low CR metabolism in skeletal muscle might suppress glycine amidinotransferase (GAT) activity, resulting in decreased GAA production in the elderly. PMID- 1614008 TI - [A statistical analysis of factors influencing standing balance, activity of daily living and ambulation in hemiplegic patients]. AB - This study was undertaken to investigate several factors influencing standing balance, activity of daily living and ambulation in hemiplegic patients after cerebro-vascular diseases. A statistical analysis of 121 hemiplegic patients with unilateral supratentorial lesions showed that age, severity of muscle weakness of involved or uninvolved extremities, unilateral spatial neglect and the sense of toe position had influence on standing balance, activity of daily living or ambulation. The patients were divided into five groups based on the degree of unilateral spatial neglect, evaluated by their copies of two daisies who omitted more than three quarters, three quarters, half, one quarter and none of the figures were defined as the USN-4, USN-3, USN-2, USN-1 and no involvement groups, respectively. Those who belonged to the USN-2 group had significantly lower scores for activity of daily living than those who belonged to the no involvement group. In the USN-2 group, 7 of the 8 patients could not keep standing for 50 seconds, while in the no involvement group, this was the case in only 1 of the 15 patients. Activity of daily living scores or sway area during standing showed no statistically significant differences between the USN-1 and no involvement groups. These results suggested that severe or moderate unilateral spatial neglect is one of the most important factors influencing standing balance and activity of daily living. PMID- 1614009 TI - [Electrocardiographic criteria for the diagnosis of the left septal fascicular block and its frequency among primarily elderly hospitalized patients]. AB - Characteristic electrocardiographic findings of the left septal fascicular block consist of a prominent anterior QRS force. Therefore, the following criteria were proposed for the diagnosis of left septal fascicular block, based on the normal limits of the R and S waves and R/S of V1 and V2. (1) Right ventricular hypertrophy, complete right bundle branch block, preexcitation (Type A), high posterior infarction, hypertrophic cardiomyopathy and abnormality of the thorax or intrathoracic tissues which might cause marked counterclockwise rotation around the longitudinal axis of the heart, should be excluded. (2) One of the following two criteria should be satisfied. (i) R/Sv1 greater than 2, and Rv1 greater than or equal to 5 mm, (ii) R/Sv2 greater than 2, and Rv2 greater than or equal to 15 mm, or Sv2 less than 5 mm. The frequency of left septal fascicular block diagnosed by these criteria was 3.5% among all patients of a hospital mainly consisting of elderly patients. This frequency was less than that of the left anterior fascicular block or complete right bundle branch block, but it was higher than that of the complete left bundle branch block or bilateral bundle branch block. PMID- 1614010 TI - [Contributing factors to intellectual impairment in patients with multiple lacunar infarctions]. AB - The author investigated factors leading to intellectual impairment in patients with multiple lacunar infarctions. The subjects consisted of 40 patients with multi-infarct dementia (MID) and 17 nondemented patients with multiple infarctions (MI) who showed multiple lacunar infarctions in the deep penetrating arterial territory on CT. MID patients showed more marked and extensive periventricular lucency (PVL), a higher degree of ventricular index (VI) measured on CT, and were of a higher age, and had poorer activity of daily living (ADL) compared with MI patients. There were significant correlations between the PVL score, VI, ADL score, age and Hasegawa's dementia rating score (HDS). However, no significant differences in sex, site of infarct, and the count of low density areas reflected lacunar infarction on CT, and vascular risk factors were shown between MID and MI patients. Multiple regression analysis demonstrated that the PVL score and VI showed the highest partial correlations for HDS, and that the ADL score and age were also independently contributing factors. Our results suggest that deep white matter lesions observed as PVL on CT and ventricular enlargement were the most important factors contributing to intellectual impairment in patients with multiple lacunar infarcts, and that physical factors such as ADL and age can be considered to be related to the development of dementia. PMID- 1614011 TI - [Isolated splenic tuberculosis]. AB - A case of splenic tuberculosis is reported. The patient was a 79-year-old man who was admitted to the Tokyo Metropolitan Geriatric Hospital because of high fever and loss of body weight. Several finger-tip sized superficial lymph nodes were palpable in bilateral inguinal regions. The intermediate PPD skin test was positive. However, there was no evidences of active tuberculosis on the chest roentgenogram. The computed tomogram of the abdomen showed moderate enlargement of the spleen with multiple low density areas and several swollen lymph nodes in the para-aortic region. Although a lymph node of the inguinal region was resected for the pathologic examination, it showed no specific changes. In order to obtain a final diagnosis, laparotomy was performed. The spleen was markedly enlarged and nodular in appearance. No abnormal findings were observed in the other abdominal organs. Splenectomy was carried out. Numerous yellowish nodules, varying from 0.1 to 5 cm in diameter, were observed on the cut surface of the resected spleen (20 x 20 x 8 cm, 700 g). The bacteriologic examination revealed acid-fast bacilli. The fever subsided after splenectomy and following antituberculous therapy. Recently, isolated tuberculosis of the spleen has become very rare. Since 1965, only six cases in five reports can be found in the English, French and German literature. The present case is considered to be one such very rare cases of tuberculosis. Although splenic tuberculosis is rare at the present time, splenic tuberculosis should be included in the differential diagnosis of fever of unknown origin with splenomegaly. PMID- 1614012 TI - [Progressive changes in the coronary arteries in patients with ischemic heart disease after aortocoronary bypass]. AB - To examine the time course of changes in the coronary arteries in patients with coronary heart disease after aortocoronary bypass (ACB), the authors studied 2 groups of patients: (1) 23 who had conservative treatment and (2) 23 who were selected for ACB. Repeated angiography was performed 14.6 +/- 2.5 months after the initiation of the study. Following ACB, changes in lesions were observed in 17 coronary artery segments in 39.1% of the patients. Grafted artery stenoses largely proximal to the site of transplantation became progressive. There was a relationship between the changes in coronary arteries to graft patency. In Group 1, the time course of coronary atherosclerosis was found in 8 segments in 26% of the cases. Atherosclerosis progressed in all artery segments virtually in a steady way. Application of vein grafts may change intracoronary hemodynamics, creating conditions for more rapid and common progression of coronary artery lesions. PMID- 1614013 TI - [Arteriosclerosis of the right gastro-omental artery]. AB - The right gastroepiploic artery is most frequently used for direct myocardial revascularization. In this connection, its histological study was performed to reveal the atherosclerosis incidence in persons from different age groups who had apparent signs of coronary atherosclerosis. Twenty one arteries taken from adult cadavers at the age of 35-85 years were examined. The arteries with normal were 28.6%, those with Degree I alterations were 52.4%, those with Degree II alterations were 19%. Degrees III and IV alterations were not detected. Morphological studies indicated that hemodynamically significant right gastroepiploic artery lesions were found in 19% of cases, mainly in subjects above 60 years. The artery may be used in coronary surgery as a shunt with a good prognosis of its performance. PMID- 1614014 TI - [Changes in lipid metabolism in patients with arteriosclerosis obliterans after charcoal hemoperfusion and hypolipidemic therapy in the preoperative period]. AB - The paper analyzes the results of the treatment of 26 patients with atherosclerosis obliterans of the lower extremities, which has been performed to make an intensive hypolipidemic preparation for an operation. The comprehensive approach based on the combination of medication (nicotinic acid, and its derivatives, cholestyramine, and SKH -2K charcoal hemoperfusion ) and efferent therapy reduced the plasma levels of total cholesterol by 27%, triglycerides to 48%, low density lipoprotein cholesterol to 40%, and increased high density lipoprotein cholesterol up to 72%. The similar course therapy may be repeatedly used in a follow-up of this group of patients. PMID- 1614015 TI - [Study of the role of adrenergic vasoconstriction in the development of dynamic coronary obstruction in patients with stress-induced stenocardia]. AB - The aim of the present investigation was to evaluate sympathetic vasoconstrictor influence and to define its role in the formation of coronary occlusion in patients with effort angina. The investigation covered 22 patients with Functional Class II-III stable effort angina. To detect vasoconstrictor responses on exercise and to identify their adrenergic component, pair bicycle tests were performed before and after administration of nitroglycerin and pratsiol. Repeated bicycle tests were conducted twice a day: at 10-11 a.m. and at 3-4 p.m. to study spontaneous exercise tolerance variations confirming the presence of dynamic coronary occlusion. The examinations indicated that in 18 patients the exercise resulted in functional major artery narrowing, aggravating the organic stenosis. Activation of smooth muscle alpha-adrenoreceptors is of a definite significance in the genesis of dynamic coronary occlusion in 50% of all the examinees. PMID- 1614016 TI - [Prognostic significance of various qualitative and quantitative indicators of coronary angiography in patients with unstable stenocardia]. AB - The coronary bed was qualitatively and quantitatively examined in 41 patients with unstable angina pectoris. The patients were divided into two groups: (1) those with uncomplicated angina and (2) those with complicated angina in relation of follow-up (mean 3.1 +/- 0.8 years) findings. In patients with a poor coronary heart disease outcome a symptom-related lesion was more frequently located mainly in the left coronary trunk during clinical manifestations of unstable angina pectoris, along with more severe overall lesion in the coronary bed. They had also higher incidence rates of complicated lesions and higher values of three quantitative parameters (stenosis extent, the mean and proper diameters of a stenotic segment in the symptom-related vessel) determined by semiautomatic stenosis configuration analysis. PMID- 1614017 TI - [Differential methods of physical training of patients with ischemic heart disease in early periods after aortocoronary bypass and their effect on the indicators of central hemodynamics]. AB - Seventy two patients with coronary heart disease who had undergone aortocoronary bypass grafting were followed up. In the early postoperative periods (on day 16) the patients had ergometer exercise testing along with chest massage. In patients with complete myocardial revascularization and without complications, the exercise was 50% of the individual threshold capacity, followed by its correction every 7 days after control bicycle ergometry. In patients with incomplete myocardial revascularization or with intra- and postoperative complications, exercises with steady capacity (50% of the threshold capacity) were performed, by enhancing its exposition in a gradual manner. A course of physical training (15 18 studies 5 times a week) resulted in improvement of the patients' clinical condition, and caused a training effect and positive alterations in central hemodynamic parameters in patients with both hyper- and hypokinetic hemodynamic baselines. PMID- 1614018 TI - [Use of an implanted spinal neurostimulator in treatment-resistant stenocardia]. PMID- 1614019 TI - [Effect of acetylsalicylic acid on the indicators of thrombocytic hemostasis in patients with myocardial infarction]. AB - The examination of 50 patients with acute myocardial infarction indicated that enhanced platelet functional activity was a prognostically unfavourable sign and associated with a higher risk for myocardial infarction complications. The application of aspirin, 250 mg daily, in patients with high platelet functional activity in the acute period of the disease failed to produce a beneficial antiaggregatory effect. PMID- 1614020 TI - [Differential selection of anti-anginal drugs in stable stenocardia in relation to the data of central and intracardiac hemodynamics]. AB - Rheography and echocardiography were used to study central and intracardiac hemodynamic parameters in 196 patients with Functional Classes I-II from the screening of the main antianginal drugs during an acute pharmacological test under bicycle ergometric monitoring. It was established that the hemodynamic type of circulation and left ventricular end-diastolic and end-systolic volumes may be used as criteria for the differential choice of antianginal agents. The values of these parameters are given for sustac, propranolol, verapamil, nifedipine and sustac plus propranolol. PMID- 1614021 TI - [Changes in plasma lipid and apoprotein levels in patients with ischemic heart disease after hemosorption]. AB - All the patients who had undergone a course of non-specific hemosorption (HS) for clinical indications showed lower plasma lipid levels and largely lower triglyceride concentrations. The patients with hypercholesterolemia alone simultaneously displayed decreased levels of cholesterol, high density lipoproteins, and apoprotein A-I. Apoprotein B levels reduced in patients having normal lipid values and in those with isolated hypercholesterolemia. The changes in the levels of lipids and apoproteins were different for 2 weeks after hemosorption in relation to the baseline lipid spectrum. The patients with coronary heart disease with hyperlipidemias had positive trends in lipid spectral changes: the parameters of atherogenic classes of lipids tended to decrease, whereas those of antiatherogenic lipid classes tended to show a slight increase. There was a negative direction in the dynamics of the studied parameters in renal patients, in those who had normal baseline lipid values, and in those with isolated hypo-alpha-cholesterolemia, i. e. higher plasma cholesterol and triglyceride, low density lipoprotein cholesterol and apoprotein B levels. PMID- 1614022 TI - [Interaction of hyperbaric oxygenation with nifedipine and propranolol at the level of autonomic regulation of the heart in patients with angina pectoris]. AB - Thirty three males suffering from coronary heart disease, Functional Classes II III exercise-induced angina pectoris were examined for changes occurred in autonomic cardiac regulatory parameters under the influence of a normobaric oxygenation session (control), a hyperbaric oxygenation session (oxygen pressure 1.5 atm, duration 40 min), and combined normo- and hyperbaric oxygenation with nifedipine (oral corinfar, 20 mg, n = 18), and propranolol (oral inderal, 40 mg, n = 15) sessions. Variation of pulse and statistical analysis of cardiac rhythm were used in the study. The baseline autonomic tone and autonomic provision isometric exercise were evaluated. A single hyperbaric oxygenation session in this mode during isometric exercise was shown to diminish the sympathetic activation and increased heart rate which had been caused by nifedipine, by decreasing its central sympathetic effect and increasing neuroeffector cholinergic activity. The hyperbaric oxygenation session in combination with propranolol induced a supplementary reduction in sympathetic activity and its effects on cardiac rhythm via the humoral regulatory pathway by potentiating the negative chronotropic effect of the drug. PMID- 1614023 TI - [Physical activity and physical work capacity of patients with initial manifestations of cerebrovascular disorders in arterial hypertension]. AB - The routine protocol of general and neurological examinations and some special questionnaires were used to examine physical activity (FA) and physical working capacity (FWC) in a random population from one of the Moscow districts which included 1200 persons (males and females aged 30-64 years). The majority of the examinees were those who had slight and moderate exercises, mainly sitting work, did few or no physical exercises. The proportion of persons with low physical activity increased with age both among males and females. The ratios generally remained despite the presence of early signs of abnormal blood supply. Bicycle ergometer testings showed a significant reduction in the physical working capacity of the patients with abnormal brain blood supply, in a greater extent, in arterial hypertension. Decreased functional activity and functional working capacity may regarded as one of the risk factors for cerebrovascular disorders, in arterial hypertension in particular, and should be borne in mind in implementing preventive measures. PMID- 1614024 TI - [Pathogenesis of angina pain (concerning the article by V.S. Volkov "The role of spasm in the pathogenesis of stenocardia")]. PMID- 1614025 TI - ["The role of spasm in the pathogenesis of stenocardia"]. PMID- 1614026 TI - [Isoptin in cardiologic practice]. PMID- 1614027 TI - [X syndrome]. PMID- 1614028 TI - [Hypertensive crisis]. PMID- 1614029 TI - [Early intravital diagnosis of pericardial mesothelioma]. PMID- 1614030 TI - Axial heterogeneity of adenosine transport and metabolism in the rabbit proximal tubule. AB - Transport and metabolism of adenosine were studied in the S1, S2, and S3 segments of the rabbit proximal renal tubule. Isolated segments were perfused in vitro with uniformly labelled 14C-adenosine to measure the lumen-to-bath flux of adenosine. This flux rate was measured by the disappearance of 14C from the luminal fluid (JD) and simultaneously by the appearance of 14C in the bathing solution (JA), expressed as femtomoles per minute per millimeter of tubule length (fmol.min-1.mm-1). At a perfused concentration of 83.3 microM adenosine, when corrected for metabolism, the JDs for adenosine in the S1, S2, and S3 segments were 735, 212, and 273, respectively. JAs, corrected for metabolism, were 0, 0, and 4.8 fmol.min-1.mm-1 for the S1, S2, and S3 segments, indicating that very little or no 14C-adenosine moved across the basolateral membrane. To correct for metabolism of 14C-adenosine, the perfusion fluid, collected fluid, tubular extract, and bathing fluid, from three tubules of each segment type, were analyzed by high-performance liquid chromatography to identify 14C-adenosine and its 14C-metabolites. At 83.3 microM, all segments metabolized adenosine extensively. Consequently, adenosine-5'-monophosphate (AMP) and inosine were found in tubule cells of all segments. Inosine also appeared in the collected fluid, but AMP did not. In S1 and S2 segments, none of the 14C in the bathing solutions could be identified and no adenosine was found. Of the small amounts of 14C found in bathing solutions from S3 segments, about 27% appeared to be adenosine, the rest were inosine and hypoxanthine or unidentified metabolites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614031 TI - Response of cortical collecting ducts from remnant kidneys to arginine vasopressin. AB - Chronic renal failure is associated with impaired urine concentration. Previous studies have demonstrated that cortical collecting ducts (CCD) from uremic rabbits (with remnant kidneys) have an impaired response to arginine vasopressin (AVP). To determine whether this defect is an early, integral component of compensatory renal growth by the remnant kidney, we studied the response of CCD derived from rabbits one week after 75% nephrectomy. At one week, hypertrophy and adaptation in sodium transport are fully developed, but azotemia and interstitial fibrosis are absent. The animals with remnant kidneys failed to respond normally to water deprivation and dDAVP (maximum urine osmolality 738 +/- 29.1 mOsm/kg compared to 1378 +/- 207 in sham operated). However, in isolated, perfused CCD from remnant kidneys, AVP stimulated hydraulic water permeability to the same extent as in normal CCD or CCD from sham operated animals. AVP-induced cAMP generation per mm tubule length was significantly higher in the CCD from remnant kidneys (137.4 +/- 14.5 fmol/mm) than in the control group (82.4 +/- 11.9 fmol/mm), but not different when expressed per micrograms protein. These studies demonstrate that one week after reduction in renal mass there is no defect in the response of CCD to AVP, suggesting that the mechanisms responsible for the hyposthenuria after loss of renal mass are not related to any intrinsic cellular changes that occur in CCD early during compensatory renal growth. PMID- 1614032 TI - Interactions of LDL and modified LDL with mesangial cells and matrix. AB - Hyperlipidemia may play a role in the progression of diabetic and other renal diseases. Low density lipoprotein (LDL) and other proteins including extracellular matrix components undergo nonenzymatic glycation in vivo. We examined the effects of glycation of LDL as occurs in diabetes (4 to 8%) on binding and uptake by mesangial cells and their proliferation. The glycation of LDL (g-LDL) significantly decreased its binding and uptake by mesangial cells by 15 to 20%, indicating that glycated LDL binds to the LDL receptor, but with lower affinity than LDL. Both LDL and g-LDL modestly stimulated [3H] thymidine incorporation into mesangial cells at 5 to 10 micrograms/ml. Native, oxidized (Ox LDL) and glycated LDL all bound to the extracellular matrix generated by rat mesangial cells in culture. The binding of LDL, Ox-LDL and g-LDL to mesangial matrix was two to four times higher than to mesangial cells. Binding of LDL and g LDL was significantly higher to glycolaldehyde modified matrix, which serves as an in vitro model for nonenzymatic glycation end-product cross-linking of matrix which occurs in long-standing diabetes. Based on these findings, we propose that glycation of LDL decreases its binding and uptake by the LDL receptor of mesangial cells and may slow its catabolism. Furthermore, LDL bound to extracellular mesangial matrix can undergo oxidation and generate cytotoxic LDL components. This process may be further enhanced by advanced glycation of the mesangial matrix in diabetes, contributing to glomerular pathology. PMID- 1614033 TI - Chronic neutral phosphate supplementation induces sustained, renal metabolic alkalosis. AB - The aim of the present study was to test whether intravenous neutral phosphate supplementation, recently shown in our laboratory to acutely stimulate proton secretion in the distal nephron, was able to induce a sustained metabolic alkalosis. Neutral Na and K phosphate supplementation for seven days, with equivalent reduction in chloride supply and unchanged intake of sodium and potassium, in ADX rats receiving fixed physiological doses of aldosterone and dexamethasone (group 1, N = 7), was responsible for a severe metabolic alkalosis (MA; delta [HCO3] 11 +/- 1.3 mM, and delta pH 0.11 +/- 0.06 unit). Metabolic alkalosis was at least in part of renal origin, since net acid excretion (NAE) transiently increased, principally due to an increment in titratable acid excretion rate. Balances were equilibrated for sodium and negative for chloride and potassium, which may have contributed to the severity of the MA. Chronic i.v. neutral Na phosphate, without change in potassium and chloride supply, in ADX rats receiving the same doses of steroids (group 2, N = 5), was responsible for a less severe MA (delta [HCO3] 7.5 +/- 0.9 mM, and delta pH 0.07 +/- 0.01 unit), also of renal origin. In this group, balances were positive for chloride and sodium and equilibrated for potassium. Finally, neutral Na and K phosphate supplementation with reduction in chloride supply in intact rats (group 3, N = 4) was also able to induce a MA (delta [HCO3] 5.5 +/- 1.8 mM, and delta pH 0.06 +/- 0.01 unit) of renal origin, with balances negative for chloride and equilibrated for potassium and sodium. In all groups, the generation and maintenance of MA probably resulted from stimulated proton secretion in the distal nephron, as suggested by the observed increase of PCO2 over HCO3 concentration ratio in the urine and a fall in urine pH despite augmented urinary buffer content throughout the phosphate infusion period. Glomerular filtration rate did not significantly vary in any group. In conclusion, chronic supplementation of neutral phosphate appears to stimulate per se proton secretion in the distal nephron, independently of sodium, chloride, and potassium balances, and adrenal steroid secretion. Thus neutral phosphate supplementation should be added to the previously known factors able to induce MA. PMID- 1614034 TI - Experimental model of lead nephropathy. I. Continuous high-dose lead administration. AB - This study followed the progression of lead nephropathy in male Sprague-Dawley rats (E) administered lead acetate (0.5%) continuously in drinking water for periods ranging from 1 to 12 months. Control animals (C) were pair-fed. Observations included renal pathology by light and electron microscopy, wet and dry kidney weights, and glomerular filtration rate (GFR) to assess renal function. Urinary excretion of lead, the enzymes N-acetyl-beta-D-glucosaminidase (NAG) and glutathione-S-transferase (GST), and brush border antigens (BB50, CG9, and HF5) were utilized to explore possible markers of kidney injury. GFR was increased significantly after three months of lead exposure, but was decreased significantly after 12 months. Kidney wet weights were significantly greater in E than C from three months on. Kidney dry weight/wet weight ratio was constant up to three months, but decreased in E at 12 months. Glomerular diameters were normal at all time periods; the nephromegaly was related primarily to hypertrophy of proximal tubules. Lead inclusion bodies were found in nuclei of proximal convoluted tubules and pars recta at all times. Tubular atrophy and interstitial fibrosis first appeared at six months, and increased in severity thereafter. Brush borders of proximal tubules were disrupted at one and three months, but recovered thereafter. Focal and segmental glomerulosclerosis was observed in 2 of 10 rats at 12 months. Arteries and arterioles remained normal at all time periods. Urinary NAG was elevated in E above C after three months of lead exposure. However, urinary NAG in C also increased with age, obscuring changes in the 12 month E rats. GST was elevated after three months of lead administration in E, not without an attendant age-related increase in C rats. In three-month E rats, urinary brush border antigens were increased above C, but were decreased at six and 12 months, correlating with the morphologic changes in brush border. We conclude that a high dose of lead in rats may initially stimulate both renal cortical hypertrophy and an increase in GFR. Later, the adverse effects of lead on the tubulointerstitium predominate, and GFR falls. The urinary marker, NAG, was abnormal in the early stages of the disease, but age-related changes obscured its utility at later stages; urinary GST appeared to be a more consistent marker of injury. PMID- 1614035 TI - Renal localization of the constitutive 73-kDa heat-shock protein in normal and PAN rats. AB - We purified the constitutive 73-kDa heat-shock protein (HSP73) from the bovine brain, and produced a specific antibody against the protein in a rabbit. On immunoblotting, the antibody cross reacted only with a protein band with a molecular mass of 73 kDa in a crude extract from normal rat kidneys, which was regarded as rat renal HSP73. The intrarenal immunohistochemical distribution of HSP73 was examined by using this antibody, on both normal rat kidneys and kidneys with puromycin aminonucleoside nephrosis. HSP73 was predominantly present in epithelial cells of the glomeruli and the tubules. In normal kidneys, HSP73 was generally localized in both the cytoplasm and the nucleus of these epithelial cells, except for proximal tubular epithelial cells. On the other hand, in kidneys with puromycin aminonucleoside nephrosis, HSP73 accumulated in the cytoplasm at a level higher than in the nucleus in association with the severity of renal dysfunction and proteinuria. These findings indicate that HSP73 is mainly expressed in glomerular and tubular epithelial cells in the kidney under a physiological condition, and that its expression changes from the nucleus to the cytoplasm under pathological conditions such as a protein overload to these epithelial cells. PMID- 1614036 TI - Production of extracellular matrix by glomerular epithelial cells is regulated by transforming growth factor-beta 1. AB - Transforming growth factor-beta (TGF-beta) has widespread effects on extracellular matrix production by many cultured cell lines and appears to play a role in the pathological accumulation of extracellular matrix that accompanies inflammatory and fibrotic diseases such as glomerulonephritis. Earlier experiments have shown that mesangial cells respond to TGF-beta 1 with a marked increase in the production of two chondroitin/dermatan sulfate proteoglycans, decorin and biglycan, but their production of other matrix components elevated in glomerulonephritis is not substantially affected by TGF-beta 1. Since the glomerular epithelial cells are also thought to contribute to matrix production in the glomerulus, we examined the ability of these cells to produce some of the nonproteoglycan matrix components in response to TGF-beta 1. Exposure of glomerular epithelial cells to TGF-beta 1 increased the production of fibronectin and type IV collagen, in addition to biglycan. Enhancement of the cell layer accumulation of laminin was also observed. These results show that TGF-beta 1 has a differential effect on extracellular matrix production by epithelial and mesangial cells from glomeruli. TGF-beta 1 released in the glomerulus secondary to injury could thus affect both cell types and lead to increased intraglomerular production of proteoglycans, whereas the increased fibronectin, type IV collagen, and laminin may primarily originate from the epithelial cells. PMID- 1614037 TI - Free cadmium activity in renal epithelial cells is enhanced by Mg2+ depletion. AB - Free Cd2+ uptake was determined by fluorescence techniques with the use of mag fura-2 in single epithelial MDCK cells. Cytosolic Cd2+ increased in a time dependent and concentration-dependent manner following the addition of cadmium to the external solution. The increment in cytosolic Cd2+ was greater in magnesium depleted cells relative to normal cells. Uptake in normal and magnesium-depleted cells was inhibited by the channel antagonist, verapamil, and increased with the agonist, Bay K 8644. These studies indicate that free Cd2+ may exist in the cell cytosol and Cd2+ uptake is greater following magnesium-depletion. These data support the notion that magnesium may provide a cytoprotective effect in cadmium toxicity. PMID- 1614038 TI - Essential fatty acid deficiency normalizes function and histology in rat nephrotoxic nephritis. AB - The central lipid abnormality in essential fatty acid deficiency (EFAD) is the lack of availability of arachidonic acid. To examine the role of total eicosanoid's biosyntheses in the pathology and pathophysiology of glomerulonephritis, EFAD was induced in weanling rats, which were then subjected to antiglomerular basement membrane antibody (NTS)-induced injury in adulthood. Glomerular dynamics (as assessed by micropuncture), quantitative histology, and eicosanoid generation rates were measured at two hours and two weeks post-NTS, and compared to those of standard diet-fed (STD) controls. Two hours post-NTS, and despite the occurrence of proteinuria in both EFAD and STD animals, glomerular dynamics were essentially normal in EFAD rats, whereas STD animals had reduced values for glomerular filtration rate (GFR) and renal plasma flow rate (RPF). At two weeks, severe histologic changes were observed in STD animals including mesangial and stalk hypercellularity, moderate sclerosis, and interstitial nephritis, coupled with heavy proteinuria and reduced GFR and RPF. In dramatic contrast, EFAD rats displayed totally normal glomerular structures and functions. In parallel, glomerular generation rates of prostaglandin E2 and thromboxane A2 were suppressed markedly in EFAD rats. Thus, EFAD confers complete protection against the histopathologic and functional sequelae of immune initiated injury in the glomerulus. The data suggest that the initial wave of complement-induced neutrophil infiltration (with resultant proteinuria) is not sufficient to perpetuate injury into the more destructive chronic phases. The results provide strong impetus for the design of more specific interventional therapies targeting the various enzymes and products of arachidonic acid metabolism in the attempts to control glomerular inflammation. PMID- 1614039 TI - Interactions of hypercholesterolemia and hypertension in initiation of glomerular injury. AB - In the Dahl S rat (DS), salt induces systemic and glomerular capillary hypertension associated with progressive glomerulosclerosis, while Dahl R rats (DR) remain normotensive, without glomerular abnormalities. Studies in experimental models have suggested that hypercholesterolemia may play a role in the development of glomerulosclerosis; however, it is unclear whether hypercholesterolemia alone, in the absence of hypertension, can initiate injury. To answer this question we induced hypercholesterolemia in salt-supplemented DS (DSC) and DR (DRC) by feeding a high cholesterol (4%) chow. Control rats (DS, DR) received high-salt, normal cholesterol chow. After eight weeks, DS and DSC developed equivalent hypertension (161 +/- 3 vs. 153 +/- 3 mm Hg, respectively, P = NS), while DR and DRC remained normotensive (138 +/- 5 vs. 131 +/- 5 mm Hg, P = NS; P less than 0.05 vs. DS and DSC). Cholesterol fed rats developed marked and equivalent hypercholesterolemia compared to controls (DS vs. DSC, 71 +/- 3 vs. 289 +/- 91 mg/dl, P less than 0.05; DR vs. DRC, 52 +/- 2 vs. 327 +/- 54 mg/dl, P less than 0.05). Hypertensive rats (DS, DSC) developed worse proteinuria and glomerular injury than normotensive rats (DR, DRC), but hypercholesterolemia exacerbated proteinuria and glomerulosclerosis only in DSC and not in DRC. Proteinuria significantly correlated with serum cholesterol in hypertensive rats (DS, DSC, P less than 0.05), but not normotensive rats (DR, DRC, P = NS). Furthermore, DSC had increased renal vascular resistance compared to DS, while no differences were found between DRC and DR. Thus, in the Dahl rat, hypercholesterolemia alone does not initiate glomerular injury. In this model, hypercholesterolemia is a pathogenetic factor in glomerular injury only when it coexists with systemic hypertension. PMID- 1614040 TI - Modulation of glomerular proteoglycans by insulin-like growth factor-1. AB - Effect of insulin-like growth factor-1 (IGF) on the synthesis of glomerular proteoglycans (PGs) in an ex vivo recirculating organ perfusion system was investigated. Kidneys were perfused with a medium (approximately 80 ml) containing [35S]-sulfate (250 microCi/ml) and IGF (62.5 to 625 ng/ml). After radiolabeling, a small cortical piece was saved for tissue autoradiography, and the remaining kidney and the perfusion medium were utilized for biochemical studies. The glomeruli were isolated; their PGs extracted and characterized. A two- to threefold increase of the total radioactivities in tissue and media fractions was observed with the exposure to IGF. By Sepharose CL-6B chromatography, the tissue PGs eluted as two peaks (A and B) with Kav = 0.24 and 0.48, and the majority of the radioactivity was confined to peak A. This peak contained intact PGs while peak B included glycosaminoglycan (GAG) chains. Elution profiles of the glomerular PGs were similar in the control and IGF groups. However, there was a disproportionate increase of chondroitin/dermatan sulfate in the IGF group. The media fractions also had two peaks, and most of the radioactivity was associated with peak B containing GAG chains. A remarkable accentuation of peak B along with significant increase in the chondroitin/dermatan sulfate were observed in the IGF group. By DEAE-Sephacel chromatography, the PGs/GAGs of IGF group eluted at a relatively lower salt concentration as compared to the control. Autoradiography revealed a relatively high concentration of radioactivity over the mesangium as compared to the other cell types of the glomerulus. [35S]-methionine studies revealed a generalized increase of protein synthesis in the IGF group, but comparatively much less than that of PGs/GAGs. These results indicate that IGF enhances the biosynthesis of PGs/GAGs by various cell types of the renal glomerulus, especially that of the mesangial cell, as reflected by the selective increase of chondroitin/dermatan sulfate. PMID- 1614041 TI - Contrast nephropathy in patients with impaired renal function: high versus low osmolar media. AB - Prescription of low osmolar contrast to prevent nephrotoxicity in subjects with pre-existing renal impairment is costly and has not been clearly shown to be effective. We entered 249 subjects with a pre-contrast serum creatinine greater than 120 mumol/liter (1.35 mg/dl) having cardiac catheterization or intravenous contrast into a randomized controlled trial comparing high and low osmolar contrast. The outcome assessed was a rise in serum creatinine repeated 48 to 72 hours after contrast. A further 117 patients entered the non-randomized prospective arm of the study. In the randomized study the serum creatinine rose by at least 25% after contrast in 8 of 117 (6.8%) given high and in 5 of 132 (3.8%) given low osmolar contrast (P greater than 0.05, one-tailed 95% confidence interval for the difference 3 to 7.8%). More severe renal failure (greater than 50% increase in serum creatinine) after contrast was uncommon (3.4% with high and 1.5% with low osmolar contrast). A rise in serum creatinine after contrast was significantly associated with the severity of the pre-contrast renal impairment and the presence of diabetes mellitus, but not with type of contrast. Diabetics with a serum creatinine greater than 200 mumol/liter (2.25 mg/dl) pre-contrast had a highest risk of deterioration in renal function after contrast. We conclude that in patients with pre-existing renal impairment the incidence of contrast nephropathy was not significantly different comparing high osmolar and nonionic contrast. The potential benefit of nonionic contrast in moderate renal impairment is likely to be small, but trials in diabetics with severe renal impairment should be undertaken urgently. PMID- 1614042 TI - Toxicity of osmotic solutes on human mesothelial cells in vitro. AB - We evaluated the effect of the various osmotic solutes on the growth rate of human mesothelial cells (HMC) in an in vitro culture. Glucose inhibited proliferation of HMC in a dose dependent way. At high glucose concentrations (60 mM, 90 mM) the effect was instant but at lower concentration (30 mM) decrease in the mesothelial cell proliferation was significant only after five days of incubation. Reversibility of the glucose effect was inversely proportional to exposure time to this solute. Mannitol and glycerol studied in similar concentrations as glucose decreased proliferation of the mesothelial cells less than glucose, whereas amino acid glycine had a similar effect to glucose. However, all osmotic solutes caused similar injury to mesothelial cells membrane as measured by release of LDH. These results suggest that the toxic effect of the osmotic solutes on proliferation of the mesothelial cells depends not only on the hyperosmolality but also on some metabolic effect(s). In an in vitro culture, HMC may provide a suitable model for the study of the toxic effect of dialysis fluid on peritoneal mesothelium. PMID- 1614043 TI - Survival as an index of adequacy of dialysis. AB - To examine how patient survival substantiates dialysis adequacy, 20-year actuarial survival experience was calculated for 445 unselected hemodialysis (HD) patients (97 patients accepted on a temporary basis--and usually kept on their regular dialysis scheme--were left out). The dose of dialysis has been the same and unchanged for all patients since beginning: 24 square meter hours of Kiil dialysis (cuprophane) per week with acetate buffered dialysate. KT/V mean (SD) was 1.67 (0.41). Six months after starting dialysis, 98% of patients were normotensive and off all blood pressure (BP) medication. The mean population hematocrit, excluding the only 6 patients receiving erythropoietin supplementation, was 28%. Survival rate was 87% at 5 years, 75% at 10 years, 55% at 15 years, and 43% at 20 years of HD. The satisfactory control of BP without using potentially toxic BP drugs and the higher than usual dose of dialysis are two possible explanations for survival data better than usually reported. We suggest that patient survival should be considered as the best overall index of adequacy of dialysis. PMID- 1614044 TI - Fistula dysfunction: effect on rapid hemodialysis. AB - Rapid hemodialysis (Qb 400 to 500 ml/min) places considerable demands on hemodialysis vascular access. This six-month prospective study enrolled 52 patients and evaluated urea recirculation as a means of detecting fistula dysfunction. It evaluated the effects of fistula location and dialysis blood flow on urea recirculation during rapid hemodialysis and assessed the effect of rapid dialysis on fistula thrombosis. Urea recirculation increased as Qb increased from 300 to 400 ml/min (8 +/- 3% to 16 +/- 3%, P less than 0.05). The extent of urea recirculation was also fistula site dependent (radial fistulas 18 +/- 4%, upper arm fistulas 11 +/- 3%, Qb 400 ml/min, P less than 0.05). Site and blood flow dependent urea recirculations were an indicator of venous stenoses. When venous stenoses were corrected, urea recirculation rates improved (36 +/- 3% to 21 +/- 3%, P less than 0.05). There were no differences between methods of determining urea recirculation early in dialysis (contralateral arm venepuncture vs. stop flow technique; 30 to 60 min). However, at 120 minutes urea recirculation was significantly greater with the contralateral arm venepuncture technique. Venous dialysis pressure at Qb 400 ml/min had limited use as a predictor of venous stenoses unlike its value at lower Qb. Fistula thrombosis (0.26/patient year of dialysis) and fistula replacement (0.09/patient year of dialysis) were similar to our observations in a conventional hemodialysis facility where prospective correction of fistula dysfunction was also used. PMID- 1614045 TI - Renal hemodynamics and reduction of proteinuria by a vasodilating beta blocker versus an ACE inhibitor. AB - The effects of a nonselective beta-adrenergic blocking drug with beta-2 agonist activity (dilevalol 200 mg) on proteinuria and renal hemodynamics were evaluated in a double-blind crossover study versus an ACE inhibitor (enalapril 5 mg) in eight patients with glomerulonephritis, moderate renal function impairment and proteinuria greater than 1 g/24 hr. Patients were studied after a one week placebo phase while off all other medications, except steroids in a few cases, and after three weeks of treatment. A 10-day placebo washout perod was included between the various drug treatments. During each period renal hemodynamics were measured by clearance techniques, and urinary protein excretion as well as fractional clearance of albumin and IgG were determined. Both drugs reduced mean arterial pressure and proteinuria to a similar extent [mean arterial pressure: placebo 108 +/- 13 mm Hg; dilevalol 103 +/- 11 mm Hg (P less than 0.05); enalapril 103 +/- 12 mm Hg (P less than 0.05); protein excretion: placebo 5.1 +/- 4.2 g/day; dilevalol 3.3 +/- 3.0 g/day (P less than 0.05); enalapril 2.8 +/- 2.8 g/day (P less than 0.05)]. The antiproteinuric effect was greater with enalapril than dilevalol. Dilevalol reduced GFR [baseline inulin clearance: 73.3 +/- 38 ml/min/1.73 m2; after dilevalol: 63.3 +/- 28 ml/min/1.73 m2 (P less than 0.05)] and the decrease of proteinuria correlated positively with the reduction of GFR. Enalapril did not significantly lower the GFR (inulin clearance during enalapril 66.8 +/- 23 ml/min/1.73 m2) and the reduction of proteinuria did not correlate with the lowering of the GFR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614046 TI - Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease. AB - Autosomal-dominant polycystic kidney disease results in renal failure at a varying age from childhood to old age. We postulated that factors other than the culprit gene alone contribute to the course of progression of the renal failure. We studied 580 subjects with autosomal-dominant polycystic kidney disease and 194 unaffected family members. We calculated survival curves to end-stage renal failure or death and developed a linear model for testing the effects of single or multiple variables on the progression of renal failure as estimated from the reciprocal of serum creatinine. Fifty-two subjects died and 94 reached end-stage renal failure during the period of observation, yielding functional survivals of 71% at age 50 years, 53% at 58 years and 23% at 70 years. The following variables were independently associated with worse mean renal function at a given age (P value less than 0.01): the PKD1 gene, younger age at diagnosis, male gender, hypertension, increased left ventricular mass, hepatic cysts in women, three or more pregnancies, gross hematuria, urinary tract infections in men and renal size expressed as renal volume. The following were not associated significantly with the course of renal function: gender of affected parent, mitral valve prolapse, intracranial aneurysms, any pregnancy, hepatic cysts in men and urinary tract infections in women. The identification of unalterable maleficent factors such as the PKD1 gene and male gender permit more informed counseling while the identification of alterable factors such as hypertension, number of pregnancies and recurrent urinary tract infections provides the clinician with the opportunity to modify these factors and improve the management of patients with autosomal-dominant polycystic kidney disease. PMID- 1614047 TI - A quantitative description of solute and fluid transport during peritoneal dialysis. AB - To investigate the relationship between dialysate glucose concentration and peritoneal fluid and solute transport parameters, 41 six-hour single dwell studies with standard glucose-based dialysis fluids containing 1.36% (N = 9), 2.27% (N = 9) and 3.86% (N = 23) anhydrous glucose were carried out in 33 clinically-stable continuous ambulatory peritoneal dialysis (CAPD) patients. Intraperitoneal dialysate volumes (VD) were determined from the dilution of 131I albumin with a correction applied for its elimination from the peritoneal cavity (KE, ml/min). Diffusive mass transport coefficients (KBD) were calculated from aqueous solute concentrations (with a correction applied for the plasma protein concentration and, for electrolytes, also for the Donnan factor) during a period of dialysate isovolemia. The intraperitoneal amount calculated to be transported by diffusion was subtracted from the measured total amount of solutes in the dialysate, yielding an estimate of non-diffusive solute transport. The intraperitoneal dialysate volume over time curve was characterized by: initial net ultrafiltration (lasting on average 92 min, 160 min and 197 min and with maximum mean net ultrafiltration rates 6 ml/min, 8 ml/min and 14 ml/min, respectively, for the 1.36%, 2.27% and 3.86% solutions); dialysate isovolemia (lasting about 120 min for all three solutions) and fluid reabsorption (rate about 1 ml/min for all three solutions). KBD for glucose, potassium, creatinine, urea and total protein did not differ between the three solutions and the fractional absorption of glucose was almost identical for the three glucose solutions, indicating that the diffusive transport properties of the peritoneum is not influenced by the initial concentration of glucose or the ultrafiltration flow rate. About 50% of the total absorption of glucose occurred during the first 90 minutes of the dwell. The mean percentage of the initial amount of glucose which had been absorbed (%GA) at time t during the dwell could be described (r = 0.999) for all three solutions using the experimental formula %GA = 85 - 75.7 * e 0.005*t. After 360 minutes, about 75% of the initial intraperitoneal glucose amount had been absorbed corresponding to a mean (+/- SD) energy supply of 75 +/- 6 kcal, 131 +/- 18 kcal and 211 +/- 26 kcal for the three solutions. Non diffusive (that is, mainly convective) transport was almost negligible for the less hypertonic solutions while it was estimated to account for 30 to 40% of the total peritoneal transport of urea, creatinine and potassium during the first 60 minutes of the 3.86% exchange. PMID- 1614048 TI - Effect of fluoride on aluminum-induced bone disease in rats with renal failure. AB - Aluminum (Al) accumulation in renal failure is an etiological factor in the pathogenesis of low turnover bone disease. Aluminum-induced impairment of mineralization has been related to a reduced extent of active bone-forming surface. The present study investigated the effect of fluoride, a potent stimulator of osteoblast number, on the toxicity of aluminum in rats with renal failure (Nx). Following a large parenteral aluminum load (3.2 mg/kg x day) over a period of nine weeks, bone histomorphometry of vertebral cancellous bone revealed a severe low-turnover osteodystrophy as evidenced by a fall in osteoblastic osteoid surfaces and mineral apposition rates. Concurrent administration of fluoride [20 mg/liter (F20) or 40 mg/liter (F40) supplied with the drinking water] resulted in a significant increase in the number of osteoblasts (Nx+Al+F40 vs. Nx+Al, 33.75 +/- 2.83 vs. 1.81 +/- 0.43 mm-1, P less than 0.001) together with an overall reduced deposition of aluminum in bone (469.3 +/- 24.6 vs. 592.2 +/- 28.3 micrograms/g, P less than 0.01). However, there was an increase in the fraction of osteoid surface exhibiting stainable aluminum at the bone-osteoid interface (70.7 +/- 7.1 vs. 44.3 +/- 6.0%, P less than 0.005). Fluoride-exposed rats accumulated a significantly larger osteoid volume, suggesting an exacerbation of the osteomalacic lesion, and furthermore, dynamic histomorphometric parameters remained depressed. These results indicate that fluoride has a distinct effect on the pattern of aluminum deposition in bone. In addition, fluoride antagonizes the aluminum-induced reduction in osteoblast number but provides no amelioration of the impaired mineralization in aluminum intoxicated rats. Thus, in this model a decrease in the extent of osteoblast surface does not account for the development of aluminum-related bone disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614049 TI - Single kidney function: early and late changes in urate transport after nephrectomy. AB - Renal urate transport was studied by means of pyrazinamide (PZA) and probenecid (PB): (a) before and at 2, 6, 24 weeks (24 patients), (b) 1 to 30 years after uninephrectomy in 27 and 12 patients with Ccr greater than 80 and 30 to 70 ml/min, respectively. Uninephrectomy was followed by important tubular urate transport modifications during at least two weeks, which lead to a marked uricosuria as indicated by significant increase in FEur (mean value +/- SD, 0.228 +/- 0.059 vs. 0.097 +/- 0.014 and 0.099 +/- 0.019 in normals and chronically diseased solitary kidneys). Reduced response to PZA and PB suggests a diminished reabsorptive capacity for urate mainly at the presecretory site which persisted after FENa normalization. Tubular compensations were presumably complete at six weeks, since pattern of urate transport returned to normal with an almost complete reabsorption of filtered urate load (99%) and a percentage of postsecretory reabsorption (80%) very close to those seen in normal subjects with a pair of kidneys. The adjustment in urate excretion in solitary kidneys was achieved by a significant increase of secreted urate as compared with 50% of pre uninephrectomy values. Thus, increased urate secretion by the remaining intact organ is sufficient to maintain urate balance with a normal serum level. PMID- 1614050 TI - The pathobiology of subclinical pyelonephritis--an experimental evaluation. AB - Clinical studies have demonstrated a poor correlation between localization tests, which are designed to determine the site of urinary tract infection, and symptoms of upper urinary tract infection. One explanation is that microorganisms may be present in the kidney but not initiate an inflammatory response with associated symptoms. An animal model has been developed to obtain quantitative information on the comparative pathobiology of lesion-inducing and non-lesion-inducing infections. In this model, non-manipulated kidneys had acquired a persistent microbial flora within 48 hours of the lower urinary tract becoming infected. This bacterial invasion was not associated with gross or histologic changes within the renal parenchyma, but minor foci of inflammatory cells were seen beneath the epithelium lining the calyces. Ureteric urines from such kidneys contained many leukocytes and high numbers of bacteria. These results showed that the kidneys were infected, rather than colonized, and the term "subclinical" infection was appropriate. Antimicrobial agents were variably successful at eradicating the infection. These experimental observations support the concept of subclinical pyelonephritis and may explain the absence of symptoms in the clinically equivalent situation in humans. PMID- 1614051 TI - A model of the volumetrically-controlled hemodialysis circuit. AB - We developed a model that predicts the hemodynamics of the volumetrically controlled circuit used to administer high flux hemodialysis. The equations simulate the entire blood side of the circuit so that blood and dialysate pressures can be predicted from a knowledge of circuit component and patient characteristics. An alternative method of computation has also been devised which permits measured circuit pressures to be used to predict patient blood access pressure, dialyzer resistance to flow and membrane hydraulic conductivity. Success of the model was evaluated by measuring both circuit pressure and component characteristics. The model successfully predicted circuit pressures when measured component characteristics were employed as model inputs. Conversely, the model accurately predicted circuit component characteristics when measured pressures were employed as inputs (8 patients, 30 dialyses). Specific predictions of the model include the following. Elevations of patient blood access pressure will cause blood and dialysate pressures to rise equivalently without affecting the rate of back-filtration or location of pressure equilibrium along the dialyzer axis. Elevated hematocrit is predicted to increase circuit pressures to a degree that is similar to a poorly functioning blood access, however, high hematocrit markedly augments back-filtration and moves the point of pressure equilibrium toward the dialyzer entrance. We conclude that the model provides a predictive tool that can be used to optimize circuit design. Alternatively, the model can be used to separate the influence of a poorly functioning patient access from other factors which can elevate circuit pressures. PMID- 1614052 TI - Non-invasive prediction of aluminum bone disease in hemo- and peritoneal dialysis patients. AB - Between October 1987 and October of 1989, we conducted a prospective study to evaluate non-invasive test strategies for predicting aluminum bone disease (ABD) in a group of largely unselected dialysis patients based on their deferoxamine (DFO) test alone, or the combined results of their DFO test and intact 1-84 parathyroid hormone (PTH) levels. These test parameters were evaluated against the pathological diagnosis of ABD based on bone biopsy ("gold standard"). A total of 445 patients in three dialysis centers in Toronto were serially followed for their clinical, laboratory and risk parameters for renal osteodystrophy during the study, and 259 (142 PD and 117 HD) patients underwent a series of investigations which included the DFO test, measurement of intact 1-84 PTH levels, and an iliac crest bone biopsy. Serum aluminum ([Al]) level greater than or equal to 3700 nM (or 100 micrograms/liter) had a positive predictive value (PPV) of 75% for ABD in our PD and 88% in our HD patients, but its sensitivity was low (10 and 37%). Delta [Al] (that is, incremental rise of serum [Al] from baseline post-DFO) was useful in predicting ABD in our PD but not HD patients. Test combination based on delta [Al] greater than or equal to 5550 nM (or 150 microgram/liter) and PTH levels less than 20 pM (or 200 pg/ml) yielded the best PPV greater than or equal to 95% for ABD in both PD and HD patients. This test cut-off would remain highly predictive of ABD even if the prevalence of ABD decreases to as low as 5% for the PD patients and 10% for the HD patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614053 TI - A new scintigraphic method to characterize ultrafiltration in hollow fiber dialyzers. AB - Ultrafiltration and pressure profiles in hollow fiber dialyzers with different hydraulic permeabilities have been investigated with a new scintigraphic method. Radiolabelled albumin macroaggregates, used as a nondiffusible marker molecule, were added to the blood in an in vitro circuit and circulated through cuprophan and polysulphon dialyzers. Since the marker molecule was too big to cross the dialysis membrane, its changes in concentration were assumed to occur in response to the variation of the blood water content (filtration or back-filtration). These changes in concentration, recorded by a gamma camera, were evaluated to establish the cumulative values of filtration and back-filtration and their relevant profiles along the length of the dialyzer. The achieved data were compared with the experimental values of ultrafiltration empirically measured and with the theoretical values predicted by a classic linear method. Two conditions were analyzed: A) the minimal filtration rate necessary to avoid back-filtration (critical filtration); and B) the condition of zero net filtration in which filtration equals back-filtration. The nuclear method proved to be extremely precise in predicting the ultrafiltration values and significantly more precise than the linear method, especially for the highly permeable dialyzer. The reason for that probably depends on the non-linear pressure and ultrafiltration profile observed with the scintigraphic pattern of the dialyzer. Viscosity changes and local variations in blood flow may in fact interfere with the pressure drop inside the hollow fibers and result in such a complex behavior. The other interesting aspect of this method is the possibility of accurate measurement of the amount of back-filtration that wouldn't be possible with simple calculations. In conclusion, the complex nature of the phenomena regulating the water fluxes in hollow fiber dialyzers requires more complex calculation than a simple linear model to achieve an accurate range of predictability. PMID- 1614054 TI - Lipoprotein abnormalities in hyperlipidemic and normolipidemic men on hemodialysis with chronic renal failure. AB - Lipids, lipoproteins, apolipoproteins (apo) and apo E polymorphism were determined in 101 men with chronic renal failure (CRF) were were on hemodialysis and 101 healthy controls matched for age and sex. Patients with CRF on hemodialysis had significantly higher levels of serum triglycerides, very-low density lipoprotein (VLDL) cholesterol, intermediate-density lipoproteins (IDL), and lower levels of low- and high-density lipoproteins (LDL and HDL, respectively) than controls. Regarding apolipoproteins, serum apo B concentrations were decreased. Apo C-III concentrations in sera and in VLDL and HDL fractions were significantly increased in 35 hemodialysis patients compared with 32 controls. Seventy-eight of the 101 CRF patients had normal serum cholesterol and triglycerides (less than 5.2 mmol/liter and less than 2.3 mmol/liter, respectively). However, this subgroup also showed a significant increase in VLDL-triglycerides and serum apo E concentration in addition to changes observed in the group as a whole. Apo E polymorphism in our study population did not differ from that reported for other European populations. According to the different apo E phenotypes, lipids and lipoprotein composition showed no significant differences in controls or patients. We conclude that accumulation of triglyceride-rich lipoproteins in patients with CRF on hemodialysis may thus be at least in part related to the enrichment of apo C-III in VLDL and HDL fractions. Lipoprotein profile in hemodialysis patients, including those with normal serum cholesterol and triglyceride levels, is consistent with high cardiovascular risk. PMID- 1614055 TI - Removal of aluminoxamine and ferrioxamine by charcoal hemoperfusion and hemodialysis. AB - We studied the removal of aluminoxamine (AlO) and ferrioxamine (FO) by (i) hemoperfusion/hemodialysis using an AluKart in combination with either a Cuprophan F-120 or a Hemophan FH-160 membrane, or (ii) hemodialysis with a high flux F-60 polysulfone membrane. The same six dialysis patients underwent in a random order dialysis by the three set-ups after i.v. infusion of 30 mg/kg of desferrioxamine (DFO) during the last half an hour of the preceding dialysis session. The mean +/- SD plasma AlO and FO clearances of the AluKart combined with either a F-120 or FH-160 membrane were 194.3 +/- 25.8 ml/min (AlO) and 164.2 +/- 41.3 ml (FO) at the start of dialysis declining to respectively 76.6 +/- 27.3 and 68.5 +/- 42.6 ml/min at the end of dialysis. With a high-flux dialysis membrane the intra-dialytic plasma clearance remained constant at 81.5 +/- 6.8 ml/min for AlO and 60.0 +/- 2.8 ml/min for FO. In the presence of an AluKart combined with a FH-160 up to 84 +/- 27% and 84 +/- 19% of the available AlO and FO could be removed during a four-hour hemoperfusion/hemodialysis session. During the first hour of dialysis, respectively 59 and 58% of the total amount of AlO and FO extracted by the AluKart was removed compared to only 9 and 16% during the last hour.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614056 TI - Radiocontrast-induced nephropathy in humans: role of renal vasoconstriction. AB - Radiocontrast-induced nephropathy (RCIN) is a common cause of acute renal failure in hospitalized patients. Renal vasoconstriction figures prominently in the proposed pathogenesis of RCIN based on animal experiments. Prior human studies examining renal hemodynamic changes after contrast medium (CM) injection are inconclusive. No previous study of animals or humans has established a relationship between CM-associated renal hemodynamic changes and the subsequent development of RCIN. In the present study, we examined the renal hemodynamic effects of CM in patients at high risk of RCIN. In addition, we related those effects to the subsequent development of RCIN. Using renal vein thermodilution catheters, we measured renal blood flow (RBF) in 12 patients with chronic renal failure [serum creatinine (SCr) greater than or equal to 159 mumol/liter] during ionic CM injection for cardiac catheterization. We made measurements at the start of the procedure (t = 0), before the ventriculogram (t = 5), after the ventriculogram (t = 15), and after the coronary angiogram (t = 65). We measured SCr at t = 0 and again 24 and 48 hours later. Mean RBF for the group tended to increase after the ventriculogram, and increased significantly by t = 65 (P less than 0.005 vs. t = 0). When examined by individual patient, RBF fell below baseline in three patients (30%) at t = 15, but rose above baseline again by t = 65. Only one patient (8.3%) had a fall in RBF below baseline at t = 65. RCIN (defined as an increase in SCr greater than or equal to 25% above baseline) developed in six patients (50%) within 48 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614057 TI - Dialysis-related amyloidosis. PMID- 1614058 TI - Effects of chronic felodipine treatment on renal function and morphology in SHR. AB - To investigate if blood pressure reduction per se may prevent progressive renal disease in aging spontaneously hypertensive rats (SHR), 15-month-old SHR were treated with the calcium antagonist felodipine, with the beta-blocker metoprolol or with the combination for six months. The combined regimen caused the greatest blood pressure reduction over time, metoprolol caused the least, while felodipine had an intermediate effect. At the end of treatment, urinary protein excretion and endogenous creatinine clearance were determined in rats kept in individual metabolic cages. At autopsy, the kidneys were histologically examined and indices of chronic progressive nephrosis and glomerular sclerosis were determined. A positive correlation was found between urinary protein excretion and glomerular sclerosis. Glomerular sclerosis was low in the groups of rats with high endogenous creatinine clearance. In both groups treated with felodipine, glomerular sclerosis and urinary protein excretion were significantly reduced compared to untreated controls. These results illustrate that the calcium antagonist felodipine attenuates proteinuria and glomerular sclerosis in aging SHR. The blood pressure reduction may be of major importance in this respect, although a direct action on the sclerotic process within the glomeruli may also contribute. PMID- 1614059 TI - Acute renal effects of felodipine in hypertensive patients with kidney disease. AB - In contrast to other types of directly acting vasodilators, calcium antagonists promote sodium excretion. It is not well established, however, whether these drugs also induce natriuresis in hypertensive patients with renal disease. Therefore, we studied the acute effects of the dihydropyridine calcium antagonist felodipine in nine such patients (CCr 68 +/- 19 ml/min) and 12 healthy normotensive subjects. In both the hypertensive patients and the normotensive subjects total and fractional sodium excretion rose during the first 40 minutes of intravenous felodipine infusion; in the hypertensive patients this rise of sodium excretion was positively correlated to the initial glomerular filtration rate (GFR) (r = 0.87, P less than 0.01). In the patients, during ongoing felodipine infusion, natriuresis was attenuated in the setting of a large continuing decrease of blood pressure. In contrast, in the normotensive subjects, in whom blood pressure did not fall any further, a steady rise of sodium excretion was observed. In both the hypertensive patients and the normotensive subjects GFR remained unchanged and renal vascular resistance decreased, whereas renal plasma flow increased only in the latter group. Changes in sodium excretion were not correlated to changes in renal hemodynamic parameters. It is concluded, that also in hypertensive patients with diminished renal function felodipine exerts a potentially advantageous natriuretic effect. However, this natriuretic effect is possibly less at lower GFR and seems to be attenuated by blood pressure reduction. The mechanism of this natriuretic effect as well as its contribution to the antihypertensive effect of felodipine still has to be clarified. PMID- 1614060 TI - Long-term effects of felodipine in patients with reduced renal function. AB - To characterize the long-term effects of calcium antagonists on renal function in hypertension felodipine was used to treat 14 patients with severe uncontrolled hypertension associated with renal functional impairment: six patients had renal parenchymal hypertension, six had essential hypertension and two had renovascular hypertension. Mean blood pressure was 197 +/- 2/115 +/- 3 mm Hg despite treatment with three or more antihypertensive drugs. Mean glomerular filtration rate (GFR) was 39 +/- 6 ml/min (Cr-EDTA clearance) before initiation of felodipine treatment. All patients experienced a blood pressure reduction after starting felodipine treatment, which persisted during long-term therapy in combination with previous medication except former vasodilating drugs. Blood pressure after 12 and 24 months was 152 +/- 7/89 +/- 2 and 157 +/- 5/90 +/- 2 mm Hg, respectively. Patients with moderately impaired GFR and absence of progressive renal disease (N = 8) manifested an increase in GFR after 6 and 12 months on felodipine (59 +/- 10 to 63 +/- 7 and 70 +/- 6 ml/min, respectively, P less than 0.05). Renal plasma flow (PAH clearance) exhibited only a slight increase (315 +/ 68 to 340 +/- 63 and 314 +/- 69 ml/min) with a consequent increase in filtration fraction (18 +/- 1 to 21 +/- 1 and 20 +/- 1%, NS). At follow-up after six to eight years patients with initial GFR greater than or equal to 50 ml/min had a maintained renal function. In five patients a progressive deterioration of renal function had been documented.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614061 TI - Are calcium antagonists of value in ameliorating the course of chronic renal disease? AB - Renal protection is defined as an attenuation or significant slowing of the irrevocable decrease in renal function over time, which occurs subsequent to renal dysfunction. Control of systemic hypertension by whatever means exerts a renal protective effect. Evidence suggesting a specific action of individual antihypertensive agents is less certain. Calcium antagonists may exert a specific renal protective effect. Experiments in rats with reduced renal mass, desoxycorticosterone-induced hypertension, chronic angiotensin II infusion, and in spontaneously hypertensive rats support such a view. In three crossover trials, calcium antagonists reduced proteinuria in patients with type 2 diabetes mellitus. Preliminary data from a single prospective trial in patients with renal insufficiency offer additional support; however, definitive conclusions cannot be reached without further trials. In particular, comparative trials of different classes of antihypertensive agents with equal blood pressure control are needed. Thus far, only reducing systemic blood pressure per se has been shown to be of value in attenuating hypertension-induced renal dysfunction in humans. PMID- 1614062 TI - Growth factors and glomerular sclerosis. AB - Progress has been made over the last decade in our understanding of the pathophysiology of progressive chronic renal failure (CRF) and the underlying glomerular sclerosis. Although these advances have been made in experimental animals and have so far had little impact on the management of CRF in humans, they nevertheless identify pathways through which glomerular sclerosis takes place. They also identify the cells involved in this process and the role of cytokines/growth-promoting peptides in the communication between these cells. It is the purpose of this review to detail the contribution of cytokines to glomerular scarring. PMID- 1614063 TI - Role of calcium in the progression of renal disease: experimental evidence. AB - Intracellular calcium mediates a wide array of cell functions in mesenchymal as well as in epithelial and endothelial cells. These comprise regulation of vascular tone, cell proliferation and synthesis of prostanoids and cytokines. Therefore, it is not surprising that a substantial body of evidence has emerged to suggest a crucial role of calcium in the initiation and perpetuation of renal disease. Increased deposition of calcium was found in the renal cortex of rats with remnant kidney and in kidney tissue of patients with end-stage renal failure. Calcium plays an important role in altered intrarenal and glomerular hemodynamics with increased glomerular wall tension as well as in cellular proliferation and in recurrent ischemic events leading to glomerulosclerosis and interstitial fibrosis. Besides hemodynamic mechanisms, additional calcium dependent mechanisms must be considered for glomerular hypertrophy and/or mesangial proliferation to develop, namely the role of growth factors, prostanoids and cytokines. Their signals include receptor-regulated production of inositol-trisphosphate and diacylglycerol and the consecutive stimulation of protein kinase C and the Na/H-antiport. Full activation of this antiport, which raises intracellular pH and thereby stimulates protooncogenes, again requires the presence of calcium. Recurrent focal glomerular ischemia may result in cellular and mitochondrial calcium overload that may interfere with cellular energy metabolism. Calcium also activates proteinases and the production of oxidants to enhance neutrophil-mediated cell injury. These deleterious effects of calcium may initiate and perpetuate the progression of renal disease and eventually lead to end-stage renal failure. PMID- 1614064 TI - Means of clinical evaluation of renal disease progression. PMID- 1614065 TI - Does essential hypertension cause end-stage renal disease? AB - The number of patients developing end-stage renal disease (ESRD) as a consequence of hypertension is increasing and accounts for 25% of new cases of ESRD in the United States. However, the diagnosis of hypertensive ESRD is one of exclusion and no pathologic data corroborate this classification. Undoubtedly, these patients suffer from a variety of diseases, including accelerated hypertension and atherosclerotic disease of the large arteries. Also included are patients with an undiagnosed primary renal disease. The prevalence of these conditions in the hypertensive population is unknown. It is also proposed that mild to moderate hypertension can lead to ESRD. In support of this view, early investigators noted that nephrosclerosis was correlated with hypertension and/or left ventricular hypertrophy. More recently, in the Hypertension Detection and Follow-up Program, renal function was found to decline in some patients despite treatment. Data from the Baltimore Longitudinal Study of Aging indicate that the rate at which creatinine clearance declines with aging is correlated with blood pressure. A recent retrospective study reported that serum creatinine increased significantly in approximately 15% of treated hypertensive patients. However, in none of these studies was the presence of intrinsic renal disease definitively excluded. Furthermore, although an increase in serum creatinine or decline in clearance has been reported, progression to end-stage renal disease has not been documented. Therefore, additional studies are necessary to determine the frequency with which essential hypertension leads to end-stage renal disease. PMID- 1614066 TI - Determinants of progressive renal disease in diabetes mellitus. AB - The prognosis for the patient with diabetic nephropathy has improved considerably during the last decade. This is due to identification and treatment of different risk factors. Elevated blood pressure has turned out to be a major risk factor in established diabetic nephropathy. The impact of metabolic control has also been demonstrated. Lipid abnormalities have recently been identified as a possible factor that accelerates loss of renal function. The role of renal hemodynamic alterations is probably also important. Their contribution can indirectly be assessed by studying the effects of pharmacologic therapy. Angiotension converting enzyme inhibitors reduce proteinuria by a mechanism independent of systemic blood pressure and there is suggestive evidence that they preserve renal function to a greater degree than other antihypertensive agents. PMID- 1614067 TI - Effects of calcium antagonists on renal hemodynamics and glomerular function. AB - Cytosolic [Ca2+] can be increased by influx of the ion from the extracellular compartment, Ca2+ release from intracellular storage sites, and/or a reduced activity of active transport processes for Ca2+ extrusion or sequestration. Organic calcium antagonists block transmembrane calcium entry and, therefore, can be utilized to evaluate the importance of calcium influx in the regulation of renal hemodynamics. Recent studies indicate that calcium antagonists selectively vasodilate preglomerular arterioles, leading to increases in renal blood flow (RBF), glomerular filtration rate (GFR) and glomerular pressure. In contrast with angiotensin converting enzyme inhibitors and other vasodilator agents, calcium antagonists primarily influence the component of renal vascular resistance responsible for autoregulation, potently attenuating autoregulatory efficiency. Calcium antagonists also block the afferent arteriolar vasoconstriction elicited by angiotensin II, while not influencing the efferent arteriolar vasoconstriction evoked by this peptide. Tubuloglomerular feedback (TGF)-mediated vasoconstrictor responses are also abolished by calcium antagonists, indicating that the TGF effector mechanism may require transmembrane calcium influx into the smooth muscle cells of the afferent arterioles. These observations provide compelling evidence that calcium influx, through pathways which are influenced by organic calcium antagonists, is an integral component of the afferent arteriolar vasoconstriction elicited by a variety of stimuli, while efferent arteriolar vasoconstriction appears to depend on other calcium access pathways. PMID- 1614068 TI - Renal tubular effects of calcium antagonists. AB - Calcium channel blockers have diuretic and natriuretic properties in normal animals and humans. The renal mechanism by which this natriuresis is produced has not yet been completely defined although dihydropyridine derivatives evoke it in experimental animals independently of any effects on renal blood flow or on the glomerular filtration rate. Injections or infusions into the renal artery indicate that the renal excretory effect is secondary to a direct action on renal tubular water and solute reabsorption but not to renal hemodynamic changes. Studies undertaken to localize the site of action of dihydropyridine calcium antagonists on renal tubules by renal clearance and micropuncture techniques suggest that both proximal and distal tubular sites are involved. Primary sites of action in distal convoluted tubules and in the collecting duct have been identified for felodipine and nisoldipine during sodium infusion, whereas sites for nitrendipine in proximal tubules have been demonstrated in strict hydropenia. Both changes in the tubuloglomerular feedback setting and suppression of aldosterone secretion have been proposed to explain some of these effects. The changes do not, however, seem to be dependent on renal innervation. In normal humans, the degree and duration of natriuresis and diuresis correlate with the dose of dihydropyridine derivatives and the extent of systemic pressure reduction. Clearance studies of normal subjects indicate an effect of different dihydropyridine derivatives on tubular fluid and electrolyte reabsorption. Nicardipine and nifedipine are reported to exert proximal tubular actions based either on urate and phosphate excretion or water and lithium clearance. The measurement of tubular indices following felodipine administration suggests a proximal tubular site of action.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614069 TI - Renal effects of felodipine--a review. AB - Felodipine is a dihydropyridine calcium antagonist which lowers total peripheral resistance and blood pressure in doses which have no effect on cardiac conduction and contractility. It increases the urinary excretion of sodium and water due to decreased renal tubular reabsorption from the glomerular ultrafiltrate. This is observed at low doses which do not affect blood pressure, renal blood flow (RBF) or glomerular filtration rate (GFR). Felodipine decreases total renal vascular resistance and causes a transient increase in RBF in patients with normal RBF. In patients with low pretreatment values, RBF is increased during chronic treatment. Felodipine does not affect normal GFR. Thus filtration fraction may decrease. In patients with severe hypertension and reduced GFR, felodipine treatment results in good blood pressure control and increased GFR. In animal models of progressive renal disease due to hyperfiltration, felodipine has no negative effect on GFR, glomerulosclerosis or survival although proteinuria may increase. In salt sensitive rats given high salt diet, resulting in hypertension, hypoperfused kidneys and progressive renal damage, felodipine treatment results in reduced blood pressure, increased RBF and GFR, and reduced proteinuria and glomerulosclerosis. In patients with previously refractory hypertension and progressive impairment of renal function, felodipine treatment results in good blood pressure control and a reduced rate of progression. In animals, felodipine limits the extent of renal damage after ischemia and reperfusion. PMID- 1614070 TI - Progression of renal disease: current concepts and therapeutic approaches. AB - The pathogenesis of progressive renal disease includes systemic hypertension and intrarenal factors that may be hemodynamic or metabolic in origin and involve mediators of inflammation. Most current information derives from experiments in rodents. In other species (rabbit, dog, baboon) subjected to renal mass reduction, a greater variety of pathologic changes is apparent than in rats. Clinical trials at controlling progression of renal disease are compounded by numerous factors; and it is not evident that extrapolation can safely be made from results of animal studies to human disease. The mechanism(s) of renal disease progression in humans, therefore, remain largely unknown. Current therapeutic recommendations in patients with chronic renal disease include limitation of phosphorus absorption, correction of lipid abnormalities and control of systemic blood pressure. The latter can be achieved with a variety of agents some of which, like angiotensin converting enzyme inhibitors and calcium antagonists, may be preferred because of specific intrarenal effects. PMID- 1614071 TI - Calcium antagonists and the kidney: implications for renal protection. AB - During the past decade, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit consistent actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they do dramatically alter the response of this preparation to vasoconstrictor agents. Our recent studies using the isolated perfused hydronephrotic rat kidney model, which permits direct visualization of afferent and efferent arterioles, have demonstrated that the preferential augmentation of glomerular filtration rate observed in the isolated perfused kidney is attributable to preferential vasodilatation of preglomerular vessels. Although the clinical implications of such observations have not been fully delineated, the results of recent studies indicate that calcium antagonists exert salutary effects on renal function in patients with impaired renal hemodynamics. Such disorders include radiocontrast-induced nephrotoxicity and transplant-associated acute renal insufficiency. It is apparent, however, that the effects of calcium antagonists on renal blood flow commend their use in the management of essential hypertension. PMID- 1614072 TI - Hemodynamic comparisons of enalapril and felodipine and their combination. AB - Thirty-six patients (33 male, 3 female) with a mean age of 67 years and a diastolic blood pressure between 95 and 115 mm Hg, after a four-week placebo run in period entered a double-blind crossover study comparing felodipine 5 and 10 mg with enalapril 5 and 10 mg and their combination (enalapril 5 mg + felodipine 5 mg). Combined therapy caused a fall in blood pressure of 24/16 mm Hg at trough level that was greater than the falls with the higher doses of monotherapy. The fall with felodipine was greater than with enalapril. Similar patients responded to felodipine and enalapril but more patients achieved blood pressure control with felodipine. When patients not controlled with enalapril 5 mg had felodipine 5 mg or enalapril 5 mg added, felodipine was more effective at lowering blood pressure than the increase in enalapril dosage. A similar effect occurred in those not controlled with felodipine 5 mg. Adverse effects occurred in 22 patients on felodipine, 14 patients on enalapril and 8 on combined therapy. The lipoprotein profile was not altered significantly. Glomerular filtration rates as assessed by 24-hour creatinine clearance were 90 ml/min at randomization, 125 ml/min on felodipine, 108 ml/min on enalapril and 120 ml/min on the combination. Felodipine and enalapril in low doses are effective antihypertensive agents in elderly people. Felodipine monotherapy is more effective than enalapril monotherapy but a greater blood pressure lowering effect can be obtained with the combination of low doses of enalapril and felodipine. This has the advantage that the number of side effects is less. PMID- 1614073 TI - Glomerular hemodynamics in progressive renal disease. AB - A descriptive survey of renal hemodynamics in the major experimental models of progressive renal disorders (primary loss of renal tissue, primary glomerular injury and primary hypertension) is given. Although the pathogenesis in the different models differs in several respects, increases in glomerular capillary pressure and renal growth factors are important for the development of progressive renal disorders. In primary glomerular disorders, interstitial immune reactions seem to be critical. In glomerular nephritis with increased capillary wall thickness, the increase in glomerular capillary pressure may be of less importance than in other models. A third important factor for progression of renal disorders is a gradual breakdown of autoregulation of renal blood flow and glomerular filtration rate exposing the glomerulus to the variations in systemic blood pressure. PMID- 1614074 TI - Interaction between cyclosporine and felodipine in renal transplant recipients. AB - The nephrotoxic adverse effect of cyclosporine in renal transplantation may be counteracted by calcium antagonists. The effect of a single oral dose of 10 mg of the calcium antagonist felodipine or placebo was studied in ten cyclosporine treated renal transplant recipients before, during, and after an acute intravenous infusion of cyclosporine in a randomized, single-blind crossover study. Glomerular filtration rate, and renal plasma flow, and tubular function evaluated by the lithium clearance technique were determined. Both glomerular filtration rate, renal plasma flow, urinary sodium excretion, fractional excretion of sodium, and lithium clearance increased after felodipine, whereas proximal and distal fractional reabsorption and blood pressure were reduced. Intravenous infusion of cyclosporine per se did not influence any of the parameters. It is concluded that a single dose of felodipine in cyclosporine treated renal transplant recipients has beneficial effects on renal hemodynamics, tubular function and blood pressure. It is suggested that these effects result from a direct vasodilatation and an effect on tubular function, and that felodipine given intravenously seems to antagonize at least some of the nephrotoxic effects of cyclosporine. PMID- 1614075 TI - Evaluation of the efficacy of felodipine in two models of acute renal failure in dogs. AB - Acute renal failure was induced in pentobarbital anesthetized dogs either by withdrawal of the blood and/or by acute renal artery occlusion and efficacy of felodipine in preserving renal function was evaluated. In Wiggers' model of hemorrhagic shock, animals were allowed to bleed into a reservoir and after maintaining a hypotensive state (40-45 mm Hg) for 150 minutes, blood was reinfused and recovery in the renal function was evaluated. In a separate series, a renal artery was completely occluded for 45 minutes and after release of the occlusion recoveries in various markers of renal function were monitored. Felodipine 0.01 mumol/kg i.v. or the vehicle was administered ten minutes before hemorrhage or ten minutes prior to initiation of renal artery occlusion. Comparison of the data between the vehicle-treated dogs from the two models show that although renal blood flow (RBF) was restored to similar levels, recoveries in glomerular filtration rate (GFR), urine volume (UV), urinary excretion of sodium (UNa V) and potassium (UK V) were severely depressed in shock model (15 to 25% of the basal value) and consistently lower than the recoveries in the renal artery occlusion model (30-50%). These data could suggest that the extent of renal impairment is more severe in hemorrhagic shock. Nevertheless, felodipine pretreatment provided significant protection to renal function from ischemic damage in both the models; the drug-treated groups were characterized by significant recoveries in GFR, UNa V and UK V (60-100%) and by prompt and full restoration of RBF and UV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614076 TI - [Neonatal BCG vaccination: as a routine measure or only in special indications?]. PMID- 1614077 TI - [Severe gastroenteritis after HiB preventive vaccination?]. PMID- 1614079 TI - [Legal liability problems of the physician]. PMID- 1614078 TI - [Simultaneous infection with Borrelia burgdorferi--FSME virus]. PMID- 1614080 TI - [The physician as an accident witness: emergency treatment and the problem of failure to treat]. AB - As a witness of an accident the physician has always the duty to render first aid. At least he has to examine carefully whether his help is not or no more necessary. On account of his professional abilities the duty to first aid may concern him as the only person also among several participants, and he must always care to take the best possible measures for the prevention of dangers. In the other case he exposes himself the danger of culpability for not having performed first aid. Apart from a penal verdict also the possibility of a verdict by a professional court of justice for the same offence can be added. In the process before the professional court of justice is examined, whether or not the physician failed in his professional duty to protect and restore health as well as to reduce complaints (section 1, number 2 MBO). PMID- 1614081 TI - [Mucoviscidosis in adulthood. An overview of the research on the psychosocial aspects]. AB - Cystic fibrosis patients do have fairly improved life-expectancies today. Therefore, they are confronted with the obstacles and stresses of adult life. The author reviews studies concerning the following aspects of adult cf-patients: psychosocial functioning, separation from home, coping and compliance. Finally, beneficial modes of psychosocial interventions are discussed. PMID- 1614082 TI - [Homosexuality in childhood and adolescence]. AB - Every second homosexual man has a presentiment of his own homosexuality during childhood. 86 percent of the homosexual men feel it till eighteen. The selfrecognition is a way full of conflicts between ignoration and acceptance; sometimes it ends in deformation of the personality or even in suicide. For well advice of homosexual children and adolescents we indicate: firstly an early sexual education in the school including information on homosexuality and secondly the academic and postgradual education of physicians, psychologists and pedagogues on natural variants of human sexuality. PMID- 1614083 TI - [Contribution to hypochondrogenesis]. AB - Hypochondrogenesis is one of non-viable skeleton dysplasiae which recently has been delimited as an entity of its own and with its classification between spondylo-epiphysary dysplasia and achondrogenesis. An accurate differential diagnosis requires specialised histo-pathological investigations of the patient's cartilage tissue. Five new observations compared to a classical case of dysplasia spondylo-epiphysaria congenita are added to the references made in literature. PMID- 1614084 TI - [Role of the school in vaccination and prevention of infection]. AB - 628 pupils from both the northern and southern parts of West Germany (Baden Wurttemberg, Bavaria, Lower Saxony, Schleswig-Holstein) were interviewed via an "infectious diseases" questionnaire: 44 questions dealt with vaccination (vaccination history, opinions of efficiency of different vaccines), 38 with problems concerning AIDS/HIV. The results indicated significant lack in the acceptance of most of the common immunisations. Improvement of AIDS/HIV information, especially on HIV-transmission and psychosocial, economical and political consequences seems to be necessary. Possibilities of future health education for pupils are discussed. PMID- 1614085 TI - [Corneal ulcer. Current analysis from specialized ambulatory care of a clinic]. AB - A review of 115 cases of ulcerative keratitis that were diagnosed and treated at the specialized ambulatory care center for infectious eye diseases at the 2. Department of Ophthalmology over a period of eight years (January 1983-April 1991) is presented. In the analysis of the etiology nearly half (47.7%) were observed following a trauma to the epithelium, 38 (= 33.0%) were associated with contact lens wear and the third largest group (10.4%) was associated with lid problems. It is apparent that over the course of the last years the spectrum of microorganisms associated with this localized inflammation has shifted: the prevalence of Staphylococci (1983-1986 = 65%) has decreased, whereas the incidence of gram-negative rods increased (1987-1990 = 49%). In 19% Pseudomonas aeruginosa could be isolated, mostly associated with soft contact lens wear. A total of 37.5% of the staphylococci isolates were found to be resistant to gentamicin, most probably as a consequence of the widespread, indiscriminate use of this antibiotic. An updated treatment schedule is presented. PMID- 1614086 TI - [Choroid melanoma. A retrospective randomized comparative study of ruthenium irradiation vs enucleation]. AB - A randomized retrospective study concerning survival of Ruthenium treatment and enucleation in melanoma patients has been performed. For 112 patients from Hamburg who underwent Ruthenium therapy individual match partners were selected in Copenhagen where during the same period of time enucleation was the standard procedure. Selection took place concerning patient's age and sex at the time of treatment, initial tumor volume and the time of treatment. The present status of the patients was not known during the selection process. During the observation time of 12 years there was a survival rate after irradiation of 77.9% and after enucleation of 78.6%. Cox' regression disclosed a coefficient of 0.049 with a standard aviation of 0.293 and a P-value of 0.867. All parameters were showing no statistical difference between Ruthenium treated and enucleated patients. The survival rate in males was 69.2%, female patients 87.2%. For male patients there was a 2,4-fold higher risk to develop metastasis compared with female patients. Patient's age at the time of treatment correlated significantly with the prognosis. There was an increase in mortality risk by factor 1.4 per decade. PMID- 1614087 TI - [Value of corticosteroids in after-care of patients after cataract extraction and lens implantation]. AB - In two double-blind controlled trials the anti-inflammatory effects of dexamethasone were examined in post-cataract extraction eyes after lens implantation in 321 patients. In the first trial, 103 patients were included. 49 eyes received eye-drops with 0.1% dexamethasone and antibiotics, the control group of 54 eyes received the same antibiotics without any steroids. The follow up was 2 months. In the case of unexpected complications, the patients dropped out. This was the case in 48% of the steroid-group and in 79% of the control group. The main reason for this statistically significant difference were inflammatory complications in the control-group, which are difficult to quantify. The incidence of fibrinous reactions was not significantly different in the two groups, probably because of small numbers. In the second trial, we looked for fibrinous reactions. The follow-up was 3 weeks, 218 patients participated. They were divided into three groups: 71 patients received eyedrops with 0.1% dexamethasone 4x daily, 77 patients received the same drops 4x daily up to the fifth postoperative day, from then on 1x daily. 70 patients received the same drops 1x daily. A mild fibrinous reaction was seen in 10% of the high-dose-group, in 6% of the medium-dose-group and in 21% of the low-dose-group. Only the difference between the last two groups is statistically significant. We conclude that the therapy with corticosteroids after cataract extraction and lens implantation may be reduced early in the postoperative course. PMID- 1614089 TI - [Heterotopic fundus. An easily missed abnormality]. AB - This study demonstrates 12 patients with "tilted disc syndrome" which includes an inferior conus and inversion of the optic disc, sectorial ectasia of the fundus, and refractive scotoma. Knowledge of the anomaly can help to prevent the patient from repeated neurologic and neuroradiologic examinations to exclude a cerebral tumor. PMID- 1614088 TI - [Epiretinal membrane formation after pars plana vitrectomy in proliferative diabetic retinopathy]. AB - Recurrent epiretinal membranes are a major contributing factor to functional and visual failures after pars plana vitrectomy for proliferative vitreoretinal disorders. In this study 222 consecutive eyes that have had pars plana vitrectomy for proliferative diabetic retinopathy (operated in 1986 und 1987) were evaluated retrospectively. The study focuses on a subgroup of 108 consecutive eyes all with preoperative tractional retinal detachment and all operated with primary silicone oil injection. A minimum follow up of six months was present in 90% of these cases. Permanent visual success was observed in 40% of the eyes, most of which had dense vitreous hemorrhage preoperatively. Multivariant analysis revealed that among several potential risk factors recurrent epiretinal membranes as well as silicone oil were significantly associated with visual failure. Because of the high incidence of recurrent epiretinal membranes associated with poor functional results silicone oil injection following pars plana vitrectomy should be employed restrictively in patients with proliferative diabetic retinopathy. PMID- 1614090 TI - [Effect of histological criteria (TpNM classification, degree of differentiation) on mortality of patients with retinoblastoma]. AB - 153 patients suffering from retinoblastoma and treated between 1960 and 1980 were analysed retrospectively. Median follow-up was 11.2 years. 13 patients (8.5%) died from retinoblastoma. 3 patients died from a secondary osteosarcoma. The survival rates from patients with differentiated retinoblastomas did not differ from those with undifferentiated tumor cells. Optic nerve invasion decreased significantly the survival rate and involvement of the sectional line led to a survival rate after 5 years of only 22.2%. Due to 3 cases of death from secondary osteosarcoma, the survival rate of 91.14% after 5 years deteriorated to 87.64% after 10 to 14 years. PMID- 1614091 TI - [Importance of standardized photos for planimetry]. AB - In a series of 30 patients we compared the optic disc measurements. Disc photographs were either taken centric or excentric. Pictures with excentric discs showed significantly smaller measurements. However, the C/D-ratio demonstrated a good correlation (r = 0.95). For follow-up studies even not standardized photos can be useful, especially if the same examinator makes all the measurements. PMID- 1614093 TI - [Orbital teratoma--microsurgical therapy possibilities]. AB - Microsurgical removal of a large congenital orbital teratoma is reported with successful preservation of visual function. The importance of interdisciplinary work-up including neuroradiology, ophthalmology, maxillo-facial surgery and histopathology is demonstrated. During the postoperative period closed follow-up to control refraction and to treat amblyopia is mandatory to gain optimal results. PMID- 1614092 TI - [Esthesioneuroblastoma with orbital invasion]. AB - The authors report on an 83-years-old woman with esthesioneuroblastoma (ENB). The first clinical manifestation was an invasion of the suborbital and orbital region. ENB are local destructive tumours which seldom metastasize. Complete surgical excision, supplemented by irradiation therapy offers the highest cure rate. Relapses should be treated with individualized afterloading radiotherapy. PMID- 1614094 TI - [Metastatic eyelid tumors--description of clinical aspects and histology based on three cases]. AB - Clinical findings and histology of secondary lid tumors are described by example of three cases. The rare lid metastases appear mainly in three different patterns. Except cytology, which depends on the primary tumor, their morphology is quite uniform. Lid metastases of a cutaneous melanoma, a contralateral uveal melanoma and, probably reported for the second time, a leiomyosarcoma are presented. PMID- 1614095 TI - [The Excimer laser. I. The Lucerne evaluation procedure for Excimer therapy]. AB - The Excimer laser has been available for clinical applications in the Lucerne Eye Hospital since September 1990. Excimer laser keratectomy as a refractive therapy option is meeting with widespread interest among patients. As this is an invasive method whose complications cannot be neglected and for which long-term experience is so far lacking, this interest has to be balanced by extremely strict and responsible diagnosis by those offering the therapy. The authors present their evaluation concept here. The figures below document the reticence exercised in diagnosis: 1100 information leaflets dispatched are contrasted in the final analysis with only 34 laser treatments in a period of 10 months. 50 of the 200 patients admitted (referred by specialists) for preliminary examinations were definitively excluded from treatment in Lucerne as early as the administrative stage, and 61 during the clinical evaluation proper. PMID- 1614096 TI - [The Excimer laser. II. Initial experiences with the Excimer laser in Lucerne]. AB - In the period between September 1990 and July 1991, 35 patients (46 eyes) were treated with the Excimer Laser. In 25 patients (34 eyes), a Myopia-Laser-Shaping was performed, one patient was treated for both myopia and astigmatism. In eight patients (10 eyes) correction of astigmatism was carried out. Two patients with recurrent erosions and one patient with superficial scarring of the cornea were treated. The authors review their initial experience with the Excimer Laser. The decision to initiate treatment must not be undertaken lightly, because the possibility of serious complications may not be neglected. This method shows promise in selected patients with light to medium degrees of myopia. In cases of severe myopia, our experience is encouraging. Subjectively, the patients are satisfied with the results, which do not fall short of their expectations. Further research and clinical experience in this area is urgently required. PMID- 1614097 TI - [Autoregulation in the choroid]. AB - The cerebral perfusion is continuously and highly sensitively dependent on arterial pCO2. Does the ocular perfusion behave in a similar manner? To answer this question, the authors measured the following parameters before and after the inhalation of 10% CO2: a) the increase of capillary pCO2, using a transcutaneous sensor, and b) the redness (pallor) of the retinal tissue, an expression of its hemoglobin content, was measured at two retinal locations with the Ocular Photometer (OPM). Initial results from young test-volunteers and patients with documented carotis stenoses show that the choroid is able to maintain constant its blood-volume even under changing loads. PMID- 1614098 TI - [Familial occlusion of central veins associated with type II familial hyperlipoproteinemia]. AB - We report, for the first time to the best of our knowledge, about a family in which 3 members (two of which were under 40 years of age) of two successive generations presented central retinal vein occlusions in relation to a type II hyperlipoproteinaemia. On the basis of the reported cases, it can be postulated that hyperlipoproteinaemia seems to be a serious potential risk factor for central retinal vein occlusion. The particular aspects of central vein occlusion in relation to hyperlipoproteinaemia are the elevated frequency of recurrences, the poor visual prognosis secondary to severity of veinous obstruction, and the increased incidence of these occlusions in younger patients. The discovery of a hyperlipoproteinaemia in young patients with central retinal vein occlusion should therefore incite prompt examination of other family members in order to initiate prophylactic hypolipaemic treatment. PMID- 1614099 TI - [Systemic corticosteroid therapy in non-arteritic anterior ischemic optic neuropathy]. AB - A non-arteritic anterior ischemic optic neuropathy has usually a poor prognosis. Spontaneous remissions are extremely rare. In contrast to arteritic anterior ischemic neuropathy, systemic corticosteroids are generally accepted to be ineffective. Two cases of bilateral severe non-arteritic anterior ischemic optic neuropathy are reported who underwent full remission of their visual function directly related to high-dose systemic corticosteroids. It is hypothesized that, in acute phases of non-arteritic anterior ischemic optic neuropathy a significant reduction of tissue swelling and consecutive prelaminar reperfusion can be achieved with high-dose corticosteroids. PMID- 1614100 TI - [Anti-inflammatory effect of topical diclofenac sodium (Voltarene Ophta) after argon laser trabeculoplasty: preliminary results of a prospective double-blind method]. AB - Using the laser flare-cell meter (LFMC), we have previously determined the intensity and pattern of post-ALT ocular inflammation. Inflammation peak occurs 48 hours after ALT and clinically relevant inflammation is seen in 100% of pigmentary glaucomas (PIG), 75% of pseudoexfoliative glaucomas (PEXG) but only in 25% of primary open angle glaucomas (POAG). We also showed that topical diclofenac reduced inflammation in all 17 treated patients. Prostaglandins are thought to play a major role in ALT-inflammation and it is therefore logical to assume that NSAID are effective in that situation and will probably advantageously replace corticosteroids. In order to assess the anti-inflammatory effect of diclofenac drops (Voltaren Ophtha) we included a total of 37 PIG or PEXG (19 in the diclofenac and 18 in the placebo group) scheduled for ALT in prospective randomized placebo-controlled study. Visual acuity, tonometry, and LFCM flare measure were performed before, 3, 6 hours, 1, 2, 4, 7, 14 days after ALT. Topical diclofenac or placebo was given before and after ALT and then QID for a total of 4 days. Mean maximal flare increase was significantly less in the diclofenac group than in the placebo group (4.6 +/- 3.8 ph/msec v. 17.4 +/- 19 ph/msec; p less than 0.01). Flare increase compared to pre-ALT values was significant at 1 and 2 days after ALT in the placebo group only (p less than 0.02; p less than 0.05); no significant flare increase occurred in the diclofenac group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614101 TI - [Diclofenac-dexamethasone combination in treatment of postoperative inflammation: prospective double-blind study]. AB - In a prospective randomized double masked study including 40 patients we evaluated the anti-inflammatory effect of a combination of dexamethasone acetate 0.1% + diclofenac 0.1% drops compared to dexamethasone acetate 0.1% + placebo drops, after ECCE + posterior chamber lens implantation. Anterior chamber (AC) flare and cells were measured with the laser flare-cell meter Kowa FC-1000. The group receiving the dexamethasone-diclofenac combination showed a more rapid decrease of AC flare which was significant at days D3 (P less than 0.003) and D12 (p less than 0.028). The reduction of AC cells was comparable in both groups, showing however a strong tendency toward a lower cell count in the group receiving diclofenac at days D12 and D30 (p less than 0.08). Tolerance of diclofenac was good and comparable to the placebo. PMID- 1614102 TI - [Differential treatment of postoperative and uveitis-induced inflammatory cystoid macular edema]. AB - Twenty-five eyes (23 patients) with inflammatory cystoid macular edema (CME) (11 after cataract surgery and 14 eyes (12 patients) with uveitis) were followed in a prospective open study. The aim was to determine the efficiency of a combined treatment of Diamox (acetazolamide), Voltaren Ophtha (diclofenac, a NSAID) and Ultracortenol (prednisolone acetate) and in the case of treatment failure, the usefulness of posterior subtenon's injections of corticosteroids (Kenacort 40 mg (triamcinolone)). Seven eyes (all pseudophakic CMEs) responded successfully to the initial therapy. Their mean visual acuity improved from 0.31 +/- 0.13 to 0.93 +/- 0.08 after 18 +/- 5 days (p less than or equal to 0.001). Of the sixteen of 18 evaluable eyes that were additionally treated with a mean of 3.28 +/- 1.07 three-weekly posterior subtenon's injections, 15 eyes including all uveitis CME responded to treatment. Their mean visual acuity improved from 0.49 +/- 0.20 to 0.96 +/- 0.31 (p less than or equal to 0.001). Two patients were excluded; in 22/23 eyes the sequential treatment was successful with an overall success rate of 95% of cases (improvement of five lines on the Snellen chart or final visual acuity of 0.8 or better). Initial angiographic cystoid macular edema was comparable and significantly improved after therapy in the two treatment groups. No mean intraocular pressure rise was noted after steroid injections. Measurement of anterior chamber inflammation with the laser flare-cell meter (Kowa FC-1000) showed elevated flare in all cases which significantly decreased in both treatment groups and represented a good follow-up parameter for the effect of antiinflammatory treatment and restoration of blood-ocular barrier.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614103 TI - [Perimetry findings before and after surgical removal of epimacular membranes]. AB - The visual acuity and the central visual field (Octopus program M1) were analyzed before and after peeling of epimacular membranes (EMM) in 18 eyes. The EMM were classified according to their etiology as idiopathic, secondary nonvascular and secondary vascular. A large variability of initial visual field indices was found pre- and postoperatively (table 1). The least functional improvement was found following peeling of EMM with a history of more than 12 months as well as of idiopathic EMM with an initial mean defect (MD) of greater than 3 dB (fig. 8 und 9). The best success rate was achieved for eyes with idiopathic EMM and MD less than or equal to 3 dB and for eyes with secondary nonvascular EMM (fig. 6 and 7). The visual acuity but not the MD improved postoperatively in the 3 eyes with vascular EMM which had developed after a retinal vascular branch occlusion. PMID- 1614104 TI - [Chronic uveitis: course after vitrectomy]. AB - Vitrectomy is an acknowledged method in the therapy of chronic uveitis and its complications. We analysed the functional results after vitrectomy of 106 patients (121 eyes). In more than 61% of the patients, the visual acuity improved more than one line. There is less glare, and stereoscopic vision is better. In 10% of the patients, the follow-up was complicated by a retinal detachment; in contrast, a primary retinal detachment was the indication for the vitrectomy in 19%. Our study shows that vitrectomy helps reducing the frequency of recurrence of uveitis and the intensity of drug therapy. PMID- 1614105 TI - [Uveitis complicating posterior segment neovascularization. Six cases]. AB - Subretinal or preretinal neovascularisation may be occasionally observed during the evolution of certain forms of uveitis. Subretinal neovascularisation commonly begins at the level of the chorioretinal uveitic scars. Consequently, the alteration of the retinal pigment epithelium-Bruch's membrane-choriocapillaris complex is the apparent cause. Laser photocoagulation of the neovascular front, when indicated, is the treatment of choice. In contrast, preretinal neovascularisation is observed at the active stage of uveitis. Fluorescein angiography findings suggest that it is probably correlated with the importance of inflammation since in most of the cases there is no retinal ischemia. Therefore, in order to obtain a regression of the neovascular tufts the treatment should be directed against the inflammatory process. In this study the authors report five cases of subretinal neovascularisation which developed at the level of chorioretinal post-inflammatory scars and one case of papillary neovascularisation which occurred during the active stage of an unilateral intermediate uveitis and in which new vessels regressed completely following systemic steroid treatment. PMID- 1614106 TI - [Treatment of recurrent corneal erosion by puncture of Bowman's membrane]. AB - 16 patients (18 eyes) with a recurrent corneal erosion have been treated with anterior stromal punctures. The pain disappeared in 15 patients and remained unchanged for one patient. No recurrence was observed over a 18 months follow-up period (maximum 39 months) and no patient was complaining of glare. The technique is simple, effective, cheap and easily performed without special instrumentation. PMID- 1614107 TI - [The fate of corneal transplants from the Zurich eye bank]. AB - In a retrospective study, we investigated the survival of transplanted corneal material, which had been sent between 1988 and 1989 from the Zurich Eye Bank to both domestic and foreign physicians and clinics. A questionnaire was used to determine diagnosis, transplant survival, cause of any opacification, the occurrence of problems of epithelialisation, loosening of sutures, as well as vascularization of the host cornea. Of a total of 416 corneas, 327 or 79% could be evaluated. The mean follow-up periods of the various diagnostic groups ranged from 11 to 20 months, with a range of 1 to 35 months. After 18 months, the rate of clear transplants was 96% in the keratokonus group. This rate was significantly better than that of the bullous keratopathy group (77%, p less than 0.013) or that of all other diagnosis groups (72%, p less than 0.001). The difference to the 81% survival rate of the group with Fuchs' endothelial dystrophy was not significant. The most frequent cause of transplant opacification was primary transplant failure. Analysis of possible risk factors further confirmed that transplant opacification occurs more frequent in the presence of vascularization of the host cornea. PMID- 1614108 TI - [Prerequisites for the use of preserved donor tissue in perforating and lamellar keratoplasty]. AB - The longterm tissue culture is performed at the University Eye-Hospital of Hamburg since 1985 with a standardized procedure. The number of donor material and operations in the first 7 months of 1991 are reported. Preparation, storing and HLA-typing of the tissue are considered. The technical working up of the stored tissue for penetrating and lamellar keratoplasties will be explained. PMID- 1614109 TI - [Short and long-term advantages and disadvantages of prolene monofilament sutures in penetrating keratoplasty]. AB - The authors have studied the short and long-term advantages and inconveniences of Prolene monofilament sutures employed in perforating keratoplastic surgery. Contrary to Nylon, Prolene has the advantage of no structural or tensional modifications, postoperative measurements of corneal astigmatism thus remaining more stable with the time. Accordingly, where very little or no astigmatism is noted, the slight or no change in corneal refraction with time is an obvious advantage ot the patient. However, the use of Prolene in the beginning can cause some problems with continuous suture tension, either excessive or insufficient, which can result in serious complications. With training, these difficulties can be overcome and excellent results obtained. PMID- 1614110 TI - [Long-term results of congenital glaucoma microsurgery--retrospective study]. AB - Medium and long term results of trabeculotomy and goniotomy operations for primary congenital glaucomas treated in Lausanne between 1965 and 1990 were studied retrospectively. Parameters evaluated were intraocular pressure (IOP) and final visual acuity (VA). Data on IOP were available for 38 eyes. 66% underwent trabeculotomy and/or goniotomy (first group) the others needed further surgical or medical treatment (second group). IOP was equal or inferior to 19 mmHg in 88% of the first group and 62% of the second group at the end of the study (mean follow-up 13.1 years). Data on VA were available for 32 eyes. In the first group, 65% showed a VA of more than 0.5 compared to 33% for the second group. Therefore, we can consider trabeculotomy and goniotomy as early operations as advisable in first intention treatment of primary congenital glaucoma. PMID- 1614111 TI - [Comparison of the effects of trabeculoplasty using the Nd-YAG laser and the argon laser]. AB - We compared the effect of Argon Laser trabeculoplasty (ALT) and Nd-YAG-Laser trabeculoplasty (YLT) on inflammation and intraocular pressure (IOP). Twenty-two patients scheduled for bilateral trabeculoplasty were treated with an Argon laser in one eye and with Nd-YAG laser in the controlateral eye. Visual acuity, IOP and anterior chamber inflammation (measured with the laser flare-cell meter) were controlled at 0, 3, 6, 18 hours, 2, 4, 7, 14, 30, 90 and 180 days after trabeculoplasty. Our results showed a similar pressure lowering effect in both groups (-24.5 +/- 23% after YLT versus -32.9 +/- 16.3% after ALT at 90 days post laser; p = 0.26). The anterior chamber inflammation was delayed and more important in the ALT-group (inflammation peaked at 24.8 hours after YLT versus 44.5 hours after ALT; p = 0.034) (maximal mean flare increase: 19.4 +/- 12 pH/msec. after ALT, versus 16.1 +/- 11.4 ph/msec. after YLT). All eyes with inflammation were successfully treated with topical diclofenac QID (Voltaren Ophtha), a nonsteroidal anti-inflammatory agent. YLT is a safe and effective alternative technique to perform laser trabeculoplasty, which is especially useful in poorly pigmented angles where ALT is known to be less effective. PMID- 1614112 TI - [Effect of naftidrofuryl (Praxilene) in primary open angle glaucoma: prospective double-blind study]. AB - The positive effect of Naftidrofuryl (Praxilene), a specific serotonine-S2 receptor antagonist, has already been described in the treatment of normal pressure glaucoma. Despite the fact that in POAG intraocular pressure (IOP) is the primary ethiopathogenic mechanism, vascular factors could also influence the progression of the disease, especially in old patients with cardiovascular risk factors. We have studied the effect of Naftidrofuryl versus placebo in a randomised double-blind study on 42 POAG patients. Visual acuity, IOP, Visual field (Octopus program G1), Arterial pressure, Plasma viscosity have been recorded at 0, 12 and 24 weeks. Our results showed no difference between the Naftidrofuryl and the Placebo group for each studied parameter except a decrease of CLV at 12 weeks in the Naftidrofuryl group (p = 0.012). This suggests that Naftidrofuryl is not as effective in POAG as it is in normal tension glaucoma. Other studies with a greater patient - collective and the use of other vasoactive substances will be necessary in the future. PMID- 1614113 TI - [Comparison of five methods for subjective assessment of ocular cyclodeviation]. AB - METHODS: 1. simple Maddox rod (Franceschetti) 2. set of scaled large diameter Maddox rods 3. synoptophore 4. synoptometer (Cuppers) 5. dark red glass in front of the Harms tangent scale (Kolling). Whereas the first two methods allow to measure in primary position only, the other three also permit secondary and tertiary position measurements. Thirty normal subjects underwent comparative measurements by means of the above techniques in monocular and binocular condition. The median values indicate that all these methods are reliable but that certain specific differences influence the results. For this reason, pre- and postoperative measurements of ocular torsion should always be performed by the same method. The most appropriate techniques have shown to be: the set of scaled Maddox rods for measurements in primary position only, the dark red glass in front of the Harms tangent screen for measuring also in secondary and tertiary positions. PMID- 1614114 TI - [Length-tension measurement of oblique eye muscles in strabismus operations for differentiating trochlear paralysis and strabismus sursoadductorius]. AB - In a group of patients with a motility typical of a superior oblique palsy (a hypertropia increasing in adduction, in down-gaze and on head-tilt, a V-pattern and an excyclotropia), we recorded length-tension diagrams of oblique eye muscles during strabismus surgery. In 14 cases a length-tension recording was made during surgery in general anaesthesia, before and after intravenous administration of succinylcholine, that produces a fierce contraction of eye muscles. Among 14 patients that had eye motilities compatible with a superior oblique muscle palsy, 7 indeed had a non-contracting superior oblique muscle, but others had oblique muscles that contracted vividly. We also made length-tension diagrams of oblique eye muscles during strabismus surgery with local, tetracain eye-drop anaesthesia. Here, the recording was made three times, while the patient looked ahead, into the field of action of the muscle and out of the field of action of the muscle. Some patients indeed had a non-contracting superior oblique muscle and a stiff inferior oblique muscle, but others had superior oblique muscles that contracted vividly, despite an eye motility typical of a superior oblique palsy, with a positive Bielschowsky head-tilt test. This finding confirms the assumption of Kaufmann, Kolling and others that these cases have a non-paretic motility disorder. Viirre et al. found in normal monkeys that disruption of fusion by one week of occlusion of one eye allowed abberrations of conjugate horizontal and vertical eye movement like upshoot-in-adduction to become manifest.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614115 TI - [Strabismus induced by peripheral vestibular lesions]. AB - Little attention has been paid in the ophthalmological literature to strabismus resulting from lesions located in the peripheral vestibular system. However, this phenomenon is commonly encountered in clinical practice. As a rule, this kind of strabismus shows a prominent vertical component. It is generally combined with a change in perception of verticality, conjugate cyclotorsion of the eyes, and head tilt. This association is known as "ocular tilt reaction". It occurs in a number of clinical settings which are believed to be related with alteration in the otolithical and/or vertical semicircular canal pathways. Strabismus occurring as a feature of ocular tilt reaction might result from different mechanisms according to the location of the lesion, e.g. in the utricles, in the midbrain tegmentum, and in the dorso-lateral medulla oblongata. This phenomenon is illustrated here with the report of a patient suffering from Meniere disease, who underwent selective vestibular neurectomy. Methods of ophthalmological evaluation in such cases is described. PMID- 1614116 TI - [Review of 114 cases of malignant tumors of the eyelids treated surgically]. AB - The results of the surgical treatment of 114 malignant eyelid tumors, performed by one surgeon, are reported. The localization, histology and evolution of the tumors, and the significance of surgery in treatment of these lesions, are discussed. PMID- 1614117 TI - [Orbitoplasty in patients with artificial eyes]. AB - The typical signs of the postenucleation socket syndrome consist of enopthalmos, shallow lower fornix, lower lid laxity and entropion, and ptosis. It causes discomfort and can render the bearing of a prosthesis uncomfortable or impossible. The signs must be corrected in single or combined procedures. The lower fornix and the lids can be corrected with good success, enophthalmos is difficult to correct, however. PMID- 1614118 TI - [Uveal melanomas in patients less than 20 years of age]. AB - During the past 15 years we observed 21 uveal tumors in patients aged 20 years and younger. Four of them were younger than 10 years, 4 were 11 to 15 years' old, 4 ranged from 16-17 years and 9 from 18-20 years. An accelerated beam irradiation was applied in 11 cases, a surgical excision was carried out in 4 cases, and a 60 CO-applicator used for 3 patients. Three enucleations were carried out straight away. In this study we present the clinical characteristics of melanomas of young people, the therapy used, as well as the systematic analysis of the vital prognosis of the patients and of the functional prognosis of the eyes under treatment. PMID- 1614119 TI - [Retinoma and phtisis bulbi: benign expression of retinoblastoma]. AB - Systematic investigation of families of children suffering from retinoblastoma reveals more and more cases of retinoma or phthisis bulbi, cases which used to be called "spontaneous regression". Between 1975 and 1991, we have in this way discovered 11 cases (7%) certain to be carrying retinoma or phthisis bulbi, and a further 5 cases where the same diagnosis is highly probable. Of the 11 certain cases, 5 are unilateral, 6 bilateral, and 8 present family history of the disease. Of the total number of 17 eyes, 16 present retinoma, 1 phthisis bulbi. On clinical examination, all (100%) showed characteristic lesions in the form of greyish homogenous elevated masses in the vitreous cavity. 11 presented calcifications (69%) and in 14 disturbance of the pigment epithelium occurred (87%). The average follow-up is 4 years. Of the 11 patients, 8 are of procreating age and have up to now 25 offsprings. Amongst these, 15 have retinoblastoma (60%), 2 retinoma and phthisis bulbi (8%). All except one of the retinoblastoma cases are bilateral. This study would appear to show that retinoma occurs with a higher frequency than that which is usually given. The figures show clearly that retinoblastoma and retinoma derive from the same genetic disturbances, possibly at different times during cell maturation, and consequently require the same investigation and follow-up. PMID- 1614120 TI - [Discrete media clouding and its effect of contrast transfer coefficients, the pattern ERG and contrast sensitivity]. AB - As a model for our study we selected 11 pseudophacic patients with secondary cataracts who experienced good postoperative visual acuity after extracapsular cataract extraction. Besides best visual acuity and contrast sensitivity Pattern ERG (PERG) and Contrast-Transfer-Ratio (CTR) were measured before and after YAG Kapsulotomy was performed. Visual acuity and contrast sensitivity increased in all patients after treatment, whereas CTR increased in eight patients. PERG was measured in five patients, in two cases its amplitudes were higher, the other measurements revealed unchanged or lower amplitudes. Our model shows that in addition to the usual psychophysic tests, with CTR and PERG there are objective methods available to measure discrete opacities of the visual system. PMID- 1614121 TI - [Phacoemulsification: technical initiation at what price?]. AB - Phacoemulsification of the cataract is perhaps technically superior which is considered "classic". This technic consists however of a number of difficulties that may be mastered during an apprentiship. Considerable complications may arise during this initiation periods; imposing this surgical method on patients is thus an ethical problem. If the risks encountered during the apprentiship of phacoemulsification appear comparable to those during the classic extracapsular technique, phacoemulsification may be recommended with less reservation. We have compared 250 initial cases of classic extracapsular extraction with 250 "initial cases" of phacoemulsification, taking into account operative and post-operative complications and final functional results. PMID- 1614122 TI - [Pars plana lensectomy in pediatric cataract]. AB - The pars plana approach to cataract extraction in the pediatric age has several advantages. We report of 9 eyes with congenital cataract and discuss the advantages of the pars plana technic. In all cases a single surgical approach was sufficient. There were no complications postoperatively which made either surgical or medical treatment necessary. Postoperatively aphakia was corrected with contact lenses. During pars plana-lensectomie the central part of the anterior and posterior capsule is removed and an anterior vitrectomie is performed. With this procedure secondary cataract formation could always be prevented. PMID- 1614123 TI - [Results of conventional detachment surgery. I. Study planning, patients and vision results]. AB - A consecutive series of patients with retinal detachment were examined. All patients were treated primarily with buckling procedure. Patients with redetachment, bilateral detachment, vitrectomy or history of strabismus or amblyopia were excluded. Of these 155 patients, 117 could be examined. 97% of patients without macula detachment are able to keep or improve their visual acuity. 85% of those patients with macula detachment showed an improvement of visual acuity. The most important prognostic factor for the visual outcome is the duration of macula detachment. In cases of more than four days duration a visual acuity of 20/40 or more could not be expected. PMID- 1614124 TI - [Results of conventional retinal detachment surgery. II. Changes in refraction]. AB - In a comparative study we examined the refractive changes in 117 patients following conventional buckling retinal detachment surgery. Of these, 54 had a segmental scleral buckle, 18, an encircling buckle, and 45, a combination of both methods. Comprising about 2D, the changes in spherical equivalent were most marked in the patients who had combined operations. A correlation exists between buckle height and extent of refractive change (p = 0.0297). PMID- 1614125 TI - [Results of conventional retinal detachment surgery. III. Orthoptic results]. AB - In a comparative study we examined orthoptic side effects in 117 patients following conventional retinal detachment surgery. Of these, 54 had had a segmental scleral buckle, 18 a simple encircling band and 45 encircling band combined with a radial buckle. Persistent diplopia was found in 6% of cases following segmental buckles, in 11% following simple encircling procedures and in 20% following combined operations with encircling bands and segmental buckles. The incidence of diplopia was more than 30% in cases with high encircling buckles. PMID- 1614126 TI - [Peeling of epiretinal macular membranes. Results and conclusions of the Geneva Clinic]. AB - Epiretinal macular membranes can cause a lowering of visual acuity and may even lead to a total loss of foveal function in the absence of surgical procedure. The only surgical treatment is vitreo-retinal surgery with peeling of the membrane. In Geneva, we studied 23 patients, all of whom were operated for epiretinal membrane even though visual acuity was greater as 0.2, 10 membranes were idiopathic et 13 secondary. Six patients from this second group had recently undergone cataract surgery. The results were good: 83% of the patients showed an improvement in post-operative visual acuity and 60% gained 2 or more lines on the Snellen scale. The main factors for prognosis were preoperative macular cystoid edema and duration before surgery. The principal post-operative complication encountered was a secondary opacification of the lens with, to a lesser extent, cystoid edema of the macula. PMID- 1614127 TI - [Pars plana vitrectomy in uveitis]. AB - A vitrectomy was performed in 30 eyes suffering from different forms of uveitis. An improvement of visual acuity was obtained in 29 cases and was explained by removal of vitreous haze and/or of the cataract, but not by the improvement of the inflammatory process. PMID- 1614128 TI - [Vitrectomy in Terson syndrome. Report of 18 cases]. AB - A vitrectomy was performed in 18 eyes (15 patients) with vitreous hemorrhages due to Terson's syndrome. The average age of the patients was 46.5 +/- 14.4 years. The mean interval between the acute event of an intracranial hemorrhage and the vitrectomy was 6.8 +/- 4.9 months. The vitreous hemorrhage was associated with epiretinal membranes in 3, PVR in 2, and retinal breaks and/or rhegmatogenous retinal detachment in 3 eyes. The vitrectomy had to be combined with membrane peeling in 2, encircling procedures or exoplants in 4, cryotherapy in 5, endolaser in 1, and air/SF6 gas filling in 3 eyes. A missing or incomplete posterior vitreous detachment in 8 eyes was associated with a higher risk of PVR and retinal detachment. Two eyes with this condition needed 3 secondary operations. The mean follow-up duration was 32 (1 to 126) months. Two patients died 4 and 11 months after the operation. The visual acuity improved significantly following vitrectomy in all 18 eyes. The final visual acuity was better than 20/40 in 73% and 20/25 to 20/20 in 56%. The initial postoperative visual acuity decreased later on due to nuclear cataract in 7 of 10 eyes of patients over 45 years of age. A complicated cataract developed in only 1 of 8 eyes of younger patients who maintained a mean visual acuity of 20/25. Vitrectomy for Terson's syndrome is recommended in bilateral cases without spontaneous clearing of the vitreous within 3 months, as well as in cases with PVR and imminent retinal detachment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614129 TI - [Unilateral eyebrow suspension in severe unilateral congenital ptosis]. AB - The result of unilateral brow suspension in severe unilateral ptosis is said to be cosmetically and functionally not satisfactory. For the reason of symmetry, the myectomy of the levator muscle on the healthy side and the bilateral brow suspension have been recommended (Beard's law). However, we have successfully operated the affected side only in several patients without this far-reaching supplement. PMID- 1614130 TI - ["Blow-out" orbital trauma and diplopia. Conservative or surgical approach?]. AB - The treatment of orbital fractures, type blow-out, has always been discussed about. One hundred-twenty patients, subdivided in four groups were examined. Incarceration of the peri-muscular structures or not. Surgical or conservative treatment. These four groups have been studied with the purpose of establishing a treatment plan, which implicated the different time of healing up to a complete and functional recovery. Our purpose is to explain why we suggest a conservative attitude and the necessity of proceeding with radiological screening along with an examination of the binocular eyesight. PMID- 1614131 TI - [Modification of the visual field during temporary interruption of miotic treatment]. AB - The visual field of 27 eyes with chronic open angle glaucoma was examined with the "Octopus 1-2-3" automatic perimeter. The visual fields with and without miotics were compared using the "mean defect" (MD) as parameter. The MD decreases significatively (p = 0.003) after interruption of the miotic treatment. As presumed, the IOP and the pupillary diameter increased significantly (p less than 0.001). The CLV insignificatively decreased. The short term modifications of the pupillary diameter seem to be a more important factor than this of IOP. PMID- 1614132 TI - [Unexpected changes in the vitreous body after posterior detachment]. AB - After changing the position of the eye, intravitreal structures demonstrate a gravitary position at rest. As an exception the detached vitreous shows an irreversible position at rest. The vitreous tractions on retinal adhesions are therefore irregular. This could explain the asymmetric distribution of retinal tears and has to be considered for the operation techniques. PMID- 1614133 TI - [Regeneration of the optic nerve of Xenopus laevis after argon laser injury]. AB - Following mechanical lesion of the optic nerve (ON), lower vertebrates are capable of regeneration of the ON and regain visual function. We have studied, by light and electron microscopy, regeneration of the larval ON of Xenopus laevis after treatment with the argon laser. The laser energy is absorbed by the neurothelial pigment and provokes a burned crater and vesiculation in the interior of the ON. In contrast to the mechanically induced process, axons regenerate, after laser treatment, within the nerve and do not sprout into the neighboring tissue. The regenerating ON is not vascularized. Immediately after laser treatment, a loss of myelin, hypertrophy, phagocytic activity, and local rearrangement of glial cells are observed. After four weeks, myelination is still irregular. Glial cells have regained their normal aspect. PMID- 1614134 TI - [Sources of error in planimetry of the optic nerve]. AB - No matter how "sophisticated" they may seem to have become, contemporary methods for bioplanimetry of the optic disc vary in precision; easily overlooked or neglected optical influences must, indeed, be taken into consideration; and, of greatest detriment to the meaningfulness of any and all such results is the fact that even "experts" have difficulty in uniformly and reproducibly indicating where the boundaries of the optic disc and its excavation actually lie. PMID- 1614135 TI - [Degeneration of retinal cells of the rat in pressure-induced ischemia reperfusion damage: an electron microscopy study]. AB - An ischaemia-reperfusion insult to the retina was produced in one eye of 29 rats by transitory elevation of the intraocular pressure. The ultrastructural morphology of the degenerating retinal cells was studied at several time points after the insult. Three morphologically distinct types of cell death could be individualized. Type I exhibited progressive karyolysis and cytolysis and was consistent with necrosis. Type II was characterized by progressive shrinkage and condensation of the nucleus and cytoplasm followed by heterophagic elimination, thus resembling apoptosis. The main features of type III cell death were homogenization of the nucleoplasm and cytoplasm and dilatation of the perinuclear cisternae; thus, they were evocative of "non-lysosomal vesiculate" cell death. Transitional stages were observed as well. PMID- 1614136 TI - [Profile of pO2. I. Profile of transretinal pO2 in hypoxia]. AB - Transretinal PO2 measurements during systemic hypoxia, made during variations of the PO2 by steps of 10 mmHg between 120 and 30 mmHg, have shown that the PO2 values measured at the inner-retina up to half the thickness of the retina remained stable. On the other hand, those measured at the choroid and at the outer-retina decreased in a linear manner according to the variations of PaO2. These results suggest a regulation in the retinal blood flow, allowing the PO2 to remain stable for the different steps of hypoxia studied. On the other hand, the values measured at the choroid and at the outer-retina showed the absence of regulation in the choroidal blood flow during hypoxia. Systemic hypoxia may affect the metabolism of the photoreceptors and the pigmentary epithelium. PMID- 1614137 TI - [Profile of pO2. Regulation of papillary pO2]. AB - PO2 measurements using a double barelled recess type microelectrodes were measured in the optic nerve head of miniature pigs during systemic hyperoxia (100% oxygen breathing) and variations of the systemic blood pressure by intravenous injection of Adrenaline or trinitrine. During either systemic hyperoxia, or progressive variations of blood pressure, the intervascular PO2 remained stable. These results suggest a regulation of the tissue PO2 of the optic nerve head, as the retina does, at constant values. PMID- 1614138 TI - [Metabolic factors of vasomotor regulation of the inner retina]. AB - Lactic acid, the end metabolic product of anaerobic glycolysis is probably the mediator of the hypoxia induced vasodilation on retinal arterioles. In this study we explored the mechanisms of the retinal vasomotor effect of this metabolite by performing preretinal juxtaarteriolar pulsatile pressure microinjections on the intact eye of anesthetized and artificially ventilated miniature pigs. Microinjections of the levorotatory isomer L-lactic acid (pH: 2) induced a local maximal dilation of retinal arterioles. This vasodilator effect, like that of systemic hypoxia, was not mediated by the release of prostaglandins. Preretinal pulsatile pressure juxtaarteriolar microinjections of neutral-pH solution of L lactic acid also induced a segmental retinal arteriolar dilation. In contrast, microinjections of the dextrorotatory isomer D-lactic acid (pH: 2, solution), which is not produced by the retina, did not affect significantly the arteriolar diameter. Consequently, the vasodilator effect of lactic acid does not depend on periarteriolar pH modification and probably interferes with retinal metabolism since only the natural levorotatory metabolite is recognized. PMID- 1614139 TI - [Hemostatic effect of the Nd:YAG laser in cw function]. AB - The Nd:YAG laser may be effectively employed to induce blood flow stasis and vessel closure in rabbits. The mechanism by which these effects are achieved depends upon the nature of the primary absorbing structures in the irradiated tissue, as well as upon the energy level of radiation. Vascular wall damage occasioned in consequence of energy absorption in melanin granules triggers blood flow stasis according to the classic clotting cascade, defects in the endothelial cell wall being closed by aggregated platelets. In tissue lacking melanin pigmentation, energy is absorbed primarily by the haemoglobin of erythrocytes, and blood flow is arrested by coagulation of plasma proteins, platelets being absent from the impact centre. The portent of these different haemostatic mechanisms upon repair of the endothelial cell wall and neovascularization have yet to be determined. PMID- 1614140 TI - [Anterior high frequency capsulotomy. I. Experimental study]. AB - Basing on the bipolar-coaxial wetfield-diathermy, introduced in microsurgery 1974 by the author, an anterior capsulotomy instrument using a modulated RF-current was published in 1984. In the meantime several patients have been operated successfully with this technique. However, further experimental studies allowed a refining of the instrument, an improvement of the electronic control device and a perfection of the surgical technique. Today, this technique has four considerable advantages compared with other methods: the size of the capsulotomy opening is not casual but determined by the surgeon, the presence of a viscous substance in the anterior chamber definitely facilitates the optical control of the surgical procedure, the border of the capsulotomy is astonishingly resistant to mechanical forces, therefore the risk of radial capsular tears is highly reduced, the border of the capsulotomy is well defined by a tiny grayish coagulation line which facilitates the implantation. The experimental results are demonstrated. The clinical and surgical results are presented in the same journal by Coester et al. PMID- 1614141 TI - [Anterior high frequency capsulotomy. II. Clinico-surgical experiences]. AB - Using an instrument developed by Kloti, the author performed anterior capsulotomy by means of a radio-frequency current in 21 cases of extracapsular cataract extraction. This group is compared with 21 control cases. The advantages and limits of this technique are discussed. The procedure was found to be simple and very helpful to the surgeon. There was no evidence of any damage to structures in the patient's eye. PMID- 1614142 TI - [Anatomic, histologic, and morphometric studies of the ocular rectus muscles and their relation to the eye globe and Tenon's capsule]. AB - After having been the subject of several studies during the first half of the 20th century, the anatomical and morphological measurements of the ocular rectus muscles have recently been reinvestigated (e.g. L. Apt). At the Anatomy Institute in Geneva, similar measurements were performed on 25 human orbits as well as the depth of the subtenon space. The results show a large variation from one individual to another, although the "Tillaux spiral" was always respected. We have also shown that the ratio of the arc between each pair of opposed rectus muscles is a constant equal to 1 (0.997 +/- SD = 0.031). The subtenon space was defined morphometrically and confirmed histologically. All these measurements are important for practical aspects involved in the surgery of strabismus. PMID- 1614143 TI - [Regulation of papillary pO2]. AB - PO2 measurements using a double barelled recess type microelectrodes were measured in the optic nerve head of miniature pigs during systemic hyperoxia (100% oxygen breathing) and variations of the systemic blood pressure by intravenous injection of Adrenaline or trinitrine. During either systemic hyperoxia, or progressive variations of blood pressure, the intervascular PO2 remained stable. These results suggest a regulation of the tissue PO2 of the optic nerve head, as the retina does, at constant values. PMID- 1614144 TI - [Acute anterior uveitis: para-infectious hypothesis in predisposed individuals]. AB - The etiology and the physiopathology of acute anterior uveitis (AAU) is not well understood yet. However, two major predisposing factors have been identified: a bacterial infection especially with gram negative organisms (functioning as a trigger) and a genetic background, in particular the expression of HLA B-27 tissue antigen. We report the case of a young woman returning from travel to the Far East with her partner. Both presented simultaneously a gastrointestinal infection with fever and diarrhea. Despite extensive investigations, the infectious agent was never identified because of early empirical antibiotic therapy. A few days later, the patient developed AAU of a moderate grade in both eyes. HLA B-27 testing was positive for her, but not for her partner. Experimental research, based on a animal model such as endotoxin-induced uveitis (EIU), gives us some insight into the possible pathogenic mechanisms of AAU. Footpad injection of endotoxin (lipopolysaccharide component of the wall of gram negative), produce an acute anterior uveitis in rats. Extensive histologic analysis of other organs shows that the anterior segment of the eye is the only structure involved. Intensity of inflammation varies in different rat strains, stressing the importance of the genetic background. The similarity of the animal model to AAU will contribute to orient clinical research towards identifying more thoroughly the possible infectious agent at the origin of AAU and possibly to develop a prophylactic therapy. PMID- 1614145 TI - [Ocular toxocara canis in a 30-year-old adult]. AB - Pars plana vitrectomy was performed in a 30-year-old patient who presented a posterior traction detachment due to an inflammatory granuloma. The granuloma removed in toto during surgery revealed characteristic features of toxocariasis lesion (first case described in the literature). An ELISA test performed on a vitreous sample was strongly positive. Retinotomy around the granuloma was necessary to re-attach the retina and silicone oil was used as a tamponade for 4 months. VA improved from HM to 15/200 after silicone removal. PMID- 1614146 TI - [Optic neuritis in non-Hodgkin's lymphoma]. AB - Optic neuropathy during non-Hodgkin lymphoma is a late central nervous system complication of unfavourable prognosis. It appears especially with involvement of the bone marrow. A normal cerebrospinal fluid, lack of any beneficial effect of the chemo-corticotherapy and absence of papilledema suggest paraneoplastic, or iatrogenic (radio and (or) chemotherapeutic) neuropathy with conclusive histopathological proof only at autopsy. More frequently, cerebrospinal fluid containing malignant cells, papilledema and a beneficial effect of the chemocortico-therapy suggests malignant infiltration of the optic nerve as occurs in our case. Optic neuropathy during non-Hodgkin lymphoma may exceptionally precede the systemic disease by several years. Early oculomotor involvement suggests meningeal malignant infiltration as found in meningeal carcinomatosis. PMID- 1614147 TI - [Recurrent eyelid tumor in necrotizing panniculitis]. AB - To our knowledge, necrotizing lid tumors occurring in the context of a necrotizing lobular panniculitis have not yet been described in the literature. Our patient, a 75-year-old male, presented with indolent, nonmoveable subcutaneous lumps that were centrally ulcerating. They appeared first on his upper lid, then on his lower lid and thereafter on the neck, back, upper extremity and abdomen, especially in the area of his cholecystectomy scar. A thorough work-up, which included repeated histopathological examinations performed by several laboratories, led to the diagnosis of an idiopathic necrotizing lobular panniculitis. A serum level determination performed later revealed no alpha 1-antitrypsin deficiency. As the eye-lid's subcutaneous tissue lacks fat, the association between the necrotizing lid tumors and the necrotizing panniculitis appears to be a paradox. In spite of the normal alpha 1-antitrypsin serum levels--determined when the patient's lesions had long ago healed--we think in retrospect that the differential diagnosis should have included the possibility of a decreased alpha 1-antitrypsin serum level (e.g. heterozygous MZ phenotype). An alpha 1-antitrypsin level deficiency--with resulting decreased inhibition of collagenase and elastase--could account for the necrotizing process that also occurred in the eyelid's subcutaneous tissue. In the Van Gieson stain of this patient's eyelid biopsy, fragmentation of all visible collagen and elastic fibers was noted. In our opinion, the differential diagnosis does include lid involvement with secondary panniculitis caused by partially decreased alpha 1 antitrypsin serum levels and--by exclusion--idiopathic necrotizing lobular panniculitis. Therapeutic possibilities are briefly discussed. PMID- 1614148 TI - [Orbitocranial plasmacytoma: a case report]. AB - A female patient aged 79 years suffered from a unilateral, slowly progressive and painless exophthalmus. The investigations lead to the diagnosis of a voluminous plasma cell tumor involving the fossa infratemporalis, a part of the lateral orbit, as well as the middle and anterior cerebral fossae. This rare case is described and placed in its clinico-pathological context. PMID- 1614149 TI - [Spontaneous regression of an acquired arterial macroaneurysm of the retina]. AB - We report on a case of partially occluded macroaneurysm with central circinate retinopathy which showed an impressive, nearly complete, spontaneous regression after one year. Complications of macroaneurysms and indications to therapy are discussed. PMID- 1614150 TI - [Pepper and salt fundus and family anamnesis in congenital syphilis]. AB - Recognizing congenital syphilis in pediatric patients is of utmost importance with regard to therapy. The case of a 5-year-old girl with salt and pepper fundus demonstrates the importance of a thorough family history which led towards the diagnosis of congenital syphilis. This paper stresses the importance of family history in pigmented lesions of the fundus. PMID- 1614151 TI - [Primary antibiotic treatment of corneal ulcers in contact lens patients]. AB - Two patient histories show that the therapy of contact lens corneal ulcers is complicated by bacterial resistance and mixed infection. To start an effective therapy against pseudomonas, gram-negative as well as gram-positive germs, a primary combination of tobramycin with fusidic acid seems to us as reasonable. Because of possible resistance to these antibiotics a smear should be taken from the ulcer and the contact lens case before therapy is begun and the clinical evolution must be controlled. In the choice of the antibiotics, the actual state of resistance and commercial availability was taken into account. PMID- 1614152 TI - [Tumorous eyelid changes in systemic diseases]. AB - Lid tumors appear to invite the physician to make a diagnosis at first glance. This poster displays examples of lid tumors that occur in the context of malignancies, inflammatory and metabolic diseases and phacomatoses. The most frequent primary sites in metastatic eyelid tumors are the breast, the lung and cutaneous melanoma. Because of their comparatively low incidence and variable appearance these lid tumors are, at least in the beginning, often misinterpreted. Careful differential diagnosis may help in avoiding the diagnostic pitfalls of the masquerade syndromes. Lid tumors associated with sarcoidosis, lupus erythematosus discoides, lupus vulgaris, syphilis are briefly mentioned. Xanthelasmas occur more frequently in diabetics than in the normal population. About 5% of patients with xanthelasma suffer from hyperlipidemia. Neurofibromas and cavernous hemangiomas of the lid may accompany von Recklinghausen's and Sturge-Weber's diseases. PMID- 1614153 TI - [Lyme disease in Switzerland: ocular involvement]. AB - Lyme disease is a multisystem disorder caused by the spirochete Borrelia burgdorferi, which is transmitted by a tick (Ixodes Ricinus). Lyme disease is divided into three stages (infection, dissemination and immunological reactions). Ocular manifestations are rare except for conjunctivitis and facial nerve palsy. Switzerland is an endemic zone for Lyme disease; the presence of an atypical pars planitis should prompt a search for Lyme disease. PMID- 1614154 TI - [Anterior ischemia of the optic nerve and anemic retinopathy]. AB - We report on the case of a 59-year-old man with the association of an anterior ischemic optic neuropathy on the left eye and a bilateral anemic retinopathy following an extreme and prolonged post-operative anemia, because the patient had refused blood-transfusion. After one year of follow-up, the visual acuity did improve on the left eye. This association is rare, and only few cases have been reported. PMID- 1614155 TI - [Ocular complications of AIDS. Diagnostic problems]. AB - Presentation is made of the ocular complications of AIDS which were observed in the ophthalmologic clinic of the University Hospital in Zurich from 1986 to 1991. Besides cotton-wool spots, CMV-retinitis is the most frequent and best known infectious complication. In all other infections, diagnosis is most difficult, because it could never be supported by histological examination. Presentation is made of some cases of acute retinal necrosis, toxoplasmosis, cryptococcosis, candida, and of some cases of uveitis with unknown etiology. Furthermore we present one intraocular non-Hodgkin lymphoma, some suspicions of Kaposi's sarcoma and some neurologic disturbances of central origin. PMID- 1614156 TI - [Pseudotumor cerebri, clinical parameters and therapeutic modalities]. AB - Pseudotumor cerebri is a central nervous disorder with elevated intracranial pressure that is most common among young obese women. It presents with headache, transient visual obscurations and loss of central vision. Papilledema and visual field defects are frequent. Acetazolamid can be used for treatment. If medical treatment is not successful, optic nerve sheath decompression is recommended. Three patients were treated medically and there were treated surgically. Both methods stabilized or improved visual fields and central vision. PMID- 1614157 TI - [Pathogenesis and treatment of primary closed-angle glaucoma]. AB - With an incidence of about 1/1000, primary angle-closure glaucoma is 4 to 5 times less frequent than primary open-angle glaucoma. It occurs most frequently due to pupillary block, itself both due to anatomical configuration and to either physiological or pathological changes in the anterior chamber. Pupillary block causes an increase of pressure in the posterior chamber, which leads to anterior displacement of the iris and, finally, to angle closure. The treatment of choice dictated by the pathogenesis - consists of diminishing the posterior chamber pressure by means of hyperosmotic agents such as glycerin per os or mannitol iv. After reduction of the posterior-chamber pressure has been attained, a mild miotic, i.e. one which causes neither a strong miosis nor a flattening of the anterior chamber, is administered. If it is an acute attack, the application of these principles will permit normalization of pressure within about one hour. Several therapeutic guidelines are proposed, adapted to certain classical situations as well as to some less classical. PMID- 1614158 TI - [Experiences with secondary implantation of anterior chamber lenses]. AB - Between 1984-1990 80 secondary implantations of an anterior chamber lens in aphakic eyes have been completed. The average follow-up period was 3.1 years, some of the patients checked on during the last 6 years. The most relevant complications to mention being retinal detachment (2), as well as cystoid macular edema (1). These complications appeared in patients in whom a vitrectomy had to be performed simultaneously. Other complications like corneal dystrophy, glaucoma or lens dislocations were not observed. The risk is increased when there is the need to perform a vitrectomy simultaneously. In cases without vitrectomy the risk is slight. PMID- 1614159 TI - [Long-term results of secondary implantation of anterior chamber lenses]. AB - Long-term follow-up of secondary implanted anterior chamber intraocular lenses. The long-term results after secondary implantation of an anterior chamber IOL in aphakic patients are illustrated. After a mean period of 7 years after uneventful intracapsular cataract extraction 45 eyes underwent secondary implantation of an anterior chamber IOL of Symflex-Type. The mean follow-up was 40 months. During this time we observed following complications: minimal pupillary deformation (12 cases), worsening of the best corrected visual acuity (8 cases), progredient pupillary deformation (3), retinal detachment (2), pupillary block glaucoma (2), CME (1) and formation of peripheral anterior synechia (1). We discuss the alternative possibility to correct aphkia by secondary implantation of a transscleral fixated posterior chamber IOL or by epikeratophakia. PMID- 1614160 TI - [An approach to diabetic retinopathy]. AB - Presentation of ophthalmological taking in charge program of the diabetic patients, program elaborated during a symposium in London under the supervision of the World's Health Organisation and the International Federation of Diabetes. A calendar of the necessary controls is worked out. A scheme of the proposed treatment is decided. This program has to be known and followed by the patients, the general doctors and Swiss ophthalmologists. PMID- 1614161 TI - [Prognosis of penetrating keratoplasty in secondary endothelial atrophy of diverse etiology]. AB - Endothelial atrophy following cataract extraction is an increasingly important indication for perforating keratoplasty (PK). Other significant indications for PK are the treatment of endothelial atrophy following vitreous/retinal surgery for perforating injuries or primary retinal pathology. We evaluated the first year post-operative course of fourteen patients that underwent PK: 7 patients with silicon-oil induced keratopathy (group I), and 7 patients with endothelial atrophy following anterior segment surgical procedures (group II). On follow-up, group II exhibited a significant improvement of visual acuity. In group I, despite the clarity of the graft, there was no improvement of vision because of the development of retrocorneal membranes, or pre-existing or progressive retinal changes. PMID- 1614162 TI - [Correction of astigmatism after penetrating keratoplasty]. AB - Nine patients had a surgical correction of high astigmatism following perforating keratoplasty. In seven of them the reason for the perforating keratoplasty was keratoconus, in two of them Fuchs' endothelial dystrophy. The correction was performed in the seven 31-69 yrs old keratoconus patients 4-19 years (median 10 yrs) after the transplant, in the patients with Fuchs' dystrophy 13 month and 1 year following corneal transplant. In eight cases two circular shaped relaxing incisions of 60 degrees were performed in the steeper meridian, seven times combined with sutures in the opposite meridian. Once a wedge resection was performed. The astigmatism before correcting surgery was 8-19 dpt (median 13 dpt), 3-24 month (median 11 month) 1.75-13 dpt (median 8 dpt). The reduction of astigmatism was 3-10 dpt (median 8 dpt). In 5 of 9 patients the astigmatism could be corrected by spectacles, in two more patients no spectacles were prescribed because of cataract. After this series of astigmatic correction we think that incisions without sutures are superior. This method could replace rekeratoplsty in the future. PMID- 1614163 TI - [Video documentation of disordered ocular motility disorders]. AB - Demonstration of monitoring of pathological eye movements by standardized Video Documentation. The Patient is positioned in front of a circle (diameter 80 degrees or 60 degrees) with individual fixation bulbs in the secondary and tertiary gaze directions. Tapes and immediately printable freeze-pictures make precise follow-ups and therapy control possible. PMID- 1614164 TI - [Cataract Eye Camp in India, Xerophthalmia Project. Experiences last January within the scope of the Combat Blindness Foundation at the Sitapur Ophthalmology Hospital in India]. AB - In India are approximately 4 million blind people by advanced or mature cataract. For only 10 US$ one patient can be operated in eye camps in the villages by an intracapsular cataract cryoextraction an + 12.00 dptr. aphakia glasses. Also estimated four million people are blind by xerophthalmia. The project is to examine all the babies and little children in the villages and to give them for 2 years each month vitamin-A-medication. On the other side the parents of children suffering from xerophthalmia are instructed to plant vegetables rich in vitamin A. The goal of both projects is to make a cataract and xerophthalmia free zone in Uttar Pradesh, which should spread over the entire country. Both projects are sponsored by Combat Blindness Foundation, P.O. Box 5, 332 Madison Wisconsin 53705 USA, Professor Suresh Chandra, chairman. PMID- 1614165 TI - [Fluorescence angiography in ophthalmologic practice]. PMID- 1614166 TI - [Evaluating visual function with visual display graphics on the Macintosh II computer]. AB - A collection of programs has been developed on the Macintosh II computer to generate visual tests for an ophthalmological practice. The large number of available colours makes it possible to emulate most of the available tests and also to develop new ones. The system allows testing of the following visual functions: Visual acuity, Stereopsis, Aniseikonia, Phoria, Cyclophoria, Colour Vision and Contrast sensitivity. PMID- 1614167 TI - [Development and concept of a new operatory chair]. AB - We present a novel type of operatory chair which directs an operation microscope by remote control using infrared beams: XV, zoom, focal and accessories. The advantage of this system is the absence of transmission cables, and consequently represents an important improvement in terms of flexibility. It is a vast improvement as well for maintaining sterile conditions in the operation room. The ergonomics of this chair was especially designed for microsurgery. The adjustment and stability of the forearm has been considerably improved. PMID- 1614168 TI - [The eye as an art form: the ocular prosthesis]. AB - The technique of fabricating an ocular prosthesis out of glass is a rare art originating from Thuringen (formerly DDR). This technique is still practised by a few artists. A close collaboration between the ocularist and surgeon is indispensible towards achieving an optimal adaptation. We present several rules of plastic surgery enabling the cavity to receive the prosthesis after enucleation. The realization and adaptation of such a prosthesis has been filmed and will be presented. PMID- 1614169 TI - [Treatment of dyslexia with occlusion or prisms]. AB - In the German speaking part of Switzerland in the last few years there have been two singular trends in orthoptic and surgical treatment of dyslexia. Professor Otto performs occlusion to achieve dominance in one eye. Of 300 cases treated he has operated on 147 for an exodeviation. Dr. Pestalozzi prescribes prismes based on the Polatest to reach perfect binocular vision. In 175 cases he operated on 43 dyslectic children for an esodeviation. Both treatments are critically analysed and refused. PMID- 1614170 TI - [Are prism glasses a sensible measure in treatment of dyslexia?]. AB - A short summary of the characteristics of speaking, reading and writing is given, followed by the respective anatomical, physiological and neuropsychological counterparts, which are to be described as the "Hor-Denk-Sprech-Seh-Schreib Organismus" (H-D-S-S-SCH-O). Various disorders occurring in the H-D-S-S-SCH-O as well as health problems and psychological and/or sociological factors may negatively contribute to the ability of speaking, reading and writing. In each case medical and non-medical specialists should thoroughly assess the cause of the problem in order to select the most effective treatment method. An agreement was made between Dr. Pestalozzi (Olten) and the author, to asses logopedically from 1987 until 1990 at the Speech Therapy Clinic (Abteilung Klinische Logopadie, ORL-Klinik, Universitatsspital Zurich) 20 dyslexic children, aged 7 to 13 years, designated by Dr. Pestalozzi to the wearing of prism-glasses in order to cure their dyslexias. The results of this logopedic study are described and discussed. PMID- 1614171 TI - [Orthoptic treatment of dyslexia]. AB - It is assumed that dyslexia is due to a brain-organic syndrome, either congenital or acquired in infancy, with specific gnostic deficiencies and faulty controlled binocular vision. The latter is expressed by an intermittent alternating central scotoma which is thought to be responsible for impaired visual perception during reading. The aim of the orthoptic treatment of dyslexia must therefore be to eliminate the alternating central scotoma by stabilizing the binocular vision, and thus to improve reading ability by achieving unimpaired visual perception. PMID- 1614172 TI - [Further observations of dyslexia patients with prism correction]. AB - Report on 370 dyslexics, whereof 281 can be evaluated. The heterophoric cases were all corrected by Haase's method of prismatic binocular full correction. There are mainly esophorias but only little exophorias and strabisms. 3% are orthophoric. Visual acuity improved as well as sensory adaptations. The latter were mainly fixation disparities II. 82 operated cases resulted in a residual angle of 3+/-3 prism-diopters measured by Polatest. The influence on dyslexia is very good in 11%, good in 60%. 17% showed no influence on dyslexia but got rid of asthenopic symptoms. Only 12% failed. Good results are seen already after three months up to one year and in some cases even after 2 or 3 years. As optical and surgical corrections do not heal the dyslexia, it is discussed how to explain the obtained good results. The author's opinion is that prismatic corrections may save energy as the patients have no longer to compensate their heterophoria themselves. Thus they dispose on more energy e.g. for understanding of the text they are reading. PMID- 1614173 TI - [Diagnostic imaging of the brain of blind and visually handicapped young children]. AB - In infants with delayed or absent visual maturation a neuroradiological investigation of the brain is commonly performed in addition to neurophysiological examinations. We report our preliminary experience with magnetic resonance imaging (MRI). MRI allows a detailed anatomical assessment and an evaluation of the myelination, including the optic radiation. Following severe perinatal hypoxic-ischemic injury periventricular leukomalacia in the parieto occipital region was a common finding. The findings in infants with or without ocular abnormalities were heterogeneous, including normal findings, nonspecific delays of cerebral myelination as well as several malformations (such as corpus callosum hypoplasia, Aicardi syndrome, septo-optic dysplasia, migration disorders). In the individual case the neuroradiological findings do not allow to draw conclusions to the visual function and prognosis. In children with Leber congenital retinal amaurosis we have observed a normal myelination of the optic radiation. In many cases, particularly if a syndromic diagnosis is reached, neuro imaging gives useful information for prognostic and genetic counselling. PMID- 1614174 TI - [Congenital oculomotor apraxia. Presentation--developmental problems- differential diagnosis]. AB - Congenital oculomotor apraxia (COMA) was initially defined by Cogan in 1952. In this condition voluntary horizontal saccades cannot be generated, while slow horizontal pursuit movements and vertical eye movements are intact. Affected infants usually present with delayed visual and/or psychomotor development or may even appear to be blind. In the second half of the first year "compensatory" head thrust movements become apparent. While the oculomotor abnormalities tend to improve with increasing age most affected children have delayed motor and speech development. The cognitive development is commonly impaired and many children require a special scholastic education. In our personal series of 9 children we have found variable and nonspecific neuroradiological findings, including cerebellar hypoplasia, hypoplasia of corpus callosum and grey matter heterotopias. COMA has to be differentiated from acquired forms of ocular apraxia as seen in Morbus Gaucher type 3, ataxia teleangiectasia and Morbus Leigh. PMID- 1614175 TI - [Visual milestones and child development]. AB - Frequently, the milestones of visual development are the only available parameter of visual functions in newborns and small infants. The subscale eye-hand coordination of Griffith's Developmental Test and some single items of visuo motor functions were assessed concerning their first occurrence in healthy AGA term and preterm infants. Term and preterm infants differed constantly, but not significantly, in favour of the term children. No sex differences could be documented. Neurologic optimality score showed significant correlations with development of visual milestones. The Griffiths subscore at 9 and 24 months showed good correlations with later cognitive functions. PMID- 1614176 TI - [Longitudinal physical development of healthy children 0 to 18 years of age. Body length/height, body weight and growth velocity]. AB - In addition to the Dortmunder longitudinal growth study we investigated development of height, weight and height velocity in 213 healthy boys and girls 15-18 years old. Number of children decreased in the age group of 17 and 18 years old to 143. The study was performed in a longitudinal way, the measurements were taken in an one year distance. The median height gain in boys between 15 and 18 years amounted to 9.3 cm, in girls to 2.1 cm, respectively. 18 years old boys are 180.1 cm tall, girls 167.9 cm. The median increment of body weight in boys from 15-18 years amounted to 7.3 kg, in girls 4.4 kg, respectively. Median weight in 18 years old boys amounted to 65.2 kg, in girls to 58.0 kg. International comparison with other longitudinal growth studies shows a trend of somewhat higher weight, height and height velocity of the children from our study. PMID- 1614177 TI - [Treatment of disseminated intravascular coagulation with antithrombin III concentrate in children with verified infection]. AB - Consumption coagulopathy in childhood is still a serious problem. Besides treatment of the underlying diseases therapy of consumption coagulopathy was performed with heparin and nowadays with substitution of coagulation factors, especially antithrombin III concentrate, alone or in combination with heparin. We performed administration of AT III concentrates only, without additional heparin treatment in children with proven septicaemia (preterm infants n = 21, children beyond the newborn period n = 18). Antithrombin III, platelet count, fibrinogen, PT, aPTT and TT were assayed. These coagulation parameters turned to be normal 48 hours after normalisation of the antithrombin III plasma level-AT III increased to normal values within 24 hours after the initial substitution in all children. Lethal outcome was not observed after sole administration of AT III as well as no other side effects have been seen. In summary, these data indicate that consumption coagulopathy in childhood can be managed successfully with early substitution of AT III concentrate. PMID- 1614178 TI - [Thrombotic occlusion of the abdominal aorta in the neonatal period--successful thrombolytic treatment]. AB - Aortic thrombosis during neonatal period is rare and usually related to an umbilical artery catheter. In an infant (birth weight 3110 gm) with complete thrombosis of the abdominal aorta distal to the renal arteries of unknown etiology we started a fibrinolytic therapy with streptokinase at the age of 12 days (streptokinase intravenously with an initial loading dose of 3000 U/kg, maintenance 1000 U/kg/hr for 2 days). This was followed by a heparinisation (10,000 U/m2/d, 24 hours later 200 U/kg/d). 72 hours after onset of therapy there was no blood pressure difference between upper and lower limbs. Side-effects of therapy did not occur; the success of medical treatment continued after termination of the heparinisation. PMID- 1614179 TI - [Pregnancy and labor in mucoviscidosis--results of a study in Germany]. AB - Thirty-one pregnancies in 27 women suffering from mucoviscidosis have been studied in Germany, in the period from 1980 to 1991. This analysis is the largest collection of data to date relating to pregnancy and birth with mucoviscidosis after the American-Canadian study of 1980. The German study demonstrated that only women with few weak symptoms became pregnant: typically the pregnant women's mucoviscidosis was diagnosed at an average age of 9.2 years, and 96.5% of the women had a satisfactory pregravid Shwachman-Kulczicki-Score. Only minor complications were observed in these pregnancies, in particular pulmonary exacerbations (in 18 pregnancies) and an insufficient weight gain (average of 7.2 kg). Abortions were induced in five pregnancies and no spontaneous were observed. There were of maternal deaths during pregnancy or childbirth. More than one quarter of the newborns were premature. All the children had normal sweat chloride test results. 21 women could breast-feed successfully. In fifteen cases the mother's state of health deteriorated after pregnancy however only to a minor (ten cases) or moderate degree (four cases). It is noteworthy that of the twenty six infants twenty one were male. In this study we obtained the unexpected result that unaffected heterocygous children of women with mucoviscidosis are mainly male. PMID- 1614180 TI - [Serum prolactin after cerebral and psychogenic seizures in childhood and adolescence--an additional useful method for differentiating the two forms of seizure]. AB - Prolactin levels were measured immediately after the seizure in some, and 15 to 20 minutes later in all of 67 children aged between 6 months and 17 years. Values were determined after grand mal, complex partial and petit mal seizures and psychogen seizures. A more than 2 to 3 fold prolactin increase over the baseline value occurred almost always after grand mal and regularly after complex partial seizures. No hyperprolactinaemia was observed after petit mal seizures. Also after psychogenic seizures a rise in serum prolactin failed. The neurophysiological basis underlying this phenomenon is a decrease of gaba- und dopaminergic systems associated with the seizure. The described method is useful in the differential diagnosis of epileptogenic versus psychogenic seizures. PMID- 1614181 TI - [Clinical importance of hepatitis B virus DNA detection in serum of children with chronic hepatitis B]. AB - 206 sera from 172 children with chronic hepatitis B infection were tested for HBV DNA by dot blot hybridization. 111 were positive and 95 negative for HBV DNA. 103 (78.6%) of the positive patients had HBeAg and 5 (7.7%) anti-HBe. In 60 (92.3%) of the anti-HBe positive sera no HBV DNA could be detected. Children with elevated liver enzymes had HBV DNA in 80.1%, whereas in 71.6% of the chronic HBsAg carriers with normal liver enzymes no HBV DNA was found. In 87 of the 95 dot blot negative patients polymerase chain reaction was performed. 73 (83.9%) children of this group were HBV DNA positive. All HBeAg positive patients and those with elevated aminotransferases had HBV DNA in their serum. 56 anti-HBe positive HBsAg carriers were also positive; 14 were negative for HBV DNA. Our results demonstrate that viral sequences can be found in all HBeAg positive and in most of the anti-HBe positive children. Patients with ongoing virus replication have to be considered infectious and recommendation for vaccination of close relatives of these patients must be stressed. PMID- 1614182 TI - [Pilot study of amiloride inhalation in children with cystic fibrosis]. AB - Bronchial clearance is impaired in cystic fibrosis (CF). Respiratory secretions contain less sodium and chlorid, resulting in reduced airway water content. Aerosolized amiloride, a sodium transport blocker, was shown to normalize the amount of sodium in bronchial mucus, leading to an improvement in mucociliary clearance. In a controlled, double blind crossover study on nine CF children we tried to assess the efficacy of twice daily inhaled amiloride (10(-3)M) on sputum weight, consistency of sputum and lung function (FEF1, FVC, FEF50, FEF25, PEF). Each treatment period (amiloride versus 0.9% saline) lasted for two months. We could show that inhaled amiloride was able to increase mean sputum weight per day from 11.75 g (+/- 5.96) up to 18.5 g (+/- 10.34). This was equal to an increase of 57%. Some children felt that sputum expectoration lasted longer while using amiloride and that even for some hours after inhalation they expectorated a sputum-like fluid. We were able to detect, at least in some patients, that their sputum consisted of two parts, one showing more solid contents, the other more fluid-like contents. This was, however, not a consistent feature. No significant or clinical important differences were found for pulmonary function test data. There were no pulmonary or extra pulmonary side effects from treatment with amiloride. Further studies should be undertaken to assess the efficacy of longer lasting amiloride inhalation on the course of the disease in CF patients. PMID- 1614183 TI - [Meningitis in 154 children of a pediatric clinic in Germany: clinical and epidemiologic aspects]. AB - In a retrospective study, the histories of the non-neonates treated for primary meningitis in the Pediatric Department of Mainz University Hospital between 1986 and 1989 were analyzed with regard to etiological, diagnostic, clinical and epidemiological criteria. In the period studied there were 37 cases of infectious meningitis (11 Neisseria meningitidis (29.7%), 7 H. influenzae (18.9%), 3 S. pneumoniae (8.1%), 16 other (43.2%)), and 117 cases of acute aseptic meningitis syndrome (12 mumps virus (10.3%), 3 Borrelia burgdorferi (7.7%), 3 FSME (2.6%), 2 herpes simplex virus, 91 other (77.8%)). Sixty-six percent of the patients were male. Of the infants with infectious meningitis, 68% were under 5 years old. In contrast, 69% of the children with noninfectious meningitis were aged 5 or older. While 70% of the infectious meningitis cases occurred in fall and winter, 64% of the cases of acute aseptic meningitis syndrome occurred in spring and summer. In differential diagnosis between infectious and acute aseptic meningitis syndrome maximal sensitivity was a CRP value exceeding 0.5 mg/dl, a CSF lactate value of over 3 mmol/l and a CSF cell count of over 2000/3 cells. In none of the cases did a second or third lumbar puncture furnish information additional to that which could have been deduced from physical examination and course of temperature. A second lumbar puncture failed to produce unexpected results, or have consequences for therapy, in any of the 14 cases with noninfectious meningitis. Of 37 infants with infectious disease, one (2.7%) died from the sequelae of pneumococcal meningitis. Recovery was partial in 8 (22.2%) of the 36 surviving infants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614184 TI - [Opitz-trigonocephaly syndrome--a characteristic dysmorphia-retardation syndrome of unclear origin]. AB - Report on a patient with Opitz-Trigonocephaly-Syndrome who was diagnosed at the age of ten months. He had a trigonocephaly and multiple other stigmata including oblique orbital fissures, internal strabism, high and narrow palate with broad alveolar ridges, microstomia, large dysplastic ears, nuchal cutis laxa, broad clumsy fingers. Additionally he had a ventricular septal defect, was dystrophic and developmentally retarded. Chromosomal analysis was normal. A sister that was recently born showed no dysmorphic signs. So far, 24 cases have been reported in the literature. This is the 5th patient in Germany. PMID- 1614185 TI - [Craniometaphyseal dysplasia--characteristic roentgen findings]. AB - Craniometaphyseal dysplasia is a rare disorder of bone remodeling, which is characterized by hyperostosis or sclerosis of the skull combined with metaphyseal flaring of the long tubular bones. Diagnosis is only possible on the basis of the characteristic radiographic findings, these are shown in a case report of a 2 1/2 year old boy. There is no therapy of craniometaphyseal dysplasia. PMID- 1614186 TI - [Effect of psychotherapeutic interventions on weight reduction and personality development of a 13-year-old boy with Prader-Willi syndrome]. AB - A 12.10-year old boy (actual weight 88.8 kg, actual height 131.2 cm; 228% overweight) with Prader-Willi-syndrome achieved, after repeated ineffective therapy attempts over a period of 10 years, a weight reduction of 11.8 kg (185% overweight) during a 9-week in-patient treatment. In the following out-patient phase of therapy a further weight reduction of 20 kg (109% overweight) was achieved over a period of 16 months. Apart from the usual modes of action of therapy (reduced energy intake, physical exercise, behaviour modification), family therapeutic and special education interventions were used. These achieved an improvement of the patient's self-esteem, an increase in his competence to act and in his autonomy concerning his diet management, as well as a positive experience of his own abilities and social acceptance by other children and the stabilisation of the dysfunctional family system. It may be assumed that this therapeutic success is dependent on consequent compliance with the system model. PMID- 1614187 TI - The renin-angiotensin system and diabetic retinopathy. AB - The importance of the renin-angiotensin system in the eye has not been clearly established, nor is it known whether it is of importance in the evolution of diabetic retinopathy. Circulating renin is produced in the kidney and other tissues; its main importance is in the control of blood pressure. Elevated levels have been found in diabetic patients with microvascular complications. There is also some suggestion that the prorenin content is elevated in diabetics and that this is an indicator of the development of microvascular complications in the next few years. Angiotensin-converting enzyme (ACE) inhibitors have been found to reduce the leakage in early diabetic retinopathy, but it is possible that this was only due to a reduction of blood pressure. Angiotensin II was found to induce neovascularisation in corneal pocket experiments, and the replication of aortic endothelial cells has been reported. We were unable to find any increased replication of retinal endothelial cells treated with angiotensin II. It is possible that the main function of the renin-angiotensin system in the eye is the regulation of local blood flow. PMID- 1614188 TI - [Diabetic nephropathy in type 2 diabetes--epidemiology, early diagnosis and therapeutic strategies]. AB - Diabetic nephropathy now accounts for approximately one-third of all patients who develop end-stage renal disease. The realization that half of these individuals suffer from non-insulin-dependent (type-2) diabetes mellitus has sparked increased interest attempts to understand the epidemiology and pathophysiology. In particular, early diagnosis, prevention and intervention in type-2 diabetic patients with micro-albuminuria and incipient diabetic nephropathy is urgently needed, since an early mortality due to cardiovascular complications is well documented in these patients. This review article summarizes most of the new data concerning epidemiology, pathophysiology, early diagnosis and the very few intervention studies in diabetic nephropathy of type-2 diabetic patients. PMID- 1614189 TI - [Diabetic cardiopathy. Pathophysiologic concepts and therapeutic approaches]. AB - Epidemiological data reviewed suggest that diabetes itself increases the cardiac risk of diabetics (types I and II), independently from the development of coronary heart disease and in addition to other risk factors (hypertension, hypercholesterolemia, hypertriglyceridemia, smoking and others), presumably by a specific myocardial disease called "diabetic cardiopathy", or according to the recommendations of the WHO, "diabetic heart muscle disease." Disturbances of the left and right ventricular function as well as the autonomic function of the heart can be understood as signs of this specific cardiopathy. The pathophysiological mechanisms underlying this disease are not yet fully known; however, recent evidence is presented that diabetes leads to a facet of metabolic dysfunctions regarding glucose and energy metabolism, calcium homeostasis and the expression of specific proteins that diminish the ability of the heart to respond to increased workload and increase the vulnerability of the heart in diabetes. Since preliminary experimental data indicate that inhibitors of the angiotensin converting enzyme can protect the heart in diabetes, it is intriguing to suggest that increased release of angiotensin II plays a significant role in the change from reduced adaptability to irreversible damage of the heart in diabetes. PMID- 1614190 TI - Influence of dietary factors on the renal renin-angiotensin system. AB - Protein meals and infusion of amino acids cause an increase of glomerular filtration rate in humans and animals with normal renal function despite the circulating renin concentration remaining unchanged. The renal hemodynamic response is not altered by angiotensin converting enzyme inhibitors, but it is obliterated by cyclooxygenase inhibitors. By contrast, chronic exposure to high protein diets raises circulating renin and increases messenger RNA of renin (but not of angiotensinogen) in kidney tissue. Chronically high protein intake raises the glomerular filtration rate and reduces glomerular permselectivity; the reverse is seen with low protein intake. In patients with renal failure, acute amino acid infusion or protein meals cause a paradoxical drop in glomerular filtration rate which is not influenced by converting enzyme inhibitors. PMID- 1614191 TI - [ACE inhibitor effects on structure and function of the glomerular basement membrane]. AB - Metabolism of proteins which compose capillary basement membrane is altered in diabetic patients. In the kidney, this leads to an impaired permselectivity of glomerular basement membrane and consequently to onset of proteinuria. Proteinuria which is often increased by hemodynamic factors, initiates and promotes the development of diabetic glomerusclerosis. Aside from near-normal metabolic control, special antihypertensive treatment can reduce proteinuria and retard loss of kidney function in proteinuric diabetic patients. The beneficial effect of ACE-inhibitors on course of diabetic nephropathy is generally thought to be a consequence of decreased systemic and intraglomerular pressure. However, recent longterm studies in Type I and Type II diabetic patients with nephropathy showed that ACE-inhibition can reduce proteinuria independent from their hemodynamic effects and, thus, improves the filtration properties of glomerular basement membrane. This may be due to an influence of ACE-inhibition on metabolism of basement membrane proteins. PMID- 1614192 TI - [Angiotensin II and its effects on vascular structure]. AB - The peptide vasoconstrictor angiotensin II (Ang II), originally described as deriving exclusively from the plasma renin angiotensin system, has now been demonstrated to be produced independently of such sources. Local tissue angiotensin-generating systems are well documented. There is increasing evidence that these locally produced vasoconstrictor peptides may contribute to blood vessel homeostasis, as well as the development of vascular pathologies. Results obtained from pharmaceutical intervention in these systems in humans and animals strongly support this hypothesis. In addition to its vasoconstrictor properties, Ang II acts as a potent biological effector. In vitro both vasoconstrictor peptides appear to modulate the activity of autocrine feedback loops in vascular smooth muscle cells. The activity of these feedback loops in vivo may represent a central mechanism for regulation and phenotypic differentiation of this cell type. The most well-established autocrine feedback loops of vascular smooth muscle cells are constituted by platelet-derived growth factor and transforming growth factor-beta, both of which are influenced by the action of angiotensin II. The effects of the peptide vasoconstrictors on the (auto) regulated feedback loops are of long-term structural importance since both vasoconstrictors (via autocrine growth modulators) may influence the composition of the extracellular matrix of vascular smooth muscle cells. This includes effects on the synthesis and secretion of thrombospondin, fibronectin, tenascin, etc.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614193 TI - [Clinical sequelae of hyperinsulinemia in diabetes mellitus]. AB - Surprisingly enough, insulin has recently been suspected of promoting cardiovascular complications, provided it becomes effective in excess concentrations at the vascular walls. This applies to both endogenous hyperinsulinemia and insulin substitution performed exogenously with high insulin doses. Several large population studies in non-diabetics - carried out in Helsinki, Busselton and Paris - have proved recently that serum insulin concentration is an independent risk predictor for the occurrence of coronary heart disease. According to in vitro trials, insulin stimulates the proliferation of the smooth muscle cells in vascular media and the lipid synthesis, as well as lipid incorporation into the vascular wall. Very recent large-scale population studies in randomly selected type II diabetics (the Schwabing Study and one performed at Oxford) have revealed a close association between an endogenous insulin requirement, on the one hand, and the risk of macroangiopathy or coronary heart disease on the other. PMID- 1614194 TI - Statement of the AATS/STS Joint Committee on Thoracoscopy and Video Assisted Thoracic Surgery. PMID- 1614195 TI - Effect of skin temperature on platelet function in patients undergoing extracorporeal bypass. AB - Thirty-seven patients undergoing cardiopulmonary bypass operations were studied to assess the effect of skin temperature on platelet function. Differences in skin temperature between the two arms were created during bypass, at the completion of bypass, and at 2 and 24 hours after the completion of bypass. In each of 37 patients the temperature of one arm was increased with a water-filled blanket set at 40 degrees C. In 11 of these patients the other arm was allowed to equilibrate with the environment, and in the other 26 patients the arm was cooled with ice. Except for the differences in local skin temperature between the two arms, all factors known to affect the patient's bleeding time were similar. Measurements were made of bleeding times and the levels of thromboxane B2 and 6 keto-prostaglandin F1 alpha in shed blood obtained at the template bleeding time site. In the 33 patients not treated with aspirin, local hypothermia produced an increased bleeding time and a significant reduction in the thromboxane B2 level at the bleeding time site, but no reduction in 6-keto-prostaglandin F1 alpha level. Local rewarming produced a significant increase in the shed blood thromboxane B2 level. In the four patients treated with aspirin, local hypothermia produced no differences in bleeding times or shed blood levels of thromboxane B2 or 6-keto-prostaglandin F1 alpha. These data show the benefits of rewarming patients with hypothermia who have nonsurgical blood loss to restore to normal both core and peripheral temperatures before resorting to the transfusion of homologous blood products. PMID- 1614196 TI - Does desmopressin acetate prophylaxis reduce blood loss after valvular heart operations? A randomized, double-blind study. AB - The effectiveness of prophylactic desmopressin acetate in reducing hemorrhage after cardiopulmonary bypass operations is controversial. We conducted a prospective, randomized, placebo-controlled, double-blind trial to determine its effectiveness and safety in such patients. Eighty-three evaluable patients undergoing valvular heart operations were randomized to receive desmopressin (0.3 microgram/kg) (41) or placebo (42) after cardiac bypass. Demographic characteristics were similar in both groups. There was no significant difference in total 24-hour blood loss between groups (desmopressin 1064.8 +/- 647.1 ml versus placebo 844.4 +/- 507.6 ml; p greater than 0.05), or in the requirement for red blood cell, platelet, or fresh frozen plasma transfusion, or for reexploration for control of hemorrhage. Neither was there a difference in the occurrence of thrombotic complications between groups. Analysis of factor VIII activity, von Willebrand factor, or von Willebrand factor multimers failed to show significant correlations with blood loss or differences between groups except for factor VIII activity, which was significantly higher in the desmopressin group 1 hour after operation than in the placebo group. A detailed comparative analysis of similar trials to determine the reasons for different outcomes suggests that desmopressin should not be used routinely as a prophylactic agent to reduce postsurgical hemorrhage, but that it may be beneficial when used in patients who already manifest excessive bleeding postoperatively. PMID- 1614197 TI - Plasma thromboxane and pulmonary artery pressure in neonates treated with extracorporeal membrane oxygenation. AB - To examine whether neonates with persistent pulmonary hypertension are subject to a thromboxane-mediated exacerbation of their pulmonary hypertension during extracorporeal membrane oxygenator therapy (a form of partial cardiopulmonary bypass), we performed serial measurements of plasma thromboxane B2 and pulmonary artery pressure before, during, and after extracorporeal membrane oxygenation. Pulmonary artery pressure was high before extracorporeal membrane oxygenation, did not increase after the start of this therapy, but began to decrease after 48 hours of extracorporeal membrane oxygenation. During the course of extracorporeal membrane oxygenation, mean pulmonary artery pressure decreased by 50% and mean plasma thromboxane B2 levels decreased by 70%. In addition, serial plasma thromboxane B2 levels were significantly correlated with pulmonary artery pressures in individual infants with a primary diagnosis of meconium aspiration (r = 0.965 to 0.723). We speculate that the decrease in pulmonary artery pressure and plasma thromboxane B2 levels over time may reflect resolution of acute lung injury and that thromboxane B2 may play a role in regulating pulmonary artery pressure in infants with meconium aspiration. PMID- 1614198 TI - Aortic valve replacement. Aortic root versus coronary sinus perfusion with blood cardioplegic solution. AB - The role of retrograde coronary sinus cardioplegia in patients undergoing aortic valve replacement for aortic stenosis alone or in combination with myocardial revascularization has not been fully defined. Sixty-three patients undergoing elective aortic valve replacement received cold potassium blood cardioplegic solution via either the aortic root (36 patients) or the coronary sinus (27 patients). The patients were similar with respect to age, degree of aortic stenosis, ventricular function, severity of coronary artery disease, crossclamp time, completeness of revascularization, and mean volume and temperature of the infusion solution. The mean septal temperature and the release of myocardium specific isoenzyme in the first 2 hours after crossclamp removal was higher in the retrograde group (p less than 0.008). Right and left ventricular function was preserved equally in the two groups, and volume-loading studies suggested improved diastolic performance in patients having retrograde cardioplegia. There were no differences between the two groups with respect to clinical outcome. We conclude that coronary sinus cardioplegia is as safe as aortic root perfusion for myocardial preservation in patients undergoing elective aortic valve replacement. PMID- 1614199 TI - Successful long-term preservation of the neonatal heart with a modified intracellular solution. AB - Current methods of myocardial preservation for transplantation are suboptimal. A newly developed intracellular cardioplegic and storage solution (modified University of Wisconsin solution, group 1) was compared in a randomized, blinded fashion with our present clinical protocol, Stanford cardioplegic solution and saline storage (group 2) in an isolated neonatal pig model. After arrest and storage for 12 hours at 4 degrees C, biopsy specimens were taken from six group 1 hearts and five group 2 hearts for examination under an electron microscope and assessment of high-energy phosphate levels and water content. The remainder (group 1, n = 7; group 2, n = 6) were reperfused with blood for 50 minutes, after which function curves were obtained at left ventricular end-diastolic pressures of 3 to 12 mm Hg and biopsy tissue was taken. Eight control hearts (group 3) were cannulated in situ and perfused on the circuit without arrest or intervening ischemia. Stroke and minute work index curves were approximately threefold and fivefold higher for group 1 (modified University of Wisconsin solution) than for group 2 (Stanford), respectively (p less than 0.01). The hearts preserved with University of Wisconsin solution did not differ in function from unpreserved control hearts (group 3). High-energy phosphate levels were better maintained in group 1 than group 2 (p less than 0.05), and water content was lower (p less than 0.01). Semiquantitative grading of electron micrographs paralleled the functional and biochemical results. CONCLUSION: Modified University of Wisconsin intracellular solution provides markedly better heart preservation than conventionally used cardioplegic and storage solutions. PMID- 1614200 TI - New aspects of the degeneration of bioprosthetic heart valves after long-term implantation. AB - Bioprosthetic heart valves removed 76 to 150 months after implantation were morphologically investigated to correlate structural alterations with clinical failure modes. Traditional morphologic methods of evaluating valvular heterografts, such as microradiography and electron microscopy, were complemented by undecalcified ground sections, a new technique for analyzing the distribution of mineral deposits. Apart from well-investigated mechanisms that accelerate tissue degeneration, our observations point to additional facts: (1) phagocytosis of collagen fibrils and elastic material by macrophages and foreign body giant cells in areas near tears and perforations and (2) initial calcification indicated by delicate crystals in the intercellular space arranged in close relation to the periodicity of the cross-striation pattern of collagen fibrils. The present report not only calls attention to degenerative changes that are enhanced by mechanical stress but also underlines phagocytosis as an important mechanism in the destruction of bioprosthetic heart valves. PMID- 1614201 TI - Exogenous adenosine accelerates recovery of cardiac function and improves coronary flow after long-term hypothermic storage and transplantation. AB - Impaired coronary flow during postischemic reperfusion may limit functional recovery. In the present studies we used the heterotopically transplanted rat heart and the isolated working rat heart to assess whether adenosine, given during reperfusion, could improve either the rate or the extent of postischemic recovery. Hearts were arrested (2 minutes at 4 degrees C) with the St. Thomas' Hospital cardioplegic solution and stored by immersion in the same solution for 8 hours at 4 degrees C. Hearts were then transplanted into the abdomen of homozygous recipients. Immediately before reperfusion, adenosine (0.5 ml of a 1 mumol/L solution, equivalent to 0.13 micrograms) was injected into the left ventricle (control rats received an equivalent amount of saline). Hearts were reperfused in vivo for 30 minutes or 24 hours, after which they were excised and perfused (Langendorff) for 20 minutes for the assessment of function. They were then freeze clamped and taken for metabolic analysis. After 50 minutes of reperfusion, left ventricular developed pressure was 75 +/- 5 mm Hg (4 mm Hg end diastolic pressure) in the adenosine group versus 61 +/- 4 mm Hg in the control group (p less than 0.05); however, after 24 hours function was identical in the two groups (52 +/- 4 versus 52 +/- 3 mm Hg). After 50 minutes of reperfusion coronary flow was greater in the adenosine group (11.0 +/- 0.4 versus 9.7 +/- 0.4 ml/min in control rats; p less than 0.05), a difference that was sustained for 24 hours (12.8 +/- 0.3 versus 11.4 +/- 0.4 ml/min in control rats; p less than 0.05). Adenosine triphosphate and creatine phosphate contents recovered to similar extents in control and adenosine groups after both 50 minutes and 24 hours of reperfusion. In further studies with an identical storage protocol (8 hours at 4 degrees C), hearts were not transplanted but were reperfused with crystalloid medium in the Langendorff mode for 15 minutes (creatine kinase leakage measured) and in the working mode for 180 minutes. In an attempt to mimic the heterotopic transplant protocol, adenosine (1 mumol/L) was included in the perfusion fluid for the first 2 minutes of reperfusion. Similar results to those of the transplant studies were obtained, with coronary flow being consistently improved in the adenosine group; however, this benefit was lost after only 2 hours of reperfusion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1614202 TI - Effect of oxygen tension and cardiovascular operations on the myocardial antioxidant enzyme activities in patients with tetralogy of Fallot and aorta coronary bypass. AB - Since the chronically cyanotic myocardium appears to be more susceptible to reperfusion injury after cardiac operations than the noncyanotic myocardium, we studied the association between the preoperative arterial oxygen tension and the myocardial superoxide dismutase, catalase, and glutathione peroxidase activities. Fourteen patients with tetralogy of Fallot scheduled for elective operations had baseline arterial blood gas measurements done before operation. During the operation right ventricular biopsy specimens were taken for enzyme analysis immediately before cold blood cardioplegic arrest and 20 minutes after crossclamp removal. The tissue antioxidant enzyme activities of the patients with tetralogy of Fallot were compared with the myocardial results in 15 adults with stable angina pectoris having elective aorta-coronary artery bypass graft operations. Myocardial tissues removed from two patients with hypertrophic obstructive cardiomyopathy who had corrective operations were analyzed for antioxidant activities. There were no changes in myocardial antioxidant enzyme activities during the operation in the patients with tetralogy of Fallot and coronary artery bypass graft. The myocardial superoxide dismutase, catalase, and glutathione peroxidase activities correlated (0.82, 0.68, and 0.89, respectively) significantly (p values were less than 0.01, 0.05, and 0.01, respectively) with the preoperative arterial oxygen tensions in the patients with tetralogy of Fallot. The myocardial glutathione peroxidase activities were at least four times higher in the myocardium of patients with coronary artery bypass graft and hypertrophic obstructive cardiomyopathy than in that of those with tetralogy of Fallot. This study provides putative evidence that the myocardium of patients with tetralogy of Fallot is a risk of oxygen-derived free radical injury during and immediately after corrective cardiovascular operations. PMID- 1614203 TI - Age-related differences in cardiac susceptibility to ischemia/reperfusion injury. Response to deferoxamine. AB - Age-related differences in susceptibility to ischemia/reperfusion injury and the response to the iron chelator deferoxamine during reperfusion were studied in isolated nonworking rabbit hearts subjected to 30 or 40 minutes of ischemia at 37 degrees C followed by 30 minutes of reperfusion. In the experimental group, hearts received a bolus of deferoxamine just before the moment of reflow, followed by a continuous infusion during the first 10 minutes of reperfusion. Isovolumic systolic (peak developed pressure) and diastolic (diastolic pressure versus balloon volume relationship) function was assessed with an intracavity balloon and incremental volume changes. In separate groups of hearts, adenine nucleotide content (adenosine triphosphate, diphosphate, and monophosphate) was measured before ischemia, at end-ischemia, and 30 minutes after reperfusion. The cardiac function measurements showed that after 30 minutes of ischemia and 30 minutes of reperfusion, peak developed pressure in newborn hearts recovered to 89% +/- 5% of preischemic levels; this recovery was significantly better than that of adult hearts, which exhibited 67% +/- 6% (p less than 0.01) recovery. Deferoxamine significantly improved cardiac function only in adult hearts (p less than 0.01). However, after 40 minutes of ischemia and 30 minutes of reperfusion, peak developed pressure in newborn hearts was reduced to 61% +/- 3% and was not significantly better than that of adult hearts (54% +/- 5%). Deferoxamine significantly improved systolic function in both newborn and adult hearts (p less than 0.01) exposed to 40 minutes of ischemia. Myocardial adenosine triphosphate content fell markedly by the end of 30 and 40 minutes of ischemia in both groups. After 30 minutes of ischemia, newborn but not adult hearts were able to completely recover adenosine triphosphate content by 30 minutes of reperfusion. This advantage was lost after 40 minutes of ischemia. Deferoxamine had no effect on recovery of adenosine triphosphate content in any group. We conclude that (1) newborn hearts recover postischemic function and metabolism faster than adult hearts after shorter periods of ischemia; (2) this advantage is lost as the ischemic period is prolonged; (3) deferoxamine improved postischemic cardiac function after longer ischemic periods, in both age groups, but failed to improve the recovery of myocardial adenosine triphosphate content. PMID- 1614204 TI - Management of the left atrioventricular valve in the repair of complete atrioventricular septal defects. AB - Left atrioventricular valve regurgitation in atrioventricular canal defects is usually due to malalignment of the edges of the cleft or to annular dilatation. Intraoperative assessment and correction of left atrioventricular valve incompetence is critical for successful outcome in the surgical management of complete atrioventricular canal defects. Although some have elected not to suture the cleft in the setting of minimal incompetence, we have found that this often results in significant left atrioventricular valve insufficiency, necessitating reoperation. From January 1982 through December 1990, 105 patients with complete atrioventricular canal underwent definitive repair. Repair was performed with a single pericardial patch technique in 86 patients (82%). Intraoperative assessment of left atrioventricular valve competence was performed in all cases. Ninety-six patients (91%) required suturing of the cleft and 63 (60%) required annuloplasty to establish satisfactory competence of the left atrioventricular valve. The overall early mortality rate was 10.5% (11/105 patients). From 1986 to 1990, the early mortality rate decreased to 7.7% (6/78 patients). In a mean follow-up of 39 months (range 1 to 106 months), late survival was 96% (90/94 operative or early survivors). Reoperation was performed on eleven (11.5%) patients; six (6.3%) for failure of the atrioventricular valve repair, three for patch dehiscence, and two for residual ventricular septal defects. These data demonstrate that routine approximation of the cleft and aggressive use of left atrioventricular valve annuloplasty is safe and results in an excellent outcome with a low incidence of reoperation for failure of left atrioventricular valve repair. PMID- 1614205 TI - Dissolution of the Liaison Committee--rebirth of the Thoracic Surgery Directors Association. PMID- 1614206 TI - Invited letter concerning: concomitant arch repair in acute type A aortic dissection. PMID- 1614207 TI - Treatment of postoperative chylothorax by fibrin glue application under thoracoscopic view with use of local anesthesia. PMID- 1614208 TI - The dangers of gathering data. PMID- 1614209 TI - Report of neoaortic valve replacement in a ten-year-old girl after an arterial switch procedure for transposition. PMID- 1614210 TI - A fractured and detached right atrial myxoma: an unusual and threatening condition detected by intraoperative transesophageal echocardiography. PMID- 1614211 TI - The five-year evaluation of a mechanical heart valve without anticoagulation in goats. AB - Two 5-year observations of goats with microporous surfaced Bjork-Shiley Monostrut mitral heart valves without anticoagulation show the important point that one went through four the other two normal pregnancies with delivery of fourteen kids. Furthermore, the local findings on the valves suggest that the porous surface should be used only to invite a thin, endothelialized neointima over a preferably carbon-coated suture ring to continue over the groove and to the adjacent part of the valve flange. The vertical or central part of the ring and the struts, in the control material with a polished surface, have never been the origin of a thrombus and should therefore be polished. PMID- 1614212 TI - Left ventricular mechanics and energetics in the dilated canine heart: acute versus chronic mitral regurgitation. AB - The effects of volume overload associated with mitral regurgitation on left ventricular systolic mechanics, energetics, mechanical to external stroke work efficiency, and ventriculoarterial coupling were examined in 11 conscious, closed chest dogs. Miniature radiopaque tantalum markers were implanted into the myocardium to measure left ventricular volume, and biplane cinefluoroscopic images were obtained 1 week and 3 months after creation of mitral regurgitation. Echocardiographically determined left ventricular mass increased from 116 +/- 28 to 152 +/- 29 gm (p less than 0.001). Left ventricular end-diastolic and end ejection volumes increased by 24% and 27%, respectively. Global left ventricular systolic performance was assessed by the slopes (linear regression) of the end systolic pressure-volume and end-systolic stress-volume relationships corrected for change in end-diastolic volume; normalized end-systolic pressure-volume relationships fell by 36% (p less than 0.001), and normalized end-systolic stress volume relationships declined by 21% (p less than 0.005). The normalized end systolic volume at 100 mm Hg end-systolic left ventricular pressure increased from 0.63 to 0.75 (p less than 0.05). Similar results were observed based on a nonlinear (quadratic) fit of the end-systolic pressure-volume data. In terms of energetics, the slopes of the stroke volume-end-diastolic volume and pressure volume area-end-diastolic volume relationships fell significantly, indicating reduced external stroke work and mechanical energy at any given level of preload. Additionally, the efficiency of energy transfer from pressure-volume area to external pressure-volume work at matched end-diastolic volume was 25% lower (p = 0.006) at 3 months compared with the 1-week measurements. While overall effective arterial (or total vascular) elastance tended to decrease after a period of time, the effective ventriculovascular coupling ratio increased from 1.6 +/- 0.6 to 2.7 +/- 1.1 (p less than 0.005), indicating a greater degree of mismatch between the left ventricle and the total (forward and regurgitant) vascular load. Therefore the low pressure-volume overload of mitral regurgitation not only resulted in depressed left ventricular systolic mechanics but also was associated with deterioration of global left ventricular energetics and efficiency and exacerbated mismatch in coupling between the left ventricle and the systemic arterial bed and left atrium. PMID- 1614213 TI - Effects of coronary artery bypass grafting on global and regional myocardial function. An intraoperative echocardiographic assessment. AB - The immediate effect of coronary artery bypass grafting on global and regional myocardial function was studied by means of epicardial two-dimensional echocardiography during operations in 20 patients. Echocardiograms were recorded before cardiopulmonary bypass and 5 and 30 minutes after bypass. Global left ventricular function was expressed as percent short-axis area change and regional function as percent fractional area change. Segments were classified according to their baseline function as normal (percent fractional area change greater than 40%), moderately hypokinetic (percent fractional area change 21% to 40%), or severely dysfunctional (percent fractional area change less than 20%). Percent short-axis area change was significantly reduced immediately after cardiopulmonary bypass (from 42.0% +/- 4.6% to 34.9% +/- 3.0%, p less than 0.05) but had returned to baseline 30 minutes after bypass (42.6% +/- 4.0%). Similarly, function of normal and moderately hypokinetic segments decreased significantly immediately after cardiopulmonary bypass (normal segments: percent fractional area change 56% +/- 0.9% before bypass to 42.3% +/- 1.5% after bypass, p less than 0.0001; moderately hypokinetic segments: 31.0% +/- 0.9% to 25.1% +/- 1.4%, p less than 0.002). Both normal and moderately hypokinetic areas regained baseline function by 30 minutes after bypass (normal segments: 53.4% +/- 1.6%; moderately hypokinetic segments: 35.4% +/- 2.0%). In contrast, severely dysfunctional segments were found to be significantly improved immediately after bypass (14.7% +/- 0.9% before bypass to 27.7% +/- 2.1% after bypass, p less than 0.0001). This improvement was maintained 30 minutes after bypass (22.8% +/- 1.5%, p less than 0.001). We conclude that coronary revascularization exhibits an immediate beneficial effect on chronically underperfused myocardium having severely depressed baseline function. However, in normal and moderately hypokinetic areas, the depressant effects of global ischemia and reperfusion prevail in the immediate postbypass period, leading to a global depression of cardiac function. PMID- 1614214 TI - Surgery for acute dissection of ascending aorta. Should the arch be included? AB - Thirty-day and 1-, 5-, 10-, and 20-year overall survivorships among 82 patients undergoing replacement of the ascending aorta with or without the arch for acute aortic dissection between 1968 and May 1989 were 79%, 66%, 56%, 46%, and 30%, respectively. The multivariably determined risk factors for death were the inclusion of the arch in the replacement, the year of the operation, the predissection New York Heart Association functional class, diabetes, and concomitant coronary artery bypass grafting. The current 30-day survivorship predicted by the multivariable equation when the operation involves only the ascending aorta is 97%, and the 10- and 20-year predicted survivorships are 61% and 39%, respectively. When the current era the replacement involves the arch as well as the ascending aorta, the predicted 30-day survivorship is 84%, and the 10 and 20-year ones are 48% and 31%. In 1990 sixteen additional patients (one hospital death) underwent ascending aortic replacement, and six (no hospital deaths) ascending aorta and arch replacement. The predictions for 1990 from the multivariable equation were similar to these actual experiences (Ps for differences were 0.6 and 0.4). Seventy percent of surviving patients with DeBakey type I dissection were free of a second aortic operation for aneurysmal dilation of the distal false channel, but this occurred in none of nine patients in whom an intimal tear in the transverse arch was included in the resection. PMID- 1614215 TI - More than ten years' follow-up of the Hancock porcine bioprosthesis in Japan. AB - From February 1975 through October 1981, 256 Hancock porcine bioprostheses (Johnson & Johnson Cardiovascular, King of Prussia, Pa.) (60 aortic, 169 mitral, and 27 pulmonary/tricuspid position) were implanted in 220 patients (104 male and 116 female, aged 9 to 67 years; mean 43.3) at Kyushu University Hospital in Japan. The procedures include 41 aortic valve replacements, 121 mitral valve replacements, 4 pulmonary valve replacements, 6 tricuspid valve replacements, and 48 combined valve replacements (31 aortic plus mitral, 13 mitral plus tricuspid, and 4 aortic plus mitral plus tricuspid). Hospital mortality was 6.4%. Follow-up was 98% during 8 to 14 (mean 10.5) years. Cumulative follow-up was 1836 patient years and 2078 valve-years. At 10 years the overall actuarial survival rate, including hospital morality, was 70% +/- 3%, and freedom from valve-related mortality with sudden death was 87% +/- 3%. More than half of the current survivors required no anticoagulant therapy. Freedom from thromboembolism or anticoagulant-related hemorrhage (or both) and prosthetic valve endocarditis was common. Freedom from structural valve failure and reoperation declined more than 9 years after replacement of left-sided heart valves but not after replacement of right-sided heart valves. Sixty-seven patients underwent 68 repeat operations, and there were four deaths (5.9%). The rate of freedom from overall valve-related complications at 10 years was 62% +/- 8% for aortic valve replacement, 53% +/- 5% for mitral valve replacement, 80% +/- 13% for pulmonary/tricuspid valve replacement, and 42% +/- 9% for combined valve replacement. There was a significant difference between pulmonary/tricuspid valve replacement and combined valve replacement (p less than 0.05). The Hancock bioprosthesis is suitable for the replacement of valves in the right side of the heart but not for combined valve replacement. PMID- 1614216 TI - Triple sequential grafts using the internal mammary artery. An angiographic and short-term follow-up study. AB - Between December 1984 and December 1988, coronary artery bypass operations, involving the use of 119 sequential internal mammary artery grafts with three or more anastomoses per conduit, were performed in 116 patients. Patients included 14 women and 102 men, with a mean age of 60 years. They received a total of 629 anastomoses; 373 anastomoses were used in multiple sequential arterial bypass grafts; 116 sequential left and three right internal mammary artery jump grafts were performed. There were 27 patients with bilateral internal mammary artery grafts, but only 17 had completely arterial revascularizations. Perioperative infarction occurred in 3.4% of the patients; 1.7% of infarctions were related to sequential internal mammary artery grafts. There were no hospital deaths. Control angiography was performed within a month of the operation in 72 patients (with 371 anastomoses, of which 229 were in sequential arterial bypass grafts). The overall patency rate was 94.6%, and for the internal mammary artery sequential graft with three or more anastomoses it was 96.1%. The mean follow-up period was 13 months; 110 patients were in New York Heart Association class I; there was one non-cardiac-related death, and three patients (2.6%) had a late myocardial infarction. One was related to the area revascularized by the sequential internal mammary artery graft. Multiple sequential internal mammary artery bypass grafts in coronary artery disease are feasible, with a high short-term patency and a low perioperative morbidity and mortality. PMID- 1614217 TI - Platelet activating factor antagonist enhances lung preservation in a canine model of single lung allotransplantation. AB - Optimal techniques for lung preservation are yet to be defined. Platelet activating factor is a phospholipid released by a variety of cells and produces pulmonary abnormalities similar to posttransplantation pulmonary dysfunction. We investigated the strength of the effect of the platelet activating factor antagonist BN 52021 as compared with that of deferoxamine, an iron chelator previously shown to improve lung preservation. Differential lung function and pulmonary hemodynamics were used to assess preservation after a 6-hour period of cold ischemic storage in a modified canine model of left lung allotransplantation. Thirty size- and weight-matched mongrel male dogs were used for 15 transplant procedures randomized to one of three preservation techniques. The University of Wisconsin solution was used as the basic flush solution for all experimental animals. BN 52021 was added to the flush solution in one group (10 mg/kg, n = 5) and deferoxime in another group (10 mg/kg, n = 5). No additives were used for the control animals (n = 5). BN 52021 and deferoxime were administered to respective donor animals 30 minutes before organ harvesting (10 mg/kg) and to recipient animals 30 minutes before reperfusion (10 mg/kg). The pulmonary artery flush solution was administered (40 ml/kg) over 4 minutes. Recipient animals received double-lumen endotracheal tubes and were monitored with balloon-tipped, flow-directed catheters in both pulmonary arteries and dual angle ultrasonic flow probes around each pulmonary artery. Solid-state high fidelity micromanometers were used to measure pressures in the pulmonary artery, the left atrium, and the left ventricle. Systemic arterial, right and left pulmonary venous, and mixed venous blood samples were analyzed at 1, 2, 4, and 6 hours after transplantation. Pulmonary venous oxygen tension of the transplanted lung for the control group was 202 +/- 81 mm Hg versus 282 +/- 53 mm Hg for the BN 52021 group 6 hours after transplantation (p less than 0.05). Pulmonary vascular resistance of the transplanted lung for the control group was 319 +/- 54 dynes.sec.cm-5 versus 149 +/- 71 dynes.sec.cm-5 for the BN 52021 group (p less than 0.05). Proton magnetic resonance spectroscopy was performed on segments of upper and lower lobes of the native and transplanted lung from recipient animals to determine total lung water content. The BN 52021 group had a total lung water content of 57.3% as compared with 51.9% for the deferoxime group (p = not significant) and 88.6% for the control group (p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1614218 TI - Successful twenty-four-hour lung preservation with donor core cooling and leukocyte depletion in an orthotopic double lung transplantation model. AB - Donor core cooling with cardiopulmonary bypass is a valid method of clinical lung preservation. However, organ ischemia with this method is still limited to short term intervals. Since circulating leukocytes participate in postischemic injury through the release of oxygen-derived free radicals, we examined whether leukocyte depletion by mechanical filtration could extend ischemic tolerance of the lung during preservation and subsequent double lung transplantation. Bovine donor lungs were preserved by donor core cooling (10 degrees to 15 degrees C) with cardiopulmonary bypass. Donor lungs were removed, stored in 4 degrees C donor blood for 24 hours, and transplanted. Graft function was studied for 6 hours after transplantation. Group 1 animals (n = 6) underwent standard cardiopulmonary bypass with whole blood for donor and recipient procedures. In group 2 (n = 6), leukocyte filters were incorporated into the cardiopulmonary bypass circuit in both donor and recipient operations. In group 2 recipient animals leukocyte counts decreased to 3% of mean baseline values and remained low during the experiment. Postischemic lung function (assessed by systemic arterial oxygenation, pulmonary artery pressure, pulmonary vascular resistance, airway pressure, lung water content, and end-point histologic characteristics) was significantly better preserved in the animals with leukocyte depletion. Leukocyte depletion by mechanical filtration in both donor and recipient improves the ischemic tolerance of the lung beyond that provided by donor core cooling alone, resulting in excellent lung function after 24 hours of ischemia. PMID- 1614219 TI - Futility of yearly heart biopsies in patients undergoing heart transplantation. AB - Three hundred thirty-eight endomyocardial biopsies, performed as part of the routine annual evaluation at 1 or more years after transplantation in 211 patients, were reviewed. In only two instances (0.6%) were the histologic findings suggestive, but not pathognomonic, of acute rejection. Both patients were treated for rejection and are doing well at 4 and 6 years postoperatively. On the basis of the results of this study, we believe that routine yearly heart biopsies in asymptomatic patients are not necessary for long-term care of patients after heart transplantation, and we believe they should be performed only if there is clinical suspicion of rejection or as part of a research protocol. PMID- 1614220 TI - Hematologic changes during and after cardiopulmonary bypass and their relationship to the bleeding time and nonsurgical blood loss. AB - The hemostatic dysfunction induced by cardiopulmonary bypass is due, in part, to a platelet dysfunction evidenced by a postoperative extension of the bleeding time; it leads to increased postoperative blood loss and morbidity. This study, which was conducted in 85 patients undergoing cardiopulmonary bypass, was designed to characterize the hematologic changes during and after cardiopulmonary bypass and to elucidate the relationships between these changes, the extension of the bleeding time, and the magnitude of the postoperative nonsurgical blood loss. Variables were measured before, during, and 2, 24, 48, and 72 hours after cardiopulmonary bypass. Univariate and multivariate analyses were performed with either the 2-hour postbypass bleeding time or the 4-hour postbypass blood loss as the dependent variables. The reversal of the extension of the bleeding time in the postoperative period was accompanied by a significant increase in the mean platelet volume and by a significant increase in the level of thromboxane B2 measured in the blood shed from the site of the bleeding time determination. The postoperative bleeding time correlated with the postoperative blood loss, and both parameters were dependent on the duration of cardiopulmonary bypass. In addition, the postoperative bleeding time correlated with the skin temperature and the plasma level of D-dimer, while the postoperative blood loss also correlated with temperature and the plasma levels of C3. These data establish a direct relationship between the postoperative bleeding time, the postoperative blood loss, and temperature. They indicate that the reversal of the postoperative extension of the bleeding time is due in part to rewarming and to the release of larger platelets into the circulation, and they suggest that hyperfibrinolysis and complement activation may play an important role in the cardiopulmonary bypass-induced platelet dysfunction. PMID- 1614221 TI - Pulmonary function and resting breathing pattern in myotonic dystrophy. AB - In 17 patients with myotonic dystrophy, spirometric, flow-volume, and maximal mouth occlusion variables were obtained and compared with 8 normal subjects. Ventilatory CO2 response was measured by the estimation of the steady-state effect of a sufficiently large serial dead space. Variability of resting breathing pattern was expressed by the variation coefficients of respiratory cycle time and tidal volume. The group means of the total lung capacity (TLC), vital capacity (VC), forced expiratory volume in 1 sec (FEV)1 and forced inspiratory volume in 1 sec (FIV)1 showed a restrictive pattern. Only maximal static mouth pressure (Pi,max), measured at residual volume (RV) level, showed a significant positive correlation with both VC (p = 0.03) and FIV1 (p = 0.02), suggesting inspiratory muscle weakness as a determinant of the restriction. Although the differences were just not significant, both variation coefficients of the respiratory cycle time and tidal volume were larger in the group with a CO2 sensitivity below the lower limit of normal compared to those with a normal ventilatory response to CO2. In 3 patients, fluctuations in FRC were also present. We hypothesize that, in addition to the already documented FRC fluctuations by uncoordinated spontaneous intercostal muscle action, a defect of integration of afferent neural input and chemical drive in the medullary region may also be present in these patients. PMID- 1614222 TI - Neopterin in tuberculous and neoplastic pleural fluids. AB - Neopterin is derived from guanosine-triphosphate, produced by stimulated macrophages under the influence of gamma interferon of lymphocyte origin. It has been suggested as an excellent marker for activation of the monocyte/macrophage axis in some clinical situations. We evaluated its concentration in the pleural effusions of 25 individuals (10 tuberculous and 15 neoplastic) as well as in the blood of 22 of them (8 tuberculous and 14 neoplastic), comparing these levels with those of a control group in 99 normal individuals. The concentration of neopterin was determined by radioimmunologic assay. This showed a significant increase (p less than 0.001) of neopterin levels in the tuberculous pleural fluid, compared to the neoplastic group (42 +/- 23/17 +/- 9 nmol/L). In the blood, values were nearly identical to the pleural fluid (41.3 +/- 25/15.8 +/- 6.9 nmol/L), although with significant differences between them and in relation to the control group (p less than 0.001), which had a normal serum value (5.11 +/ 1.92 nmol/L). We emphasize the influence of the neopterin levels in the pleural fluid on the diagnosis of causes of pleurisy and its importance as a marker of immunologic cellular activity. PMID- 1614223 TI - Changes in the migratory ability of human lung and skin fibroblasts during in vitro aging and in vivo cellular senescence. AB - The migration of human lung and skin fibroblasts was determined during in vitro aging and in vivo cellular senescence by measuring their migration from the edge of a denuded area of a monolayer. The migration of human fetal lung fibroblasts (TIG-1 and TIG-3) decreased only very slightly with increasing passage, whereas the migration of human fetal skin fibroblasts (TIG-3S) declined gradually: the difference in cell migratory ability between early and late passages was significant (P less than 0.05). The migratory patterns of skin fibroblasts from adult and elderly donors were also similar to that of fetal skin fibroblasts. Next, the migratory abilities of fibroblast lines from adult and elderly donor groups were compared, using relatively early passaged cells. The migratory ability of the elderly-donor skin fibroblast lines was significantly lower (P less than 0.05) than that of the adult-donor skin fibroblast lines. Addition of suramin and monensin suppressed the migration of fibroblasts from fetal, adult and elderly donors, which implies that fibroblast migration is regulated by growth factors and matrix substances. The relationships between the age-dependent decline of migratory ability, growth factors and the extracellular matrix are discussed. PMID- 1614224 TI - Lifespan shortening of the nematode Caenorhabditis elegans under higher concentrations of oxygen. AB - The effects of higher concentrations of atmospheric oxygen on the lifespans of wild type and a temperature-sensitive zyg-9(b244) mutant of the nematode Caenorhabditis elegans were examined. Their mean and maximum lifespans decreased with increasing oxygen concentration. The mean and maximum lifespans of the wild type under 60, 75, and 90% oxygen shrunk by 17 and 10, 31 and 31, and 40 and 41%, respectively, as compared with those under 21% oxygen (normal air). The mean and maximum lifespan of the zyg-9(b244) mutant under 60 and 90% oxygen shrunk by 18 and 22%, and 38 and 39%, respectively, as compared with those under 21% oxygen. The Gompertz analysis of the survival data of the wild type revealed that the exponential Gompertz component, the rate of acceleration of mortality, increased with increasing oxygen concentration: i.e. the ageing was accelerated under higher concentrations of oxygen. Oxygen acts as a lifespan determinant of the nematode. When the animals were exposed to a high concentration of oxygen at the early phase of lifespan, the oxygen-induced lifespan shortening was not observed. This means that oxygen-induced damage leading to lifespan shortening is repaired under 21% oxygen and that the oxygen-induced lifespan shortening does not result from any alteration in development and/or mutation. PMID- 1614225 TI - Age-related modifications of leucine uptake in brush-border membrane vesicles from rat jejunum. AB - Leucine uptake in brush-border membrane vesicles purified from rat jejunum is sodium-dependent, sensitive to the membrane electrical potential difference and enhanced by the intravesicular presence of potassium. This last effect is not mediated by the genesis of an electrical potential difference, since potassium activation and electrical potential effects are additive. Sodium-dependent leucine Vmax (1568 +/- 91 pmol/mg per 3 s, is higher in young rats than in adult and old animals. The diffusion component of leucine transport decreases with increasing age. Preloading the vesicles with 100 mM KCl increases leucine Vmax 200% in young animals, 100% in adult and 44% in old animals. The potassium activation is a saturation function of the cation concentration. Leucine uptake in brush border membrane from old animals is less sensitive to the electrical potential difference than in membranes from adult and young animals. PMID- 1614226 TI - Differential effects of swimming and running on microsomal metabolism in middle aged and aged Fischer 344 rats. AB - Cytochrome P-450 (P-450) content as well as p-nitroanisole (pNA) O-demethylase and UDP-glucuronyltransferase (UDPGT) activities were determined in livers of middle-aged (MA; 12 or 18 months) and aged (24-26 months) rats exercised by either treadmill running or swimming. In addition, aniline hydroxylase activity was measured in MA runners and aged swimmers and compared to respective sham and non-handled controls. Treadmill exercise consisted of running aged and MA rats on a motorized treadmill for 16 and 20 m/min respectively, 60 min/day and 4 times per week, for 8 weeks. Sham rats were placed on the treadmill twice per week for 5 min at 8 m/min. No differences were found in any parameter comparing sham rats to non-handled controls. Running did not affect body weight or hepatic microsomal protein during the 8-week study. A 33-35% decline in microsomal P-450 content in treadmill exercised MA and aged rats was found. PNA O-demethylase activity was decreased 30% in MA and 45% in aged runners and aniline metabolism was inhibited 21% in MA rats. UDPGT activity was not affected by running in MA or aged rats. Swimming exercise was accomplished by placing the rats in a tank of water (32-33 degrees C) filled to a depth of 2 ft. Swim time was 60 min twice daily, 5 times per week. The aged and MA rats were trained for 6 months and 1 year, respectively. Two control groups, non-swimming sedentary (dry control) and 1 min swim/day sham (wet control), were utilized. MA and aged wet controls and swimmers weighted 8% and 15% less respectively, than MA and aged sedentary rats. Microsomal protein was significantly increased in MA swimmers compared to sedentary (20%) and wet control (35%) but no change was found with swimming in the aged rats. The results of the enzymatic studies were variable in the MA rats. Increases in P-450 content were found in wet controls (16%) and swimmers (27%) of the MA group, but only the swimming change was significant. No significant change was determined for pNA metabolism between swimmers and wet (22%) or dry (17%) controls. Aged swimmers and wet controls were more consistent, with no change in any of the parameters except aniline metabolism which was significantly increased in wet controls (25%) and swimmers (28%) as compared to dry controls. No significant change in UDPGT activity was measured in either age group of swimmers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1614227 TI - The effect of age on mitogen responsive T cell precursors in human beings is completely restored by interleukin-2. AB - It is well known that the function of T lymphocytes is significantly impaired by advancing age. In the present study, attempts have been made to further characterize the T cell impairment of elderly subjects. Thus, we have performed limiting dilution microculture analysis to evaluate the precursor frequency of T lymphocytes responding to a mitogenic stimulus in old and young subjects. Furthermore we have evaluated the activity of recombinant interleukin-2 (rIL-2) on these cells. The results demonstrate that in older subjects the frequency of these precursors is significantly decreased. The in vitro treatment with rIL-2 increased the frequency of mitogen responsive T lymphocyte precursors in both groups so that the difference between the two groups was not significant. Thus present results extend the findings demonstrating that older subjects display an impairment of T cell functions and that IL-2 treatment may correct these alterations. In particular, they confirm the hypothesis that age-associated functional changes are more likely due to diminished numbers of reactive cells, than to a decline in the activity of all cells. PMID- 1614228 TI - Appropriateness of care. A comparison of global and outcome methods to set standards. AB - The RAND-UCLA Health Services Utilization Study previously analyzed the appropriateness of use of carotid endarterectomy based on a literature review and global expert judgments. In this study, for 45 of the same clinical indications used in the RAND-UCLA Study, the authors compare the appropriateness judgments based on the global judgment method to appropriateness ratings based on probability estimates of specific outcomes that were provided by the same panel of experts. The authors asked these experts to estimate, for each clinical indication, the likelihood of important medical outcomes (i.e. stroke within a year) in the presence and absence of endarterectomy. Using decision analysis, the appropriateness of endarterectomy for these 45 indications was then calculated. For only two of the eight physicians were the Spearman rank-order correlations between these two methods of judging appropriateness significant and positive. (Correlations for the eight physicians ranged from 0.45 to -0.38). This result was produced by: 1) the tendency of the experts to estimate relatively poor outcomes for seriously ill patients whether or not endarterectomy was performed; and 2) a far less consistent effect of clinical factors on outcome estimates than on global judgments. Better methods for incorporating probability estimates into a global rating process must be developed. The authors found excellent agreement between the panelists' relative outcome estimates for common endarterectomy indications and the observed stroke rate for these same indications, suggesting that one promising method is to use specific outcome data to "anchor" expert judgments. PMID- 1614229 TI - Falling, health status, and the use of health services by older adults. A prospective study. AB - In this study, data from the Longitudinal Study on Aging were used to prospectively assess the relationship between repetitive falling or falling only once in the year before baseline and changes in health status and the use of health services. Multiple and logistic regression were used to control for a variety of known covariates, in addition to the baseline values of the target outcomes. Repetitive falling was associated with decreased health status, measured by various activities of daily living and disability indices, at both 2- and 4-year follow-ups. One fall, however, was never associated with deteriorating health status. Similarly, repetitive falling was related to a decreased likelihood of visiting a physician (at the first follow-up, only), but to an increased likelihood of hospitalization, nursing home placement, and death (at both follow-ups). Falling just one time, however, was only associated with an increased likelihood of nursing home placement. Based on outcome trajectories, two subpopulations of repetitive fallers were identified. One subpopulation was consistent with the rapid deterioration hypothesized by the "spiral" response to falling, and includes about 35% of the repetitive fallers (i.e., those who die within 4 years of baseline). The other subpopulation was consistent with the initial decline and subsequent stabilization hypothesized by the "drop stabilization" response. PMID- 1614230 TI - The dynamics of health insurance among the near elderly. AB - Data from the Longitudinal Survey of Income and Program Participation were used to examine the dynamics of health insurance among persons 55 to 64 years of age. Persons in this age range are especially vulnerable to incurring high health care costs. Between the summer of 1983 and early 1986, 21% of persons 55 to 64 years of age experienced some time without health insurance. Approximately one fifth were continuously uninsured (4%) while the rest spent only part of the time without coverage, typically 4 months or less. Women were particularly vulnerable to periods without insurance, accounting for approximately twice as many of them as did men. Unlike younger cohorts, the coverage lost among the near elderly tended not to be employer coverage. Instead, most uninsured spells were ones in which individually purchased coverage was lost. Most spell beginnings were unrelated to changes in household employment, yet most spells ended when employment within the household increased. Some currently proposed reforms to expand health insurance, such as an all-employer mandate, a "pay-or-play" mandate, and extending Medicaid to persons in poverty, are less effective in reaching this medically high-risk population than in reaching younger persons who are uninsured. PMID- 1614231 TI - Hospital and patient characteristics associated with death after surgery. A study of adverse occurrence and failure to rescue. AB - We asked if the factors that predict overall mortality following two common surgical procedures are different from those that predict adverse occurrences (complications) during the hospitalization or death after an adverse occurrence, which we refer to as "failure to rescue." We examined 5,972 Medicare patients undergoing elective cholecystectomy or transurethral prostatectomy using three outcome measures: 1) the death rate (number of deaths/number of patients); 2) the adverse occurrence rate (number of patients who developed an adverse occurrence/number of patients); and 3) the failure rate (number of deaths in patients who developed an adverse occurrence/number of patients with an adverse occurrence). The death rate was associated with both hospital and patient characteristics. The adverse occurrence rate was associated primarily with patient characteristics. In contrast, failure to rescue was associated more with hospital characteristics, and was less influenced by patient admission severity of illness as measured by the MedisGroups score. We concluded that factors associated with hospital failure to rescue are different from factors associated with adverse occurrences or death. Understanding the reasons behind variation in mortality rates across hospitals should improve our ability to use mortality statistics to help hospitals upgrade the quality of care. PMID- 1614232 TI - Physician charges in the hospital. Exploring episodes of care for controlling volume growth. AB - Medicare physician payments are growing rapidly. At least 40% of the annual growth is due to volume increases. Reforms passed in 1989 include volume performance standards that attempt to control volume by linking future physician fee increases to volume growth. There is concern that defining the entire nation as the risk pool will result in an unworkable volume performance standard. One way to improve incentives is to create a separate volume performance standard for in-hospital physician services, define bundles of services related to the hospital stay, and place the medical staff of the hospital at risk for volume growth. To forestall the unbundling of services outside the stay, windows could be defined around the stay. This study reports physician services during the stay and in windows around the stay. In so doing, the study creates the knowledge base necessary to design better volume control policies and judge among alternative window definitions. Using 1987 data, this study presents average physician charges by type of service during: 1) the hospital stay; and 2) 1-month windows before and after the stay. For all admissions, 85% of charges occur during the stay and 15% occur during the windows (windows for surgical admissions and medical admissions are 9% and 23%, respectively). Pre- and postwindows are roughly symmetrical and average charges per day gradually increase before the admission and decline after discharge. A small physician panel commented on the clinical appropriateness of the one month windows. The panel indicates that defining in-hospital episodes of physician care is feasible. PMID- 1614233 TI - The impact of clinical pharmacists' consultations on physicians' geriatric drug prescribing. A randomized controlled trial. AB - The impact of clinical pharmacists' consultations on geriatric drug prescribing was studied in a prospective randomized controlled trial of patients 65 years of age and over discharged on 3 or more medications for chronic conditions from a 450-bed community hospital. The pharmacists provided consultation to experimental patients and their physicians at hospital discharge and at periodic intervals for 3 months postdischarge. Using a standardized tool, a physician-pharmacist panel, blinded to study group assignment of patients, evaluated the appropriateness of prescribing for a random sample of 236 patients. Eighty-eight percent had at least one or more clinically significant drug problems, and 22% had at least one potentially serious and life-threatening problem. Drug-therapy problems were divided into six categories: 1) inappropriate choice of therapy; 2) dosage; 3) schedule; 4) drug-drug interactions; 5) therapeutic duplication; and 6) allergy. Experimental patients were less likely to have one or more prescribing problems in any of the categories (P = 0.05) or in the appropriateness (P = 0.02) or dosage (P = 0.05) categories. A summary score, measuring the appropriateness of the patient's total drug regimen, indicated that experimental patients' regimens were more appropriate than those of controls (P = 0.01). Results of this trial reveal that clinical pharmacists can improve the appropriateness of geriatric drug prescribing in outpatient settings. PMID- 1614234 TI - Inflammation and the allergic response. AB - The atopic diseases--allergic rhinitis, asthma, and atopic dermatitis--are chronic inflammatory diseases characterized by an exacerbating and remitting course and can only rarely be associated causally with allergen exposure. The challenge to ascribe an allergic basis to these diseases is derived from the apparent inability to reconcile these chronic inflammatory features with a process thought to be initiated by the rapid release of mediators after the interaction of allergen with IgE-coated mast cells. The traditional understanding has been that mast cell activation results in the release of a series of preformed and rapidly synthesized substances that mediate the immediate onset of vasodilatation, vascular leakage, smooth muscle contraction, and irritant nerve receptor stimulation. These mediators, however, are rapidly degraded and are not thought to be associated with a significant inflammatory component. Recent studies, however, have established that the interaction of allergen with the immune system is, in fact, far more complex (Fig. 4). In addition to mast cell activation, allergen can interact with and activate T-lymphocytes and mononuclear phagocytic cells, leading to the secretion of cytokines and other inflammatory substances. Furthermore, the interaction of allergen with the mast cell may be far more complex, with the potential to stimulate the delayed release of newly synthesized cytokines. The interaction of allergen with the immune system also promotes the secondary release of inflammatory neuropeptides. Thus, the known spectrum of mediators released after allergen exposure has vastly been expanded. These include numerous still uncharacterized chemotactic and activating peptides; eicosanoids such as 5-HETE, 12-HETE, and leukotriene B4; platelet-activating factor; several proteases; neuropeptides and, most importantly, the cytokines. These mediators recruit and activate neutrophils, monocytes, basophils, and eosinophils, attract additional lymphocytes and mononuclear phagocytic cells, and induce mast cell proliferation with further mast cell degranulation. A vicious cycle subsequently develops, with further inflammation and tissue destruction. Thus, the interaction of allergen with the immune system has become a complex cascade capable of producing the chronic inflammatory changes characteristic of allergic diseases. PMID- 1614235 TI - Urticaria and angioedema. AB - Urticaria and angioedema are usually the clinical consequence of vasoactive mediators derived from mast cells in the skin or mucosal tissues. Efforts to classify mast cell-mediated causes of urticaria and angioedema have generally been frustrated by their diverse pathogenesis and clinical course. The term acute is typically used to describe fleeting lesions whose recurrence does not extend beyond 6 weeks. Chronic is the term used to describe lesions that persist for more than a few hours but usually less than a day, and recurrences extend for more than 6 weeks. These definitions do not take histology into account. Skin biopsies of fleeting lesions demonstrate a paucity of inflammatory cells, whereas more persistent lesions display a spectrum of perivascular cuffing by predominantly T cells and monocytes. The presence of leukocytoclastic vasculitis in persistent lesions indicates an underlying immune complex disease. Many of the physical urticarias have fleeting lesions that can be induced with the appropriate stimulus for years. This review article has emphasized the clinical course and histology of urticaria and angioedema lesions in an effort to provide a more complete understanding of the pathogenesis and appropriate treatment. Clearly, avoidance of an identifiable inciting stimulus is optimum management, although most patients have no etiology defined or the cause is not realistically avoidable. At present, treatment options for these patients rely on antihistamines to control the immediate consequence of mast cell degranulation. Corticosteroids are reserved for the treatment of patients whose urticaria or angioedema lesions persist, reflecting the increasing involvement of mononuclear cells in the disease process. For leukocytoclastic vasculitis, corticosteroids are indicated, and cytotoxic drugs may be required for adequate treatment. Future treatments of urticaria and angioedema will evolve based on elucidation of the relevant cells and soluble mediators and will include counterregulatory or antagonistic peptides and drugs. C1 esterase inhibitor deficiency is a relatively uncommon cause of angioedema but is important to understand because of its ability to clinically mimic mast cell-mediated angioedemas and its unique pathogenesis and treatment. HAE can be divided into two serologic subtypes that simply reflect the location of the defect in one of the codominantly expressed C1 INH genes on chromosome 11. AAE can be divided into two serologic subtypes. AAE type I is due to massive consumption of C1-INH, presumably by tumor-related immune complexes. AAE type II is due to an anti-C1-INH autoantibody.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1614236 TI - Anaphylaxis. AB - The syndrome of anaphylaxis is a life-threatening event in which the potential for patient morbidity and mortality is high. An understanding of the pathophysiology of anaphylaxis, the most serious of the allergic disorders, is paramount for its diagnosis. In addition to these elements, this article discusses newly recognized causes of anaphylaxis and reviews its treatment. PMID- 1614237 TI - Drug allergy. AB - Although allergic drug reactions are just one type of adverse reaction to medications, they are clinically very important because of the morbidity and mortality they cause. An ever-expanding pharmacopeia increases the potential for allergic drug reactions. An understanding of the types of allergic drug reactions, their immunopathologic mechanisms, and the most likely medications involved; an approach to determine the drug responsible for the reaction; and ways to prevent future allergic drug reactions are important features in minimizing patient morbidity. PMID- 1614238 TI - Stinging insect allergy. AB - Insect sting anaphylaxis is a relatively common problem estimated to affect at least 0.4% of the population and is responsible for at least 40 deaths per year in the United States. The allergic reactions are mediated by IgE antibodies directed at constituents in honeybee, yellow jacket, hornet, and wasp venoms. In addition, increasing numbers of reactions occur from fire ant stings, non-winged Hymenoptera present in the Southeastern United States. The anaphylactic symptoms are typical of those occurring from any cause. Most reactions in children are mild, frequently involving dermal manifestations (hives, edema) only. The more severe reactions, such as shock and loss of consciousness, can occur at any age but are relatively more common in adults. Following sting anaphylaxis, approximately 50% of unselected patients will continue to have allergic reactions to subsequent stings. The natural history of the disease process is influenced by the severity of the anaphylactic symptoms. Children with dermal reactions only have a benign course and are unlikely to have recurrent reactions. Patients with more severe reactions are at risk for repeat anaphylaxis. Patients with a history of insect sting anaphylaxis and positive venom skin tests should have epinephrine available and are candidates for subsequent venom immunotherapy, which provides almost 100% protection against subsequent re-sting reactions. Recommendations for the duration of immunotherapy are evolving. Venom therapy can be stopped if skin test reactions become negative. For most patients, 3 years of therapy appears adequate, despite persistence of positive venom skin tests. PMID- 1614239 TI - Respiratory infections and asthma. AB - Airway responsiveness is increased during respiratory virus infections, both in subjects with asthma and without underlying pulmonary disease. Furthermore, the airway hyperresponsiveness is altered for a prolonged period of time, weeks or months after the viral illness has subsided. This article reviews the possible mechanisms of virus-associated airway hyperresponsiveness, including the complex interplay of IgE-dependent reactions, changes in autonomic nervous system function and inflammation, epithelial damage, effects of viruses on the cellular immune response, and enhanced late-phase response. PMID- 1614240 TI - Occupational asthma. AB - Occupational asthma is recognized as the most common form of occupational lung disease. Over 200 causative substances have been described. Major cases of occupational asthma are discussed along with valuable diagnostic approaches. Early diagnosis and removal of the patient from workplace exposure to the causative substance can prevent progression to severe asthma. PMID- 1614241 TI - Environmental control of indoor air pollution. AB - Indoor air pollution is becoming an increasing problem in industrialized countries. Most people spend their time indoors which results in chronic exposure to indoor allergens and irritants. New products have been introduced to the environment to which humans are not immunologically adapted. This article describes the main sources of indoor air pollution and the best ways to control exposure to indoor air pollutants. PMID- 1614242 TI - Allergen immunotherapy. Review of efficacy and current practice. AB - The modern use of allergen immunotherapy is described. Evidence for efficacy in inhalant allergy and insect sting allergy is reviewed. Current indications for allergen immunotherapy are discussed. PMID- 1614243 TI - Avulsion of the anomalous facial nerve at stapedectomy. AB - Injury to the facial nerve in an anomalous location overlying the oval window at the time of stapedectomy has rarely been reported. The authors recently have encountered three patients with such injuries. The facial nerve was found at the time of reexploration to run directly over the oval window. A fourth patient was explored primarily for a conductive hearing loss and the same anomalous course was discovered. The purpose of this report is to alert the otologic surgeon to this rare but potentially catastrophic anomaly and to review the pertinent embryology and management of these malformations. PMID- 1614244 TI - S-100 protein in human inner ear: use of a novel immunohistochemical technique on routinely processed, celloidin-embedded human temporal bone sections. AB - The authors recently developed a new antigen retrieval technique which allows immunohistochemical detection of proteins in routinely processed, celloidin embedded human temporal bone sections. This technique was used in the present study, which reports the occurrence of S-100 protein in the human inner ear. Fifteen celloidin-embedded human temporal bone sections, obtained from the Eastern Temporal Bone Bank at the Massachusetts Eye and Ear Infirmary, were tested with the monoclonal antibody to S-100. This protein was found in the spiral ligament, in Reissner's membrane, in the spiral limbus, and in the basement membrane of the cochlea. S-100-positive, thin fibers could be seen as supporting elements in the acoustic nerve and the facial nerve. This protein was localized along the surface of vestibular wall. The new technique provides an immunohistochemical approach to studying routinely processed human temporal bone sections and may prove useful in the field of immuno-otopathology. PMID- 1614245 TI - Tracheoesophageal complications of thyroid disease. AB - Fine needle aspiration (FNA) biopsy in thyroid diagnosis has significantly reduced the need for diagnostic thyroidectomy. The relative proportion of therapeutic thyroid surgery is therefore increasing and, since a significant number of therapeutic procedures are indicated to alleviate tracheoesophageal complications, surgeons are likely to be confronted with an increasing percentage of potentially challenging cases in the face of declining thyroidectomy caseloads. All thyroidectomies done at the authors' institution from 1987 through 1990 were studied in order to assess the potential impact of FNA on thyroid surgery and to specifically analyze the management of those cases accompanied by tracheoesophageal complications. It is concluded that 18% of the 87 thyroidectomies in this series could possibly have been avoided had FNA been obtained routinely. The clinical manifestations and surgical management of those cases associated with tracheoesophageal complications are presented. General therapeutic strategies for such cases are also summarized. PMID- 1614246 TI - Facial electroneurography: analysis of techniques and correlation with degenerating motoneurons. AB - Facial electroneurography is the one electrophysiologic test that quantifies the degree of nerve degeneration. This two-part study establishes electroneurography (ENoG) as a reliable and valid system of measurement. Part I examines three different ENoG techniques in normal subjects and in patients with advanced paralysis. Myogenic compound action potential (CAP) absolute amplitudes differ according to methodology, site, and gender. Analyses of side-to-side and test retest CAP differences demonstrate optimized and standardized recording lead techniques to be comparable and consistent when CAPs are recorded in the midface. The most significant variable is time, i.e., the inconsistency of test-retest results. The coefficient of reliability increases when averaging results of test sessions repeated at a similar point in time. Part II, an animal model, supports the correlation between ENoG predictions following facial nerve injury and the level of motoneuron degeneration, as assessed by retrograde transport of horse radish peroxidase to the somata of the facial motor nucleus and by peripheral axon counts. PMID- 1614247 TI - Intraoperative measurement of the elastic modulus of the vocal fold. Part 1. Device development. AB - Although the concept of manipulating laryngeal biomechanics to improve vocal function is not new, there has been a recent proliferation in surgical techniques used to affect laryngeal function. These include methods which increase the stiffness of the vocal folds, medialize the vocal folds, alter the pitch by changing the tension of the vocal folds, and augment the tissues using injection of alloplastic materials. Despite these new and possibly revolutionary methods, no means are presently available to surgeons to intraoperatively evaluate and optimize results of a surgical intervention. This study involved the development of a device to measure the in vivo elastic modulus of the vocal folds. PMID- 1614248 TI - Intraoperative measurement of the elastic modulus of the vocal fold. Part 2. Preliminary results. AB - This paper presents initial clinical experience using a device capable of measuring the transverse elastic modulus of the vocal fold. These initial results indicated that the device may be useful in determining stiffness inequalities between the vocal folds. PMID- 1614249 TI - Hearing preservation in acoustic neuroma surgery: a continuing study. AB - Hearing preservation in acoustic neuroma surgery is possible in a limited number of cases. Although there have been many articles published about hearing preservation, there have been few studies of long-term hearing results, nor is it known if there is an increased rate of tumor recurrence when hearing preservation is attempted. Twenty-two patients who underwent a hearing preservation procedure via the retrosigmoid approach were selected from 80 consecutive patients with cerebellopontine angle tumors operated on from February 1984 to November 1987. Useful hearing was retained in 11 cases as reported in a previously published study. Seven patients continue to have useful hearing after 3 to 5 years; 3 have shown a gradual but slight decline. There has been no tumor recurrence in these patients, but 2 patients, operated on early in the series and who had lost hearing, had recurrent tumor. PMID- 1614251 TI - Granular cell tumors of the trachea. AB - In contrast to the relative frequency of granular cell tumors (GCT) in the larynx and bronchi, the occurrence of these tumors in the trachea is rare. A 50-year review of the English-language literature disclosed only 24 described cases of tracheal GCT. This report reviews the clinicopathologic data from those 24 cases, along with the data from 2 cases obtained via a personal communication and the data from 4 previously unpublished cases obtained from a 30-year review of the Armed Forces Institute of Pathology archives. Tracheal resection was the predominant mode of therapy and often was performed as a salvage procedure for failed endoscopic excisions. Recommendations for a more uniform approach to surgical management are provided. PMID- 1614250 TI - Study of the performance of four prelinguistically or perilinguistically deaf patients with a multi-electrode, intracochlear implant. AB - Individuals who are born deaf or become deaf in early childhood and are implanted as adults (or in late adolescence) with a multi-electrode, intracochlear implant often cannot understand speech by audition alone. Test results of four implanted patients were analyzed to determine 1. if there was a difference in performance between patients; 2. if there was a relation between performance and history of auditory stimulation; and 3. which tests revealed performance differences. On audition-only and audition-plus-vision tests, overall performance was rank ordered from lowest to highest for patients 1, 2, 3, and 4, respectively. Patient 4 recognized a few words audition-only. Patients 1 and 2 had long periods of no auditory stimulation; patients 3 and 4 had long periods of auditory stimulation with hearing aids prior to implantation. Tests not revealing differences in performance were identified. PMID- 1614252 TI - Promontory electrical stimulation in postoperative acoustic tumor patients. AB - Complete deafness can follow acoustic tumor surgery and results from labyrinthine injury, auditory nerve trauma, and/or vascular compromise. A central auditory prosthesis is one potential rehabilitative strategy in such patients. Anatomical studies suggest that some spiral ganglion cells may survive after vascular occlusion, and we have demonstrated responses to electrical stimulation in patients after labyrinthectomy. It was thus hypothesized that patients deafened after a hearing conservation attempt, but maintaining an intact auditory nerve, could utilize an intracochlear implant. To investigate this possibility, promontory electrical stimulation was performed on three patients who had tumors less than 2 cm and who had serviceable preoperative hearing, but no responses postoperatively. Behavioral responses and electrically evoked auditory brainstem and middle latency responses were obtained from two patients, one of whom was 6 years postsurgery. These data indicate that a cochlear implant may be possible after acoustic tumor surgery. PMID- 1614253 TI - Comparison of vasoconstrictors for functional endoscopic sinus surgery in children. AB - Three different vasoconstricting agents were evaluated during functional endoscopic sinus surgery (FESS) in 57 children. Oxymetazoline hydrochloride 0.05%, phenylephrine hydrochloride 0.25%, or cocaine 4% was applied to the nasal mucosa in a prospective, randomized, double-blind fashion. Heart rate and blood pressure changes were recorded 5 and 10 minutes after application of the study vasoconstrictor to each nostril. The surgeon's subjective impressions of bleeding and visualization were recorded for each side of the nose, as were total blood loss and anesthesia time. Although all three vasoconstrictors were tolerated well by the children, there was a suggestion that heart rate decreased more at 5 minutes with phenylephrine than with oxymetazoline or cocaine (P = .08) and that blood pressure increased more at 10 minutes with phenylephrine than with oxymetazoline or cocaine (P = .1). No arrhythmias were noted. Subjective scoring for bleeding showed that children receiving oxymetazoline were less likely to receive scores of "more" bleeding than usual (3/38 vs. 10/34 for phenylephrine and 10/35 for cocaine, P less than .02). Subjective scoring for visualization showed that children receiving oxymetazoline were also less likely to receive scores of "worse" visualization than usual (3/38 vs. 12/38 for phenylephrine and 9/35 for cocaine, P less than .01). There was no difference in surgical bleeding or visualization between children receiving phenylephrine and children receiving cocaine. In our institution, 0.05% oxymetazoline is the preferred vasoconstrictor for FESS in children. PMID- 1614254 TI - Reduction of hypertrophic earlobes. PMID- 1614255 TI - Surgical anatomy of the vertebral artery at the skull base. PMID- 1614256 TI - V-wedge crura resection in nasal tip surgery. PMID- 1614257 TI - A new simple technique for tracheoesophageal puncture. PMID- 1614258 TI - Tissue response following CO2 laser application in apical surgery: light microscopic assessment in dogs. AB - The potential advantages of CO2 laser in apical surgery have not been established histologically. Therefore, the long-term effects of CO2 laser on the apical and periapical tissues were examined histologically in dogs 6 months after apical surgery. Lased specimens and unlased controls showed periapical inflammatory and osteogenic reactions. Lased root surfaces revealed craters with a superficial charred layer closely associated with new cementum-like matrix. The subjacent dentin appeared tubule-free and eosinophilic. Lased bone trabeculae showed a charred layer with a deeper osteocyte-free zone. The charred layer was covered by new bone. Detached charred segments in the marrow space and periapical inflammatory infiltrate were intimately associated with multinucleated giant cells, some containing minute char particles. Such cells were absent from the root and trabecular char linings. In addition, the charred surfaces were free of hard tissue resorption. These results suggest that CO2 laser does not hinder healing when applied in apical surgery. PMID- 1614259 TI - Holmium:YAG laser recanalization. PMID- 1614260 TI - "Photodynamic therapy in gastrointestinal cancer". PMID- 1614261 TI - Detection of calcified atherosclerotic plaque by laser-induced plasma emission. AB - The use of fluorescence spectroscopy to discriminate atherosclerotic from normal tissue is limited by a lower sensitivity for calcified than noncalcified atherosclerotic plaque (65% vs. 93%, respectively). To evaluate plasma emission as a means to detect calcified plaque, 325 normal and atherosclerotic cadaveric aortic sites were irradiated through a 100-micron silica fiber in blood by a pulsed holmium laser (lambda = 2.1 microns, fluence = 4 J/mm2). A photodiode positioned near the proximal end of the fiber detected plasma emission during a laser pulse. Plasma emission was detected at 0% (0/110) of normal, 0% (0/107) of noncalcified atherosclerotic tissue, and 91% (98/108) of calcified atherosclerotic sites. Spectroscopic analysis confirmed the presence of calcium lines in the plasma emission from calcified atherosclerotic plaque. Although ablative fluences (greater than 3 J/mm2) were required for plasma generation, a single laser pulse ablated only to a depth of 67 +/- 16 microns in normal tissue. In an additional 10 calcified atherosclerotic sites, laser ablation was continued as long as plasma emission was detected. In all cases, plaque ablation was terminated before arterial perforation. Furthermore, the adjunctive use of plasma detection improved the accuracy of fluorescence spectroscopic classification of normal and atherosclerotic tissue. In conclusion, plasma detection has a high sensitivity (91%) and specificity (100%) for calcified atherosclerotic plaque and may be a useful adjunct for laser angioplasty guidance. Furthermore, plasma detection can be implemented both simply and inexpensively. PMID- 1614262 TI - Monitoring myocardial reperfusion injury with NADH fluorometry. AB - Using NADH fluorometry to monitor myocardial metabolism, the mechanism of reperfusion injury was investigated after the delivery of an experimental reperfusate. Using an isolated working heart preparation, rat hearts underwent 15 min of global ischemia at 37 degrees C. Following the ischemic insult, an oxygenated enriched reperfusion solution was given for 5 min. The hearts were then returned to a working state and aortic flow recorded to evaluate recovery. NADH levels were monitored throughout the experiment with a fluorometer and glycogen, AMP, ADP, and ATP were measured biochemically pre- and postischemia, after reperfusion and after recovery. In this study, reperfusion injury was best abated by an enriched reperfusate. Our results indicate the mechanism for this amelioration is not high-energy phosphate replenishment. Rather, as indicated by NADH fluorescence, the hearts attain an intermediate level of metabolism that permits glycogen to be restored and functional recovery to be improved. PMID- 1614263 TI - Transurethral laser prostatectomy in the canine model. AB - A technique for performing transurethral prostatectomy was devised using a Neodymium:Yttrium Aluminum Garnet laser in a canine model. Six dogs underwent transurethral laser prostatectomy following establishment of a perineal urethrostomy. The efficacy of the prostatectomies was judged by retrograde urethrography, transrectal prostate ultrasonography, cystoscopy, and histologic examination. The method of applying laser energy while holding the tip of the fiberoptic light guide 2-3 mm away from the prostate was ineffective; with power ranging from 40 to 70 watts, this technique resulted mainly in coagulation necrosis and removal of only a small amount of tissue. However, placing the tip of the light guide in direct contact with the prostate and using power from 70 to 100 watts produced impressively large prostatectomy defects by tissue vaporization. We conclude that this newly devised technique for transurethral prostatectomy in the canine model can be performed safely and effectively using a Neodymium:Yttrium Aluminum Garnet laser (Neodymium:YAG). PMID- 1614264 TI - Microbeam laser-injured neurons increase in vitro astrocytic gap junctional communication as measured by fluorescence recovery after laser photobleaching. AB - An important aspect of the neuronal-astrocyte relationship is the interaction of reactive astrocytes with injured and/or dying neurons. Few studies have focused on the signaling of astrocytes by injured neurons or on the possibility that neurons can alter astrocytic gap junctional communication. The purpose of this study was to determine whether the presence of injured neurons could alter astrocytic gap junctional coupling by establishing an in vitro method of microbeam laser neuronal injury and coculturing these neurons with astrocytes. Neurons from two rat neuronal clonal cell lines were injured using a 20-W argon laser operating on the ultraviolet (UV) multiline (351-361 nm) directed through a X40 objective of an inverted microscope. After laser injury, the glass slide with the injured neurons was sandwiched with a slide on which primary rat astrocytes were grown. Although the neurons and astrocytes were bathed in the same medium, they were not in direct contact during the coculture period (24, 48, or 72 hr). Astrocytic gap junctional dye coupling was examined using the fluorescence recovery after laser photobleaching (gap-FRAP) analysis technique. Astrocytes cocultured with the injured neurons for 24 to 48 hr did not show a significant difference in fluorescence recovery when compared to control values. After 72 hr of coculture, there was a significant increase in the gap junctional dye coupling. These results indicate that injured neurons influence in vitro astrocytic gap junctional conductance after 72 hr of coculture as measured by dye coupling. PMID- 1614265 TI - Ultraviolet laser-induced fluorescence of colonic tissue: basic biology and diagnostic potential. AB - Laser-induced fluorescence (LIF) of colonic tissue was examined both in vitro and in vivo to assess the ability of the technique to distinguish neoplastic from hyperplastic and normal tissue and to relate the LIF spectra to specific constituents of the colon. Spectra from 86 normal colonic sites, 35 hyperplastic polyps, 49 adenomatous polyps, and 7 adenocarcinomas were recorded both in vivo and in vitro. With 337-nm excitation, the fluorescence spectra all had peaks at 390 and 460 nm, believed to arise from collagen and NADH, and a minimum at 425 nm, consistent with absorption attributable to hemoglobin. The spectra of colonic tissue recorded both in vivo and in vitro are different, primarily in the NADH fluorescence component, which decays exponentially with time after resection. When normal colonic tissue is compared to hyperplastic or adenomatous polyps, the predominant changes in the fluorescence spectra are a decrease in collagen fluorescence and a slight increase in hemoglobin reabsorption. A multivariate linear regression (MVLR) analysis was used to distinguish neoplastic tissue from non-neoplastic tissue with a sensitivity, specificity, predictive value positive, and predictive value negative toward neoplastic tissue of 80%, 92%, 82%, and 91%, respectively. When the MVLR technique was used to distinguish neoplastic polyps from non-neoplastic polyps, values of 86%, 77%, 86%, and 77% respectively, were obtained. The data suggest that the LIF measurements sense changes in polyp morphology, rather than changes in fluorophores specific to polyps, and it is this change in morphology that leads indirectly to discrimination of polyps. PMID- 1614266 TI - Preliminary results of intraoperative excimer laser angioplasty: phase 1: an adjunct to coronary artery bypass surgery. AB - The excimer laser underwent phase I clinical trials at three centers to determine its safety for intraoperative coronary laser angioplasty as an adjunct to coronary artery bypass grafting. A 308-nm Xenon-Chloride, pulsed-wave excimer laser was used to perform angioplasty in 30 patients undergoing coronary artery bypass surgery. Forty vessels (30 patients) were treated, in which the extent of occlusion ranged from 30% to 100%, with complete occlusion in 40% of all vessels. Improvement in vessel luminal caliber was achieved in 33 (79%) vessels, with perforations occurring in 4 (12%) vessels, 2 of which required surgical repair. The lumens of the remaining 8 (19%) vessels were not enlarged, and 2 (5%) of these vessels were perforated. Luminal enlargement was most often achieved in totalled occluded vessels in which 16/17 (94%) were recanalized. No patients died within 30 days postoperatively. Five patients demonstrated biochemical and electrocardiographic evidence of myocardial injury 48 hr postoperatively, and one patient died of cardiac arrest 139 days postoperatively. On the basis of these results, we believe that excimer laser angioplasty can be performed safely to improve coronary luminal patency, even in totally occluded vessels, in an operative setting. The long-term value of this procedure remains to be elucidated. PMID- 1614267 TI - Bone ablation with Er:YAG and CO2 laser: study of thermal and acoustic effects. AB - A pulsed Er:YAG laser at 2.94 microns and a superpulsed CO2 laser at 10.6 microns are used to investigate bone ablation applications in otolaryngology. Quantitative measurements of mass removal and the ablation depth of cat skull bone and rat femur are presented with the Er:YAG laser at fluences of 9-117 J/cm2. Histological results show that the minimal thermal injury zone from the edge of the lesion is 5-10 microns. Comparison of the photoacoustic and thermal effects during the ablation process indicates that the temperature rise from the 10.6-microns light was higher than that from the 2.94-microns light but that the photoacoustic wave amplitude produced with the Er:YAG laser was higher than that with the CO2 laser. The fluence used for the efficient ablation of bone tissues produces a photoacoustic wave ranging from 100 to 120 dB. The ear can tolerate this level for a short time period. Results of this study suggest that the Er:YAG laser can be an important surgical tool in otolaryngology. PMID- 1614268 TI - Holmium:YAG laser ablation of human intervertebral disc: preliminary evaluation. AB - Percutaneous discetomy has become a viable alternative in the treatment of herniated intervertebral disc. This study determined the effectiveness of holmium: YAG laser for ablation of human disc tissue. Human cadaveric intervertebral disc was harvested and stored in cold saline-soaked gauze for evaluation within 24 hr of removal. Using a specially designed apparatus, a 600 microns diameter fiber was advanced perpendicular through the annulus fibrosis at a controlled force of 0.098 Newtons (10 g). Samples were lased in air (n = 17) and in room temperature saline (n = 32). The laser energy was delivered at 5 Hz, 250 microseconds pulsewidth, and from 50 mJ/mm2 to 1,100 mJ/mm2 fluence. Three to six holes were lased using identical parameters in each tissue specimen and were evaluated histologically and by morphometric analysis. The maximum zone of thermal necrosis and thermal denaturation occurred at 700-1,100 mJ/mm2; 140 microns and 590 microns in air and 80 microns and 730 microns in saline, respectively. At fluences between 200 and 700 mJ/mm2, the thermal necrosis ranged from 20 to 60 microns in air and from 10 to 50 microns in saline, the zone of denaturation also being less. The holes created with the 600 microns fiber were circular in shape, with a mean diameter of 500 microns (n = 3). The etch rates (penetration/pulse) appeared to increase with increasing fluences. In saline, the etch rate ranged from 7 to 53 microns/pulse (r = 0.57, P less than or equal to 0.10), and, in air, the values ranged from 7 to 65 microns/pulse (r = 0.79, P less than or equal to 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614269 TI - Techniques for pharmacological and toxicological studies with isolated hepatocyte suspensions. AB - Since its introduction in 1969, the high-yield preparation of isolated hepatocytes has become a frequently used tool for the study of hepatic uptake, excretion, metabolism and toxicity of drugs and other xenobiotics. Basic preparative methods are now firmly established involving perfusion of the liver with a balanced-saline solution containing collagenase. Satisfactory procedures are available for determining cell yields, for expressing cellular activities and for establishing optimal incubation conditions. Gross cellular damage can be detected by means of trypan blue or by measuring enzyme leakage, and damaged cells can be removed from the preparation. Specialized techniques are available for preparing hepatocyte couplets and suspensions enriched with periportal or perivenous hepatocytes. The isolated hepatocyte preparation is particularly convenient for the study of the kinetics of hepatic drug uptake and excretion because the cells can be rapidly separated from the incubation medium. Isolated liver cells have also proved valuable for investigating drug metabolism since they show many of the features of the intact liver. However, they also show important differences such as losses of membrane specialization, some degree of cell polarity and the capacity to form bile. The many consequences of the hepatic toxicity of xenobiotics including lipid peroxidation, free radical formation, glutathione depletion, and covalent binding to macromolecules are also readily studied with the isolated liver cell preparation. A particular advantage is the ease with which morphological changes as a result of drug exposure can be observed in isolated hepatocytes. However, it must be remembered that the isolation procedure inevitably introduces changes that may make the cells more susceptible than the normal liver to damage by xenobiotic agents. Despite its limitations, the isolated hepatocyte preparation is now firmly established in the armamentarium of the investigator examining the interaction of the liver with xenobiotics. PMID- 1614270 TI - Stimulation of melanin synthesis of B16-F10 mouse melanoma cells by bufalin. AB - Bufalin, which is one of prominent components of Chinese toad venom, was found to decrease the rate of cell proliferation of mouse melanoma clone B16-F10 cells and a concomitant stimulation of expression of its melanotic phenotype. The effect of bufalin on melanogenesis included stimulation of tyrosinase activity and increase of cellular melanin content. These effects became apparent after 48 hr exposure to 10(-4) M bufalin and increased thereafter. Other cardiotonic steroids, such as cinobufagin and ouabain, at the concentration of 10(-4) M for 6 days, also showed the stimulatory effect on melanin synthesis of B16-F10 cells, but not digitoxigenin. PMID- 1614271 TI - Studies on lidocaine-induced kindling. AB - Lidocaine HCl, injected 5 times weekly, produces pharmacological kindling in rats. The aims of the present study were to: 1) approximate the threshold dose for the effect in mice and 2) determine if injections given less frequently than 5 times weekly produces kindling. Mice were injected (IP) either 5 times weekly for 4 weeks or 2 times weekly for 10 weeks, with doses ranging from 30 to 50 mg/kg. Kindling was defined as the appearance of convulsions on each of 5 consecutive injections. The estimated threshold dose for kindling was approximately 40 mg/kg, as suggested by the observation that 2 of 8 and 8 of 8 mice were kindled at 40 and 50 mg/kg respectively when injected 5 times each week. Whether mice were injected (50 mg/kg) 5 times weekly, or, only twice weekly, 80% of them were kindled by the fifteenth injection. Thus, it would appear that pharmacological kindling might be as much a function of number of injections as it is of frequency of injections. PMID- 1614272 TI - Intraperitoneal injection of chloral hydrate causes intra-abdominal adhesions and unilateral testicular atrophy in golden Syrian hamsters. AB - We investigated the reason for the high mortality we had observed in hypophysectomized-orchidectomized Golden Syrian hamsters that were anesthetized with intraperitoneal (i.p.) injections of chloral hydrate (CH). Intact male Golden Syrian hamsters were injected intraperitoneally with 0.1cc/100g BW of a 35% solution of CH, a 35% solution of sodium chloride, or double-distilled water. Equal numbers of hamsters in each group were injected on the right or left side of the abdomen. Within 10 days, 35% of the CH-injected hamsters were dead or had to be euthanized. Autopsy revealed severe peritonitis and adynamic ileus. CH injected hamsters that survived gained weight at a rate similar to that of the controls. All surviving hamsters were killed 18 days after the injections. Among the surviving CH-injected hamsters, 84.6% had intra-abdominal adhesions, 61.5% had unilateral testicular atrophy, and 53.8% had a yellowish necrotic mass in the epididymal fat pad (EFP). All the lesions occurred on the side that was injected. The atrophied testes had been rendered cryptorchid due to involvement with intra abdominal adhesions. In the water-treated controls, there were no abnormalities; whereas, in the saline controls, 75% had a mass in the EFP. Histology of the EFP mass was similar in hamsters injected with CH or hypertonic saline and suggested a diagnosis of fat necrosis. The results suggest that the mortality, the intra abdominal adhesions, and the unilateral cryptorchidism were caused by a single i.p. injection of CH, but the fat necrosis in the EFP was probably caused by high concentrations of salt. The results further suggest that high concentrations of CH should not be injected intraperitoneally for anesthesia in chronic studies, particularly of the male reproductive system. PMID- 1614273 TI - Identification of hydropathically complementary putative contact sequences within epidermal growth factor (EGF) and the EGF receptor. AB - Hydropathic complementariness (HC) has been proposed as a novel molecular recognition code for how two proteins can recognize one other and thus form a reversible complex. If a protein contains a segment of a few amino acid residues that is surface-exposed, plus in extended conformation, plus composed of residues whose hydropathy pattern is opposite to that of a correspondingly sized segment on the respective other protein, this protein may bind to the other one through such a segment of HC (1). In order to identify in a pair of proteins sequences of HC we have developed the program PUTATIVE SITES SEARCHER (PSS-1) (2), a name that alludes to the possibility that such a segment of HC could represent a putative contact "site". Here we describe the application of PSS-1 to the study of human epidermal growth factor (EGF) and human EGF receptor (EGF-R). Six segments of HC were identified, two of which, designated a and b, fall exactly into experimentally verified contact regions on EGF as well as on EGF-R. Site a consists of residues 25.AEIYMCV.19 of EGF ("half site" aEGF) and of residues 331.NIKHFKN.337 of the EGF-R ("half site" aEGF-R); site b consists of residues 34.VCNCAY.29 of EGF and residues 365.PQELDI.370 of the EGF-R. Most interestingly, both half sites aEGF and bEGF localize in loop B of hEGF which is recognized as being essential for receptor binding. Similar is true for the half sites aEGF-R and bEGF-R that localize in subdomain III (residues 314-445) of the extracellular part of the EGF-R, also identified to be responsible for EGF binding. Thus, each of the two theoretically predicted sites is composed of half sites whose functional importance is experimentally verified. This correspondence supports the principal suitability of PSS-1 and suggests that EGF binds to EGF-R at least in part by means of HC contacts besides using, most probably, also "classical" (i.e. non-HC-type) contacts (e.g. charge interactions or hydrophobic bonds). PMID- 1614274 TI - Reversible, amine--selective effects of acute and chronic brofaromine treatment in the rat. AB - The effects of brofaromine, clorgyline (reversible and irreversible type A MAO inhibitors, respectively) and tranylcypromine (non-selective MAO inhibitor) on rat striatal levels of phenylethylamine, tryptamine, m-tyramine and p-tyramine were determined. Brofaromine and clorgyline increased m- and p-tyramine levels, but not phenylethylamine levels. Brofaromine given at a dose of 100 mg/kg did increase tryptamine levels. Tranylcypromine increased the levels of all four amines greatly. The effects of chronic treatment with brofaromine on amine levels were not different from those following acute treatment. By contrast, chronic treatment with clorgyline caused greater increases in striatal m- and p-tyramine levels than did acute clorgyline. These data show that changes in the rat striatal levels of m-tyramine and p-tyramine may be used as in vivo indicators of the selectivity and reversiblity of inhibition of type A MAO, while tryptamine levels reflect non-selective inhibition of both types of MAO. PMID- 1614275 TI - Pharmacological evaluation of GS-389, a novel tetrahydroisoquinoline analog related to higenamine, on vascular smooth muscle. AB - The effects of GS-389, a novel tetrahydroisoquinoline analog, on isolated rat and mouse thoracic aorta rings, were investigated. Both GS-389 and papaverine induced endothelium-independent, concentration-dependent relaxations of the rat and mouse aortae precontracted with phenylephrine (PE). The GS-389-induced inhibition of the contractile response to PE was noncompetitive. The initial phasic contraction to PE elicited in Ca(2+)-free media was also attenuated by pretreatment with GS 389, indicating that GS-389 may interfere with the release of intracellular Ca2+ and/or the effects of intracellular Ca2+ release. GS-389 potentiated the vasodilatory effects of isoproterenol and sodium nitroprusside in rat and mouse aortae. GS-389 significantly increased cGMP levels in the rat aorta and inhibited cGMP phosphodiesterase from the rabbit brain. Methylene blue, but not propranolol, inhibited the vasodilatory effect of GS-389. These results suggest that the vasorelaxant effect of GS-389 may be due, at least in part, to inhibition of cGMP metabolism. PMID- 1614276 TI - Effects of concomitant cholinergic and adrenergic stimulation on learning and memory performance by primates. AB - Physostigmine and other centrally-acting acetylcholinesterase inhibitors are currently being examined for their potential in the treatment of Alzheimer's Disease. The ability to employ this class of agents is limited by the potential for debilitating and dangerous side effects. Clonidine and related drugs have recently been demonstrated to enhance memory performance in monkeys. Clonidine also inhibits the function of cholinergic neurons in specific brain regions and reduces certain side effects of physostigmine. Seven adult macaque monkeys performing a delayed matching-to-sample (DMTS) task received regimens of increasing doses of clonidine and physostigmine on separate occasions to determine the 'best dose' of each agent in terms of enhanced memory performance. The best doses were combined as a single administration and performance compared to that using the two drugs alone. The combination regimen of clonidine and physostigmine was more effective than either drug alone in enhancing memory performance. Part of the benefit may have been due to the ability to employ significantly higher doses of physostigmine in the combination regimen. A single injection of the combination resulted in enhanced performance both on the day of administration as well as on the following day. These results are consistent with the ability of clonidine to limit the expression or intensity of certain physostigmine-induced autonomic side effects, while allowing the cognitive beneficial effects of the cholinesterase inhibitor. PMID- 1614277 TI - Digitalis-like compounds in the toad Bufo viridis: tissue and plasma levels and significance in osmotic stress. AB - Digitalis-like compounds (DLC), constituents of animal tissues, are possible regulators of the Na+, K(+)-ATPase implicated in water and salt homeostasis. The distribution of DLC in the toad (Bufo viridis) was determined following methanol extraction and partial purification. DLC highest levels were found in the skin but it was also detected in the plasma and many internal organs. Short term (hours) exposure of the toad to hypertonic shock (1.5% NaCl) induced an increase in plasma osmolarity due to an increase in Na+ and Cl- levels. This treatment induced a transient, three fold, increase of DLC levels in the brain and transient reduction of its levels in the ventral skin. Acclimation of the toads to burrowing conditions for six weeks resulted in an increase in plasma osmolarity due to a large increase in plasma urea with a small increase in ion concentrations. Under these conditions DLC levels in the dorsal skin increased by 100% without alteration of its levels in the plasma, brain and ventral skin. DLC levels in the toad brain of control animals, showed a significant dependence on season, being highest in the summer and lowest in the winter. DLC levels in the skin peaked in May while the levels in the plasma were season independent. The changes in DLC levels induced by the short- as well as long-term perturbations in the animal environmental salinity together with the seasonal differences suggest that DLC in the toad is involved in water and salt homeostasis of these animals, but may also participate in other unknown functions. PMID- 1614278 TI - Changes in hepatic lipid composition after infection by LP-BM5 murine leukemia virus causing murine AIDS. AB - The severe hepatic disorders in patients with acquired immune deficiency syndrome (AIDS) is often attributed to a variety of other factors which could affect hepatic function. To evaluate the mechanism of liver damage in murine AIDS induced immune-suppressed animal, a murine model of AIDS (MAIDS), caused by infection with LP-BM5 murine leukemia virus was used at a late stage of the disease. Retroviral infection significantly increased hepatic cholesterol, triacylgycerol and the cholesterol/phospholipid ratio. Similarly, the proportions of palmitic, palmitoleic, linoleic, ratios of linoleic to arachidonic and saturated to unsaturated fatty acids were significantly lower while the proportion of oleic, docosatetraenoic and docosahexenoic fatty acids were significantly increased in the retrovirus infected mice. Hepatic dysfunction as evidence by increased serum transaminase levels were also observed in the retrovirus infected animals. The data suggest that the liver damage in murine AIDS is induced by retroviral infection and the desaturase enzymes system necessary to maintain regular balance of the fatty acids in the cells may be affected during retroviral infection. PMID- 1614279 TI - Characterization of the heredity of kininogen deficiency in brown Norway Katholiek strain rats. AB - Brown Norway rat strain has been studied for mode of inheritance of its congenital deficiency in plasma high molecular weight (HMW)-kininogen and low molecular weight (LMW)-kininogen, and low plasma level of prekallikrein. We examined the genetics of the deficiency by performing a mixed breeding experiment between B/N-Katholiek (B/N-Ka, deficient) and B/N-Kitasato (B/N-Ki, normal) strains. Incidence of the deficiency was judged by the plasma level of HMW kininogen. Plasma level of HMW-kininogen was around 50% of the normal level in all F1 generations of the hybrid between male B/N-Ka and female B/N-Ki (Exp. 1), and between female B/N-Ka and male B/N-Ki (Exp. 2). Incidence of deficiency (plasma HMW-kininogen level less than 5%) in Exp. 1 was 23.8% in male F2 and 20.0% in female F2 generations. By Exp. 2 also the incidence was 25.0% in male and 30.0% in female F2 generations. There was no significant difference of the incidence between the two experiments or sexes. These results indicate the inheritance of the kininogen-deficiency to be Mendelian autosomal recessive, the same as for the reported cases of human kininogen deficiency. Gel filtration study suggests that prekallikrein in the B/N-Ka plasma may be free form, while that in the B/N-Ki plasma may form complex with HMW-kininogen. PMID- 1614280 TI - Erythropoietin induced transmembrane calcium influx in essential hypertension. AB - The effects of erythropoietin (EPO) on cytosolic free calcium concentration ([Ca2+]i) in platelets of 20 essential hypertensive patients (HT) and of 25 normotensive subjects (NT) were investigated using the fura2 technique. In resting platelets [Ca2+]i were not significantly higher in HT compared to NT (74.3 +/- 7.8 nM vs 59.8 +/- 7.0 nM, mean +/- SEM). Addition of EPO significantly increased [Ca2+]i in HT compared to NT (13.8 +/- 5.3 nM vs 0.9 +/- 1.9 nM, p less than 0.01). EPO increased the amount of calcium in intracellular stores. This was confirmed independently using thrombin-induced changes of [Ca2+]i in a calcium free medium and using chlorotetracycline as a marker of stored calcium. After preincubation with EPO thrombin-induced changes of [Ca2+]i were significantly lower in HT compared to NT (306.1 +/- 30.0 nM vs 407.7 +/- 35.7 nM, p less than 0.05). In a calcium-free medium after preincubation with EPO thrombin-induced changes of [Ca2+]i were significantly lower in HT compared to NT (54.7 +/- 11.8 nM vs 100.9 +/- 10.5 nM, p less than 0.05) indicating lower storage capacity in HT. It is concluded that elevated response to EPO may provide a powerful tool to evaluate diagnosis and underlying pathophysiological mechanisms in essential hypertension. PMID- 1614281 TI - 4-Iodotomoxetine: a novel ligand for serotonin uptake sites. AB - The tomoxetine analog, R-4-iodotomoxetine, binds in vitro to a single site of rat cortical membranes with high affinity (Kd = 0.03 +/- 0.01 nM, n = 4) and can be blocked by a selective serotonin reuptake site inhibitor, paroxetine. The [125I]R 4-iodotomoxetine binding at equilibrium is saturable and is temperature- and Na(+)-dependent. The number of specific [125I]R-4-iodotomoxetine binding sites (Bmax = 356 +/- 20 fmol/mg protein) is similar to that of [3H]citalopram (329 +/- 30 fmol/mg protein), a known serotonin uptake inhibitor. The binding of [125I]R-4 iodotomoxetine is selectively inhibited by several serotonin uptake blockers, and a good correlation is demonstrated between the potency of various drugs to inhibit in vitro binding of [125I]R-4-iodotomoxetine and [3H]citalopram. In addition, lesions performed with the neurotoxin p-chloroamphetamine, which destroys monoamine neurons, including serotonergic neuronal system, result in a 90% reduction of [125I]R-4-iodotomoxetine binding when compared to sham controls. These results indicate that the binding sites labeled by [125I]R-4-iodotomoxetine are associated with the neuronal serotonin uptake sites. However, the in vivo and ex vivo results do not show regional localization corresponding to the distribution of serotonin uptake sites. The nonspecific uptake may be related to this compound's high lipophilicity (octanol-buffer partition coefficient = 1100 - 1400 at pH 7). Although the in vivo properties of [125I]R-4-iodotomoxetine make it an unlikely candidate for mapping serotonin uptake sites with SPECT, the high affinity and selectivity should make it a useful tool for in vitro studies of the serotonin uptake sites. PMID- 1614282 TI - Carbamazepine produces nonspecific effects on cocaine self-administration in rats. AB - Anecdotal evidence in humans suggest that carbamazepine suppresses cocaine induced rush and craving. Such claims are unsupported in controlled trials using a placebo control. In the present study, rats were trained to self-administer i.v. cocaine in daily 2-hr sessions in which every tenth lever press delivered 1 mg/kg cocaine. After responding was stable, they were injected before each session with the vehicle for 2 days followed by carbamazepine for 2 days. At a 7 mg/kg dose, carbamazepine was without effect, whereas 15 mg/kg suppressed responding for cocaine only on the second (day 4) day of carbamazepine treatment. With 4 consecutive days of treatment, carbamazepine (15 mg/kg) reduced cocaine maintained responding slightly, but significantly. In another group of animals trained to lever-press for food reinforcement, carbamazepine (15 mg/kg) also significantly decreased the rate of responding, suggesting that the suppression of responding was not specific to cocaine-reinforced behavior. PMID- 1614283 TI - Quantitative analytical mass spectrometry of endogenous neuropeptides in human pituitaries. AB - This manuscript reviews state-of-the-art mass spectrometric (MS) methodology for the qualitative (amino acid sequence determination) and quantitative analysis of opioid neuropeptides in human pituitary tissue. Those analytical data are required for the elucidation of the basic molecular mechanisms involved in tumor formation and to test the hypothesis that metabolic defects in neuropeptidergic system processing is a contributing factor to human anterior pituitary tumor formation. Several different neuropeptide products that derive metabolically from the proenkephalin A and proopiomelanocortin (POMC) precursors have been analyzed separately and together in human pituitaries, including post-mortem controls and post-surgical tumors. The quantification, with optimal molecular specificity, of a peptide in a tissue is an important measurement because the amount of an endogenous peptide reflects the ratio of its synthesis to its degradation and thus, any defects in those processes may be reflected in the amount of a peptide. PMID- 1614284 TI - An EEG analysis of drug effects after mild head injury in mice. AB - An electroencephalographic (EEG) and behavioral model of head injury in unanesthetized, free moving mice has been used to test the effects of TRH and GM1. In our experimental conditions a mechanical head injury capable of inducing loss of righting reflex for 2 to 60 sec, also induces a consistent decrease of the total power of the spectrum of EEG and a decrease of the power of fast beta band (20-40 Hz) for at least 120 min. TRH, injected after trauma in dose of 10 mg/kg, caused improvement of EEG total power of the spectrum. GM1 in high (30 mg/kg) but not in low dose (5 mg/kg) caused more rapid restoration of both the total power and fast as well as slow beta band power. These results suggest that GM1 has favorable effects on post-concussive neurophysiological symptoms in head injured animals. PMID- 1614285 TI - Comparative effects of Des Leu Angiotensin I and Angiotensin II on AVP secretion from the hypothalamoneurohypophysis and pituitary of the rat. AB - In the present study we compared the effects of Des Leu Angiotensin I (Des Leu AI) with Angiotensin II (AII) on the secretion of vasopressin (AVP) from the isolated hypothalamoneurohypophyseal system (HNS) and isolated posterior pituitary gland of the rat. Administration of 10(-6)M, 10(-5) M and 10(-4) M Des Leu AI was without significant effect on AVP secretion from the HNS. A similar phenomenon was seen in the posterior pituitary with 10(-6) M and 10(-5) M Des Leu AI, although 10(-4) M significantly increased AVP release. Administration of 10( 6) M AII was without significant effect in either preparation, although 10(-5) M and 10(-4) M AII caused significant dose-dependent increases in AVP secretion over control release that were similar in both the HNS and posterior pituitary gland. These results suggest that Des Leu AI is not a physiologically relevant stimulus of AVP secretion when restricted to this area of the rat brain. They are also consistent with the presence of receptors sensitive to AII in the pituitary gland of the rat. PMID- 1614286 TI - The role of cyclo-oxygenase and lipoxygenase in the interleukin-1-induced activation of the HPA axis: dependence on the route of injection. AB - Interleukin-1 (IL-1) has been shown to activate the hypothalamic-pituitary adrenal (HPA) axis, and to elevate cerebral concentrations of tryptophan and the norepinephrine catabolite, 3-methoxy,4-hydroxyphenylethyleneglycol (MHPG). Eicosanoids have been shown to be involved in a number of the effects of IL-1, but their role in the activation of the HPA axis is controversial. We studied the effects of various cyclo- and lipoxygenase inhibitors on the neurochemical and HPA responses to IL-1. Pretreatment of mice with the cyclo-oxygenase inhibitors, indomethacin (10-25 mg/kg) or ibuprofen (10 mg/kg) failed to prevent the elevations of plasma corticosterone, or hypothalamic MHPG or tryptophan that followed intraperitoneally (IP) administered IL-1. Similar results were obtained with the nonspecific oxygenase inhibitor, BW 755C, and the lipoxygenase inhibitor, BW A4C. However, the cyclo-oxygenase inhibitor, diclofenac, did attenuate the IL-1-induced elevation of plasma corticosterone and the neurochemical changes. To resolve the conflicting data on the effect of indomethacin on the IL-1-induced elevation of plasma concentration, we studied the effects of indomethacin on the response to IL-1 injected intravenously (IV). By contrast with the response to IP IL-1, that to IV IL-1 was attenuated by indomethacin. Time course of the HPA response to IL-1 is more rapid following IP injections than IV, therefore we assessed the effects of IV IL-1, earlier than that to IP IL-1. Forty min following IP IL-1, the corticosterone response to IL-1 was markedly attenuated. This suggests that more than one mechanism is involved in the HPA response to IL-1. The more rapid one, predominant in the case of IV injections, is sensitive to cyclo-oxygenase inhibitors, whereas the slower one is not. PMID- 1614287 TI - Changes in plasma free and sulfoconjugated catecholamines before and after acute physical exercise: experimental and clinical studies. AB - To elucidate whether sulfoconjugated catecholamines in plasma, especially dopamine, serve as a source of free catecholamines, we examined the change in afterload on the deconjugating activity of catecholamines in isolated Langendorff perfused rat hearts. Dopamine-sulfate was administered under ordinary or high work-load conditions. Free dopamine in the effluent was increased by the high work-load of the hearts, whereas conjugated dopamine showed an apparent decrease. These results indicate the possibility that deconjugation of sulfoconjugated catecholamines is accelerated by a high-work-load. To obtain further evidence in humans, we also examined the changes in the plasma levels of free and sulfoconjugated catecholamines in healthy volunteers before and after marathon running. Free dopamine increased 1.99-fold from the baseline value after exercise, whereas conjugated dopamine decreased by 12%. Similarly, the plasma levels of free noradrenaline and adrenaline increased after exercise to 2.45- and 1.51-fold their respective baseline values, while conjugated noradrenaline and adrenaline both decreased. These clinical results, as well as those of the experimental studies, suggest that the increase in plasma free catecholamines after exercise is due not only to increased release from the sympathoadrenal system but also to accelerated conversion from sulfoconjugated catecholamines in the plasma. PMID- 1614288 TI - Blockers of potassium current and resting membrane potential in rat muscle fibers. AB - Rat diaphragm fibers were equilibrated for several hours in 150 mM KCl; when they were returned to 5 mM KCl the resting potential went back to its original level with a half time of 17 min. This repolarization was blocked by 5 mM BaCl2, a blocker of the inward rectifier K channel. On the other hand, 0.1 mM apamin and 0.02 mM glibenclamide which block the Ca-dependent and ATP sensitive K channels, respectively, and 0.1 mM 9-AC a blocker of the Cl- channel did not affect the repolarization. 5 mM barium decreased the K conductance measured under current clamp conditions in diaphragm muscle fibers. The possible role of the inward rectifier system in the repolarization following return to normal [K]o is discussed. PMID- 1614289 TI - Antimony and Cleopatra. PMID- 1614290 TI - Endogenous ouabain: implications for cardiovascular disease diagnosis and therapy. PMID- 1614291 TI - The role of ionized cytosolic calcium ([Ca2+]i) in injury and recovery from anoxia and ischemia. PMID- 1614292 TI - The supportive care unit--inpatient geriatric rehabilitation: preliminary data. PMID- 1614293 TI - Unusual articular manifestations in chronic renal disease. PMID- 1614294 TI - Hemoglobin as oxygen carrier in cell-free fluids. AB - The University of Maryland is studying the oxygen needs of internal organs and how these needs can be met by oxygen carriers in cell-free fluids. Once developed, cell-free oxygen carriers will have a large variety of applications including hemodilution, transfusion therapy, organ preservation, and cancer therapy. PMID- 1614295 TI - A new concept of hemorrhagic shock: implications for therapy. PMID- 1614296 TI - The importance of measuring microalbumin. PMID- 1614297 TI - Violence in the Accident and Emergency Department. AB - Crimes of violence are recorded increasingly frequently, including those involving health professionals. We reviewed records of violent incidents kept for a major Accident and Emergency Department over a ten-year period. Details were recorded in a Violent Incident Book by all grades of A/E staff, and separate records were kept by hospital security officers. A total of 407 incidents were recorded. Numbers, rank and sex of staff assaulted, types of assault, injuries received, weapons used and characteristics and disposal of perpetrators were recorded. Many were young males who had been drinking: others were regular attenders, of whom three subsequently died and one convicted of murder. Nurses and male doctors appeared to be at the greatest risk of assault and receptionists at the least risk. Recording of violent incidents and subsequent prosecution seemed inconsistent, and may have reflected the lack of a code of practice in this area. Suggestions are made about preventing, predicting and dealing with violence, and its aftermath, in the A and E department, including the use of security officers and closed circuit television, waiting room design, the recognition of body language and signs of alcohol or substance intoxication. The importance of staff support after an assault is emphasized, including immediate and long-term counselling, provision of legal advice, criminal or civil court action, victim support schemes and the workings of the Criminal Injuries Compensation Board. Free legal advice for staff assaulted at work should be included in the terms of service of NHS staff. PMID- 1614298 TI - Injuries due to violent crimes. AB - This is a study of police reported assaults during 1979, 1982 and 1985 in the County of Kopparberg. Criminological and odontological variables of 1,870 cases of assaults reported to the police during these three separate one-year periods were collected and analysed. Most of the cases were from densely populated areas. There was an increase in cases from 1979 to 1985, particularly of violence in residences. No differences in the type or kind of assault could be found. The proportion of women victims increased markedly and, to a lesser extent, so did the proportion of women offenders. One third of the victims were not injured by the assault, one third suffered haematomas or swellings and one third suffered wounds. 6.5 per cent of the total had fractures. The left side of the face was the most common site of soft-tissue injuries and zygomatico-orbital fractures. No aggravation of the violence or the resultant injuries could be found during these periods. PMID- 1614299 TI - Common poisons in Singapore--past and present. AB - A study on past toxicological activities in Singapore enabled us to capture the trends of poisons abused in this country over the last 108 years. Until the early sixties, corrosive alkali and acids, alcohol (poisoning cases), inorganic chemicals, heavy metals and plant alkaloids were the mainstay of poisons principally used. The seventies and eighties saw a swing towards pharmaceuticals. The 1988-89 data gave alcohol (poisoning cases), pharmaceuticals, household items such as detergents, hypochlorite and antiseptic, carbon monoxide, paraquat, malathion, organic solvents (toluene and xylenes) and narcotics as the mainstay of poisons encountered. The last two classes of poisons reflect the continuing problems of glue sniffing and narcotics abuse facing Singapore. PMID- 1614300 TI - Fatal self-induced hyperinsulinaemia: a delayed post-mortem analytical detection. AB - The inconspicuous number of cases of self-induced hyperinsulinaemia reported in the literature may suggest that many are obscure enough to escape their detection. A case of fatal suicidal hyperinsulinaemia in a non-diabetic is reported here, and in whom only a retrospective biochemical analysis provided an explanatory cause of death. A quantitative radioimmuno assay (RIA) estimation of the refrigerated postmortem blood sample stored at 4 degrees C for three weeks gave a positive insulin yield. It reiterates the need, in forensic cases, for a very low threshold of suspicion and a good back-up for the appropriate body fluid analysis or tissue microexamination, especially when full details of the circumstances surrounding the death are not available at the autopsy. A brief resume on insulin is presented as a background to the current forensic interest in the apparent increase in sudden deaths in young diabetics amidst the controversy about the bio-designed 'human' insulin and subjective unawareness of severe hypoglycaemia. PMID- 1614301 TI - Epilepsy and criminal law. AB - Automatic episodes of aggressive or violent behaviour may occur during or after an epileptic fit. Epileptic automatisms are regarded by the law as 'insane automatisms'. A person who commits a crime during the course of a seizure is therefore legally insane and must be committed to a psychiatric hospital. The law of insanity is inappropriate when applied to epileptic automatisms. A change in the law is therefore necessary to remove epileptic offenders from the legal ambit of insanity, and to save them the threat of detention in a mental hospital as a consequence of their crime. PMID- 1614302 TI - Setting up psychiatric liaison schemes to magistrates' courts: problems and practicalities. AB - Guidelines are set out to aid those wishing to establish psychiatric liaison services to magistrates' courts, as recommended by the Home Office. The account is based upon 20 months' experience of running such a scheme at Clerkenwell magistrates' court in inner London. The practical problems in initiating such a service are explored together with difficulties likely to be encountered in its running. These include questions of personnel, interviewing facilities, relations with other disciplines, legal issues concerning the Mental Health Act and problems encountered in negotiating with catchment area services. Suggestions are given as to how difficulties may be overcome. The future of liaison schemes to magistrates' courts is discussed. PMID- 1614303 TI - Sleepwalking and indecent exposure. PMID- 1614304 TI - 'How dangerous is it that this man goes loose!' (Hamlet Act 4 Scene III) PMID- 1614305 TI - The right of silence. PMID- 1614306 TI - Causes celebres. The Thomas Lund Lecture, delivered to the British Academy of Forensic Sciences on Tuesday 22 October 1991. PMID- 1614307 TI - Correlations between in vivo 31P MRS measurements, tumor size, cell survival, and hypoxic fraction in the murine EMT6 tumor. AB - Phosphorus metabolite ratios were measured using 31P magnetic resonance spectroscopy shortly before measurement of cell survival and radiobiologic hypoxic fraction (HF) in EMT6/SF tumors, transplanted into a hindlimb of Balb/c mice. A total of 58 tumors with a volume range of 180 to 1250 mm3 were examined in experiments entailing no anesthesia. Postirradiation tumor cell viability was measured using an in vitro clonogenic assay. Correlations between tumor volume, surviving fraction (SF), HF, phosphorus metabolite ratios, and intracellular pH were computed. Both SF and HF increased significantly with tumor volume as did the metabolite ratios of inorganic phosphorus and phosphomonoesters to nucleoside triphosphates (Pi/NTP and PME/NTP, respectively), as well as Pi to phosphocreatine (Pi/PCr). In comparison to HF, the ratios of Pi/NTP, Pi/PCr, and PME/NTP each yielded significant positive correlations (Kendall correlation coefficients(tau) = 0.25 to 0.33). However, these were not significantly stronger than the correlation between HF and volume (tau = 0.21). Apparent values of tumor pH did not correlate with any other measured parameter. While these results indicate a statistical relationship between HF and the measured metabolite ratios, the widely scattered data, as reflected by magnitude of tau less than 0.35, made metabolite ratios poor predictors of HF in individual tumors. PMID- 1614308 TI - Analysis of encoding efficiency in MR imaging of velocity magnitude and direction. AB - The efficiency of balanced versus unbalanced techniques for phase-angle-based velocity magnitude and direction imaging is investigated. Methods having balanced flow-encoding gradients (gradients in positive and negative directions with a zero center of gravity) are compared with unbalanced methods. For three dimensional imaging, a currently used balanced method is the six-point technique having opposed gradients pairs for each orthogonal direction. A currently used unbalanced method is a four-point null technique which has three orthogonal gradients and an additional acquisition having no specific flow encoding to correct the baseline (null) phase. In the gradient-limited case of slow flow and perfusion, the balanced method is predicted to have higher velocity magnitude-to noise ratio per time (SNRV) by a factor of 1.63, with similar results for velocity direction. In the wraparound-limited case of faster flows and motions, similar results are found when a null acquisition is added to the balanced method. This results in a seven-point balanced method having an SNRV 1.51 times that of the four-point unbalanced method. If null phases are within the [ pi/2,pi/2] interval, this additional null acquisition is unnecessary. Other four point methods are also considered. These results indicate that, in general, balanced methods have advantages over unbalanced methods for velocity imaging. PMID- 1614309 TI - Application of self-refocusing band selective RF pulses for spectroscopic localization. AB - A new self-refocusing slice selection 90 degrees pulse is presented and its incorporation in the SPACE localization sequence described. Experimental comparisons are made with the self-refocusing pulse reported by Geen (H. Geen, S. Wimperis and R. Freeman, J. Magn. Reson. 85, 620 (1990)). The main source of localization error in the SPACE sequence is traced to the hard pi/2 pulse and the development of a shaped-pulse version of the sequence is described. This required the calculation of a slice-selective pulse capable of rotating coherent transverse magnetization to the z-axis. The RF power requirements for these experiments are also discussed. PMID- 1614310 TI - Metabolic response of the human heart to inotropic stimulation: in vivo phosphorus-31 studies of normal and cardiomyopathic myocardium. AB - In order to determine if an increase in myocardial oxygen consumption is accompanied by changes in high energy phosphates in normal subjects and patients with dilated cardiomyopathy, phosphorus-31 spectra were acquired under resting conditions and during dobutamine infusion. In seven normal subjects, dobutamine raised the rate-pressure product to 226% of control. The ratio of PCr/ATP was 1.86 +/- 0.17 (mean +/- SE) under resting conditions and 1.90 +/- 0.22 (P = 0.44) with dobutamine infusion. In eight patients with dilated cardiomyopathy, dobutamine raised the rate-pressure product to 161% of control. As in the normal subjects, the ratio of PCr/ATP under resting conditions (1.63 +/- 0.24) was unchanged during dobutamine infusion (1.57 +/- 0.24, P = 0.38). These data indicate that increases in cardiac work do not have a major effect on high energy phosphate concentrations in normal subjects or in patients with clinically compensated dilated cardiomyopathy. PMID- 1614311 TI - NMR studies of erythrocytes immobilized in agarose and alginate gels. AB - 31P and 13C NMR were used to study the energy metabolism in perfused, human erythrocytes. The erythrocytes were immobilized in agarose threads, Ca- or Ba alginate beads, and Ba-alginate-coated agarose threads. Erythrocytes were easily washed out from the agarose threads, but not from alginate-containing gels. Various small molecules, such as hypophosphite, dimethyl methylphosphonate, and methylphosphonate, were taken up from the perfusion medium in a normal manner. In addition, the 2,3-bisphosphoglycerate (2,3-DPG) chemical shifts were sensitive to the oxygen partial pressure suggesting that O2 molecules were diffusing through the gel and modifying the binding of 2,3-DPG to hemoglobin. A combination of inosine and pyruvate stimulated the synthesis of 2,3-DPG, but only if inorganic phosphate was present in the perfusion medium. Inosine only resulted in a dramatic rise in the intracellular sugarphosphate concentrations. Furthermore, [2 13C]glucose was converted to [2-13C]lactate by immobilized cells at a rate which was comparable to that in a control suspension. In summary, immobilization in Ba alginate-coated agarose threads was an efficient way of trapping human erythrocytes for whole cell NMR investigations. PMID- 1614312 TI - Chemical shift imaging with phase-encoding RF pulses. AB - An inherent problem of conventional chemical shift imaging is signal contamination into adjacent voxels. This is especially severe in proton spectroscopy of the central nervous system, where the lipid signal from the skull is several orders of magnitude higher than the metabolite resonances from the brain. The reason for the contamination lies in the fact that the distribution of spins does not coincide with the discrete sampling matrix of the discrete Fourier transformation if a continuous phase-encoding scheme using magnetic field gradients is being used. This problem can be overcome if phase encoding is performed by appropriately phase-modulated RF pulses. It is demonstrated that contamination free spectra can be acquired from voxels immediately adjacent to the skull. Using small voxels of 1 x 1 x 2-ml regional variations of N-acetyl aspartate in the cerebellum of patients with oligopontine cerebellar atrophy could be observed. PMID- 1614313 TI - Elimination of oblique flow artifacts in magnetic resonance imaging. AB - We present an analysis of how flow oblique to the frequency-encoding direction generates displacement artifacts in MR imaging and show that for flow which has constant velocity between the start of the phase encoding and the center of the echo it is possible to eliminate these artifacts by gradient moment nulling in the phase-encoding direction. However, unlike the standard moment nulling calculations for flow compensating the frequency-encode and slice-selection gradients, the phase-encoding first moment must be nulled specifically with respect to the echo center. Limitations of this method imposed by finite gradient strengths are analyzed. In 3D volume acquisitions with two axes phase encoded it is possible to correct for oblique flow in all directions, and this is demonstrated in images of a human volunteer. Correction for oblique flow displacement artifacts may be particularly useful in quantitative flow and angiographic applications. PMID- 1614314 TI - In vivo 7Li NMR imaging and localized spectroscopy of rat brain. AB - Lithium-7 in vivo NMR spectroscopy and imaging techniques have been developed at 4.7 T for rat head. The pharmacokinetics of lithium (Li) uptake in rat head has been measured using STEAM localized spectroscopy for the whole brain, which showed relatively rapid uptake of Li and a steady level of Li from about 5 to 20 h. Localized spectroscopy on brain sections revealed no differences in Li concentration among the front, middle, and rear of the brain. The spin-lattice relaxation time showed a single exponential decay for the head. The spin-spin relaxation time for head showed a biexponential behavior. Using a 1H-7Li double coil assembly, 7Li images were generated for rat head, as was the corresponding 1H image for anatomic localization. The 7Li image (7-mm slice thickness, 4-mm in plane resolution) recorded after the last dose in a multiple ip dose protocol shows the Li distribution in the head and neck. Based on 7Li images, the Li level in muscle was about twice that in the brain. Variations of 7Li intensity level across the brain were typically small. PMID- 1614315 TI - Deblurring for non-2D Fourier transform magnetic resonance imaging. AB - For several non-2D Fourier transform imaging methods, off-resonant reconstruction does not just cause geometric distortion, but changes the shape of the point spread function and causes blurring. This effect is well known for projection reconstruction and spiral k-space scanning sequences. We introduce here a method that automatically removes blur introduced by magnetic field inhomogeneity and susceptibility without using a resonant frequency map, making these imaging methods more useful. In this method, the raw data are modulated to several different frequencies and reconstructed to create a series of base images. Determination of degree of blur is done by calculating a focusing measure for each point in each base image and a composite image is then constructed using only the unblurred regions from each base image. This method has been successfully applied to phantom and in vivo images using projection reconstruction and spiral-scan sequences. PMID- 1614316 TI - Improving resolution in MRI by interleaving data acquisition for increased digitization rates. AB - In certain situations in magnetic resonance imaging the digital resolution in the frequency encode direction may be compromised by hardware limits on data digitization rates. We demonstrate a method of overcoming this restriction, without hardware modifications, by interleaving data from several acquisitions to produce a higher resolution composite data set. PMID- 1614317 TI - Experimental analysis of T1 imaging with a single-scan, multiple-point, inversion recovery technique. AB - Look and Locker's single-scan, multiple-point, T1 determination technique modified for imaging applications was evaluated experimentally for its accuracy and reliability with respect to the pulse sequence parameters, in particular, to the interpulse delay, tD, and the tip angle, alpha. T1 imaging experiments were performed with a 0.5-T imaging system on a phantom which consisted of an array of vials containing 2% agarose gels doped with various amount of Mn2+ using different combinations of the parameter set (tD, alpha). T1 results obtained with this technique were compared with those measured by a conventional inversion recovery procedure using the same spectrometer. Strategic choice of pulse sequence parameters to minimize experimental errors and the criteria for these choices will be discussed. PMID- 1614318 TI - MR imaging of brain surface using steady-state free precession. AB - We present an imaging technique that affords direct and noninvasive visualization of brain surface structure. This technique utilizes the signal before the rf pulse in steady-state free precession. This signal highly reflects the spin-spin relaxation time T2 as was studied in our laboratory (Matsui et al. J. Magn. Reson. 62, 12, 1985). Therefore the cerebrospinal fluid (CSF), having a long T2, is depicted as high intensity. The CSF permeates cerebral sulci and fissures. The imaging time with this technique is less than 1 min. PMID- 1614319 TI - Hadamard spectroscopic imaging technique as applied to study human calf muscles. AB - In vivo results obtained by the B1 insensitive Hadamard spectroscopic imaging multivolume technique used with a surface coil are shown. The functional behavior of different human calf muscles during exercise was determined and the Pi/PCr ratio in each calf muscle, during steady-state conditions, was measured as a function of work level. Different levels of metabolic and physical activity were observed at the three calf muscles. PMID- 1614320 TI - 31P NMR studies of resting zone cartilage from growth plate. AB - 31P NMR of superfused resting cartilage demonstrated the presence of phosphocreatine in chondrocytes. Changes in pH and in the NTP level were followed during carbon source starvation. From 31P spectra of perchloric acid extracts, phosphoethanolamine, phosphocholine, and the corresponding glycerol diesters were identified as the major phosphomonoester and phosphodiester components. PMID- 1614321 TI - Measurement of brain perfusion by volume-localized NMR spectroscopy using inversion of arterial water spins: accounting for transit time and cross relaxation. AB - The theoretical model for perfusion measurement by NMR using arterial labeling of endogenous water is extended to include the effects of transit time and cross relaxation of tissue water with macromolecules. Water magnetization in rat brain is monitored using the STEAM method to simultaneously determine the transit time, magnetization transfer rate constant, and perfusion. The results show that the transit time in rat brain is quite short, and thus its effect on perfusion measurement is small. It is also demonstrated both theoretically and experimentally that the steady-state effects of cross-relaxation with macromolecules on perfusion measurement are accounted for by a proper control experiment. PMID- 1614322 TI - Magnetization transfer time-of-flight magnetic resonance angiography. AB - Time-of-flight (TOF) angiography based on inflow enhancement is limited by the steady-state signal differences between blood and the surrounding stationary tissues. We present a new TOF sequence in which magnetization transfer contrast is used to supplement wash-in effects. Angiograms demonstrating the superior performance of this technique are presented. PMID- 1614323 TI - An aqueous gastrointestinal contrast agent for use in echo-planar MR imaging. AB - Four volunteers were imaged with echo-planar imaging before and after ingesting a dilute barium preparation. The contrast material improved bowel visibility by increasing lumen signal intensity, without increasing noise. Long T2 gastrointestinal contrast material can be used in T2-weighted imaging when motion artifacts are suppressed by ultrashort acquisitions. PMID- 1614324 TI - Time course EPI of human brain function during task activation. AB - Using gradient-echo echo-planar MRI, a local signal increase of 4.3 +/- 0.3% is observed in the human brain during task activation, suggesting a local decrease in blood deoxyhemoglobin concentration and an increase in blood oxygenation. Images highlighting areas of signal enhancement temporally correlated to the task are created. PMID- 1614325 TI - Contribution of cytoplasmic polypeptides to the 1H NMR spectrum of developing rat cerebral cortex. AB - In the present study the contribution of cytoplasmic polypeptides thymosins beta 4 and beta 10 to the 1H NMR spectrum during the maturation of the rat cerebral cortex was assessed. In the proton spectrum intense broad peaks at 0.9, 1.22, and 1.40 ppm from thymosins decreased in size relative to the signal at 2.02 ppm in parallel to the reciprocal increase in the concentration of N-acetyl aspartate. Levels of thymosins beta 4 and beta 10 were under developmental regulation. It is concluded that peaks from thymosins may provide extended information for an NMR spectroscopist and thus they have to be taken into account in the interpretation of the newborn cerebral 1H NMR spectrum. PMID- 1614326 TI - Noise correlation exists for independent rf coils. PMID- 1614327 TI - The difference in the lcrV sequences between Y. pestis and Y. pseudotuberculosis and its application for characterization of Y. pseudotuberculosis strains. AB - We have sequenced the lcrGVH operon from Y. pseudotuberculosis plasmid pYV995 and compared its sequence with that of Y. pestis. The sequences were highly homological, however, six base pair substitutions were found in one short 14 bp region termed variable sequence. Two oligonucleotides corresponding to variable sequence of Y. pestis (pes-V) or Y. pseudotuberculosis (ptb-V) were synthesized and were used as molecular probes in hybridization experiments with sets of Y. pestis and Y. pseudotuberculosis strains. All 17 Y. pestis strains tested were positive only with the pes-V probe, 18 of 21 Y. pseudotuberculosis strains were positive with the ptb-V probe, while three Y. pseudotuberculosis strains reacted with the pes-V probe but not the ptb-V probe. The 200 bp fragment including variable sequence was sequenced in seven Y. pseudotuberculosis strains. The Y. pseudotuberculosis strains which were positive with the pes-V probe possessed the 200 bp fragment sequence almost identical with that from Y. pestis. No correlation between the Y. pestis-like lcrV sequence and virulence was found for these strains. Moreover, the Y. pseudotuberculosis strains with Y. pestis-like sequences in contrast to Y. pestis possessed unaltered yadA gene. However, we have found the yadA frameshift mutation characteristic for Y. pestis in one Y. pseudotuberculosis strain 312. PMID- 1614328 TI - Analysis of Yersinia pestis chromosomal determinants Pgm+ and Psts associated with virulence. AB - The ability to absorb exogenous pigments (Pgm+) has, until now, been considered an established virulence factor of Yersinia pestis, the causative agent of plague. This property correlates with the sensitivity to the bacteriocin pesticin (Psts). Both functions are chromosomally encoded. In the present study, using Hfr donors and isogenic Pgm-Psts and Pgm-Pstr mutants, these functions were shown to be determined by discrete but closely linked genes. These markers designated pgm and psn, respectively, were preliminarily located within a linkage group including 11 loci. It was also found that pigmentation is not essential for mouse virulence but is necessary for survival of Y. pestis in the flea, the plague vector. At the same time, conversion of an avirulent Pstr mutant to pesticin sensitivity restored some degree of virulence. PMID- 1614329 TI - Isolation and replication in human fibroblast cells (MRC-5) of a microsporidian from an AIDS patient. AB - Many parasitic opportunistic infections occur in AIDS patients. In a young female drug abuser, HIV-positive at the IV stage, a microsporidian was detected and identified in urine by cell culture in fibroblast monolayers (MRC-5) and formally recognized by electron microscopy. This parasite has been involved in hepatitis, myositis and malabsorption syndromes in AIDS patients. Its diagnosis is difficult and this is the first time that its replication has been reported in human diploid cells in vitro. PMID- 1614330 TI - Activated mouse macrophages kill Entamoeba histolytica trophozoites by releasing reactive nitrogen intermediates. AB - Mouse macrophages activated by gamma interferon (IFN-gamma) and bacterial lipopolysaccharide (LPS) are highly cytotoxic for the enteric protozoan parasite Entamoeba histolytica. Herein, we show that this killing by activated macrophages is L-arginine dependent, inasmuch as it was blocked by exogenous arginase or NG monomethyl-L-arginine. These two inhibitors had no effect on E. histolytica cytolytic activity against L929 fibroblasts. Also, macrophage killing of E. histolytica always correlated with nitrite presence in the supernatant fluids. Finally, it was shown that addition of excess iron or the reductant sodium dithionite to activated macrophages blocked their ability to kill E. histolytica. Overall, this suggests that killing of E. histolytica by activated macrophages depends on the production of reactive nitrogen intermediates which leads to critical iron loss and protozoan parasite death. PMID- 1614331 TI - Lipoteichoic acid and M protein: dual adhesins of group A streptococci. AB - The roles of lipoteichoic acid (LTA) and M protein in the adherence of group A streptococci to human cells were investigated. Both M+ and M- streptococci bound to pharyngeal and buccal epithelial cells in similar numbers. Streptococcal attachment was inhibited by LTA, but not by the pepsin-extracted, amino-terminal half of M protein (pep M), suggesting that M protein does not mediate attachment to these cells. However, a purified, recombinant, intact M protein did block attachment of streptococci to buccal cells. Using synthetic peptides, the inhibitory domain was localized to a region of intact M protein that is within or near the bacterial cell wall. Evidence is presented to suggest that on the surface of streptococci this region of the M protein is probably not accessible for interactions with host cell receptors and that M protein does not mediate attachment to buccal or pharyngeal cells. In contrast, approximately 10-times more M+ streptococci bound to Hep-2 cells than did M- streptococci and pep M protein blocked binding of streptococci to Hep-2 cells. The data suggest that at least two streptococcal adhesins, LTA and M protein, are involved in the adherence of streptococci to certain cells and that the relative contributions of these adhesins to the attachment process depends on the type of host cells used to study adherence. PMID- 1614332 TI - Plasmid-mediated serum resistance in Salmonella enterica. AB - The ability of Salmonella enterica to survive an incubation of 2 h in fresh, pooled guinea-pig serum was determined comparing strain sets of serovariants Dublin and Typhimurium, harbouring or lacking the virulence plasmid. All strains showed marked serum resistance, which was slightly decreased among cured strains of Typhimurium. However, when introduced into a rough Escherichia coli strain, all Typhimurium plasmids substantially increased the resistance of the host strain to guinea-pig serum, whereas the Dublin plasmid did not. The traT gene, previously shown to affect serum resistance, was identified on all Typhimurium plasmids, but not on the Dublin plasmid. Mutational inactivation of the traT gene on the Typhimurium plasmids eliminated the serum resistance mediated by the plasmids. PMID- 1614333 TI - Both adenylate cyclase and hemolytic activities are required by Bordetella pertussis to initiate infection. AB - Among virulence factors synthesized and secreted by Bordetella pertussis, pertussis toxin (PTX) and the bifunctional adenylate cyclase-hemolysin (AC-Hly) are able to invade mammalian cells and to impair intracellular functions. Moreover, both proteins are protective antigens in murine intracerebral and respiratory models. In order to study their in vivo properties, different B. pertussis mutants, deficient in AC-Hly expression or secretion, or producing modified AC-Hly devoid of either adenylate cyclase or hemolytic activities, were constructed and examined. The in vivo properties of the mutants were compared to PTX deficient strains, using the murine respiratory model. We show that lack of PTX as well as adenylate cyclase or hemolytic activities results in avirulence. Furthermore, we show that mutants lacking adenylate cyclase or hemolytic activities were unable to multiply as fast as the parental strains and PTX mutants during the first 5 days following infection. Thus, both adenylate cyclase and hemolytic activities are required by B. pertussis to initiate infection. PMID- 1614334 TI - Role of elastase as a virulence factor in experimental Pseudomonas aeruginosa infection in mice. AB - The role of elastase and alkaline protease in the pathogenesis of fatal infections caused by Pseudomonas aeruginosa was determined in mice treated with calcium chloride. Mortality increased significantly when solutions containing elastase were injected together with non-lethal inocula of strain PA 103, which does not produce proteolytic enzyme. In contrast, solutions containing alkaline protease did not increase mortality. In mice injected intramuscularly with strain PA 103 and calcium chloride, the organisms grew rapidly in the injected muscle but not in the liver. However, when elastase was injected together with strain PA 103 and calcium chloride, viable bacteria were also found in the liver. Moreover, the survival rate of mice challenged with elastase-producing strain 5 and calcium chloride was enhanced, and colonization of the liver prevented, by immunization with elastase toxoid. These results suggest that elastase contributes to the invasiveness of the organism. PMID- 1614335 TI - MSMS reimbursement roundup. PMID- 1614336 TI - Public health issues. AB - In a recent MSMS survey, MSMS members ranked public health as one the top five issues of major concern to Michigan physicians. Tobacco use, chronic illness, and HIV-infected health care workers comprise some of the major public health issues facing physicians and patients in Michigan. Following is a brief examination of each of these issues. Also included is a brief discussion of medical doctors as public health directors. Should all public health directors be medical doctors? This question is addressed in this cover story. PMID- 1614337 TI - Medicaid managed care comes of age. PMID- 1614338 TI - PRO update. Transition from the third to fourth scope of work. AB - The Health Care Financing Administration (HCFA) began implementation of the transition from the Third Peer Review Organization (PRO) Scope of Work to the Fourth PRO Scope of Work on October 1, 1991. PROs in 11 states are currently implementing newly-established medical review requirements under the "Scope of Work," the contract by which PROs are obligated to carry out their statutorily mandated duties of determining the medical necessity, appropriateness and quality of care delivered to Medicare beneficiaries. Michigan's PRO (MPRO) is scheduled to implement requirements outlined in the Fourth Scope of Work beginning April 1, 1992. This article discusses the American Medical Association's (AMA) relationship to the PRO program and the transition from the Third to the Fourth Scope of Work including the status of the Uniform Clinical Data Set. PMID- 1614340 TI - The need for a new paradigm for health. PMID- 1614339 TI - Gov. Engler deserves recognition, respect for his strong stand on liability reform. PMID- 1614341 TI - Health promotion and disease prevention. AB - Health promotion and disease prevention programmes improve the health status of populations, preserve freedom, and empower individuals. Yet, despite important advances in many countries, including a more health-conscious public, it would be beneficial in the United States and in other countries to have a comprehensive plan to make health promotion and disease prevention personal and societal priorities. I have called this climate a 'culture of character', a climate of individual responsibility to encourage healthy behaviour. I want to encourage the readers of Medical Education to participate in the formulation of plans to implement greater health promotion and disease prevention efforts. Such a climate of personal responsibility could be created if doctors, educators and policy makers agreed on some workable, positive goals and steps that would help meet realistic national goals over a defined period of time. If there were such agreement, then doctors could more clearly focus their own efforts with their patients, in concert with other health professionals, and with policy-makers who have the same goal--healthier people. PMID- 1614342 TI - Evaluation of teaching medical ethics by an assessment of moral reasoning. AB - This study assessed the hypothesis that the formal teaching of medical ethics promotes a significant increase in the growth and development of moral reasoning in medical students. Results indicated a statistically significant increase (P less than or equal to 0.0005) in the level of moral reasoning of students exposed to a medical ethics course compared to the control group that was not exposed to the medical ethics course. When the posttest scores were adjusted by subtracting the pretest scores, the differences were even more significant (P less than or equal to 0.0002). This study confirmed similar findings of another study using a different instrument of assessment. Brief discussion is given of the fundamental premise that the appropriate function of teaching medical ethics in our modern pluralistic society is to improve students' moral reasoning about value issues regardless of what their particular set of moral values happens to be. PMID- 1614343 TI - Teaching of medical ethics in Sri Lanka. AB - Medical ethics as taught by members of the Department of Forensic Medicine in three of five medical colleges in Sri Lanka is a 'rule ethic' ('normative ethic') based on 'traditional' or 'classical' ethics. Instruction includes the teaching of moral principles, illustrated with examples. Also included are aspects concerning the functions of the Sri Lanka Medical Council. The topic is evaluated in the essay, multiple choice question and oral components of the third MBBS (Part II) examination (end of fourth year). As presently taught the syllabus is thoroughly inadequate for dealing with modern (medical) ethical issues. The shortcomings and limitations in the present programme are pointed out and requisite improvements suggested. A case is made for an eclectic view of ethics, in which a 'situation ethic' would play a part. Finally, the training of a highly moral responsible medical professional is emphasized. PMID- 1614344 TI - From traditional to problem-based learning: a case report of complete curriculum reform. AB - The Sherbrooke School of Medicine, Quebec, has restructured its entire curriculum to make problem-based learning (PBL) the main instructional format. This complete reform is explained both in terms of process and content. The curriculum problems were clearly identified and overcome by a major structural shift-over following the stages of a strategic planning of change. Implementation over a period of 7 years is described according to a four-stage framework: need for change; selection of the PBL solution; planning for implementation; and the full-scale adoption of the PBL method. The programme is described in relation to the congruence of goals, learning and evaluation activities. Initial impact on student learning and evaluation, attracting better quality students, academic staff roles, and on financing the operation are discussed. Changing the undergraduate programme has become an institutional project directed by the Office of the Dean. PMID- 1614345 TI - Teaching medicine with cases: student and teacher opinion. AB - In a second-year family medicine course taught using simulated patients the students commented most favourably on the clinical relevance of the topics, the enthusiasm of teachers, and the opportunity to interview simulated patients with their fellow students, in contrast to their basic science courses, which did not give them patient contact. They felt most confident about skills acquired in relation to diseases with a limited number of key symptoms, signs and treatments (meningitis, otitis) and less confident about diseases with many symptoms and treatments (diabetes, trauma, arrhythmias). They made few comments about alternative cases which might have been selected. Their adverse comments were about the workload. During tutor meetings over 4 years, a key concern which emerged was to find cases with a level of complexity suitable to the students. The tutors emphasized these principles of case selection: the cases should be based on real life and include most of the signs and symptoms of the disease; contain one or at most two foci; have nodal decision-making points; emphasize clinical reasoning; reinforce prior knowledge; permit the transfer of knowledge to other cases; and permit the assessment of associated technical skills. PMID- 1614346 TI - Assessment of blood pressure measuring techniques. AB - The recommended techniques to measure blood pressure for assessment of hypertension are seldom followed in the ambulatory care setting. This study has found that interns and first-year family practice residents have significant deficits in their knowledge and use of the recommended techniques to measure blood pressure. The results suggest that inadequacies exist in the teaching of blood pressure measuring techniques in our medical schools, the consequences of which are misdiagnosis and improper treatment of high blood pressure. PMID- 1614347 TI - Practical medical education in general practice. AB - The Medical Faculty of the University of Limburg in Maastricht, The Netherlands pays special attention to extramural care. The extramural profile of the Medical Faculty also manifests itself in the curriculum. Since 1978, a 12-week clerkship in practical medical training in general practice (PMT-GP) has been offered to fifth-year students. The general aim is to acquaint students with general medical aspects as well as specific primary care aspects of health care. The programme started in the autumn of 1978 with 24 students and 24 GP teachers. At present more than 100 GP teachers, working in about 70 practices, train 120-130 students a year. The model of the PMT-GP system is characterized by six features: a ratio of one GP teacher to one student; autonomous examination by the student of at least 15 patients a week; daily follow-up discussion on the basis of patient records prepared by the student; opportunities for self-study by the student; one tutorial day a week at the Medical Faculty; intensive contacts between the Faculty and GP teachers. Key activities of the PMT-GP include autonomous contacts with patients, written records and daily follow-up discussions with the GP teacher. PMID- 1614348 TI - Measuring the quality of junior hospital doctors in general medicine. AB - During the course of a larger study aimed at relating staffing levels of junior doctors in general medicine to the safety of the care provided, it became clear that consultant doctors considered the quality of their junior staff as being at least as important as the quantity. This paper describes several attempts to develop a feasible and valid method of measuring the quality of senior house officers (SHOs) and registrars using routinely available data. Having rejected three methods and had difficulties with three other methods, a modified Delphi survey was used to explore the extent to which consultants agreed on the key attributes of a high quality SHO or registrar. Sixty-seven (60%) of all consultants in the South-West Thames and Trent regions responded to two rounds of questionnaires which revealed communication skills as being consistently the most significant factor. This was confirmed in a second, anonymous survey of 198 (78%) SHO and registrar posts in the North-West Thames region. It also became clear that consultants viewed the quality of their own SHOs and registrars as generally high. This being so it is argued that the requirement to adjust for quality, when comparing SHO and registrar levels between hospitals, is of minor importance. These results also suggest that the explicit teaching of communication skills should have a high priority in undergraduate and postgraduate education. PMID- 1614349 TI - Allocation of junior hospital doctors to pre-registration posts: does Britain need a national matching scheme? AB - The attitudes of British postgraduate deans and senior medical students to the introduction of a national pre-registration house officer allocation scheme were investigated by postal questionnaire. Several postgraduate deans expressed interest, but most were not in favour of the proposal. Students held similar views. The advantages and disadvantages of a national scheme are discussed. PMID- 1614350 TI - Performance evaluation of graduates from a community-based curriculum: the housemanship period at Gezira. AB - The housemanship performance of the first two classes of the University of Gezira Medical School was assessed on 107 occasions by using a questionnaire administered to the senior doctors (consultants) in the units in which they worked and the data, which covered 32% of all housemanship rotations taken by these graduates, were analysed. On a 5-point scale (poor to excellent) the rating of performance for 26 questions was average and above (S = 3: + S = 4: + S = 5) in 95% of instances. The good and excellent rating (S = 4 + S = 5) for the same questions was about 80%. The grand mean for rating of questions in the cognitive, psychomotor and attitudes domain was 4.1, 3.9 and 4.2 out of 5 respectively. The graduates were found to be better off (45%), comparable to (50%) and less than (5%) when compared to other graduates who worked with the same consultants in the past. Results of three general questions inquiring about graduates' practice safety, overall standing and consultants' preference for Gezira graduates had a 95% positive rating. It is concluded that these results provide significant positive answers for some basic questions concerning credibility which are often raised about Gezira and similar schools with innovative medical curricula. PMID- 1614351 TI - Improving presentation skills of family medicine residents: a randomized controlled study. AB - A randomized controlled time series design was used to evaluate the influence of an educational intervention designed to improve the presentation skills of family medicine residents. Each resident gave three presentations, with the educational intervention occurring between the first and second presentations in the experimental group, and between the second and third presentations in the control group. The presentations were evaluated using a standardized format. The experimental group, in contrast to the control group, showed significant improvement in scores for all major criteria after receiving the educational intervention between presentations 1 and 2. This improvement continued with repetition between presentations 2 and 3. After receiving the educational intervention between presentations 2 and 3, the control group also demonstrated significant improvement in several key areas. We conclude that an educational intervention can improve the presentation skills of family medicine residents. Education coupled with repeated opportunities for presentation will produce a greater improvement in resident performance than repeated presentations alone. PMID- 1614352 TI - Continuing medical education and the education allowance: variation in credits obtained by general practitioners. AB - The educational credits obtained by general practitioners for the postgraduate education allowance were examined. With over 3 months of the qualifying period remaining, 68.4% had reached the requirement. The educational day attainments show almost a normal distribution, with 4.2% of doctors completing more than double the requirement. PMID- 1614353 TI - Medical education in Thailand. AB - In order to make training more relevant to community needs, medical educators throughout Thailand have been attempting to address issues concerning the training of their undergraduates. Support for a reorientation of medical education and acceptance of the frame-work put forward by the World Health Organization are evident in national health plans and in national medical education conferences. This paper outlines some of the basic problems faced by health policy makers in Thailand and presents a brief chronology of recent events in the history of medical education in Thailand. PMID- 1614354 TI - Alzheimer's disease and metal-containing glia. AB - Considerable evidence suggests that in Alzheimer's disease, olfactory bulb damage may be a primary factor, causing degeneration and neurofibrillary tangles primarily in neurons connected with this brain area. Also, deposits of amyloid may involve an improper regulation of the cleavage of a precursor protein by glia. Finally, toxic effects of aluminium may be an etiological factor. This review proposes that all these seemingly unrelated aspects of Alzheimer's disease could be related to a disturbed function of metal-containing glia. Such a disturbance, initiated by or aggravating toxic effects of aluminum, may underlie initial damage in the olfactory bulb and/or other brain areas with a weakened blood-brain barrier and may be responsible for amyloid deposition. PMID- 1614355 TI - Eliminating human immunodeficiency virus (HIV) from infected individuals and cells: is it possible? AB - The literature from 1984 to 1991 has been searched for reports of patients who have eliminated human immunodeficiency virus (HIV) from their system. While such reports are scarce, it appears that a small number of HIV-positive patients have reverted to a negative state either spontaneously or following radical immunosuppressive regimens for neoplastic disease. Although no carefully planned animal experiments or clinical trials have been reported, it would appear that bone marrow ablation and replacement may eliminate HIV from healthy, asymptomatic HIV-positive individuals. Although much of the clinical experience to date suggests that radical immunosuppression is not indicated in advanced AIDS patients in whom the virus has likely spread beyond the immune system, such cases do not represent evidence that immunosuppression is not indicated in healthy, HIV positive individuals. PMID- 1614356 TI - Early impressions concerning actinomycetal infections that may play a role in the pathogenesis of eosinophilia-myalgia syndrome (EMS) and other 'new illnesses'. AB - Actinomycetal infections by Actinomyces, Nocardia, and Streptomyces appear to be increasing in incidence. Clinical and laboratory data from twelve patients believed to have subclinical actinomycete-streptomycete infections (ASI)* are presented. It is proposed that the recent epidemic of eosinophilia-myalgia syndrome (EMS) may have been caused by pre-existing host ASI that generated toxic agents when individuals ingested supplemental L-tryptophan (LT). LT is the substrate used by streptomycetes to synthesize actinomycins, extremely cytotoxic metabolites that could have accounted for symptoms seen in EMS. Actinomycins inhibit CoA activity and interfere with the synthesis and utilization of amino acids. LT also provides streptomycetes with additional NAD, a substance of great importance to their DNA synthesis and metabolic activity. With increased activity, streptomycin, chloramphenicol, adriamycin or any one of the many secondary metabolites (antibiotics) produced by Streptomyces could be endogenously generated in greater quantities. The clinical result would be increased host toxicity. A contaminant that has been isolated from case associated lots of LT may have simply provided additional tryptophan for an ASI. It is also possible that a nucleotide or similar substance in the case associated LT products caused increased activation of tryptophan-2,3-dioxygenase, the rate limiting enzyme required for the production of NAD and/or actinomycin. Potential reasons for ASI, atypical forms of actinomycete-streptomycete micro-organisms, and the possibility of involvement in other diseases are discussed. PMID- 1614357 TI - Degenerative and inflammatory diseases may result from defects in antimineralization mechanisms afforded by glycosaminolglycans. AB - Many human cellular and tissue compartments are supersaturated with respect to calcium oxyanion salts. In order to prevent the formation of injurious crystals efficient anti-crystallization protective mechanisms must be necessary. We suggest that depletion of such systems, particularly in ageing organisms and under conditions of oxidative stress, plays an important role in degenerative and inflammatory diseases, including cancer. PMID- 1614358 TI - The puzzle of Alzheimer's disease (AD). AB - A compromised defensive system of brain cells against aluminium, together with local defects in glucose metabolism, causes AD. Lack of citrate is a driving force and free cis-aconitate or glutamate are potential carriers, which enable the exotoxin to cross lipid membranes. Only a few aluminium ions replace magnesium in key positions. They block the reversibility of phosphorylation reactions, which are important for short term memory: sensitization of the insulin receptor and protein phosphorylations. Due to disturbed phosphorylation of the cytoskeleton, protein synthesis runs out of balance. Efforts to restore the disturbed reactions result in AD specific deposits. Aluminium ions are the common cause for the induction of AD pathogenesis in patients with genetic defects, with mechanical brain lesions or with minor infarcts, as well as with changes in the relation between numbers of neurons and neuron nursing glia cells due to age. PMID- 1614359 TI - Magnetic influences on fetus and infant as reason for sudden infant death syndrome: a new testable hypothesis. AB - The hypothesis is based upon: a) My observed clustering of Sudden Infant Death Syndrome (SIDS) cases at places with abnormal geomagnetic fields (GMF) and/or electromagnetic fields (EMF); b) recorded GMF with pulsations matching the breathing frequencies of infants; c) the reported immature development of increased dendritic spine density in the brain stem of SIDS cases and; d) the increased dendrite arborization in the brains of rats exposed to magnetic fields (MF). The hypothesis consists of two parts: 1. A disturbed GMF in the residence or surroundings of a pregnant woman may interrupt the normal development of the central organ which controls respiration (brain stem) of the fetus. This is termed the 'Selection Factor'. 2. If such an infant with a functional disturbance of the control organ is then exposed to a GMF or EMF with pulsations similar to his own breathing frequency, but inverted in phase, value, form etc then the vital nerve impulses from the respiration control organ to the breathing organs may be disturbed or blocked with fatal effect. This is termed the 'Trigger Factor'. The elements of the 'Selection Factor' and the 'Trigger Factor' together produce SIDS. A program to test such a supposed 'Trigger Factor' is included. PMID- 1614360 TI - A new role for an old hormone: is gastrin a cofactor for dietary metal ion uptake? AB - It is proposed that gastrin promotes the uptake of divalent and trivalent metal ions from the gastrointestinal lumen by catalyzing the binding of metal ions to luminal albumin and transferrin respectively. The following observations are consistent with this hypothesis: 1. Gastrin binds both divalent and trivalent metal ions. 2. Gastrin binds to both albumin and apotransferrin. 3. Binding of gastrin to albumin is enhanced by divalent metal ions. 4. Gastrin, albumin and transferrin are all present in gastric juice. 5. Surgical removal of the gastric mucosa results in iron deficiency. PMID- 1614361 TI - Deficiency of copper can cause neuronal degeneration. AB - The aim of this article is to emphasize the important role that copper plays in the function of nerve cells. We are reporting preliminary data which suggest that the swelling of axons which we produce in rats by iminodipropionitrile, IDPN, is due to its chelating action on copper, and how conversely supplementation with copper abolishes both symptoms and lesions. The copper values we obtained by atomic absorption spectrophotometry of the spinal cord and brain from the animals fully support this contention. In comparing these results with the diseases that are known to be due to copper deficiency, namely Menkes disease in man, swayback in lambs and several neurological mutant mice, we find not only similar axonal swellings, but also amelioration of symptoms and lesions by early administration of copper. Considering the main forms in which copper is present, we discuss the cuproproteins, i.e. ceruloplasmin and metallothionein, and their role in transport and delivery of copper to various organs. Further, the many cuproenzymes i.e. superoxide dismutase, tryptophan-2,3-dioxygenase, lysine oxidase, cytochrome oxidase, monoamine oxidases, tyrosinase, dopamine-beta hydroxylase and d-amino levulinate dehydratase are noted for their roles in the nervous system. Finally, we suggest that neuronal copper deficiency should be more fully investigated as a possible etiological factor in the more common neurodegenerative diseases, such as Alzheimer's disease and amyotrophic lateral sclerosis, ALS. PMID- 1614362 TI - Prevention of gallstone migration from the gallbladder into the cystic duct. AB - Biliary colic is caused by an increased pressure within the gallbladder lumen due to gallbladder contraction against an impacted stone in the cystic duct. It should be possible to prevent the passage of stones into the cystic duct by avoiding those body positions (mostly the supine position) in which the neck of the gallbladder is located in the downward position. PMID- 1614363 TI - Concept of the development of the mammalian cerebellum based on physical rotation forces. AB - In pre-mammalian forms the cerebellum (rhombencephalon) has no rhombic lip and it develops in the median region between the two auricles above the front end of the fourth ventricle. In mammals, cells in the superior rhombic lip and dorsal part of the dorsal lamina of the metencephalon are said to proliferate to form two rounded swellings, the rudiments of the cerebellum. This assumption does not explain many peculiarities of the mammalian cerebellum, 11 of which have been described. The crux of the present hypothesis is that the mammalian cerebellar hemispheres and vermis develop from the median cerebellar element seen in the pre mammalian forms and that the vermis does not develop as a confluence of the two hemispheric tissues. PMID- 1614364 TI - The impact origin of genetic material. AB - It is proposed that high velocity asteroidal impacts with the Earth created polymeric nucleotide sequences out of monomeric nucleotides via direct compressive forces. The developed model describes the simultaneous formation of histone-equivalent proteins and RNA/DNA-equivalent template structures as a natural and expected consequence of bolide impactions with organic material accumulating on the crustal surface of the Earth approximately 3.8-3.5 billion years ago. It is shown that literally billions of different gene-equivalent nucleotide sequences, each one having a set of surface-complementary histone equivalent proteins, might be created in such a manner. It is hypothesized that it is this process that gave rise to the chemical substrate upon which Darwinian selective forces have acted ever since. PMID- 1614365 TI - [Renin inhibitors for lowering blood pressure]. PMID- 1614366 TI - [Preventive tuberculosis vaccination--pro and contra]. PMID- 1614367 TI - Ticlopidine for prevention of stroke. PMID- 1614368 TI - [The disease or the patient--priorities in education and internal medicine general practice]. PMID- 1614369 TI - [Local excision of rectal tumors. Indications, preoperative diagnosis, surgical technique and results]. AB - Between January 1986 and October 1991 255 patients with rectal tumors were treated by local excision. In 239 patients local excision was performed by transanal endoscopic microsurgery, 16 tumors were removed with the retractor developed by Parks. Operative mortality was 1% in 189 local removed adenomas, complications were observed in two patients (2.1%), local recurrences in seven patients (3.7%). 66 rectal carcinomas were treated by local excision (operative mortality 1%, complication rate 3%). In one of 28 local excised "low risk" T1 carcinomas a recurrence was observed. Five of eleven local treated patients with "high risk" tumors developed a recurrence. Endosonography was of utmost importance in preoperative staging of rectal tumors. Between June 1987 and October 1991 204 patients with rectal tumors (92 sessile adenomas, 30 T1 carcinomas and 82 advanced carcinomas) were examined preoperatively by endosonography. The diagnosis of an adenoma or a T1-carcinoma was made with a sensitivity of 0.9, although no differentiation was possible between adenomas and T1-carcinomas. Results of digital examination were comparable to endosonography, under condition that digital examination was complete. Insufficient information was obtained from the endosonographic detection of lymph-node metastatic spread. PMID- 1614370 TI - [Chronic diarrhea, steatorrhea and protein deficiency in a 27-year-old patient]. PMID- 1614371 TI - [Intensive care of patients with obstructive lung diseases]. PMID- 1614372 TI - [Pathogenesis and therapy of gallstone disease]. PMID- 1614373 TI - [Principles and concepts of immunosuppressive therapy of glomerulonephritis]. PMID- 1614374 TI - [The best possible preparation for coloscopy]. PMID- 1614375 TI - [Communicating medicine--luxury or necessity?]. PMID- 1614377 TI - [Inflammatory muscle diseases. International symposium "Inflammatory myopathies", Munich 26 September 1991]. PMID- 1614376 TI - [Use of amrinone in terminal dialysis-dependent renal failure]. PMID- 1614378 TI - [Haemophilus endocarditis]. PMID- 1614379 TI - The changing profile of the elderly: effects on future long-term care needs and financing. AB - Simulation techniques are used to analyze the changing profile of the elderly from 1990 to 2030. The results show that the future demand for long-term care services is likely to be greater than many realize. Increases in the number of elderly who are 85 years of age and older, who have health limitations, or who live alone are likely to outpace the general increase in the elderly population. Although there will be a very large group of elderly at risk, their economic status will be better than that of today's elderly population. The percentage of elderly who can afford insurance premiums for broad long-term care coverage will increase in the future, but most older Americans probably will not be able to afford insurance. Although policies that reduce the cost and encourage the purchase of long-term care insurance could help to expand coverage, a large long term care financing gap is likely to remain for the future elderly population. PMID- 1614380 TI - Public and private responsibility for financing nursing-home care: the effect of Medicaid asset spend-down. AB - Data from a nationally representative sample of nursing-home residents at the beginning of 1987 are used to assess the interaction of Medicaid asset spend down, the distribution of nursing-home days by payment source, and the effect of proposed changes in public financing of nursing-home care. Three out of five nursing-home residents were covered by Medicaid in January 1987; nearly all of the remainder were private-pay. Most Medicaid recipients were covered by Medicaid when they entered the care facility at the start of an episode, but 18 percent had spent down and were originally admitted as private-pay. A universal nursing home benefit that insured the first six months of each nursing-home episode would cover 16 percent of the people in nursing homes on a given day, disproportionately those who are private-pay. A universal benefit with a 24-month waiting period would cover 56 percent of nursing-home residents on a given day, and would tend to favor those financed by Medicaid. PMID- 1614381 TI - Competition for altruism: bone and organ procurement in the United States. AB - The number of "units" of human bone used during surgical procedures has grown to almost a quarter of a million. Medical demand for such bone is expanding rapidly and the nation's bone-banking system is struggling to grow apace. Unfortunately, because of this growth, bone banks must compete with organ banks for access both to hospitals and to potential donors. This conflict can, and may already be, negatively affecting the supply of transplantable tissues and organs. The nature of this conflict is affected by current law and public policy, but those effects are little understood and perhaps not intended. PMID- 1614382 TI - Federal budgetary costs of blindness. AB - Federal expenditures for blindness-related disability among Americans are examined. The government, rather than the private sector, frequently bears the economic consequences of visual disability through entitlement and public assistance programs. Findings suggest an average $11,896 federal cost of a person year of blindness for a working-aged American, which includes income assistance programs (SSDI/SSI), health insurance programs (Medicare/Medicaid), and tax losses resulting from reduced potential earnings. Almost 97 percent of the aggregate annual federal costs of blindness in 1990, which totaled approximately $4 billion, is accounted for by working-aged adults, who represent less than one third of the total blind population. Approximately 25 percent of all blindness is attributed to preventable causes. PMID- 1614383 TI - Health policy and the distribution of lifetime income. AB - A number of health policies have implications for, and in turn can be influenced by, the distribution of income. However, current discussions define the distribution in current, not lifetime, income. This study describes a method of estimating gender and race differences in the distribution of lifetime incomes that account for mortality differences. When cohort lifetime incomes of living and deceased persons are compared, black men are found to be much worse off, whereas white women are found to be better off than existing estimates using annual income suggest. The mortality and lifetime income advantage of white women, however, is offset if, as some argue, white women have higher morbidity rates than white men of the same age. The authors use the concept of lifetime income to draw implications for health policy debates on cigarette and beer taxes, occupational safety and health, Medicaid versus Medicare spending, educational health promotion programs, and general investments in education. PMID- 1614384 TI - The case of the disappearing generalist: does it need to be solved? AB - The proportion of generalist physicians in the United States has declined steadily over 50 years, bringing it to the lowest percentage of trained primary care physicians of any developed country; the trend toward subspecialization is accelerating. Many analysts believe this imbalance between generalists and subspecialists to be a major cause of America's high health care costs, heavy dependence on biotechnology, and consumer dissatisfaction. Others argue that sub specialists can provide excellent primary care services, and the decrease in the number of generalists is not a problem. Three contrasting views on the implications of this trend state that today's generalists are an important and scarce resource that must be bolstered; that subspecialists can replace generalists as providers of primary care; and that the free market will determine the best manpower mix. A final view, on the marketplace option, posits that generalism will not recover until it creates a vital, and unique, role in handling the primary care challenges of the twenty-first century. These competing viewpoints are used to clarify assumptions underlying our major policy options in the arena of health manpower. PMID- 1614385 TI - Missing: a national medical manpower policy. PMID- 1614386 TI - Accessibility of cigarettes to youths aged 12-17 years--United States, 1989. AB - Rates of tobacco-related diseases are higher for persons who initiate smoking at younger ages than for those who begin at older ages (1). Restricted access to tobacco products may delay or prevent the decision by adolescents to initiate tobacco use (1,2). This report summarizes findings from the Teenage Attitudes and Practices Survey (TAPS) regarding minors' access to cigarettes during 1989.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614387 TI - Scalping incidents involving hay balers--New York. AB - In August 1991, the Agricultural Health Nurse Program (AHNP) of New York received a report of a woman who was scalped (i.e., traumatic avulsing of the scalp) when her hair became entangled in a hay baler. Subsequent investigations by the AHNP identified three similar incidents. One was identified through a rehabilitation service and one by a machinery dealer; one of these women identified the third person. In all four cases, the injuries resulted from entanglements with rotating secondary drivelines, shielded from above by three-sided guards, on hay-baling equipment. This report summarizes the four incidents and discusses strategies for prevention of similar incidents related to operation of farm machinery. PMID- 1614388 TI - Spina bifida incidence at birth--United States, 1983-1990. AB - Spina bifida, a birth defect of the spinal column that can cause varying degrees of paralysis, is a major contributor to serious developmental disabilities in the United States. To determine the incidence and descriptive epidemiology of spina bifida, CDC analyzed reports from 16 states with population-based birth defects surveillance systems (Table 1). This report summarizes findings from this analysis for 1983-1990.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614389 TI - Recommendations regarding penicillin-resistant pneumococcal disease--Spain. PMID- 1614390 TI - [A study on a postoperative change of beta-2-microglobulin in surgical patients]. AB - Various renal tubular functions were monitored perioperatively in 42 surgical patients and the validity of beta-2-microglobulin (BMG) was evaluated. NAG index (urine NAG titer/urine creatinine), the absolute value of free water clearance and fractional excretion of sodium were worse at 3 to 5 hours after the beginning of operation, indicating the latent renal tubular damage took place during operation. On the other hand, fractional excretion of BMG (FE-BMG; BMG clearance/creatinine clearance) slowly elevated after operation and reached a peak on the 2nd postoperative day. The postoperative change of C-reactive protein (CRP), was similar with that of FE-BMG, showing a significant correlation (r = 0.716, p less than 0.001). The close relationship between CRP and FE BMG was confirmed in 26 patients with or without abnormal liver function who underwent abdominal operation. The peak value of FE BMG was significantly (p less than 0.01) lower in 5 patients with ICG 15' greater than 25% than in 21 patients with ICG 15' less than 20%. Similarly, the peak value of CRP tended to be lower in the former group. In conclusion, FE BMG can not be employed as an indicator of renal tubular function during postoperative period. It reacts as an acute phase reactant like CRP and is probably produced in the liver. PMID- 1614391 TI - [Experimental study of lymph node metastasis in thoracic esophageal carcinoma- regarding lymph node metastasis and changes in lymphatic flow by ultrafine charcoal in rabbit esophageal carcinoma model]. AB - Esophageal carcinoma models were created by transplanting VX2 cells to rabbit esophagus endoscopically. By injecting finely divided activated charcoal into normal rabbit esophagus and tumor sites of esophageal carcinoma model, lymph flow was observed directly. Existence of lymph node metastasis was studied in detailed pathology. In 30 rabbits with upper esophageal carcinoma, lymph node metastasis was seen in 77%. Metastasis to bilateral intrathoracic paratracheal lymph node was seen in 50%, and also concentration of lymphatic flows from tumor site was seen. However, there were no metastasis and no lymph flow to abdominal lymph nodes. While, metastasis to cervical lymph nodes showed around 13%. Esophageal lymphatic flows were also seen reaching the cervical area along the esophagus. In 40 models with mid lower esophageal carcinoma, lymph node metastasis were seen in 88%. Metastasis to right and left thoracic paratracheal lymph nodes was 75% and 53%, respectively, and 25% of metastasis went to cardia lymph nodes. The lymph flows were going up and down around these lymph nodes, and reaching to lymph nodes at upper highest mediastinum or left gastric artery. The metastatic rate to the cervical lymph nodes was about 5%. There were no significant differences in lymphatic metastasis between right and left mediastinum. These findings suggest the necessity of radical dissection for both sides of the mediastinum. PMID- 1614392 TI - [Combined resection of respiratory tract for thoracic esophageal carcinoma]. AB - Thirty seven patients with thoracic esophageal carcinoma underwent esophagectomy combined with resection of respiratory tract. In 5 patients who received resection with the trachea or bronchus, 1 patient survived more than two years. His status of lymph node metastasis was n2 positive, and surgical margin was free of cancer. These findings show that negative surgical margin and certain lymph adenectomy are required to obtain good prognosis. A half of 32 patients who received combined resection of the lung had no invasion into the lung tissue pathologically. Five-year survival rate of 32 patients was 22.9%. We concluded that combined resection of the lung was safe procedure and showed satisfactory outcome. PMID- 1614393 TI - [Enhancement of anti-tumor effect of adriamycin by verapamil in a intrahepatic arterial infusion in the rats]. AB - In a intrahepatic arterial infusion, the enhancement of cytotoxicity of adriamycin (ADR) by verapamil (VER), a calcium antagonist was investigated in male Wistar rat with liver tumor of Walker 256 carcinosarcoma. The accumulation of ADR in tumor tissue at 2 hrs after a bolus intrahepatic arterial injection of ADR with VER (4 mg/kg) was 1.9-fold more than without VER. But VER did not enhance it in normal liver tissue and heart tissue. In the continuous intrahepatic arterial infusion therapy (cia) of ADR and VER (1.5 mg/kg/day) for 6 days, tumor weight and the accumulation of ADR in tumor tissue, normal liver tissue and heart tissue were assessed. Tumor weight of ADR-cia+VER-cia group was significantly less than ADR-cia group (p less than 0.05). And the accumulation of ADR in tumor tissue of ADR-cia+VER-cia group was significantly higher than ADR cia group (p less than 0.05). But VER did not enhance it in normal tissue. The administration of VER in a intrahepatic arterial infusion is shown to be able to enhance the cytotoxicity of ADR in tumor tissue but not to enhance in normal tissue. The continuous intrahepatic arterial infusion of VER enhanced cytotoxicity of ADR at clinical dose and it suggests the clinical applicability of VER in cancer chemotherapy. PMID- 1614394 TI - [Biological effect of estrogen metabolites in human breast cancer]. AB - In order to investigate the estrogen metabolism in human breast cancer, the estradiol 2- and 16 alpha-hydroxylase (2-, 16 alpha-OHase) activities were determined in the microsomal fractions of human breast tissues by using reverse phase HPLC. The effects of estrogen metabolites on the cell proliferation were also examined by employing two human breast cancer cell lines. The 2-OHase activity was detected in most cancerous and noncancerous tissues, but the value in cancerous tissues was significantly lower than that in noncancerous tissues (p less than 0.05). Patients without lymph node metastases showed relatively higher activity than those with metastases (0.05 less than p less than 0.1). The 16 alpha-OHase activity was, however, found in only 23% of cancerous tissues. Among those, the activity was present in 52% of ER positive cancerous tissues, but almost absent in ER negative ones. The growth ER positive cell line, MCF-7, was suppressed with 2-hydroxyestrone and stimulated with 16 alpha-hydroxyestrone. The cell proliferation stimulated with 16 alpha-hydroxyestrone was not inhibited by the addition of tamoxifen, a strong antagonist of estradiol. Two metabolites had no effect on the growth of ER negative cell line, MDA-MB-231. These results suggest that estrogen metabolites influence the proliferation of human breast cancer cells as the endogenous regulatory factors and should be considered for the future endocrine therapy. PMID- 1614395 TI - [Abdominal complications of the pedicled omental flap in chest surgery]. AB - The incidence of abdominal complications and the gastrointestinal function after omental pedicle wrapping (Group I: n = 13) were compared with those after right pneumonectomy (Group II: n = 9) and cholecystectomy (Group III: n = 22). Indications of the omentopexy were as follows: 1) prophylaxis for the bronchial complication after chest surgery (4 cases), 2) treatment of thoracic empyema (2 cases) and 3) postoperative bronchopleural fistula (7 cases). Poor intestinal movement necessitating fast after surgery persisted significantly longer in Group I than in Group II (p less than 0.05), but no significant difference was observed between Group I and Group III. Abdominal complications were observed frequently in Group I when oral feeding was initiated; abdominal distension in 7 of 13 cases (54%), epigastric discomfort in 3 (23%) and dehiscence of the abdominal wound in 4 (31%). Abdominal wound dehiscences were most frequently encountered after surgical treatment with the omentopexy for empyema thoracic (2/2, 100%) and for bronchopleural fistula (2/7, 28%). Upper GI examination was performed in seven cases, four of which (57%) showed the deformity of antral region of the stomach. Since this finding was not always accompanied with the symptom of gastric retention, it was likely that gastric retention following the omentopexy was caused by dissection of right gastroepiploic nerves rather than the anatomical deformity of the stomach. PMID- 1614396 TI - [Morphological and functional studies on implanted arterial graft]. AB - Early morphological and functional changes in arterial graft were studied. Autologous free graft of dog femoral artery or vein was implanted in the arterial system and the changes of endothelial cell by scanning electron microscope and prostacyclin levels were observed. In arterial graft, endothelial cell detachment after the implantation was rarely observed except the site with mechanical damage around the anastomosis. The site of cell detachment regenerated by 21 days after the implantation. The prostacyclin level was 2.5 pg/mg in venous graft or 35.9 pg/mg in arterial graft. The level in venous graft decreased after the implantation and it increased according to the cell regeneration, while the level was stable in arterial graft. The prostacyclin level of internal thoracic artery or gastroepiploic artery in clinical use was 54.5 pg/mg or 50.1 pg/mg, respectively. However the level in saphenous vein (SV) was 17.3 pg/mg and there were significant differences between the levels of arterial grafts and one of SV. Conclusively the arterial graft was superior to venous graft in early morphological and functional changes after the implantation and the superiority in early period after graft implantation may be one of the factor to contribute good graft patency in long term period. PMID- 1614397 TI - [Primary malignant lymphoma of the esophagus--a case report]. AB - We report a rare case of primary malignant lymphoma of the esophagus without extraesophageal involvement. A 69-year-old woman was referred to our hospital because of dysphagia. Esophagogram revealed an irregularly marginal ulceration with stenosis at the abdominal esophagus. Endoscopic study showed an ulcerative lesion at the level of 30 cm from the incisor teeth. Esophagocardiectomy was performed. Resected specimen showed a shallow depressed ulceration, 6.5 x 6.0 cm in size, at the lower esophagus. Microscopic examination revealed malignant lymphoma of diffuse, large cell type. No evidence of involvement was found in the dissected lymph nodes and the bone marrow biopsy specimens. She has been well for 4 years and 6 months postoperatively. PMID- 1614398 TI - [A case of intrahepatic cholesterol stone complicated with atrophy of the anterior superior ventral and anterior superior lateral subsegments (S8ab) of the liver]. AB - A 61-year-old male patient with intrahepatic cholesterol stone is reported. Stones were detected in the anterior superior lateral subsegment (S8ab) of the right lobe with bile duct stenosis, the lateral anterior segment (S3) of the left lobe, and the left caudate lobe (S11). Partial hepatectomy including S8ab, S3 and S11 was performed to remove all stones. Atrophy of S8ab was diagnosed by CT, and PTP clarified the patency of the subsegmental portal vein (P8ab). This is a rare case with cholesterol intrahepatic stone with regional bile duct stenosis and subsegmental atrophy of S8ab of the liver. PMID- 1614399 TI - [Local recurrence of differentiated thyroid carcinoma effectively treated by local injection of OK-432]. AB - Local recurrence of differentiated thyroid carcinoma in a 67-year-old woman was treated by topical injection of OK-432 every 2-4 weeks. Recurrent tumors turned into small scar-like tissues after 9 months of OK-432 administration. The bleeding from the tumor was well controlled. Secondary recurrent tumors were also effectively treated in the same manner. About 2 years have passed since the start of the treatment and the local recurrence is well controlled. We conclude that topical injection of OK-432 might be a good modality of treatment for the local recurrence of thyroid carcinoma. PMID- 1614400 TI - [A case of pheochromocytoma in pregnancy]. AB - A 29-year-old woman was referred to our hospital at the 34th week of her first pregnancy with a diagnosis of severe pregnancy-induced hypertension. A diagnosis of pheochromocytoma was made by elevated values of serum and urinary noradrenaline. Ultrasonography and computed tomography revealed a left adrenal tumor. Caesarean section combined with removal of the tumor at the 36th week of gestation was performed with a satisfactory result obtaining a healthy mother and an infant. Current management of patients with a pheochromocytoma during pregnancy is discussed. PMID- 1614401 TI - [Modulation by recombinant alpha-2a-interfer on the activity and site of action of 5-fluorouracil on xenografted human colon cancer in nude mice: preliminary report]. PMID- 1614402 TI - [Pancreatic mitochondrial fragility and impaired pancreatic energy metabolism induced by cyclosporin A in rats; preliminary report]. PMID- 1614403 TI - [A metastatic model of human gastric cancers using orthotopic tissue implantation in nude mice: preliminary report]. PMID- 1614404 TI - [The effect of duodenal reflux on esophageal carcinogenesis in rats: preliminary report]. PMID- 1614405 TI - [Adsorption of natural antibodies with acetone-treated tissue powder: preliminary report]. PMID- 1614406 TI - Increased glucocorticoid receptor gene promoter activity after antidepressant treatment. AB - We have tested the hypothesis that antidepressants affect the expression of the glucocorticoid receptor gene, by looking at glucocorticoid receptor gene promoter activity, glucocorticoid receptor mRNA levels, and glucocorticoid-binding activity after treatment of different cell lines with desipramine. Treatment of LTK- cells or Neuro 2A cells with desipramine produced a 50-200% increase in chloramphenicol acetyltransferase activity transcribed from a 2.7-kilobase glucocorticoid receptor gene promoter region. In cell lines derived from both neuronal and non-neuronal sources, glucocorticoid receptor mRNA concentration doubled after desipramine treatment, and this was associated with a 2-fold higher functional glucocorticoid binding capacity and increased glucocorticoid sensitivity, as measured with the reporter plasmid pMMTVCAT. Antidepressant induced increases in glucocorticoid receptor gene promoter activity, glucocorticoid receptor mRNA levels, and functional glucocorticoid binding activity suggest a novel mechanism of action for these drugs on the hypothalamic pituitary-adrenal axis. PMID- 1614407 TI - Overcoming of vinblastine resistance by isoquinolinesulfonamide compounds in adriamycin-resistant leukemia cells. AB - We investigated the effects of seven isoquinoline derivatives in overcoming resistance to vinblastine in Adriamycin-resistant mouse leukemia P388/ADR cells and human myelogeneous leukemia K562/ADR cells. N-(2-Methylpiperazyl)-5 isoquinoline-sulfonamide (H-7), N-[2-(methylamino)ethyl]-5 isoquinolinesulfonamide (H-8), and N-(2-aminoethyl)-5-isoquinolinesulfonamide (H 9) did not reverse resistance to vinblastine in these resistant cells. N-[2-[N-[3 (4-Chlorophenyl)-2-propenyl]amino]ethyl]-5- isoquinolinesulfonamide (H-86) and N [2-[N-[3-(4-chlorophenyl)-1-methyl-2-propenyl]- amino]ethyl]-5 isoquinolinesulfonamide (H-87) caused significant accumulation of intracellular vinblastine and marked reversal of the resistance to vinblastine in both resistant cell lines. Addition of a formyl group at the terminal amino group of H 86 (H-85) or addition of an aminoethyl group to the nitrogen atom at the sulfonamide group of H-86 (W-66) reduced those activities. The activity on vinblastine accumulation seems to correlated with the hydrophobicity of the compounds. The compounds that effectively reversed resistance to vinblastine inhibited [3H]vinblastine efflux and photoaffinity labeling of P-glycoprotein with a photosensitive analogue of vinblastine, N-(p-azido-(3-[125I]iodo)-salicyl) N'-beta-aminoethylvindesine. Although these isoquinoline derivatives inhibited protein kinase A and protein kinase C with various potencies, these inhibitory activities did not correlate with the reversal of drug resistance. These results indicate that hydrophobic isoquinoline derivatives reverse multidrug resistance due to the suppression of drug binding to P-glycoprotein, without involvement of their activities on protein kinase A and protein kinase C. PMID- 1614408 TI - Distribution of cytochrome P450 1A1 and NADPH-cytochrome P450 reductase in lungs of rabbits treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin: ultrastructural immunolocalization and in situ hybridization. AB - Induction of cytochrome P450 1A1 (P450 1A1) in a variety of tissues is a well established consequence of exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. Although localization of the induced protein within the lung has been described, the precise intracellular distribution of the enzyme is not clear. Analysis of tissue sections, microsomal proteins, and mRNA from lungs of treated and untreated rabbits established that P450 1A1 had been induced by treatment with TCDD. Rabbit lungs from animals treated with TCDD were examined with immunocytochemistry and in situ hybridization, to identify the cell types that contain P450 1A1 and those that contain mRNA encoding P450 1A1. Endothelial cells of the entire vascular bed of rabbit lung reacted markedly with anti-P450 1A1. Likewise, cells lining both arteries and veins, as well as capillary endothelial cells, reacted strongly with the cDNA probe for mRNA encoding P450 1A1. Clara cells at all levels of airway labeled prominently for both P-450 1A1 and P450 1A1 mRNA. In addition, type 2 cells, alveolar macrophages, and to a lesser degree, ciliated cells reacted with the cDNA probe. P450 reductase, which is required for P450 activity, has previously been identified in Clara cells, type 2 cells, and alveolar macrophages, but not in endothelium of rabbit lung. We have now obtained similar results for the localization of mRNA encoding P-450 reductase. This finding brings into question the function of P450 1A1 in endothelium. PMID- 1614409 TI - Effect of corticosteroids on the expression of cytochromes P450 and on cyclosporin A oxidase activity in primary cultures of human hepatocytes. AB - Prednisone, prednisolone, and methylprednisolone are currently administered in association with cyclosporin A in the postoperative treatment of transplant patients. The aim of this work was to evaluate the effects of these corticosteroids on the expression of several forms of cytochromes P450 (P450), including P450 1A2, 2D6, 2E1, and 3A, and on cyclosporin A oxidase activity in human liver. For this purpose, human hepatocytes prepared from lobectomies were maintained in culture in a serum-free medium, in collagen-coated dishes, for 96 144 hr, in the absence or presence of 50-100 microM corticosteroids, rifampicin, or dexamethasone. To mimic more closely the current clinical protocol, hepatocyte cultures were also co-treated with corticosteroids and cyclosporin A or ketoconazole (a selective inhibitor of P450 3A). Cyclosporin A oxidase activity, intracellular retention of cyclosporin A oxidized metabolites within hepatocytes, accumulation of P450 proteins and corresponding messages, and de novo synthesis and half-lives of these P450 were measured in parallel in these cultures. Our results, obtained from seven different hepatocyte cultures, showed that 1) dexamethasone and prednisone, but not prednisolone or methylprednisolone, were inducers of P450 3A, at the level of protein and mRNA accumulation, as well as of cyclosporin A oxidase activity, known to be predominantly catalyzed by these P450; 2) although corticosteroids are known to be metabolized in human liver, notably by P450 3A, partial or total inhibition of this P450 by cyclosporin or ketoconazole, respectively, did not affect the inducing efficiency of these molecules; 3) corticosteroids did not affect the half-life of P450 3A or the accumulation of other forms of P450, including 1A2, 2D6, and 2E1; 4) chronic treatment of cells with cyclosporin did not affect P450 3A accumulation; 5) corticosteroids were all competitive inhibitors of cyclosporin A oxidase in human liver microsomes, with Ki values of 61 +/- 12, 125 +/- 25, 190 +/- 38, and 210 +/ 42 microM for dexamethasone, prednisolone, prednisone, and methylprednisolone, respectively; and 6) chronic treatment of cells with corticosteroids did not influence the excretion of oxidized metabolites of cyclosporin from the cells. These results support most of clinical reports dealing with mutual interactions between cyclosporin A and corticosteroids. PMID- 1614410 TI - Different types of receptor interaction of peptide and nonpeptide angiotensin II antagonists revealed by receptor binding and functional studies. AB - The pharmacological effects of angiotensin II (AII) are potently inhibited by several peptide and recently synthesized nonpeptide AII receptor antagonists. The interaction of sarcosine1, isoleucine8-AII (sarile), sarcosine1,O-methyltyrosine4 AII (sarmesin), and the nonpeptide AII antagonists 2-n-butyl-4-chloro-5- hydroxymethyl-1-[(2'-(1H-tetrazole-5-yl)biphenyl-4-yl)- methyl]imidazole (DuP 753, Losartan potassium) and its metabolite 2-n-butyl-4-chloro-1-[(2'-(1H tetrazole-5-yl)biphenyl-4-yl)methyl]imidaz ole - 5-carboxylic acid (EXP3174) with AII binding sites was investigated in radioligand binding and functional studies. Sarile, sarmesin, DuP 753, and EXP3174 inhibited 125I-AII binding to rat lung tissue, with Ki values of 3.5, 16.1, 23.7, and 10.4 nM, respectively. The Hill coefficients of all displacement curves, except for sarile (nH, 1.45), were not significantly different from unity. In functional experiments using rabbit aorta, sarmesin and DuP 753 competitively inhibited the contractile response to AII, with pA2 values of 6.75 and 8.01, respectively. Sarile, in contrast, revealed noncompetitive antagonism, i.e., the maximum contractile force and the slope of the concentration-contractile force curve were significantly and concentration dependently depressed. The concentration-contractile response curve for AII was shifted to the right in a parallel fashion in the presence of EXP3174 (3 nM to 1 microM); however, the maximum contractile force was significantly decreased, by 24%. The marked noncompetitive antagonism of sarile (3 nM) was reversed in the presence of increasing concentrations of sarmesin (30 nM to 30 microM) or DuP 753 (10 nM to 1 microM), whereas in the presence of increasing concentrations of EXP3174 (3-300 nM) a 25% depression in maximum contractile force persisted. Moreover, the reduction of the maximum contractile force by EXP3174 (10 nM) was concentration-dependently restored in the presence of increasing concentrations of DuP 753 (10 nM to 1 microM), indicating interaction with the same binding site. Whereas sarile (0.3-10 nM) did not affect the 125I-AII binding capacity in radioligand saturation experiments, a 54% reduction of Bmax was observed in the presence of 100 nM EXP3174. The data provide evidence that all antagonists inhibit the functional response to AII by interacting with a common binding site at the receptor. The noncompetitive behavior of sarile seems to be due to slow dissociation from this receptor site. An additional mechanism must be postulated for EXP3174. An allosteric interaction with the receptor, as suggested by the reduction in Bmax, may be, at least in part, responsible for the nonclassical antagonism of this compound. PMID- 1614411 TI - [3H]pBC 264, a suitable probe for studying cholecystokinin-B receptors: binding characteristics in rodent brains and comparison with [3H]SNF 8702. AB - [3H]Propionyl-Tyr-(SO3H)-gNle-mGly-Trp-(NMe)Nle-Asp-Phe-NH2 ([3H]pBC 264) (98-100 Ci/mmol), a new peptidase-resistant cholecystokinin (CCK) agonist that is 1000 fold more potent for CCK-B than for CCK-A receptors, interacts, with a similar subnanomolar affinity, with a single class of binding sites (Kd, 0.15-0.2 nM) in brain membranes of mouse, rat, guinea pig, and cat, in Tris and Krebs buffers. The concentration of CCK-A receptors in rodent brain was estimated to be 8-10 fmol/mg of protein, by measurement of the Bmax values of the nonselective agonist [3H] propionyl-CCK8, with or without 10 nM pBC 264 to saturate CCK-B sites. In guinea pig and mouse brain, specific [3H]pBC 264 binding was not affected by NaCl and/or guanyl-5'-yl-imidodiphosphate. In contrast, in rat brain the affinity of [3H]pBC 264 was decreased and the maximal number of binding sites was increased by NaCl and the guanyl nucleotide or by alkaline treatment, suggesting that a proportion of CCK-B receptors are linked to guanine nucleotide-binding proteins. The Bmax of a CCK8 analog, [3H]SNF 8702, was higher (57 fmol/mg of protein) than that of [3H]pBC 264 (40 fmol/mg of protein) in guinea pig brain cortex but not in mouse brain. The relative potencies of various analogs differed among species. The CCK-B antagonist L365,260 was 18-, 30-, and 64-fold less potent than [3H]pBC 264 in guinea pig, mouse, and rat, respectively. PD 134308, a CCK-B antagonist, was 20-fold less potent in rat brain than in guinea pig brain. Likewise, the cyclic analog BC 254 displayed a 30- and 60-fold lower affinity for mouse and rat than for guinea pig brain preparations. Together, these results suggest the presence of CCK-B receptor subtypes. In all tissues, the specific binding of [3H]pBC 264 at its Kd values was very high (75-90%) and higher than that of the hydrophobic CCK-B probe [3H]SNF 8702 (approximately 50%). Therefore, unlike [3H]SNF 8702, [3H]pBC 264 can be used to study preparations with low receptor concentrations, such as rat brain, making this radiolabeled molecule the most appropriate ligand available to date for CCK-B receptor studies. PMID- 1614412 TI - Photoactivatable agonist of the nicotinic acetylcholine receptor: potential probe to characterize the structural transitions of the acetylcholine binding site in different states of the receptor. AB - The nicotinic acetylcholine receptor exhibits at least four different affinity states for agonists such as acetylcholine. In order to identify the structural changes occurring at or near the agonist binding site during the allosteric transitions, three photoactivatable compounds designed to display agonist activity were synthesized. Inhibition constants of these compounds for the cholinergic and the noncompetitive blocker binding sites were determined for the resting and the desensitized states of the receptor. Among these probes, two ligands, AC5 and AC7, displayed a high affinity for the agonist binding site and were poorly recognized by the binding site for noncompetitive blockers. Electrophysiological experiments revealed that these ligands behaved as agonists at low concentrations. We used these two compounds in photolabeling experiments and observed that they were able to inactivate the agonist binding site. Up to 50% of these sites were irreversibly inhibited, depending on the ligand, the irradiation conditions, and the selected receptor state. The compound with the most interesting properties (high affinity and selectivity for the acetylcholine binding site, as well as agonist activity and high photolabeling yield) is AC5, a structural analogue of the fluorescent agonist dansyl-C6-choline, which has been previously used to characterize the different states of the nicotinic receptor. After radioactive synthesis, [3H]AC5 was shown to label all four receptor subunits, in a protectable manner. This radioligand, thus, appears suitable for investigation of the dynamics of allosteric transitions occurring at the activated acetylcholine binding site. PMID- 1614413 TI - Stimulation of monooxygenation and conjugation after liver transplantation in the rat: involvement of Kupffer cells. AB - The success rate of liver transplantation has improved markedly during the last few years and, although this patient population receives multiple drug therapies, the effect of liver transplantation on drug metabolism has been studied very little. Therefore, the purpose of this study was to assess the metabolism of model drug substrates after liver transplantation in the rat. Rat livers were stored for 4 hr in cold Euro-Collins solution, transplanted orthotopically, and then perfused 2 hr later with oxygenated Krebs-Henseleit buffer, using a nonrecirculating system. Rates of monooxygenation of the model compound p nitroanisole, conjugation of p-nitrophenol, and uptake of oxygen were measured. All parameters studied were elevated significantly, by nearly 2-fold, by transplantation. Specifically, monooxygenation was increased from 2.9 +/- 0.2 to 5.1 +/- 0.4 mumol/g/hr, conjugation was elevated from 3.3 +/- 0.6 to 7.7 +/- 0.1 mumol/g/hr, and O2 uptake was stimulated from basal values of 114 to 197 mumol/g/hr. Transplantation did not, however, alter rates of monooxygenation and conjugation in isolated microsomes supplemented with excess cofactor. When donor rats were pretreated with the Kupffer cell toxicant gadolinium chloride (10 mg/kg, intravenously) 30 hr before liver storage, the elevation after transplantation in all parameters studied was prevented. Depletion of carbohydrate reserves by fasting of donor rats did not prevent stimulation of monooxygenation and conjugation. On the other hand, urea synthesis from ammonium chloride, a process dependent on mitochondrial NADPH, was increased and monooxygenation was diminished after transplantation, suggesting the involvement of mitochondria in this phenomenon. Indeed, mitochondria isolated 2 hr postoperatively exhibited significantly elevated respiratory control ratios and higher state 3 rates of respiration. Taken together, these data support the hypothesis that Kupffer cells, activated by transplantation, release mediators that stimulate mitochondria in parenchymal cells and enhance drug metabolism by increasing cofactor supply (e.g., NADPH for monooxygenation and UDP-glucuronic acid for glucuronidation). PMID- 1614414 TI - Effects of vitamin E on the killing of cultured hepatocytes by tert-butyl hydroperoxide. AB - The disposition of vitamin E was examined in cultured rat hepatocytes intoxicated with tert-butyl hydroperoxide (TBHP). Culturing of the cells overnight (18-20 hr) with approximately 60 nM alpha-tocopherol (alpha-T) equivalents [Williams' E medium, 18 nM tocopherol phosphate (alpha-TP), 9% fetal calf serum, 43 nM alpha T] resulted in a content of alpha-T that was 16% of the concentration of vitamin E measured in freshly isolated hepatocytes. Supplementation of the medium with 1 microM alpha-TP maintained the alpha-T concentration of the cultured cells at the level of freshly isolated hepatocytes. Supplemented hepatocytes exposed to TBHP showed decreased lipid peroxidation and delayed cell killing, compared with hepatocytes not cultured overnight with alpha-TP. Killing of the supplemented cells by TBHP was accompanied by a loss of alpha-T. Pretreatment of supplemented hepatocytes with the iron chelator deferoxamine prevented much of the loss of alpha-T. At the same time, deferoxamine inhibited both the lipid peroxidation and cell killing. The antioxidant N,N'-diphenyl-1,4-phenylenediamine reduced the loss of alpha-T and significantly decreased lipid peroxidation. In the presence of N,N'-diphenyl-1,4-phenylenediamine, cell killing was delayed by 15 min and reduced in extent. Overnight supplementation of hepatocytes with nonesterified alpha-T, or vitamin E esters other than alpha-TP, similarly rendered the cells less sensitive to TBHP. The nonesterified alpha-T produced a higher cell associated vitamin E concentration than did the esters; however, nonesterified alpha-T did not result in greater protection against TBHP. These data indicate that the mechanisms of the cell killing by TBHP are the same in cultured hepatocytes that contain low or physiological concentrations of vitamin E. PMID- 1614415 TI - Helicase inhibition by anthracycline anticancer agents. AB - Helicases are essential to both DNA replication and transcription because they separate double-stranded DNA, preparing the single strands for replication or transcription. Because the anti-cancer anthracycline antibiotics stabilize double stranded DNA primarily by their intercalative binding, we expected the intercalated antibiotics to interfere with helicase action. We examined anthracycline antibiotic effects on SV40 large T antigen helicase activity, using a duplex DNA helicase substrate of 32P-labeled 17-mer annealed to complementary M13mp19(+) circular single-stranded DNA. The T antigen helicase activity was potently inhibited by the anthracycline antibiotics. The T antigen helicase IC50 values for the anthracycline antibiotics were as follows: nogalamycin, 2 x 10(-7) M; daunorubicin, 4 x 10(-7) M; doxorubicin, 4 x 10(-7) M; idarubicin, 1.8 x 10( 6) M; 4'-epidoxorubicin, 2 x 10(-6) M; aclacinomycin, 4 x 10(-6) M; and menogaril, 6 x 10(-6) M. Partially purified helicases from HeLa cells and murine mammary carcinoma FM3A cells also were potently inhibited by doxorubicin, with IC50 values of 4 x 10(-7) M and 9 x 10(-7) M, respectively. Because the abundance, specificities, and types of helicases vary in the cell, this site of action for anthracycline antibiotics may help explain anthracycline potency, drug specificity for DNA or RNA inhibition, and some types of cellular resistance to these drugs. PMID- 1614416 TI - Transfection of human 5-hydroxytryptamine1A receptors in NIH-3T3 fibroblasts: effects of increasing receptor density on the coupling of 5-hydroxytryptamine1A receptors to adenylyl cyclase. AB - Human serotonin [5-hydroxytryptamine (5-HT)1A] receptors have been transfected in NIH-3T3 cells, and their pharmacology and coupling to adenylyl cyclase have been analyzed. Three cellular preparations were used, 1) monoclonal cell lines (clones 6, 2B, and 4B), expressing 45, 280, and 500 fmol of 5-HT1A receptors/mg of protein, respectively; 2) clones 6, 2B, and 4B in which the concentration of 5 HT1A receptors was increased after stimulation of the glucocorticoid-inducible promoter with dexamethasone; and 3) polyclonal cell lines that expressed an increasing amount of 5-HT1A receptor as a function of cell passage. The transfected 5-HT1A receptors inhibited basal, forskolin-stimulated, and isoproterenol-stimulated adenylyl cyclase. The inhibition was dependent on the receptor density expressed, increasing from 60% at low density (45 fmol/mg) to 90% at a density higher than 280 fmol/mg. The pharmacology of the 5-HT1A receptor was studied, with particular attention being paid to the behavior of some agonists. These pharmacological characteristics are similar to those of 5-HT1A receptors in hippocampus but different from those of 5-HT1A in cerebral cortex. Analysis of the potencies and efficacies of the full agonist 5-HT and the partial agonist ipsapirone, as a function of receptor density in the three cellular populations used, revealed that 1) the efficacies of the full and partial agonists increased with the receptor density; 2) the EC50 values of the full and partial agonists were not shifted to the left when the receptor density was increased (based on the increase in efficacy and considering the classical pharmacological models of receptor-drug action, a 9-10-fold shift was expected); and 3) the ratio between the efficacies of the full agonist 5-HT and the partial agonist ipsapirone was not modified when the receptor concentration was increased or when the GTP-binding protein availability was decreased. The results indicate that neither the classical nor the operational model of drug-receptor action can be used to describe the coupling of 5-HT1A receptors to adenylyl cyclase in transfected NIH-3T3 cells. One of the explanations could be that 5-HT1A receptors and GTP-binding proteins are coupled in functional domains (almost precoupled), rather than distributed in homogeneous compartments in which they are free to diffuse. PMID- 1614417 TI - Molecular mechanism of RU 486 action: a review. PMID- 1614418 TI - Polyamines in liver and their influence on chromatin condensation after 17-beta estradiol treatment of Atlantic salmon. AB - Atlantic salmon (Salmo salar) were treated with 17-beta estradiol to induce vitellogenin synthesis in liver. This led to an increase in liver wet weight and total DNA. After incubation with micrococcal nuclease (EC 3.1.31.1) less soluble chromatin was obtained from nuclei of the estradiol treated than the control fish, but active gene regions were solubilized by the nuclease. Thus, in the estradiol treated fish soluble mononucleosomes contained hybridizable vitellogenin gene sequences. As a result of estradiol treatment the content in total liver of putrescine rose 3-fold, that of spermidine 2-fold, while spermine was unchanged. In muscle no significant changes were observed. The regulatory functions of polyamines during gene expression were investigated by binding (14C)spermine to isolated liver nuclei depleted of endogenous polyamines. The number of binding sites was higher in nuclei of estradiol treated than control fish. (14C)spermine associated preferentially with micrococcal nuclease insensitive chromatin. Thus, the high content of putrescine and spermidine in liver supported the view of polyamine accumulation in proliferating tissues. The preferential binding to condensed chromatin indicated a stabilizing effect of polyamines on the organization of inactive chromatin structures. PMID- 1614419 TI - Trypanosoma cruzi glycoprotein 72: immunological analysis and cellular localization. AB - Two monoclonal antibodies were used to biochemically characterize glycoprotein 72 (GP72) from Trypanosoma cruzi and to localize the protein in live and fixed parasites by indirect immunofluorescence and in thin section of parasites by immunogold electron microscopy. GP72 was shown in immunoblots to be specific for the epimastigote stage; the protein could not be detected in trypomastigotes. Each antibody reacted with a different epitope on the glycoprotein and deglycosylation of GP72 ablated reactivity with one of the antibodies. Indirect immunofluorescence and electron microscopic evaluation of parasite associated gold particles showed the presence of GP72 in the cell surface membrane including the flagellar pocket and the cytostome. In addition, cytoplasmic membrane vesicles of the endosomal-lysosomal system stained intensely. PMID- 1614420 TI - Heparin releasable and nonreleasable forms of heparan sulfate proteoglycan are found on the surfaces of cultured porcine aortic endothelial cells. AB - Evidence suggests that endothelial cell layer heparan sulfate proteoglycans include a variety of different sized molecules which most likely contain different protein cores. In the present report, approximately half of endothelial cell surface associated heparan sulfate proteoglycan is shown to be releasable with soluble heparin. The remaining cell surface heparan sulfate proteoglycan, as well as extracellular matrix heparan sulfate proteoglycan, cannot be removed from the cells with heparin. The heparin nonreleasable cell surface proteoglycan can be released by membrane disrupting agents and is able to intercalate into liposomes. When the heparin releasable and nonreleasable cell surface heparan sulfate proteoglycans are compared, differences in proteoglycan size are also evident. Furthermore, the intact heparin releasable heparan sulfate proteoglycan is closer in size to proteoglycans isolated from the extracellular matrix and from growth medium than to that which is heparin nonreleasable. These data indicate that cultured porcine aortic endothelial cells contain at least two distinct types of cell surface heparan sulfate proteoglycans, one of which appears to be associated with the cells through its glycosaminoglycan chains. The other (which is more tightly associated) is probably linked via a membrane intercalated protein core. PMID- 1614421 TI - Stimulation of insulin release by isosmolar addition of permeant molecules. AB - Pancreatic beta-cells are known to respond to hyposmolar stress by releasing insulin. It was evident from perifusion studies using islet cells from ob/ob-mice mixed with polyacrylamide beads that a similar type of secretory response can be obtained by isosmolar addition of 10-25 mM of the rapidly penetrating urea molecule. There was no effect with hyperosmolar addition of urea. The urea induced insulin release differed from the ordinary stimulation of secretion in not disappearing but being more pronounced after previous heating to 45 degrees C or removal of extracellular Ca2+. Isosmolar urea was exceptional as an insulin secretagogue in being effective also in the presence of the alpha 2-adrenergic agonist clonidine or when lowering the temperature to 24 degrees C. Further support for the idea that isosmolar addition of rapidly penetrating molecules induces insulin release was obtained by testing non-metabolizable glucose analogues. Whereas 25 mM 3-O-methyl-D-glucose doubled the secretory rate within 4 min, the non-permeant L-glucose had only a slight initial action. When not compensating for the alterations of the medium osmolarity 3-O-methyl-D-glucose was without effect. Although expansion of beta-cells cannot explain the existence of a pronounced initial secretory response to D-glucose it may under certain conditions contribute to the stimulatory effects of the sugar. PMID- 1614422 TI - Changes in lipid content and composition during the development of N nitrosodiethylamine induced hepatocarcinoma. AB - Alterations in lipid content and composition in the N-nitrosodiethylamine-induced hepatocarcinoma were investigated. Rats were administered with N nitrosodiethylamine in the drinking water for 12 weeks followed by normal tap water for another 6 weeks. The cholesterol content in the liver was increased shortly after the administration of N-nitrosodiethylamine and remained elevated after the removal of the nitrosoamine from the water. The phosphatidylethanolamine level was elevated during N-nitrosodiethylamine administration with a concomitant reduction in phosphatidylcholine level. Lysophosphatidylcholine and sphingomyelin levels were increased during the last four weeks of the study. The level of phosphatidylinositol was substantially reduced after eight weeks of N-nitrosodiethylamine treatment, and remained low during the post-treatment period. We postulate that changes in lysophosphatidylcholine and sphingomyelin may be a compensatory mechanism for maintaining the asymmetrical distribution of choline-containing lipids in the outer leaflet of the membrane. The elevated level of cholesterol may be a useful indicator for the early detection of N-nitrosodiethylamine-induced hepatocarcinoma. PMID- 1614424 TI - Keys to regeneration. Proceedings of the European Conference on Tissue and Post Traumatic Regeneration. Geneva, September 3-7, 1990. PMID- 1614425 TI - The foundations of contemporary regeneration research: historical perspectives. PMID- 1614426 TI - Axonal release of transferrin in peripheral nerves of axolotls during regeneration. PMID- 1614423 TI - Dipyridamole stimulates types II cAMP-dependent protein kinase in vitro. AB - Dipyridamole activates in vitro type II cAMP-dependent protein kinase. This agent stimulates the autophosphorylation of the regulatory subunit in the presence of cAMP but not so in the absence of the cyclic nucleotide. The activation was also observed with exogenous substrates such as casein, histone 2A and MAP2. This stimulation did not seem to be related to the cAMP binding to the R II subunit of the enzyme. Competition binding experiments showed that dipyridamole does not compete with adenosine for the A1 receptor. The results suggest that the reported regulatory properties of dipyridamole on lipid metabolism (Gonzalez-Nicolas et al. Int J Biochem 21: 883-888, 1989) might be mediated through a direct action- an activation--on the catalytic subunit of a cAMP-dependent protein kinase. PMID- 1614427 TI - Characterization of fibroblast growth factor binding in regenerating limb blastemas of axolotls. PMID- 1614428 TI - Extraction of the WE3 antigen and comparison of reactivities of mAbs WE3 and WE4 in adult newt regenerate epithelium and body tissues. PMID- 1614429 TI - Activation of genes coding for gamma-crystallins during lens regeneration in the newt. PMID- 1614430 TI - Pattern perturbation in Xenopus laevis forelimb regenerates following treatment with retinoic acid and carrier media. PMID- 1614431 TI - Observations on digit regeneration in the amphibian Triturus cristatus after 180 degrees rotation of digit blastemata. PMID- 1614432 TI - On the completeness of skin regeneration and reorganization of scars in warm blooded animals. PMID- 1614433 TI - Properties of the donor muscle determine the characteristics of regenerated avian skeletal muscle. PMID- 1614434 TI - Muscle regeneration and aging. PMID- 1614435 TI - Regeneration of connective tissue in different organs of xenogeneic mouse radiation chimeras. PMID- 1614436 TI - Regeneration of hemopoietic and connective tissues. PMID- 1614437 TI - Lymphoid cell-derived humoral factors as possible mediators in regeneration information transfer. PMID- 1614439 TI - Aluminium concentration in nuclei of regenerating rat liver cells. A study by analytical ion microscopy. PMID- 1614438 TI - A model of hepatic regeneration and carcinogenesis due to total liver cell injury induced by dipin and partial hepatectomy. PMID- 1614440 TI - Regeneration of the aquapharyngeal complex in the holothurian Eupentacta fraudatrix (Holothuroidea, Dendrochirota). PMID- 1614441 TI - Regeneration of digestive tube in holothurians Stichopus japonicus and Eupentacta fraudatrix. PMID- 1614442 TI - The fish fin regenerate. PMID- 1614443 TI - Effects of amputation through primary forelimb regenerates and delayed denervation of the secondary blastemata on the continuation of regeneration in adult newts. PMID- 1614444 TI - [Surfactant homeostasis--principles for surfactant substitution therapy]. PMID- 1614445 TI - [Pediatric tracheostomy care]. AB - Long term tracheostomy has become a rare caregiving problem in Paediatrics, but remains the only therapeutic strategy for a spectrum of complex anomalies of the paediatric airway. The present state-of-the-art article describes the practical routine of tracheostomy care as developed in the Paediatric Department of Graz. Commencing with indications for tracheostomy and a brief comment on relevant operations, it discusses routine and special tracheostomy tubes, valves, and other accessory devices. One chapter on specialised care is focussed on the paediatric airway, another more general one is concerned with the tracheostomized child. Then follows teaching tracheostomy care to parents; the article ends with a discussion of control investigations and decannulation. PMID- 1614447 TI - [Pachygyria and laminar heterotopic tissue. A rare case of unique expression of a neuronal migration disorder in twins]. AB - We report of 16 year old twinsisters with a neuronal migration disorder, twin I with mental retardation and focal epileptic seizures on MRI showed general pachygyria, laminar subcortical heterotopia and mildly dilated lateral ventricles, whereas twin II whose first symptom was a cerebral seizure only showed a focal pachygyria and laminar subcortical heterotopia; the location of pachygyria corresponded to the epileptogenic focus. The morphological expression seems to correspond with the severeness of the clinical features. Genetic as well as exogenic factors must be assumed to be causative for the migration anomalies. PMID- 1614446 TI - [48,XXYY syndrome in a boy with essential tremor. Comparison with 120 cases from the literature]. AB - We report on a 14 year-old boy with 48,XXYY karyotype, presenting with essential tremor and a slight retardation of psychomotor development. In contrast to other cases with 48,XXYY syndrome, this pubertal patient has testicles of normal size, has small stature and shows no behavioural disturbances. We compared our patient with 120 other published cases. PMID- 1614448 TI - [Growth hormone therapy in STH deficiency with immunologic deficiency and chromosome fragility]. AB - A 8 year old boy with short stature, low height velocity, mental retardation, cutaneous abnormalities, common variable immunodeficiency and increased chromosomal instability is described. In this patient growth hormone deficiency could be demonstrated by several stimulation tests. Growth hormone treatment increased growth rate from 4 cm/year before therapy to 7.8 cm in the first and 7.1 cm in the second year of treatment. Under therapy no effect on the immunological reactivity could be observed. PMID- 1614449 TI - [Mucociliary clearance in childhood]. AB - AIM OF THE STUDY: A new, nearly monodisperse human serum albumin particle produced by air-pressure-nebulization was inhaled by children and lung-transplant patients. METHOD: After inhalation of the particles obtained with an air-pressure nebulizer, the initial deposition pattern showed a marked tracheobronchial deposition which could be reproducibly obtained without a special breathing technique, the alveolar deposition being not higher than 10%. With the use of 99mTc, the radiation exposure is limited to a level which is low enough for children, but images can be taken up to 24 hrs later. Further parameters for in vivo characterization of the mucociliary function are the 24 h retention pattern and the velocity of particle motion in the trachea. RESULTS: Within the first 45 minutes, the global clearance rate was 51% in healthy children, which is rather high in comparison with the literature, most likely due to size of particles and the selection of patients with a mean age of 10.7 years. In ciliary dysfunction, the initial clearance rate was 16% and 46% within 24 h. CONCLUSIONS: With simplification of the preparation, application, and examination technique, this method is to be used in children, so that a wider use can be anticipated. The normally fast initial elimination of particles allows quick differentiation of normal and impaired ciliary function. PMID- 1614450 TI - [Cerebral Doppler measurements in risk newborn infants do not have a prognostic value]. AB - PROBLEM: The prognostic value of cerebral doppler for the neonatal and the developmental prognosis was studied. METHODS: A prospective longitudinal study on 175 newborns at risk was performed. The blood flow velocities were recorded transcranially in the middle cerebral, posterior cerebral and internal carotid artery on day 1, 3-5 and 8-10 of life. Neonatal mortality and cerebral sonography gave the criteria for neonatal prognosis. Developmental prognosis was determined at a corrected age of 9 months by neurological examination and Griffth's test. RESULTS: In 60 neonates abnormal flow velocities were obtained at least at one recording. Ultrasound revealed cerebral hemorrhage in 20, hypoxic-ischemic encephalopathy in 5 children. 14 infants died during the neonatal period, 5 in the following months. Premature babies with birth weights below 1501 g and abnormal flow velocities presented more cerebral hemorrhages and deaths than those with normal flow velocities. At the age of 9 months a slight handicap was observed in 10, a severe handicap in 6 of the surviving 156 infants. The majority of infants with abnormal neonatal doppler-recording had a normal neurodevelopmental status. CONSEQUENCE: Cerebral doppler seems to be of little value to determine the prognosis of newborns at risk. PMID- 1614451 TI - [Is the Crede eye disease prevention with silver nitrate still necessary. Position of the German-Austrian Society of Neonatology and Pediatric Intensive Care]. PMID- 1614452 TI - [In memory of Arvo H. Ylppo]. PMID- 1614453 TI - [Diagnosis and therapy of anemia in childhood. Part 1. Differential diagnosis, hypoplastic anemia, thalassemia]. PMID- 1614454 TI - [Kawasaki syndrome. Association with exposure to carpet shampoo and successful therapy with immunoglobulins in the second week of the illness]. AB - A male infant and a three year old girl, both with acute febrile illness, were admitted to our hospital for suspected meningitis/sepsis and gastroenteritis/severe viral infection, respectively. Both showed all six principal features of Kawasaki syndrome and revealed several other symptoms and laboratory findings commonly associated with the disease. The infant had multiple coronary aneurysms. The girl developed ascites, pancreatitis and iritis, all of which are seldomly recognized symptoms of the Kawasaki syndrome. The prompt and satisfactory therapeutic responses of both patients to the combined therapy consisting of oral acetylsalicylic acid (50-100 mg/kg b.w./d) and intravenous gamma-globuline (400 mg/kg b.w./d) at the eight and even eleventh day of illness support the use of gamma-globuline therapy beyond the first week of the disease. Prior to their illnesses both children had been exposed to carpet shampoo, an agent which has been repeatedly associated with an increased risk of Kawasaki syndrome. PMID- 1614455 TI - [Pyromania and enuresis. Multifactorial causes require multidimensional treatment concepts]. AB - The abilities to control the voiding of the bladder and to act competently in dealing with fire are important factors of the normal development of children. Unfavourable conditional constellations in the socio-emotional, cognitive, or physical realm can cause developmental defects which manifest themselves in certain target symptoms, for instance Pyromania and Enuresis. The importance of multifactorial etiological models will be illustrated by a case report of a boy displaying symptoms of Pyromania and Enuresis nocturna. The analysis of the specific conditions of the case studied results in the appropriate multidimensional treatment concept. PMID- 1614456 TI - [Neonatal variant of Bartter syndrome]. AB - A male preterm infant of 32 weeks of gestation with history of severe polyhydramnios during pregnancy presented soon after birth with polyuria with initial sodium chloride loss subsequently followed by increasing potassium loss. After manifestation of hypokalaemia, hypochloraemia, alkalosis and high urinary prostaglandin concentrations, the diagnosis of the neonatal variant of Bartter's syndrome was made. The treatment consisted of administered of large amounts of fluid with sodium chloride and potassium supplementation and indomethacin (1.5 to 2 mg/kg per day). PMID- 1614457 TI - [Tumors of the adrenal gland and lumbar sympathetic chain. Differential ultrasound diagnosis in childhood]. AB - In a retrospective study from 1979 to 1989 17 tumors of the sympathic chain and the adrenal gland were analysed according to typical sonographic patterns. 13 tumors (10 neuroblastomas, 2 pheochromocytomas, 1 adenoma of the adrenal gland) were localized within the abdomen, 4 tumors (3 neuroblastomas, 1 ganglioneuroma) originated from the mediastinum. Neuroblastomas usually were great suprarenal masses with bad delineation and inhomogenous increased echogenicity in comparison with the liver. In more than 50% calcifications occurred, whereas cysts (15%) could rarely be found. The upper pole of the ipsilateral kidney usually was compressed and displaced caudally and laterally. The great intraabdominal vessels were usually displaced anteriorly and to the opposite side. The disturbed flow within the compressed intraabdominal vessels could reliably be shown by colour Doppler sonography as well as tumor vascularity. The 2 pheochromocytomas as well as the ganglioneuroma and the adenoma of the adrenal gland were round or oval, well delineated nodules with homogeneous liver like echogenicity. According to their typical sonographic patterns tumors of adrenal gland and sympathic chain can be differentiated from each other as well as from kidney tumors. PMID- 1614458 TI - [Determination of hydrogen in expiratory air of premature infants in suspected necrotizing enterocolitis]. AB - BACKGROUND: Breath hydrogen (H2) analysis has been recommended for the differential diagnosis between necrotizing enterocolitis and transient feeding intolerance. METHODS: We performed 360 breath H2 analyses in 32 unselected premature babies by use of an electrochemical method. RESULTS: All babies on oral feedings excreted H2. The concentration of H2 in expired air was extremely variable and often high even in well premature babies. Antibiotic medication (other than penicillin G alone) inhibited breath hydrogen excretion. CONCLUSIONS: Breath hydrogen analysis can be used as a diagnostic tool for necrotizing enterocolitis if performed in a symptomatic child on oral feedings prior to the initiation of antibiotic therapy. PMID- 1614459 TI - [Reference values for IgE concentration in serum of children. Method: ImmunoCAP FEIA system]. AB - Age specific IgE reference values were determined in serum of 224 children by the aid of the ImmunoCAP fluorescence enzyme immunoassay method. RESULTS: Cord blood: less than 0.35 kU/l; Till 0.5 year: less than 2.0 kU/l; 0.5-2 years: up to 3.8 kU/l; 2-5 years: up to 16.0 kU/l; 5-8 years: up to 26.2 kU/l; 8-12 years: up to 34.6 kU/l; 12-16 years: up to 26.3 kU/l. These IgE reference values can be used for the diagnosis of pathological elevated IgE concentrations in serum of children. PMID- 1614460 TI - [Endocrinologic disorders in deletion of chromosome 18]. AB - Patients suffering from deletions of chromosome 18 (p-, q-) show regularly short stature. Endocrinological investigations were performed to prove if short stature is due to pituitary insufficiency. In three female patients with deletions of chromosome 18 and retarded bone age serum growth hormone was investigated after insulin induced hypoglycemia, after glucagon-propranolol and after stimulation with growth hormone releasing hormone. Thyroid function, gonadal function and adrenal function were investigated too. All three patients showed growth hormone deficiency. In one patient there were found in addition hypothyroidism and gonadotrophine deficiency as well. In conclusion growth failure in some patients with deletions of chromosome 18 seems to due to pituitary insufficiency. In these patients treatment with recombinant growth hormone may increase growth velocity. PMID- 1614461 TI - [Juvenile chronic leukemia and chronic myelomonocytic leukemia. Experiences with bone marrow transplantation in childhood in 5 cases]. AB - Chronic leukemias of early childhood (JCML/CMML) are rare malignant diseases for which effective regimens of chemotherapy have not been established. However, some of these patients may be cured by BMT. We report on 4 children with JCML and one child with CMML undergoing BMT from HLA-identical siblings and from matched unrelated donors. 3 of 5 patients are disease-free 9 to 37 months post BMT. According to our observations an effective reduction of blastic cells before BMT seems to be necessary for a sustained remission of these diseases. This reduction can be reached by intensive chemotherapy and by splenectomy before BMT. Moreover, we stress the need for total body irradiation (TBI) during BMT in order to eradicate residual malignant cells. PMID- 1614462 TI - Intravenous immune globulin for the prevention of nosocomial infection in low birth-weight neonates. The Multicenter Group for the Study of Immune Globulin in Neonates. AB - BACKGROUND: Nosocomial infection is a major risk for premature infants with very low birth weights. One reason for their susceptibility to infection may be antibody deficiency, since there is little transfer of maternal IgG to the fetus before 32 weeks' gestation. METHODS: We conducted a multicenter, double-blind study of neonates weighing 500 to 1750 g at birth. A total of 588 neonates were randomly assigned, with stratification for birth weight, to receive periodic intravenous infusions of either immune globulin (500 mg per kilogram of body weight per day) or a placebo. Mortality, morbidity, and nosocomial infection during the next 56 days were assessed. RESULTS: The infusions were well tolerated; mild, reversible adverse reactions occurred in five infants in each group. There was a significant reduction in the risk of a first nosocomial infection in the recipients of immune globulin as compared with the placebo recipients (relative risk, 0.7; 95 percent confidence interval, 0.5 to 0.9). About 85 percent of the nosocomial infections were bacterial; the majority of these were caused by coagulase-negative staphylococci or Staphylococcus aureus. The neonates who received immune globulin had fewer mean days of hospitalization than the controls (62 vs. 68, P = 0.15); among the infants with infections, the difference in the mean length of the hospital stay was even greater (80 days vs. 101 days, P = 0.02). CONCLUSIONS: For premature infants weighing between 500 and 1750 g at birth, treatment with intravenous infusions of immune globulin is safe and reduces the risk of nosocomial infection. PMID- 1614463 TI - Preserved insulin secretion and insulin independence in recipients of islet autografts. AB - BACKGROUND: Transplantation of pancreatic islets, rather than whole pancreas, has been introduced as a treatment for diabetes mellitus. We studied five patients ranging in age from 12 to 37 years who had severe chronic pancreatitis for which they underwent total pancreatectomy followed by isolation and hepatic transplantation of their own islets. METHODS: All patients had remained insulin independent for 1 to 7 1/2 years after transplantation. The numbers of islets transplanted ranged from 110,000 to 412,000. Islet function was assessed by measuring the plasma insulin responses to intravenous glucose and arginine and the plasma glucagon responses to hypoglycemia and arginine. In one patient, islet function was studied during catheterization of the hepatic vein, portal vein, and splenic artery and by analysis of a liver-biopsy specimen. RESULTS: After transplantation, the mean (+/- SD) fasting plasma glucose concentration was 122 +/- 47 mg per deciliter (6.8 +/- 2.6 mmol per liter) and the hemoglobin A1c concentration was 6.0 +/- 0.8 percent in the five patients. The values were most abnormal--214 mg per deciliter (11.9 mmol per liter) and 7.3 percent, respectively--in the patient who received only 110,000 islets. The acute plasma insulin responses to glucose and to arginine in the five patients were 23 +/- 13 and 26 +/- 10 microU per milliliter (168 +/- 94 and 184 +/- 70 pmol per liter), respectively, as compared with 58 +/- 6 and 37 +/- 8 microU per milliliter (416 +/- 44 and 267 +/- 61 pmol per liter) in the normal subjects. The peak plasma glucagon responses to insulin and arginine were 21 +/- 4 and 65 +/- 36 pg per milliliter, respectively, as compared with 125 +/- 28 and 156 +/- 99 pg per milliliter in the normal subjects. All five patients had plasma epinephrine but not pancreatic polypeptide responses to hypoglycemia. The results of the hepatic vein catheterization in one patient indicated that the transplanted islets released insulin and glucagon in response to arginine. Immunoperoxidase staining of this patient's liver-biopsy specimen showed that the islets contained insulin, glucagon, and somatostatin but not pancreatic polypeptide. CONCLUSIONS: Intrahepatic transplantation of as few as 265,000 islets can result in the release of insulin and glucagon at appropriate times and in prolonged periods of insulin independence. PMID- 1614465 TI - Cumulative meta-analysis of therapeutic trials for myocardial infarction. AB - BACKGROUND: The large volume of published randomized, controlled trials has led to a need for meta-analyses to track therapeutic advances. Performing a new meta analysis whenever the results of a new trial of a particular therapy are published permits the study of trends in efficacy and makes it possible to determine when a new treatment appears to be significantly effective or deleterious. We describe the use of such a procedure, cumulative meta-analysis, to assess therapeutic trials among patients with myocardial infarction. METHODS: We performed cumulative meta-analyses of clinical trials that evaluated 15 treatments and preventive measures for acute myocardial infarction. RESULTS: An example of this method is its application to the use of intravenous streptokinase as thrombolytic therapy for acute infarction. Thirty-three trials evaluating this therapy were performed between 1959 and 1988. We found that a consistent, statistically significant reduction in total mortality (odds ratios, 0.74; 95 percent confidence interval, 0.59 to 0.92) was achieved in 1973, after only eight trials involving 2432 patients had been completed. The results of the 25 subsequent trials, which enrolled an additional 34,542 patients through 1988, had little or no effect on the odds ratio establishing efficacy, but simply narrowed the 95 percent confidence interval. In particular, two very large trials, the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico trial in 1986 (11,712 patients) and the Second International Study of Infarct Survival trial in 1988 (17,187 patients) did not modify the already established evidence of efficacy. We used a similar approach to study the accumulating evidence of efficacy (or lack of efficacy) of 14 other therapies and preventive measures for myocardial infarction. CONCLUSIONS: Cumulative meta-analysis of therapeutic trials facilitates the determination of clinical efficacy and harm and may be helpful in tracking trials, planning future trials, and making clinical recommendations for therapy. PMID- 1614466 TI - Moricizine. PMID- 1614464 TI - Prophylactic intravenous administration of standard immune globulin as compared with core-lipopolysaccharide immune globulin in patients at high risk of postsurgical infection. AB - BACKGROUND: Infections and their sequelae are a major cause of death among patients admitted to the surgical intensive care unit (ICU). Studies of passive immunotherapy with standard intravenous immune globulin and hyperimmune globulin directed against gram-negative core lipopolysaccharide to prevent gram-negative infections and their serious systemic complications have had equivocal results in such patients. METHODS: We performed a double-blind study to assess the efficacy of standard immune globulin and core-lipopolysaccharide hyperimmune globulin in preventing infections in surgical patients at high risk. The patients received standard immune globulin (400 mg per kilogram of body weight), hyperimmune globulin (400 mg per kilogram), or placebo (25 percent albumin, 8 ml per kilogram) weekly, for a maximum of four doses while in the ICU. RESULTS: A total of 352 patients were enrolled, and 329 could be evaluated. The number of patients in whom infections developed was significantly lower in the group receiving standard immune globulin than in the placebo group (36 of 109 vs. 53 of 112 patients, P = 0.03), as was the incidence of pneumonia (15 vs. 30 cases, P = 0.04), especially pneumonia due to gram-negative bacteria (5 vs. 16 cases, P = 0.02). The number of days spent in the ICU and the total days spent in the hospital were lower in the standard immune globulin group (medians of 2 and 7.5 days fewer; P = 0.02 and 0.06, respectively). In contrast, the hyperimmune globulin had no detectable prophylactic effect on infections (50 of 108 patients, with 25 cases of pneumonia). The rate of systemic infections and shock was similar in the three study groups, and hospital mortality did not differ significantly among them. CONCLUSIONS: Intravenous immune globulin given prophylactically to selected high-risk patients in the surgical ICU can reduce the incidence of infection. Core-lipopolysaccharide hyperimmune globulin is not effective in preventing gram-negative infections and their systemic complications. PMID- 1614467 TI - Case records of the Massachusetts General Hospital. Case 30-1992. Progressive neurodegenerative disease in a young boy. PMID- 1614468 TI - Immune globulin to prevent nosocomial infections. PMID- 1614469 TI - Perspectives in pancreatic and islet transplantation. PMID- 1614470 TI - Clinical trials and meta-analysis. What do they do for us? PMID- 1614472 TI - Dyslexia. PMID- 1614471 TI - Underinsurance in America. PMID- 1614474 TI - Dyslexia. PMID- 1614473 TI - Dyslexia. PMID- 1614475 TI - Dyslexia. PMID- 1614476 TI - Corticosteroids in the treatment of optic neuritis. PMID- 1614477 TI - Corticosteroids in the treatment of optic neuritis. PMID- 1614478 TI - Corticosteroids in the treatment of optic neuritis. PMID- 1614479 TI - Glucocorticoid therapy and pituitary-adrenal responses to corticotropin-releasing hormone. PMID- 1614480 TI - Glucocorticoid therapy and pituitary-adrenal responses to corticotropin-releasing hormone. PMID- 1614481 TI - Glucocorticoid therapy and pituitary-adrenal responses to corticotropin-releasing hormone. PMID- 1614482 TI - Calcitriol or calcium for postmenopausal osteoporosis. PMID- 1614483 TI - Calcitriol or calcium for postmenopausal osteoporosis. PMID- 1614484 TI - Prednisolone in severe alcoholic hepatitis. PMID- 1614485 TI - Aspirin to prevent stroke in nonrheumatic atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators. PMID- 1614486 TI - Gestational versus genetic mothers. PMID- 1614487 TI - Gestational versus genetic mothers. PMID- 1614488 TI - Gestational versus genetic mothers. PMID- 1614489 TI - Gestational versus genetic mothers. PMID- 1614490 TI - Neutrons give improved results in selected tumour types. PMID- 1614491 TI - Which headache? Migraine: a start in a series on some of the most common headache conditions. PMID- 1614492 TI - Drug interactions involving antibiotics. PMID- 1614493 TI - Primary care obstetrics in South Africa. PMID- 1614494 TI - Setting priorities in nursing research. PMID- 1614495 TI - Can simulation replace practica? PMID- 1614496 TI - Systemic and other factors that affect wound healing. PMID- 1614497 TI - Leeds disunited. PMID- 1614498 TI - US company's gene therapy trial is first to bypass RAC for approval. PMID- 1614499 TI - House vote to kill SSC reflects squeeze that budget deficit puts on all research. PMID- 1614500 TI - Japan 'finds' money for research. PMID- 1614501 TI - Clinical research damaged by UK health service reforms. PMID- 1614502 TI - FBI attaches strings to its DNA database. PMID- 1614503 TI - Lab death blamed on gas build-up. PMID- 1614504 TI - Large, oil-soaked endowment helps state universities weather current hard times. PMID- 1614505 TI - Biotechnology leads the way as state moves beyond ground-based economy. PMID- 1614506 TI - SW medical center, famous and favoured, is thriving. PMID- 1614507 TI - Houston breeds biotechnology hot shots. PMID- 1614508 TI - New biotechnology institute at Rice promotes interdisciplinary studies. PMID- 1614509 TI - San Antonio fills research park by making offers that scientists cannot refuse. PMID- 1614510 TI - Texas A&M struggles to gain the respect that its researchers have already won. PMID- 1614511 TI - Space science in Texas means basic research as well as support for manned flights. PMID- 1614512 TI - San Antonio aims for spot on high-technology map. PMID- 1614513 TI - Malaria. Asexual deviants take over. PMID- 1614514 TI - Rhizobium--plant signal exchange. AB - Initial stages in the Rhizobium-legume symbiosis can be thought of as a reciprocal molecular conversation: transmission of a gene inducer from legume host to bacterium, with ensuing bacterial synthesis of a morphogen that is transmitted to the plant, switching the developmental fate of the legume root. These signal molecules have a key role in determining bacterium-host specificity and the purified Nod factor compounds provide useful new tools to probe plant cell function. PMID- 1614515 TI - Rapid switching to multiple antigenic and adhesive phenotypes in malaria. AB - Adhesion of parasitized erythrocytes to post-capillary venular endothelium or uninfected red cells is strongly implicated in the pathogenesis of severe Plasmodium falciparum malaria. Neoantigens at the infected red-cell surface adhere to a variety of host receptors, demonstrate serological diversity in field isolates and may also be a target of the host-protective immune response. Here we use sequential cloning of P. falciparum by micromanipulation to investigate the ability of a parasite to switch antigenic and cytoadherence phenotypes. Our data show that antigens at the parasitized cell surface undergo clonal variation in vitro in the absence of immune pressure at the rate of 2% per generation with concomitant modulations of the adhesive phenotype. A clone has the potential to switch at high frequency to a variety of antigenic and adhesive phenotypes, including a new type of cytoadherence behaviour, 'auto-agglutination' of infected erythrocytes. This rapid appearance of antigenic and functional heterogeneity has important implications for pathogenesis and acquired immunity. PMID- 1614516 TI - Alterations in a yeast protein resembling HIV Tat-binding protein relieve requirement for an acidic activation domain in GAL4. AB - The acidic transcriptional activation motif functions in all eukaryotes, which suggests that it makes contact with some universal component of the transcriptional apparatus. Transcriptional activation by the yeast regulatory protein GAL4 requires an acidic region at its carboxyl terminus. Here we implement a selection scheme to determine whether GAL4 can still function when this C-terminal domain has been deleted. It can, when accompanied by a mutation in the SUG1 gene which is an essential gene in yeast. Analysis of mutant SUG1 in combination with various alleles of GAL4 indicates that SUG1 acts through a transcriptional pathway that depends on GAL4, but requires a region of GAL4 other than the C-terminal acidic activation domain. The predicted amino-acid sequence of SUG1 closely resembles that of two human proteins, TBP1 and MSS1, which modulate expression mediated by the human immunodeficiency virus tat gene. PMID- 1614517 TI - Processing pathways for presentation of cytosolic antigen to MHC class II restricted T cells. AB - Antigens presented to CD4+ T cells derive primarily from exogenous proteins that are processed into peptides capable of binding to class II major histocompatibility complex (MHC) molecules in an endocytic compartment. In contrast, antigens presented to CD8+ T cells derive mostly from proteins processed in the cytosol, and peptide loading onto class I MHC molecules in an early exocytic compartment is dependent on a transporter for antigen presentation encoded in the class II MHC region. Endogenous cytosolic antigen can also be presented by class II molecules. Here we show that, unlike class I-restricted recognition of antigen, HLA-DR1-restricted recognition of cytosolic antigen occurs in mutant cells without a transporter for antigen presentation. In contrast, DR1-restricted recognition of a short cytosolic peptide is dependent on such a transporter. Thus helper T-cell epitopes can be generated from cytosolic antigens by several mechanisms, one of which is distinct from the classical class I pathway. PMID- 1614518 TI - Too many trinucleotide repeats. PMID- 1614519 TI - Human insulin. PMID- 1614520 TI - Why cheat? PMID- 1614521 TI - Media make AIDS wishes come true. PMID- 1614522 TI - Cancer. p53, guardian of the genome. PMID- 1614523 TI - Let the French sue. PMID- 1614524 TI - Immunology. A sense of something missing. PMID- 1614525 TI - Blood substitutes and infection. PMID- 1614526 TI - Robert Gallo forced off NIH stage after HHS vetoes public briefing. PMID- 1614527 TI - Quantification of the disorder in network-modified silicate glasses. AB - Local order in silicate glasses has been observed by many experimental techniques to be similar to that in crystalline materials. Details of the intermediate-range order are more elusive, but essential for understanding the lack of long-range symmetry in glasses and the effect of composition on glass structure. Two dimensional 17O dynamic-angle-spinning nuclear magnetic resonance experiments reveal intermediate-range order in the distribution of inter-tetrahedral (Si-O Si) bond angles and a high degree of order in the disposition of oxygen atoms around the network-modifying cations. PMID- 1614528 TI - Group asks NIH to stop growth hormone trials. PMID- 1614529 TI - NIH makes room for the unconventional after Congress mandates new programme. PMID- 1614530 TI - Panel trims NSF budget. PMID- 1614531 TI - French AIDS scandal goes to court. PMID- 1614532 TI - Japan moves gingerly towards guidelines on gene therapy. PMID- 1614533 TI - MHC class I alloantigen specificity of Ly-49+ IL-2-activated natural killer cells. AB - The molecular basis of target cell recognition by CD3- natural killer (NK) cells is poorly understood, despite the ability of NK cells to lyse specific tumour cells. In general, target cell major histocompatibility complex (MHC) class I antigen expression correlates with resistance to NK cell-mediated lysis, possibly because NK cell-surface molecules engage MHC class I antigens and consequently deliver inhibitory signals. Natural killer cell allospecificity involves the MHC class I peptide-binding cleft, and further understanding of this allospecificity should provide insight into the molecular mechanisms of NK cell recognition. The Ly-49 cell surface molecular mechanisms of NK cell recognition. The Ly-49 cell surface molecule is expressed by 20% of CD3- NK cells in C57BL/6 mice (H-2b). Here we show that C57BL/6-derived, interleukin-2-activated NK cells expressing Ly 49 do not lyse target cells displaying H-2d or H-2k despite efficient spontaneous lysis by Ly-49- effector cells. This preferential resistance correlates with expression of target cell MHC class I antigens. Transfection and expression of H 2Dd, but not H-2Kd or H-2Ld, renders a susceptible target (H-2b) resistant to Ly 49+ effector cells. The transfected resistance is abrogated by monoclonal antibodies directed against Ly-49 or the alpha 1/alpha 2 domains of H-2Dd, suggesting that Ly-49 specifically interacts with the peptide-binding domains of the MHC class I alloantigen, H-2Dd. Inasmuch as Ly-49+ effector cells cannot be stimulated to lyse H-2Dd targets, our results indicate that NK cells may possess inhibitory receptors that specifically recognize MHC class I antigens. PMID- 1614534 TI - Ban on primate trade seen as threat to animals. PMID- 1614535 TI - Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase. AB - The macrolide rapamycin induces cell cycle G1 arrest in yeast and in mammalian cells, which suggests that an evolutionarily conserved, rapamycin-sensitive pathway may regulate entry into S phase. In mammals, rapamycin inhibits interleukin-2 receptor-induced S phase entry and subsequent T-cell proliferation, resulting in immunosuppression. Here we show that interleukin-2 selectively stimulates the phosphorylation and activation of p70 S6 kinase but not the erk encoded MAP kinases and rsk-encoded S6 kinases. Rapamycin completely and rapidly inhibits interleukin-2-induced phosphorylation and activation of p70 S6 kinase at concentrations comparable to those blocking S phase entry of T cells (0.05-0.2 nM). The structurally related macrolide FK506 competitively antagonizes the actions of rapamycin, indicating that these effects are mediated by FKBP, which binds the transition-state mimic structure common to both rapamycin and FK506 (refs 4, 6, 9-11). The selective blockade of the p70 S6 kinase activation cascade by the rapamycin-FKBP complex implicates this signalling pathway in the regulation of T cell entry into S phase. PMID- 1614536 TI - Antibody and HIV-1 gp120 recognition of CD4 undermines the concept of mimicry between antibodies and receptors. AB - It has been proposed that antibodies can mimic the binding of a receptor to its ligand and that anti-idiotype antibodies raised against such antibodies can be used to identify the receptor. A large number of antibodies have been raised against CD4, the receptor on T cells for the envelope glycoprotein gp120 of the human immunodeficiency virus, and the site at which gp120 binds to CD4 has been delineated. It has therefore become possible to contrast the fine specificities of a natural ligand (gp120) and antibodies that interact with the receptor at the same site. Here we report that out of a panel of 225 anti-CD4 antibodies, only one showed fine binding specificity that was broadly like that of gp120, but the evidence was against this being an exact mimic. Thus the data indicate that the production of antibody mimics will occur very rarely or not at all and that the anti-idiotype approach is unlikely to be useful. This contention is supported by a review of the results of attempts to use this approach. Taking strict criteria for success, there is no example for which the anti-idiotype approach has led to the discovery of a previously undescribed receptor or other protein of interest. PMID- 1614537 TI - Amplification of a gene encoding a p53-associated protein in human sarcomas. AB - Despite extensive data linking mutations in the p53 gene to human tumorigenesis, little is known about the cellular regulators and mediators of p53 function. MDM2 is a strong candidate for one such cellular protein; the MDM2 gene was originally identified by virtue of its amplification in a spontaneously transformed derivative of mouse BALB/c cells and the MDM2 protein subsequently shown to bind to p53 in rat cells transfected with p53 genes. To determine whether MDM2 plays a role in human cancer, we have cloned the human MDM2 gene. Here we show that recombinant-derived human MDM2 protein binds human p53 in vitro, and we use MDM2 clones to localize the human MDM2 gene to chromosome 12q13-14. Because this chromosomal position appears to be altered in many sarcomas, we looked for changes in human MDM2 in such cancers. The gene was amplified in over a third of 47 sarcomas, including common bone and soft tissue forms. These results are consistent with the hypothesis that MDM2 binds to p53, and that amplification of MDM2 in sarcomas leads to escape from p53-regulated growth control. This mechanism of tumorigenesis parallels that for virally-induced tumours, in which viral oncogene products bind to and functionally inactivate p53. PMID- 1614538 TI - Wild-type p53 activates transcription in vitro. AB - The p53 protein is an important determinant in human cancer and regulates the growth of cells in culture. It is known to be a sequence-specific DNA-binding protein with a powerful activation domain, but it has not been established whether it regulates transcription directly. Here we show that intact purified wild-type human and murine p53 proteins strongly activate transcription in vitro. This activation depends on the ability of p53 to bind to a template bearing a p53 binding sequence. By contrast, tumour-derived mutant p53 proteins cannot activate transcription from the template at all, and when complexed to wild-type p53, these mutants block transcriptional activation by the wild-type protein. Moreover, the simian virus 40 large T antigen inhibits wild-type p53 from activating transcription. Our results support a model in which p53 directly activates transcription but this activity can be inhibited by mutant p53 and SV40 large T antigen through interaction with wild-type p53. PMID- 1614539 TI - A new approach to protein fold recognition. AB - The prediction of protein tertiary structure from sequence using molecular energy calculations has not yet been successful; an alternative strategy of recognizing known motifs or folds in sequences looks more promising. We present here a new approach to fold recognition, whereby sequences are fitted directly onto the backbone coordinates of known protein structures. Our method for protein fold recognition involves automatic modelling of protein structures using a given sequence, and is based on the frameworks of known protein folds. The plausibility of each model, and hence the degree of compatibility between the sequence and the proposed structure, is evaluated by means of a set of empirical potentials derived from proteins of known structure. The novel aspect of our approach is that the matching of sequences to backbone coordinates is performed in full three dimensional space, incorporating specific pair interactions explicitly. PMID- 1614540 TI - Head of drug company takes Serbian post. PMID- 1614541 TI - Long-range correlations within DNA. PMID- 1614542 TI - Molecular biology. Chlamydomonas surrenders. PMID- 1614543 TI - Dopamine receptors. Which D4 do you have? PMID- 1614544 TI - Vertebrate development. Induction and all that. PMID- 1614545 TI - Proto-vav and gene expression. PMID- 1614546 TI - Queen activation of lazy workers in colonies of the eusocial naked mole-rat. AB - Evolutionary conflicts of interest are expected to arise in genetically diverse social groups. In eusocial insect societies, a potential conflict exists between the queen and her workers over how active the workers should be, and evidence exists that queen aggression increases activity levels of her lazier workers. Here I provide evidence that queen aggression (shoving) in laboratory colonies of the eusocial mammal, the naked mole-rat (Heterocephalus glaber), is a convergently evolved manifestation of queen-worker conflict over worker activity. Queen-initiated shoves activate inherently lazy workers, which tend to be larger and/or less related to the queen than are infrequently shoved, industrious workers. In addition, queen removal selectively depresses the activity of workers that are larger and less related to her. Finally, queen shoving and worker inactivity are pronounced when colonies are satiated but not when colonies are hungry, indicating that the underlying 'work-conflict' is highly context specific. PMID- 1614547 TI - Objective analysis of the topological organization of the primate cortical visual system. AB - The primate cortical visual system is composed of many structurally and functionally distinct areas, each receiving and sending about 10 projections from and to other cortical areas. The visual cortex is thus served by many cortico cortical connections to form a network of considerable complexity. Thus the gross organization of this cortical processing system presents a formidable topological problem: although the spatial position of the areas in the brain is reasonably well established, the gross 'processing architecture' defined by the connections, is less well understood. Here I report an optimization approach that gives both qualitative and quantitative insight into the connectional topology of the primate cortical visual system. This approach supports suggestions that the system is divided into a dorsal 'stream' and a ventral 'stream' with limited cross-talk, that these two streams reconverge in the region of the principal sulcus (area 46) and in the superior temporal polysensory areas, that the system is hierarchically organized, and that the majority of the connections are from 'nearest-neighbour' and 'next-door-but-one' areas. PMID- 1614548 TI - Shigella flexneri induces apoptosis in infected macrophages. AB - The Gram-negative bacterial pathogen Shigella flexneri causes dysentery by invading the human colonic mucosa. Bacteria are phagocytosed by enterocytes, escape from the phagosome into the cytoplasm and spread to adjacent cells. After crossing the epithelium, Shigella reaches the lamina propria of intestinal villi, the first line of defence. This tissue is densely populated with phagocytes that are killed in great numbers, resulting in abscesses. The genes required for cell invasion and macrophage killing are located on a 220-kilobase plasmid. We report here on the mechanism of cytotoxicity used by S. flexneri to kill macrophages. Each of four different strains was tested for its capacity to induce cell death. An invasive strain induced programmed cell death (apoptosis), whereas its non invasive, plasmidcured isogenic strain was not toxic; neither was a mutant in ipa B (ref. 10) (invasion protein antigen), a gene necessary for entry. A non invasive strain expressing the haemolysin operon of Escherichia coli induced accidental cell death (necrosis), demonstrating that other bacterial cytotoxic mechanisms do not lead to apoptosis. This is the first evidence that an invasive bacterial pathogen can induce suicide in its host cells. PMID- 1614550 TI - US muddles policy on fetal tissue. PMID- 1614549 TI - Hsp90 chaperones protein folding in vitro. AB - The heat-shock protein Hsp90 is the most abundant constitutively expressed stress protein in the cytosol of eukaryotic cells, where it participates in the maturation of other proteins, modulation of protein activity in the case of hormone-free steroid receptors, and intracellular transport of some newly synthesized kinases. A feature of all these processes could be their dependence on the formation of protein structure. If Hsp90 is a molecular chaperone involved in maintaining a certain subset of cellular proteins in an inactive form, it should also be able to recognize and bind non-native proteins, thereby influencing their folding to the native state. Here we investigate whether Hsp90 can influence protein folding in vitro and show that Hsp90 suppresses the formation of protein aggregates by binding to the target proteins at a stoichiometry of one Hsp90 dimer to one or two substrate molecule(s). Furthermore, the yield of correctly folded and functional protein is increased significantly. The action of Hsp90 does not depend on the presence of nucleoside triphosphates, so it may be that Hsp90 uses a novel molecular mechanism to assist protein folding in vivo. PMID- 1614551 TI - Controversial NIH genome researcher leaves for new $70-million institute. PMID- 1614553 TI - Genentech's stance on biodiversity riles staff. PMID- 1614552 TI - Search for contaminant in EMS outbreak goes slowly. PMID- 1614554 TI - Delays, confusion over rules hinder EC research projects. PMID- 1614555 TI - Solving the U.S. health care dilemma. PMID- 1614556 TI - Solving the U.S. health care dilemma. PMID- 1614557 TI - Chronic fatigue syndrome. A practical approach. PMID- 1614559 TI - Providing services in nursing homes. A physician's legal obligations. PMID- 1614558 TI - Status epilepticus. Latest approaches in management. AB - Status epilepticus--convulsive or non-convulsive--is a major neurological emergency. Vital neurons are lost with every moment of delay. Every physician should approach status epilepticus in a manner analogous to cardiopulmonary arrest: a structured series of interventions following a defined protocol to produce better results than a haphazard approach. In both situations, speedy intervention is essential to prevent irreversible damage. PMID- 1614560 TI - Geriatric peer-counseling. Pilot project provides support for the homebound elderly. PMID- 1614561 TI - Elegy for a way of life. A physician laments the changes in American medicine; with comment from deans at the state's four medical schools. PMID- 1614562 TI - Alexander Fleming and penicillin. The chance of a lifetime? PMID- 1614563 TI - [An overlooked lymphoma of the stomach can sometimes have serious consequences]. PMID- 1614564 TI - [Prevention and treatment of osteoporosis]. AB - Despite the fact that osteoporosis is a common disease and an important cause of morbidity and mortality, that screening tests are available which are safe and acceptable to patients, and that effective therapy is possible, osteoporosis remains a controversial subject. The Dutch Health Advisory Board (Gezondheidsraad) recently submitted to the Ministry of Health a balanced and comprehensive report to remedy this controversial situation. As often in a consensus report made by a variety of experts, completeness is assured but the necessary relevance of the statements and the feasibility of the therapeutic recommendations are not always clear. Based on personal experience, clinical practice and research in osteoporosis, the author formulates a number of messages which complement the report. The following messages are elaborated: osteoporosis is a silent thief; backache during the menopause is not always osteoporosis; detection of the patient at risk for osteoporotic fractures is possible; primary osteoarthrosis protects against osteoporosis; bone densitometry has given osteoporosis a scientific cachet; bones are not stones, effective prevention and treatment are possible, there are alternatives to calcium and hormone replacement therapies. There is still much to learn about osteoporosis and its treatment. Nevertheless, there is a great deal that is known and we need to give the best advice we can in the light of this knowledge. PMID- 1614565 TI - [Bone densitometry and osteoporosis]. PMID- 1614566 TI - [Postmenopausal estrogen substitution and the risk of atherosclerotic heart and vascular diseases]. PMID- 1614567 TI - [Non-Hodgkin lymphoma of the stomach as an entity. Concept formation and current developments]. PMID- 1614568 TI - [Revision consensus osteoporosis]. AB - Several years ago a consensus guideline conference was organised both in the United States (1984) and in the Netherlands (1985) on case finding, prevention and treatment of osteoporosis. The most important conclusion of both conferences was that oestrogen substitution can significantly reduce the incidence of fractures in postmenopausal women. This statement has not changed in the revised guidelines on osteoporosis of 1991. As far as the effect of hormonal substitution of oestrogens with or without progestagens in relation to cardiovascular disease and breast and endometrial carcinoma is concerned, insights have hardly changed in the last 5 years. The value of other drugs in the treatment of osteoporosis, however, has become better known. Both diphosphonates and anabolic steroids have recently made a comeback. PMID- 1614569 TI - [Good 10-year results following cemented total knee arthroplasty]. AB - The results of primary total knee arthroplasty in patients with a follow-up of 4 10 years are presented. The study population consisted of osteoarthritis as well as rheumatoid arthritis patients. Both groups were analyzed separately for postoperative pain reduction at rest and during activity, as well as for improvement of some daily activities (walking distance, stair climbing). Pain reduction at rest and during activity was maintained during the follow-up period of 4-10 years. The walking distance and the ability to climb stairs improved during the first few postoperative years, but declined in the later postoperative years. Survival curve analysis of the total knee arthroplasty showed good results for osteoarthritis as well as rheumatoid arthritis (estimated probability of survival of the prosthesis at 10 years' follow-up was 94%). PMID- 1614570 TI - [Rhabdomyolysis, disseminated intravascular coagulation and multiple organ failure in a patient with cocaine and heroine poisoning]. AB - A 19-year-old female patient with cocaine and heroin intoxication is described in whom several life threatening complications such as hypovolemic shock, cardiopulmonary insufficiency, rhabdomyolysis, diffuse intravascular coagulation and multiple organ failure occurred. The patient survived the intoxication after quick intensive treatment. PMID- 1614571 TI - [The patient's question: important determinant for quality of medical actions]. PMID- 1614572 TI - [Dry-bed training and nocturnal enuresis]. PMID- 1614573 TI - [Diagnostic management in suspected pulmonary embolism: results of a survey among Dutch internists and pulmonologists]. PMID- 1614574 TI - [Insulinoma and octreotide]. PMID- 1614575 TI - [Neuropathic pain; causes and treatment]. PMID- 1614576 TI - AIDS & the physician. PMID- 1614577 TI - Comments on functional endoscopic sinus surgery. AB - A brief comment on functional endoscopic sinus surgery with the result of 208 cases were presented. It was stressed that all sinus patients must have very intensive conservative management, much longer than previously thought, before functional endoscopic sinus surgery should be employed. Functional endoscopic sinus surgery is a vastly superior method of surgically treating the paranasal sinuses. It is based on the principles of reestablishing normal physiology of the sinus mucosa. It affords an excellent basis for removal of disease, establishing natural drainage, aeration and restoration of normal physiology. PMID- 1614578 TI - The practice of medicine in Nebraska prior to statehood. PMID- 1614579 TI - "Autonomy and the art of medicine". PMID- 1614580 TI - Exposures during pregnancy and lactation. PMID- 1614581 TI - The role of stereotactic biopsy in the management of HIV-related focal brain lesions. AB - The criteria for brain biopsy in patients with acquired immunodeficiency syndrome (AIDS) remain unclear and without universal acceptance. In order to shed more light on this issue, the authors reviewed the records of 25 AIDS patients with focal cerebral lesions who consecutively underwent stereotactic biopsy between November 1988 and October 1990. The most frequently occurring diagnoses were lymphoma (36%), progressive multifocal leukoencephalopathy (24%), and toxoplasmosis (8%). Patients whose central nervous system disease resulted in their initial presentation (approximately 40%) survived a median of 37 weeks, as opposed to 6 weeks for those who had previous AIDS-related infections. The proportion of biopsies of contrast-enhancing lesions that were diagnostic and thereby contributed to the patients' therapeutic management was 87.5%. On the other hand, only 67% of the biopsies of nonenhancing lesions were diagnostic, and none of these lesions were treatable. All of the lymphoma patients had had AIDS for some time and, despite a reasonable preoperative Karnofsky score and postoperative radiation therapy, their median survival was only 6 weeks; however, biopsy was critical to their therapeutic management. Early brain biopsy, rather than empiric antitoxoplasmosis therapy, appears indicated for aggressive therapy of contrast-enhancing lesions in patients who have had previous manifestations of AIDS. The role for biopsy of nonenhancing lesions is less clear, but it may provide prognostic information. PMID- 1614582 TI - Postoperative low-dose heparin decreases thromboembolic complications in neurosurgical patients. AB - Thromboembolic complications are a major cause of postoperative morbidity and mortality in the neurosurgical patient. Prophylaxis with lower extremity pneumatic compression boots (PCBs) reduces the incidence of lower extremity deep vein thrombosis (DVT) but has not been shown to affect the incidence of pulmonary embolism (PE). Prophylaxis with low-dose heparin has consistently reduced the incidence of both DVT and PE in studies on general surgical patients but has not been adopted for use in neurosurgery primarily for fear of causing catastrophic hemorrhage. We report on a series of 138 consecutive adult patients who underwent major neurosurgical procedures on a general neurosurgical service at our institution. Patients were treated with intraoperative PCBs and, starting on the morning of the first postoperative day, with a regimen of 5000 U of heparin administered subcutaneously twice daily. This treatment was continued until patients were fully ambulatory. PCBs were discontinued 24 hours after the first administration of heparin. None of the heparin-treated patients suffered postoperative hemorrhage. We compared this series with a control group of 473 adult patients who had previously undergone major neurosurgical procedures on the same neurosurgical service. These patients had been treated with intraoperative and postoperative PCBs alone. The control group had a 3.2% incidence of thromboembolic complications (15 of 473; eight DVT, seven PE). Prophylaxis with PCBs plus heparin significantly (P = 0.020) reduced the incidence of thromboembolic complications: no PCBs/heparin-treated patient exhibited clinical evidence of PE or DVT (0%, 0/138). We conclude that a combination of intraoperative PCBs and postoperative low-dose heparin is a safe and effective method by which to reduce thromboembolic complications in the neurosurgical patient. PMID- 1614583 TI - Essential hypertension associated with neurovascular compression: angiographic findings. AB - According to the hypothesis of Jannetta, an arterial compression of the left root entry zone (REZ) of cranial nerves IX and X by looping arteries could play an important role in the pathogenesis of essential hypertension. In an initial anatomical study, the positions of the left vagus and glossopharyngeal nerves in the skull were radiographically determined in 10 cadavers. By using a pattern of REZ topography developed from this information, the angiographic findings in 107 hypertensive and 100 normotensive patients were then compared retrospectively. In 80% of the angiograms of the hypertensive patients that could be evaluated, an artery crossed the left REZ of cranial nerves IX and X. Most frequently, this was the posterior inferior cerebellar artery (35.3% of cases), followed by the vertebral artery (29.4% of cases) and the anterior inferior artery (19.1% of cases). In 9 cases (13%), both the posterior inferior cerebellar artery and the vertebral artery appeared in the REZ. Frequently, a larger diameter of the left vertebral artery was found. The angiograms of normotensive patients that could be evaluated revealed an artery in the REZ in only 34.5% of cases. Our results support the hypothesis that essential hypertension may be associated with neurovascular compression of the left REZ of cranial nerves IX and X. PMID- 1614584 TI - Computerized electroencephalographic monitoring and selective shunting: influence on intraoperative administration of phenylephrine and myocardial infarction after general anesthesia for carotid endarterectomy. AB - During carotid endarterectomy (CEA), phenylephrine infusions are commonly used to induce hypertension during carotid clamping in an attempt to increase collateral cerebral blood flow and prevent cerebral ischemia. Although this practice appears to increase the incidence of intraoperative myocardial ischemia during CEA when general anesthesia is employed, whether the limited use of phenylephrine infusions in specific instances of cerebral ischemia, as shown on an electro encephalogram, results in low perioperative rates of both myocardial infarction (MI) and cerebral infarction remains unclear. We studied 171 CEAs done under general anesthesia performed with selective shunting based on the identification of cerebral ischemia by a two-channel computerized electroencephalographic monitor. The use of a phenylephrine infusion was restricted to the following instances of cerebral ischemia: 1) ischemia associated with hypotension that did not resolve within 2 minutes of decreases in anesthetic administration and treatment with fluid and/or colloid; 2) ischemia poorly or slowly responsive to shunt placement, accompanied by either hypo- or normotension; and 3) ischemia poorly or slowly responsive to removal of the carotid clamp, accompanied by either hypo- or normotension. Two non-Q wave MIs (1.2%) occurred, both nonfatal. There were two cerebral infarctions (1.2%) and three deaths not related to MI (1.8%). Based on these findings, in order to decrease the incidence of both MI and cerebral infarction after general anesthesia for CEA, we recommend the restrictive use of phenylephrine-induced hypertension for specific instances of slowly or poorly reversible cerebral ischemia, as shown on the electroencephalogram. PMID- 1614585 TI - Preoperative risks predict neurological outcome of carotid endarterectomy related stroke. AB - The aim of this study was to determine if preoperative risk factors are predictors of poor stroke outcome after carotid endarterectomy. In addition, the effect of other stroke risk factors on stroke severity was determined. A retrospective review of carotid endarterectomy results spanning 10 years, encompassing 561 patients, and reporting the combined results of all surgeons at our institution was performed. Patients were assigned to one of four groups. There were 227 patients with no preoperative risks (Group 1), 61 with angiographic risks (Group 2), 196 with medical risks with or without angiographic risks (Group 3), and 77 with neurological risks with or without medical/angiographic risks (Group 4). Other risks associated with stroke occurrence were recorded including: intraoperative risks (cross-clamp time, use of shunt, use of glucose solutions), surgical complications (carotid occlusion/thrombus or ligation), and medical complications (hypoxia, myocardial infarct). Stroke incidence was 5% with 2% (11 patients) and 3.4% (19 patients) having good and poor outcomes, respectively. Stroke incidence was highest in Groups 2 and 4 (10 and 14%, respectively), and Group 4 had the highest incidence of poor-outcome stroke (12%). Cross-clamp time, intraoperative shunt placement, and intraoperative glucose administration were similar among preoperative risk groups and were not primary determinants of stroke severity. The most common medical complication was myocardial infarction, which had the highest incidence in Groups 3 and 4 (6.1 and 5%, respectively). The highest incidence of surgical complications occurred in Groups 2 and 4, carotid thrombosis being the most common event (16 patients). Surgical complications were more commonly associated with stroke than were medical complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614586 TI - Differentiation of pituitary adenoma and meningioma: visualization with positron emission tomography and [11C]-L-deprenyl. AB - Seven patients with clinically nonsecreting pituitary adenoma and 5 patients with meningioma were examined with positron emission tomography using [11C]-LL deprenyl and [11C]-LL-methionine. The dynamics of the uptake of [11C]-L-deprenyl in the pituitary adenomas demonstrated a rapid and high uptake immediately after the injection, and, later, an almost constant level was observed that was equal to or higher than that observed in normal brain tissue. In the meningiomas, however, the initially high uptake was followed by a marked decrease with time, reaching a level that was approximately half that observed in brain tissue. The study demonstrated high binding of [11C]-L-deprenyl to monoamine oxidase B in pituitary adenomas, whereas the binding in meningiomas was very low. This fact can be used in the differential diagnosis of pituitary adenoma and parasellar meningioma. Operative samples from 10 patients with meningioma and from 5 patients with pituitary adenoma were analyzed biochemically for activity of monoamine oxidase B, using [14C]-phenyl-ethylamine as substrate. The nonsecreting pituitary adenomas demonstrated high enzyme activity, the secreting adenomas about one-tenth of that of the nonsecreting, and the meningiomas one-thirtieth of that of nonsecreting adenomas. PMID- 1614587 TI - Outcome analysis in 654 surgically treated lumbar disc herniations. AB - This article reports the outcomes of 654 consecutive patients treated during a 4.5-year period. Patients had a microdiscectomy, a laminectomy plus microdiscectomy, or a decompressive laminectomy with a microdiscectomy. The causes of ruptured discs were lifting (31.4%), falls (10.2%), and sports (10.0%). Almost all patients had complained of leg pain (99%), and 79% had radicular pain in a dermatomal distribution. Thirty-three percent of the patients had been involved in industrial accidents, and 6% had legal claims pending during the surgical period. Almost 11% of the patients had complications, and there was one death caused by abdominal arterial bleeding. Patients were also rated according to the Prolo Functional-Economic Outcome Rating Scale to improve the ability to compare series in the future. Almost 80% of the patients had good outcomes as defined by scores on this scale of 8 (16.2%), 9 (33.2%), and 10 (26.9%). Several conclusions can be drawn from the results of this series: 1) most patients had good outcomes; 2) patients with nonindustrial injuries had better outcomes than did patients with industrial injuries; 3) professionals with legal concerns and laborers with industrial insurance had good outcomes; and 4) the Functional Economic Outcome Rating Scale appears to be a useful tool for comparing different procedures more objectively and for comparing the outcomes across series. PMID- 1614588 TI - The subarachnoid spaces in craniosynostosis. AB - A review of 85 patients with various forms of craniosynostosis showed predictable patterns of dilatation of the subarachnoid spaces in regions of compensatory skull growth. The characteristic pattern in sagittal synostosis (43 patients) included dilatation of the frontal and occipital subarachnoid spaces associated with the elongation of the anteroposterior dimension of the skull and widening of the interhemispheric fissure. In 11 patients with unilateral coronal synostosis, dilatations of the subarachnoid spaces over the contralateral frontal lobe, the sylvian regions, and the ipsilateral temporal lobe tip were consistent with the skull changes of contralateral frontal bossing, increased bitemporal dimension, and elevation of the sphenoid wing, respectively. Four patients with bilateral coronal synostosis also had enlarged subarachnoid spaces high over the convexities of the brain consistent with the towering configuration of the skull. Four patients with true lambdoid synostosis had dilatation of the subarachnoid space only over the ipsilateral frontal lobe associated with compensatory bossing of the frontal bone. Ten of 14 patients with lambdoid deformities had bilateral enlargement of the subarachnoid spaces suggesting brain atrophy and an underlying motor delay accounting for the position-induced skull changes. The findings suggest that focal hydrodynamic mechanisms are involved in the compensatory skull changes seen in craniosynostosis. PMID- 1614589 TI - Failure of conventionally fractionated radiotherapy to decrease the risk of hemorrhage in inoperable arteriovenous malformations. AB - Twenty-six patients with arteriovenous malformations (AVMs) were treated between 1965 and 1986 with conventional fractionated radiotherapy at the Royal Marsden Hospital. There were 14 male patients and 12 female, aged 11 to 57 years (median, 24 yr). Twenty-five patients completed radiotherapy with a localized treatment target volume of a dose of 40 to 54 Gy. The median follow-up was 14.5 years. Eleven patients had an additional hemorrhage. The actuarial annual risk of bleeding was 2.3%, which is similar to that found in untreated patients. Follow up angiograms were performed in 11 patients, and 10 showed persistence of AVM. The results suggest that fractionated radiotherapy in conventional doses does not make a large impact on the risk of hemorrhage in patients with inoperable AVMs, and, where possible, stereotactic external beam radiotherapy/radiosurgery should be employed. PMID- 1614590 TI - Single intracisternal bolus of recombinant tissue plasminogen activator in patients with aneurysmal subarachnoid hemorrhage: preliminary assessment of efficacy and safety in an open clinical study. AB - Intracisternal thrombolysis with recombinant tissue plasminogen activator (rtPA) was performed in 20 patients with aneurysmal subarachnoid hemorrhage. All patients had blood accumulations in the basal cisterns according to Fisher's Grade III, thus being at a high risk for the development of posthemorrhagic delayed ischemic deficits (DID). All patients underwent an operation within 72 hours after aneurysm rupture. After the aneurysm had been excluded from the cerebral circulation, a single bolus of 10 mg of rtPA was injected into the basal cisterns. Postoperatively, serial computed tomographic examinations demonstrated radical blood clot removal in all patients. Daily transcranial Doppler examinations revealed accelerated blood flow velocities in 16 of 20 patients. The postoperative results according to the Glasgow Outcome Scale were as follows: 16 patients were Grades I and II, 2 patients were Grade III. Two patients died postoperatively, 1 because of a bowel perforation, and 1 from DID attributable to the development of a cerebral vasospasm. No postoperative bleeding complications occurred. It is concluded that pharmacological removal of subarachnoid blood accumulations can be achieved in a safe and effective way by an intrathecal single bolus of 10 mg of rtPA instilled into the basal cisterns after aneurysm clipping. The acceleration of blood flow velocities in a number of patients indicated that posthemorrhagic arterial narrowing was not completely prevented by this treatment, but this remained asymptomatic in 19 of 20 patients. Although extensive blood clot removal can be achieved by a single bolus of rtPA, more radical or complete blood removal probably requires the use of higher drug concentrations or additional postoperative intracisternal or intraventricular rtPA injections, for which further studies are needed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614591 TI - Blood-brain barrier permeability changes after experimental subarachnoid hemorrhage. AB - Basic mechanisms underlying cerebrovascular permeability responses to subarachnoid hemorrhage (SAH) are still to be defined in detail. Previous investigations examining the occurrence of blood-brain barrier (BBB) breakdown after SAH in the experimental setting have yielded conflicting results. In a rat model of SAH, we assessed BBB changes by means of the quantitative [14C]-alpha aminoisobutyric acid technique. Experiments were carried out on the second day post-SAH. In blood-injected rats [14C]-alpha-aminoisobutyric acid transport across the BBB increased significantly in cerebral cortices and cerebellar gray matter, averaging 1.3 to 1.5 times control values. The present data indicate that SAH induces well-defined changes in BBB function, possibly involved in the pathogenesis of post-SAH cerebral dysfunction in humans. Results reported here have also potential clinical implications for the management of aneurysm patients. PMID- 1614592 TI - Transient elevation of the intracranial pressure increases the infarct size and perifocal edema after subsequent middle cerebral artery occlusion in the rat. AB - The objective of this study was to mimic in a simple experiment the two major brain insults sustained by the patient with a subarachnoid hemorrhage, that is, the ictus and the subsequent delayed reduction of focal cerebral blood flow caused by vasospasm without the interference of subarachnoid blood, to test the hypothesis that ictal events not related to the presence of blood in the subarachnoid space per se may be important for the development of ischemic deficits and cerebral infarction when vasospasm develops. Groups of rats were subjected to a sudden transient elevation of the intracranial pressure to a level causing a brief period of complete global ischemia by infusion of mock cerebrospinal fluid into the cisterna magna (this manipulation was designed to allow survival of the animal and recovery of consciousness). Two and one-half hours later, a focal ischemic insult was induced by occlusion of the middle cerebral artery. Rats subjected to middle cerebral artery occlusion alone and sham operation served as controls. The infarct size was used as the end point and was calculated on brain slices stained with 2,3,5-triphenyltetrazolium chloride. The study demonstrates that a brief sudden elevation in intracranial pressure, in itself consistent with survival and recovery, increased the vulnerability of the brain to a subsequent focal ischemic insult. Thus the combination of insults resulted in significantly (P less than 0.05) larger infarcts than did middle cerebral artery occlusion alone. Further, this combination of insults resulted in a disproportionate enlargement of the affected hemisphere, which could not be explained by the increased infarct size alone. PMID- 1614593 TI - Inflammatory cell infiltrates vary in experimental primary and metastatic brain tumors. AB - We have studied the cellular immune response that accompanies primary and metastatic brain cancers induced experimentally in rats by inoculation of RG-2 glioma and Walker 256 (W256) carcinoma cells, respectively. The inflammatory cell infiltrates were characterized with lectin histochemistry to visualize microglial cells and macrophages and with immunohistochemistry, using a panel of monoclonal antibodies, to detect major histocompatibility complex (MHC), lymphocytic, and macrophage antigens. The metastatic tumor was composed of a loose stroma with multiple, often large, necrotic areas, whereas the RG-2 glioma was composed of a dense collection of tumor cells showing only rare necrotic foci. Both tumor types were heavily infiltrated with microglia and/or macrophages, and these were positive for MHC Class II (Ia) antigens. Expression of MHC Class I antigens was absent from RG-2 glioma cells, but it was present in W256 metastatic carcinoma cells. The metastatic tumor was also characterized by a much heavier infiltrate of lymphocytes, as shown by the presence of cells positive for CD4, CD8, and leukocyte common antigens. These lymphocytic markers were absent from reactive microglia in the W256 carcinoma, whereas they were present in the RG-2 glioma. Polymorphonuclear leukocytes were seen only in the metastatic tumor. Our study delineates differences between the inflammatory cell infiltrates found in metastatic brain tumors and those found in primary brain tumors. The differences in cell composition and immunophenotype may indicate a more effective antitumor response in the metastatic tumor that could account for the observed tissue destruction. PMID- 1614594 TI - Localization of sensorimotor cortex: the influence of Sherrington and Cushing on the modern concept. AB - According to Penfield, the work of Charles Sherrington's laboratory forced a change from the long-held concept of a broad, overlapping sensorimotor cortex to the concept of a narrow, discrete pre-Rolandic motor cortex separate from the post-Rolandic sensory strip. Harvey Cushing, one of the founders of modern neurosurgery, coined the term narrow motor strip. Cushing also appears to have been the first to color the precentral gyrus in a mosaic pattern and to use red coloring for the motor cortex and blue for the sensory cortex. Cushing's red and blue color coding is still used in textbooks, nearly 100 years later. In this article, we review the historical evolution of and the evidence for the concept of narrow and discrete motor and sensory strips anterior and posterior to the Rolandic cortex. A review of the historical development of the concept and recent physiological studies reaffirms the proposition that the motor and sensory areas are much broader and more complex than they were thought to be in the classic teaching that originated with Sherrington and Cushing. PMID- 1614595 TI - Synovial cyst at the C1-C2 junction. AB - Intraspinal synovial or ganglion cysts of the cervical spine are rare. We present the third reported case of a degenerative articular cyst of the upper cervical spine, involving the quadrate ligament of the odontoid process. Magnetic resonance examination reveals typical images. A new, more general terminology is proposed. PMID- 1614597 TI - Malignant astrocytoma six years after the resection of a cerebral metastatic cardiac myxoma: case report. AB - We describe a woman who had a total resection of a cardiac myxoma followed 8 months later by a hemorrhage in the right frontal lobe secondary to extravascular metastasis of the myxoma. Six years later, after an asymptomatic follow-up, she developed a recurrence of left-sided seizures and an enhancing mass in the same location as the previous tumor. At operation, a malignant astrocytoma was demonstrated. Cardiac myxoma is a true neoplasm with benign histology, which may be associated with heart failure, systemic illness, or peripheral embolization. The neurological manifestations of embolization may include no symptoms, acute or delayed infarction, and intravascular proliferation with aneurysmal dilatation and potential for hemorrhage. The development of extravascular metastatic tumor deposits has been reported previously in only three histologically verified cases. Once the integrity of the blood vessel wall is destroyed by the tumor, a portal of entry is established for tumor cell proliferation in the brain parenchyma. There is no known association between a metastatic cardiac myxoma and a malignant glioma in the literature. Several possibilities for the occurrence of these two neoplasms are discussed. PMID- 1614596 TI - Painful tic convulsif caused by a brain tumor: case report and review of the literature. AB - Patient with painful tic convulsif caused by a brain tumor is presented. The patient was admitted with right trigeminal neuralgia and ipsilateral facial spasm, i.e., painful tic convulsif. Preoperative computed tomography scans showed no apparent abnormalities; however, surgery revealed that these symptoms were associated with a pearly tumor located in the cerebellopontine angle. Subtotal resection for the decompression of the right trigeminal and facial nerves was performed and resulted in complete relief of the symptoms. Histological examination demonstrated the tumor to be an epidermoid cyst. PMID- 1614598 TI - Aneurysmal peroneal nerve compression. AB - Vascular compression syndromes of the peroneal nerve are rare. The case history of a patient with a peroneal nerve compression caused by a true anterior tibial artery aneurysm is reported. The surgical excision of the aneurysm resulted in marked improvement. PMID- 1614599 TI - Intracranial osteolytic malignant meningiomas appearing as extracranial soft tissue masses. AB - Malignancy is rare in intracranial meningiomas. Although the topic is widely discussed, there is little agreement in the literature as to the histological and radiological features that warrant the diagnosis of malignant meningioma. Three patients are described who had soft-tissue masses and underlying osteolytic lesions on computed tomography. All three patients also had a large intracranial component that proved to be a malignant meningioma. Rarely do meningiomas have all three of these features. We propose that a meningioma causing osteolysis and soft-tissue extension should be considered malignant until proven otherwise. PMID- 1614600 TI - Cystic meningioma: report of three patients. AB - Three patients with cystic meningioma are reported. The computed tomographic scans or magnetic resonance images of these tumors resembled those of a glial or metastatic tumor with cystic or necrotic changes. There is no definitive method for preoperatively differentiating cystic meningiomas from the more common malignant glioma. Angiographic evaluation and collaboration with a neuropathologist are important for the recognition of these potentially curable neoplasms. PMID- 1614601 TI - Bilateral arteriovenous malformations: case report. AB - The authors describe a case of supratentorial bilateral arteriovenous malformations in a patient who suffered an intracerebral hemorrhage. It was radiologically demonstrated that the arteriovenous malformations were separate and bilateral, located in the temporal lobes. They were removed in two operations with preoperative embolization of one. The patient did well with no neurological damage. PMID- 1614602 TI - Intracerebral hemorrhage after combined anticoagulant-thrombolytic therapy for myocardial infarction: two case reports and a short review. AB - Intracerebral hemorrhage complicating anticoagulant-thrombolytic therapy for myocardial infarction is infrequent but is associated with grave prognostic implications. We report two cases and review current management recommendations. PMID- 1614603 TI - Sacral agenesis occurring in siblings: case report. AB - We report a rare incidence of sacral agenesis occurring in siblings. One of our patients had a low-lying conus, and untethering of the cord in the area of the filum terminale led to improvement in urinary symptoms. The need for aggressive investigation of patients with sacral agenesis and static neurological deficits is discussed. PMID- 1614604 TI - Intraoperative angiography and temporary balloon occlusion of the basilar artery as an adjunct to surgical clipping: technical note. AB - The direct surgical treatment of intracranial aneurysms is not always possible, especially in posterior circulation aneurysms. This is usually because of their complex anatomy and location next to the skull base and brain stem, where proximal vascular control is usually not attainable. Four patients at our institution underwent intraoperative transfemoral catheterization of the basilar artery with a nondetectable endovascular balloon for proximal control of the basilar artery. The flow control in the basilar artery was excellent and facilitated the surgery. Before surgery, each patient underwent the placement of a 10-cm 8-French femoral introducer sheath and were taken to the operating room where they were placed in a supine position and a subtemporal or pterional craniotomy was performed. After the initial exposure and before aneurysm manipulation, a nondetachable silicone balloon catheter was passed through an introducer catheter and was placed into the rostral basilar artery, using flow direction, microguidewires, and angiographic "road-mapping" techniques. In two patients, temporary basilar occlusion was used to collapse the aneurysm and to facilitate clip placement. In the third patient, intraoperative aneurysm rupture occurred and was controlled by temporary basilar artery occlusion. Using intraoperative angiography, complete aneurysm obliteration and vessel patency was confirmed in all four patients. All patients made a complete recovery except for initial postoperative third nerve palsies in three patients. This technique achieves intraoperative control of the basilar artery proximal to an aneurysm by the use of a nondetachable occlusive balloon in the basilar artery. An added benefit is the ease with which intraoperative angiography can be obtained in this context.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614605 TI - Modified supraorbital craniotomy: technical note. AB - The authors present a surgical approach that incorporates the frontal sinus and extends a supraorbital craniotomy to include the lateral orbital rim and zygoma. The craniotomy provides wide exposure of the anterior fossa, orbit, ipsilateral middle fossa, and cavernous sinus. The procedure can be performed easily, and the bone flaps can be secured rapidly back into the anatomical position at the time of closure. This modified supraorbital craniotomy is ideal for large benign lesions originating along the sphenoid wing or orbit that expand into the anterior fossa. PMID- 1614606 TI - A temporal transsylvian approach to anterior circulation aneurysms. AB - Operative management of cerebral aneurysms remains a technically challenging problem in modern neurosurgery despite major advances in microsurgical techniques. This is largely caused by the difficulty of exposing and handling these aneurysms, which are located around the circle of Willis at the base of the brain. Large cranial windows, generous brain retraction, and local brain resection have, at times, been employed to overcome these difficulties. In the present report, an exclusively temporal approach to the anterior aspect of the circle of Willis for surgical treatment of aneurysms arising from the anterior circulation is described. This approach limits the surgical preparation and the craniotomy to the temporal area, protects the temporal branch of the facial nerve from injury, and provides a superior cosmetic appearance soon after surgery. It provides a lateral transsylvian exposure to the base of the brain and thus permits the safe dissection and exposure of the aneurysms using microsurgical techniques with minimal, if any, retraction of the frontal lobe. The need for routine resection of the gyrus rectus for exposure of anterior communicating artery aneurysms is alleviated. This approach can be considered in patients harboring large or small incidental or acutely ruptured anterior circulation aneurysms. The outcome of 96 consecutive patients who underwent this procedure is described to illustrate its safety and effectiveness. PMID- 1614607 TI - Vestibular schwannoma (acoustic neuroma). Consensus development conference. PMID- 1614608 TI - Definition of contemporary surgical management in cisternal and parenchymatous cysticercosis cerebri. PMID- 1614609 TI - Pregnancy in patients with cerebrospinal fluid shunts: report of a series and review of the literature. PMID- 1614610 TI - Neurophysiological assessment outcomes of nonacquired immunodeficiency syndrome patients with primary central nervous system lymphoma before and after blood brain disruption chemotherapy. PMID- 1614611 TI - Afferent and efferent connections of cortical transplants implanted into the damaged sensorimotor area of the cerebral cortex of adult rats. PMID- 1614612 TI - Monosynaptic connections in the central nervous system of the edible snail: receptive fields of presynaptic neurons. PMID- 1614613 TI - Role of the lateral and medial hypothalamus in the reproduction of the motoric reaction which is a signal during the development of classical conditioned reflexes. AB - It has been demonstrated in experiments on three dogs that test electrostimulation of the lateral hypothalamus reproduces the motoric reaction which is the signal stimulus during the development of classical alimentary CR (83%) and does not reproduce it during the development of classical defensive CR (93%). The test electrostimulation of the medial divisions of the hypothalamus, like the electrostimulation of the LH, reproduces the "signal" motoric reaction, but in a smaller percent of cases (62%), during the development of classical alimentary CR, and does not reproduce it during the development of classical defensive CR. The reproduction of the signal motoric reaction during the electrostimulation of the LH is associated with the activation of a backward conditioned connection from the motivational structures of the hypothalamus to the representation of the signal stimulus in the motor cortex. PMID- 1614614 TI - Functional role of the neurospecific S-100 protein in the processes of memory. AB - The change in the content of S-100 protein in the brain in the presence of learning and an amnestic influence (administration of an M-cholinolytic), taking interhemispheric asymmetry into account, was studied in experiments on white rats. The action of S-100 protein and of an antiserum to this protein on the learned behavior of the rats were also investigated. It was established that the level of S-100 protein increases in the left and right hemispheres in the process of the development of an alimentary conditioned reflex. The disruption induced by the cholinolytic of the processes of the development of conditioned reflexes is accompanied by a decrease in the content of S-100 protein in the brain. Intracisternal administration of an M-cholinolytic and an antiserum to S-100 protein mutually potentiates their amnestic effect. PMID- 1614615 TI - Organization of network properties of cells in local and distributed neuronal networks of the brain of cats. AB - The network properties of neurons of the visual and motor cortex and of the lateral nucleus of the hypothalamus were investigated on the basis of identified interneuronal interactions, using the cross-correlation method of analysis, in cats with developed alimentary conditioned instrumental reflexes to light. The varied organization of the network properties of cortical neurons in the organization of local and distributed neuronal networks was demonstrated, namely: the predominance of divergent properties over convergent properties for large cells in local networks and the leveling out of these relationships in distributed networks. The neurons of the lateral nucleus of the hypothalamus had an equal representation of convergent and divergent properties in the organization of local and distributed networks. The network properties of neurons of the cortical and subcortical structures were manifested in the background, following the development of conditioned reflexes, and during extinction. Only the small cells of the visual cortex were functionally dependent and changed the relationship of network properties in local networks during the extinction of conditioned reflexes. PMID- 1614616 TI - Change in neuronal excitability in hippocampal sections of rats isolated after the destruction of the medial septal area. AB - The influence of chronic destruction of the medial septal area (MSA) on focal potentials (FP) of field CA1 evoked by stimulation of Schaffer collaterals was studied in experiments on viable sections of the hippocampus of rats. The preparation, incubation, and pickup of FP of the sections of the control and experimental groups were carried out in identical conditions using traditional methods. The amplitude-temporal of population EPSP and population spikes, their interdependence, and their dependence on the strength of the stimulating current were assessed using automated data analysis. It was demonstrated that coagulation of the MSA is accompanied by an increase in the excitability of neuronal complexes of the lateral portion of field CA1 which is manifested by the generation of multiple rhythmic discharges and the development of spike activity of the cells at a lower intensity of the synaptic inflow. It is hypothesized that destruction of the MSA leads to a relative attenuation of inhibitory control in the neuronal systems of field CA1, the elements of which are depolarized with anomalous synchronicity and generate rhythmic impulse trains. PMID- 1614617 TI - Features of the establishment of the spontaneous activity of neurons of the trigeminal sensory nuclei of viable sections of the rat brainstem in postnatal ontogenesis. AB - An attempt was made to characterize the features of the development of the neurons of the sensory trigeminal nuclei, a basic structure of the sensory support of alimentary behavior, in the late stages of postnatal ontogenesis. A technique involving viable sections of the brainstem of infant rats at the ages of two, four, and eight weeks was utilized. An increase with age in the number of neurons possessing spontaneous activity (44% at two weeks; 69% at eight weeks), an increase in the frequency of discharges, the appearance by the fourth week of a population of cells with high-frequency spontaneous activity, and an increase in the number of such neurons by the eighth week. Three types of background active neurons were distinguished: episodic, continuous, and group; and the dynamics of the change in the ratios of these types with age was demonstrated. Significant changes with age were not found in resting potentials, although a tendency to its increase takes place between the second and eighth weeks of postnatal development. PMID- 1614618 TI - Phosphorylation of the proteins of synaptic membranes during the emergence of prolonged dissociated states induced by carbacholine. PMID- 1614619 TI - Influence of superficial polarization of the cerebral cortex of the dog on extinctive inhibition. PMID- 1614620 TI - Morphometric analysis of synaptic contacts in the anterior limbic cortex in the endogenous psychoses. PMID- 1614621 TI - Synthesis of proteins in the critical periods of early postnatal ontogenesis: its role in the formation of intraspecies aggressive behavior of rats. AB - The significance of the synthesis of the protein in the brain for the formation of intraspecies aggressive behavior of isolated males in early postnatal ontogenesis, under the influence of social contacts, was revealed in experiments on 200 mongrel rats. Chronic administration of cycloheximide (0.5 mg/kg; intraperitoneally), a protein synthesis blocker at the stage of translation, to infant rats from the 15th to the 30th postnatal days, prior to daily three-hour sessions of contacts between them, disrupted the formation of intraspecies aggressive behavior. This was manifested at adult age by their hyperaggressivity and by changes in the proportions of various reactions in the integral act of aggressive behavior. PMID- 1614622 TI - Results of clinical and enzymatic immunoassay study of a neurospecific leucine aminopeptidase in neurological patients. PMID- 1614624 TI - A method for the diagnosis of interhemispheric brain asymmetry. PMID- 1614623 TI - Participation of glutamatergic and dopaminergic systems of the neostriatum in the organization of alimentary conditioned reflexes. AB - In this study the results of behavioral, neurophysiological, and morphological investigations in relation to the participation of the corticostriatonigral system in the organization of conditioned reflexes are presented. It was demonstrated in experiments on dogs that blockade of N-methyl-D-aspartate receptors of the caudate nucleus disrupts the realization of consolidated conditioned reflexes and renders their development more difficult. The blockade of quisqualate receptors facilitates the process of differentiation. Switching off of the dopaminergic input makes the development of positive conditioned reflexes more difficult. The reversible switching off of the substantia nigra leads to the reorganization of the neuronal activity of the caudate nucleus in response to the presentation of the conditional signal. Inhibitory nigral influences are directed primarily to the ventromedial divisions of the nucleus, while activating influences are directed to its dorsal segments. The topically organized connections of the motor regions of the cortex with the dorsal region of the caudate nucleus, and of the limbic regions with its ventromedial divisions were studied in morphological investigations on cats. A certain distinctiveness was identified of the spatial organization of the nigrostriatal projections. The data obtained are discussed from the point of view from the systemic organization of behavior. PMID- 1614625 TI - Beyond our borders. PMID- 1614626 TI - We made the list, but... PMID- 1614627 TI - Rethinking women's services. PMID- 1614628 TI - We're building peace. An interview with Licensatura Rosa Rodriguez Deras, Director, School of Medical Technology, National University of El Salvador. Interview by Patricia Moccia. PMID- 1614629 TI - We're building peace. An interview with Yolanda de Landos, Director of Nursing, School of Medical Technology, National University of El Salvador. Interview by Patricia Moccia. PMID- 1614631 TI - The decade for natural disaster reduction: the role of health care workers. AB - Disasters are occurring more frequently these days. Pickens, a Geneva-based journalist, examines how the World Health Organization suggests to cope with disasters. PMID- 1614630 TI - Karoshi: death from overwork--a nursing problem in Japan? AB - Japanese Nurses are overworked and underpaid; many of them leave the profession at about age 25 and get married. Will working conditions change so that more nurses remain nurses? PMID- 1614632 TI - Medical disaster relief in Switzerland: a brief overview. PMID- 1614633 TI - Health for all by the year 2000: where is it now?. Interview by Craig Little. PMID- 1614635 TI - Health care in Canada: the presumption of care. PMID- 1614634 TI - Comparison of national health care systems (as of 18 July 1991). PMID- 1614636 TI - Health and nutritional consequences of the 1991 Bangladesh cyclone. PMID- 1614637 TI - Unproven nutritional remedies and cancer. PMID- 1614638 TI - Buthionine sulfoximine, an experimental tool to induce glutathione deficiency: elucidation of glutathione and ascorbate in their role as antioxidants. AB - The development of buthionine sulfoximine, a selective inhibitor of glutathione biosynthesis, is an important new tool to elucidate the in vivo role of glutathione. Recent investigations have shown that ascorbic acid can serve as an essential antioxidant in the presence of severe glutathione deficiency. PMID- 1614639 TI - Choline: a conditionally essential nutrient for humans. AB - Tissue concentrations of choline decreased significantly while serum alanine aminotransferase activity, a marker of liver injury, increased sharply (by 50%) when healthy young adult men received a choline-free semisynthetic diet for three weeks. This study suggests that choline is an essential nutrient for humans when excess methionine and folate are not available in the diet. PMID- 1614640 TI - Gender differences in immune competence during copper deficiency. AB - Restriction of copper intake during lactation and postlactation periods reduced T cells and increased interleukin-2 receptors in isolated splenocytes from male, but not female, rats. However, a reduced in vitro proliferative response to phytohemagglutin (PHA) was seen in both male and female Cu-deficient rats. These findings suggest that Cu deficiency may inhibit proliferation at a step between early activation and DNA synthesis. PMID- 1614641 TI - Interspecies differences in folate metabolism. AB - The primary form of folate in the plasma of pigs is tetrahydrofolate. In contrast, 5-methyl-tetrahydrofolate comprises most of all of the plasma folate in humans and other animal species examined. High-affinity folate-binding proteins may be involved in governing this distribution of plasma folates. PMID- 1614642 TI - The new reference daily intakes: for better or for worse? AB - The introduction of the RDIs was well intentioned. However, there are scientific uncertainties and reasons for concerns about the proposed new nutrition standards. Adoption of the RDIs will inevitably lead to reduced intakes of critically important vitamins and minerals, will make it more difficult for members of nutritionally vulnerable groups to meet their nutrient needs, and will have undesirable effects on the health of the most needy by altering nutrition priorities and programs in this country. National nutrition standards remain with us for a long time. The U.S. RDAs have been in place for 18 years; any new standards need to be sound enough and safe enough to last as long. The proposed RDIs are clearly not of this caliber. PMID- 1614643 TI - Energy requirements in the elderly. AB - The major components of daily energy expenditure may change during aging. A review of current estimates of energy requirements leads to the conclusion that direct estimates of daily energy expenditure are desirable to confirm the validity of the present recommendations. A more extensive examination of the metabolic and nutritional significance of the major food fuel sources is necessary to further define human energy needs. PMID- 1614644 TI - The bat killer. PMID- 1614645 TI - Applying an abduction pillow correctly. PMID- 1614646 TI - How H.I.V. affects the eye. PMID- 1614647 TI - Assessing fibrin-split products. PMID- 1614648 TI - Responding to carbamate poisoning. PMID- 1614649 TI - Preventing a peripheral i.v. infection. PMID- 1614651 TI - The gift of life. PMID- 1614650 TI - Peak levels for vancomycin. PMID- 1614652 TI - From coma to discharge. The story of a roller coaster recovery. PMID- 1614653 TI - Exploring misconceptions about breast cancer. PMID- 1614654 TI - Caring for the patient with a pigtail drainage catheter. PMID- 1614655 TI - Charting the future of emergency drug protocols. PMID- 1614656 TI - What you need to know about advance directives. PMID- 1614657 TI - S.I.A.D.H. Is your patient at risk? PMID- 1614658 TI - Just a minute. PMID- 1614659 TI - Death with dignity. PMID- 1614660 TI - Managing cardiovascular conditions. PMID- 1614661 TI - Transtracheal catheter tips. PMID- 1614662 TI - Myths & facts ... about depression. PMID- 1614663 TI - Learning to say no. PMID- 1614664 TI - Back to school. A guide for easing the pain. PMID- 1614665 TI - Intensive care for the elderly: should the gates remain open? PMID- 1614666 TI - Osseous sarcoidosis, radiologic imaging, and physician interaction. PMID- 1614667 TI - Impact of do-not-resuscitate legislation on the use of cardiopulmonary resuscitation in three teaching hospitals. AB - Under New York State's unique do-not-resuscitate law, patients admitted to a hospital are assumed to consent to cardiopulmonary resuscitation unless a do-not resuscitate order has been written in accordance with specific stipulations. This study was undertaken to determine if the law would significantly change the use of cardiopulmonary resuscitation. The charts of 952 patients who died on the medical services of Bellevue, New York University, and New York Veterans hospitals during the 12-month periods before and after the law went into effect were reviewed. The proportion of patients undergoing cardiopulmonary resuscitation was determined. To take into account the effects of potential confounders (ie, hospital, sex, race or ethnic group, age, diagnosis), a multiple logistic regression analysis was performed. The relative risk for cardiopulmonary resuscitation was found to be 0.81, (95% confidence interval: 0.59-1.10) after the law as compared with before, which was not statistically significant. Although patients with chronic or potentially reversible illness were much more likely than those with hopeless illness to undergo cardiopulmonary resuscitation (relative risk of 7.08 [3.23-15.54] and 12.89 [8.71-19.07], respectively), the data failed to show that the law had an impact on the use of cardiopulmonary resuscitation in any of the disease categories. Total use of formal do-not resuscitate orders increased from 32.7% to 83.9% (p less than .0001), although at Bellevue, where documentation was high before the law, no further increase occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614668 TI - Contact investigation and isoniazid chemoprophylaxis in New York City, 1979-1987. AB - The Bureau of Tuberculosis of the New York City Department of Health has carried out investigations of contacts to active cases of tuberculosis for many years. In addition, the Bureau has undertaken tuberculosis screening, with tuberculin testing and by radiography where indicated, of persons for employment purposes, school attendance, and for various other reasons. In 1969, the Bureau began providing isoniazid chemoprophylaxis; since then, more than 150,000 persons have been given isoniazid. Several isoniazid chemoprophylaxis effectiveness trials of chemoprophylaxis are achieved, the frequency of developing tuberculosis in one's lifetime would be reduced by 50%-70% by the time treatment is completed, according to several studies. On the basis of the beneficial results of these trials, the Bureau of Tuberculosis introduced the use of isoniazid chemoprophylaxis. This study was undertaken to assess the acceptability of isoniazid chemoprophylaxis and the success of contact investigation under both regular clinical conditions and uncontrolled conditions. PMID- 1614669 TI - Pigeons as a remedy (segulah) for jaundice. PMID- 1614670 TI - Pulmonary cavitary disease. PMID- 1614671 TI - The story of Lassa fever. Part I: Discovering the disease. PMID- 1614672 TI - A history of the Women's Medical Society of New York State. PMID- 1614673 TI - Lytic osseous destruction in vertebral sarcoidosis. PMID- 1614674 TI - Clavicular resection in the exposure and resection of malignant tumors. PMID- 1614675 TI - Renal angiomyolipoma presenting as a retroperitoneal mass following thrombolytic therapy for acute myocardial infarction. PMID- 1614676 TI - Neutropenia induced by low-dose captopril. PMID- 1614677 TI - Hyperbilirubinemia in the term infant. PMID- 1614678 TI - Exercise and pregnancy: a review of maternal and fetal effects. PMID- 1614679 TI - Energy requirements in pregnancy: a review. AB - The traditional estimates of the additional energy requirements during pregnancy are approximately 300 calories per day or 80,000 calories for a full-term pregnancy. Recently these estimates have been challenged as being excessive, especially for non-Western populations. In light of recent studies and advances in methodology, the purpose of this paper is to review 1) the components of energy expenditure, 2) the different methods of assessing energy expenditure, 3) various factors that may affect energy expenditure during gestation, and 4) the recent literature on energy expenditure in pregnancy. The available data suggest that the energy requirements in pregnancy are varied and depend on the population being examined. Furthermore, additional studies are needed in order to clarify these issues in various normal populations as well as in populations at risk for fetal growth abnormalities. PMID- 1614680 TI - Hormonal replacement therapy in postmenopausal women and cardiovascular disease: an overview. PMID- 1614681 TI - Engineers encourage universities to emphasize safety in curriculum. PMID- 1614682 TI - Ergonomics at UAW-Ford. PMID- 1614683 TI - Personal experience on horizontal glottectomy. Critical evaluation of long-term results. PMID- 1614684 TI - Elective radiotherapy of the neck in patients with squamous cell carcinoma of the head and neck. AB - A prospectively recorded 5-year series of 254 patients receiving elective neck irradiation is evaluated. All had clinically negative necks and initial control at the primary site. Forty-seven percent of the patients had T3-4 tumours. Radiotherapy was delivered from a megavolt source at 2 Gy/day 5 days a week to a total dose of 46-50 Gy. All but 3 patients completed the treatment as planned. Neither tumour stage nor site of the primary tumour was related to the incidence of regional recurrences. Of 30 patients receiving 46-49 Gy, 5 died from neck node recurrences. Of 221 patients treated to 50 Gy or more, 16 (7.2%) developed regional recurrences. Two of these recurrences were avoided, giving a regional failure rate of 6.3%. As a whole, 7.8% died from regional, 11.4% from local, and 3.1% from distant recurrences. PMID- 1614685 TI - Vestibular disturbance after myelography. Contrast media in the internal auditory canal. AB - Two cases of vestibular disturbance caused by residual oily contrast medium in the internal auditory canals after myelography are reported. Nystagmus towards the affected side and normal caloric responses were observed; therefore, contrast media are considered to act as irritants to the vestibular nerve. PMID- 1614686 TI - Sensorineural hearing loss associated with otitis media with effusion. AB - The clinical records of 1,372 cases of otitis media with effusion (OME) treated during the past 10 years were reviewed in search of associations with sensorineural hearing loss (SNHL). In 14 cases (1.0%), the development of SNHL was considered to be etiologically related to OME. These 14 cases were classified into two groups. In group A, which consisted of 5 cases, the clinical feature was acute onset of SNHL and gradual improvement. In group B of 9 cases, SNHL progressed gradually or insidiously and did not improve. Different pathophysiology may be assumed to underlie these two groups. The results of this study demonstrate that we have to pay attention to a possible development of SNHL during the course of OME. PMID- 1614687 TI - Idiopathic sudden hearing loss and disturbance of iron metabolism. A clinical survey of 426 cases. AB - The role of disturbances of the iron metabolism (DIM) in idiopathic sudden hearing loss (ISHL) was investigated in 426 patients with ISHL who received iron therapy, anti-DIM medication, vitamins, and a combined regimen in a randomized study which was stratified by stages and groups. Low concentrations of haemoglobin, serum iron, serum ferritin, and red cell basic ferritin as well as abnormal circadian variations in the serum iron level were observed. The results were significantly better in patients receiving iron therapy than in those receiving anti-DIM medication, vitamins, and the combined regimen. Hearing improvement was achieved in 53.26% of the patients whose treatment started later than 3 months after the onset of the disease. The clinical association of DIM and ISHL is discussed. PMID- 1614688 TI - Electronystagmographic features in some peripheral and central vestibular disorders: application of multiple discriminant analysis of electronystagmographic parameters. AB - In routine clinical electronystagmographic (ENG) tests (postrotatory, optokinetic, caloric and tracking tests), eye movement signals were analyzed and a multiple discriminant analysis was carried out with the aid of a microcomputer. Six parameters were selected and, based on these, two functions for discriminating between peripheral and central disorders were established. Discrimination between 35 patients with peripheral lesions and 15 patients with central lesions was made with a correct classification rate of 97.1 and 86.7%, respectively. These rates are significantly higher than that of any single ENG test analysis. Our results indicate that the clinical application of ENG can be improved by searching for more sensitive ENG parameters and adopting the comprehensive analysis approach. PMID- 1614689 TI - Functional study of the eustachian tube with sequential scintigraphy. AB - The authors investigated the tubal function by means of sequential scintigraphy in 16 patients affected by chronic otitis media and in 3 patients with posttraumatic perforation of the tympanic membrane. Evaluated parameters were: appearance time (AT), radioactivity peak time, rise time in the tympanic cavity, eustachian tube and rhinopharynx, and radioactivity percent values passed in the rhinopharynx. The tubal pressure-equilibrating function was determined by means of the manometer pump section of the impedance meter. A significant relationship between the pressure-equilibrating function and the tubal scintigraphy parameters has been detected. The variability of the AT in the tube and the almost constant time needed by the radioactive tracer to go through the tube and reach the rhinopharynx could indicate that a major role in the tympanic cavity drainage is played by the tympanic ostium and the surrounding mucosa. PMID- 1614690 TI - Culture and cryopreservation of chondrocytes from human cartilage: relevance for cartilage allografting in otolaryngology. AB - One of the reasons for failure of cartilage allografts is the impaired condition of the transplant during storage. In this paper we describe methods for the isolation and culture of viable chondrocytes obtained from nasal septum cartilage. Furthermore, we evaluate the possibility of growing such specific chondrocytes under culture conditions and storing them in a frozen state. Age dependent differences were observed in the growth rate of the cultured cells. Our results confirm that chondrocytes survive freezing and remain able to proliferate. Knowledge gained from this study may be applied to the culture and freezing of viable intact cartilage for use in reconstructive surgery in otolaryngology. PMID- 1614691 TI - Immunohistochemical study of the fourth cell type in the olfactory epithelium in guinea pigs and in a patient. AB - The mammalian olfactory epithelium consists of supporting cells, olfactory receptor cells, basal cells and a fourth cell type, which has recently been discovered. In this study we examine this fourth cell type using immunohistochemical techniques. Anti-Purkinje-specific spot-35 protein (S-35), anti-S-100 protein (S-100), anti-neuron-specific enolase (NSE), antichromogranin A and antisynaptophysin antisera were used for the immunostaining. The fourth cell type immunoreacted only to anti-S-35 antiserum and did not react to other antisera in guinea pigs. On the other hand, in the human S-100 immunoreactivity was seen in the fourth cell type as well as weak reactivity to S-35. NSE immunoreactivity was found only in the olfactory receptor cells of guinea pigs and the human. From these results it is assumed that this fourth cell type is a second chemoreceptor different from the olfactory receptor cells because S-35 and S-100 are Ca(++)-binding proteins. PMID- 1614692 TI - Empty sella syndrome, diagnosed as allergic rhinitis. AB - Unilateral cerebrospinal fluid (CSF) rhinorrhea as the only manifestation of the primary empty sella syndrome is a rare event. A case of a middle-aged male patient complaining for intermittent unilateral rhinorrhea, which started 5 months earlier, is reported. The persistence of this state was attributed to an allergic rhinitis. The initial work-up excluded the above diagnosis and an erroneous radiological diagnosis led to a puncture of the left maxillary sinus. A lateral X-ray of the skull and CT scan led to the diagnosis of empty sella syndrome, possibly due to an adenoma or a meningocele. PMID- 1614693 TI - Phlegmonous and abscess-forming ENT infections: comparative efficacy of ceftriaxone versus amoxicillin-clavulanic acid. AB - In this randomized trial, 100 patients received ceftriaxone or amoxicillin clavulanic acid in phlegmonous or abscess-forming ENT infections. Clinical and bacteriological results confirm that both antibiotics are equally effective, the advantage of ceftriaxone being one administration a day. Drainage surgery is necessary when an abscess has already formed. In 4 cases (ceftriaxone: 3; amoxicillin-clavulanic acid: 1), no positive response could be observed. Systemic and local tolerance was, as a general rule, excellent, and side effects were reported in 3 cases of the ceftriaxone group and in 3 cases of the amoxicillin clavulanic acid group. PMID- 1614694 TI - Continuously improving patient care: practical lessons and an assessment tool from the National ICU Study. AB - Pressure for hospitals to maintain quality while lowering cost or provide greater quality at a given level of cost is particularly critical in intensive care services for which it is increasingly difficult to match revenues with costs, given reimbursement limits. At the same time, twofold to threefold differences in intensive care unit risk-adjusted mortality have been reported. This article provides a model for thinking about continuous improvement of intensive care services, draws on the National ICU Study to identify fundamental organizational and managerial processes associated with better performance, and offers a validated assessment instrument to be used as a tool for continuous improvement. PMID- 1614695 TI - The Achilles' heel of quality management: the human quotient. PMID- 1614696 TI - Cross-functional, integrative team decision making: essential for effective QI in health care. AB - Quality improvement methods first developed in industry can be applied in health care, but major adjustments in the traditional health care organization are needed for continuous improvement processes to work. One change is establishing cross-functional or multidisciplinary teams to carry out integrative decision making in the place of departmental hierarchical decision making within the functional areas and disciplines. This article cites examples from experience with one service process--delivery of care to newborns--and examines techniques from the group behavior and conflict resolution literature which could enhance the success of cross-functional teams in health care organizations. PMID- 1614697 TI - A consumer guide for marketing medical services: one institution's experience. AB - This paper describes the Cleveland Clinic Foundation's experience with the development and implementation of a 20-page quality indicator consumer guide for patients with or at risk of developing coronary artery disease. The guide, which provides six "quality indicators," was designed to enable patients to evaluate and compare quality-related information when choosing a provider. Design elements for the guide included a user-friendly format to offset the amount of information consumers are asked to absorb. Data on inquiries showed that the majority were women (53%) and adults under the age of 65 years (57%). Although the media criticized the guide as a marketing tool, it represents an effort to educate consumers about the importance of research when choosing a provider. PMID- 1614698 TI - [Extrahepatic cholestasis in infancy and childhood: the role of ultrasonography]. AB - Of 23 children with extrahepatic cholestatic syndromes, who were studied with sonography, there were found to have biliary atresia, choledochal cyst, cholelithiasis, stenosis of bile duct, gallbladder duplication, cholecystitis. Ultrasonography is the most useful initial investigation of choice, and in most of the cases the only investigation. PMID- 1614699 TI - [Diagnosis of chronic myeloproliferative diseases based on bone marrow biopsy]. AB - The bone marrow biopsies and laboratory data of 248 patients with untreated chronic myeloproliferative disorders have been evaluated according to the Hannover Classification. 47.6 per cent of the cases were classed as primary or basic diseases, including chronic myeloid leukaemia common type, chronic myeloid leukaemia megakaryocytic type, chronic megakaryocytic-granulocytic myelosis, polycythaemia vera and essential thrombocythaemia. In 52.4 per cent of the biopsies the advanced stages of the primary diseases like increase of fibers and loss of differentiation were noted; the increase of fibers in myeloid leukaemia megakaryocytic type and in chronic megakaryocytic-granulocytic myelosis, and loss of differentiation in chronic myeloid leukaemia common type were frequently noted. In 14.1 per cent of the cases the advanced myelofibrosis and blast cell accumulations obscured the histological features of the primary disease, therefore these cases were placed in the unclassifiable group. The cases without increase of fibers and loss of differentiation accounted for only 4 per cent of the unclassifiable category. Leucocyte and platelet count as well as haematocrit values showed considerable overlapping and scattering and were generally lower in cases which developed myelofibrosis. PMID- 1614700 TI - [Long-term phenytoin (Diphedan) therapy leading to IgA nephropathy]. AB - A single case of IgA nephropathy with a concomitant tubulointerstitial nephritis, developing during a long-term phenytoin therapy is reported. The prolonged phenytoin therapy did neither prevent the transitional increases of serum IgA level nor ward off deterioration of the histological alterations. This case suggests that acute tubulointerstitial nephritis may have played a role in the mesangial trapping of IgA immunocomplexes. PMID- 1614701 TI - [Treatment of cholelithiasis. Professional recommendation--1992]. PMID- 1614702 TI - [Jozsef Szentgyorgyi (1765-1832]. PMID- 1614703 TI - [Jeno Jendrassik and the beginning of experimental physiology in Hungary]. PMID- 1614704 TI - [Cosmetic aspects of dentistry at the beginning of the 19th century]. PMID- 1614706 TI - [Comment on the article discussing the system of family medicine and laboratory diagnosis, by Maria Nemeth, published in Orvosi Hetilap vol.135, p. 575]. PMID- 1614705 TI - [Waldenstrom's macroglobulinemia?]. PMID- 1614708 TI - Painting with too broad a brush? PMID- 1614707 TI - [Parasystole?]. PMID- 1614709 TI - Understanding advance directives and amendments to guardianship law. AB - In April, Pennsylvania became one of the last states in the country to statutorily recognize living wills. In addition, Pennsylvania guardianship statutes have been amended. This article describes those changes and informs physicians of their responsibilities when patients have executed living wills or when guardians have been appointed by the courts. PMID- 1614710 TI - Plans proceed to publish physician-specific data. AB - Physicians should be aware that the release of physician-specific information by the Pennsylvania Health Care Cost Containment Council (PHC4) may have a significant impact on decisions made by patients or potential patients. This article, which outlines PHC4's proposed Research Plan about coronary artery bypass graft (CABG) surgery and related issues, is a follow-up to "First Report Card for Physicians Due This Summer" [Pennsylvania Medicine, May 1992] PMID- 1614711 TI - Health views from the Senate: Part Two. Interview by Maria T. Montesano. PMID- 1614712 TI - An update on Lyme disease in Pennsylvania. PMID- 1614713 TI - How does KePRO compare? PMID- 1614714 TI - Dealing with stress in the physician's marriage. AB - Practicing medicine in the 1990s brings a high-stress lifestyle, and no one knows that better than the spouse of a physician. While television and cinema have portrayed the medical family as an all-American ideal, the reality can be very different. PMID- 1614715 TI - Motivating employees to be team players. The Health Care Group. PMID- 1614716 TI - New antibiotics for skin and skin structure infections. PMID- 1614717 TI - Pedicle screw fixation in the management of unstable thoracolumbar spine injuries. AB - Pedicle screw fixation provides rigid segmental stabilization of the thoracolumbar spine. A wide range of conditions that can cause instability of the thoracolumbar spine can be treated using this technique. The increasing popularity of pedicle screw fixation has resulted in new knowledge concerning pedicle anatomy and the biomechanics of this method of fixation. The preliminary results have clarified both the indications and the limitations of this procedure. Successful results using pedicle screws require prudent patient selection, thorough preoperative preparation, and a high level of surgical expertise. PMID- 1614718 TI - Basic principles and clinical uses of screws and bolts. AB - The orthopaedic surgeon uses screws for interfragmentary fixation, fastening soft tissue to bone, or holding plates or nails to bone. The most common function of screws is to fix bone to bone. This article reviews the design parameters and types of screws used in orthopaedic surgery. PMID- 1614719 TI - Review of treatment results for Kienbock's disease. AB - A review of the literature reveals that Kienbock's disease has been treated in many different ways. Excision of the lunate, with or without replacement arthroplasty, and joint-leveling procedures (radial shortening or ulnar lengthening) are the most popular procedures, but other methods of treatment (nonoperative, wrist denervation, lunate revascularization, intercarpal arthrodesis and proximal-row carpectomy) have also been performed. Based on our current understanding of the etiology, a joint-leveling procedure seems to make the most sense when surgery is indicated. However, other procedures have yielded a high success rate as well. PMID- 1614720 TI - The effects of fibular and talar displacement on joint contact areas about the ankle. AB - The purpose of this study was to advance prior techniques and studies regarding the effects of fibular and talar displacement of contact areas of the tibio-talar joint. Type IV supination external rotation injuries were experimentally created on five fresh cadaveric specimens. Tibio-talar contact and peak pressures were measured using Fuji pressure-sensitive film with the talus in a neutral position and then displaced 1, 3, 4, 5, and 8 mm laterally as well as a repeat measurement following reduction and plate fixation. Results demonstrated a 50% reduction in contact area with only 1 mm of talar displacement along with a linear increase in average peak pressures. Reapproximation of the fibular osteotomy with a plate and rereduction of the talus allowed for return to normal pretesting contact areas. This study confirms prior studies demonstrating the significance of 1 mm of talar displacement in regards to marked reduction in contact area of the tibio-talar joints. In addition, restoration of the normal anatomy and fixation of the osteotomy allows for return of normal contact areas. PMID- 1614721 TI - Gait analysis in pediatric lower extremity amputees. AB - Walking function in 56 children with lower extremity amputations was assessed using a questionnaire and gait analysis. Children with prosthetic lower extremities can be very functional in society, often participating in sports. Limitations are proportional to the extent of the missing limbs. As a group, pediatric amputees walk more slowly than their normal peers with a slower cadence and a longer stride length. Pediatric amputees have higher heart rates when walking than normal children, but they seem willing to pay a higher physiologic price for ambulation. PMID- 1614722 TI - Lower spinal mobility and external immobilization in the normal and pathologic condition. AB - The study presented here used lateral flexion and extension roentgenograms to determine lumbosacral motion in healthy persons and in patients with spondylolisthesis. The lumbosacral corset, Jewett extension brace, and plastic thoracolumbosacral orthosis (TLSO) were then placed and repeat roentgenograms were done to see if effective immobilization could be obtained. Although individual variation existed, there appeared to be no significant difference in lower lumbar motion between the two groups studied, and the orthotics acted in a similar fashion on both the volunteers and the patients. The lumbosacral corset was unable to immobilize the L3-S1 levels. There was a statistically significant decrease in the average lateral disk space motion at L3-4 and L4-5 with the use of the Jewett brace and the TLSO (P less than .01); however, the motion was never completely eliminated. No brace could adequately immobilize the L5-S1 level, and some people demonstrated increased motion at this level while wearing the orthotics. PMID- 1614723 TI - Superficial temporal artery laceration. A complication of skull tong traction. AB - Complications associated with the use of skull tongs are not uncommon. We report a case of superficial temporal artery injury as a complication of Gardner-Wells tong application. Chronic recurrent episodes of pulsatile bleeding from the pin site necessitated arterial ligation to control the bleeding. PMID- 1614724 TI - Imaging rounds. Bilateral condensing osteitis of the clavicles. AB - The following case illustrates the roentgenographic and clinical findings of a condition of interest to the orthopaedic surgeon. The initial history, physical findings, and roentgenographic examinations are found on the first two pages. The following pages present the final clinical and roentgenographic differential diagnosis. PMID- 1614725 TI - A method for removal of broken vertebral screws. AB - A method for removal of a broken vertebral screw is described using an easily obtained 5/64-inch tungsten drill bit and a #1 screw extractor. It allows removal of the screw while retaining pedicle integrity and also minimizes potential nerve root compromise. PMID- 1614726 TI - Inserting distal screws into interlocking IM nails. AB - The use of interlocking IM nails is commonplace in major trauma centers. Currently, an accurate guide for inserting the distal screws is not available. Most centers use the "free-hand" technique. Every surgeon must be familiar with this method to insert the screws. We describe our protocol for inserting the distal screws into interlocking IM nails. PMID- 1614727 TI - Drill sleeve for pedicle screw fixation. AB - Pedicle screw fixation is a popular method of fixation of the spine. Placement of screw and prevention of injury are surgeon dependent. We describe an easily made drill sleeve and depth gauge to assist in the preparation of the vertebral pedicle for pedicle screw application. Use of this device will help prevent soft tissue injury and overpenetration of the drill in the vertebral body. PMID- 1614729 TI - The laboratory maintenance of Sanguinicola inermis Plehn, 1905 (Digenea: Sanguinicolidae). AB - Methodology is described for the laboratory maintenance of the life-cycle of Sanguinicola inermis, using common carp (Cyprinus carpio) as the definitive host and Lymnaea peregra as the intermediate host. Lymnaea auricularia was also infected but is not considered to be a suitable laboratory host. Tench (Tinca tinca) were susceptible to infection at high cercarial doses but subsequent infection rates were low. Goldfish (Carassius auratus) and Lymnaea stagnalis were refractory to laboratory infection. PMID- 1614728 TI - Identification and characterization of two repetitive non-variable antigens from African trypanosomes which are recognized early during infection. AB - The present paper describes two repetitive proteins representing common antigens of African trypanosomes which are non-variant and which are recognized early in infection by the host immune system. These antigens were identified by their ability to immunoreact with bovine serum taken during the early phase of a cyclic trypanosomal infection. Screening of a cDNA library from T. b. gambiense with such early infection serum identified a protein which contains a repetitive motif consisting of 68 amino acid repeat units (GM6). Immunofluorescence and immunogold electron microscopy revealed that GM6 is located on fibres which connect the microtubules of the membrane skeleton with the flagellum. A second repetitive antigen detected by this serum is MARP1 (microtubule-associated repetitive protein 1), a protein previously characterized in this laboratory as a high molecular weight component of the membrane skeleton, which consists of more than 50 tandemly repeated, near-identical 38 amino acid repeat units. Beta galactosidase fusion products of both proteins demonstrated a strong immunoreactivity with sera from T. b. brucei and T. congolense-infected cattle. The result from this preliminary immunological evaluation indicates a high immunodiagnostic sensitivity (90%) of the two recombinant antigens which make them interesting candidates for immunodiagnosis of trypanosomiasis in cattle. PMID- 1614730 TI - Developmental changes of Echinococcus multilocularis metacestodes revealed by tegumental ultrastructure and lectin-binding sites. AB - Ultrastructural investigations (SEM, TEM) combined with lectin-binding analysis, have revealed concurrent modifications in tegumentary structure and surface glycoconjugates during the establishment and differentiation of Echinococcus multilocularis metacestodes in jirds. The laminated layer, which is amorphous and rich in polysaccharides when initially secreted by the young cyst, takes on a different appearance and has a different glycoconjugate composition according to whether the cyst becomes fertile or sterile. The laminated layer of fertile cysts transforms into a microfibrillar matrix, the protein content of which may increase while sugar content decreases during protoscolex differentiation. Independently of this structure, brood capsules, from which arise protoscoleces, are formed by invagination of the cyst tegument. The intense secretion of glycoconjugates from the brood capsule wall during invagination may serve to interact with host factors passing through the laminated layer. The combined use of ultrastructural study and lectin labelling has allowed the demonstration of an ultrastructural and biochemical gradient of differentiation of the protoscolex. Seven stages of differentiation have been described. The possibility that the excreted-secreted tegumentary glycoconjugates, revealed by lectin labelling during protoscolex differentiation, might be the gradual biochemical expression of one or several stimuli implicated in the phenomenon of protoscolex maturation, is discussed. PMID- 1614731 TI - Immunoepidemiology of Ascaris lumbricoides: relationships between antibody specificities, exposure and infection in a human community. AB - The serum antibody responses of 124 people naturally exposed to Ascaris lumbricoides infection were analysed by immunoprecipitation of radio-isotope labelled 3rd- and 4th-stage larval Ascaris suum excretory and secretory antigens (L3/4 ES). Profiles of antigens recognized were visualized by polyacrylamide gel electrophoresis (SDS-PAGE), and the band intensities of the 12 major precipitated antigens were individually scored. Most subjects were seropositive, but considerable variation was observed in the amount of total and individual ES antigens precipitated. The sex- and age-related profiles of antibody levels followed similar patterns to those of egg output. In addition, total antibody scores of individuals were closely correlated (r = 0.47-0.52) with their eggs per gram of faeces (e.p.g.) collected 4 months after blood samples were taken. These findings suggest that antibody levels against larval ES antigens reflect recent exposure and are consistent with the hypothesis that establishment of adult worms is proportional to the number of larvae that recently migrated through the lung. PMID- 1614732 TI - Segregation and co-occurrence of larval cestodes in freshwater fishes in the Bothnian Bay, Finland. AB - Two autogenic (Triaenophorus crassus and T. nodulosus) and four allogenic (Diphyllobothrium latum, D. dendriticum, D. ditremum and Schistocephalus solidus) larval cestode species were found in 13 out of 31 fish species studied from the Bothnian Bay, NE Baltic. Gasterosteus aculeatus was the most heavily infected fish with 4 larval cestode species; for two of them (D. ditremum and S. solidus) the three-spined stickleback was found to be the required fish intermediate host. Among allogenic cestode species, those restricted to different definitive host species segregated their larval population in relation to the fish host, while, for example, D. ditremum and S. solidus, both maturing in fish-eating birds, had the highest percentage of co-occurrences. D. dendriticum, which had the widest range of definitive hosts, was found in the greatest number (8) of fish species and co-occurred with all other species found except T. crassus. The two autogenic species totally segregated their larval population from each other although they both require pike as definitive host. The ecological and evolutionary relationships behind the patterns found for larval cestodes are discussed. PMID- 1614733 TI - Sequential development of the immune response in rainbow trout [Oncorhynchus mykiss (Walbaum, 1792)] to experimental plerocercoid infections of Diphyllobothrium dendriticum (Nitzsch, 1824). AB - Development of the inflammatory response of rainbow trout to experimental infections with Diphyllobothrium dendriticum plerocercoids is described using light and electron microscopy. The cellular response to plerocercoids occurred within 2 weeks post-infection (p.i.). This was followed by an increase in leucocyte numbers during weeks 3-6 p.i., with full encapsulation of plerocercoids by week 6 p.i. Neutrophils were the first leucocytes to engage the developing plerocercoid, followed by large influxes of macrophages which transformed into epithelioid cells. With longer times p.i. the accumulation of different leucocyte types increased, and a blood vascular network developed. Full development of the composite cyst was characterized by fibroplasia, particularly at the periphery of the cyst, and the subsequent deposition of a collagenous tissue matrix. Enzyme linked immunosorbent assay (ELISA) examination of serum samples taken over the 20 week period showed that specific anti-D. dendriticum antibody titres were first detected at 5 weeks p.i. and increased to a maximum by 11 weeks p.i. PMID- 1614734 TI - Experimental population dynamics of Rhabdias bufonis (Nematoda) in toads (Bufo bufo): density-dependence in the primary infection. AB - Density-dependence in worm establishment, numbers, biomass and larval production were examined in primary infections of 0, 10, 40, 80 and 160 larvae of the lung nematode, Rhabdias bufonis in the common toad, Bufo bufo. The infection procedure established 4 non-overlapping levels of infection which persisted until 6 weeks post-infection (p.i.), after which there was an overall decline up to 12 weeks p.i. Worm numbers had no direct effect on adult worm survival but temporal changes in worm weight were density-dependent. Adult worm establishment in the lungs declined significantly as the numbers of worms in the lungs increased. At the lowest exposure dose, 86% of the larvae administered reached maturity in the lungs while at the highest, only 37% did so. Also, the numbers of immature larvae outside the lungs increased as adult worm numbers increased. Both features provide evidence for a threshold limit to the numbers of worms maturing in the lungs. Worm numbers also affected larval output per host and per capita fecundity. A significant positive relationship between per capita fecundity and per capita worm weight suggested that density-dependence acted primarily to constrain the growth of individual worms. Finally, the constraints imposed on worm growth and fecundity were apparently relaxed when worm density decreased, providing evidence for density-dependent flexibility in per capita fecundity. Density-dependence in worm establishment and per capita fecundity are mechanisms which may potentially regulate this host-parasite interaction in the field. Both mechanisms may be functionally related to physical space limitations in the lungs, within which worms must compete for finite nutrients. PMID- 1614735 TI - Species richness in helminth communities: the importance of multiple congeners. AB - Using data sets derived from published literature, the contribution of congeneric species to helminth component community richness is evaluated. Consideration of the frequency distribution of congeners in relation to host and parasite groups reveals that the distributions are unimodal, that singletons are the commonest class and that the frequency of occurrence of congeners decreases with increasing number of species per genus. Congeners may be found in any group of hosts or parasites, but are more common amongst cestodes of aquatic birds. Two patterns of occurrence of congeneric species are recognized: one in which from a few to multiple congeners are found within a single helminth genus, exemplified by dactylogyrid monogeneans and cloacinid nematodes, and the other in which there is a simultaneous occurrence of congenerics and confamilials such that there are several genera involved, but each represented by fewer species, exemplified by strongyles in horses. The question of whether these patterns can be considered examples of species flocks is discussed. We conclude that multiple congeners and species flocks are interesting phenomena but, except in isolated cases, they make insignificant contributions to community richness. PMID- 1614736 TI - Studies on a murine model of congenital toxoplasmosis: vertical disease transmission only occurs in BALB/c mice infected for the first time during pregnancy. AB - The incidence of congenital toxoplasmosis was determined by an ELISA in the litters of BALB/c mice which had been infected 8 weeks before mating, on day 12 of pregnancy, or on both these occasions. Of those mice given the infection for the first time on day 12 of pregnancy, 5 out of 6 gave birth to infected litters with approximately 50% of the individuals in each litter being infected. BALB/c mice which had been infected 8 weeks before mating did not give birth to infected litters, even if they were reinfected on day 12 of pregnancy. Following infection BALB/c mice were found to harbour significantly fewer tissue cysts than the congenic H-2 derivative BALB/K strain. However, chronically infected BALB/K mice also failed to produce infected litters, indicating that tissue cyst burden in the dam did not influence congenital infection at least on the BALB background. This study demonstrates that BALB/c dams chronically infected with Toxoplasma gondii, have immunity capable of protecting their embryos from congenital infection, even if the dams are reinfected during pregnancy. Our results demonstrate that the BALB/c mouse can be used as a model of human or ovine congenital T. gondii infection suitable for testing putative vaccines. PMID- 1614737 TI - A monoclonal-based IgM capture ELISA for detection of antibodies to 22 and 41 kDa membrane antigens of Toxoplasma gondii. AB - A murine monoclonal antibody which reacts to 22 and 41 kDa Toxoplasma gondii surface antigens was employed in an IgM capture enzyme-linked immunosorbent assay (ELISA). A total of 125 patients' sera were tested in the monoclonal-based assay. When compared with a commercial ELISA test (Abbott Toxo-M EIA) which uses polyclonal anti-T. gondii antibodies, good correlation (Pearsons coefficient r = 0.91) was observed. The specificity of the assay was studied by testing a panel of control sera obtained from healthy individuals and blood transfusion donors; all sera gave negative results. Serum samples positive for T. gondii antibodies were treated with 2-mercaptoethanol (2-ME) to demonstrate the specificity of the test for IgM antibodies. Reactivity of these sera was lost after the treatment. The test is not subject to interference by rheumatoid factor as sera positive for rheumatoid factor were negative in the assay. Reproducibility was good with the coefficients of variation for within-day tests below 10% and not exceeding 18% for day-to-day tests. The monoclonal-based assay is simple to perform and appears to be a viable test for diagnosis of T. gondii infection. PMID- 1614738 TI - Modulation of the activity of the internal defence system of the pond snail Lymnaea stagnalis by the avian schistosome Trichobilharzia ocellata. AB - Effects of infection with the avian schistosome Trichobilharzia ocellata on the activity of the internal defence system of the intermediate snail host Lymnaea stagnalis were studied, utilizing an in vitro phagocytosis assay for determining haemocyte activity. A distinction was made between plasma- and cell-associated effects. The period immediately after penetration of the parasite into the snail host (1.5-72 h post-exposure (p.e.)) was extensively studied. In addition, several time-points coinciding with the later-successive-stages of parasite development (2, 4, 6, 8 and 10 weeks p.e.) were investigated. Plasma-associated enhancement of defence activity was found between 1.5 and 6 h p.e., followed by plasma-associated suppression between 12 and 72 h p.e. A cell-associated activation was found between 1.5 and 6 h p.e. and also at 8 and 10 weeks p.e. How these effects on the defence system may be related to phenomena observed in infected snails at these time-points is discussed. PMID- 1614739 TI - The in vitro transformation of the miracidium to the mother sporocyst of Schistosoma margrebowiei; changes in the parasite surface and implications for interactions with snail plasma factors. AB - The in vitro transformation of the miracidium to the mother sporocyst of Schistosoma margrebowiei was initiated by placing the miracidium in mammalian physiological saline. The transformation occurs in stages: the cilia cease beating; the ciliated plates become detached from the intercellular ridges and underlying muscle layers; the intercellular ridges spread over the body surface eventually forming a new tegument; the sporocyst changes from an ovoid to a tubular shape in about 48 h at room temperature. The surfaces of the miracidium, sporocyst and cercaria of S. margrebowiei display stage-specific carbohydrates on their surfaces as indicated by lectin staining. Ricin120 stains the cilia alone of the miracidium whereas peanut agglutinin stains the larval surface except for the cilia. The intercellular ridges of the miracidium stain with concanavalin A and wheat germ agglutinin, and these lectins stain the entire surface of the mature mother sporocyst. The cercaria is the only larval stage which stains positively with asparagus pea lectin. Bulinus nasutus is incompatible with Schistosoma margrebowiei; the haemolymph of this snail contains an agglutinin which agglutinates a wide variety of mammalian erythrocytes including those of human ABO blood groups. The haemagglutinin titre of B. nasutus plasma is reduced after incubation with miracidia of S. margrebowiei indicating that the agglutinin is absorbed onto the surface of this larval stage but not that of the mother sporocyst or cercaria. The possible roles of agglutinins in host-parasite interactions together with the significance of the differences in the surface carbohydrates of the larval stages are discussed. PMID- 1614740 TI - Relocation of Schistosoma mansoni in the lungs and resistance to reinfection in Rattus rattus. AB - The localization of adult Schistosoma mansoni originating from Guadeloupe (West Indies) was analysed in the natural host Rattus rattus in experimental and natural infections. A transfer of schistosomes from the porto-mesenteric system to the lungs occurs between the 4th and the 20th weeks post-infection, with a peak between 4 and 8 weeks; it should be noted that the worms start laying eggs at 4 weeks post-infection. In both experimentally and naturally infected R. rattus the relocation of schistosomes in the lungs is correlated with the total worm burden. Between 6 and 12 weeks post-infection some adult worms and numerous eggs are trapped in the liver. A high mortality in the worm population coincides with the migration of the parasites from the porto-mesenteric veins to the lungs. In re-infected R. rattus a relationship appears between the presence of schistosomes in the lungs and resistance to reinfection. It is concluded that, as already postulated previously in mice, resistance to re-infection in the natural host R. rattus is at least partly correlated with the hepatic pathology caused by the schistosomes of the primary infection. PMID- 1614741 TI - Praziquantel: physiological evidence for its site(s) of action in magnesium paralysed Schistosoma mansoni. AB - The mechanism whereby praziquantel produces a contraction and subsequent flaccid paralysis (a loss of sensitivity to subsequent stimuli) of Schistosoma mansoni in a medium containing an elevated Mg2+:Ca2+ ratio was investigated. In RPMI, praziquantel produced a concentration-dependent tonic contraction of the parasite with an EC50 of 200 nM. Magnesium inhibited the contraction in such a manner as to convert the tonic contraction to a phasic one without altering the peak force generated. The Mg(2+)-dependent block was non-competitive with praziquantel but was competitive with extracellular Ca2+, ratios of 7.5:1;Mg2+:Ca2+ being needed to inhibit the tonic contraction and to induce flaccid paralysis. Flaccid paralysis was associated with a reduced ability of the parasite to take up 45Ca2+ from the bath compared to parasites that had not entered into flaccid paralysis and flaccid paralysis was reversible. Recovery from flaccid paralysis was accelerated by treatments that are expected to increase Ca2+ uptake by the parasite. At a concentration of 500 nM, praziquantel produced 2 distinct phasic contractions in intact parasites incubated in an elevated [Mg2+] medium but only 1 phasic contraction in parasites lacking their surface tegumental membranes. In zero Ca2+ I-RPMI, 10 microM praziquantel produced a phasic contraction of intact parasites but did not stimulate contraction of detegumented parasites until Ca2+ was reintroduced into the bath. These results indicate that praziquantel interacts with specific Ca(2+)-permeable sites in the tegumental and sarcoplasmic membranes of the parasite and that under these conditions of elevated Mg2+:Ca2+ ratios, these sites become blocked by Mg2+, leading to flaccid paralysis of the parasite. PMID- 1614742 TI - Numerical taxonomy of Trypanozoon based on polymorphisms in a reduced range of enzymes. AB - Numerical analyses of Trypanozoon taxonomy are presented, based on the isoenzyme data of Stevens et al. (1992). The previous study used a reduced range of enzymes compared with earlier work; the analyses indicate the value of this rationalized system. Both recently isolated trypanosome stocks and previously studied populations were included, allowing detailed comparison with earlier studies. Relationships between zymodemes were calculated with an improved similarity coefficient program, using Jaccard's coefficient (1908), and by Nei's method (1972). Dendrograms were constructed from the matrices produced with the group average method. The groupings produced by both numerical methods were in close agreement, and the clusters of related principal zymodemes largely matched the species, subspecies and strain groups proposed by previous workers. Trypanozoon biochemical taxonomy is reviewed and the groupings reinforced by this study are: the mainly East African strain groups, busoga, zambezi, kakumbi, kiboko and sindo; T.b. gambiense and the bouafle strain group from West Africa, and T. evansi; an intermediate bouafle/busoga group was also recognized. PMID- 1614743 TI - Trypanosoma cruzi glutathione-binding proteins: immunogenicity during human and experimental Chagas' disease. AB - Following purification by affinity chromatography, three glutathione-binding proteins (TcGBP) of 45, 30, and 25 kDa were co-purified from Trypanosoma cruzi epimastigotes. Using 1-chloro-2,4 dinitrobenzene as substrate, a glutathione S transferase activity of 70 nmol/min/mg of proteins was detected in the GSH binding fraction. An increased expression of TcGBP and total GST activity was observed upon incubation of parasites with phenobarbital, which is an inducer of GST synthesis. Immunofluorescence and electron microscopic experiments demonstrated that TcGBP were expressed by all developmental stages of the parasite, including infective forms. The expression of these proteins by intracellular dividing amastigotes could be in favour of a potential defensive role of these molecules against host attack. Results obtained by immunoprecipitation of in vitro translation products using anti-TcGBP antisera suggested that these three polypeptides are not glycosylated. In addition, antibodies directed against the TcGBP were found in a high proportion of T. cruzi infected chronic chagasic patients' sera and in sera of chronically infected BALB/c mice. In contrast, acute chagasic patients' sera and acute-phase mouse sera were found to be poorly reactive with these proteins. Our results identify a new class of potential target antigens, which may be essential for the development of T. cruzi in its host. Their protective role in experimental models deserves to be investigated. PMID- 1614744 TI - Genetic variation in Trypanosoma brucei and the epidemiology of sleeping sickness in the Lambwe Valley, Kenya. AB - A contingency table approach was used to explore the influence of location, host species and time on the genetic composition of a Trypanosoma brucei population in Lambwe Valley, Kenya. Significant differences in zymodeme frequencies were noticed over comparatively short geographical distances suggesting that transmission of T. brucei is somewhat localized. A significant association was observed between zymodeme and the mammalian host from which T. brucei was derived. The association was consistent in different localities in Lambwe valley and remained stable for at least 32 months. These observations indicate that zymodemes are adapted to different host species and that genetic exchange has not disrupted host associations over this time-scale. A major change in the composition of the T. brucei population during a sleeping sickness outbreak in 1980 was confirmed. But while new zymodemes emerged, a decline in overall diversity was noted during times of high sleeping sickness incidence. The results can be explained by selection of T. brucei zymodemes for particular transmission cycles. Although it is not necessary to invoke genetic exchange, sex may help T. brucei to adapt to changes in selection pressures. Such a hypothesis helps to explain why T. brucei appears largely clonal in the short term, even though population studies indicate that sex is responsible for much genetic diversity in the long term. It also explains why neighbouring populations of T. brucei are composed of a different range of zymodemes formed from the same alleles. Such a view implies that genetic exchange has an important role in the microevolution of T. brucei populations. PMID- 1614746 TI - Respiratory mechanics in mechanically ventilated newborns: a comparison between passive inflation and occlusion methods. AB - A passive inflation method was described for measuring total respiratory elastance and resistance during mechanical ventilation in adult patients (Rossi et al., J Appl Physiol 58:1849, 1985). We applied this method to preterm and full term mechanically ventilated newborn infants and we compared the results with those obtained by the occlusion method. We performed 37 tests in 16 newborn infants (B.W. 880-4,500 g; G.A. 28-42 weeks), between 1 and 45 days of postnatal age, ventilated with a Servo Ventilator 900C, set in controlled-volume mode. Flow was measured through a pneumotachograph inserted between the endotracheal tube (ETT) and the breathing circuit, tidal volume by integration of flow and airway pressure directly at the airway opening. Flow, volume, and pressure were recorded on an X/Y plotter to obtain pressure-volume (P/V), flow-volume (V/V) loops, and pressure-time curves. Occlusion was performed by using the end-inspiratory and the end-expiratory pause buttons of the ventilator. Analysis of P/V and V/V loops provided respiratory system compliance (Crs, infl.), resistance (Rrs, infl.), and "intrinsic positive end-expiratory pressure" (PEEPi, infl.). These values were compared with Crs, occl., Rrs, occl., and PEEPi, occl. measured by the occlusion method. The measurements were well correlated (Crs, infl./Crs, occl.: r = 0.90; Rrs, infl./Rrs, occl.: r = 0.91; PEEPi, infl./PEEPi, occl.: r = 0.91). Rrs, infl./Rrs, occl. and PEEPi, infl./PEEPi, occl. did not differ significantly. However, Crs, occl. was 15% higher than Crs, infl. (P less than 0.01). The passive inflation method is simple to use and well tolerated in preterm and full term ventilated newborn infants, it provides accurate results, and can be a good alternative to occlusion methods. It requires, however, a constant inflation flow and adaptation to the ventilator. PMID- 1614745 TI - Is there room for another pediatric bronchoscope? PMID- 1614747 TI - Changes in the CA 19-9 antigen and Lewis blood group with pulmonary disease severity in cystic fibrosis. AB - The altered carbohydrate structure of sputum from patients with cystic fibrosis (CF) has been thought to be due to the inflammatory airway response. Carcinoembryonic antigen (CEA) and CA 19-9 detect sialosylated carbohydrates in mucus. The epitope of CA 19-9 is part of the Lewis A (Le(a)) blood group antigen. Serum concentrations of CEA and CA 19-9 were determined by radioimmunoassay in 41 CF patients, aged 6-34 years; 16 were asymptomatic Outpatients, and 25 had been admitted for pulmonary exacerbations. There was no difference in CEA between groups. The CA 19-9 serum concentration was elevated in 90% of patients who had at least one of the two Lewis antigens. The CA 19-9 concentration of Inpatients with exacerbations was 2.7 times that of stable Outpatients (263 +/- 44 versus 99 +/- 13 U/mL; P less than 0.02). CA 19-9 correlated significantly with age (r = 0.35, P less than 0.05), Brasfield score (r = 0.39, P less than 0.015), pulmonary function tests, cough severity (r = 0.50, P less than 0.001) and NIH clinical score (r = 0.57, P less than 0.001). CA 19-9 concentration of Inpatients decreased by 44% from admission to discharge (302 +/- 45 to 169 +/- 39, P less than 0.02). Fourteen of 25 (56%) of the Inpatients were Le(a) positive versus only 3/15 (20%) of Outpatients who had milder lung disease (P less than 0.002). Of the Inpatients, 25% with more advanced lung disease were Le(a+b+), a rare blood group in the normal population, and one not observed in the Outpatients with milder disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614748 TI - Effect of posture on regional ventilation in children. AB - Little information has been published concerning the pattern of regional ventilation in children, yet many differences in lung and chest wall mechanics in childhood, supported by clinical observation, have led to the hypothesis that the pattern of regional ventilation seen in children may not be the same as in adults. Forty-three children and 16 adult volunteers underwent Krypton (Kr) 81m radionuclide ventilation lung scans in the supine and right and left decubitus postures. In children aged 2-10 years mean fractional ventilation to the right lung (VfR) was 46.1%. This fell to 36% when dependent and rose to 56.1% in the uppermost position. Redistribution of ventilation away from the dependent towards the uppermost lung was seen in all children. In children aged 10-18 years VfR was 57.2% (supine), 48.0% (dependent), and 62.9% (uppermost). An identical pattern was seen in children with normal or abnormal pulmonary function tests (peak expiratory flow rate, and FEV1: FVC ratio). In subjects over 18 years of age a different pattern was seen: mean VfR was 52.4% (supine), rising to 53.4% (dependent), and falling to 48.9% (uppermost). Postural redistribution of ventilation, as assessed by Kr81m ventilation imaging, changes late in the second decade of life. This will have clinical consequences in the management of children with unilateral lung disease. PMID- 1614749 TI - New peripherally inserted midline catheter: a better alternative for intravenous antibiotic therapy in patients with cystic fibrosis. AB - A study was performed on outpatients with cystic fibrosis (CF) to evaluate the performance of an over-the-needle peripherally inserted midline catheter for the delivery of 2-week courses of antibiotic therapy. The midline is a 7-inch catheter inserted in the antecubital region with the tip located in the axillary region. It is made of a newly developed biomaterial that softens and expands upon contact with body fluids. The hypotheses for the study were that the midline catheter: 1) is useful for intermediate-length therapies; 2) can prevent multiple 3-day conventional peripheral catheter restarts; 3) can prevent or delay the use of more invasive central devices; 4) is comfortable for patients; and 5) is economical. A total of 41 midlines were inserted in 27 patients with an average age and weight of 22 years and 109 pounds, respectively. Prior to this study implanted ports and primarily conventional short peripheral catheters were used to administer I.V. therapy to these patients; fifty percent of these short peripheral catheters failed within 2.6 days. At 2 weeks of dwell, 80% of the midline catheters placed in these patients were still indwelling. Also, 80% of all midline catheter removals were for non-catheter-related reasons. There were no cases of midline catheter phlebitis. In contrast, the phlebitis rates published for peripherally inserted central catheters (PICCs) and conventional short peripheral catheters at 7 days of dwell are 20% and greater than 51% respectively. The midline catheters were comfortable and well liked by most patients and became more economical than conventional peripheral catheters for therapies lasting approximately 6 days through 1 to 2 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614750 TI - Technique and use of transbronchial biopsy in children and adolescents. AB - Since July 1988, a total of 92 transbronchial biopsies (TBB) have been performed in 18 patients (aged 3-16 years). Twelve patients (67%) were heart-lung transplant (HLT) recipients undergoing surveillance for pulmonary graft rejection and infection. The remainder included immunocompromised patients at risk of opportunistic infections (n = 4), patients with fibrosing alveolitis (n = 1) and a collagen vascular disorder with suspected lung involvement (n = 1). TBB was performed through either a fiberoptic (n = 50) or a rigid (n = 41) bronchoscope, all under general anesthesia. On one occasion a cardiac bioptome was used through an endotracheal stent. The sensitivity of TBB for diagnosing acute and chronic rejection in HLT patients was 88% and 60%, respectively (specificity, 91% and 100%). Definitive diagnoses were made in 4 (67%) of the non-HLT group. Bronchoalveolar lavage (BAL) was performed during each procedure for microbiological and cytological examination. Thirty-four pathogenic organisms including Pseudomonas aeruginosa (16/34), Staphylococcus aureus (8/34), and Candida albicans (5/34) were isolated from BAL culture. Complications included pneumothorax (8%), transient pyrexia (7%), and dyspnea (2%). PMID- 1614751 TI - Optimal electrode location for monitoring the ECG and breathing in neonates. AB - Continuous monitoring of breathing in infants is commonly performed using transthoracic impedance. This method employs skin surface electrodes measuring changes in electrical impedance and relates these changes to respiratory events. Typically, two electrodes on the infant's chest monitor both the ECG and breathing. We have attempted to identify separate electrode locations that give the best signal for breathing and ECG, and a single location that optimizes both of these signals. Thirty-seven infants were studied by placing 12 electrodes on the infant's chest and abdomen, and serially sampling pairwise combinations of electrodes. The optimal signal for breathing was obtained when electrodes spanned the diaphragm. Optimal ECG signal was seen with one electrode at the right mid clavicle and one at the xyphoid. Clinicians should be aware of these locations in order to provide the best signal available. PMID- 1614752 TI - Correcting for the Bernoulli effect in lateral pressure measurements. AB - Measurement of airway pressure is essential in the study of respiratory mechanics, and is usually done via a lateral tap in the conduit (e.g., endotracheal tube, cannula, or mouthpiece) leading into the subject's airway. Such pressure measurements, however, may be severely affected by the Bernoulli effect if the diameter of the conduit is small and the gas flow through it sufficiently high. We present in this note a simple method of assessing whether or not the Bernoulli effect is important in any particular situation. The technique involves comparing the pressure-flow relationships of the conduit obtained both by blowing air through it from one end and sucking air in the reverse direction by applying negative pressure at the same end. If the resistance of the conduit is the same for gas flow in both directions, then half the magnitude of the difference between the two pressure-flow relationships gives the magnitude of the Bernoulli effect pressure. We give results of an experimental situation in which this was the case. We also show that those conditions under which the Bernoulli effect is likely to be a problem are also those under which the velocity profile is likely to be approximately flat, thereby permitting the magnitude of the Bernoulli effect to be easily calculated. PMID- 1614754 TI - Treatment of infants with acute diarrhea: what's recommended and what's practiced. AB - In 1985, the American Academy of Pediatrics (AAP) published a policy statement on the treatment of infants with acute diarrhea complicated by mild to moderate dehydration. To determine how closely physicians in the United States follow the AAP's treatment guidelines, a questionnaire was sent to 457 pediatricians and 360 family practitioners. The questionnaire presented a hypothetical infant with acute diarrhea complicated by mild to moderate dehydration and included questions regarding the number of such patients seen yearly, length of time used to rehydrate the infant, and how formula or solids are introduced following rehydration. Complete responses were received from 53% of pediatricians and 40% of family practitioners. The number of patients with acute diarrhea seen per year did not affect physician's treatment. Pediatricians and family practitioners responded similarly to most questions. Contrary to the AAP's guidelines to rehydrate in 4 to 6 hours, 62% of responding physicians extend the rehydration period to 12 to 24 hours. Also contrary to the AAP's recommendations, 62% of pediatricians and family practitioners use a lactose-free formula. The majority of responding physicians do follow the AAP's treatment guidelines to initiate feedings with diluted formula. Significantly more pediatricians than family practitioners advance to a full-strength formula within 1 day (P = .011). Fewer than 50% of physicians polled started solids within 24 hours as suggested by the AAP. Overall, the findings suggest that very few pediatricians and family practitioners follow all aspects of the AAP's treatment guidelines for infants with acute diarrhea complicated by mild to moderate dehydration. PMID- 1614753 TI - Allergic alveolitis in a 12-year-old boy: treatment with budesonide nebulizing solution. AB - Allergic alveolitis due to bird antigens was diagnosed in a 12-year-old boy. He suffered from cough, dyspnea, easy fatigue, anorexia, and severe weight loss. The diagnosis was verified by a gradual improvement when he was removed from the birds, exacerbation upon re-exposure, and the demonstration of serum precipitating antibodies against bird antigens. The patient recovered completely after a short course of oral prednisolone, treatment with inhaled nebulized budesonide for 3 months, and removal of the birds from his home. PMID- 1614755 TI - Recurrent ovarian cysts in childhood: diagnosis of McCune-Albright syndrome by bone scan. PMID- 1614756 TI - Lichen striatus: simultaneous occurrence in siblings. PMID- 1614757 TI - Retained spur following a rooster attack. PMID- 1614758 TI - Systemic reaction to human growth hormone treated with acute desensitization. PMID- 1614759 TI - Bias and 'overcall' in interpreting chest radiographs in young febrile children. AB - Few studies have examined the diagnostic validity of the examination physician's interpretation of chest radiographs in young febrile children, and none (to our knowledge) the extent to which the "official" (ie, the radiologist's) reading may be biased by access to the examining physician's reading and to other clinical information. The authors studied 287 consecutive chest radiographs obtained in 286 febrile children 3 to 24 months of age without chronic cardiopulmonary disease or known asthma who presented to a children's hospital emergency department between March 1989 and August 1990. The readings by treating pediatricians, official pediatric radiologists, and a "blind" pediatric radiologist were compared. Official radiologists had access to the treating pediatricians' readings and the clinical information provided on the radiography requisition. The blind radiologist knew only that each child was 3 to 24 months of age and febrile, and he was asked to judge the presence or absence of pneumonia. Using the blind radiologist's reading as the "gold standard" for judging validity of the treating physicians' and official radiologists' readings, sensitivity (.677 vs .647), specificity (.828 vs .849), positive predictive value (PPV, .537 vs .571), and kappa index (kappa, .462 vs .475) were quite similar. By contrast, agreement by the treating physicians was considerably higher with the official radiologists' readings as gold standard: sensitivity = .756, specificity = .922, PPV = .795, and kappa = .688. When the treating physician's reading was positive, the official radiologists' positivity rate was much higher than the blind radiologist's (74.4% vs 51.8%, P less than .005), sensitivity was high (.884) but specificity was low (.436), PPV was .663, and kappa was .326.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614760 TI - Causation of kwashiorkor: toward a multifactorial consensus. PMID- 1614761 TI - We have the solution: now what's the problem? PMID- 1614762 TI - Sudden infant death syndrome and sleeping position. PMID- 1614763 TI - American Academy of Pediatrics Committee on Infectious Disease: Acellular pertussis vaccines: recommendations for use as the fourth and fifth doses. PMID- 1614764 TI - American Academy of Pediatrics Committee on Children with Disabilities: American Association for Pediatric Ophthalmology and Strabismus, and American Academy of Ophthalmology: Learning disabilities, dyslexia, and vision. AB - Dyslexia and other related learning disabilities are serious problems. The American Academy of Pediatrics, through its Committee on Children with Disabilities and the Section on Ophthalmology, the American Academy of Ophthalmology, and the American Association for Pediatric Ophthalmology and Strabismus strongly support the need for early diagnosis and educational remediation. There is no known eye or visual cause for dyslexia and learning disabilities, and no effective visual treatment. Multidisciplinary evaluation and management must be based on proven procedures demonstrated by valid research. PMID- 1614765 TI - ECMO and sepsis. PMID- 1614766 TI - ECMO for infection. PMID- 1614767 TI - ECMO and sepsis. If differences could be due to chance alone, are trends worth discussing? PMID- 1614768 TI - Neonatal screening for dependents of active-duty military personnel. PMID- 1614769 TI - Would breast-feeding decrease risks of lead intoxication? PMID- 1614770 TI - The bilirubin debate. PMID- 1614771 TI - The crying of infants with colic: a controlled empirical description. AB - To obtain a controlled empirical description of some of the measurable clinical features of colic in a naturalistic context, 38 infants whose mothers considered crying a problem ("colic") and 38 pair-matched control infants were observed and videotaped at home 10 minutes before and after an evening feed. The parents kept a diary of infant behaviors (including crying and fussing) for 7 days following the visit. Following Wessel et al (Pediatrics. 1954;14:421-434), each "colic" infant was classified according to the number of days per week that crying and fussing duration was greater than 3 h/d. The distribution of infants with colic suggested that there were two subgroups: Wessel's colic infants, with 3 days or more per week of more than 3 hours of crying and fussing per day; and non Wessel's colic infants, with fewer such days. Maternal measures of total daily crying/fussing duration, crying/fussing bout length, and infant temperament and objective analyses of facial activity showed a consistent pattern of differences in which Wessel's colic infants differed from both non-Wessel's colic and control infants, who in turn did not differ from each other. Both colic groups differed from control infants only in the perception of postfeed cries as being more "sick sounding." The results imply that the complaint of colic represents two (or more) groups and that there may be meaningfully distinct colic syndromes. They also provide the first independent empirical support for Wessel and colleagues' clinical distinction between "fussy" and "contented" babies. PMID- 1614772 TI - Back transporting infants from neonatal intensive care units to community hospitals for recovery care: effect on total hospital charges. AB - Many neonates are referred to neonatal intensive care units (NICUs) for specialized care far from their parents' residence. This distance can add to the stress of the parents and reduce the contact of the parents with their newborn. Small studies have found that back transporting these neonates to hospitals closer to their homes is safe and cost-effective. Despite these findings, the reluctance of many insurers to pay for back transports prevents or delays many back transports. Insurers may not consider the findings of the previous studies to be conclusive, given that the comparisons were between small numbers of neonates back transported and neonates who remained in tertiary care, and the potential for differences in severity of illness between the groups is significant. In this study the effect on hospital charges of back transports was examined by comparing the charges for care in community hospitals with what these charges would have been in a tertiary care center. The advantage of this method is that it avoids case-mix differences between the groups and thus minimizes the potential for small-sample bias. Data were collected for all back transports from a NICU to non-tertiary care centers (n = 90) for a 9-month period. We were able to obtain the itemized bills for the care at community hospitals for 42 of these patients. Each bill was recalculated using the charges for the NICU to determine potential for savings. The average charges for recovery care were about $6200 lower at the community hospital than they would have been at the NICU.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614773 TI - On-lap travel: still a problem in motor vehicles. AB - National observational studies indicate that infants who are not restrained in child safety seats (CSSs) in motor vehicles are usually riding on the lap of another occupant. This study was undertaken to determine the conditions under which children travel on-lap. The extent to which injuries would be reduced if these children were restrained in CSSs was also examined. Data were taken from a multihospital monitoring system for pediatric occupant injuries and from the coroner's office in a single urban county (1980 through 1989). One hundred ten children younger than 1 year of age evaluated in the monitored emergency departments after involvement in a crash had been traveling on-lap. On-lap travel did not appear to result from overcrowding. Eighty-eight percent were riding in vehicles with five or fewer occupants; 83% were in the front seat; 58% sustained injury; 22% of those evaluated were hospitalized; and 15% sustained intracranial injury. A 30% reduction in overall injury, a 75% reduction in hospitalization, and a 69% reduction in intracranial injury were projected for those riding on lap, had they been restrained in CSSs. Applying national rates of on-lap travel (16.8%) to National Highway Traffic Safety Administration estimates of the number of infants injured in crashes each year indicates that approximately 2218 of these children would be on the lap of another passenger. Substantial savings in terms of injury and associated costs can be realized if children traveling on-lap were in CSSs. Parent education as well as strict enforcement of CSS laws must be implemented.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614774 TI - A new perspective on the natural history of vesicoureteric reflux. AB - Vesicoureteric reflux is most commonly recognized in girls after urinary tract infection. Increasing recognition of vesicoureteric reflux in neonates, detected after an abnormal prenatal sonogram, shows a marked male predominance: 80% boys. Vesicoureteric reflux in children may be both a congenital abnormality, more common in boys, and an acquired abnormality, more common in girls with voiding dysfunction. PMID- 1614775 TI - A role for prostacyclin in bruising symptomatology. AB - The relationship between bleeding and bruising and the production of prostacyclin and thromboxane was assessed in children who were to have a tonsillectomy and/or an adenoidectomy. Eicosanoids in the blood oozing from the bleeding time incision were measured and correlated with the reported frequency of bruising and epistaxis. A striking association (P = .0003) between prostacyclin production and the frequency of bruising was found; children reporting bleeding at least biweekly had the highest prostacyclin synthesis. Successively lower levels of the prostacyclin metabolite, 6-keto-prostaglandin F1 alpha, were found in children reporting less frequent bruising. Prostacyclin production in bleeding time blood was also correlated inversely with systolic blood pressure and hemoglobin level, although neither of these variables could explain the association between prostacyclin production and bruising. There was no correlation between thromboxane formation, systolic blood pressure, hemoglobin level, age, or bleeding time and the frequency of bruising. The ratio of thromboxane B2 to 6 keto-prostaglandin F1 alpha was correlated inversely with the length of the bleeding time (P = .016). It is concluded that vascular prostacyclin production may have a role in bruising symptomatology. It is suggested that prostacyclin formed at the injured vessel surface collects within the first few seconds after injury inside the tissue space at the site of the bruise and, by influencing the formation of the platelet/fibrin plug and/or the leakage of blood from the vessels, plays a significant role in modifying the development of bruising. PMID- 1614776 TI - Primary hemochromatosis in children: report of three newly diagnosed cases and review of the pediatric literature. AB - Hereditary hemochromatosis was diagnosed in three asymptomatic siblings following the unexpected finding of elevated serum iron concentrations. This diagnosis was confirmed by hepatic biopsy. Repeated phlebotomies resulted in a significant decline of serum iron and ferritin concentrations and a decrease of hepatic iron content. This report and a review of the literature indicate that the diagnosis of hereditary hemochromatosis must be considered more frequently in childhood. Organ dysfunction from iron overload may be minimized in children by the early commencement of regular phlebotomy. PMID- 1614777 TI - Diabetic gastroparesis due to postprandial antral hypomotility in childhood. AB - Nausea, vomiting, chronic abdominal pain, and constipation developed in three children with insulin-dependent diabetes mellitus beginning 1 to 7 years after the onset of diabetes. All three had considerable difficulty in achieving satisfactory glycemic control. All had delayed gastric emptying of solids and postprandial antral hypomotility. Diabetic autonomic neuropathy must be considered in the differential diagnosis of gastrointestinal symptoms even in the young diabetic patient. PMID- 1614778 TI - Umbilical morphology: normal values for neonatal periumbilical skin length. AB - Malformations of the umbilicus are a feature of many dysmorphic syndromes including Rieger syndrome, Robinow syndrome, and Aarskog syndrome. The characteristic umbilical malformation in Rieger syndrome consists of redundant periumbilical skin which extends along the cord for an excessive distance. Although the measurement of umbilical skin length plays an important role in the neonatal diagnosis of Rieger syndrome, normal values for this measurement in healthy neonates have not been established. Umbilical skin length was measured in 104 healthy neonates. The length to which the umbilical skin extended along the cranial aspect of cord (mean 11.53 mm, SD 3.58) was significantly longer than the umbilical skin length along the caudal aspect (mean 8.71 mm, SD 2.89) (P less than .05). Multiple regression analysis revealed a significant association between age and umbilical skin length. Birth weight, length, and gestational age were not significantly associated with umbilical skin length when adjusted for the other three variables. No significant differences in umbilical skin length were observed between male and female groups. The above normal values should aid in the neonatal diagnosis of Rieger syndrome, and furthermore it is recommended that cranial umbilical skin length measurement be included in the examination of the dysmorphic child. PMID- 1614779 TI - Spectrum and frequency of pediatric illness presenting to a general community hospital emergency department. AB - Knowledge of the range of pediatric illness presenting to a general emergency department (ED) is needed to optimize the quality of care delivered there. It was hypothesized that the pediatric population treated at a general ED exhibited a broad range of medical complaints, while differing significantly from children seen in a pediatric ED. General ED records from 1 week each season were reviewed, and patient age, chief complaint, diagnosis, time of arrival, season, and disposition were recorded. Data on 874 patients were analyzed and compared with pediatric ED data. General ED patient age affected chief complaint, diagnosis, and admission rate (9.5% less than or equal to 1 year admitted vs 2.6% greater than 1 year, P less than .001). General ED patients were older (7.9 vs 6.0 years, P less than .001) and admitted less frequently (3.8% vs 11%, P less than .001). Admission rates varied by arrival time only at the general ED, where minor trauma was more common (41% vs 22%, P less than .001). It is concluded that a wide range of pediatric illness is treated in a general ED, supporting the decision to have pediatric emergency physicians on staff, and that significant differences exist in the spectrum and frequency of pediatric illness seen in a general ED and pediatric ED. PMID- 1614780 TI - The changing role and responsibilities of chairmen in clinical academic departments: the transition from autocracy. AB - There is considerable literature dealing with the responsibilities of clinical department chairmen, which primarily emphasizes the importance of developing a sound and facilitating administration. This is dependent on the hiring of appropriate support personnel, developing a representative committee structure, being available to the faculty for their needs, and establishing departmental guidelines, procedures, and policies that apply equally to everyone. Nascent chairmen have an extensive literature available to them concerning academic administration, but a chairman's success is primarily dependent on the possession or development of certain interpersonal skills. Developing a concern and interest in the faculty and staff will come naturally to some and may have to be learned by others. A chairman can attempt to create an excellent esprit de corps by introducing a departmental philosophy that is perceived by the faculty to be supportive. Qualities of the chairman that convey this philosophy are fairness, integrity, compassion, confidentiality, effectiveness, judiciousness, and the willingness to exert considerable effort and time in obtaining recognition and rewards for the faculty. Some of the most difficult tasks for a chairman are (1) the prioritization of his or her responsibilities and activities, (2) representing both the university and the department when their goals appear to conflict, (3) recognizing that an autocratic chairman may administer the department with less difficulty and even appear to have more respect than a democratic chairman, (4) learning to expect less accolades and appreciation from faculty than the clinical chairmen of yesteryear, and (5) resisting the commitment of valuable time to negotiations or battles that cannot be won or to activities that do not benefit the department or the university.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614781 TI - Effect of inclusion of beans in a mixed diet for the treatment of Peruvian children with acute watery diarrhea. AB - A double-masked clinical trial was conducted to assess the effects of inclusion of beans in a mixed diet for young Peruvian children with acute diarrhea. Dietary treatment consisted of either rice, beans, and vegetable oil (group RB, n = 25) or rice, soy-protein isolate, corn syrup solids, and vegetable oil (group RS, n = 21), each given in amounts up to 150 kcal/kg body weight per day immediately following rehydration therapy. The groups were generally similar at the time of admission, and there were no differences in the rates of treatment failure (8% in group RB, 14% in group RS; P = .65). Mean stool outputs were 83 +/- 46 (SD) g/kg body weight in group RB and 71 +/- 43 g/kg body weight in group RS on day 1, and these outputs consistently ranged from 25% to 40% greater in group RB than in group RS (P = .058). By contrast, the median duration of liquid stool excretion was substantially less in group RB than in group RS (60 vs 121 hours, P = .01). The fractional absorption of carbohydrate, fat, and total energy was significantly greater by children in group RS, but there were no differences in net apparent absorption of these nutrients because the children in group RB consumed significantly more of their assigned diet. Children in group RS gained significantly more weight during the whole period of observation (194 g vs 1 g, P = .047), but these differences could be entirely explained by the weight (and presumably fluid) changes on day 1. There were no consistent differences by dietary group in any of the other anthropometric indicators.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614782 TI - Are poor families satisfied with the medical care their children receive? AB - While access to care has been shown to be worse for poor populations, few studies have examined the quality of care received by the poor vs the nonpoor. Furthermore, serious concerns have been raised about the impact of cost containment efforts on the quality of health care for both the poor and nonpoor. The authors examine the interpersonal quality of medical care received by children from poor and nonpoor families by assessing parental satisfaction with physician-patient communication in a telephone survey of a nationally representative sample of households containing 2182 children and adolescents 17 years or younger. The majority of parents were satisfied with many aspects of their interactions with physicians. However, poor families were more likely to be not completely satisfied with the medical care their children received at their last health visit than nonpoor families (27% vs 12%, P less than .001). With regard to specific aspects of the physician-patient communication, poor families were more likely to be not satisfied with the physician's provision of information about the illness (40% vs 21%, P greater than .001); the physician's discussion of examination findings (21% vs 9%, P less than .001); and the opportunity provided by the physician to express their concerns (12% vs 6%, P less than .001). Logistic regression demonstrated that poor patients were approximately twice as likely to be not satisfied with the medical encounter and with various aspects of their communication with the physician. It is concluded that the parents of poor children are less satisfied with their care. Both policy and educational interventions may be needed to address this problem. PMID- 1614783 TI - Referral patterns for children with chronic diseases. AB - A sample of 1377 physicians were surveyed by mailed questionnaire to study to what extent primary care physicians are involved in the long-term care of children with chronic disorders. The sample included all pediatricians practicing in the province of Quebec and a stratified random sample of general practitioners (10% sample in urban areas and 25% sample in rural areas). A response rate of 81% was achieved. Referral patterns were studied for asthma, congenital heart disease, and diabetes. Although pediatricians referred their patients less frequently than general practitioners, referral patterns depended mainly on the clinical condition. "No routine referral" was the most popular management strategy for asthma, whereas for congenital heart disease and diabetes more than 20% of physicians referred their patients for all aspects of care. Rural physicians tended to assume patient care to a greater extent than did urban physicians. Most pediatricians referred patients directly to subspecialists practicing in tertiary care centers, whereas general practitioners often sent patients to pediatricians practicing elsewhere, or to other specialists. These data suggest that the availability of medical resources in the community and accessibility to tertiary care centers also influence physicians' involvement in the long-term care of these children. PMID- 1614784 TI - Television viewing and pediatric hypercholesterolemia. AB - Cholesterol screening for children is recommended currently only for those with a family history of premature coronary heart disease or hyperlipidemia. The authors report on a pediatric-office-based cholesterol screening program where the predictive values of family history indicators were evaluated along with reported television viewing, physical activity, and dietary habits in 1081 children (aged 2 to 20 years, mean 7.4 +/- 3.6 [SD] years). Eight percent of these children had a total cholesterol value of 200 mg/dL or higher; 53% of such children reported watching 2 or more hours of television daily compared with 34% of children with lower cholesterol levels. Multivariate analyses revealed that excessive television viewing was the strongest predictor for a child to have a cholesterol value of 200 mg/dL or higher, with relative risks of 2.2 for 2 to 4 hours of television viewing per day (P less than .01) and 4.8 for children watching more than 4 hours/day, when compared to those watching less than 2 hours/day (P less than .01). In contrast, a positive family history of a high cholesterol level was only modestly associated with an increased probability of having a high cholesterol level (relative risk = 1.6, P less than .05), and a history of premature myocardial infarction in a parent or grandparent was not associated with a child's cholesterol level. Excessive television viewing was found to be associated with certain dietary and physical activity habits and may prove to be a useful, global marker for several life-style factors predisposing children to hypercholesterolemia. PMID- 1614785 TI - Tracking of serum cholesterol levels in a multiracial sample of preschool children. AB - The relation of an initial measurement of serum total cholesterol to subsequent levels over a (mean) 13-month interval was examined in a multiracial (white, Hispanic, American Indian, and black) sample of 1680 one- to four-year-olds. Although the relation of the initial level to the final measurement (r = .54) did not vary by race, sex, relative weight, or changes in relative weight, the association increased with age at the time of the initial measurement (eg, r = .64 among 4-year-olds). Based on the initial and final total cholesterol determinations, the within-person standard deviation was 21 mg/dL and the coefficient of variation was 13%. Although the final total cholesterol level was within 5 mg/dL of the initial level for 18% of the children, the two determinations differed by greater than or equal to 25 mg/dL for about 35% of the children and by greater than or equal to 50 mg/dL for about 8%. Of the 149 children who had an initial cholesterol level greater than or equal to 200 mg/dL, 34% (about five times the expected number) had a follow-up level that was similarly elevated whereas 25% had a subsequent measurement below 170 mg/dL. The results indicate that although an initial cholesterol level in early life is moderately predictive of subsequent levels, it may be difficult to interpret a single total cholesterol determination because of substantial within-person variability. PMID- 1614787 TI - Syringe caps: an aspiration hazard. PMID- 1614786 TI - The occurrence of high levels of acute behavioral distress in children and adolescents undergoing routine venipunctures. AB - While there is no question that children dislike needles, there are very little data available on the occurrence of high levels of distress experienced by children undergoing routine venipunctures. To provide some insight into this problem, trained observers evaluated distress in 223 different children and adolescents undergoing this procedure. An observational distress scale of 1 to 5 was developed; 1 = calm, 2 = timid/nervous, 3 = serious distress, but still under control, 4 = serious distress with loss of control, and 5 = panic. We observed a strong relation between distress and age but not between distress and gender. During the actual venipuncture, half the subjects (113/223) were scored as having high levels of distress (3 or more). Our subjects were also grouped into three age ranges: toddlers; 2 1/2 to 6 years, N = 70; preadolescents; 7 to 12 years, N = 55; and adolescents; 12 years and older, N = 98. The percent of subjects experiencing high levels of distress for each age group were: 83%, 51%, and 28%, respectively. We conclude that for venipunctures: 1) high levels of distress are common, and 2) age and not gender correlates with distress. Other correlations are discussed. Toddlers and pre-adolescents should be the targets for new interventions to reduce distress. PMID- 1614788 TI - Hypercalcemia in association with subcutaneous fat necrosis of the newborn: studies of calcium-regulating hormones. PMID- 1614789 TI - Stroke in an early adolescent with systemic lupus erythematosus and coexistent antiphospholipid antibodies. PMID- 1614790 TI - Decreased thymus size on chest radiography: a sign of pediatric human immunodeficiency virus infection? PMID- 1614791 TI - [Clinico-epidemiological studies of anomalies of the central nervous system in children in evaluation of the effectiveness of their prevention by fetal ultrasonography and genetic monitoring]. AB - A study was made of the prevalence, structure and risk factors of congenital developmental abnormalities (CDAs) of the CNS seen over the recent 17 years in the newborn (217,000 births) and 7845 children of different age, who died during the same period. The stage I work involved a retrospective analysis of the medical documentation up to a broad-scale introduction of ultrasonography of CDAs in the fetus; stage II was concerned, with an analysis of the genetic monitoring after this method was introduced into public health practice, with the coverage of the pregnant amounting to 98%. The recent years have witnessed a stable tendency toward a decrease of both the total incidence of CDAs of the CNS in the newborn and dead children and of the incidence of certain CDAs, namely anencephaly + and hydrocephalus, most accurately diagnosed on ultrasonography. The ratio of pregnancy (the 4th and subsequent ones), pregnancy pathologies (gestosis, infectious diseases), prematurity, intrauterine hypotrophy, previous exposure to ionizing radiation of the future child's mother and father (radiotherapy, industrial hazards, and so forth) are significant risk factors of CDAs of the CNS in the fetus. PMID- 1614792 TI - [Nezelof syndrome in a newborn infant]. PMID- 1614793 TI - [A case of dystonia musculorum deformans in a patient with type I trichorhinophalangeal dysplasia]. PMID- 1614794 TI - [Indicators of lipid metabolism in newborn infants from the Angara region]. PMID- 1614795 TI - [Pulmonary surfactant: its relation to the type of pneumonia and adrenal gland function in children in their first year of life]. PMID- 1614796 TI - [Prenatal risk factors and the status of local defense of the intestines in premature newborn infants]. AB - A randomized study was made to examine certain characteristics of local immunity of the intestine (immunoglobulins in coprofiltrates, microbiocenosis) and the immunoglobulin composition of the milk of mothers to 108 premature breast-fed children of the first month of life. It has been established that toward the end of the second week of life, there was a remarkable decrease in the characteristics of secretory IgA (SIgA) in coprofiltrates of the newborn whose mothers suffered from gestosis (group 2) and in children born to mothers with infectious pathology (group 3) as compared to conventionally healthy premature children (group 1). The group 3 neonates showed a significantly less amount of IgG. According to the examinations made over time, the deficiency of secretory antibodies rose in group 2, declined in group 3, whereas the group 1 children manifested an increase in SIgA. The group 2 and 3 children demonstrated more profound dysbiotic disturbances, characterized by long persistence of opportunistic microorganisms and by the appearance in some cases of pathogenic microorganisms in the intestine. All this requires distinguishing risk groups and carrying out additional preventive and treatment measures in such children. PMID- 1614797 TI - [Clinico-metabolic status of fetuses and newborn infants with fetal macrosomia]. AB - A study was made of the development of large fetuses during pregnancy with regard to the clinical picture, ultrasound screening of the placenta and fetuses, biochemical and immunological monitoring of blood of pregnant women, fetuses and neonates. 172 pregnant women were placed under observation. Of these, large fetuses (the main group) were born in 70 cases, whereas in 102 cases, the fetuses were of medium body weight (the control group). The comparison of the data obtained allows a conclusion that macrosomia gives rise to the acceleration of maturation of the fetal organs and systems, to the intensification of metabolism within the system mother--placenta--fetus. PMID- 1614798 TI - [Processes of absorption and utilization of glucose in newborn infants with intrauterine hypotrophy]. AB - Overall 75 neonates with intrauterine hypotrophy (IH) and 19 healthy children were examined for glucose absorption and utilization according to the glucose tolerance test data. IH neonates were revealed to have and increase of glucose absorption and retardation of its utilization. The high blood glucose concentrations seen 2 hours after the test support functional insufficiency of the pancreas in IH. PMID- 1614799 TI - [Characteristics of central and peripheral hemodynamics in infants with hemolytic disease of newborn]. AB - Overall 82 full-term neonates (52 children with hemolytic disease and 30 healthy neonates) were examined. The general circulation was investigated over time (on days 1, 3.5-7 of life). Use was made of echocardiography and monitor studies of arterial pressure and heart rate; lability of arterial pressure and general peripheral vascular resistance were computed. As a result of the studies and correlations, it has been revealed that neonates with hemolytic disease manifest appreciable disorders of the cardiovascular system, correlating with the disease gravity. Earlier times of the closure of fetal communications were established as were the hyperkinetic type of +cardiac hemodynamics, arterial hypotension accompanied by arterial pressure instability and a decrease of the general peripheral vascular resistance which should be taken into consideration in choosing therapeutic measures. PMID- 1614800 TI - [Liver function in newborn infants with conjugation hyperbilirubinemia after exchange transfusion and hemosorption]. AB - Overall 40 neonates with conjugation jaundice were examined. A study was made over time (after 1 and 5 days) of the content of bilirubin, cholesterol, total protein, cholyl glycine, cholinesterase, and alanine aminotransferase before and after surgical treatment (substitution transfusion and hemoperfusion). It has been established that substitution transfusion inhibits protein synthesizing liver function and raises the content of cholyl glycine. In the authors, opinion, this reduces the bilirubin-binding capacity of albumin and increases hepatocyte membrane permeability. Extracorporeal detoxication makes protein synthesizing liver function return to normal, minimizes the content of cholyl glycine, promoting the growth of the bilirubin-binding capacity of albumin. PMID- 1614801 TI - [Problem of infection in fetuses and newborn infants]. AB - Overall 76 histories of births, case reports of neonates and protocols of autopsies of the dead because of infection were analyzed. It has been established that the overwhelming majority of the children had contracted infection antenatally or during birth, with the ascending pathway of infection being predominant. Attention is drawn to the clinical and postnatal diagnosis with the aid of the screening tests. PMID- 1614802 TI - [The course and outcome of chronic hepatitis B in children]. AB - Overall 98 children aged 1 to 14 years suffering from chronic hepatitis B (CHB) were followed up clinically for 1 to 6 years. CHB was diagnosed on the basis of the clinical and laboratory data. In the majority of the children, the diagnosis was verified by the results of a histological study of liver biopsy specimens. Chronic active hepatitis (CAH), was revealed in 27 children, chronic persistent hepatitis (CPH) in 31. CHB was marked by the presence of HBe-antigenemia in 89 patients (90.8%). The studies have demonstrated that CHB associated with HBe antigenemia runs its course with insignificant clinical manifestations and enzymic exacerbations without jaundice. In the presence of persistent HBs antigenemia, the natural course of CHB (in CAH and CPH) is characterized by seroconversion (from HBeAg to anti-HBe) with a simultaneous decrease and normalization of aminotransferase activity and a reduction of the pathological process activity in the liver (transformation of CAH to CPH). Seroconversion and clinico-biochemical amelioration supervene at different observation periods (after 1-6 years) and do not depend on the initial activity of hepatitis. As the observation period increases, the rate of anti-HBe appearance in the blood rises, amounting to 90% with the observation period exceeding 5 years. The conclusion is made that CHB patients do not need active drug therapy but require long and permanent observation. PMID- 1614803 TI - [Frequency of detection of hepatitis B markers in various chronic diseases in children]. AB - Overall 995 children with different somatic chronic diseases were examined for viral hepatitis B markers demonstration using up-to-date highly sensitive methods (hemagglutination inhibition test, EIA). In the control group (children with acute intestinal infections), HBV-infection markers were discovered in 4.3%. Children with diabetes mellitus (13.1%), chronic renal diseases (18.9%), pulmonary diseases (32.8%), bronchial asthma (33.3%) and hemophilia (85.2%) are attributed to the group at greater risk for HBV infection. As a rule, the rate of HBV-infection markers demonstration in chronic somatic diseases was higher in considerable duration of the underlying illness. The overwhelming majority of the children examined had suffered subclinical forms of HBV-infection as shown by the disease history, whereupon they manifested antibodies against HBV antigens. HBs antigenemia, that persisted for a long time (chronic HBV-infection) was demonstrable far less frequently. The authors provide evidence for the necessity of carrying out a broad-scale screening of HBV-infection markers in the indicated risk groups and vaccination against hepatitis B in children without HBsAG and without immunity to viral hepatitis B. The importance of measures aimed at preventing infections transmitted via blood is emphasized. PMID- 1614804 TI - [Effectiveness of using recombinant interferon alfa2 (reaferon) combined with antioxidants in children with acute hepatitis B]. AB - The authors describe the results of the first experience gained with the use of recombinant alpha 2-interferon in children with acute viral hepatitis B. The drug was administered rectally in combination with antioxidants (tocopherol). The study was carried out by the double blind method with randomization and two control groups (given tocopherol alone or placebo alone). 73 children with acute viral hepatitis B were examined. The therapeutic combination reaferon plus tocopherol was established to favour more rapid elimination of dyspeptic and abdominal phenomena, to shorten the time of the liver and spleen size increase, duration of hyperfermentemia, to provide for an accelerated reduction of HBsAg titers, elimination of HBeAg and seroconversion, to stimulate alpha-interferon production by leukocytes, and to activate the system of mononuclear phagocytes. PMID- 1614806 TI - [Development and morbidity during the first year of life of children breast fed from the first 1.5 hr. after birth]. PMID- 1614805 TI - [Clinical and diagnostic value of complex examination of the bronchoalveolar lavage fluid in nonspecific inflammatory lung diseases in children]. AB - A study was made of the results of cytological, cytochemical (determination of the ratio of ethidium bromide extinction and NTB test) and microbiological studies of bronchoalveolar lavage fluid in 125 children with acute pneumonia and 347 with chronic nonspecific inflammatory pulmonary diseases. It has been revealed that all-round studies permit defining the type and activity of endobronchitis together with the status of the ventilated alveolar tissue. Acute pneumonia is marked by catarrhal process with highly active inflammation of bacterial nature, whereas chronic nonspecific inflammatory diseases by purulent endobronchitis. In localized forms of nonspecific inflammatory pulmonary diseases, streptococci and pneumococci may be regarded as the dominant microflora. PMID- 1614807 TI - [Prospects of reducing perinatal mortality]. AB - The paper is concerned with an analysis of the causes of the perinatal lethality, carried out on a material of 2106 autopsies of fetuses and neonates. The authors describe the structure of the perinatal lethality and the relationship between the character of fetal and neonatal pathology and the mother's health status, pregnancy and delivery. PMID- 1614808 TI - [Effect of eleutherococc extract and dibazole on general and intracellular adaptive reactions in children aged 4-14 years with acute pneumonia]. PMID- 1614809 TI - [Oral administration of a complex immunoglobulin preparation in the treatment of children with acute intestinal infections]. PMID- 1614811 TI - [Experience with the treatment of nonspecific ulcerative colitis in children and adolescents]. PMID- 1614810 TI - [Use of anti-allergic immunoglobulin in children with allergic diseases]. PMID- 1614812 TI - [Pathogenetic substantiation of rational antioxidant treatment of children with kidney diseases]. PMID- 1614813 TI - [Objectives and standards of professional advanced training of pediatricians]. PMID- 1614814 TI - [Principles of conducting immunological rehabilitation of children with secondary immunologic deficiency conditions]. PMID- 1614815 TI - Altered cell volume regulation in ras oncogene expressing NIH fibroblasts. AB - Expression of the Ha-ras oncogene has been reported to stimulate the dimethylamiloride sensitive Na+/H+ exchanger and Na+,K+,2Cl- cotransport, both transport systems which are involved in cell volume regulation. The present study has been performed to test for an influence of ras oncogene expression on cell volume regulation in NIH 3T3 fibroblasts expressing the Ha-ras oncogene (+ ras). As controls served NIH 3T3 fibroblasts not expressing the ras oncogene (-ras). In isotonic extracellular fluid, the cell volume of + ras cells (2.70 +/- 0.08 pl) is significantly greater than the cell volume of -ras cells (2.04 +/- 0.10 pl). Both, + ras and -ras cells exhibit a regulatory cell volume increase in hypertonic extracellular fluid and a regulatory cell volume decrease in hypotonic extracellular fluid. The regulatory cell volume decrease is inhibited by 1 mmol/l quinidine and barium, the regulatory cell volume increase is inhibited in -ras and +ras cells by dimethyl-amiloride (100 mumol/l) and, only in +ras cells, by furosemide (100 mumol/l) and bumetanide (10 mumol/l). In conclusion, expression of the ras oncogene leads to a shift of the set point for cell volume regulation to greater cell volumes, which may contribute to the activation of the Na+/H+ exchanger and Na+,K+,2Cl- cotransport. PMID- 1614816 TI - Slow-to-fast transformation of denervated soleus muscle of the rat, in the presence of an antifibrillatory drug. AB - The myofibrillar changes of rat denervated soleus muscle were studied in the presence and in the absence of an antifibrillatory drug. After bilateral sciaticotomy, a concentrated solution of procainamide hydrochloride was steadily released, by way of a miniosmotic pump, in the space between the soleus and the gastrocnemius muscles of one leg. Fibrillation activity of soleus muscles was checked electromyografically at 3- to 5-day intervals. On the 21st day following denervation the muscles were excised, stained for adenosine triphosphatase activity and analysed for myosin heavy chain (MHC) isoforms. In the denervated procainamide-treated muscles fibrillation was consistently (-75% on average) depressed in comparison to the contralateral denervated muscles. Type 1 (slow) fibres and MHC isoform were also significantly reduced, to the advantage of type 2A (fast) fibres and MHC isoform. The results support the view that denervation inactivity, like other kinds of muscle inactivity, favours the expression of fast type myofibrillar isoforms, and that this effect is counteracted, at least partially, by the spontaneous activity of the denervated muscle. PMID- 1614817 TI - Voltage-dependent currents in isolated cells of the turtle retinal pigment epithelium. AB - The electrophysiological properties of isolated turtle retinal pigment epithelial cells (RPE cells) were investigated using the whole-cell patch-clamp technique. Most RPE cells exhibited a voltage-dependent outward current activated by depolarization beyond about -43 mV that inactivated during a 500-ms voltage step. Tail current measurements indicated that the conductance underlying this current was potassium selective. This current inactivated with prolonged depolarization and was abolished or reduced by extracellular quinidine, barium, tetraethylammonium (TEA) and 4-aminopyridine (4-AP). Steady-state inactivation of the voltage-dependent outward current revealed a time-independent outwardly rectifying current/voltage relationship in many cells. In addition, many cells had an outward current that activated slowly upon depolarization beyond about +40 mV and appeared to reverse near 0 mV in both 3 mM KCl and 30 mM KCl external solutions. This current was often observed in the presence of potassium channel blockers. Hyperpolarizing pulses commonly evoked inward currents that activated slowly and did not inactivate. These currents were commonly observed when fluoride was absent from the pipette, and only occasionally when fluoride was the major pipette anion. Tail current measurements indicated that this current was somewhat anion selective. These currents may play important roles in the homeostatic and phagocytic functions of RPE cells in their interactions with the neural retina. PMID- 1614818 TI - Ca-dependent K channels in smooth muscle cells permeabilized by beta-escin recorded using the cell-attached patch-clamp technique. AB - Using the cell-attached patch-clamp technique, the activity of single, Ca dependent K channels was recorded in single smooth muscle cells permeabilized by beta-escin. The conductance and the relationship between the open probability of the channels and pCa recorded in permeabilized cells were very similar to those obtained in excised inside-out patches. At pCa 7, application of 30 microM acetylcholine (ACh) or 0.1 microM substance P (SP) together with 1 mM guanosine 5'-trisphosphate to permeabilized cells elicited transient bursts of channel openings similar to those which occur in intact cells. Transient activation was also observed when 2-30 microM inositol trisphosphate (IP3) was applied to permeabilized cells. This single channel activity was inhibited by pretreatment with low-molecular-weight heparin at 50-100 micrograms/ml. Channel activity at pCa 7.0 was greatly enhanced by 200 microM cyclic adenosine monophosphate. These results provide direct evidence that single Ca-dependent K channel activity is regulated by the transmitters ACh and SP, as well as a second messenger, IP3, via the release of intracellular Ca from intracellular sites which are blocked by heparin. This novel approach is valuable in elucidating second messenger mechanisms involved in the regulation of single channel activity by transmitters and autocoids, since permeabilization by beta-escin preserves the entire system of receptor-operated signal transduction and allows intracellular application of second messengers at fixed concentrations. PMID- 1614820 TI - Desensitization of acetylcholine receptors in BC3H-1 cells. AB - We studied desensitization of nicotinic acetylcholine (ACh) receptor channels in the clonal BC3H-1 cell line. We measured the current response to rapid perfusion of outside-out patches with 1 microM to 5 mM ACh, carbamylcholine and suberyldicholine. After binding to the receptors and opening the ion channels, all agonists induce a rapid, concentration-dependent decay of channel activity. The time constant of the current decay ranged from several seconds at low agonist concentrations to about 50 ms at saturating concentrations. The decay rate at saturating concentrations was independent of voltage. The ratio of steady-state to peak current ranged from 0.5 at low agonist concentrations to 0.02 or less at high concentrations. The rate of recovery from desensitization after removal of agonist was also measured. For ACh, the recovery time constant was 320 ms; recovery from desensitization by carbamylcholine was twice as fast. A linear kinetic results. The data are consistent with a cyclic model, although, it is not possible to uniquely determine all of the rate constants in this scheme. The results are compared with competitive binding and single channel studies of desensitization in BC3H-1 cells. PMID- 1614819 TI - Inactivation of the Ba2+ current in dissociated Helix neurons: voltage dependence and the role of phosphorylation. AB - The rate of inactivation of the voltage-dependent Ba2+ current in dissociated neurons from the snail Helix aspersa was found to be modulated by phosphorylation. Conditions were chosen such that the most likely mechanism of inactivation of the Ba2+ current was a voltage-dependent/calcium-independent inactivation process. If adenosine-triphosphate (ATP) was not included in the patch electrode filling solution, or if alkaline phosphatase was added, the Ba2+ current rapidly ran down and the rate of inactivation greatly increased with time. Dialysis with either ATP gamma S or the phosphatase inhibitor okadaic acid (OA) either enhanced the amplitude or greatly reduced the rate of run-down of the Ba2+ current (depending upon the presence of ATP), as well as reducing the rate of inactivation. However, dialysis with either the catalytic subunit of the cyclic-adenosine-mono-phosphate-dependent protein kinase (cAMP-PK), a synthetic peptide inhibitor of this enzyme, or staurosporine (a potent inhibitor of protein kinase C), did not have any significant effect on the amplitude or kinetics of the Ba2+ current. Surprisingly, dialysis with a peptide inhibitor (CKIP) of the Ca2+/calmodulin-dependent protein kinase II (Ca(2+)-CaM-PK) significantly reduced the rate of inactivation of this current. These results suggest that phosphorylation may exert its effect by modulating the gating properties of the Ca2+ channels. PMID- 1614821 TI - Neurotransmitters inhibit the omega-conotoxin-sensitive component of Ca current in neuroblastoma x glioma hybrid (NG 108-15) cells, not the nifedipine-sensitive component. AB - Voltage-dependent calcium currents (ICa) in NG 108-15 cells consisted of three pharmacologically distinct components: a transient low-voltage-activated (LVA) current, sensitive to Ni2+; a high-voltage-activated (HVA) current sensitive to the dihydropyridine antagonist, nifedipine and a HVA current sensitive to omega conotoxin GVIA (CgTx). The voltage sensitivities and decay kinetics of the two HVA currents were indistinguishable. The neurotransmitters acetylcholine (ACh) and noradrenaline inhibited ICa. This inhibition was not occluded by Ni2+ or nifedipine, but was abolished by CgTx. It is therefore concluded that the neurotransmitter-sensitive component of ICa is restricted to that component of HVA current inhibitable by omega-conotoxin. PMID- 1614823 TI - Cortical temperature and EEG slow-wave activity in the rat: analysis of vigilance state related changes. AB - Vigilance states, cortical temperature (TCRT), and electroencephalograph (EEG) slow-wave-activity (SWA, mean power density in the 0.75-4.0 Hz range) of ten rats were recorded continuously during a baseline day, and two recovery days (Recovery 1 and 2) after 24 h of sleep deprivation (SD). The short term changes of TCRT were analysed within episodes of nonrapid eye movement sleep (NREMS), REM sleep (REMS) and waking (W), and at transitions between vigilance states. SWA was analysed within NREMS episodes and at W to NREMS (WN) transitions. TCRT increased during episodes of W and REMS, and decreased during NREMS episodes. These changes were a function of episode duration, and, for W and NREMS, of TCRT at episode onset. In Recovery 1 the increase in TCRT at NREMS to REMS (NR) and NREMS to W (NW) transitions tended to be attenuated. SWA within NREMS episodes was enhanced after SD. Over all experimental days, the increase of SWA and the decrease of TCRT in NREMS episodes were not correlated. It is concluded that during recovery from SD the changes in TCRT at state transitions were little affected. The lack of a relationship between changes in TCRT and SWA indicates that separate mechanisms underlie the regulation of brain temperature and sleep intensity. PMID- 1614822 TI - Na(+)-Ca2+ exchange in the isolated cochlear outer hair cells of the guinea-pig studied by fluorescence image microscopy. AB - The outer hair cell isolated from the guinea-pig was superfused in vitro and the cytosolic calcium concentration ([Ca2+]i) and sodium concentration ([Na+]i) were measured using fluorescence indicators. Under the resting condition, [Ca2+]i and [Na+]i were 91 +/- 9 nM (n = 51) and 110 +/- 5 mM (n = 12), respectively. Removal of external Na+ by replacing with N-methyl-D-glucamine (NMDG+) increased [Ca2+]i by 270 +/- 79% (n = 27) and decreased [Na+]i by 23 +/- 4 mM (n = 6). Both changes in [Ca2+]i and [Na+]i were totally reversible on returning external Na+ to the initial value and were inhibited by addition of 0.1 mM La3+ or 100 microM amiloride 5-(N,N-dimethyl) hydrochloride. Elevation of external Ca2+ ions to 20 mM reversibly decreased [Na+]i by 8 +/- 6 mM (n = 5). Moreover, the chelation of the intracellular Ca2+ with 1,2-bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA) exerted an inhibitory action on the NMDG(+)-induced reduction in [Na+]i. Exposure to 5 mM NaCN for 2 min significantly and reversibly increased [Ca2+]i by 290 +/- 37% (n = 5), but did not affect the [Ca2+]i elevation induced by the NMDG+ solution. The rise in [Ca2+]i induced by the NMDG+ solution was not enhanced by ouabain pretreatment. Addition of ouabain did not alter the [Na+]i. The present results are best explained by the presence of an Na(+)-Ca2+ exchanger in cell membrane and indicate that the activity of Na+/K+ pump is poor in outer hair cells. PMID- 1614824 TI - Endothelin-1 blunts transepithelial transport and differentiation of Madin-Darby canine kidney cells. AB - We investigated the effects of endothelin-1 (ET-1) on Madin-Darby canine kidney (MDCK) cells, a cell line originating from the renal collecting duct. The activity of transepithelial transport was assessed as the rate of dome formation in monolayers grown on solid support. The pH value of the dome fluid (dome pH) was measured by means of pH-selective microelectrodes. Differentiation of monolayer cells was estimated as the peanut-lectin(PNA)-binding capacity of the apical membrane. Confluent monolayers were incubated for 12-72 h in serum-free medium at various concentrations of ET-1. Exposure to 1 nmol/l ET-1 reduced dome formation by a maximum of 41 +/- 8% (n = 4; P less than 0.02) after 24 h. ET-1 (10 nmol/l; 24 h) decreased dome pH from 7.52 +/- 0.02 (n = 53) to 7.36 +/- 0.03 (n = 51; P less than 0.02). Apical application of amiloride (1 mmol/l) reduced dome pH in both ET-1-treated and non-treated domes to essentially the same level, 7.25 +/- 0.03 (n = 19) and 7.23 +/- 0.03 (n = 17) respectively. ET-1 (10 nmol/l; 24 h) reduced PNA-binding capacity by 19 +/- 3% (n = 5; P less than 0.02). Moreover, ET-1 prevented the increase in PNA binding (+ 53 +/- 7%; n = 5) induced by 0.1 mumol/l aldosterone. We conclude that ET-1 inhibits transepithelial transport and PNA binding via inhibition of apical Na+/H+ exchange, thus antagonizing aldosterone action in MDCK cells. PMID- 1614826 TI - Regulation of oxygen radical production of human polymorphonuclear leukocytes by adenosine: the role of calcium. AB - In polymorphonuclear leukocytes (PMNL) adenosine is a potent inhibitor of stimulus/response coupling, as demonstrated by its adverse action on phagocytosis, degranulation and oxygen radical production. Because this nucleoside can reduce several cell functions by counteracting intracellular calcium ions (Ca2+), the present study investigates the effect of adenosine on oxygen radical production in human PMNL stimulated by N-formylmethionyl-leucyl phenylalanine (fMet-Leu-Phe), zymosan-activated serum (ZAS) and ionophore A 23187 in a Ca(2+)-dependent manner, and stimulated by phorbol myristate acetate (PMA) and latex in a Ca(2+)-independent manner. The results demonstrate that all the Ca(2+)-dependent stimuli were concentration-dependently inhibited by adenosine. In contrast, leukocyte stimulation by the Ca(2+)-independent activator PMA was not affected by adenosine. Surprisingly, radical formation stimulated by latex beads was concentration-dependently reduced by adenosine. When intracellular Ca2+ was modified by the ionophore clamping technique or the Ca(2+)-buffering capacity of quin-2, latex-induced radical formation could be separated into two parts, one showing Ca(2+)-dependent and the other Ca(2+)-independent activation. In the presence of intracellular Ca2+, adenosine exerted a strong inhibition on the latex-induced cell activation but failed to inhibit in the Ca(2+)-depleted state. In order to elucidate a direct reduction of Ca2+ as the underlying mechanism of adenosine-mediated inhibition, intracellular Ca2+ was measured in PMNL by quin-2 fluorescence. When PMNL were activated by latex, fMet-Leu-Phe and ionophore A 23187, adenosine significantly reduced the stimulated rise in intracellular Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614825 TI - AlF4- and vanadate stimulate chloride secretion in rabbit colon by a Ca(2+) dependent mechanism. AB - Stripped rabbit descending colon mucosae were studied in vitro in modified Ussing chambers to determine the effects of AlF4- and vanadate on Cl- transport. Serosal additions of AlF4- and vanadate increase short circuit current (Isc) and tissue conductance, while luminal addition of the agents is ineffective. Addition of aluminium potentiates the effect of NaF on Isc. AlF4- and vanadate increase serosal-to-mucosal flux of 36Cl without affecting mucosal-to-serosal flux. The effects of these agents on Isc are markedly inhibited by serosal addition of bumetanide and depend on the presence of Na+ in the serosal bathing solution. The effects of AlF4- and vanadate on Isc are dependent on the presence of Ca2+ in the bathing solution, and are completely inhibited by indomethacin, but the effect of forskolin is not affected by the removal of Ca2+ from the bathing solution and the addition of indomethacin. AlF4- and vanadate significantly increase the level of inositol phosphate metabolites. The results indicate that AlF4- and vanadate increase Cl- secretion in the rabbit colon via an increase in prostaglandin synthesis which is mediated by the increase of intracellular Ca2+ concentrations. PMID- 1614827 TI - A loudspeaker-driven system for rapid and multiple solution exchanges in patch clamp experiments. AB - A new and inexpensive system allowing rapid and synchronized changes of solutions around a membrane patch or a cell under voltage-clamp conditions is described. Four plastic capillary tubings (OD 640 microns; ID 430 microns) were glued together horizontally and attached to a coil of a commercially available loudspeaker. Servo-control of the position of the coil allowed the mouth of any of the capillaries to be positioned near the pipette tip within 6 ms. A high flow speed of the test solution was crucial to achieve rapid solution exchange. At a flow speed of 5 cm/s, complete exchange of the external environment of a frog ventricular cell was achieved within 20-30 ms. The time course of solution change was found to be 3-5 times faster at the tip of an open patch pipette. To preserve the physical integrity of the cell, the cell was usually perfused by a control capillary at a slow velocity (0.2-0.4 cm/s) and test solutions flowing out of adjacent capillaries at high velocity (4-5 cm/s) were applied to the cell only for short periods. Determination of the three-dimensional contamination profile around the mouth of the control capillary allowed the optimal conditions for the use of the system to be established and possible sources of contamination to be avoided between adjacent capillaries with unmatched flow speeds. Successive and multiple changes in external solutions could be easily synchronized with voltage clamp depolarizations to examine the time course of the effect of drugs on voltage-operated ion channels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614828 TI - Endogenous and exogenous agonist-induced changes in the coupling between [Ca2+]i and force in rat resistance arteries. AB - The relationship between isometric tension and free cytoplasmic calcium, [Ca2+]i, was investigated in rat isolated resistance arteries using fura-2. Depolarisation with 125 mM K+ induced a tonic contraction, while [Ca2+]i increased transiently but stabilised above resting [Ca2+]i. Furthermore, the tension/[Ca2+]i ratio was lower during activation with 125 mM K+ if the effect of endogenous noradrenaline (NA) was inhibited. Concentration/response curves with NA and K+ indicated that NA increased the sensitivity to [Ca2+]i. Calcium concentration/response curves in the presence of 10 microM NA or 125 mM K+ showed that NA could induce force at or below resting [Ca2+]i, while for any given bath calcium concentration, [Ca2+]i was similar in the presence of NA or K+. Addition of NA or vasopressin (AVP) to vessels depolarised with 125 mM K+ caused force development but no increase in [Ca2+]i, suggesting that agonists increase the efficacy of [Ca2+]i. However, during activation with AVP the efficacy of [Ca2+]i decreased time-dependently. The results suggest that in resistance arteries [Ca2+]i plays a crucial role in excitation-contraction coupling, but the tension/[Ca2+]i relationship can be modified by exogenous and endogenous agonists. PMID- 1614829 TI - Phosphate transport in isolated rat inner medullary collecting duct. AB - Phosphate transport by the inner medullary collecting duct of normal rats was studied using an in vitro microperfusion technique. Net (Jnet), lumen-to-bath (Jlb) and bath-to-lumen (Jbl) phosphate fluxes were measured using 32PO4 as tracer, in the absence of net water absorption. A net absorption of phosphate (22.3 +/- 3.3 pmol cm-2 s-1) was observed by direct determination, and was similar to the difference between the Jlb and Jbl (57.7 +/- 8.2 and 32.2 +/- 1.5 pmol cm-2 s-1 respectively). The addition of amiloride (10 microM) to the perfusate did not change the Jlb of phosphate but blocked the efflux of sodium. Also, the withdrawal of sodium from the bath and perfusion solution did not change the Jlb of phosphate. In parallel, the addition of ouabain (10 mM) to the bath fluid decreased the Jlb of sodium more (37%) than the Jlb of phosphate (12%) and did not change the Jbl of phosphate. The addition of arsenate (10 microM) to the perfusate both in the presence and in the absence of sodium caused a decrease in Jlb, but Jbl remained unchanged, and parathyroid hormone (10 U) added to the bath did not change the Jlb. The increase in pH of the bath and perfusion fluid was associated with an increase in the Jlb of phosphate, and the decrease in pH was similarly followed by a decrease in phosphate efflux. The Jbl did not change with the pH alterations. These data demonstrate that a net phosphate absorption takes place in rat inner medullary collecting duct perfused in vitro and that this transport appears to be independent of sodium absorption and the action of parathyroid hormone. Moreover, a decrease in luminal and bath pH induces a decrease in phosphate efflux. PMID- 1614830 TI - Mechanism of Cl- transport in eel intestinal brush-border membrane vesicles. AB - Cl- transport was studied in a preparation of brush-border membrane vesicles (BBMV) from seawater eel intestine. 36Cl- uptake appeared to be stimulated by a positive inside membrane diffusion potential generated (a) by a concentration gradient of salts, the cations of which are more permeable than the anions, (b) by a K+ diffusion potential obtained by imposing a K+ concentration gradient (Cout greater than Cin) in the presence of valinomycin, (c) an inwardly directed H+ ion concentration gradient. The membrane-potential-driven Cl- transport was inhibited by 1 mM 5-nitro-2-(4-phenylpropyl-amino)-benzoic acid. Arachidonic acid also inhibited Cl- uptake in eel intestinal BBMV, but the effect appeared to be unspecific, as the unsaturated fatty acid also affected the Na+ dependent D glucose uptake. The effect of arachidonic acid was reversed in the presence of bovine serum albumin. Cl- influx was the same in the presence of inwardly directed gradients of Li+, Na+ or K+, arguing against the presence of Na(+)-Cl-, as well as K(+)-Cl- cotransport. The absence of a significant contribution of the Na(+)-K(+)-2Cl- cotransport mechanism to the Cl- uptake in seawater eel intestinal BBMV was indicated from the observations that Cl- uptake was not stimulated by the simultaneous presence of inwardly directed Na+ and K+ gradients, and that it was nearly insensitive to 1 mM bumetanide in the presence of extravesicular Na+ and K+. Furthermore, no evidence for the dependence of Cl- uptake on the Na+ gradient was obtained under a short-circuited membrane diffusion potential, i.e. in the presence of equilibrated K+ and valinomycin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614831 TI - Role of Na+/Ca2+ exchange in transcellular Ca2+ transport across primary cultures of rabbit kidney collecting system. AB - Cells from connecting tubule and cortical collecting duct of rabbit kidney were isolated by immunodissection with mAb R2G9 and cultured on permeable filters. Confluent monolayers developed an amiloride-sensitive transepithelial potential difference of -50 +/- 1 mV (lumen negative) and a transepithelial resistance of 507 +/- 18 omega cm2. Transepithelial Ca2+ transport increased dose-dependently with apical [Ca2+] and, in solutions containing 1 mM Ca2+, the active transcellular Ca2+ transport rate was 92 +/- 2 nmol h-1 cm-2. Transcellular Ca2+ transport was dependent on basolateral Na+ (Nab+). Isoosmotic substitution of Nab+ for N-methylglucamine resulted in a concentration-dependent decrease in Ca2+ absorption, with maximal inhibition of 67 +/- 5%. A Hill plot of the Na(+) dependence yielded a coefficient of 1.9 +/- 0.4, indicating more than one Na+ site on a Na(+)-dependent Ca2+ transport system. In addition, the absence of Cab2+ resulted in a significant increase in Ca2+ transport both in the presence and absence of Nab+. Added basolaterally, ouabain (0.1 mM) inhibited Ca2+ transport to the same extent as did Na(+)-free solutions, while bepridil (0.1 mM), an inhibitor of Na+/Ca2+ exchange, reduced Ca2+ transport by 32 +/- 6%. Methoxyverapamil, felodipine, flunarizine and diltiazem (10 microM) were without effect. Depolarisation of the basolateral membrane, by raising [K+]b to 60 mM, significantly decreased transcellular Ca2+ transport, which is indicative of electrogenic Na+/Ca2+ exchange. In conclusion, active Ca2+ transport in the collecting system of rabbit kidney is largely driven by basolateral Na+/Ca2+ exchange. However, a residual Ca2+ absorption of about 30% was always observed, suggesting that other Ca2+ transport mechanisms, presumably a Ca(2+)-ATPase, participate as well. PMID- 1614832 TI - A fast perfusion system for single cell physiology optimized for microscopes with water immersion objectives. AB - A perfusion system was constructed which allows the fast application of different solutes underneath a water immersion objective. The perfusion system is mounted into the immersion objective by milling a slot into the frontal metal plate of the lens holder. It consists of a five-channel pipette fixed to the objective and solution reservoirs gated by computer controlled magnetic valves. Up to five different solutions can be applied to the specimen under study. The solution between objective and specimen is completely exchanged after 1-2 s as determined from fluorescence measurements. This arrangement is optimized for [Ca2+] measurements with a fluorescence measurement system in tissue slices, where upright microscopes are required. It offers the advantage of saving a micromanipulator for the perfusion pipette and facilitates a fast, reproducible and precise positioning of the perfusion system. PMID- 1614833 TI - A comparison of isometric force, maximum power and isometric heat rate as a function of sarcomere length in mouse skeletal muscle. AB - The isometric force, maximum power and isometric heat rate have been measured at different sarcomere lengths (SL) between 1.40 and 3.63 microns in two types of mouse muscle, soleus and omohyoideus, at 25 degrees C. The SL force relationship is different in the two muscles. At a SL above optimum filament overlap, 2.44 microns in omohyoideus muscles, maximum power declined while isometric force remained high. In soleus muscles this occurred above a SL of 2.33 microns. In parallel experiments, the isometric heat rate declined linearly with increasing SL above 2.33 microns in soleus muscles, while isometric force remained closer to its maximum. At short SL, between 2.33-1.75 microns in soleus and 2.44-2.15 microns in omohyoideus, maximum power remained at or near its maximum value as did heat rate (soleus) while isometric force fell. In both muscles at SL greater than optimum for force development maximum power output (unlike force) is proportional to filament overlap. The variation in heat rate over this SL range can be described as the sum of constant rate and a rate proportional to filament overlap. These observations are compatible with the idea that maximum power and heat rate are less affected by non-uniformities in SL than is force. PMID- 1614834 TI - Bicarbonate-dependent changes of intracellular sodium and pH in identified leech glial cells. AB - A new triple-barrelled ion-sensitive microelectrode was used to investigate the importance of bicarbonate for the regulation of intracellular Na+ and pH (Nai and pHi, respectively) of neuropile glial cells in the central nervous system of the leech Hirudo medicinalis. Addition of CO2/HCO3- produced an increase of the Nai activity and an intracellular alkalinization, indicating bicarbonate accumulation in the glial cells. Changes of external pH (from 7.4 to 7.0 and 7.8) produced large and rapid shifts of pHi and Nai and of the membrane potential in the presence, but not in the absence, of bicarbonate. Thus, acid/base transport and Na+ movements across the glial membrane into and out of the cells were accelerated severalfold in CO2/HCO3(-)-buffered saline as compared to a CO2/HCO3( )-free, HEPES-buffered saline. The results suggest that the electrogenic, reversible, cotransport of Na+ and HCO3- in the glial cell membrane [3,9] can produce significant changes in intraglial pH and Na activity, and can carry a significant fraction of the total Na+ flux across the cell membrane. PMID- 1614835 TI - Comparison of two types of Na+ currents with low-voltage-activated T-type Ca2+ current in newborn rat dorsal root ganglia. AB - Na+ currents and the low-voltage-activated T-type Ca2+ current (T-ICa) were recorded from neurons of rat dorsal root ganglia under similar ionic environments using the whole-cell patch-clamp technique. Two types of Na+ currents were identified on the basis of their sensitivity to tetrodotoxin (TTX) and channel kinetics. One type was blocked by 1 nM TTX and had a faster activation and inactivation time courses (F-INa), while the other type was insensitive to 100 microM TTX and had a much slower channel kinetics (S-INa). Activation thresholds were -60, -40 and -70 mV for F-INa, S-INa and T-ICa, respectively. Peak amplitudes were obtained in respective current/voltage curves at -30 mV (F-INa), 0 mV (S-INa) and -50 mV (T-ICa). The time to peak and the decay time constant measured at potential levels giving peak amplitudes were 0.5 and 1.5 ms for F INa, 1.4 and 2.9 ms for S-INa and 8.1 and 17 ms for T-ICa, respectively. Cd2+ in a concentration of 50 microM totally blocked T-ICa, whereas it had no effect on either type of Na+ current. T-INa was found in 18 out of 25 cells which possessed F-INs, whereas it was found in only 2 cells among 15 which lacked F-INa. These three types of inward currents having different kinetic and pharmacological properties may mediate diverse functional roles in processing sensory signals. PMID- 1614836 TI - Intracellular ion imaging using fluorescent dyes: artefacts and limits to resolution. AB - Development of highly efficient fluorescent ratio indicators has made imaging of ion concentrations within individual cells possible (Grynkiewicz et al. 1985; Tsien and Poenie 1986). Ion imaging is a complex technique and is therefore prone to artefacts. In this paper we investigate the limits of the technique and its potential pitfalls. The spatial resolution of an imaging system is determined for different cell geometries. We describe a technique to increase the time resolution of existing systems by using a single excitation wavelength to measure changes in ion concentration. We demonstrate examples of potential artefacts arising from hardware limitations, image processing and fundamental optics. Methods for recognition and minimization of these problems are discussed. PMID- 1614837 TI - Design and use of an "optrode" for optical recordings of cardiac action potentials. AB - An optical method was used to measure action potentials from frog ventricle, in vitro, under normal physiological conditions with 0.5-1 mM Ca2+ Ringer's solution. The approach presented in this paper involves a portable fluorimeter coupled to a multimode optical fiber running into a glass pipette ("optrode") to carry both excitation light to and fluorescence from the ventricle stained with the voltage sensitive dye di-4-ANEPPS. A suction technique was used to stabilize the optrode-tissue interface, significantly reducing motion artifacts from the beating ventricle. The typical fractional change in fluorescence intensity for an action potential was -9%. The optical recordings faithfully reproduced membrane action potentials as measured with microelectrode recordings. To confirm further the validity of our method we studied the effect of an increasing stimulation rate on the optical action potential. The amplitude of the action potential did not increase, and the change in action potential duration was similar to published results obtained with microelectrode recordings, suggesting that our optical action potentials are relatively free of motion artifacts. Finally, our optical recordings suggest that during anodal and cathodal point stimulation, the time course of membrane potential differs from that predicted simply by a passive cable model. PMID- 1614838 TI - A method for exceptionally low noise single channel recordings. AB - We present a method whereby, with integrating electronics, quartz patch electrodes and a novel use of silicone oil, background noise levels as low as .083 pA RMS in a 5 kHz bandwidth (4-pole Butterworth filter) have been achieved in single channel patch clamp recordings. These approaches result in much higher signal to noise ratios for single channel recording than have previously been reported and should allow many investigators to significantly reduce noise at a constant bandwidth or to increase their recording bandwidths by several kHz. PMID- 1614839 TI - [Real forensic difficulties in dental treatment]. PMID- 1614840 TI - Module II.1. Fetal effects of maternal alcohol and drug use. PMID- 1614841 TI - Module II.2. Impaired practice by health professionals. PMID- 1614842 TI - Module II.3. Addictions: nursing diagnosis and treatment. PMID- 1614843 TI - Module II.4. Nursing care in acute intoxication. PMID- 1614844 TI - Module II.5. Nursing care in withdrawal. PMID- 1614845 TI - Module II.6. Drug misuse and dependence in the elderly. PMID- 1614846 TI - Module II.7. Drug and alcohol problems in special populations. PMID- 1614847 TI - Module II.8. Nursing care of drug and alcohol problems in special populations. PMID- 1614848 TI - State-approved schools of nursing R.N. 1992. PMID- 1614850 TI - Binding of TFIIIA to derivatives of 5S RNA containing sequence substitutions or deletions defines a minimal TFIIIA binding site. AB - The repetitive zinc finger domain of transcription factor IIIA binds 5S DNA and 5S RNA with similar affinity. Site directed mutagenesis of the Xenopus borealis somatic 5S RNA gene has been used to produce a series of derivatives of 5S RNA containing local sequence substitutions or sequence deletions. Gel mobility shift analyses of the binding of TFIIIA to these altered 5S RNAs revealed that all three of the helical stems of the 5S RNA secondary structure are required for binding. TFIIIA was observed to bind with normal affinity to RNAs lacking 12 nucleotides at either the loop c or loop e/helix V regions of 5S RNA, as well as to a double mutant containing both deletions. The secondary structure of the resulting 96-nucleotide RNA, studied using structure-specific ribonucleases, was found to resemble the central portion of 5S RNA. PMID- 1614849 TI - How are tRNAs and mRNA arranged in the ribosome? An attempt to correlate the stereochemistry of the tRNA-mRNA interaction with constraints imposed by the ribosomal topography. AB - Two tRNA molecules at the ribosomal A- and P-sites, with a relatively small angle between the planes of the L-shaped molecules, can be arranged in two mutually exclusive orientations. In one (the 'R'-configuration), the T-loop of the A-site tRNA faces the D-loop of the P-site tRNA, whereas in the other (the 'S' configuration) the D-loop of the A-site tRNA faces the T-loop of the P-site tRNA. A number of stereochemical arguments, based on the crystal structure of 'free' tRNA, favour the R-configuration. In the ribosome, the CCA-ends of the tRNA molecules are 'fixed' at the base of the central protuberance (the peptidyl transferase centre) of the 50S subunit, and the anticodon loops lie in the neck region (the decoding site) of the 30S subunit. The translocation step is essentially a rotational movement of the tRNA from the A- to the P-site, and there is convincing evidence that the A-site must be located nearest to the L7/L12 protuberance of the 50S subunit. The mRNA in the two codon-anticodon duplexes lies on the 'inside' of the 'elbows' of the tRNA molecules (in both the S-type and R-type configurations), and runs up between the two molecules from the A- to the P-site in the 3' to 5'-direction. These considerations have the consequence that in the S-configuration the mRNA in the codon-anticodon duplexes is directed towards the 50S subunit, whereas in the R-configuration it is directed towards the 30S subunit. The results of site-directed cross-linking experiments, in particular cross-links to mRNA at positions within or very close to the codons interacting with A- or P-site tRNA, favour the latter situation. This conclusion is in direct contradiction to other current models for the arrangement of mRNA and tRNA on the ribosome. PMID- 1614851 TI - The weak, fine-tuned binding of ubiquitous transcription factors to the Il-2 enhancer contributes to its T cell-restricted activity. AB - The T lymphocyte-specific enhancers of the murine and human Interleukin 2 (Il-2) genes harbour several binding sites for ubiquitous transcription factors. All these sites for the binding of AP-1, NF-kB or Oct-1 are non-canonical sites, i.e. they differ in one or a few base pairs from consensus sequences for the optimal binding of these factors. Although the factors bind weakly to these sites, the latter are functionally important because their mutation to non-binding sites results in a decrease of inducible activity of the Il-2 enhancer. Conversion of three sites to canonical binding sites of Octamer factors, AP-1 and NF-kB results in a drastic increase in enhancer activity and the induction of the Il-2 enhancer in non-T cells, such as B cell lines, murine L cells and human HeLa cells. The introduction of two or three canonical sites into the enhancer leads to a further increase of its activity. Il-2 enhancer induction is also observed in B cells when the concentration of AP-1 and Oct factors increases as a result of cotransfections with FosB and Octamer expression plasmids. When Il-2 enhancer constructs carrying canonical factor binding sites were injected into Xenopus oocytes the strong binding of ubiquitous factors substantially overcomes the silencing effect of negatively acting factors present in resting primary T lymphocytes. These results suggest a fine-tuned interplay between ubiquitous and lymphoid-specific factors binding to and transactivating the Il-2 enhancer and show that the binding affinity of ubiquitous factors to the enhancer contributes to its cell-type specific activity. Moreover, we believe that a dramatic increase of transcriptional activity brought about by single point mutations at strategic important factor binding sites may also have relevance to the activation of nuclear oncogenes. PMID- 1614852 TI - An African swine fever virus gene with homology to DNA ligases. AB - Sequence analysis of the SalI g region of the genome of a virulent isolate of ASFV (Malawi Lil 20/1) has revealed an open reading frame with the potential to encode a 48 kilodalton (kD) polypeptide which has significant homology with eukaryotic and prokaryotic DNA ligases. This ASFV encoded gene also contains the putative active site region of DNA ligases including the lysine residue which is necessary for enzyme-adenylate adduct formation, but lacks the C-terminal basic region conserved in other eukaryotic DNA ligases. A novel [32P]-labelled potential DNA ligase-adenylate adduct of M(r) 45 kD was observed upon incubation of ASFV infected cell cytoplasmic extracts with alpha-[32P]-ATP and subsequent analysis of products by SDS/PAGE. These data together suggest that ASFV encodes its own DNA ligase. PMID- 1614853 TI - Two nucleotides next to the anticodon of cytoplasmic rat tRNA(Asp) are likely generated by RNA editing. AB - The nucleotide sequences of major cytoplasmic tRNA(Asp) from rat liver and rat ascites hepatoma comprise a U32 and C33 next to the anticodon as was confirmed by different procedures. Additionally we identified a tRNA(Asp) with C32 and U33 in a minor proportion. We have shown earlier that the tRNA(Asp) gene is part of a cluster of tRNA genes which is amplified at least ten times in the rat nuclear genome. Six independent isolated clones display identical sequences in the coding region of the tRNA(Asp) gene which differ from tRNA(Asp) in having C32 and T33. Using a combination of single-strand conformation polymorphism (SSCP) analyses and direct sequencing of polymerase chain reaction (PCR) products we have now demonstrated that no variant allele of the tRNA(Asp) gene with T32 and C33 exists in the rat genome. Together with the RNA sequencing data these findings strongly indicate that major rat tRNA(Asp) is generated by post-transcriptional pyrimidine transitions at positions 32 and 33 and that the minor tRNA(Asp) is its unedited precursor. PMID- 1614854 TI - A single amino acid substitution reduces the superhelicity requirement of a replication initiator protein. AB - The origin of rolling circle replication in filamentous coliphage consists of a core origin that is absolutely required and an adjacent replication enhancer sequence that increases in vivo replication 30 to 100-fold. The core origin binds the initiator protein (gpII) which either nicks or relaxes negatively superhelical replicative form DNA (RFI). Nicking at the origin, but not relaxation, leads to initiation of DNA replication. Our results indicate that the ratio of nicking to relaxation (nicking-closing) in vitro depends on the superhelical density of the substrate. We have studied the effect of a single amino acid substitution in gpII, which allows wild-type levels of replication in the absence of the enhancer, on origin nicking and binding. The enhancer independent mutation yields more nicking and less relaxation of RFI, compared to the wild-type protein. The mutant gpII also shows a reduced requirement for superhelicity of the substrate in the nicking reaction. At the same time, the mutant gpII increases the cooperativity of protein-protein interactions in origin binding. We propose that the relaxation activity of gpII negatively regulates replication initiation, and that both increase in the negative superhelicity of the substrate and action of the replication enhancer may antagonize the relaxation activity. PMID- 1614855 TI - Targeted alterations in yeast artificial chromosomes for inter-species gene transfer. AB - In order to facilitate alterations of large DNA molecules for their introduction into mammalian cells we have characterised the mechanism of site-specific modifications in yeast artificial chromosomes (YACs). Newly developed yeast integration vectors with dominant selectable marker genes allow targeted integration into left (centromeric) and right (non-centromeric) YAC arms as well as alterations to the human derived insert DNA. In transformation experiments, integration proceeds exclusively by homologous recombination although yeast prefers linear ends of homology for predefined insertions. Targeted regions can be rescued which expedite the cloning of internal human sequences and the identification of 5' and 3' YAC/insert borders. Integration of the neomycin resistance gene into various parts of the YAC allowed the transfer and stable integration of large DNA molecules into a variety of mammalian cells including embryonic stem cells. PMID- 1614856 TI - Serum, AP-1 and Ets-1 stimulate the human ets-1 promoter. AB - The ets-1 proto-oncogene codes for a transcription factor. In order to understand how ets-1 is regulated, we have cloned its promoter. We show that the promoter is inducible by serum and expression of c-Fos and c-Jun, and it is positively auto regulated by its gene product. A 50 base-pair sequence is sufficient to confer c Fos + c-Jun and c-Ets-1 responsiveness to a heterologous promoter. This element contains two AP1 and one Ets-1 like motifs. Striking, AP-1 and Ets-1 motifs are found in oncogene responsive units (ORU's) of other promoters, suggesting that combining these motifs is a common mechanism for generating mitogen responsive transcription elements. PMID- 1614857 TI - Structural and functional features of cis-acting sequences in the basic replicon of plasmid ColIb-P9. AB - We have structurally and functionally analyzed the cis-elements essential for ColIb-P9 plasmid DNA replication. The putative oriV region encompassed a region of 172 base pairs (bp) located 152 bp downstream of the repZ gene. A typical dnaA box found in this region proved nonessential for the DNA replication of ColIb-P9. The ssi signal of ColIb-P9 is a homologue of the G-sites of R1 and R100 plasmids. Deletion of the G-site led to 1.5-fold reduction of the copy number, suggesting that although this G-site is not essential, it is important for efficient ColIb P9 DNA replication. In addition, the ColIb-P9 replicon is highly and extensively homologous with the P307 (RepFIC) replicon, and highly homologous with the R100 (RepFIIA) replicon around the G-site region. These facts imply a common ancestry from which the plasmids have evolved. PMID- 1614859 TI - Computer methods for locating kinetoplastid cryptogenes. AB - RNA editing in the mitochondria of kinetoplastid protoza involves the insertion and/or deletion of precise numbers of uridine residues at precise locations in the numbers of uridine residues at precise locations in the transcribed RNA of certain genes. These genes are known as cryptogenes. In this paper we study computational algorithms to search for unknown cryptogenes and for the associated templates for insertion of uridines, gRNA sequences. The pairwise similarity search algorithm of Smith and Waterman (1) is modified to study this problem. The algorithm searches for unknown gRNAs given the cryptogene sequence. The method is tested on 4 known cryptogenes from L.tarentolae which are known to have 7 associated gRNAs. The statistical distribution of the longest gRNA when comparing random sequences is derived. Finally we develop an algorithm to search for cryptogenes using amino acid sequences from related proteins. PMID- 1614858 TI - A DNA polymerase from the archaeon Sulfolobus solfataricus shows sequence similarity to family B DNA polymerases. AB - The gene encoding the thermostable DNA polymerase from the archaeon Sulfolobus solfataricus (strain MT 4) was isolated by means of two degenerate oligonucleotide probes. They were designed on the basis of partial enzyme amino acid sequences. The gene was found to encode a 882 residues polypeptide chain with a deduced molecular mass of about 100 kDa. By comparison with other archaeal genes, putative regulatory sites were identified in the gene-flanking regions. By computer-assisted homology search, several sequence similarities among S. solfataricus and family B DNA polymerases were found. In addition, conserved sequence motifs, implicated in the 3'-5' exonuclease activity of E. coli DNA polymerase I and shared by various family A and B DNA polymerases, were also identified. This result suggests that the proofreading domains of all these enzymes are evolutionarily related. PMID- 1614860 TI - Uranyl photofootprinting of triple helical DNA. AB - Two triple helix structures (15-mers containing only T.A-T triplets or containing mixed T.A-T and C.G-C triplets) have been studied by uranyl mediated DNA photocleavage to probe the accessibility of the phosphates of the DNA backbone. Whereas the phosphates of the pyrimidine strand are at least as accessible as in double stranded DNA, in the phosphates of the purine strand are partly shielded and more so at the 5'-end of the strand. With the homo A/T target increased cleavage is observed towards the 3'-end on the pyrimidine strand. These results show that the third strand is asymmetrically positioned along the groove with the tightest triple strand double strand interactions at the 5'-end of the third strand. The results also indicate that homo-A versus mixed A/G 'Hoogsteen-triple helices' have different structures. PMID- 1614861 TI - Corruption of genomic databases with anomalous sequence. AB - We describe evidence that DNA sequences from vectors used for cloning and sequencing have been incorporated accidentally into eukaryotic entries in the GenBank database. These incorporations were not restricted to one type of vector or to a single mechanism. Many minor instances may have been the result of simple editing errors, but some entries contained large blocks of vector sequence that had been incorporated by contamination or other accidents during cloning. Some cases involved unusual rearrangements and areas of vector distant from the normal insertion sites. Matches to vector were found in 0.23% of 20,000 sequences analyzed in GenBank Release 63. Although the possibility of anomalous sequence incorporation has been recognized since the inception of GenBank and should be easy to avoid, recent evidence suggests that this problem is increasing more quickly than the database itself. The presence of anomalous sequence may have serious consequences for the interpretation and use of database entries, and will have an impact on issues of database management. The incorporated vector fragments described here may also be useful for a crude estimate of the fidelity of sequence information in the database. In alignments with well-defined ends, the matching sequences showed 96.8% identity to vector; when poorer matches with arbitrary limits were included, the aggregate identity to vector sequence was 94.8%. PMID- 1614862 TI - Two distinct pathways of interferon induction as revealed by 2-aminopurine. AB - Activation and repression of IFN gene expression are controlled primarily at the transcriptional level. In order to elucidate some aspects of the induction mechanism of the IFN genes, we examined the effects of different treatments on IFN production in L929 cells, a well-characterized system, and in primary spleen cells. Our results indicate that 2-Aminopurine (2-AP) inhibits type I IFN (IFN alpha and IFN-beta) induction in L929 cells but not in spleen cells. In L929 cells, 2-AP inhibited the induction of the MuIFN-beta promoter and of promoters containing tetrahexamer and PRDII sequences linked to a reporter gene. Inhibition of activation of the inducible factors binding to the MuIFN-beta promoter and sub elements was also observed. In contrast, factors binding to the MuIFN-beta promoter are present constitutively in spleen cell nuclei and their activity is not inhibited by 2-AP. These results suggest that 2-AP inhibits IFN-beta gene induction in L929 cells through blocking of activation of the inducible DNA binding factors which interact with the IFN-beta promoter. PMID- 1614863 TI - Synergistic induction of promoters containing metal- and glucocorticoid responsive elements. AB - We have shown that it is possible to synergistically activate gene transcription when several glucocorticoid responsive elements (GREs) and metal responsive elements (MREs) that coexist within the same promoter are induced simultaneously. To demonstrate this, additional GREs were introduced into a human metallothionein IIA (hMT-IIA) promoter in which some constitutive elements had been deleted. The transcriptional strength and inducibility of the modified hMT-IIA promoters were studied in transient expression experiments using the CAT gene as a reporter. As a result of synergistic activation of transcription by CdCl2 and dexamethasone, the induced expression levels of the modified promoters were significantly higher than those obtained with wild-type hMT-IIA. Since the increase in inducible expression was not accompanied by a concominant increase in basal levels, the inducibility of the modified MT promoters was up to 6-fold higher. The degree of transcriptional synergism was shown to depend on the position and the number of GREs introduced. Thus, the engineering of synthetic promoters that include both GREs and MREs should offer the opportunity to develop a new series of improved inducible mammalian expression vectors. PMID- 1614864 TI - Heterologous activation of the actinorhodin biosynthetic pathway in Streptomyces lividans. AB - A DNA fragment of Streptomyces fradiae is able to activate the antibiotic actinorhodin biosynthetic pathway when cloned in Streptomyces lividans. The activator DNA region has been sequenced and its transcription initiation and termination sites accurately mapped in vivo. This DNA encodes a 132 nucleotides long transcript which is apparently responsible for the actinorhodin production phenotype, possibly acting as an antisense RNA. The sequence of the activator gene revealed no homology with any other known Streptomyces coelicolor genes concerned with actinorhodin biosynthesis or its pleiotropic regulation. PMID- 1614865 TI - The influence of single base triplet changes on the stability of a pur.pur.pyr triple helix determined by affinity cleaving. AB - The influence of sixteen base triplet changes at a single position within a pur.pur.pyr triple helix was examined by affinity cleaving. For the 15 base pair target site studied here, G.GC, A.AT and T.AT triplets stabilize a triple helix to a greater extent than the other 13 natural triplets (pH = 7.4, 25 degrees C). Weaker interactions were detected for the C.AT, A.GC and T.CG triplets. The absence of specific, highly stabilizing interactions between third strand bases and the CG or TA base pairs demonstrates a current sequence limitation to formation of this structure. Models for the two dimensional base triplet interactions for all possible 16 natural triplets are presented. PMID- 1614866 TI - Stable fluorescent complexes of double-stranded DNA with bis-intercalating asymmetric cyanine dyes: properties and applications. AB - The synthesis, proof of structure, and the absorption and fluorescence properties of two new unsymmetrical cyanine dyes, thiazole orange dimer (TOTO; 1,1'-(4,4,7,7 tetramethyl-4,7- diazaundecamethylene)-bis-4-[3-methyl-2,3-dihydro-(benzo-1,3 thiaz ole)-2- methylidene]-quinolinium tetraiodide) and oxazole yellow dimer (YOYO; an analogue of TOTO with a benzo-1,3-oxazole in place of the benzo-1,3 thiazole) are reported. TOTO and YOYO are virtually non-fluorescent in solution, but form highly fluorescent complexes with double-stranded DNA (dsDNA), up to a maximum dye to DNA bp ratio of 1:4, with greater than 1000-fold fluorescence enhancement. The dsDNA-TOTO (lambda max 513 nm; lambda maxF 532 nm) and dsDNA YOYO (lambda max 489 nm; lambda maxF 509 nm) complexes are completely stable to electrophoresis on agarose and acrylamide gels. Mixtures of restriction fragments pre-labeled with ethidium dimer (EthD; lambda maxF 616 nm) and those pre-labeled with either TOTO or YOYO were separated by electrophoresis. Laser excitation at 488 nm and simultaneous confocal fluorescence detection at 620-750 nm (dsDNA-EthD emission) and 500-565 nm (dsDNA-TOTO or dsDNA-YOYO emission) allowed sensitive detection, quantitation, and accurate sizing of restriction fragments ranging from 600 to 24,000 bp. The limit of detection of dsDNA-TOTO and YOYO complexes with a laser-excited confocal fluorescence gel scanner for a band 5-mm wide on a 1-mm thick agarose gel was 4 picograms, about 500-fold lower than attainable by conventional staining with ethidium bromide. PMID- 1614867 TI - Promoter specificity of the two transcriptional activation functions of the human oestrogen receptor in yeast. AB - We have previously demonstrated that the human oestrogen receptor (hER) contains two transcriptional activation functions located in the N-terminal region (TAF-1) and in the hormone binding domain (TAF-2), which can act both independently and synergistically in a promoter- and cell-specific manner in animal cells. We have also demonstrated that hER can activate transcription from chimaeric oestrogen responsive GAL1 promoters in yeast, and shown that transcriptional activation was due to TAF-1, whereas TAF-2 showed little, if any, transcriptional activity on these promoters. By using a more complex promoter derived from the URA3 gene, we now show that TAF-2 is also active in yeast, and that the activities of TAF-1 and TAF-2 are promoter-context-specific in yeast. We also confirm that the agonistic activity of 4-hydroxytamoxifen (OHT) can be ascribed to the activity of TAF-1. PMID- 1614868 TI - Tissue- and cell-specific expression of human sn-glycerol-3-phosphate dehydrogenase in transgenic mice. AB - Comparison of the promoter sequence for the sn-glycerol-3-phosphate dehydrogenase (GPDH, EC 1.1.1.8) genes in mice and humans showed that there were three promoter domains conserved in evolution (1). To study the functional organization of the GPDH promoter, we generated transgenic mice carrying the complete human gene, GPD1. The level of human and mouse GPDH activity was measured in each tissue and the amount of human-mouse GPDH heterodimer was used as a sensitive indicator of cell-specific expression of GPD1. During postnatal development and in adult tissues of the transgenic mice, human GPDH was expressed at levels that corresponded closely to the expression of the endogenous mouse gene, Gdc-1. Surprisingly, deletion of the evolutionarily conserved fat-specific elements (FSE) in the proximal promoter region failed to reveal any alterations in GPD1 expression that were specific for either white or brown adipose tissue. PMID- 1614869 TI - Zfp-37, a new murine zinc finger encoding gene, is expressed in a developmentally regulated pattern in the male germ line. AB - To begin to examine the function in the mouse testis of genes containing the zinc finger motif, we have screened an adult mouse total testis cDNA library with probes to a conserved region of zinc fingers. We have isolated cDNAs for a new murine zinc finger encoding gene that has been designated Zfp-37. Northern blot hybridization analysis revealed Zfp-37 transcripts at high levels in the testis, the only adult tissue in which Zfp-37 expression was observed. Zfp-37 was also expressed at lower levels in the mid-gestation embryo and placenta. The major testicular transcripts are 2.3 and 2.6 kb. A 4.0 kb transcript was detected at lower levels in the testis as well as in embryo and placenta. Northern blot and in situ hybridization analysis revealed that expression of Zfp-37 was most abundant in germ cells which have completed meiosis and are undergoing the complex morphogenetic changes of spermiogenesis. The pattern of expression of Zfp 37 and the presence of the zinc finger domain suggest that Zfp-37 may have a role in regulating spermiogenesis. PMID- 1614870 TI - Identification of an enhancer involved in the melanoma-specific expression of the tumor antigen melanotransferrin gene. AB - Melanotransferrin (MTf) is a tumor associated antigen found in abundance on the surface of melanoma cells. It is a transferrin-like protein found in low amount in most adult tissues and whose gene is reminiscent of house-keeping genes. With the goal of understanding the regulatory mechanisms which might explain the enhancement of expression in tumor cells, we report here the characterization of a regulatory element located 2 kbp upstream from the promoter and whose deletion specifically impairs gene expression in melanoma cells; we show that this element is part of an enhancer composed of two modules which are each the target for the AP1 transcription factor. The two modules present a synergistic mode of action specific for melanoma cells which requires both of the 130 bp away AP1 sites. Furthermore, we show that the enhancer behaves differently according to the promoter context. PMID- 1614871 TI - RNP-1, an RNA-binding motif is conserved in the DNA-binding cold shock domain. AB - Sequence analysis has shown that there is a short motif of 8 amino acids, corresponding to the RNP-1 motif found in canonical RNA-binding domains, which is common to two families of apparently unrelated proteins. Many RNA-binding proteins contain the RNP-1 and RNP-2 motifs in an RNA-binding domain. The cold shock domain (CSD) family of proteins, which includes several transcription factors which have been shown to bind to DNA, has now been identified to contain a motif similar to RNP-1. A non-redundant protein sequence database was searched with regular expressions and with a weight/residue position matrix of the RNP-1 motif resulting in the identification of numerous known members of the RNA binding family of proteins. In addition, the search identified that the CSD containing family of proteins includes a motif which is almost identical to the RNP-1 motif. A determination of the statistical significance of this analysis showed that the RNP-1 motifs from these two families of proteins are indeed similar. PMID- 1614872 TI - Characterization of the human rod transducin alpha-subunit gene. AB - The human rod transducin alpha subunit (Tr alpha) gene has been cloned. A cDNA clone, HG14, contained a 1.1 kb insertion when compared with the human Tr alpha cDNA published by Van Dop et al. (1). Based on two overlapping clones isolated from a human genomic library, the human Tr alpha gene is 4.9 kb in length and consists of nine exons interrupted by eight introns. Northern blots of human retina total RNA showed that the gene is transcribed by rod photoreceptors into two species of mRNA, 1.3 kb and 2.4 kb in size. Apparently, this is the result of alternative splicing. Two putative transcription initiation sites were determined by primer extension and S1 nuclease protection assays. The putative promoter regions of the human and mouse Tr alpha genes have an identity of 78.1%. As found in the mouse gene (2), no TATA consensus sequence is present in the human gene. PMID- 1614873 TI - WORDUP: an efficient algorithm for discovering statistically significant patterns in DNA sequences. AB - We present here a fast and sensitive method designed to isolate short nucleotide sequences which have non-random statistical properties and may thus be biologically active. It is based on a first order Markov analysis and allows us to detect statistically significant sequence motifs from six to ten nucleotides long which are significantly shared (or avoided) in the sequences under investigation. This method has been tested on a set of 521 sequences extracted from the Eukaryotic Promoter Database (2). Our results demonstrate the accuracy and the efficiency of the method in that the sequence motifs which are known to act as eukaryotic promoters, such as the TATA-box and the CAAT-box, were clearly identified. In addition we have found other statistically significant motifs, the biological roles of which are yet to be clarified. PMID- 1614876 TI - ApoI, a unique restriction endonuclease from Arthrobacter protophormiae which recognizes 5' RAATTY 3'. PMID- 1614874 TI - Distinct activation of murine interferon-alpha promoter region by IRF-1/ISFG-2 and virus infection. AB - Virus infection in mouse L929 cells activates expression of interferon-alpha 4 (IFN-alpha 4), but not IFN-alpha 6. The integrity of a symmetrical sequence, GTAAAGAAAGT (alpha F1 site); (-103 to -93), present in the 35 nucleotide (nt) long inducible element (IE) (-109 to -75) of the alpha 4 promoter region is essential for the virus-induced expression. In the present study, we have shown that the interferon regulatory factor 1 (IRF-1) can induce expression of both IFN alpha 4 and -alpha 6 in a transient expression assay. Virus infection cooperates with IRF-1 and further enhances transcription from the alpha 4 promoter, but inhibits the IRF-1-mediated expression from the alpha 6 promoter. The virus mediated induction is determined by both IRF-1 and alpha F1 sites, while activation by IRF-1 in a cotransfection assay is not greatly influenced by the alpha F1 sequence. The activation of IFN-alpha gene promoters by IRF-1 was limited to the transient expression assay. The integrated alpha 4 promoter or the endogenous IFN-alpha genes could not be induced by transfection with IRF-1 expressing plasmid and IRF-1 did not up-regulate expression of the endogenous IRF 1 gene. However, expression of IRF-1 alone was sufficient to up-regulate the expression of two IFN stimulated genes, 2',5' oligoadenylate synthetase (OAS) and interferon stimulated (ISG)-15 gene. These results suggest that induction of IFN alpha gene expression by virus infection requires cooperation between IRF-1 and another factor(s) that binds to the alpha F1 sequence. PMID- 1614875 TI - A conserved family of genes related to the testis determining gene, SRY. PMID- 1614877 TI - MfoAI, a novel isoschizomer of HaeIII from Mycobacterium fortuitum recognizing 5' GG/CC-3'. PMID- 1614878 TI - MhaAI, a novel isoschizomer of PstI from Mycobacterium habana recognizing 5' CTGCA/G-3'. PMID- 1614879 TI - Bovine sequences in rodent DNA. PMID- 1614880 TI - Nucleotide sequence of a cDNA encoding another Trypanosoma cruzi acidic ribosomal P2 type protein (TcP2b). PMID- 1614881 TI - Nucleotide sequence of a cDNA encoding a Trypanosoma cruzi acidic ribosomal PO protein: a novel C-terminal domain in T. cruzi ribosomal P proteins. PMID- 1614882 TI - B region variant of the estrogen receptor gene. PMID- 1614883 TI - Characterisation of BciBII, an isoschizomer of BstNI from a strain of Bacillus circulans B. PMID- 1614884 TI - BavAI, a restriction endonuclease from Bacillus alvei. PMID- 1614885 TI - Isolation and characterisation of restriction endonuclease BcuAI from Bacillus cereus A. PMID- 1614886 TI - Chemical cross linking subtraction (CCLS): a new method for the generation of subtractive hybridisation probes. PMID- 1614887 TI - A random-PCR method (rPCR) to construct whole cDNA library from low amounts of RNA. PMID- 1614888 TI - Electroporation in 'intracellular' buffer increases cell survival. PMID- 1614889 TI - A novel PCR method for amplifying exons (or genes) over intragenic (or intergenic) regions in the genome. PMID- 1614892 TI - Making a difference in health policy. PMID- 1614891 TI - Where and when does change begin? PMID- 1614893 TI - Health promotion and disease prevention: toward excellence in nursing practice and education. PMID- 1614894 TI - A nursing view of the United States-Iraq war: psychosocial health consequences. PMID- 1614896 TI - Nursing education in modern Turkey. PMID- 1614895 TI - Developing community leadership in healthy cities: the Indiana model. PMID- 1614890 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1614897 TI - 'Will universal precautions protect me?' A look at staff nurses' attitudes. PMID- 1614898 TI - Empowering nurses for professional practice. PMID- 1614899 TI - High-flow sheaths for pediatric fluid resuscitation: a comparison of flow rates with standard pediatric catheters. AB - We evaluated high-flow intravenous devices designed specifically for fluid resuscitation of infants and children. Fluid flow rates with 4-, 5-, and 6-Fr high-flow sheaths and 18-, 20-, and 22-gauge catheters were measured and compared. Flow rate is significantly faster with the 4-Fr sheath (P less than 0.0001) than with the 18-, 20-, or 22-gauge catheter. The high flow rates possible with the sheaths make them ideal for use in patients who require rapid fluid resuscitation. PMID- 1614900 TI - Diagnosing abdominal pain in a pediatric emergency department. AB - We undertook a prospective study of 377 children (two to 16 years old) presenting with abdominal pain to determine: 1) common discharge diagnoses; 2) what signs and symptoms are associated with appendicitis; and 3) follow-up of patients discharged from the emergency department (ED). Nine diagnoses accounted for 86% of all diagnoses made. The most common final diagnosis was "abdominal pain" (36%). The following findings were significantly associated with appendicitis: vomiting, right lower quadrant(RLQ) pain, tenderness, and guarding (all P less than 0.001). Ninety-seven percent (28/29) of patients with appendicitis had at least two of these four signs and symptoms, as did 28% (96/348) of patients without appendicitis. The sensitivity of the model is 0.96, and the specificity is 0.72 (positive predictive value = 0.24; negative predictive value = 0.99). Of the patients contacted within one week of the visit (237), 75% reported that the pain had resolved (mean contact time, 2.6 days). We conclude that 1) patients presenting to the ED with abdominal pain often leave with the diagnosis of abdominal pain; 2) of the patients contacted, the majority reported that their pain has resolved; and 3) a diagnosis of appendicitis should be considered in any patient with any two of the following signs or symptoms: vomiting, guarding, tenderness, or RLQ pain. Such patients should be evaluated and observed carefully for the possible diagnosis of appendicitis. PMID- 1614901 TI - A one-year series of pediatric ED water-related injuries: the Hawaii EMS-C project. AB - During a 12-month period ending on November 30, 1988, data on 133 pediatric patients visiting a pediatric emergency department with water-related injuries were collected. Of these patients, 70% were male. There were 13 submersions, seven cases of head trauma, three cases of neck trauma, 88 cases of external injury, and 34 other injuries. Incidents took place at beaches (75%) in public pools (12%), in friends' pools (4%), and in home pools (4%). Eighty-six percent of the cohort knew how to swim. Swimming, playing, and surfing activity accounted for most of the injuries. Measures for prevention are described. PMID- 1614902 TI - Metal detectors: an alternative approach to the evaluation of coin ingestions in children? AB - Foreign body ingestions constitute a common problem in pediatric emergency medicine. Recent data indicate that, despite current recommendations, most children who ingest coins do not undergo radiologic evaluation. The purpose of this study was to determine the accuracy of a metal detector in locating coins in a model simulating coin ingestions in children. Initially, the distance between the anterior chest wall (ACW) and the esophagus was measured on 17 chest computed tomograms obtained on children between the ages of three months and six years. Subsequently, a distance equal to the mean ACW-to-gastroesophageal junction measurement was marked across the investigator's forearm. A second investigator then attempted to detect the presence of the coin through the forearm by using a Super Scanner (Garrett Security Systems, Inc, Garland, TX) metal detector. The study was conducted in a blinded manner and consisted of 50 attempts equally divided among pennies, nickels, dimes, quarters, and controls (no coin). The accuracy of the metal detector in identifying the presence or absence of coins in our model was 100%. We conclude that the metal detector evaluated by us is highly accurate in identifying coins through human tissues and that it should become a valuable and practical tool in the evaluation of children following a coin ingestion. PMID- 1614903 TI - Pulmonary aspiration of activated charcoal: a complication of its misuse in overdose management. PMID- 1614904 TI - An unsuspected alkaline battery foreign body presenting as malignant otitis externa. AB - We describe a case of an unsuspected button battery foreign body in the ear canal causing symptoms that mimic malignant otitis externa in a previously healthy 13 year old. Button batteries in the ear canal may cause extensive liquefactive necrosis of the surrounding tissue by leaking an alkaline electrolyte solution. Suspicion of a foreign body should be maintained in any child presenting with a complicated otitis externa. Prompt evaluation and removal of button batteries are necessary to prevent tissue destruction. PMID- 1614905 TI - Vitamin K deficiency, intracranial hemorrhage, and a subgaleal hematoma: a fatal combination. AB - An exclusively breast-fed infant, who did not receive vitamin K prophylaxis at birth, presented with signs of raised intracranial pressure. Her clinical course was compounded by a lumbar puncture, which revealed blood in the cerebrospinal fluid, and a large subgaleal hematoma, which developed at the puncture site of an attempted scalp vein catheterization, resulting in coning, hypovolemic shock, and death. A major coagulopathy was present, probably caused by vitamin K deficiency. The necessity for vitamin K prophylaxis in all newborns and the timing of lumbar puncture in the critically ill child are discussed. PMID- 1614906 TI - Postprandial hypoglycemia in an infant associated with propranolol. PMID- 1614907 TI - Measurement of severity for nonhospitalized injuries in the pediatric age group. AB - To better classify minor injuries in the pediatric outpatient population, we empirically developed a scale to predict functional impairment, one week and one month postinjury, based on data available at the time of care. A sample of 857 injured children aged five to 19 years was randomly split into two subsamples. Using logistic regression techniques, predictive models were developed and confirmed on the subsamples and then applied to the full sample. Age, location of injury, and type of injury were predictive of impairment one week post-injury; however, type of injury was the only consistently significant predictor. Type of injury, specifically fracture, dislocation, and sprain, and location of injury (lower extremity) were significant predictors of functional impairment one month postinjury; however, once again, the type of injury was the only variable consistently significant across all models. Other than the type of injury, the variables available at the time of care were too uniform between disabled and nondisabled patients to be useful in developing a severity scale for minor injuries. We conclude that other outcome measurements or scale development techniques should be explored to develop a useful classification scheme for minor injuries. PMID- 1614908 TI - Interfacing with police in the pediatric emergency department. AB - In summary, ED staff and local police departments should make a concerted effort to work together. The ED director should develop management protocols in conjunction with local police chiefs to plan strategies in advance. It is helpful to provide "orientation sessions," so that each group of professionals knows what to expect of the other. It may also be helpful to arrange tours of the ED so that police know where to go when they are called to the ED. All of these efforts should foster better care of children in the ED and will reduce tensions between the dedicated groups who work with such children. PMID- 1614909 TI - Acute pancreatitis in children. AB - Acute pancreatitis in childhood is not a rare condition, and it should be considered in all children presenting with acute abdominal complaints. A complete history should be obtained, with emphasis on recent trauma or infection, current medications, and the presence of any chronic diseases. After a thorough physical examination, simple ancillary studies including noninvasive imaging techniques will confirm the clinical suspicion. Appropriate aggressive treatment, instituted early, will help to reduce the associated morbidity and mortality. Most children with acute pancreatitis will recover with conservative management and suffer no significant long-term sequelae. PMID- 1614910 TI - Interpretive electrocardiographs. PMID- 1614911 TI - Management of asthma. PMID- 1614912 TI - A fatal case of colic. AB - The potential causes of excessive, prolonged crying in early infancy represent a broad range of conditions. The underlying etiology causing an acute episode of crying may not be recognized in a single emergency department encounter. An adverse outcome may result when an infant with unexplained crying is discharged with a diagnosis of colic. PMID- 1614913 TI - Asymptomatic subclavian steal syndrome in children following cardiac surgery: a potential hazard with re-operation? AB - We describe a case of fatal hypoxic-ischemic encephalopathy, leading to brain death following the modified Fontan procedure in a child with asymptomatic subclavian steal syndrome (SSS). This patient's brain death was most likely multifactorial in view of his postoperative course. However, we believe that the presence of the SSS contributed to the abnormal cerebral circulation during surgery and postoperatively, leading to brain death. The presence of SSS in patients undergoing an open-heart procedure may be a risk factor for cerebral ischemia or brain death. PMID- 1614915 TI - Pulsed wave and color Doppler findings in congenital pulmonary vein stenosis. AB - A premature infant presented at 8 weeks of age with respiratory failure and pulmonary hypertension. Two-dimensional echocardiography was not diagnostic but color flow imaging and pulsed Doppler examination revealed turbulent and continuous pulmonary venous flow. Differing patterns of disturbed flow suggested varying severity of obstruction in individual pulmonary veins. The Doppler findings are compared to the angiographic and autopsy data. PMID- 1614914 TI - Hypertrophic cardiomyopathy in mucopolysaccharidoses: regression after bone marrow transplantation. AB - Mucopolysaccharide storage disease (MPS) presents clinically with a broad spectrum of abnormalities, among which cardiovascular involvement has been described. The echocardiographic findings have recently been reported for the various types of MPS. Among these, asymmetric septal hypertrophy (ASH) has been documented. We present a case of a 9-year-old girl suffering from type I MPS, atypical variant, with echocardiographic signs of ASH. She was given a bone marrow transplant after which the hypertrophic cardiomyopathy regressed. PMID- 1614916 TI - Supraventricular tachyarrhythmias, congenital heart disease, and sudden cardiac death. AB - The etiologies of sudden cardiac death following the surgical treatment of congenital heart defects remain uncertain. A young patient with prior repair of partial anomalous pulmonary venous return is presented, in whom brief episodes of a supraventricular tachyarrhythmia (rate 170/min) were documented to result in ventricular fibrillation. This unusual sequence may represent a basis for unexplained sudden cardiac death in other patients following atrial surgical procedures for the treatment of congenital heart disease. PMID- 1614918 TI - Absence of an aortic valve cusp, a cause of severe aortic regurgitation in infancy. AB - Congenital aortic regurgitation is an extremely rare cardiac lesion. This is a case report of an infant with a severe degree of valve regurgitation due to absence of the noncoronary aortic cusp. We show the echocardiographic, angiographic, and surgical aspects of the case, emphasizing the importance of a precise anatomical diagnosis and the problems of early valve replacement. PMID- 1614917 TI - Scimitar syndrome with absence of the right pulmonary artery: a case with volume induced, reversible, left-sided pulmonary hypertension. AB - An infant with scimitar syndrome, absent right pulmonary artery, and systemic blood supply to the right lung presented in severe cardiac failure. Cardiac catheterization revealed suprasystemic pressure of the left pulmonary artery and a high pulmonary vascular resistance. Right-sided pneumonectomy abolished cardiac failure and normalized both pulmonary artery pressure and resistance. Pure volume load affecting one lung--as in this case through absence of the right pulmonary artery plus additional left-to-right shunt from a systemic collateral--can lead to pulmonary hypertension. Early operative intervention can reverse this process and prevent pulmonary vascular disease. PMID- 1614919 TI - Cor triatriatum associated with total anomalous pulmonary venous drainage in the setting of mitral atresia and a restrictive interatrial communication. AB - A rare variant of cor triatriatum is described in which the proximal "accessory" chamber received all four pulmonary veins and drained into the levoatriocardinal vein and then into the innominate vein. The distal "true" chamber contained the left atrial appendage. The left atrioventricular valve was atretic and the interatrial septum was restrictive. PMID- 1614920 TI - Gaucher's disease with mitral valve calcification. PMID- 1614921 TI - Cardiomyopathy in infancy: observations in an epidemiologic study. AB - Cardiomyopathy (Cm), a rare form of cardiac disease in infancy, is receiving increasing attention stimulated by the availability of endocardial biopsy and new forms of therapy. Population-based information on frequency of occurrence, types, and maternal and infant characteristics of this diverse group of heart muscle disorders has been obtained in the course of an etiologic study on cardiovascular disease in infancy. The Baltimore-Washington Infant Study (BWIS) enrolled 2659 infants with heart disease and 2801 control infants between January 1, 1981 and March 31, 1987, a 6-year prevalence of 4.46/1000 live births. Fifty-six infants had cardiomyopathy, in the absence of a structural defect (prevalence 1/10,000). The cases were classified clinicopathologically as follows: dilated Cm (n = 17), hypertrophic Cm (n = 26), tumor (n = 5), endocardial fibroelastosis (n = 5), glycogen storage (n = 1), mucocutaneous lymph node syndrome (n = 1), and infarction (n = 1). Eleven syndromic associations and six metabolic disturbances indicate genetic risk factors. Some of the same syndromes occurred in other infants who had structural cardiac abnormalities. This overlap suggests that embryonic myocardial disease might sometimes be responsible for altered cardiac structures, possibly secondary to hemodynamic changes. Familial myocardial disease occurred in two infants with hypertrophic Cm. The Cm group did not differ by race and sex from controls, but the mothers were of lower educational and occupational status with less private care and with later registration for pregnancy care. The descriptive epidemiology of this population-based case group provides evidence of greater etiologic heterogeneity than has been shown in clinical reports. PMID- 1614922 TI - Grading the severity of congestive heart failure in infants. AB - To determine which variables most accurately define congestive heart failure (CHF) in infants, 41 patients (median age 2.5 months) were graded by four pediatric cardiologists for the presence and severity of CHF based on the following variables: amount of formula consumed per feeding, feeding time, history of diaphoresis or tachypnea, growth parameters, respiratory and heart rates, respiratory pattern, perfusion, presence of edema, diastolic filling sounds, and hepatomegaly. There were 19 patients graded as having no CHF, nine as mild, seven moderate, and six severe CHF. The most sensitive and specific variables (p less than 0.0001) for the presence of CHF were a history of less than 3.5 oz/feed, respiratory rate greater than 50/min, an abnormal respiratory pattern, diastolic filling sounds, and hepatomegaly. Moderate to severe CHF was present when patients took less than 3 oz/feed or greater than 40 min/feed, had an abnormal respiratory pattern with a resting respiratory rate greater than 60/min, and had a diastolic filling sound and moderate hepatomegaly. Severe CHF was accompanied by a heart rate greater than 170/min, decreased perfusion, and severe hepatomegaly. Thus, the grading of the severity of CHF in infants should include an accurate description of these historical and clinical variables. PMID- 1614924 TI - Cor triatriatum sinistrum: one institution's 28-year experience. AB - Twelve patients with cor triatriatum sinistrum were treated over a 28-year period. Their ages ranged from 1 month to 7.5 years. Congestive heart failure was the most common presentation. Cardiac catheterization was performed on six of the 12 patients and a correct diagnosis of cor triatriatum was made on angiography in only four of the six. Of the remaining six patients, three were diagnosed as having cor triatriatum by echocardiography and three by autopsy. Echocardiography is now considered to be the diagnostic modality of choice in our institution. Seven patients were operated on and five died prior to diagnosis or treatment Associated cardiac anomalies included persistent left superior vena cava, atrial septal defects, coarctation of the aorta, and total anomalous pulmonary venous drainage. A right atrial, transseptal approach to the common pulmonary chamber and excision of the left atrial membrane was found to be the treatment of choice and was used in six of the seven patients operated on. One patient died in the postoperative period. Thus, cor triatriatum sinistrum, a rare and potentially lethal congenital cardiac anomaly, can be diagnosed by echocardiography and successfully treated surgically with a low operative mortality. PMID- 1614923 TI - A survey of pediatric management of dyslipidemias in New England. AB - We recently surveyed physicians attending the New England Pediatric Preventive Cardiology Society. Sixteen physicians who actively evaluated children with dyslipidemia completed questionnaires; at least one representative from six of the seven medical schools in New England was included. The survey elicited responses to five hypothetical cases of childhood dyslipidemia which were representative of the types of lipid problems commonly referred to pediatric lipid specialists. Diet modification was the initial treatment of choice of all participants. For any set of lipid values, postpubertal age increased the proportion of respondents who would have prescribed medication. When pharmacologic intervention was elected, resin binders (cholestyramine or cholestipol) and niacin were most commonly prescribed. The responses of the physicians showed considerable variation in the threshold for beginning medications. In summary, this survey suggests substantial variation in the approach to pharmacologic management of pediatric dyslipidemias in the New England region. PMID- 1614925 TI - Juvenile autoimmune thyroiditis and mitral valve prolapse. AB - An increased incidence of mitral valve prolapse (MVP) has been reported in adult patients with autoimmune thyroid disease. The aim of this study was to assess the incidence of MVP in children and adolescents with juvenile autoimmune thyroiditis (JAT). Cardiac echo studies using M-mode, 2D, and Doppler examinations were performed on 23 patients (21 females, 2 males). The patients were studied at a median age of 12 years (range 5-20 years). Only one patient was found to have evidence suggestive of MVP, an incidence (4.3%) similar to that seen in the normal pediatric population. We, therefore, conclude that the incidence of MVP in children and adolescence with JAT is not increased. PMID- 1614926 TI - Anomalous left coronary artery from the main pulmonary trunk: physiologic and clinical importance of its association with persistent ductus arteriosus. AB - Anomalous left coronary artery (ALCA) from the pulmonary trunk presents in early infancy with a clinical picture of failure to thrive, congestive heart failure (CHF), angina-like episodes, and mitral insufficiency. These manifestations which are due to myocardial ischemia may change in the presence of an associated lesion. We present a case and review two previous reports of a patent ductus arteriosus (PDA) associated with this anomaly. Although signs and symptoms are not as clear due to the less impaired coronary perfusion and the presence of a PDA, the presence of mitral insufficiency should raise the possibility of an anomalous coronary artery and, therefore, a cardiac catheterization and angiocardiography are recommended in anticipation of reparative surgery. PMID- 1614927 TI - Care with an indwelling urinary catheter. Tips for avoiding problems in independent and institutionalized patients. AB - Ideally, no patient would have an indwelling urethral catheter. However, certain circumstances require long-term catheterization. In these patients, bacterial colonization is to be expected. Morbidity and mortality related to long-term catheterization can be minimized by attention to the details of catheter care, prompt treatment of often minimally symptomatic catheter-related infections, and attentiveness to changes in patient condition or alternative treatments that may permit catheter removal. PMID- 1614929 TI - Medical implications of obesity. Losing pounds, gaining years. AB - Through thousands of years of starvation and poor nutrition, the human body has become adept at storing scarce nutrients. Today, in the United States and Canada particularly, the combination of sedentary habits and excessive intake of calories is imposing a dual burden on a physiologic system that is ill-equipped to handle it. Unable to rid itself of calories, the body's only defense is to store them all. The end result is obesity, with all its deleterious effects on health and longevity. PMID- 1614928 TI - Animal bites. Guidelines to current management. AB - Several factors need to be considered when evaluating animal bites. These include type of animal involved, specific nature of the wound, circumstances of the attack, interval between injury and treatment, and location of the bite. Of concern are direct destruction of tissue and risk of infection. Use of antibiotic prophylaxis is controversial, but most authorities agree that it is needed for hand wounds, puncture wounds, or "dirty" wounds of any type in any location. The choice of antibiotic is also controversial, but initial empirical treatment generally relies on broad-spectrum coverage. Rabies prophylaxis is indicated for bites by carnivorous wild animals, bats, and unvaccinated domestic animals. Review of the patient's tetanus status is mandatory. PMID- 1614930 TI - Aspiration pneumonia. A threat when deglutition is compromised. AB - Aspiration results from abnormal structure or from dysfunction during the oral, pharyngeal, or esophageal stage of deglutition. Chemically induced inflammation of the lungs and obstruction of the airways may ensue. Feeding and swallowing problems may occur at any age, but they are particularly prevalent in the elderly, and the morbidity and mortality that result from impaired oral intake are now recognized as a major geriatric problem. Aspiration pneumonitis and/or pneumonia has a high morbidity and mortality rate. Medical management is mainly aimed at supportive care with the hope of resolution over time. Complications demand aggressive measures. Prevention of aspiration is apt to be more rewarding than treatment of consequences. All predisposing factors should be carefully assessed by the physician and modified whenever possible. PMID- 1614931 TI - Follow the rules. But tell us if the feds target you unfairly! PMID- 1614932 TI - Exercise for patients with diabetes. Benefits, risks, precautions. AB - Exercise is beneficial in both prevention and control of non-insulin-dependent (type II) diabetes. Whether a patient has insulin-dependent or type II diabetes, a regular exercise program can produce positive changes in the lipid profile, reduce blood pressure and weight, and improve other cardiovascular risk factors. The risks of an exercise program include precipitation of cardiovascular events, damage to the soft tissue and joints of the feet, visual loss, early and delayed hypoglycemia, and hyperglycemia and ketosis. Consequently, a comprehensive clinical assessment to identify potentially harmful diabetic complications and to determine the patient's fitness level is needed before a suitable exercise program can be prescribed. With careful manipulation of insulin doses and home monitoring of blood glucose levels, exercise need not adversely affect glycemic control. Moreover, the metabolic and cardiovascular benefits that result from a sensible exercise program can greatly improve the quality of life for most diabetic patients. PMID- 1614933 TI - Acute myocardial infarction. An updated protocol for thrombolytic therapy. AB - Only a small percentage of patients who have acute myocardial infarction receive the benefit of intravenous thrombolytic therapy, often because logistics result in unnecessary pre-hospital and in-hospital delays. Dr Selig therefore recommends that a streamlined protocol be available and that it be updated at regular intervals to ensure that this time-dependent therapy is more routinely utilized. PMID- 1614934 TI - The hypertensive patient. Not just a number. AB - Treatment of both systolic-diastolic and isolated systolic hypertension in patients over age 65 has been shown to decrease subsequent cardiovascular morbidity and mortality. In the European Working Party on High Blood Pressure in the Elderly study, the number of morbid and mortal cardiovascular events prevented in the treatment group was 29/1,000 person-years, whereas in the Systolic Hypertension in the Elderly Program, the number was 55/1,000 person years. This magnitude of reduction is substantial, but in the case of primary prevention in the elderly, a large number of patients must be treated to benefit relatively few. Better strategies of targeting treatment based on risk over and above that of high blood pressure are needed. Certainly, patients with more than one cardiovascular risk factor or evidence of end-organ damage should be treated more aggressively. PMID- 1614935 TI - Post-polio syndrome. An emerging threat to polio survivors. AB - The manifestations of post-polio syndrome typically occur 20 to 40 years after an acute episode of poliomyelitis and are confined to previously affected muscles. Because of motor unit remodeling and direct mechanical damage, weakness increases in individual muscles until it exceeds their narrow margin of reserve and becomes clinically apparent. Although the exact cause is not clear, generalized weakness often occurs when several muscles are affected and various postural limb strategies used by the patient are no longer able to compensate for the loss of muscle strength. The mainstays of treatment are life-style changes to avoid overexertion and use of light-weight orthoses and assistive aids to unload the extremities. Exercise and surgery have a limited role in management. PMID- 1614936 TI - How useful are implantable cardioverter-defibrillators? AB - When use of an implantable cardioverter-defibrillator (ICD) is being considered for a patient with life-threatening ventricular arrhythmias, the potential risks and benefits must be carefully weighed. The risks of implantation of an ICD should be minimal; however, a low risk is highly dependent on patient selection and other factors, and perioperative risk varies significantly from center to center. The referring physician should not hesitate to ask for perioperative mortality statistics from the referral center. The difficulty in successfully documenting the usefulness of the ICD is especially important today. As the ICD becomes more like the pacemaker, there will be a natural tendency to expand the use of this new technology to patients in lower-risk groups. Suboptimal methods were adequate to document the benefit of the ICD in high-risk patients, but similar methods may not be adequate for low-risk patients. Fortunately, the importance of performing adequate studies has been recognized, as evidenced by the several randomized controlled trials that have been undertaken to study the efficacy of the ICD in these new groups of patients. PMID- 1614937 TI - Shortage of primary care physicians. PMID- 1614938 TI - Readers respond to CLIA. PMID- 1614939 TI - Readers respond to CLIA. PMID- 1614940 TI - Wheat middlings as an alternative feedstuff for laying hens. AB - Three long-term experiments were conducted to evaluate the possibility of using wheat middlings (WM) for laying hens and to study the responses of six strains of commercial laying hens fed WM diet. In Experiment 1,320 layers maintained in floor pens were fed diets containing 45% WM with .25 or .75% salt, or 89% WM with .25% or 1.5% salt. Salt supplementation did not show any beneficial effect on egg production. Hen-day egg production by hens fed the 45% WM diet was significantly higher for hens fed 45% WM than for those fed the 89% WM diet (79 versus 67.5%, 44-wk period). Feed, limestone, and water intakes were increased by the 89% WM diet. Yolk color, Haugh units, hen livability, and reproductive parameters were not different among the dietary treatments. In Experiments 2 and 3, laying hens from six commercial strains (four strains each experiment, 240 hens per strain) were maintained in laying cages in each year, and fed either a corn and soybean meal (CSM) or a 25% WM diet. Results show that neither diet nor strain had effects on hen-day egg production; however, egg weights from Strains A, C, and F were heavier than those from Strains B, D, and E. Feed intakes and feed utilizations were similar among the s trains. The 25% WM diet increased egg weight, feed intake, and feed utilization compared with the CSM diet. Livability of hens was 93.8 to 97.5% and was not affected by either strain or diet. It is concluded that commercial strains of laying hens can be fed diets containing 25 to 45% WM and still have normal hen-day egg production although feed utilization will be poorer. PMID- 1614941 TI - Glucagon-induced desensitization of broiler adipocyte lipolysis. AB - Continuous exposure of cells to a hormonal stimulus results in attenuation of the hormone's effects on the cell; a process known as desensitization. The present study was undertaken to determine whether glucagon (GLU) induces desensitization of its lipolytic effect in adipocytes isolated from the abdominal fat of market age broilers. Preincubation of adipocytes with 10 to 100 ng/mL of porcine GLU (pGLU) or chicken GLU (cGLU) for 24 h reduced (P less than .05) GLU-stimulated lipolysis. However, pGLU decreased (P less than .05) lipolysis to a greater extent than cGLU. Maximal lipolysis was reduced 70% by pGLU and 55% by cGLU. Chicken GLU also exhibited lower biological potency for acutely stimulating lipolysis from control and cGLU-treated adipocytes. Glycerol release from control adipocytes incubated for 1 h with .3 ng/mL of cGLU or pGLU was 26 and 42 nmol/h per 3% cells, respectively. The GLU-induced decrease in lipolysis occurred rapidly and was partially reversible. The results of the present study indicated that GLU induced desensitization of its lipolytic effect in broiler adipocytes. PMID- 1614942 TI - Effect of inorganic phosphate source and dietary phosphorus level on laying hen performance and eggshell quality. AB - Two experiments were conducted to evaluate laying hen performance when fed two sources of inorganic phosphorus. In Experiment 1, a regular and a coarse form of defluorinated phosphate and one source of dicalcium phosphate were used in diets calculated to contain either .4 or .5% total phosphorus (.2 or .3% nonphytate phosphorus). In Experiment 2, either the regular form of defluorinated phosphate or the dicalcium phosphate source was fed in diets calculated to contain either .4, .5, .6, or .7% total phosphorus (.2, .3, .4, or .5% nonphytate phosphorus). In Experiment 1, hens fed .5% total dietary phosphorus consumed more feed and produced heavier eggs (P less than or equal to .05). Hens fed the .4% dietary phosphorus level lost more weight during the experiment (P less than or equal to .05). No differences among dietary treatments existed for egg specific gravity. A significant source by level interaction occurred for the farm classification of thin-shelled, cracked, or broken eggs and for the total of these classifications. In Experiment 2, egg production, feed consumption, egg weight, and egg mass were depressed (P less than or equal to .05) at the .4% total dietary phosphorus level. Hens fed the .4 and .7% total dietary phosphorus level laid eggs with the highest and lowest egg specific gravity, respectively. This trend was inverse to the effect of these phosphorus levels on egg weights. A significant source by level interaction occurred for the farm classification of thin shell and for the total percentage of eggs with exterior defects. At the .4% total phosphorus level, the regular form of defluorinated phosphate produced eggs with a significantly greater thin shell classification than the dicalcium phosphate source. Hens fed the dicalcium phosphate source produced a higher percentage of compressed-sided and misshapen eggs. PMID- 1614943 TI - Effect of feeding palmitic, oleic, and linoleic acids to Japanese quail hens (Coturnix coturnix japonica). 2. Maternal diets and stage of incubation on the lipid metabolism of quail embryos. AB - An experiment was conducted to evaluate the effects of diets containing 3% of either palmitic acid (Diet PA), oleic acid (Diet OA), or linoleic acid (Diet LA) and three stages of development (Days 11, 13, and 15 of incubation) on 1) weights of yolk plus yolk sac membrane (TY), yolk sac membrane (YSM), yolk, liver, and extrahepatic tissue (ET); and 2) the fatty acid composition of phospholipid, triglyceride, and cholesterol ester fractions of YSM and ET of quail embryos. Embryos from birds fed Diet LA had the highest (P less than .05) weights of TY and yolk followed by those from birds fed Diet OA and Diet PA. The weight of ET was highest (P less than .05) in embryos from birds fed Diet PA followed by those from birds fed Diet LA and Diet OA. The weights of YSM and liver were not affected by the maternal diet (P greater than .05). The weight of TY decreased whereas the weights of liver and ET increased as incubation progressed (P less than .05). The weight of YSM was maximum at Day 13 of incubation. In the phospholipid, triglyceride, and cholesterol ester fractions of both YSM and ET of embryos, the fatty acid present at the highest level, except palmitic acid, was the one added to the maternal diet. In phospholipids of both YSM and ET the oleic acid content decreased and linoleic acid increased as incubation progressed. In triglycerides and cholesterol esters of both YSM and ET, the levels of palmitic acid increased, but oleic and linoleic acids decreased, with advancing embryonic development. The results of the present study indicate that embryos from birds fed Diet PA mobilize more yolk material and produce heavier ET than embryos from birds fed Diet OA and Diet LA. The fatty acid profiles of phospholipid, triglyceride, and cholesterol esters of embryonic tissues are consistently influenced by dietary fatty acid and the stage of development. PMID- 1614944 TI - Mineral balance and urinary and fecal mineral excretion profile of broilers housed in thermoneutral and heat-distressed environments. AB - Two experiments were conducted utilizing 4- to 7-wk posthatching Vantress x Arbor Acres male broilers to evaluate heat distress effects on mineral balance partitioned into urinary and fecal loss. In the first study, 8 colostomized and 14 intact birds were allotted to two environmental chambers maintained at either a thermoneutral temperature (24 C) or a cycling temperature heat distress (24 to 35 C) in a switch-back design. Birds were precision-fed 2% of body weight thrice daily to equalize consumption prior to and over each 48-h experimental period. Feces and urine for colostomized birds and total excrement for intact birds were collected and analyzed for mineral content. Averaging across surgical classification, heat distress increased (P less than .05) excretion of K, P, S, Mg, Cu, Mo, and Zn. Despite little heat distress effect on urine production, minerals disproportionately excreted in urine included K, Mg, P, and S; Cu and Mg were lost primarily in feces. In the second study 42 colostomized birds were used to expand the urinary excretion data with the period of heat distress held at 35 C for 36 h. Heat distress increased (P less than .05) urine output from 52.3 +/- 5.3 to 109.9 +/- 4.5 mL/12 h and also increased total urinary K, P, S, Na, Mg, Ca, and Mn excretion. The present data provide evidence that heat distress adversely impacts bird mineral balance and that the excretion route for this effect varies with the specific mineral and possibly, heat distress severity. PMID- 1614945 TI - Changes in plasma catecholamine, free fatty acid, and glucose concentrations, and plasma monoamine oxidase activity before and after feeding in laying hens. AB - In order to better understand the relationship of free fatty acid (FFA) concentrations to feed intake in laying hens, plasma levels of catecholamine, glucose, and FFA and plasma monoamine oxidase activity were measured. Blood samples were taken in the morning before and after the start of feeding via chronic brachial vein catheters. Plasma concentrations of epinephrine and norepinephrine were analyzed by modified HPLC with an electrochemical detection method. Plasma concentrations of FFA and glucose were not significantly different before and after the start of feeding, however a negative correlation (r = -.763, r2 = .582, P less than .01) between these parameters was observed. No significant correlations between the plasma concentration of FFA and plasma concentrations of epinephrine or norepinephrine before and after the start of feeding were observed. However these were significantly correlated (r = .444, r2 = .197, P less than .05 for FFA and epinephrine; r = .787, r2 = .619, P less than .01 for FFA and norepinephrine) when the behavioral activity of hens was low, such as in resting or feeding. Plasma activity of monoamine oxidase was not different before and after the start of feeding, and no relationship was observed between plasma monoamine oxidase activity and plasma epinephrine or norepinephrine concentration. It is suggested that the increase in plasma FFA concentration before feeding would be elicited by the increase in the circulating epinephrine and norepinephrine concentrations. Plasma FFA concentration was not affected by the increase in circulating epinephrine and norepinephrine concentrations during active behavior such as pacing and egg call before and after oviposition. PMID- 1614946 TI - Response to angiotensin II after selective lesioning of brain regions believed to be involved in water intake regulation. AB - The subfornical organ (SFO) and organum vasculosum lamina terminalis (OVLT) are regions of the brain that border the third ventricle (outside the blood-brain barrier) and have been implicated in the control of water intake elicited by angiotensin II (ANGII). Studies were conducted in which the response to injected ANGII following lesions of the SFO (LSFO) or OVLT (LOVLT) in broiler chicks was observed. Three groups of birds were used for each trial: lesioned and ANGII injected (LI); not lesioned and ANGII-injected (NLI); and not lesioned and saline injected (NLC). In Experiment 1, water intake of LISFO was decreased through 3 h postinjection (P less than .01). Intakes of LISFO and NLCSFO were not significantly different through 1 h postinjection. The OVLT did not have an effect on cumulative water intake in response to intramuscular ANGII. Water intakes of LIOVLT and NLIOVLT did not differ from each other, but were significantly higher than NLCOVLT (P less than .05) at .5 and 1 h postinjection. Feed intake was unaltered by SFO or OVLT lesions. Feed intake was suppressed and water intake increased by ANGII injection. The present study indicates that the SFO, but not the OVLT, plays a role in ANGII-induced water intake in broiler chicks. PMID- 1614947 TI - Research note: effect of 2,4-dinitrophenol on growth and body composition of broilers. AB - The effects of 2,4-dinitrophenol (DNP) on growth, feed efficiency, fattening, and mitochondrial functions of liver and skeletal muscle were studied in broilers. The DNP was added at levels of 100, 200, and 400 mg/kg of diet. Feed intake was not changed with administration of DNP except at 100 mg/kg of diet. Body weight was significantly decreased by administration of DNP at 400 mg/kg of diet compared with those at 0 and 100 mg/kg of diet. Feed efficiency was significantly reduced by administration of DNP at 400 mg/kg of diet. Abdominal fat and carcass fat contents, expressed either as absolute values or relative percentages of body weight, were significantly decreased with increasing dietary DNP concentration above 200 mg/kg of diet. These results showed that administration of DNP reduced body fat, which may be associated with the change in feed efficiency. No reduction in adenosine triphosphate:oxygen ratio with increasing DNP concentration was observed in hepatic and skeletal muscle mitochondria isolated from broilers fed experimental diets containing DNP. PMID- 1614948 TI - Research note: broiler acclimation to heat distress and feed intake effects on body temperature in birds exposed to thermoneutral and high ambient temperatures. AB - Relationships between ambient temperature, bird acclimation to cycling temperature, heat distress, and feed consumption were evaluated in two experiments. In the first experiment, birds previously acclimated to cycling temperature heat distress (24 to 35 C) for two 24-h cycles were observed to have 24% lower (P less than .01) feed consumption than birds previously housed at 24 C and experiencing their first heat distress exposure. A significant (P less than .01) acclimation history by ambient temperature interaction was detected, with acclimated birds having a higher rectal temperature (42.3 versus 41.2 C) when housed at 24 C and a lower rectal temperature (44.2 versus 44.6 C) when exposed to 35 C than did the unacclimated controls. In the second experiment, feed intake and acclimation effects were separated by precision-feeding birds 0, 5, and 10% of body weight. Rectal temperature in the 24 C and 35 C environments increased linearly (P less than .01) as feeding level increased for both acclimated and unacclimated birds. Similar to the first experiment, an ambient temperature by acclimation history interaction was detected (P less than .01), with acclimated birds exhibiting increased body temperature when housed in thermoneutral environments and lower body temperature when exposed to high ambient temperature distress.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614949 TI - Effect of light intensity level during prelay light restriction on subsequent reproductive performance of turkey breeder hens. AB - Two trials were conducted to determine whether light intensity levels during the prelay (light restriction) and the lay (egg production) periods influenced subsequent photoinduced reproductive performance of turkey breeder hens. The light intensity levels were 22 and 270 lx and each was provided during the prelay and lay periods in a factorial arrangement. Each of the period light intensity levels were applied to half of the hens from each prelay treatment group. Data were collected for BW, rate of reproductive development, egg production, fertility, hatchability, egg weight, and poult weight. There were no interactions between the prelay and lay period treatments, nor a consistent prelay light intensity effect on rate of initiation of lay or duration of time to achieve 50% production. In addition, prelay and lay light intensity levels had no consistent effects on rate of lay, percentage of fertility and hatchability, egg weight, and poult weight. It was concluded that there was no advantage to the use of high intensity light during short-day light restriction of the prelay period on subsequent reproductive performance. PMID- 1614951 TI - Effect of periodic feeding and photoperiod on anticipation of feed withdrawal. AB - Broiler chicks obtained from a commercial hatchery were reared on litter in environmental chambers. The rearing temperature was 32 C initially, and reduced 2,8 C/wk until 24 C was reached. Water was available for ad libitum intake. The treatments began at 7 days in Trial 1 and at 8 days in Trial 2, during which feed and water consumption were recorded by computer every 30 min and summarized for 2 and 24-h periods until each trial was completed. In Trial 1, the treatments were: 1) continuous light with feed available 12 h/day; and 2) 12 h light (L):12 h dark (D) with feed available for ad libitum consumption for 1 wk and unavailable thereafter during darkness. In Trial 2, the treatments were 1) 14L:10D; 2) 10L:14D; and 3) continuous light. During the treatments, no feed was provided during darkness and only for 12 h/day during continuous light. At 29 days, feeding and lighting were again continuously provided until the trial ended at 33 days. Broilers were able to anticipate the period of feed unavailability when it coincided with darkness. They were unable to anticipate the period when feed was unavailable if they were in continuous light. Continuously lighted broilers consumed more feed at the onset of the feeding period than did the broilers in light:dark cycles. Periodically lighted broilers consumed more feed at the end than at the onset of the feeding period. Resumption of continuous feeding occurred more quickly for continuously lighted broilers than for those previously on light:dark cycles. The data indicate that the internal clock that permits broilers to anticipate recurring periods of feed unavailability depends on a daily period of darkness. PMID- 1614950 TI - Laying hen performance as affected by diet and caging density. AB - Two trials were conducted to investigate the effects of caging density and diet on the performance of caged layers. Diets were formulated contain .775, .725, and .675% lysine. The TSAA content was formulated to be 85% of the lysine content of each diet. Pullets were caged in 25.4 cm wide x 40.0 cm deep cages at three, two, or one bird per cage. Production data were collected for 112 days in Trial 1 and 168 days in Trial 2. As dietary protein, lysine, and TSAA increased, hen-day egg production, egg weight, and feed conversion improved (P less than .05) . Feed consumption and feed per dozen eggs were not consistently affected by diet. Caging density had no consistent effects on any of the production parameters. No interactions were detected between dietary treatments and cage density in either trial. PMID- 1614952 TI - Barley inclusion and avoparcin supplementation in broiler diets. 1. Effect on small intestinal bacterial flora and performance. AB - Diets based on barley or corn without avoparcin supplementation were associated with high counts of Clostridium perfringens in the contents of the small intestine of the birds at the age of 2 to 4 wk. The weight gain of birds younger than 2 wk and the body weight of 4-wk-old birds were significantly lower, and the feed conversion ratio at slaughter was significantly higher, in birds on barley diets than in birds on corn diets. The frequency of birds with sticky droppings on Day 21 was significantly higher for barley diets. The number of C. perfringens, and the feed conversion ratio at slaughter were significantly lower but the number of coliform bacteria, weight gain during the 3rd wk, and body weight of 4-wk-old chickens were significantly higher when the diets were supplemented with 7.5 mg avoparcin/kg feed. The effect of avoparcin on the feed conversion ratio was statistically significant only on a barley diet. PMID- 1614953 TI - Effect of monensin on ultrastructure and cellular invasion by the turkey coccidia Eimeria adenoeides and Eimeria meleagrimitis. AB - Freshly excysted sporozoites (SZ) of the turkey coccidia Eimeria meleagrimitis and Eimeria adenoeides were incubated at 41 C in concentrations of monensin from .01 to 1.0 microgram/mL, washed free of the drug, and either processed for phase, fluorescence, and transmission electron microscopy or inoculated into cultures of turkey kidney cells. Phase microscopy indicated that after 1.5 h incubation in 1.0 micrograms/mL monensin, about 60% of the SZ of E. meleagrimitis had become notably rounded or displayed localized protrusions. These alterations were accompanied by ultrastructural abnormalities (in 90% of the SZ) including vacuoles in the cytoplasm, bulging and separation of plasma membrane layers, and dense bands in the refractile bodies that extended toward the periphery of the refractile body. Similar morphological and ultrastructural changes were observed in over half of the E. adenoeides SZ after 2 h incubation in 1.0 micrograms/mL monensin. Additionally, some specimens contained a pycnotic nucleus that was usually surrounded by a large vacuole. After 4 h incubation, almost all of the SZ displayed some degree of ultrastructural damage. Indirect fluorescent antibody labeling with parasite-specific monoclonal antibodies demonstrated clouds of antigen surrounding the monensin-treated but not the untreated SZ, suggesting an increase in permeability with incubation in monensin. With both E. meleagrimitis and E. adenoeides, the structural changes were reflected in a significant inhibition of cellular invasion. The inhibitory activity of monensin was concentration- and time-dependent in that the greatest inhibition of invasion was observed in SZ incubated for 4 h in 1.0 micrograms/mL of monensin; shorter incubation times or lower concentrations of monensin having less effect. PMID- 1614954 TI - Comparison of heat-shock-induced and lipopolysaccharide-induced protein changes and tumoricidal activity in a chicken mononuclear cell line. AB - The functions of a chicken mononuclear phagocytic cell line MQ-NCSU were examined after exposure to nonthermal (lipopolysaccharide, LPS) and thermal (heat shock, HS) treatments. The protein profiles and tumoricidal factor activity of MQ-NCSU cells exposed to 15 micrograms LPS under control (41 C) temperatures expressed enhanced synthesis of classical 23-, 70-, and 90-kDa HS proteins (HSP), a heat inducible 32-kDa protein (P32), and a novel LPS-induced 120-kDa protein (P120). In comparison to LPS treatment, MQ-NCSU cells exposed to 45 C (HS) expressed HSP23, HSP70, HSP90, and P32 but not P120. Combined exposure of MQ-NCSU cells to HS (45 C) and LPS (15 micrograms) induced an alteration in the initial and optimal expression and duration of synthesis of the HSP and the LPS-induced P120. The tumoricidal activity of supernatants from LPS-treated and untreated MQ-NCSU cells cultured at 45 C was significantly depressed as compared with the controls (cultured at 41 C). The supernatants collected from LPS-treated and untreated MQ NCSU cultures maintained at 41 C were exposed to 45 C temperature for up to 48 h. The tumoricidal potential of these supernatants was not affected. The present study demonstrates that LPS exposure induces several "stress" proteins in macrophages, some of which have molecular similarity with the classical HSP. In addition, LPS induces a unique 120-kDa protein not produced following HS alone, which may serve as a differential protein associated with activated or tumoricidal phenotype of macrophages. Heat shock suppresses the tumoricidal potential of LPS-treated MQ-NCSU cells in a regulatory manner that does not appear to be a result of thermal denaturation of the tumoricidal factor secreted in the culture supernatant. PMID- 1614955 TI - Heat-shock protein synthesis in chicken macrophages: influence of in vivo and in vitro heat shock, lead acetate, and lipopolysaccharide. AB - Synthesis of heat-shock proteins (HSP) in chicken macrophages, in response to thermal and nonthermal stressors, was determined. Cornell K-strain 6-wk-old White Leghorn females were injected with Sephadex and approximately 42 h later subjected to elevated temperatures in order to achieve a core body temperature (CBT) of 44 C. Peritoneal macrophages were isolated at 30 and 60 min after heat treatment. A parallel group of chickens, maintained at the normal CBT of 41 C, was used as controls and peritoneal macrophages were isolated after 60 min of treatment. For in vitro study of HSP response, cells of a chicken macrophage cell line (MQ-NCSU) were subjected to 45 C ambient temperature to produce heat shock (HS, thermal stress), lipopolysaccharide (LPS, 15 micrograms), and lead acetate (nonthermal stress) exposure for varying time periods. The HSP profiles of macrophages following various treatments were determined by one- and two dimensional gel electrophoresis. The results showed that macrophages isolated from the 44 C CBT group synthesized HSP90, HSP70, HSP23, and a heat-inducible P32 protein. This HSP synthesis profile was similar to the HSP expression by MQ-NCSU cells exposed in vitro to 45 C conditions. Exposure to MQ-NCSU cells to lead acetate induced the same four proteins previously expressed by macrophages after in vivo or in vitro heat treatment. Two-dimensional analysis of lysates from cells treated with LPS, HS, or LPS plus HS treatments revealed a doublet protein molecule (70a and 70b) with identical molecular mass of 70 kDa. However, the pI value (isoelectric point) of 70b was higher (5.1) than that of 70a, which, along with HSP90 and HSP23, focused more toward the acidic side with a pI value of less than 4.6. The present study is the first to report pI profiles of chicken macrophage HSP. The in vitro and in vivo studies suggest that chicken macrophages respond to thermal and nonthermal stressors by producing similar kinds of "stress proteins". PMID- 1614956 TI - 81st annual meeting of the Poultry Science Association, Inc., Fayetteville, Arkansas, August 3-6, 1992 and 13th annual meeting of the Southern Poultry Science Society, Atlanta, Georgia, January 20-21, 1992. Abstracts. PMID- 1614957 TI - Hydrogels: swelling, drug loading, and release. AB - Hydrogels have been used by many investigators in controlled-release drug delivery systems because of their good tissue compatibility and easy manipulation of swelling level and, thereby, solute permeability. The desired kinetics, duration, and rate of solute release from hydrogels are limited to specific conditions, such as hydrogel properties, amount of incorporated drug, drug solubility, and drug-polymer interactions. This review summarizes the compositional and structural effects of polymers on swelling, loading, and release and approaches to characterize solute release behavior in a dynamic state. A new approach is introduced to compensate drug effects (solubility and loading) with the release kinetics by varying the structure of heterogeneous polymers. Modulated or pulsatile drug delivery using functional hydrogels is a recent trend in hydrogel drug delivery. PMID- 1614958 TI - Pharmacokinetic/dynamic correlation of pulmonary and cardiac effects of fenoterol in asthmatic patients after different routes of administration. AB - Pulmonary and cardiac effects of the beta 2-adrenergic drug fenoterol were studied in 27 asthmatic patients using an integrated pharmacokinetic/dynamic (PK/PD) approach. Airway resistance (Rf), intrathoracic gas volume (IGV), heart rate, and plasma levels were monitored after placebo, injection (12.5 and 25 micrograms), nasal instillation (400 micrograms), inhalation (200 and 400 micrograms), and infusion (200 micrograms/180 min with or without loading dose). The pharmacokinetics were best described by an open three-compartment model with a terminal half-life of 200 min (gamma = 0.23 +/- 0.08 L/hr), a volume of distribution at steady state of 1.9 +/- 0.8 L/kg, and a clearance of 0.86 +/- 0.32 L/hr/kg, with 14 and 9% absorbed after nasal and pulmonary administration, respectively. For the noninhalation regimens, a PK/PD correlation linked the concentration in the shallow pharmacokinetic compartment to the investigated effects via an Emax relationship, resulting in three to five times higher EC50 values (concentration necessary to achieve half-maximal effect) for the heart rate than for the beta 2-mediated effects on IGV and Rf. In contrast, pulmonary effects after inhalation could not be incorporated into the correlation, indicating that these effects are induced locally after inhalation. Intrapatient variability for EC50 and Emax was approximately 90%. PMID- 1614959 TI - The bilayer floating capsule: a stomach-directed drug delivery system for misoprostol. AB - A bilayer floating dosage unit is proposed to achieve local delivery of misoprostol, a prostaglandin E1 analogue, at the gastric mucosa level. The system is a capsule consisting of a floating layer maintaining the dosage unit buoyant upon the gastric content and a drug layer formulated to act as a sustained delivery system. The differential design of the two layers allows the optimization of both floating capability and drug release profile. The layers are both composed of a hydrophilic matrix based upon hydroxypropylmethyl cellulose (HPMC). Parameters influencing the release profiles are described. The use of a large capsule increases the gastric residence time (GRT), as it impedes passage through the pylorus opening. gamma-Scintigraphic studies were performed to visualize cohesion of the two layers in vivo and to determine GRT as a function of meal regimen. The average GRTs were 199 +/- 69 min after a single meal (breakfast) and 618 +/- 208 min after a succession of meals. PMID- 1614960 TI - Cutaneous metabolism of nitroglycerin in vitro. II. Effects of skin condition and penetration enhancement. AB - The effects of skin storage, skin preparation, skin pretreatment with a penetration enhancer, and skin barrier removal by adhesive tape-stripping on the concurrent cutaneous transport and metabolism of nitroglycerin (GTN) have been studied in vitro using hairless mouse skin. Storing the skin for 10 days at 4 degrees C did not alter barrier function to total nitrate flux [GTN + 1,2 glyceryl dinitrate (1,2-GDN) + 1,3-glyceryl dinitrate (1,3-GDN)]. However, metabolic function was significantly impaired and suggested at least fivefold loss of enzyme activity. Heating skin to 100 degrees C for 5 min appreciably damaged hairless mouse skin barrier function. The ability to hydrolyze GTN was still present, however, and remained constant over the 10-hr experimental period, in contrast to the "control," which showed progressively decreasing enzymatic function with time. Pretreatment of hairless mouse skin in vivo (prior to animal sacrifice, tissue excision, and in vitro transport/metabolism studies) with 1 dodecylazacycloheptan-2-one (Azone), a putative penetration enhancer, significantly lowered the skin barrier to nitrate flux (relative to the appropriate control). Again, barrier perturbation resulted in essentially constant metabolic activity over the observation period. The ratio of metabolites formed (1,2-GDN/1,3-GDN) was increased from less than unity to slightly above 1 by the Azone treatment. Adhesive tape-stripping gradually destroyed skin barrier function by removal of the stratum corneum. The effects of 15 tape-strips were identical to those of Azone pretreatment: a greatly enhanced flux, a constant percentage formation of metabolites over 10 hr (once again), and an increase in the 1,2-GDN/1,3 GDN ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614961 TI - Rotating-disk dissolution kinetics of nitrofurantoin anhydrate and monohydrate at various temperatures. AB - The dissolution behavior of nitrofurantoin anhydrate and monohydrate in JP XI, second fluid (pH 6.8) was investigated at various temperatures using a dispersed amount method and a rotating-disk method. The initial dissolution process of the monohydrate obtained by the rotating-disk method followed the Noyes-Whitney Nernst equation, but that of the anhydrate did not. The initial dissolution process of the anhydrate was analyzed by a dissolution kinetics equation involving the phase transformation process from anhydrate to monohydrate. The maximal concentration, the dissolution rate constant, and the rate constant of the phase transition process were estimated. The thermodynamic parameters for the dissolution processes of the anhydrate and monohydrate were obtained from van't Hoff plots and Arrhenius plots, respectively. The results of the intrinsic solubility and dissolution parameters of anhydrate and monohydrate suggest the possibility that the difference in the dissolution rates of the anhydrate and monohydrate affect the bioavailability of nitrofurantoin preparation. Information on the dissolution behavior of nitrofurantoin pseudopolymorphs is therefore useful for designing high-quality preparations. PMID- 1614962 TI - An electrically modulated drug delivery device. III. Factors affecting drug stability during electrophoresis. AB - A number of factors affecting the stability of propranolol HCl during electrophoretic control were investigated. It was found that significant degradation of propranolol HCl and hydrolysis of water occurred when a current of 15 mA was used with platinized electrodes. This degradation was thought to be due to decomposition of propranolol HCl at the electrodes. Degradation could be significantly reduced by using uncoated platinum electrodes and currents in the range of 0 to 2.5 mA, while still allowing control of drug delivery rates. Electrode reaction processes were found at high ionic strengths and high drug concentrations but were not thought to be associated with drug decomposition. PMID- 1614963 TI - Simultaneous in vitro measurement of intestinal tissue permeability and transepithelial electrical resistance (TEER) using Sweetana-Grass diffusion cells. AB - A simple modification of the commercially available Sweetana-Grass (S-G) side-by side diffusion cells, allowing the simultaneous measurement of tissue permeability and transepithelial electrical resistance (TEER), has been described and validated for rat excised, muscle-free intestinal tissue. The TEER-lowering effects of a series of acylcarnitines were shown to be correlated with previously reported in vitro (i.e., membrane perturbation) and in vivo (i.e., absorption enhancement) activity. The TEER-lowering effect of palmitoyl carnitine chloride (PCC) was also shown to be reversible. The effects of PCC on TEER and the permeability of poorly absorbed compounds (cefoxitin and lucifer yellow) were simultaneously determined. Compared to controls (mannitol-treated), PCC immediately produced a rapid drop in colon TEER. By 5 min post-PCC addition, colon TEER was 50% of control; by 10 min post-PCC addition, colon TEER was 17% of control. After a lag of about 5-10 min post-PCC addition, the cefoxitin or lucifer yellow permeability coefficient increased more than 20-fold. The modified S-G cells provide a simple and reproducible method whereby flux and TEER can be simultaneously determined, providing a valuable link between the effect of absorption enhancers on TEER measurements and the increased permeability of poorly absorbed compounds. PMID- 1614964 TI - Intestinal absorption of peptides and peptide analogues: implications of fasting pancreatic serine protease levels and pH on the extent of oral absorption in dogs and humans. AB - In order to describe and predict the impact of intestinal metabolism on peptide absorption, intestinal chymotrypsin activity, flow rate, and pH were characterized in fasted, duodenally fistulated dogs as a function of gastrointestinal (GI) motility phase. GI motility was classified as either active or quiescent. Cumulative volume, F(t), and volumetric flow rate, Q(t), curves were constructed and the data were sorted according to motility phase. The mean +/- SE active phase pH was 6.4 +/- 0.3, whereas the quiescent phase pH was 7.3 +/ 0.3. The difference between the mean active and the mean quiescent phase pH values was significant. The active and quiescent phase flow rates (ml/min) were also significantly different, at values of 1.2 +/- 0.2 and 0.28 +/- 0.07, respectively. The active phase flow rates were consistent among the dogs studied; however, the quiescent phase flow rates were highly variable among the dogs. The variability of the quiescent phase flow rates was expected since phase II of the GI motility cycle is characterized by intermediate, irregular spike activity. The mean active and quiescent phase chymotrypsin activities were 1.87 x 10(-5) +/- 0.53 x 10(-5) and 1.56 x 10(-5) +/- 0.65 x 10(-5) M, respectively. The active phase values were not statistically different among dogs, however, the quiescent phase values were found to be highly variable among dogs. The difference between the active and the quiescent phase chymotrypsin mean levels, however, was not statistically significant. The chymotrypsin levels determined in dogs were found to be approximately 10 times greater than those reported in humans.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614965 TI - Mechanism and site dependency of intestinal mucosal transport and metabolism of thymidine analogues. AB - This study has been undertaken to investigate the mechanisms of intestinal mucosal transport and metabolism of thymidine analogues and to identify any optimal site(s) of the rat intestine particularly involved in the absorption of thymidine analogues. The intestinal absorption of 3'-azido-3'-deoxythymidine (AZT) was studied at three initial concentrations in four segments of the rat intestine using an in situ recirculating perfusion technique. Disappearance of AZT followed first-order kinetics throughout the gastrointestinal (GI) tract at all tested concentrations. The apparent first-order rate constants were found to be relatively invariant over a broad range of concentrations from 0.01 to 1.0 mM. Corrected for the length of each segment, the apparent permeability (Papp) of AZT was 3.01 +/- 0.32 x 10(-5) cm/sec (mean +/- SE) in the duodenum, 2.06 +/- 0.24 x 10(-5) cm/sec in the upper jejunum, 0.76 +/- 0.13 x 10(-5) cm/sec in the combined lower jejunum and ileum, and 0.32 +/- 0.10 x 10(-5) cm/sec in the colon, which indicated that intrinsic absorptivity was greater in the upper GI tract than in the lower portions possibly due to the differences in surface area for absorption. No AZT metabolite appeared in any part of the GI tract. On the other hand, thymidine and other analogues, i.e., 5-iodo-2'-deoxyuridine and 2' deoxyuridine, were rapidly metabolized into nucleobase and sugar in the upper GI tract, whereas in the colon no metabolite appeared. A free 3'-OH group appears to be necessary for the metabolism (catabolism) of thymidine analogues in the rat intestine mainly by pyrimidine nucleoside phosphorylase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614966 TI - Analysis of zidovudine distribution to specific regions in rabbit brain using microdialysis. AB - The distribution of zidovudine (3'-azido-3'-deoxythymidine; AZT) into two regions of rabbit brain was investigated in crossover using microdialysis. Six rabbits had guide cannulas surgically implanted in the lateral ventricle and thalamus by stereotaxic placement. After recovery, microdialysis probes were positioned and i.v. bolus doses of 5, 10, 20, and 30 mg/kg were administered to each animal over a period of 2 weeks. Blood was drawn via a marginal ear vein catheter for 8 hr. Brain dialysate was collected at 3 microliters/min from ventricle and thalamus dialysis probes every 10 min. Simulated cerebrospinal fluid (CSF), to which 3' azido-2',3'-dideoxyuridine (AZdU) was added, was used as perfusate. AZdU loss, which was measured during simultaneous retrodialysis, served as a marker for in vivo recovery of AZT. AZT concentrations in plasma, as well as in ventricle and thalamus dialysate, were determined using a sensitive HPLC assay, and AZdU was simultaneously analyzed in the dialysates. Calculation of in vivo recovery of AZT was based on loss of AZdU from the perfusate during retrodialysis and was used to estimate the concentration of drug at both sites in the brain. In vitro loss of AZdU and recovery of AZT showed good agreement, demonstrating a bivariate regression slope of 0.99. The half-lives and AUCs (normalized to dose) achieved in the plasma, ventricle, or thalamus were not significantly different for the four doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614967 TI - Uptake and stereoselective binding of the enantiomers of MK-927, a potent carbonic anhydrase inhibitor, by human erythrocytes in vitro. AB - MK-927 [5,6-dihydro-4H-4(isobutylamino)thieno(2,3-B)thiopyran -2-sulfonamide-7.7 dioxide], a potent carbonic anhydrase inhibitor, contains a chiral center and exists as a racemate. In order to understand the kinetic behavior of the enantiomers of MK-927 in the body, the uptake and binding of these compounds were studied in human erythrocytes in vitro. Since no degradation or metabolism of the enantiomers occurred during incubation in blood, one can describe the equilibration of the drugs between plasma and erythrocytes by a closed two compartment system. Erythrocytes were considered as a compartment composed of two parts: one in which free drug is exchangeable to plasma and the other in which drug is tightly bound to carbonic anhydrase in a Michaelis-Menten type binding. After the addition of the enantiomers individually to fresh blood, they were taken up by erythrocytes rapidly in a concentration-dependent manner. The time to achieve equilibrium decreased as the concentration increased, suggesting saturation of binding sites. With the assumption of simple diffusion, the binding and transfer kinetics were determined simultaneously by computer fitting. There were no stereoselective differences in the transfer process of the enantiomers across the erythrocyte membrane, while binding of the enantiomers exhibited stereoselectivity. The penetration of the unbound enantiomer across the erythrocyte cell membrane was rapid, with a mean transit time of about 3 sec. The S-(+)-enantiomer was bound to the high-affinity carbonic anhydrase isoenzyme more strongly than the R-(-)-enantiomer by approximately 10-fold. For the low-affinity isoenzyme, the R-(-)-enantiomer was bound more strongly than the S-(+) enantiomer. PMID- 1614968 TI - Use of a pharmacokinetic model incorporating discontinuous gastrointestinal absorption to examine the occurrence of double peaks in oral concentration-time profiles. AB - Double peaks in the plasma concentration-time profile following oral administration have been reported for several compounds. A pharmacokinetic model incorporating discontinuous absorption was developed to simulate concentration time profiles with double peaks. The gastrointestinal (GI) tract was divided into N compartments, with absorption occurring only from the second and Nth compartments. A two-compartment model was used to describe systemic drug disposition. The effect of gastric emptying and GI transit rate constants (Kl and K1, respectively), number of hypothetical gut compartments, and absorption rate constant at each site (Ka1, Ka2) on the time of occurrence of each peak (Tp1, Tp2), the theoretical fraction of the dose absorbed at each site (phi 1, phi 2), and the contribution of the second site to systemic drug exposure (expressed as phi 2rel) were examined. Simulated concentration-time profiles demonstrated that Tp2 was determined by Kt and N, while Tp1 was determined by K1 and Kt. Changes in Ka1 and Ka2 had no effect on Tp1 or Tp2. phi 1, phi 2, and phi 2rel were determined by Ka1, Ka2, and Kt, and simulations indicated that a secondary peak in the concentration-time profile will be evident only when phi 2rel is substantial. In addition, concentration-time data for ranitidine and cimetidine, which displayed double peaks, were fit with the model. The present model described both data sets well, and realistic pharmacokinetic and physiologic parameters (absorption rate constants, systemic bioavailabilities, GI residence times) were obtained. PMID- 1614969 TI - Bacterial monitoring in vials using a spectrophotometric assimilation method. AB - Aseptic-filling processes are often used with fragile parenteral products that might be destroyed by terminal autoclaving. However, aseptic filling is not as effective as autoclaving in reducing contamination. As a result, time-consuming microbiological methods and turbidimetry are employed currently as product inspection techniques, but these processes can destroy the product and might not detect low levels of contamination. Thus, near-infrared (IR) light scattering was evaluated in this study as a new method for determining low levels of contamination noninvasively and nondestructively. A new parallel mathematical technique was used in conjunction with near-IR spectrophotometry to detect successfully contamination by several species of bacteria through intact glass vials. Using the near-IR method, products can be evaluated without introducing contamination, preserving the sample vial for dispensing or evaluation by another method. PMID- 1614970 TI - New water-soluble pilocarpine derivatives with enhanced and sustained muscarinic activity. AB - The synthesis of an homologous series of new water-soluble derivatives of pilocarpine is described. The new compounds, referred to as soft quaternary salts, are water soluble by virtue of a cationic ammonium head and their lipophilicity can be modulated by manipulating the size and the nature of the substituent in the inactive portion of the molecule. The miotic activity of the compounds was evaluated after administration to normotensive New Zealand White rabbits. Changes in pupil size indicated a substantial cholinergic effect on the iridal sphincter musculature. The best candidate, compound 20, which has a 16 carbon side chain, was evaluated for reduction of the intraocular pressure in genetically glaucomatous Beagles. Compound 20 is superior to pilocarpine in both tests, with a potency 10 to 20 times that of the parent compound and a longer duration of action. It is suggested that the new compounds are prodrug forms of pilocarpine which greatly enhance the corneal bioavailability of the parent compound. PMID- 1614971 TI - The anomalous hydrolytic behavior of 1-phenylvinyl phosphate. AB - The kinetics of hydrolysis of 1-phenylvinyl phosphate, 1, were studied over a pH range of 1 to 8.3 and over a pD range of 1 to 5.6 at 25 degrees C and mu = 0.5 M with sodium chloride. The hydrolytic behavior of 1 was found to differ, in many respects, from that of alkyl and aryl phosphomonoesters. First, the rates of hydrolysis of 1 were extremely rapid and, in the hydronium ion-catalyzed region, gave a solvent deuterium isotope effect (kH/kD) of 3.20. Also, the 1H-NMR spectrum of acetophenone formed upon complete hydrolysis of 1 in D2O (pD 1.2) revealed that only one deuterium atom was incorporated into the methyl group. Hence, the evidence was consistent with a rate-limiting and nonreversible proton transfer from the solvent to 1. In addition, using an H2 18O labeling study in conjunction with 31P-NMR analysis, the hydrolytic mechanism appeared to involve nucleophilic attack by water at both the alpha-carbon and the phosphorus atom with concurrent C-O and P-O bond fission. Second, in the pH region where the monoanionic species of 1 predominated, buffers had a pronounced catalytic effect on the hydrolysis rate; there appeared to be a normal solvent deuterium isotope effect; and the rate constant, k' o, showed a positive deviation from the established Bronsted relationship. The dissimilarities between 1 and alkyl and aryl phosphomonoesters supported the involvement of an alternate dephosphorylation pathway.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1614972 TI - Evaluation of the Poisson distribution for estimating the quality of drug/diluent random powder mixtures. I. High particle size of the drug constituent. AB - Use of the Poisson distribution to estimate the quality of random mixtures was evaluated as a measure of the highest attainable degree of dose uniformity of tablets. Ingredient A was assumed to have a large particle size as compared to diluent B. In contrast to the more precise binomial distribution, for the simple Poisson approach no experiments are necessary to investigate the mean proportions of the apparent volume, av and bv, which A and B assume within the powder samples in the die. The range of volume ratios was defined where the Poisson distribution is valid. Accepting an error of 5% of the random content variation of A per sample, av may amount to up to 0.1 (10%). In terms of the proportion by mass of A, a, this range is wider, and commonly of the order of 0.2 or higher. This approach was tested with tablets prepared from mixtures of coarse sucrose A and a fine Avicel/talc diluent B at A:B (m:m) ratios from 10:90 to 50:50. Even with the 30:70 tablets, the variations of the sucrose content were still in good agreement with the content variations of the random mixtures as estimated from the Poisson distribution. Estimates of the 50:50 ratio, however, deviated from the Poisson distribution. PMID- 1614973 TI - Optimized formulation of magnetic chitosan microspheres containing the anticancer agent, oxantrazole. AB - A combined emulsion/polymer cross-linking/solvent evaporation technique was used to prepare magnetic chitosan microspheres (MCM) containing the anticancer drug, oxantrazole. A central composite experimental design was used to simultaneously evaluate a variety of formulation factors on a number of response variables, such as the percentage of oxantrazole entrapped in the MCM. In association with the study design, statistical optimization procedures indicated the factors that significantly influence MCM preparation and what levels of the factors are needed to produce optimum MCM. Entrapment of anticancer agents into biodegradable microspheres is difficult because of low aqueous drug solubility and porosity of the particles. The latter effect was circumvented by a chitosan cross-linking step that resulted in approximately 3% (w/w) oxantrazole entrapment in the MCM via the optimization procedures. The combined formulation and statistical optimization strategy provide a basis to develop other microparticulate systems and led to a dosage form that can be used for future in vivo investigations. PMID- 1614974 TI - Mechanisms to control drug release from pellets coated with a silicone elastomer aqueous dispersion. AB - The mass transport of two different compounds through polydimethylsiloxane (PDMS) silica films was investigated to demonstrate qualitatively how this coating system can alter the release of various compounds. Various ratios of PDMS elastomer and silica were used to coat monodisperse particle-sized pellets layered with an ionizable compound (tartrazine) and a nonionized compound (acetaminophen). The 2:1 PDMS-silica composition containing the polyethylene glycol (PEG) 8000 pore former allowed mainly pore transport through void spaces in the PDMS films. Both compounds rapidly diffused through the film as a result of the solubilization and subsequent removal of the PEG 8000 from the film matrix. As the PDMS-silica ratios in the films changed from a 1:1 to a 2:1 to a 4:1 (all without polyethylene glycol 8000) coating formulation, the differences in release rate between acetaminophen and tartrazine changed. The lower ratio of PDMS-silica allowed much faster tartrazine diffusion compared to acetaminophen. As the ratio increased from 1:1 to 2:1, the two compounds were released at similar rates. When the ratio reached 4:1, acetaminophen was released significantly faster than tartrazine. Explanations for these differences and the mechanisms controlling the drug release are discussed in the text. In some circumstances, osmolality and pH affected drug release from dosage forms coated with this polymer system. This study demonstrated that utilization of this polymer system offers a useful tool for the formulation scientist to modify release rates of ionic and nonionic drug substances. PMID- 1614975 TI - Effect of surfactant phase in perfluorocarbon emulsification efficiency. AB - The effect of preparation temperature on the emulsification efficiency of perfluoro-3-butyltetrahydrofuran (FC-75) was investigated. Polyoxyethylene (POE) oleyl ether surfactants were used as the emulsifier(s) in a range of HLB values of 7.5 to 9.5. The emulsions were prepared by paddle mixing as a method of low shear emulsification. After centrifugation of the resulting O/W emulsions, the volume of FC-75 which separated was utilized as a measure of the emulsification efficiency. In general, emulsions prepared at temperatures where the surfactant was in a lamellar-to-isotropic surfactant solution transition, L alpha----L3, displayed a better emulsification efficiency than those prepared with other surfactant phases. PMID- 1614976 TI - A novel method for determination of sterility of microcapsules and measurement of viability of encapsulated organisms. AB - A method of determining the viability of microencapsulated microorganisms (Bacillus Calmette Guerin) is reported. This method was also used to measure the effectiveness of aseptic production of microcapsules in maintaining the interior of the microcapsules free from contamination by microorganisms. This method is advantageous over conventional plating methodology, as plating can only determine external contamination of microcapsules and similar devices. It involves the detection of 14CO2, which is generated by the metabolism of 14C-labeled fatty acid in the growth medium by encapsulated microorganisms. The method depends on the semipermeable nature of the microcapsule walls, which allows passage of 14C palmitic acid and 14CO2. BCG organisms encapsulated within an alginate-polylysine alginate microcapsule (5-15 microns) (1) were shown to be viable, and no contaminating organism(s) was present. Methods suitable for the aseptic production and freeze drying of alginate-polylysine-alginate BCG microcapsules, which retain the viability of the organisms, are reported. PMID- 1614977 TI - Application of curdlan to controlled drug delivery. I. The preparation and evaluation of theophylline-containing curdlan tablets. AB - To study the use of curdlan, a natural beta-1,3-glucan, in drug delivery, in vitro release studies were carried out with curdlan tablets containing theophylline. Tablets were readily prepared by compressing three different curdlan and theophylline mixtures, namely, a physical mixture, spray-dried curdlan particles with theophylline powder, and spray-dried particles of curdlan/theophylline solution. Drug release from the tablets prepared from spray dried particles of curdlan/theophylline was lowest. The release rate was constant from 1 to 8 hr, and 59% cumulative release was obtained at 8 hr. Drug release from curdlan tablets was unaffected by pH or various ions; these curdlan tablets might also control drug release in vivo after oral administration. Application of Higuchi's equation indicated that drug release from curdlan tablets was diffusion controlled. The release profiles of the curdlan tablets were compared to those of a commercial theophylline sustained-release tablet. PMID- 1614978 TI - The disposition of a human relaxin (hRlx-2) in pregnant and nonpregnant rats. AB - The pharmacokinetics and tissue distribution of a human relaxin were investigated after intravenous (iv) bolus administration to pregnant or nonpregnant rats. Human gene-2 relaxin (hRlx-2) serum concentrations after iv bolus administration were described as the sum of three exponentials. The pharmacokinetics were comparable in pregnant and nonpregnant rats. The serum clearance (CL) was 7.4 10.2 ml/min/kg at doses of 46-93 micrograms/kg and was linear in this range. The half-lives were 1.1-2.0, 15.1-16.4, and 53.7-67.9 min, respectively. The volume of the central compartment (Vc) was 48-79 ml/kg and the volume of distribution at steady state (Vss) was 271-336 ml/kg. Increasing the dose to 463 micrograms/kg increased the dose-corrected area under the serum concentration-time curve and significantly decreased CL and Vss. The distribution of radioactivity in the tissues of pregnant rats was followed after iv bolus dosing with hRlx-2 internally labeled with 35S-cysteine. Comparison of the extent of organ uptake of radiolabel after 35S-hRlx-2 or 35S-cysteine administration suggested that the kidneys were the principal site of uptake; the liver was of secondary importance. In perfusion experiments utilizing livers isolated from pregnant or nonpregnant rats, 36-52% of the dose of hRlx-2 was cleared from the perfusate in 2 hr. These studies showed that the pharmacokinetics of hRlx-2 in rats appeared to be unaffected by pregnancy and suggested that the kidneys and liver both play a role in the elimination of hRlx-2. PMID- 1614979 TI - Sustained delivery of interleukin-2 from a poloxamer 407 gel matrix following intraperitoneal injection in mice. AB - Parenteral delivery of recombinant biologic response modifiers (BRMs) remains a challenge because of the brief intravascular half-life of most recombinant proteins and their associated rapid clearance from the circulation. Recombinant derived interleukin-2 (rIL-2) was formulated with Pluronic F-127, N.F. (poloxamer 407, N.F.) and the biological activity determined vs time at 4, 22, and 37 degrees C. As assessed by rIL-2-induced peripheral blood lymphocyte (PBL) uptake of [3H]thymidine, storage of rIL-2/poloxamer 407 (33% w/w) for 72 hr at 4 and 22 degrees C did not result in an overall negative slope of the [3H]thymidine vs time profiles. However, storage of an rIL-2/poloxamer formulation at 37 degrees C for 72 hr resulted in an approximate 15% reduction in the biological activity as assessed by [3H]thymidine incorporation. As assessed by bioassay ([3H]thymidine uptake), the cumulative percentage rIL-2 released in vitro at 22 degrees C after 8 hr from rIL-2/poloxamer 407 matrices containing either 30% (w/w) or 35% (w/w) poloxamer 407 was 81.8 +/- 1.7 and 82.1 +/- 4.7%, respectively. When ELISA was used to determine the amount of rIL-2 released vs time, the corresponding values for the cumulative percentage rIL-2 released were 82.6 +/- 10.1 and 40.9 +/- 8.8%. Cytotoxicity of rIL-2 stimulated PBLs cultured with poloxamer 407 (0.17%, w/w) toward malignant Daudi cells was significantly (P less than 0.05) enhanced compared to controls. Finally, mice injected with the rIL-2/poloxamer 407 formulation (1 x 10(5) U/inj. q.d. x 3 days) demonstrated a bioequivalent effect of rIL-2-induced natural killer (NK) cell activity in vitro toward malignant murine YAC-1 cells at one-half the standard exogenously administered dose of rIL 2 known to generate enhanced NK lytic activity in mice (1 x 10(5) U/inj. b.i.d. x 3 days). No untoward systemic side effects were observed for mice injected i.p. with polymer vehicle alone (30%, w/w) (0.15 ml q.d. x 3 days), pH 7 phosphate buffered saline (PBS) (0.15 ml q.d. x 3 days), rIL-2 formulated with poloxamer 407 (30%, w/w) (1 x 10(5) U/0.15 ml q.d. x 3 days and 0.5 x 10(5) U/0.15 ml q.d. x 3 days), or rIL-2 dissolved in PBS (1 x 10(5) U/0.15 ml b.i.d. x 3 days).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1614980 TI - The influence of peptide structure on transport across Caco-2 cells. II. Peptide bond modification which results in improved permeability. AB - In order to study the influence of hydrogen bonding in the amide backbone of a peptide on permeability across a cell membrane, a series of tetrapeptide analogues was prepared from D-phenylalanine. The amide nitrogens in the parent oligomer were sequentially methylated to give a series containing from one to four methyl groups. The transport of these peptides was examined across confluent monolayers of Caco-2 cells as a model of the intestinal mucosa. The results of these studies showed a substantial increase in transport with each methyl group added. Only slight difference in the octanol-water partition coefficient accompanied this alkylation, suggesting that the increase in permeability is not due to lipophilicity considerations. These observations are, however, consistent with a model in which hydrogen bonding in the backbone is a principal determinant of transport. Methylation is seen to reduce the overall hydrogen bond potential of the peptide and increases flux by this mechanism. These results suggest that alkylation of the amides in the peptide chain is an effective way to improve the passive absorption potential for this class of compounds. PMID- 1614981 TI - Prenatal diagnosis of alpha-1-antitrypsin deficiency by PCR of linked polymorphisms: a study of 17 cases. AB - We describe our experiences of prenatal diagnosis of alpha-1-antitrypsin deficiency using closely linked polymorphisms detected by Southern blotting and the polymerase chain reaction. Prenatal diagnosis was carried out for 17 pregnancies from 15 couples. PMID- 1614982 TI - Rapid prenatal diagnosis of trisomy 18 and triploidy in interphase nuclei of uncultured amniocytes by non-radioactive in situ hybridization. AB - Two biotinylated chromosome-specific DNA probes were used to quantify the number of chromosomes 18 and 1 in uncultured amniocytes. Thirty-three samples of uncultured amniocytes were hybridized with a chromosome 18-specific DNA probe. Uncultured cells from two of the 33 samples were also hybridized with a chromosome 1-specific probe. Thirty of the samples were disomic with respect to chromosome 18; two samples were trisomic with respect to chromosome 18, and one sample was trisomic with respect to chromosomes 1 and 18. The two cases of trisomy 18 and the single case of triploidy were identified on uncultured cells within 48-72 h after amniocentesis. They were found among five samples from pregnant women who had amniocentesis because of an ultrasonographically identified fetal malformation. A trisomic karyotype could be diagnosed with certainty in uncultured amniocytes because the majority of the responding nuclei exhibited three hybridization signals. In normal cells, the majority of nuclei exhibited two signals. In no cases was there discordance between the genotype as predicted by in situ hybridization and that determined by cytogenetic analysis. PMID- 1614983 TI - Evaluation of prenatal diagnosis by a registry of congenital anomalies. AB - Prenatal diagnosis performed by fetal karyotype and ultrasound scan is now a routine part of antenatal care in many countries. How many fetal anomalies are actually detected by these procedures? We have used our registry of congenital malformations to answer this question. In our region, prenatal diagnosis was performed in 23.1 per cent of fetuses with a chromosomal aberration and in 20.1 per cent of fetuses with non-chromosomal anomalies. Only 6.9 per cent of the pregnancies with fetuses with non-chromosomal anomalies were terminated. The sensitivity of prenatal diagnosis by ultrasonographic examination was much lower for isolated malformations (fetuses with only one anomaly) than for multiple malformed children, 15.3 and 48.3 per cent respectively, chromosomal anomalies excluded. PMID- 1614984 TI - Cardiotocographic and sonographic findings in two cases of antenatally diagnosed intrauterine fetal brain death. AB - Intrauterine fetal brain death is a rare cause of a fixed fetal heart rate pattern. Seven cases have been previously reported in the literature, but only two of them were diagnosed prenatally and all the newborns died soon after delivery. Two additional cases of antepartum diagnosis of intrauterine fetal brain death, managed expectantly, are reported. We had the unique opportunity to document progressive sonographic cerebral changes during the follow-up period, following the neurological event, while the fetus continued life and growth in utero. The cardiographic and sonographic findings suggesting intrauterine fetal brain death were a prolonged fixed fetal heart rate, even following a vibroacoustic and contraction stress test; an atonic fetus without breathing and body movement; and the appearance of hydramnios and the development of ventriculomegaly. PMID- 1614985 TI - Genetic amniocentesis at 7-14 weeks of gestation. AB - Genetic amniocentesis performed at 7-14 weeks of gestation was studied in a series of 138 patients of whom 50 wanted termination of pregnancy (less than or equal to 12 weeks). The material for analysis consisted of 132 samples due to two sampling failures and four samples being handled incorrectly. Forty-eight samples (36 per cent) were taken at 7-12 weeks of gestation, mainly transvaginally (36/48: 75 per cent). The success rate of culture and karyotyping increased with the duration of pregnancy, but was only satisfactory from week 11 onwards. The time until harvest was then 14-15 days. The transvaginal approach is easy to perform and was accepted by the women, but we experienced bacterial or fungal overgrowth in 17 per cent of these samples, whereas no infection occurred in the samples taken transabdominally (n = 96). We conclude that genetic amniocentesis is feasible from week 11, but further studies concerning side effects, especially focusing on the procedure-related abortion risk, should be carried out before early amniocentesis is routinely applied. PMID- 1614986 TI - Clues and pitfalls in the early prenatal diagnosis of 'late onset' infantile polycystic kidney. AB - Infantile polycystic kidney disease (IPKD) is an autosomal recessive inherited disorder, IPKD has been previously diagnosed by us as early as the 14th week of gestation. 'Late onset' (third trimester) IPKD has been previously described by several authors. We present here a case of intrauterine detection of 'late onset' IPKD, suggesting that elongated hyperechogenic kidneys (with normal transverse and anteroposterior diameters) should be considered as an early sign of 'late onset' presenting IPKD. PMID- 1614988 TI - Chang medium raises the chromatin instability of pericentromeric areas of chromosome 1 in amniotic fluid cells. PMID- 1614987 TI - Prenatal diagnosis of Fryns' syndrome. AB - We report on a new case of ultrasonographic prenatal diagnosis of Fryns' syndrome during the second pregnancy of a young woman whose first child died 90 min after birth and was diagnosed as having this autosomal recessive condition. The feasibility of diagnosis in utero and timing in the phenotypic expression of this multimalformation syndrome are discussed. PMID- 1614989 TI - Mosaic tetrasomy 12p: a new case. PMID- 1614990 TI - Correlates of maintenance of a low-fat diet among women in the Women's Health Trial. AB - BACKGROUND: The Women's Health Trial (WHT) was a feasibility study for a randomized controlled trial designed to test the hypothesis that a reduction in dietary fat reduces breast cancer incidence among women age 45 to 69. Between 1984 and 1988, 2,064 women participated in its two phases. METHODS: A follow-up study of 525 women who were randomized to receive the WHT dietary intervention program was conducted to assess maintenance of the diet 1 year on average after the trial ended. Among 448 participants, the mean percentage of energy from fat as measured by a food frequency questionnaire was 40.0% at baseline, 26.3% at the end of the trial, and 27.7% at follow-up. Based on 408 women with complete data, a recursive model was estimated, describing the influence of baseline characteristics of the women on attendance at intervention program sessions, adherence to the diet during the trial, and long-term maintenance of the diet after the trial ended. The effects of women's experiences during the trial on adherence and long-term maintenance were investigated as well. RESULTS: Attendance at the educational sessions was strongly related to adherence to the diet during the trial (P less than 0.001), and adherence was the most important predictor of long-term maintenance (P less than 0.001). The percentage of energy from dietary fat at baseline was an important correlate of both adherence (P less than 0.001) and long-term maintenance (P less than 0.001). College-educated women were more likely to adhere to the diet during the trial (P less than 0.001). Feelings of deprivation adversely affected long-term maintenance (P less than 0.01), primarily through their effect on adherence during the trial (P = 0.01). Costliness of the diet in time and money negatively influenced long-term maintenance (P less than 0.05). Development of a distaste for fat encouraged adherence (P = 0.06). CONCLUSIONS: The low-fat dietary pattern established during the WHT was maintained for as long as 20 months after the trial ended. A recursive model was useful in analyzing the process and correlates of long-term maintenance of dietary behavior change. Both predisposing variables and women's experiences while on a low-fat diet were associated with long-term maintenance. The results suggest that feelings of deprivation should be avoided, perhaps by use of low-fat substitutes, by those attempting to lower their dietary fat and that more research is needed on the development of a distaste for fat among individuals who adopt low-fat diets. PMID- 1614992 TI - Sun exposure and sunscreen use following a community skin cancer screening. AB - BACKGROUND: In May 1988, a community skin cancer screening was held, and of the 251 individuals who attended, 214 (85%) completed a follow-up questionnaire. The objective of this study was to examine the associations among attitudes, knowledge, and behavior in those who had attended the screening. RESULTS: Analysis showed that females were twice as likely to have false positive screening diagnoses as males (odds ratio 2.2; P = 0.06). Attitudes toward tanning were not correlated with knowledge about the harmful effects of excess sun exposure (rp = -0.02; P = 0.67) or with behaviors such as reported sun exposure (for positive attitude versus "poor" attitude, linear trend P less than 0.11) and sunscreen use (linear trend P = 0.70). Behavior, defined as reported sunscreen use, was highly correlated with knowledge, both of the harmful effects of the sun and of the definition of SPF (linear trend P less than 0.001). Sunscreen use was also associated with the younger age group (those less than 59, P less than 0.05), female sex (P less than 0.001), higher education (P less than 0.05), and perceived risk for melanoma (P less than 0.05). CONCLUSIONS: We conclude that more targeted education in the domain of knowledge would benefit males and those over the age of 59. PMID- 1614991 TI - Body mass and acute myocardial infarction. GISSI-EFRIM Investigators. AB - BACKGROUND: The relation between body mass index and acute myocardial infarction was analyzed using data from a multicentric case-control study conducted in Italy between September 1988 and June 1989 within the framework of the GISSI-2 trial. METHODS: Subjects were 916 patients with acute myocardial infarction and no history of cardiovascular disease and 1,106 controls hospitalized for acute conditions not related to known or suspected risk factors for ischaemic heart disease. RESULTS: Relative to the lowest quintile of the Quetelet Index (weight/height2) the estimated risks for subsequent quintiles were 1.2 (95% confidence intervals, (CI): 0.9 to 1.6), 1.7 (95% CI: 1.2 to 2.2), 1.8 (95% CI: 1.4 to 2.4), and 2.2 (95% CI: 1.7 to 3.0) when adjustment was made for age, sex, education, and smoking habits by means of logistic regression. The association was consistent across strata of sex, education, and smoking status, but not age. The estimated risk for subjects in the fifth quintile of the Quetelet Index relative to those in the first was 4.1 under 55 years of age, but only 1.7 between 55 and 64 years and 1.5 above age 65. CONCLUSION: The relation between body mass and myocardial infarction was explained, at least in part, by higher serum cholesterol levels and the prevalence of diabetes and hypertension among fatter subjects. This does not, however, totally eclipse a possible causal relation between body mass and risk of myocardial infarction, since these conditions are a consequence, rather than a confounder, of overweight. PMID- 1614993 TI - Characteristics of heavy smokers. AB - BACKGROUND: Heavy smokers (those who smoke greater than or equal to 25 or more cigarettes a day) are a subgroup who place themselves and others at risk for harmful health consequences and also are those least likely to achieve cessation. Despite this, heavy smokers are not well described as a segment of the smoking population. METHODS: We used representative population data on 1,048 smokers to examine differences between heavy and lighter smokers (less than or equal to 24 cigarettes per day). RESULTS: Heavy smokers constituted 26.7% of all cigarette smokers. Compared with lighter smokers, heavy smokers were significantly more likely to be male, to be age 30 years or older, to smoke their first cigarette of the day within 30 min of waking, to perceive quitting as very difficult, to have little confidence in their ability to quit, to be less likely to report variation in their rate of smoking between work and leisure days, and to be less likely to be employed. CONCLUSIONS: Public health strategies which may particularly assist heavy smokers include stronger restrictions on smoking in public places, nicotine replacement therapies, and the use of segmentation research to more carefully target campaign messages to influence quit attempts and confidence. PMID- 1614995 TI - Green tea composition, consumption, and polyphenol chemistry. AB - Tea is grown in about 30 countries but is consumed worldwide, although at greatly varying levels. It is the most widely consumed beverage aside from water with a per capita worldwide consumption of approximately 0.12 liter per year. Tea is manufactured in three basic forms. Green tea is prepared in such a way as to preclude the oxidation of green leaf polyphenols. During black tea production oxidation is promoted so that most of these substances are oxidized. Oolong tea is a partially oxidized product. Of the approximately 2.5 million metric tons of dried tea manufactured, only 20% is green tea and less than 2% is oolong tea. Green tea is consumed primarily in China, Japan, and a few countries in North Africa and the Middle East. Fresh tea leaf is unusually rich in the flavanol group of polyphenols known as catechins which may constitute up to 30% of the dry leaf weight. Other polyphenols include flavanols and their glycosides, and depsides such as chlorogenic acid, coumarylquinic acid, and one unique to tea, theogallin (3-galloylquinic acid). Caffeine is present at an average level of 3% along with very small amounts of the other common methylxanthines, theobromine and theophylline. The amino acid theanine (5-N-ethylglutamine) is also unique to tea. Tea accumulates aluminum and manganese. In addition to the normal complement of plant cell enzymes, tea leaf contains an active polyphenol oxidase which catalyzes the aerobic oxidation of the catechins when the leaf cell structure is disrupted during black tea manufacture. The various quinones produced by the enzymatic oxidations undergo condensation reactions which result in a series of compounds, including bisflavanols, theaflavins, epitheaflavic acids, and thearubigens, which impart the characteristic taste and color properties of black tea. Most of these compounds readily form complexes with caffeine. There is no tannic acid in tea. Thearubigens constitute the largest mass of the extractable matter in black tea but their composition is not well known. Proanthocyanidins make up part of the complex. Tea peroxidase may be involved in their generation. The catechin quinones also initiate the formation of many of the hundreds of volatile compounds found in the black tea aroma fraction. Green tea composition is very similar to that of the fresh leaf except for a few enzymatically catalyzed changes which occur extremely rapidly following plucking. New volatile substances are produced during the drying stage. Oolong tea is intermediate in composition between green and black teas. PMID- 1614994 TI - Availability of cigarettes to underage youth in three communities. AB - BACKGROUND: Underage youth report that they primarily obtain cigarettes from commercial sources. Thus policies that effectively prevent purchase by minors could have an effect on the prevalence of young people's cigarette use. METHODS: In this study, 12- to 15-year-old male and female confederates attempted to purchase cigarettes from all cigarette outlets in three communities. RESULTS: A success rate of 53% over the counter and 79% from vending machines was achieved. These results show that minors can purchase cigarettes in all types of businesses, even those characterized as "adult" locations. Boys in this study had more difficulty than girls in purchasing cigarettes over the counter, and younger individuals had more difficulty than 15-year-olds. However, these differences were not found in vending machine sales. Similarly, over-the-counter sales of cigarettes were significantly reduced following a state-wide increase in the penalty for tobacco sales to minors, but vending machine sales were not affected. CONCLUSIONS: These results support stringent and universal controls over the sale of cigarettes as an essential part of any tobacco use prevention strategy. PMID- 1614996 TI - Tea components: antimutagenic and anticarcinogenic effects. AB - BACKGROUND: Tea from the Camellia sinensis species of the Theaceae family is one of the most ancient and, next to water, the most widely consumed beverage in the world. Since tea contains several polyphenols and since several other naturally occurring dietary polyphenols have shown antimutagenic effects in bacteria and anticarcinogenic effects in animal bioassay systems, we studied whether polyphenols extracted from Chinese green tea (GTP) also possess antimutagenic and anticarcinogenic effects. RESULTS: GTP and its constituent epicatechin derivatives were found to interact with hepatic cytochrome P450 (P450) and inhibited the P450-dependent mixed-function oxidase enzymes in skin and liver. GTP and its epicatechin derivatives exhibited antimutagenic effects in several test systems. GTP showed substantial anti-skin-tumor-initiating and anti-skin tumor-promoting activities when assessed in murine skin tumorigenesis bioassay systems. In these model systems polyaromatic hydrocarbons, benzo[a]pyrene (BP), 3 methyl-cholanthrene, 7,12-dimethylbenz[a]anthracene, and (+)-7 beta,8 alpha dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (an ultimate carcinogenic metabolite of BP) were used as model skin carcinogens. The feeding of GTP in drinking water to SKH-1 hairless mice also afforded significant protection against ultraviolet-B-radiation-induced skin photocarcinogenesis. CONCLUSIONS: These data suggest that tea components possess antimutagenic and anticarcinogenic effects, and that they could protect humans against the risk of cancer by environmental agents. PMID- 1614998 TI - Suppression of genotoxicity of carcinogens by (-)-epigallocatechin gallate. AB - Epidemiological evidence shows that green tea may be a factor in lowering cancer risk. We have investigated the possibility that (-)-epigallocatechin gallate (EGCG), a major polyphenol in green tea, might be an antimutagenic substance. In the Ames Salmonella test, EGCG suppressed the direct-acting mutagenicity of 3 hydroxyamino-1-methyl-5H-pyrido-[4,3-b]indole (Trp-P-2(NHOH)) and 2-hydroxyamino 6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1(NHOH)), the activated forms of food-derived carcinogens 3-amino-1-methyl-5H-pyrido[4,3-b]indole and 2-amino-6 methyldipyrido[1,2-a:3',2'-d]imidazole. EGCG was also effective in reducing the mutagenicity of Trp-P-2(NHOH) in mouse FM3A cells in culture. Furthermore, EGCG demonstrated a suppressive effect in the in vivo Drosophila mutation assays, i.e., the wing spot test, and the DNA repair test, on several carcinogens. EGCG was also effective in inhibiting DNA single-strand breaks in vitro caused by Glu P-1(NHOH). We conclude that the mechanism of inhibition may not have resulted from direct interaction between EGCG and the mutagens, but rather from indirect interception of mutagen action by EGCG. PMID- 1614999 TI - Teas and tea components as inhibitors of carcinogen formation in model systems and man. AB - BACKGROUND: Epidemiological evidence points to a cancer protective role of green yellow-orange vegetables and fruits. The involvement of teas as a protective factor in carcinogenesis has not received the attention it seems to merit. To gain relevant information, attempts were made to stimulate in vitro those conditions to which human groups are actually exposed. METHODS: The inhibitory effects of infusions of Chinese, Japanese, and Ceylonese teas were examined by adding them to a nitrosation mixture consisting of 0.8 mg sodium nitrite and 340 mg equivalent of a widely consumed salt-preserved fish (Pak Wik) and estimating the frequency of mutants in TA 1535 strain of Salmonella typhimurium. RESULTS: The tea samples exhibited a strong inhibitory effect at concentrations that are actually ingested by man. A comparable inhibition was obtained by several tea phenolics. A second series of experiments dealt with the formation of nitrosoproline (NPRO) which can be strongly inhibited in vitro by the tea infusions and tea phenolics. The effects of the tea infusions and caffeic acid on the endogeneous formation of NPRO in man were examined by having volunteers ingest 300 mg sodium nitrate and 30 min later 300 mg proline, collecting urine samples over a 24-hr period, and estimating the excreted NPRO. The tested teas, at doses regularly consumed, again exerted a strong inhibitory effect on endogeneous NPRO formation in humans. Comparable inhibitory effects were obtained by ingesting caffeic acid, chlorogenic acid, or ferulic acid with the nitrosation mixture. CONCLUSIONS: These results indicate that the simultaneous intake of teas with food products that are being nitrosated within the stomach of human subjects should exert a protective, beneficial effect. PMID- 1615000 TI - The effects of Chinese tea on the occurrence of esophageal tumors induced by N nitrosomethylbenzylamine in rats. AB - BACKGROUND: Based on previous studies on the blocking effect of Chinese tea in the formation of N-nitroso compounds in rats and humans, experiments were carried out to study the effects of Chinese tea on the occurrence of esophageal tumors induced by N-nitrosomethylbenzylamine (NMBzA) in rats. METHODS: In the first experiment, rats were given two precursors of NMBzA, i.e., sodium nitrite and methyl benzylamine, p.o. After 12 weeks, the incidence of esophageal tumors was 95%. However, in the five groups of tea (green tea, jasmine tea, black tea, and oolong tea)-treated rats, the incidences were only 5-19%. In the second experiment, preformed NMBzA was administered to rats. RESULTS: The incidences of esophageal tumors in the five tea-treated groups were 42-67%, while in the positive control group, without tea, the incidence was 90%. Histopathological examination showed the same protective effects of tea treatment. In a separate study, a significant reduction of O6-methylguanine (MeG) and the ratio of O6-MeG to N7-MeG was observed in rats treated with oolong tea and jasmine tea. PMID- 1614997 TI - Inhibitory effect of green tea on tumorigenesis by chemicals and ultraviolet light. AB - Topical application of a green tea polyphenol fraction inhibited 12-O tetradecanoyl-phorbol-13-acetate-induced tumor promotion in CD-1 mice previously initiated with 7,12-dimethylbenz[a]anthracene (DMBA). Oral administration of a green tea infusion as the sole source of liquid sustenance to SKH-1 mice inhibited ultraviolet B light (UVB)-induced sunburn lesions, UVB-induced initiation of skin tumors, UVB-induced formation of skin tumors in mice previously initiated with DMBA, and nitrosodiethylamine-induced forestomach and lung tumors in A/J mice. In addition to inhibiting UVB-induced formation of skin tumors in DMBA-initiated mice, oral administration of green tea markedly decreased tumor size. PMID- 1615001 TI - [Does the sinu-bronchial syndrome exist?]. PMID- 1615002 TI - [In vitro studies of cellular immunity in chronic bronchitis with and without corticosteroid medication]. AB - In 29 patients with chronic bronchitis, 17 of whom were receiving systemic prednisolone, parameters of cellular and humoral immunity from the blood were evaluated and compared with a control group. Serum concentrations of immunoglobulins IgG, A and M, IgG subclasses, lymphocyte subsets and lymphocyte response to mitogenes (PHA, ConA, PWM), antibodies (anti-CD3) and tetanus antigen were determined. Whereas T cell subsets did not show any difference between all groups, the relative proportion of B lymphocytes was lower in the patient group without corticosteroids. Both patient groups showed a decreased lymphocyte response. As expected, serum IgG was lower in the steroid group, which could not be explained by additional cellular findings. Our data indicate that patients suffering from chronic bronchitis may show signs of a decreased cellular immunity. PMID- 1615003 TI - [Comparison of two different methods for measuring interoception of obstructions in asthma patients]. AB - For measuring the interoception of airway resistance, bronchial obstructions are often simulated by flow-resistive loads applied externally (i.e. outside the body) into the respiratory flow. However, it is open to doubt whether interoception characteristics obtained in this manner are really related to the clinical pattern of complaints of asthmatic patients. Possibly such externally applied resistance simulates merely an aspect of the physics of apnoea but not a clinical and hence also psychological aspect of the same. To estimate the significance of these aspects for the perception of obstructions, this ability was measured in 25 asthmatic patients first by means of external added loads; this test was then repeated by noting the subjective assessment of bronchial obstructions caused during a routine histamine provocation test. Both interoception parameters correlated only slightly (rxy = 0.31) which is discussed as a pointer to the assumption that, among other parameters, psychological factors may considerably modify the perception of flow resistivity. No correlations were seen between the characteristic interoception value obtained by means of mesh resistivities and the different variables of the clinical pattern of symptoms. On the other hand, the interoception parameter measured on the basis of bronchial obstructions revealed significant connections with several clinical variables: the greatly increased incidence of respiratory distress at night or during certain external conditions, coping medication, physical exercise and style. It is concluded that only such parameters of perception of obstructions are clinically relevant for patients suffering from asthma, which consider not only the somaticophysical but also the psychic component of asthmatic respiratory distress. PMID- 1615004 TI - [Revascularization of heterotopic isotransplants of the rat trachea using an omentum flap]. AB - Donor airway ischemia remains a significant problem following lung transplantation. An acceleration of local bronchial revascularization would be advantageous for bronchial healing. In the present study, the quantitative effects of omentopexy on tracheal revascularization and epithelial regeneration were investigated in a heterotopic rat tracheal isograft model. Tracheal segments were harvested from donor rats and heterotopically implanted into the omentum of syngeneic recipient rats. Tracheal segments were wrapped for 2 days (group 2), 7 days (group 3) or 14 days (group 4). Tracheal segments in group 1 were harvested and not re-implanted. Following sacrifice of the animals after 2, 7 or 14 days, the vascularity of the tracheas and the tracheal epithelial morphology were assessed histologically using morphometric image analysis. The vascularity of tracheal segments was significantly higher in group 1 (native tracheas) compared to all other groups. Vascularity in group 4 segments (omental wrap for 14 days) was significantly greater than in group 3 segments (omental wrap for 7 days). Tracheal epithelial morphology was characterized by non-confluent single epithelial cells at day 2, a confluent multilayered nonciliated epithelium after 7 days of omental wrap and a morphologically normal epithelium after 14 days of omental wrap. Our new heterotopic rat tracheal isograft model allows histologic assessment and quantification of local revascularization and epithelial regeneration of tracheal segments by omentopexy. PMID- 1615005 TI - [Emissions of airborne substances from stalls of domestic animals]. AB - There is concern on recent reports indicating an increase of respiratory affections in humans in areas with high livestock production. A survey is presented on airborne emissions from livestock buildings. About 136 gaseous compounds are analysed in animal house air of which 22 are quantified, only. The most environment-related compounds are ammonia and methane. It is assumed that German animal husbandry emits more than 350,000 t ammonia per year. The content of airborne microorganisms in livestock buildings is between some 100 and several 1000 per liter. The greatest part, more than 80%, are Staphylococcae and Streptococcae. Fungi, moulds and yeasts can form more than 1%, and coli-like bacteria about 0.5% of the total amount. Moulds like Penicillium, Aspergillus, Cladosporium and Alternaria were identified which are known to have allergic properties. The average concentrations of dust in animal barns vary between 0.5 and 20 mg/m3. The dust contains high amounts of protein and carries endotoxins which both have an allergic potential. Preliminary results show that the germ content of the surrounding air in areas with high animal densities seems to be distinctly higher than in non-livestock regions. PMID- 1615006 TI - [Esophago-thoracic fistula after pneumonectomy and long-term main bronchus stump fistula]. AB - A woman patient admitted for treatment, who had reached the age of 65 years, had a previous history of an open pulmonary tuberculosis in 1946 that had been treated at that time by means of collapsotherapy and phrenico-exeresis. Pleuropneumonectomy was performed in 1976 because of a residual cavity of a thoracic empyema. Since 1978 the patient suffered from a fistula of the bronchus treated by postural therapy without achieving a cure. In 1989 a fistula formed between oesophagus and pneumonectomy cavity. Clinically this was associated with an increasing reduction of performance and a suddenly ineffective postural drainage, resulting in triphasic and eventually fatal aspiration. Histology revealed a suppurative inflammation in the fistular channel and a slight superficial Candida colonisation of the pneumonectomy cavity, of the fistular channel and of adjacent mucous glands of the oesophagus. Formation of the fistula was probably due to a small traction diverticulum followed by perforation because of obstructed oesophageal passage due to scarified distortions. PMID- 1615007 TI - Vitamin A status: relationship to immunity and the antibody response. PMID- 1615008 TI - Comparison of copper binding components in dog serum with those in other species. AB - The copper content of dog serum and its distribution to copper binding proteins was compared with that of rat and mouse. Total serum Cu concentrations of dogs and mice were one third those of the rat. Plasma ceruloplasmin, determined by azide-inhibitable oxidase activity with two substrates, was 8-fold less in the dog and 9- to 20-fold less in the mouse than in the rat, and, in both dogs and mice, there was 70-75% less ceruloplasmin Cu, determined by atomic absorption after gel filtration. In the dog, the largest proportion of total and exchangeable serum Cu was with the transcuprein fraction. Only one third as much Cu was with albumin in the dog (and mouse) versus the rat, and this was released much more readily through dialysis. In dogs and mice, the exchangeable (nonceruloplasmin) serum copper pool was half the size of that in rats and humans. Especially in the mouse (but also in rats and dogs), a small proportion of the exchangeable pool appeared bound to ferroxidase II. We conclude that the dog may rely more on transcuprein and low molecular weight complexes and less on albumin and ceruloplasmin for transport of copper to cells. PMID- 1615009 TI - Enhanced growth restriction of Legionella pneumophila in endotoxin-treated macrophages. AB - Macrophages from A/J mice are permissive for growth of Legionella pneumophila, an intracellular opportunistic pathogen that grows preferentially in macrophages. Macrophages from other mouse strains are highly resistant to growth of Legionella. In the present study, it was found that macrophages from A/J mice are readily activated by pretreatment with lipopolysaccharide (LPS), so that the cells do not permit Legionella to replicate in vitro, as occurs when untreated macrophages from A/J mice are cultured with these organisms for 48 hr. The augmentation of Legionella growth inhibition by LPS-activated macrophages from nonpermissive BDF1 mice also occurred. After in vitro infection, there was a 1000 fold increase in the number of Legionella in A/J macrophages and approximately a 10-fold increase in BDF1 macrophages, but LPS treatment of macrophages from either strain resulted in marked growth restrictions. This suppression was both dose dependent as well as dependent upon the time of addition of the LPS to the macrophages. Furthermore, the lipid A component of LPS was found to be as effective as the intact LPS in activating macrophages to inhibit the intracellular growth of Legionella. Further studies concerning the mechanisms involved are clearly warranted and in progress. PMID- 1615010 TI - Effect of triacontanol on numbers and functions of cells involved in inflammatory responses. AB - A preparation of a triacontanol-containing compound was studied for its effect on cells involved in the inflammatory response. C57BL/6 mice were injected intraperitoneally with various concentrations of this compound and investigated for total body weight, wet weight of thymus tissue, number of thymus cells and splenocytes, interleukin 1 production of spleen monocytes, and response of splenocytes to the T cell mitogen, phytohemagglutinin. Mice treated with the triacontanol preparation exhibited decreased total body weight, 24% reduction in thymus weights, 39% decrease in the number of thymus cells, and 21% depression in total splenocytes. Splenic monocytes of these animals produced a significantly reduced amount of interleukin 1 and splenocytes had a significantly depressed response to phytohemagglutinin. It is concluded that triacontanol has an inhibitory effect on at least some of the cells responsible for inflammation. PMID- 1615011 TI - Impaired febrile response with age: role of thermogenesis in brown adipose tissue. AB - We demonstrated previously that in Escherichia coli-infected rats, the heat necessary for the febrile response is a result of thermogenesis in brown adipose tissue (BAT). To investigate whether senescent rats have an impaired febrile response to infection and whether such an impairment is a result of attenuated sympathetically activated thermogenesis in BAT, we assessed body temperature and the increase in mitochondrial guanosine 5'-diphosphate (GDP) binding sites in interscapular BAT in response to E. coli administration in young and senescent male F-344 rats. There was a significant delay of 2 hr in the onset of fever in the older animals. In addition, in senescent rats, the peak fever (1.0 +/- 0.1 delta degrees C vs 2.2 +/- 0.1) and the cumulative fever (383 +/- 43 delta degrees C.min vs 775 +/- 69) were significantly less than in the young rats (P less than 0.005). Baseline levels of GDP binding were the same in young and old rats. In young rats, during the rising phase of the fever, E. coli infection resulted in a 50% increase in the density of GDP binding sites in BAT mitochondria. In contrast, there was no increase in GDP binding in the older rats following infection. The failure to increase GDP binding may be a result of a reduced ability to unmask reserve GDP binding sites. Alternatively, there may be fewer total GDP binding sites (masked and unmasked) in senescent rats and these sites may already be unmasked. Collectively, these data suggest that the impaired febrile response with age is due to reduced thermogenesis in BAT. PMID- 1615012 TI - Viscoelastic influence on wall and baroreceptors of rabbit carotid sinus. AB - This study examined multifiber baroreceptor nerve activity (BNA) as a function of carotid sinus wall distension in 19 rabbits. Analysis estimated mechanical or viscoelastic properties of the sinus wall and their influence on BNA. In six sinuses, properties were altered by treatment with the enzyme protease to remove the endothelium and with nifedipine to passively relax smooth muscle. Properties were estimated from dynamic and steady state wall response to a 45 mm Hg step increase and decrease in intrasinus pressure (ISP) of 20 min. Control wall response had fast and slow (creep) portions with a viscosity increase from 1,370 N(s)/m to 17,864 N(s)/m during step-up in ISP. Wall elasticity averaged 77 N/m; which estimated the relationship of force and change in steady state response. Control BNA response also had fast and slow (resetting) portions. A BNA and wall response relationship (BNA/m) was defined as transduction-gain (T-G) with proportional and dynamic components. In the subgroup, wall creep and baroreceptor resetting were abolished by protease treatment, suggesting an endothelial mediator which influenced sinus smooth muscle. Histology data indicated enzyme damage was limited to tunica intima tissues, and nifedipine did not block Ca2+ channels on neural structures. By comparison of responses before and after treatments the proportional component of T-G was equated to an elastic influence (1/E), with E = 7.5 x 10(-6) m/BNA, while the dynamic component was equated to a viscous influence (1/V), with V = 1.53 x 10(-4) m(s)/BNA. A simple but fundamental relationship for baroreceptor-tissue linkages was estimated by BNA/m = 1/(Vs + E), a first-order transfer function. PMID- 1615013 TI - Blood flow measurements by the reference sample method with microsphere injection in to the aorta: an accurate and easy approach. AB - The validity of hemodynamic measurements by the reference sample method with microspheres injection into the aorta, via a carotid artery catheter, was evaluated in rats and compared with the results obtained after left ventricle injection. In the aorta injection group, a good mix of microspheres was observed in 83% of the animals. Moreover, a symmetrical distribution of microspheres was observed in 10 out of 12 rats (83%). An excellent correlation between right and left kidney-testes blood flows was observed (r = 0.93 and 0.96, respectively; P less than 0.01). Mean arterial pressure was not modified during microspheres injection into the aorta. Cardiac output (104 +/- 26 vs 101 +/- 23 ml/min, NS) and portal blood flow (14.2 +/- 3.3 vs 13.5 +/- 2.2 ml/min, NS) were similar after aorta and left ventricle injections series, respectively. Our results indicate that the injection of microspheres into the aorta is an adequate and easy approach to systemic and splanchnic hemodynamic measurements. This approach could be a good alternative to left ventricle injection of microspheres in experimental studies in rats. PMID- 1615014 TI - Renal actions of endothelin during mannitol and saline expansion. AB - We evaluated the effects of volume expansion with saline (0.5 ml kg-1 min-1, n = 13) and with 10% mannitol in saline (0.5 ml kg-1 min-1, n = 13) on the cardiorenal actions of endothelin-1 (ET) in rats anesthetized with sodium pentobarbital. We also evaluated to what extent the calcium channel antagonist, verapamil (0.02 mg kg-1 min-1), altered the cardiorenal actions of endothelin in volume-expanded rats (n = 10 with saline and n = 10 with mannitol). In five rats from each group, renal blood flow was measured with an electromagnetic flow probe. Sixty minutes after surgery, control clearances were collected, ET (110 ng kg-1 min-1) was then infused for 30 min, and recovery clearances were collected for 60 min. ET caused a similar increase in mean arterial blood pressure and decrease in renal blood flow and the glomerular filtration rate in the saline and mannitol groups. Verapamil significantly attenuated but did not abolish the ET induced increase in mean arterial blood pressure in both saline- and mannitol treated rats. By contrast, the calcium channel antagonist had no effect on the ET induced decrease in either the glomerular filtration rate or renal blood flow in saline-treated rats, but significantly attenuated these responses to ET in mannitol-expanded animals. These data demonstrate that (i) the systemic and renal responses to ET are not affected by expansion with saline or mannitol and (ii) the renal vasoconstriction prompted by endothelin is not affected by verapamil in saline-expanded rats, but is attenuated by the Ca2+ channel antagonist during expansion with mannitol. These data suggest that during volume expansion with mannitol, but not with saline, the ET-induced renal vasoconstriction occurs primarily at intrarenal resistance sites that are dependent upon extracellular Ca2+. PMID- 1615015 TI - Circadian rhythm of ornithine decarboxylase activity in small intestine of fasted rats. AB - The aim of this study was to determine whether the circadian changes in ornithine decarboxylase (ODC) activity of different segments of the small intestine were governed by factors other than food intake. First, the effects of fasting on mucosal ODC activity were examined. The results indicate that mucosal ODC activity in 24 hr and 48 hr fasted rats decreased significantly compared with ad libitum-fed rats. Second, the circadian rhythm of mucosal ODC activity was characterized by measuring mucosal ODC activity in fasted rats at four time points (09:00, 15:00, 21:00, and 03:00 hr; light period: 06:00-18:00 hr). The results from this study indicate that there is a detectable baseline ODC activity in different segments of fasting intestine. In duodenum, mucosal ODC activity was highest at 15:00 hr (light period), a time at which the rat was normally not eating. In jejunum and ileum, mucosal ODC activity increased between 21:00 and 03:00 hr (dark period). The observation that small intestine exhibits a distinct circadian rhythm of ODC activity in fasted rats suggests that not only food but also intrinsic factors can modulate physiologic oscillations in mucosal ODC activity. PMID- 1615016 TI - Human beta-interferon incubated with muscle homogenate is protected by albumin but not by proteinase inhibitors. AB - The scarce bioavailability of beta-interferon (IFN-beta) after intramuscular administration is probably due either to the binding of IFN-beta to interstitial matrix, or to lymphatic absorption and/or to local breakdown by lysosomal proteinases from muscle. In this work, we first showed that after intramuscular injection, the apparent bioavailability of natural human IFN-beta is about 10% of that of recombinant IFN-alpha 2 and then we evaluated the effects of proteinase inhibitors and albumin on IFN-beta incubated at 37 degrees C with muscle homogenate. IFN biological activity decreased spontaneously by about 20% after incubation for 6 hr at 37 degrees C in Hanks' solution, but it was almost completely lost after incubation with muscle homogenate. Proteinase inhibitors (alpha 1-antitrypsin, alpha 2-macroglobulin, aprotinin, soybean trypsin inhibitor, leupeptin, EP-459, and EP-475) failed to block the inactivation of IFN beta by muscle proteinases, whereas albumin exerted a partial but consistent protection. PMID- 1615017 TI - Effects of H-2 and vitamin A on micrognathia in congenic mice. AB - Pregnant mice congenic with C57BL/10 (B10.A, B10.BR, B10.D2, B10.A(2R), B10.A(5R), B10.A(15R), B10.A(1R), B10.A(18R), and B10.OL) were fed Purina Mouse Chow or the same diet plus 200 IU of vitamin A daily. The pregnant dams were sacrificed on the eighteenth day of gestation, and the fetuses were sexed and examined for defects in mandibular development. On average, micrognathia occurred five times more frequently in female (1.5%) than male (0.3%) fetuses. The addition of vitamin A to the diet affected only females, reducing the frequency of this defect to that observed in males from dams fed the control diet. Micrognathia was strongly associated with micro- or anophthalmia, but not with defects of the palate. C57BL/10 fetuses had the highest frequency of micrognathia (3.2%) and B10.D2 and B10.A(5R) fetuses had the lowest (0.1%). The results suggest that a locus distal to C4 and perhaps proximal to Qa-1 may exert a moderate influence on mandibular development and a second locus proximal to E beta may have a weak effect. PMID- 1615018 TI - Stromal cells derived from spleen or bone marrow support the proliferation of rat natural killer cells in long-term culture. AB - Rat nylon wool nonadherent bone marrow cells were propagated for up to 75 days in co-culture with stromal cells derived from either spleen or bone marrow. Interleukin (IL) 1 enhanced the ability of spleen stroma to support the long-term culture of natural killer (NK) cells, ostensibly by inducing these support cells to synthesize other cytokines. Flow cytometry studies indicated that the nylon wool separation procedure enriched the concentrations of mature NK cells from 7.9% to 38.1% for splenocytes and from 3.8% to 19.5% for bone marrow cells. Analyses of the adherent zones of suspended nylon screen NK cell cultures revealed substantial numbers of large granular lymphocytes that expressed NK 323+/MOM/3F12/F2- phenotypes. The presence of both mature and immature cells of the NK lineage in this matrix was inferred by the presence of both IL-2 receptor (IL-2R) positive and IL-2R negative, and OX-8+ and OX-8- NK 323+ cells over the greater than 4-month experimental period. Suspended nylon screen cultures displayed a greater potential for producing cytolytic cells than either co cultures of bone marrow nonadherent cells on stroma monolayers or suspension cultures. The large granular lymphocytes produced in suspended nylon screen cultures could be transformed into active killers of YAC-1 targets by IL-2. In contrast to bone marrow nonadherent cells, more splenic nylon-wool-passed cells displayed a mature NK phenotype, but their proliferative potential and ability to be transformed into cytolytic cells by IL-2 decreased rapidly in culture. In the suspended nylon screen culture system, NK cells migrate from the underlying stroma in stages as they mature, retain their cytolytic potential, and manifest a capacity for self-renewal. Cultured cells were routinely dissociated into single cell suspensions via enzyme treatment and were reinoculated onto "fresh" nylon screen/stromal cell templates after passage through nylon wool columns. These co cultures continued to generate cytolytic cells in numbers greater than those of the initial inoculum. PMID- 1615019 TI - [The pharmacology of superoxide dismutase]. PMID- 1615020 TI - [PAF-antagonists with phospholipid structure. 4. Alkylcarbamoylphospholipids with heteroarene and heterocyclase head groups and variation of the P-N-distance; synthesis, characterization and structure-activity relationship]. AB - A series of 11 PAF-analogues, structurally modified in position 1 (alkylcarbamoyloxy), position 2 (n-propyl), and position 3 (polar head group) were synthesized, and the inhibitory potencies on human blood platelets in vitro was evaluated. Investigations of structure-activity relationships revealed, that the PAF antagonist activity is strongly influenced by the chain length of the alkylcarbamoyl residue and the structure of the polar head group. Derivatives with pentadecyl and octadecylcarbamoyl structure emerged effective inhibitors. The best activity was observed by dimethylaminopyridinium, analogues with a P-N distance of 3 or 4 methylene groups and pentadecyl or octadecylcarbamoyl structure (IC50 = 1.0-1.6 mumol/l). PMID- 1615021 TI - Nonsteroidal antiinflammatory agents. Part 21: optically active stereoisomers of p-trifluoromethylphenyl- and p-thioanisyl-biphenylyl- hydroxypropionic acids. AB - The synthesis, diastereomeric separation, assignment to erythro- and threo configuration by 1HNMR, and optical resolution of 3-(p-trifluoromethyl-phenyl)- and (p-thioanisyl)-2-biphenylyl-3-hydroxypropionic acids are described. The enantiomers were submitted to a preliminary assay to determine antiinflammatory activity. PMID- 1615022 TI - Synthesis of some N-substituted indole derivatives and their biological activities. AB - Acylation of 2,3-diphenyl-5-methoxy-indole using ethyl chloroformate or chloroacetyl chloride in dimethylformamide and sodium hydride yielded the N substituted derivatives 1 and 2, respectively. While Friedel-Crafts acylation using chloroacetyl chloride afforded di-4,6-chloroacetyl derivative 3, the reaction of the N-chloroacetyl derivative 2 with amines, hydrazines, urea, semicarbazide hydrochloride, thiophenol, benzimidazole-2-thiol, thiosemicarbazide, 2-mercaptoethanol and thioglycolic acid was studied. Several of the compounds were tested for their effect on arterial blood pressure, antiinflammatory and ulcerogenic activities. PMID- 1615023 TI - [Synthesis and antimicrobial activity of chlorobenzyl benzylidene imidazolidinedione derivatives and substituted thiazolidinediones]. AB - The synthesis of five chlorobenzyl benzylidene imidazolidinediones and four fluorobenzyl benzylidene thiazolidinediones is described. In order to investigate their antimicrobial activity they are evaluated against microorganism such as Candida albicans, Neurospora crassa, Staphylococcus aureus, Mycobacterium smegmatis and Escherichia coli. PMID- 1615024 TI - [Potential cardiotonics. 13. Crystal structure, charge distribution and molecular electrostatic potential of 3-cyano-2-(3-diethyl-aminopropylamino)-5-(4 pyridinyl)pyridine (AWD 122-60)]. AB - The crystal and molecular structure of the potential cardiotonic agent AWD 122-60 have been determined by X-ray structure analysis. Based on the molecular structure charge distribution and molecular electrostatic potential were evaluated. The results are discussed in comparison with those of other cardiotonic 3,4'-bipyridines. PMID- 1615025 TI - [The use of bead cellulose for controlled drug liberation. 5. Kinetics of liberation of bonded drugs from bead cellulose and bead cellulose derivatives]. AB - Examination of in vitro liberation of prazosin hydrochloride and benzocaine from formulations of matrix type with bead cellulose and bead cellulose derivatives shows deviations from first order kinetics owing to competition of several processes: dissociation of ionic bonds or cleavage of covalent bonds between drugs and bead cellulose, pore diffusion, dissolution of the drugs and swelling of cellulose matrix. Suitable combinations of different bonded portions of the drug on bead celluloses let these complexes seem to be successful in the use for controlled and retarded liberation of drugs. PMID- 1615026 TI - [Rheology and extensiometry of ophthalmic preparations with a vegetable oil base]. AB - The physical characteristics of ophthalmic preparations based on vegetable oils destined for hot climates was studied in part by determining their rheological properties and also by measuring their extensibility. The results obtained showed that the thixotropy of the formulations studied was a favorable property which would permit their uniform application to the surface of the eye. PMID- 1615027 TI - Liposomes as a potential drug carrier for citicoline (CDP-choline) and the effect of formulation conditions on encapsulation efficiency. AB - In this paper we report the investigation of the potential of liposomes as drug carrier for citicoline (1; CDP-choline). The aim of our work is to improve the pharmacokinetic and pharmacodynamic parameters of the drug to facilitate the overcoming of the blood-brain barrier. The thermotropic behaviour of hydrated dispersions of various phospholipids and their mixtures containing 1 have been investigated by differential scanning calorimetry (DSC) to have a clear view of the interaction between the drug and the liposome phospholipids. By the values of transition peak temperature (Tm) and transition enthalpy (delta H) we note a strong interaction between 1 and the polar heads of L-alpha dipalmitoylphosphatidic acid (DPPA) and L-alpha-dipalmitoylphosphatidylserine (DPPS), whereas there is not any considerable interaction between the drug and L alpha-dipalmitoylphosphatidylcholine (DPPC) or L-alpha dimyristoylphosphatidylcholine (DMPC); in any case no interaction occurs between 1 and the hydrophobic part of the phospholipid. So we conclude that all the drug is fitted into the aqueous spaces. The results of the encapsulation efficiency experiments demonstrate how the encapsulation capacity increase with using charged phospholipids, reaching the top with DPPA. Moreover, it was noted that the presence of Cholesterol (Chol) enhances the encapsulation capacity (EC) and drug content (DC) values of DPPC, a neutral phospholipid. The size of the liposomes was determined by light scattering (LS). PMID- 1615028 TI - Study of the gastrointestinal diffusion system (GDS): influence of acacia gum on mechanical and chemical properties in free cellulose acetate films. AB - In this work a study of free cellulose acetate films was carried out in the presence and absence of acacia gum at high concentrations (50 and 75%). The mechanical toughness and the aspect were influenced by operatory conditions and by the relative air humidity. The increase of relative humidity from about 0% to 75% decreased the mechanical toughness and the color film changed from a clear to opaque white. The presence of acacia gum decreased the mechanical toughness and the water vapour transmission rate and increased the film water solubility. PMID- 1615029 TI - Pharmacokinetics of isometronidazole. Basic model and estimation of the kinetic parameters from experimental data. AB - For the optimal timing of application of radiosensitizers in a course of radiotherapy it is important to know the sensitizer concentration at the time of irradiation. We have studied the pharmacokinetics of the hypoxic cell sensitizer isometronidazole in man and mouse and analyzed the data on the basis of an open two-compartment model after extravasal application. The parameter estimation is performed directly to avoid estimation biasing and data points from blood and tissue compartments are approximated simultaneously. The values obtained differ significantly from the estimations calculated by other authors for the same data. PMID- 1615030 TI - [Antitussive action of extracts and polysaccharides of marsh mallow (Althea officinalis L., var. robusta)]. AB - The complex extract and the polysaccharide isolated from the roots of marsh mallow were tested for antitussive activity in unanaesthetized cats of both sexes. Cough was elicited by mechanical stimulation of laryngopharyngeal and tracheobronchial mucous area of the respiratory system with a Nylon fibre (diameter 0.35 mm). Cough was evaluated on the basis of the changes in lateral tracheal pressure. The polysaccharide and the complex extract were administered p.o. in a dose of 50 and 100 mg/kg b.w., respectively. The efficiency of the mentioned compounds was compared with the cough-suppressing effect of drugs belonging to the non-narcotic antitussics. The results of the experiments showed that administration of the polysaccharide led to a statistically significant decrease of the number of cough efforts both from laryngopharyngeal and tracheobronchial areas of the the respiratory system. The polysaccharide in a dose of 50 mg/kg b.w. was as effective in inhibition of the cough reflex as Sirupus Althaeae in a dose of 1000 mg/kg b.w. and more effective than prenoxdiazine in a dose of 30 mg/kg b.w. However, the cough-suppressing effect of the polysaccharide was lower than that of dropropizine. The extract was less effective than the polysaccharide. PMID- 1615031 TI - [Tyrosine splitting aminopeptidases on cultivated anterior hypophyseal and vascular endothelial cells]. AB - Activities of aminopeptidases for a tyrosine peptide hydrolysis were characterized with Tyrosyl-7-amino-4-methyl-coumarin as substrate on in vitro cultivated anterior pituitary cells, respectively, on aortic endothelial cells. Furthermore the corresponding activities were measured in different fractions of the cells. The activities of the enzymes in soluble fractions of the cell homogenates are comparable with aminopeptidases of cytosolic compartments of other tissue samples. On the other hand remarkable differences exist between Km- and IC50-values of the membrane preparations of both cell types. Furthermore, the substrate degradation on intact cells by provable membrane bound ectoenzymes is identically for both cell types and this degradation is insensitive for amastatin. Our results are discussed with special respect for the importance of the degradation of biological active peptides with N-terminal tyrosine by aminopeptidases on their physiological targets. PMID- 1615032 TI - HPLC quantification of a tricomponent psychiatric formulation containing chlorpromazine, trifluoperazine and trihexyphenidyl. PMID- 1615033 TI - In vitro and in situ absorption of ethamsylate. Part 1: A simple spectrophotometric method for in situ intestinal absorption using phenol red as volume marker. PMID- 1615034 TI - The timing control of geminate and single stop consonants in Japanese: a challenge for nonnative speakers. AB - The stop closure durations and voice onset time of geminate and single voiceless stops in Japanese were examined with two groups of subjects: native Japanese and fluent Americans. The two groups were found to have different manners of timing control of these segments. The results indicated that the 10 native speakers distinguished between the geminate and single stops by controlling the closure durations in the mean ratio of 2.8:1.0, while the 4 fluent Americans pronounced the same tokens in diverse and random manners. The timing control of geminate and single stop consonants is a challenge for nonnative speakers who may either miss the contrast, or may pronounce geminate and single stops with the ratio of approximately 2.0:1.0. PMID- 1615035 TI - Speaking fundamental frequency patterns of Japanese women. AB - The purpose of this research was to obtain information on the speaking fundamental frequency (SFF) mean levels, variability and patterns of Japanese females and contrast them with those of Caucasian speakers of American English. To this end, 56 young women--32 Japanese and 24 Americans--read standard passages in either or both the Japanese and English languages. It was found that the Japanese exhibited higher fundamental frequencies than did the Americans for all speaking conditions, and this contrast was statistically significant. Additionally--and unlike the American speakers--most Japanese women exhibited bimodal SFF distribution patterns. It is judged that the observed differences in level and distribution result primarily from differences in the structure of the two languages. PMID- 1615036 TI - Stops in the world's languages. AB - This account of the great variety of stops in the world's languages shows that, apart from their place of articulation, these sounds can be described principally in terms of the activities that occur at three phases: onset, closure, and release. Other potentially contrastive features discussed include length, and the use of the glottalic airstream mechanism (other airstream mechanisms are not considered here). Phonologically only two phases--closure and release--are exploited; independent distinctions of features such as phonation type or articulatory manner cannot be found in the onset phase. We examine the combinatorial possibilities of the features that are used and discuss implications for phonological feature systems. PMID- 1615037 TI - Spatial learning ability of rats undernourished during early postnatal life. AB - Experiments to determine whether undernutrition during early life results in deficits in spatial learning behavior has produced conflicting results. It was hypothesized that this may be due to the differing degrees of undernutrition used in the various studies, and/or to the timing of the testing procedures with respect to the period of food deprivation. These possibilities were tested by undernourishing rats between birth and 30 days of age to two different levels (i.e., level-1 and level-2). The degree of undernutrition was greater at level-2 than level-1. Behavioral testing of these rats and well-fed controls was carried out in the Morris water maze when they were between either 35 and 65 or 170 and 200 days of age. Statistical analyses of the escape latency data from these experiments revealed that rats tested almost immediately after the period of undernutrition have alterations in their spatial learning behavior compared with controls. However, even a short period of nutritional rehabilitation removed any differences between control and previously undernourished groups, irrespective of the level of undernutrition. PMID- 1615038 TI - Parametric manipulations and fixed-interval self-stimulation. AB - Three experiments investigated hypothalamic self-stimulation under a fixed interval (FI) reinforcement schedule. An FI 20-s schedule was chosen to reduce stimulation density in order to minimize the influence of priming effects or stimulation aftereffects that can affect responding under other schedules of reinforcement. The first experiment showed that the influence of train duration is greatest at levels up to 1 s and thereafter level off over a wide range of train durations (1-32 s). The second experiment showed that altering frequency, current, or pulse width produced almost identical changes in FI responding. These findings show that the neutral network subserving hypothalamic self-stimulation simply integrates the amount of charge over time. It is relatively insensitive to the combination of stimulation parameters that make up a given waveform. In the third experiment, the chronaxies from the strength-duration curves indicate the neural substrate supporting self-stimulation has a great current-integrating capacity. Together, these experiments show that varying the amount of brain stimulation produce large and consistent changes in a number of FI response measures. These measures effectively describe different attributes of FI performance and include response rate, the postreinforcement pause, interresponse times of short duration and the temporal distribution of responses within the interval. PMID- 1615039 TI - Autonomic nervous system response patterns correlate with mental imagery. AB - New findings related to autonomic nervous system (ANS) functions may reveal some brain functions, since they can be observed by real time analysis. ANS parameters (skin potential and resistance, skin temperature and blood flow, instantaneous heart rate) and instantaneous respiratory frequency are quantified by original techniques and indices. Results show that ANS responses correlate with mental imagery. Imagery contents influence autonomic responses, thus making it comparable to real activity. Therefore, by using two shooting events as models, the almost identical nature of the ANS response is evidenced during real shooting and in mental concentration before shooting. Next, shooting activity imagery can be distinguished from neutral imagery but is comparable to the activity itself as far as ANS responses are concerned. PMID- 1615040 TI - Smooth muscle sensitization and neuromuscular depression induced by chronic administration of antimalarial drugs. AB - The functional effects on chick smooth and skeletal muscle of chronic administration of 60 mg kg-1 chloroquine or quinacrine given as daily intraperitoneal injections for 70 days have been investigated. Noradrenaline and potassium chloride (KCl) contracted the normal expansor secundariorum muscle, a smooth muscle from the wing of chicks wholly innervated by noradrenergic nerves. The muscle was unresponsive to acetylcholine and histamine. Chronic administration of chloroquine or quinacrine induced supersensitivity of expansor muscles to KCl and the muscles were contracted by acetylcholine and histamine. These actions were more pronounced in quinacrine-treated chicks and could be due to direct smooth muscle sensitization that may result in postjunctional changes. The oesophagus is a smooth muscle that is predominantly under parasympathetic control. The oesophagus from chronically-treated chicks was more sensitive to acetylcholine and KCl than the control muscles. This sensitization was more marked for chloroquine than quinacrine. Chronic administration of chloroquine and quinacrine depressed skeletal muscle contractions evoked by acetylcholine and potassium chloride. These findings indicate that chronic chloroquine and quinacrine administration sensitise smooth muscle to agonist drugs but depress neuromuscular transmission. PMID- 1615041 TI - Interstrain aggression in hypertensive and/or hyperactive rats: SHR, WKY, WKHA, WKHT. AB - Four inbred rat strains, all derived from Wistar-Kyoto (WKY) rats, express hypertension and hyperactivity in all combinations: SHRs have both traits, WKYs have neither, WKHAs are hyperactive/normotensive, and WKHTs are hypertensive/normoactive. Rats of the four strains were tested for aggression, at one time only, by pairing subjects of same sex, same age, but different strain, in a novel arena, i.e., on neutral ground, for three consecutive, 5-min observation periods. Total aggression scores were highest in females, highest in the first 5-min period, and lower at 7-9 months than at younger ages. Allogrooming was more frequently observed than other types of aggression, such as attacks, mounts, aggressive postures, and blocks. Allogrooming scores were significantly elevated in the hypertensive strains, especially WKHT, and very low in the hyperactive strains, especially WKHA. The other forms of aggression were significantly higher in females with hyperactivity. It was concluded that interstrain aggression, as seen in SHRs and WKYs, is differentially expressed by two new strains genetically derived from them. Furthermore, no one strain among these four expresses all components of the behavioral responses seen in this form of aggression. PMID- 1615042 TI - Genotype, uterine position, and testosterone sensitivity in older female mice. AB - CF-1 and CK (C57BL/6J x AKr) female mice that developed in utero between two males (2M), adjacent to one male (1M), or between two females (0M) were tested for their sensitivity to the aggression-promoting property of testosterone (T) beginning at 9 months of age. Comparisons between the strains showed that a higher proportion of CF-1 females fought in response to T and that the period of hormone exposure required to induce aggression also was shorter in this strain. Within each of the genotypes, there were no systematic differences in responsiveness to T related to contiguity to males during fetal development. While the results provide further evidence for genotype as a major influence on neural sensitivity to androgen, they do not support uterine position of females relative to males as a source of phenotypic variation in responsiveness. PMID- 1615043 TI - The performance of WKY rats on three tests of emotional behavior. AB - The behavior of Wistar, Fischer-344, and WKY male rats was observed on three tests of emotional behavior. These included the defensive-withdrawal test, the elevated plus maze, and the conditioned defensive-burying test. Rats were subsequently exposed to the water-restraint ulcerogenic procedure. Fischer-344 rats were more active in the defensive-withdrawal tests, but other behavioral measures in this test did not discriminate between the three strains. Scores reflecting anxiety in the elevated plus maze were lowest for Fischer-344 rats and highest for WKY rats, but the anxiety scores of WKY rats did not differ significantly from Wistar rats. The behavior of WKY rats was significantly different from the other two strains in the conditioned defensive burying test. While the degree of anxiety is measured by burying behavior, elicited by the novelty of prod shock, immobility was the prevalent response of WKY rats. WKY rats also revealed significantly higher ulcer severity scores when exposed to water-restraint stress after each behavioral test procedure. We propose that WKY rats are hyperresponsive to stress and that novelty stress elicits depression like behavior, which is the prevalent behavioral stress response in WKY rats. PMID- 1615044 TI - Cholecystokinin antagonist and lipid intake as a function of caloric density and familiarity. AB - The effect of treatment with the cholecystokinin antagonist L364,718 on intake of different dilutions of corn oil emulsion was tested under two levels of familiarity with the oil emulsion. No increase in intake was observed. To see if the CCK antagonist was effective under our conditions, exogenous CCK was administered under the same conditions. A complete suppression of the large reduction produced by CCK on intake was found. PMID- 1615045 TI - Amiloride reduces intensity responses of human fungiform papillae. AB - Microdrop stimulation of human fungiform papillae was used to confirm that the drug amiloride reportedly reduces the taste response to NaCl and sucrose. Amiloride caused magnitude reductions of saltiness in most subjects and of sweetness for some but not all subjects. More of the subjects showed a reduction in response to NaCl than a reduction to sucrose and there were individual differences in the strength of the reduction of magnitude. PMID- 1615046 TI - Human psychophysical studies of saltiness suppression by amiloride. AB - Two studies were performed to assess the effects of amiloride on the saltiness of NaCl. In the first study, four highly trained subjects were asked to report the first appearance of saltiness as NaCl microdrops were rapidly applied to an increasing number of fungiform papillae along the front, dorsal surface of the tongue. For two subjects, amiloride, a sodium channel blocker, caused a large and significant increase in the number of papillae needed to report a salty taste. The other two subjects were unaffected, as measured by this procedure. In the second study, four different subjects were trained in the same procedure as in the previous study. For testing, however, they were stimulated on a fixed number of papillae, which was two times the number self-selected during training as sufficient for perception of saltiness with NaCl, and sourness with citric acid. They reported the quality of the experience as salty, sour, or neither, with and without amiloride treatment of the papillae set. Two of the four subjects had a loss of saltiness of NaCl, but not sourness of citric acid, when the papillae set was treated with amiloride. PMID- 1615047 TI - Rats can discriminate between the urine odors of genetically identical mice maintained on different diets. AB - Male Long-Evans hooded rats were tested in a habituation-dishabituation procedure for their ability to discriminate between the urine odors of male C57BL/6J mice maintained on two different diets. There were discriminable differences between the urinary odors of two individual mice maintained on different diets. The rats did not dishabituate when presented with urine odors from two individuals on the same diet or two odor samples from the same individual. These results indicate that individual urinary odors of genetically identical mice are influenced by diet. We discuss the hypothesis that diet may act together with genetic differences, commensal bacteria, and hormonal changes to convey olfactory information used for individual recognition. PMID- 1615048 TI - Photoperiod and gonadal hormones influence odor preferences of the male meadow vole, Microtus pennsylvanicus. AB - Male meadow voles housed in a long photoperiod (14 h light/day, LP) preferred female to male odors, whereas males maintained in a short photoperiod (10 h light/day, SP) did not display preferences for odors of either sex. These odor preference patterns matched those of free-living males during spring and autumn, respectively. The preference of LP male voles for female over male odors was eliminated by gonadectomy and reinstated by treatment with testosterone. In SP males, although gonadectomy did not affect odor choices, a preference for female odors was induced by testosterone treatment. Treatment with estradiol did not alter odor preferences of LP or SP males. In conjunction with previous result, the present findings suggest that hormonal responsiveness of neural substrates that control odor preferences are sexually dimorphic and may reflect sex differences in reproductive strategies. PMID- 1615049 TI - Circadian patterns of drinking and eating in pygmy goats. AB - The eating and drinking patterns of pygmy goats fed ad lib and kept on a 12 h light/12 h dark cycle were recorded and analyzed. Eighty-four percent of drafts (drinking bouts) were associated with meals (feeding bouts). Only 42% of meals were associated with drafts. In the light phase meals associated with drafts were significantly larger than meals not associated with drafts, suggesting that meal size is increased by water intake around meals. Cumulative food intake was positively correlated with cumulative water intake, but the correlation was weaker during the dark phase than during the light phase. The results demonstrate that water intake in ruminants is associated with food intake, but the link between water and food intake seems to be more pronounced during the light phase than during the dark phase. PMID- 1615050 TI - Effects of chronic dietary choline on temporal discrimination of BN and WAG rats. AB - Using rats of the inbred BN and WAG strain, we tested the hypothesis that chronic dietary choline supplementation would especially affect the timing behavior of BN rats because of their lower cholinergic activity and their poor performance in aversively motivated learning and memory tasks. An apparent effect of chronic choline supplementation (2.5 mg choline chloride per ml water) on DRL-8" responding was not confirmed in a second experiment when the choline concentration was doubled. WAG rats treated chronically with choline showed a poorer temporal discrimination performance on a DRL-16" schedule than untreated WAG rats. In contrast, choline supplementation never had an effect on the performance of BN rats. The results of the DRL-16" experiment provide partial support for a hypothesis proposed by Church and Meck that the remembered time of reinforcement is inversely related to the functional activity of brain cholinergic activity: acetylcholine precursor treatment increases memory storage speed, which results in an overestimation of the time elapsed. An alternative explanation, which takes into account the aberrant EEG activities of WAG rats, is also discussed. PMID- 1615052 TI - Comparison of preference thresholds for NaCl solution in rats of the Sprague Dawley and Long-Evans strains. AB - Rats of the Sprague-Dawley and Long-Evans strains were compared with respect to their preference threshold and preference maximum concentrations for NaCl solution in a two-bottle choice paradigm. The preference threshold for NaCl in rats of the Sprague-Dawley strain occurred when the concentration of NaCl presented was 0.030 M. The preference maximum concentration was 0.10 M. In the case of rats of the Long-Evans strain, a preference threshold concentration was not clearly manifested although the preference maximum concentration was also 0.10 M. Thus, the previously reported lack of an appetite for isotonic NaCl solution in rats of the Long-Evans strain compared to those of the Sprague-Dawley strain is most likely related to the failure of rats of the former strain to discriminate between water and NaCl solution until the concentration of NaCl exceeds 0.15 M. However, at this concentration, both strains rejected NaCl solution in favor of water. In contrast to the results with NaCl solution, rats of the Long-Evans strain appear to have a greater appetite for 5% glucose solution than do those of the Sprague-Dawley strain. Whether this is related to a reduced preference threshold concentration for glucose remains to be tested. PMID- 1615051 TI - Learned preference for the limiting amino acid in rats fed a threonine-deficient diet. AB - Preference for an odor associated with protein is only seen in protein-deprived rats. We hypothesized that rats depleted of the amino acid threonine (THR) would prefer a flavored solution paired with a THR replete diet. Rats were given a flavored drink paired with THR-deficient (DEV) diet followed by a second flavor paired with a corrected (COR) diet. In choice testing, the animals clearly selected the COR-paired flavor, while control rats preferred the other flavor. This did not, however, differentiate between aversion to the DEV-paired flavor and learned preference for the COR-paired flavor. In subsequent tests, an unpaired flavor was given rather than the DEV-paired flavor. The COR-paired flavor was included in the test as before. In the second and third trials, using either DEV or a less profoundly deficient diet, animals depleted of THR selected the COR-paired flavor to a greater extent than control rats. We conclude that animals deficient in the essential amino acid, THR, show a learned preference for the flavor paired with repletion. PMID- 1615053 TI - Influence of anterior subdiaphragmatic vagotomy and TPN on rat feeding behavior. AB - Total parenteral nutrition (TPN) inhibits food intake and feeding behavior. Whether caloric sensory function of the liver contributes to this food intake and feeding behavior regulation via vagal-afferent innervation was tested after performing anterior hepatic vagotomy or sham operation in rats infused with a TPN solution providing 100% of daily energy needs, given continuously for 4 days. Food intake, meal number, size, duration, meal and intermeal sniffs, and eating activity were measured using an automated computerized rat eater meter (ACREM). TPN infusion resulted in a significant decrease of food intake and feeding indexes in both groups. The vagotomized rats showed a significantly higher food consumption, achieved by greater meal frequency, larger meal size, and longer meal duration. Thus, vagotomized rats consumed more than their controls by eating larger meals more often and of longer duration. Data suggest that anterior hepatic vagotomy interrupts hepatic caloric sensory feedback loop, diminishing inhibitory vagal effects on food intake with TPN, leading to an overall increase in food intake. PMID- 1615054 TI - Lesions of the medial amygdala produce severe impairment of copulatory behavior in sexually inexperienced male rats. AB - The effects of amygdaloid lesions on masculine copulatory behavior were examined in male rats. Sexually inexperienced male rats were castrated and subjected to bilateral lesions in one of the following areas: the medial amygdala, the cortical amygdala, or the basolateral amygdala. Three weeks later, all rats received implantation of silastic capsules containing testosterone. Then, four observations of copulatory behavior were carried out every 5 days following the implantation of testosterone. Rats with medial amygdala lesions showed a severe deficit of copulatory behavior, whereas rats with basolateral amygdala lesions showed no change in the performance of copulation. As for rats with cortical amygdala lesions, although their copulatory behavior was impaired, the effect was confined to a deficit in intromission and ejaculation responses. These findings suggest that the medial amygdala plays a critical role in regulating masculine sexual behavior in the rat. PMID- 1615055 TI - Habituation and dishabituation of human salivary response. AB - Habituation may be relevant for understanding how sensory stimuli influence factors related to ingestive behavior. In the first of three experiments in humans we showed that salivation and hedonic ratings to lemon or lime juice habituated within 10 presentations, and dishabituation of the salivation and hedonic ratings to the original juice were observed after a new juice was presented. Experiment 2 replicated the habituation and decrease in hedonics to lemon juice, and showed both dishabituation and a relative increase in hedonics when chocolate taste, rather than another juice, served as the dishabituating stimulus. In a third experiment we showed a video game, a nontaste stimulus, could serve as a distractor to prevent the development of habituation, as well as a dishabituator after habituation had occurred. PMID- 1615056 TI - Effects of 2-deoxy-D-glucose on food intake of rats are affected by diet composition. AB - The effect of various doses of 2-deoxy-D-glucose (2-DG) on food intake in rats fed either a medium fat diet with a moderate carbohydrate content (MF-rats) or a carbohydrate-free high fat diet (HF-rats) was tested. Injections were given intraperitoneally either in the middle of the bright phase or 1 h after onset of the dark phase. During the light phase 2-DG induced a transient hyperphagia in both HF- and MF-rats, but the hyperphagia was somewhat less pronounced in HF rats. During the dark phase 2-DG produced a hyperphagia in the MF-rats and a long term hypophagia in the HF-rats. Since 2-DG elicited feeding in HF-rats during the light phase, the feeding response to 2-DG not only reflects hunger for carbohydrate as previously suggested but also seems to produce hunger for energy. PMID- 1615057 TI - Intrauterine positions and testosterone levels of adult male gerbils are correlated. AB - Those male Mongolian gerbils (Meriones unguiculatus) that developed in intrauterine positions between two male fetuses had significantly higher levels of serum testosterone, as adults, than did those adult male gerbils that developed in intrauterine positions between two female fetuses. The endogenous testosterone levels of adult male gerbils were significantly positively correlated with both the sizes of their ventral scent glands and their frequencies of scent marking. We found no evidence of pulsatile release of testosterone in adult male gerbils. PMID- 1615058 TI - Plasma catecholamines and social behavior in male vervet monkeys (Cercopithecus aethiops sabaeus). AB - Many investigations in humans indicate that epinephrine, norepinephrine and their ratio may correlate with such traits as social competence, academic achievement, and aggression. However, the socioeconomic, dietary, and environmental confounds accompanying most human studies complicate their interpretation. Social status, aggression, and other social behaviors can be reliably assessed in nonhuman primates under conditions controlling for crucial environmental factors. If interpretation of human studies is correct, dominant and subordinate male vervet monkeys should exhibit distinctive patterns of catecholamine secretion. To test this possibility, seventeen adult male monkeys living in six stable social groups were observed for 6 months. Based on their success in agonistic events, subjects were categorized as dominant or subordinate. Alpha scores were calculated from empirically derived factors to provide a noncategorical measure of dominant behavioral style. Plasma epinephrine and norepinephrine samples obtained from anesthetized subjects did not differ between dominant and subordinate males. Alpha scores, however, distinguished high from low norepinephrine/epinephrine ratio groups. These findings are consistent with studies in humans linking high epinephrine, low norepinephrine, and social competence. PMID- 1615059 TI - Senescence-accelerated mouse (SAM): age-related reduced anxiety-like behavior in the SAM-P/8 strain. AB - Age-related behavioral changes in the passive avoidance, food neophobia, elevated plus-maze, and water-lick conflict tests were studied using substrains of senescence-accelerated mouse (SAM-P/8 and SAM-R/1) at 2 to 20 months of age. SAM P/8 mice exhibited a significant impairment of acquisition of passive avoidance compared with SAM-R/1 mice when they were trained repeatedly, and the acquired response in SAM-P/8 mice rapidly diminished in contrast to good retention in SAM R/1 mice. SAM-P/8 mice showed an age-related decrease in the latency to eat novel food after a 24-h food deprivation as compared with SAM-R/1 mice at 2 to 12 months of age, despite no significant difference in latency to eat familiar food between the two strains. In the elevated plus-maze test, SAM-P/8 mice had apparent increases in the number of entries into open arms and time spent on open arms in comparison to SAM-R/1 mice at 4 through 12 months of age; this difference became obvious with aging, implying age-associated reduced anxiety in the SAM-P/8 strain. In addition, SAM-P/8 mice exhibited a significant increase in punished water drinking compared to SAM-R/1 mice in the water-lick conflict test, although unpunished water intake in SAM-P/8 mice did not differ from that in the SAM-R/1 control. Aged SAM-R/1 mice, 20 months old, exhibited low anxiety-like behavior in the food neophobia and elevated plus-maze tests such as was seen in SAM-P/8 mice, when compared with young (4-month-old) SAM-R/1 mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615060 TI - Maternal influences on body temperature in the infant primate. AB - The following study investigated the diurnal variation in body temperature of the young monkey infant and assessed the role that the mother plays in the development of the temperature rhythm. Using an implantable biotelemetry system, core body temperature and motoric activity were evaluated in maternally-reared and hand-reared rhesus monkey infants across the first several months of life. Our results indicated that the nocturnal temperatures of hand-reared infants are lower than those of mother-reared infants at one month of age, and that there are persistent differences in the orientation and shape of the diurnal temperature rhythm. The initial thermal challenge and the prolonged rhythm shift may have implications for the normal development of several physiological systems in the hand-reared infant monkey. PMID- 1615061 TI - Dietary self-selection vs. complete diet: body weight gain and meal pattern in rats. AB - Food intake and body weight gain of male adult Wistar rats were examined in two groups of animals. One group (n = 14) was allowed to select its diet from separate sources of protein (casein, 3.1 kcal/g), fat (lard and sunflower oil, 7.9 kcal/g) and carbohydrate (CHO, starch and sucrose, 3.3 kcal/g). Another group (n = 10) received a nutritionally complete diet (3.3 kcal/g). After 2 weeks of adaptation to the diets, body weights and meal patterns were recorded for at least 4 days. The total caloric intake was nearly identical for the two groups of rats. Rats given dietary choice gained less weight over 4 days than rats fed chow and showed reduced feed efficiency. During the 24-h period, self-selecting rats consumed 20.8% of calories as proteins, 21% as fats and 58.2% as CHO. Self selecting rats ate significantly less calories during the day than did rats given chow. The chow diet consisting of 17.3% calories as protein, 7.6% as fat and 75.1% as CHO. When comparing the self-selecting group nutrient intakes to those of chow-fed group it was observed that 24-h protein calorie intakes were identical in both groups. Fat intake was significantly higher and CHO reduced as compared to chow-fed rats. During the day, CHO intake was higher in self selecting rats, and fat intake was not significantly reduced. During the night, protein and fat intakes were significantly higher in self-selecting rats, while CHO intake was significantly decreased, particularly in the last periods of the night.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615062 TI - A staphylococcal multidrug resistance gene product is a member of a new protein family. AB - The complete nucleotide sequence (321 bp) of smr (staphylococcal multidrug resistance), a gene coding for efflux-mediated multidrug resistance of Staphylococcus aureus, was determined by using two different plasmids as DNA templates. The smr gene product (identical to products of ebr and qacC/D genes) was shown to be homologous to a new family of small membrane proteins found in Escherichia coli, Pseudomonas aeruginosa, Agrobacterium tumefaciens, and Proteus vulgaris. The smr gene was subcloned and expressed in S. aureus and E. coli and its ability to confer the multidrug resistant phenotype was demonstrated for two different lipophilic cation classes: phosphonium derivatives and quarternary amines. Expression of smr gene leads to the efflux of tetraphenylphosphonium and to a net decrease in the uptake of lipophilic cations. The deduced polypeptide sequence (107 amino acid residues, 11,665 kDa) has 46% hydrophobic residues (Phe, Ile, Leu, and Val) and 20% hydroxylic residues (Ser and Thr). Four transmembrane segments are predicted for smr gene product. Of the charged amino acid residues, only Glu 13 is located in a transmembrane segment. This Glu 13 is conserved in all members of the family of small membrane proteins. We propose a mechanism whereby exchange of protons at the Glu 13 is a key in the efflux of the lipophilic cation. This mechanism includes the idea that protons are transported to the Glu 13 via an appropriate chain of hydroxylic residues in the transmembrane segments of Smr. PMID- 1615063 TI - Cloning and DNA sequence of the Mycobacterium fortuitum var fortuitum plasmid pAL5000. AB - The complete nucleotide sequence of the Mycobacterium fortuitum var fortuitum plasmid pAL5000 has been determined. Computer analysis of this 4821-bp plasmid for protein coding regions, based on mycobacterial codon usage preferences, reveals the presence of two putative protein coding regions immediately downstream from typical mycobacterial promoter and ribosome binding sites. Both open reading frames, ORF1 and ORF2, produced proteins with the predicted respective sizes previously shown in minicell expression experiments [A. Labidi et al. (1985) FEMS Microbiol. Lett. 30, 221-225]. ORF1 encodes a putative 20-kDa basic protein with characteristics of a DNA binding protein involved in plasmid DNA replication. ORF2 encodes a 67-kDa protein with an amino-terminal sequence suggestive of a transported protein and a possible transmembrane anchor near its carboxyl-terminal. The current sequence and its analysis are more consistent with the minicell expression experiments than the previously published sequence of the pAL5000 plasmid [J. Rauzier et al. (1988) Gene 71, 315-321]. PMID- 1615064 TI - Heterologous gene expression in Bacteroides fragilis. AB - Bacteroides fragilis and other gastrointestinal tract Bacteroides are unusual gram-negative eubacteria in that genes from other gram-negative eubacteria are not expressed when introduced into these organisms. To analyze gene expression in Bacteroides, expression vector and promoter probe (detection) vector systems were developed. The essential feature of the expression vector was the incorporation of a Bacteroides insertion sequence element, IS4351, which possesses promoter activity directed outward from its ends. Genes inserted into the multiple cloning site downstream from an IS4351 DNA fragment were readily expressed in B. fragilis. The chloramphenicol acetyltransferase (cat) structural gene from Tn9 was tested and conferred chloramphenicol resistance on B. fragilis. Both chloramphenicol resistance and CAT activity were shown to be dependent on the IS4351 promoters. Similar results were obtained with the Escherichia coli beta glucuronidase gene (uidA) but activity was just 30% of the levels seen with cat. Two tetracycline resistance determinants, tetM from Streptococcus agalactiae and tetC from E. coli, also were examined. tetC did not result in detectable tetracycline resistance but the gram-positive tetM gene conferred high-level resistance to tetracycline and minocycline in Bacteroides hosts. Based on the cat results, promoter probe vectors containing the promoterless cat gene were constructed. These vectors were used to clone random B. fragilis promoters from partial genomic libraries and the recombinants displayed a range of CAT activities and chloramphenicol MICs in B. fragilis hosts. In addition, known E. coli promoters (Ptet, Ptac, Ptrc, Psyn, and P1P2rrnB) were tested for activity in B. fragilis. No chloramphenicol resistance or CAT activity was observed in B. fragilis with these promoters. PMID- 1615065 TI - Mobilization of recombinant plasmids from Staphylococcus aureus into coagulase negative Staphylococcus species. AB - pC221, a small nonconjugative staphylococcal plasmid, can be mobilized between staphylococci by pG01, a larger conjugative plasmid. pC221 carries the two transacting genes, mobA and mobB, which are needed for its mobilization. The products of these genes create a site-specific single-stranded nick (mobA) and then facilitate DNA transfer (mobB). Several useful Escherichia coli staphylococcal shuttle plasmids containing the cloned single-stranded nick site were created and successfully mobilized into Staphylococcus aureus and two coagulase-negative staphylococci, S. epidermidis and S. saprophyticus, by providing mob genes (pC221) and conjugative transfer genes (pG01) in trans in the donor. These vectors may offer a genetic system for the introduction of recombinant plasmids into coagulase negative staphylococci. PMID- 1615066 TI - cis-inhibitory elements in the pT181 replication system. AB - We report here the existence of a pair of sequence elements in plasmid cointegrates that together block the function of pT181 plasmid replication origins in cis. The study is an outgrowth of the use of plasmid pE194 as a vector for the analysis of the pT181 replication system. We have observed that whereas the isolated pT181 replication origin is fully functional when cloned to pE194, it is inactive when the entire pT181 plasmid genome is cloned. This cis inhibition is relieved by deletion of all or part of the pE194 palA element or of the pT181 countertranscript promoter. The inhibitory effect of pE194 palA is independent of distance and orientation, whereas the inhibitory effect of the countertranscript promoter is lost when the promoter is moved to a distance of 1.5 kb from the replication origin or inverted in situ. We found that the cis inhibited pT181 origin expresses origin-specific (Inc3B) incompatibility, which involves competition for the initiator protein. This finding suggests that the cis-inhibited origin binds the initiator protein and therefore that the inhibition affects a step in the initiation process subsequent to initiator binding. PMID- 1615067 TI - Composite rhytidectomy. AB - Signs of aging in the face reflect the change in position of deep anatomic elements, which are the platysma muscle, cheek fat, and the orbicularis oculi muscle. These changes occur from progressive ptosis of these elements, which continue to keep their intimate relationship with each other throughout the aging process. Conventional face lift procedures disrupt this normal relationship by separating the skin from these elements. All SMAS techniques reposition only the platysma muscle without repositioning the cheek fat and orbicularis muscle. This composite rhytidectomy allows elevation of a composite musculocutaneous flap containing all three elements for repositioning while maintaining their intimate relationship with each other and with the skin. One-hundred and sixty-seven composite rhytidectomies have been done with impressive results and minimal complications. PMID- 1615068 TI - Improved salvage of complicated microvascular transplants monitored with quantitative fluorometry. AB - Quantitative fluorometry has been used to monitor circulation in transplanted toes and cutaneous flaps in our unit since 1982. Analysis of 177 uncomplicated transplants monitored by quantitative fluorometry shows that this technique has low false indication rates for arterial occlusion (0.6 percent of patients) and venous occlusion (6.2 percent of patients). None of these patients was reexplored because of a false monitor reading, and except for single abnormal sequences, monitoring appropriately indicated intact circulation throughout the postoperative period. Quantitative fluorometry has correctly indicated vascular complications in 21 (91.3 percent) of 23 transplants over an 8-year period. The salvage rate (85.7 percent) of the fluorescein-monitored reexplored transplants was significantly higher than the salvage rates of similar reexplored transplants not monitored with fluorescein and of reexplored muscle flaps (which cannot be monitored with the fluorometer used at this unit). These clinical data indicate that quantitative fluorometry is a valid and useful postoperative monitor for transplanted toes and cutaneous flaps. PMID- 1615069 TI - Human pressure perception values for constant and moving one- and two-point discrimination. AB - Despite the need to evaluate sensibility for accurate diagnosis and the need to record the degree of sensation achieved in the postoperative period, the clinician has been without the ability to measure human pressure perception accurately. Traditionally, the Semmes-Weinstein monofilaments were used to measure the static one-point discrimination threshold. A new sensory testing instrument, the Pressure-Specifying Sensory Device, was used to obtain normative data from the index and little finger of the dominant hand in 35 people ranging in age from 16 to 83 with no known neurologic impairment. Pressure perceptions for static one- and two-point discrimination (s1PD, s2PD) and moving one- and two point discrimination (m1PD, m2PD) were recorded. The mean values (+/- SD) were 0.13 +/- 0.06, 0.24 +/- 0.12, 0.22 +/- 0.10, and 0.26 +/- 0.13 gm/mm2 for s1PD, s2PD, m1PD, and m2PD, respectively, on the index finger and 0.07 +/- 0.05, 0.16 +/- 0.12, 0.17 +/- 0.07, and 0.21 +/- 0.14 gm/mm2 for s1PD, s2PD, m1PD, and m2PD, respectively, for the little finger. The little finger was significantly more sensitive than the index finger (p less than 0.001). There was no significant change in pressure perception with increasing age. PMID- 1615070 TI - What will historians say? PMID- 1615071 TI - Who's first on first? PMID- 1615072 TI - Cancer recurrence following Mohs micrographic surgery: a mechanism of tumor persistence. AB - Recurrence of basal cell carcinomas after Mohs micrographic surgery is rare but known to occur. This report describes the recurrence of a basal cell carcinoma of the forehead after Mohs surgery in order to illustrate a previously undescribed mechanism of tumor persistence and recurrence despite thorough microscopic evaluation of all surgical margins. The value of the surgeon's reviewing all prior histologic sections before performing micrographic surgery, the importance of resecting all scar tissue from a previous surgical site prior to determination of tumor-free margins, and the potential usefulness of a three-tiered closure after excision of a cutaneous malignancy that involves the muscular layer are discussed. PMID- 1615073 TI - Facial midline and symmetry: modified face bow. AB - A facial "cone" can be drawn inside the head. The apex of the cone is the midpoint of the line that connects both ear canals, point C, and the face is the base. A modified face bow is designed with holes through which a Steinmann pin is passed, meeting at the apex of the facial cone. After the ear bolts are symmetrically fixed, the Steinmann pin through the central hole follows the midline of the face as the bow rotates from the forehead to the chin. The right and left facial bony protrusions can be evaluated by two Steinmann pins projecting through the corresponding holes on the face bow. This device is utilized to determine the facial midline and facial symmetry during surgery. It also can be used as a tool for anthropologic studies. PMID- 1615074 TI - Rhinoplasty: the retractable roof. PMID- 1615075 TI - Teeth in the line of a mandible fracture: which should be performed first, extraction or fixation? PMID- 1615076 TI - Secondary healing. PMID- 1615077 TI - Effect of epinephrine on blood loss during liposuction. PMID- 1615078 TI - A report of anatomic variation in the rat femoral vein. PMID- 1615080 TI - Faulty planning in plastic surgery. PMID- 1615079 TI - Sterility of bone pencils. PMID- 1615081 TI - Repositioning the orbicularis oculi muscle in the composite rhytidectomy. AB - While blepharoplasties are routinely done with face lift procedures, the improvement is accomplished by removing excess orbital fat with eyelid skin and muscle along the incisional line. The orbicularis oculi muscle remains intact as its inferior border, which has become ptotic and redundant with aging, and actually remains in the same position following a conventional lower lid blepharoplasty and rhytidectomy. However, by elevating the orbicularis oculi with the cheek fat and platysma in a composite face lift flap, and by excising the redundant inferior border of the orbicularis muscle, a total rejuvenation of the malar area is accomplished. The descent of the orbicularis oculi muscle is in an inferolateral vector, whereas the vector of facial aging is inferomedial. Thus, repositioning the orbicularis oculi is in a superomedial vector and is obligatory in a composite rhytidectomy. PMID- 1615082 TI - Health care for Americans. PMID- 1615084 TI - An easy method of tunneling pedicle flaps. PMID- 1615083 TI - Avoiding needle sticks in the operating room. PMID- 1615085 TI - MRI and capsular contracture. PMID- 1615086 TI - Locating tissue expander injection ports with a metal detector. PMID- 1615087 TI - Avoidance of a double digital nerve graft as a secondary procedure in revascularization patients. PMID- 1615088 TI - Neuroblastoma presenting as a craniofacial deformity. PMID- 1615089 TI - Alar rim raising. AB - The relationship of the alar rim to columella visibility and nostril proportion is crucial to a good aesthetic result. The alar rim has been a neglected part of the nose in primary and secondary rhinoplasty procedures for want of a natural contouring operation. Results of directly excising the alar rim and its indications are presented with adequate follow-up. Indications for the procedure include (1) recontouring of the cleft lip nose with anterior webbing, (2) equalizing asymmetrical nostrils, (3) enlarging small nostrils, (4) correcting a hanging (sigmoid) ala, and (5) converting round to oval nostrils. PMID- 1615090 TI - Arterial supply of the anterior ear. AB - Twenty cadaver auricles were injected with a latex solution to define the arterial supply of the anteroauricular surface. Two arterial networks exist, the network of the triangular fossa-scapha and the network of the concha. Both eventually communicate on the anthelix. The triangular fossa-scapha network originates from one subbranch of the upper auricular branch of the superficial temporal artery and from branches of the posterior auricular artery that come through the earlobe and triangular fossa and over the helical margin. The conchal network is provided by two to four perforators that come from the posterior auricular artery, piercing the conchal floor. Auricular branches of the superficial temporal artery in the preauricular region and their communications with the posterior auricular artery also were confirmed. We believe that a greater understanding of the detailed arterial anatomy in this area allows one to develop safely a variety of surgical techniques for reconstruction of the ear. PMID- 1615091 TI - Patch esophagoplasty with free forearm flap for focal stricture of the pharyngoesophageal junction and the cervical esophagus. AB - Focal stricture of the cervical esophagus can be caused by corrosive injury or irradiation or following esophageal reconstruction. For severe stricture that cannot be relieved by bougie dilatation, surgical correction should be done. Among the operations performed, the myocutaneous flap is considered the first choice. Patch esophagoplasty with a free flap is indicated in the following situations: (1) when the patient is a young woman, (2) when the patient is obese, and (3) following irradiation that renders myocutaneous flaps unreliable. For correction of focal stricture of the cervical esophagus, six patients underwent esophagoplasty with a patch of free forearm flap. In comparison with other methods, this approach is associated with less morbidity and a better aesthetic result. The patients started oral intake at 1 month. Only one patient had minor leakage, and this healed after conservative treatment. The skin patch inserted in the esophageal wall caused no problem in motility, and the patients could eat smoothly after surgery. PMID- 1615092 TI - Congenital malignant melanoma. AB - The diagnosis and management of a 3-day-old infant with an exophytic pigmented growth on her back and chest are discussed. At 3 days of age, the child underwent a complete surgical excision of this lesion with immediate coverage by partial thickness skin grafts. Pathologically, the lesion proved to be a thoracolumbar congenital melanocytic nevus with multiple focal areas of malignant melanoma. The child is now 3 years past surgery and shows no evidence of recurrence or distant metastases. The importance of this case lies in the presence of overt malignant melanoma at birth within a giant congenital nevocytic nevus. PMID- 1615093 TI - The impact of stress on the clinical presentation of melanoma. AB - The impact of major life events on the clinical presentation of melanoma was determined in a retrospective case-control analysis. There was a significantly higher occurrence of divorce or marital separation and a significantly higher occurrence of bankruptcy or unemployment in the 5 years prior to the clinical presentation of 56 melanoma patients relative to an age- and sex-matched control group of 56 general surgical patients (p less than 0.01). There was also a higher occurrence of death of a spouse or immediate family member, although this difference was not statistically significant. Overall, 26 (46 percent) of the melanoma patients had major life crises in the 5 years prior to clinical presentation, and this was highly significant (p less than 0.01). We believe that major life stress has an impact on the clinical presentation of melanoma. Potential reasons for this difference are reviewed. PMID- 1615094 TI - Reduction mammaplasty with a circular folded pedicle technique. AB - A personal technique for breast reduction utilizing a circular dermal-breast pedicle is presented. After a cutaneous glandular excision in the inferior pole and glandular excision in a discoid shape under the central area, the pedicle is folded on itself to produce a direct elevation of the nipple-areola complex into its new position, to enhance projection, and to act as a central support. A rational economy of scars is obtained by a central convergence of the breast tissue that stretches the breast periphery and by sutures finishing in the inferoareolar area. There the skin excess is removed to avoid scar lengthening in both the caudal and cranial directions. Evaluation of long-term results reveals maintenance of breast projection, preservation of the inframammary fold to inferior areola distance, and minimal residual scarring. PMID- 1615095 TI - The biomechanical and histopathologic effects of surface texturing with silicone and polyurethane in tissue implantation and expansion. AB - There has been considerable interest in determining the effect of morphologic alterations of prosthetic surfaces on capsule response in breast surgery. The purpose of this study was to provide a precise, three-dimensional evaluation of soft-tissue response to surface modifications in both implantation and expansion. Expandable 100-cc prostheses were designed with one of three surfaces: textured silicone (Biocell), standard smooth silicone, or polyurethane (Natural-Y, Meme). A new submuscular implantation site in the rabbit was developed. Each animal randomly received a smooth-surface device on one side and either a textured silicone or polyurethane device on the other. In one group of animals, the prostheses were expanded monthly. Capsular response was evaluated monthly in vivo using standardized techniques as well as biomechanical methods for up to 6 months in the expander group (n = 7 to 16) and 8 months in the implant group (n = 7 to 15). Analysis of biomechanical and histologic data revealed that prosthetic surface morphology can specifically alter capsular response. Polyurethane was the only effective surface in preventing capsular contracture in implantation. In expansion, both textured silicone and polyurethane surfaces resulted in significantly less capsular contracture and less resistance to expansion than comparable smooth-surfaced controls. Statistical comparisons reveal that the biomechanical methods utilized in this study provide the most precise and objective method of defining overall soft-tissue contracture around implanted biomaterials. PMID- 1615096 TI - Free flaps in the elderly. AB - Microsurgical transfer of tissue has become a primary tool of the reconstructive surgeon. The elderly, as a growing segment of our society, are requiring free tissue transfers in proportion to their numbers. To investigate the potential morbidity of free-tissue transfers in the elderly, we studied consecutive populations of 31 patients above the age of 65 years and 90 patients below the age of 65 years. Complication rates were 65 and 49 percent, respectively. Premorbid medical conditions were present in 87 percent of patients 65 years and older and in 72 percent of those under 65 years. Medically related complications in free-tissue transfers, previously unreported in the literature, were 35 percent in the elderly group and 10 percent in the younger group. Wound-healing complications were seen in equal proportions between groups. The rates of wound and medically related complications observed in the elderly group were nearly double those observed in the younger group; however, after correction for the presence of preexisting medical conditions, no significant differences were seen between the two groups. These observations suggest that age alone is not a variable in risk for free-tissue transfers. Elective microsurgery can be performed in the elderly patient with a high expectation of success. PMID- 1615097 TI - Microcirculatory disturbances following the passage of emboli in an experimental free-flap model. AB - Following completion of arterial repair in an experimental free-flap model, platelet emboli have been observed passing through the microcirculation downstream. The purpose of this experimental study was to observe and quantitate changes in capillary perfusion occurring subsequent to these events. The isolated rat cremaster model was used. For 6 hours subsequent to surgical injury of the main artery in this model, the number of emboli and the number of perfused capillaries downstream were counted. In eight rats having an intentional arterial wall injury, emboli were consistently seen during the first hour of reflow. In the nine control animals having no arterial injury, no emboli were seen. The presence of emboli in the cremaster muscle, resulting from the arterial injury, was associated with a significant reduction in the number of perfused capillaries. We suggest that the observed decrease in capillary perfusion was associated with microemboli that produced an adverse effect for several hours after their initial presence in the circulation. PMID- 1615098 TI - Will schizophrenia become a graveyard for molecular geneticists? PMID- 1615099 TI - Genetics and developmental stability: an integrative conjecture on aetiology and neurobiology of schizophrenia. PMID- 1615100 TI - Lasegue's editorial riposte to Gull's contributions on anorexia nervosa. AB - One week after Sir William Gull read his seminal report on anorexia nervosa to the Clinical Society of London, a brief account was published (Anonymous, 1873). In Paris, Charles Lasegue, editor of Archives Generales de Medecine read the report and printed an immediate editorial riposte, parts of which will be quoted in this communication. PMID- 1615101 TI - Subjective response to neuroleptics and outcome in schizophrenia: a re examination comparing two measures. AB - The schizophrenic patient's early psychological response to neuroleptic treatment has been demonstrated to be a significant predictor of treatment response. The validity of the construct of subjective response is evaluated by comparison of two measures. Fifty-five recently admitted and unmedicated schizophrenic patients were randomly allocated to chlorpromazine or haloperidol. Subjective responses at 24 and 48 hours as assessed by two different scales, the Van Putten & May scale and the self-administered Drug Attitude Inventory, were strongly correlated with outcome at three weeks. Early emergence of extrapyramidal symptoms was not related to subjective response, but dysphoric patients had a greater incidence of EPS by the end of treatment than did non-dysphoric patients. The two measures showed high concordance in identification of early drug dysphoria. PMID- 1615102 TI - Frontal and non-frontal lobe neuropsychological test performance and clinical symptomatology in schizophrenia. AB - Schizophrenic subjects performed significantly worse on neuropsychological tests of frontal lobe function but not on tests of non-frontal lobe function when compared to a matched group of normal subjects. Correlations expected between frontal lobe neuropsychological test performance and negative symptoms were not found. PMID- 1615103 TI - Comparison of negative symptoms in schizophrenic and poor outcome bipolar patients. AB - Using the Scale for the Assessment of Negative Symptoms (SANS), affective blunting, alogia, and attentional impairment were assessed in 30 manic patients with chronic impairment of inter-episode instrumental functioning and 85 chronic schizophrenic patients. The schizophrenic patients had markedly higher ratings on all three negative symptom dimensions. When negative symptoms were examined categorically, no manic patient was rated to show prominent affective flattening or alogia. This relative specificity may not apply to attentional impairment which was rated as prominent in 17% of the manic patients and in 55% of the schizophrenic patients. PMID- 1615104 TI - Diagnostic concordance in functional psychosis revisited: a study of inter relationships between alternative concepts of psychotic disorder. AB - More than a decade ago, a series of retrospective studies examined the concordance between proliferating definitions of severe psychiatric disorder. The European response has been a poly-diagnostic one, which has attempted to maintain interest in a broad range of psychiatric phenomena in the psychoses. In North America a more convergent approach has emerged, resulting in a series of operational definitions evolving from one another, and a correspondingly limited capacity to allow alternative perspectives to co-exist. The present study uses a prospective design as well as recent improvements in the clinical validity of psychopathology assessment to re-evaluate the relationships between competing concepts of psychotic illness in a broad sample (N = 176) of recent-onset psychotic patients. In the schizophrenic group, concordance was predictably highest among recent North American 'cousins', and lowest among various historical concepts. There was a moderately high concordance between selected schizoaffective and atypical psychosis definitions, indicating that this component is an important area for further studies of descriptive validity. These interrelationships may be used as a starting point to explore latent classes underlying the phenomena of functional psychosis. PMID- 1615105 TI - Comorbidity of substance abuse and schizophrenia: the role of pre-morbid adjustment. AB - Co-morbid substance use and abuse is common in schizophrenic patients, and the role of substance abuse in initiating and maintaining psychosis has important definitional and aetiological implications. We investigated the issue in a cohort of 131 schizophrenic patients. We found non-users (N = 67) were similar to pathological users (N = 64) in current symptomatology and clinical history. The pathological users did, however, have better pre-morbid adjustment levels. Only alcohol use and to some extent cannabis use contributed to this effect; use of stimulants or hallucinogens did not. These results indicate the importance of evaluating the various types of substance used when attempting to explore the significance of co-morbidity. The results also suggest that co-morbidity of substance abuse and schizophrenia may be explained by a common factor antecedent to both: better pre-morbid adjustment. A two-stage model is proposed to explain these findings: increased sociability increases exposure to opportunities of substance use in a subset of patients; subsequent onset of psychotic illness accelerates the use to a pathological level as the individual attempts to cope with the stress of the developing mental illness. PMID- 1615106 TI - Cognitive deficit and the prediction of rehabilitation success in a chronic psychiatric group. AB - This paper describes the second stage (years 4, 5 and 6) of a prospective follow up of a sample of chronic patients which was designed to investigate the in service use. It also tested the relative predictive power of variables which included demographic, symptomatic and behavioural factors as well as a novel reaction time variable which reflects response processing time. During the six years of the study 91% of the patients in the sample changed either the degree of their day and/or night care. Many moved to more independence but, a number did also become more dependent on psychiatric services. There were no differences in outcome between a schizophrenic group and patients with other diagnoses. These results suggest a level of flexibility in outcome even in a severely disabled chronic group. The main predictor of future service use at each stage of the follow-up for the whole group was chronicity at entry to the study. But, when the group was divided into schizophrenic patients and 'others', the response processing measure was a significant predictor of service use in the schizophrenic group and accounted for between 17% and 30% of the variance. For the 'other' diagnostic group, the age of the patient seemed to be the major determinant of care. The reaction time variable seems to be an extra class correlate of a strict diagnosis of schizophrenia. It may also be a stable or episodic vulnerability factor, but as well as these promising hypotheses, which have yet to be justified, this measure does seem to have pragmatic value in predicting outcome in a rehabilitation network. PMID- 1615107 TI - Autobiographical memory and problem-solving strategies of parasuicide patients. AB - Recent research has noted the tendency of parasuicide patients to retrieve over general autobiographical memories. Separate studies suggest problem-solving deficits within this group. The present study was concerned first with replicating these findings and, secondly, with developing a model of the relationship between over-general memory recall and poor problem-solving abilities in parasuicide patients. Anger and hopelessness were measured as markers for mood. In line with the hypotheses, the parasuicide group (N = 12) produced significantly over-general memories in contrast to a matched control group (N = 12). This occurred significantly in relation to positive cues, and latency to first responses was significantly delayed in the parasuicide group. The parasuicide group also provided fewer and less-effective problem-solving strategies than the control group, and a significant association was found between low effectiveness of problem-solving strategies and over-general memory recall in the parasuicide group. Anger and hopelessness levels were significantly higher within the parasuicide group in line with previous findings. The clinical implications of these findings are discussed. PMID- 1615108 TI - Railway suicide: the psychological effects on drivers. AB - People have jumped (or fallen) in front of trains on the London Underground system in increasing numbers throughout the twentieth century. During the past decade there have been about 100 such incidents each year, of which around 90 would involve the train driver witnessing his train strike the person on the track. Most are suicides or attempts at suicide. They represent major unexpected and violent events in the lives of the train drivers and it might be expected that some of them would respond by developing a post-traumatic stress reaction of the type identified by Horowitz (1976) or other adverse psychological reactions or both. The research reported in this paper was designed to characterize the range of responses of drivers to the experiences of killing or injuring members of the public during the course of their daily work. It was found that 16.3% of the drivers involved in incidents did develop post-traumatic stress disorder and that other diagnoses, e.g. depression and phobic states, were present in 39.5% of drivers when interviewed one month after the incident. PMID- 1615109 TI - Psychosocial correlates of clinical depression after psychiatric in-patient treatment: methodological issues and baseline differences between recovered and non-recovered patients. AB - General methodological and design issues in research on psychosocial outcome predictors of clinical depression are discussed, and the first stage of a study of discharged depressed in-patients is presented. It involved 115 recovered and 75 non-recovered such patients who were compared regarding stress factors, social support, personality and coping styles. While there were few differences between recovered and non-recovered patients with respect to stable personality traits, recovered patients were less likely to have had severe long-term life difficulties, and their coping style differed: it was characterized by more negative appraisals of stressful situations, greater problem avoidance, less palliative activities, and a lesser inclination to solicit social support. Whereas among women without partners, as well as men, non-recovery was also associated with less support from friends, in particular psychological-emotional support in crises, non-recovered women with partners had much more such support. The results are discussed with reference to the existing literature on outcome correlates of clinical depression. PMID- 1615110 TI - Environmental risk factors for Alzheimer's disease: their relationship to age of onset and to familial or sporadic types. AB - Data from a case-control study of Alzheimer's disease (AD) were analysed in relation to age of onset and familial/sporadic status. The analyses were restricted to environmental exposures which might injure the brain. Later-onset AD was found to be positively associated with starvation/malnutrition and with nose-picking and negatively with analgesics, while earlier-onset was associated with physical underactivity and nervous breakdown more than 10 years before. Sporadic AD was associated with starvation/malnutrition and with head injury. These analyses merit replication in other large case-control studies of AD. PMID- 1615111 TI - Longitudinal analysis of a two-component model of the memory deficit in Alzheimer's disease. AB - The memory deficit in Alzheimer's disease (AD) has been characterized as consisting of multiple components. The purpose of this study was to confirm the utility of a two-process model, and to examine changes in the nature and extent of the neuropsychological deficits after a one-year interval. The results replicate the initial observation that the memory loss in AD can be described as consisting of a focal amnesic syndrome and a dysexecutive syndrome characterized by failure of rapid information processing and search of both episodic and semantic memory. One year after the initial observation, all dysexecutive patients and the majority of the amnesic patients had become non-focal. No patient developed a dysexecutive syndrome, but 18 patients developed amnesic syndromes. These results suggest that, like other aspects of the cognitive deficits of AD, the memory loss is multifactorial. These results have implications for understanding the pathophysiology of AD, and for designing pharmacotherapeutic intervention. PMID- 1615112 TI - Coping strategies and breast disorders/cancer. PMID- 1615113 TI - Measuring psychiatric disorder in the recent past: the use of the Psychiatric Assessment Schedule retrospectively. AB - Ninety-four patients were asked about the presence of psychiatric symptoms on admission to hospital using the revised Psychiatric Assessment Schedule. Three months later they were asked to recall their symptoms at admission using the same instrument retrospectively. The results of the initial and retrospective interviews showed good rates of agreement in terms of PAS score, ID level, psychiatric 'caseness' and both CATEGO and DSM-III-R diagnoses. The study demonstrates that it is possible to make reliable measurements of the mental status of three months previously, simultaneously with assessments of current mental status. The uses of such a measuring instrument are discussed. PMID- 1615114 TI - Measuring psychiatric disorder in the community: a standardized assessment for use by lay interviewers. AB - Many of the standardized interviews currently used in psychiatry require the interviewer to use expert psychiatric judgements in deciding upon the presence or absence of psychopathology. However, when case definitions are standardized it is customary for clinical judgements to be replaced with rules. The Clinical Interview Schedule was therefore revised, in order to increase standardization, and to make it suitable for use by 'lay' interviewers in assessing minor psychiatric disorder in community, general hospital, occupational and primary care research. Two reliability studies of the revised Clinical Interview Schedule (CIS-R) were conducted in primary health care clinics in London and Santiago, Chile. Both studies compared psychiatrically trained interviewer(s) with lay interviewer(s). Estimates of the reliability of the CIS-R compared favourably with the results of studies of other standardized interviews. In addition, the lay interviewers were as reliable as the psychiatrists and did not show any bias in their use of the CIS-R. Confirmatory factor analysis models were also used to estimate the reliabilities of the CIS-R and self-administered questionnaires and indicated that traditional measures of reliability are probably overestimates. PMID- 1615115 TI - Why people with probable minor psychiatric morbidity consult a doctor. AB - This epidemiological investigation examines factors determining medical consultation in people with probable minor psychiatric morbidity. About 54% of people with probable minor psychiatric morbidity and about 23% of the (numerically much greater) remainder with lower probability of psychiatric morbidity consulted a doctor, usually a primary care physician, in the two weeks prior to a research interview. Medical consultation rates were higher in females than in males. The dominant finding was that in people with probable minor psychiatric morbidity physical illness was strongly associated with medical consultation. Almost 89% of males and 97% of females with probable minor psychiatric morbidity and physical illness consulted a doctor in the two weeks prior to interview. Logistic regression modelling was used to investigate the joint effects on medical consultation of physical illness and six socio demographic variables, and physical illness emerged as the major single determinant of medical consultation in women and, in men, it exerted its effect through an interaction with lower educational level. PMID- 1615116 TI - The Mental Impairment and Evaluation Treatment Service: staff attitudes and staff client interactions. AB - This study describes and evaluates a new short-term residential service for adults with mild learning difficulties and challenging behaviour, the Mental Impairment Evaluation and Treatment Service. The study examines staff attitudes towards management practices, towards the potential achievement of individuals with learning difficulties, the staff's perceived involvement in decision making, and also the nature of their interaction with the clients, in two different settings on the Unit. The Unit's management practices were found to be client orientated in nature and staff were more in agreement with client-orientated than institution-orientated management practices. Staff were generally optimistic about clients' potential and felt involved in decision making. Correlations between certain staff characteristics, attitudes and interactions are discussed. The study extends the range of services that have been evaluated in this way, and provides a description of the service in its early stages, which will provide an important comparison point for it when it is more permanently established. PMID- 1615117 TI - Rapid development of hyponatraemic seizures in a psychotic patient. AB - A 60-year-old woman with a history of recurrent psychotic illness developed severe hyponatraemia after a short period of compulsive water drinking. The case provides a rare illustration of the rapidity of development of dangerously low levels of serum sodium. On discovery of mild hyponatraemia it is essential to repeat measurement of the serum sodium level should the patient's clinical condition change, in order to detect any further deterioration of serum osmolality which may result in severe and possibly fatal cerebral symptoms. PMID- 1615118 TI - Structural brain imaging abnormalities associated with schizophrenia and partial trisomy of chromosome 5. AB - Chromosomal abnormalities occurring in association with mental illness provide a unique opportunity to study the interaction of genetic abnormalities and the brain in mental illness. Four individuals from a family in which schizophrenia was found to cosegregate with a partial trisomy of chromosome 5 were studied with computed tomography and magnetic resonance imaging. Temporal lobe atrophy was found in the two trisomic males and in the asymptomatic balanced translocation female. In addition, a large cavum septum pellucidum and a cavum vergae were found in the older trisomic individual. Scans from the normal male were free of abnormalities. These results suggest that molecular studies of the translocation breakpoints in this chromosomal abnormality may be of interest, and encourage further studies of brain structure in other chromosomal abnormalities associated with psychosis. PMID- 1615119 TI - Behavioral screening for cognition enhancers: from indiscriminate to valid testing: Part I. AB - Preclinical efforts to detect and characterize potential cognition enhancers appear to have been dominated by a strategy of demonstrating a wide variety of apparently beneficial behavioral effects with little attention given to the specific psychological mechanisms underlying behavioral enhancement. In particular, the question of whether or not behavioral facilitation is based on relevant mnemonic mechanisms and is independent of the stimulus properties and/or the motivational and attentional components of a task is not often considered. As a result, an overwhelming number of compounds have failed to produce the clinical effects predicted for them on the basis of preclinical research. The available data suggest that a more successful approach requires deductive research strategies rather than the indiscriminate accumulation of apparently beneficial effects in a variety of behavioral tasks and animal models. The first step towards such an approach is a systematic and rigorous evaluation of the different aspects of validity for the models most frequently used in preclinical research. It is concluded that a combination of good construct validity and good face validity represents a necessary condition for screening tests with predictive validity, and that the most popular paradigms fail to fulfil these criteria. Future screening programs for cognition enhancers will probably be characterized by a depreciation of "fast and dirty tests" in favor of approaches focussing on the validity of the effects of potential cognition enhancers. PMID- 1615121 TI - Pavlovian conditioning of L-dopa induced movement. AB - Using the unilateral 6-hydroxydopamine (6-OHDA) substantia nigra pars compacta (SNC) lesion rat model and a Pavlovian conditioning protocol, the present investigation determined that the contralateral rotation response induced by the antiparkinsonian dopaminergic drug L-dopa can become conditioned to exteroceptive test environment stimuli. Two non-drug conditioning tests indicated that contralateral rotation was elicited by the test environment without the presence of L-dopa. This conditioned response had a rotation diameter profile that was qualitatively the same as the L-dopa induced contralateral rotation response. Additionally, drug tests with the combined dopaminergic receptor antagonists, SCH 23390 (0.1 mg/kg) and haloperidol (0.5 mg/kg), at doses sufficient to block spontaneous behavior and L-dopa (20 mg/kg)-induced rotation, revealed that the conditioned contralateral rotation response, unlike L-dopa-induced contralateral rotation, is not affected by D1/D2 receptor blockade. Thus, the conditioned stimuli of the test environment can elicit the contralateral rotation response even in animals rendered akinetic by D1/D2 antagonists. This activation of a conditioned dopaminergic drug response by the situational stimuli, independent of dopaminergic mechanisms, may, therefore, contribute to the untoward overstimulation clinical effects of L-dopa through summation of conditioned and drug-induced effects. Furthermore, the use of conditioning procedures to elicit movement in akinetic animals may provide a new research methodology to investigate the phenomenon of paradoxical kinesia. PMID- 1615122 TI - Behavioral economics of drug self-administration. IV. The effects of response requirement on the consumption of and interaction between concurrently available coffee and cigarettes. AB - In behavioral economics, consumption of a reinforcer is determined by its price and by the price of other available reinforcers. This study examined the effects of price manipulations on the consumption of concurrently available coffee and cigarettes. During fifteen 4-h sessions, coffee and cigarettes were concurrently available according to fixed-ratio (FR) schedules of reinforcement. After consumption stabilized under a fixed ratio 100 for both reinforcers, the response requirement for each reinforcer was varied separately (i.e., FR 100, 1000 and 2500), while the response requirement for the other reinforcer was kept at 100. Increasing the FR value decreased coffee and cigarette consumption to a similar degree. Also, as the price for cigarettes increased (and consumption decreased), coffee consumption decreased; however, as the price of coffee increased, cigarette consumption did not change. These results indicate that for this setting the reinforcing effects of cigarettes and coffee were comparable but interacted asymmetrically. These findings when analyzed and quantified via economic concepts of own-price and cross-price elasticity illustrate the viability of using behavioral economics to examine drug self-administration in a choice paradigm. PMID- 1615120 TI - Complex motor and sensorimotor functions of striatal and accumbens dopamine: involvement in instrumental behavior processes. AB - The suggestions that dopamine (DA) systems are involved in "motor control" and "reward" represent the classic working hypotheses on the behavioral functions of these systems. The research generated by these hypotheses has yielded results that are far more complicated than the simplest form of either hypothesis would indicate. Pharmacological or lesion-induced interference with DA function does not suppress all aspects of movement control, nor all aspects of reward, nor all aspects of motivation. The deficits produced by interference with DA systems are selective and dissociative in nature, affecting some aspects of motor or motivational function, but leaving others basically intact. In some sense the hypotheses that DA is involved in "motor" or "reward" or "motivational" processes are partly correct, but the processes to which these terms refer are too broad to offer an accurate and detailed description of the behavioral functions of brain DA. A review of the literature on the behavioral pharmacology of DA suggests that the behaviors most easily disrupted by DA antagonists are highly activated and complex learned instrumental responses that are elicited or supported by mild conditioned stimuli, and maintained for considerable periods of time. It is proposed that DA in accumbens and striatum modulates the ability of neocortical and limbic areas involved in sensory, associative, and affective processes to influence complex aspects of motor function, and also modulates the execution of complex motor acts organized by the neocortex. Thus, interference with DA systems produces a "subcortical apraxia", which dissociates complex stimulus processes from complex motor processes, but leaves aspects of those processes intact. PMID- 1615123 TI - Ontogeny of cocaine hyperactivity and conditioned place preference in mice. AB - Conditioned place preference (CPP) procedures using jointly visual and tactile cues (white compartment with a wide-mesh metal floor versus black compartment with a narrow-mesh floor) were employed to assess the ontogenetic pattern of cocaine reinforcing properties in outbred CD1 mice. A classical 11-day-long schedule, in which the drug experience occurred in the initially less-preferred compartment ("biased" procedure, Spyraki 1988), served to study cocaine (0, 1, 5, or 25 mg/kg IP repeated four times at 48 h intervals) during the early postweaning stage (21-32 days). The result was a fully-fledged CPP at all cocaine doses. A subsequent experiment used a shortened (4-day) "unbiased" CPP schedule (animals assigned at random to drug experience in one or the other compartment); this enabled an assessment of the ontogenetic pattern of the drug action (single treatment, same dose range) in pups of both sexes at three different developmental ages (14-17, 21-24, or 28-31 days). At the 25 mg/kg dose, CPP developed in animals of all ages, while the 5 mg/kg dose was effective only in 21 24 day pups and the 1 mg/kg dose was ineffective. No significant sex differences were found, but the use of the unbiased procedure enabled a demonstration of an interaction between treatment, age, and type of CS. At the preweaning stage, CPP was due mainly to an increased preference for the black/narrow-mesh compartment, while at the early postweaning stage it consisted mainly of an increased preference for the white/wide-mesh compartment; at the late postweaning stage the cue and the treatment factor did not interact.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615124 TI - Comparison of error patterns produced by scopolamine and MK-801 on repeated acquisition and transition baselines. AB - An understanding of the differential role of cholinergic and glutaminergic systems may be limited by the failure to move the analysis of learning impairments beyond an assessment of changes in overall accuracy. This paper reports the results of two studies in which the effects in rats of scopolamine (0.5-3.0 mg/kg IP), a cholinergic antagonist, and MK-801 (0.05-0.3 mg/kg IP), an NMDA-receptor antagonist, were compared in two different repeated learning procedures and the nature of the underlying error patterns produced by each was evaluated. The first study examined drug effects upon a repeated sequence acquisition procedure and found that while both drugs decreased overall accuracy in a dose-dependent manner, the predominant error pattern varied significantly with drug; scopolamine primarily produced skipping errors within the sequence, whereas MK-801 more prominently increased perseveration on the first and second members of the sequence. In the second study, which used a repeated transition procedure, both drugs again significantly decreased overall accuracy in a dose dependent manner, but no consistent differences in error patterning produced by the drugs were observed. Thus, while both cholinergic and NMDA systems play a role in learning, the behavioral processes underlying the changes in overall accuracy may differ, as indicated by the differential patterns of errors produced by scopolamine and MK-801 in the repeated acquisition baseline. Furthermore, the observed differences in the underlying behavioral processes of scopolamine and MK 801 in the repeated acquisition but not on the repeated transition procedure suggest that each of the two drugs may affect more than one of the variables controlling behavior, with the relative impact of drug-related changes in controlling variables depending upon the operative contingencies of the learning task. PMID- 1615125 TI - Behavioral microanalysis of spatial delayed alternation performance: rehearsal through overt behavior, and effects of scopolamine and chlordiazepoxide. AB - Rats were trained in an operant spatial delayed alternation task utilizing retention intervals from 2 to 32 s. In addition to response accuracy, operations of the levers during the retention intervals were recorded and analyzed. Animals were tested following the administration of the muscarinic antagonists scopolamine hydrobromide and methylbromide, and the benzodiazepine receptor agonist chlordiazepoxide. In vehicle-treated animals, the relative number of correct responses and correct rehearsal operations (operation of the forthcoming correct lever during retention intervals) varied with the length of the retention intervals, and these measures were correlated. The response rate for rehearsal operations increased with the length of the retention intervals. It is speculated that the delay-dependent increase in response rate reflects an effect of delayed reward that was also associated with a delay-dependent increase in the tendency to alternate between levers. The effects of delay on the accuracy of rehearsal operations may have contributed to the delay-dependent correct responding. Scopolamine hydrobromide (0.01, 0.03, 0.1, 0.3 mg/kg) and methylbromide (0.1, 0.3 mg/kg) impaired correct responding, but did not seem to interfere with the relative number of correct rehearsal operations. As only the presentation of the panel light indicated trial onset, it is speculated that the cholinergic receptor blockade resulted in an increase in the probability of a repositioning response that was triggered by light onset. Chlordiazepoxide (1, 3, 5, 10 mg/kg) did not affect behavioral performance. These results suggest that in tasks that allow the development of rehearsal operations, delay-dependent response accuracy does not represent a sufficient condition for conclusions on task demands on memory.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615126 TI - Preexposure to amphetamine and nicotine predisposes rats to self-administer a low dose of cocaine. AB - The acquisition of low-dose (0.25 mg/kg/infusion) intravenous cocaine self administration was measured in rats that had received nine daily injections of amphetamine (1.0 mg/kg, IP), nicotine (0.6 mg/kg base weight, SC) or vehicle. For control rats, the acquisition of self-administration was gradual with the number of responses per 2 h daily test session increasing between days 3 and 9. By comparison, rats preexposed with amphetamine and nicotine demonstrated elevated response means during the early days of testing, suggesting more rapid acquisition. All groups eventually reached similar asymptotic levels of responding. The enhanced responding observed during the early days of testing in the rats preexposed with amphetamine and nicotine was due to an increased number of subjects that reliably self-administered cocaine. Thus, the rats preexposed with amphetamine and nicotine seemed predisposed to the reinforcing effects of cocaine. In contrast to the self-administration data, preexposure to nicotine failed to sensitize rats to the locomotor activating effects of cocaine. In fact, the same preexposure regimen appeared to produce tolerance to this effect of cocaine. These data give evidence that different mechanisms may mediate sensitization to the reinforcing and locomotor activating effects of cocaine. PMID- 1615127 TI - The mesolimbic dopaminergic system is implicated in the reinforcing effects of nicotine. AB - Rats were trained to self-administer nicotine on a fixed-ratio schedule of reinforcement. Infusion of the nicotinic antagonist chlorisondamine into the cerebral ventricles produced a sustained reduction in nicotine self administration compared to vehicle-treated controls. Lesions of the mesolimbic dopamine system were produced by microinfusion of 6-hydroxydopamine into the nucleus accumbens. Following production of the lesions, nicotine self administration was markedly reduced for the 3-week test period; motor impairment did not appear to be responsible. Post mortem analysis of brain tissue showed that the lesion produced a pronounced decrease in dopamine content of the nucleus accumbens and the olfactory tubercle, and a small depletion in the striatum. These data demonstrate that the reinforcing effects of nicotine occur within the central nervous system, and that the mesolimbic dopamine projection plays an important role in these effects. PMID- 1615128 TI - Sensitization to haloperidol-induced suppression of milk intake: effect of interdose interval. AB - The purpose of this study was to determine the effect of manipulating the interdose interval (IDI) on the suppression of milk intake induced by haloperidol (HAL). Groups of rats were given chronic injections of either HAL (0.625 mg/kg) or saline at IDIs of 1, 2, 7, or 14 days. Dose-response curves were determined at the conclusion of the chronic phase. The results indicated that injections of HAL given at IDIs of 1 or 2 days produced neither tolerance nor sensitization, whereas injections given at intervals of 7 or 14 days produced sensitization. Sensitization was also observed in the control groups, perhaps as a result of the intermittent schedule of HAL injections given during the dose-response tests. Sensitization to HAL was not accompanied by changes in sensitivity to amphetamine. The results of this experiment are consistent with those of other studies in showing that the behavioral effects of neuroleptics are strongly influenced by the schedule of injections. In addition, evidence is presented that sensitization to HAL-induced hypophagia is contingent on behavioral experience under the drug. PMID- 1615129 TI - Heightened aggressive behavior during morphine withdrawal: effects of d amphetamine. AB - The morphine withdrawal syndrome is composed of profound short- and long-term changes in autonomic, somato-motor and affective functions. In mice, morphine withdrawal produces heightened aggressive behavior and alterations in motor behavior; however, it is unclear whether these changes in behavior occur in unison and are dependent on a common mechanism or occur independently. In order to characterize the morphine withdrawal syndrome in mice, male Swiss-Webster mice were housed with female partners for 3-4 weeks before being implanted subcutaneously with morphine or placebo pellets. The pellets were removed 72 h after implantation and behavioral measurements were conducted 5, 48 and 96 h after pellet removal. During these tests, mice received d-amphetamine (0.3-10 mg/kg) or saline after which they were assessed for changes in motor behavior and for changes in aggressive behavior while confronting a group-housed male "intruder". In morphine-withdrawn mice, frequency of attack behavior was increased by approximately 30% and this effect persisted for at least 4 days. In contrast, explosive jumping was increased and walking and rearing were greatly decreased at the onset of the withdrawal period but declined within the first 24 h and returned to control levels within 48 h of pellet removal. d-Amphetamine maintained the elevated level of aggressive behavior and sharply increased locomotion in morphine-withdrawn mice; in placebo-pelleted mice, d-amphetamine dose-dependently decreased aggressive behaviors while increasing locomotion. The differential time course and the differential modification by d-amphetamine suggest that heightened aggressive behavior is a long-lasting consequence of morphine-withdrawal based on separate mechanisms than the short-lived alterations in motor activity. PMID- 1615130 TI - A comparison of the effects of sibutramine hydrochloride, bupropion and methamphetamine on dopaminergic function: evidence that dopamine is not a pharmacological target for sibutramine. AB - Sibutramine hydrochloride, a novel monoamine reuptake inhibitor antidepressant, has been studied to determine whether it alters dopaminergic function in the brain. Its effects have been compared with bupropion, a dopamine reuptake inhibitor, and methamphetamine, a dopamine reuptake inhibitor and releasing agent. Sibutramine (0.1-3 mg/kg PO) and methamphetamine (0.3-30 mg/kg PO) both prevented reserpine (0.75 mg/kg IV) ptosis in rats with ED50 values of 0.6 mg/kg and 4.2 mg/kg, respectively. Bupropion (10-100 mg/kg PO) was ineffective against reserpine ptosis. The efflux of [3H]-dopamine from preloaded rat striatal slices was not altered by 10(-7)-10(-5) M concentrations of sibutramine, BTS 54,354, BTS 54,505 (secondary and primary amine metabolites, respectively) or bupropion. In contrast, methamphetamine (10(-8)-10(-4) M) caused a significant concentration dependent increase in [3H]-dopamine release. Sibutramine (3 mg/kg IP or 6 mg/kg PO) and bupropion (10 mg/kg IP or 30 mg/kg PO) did not alter 3-methoxytyramine (3 MT) levels in rat striatum. Striatal 3-MT concentrations were, however, dose dependently increased by methamphetamine (0.3-10 mg/kg IP or 0.42-4.2 mg/kg PO). Sibutramine (6 mg/kg PO) did not induce circling in rats with unilateral 6 hydroxydopamine lesions of the nigrostriatal dopaminergic neuronal tract. Bupropion (10-100 mg/kg PO) did not induce circling at the lowest dose, but caused increasing ipsilateral rotation at higher doses. Methamphetamine (0.42 or 4.2 mg/kg PO) induced ipsilateral circling with marked effects at the higher dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615131 TI - Reinforcing effects of enantiomers of N,N-dimethylamphetamine in squirrel monkeys. AB - Reinforcing effects of the (+)- and (-)-enantiomers of N,N-dimethylamphetamine, a drug that is abused in humans, were studied in squirrel monkeys (Siamiri sciureus) trained under schedules of intermittent cocaine reinforcement. During training, each 30th response produced an injection of cocaine (fixed-ratio schedule), which was followed by a 1-min period during which lights were out and responses had no scheduled consequences (timeout). Sessions in which cocaine injections were scheduled alternated in an irregular sequence with sessions in which saline injections were scheduled. After training, response rates were well maintained by cocaine (response rates approximated 1.4 responses per second) but occurred relatively infrequently during sessions in which saline was injected (response rates approximated 0.3 responses per second). Doses of 10 to 56 micrograms/kg/injection of (+)-N,N-dimethylamphetamine maintained rates of responding significantly higher than those maintained by saline. The (-) enantiomer did not maintain rates of responding that were higher than those maintained by saline when tested at doses up to 100 micrograms/kg/injection. These findings support previous results indicating that N,N-dimethylamphetamine will function as a reinforcer in laboratory animals. Further, they suggest that the significant reinforcing activity of this drug is restricted to the (+) enantiomer. PMID- 1615132 TI - Subjective and behavioral responses to intravenous fentanyl in healthy volunteers. AB - Fentanyl is a mu opiate agonist which is occasionally abused by medical personnel who have ready access to the drug. We examined in healthy volunteers (N = 13) the subjective and psychomotor-impairing effects of intravenous fentanyl (0-100 micrograms/70 kg). A randomized, placebo-controlled, crossover design was used in which subjects were injected with 0, 25 (N = 6), 50 and 100 micrograms/70 kg fentanyl in a double-blind fashion. Subjects completed several questionnaires commonly used in abuse liability testing studies before drug injection and at periodic intervals for up to 3 h after drug injection. Subjects also completed several psychomotor tests at these times. Some aspects of psychomotor functioning (e.g., eye-hand coordination) were impaired by fentanyl. Fentanyl produced dose related increases in ratings of "high" and "sedated," but also tended to produce dysphoria and somatic symptomatology. Most subjects reported liking the effects of the two higher doses of fentanyl for at least a brief time after injection, but they varied widely in their linking ratings across the 3-h post-drug injection period. Despite the transient increases in liking ratings, fentanyl did not increase scores on a widely-used measure of drug-induced euphoria (morphine benzedrine group scale of the Addiction Research Center Inventory). The present results suggest that some medical personnel who experiment with fentanyl may like it, and thus be at increased risk for abusing the drug in the future. PMID- 1615133 TI - Effects of fenfluramine and para-chloroamphetamine on sexual behavior of male rats. AB - The present studies have evaluated the effects of pharmacologically induced release serotonin on sexual responses of male rats during exposure to a sexually receptive female rat. Following acute administration of fenfluramine or para chloroamphetamine (PCA), significant dose-related decreases in copulatory rate and copulatory efficiency, and increases in ejaculatory latency were observed. These effects were not observed when the animals were pretreated with LY53857, a 5-HT1c/2 antagonist. These studies indicate that acute release of serotonin evoked by these releasing agents has inhibitory effects on sexual sexual drive, capacity to achieve erection and threshold for ejaculation, and these effects are mediated by either the 5-HT1c or 5-HT2 receptor. PMID- 1615134 TI - Amphetamine or haloperidol 2 weeks earlier antagonized the plasma corticosterone response to amphetamine; evidence for the stressful/foreign nature of drugs. AB - We inquired whether a single exposure to amphetamine (AM) or haloperidol (HALO) could modify the plasma corticosterone (CORT) response to a second injection of AM 2 weeks later. Male rats were injected with 4 mg/kg d-AM sulfate and tested for water intake for 5 h before sacrifice. Overall, AM induced water intake but none of the pretreatments altered this effect. By contrast, preexposure to AM, HALO or its vehicle 2 weeks earlier prevented the elevation of plasma CORT obtained when AM was administered without pretreatment. A combined pretreatment of HALO or its vehicle with AM produced an even greater blockade of AM-induced CORT elevation. Manipulations which prevented AM-induced drinking reduced the effectiveness of AM pretreatment in attenuating AM-induced elevation in CORT, suggesting that the pretreatment may have been sensitizing the effectiveness of a coping response--drinking--in reducing the CORT effect. Our findings also indicate that a dopamine agonist (AM), a dopamine antagonist (HALO) and a nonspecific stressor (acidic vehicle) can all induce the same, long-lasting action on CORT. This strongly suggests that the effects of AM and HALO in this instance cannot be explained in terms of their pharmacological actions, which are opposite to one another, but instead relate to their properties as stressful/foreign agents to the organism. PMID- 1615135 TI - Effect of taurine on ethanol-induced changes in open-field locomotor activity. AB - In the present investigation we questioned whether taurine antagonized the effects of ethanol on motor activity measured in the open field. Ten minutes following simultaneous administration (IP) of ethanol (1.0, 1.5, 2.0 and 2.5 g/kg) or saline and taurine (30, 45 and 60 mg/kg) or saline, mice were placed in open field chambers and locomotor activity was measured during a 10 min testing period. A significant interaction was found between taurine and ethanol. Taurine treated mice displayed lower motor excitation with the 1.0 g/kg dose of ethanol than the saline group treated with the same dose of ethanol. However at the 2.0 g/kg ethanol dose, taurine-treated mice demonstrated higher motor activity than the saline treated mice, once again, treated with the same dose of ethanol. No differences in blood ethanol levels were observed between the two groups. In a second study, taurine administration (30, 45 and 60 mg/kg) did not show any effect on d-amphetamine-induced enhancement of locomotor activity (1, 2, and 3 mg/kg). Data from this study demonstrated an interaction between taurine and ethanol in their effect on locomotor activity in the open field. PMID- 1615136 TI - Rate of increase of plasma drug level influences subjective response in humans. AB - This study addressed the commonly held, but seldom tested, notion that faster rates of increase of drug effects are associated with more positive subjective effects. Sodium pentobarbital was administered to normal healthy volunteers in either a single oral dose or in a series of divided, cumulating doses, and subjective responses were monitored. Twelve subjects participated in three weekly sessions, during which they received capsules containing placebo, 150 mg pentobarbital in a single dose (SIN) or 180 mg pentobarbital administered in six divided doses (DIV) of 30 mg every 30 min. Doses of pentobarbital in the SIN and DIV were selected to produce similar peak plasma levels. Blood samples were obtained at regular intervals for plasma drug level determinations, and throughout the session subjects completed self-report mood questionnaires (e.g., Profile of Mood States, visual analog ratings of drug liking and drug "high") and psychomotor performance tests (e.g., Digit Symbol Substitution Test). As expected, the SIN and DIV conditions yielded similar peak levels of pentobarbital, but the peak was attained more rapidly in the SIN condition. Despite the similarity in peak plasma levels, subjects reached greater peaks in ratings of "high" and wanted more of the drug when they were in the SIN condition. On an end-of-session liking questionnaire they also reported significantly greater liking of the drug in the SIN condition. On other measures of drug effects (e.g., sedation and psychomotor impairment) no significant differences were observed between the conditions. Thus, the rate of increase of the drug's effects specifically influenced subjects' ratings on subjective measures (e.g., "high" and liking) that may be associated with risk for abuse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615137 TI - Partial reversal of fluoxetine anorexia by the 5-HT antagonist metergoline. AB - Experiment 1 showed that the reduction of intake produced by 5 or 10 mg/kg fluoxetine in rats eating either a solid or a liquid meal was partially antagonised by 1 mg/kg of the 5HT1/5HT2 antagonist metergoline but not by 1 mg/kg of the 5HT2 antagonist ketanserin. Experiment 2 examined the meal patterning of rats given 5 mg/kg fluoxetine and 1 mg/kg metergoline. Fluoxetine alone increased the latency to feed, reduced meal size and shifted the inter-pellet interval (IPI) distribution to the right. Metergoline alone had little immediate effect on food intake or other feeding parameters but partially reversed the reduction of food intake produced by fluoxetine. There was a complete reversal of the increased latency to feed and a partial reversal of the depression of meal size. However, the rightward shift of the IPI distribution caused by fluoxetine, which indicated a depression of feeding rate, was more pronounced after combined treatment. We conclude that fluoxetine reduces food intake by enhancing satiety through a serotonergic dependent mechanism but reduces feeding rate through a separate mechanism, whose neurochemical basis remains to be established. PMID- 1615138 TI - Sodium pentobarbital: sensory and associative effects in classical conditioning of the rabbit nictitating membrane response. AB - Four experiments were conducted to determine the effects of sodium pentobarbital (0, 3, 9, and 15 mg/kg) on the acquisition of the rabbit's classically conditioned nictitating membrane response (NMR) and to determine the locus of the drug's effects on sensory, motor, associative, and nonassociative processes. In experiment 1, classical conditioning of the NMR was accomplished by pairing tone and light conditioned stimuli (CSs) with paraorbital shock as the unconditioned stimulus (US). The experiment revealed that pentobarbital retarded the acquisition of conditioned responses (CRs) to both tone and light CSs. Experiment 2, employing unpaired CS, UCS presentations, indicated small but significant drug effects on NMR base rate and nonassociative NMRs to the CS. Experiment 3 revealed no significant drug effect on the psychophysical functions relating UCS intensity to UCR frequency or amplitude, nor on the UCS intensity threshold for eliciting UCRs. On the other hand, in experiment 4, the drug significantly impaired CR frequency over an extended range of CS intensities and raised CS intensity threshold. It was concluded that pentobarbital's attenuation of CS intensity also operated to impair CR acquisition. PMID- 1615139 TI - L-dopa withdrawal in Parkinson's disease selectively impairs cognitive performance in tests sensitive to frontal lobe dysfunction. AB - A group of ten patients with idiopathic Parkinson's disease (PD) was tested on a series of automated tests of learning, memory, planning and attention whilst either on or off L-dopa medication. Controlled withdrawal of L-dopa interfered with aspects of performance on three of the tests that had previously been shown to be sensitive to frontal lobe dysfunction; a spatial working memory task, the Tower of London planning test, and a visual discrimination paradigm that also included intra- and extra-dimensional shift tests of selective attention. More specifically, errors were increased in the spatial working memory test, and both the accuracy and latency of thinking were impaired. Thinking time was significantly slowed following L-dopa withdrawal, even though the possible contaminating effects on motor slowing were fully controlled by a yoked control procedure. Nine out of ten patients reached a further stage of the visual discrimination, set-shifting paradigm when on, rather than off, L-dopa medication. Spatial span was also impaired off medication, but there were no effects of L-dopa withdrawal on tests of pattern and spatial recognition memory, simultaneous and delayed matching to sample or visuospatial conditional associative learning. Comparisons with a large control group confirmed previous findings that PD is associated with deficits on the majority of these tests. The results are discussed in terms of the fronto-striatal, dopamine dependent nature of some of the cognitive deficits found in PD, but the apparent dopamine independent nature of deficits in other aspects of cognitive functioning, notably in tests of visual recognition memory and associative learning. PMID- 1615140 TI - Abolition of latent inhibition by a single 5 mg dose of d-amphetamine in man. AB - The performance of healthy volunteer subjects on an auditory latent inhibition (LI) paradigm was assessed following administration of a single oral dose of d amphetamine or placebo. It was predicted that a low (5 mg), but not a high (10 mg), dose of d-amphetamine would disrupt LI. The prediction was supported with left ear presentation of the preexposed stimulus only. When the preexposed stimulus was presented to the right ear the predicted pattern of findings was not obtained. It is concluded that the dopaminergic system is involved in the mediation of LI in man and it is speculated that the interaction between amphetamine dose and ear of presentation of the preexposed stimulus may reflect normally occurring dopaminergic hemisphere asymmetry. PMID- 1615141 TI - Hypersensitivity to scopolamine in the elderly. AB - Scopolamine hydrobromide, 0.43 mg/70 kg, was administered by subcutaneous injection to ten young and ten elderly subjects. A comprehensive neuropsychological test battery was used to assess the effects of scopolamine, as compared to placebo, on cognitive function. As previously reported for this group of young subjects, scopolamine significantly impaired performance on tests of recent memory and visuospatial praxis. The same effects were observed in the elderly subjects, but the magnitude of the effects was much larger. The scopolamine injections produced significant psychomotor slowing in the elderly, whereas higher doses of the drug are required to produce this effect in young subjects. In both young and old subjects scopolamine failed to affect immediate memory, language function, object sorting, and the frequency of intrusion errors (although trends toward an effect were more apparent in the elderly). Remote memory, tested in the elderly only, was also unaffected. The results suggest that scopolamine's cognitive effects are quantitatively more pronounced in elderly subjects than young subjects, but that they are qualitatively similar and do not constitute a valid model for the cognitive dysfunction associated with Alzheimer's disease. PMID- 1615142 TI - Suppression of alcohol and saccharin preference in rats by a novel Ca2+ channel inhibitor, Goe 5438. AB - The effect of the novel 1,4-dihydronaphthyridine Ca2+ channel inhibitor Goe 5438 (CI-951) on voluntary ethanol consumption was examined in selectively bred alcohol-preferring (P) rats in a free choice two bottle preference test versus water. Intraperitoneally injected Goe 5438 dose-dependently (5, 10 or 20 mumol/kg, twice daily) inhibited ethanol and increased water intake over the 24 h period (injection day). The drug decreased ethanol preference, originally above 90%, by 6%, 19% and 45% at respective doses, on the injection day. That inhibitory effect of the highest dose of Goe 5438 on ethanol preference remained significant also on days 2 and 3 after injections (-51% and -18%, respectively). Goe 5438, in the highest dose, also tended to decrease granulated chow consumption during the injection day only. To further test whether the inhibition of ethanol preference is secondary to decrease in reinforcing properties of ethanol and not due to interference with satiety mechanisms, we compared the effect of two higher doses (10 and 20 mumol/kg, intraperitoneally, twice daily) of Goe 5438 on spontaneous preference for a non-caloric 0.04% saccharin solution in Sprague-Dawley rats. We observed a dose-dependent suppression of preference (by 44% and 58%, respectively) during the injection day, but not the subsequent 24 h period. However, Goe 5438 also significantly alleviated food pellet intake on the injection day. In conclusion, Goe 5438 produces potent and long-lasting inhibition of voluntary ethanol consumption, which may be secondary to attenuation of reinforcing properties of ethanol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615143 TI - Haloperidol reduces ethanol-induced motor activity stimulation but not conditioned place preference. AB - This experiment examined the impact of a dopamine receptor blocker on ethanol's rewarding effect in a place conditioning paradigm. DBA/2J mice received four pairings of a tactile stimulus with ethanol (2 g/kg, IP), haloperidol (0.1 mg/kg, IP)+ethanol, or haloperidol alone. A different stimulus was paired with saline. Ethanol produced increases in locomotor activity that were reduced by haloperidol. However, conditioned preference for the ethanol-paired stimulus was not affected by haloperidol. Haloperidol alone decreased locomotor activity during conditioning and produced a place aversion. These results indicate a dissociation of ethanol's activating and rewarding effects. Moreover, they suggest that ethanol's ability to induce conditioned place preference is mediated by nondopaminergic mechanisms. PMID- 1615144 TI - Opposite effects of pentylenetetrazol on self-defensive and submissive postures in the rat. AB - In a previous work, using the resident-intruder situation, we have shown that a benzodiazepine inverse agonist could exert a "fear-promoting" effect, in decreasing self-defensive behaviours while increasing submissive postures. To further test this hypothesis, the effects of pentylenetetrazol on different forms of defensive behaviour were examined in male intruder rats confronted with offensive residents. Administration of pentylenetetrazol (10 and 20 mg/kg, IP) increased submissive postures such as immobility and on-the-back, but reduced self-defensive postures. Other active behaviours were not reduced, thus excluding a non-specific behavioural suppression. These results suggest that self-defensive and submissive behaviours can be dissociated and that anxiogenic compounds are more likely to increase submissive behaviours than self-defensive ones. PMID- 1615145 TI - [Arcos system--rational procedures for optimization of conical crown adhesion]. PMID- 1615146 TI - [Individual baking procedure--system or accident?]. PMID- 1615147 TI - [Powder metallurgical preparation procedures of Degusint in dental laboratory and clinical application--an overview]. PMID- 1615148 TI - [Incorrect decisions in personnel management]. PMID- 1615149 TI - [Spiral block connection]. PMID- 1615150 TI - [10 year register. Volumes 21-30, 1981-1991]. PMID- 1615151 TI - [Frontier research on mesoderm induction in the early amphibian embryos]. PMID- 1615152 TI - [Pathophysiology of cerebral ischemia]. PMID- 1615153 TI - [Structure and activity of lipase]. PMID- 1615154 TI - [Ligament: a natural composite material to open the shells of bivalves]. PMID- 1615155 TI - [Dynamic fluorescence methods and their applications to biochemistry]. PMID- 1615157 TI - Sexual dysfunction. PMID- 1615156 TI - Sexual dysfunction in perspectives: an introduction. PMID- 1615158 TI - Sexual issues in the medically ill and aging. PMID- 1615159 TI - Prescription drugs and sexual function. PMID- 1615160 TI - The five-factor model of personality and sexual functioning in outpatient men and women. AB - 454 adults seeking evaluation at a sexual behaviors consultation clinic were evaluated for the major dimensions of personality as measured by the NEO Personality Inventory and various aspects of sexual attitudes and experiences via the Derogatis Sexual Functioning Inventory. The results showed that elevated Neuroticism was correlated with dysphoric symptoms, negative body image and lowered satisfaction. More extraverted individuals reported increased drive, more sexual experience, positive body image, and more positive affects. Agreeableness was unrelated to sexual drive and satisfaction but was negatively related to symptomatology. Openness was positively associated with amount of Information, range of sexual experiences, liberal attitudes toward sex, sexual drive and fantasy and appears to broadly impact upon sexual functioning. The more conscientious subjects had lowered sexual drive, but fewer dysphoric symptoms and a better body image. Women showed a similar pattern of personality correlates with the exception that personality was unrelated to females' sexual experiences and sexual satisfaction. The present findings support and expand previous research and contribute to our understanding of how personality dispositions influence the experience and expression of sexual functioning in male and female clinical samples. PMID- 1615161 TI - Normal aging and the evaluation of sexual dysfunction. PMID- 1615162 TI - Critique of the DSM-III-R nosology of sexual dysfunctions. PMID- 1615163 TI - Changes in terminology for sexual disorders in DSM-IV. PMID- 1615164 TI - Sexual and intimacy dysfunction among homosexual men and women. AB - Homosexually active men and women are no more immune than anyone else from various types of sexual dysfunction and underlying psychopathology. Intimacy fears and conflicts, ignorance, alcohol and drug dependence and relationship issues exemplify the type of issues influencing dysfunction regardless of sexual orientation, although membership of a stigmatized minority sexuality may exacerbate causes of sexual dysfunction. The effects of discordant lifestyle and identity, homosexual identity formation, dysphoria and internalized homophobia on sexual functioning are three examples of these factors of specific relevance to being homosexual in this culture. The effects of AIDS, difficulties arising from the mechanics of safer sex and the psychosexual effects of oppression on healthy sexual functioning all indicate how factors important to (but not caused by) minority sexuality status may influence sexuality functioning. The importance of neither perceiving homosexuality solely in terms of pathology on the one hand, nor refusing to recognize unhealthy sexual functioning on the other, is emphasized throughout. Models of sexuality must be inclusive, positive and communicated to the client if future sexual dysfunction is to be limited. Finally, the role of the therapist in community development, as well as individual intervention, is addressed. Primary health care interventions are required not only to address the specific issues affecting homosexual men and women, but also to promote a more positive approach to sexuality for all. PMID- 1615165 TI - Sexual aversion versus hypoactive sexual desire: a diagnostic challenge. AB - Our work with women with sexual aversion documents the presence of marked sexual avoidance behaviors as specified in the DSM-III-R1 diagnostic criteria for this disorder. At the same time, we demonstrate the presence of normal sexual desire and capacity for orgasm in these women. These two findings offer support for a valid diagnostic differentiation between sexual aversion disorder and hypoactive sexual desire disorder. Inherent in the diagnosis and treatment of sexual aversion disorder is an appreciation by the clinician of the tremendous approach avoidance conflict that exists in these patients. The behavioral and cognitive avoidance features, therefore, need to be elicited actively by the clinician during all phases of assessment and treatment. These features are not always offered readily by the patients for fear of having to relinquish these strategies and their related sense of control over the overwhelming anxiety that sexual intimacy can produce. Consequently, treatment is not always straightforward and successful. PMID- 1615166 TI - The early phase of treatment: an object relations approach. PMID- 1615167 TI - Does attention modulate the perception of luminance changes? AB - In a previous study assessing the modulation of visual processing by attention, Bonnel, Possami, and Schmitt showed that, when discriminating line-length, subjects precisely shared processing resources between two pairs of lines presented to the left and right of fixation. In a close replication requiring the detection of luminance increments instead of line-length differences, subjects were unable to follow the instructions and to allocate attention differentially, thus supporting the claim that light detection is fundamentally different from shape discrimination. In a subsequent experiment, we tested and rejected the possibility that luminance perception was not open to modulation by attention due to its physical nature. Replacing brightness detection by brightness identification allowed voluntary control on the quality of processing to be evidenced. The similarity between the latter results and the data from line length discrimination suggests that task requirements may be crucial in determining the distribution of attention. PMID- 1615168 TI - Privileged access by irrelevant speech to short-term memory: the role of changing state. AB - Memory for visually presented items is impaired by speech that is played as an irrelevant background. The paper presents the view that changing state of the auditory material is an important prerequisite for this disruption. Four experiments studied the effects of sounds varying in complexity in an attempt to establish which features of changing state in the auditory signal lead to diminished recall. Simple unvarying or repetitive speech sounds were not sufficient to induce the irrelevant speech effect (Experiment 1): in addition, simple analogues of speech, possessing regular or irregular envelopes and using a range of carriers, failed to imitate the action of speech (Experiment 2). Variability of between-utterance phonology in the irrelevant stream (Experiment 3) emerged as a crucial factor. Moreover, predictability of the syllable sequence did not reduce the degree of disruption (Experiment 4) suggesting that supra syllabic characteristics of the speech are of little importance. The results broadly support the idea that disruption of short-term memory only occurs when the speech stream changes in state. It is argued that disruption occurs in memory when cues to serial order based on phonological representations of heard material interfere with the phonological codes of visual origin. It is suggested that cues to changing state of the speech input contaminate those associated with items of visual origin, which are already in a phonological store. PMID- 1615169 TI - Towards an exemplar model of face processing: the effects of race and distinctiveness. AB - Valentine (1991a, 1991b) described a theoretical framework for face recognition in which faces are encoded as locations in a multidimensional space. It was argued that this approach could provide a unified account of the effects of distinctiveness, inversion, and race on face recognition. In this paper we evaluate the ability of this theoretical framework to account for the effects of distinctiveness and race in four experiments in which white British and Japanese faces served as stimuli and both white British and Japanese students acted as subjects. In a recognition memory experiment the expected "own-race bias" was observed as a Race of Subject x Race of Face interaction. Distinctive faces were recognized more accurately than typical faces, but the effect of distinctiveness did not interact with the race of face or the race of subject. Typical faces were classified faster than distinctive faces in a task in which intact faces had to be distinguished from jumbled faces, as found in earlier work, and the effect of distinctiveness did not interact with the race of face or race of subject. In contrast, a task in which subjects classified faces according to their race did show a greater effect of distinctiveness for own-race faces. The results are discussed in relation to the two specific models within the multidimensional space framework identified by Valentine (1991a): a purely exemplar-based model and a norm-based coding model. It is argued that these results are more easily accommodated in terms of a purely exemplar-based model. Some conceptual problems in applying the norm-based coding model to the effect of race are discussed. PMID- 1615170 TI - Against relative timing invariance in movement kinematics. AB - The kinematics of stair climbing were examined to test the assertion that relative timing is an invariant feature of human gait. Six male and four female subjects were video-recorded (at 60 Hz) while they climbed a flight of stairs 10 times at each of three speeds. Each gait cycle was divided into three segments by the maximum and minimum angular displacement of the left knee and left foot contact. Gentner's (1987) analysis methods were applied to the individual subject data to determine whether the duration of the segments remained a fixed proportion of gait cycle duration across changes in stair-climbing speed. A similar analysis was performed using knee velocity maxima to partition the gait cycle. Regardless of how the gait cycle was divided, relative timing was not found to remain strictly invariant across changes in speed. This conclusion is contrary to previous studies of relative timing that involved less conservative analysis but is consistent with the wider gait literature. Strict invariant relative timing may not be a fundamental feature of movement kinematics. PMID- 1615171 TI - The locus of repetition priming of spoken word production. AB - Naming of a pictured object is substantially facilitated when the name has recently been produced in response to a definition or read aloud. The first experiment shows this to be so when over one hundred trials have intervened, and when the subjects can name the pictures quickly and accurately in the absence of priming. The locus of the effect must be in lexicalization processes subsequent to picture identification and is unlikely to be mediated by recovery of an episodic trace. Two further experiments show that prior production of a homophone of the object's name is not an effective prime, (although slower responses are somewhat facilitated when the homophones are spelled the same). Hence the facilitation observed for repeated production of the same word cannot be associated with the repetition of the phonological form per se. We conclude that the facilitation must be associated with retrieval of the semantic specification or the process of mapping of that specification to its associated phonological representation. PMID- 1615172 TI - Repetition of lexicalization across languages: a further test of the locus of priming. AB - Wheeldon and Monsell (this issue) found that production of a word in response to a definition had a large and long-lasting facilitatory effect on latency for later production of the same word to name a pictured object, and that this priming effect was not due to repeated production of the phonological word-form per se. This paper reports a further test of the locus of the effect. Welsh English bilinguals named pictured objects in Welsh. Half the words were primed either by their earlier production in Welsh in response to Welsh definitions or by production of their equivalents in English in response to English definitions. Substantial facilitation resulted from prior production in the same language, none from prior production in the other language--provided that the equivalents differed in phonological form. Given that priming results neither from repeated activation of a meaning when different phonological forms are produced, nor from repetition of the same phonological form in response to different meanings, the priming effect must be localized in the connection between a word's meaning and its phonological form. We also put forward an account of bilingual lexicalization that accommodates this result together with some evidence indicating that production of words in one language is not wholly insulated from the "availability" of words in the other. PMID- 1615173 TI - Blood eosinophil count as risk factor for relapse in acute asthma. AB - In this retrospective investigation comprising 54 adult patients included in two studies of the treatment of acute asthma, the risk of relapse was studied. The set of variables that best predicted the length of time before a new asthmatic attack comprised blood eosinophil count (P less than 0.001), FEV1 on arrival (P less than 0.001) and increased medication on discharge (P less than 0.01). The set of variables that best predicted the number of new attacks during a period of 1 yr consisted of eosinophil count (P less than 0.001), FEV1 (P less than 0.001), increased medication on discharge, age and breathing rate on arrival (P less than 0.05). Patients with an eosinophil count of more than 500 x 10(6) l-1 and a FEV1 of less tha 1.0 l ran a six-fold greater risk of returning with a new attack within 1 month than patients with lower eosinophil count and higher FEV1. No significant correlation was found between post-treatment PEF variation and relapse in acute asthma. PMID- 1615174 TI - High dose nebulized steroid in the treatment of chronic steroid-dependent asthma. AB - Despite the dramatic success of inhaled steroids in controlling asthma symptoms there remains a small number of patients in whom asthma can only be treated with continuous oral steroids. Eighteen such patients, aged 19-62 years (seven males, 11 females) were followed in an open trial of nebulized budesonide over 12-18 months. All had required at least 7.5 mg or more daily prednisolone to control their symptoms over the preceeding 2 or more years and were taking 1200 micrograms beclomethasone dipropionate or 1600 micrograms budesonide daily. With a daily dose ranging between 4 and 8 mg nebulized budesonide, 14 patients successfully stopped oral steroids while in three the dose was reduced; only one patient failed to benefit. There was an increase in the mean FEV1 from 1.9 (+/- 0.9) to 2.2 (+/- 0.9) l, and in the mean morning PEFR, from 238 (+/- 119) to 286 (+/- 130) l min-1. There was also a significant decrease in the mean number of hospital admissions for acute severe asthma, from 1.5 (+/- 1.8) to 0.9 (+/- 1.1) per year. These findings should encourage a careful and controlled evaluation of nebulized steroids as a substitute for oral steroids in this difficult group of asthmatics. PMID- 1615175 TI - Humidification as an adjunct to chest physiotherapy in aiding tracheo-bronchial clearance in patients with bronchiectasis. AB - Humidification of inspired air or oxygen is frequently utilized by respiratory physiotherapists to relieve sputum retention. Cold water, jet nebulizing humidifiers are in widespread use but there has been no previous attempt to investigate the efficacy of this treatment. We have performed a single-blind, cross-over study to quantify the effect of humidification as an adjunct to chest physiotherapy. Seven patients with bronchiectasis completed the trial, with a mean (range) age of 51 years (41-64 years) and mean (range) percent of predicted FEV1 of 46% (29-76%). On 2 days, separated by 1 week, subjects were randomly allocated to humidification or no humidification as a precursor to an optimal chest physiotherapy regimen. A radio-aerosol of human serum albumin millimicrospheres labelled with 99mTechnetium was used to measure sputum clearance by serial gamma camera images. Serial measurements of sputum weight and FEV1 were also recorded. Humidification (30 min) was followed by postural drainage (20 min) with the subject using the forced expiration technique to assist clearance. When humidification was combined with physiotherapy there was a significant increase in total wet weight of sputum (P less than 0.05) with a median (range) increase of 6 g (-9-15.5 g); and a significant increase in total radiolabel clearance (P less than 0.05) with a median (range) increase of 8.7% (1 13%), compared to physiotherapy alone. This study demonstrates that the use of cold water, jet nebulizing humidifiers significantly increases tracheo-bronchial clearance above that of an optimal physiotherapy regimen alone in bronchiectasis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615176 TI - Predictors of mortality in silicosis. AB - The mortality of a cohort of 1487 male patients with silicosis in a population based register followed up from 1980 to 1986 was evaluated with reference to the mortality rates of the general male population. A striking excess of deaths from all causes (observed 368, standardized mortality ratio, SMR 3.00) was noted. Seventy-four percent of the deaths were due to respiratory conditions and complications directly or indirectly related to silicosis. The risk of death was especially higher than expected in younger patients under 45 years of age. Patients with simple silicosis of profusion category 1 did not appear to be at any increased risk of death relative to the general population, but increasing excesses of death were associated with greater extent of simple and conglomerate disease. These increased mortality risks were observed in tuberculosis-free patients as well as in those who never smoked. For the same extent of silicotic disease, the risk of death was higher if tuberculosis occurred. There was no evidence, however, that patients who smoked were more likely to suffer a worse mortality outcome than those who did not. Age at diagnosis, extent of silicotic disease and the occurrence of tuberculosis were therefore strong predictors of mortality in patients with silicosis. PMID- 1615177 TI - Inhaled steroids in patients with bronchiectasis. AB - The effect of inhaled beclomethasone diproprionate (1500 micrograms day-1) on symptoms, pulmonary function and sputum production was examined in a double blind, placebo-controlled, cross-over study in 20 patients with bronchiectasis. An 18% reduction in daily sputum production (P less than 0.003) was observed on treatment with inhaled steroid compared to placebo. A small, significant, improvement in morning peak expiratory flow rate (P less than 0.03) and forced expiratory volume in 1 s (P less than 0.03) was seen but the absolute changes are unlikely to be of clinical importance. Symptom scores for cough improved significantly (P less than 0.02). Inhaled steroids may have a role in the management of bronchiectasis by reducing cough and sputum production. PMID- 1615178 TI - The effect of high-frequency ventilation on non-Newtonian properties of bronchial mucus. AB - We have investigated the changes in the non-Newtonian properties of human bronchial mucus brought about by in vitro high frequency ventilation. This type of ventilation brought about changes in viscous properties, measured during creep and oscillation of the mucus, which would be expected to reduce mucus clearance in vivo. We suggest that any beneficial effects of clinical high-frequency ventilation on respiratory mucus clearance in patients are not brought about by long-term (more than a few seconds) changes in the viscous properties of the mucus itself. PMID- 1615179 TI - Inhaled sodium cromoglycate for pre-term children with respiratory symptoms at follow-up. AB - Children born prematurely frequently have recurrent respiratory symptoms at follow-up and benefit from bronchodilator therapy. We have assessed if regular inhaled sodium cromoglycate would reduce this respiratory morbidity and need for bronchodilator therapy. Sixteen symptomatic children (median gestational age 29 weeks, post-natal age 15 months) were entered into a randomized double-blind, placebo-controlled trial. In two 3-week periods, the patients received either placebo or sodium cromoglycate (5 mg) as one puff q.d.s. from an inhaler via a coffee cup. Parents recorded their child's symptoms and need for bronchodilator therapy throughout and lung function was assessed by measurement of functional residual capacity (FRC) at the beginning and end of each 3-week period. The symptom score was reduced by 49% in the active compared to the placebo period (P less than 0.01) and bronchodilator was taken on a mean of 2.9 days per infant in the active period compared to 7.9 days in the placebo period (P less than 0.01). There was a significant improvement in FRC in ten of 16 patients over the active period but only in two infants over the placebo period (P less than 0.01). We conclude regular inhaled sodium cromoglycate is useful prophylaxis for symptomatic pre-term children. PMID- 1615180 TI - Extrinsic allergic alveolitis: problems in diagnosis and a potential use for computed tomography. AB - Bird fancier's lung, the most common form of extrinsic allergic alveolitis in Britain, can be a difficult diagnostic problem. The symptoms are non-specific, often insidious in onset and frequently misdiagnosed as influenza or a viral or bacterial pneumonia. Frequently there is a delay in eliciting the history of exposure to the antigen. The chest radiograph is often less impressive than the clinical presentation and may be normal despite severe symptoms, impaired respiratory function and florid pathological changes. We present three cases demonstrating these diagnostic problem. In two cases, high resolution computed tomography demonstrated the typical 'ground glass' opacification seen in active alveolitis. This allowed targeting of transbronchial biopsies which revealed an inflammatory infiltrate of the interstitium with granuloma formation and inflammatory cells in some alveoli. The problems in diagnosis and the potential role of high resolution computed tomography are discussed. PMID- 1615181 TI - Persistent cough and sputum: prevalence and clinical characteristics in south east England. AB - In order to measure the prevalence of chronic respiratory symptoms in the population and to identify subjects for a case-referent study of aetiologic factors, 10,000 persons registered with general practices in south east England were surveyed. Responses to an initial postal questionnaire were validated by telephone interview; clinical interviews and simple spirometry were subsequently carried out on a sample of persons aged 5-54 years, reporting persistent sputum production. Results indicated that the postal questionnaire was an effective and sensitive method of surveying respiratory symptoms in the population. Comparison with earlier surveys suggests that the prevalence of chronic cough and sputum in Great Britain has fallen in males but not in females. Of those adults reporting persistent sputum production, high proportions reported associated symptoms of wheezing (54%), breathlessness (45%) or upper respiratory tract symptoms (54%). Thirty percent recalled a serious respiratory infection in childhood and 52% were current cigarette smokers although 34% reported that they had never been regular smokers. Overall there was little evidence of serious airflow obstruction in this group. PMID- 1615182 TI - Effect of bromhexeine on sputum amoxycillin levels in lower respiratory infections. AB - Bromhexeine has been widely used as an adjunct in the management of lower respiratory infections and is useful in altering the physical characteristics of sputum. Its effect on the sputum penetration of an antibiotic has been sparsely studied. The present study highlights the improvement in sputum amoxycillin (amoxy) levels when a combination tablet, amoxy 500 mg plus bromhexeine 8 mg, is administered as compared to plain amoxy 500 mg. Sputum amoxy levels were significantly higher in the combination group (0.674 +/- 0.588 micrograms ml-1) as compared to 0.272 +/- 0.19 micrograms ml-1 in the amoxy group (P = 0.028). The clinical responses assessed by the physician as well as the patient were significantly better in the amoxy plus bromhexeine group as compared to the amoxy group. The radiological and bacteriological responses were similar in both groups. There was no increase in the side-effects due to bromhexeine and, overall, its use can be recommended in the treatment of acute lower respiratory infections. PMID- 1615183 TI - Spontaneous arrest of growth of a plasma cell granuloma. PMID- 1615184 TI - 'Smoke-bomb' pneumonitis. PMID- 1615185 TI - A radiographer's asthma. PMID- 1615186 TI - Audit of tuberculosis contact tracing procedures in South Gwent. PMID- 1615187 TI - Epidemiological differences in pulmonary tuberculosis non-compliance and relapse. PMID- 1615188 TI - The value of routine microbial investigation in community-acquired pneumonia. PMID- 1615189 TI - N-acetylcysteine by metered dose inhaler in the treatment of chronic bronchitis: a multi-centre study. AB - Sixty-five patients with chronic bronchitis were studied at five different centres in a double-blind, randomized trial. Two parallel groups were treated with either N-acetylcysteine or placebo by metered dose inhalers for 16 weeks. Following a 1-week run-in period, each patient recorded subjective impressions of the drug action on their bronchitic symptoms in a diary once a week. In addition, exacerbations were registered. Lung function testing and adverse effects were evaluated by four visits to the chest clinics during the 16 weeks. We could not demonstrate that N-acetylcysteine by metered dose inhalers had any significant effect on patients' feeling of well-being, sensation of dyspnoea, intensity of coughing, mucus production, or expectoration or lung function. Its effect in reducing exacerbations could not be estimated because of a very low number of exacerbations reported. N-acetylcysteine inhalation was safe when used over a 16 week period. PMID- 1615190 TI - The effect of inhaled terbutaline on FEV1, FVC, dyspnoea and walking distance in patients with chronic obstructive lung disease. AB - This double-blind, placebo-controlled, crossover study was performed to evaluate the effect of terbutaline administered by a turbuhaler on spirometry, walking distance and dyspnoea during exercise in patients with chronic obstructive lung disease (COLD) and to evaluate relationships between changes in spirometry and working indices. The patients had a maximum reversibility in FEV1 of 15% predicted, and to ensure the option of studying correlations between changes in spirometry and working indices in patients with COLD a wide range of reversibility in FVC was ensured. Eighteen patients (M, 12; F, 6; mean age 68.5 years) were included in the trial. Mean baseline FEV1 was 0.921 and FVC 2.081. Six minutes unpaced walking distance on flat ground (WD) and Brog dyspnoea index scale (BS) were used as working indices. Baseline mean WD was 467.9 m, and median BS 3.2. No significant difference was found in the effect of terbutaline compared to placebo on the spirometry findings or WD. However, BS during exercise improved significantly on the terbutaline day. No significant correlation was found between changes in working indices and change in spirometry. Thus, the use of exercise testing and dyspnoea-scoring may reveal patients who benefit from acute bronchodilation without significant improvement in lung function. PMID- 1615191 TI - Neonatal respiratory support and lung function abnormalities at follow-up. AB - We have investigated if respiratory distress syndrome (RDS) treated by an increased inspired oxygen concentration, rather than mechanical ventilation, was associated with impaired lung function at follow-up and/or an increase in respiratory symptoms. Thoracic gas volume (TGV) and airways resistance (RAW) were measured in eight pre-term infants (median gestational age 29 weeks) at 6 and 12 months of age. The infants had suffered from RDS but had not required mechanical ventilation. Their results were compared to 16 other infants, matched for gestational age; eight who had required ventilation in the neonatal period and eight who had had no RDS. In all three groups the occurrence of respiratory symptoms was recorded. The lung function of the infants requiring oxygen in the neonatal period was similar to those who had not suffered from RDS, but their airways resistance was significantly lower at 6 but not 12 months than that of infants ventilated in the neonatal period (P less than 0.05). There was no significant difference in recurrent respiratory symptoms between the three groups although a greater proportion of the infants ventilated in the neonatal period were symptomatic in the first 6 months of life. These results suggest that oxygen therapy alone does not result in an impairment of lung function which is independent of the effect of prematurity. PMID- 1615192 TI - [Pneumologists against smoking]. PMID- 1615193 TI - [Primary malignant germinal tumors of the mediastinum]. PMID- 1615194 TI - [Primary malignant germinal tumors of the mediastinum. Results from a national retrospective survey]. AB - The object of this enquiry was to group together a series of patients with a mediastinal germ cell tumour who were diagnosed and treated between 1983-1990 to specify their clinical characters and their prognostic factors and to evaluate the current therapeutic strategies. Out of a total of 87 cases that were analysed 23 had seminomas and 64 malignant dysembryomas. Amongst the 23 patients suffering from seminomas, 8 had first been treated by surgery, 13 by chemotherapy and 2 by radiotherapy. At the end of treatment 22 made a complete response and 4 patients relapsed after 4-13 months following a complete response. 3 patients had metastases at the outset and were alive and in complete response at 1,4 and 7 years respectively. The survival level at 2 years for seminomas was 84%. Of 64 patients suffering from a malignant dysembryoma, 19 were first treated with surgery (10 by complete resection) followed by chemotherapy in 17 cases. At the end of treatment 12 patients were in complete remission. Only one of these patients had a subsequent relapse. 45 patients were first treated by chemotherapy (10 complete responses, 26 partial responses) then secondary surgery was performed in 22 cases, allowing a complete remission in 21. Seven malignant dysembryomas relapsed after an initial complete remission. The patients treated for pure choriocarcinoma were 7 in number: 6 of these received primary chemotherapy. One patient underwent a secondary resection and was living at 26 months. The other 5 died rapidly. The 2 year survival for malignant dysembryomas was 52%. The median survival was 28 months. There was a significant difference in surviyal between dysembryomas in complete remission and those in partial remission. PMID- 1615195 TI - [Mediastinal seminoma. Is it an entity to be treated differently?]. AB - The evolution of the therapeutic concepts of non seminomatous tumours (T) has chemotherapy as the preponderant treatment, and has also led to a different approach for mediastinal seminomas. In effect the traditional attitude for as complete an excision as possible followed by radiotherapy is in the process of changing. Certainly in 20% of cases a complete excision is possible. Post operative radiotherapy (30-50 grays) does not seem to change the survival and may be questioned in the management of invasive T. The radical debulking surgery of varying degrees no longer has a place. The standard treatment of inoperable T has remained for some time radiotherapy (35-40 grays). The survival at 5 years for these patients is around 60%, very close to the stage IIB seminoma of the testicles. If the seminoma seems to be radiosensitive it is also chemo-sensitive with an RC less than 80% in advance seminomas and of 90% in mediastinal seminomas. Thus there appears to be a contradictory debate; in the absence of precise staging of "thymic type" tumour and of randomised trials made difficult by the small number of cases one can envisage the following option: In the case of an inoperable T radiotherapy alone, excepting in the very bulky forms (diameter greater than 50% of the chest) or metastases where primary chemotherapy (CT) (4 cycles of VP16-platine) has a place: The treatment of the residual mass after CT depends on the size of the latter: less than 3 or equal to 3 cm by complementary treatment and greater than 3 cm by secondary surgery and if the seminoma is active complementary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615196 TI - [Germinal tumors of the mediastinum. Therapeutic strategy, prognosis, biology]. AB - Mediastinal germ cell tumors have a poor prognosis. Cisplatin containing chemotherapy combined with either primary or post-chemotherapy exeresis of the disease can induce a 50% cure rate. Acute leukemia is often associated with these tumors. In these cases, a clonal evolution from the germ cell tumor has been demonstrated. PMID- 1615197 TI - [Primary malignant germinal tumors of the mediastinum. Surgical aspects]. AB - Surgery retains an important place in the treatment of malignant germ cell tumours of the mediastinum though in order to achieve complete excision the appropriate moment for surgery needs to be chosen carefully. Complete excision, which is the great benefit of surgery, is rarely possible as first treatment because of the large volume of these tumours and their extension into mediastinal vascular structures. Considerable surgical experience is essential in order to allow extended incision involving the lung and the large vessels which might involve prosthetic replacements. Excepting in situations of great urgency surgery usually follows chemotherapy and is used as follows: in patients who appear to be in complete remission but who have residual lesions which require eradication, and those with malignant tissue which is persisting or more often of a mature teratoma which may have a risk of progressing. The return of tumour markers to normal values does not guarantee the absence of some residual cancer, in some patients with a partial remission complementary surgery may allow a further 20% to achieve a complete response, in the absence of a response to chemotherapy, surgical excision should be attempted without too long a delay and then followed by a different chemotherapy regime. PMID- 1615198 TI - [Plasma extravasation in the tracheo-bronchial airways. Mechanisms and physiopathological consequences in asthma]. AB - Plasma extravasation (EP) is an important phenomenon during the course of inflammation. In asthmatic subjects, EP is produced not only in the walls of the airways, but also in the lumen. This has consequences for the bronchial calibre and the qualitative and quantitative characteristics of the secretions. Numerous experimental methods have been developed in animals in order to study EP induced in the airways by different stimuli. For the most part these are inapplicable in man where EP is generally validated in an indirect fashion by measuring the quantity of certain plasma proteins, such as albumin in the secretions or the bronchoalveolar lavage. EP is linked to an increase in the permeability of the vessels, notably this is situated in the subepithelial zone. It is influenced by the appearance of disruption between the endothelial cells and possibly amplified by an increased blood flow linked to vasodilatation. It is the association of these phenomena of epithelial hyperpermeability which favours the appearance of EP in the lumen. In experimental systems the greater part of the mediators implicated in the pathophysiology of asthma are capable of inducing EP in the airways. The perfecting of reliable and non-invasive methods of study is, however, necessary to achieve a perfect understanding of the role of EP in the pathophysiology of asthma or other inflammatory diseases of the bronchi and to assess the efficacy of this parameter of different therapeutic techniques. PMID- 1615199 TI - [Inhaled corticosteroids in the treatment of childhood asthma]. AB - During the last fifteen years, inhaled corticosteroids were increasingly used for prophylaxis in childhood asthma. The development of inhaled corticosteroids with a high ratio of topical vs systemic potency, now makes possible their use in large doses which are needed to control the most severe forms of the disease, in order to avoid long term oral corticosteroid treatment for these patients. The efficacy of inhaled corticosteroids depends on an optimal pulmonary deposition of the drug which is obtained with children by inhaling the drug via a large volume spacer. Beyond their beneficial effects on the clinical condition of the patients and on pulmonary function, inhaled corticosteroids should improve the long term prognosis of asthma, by reducing chronic inflammation in the airways and the associated bronchial hyperreactivity. At usual dosages, inhaled corticosteroids are free of harmful side effects. However, caution and close observation of adrenal function and growth development are required when prescribing inhaled corticosteroids at high dosages for a long period. Nevertheless, inhaled corticosteroids present very few serious side effects compared with those induced by long term oral corticosteroid treatment. PMID- 1615201 TI - [Exercise tests in pneumology. C.R.E.D.O]. AB - Exercise tests have proved very useful in numerous areas such as sports medicine, research, clinical medicine and rehabilitation to exercise and therapeutic trials. It is not always easy for a pneumologist to decide what sort of effort and which protocol to use. There is also the question of which parameter to use and the relationship between parameters and which are the most pertinent as a function of the aim of the research. Above all the exercise test should be adaptable in view of the diversity of the objectives. In routine pneumology the exercise test using a bicycle ergometer and a triangular type of protocol are recommended for numerous reasons. The usual parameters (ventilation, oxygen consumption, production of carbonic dioxide, cardiac rate and blood gases) and their derivatives all have a value in the domain of cardiorespiratory physiology. It is important in clinical practice not to give too great an emphasis to the exact relationship expressed as a function of the workload, because the cycloergometer is practically never calibrated or even checked by the user. Dyspnoea was the major symptom leading the patient to seek a consultation and it is of primary importance that all effort tests include an estimation of the sensation of breathlessness. PMID- 1615200 TI - [Hyperventilation syndrome: current advances]. AB - The hyperventilation syndrome has been described for half a century but clearly remains underdiagnosed. Its acute manifestation is easily diagnosed ("the tip of the iceberg") but its recognition in numerous subtle forms requires a particular degree of alertness on the part of the clinician ("the hidden part of the iceberg"). The incidence of this syndrome in the general population varies according to different authors as between 6-11% and may mimic diverse organic disorders. The physiological consequences of hyperventilation are reviewed as well as their contribution in the clinical picture. The aetiology of the syndrome and its links with organic pathology or psychiatric disturbances continues to be debated. Is hyperventilation the expression of abnormal respiratory function or a preferred manifestation of anxiety? This article discusses and reviews the variety of tests which enable the presumptive diagnosis to be confirmed. The response to the proposed treatments is generally excellent when one takes account of the numerous possible options. These include comportmental therapies such as respiratory re-education, the utilisation of betablockers and psychotrophic drugs or psychotherapy. PMID- 1615202 TI - [Clinical characteristics and etiology in hemoptysis in a pneumology service. 291 cases]. AB - The aim of this work is to determine the clinical characteristics of haemoptysis and their principal aetiologies in a retrospective study of 291 cases collected over 5 years and occurring in adults who were hospitalised in a pneumology service. The annual incidence of haemoptysis was 8.8% of the in-patient population. The mean age of the patients was 46 and 47% were less than 50. The males were most frequent (69.4%) and haemoptysis was the presenting feature in 35.4%; it was minimal in 71.1% of average quantity in 26.8% and severe in 2.1%. The thoracic radiograph was judged abnormal in all cases and the abnormalities noted were suggestive of a particular aetiology in 70.8% of cases. The aetiological cause was dominated by bronchial cancer and of active pulmonary tuberculosis or its sequalae with levels of 34.4% and 18.9% respectively. For the other causes bronchial dilatation was important with 15.1% and hydatic cysts another 9.3%. Other aetiologies were represented by bacterial pneumonias with or without abscesses 7.2%, pulmonary aspergilloma 6.9%, chronic bronchitis with or without emphysema 3.5% and by rare causes in 4 cases. The cause for the haemoptysis was not found in 3.1%. This study brings out the preponderant place of bronchial cancer as a cause of haemoptysis in a country which still has a high prevalence of tuberculosis. Nevertheless the existence of tuberculosis services where the greater part of tuberculosis patients are hospitalised explains in part the predominance of bronchial cancer increasing very rapidly in our service. PMID- 1615203 TI - [Continuous oxygen therapy at home. Observations of oxygen users after an instruction program]. AB - The benefit of continuous domiciliary oxygen therapy (OCD) directly depends on the number of hours the oxygen is used daily. The observance of a correct regime is rarely met at present. For this reason we have done a prospective study for 24 months, assessing the compliance of 64 patients from 28 to 82 years of age. All these patients received a systematic and personal programme of education for 2 days in hospital. We subsequently measured, without the knowledge, either of the patient or the person caring from them, the quarterly oxygen usage. The mean duration of oxygen therapy was 14.7 +/- 3.6 hours. It remained stable during the 2 years of observation: 51% of the patients achieved a treatment of 15 hours or more and 10%, 10 hours or less. We did not find a significant correlation between the hours of compliance and the age, sex, FEV1, FVC and PaO2 or haemoglobin saturation. A significant statistical correlation with the PaCO2 was obtained. The more educated patients had better compliance levels than those of lesser education. The results obtained were better than those found in the literature at the present time. Perhaps it is explained by the level of education given. It cannot be excluded, however, that our severe criteria for the prescription of OCD has selected a population which was more susceptible to achieving good compliance. However, these results encourage the initiation of another prospective study using a control group to make a better assessment of the impact of education on the patient and his carers by the improved compliance in OCD. PMID- 1615204 TI - [Value of high resolution tomodensitometry in pulmonary histiocytosis X. Radiological, clinical and functional correlations]. AB - Histiocytosis is a rare cause of diffuse interstitial pneumonia. Its aetiology is not known and the outcome is often unsatisfactory. In 10 subjects in whom the diagnosis of histiocytosis X was established at CHU in Grenoble, 7 could be followed up. We report the clinical, functional, radiological and high resolution tomographic data on these 7 subjects suffering from histiocytosis X and followed up for a period between 3 and 13 years (8 +/- 3 years). All the subjects were symptomatic at the time of diagnosis. The clinical outcome amongst the 10 subjects included 2 patients who died, 2 who stabilised, 1 worsened and there were 4 clinical cures, 1 patient was lost to follow up. The respiratory function tests of the 7 subjects who were followed up was characterised by the appearance of airflow obstruction and a significant fall in the DLCO/VA (KCO) of 68 +/- 17% of the predicted value to 43 +/- 13%. An analysis comparing the initial pulmonary radiography to the current films showed that the reticular nodular lesions tended to progress to a diminution in size, while there was an increase in the reticulation. The high resolution computed tomography was confirmed as better technique than pulmonary radiography in detailing the cystic and nodular lesions. This was the only examination which correlated with DLCO/VA (R: 0.8; p: 0.018). A progressive model for computed tomographic lesions is proposed. Computed tomography appears to be the key examination, orientating the diagnosis based on the association of the nodules and cysts and enabling a better appreciation of the severity of the pulmonary disease taking account of its excellent correlation with diffusion. PMID- 1615205 TI - [Treatment of empyema and pyopneumothorax of infectious origin and chronic evolution by drainage-lavage with iodized polyvinylpyrrolidone]. AB - Thirty five patients, twenty nine men and six women with a mean age of twenty six and suffering from a pyothorax 23% or a pyopneumothorax 77% of whom 41% had a bronchopleural fistula on chronic evolution (greater than one month before drainage), had been treated using drainage and lavage with iodised polyvinylpyrrolidine without local or general antibiotics. This treatment enabled thirty four patients to be cured with some moderate radiological sequelae, a 50% restitution "ad integrum". The importance of the sequelae was correlated with increased aged (P less than 0.001), a delay before drainage (P less than 0.001) and a prolonged duration of drainage (P less than 0.01), to multiple organisms (P less than 0.01) and the presence of a pneumothorax (P less than 0.02) and to a tuberculous origin of the effusion (P less than 0.01). These two latter factors were the cause of a prolongation of the duration of drainage (P less than 0.01). Tuberculous patients who on average were older (P less than 0.05) and had a prolonged period of drainage (P less than 0.01) presented with major immediate radiological sequelae (P less than 0.01). In conclusion the technique of drainage using iodised polyvinylpyrrolidine gave excellent results in cases of non tuberculous pyothorax in young subjects, but gave less impressive results in subjects suffering from tuberculosis, because of the significant radiological sequelae. PMID- 1615206 TI - [Use of intravenous adrenalin in severe acute asthma]. AB - The efficacy of and tolerance to intravenous Adrenaline (IV) have been assessed in cases of acute severe asthma (AAG). From January 1983 to March 1990 there were 56 episodes of AAG treated by intravenous Adrenaline using an average dose of 0.33 microgram per kilogramme per minute, in association with intravenous steroid therapy and Aminophylline (0.6 mg/kg per hour). A group of 12 patients were ventilated before admission and were excluded from the study. Two groups were defined on the basis of their admission PaCO2: Group A with 30 episodes of AAG and a PaCO2 above 45 mm of mercury, Group B with 14 episodes of AAG and a PaCO2 of less than 45 mm of mercury. The clinical improvement was equally rapid in both groups on average 8.7 (plus or minus 8.2) hours in Group A and 14.6 (plus or minus 15.7) hours in Group B. Artificial ventilation was only required in 2.3% of cases (7% in Group A and none in Group B). Treatment using intravenous Adrenaline is well tolerated as is shown by the absence of any worsening of the tachycardia, the significant fall in blood pressure after correcting the PaCO2 in Group A and the absence of any raised blood pressure in Group B. In conclusion, treatment with intravenous Adrenaline associated with IV Theophylline and IV corticosteroids based on the fact of its rapid action and that it is well tolerated, means that this drug should be considered as part of the therapeutic arsenal during acute severe asthmatic attacks in patients who are breathing spontaneously. PMID- 1615207 TI - [Follicular bronchiolitis: a pediatric case report]. AB - A case of bronchiolitis of insidious evolution appearing in an unweened infant aged six months is reported. Initially an acute episode of bronchial obstruction was followed by respiratory failure with failure to thrive. The total inefficacy of conventional treatment (corticosteroids, nebulised and oral bronchodilators) led to assisted ventilation for three weeks, four months after the onset of symptoms. All investigations aimed at achieving a diagnosis were negative and this led to an open lung biopsy. This showed characteristic lesions of bronchiolitis and follicular bronchitis without other parenchymatous disease. With continuous antibiotics and physiotherapy the respiratory status improved, both clinically and radiologically. Amongst the explanations of the pathophysiology of follicular bronchitis they also discussed the existence of heterozygous delta F 508 in their observation to explain the chronicity of the problems. They stress the need to look for a mutation of delta F 508 in infants who present with unexplained obstructive bronchial pathology. PMID- 1615208 TI - [A case of congenital pulmonary varices]. AB - Pulmonary varices are rare disorders (only 72 published cases), and are most often congenital in origin, asymptomatic and have a benign outcome. In some cases the appearance of varices is favoured by pulmonary venous hypertension which is most often related to mitral valve disease, or it is associated with other vascular or bronchial malformations. We present a new case of isolated pulmonary varices occurring in an asymptomatic young woman aged 20. The pulmonary radiological abnormality was confirmed using computed tomography which showed that the abnormality was both of vascular origin and of venous composition. Digital subtraction angiography during the venous phased confirmed the diagnosis. There was no associated cardiomyopathy, nor any bronchial or vascular malformation. No surgical intervention was taken, nor was there any clinical or radiological change observed during follow-up over one year. The diagnosis of pulmonary varices is an important one to make, particularly to avoid an unnecessary thoracotomy, but there should always be a systemic search for associated anomalies. PMID- 1615209 TI - [Diagnosis of an unusual thoracic opacity]. PMID- 1615210 TI - [A dyspnea of unusual cause in a chronic bronchitis patient]. PMID- 1615212 TI - [Pneumology Society of French Language. List of members 1992]. PMID- 1615211 TI - [A historical case of disseminated tuberculosis]. PMID- 1615213 TI - Peptides in oncology I. LH-RH agonists and antagonists. PMID- 1615214 TI - Gonadotropin-releasing hormone: physiological and endocrinological aspects. PMID- 1615215 TI - LH-RH antagonists: state of the art and future perspectives. PMID- 1615216 TI - Treatment of uterine leiomyomata by LH-RH agonists. PMID- 1615217 TI - On the management of metastatic prostate cancer with LH-RH analogs. PMID- 1615218 TI - Combination therapy with flutamide and castration (orchiectomy or LH-RH agonist) in untreated patients with advanced prostate cancer. PMID- 1615220 TI - Treatment of endometrial cancer with GnRH analogs. AB - Given the small number of side effects, GnRH may be a useful and ideal drug for new therapeutic hormonal approaches in many cases of both invasive and noninvasive endometrial cancer. The hypoestrogenic state thus induced as well as a local effect may lead to pronounced regression of the tumor. Any future therapy should, however, always be tailored to meet individual needs. The use of GnRH agonists may be advocated in the following circumstances: 1. In pronounced endometrial hyperplasia and adenomatous hyperplasia (particularly relevant in those cases where hysterectomy is not desirable, e.g., in young patients who have not yet completed their families). 2. In patients with endometrial cancer where surgery is contraindicated or refused. 3. In addition to or as a substitute for radium treatment preoperatively to reduce uterine volume (myomas) to make surgery technically easier; to devitalize the tumor, stop menorrhagia, and improve anemia. 4. In advanced cases as an adjunct to radiotherapy and gestagens. It is possible that this will produce synergistic effects. 5. As adjuvant treatment (replacing gestagens?) in primary stages. 6. In relapses of endometrial cancer, refractory to conventional therapy, and in pulmonary metastases. PMID- 1615219 TI - LH-RH agonists in the treatment of ovarian cancer. PMID- 1615221 TI - Direct antitumor effects of LH-RH analogs. PMID- 1615222 TI - LH-RH agonists in the treatment of metastatic breast cancer: ten years' experience. PMID- 1615223 TI - LH-RH agonists in the treatment of premenopausal patients with advanced breast cancer. PMID- 1615224 TI - Modelling steady state pulmonary elimination of He, SF6 and CO2: effect of morphometry. AB - We studied the influence of acinar morphometry on the shape of simulated expirograms computed from a single path convection-diffusion model that includes a source term for gas evolution from the blood (Scherer et al., J. Appl. Physiol. 64: 1022-1029, 1988). Acinar structure was obtained from published data of 3 different lung morphometries. The simulations were performed over a range of tidal volumes (VT) and breathing frequencies (f) comparable to those observed in a previously reported human study. Airways dead space (VDaw) increased with VT in all the morphometric models tested and in the experimental data. The increase in VDaw with VT was inversely related to the diffusivity of the evolving gas and to the rate of increase in airway cross-section of the most mouthward (proximal) alveolated generations of the models. Normalized phase III slope for all the gases decreased with increasing VT in all the models as was previously reported for healthy human subjects. In the model simulations, the greatest sensitivity of phase III slope to VT was seen with the least diffusible gas using the airway morphometry with the smallest cross-sectional areas in the proximal alveolated generations. We conclude that both VDaw and phase III slope of an evolving gas are sensitive to the geometry of the proximal acinar airways and that this is manifest by their dependence on tidal volume, breathing frequency, molecular diffusivity and alveolar/blood source emission rate. The model simulations indicate that heterogeneity of gas washout is not required to explain the magnitude of the phase III slope in healthy human subjects. PMID- 1615225 TI - The effect of vagal stimulation on the distribution of inspired gas in the lungs. AB - We investigated the direct effects of efferent vagal activity on the distribution of inspired gas by stimulating the vagus nerve of one lung and measuring the topographic distribution of a radioactive tracer (133Xe) to both lungs. The distribution of inspired (133Xe) boli was measured with NaI scintillation detectors placed apex-base over each posterior lung of intubated, paralyzed, anesthetized dogs. In 7 supine dogs vagal stimulation reduced the distribution of rapidly insufflated 133Xe boli (flow greater than 2.5 L/s) to the test lung (P less than 0.02), but not when boli were insufflated slowly (flow less than 0.5 L/s), suggesting that vagal stimulation affects pulmonary gas distribution primarily by increasing airway resistance and not through changes in lung compliance. The effect of vagal stimulation on the regional apex-base distribution of inspired gas (greater than 2.5 L/s) was measured in 7 supine and 5 upright dogs. In the supine position, vagal stimulation did not change the uniform apex-base bolus distribution, whereas in the upright position less of the bolus was distributed to the middle and lower lung regions (P less than 0.043), compared to control measurements. This indicates that the regional effects of vagal stimulation on the distribution of inspired gas are uniform in the supine position, but that vagal stimulation alters the distribution of inspired gas when the apex-base pleural pressure gradient is increased. PMID- 1615226 TI - Spike trains from single motor units in human parasternal intercostal muscles. AB - Recordings of single motor unit activity were obtained from parasternal intercostal muscles of normal humans during quiet breathing. Spike trains from 52 individual motor units were analyzed. All these units were low threshold ones, recruited at low inspired volumes and therefore at low tension thresholds. Mean frequency of firing at onset was 7.8 Hz and mean increase in frequency through the breath was 3.6 Hz. Onset and peak frequencies were positively correlated with inspiratory flow rate. Alternation of interspike intervals between long and short was found in the spike trains of 6 of 13 units tested and this occurred at frequencies of 6-12/s. Doublet discharges at the beginnings of spike trains were seen during voluntary neck flexion but never in quiet breathing or voluntary deep breaths. The pattern of activity in these human intercostal motor units was similar to that reported for low threshold, slow twitch units in other mammalian skeletal muscles, including respiratory muscles. PMID- 1615227 TI - Effects of different levels of end-tidal PO2 on ventilation during isocapnia in humans. AB - The purpose of this investigation was to examine how the ventilatory decline observed during sustained, eucapnic hypoxia (HVD) is affected by different levels of hypoxia. Six subjects were each studied 3-6 times at each of 5 different levels of isocapnic hypoxia (end-tidal PO2 equal to 45, 50, 55, 65 and 75 Torr) in random order. The following variables were linearly related to saturation: (1) the rapid increase in ventilation at the onset of hypoxia; (2) the decline in ventilation over the period of hypoxia; and (3) the undershoot in ventilation below the pre-hypoxic control values at the relief of hypoxia. The rapid decrease in ventilation at the relief of hypoxia, however, was not linearly related to saturation. The mean time to peak ventilation was 2.13 +/- 0.07 min (+/- SE) at the onset of hypoxia, which was significantly longer (P less than 0.05) than the time to minimum ventilation at the relief of hypoxia of 1.23 +/- 0.18 min. The recovery from the undershoot in ventilation was 95% +/- 3% complete after 5 min, whereas the recovery in sensitivity to hypoxia was only 35% +/- 13% complete after 5 min of euoxia. PMID- 1615228 TI - The chaotic behaviour of resting human respiration. AB - The study of non-linear mathematics has led to the concept of an attractor that can confine to within certain boundaries the path traced out in multidimensional space when a variable is plotted against itself delayed by various lag times. The type of attractor present can be determined by monitoring the exponential rate (called a Lyapunov exponent) at which almost identical values within a time series become dissimilar. Lyapunov exponents estimated from data collected during the normal resting breathing of eight adults were all positive, end-tidal PCO2 had the lowest Lyapunov exponent (0.06 +/- 0.01 bits/s; Mean +/- SE), breath and expiratory duration had the highest exponents (0.23 bits/s). The results indicate that resting respiration is chaotic. This chaotic behaviour may allow fast and flexible responses to sudden changes, allow if necessary complete readjustment of the control parameters, and may be involved in the phase locking of respiration to external stimuli. PMID- 1615229 TI - Properties of postganglionic sympathetic neurons with axons in phrenic nerve. AB - The aim of the study was to test the reflex and resting properties of postganglionic sympathetic neurons with axons located in the right phrenic nerve. The experiments have been performed on chloralose-anesthetized cats with both vago-aortic nerves cut. The somata or the postganglionic sympathetic neurons were located in the stellate ganglion. Axons of these neurons passed through the upper and lower phrenic nerve roots and through the phrenic nerve itself. The presence of cardiac and respiratory rhythmicities was detected in the activity of the phrenic postganglionic sympathetic neurons. Hyperventilation, which abolished burst discharges of the phrenic nerve, decreased the sympathetic activity by 14%. Systemic hypoxia (ventilating the animals for 2 min with 8% O2 in N2) increased the sympathetic activity threefold. The results of our experiments suggest that axons of the sympathetic neurons located in the right phrenic nerve could possibly be diaphragmatic muscle vasoconstrictors. PMID- 1615230 TI - The effect of blood flow and left atrial pressure on the DLCO in lambs and sheep. AB - Previous studies suggest that pulmonary capillary distensibility and recruitment may differ in lambs and sheep. To study the effect of pulmonary blood flow (PBF) and vascular pressure on capillary hemodynamics in lambs and sheep we measured the diffusing capacity for carbon monoxide (DLCO) as an index of pulmonary capillary blood volume during a baseline period, after increasing PBF, and during left atrial hypertension. In the lamb, DLCO did not change significantly either with a 65% increase in PBF or with an increase in left atrial pressure (Pla) of 1.33 kPa at constant PBF. In the sheep on the other hand, doubling PBF led to a 28% increase in DLCO (P less than 0.02), and an increase in Pla of 1.87 kPa at constant PBF led to a 19% increase in DLCO (P less than 0.01). These results suggest that the neonatal lamb has a nearly fully recruited and relatively non compliant pulmonary capillary bed at rest, unlike the adult sheep which can respond to hemodynamic changes with distension and recruitment of the pulmonary capillary bed. PMID- 1615231 TI - Effects of muscle temperature on the VO2 kinetics at the onset of exercise in man. AB - The kinetics (i.e. the rate of readjustment) of O2 uptake (VO2) at the mouth of muscle blood flow in the vastus lateralis muscle (Qm), and the net accumulation of lactate in the rest-to-exercise transient (early lactate) were assessed in 6 untrained men (age 31 +/- 8 (SD) yrs) during constant-load 5-min duration exercises on the cyclo ergometer of 75 and 125 W, performed at muscle temperatures (Tm) of 35.5 +/- 0.9 degrees C (N) and of 28.0 +/- 1.65 degrees C (C). VO2 was measured breath-by-breath; Qm was assessed from 133Xe clearance; early lactate was calculated as the difference between the venous lactate concentrations observed after and before exercise. At both work loads, steady state VO2 was slightly higher in N than in C (P less than 0.05 at 75 W; NS at 125 W). The half-times of VO2 kinetics were: in N, 36.2 +/- 6.7 s at 75 W and 41.6 +/ 8.6 s at 125 W; in C, 41.4 +/- 10.0 at 75 W and 43.8 +/- 14.0 at 125 W (NS). Mean steady state Qm was 8.5 ml.min-1.100 g-1 in C, and 13.4 in N at 75 W (NS); at 125 W, Qm was 18.3 ml.min-1.100 g-1 in C vs. 25.0 in N (NS). The half-times of the Qm kinetics tended to be slower in C than in N (NS). At both work loads, early lactate was slightly greater in C than in N (NS). It is concluded that, at submaximal exercise, (a) steady state VO2 and the VO2 kinetics are not affected by Tm, and (b) at the onset of exercise Qm does not affect VO2 kinetics. PMID- 1615232 TI - Acclimatization to hypoxia alters cerebral convective and diffusive O2 delivery. AB - Ventilatory acclimatization (VA) to hypoxia alters cerebrovascular responses to arterial blood gas perturbations. For example, after VA, cerebral blood flow (CBF) is elevated, at a given arterial CO2 tension (PaCO2), compared to CBF before VA. This experiment examined the effects of VA to 72 h of normobaric hypoxia [arterial O2 tension (PaO2) approx. 40 mmHg, O2 saturation in arterial blood approx. 50%] on total and regional cerebrovascular resistance (CVR and rCVR) and cerebral O2 extraction fraction (OEF) in 32 conscious sheep. Four different O2-CO2 gas combinations were sequentially administered to each sheep before and after VA. CVR and rCVR were calculated from CBF (radiolabeled microspheres) and arterial and cerebral downstream pressures; OEF was calculated from arterial and cerebral venous O2 contents. After VA, during hyperoxia, CVR and rCVR tended to be lower during both hypocapnia and hypercapnia. During hypoxia, although CVR and rCVR were slightly less during hypocapnia, CVR and rCVR during hypercapnia were surprisingly increased. The post-VA increases in mean CVR and mean rCVR during hypoxic gas combinations differed from the post-VA decreases during hyperoxic gas combinations (0.04 less than or equal to P less than or equal to 0.11). In contrast, although VA decreased OEF during three of four gas combinations (P less than or equal to 0.003), there was a greater mean post-VA decrease in OEF during hypercapnic gas combinations than during hypocapnic gas combinations (P = 0.025); decreases in OEF were correlated with decreases in cerebral O2 consumption. The post-VA CVR responses may reflect altered neurocirculatory control by the arterial chemoreflex; the OEF responses suggest relative cerebral hyperperfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615233 TI - Cardiovascular responses to hypoxia in the hagfish, Eptatretus cirrhatus. AB - Simultaneous measurements of cardiac output (Q), blood pressures and blood gases were made in the hagfish, Eptatretus cirrhatus, during exposure to hypoxia. The partial pressure of oxygen in the medium (PIO2) was reduced from 20.7 kPa to 8.0 kPa and then lowered to 5.3 kPa. At a PIO2 of 5.3 kPa there was a 40% increase in Q. Part of the increase may have been due to the increased activity of the animal at low PIO2. In recovery, when the animals were inactive, Q continued to rise to 160% of the control values. At 5.3 kPa, oxygen consumption (as determined by the Fick principle) fell to 29% of the normoxic value and was associated with increased branchial vascular resistance (Rg) and an increased diffusion limitation of the gills (Ldiff). Adrenaline increased heart rate and aortic blood pressures. Increased Rg and Ldiff could be provoked in normoxia by the injection of the beta-adrenergic blocking drug propranolol. We suggest that catecholamines may be involved in the tonic control of gill vasomotor tone. PMID- 1615234 TI - The human immunodeficiency virus, type 1: the virus and its role in neurologic disease. PMID- 1615235 TI - Epidemiology of human immunodeficiency virus infection and the neurologic complications of the infection. PMID- 1615236 TI - Human immunodeficiency virus-related cognitive impairment and the acquired immunodeficiency syndrome dementia complex. PMID- 1615237 TI - Management of neurologic opportunistic disorders in human immunodeficiency virus infection. PMID- 1615238 TI - Neuromuscular complications of human immunodeficiency virus infection. AB - As the lifespan of patients with HIV infection is prolonged with more effective antiviral therapies, the prevalence of neuromuscular disorders is likely to increase. The understanding of the pathogenesis and optimal therapy of these illnesses has advanced during the past 5 years. However, there are still significant gaps in our knowledge. It is important that neurologists remain at the forefront of investigation and treatment of these complex disorders. PMID- 1615239 TI - Syphilis and human immunodeficiency virus infection. PMID- 1615240 TI - Neurologic manifestations of pediatric acquired immunodeficiency syndrome: clinical features and therapeutic approaches. PMID- 1615241 TI - Brain imaging in human immunodeficiency virus infection. PMID- 1615242 TI - "A common geography of the mind": physicians in AIDS literature. PMID- 1615243 TI - Doctor vector. PMID- 1615244 TI - Pretransplant evaluation and outcome. PMID- 1615245 TI - Need, demand, and supply in kidney transplantation: a review of the data, an examination of the issues, and projections through the year 2000. PMID- 1615246 TI - Pancreas transplantation. PMID- 1615247 TI - Trends and concepts in the prescription and delivery of dialysis in the United States. PMID- 1615248 TI - Commonly measured laboratory variables in hemodialysis patients: relationships among them and to death risk. PMID- 1615249 TI - Comparison of treatment costs between dialysis and transplantation. PMID- 1615250 TI - Extrarenal manifestations of autosomal dominant polycystic kidney disease. PMID- 1615251 TI - Fluid replacement during exercise in the heat. Review and recommendations. PMID- 1615252 TI - Physiological adaptations to velocity-controlled resistance training. AB - The force-velocity characteristics of skeletal muscle are such that maximal force is inversely related to the velocity of shortening. This relationship has been observed using isolated muscle preparations and intact muscle groups (e.g. knee extensors). Isokinetic dynamometry has revealed some specific physiological adaptations to different velocities of training: an increase in torque and power that are greater at or near the velocity of training; a transfer of torque gains to slower and faster angular velocities after intermediate velocity resistance training; increases in maximal oxygen consumption and cardiac output in response to circuit training; increases in anaerobic power output; changes in skeletal muscle size and changes in myofibrillar ATPase activity; and new applications for rehabilitation of muscular and ligamentous injuries, and post-coronary patients. PMID- 1615254 TI - Softball injuries. Aetiology and prevention. AB - Over 40 million individuals nationally participate in organised softball leagues, playing an estimated 23 million games per year in the United States. It has also been estimated that softball causes more injuries leading to emergency room visits in the United States than any other sport. Between 1983 and 1989, over 2.6 million injuries were documented through selected emergency rooms throughout the United States. In addition, the potential costs of these injuries can be staggering, therefore, prevention is of utmost importance. Prior to implementation of any preventative measures, the aetiology and distribution of injuries must be ascertained. Softball-related injuries can be grouped into 3 categories: (a) sliding-related injuries--the most common injury scenario; (b) collision-related injuries; and (c) falls sustained by the player. Various preventative approaches have been utilised to reduce the incidence of these recreational sports injuries and the associated health care costs. In regard to sliding-related injuries, breakaway bases have been utilised and have been found to reduce sliding-related injuries by approximately 98%. In reference to collision injuries, deformable walls and padded back stops and field maintenance have been found to prevent the majority of injuries secondary to collisions and falls. In addition, better coaching techniques as well as stretching and conditioning programmes have all been found to benefit players in the prevention of their injuries. As physicians, trainers and individuals involved with sporting activities, it is imperative that we turn and focus our attention on prevention. The cornerstone to diminished injuries and subsequent prevention of an injury is a safer environment for the recreational softball player to participate in. PMID- 1615255 TI - Return-to-work evaluation after coronary events. Special emphasis on simulated work activity. PMID- 1615253 TI - Body fat assessment in women. Special considerations. AB - Methods of in vivo body fat estimation are based on simple assumptions about body composition which work reasonably well for men, while estimations in women have been largely extrapolated from the male studies so that women are treated as men with just more of the same fat. Compared to men, fat regulation in women is considerably more elaborate, with more and different sites for storage and a larger proportion of fat distributed to the extremities and in subcutaneous locations. Thus, a ratio of waist-to-hips girth which reflects increasing fatness in men only specifies 2 different extremes of a broader spectrum of possibilities for fat distribution in women. This complicates anthropometric prediction of total fatness and clearly limits the generalisability of any female equations. Anthropometric methods are further confounded by difficulties in the criterion methods against which they are developed. For example, the validity of assumptions about the fractional contributions of bone mineral and body water to fat-free mass and density may not hold through the reproductive cycles. Women athletes involved in weight-bearing or strength training may increase bone mineral content above average values but if they become amenorrhoeic, bone mineral density may fall significantly below average values. Fit premenopausal women distribute fat differently and have a higher bone mineral content than unfit postmenopausal women. Genetic factors which also affect criterion method assumptions in men are superimposed on these additional complications in women. Body fat in female athletes extends across almost the entire range of female fatness, with some of the lowest measurements in distance runners and body builders which fall into the normal male range, but also with some relatively high values in swimmers and strength athletes, which would classify these women as obese by male standards. Thus, total body fat reflects a more complex regulation and has a different meaning to health and performance in women than it does for men. Predictive equations for women athletes should be developed with a view to the specific group and ultimate purpose to which they will be applied. PMID- 1615256 TI - Biomechanics of sprint running. A review. AB - Understanding of biomechanical factors in sprint running is useful because of their critical value to performance. Some variables measured in distance running are also important in sprint running. Significant factors include: reaction time, technique, electromyographic (EMG) activity, force production, neural factors and muscle structure. Although various methodologies have been used, results are clear and conclusions can be made. The reaction time of good athletes is short, but it does not correlate with performance levels. Sprint technique has been well analysed during acceleration, constant velocity and deceleration of the velocity curve. At the beginning of the sprint run, it is important to produce great force/power and generate high velocity in the block and acceleration phases. During the constant-speed phase, the events immediately before and during the braking phase are important in increasing explosive force/power and efficiency of movement in the propulsion phase. There are no research results available regarding force production in the sprint-deceleration phase. The EMG activity pattern of the main sprint muscles is described in the literature, but there is a need for research with highly skilled sprinters to better understand the simultaneous operation of many muscles. Skeletal muscle fibre characteristics are related to the selection of talent and the training-induced effects in sprint running. Efficient sprint running requires an optimal combination between the examined biomechanical variables and external factors such as footwear, ground and air resistance. Further research work is needed especially in the area of nervous system, muscles and force and power production during sprint running. Combining these with the measurements of sprinting economy and efficiency more knowledge can be achieved in the near future. PMID- 1615258 TI - Factors related to the incidence of running injuries. A review. AB - The term incidence is interpreted in many different ways in the literature. Running injury epidemiology should include denominator-based incidence rates, in which the number of new injuries observed during 1 year is related to the population of runners at risk. In 10 studies with denominator-based incidences selected from the literature, the annual incidence rates of injured runners vary from 24 to 65%. Comparison of denominator-based incidence rates from different studies requires a discussion of the denominator and of the numerator; i.e. the study population and the definition of running injury. Injury definitions differ from one study to another. Study populations are particular subgroups of the total running population and they differ from one study to another. Subgroups may differ in origin: volunteers, runners from a mailing list or entrants of a road race. Incidence rates are higher among supervised volunteers than among listed runners, and higher among both these groups than among race-entrants. The choice from the universe of the running population and the used injury definition are methodological issues. Incidence is dependently associated with the prevalence of predisposing running injury factors. There is consistent epidemiological support for the role of a few aetiological factors; i.e. higher mileage per week, previous running injury, higher running speed and lesser running experience. Higher mileage per week is probably the strongest predictor. In the selected injury studies, mileage per week differs from one study population to another. Differences in mileage per week do not explain differences in incidence rate between these studies. In conclusion, caution must be taken when comparing annual incidence rates of different studies. Methodological issues are at least as important as aetiological factors. Study populations may refer to different selections of the universe of the running population. The lengths of observation periods and 'running injury' definitions may differ from one study to another. PMID- 1615259 TI - Meniscal injury in the anterior cruciate-deficient knee. A rationale for clinical decision-making. AB - Meniscal injury is common in acute or chronic anterior cruciate ligament insufficiency. The patterns of meniscal lesions are predictable in the acute and chronically unstable knee. The early incidence of meniscal injury is high and increases with time. Meniscal repair has become increasingly successful. Techniques for anterior cruciate ligament reconstruction have also improved, and with more progressive rehabilitation programmes, this has become a more tolerable procedure for both patients of highly athletic lifestyles and more moderate recreational athletes. The decision-making process for the sports medicine physician requires an overall assessment of many variables. A delicate balance of factors such as age, sex, joint laxity, activity level, individual motivation, social circumstances, associated meniscal, collateral ligament and/or chondral damage may sway the surgeon towards a nonoperative or operative decision. At the present time, a 'cook book' answer to each case presented is not available. As in all of medicine, each patient is an entity that requires an individual evaluation and a specific course of treatment. This review aims to help in this decision making process. Future prospective studies investigating the many variables mentioned will hopefully objectively delineate guidelines for the choice of the most effective therapeutic regimen. PMID- 1615260 TI - Tumor registrar's role in TNM staging. AB - The role of the tumor registrar in TNM staging has not been clearly defined. This paper shows how this can be clarified in individual hospital cancer programs and how the tumor registrar serves as a key member of the cancer team in implementing physician TNM staging. PMID- 1615257 TI - Effects of physical activity on some components of the skeletal system. AB - Sporting activities impose on the skeletal system forces of a high intensity and frequency. Ligaments, bone and tendons behave in a time-dependent load-extension fashion, and it is important for both scientists and clinicians to consider, for example, the alterations in failure properties shown by ligaments, tendons and bone at different rates of deformation. Whether the ability of the skeletal system to withstand stress can be improved with appropriate training is still controversial. The effects of physical exercise depend on the modality, intensity and duration with which the exercise itself is performed. Moreover, genetic factors, also influencing growth and hormonal status, may exert a significant influence on the response of a given tissue to an external load. Overloading may cause a lesion, and this may decrease or annihilate performance capability. The skeletal system may not be resistant enough, and so it may prove limiting to intensive physical activity. In vitro studies on resistance of a single tissue have not taken into consideration the specific resistance of that structure in vivo, and the results so obtained cannot be readily extrapolated to sporting activities, as in vivo muscles, joints, tendons, ligaments and cartilage act as one. This article reviews some of the possible beneficial and detrimental effects of intense exercise on various components of the skeletal system, focusing on its ability to withstand and adapt to stresses and allow maximal performance. PMID- 1615262 TI - Cancer staging. PMID- 1615261 TI - Cancer staging: future directions for the TNM classification. AB - The major accomplishment of the 1987 edition of the TNM classification was the unification of criteria for all site classifications, namely, the elimination of all variations that had developed over the years. The main directions that TNM is taking for the future are 1) verification of published classifications, 2) classification of new sites and tumor types, 3) addressing the integration of nonanatomic factors with TNM to achieve prognostic grading, and 4) application of TNM beyond pure clinical-pathological aspects to assess methods of early detection, quality of care, and population trends. PMID- 1615263 TI - Cancer staging. PMID- 1615264 TI - Survival results depend on the staging system. AB - The results of expressing patient outcome are compared using two staging systems: localized, regional, and distant (LRD) and the TNM of the American Joint Committee on Cancer (AJCC). Expressing patient outcome depends on the staging system used. There is overlap between the stage definitions of the LRD and the TNM. A single stage in the LRD may include more than one stage grouping of the TNM and vice versa. For most sites, "localized" provides lower survival rates than stage I of the TNM. The TNM provides more precise information about prognosis because its definitions reflect the latest survival information and diagnostic technology. Time trends can be measured only with the LRD because of its stability over the years. The precision of the TNM has been achieved at the expense of time trend analysis. The LRD is usually not an acceptable end point for the assessment of early cancer detection. PMID- 1615265 TI - Staging patterns and early cancer detection. AB - There is a great deal of indirect, nonexperimental evidence that a pattern of earlier-stage disease at diagnosis has a better outcome. Increased early detection activities can change, these stage patterns while various biases and the question of generalizability need to be kept in mind in their interpretation. The indirect evidences of possible benefit from early detection activities includes an increase in the number of cases detected, a pattern of more early- and less advanced-stage cases, an increase in the overall site-specific survival rate, and a decrease in the case fatality rate. Unless these intermediate markers are favorable, it is unlikely that early detection will reduce mortality. In addition, one should also differentiate a reduced incidence or a change in treatment as a cause for reduced mortality. PMID- 1615266 TI - Staging of head and neck cancer. AB - Revised staging systems for cancers of the upper aerodigestive tract, the major salivary glands, and the thyroid are presented. The staging has been accepted by both the American Joint Committee on Cancer and the International Union Against Cancer and is gaining worldwide acceptance. PMID- 1615267 TI - Role and extent of lymphadenectomy for early breast cancer. AB - A better understanding of the locoregional and systemic approaches to breast cancer over the past decade and one-half has altered the perspective on surgical management of the axilla. An increased awareness of the importance of early diagnosis and appropriate staging has focused further attention on the extent of resection of axillary lymph nodes. Examined here are the anatomy and physiology of the axillary lymph nodes, their clinical evaluation, the significance of histologic evaluation, a discussion of the procedure's role in staging and therapy, and a presentation of the complications of axillary lymph node dissection. It is in this light that we discuss the extent of axillary lymphadenectomy in early diagnosis of breast cancer. PMID- 1615268 TI - How staging directs treatment for esophageal and lung cancer. AB - While staging systems may seem complicated and cumbersome at times, they are designed to stratify patients into groups by prognosis and treatment. This article reviews the staging of lung cancer and esophageal cancer, and it shows how this classification translates into different treatment plans based upon this staging. PMID- 1615269 TI - Staging of colorectal cancer. AB - A chronological overview of the various staging systems for colorectal cancer is presented in an effort to demonstrate the reason for the current state of confusion. The Dukes 1932 system is considered to be the gold standard because of its simplicity and accuracy and is the system most often referred to in the literature. Number of positive nodes and depth of invasion are two variables that have been found to be predictors of survival. In the future, other prognostic factors such as nuclear morphology, flow cytometric characteristics, histological grade, and vascular or lymphatic invasion may also be entered into the staging equation. Use of the TNM system at this time is recommended since it most completely describes appropriate prognostic factors and allows conversion of other staging systems into a common format. Future modifications could logically evolve from the TNM system. PMID- 1615270 TI - Sarcoma management based on a standardized TNM classification. AB - The proper management of soft tissue sarcomas, that offering the highest cure rate while attempting limb sparing should the extremities be involved, requires a standard approach best achieved with the TNM classification. Such staging of the sarcomatous lesion is based primarily on the histologic grade, followed by size and finally histologic classification. The definitive approach is surgical, with muscle group dissection employed at all sites, including the extremities, trunk, and head and neck region. Radiation therapy alone or in combination with chemotherapy improves survival in all high-grade lesions at risk for recurrence. Evaluation of the primary and recurrent lesion by computed tomography, magnetic resonance when necessary, and angiography offers the best approach for evaluation of the lesion in treatment planning. PMID- 1615271 TI - [Chorionic villi sampling and prenatal diagnosis]. AB - The authors report their experience of 790 villous specimens taken either early (for 430 cases) or late (360 cases) between 10 and 37 weeks of amenorrhea (WA) using a transabdominal syringe. In the early choriocentesis cases, they conclude that use of the transabdominal route after 12.5 WA, regardless of the position of the chorion, makes it possible significantly to reduce the rate of fetal loss which becomes similar to that for amniocentesis. Placentocentesis has been used at later stages, either for high-risk couples as an alternative to amniocentesis (183 cases), or in cases of ultrasound abnormalities (177 cases) as an alternative to amniocentesis or cordocentesis. Placentocentesis makes it possible to obtain the fetal karyotype very rapidly within 1 to 2 days. PMID- 1615272 TI - [Induction in the scarred uterus]. AB - Labor was induced in 41 women with uterine scarring and a fetus in the cephalic presentation and normal pelvis size. Due to various problems, these patients would have had to undergo cesarean section if this alternative had not been attempted. The use of prostaglandins E2 to increase maturation of the cervix, of Syntocinon and peridural analgesia made it possible to obtain delivery through the genital tract in 24 cases with the same level of fetal morbidity as for the babies delivered by cesarean. PMID- 1615273 TI - [Perineal rehabilitation of female urinary incontinence. Long term results]. AB - The results of perineal rehabilitation in 101 women with urinary incontinence are evaluated with a follow-up of 18 months (9-37 months). The authors try to precise the clinicals and urodynamicals initials factors of a bad pronostic. PMID- 1615274 TI - [Menopause and cardiovascular risk factors. Influence of treatments]. AB - Along with menopause goes an increase of cardiovascular heart disease risk, and at the same time a change in certain risk factors. Those risk factor changes are analysed. The most obvious change is cholesterol increase, mostly on its LDL fraction linked to a decrease of its regular epuration. Today, the influence of replacement therapy on cardiovascular heart disease risk is not well known, and this is due mostly to the fact that there are no randomized studies. Thus exists a selection of women with low risk levels, either at the beginning or during follow-up. As a consequence results are necessarily optimized. It is possible to extrapolate the risk factor evolution under treatment only if its mechanism is known. Thus, when estradiol is given not the oral route, lipidic balance is brought back to its premenopausal state, without any noticeable influence on other known risk factors. It is thus reasonable to see there a favorable influence. When estradiol or any other similar molecule is given the oral route, one can notice, depending on the dose and the molecule, similar changes, along however with other variations which actual consequences remain unknown, like the increase of certain coagulation factors, of angiotensinogen, of triglycerides on HDL cholesterol. In particular, one does not know if those last pharmacological changes do not have a negative effect on predisposed patients. PMID- 1615275 TI - [Management of the scarred uterus]. AB - On the basis of 899 cases of uterine scarring following cesarean section, the authors carried out a prophylactic cesarean in 42% of cases. Labor ended in childbirth by the genital tract in 44% of cases. The very low incidence of uterine rupture since segmental hysterotomy has become widespread and the improved fetal and maternal prognosis are all reasons to prefer delivery by the genital tract. One of the factors in choosing the method of childbirth is radiopelvimetry and estimation of the fetal weight; however, the suspicion of a threshold pelvis is not a contraindication to the labor test which was successful in 70% of the authors cases. On condition that strict obstetrical monitoring is possible, oxytocic drugs can be used to induce labor or correct hypokinesia and to administer a peridural analgesic. Routine extraction is no longer necessary during the expulsion phase but the authors remain faithful to uterine revision. In general, the labor test should be suggested as often as possible and should receive the same monitoring and treatment methods as for an intact uterus. PMID- 1615276 TI - [Hydrops fetalis of non-immunological origin. Study of 24 cases and review of the literature]. AB - Twenty-four cases of Schriddes' disease of non-immunological origin were observed between 1973 and 1990 in the Gynecology-Obstetrics Service at Angers (France). These cases are analyzed and the results are compared with those published in the literature. This disorder must be diagnosed before birth. Three examinations are currently essential for foetal assessment: obstetrical ultrasound, ultrasonic cardiography and amniocentesis. As a result of improved antenatal diagnosis, the question of the indications for in-utero treatment and medical termination of pregnancy now arises. Despite progress in neonatal resuscitation, the prognosis generally remains very poor. PMID- 1615277 TI - [Ruptured tubal pregnancy associated with an evolving uterine pregnancy. Case report and review of the literature]. PMID- 1615278 TI - [The combined pregnancy. Review of the literature with regard to a case report]. PMID- 1615279 TI - [Associated rectal and genital prolapse: value of Delorme's operation. A case report]. AB - Rectal prolapse is a rare disorder, which usually affects patients suffering from genital prolapse (rectal prolapse is associated with genital prolapse in 50% of cases). On the basis of a study of the literature and with regard to one case history, the authors set out to explore the simplest and most effective way of treating these two disorders simultaneously. The treatment remains surgical and should combine treatment of the genital prolapse by vaginal route with treatment of the rectal prolapse by means of the Delorme operation. The mortality and morbidity rates are zero if this operation is used and the relapse rate is only 8 to 11% for the rectal prolapse. It would appear that the two approaches are rarely associated by the authors and would seem to be interesting to reconsider this question by indicating mixed treatment of the two prolapses whenever possible. PMID- 1615280 TI - Binding of a bacterial acylpoly(1,3)galactoside to human blood leucocytes. AB - The binding of a 34-kDa (mol. wt.) acylpoly(1,3)galactoside (APG) extracted from a membrane proteoglycan of Klebsiella pneumoniae to human blood leucocytes was investigated. APG is made of a long poly(1,3)galactose chain, a core-like region and a lipid moiety which comprises two glucosamine residues bound to a phosphate group and two beta OH myristic acids. Fluoresceinated APG was shown to bind preferentially to monocytes and to a lesser extent to polymorphonuclear neutrophils, as determined by flow cytometry. Binding of fluoresceinated APG was inhibited by unlabelled APG; it was concentration dependent, but not saturable, with rapid kinetics. It occurred at +4 degrees C but was markedly increased at 37 degrees C. It involved trypsin-sensitive molecules on the membrane of monocytes. Neither the parent proteoglycan nor lipopolysaccharide from K. pneumoniae or Salmonella minnesota competed for APG binding. A minor non-specific binding to lymphocytes, occurring predominantly on B cells, was observed. Unlike that of lipopolysaccharide, the APG binding was not blocked by polymyxin B sulphate. Interaction between the galactose chain of APG and the galactose receptor does not account for the binding of APG to monocytes because the galactose receptor (Mac-2) is expressed at high density on activated macrophages but not on monocytes. Despite its strong binding to human blood monocytes, APG displayed a much weaker activity than K. pneumoniae membrane proteoglycan with respect to induction of monocyte cytokine synthesis. When administered as a Technetium 99 conjugate, APG was shown to label inflammatory foci in experimental animals, and its property as a marker of macrophages is currently being evaluated in clinical trials. PMID- 1615281 TI - Common variable immunodeficiency with increased surface IgM-positive double bearing B cells. AB - We report a case of common variable immunodeficiency (CVI) that shows low levels of IgG and IgA, but a normal quantitative or qualitative level of IgM. T-cell functions were not disturbed. Increased numbers of surface IgM (sIgM) and sIgD, sIgM and sIgG, sIgM and sIgA double-bearing B cells were observed as compared with a control. No IgG and IgA induction upon stimulation with Staphylococcus aureus Cowan I (SAC) and recombinant interleukin-2 (rIL-2), or pokeweed mitogen (PWM) and rIL-4 or rIL-6 was observed, although there was proliferation. Although mu mRNA was expressed as much as in a healthy control, transcription of gamma mRNA and alpha mRNA was very low. Furthermore, no enhanced effects of gamma mRNA and alpha mRNA were recognized upon stimulation with rIL-4 and rIL-6. These results suggest that the patient's B cells might be defective at the switching process from mu, mu and delta, mu and gamma to gamma or mu and alpha to alpha. PMID- 1615282 TI - Association of the mycobacterial 30-kDa region proteins with the cutaneous infiltrates of leprosy lesions. Evidence for the involvement of the major mycobacterial secreted proteins in the local immune response of leprosy. AB - The granulomatous skin lesions of human leprosy are known to be due to the cutaneous immune reaction to various mycobacterial antigens. In the present study, by immunohistochemical analysis using a previously characterized monoclonal antibody (MoAb) 3A8 we have demonstrated a selective expression of the 3A8 epitope of mycobacterial 30-kDa proteins, the major secreted proteins of mycobacteria, in various forms of leprosy lesions across the clinical spectrum. The localization of MoAb 3A8 staining is confined to the areas of cellular infiltrates of the lesions. In tuberculoid lesions the intense 3A8 staining was seen mostly in association with the membrane of the dermal cellular infiltrates whereas in highly bacilliferous lepromatous lesions the staining seems to be diffused with granular appearance but not in the form of bacteria. In patients with reversal reaction the staining was specifically extended to cells infiltrating the epidermis. MoAb 3A8 did not show any reactivity with inflammatory skin lesions of patients other than those with leprosy. Since the 3A8 epitope of 30-kDa proteins has been shown to be present in all cellular compartments of the mycobacteria and in the actively secreted BCG 85 antigen complex, MoAb 3A8 reactive protein(s) in leprosy lesions may be derived either from degraded somatic mycobacterial products or from antigens actively secreted by live bacilli. The latter could be true in the cases of untreated lepromatous lesions with high bacterial load since live M. leprae has also been considered to secrete corresponding 30-kDa proteins similar to other closely related mycobacteria. By double immunoenzyme staining we clearly demonstrate the expression of 3A8 epitope on CD68+ macrophages in the granulomas of tuberculoid leprosy, whereas in highly bacilliferous lepromatous lesions most of the double staining was seen in a diffuse pattern within the interstitial space of the cellular infiltrate as well as in the cytoplasm of CD68+ macrophages. In lesions from reversal reaction the 3A8 epitope is more strongly expressed on CDla+ dendritic Langerhans cells (LC) both in the epidermis and in the dermis as compared with other types of leprosy. This provides evidence for the involvement of LC in handling of mycobacterial antigenic epitopes in leprosy lesions. Further, immunoenzyme double staining revealed that the expression of this mycobacterial 3A8 epitope on antigen presenting cells such as CD68+ macrophages and CDla+ LC is present in juxtaposition with CD3+ T cells including the alpha beta and gamma delta receptor-bearing T cells in the granuloma.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1615283 TI - Adjuvant composition determines the induction of type II collagen-induced arthritis. AB - In this study we have investigated the influence of adjuvant composition on the development of collagen-induced arthritis and of anti-collagen type II specific B and T-cell responses following immunization with type II collagen. DBA/l mice immunized with bovine collagen type II emulsified in complete Freund's adjuvant (CFA) containing Mycobacterium tuberculosis strain H37Ra developed footpad swelling indicative of arthritis. Animals immunized with collagen type II plus CFA containing Mycobacterium butyricum, or incomplete Freund's adjuvant showed no significant increase in footpad width. Induction of anti-CII specific T-cell proliferation was also dependent upon immunization with CII plus CFA containing M. tb H37RA. In contrast, ovalbumin-reactive T-cell proliferation was unaffected by the species of mycobacteria, indicating that the difference in adjuvant activity of the mycobacterial species is specific for anti-collagen type II T cell responses. Antibody response to collagen type II, unlike T-cell responses, was not significantly different using the two adjuvants. This study therefore demonstrates that murine collagen-induced arthritis requires immunization with collagen type II together with complete Freund's adjuvant containing Mycobacterium tuberculosis H37RA. Since only this combination of antigen and adjuvant induces detectable arthritis and T-cell responses against collagen type II, while antibody synthesis does not have such stringent adjuvant requirements, this suggests that the development of the full pattern of the collagen-induced arthritis disease requires synergistic activation of both humoral and cell mediated responses. PMID- 1615284 TI - Immunoglobulin G, A, and M light chain ratios in some humoral immunological disorders. AB - The total kappa/lambda immunoglobulin light chain ratio and the kappa/lambda ratios within each of the serum immunoglobulin classes G, A, and M were measured in thirteen patients with humoral immunological disorders. Of those patients, eight had common variable immunodeficiency whereas five patients had other forms of humoral immunological deficiencies. Eleven patients had abnormal antibody response in vivo. All but three of the thirteen patients had clearly abnormal light chain ratios in one or more of the immunoglobulin classes. We conclude that humoral immunological disorders, usually characterized by abnormal heavy chain production and a disturbed antibody response, may frequently have a concomitant abnormal synthesis of the light chains resulting in an abnormal kappa/lambda light chain ratio. PMID- 1615285 TI - The implications of the failure to generate autoantibody-producing hybridomas from rat erythrocyte-immunized mice. AB - Injection of mice with rat erythrocytes (RRBC) has long been thought to provide an experimental model in which suppressor T cells (Ts) control autoimmunity. The basis of this is that whilst mice immunized with RRBC produce an antibody response, of which a proportion cross-reacts with autologous red cells, the RRBC immunized recipients of RRBC-primed spleen cells make no, or little, autoantibody, and secondly because the transfer of this autoantibody-specific suppression can be abrogated by T-cell depletion of transferred spleen cells. Here an alternative explanation of these phenomena is described. PMID- 1615286 TI - Affinity purification of antigen-specific serum immunoglobulin from the European eel (Anguilla anguilla). AB - Immunization of specimens of the European eel with a hapten-carrier conjugate resulted in a significant rise in anti-hapten titres. Antigen-specific immunoglobulin was purified on a matrix onto which the hapten-carrier conjugate had been immobilized. Rabbit antisera raised against the product of the affinity purification recognized two molecular moieties. The first was eel immunoglobulin as inferred by the polypeptide composition, i.e. disulphide-linked heavy and light chains of 72 kDa and 25 kDa respectively. The second was a 110-kDa protein. A 800-kDa and a 400-kDa molecular form of eel immunoglobulin were disclosed by a combination of gel filtration and immunoelectrophoretic detection. The latter was the more abundant serum form. The 110-kDa protein was found non-covalently associated with the 400-kDa immunoglobulin. Both molecular forms of immunoglobulin from immune sera exhibited antigenic specificity and reactivity. PMID- 1615287 TI - Recombinant vaccine vector-induced protection of athymic, nude mice from influenza A virus infection. Analysis of protective mechanisms. AB - Athymic, nude mice, which normally succumb to virus infection, can resolve infection with recombinant vaccinia virus (rVV) engineered to express IL-2. We have demonstrated that interferon-gamma (IFN-gamma) produced by natural killer (NK) cells and other immunocytes in response to the virus-encoded interleukin-2 (IL-2) is crucial to recovery. Here, we extend this work to show that nude mice, when primed intravenously with rVV co-expressing both IL-2 and an influenza virus haemagglutinin (HA) gene, are also protected following challenge with a lethal dose of homologous influenza virus. A substantial increase in the number of influenza virus-reactive antibody-secreting cells producing antibody of the IgM isotype, but not of the IgG or IgA isotypes, was found in spleens and lungs of the protected mice. Treatment with monoclonal antibodies to IFN-gamma or to the NK marker, as GM1, at challenge and thereafter, led to their death however, though the specific IgM antibody response was unaffected. These data suggest that both specific antibody and non-specific antiviral reactivity are important elements of the protective response and show that this immunization strategy may be used to protect severely immunocompromised individuals. PMID- 1615288 TI - Mortality among workers engaged in the development or manufacture of styrene based products--an update. AB - Mortality was updated another 11 years through 1986 for a previously studied cohort of 2904 male chemical workers who were potentially exposed to styrene and related materials for a year or more between 1937 and 1971. Substantial deficits in mortality from all causes and total cancer were observed in the cohort when it was compared with white males in the United States, and also other chemical workers who were unexposed to styrene-based products. Mortality from leukemia was slightly less than expected during the updated period, in contrast to an excess of lymphatic leukemia observed in the original period. Yet small elevations in risk of other types of lymphatic cancer, particularly multiple myeloma, persisted. The risk of these cancers did not increase with estimated intensity or duration of styrene exposure. The findings are discussed in context with those of studies of similarly exposed workers in related industries. PMID- 1615289 TI - Mortality of workers employed at organochlorine pesticide manufacturing plants- an update. AB - A previous mortality study among four organochlorine pesticide manufacturers was updated through 1987. The organochlorine pesticides included chlordane; heptachlor and endrin; aldrin, dieldrin and endrin; and dichlorodiphenyltrichloroethane. The mortality for all causes and all malignant neoplasms at each of the plants was lower than expected. There was a statistically significant increase in liver and biliary tract cancer among workers at plant 3 (5 observed, standardized mortality ratio 393, 95% confidence interval 1.27-9.20). These results are somewhat consistent with experimental animal findings showing benign and malignant tumors of the liver after exposure to aldrin and dieldrin. However, the deaths were due to a mixture of intra- and extra-hepatic tumors, and the dose-response analysis was limited because of the small number of deaths and lack of exposure data. Additional study of this group should include continued follow-up of the total cohort and a case-referent analysis of the deaths from liver and biliary tract cancer. PMID- 1615290 TI - Mortality among workers in a thorium-processing plant--a second follow-up. AB - A second follow-up of mortality was carried out for workers employed in a thorium processing plant between 1915 and 1973. The study group comprised 3796 workers (3119 men and 677 women). Of the whole group, 926 (761 men and 165 women) were deceased and 2620 (2161 men and 459 women) were still alive, while 250 (6.6%) were lost to follow-up. For the male workers, the standardized mortality ratio (SMR) for all causes of death was 1.12 with a 95% confidence interval (95% CI) of 1.05-1.21. The SMR for the male workers was also significantly increased for all cancers (SMR 1.23, 95% CI 1.04-1.43) and lung cancer (SMR 1.36, 95% CI 1.02 1.78). For the female workers, the SMR was 0.74 (95% CI 0.63-0.86) for all causes and 0.53 (95% CI 0.35-0.78) for all cancers. The results of a Poisson regression analysis showed that there was no significant effect of the selected factors on lung cancer mortality. PMID- 1615291 TI - Adverse pregnancy outcome and childhood malignancy with reference to paternal welding exposure. AB - Welding may deteriorate spermatogenesis and increase reproductive failures. This study examines reproductive end points in a Danish cohort of 10,059 metalworkers who fathered 3,569 children in 1973 through 1986. Occupational histories were gathered by postal questionnaires. Information on pregnancy outcomes and offspring was obtained by record linkage to medical registers. The occurrence of reduced birthweight, preterm delivery, infant mortality, and congenital malformation was not increased among children at risk from paternal welding exposure in comparison with children not at risk. The overall incidence of childhood malignancies among 23,264 children born in 1968 through 1986 with a total of 259,113 person-years of follow-up was equal to national rates (relative risk 0.97, 95% confidence interval 0.63-1.42). However, pregnancies preceding a birth at risk from paternal exposure to stainless steel welding were more often terminated by spontaneous abortion (odds ratio 1.9, 95% confidence interval 1.1 3.2). This finding needs cautious interpretation and should be further investigated in future studies. PMID- 1615292 TI - Differences in the incidence of myocardial infarction among occupational groups. AB - An inverse relationship between social class and coronary heart disease has been observed in several countries, but few studies have investigated the incidence of this disease over different occupational groups. A case-referent study was carried out to estimate the relative risk of a first myocardial infarction in various occupational groups. Cases of myocardial infarction (N = 36,602) were identified from both hospital discharge and death records. Two referents for each case were randomly selected from the study base. Information about occupation was obtained from two consecutive censuses. An increased incidence, compared with that of others employed, was found for persons in some occupations in production work, transport work (men), and service work (women). Low relative risk were found mainly for persons in occupations demanding a high education. The relative risks ranged from 0.3 to 2.8. Several factors, occupational as well as nonoccupational, may be of importance in explaining the findings. PMID- 1615293 TI - Design of check-out systems including laser scanners for sitting work posture. AB - Forty-six laser scanner operators were compared with 106 cashiers operating conventional cash registers. The influence of job rotation on the two groups was evaluated, and several design features were examined. For this purpose the prevalence of musculoskeletal disorders was determined by means of a questionnaire and a physical examination. In addition, a three-dimensional movement analysis system was employed. Work postures were analyzed with the Ovako working analysis system. The results indicate that a beneficial effect on the musculoskeletal system is achieved by combining the operation of a laser scanner with job rotation. The study also points out the need for better equipment, including flat scanners and smaller keyboards, and a change in the angle between the scanner and the take-off belt running up to the cashier. PMID- 1615294 TI - Effects of perceived job stress on depressive symptoms in blue-collar workers of an electrical factory in Japan. AB - This three-year prospective study on the effects of job stress on depressive symptoms over time was conducted among male blue-collar workers in an electrical factory in Japan. Data were collected at yearly intervals by means of postal questionnaires. Initially ten job stress variables, five major covariates, and depressive symptoms (Zung Self-Rating Depression Scale) were measured. In the yearly examinations, depressive symptoms were measured for a total of 468 respondents. The results indicated that job unsuitability was a significant predictor of depressive symptoms in the second and third year, after control for the initial covariates and depressive symptoms. Lack of control over workplace and poor human relations at the workplace were significantly associated with depressive symptoms after one and two years, respectively. Job unsuitability and poor human relations at the workplace seem to be risk factors for long-lasting depressive symptoms in Japanese blue-collar workers. PMID- 1615295 TI - Cancer mortality among licensed herbicide applicators. AB - This retrospective cohort study investigated the cancer mortality of 1341 herbicide applicators licensed before 1 January 1980. The cohort was followed for mortality until 1 January 1988 by means of the Dutch system of population registers. For the subjects who died before 1 January 1988 the cause of death was obtained from the Central Bureau of Statistics. The cause of death was obtained for 98.4% of the deceased subjects. The total mortality was lower than expected according to mortality rates of the total male Dutch population. The total number of deaths from cancer was however slightly higher than expected [standardized mortality ratio (SMR) 114]. Mortality from several subtypes of cancer was also higher than expected, that for multiple myeloma being statistically significantly higher than unity (SMR 815, 95% confidence interval 164-2382). Occupational exposure to herbicides appears to increase the risk for multiple myeloma and possibly other malignant neoplasms. PMID- 1615296 TI - [Cerebral trypanosomiasis: epidemiology, clinical aspects, therapy and illness course]. AB - More than 20,000 people are infected with one of the two forms of African trypanosomiasis each year. Without treatment the outcome is almost always fatal. There are, however, problems involved in drug treatment. Reactive encephalitis is recorded in up to 18% of all cases treated for cerebral trypanosomiasis. Recently a lack of response to treatment has been reported with increasing frequency from endemic areas. Relapses occur in up to 10% of cases. Reasons for relapses include insufficient treatment due to poor compliance or lack of drugs, reinfection in endemic areas, pharmacokinetic problems, the parasite's evasive mechanisms, and primary and/or secondary drug resistance. PMID- 1615297 TI - Cerebral malaria. AB - Cerebral malaria is the most important manifestation of severe Plasmodium falciparum infection. The clinical picture in South East Asian adults differs from that in African children. The children are more likely to have abnormal brain stem reflexes, signs suggestive of cerebral herniation, and raised CSF opening pressure, and to suffer persistent neurological sequelae. The mortality remains high at about 20%. The diagnosis must be considered in all patients with fever and impaired consciousness who may have been exposed to the infection. The pathophysiology of cerebral malaria may involve mechanical obstruction of the cerebral circulation by parasitized erythrocytes which have adhered to the vascular endothelium. Cytokines such as tumor necrosis factor may also contribute. The most important element of treatment is early, optimal chemotherapy with quinine, but artemisinine derivatives may prove even more effective. PMID- 1615298 TI - [Spongiform encephalopathies with special reference to bovine spongiform encephalopathy]. AB - In Switzerland bovine spongiform encephalopathy (BSE) was detected for the first time in November 1990. It is a transmissible disease of the central nervous system similar to Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome (GSS) and kuru in man, and, in animals, scrapie in sheep and goats, chronic wasting disease (CWD) in captive mule deer and elk of North America and transmissible mink encephalopathy (TME) of farm reared mink. The infectious agent of the spongiform encephalopathies (SEs) is extremely small (greater than 100 microns) and very resistant against physical and chemical disinfectants. The infectiousness is closely linked to the so-called prion proteins, the biological and genetic properties of which are not yet fully understood. The first outbreak of BSE occurred in England, and the disease spread rapidly all over Great Britain. The source of infection proved to be bone and meat meal obtained from scrapie-infected slaughter wastes. So far we have diagnosed 17 cases of BSE in our country. The risk of humans contracting CJD by ingestion of meat, milk and their products contaminated with BSE is probably minimal. PMID- 1615299 TI - Neurocysticercosis. An introduction with special emphasis on new developments in pharmacotherapy. AB - Neurocysticercosis is the most important parasitic infection of the nervous system in countries of the third world. The disease is caused by the cystic larval stage of Taenia solium, the pork tape worm. The clinical picture of neurocysticercosis is due to the parasite itself and/or an inflammatory reaction around degenerating cysts in the central nervous system. It may cause epilepsy, chronic meningitis and hydrocephalus. The diagnosis is greatly facilitated by the use of computer tomography, magnetic resonance imaging and serological tests. Praziquantel and albendazole now offer a reasonable treatment for neurocysticercosis. However, the effect of praziquantel is largely dependent on its bioavailability, which is decreased by the use of antiepileptics and, possibly, dexamethasone. Albendazole is associated with side effects on bone marrow and liver, and it has teratogenic and mutagenic properties. Both drugs act poorly on intraventricular cysts. Coadministration of cimetidine with praziquantel leads to a significant two-and-a-half times' increase of the latter drug's bioavailability. This resulted in a good clinical response to treatment for 12 patients with various forms of neurocysticercosis. Although neurocysticercosis is no longer endemic in many Western European countries, its incidence is likely to increase due to increased travel to, and immigration from, endemic countries. PMID- 1615300 TI - [Strongyloidiasis under immunosuppressive therapy]. AB - Strongyloidiasis is a parasitic disease of tropical regions and to some extent of the South of Europe. In immunocompromised patients, particularly under steroid medication, infestation by this nematode may sometimes lead to life-threatening hyper-infestation. Diagnosis is often difficult because of a polymorphic clinical picture and usually low larvae excretion in the stool. The case is reported of a Yugoslavian patient who under corticosteroid therapy suffered from severe diarrhea and dehydration due to hyperinfestation by nematode larvae. Several attempts at treatment were necessary to eradicate the infestation. PMID- 1615301 TI - [The use of echocardiography in intensive care medicine]. AB - Transthoracic echocardiography is an easily accessible, non-invasive imaging procedure for evaluation and follow-up of critically ill patients. It is particularly helpful in evaluating patients with thoracic pain, low-output syndrome or heart murmur, and has prognostic value in acute myocardial infarction. It makes a diagnostic contribution in 60 to 90% of cases, and has therapeutic implications in 50 to 65%. New ultrasound technics are briefly discussed. PMID- 1615302 TI - [Vasculitic skin lesions caused by nonsteroidal anti-inflammatory agents]. AB - Today, non-steroidal anti-inflammatory drugs are very frequently prescribed agents. These drugs are responsible for side effects which are rarely recognized and poorly understood. One of these side effects is leukocytoclastic vasculitis with or without skin ulcerations. Rheumatoid arthritis and other mixed connective tissue diseases may also lead to vasculitis ulcerations, which explains the difficulty of correct diagnosis in each case. In addition, disease-modifying drugs such as methotrexate, frequently used in the above-mentioned syndromes, further complicate the situation because these agents may also produce vasculitis. In the present case study we analyze and discuss the diagnosis and follow-up in three of our patients with vasculitis skin ulcerations. In two of them, the vasculitis was attributed to the use of naproxen. Despite thorough examination and documentation of all three cases, etiologic evaluation was difficult and complex. PMID- 1615303 TI - [Anemia-inducing colonic diverticular hemorrhages]. AB - 20 patients with massive lower gastrointestinal bleeding caused by segmental or total colonic diverticular disease are presented. The bleeding source was localized by colonoscopy, angiography and intraoperatively in 5, 5 and 2 patients respectively. The hemorrhage occurred in the right colon in 9 patients and in the left colon in 3 patients. Due to ongoing bleeding 9 patients needed immediate surgery (7 right hemicolectomies, 1 left hemicolectomy, 1 sigmoidectomy). The median transfusion requirement of operated individuals was 14 units of blood. 2 (22%) patients died from postoperative complications. The remaining 7 patients had no recurrent bleeding during a median follow-up of 3.5 years (0.5-9 years). 11 patients with arrested bleeding (median transfusion requirement 3 units of blood) were treated conservatively. During a mean follow-up of 4.5 years (1.5-10 years) only one (9%) of the conservatively treated patients complained of recurrent bleeding requiring sigmoidectomy. We conclude that massive and ongoing hemorrhage (greater than 6 units of blood) occurs predominantly in right-sided colonic diverticula and requires immediate surgery. Arrested bleeding (transfusion requirements less than 6 units of blood) from colonic diverticula can be treated conservatively since operative mortality is high and recurrent bleeding is rare. PMID- 1615304 TI - [Age- and sex-specific standard values of colonic transit time in healthy subjects]. AB - Use of radiopaque markers with a plain X-ray of the abdomen is a simple technique to measure mean segmental and total colonic transit time. We evaluated 128 healthy volunteers with a mean age of 40 years (range 20-81 years) from three different parts of Switzerland to assess age and sex specific normal transit times. In men and women colonic transit time was not influenced by age. The mean transit time was significantly shorter in men than in women (30 +/- 2 hours versus 41 +/- 3 hours: p less than 0.05). In men the transit time was also influenced by smoking. Non-smoking men had a significantly shorter transit time than smokers (26 +/- 2 hours versus 40 +/- 5 hours: p less than 0.05). In women, neither smoking nor the menstrual cycle influenced transit time. For normal colonic transit time we recommend up to 66 hours for smoking men, up to 44 hours for non-smoking men and up to 70 hours in general for women. PMID- 1615305 TI - [Liposarcoma of the laryngeal region. Case report and literature review]. AB - The case is reported of a 64-year-old man in whom a pedunculated tumor of the Vallecula epiglottica occurred and was excised. Histologically it proved to be a dedifferentiated liposarcoma. The patient is well and free of disease 18 months later. The literature is reviewed and 20 other cases of liposarcoma in the laryngeal region are discussed. PMID- 1615306 TI - Accumulation of copper, lead, manganese and iron by field populations of Hydrodictyon reticulatum (Linn.) Lagerheim. AB - The potential of 'water-net' Hydrodictyon reticulatum to accumulate copper, lead, manganese and iron was determined in seven polluted water bodies having different physicochemical characteristics. The lead accumulation was linearly related with ambient concentration whereas in case of copper, manganese and iron it was maximum at lowest ambient level of metals. Investigations on response of alga to various concentrations of test metals under single metal treatments revealed that the algal cells are saturated at high equilibrium concentration of greater than 0.5 (lead), greater than 2.5 (copper and iron) and greater than 5.0 (manganese) mg/l. Alkaline pH favoured accumulation of these metals under field conditions. Alga showed high concentration factor (Cf) for all the metals both under field and laboratory conditions. However, Cf value was higher in case of manganese and iron in natural populations. Results indicate the possibility of using this alga in waste water treatment programmes. PMID- 1615307 TI - Aerosols characterization in a forested site in Quebec, Canada. AB - Three AERAS low pressure 11 stage cascade impactors with rotatable collecting plates (LPCR) were installed at the Duchesnay forest station near Quebec City and four low pressure inertial collectors (LPIC) were installed in the forest. The analysis of the aerosol deposits was performed by static fast atom beam mass spectroscopy (FABMS); SIMS and ESCA analyses were also made. The morphological characterization and the elemental volumetric composition of the aerosols were established by a scanning electron microscope equipped with an X-ray dispersive energy analyser. Micro-weighting of the aluminium substrate before and after the sampling by the AERAS impactor enabled the study of the mass-size-distribution of the aerosols according to their aerodynamic equivalent diameter. Example of the results obtained are presented in relation to air parcels' trajectories. This study has shown that it is possible to characterize the aerosols according to the origin and trajectories of the air mass with which they travel; sources along the tracks have been shown to contribute to the aerosol loading of the air masses. PMID- 1615308 TI - Geochemical prospection of cadmium in a high incidence area of prostate cancer, Sierra de Gata, Salamanca, Spain. AB - A high incidence of prostate cancer was observed in some areas of Salamanca province, Spain. After excluding the most common etiological factors as the cause, it is concluded that the only possible risk factor must be due to the presence of some environmental carcinogen. In view of the etiological relationship between Cd and the pathological state, a study was carried out on the geochemistry of this element in the area. Anomalous amounts of Cd were found in stream sediments. This anomaly does not correspond to human activity, but rather to high regional amounts of cadmium in the substrate. Thus, the contents of Cd in soils developed over substrates containing naturally-occurring anomalous amounts of cadmium and the concentration in underground waters should be considered as a risk factor in this area. PMID- 1615309 TI - Lead concentration and delta-aminolevulinic acid dehydratase activity in the blood of the general population of Tarragona Province, Spain. AB - Blood samples were collected from 488 people living in an industrial and an agricultural area of Tarragona Province, Spain. The samples were subjected to blood lead analyses by atomic absorption spectrophotometry. Although in the industrial area men had higher blood lead levels than women, this difference was not statistically significant. Blood lead concentrations were related to a range of factors such as age, smoking and drinking habits. Both smoking and drinking habits were associated with a dose-dependent increase in blood lead levels, especially in men. On the other hand, delta-aminolevulinic acid dehydratase (ALA D, EC 4.2.1.24) activity was determined in blood from 186 people of Tarragona Province. The results obtained were within the normal limit values (NLV) as defined by the WHO. The present data concerning Tarragona Province show that in relation to environmental health there is not a serious problem from lead contamination. PMID- 1615310 TI - Geographical and temporal patterns of air-borne and personal 1,1,1 trichloroethane exposure in Piedmont region (Italy). AB - During the summer of 1989 and the winter 1989-1990, we initiated measurements of 1,1,1-trichloroethane concentrations in indoor, outdoor, and 'personal' air, in urban and rural sites. In the Piedmont region (North-Western Italy) we have carried out an atmospheric monitoring study: in the centre of Turin city (urban site), in Cuorgne (rural site), and in Banchetta (remote site). First results confirm a higher winter contamination (11.67 vs. 2.79 micrograms/m3) and a higher contamination at the urban site, compared to rural and remote sites. Excluding Cuorgne in the summer, all indoor/outdoor ratios are greater than 1 and, in all cases, the 'personal' air shows higher 1,1,1-trichloroethane levels than indoor and outdoor air. In Turin the relationships between winter and summer all show a higher winter contamination, while, in Cuorgne no differences are proven. PMID- 1615311 TI - Predictive relationships for sidestream smoke cigarette yields. AB - Relationships have been sought for smoking machine generated sidestream smoke yields of cigarettes for particulate matter (water and nicotine free) (PMWNF) and nicotine. Comparisons have been made with the corresponding mainstream smoke yields, other readily measurable factors in machine smoking and with the physical characteristics of cigarettes. The sidestream smoke yields have been found to be related to the puff count during machine smoking multiplied by the cross sectional area of a cigarette or to the total weight of cigarette tobacco burnt during machine smoking. For the brands retailed in the U.K. these relationships permit calculation of the sidestream smoke contributions of PMWNF and nicotine to environmental tobacco smoke. From the data used to derive these relationships, and based on 31 cigarette brands representing 71% of cigarette sales in the U.K., the sales weighted sidestream PMWNF yield is 27.1 mg/cigarette and that for nicotine is 5.12 mg/cigarette. PMID- 1615312 TI - Polycyclic aromatic hydrocarbons, nickel and vanadium in air particulate matter in Bahrain during the burning of oil fields in Kuwait. AB - Inhalable air particulate matter (APM) was collected in Bahrain from July 31, 1991 to August 4, 1991, during the burning of the oil fields in Kuwait. The filters collected were black and the levels of APM ranged from 139 to 673 micrograms m-3 with an average value of 199 micrograms m-3. APM were analysed for their contents of PAHs, Ni and V. Analysis was carried out for 32 PAHs and total PAHs ranged from 3.1 to 9.1 ng m-3 and averaged 5.3 ng m-3. The highest individual PAH levels were benzo[ghi]perylene, benzo[b]fluoranthene, benzo[a]pyrene and indeno[1,2,3-cd]pyrene. The concentration of Ni and V ranged from 7 to 42 and 11 to 42 ng m-3, with an average value of 22 and 26 ng m-3, respectively. A strong correlation was found between Ni and V (r = 0.98, P less than 0.01). The results show that the smoke from burning oil wells in Kuwait has contributed to the concentrations of particulate matter, PAHs, Ni and V in APM in Bahrain. PMID- 1615313 TI - Increased radon concentrations in classrooms used for pottery workshops. AB - In a pilot study of nine schools the radon (Rn) concentrations were measured systematically. The mean radon concentrations in the classrooms on the ground floor and on higher floors was 52 Bq/m3, which is equivalent to the mean values in Central Europe. Several of the basement rooms used for handicraft lessons had significantly increased Rn levels with a mean concentration of 617 Bq/m3. In all other parts of the basement Rn levels were clearly lower with a mean concentration of 136 Bq/m3. In the rooms used for handicraft lessons numerous articles of pottery were on display. After removing these the Rn in air concentration was reduced to a mean value of 83 Bq/m3. PMID- 1615314 TI - Fetal tissue research. PMID- 1615315 TI - The safety of foods developed by biotechnology. PMID- 1615317 TI - New plant institute recommended. PMID- 1615316 TI - Lightning strikes the SSC. PMID- 1615318 TI - Budget ax lops off entire departments at San Diego. PMID- 1615319 TI - Motor molecules on the move. PMID- 1615320 TI - A new discipline probes suicide's multiple causes. PMID- 1615321 TI - Chaos breaks out at NIH, but order may come of it. PMID- 1615322 TI - A new blueprint for water's architecture. PMID- 1615323 TI - The role of solvent viscosity in the dynamics of protein conformational changes. AB - Nanosecond lasers were used to measure the rate of conformational changes in myoglobin after ligand dissociation at ambient temperatures. At low solvent viscosities the rate is independent of viscosity, but at high viscosities it depends on approximately the inverse first power of the viscosity. Kramers theory for unimolecular rate processes can be used to explain this result if the friction term is modified to include protein as well as solvent friction. The theory and experiment suggest that the dominant factor in markedly reducing the rate of conformational changes in myoglobin at low temperatures (less than 200 K) is the very high viscosity (greater than 10(7) centipoise) of the glycerol-water solvent. That is, at low temperatures conformational substates may not be "frozen" so much as "stuck." PMID- 1615324 TI - Probing protein stability with unnatural amino acids. AB - Unnatural amino acid mutagenesis, in combination with molecular modeling and simulation techniques, was used to probe the effect of side chain structure on protein stability. Specific replacements at position 133 in T4 lysozyme included (i) leucine (wt), norvaline, ethylglycine, and alanine to measure the cost of stepwise removal of methyl groups from the hydrophobic core, (ii) norvaline and O methyl serine to evaluate the effects of side chain solvation, and (iii) leucine, S,S-2-amino-4-methylhexanoic acid, and S-2-amino-3-cyclopentylpropanoic acid to measure the influence of packing density and side chain conformational entropy on protein stability. All of these factors (hydrophobicity, packing, conformational entropy, and cavity formation) significantly influence protein stability and must be considered when analyzing any structural change to proteins. PMID- 1615325 TI - Nuclear localization of Agrobacterium VirE2 protein in plant cells. AB - The Agrobacterium single-stranded DNA (ssDNA) intermediate T-strand is likely transferred to the plant cell nucleus as a complex with a single VirD2 molecule at its 5' end and multiple VirE2 molecules along its length. VirD2 contains a nuclear localization signal (NLS); however, because the T-strand is principally coated with VirE2 molecules, VirE2 also might assist in nuclear uptake. Indeed, VirE2 fused to a reporter protein localizes to plant cell nuclei, a process mediated by two amino acid sequences with homology to the bipartite NLS of Xenopus nucleoplasmin. Moreover, tumorigenicity of an avirulent virE2 mutant is restored when inoculated on transgenic plants expressing VirE2, supporting in planta function of VirE2. PMID- 1615326 TI - Stage-specific adhesion of Leishmania promastigotes to the sandfly midgut. AB - Although leishmaniasis is transmitted to humans almost exclusively by the bite of infected phlebotomine sandflies, little is known about the molecules controlling the survival and development of Leishmania parasites in their insect vectors. Adhesion of Leishmania promastigotes to the midgut epithelial cells of the sandfly was found to be an inherent property of noninfective-stage promastigotes, which was lost during their transformation to metacyclic forms, thus permitting the selective release of infective-stage parasites for subsequent transmission by bite. Midgut attachment and release was found to be controlled by specific developmental modifications in terminally exposed saccharides on lipophosphoglycan, the major surface molecule on Leishmania promastigotes. PMID- 1615327 TI - Reversal of the orientation of an integral protein of the mitochondrial outer membrane. AB - The NH2-terminus of the signal-anchor sequence of an integral, bitopic protein of the outer mitochondrial membrane was extended both in amino acid length (from 11 to 38 amino acids) and net charge (from +4 to +8)--changes that confer on the NH2 terminus characteristics of a strong matrix-targeting signal. The protein was inserted into the outer membrane but in an inverted orientation (Ncyto-Cin). These findings suggest that, in common with other membrane systems, the orientation of a protein in the outer mitochondrial membrane can be determined by a signal that causes retention of the NH2-terminus on the cytosolic side of the membrane. PMID- 1615328 TI - Recent advances in bone marrow transplantation. Introduction. PMID- 1615329 TI - Results of allogeneic bone marrow transplantation with unrelated or mismatched donors. AB - As most patients are not fortunate enough to have an HLA-matched sibling to use as a bone marrow donor, attention has focused on the use of either HLA-matched but unrelated donors or HLA-mismatched family members. With the maturation of the field of histocompatibility testing, it is now possible to quantitate with relative precision the degree of disparity between patient and donor. In general, it appears that with respect to histocompatibility differences between donors other than HLA-matched siblings, there is an increased incidence of acute graft versus-host disease, with the risk correlated with the degree of histoincompatibility. However, the overall disease-free survival is not always adversely affected, as a graft-versus-leukemia effect may counterbalance the increased death rate from graft-versus-host disease. To find donors for most patients, efforts are under way to recruit a large number of unrelated volunteers into the National Marrow Donor Program. PMID- 1615330 TI - Role of colony-stimulating factors in bone marrow transplantation. PMID- 1615331 TI - Bone marrow transplantation: past experiences and future prospects. PMID- 1615332 TI - The role of autologous bone marrow transplantation in the treatment of solid tumors. AB - Until effective new agents can be developed, increasing dose intensity may be the best way to improve therapy for patients who fail conventional treatment. Alkylating agents, including radiation, are likely candidates for use in dose intensive combinations. Past phase I clinical trials of single agents have redefined the maximum tolerated doses when marrow transplantation attenuates the myelosuppression. High-dose combinations of more than two agents are only possible with significant dose reductions from single-agent maximum tolerated doses. Multiple courses of therapy might permit the use of more than two agents without dose reduction. A multidrug and/or multicourse approach will probably be needed to effect curative therapy. PMID- 1615333 TI - Management of anemia in oncology. Introduction. PMID- 1615334 TI - The therapeutic role of recombinant erythropoietin in anemic patients with intact endogenous production of erythropoietin. AB - Recombinant human erythropoietin (r-HuEPO) has been shown to be remarkably effective in raising the hemoglobin concentrations and improving the quality of life of patients with chronic renal disease. It is currently under investigation for treatment of patients with nonrenal anemias associated with cancer chemotherapy, acquired immunodeficiency syndrome, rheumatoid arthritis, and other chronic illnesses. To date, investigators have shown that patients with mild anemia and low endogenous erythropoietin (EPO) production may be good candidates for such treatment. Conversely, studies have shown that patients with severe anemia and serum EPO concentrations of above 500 mU/mL apparently do not respond to doses used for patients with mild anemia or chronic renal disease. Large doses of r-HuEPO may be of use in such patients, and clinical trials are in progress to determine if it is at least possible to make these patients transfusion independent. PMID- 1615335 TI - Toward bloodless surgery: erythropoietin therapy in the surgical setting. AB - Issues related to blood safety and blood inventory have recently led to a much greater interest in blood conservation measures. Some of these measures have included using lower transfusion triggers (hematocrit values), directed donor programs, and autologous blood transfusions. When possible, autologous blood donation is the preferable alternative because it represents the safest blood, conserves blood inventories, and has a salutary effect on physician transfusion behavior. Indeed, homologous blood requirements are lowered in patients who donate autologous blood before elective surgery. However, autologous blood donation can be limited by physician underordering and an insufficient erythropoietic response to serial phlebotomy. Continuing medical education can be effectively used to alter physician behavior regarding underordering. Early clinical trials have suggested that recombinant human erythropoietin (r-HuEPO) can be effectively used to increase the volume of autologous blood obtained before surgery and to prevent the anemia caused by serial phlebotomy. Determining the optimal dose, route, and interval of administration of r-HuEPO is currently the object of ongoing investigations. PMID- 1615336 TI - The application of recombinant erythropoietin in anemic patients with cancer. AB - Recombinant human erythropoietin (r-HuEPO) has been shown to correct anemia and alleviate transfusion dependency in patients with end-stage renal disease, to ameliorate anemia and reduce transfusion requirements in anemic patients with acquired immunodeficiency syndrome, to correct anemia in patients with rheumatoid arthritis, and to facilitate predeposit autologous blood donation. Cancer is frequently complicated by anemia, and a survey of serum erythropoietin concentrations in anemic cancer patients showed inappropriately low concentrations for the degree of anemia. Initial clinical trials suggest that r HuEPO can correct the anemia associated with malignancy, but the exact role of the recombinant hormone in this situation remains to be defined. PMID- 1615337 TI - Use of recombinant human erythropoietin in the treatment of anemia in patients who have cancer. AB - Mild to moderate anemia associated with malignant disease can contribute to the overall morbidity in patients with cancer. Because this anemia has been linked to a blunted erythropoietin response, recombinant human erythropoietin (r-HuEPO) was assessed as a means to correct it and provide some degree of palliation. Three different patient populations were studied: one population not administered chemotherapy, a second population administered chemotherapy that did not include cisplatin, and a third population administered chemotherapy that included cisplatin. In all patient populations, r-HuEPO increased hematocrit values compare with placebo. In the two chemotherapy-treated populations, r-HuEPO decreased blood transfusion requirements after the first month of therapy. Patient-rated energy levels, ability to engage in daily activity, and overall quality of life improved in patients who responded to r-HuEPO therapy with an increase in hematocrit values of 6 percentage points or more. Thus, it appears that r-HuEPO may be a useful adjunct for palliation and treatment of anemia in patients with cancer. PMID- 1615338 TI - Changing patterns of care in the management of anemia. AB - There exists a potential for change in the approach to the management of the patient with chronic disease, specifically, the anemia of chronic disease (ACD). One of the components in the pathophysiology of ACD is inadequate erythropoietin response. Normally, as anemia develops, the erythropoietin level does not begin to increase until the hematocrit level decreases below 35%. However, the increase in the erythropoietin level is blunted in ACD. Increasing the hematocrit level by transfusion or recombinant human erythropoietin (r-HuEPO) treatment can subjectively and objectively improve the ACD patient's symptoms and performance. Although objective data in support of blood transfusions do exist, this treatment can carry risks of acute and chronic reactions, infection, and possibly immunosuppression. Treatment with r-HuEPO is a safer, nontransfusion means of increasing the hematocrit level of the patient with ACD symptoms. PMID- 1615339 TI - Biomodulation of chemotherapy-induced myelosuppression. AB - Growth factors, or cytokines, that have a broad spectrum of actions on lymphoid and myeloid cell lineages recently have been introduced into clinical practice. Erythropoietin, granulocyte-colony stimulating factor, and granulocyte-macrophage colony stimulating factor were the first to be introduced and to receive approval from the Food and Drug Administration. A number of interleukins and other cytokines presently are being developed. If a clinician is to use these potent biologicals appropriately, it is important that he or she understand the basic concepts of their biological actions and physiological effects. This article outlines features of production, cellular action, synergistic interactions, action on neoplastic cells, and clinical utility of these growth factors, all relating to their potential use in states of chemotherapy-induced myelosuppression. PMID- 1615340 TI - Control of G(0) phase of human bone marrow stem cells. PMID- 1615341 TI - T-cell depletion and allogeneic bone marrow transplantation. PMID- 1615342 TI - T-cell depletion in unrelated bone marrow transplantation. PMID- 1615343 TI - [Use of the terms "incidence" and "prevalence" in epidemiological studies]. PMID- 1615344 TI - [Perspectives of research and action in the field of infectious diseases in Mexico]. PMID- 1615345 TI - [Factors of Salmonella typhi virulence in relation to the development of new vaccines]. AB - Although many vaccines against typhoid fever have been developed, none have been adapted for their further application on developing countries. In order to get better vaccines, the virulence factors of both S. typhi and S. typhimurium have been studied. Thus, some protection assays have been made using surface antigens involved on virulence or using live attenuated vaccines of bacteria mutated on virulence genes. Here we present a brief review about virulence factors studied so far for the development of new vaccines. PMID- 1615346 TI - [Vaccines against Haemophilus influenzae B: present, past and future]. AB - Haemophilus influenzae type b (Hinb) is the main etiologic agent of severe pediatric illnesses, such as meningitis, epiglottitis and pneumonia. Countries most affected by this pathogen are localized in the American, European and African continents. While this organism was originally isolated 100 years ago, the first field trial using a whole killed vaccine was performed until 1959. Since then, further controlled clinical trials have mainly been conducted in the North American and European continents. Under appropriate safety and efficacy evaluation tests performed by the Federal Drug Administration Agency (FDA), five vaccines were licensed: one single and four conjugated preparations. Worldwide and regional epidemiologic data concerning serious diseases produced by this organism have shown their outstanding impact in the public health of developed countries. Unfortunately, in developing countries similar epidemiological indexes are lacking for lethal and disabling diseases, such as meningitis. In order to decrease high morbidity and mortality rates of this meningeal disease and its neurological sequelae, immunoprophylactic preventive measures have been recommended. Furthermore, some risk factors of this infant illness can also be reduced. New strategies regarding conjugate Hib-vaccines are reviewed. Finally, promising virulence factors or self Hib-structures for the production of vaccines are suggested, such as outer membrane proteins (OMP), lipooligosaccharides, fimbriae or pili. PMID- 1615347 TI - [Use of molecular biology in the epidemiological characterization of Neisseria gonorrhoeae]. AB - This paper describes current methods useful to define molecular markers from a collection of Neisseria gonorrhoeae strains. The procedures of auxotyping, serotyping and plasmid profiling led to the obtention of 10 auxotypes, 19 serotypes and five plasmid types (including beta-lactamase plasmids) among 41 gonococci studied. Twelve patterns of antimicrobial resistance were determined as well, through in vitro susceptibility testing by agar dilution. These tools in conjunction, offer the possibility to study gonorrhea in a dynamic fashion from an epidemiologic perspective. Furthermore, they have allowed us to establish a gonococcal reference laboratory in our institution. PMID- 1615348 TI - [Prevalence of cervicovaginal infections caused by Chlamydia trachomatis among female population of the city of Cuernavaca, Morelos]. AB - The chlamydiae are a genetically diverse group of bacteria with a unique intracellular development cycle. The spectrum of clinical manifestations of Chlamydia trachomatis infections in the female includes cervicitis, acute urethral syndrome, pelvic inflammatory disease, salpingitis and the risk of exposure of infants born through an infected birth canal who may develop inclusion conjunctivitis and/or pneumonia. In order to determine the prevalence of cervicovaginal infections caused by C. trachomatis in female population in Cuernavaca, Morelos, we studied 2,407 sexually active women from a suburban area. Genital specimens were collected from each woman and cultured in McCoy cell monolayers. Detection of the bacteria was done by staining with fluorescein conjugated monoclonal antibodies (Syva Microtrak, Palo Alto CA). 97 of them were culture-positive for C. trachomatis, with and overall prevalence of 4.02 per cent. The most important clinical symptom observed in 47 of the infected patients was an increased or altered vaginal discharge. PMID- 1615349 TI - [Epidemiology of rubella in Mexico]. AB - An analysis of the transmission dynamics of rubella in Mexico based upon notified cases during 1983-1990 is presented. It is observed, for the first time, that the force of infection in the age-group of 15-44 years old and the average age of the infection at the national level show a slight increase simultaneously. The theoretical estimates of the interepidemic period coincide with the observed ones. The annual proportion of susceptible individuals is practically constant during 1983-1990. The intrinsic reproductive rate of rubella at national level and for the different age-groups is assessed. The annual estimates of Ro are small and they are practically unchanged for all age-groups, excepting the group of 15-44 years. The herd immunity of rubella for the different age-groups is evaluated and it is concluded that the best strategy for preventing congenital rubella in Mexico is to continue with the no vaccination policy against rubella. Nonetheless, the continuous monitoring of this policy is necessary. PMID- 1615350 TI - [Seroepidemiology of rubella in Mexico: data and theory]. AB - The pattern of seropositivity of rubella obtained through the National Seroepidemiological Survey (NSS) of 1987-1988 is compared with the observed annual patterns of morbidity and with theoretical serological profiles based upon the age-distribution of cases. In spite of a lack of direct correspondence among the NSS results and the ones obtained from morbidity data, a relationship among the patterns and trends is observed. The theoretical methods used for inferring the proportion of seropositives as a function of age provide an inexpensive and fast alternative in order to monitor the current policy of no vaccination against rubella in Mexico. PMID- 1615351 TI - [Entamoeba histolytica: a standing threat]. AB - The importance and limitations of microscopic differential diagnosis of Entamoeba histolytica in asymptomatic carriers is reviewed. The possibility that some nonpathogenic strains of E. histolytica could be Entamoeba hartmanni is discussed. The imperative necessity to encourage research in epidemiology and diagnosis is emphasized. The need to know the prevalence in Mexico and distinguish E. histolytica from E. hartmanni is also discussed. This differential diagnosis is fundamental in the treatment of carriers and in epidemiological studies. Treatment must be directed only to acute and chronic patients and asymptomatic carries who prepare food. Appropriate drugs are still metronidazole and quinolines. PMID- 1615352 TI - [Infectious agents and autoimmune diseases]. AB - In this paper the molecular aspects of the relationships between infectious agents and autoimmune diseases, the mechanisms of immune response to infectious agents, and the more recent hypotheses regarding the cause of autoimmune diseases are discussed. The antigens are processed and selected by their immunogenicity, and presented by HLA molecules to the T cell receptor. These events initiate the immune response with the activation and proliferation of T-lymphocytes. Although there are several hypotheses regarding the cause of autoimmune diseases and too many findings against and in favor of them, there is still no conclusive data. All these hypothesis and findings are discussed in the context of the more recent advances. PMID- 1615353 TI - [Infectious diseases in the era of the global village]. AB - This paper discusses the situation of infectious diseases in an era of the global village. Emphasis is placed on three themes: 1) the blurring of geographical borders of infectious diseases; 2) the role of technology in the combat against infectious diseases, and 3) the need for international collaboration for the control of the main infectious problems. PMID- 1615354 TI - [The omnipresence of helminthiasis]. AB - This article presents a reflexion on the role of helminthic diseases in the world. Emphasis is made on the fact that in spite of its enormous diversity, helminthic parasites have similar epidemiologic behaviours and share high endemicity. Mathematical model design is crucial not only for a better understanding of their transmission mechanisms, but to evaluate different intervention strategies. Nonetheless, control of this serious endemic diseases will be achieved only through the joint effort of governments, funding agencies and researchers. PMID- 1615355 TI - [Transmission of cholera by flies. 1897]. PMID- 1615356 TI - Occupational lung disease. PMID- 1615357 TI - Rights and realities: a critical review of the accessibility of information on hazardous chemicals. AB - The importance of workers' right-to-know about current hazards in the workplace and the importance of notification about risks associated with past exposures would seem self-evident. Some of the methods for achieving the goal of an informed work force can be found in the existing right-to-know laws and notification programs. This article reviews right-to-know legislation and describes the current state of implementation of these regulations and some of the barriers that impair workers from receiving information and from being able to act to protect themselves. PMID- 1615358 TI - Pneumoconioses in the United States: highlights of surveillance data from NIOSH and other federal sources. PMID- 1615359 TI - Surveillance for lung disease. Quality assurance using computers and a team approach. AB - An occupational pulmonary surveillance program will detect the lung diseases that affect about 20% of the general population: asthma, chronic bronchitis, emphysema, restrictive disorders, and lung cancer. Annual spirometry testing and standardized respiratory questionnaires are useful components of all programs, but because many problems with spirometry testing and interpretation occur, a team approach is indicated. In order to minimize the false-positive rate, an expert in pulmonary surveillance should be included to help choose a good spirometry system, train technicians, monitor the quality of their work, and interpret the results. Interpretation of annual change in pulmonary function enhances the ability to detect lung disease early but requires knowledge of the test-retest reproducibility of the FEV1 of your own surveillance program. PMID- 1615360 TI - Inherited predisposition to lung cancer. AB - This chapter summarizes data from epidemiologic and animal model studies which demonstrate that an inherited predisposition influences the incidence of lung cancer. The authors review the cell biologic events that contribute to neoplastic transformation and the biologic processes that influence tumor progression. They describe how host mechanisms may limit the genesis and progression of tumors and discuss how information about mechanisms of carcinogenesis may be applied to estimating the risk of lung cancer in individuals exposed to environmental carcinogens. PMID- 1615361 TI - Pulmonary imaging techniques in the diagnosis of occupational interstitial lung disease. AB - The chest radiograph is extensively used in evaluating workers at risk for developing occupational lung disease. Other pulmonary imaging techniques used in conjunction with the initial chest radiograph include conventional computed tomography, high resolution computed tomography, and gallium scintigraphy. This chapter evaluates the use of these techniques and their appropriate applications in the pneumoconioses, hypersensitivity pneumonitis, berylliosis, and hard metal diseases. PMID- 1615362 TI - Environmental monitoring: correlating air measurements of substances with immune response. AB - In summary, data from animal models would suggest that air measurements of substances can be correlated with immune response, be it immunodepression or either of the two forms of immunostimulation-autoantibody formation or specific immunologic sensitization. However, became immunodepression and autoantibody formation are not specific for a given substance, and because they can be induced by a variety of other factors such as drugs and intercurrent viral infections, it would seem unlikely that correlations between air measurements and measurements of immunodepression or autoantibody formation could be very useful. In contrast, specific immunologic sensitization is a response that can only be induced by exposure to a specific agent. The major problem confronting investigators attempting to perform concentration-response studies in humans is accurate measurement of workplace exposures. If exposures could be reliably quantified, it is likely that concentration-response correlations could be determined for worker groups. This could prove useful for estimating exposure of groups based on aggregate immune response. It would be most useful, however, for determining threshold concentrations below which a very low proportion of workers--perhaps 1 in 100 or even 1 in 1000--would become sensitized. These threshold concentration levels of sensitizing substances could be used to develop permissible exposure levels in the workplace. Reducing workplace sensitization and diseases such as occupational asthma and hypersensitivity pneumonitis would be of obvious benefit to workers, management, government, and society at large. PMID- 1615363 TI - Water-related lung diseases. AB - A variety of water sources can act as reservoirs and vectors for contaminants associated with acute and chronic lung diseases. Inhalation of contaminated aerosols is the most important route of exposure leading to water-related lung disease. However, dermal absorption, disseminated marine-acquired wound infections, and ingestion or aspiration of water containing harmful contaminants have been associated with pulmonary disease as well. This article discusses these routes of infection and describes the infectious and noninfectious lung diseases associated with exposure to water. PMID- 1615364 TI - Acquired airway hyperresponsiveness from nonimmunogenic irritant exposure. AB - The question of whether nonallergic airway hyperresponsiveness is an acquired or an inherent phenomenon is important in the understanding of occupational lung disease, as it has implications for the management and prevention of occupational disease. This chapter reviews the evidence suggesting that airway hyperresponsiveness may be acquired as a result of exposure to irritants in the workplace. PMID- 1615365 TI - Isocyanates and lung disease: experimental approaches to molecular mechanisms. AB - Isocyanates are reactive compounds that have commercial applications in the synthesis of a variety of products, including paints, coatings, elastomers, and foams. The correlation between isocyanates and a spectrum of respiratory disease has been established, primarily at the clinical level. The focus of this article is to bridge the gap of understanding from clinical symptoms to molecular reactivity, with emphasis on experimental approaches that serve to complement clinical and epidemiologic data. PMID- 1615366 TI - Occupational and environmental respiratory diseases: a medicolegal primer for physicians. AB - This article is an introduction to medicine and the law with specific reference to occupational and environmental respiratory diseases. It provides an initial orientation for practicing physicians and includes basic definitions, practices and procedures, and helpful hints. Basic information about impairment and disability evaluations are reviewed. PMID- 1615367 TI - Don't just "do spirometry"--closing the loop in workplace spirometry programs. AB - The authors acknowledge that surveillance is a word that often causes eyes to glaze over and recognize that spirometry is often a casualty of a routine approach to surveillance. This article describes how to use spirometry as an active part of an on-site workplace occupational health program whose emphasis is avoiding trouble by knowing where and how to look for signs of occupational lung disease. PMID- 1615368 TI - Central diabetes insipidus resulting from a nonneoplastic tiny mass lesion localized in the neurohypophyseal system. AB - With the advent of magnetic resonance imaging (MRI), the neurohypophyseal system can be clearly delineated and its functional integrity can be predicted. The authors describe seven cases of central diabetes insipidus (DI) that occurred spontaneously. MRI revealed that the normal hyperintensity of the pituitary posterior lobe, which has been thought to be the neurosecretory material containing antidiuretic hormone, was absent in all cases. In addition, enlargement of a part of the neurohypophyseal system was recognized in five of seven cases on MRI. Three of the five patients with enlargement of a part of the neurohypophyseal tract underwent biopsy and were demonstrated to have chronic inflammation of the neurohypophyseal system. It was demonstrated that the enlarged parts of the neurohypophyseal system had shrunk either spontaneously or after the biopsy in four of the five cases. All patients are alive and have not experienced progression or remission of the disease. This study indicates that some cases of idiopathic DI result from a tiny mass lesion, usually nonneoplastic, localized in the neurohypophyseal system. PMID- 1615369 TI - Primary tumors of the cervical spine: surgical experience with 38 cases. AB - Thirty-eight primary tumors of the cervical spine were operated on in the Section of Neurosurgery, Department of Neurological Sciences, "La Sapienza" University of Rome between 1954 and 1988. Of these, 23 were malignant and 15 benign. The aims of surgical treatment in every case were tumor removal, decompression of the spinal cord, and conservation or restoration of vertebral stability. In no case was surgery confined to biopsy. Surgical stabilization was performed in 12 patients. Bone fusion was obtained with autologous bone (iliac crest, fibula) in benign tumors, whereas synthetic material (acrylic and metal) was used in malignant tumors. Past experience and greater awareness of the concrete possibilities of treating these tumors have led us to evolve the following strategy: 1. For aggressive benign tumors (osteoblastoma, giant cell tumors) and for malignancies in patients with fair life expectancy (solitary myeloma, chordoma): radical removal. 2. For benign tumors with low neoplastic potential and for malignant tumors in patients with poor life expectancy: conservative removal. Long-term results were gratifying in all benign lesions and low-grade malignancies even though two patients with chordomas needed reoperations. Sarcomas had relatively poor results. PMID- 1615370 TI - Direct surgery for giant aneurysm exhibiting progressive enlargement after intraaneurysmal balloon embolization. AB - A case of giant intracranial carotid artery aneurysm exhibiting progressive enlargement after incomplete intraaneurysmal balloon embolization is presented. The patient was successfully treated by the trapping and decompression of the aneurysm with a superficial temporal artery-middle cerebral artery anastomosis. The thrombus surrounding the intraluminal balloons was very soft and poorly organized. Either direct surgery with extracranial-intracranial arterial bypass or complete intravascular surgery should be performed for giant aneurysms when direct clipping is impossible. PMID- 1615371 TI - Primary solitary intracranial melanoma: case report and review of the literature. AB - Among CNS tumors, intracranial melanomas represent a subject of interest for neurooncologists and neurosurgeons because clinical and radiological patterns of these tumors can mimic the presence of meningiomas, and in spite of their malignant behavior they can be satisfactorily treated. In the present report we describe a new case of primary intracranial melanoma that displayed some radiological features of meningioma; we review the clinical features of 80 previously well-documented cases. The importance of neuroradiological and histochemical (S-100 protein, antimelanin antibodies, proliferating cell nuclear antigen staining) methods and of flow cytometry in helping with histopathological examination is stressed. Review of the clinical histories demonstrates that surgical excision is recommended in most cases, depending on tumor location, and that if total removal is performed, long-term disease-free periods can be attained. PMID- 1615372 TI - Periventricular neurocytoma: a pathological entity. AB - Three cases of periventricular neurocytomas are presented. All patients had a large but well-circumscribed, hyperdense tumor with insignificant contrast enhancement in the lateral and third ventricle, causing hydrocephalus. Calcification was present in one patient. Angiography revealed a blush tumor enhancement in two cases. Surgical removal was complete in two patients and incomplete in one. Light microscopy showed a cell pattern that resembled either ependymoma or oligodendroglioma. However, in all cases the tumor was confirmed to be a neurocytoma by immunocytochemical analysis that showed reactivity for synaptophysin and/or neuron-specific enolase in a high percentage of neoplastic cells. With respect to the literature it is concluded that neurocytomas represent an individual pathological entity of supratentorial midline tumors. Complete surgical removal without irradiation is the recommended treatment. PMID- 1615374 TI - Occult spinal pseudomeningocele following a trivial injury successfully treated with a lumboperitoneal shunt: a case report. AB - A patient with a traumatic occult spinal pseudomeningocele is presented. The possible etiology and the use of a lumboperitoneal shunt in this situation are discussed. PMID- 1615373 TI - Posterior inferior cerebellar artery (PICA) aneurysm presenting with SAH and contralateral crural monoparesis: a case report. AB - A patient with contralateral monoparesis of the leg due to subarachnoid hemorrhage (SAH) from an aneurysm of the first posterior inferior cerebellar artery (PICA) segment is reported. The monoparesis may well be associated with the close anatomical relationships between the site of the aneurysm and the PICA blood supply of the corticospinal fibers to the contralateral leg. PMID- 1615375 TI - Endovascular coil embolization of a recurrent giant internal carotid artery aneurysm via the posterior communicating artery after cervical carotid ligation: case report. AB - The case of a 29-year-old man with a giant fusiform aneurysm of the left internal carotid artery (ICA) is presented. The aneurysm, treated by cervical ICA ligation and extracranial-intracranial bypass, recurred 4 years later owing to recruitment of the posterior communicating artery (PCoA). Because of the previous bypass surgery a direct surgical approach was excluded. After an initial failure with balloon embolization, the aneurysm was embolized successfully with occlusive platinum microcoils through the microcatheter navigated into the aneurysm via the enlarged PCoA. Endovascular coil embolization may be useful in the treatment of cerebral aneurysms not amenable to direct surgery or balloon embolization. PMID- 1615376 TI - Symptomatic cerebral vasospasm after intraventricular hemorrhage from ruptured arteriovenous malformation. AB - We present a rare case showing symptomatic vasospasm after intraventricular hemorrhage from a ruptured arteriovenous malformation. No significant subarachnoid hemorrhage in the basal cisterns was observed on computed tomography in the entire course of illness. Although most cases showing vasospasm are associated with the deposition of blood in the basal cisterns, this case suggests the possibility of some other important factor in causing the subsequent development of vasospasm. PMID- 1615377 TI - Cranial fasciitis of childhood: a case report. AB - Cranial fasciitis of childhood is very rare, only 17 cases having been reported in the literature. We report an additional case of this rare disease. The patient was a 5-year-old boy who complained of left exophthalmos and double vision. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a large epidural mass in the left frontal region that had invaded into the underlying anterior skull base. The tumor showed homogeneous, low density with nonhomogeneous contrast enhancement on the CT scans, and low intensity on the T1 weighted and high intensity on the T2-weighted MRI images. A whitish-pink, elastic, hard tumor was revealed in the epidural space in the left anterior cranial fossa, which was totally excised with curettage of the affected anterior skull base. The origin of the tumor was suspected to be the fibrous connective tissue of the sphenofrontal suture. The histological diagnosis was that of cranial fasciitis. There was no evidence of recurrence 1 year postoperatively. PMID- 1615378 TI - Nicardipine in the prevention of spasm-induced neurological deficits after subarachnoid hemorrhage: a dose-ranging study. AB - The tolerability of four doses of intravenous nicardipine (0.03, 0.08, 0.11, and 0.15 mg/kg/h) was assessed in this randomized multicenter, parallel-group study. Fifty-two patients with Hunt and Hess grade I-III aneurysmal subarachnoid hemorrhage were treated with intravenous nicardipine beginning within 4 days of bleeding, for a mean duration of 12.6 days; this treatment was followed by administration of oral nicardipine 90-120 mg until day 30. Hypotension was the main side effect, and it occurred only in the two groups that received the highest doses. However, it was possible to continue nicardipine in all cases at lower doses or even without modification, and hypotension was never responsible for any deleterious clinical effect. PMID- 1615379 TI - Can laser angioplasty replace carotid endarterectomy in the management of nonstenotic atheromatous disease of the carotid bifurcation? PMID- 1615380 TI - Discovery of the arachnoid membrane. PMID- 1615382 TI - [Medical technology in primary school]. PMID- 1615381 TI - [History--a life in the forefront. Interview by Ole Sohn]. PMID- 1615383 TI - [ICN--solidarity with colleagues in Ghana]. PMID- 1615384 TI - [Education. Philosophy for nurses]. PMID- 1615385 TI - [Work environment. Work Inspection wants to inspect all hospitals]. PMID- 1615386 TI - [AIDS--Noah's Ark]. PMID- 1615388 TI - [Outpatient childbirth. Lack of milk]. PMID- 1615387 TI - [Outpatient childbirth. Restraint with success]. PMID- 1615389 TI - [Health policy--pictures of the future. Interview by Kirsten Bjornsson]. PMID- 1615390 TI - [Taxes--nurses' 1991 income tax returns]. PMID- 1615391 TI - [Needed--continuing education]. PMID- 1615392 TI - [Home care nursing--challenge and frustration]. PMID- 1615393 TI - [Team work. Health visitors are needed when children are hospitalized]. PMID- 1615394 TI - [Nutrition. Standard diet--a bad idea]. PMID- 1615395 TI - [Nursing home--fellowship group as a form of nursing]. PMID- 1615396 TI - [Outpatient--the form of surgery for the future]. PMID- 1615397 TI - [Clinical nursing. The pouch-free system]. PMID- 1615398 TI - [Spiritual care]. PMID- 1615399 TI - [Executive Board--afraid at work]. PMID- 1615400 TI - [Executive Board--standardization is not included in assignments]. PMID- 1615401 TI - [Kuwait--new professional horizons]. PMID- 1615402 TI - [Physician's on-call roster. Children, trifles and drug addicts]. PMID- 1615403 TI - [Physician's on-call roster. A pampered generation]. PMID- 1615404 TI - [Physician's on-call roster. The psychological support bandage]. PMID- 1615405 TI - [Physician's on-call roster. Shorter on-call hours, more patients]. PMID- 1615406 TI - [Physician's on-call roster. The new arrangement]. PMID- 1615407 TI - [Good and bad working days]. PMID- 1615409 TI - [Romania--Danish behind the new education system]. PMID- 1615408 TI - [Education on the spot]. PMID- 1615410 TI - [Professional nursing guidelines. Bridge between theory and practice]. PMID- 1615411 TI - [Physician's on-call roster and nurses]. PMID- 1615412 TI - [Physician's on-call roster. Weekend on-call in medical practice]. PMID- 1615413 TI - [Physician's on-call roster. Entire family involved in on-call activities]. PMID- 1615414 TI - [Everyday with diagnosis]. PMID- 1615415 TI - [Documentation--support enthusiastic minds]. PMID- 1615416 TI - [EEC will influence health system]. PMID- 1615417 TI - [Report on health legislation--shortages and goal-setting]. PMID- 1615418 TI - [France--sit-in cleared away]. PMID- 1615419 TI - [France--5 percent organized]. PMID- 1615420 TI - [France--we will create a new professional organization]. PMID- 1615421 TI - Comments on "Target tissue specificity of retinoic acid-induced stress proteins and malformations in mice". PMID- 1615422 TI - The "maternal arterial space" in the center of rats' placenta may be venous, not arterial. PMID- 1615423 TI - The interaction between dysmorphology and epidemiology: methodologic issues of lumping and splitting. PMID- 1615424 TI - Distal phocomelia of the forearm in a thirteenth-century skeleton from Poland. AB - The skeleton of a 35- to 40-year-old male (A.D. 1250 to 1300) with distal phocomelia (intercalary transverse) of the right forearm and severe (90-100 degrees) right-sided scoliosis is examined. Congenital malformation of the the right forearm resulted in absence of the radius and ulna, and attachment of the upper arm and hand to the trunk. Lesser abnormalities consist of a-hypoplastic right scapula and misshapened ribs and sternum. This rare deformity reflects the variability and antiquity of congenital malformations of the upper limb. PMID- 1615425 TI - Cardiovascular anomalies in chick embryos produced by bis-diamine in dimethylsulfoxide. AB - N,N'-bis(dichloroacetyl)-1,8-octamethylenediamine(bis-diamin e) (100 micrograms) dissolved in dimethylsulfoxide (DMSO) was administered to early developing chick embryos (Hamburger-Hamilton stage 9-21) in order to clarify the teratogenic effects on the cardiovascular system and to determine whether bis-diamine interferes with the migration of neural crest cells. Of 346 cases, 154 (44.5%) survived. The incidence of cardiovascular anomalies was 149 out of 154 cases (96.8%). Infundibular ventricular septal defect, double outlet right ventricle, and persistent truncus arteriosus were the primary cardiac anomalies observed in this study. A high percentage of these anomalies were accompanied by hypoplasia of the right 6th aortic arch artery and persistent left 4th aortic arch artery. Particularly, administration of bis-diamine to chick embryos at stage 13 resulted in a high incidence of persistent truncus arteriosus (64.3%). Bis-diamine has been suspected to inhibiting the migration of neural crest cells. However, neural crest cells were observed in the tunica media of the great arteries and the truncal valves of persistent truncus arteriosus produced by bis-diamine in chimeric embryos at stage 13. Morphological changes such as cell death were not observed. PMID- 1615426 TI - Effects of 4-hydroperoxycyclophosphamide (4-OOH-CP) and 4 hydroperoxydechlorocyclophosphamide (4-OOH-deCICP) on the cell cycle of post implantation rat embryos. AB - In this study, we used preactivated forms of cyclophosphamide (CP) and dechlorocyclophosphamide (deClCP) to examine the effects of phosphoramide mustard (PM) and acrolein, respectively, on the cell cycle of postimplantation rat embryos. The percentage distribution of cells in the G1/G0, S, and G2/M phases of the cell cycle was determined by flow-cytometric analysis. At embryotoxic concentrations, 4-OOH-CP (PM) induced major cell cycle perturbations whereas 4 OOH-deClCP (acrolein) caused no major perturbation of the cell cycle. These data support the hypothesis that the mechanism of the embryotoxic action of PM involves alkylation of DNA, whereas the mechanism of action of acrolein does not. The primary effect of PM on the cell cycle was an initial delay in the S phase followed by a G2/M arrest. At low embryotoxic concentrations of 4-OOH-CP, there was apparent reversal of the G2/M arrest; at higher embryotoxic concentrations there was little recovery from the G2/M arrest. The high level of cell death found at higher drug concentrations suggests that prolonged G2/M arrest leads to cell death. Using radiolabeled CP and cell sorting, it was determined that PM predominantly alkylated DNA in the S phase of the cell cycle. Overall, the data from this study support the hypothesis that DNA cross-links, induced by the alkylation of DNA by PM, induce cell cycle perturbations. Furthermore, these cell cycle alterations may be one of the early steps in the mechanism leading to the embryotoxicity of PM. PMID- 1615428 TI - The use of dysmorphology in birth defects epidemiology. AB - Most human teratogens have been identified by the clinical recognition of characteristic patterns of congenital anomalies among children whose mothers were exposed to a particular agent during pregnancy. Although this dysmorphologic method has been valuable, it is criticized because it is not easily amenable to statistical evaluation. Conventional birth defects epidemiological studies are designed to permit rigorous statistical assessment, but such investigations usually classify congenital anomalies without adequate consideration of their known etiological heterogeneity. It is possible to combine the best aspects of these two approaches to identifying human teratogens in a "dysmorphologic case/control study." Instead of including all available cases with a given defect, only individuals having the anomaly in the context of a multiple congenital anomaly pattern without a recognizable cause would be selected for inclusion among the case group. The frequency of exposure to the putative teratogen would be determined among these selected cases and among appropriately chosen controls; conventional statistical analysis would then be performed. Although this design reduces the size of the case group compared to a conventional case/control study, the statistical power is unchanged or increased. In addition, biological plausibility is increased by concentrating upon a group of cases that is more likely to have a teratogenic cause. PMID- 1615427 TI - Retinamides: hydrolytic conversion of retinoylglycine to retinoic acid in pregnant mice contributes to teratogenicity. AB - Retinamides are prominent among synthetic vitamin A derivatives (retinoids) which can prevent or reduce the incidence of certain carcinogen-induced neoplasms in animals. They also possess lower toxicity toward adult and developmental systems than natural retinoids, presumably because of the presence of an amide endgroup which resists ready hydrolysis. In this investigation, we compared the developmental toxicities in mice of N-(4-hydroxyphenyl)retinamide(4-HPR), N ethylretinamide (ER) and two retinoylamino acids, N-(all-trans-retinoyl)glycine (RG) and N-(all-trans-retinoyl)-DL-leucine (RL), which are formed from retinoic acid and the alpha-amino acids; RG and RL were shown in a previous study to differ from each other and from retinoic acid in certain toxicity bioassays. We found that while 4-HPR, ER, and RL were only minimally embryotoxic, RG was uniquely active as a teratogen with potency equivalent to that of retinol, the precursor of retinoic acid. Since binding to cytoplasmic proteins and nuclear receptors is a function of the presence of an acidic endgroup in the retinoid molecule, we investigated if RG given to pregnant mice was converted to retinoic acid (RA) and if teratologically significant amounts were detectable in the embryo. A single 100 mg/kg dose of RG in oil vehicle was given orally to ICR mice on day 11 of gestation (plug day = day 0). Extraction and quantification by HPLC of the retinoids in the maternal plasma and in whole embryos were performed at hourly intervals for the first 10 h after dosing and at 26 h. RG was absorbed rapidly reaching peak levels in the maternal plasma at 1 h after the dose and maintained a level of 15 micrograms/mL for up to 4 h, before starting a decline. RG also transferred to the embryo reaching peak levels greater than 0.75 micrograms/g wet weight between 2 and 4 h after the dose. All-trans RA was detected in the maternal plasma and the embryo at 1 h after the dose, reaching peak levels at 2 h in both compartments (0.43 micrograms/mL or g), before starting a decline. Small quantities of 13-cis RG (a contaminant in the original solution comprising 2-3% by weight) and 13-cis RA were also detected in both compartments, but their amounts in the embryo were considered insufficient to contribute to teratogenicity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1615429 TI - The role of the visceral yolk sac in hyperglycemia-induced embryopathies in mouse embryos in vitro. AB - The adverse developmental effects of hyperglycemia to rodent embryos have been shown using whole embryo culture. Although, a mechanism by which hyperglycemia induced effects occur is unknown, recent work has focused on the visceral yolk sac as a potential target tissue. Therefore, we have evaluated the developmental effects of hyperglycemia in early head fold stage mouse embryos in vitro and assessed the histiotrophic function of the visceral yolk sac. As has been previously shown in rodents, hyperglycemia produced neural tube closure defects in a concentration dependent manner at 33, 50, and 67 mM glucose using a 44 h exposure period. However, exposure times between 6 and 12 h were sufficient to alter embryonic development when the glucose concentration was 50 or 67 mM. In contrast, early somite stage embryos (4-6 somite stage) appear to be less sensitive to dysmorphogenesis and a 48 h exposure to 67 mM glucose but not 33 or 50 mM also produced neural tube defects. Hyperglycemia (67 mM) did not alter the uptake of 35S-methionine and 35S-cysteine-labeled hemoglobin (35S-Hb) in the visceral yolk sac (VYS) in early headfold staged embryos. However, the accumulation of 35S in the embryo was reduced by 16-18% at glucose concentrations of 50 or 67 mM during the last 12 h of a 44 h exposure period. No effect on VYS uptake or embryonic accumulation of 35S-labeled products was observed at shorter exposure periods (12-24 and 24-36 h).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615430 TI - Maternal methionine supplementation promotes the remediation of axial defects in Axd mouse neural tube mutants. AB - The Axd (axial defects) mouse model system (Essien et al., Teratology 42:183-194, '90) is characterized by a dominant mutation which causes posterior open neural tube defects (NTD) and a variety of tail anomalies (curly tails, or CT). Repeated backcrosses to BALB/cByJ mice have resulted in a 50% increase in Axd penetrance among neonates of heterozygous matings and loss of a correlation with maternal tail phenotype. Analysis of D12-D18 embryos from Axd/+ x Axd/+ matings indicates that soft tissues can superficially heal over some lesions from open NTD and that some curly tails can straighten (macroscopically) as gestation proceeds. Similarly, in embryos of Axd/+ x BALB crosses, there is remediation of approximately 33% of the tail flexion defects by birth. Numerous studies show that maternal nutritional status can affect the development of the neural tube and related axial structures. One nutrient of special interest is methionine, which is required for neurulation in cultured rat embryos (Coelho et al., J. Nutr. 119:1716, '89). Thus, the major question addressed by this study was whether supplemental methionine administered to Axd/+ dams crossed to Axd/+ males would alter the prenatal expression of the gene. When given IP (70 mg/kg) on D8 and D9, methionine resulted in a 41% reduction (from 29% to 17%) in the incidence of NTD in D 14 embryos (P less than 0.01). PMID- 1615431 TI - Morphological changes in long bone development in fetal akinesia deformation sequence: an experimental study in curarized rat fetuses. AB - In order to investigate the transverse growth of the long bones during intrauterine development in the fetal akinesia deformation sequence (FADS), we studied curarized rat fetuses. Curarization was performed by daily subcutaneous administration of D-Tubocurarine from day 17 of gestation until term. Experimental fetuses were compared with a sham-operated control group. The total area and perimeter, the absolute and relative amount of periosteum and bone trabeculae, the major and minor axes, and the elongation factor were measured from histological cross-sections of the femoral metaphysis and diaphysis using an IBAS 1 image analysis system. Curarized rat fetuses showed growth retardation, a short umbilical cord, and multiple articular contractures, a phenotype consistent with FADS. Alterations in femoral shape and transverse growth that affected the diaphysis were noted in these fetuses. These included a decrease of total cross section area and reduction of the absolute and relative amounts of bone trabeculae with marked thinning of the periosteum. Femoral cross-sections was rounder than controls. These results evidenced an impairment of the membraneous (periosteal) ossification of long bones produced by immobilization and/or decrease of muscular strength, and support our previous clinical findings of bone hypoplasia and osteopenia in FADS. PMID- 1615432 TI - Inositol deficiency increases the susceptibility to neural tube defects of genetically predisposed (curly tail) mouse embryos in vitro. AB - Curly tail (ct/ct) mouse embryos, which have a genetic predisposition for neural tube defects (NTD), were grown in culture from the 2-5 somite stage, before the initiation of neurulation, up to the 22-24 somite stage, when closure of the anterior neural tube is normally complete. The embryos were cultured in whole rat serum or in extensively dialysed serum supplemented with glucose, amino acids, and vitamins, with inositol omitted or added at concentrations of 2, 10, 20, and 50 mg/l. Two strains were used as controls; CBA mice, which are related to curly tails, and an unrelated PO stock. It was found that ct/ct embryos were particularly sensitive to inositol deficiency; both they and the CBA embryos showed a similar high incidence of cranial NTD after culture in inositol deficient medium (12/17 and 11/18, respectively). Furthermore, the lowest dose of inositol had no effect on the frequency of head defects in ct/ct mice, though it halved the incidence in CBA embryos. With higher inositol concentrations, the majority of ct/ct embryos completed head closure normally, and their development was generally similar to that obtained in whole serum. PO embryos showed a lower proportion (5/19) of cranial NTD in the inositol deficient medium than the other two strains, and this was further reduced by even the lowest inositol dose. PMID- 1615433 TI - Could a national health system really be worse? PMID- 1615434 TI - Insurance plan for Texas physicians makes major changes in HIV/AIDS coverages. PMID- 1615435 TI - Here's help in understanding Medicare's new claim form. PMID- 1615436 TI - Important dates loom for compliance with CLIA regulations. PMID- 1615437 TI - Rio Grande Valley physicians call for tort reform. PMID- 1615438 TI - New health reform plan maintains free-market system. PMID- 1615439 TI - Researchers seek new class of AIDS drugs. PMID- 1615440 TI - Student loan program revisions stall in Congress. PMID- 1615442 TI - Physicians have a place to take concerns under new UR rules. PMID- 1615441 TI - Training employees required under OSHA regulations. PMID- 1615443 TI - Neglecting informed consent is fuel for malpractice suits. PMID- 1615444 TI - TB waging attack on HIV-positive patients and jail inmates. PMID- 1615445 TI - Doctors join "Way Cool" adolescent health program. PMID- 1615446 TI - Reducing teen pregnancy rates is goal of summit. PMID- 1615447 TI - Agenda on AIDS. PMID- 1615448 TI - The cost of cancer in Texas. AB - Direct and indirect costs of cancer for Texas are estimated for 1988 and are compared to costs for 1980. The distribution of these costs by age group and type of cancer is presented and discussed. Conceptual and methodological issues underlying the estimates are explained to assist the reader in interpretation. The authors conclude that future collection of more specific data at the state level would greatly assist policymakers dealing with cancer issues. PMID- 1615449 TI - Selective posterior rhizotomy to treat spasticity associated with cerebral palsy: a critical review. AB - Selective posterior rhizotomy for the treatment of spasticity has become a widely used procedure. The historical evolution of this procedure is reviewed with an emphasis on the physiological basis for the procedure. The proper screening and selection criteria, perioperative management, operative technique, and postoperative therapy are discussed. Results from a series of 25 patients are reviewed. Ten of these patients were operated on for a goal of improved ease in caretaking and this was achieved. In seven patients, the goal was to improve independent functioning (ambulation was not considered possible) and this was achieved. Eight patients underwent the procedure to improve ambulation and this was achieved. PMID- 1615450 TI - "If the government would just leave us alone...". PMID- 1615452 TI - No easy solution for homicide rate. PMID- 1615451 TI - Physician defends rural health clinics. PMID- 1615453 TI - [Common cold: diagnostic steps? Antibiotics?]. AB - The common cold is caused by more than 100 virus types. However, the clinical manifestation is always similar with rhinorrhea, stuffiness, sneezing, pharyngitis, laryngitis and cough. The local inflammatory reactions are not due to the presence of virus but caused by locally produced inflammatory mediators. Bacterial superinfections may cause otitis or sinusitis. Bacterial nasopharyngitis has been described in children. This entity possibly exists also in adults. Traditional viral cultures are rarely positive and are not recommended in the daily routine. In children, antigen detection for adenovirus, respiratory syncytial virus, parainfluenza and influenza virus are recommended to confirm the viral etiology or for epidemiological surveillance. The presence of group-A streptococci must be proven by culture or antigen detection before treatment with penicillin. Antiviral treatment is limited to interferon or ribavirin. New antiviral substances are in development. Today, treatment of common cold is limited to symptomatic measures, and antibiotic treatment is not justified. PMID- 1615454 TI - [Infectious sinusitis and otitis]. AB - Insight into the pathogenesis and knowledge of the microbial flora provide the basis for the treatment of sinus and ear infections. Reduced oxygen tension and impaired mucociliary transport are important factors that influence the pathogenesis of both acute and chronic sinusitis and otitis. Therefore, topical decongestion and antibiotic regimens belong to the main therapeutic principles. The choice of an antibiotic for treatment of acute infections is usually empiric; however, in chronic and recurrent infections identification of the microbiology by fluid aspiration from the sinus or middle ear is desirable before long-term antibiotic therapy is initiated. It is also important to recognize underlying predisposing conditions such as nasal polyps, anatomic deformities or tooth abscesses which should be corrected to prevent further recurrences. External otitis is a painful condition seen most frequently in the swimming season (swimmer's ear) and is often associated with the use of cotton swabs. Repeated removal of debris from of the external canal and ototopical antibiotics are mostly successful; however, in severe cases like in necrotizing external otitis antibiotic therapy is indicated. PMID- 1615455 TI - [Group A streptococci 1992--a challenge for general practice, hospital and research]. AB - Group A streptococci continue to frequently cause a wide array of infectious diseases. Prompt and reliable diagnosis of such patients and their adequate management are often complex and require substantial degree of both knowledge and suspicion. Modern aspects concerning acute streptococcal pharyngitis, invasive infections, and rheumatic fever represent important challenges for medical doctors working in private praxis, hospital and research. Major achievements in better understanding streptococcal infection include the complex pathogenicity of M-proteins, the perplexing results of uncritically performed throat cultures, the questionable therapeutic dominance of penicillin, and the prospect for active immunization. These changes certainly imply relevant adaption in managing group A streptococcal infections. PMID- 1615456 TI - [Acute and chronic bronchitis]. AB - Acute bronchitis and exacerbations of chronic bronchitis are important problems in clinical practice. Acute bronchitis is frequently caused by viruses, and rarely by Mycoplasma or Chlamydia pneumoniae. Antimicrobial therapy is generally not indicated. The causes of exacerbations in patients with chronic bronchitis are often not clear. Beside environmental irritants and hypersensitivity with acute bronchospasm, viral infections are important. The role of bacterial infections is not established. Nevertheless, early antibiotic treatment seems to be beneficial, particularly in reducing the incidence of respiratory deterioration, and therefore decreasing cost and morbidity. PMID- 1615457 TI - [Pneumonia: etiologic diagnosis and therapy in general practice]. AB - The majority of community-acquired pneumonias are not hospitalized, have a good prognosis and a low mortality rate. In the nonimmunocompromised adult patient, pneumonias are caused by a broad array of microorganisms of which the so-called 'atypical' agents (mycoplasma, chlamydiae, viruses) are as frequently found as classical bacteria such as pneumococci and haemophilus. Generally, the mode of acquisition and the clinical picture will not allow to deduct the etiology with certainty, and the laboratory results are often nonconclusive (sputum examination) or delayed (serology). Empirical therapy should be initiated based on epidemiological grounds and on the characteristics of the patient. For patients without underlying conditions, immunosuppression or advanced age, a macrolide (erythromycin or a new macrolide) appears to constitute a good choice because of its broad spectrum of activity, comprising the classical bacterial agents of pneumonia, mycoplasma, chlamydiae, and legionella. PMID- 1615458 TI - [Urinary tract infections in general practice]. AB - Urinary tract infections are a frequent problem in ambulatory practices. According to the localization of the infection and to complicating factors we differentiate between various syndromes with different clinical presentations. Relevant diagnostic criteria are a bacteriuria of greater than or equal to 100 organisms par millilitre or a pyuria of greater than or equal to 5 leukocytes per high power field. For acute cystitis, a treatment for three days is recommended. Cotrimoxazole or quinolones are effective drugs, which are more and more recommended for the treatment of acute pyelonephritis, too. PMID- 1615459 TI - [Bacterial gastrointestinal infections: acute gastroenteritis]. AB - The diagnosis of bacterial gastrointestinal infections is based on anamnesis, clinical signs and simple examinations of feces (fecal leucocytes, occult blood). Thereby it can be decided, whether a microbial identification by culture or an antibiotic therapy is indicated. In case of noninvasive infections mediated by enterotoxins, an oral substitution of liquid will suffice. An antibiotic therapy is indicated in case of severe, febrile dysentery, shigellosis, cholera, typhoid fever as well as severe infections by salmonella and clostridium difficile. PMID- 1615460 TI - [Localized bacterial skin infections and dermatologic manifestations of systemic infections]. AB - Localized bacterial skin infections are frequent. In furunculosis, a local treatment is usually sufficient. In case of frequent recurrence a possible staphylococcus aureus colonization should be looked for and eliminated. Erysipela is treated by systemic antibiotics in order to avoid complications such as streptococcal gangrena or parainfectious glomerulonephritis. Anaerobic cellulitis and gas gangrena are postoperative or posttraumatic infections of the soft tissues which require a combined surgical and antibiotic treatment. Systemic infections may be recognized by characteristic skin lesions. These skin lesions are the consequence of bacterial emboli, vasculitis, intravascular coagulation or toxins, respectively. Examples for such manifestations are lesions in endocarditis, purpura fulminans, ekthyma gangrenosum, disseminated candidemia and toxic shock syndrome. PMID- 1615461 TI - [Suspected Lyme borreliosis: how to diagnose, whom to treat?]. AB - Lyme Borreliosis is diagnosed or presumed primarily on a clinical basis. Serological tests may help to increase the diagnostic certainty. Type and duration of antibiotic therapy depend on the stage of the disease. PMID- 1615462 TI - [Fever without a recognizable cause in general practice: what should be done?]. AB - Fever is one of the most common presenting symptoms for consultation in general practice. For the vast majority of cases, a specific cause is never found, and the fever disappears spontaneously. We present an algorithm for the management of a febrile adult patient with the aim to help recognize early a potentially dangerous infection and to avoid unjustified blind antibiotic therapy. PMID- 1615463 TI - The amount of plasminogen, tissue-type plasminogen activator and plasminogen activator inhibitor type 1 in human thrombi and the relation to ex-vivo lysibility. AB - Thrombolytic therapy successfully reopens obstructed blood vessels in the majority of cases. However, it is not known why a substantial amount of thrombi are resistant to lysis by a fibrinolytic agent. In vitro studies have demonstrated that tissue-type plasminogen activator (t-PA) and plasminogen incorporated in the clot (during formation) increase lysibility. To test whether lysibility of in vivo formed human thrombi is related to their composition, we studied 25 venous thrombi obtained at autopsy and 21 arterial thrombi obtained during embolectomy. Plasminogen activator inhibitor-1 (PAI-1) antigen was measured in a phosphate-buffered saline (PBS) extract of each thrombus; t-PA antigen and plasminogen antigen were determined in a 6 M urea extract of the thrombus, representing bound proteins. Lysibility was measured as weight reduction during 8 h of incubation in PBS containing streptokinase (SK) 100 U/ml, corrected for spontaneous lysis, reflected by weight loss in PBS without SK. In addition, lysibility in SK was compared with lysibility in urokinase (UK) 100 U/ml and in t-PA 200 U/ml. Spontaneous lysis amounted to 29 +/- 5% (mean +/- SEM) and 33 +/- 5% in venous and arterial thrombi, respectively, and inversely correlated with the PAI-1 content of thrombi (r = -0.43, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615464 TI - Effect of plasminogen activator inhibitor-1 on tissue-type plasminogen activator induced fibrinolysis. AB - The effect of fibrin on the interaction of human recombinant single-chain tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) was studied in normal rabbit plasma and in plasma with high levels of native PAI-1. t PA was added to diluted plasma containing calcium (10 mM) and 125I-fibrinogen at 37 degrees C. Clotting was initiated with human thrombin, and lysis was monitored both turbidimetrically and by release of 125I-fibrin degradation products (fdp). The activity of t-PA (50 IU/ml) was rapidly reduced to 15% of the initial value in plasma containing PAI-1 (23 AU/ml). When thrombin and t-PA were added simultaneously to the plasma, more than 70% of the activity was retained through incorporation of t-PA into the fibrin clot. t-PA-induced fibrinolysis in PAI-1 enriched plasma was further delayed when the temperature was reduced from 37 to 25 degrees C. Turbidimetric and 125I-fdp release data provided complementary information. The former technique traced fiber dissolution, while the latter reflected network integrity. These results indicate that t-PA-induced fibrinolysis in PAI-1 enriched plasma is modulated by the presence of fibrin and by temperature. PMID- 1615465 TI - No evidence for short-term regulation of plasminogen activator inhibitor activity by insulin in man. AB - In cross-sectional studies a positive correlation has been found between circulating insulin, triglycerides and plasminogen activator inhibitor (PAI-1) activity. To directly examine the effect of insulin on PAI-1 activity in vivo, we determined the response of PAI-1 activity in 17 normal subjects to acute hyperinsulinemia (serum free insulin 92 +/- 8 mU/l) during maintenance of normoglycemia (plasma glucose 5.1 +/- 0.1 mmol/l). In 12 matched control subjects PAI-1 activity was measured during infusion of saline (serum free insulin 3.6 +/- 0.3 mU/l, plasma glucose 5.2 +/- 0.1 mmol/l). Plasma PAI-1 activity decreased during the insulin infusion from 9.0 +/- 1.4 to 5.6 +/- 0.8 U/ml (p less than 0.01), and during saline infusion from 7.0 +/- 1.4 to 4.3 +/- 0.6 U/ml (p less than 0.05). Serum triglyceride concentrations decreased from 1.09 +/- 0.20 to 0.76 +/- 0.09 mmol/l (p less than 0.001) during hyperinsulinemia but remained unchanged during the saline infusion (1.04 +/- 0.11 vs. 1.02 +/- 0.12 mmol/l, NS). We conclude that insulin does not acutely change plasma PAI-1 activity, and that acute insulin-induced changes in serum triglycerides occur independently from those of PAI-1 activity. PMID- 1615466 TI - Transport of anti-glycoprotein IIb/IIIa-antibodies into the alpha-granules of unstimulated human blood platelets. AB - The redistribution of the antibody-glycoprotein (GP) IIb/IIIa complex was investigated with the immuno-gold labeling technique in order to trace its transport in resting platelets. Washed platelets were incubated in the presence of aspirin and a prostacyclin analogue (iloprost) with three different monoclonal antibodies (Gi3, J15 and P2) against GPIIb/IIIa. The examination of ultrathin serial sections showed that the surface labeling was internalized into the surface connected membrane system (SCS). Labels were found within the alpha granules after 40 min and the number of labels increased during longer incubation periods (max. 120 min). The transport possibly involved coated membranes. The alpha-granules were neither found to be altered during this process nor were any morphological signs of platelet activation detectable. The anti-GPIIb/IIIa complex remained membrane-associated during the transfer. These observations indicate that the membrane-GPIIb/IIIa complex was stable and transported from the surface into the alpha-granules of resting platelets. Since this transport was not influenced by iloprost or by aspirin it may be interpreted as constitutive endocytosis. PMID- 1615467 TI - Reaction of acetaldehyde with human platelets. AB - Platelet function defects observed in chronic alcoholics are not wholly explained by the inhibitory action of ethanol on platelet aggregation; they are not completely reproduced either in vivo by short-term ethanol perfusion into volunteers or in vitro by the addition of ethanol to platelet-rich plasma. As acetaldehyde (AcH) binds to many proteins and impairs cellular activities, we investigated the effect of this early degradation product of ethanol on platelets. AcH formed adducts with human platelets at neutral pH at 37 degrees C which were stable to extensive washing, trichloracetic acid hydrolysis and heating at 100 degrees C, and were not reduced by sodium borohydride. The amount of platelet adducts formed was a function of the incubation time and of the concentration of AcH in the reaction medium. At low AcH concentrations (less than 0.2 mM), platelet bound AcH was directly proportional to the concentration of AcH in the reaction medium. At higher concentrations (greater than or equal to 0.2 mM), AcH uptake by platelets tended to reach a plateau. The amount of adducts was also proportional to the number of exposures of platelets to pulses of 20 microM AcH. AcH adducts formation severely impaired platelet aggregation and shape change induced by ADP, collagen and thrombin. A positive correlation was established between platelet-bound AcH and inhibition of aggregation. SDS-PAGE analysis of AcH adducts at neutral pH demonstrated the binding of [14C]acetaldehyde to many platelet proteins. AcH adduct formation with membrane glycoproteins, cytoskeleton and enzymes might interfere with several steps of platelet activation and impair platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615468 TI - Effective reversal of warfarin-induced excessive anticoagulation with low dose vitamin K1. AB - Reversal of the anticoagulant effect of warfarin in patients with no active haemorrhage can be achieved by administration of intravenous vitamin K1. Currently recommended doses of intravenous vitamin K1, for this purpose often result in subsequent difficulties in anticoagulation. We observed the response to low dose intravenous vitamin K1 in patients requiring reversal of anticoagulant therapy. Ten consecutive patients received 1 mg and 21 further patients received 0.5 mg of intravenous vitamin K1. In 50% of the patients who received 1 mg of vitamin K1 the INR (International Normalised Ratio) fell below 2 at 24 h whereas in patients who received 0.5 mg the INR fell below 5.5 in all subjects after 24 h and in none did it fall below 2.0. No patient had any thrombotic or haemorrhagic complications and no difficulty was encountered in re-establishing anticoagulant control after 24 h. We recommend 0.5 mg of vitamin K1 as an effective and convenient method of predictable and fine control of oral anticoagulant therapy. PMID- 1615469 TI - Rapid isolation of human endothelial cells from whole blood using S-Endo1 monoclonal antibody coupled to immuno-magnetic beads: demonstration of endothelial injury after angioplasty. AB - The presence in whole blood of circulating endothelial cells (EC) has been a subject of debate for many years. It could represent a good marker of vessel injury. We demonstrate here that human endothelial cells can be directly isolated and identified in circulating blood by means of an endothelial cell specific monoclonal antibody, S-Endo1, coupled to micromagnetic beads. The specificity and efficacy of the assay were established using normal blood samples with cultured EC added. Specific rosettes formed between EC and beads could subsequently be isolated with a magnet. The rosetted cells were recovered with a yield greater than 80%. Their endothelial origin was confirmed by the positive labelling of von Willebrand factor and thrombomodulin, as well as the presence of Weibel-Palade bodies. We applied this method to demonstrate significantly increased levels of EC in venous and arterial human blood samples in patients undergoing heart catheterization. This new whole blood immuno-separation method may be useful in determining endothelial cell injury in vascular disorders. PMID- 1615470 TI - Processing and characterization of recombinant von Willebrand factor expressed in different cell types using a vaccinia virus vector. AB - The cloning of the cDNA encoding von Willebrand factor (vWF) has revealed that it is synthesized as a large precursor (pre-pro-vWF) molecule and it is now clear that the prosequence or vWAgII is responsible for the intracellular multimerization of vWF. We have cloned the complete vWF cDNA and expressed it using a recombinant vaccinia virus as vector. We have characterized the structure and function of the recombinant vWF (rvWF) secreted from five different cell types: baby hamster kidney (BHK), Chinese hamster ovary (CHO), human fibroblasts (143B), mouse fibroblasts (L) and primary embryonic chicken cells. Forty-eight hours after infection, the quantity of vWF antigen found in the cell supernatant varied from 3 to 12 U/dl depending on the cell type. By SDS-agarose gel electrophoresis, the percentage of high molecular weight forms of vWF varied from 39 to 49% relative to normal plasma for BHK, CHO, 143B and chicken cells but was less than 10% for L cells. In all cell types, the two anodic subbands of each multimer were missing. The two cathodic subbands were easily detected only in BHK and L cells. By SDS-PAGE of reduced samples, pro-vWF was present in similar quantity to the fully processed vWF subunit in L cells, present in moderate amounts in BHK and CHO and in very low amounts in 143B and chicken cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615471 TI - Hereditary cerebral hemorrhage with amyloidosis-Dutch type: a study of fibrinolysis. AB - In view of reported associations between increased bleeding tendency and systemically decreased alpha 2-antiplasmin in patients with systemic amyloid deposition we studied alpha 2-antiplasmin, fibrinogen, C-reactive protein and blood levels of locally produced endothelial hemostasis factors in the acute and quiescent phase in 16 patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). None of the factors measured in the quiescent phase of the disease was abnormal. In the acute phase, shortly after a stroke, only factor VIII:Ag was evidently elevated. We concluded that systemic abnormalities in the part of the fibrinolysis system studied are not likely to be responsible for multifocal and recurrent cerebral hemorrhages in HCHWA-D. The role of an elevated factor VIII:Ag level in the acute phase is unclear. PMID- 1615472 TI - von Willebrand factor in plasma and urine of men with premature coronary artery disease. AB - Plasma and urine samples from 17 men who had suffered a myocardial infarction before the age of 45 years were quantitatively and qualitatively analyzed for von Willebrand factor antigen (vWF), and compared with samples obtained from controls. The levels of vWF in plasma and its characteristic multimeric composition in the patient samples were not different from those of the controls. However, when analyzed for lower molecular weight components, plasma samples from some patients contained more degraded material than those of the controls as indicated by the presence of an extra protein band of vWF related material having a molecular weight of about 200 kDa. The levels in urine of vWF and the molecular weight of the fragments excreted did not differ between patients and controls. A relative increase in excretion of lower molecular fragments was, however, observed in the patient group. In a second group of 97 consecutive post infarction patients under the age of 45 years the extra 200 kDa vWF band was found in 46% of the patients, whereas it was not detected in control plasmas. Taken together these findings suggest that degraded forms of vWF occur in normal plasma and that a more extensive degradation may occur in patients with coronary atherosclerosis, which could account for the relative increase in the excretion of lower molecular weight fragments observed in these patients. PMID- 1615473 TI - The venous antithrombotic effect of LF 1351 in the rat following oral administration. AB - The venous antithrombotic effects of a novel chemical entity, LF 1351, were investigated in rats following single oral administration, in comparison with i.v. administered heparin. LF 1351 demonstrated a dose-related antithrombotic effect in three models of venous thrombosis. The compound was approximately equipotent in two models involving complete stasis of the vena cava and administration of factor Xa or porcine serum, giving respective ED50 values of 48.7 mg/kg and 36.7 mg/kg. LF 1351 was less effective in a model involving partial stasis in the presence of an endothelial lesion. In this case, the antithrombotic effect did not exceed 60-65%, the ED50 being 150 mg/kg. Heparin (50-300 micrograms/kg; 7.5-45.0 U/kg) was effective in all three models. At the approximate ED80 value against factor Xa-induced thrombosis (75 mg/kg) the antithrombotic effect of LF 1351 persisted for 6 h. The antithrombotic effect of LF 1351 (300 mg/kg) occurred without significant changes in APTT or thrombin time. PMID- 1615474 TI - Cytoplasmic localization of aequorin loaded into human platelets by a new method. PMID- 1615475 TI - Subunit composition of plasma von Willebrand factor (vWF) in two uremic patients with acquired vWF abnormalities. PMID- 1615476 TI - Prevention of hepatitis C virus infection in children with haemophilia A and B and von Willebrand's disease. PMID- 1615477 TI - The effect of DDAVP and placebo on platelet function and prolonged bleeding time induced by oral acetyl salicylic acid intake in healthy volunteers. PMID- 1615478 TI - Treatment of hemophilia A with a highly purified factor VIII concentrate prepared by anti-FVIIIc immunoaffinity chromatography. AB - To reduce the risk of pathogenic virus transmission associated with the therapeutic administration of plasma-derived anti-hemophilic factor (FVIIIc), a process utilizing anti-FVIIIc immunoaffinity chromatography to isolate FVIIIc has been developed. In addition, the starting cryoprecipitate solution has been treated with an organic solvent/detergent mixture to inactivate lipid-enveloped viruses. A final ion exchange chromatography step is used to further remove contaminants, e.g., anti-FVIIIc antibody, potentially leached with FVIIIc during the immunoaffinity step. The purified FVIII is stabilized for lyophilization and storage by the addition of human albumin. The monoclonal anti-FVIIIc antibody used in the immunoaffinity step of the process is not detectable in the final preparation. Viral reduction studies performed at specific steps of the process demonstrate that 11 logs of human immunodeficiency virus (HIV) and greater than 4 5 logs of other lipid-enveloped viruses are inactivated within the first 30 s of exposure to the solvent/detergent mixture and 4-5 logs of various model viruses, e.g. Endomyocarditis virus (EMC), are physically removed during washing of the immunoaffinity column. The lyophilized product is reconstituted using sterile water in a matter of seconds. The pharmacokinetics of Hemofil M were compared to those obtained using a standard heat-treated concentrate (Hemofil CT) in five severe factor VIII deficient hemophiliacs in a randomized, cross-over study. No statistically significant differences were observed in mean half life (p greater than 0.6) or median recovery (p = 0.4) between the two preparations. No clinically significant adverse effects were observed in patients receiving either FVIII preparation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615479 TI - Prevention of deep vein thrombosis following total hip replacement by low molecular weight heparinoid. AB - We assessed the safety and efficacy of the novel low molecular weight heparinoid Lomoparan (Org 10172) for the prevention of deep-vein thrombosis in patients undergoing elective total hip replacement in a randomized, placebo-controlled, double-blind trial in 197 consecutive patients. The heparinoid (750 anti-factor Xa-units, s.c., b.i.d.) was administered to 97 patients and 99 patients received placebo. Study medication was started preoperatively and continued for 10 days. Efficacy was assessed by bilateral phlebography at day 10, postoperatively. The incidence of deep-vein thrombosis was 56.6% and 15.5% respectively in the placebo and heparinoid treated patients (incidence reduction: 74%; P less than 0.001). This reduction was observed both for proximal-vein thrombosis (25% to 8%; P less than 0.005) and isolated calf-vein thrombosis (31% to 7%; P less than 0.001). No major hemorrhage was observed. The number of red-cell units transfused and drain fluid loss were comparable for the two study groups. Six patients in the heparinoid group and none in the control group developed minor wound hematomas (P less than 0.05). During an 8-week post-discharge follow-up period three patients with a normal venogram at day 10 developed clinically apparent venous thromboembolism, which was confirmed by objective testing. All three patients belonged to the heparinoid-treated group. We conclude that 750 anti-factor Xa units Org 10172 s.c. twice daily starting preoperatively is safe and effectively reduces early deep-vein thrombosis following elective total hip replacement. Further studies on the incidence of post-discharge thromboembolism are required. PMID- 1615480 TI - Deep vein thrombosis in obstetric patients: diagnosis and risk factors. AB - This study was performed to assess the prevalence of deep vein thrombosis (DVT) in consecutive obstetric patients with clinical symptoms of DVT, using impedance plethysmography (IPG) as the diagnostic method and to establish the safety of withholding anticoagulant therapy in patients with a repeatedly normal IPG. In addition, in patients with DVT the prevalence of coagulation and fibrinolytic disorders, which may explain the occurrence of venous thrombosis was investigated. Of the 77 obstetric patients with symptoms of DVT, 32 (42%) had an abnormal IPG. The remaining 45 patients had a repeatedly normal IPG and showed no venous thromboembolism during a 6 months follow-up period. Twenty percent (six patients) of the patients with an abnormal IPG had a coagulation or fibrinolytic abnormality. These observations suggest that serial IPG can be used effectively in the management of obstetric patients with clinically suspected DVT and that hemostatic abnormalities are frequently found in those patients with DVT. PMID- 1615481 TI - Recombinant tissue factor as substitute for conventional thromboplastin in the prothrombin time test. AB - Relipidated recombinant tissue factor (r-TF) has been assessed in comparison with conventional rabbit brain thromboplastin (Manchester Reagent) for its suitability for measurement of prothrombin time (PT). The International Sensitivity Index (ISI) of r-TF calibrated against the International Reference Preparation BCT/253 (human plain) was found to be 0.96 and 1.12 with instrumental and manual techniques. Our study of plasmas from patients with congenital deficiencies of clotting factors covering a wide range of severity demonstrates that r-TF is able to detect even minor deficiencies of factors involved in the extrinsic and common coagulation pathways. Patients with liver diseases were correctly diagnosed with a prevalence of abnormal results comparable for both reagents. Between-assay reproducibility expressed as coefficient of variation was 2.3% and 3.9% at normal and abnormal PT levels. In conclusion, our evaluation shows that relipidated r-TF possesses the necessary requisites of sensitivity, diagnostic accuracy and reproducibility which make it a suitable candidate for PT determination both for monitoring oral anticoagulant therapy and diagnosing congenital and acquired clotting factor deficiencies. Moreover, being a highly defined reagent it may constitute a step forward in the standardization of PT testing. PMID- 1615482 TI - A novel functional assay of protein C in human plasma and its comparison with amidolytic and anticoagulant assays. AB - A simple and fast method for the quantitative determination of protein C activity in plasma is here described. The first step consists in the conversion of protein C in the test sample into activated protein C by means of an activator isolated from Southern Copperhead venom. Subsequently, the degradation of factor Va, in presence of protein C-deficient plasma, is measured by the prolongation of the prothrombin time which is proportional to the amount of protein C in the sample. The dose-response curve showed a linear relationship from 6 to 150% protein C activity and the inter- and intra-assay reproducibility was 3.5% and 5.6% respectively. In normal subjects, a mean of protein C level of 98 +/- 15% of normal pooled plasma was found. Comparison with the anticoagulant assay in samples of patients with oral anticoagulant, liver cirrhosis, disseminated intravascular coagulation and severe preeclampsia revealed an excellent correlation (r = 0.94, p less than 0.001). Also, a similar correlation (r = 0.93, p less than 0.001) existed between amidolytic assay and the method here proposed for all the samples studied without including the oral anticoagulant group. These results allowed us to infer that this method evaluates the ability of protein C to interact with protein S, phospholipids, calcium ions and factor Va. PMID- 1615483 TI - In vivo characterization of a new synthetic thrombin inhibitor. AB - We have examined the in vivo pharmacology of DuP 714 (Ac-[D]-Phe-Pro boroArginine), a representative of a new series of synthetic thrombin inhibitors which contain a boronic acid derivative of arginine. Intravenous bolus injections of DuP 714 in anesthetized rats and conscious rabbits produced transient elevations of clotting times. Clinically relevant prolongations of the APTT were also observed in rabbits after i.v. infusion of less than 0.1 mg kg-1 h-1. Efficacy against venous thrombosis was demonstrated in a rabbit model of stasis induced thrombosis. Clots formed in 100% of control animals and only 33% of animals treated with 0.5 mg/kg DuP 714, and were less severe in treated animals. In a rabbit arterial-venous shunt model mimicking arterial thrombosis, occlusion occurred within 30 min in 72% of control animals vs. 11% of animals treated with 0.1 mg kg-1 h-1 DuP 714. Results indicate that DuP 714 is a highly effective anticoagulant which should be useful for the prevention of both venous and arterial thrombotic diseases. PMID- 1615484 TI - Presence and possible origin of epsilon(gamma-glutamyl)lysine isodipeptide in human plasma. AB - epsilon(gamma-glutamyl)lysine isodipeptide has been detected in normal human plasma by a sensitive HPLC technique in a concentration of 1.9-3.6 mumol/l. Incubation of in vitro clotted plasma at 37 degrees C for 12 h resulted in an increased amount of isodipeptide, and there was no further significant change when streptokinase was also present. Increased in vivo isodipeptide concentrations were also observed in hypercoagulable states and during fibrinolytic therapy. PMID- 1615485 TI - Characterization of the original Christmas disease mutation (cysteine 206--- serine): from clinical recognition to molecular pathogenesis. AB - Christmas disease was first reported as a distinct clinical entity in two manuscripts published in 1952. The eponym associated with this disorder, is the surname of the first patient examined in detail and reported by Biggs and colleagues in a paper describing the clinical and laboratory features of seven affected individuals. This patient has severe factor IX coagulant deficiency (less than 0.01 units/ml) and no detectable circulating factor IX antigen (less than 0.01 units/ml). Coding sequence and splice junctions of the factor IX gene from this patient have been amplified in vitro through the polymerase chain reaction (PCR). One nucleotide substitution was identified at nucleotide 30,070 where a guanine was replaced by a cytosine. This mutation alters the amino acid encoded at position 206 in the factor IX protein from cysteine to serine. The non conservative nature of this substitution, the absence of this change in more than 200 previously sequenced factor IX genes and the fact that the remainder of the coding region of this gene was normal, all provide strong circumstantial evidence in favour of this change being the causative mutation in this patient. The molecular characterization of this novel mutation in the index case of Christmas disease, contributes to the rapidly expanding body of knowledge pertaining to Christmas disease pathogenesis. PMID- 1615486 TI - Haplotype analysis of identical factor IX mutants using PCR. AB - We have detected the mutations in the factor IX genes from all of the haemophilia B patients registered at Malmo haemophilia centre and are currently examining the entire UK haemophilia B population. From these studies we have found 13 base substitutions which have recurred in 1-6 other, presumably unrelated, patients. In order to determine the minimum number of independent repeats of each mutation we have used PCR to examine the five factor IX polymorphisms forming the most informative combinations and we have characterised the haplotype of each patient. Patients with different haplotypes are assumed to be unrelated and thus to carry independent mutations. All but one of the 13 mutations occur in at least 2 haplotypes thus pinpointing 12 mutational hotspots and mutations that can be clearly considered detrimental. Two of the 13 substitutions occur at non-CpG sites. PMID- 1615487 TI - On the intraindividual and gender variability of haemostatic components. AB - The intraindividual variability in terms of coagulation analyses was explored in 10-16 samples collected from each of 15 women during one menstrual cycle. For comparison, six men were sampled six times during a period of 30 days. The following variables were analysed: FVII, FVIII, FX, vWF:Ag, vWF:ristocetin cofactor, fibrinogen, antithrombin, plasminogen and anti-plasmin. The results demonstrated mean coefficients of variation ranging between 4.5 (plasminogen) and 20.7 (vWF:Ag). In certain individuals, the intraindividual variability amounted to nearly 40%, in particular in the assays of FVIII and vWF:Ag. No direct relation between these two factors and oestradiol, progesterone or testosterone levels could be observed in our individuals. The implications of these variations are discussed in terms of disease prediction and diagnosis of coagulation disorders. PMID- 1615488 TI - Daytime fluctuations of plasminogen activator inhibitor 1 (PAI-1) in populations with high PAI-1 levels. AB - The mechanism underlying diurnal variations in PAI-1 as well as the cellular origin of PAI-1 in subjects with high PAI-1 levels are unknown. We evaluated diurnal changes (8:00 am vs 4:00 pm) in PAI-1 (functional and immunological assays), t-PA Ag and t-PA/PAI-1 complex levels in controls and subjects with high PAI-1 levels. Three test groups were recruited among obese hyperinsulinemic subjects, emergency care unit patients with inflammatory syndrome or infection and pregnant women. The classical afternoon decrease of PAI-1 level was observed in controls and obese subjects but its amplitude was greater in the latter. The decrease in t-PA Ag and t-PA/PAI-1 complex levels was the same in controls and in obese. As, in previous studies, elevated PAI-1 levels have been correlated with insulin resistance and a decrease in insulin sensibility has been described in the early morning, it is proposed that this "dawn phenomenon" could be implicated in the circadian variations of PAI-1 in controls and could be amplified in obese subjects. Great variability in PAI-1, t-PA Ag or t-PA/PAI-1 complex levels was observed in patients with acute inflammatory syndrome or infection for whom classical biorhythms are suppressed. No diurnal changes in PAI-1 and other fibrinolytic parameters were observed in patients with inflammatory syndrome or in pregnant women suggesting that other sources and/or other regulatory mechanisms of PAI-1 production are involved. PMID- 1615489 TI - Contrast venography, the gold standard for the diagnosis of deep-vein thrombosis: improvement in observer agreement. AB - To determine whether the Rabinov-Paulin or the long-leg venography technique should be preferred in the diagnostic management of patients with clinically suspected deep-vein thrombosis, two independent experienced radiologists blindly assessed two different series of venograms of consecutive outpatients with clinically suspected deep-vein thrombosis. Venograms were obtained from two outpatient clinics of primary referral centres. In one centre the venograms were performed according to the technique of Rabinov and Paulin with the use of 100 ml of radiographic material and spot films of the calf, popliteal and more proximal veins. In the other centre, long-leg films were obtained after the administration of 150 ml of contrast material. The percentage venograms adjudicated as inadequate by at least one radiologist and inter-observer disagreement for both series were used as the main study outcome measures. Prior to the study, both radiologists agreed on the standardized criteria for a normal, abnormal and inadequate test result using a separate set of films. An inadequacy rate of 20% was found for the Rabinov-Paulin venography series (n = 123), whereas only 2% of the 126 long-leg films were inadequate for interpretation (p less than 0.001). The inter-observer diagreement for inadequacy, presence or absence of deep-vein thrombosis was 21% for the Rabinov and Paulin venograms and 4% for the long-leg films (kappa, 0.65 and 0.92; 95% confidence intervals: 0.53 to 0.77 and 0.84 to 0.99, respectively; p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615490 TI - Liver blood flow as a major determinant of the clearance of recombinant human tissue-type plasminogen activator. AB - The influence of changes in liver blood flow on the clearance of rt-PA was studied both in healthy subjects and in a perfused rat liver model. Liver blood flow in healthy subjects was documented indirectly by the clearance of indocyanine green (ICG). Exercise reduced liver blood flow on average by 57% with a 95% confidence interval (95% CI) ranging from 51% to 62% (n = 5) and increased plasma levels of rt-PA activity (after an i.v. infusion of 18 mg of rt-PA over 120 min) by 119% (95% CI, 58%-203%) and rt-PA antigen by 91% (95% CI, 30%-140%). In the perfused rat liver model it was shown that halving or doubling of the physiological flow rate of a perfusate, containing rt-PA caused a proportional change in the clearance of rt-PA, while the extraction of rt-PA by the liver remained similar. In conclusion, liver blood flow is a major determinant of the clearance of rt-PA. This may have important implications for dosage of rt-PA in patients with myocardial infarction. PMID- 1615491 TI - Markers of coagulation and fibrinolysis after fractures of the lower extremities. AB - The study was performed to detect activation of coagulation and fibrinolysis in terms of prothrombin fragment 1 and 2 (F1 + 2), thrombin-antithrombin III complex (TAT), fibrin degradation products (FbDP), fibrinogen degradation products (FgDP), and soluble fibrin monomers (FM) in plasma from 39 patients with fractures of the lower extremities. We found substantially elevated levels of the molecular markers at admission and on the day after admission (Day 1) compared with control levels. Admission levels of F1 + 2, TAT, FbDP and FgDP were significantly higher compared with levels on day 1, whereas levels of FM were not significantly different between the two days. Generally there were good correlations between all markers of coagulation and fibrinolysis at admission whereas correlations were weaker or absent on day 1. In conclusion we found substantial haemostatic activation as a immediate response to trauma. Increased levels of F1 + 2, TAT, FM, FbDP and FgDP appear to be a normal physiological reaction after fractures of the lower extremities. PMID- 1615492 TI - Effect of exercise intensity on 6-keto-PGF1 alpha, TXB2, and 6-keto-PGF1 alpha/TXB2 ratios. AB - Six men (X = 27.3 yr) ran at 60%, 70% and 80% of maximal oxygen consumption on separate days for 30 minutes to determine exercise intensity effects on 6-keto PGF1 alpha, TXB2, and 6-keto-PGF1 alpha/TXB2 ratios. At rest, 6-keto-PGF1 alpha was 384 +/- 68.3 pg/ml; TXB2 was 147 +/- 55.6 pg/ml; and the 6-keto-PGF1 alpha/TXB2 ratio was 4.63 +/- 1.3. After exercise at 60%, 70%, and 80% TXB2 increased to 523.2 +/- 117.5, 611.7 +/- 155.4*, and 643.8 +/- 121.7* pg/ml, respectively (*p less than .05). Post-exercise ratios tended to be inversely related to exercise intensity; however, no statistically significant differences were found between these values. These data suggest that exercise-induced increases in TXB2 may be related to intensity. PMID- 1615493 TI - Hereditary heparin cofactor II deficiency and coronary artery disease. AB - We here present a Japanese family with type I hereditary heparin cofactor II (HC II) deficiency. The propositus (a 61-year-old man) suffered from angina pectoris and coronary artery disease was confirmed by coronary angiography. He underwent percutaneous transluminal coronary angioplasty (PTCA) four times in one year. Combined use of heparin, aspirin, and nitrates could not prevent the return of his symptoms and restenosis of segment 6 of the left anterior descending artery. His HC II activity and antigen levels were 49% and 50%, respectively, and his daughter also showed similar low levels. Cerebral infarction had occurred in two family members. Argatroban, a selective potent thrombin inhibitor, was administered after the fourth PTCA for the purpose of preventing reocclusion and achieved a successful outcome. A relationship between HC II deficiency and thrombosis has not yet been established. Our case suggests that standard heparin therapy is not effective in preventing restenosis in such individuals, in whom the process is accelerated by thrombin generation at the site where PTCA produces rupture of the atherosclerotic plaque. Argatroban may be more effective under low HC II conditions because of its potent inhibition of thrombin activity at sites of vascular wall damage. PMID- 1615494 TI - Procoagulant activity in bronchoalveolar fluids: no relationship with tissue factor pathway inhibitor activity. AB - Abnormalities in local coagulation may explain alveolar fibrin deposition which often accompanies human lung injuries. The purpose of this study was to investigate the generation of procoagulant activity (PCA) and tissue factor pathway inhibitor (TFPI) in selected bronchoalveolar lavage fluids (BAL) from controls (n = 7) and from patients with interstitial lung diseases (n = 9), Pneumocystis carinii (PCP) pneumonia (n = 11) and bacterial pneumonia (n = 8). As compared with controls a significant increase of PCA was observed in the three groups with lung diseases. PCA in BAL from patients with untreated interstitial lung diseases (PC Units mean of 162 +/- 48) was significantly higher than PCA of treated patients (PC Units 36 +/- 10; p less than 0.05). Increases of PCA paralleled protein levels in BAL and the protein/albumin ratios were comparable in the four groups. TFPI was significantly increased in PCP (p less than 0.02) and bacterial pneumonia (p less than 0.03), but only marginally increased in interstitial lung diseases when compared with controls. No correlation was found between TFPI and PCA in any of the four groups. These data indicate that increased procoagulant activity observed in various lung diseases is not counterbalanced by TFPI. PMID- 1615495 TI - Guanosine 5'-0-(3-thiotriphosphate) induced calcium release in human platelets is mediated by inositol 1,4,5-triphosphate. AB - Guanosine 5'-triphosphate (GTP) and its nonhydrolyzable analogs, such as guanosine 5'-0-(3-thiotriphosphate) (GTP gamma S), induce several responses in platelets including secretion, production of inositol 1,4,5-triphosphate (IP3) and mobilization of Ca2+ from intracellular sites. Because IP3 is well established as a second messenger in mobilizing Ca2+ from intracellular stores it has been generally assumed that Ca2+ release by GTP/GTP gamma S in platelets is mediated by IP3. However, studies in neuronal, hepatic and smooth muscle cells have suggested that IP3 and GTP/GTP gamma S activate Ca2+ release by distinct mechanisms and that IP3-independent mechanisms mediate GTP/GTP gamma S-induced Ca2+ release. In several tissues heparin inhibits binding of IP3 and blocks IP3 stimulated Ca2+ release in a competitive and specific manner. In the present studies, IP3 and GTP gamma S induced Ca2+ release and their relationship was examined in human platelets using heparin as a probe. In saponin permeabilized platelets, IP3 (0.05-5 microM) induced a prompt, dose-dependent release of Ca2+ (EC50 0.5 microM). GTP gamma S (1-50 microM) released Ca2+ in a dose-dependent manner with EC50 of 2 microM but with a time lag of 30-90 seconds. Exposure of platelets to 1 microM IP3 following a submaximal response with GTP gamma S (1 microM) resulted in a further increase in Ca2+ release but no further increase was noted on adding 1 microM IP3 following a maximal response with GTP gamma S (10 microM); similar findings were noted on reversing the order of addition of GTP gamma S and IP3 suggesting that these effectors release Ca2+ from the same source. IP3 (0.5 microM) induced Ca2+ release was blocked by low molecular weight (4000-6000) heparin (IC50 30 micrograms/ml). More importantly, heparin abolished GTP gamma S (2.5 microM) induced Ca2+ release (IC50 10 micrograms/ml). These results indicate that, in contrast to the findings in some other cells, in human platelets GTP gamma S-induced Ca2+ release is mediated largely by a mechanism involving IP3. PMID- 1615496 TI - Ticlopidine and platelet function in healthy volunteers. AB - The influence of a 4-weeks therapy with 500 mg ticlopidine daily on platelet function parameters was examined in 10 male healthy volunteers aged 20-33 years in order to extend the knowledge on the antiplatelet activity of this substance. Ticlopidine significantly (p less than 0.01) affected ex-vivo platelet aggregation induced by ADP and increased platelet sensitivity to the antiaggregatory action of PGI2. Generation of TXB2 from endogenous substrate during spontaneous clotting of blood (serum-TXB2), conversion of exogenous radiolabelled arachidonic acid into TXB2 and MDA-formation in isolated platelets were unaffected by the treatment. The TXB2-level in plasma of volunteers, however, was decreased, after administration of the drug. The diminished alpha granule content liberation (beta-thromboglobulin: p less than 0.01; PDGF: p less than 0.01; PF4 not significant) indicates that ticlopidine induces a decrease in platelet activity. The beneficial effect on release reaction is not associated with a decrease in TXA2-formation. Our results demonstrate that ticlopidine inhibits platelet activity, especially the PDGF-release. These results confirm the value of this drug in the prevention of atherosclerosis and its thromboembolic complications. PMID- 1615497 TI - Measurement of the zeta potential of human platelets by the use of laser-light scattering. AB - An instrument was developed to detect the shift in scattering of laser light that occurs when particles in suspension move in a chamber with an electrical load. The instrument measures the zeta potential of particles. We applied the instrument to study human blood cells. Platelet-rich plasma was used because of the stability of the suspension, without the sedimentation or autoaggregation that is often seen with red or white blood cells. The reproducibility of the measurements was satisfactory when there were enough platelets in the suspension. Platelets from healthy controls (n = 136) had a potential of -14.20 +/- 1.64 mV at the detection angle of 17.1 degrees. Platelets from patients with essential thrombocytosis (n = 16) or polycythemia vera (n = 8) had higher potentials than the healthy controls. PMID- 1615498 TI - The bleeding time in normal subjects is mainly determined by platelet von Willebrand factor and is independent from blood group. AB - Bleeding time (BT) is the most important test "in vivo" evaluating the primary hemostasis. No relationship between plasma von Willebrand factor (vWF) and BT has been found in normal subjects, whereas no data are available on the relationship between platelet vWF and blood group or BT in normal subjects. To clarify the reciprocal relationship between blood group, vWF and BT, we studied 177 normal subjects. The influence of blood group on BT was analyzed in 116 subjects and the distribution of platelet and plasma vWF between different blood groups in 111 subjects. Furthermore, in a subgroup of 50 subjects, a multivariate regression model, including age, platelet count, plasma and platelet vWF:Ag and Ristocetin Cofactor (RiCof), hematocrit, sex and O or non-O blood group was used to assess the joint influence of these variables on BT. BT was similar in O and non-O group (P = 0.310) and, although plasma vWF was significantly lower in O group (P less than 0.0001), platelet vWF content was similarly distributed (P = 0.873 vWF:Ag and P = 0.322 RiCof). Furthermore, platelet vWF was not correlated with plasma vWF (r = 0.06, P = 0.526). In the multivariate regression analysis, only platelet vWF, age and platelet count showed a significant, inverse correlation with BT (P = 0.004), explaining 25% of the total variation of this test. Platelet vWF resulted therefore the main determinant of BT. PMID- 1615499 TI - Platelet hypoaggregability in rats exposed to SART stress (repeated cold stress). AB - A prolongation of bleeding time accompanied by thrombocytopenia and abnormalities in coagulation-fibrinolysis systems has been observed in laboratory animals exposed to a chronic form of environmental stress induced by severe fluctuations of air temperature, known as SART (specific alternation of rhythm in temperature) stress. In order to clarify the hemostatic profile under SART stress in more detail, the present study examined platelet aggregability in vitro as well as in vivo in stressed rats. During exposure to stress, thrombocytopenia developed from day 5, and remained up to at least day 14. In vitro aggregation of platelets stimulated by ADP or collagen was markedly decreased in stressed rats, compared with unstressed rats. Furthermore, stressed rats exhibited in vivo hypoaggregability of platelets, as estimated by the magnitude of the drop in circulating platelet counts following intravenous injection of ADP and collagen. Protein and cholesterol content in platelets remained constant after stress exposure. These results indicate that SART-stressed rats exhibit platelet dysfunctions in addition to thrombocytopenia. Considering the previous findings, the hemostatic system under SART stress appears to show a general tendency toward hemorrhage. PMID- 1615500 TI - Significance and quantitative analysis of von Willebrand factor in human platelets. AB - The von Willebrand factor (vWF) is found in plasma and in platelets. The concentration and multimeric composition of the vWF in platelets of 160 patients with bleeding tendency were examined since very little is known about the platelet vWF. For quantitative analysis of the platelet vWF, a modified ELISA was established. A reference range from 70%-130% of platelet vWF concentration considered normal was established by examining 80 healthy blood donors. 16.9% of the 160 patients showed a decreased vWF concentration in platelets only, while all the other coagulation parameters were normal. 3 of our patients belong to the same family and suggesting an autosomal dominant genetic transmission for the von Willebrand disease type 1-3. The data also suggests, that a quantitative and qualitative analysis of the vWF in plasma and platelets is required for an exact diagnosis of the von Willebrand disease. PMID- 1615502 TI - Statistically evaluated chromogenic rate assay of zymogen activation via spectrophotometer-computer interface. PMID- 1615501 TI - Serotonin is involved in some effects of erythropoietin. PMID- 1615503 TI - [Drug therapy of rheumatoid arthritis--a status quo?]. PMID- 1615504 TI - [Programmed cell death--significance for cancer etiology and treatment]. PMID- 1615505 TI - [Functional dyspepsia]. PMID- 1615506 TI - [Pathogenetic aspects of sarcoidosis. Importance of local complement synthesis in alveolar macrophages]. AB - Sarcoidosis is a multisystem granulomatous disorder of unknown etiology. Markers of activity include elevated serum ACE levels, interleukin 2-receptors, hypercalcemia, hypercalciuria, intrathoracic uptake of radioactive gallium, retinal vascular leakage, and an increased T4/T8 ratio in bronchoalveolar lavage fluid. The three main pathological features of sarcoidosis are alveolitis, granuloma formation and fibrosis. The cells harvested by bronchoalveolar lavage in sarcoidosis are representative of the local inflammatory reaction seen in the lung. Alveolar macrophages have the potential to synthesize the components of the functional alternative and terminal pathways of complement. The alveolar macrophages from sarcoidosis patients produce more complement than their healthy counterparts. Complement participates in the normal metabolism of immune complexes and has the ability to modulate immune responses via complement receptors present on virtually all cell types. On the other hand, through enhanced levels of complement factors, an increased number of activated macrophages in the lung may contribute to a changed immune response, which may be of significance for the granulomatous inflammation seen in sarcoidosis and may also contribute to the tissue damage seen in sarcoid fibrosis. PMID- 1615508 TI - [Bronchial carcinoid]. AB - A total of seven patients with bronchial carcinoids were treated at our hospital during the period from 1975 to 1991. Debut of symptoms varied from eight months to ten years before diagnosis. Cough, copious mucus, hemoptysis and recurrent lobar pneumonias were common. Six tumours were identified by chest X-ray. All tumours were visualised bronchoscopically; five showed as cherry-red polypoid tumours, one as a necrotising tumour and one as a stenosis of the bronchus. One patient underwent pneumonectomy, three lobectomy, one bilobectomy, one segment resection and one sleeve resection and lobectomy combined. Two cases were complicated by empyema and one was not radically operated due to impaired cardiopulmonary function. None showed carcinoid syndrome. All patients are still alive, and no recurrences or metastases have appeared. PMID- 1615507 TI - [Myasthenia gravis]. AB - Myasthenia gravis, first described in 1672 by Sir Thomas Willis and named by Jolly in 1895, is clinically characterized by muscular weakness relieved by rest. The incidence rate is about 4/million/year, the prevalence in Norway is about 100/million. Anticholinesterase drugs, introduced by Mary Walker in 1934, are still the primary therapeutics. Since about 1960 the disease has been recognized as autoimmune. Circulating antibodies to the acetylcholine receptor of the neuromuscular synapse are detectable in greater than or equal to 85% of the patients. Hence thymectomy, plasmapheresis and immunosuppressant drugs are useful. The thymus is recognizably pathological in 75-80% of the cases. The thymic hormone thymopoietin stimulates thymocytes and T-cells, and directly blocks the acetylcholine receptor. PMID- 1615509 TI - [Primary suture of the posterior cruciate ligament]. AB - 23 acute midsubstance ruptures of the posterior cruciate ligament were treated by primary suture. 20 patients returned for follow-up. Four of them had an isolated rupture of the PCL. The remaining 16 patients had sustained combined injuries to ligaments, including eight total ruptures of the anterior cruciate ligament. All ruptured ligaments were sutured. At follow-up (median = 5.5, range 3-10 years) median knee score according to Lysholm was 81 (range 53-100). Five were rated excellent, six good, three fair and six poor. KT-1000 arthrometer measurements revealed a posterior instability of between 5 and 10 mm in five patients and below 5 mm in 14 patients. Thus, in most patients, some instability remained in spite of operative treatment. PMID- 1615510 TI - [Urinary excretion of cannabis metabolites]. AB - Urine testing is increasingly used to detect drug abuse, most commonly by easily performed immunological tests. There is large interpersonal variation in the excretion time of cannabinoids. Excretion times of up to 11 weeks have been demonstrated. In cases with a long excretion time a negative test result may be followed by a positive result without concomitant abuse. We describe a case where cannabinoid metabolites in urine were detected by a routine immunological method (Abbotts ADx) after 95 days of supervised abstinence. It is important that personnel evaluating test results have a thorough knowledge of possible pitfalls. PMID- 1615511 TI - [Burns]. AB - Extensive burns are severe, life-threatening injuries. Cutaneous burns are often accompanied by injury to inhalation, leading to severe pulmonary problems with a high rate of mortality. Published reports on series of burn patients state that in 2-5% of all (burn) cases, cutaneous thermal injury was accompanied by mechanical injuries such as fractures, closed head injuries, or blunt injuries to chest and abdomen. The care of the burn is often made difficult by concomitant orthopaedic injury, and in a multiple trauma victim, the burn itself often complicates diagnosis and treatment. It is important to recognize all injuries as soon as possible. The article briefly discusses practical considerations when treating patients with multiple injuries including cutaneous burns and/or inhalation injury. After initial resuscitation and stabilization these patients should be transferred to a specialized treatment facility for burns. As a rule, open surgical reduction and fixation of fractures should be carried out no later than 48 hours after the injury. PMID- 1615512 TI - [Gunshot wounds and explosion injuries]. AB - The severity of injury inflicted by a missile is determined by the structure hit and retardation of the missile and thus the energy dissipated to the tissue. The injury to tissue depends on the kinetic energy and the construction of the missile, and the density and resilience of the tissue. Devastating, heavily contaminated wounds are inflicted by close-range shotguns and high-energy missiles, and thorough wound debridement and delayed primary closure are required after about four days. In general, it is not necessary to remove the missile unless this can be done easily. Explosions in air can cause burns, shrapnel wounds, acceleration and deceleration injuries. The shock wave dissipates energy on the border between air and fluid. This injuries primarily hollow organs such as lungs and intestines. Casualties from blasts may exhibit no external symptoms or signs of lung or intraabdominal injury. It is necessary to perform serial physical examinations, blood gas analyses, chest X-ray or CT scan. PMID- 1615513 TI - [Apoptosis and cytostatic agents]. AB - There are two distinct modes of cell death: necrosis and apoptosis. Apoptosis is an active process that may require gene expression and protein synthesis, and for this reason apoptosis has been called programmed cell death. Cancer cells in culture exposed to several anticancer drugs show morphological and biochemical characteristics consistent with apoptosis. This observation has possible impact on chemotherapeutic treatment of cancer. In this article we survey apoptosis, with emphasis on the relationship between apoptosis and anticancer drugs. PMID- 1615514 TI - [Preventive low dosage treatment and pre-eclampsia]. AB - Pregnancy-induced hypertension and pre-eclampsia occur in 10% of pregnancies and are recognised as important and prevalent sources of risk to both mother and foetus. Although the exact cause of the disease is unknown, several mechanisms have been suggested, including enhanced sensitivity to vasopressors and imbalance in the production of prostaglandins. This may lead to vasoconstriction of small arteries, activation of platelets and uteroplacental insufficiency. Since thromboxane A2 and prostacyclin are derived from arachidonic acid through the action of cyclooxygenase, low dose aspirin selectively inhibits the synthesis of platelet thromboxane A2 without affecting production of endothelium-derived prostacyclin. Data available from clinical trials suggest that, when given to high risk patients, low dose aspirin reduces risk of preeclampsia and intrauterine growth retardation by 50%, with no observed risk of adverse effects to either mother or foetus. PMID- 1615515 TI - [Endocavitary radiotherapy of rectal cancer]. AB - Most patients with rectal carcinomas undergo surgery, either a resection with anastomosis or Miles' operation with permanent colostomy. Endocavitary radiotherapy is an alternative to surgery in patients with small carcinomas (Dukes' A) or adenovillous adenomas. The treatment is cheap, simple, gives good local tumour control, has low morbidity and does not require hospitalization. The Norwegian Radium Hospital has recently started to use this method in selected cases of rectal carcinomas. PMID- 1615516 TI - [Gastric and duodenal probe]. PMID- 1615517 TI - [Functional dyspepsia--a stress disease]. AB - Because non-ulcer dyspepsia is associated with stress and motility disturbances it is now called functional dyspepsia. Compared with healthy persons, patients with functional dyspepsia are characterized by poor vagal tone, wider gastric antrum both fasting and postprandially, lack of stress-related repression of antral motility and meal-induced dyspeptic symptoms. Postprandial discomfort is related to antral distension. Poor vagal tone may cause antral distension and dysmotility as well as symptoms in these patients. Treatment programmes or drugs which improve vagal tone may be beneficial. PMID- 1615518 TI - [Use and disposal of drugs at home. Experiences of a community campaign for drug collection]. AB - We carried out a campaign to encourage return of medicines stored in private homes. 248 out of 1,512 households in our district returned average ten containers of drugs. 90% of these had been opened before return. Three out of four containers were outdated. A questionnaire was sent to all 1,512 households. 33% responded. All but six households kept medicines at home. An average of nine products were stored in each home. Half of the products were non-prescription drugs. Half of the households had medicine cabinets. The kitchen was the room most often used to store medicines. We discuss various efforts to achieve more simple return of unwanted drugs. We must emphasize the need to store medicines at home in a safe place. PMID- 1615520 TI - [The superpill which prevents myocardial infarction]. PMID- 1615519 TI - [Risk factors and mortality of myocardial infarction in Kristiansund, Alesund and Molde]. AB - We have examined mortality from ischaemic heart disease, prevalence of self reported coronary heart disease and risk factor levels in three towns (Kristiansund, Alesund and Molde) in the county of More og Romsdal. The results for mortality were based on vital statistics for the age group 40-69 years, for the periods 1966-76 and 1977-87. Risk factor data and data on self-reported coronary heart disease for the age groups 40-42 years and 65-67 years were obtained from a health screening survey conducted in the county in 1990. According to the official statistics, the towns share important socio-economic characteristics, but Kristiansund is thought to have stronger roots in the coastal culture, with a historically economic basis in fishery and shipbuilding. We observed substantial differences between the three towns, both as regards risk factor levels and mortality from ischaemic heart disease. By far the highest mortality rates were found in Kristiansund, both for men and for women. A similar gradient existed for the levels of main risk factors, including serum cholesterol, systolic blood pressure and prevalence of smokers. We discuss the implications of these findings for prevention strategies. PMID- 1615521 TI - [HIV infection and professional secrecy]. PMID- 1615522 TI - [Doubts about atenolol in the treatment of hypertension]. PMID- 1615523 TI - [Should HIV-positive persons selling sex be protected?]. PMID- 1615524 TI - [People and biotechnology--hearing statement of the Medical Society]. PMID- 1615525 TI - [Emergency helicopters--a health service in the grey zone?]. PMID- 1615527 TI - [Limitations of social insurance--beginning of the end of the social democratic welfare state?]. PMID- 1615526 TI - [A valuable search program for Medline]. PMID- 1615528 TI - [New signals in the medico-ethical thinking?]. PMID- 1615529 TI - [Various experiences with the use of the quantitative buffy coat analyzer (QBC) in the horse]. AB - Usability, repeatability and accuracy of the quantitative buffy coat analyser, QBC2, have been tested for the horse. The analyser provided reasonable results. The correlation between the data obtained with the QBC2 and those obtained with conventional techniques was found to be good. PMID- 1615530 TI - [Probiotics]. AB - Probiotics, living cultures of micro-organisms, are currently of great interest as counterparts to antibiotics. The idea behind the use of probiotics is that the development and stability of intestinal microflora can be enhanced. The protection against infections is increased, resulting in fewer health problems and increased productivity. The mechanism of action of probiotics is not yet known, although there are several hypotheses. There is increasing evidence to suggest that probiotics act by stimulating the host's immune systems. The only accepted example of effective protection against infections provided by living micro-organism is the 'Nurmi concept', whereby one-day-old chicks acquire an enhanced protection against Salmonella infections when they are administered the complex intestinal flora of older chicks. The effects of probiotics on the growth, feed conversion or production of farm animals are, even in specific situations, not consistent enough to consider their use out of economic considerations. Probiotics are used to (re)establish the intestinal flora of patients or persons with lactose intolerance. The claims that probiotics have cholesterol-lowering and anti-tumour actions are based on animal experiments and require further investigations. PMID- 1615531 TI - Regional differences in rat brain lipids during global ischemia. AB - BACKGROUND AND PURPOSE: Membrane lipid degradation plays an important role in the pathogenesis of ischemic brain damage, but there is little information on changes in cerebrosides, sulfatides, and sphingomyelin. We studied regional changes in the quantities of these lipids during complete global brain ischemia in rats. METHODS: Nitrous oxide-anesthetized rats were subjected to ischemia by a high pressure neck cuff and arterial hypotension for 0 (control), 3, 10, or 30 minutes (n = 5 at each time). Brain temperature was allowed to fall spontaneously during ischemia, and the brain was frozen in situ with liquid N2 without recirculation. The frontal cortex, hippocampus, and basal ganglia were dissected at -15 degrees C. The lipids were separated by column and high-performance thin-layer chromatography and quantified by charring and densitometry. RESULTS: Total lipid content was higher (p less than 0.01) in the hippocampus (72.6 +/- 2.8 mg/g wet wt, mean +/- SD) than in the frontal cortex and basal ganglia (57.7 +/- 2.1 and 62.6 +/- 1.5 mg/g wet wt, respectively). Ischemic changes occurred only in the frontal cortex, where total lipid content fell (p less than 0.01) by 11% after 30 minutes of ischemia because sulfatide and cerebroside contents fell by 44% and 38%, respectively. CONCLUSIONS: Despite a marked accumulation of free fatty acids during complete global brain ischemia in rats, the only detectable changes in brain lipids were in the amounts of cerebrosides and sulfatides in the frontal cortex. PMID- 1615532 TI - Transesophageal echocardiographic detection of aortic arch disease in patients with cerebral infarction. AB - BACKGROUND AND PURPOSE: Ulcerated plaques in the aortic arch are frequent autopsy findings in patients with cerebral infarctions, particularly those of unknown cause. It has been suggested that they could be a source of cerebral emboli. Using transesophageal echocardiography, we prospectively studied 12 consecutive patients with cerebral infarction of undetermined cause after noninvasive workup to evaluate the frequency of aortic plaques or mural thrombi that could embolize in cerebral arteries. SUMMARY OF REVIEW: Six patients (50%) had an intraluminal echogenic mass of the aortic arch, mainly located at the junction of the ascending aorta and arch. This material was pedunculated (in one patient) or broad based (in five patients) with a markedly irregular surface and intraluminal extension from 3 to 15 mm. In addition, we found cholesterol emboli in two of the four patients who underwent quadriceps biopsy. CONCLUSIONS: These results show that transesophageal echocardiography has capabilities in detecting such lesions and point to the aortic arch as a possible source of cerebral emboli in patients with cerebral infarction of unknown cause. PMID- 1615533 TI - Early recurrent ischemic stroke. A case-control study. AB - BACKGROUND AND PURPOSE: Data concerning potentially treatable risk factors for early recurrent stroke are limited. Therefore, we carried out a retrospective case-control study to identify factors predisposing to early reinfarction. SUMMARY OF REVIEW: We identified all patients admitted to Duke University Hospital or the Durham Veterans Administration Medical Center during 1 year having two documented ischemic strokes within 90 days (n = 12 of 273). Twelve randomly selected patients matched for age, sex, and race but having only a single stroke served as controls. There were no significant differences between the groups with respect to a variety of factors including the presence of hypertension, diabetes, a history of transient ischemic attack, a history of stroke, cerebral site of the index stroke, and subtype of the index stroke. A potential cardioembolic source was more frequently identified in the patients with early recurrent stroke (seven of the 12 case-control pairs were discordant for a potential cardioembolic source; McNemar's chi 2 test, p less than or equal to 0.02). CONCLUSIONS: Of the variables examined, the presence of a potential cardioembolic source was the single statistically significant factor associated with reinfarction within the first 90 days after ischemic stroke. The limitations and possible therapeutic implications of these results are discussed. PMID- 1615534 TI - Increased plasma endothelin-1 in acute ischemic stroke. AB - BACKGROUND AND PURPOSE: Endothelins are a recently discovered group of most powerful vasoconstrictor peptides. Endothelin-1 is produced by endothelial cells, and endothelin-3 is derived from neuronal tissue. Theoretically, endothelin mediated vasoconstriction may enhance ischemic neuronal damage. This study aimed to measure plasma levels of both endothelins in patients with acute nonhemorrhagic cerebral infarction. SUMMARY OF REPORT: Plasma levels of endothelin-1 and endothelin-3 were measured by radioimmunoassay in 16 consecutive patients within the first 72 hours after the onset of nonhemorrhagic cerebral infarct, as diagnosed clinically and by computed tomography. There was a marked (fourfold) elevation in plasma endothelin-1 levels in the patients (median, 11.7 pg/ml; 25th and 75th centiles, 5.4 and 13.2 pg/ml) compared with those in a control group of 13 age-matched subjects (median, 2.56 pg/ml; 25th and 75th centiles, 2.4 and 3.0 pg/ml; p less than 0.0001). The first 24 hours after stroke onset were associated with higher endothelin-1 levels, and there was a trend to elevated levels with more severe neurological deficits. In all patients and controls endothelin-3 levels were below 0.5 pg/ml. CONCLUSIONS: Ischemic stroke is associated with acute and marked increases in plasma levels of endothelin-1. This may reflect enhanced production by damaged endothelial cells within the infarcted tissue. Local leakage of endothelin-1 may induce severe and prolonged constriction of collateral vessels and may therefore have a deleterious role in the pathogenesis and final outcome of cerebral infarction. PMID- 1615535 TI - Critical carotid and vertebral arterial occlusive disease and cough syncope. AB - BACKGROUND AND PURPOSE: Cough syncope typically occurs in patients with known chronic lung disease. The mechanism usually involves a combination of decreased venous return, increased cerebrospinal fluid pressure, and secondary hypocapnia, all resulting in cerebral arterial vasoconstriction. Cough syncope has not in the past been associated with occlusive cerebrovascular disease. CASE DESCRIPTION: We describe a 50-year-old man with a 6-month history of episodes of loss of consciousness during paroxysms of coughing. Physical examination showed asymmetrical upper extremity blood pressures and carotid and subclavian artery bruits. Pulmonary function studies were normal. Ultrasound and angiography showed total occlusion of the left common carotid artery, right internal carotid artery, and right vertebral artery; tight stenosis of the right subclavian artery; and a hypoplastic left vertebral artery. The patient had a left subclavian-to-left common carotid artery bypass and has had no syncope since that time. CONCLUSIONS: To our knowledge, this is the first reported case of cough syncope and severe cerebrovascular disease in which surgery led to amelioration of symptoms. Cerebrovascular occlusive disease may contribute to cough syncope. PMID- 1615536 TI - Spontaneous vertebral artery dissection initially mimicking myocardial infarction. AB - BACKGROUND AND PURPOSE: Vertebral and carotid artery dissections may present with very different signs and symptoms, making early recognition difficult. However, diagnosis should be established as soon as possible to prevent unnecessary diagnostic investigations and to institute adequate treatment. CASE DESCRIPTION: A 46-year-old man presented with severe intermittent pain of his left upper arm and general discomfort. During extensive cardiological evaluation for suspected myocardial infarction, a severe brain stem syndrome occurred. Ultrasound Doppler studies detected vertebral artery dissection, which was confirmed by angiography. CONCLUSIONS: The unusual initial presentation of vertebral artery dissection delayed an early diagnosis and adequate treatment. Because noninvasive methods are available today, their applications are recommended in similarly uncharacteristic circumstances. PMID- 1615537 TI - Familial intracranial aneurysms. A review. AB - BACKGROUND: A familial occurrence of intracranial aneurysms is defined by the presence of such aneurysms in two or more first to third-degree family members. Families with two affected members may represent accidental aggregation. Other families show a frequency compatible with an autosomal dominant mode of inheritance. A genetic basis is also suggested by the younger average age of familial cases with a ruptured intracranial aneurysm (42.3 years versus an age range of 50-54 years for nonfamilial cases), occurrence at the same site or a mirror site in sibling pairs, occurrence in identical twins, and the association of intracranial aneurysms with genetically transmitted disorders. SUMMARY OF REVIEW: No reliable data are available about the occurrence of familial intracranial aneurysms among all patients with ruptured aneurysms; a frequency of 6.7% has been reported from a retrospective study, but a large part of the "familial" occurrence can be explained by fortuitous aggregation. The pathogenesis of familial intracranial aneurysms is not fully explained; a (partial) deficiency of type III collagen has been reported in sporadic, but not in familial, cases. Clinical decision analysis shows how the risk of harboring an intracranial aneurysm and the age of the patient are the main determinants for elective screening; lifetime risk of rupture (and therefore age) and surgical risks are the determinants for neurosurgical treatment. CONCLUSIONS: Surgical treatment is recommended for patients aged less than 70 years with a moderate or low surgical risk, and screening (preferably by intra-arterial digital subtraction angiography) is recommended only for relatives aged 35-65 years. Magnetic resonance angiography may develop into a useful alternative for screening, but the risks of diagnostic procedures play only a minor role in the decision analysis. PMID- 1615538 TI - Confusion over the terminology of subcortical infarcts visible on computed tomography is widespread. PMID- 1615539 TI - Do not resuscitate orders for cerebrovascular accident patients. PMID- 1615540 TI - Surgical treatment of cerebellar infarction. PMID- 1615541 TI - Coronary artery disease and cardiac events with asymptomatic and symptomatic cerebrovascular disease. AB - BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the prevalence of coronary artery disease and coronary events during follow-up in patients with asymptomatic carotid stenosis, transient ischemic attacks, or small strokes. METHODS: We prospectively studied 60 consecutive patients with thallium-201 scintigraphy followed by coronary arteriography according to an established protocol. RESULTS: The 201Tl testing was abnormal in seven of 15 patients (47%) with asymptomatic carotid stenosis and in 19 of 44 patients (43%) with transient ischemic attacks or small strokes (p greater than 0.05). In 33 patients with no history of coronary artery disease, 11 (33%) had reversible 201Tl defects. In 26 patients with a history of coronary artery disease, 15 (58%) had reversible and/or fixed defects (p = 0.054 compared with patients with no history). A history of peripheral vascular disease was the only risk factor significantly associated with an abnormal 201Tl test (p = 0.032). Coronary artery stenosis of greater than 50% was identified in one or more vessels in 14 of 15 patients undergoing coronary arteriography. Over a mean follow-up period of 311 days, four patients (7%) developed new onset of angina. There were four coronary events among 14 patients (29%) with both a reversible area on the 201Tl and abnormal coronary arteriography. In comparison, there were only four coronary events among 46 patients (9%) without reversible defects on the 201Tl studies (p = 0.055). CONCLUSIONS: Our study demonstrates that one third of patients with no history of coronary artery disease had an abnormal 201Tl test and that nearly one half of patients with either symptomatic or asymptomatic cerebrovascular disease had abnormal 201Tl tests. Patients with a reversible 201Tl defect and significant stenosis by coronary arteriography were at higher risk for subsequent cardiac events. These findings demonstrate the utility of screening patients with asymptomatic and symptomatic cerebrovascular disease for cardiac disease. PMID- 1615542 TI - Progression of carotid atherosclerosis in Japanese patients with coronary artery disease. AB - BACKGROUND AND PURPOSE: Along with the recent changes in lifestyle in Japan, the incidence of coronary artery disease has increased while the incidence of stroke appears to be decreasing. We investigated the relation between the progression of carotid atherosclerosis and the severity of coronary artery disease in the Japanese population. METHODS: The 2-year change in extracranial carotid atherosclerosis in 50 Japanese patients who underwent coronary angiography was evaluated using carotid echotomography. To quantify the extent of carotid atherosclerosis, the maximal thickness measurements of all plaques were summed for an individual plaque score, except for new plaques found on reexamination. Carotid disease progression was evaluated by the sum of plaque score change and the thickness of the new plaque found on reexamination. RESULTS: The plaque score changed by -3.2 to 10.1 mm (mean +/- SD, 1.06 +/- 2.42 mm). The extent of coronary atherosclerosis (p less than 0.02) and serum total cholesterol level (p less than 0.01) were different between the progressing (n = 17) and the nonprogressing (n = 30) groups of carotid atherosclerosis when the progressing group included the patients with a delta plaque score of greater than or equal to 1.0 mm. Neither age, serum triglyceride level, serum high-density lipoprotein cholesterol level, pack-years of smoking, percentage of smokers, percentage of hypertensive patients, nor percentage of diabetic patients was different between the two groups. Carotid disease progression was significantly higher in patients with three-vessel coronary disease than in patients without significant coronary artery disease (p less than 0.005). There was a significant positive linear correlation between carotid disease progression and Gensini's coronary artery disease score (R = 0.411, p less than 0.005). CONCLUSIONS: Our data showed that severe coronary artery disease and a high serum total cholesterol level were strong predictors for carotid disease progression in Japanese patients with high rates of coronary artery disease. PMID- 1615543 TI - Ultrasonic measurement of the elastic modulus of the common carotid artery. The Atherosclerosis Risk in Communities (ARIC) Study. AB - BACKGROUND AND PURPOSE: The Atherosclerosis Risk in Communities Study is a prospective investigation of the etiology and natural history of atherosclerosis and the etiology of clinical disease in four US communities. METHODS: Noninvasive ultrasonic methods were used to determine mean wall thickness (WT), radius (R), and circumferential arterial strain (CAS) in the left common carotid artery of 3,321 white male and female study participants between the ages of 45 and 64 years. The mean and standard deviation of Young's elastic modulus (Y) in 5-year age groups were determined for each sex by combining the ultrasonic data with concurrent noninvasive measurements of pulse pressure (PP) in the right brachial artery using the equation Y = (R/WT) x (PP/CAS). RESULTS: Significant (p = 0.0001) age group differences in Y were observed in both sexes, with the mean value increasing from 701 kPa in women and 771 kPa in men in the 45-49-year-old age group to 965 and 983 kPa, respectively, in the 60-64-year-old age group. Significant (p = 0.0001) age group differences were also observed for WT, the WT/R ratio, PP, CAS, and the PP/CAS ratio in both sexes. A sex difference in Y was detected (male greater than female, p = 0.0006) only in the 45-49-year-old age group. Significant (p less than 0.0001) sex differences were found, with men having a greater lumen diameter calculated as 2 x (R - WT), a greater WT, and a greater 2R in all age groups. The WT/R ratio did not differ in both sexes in all age groups. CONCLUSIONS: Knowledge of the arterial wall elastic modulus and the parameters required for its determination can provide important insight into structural changes occurring within the arterial wall with age and sex, and possibly with the onset of very early arterial disease. PMID- 1615544 TI - Treatment of cerebellar infarction by decompressive suboccipital craniectomy. AB - BACKGROUND AND PURPOSE: We present an anecdotal series of 11 patients without past history of stroke with progressive neurological deterioration while on medical therapy for large cerebellar infarctions. Clinical signs of brain stem compression developed in these patients. Computerized tomography of the head confirmed mass effect from brain edema. It was the clinical judgment of the neurologists and neurosurgeons that each of these 11 patients would expire without surgical intervention. METHODS: All 11 patients (seven men, four women; mean age, 54 years) were treated with suboccipital craniectomy for decompression and temporary ventriculostomy for cerebrospinal fluid pressure monitoring and drainage. RESULTS: Seven patients demonstrated neurological improvement on the first postoperative day. Two patients returned to their previous jobs 3 months after surgery. The Barthel Index indicated that six individuals were functioning with minimal assistance within a follow-up period of 16-60 months. The remaining three were functionally dependent. No mortality was noted in this series. CONCLUSIONS: These results suggest that decompressive suboccipital craniectomy may be an effective, lifesaving procedure for malignant cerebellar edema after a large infarction. PMID- 1615545 TI - Doppler CO2 test as an indicator of cerebral vasoreactivity and prognosis in severe intracranial hemorrhages. AB - BACKGROUND AND PURPOSE: Transcranial Doppler ultrasonography is a noninvasive, reproducible technique that allows the assessment of CO2-induced cerebral vasomotor reactivity. We investigated the effect of CO2 changes on cerebral blood flow velocity in patients with severe intracranial hemorrhage and evaluated the relation between CO2 reactivity, intracranial pressure, and outcome. METHODS: Transcranial Doppler parameters, intracranial pressure, arterial blood pressure, and PaCO2 were measured simultaneously in 40 patients. To determine CO2 reactivity, the initial PaCO2 of each patient was lowered by at least 6 mm Hg by controlled hyperventilation. Relative CO2 reactivity was defined as the percent change in mean flow velocity per mm Hg PaCO2 (averaged during 20 heart cycles before and after approximately 15 minutes of increased hyperventilation). RESULTS: A significantly reduced relative CO2 reactivity was observed in the patient group compared with a healthy, age-matched control group. Relative CO2 reactivity was maintained significantly better in patients with moderate intracranial pressure than in patients with markedly increased intracranial pressure. An indirect correlation was found between intracranial pressure and relative CO2 reactivity (r = -0.89; p less than 0.001). Clinical outcome was significantly related to the initial relative CO2 reactivity. Whereas the patients with good recovery had shown a largely preserved reactivity (mean +/- SD, 3.4 +/- 0.7%) that did not differ significantly from the control group, there was a continuous decrease up to the patients who died (0.8 +/- 0.3%). CONCLUSIONS: Transcranial Doppler CO2 testing in patients with severe cerebral disease and elevated intracranial pressure provides useful information regarding hemodynamic state, prognosis, and determination of beneficial effects of specific therapy. PMID- 1615546 TI - Treatment of acute cerebral hemorrhage with intravenous glycerol. A double-blind, placebo-controlled, randomized trial. AB - BACKGROUND AND PURPOSE: Hitherto, treatment of acute cerebral hemorrhage with intravenous glycerol has not been evaluated in rigorous clinical studies with sufficient patient numbers. METHODS: We undertook a double-blind, stratified and randomized, placebo-controlled clinical trial. Only patients with a first stroke admitted to the hospital within 24 hours after onset of symptoms were recruited, provided computed tomography confirmed hemorrhage and informed consent was obtained. After stratification into alert, semicoma, and coma subgroups using the Glasgow Coma Scale, 107 patients received active treatment (500 ml of 10% glycerol in saline by intravenous infusion over 4 hours on 6 consecutive days) and 109 were given corresponding saline treatment. Using a variety of objective scoring systems, patients were followed up for up to 6 months. RESULTS: At follow up, all measures of outcome in the treated and control groups were very similar. At 6 months, respective mortality rates were 37 of 107 and 33 of 109. Corresponding mean +/- SD improvements in Scandinavian Stroke Study Group scores were 8.35 +/- 16.9 versus 11.55 +/- 15.6 (long-term) and 0.64 +/- 7.3 versus 2.40 +/- 6.9 (prognostic), and improvements in the Barthel Index ratings were 10.72 +/ 24.7 versus 13.95 +/- 23.3, respectively. Glasgow Coma Scale score improvements in the survivors were 0.81 +/- 1.5 and 1.16 +/- 1.7 in the treated and control groups, respectively. Hemolysis (generally subclinical) was the only adverse effect of glycerol noted. CONCLUSIONS: In the absence of any clinically or statistically significant difference in outcome between the treated and control groups, this trial provides no justification for glycerol therapy following acute cerebral hemorrhage. PMID- 1615548 TI - Discharge outcome after stroke rehabilitation. AB - BACKGROUND AND PURPOSE: The purpose of this study was to examine the relations between host characteristics (age and side of body affected) and program variables (lengths of stay in acute care and rehabilitation, levels of functional ability at admission and discharge, and rates of community discharge). METHODS: A sample of 7,905 patients was drawn from medical rehabilitation facilities enrolled in the Uniform Data System for Medical Rehabilitation who were admitted and discharged for the first time between January 1988 and June 1989. Data were analyzed using either chi 2 tests or z normal tests of proportions, and analyses of variance (ANOVA) and/or t tests. Significance was set at p less than 0.05, and statistically significant F ratios were examined using Student-Newman-Keuls tests. RESULTS: The average age of patients was 70.7 years (24% less than 65 years, 53% 65-79 years, and 23% greater than 79 years). Lengths of stay in acute care and rehabilitation, admission and discharge functional independence ratings, and rates of community discharge were generally inversely related to patient age. Patients with bilateral paresis had lower rates of community discharge than those with unilateral paresis, although this distinction was not evident in the older group. CONCLUSIONS: Results showed that older age and bilateral paresis are negatively associated with levels of independence at admission and discharge and with rates of community discharge. PMID- 1615547 TI - Emergency reversal of anticoagulation after intracerebral hemorrhage. AB - BACKGROUND AND PURPOSE: Although intracerebral hemorrhage is one of the most serious complications during oral anticoagulant therapy, there are no guidelines on emergency treatment with respect to reversal of anticoagulation effect in these patients. METHODS: We retrospectively compared laboratory data and clinical features in 17 cases of anticoagulant-related intracerebral hemorrhage treated with prothrombin complex concentrate (n = 10) or fresh-frozen plasma (n = 7). RESULTS: In the group of patients treated with prothrombin complex concentrate, the mean prothrombin time decreased from 2.83 to 1.22 International Normalized Ratio within 4.8 hours, compared with a decrease from 2.97 to 1.74 within 7.3 hours in those given fresh-frozen plasma (i.e., four to five times more rapidly after treatment with prothrombin complex concentrate) (p less than 0.001). Symptoms and signs of intracerebral hemorrhage, measured on an eight-graded Reaction Level Scale, progressed on average 0.2 grades in patients given prothrombin complex concentrate compared with 1.9 grades in those given fresh frozen plasma (p less than 0.05). In patients with prothrombin values above 1.46, clinical progression within 12 hours occurred in five of six cases. CONCLUSIONS: Treatment with prothrombin complex concentrate reverses anticoagulation more rapidly than fresh-frozen plasma, which might be of importance for the prevention of further bleeding. PMID- 1615549 TI - Pure sensory stroke. Clinical-radiological correlates of 21 cases. AB - BACKGROUND: Although pure sensory stroke is a relatively common lacunar syndrome, the responsible lesions are often unidentified because of their small size. I reported 21 cases of pure sensory stroke in which the lesions could be identified by head computed tomography and/or magnetic resonance imaging and correlated the clinical findings with the radiological lesions. SUMMARY OF REPORT: Eleven patients had thalamic strokes. Lacunes confined to the posterolateral part of the thalamus were found in nine cases, and hemorrhages of relatively large size were found in two. Five patients showed a loss of all sensory modalities, but six with very small lacunes showed minor or restricted sensory changes. Seven patients with lacunes or hemorrhages in the lenticulocapsular region or corona radiata showed abnormalities of spinothalamic tract sensation. Two patients with a small lacune and a hemorrhage in the pontine tegmentum showed a selective sensory deficit of the medial lemniscal type. One patient with a small cortical infarct showed a cortical sensory loss that was preceded by cortical sensory transient ischemic attacks. CONCLUSIONS: Pure sensory stroke can occur with lesions in various areas of the somatosensory system. Hemisensory deficits of all modalities usually are associated with a relatively large lacune or hemorrhage in the lateral thalamus, whereas tract-specific or restricted sensory changes suggest very small strokes in the sensory pathway from the pons to the parietal cortex. PMID- 1615551 TI - Cerebral plasminogen activator activity in spontaneously hypertensive stroke prone rats. AB - BACKGROUND AND PURPOSE: In the spontaneously hypertensive stroke-prone rat, it is unclear whether plasminogen activator plays a role in the development of stroke. The present study was undertaken to investigate brain levels of plasminogen activator activity in spontaneously hypertensive stroke-prone rats and Wistar Kyoto rats. METHODS: Plasminogen activator was purified from the brains of rats of both strains. The purification involved used ammonium sulfate precipitation, gel filtration, a zinc chelate-Sepharose column, and a concanavalin A-Sepharose column. Fraction I (0.15 M KCl-soluble fraction) and fraction II (2 M KCl plus 6 M urea-soluble fraction) were purified from both strains. RESULTS: Total plasminogen activator activity in the original homogenates for fractions I and II derived from spontaneously hypertensive stroke-prone rats was increased to twice the level found in Wistar-Kyoto rats. The final product purified from fractions I and II in both strains of rats revealed single bands of plasminogen activator activity on enzymatic analysis with a molecular weight of 72,000. The purified product had stronger S-2288 amidolytic activity than S-2444 amidolytic activity, and it also displayed fibrin-binding ability. CONCLUSIONS: The study demonstrated that there is an increased content of plasminogen activator in the brains of spontaneously hypertensive stroke-prone rats that might be related to the development of stroke. PMID- 1615550 TI - Pressure-flow relations in canine collateral-dependent cerebrum. AB - BACKGROUND AND PURPOSE: The pressure-flow relation has been characterized in normal cerebrum, but it has not been studied in cerebrum dependent on collateral flow. The purpose of this investigation was to examine the relation between systemic pressure, regional cerebral blood flow, and middle cerebral artery branch pressure in collateral-dependent and normal brain. METHODS: In 10 anesthetized dogs, we cannulated a branch of the middle cerebral artery and identified collateral-dependent tissues using the shadow flow technique. We measured pressure in normal and cannulated branches of the middle cerebral artery and regional cerebral blood flow. The common carotid arteries were occluded, and hemorrhage reduced mean arterial pressure to 50 and 25 mm Hg. RESULTS: When aortic pressure was 25 mm Hg, blood flow to the collateral-dependent zone decreased from a baseline of 87 +/- 5 to 6 +/- 1 ml/100 g per minute (mean +/- SE), and pressure in the cannulated branch of the middle cerebral artery decreased from 49 +/- 4 to 2 +/- 0.4 mm Hg (p less than 0.05). Small-vessel resistance in the collateral-dependent region decreased from 0.56 +/- 0.09 to 0.38 +/- 0.04 mm Hg/ml/100 g per minute (p less than 0.05) after carotid occlusion but did not change significantly during hypotension. In normal brain, however, small-vessel resistance continued to decrease as systemic pressure was reduced. CONCLUSIONS: This study provides pressure-flow relations in normal and collateral-dependent cerebrum during carotid occlusion and progressive hypotension. In collateral-dependent tissue, concurrent occlusion of middle cerebral and carotid arteries produces autoregulatory dilatation of small vessels, resistance fails to decrease as mean arterial pressure is reduced to 25 mm Hg, and profound focal hypoperfusion is produced. PMID- 1615552 TI - [Association of dentists of Winterthur (VWZ). Foundation and development]. PMID- 1615553 TI - [Differential diagnosis of epulis-type changes in the mouth]. AB - Various tumorlike reactions of the oral mucous membranes under the term Epulis are summarized. These histologically different benign or malignant neoplasms of the gingiva are not very frequent. The differential diagnosis on a clinical basis like symptoms and macroscopic appearance is not easy. Sometimes under these harmless appearing lesions highly aggressive and malignant tumors may be hidden; as there are carcinomas, sarcomas, metastases, tumors of the salivary glands or malignant lymphomas. The therapy of choice is the complete removal including the underlaying periosteum. Occasionally the adjacent bone and tooth have also to be resected. Because of the harmless clinical appearance a histological examination is always required. Some clinical and pathohistological impressive examples are presented. PMID- 1615554 TI - [Frequency of chromosome aberrations in peripheral blood lymphocytes of children living in regions with various radio-ecologic situations]. AB - First results of cytogenetic monitoring of children, living in contaminated regions of the Ukraine show statistically significant increase in quantity of chromosome aberrations, that is positively correlated with environmental situation. The effect found shows that damage of genome stability must be accounted as an indicator of increased possibility of gene-based pathology in studied groups as compared to control. PMID- 1615555 TI - [Heterophilic granulocytes of rats during irradiation]. AB - The bone marrow eosinophils of rats subjected to irradiation are capable of secreting a peroxidase system obtained by neutrophils and endotheliocytes. As a result, there appear heterophil granulocytes in the peripheral blood. PMID- 1615556 TI - [Analysis of the genetic predisposition to cancer in families of patients with multiple primary malignant neoplasms]. AB - Clinical-genetic examination of 305 patients with multiple primary tumors aimed at determining the rate of genetic burden to their development and community of joint accumulation of tumors in families of these patients has revealed a significant genetic community of inheritance of breast cancer, carcinomas of colon, endometrium, ovaries and stomach in the families of patients with multiple primary tumors. Comparative analysis of genetic correlations has shown the greatest genetic burden in families of patients with multiple primary tumours as against the families of patients with solitary cancer. PMID- 1615557 TI - [Genetic markers of individual predisposition to lung cancer]. AB - The investigation concerning the dependence of cancer incidence on genetic HLA markers and character of dermatoglyphs was carried out. The use of the pattern recognition method for multifactorial estimation of the above markers as well as the elimination of the main non-genetic oncogenic risk factors allowed obtaining the proof of the existence of the genetic predisposition to lung cancer. It was estimated that the character of dermatoglyphic prints is the most adequate marker for the investigated predisposition, and the reliable prediction of the genetic risk of the lung cancer development can be given as based on the joint evaluation of both markers. PMID- 1615558 TI - [Genetic polymorphism of hemoglobin, protein systems, blood enzymes and their relationship to reproducibility]. AB - The genetic polymorphism of haemoglobin, transferrin, amylase, alkaline phosphatase, ceruloplasmin, beta-lactoglobulins and casein were studied. The relationship between the level of the heterozygosity of the blood polymorphic protein and enzyme systems was determined. PMID- 1615559 TI - [Mutagenic activity of the plant preparation KAC-81]. AB - Mutagenic activity of vegetative preparation KAC-81 containing extracts of common wormwood and pine buds using crepis root seedlings, unicellular green alga of Chlorella indicator strains of Salmonellas TA 100, TA 1534, TA 1537, TA 50 and TA 98 as well as white mice and white rats has been studied. It is shown that the preparation caused a weak mutagenic effect on Crepis seedlings and Chlorella and no mutagenic effects on the indicator strains of salmonellas, in sex and somatic cells of mammals under single peroral action in maximally endured doses. PMID- 1615560 TI - [Retrospective study of the development of basic trends in human cytogenetics for 1981-1988]. PMID- 1615561 TI - [Spectacular advances in cardiology: molecular biology promises more to come. Interview by Robert Henry]. PMID- 1615562 TI - [Pneumococcal vaccine and the independently living elderly]. PMID- 1615563 TI - [Anxiety disorders in children: incidence, comorbidity and risk factors]. AB - According to epidemiological studies, prevalence of children's anxiety disorders is about 10%. Among children who suffer from anxiety disorders, a majority also presents one or more anxiety or mood disorders. The children's sex and age are likely to influence anxiety disorders. As well as the children's personality: studies about 'temperament' indeed pointed up this notion. Low socio-economic level of family could be a risk-factor, the importance of which varies according to anxiety disorders subtypes. Current and/or history of parental anxiety disorders, presenting or not with mood disorders, increase the risk for their children to suffer from anxiety disorders. PMID- 1615564 TI - [A diabetic patient presenting unduly precocious retinopathy and nephropathy]. PMID- 1615566 TI - [Angina: beware of apparent benignity]. PMID- 1615567 TI - [Angina: a unique research protocol in Quebec]. PMID- 1615565 TI - [Anatomo-clinical conference at the Hotel-Dieu de Montreal. A 34-year-old man with fever and hemoptysis]. PMID- 1615568 TI - Renal cystic disease in multisystem conditions. AB - Five renal cystic diseases have significant extrarenal manifestations: autosomal dominant polycystic kidney disease (ADPCK), autosomal recessive polycystic kidney disease (ARDCK), tuberous sclerosis (TS), von Hippel-Lindau Syndrome (VHL), and medullary cystic disease (MCD). Knowledge of these extrarenal manifestations is important since they may precede, present simultaneously, or follow the onset of the renal cystic disease. This article discusses the most significant extrarenal manifestations of these five renal cystic diseases: (1) ADPCK: hepatic cysts and cardiovascular abnormalities; (2) ARDCK: portal hypertension; (3) TS: hamartoma like tumors of other organs; (4) VHL: central nervous system hemangioblastomas and paragangliomas; and (5) MCD: congenital hepatic fibrosis. Detecting extrarenal manifestations may be helpful (1) in confirming the renal cystic disease; (2) in thoroughly evaluating the patient with known renal cystic disease, and (3) if they antedate the renal cystic disease, their presence will alert the radiologist to evaluate the kidneys. PMID- 1615569 TI - Imaging the urethra in men and women. AB - This review describes and illustrates the radiologic techniques, normal anatomy, and common congenital and acquired lesions of the urethra in men and women. Voiding cystourethrography and retrograde urethrography are the most common imaging modalities employed in the diagnosis of anatomic lesions of the urethra. The appearance of the urethra may then dictate the need for further functional evaluation with urodynamic studies. Congenital lesions in men include posterior and anterior urethral valves and duplicated urethra. In women, ectopic insertion of the ureter into the urethra is the usual congenital lesion. Acquired urethral lesions include benign prostatic hypertrophy in men and strictures and diverticula in both men and women. PMID- 1615570 TI - In utero sonography of genitourinary anomalies. AB - Congenital anomalies of the genitourinary system represent the commonest fetal anomaly. The sonographic findings in hydronephrosis, multicystic kidney (dysplastic kidney), polycystic kidney, and renal agenesis are reviewed. PMID- 1615571 TI - Multimodality approach to staging renal cell carcinoma. AB - Renal imaging has dramatically improved since the introduction of ultrasound (US), computed tomography (CT), and most recently magnetic resonance (MR) imaging. US and MR imaging are ideal for patients with compromised renal function preventing administration of iodinated contrast material or those who have experienced reactions to contrast. Staging errors occur due to limitations in assessing microscopic tumor invasion of the renal capsule and perinephric fat, detecting metastatic deposits in normal sized lymph nodes and differentiating inflammatory hyperplastic lymph nodes from neoplastic ones. These limitations are shared by US, CT, and MR imaging. Vascular invasion by tumor can be evaluated by all imaging modalities including venography. The advantages and limitations of each examination will be presented. PMID- 1615572 TI - The dilated urinary tract in children. AB - Dilatation of the urinary tract is detected in a number of settings throughout childhood. Children may be asymptomatic or present with urinary tract infection, hematuria, or voiding symptoms. Evaluation of the affected urinary tract may require standard radiographic techniques (VCUG, EU) complemented by ultrasound and nuclear medicine studies. The goal of imaging is to differentiate hydronephrosis (HN) from hydroureteronephrosis (HUN) and to provide the correct diagnosis so that appropriate treatment can be given. This article reviews and demonstrates the findings in some common and uncommon causes of HN and HUN. PMID- 1615573 TI - Renal transplantation: use of sonography. PMID- 1615574 TI - Diverticula of the male urethra: a review of 61 cases. AB - Sixty-one cases of diverticulum of the male urethra were reviewed. This group included 10 patients with congenital and 51 with acquired diverticula. The etiology of the acquired variety, the radiological findings, and the frequency of appearance in both congenital and acquired diverticula of the urethra during a 30 year period are described. PMID- 1615575 TI - Digital radiography in urologic imaging: radiation dose reduction on urethrocystography. AB - Digital luminescent radiography (DLR) is a new form of digital radiographic technology which can be used as an alternative to conventional radiologic systems; it replaces conventional screen-film systems by photostimulable phosphorus. Due to the linear dynamic range of photostimulable phosphorus, x-ray examinations can be performed with significantly lower radiation exposure. In this study radiation dose was reduced by about 90% using DLR for urethrocystography. PMID- 1615576 TI - Intracavernosal injection of prostaglandin E1 as an alternative for papaverine in penile angiography. AB - Arteriography of the penile vasculature was performed after intracavernous injection of prostaglandin E1 in five patients. Penile tumescence was obtained in three patients with a dose of 10 micrograms and in the other two patients with a dose of 20 micrograms. Mean duration of penile tumescence was 1 h 36 min. Visualization of the penile vasculature was adequate in all patients. Local pain was a minor side effect in one patient. These preliminary results suggest that prostaglandin E1 might represent an alternative for papaverine in the angiographic study of male impotence. PMID- 1615577 TI - Inguinal mass in a 66-year-old man. PMID- 1615578 TI - Contemporary concepts for imaging urinary tract obstruction. AB - Ultrasound is an integral tool in the contemporary assessment of urinary tract obstruction. Pulsed and color Doppler have eliminated many previous false positives due to blood vessels or non-obstructive hydronephrosis. Limitations of the ultrasound technique still exist and on occasion necessitate the utilization of intravenous urography. PMID- 1615579 TI - Interleukin-2-induced growth inhibition of prostatic adenocarcinoma (Dunning R3327) in rats. AB - The present study was designed to evaluate the effect of a biological response modifier, interleukin-2 (IL-2), on the growth in rats of Dunning (R3327, androgen sensitive) prostatic adenocarcinoma. IL-2 was given to one group of tumour bearing rats by subcutaneous infusion (Alzet micro-osmotic pump 2002, 14 days) of 424,286 IU/kg per day during 4 weeks. Another group was sham-operated and served as control. Tumour growth was calculated by weekly measurement of tumour volume. IL-2 treatment caused a significant growth delay without any significant toxicity. Plasma testosterone concentrations were similar in both groups and ventral prostatic weights did not differ. Morphometric analyses of epithelial cells, stroma, luminal compartment in tumour tissue and calculation of the number of intratumoral lymphocytes did not show any differences between the two groups. It is suggested that IL-2 treatment can decrease prostatic tumour growth without apparently affecting the testosterone metabolism. Further studies with special interest on the mechanism of action are justified. PMID- 1615581 TI - BCG treatment and the importance of an inflammatory response. AB - A prospective study was performed on patients with superficial bladder tumour treated with bacillus Calmette-Guerin (BCG). The kinetics of interleukin-6 (IL-6) titres were monitored in urine collected at regular intervals for 24 h during 14 BCG treatments, each consisting of six weekly intravesical instillations. IL-6 titres were quantified with an ELISA system and compared with a bioassay (biologically active IL-6) system. After instillation, urinary IL-6 titres transiently increased, reaching maximum levels between 2 and 6 h after instillation. IL-6 titres appeared to be significantly correlated with an increase of total cells retrieved by bladder washout 3 h after instillation. The kinetics of the weekly maximum biologically active IL-6 titres indicate that three types of BCG-induced response occur: an "early" response starting at the first instillation; a "late" response after the third instillation; or no IL-6 response. The "early" response appeared to be associated, but not strictly correlated, with an IL-2 response. The results suggest that the effectiveness of BCG treatment is determined by two processes, an inflammatory one, followed by a delayed type of hypersensitivity response. PMID- 1615580 TI - Differential sensitivity of hormone-responsive and unresponsive human prostate cancer cells (LNCaP) to tumor necrosis factor. AB - Two sublines, the hormone-sensitive LNCaP-FGC and the insensitive LNCaP-r (resistant) carcinoma cell lines, originating from the parental human prostatic carcinoma cell line LNCaP were tested for sensitivity to human tumor necrosis factor-alpha (TNF) using the MTT assay. Irrespective of the culture conditions, i.e., whether FGC cell growth was hormone stimulated or hormone deprived, a clear dose-related response was observed between the concentration of TNF (range: 5 5000 U/ml) in the culture medium and the percentage of growth inhibition. In medium containing androgen-depleted serum, in which FGC cells showed reduced proliferative activity, the percentage of inhibition by a concentration of 100 U/ml TNF was substantially higher than that found in hormone-stimulated cells (90% and 60%, respectively). In contrast to the FGC cells, the hormone insensitive LNCaP-r cells were almost completely resistant to the action of TNF. Growth of the FGC cells was almost completely inhibited, whereas growth of the LNCaP-r cells was retarded with only 20% at dosages up to 5000 U/ml. This substantial difference in TNF responsiveness could not be ascribed to differences in TNF-binding capacity, as both the FGC and LNCaP-r cells were found to contain identical numbers of TNF-receptors (approximately 1000 sites/cell). A possible association between hormone responsiveness and TNF sensitivity is suggested for these LNCaP sublines. PMID- 1615582 TI - Regulatory effects of interleukin-7 on renal tumor infiltrating lymphocytes. AB - Biological therapy using a combination of lymphokine and tumor infiltrating lymphocytes (TILs) is a new approach to the treatment of patients with advanced cancer. To improve the potency of TILs, new cytokines with T-cell stimulatory effects used alone or in combination with interleukin-2 (IL-2) are currently being investigated. We have studied the effect of interleukin-7 (IL-7) on TILs derived from renal cell carcinoma. Our data demonstrated that five of ten TILs proliferated in response to IL-7 alone. This proliferative response was 73-90% less than that obtained with IL-2 alone. The use of IL-7 plus IL-2 resulted in a 1.2- to 4.7-fold increase in proliferation of six of ten TILs compared with IL-2 alone. IL-7-driven TIL growth was consistently blocked by anti-IL-2, anti-IL-2R and anti-IL-7 antibodies (37.2%, 41.6% and 82.2% suppression, respectively). The expression of IL-2 receptors was also significantly increased in the presence of IL-7 or IL-7 phytohemagglutinin (40.6 + 3.8 and 72.5 + 1.5). In comparison with IL-2, IL-7 treatment was associated with a decrease in CD56 (46.3% +/- 19 vs 10% +/- 4.9) and increase in CD3 (29.3% +/- 12 vs 73% +/- 6.4) and CD4 (19.3% +/- 15 vs 58% +/- 10). These studies suggest that in some renal TILs, IL-7 and IL-2 can have a synergistic proliferative effect. The IL-7 stimulatory effect appears to be mediated via both an IL-2 pathway and an IL-7-independent pathway. PMID- 1615583 TI - Cytostatic effect of different strains of Bacillus Calmette-Guerin on human bladder cancer cells in vitro alone and in combination with mitomycin C and interferon-alpha. AB - The cytostatic activity of five Bacillus Calmette-Guerin (BCG) strains (Pasteur, Evans, Tice, RIVM and Connaught) on human transitional cell cancer T24 cells was examined. A striking effect was noted even in 2-day cultures, and the effect was more pronounced when the cells were incubated for 5 days with different BCG strains alone. The concentrations needed were about the same as those used in clinical practice (10(9) colony-forming units of Pasteur strain in 100 ml buffered saline solution). Combination with mitomycin C or interferon-alpha-2b potentiated the cytostatic effect. A slight difference in cytostatic activity between different BCG strains was found. PMID- 1615584 TI - Morphological aspects of the interaction of Bacillus Calmette-Guerin with urothelial bladder cells in vivo and in vitro: relevance for antitumor activity? AB - Intravesical administration of Bacillus Calmette-Guerin (BCG) has been shown to be effective in the treatment of patients with superficial bladder cancer. For a better understanding of the mechanism of this antitumor activity, scanning and transmission electron microscope (SEM, TEM) studies were carried out to investigate morphological aspects of the interaction of BCG with the bladder wall in vivo and in vitro. Adherence of BCG to the bladder wall in vivo was studied 1 and 24 h after single or multiple (6x) BCG instillations in intact and in electrocauterized guinea pig bladders. Despite extensive search with SEM for its presence, virtually no BCG was found on the intact urothelium, and BCG was only occasionally observed in the coagulation lesions. SEM and TEM studies revealed adherence and phagocytosis of BCG by the T24 human bladder carcinoma cell line in vitro. Time sequence studies on the phagocytosis and fate of BCG showed that T24 cells are capable of progressively degrading the mycobacteria in phagolysosomes. However, BCG did not alter MHC class II antigen expression on T24 cells in vitro. In contrast, 54 urine sediments and bladder washings of 11 bladder cancer patients, taken prior to or after several intravesical BCG instillations, failed to demonstrate urothelial (tumor) cells showing evidence of BCG phagocytosis (682 cells screened by TEM), while BCG was phagocytized avidly by leukocytes. These data suggest that a direct interaction of BCG with urothelial bladder cells in vivo can be called in question. PMID- 1615585 TI - Dimethylsulfoxide enhances the absorption of chemotherapeutic drug instilled into the bladder. AB - We examined the effect of dimethylsulfoxide (DMSO) on the absorption of a chemotherapeutic drug instilled into the bladder. Female Wistar rats with bladder tumors underwent intravesical instillation of normal saline (S group) or 50% DMSO (D group) prior to the administration of pirarubicin (tetrahydropyranyl Adriamycin). The absorption of pirarubicin was estimated histologically by observing its fluorescence. In the S group, fluorescence of pirarubicin was observed only in the epithelial layer of normal or hyperplastic regions and in the cells of superficial layers of the tumor. In the D group fluorescence was observed in the entire bladder wall of normal or hyperplastic regions and extended to deeper regions of the tumors than in the S group. These findings indicate enhancement of the absorption of pirarubicin by pretreatment with DMSO. PMID- 1615586 TI - Responses of tumour cell lines implanted onto the chorioallantoic membrane of chick embryo to anticancer agents in combination with hyperthermia. AB - The chorioallantoic membrane of chick embryos was used to examine the responses of three tumour cell lines to anticancer agents, alone and in combination with hyperthermia. Fifteen minutes of hyperthermia at 42.5 degrees C produced the most favourable anticancer effect in the B16-F10 grafts. The use of Adriamycin (ADM) alone and the combined use of hyperthermia and either cisplatin (CDDP), cyclophosphamide (CY) or ADM resulted in a significantly higher rate of tumour regression in the B16-F10 grafts from a murine melanoma. In the KK-47 grafts derived from a transitional cell carcinoma of the bladder, the use of CY alone and the combination of CY and hyperthermia produced a significant tumour regression rate. In the T24 grafts neither the use of CY or CDDP alone, nor the combination of these drugs with hyperthermia demonstrated any significant effect. This method of screening anticancer agents was found to be rapid, simple to perform and inexpensive. PMID- 1615587 TI - Surgical treatment of the atonic bladder ("vesical cap"). AB - As demonstrated in animal experiments and in five patients with atonic bladders, "vesical cap" surgery causally solves detrusor impairment by functionally reinforcing it with a vital muscle layer from an ileal seromuscular flap. All other genuine components of the bladder are kept intact, which is very beneficial for bladder function. PMID- 1615588 TI - Ureterorectal diversion with rectal augmentation. Morphological and manometric study in the dog. AB - Uretersigmoidostomy in the adult has progressively been abandoned because of its high complication rate (both metabolic and functional). We have studied the feasibility of a new model of ureterorectal diversion in 12 Beagle dogs, with the aim of increasing rectal capacity and decreasing rectal pressure. A segment of the ileum was isolated and opened along its antimesenteric border to obtain a patch into which the right ureter was implanted, the left ureter being left intact to allow comparison of the kidneys postoperatively. The patch was then sutured to the edges of a large anterior rectotomy. Modifications of rectal physiology were studied by recording the rectal pressure after distension by a latex balloon both preoperatively and 3 months postoperatively, so that it was possible to evaluate the elasticity of the rectal wall. Radiographic studies and examination of autopsy specimens after 3 months yielded the impression of a reservoir added to the rectal space. Intrarectal pressure was significantly decreased (50% of the preoperative value) for a given distension volume following rectal augmentation (P less than 0.01). The elasticity of the rectal wall was not modified but the capacity of the reservoir was increased. The ureteroileal implantation was patent in two of the five evaluable dogs out of seven implantations performed. In these cases, signs of pyelonephritis were found in the right kidneys. In the remaining cases the implantation became obstructed for reasons mainly related to canine anatomy and experimental conditions. These technical difficulties in the dog make it impossible to assess the quality of this reimplantation technique in this model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615589 TI - [Systemic chemotherapy of urothelial cancer]. PMID- 1615590 TI - [Urologic characteristics of 7 patients over 100 years of age]. AB - In the last few decades the old old have increased continuously in numbers. Diseases of the genitourinary organs are a frequent part of the multiple morbidity we are familiar with in such patients. In the 9th decade of life the renal parenchyma is reduced by 30-50%. The decreased glomerular filtration combined with tubular insufficiency leads to disturbances of the electrolyte, water and acid-base balance. In contrast to these involutionary changes in the kidneys, the prostate increases in size owing to varying degrees of hyperplasia, and the incidence of malignant growth increases progressively. A total of 575 patients over the age of 100 years were observed at the Medical Policlinic of Wurzburg University, and 7 of these who had pronounced urological disorders are described in detail. The variations in the ageing process are considerable. Urological illnesses in the course of the multiple morbidity usual in this group have a particularly unfavourable influence in the terminal phase of these old old patients. PMID- 1615591 TI - [Is ultrasound imaging of the urethra an alternative to radiologic urethral imaging and urethroscopy?]. AB - Ultrasonographic examinations have been widely accepted in urology for a variety of indications. Stimulated by reports on the usefulness of sonourethrography and the idea of reducing radiation exposure, we examined 145 male urethrae during retrograde instillation of sterile saline solution. In addition, 8 patients were examined during spontaneous micturition. We found this procedure to be painless, quick, cheap and to have nearly the same diagnostic value as conventional methods. PMID- 1615592 TI - [Separation of urologic tumors cells from Cell Saver blood using a membrane filter. A new method in autotransfusion?]. AB - Tumor cells of three urological longterm cell lines have been labelled with 35[S] Methionin and added to red cell concentrates. Red cell concentrates rich in tumor cells were passed through a cell saver and two special membranfilters under standard conditions. The 35[S]-Methionin labelled tumor cells were detected by liquid scintillation counting. On an average, only 0.027% of the radioactivity was left after passing through the cell saver and the membran filters in the 12 experiments. If investigations in clinical use of cell-saver and membran filter confirm these results, there will be significant consequences in urological tumor surgery by the possibility of transfusing the salvaged autologous blood. PMID- 1615593 TI - [Correlation of vesico-ureteral reflux and recurrent urinary tract infections with increased bacterial adherence]. AB - Unimpeded urinary flow and voiding of the bladder without residual urine are essential for the prevention of urinary tract infections. Therefore, recurrent urinary tract infections are most commonly found in patients with functional and anatomic disorders of the urinary tract. Children suffering from vesico-ureteral reflux are especially susceptible to recurrent urinary tract infections. The interaction between germ and target cell, i.e. between antigen and receptor, is another important factor in the development of urinary tract infections. This so called bacterial adherence is variable and depends upon receptor density as well as the affinity of the germ to the receptor. However, our study showed that this bacterial adherence plays a minor role in the development of recurrent urinary tract infections secondary to vesico-ureteral reflux. PMID- 1615594 TI - Management of type III stress urinary incontinence using artificial urinary sphincter. AB - Type III stress urinary incontinence due to severe intrinsic urethral weakness without significant urethrovesical descensus may be treated by periurethral injection, sling cystourethropexy, bladder neck reconstruction, or artificial urinary sphincter implantation. The rationale for procedure selection depends on a number of patient factors and the surgeon's experience. We herein report on 25 women who were identified as having such incontinence by evaluation which included videourodynamic study and lateral voiding cystography and who were managed by the implantation of an artificial urinary sphincter. The etiology of the severe intrinsic urethral weakness in most patients was multiple prior failed cystourethropexies. Postoperatively, 1 patient died of a cerebral vascular accident. The remaining 24 women had significantly improved continence and were completely satisfied at latest follow-up. No revisions have been required for patients receiving an artificial sphincter after 1983. No sphincter erosions or infections have occurred. Our experience and review of the literature shows that the artificial sphincter provides an excellent first option for women with type III urinary stress incontinence due to intrinsic urethral weakness of various etiologies. PMID- 1615595 TI - Transurethral incision and posterior resection of prostate (TUI-PRP) for selected patients with benign obstructive prostatic disease. AB - Transurethral incision and posterior resection of the prostate (TUI-PRP) is described and used to overcome my three concerns in performing transurethral incision of the prostate (TUIP). The favorable result from TUI-PRP is presented. PMID- 1615597 TI - Late metastases in seminoma: incidence, localization, and therapeutic implications. AB - Late metastases of seminoma testis were found in 2 patients thirty and nine years after orchiectomy and radiotherapy. Metastases involved retroperitoneal lymph nodes and lung in 1 case and obstruction of the sigmoid colon and left ureter in the other. Cases of late, atypically localized metastases of seminoma described in the literature are reviewed. Therapy includes surgical removal of the metastases, radiation therapy, and systemic chemotherapy. Therapeutic considerations must include toxicity of preceding radiotherapy. PMID- 1615596 TI - Safety of transrectal prostatic biopsy through double-glove technique without antibiotic prophylaxis. AB - We studied 143 men who underwent transrectal prostatic biopsies using the double glove technique. No patient received any antimicrobial therapy before the procedure. Clean catch urine cultures were obtained at admission and two, four, and twenty-four hours, and two weeks after biopsy. Aerobic and anaerobic blood cultures were performed at admission, and at thirty minutes and four hours after the procedure. In addition, clinical parameters were monitored closely in the hospital for twenty-four hours after the biopsy. A total of 132 patients were considered evaluable. Temperatures of 37.6 degrees C or higher occurred in 3.8 percent of the patients. In no case was rigors recorded. In 4 of the patients studied (3%) post-biopsy urine cultures were infected with Escherichia coli. All post-biopsy blood cultures, both aerobic and anaerobic, were negative. Our data indicate that with the use of the double-glove technique, prophylactic administration of antibiotics is not necessary to prevent the infectious complications following transrectal biopsy of the prostate. PMID- 1615598 TI - Renal cell carcinoma: incidental diagnosis and natural history: review of 235 cases. AB - Two hundred thirty-five cases of histologically proved renal cell carcinoma (1976 1987) were reviewed to determine the impact of incidental tumor detection on the natural history of this cancer. One hundred sixty-eight patients (71.5%) presented with clinical signs and/or symptoms of renal pathology. Of these, 25 (18%) were investigated without consideration of renal cell carcinoma in the differential diagnosis. Sixty-seven cases (28.5%) were diagnosed as an incidental finding on diagnostic imaging for extrarenal symptomatology. Approximately 30 percent of patients were found to have metastatic disease on initial presentation regardless of incidental, or suspected discovery of these tumors. Stages A and B tumors were encountered with equal frequency in patient groups with both suspected and incidental diagnosis. Intravenous pyelography was the diagnostic modality used to detect the diagnosis in 83 percent of cases. While incidental detection of renal cell carcinoma has become more frequent than in previous years, it appears to have impacted minimally on the discovery of earlier stage tumors than those with presenting clinical symptoms. In contrast to prior reports, our data show that the natural history of renal cell carcinoma is not significantly altered by the incidental detection of tumor. PMID- 1615599 TI - Ophthalmologic manifestations of genitourinary diseases. AB - There are several urologic disorders which also involve the eye and orbit. We have compiled examples of these and reviewed the literature. Metastasis from genitourinary malignancy (including neuroblastoma), Wilms tumor, Reiter syndrome, tuberous sclerosis, von Hippel-Lindau disease, and oxalosis may all have ophthalmologic manifestations. Urologists need to be aware of these and obtain appropriate consultation in order to fully care for patients with these diseases. PMID- 1615600 TI - Clinical trial of a simplified vacuum erection device for impotence treatment. AB - Thirty-one men participated in a clinical trial of a simplified vacuum erection device (Catalyst) in which the pump and penile cylinder have been combined to facilitate the pumping required to induce a vacuum. Of the 28 men who completed the three-month trial, 26 (93%) reported overall satisfaction with the device and an intention to continue its use, and 2 men were unable to maintain a satisfactory erection. Episodes of mild bruising or development of petechiae occurred in 9 men. None of the complications required treatment or prevented safe use of the device. Our experience with this new vacuum device indicates a high degree of patient satisfaction and minimal complications. On average, patients rated ease of use high at all follow-up visits. PMID- 1615601 TI - Influence of shock waves on fracture healing. AB - During the last decades the influence of physical factors on fracture healing has been widely described. With the use of shock waves for the treatment of urolithiasis, a new mechanical medium has been introduced into medicine. For the first time the influence of shock waves on fracture healing was studied in rats. With fractioned shock-wave treatment (5 times 100 shock waves at 14 or 18 kV) an enhancement in healing could be achieved. PMID- 1615603 TI - Duplicated urethra: an anomaly best repaired. AB - Three cases of urethral duplication are described--two complete and one incomplete. The surgical approaches used in 2 of the 3 cases are described, the third not having come to definitive surgery as yet. In the patient with an incomplete urethral duplication the accessory urethra and associated ventral preputial hood were excised. A repair of the complete duplication was devised in which an end-to-side urethrourethrostomy and penile plastic revision were accomplished. The literature is reviewed and a new classification system for urethral duplication is proposed. PMID- 1615602 TI - Percutaneous pyeloplasty (endopyelotomy) for congenital ureteropelvic junction obstruction. AB - Endopyelotomy was performed in 30 patients with congenital primary ureteropelvic junction obstruction; 4 patients had high insertion of the ureter and 8 patients had caliceal stones. Clinical and radiologic success was achieved in 25 patients. There were five failures, all of whom subsequently had successful open pyeloplasty. The theoretical and experimental foundations of the procedure and fine points of the operative technique are presented. Endopyelotomy appears to be valuable for primary ureteropelvic junction obstruction just as it is for secondary obstruction. PMID- 1615604 TI - Polyorchidism discovered as testicular torsion. AB - We report on a case of polyorchidism that presented as testicular torsion. A brief history and review of the literature is also presented. Of the 47 cases reported, this patient is the youngest. PMID- 1615605 TI - Method for correcting meatal stenosis after hypospadias repair. AB - Meatal stenosis is uncommon after hypospadias surgery even when the meatus is placed at the tip of the glans. However, when it occurs, such stenosis can be quite troublesome. A conventional meatotomy done in the presence of inflammation is often attended by recurrent stenosis. In such situations we therefore advocate placing a tourniquet around the base of the penis and raising a V-shaped flap of glans with the point of the V at the dorsum of the meatus. The stenosis is then incised along the back wall of the urethra down into non-inflamed tissues. The tip of the flap is sutured to this point and additional absorbable sutures are used to anchor the flap in place so that healthy tissue crosses the stenotic area. Recurrent stenosis after this maneuver is unusual. PMID- 1615606 TI - Simultaneous presence of schistosomiasis and advanced cancer in prostate. AB - A forty-nine-year-old patient was found to have Schistosoma eggs inside his prostatic cancer. At the time of diagnosis, the patient already had spread of metastatic disease in lumbar spine. Review of the literature revealed this to be the first such case published in English literature. Despite advanced stage of disease (Stage D2), the patient responded well to immediate orchiectomy and regional irradiation. Two years after diagnosis was established, the patient was without clinical evidence of disease, when he suddenly died. The cause of death was not established because the family declined an autopsy. PMID- 1615607 TI - Filling defect in ureter after ileal conduit surgery. AB - Two cases with a filling defect in the distal part of the ureter after operation with a nippled ureteroileal anastomosis are presented. The filling defects were due to an inversion of the nipple. PMID- 1615608 TI - Use of silicone medical grade tubing for microsurgical vasovasostomy training. PMID- 1615609 TI - Flow cytometric and genetic study of familial gonadal tumors. AB - Three cases of familial gonadal tumors are reported. Genetic studies were conducted in 2 cases: a brother and sister with embryonal carcinoma and a benign cystic teratoma, respectively, and a father and son with embryonal carcinoma. DNA flow cytometry of paraffin-embedded tumors and constitutional karyotyping were performed. Further genetic studies are emphasized. PMID- 1615610 TI - Simple cysts of testis. AB - Three cases of benign intraparenchymal cysts of the testis are described. A nine month-old infant and a forty-two-year-old man were seen with painless testicular enlargement and underwent orchiectomy and cyst excision, respectively. The third patient, a sixty-eight-year-old man, was asymptomatic with the cyst discovered following orchiectomy for prostatic carcinoma. In each case the cyst was multilocular and lined with a simple cuboidal epithelium. In 1 case special and immunohistochemical stains were performed. Review of the literature in conjunction with the cysts' staining characteristics are strongly supportive of its derivation from ectopic epithelium. PMID- 1615611 TI - Renal scintigraphy in initial evaluation of renal colic. AB - To determine the role of renal scintigraphy (RS) in patients with suspected acute urinary tract obstruction, a prospective study was performed comparing RS with emergency intravenous excretory urography (IVU) in 36 examinations. Thirty patients were diagnosed as having renal colic: 28 had dilation of the urinary tracts with (89%) or without (11%) visualized stone; 2 patients with stones did not have stasis at the IVU. An abnormal RS was found in 28 patients with abnormal IVU, while it was normal in the 2 nonobstructed patients (sensitivity = 93%). The radiopaque stones in these 2 patients were seen on plain x-ray film of the abdomen. The results of this study support the use of RS combined with a plain film of the abdomen in the initial evaluation of renal colic. PMID- 1615613 TI - Varicocelectomy: incidence of external spermatic vein involvement in the clinical varicocele. AB - The vascular anatomy of the clinical varicocele, and the incidence of involvement of the external spermatic vein were studied. Dilation of the external spermatic vein (4 mm) was found in 49.5 percent of 93 varicoceles in 67 patients. The location of this vein, its potential involvement in a varicocele, and its management were reviewed. PMID- 1615612 TI - A seventy-eight-year-old man with flank pain. PMID- 1615614 TI - Experience with weekly doxorubicin (adriamycin) in hormone-refractory stage D2 prostate cancer. AB - One hundred eleven patients with endocrine-refractory Stage D prostate cancer were treated with weekly administration of 20 mg/m2 body surface area of doxorubicin hydrochloride (Adriamycin). Fifty-seven were part of a randomized study comparing doxorubicin and prednisone to prednisone alone. There were significantly more subjective responders in the doxorubicin group than in the prednisone group (p less than 0.01). The number of patients with evidence of stable disease was also higher during the chemotherapy arm compared with prednisone alone (p = 0.02). Patients taking doxorubicin had a slightly longer period of stable disease than did those taking prednisone (p = 0.08). Overall survival, however, was not prolonged (p = 0.26). Fifty-four patients took part in an open trial and 69 percent responded to treatment. All of these had clinical improvement. Side effects were minimal with cardiotoxicity noted in less than 15 percent among patients with side effects. Over 35 percent had no side effects. Thus single agent, weekly doxorubicin therapy as evaluated in our experience, while well tolerated and of subjective benefit, does not provide the patient with a significant longer progression-free survival or improved overall survival. PMID- 1615615 TI - Antibiotic prophylaxis following lower urinary tract instrumentation. AB - The value of routine antibiotic prophylaxis was assessed in 362 women undergoing lower urinary tract instrumentation. A three-day course of a once-a-day dose of 1 g of cefadroxil was compared with a three-day course of 100 mg of nitrofurantoin three times a day, in a randomized investigator blinded placebo controlled study. Both study drugs were significantly more effective in preventing postinstrumentation urinary tract infections than placebo (p less than 0.003). Differences in efficacy between the two test drugs were not significant; however, side effects in the nitrofurantoin group were more frequent and severe than those in the cefadroxil group. Cefadroxil also offered the advantage of a once-daily dosing schedule. PMID- 1615616 TI - Subsistence insecurity and ill feeling in domiciliary care. AB - The purpose of this study was to analyse the relationship between the feeling of subsistence security and well feeling. For the study 129 patients in Helsinki domiciliary care were interviewed. Relationships between subsistence security and well feeling have been demonstrated by chi-square test. According to the findings physical, mental and social well feeling decreased when financial difficulties increased. Experienced improvement in health was less for those patients who had financial difficulties than for those who had not. The subsistence security was the main predictor of the variances of the sumvariables 'physical well-ill feeling' and 'mental and social well-ill feeling'. It can be suggested that for indigent people in domiciliary care it is not sufficient that a variety of services is available. It is therefore an important task of the nurses to strengthen the indigent patients' ability to utilize the different opportunities available in order to improve their well feeling and ability to cope at home. PMID- 1615617 TI - [Gender variables in nursing theories. A text analysis of 5 theories]. AB - During individual care planning in the education of nurses, the students learns to plan, carry out and assess care on the basis of nursing theory. Neutral terms such as patient, client, individual and person commonly occur in planning. The level of personalization can not, however, be considered satisfactory if no attention is paid to gender related variables and if differences in the reaction of men and women to problems and illnesses are not underlined. The aim of the study was to investigate if and how gender related aspects appear in nursing theories. The book "Nursing theories--the base for professional nursing practice" was used as the primary source for the choice of theorists. From the initial selection (n = 12) the five most quoted theorists according to Nursing citation index 1988-1989 (Orem, Rogers, Roy, Nightingale och Peplau), were studied. The result shows that little attention is paid to the gender perspective of patients. Consequently needs of differentiation between women and men are imperfectly observed in individual care planning. PMID- 1615618 TI - [Delimitation of the biomedical models and its consequences for the holistic viewpoint in nursing, and for quality research]. AB - Medicine is dominated today by the so called biomedical model of sickness. This model ontologically reduces Man to biochemistry and every kind of sickness to disease, and therefore expresses an ontologically reductionistic view of Man. This view is logically incompatible with the humanistic view of Man, and a holistic concept of health. Given the distinction between disease and illness, the model is in most cases necessary and sufficient for the treatment of disease but for certain kinds of illness it might be neither necessary nor sufficient. In order to be a fruitful model it should be radically changed so that it can be supplemented by models based on a humanistic view of Man and a holistic concept of health. A complementary model would have positive effects on medical praxis, health care in general and on the Science of Health Care. PMID- 1615619 TI - The models of nursing activity in the basic care of demented patients living in institutions. AB - The chief concern of this article is the basic care of demented patients living in institutions. The data for the study were collected by observing basic care situations and interviewing practising nurses. The analysis was based on continuous comparative analysis. Five models of nursing activity were identified: rejective, routinized, robot-like, cassette-like, and skillful. Nurses concentrated more on obligatory daily activities than on the individual needs of demented patients, on the special characteristics of dementia, or on encouraging spontaneous activity among demented patients. The nurses tended to look at demented patients chiefly in terms of the abilities they had lost and the disturbance they caused; less attention was given to their remaining facilities, such as their sense of humor and their ability to enjoy things and to establish contact through gestures and physical touching. PMID- 1615620 TI - Subjective loneliness--a comparison between elderly and relatives. AB - The survey was aimed at examining the differences between the elderly's subjectively experienced loneliness and relatives' appraisal of the situation. The interviews contained structured questions about relatives' knowledge of the elderly's loneliness and their social contacts with the elderly. In total, 178 relatives took part in the interviews. The Cognitive-impaired group included 66 pairs elderly/relatives, where the elderly persons were cognitively impaired, and the Cognitive-intact group 112 pairs, where the elderly persons had normal cognitive function. There were differences between relatives' appraisal of loneliness and the elderly's own experience. The elderly with cognitive deficits seemed to feel loneliness more often than persons with intact cognitive ability. Relatives tended to overestimate the elderly's loneliness, especially among persons with cognitive difficulties. These elderly more often had short frequent visits, while persons in the Cognitive-intact group had longer, but not so frequent visits. PMID- 1615621 TI - Invited article: Richard D. Turk Memorial Lecture--parasites' progress. AB - The College of Veterinary Medicine at Texas A & M University celebrated its 75th anniversary in September 1991. As a part of this celebration, Professor Lord Soulsby was invited by the faculty of the Department of Veterinary Pathobiology to deliver the annual Turk Memorial Lecture. The following is Professor Lord Soulsby's presentation. PMID- 1615622 TI - A survey of ovine parasite control practices in Tennessee. AB - A sample of 126 sheep producers in Tennessee was randomly selected from the members of a statewide organization of sheep producers. Data about the participants' farms, sheep, parasite control practices and sources of information regarding ovine parasite control were obtained by a telephone survey. The response rate was 99%. The typical respondent kept 20 lambs, 20 ewes and 2 rams on three pastures totalling 20 acres. In order of decreasing frequency, anthelmintics were given according to a regular schedule, to coincide with breeding management procedures, or to treat clinical signs of parasitism. Proportions of producers deworming the various classes of sheep zero, one, two, three, four or more than four times annually were as follows: lambs--3, 28, 40, 16, 9 and 8%, respectively; ewes--3, 8, 20, 16, 34 and 22%, respectively; rams- 1, 9, 19, 15, 38 and 19%, respectively. The majority of respondents planned to deworm lambs (89%) and ewes (82%) the same number of times in the following year. Of the producers who dewormed sheep two or more times during 1989, 39-49% (ranges include different proportions for lambs, ewes and rams) used the same anthelmintic exclusively, and 51-61% used two or more drug classes. Of the owners using a single anthelmintic exclusively, most (39-66%) used ivermectin, followed by levamisole (19-33%) and benzimidazoles (13-24%). One hundred and three of 124 (83%) producers intended to use the same anthelmintics in the future. Sixty-four of 124 (52%) producers had discontinued using at least one ovine anthelmintic. The most common reasons for discontinuance were dissatisfaction with the clinical response after treatment and inconvenience of administration. Sheep-oriented publications, other sheep producers and veterinarians were considered the most important sources of information about deworming programs and choice of anthelmintics. PMID- 1615623 TI - Laboratory and field observations on anti-tick properties of the plant Gynandropsis gynandra (L.) Brig. AB - A shrubby plant, abundant in east Kenya, Gynandropsis gynandra (L.) Brig., was shown to exhibit repellent and acaricidal properties to larvae, nymphs and adult Rhipicephalus appendiculatus and Amblyomma variegatum ticks. All stages of ticks avoided the leaves of the plant and a high percentage of the ticks which were continuously exposed to its leaves died; surviving ticks were weak and inactive but regained activity when exposed to fresh air. The effectiveness of the plant's leaves as a repellent and acaricide was most pronounced on nymphs and least pronounced on adults. Field investigations indicated that ticks were not found up to 2-5 m from the plant in areas where the plant was predominant. The potential of using the plant for tick control within an integrated tick management system in the resource-poor farming context in Africa was highlighted. PMID- 1615624 TI - Analytical determination of the distribution of flumethrin on the body surface of cattle following topical pour-on application. AB - By means of chemical analysis, the distribution behaviour of flumethrin was determined in the hair coat of cattle following topical pour-on application. Flumethrin was applied at 1 mg active ingredient (a.i.) kg-1 body weight along the backline of cattle. It was demonstrated that this compound could be recovered from all hair samples taken on Day 1 following application from dorsal, lateral, ventral and distal body regions in concentrations ranging from 670 to 1 micrograms a.i. g-1 hair, depending on the distance from the site of application. On Days 3, 5 and 10 after treatment, the corresponding concentrations were 125.0 1.5, 23.0-1.0, and 44.0-0.9 micrograms a.i. g-1 hair, respectively. When correlating these values to the body surface of cattle, it is evident that on all sample days and body regions, a concentration of more than 0.01 microgram a.i. cm 2 body surface was present. This amount of active substance is sufficient for effective acaricidal action, as shown by laboratory and field data. PMID- 1615625 TI - Development of an enzyme-linked immunosorbent assay (ELISA) for the detection of antibody to the parasitic dinoflagellate Amyloodinium ocellatum in Oreochromis aureus. AB - An enzyme-linked immunosorbent assay (ELISA) using antibody to affinity-purified Oreochromis aureus immunoglobulin and antigens from the parasitic dinoflagellate amyloodinium ocellatum was developed. The ELISA was then used to evaluate the immune response of the tilapine fish to immunization with the parasite. Fish immunized with antigens of the dinospore stage, either live or sonicated, produced a specific immune response that was detectable by this ELISA. Combinations of serial dilutions of A. ocellatum antigen and fish anti-A. ocellatum serum were examined to determine which dilutions provided optimal differentiation of seropositive from seronegative fish. Fresh and heat inactivated serum from both seropositive and seronegative fish produced similar results. PMID- 1615626 TI - Adrenal and thyroid dysfunctions in experimental Trypanosoma congolense infection in cattle. AB - Severe pathological changes were observed in the adrenal and thyroid glands of Zebu (Bos indicus) heifers infected with Trypanosoma congolense. In the adrenal glands, severe inflammatory changes characterised by mononuclear cellular infiltration in the subcapsular areas, zona glomerulosa, zona fasciculata and zona reticularis were observed. In addition, there were hyperaemia, haemorrhage and hyperplasia resulting in increased adrenal weight in the two heifers slaughtered on Days 50 and 70 post-infection (p.i.). In the medullary areas of these two heifers, there was only mononuclear cellular infiltration. In the two heifers slaughtered on Day 113, localised mononuclear cellular infiltration was observed in addition to cortical cell depletion and fibrosis, resulting in reduced adrenal weight when compared with the controls. In the thyroid glands of the infected heifers, gross enlargement of the follicles filled with pale staining colloids were observed in association with squamous metaplasia of the follicular epithelium and fibroplasia. Serum cortisol concentrations showed an appreciable but non-significant increase (P less than 0.05) between Weeks 2 and 6 p.i. in the infected heifers (5.6 +/- 0.86 ng ml-1 vs. 4.4 +/- 0.34 ng ml-1) when compared with the uninfected controls or the pre-infection level. Thereafter, cortisol levels declined though non-significantly throughout the rest of the study. However, there was a steady increase towards normal levels from Week 12 p.i. until the end of the experiment. Changes in the basal serum concentrations of thyroxine (T4) were also measured weekly. There was a progressive decrease in the levels of T4 from the third until the 11th week p.i., when the decrease became significant (P less than 0.05) and remained so until the 16th week when the experiment ended. PMID- 1615627 TI - Seasonal variation of oribatid mite (Acarina) populations and their relationship to sheep cestodiasis in Argentina. AB - Samples of soil were collected monthly from two ranches in the zone of Puan, Province of Buenos Aires, Argentina. The monthly distribution of males, females without eggs and females with eggs for the dominant species of oribatid mites were studied. The dominant species were Zygoribatula lata in Ranch A, and Zygoribatula elongata in Ranch B. Both species are hosts of Moniezia expansa Rudolphi, 1810 and Helictometra giardi Baer, 1927. Based on the data presented, the factors associated with transmission of these cestodes, including the role played by oribatid mites, are discussed. PMID- 1615628 TI - Seasonal variations in the numbers of trichostrongylid nematode eggs and their larvae in the faeces of farmed goats in Malaysia. AB - Faecal worm egg counts of goats from two farms in Penang Island, West Malaysia, were monitored over a period of 14 months. The faecal egg count pattern followed that of total rainfall. The humid tropical environment was favourable for the development of various species of trichostrongylid nematodes, namely Haemonchus contortus, Trichostrongylus spp., Oesophagostomum spp. and Cooperia spp. Generally, H. contortus was observed to be the predominant species, more so in the monsoon months of the year. PMID- 1615629 TI - In vitro multiplication of Cryptosporidium parvum in mouse peritoneal macrophages. AB - Cryptosporidium parvum of bovine origin was developed in vitro in unsensitized mouse peritoneal macrophages. Macrophages growing in RPMI medium were infected with sporozoites or with oocysts, and after staining infections were studied by light microscopy. A high parasitic index was obtained with multiple infections occurring commonly. This is a simple method for the study of Cryptosporidium biology, and for in vitro assays of pharmacological activity. PMID- 1615630 TI - Lipid metabolism and Sarcocystis miescheriana infection in growing swine. AB - Sixteen 2-month-old pigs were divided into four equal groups and infected with either 500,000, 1,000,000 or 3,000,000 sporocysts of Sarcocystis miescheriana. Four pigs served as uninfected controls. Pigs were bled weekly and serum was collected beginning 14 days prior to infection and continuing until 63 days after infection. Body fat composition, as measured by the specific gravity of the carcass, was not affected by infection. There were no significant effects of infection on serum concentrations of glucose, insulin, triglycerides, and total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol. A slight depression in HDL cholesterol occurred during the acute phase of infection. Tumor necrosis factor (TNF) was not detected in serum from infected swine when assayed by a cytotoxicity assay using TNF-sensitive WEHI 164 clone 13 cells. Attempts to stimulate TNF production in RAW 264.7 cells with parasitic lysates gave mixed results. This study suggests that the disruption of lipid metabolism is not the primary cause of growth retardation in growing swine infected with S. miescheriana. PMID- 1615631 TI - The efficacy of ivermectin against Thelazia rhodesii (Desmarest, 1828) in the eyes of cattle. AB - One hundred cattle with confirmed natural infections of Thelazia rhodesii were included in three studies to evaluate the efficacy of ivermectin for the treatment of eyeworm infection. Thelazia rhodesii were counted in situ in each eye of each animal on Day 0 (prior to treatment) and the cattle were paired by the number of worms, within categories of sex, age or number of infected eyes. Within each pair, one animal was randomly assigned to serve as an untreated control, while the other was treated subcutaneously with ivermectin at 200 micrograms kg-1 body weight. Eight days later, parasites were recovered from each eye separately, identified and counted. In each study, significantly (P less than 0.01) fewer T. rhodesii were collected on Day 8 from ivermectin-treated cattle than from controls. Overall, the reduction in numbers of T. rhodesii collected from treated cattle was greater than 99% (P less than 0.05) relative to controls, with reductions of 100% being recorded in two of the three studies. PMID- 1615632 TI - Epidemiology and effects of nematode infections on beef cow-calf systems of Argentina's western pampas. AB - The epidemiology and the effects of nematode infections on cow-calf systems were followed from 3 weeks before calving to 7 months afterwards. Two groups, each of 15 cow-calf pairs grazed on separate lucerne pastures. Group I (GI) were treated monthly with oxfendazole (4.5 mg kg-1), cows being dosed from calving and calves starting 45 days later. Animals in Group II (GII) were not treated. The egg output of the cows was very low. An increase was recorded 2 months after parturition, consisting mainly of Ostertagia spp. The egg output and worm burdens of calves remained low until late summer and reached a peak in autumn. Ostertagia, Cooperia and Haemonchus were the main genera recovered from slaughtered calves. The pasture contamination and tracer calf worm counts remained consistently low until autumn when they began to increase. Inhibited early fourth stage larvae of Ostertagia were recovered during spring. After calving, the live-weight gains (LWG) of treated GI cows were significantly higher (P less than 0.004) than those of GII cows, whereas the LWG of GI calves were significantly higher during December (P less than 0.037) and March (P less than 0.029) than those of GII calves. There were significant (P less than 0.04) cumulative LWG responses between GI and GII calves with no differences in cow cumulative LWG at the end of the trial. For spring-born calves, these results suggest that strategic deworming programs in cow-calf systems may produce benefits. PMID- 1615633 TI - Immune responses of pony foals during repeated infections of Strongylus vulgaris and regular ivermectin treatments. AB - Ten helminth-free pony foals divided into three groups were used in this study. Eight foals were each experimentally infected per os with 50 Strongylus vulgaris infective larvae weekly for 4 weeks, at which time one foal died of acute verminous arteritis. The remaining seven foals subsequently received 50 S. vulgaris infective larvae every 2 weeks for an additional 20 weeks. Four of the infected foals remained untreated (Group 1) and three of the infected foals were given ivermectin at 8, 16 and 24 weeks post initial infection (Group 2). Two foals served as controls (Group 3). Foals in Group 1 developed eosinophilia, which was sustained throughout the course of infection. A mild eosinophilia also developed in Group 2 foals; however, the eosinophil numbers were markedly reduced for 3 weeks after each ivermectin treatment. Only foals in Group 1 developed significant (P less than 0.05) hyperproteinemia, hyperbetaglobulinemia and a reversal of the albumin/globulin (A/G) ratio 4 weeks after initial infection. Significant (P less than 0.05) IgG anti-S. vulgaris ELISA titers developed in foals in Groups 1 and 2 3 weeks after infection and were sustained for the duration of the experiment. Western blot analysis of soluble somatic antigens of S. vulgaris adult female and male worms probed with sera from foals in Groups 1 and 2 revealed only subtle differences between these animals. The blastogenic reactivity of peripheral blood mononuclear cells (PBMC) to phytohemagglutinin and concanavalin A was not significantly different between groups. Peripheral blood mononuclear cells from foals in Groups 1 and 2 developed significant (P less than 0.05) blastogenic reactivity to S. vulgaris soluble adult somatic antigen when examined at 25 weeks after infection. Mesenteric lymph node cells from foals in Group 2, although not statistically significant, were more reactive to antigen than were the mesenteric lymph node cells from foals in Group 1 when examined at 27 weeks after infection. These results suggest that significant alterations in the immune response of ponies to S. vulgaris does not occur after intravascular killing of larvae by ivermectin treatments. PMID- 1615634 TI - An attempt to define the host range for African horse sickness virus (Orbivirus, Reoviridae) in east Africa, by a serological survey in some Equidae, Camelidae, Loxodontidae and Carnivore. AB - A survey was carried out in horse, zebra, elephant, camel, sheep and goat and wild carnivore sera for virus-serum neutralising antibody to the nine type strains of African horse sickness virus. Antibody was found amongst the horse, zebra and elephant sera to all nine different strains. No antibody was detected in any sera from camels, sheep and goats. None was found in sera from hyaena and jackals in this series but had been detected earlier. PMID- 1615635 TI - Serodiagnosis of leptospirosis in pigs using an axial filament enzyme-linked immunosorbent assay. AB - The axial filament (AF) from Leptospira interrogans serovar canicola was isolated by cesium chloride density gradient centrifugation of 2% sarcosyl treated whole cells. Isolation of AF was confirmed by electron microscopic examination, by protein-A immunogold labelling, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), and immunoblotting. Analysis by SDS-PAGE of the purified preparation showed relatively weak bands of molecular size 41 kDa and 21 kDa, and strong bands of 35 kDa and 34.5 kDa. Immunoblot analysis using antiserum to the AF against sonicated leptospires of a variety of serovars showed prominent reaction against the 41, 35, and 34.5 kDa protein bands, as well as against minor bands of molecular weight 43, 39, and 37 kDa. Antisera prepared against leptospiral serovars also identified minor bands at 33 and 32 kDa. Immunoblots with antiserum to whole cells of serovar bratislava detected the 35 and 34.5 kDa AF bands of Borrelia burgdorferi moderately and of Treponema hyodysenteriae only slightly in comparison to leptospiral AF. Antibody to B. burgdorferi did not detect the leptospiral AF antigen. Immunoblots with antiserum to T. hyodysenteriae showed a marked reaction with a 41 kDa band of B. burgdorferi but only a very minor reaction with leptospiral AF. The AF was tested in an AF-ELISA against sera from 260 pigs, many of which reacted in the microscopic agglutination test (MAT) against one or more leptospiral serovars. A sensitivity of 97.1% and a specificity of 93.1% was determined in comparison to the MAT. Only moderate correlation was observed between titres detected in the AF-ELISA and the MAT (r = 0.4). When sonicated whole cells (WC) of serovar canicola were used in an ELISA (WC-ELISA), high correlation was observed between AF-ELISA and WC-ELISA (r = 0.97). These findings show that the AF-ELISA can be used effectively as a species-specific antigen for the serological diagnosis of leptospirosis in swine and that sonicated whole cells can substitute excellently for purified AF as the antigen source. These findings may be extrapolated to the use of AF in immunodiagnosis of leptospirosis in other species. PMID- 1615637 TI - The effect of oxytetracycline treatment on immunity induced by Anaplasma centrale. AB - Calves vaccinated with Anaplasma centrale were treated with 20 mg/kg of long acting oxytetracycline (OTC/LA) before or simultaneously with vaccination or up to seven months later. Of 40 animals given one or two of OTC/LA from 3 to 13 days before vaccination, 23 become patent after vaccination, with an average prepatent period almost twice as long as that in non-treated vaccinated controls. Upon challenge with 2 x 10(8) A. centrale per dose all 17 previously non-patent calves showed average maximum parasitemias of 2 to 3.8%. Out of 30 calves treated with two to four doses of OTC/LA from one to four weeks after vaccination, 29 remained negative for A. centrale and reacted to challenge infection with average maximum parasitemias of 6.9-7.8%. Five out of 10 calves receiving OTC/LA simultaneously with the vaccination, and all of a separate group of 10 calves treated with a single dose seven days after vaccination, become patent an average of 51.6 and 63.5 d, respectively, after vaccination. Upon challenge, the five previously non patent calves showed an average of 5.2% maximum parasitemia. In all groups, only rare parasites were seen in previously patent calves after challenge. Thirty calves treated with 2-4 doses of OTC/LA about six months after vaccination showed no or only a few parasites upon challenge. The above results show that treatment with single or multiple doses of OTC/LA a few weeks before or after administration of live A. centrale vaccine can interfere with elaboration of immunity. PMID- 1615636 TI - A field evaluation of serological and cellular diagnostic tests for bovine tuberculosis. AB - This paper describes the field evaluation of a serological test and a new in vitro assay for cell-mediated reactivity for the diagnosis of bovine tuberculosis. The use of a Mycobacterium bovis-specific antigen (MPB-70) in an ELISA to test the serological response to tuberculosis infection resulted in a specificity of 96.4% and a sensitivity of 18.1%. The most favourable results were obtained with the interferon gamma (IFN-gamma) assay which had a sensitivity of 81.8% and a specificity of 99.1%. Respective figures for the single intradermal tuberculin test were 68.1% and 96.7%. The use of MPB-70 as the antigen in the IFN gamma assay reduced the sensitivity of this assay, without producing any useful increase in specificity. The IFN-gamma assay was also demonstrated to be a practical diagnostic test for use with large groups of cattle. PMID- 1615639 TI - OSHA rules on bloodborne pathogens. PMID- 1615638 TI - Development of double sandwich ELISA for Clostridium perfringens beta and epsilon toxins. AB - Specific, double-sandwich ELISAs for beta and epsilon toxins were developed by coating wells of microplates with specific sheep antitoxin IgG and using specific rabbit antitoxin IgG as detecting antibodies. The assay for beta toxin detected a minimum level of 8 ng/ml of purified toxin. The assay for epsilon toxin was capable of detecting 2 ng/ml of purified toxin. When applied to detect the toxin in intestinal contents using 50% fetal bovine serum as diluent the lowest amounts detected were about at least 30 ng/ml for beta toxin and 4 ng/ml for epsilon toxin. Clear differences in ELISA readings of both assays have been found between culture filtrates from toxin and non-toxin producing strains. These results suggested that both assays described in this study could detect their respective toxin in buffers, culture supernatants or in intestinal contents. PMID- 1615640 TI - The supply of mammography resources in West Virginia. AB - The distribution of mammography machines and related resources in West Virginia, along with the distribution of breast cancer screen-eligible women, are examined using county-specific data. This data placed on a state map shows that it is not necessary to cross more than one county line anywhere within West Virginia in order to visit a mammography facility. The overall density of these machines is 20 per 100,000 women over 45, almost double the capacity needed for screening mammography. After taking into account the projected demand for mammography, the current average cost per exam is around $65-$100. If mammography machines were placed in all the counties without machines, the cost in those countries would be around $140 per exam. It would be cheaper to provide a travel allowance to women in rural counties than to install machines in these areas. Machines that are accredited by the American College of Radiologists, the most available indicator of quality mammography, are located only in densely populated areas of the state. PMID- 1615641 TI - Critical incident stress in prehospital emergency care. AB - In addition to the routine pressures associated with their demanding roles, prehospital emergency responders can suffer severe stress as a result of exposure to a critical incident. Such an event overwhelms the individual's ability to emotionally adjust, and can lead to symptoms which cause suffering in emergency personnel, their families and their patients. A Critical Incident Stress Management (CISM) Team has been established in southern West Virginia to address this occupational hazard. This group was formed as a cooperative arrangement between the Charleston Division of the West Virginia University Health Sciences Center and emergency personnel in the Greater Kanawaha Valley. This article offers an explanation of the team's functioning and specific information regarding its activation. PMID- 1615643 TI - The family. PMID- 1615642 TI - A patient with eosinophilia, hypoalbuminemia and abdominal pain. AB - Strongyloides stercoralis infections frequently present with eosinophilia and abdominal pain. Since the gastrointestinal symptoms are non-specific, only 15 percent of these patients are correctly considered to have an infectious enteritis or intestinal parasite. In fact, the initial diagnosis is peptic ulcer disease in most patients. The clinical course may be indolent, or patients may develop a sudden catastrophic illness, particularly following the administration of corticosteroids. PMID- 1615644 TI - Autonomy versus do no harm. PMID- 1615645 TI - Anxiety among Cambodian refugee adolescents in transit and in resettlement. PMID- 1615646 TI - Self-efficacy and social support in self-management of epilepsy. PMID- 1615647 TI - Using NCAST instruments with urban American Indians. PMID- 1615648 TI - How married couples make decisions. PMID- 1615649 TI - Construing benefit from a negative experience of incest. PMID- 1615650 TI - Measuring circadian rhythms. Actigraph Versus Activation Checklist. PMID- 1615651 TI - Nurse moral reasoning using the Nursing Dilemma Test. PMID- 1615652 TI - Ethical considerations for quality assurance versus scientific research. AB - There is increasing evidence to support the contention that the boundaries between QA and scientific clinical research are blurred. This blurring is of particular concern in relation to the protection of human subjects rights (Brett & Grodin, 1991). The article thus concludes that it is essential that proposals for QA programs undergo periodic appraisal by an institutionally responsible, disinterested review panel. It further concludes that it is essential to submit proposals for all prospective QA projects, potentially scientifically meritorious QA projects, and all scientific clinical research projects to an institutional review board (IRB) to render decisions about the protection of human subject's rights before accessing data. Doing so protects the subject's rights, protects the investigator from unwittingly rendering harm rather than good, and enhances the ethical credibility of the projects. It also protects the investigator from embarrassing and potentially litigious situations. It is also incumbent on IRBs to develop efficient, effective, and expeditious review processes that encourage rather than discourage the a priori review process. PMID- 1615653 TI - Design and measurement challenges in family research. AB - Closing the chasm between family theory, nursing practice, and family research requires design and methods that foster the study of families as dynamic, holistic entities. This article has outlined several strategies for capturing morphostasis and morphogenesis and for studying the family as a unit of analysis. PMID- 1615654 TI - Clinical training in human immunodeficiency virus disease for community physicians. The Los Angeles experience. AB - In the past decade, the increased number of persons being treated for infection with the human immunodeficiency virus (HIV) has placed an enormous burden on specialty clinics. This is especially true in Los Angeles, where care of patients with the acquired immunodeficiency syndrome (AIDS) has been termed a "crisis" situation. Especially in its early stages, HIV disease can be appropriately managed by primary care physicians who provide patients with medical and psychological counseling and refer them to specialists when major AIDS-related complications develop. Physicians completing their training as recently as 5 years ago, however, received little systematic preparation in the care of HIV infected patients and thus may lack important skills such as the ability to recognize opportunistic infections early in their course. By means of a 1-week intensive preceptorship in a high-volume AIDS clinic, we are preparing community physicians to assume a more active role in providing care for this growing patient population. In the preceptorship, participants receive one-on-one training from specialists in infectious diseases, pulmonary diseases, and hematology and oncology, as well as from internists and family physicians. Evaluation of the clinical experience demonstrated a greater level of confidence on the part of program participants in treating HIV-infected patients and showed that participants screen and test high-risk patients in their practices and devote a substantial proportion of their practices to caring for HIV-infected patients. PMID- 1615655 TI - Adolescent health care in a large multispecialty prepaid group practice. Who provides it and how well are they doing? AB - Adolescents are at risk for pregnancy, sexually transmitted diseases, suicide, homicide, accidents, and substance abuse. Adolescent medicine involves an overlap of many skills needed to provide routine medical care, as well as care for those conditions that require psychosocial assessment. We report the results of a mail survey covering care of this age group by practitioners of pediatrics, internal medicine, obstetrics and gynecology, family practice, and adolescent medicine in a large, multispecialty, prepaid group practice. The mail survey covered 10 areas of adolescent care. Adolescent medicine physicians expressed the highest level of perceived knowledge and competence in these areas, with family practitioners ranked second. More than 50% of internists and pediatricians felt only fair to poor competence for a variety of adolescent conditions, whereas a third of internists and pediatricians reported that they liked to care for adolescents. Physicians in all 4 of the primary care specialties reported a need for a teen health center for both consultation and education. These results are similar to those reported for pediatricians and primary care physicians in private practice and for residents in internal medicine. PMID- 1615656 TI - Drug dosing guidelines in patients with renal failure. AB - The metabolism and excretion of many drugs and their pharmacologically active metabolites depend on normal renal function. Accumulation and toxicity can develop rapidly if dosages are not adjusted in patients with impaired renal function. In addition, many drugs that are not dependent on the kidneys for elimination may exert untoward effects in the uremic milieu of advanced renal disease. A familiarity with basic pharmacologic principles and a systematic approach are necessary when adjusting drug dosages in patients with abnormal kidney function. The distinct steps involve calculating the patient's glomerular filtration rate, choosing and administering a loading dose, determining a maintenance dose, and a decision regarding monitoring of drug concentrations. If done properly, therapy in renal patients should achieve the desired pharmacologic effects while avoiding drug toxicity. Physicians must not oversimplify the pharmacologic complexities presented by patients with renal failure by relying excessively on nomograms and "cookbook" equations. In addition to a reduced glomerular filtration rate, patients with renal disease often have alterations in pharmacokinetics such as bioavailability, protein binding, hepatic biotransformation, and volume of distribution. An awareness of biologically active or toxic metabolites of parent compounds that accumulate when the glomerular filtration rate is reduced is also necessary to avoid toxicity. The effects of dialysis on drug elimination and the need for supplemental dosing are additional considerations in patients undergoing renal replacement therapy. PMID- 1615657 TI - Diabetes mellitus in pregnancy. AB - The Council on Scientific Affairs of the California Medical Association presents the following inventory of items of progress in obstetrics and gynecology. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. 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, or scholars to stay abreast of these items of progress in obstetrics and gynecology that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on Obstetrics and Gynecology of the California Medical Association, and the summaries were prepared under its direction. PMID- 1615658 TI - RU 486 (mifepristone). PMID- 1615659 TI - Management of hirsutism. PMID- 1615661 TI - Substance abuse in pregnancy. PMID- 1615662 TI - Premenstrual syndrome. PMID- 1615660 TI - Who is a candidate for Norplant? PMID- 1615663 TI - Genetic predisposition to ovarian cancer. PMID- 1615664 TI - Ovarian cancer screening. PMID- 1615665 TI - Secondary syphilis presenting as nephrotic syndrome. PMID- 1615666 TI - Seat belt use during pregnancy. PMID- 1615667 TI - Reexpansion pulmonary edema in AIDS. PMID- 1615668 TI - Drug company marketing in the groves of academe. PMID- 1615669 TI - Noninvasive monitoring of oxygenation and ventilation. 40 years in development. PMID- 1615670 TI - Practical therapeutics in patients with renal impairment. PMID- 1615671 TI - Autoimmune disease and the nervous system. PMID- 1615672 TI - Tic or dystonia? PMID- 1615673 TI - Nintendo elbow. PMID- 1615675 TI - [The male climacteric from the practical viewpoint]. AB - A transient physiologic period similar to that in women leads from full sexuality to senium in the life of men, too. This phase may involve the complex of male climacteric symptoms. The diminished testosterone secretion of the testes as endocrine "primum movens", together with an increased level of the carrier protein (SHBG), results in a reduced androgen supply of the organism, as reflected in a low free andorgenic index. The diagnosis of male climacteric is made on the basis of an enhanced serum LH level. With regard to the differential diagnosis, atherosclerosis, diabetes mellitus, chronic alcoholic liver damage, malignant tumors and prostatic complaints are particularly to be considered. The hormonal treatment consists of low-dose testosterone medication; for the prevention of osteoporosis, however, testosterone preparations may be replaced by anabolic steroids. As for women, the concomitant vegetative phenomena of the climacteric syndrome should be alleviated symptomatically. PMID- 1615674 TI - Primary care professionals' attitudes regarding compulsory HIV testing. PMID- 1615676 TI - [Psychological disorders of menopause: on the topic of multifactorial origin]. AB - Interdisciplinary scientific research is an unjustly neglected discipline in the investigation of etiology and therapeutic potential regarding the symptoms of pre , peri- and postmenopause. Thus the aim of this paper is: 1) the description of psychological disturbances occurring before, during and after menopause, 2) a representation of the etiological interaction between endocrinological, vegetative, psychodynamic and psychosocial factors of influence, and 3) to summarize the possible psychiatric and psychotherapeutic measures which can be taken. PMID- 1615678 TI - [Contraception in climacteric]. AB - The problems of an adequate contraception around the age of 40 are not yet solved in our time. On one hand the women are afraid of unexpected pregnancies during this life period, at the other hand the hormonal contraceptives are not anymore optimal at this time. The various contraceptive methods with its positive and negative effects during this period are discussed in this paper. PMID- 1615677 TI - [The atheroprotective importance of estrogen substitution from the social medicine viewpoint]. AB - Due to the increasing life expectancy most women nowadays suffer from menopausal problems. These include not only menopausal symptoms, but also osteoporosis and atherosclerosis. Hormone replacement therapy therefore is a measure for keeping physiological standards. It has both preventive and therapeutic importance, for the individual as well as for the public. In the following we give an overview to these aspects, focusing on prevention of atherosclerosis. PMID- 1615679 TI - [Gyneco-urologic problems in climacteric]. AB - In climacteric women stress and urge incontinence often occur as a consequence of estrogen deficiency. Urinary incontinence is defined as involuntary discharge of urine associated with psychologic and hygienic problems. Of 3,248 women investigated between 1986 and 1990 at our Clinic for Climacteric Dysfunctions, Vienna, 1,039 women (32%) reported symptoms such as vaginal dryness, incontinence and problems with regard to cohabitation. Indications for estrogen replacement therapy in and/or after the climacteric period are urinary stress incontinence degree I, urge incontinence (pollakisuria, nycturia), atrophic urethritis as well as preoperative estrogen replacement. For therapeutic management both conjugated estrogens and estradiol as well as estriol preparations may be employed, taking the contraindications into account. Postmenopausal estrogen replacement is highly indicated with dysfunctions in the area of urethra and urinary bladder. PMID- 1615680 TI - [A main symptom of the climacteric manifestation complex: arthropathia climacteria]. AB - In the last few years several studies have been published raising the question whether hormonal factors are co-responsible for the female prevalence of certain joint diseases. From our own clinical experience we know that more than half of the women seen at our outpatients department because of disorders of the post menopausal syndrome complain about arthralgies (especially of the PIP-joints). We have introduced the term "arthropathia climacterica" for it. Moreover the positive results of two clinical studies on which effects hormone replacement therapy had on these complaints indicate a relation between estrogens and joints. PMID- 1615681 TI - [Differentiated therapy of the climacteric syndrome]. AB - The replacement therapy is postmenopausal women is seen to be for transformation of the oestrogen-stimulated endometrium only, which does not apply to hysterectomised women. Because of the influence of estrane on lipids, one often advises against a replacement therapy with progestogens in hysterectomised women. With increasing knowledge of encountered extragenital functions of sexual steroids, the latter is questionable, if natural progesterone is given, which is (said to be) lipid-neutral, performing the function of the progestogens, which is quite more than reproduction only, more efficiently than estrane or gonane. Due to the competitive blocking of aldosterone the effect of progesterone is sodium diuretic and diuretic, being as important as the therapy of climacteric complaints, as well as the consequence, which is the result of the physiological connection between progesterone and encephalics. Moreover, the effect of the progestogens is to tonicise the vascular system and is linked to a number of intestinal hormones in order to adjust their function. Therefore, progesterone seems to perform a great variety of extragenital functions. Menopausal women should not be deprived of the benefits of these functions within the framework of a replacement therapy. PMID- 1615682 TI - [The osteoprotective effect of ovarian hormones]. AB - Osteoporosis is regarded as a disease of the systems controlling bone evolution. Estrogen modulates such a control system; without estrogen 50% of bone is not formed to the peak bone mass or may be lost lateron. Substitution with estrogen can be interpreted as a natural right of the women in our society. Estrogen modulates by dynamic hormonal system the genexpression in bone and determines its three-dimensional architecture. Substitution with estrogen has to consider the individual genetic situation of each women and its biographic and health situation. Individual estrogen substitution is not fully realized yet but estrogen substitution prevents osteoporosis effectively. We question if senile osteoporosis exists at all if there were no estrogen deficiency. PMID- 1615683 TI - [Bone density screening in females in climacteric]. AB - Bonestability is not only determined by the content but also by the construction of the mineral part and the biochemical structure. In addition the organic parts are important, too. Result of the measurements shows only the bone-quantity. The development of several measurement techniques (highquality quantitative computertomography [QCT]) allow us diagnoses concerning the bone quality. Single photon absorptionsdensitometry (SPA), DPA (dual photon absorptiometry), DEXA (dual energy X-ray absorptiometry) and QCT (quantitative computertomography, peripher and central) are todays measurement techniques. In the meantime SPA looses the importance, also DPA-method is displaced by DEXA. PMID- 1615684 TI - [Hormone substitution in climacteric and postmenopause. Consensus report of the Austrian Menopause Society]. PMID- 1615685 TI - [Menopausal bone density in healthy females of Voralberg. Lack of relation to anamnesis]. AB - Bone density was evaluated in 182 healthy climacteric women. Women were recruted from a general prevention program. The results show deviation from 58.2 to 218.6- mean value 128.28, SD 30.91 mg/ccm K2HPO4. 28% of bone density values are under the fracture risk level citated in literature. No statistical relationship was found between bone density and anamnestic data--only the age at hysterectomy shows statistical correlation. The follow up after one year shows no predictive value of anamnestic data to the lost of bone mineral density. PMID- 1615686 TI - Introduction: research directed to improving women's occupational health. AB - This paper reviews briefly recent developments in research on women's occupational health and safety in five areas: documenting the unexpectedly heavy physical and mental workload involved in occupations traditionally assigned to women; showing the consequences for women's health of their precarious relationship to the work force; demonstrating the health effects of the double workday; studying the effects of work on those aspects of biology that are sex specific; suggesting ways to remove ergonomic barriers to women entering non traditional jobs which have been designed in relation to the typical male body. Suggestions are made for future research in these areas, in response to the needs of working women. This paper serves as an introduction to the volume of Women and Health dealing with women's occupational health and safety. PMID- 1615687 TI - Impact of the participation of women in science: on rethinking the place of women especially in occupational health. AB - Recently, women have become scientists in increasing numbers. The present article uses a perspective drawn from the sociology of knowledge to examine the impact of this participation on science, especially the study of occupational health and safety. Five evolutionary stages are described: (1) Inclusion of women as scientific workers; (2) Inclusion of women as subjects of scientific research; (3) Inclusion of variables relevant to women, rather than merely applying to women the factors used to explain men's situations; (4) Using new methodologies to reveal the complexity and the specificity of women's life situations, in addition to those tools developed while studying male populations; (5) Questioning the values on which traditional science has been based, and orienting research according to feminist values. Examples from the study of women's occupational health illustrate these five stages. It is suggested that scientific research oriented toward the well-being of women workers will not only yield a better understanding of women's conditions but also lead to a rethinking of standard practices for research on men's conditions. PMID- 1615688 TI - Heat exposure standards and women's work: equitable or debatable? AB - Although there is an abundant literature on the health effects of occupational heat exposure, very few authors have addressed the question of the effects of heat stress on women workers. Knowledge about the effects of work in hot environments is mainly derived from the study of "heavy" muscular activity and current heat exposure standards are based on an energy criterion according to metabolic load. Metabolic load does not reflect cardiac strain associated with sedentary, repetitive work, involving static effort. The research presented here was conducted in an industrial laundry with 11 women mangle operators exposed to moderate heat stress during the summer months and whose work activity is classified as light on the basis of energy expenditure. Physiological and symptomatological responses, work activity and ambient temperature were assessed over 3 complete work days in summer and in winter. Recorded and perceived temperature, discomfort, feelings of fatigue and symptoms of thermal stress were significantly higher in summer than in winter. Symptoms of drowsiness and musculo skeletal aches were reported equally in both seasons. Heart rate was high in both seasons, as were calculated indices of cardiac strain. Recommended limits for cardiac strain were surpassed significantly more often in summer than in winter. It is suggested that threshold levels should be redefined to include the prevention of cardiac strain resulting from cumulative effects of heat stress and sedentary, repetitive activity, typical of many women's job with low energy requirement. PMID- 1615690 TI - Health problems of women employed in jobs involving psychological and ergonomic stressors: the case of garment workers in Quebec. AB - Health problems of women whose jobs involved intense time pressure were evaluated in a study of 800 sewing-machine operators employed in Quebec between 1976 and 1985. Information on workers' occupational characteristics were obtained from public records. Symptoms of anxiety and depression, use of medication and disability status were determined by interview. Garment workers had an increased prevalence of slight, moderate and severe disability and higher levels of symptoms of anxiety and depression when compared to workers in other occupations. Garment workers paid piecework rates took medication for stomach problems in greater proportion than workers paid an hourly wage. Furthermore, workers who spend 5-9, 10-14, 15-19 and 20 or more years in piecework had an increased prevalence of severe disability compared to the baseline category 0-4 years, with adjusted risk ratios of 2.2 (95% CI = 1.14-4.6), 3.3 (95% CI = 1.5-6.9), 3.6 (95% CI = 1.5-8.4 and 2.3 (95% CI = 0.8-6.6) respectively, independent of age, smoking habits, education, type of task and total length of employment. These findings suggest that short-term, non-disabling conditions associated with time pressure by previous authors may have more important long-term sequelae then had been previously documented. PMID- 1615689 TI - Stability of psychological impairment: two year follow-up of former microelectronics workers' affective and personality disturbance. AB - For the past twenty years women's complaints in the microelectronics industry have often been diagnosed as mass psychogenic illness, despite evidence of potential exposure to organic solvents, which have been associated with affect and mood changes. In the present study, the standard version of the Minnesota Multiphasic Personality Inventory (MMPI) was used to evaluate affective and personality disturbance among 63 former microelectronics workers (56 women and 7 men) over a two-year period of time. In both 1986 and 1988, the former workers obtained mean scale score elevations beyond two standard deviations above the normative sample (T = greater than 70) on the MMPI clinical scales of schizophrenia, hypochondriasis, psychasthenia, depression and hysteria. For most scales, 86-88 mean score differences did not attain the 0.05 significance level (two-tailed paired t-test) and no significant differences were observed for 86-88 comparison scale scores = greater than 70 (McNemar paired statistic). Although there were too few men to perform gender comparisons, men scored higher than women on 5 scales and all of the men had scores = greater than 70 on hypochondriasis, depression, hysteria, psychasthenia and schizophrenia. These findings reveal that these former microelectronics workers manifested affective and personality disturbances, consistent with organic solvent toxicity, which persisted over a two year period, indicating that they were not reactive, transient hysterical neurosis. PMID- 1615691 TI - Ergonomic analysis of work activity of data entry clerks in the computerized service sector can reveal unrecognized skills. AB - Women are highly represented in those computer service jobs which are supposed to require the lowest level of qualification. The complexity of the activities which contribute to accomplishing such tasks in real life is usually unrecognized, as are the skills needed to perform these activities. The requirements of one such job, held by 7 women in a university administration, have been documented by ergonomic analysis. According to the supervisors, little mental effort was required, and "the employees do the job without even thinking about it." However, study of the real tasks involved revealed that the job required a great deal of innovative thinking, all of it unrecognized by the employer, and some of it actually forbidden. However, because the knowledge was not arrived at through systematic training, it is fragmentary and does not permit the employee to be fully autonomous or to transfer her skills to other jobs. PMID- 1615692 TI - How pregnant workers see their work, its risks and the right to precautionary leave in Quebec. AB - In 1981, the Quebec government passed a law providing "precautionary leave" or reassignment to other jobs for pregnant workers exposed to a risk for their health or that of their fetus. This measure was much more popular than expected, with about 30% of pregnant workers taking leave in 1987. Uncertainty about what constitutes a risk for pregnancy, conflicts between views of pregnancy as a social or private act, and differing ideas on employers' responsibility for protection of pregnant workers have combined with worries about cost to stimulate debate on this law. Since 1986, there has been pressure on the government to restrict access to precautionary leave. This article describes research designed to answer some of the questions raised during the debate. Data banks of the Health and Safety Commission and responses of 2500 women workers were examined to characterize the jobs of women who did and those who did not take leave. Leave was usually taken by those who worked in sectors traditionally associated with risks, and women who applied for precautionary leave more often reported their working conditions to be difficult. Women taking leave accorded more importance to their maternal and domestic roles, but equal value to their roles in the workplace. The article concludes that the popularity of the measure is not due to laziness or lack of responsibility on the part of women workers, but to poor conditions in women's traditional jobs. It is suggested that more emphasis be placed on improving conditions rather than on early leave from work. PMID- 1615693 TI - Integration of women into traditionally masculine jobs. AB - Jobs are often allocated according to sex, although this distribution is not always justified by biological differences between men and women. Ergonomic analysis of sex-typed jobs in a clothing factory and in a plastics factory revealed that the total weight lifted in women's jobs exceeded that in a typical male laborer's job. The characteristics of work organization and work rhythm also differed according to the sex to whom jobs were assigned: Muscular exertion was intense but sporadic with the men's jobs, moderate but continuous with the women's. Scientific study has not related characteristics of sex-typed jobs to differences between the sexes in average size and shape. However, analysis of two cases showed that average-sized women entering traditional men's jobs may be disadvantaged, if no thought is given to adjusting tools, equipment and work stations. Trying to do a job designed for larger, heavier people may cause health and safety problems. Any improvement in the conditions of these jobs to take into account a wider range of physical characteristics will benefit men as well as women. PMID- 1615694 TI - The status of the health care financing crisis in Wisconsin 'medicina nusquam non est' (medicine is universal): X. PMID- 1615695 TI - WIPRO and the justification of existence. PMID- 1615696 TI - A moral response to the problems of the medical care system. PMID- 1615697 TI - Patient satisfaction with breast reconstruction. AB - Thirty-two women were surveyed to assess their satisfaction with breast reconstruction after mastectomy for cancer. Most reconstructions consisted of a submuscular implant, and were performed after an average interval of 11.3 months. The procedures averaged 2.4 per individual, and nearly half of the women reported requiring an operation on the opposite breast to attain symmetry. Despite the fact that 60% of the reconstructions resulted in a complication or complaint, women reported that they felt more balanced and whole and less depressed, and all were glad that they had breast reconstruction. PMID- 1615698 TI - Acute confusional migraine: case series and review of literature. AB - Acute confusional state (ACS) as a manifestation of migraine in the pediatric age group was initially described by Gascon and Barlow. The characteristics and natural history of acute confusional migraine (ACM) have been elaborated on by other authors. The diagnosis of ACM is, however, easily overlooked in clinical practice, due to its peculiar presentation. We describe three children who had acute onset of confusion. The differential diagnosis of acute confusional state and the clinical features and management of ACM are discussed. PMID- 1615699 TI - A rationale for universal screening for childhood lead poisoning. PMID- 1615700 TI - Reductive metabolism of the anticonvulsant agent zonisamide, a 1,2-benzisoxazole derivative. AB - 1. The metabolism of zonisamide in vitro was characterized through aerobic and anaerobic incubations with rat liver subcellular fractions and cultured gastrointestinal microflora. 2. Zonisamide reacted with rat hepatic microsomal cytochrome P-450 and exhibited a Type I binding spectrum. 3. Metabolism of zonisamide in vitro by hepatic subcellular fractions and cultured gastrointestinal flora produced a single metabolite, 2-(sulphamoylacetyl)-phenol (2-SMAP), by reductive cleavage of the 1,2-benzisoxazole ring. 4. The reductive metabolism of zonisamide was primarily mediated by microsomal cytochrome P-450. The soluble fraction enhanced reduction when combined with the microsomal fraction but itself possessed only weak reductive activity. 5. Reduction of zonisamide by the most enzymically active liver fractions required NADPH, was stimulated by FMN and SKF-525A, and was inhibited by CO or air, as well as by n octylamine. 6. Unlike their involvement in the reduction of numerous nitro, azo, and N-oxide compounds, cultured aerobic and anaerobic intestinal flora were not principally involved in the reduction of zonisamide. PMID- 1615701 TI - Propofol metabolism in man during the anhepatic and reperfusion phases of liver transplantation. AB - 1. An i.v. dose of 14C-propofol (0.53 mg/kg) was administered to three male and three female patients during the anhepatic phase of liver transplantation, which lasted 30-56 min after dosing. Arterial and venous blood samples, bile (T-tube drainage) and urine were collected at various times afterwards and submitted to h.p.l.c. and radioassay or specific fluorescence detection for the unchanged drug. 2. Extrahepatic metabolism was apparent during the anhepatic phase, since at 30 min post-dose, unchanged propofol comprised only 42-89% of the blood radioactivity. 3. Examination of the plasma radioactivity during the anhepatic phase in two subjects showed evidence of propofol glucuronide and 4-quinol sulphate, confirming extrahepatic metabolism of the drug. Quinol glucuronides were only detected in the liver reperfusion phase. 4. There was no evidence that the lungs contribute to the extrahepatic metabolism of propofol, since drug concentrations in the arterial blood were not less than in central venous samples. 5. During the first 24 h period, urine collected from five patients contained 7-74% dose, whilst the bile contained 0.1-0.9%. In three patients with normal renal function recovery in urine was 66-74% dose. Examination of urinary radioactivity in one subject showed the main component to be propofol glucuronide during the anhepatic phase. PMID- 1615702 TI - Effects of methimazole on the kinetics of netobimin metabolites in cattle. AB - 1. The effects of methimazole (MTZ) on the pharmacokinetic behaviour of netobimin (NTB) and its albendazole (ABZ) metabolites were studied in calves. NTB trisamine salt solution was given by subcutaneous (12.5 mg/kg) and oral (20 mg/kg) routes, either alone or co-administered with MTZ (1.5 mg/kg, intramuscularly). 2. NTB parent drug was detected only after s.c. treatments, showing rapid absorption, early Cmax and fast disposition. ABZ was not found in plasma at any time after either s.c. or oral treatments. 3. Concomitant treatment with MTZ significantly increased the albendazole sulphoxide (ABZSO) elimination half-life (t1/2 beta) (321%) and mean residence time (MRT) (170%) from the values obtained after s.c. treatment with NTB alone. 4. Oral treatment resulted in an ABZSO pharmacokinetic profile with an AUC 27% higher, a significantly longer t1/2 beta (151%) and MRT (124%) in the presence of MTZ. 5. We conclude that when co-administered with NTB in cattle, MTZ induces significant changes in the disposition kinetics of the anthelmintically active ABZSO metabolite. PMID- 1615703 TI - Biotransformation of the hexachlorobutadiene metabolites 1-(glutathion-S-yl) pentachlorobutadiene and 1-(cystein-S-yl)-pentachlorobutadiene in the isolated perfused rat liver. AB - 1. The first step in the bioactivation of the nephrotoxin hexachlorobutadiene is the biosynthesis of 1-(glutathion-S-yl)-1,2,3,4,4-pentachloro-1,3-butadiene (GPCB). GPCB formed in the liver is secreted into bile, may be reabsorbed in the gut, intact or after hydrolysis to 1-(cystein-S-yl)-1,2,3,4,4-pentachloro-1,3 butadiene (CPCB), and undergo enterohepatic circulation or translocation to the kidney. Hepatic uptake and metabolism of GPCB and CPCB may thus influence the disposition of these S-conjugates. We therefore studied the metabolism and uptake of CPCB and GPCB in the isolated perfused rat liver. 2. Dose-dependent uptake of GPCB and CPCB from the perfusion medium by isolated perfused liver was demonstrated; CPCB is cleared from the perfusion medium to a much higher extent than GPCB. 3. GPCB and CPCB are intensively biotransformed to biliary metabolites. These metabolites were identified by thermospray mass spectrometry as products of the conjugation reaction of GPCB and CPCB with glutathione and subsequent hydrolysis of the glutathione moieties. 4. Hepatic biosynthesis of 1 (N-acetyl-L-cystein-S-yl)-1,2,3,4,4-pentachloro- 1,3-butadiene from CPCB was only a very minor pathway in GPCB and CPCB metabolism in liver. 5. The results indicate that hepatic biosynthesis of mercapturic acids may not contribute to the disposition of S-conjugates formed from hexachlorobutadiene in vivo and that GPCB may be, at least in part, delivered intact to the kidney. PMID- 1615704 TI - Inhibition of human and rabbit liver steroid and xenobiotic UDP glucuronosyltransferases by tertiary amine drugs--implications for adverse drug reactions. AB - 1. To investigate the hypothesis that disruption of glucuronidation of endogenous compounds by drugs represents a potential mechanism for pathogenesis of adverse drug reactions, the effects of a range of tertiary amine and amide drugs (many with effects on sex hormone function) on steroid hormone and xenobiotic UDP glucuronosyltransferase activities in human and rabbit liver microsomes were studied in vitro. 2. Chlorpromazine, amitriptyline, imipramine, promethazine and cyproheptadine were consistently the most potent inhibitors of the glucuronidation of testosterone, androsterone, oestriol and 1-naphthol, the steroid activities being more susceptible to inhibition (up to 90%). 3. Carbamazepine, diphenhydramine, sulphadimethoxine, dimenhydrinate and (+/-) chlorpheniramine had little effect on the UDPGT activities measured. 4. The structural features within this group of compounds required for inhibitory potency were the presence of a rigid tricyclic ring (e.g. phenothiazine) and either a dimethylaminopropyl or a methylpiperidine side-chain. 5. The implications of these data for involvement of disruption of the normal cellular function of glucuronidation in the pathogenesis of frequently observed adverse side-effects associated with these compounds are discussed. PMID- 1615705 TI - The effects of cobalt chloride, SKF-525A, and N-(3,5-dichlorophenyl)succinimide on in vivo hepatic mixed function oxidase activity as determined by single-sample plasma clearances. AB - 1. Four drugs--antipyrine, theophylline, quinidine, and ethosuximide--were used as probes of in vivo hepatic mixed function oxidase (MFO) activity. Functional MFO activity was evaluated by estimating probe clearances subsequent to pretreatment of rats with either cobalt chloride, SKF-525A, or N-(3,5 dichlorophenyl) succiminide (NDPS). 2. Clearances of each probe were estimated from single plasma concentration measurements. Each pretreatment altered the clearances of this panel of probes in a different way. NDPS pretreatment increased theophylline clearance while slowing quinidine and ethosuximide clearances. SKF-525A slowed all probe clearances except for ethosuximide. Cobalt chloride slowed all probe clearances except for theophylline. 3. The use of multiple probes as substrates for the hepatic cytochrome P-450 system can provide some insight into the functional consequences of xenobiotic exposures on that system. Moreover, xenobiotic-induced functional changes on hepatic MFO when assessed in vivo appear to be modest relative to changes in in vitro activity or hepatic cytochrome P-450 content. This minimally invasive multiprobe method may be useful for assessing xenobiotic influences on human hepatic MFO in vivo. PMID- 1615706 TI - Metabolism of (-)-6(S)-hydroxy-4(R)-(1-hydroxy-1-methylethyl)-1- cyclohexene-1 ethanol in rat and dog. AB - 1. The metabolism of a new mucoactive drug, chemically (-)-6(S)-hydroxy-4(R)- (1 hydroxy-1-methylethyl)-1-cyclohexene-1-ethanol (CO/1408), has been studied in rat and dog after a single oral dose; eight metabolites were identified. 2. Oxidation of the primary and secondary alcohol groups, hydroxylation in allylic positions and conjugation with glucuronic acid occurred in both species. Products of oxidation on the double bond have not been identified. 3. Using reversed-phase h.p.l.c. and beta-cyclodextrin in the eluent it was found that the glucuronide metabolites varied with species and with the biological fluid examined. PMID- 1615707 TI - Effects of hypophysectomy and testosterone treatment on the urinary excretion of zenarestat in rats. AB - 1. The effects of hypophysectomy and androgen treatment on the urinary excretion of zenarestat were investigated in Sprague-Dawley rats. 2. Hypophysectomized male rats and normal female rats has similar urinary excretion of zenarestat which was much greater than that of normal male rats. 3. Treatment of male and female hypophysectomized rats with testosterone resulted in the urinary excretion of zenarestat characteristic of intact adult male rats. 4. Urinary secretion of zenarestat in rats is independent of pituitary hormone and is suppressed only by androgen. PMID- 1615708 TI - Absorption, distribution and excretion of zenarestat, a new aldose reductase inhibitor, in rats and dogs. AB - 1. The absorption, distribution and excretion of zenarestat have been studied in male rats and dogs after i.v. and oral administration of 14C-zenarestat. 2. The bioavailability of zenarestat was 93% in rats and 65% in dogs. A major proportion of the plasma 14C in rats and dogs was due to unchanged drug. The terminal elimination half-life of zenarestat in plasma was 6 h in rats and dogs. 3. Except for organs associated with absorption and elimination, tissue 14C levels were lower than plasma levels in rats. The distribution to, and elimination from sciatic nerve were slower than those of other tissues. 4. Most of the 14C from 14C-zenarestat administered orally and i.v. to rats and dogs was excreted in the faeces. After i.v. dosing to bile duct-cannulated rats, 96% of the radioactive dose was excreted in the bile. PMID- 1615709 TI - Biological fate of sulphur mustard (1,1'-thio-bis(2-chloroethane)): urinary and faecal excretion of 35S by rat after injection or cutaneous application of 35S labelled sulphur mustard. AB - 1. A technique for the quantitative cutaneous application of sulphur mustard vapour is described. The maximum rate of uptake of the agent vapour by shaved rat skin in vivo was estimated as 7 micrograms/cm2 per min. 2. The major route of excretion was through the kidneys: greater than 70% of the radioactivity of all doses was excreted in 3 days after either i.v. or i.p. injections of 35S-labelled sulphur mustard, but less (50-70% depending on dose) was excreted in the same time following cutaneous application. 3. This urinary excretion of 35S had a half life of 1.4 days, and the decreased proportion of the applied dose excreted following cutaneous application may be accounted for by retention of radioactivity in the skin. 4. The contribution of faecal excretion was greater following cutaneous application. PMID- 1615710 TI - Metabolism of phenol in the terrestrial snail Cepaea nemoralis L. AB - 1. The metabolism of phenol in the terrestrial snail Cepaea nemoralis was studied after injection into the haemocoel of the dorsolateral foot region. 2. Excreted metabolites, and metabolites extracted from the body, were analysed by h.p.l.c. In addition to phenyl beta-D-glucoside, arbutine (quinol beta-D-glucoside), a new conjugate of phenol, was detected. PMID- 1615711 TI - Cytochromes P-450 in rats: structures, functions, properties and relevant human forms. PMID- 1615712 TI - [Sonography in gallbladder diseases]. PMID- 1615713 TI - [Ultrasound diagnosis of the gastrointestinal tract without (native) and with water filling (hydrosonography)]. PMID- 1615714 TI - [Endoscopic retrograde cholangiopancreatography (ERCP). An assessment of its status]. PMID- 1615715 TI - [Extracorporeal shockwave lithotripsy (ESWL) of gallbladder calculi in combination with oral litholysis. Results of the first 180 patients of the Charite Internal Medicine University Clinic]. PMID- 1615716 TI - [Bacterial colonization of gallstones]. PMID- 1615717 TI - [Hepatic encephalopathy: long-term therapy with neomycin is problematic]. PMID- 1615718 TI - [Adrenergic beta blockade in liver cirrhosis with portal hypertension? Doppler ultrasound measurement of the short-term effect of propranolol on the portal system]. PMID- 1615719 TI - [Follow-up of chronic hepatitis B in patients with kidney transplantation: comparison between kidney transplant patients and hemodialysis patients]. PMID- 1615720 TI - [Selected aspects of therapy of systemic lupus erythematosus]. PMID- 1615721 TI - [Antihypertensive combination therapy with ACE inhibitors]. PMID- 1615722 TI - [Diagnostic bronchoalveolar lavage]. PMID- 1615723 TI - [Screening for bronchial cancer. A case-control study]. PMID- 1615725 TI - [Secondary malignant neoplasms following postoperative radiotherapy of breast cancer]. PMID- 1615724 TI - [Prognostic factors in lymph node negative breast cancer patients]. PMID- 1615726 TI - [Surgery of intestinal arteries. 1: Acute intestinal ischemia syndrome]. PMID- 1615727 TI - [Sudden cardiac death: can individual risk be predicted?]. AB - Only 30-40% of all victims of sudden cardiac death could so far be classified as risk patients during their lifetime. Risk factors for sudden death have little predictive value in an asymptomatic population: for example, the typical risk profile for the presence of coronary heart disease and changes in the surface-ECG at rest and especially in the surface-ECG under stress. Usually, the victims of sudden cardiac death among top performance athletes have been suffering from a heart disease of which they knew nothing beforehand: below 40 years of age, mostly from hypertrophic cardiomyopathy; beyond 40, predominantly from coronary heart disease. Among the heart diseases, sudden cardiac death is the cause of death most often in hypertrophic cardiomyopathy, in dilatative cardiomyopathy and in certain types of coronary heart disease. Notwithstanding the employment of fully update cardiological diagnostics the risk patients cannot be identified with reliable precision among those suffering from these diseases. It is only clinically manifest persistent ventricular tachycardia or successful reanimation in case of ventricular fibrillation that will definitely pinpoint the patient as being at risk of sudden cardiac death also in the future. PMID- 1615728 TI - [Anti-arrhythmic drug prevention of sudden cardiac death--the status after the CAST study]. AB - Sudden cardiac death is caused by ventricular tachyarrhythmias. Therefore, antiarrhythmic drugs have been widely used in the prophylaxis of this lethal event. However, all studies using "classical" antiarrhythmic drugs (class 1) for this purpose have shown an enhanced mortality in the patients treated. One of the major causes for these disappointing results are probably proarrhythmic effects, which are especially observed in patients with reduced left ventricular function. Obviously a normal Holter ECG during the titration phase cannot exclude proarrhythmic events during long-term follow-up. In addition, the suppression of ventricular premature beats by an antiarrhythmic agent seems not to be an useful criterium as far as the prophylaxis of sudden death is concerned. The crucial prerequisit for the induction of the lethal arrhythmia is the "arrhythmogenic substrate" which clinically can only incompletely analysed by recording of late potentials or programmed ventricular stimulation. From the therapeutical point of view we need drugs which can modulate this arrhythmogenic substrate i.e. antifibrillatory acting drugs and not antiarrhythmic drugs in the classical sense. Beta blockers and class 3 drugs are the first step in this direction. PMID- 1615729 TI - [Which patient with sustained ventricular tachycardia is suited for long-term therapy with anti-arrhythmia drugs?]. AB - Therapy of patients with a history of sustained ventricular tachycardia essentially depends on the type and extent of underlying cardiac disease. This survey presents older and newer results regarding the outcome of this arrhythmia in relation to QRS morphology and underlying disease: monomorphic ventricular tachycardia without underlying cardiac disease; monomorphic ventricular tachycardia on the basis of right ventricular dysplasia; monomorphic ventricular tachycardia in coronary artery disease or dilated cardiomyopathy; polymorphic ventricular tachycardia with/without QT prolongation. Apart from complete hemodynamic evaluation of all cases with documented sustained ventricular tachycardia, programmed ventricular stimulation should be performed. Because of the excellent long-term outcome and the regularly benign clinical symptomatology, antiarrhythmic drugs are and will remain the therapy of first choice in patients without underlying cardiac disease. In exercise-induced arrhythmias, beta blocking agents are to be used in the first place. As an exception to the general rule, special forms of ventricular tachycardia without underlying cardiac disease respond to verapamil. The clinical symptomatology during ventricular tachycardia on the basis of coronary artery disease or dilated cardiomyopathy is typically severe with a guarded outcome. Long-term therapy with antiarrhythmic drugs should be performed only when the efficacy was proved by serial electrophysiologic drug testing (suppression of inducibility of the arrhythmia). Regarding drug testing, the class III antiarrhythmic drugs sotalol and amiodarone seem to be more effective than the class I antiarrhythmic drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615730 TI - [Catheter ablation of ventricular tachycardia]. AB - Catheter ablation of ventricular tachycardias was performed in a total of 80 patients whose tachycardias were considered as drug refractory and who were not considered to be candidates for antitachycardic surgery or implantation of an automatic cardioverter defibrillator. After careful endocardial catheter mapping including pacing interventions, either direct-current (DC) (n = 61) or radiofrequency current (RF) (n = 13) or both (n = 6) were applied of the "site of origin" of ventricular tachycardia or the "zone of slow conduction". 42 of 51 patients with coronary heart disease were discharged; ventricular tachycardia recurred in 8 cases, and 2 patients died suddenly. In the remaining 32 patients, there were no recurrences of ventricular tachycardia during a mean follow-up period of 12 month. Three patients died perioperatively. In 21 of 29 patients without coronary artery disease, no recurrences of ventricular tachycardia were observed (mean duration of follow-up 17 months) whereas 8 cases had a recurrence of ventricular tachycardia. PMID- 1615731 TI - [Implantable defibrillators]. AB - Automatic implantable defibrillator therapy has changed the approach to life threatening ventricular tachycardia completely and essentially improved survival after aborted sudden cardiac death. Since the first implantation of a defibrillator in 1980, 20,000 patients have received such a device. Nonetheless, in Germany still too many patients die of sudden cardiac death because defibrillator therapy fails to be known enough and keeps not being made use of (no more than 1,000 implants to date). In this group of patients characterized by poor ventricular function, antiarrhythmic drug therapy proved to be unreliable or even dangerous in many cases, while electrophysiologically-guided surgical interventions use to be impossible. The introduction of the implantable defibrillator enabled the incidence of sudden cardiac death to be reduced to about 2% during the first year after implant, and to 5% in the third year, respectively. In most centers with more extensive experience in defibrillator implantations, operative mortality is about 2-3%. Long-term results with defibrillator patients are controlled by the course of the underlying disease, which is coronary artery disease with large scars due to infarction in some 75% of cases. In a large group of about 10,000 patients, total mortality has been calculated to be 15% after three years. Defibrillator systems of the latest generation offer multiple programmability of tachycardia identification parameters and permit differentiated modification of therapeutic intervention. Defibrillator therapy has now been improved essentially by the introduction of endocardial lead systems and, in addition, by the defibrillator being combined with an antitachycardia pacing system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615732 TI - [Electrophysiologic operations. Surgical treatment of life-threatening tachycardia: indications, surgical possibilities, results]. AB - Electrophysiologic operations, which mean electrophysiologically (= mapping) guided direct operations for life-threatening tachyarrhythmias have been elaborated and popularized during the decade of 1980-1990. They are predominantly related to patients with supraventricular tachycardias on the basis of accessory atrioventricular bypass tracts (Wolff-Parkinson-White syndrome) and individuals with malignant ventricular tachycardias in the setting of coronary artery disease. The concept of these operations is to identify the tachycardia underlying morphologic substrates at time of surgery utilizing intraoperative electrophysiologic mapping techniques and to ablate those arrhythmogenic tissues surgically. In comparison to the natural (= non-surgical) history of the mentioned disorders their mortality and morbidity prognosis is significantly improved through direct antitachycardiac operations. Possibly the spectrum, indications and applications of those electrophysiologic operations will change through the next decade since the meantime a variety of rhythm disorders are successfully approached by interventional cardiologic measures. PMID- 1615733 TI - [Familial primary generalized epilepsy and drug (anticonvulsant)-induced systemic lupus erythematosus--a family study]. AB - We report a 12-year study of a family with high mortality rate due to primary generalized epilepsy. During indicated and non-indicated therapy with anticonvulsive drugs (succinimides and hydantoines) there developed symptoms of systematic lupus erythematosus. The value of controlled immunological and genetic markers is discussed. PMID- 1615734 TI - [Systemic lupus erythematosus and pregnancy]. AB - Our study strengthens the view that successful pregnancy outcome can be achieved in most patients with SLE, although premature delivery and pregnancy-related complications are common. For the differential diagnosis of preeclampsia and lupus flare in pregnancy, levels of anti-DNA antibodies and complement C3 are valuable parameters. In patients with antibodies to phospholipids, no major clinical problems occurred provided that patients were treated with corticosteroids and low-dose aspirin. However, none of our patients with renal involvement of SLE had an uncomplicated pregnancy course. PMID- 1615736 TI - Arrhythmias in the natural history of mitral stenosis. AB - Mitral stenosis with or without regurgitation is the most common form of valve disease associated with arrhythmias, as atrial fibrillation (AF) is the most frequent complication of mitral stenosis. AF may occur as transient episodes with the patients reporting a history of palpitation, paroxysmal dyspnea or tachycardia or as sustained arrhythmia. PMID- 1615735 TI - [Enzyme immunoassay for the detection of autoantibodies to nRNP and Sm: a rapid and sensitive alternative to current procedures]. AB - Antinuclear antibodies are of major importance in the diagnosis of inflammatory rheumatic diseases. Sm and nRNP antibodies can be found in sera from patients with systemic lupus erythematosus and mixed connective tissue disease. Usually, these antibodies have been detected with one of the following methods: Ouchterlony immunodiffusion, passive hemagglutination or counterimmunoelectrophoresis (CIE). In this work results obtained by Ouchterlony and CIE techniques were compared with those obtained by ELISA. Purified proteins from cellular extracts (HeLa) were used as antigens for Sm- and nRNP-ELISA: D polypeptide for Sm-ELISA and the 68 kD, A, C, B,B' and D polypeptides for nRNP ELISA. Compared with the other two techniques, ELISA was less time consuming and showed greater sensitivity. Quantitative titration proved to be of advantage in monitoring the course of the diseases mentioned above. PMID- 1615737 TI - Features of patients with severe mitral stenosis with respect to atrial rhythm. Atrial fibrillation in predominant and tight mitral stenosis. AB - The aim of this study was to assess the features of patients with severe mitral stenosis in relation to atrial rhythm. Six hundred and fifty patients (pts) with severe mitral stenosis (MS) (valve area less than or equal to 1.5 cm2) who underwent percutaneous balloon commissurotomy (n = 600) or surgery (n = 50) were classified into 3 groups according to their atrial rhythm (AR): group A: sinus rhythm (SR) (n = 379), group B: SR with episodes of transient atrial fibrillation (AF) (n = 65), group C: permanent AF (n = 206). Uni- and multivariate analysis of clinical, echocardiographic and hemodynamic parameters with respect to the atrial rhythm was performed. Some parameters were comparable in all 3 groups: sex, pulmonary, right and left atrial pressures, mitral valve area, incidence of associated aortic valve disease. Nine parameters were different: mean age, NYHA class III or IV, previous commissurotomy, previous embolism, cardiac index, mitral regurgitation, tricuspid regurgitation, left atrium diameter, mitral calcification. Multivariate analysis, identified age, left atrial diameter and presence of mitral calcification as independent predictors of atrial fibrillation. Transoesophageal echocardiography was performed in 167 cases. A spontaneous echo contrast was recorded in 106 cases (63.5%) and was significantly correlated with a history of embolism and or left atrial thrombi detected by echocardiography. Atrial fibrillation, size of left atrium, severity of mitral stenosis and cardiac index were found to be independent predictive factors of spontaneous echo contrast. PMID- 1615738 TI - Ventricular arrhythmias and mitral valve prolapse. PMID- 1615739 TI - Arrhythmias in the natural history of aortic stenosis. AB - In aortic stenosis, severe ventricular arrhythmias may be linked to left ventricular dysfunction and are a factor to be considered when a surgical decision is to be made. Conduction disturbances are frequent, sometimes not related to the severity of the stenosis and may endanger patient's life. PMID- 1615740 TI - Arrhythmias in aortic regurgitation: incidence, consequences and treatment. PMID- 1615741 TI - Ventricular arrhythmias in aortic valve disease before and after aortic valve replacement. AB - In order to evaluate the effect of aortic valve replacement on the incidence of ventricular arrhythmias in patients with aortic valve disease, 24-hour ambulatory electrocardiographic recordings were obtained before surgery in 96 patients without coronary artery disease (aortic stenosis n = 50, combined aortic stenosis and regurgitation n = 19 and aortic regurgitation n = 27). Following aortic valve replacement, repeat recordings were obtained after 13 +/- 4 days and 18 +/- 7 months. Ventricular arrhythmias were in all cases classified according to Lown and were compared with clinical, echocardiographic and hemodynamic data. Preoperatively, ventricular premature beats were observed in 85 patients (89%) and were frequent (greater than 30 ventricular premature beats/hour) in 20 (21%). Multiformity was found in 27 (28%), couplets in 18 (19%) and ventricular tachycardia in 11 (11.5%). The occurrence of ventricular arrhythmias was not related to the type or severity of valve lesions. Patients with severe ventricular arrhythmias (Lown class 3 or 4: 37%) had a greater thickness of their interventricular septum 13.9 +/- 2.5 mm, vs 11.7 +/- 2.6 (p less than 0.05); a higher LV mass 176 +/- 34 g/m2, vs 134 +/- 39 (p less than 0.05) and a lower left ventricular ejection fraction 47 +/- 12%, vs 57 +/- 11, (p less than 0.01). Two weeks postoperatively, the incidence and severity of ventricular arrhythmias had increased: ventricular premature beats were noted in 92% and were severe in 50%. No correlation was found between ventricular arrhythmias and preoperative or operative data. Eighteen months after surgery, ventricular premature beats were still observed in 81% of patients but remained frequent in 7% only. Severe ventricular arrhythmias were noted in 27%. Patients with severe ventricular arrhythmias had at the time of this late recording a lower radionuclide left ventricular ejection fraction 57 +/- 14%, vs 73 +/- 9 (p less than 0.02) and a higher enddiastolic diameter 63 +/- 15 mm, vs 48 +/- 7, (p less than 0.01). This study indicates that ventricular arrhythmias are common in patients with aortic valve disease. The severity of arrhythmias is influenced by the LV consequences of valve lesion both pre- and late postoperatively. The frequency and severity of ventricular arrhythmias increase early after surgery and do not correlate with preoperative or operative data. PMID- 1615742 TI - Permanent cardiac pacing for prolonged second and third degree atrioventricular block complicating cardiac valve replacement. PMID- 1615743 TI - Preoperative ventricular arrhythmias in mitral regurgitation. French Working Group on Valvular Heart Disease. PMID- 1615744 TI - Perioperative arrhythmias in valvular heart disease. PMID- 1615745 TI - Arrhythmias and valvular heart diseases. European Society of Cardiology Working Group on Valvular Heart Diseases. Namur, Belgium, 24-25 May 1991. Proceedings. PMID- 1615746 TI - Possible mechanisms of arrhythmias in valvular heart disease. PMID- 1615747 TI - [Prognosis in chronic myeloid leukemia]. AB - The clinical course of patients with chronic myelogenous leukaemia (CML) is very heterogenous. Survival is determined by the timing of disease transformation. A patient's risk of transformation can be defined, but the time when it will occur can not be predicted. A number of features recorded at the time of diagnosis correlate significantly with survival and can serve as prognostic parameters. Conventional therapy has not achieved a substantial delay in the universally fatal outcome of the disease. Allogenic or syngenic bone marrow transplantation to individuals with CML is at present the only treatment with a curative potential. PMID- 1615748 TI - [Immunologic phenotype of lymphocytes in chronic B-cell lymphocytic leukemia. I. B- and T-lymphocytes in chronic lymphocytic leukemia]. AB - This article contains the review and the critical discussion of studies of T and B lymphocytes in chronic B-cell lymphocytic leukaemia. It is not explicitly known now, which stage of differentiation of lympho-haemopoietic cells undergoes malignant transformation in CLL-B. Basing on VDJ recombination activity it is supposed that some cases derive from the stem cell, others--from B lineage cells. PMID- 1615749 TI - [Immunologic phenotype of lymphocytes in chronic B-cell lymphocytic leukemia. II. Studies of immunologic phenotype of peripheral blood and lymph node lymphocytes in patients with chronic lymphocytic leukemia or leukemic forms of lymphoplasmacytoid lymphoma]. AB - In a group of 16 patients with chronic lymphocytic leukaemia and leukaemic forms of the lymphoma lymphoplasmocytoides immunophenotypes of peripheral blood and lymph node lymphocytes were studied. CONCLUSIONS: 1) immunophenotype heterogeneity observed in a minority of patients in lymph-nodes or peripheral blood seems to be connected with the co-existence of leukaemic and normal reactive B-cells, 2) SIgG+ cells seem to represent activated B lymphocytes producing and secreting autoantibodies, 3) circulating peripheral T lymphocytes do not reflect the distribution of T cell subpopulations in lymph-nodes. PMID- 1615751 TI - [Results of serological tests for syphilis used in preventive examinations]. AB - Results of serological tests for syphilis performed on donors and patients at the Institute of Haematology over the last two years are summarized. The results of tests performed by cardiolipins ++ USR and VDRL antigens, and later confirmed using FTA-ABS and TPHA methods were evaluated. They indicate that the recently produced USR antigen is more sensitive and more specific than VDRL antigen. Similarly, TPHA proves to be more sensitive than FTA-ABS test in these prophylactic assays. PMID- 1615750 TI - [Second cessation of therapy in children with acute lymphoblastic leukemia]. AB - In the group of 63 children in whom a relapse of ALL after first suspension of treatment occurred, and in whom a repeated cessation of therapy had place, 46.2% of patients had probability of a prolonged symptomless survival. The children with an isolated extramedullary relapse had a greater chance for a DFS of 7 years, than those with a relapse in the bone marrow (p = 0.05). The patients with a relapse occurring after the first cessation of treatment of ALL should be treated as intensively as newly diagnosed cases, because they have a real possibility for a prolonged survival during remission phase of disease. PMID- 1615752 TI - [Indications for bone marrow transplantation in failure of the hematopoietic system]. PMID- 1615753 TI - Antileukemic effects of recombinant human tumor necrosis factor alpha (rh-TNF alpha) with cyclophosphamide or methotrexate on leukemia L1210 and leukemia P388 in mice. AB - We investigated the influence of recombinant human tumor necrosis factor alpha (rh-TNF alpha) administered as a single agent or in combination with cyclophosphamide (CY) or methotrexate (MTX) on the survival time of mice inoculated with lymphoblastic leukemia L1210 or lymphatic leukemia P388. The median survival time of leukemia L1210 bearing mice treated with rh-TNF alpha at doses ranging from 200 to 275 g/kg in daily i.p. injections was longer than that of control animals. Groups of mice with leukemia L1210 receiving rh-TNF alpha combined with either MTX or CY lived longer than animals treated with these agents individually. We observed only slight prolongation of life of animals inoculated with this tumor and treated with rh-TNF alpha at dose of 800 micrograms/kg in four injections on 2, 4, 6 and 8 day of experiment, and no effect when rh-TNF alpha was administered at dose of 200 or 400 micrograms/kg at the same treatment regime. In contrast no significant differences in lifetime were obtained from either simultaneous or sequential treatment of mice bearing leukemia P388. Groups of mice with this tumor treated with rh-TNF alpha in conjunction with either MTX or CY lived longer than controls, or rh-TNF alpha singly treated mice, but their survivals were not significantly prolonged compared with mice receiving cytostatics alone. PMID- 1615754 TI - Haemolytic crises caused by Hoya carnosa in a patient with G6PD deficiency. AB - Haemolytic crises caused by contact with Hoya carnosa were observed in a 45-years old woman. The investigation of erythrocyte enzymes displayed both G6PD deficiency and its diminished affinity to G-6-P. Some properties of dehydrogenases isolated from erythrocytes of the patient's brother and son were also changed although clinical signs of haemolysis were absent. PMID- 1615755 TI - Interleukin-6: an osteotropic factor? PMID- 1615756 TI - Intermittent administration of bovine PTH-(1-34) increases serum 1,25 dihydroxyvitamin D concentrations and spinal bone density in senile (23 month) rats. AB - We examined the effect of intermittent administration of bovine parathyroid hormone (1-34) (bPTH) on spinal bone mineral content (BMC) and bone mineral density (BMD), serum 1,25-dihydroxyvitamin D concentrations, and serum markers of osteoblast function in senile male and female rats (23 and 24 months of age, respectively). Sexually mature young (3 month) male rats were similarly treated for comparison. bPTH administration increased serum osteocalcin concentrations without changing serum inorganic phosphate or calcium concentrations in either group of old animals. In young animals, PTH administration increased the serum calcium and inorganic phosphate concentrations significantly (p less than 0.05), although values remained within the normal range. In the vehicle-treated male rats, serum 1,25-dihydroxyvitamin D concentrations were lower in the senile than in the young animals (18 +/- 5 versus 47 +/- 6 pg/ml, p less than 0.05). PTH administration resulted in significantly increased serum 1,25-dihydroxyvitamin D concentrations in the senile and young male animals (both, p less than 0.05) and the final mean serum 1,25-dihydroxyvitamin D concentrations were not statistically different (68 +/- 9 versus 85 +/- 6 pg/ml respectively; p = NS). Serum 1,25-dihydroxyvitamin D concentrations were significantly (p less than 0.05) higher in the PTH-treated senile female rats than the sex-matched, vehicle treated controls. The pretreatment spinal BMC and BMD as assessed by dual-energy x-ray absorptiometry (DEXA) were significantly higher in the senile male animals than in the young animals. Spinal BMC and BMD decreased in the vehicle-treated senile male rats (p less than 0.05) over the 3 weeks of the study despite a gain in weight.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615757 TI - Evidence for P2-purinoceptors on human osteoblast-like cells. AB - ATP released from damaged cells or by controlled secretion could be an important factor in the formation or remodeling of bone. In a variety of other tissues ATP has been shown to control cellular processes by acting on P2-purinoceptors and activating the calcium signaling pathway. Here we demonstrate for the first time that extracellular ATP increases the intracellular free calcium [Ca2+]i concentration in normal human osteoblasts and in SaOS-2 cells, a human osteosarcoma-derived cell line, but not in ROS 17/2.8 cells. The ATP-induced increase in [Ca2+]i was dose dependent, and the concentrations of ATP required were similar to those reported to regulate cellular functions in other cell types. Although ATP is metabolized rapidly by bone cells, the effects on [Ca2+]i appeared to be mediated directly by ATP rather than one of its metabolites. Adenosine 3-thiotriphosphate, a nonhydrolyzable analog of ATP, induced similar changes in [Ca2+]i. This indicates that P2-purinoceptors are present on osteoblast-like cells and that extracellular ATP from various sources might be an important factor in the regulation of osteoblast functions. PMID- 1615758 TI - Developmental regulation of creatine kinase activity in cells of the epiphyseal growth cartilage. AB - During the process of endochondral bone formation, the maturing chondrocyte exhibits profound changes in energy metabolism. To explore the mechanism of energy conservation in cartilage we examined the expression of creatine kinase, an enzyme that catalyzes the formation of ATP in tissues under oxygen stress. Measurement of creatine kinase activity and cytochemical assessment of enzyme distribution clearly showed that the level of enzyme activity was related to chondrocyte maturation. Thus, as the cells hypertrophied, there was a progressive increase in creatine kinase activity. Similarly, an elevation in creatine kinase activity was noted in chondrocyte cultures as the cells assumed an hypertrophic state. When cartilage calcification was disturbed by rickets, there was a decrease in enzyme activity in the hypertrophic region. Studies were performed to examine the creatine kinase isozyme profile of cells of the epiphysis. In resting and proliferating cartilage, the isoform was MM. In hypertrophic cartilage, the predominant isoforms were MB and BB. In terms of the creatine phosphate content, the highest values were seen in the proliferative region; lower amounts were present in hypertrophic and resting cartilage; and no creatine phosphate was detected in calcified cartilage. These data suggest that turnover of creatine phosphate is greatest in the mineralized region of the epiphysis. The results of these investigations point to creatine kinase as being under developmental control. The activity of the enzyme in cartilage cells should serve as a marker of developmental events associated with chondrocyte proliferation, hypertrophy, and mineralization. PMID- 1615760 TI - Retention of etidronate in human, dog, and rat. AB - The retention of radioactivity in human, rat, and dog following a single injected dose of radiolabeled etidronate disodium (EHDP) is shown to follow power-law decay curves with similar slopes for times up to 4, 60, and 80 days, respectively. During this period retention declines with time according to a weak inverse power of the time since dosing, with an exponent ranging from -0.05 (dog) to -0.09 (human and rat). Direct analyses of dog bones either 90 days after a single dose or 365 days after cessation of chronic dosing indicate a more rapid bone clearance of EHDP than predicted by the initial power law. Direct skeletal analysis also shows a more rapid loss of radioactivity in the rat between 60 and 365 days, indicative of either a second power law or a terminal exponential phase in the retention function occurring after 60 days. These data are used to estimate the minimum and maximum amounts of drug that would remain in the body following long-term treatment in humans. For the intermittent cyclic EHDP treatment (ICT) regimen for osteoporosis (repeated cycles of 14 daily doses of 400 mg orally followed by 76 days drug free), the projected retention of EHDP after 3 years of treatment is 25-50 times the daily absorbed dose. Thus, for a 60 kg woman with a daily absorbed dose of 12 mg, the retained mass of EHDP would be about 300-600 mg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615759 TI - Identification of proteins secreted by human osteoblastic cells in culture. AB - To better understand the biochemistry of matrix-forming cells, we developed a simple and reproducible procedure for the isolation and identification by N terminal sequencing of proteins secreted by cells into culture medium and applied this procedure to the analysis of the major Coomassie blue-staining proteins under 100 kD that are secreted from three different human osteoblastic cell cultures. The major proteins secreted by normal human osteoblasts from adult trabecular bone were identified by N-terminal sequencing to be gelatinase, osteonectin, the C-terminal propeptides of the alpha 1 and alpha 2 chains of type I collagen, tissue inhibitor of metalloproteinase 1 (TIMP-1), and beta 2 microglobulin. The amounts of each of these proteins secreted into medium over a 24 h interval did not change over the 7 consecutive days of culture under serum free conditions, which indicates that this pattern of protein secretion is not significantly affected by the serum-free conditions needed for protein identification by this method. In addition, radioimmunoassay for bone gla protein (BGP), a marker for osteoblast phenotype, revealed that BGP secretion remained high over 7 days of culture under serum-free conditions and was comparable to the rate of BGP secretion in control cultures with 10% serum. The major proteins secreted by MG-63 cells were identified by N-terminal sequencing to be gelatinase, a novel 40 kD human bone protein we termed YKL-40, TIMP-1, the recently discovered TIMP-2, and beta 2-microglobulin. Further studies revealed that YKL-40 is the only protein detectable by Coomassie staining of SDS gels of MG-63 media proteins that is induced by extended time at confluence or by treatment with 1,25-(OH)2D3. The apparent absence of detectable Coomassie-stained bands corresponding to the C-terminal propeptides of collagen in the medium of MG 63 cells suggests that these transformed cells may not be a good model for bone matrix formation. The major proteins secreted by normal fetal osteoblastic cells were identified by N-terminal sequencing to be osteonectin and the C-terminal propeptides of the alpha 1 and alpha 2 chains of type I collagen. Gelatinase and TIMP could not be detected among the conditioned medium proteins by these methods. These observations indicate that fetal osteoblasts primarily express proteins that are matrix constituents and adult human osteoblasts secrete, in addition to these, proteins that could function in matrix turnover. PMID- 1615761 TI - Bone mineral density in elderly men and women: results from the Framingham osteoporosis study. AB - Our study investigated bone mineral density of the proximal femur and ultradistal and proximal radius in a population of elderly men and women. The Framingham study started in 1948, following a population-based sample for evaluation of cardiovascular risk factors and events. During the 20th biennial Framingham examination (1988-89) we conducted the Framingham osteoporosis study, measuring bone mineral density in the proximal femur and distal and proximal radius for 1154 study participants. Ages ranged from 68 to 98 years, with a mean age of 76 years. Bone mineral density was measured using Lunar SP2 and DP3 densitometers. This cross-sectional study evaluates mean bone mineral density measurements at each site by 5 year age intervals for men and women, testing for trends in bone density with age. Analyses were repeated adjusting for weight and height. Among the 446 and 708 women, bone mineral density of the femur and bone mineral content of the proximal radius were inversely and significantly related to age in both sexes and were considerably higher in men than women at all sites. The linear decline with age group in our cross-sectional study remained after multivariate adjustment for height and weight. The ultradistal radius showed no significant correlation with age for either sex. There were significant correlations between the bone measurements made at different sites for both men and women (range in r = 0.27-0.89). Cross-sectional curves of bone mineral density with age showed no significant differences in slope between males and females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615762 TI - Prostaglandin E2 promotes osteoclast formation in murine hematopoietic cultures through an action on hematopoietic cells. AB - Osteoclastic differentiation is induced from hematopoietic cells in the presence of 1,25-(OH)2D3 by stromal cells that are present in bone but not in hematopoietic spleen. Recent evidence suggests that prostaglandins (PGs) are essential for this process. In this communication we describe experiments in which we have examined further the role of PGE2 in osteoclast formation. We found a marked reduction in basal, 1,25-(OH)2D3, and IL-3-induced production of calcitonin receptor (CTR)-positive cells and bone resorption by cyclooxygenase inhibitors, which was restored by PGE2 addition. Although some stromal cell types (ST2 cells) that support osteoclast formation from spleen cells produced PGs in response to 1,25-(OH)2D3, others (ts8 and calvarial cells) did not, either alone or in combination with spleen cells. On the other hand, both bone marrow and spleen cells produced amounts of PGE2 in response to 1,25-(OH)2D3 that were sufficient to account for osteoclast formation. Osteoclast-inductive ts8 cells were able to support osteoclast formation from spleen cells in the presence of 1,25-(OH)2D3 or PGE2 even if devitalized. Incubation of ts8 cells in these agents before devitalization did not avoid the requirement for the presence of PGE2 or 1,25-(OH)2D3 during subsequent incubation with spleen cells. Thus, hematopoietic cells produce sufficient PGE2 for osteoclast formation, and the PGE2 thus produced acts on hematopoietic precursors, which can be induced in the presence of PGE2 to express CTR and resorb bone on contact with osteoclast-inductive stromal cells. The ability of osteoclast-inductive cells to support osteoclast formation appears not to rest on their ability to produce, induce, or respond to PGE2. PMID- 1615763 TI - Risk of fractures in patients with pernicious anemia. AB - In a series of postmenopausal women previously studied by our group, pernicious anemia was associated with reduced bone mineral density of the spine and with vertebral fractures. To determine whether osteoporotic fractures represent an important clinical problem for such patients, we conducted a population-based retrospective cohort study of all Rochester, Minnesota residents newly diagnosed with pernicious anemia from 1950 through 1979. These 131 individuals were followed through the inpatient and outpatient records of all medical care providers in the community for 1550 person-years. In comparison with fracture rates from the general community, patients with pernicious anemia had a 1.9-fold increase in proximal femur fractures, a 1.8-fold increase in vertebral fractures, and a 2.9-fold increase in distal forearm fractures (all p less than 0.05). Increases in the risk of proximal humerus and pelvis fractures were not statistically significant. Clinicians should be aware that pernicious anemia is associated with an increased risk of osteoporotic fractures, but the mechanism is unknown. PMID- 1615764 TI - HLA antigens and intracranial aneurysms. AB - The frequencies of the HLA-A, -B and -DR were determined in a group of 59 transplant donors who died from subarachnoid haemorrhage within three days following the rupture of intracranial aneurysm (the SAH group) and compared with those of a control group consisting of 389 donors who died from other causes. The only significant difference was in the increased frequency in the SAH group of non-typed ("empty")-DR loci in association with the DR7 phenotype. The most probable explanation of this finding is that in the SAH group the frequency of DR7 homozygotes is several times higher than in the general population, and that bearing the DR7 allele in homozygotic form is associated with a very high risk of developing potentially fatal intracranial aneurysmal haemorrhage. PMID- 1615766 TI - Plasma osmolality, osmoregulation and prognosis after head injury. AB - 108 Patients with severe brain damage were examined for the course of plasma osmolality. In addition plasma values of Na+, K+, glucose and blood urea nitrogen (BUN) were measured simultaneously by auto-analyzer. The clinical status was registered daily by using a modified Glasgow coma scale. Outcome of the injured patients was registered by using the Glasgow outcome scale. 60 patients survived, 48 died, 39 of brain damage and 9 of secondary diseases, such as infection or embolism. Sustained severe brain damage is generally followed by disturbances of metabolic regulation. Quite often the osmotic regulation is disturbed. In most cases these disturbances are of hyperosmolar nature, their extent and duration being correlated to the prognosis. Hyposmolar deregulation occurs less frequently, and occasionally lead to peracute brain oedema (e.g. SIADH-syndrome). These dysregulations are interpreted as disturbances of the central function of the diencephalon, in lethal cases even as "hypothalamic death". Blood osmolality measurements should therefore be made early in states of acute cerebral disease to help establish a prognosis, control the treatment of water imbalance and to determine contra-indications to osmotherapy. PMID- 1615765 TI - Stereotactic diagnosis and treatment of pineal region tumours and vascular malformations. AB - Diagnosis and treatment of tumours and vascular malformations in the region of the pineal gland continue to challenge the neurosurgeon's skill. Due to vital vascular and brain structures in the region, microsurgical removal of such masses is often impossible. During the past nine years, we have managed 47 patients with pineal region mass lesions using stereotactic techniques for diagnosis and treatment. In order to determine further therapeutic options, 15 patients underwent stereotactic biopsy of pineal region tumours. In all patients, the histologic diagnosis obtained served to direct further therapy. Thirty-two patients were treated with stereotactic radio-surgery for pineal region tumours or vascular malformations. During the follow-up period, one patient underwent delayed microsurgical resection of a midbrain angiographically occult vascular malformation. No other patient required microsurgical intervention after a stereotactic procedure. In all 47 patients, no significant morbidity or mortality occurred after stereotactic biopsy or radiosurgery. Empiric treatment of pineal region tumours with fractionated radiation therapy is no longer warranted. Image guided stereotactic technology provides a safe method to accurately diagnose and effectively treat selected pineal region masses. After definitive histologic diagnosis is established, proper treatment may be instituted. Options for treatment include stereotactic radiosurgery for selected tumours and vascular malformations, microsurgical resection of benign tumours or fractionated external beam radiation therapy for malignant germ cell and glial tumours. Stereotactic surgery should be the first option in the diagnosis and therapy of pineal region masses. PMID- 1615767 TI - Isoflurane in the management of status epilepticus after surgery for lesion around the motor area. AB - When conventional treatment for status epilepticus fails, general anaesthesia is recommended. We present our experience with isoflurane, an inhalational anaesthetic, in the management of four patients with status epilepticus which occurred soon after surgery for motor area lesion. The seizures were controlled with relatively small concentrations of isoflurane. Hypotension, the only adverse effect of isoflurane, was managed easily with the use of dopamine in physiological saline. Although status epilepticus occurring soon after surgery is transient, it carries a risk of persistent brain damage if active treatment is not instituted promptly. Isoflurane general anaesthesia may be recommended to control it in the intensive neurosurgical care. PMID- 1615768 TI - Diagnosis of cervical disc disease. MRI versus cervical myelography. AB - In a prospective study of 63 surgical patients cervical myelography was compared with MRI to establish the relative value of the 2 diagnostic procedures in patient selection for surgery of ruptured cervical discs and bony nerve root compression. While MRI in the T1-weighted and gradient echo modes matched the diagnostic accuracy of invasive myelography (95%), T1 and T2-weighted MRI images alone were associated with an error rate of 10%. In patients with medial protrusion myelography did not always show the true extent of compression, whereas MRI tended to miss small laterally protruding disc fragments. Cervical myelography continues to have a place in the diagnosis of cervical disc disease, whenever clinical signs and symptoms do not agree with MRI data. PMID- 1615769 TI - Thoracic disc herniation. Analysis of 14 cases and review of the literature. AB - Fourteen cases of thoracic intervertebral disc prolapse are reported and analysed. Eleven were women, 3 men, and the peak incidence was in the 5th decade. No trauma was reported in our cases. The T8/9 interspace was the most frequently involved. A sensory level was noticed in 6 cases and in four a clear cut sensory level at T10 was observed. Results of surgical treatment show that using microsurgical techniques costotransversectomy and its modifications are equally effective; laminectomy is contraindicated. PMID- 1615770 TI - Near-anatomical reduction and stabilization of burst fractures of the lower thoracic or lumbar spine. AB - Thirty-one consecutive symptomatic patients with burst fractures of the lower thoracic or lumbar spine (T 11-L4) were treated by early surgery in a 36-month period, with near-anatomical reduction being achieved via the postero-lateral route. Fusion and reconstruction of the vertebral body was done by using autologous or processed bovine bone. Correction of the kyphotic deformity was obtained by using distraction rods or transpedicular devices. The post-operative mean degree of kyphosis, percent vertebral height, and percent canal stenosis showed statistically significant differences, compared with the corresponding pre operative mean values. All but one of the 25 patients with incomplete paraplegia exhibited neurological improvement, with complete recovery occurring in 20 cases (median follow-up: 16 months) irrespective of the location of the lesion at the thoraco-lumbar junction (T 11-L1) or the lower lumbar segment (L2-L4). Out of the 6 patients with pre-operative complete paraplegia, useful motor power returned in one case with a lesion below L1. The results confirm the suitability of the postero-lateral route and are consistent with the assumption that early near anatomical reduction and stabilization favours maximum neurological recovery in symptomatic patients. PMID- 1615771 TI - Cognitive deficits after rupture and early repair of anterior communicating artery aneurysms. AB - In a retrospective follow-up study covering a time period of four years 18 patients operated upon early for an aneurysm of the anterior communicating artery (ACoA) and a control group of 21 patients with aneurysmal subarachnoid haemorrhage (SAH) from other sources than ACoA aneurysm and 9 patients with SAH of nonaneurysmal origin were subjected to neuropsychological examination. Both groups were comparable in their neurological condition on admission and in the severity of bleeding seen on CT-scan. Testing included memory functions, concentration, logical and spatial thinking, a Stroop-test, an aphasia screening test and a complex choice reaction task. Patients with SAH of a ruptured ACoA aneurysm did not differ significantly from the control group in any of the tests used. But there was a trend for the ACoA patients to have more memory problems than the patients with SAH of other origins. On the other hand the patients in the control group with aneurysmal SAH of other locations and with non-aneurysmal SAH had not significantly more problems with concentration and aphasia than the patients with ruptured ACoA aneurysm. These results, which differ from the common opinion of frequent occurrence of memory deficits in ACoA aneurysms are interpreted as a consequence of the changes in improved pre-, intra- and postoperative management in modern neurosurgery. PMID- 1615772 TI - Significant lateralisation of supratentorial ICP after blunt head trauma. AB - After blunt head trauma simultaneous left and right hemispheric intracranial pressure (ICP) monitoring revealed a pressure gradient of about 30 mmHg persisting until the 5th day after the accident equilibrating thereafter. ICP was elevated over the radiologically more compressed hemisphere. The supratentorial space seems to allow considerable interhemispheric pressure gradients. As a consequence epidural ICP monitoring should be performed over the hemisphere with signs of greater compression. PMID- 1615773 TI - Late posttraumatic nonvascular pulsating eye. AB - A patient is reported with unilateral intermittent pulsating eye caused by the combination of an orbital encephalocele and hydrocephalus, thirty four years after a head injury. Treatment of the hydrocephalus resulted in disappearance of the eye pulsations and encephalocele, as well as in improvement of the gait. PMID- 1615774 TI - Cardiac rehabilitation and elderly patients. PMID- 1615775 TI - A longitudinal study of the occurrence of joint complaints in elderly people. AB - Joint complaints were studied in two cohorts longitudinally followed at 4-5 year intervals between the ages of 70 and 79, representative of the elderly population of Goteborg, Sweden. Joint complaints were reported by 30-43% of the women and by 15-25% of the men. A significant increase of joint complaints was found in both sexes between the ages of 70 and 75 but not thereafter. The knee joints were the most common site of complaints in both sexes. Complaints were not consistently reported by the probands at all examinations, however, and a 'disappearance' of complaints with age was found. Complaints on all three occasions were reported by 15% of the women and 3% of the men. An association was observed between repeatedly reported complaints and radiographic osteoarthritis as well as with self-reported rheumatoid arthritis. PMID- 1615776 TI - Practical problems with eye-drops among elderly ophthalmology outpatients. AB - Many elderly patients have eye-drops prescribed. We have examined the abilities in eye drop application of 43 consecutive outpatients aged 75 years or more who completed a questionnaire and demonstrated their technique in eye-drop application. Less than one-third of patients applied drops themselves, the rest relying on others; one-third of this group lived alone. The majority of patients experienced some difficulty with the application of their drops and it was estimated that half of those who usually applied their own treatment were unlikely to succeed in instilling a drop into the conjunctival sac. Few patients had been prescribed aids or appliances to improve their eye-drop application technique. PMID- 1615777 TI - Quantitative vibration perception testing in elderly people: an assessment of variability. AB - The variability of vibration perception threshold measured by the Biothesiometer for three consecutive readings on a single occasion and 18 sequential readings over 7 days was assessed in 20 elderly convalescent subjects. The coefficient of variation for three consecutive readings at the great toe was high [right great toe: median (range) 15 (6-260%]. The median coefficients of variation for sequential readings were higher than those for consecutive readings at both toes [right great toe: median (range) 26 (5-71)% versus 15 (6-26)%, p = 0.0001]. Thus quantitative tests of sensory function are not reliable in elderly people, even when the subjects have no acute medical problem. Screening for neuropathy in elderly patients should probably rely on clinical examination or electrophysiological tests. PMID- 1615778 TI - Glycosylated haemoglobin in the diagnosis of diabetes mellitus in elderly people. AB - An oral glucose tolerance test (OGTT, 75 g WHO criteria) was applied to healthy elderly subjects (mean age 76 years) within a week of measurement of random blood glucose and glycosylated haemoglobin (HbA1). The 'Corning' method was used to assay HbA1 (established normal range for our laboratory 5-8%). Sixty-five subjects (38 women) of whom 54 were not diabetic on WHO criteria for OGTT participated in the study. Five of the 54 patients with non-diabetic OGTT results had abnormal HbA1 (greater than 8%). These five subjects had no evidence of impaired glucose tolerance. Eleven subjects had diabetic OGTT results of whom only four had raised HbA1 assay results. Seven subjects had normal HbA1 in spite of diabetic OGTT. The mean HbA1 in the group of subjects with normal OGTT (n = 52) was 6.7% (SD 1.05, range 4.6-8.7%). It appears from our study that the normal range of HbA1 in elderly subjects is not markedly different from established normal values. The poor sensitivity (36%) and predictive value (44%) of abnormal HbA1 in detecting diabetes, as shown in our study, would not permit its use for screening purposes nor as a confirmatory test for diabetes in elderly subjects. PMID- 1615779 TI - Elderly patients and their medication: a post-discharge follow-up study. AB - Fifty-six elderly patients (age range 65-98 years) discharged from a geriatric unit were visited at home on or after the 5th post-discharge day (median day 8) and their medication assessed. By the day of the visit, 15 of the 56 had not had a new prescription issued (27%) and 27 patients (48%) had old prescribed medication at home. Forty-one new scripts, issued by general practitioners, should have contained 128 medications if the general practitioners wished to continue unchanged the medication given on hospital discharge. Fourteen drugs (11%) had been added and 17 drugs (13%) omitted. The number of prescriptions issued unchanged was 26/41 (63%). Inaccurately labelled containers and/or changed drug names were found in 28%. Contrary to hospital advice, 47% of medications were issued in childproof containers. Poor communication between hospital and general practitioners is only part of the problem. Methods to expedite the delivery of new prescriptions should be developed. PMID- 1615781 TI - Reduced axial rotation in the spouses of sufferers from clinical idiopathic parkinsonism. AB - Axial rotation during recumbency was used to quantify the tendency towards parkinsonism with respect to one cardinal sign, brady/hypokinesia. Twenty-four elderly sufferers from idiopathic parkinsonism, their spouses, and 40 control subjects were studied. Significant differences in total angular displacement over 7 h were found between sufferers and their spouses (83% of grand mean) and between spouses of sufferers and controls (31%). These differences could not be accounted for by age or cognitive function. Moreover, the total angular displacement of the spouses was independent of whether they shared a bed with the sufferer. Neither the sufferers and their spouses, nor the 20 couples who constituted the control group, showed any relationship between partners with respect to angular displacement. These findings do not favour learned behaviour, or selective mating as an explanation of reduced movement in spouses of sufferers. Significantly more of the control couples had a single cardinal sign in both partners than expected on the basis of the frequency of a single sign in one partner. Environmental factors operating in adult life could be involved in the pathogenesis of parkinsonism. PMID- 1615780 TI - Immunogenicity of inactivated influenza vaccine in residential homes for elderly people. AB - One hundred and seventy residents of 11 Leicester City Council homes for the elderly, with a total of 515 beds, were studied during a 30-week period from September 1988 to March 1989 to determine the use of influenza vaccine, the levels of influenza antibody, the incidence of influenza, and the protection afforded by vaccination. The study group of 133 women and 37 men had a mean age of 85 years and 59% had one or more chronic medical conditions. The immunization rates by home for the 170 symptomatic residents ranged from 8% to 90% (mean 45%). Seventy-one sera, 36 from vaccinated and 35 from non-vaccinated residents were collected between 1 December 1988 and 24 March 1989 and were assayed for antibody to A/Taiwan/1/86 (H1N1), A Sichuan/2/87 (H3N2) and B/Beijing/1/87. Analysis revealed no statistically significant differences between the antibody profiles of vaccinated and unvaccinated subjects. Six influenza A and 6 influenza B infections were confirmed among the 170 subjects with upper respiratory tract infections. Influenza vaccination was not associated with significant levels of protection against influenza A or B. Studies of the haemagglutinins of the vaccine strains and influenza isolates during 1988/89 showed that they were closely related. PMID- 1615782 TI - Characteristics of urinary incontinence in elderly patients studied by 24-hour monitoring and urodynamic testing. AB - Characteristics of urinary incontinence have been studied in 100 elderly incontinent patients using invasive video-urodynamics and noninvasive 24-h monitoring of incontinence, fluid intake, voiding and residual urine. Incontinence was of the urge type in 51 patients, including 24 with reduced bladder sensation. Noninvasive 24-h monitoring showed satisfactory reproducibility and high sensitivity (88%) for detecting urine loss. Urodynamically proven urge incontinence, especially in combination with reduced sensation, and recent bacteriuria were associated with severe urine loss on 24-h monitoring. On 24-h monitoring, urine output was significantly larger at night and nocturia was common. In urge incontinence urine loss was predominantly nocturnal and the amount depended significantly on the previous evening's fluid intake and on nocturia. Noninvasive 24-h monitoring showed that post-void residual was common and was often largest in the early morning. It also yielded many free-voiding flow curves. Normal flow curves with small residual urine make dysfunction of voiding itself unlikely. Thus noninvasive monitoring provides information about incontinence and voiding that is suitable for designing intervention and management strategies. Invasive testing may be necessary however to confirm the urodynamic type of incontinence or suspected voiding dysfunction. PMID- 1615783 TI - Use of cisplatin for elderly patients. AB - The ageing of the population has resulted in a greater emphasis on cancer treatment effects in elderly patients. This population has often had arbitrary dose modification of chemotherapy owing to fear of excessive side-effects. A review was undertaken to evaluate cisplatin toxicity in patients of 70 years of age or older. Thirty-four patients were evaluated. Their mean age was 72.8 years and 85.3% were women. Fourteen of 34 (41%) patients completed the planned therapy. Treatment was terminated because of disease progression (35%), renal toxicity (9%) and non-renal toxicity (15%). Our conclusion is that cisplatin can safely be administered to elderly patients. Arbitrary dose modification or elimination of cisplatin from a treatment programme on the grounds of patient age alone is not justified. PMID- 1615784 TI - Dementia in Melton Mowbray--a validation of earlier findings. AB - In 1981 a survey of elderly persons aged 75 years and over who belonged to a general practice in Melton Mowbray, Leicestershire found a prevalence of moderate cognitive impairment of 4.7%. The criterion which determined the impairment was a score of 7 or under on the CAPE Information/Orientation (IO) sub-test. The prevalence rate has been considered to be much lower than in some key studies, notably the 13% reported in 1970 from Newcastle upon Tyne. Although rates based on cognitive scales are likely to give different results from those based on diagnostic assessment, the suggestion is that the IO sub-test is an insensitive screening instrument for dementia. Using results on the sensitivity and specificity of the CAPE IO sub-test (cut-point 8/9) to detect moderate or severe dementia as defined by clinical diagnosis using the Cambridge Mental Disorders of the Elderly (CAMDEX) schedule, the adjusted prevalence rates of moderate or severe dementia were found to be 3.4% in 1981 and 5.2% in 1988. Both these figures were lower than the observed rates scoring 8 or under on the IO sub-test, confirming that insensitivity of the IO sub-test was not the reason for the supposed low rate in Melton Mowbray in 1981. As the prevalence of dementia in those aged 75 years and over has been reported by other studies to range from 3% to 24%, it is more likely that high rates are due to screening instruments with low specificity. PMID- 1615785 TI - Urinary and faecal incontinence in community-residing elderly women. AB - The prevalence of urinary and faecal incontinence was investigated in a sample of 1049 women aged 60 years and over in the municipality of Amstelveen, the Netherlands; 719 postal histories were completed. The overall prevalence of urinary incontinence was 23.5%. Daily urine loss was reported by 14.0% of all women. In women aged 60 to 84 years and 85 years and over 4.2% and 16.9% were faecally incontinent, respectively. In all age groups poor mobility and frequency were associated with urinary incontinence. Urgency was independently associated in women aged 60-85 years as was nocturia in women aged 85 years and over. PMID- 1615786 TI - Bacterial meningitis in elderly patients: clinical picture and course. AB - We reviewed the case records of 48 patients aged 60 years and older with a diagnosis of acute bacterial meningitis made during the period 1976-88. Predisposing conditions were present in 26 patients (54%) and concurrent infections in 24 patients (50%). Streptococcus pneumoniae accounted for 41% of all isolates and 56% were Gram-positive organisms. The most common symptoms were fever (79%), meningism (54%) and change in mental status (69%). Sixty-three per cent of the patients survived. Increased fatality was associated with absence of typical symptoms and signs and was presumably due to a delay in diagnosis. Other clinical and biochemical variables and antimicrobial therapy before admission to hospital and the presence of underlying disease were not associated with outcome. PMID- 1615787 TI - Hypothesis: age-associated changes in gait represent, in part, a tendency towards parkinsonism. AB - In 144 healthy, active, asymptomatic volunteers (aged 30-88 years), age explained 33% of the variance in free walking speed. This could not be ascribed simply to differences in physique at maturity, since height had a more important effect on speed (p less than 0.0001) than did leg length (p less than 0.01). Multiple linear regression was used to fit models for speed, by selection from four sets of variables: common physical, body sway, functional anatomy of spine and lower limbs, and psychometric. The best model (which included age) explained little more of the variance (41%) than did age alone. Moreover, incorporation of age into the alternative model, built in its absence, still contributed significantly (p less than 0.0001) to the variance explained. The effect of age on gait appeared to be complex, with an increment in double support time disproportionate to the reduction in speed. We formulate by exclusion, the hypothesis that age associated changes in gait represent, in part, a tendency towards parkinsonism. PMID- 1615788 TI - 'Eye tests' and elderly people. PMID- 1615789 TI - Medications, fallers and non-fallers. PMID- 1615790 TI - Management and immediate outcome of patients with intracoronary thrombus during percutaneous transluminal coronary angioplasty. AB - A retrospective analysis of our experience with intraprocedural thrombus complicating percutaneous transluminal coronary angioplasty (PTCA) was undertaken. Of 983 PTCA procedures reviewed, 62 (6.3%) were complicated by thrombus. Patients were managed conservatively (group I, n = 18), with redilation (group II, n = 17), or with intracoronary urokinase and redilation (group III, n = 27). The three groups did not differ with respect to demographic or baseline angiographic variables, but complications, defined as death, myocardial infarction, bypass surgery, or threatened occlusion requiring emergency stenting, occurred in 11% of patients in group I, 24% in group II, and 48% in group III. Occlusive thrombus behavior was observed in 80% of these 62 patients. Patients with complications were less likely to have received antecedent antiplatelet therapy (79% vs 95% of patients without complications), had more complex baseline lesion morphology, more often had thrombus present at baseline (42% vs 19%), and more often had a low activated clotting time at the start of PTCA (53% vs 8%). Thrombi that led to complications more frequently exhibited occlusive behavior before therapy was begun (95% vs 71%) and more often occurred in the setting of intimal dissection (42% vs 14%). Patients undergoing PTCA at the time of diagnostic catheterization were more likely to have complications than those in whom PTCA was delayed. A successful outcome was more likely (83% vs 27%, p = 0.03) in group III if at least 140,000 U of urokinase were administered within 50 minutes of the appearance of thrombus. Thus intracoronary thrombus formation during PTCA remains a significant source of morbidity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615791 TI - Effects of acute and prolonged administration of propafenone on internal defibrillation in the pig. AB - Some antiarrhythmic sodium channel blocking drugs have been found to increase the energy necessary for internal defibrillation. Propafenone is a new drug that has been shown to be efficacious in the therapy of supraventricular and ventricular arrhythmias, and is of potential use in patients with defibrillators. The effects of short-term and prolonged propafenone administration on the internal defibrillation threshold (DFT) were determined in 43 pigs randomized to one of four groups: saline infusion (n = 10); propafenone infusion (n = 10); placebo administration for 8 days (n = 10); or propafenone administration for 8 days (n = 13). Two mesh electrodes were sutured on the right lateral and left lateral epicardial surface and current was delivered from the right electrode to the left electrode. Triplicate DFTs were obtained before and at 40 and 80 minutes after infusion of drug or placebo. In pigs receiving long-term administration, after baseline DFTs were obtained the electrodes were removed and the chest was closed. Following 8 days of drug or placebo administration, DFTs were redetermined. No changes were observed in the short- or long-term control groups. DFTs were lower after propafenone administration: either short-term infusion (20 +/- 6.2 joules at baseline; 15.6 +/- 5 joules at 40 minutes, p less than 0.05; 10.2 +/- 6 joules at 80 minutes, p less than 0.001) or long-term administration (17.8 +/- 2.6 joules at baseline versus 12 +/- 3.2 joules on drug, p less than 0.002). Decreased ventricular cycle lengths were found with acute administration of propafenone. Three pigs died during long-term administration of propafenone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615792 TI - Flecainide single oral dose for management of paroxysmal supraventricular tachycardia in children and young adults. AB - The efficacy of a single oral dose of flecainide to terminate paroxysmal supraventricular tachycardia (PSVT) was evaluated in 25 children and young adults. The subjects were selected from a group of 35 patients with recurrent attacks of PSVT evaluated by means of electrophysiologic study and intravenous electropharmacologic testing with flecainide. In all 25 patients the induced PSVT was stopped by intravenous flecainide and was then no longer inducible or nonsustained. All patients had normal hearts. At least 48 hours after acute intravenous testing, 25 patients underwent electrophysiologic study with a transesophageal catheter and PSVT was induced in all of them: atrioventricular reentrant tachycardia in 16 and atrioventricular nodal reentrant tachycardia in nine. During stable tachycardia, a single oral dose of flecainide (2.9 +/- 0.3 mg/kg; 2.5 to 3.3 mg/kg) was administered. This approach was effective for termination of PSVT in 22 patients. The mean plasma level of flecainide at cessation of tachycardia was 277 +/- 92 ng/ml (150 to 500 mg/ml). All 22 patients who responded were given a single oral dose of flecainide for recurrences of PSVT during follow-up. During a period of 12 +/- 7 months (2 to 27 months) a total of 134 spontaneous episodes of PSVT were reported, and 127 of these episodes were terminated with periodic management. Thus oral periodic flecainide seems useful for management of PSVT in selected patients. PMID- 1615793 TI - Risk assessment in nonischemic ventricular arrhythmia by left and right ventriculography. AB - Ventricular fibrillation and sudden death are rare phenomena in nonischemic ventricular arrhythmia, particularly in arrhythmogenic right ventricular cardiomyopathy. In most instances electrophysiologic studies help to assess the risk of sudden death, but sometimes programmed ventricular stimulation is unsuccessful. Among 48 patients with ventricular fibrillation (n = 9) and sustained (n = 25) and nonsustained (n = 19) ventricular tachycardia, invasive and noninvasive diagnostic tests (coronary angiography, biventricular angiography, programmed ventricular stimulation, and echocardiography) were performed to obtain more information about the underlying heart disease. In 43 patients (90%) arrhythmogenic right ventricular cardiomyopathy was diagnosed with segmental hypokinesia (n = 31) and diffuse hypokinesia (n = 12) of the right ventricle. In patients with documented ventricular fibrillation, the right ventricular ejection fraction was lower (30.8% vs 47.8% and 45.9%, respectively) and multisegmental contraction impairment of the right ventricle was significantly more frequent (p less than 0.001). Additional left ventricular abnormalities and right ventricular dilatation were not significant parameters for identifying high-risk patients. In addition to programmed ventricular stimulation, quantitative analysis of the results of right and left ventricular angiography contributes to risk assessment in patients with nonischemic ventricular arrhythmia. PMID- 1615794 TI - Significance of aborted cardiac arrest and sustained ventricular tachycardia in patients referred for treatment therapy of advanced heart failure. AB - Cardiac arrest in patients with heart failure may be the result of remediable factors such as pulmonary edema, drug toxicity, or electrolyte abnormalities, or it may be due to primary arrhythmias. The relation of prior aborted cardiac arrest or sustained ventricular tachycardia to subsequent prognosis was assessed in 458 consecutive patients referred for management of advanced heart failure (left ventricular ejection fraction 0.2 +/- 0.07). All patients received tailored vasodilator and diuretic therapy and were then followed as outpatients. Patients were divided into four groups: 388 patients (85%) with no prior cardiac arrest or sustained ventricular tachycardia, 31 patients (7%) with a primary arrhythmia cardiac arrest, 22 patients (5%) with a secondary cardiac arrest, and 17 patients (4%) with sustained ventricular tachycardia without cardiac arrest. Patients with cardiac arrest resulting from a primary arrhythmia were usually treated with antiarrhythmic drugs (25 patients), and five patients received an implantable defibrillator. After hospital discharge actuarial 1-year sudden death risk (17%) and total mortality (24%) rates for the group with primary arrhythmia were similar to corresponding values in patients with no history of cardiac arrest or sustained ventricular tachycardia (17% and 30%, respectively). In patients with a secondary cardiac arrest as a result of exacerbation of heart failure (11 patients), torsade de pointes (10 patients), or hypokalemia (one patient), therapy focused on removal of aggravating factors. Actuarial 1-year sudden death (39%) and total mortality (54%) rates for the group with secondary arrest were higher than for patients without a history of cardiac arrest (p = 0.003 and 0.005, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615795 TI - Coronary angioplasty in patients eighty years of age or older. AB - Percutaneous transluminal coronary angioplasty (PTCA) was performed on 58 lesions in 53 patients 80 years of age or older with unstable angina. Most patients had previous myocardial infarction, abnormal left ventricular contraction patterns, and multivessel coronary disease. In most (48) patients only one vessel was dilated. PTCA was successful in 48 (82.8%) lesions, but complications were frequent. Eight patients died, six after anatomically successful PTCA (three with cardiac complications, two with noncardiac complications, and one with both cardiac and noncardiac complications). Two patients died after unsuccessful PTCA (one of cardiac complications and one of noncardiac complications), and 11 patients with PTCA were alive with significant complications (all noncardiac). Twenty-nine patients had successful PTCA with no complications; 40 (74.5%) patients were discharged with clinically successful PTCA. It is concluded that PTCA is feasible in patients 80 years of age or older but that both cardiac and noncardiac complications are common in this group of very fragile patients. PMID- 1615796 TI - Determinants of the renal response to ACE inhibition in patients with congestive heart failure. AB - The objective of the present study was to determine whether pretreatment neurohormonal and renal hemodynamic parameters predict the change in renal function with the administration of quinapril, a new angiotensin-converting enzyme (ACE) inhibitor. Twenty patients with New York Heart Association (NYHA) class III and IV heart failure were evaluated. Following pretreatment determination of renal function and plasma neurohormones, patients were treated daily with 10 mg of quinapril. Measurements of glomerular filtration rate (GFR) and renal plasma flow (RPF) were repeated after 7 weeks to assess changes in function (delta GFR and delta RPF). Mean GFR increased from 49 +/- 6 to 56 +/- 7 ml/min/1.73 m2 (p = 0.10), but decreased in five patients. Mean RPF increased from 235 +/- 23 to 252 +/- 23 ml/min/1.73 m2 (p = 0.08), but decreased in five patients. There was no relation between delta GFR and baseline determinations of GFR, RPF, plasma renin activity, plasma angiotensin II, or serum Na. Only a high filtration fraction (GFR/RPF) predicted a decreased GFR (r = 0.61, p less than 0.005). In contrast, no baseline renal hemodynamic parameter correlated with delta RPF. We conclude that poor renal function does not increase the risk of renal deterioration with quinapril. However, dependence of renal function upon the renin-angiotensin system may be predicted by a high filtration fraction. PMID- 1615798 TI - Abnormalities of diastolic filling of the left ventricle associated with aging are less pronounced in exercise-trained individuals. AB - To determine whether exercise training has an effect on left ventricular diastolic dysfunction associated with the normal aging process, we studied a group of 20 normal healthy adult distance runners (mean miles currently run per week was 45 for an average of 15 years) and 20 normal healthy sedentary individuals (who currently walk less than 1 mile per day and are not involved in a regular exercise program) matched for age and systolic and diastolic blood pressure with the runners. Doppler echocardiographic indices of left ventricular diastolic filling were significantly different between the two groups. The exercise group when compared with the sedentary group had significantly decreased late diastolic peak filling velocity (0.51 +/- 0.11 m/sec versus 0.66 +/- 0.20 m/sec; p = 0.003), late diastolic velocity-time integral (5.2 +/- 1.5 cm versus 6.6 +/- 2.2 cm; p = 0.02), increased early-to-late peak filling velocity ratio (1.29 +/- 0.38 versus 0.96 +/- 0.24; p = 0.001), and early-to-late velocity-time integral ratio (2.08 +/- 0.51 versus 1.42 +/- 0.47; p less than 0.001). We conclude that the left ventricular diastolic dysfunction associated with "normal" aging is less pronounced in those persons who are exercise-trained. PMID- 1615797 TI - Reduced pulmonary microvascular permeability in severe chronic left heart failure. AB - Pulmonary edema is a serious complication of heart failure, but often patients with chronic heart failure resist pulmonary edema despite elevated pulmonary venous pressures. This protection might be a result of decreased pulmonary microvascular permeability. Double-isotope scintigraphy with 113mindium-labeled transferrin and 99mtechnetium-labeled erythrocytes allows noninvasive estimation of pulmonary microvascular permeability; an index of transferrin accumulation is calculated that reflects microvascular permeability. Fourteen patients with severe chronic left ventricular dysfunction were compared with a control group of 15 patients with mild coronary artery disease. In the control group the transferrin accumulation index was 0.35 (range -0.3 to 1.0) x 10(-3)/min, and in patients with heart failure the index was 0.0 (range -1.0 to 0.7) x 10(-3)/min, which was significantly lower (p less than 0.01). The reduction in the transferrin accumulation index correlated weakly with the duration of heart failure (R = -0.5, p less than 0.02). These data indicate reduced protein efflux consistent with a decrease in pulmonary microvascular permeability in patients with severe chronic heart failure. Similar changes have been observed in severe mitral stenosis and may reflect a generalized adaptation to chronic pulmonary venous hypertension. PMID- 1615799 TI - Risk factors for systemic embolism in patients with paroxysmal atrial fibrillation. AB - The purpose of this study was to define the risk factors for systemic embolism in patients with recently diagnosed paroxysmal atrial fibrillation. We therefore studied 63 consecutive patients with symptomatic nonvalvular paroxysmal atrial fibrillation and performed a clinical and noninvasive cardiac, peripheral vascular, and neurologic evaluation that included two-dimensional echocardiography, 24-hour Holter monitoring, and computed tomographic brain scan. Patients with predisposing clinical conditions for systemic embolism (valvular heart or coronary artery disease) or paroxysmal atrial fibrillation (sick sinus disease, preexcitation, or thyroid dysfunction) were excluded. At entry 34 patients had idiopathic paroxysmal atrial fibrillation and 29 had hypertension. Fourteen patients had a recent systemic embolic complication: nine had a recent occlusive nonlacunar cerebrovascular accident, two had transient ischemic attacks, and three had peripheral systemic emboli that required surgery. In addition, five patients had evidence of old cerebrovascular accident on the computed tomographic scan (group 1). Forty-four patients had no systemic embolism (group 2). Results of univariate analysis showed that patients in group 1 were older (72 +/- 9 vs 63 +/- 13 years, p less than 0.05), had a higher incidence of hypertension (70% vs 35%, p less than 0.01), and had an increased left atrial diameter (4.1 +/- 0.7 vs 3.6 +/- 0.5 cm, p less than 0.05). Multiple stepwise logistic regression analysis showed that a history of hypertension and left atrial enlargement on two-dimensional echocardiography were significant independent risk factors for systemic embolism in patients with symptomatic nonvalvular paroxysmal atrial fibrillation. PMID- 1615800 TI - Ten-year experience with mitral valve replacement in the elderly. AB - Limited data are available on mitral valve replacement in the elderly patient. Therefore we report our 10-year experience including predictors of perioperative mortality and subsequent long-term cardiac mortality in elderly patients with mitral valve replacement compared to younger patients. Of the 126 consecutive patients with mitral valve replacement, 26 were older (77 +/- 4, group 1) and 100 were younger (62 +/- 9, group 2) than 70 years. Bioprostheses were used more frequently in patients in group 1 (65% vs 7%, p less than 0.0001). Of the 21 clinical, ECG, hemodynamic, and angiographic variables studied, patients in group 1 had higher pulmonary artery systolic pressure (57 +/- 15 vs 48 +/- 19, p less than 0.05), fascicular block on ECGs (70% vs 33%, p less than 0.005), and greater pump time on cardiopulmonary bypass (160 +/- 75 vs 120 +/- 50 minutes, p less than 0.025). A trend toward a higher perioperative mortality rate was also seen in group 1 (27% vs 12%, p = 0.058). Predictors of perioperative mortality by multivariate analysis were the presence of aortic calcification and prolonged pump time on cardiopulmonary bypass in group 1 and coronary artery disease, female sex, elevated mean pulmonary artery pressure, and postoperative complete atrioventricular block in group 2. During a mean 4-year follow-up period, cardiac mortality and total mortality rates were 42% and 54%, respectively, for group 1 compared to 24% and 35%, respectively, for group 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615801 TI - Factors influencing immediate results, complications, and short-term follow-up status after Inoue balloon mitral valvotomy: a North American multicenter study. AB - Clinical trials with the Inoue mitral valvotomy balloon have recently begun in the United States. We assessed the effects of 17 demographic, echocardiographic, procedural, and hemodynamic variables on the immediate results, complications, and short-term follow-up of 200 patients in 15 centers undergoing valvotomy with this device. The study population had a mean age +/- SD of 53 +/- 15 years, and the total echocardiographic score was 7.2 +/- 2.4. Valvotomy was technically successful in 96.5% of procedures and increased the mean mitral valve area from 1.0 +/- 0.3 to 1.8 +/- 0.7 cm2 (p less than 0.001); 72% had an increase in valve area greater than or equal to 50%, and 67% had a final area greater than or equal to 1.5 cm2. Major procedural complications included cardiac tamponade during transseptal puncture (1.0%), systemic embolism (1.5%), and severe mitral regurgitation (2.4%); there were no procedural deaths and one hospital death. Multivariate analysis identified the absence of prior surgical commissurotomy and younger age as significant predictors of the gain in mitral valve area, but the correlation coefficients were low. Although the absence of subvalvular disease on echocardiograms was a predictor of a final valve area greater than or equal to 1.5 cm2, the total echocardiographic score did not correlate well with the immediate outcome (r = 0.01, p = NS). No variable was identified as predictive of restenosis, which occurred according to echocardiographic criteria in 14 of 66 (21%) patients evaluated 6 months after valvotomy. Good hemodynamic results with valvotomy were achieved in the majority of patients with low complication rates by many investigators with the use of the Inoue balloon device.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615802 TI - Echocardiographic estimation of balloon-stretched diameter of secundum atrial septal defect for transcatheter occlusion. AB - Stretched diameter of the atrial septal defect (ASD), determined by balloon sizing at cardiac catheterization, is commonly used to select the sizes of the devices used for transcatheter closure of the secundum ASD. We have previously evaluated the utility of pulmonary/systemic flow ratio and angiographic and echocardiographic (echo) sizes of the ASD in estimating stretched ASD diameter in a group of 16 patients and determined that echo diameter had the best correlation with stretched diameter (r = 0.82; p less than 0.001). The stretched diameter can be estimated: 1.05 x echo diameter in millimeters + 5.49. In this study we have prospectively evaluated this formula in estimating the stretched ASD diameter by two-dimensional echo measurements obtained in two (long and short-axis) subcostal views in another group of 21 patients aged 2.5 to 29 years (median 4.5 years). The echo size of the ASD was 9.7 +/- 3.0 mm, whereas the measured stretched diameter was 15.3 +/- 4.0 mm. The predicted stretched ASD diameter was calculated according to the above formula and was 15.7 +/- 3.1 mm, not significantly different (p greater than 0.1) from the measured stretched diameter. The correlation between predicted and measured stretched ASD sizes was excellent (r = 0.9; p less than 0.001). The mean squared error was 2.4. The differences between measured and predicted values were within 2 mm in all but three patients. It is concluded that stretched ASD diameter can be estimated accurately by two dimensional subcostal echo measurements, which in turn could be used for selection of device size for occlusion of the ASD. PMID- 1615803 TI - Noninvasive evaluation of interventricular pressure gradient across ventricular septal defect: a simultaneous study of Doppler echocardiography and cardiac catheterization. AB - Simultaneous continuous-wave Doppler echocardiography and left- and right-sided cardiac pressure measurements were performed during cardiac catheterization in 64 patients with a congenital ventricular septal defect (VSD). The peak-to-peak pressure gradient across the VSD on cardiac catheterization ranged from 0 to 109 mm Hg (61 +/- 31.7 mm Hg). The peak shunt velocity and peak pressure gradient across the VSD on Doppler ultrasound imaging ranged from 0.96 to 5.21 m/sec (3.75 +/- 1.16 m/sec) and from 4 to 105 mm Hg (62 +/- 29.8 mm Hg), respectively. Doppler measurements of the peak interventricular pressure gradient correlated well with measurements obtained by cardiac catheterization (r = 0.98, standard error of estimate = 6.3 mm Hg, p less than 0.001). Doppler ultrasound imaging yielded information comparable to that obtained by catheterization and provided an accurate method of measuring the pressure gradient across the VSD, which is a useful parameter for the assessment of pulmonary artery systolic pressure in patients with a VSD, without a left or right ventricular outflow tract obstruction. PMID- 1615804 TI - Recurrent myocardial ischemia following thrombolytic therapy: guidelines for practicing clinicians. AB - The natural history of patients with acute myocardial infarction treated with thrombolytic therapy includes two distinct phases: the initial or acute phase is characterized pathologically by atheromatous plaque rupture and thrombotic coronary arterial occlusion, and clinically by the abrupt onset of symptoms. Prompt restoration of coronary blood flow and myocardial reperfusion during this phase, achieved in a majority of patients given thrombolytic therapy, limits myocardial necrosis, preserves ventricular function, and lowers mortality. Although the thrombus can be pharmacologically removed, an unstable anatomic substrate persists. Therefore following thrombolytic therapy, a subacute phase occurs, during which patients are at risk for recurrent ischemic events. More than a theoretical concept, experience has shown that recurrent ischemia and reinfarction develop in 20% to 30% and 5% of patients, respectively. Morbidity and mortality are elevated considerably in these patients, dictating an aggressive diagnostic and treatment approach. PMID- 1615805 TI - Significance of preinfarction angina for preservation of left ventricular function in acute myocardial infarction. AB - The effect of preinfarction angina on the preservation of left ventricular function was evaluated with the use of cineventriculography in 37 patients who had either total or subtotal occlusion of the proximal left anterior descending coronary artery during the convalescent period of myocardial infarction. In 15 patients who had preinfarction angina more than 1 week before the onset of acute myocardial infarction (group A), the global left ventricular ejection fraction was 54 +/- 3% (SEM) and regional wall motion in the infarct area was 10 +/- 3%. In 10 patients who had preinfarction angina occurred within 1 week before the onset of acute myocardial infarction (group B), the left ventricular ejection fraction and regional wall motion in the infarct area were 42 +/- 3% and 1 +/- 2%, respectively. In 12 patients without preinfarction angina (group C), the left ventricular ejection fraction and regional wall motion in the infarct area were 38 +/- 3% and -1 +/- 2%, respectively. In groups B and C, both the left ventricular ejection fraction and regional wall motion in the infarct area were lower than those in group A (p less than 0.05). The collateral circulation at the onset of acute myocardial infarction was better in group A compared with groups B and C (p less than 0.05). Thus the collateral circulation, promoted by repetitive anginal episodes indicative of myocardial ischemia, causes the preservation of myocardial function. PMID- 1615806 TI - Atherosclerotic saphenous vein grafts treated with different interventional procedures assessed by intravascular ultrasound. AB - Intravascular ultrasound imaging of saphenous vein grafts may enhance the angiographic interpretation of results following transcatheter interventions. We used intravascular ultrasound to study 18 patients with stenotic vein grafts following balloon angioplasty, atherectomy, or stent placement. In real-time imaging the three-layer appearance was rarely seen, calcification was infrequent (11% of patients), and atheroma were usually mildly echogenic ("soft"). Despite excellent angiographic results (reduction in percent diameter stenosis from 90 +/ 8% to 17 +/- 8%) and concordant improvement in lumen area by ultrasound regardless of the intervention, there was usually significant retained atheroma at the treatment site. Following balloon angioplasty, ultrasound showed multiple superficial fissures and fractures without discrete dissections. Atherectomy caused a smooth lumen surface without deep dissections or resections, but significant retained atheroma was observed with each one of the atherectomy procedures. Endovascular stents were concentric in the vein with reflective struts above compressed atheroma and an outer echogenic adventitia. Stent expansion was asymmetric axially and longitudinally and evidence of stent recoil was present. Thus intravascular ultrasound may be an important adjunct to angiography in characterizing postintervention results in saphenous vein grafts. PMID- 1615807 TI - The white blood cell count and risk for coronary heart disease. AB - In conclusion, the WBC count has been demonstrated in several epidemiologic studies to be a strong independent predictor of future coronary heart disease. Although it is not possible at this point in time to be certain that the elevated WBC count is a cause rather than a consequence of ischemic heart disease, recent pathophysiologic studies suggest that the white blood cell, in particular the neutrophil, is instrumental in the pathogenesis of myocardial ischemia. It is conceivable that patients who develop acute myocardial ischemia have abnormal leukocyte function before the onset of the acute event, which provides a pathophysiologic milieu for the progression of the atherosclerotic process. Future research must focus on further elucidation of the properties of WBCs and clarification of the role of the activated neutrophil in the process of vascular injury. Quantitative and qualitative changes in leukocyte function may have important implications in the development of CHD. PMID- 1615808 TI - Combined rotational and directional atherectomy guided by intravascular ultrasound in an occluded vein graft. PMID- 1615809 TI - Angioplasty in a child with Kawasaki disease. PMID- 1615810 TI - Coronary heart disease in young age associated with essential thrombocythemia. PMID- 1615811 TI - Anomalous origin of the left coronary artery from the pulmonary artery: report of an adult with ventricular fibrillation as the presenting symptom. PMID- 1615812 TI - The ligamentum arteriosum: an unreported origin of peripheral emboli diagnosed by transesophageal echocardiography. PMID- 1615813 TI - Aortic endocarditis after percutaneous balloon valvuloplasty: the role of transesophageal echocardiography in early detection and follow-up. PMID- 1615814 TI - Unruptured sinus of Valsalva aneurysm diagnosed by transesophageal echocardiography. PMID- 1615815 TI - Primary malignant mesothelioma of the pericardium. PMID- 1615816 TI - Low-dose calcium pretreatment to prevent verapamil-induced hypotension. PMID- 1615817 TI - Cocaine-induced bradyarrhythmias. PMID- 1615818 TI - Peaks of QTc lengthening measured in Holter recordings as a marker of life threatening arrhythmias in postmyocardial infarction patients. PMID- 1615819 TI - QT prolongation with torsade de pointes in pheochromocytoma. PMID- 1615820 TI - Multiple emboli from a large aortic arch thrombus in a patient with thrombotic diathesis. PMID- 1615821 TI - Serial documentation of changes in a mitral valve vegetation progressing to abscess rupture and fistula formation by transesophageal echocardiography. PMID- 1615822 TI - Congenital isolated pulmonary valve incompetence: neonatal presentation and early natural history. PMID- 1615823 TI - The role of exercise testing for evaluating patients with unstable angina. PMID- 1615824 TI - Cardiac emergencies at a major international airport: a prospective observational study. PMID- 1615825 TI - Statistical analysis of clinical risk factors for coronary artery spasm: identification of the most important determinant. AB - Coronary artery spasm plays an important role in acute ischemic events, and it has a close relationship with coronary atherosclerosis. Thus we attempted to determine the most significant risk factor for coronary artery spasm. Among 3000 consecutive patients who underwent coronary cineangiography with ergonovine maleate testing, 330 with typical angina pectoris (group 1) and 294 with old myocardial infarction (group 2) were studied. We divided each group into three or four subgroups according to the presence of fixed organic stenosis (FOS+) or a positive reaction to ergonovine maleate (coronary artery spasm [CAS]+). We examined the relationship between coronary artery spasm and eight coronary risk factors: age, sex, hypertension, diabetes mellitus, smoking, and serum cholesterol, uric acid, and high-density lipoprotein cholesterol levels. The proportion of smokers in the subgroups with CAS(+) was significantly higher than in the subgroups with CAS(-)(p less than 0.01). There was no correlation between smoking and fixed organic stenosis. According to the results of multiple regression analysis, there was a positive correlation between smoking and CAS(+) and between serum high-density lipoprotein cholesterol levels and CAS(+)(p less than 0.01). Thus we concluded that smoking is the most significant risk factor in discriminating between patients with and without coronary artery spasm. PMID- 1615826 TI - Induction of coronary artery spasm by intracoronary acetylcholine: comparison with intracoronary ergonovine. AB - To investigate the mechanism of coronary spasm, we compared the action of acetylcholine with that of ergonovine in 11 patients with vasospastic angina (group 1) and in 15 patients with chest pain (group 2). Coronary arteriography was performed immediately after the patients received intracoronary injections of titrated increments of each agent. In the patients in group 1 occlusive or near occlusive (99% luminal narrowing) coronary spasm associated with angina and ischemic electrocardiographic ST changes was noted in nine of 11 patients receiving acetylcholine and in all 11 patients receiving ergonovine. The region and the degree of the most severe coronary spasm on coronary arteriograms evoked by the two agents were the same in nine of the 11 patients in group 1. In the other two patients in group 1, spontaneous focal coronary spastic stenosis in the baseline coronary arteriogram was relieved by the intracoronary injection of acetylcholine, and a focal coronary occlusive spasm in the same region was induced repeatedly by the subsequent intracoronary injection of ergonovine (paradoxic phenomenon). In contrast, occlusive or near-occlusive coronary spasm was not induced by either agent in any patient in group 2. These results suggest that the two provocative tests for coronary spasm that involve acetylcholine and ergonovine are clinically useful in the diagnosis of vasospastic angina, but testing with intracoronary ergonovine is needed when a spontaneous focal coronary spasm is relieved by the intracoronary injection of acetylcholine. The results also indicate that in many patients with vasospastic angina, nonspecific hypersensitivity to acetylcholine or ergonovine in a definite region of the coronary arteries generally plays an important role in the induction of coronary spasm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615827 TI - Coronary collaterals reduce the duration of exercise-induced ischemia by allowing a faster recovery. AB - The role of collaterals in influencing postischemic recovery after exercise testing has not been investigated previously. We studied 54 patients (mean age 59 +/- 6 years) with effort-induced angina and documented coronary disease who underwent exercise testing and thallium-201 myocardial scintigraphy. On angiography, 30 patients (group A) exhibited visible collaterals (grade 2 to 3, Cohen and Rentrop classification) perfusing the ischemic zone, whereas the other 24 (group B) did not. Patients with collaterals had more severe coronary artery disease (Gensini score 46.9 +/- 16 vs 28.6 +/- 18; p less than 0.001) and more severe impairment of coronary flow reserve (time and rate-pressure product to 1 mm ST segment depression 3.5 +/- 0.8 vs 4.8 +/- 0.6 minutes, p less than 0.01; 14,189 +/- 2451 vs 16,081 +/- 2215 beats/min x mm Hg, p less than 0.04, respectively). However, in these patients the ECG returned to baseline more rapidly after exercise (5.5 +/- 1.6 vs 11.7 +/- 3.3 minutes; p less than 0.001). Therefore, although collaterals do not apparently prevent or delay the development of exercise-induced ischemia, they can limit its duration by allowing a faster recovery. PMID- 1615828 TI - Effects of intracoronary dipyridamole infusion on regional myocardial blood flow and intrinsic thallium-201 washout in dogs with a critical coronary stenosis. AB - Intravenous dipyridamole (DP) infusion produces a significant endocardial-to epicardial flow gradient distal to a critical coronary stenosis, resulting in diminished regional thallium-201 (Tl-201) uptake and washout. Intravenous DP can also produce a significant decrease in arterial blood pressure and therefore in coronary perfusion pressure. We determined to further clarify the mechanism of this transmural coronary "steal" employing intracoronary DP administration, thereby avoiding systemic hypotension. In five of eight dogs with a critical left anterior descending (LAD) stenosis, intracoronary DP caused no significant fall in systemic arterial pressure, a rise in epicardial flow from 1.15 +/- 0.2 to 1.75 +/- 0.2 ml/min/gm, and a slight fall in subendocardial flow from 1.15 +/- 0.2 to 1.03 +/- 0.5 ml/min/gm. Intracoronary DP caused no prolongation of the intrinsic Tl-201 washout rate. In three dogs that developed systemic hypotension after intracoronary DP, endocardial flow fell from 1.14 to 0.63 ml/min/gm, the epicardial/endocardial flow ratio fell to 0.35, and Tl-201 washout became more prolonged. Thus intracoronary DP in the setting of a critical LAD stenosis caused minimal endocardial-to-epicardial steal and had no effect on the intrinsic Tl-201 washout rate unless it was accompanied by a fall in systemic arterial pressure. The magnitude of the transmural steal was substantially less than reported in our previous experiments utilizing intravenous DP infusion. This study provides a further insight into the mechanism of DP-induced subendocardial ischemia and suggests that systemic hemodynamic alterations play an important role in the effects of the vasodilator on myocardial blood flow and Tl-201 kinetics. PMID- 1615829 TI - Analysis of thallium-201 single-photon emission computed tomography after intravenous dipyridamole using different quantitative measures of coronary stenosis severity and receiver operator characteristic curves. AB - The presence of significant coronary artery disease in individual vessels was assessed using thallium-201 single-photon emission computed tomography (SPECT) after intravenous dipyridamole. Coronary angiograms were analyzed using quantitative computer-assisted techniques in 81 men patients. Eleven men with a less than 3% probability of coronary artery disease were used as a control population. Three definitions of a hemodynamically significant coronary stenosis were studied independently: (1) a greater than 50% luminal diameter narrowing; (2) an absolute cross-sectional area less than or equal to 2.0 mm2; or (3) a greater than or equal to 70% cross-sectional area obstruction. Myocardial perfusion after dipyridamole was analyzed using the quantitative (polar map) method in 213 regions from the group with known coronary anatomy and using 33 regions from the group with a low likelihood of disease. Receiver operating characteristic curves were used to define the best cut-off point for the discrimination between normal and abnormal perfusion. When related to each of the three quantitative angiographic criteria, the optimum balance between sensitivity and specificity occurred at a defect size of greater than or equal to 8% for the left anterior descending artery, greater than or equal to 4% for the circumflex artery, and greater than 0% for the right coronary artery. Using a luminal diameter narrowing of greater than 50% to define the presence of significant coronary artery disease, these corresponded to respective sensitivities and specificities of 0.82 and 0.76 for the left anterior descending artery, 0.71 and 0.71 for the circumflex artery, and 0.76 and 0.82 for the right coronary artery. Thus analysis of receiver operator characteristic curves provides a means to define abnormalities for the SPECT polar map program after dipyridamole stress. Different definitions of coronary stenosis significance as determined by quantitative angiography did not substantially alter the results of the thallium imaging data and thus suggest that these definitions are functionally similar. PMID- 1615830 TI - Relationship between exercise echocardiography and perfusion single-photon emission computed tomography in patients with single-vessel coronary artery disease. AB - The aim of this study was to assess the relative value of exercise echocardiography and perfusion single-photon emission computed tomography (SPECT) in identifying the presence and severity of coronary artery stenosis. Accordingly, 44 consecutive patients with stenosis in one vessel performed simultaneous postexercise echocardiography and perfusion SPECT (with either thallium-201 [n = 19] or 99m-Tc-methoxyisobutyl isonitrile [n = 25]) in conjunction with symptom-limited bicycle exercise testing. Positive test results were based on the presence of new or worsened exercise-induced wall motion abnormalities and transient perfusion defects, respectively. Moreover, an "ischemic" score index was derived for semiquantitative assessment of both echocardiography (with a 14-segment model of left ventricular wall on a 4-point scale) and SPECT (47-segment model on a 5-point scale). All patients underwent correlative coronary arteriography, assessed by digital caliper. Significant coronary artery disease (diameter stenosis greater than or equal to 50%) was present in 30 patients. There was a good overall concordance between the two tests in terms of result (79%); compared with patients with positive results of both tests, in the seven patients with positive SPECT and negative echocardiography the time of recording echocardiographic images was longer (p = 0.05). When analyzing patients according to the percent diameter stenosis (greater than 70%, 50% to 70%, and less than 50%) for both echocardiography and SPECT, the prevalence of an ischemic response was directly related to the severity of the coronary stenosis (p less than 0.001); moreover, a negative test result was highly predictive of a diameter coronary stenosis less than 70%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615831 TI - Ventricular tachycardia after infarction: sources of coronary blood flow to the infarct zone. AB - The purpose of this study was to determine the sources of coronary blood flow to infarct scars in patients with sustained ventricular tachycardia occurring late after myocardial infarction, which is necessary for transcoronary sclerosis or embolization. Angiograms of 32 consecutive patients (age 63 +/- 8 years, ejection fraction 0.30 +/- 0.10) were reviewed. Sources of blood flow to the infarct zone were identified as coming from a recanalized infarct-related artery, side branch, collateral, or coronary bypass graft. Eighty-four percent of patients in the study had an identifiable blood supply to the area of previous infarction. More than one source of blood flow to anterior infarct locations were observed more often than to inferior infarct locations (53% vs 17%, p = 0.03). Transcoronary mapping for possible chemical ablation should be technically feasible in the majority of patients with ventricular tachycardia. Infarct zone blood flow arises from any of several sources and varies somewhat depending on infarct location. PMID- 1615832 TI - Prognostic significance of programmed ventricular stimulation in patients surviving complicated acute myocardial infarction: a prospective study. AB - In survivors of complicated myocardial infarction, the inducibility of sustained ventricular tachycardia may help identify a subset that is at increased risk for subsequent sudden cardiac death or spontaneous sustained ventricular tachycardia. We performed prehospital discharge programmed ventricular stimulation in 86 survivors of acute myocardial infarction complicated by heart failure, angina pectoris, or nonsustained ventricular tachycardia. These patients also underwent cardiac catheterization with coronary angiography and 24-hour ambulatory ECG recording. Programmed ventricular stimulation induced sustained ventricular tachycardia in 19 patients (22%) and ventricular fibrillation in six (7%) and did not induce these arrhythmias in 61 patients (71%). During an average follow-up of 18 +/- 13 months, 11 patients had arrhythmic events (seven sudden death and four nonfatal spontaneous sustained ventricular tachycardia) and 10 patients had nonsudden cardiac death. The total cardiac mortality rate was 20%. Arrhythmic events occurred in 32% of the 19 patients with inducible sustained ventricular tachycardia compared with 7% of the remaining 67 patients (p less than 0.003). By multivariate analysis the occurrence of arrhythmic events was independently predicted by both inducible sustained ventricular tachycardia and Killip class III or IV heart failure. The risk of arrhythmic events was 4.4% in the absence of both variables versus 38.4% (p less than 0.001) when both variables were present. The total cardiac mortality rate was best predicted by low left ventricular ejection fraction (less than 30%). Thus programmed ventricular stimulation is useful in risk stratification of survivors of complicated acute myocardial infarction. The prognostic utility appears to be particularly high in patients with infarction complicated by Killip class III or IV heart failure. PMID- 1615833 TI - Multivessel and single-vessel coronary angioplasty: a comparative study. AB - To determine the efficacy of multivessel coronary angioplasty, 569 consecutive patients undergoing multivessel angioplasty were compared with 569 age- and sex matched control patients undergoing single-vessel angioplasty. Baseline variables were similar except for number of diseased vessels and greater left ventricular dysfunction in the multivessel group. Major in-hospital complication rates (death, 0% vs 0.5%; Q wave myocardial infarction, 0.5% vs 0.9%; emergency bypass surgery, 2.5% vs 3.2%) were similar for multivessel and single-vessel angioplasty. The 5-year actuarial survival rate was 93% for multivessel angioplasty and 92% for single-vessel angioplasty. Event-free survival was similar except that patients undergoing multivessel angioplasty had an 8% higher incidence of repeat coronary angioplasty in the first year of follow-up (p = 0.03). Multivessel coronary angioplasty can be performed with results comparable to those of single-vessel angioplasty with the exception of a higher incidence of repeat angioplasty. PMID- 1615834 TI - Biphasic versus sequential pulse defibrillation: a direct comparison in pigs. AB - It has recently been demonstrated that both biphasic and sequential pulse defibrillation shocks are superior to monophasic defibrillation shocks in animals and humans. There is little information directly comparing these two waveforms when pulse characteristics, subject, and total electrode surface area are kept constant. Pigs were randomized in a cross-over design for triplicate determinations of defibrillation threshold using biphasic and sequential pulse shocks and both large and small epicardial electrodes. Anesthetized pigs weighing 18 to 28 kg had sets of defibrillating electrodes (TX-7) with total surface areas of 13 cm2 (group 1, n = 16) and 26 cm2 (group 2, n = 16), respectively, attached to the heart. Leading edge delivered voltage, current, and energy were significantly lower with sequential pulse shocks than with biphasic shocks for both electrode sets (delivered energy means +/- standard error of the mean: 13.3 +/- 1.6 versus 22.4 +/- 3.0 joules, and 9.9 +/- 1.5 versus 14.2 +/- 1.6 joules, respectively). In addition, six of the pigs could not be defibrillated with 900 stored V using biphasic shocks, although all pigs were defibrillated with less than 800 stored V using sequential pulse defibrillation. We conclude that sequential pulse defibrillation using three defibrillating electrodes provides an important current delivery system not matched by biphasic shocks using two electrodes when subject, waveform characteristics, and total electrode surface area are kept constant. PMID- 1615835 TI - Who needs the apothecary system? PMID- 1615836 TI - Use of stationary automated blood pressure devices in pharmacies. PMID- 1615837 TI - Conducting at-home medication reviews. PMID- 1615838 TI - Fostering professional growth in young pharmacists. PMID- 1615839 TI - The 'little, round, white pill' problem. PMID- 1615840 TI - Leaflets reinforce counseling. PMID- 1615841 TI - Use sensitivity in providing drug literature. PMID- 1615842 TI - Xanax can lead to dependency. PMID- 1615843 TI - Use of ACE inhibitors in the treatment of cardiovascular disease. AB - ACE inhibitors have been available by prescription since the marketing of captopril in the early 1980s. Since that time, six additional ACE inhibitors have been marketed, four of which received approval from the Food and Drug Association in 1991. All but one of the new ACE inhibitors are carboxylic-acid compounds, and all of them maintain a pro-drug metabolic pathway. Initially, ACE inhibitors were approved only for the control of high blood pressure. More recently, captopril and enalapril have been approved for use in congestive heart failure. In 1988, ACE inhibitors were one of the recommended first-line therapies for mild-to moderate hypertension. Their use in patients with hypertension has steadily increased, most likely because of their minimal effect on coexistent cardiovascular risk factors. In CHF, ACE inhibitors are the only single drug class that has been shown to reduce mortality and hospitalizations due to the disease without concomitant administration of another drug. ACE inhibitors are clearly drugs that should be used early in the treatment of most patients with CHF. Differences between ACE inhibitors are often difficult to define. As information regarding the clinical utility of tissue ACE inhibition is unveiled, the ability to use a selected ACE inhibitor based on individual patient characteristics may increase. The future for ACE inhibition looks promising and the cumulative clinical value of ACE inhibition appears to be just beginning. PMID- 1615844 TI - Eyedrop comparison. PMID- 1615845 TI - 'No' to single-entry doctor's degree. PMID- 1615846 TI - Gemfibrozil-lovastatin therapy for primary hyperlipoproteinemias. AB - The specific aim of this retrospective, observational study was to assess safety and efficacy of long-term (21 months/patient), open-label, gemfibrozil-lovastatin treatment in 80 patients with primary mixed hyperlipidemia (68% of whom had atherosclerotic vascular disease). Because ideal lipid targets were not reached (low-density lipoprotein (LDL) cholesterol less than 130 mg/dl, high-density lipoprotein (HDL) cholesterol greater than 35 mg/dl, or total cholesterol/HDL cholesterol less than 4.5 mg/dl) with diet plus a single drug, gemfibrozil (1.2 g/day)-lovastatin (primarily 20 or 40 mg) treatment was given. Follow-up visits were scheduled with 2-drug therapy every 6 to 8 weeks, an average of 10.3 visits per patient, with 741 batteries of 6 liver function tests and 714 creatine phosphokinase levels measured. Only 1 of the 4,446 liver function tests (0.02%), a gamma glutamyl transferase, was greater than or equal to 3 times the upper normal limit. Of the 714 creatine phosphokinase levels, 9% were high; only 1 (0.1%) was greater than or equal to 3 times the upper normal limit. With 2-drug therapy, mean total cholesterol decreased 22% from 255 to 200 mg/dl, triglyceride levels decreased 35% from 236 to 154 mg/dl, LDL cholesterol decreased 26% from 176 to 131 mg/dl, and the total cholesterol/HDL cholesterol ratio decreased 24% from 7.1 to 5.4, all p less than or equal to 0.0001. Myositis, attributable to the drug combination and symptomatic enough to discontinue it, occurred in 3% of patients, and in 1% with concurrent high creatine phosphokinase (769 U/liter); no patients had rhabdomyolysis or myoglobinuria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615847 TI - Comparison of delay times to hospital presentation for physicians and nonphysicians with acute myocardial infarction. AB - To evaluate whether patients who recognize the symptoms of myocardial ischemia and have easy access to medical care have shortened time delays between onset of symptoms and hospital presentation, the total time interval between symptom onset and hospital arrival for 258 U.S. male physicians experiencing a first acute myocardial infarction (AMI) in the Physicians' Health Study (PHS) was compared with that of a comparable group of 240 men enrolled in the U.S. component of the Second International Study of Infarct Survival (ISIS-2), as well as with those of previously published series of patients with AMI. For patients presenting for medical care within 24 hours of symptom onset, the median time delay from onset of symptoms to presentation for medical care was 1.8 hours in the PHS, and 4.9 hours in the U.S. component of ISIS-2 (p less than 0.001). Furthermore, 56% of participants in the PHS presented for medical care within 2 hours and 72% within 4 hours of symptom onset compared with 20% (p less than 0.001) and 44% (p less than 0.001), respectively, for ISIS-2 participants. In previously published series, the average time to presentation was comparable to that in the ISIS-2 trial, with variation depending on country of origin and on local population density. The median time to medical presentation in any previous series was not shorter than that in the PHS. Thus, physicians in the PHS had significantly shorter time delays between onset of symptoms and presentation for medical care. This difference may help explain the far lower than expected cardiovascular mortality rates among physician participants in the PHS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615848 TI - Aggravation of arrhythmia by antiarrhythmic drugs, and the important role of underlying ischemia. PMID- 1615849 TI - Reduction of QT-interval imprecision and variance by measuring the JT interval. PMID- 1615850 TI - Stenting for elastic recoil during coronary angioplasty of the left main coronary artery. PMID- 1615851 TI - Aspiration thrombectomy for removal of coronary thrombus. PMID- 1615852 TI - Disparate serum lipid changes between normotensive and hypertensive women during the menstrual cycle. PMID- 1615853 TI - Atrial and ventricular approaches for radiofrequency catheter ablation of left sided accessory pathways. PMID- 1615854 TI - Doppler detection of valvular regurgitation after radiofrequency ablation of accessory connections. PMID- 1615855 TI - Safety of percutaneous transvenous balloon mitral commissurotomy in patients with mitral stenosis and thrombus in the left atrial appendage. PMID- 1615856 TI - The four subtypes of anomalous origin of the left main coronary artery from the right aortic sinus (or from the right coronary artery). PMID- 1615857 TI - Congenital hypoplasia of both right and left circumflex coronary arteries. PMID- 1615858 TI - Frequency of thromboembolic stroke in persons greater than or equal to 60 years of age with extracranial carotid arterial disease and/or mitral annular calcium. PMID- 1615859 TI - Echocardiographic frequency and severity of aortic regurgitation after ultrasonic aortic valve debridement for aortic stenosis in persons aged greater than 65 years. PMID- 1615861 TI - Intraventricular muscle band mimicking asymmetric ventricular septal hypertrophy and hypertrophic cardiomyopathy. PMID- 1615860 TI - Sinus node artery occlusion for treatment of chronic nonparoxysmal sinus tachycardia. PMID- 1615862 TI - Less money for doctors in the future? PMID- 1615863 TI - Noninvasive identification of severe coronary artery disease using exercise tomographic thallium-201 imaging. AB - The ability of exercise thallium-201 tomographic imaging to predict the presence of left main or 3-vessel coronary artery disease (CAD) was examined in 688 patients who underwent both exercise thallium-201 testing and coronary angiography. Significant differences existed for multiple variables between patients with (n = 196) and without (n = 492) severe left main or 3-vessel CAD. Logistic regression analysis identified 4 variables as independently predictive of left main or 3-vessel CAD. These variables were the magnitude of ST-segment depression with exercise, the number of visually abnormal short-axis thallium-201 segments, the presence or absence of diabetes mellitus, and the change in systolic blood pressure with exercise. Using these variables, patients were classified by nomograms into low-, intermediate- and high-probability groups. Patients at high probability (n = 205) had a 52% prevalence of 3-vessel or left main CAD, whereas those at low probability (n = 170) had only a 12% prevalence. Only 53 patients (29%) with 3-vessel or left main CAD had perfusion abnormalities in all 3 coronary territories. Clinical and exercise parameters provide important independent information in the identification of left main or 3-vessel CAD by exercise thallium-201 tomographic imaging, because thallium scintigraphy alone is suggestive of extensive CAD in few patients. PMID- 1615864 TI - Effect of thrombolytic therapy on the predictive value of signal-averaged electrocardiography after acute myocardial infarction. AB - Standard time domain variables from signal-averaged electrocardiography were examined in a population of 331 survivors of acute myocardial infarction. Of these subjects, 130 received early (less than 24 hours) thrombolytic therapy. During a follow-up of greater than or equal to 10 months, there were 17 arrhythmic events (8.5%) (sudden death or sustained symptomatic ventricular tachycardia) in the group without thrombolysis and 8 (6.2%) in those with thrombolysis. Statistically, highly significant differences between the signal averaged electrocardiographic variables of patients with and without arrhythmic events were found in the group without thrombolysis, whereas only root-mean square voltage of the terminal 40 ms of the signal-averaged QRS complex was statistically associated with outcome (the differences in the other 2 indexes being not significant) in patients with thrombolysis. When using 2 previously published categoric criteria for the diagnosis of abnormal signal-averaged electrocardiography, the performance of these criteria in predicting arrhythmic events was substantially better in the group without thrombolysis than in those with thrombolysis (positive predictive accuracy greater than 3 times lower). Retrospectively adjusted receiver-operator characteristics showed that for a sensitivity of 30%, the maximum achievable positive predictive accuracy of signal averaged electrocardiography for arrhythmic events was 100% in the group without thrombolysis, but only 27% in those with thrombolysis. It is concluded that standard signal-averaged electrocardiography after acute myocardial infarction is less informative in patients who receive thrombolytic treatment. PMID- 1615865 TI - Six-year survival after coronary thrombolysis and early revascularization for acute myocardial infarction. AB - Six-year follow-up was conducted in a consecutive series of 192 patients receiving thrombolytic therapy for acute myocardial infarction (AMI) with ST segment elevation. Cardiac catheterization was performed within a day, and patients with an open infarct artery routinely had early revascularization: 99 (67%) underwent coronary bypass surgery and 18 (12%) coronary angioplasty. With this treatment strategy, 6-year cardiac mortality was 14.5%, 6% (12 patients) in hospital and 9% (16 patients) for survivors of hospitalization. Multivariate analysis showed that predictors of cardiac death among survivors of hospitalization were a closed infarct artery at catheterization (p less than 0.01), diabetes (p less than 0.01) and anterior myocardial infarction (p = 0.01). A subset of 146 patients underwent radionuclide angiography before hospital discharge; for them, predictors of mortality were a closed infarct artery at catheterization (p less than 0.01), anterior wall AMI (p = 0.02), and Killip class III to IV on admission (p less than 0.06). Left ventricular ejection fraction was not a significant predictor of mortality for this subset of patients. PMID- 1615866 TI - Value of negative predischarge exercise testing in identifying patients at low risk after acute myocardial infarction treated by systemic thrombolysis. AB - Although thrombolytic therapy reduces mortality in patients with acute myocardial infarction (AMI), it is associated with a greater incidence of successive coronary events, and there is still no ideal diagnostic and therapeutic strategy for such patients. The present study verifies the value of negative predischarge exercise testing in identifying low-risk patients treated with thrombolysis after AMI. One hundred fifty-seven consecutive patients with an uncomplicated clinical course underwent maximal or symptom-limited exercise testing (Bruce treadmill protocol) within 15 days of AMI in the absence of therapy. The location of the AMI was anterior in 51 patients, inferior in 85 and non-Q-wave in 21. All of the patients were followed for 6 months. Death and nonfatal reinfarction were considered as major coronary events, and the recurrence of angina as a minor event. Exercise test results were negative in 105 patients (group 1) and positive for angina or ST depression greater than or equal to 0.1 mV in 52 (group 2). No deaths occurred during follow-up; there were 3 reinfarctions (3%) and 7 cases (7%) of postinfarction angina in group 1, and 2 reinfarctions (4%) and 21 cases (40%) of postinfarction angina in group 2. By the end of follow-up, 90% of the patients with negative exercise test results were event-free (97% in the case of major events). These results show that thrombolytic therapy does not affect the value of negative postinfarction exercise testing in identifying low-risk patients. PMID- 1615867 TI - Magnetic resonance imaging during dobutamine stress in coronary artery disease. AB - Cine magnetic resonance imaging (MRI) provides a tomographic method of assessing regional ventricular function in any desired plane. It has not been possible to obtain adequate images during dynamic exercise, and this has limited its value in patients with coronary artery disease (CAD). Therefore, an infusion of dobutamine was used to study 25 patients with exertional chest pain and abnormal exercise electrocardiograms. Areas of abnormal wall motion were compared with areas of abnormal myocardial perfusion imaged by dobutamine thallium emission tomography and with coronary arteriography. Twenty-two patients had significant CAD. Twenty one (96%) of these patients had reversible myocardial ischemia shown by dobutamine thallium tomography, and 20 (91%) had reversible wall motion abnormalities shown by dobutamine MRI. Comparison of abnormal segments of perfusion and wall motion showed 96% agreement at rest, 90% agreement during stress, and 91% agreement for the assessment of functional reversibility. The normalized magnetic resonance signal intensity of the ischemic segments showed a small but significant reduction when compared with that of normal segments (-67 units [9.2%]; p less than 0.05). Dobutamine infusion was well-tolerated, despite causing chest discomfort in 24 patients (96%). Nine patients (36%) developed a minor dysrhythmia that was usually ventricular premature complexes, but this did not limit infusion, and other side effects were mild. The short plasma half-life of dobutamine makes it ideal as a stress agent for imaging techniques (such as MRI), and these results suggest that it is more effective in the provocation of wall motion abnormalities than is dipyridamole in patients with CAD. PMID- 1615868 TI - Enhanced sensitivity for detection of coronary artery disease by addition of atropine to dobutamine stress echocardiography. AB - Patients undergoing dobutamine stress echocardiography often take beta antagonists which limit heart rate response and sensitivity in the test for detection of coronary artery disease. The aim of this study was to assess the effect of the addition of atropine to dobutamine stress echocardiography on clinical, electrocardiographic and echocardiographic outcomes. Dobutamine stress echocardiography was performed starting at and increasing every 3 minutes with 10 micrograms/kg/min to a maximum of 40 micrograms/kg/min (stage 4), which was continued for 6 minutes. In patients not achieving 85% predicted maximal exercise heart rate and in whom the test was not judged positive on echocardiographic or electrocardiographic criteria, atropine (0.25 mg intravenously, repeated up to a maximum of 1 mg if necessary) was added and dobutamine continued for up to a further 5 minutes, or until an adequate heart rate was achieved or the test was stopped because of chest pain or electrocardiographic changes. Of 80 consecutive patients undergoing dobutamine stress echocardiography within 2 weeks of coronary angiography, 49 required atropine (group A) and 31 required only dobutamine (group B). After dobutamine alone, heart rate (mean +/- SD) was higher in group B than in group A: 129 +/- 20 vs 90 +/- 18 beats/min, p less than 0.0001; but after the addition of atropine, heart rate in group A increased to 120 +/- 20 beats/min. Overall sensitivity for the detection of coronary disease was 70%, 95% confidence interval (CI) 55 to 83%; after the addition of atropine, sensitivity for group A was 65%, 95% CI 45 to 81%; in group B, sensitivity was 81%, 95% CI 54 to 96%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615869 TI - Initial management and long-term clinical outcome of restenosis after initially successful percutaneous transluminal coronary angioplasty. AB - Restenosis remains a critical limitation after percutaneous transluminal coronary angioplasty (PTCA). The clinical experience with restenosis was reviewed in 1,490 patients who had restenosis of at least 1 site within 1 year of their PTCA. The source of data was the clinical database at Emory University. Patients who had previous coronary bypass surgery or PTCA and patients who underwent PTCA in the setting of acute myocardial infarction were excluded. When restenosis was angiographically documented, 363 were treated medically, 1,051 with repeat PTCA, and 76 with coronary bypass surgery. In the repeat PTCA group there were 778 patients who originally had 1-vessel disease and 273 with multiple vessel disease. Re-dilatation of restenotic sites was performed in 95%. Angiographic success of all lesions dilated was achieved in 99%. Coronary bypass surgery was required in 2.5% of patients with restenosis first treated with repeat PTCA. One patient with multiple vessel disease died. Coronary bypass surgery was performed in fewer patients aged greater than or equal to 65 years, but more patients with multiple vessel disease. Two (2.6%) of the coronary bypass surgery patients had Q wave myocardial infarction and there were no deaths. In the PTCA group, 5-year actuarial survival was 95%, and cardiac survival 96%. Freedom from cardiac events or further revascularization procedures was 51% at 5 years. Patients treated with PTCA and medically treated patients had similar cardiac survival rates. The most important correlates of cardiac survival were age and the presence of diabetes mellitus. At 5 years, cardiac survival without diabetes was 97 and 83% with diabetes (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615870 TI - Usefulness of a postoperative exercise test for predicting cardiac events after coronary artery bypass grafting. AB - The predictive value of a postoperative exercise test in terms of cardiac events after coronary artery bypass grafting (CABG) was prospectively studied in 231 consecutive patients. During a 5-year follow-up there were 28 cardiac events (12%), of which 15 were cardiac deaths (13 sudden), and 13 were nonfatal myocardial infarctions. There was no difference in the rate of graft patency between groups with and without cardiac events, but ejection fraction was lower in patients with than without events (51 +/- 16% vs 58 +/- 10%; p less than 0.05). Duration of the exercise test was shorter, and maximal work load was lower in patients with cardiac events (p less than 0.05 for both). The prevalence of greater than or equal to 1 mm ST-segment depression was 22% (symptomatic in 25%, and silent in 75%) and did not differ between groups with and without cardiac events. After adjustment for prognostic variables using the proportional hazards method, diuretic treatment (p = 0.007) and a low postoperative ejection fraction (p = 0.04) remained significant for predicting the risk of cardiac events within 5 years of CABG, but exercise duration and work load did not have any significant predictive value. Thus, the predictive value of a postoperative exercise test is limited, and signs of impaired left ventricular function are of greater significance for the 5-year prognosis after CABG than are those of myocardial ischemia. PMID- 1615871 TI - Comparison of patient-reported outcomes after elective coronary artery bypass grafting in patients aged greater than or equal to and less than 65 years. AB - Older patients represent a growing proportion of patients undergoing coronary artery bypass grafting (CABG). Although functional benefits after CABG have been demonstrated, most assessments of outcomes have involved patients aged less than 65 years. Therefore, little is known concerning the impact of CABG on older patients compared with that on younger ones. A number of postsurgical (6 months) health-related quality-of-life outcomes (e.g., symptoms, cardiac functional class, instrumental activities of daily living, and emotional and social functioning) reported by patients aged less than 65 (n = 169) and greater than or equal to 65 (n = 99) years who underwent elective CABG at 4 major teaching hospitals in Massachusetts and California were compared. The proportion of patients reporting cardiac-related symptoms after surgery did not vary by age, and quality-of-life outcome scores of younger and older patients did not differ even after adjustment for clinical and demographic characteristics. The exception to this was mental health status, an outcome for which older patients reported better functioning than did younger ones. On average, patients in the 2 age groups reported equivalent improvement over preadmission status in instrumental activities of daily living, and emotional and social functioning. The independent relation of clinical and sociodemographic factors to quality-of-life outcomes was also investigated. Patients who functioned better before admission, those with less severe co-morbid disease, and married patients reported better functioning after discharge. In general, older patients who underwent elective CABG reported functional benefits similar to those reported by younger ones, and the factors associated with better functioning did not vary by age group. PMID- 1615872 TI - Increased onset of sudden cardiac death in the first three hours after awakening. AB - A circadian variation of sudden cardiac death has been documented, but its relation to individual time of awakening and possible triggering events has not been studied in the general population. By monitoring of mortality records in 4 cities and towns in Massachusetts, 148 potential cases of sudden cardiac death were identified. In 94 cases, the informants listed on the death certificates were contacted, the diagnosis of sudden cardiac death was established, and a telephone interview was completed within a mean of 19 days (range 8 to 28) after the death. The time of day of all 94 cases of sudden cardiac death (mean age 61 +/- 9 years, 74% men) demonstrated a circadian variation (p less than 0.05) with a peak from 9:00 A.M. to 12:00 noon. An analysis of time of death adjusted for individual wake-times of the decedents demonstrated an increased onset of sudden cardiac death during the initial 3-hour interval after awakening with a relative risk of 2.6 (95% confidence interval 1.6, 4.2) compared with other times of the day. The increased risk of sudden cardiac death soon after awakening suggests specific triggering factors or mechanisms that are particularly likely to occur during this time. The narrowing of the time interval during which the risk of sudden cardiac death is increased should facilitate the study of possible pathogenetic mechanisms and triggering factors of the disease and may aid in the design of more effective preventive strategies. PMID- 1615873 TI - Effectiveness of loading oral flecainide for converting recent-onset atrial fibrillation to sinus rhythm in patients without organic heart disease or with only systemic hypertension. AB - Sixty-two patients with recent-onset (less than or equal to 1 week) atrial fibrillation (New York Heart Association functional class 1 and 2) were randomized in a single-blind study to 1 of the following treatment groups: (1) flecainide (300 mg) as a single oral loading dose; or (2) amiodarone (5 mg/kg) as an intravenous bolus, followed by 1.8 g/day; or (3) placebo for the first 8 hours. Twenty-four-hour Holter recording was performed, and conversion to sinus rhythm at 3, 8, 12 and 24 hours was considered as the criterion of efficacy. Conversion to sinus rhythm was achieved within 8 hours (placebo-controlled period) in 20 of 22 patients (91%) treated with flecainide, 7 of 19 (37%) treated with amiodarone (p less than 0.001 vs flecainide), and 10 of 21 (48%) treated with placebo (p less than 0.01 vs flecainide). Resumption of sinus rhythm within 24 hours occurred in 21 of 22 patients (95%) with flecainide and in 17 of 19 (89%) with amiodarone (p = not significant). Mean conversion times were shorter for flecainide (190 +/- 147 minutes) than for amiodarone (705 +/- 418; p less than 0.001). No major side effects occurred. At Holter monitoring, a pause of 9.3 seconds was observed in 1 asymptomatic patient treated with flecainide. Phases of atrial flutter with a ventricular rate less than or equal to 150 beats/min were detected before sinus conversion in 1 patient receiving placebo and in 2 receiving flecainide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615874 TI - Electrocardiographic changes and arrhythmias after cancer therapy in children and young adults. AB - Transient electrocardiographic changes and arrhythmias are known to be acute manifestations of cardiotoxicity secondary to cancer therapy with anthracyclines or cardiac irradiation. However, despite the known risk of late cardiac dysfunction in survivors of childhood cancer therapy, the risk of clinically important electrocardiographic abnormalities and arrhythmias after treatment is unknown. Standard 12-lead and 24-hour ambulatory electrocardiograms were recorded in 73 patients who received anthracyclines alone, 24 who received cardiac irradiation alone, and 27 who received both anthracyclines and cardiac irradiation. The mean age of the patients was 15 years. Mean cumulative anthracycline dose was 282 mg/m2 in patients who received anthracyclines alone and 244 mg/m2 in patients who received both anthracyclines and cardiac irradiation. Analysis of the 12-lead and 24-hour electrocardiograms demonstrated increased frequency of QTc prolongation, supraventricular premature complexes, supraventricular tachycardia, ventricular premature complexes, couplets and ventricular tachycardia (all p less than 0.001) when compared with an age-matched healthy population. Most patients had abnormalities limited to single supraventricular or ventricular premature complexes; however, potentially serious ventricular ectopy, including ventricular pairs and ventricular tachycardia, were noted in patients with cumulative doses greater than 200 mg/m2. Electrocardiographic abnormalities and arrhythmias are not limited to the acute phase of treatment with anthracyclines and cardiac irradiation. Survivors of childhood malignancy who received anthracyclines or cardiac irradiation, or both, probably should undergo ambulatory electrocardiographic monitoring as part of their follow-up to detect potentially life-threatening arrhythmias. PMID- 1615875 TI - Silent myocardial ischemia in men with systemic hypertension and without clinical evidence of coronary artery disease. AB - The prevalence, characteristics and circadian pattern of silent myocardial ischemia, and its association with ventricular arrhythmias was studied in hypertensive men aged 35 to 70 years (mean 61) without clinical cardiac disease. Participants were withdrawn from diuretic treatment and received 1 month of oral electrolyte repletion with 40 mmol of potassium chloride, and 400 mg of magnesium oxide daily. Twenty-four-hour Holter monitoring was then performed. Episodes of silent myocardial ischemia occurred in 50 of 186 men (27%) and lasted from 2 to 289 minutes (mean 30 and median 18). Statistical analysis comparing the interval from midnight to 6 A.M. with each of the other three 6-hour time intervals revealed that participants were less likely to have silent myocardial ischemia in this period (p less than 0.01 for each comparison) than at other times of the day. There was little difference in the proportion of men with a frequent or complex ventricular arrhythmia during the entire day or within 1 hour of the silent myocardial ischemic episode (or during a comparable time period) comparing those with to those without silent myocardial ischemia. These findings indicate that silent myocardial ischemia occurs in approximately 25% of an older population of hypertensive men without history of symptomatic cardiac disease. The circadian pattern of frequency of silent ischemic events in men free of clinical cardiac disease is similar to that reported for patients with cardiac disease and coincides with that reported for sudden death. There was no significant association between silent myocardial ischemia and ventricular arrhythmias. PMID- 1615876 TI - Effects of combined hydrochlorothiazide and amiloride versus single drug on changes in salt taste and intake. AB - Hydrochlorothiazide stimulates salt intake without altering salivary or gustatory function. Amiloride reportedly reduces salivary sodium levels and salt taste. It was hypothesized that these unintended drug actions would be attenuated by concurrent use of these 2 diuretics. Normotensive adults (n = 23) were administered placebo for 2 weeks, active combination drug Moduretic for 4 weeks, and placebo again for 2 weeks in a double-blind protocol. Salivary flow, gustatory function and sodium intake were monitored at the end of each period, together with selected physiologic measures (i.e., plasma aldosterone, plasma renin activity, body composition, blood pressure and heart rate). No significant changes were observed for salivary flow, salt taste or sodium intake. These findings indicate that amiloride and hydrochlorothiazide used in combination can reduce drug effects that may compromise the efficacy of either drug when used alone. PMID- 1615877 TI - Improvement of automated electrocardiographic diagnosis by combination of computer interpretations of the electrocardiogram and vectorcardiogram. AB - In the international project "Common Standards for Quantitative Electrocardiography" (CSE), diagnostic results of different computer programs for the interpretation of the electrocardiogram (ECG) and of the vectorcardiogram (VCG) were combined, and it was shown that the "combined program" performs better than each program separately. Because the program MEANS (Modular ECG Analysis System) comprises 2 different classification programs--one for the ECG, the other for the VCG--this allowed investigation of whether the combined interpretations would yield a better diagnostic result than either one separately. This approach requires that a VCG always be recorded in addition to the ECG. To circumvent this complication, the VCG was reconstructed from the simultaneously recorded ECG leads. This reconstructed VCG was then interpreted by the VCG classification program, whereupon the diagnostic interpretations of the ECG and the reconstructed VCG were combined. For the validation, the CSE database of documented ECGs and VCGs (n = 1,220) was used. The combination of the ECG and VCG interpretations yielded a better diagnostic result than each interpretation program separately (total accuracy 74.2% (ECG + VCG) vs 69.8% (ECG) and 70.2% (VCG), p less than 0.001 in both cases). The results for the reconstructed VCG (total accuracy 70.5%) are comparable to those for the ECG and the VCG (p greater than 0.10 in both cases). The performance of the combined interpretations of ECG and reconstructed VCG (total accuracy 73.6%) is approximately the same as that of the combined ECG and VCG (p greater than 0.10). Thus, the performance of an ECG computer program can be improved by incorporating both ECG and VCG classificatory knowledge, using only the ECG itself. PMID- 1615878 TI - Effect of low-calorie diets on the sympathetic nervous system, body weight, and plasma insulin in overweight hypertension. AB - When weight reduction was found to decrease blood pressure in the overweight hypertensive patient, it was hailed as the causative factor. A growing number of recent studies indicate that this association may be secondary to a correlation between diet-associated metabolic change and the sympathetic nervous system. A select group such as overweight hypertensive patients may have a genetic predisposition for such a correlation. In overweight hypertensive patients, low calorie diet and especially very-low-calorie diet, correlate with improved glucose metabolism, a decrease in plasma insulin concentration, and altered norepinephrine concentrations and thus sympathetic nervous system activity. Several of these studies also show a lack of effect of salt intake on blood pressure. Thus, it seems that metabolic changes caused by the decrease in caloric intake are responsible for the decrease in blood pressure. These must be investigated to understand the effect of the different diets on blood pressure. Very low-calorie diets were found very useful in breaking the vicious circle of severe nonresponsive hypertension to medication. PMID- 1615879 TI - Insulin sensitivity during very-low-calorie diets assessed by minimal modeling. AB - The time course of plasma glucose, insulin, and C-peptide after intravenous glucose (300 mg/kg body wt) injection was analyzed with minimal model approach in nine normal females and seven obese females. Glucose tolerance, estimated by glucose assimilation coefficient (KG), was positively correlated with glucose effectiveness (SG), but not correlated with peripheral insulin sensitivity (SI) in obese females as well as normal females. These factors were estimated before and after weight loss with 1.8-MJ (420-kcal) very-low-calorie diets (VLCDs) or with 2.5-3.3-MJ (600-800-kcal) low-calorie diets in two obese subjects. KG and glucose effectiveness decreased after acute weight loss with VLCD, although insulin sensitivity increased. Weight loss with low calorie diets resulted in improvement of KG and glucose effectiveness. These results suggest that a significant amount of glucose is taken up through insulin-independent mechanisms during the intravenous glucose tolerance test (ivGTT) in these subjects. This insulin-independent glucose uptake may be an important determinant of the fate of glucose in obese females as well as normal females. PMID- 1615880 TI - Effect of very-low-calorie diets with weight loss on obstructive sleep apnea. AB - To determine the effect of very-low-calorie diets (VLCDs) with weight loss on obstructive sleep apnea (OSA), we studied eight obese subjects with OSA, five males and three females. Subjects consumed a VLCD of 1760 kJ (420 kcal) (67% protein, 4% fat, 29% carbohydrate) or 3350 kJ (800 cal) (20% protein, 30% fat, 50% carbohydrate) with 100% of the recommended daily allowance of vitamins and minerals. Mean (+/- SD) values of weight and respiration before and after weight loss were, for weight, 153 +/- 37 and 132 +/- 29 kg (P less than 0.05); for BMI (kg/m2), 54 +/- 13 and 46 +/- 10 (P less than 0.05); for desaturations/h sleep, 106 +/- 50 and 52 +/- 45 (P less than 0.05); for apneas + hypopneas/h sleep, 90 +/- 32 and 62 +/- 49; for Pco2, 48 +/- 10 and 42 +/- 4 torr (P less than 0.05). Desaturation episodes/h and apnea + hypopneas/h improved in six patients. The most obese subject (female, BMI 81) who lost the most weight (47 kg) did not improve, nor did the subject who lost the least weight, 7 kg. The number of movements + arousals from sleep decreased in all patients (P less than 0.05). We conclude that VLCD with weight loss can produce improvement in OSA; subjects who lose a small amount of weight or subjects who are extraordinarily obese before and after weight loss may not improve. PMID- 1615881 TI - Psychological aspects of obesity and very-low-calorie diets. AB - This paper selectively reviews available evidence concerning psychological characteristics associated with obesity, psychological changes accompanying very low-calorie diets (VLCDs), and the influence of certain psychological factors on response to VLCD treatment. The obese population as a whole does not show an elevated incidence of psychopathology. Treatment-seeking obese do show more psychiatric disturbance, at a level comparable to other medical/surgical patients. There appear to be no global personality traits or profiles that are associated with obesity. However, obese people differ from non-obese groups on psychological and behavioral variables related to weight and eating and more frequently display perceptual and emotional body image anomalies. Binge eating appears rather common among obese groups. VLCDs have generally neutral to positive effects on hunger, depression, and anxiety. New data on body image suggest that VLCDs are associated with post-treatment underestimation of body size. Finally, recent data on possible psychological and behavioral correlates of VLCDs outcome are presented. PMID- 1615882 TI - Exercise during and after very-low-calorie dieting. AB - Neither diet nor exercise are effective as single modes of intervention in the treatment of obesity. Although it is logical that they be combined in the context of multidisciplinary treatment, restrictions in calorie or protein intakes while dieting may impair short-term or long-term function. The limited evidence available indicates that properly constituted very-low-calorie diets can effectively preserve physical function across major weight loss, but long-term preservation of this weight loss is strongly influenced by postdiet exercise habits. In summary, counseling on and initiation of safe and effective exercise practices during dietary treatment of obesity are appropriate, but the ultimate goal should be to direct the patient towards lifelong exercise behaviors that will contribute to sustained weight maintenance. PMID- 1615883 TI - Drug therapy after very-low-calorie diets. AB - Very-low-calorie diets (VLCDs) are effective at reducing weight, even in patients who have often failed with conventional diets. Maintaining weight lost by means of a VLCD remains a clinical challenge. Attempts to prevent weight regain by dietary reeducation or by more formal behavior-modification techniques are not easily applicable to large numbers of patients and are not always successful; the use of drugs to maintain and improve upon initial VLCD success could be of real clinical value. Pharmacological treatment of obesity has evolved in recent years with the development and licensing of potent serotonin agonists, such as dexfenfluramine (dF), acting as nonstimulant anorectic agents. Thermogenic drugs are not yet as advanced in clinical development and evaluation but offer the prospect of increasing energy output in the reduced obese patient. Drugs used to treat obesity need to be effective, to be safe, not to exhibit drug tolerance, and ideally, to be shown to reduce morbidity or mortality from obesity, particularly because treatment will need to be prolonged. Such requirements are not unique for treating obesity, they are similar for drugs used to treat other metabolic diseases such as hypercholesterolemia or diabetes. VLCD followed by dF has been shown to be effective. A double-blind trial randomized 45 patients who had successfully completed 8 wk of treatment on the Cambridge diet to either placebo or dF 15 mg twice daily for 26 wk. Patients continued on a diet giving 60 75% of daily energy needs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615884 TI - Combination of very-low-calorie diet and behavior modification in the treatment of obesity. AB - Very-low-calorie diets (VLCDs) cause rapid weight loss. However, weight regain is rapid upon discontinuing the VLCD unless lifestyle is altered. The addition of a behavioral-modification (BMOD) program improves the long-term outcome. The major components of a BMOD program to alter lifestyle are education about nutrition and eating habits with alteration of amount and patterns of eating, institution of an aerobic activity program designed to increase energy expenditure, training in self-awareness and assertiveness, and training in coping techniques for long-term alteration of lifestyle. By retrospective chart review, we evaluated two VLCD programs at the same institution. One program gave 12 wk of BMOD before a 12-wk course of VLCD (Program 1), then scheduled individual visits regularly thereafter. The other program used simultaneous VLCD and BMOD in a 26-wk treatment course (Program 2), consisting of 2 wk of stabilization on 5020 kJ/d (1200 kcal/d), 12 wk of VLCD, and 12 wk of transition to a low-calorie solid food diet. Follow-up was obtained at 1 y in both groups. Maximum weight loss was similar, but subjects in Program 2 regained about one-third of the lost weight versus approximately 10% in Program 2. A third program of preceding BMOD followed by a low-calorie diet (Program 3) gave similar weight maintenance at 1 y as Program 1. Prospective studies are needed to determine if BMOD simultaneously with or preceding VLCD promotes better long-term weight maintenance. These data confirm the benefits of long-term follow-up for maintaining weight loss. PMID- 1615885 TI - Relationship of dieting history to resting metabolic rate, body composition, eating behavior, and subsequent weight loss. AB - This study examined the relationship of dieting history to resting metabolic rate, body composition, and subsequent weight loss in 50 obese women. A preliminary study showed that the women were able to report with satisfactory reliability the number of diets in which they had engaged (mean = 4.9 +/- 0.5), as well as the total weight loss resulting from these diets (mean = 55.9 +/- 6.0 kg). We found no evidence that weight cycling, as measured by either of these variables, was associated at baseline with a reduced resting metabolic rate or an increased percentage of body fat. Nor did we find that weight cycling was associated with smaller weight losses in a prospective trial in which subjects were treated by very-low-calorie diet and behavior therapy. The clinical implications of these findings are discussed, as are the methodological problems encountered in conducting research on this topic. PMID- 1615886 TI - Effects of weight cycling on body composition. AB - It is frequently claimed that weight cycling, or "yo-yo" dieting, causes an inappropriate and permanent loss of lean body mass (LBM). Data are presented from a rural African population that undergoes profound weight cycling caused by an annual hungry season. No detrimental effect on LBM was observed. Data are also presented from an 18-wk prospective study of moderately obese British women who underwent three cycles of VLCD-induced weight loss and subsequent relapse. The proportion of weight lost as LBM was no greater than predicted. A review of the published results from experimental weight cycling in small animals also shows a high level of consensus that cycling does not significantly alter body composition. We conclude that, although weight cycling may affect growth of young animals, metabolic efficiency, and health, these effects are not mediated through permanent alterations in body composition. PMID- 1615887 TI - Factors influencing body composition during very-low-calorie diets. AB - Apparent body composition changes with weight loss on very-low-calorie diet (VLCD) can depend on the method of fat-free mass estimation. In this report the implications of differences in measurement by direct versus indirect methods are examined. The nitrogen sparing and protein economy associated with ketosis is relevant and results of clinical trials with diets of varying composition are presented. The analytical findings of a multicenter, multimethod long-term VLCD study illustrate protein and metabolic conservation during VLCD. Protein losses, by total body nitrogen, over 10 wk dieting, independent of body mass index, were 4.75% of weight lost, as conservatively expected from obesity tissue reduction with no degradation of total energy expenditure. The implications of utilization of glycogen (water and potassium release) in interpretation of diet success and of body compositional change is evaluated. Evidence is presented that ultimate compositional changes with weight change may be individually specific and that body composition may be predicted from weight considerations alone. PMID- 1615888 TI - Factors determining energy expenditure during very-low-calorie diets. AB - There is an important variability in short- and long-term weight loss success among obese subjects, regardless of the strategy used. It is still unclear whether this variability is a therapy-specific or a patient-specific problem. Changes in energy expenditure are probably a key factor in the phenomena of weight loss or weight regain. Factors influencing resting metabolic rate (RMR) and diet-induced thermogenesis (DIT) in obese patients are considered: age, fat mass, fat-free mass (FFM), sex and thyroid hormones are all related to the components of energy expenditure. Fat distribution estimates [expressed by waist to-hip ratio (WHR)] seem to be related to DIT rather than to RMR. Short- and long term effects of very-low-calorie diets (VLCDs) on RMR and DIT were investigated. Short-term weight loss by VLCD induced a significant (P less than 0.001) decrease of FFM with a concomitant decline of RMR values. A nonsignificant decreasing trend exists for thermogenesis. No further decrease of FFM was found after long term weight loss without differences in RMR/FFM or thermogenesis. Changes in FFM are known to be the major component of changes in RMR, but other factors may be involved. Also some other factors may account for the possible changes in diet induced thermogenesis during VLCD. Candidates for this include total fat mass, FFM, sex hormones, insulin concentrations, and fat distribution, of which insulin concentrations seem to determine RMR changes to an important extent. Fat distribution patterns per se or changes in WHR seem to account consistently (P less than or equal to 0.05) for changes in DIT during VLCD. PMID- 1615889 TI - Liver and gallbladder disease before and after very-low-calorie diets. AB - Hepatobiliary characteristics of untreated obese patients and those of patients reducing weight through very-low-calorie diets (VLCDs) are reviewed. In untreated obesity, hepatobiliary abnormalities are prevalent. Fatty change is common and may be related to insulin resistance. Moreover, portal inflammation and fibrosis are prevalent findings, also in the absence of alcohol abuse. The liver plays a key role in the hyperinsulinism and hyperlipidemia, and hepatic drug metabolism is influenced by enhanced glucuronidation and sulphatation. Predisposition to gallstone formation can be ascribed to increased biliary cholesterol secretion in concert with changed nucleating factors and altered gallbladder motility. Weight loss by VLCD reduces fatty change but may induce slight portal inflammation and fibrosis. Insulin resistance and pharmacokinetic abnormalities regress. During VLCD the risk of gallstone formation is markedly increased. The deleterious effects described of a rapid weight loss should draw some attention to the liver and biliary tract during VLCD treatment. PMID- 1615890 TI - The role of very-low-calorie diets in obesity. AB - The popularity of very-low-calorie diets (VLCDs) is enormous, but questions persist about their safety and their long-term efficacy. This article addresses the following questions: who should be placed on a VLCD? when should a patient go on a VLCD? how much should an individual lose? where should a VLCD program be carried out and by whom? It stresses the importance of evaluating VLCD programs by their long-term goals and long-term results. Also, a few of the unanswered questions in VLCD treatment are addressed. Finally, worrisome financial-ethical questions of the business of VLCDs is discussed. PMID- 1615891 TI - Weight loss and 2-y follow-up for 80 morbidly obese patients treated with intensive very-low-calorie diet and an education program. AB - Eighty morbidly obese individuals consecutively enrolled in a comprehensive very low-calorie diet (VLCD) program were evaluated. Patients' mean initial body mass index was 45.5 kg/m2 and they lost 35.3 kg in 26 wk. Serum total cholesterol, low density-lipoprotein cholesterol, and triglycerides decreased by 15.0%, 17.0%, and 14%, respectively. Systolic and diastolic blood pressure decreased by 8.7% and 10.0%, respectively. The 46 individuals completing 2-y follow-up were maintaining 48.0 +/- 7.6% (means +/- SE) of their weight loss. Morbidly obese persons lost substantial amounts of weight using a comprehensive VLCD program, reduced risk factors associated with obesity, and had encouraging long-term results, with 48% of weight loss maintained at 2 y of follow-up. PMID- 1615892 TI - Weight loss by very-low-calorie diets: effects on substrate oxidation, energy expenditure, and insulin sensitivity in obese subjects. AB - Weight reduction improves glucose utilization, but it is not known whether this occurs primarily through the oxidative or nonoxidative pathways of glucose metabolism. We studied this question in 12 obese subjects [whose body mass index (BMI) was 33.4 +/- 1.1 kg/m2)] before and after 6 wk on a very-low-calorie diet of 1680 kJ/d with the euglycemic insulin clamp technique in combination with indirect calorimetry. The mean body weight decreased from 105.3 +/- 4.6 to 94.1 +/- 4.0 kg (P less than 0.001). This was mainly due to a reduction in fat mass from 47.2 +/- 3.6 to 37.7 +/- 3.0 kg (P less than 0.001), whereas lean body mass decreased only slightly (from 58.0 +/- 2.0 to 56.4 +/- 1.8 kg). The basal energy expenditure decreased with weight loss by 10.7%. This was associated with a reduced rate of lipid oxidation (P less than 0.05). Weight loss increased glucose utilization by 26%, primarily by enhancing insulin-stimulated glucose oxidation (P less than 0.05), whereas the effect on nonoxidative glucose metabolism was less pronounced (P greater than 0.05). Substantial weight loss increases glucose utilization by enhancing glucose oxidation. PMID- 1615893 TI - Protein metabolism in obese subjects during a very-low-energy diet. AB - We postulated that the return to nitrogen equilibrium after 3 wk of a negative balance during a very-low-calorie diet (VLCD) providing low-quality protein in obese subjects was due to availability of endogenously originating amino acids from a "pool" that, when depleted, would result in worsening balance. This should be reflected in altered kinetics of protein metabolism with the requirement for increased breakdown to maintain synthesis constant. Seven female obese subjects [body mass index (BMI) = 34.4 +/- 1.8 kg/m2] were given a 1.7-MJ/d all-protein diet (16.8 g N) derived from hydrolyzed gelatin (supplemented with tryptophan and methionine) that provides 18% of its amino acids as essential, a multivitamin mineral supplement, and 16 mmol KCl for 42 d. At baseline (7-d isocaloric diet), and weeks 4 and 6 of VLCD, amino nitrogen flux rate was calculated from the 15N abundance in urinary urea using the oral 15N-glycine method and rates of synthesis (S) and breakdown (B) inferred from N flux. Whole-body N flux did not change from baseline to weeks 4 and 6 (39.5 +/- 2.0 vs 37.4 +/- 2.0 vs 39.2 +/- 1.9 g N/d). By contrast, S and B decreased at weeks 4 and 6 with S decreasing more so that net protein synthesis (S-B) was less positive at week 4 than at baseline (2.2 +/- 0.2 and 0.9 +/- 0.3 g N/d; P less than 0.05) and became negative at week 6 (-0.9 +/- 0.2 g N/d; P less than 0.05). Concurrently, N equilibrium was achieved by week 4 but returned to negative balance by week 6.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615894 TI - Cholelithiasis in patients treated with a very-low-calorie diet. AB - One hundred seventy-nine obese patients (mean body mass index = 36.3) were retrospectively evaluated for the development of cholelithiasis associated with the use of a 2530-kJ/d (605-kcal) very-low-calorie diet (VLCD). Nine percent of patients had preexisting gallstones and 11% of patients developed gallstones either during or within 6 mo of completing the diet. Six percent had subsequent cholecystectomy. Ursodeoxycholic acid administered to one patient resulted in spontaneous stone dissolution whereas spontaneous dissolution occurred in three patients. Surveys of patients at three other programs using the same diet yielded similar incidence of gallstones. We conclude that rapid weight loss associated with the use of VLCD is associated with a significant incidence of gallstone formation. VLCD should be physician supervised because resolution of cholelithiasis spontaneously, with stone passage, or dissolution with ursodeoxycholic acid therapy may reduce the need for cholecystectomy. PMID- 1615895 TI - Dependence of weight loss during very-low-calorie diets on total energy expenditure rather than on resting metabolic rate, which is associated with fat free mass. AB - The assumption that total energy expended is related to resting metabolic rate (RMR) has not been validated. Intuitively, weight lost should be determined by the difference between the total energy consumed and the total energy expended. The ratio of actual daily energy usage to RMR by subjects dieting for 11 wk on a 1695-kJ (405-kcal) very-low-calorie diet (VLCD) was variable 1.9 +/- 0.3 (range 1.47-2.36). Weight loss correlated with total energy expenditure measured by 2H2 18O and not RMR, body mass index or body composition. Although RMR may be a reliable indicator of fat-free mass, there is little evidence that subjects with similar RMR will lose comparable weight or have comparable difficulty in weight maintenance. PMID- 1615896 TI - Changes in total body nitrogen during weight reduction by very-low-calorie diets. AB - Body composition measurements, including total body nitrogen (TBN) by in vivo neutron activation analysis, were made on 11 female volunteers before and after an 11-wk very-low-calorie diet (VLCD) [1695 kJ (405 kcal) 6.7 g N]. Mean body mass index (BMI) changed from 32.1 to 26.2 kg/m2, corresponding to a mean weight loss of 16.2 +/- 2.4 (SD) kg. The mean loss of TBN was 125 +/- 57 g, equivalent to 781 +/- 356 g protein. The fat-free mass (FFM) component of the weight loss was calculated by two different methods as 23.5% (+/- 3% SEM) and 22.8% (+/- 2.7% SEM), respectively, thereby demonstrating the improved protein sparing of ketogenic VLCDs. FFM loss was not clearly related to BMI. PMID- 1615897 TI - Altered calcium homeostasis accompanying changes of regional bone mineral during a very-low-calorie diet. AB - Calcium homeostasis during a very-low-calorie diet (VLCD) was examined. During the treatment, intact parathyroid hormone tended to decrease initially, bone Gla protein increased significantly in the third week, and tartrate-resistant acid phosphatase decreased during the entire treatment. Serum ketone bodies showed significant correlations with intact parathyroid hormone and bone Gla-protein in some cases. Regarding bone mineral content, bone mineral content of the head increased while that of the legs decreased, resulting in no significant changes in total bone mineral content. These results suggest that VLCD treatment alters calcium homeostasis, which may cause regional bone mineral changes. PMID- 1615898 TI - Lipid, lipoprotein, and apolipoprotein assessment during an 8-wk very-low-calorie diet. AB - The influence of a very-low-calorie diet (VLCD) on lipid pattern is controversial. To evaluate the long-term effect of semistarvation on lipid patterns, a group of severely obese patients [aged 37 +/- 12 y, body mass index (BMI) 40.0 +/- 0.9] underwent a VLCD for 8 wk. Total cholesterol (TC), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C), triglycerides (TGs), apolipoproteins A1 (apo A1) and B (apo B) were analyzed every week. TC (6.07 +/- 0.23 vs 5.53 +/- 0.25 mmol/L, P less than 0.0008), HDL-C (mmol/L 1.26 +/- 0.06 vs 1.04 +/- 0.05 mmol/L, P less than 0.0001), TGs (1.46 +/- 0.19 vs 1.06 +/- 0.10 mmol/L, P less than 0.0008), and apo A1 (1.57 +/- 0.06 vs 1.32 +/- 0.06 g/L, P less than 0.0002) decreased, whereas LDL-C and apo B showed a biphasic behavior: they significantly fell during the first 3 wk, but during the last weeks returned to their initial values. PMID- 1615899 TI - Clinical correlates of short- and long-term weight loss. AB - This study was designed to identify psychological, behavioral, and physiological correlates of short- and long-term weight loss. Measures of psychological functioning, body composition, fat cell size and number, and attendance were evaluated in 76 obese women for their relationship to weight loss at the end of treatment and at a 1-y follow-up evaluation. Losing more weight during the first month of treatment and attending a higher percentage of treatment sessions were strongly associated with greater weight loss at the end of treatment and at 1-y follow-up. In addition, patients with the highest initial weights lost the most weight both at the end of treatment and at 1-y follow-up. Easily obtained measures are as successful in predicting weight loss as are more expensive and complicated measures. PMID- 1615900 TI - Comparison of clinical usefulness of very-low-calorie diet and supplemental low calorie diet. AB - Forty-five overweight patients (12 male, 33 female) were prescribed a very-low calorie diet (VLCD) or a supplemental low-calorie diet (LCD), randomly, at an outpatient clinic. Twenty obese patients [31.6 +/- 13.1 y; body mass index (BMI) 32.9 +/- 6.1] were treated with a VLCD of 1757 kJ/d for 1-2 mo (five packages of Optifast 70/d; Sandoz Nutrition, Minneapolis). Another 25 patients (35.3 +/- 11.7 y; BMI 31.9 +/- 4.4) were treated by a supplemental LCD of 3515-5021 kJ/d for 1-2 months, which consisted of two to three packages of Optifast 70 and 2678-3682 kJ of conventional balanced meals. By the fourth week, the weight reduction obtained by the VLCD was significantly greater than that achieved by the supplemental LCD (P less than 0.01). At the eighth week, however, effect of the VLCD and the supplemental LCD in terms of weight reduction did not differ significantly. No serious side effects were observed in either treatment group. However, remarkable elevation of serum uric acid concentration was detected in seven patients on the VLCD. The treatment period of the VLCD is limited to less than or equal to 3 mo. On the other hand, obese patients can be treated with the supplemental LCD for greater than 3 mo. Therefore, the supplemental LCD is considered to be useful in the treatment of moderately obese Japanese patients on an outpatient basis. PMID- 1615901 TI - Across-the-day monitoring of mood and energy intake before, during, and after a very-low-calorie diet. AB - Mood, hunger, and energy intake were monitored in eight obese women before, during, and after 2 wk on a very-low-calorie diet (VLCD). Energy intake was significantly lower by approximately 30% in the week after the VLCD compared with the prediet week, both from food diaries and at a controlled ad libitum test meal. There was a gradual reduction in hunger, irritability, and urge to eat after 1 wk on the VLCD, which persisted through the postdiet week. Hunger and discontent were greatest in the evening during the first few days of the VLCD but diminished as the duration of the VLCD increased. PMID- 1615902 TI - Long-term outcome of a self-help very-low-calorie-diet weight-loss program. AB - This paper presents 90-wk data on five seriously overweight subjects originally brought together for 1-2 wk in simple residential accommodation to share the experience of beginning a program of very-low-calorie dieting. All subjects have remained well below their starting weight; four of the five subjects have continued to lose weight (weight losses 33.7-66.8 kg), now weighing less than at the end of the first 26 wk previously reported (1). It is proposed that this self help group model, incorporating a very-low-calorie diet, is valuable for the long term management of obesity. PMID- 1615903 TI - Effect of 4-wk treatment of obesity by very-low-calorie diet on anthropometric, metabolic, and hormonal indexes. AB - One-month treatment of obese patients (body mass index, 39.44 +/- 0.94, measured in kg/m2) with a very-low-calorie diet (VLCD) resulted in a significant weight loss, which was higher in men than in women. In contrast, the decrease of percent fat content was higher in gynoid obese women than in men or women with android fat distribution. In females fat mobilization was depressed at the thigh region where a substantially lower percent decrement of thigh skinfold thickness was demonstrated in comparison with males. VLCD treatment positively affected blood pressure and concentrations of total cholesterol, triglyceride, insulin, and cortisol. Total cholesterol-high-density-lipoprotein (HDL) cholesterol ratio remained unchanged and HDL cholesterol in serum significantly declined. Indexes of body fat distribution were not significantly influenced by the short-term treatment by VLCD except waist-hip ratio, which declined in android obese females. VLCD does not decrease a tolerance of physical exercise, as the metabolic response to submaximal workload on a cycle ergometer as well as the responses of cortisol, growth hormone, and prolactin remained unchanged after the treatment. PMID- 1615904 TI - Body-fat distribution and serum lipids during the long-term follow-up of obese patients treated initially with a very-low-calorie diet. AB - To evaluate a long-term efficacy of very-low-calorie-diet (VLCD) treatment, 42 obese patients were reexamined 1 y after the initiation of the weight reduction by VLCD treatment for 1 mo. All the subjects participating in the long-term outpatient weight-reduction regime were divided into weight losers and regainers according to the weight change achieved at the end of 1-y follow-up. A final body weight decrease in weight losers was followed by a significant decline of total cholesterol-high-density-lipoprotein (HDL) cholesterol ratio together with significant rise of serum HDL cholesterol whereas almost all skinfold thicknesses declined. In weight regainers the sum of 10 skinfold thicknesses was the same at the end of follow-up as at the beginning of VLCD treatment, but body fat distribution was shifted towards the gynoid type when individual skinfold thicknesses were assessed. However, among the generally employed indexes of body fat distribution only waist-thigh ratio significantly decreased in weight losers. Nonsignificant differences in serum concentrations of total cholesterol, HDL cholesterol, and triglycerides between weight regainers and weight losers at the end of long-term follow-up suggest that some kind of adherence to weight reduction regime including physical exercise may favorably affect the lipid profile as well as body fat distribution independently on the body weight regained. PMID- 1615905 TI - Body composition and weight maintenance with a very-low-calorie diet for the treatment of moderate obesity. AB - We report body composition in 11 moderately obese patients (mean BMI less than 30) treated for 8 wk with a 2530-kJ/d (605-Kcal) diet. Mean weight loss was 9.4 kg. Fat-free mass (FFM) loss of 2.3 kg was 23% of total weight loss and essentially equal to loss of total body water (2.5 L). Body composition was measured by the Futrex-5000 near-infrared technique. We conclude there is no excess loss of FFM in moderately obese patients treated with MNP 70/70, a 70-g protein, 70-g carbohydrate dietary supplement for 8 wk. PMID- 1615906 TI - Repeated use of the very-low-calorie diet in a structured multidisciplinary weight-management program. AB - Forty-eight obese patients (mean body mass index = 36.4) were retreated with a very-low-calorie diet (VLCD) at a mean of 104-wk after first VLCD. Mean weight regain was 23 kg or 86% regain of initial loss. Retreatment with VLCD required weekly physician monitoring and indepth psychotherapy group attendance. Five patients (10%) lost an average of 4.55 kg and withdrew within the first 4 wk (group AO. Thirteen patients (27%) lost 13.8 kg over 11.5 wk, an average weight loss of 1.2 kg/wk and enrolled in maintenance (group B). Thirty patients (63%) lost 10.2 kg over 20 wk, an average weight loss of 0.5 kg/wk and did not enroll in the maintenance program (group C). Although weight loss occurs in patients retreated with the VLCD, adherence to the VLCD and commitment to the maintenance program are not optimal. PMID- 1615907 TI - Comparative weight loss in obese patients restarting a supplemented very-low calorie diet. AB - Successive weight losses were compared for 21 patients restarting a very-low calorie diet (VLCD) after weight regain. Patients broke VLCD2 sooner (3.8 vs 9.8 wk) and lost less (9.4 vs 19.1 kg), but weight-loss rates did not differ significantly (0.83 vs 0.71 kg/wk). Net loss post-VLCD2 was 12.0 kg. Restart patients had difficulty adhering to the repeat VLCD, which resulted in lower losses. However, similar weight-loss rates and significant net weight loss suggest repeat VLCDs can be effective. PMID- 1615908 TI - Glycogen storage: illusions of easy weight loss, excessive weight regain, and distortions in estimates of body composition. AB - Glycogen is stored in the liver, muscles, and fat cells in hydrated form (three to four parts water) associated with potassium (0.45 mmol K/g glycogen). Total body potassium (TBK) changes early in very-low-calorie diets (VLCDs) primarily reflect glycogen storage. Potassium released from glycogen can distort estimates of body composition during dieting. TBK changes due to glycogen mobilization were measured in 11 subjects after 4 d dieting with a VLCD. The influence of water laden glycogen on weight fluctuations during the dieting process, the exaggerated regain if carbohydrate loading occurs, and the implications for weight control programs and overestimation of nitrogen losses with dieting are discussed. PMID- 1615909 TI - Outcome of a multicenter outpatient weight-management program including very-low calorie diet and exercise. AB - A 12-wk weight-management program was conducted to test the effectiveness of a combined very-low-calorie diet (VLCD) [2.0 MJ/d (470 kcal/d)] (week 1-5) and exercise (E) program supervised by each patient's general practitioner and dietitian. Throughout the program, patients [body mass index measured in kg/m2 (BMI) 27-35] were encouraged to take part in an individually graded E program of walking (W), cycling (C), running (R), or swimming (S) (Van Baak and Binkhorst 1981). Ninety-four patients (65 female and 29 male, weight: 87.7 kg, BMI: 30.7, age: 39.8 y) completed the program (delta: -10.6 kg). At the start, 46% were not involved in any type of physical exercise. After 12 wk only 8% were inactive (Drop out group (n = 14): 47%). Weight loss over 12 wk was significantly (P less than 0.01) related to participation rate in the E program. Also, 24-wk follow-up showed a significantly better (P less than 0.05) weight maintenance for patients who continued the E program (+0.4 vs +1.8 kg). These data demonstrate the effectiveness of a weight-management program including exercise in primary health care. PMID- 1615910 TI - High-density-lipoprotein metabolism during a very-low-calorie diet. AB - We examined the changes in high-density-lipoprotein (HDL) metabolism in eight female obese patients undergoing a very-low-calorie diet (VLCD). In the first half of the study, HDL cholesterol (HDL-C), apolipoprotein A-I (apo A-I), and apo A-II showed a parallel decrease. Although lipoprotein lipase (LPL) and hepatic lipase (HTGL) did not change, lecithin: cholesterol acyltransferase (LCAT) decreased. In the latter half of the protocol, HDL-C and apo A-I increased whereas apo A-II decreased, resulting in increased apo A-I-A-II ratios. There was no change in LPL, HTGL, or LCAT. LCAT and apolipoprotein composition may be important in HDL-C changes after VLCD. PMID- 1615912 TI - Perilous times in pathology education. PMID- 1615911 TI - Very-low-calorie-diet therapy in severe obesity. AB - This study investigated the effects of very-low-calorie-diet (VLCD) therapy on body weight, plasma glucose, and lipid metabolism in severely obese patients. Ninety-one patients were subjected to VLCD therapy for 4-24 wk. Reduction of body weight was remarkable during the first 4 wk, then leveled off despite continuous treatment. Fasting plasma glucose, triglyceride, and 75-g oral glucose-tolerance test showed a significant improvement. Total cholesterol fell in the early stages but then increased more than the pretreatment level during VLCD. VLCD therapy is useful for the treatment of severe obesity. PMID- 1615913 TI - Quantitation of estrogen and progesterone receptors by immunocytochemical and image analyses. AB - Compared to other techniques, the ability to detect estrogen and progesterone receptors by immunocytochemical analysis in formalin-fixed, paraffin-embedded sections has clear advantages, including the ability to assay small biopsy specimens, fine-needle aspirate samples, and archival material. Twenty-two cases of breast carcinoma were evaluated for estrogen and progesterone receptors by immunocytochemical analysis and enzyme immunoassay. Using a true color-based image analysis system, histograms of area versus the optical density of the positive staining nuclei were generated. A binary decision algorithm was derived from these histogram parameters by the CART computer program. Estimates generated by the algorithm for image analysis/immunocytochemical analysis had a 90% concordance with the enzyme immunoassay values. It is concluded that quantitative immunocytochemical results for estrogen and progesterone receptor content in formalin-fixed, paraffin-embedded tissue can be generated using image analysis. PMID- 1615914 TI - Multiple microcarcinoids arising in chronic ulcerative colitis. AB - A 50-year-old man who had chronic ulcerative colitis with dysplasia and two synchronous carcinomas had a total colectomy. Microscopic examination of the resected specimen revealed multiple microcarcinoids that were all smaller than 2 mm in diameter and not visible with gross examination. Histologic examination revealed that they were similar to microcarcinoids of the stomach encountered in patients with pernicious anemia. In this patient, however, there was no associated endocrine cell hyperplasia in the overlying mucosa, and the carcinoids may have arisen from dysplastic stem cells in the colonic crypts. PMID- 1615916 TI - Processing and evaluation of breast excision specimens. A clinically oriented approach. PMID- 1615915 TI - Positive immunoglobulin gene rearrangement study by the polymerase chain reaction in a colonic adenocarcinoma. AB - The detection of clonal rearrangements of the immunoglobulin heavy chain gene by the polymerase chain reaction provides a rapid method to differentiate monoclonal from polyclonal B-lymphocyte proliferations. It has been shown to be highly specific and so far, no false-positive results have been described. A case of a poorly differentiated colonic adenocarcinoma that showed a "false positive" clonal immunoglobulin heavy chain gene rearrangement by the polymerase chain reaction technique is reported. DNA contamination was unlikely because of the strict adherence to the laboratory polymerase chain reaction protocol and also the repeated demonstration of the same amplified band in a separate experiment using DNA extracted from another piece of tumor tissue. The apparent monoclonal immunoglobulin heavy chain gene rearrangement in the first polymerase chain reaction may be related to a combination of the paucity of lymphoid cells in the tissue sample and the presence within this small number of lymphocytes of a clonal reactive cell population. It is, therefore, important to correlate the routine microscopic and immunohistochemical findings in the interpretation of polymerase chain reaction results, especially when working with nonlymphoid tumors and lymphocyte-poor lesions. PMID- 1615917 TI - Detection of Pneumocystis carinii. Comparative study of monoclonal antibody and silver staining. AB - The sensitivity of Pneumocystis carinii detection using silver stain (Grocott method) was compared to that using the avidin-biotin-complex immunoperoxidase (IP) staining method with anti-P. carinii monoclonal antibody. Silver stain detected only cyst wall, whereas IP stained both cyst wall and trophozoites. Serial sections of formalin-fixed, paraffin-embedded autopsy lung specimens from 41 acquired immune deficiency syndrome patients in three disease categories were stained: I--premortem or autopsy diagnosis of P. carinii pneumonia (13 cases); II -history of treated P. carinii pneumonia but no P. carinii detected in autopsy tissue specimens (15 cases); and III--no clinical or autopsy evidence of P. carinii pneumonia (13 cases). Smears from 7 bronchoalveolar lavages (3 positive) and 11 induced sputa (1 positive) also were stained. All cases of P. carinii in category I were detected with equal sensitivity. P. carinii undetected by silver stain in category II and III cases and in bronchoalveolar lavages and induced sputa were not revealed by IP. Detection of trophozoites by IP did not improve sensitivity because the staining pattern was amorphous or focally granular, and thus easily confused with nonspecific staining of mucin or intracellular or free particulate material. Reliable identification of trophozoites could be made only with coexisting cyst structures. Silver staining was more advantageous because it also identified fungal infections and was faster and more cost effective than IP. PMID- 1615918 TI - Antibodies reactive with T cells in paraffin sections. PMID- 1615919 TI - Small blastoid cells in bone marrow. PMID- 1615920 TI - Frequency of gastric intestinal-type and diffuse-type adenocarcinoma in Mexico. PMID- 1615921 TI - Increased free phenytoin concentrations in predialysis serum compared to postdialysis serum in patients with uremia treated with hemodialysis. Role of uremic compounds. AB - Patients with uremia are reported to have elevated concentrations of free phenytoin as a result of decreases in protein binding. This appears to be related to the presence of uremic compounds. To determine the dialyzability of these compounds, the in vitro protein binding levels of phenytoin in pre- and postdialysis serum (supplemented with phenytoin) of 12 patients with uremia were compared. For these patients, the concentrations of free phenytoin were significantly greater in predialysis serum (lower protein binding) compared to postdialysis serum, although the concentrations of total phenytoin did not vary. Low levels of protein binding of phenytoin in predialysis serum also were observed in two hemodialysis patients receiving phenytoin. Several serum pools, prepared from both normal volunteers and the predialysis sera of uremic patients, were dialyzed (in vitro equilibrium dialysis). Then both undialyzed and dialyzed sera were supplemented with phenytoin and analyzed to determine free and total phenytoin concentrations. The free phenytoin concentrations were increased in equilibrium-dialyzed normal serum pools compared to undialyzed original pools because of decreases in albumin concentrations after equilibrium dialysis. In contrast, free phenytoin concentrations were decreased in the equilibrium dialyzed uremic serum pools, thereby indicating an attenuation of the albumin dilution effect on free phenytoin concentration, probably by the preexisting uremic compounds. These compounds can be removed completely by treating sera with activated charcoal at pH 3. The results obtained from charcoal treatment experiments, in combination with other results, indicate that these uremic compounds can be removed partially by in vivo hemodialysis and by in vitro equilibrium dialysis. PMID- 1615922 TI - Hairy cell leukemia. Diagnosis of bone marrow involvement in paraffin-embedded sections with monoclonal antibody DBA.44. AB - The new monoclonal antibody DBA.44 recognizes an unknown fixation-resistant B cell differentiation antigen expressed by mantle zone lymphocytes, reactive immunoblasts, monocytoid B cells, and a small proportion of high- and low-grade lymphomas. Among node-based lymphomas, the strongest membrane staining was observed in centroblastic, immunoblastic, and monocytoid B-cell lymphomas. In studying bone marrow biopsy specimens from 166 patients with hairy cell leukemia, strong positive staining of surface membrane 'hairy' features of leukemic cells was observed in routinely fixed and decalcified bone marrow biopsy specimens of nearly all cases. The antibody distinguished hairy cell leukemia from the more common B-cell chronic lymphocytic leukemia and bone marrow infiltrates of typical lymph node-based lymphomas by immunomorphologic criteria. DBA.44 was valuable to (1) confirm the diagnosis of hairy cell leukemia, (2) estimate the bone marrow density of hairy cell leukemia before and after treatment, and (3) make the diagnosis of hairy cell leukemia in ambiguous cases, which are all properties that indicate its usefulness in the practice of diagnostic hematopathology. PMID- 1615923 TI - The prognostic significance of proerythroblasts in acute erythroleukemia. AB - Erythroleukemia is a heterogeneous disorder that can have an excess of myeloblasts or proerythroblasts in the setting of dyserythropoiesis. The French American-British classification, established in 1976 and subsequently revised, allows only for the diagnosis of erythroleukemias whose immature elements are predominated by myeloid blasts, previously described as DiGuglielmo's syndrome. However, there is another form of erythroleukemia, in which the predominant immature elements are proerythroblasts, called DiGuglielmo's disease. To clarify this issue, 23 cases of erythroleukemia were reviewed and classified: 10 with a myeloblast predominance and 13 with a proerythroblastic predominance. These two forms of erythroleukemia can be distinguished on the basis of quantitative and qualitative morphologic features. When there were 30% or more proerythroblasts, calculated by dividing the total erythroid component into the proerythroblasts, there were few to no myeloblasts, no Auer rods, and increased cytoplasmic vacuoles; and myeloperoxidase staining was negative. The malignant proerythroblasts had increased block and blush periodic acid-Schiff positivity. The most frequent chromosomal abnormalities involved chromosomes 5 and 7. The patients with DiGuglielmo's disease had a median survival time of 2 months (range, 0.06 to 9 months), compared to a median of 16 months (range, 2 to 48 months), in patients with DiGuglielmo's syndrome. The erythroleukemia with the preponderance of proerythroblasts had a worse prognosis because many of the individuals did not survive long enough to respond to the therapy initiated. Erythroleukemia with 30% or more proerythroblasts should be included in the French-American-British classification because it behaves clinically and appears morphologically as an acute leukemia rather than a myelodysplastic syndrome. PMID- 1615924 TI - Acute monocytic leukemia with chloroacetate esterase positivity. FAB M4 or M5? AB - French-American-British criteria for the diagnosis of acute monocytic leukemia (M5) require that 80% of nonerythroid bone marrow cells consist of monoblasts, promonocytes, and/or monocytes. Monocytic differentiation is demonstrated by fluoride-sensitive nonspecific esterase positivity. Chloroacetate esterase positivity is accepted as a marker of granulocytic differentiation. Three cases fulfilling French-American-British criteria for M5 showed fluoride-sensitive nonspecific esterase positivity in up to 100% of nonerythroid marrow cells but also exhibited strong chloroacetate esterase positivity in 20% to 90% of the same population. Less than 5% of blasts stained for Sudan black B and peroxidase. These cases may be viewed as chloroacetic esterase-positive acute monocytic leukemia or as acute myelomonocytic leukemia. The authors favor the former because the cases were myeloperoxidase negative; however, these cases indicate that chloroacetate esterase may not be a specific marker for granulocytic differentiation. PMID- 1615925 TI - DNA analysis to aid in the diagnosis of chronic myeloproliferative disorders. AB - Diagnosing chronic myeloproliferative disorders (CMPD) can be difficult because of overlap and possible transitions between the different conditions and their similarity to reactive myeloproliferations. DNA analysis was applied to improve differentiation of CMPDs. All subtypes of CMPD analyzed, including chronic myeloid leukemia, agnogenic myeloid metaplasia, polycythemia vera, and essential thrombocythemia, had in common that granulocytes and bone marrow cells were clonal in origin, as shown by X chromosome-linked DNA polymorphism in conjunction with methylation patterns (n = 32). Reactive myeloproliferations, by contrast, showed polyclonal inactivation patterns. Clonality could not distinguish CMPD from cases of myelodysplastic syndrome because the latter (n = 7) also exhibited clonal hematopoiesis. Because of their clonal origin, peripheral granulocytes were used in all cases (n = 201) to detect bcr gene rearrangement. Despite possible morphologic overlap between different types of CMPD, bcr gene rearrangement was specific for chronic myeloid leukemia and could be applied to differentiate chronic myeloid leukemia from other CMPDs in cases of equivocal morphologic diagnosis. Chronic myeloproliferative disorders represent clonal hemopoietic diseases that probably have specific underlying genetic defects. Thus DNA analysis can aid substantially in the differential diagnosis of CMPD. PMID- 1615926 TI - Barrett's esophagus. A preneoplastic disorder. PMID- 1615927 TI - Acute megakaryoblastic leukemia simulating carcinoma. AB - Acute megakaryoblastic leukemia has emerged as an important subset of early childhood leukemia. It often presents a diagnostic dilemma because of its many morphologic manifestations and propensity to mimic metastatic carcinoma. An abdominal mass was identified by sonographic and computed tomographic scans in a 10-month-old girl, who had anemia and thrombocytopenia. An open biopsy of the 3 cm, peripancreatic mass showed cohesive nests and sheets of tumor cells with focal spindling and desmoplasia. Although the diagnosis of acute megakaryoblastic leukemia was established from a bone marrow aspirate using immunocytochemical techniques and karyotype analysis, a coexistent abdominal epithelial malignant neoplasm could not be excluded entirely by light microscopic examination alone. The megakaryoblastic nature of the abdominal tumor was established by immunocytochemical stains for glycoprotein IIIa on paraffin-embedded tissue. PMID- 1615928 TI - Mucin histochemical analysis in the interpretation of Barrett's esophagus. Results of a multicenter study. The Operative Group for the Study of Esophageal Precancer. AB - A multicentric study of Barrett's esophagus (BE) was started in November 1987 to evaluate (1) the prevalence of BE among subjects undergoing upper gastrointestinal endoscopic examination; (2) the pathologic features of BE; and (3) the correlation between BE and early malignant changes. In 157 of 330 patients who underwent multiple standardized biopsies, BE was confirmed with histologic evaluation. Specialized intestinal-type BE was observed in 84 patients. By applying Alcian blue (pH 2.5)-periodate oxidation-Schiff, high-iron diamine-Alcian blue (pH 2.5), and periodate borohydride-saponification-periodate oxidation-Schiff techniques, the intestinal type of BE was subclassified into colonic and ileal types, both complete and incomplete. Fifty cases had incomplete colonic metaplasia with sulphomucins in the columnar cells and 64 had complete colonic intestinal metaplasia, 49 of them containing O-acetylated sialomucins in the goblet cells. These patients are being included in a short-term follow-up. Dysplasia (six low grade, two high grade) was observed in eight patients in areas of intestinal colonic-type epithelium; in these patients, a complete loss of O acetylated sialomucins in the dysplastic areas and a remarkable reduction of these mucins in the surrounding tissue were observed. The reduction of O acetylated sialomucins might indicate relative tissue immaturity, which could represent an early sign of neoplastic dedifferentiation. Therefore, the relevance of O-acetylated sialomucin content in BE, first demonstrated in intestinal type, is now evident, although its biologic importance is being studied. PMID- 1615929 TI - Expression of blood group-related antigens, ABH, Lewis(a), Lewis(b), Lewis(x), Lewis(y), CA19-9, and CSLEX1 in early cancer, intestinal metaplasia, and uninvolved mucosa of the stomach. AB - The expression of blood group-related antigens, A, B, H type 2, Lewis type 1 (Lewis(a) [Le(a)] and Lewis(b) [Le(b)]), Lewis type 2 (Lewis(x) [Le(x)] and Lewis(y) [Le(y)]), sialylated Le(a) (CA19-9), and sialylated Le(x) (CSLEX1), was analyzed sequentially with immunohistochemical methods in early gastric cancer, intestinal metaplasia, and uninvolved gastric mucosa obtained from 35 surgical specimens of patients who underwent gastrectomy. The high incidence of the inappropriate expression of Lewis type 1 antigens and the deletion of H and Lewis type 2 antigens was observed similarly in patients with cancer and intestinal metaplasia. The acquisition of CA19-9 and CSLEX1 and the deletion of B antigen frequently were found in intestinal-type cancer and all types of intestinal metaplasia. The simultaneous deletion of A antigen was detected only in the combination of intestinal-type cancer and incomplete-type intestinal metaplasia. Thus the present study shows that similar changes of tissue antigenicities exist in early gastric cancer and intestinal metaplasia. PMID- 1615930 TI - Expression of E-cadherin in normal, benign, and malignant tissues of female genital organs. AB - The expression of human E-cadherin in normal tissues and in benign and malignant tumors of female genital organs was examined immunohistochemically with a monoclonal antibody, HECD-1, specific for human E-cadherin. The normal tissues included the ovary, fallopian tube, uterine endometrium, uterine cervix, and vagina. E-cadherin was detected clearly in the cell-to-cell boundaries of both normal glandular and squamous epithelia obtained from those tissues. The tumor tissues consisted of 9 ovarian, 7 endometrial, and 4 cervical adenocarcinomas, 12 squamous cell carcinomas of the cervix, including 3 cervical intraepithelial neoplasms, and 5 mesenchymal tumors. E-cadherin also was detected in the cell-to cell borders of all the epithelial tumors tested, with some reactivity in the cytoplasm of malignant cells, whereas mesenchymal tumors showed no expression. It is noteworthy that poorly differentiated areas of both the adenocarcinomas and squamous cell carcinomas showed less expression of E-cadherin. No difference in the expression of E-cadherin between the primary and metastatic lesions was detected in 10 sets of malignant tumors. E-cadherin may be an important factor among a variety of biologic events that occur during the process of metastasis. However, further studies are needed to clarify this. PMID- 1615931 TI - p53 expression in neoplasms of the uterine corpus. AB - It has been recognized that mutations in tumor suppressor genes may have an important oncogenic role. Although abnormalities of the p53 tumor suppressor gene have been reported in tumors from various organ systems, p53 expression has not been studied in neoplasms of the uterine corpus. Using a monoclonal antibody to the p53 product, frozen sections of 56 uterine tumors (40 endometrioid endometrial adenocarcinomas, 7 serous endometrial carcinomas, 4 mixed Mullerian tumors, 2 endometrial stromal sarcomas, 1 leiomyosarcoma, 2 leiomyomas) and 2 normal endometria were stained using the immunoperoxidase technique. Staining was evaluated by light microscopic examination; in carcinomas with strong/diffuse reactivity, evaluation was by digitized image analysis. p53 staining of adenocarcinomas was compared statistically to the histologic type, grade, surgical stage, and clinical follow-up. Specific staining was present in the nucleus of malignant tumor cells only. Benign cells did not stain. Strong/diffuse staining was seen in 14 adenocarcinomas and in 2 mixed Mullerian tumors. Weak/focal staining was observed in 14 adenocarcinomas. Serous carcinomas showed strong positivity more frequently than endometrioid endometrial carcinomas. Staining patterns correlated with histologic grade and stage. Image analysis of immunostained p53 correlated with type of adenocarcinoma, but not with grade or stage in the cases measured. p53 was expressed strongly in tumors of five of eight patients who died of adenocarcinoma but in none of five patients with no evidence of disease and a minimum follow-up of 24 months. In addition, 3 of 12 patients with persistent or recurrent disease showed tumors that strongly expressed p53. It is concluded that abnormal expression of p53 occurs frequently in malignant uterine tumors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1615932 TI - Neuroendocrine phenotype in lung cancers. Comparison of immunohistochemistry with biochemical determination of enolase isoenzymes. AB - The authors evaluated methods of recognition of neuroendocrine differentiation in lung cancer because this is thought to bear prognostic value. One hundred forty lung tumors were divided by immunohistochemical analysis using neuroendocrine markers (neuron-specific enolase, Leu7, chromogranin, neural cell adhesion molecules, SL11/14, and Leu19) into two groups of 51 neuroendocrine tumors positive for three neuroendocrine markers and 89 non-neuroendocrine tumors. Biochemical determination of enolase activity and isoenzyme distribution showed that the level of total enolase activity was similar between neuroendocrine and non-neuroendocrine tumors. alpha gamma and gamma gamma enolase isoenzyme percentages were higher in neuroendocrine tumors. A cut-off of gamma enolase % (alpha gamma/2 + gamma gamma) at 14% gave a sensitivity rate of 84% and specificity rate of 97% in separating neuroendocrine and non-neuroendocrine tumors, whereas immunohistochemical analysis using anti-gamma enolase had low specificity (68%) and immunohistochemical analysis with Leu 7 and chromogranin had high specificity (97%) and low sensitivity (37% and 60%) levels for neuroendocrine tumors. The best prediction of neuroendocrine differentiation was obtained using immunohistochemical analysis against neural cell adhesion molecules combined with biochemical estimation of enolase using gamma enolase of 14% and a gamma gamma isoenzyme more than 3%. PMID- 1615933 TI - Optimization of DNA extraction from formalin-fixed tissue and its clinical application in Duchenne muscular dystrophy. AB - The authors report a case of Duchenne muscular dystrophy in which a deletion was determined by multiplex polymerase chain reaction using postmortem tissue from a proband who died in 1985, 2 years before the cloning of the dystrophin gene. Several extraction methods were analyzed to determine optimal conditions for recovery of DNA from fixed tissue. Variables examined were tissue lysis times and temperatures, a simple salting-out procedure for purification of DNA, polymerase chain reaction amplification of crude lysate versus purified DNA, and lysis of different tissues and tissue quantities. Extracted DNA was analyzed spectrophotometrically, electrophoretically, and by its suitability for polymerase chain reaction amplification using exon flanking primers of the dystrophin gene. Lysis at 37 degrees C for less than 24 hours led to the recovery of predominantly low-molecular-weight DNA, which was unsuitable for polymerase chain reaction in this experience. Lysis at 54 degrees C consistently yielded visible, spoolable quantities of high-molecular-weight DNA in as little as 24 hours. Direct amplification of crude, unpurified lysates was unsuccessful. However, purified samples yielded consistent amplification products. The purification step was simplified by substituting a rapid salting-out procedure for organic extractions. PMID- 1615934 TI - The high mortality of gastrointestinal bleeding in HIV-seropositive patients: a multivariate analysis of risk factors and warning signs of mortality in 50 consecutive patients. AB - The patterns of which human immunodeficiency virus (HIV)-seropositive patients underwent endoscopy for gastrointestinal bleeding at a university hospital were analyzed in 50 consecutive patients admitted from July 1984 through December 1989, and criteria were developed as to which patients are most likely to benefit from endoscopy. Analyzed patient data included the medical records, follow-up until July 1990 obtained by telephone questionnaire in 46 patients, and autopsy findings in the 11 patients undergoing autopsy. Thirty-seven percent of the patients did not undergo endoscopic or radiographic examinations indicated to determine the cause of bleeding. The adequacy of the evaluation was not related to race, intravenous drug abuse, homosexuality, hemophilia, the diagnosis of known AIDS, or being a public patient. In 21 of the 28 cases in which the cause of bleeding was determined, the diagnosed lesions had a specific, effective therapy. The mortality from gastrointestinal bleeding was 39.0%, compared with 8.3% in 48 controls without known HIV infection (p less than 0.001 by Fisher's exact test, odds ratio = 7.0, odds ratio confidence interval = 5.0-9.7). Statistically significant independent predictors of mortality included leukocytosis, concurrent major diseases, intravenous drug abuse, transfusion of 5 or more units of packed erythrocytes, and the presence of a bloody nasogastric aspirate or hematemesis (Wilk's lambda statistic = 0.369, p less than 0.0001). In particular, 10 of 11 patients (89%) with two or more concurrent major diseases died, whereas only three of 24 patients (13%) with no concurrent diseases died during the hospitalization. We conclude a large percentage of HIV-seropositive patients did not undergo a diagnostic evaluation for gastrointestinal bleeding at a university hospital, and there was no discernible rational pattern as to which patients underwent endoscopy. Endoscopy is an important and indicated procedure in HIV-seropositive patients with no or one concomitant major illness. HIV seropositive patients with gastrointestinal bleeding and two or more concomitant major illnesses have an exceedingly poor prognosis, and are less likely to benefit from invasive diagnostic tests and aggressive therapy. PMID- 1615935 TI - Long-term clinical and manometric follow-up of patients with nonspecific esophageal motor disorders. AB - In the manometric evaluation of patients complaining of chest pain, a nonspecific esophageal motor disorder is commonly identified. Yet, the clinical characteristics of these patients and stability of the manometric pattern with time have not been previously described. This study reports a 3.2-yr clinical and manometric follow-up of 23 patients with nonspecific esophageal motor disorder. These subjects were most commonly middle-aged women with long-standing, persistent, and debilitating clinical symptoms. Ninety-six percent (22/23) of our patients complained of chest pain; 65% (15/23) had dysphagia. In addition, 15 (65%) had evidence of reflux during ambulatory pH studies. Symptoms caused such concern that the patients frequently sought medical assistance to exclude serious diseases. Although the symptoms tended to persist, the motility patterns changed in some patients. Follow-up manometric studies were normal in 29%, and nonspecific esophageal motor disorder persisted in 57% of the patients. In three patients (14%), the pattern evolved into diffuse esophageal spasm. When symptoms were compared with these changes in follow-up manometric patterns, the correlation was poor. This observation suggests that additional mechanism(s) other than disturbed esophageal motility may be responsible for the symptoms seen in these individuals. PMID- 1615936 TI - Ischemic hepatitis: widening horizons. AB - Ischemic hepatitis is not an uncommon complication of reversible severe hypotension or cardiac failure. The prognosis usually is determined by the cause of the initial hypotension or cardiac failure, rather than the subsequent hepatic dysfunction. We report a retrospective analysis of nine patients with ischemic hepatitis in which previously unreported clinical and biochemical abnormalities are noted. The clinical and biochemical course of the patients were reviewed until recovery or death from ischemic hepatitis. All the patients had a rapid striking elevation of aspartate aminotransferase, and lactic dehydrogenase, with an equally rapid resolution of these parameters. Abnormal serum glucose levels occurred in six patients (none of whom had a prior carbohydrate intolerance). Insulin therapy was given to three patients for a limited period. Renal impairment was manifest in all nine patients, and it resolved spontaneously within 10 days. Altered mental status was detected in six patients; the changes reverted to normal within 7 days of their onset. A preexisting anemia (hemoglobin less than 11.0 g/dl) was noted on admission in four patients, and it did not appear to potentiate the manifestations of the hepatic ischemia. We conclude that ischemic hepatitis should be anticipated in all patients with a recent history of systemic hypotension. It should be considered in the differential diagnosis of patients with unexplained hepatitis; the early massive rise in lactic dehydrogenase, the rapid fall in transaminases, and the early mild/moderate renal failure strongly suggest ischemic hepatitis. Patients with ischemic hepatitis can manifest reversible renal failure, mental confusion, and hyperglycemia which may require insulin for its control. PMID- 1615937 TI - Effect of injection sclerosis with alcohol on the rebleeding rate of gastroduodenal peptic ulcers with nonbleeding visible vessels: a prospective, controlled trial. AB - To assess the efficacy of injection therapy with alcohol on prevent rebleeding and emergency surgery in patients with gastroduodenal ulcers and nonbleeding visible vessels, we have performed a prospective controlled trial involving 39 patients who were classified into two groups according to the time of the day on which emergency endoscopy was performed: group 1 (25 patients) in which endoscopic hemostasis with absolute alcohol was performed, and group 2 (14 patients) in which conventional therapy was applied (blood transfusions, antacids, and ranitidine). The two groups were comparable with regard to age, sex, and type of bleeding. The rebleeding rate/emergency surgery rate of 8%/4%, respectively, for group 1 was lower than the 57%/50% for group 2 (p less than 0.001). Our results suggest that endoscopic hemostasis with alcohol should be considered as the initial treatment of choice in patients who present with major upper gastrointestinal hemorrhage and are found to have an ulcer with a nonbleeding visible vessel. PMID- 1615938 TI - Fecal protein markers of colorectal cancer. AB - To identify fecal proteins that might prove useful in the early detection of colorectal cancer, we used sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and protein immunoblotting to compare the fecal protein patterns of stool supernatants from 10 patients with colorectal cancer with those of 12 controls. SDS-PAGE followed by Coomassie blue staining revealed two heavily stained bands in the majority of cancer stools that were not present in control stools. These bands proved to be human hemoglobin and human albumin by protein immunoblotting. No other consistent differences between the cancer and control stools were observed on the stained gels. The stool supernatants were probed for several other blood proteins by protein immunoblotting. Carbonic anhydrases I and II were more abundant in the cancer stools; alpha 1-antitrypsin appeared equally in cancer and control stools. Further work is needed to determine whether measurement of fecal carbonic anhydrase can be useful for early detection of colorectal cancer. PMID- 1615939 TI - Correlates of constipation in an ambulatory elderly population. AB - Constipation is a common and often perplexing problem for elderly people. The prevalence of self-reported constipation and factors associated with constipation were investigated in 3,166 people over age 65. Twenty-six percent of women and 15.8% of men reported recurrent constipation (p less than 0.0001). There was a significant increase in reported constipation with increasing age (p less than 0.0001). Multiple factors were found to correlate with self-reported constipation. A logistic regression model revealed 13 factors of significance in predicting constipation. The most important factors were age, sex, total number of drugs taken, pain in the abdomen, and hemorrhoids (p less than 0.0001). Specific drugs do not appear to be important factors in constipation in the elderly. Elderly people who report the use of multiple drugs, pain in the abdomen, and hemorrhoids are at increased risk for constipation. PMID- 1615941 TI - Significance of pleural effusion in patients with acute pancreatitis. AB - We retrospectively reviewed the charts of all patients with acute pancreatitis admitted to our hospital between July 1987 and June 1991 to determine the relationship of a pleural effusion in patients with acute pancreatitis with the severity of the disease, the etiology of the pancreatitis, pseudocyst formation, and triglyceride levels. Eleven (13.4%) of the 82 patients with acute pancreatitis had evidence of pleural effusion. Eight of 42 patients with alcoholic pancreatitis developed an effusion, compared with one of 33 patients with biliary pancreatitis, indicating that an alcoholic etiology may be a risk factor. Seven (63%) of the 11 patients had associated pseudocysts. Patients with severe disease had a greater incidence of pleural effusion. The effusion was on the left side in six, bilateral in four, and on the right side in one patient. Hypertriglyceridemia did not appear to be an independent risk factor associated with pleural effusions. Diagnostic thoracentesis was performed in three patients because of the presence of fever. Pleural fluid amylase was normal in one case and mildly elevated in the other two. All effusions resolved spontaneously without the need for any therapeutic intervention. PMID- 1615940 TI - Receptor index via hepatic asialoglycoprotein receptor imaging: correlation with chronic hepatocellular damage. AB - Galactosyl human serum albumin is a newly developed receptor-binding agent, specific for the asialoglycoprotein receptor, which resides exclusively on the plasma membrane of mammalian hepatocytes. The receptor-binding agent was synthesized by the covalent coupling of carbohydrate units to human serum albumin. The clinical utility of technetium-99m-labeled galactosyl human serum albumin was evaluated in six control subjects with normal livers and in 50 patients with chronic liver disease. The parameter, receptor index, was derived from liver and heart time-activity data and is the ratio of radioactivity of the liver over the radioactivity of the liver plus the heart at 15 min after the intravenous injection of 3 mg of labeled ligand. Values for the receptor index in the control subjects and in patients with mild, moderate, and severe liver disease were 0.936 +/- 0.015, 0.909 +/- 0.034, 0.848 +/- 0.070, and 0.669 +/- 0.085, respectively. Good correlations were obtained between the receptor index and conventional liver function tests, such as the Child-Turcotte criteria score (rs = -0.776, p = 0.0001), prothrombin time (r = 0.736, p = 0.0001), and the plasma disappearance rate of indocyanine green (r = 0.805, p = 0.0001). These significantly high correlations of the receptor index with classical indicators of hepatic functional reserve suggest that the receptor index is a potentially practical and reliable diagnostic method for estimating the functioning hepatocyte mass and for assessing liver function. PMID- 1615942 TI - Primary gastric plasmacytoma: a morphological and immunohistochemical study of five cases. AB - Five cases of primary gastric plasmacytoma were studied histopathologically and immunohistochemically. Plasmacytoid cells proliferated diffusely in the propria mucosa, almost preserving the structure of gastric glands. Occasionally, intranuclear inclusions, giant cells, and needle-shaped crystalline inclusions were observed. The neoplastic nature could be suspected on the basis of these histological findings. Immunohistochemically, three cases were positive for IgM and two for IgA. IgM positivity was more commonly observed in the gastric plasmacytoma than in multiple myeloma. Another immunohistochemical study demonstrated that LN-1 negativity and anti-EMA antibody positivity might be an indicator to differentiate gastric plasmacytoma from other types of gastric lymphoma. Four cases of early-stage gastric plasmacytoma have been followed for 5 12 yr. No recurrence has been observed so far. These cases suggest that gastric plasmacytoma has a relatively good prognosis. PMID- 1615943 TI - Increased intracranial pressure and hepatic encephalopathy in chronic liver disease. AB - Increased intracranial pressure is present in more than 80% of patients with fulminant hepatic failure. However, patients with encephalopathy secondary to chronic liver disease are thought not to develop elevated intracranial pressure. We report two patients with chronic liver disease in hepatic coma with raised intracranial pressure documented by an epidural intracranial pressure monitor. One patient rapidly deteriorated to coma over a period of 4 h. The other patient progressively worsened following intravenous sedation administered during upper endoscopy. Both patients had generalized tonic-clonic seizures, and one demonstrated decerebrate posturing and papilledema. Although all metabolic and structural abnormalities should be excluded in patients with hepatic encephalopathy, if the etiology remains in question, the possibility of increased intracranial pressure should be considered in patients with chronic liver disease. PMID- 1615944 TI - Fungemia with Torulopsis glabrata after endoscopic biliary stent replacement. AB - We report a patient with disseminated cholangiocarcinoma who developed systemic fungemia subsequent to endoscopic retrograde cholangiopancreatography (ERCP) and stent replacement. Despite intensive systemic antifungal therapy with iv amphotericin B, the patient developed multiple complications and eventually succumbed to her underlying disease. Cultures of the removed stent and blood were positive for the same organism, Torulopsis glabrata. In an immunocompromised host during ERCP manipulation, fungal pathogens should be considered in post-stent septicemia. PMID- 1615945 TI - Aminophylline suppository-induced acute proctitis. AB - A 9-yr-old boy revealed anal hemorrhage after administration of an aminophylline suppository. Proctosigmoidoscopy demonstrated edema of the rectal mucosa with hyperemia and petechiae. We performed a provocation test and obtained the diagnosis of aminophylline suppository-induced acute hemorrhagic proctitis. One should recognize that acute hemorrhagic proctitis is a rare but important side effect of aminophylline suppositories, because they are commonly used for asthmatic children. PMID- 1615946 TI - Long-term hepatic memory for hypersensitivity to nitrofurantoin. AB - Nitrofurantoin-induced hepatic injury has been established unequivocally as an entity by rechallenge experiences. We reviewed 12 previously reported cases in which rechallenge was described. The longest reported interval between initial injury and rechallenge-provoked injury was 4 yr. We report a 56-yr-old woman who experienced severe hepatocellular injury with brief low-dose administration of nitrofurantoin 17 yr after an initial hepatitis-like illness associated with ingestion of the drug. Despite a temporal relationship to nitrofurantoin administration and histologic features compatible with drug-induced hepatitis, the initial bout of hepatitis had been termed "infectious." Our case appears remarkable for the long interval between initial injury and rechallenge-induced injury. The severity of the hepatic injury seen on rechallenge underscores the concept that the inadvertent rechallenge can be dangerous. Failure to identify the first bout of hepatitis as nitrofurantoin-related, and failure to inform the patient about the possible relationship to nitrofurantoin, raises important risk management concerns, because hepatic memory of nitrofurantoin hypersensitivity appears to be of long duration. PMID- 1615947 TI - Primary intestinal lymphoma in Crohn's disease: minute tumor with a fatal outcome. AB - A 54-yr-old man with a 22-yr history of Crohn's disease was found to have a microscopic focus of immunoblastic lymphoma within a segment of small bowel resected to relieve intestinal obstruction. There was no other clinically evident disease. Thirty months later, he developed axillary adenopathy with recurrent lymphoma of the same immunophenotype (IgA lambda) and was given combination chemotherapy, with complete clinical response. Lymphoma recurred 6 months later in the axilla and progressed rapidly over the next 3 months, despite chemotherapy. He developed extensive mediastinal, mesenteric, and retroperitoneal disease with malignant ascites and died 39 months after diagnosis of the incidentally discovered bowel mucosal primary tumor. PMID- 1615949 TI - Hepatic lymphangiomatosis: report of two cases, with an immunohistochemical study. AB - Two cases of hepatic lymphangiomatosis were examined. One tumor was noted incidentally at autopsy, and the other tumor was removed by operation. These liver tumors could not be detected by the naked eye, but ill-defined lace-like areas were seen. Microscopically, small cystic spaces were irregularly aggregated in the hepatic parenchyma and, in part, in the portal tracts. Faintly stained lymph-like material without any erythrocytes was found in the spaces. The silver impregnation method confirmed that most of the cystic lumina were dilated Disse's spaces. Also, some of them were directly connected with lymph vessels in the portal tracts. Thin lining cells along the internal surface of these cystic channels could not be positively stained by Ulex europaens 1 or factor 8-related antigen, both of which were present in the endothelium of the blood vessels in the portal tracts. We describe herein this rare lymphangiomatosis of the liver, with special reference to its immunohistochemistry. PMID- 1615948 TI - Acute colonic diverticular perforation presenting as left ear pain and facial swelling due to cervical subcutaneous emphysema in a patient administered corticosteroids. AB - A 56-yr-old white female administered corticosteroids presented with left ear pain and facial swelling due to cervical subcutaneous emphysema from a diverticular perforation of the sigmoid colon. This case demonstrates that localized signs of a bowel perforation may be absent in patients administered corticosteroids, that these patients may present with unusual, remote findings, and that bowel perforation can produce cervical subcutaneous emphysema. PMID- 1615950 TI - Adenocarcinoma in Meckel's diverticulum: report of a case and review of 30 cases in the English and Japanese literature. AB - A 54-yr-old man who complained of abdominal pain was found to have an adenocarcinoma arising in Meckel's diverticulum, as preoperatively diagnosed with 99mTc-pertechnetate scintigraphy. Angiography of the superior mesenteric artery revealed multiple branched arteries and tumor stain, but the vitelline artery was not clearly identified. Surgery revealed that the tumor had invaded the urinary bladder and the ileum, including the diverticulum, and the bladder had to be partially resected. Histopathological examination of the lesion revealed a diverticulum containing normal small bowel mucosa, ectopic normal gastric tissue, and adenocarcinoma. In a review of 30 cases of adenocarcinoma in Meckel's diverticulum in the English and Japanese literature, our case was the first to be diagnosed preoperatively. PMID- 1615951 TI - Tuberous sclerosis complex: review of the gastrointestinal manifestations and report of an unusual case. AB - Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that can affect any organ of the body. We report the first case of advanced colonic adenocarcinoma in a patient with well-documented TSC, offer rationales for the association of this lesion with TSC, and review the literature pertaining to gastrointestinal involvement of this complex. PMID- 1615952 TI - MEGX: from bench to bedside. PMID- 1615953 TI - Beta-blockers in portal hypertension: variation on a theme. PMID- 1615954 TI - Application of the medical decision-making model to esophageal reflux disease: commentary on a study by Breumelhof and Smout. PMID- 1615955 TI - Enteral feeding: PEG or nasoenteric. PMID- 1615956 TI - Clinical application of the study on sphincter of Oddi motor activity in patients with anomalous pancreaticobiliary junction. PMID- 1615957 TI - Hidradenitis suppurativa and Crohn's disease in two families: a significant association? PMID- 1615958 TI - Long-term microscopic findings after colon esophagoplasty. PMID- 1615959 TI - Esophageal tuberculosis. PMID- 1615960 TI - A case of constitutional indocyanine green excretory defect with abnormal retention of sulfobromophthalein: a new functional disorder? PMID- 1615961 TI - Lack of tumor response to interferon in a malignant ECL cell carcinoid of the stomach. PMID- 1615962 TI - Hematoma of the liver caused by self-inflicted trauma mimicking hepatic abscess. PMID- 1615963 TI - Association of intrahepatic portal venous obstruction with intrahepatic calculi formation. PMID- 1615964 TI - Pseudoterranova decipiens larva infection mimicking a chronic peptic ulcer. PMID- 1615965 TI - Folly, woodenheadedness, and the alluvial mind. PMID- 1615966 TI - Therapeutic donor insemination: a prospective randomized trial of fresh versus frozen sperm. AB - OBJECTIVE: We evaluated the efficacy of fresh versus frozen sperm in therapeutic donor insemination. STUDY DESIGN: Fifty-seven women underwent 72 courses of treatment (a maximum of six therapeutic donor insemination cycles--three fresh and three frozen) totaling 198 cycles. Each woman served as her own control and was prospectively randomized to receive a single, timed insemination of either fresh or frozen sperm. RESULTS: Fecundity was 20.6% for fresh sperm cycles and 9.4% for frozen (p less than 0.03, by chi 2 analysis). Fresh cervical cap insemination fecundity was 20.3%; frozen was 7.8% (p less than 0.03, by chi 2 analysis). Fresh intrauterine insemination fecundity was 21.2%; frozen was 15.8% (p = 0.63, by chi 2 analysis). Fresh 3-month life-table pregnancy rates were 48% +/- 10%; frozen rates were 22% +/- 8% (p = 0.05 by Breslow analysis). Survival analysis with fixed covariates showed a positive association with the use of fresh sperm (p = 0.04). CONCLUSION: Cycle fecundity was significantly greater with fresh sperm in women undergoing cervical cap insemination or intrauterine insemination and in women undergoing only cervical cap insemination. These results have important implications for contemporary management of patients undergoing therapeutic donor insemination with frozen sperm. PMID- 1615967 TI - Effect of controlled ovarian hyperstimulation on pregnancy rates after intrauterine insemination. AB - OBJECTIVE: Our objective was to evaluate the effect of controlled ovarian hyperstimulation on pregnancy rates after intrauterine insemination of washed husband's sperm. STUDY DESIGN: In a private practice setting at the Infertility, Gynecology, and Obstetrics Medical Group in San Diego, 79 treatment programs included intrauterine insemination during natural cycles, 195 included clomiphene stimulation, and 53 had human menopausal gonadotropin stimulation. Pregnancy rates and monthly fecundabilities were calculated by life-table analysis and compared by the Z test. RESULTS: By life-table analysis the cumulative probability of pregnancy after intrauterine insemination with no ovulation induction is 21.0% after six cycles with a monthly fecundability of 3.4%. With clomiphene the pregnancy rate is 32.7% with a monthly fecundability of 6.1%, and with human menopausal gonadotropin the pregnancy rate is 60.7% with a monthly fecundability of 13.0%. The human menopausal gonadotropin group had a significantly higher pregnancy rate and monthly fecundability as compared with the other two groups. There were no differences between the no-stimulation and the clomiphene groups. CONCLUSIONS: Human menopausal gonadotropin stimulation results in a significantly higher pregnancy rate and monthly fecundability after intrauterine insemination as compared with no stimulation or clomiphene use. PMID- 1615968 TI - Percutaneous umbilical blood sampling: results from a multicenter collaborative registry. The Western Collaborative Perinatal Group. AB - Percutaneous umbilical blood sampling has become an important diagnostic tool in the evaluation of fetal health. Although recent reports have established the safety of this procedure, most have arisen from single centers with extensive experience. The Western Perinatal Collaborative Group has maintained a continuous registry of percutaneous umbilical blood sampling performed at the 13 member institutions for the years 1986 through 1990. During this period 302 procedures were performed. Primary indications for percutaneous umbilical blood sampling included Rh and non-Rh isoimmunization, intrauterine growth retardation, nonimmune hydrops, fetal anomalies, immune thrombocytopenia purpura, and rapid fetal chromosome analysis. Percutaneous umbilical blood sampling was successfully performed in 93.7% of cases with a sample withdrawn by a single puncture in 80.5% of attempts. In the majority of cases a 22-gauge needle was used. Postprocedural fetal death resulted in six cases (2.1%) and was most often associated with fetal anomalies or an abnormal karyotype. In conclusion, evaluation of the fetal state by percutaneous umbilical blood sampling is a safe and easily performed procedure, as demonstrated by a collaborative multicenter study. PMID- 1615969 TI - Hysteroscopic myometrial biopsy: its use in diagnosing adenomyosis and its clinical application. AB - OBJECTIVE: The purpose of this study was to develop and clinically evaluate a hysteroscopic myometrial biopsy for diagnosing adenomyosis. STUDY DESIGN: Ninety patients with menorrhagia had myometrial biopsies. The depth of adenomyosis was correlated with the severity of menorrhagia. RESULTS: Of the 90 patients studied, 50 had hysteroscopically normal appearing cavities (i.e., without polyps or submucous myomas). Of those 50, 33 (66%) had significant adenomyosis (greater than 1 mm) as compared with controls (0.8 mm). A statistically significant correlation between the depth of adenomyosis and the severity of menorrhagia was found, (p = 0.05). CONCLUSION: A myometrial biopsy can diagnose adenomyosis. Minimal adenomyosis can be treated definitively by endometrial ablation. Deep adenomyosis should be treated with a hysterectomy. Endometrial glands left under a scar could not only bleed and cause pain but also have malignancy potential. The scar may delay bleeding and the diagnosis of endometrial cancer. Routine myometrial biopsy at the time of operative hysteroscopy should be added to our diagnostic armamentarium. PMID- 1615970 TI - Neonatal morbidity according to gestational age and birth weight from five tertiary care centers in the United States, 1983 through 1986. AB - OBJECTIVES: This study details the incidence, by gestational age and birth weight, of specific neonatal morbidities in singleton neonates without major congenital anomalies. STUDY DESIGN: Data were prospectively collected on all deliveries at five tertiary centers in the United States during the years 1983 through 1986. Pregnancies were meticulously dated and the gestational ages of the neonates at delivery were confirmed by Dubowitz score. RESULTS: The incidence of respiratory distress syndrome gradually decreases with increasing gestational age until 36 weeks. A marked decrease in the incidence of necrotizing enterocolitis, patent ductus arteriosus, intraventricular hemorrhage, and sepsis occurs after 32 completed weeks. The number of days of mechanical ventilation for respiratory distress syndrome and newborn stay in the tertiary care facility also were significantly reduced after 32 weeks. CONCLUSIONS: The incidence of both respiratory distress syndrome and patent ductus arteriosus is markedly decreased by both increasing gestational age and birth weight. The incidence of grade III and IV intraventricular hemorrhage, necrotizing enterocolitis, and sepsis virtually vanishes after 34 weeks. These data relating neonatal morbidities to gestational age are important to the obstetrician in the critical decision regarding the timing of delivery and to the parents, who can benefit from a realistic prediction of the neonatal course. PMID- 1615971 TI - Deoxyribonucleic acid analysis by flow cytometry of uterine leiomyosarcomas and smooth muscle tumors of uncertain malignant potential. AB - OBJECTIVES: The histologic distinction of uterine benign leiomyomas from leiomyosarcomas is difficult. Ploidy analysis and measurement of the proliferative rate were examined to determine if they could distinguish malignant from benign tumors and if they were independent prognostic factors. STUDY DESIGN: Paraffin-embedded blocks were recut and prepared for flow cytometry with the technique of Hedley. Mitotic counts and tumor grading were performed on an adjacent hematoxylin and eosin-stained section. Statistical analysis was carried out with chi 2 life-table, and Cox model analysis. RESULTS: There were 33 patients with deoxyribonucleic acid histograms that were acceptable for analysis. Fourteen tumors were diploid and 19 were aneuploid. There were no significant differences in the clinical characteristics between the patients with diploid tumors and those with aneuploid tumors. Aneuploid tumors were more likely to have cellular atypia (p = 0.085). There was a strong correlation between the percentage of cells in the S phase and the mitotic count (p = 0.0001). Increasing mitotic count, increasing S phase, presence of extrauterine disease, and postmenopausal status were all adverse prognostic factors. However, when multivariant analysis with a Cox model was used, only S phase and presence of extrauterine disease were adverse factors. Diploid tumors have a better overall survival (p = 0.0658) but a similar disease-free survival. In those patients who ultimately have relapses, diploid tumors have a significantly longer interval from relapse to death (p = 0.0045). CONCLUSIONS: Neither ploidy analysis nor measurement of the proliferative rate will distinguish a benign from a malignant course in an individual patient; however, ploidy is predictive of survival from time of disease progression and proliferative rate is the strongest predictor of overall survival. The time-proven reliability of mitotic count in the diagnosis of smooth muscle tumors reflects its ability to predict proliferative rate. PMID- 1615972 TI - The utility of immunocytochemistry in invasive adenocarcinoma of the cervix. AB - OBJECTIVES: The purpose of the study was to evaluate the utility of immunocytochemistry in the management of cervical adenocarcinoma. Patterns of reactivity to various immunocytochemical markers were correlated with clinically known risk factors for recurrence. STUDY DESIGN: A retrospective evaluation of 55 patients with invasive cervical adenocarcinoma was conducted. Monoclonal antibodies were generated against various human intermediate filament proteins and tested on fixed, paraffin-embedded tissue by the avidin-biotin complex immunoperoxidase method. Dako V9 antivimentin antibodies and two anticytokeratin antibodies, 35 beta H11 and 34 beta E12, were used. Polyclonal antibodies to carcinoembryonic antigen and antibodies to epithelial membrane antigen were used. RESULTS: Of 55 patients, 50 (91%) had positive epithelial membrane antigen antibodies in tumor cells. Tissue from patients with cervical adenocarcinoma demonstrated positivity for 35 beta H11 antibodies in 46 of 53 patients (87%) and positivity for 34 beta E12 antibodies in 15 of 54 patients (28%). Vimentin antibodies were negative in all except one patient. Carcinoembryonic antigen positive antibodies were detected in 37 of 55 patients (67%). This study also demonstrated consistent negative expression of vimentin in invasive cervical adenocarcinoma. Carcinoembryonic antigen expression rates were 50% and 75% for patients with small tumors (less than or equal to 2 cm) and large tumors (greater than 2 cm), respectively (p less than 0.01). Patients with carcinoembryonic antigen expression are at increased risk for recurrence and also sustain reduced survival potential. CONCLUSIONS: Patients with cervical adenocarcinoma and carcinoembryonic antigen expression are at increased risk for recurrence. We speculate that immunocytochemistry may detect lymph node micrometastases otherwise unsuspected by conventional microscopy. PMID- 1615973 TI - Advanced epithelial ovarian carcinoma: long-term survival experience at the community hospital. AB - OBJECTIVE: The purpose of this study was to determine prognostic factors that could be altered to increase survival of patients with advanced ovarian cancer treated at the community hospital. STUDY DESIGN: This study is a retrospective analysis of 101 patients with stage III and IV epithelial ovarian carcinoma who underwent primary surgery at two private hospitals from 1970 to 1990. RESULTS: Primary laparotomy was done by a general surgeon in 54 cases. The tumors in 23% of stage IIIC cases were debulked to less than or equal to 2 cm residuum. The survival rate decreased as stage or postoperative tumor residual increased. Patients with stage IIIA and IIIB disease had similar survival rates, significantly better than those with stage IIIC disease. Cytoreduction of stages IIIB and IIIC to microscopic disease resulted in a survival curve equal to the "natural optimal" stage IIIA. Patients with cytoreduction of stage IIIC disease to less than or equal to 2 cm did not obtain survival rates equal to those with stage IIIB disease with visible tumor remaining. Patients with stage IIIC disease achieved a significant increase in survival rate if their tumors were cytoreduced to microscopic disease. Platinum-based combination chemotherapy compared with alkylating agents improved survival in patients with stage IIIC disease who had greater than 2 cm tumor residual. Seven patients survived greater than 5 years, with three patients currently free of disease. Three prognostic categories predict decreasing survival: (1) stage IIIC if tumor is cytoreduced to no visible residual, stage IIIA or stage IIIB; (2) stage IIIC with visible tumor residual; (3) stage IV. CONCLUSION: Survival of community hospital-treated advanced ovarian carcinoma patients can be improved by early diagnosis, adjuvant platinum-based combination chemotherapy, and surgical cytoreduction to minimal disease. This treatment requires a team approach and education of the medical staff, including nongynecologists. PMID- 1615974 TI - Modified retropubic cystourethropexy. II. AB - In 1986 we published a preliminary report describing a modification for bladder neck suspension in the treatment of urinary stress incontinence. From 1982 through 1989 135 surgical procedures were performed. Long-term follow-up of these patients is now presented. Of the 135 patients in this study, 118 were available for follow-up at the time of this report; 108 (91.5%) of the 118 reported no urinary leakage. Of the 10 patients who reported continued urinary leakage, only 2 had persistent or recurrent urinary stress incontinence; they were reoperated on with favorable results. The other eight patients reporting urinary leakage were patients with mixed-cause urgency incontinence. The adjusted success rate for the treatment of genuine stress incontinence was therefore 98%. PMID- 1615975 TI - The physiologic mechanisms of variable decelerations. AB - OBJECTIVES: The purpose of this study was to determine the cause and physiologic consequences of variable decelerations. STUDY DESIGN: Previous studies of heart rate changes in human and experimental animals were critically reviewed with respect to the autonomic nervous system component, the cause of the increased vagal activity, and the role of cord compression or other stimuli in these heart rate changes. RESULTS: There is abundant evidence from experimental and human studies that variable decelerations can be reproduced by either cord compression or head compression. The vagal reflex produced is probably caused by a combination of chemoreflex (earlier in the deceleration) and baroreflex (later). The variable deceleration is accompanied by an acidosis, primarily respiratory, and probably hypoxemia. Cord compression results in decreased umbilical blood flow. CONCLUSIONS: Recent Doppler velocimetry studies suggest that even though the variable decelerations may be similar in duration and depth, the reduction of umbilical blood flow may be greater when the prime cause is cord compression than when the prime cause is vagal reflex from another source. PMID- 1615976 TI - Elective induction versus spontaneous labor: a retrospective study of complications and outcome. AB - OBJECTIVE: This retrospective study was undertaken to identify whether electively induced labor places the mother or her fetus at increased risk as compared with her spontaneous labor cohort. STUDY DESIGN: This study compares the labor, delivery, and fetal outcome of 253 parturients in which labor was electively induced with 253 matched controls who began labor spontaneously. All patients were delivered at Huntington Memorial Hospital in Pasadena, California, during the calendar year 1990. The patients were between 37 and 41 weeks' gestation and had no medical or obstetric conditions necessitating induction. The cases and controls were matched for age group, parity, gestational age, and delivering obstetrician. RESULTS: Epidural anesthesia was used in 83.8% of patients in the induction group versus 55.7% in the spontaneous group. Patients with labor induced had a shorter first stage of labor. Meconium staining was found significantly more often in the spontaneous group than in the induced group (16.2% vs 6.7%). This contributed to a greater rate of neonatal consultations in the spontaneous labor group. Although cesarean section rates between the two groups were similar, nulliparous patients in the induction group with an estimated Bishop score of less than or equal to 5 had a 50% cesarean section rate. Iatrogenic prematurity was not encountered. No differences existed between the two groups with respect to intrapartum maternal complications, fetal complications, or postpartum complications. CONCLUSIONS: When compared with spontaneous labor, elective induction of labor at term does not appear to pose an increased risk to the mother or her fetus in a carefully selected patient population. However, elective induction of labor in a nulliparous patient with an unfavorable cervix should be discouraged. PMID- 1615977 TI - Tubal sterilization and risk of subsequent hospital admission for menstrual disorders. AB - OBJECTIVE: Our objective was to investigate tubal sterilization and subsequent hospitalization for menstrual disorders. STUDY DESIGN: Automated discharge data were used in a population-based cohort study of 7253 women aged 20 to 49 years with tubal sterilization (1968 through 1983) at Group Health Cooperative of Puget Sound. Comparisons were with an age-matched cohort of 25,448 nonsterilized women and a nonmatched cohort of 5283 spouses of men with vasectomies. RESULTS: In the sterilization cohort, 282 had hospitalization for menstrual disorders (curettage, n = 191; hysterectomy, n = 66; nonsurgical, n = 25). Risk of hospitalization for menstrual disorders was 2.4 times greater after tubal sterilization (95% confidence interval 2.0 to 2.9). This risk was 6.1 times greater for sterilized women aged 20 to 24 years (95% confidence interval 0.72 to 3.2). Compared with the risk for nonsterilized women whose spouses had a vasectomy, the risk was 1.6 times greater (95% confidence interval 1.3 to 2.1). Hospitalization for menstrual disorders was not more common after unipolar sterilization than after other methods, as might have been expected if the menstrual disorder was related to impaired uteroovarian circulation. CONCLUSIONS: Tubal sterilization is associated with a greater risk of hospitalization for menstrual disorders. A biologic association is not supported by these results. PMID- 1615978 TI - Early amniocentesis: outcome, risks, and technical problems at less than or equal to 12.8 weeks. AB - OBJECTIVE: It is the purpose of this report to evaluate our experience with amniocentesis at less than or equal to 12 weeks' gestation. STUDY DESIGN: Medical records of 936 patients at less than or equal to 12.8 weeks' gestation undergoing genetic amniocentesis between Oct. 1, 1986, and June 30, 1990, were evaluated for gestational age, indication, frequency of needle insertion, amniocentesis complications, and pregnancy outcome. RESULTS: There were seven miscarriages within 2 weeks of amniocentesis (0.7%), 21 miscarriages before 28 weeks (2.2%), and four stillbirths or neonatal deaths (0.4%), resulting in a total postprocedural loss rate of 3.4%. There were 26 chromosomally abnormal fetuses (2.8%). The spontaneous abortion rate in ultrasonographically normal pregnancies at less than 14 weeks, not undergoing amniocentesis, has been estimated at 2.1% to 3.2%. CONCLUSION: Amniocentesis at 12 weeks is a viable option for patients desiring earlier prenatal genetic diagnostic information. PMID- 1615979 TI - Suffer the little children. PMID- 1615980 TI - Anatomic aspects of vaginal eversion after hysterectomy. AB - OBJECTIVE: Our aim was to understand how vaginal eversion after hysterectomy differs from other forms of prolapse. STUDY DESIGN: The role of individual structures involved in vaginal support was studied by pelvic dissection of 61 cadavers. Serial cross sections from 13 additional cadavers were examined. RESULTS: The upper third of the vagina (level I) is suspended from the pelvic walls by vertical fibers of the paracolpium, which is a continuation of the cardinal ligament. In the middle third of the vagina (level II) the paracolpium attaches the vagina laterally to the arcus tendineus and fascia of the levator ani muscles. The vagina's lower third fuses with the perineal membrane, levator ani muscles, and perineal body (level III). Dissection reveals that the paracolpium's vertical fibers in level I prevented prolapse of the vaginal apex and vaginal eversion. CONCLUSIONS: The paracolpium in level I forms the critical factor that differentiates vaginal eversion from posthysterectomy cystocele rectocele or enterocele in which the vaginal apex remains well suspended. PMID- 1615981 TI - Receiver-operator characteristic, efficiency analysis, and predictive value of serum progesterone concentration as a test for abnormal gestations. AB - OBJECTIVE: Our objective was to determine if a discriminatory progesterone concentration could be established that confidently predicted abnormal early gestations. STUDY DESIGN: We analyzed differences in progesterone concentrations between normal (n = 40) and abnormal (n = 34) pregnancies during the first 49 days of gestation. The receiver-operator characteristic curve, test efficiency, and predictive value of serum progesterone to discriminate between an abnormal and normal first-trimester gestation were calculated for progesterone concentrations between 5 and 25 ng/ml. RESULTS: Receiver-operator characteristic curve analysis indicated that the best discriminatory progesterone concentration was 10 ng/ml. Test efficiency was maximum between serum progesterone concentration of 9 to 14 ng/ml (80%). When progesterone was less than 10 ng/ml, the predictive value of the abnormal test result was greater than 90%. CONCLUSION: Receiver-operator characteristic analysis, test efficiency, and the predictive value of an abnormal test result suggest that the best progesterone cut off point that predicts abnormal early pregnancies is 10 ng/ml. PMID- 1615982 TI - Prevalence of out-of-phase endometrial biopsy specimens. AB - OBJECTIVE: We attempted to determine the prevalence of out-of-phase endometrial biopsy specimens among fertile and infertile women and women with recurrent pregnancy loss, histologic dating of biopsies was compared with four reference points for expected ovulation. These reference points included last menstrual period, next menstrual period, luteinizing hormone testing, and ultrasonographic documentation of ovulation. STUDY DESIGN: Four hundred eighty-five endometrial biopsies were performed 7 days after documented ovulation-based ultrasonographic evidence for follicle collapse. The histologic dating was referenced to the last menstrual period, next menstrual period, and ultrasonographic documentation of ovulation. One hundred thirty-two of these women also performed urinary luteinizing hormone surge testing before ovulation and serum progesterone determinations. A comparison of the prevalence of out-of-phase biopsy specimens among groups was determined with the chi 2 test and Fisher's exact test. RESULTS: The prevalence of out-of-phase endometrial biopsy specimens ranged from 42% when last menstrual period was used to 26% with next menstrual period, to 21% with luteinizing hormone testing, and to 4% with ultrasonographic documentation of ovulation. Serum progesterone values among women with a diagnosis of out-of-phase biopsy specimens by any of the reference dates progesterone were similar to those with in-phase biopsy specimens. CONCLUSION: The accuracy of histologic endometrial dating was best determined by ultrasonographic monitoring rather than by last menstrual period, next menstrual period, or luteinizing hormone testing in infertile populations and in those with recurrent pregnancy loss. Additionally, because no significant difference in out-of-phase biopsy specimens exists between fertile and infertile patients and recurrent pregnancy loss, those with the role of this procedure is called into question. PMID- 1615983 TI - Drug use or inadequate prenatal care? Adverse pregnancy outcome in an urban setting. AB - OBJECTIVE: This study analyzed the relationships between illicit drug use, low birth weight, adequacy of prenatal care, and perinatal mortality. STUDY DESIGN: Perinatal outcome parameters in 23,926 deliveries between 1983 and 1990 were analyzed. Statistical analysis (chi 2 analysis) was applied for each year of study to separate the effects of inadequate prenatal care from illicit drug use. RESULTS: Patients with drug use had a two to three times higher incidence of low birth weight and perinatal death. Drug use with more than five prenatal visits had a minimal effect on outcome; drug use with inadequate care was associated with a three times higher incidence of perinatal death and low birth weight. CONCLUSION: Adequacy of prenatal care is a marker of "social chaos" and affects outcome more than drug use itself. PMID- 1615984 TI - Eclampsia. VII. Pregnancy outcome after eclampsia and long-term prognosis. AB - OBJECTIVES: Our goal was to report pregnancy outcome and long-term prognosis after eclampsia. STUDY DESIGN: Women whose pregnancies were managed at the E.H. Crump Women's Hospital between August 1977 and April 1989 were studied. A total of 223 women with eclampsia underwent follow-up for an average of 7.2 years. Thirteen had preexisting hypertension and 210 were normotensive (31 were multiparous and 179 were nulliparous). RESULTS: Among these women 23 who were multiparous and 159 who were nulliparous had 366 subsequent pregnancies: 22% of pregnancies were complicated by preeclampsia, 1.9% by eclampsia, and 2.5% by abruptio placentae; 2.7% resulted in perinatal death. Within the nulliparous group, women who had eclampsia before 37 weeks' gestation in the index pregnancy had significantly higher incidences of preeclampsia and poor perinatal outcome in subsequent pregnancies as compared with those who had eclampsia at greater than or equal to 37 weeks' gestation; the highest incidence of obstetric complications occurred in those having eclampsia at less than or equal to 30 weeks. Twenty of the 210 normotensive women (9.5%) had chronic hypertension on follow-up; the highest incidence (17.9%) being in those with eclampsia at less than or equal to 30 weeks and the lowest incidence (4.8%) in those having eclampsia at greater than or equal to 37 weeks. Women with eclampsia who had preeclampsia in subsequent pregnancies had a higher incidence of chronic hypertension as compared with those who were normotensive in subsequent pregnancies (25% vs 2%, p less than 0.0001). Long-term maternal complications included dialysis required in one patient and one case of cardiomyopathy in women with chronic hypertension; there was one maternal death in a women with chronic hypertension. None of the women had evidence of neurologic deficit or seizures during follow-up. CONCLUSIONS: These findings should be used in counseling women who have had eclampsia and are considering future pregnancies. PMID- 1615985 TI - Preoperative and postoperative analysis of site-specific pelvic support defects in 81 women treated with sacrospinous ligament suspension and pelvic reconstruction. AB - OBJECTIVES: The objectives of this study were to identify factors that predict long-term success, defined as the absence of anatomic defects, in women undergoing pelvic reconstruction and to identify which defects most frequently persist or recur. STUDY DESIGN: Eighty-one women treated by sacrospinous ligament suspension and pelvic reconstruction between 1984 and 1990 had site-specific analysis performed preoperatively and at consecutive postoperative visits. The findings at the 6-week postoperative visit and subsequent visits were compared for each of five sites: urethra, bladder, cuff, cul-de-sac, and rectum. RESULTS: The Fisher exact test showed that patients with no support defects at the 6-week visit were less likely to require subsequent repair than patients who had any defect at that visit (p = 0.003). Thirteen patients with subsequent or persistent cystoceles had no bladder repair performed at the time of the study procedure. However, even with repair the bladder was the most likely site for persistence or recurrence. CONCLUSION: Absence of any pelvic support defect at the 6-week postoperative visit is associated with a 3% likelihood that the patient will require subsequent reconstructive surgery within 2 to 5 years. The anterior segment provides the greatest challenge to restoration of normal anatomy. PMID- 1615986 TI - Cervical cytology: a randomized comparison of four sampling methods. AB - OBJECTIVE: The purpose of this study was to compare smear quality and endocervical cell recovery of four cervical smear sampling devices. STUDY DESIGN: Two thousand fifteen patients undergoing routine cervical smears at the University of Tennessee Obstetrics and Gynecology clinics were randomly assigned to a cotton swab-spatula, Cytobrush-spatula, Cervex-Brush, or Bayne Pap Brush. The cytopathology laboratory, blind to method, used specific criteria to grade smears as being optimal, adequate, marginal, or inadequate. Statistical analysis was by the chi 2 and analysis of variance tests. RESULTS: No statistical differences occurred among the groups for nonpregnant patients. For pregnant patients smear quality was improved with both Cytobrush-spatula and Bayne Pap Brush versus cotton swab-spatula (p = 0.0301 and 0.0004, respectively); cotton swab-spatula had fewer endocervical cells than the Cytobrush-spatula (p = 0.0001), Cervex-Brush (p = 0.0288), and Bayne Pap Brush (p = 0.0081). CONCLUSIONS: The cotton swab-spatula and Cytobrush-spatula appear to be the most effective screening methods for nonpregnant and pregnant patients, respectively. PMID- 1615987 TI - Interlaboratory variation in antiphospholipid antibody testing. AB - OBJECTIVE: Because of the widespread use of antiphospholipid antibody testing in the evaluation of patients with recurrent pregnancy loss, we evaluated the consistency of results among laboratories testing for anticardiolipin antibody and the lupus anticoagulant. STUDY DESIGN: A questionnaire regarding methods used and samples of blood from 20 patients were sent to five university-based and five commercial facilities for antiphospholipid antibody testing. RESULTS: The responses of the participating laboratories to the questionnaires revealed significant differences in methods, standardization, and units of reporting. For anticardiolipin antibody, the number of specimens found to be positive for any isotype (immunoglobulin G, M, or A) varied considerably among laboratories, with a range of 5 to 13. All laboratories were in agreement (i.e., at least one isotype was present or all were absent) for only 5 of 20 specimens (25%). In contrast, lupus anticoagulant results were more reproducible, although one facility reported results markedly discordant from the other four laboratories. CONCLUSION: These observations suggest that significant interlaboratory variation exists in antiphospholipid antibody, and particularly anticardiolipin antibody, testing and might lead to unnecessary therapeutic interventions. PMID- 1615988 TI - Reproductive outcome in women with recurrent spontaneous abortions of alloimmune and autoimmune causes: preconception versus postconception treatment. AB - OBJECTIVES: The null hypothesis is that treatment of women with recurrent spontaneous abortions with anticoagulation and immunosuppression will not increase the reproductive outcome if it is started preconceptionally. STUDY DESIGN: Ninety-four women with recurrent spontaneous abortion with autoimmune abnormalities comprised the study group. Group I began autoimmune therapy 48 hours after ovulation: heparin 5000 U twice daily, aspirin 80 mg daily, and prednisone 5 mg twice daily, with an increase to 10 mg twice daily when pregnant. Group II started the same medication after a positive pregnancy test. Group III received no medication. Controls were 19 women with no autoimmune abnormalities. The frequency of reproductive outcome was subject to multiple comparison by the Duncan test. RESULTS: The percentages of live-born children in groups I, II, and III were 74%, 44%, and 11%, respectively. CONCLUSIONS: Preconception diagnostic work-up and treatment of autoimmune abnormalities in women with histories of recurrent spontaneous abortion is advocated. PMID- 1615989 TI - The Green Bay cesarean section study. II. The physician factor as a determinant of cesarean birth rates for failed labor. AB - OBJECTIVE: Our study was designed to develop a profile of specific labor management characteristics generally used by physicians with low versus those with high rates of cesarean sections in the care of nonprogressive labor in nulliparous patients. STUDY DESIGN: A 4-year retrospective data set was used to analyze all patients with nonprogressive labor cared for by 11 board-certified obstetricians and gynecologists practicing full-time at two Green Bay hospitals. Variations in labor management are analyzed and tested for their effect on the rate of cesarean section for failure of labor to progress. RESULTS: Cesarean section in nulliparous women for nonprogressive labor varied from 4.3% of all deliveries in the low group to 12.3% in the high group. Through multivariate analysis we developed a profile of specific labor management characteristics used by physicians with low versus those with high rates of cesarean section. CONCLUSION: These techniques can be used to definitively identify management strategies that result in a decrease in cesarean rates for nonprogressive labor. PMID- 1615990 TI - Vaginal birth after cesarean delivery: are there useful and valid predictors of success or failure? AB - OBJECTIVE: Before parturition are there useful and valid predictors of successful or unsuccessful vaginal birth after previous cesarean birth that could be used to enhance the obstetric care of a patient and her pregnancy? STUDY DESIGN: The clinical course and outcome of all patients who attempted vaginal birth after cesarean delivery at one level III center during 1989 were evaluated to identify factors prognostic of a successful or unsuccessful patient group; use of this information in stepwise logistic regression and cluster analysis was disappointing. RESULTS: No single criterion or optimal clusters of factors were found and no equation achieved greater than 75% predictability of outcome with acceptable sensitivity and specificity. CONCLUSIONS: Before parturition prediction of outcome of vaginal birth after cesarean delivery is tenuous regardless of past obstetric history or recent clinical parameters. Thus it seems appropriate to encourage a trial of labor in almost all patients with a prior low segment uterine incision (transverse or vertical) unless there is a strong physician or patient-derived contraindication to such an undertaking. PMID- 1615991 TI - Comparison of dynamic image and pulsed Doppler ultrasonography for the diagnosis of the small-for-gestational-age fetus. AB - OBJECTIVE: Because poor fetal growth is a significant cause of perinatal morbidity and mortality, a prospective study was undertaken to evaluate the ability of real-time ultrasonography and Doppler velocimetry to detect the small for-gestational-age fetus. STUDY DESIGN: A prospective study of 136 women at risk for fetal growth abnormalities was conducted. Patients were delivered within 3 weeks and had live-born, nonanomalous, singleton infants. The relative estimated fetal weight (estimated fetal weight divided by the median birth weight for gestational age) and the systolic/diastolic ratio were measured and compared with receiver-operator characteristic curves. In this method the area under the curve is the index of performance. RESULTS: Forty-six infants were small for gestational age. Although both relative estimated fetal weight (area under the curve = 0.923) and systolic/diastolic ratio (area under the curve = 0.837) were significantly associated with the small for gestational age fetus, the former was more strongly correlated, p = 0.021. CONCLUSION: Relative estimated weight is more sensitive and specific and should be the preferred parameter when gestational age is known. PMID- 1615992 TI - Prediction of respiratory distress syndrome by a new colorimetric assay. AB - OBJECTIVE: The purpose of this study was to evaluate the clinical performance of a new, simple, and rapid colorimetric assay for predicting respiratory distress syndrome. STUDY DESIGN: Ninety-four specimens obtained within 3 days of delivery were assayed with the new test. For 78 of these specimens, the lecithin/sphingomyelin ratio was also determined. Significant differences were calculated with chi 2 analysis. Cutoff points were selected by maximizing the corresponding sums of sensitivity and specificity and from receiver-operator characteristic curves. RESULTS: The specificity of the new colorimetric test was better than 89%, and it yielded more than 86% correct diagnoses. Furthermore, the test had a significantly (p less than 0.05) lower percentage of false-immature results than that obtained with the lecithin/sphingomyelin ratio. Moreover, the new test performed relatively well in analyses of patients between 27 weeks and 36 weeks' gestation. CONCLUSION: We concluded that the new assay is reliable and that it can serve as a useful alternative to current methods for predicting respiratory distress syndrome. PMID- 1615993 TI - Urinary incontinence: correlation of history and brief office evaluation with multichannel urodynamic testing. AB - OBJECTIVE: Patients' histories of urinary incontinence and the results of several standard clinical tests were correlated with final diagnoses obtained by multichannel urodynamic testing. We used a combination of clinical test results to predict the final diagnoses. STUDY DESIGN: Ninety consecutive women with a primary complaint of urinary incontinence completed a standardized questionnaire and underwent a structured clinical examination consisting of several standard clinical tests. Each patient later underwent multichannel urodynamic testing to obtain a final diagnosis. RESULTS: Although the symptoms of stress incontinence were significantly associated with genuine stress incontinence and mixed incontinence, overlap in patients with detrusor instability did not allow the histories to be useful diagnostically. The only clinical tests showing significant association with the final diagnoses of incontinence were the cough stress test and single-channel medium-fill cystometry. Reliable prediction of the urodynamic diagnosis of incontinence could not be achieved with either of these two tests or with a combination of variables obtained by discriminant analysis. CONCLUSIONS: Women with complaints of urinary incontinence, especially those for whom surgery is contemplated, should undergo complete urodynamic evaluation when it is available. PMID- 1615994 TI - Mechanism of recurrent spontaneous abortion. I. Ultrasonographic findings. AB - OBJECTIVES: Our objective was to study the mechanisms of early pregnancy loss with ultrasonographic findings in pregnancies that terminated in repeat abortion in women with recurrent spontaneous abortion compared with patients with spontaneous abortion with no previous spontaneous abortion and with women with recurrent spontaneous abortion who had viable pregnancies. STUDY DESIGN: A prospective, unselected study of 83 pregnancies followed from 4 to 12 weeks of gestation. Weekly transvaginal ultrasonography.among 43 pregnancies terminating in abortion were compared with 40 pregnancies ending in live birth with the Fisher exact test with a p value of significance assigned at less than 0.05. RESULT: A significant difference in the presence of fetal heart activity was observed at 6 weeks +/- 5 days among women who subsequently aborted when recurrent spontaneous abortions were compared with no history of abortion (55% and 14%, p less than 0.02). Fetal pole size was small in 86% of pregnancies lost after fetal heart activity. CONCLUSION: Ultrasonographic examination at 6 weeks can diagnose impending abortion with a sensitivity of 85%, specificity of 93%, positive predictive value of 92%, and negative predictive value of 87% among women with recurrent spontaneous abortion. PMID- 1615995 TI - Acute childbirth morbidity: its measurement using hospital charges. AB - OBJECTIVES: An analytic descriptive analysis of acute childbirth morbidity was carried out at Duke University Medical Center, comparing patients delivered by primary cesarean section with those delivered vaginally. STUDY DESIGN: All primary cesarean deliveries and vaginal deliveries from July 1, 1981, through June 30, 1986, were combined with maternal and infant charge data. A total of 7256 patients were analyzed. A description of the charges for the associated diagnoses was carried out. A morbidity index was used to identify differences in predicted median hospital charges with 95% confidence intervals. RESULTS: The ratio of mean primary cesarean delivery to mean vaginal delivery total charges was 2.5:1. The magnitude of the mean hospital charges was inversely related to the frequency of the indication with the lowest charges associated with dystocia and the highest with multiple pregnancy. Antepartum risk factors (increased maternal age, patient referral) were associated with increases in maternal and infant morbidity as measured by the morbidity index. Chronic maternal hypertension resulted in decreased maternal morbidity but increased infant morbidity when primary cesarean delivery was used. Although preterm delivery was associated with large increases in charges, it was not significantly altered by using primary cesarean delivery. Risk factors associated with the management of abnormalities of labor were associated with decreases in maternal and infant morbidity when primary cesarean delivery was used. CONCLUSION: Analysis of acute childbirth morbidity, as measured by hospital charges, showed marked variation of diagnosis and risk-specific charges for patients delivered by primary cesarean section. PMID- 1615996 TI - Treatment of fetal supraventricular tachycardia with flecainide acetate after digoxin failure. PMID- 1615997 TI - Amniotic fluid glucose and intraamniotic infection: sensitivity, specificity, and predictive values. PMID- 1615998 TI - Ureaplasma urealyticum resistance to erythromycin: confirmed by clinical trial. PMID- 1615999 TI - Steroids receptors in the endometrium during clomiphene citrate treatment. PMID- 1616000 TI - The tip of the iceberg and the best fit in ultrasonographic dating of pregnancy. PMID- 1616001 TI - Hydroxyurea and pregnancy. PMID- 1616002 TI - Gangliosides as modulators of cell function. AB - Gangliosides, sialic acid-containing glycosphingolipids, are found in the outer leaflet of the plasma membrane of all vertebrate tissues and species. This report presents a brief introduction to the gangliosides and reviews the chemistry and topography of their biosynthesis. It also presents an overview of the present evidence supporting a physiological significance for the gangliosides in a variety of experimental systems. This includes consideration of their potential roles in development and cell adhesion. In addition, experimental examples in which gangliosides appear to influence signal transduction processes through their interactions with plasma membrane proteins are discussed. PMID- 1616003 TI - Ca2+/calmodulin regulation of putrescine uptake in cultured gastrointestinal epithelial cells. AB - Regulation of putrescine uptake in a small intestinal crypt cell line, IEC-6 cells, was examined. Uptake of [14C]putrescine was measured throughout a normal growth curve and was found to be inversely related to growth. Kinetic analysis at low and high cell density revealed the inhibition of uptake in confluent cells was due to a five-fold reduction in Vmax of uptake, 199.5 vs. 43.1 pmol.10(5) cells-1.h-1, respectively. Three gastrointestinal hormones, gastrin, secretin, and cholecystokinin, produced partial inhibition of [14C]putrescine uptake. Conversely, treatment of quiescent cells with 5% fetal bovine serum to stimulate growth did not affect uptake. Influence of putrescine uptake on free ionized intracellular Ca2+ ([Ca2+]i) was measured by microspectrofluorometry using the Ca(2+)-sensitive fluoroprobe fura-2. Basal [Ca2+]i was calculated to be 112 nM and increased rapidly to 313 nM upon addition of 10 microM putrescine. Preventing the rise in [Ca2+]i using an intracellular Ca2+ buffer, 1,2-bis(2 aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester, decreased [14C]putrescine uptake to 29.5 +/- 5.3% of control values. 45Ca2+ flux experiments and measurement of transport in 0 Ca2+ and 0.5 mM EDTA suggested an intracellular source of calcium was mobilized during putrescine uptake. Finally, use of the putative calmodulin antagonist N-(6-aminohexyl)-5-chloro-l naphthalenesulfonamide caused a dose-dependent inhibition of [14C]putrescine uptake with 50% inhibitory concentration of approximately 7 microM. These data suggest that putrescine uptake in IEC-6 cells may be regulated by a Ca2+/calmodulin-dependent mechanism. PMID- 1616004 TI - Norepinephrine-induced phosphatidylcholine hydrolysis by phospholipases D and C in rat tail artery. AB - Rat tail arterial segments were incubated with [3H]choline to selectively label endogenous phosphatidylcholine. Norepinephrine (NE; 10(-5) M) addition for periods of 10 s to 30 min significantly increased the concentration of extracellular phosphatidylcholine metabolites, [3H]choline, and [3H]phosphocholine. The release of [3H]choline and [3H]phosphocholine from the segments was NE dose dependent (10(-6)-10(-3) M). NE also increased the formation of [3H]phosphatidylethanol in [3H]myristate-labeled tail artery in the presence of ethanol, characteristic of phospholipase D activity. NE-induced phosphatidylcholine hydrolysis was blocked by pretreatment with prazosin (10(-5) M) and was unchanged by pretreatment with propranolol (10(-5) M). 4 beta-phorbol 12,13-dibutyrate (PDBu, 10(-6) M) stimulated the release of [3H]choline, which was inhibited by pretreatment with staurosporine (10(-5) M). The stimulatory effect of NE on phosphatidylcholine metabolism was not altered by either pretreatment with staurosporine (10(-5) M) or calcium-free buffer. In summary, we have demonstrated NE-stimulated phosphatidylcholine hydrolysis by phospholipase D and C in intact vascular smooth muscle. This effect of NE was dose dependent and was mediated through the alpha 1-adrenergic receptor. Norepinephrine and PDBu stimulated phosphatidylcholine hydrolysis through different mechanism(s), and the stimulatory effect of NE did not seem to require protein kinase C and calcium influx. PMID- 1616005 TI - Differential sensitivity of AS-30D rat hepatoma cells and normal hepatocytes to anoxic cell damage. AB - A substantial fraction of cells present within hard tumors experience extremely hypoxic and hypoglycemic conditions that can lead to phenotypic alterations such as increased metastatic potential and chemotherapeutic drug resistance. Little is known regarding the influence of anoxic aglycemia on tumor cell energy metabolism and viability, and no direct comparisons have been made between the effects of this form of metabolic stress on tumor cells and their tissue of origin. In this study, the effects of in vitro aglycemic incubation under N2 (with or without iodoacetate) on trypan blue exclusion, lactate dehydrogenase release, cell surface blebbing, ATP levels, and mitochondrial respiratory capacity of rat AS 30D ascites hepatoma cells and normal hepatocytes were measured. Under anoxic aglycemic conditions, the period of incubation during which 50% viability was lost was 2 h for hepatocytes and 6-8 h for AS-30D cells. In contrast, the rate of anoxia-induced loss of ATP was comparable for the two cell types, and mitochondrial damage was actually accelerated in the tumor cells. These findings suggest that tumor cells are more resistant to anoxic cell death because of their greater ability to withstand deenergization and subcellular injury. PMID- 1616006 TI - Secretion of K and Cl across colonic epithelium: cellular localization using electron microprobe analysis. AB - Electron microprobe analysis of quick-frozen distal colonic epithelium from guinea pig was used to locate the cells responding to secretory stimuli. Concentrations of Na, K, and Cl were similar for cells of surface and crypt in the unstimulated state, 8, 149, and 46 mmol/kg wet weight, respectively. Stimulation of either K and Cl secretion with prostaglandin E2 or K secretion alone with epinephrine increased Na to approximately 12 mmol/kg wet weight in crypt cells but not in surface cells or cells in the crypt neck. This result supports the location of ion secretory cells in the lower two-thirds of the crypt. In the vacuoles of crypt columnar cells, stimulation of KCl secretion decreased K, S, Mg, and Ca and increased Na and Cl, indicative of the concomitant release of vacuole contents. Mucin granules in crypt goblet cells contained more S and Mg than granules in surface goblet cells. These findings support the concept of differentiation in ion and macromolecular secretory function along the axis from crypt to surface epithelium. PMID- 1616007 TI - Epithelial permeability factor: a serum protein that condenses actin and opens tight junctions. AB - An epithelial permeability factor (EPF) in human serum lowered, within 1 h, the transepithelial electrical resistance and opened the tight junctions of a cultured kidney epithelium (Madin-Darby canine kidney) when it came in contact with the basolateral surface of the kidney epithelium. Size-exclusion chromatography of serum or heat-inactivated serum resolved seven peaks of EPF activity (approximately 15, approximately 30, approximately 45, approximately 60, approximately 120, and approximately 240 kDa and greater than 240 kDa) with 65% of the activity at approximately 45, approximately 60, and approximately 120 kDa. Heat inactivation, which had no effect on total activity, caused a significant decrease in the activity at 120 kDa and an equivalent rise in activity at 45 kDa. Although acid charcoal extraction or lectin affinity chromatography did not remove activity, EPF activity was eliminated by pepsin. Heat-inactivated serum or fractions containing EPF had no effect on ZO-1 localization but did cause a dose dependent focal condensation of the perijunctional actin ring at sites where three or more cells were in contact. These data suggest that EPF is a protein that appears to form multimers that interact with the basolateral surface of the epithelium and cause constriction of the cytoskeleton and an increase in permeability at specific sites along the tight junction. PMID- 1616008 TI - Flow-induced calcium transients in single endothelial cells: spatial and temporal analysis. AB - Endothelial cells (EC) are uniquely situated to respond to hemodynamic forces. Because flow-mediated release of endothelial-derived relaxing factors is associated with increased EC intracellular calcium ([Ca2+]i), we sought to determine the effects of fluid shear stress on EC [Ca2+]i. Cells were subjected to flow in parallel-plate flow chambers and glass capillary tubes, and single cell [Ca2+]i was measured using fura-2. Upon initiation of flow (shear stress of 30 dyn/cm2), [Ca2+]i increased within 30 s to a peak value (approximately 4 times basal) and then decreased slowly to a plateau (approximately 2 times basal) that persisted for greater than 5 min. A striking finding was that the increases in [Ca2+]i were nonhomogeneous; the nuclear region and a periplasma membrane region were higher than the cytosol. After flow cessation, the increase in [Ca2+]i could be elicited repeatedly by resumption of flow. Removing extracellular Ca2+ did not eliminate the response. In contrast to EC, rat aortic smooth muscle cells showed no flow-mediated increase in [Ca2+]i. The complexity of EC [Ca2+]i response to flow suggests regulation of [Ca2+]i by several mechanisms that may serve a role in both short- and long-term EC responses to flow. PMID- 1616009 TI - Magnetic field influence on acetylcholine release at the neuromuscular junction. AB - The effects of a static magnetic field on the frequency of miniature end-plate potentials (MEPPs), recorded from the murine phrenic nerve-diaphragm preparation, were studied. In the presence of a 1,200-G field, statistically significant changes in MEPP frequency were observed. There was a modest increase in frequency at temperatures at and below 34 degrees C and a prominent decrease in frequency at temperatures above 35 degrees C. This temperature-dependent phenomenon was not seen in the absence of calcium in the perfusate. These results suggest that, at its phase transition temperature, the diamagnetic anisotropy of the presynaptic membrane is sufficient to influence neurotransmitter release by altering the function of the transmembrane calcium transfer mechanism. PMID- 1616010 TI - Maxi K+ channel in apical membrane of vestibular dark cells. AB - Recordings were made on excised apical membrane patches from vestibular dark cells from the semicircular canal of gerbils to determine if ion channels could be involved in the process of K+ secretion. Both nonselective cation channels [Am. J. Physiol. 262 (Cell Physiol. 31): C1430-C1436, 1992] and K(+)-selective channels were found. The K+ channels occurred in only 0.7% of the patches. In symmetrical 145 mM KCl solutions, the current-voltage (I-V) relation of the K(+) selective channel was linear, indicating the absence of rectification, and the conductance was 240 +/- 8 pS (n = 8). The Goldman-Hodgkin-Katz equation for current carried solely by K+ could be fitted to the I-V relation in asymmetrical K+ and Na+ solutions and yielded a K+ permeability of 5.78 x 10(-13) cm3/s (n = 12). The channel was shown to be impermeable to Li+, NH4+, N-methyl-D-glucamine, and Cl-. Channel activity increased with depolarization and with increasing free [Ca2+]; for voltages between +40 and -60 mV, the strongest regulation occurred in the range 10(-6) to 10(-5) M Ca2+. Tetraethylammonium (2 x 10(-2) M) had from the cytosolic side no effect on the open probability (Po) but completely inhibited activity from the extracellular side. Po was reduced by Ba2+ (5 x 10(-3) M), verapamil (10(-4) M), quinine (10(-4) M), and quinidine (10(-4) and 10(-3) M), while lidocaine (5 x 10(-3) M) had no measurable effect on Po but decreased the amplitude. Rb+ and Cs+ were either poorly permeable or partially blocked the channel in a voltage-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616011 TI - Glucocorticoid-induced skeletal muscle atrophy in vitro is attenuated by mechanical stimulation. AB - Glucocorticoids induce rapid atrophy of fast skeletal myofibers in vivo, and either weight lifting or endurance exercise reduces this atrophy by unknown mechanisms. We examined the effects of the synthetic glucocorticoid dexamethasone (Dex) on protein turnover in tissue-cultured avian fast skeletal myofibers and determined whether repetitive mechanical stretch altered the myofiber response to Dex. In static cultures after 3-5 days, 10(-8) M Dex decreased total protein content 42-74%, total protein synthesis rates 38-56%, mean myofiber diameter 35%, myosin heavy chain (MHC) content 86%, MHC synthesis rate 44%, and fibronectin synthesis rate 29%. Repetitive 10% stretch-relaxations of the cultured myofibers for 60 s every 5 min for 3-4 days prevented 52% of the Dex-induced decrease in protein content, 42% of the decrease in total protein synthesis rate, 77% of the decrease in MHC content, 42% of the decrease in MHC synthesis rate, and 67% of the decrease in fibronectin synthesis rate. This in vitro model system will complement in vivo studies in understanding the mechanism by which mechanical activity and glucocorticoids interact to regulate skeletal muscle growth. PMID- 1616012 TI - Muscle fatigue in frog semitendinosus: role of intracellular pH. AB - The purpose of this study was to utilize glass microelectrodes to characterize the intracellular pH (pHi) before and during recovery from fatigue in the frog semitendinosus (ST) muscle. A second objective was to evaluate the relationship between pHi and contractile function. The frog ST muscle (22 degrees C) was fatigued by direct electrical stimulation with 100-ms 150-Hz trains at 1/s for 5 min. Peak tetanic force (Po) was reduced to 8.5% of initial force and recovered in a biphasic manner, returning to the resting value by 40 min. Resting pHi was 7.00 +/- 0.02 (n = 37) and declined with fatigue to an average value of 6.42 at 3 min of recovery. During recovery pHi significantly increased and by 25 min had returned to the prefatigue value. The pHi recovery was highly correlated to the slow phase of Po recovery (r = 0.98, P less than 0.001). The mean resting membrane potential was -78 +/- 1.0 mV (n = 42) and at 3 min of recovery was depolarized to -67 +/- 4 mV. Both the peak rate of twitch force development (+dP/dt) (r = 0.99, P less than 0.001) and decline (-dP/dt) (r = 0.94, P less than 0.014) were highly correlated to pHi during the slow phase of recovery. Contraction time (CT) and one-half relaxation time (1/2RT) increased significantly and recovered exponentially. The recovery of CT and 1/2RT were both significantly correlated to pHi (r = -0.93, P less than 0.001 and r = -0.86, P less than 0.001 for CT and 1/2RT, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616013 TI - Mechanism of heptanol-induced uncoupling of cardiac gap junctions: a perforated patch-clamp study. AB - The influence of heptanol on gap junctional and non-junctional membrane currents was studied in cultured neonatal rat heart cells using both the whole cell and perforated patch voltage-clamp method. With both methods, exposure to heptanol produced a dose-dependent decrease in the junctional current (dissociation constant = 0.54 and 1.20 mM for whole cell and perforated patch experiments, respectively). Heptanol-induced uncoupling was reversible. In the same concentration range, heptanol reduced all nonjunctional membrane ionic currents examined. This suggests that heptanol does not act specifically on gap junction channels but rather on the structure of the lipid membrane. This hypothesis is strengthened by the observation that in monolayer cultures of neonatal rat heart cells fluorescence steady-state anisotropy decreased proportional with increasing the heptanol concentration in the bath. Single-channel conductances (gamma j) were identical with both recording methods (21 and 40-45 pS); heptanol did not alter gamma j. Under conditions of reduced junctional coupling induced by heptanol, junctional conductance (gj) displayed voltage sensitivity at values of gj at which no voltage sensitivity could be observed under control conditions. These results suggest that heptanol-dependent uncoupling was caused by a decrease in open probability of the gap junction channels. PMID- 1616014 TI - Interactions between ANG II, sympathetic nervous system, and baroreceptor reflexes in regulation of blood pressure. AB - The renin-angiotensin system plays an important role in the regulation of arterial blood pressure and in the development of some forms of clinical and experimental hypertension. It is an important blood pressure control system in its own right but also interacts extensively with other blood pressure control systems, including the sympathetic nervous system and the baroreceptor reflexes. Angiotensin (ANG) II exerts several actions on the sympathetic nervous system. These include a central action to increase sympathetic outflow, stimulatory effects on sympathetic ganglia and the adrenal medulla, and actions at sympathetic nerve endings that serve to facilitate sympathetic neurotransmission. ANG II also interacts with baroreceptor reflexes. For example, it acts centrally to modulate the baroreflex control of heart rate, and this accounts for its ability to increase blood pressure without causing a reflex bradycardia. The physiological significance of these actions of ANG II is not fully understood. Most evidence indicates that the actions of ANG to enhance sympathetic activity do not contribute significantly to the pressor response to exogenous ANG II. On the other hand, there is considerable evidence that the actions of endogenous ANG II on the sympathetic nervous system enhance the cardiovascular responses elicited by activation of the sympathetic nervous system. PMID- 1616015 TI - Theory of production rate calculations in steady and non-steady states and its application to glucose metabolism. AB - I present a review and synthesis of the basic theory, steady state, and non steady state for the calculation of metabolite production rates for systems that have a central well-mixed compartment that is the site of tracer input and sampling. The theory is then applied to the calculation of glucose production. If the only inputs are into the central compartment, an experimental design that involves varying tracer infusion rates to maintain constant specific activity in the central compartment and the same constant specific activity in the peripheral compartments allows calculation of the endogenous production. That holds even if the models are unidentifiable. The correct equation and Steele's pool fraction approximation reduce to the same result for this experimental design. However, that does not justify the use of Steele's equation when there are deviations from the exact experimental design. When the specific activity in the central compartment is not constant, model-dependent correction terms to Steele's equation are needed. PMID- 1616016 TI - Oscillations of lactate released from islets of Langerhans: evidence for oscillatory glycolysis in beta-cells. AB - Oscillations in the glycolytic process have been demonstrated in a number of different biological systems. However, their presence has never been demonstrated in insulin-secreting beta-cells. We used lactate as a marker for glycolysis and measured lactate and insulin concentrations in the effluent of isolated perifused rat islets of Langerhans. Sustained regular oscillations in lactate concentrations with an average period of 16-20 min were observed in islets that were perifused with medium containing 5.5 or 16.7 mM glucose. Sustained oscillations of insulin concentrations secreted by the islets were also observed in these experiments, and the average period of oscillation was 14.6 +/- 2.3 min at 16.7 mM glucose. Mean insulin concentrations at 5.5 mM glucose were too low to permit analysis of oscillations. Spectral analysis confirmed the regularity of the lactate and insulin oscillations and showed peaks that were consistent with the average periods obtained using the Clifton program. Moreover, spectral analysis demonstrated marked similarity between the patterns of lactate and insulin oscillation during perifusion with 16.7 mM glucose. Cross-correlation analysis found these oscillations not to be consistently in phase. In conclusion, sustained oscillations in lactate released from islets of Langerhans suggest that the glycolytic process in beta-cells also oscillates. The similarity of the periods of lactate and insulin raises the possibility that oscillations in glycolysis may provide a mechanism for pulsatile insulin secretion. PMID- 1616017 TI - Epinephrine augments cortisol secretion from isolated perfused adrenal glands of guinea pigs. AB - To determine direct effects of epinephrine on adrenal cortisol secretion, bilateral adrenal glands were isolated from guinea pigs, together with bilateral kidneys, aorta, and inferior caval vein for influent and effluent routes. The preparation was perfused with oxygenated Krebs-Ringer bicarbonate solution (pH 7.4) containing 10 mM glucose, 0.2% bovine serum albumin, and 4.6% dextran. The perfusate cortisol level was elevated by the addition of epinephrine in a dose dependent manner at concentrations greater than 100 pg/ml and increased eightfold as high as the basal level at 1 micrograms/ml epinephrine. The stimulatory effect of epinephrine on cortisol secretion was completely abolished by phentolamine, an alpha-adrenergic antagonist but was not affected by propranolol, a beta adrenergic antagonist. These results demonstrate that epinephrine has a direct stimulatory effect on adrenal cortisol secretion via an alpha-adrenergic mechanism and also suggest that not only adrenocorticotropin but also epinephrine is a most important factor for the regulation of cortisol secretion. PMID- 1616018 TI - Effects of infused amino acids on glucose production and utilization in healthy human subjects. AB - Amino acids have been reported to increase endogenous glucose production in normal human subjects during hyperinsulinemia: however, controversy exists as to whether insulin-mediated glucose disposal is inhibited under these conditions. The effect of an amino acid infusion on glucose oxidation rate has so far not been determined. Substrate oxidation rates, endogenous glucose production, and [13C]glucose synthesis from [13C]bicarbonate were measured in six normal human subjects during sequential infusions of exogenous glucose and exogenous glucose with (n = 5) or without (n = 5) exogenous amino acids. Amino acids increased endogenous glucose production by 84% and [13C]glucose synthesis by 235%. Glucose oxidation estimated from indirect calorimetry decreased slightly after amino acids, but glucose oxidation estimated from [13C]glucose-13CO2 data was increased by 14%. It is concluded that gluconeogenesis is the major pathway of amino acid degradation. During amino acid administration, indirect calorimetry underestimates the true rate of glucose oxidation, whereas glucose oxidation calculated from the 13C enrichment of expired CO2 during [U-13C]glucose infusion does not. A slight stimulation of glucose oxidation during amino acid infusion, concomitant with an increased plasma insulin concentration, indicates that amino acids do not inhibit glucose oxidation. PMID- 1616019 TI - Intensity of lactation modulates renal 1 alpha-hydroxylase and serum 1,25(OH)2D in rats. AB - Renal 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase) activity and serum 1,25-dihydroxyvitamin D [1,25(OH)2D] concentration were measured in lactating rats suckling litters of 3, 6, or 12 pups to determine the effect of increasing lactational intensity on the biosynthesis of 1,25(OH)2D. Serum Ca2+, total Ca, Pi, and immunoreactive parathyroid hormone were also determined. The average daily litter weight gain for each litter size was calculated from the gain over the last 4-6 days of each of three experiments and was used as an index of lactational intensity. Highly significant correlation coefficients were found between 1 alpha-hydroxylase and average daily litter weight gain (rs = 0.63, n = 53, P less than 0.001), serum 1,25(OH)2D and average daily litter weight gain (rs = 0.62, n = 50, P less than 0.001), 1 alpha-hydroxylase and serum total Ca (rs = 0.52, n = 53, P less than 0.001), and average daily litter weight gain and total Ca (rs = -0.52, n = 53, P less than 0.001). Neither serum phosphorus nor immunoreactive parathyroid hormone correlated significantly with 1 alpha hydroxylase. In addition, construction of regression models using a stepwise forward variable selection procedure revealed serum total Ca concentration to be a significant predictor for both serum 1,25(OH)2D and renal 1 alpha-hydroxylase in lactating rats. These data support the hypothesis that increasing lactational intensity leads to decreasing serum Ca concentration, resulting in stimulation of 1 alpha-hydroxylase activity and a rise in the serum 1,25(OH)2D level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616020 TI - Effects of short-term testosterone exposure on insulin sensitivity of muscles in female rats. AB - The effects of testosterone on insulin sensitivity were studied in oophorectomized female rats. Euglycemic, hyperinsulinemic clamp measurement showed a marked decrease of insulin sensitivity after 48 but not 24 h of testosterone exposure, which was overcome at high insulin concentrations. Insulin stimulation of 2-deoxyglucose uptake as well as glycogen synthesis was measured in the white and red parts of the gastrocnemius, the extensor digitorum longus, and soleus muscles as well as in the liver (only glycogen synthesis). After 24 h of treatment, inhibition of both 2-deoxyglucose uptake and glycogen synthesis was found in the most insulin-sensitive muscles. After 48 h of insulin stimulation, glycogen synthesis was inhibited in all examined individual muscles (white and red parts of gastrocnemius, extensor digitorum longus, and soleus) as was the activity of the insulin-sensitive part of glycogen synthase in muscle. Inhibition of insulin-stimulated 2-deoxyglucose uptake again affected the most insulin sensitive muscles. There was a slight but significant change of muscle fiber composition toward less long-chain myosin and more short-chain myosin-containing fibers. Serum cortisol, plasma free fatty acids, and blood glycerol did not change. It is concluded that testosterone administration in moderate doses to oophorectomized female rats is followed by a rapid deterioration of insulin sensitivity in muscle, mediated mainly by perturbations of the insulin receptor glycogen synthesis systems apparently coinciding with changes in muscle morphology. PMID- 1616021 TI - Regulation of glycogen metabolism in canine myocardium: effects of insulin and epinephrine in vivo. AB - Myocardial glycogen synthesis and glucose, lactate, and oxygen extraction were measured in the hearts of anesthetized dogs during infusions of insulin and epinephrine. Glycogen was monitored in vivo using 13C-nuclear magnetic resonance during an infusion of [1-13C]glucose into the left anterior descending artery. Glycogen synthesis was observed during a venous infusion of insulin (1.8 microU.min-1.kg-1), and this newly synthesized glycogen was neither broken down nor was more glycogen synthesized during a subsequent epinephrine infusion (0.5 micrograms.min-1.kg-1). During recovery from epinephrine, glycogen synthesis occurred at 2.1 times the rate seen in the control period. Glycogen synthesis was not stimulated in the absence of epinephrine by control infusions of saline. Glucose uptake was increased by insulin during the control period (from 0.09 to 0.39 mumol.min-1.g-1), so that the combined extraction of glucose and lactate exceeded the requirement for oxidizable substrate calculated from oxygen consumption. The "excess" glucose (0.15 mumol.min-1.g wet wt-1) is presumably available for glycogen synthesis. During recovery from epinephrine, lactate uptake was increased over threefold. Because this additional lactate supplies most of the fuel required for oxidation, the excess glucose available for glycogen synthesis during this period was two times that seen before epinephrine (an average of 0.32 mumol.min-1.g wet wt-1 between 20 and 40 min postepinephrine). These data are consistent with the notion that glycogen synthesis can be activated in the heart without an accompanying increase in glucose uptake by providing an alternative substrate (i.e., lactate) for oxidation. PMID- 1616022 TI - Caffeine ingestion and muscle metabolism during prolonged exercise in humans. AB - We examined the effects of a high-caffeine dose on endurance performance and muscle acetyl group metabolism during prolonged exercise. Eight subjects cycled to exhaustion at approximately 80% maximal oxygen uptake (VO2max) 1 h after ingestion of 9 mg/kg body wt dextrose (Pl) or caffeine (Caf). In the Pl trial, muscle biopsies were taken at rest (1 h postingestion) and at 15 min and exhaustion during exercise. The Caf trial followed the same protocol 1 wk later, with an additional biopsy at the time corresponding to Pl exhaustion. The subjects cycled significantly longer during the Caf trial (96.2 +/- 8.8 min) than in the Pl trial (75.8 +/- 4.8 min). Net glycogenolysis during the initial 15 min of cycling was reduced in the Caf vs. Pl trial (4.7 +/- 1.5 vs. 10.6 +/- 1.3 mmol.kg dry muscle-1.min-1; P less than 0.05). Muscle citrate concentration was increased at rest with Caf (0.59 +/- 0.07 vs. 0.37 +/- 0.05 mmol/kg dry muscle; P less than 0.05) but increased to similar values in both trials during cycling. Caf elevated the acetyl-CoA/CoA-SH ratio at rest (0.316 +/- 0.046 vs. 0.201 +/- 0.023; P less than 0.05) but had no effect on the increases in muscle acetyl-CoA and acetylcarnitine during exercise. The results indicate that Caf before exercise decreased muscle glycogenolysis by approximately 55% over the first 15 min of exercise at approximately 80% VO2max. This "spared glycogen" was available late in exercise and coincided with a prolonged time to exhaustion. Increased utilization of intramuscular triacylglycerol and/or extramuscular free fatty acids after caffeine ingestion may inhibit carbohydrate use at rest and early during exercise via elevations in muscle citrate and the acetyl-CoA/CoA-SH ratio. Muscle acetyl-CoA and acetylcarnitine were maintained above resting contents even at exhaustion when muscle glycogen was depleted. PMID- 1616023 TI - Hepatic metabolism during fasting-refeeding transition in conscious pregnant rabbits. AB - The aim of the present study was to determine changes induced by pregnancy in the hepatic handling of nutrients during the fasting-refeeding transition. Net hepatic and gut substrate fluxes were determined by the Fick principle in conscious pregnant (day 30) and nonpregnant rabbits in the 2 h after consumption of a mixed meal. Hepatic glucose production was suppressed by approximately 50% in both groups from 15 to 90 min. Pregnant rabbits returned to control levels at 120 min. Pregnant females displayed a larger gut glucose output and a greater arterial hyperglycemia. The hepatic and gut balance of lactate as well as the arterial level was almost unchanged. In pregnant females the hepatic uptake and arterial concentration of free fatty acids (FFA) remained almost unchanged, whereas these measures decreased in nonpregnant females by approximately 55 and approximately 80%, respectively, at 120 min. The decline in hepatic output of beta-hydroxybutyrate was similar in both groups. In pregnant rabbits arterial levels of beta-hydroxybutyrate did not parallel changes in the hepatic release as in nonpregnant females. Pregnant females displayed a greater hyperinsulinemia both in the portal vein and the artery over the first hour. It is concluded that, in pregnant rabbits fed a mixed meal, the ability of the liver to handle glucose is impaired because of insulin resistance. The latter brings about a greater and prolonged arterial hyperglycemia, which is reinforced by peripheral insulin resistance. Furthermore, the higher level of FFA may also contribute to the hyperglycemia. As a result, a greater amount of glucose is diverted to other sites, presumably the uterus. PMID- 1616024 TI - Kinetics of 1,25-dihydroxyvitamin D metabolism in the aging rat. AB - To determine whether postmaturational aging influences the kinetics of 1,25 dihydroxyvitamin D [1,25(OH)2D] metabolism in the rat, we measured the metabolic clearance (MCR) and production (PR) rates of 1,25(OH)2D in 6-, 12-, 18-, and 24 mo-old Fischer 344 rats using the constant infusion method. Plasma calcium, phosphorus, and parathyroid hormone (PTH), urinary calcium and phosphorus, and glomerular filtration rate (GFR) were also measured. MCR and PR increased 57 and 91%, respectively (when expressed per rat), and 32 and 39%, respectively (when expressed per kg body wt), between 6 and 24 mo of age, with the greatest increase occurring between 18 and 24 mo. The plasma concentration of 1,25(OH)2D remained unchanged. Plasma PTH, when compared with 6-mo-old animals, was significantly elevated at 18 mo (147%) and even higher at 24 mo (240%). GFR (51Cr-labeled EDTA clearance) remained unchanged through 18 mo but tended to be reduced at 24 mo. Plasma phosphorus tended to decrease with age, whereas plasma calcium, urinary calcium, and urinary phosphorus did not differ among the age groups. These data indicate that both clearance and production of 1,25(OH)2D increase with postmaturational aging in the rat. They also suggest that the early age-related rise in plasma PTH is neither a consequence of low plasma calcium nor of renal insufficiency. PMID- 1616025 TI - Role of leucine and other amino acids in regulating protein metabolism in vivo. AB - The present study examines the independent effects of amino acids and leucine in modulating insulin's effect on leucine kinetics in 24-h fasted conscious dogs during an experimental period where insulin was infused at 600 mU.kg-1.h-1. Group I (n = 7) received saline, group II (n = 10) received sequential infusions of L leucine at 0, 1, 3, and 1 mumol.kg-1.min-1 each lasting for 90 min, and group III (n = 6) received L-amino acids with doses of L-leucine matching those of group II. Plasma leucine (mumol/l) was 120 +/- 5 basally and 135 +/- 23 and 129 +/- 12 during the infusion of 3.0 mumol.kg-1.min-1 in groups II and III compared with 40 +/- 3 in group I. Leucine rate of appearance (mumol.kg-1.min-1) was 3.5 +/- 0.3 during the basal period and was suppressed 80% in both groups II and III as compared with 40% in group I (P less than 0.01). Leucine oxidation (basal = 0.7 +/- 0.15 mumol.kg-1.min-1) dropped 20% in group I but increased to threefold basal in group II and twofold in group III (P less than 0.05). Nonoxidative rate of disposal (basal = 2.6 +/- 0.2 mumol.kg-1.min-1) dropped 25% in group I and 55% in group II but did not change in group III. These data show that, in addition to insulin, amino acids and particularly leucine cause a marked suppression of proteolysis. Availability of all amino acids to prevent hypoaminoacidemia is necessary to sustain basal rates of protein synthesis. The infusion of leucine alone resulted in significant stimulation of leucine oxidation. PMID- 1616026 TI - Linear bone growth of oMT1a-oGH transgenic male mice. AB - Linear bone growth was studied in male mice possessing a controlled ovine metallothionein 1a promoter-ovine growth hormone (oMT1a-oGH) transgene. Transgene expression was activated at weaning by the addition of 25 mM zinc sulfate to drinking water; transgenic and control mice received the zinc supplementation. The ulna, humerus, and tibia were excised at 10-day intervals until 130 days from control and from mice hemizygous for oMT1a-oGH. Bones from mice overexpressing growth hormone (GH) were 11-20% longer than those from controls (P less than 0.01) at 130 days. Transgenic mice exhibited both an enhanced rate of bone growth and a growth period of greater duration, i.e., the ulna, tibia, and humerus from oMT1a-oGH mice grew at an accelerated rate for an additional 20-40 days relative to the same bones from control mice. The bones from both groups were characterized by isometric growth patterns. Genetic size scaling revealed that the observed differences in bone growth were directly related to the mature size of the bone, suggesting that the bones possess an inherent growth pattern that is followed even in the presence of elevated GH. PMID- 1616027 TI - NMR-invisible ATP in heart: fact or fiction? AB - 31P-nuclear magnetic resonance (31P-NMR) spectroscopy is widely used to monitor sequential changes in the nucleoside triphosphate (NTP) pool in intact tissues. Recently, the validity of this technique to quantitate incremental changes in ATP in heart has been challenged. Accordingly, we compared NTP measured by 31P-NMR and by chemical techniques in isolated isovolumic rat hearts at 16 and 56 min of oxygenated perfusion and in hearts subjected to 28 min of hypoxia, with or without 28 min of reoxygenation, and 12 or 28 min of ischemia, with or without 28 min of reperfusion. NTP content was calculated from 31P-NMR spectra using an external standard. At the end of each protocol the heart was freeze-clamped, and NTP and ATP contents were determined by chemical assay. After 16 min of normoxic perfusion the values for NTP and ATP contents measured by both methods in the same hearts were indistinguishable. Results from all seven experimental conditions show no significant difference between methods (P = 0.262). Thus both methods detect the same incremental change in NTP and ATP. PMID- 1616028 TI - Roles of paraventricular catecholamines in feeding-associated corticosterone rhythm in rats. AB - Effects of local destruction of the brain catecholaminergic neurons were examined on the light- and feeding-associated circadian rhythms in plasma corticosterone in rats. 6-Hydroxydopamine (6-OHDA), a selective and long-lasting neurotoxin of the catecholaminergic neurons, was microinjected into the following discrete areas of the brain: the paraventricular nucleus (PVN), median eminence (ME), suprachiasmatic nucleus (SCN), ventromedial hypothalamic nucleus (VMH), lateral hypothalamic nucleus (LH), and the ascending bundle of noradrenergic neurons (NAB). And the feeding-associated as well as the light-associated circadian rhythms in plasma corticosterone were determined. The light-associated circadian rhythm was assayed under a 24-h light-dark cycle with free access to food, whereas the feeding-associated circadian rhythm was measured under restricted daily feeding in which rats had free access to food at a fixed time of day. 6 OHDA reduced the norepinephrine concentrations in respective regions to 10-30% of the control value, except for the LH. The light-associated circadian rhythm was not affected by 6-OHDA into the SCN or PVN. By contrast, 6-OHDA into the PVN or ventral NAB suppressed the feeding-associated circadian peak. 6-OHDA into the VMH and LH showed some effects on plasma corticosterone level but not on the feeding associated circadian rhythm. 6-OHDA had no systematic effect on plasma corticosterone level when injected into the SCN, ME, and dorsal NAB. These findings indicate that the catecholaminergic neurons projecting to the PVN are involved in the feeding-associated but not in the light-associated circadian rhythms. PMID- 1616029 TI - Kidney IGF-I and renal hypertrophy in GH-deficient diabetic dwarf rats. AB - Insulin-like growth factor I (IGF-I) has been proposed as a renotropic factor in initial diabetic kidney growth. To examine the effects of an isolated growth hormone (GH) and IGF-I deficiency on diabetic renal hypertrophy, dwarf rats were made diabetic and studied over a period of 7 days. Diabetic dwarf rats treated with human GH (hGH) or insulin and diabetic rats with intact pituitary were used as controls. In diabetic control animals kidney weight had increased by day 2 (P less than 0.01), and the increase amounted to 27% after 7 days, whereas untreated diabetic dwarf rats had a slower and lesser degree of kidney weight increase, reaching significance on day 7 only, amounting to 8%. hGH administration in diabetic dwarf rats increased the kidney weight on day 7 when compared with untreated diabetic dwarf rats (P less than 0.05) and was 19% over that of insulin treated diabetic dwarf rats. The glomerular volume had increased by 43% in untreated diabetic control rats at day 7, compared with a 29% increase in untreated diabetic dwarf rats (P less than 0.05). hGH administration in diabetic dwarf rats increased the glomerular volume by 46%, comparable to the increase seen in diabetic control animals. Kidney IGF-I was increased on day 2 by 51 and 46% in saline- and hGH-injected diabetic dwarf rats, respectively, but a significantly higher increase in kidney IGF-I amounting to 96% was seen in diabetic control rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616030 TI - Tracer-to-tracee ratio for analysis of stable isotope tracer data: link with radioactive kinetic formalism. AB - A kinetic formalism for the analysis of stable isotope transient tracer data is developed by establishing the link with the formalism available for radioactive tracer data. The crucial variable is the tracer-to-tracee ratio. By expressing the measurements in terms of this ratio, the conventional kinetic formalism used for radioactive data can be applied to estimate noncompartmental parameters using stable isotope tracer data. The tracer-to-tracee ratio also plays an important role in compartmental modeling. By considering the tracer masses in the compartments as state variables the system-experiment model can be written in a format analogous to that usually adopted for the radioactive tracer. Finally, it is shown that the tracer-to-tracee ratio also plays a role in a test of the endogenous steady-state assumption. PMID- 1616031 TI - Increased apolipoprotein A-IV in rat mesenteric lymph after lipid meal acts as a physiological signal for satiation. AB - Chylomicron transport and apolipoprotein A-IV (apo A-IV) output in mesenteric lymph increases significantly after a lipid meal. Mesenteric lymph collected from lymph-fistula rats after lipid infusion exerted an anorectic effect on 24 h fasted rats after administration through chronically indwelling right atrial catheter. Lymph before lipid infusion and lymph collected from a rat fed lipid plus Pluronic L-81 (a potent inhibitor of chylomicron formation) had no anorectic effect. Chylomicron and apo A-IV-rich lymph lost its anorectic effect after specific immunoprecipitation of apo A-IV by a monospecific antibody. Intravenous infusion of the same amount of purified apo A-IV as in chylous lymph 6-8 h after a lipid meal suppressed food intake. This unique physiological function of apo A IV is not shared by apolipoprotein A-I. It is proposed that apo A-IV is a circulating signal released in response to fat feeding and that it is likely to mediate the anorectic effect of a lipid meal. PMID- 1616032 TI - Release of reactive oxygen by hepatocytes on reoxygenation: three phases and role of mitochondria. AB - Reoxygenation of isolated hepatocytes in primary culture resulted in a three phase response in the release of reactive oxygen species (ROS) as determined by peroxidase-dependent luminol chemiluminescence. Release of ROS within the first and second phase correlated well with the extent of reoxygenation injury, both being most significant after approximately 4 h of hypoxic incubation. During the third phase, some of the ROS were released by already nonviable cells. Both antimycin A and rotenone significantly increased release of ROS, indicating severe alterations of the mitochondrial respiratory chain caused by hypoxia and suggesting that the altered mitochondrial respiratory chain represents an important source for the release of ROS on reoxygenation. Generation of ROS rose sharply when the O2 content was increased from 0 to 2%, whereas a further increase in the O2 content, of up to 95%, resulted in only small but steady increases in the formation of ROS. The latter suggests that, in addition to enzymatic sources such as the mitochondrial respiratory chain, nonenzymatic reactions may also contribute to the formation of ROS on reoxygenation. PMID- 1616033 TI - Macromolecular transport by rat gastric mucosa. AB - We previously demonstrated that the stomach is capable of mounting a type I hypersensitivity reaction to luminal antigen challenge. These findings imply that antigenically intact macromolecules cross the gastric mucosa. To test this hypothesis, rat gastric mucosa was mounted in Ussing chambers, and bovine serum albumin (BSA, 0.5 mg/ml) and 125I-labeled BSA (10 microCi) were added to mucosal fluids. After equilibration, serosal fluids were sampled for two 30-min periods, and fluxes of immunologically intact BSA (determined by an enzyme-linked immunosorbent assay) and total BSA (125I-BSA) were calculated under basal conditions and in the presence of NaF and colchicine, and at 4 degrees C. Additional experiments examined macromolecular permeability in sensitized challenged tissues. Immunologically intact BSA (21.3 +/- 4.5 ng.30 min-1.cm-2) crossed the gastric mucosa as approximately one-fourth of the total BSA flux (78.2 +/- 7.5 ng.30 min-1.cm-2). The uptake of immunologically intact BSA was significantly reduced by NaF, an inhibitor of ATP production and endocytosis; colchicine, which inhibits polymerization of cytoskeletal microtubules; and at 4 degrees C, a general metabolic inhibitor. The transmural passage of antigen was not significantly altered by immunoglobulin E-mediated anaphylaxis. These findings indicate that intact protein antigens cross the gastric mucosa by an active, energy-dependent mechanism that uses the microtubular network. PMID- 1616034 TI - Inflammation causes hyperplasia and hypertrophy in smooth muscle of rat small intestine. AB - Inflammation of the rat jejunum with Trichinella spiralis causes altered smooth muscle contractility by day 6 postinfection (PI). We investigated the association of structural change in the smooth muscle layers with inflammation. By day 6 PI, smooth muscle area in cross sections of jejunum increased (P less than 0.05) in longitudinal (LM) and circular (CM) muscle layers. Nuclei counting in cross sections showed that cell number increased two- to threefold in CM and LM, and this increase was not reversed on day 23 PI. Estimation of cell size showed significant hypertrophy by day 6 PI in both muscle layers. [3H]thymidine autoradiography showed that the labeling index (LI) of jejunal LM and CM increased sharply on day 4 PI and peaked on day 6 PI (10- to 15-fold increase). The noninflamed ileum showed a smaller trophic response, with no significant change in area or nuclei number, the LI was increased only on day 6 PI in the ileal CM and was unchanged in LM. Thus extensive hyperplasia and hypertrophy of smooth muscle cells are associated with intestinal inflammation. PMID- 1616035 TI - Effect of diet on glucose transporter site density along the intestinal crypt villus axis. AB - High-carbohydrate diets stimulate intestinal brush-border glucose uptake and increase the number of glucose-protectable phlorizin binding sites, but it has been unknown where along the crypt-villus axis these effects are expressed. We attacked this problem by three methods. First, by measuring phlorizin binding to isolated mouse enterocytes fractionated along the crypt-villus axis by the Weiser method, we identified a high-affinity binding site predominating from villus tip to midvillus and a site of possibly lower affinity predominating in the crypts. A high-carbohydrate diet increased by severalfold the density of the villus sites and probably also of the crypt sites, without changing their binding constants. Second, autoradiography revealed increased glucose-protectable phlorizin binding along the whole crypt-villus axis on a high-carbohydrate diet. Finally, a polyclonal antibody against the Na(+)-glucose cotransporter recognized a protein in the brush-border membrane of villus cells. Hence, substrate-dependent upregulation of intestinal glucose transport involves increased numbers of transporters along the crypt-villus axis. PMID- 1616036 TI - Crypt-villus site of glucose transporter induction by dietary carbohydrate in mouse intestine. AB - Intestinal brush-border glucose uptake rate is regulated by dietary carbohydrate level. However, this uptake response takes a day or more after a change in dietary carbohydrate level. Is this dietary signal perceived in the crypts, and is the glucose transporter activity of enterocytes irreversibly programmed there? If so, this time lag could reflect cell migration times along the crypt-villus axis, since glucose transport is not fully expressed until cells reach the midvillus. Alternatively, however, the time lag could arise from the induction process itself, if glucose transporter activity in mature villus enterocytes can be reversibly reprogrammed by dietary carbohydrate levels. Hence, we measured glucose-protectable phlorizin binding (as a measure of glucose transporter site density) in mouse enterocytes fractionated along the crypt-villus axis by the Weiser method, as a function of time after an abrupt switch in dietary carbohydrate level. For an increase or decrease in dietary carbohydrate, an increase or decrease in phlorizin binding site density first appeared in the crypts and marched over the course of several days to the villus tips. Hence, the signal for glucose transporter regulation is perceived in the crypts, and the observed lag in uptake is due largely to cell migration times. PMID- 1616037 TI - Patch-clamp recording in myenteric neurons of guinea pig small intestine. AB - The results of our research established the feasibility of applying patch-clamp methods in the study of the cellular neurophysiology of myenteric neurons enzymatically dissociated from adult guinea pig small intestine. Recording in current-clamp mode revealed two populations of neurons. One population discharged repetitively during depolarizing current pulses and displayed anodal-break excitation reminiscent of S/type 1 myenteric neurons. In the second population, spike discharge was limited to one or two spikes at the onset of depolarizing pulses and was similar to the behavior of AH/type 2 neurons. Recording in voltage clamp mode revealed a complex of overlapping inward and outward whole cell currents. Fast and slow components of inward current were interpreted as sodium and calcium currents, respectively. Outward currents were blocked by cesium and consisted of components with properties of delayed rectifier current and A-type potassium current. PMID- 1616038 TI - Hormonal regulation of paracellular permeability in isolated rat hepatocyte couplets. AB - Many hormones and drugs exert their effects on cells by increasing cytosolic Ca2+ (Cai2+) and activating protein kinase C (PKC). Each of these actions results in cholestasis in the isolated perfused rat liver, but the responsible mechanisms are unclear. We used isolated rat hepatocyte couplets to observe the direct effects of increased Cai2+ and PKC activation on permeability of the hepatocyte tight junction and canalicular volume, two possible determinants of hepatocyte bile secretion. Couplets were stimulated with the Ca2+ agonist vasopressin (10( 8) M) in the absence and presence of the Ca2+ influx antagonist Ni2+ (5 x 10(-3) M) or with the PKC activator phorbol dibutyrate (10(-6) M). Cai2+ was determined by ratio microspectrofluorometry of indo-1, permeability of the couplet tight junctions was assessed by exclusion of horseradish peroxidase from the canalicular space, and changes in canalicular volume over time were measured directly by optical planimetry. Canalicular volume increased by 1.6 +/- 2.5%/min (mean +/- SD) under basal conditions. In response to vasopressin, there was a rapid 15-fold increase in Cai2+, followed first by an increase in paracellular permeability, then by canalicular collapse (15.9 +/- 5.9%/min). Pretreatment with Ni2+ markedly decreased the vasopressin-induced increase in Cai2+ and abolished both the increase in paracellular permeability and the canalicular collapse. Phorbol dibutyrate also increased paracellular permeability but resulted in neither increased Cai2+ nor canalicular collapse. The PKC inhibitor H-7 reversed the effects of both vasopressin and phorbol dibutyrate on tight junction permeability. Bile secretory pressure, measured in isolated perfused rat liver preparations, was acutely increased by vasopressin, but the increase was augmented rather than inhibited by Ni2+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616039 TI - Vagus-dependent disruption of interdigestive canine motility by gastric distension. AB - The purpose of this study was to determine the effect of proximal gastric distension on interdigestive patterns of canine gastrointestinal motility and to examine the role of extrinsic nerves in regulating such an effect. Serosal electrodes were placed on the antrum, duodenum, and jejunum. Animals were studied before and after transthoracic vagotomy or after neural isolation of the entire jejunoileum (extrinsic denervation). Proximal gastric distension for 5 h was provided by inflating with air a thin complaint bag placed into the proximal stomach after the onset of phase III of the migrating motor complex (MMC). Four volumes (0, 1.5, 12.5, and 25 ml/kg) were each tested four times in each animal. In neurally intact animals, gastric distension with volumes of 12.5 and 25 ml/kg consistently abolished the MMC in the antrum (100%), duodenum (96%), and proximal jejunum (greater than or equal to 62%), but less often in distal jejunum (greater than or equal to 25%). After vagotomy, gastric distension did not inhibit cycling of the MMC in the antrum, duodenum, or proximal or distal jejunum. After extrinsic denervation of the jejunoileum, gastric distension inhibited the MMC in the antrum and the duodenum but had no effect in the proximal or distal jejunum. These findings suggest that nonnutrient proximal gastric distension may contribute to postprandial changes in patterns of myoelectric activity in the upper gastrointestinal tract and that this effect is mediated by the vagus nerves. PMID- 1616040 TI - Hepatic uptake of 3,5,3'-triiodothyronine: electrochemical driving forces. AB - We used the multiple indicator dilution technique to assess the electrochemical forces driving uptake of 3,5,3'-triiodo-L-thyronine (T3) across the basolateral plasma membrane in the single-pass perfused rat liver. With the use of 4 g/dl albumin solutions, the influx and efflux clearances were 0.020 +/- 0.005 and 0.0049 +/- 0.0017 (SE) ml.s-1.g liver-1, respectively, indicating that the total T3 concentration at equilibrium should be about four times greater in cytoplasm than in plasma. However, when the influx and efflux clearances were divided by the unbound (free) T3 concentration in the perfusate and cytosol, they were not different (3.76 +/- 0.26 vs. 4.30 +/- 0.38 ml.s-1.g liver-1), indicating that the uptake process does not generate a gradient of unbound T3 across the plasma membrane. To further test whether T3 uptake is driven by the electrical potential difference across the plasma membrane, liver cells were depolarized by isosmotic replacement of perfusate chloride with gluconate. There was no effect on uptake or efflux. To test whether uptake is coupled to influx of sodium, perfusate sodium was replaced with choline. Although there was a modest decline in both the influx and efflux clearances, there was no change in their ratio, as would be expected for sodium-coupled active transport. These results indicate that uptake of T3 across the basolateral hepatocyte membrane occurs by passive diffusion. We found no evidence to support concentrative, active transport by either electrogenic or sodium-coupled mechanisms. PMID- 1616041 TI - Both CCK-A and CCK-B/gastrin receptors mediate pepsinogen release in guinea pig gastric glands. AB - We evaluated the affinity of cholecystokinin octapeptide (CCK-8), gastrin, and subtype-selective CCK agonists for CCK/gastrin receptors and compared it with the ability of these peptides to stimulate phosphoinositide (PI) hydrolysis and pepsinogen release in guinea pig gastric glands. Competitive binding studies using 125I-labeled Bolton-Hunter-CCK-8 and 125I-gastrin showed the presence of CCK-B/gastrin receptors in gastric glands and dispersed chief cells. In contrast, the potency of peptides in stimulating PI hydrolysis in both gastric glands and dispersed chief cells displayed a profile similar to CCK-A receptors found in pancreatic acini, i.e., CCK-8 = A 71378 greater than A 71623 greater than A 70874 much greater than A 72962 = CCK-8 (desulfated) greater than gastrin II greater than gastrin I. In general, the rank order of potency of peptides for stimulation of PI hydrolysis correlated well with their ability to stimulate pepsinogen release. At concentrations greater than 10 microM, efficacies of gastrin I and II in stimulating pepsinogen release from gastric glands were near 90% of the maximal activity of CCK-8. The inhibitory potency of MK-329, a selective CCK-A receptor antagonist, was similar against either CCK-8 (10 nM) or gastrin I (10 microM), except that a minor portion (approximately 30-40%) of gastrin I-induced pepsinogen release was insensitive to MK-329. The MK-329-insensitive component was inhibited by CI-988, a potent and selective CCK-B/gastrin receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616042 TI - On the design and interpretation of experiments to elucidate albumin-dependent hepatic uptake. AB - The liver's apparently anomalous extraction of organic anions tightly bound to albumin continues to provoke controversy and confusion. Decisive experiments have proved difficult to design, and mathematical models have usually been constructed to defend one or another putative mechanism to the exclusion of others. To stimulate more decisive experiments and as an aid to interpreting those already reported, we discuss a general formulation of the problem that predicts the clearance pattern to be expected when facilitated dissociation and codiffusion are joint determinants of the uptake flux. The results provide an approach to modeling the various mechanisms by which the concentration of bound ligand at the cell surface could be a driving force for uptake. Further we present new calculations to clarify the interpretation of net ligand clearance when the removal of free ligand is the result of bidirectional fluxes into and out of an unstirred sink. Applied to a previously published comparison of the uptake performances of hepatocytes and polyethylene, the new calculations support the inference that facilitated dissociation of albumin-palmitate complexes occurs at or near the hepatocyte surface. PMID- 1616043 TI - Nitric oxide modulates epithelial permeability in the feline small intestine. AB - The objective of this study was to assess whether inhibition of nitric oxide production leads to increased epithelial permeability in feline small intestine. Local intra-arterial infusion of the nitric oxide synthesis inhibitor NG-nitro-L arginine-methyl ester (L-NAME; 0.025 mumol.ml-1.min-1) was performed in autoperfused segments of cat ileum for 90 min. An exogenous source of nitric oxide, sodium nitroprusside (SNP) was infused (0.025 mumol.ml-1.min-1) for the last 30 min of the 90-min L-NAME infusion. Epithelial permeability was quantitated by measuring blood-to-lumen clearance of 51Cr-labeled EDTA throughout the experiment. An increase of approximately sixfold in mucosal permeability was observed within 30 min of L-NAME infusion and this effect was completely reversed by infusion of either SNP or L-arginine (0.125 mumol.ml-1.min-1). NG-nitro-D arginine-methyl ester (D-NAME) had no effect on mucosal permeability. The increase in epithelial permeability was sufficiently large that rhodamine-dextran (mol wt = 17,200) clearance from interstitium to lumen was increased. Pretreatment with IB4, a monoclonal antibody directed against the leukocyte adhesive glycoprotein complex (CD11/CD18) did not prevent the L-NAME-induced increase in epithelial permeability. These data suggest that inhibition of nitric oxide production leads to a reversible circulating leukocyte-independent increase in epithelial permeability. PMID- 1616044 TI - Dietary control of the lactase mRNA distribution along the rat small intestine. AB - At weaning, the lactase-phlorizin hydrolase (LPH) mRNA was shown to disappear specifically from the distal part of ileum while remaining abundant in the more proximal segments of the small intestine. The purpose of this study was to analyze the longitudinal distribution of this transcript in rats whose intestinal lumen content was modified before and after weaning. Preweaned animals force-fed with an artificial diet retained a high amount of LPH mRNA in the jejunum, whereas this transcript precociously decreased in the distal ileum. Conversely, prolonged nursing delayed the specific decay of the LPH mRNA in the latter segment. Food deprivation in preweaned animals did not alter the longitudinal distribution of this transcript in that it remained abundant in the distal ileum. In adult rats, rearranging the order of the small intestinal segments with regard to the intraluminal flow of nutrients did not modify the typical distribution of the LPH mRNA. These results suggest that switching over from milk to the adult type diet at weaning contributes to the modification of the longitudinal distribution of the LPH mRNA that normally occurs at this stage. However, once the adult pattern of expression of this transcript is established, it cannot be significantly altered by changing the position of each intestinal segment as well as its luminal content. PMID- 1616045 TI - Electric and motor patterns associated with canine jejunal transit of liquids and solids. AB - Our hypothesis was that the direction of liquid transit through the canine jejunum is determined by the direction that single jejunal pressure waves spread, while the direction of solid transit depends on the direction of spread of both single waves and clustered waves. In six dogs, 80-cm jejunal Vella loops were made and fitted with manometric catheters and serosal electrodes. After recovery, transit of liquids (Ringer lactate) and solids (2.4-mm nylon spheres) placed into the center of the loop was determined in the conscious animals while pacing the loop in a forward direction or in a backward direction. Under fasting and fed conditions, single pressure waves followed the direction of pacing, while the direction of migration of clustered waves was not determined by the direction of pacing. Liquid transit always followed the direction of single pressure waves. In contrast, solids moved distally regardless of the direction of pacing, except when liquids were also present in the lumen, in which case solids moved in the same direction as the single pressure waves. PMID- 1616046 TI - Relative potency of endothelin analogues on changes in gastric vascular resistance. AB - The purpose of this study was to examine the effects of several endothelin analogues on the gastric microcirculation. We measured changes in vascular resistance of an ex vivo gastric segment of chloralose-anesthetized dogs. Changes in luminal pressure were used to quantitate contractile force. Graded doses of endothelin-2 (ET-2), endothelin-3 (ET-3), [Ala3,11]endothelin (Ala-ET), and the COOH-terminal hexapeptide (ET-C) were infused intra-arterially to the stomach. ET 2 and Ala-ET produced dose-related sustained increases in vascular resistance (10(-10) to 10(-8) M), with Ala-ET less potent than ET-2. In contrast, ET-3 was a weak vasoconstrictor while ET-C had no significant effects. There were no detectable changes in filtration with any of these analogues. However, the force of gastric contractions was significantly attenuated by both ET-2 and Ala-ET in a dose-dependent manner. We found that endothelin analogues produced sustained vasoconstriction of the gastric segment with a potency order of ET-2 greater than Ala-ET-3 much greater than ET-C. Our results suggest that endothelin analogues are potent vasoconstrictors but have little effect on filtration across the gastric vasculature. PMID- 1616047 TI - Altered regulation of regional sucrase-isomaltase expression in diabetic rat intestine. AB - Increased sucrase-isomaltase (SI) expression is a prominent feature of adaptive changes observed in the small intestine of streptozocin-treated chronically diabetic (CD) rats. In this study, we examine the cellular and molecular basis of increased SI expression in CD rats by determining SI specific activities and mRNA abundance in sequentially isolated enterocytes along the villus-to-crypt axis of proximal jejunum and distal ileum. In all regions, two- to fourfold increases in sucrase activity in diabetic rat enterocytes were paralleled by increases in SI mRNA. However, analogous to nondiabetic rat intestine, no differences in SI mRNA abundance were observed between corresponding enterocyte fractions from ileum and jejunum of diabetic rat intestine. By nuclear run-on assays, differences in rates of SI gene transcription were not observed in diabetic and nondiabetic intestinal tissues. We conclude that diabetes induces increased total and specific activities and mRNA abundance of intestinal SI, largely through the stabilization of SI mRNA. Furthermore, analogous to nondiabetic small intestine, differences in proximal-to-distal SI expression appear to be determined at the translational or posttranslational level. PMID- 1616048 TI - Convective movement of Ca2+ across guinea pig gallbladder epithelium. AB - Recently, much interest has developed in biliary calcium because of its importance in the pathogenesis and composition of gallstones. While much progress has been made in understanding the thermodynamic factors that control biliary calcium concentrations, little is known about the kinetic factors that control the movement of calcium across the gallbladder epithelium. These studies measure guinea pig gallbladder epithelial permeability to Ca2+ during in vivo convective water movement across the membrane. Water movement, ranging from -15.2 (absorption) to 6.3 microliters.min-1.cm-2 (water entry), was induced by placing hypotonic, isotonic, and hypertonic solutions into the gallbladder lumen. Calcium movement was found to be directly and linearly related to water flow, indicating that Ca2+ moved with the convective water flow, presumably across paracellular channels. The slope of this relationship (0.602), representing the concentration of calcium in the fluid translocated across the gallbladder epithelium, was only about half that of plasma or luminal contents, indicating that calcium movement across the membrane was restricted. The mean sieving coefficient (1 - r) of guinea pig gallbladder, calculated from this slope, was approximately 0.5, indicating that the epithelium is only moderately permeable to Ca2+. The results suggest that intraluminal chelation of Ca2+ for the possible prevention and/or treatment of calcium-containing gallstones is a potentially feasible therapeutic modality. PMID- 1616049 TI - In vitro hyporeactivity to methoxamine in portal hypertensive rats: reversal by nitric oxide blockade. AB - The endothelial cell plays an important role in the local control of vascular smooth muscle tone. Portal hypertension is accompanied by systemic vasodilatation and a decreased response to vasoconstrictors, changes especially evident in the superior mesenteric arterial bed. To evaluate a possible effect of the locally released endothelium-derived relaxing factor nitric oxide (NO), we tested the effect of NO blockade in in vitro perfused superior mesenteric arterial beds of normal (sham) and portal hypertensive (PVL) rats, induced by partial portal vein ligation. A significant (n = 7/group; P = 0.02) hyporeactivity to the vasoconstrictive properties of the alpha-adrenoceptor agonist methoxamine (3 x 10(-6) to 3 x 10(-4) M) was prevented by blocking NO formation in PVL compared with sham rats, using the stereospecific biosynthesis antagonist N omega-nitro-L arginine (10(-4) M, n = 7/group; NS for all methoxamine concentrations tested). This effect was reversed by the NO precursor L-arginine (10(-3) M, n = 5/group). In conclusion, these in vitro results in mesenteric vessels demonstrate that 1) portal hypertension is accompanied by a hyporeactivity to the vasopressor methoxamine and 2) locally released NO in this preparation is responsible for the decreased vasoconstrictive response. PMID- 1616050 TI - Structure, function, and regulation of cellular tight junctions. AB - The tight junction (TJ) is a dynamic structure that is controlled, in part, by the activity of the cytoskeleton. It has become abundantly clear that, in the presence of Ca2+, assembly of the TJ is the result of cellular interactions that trigger a complex cascade of biochemical events that ultimately lead to the formation of an organized network of TJ elements, the composition of which remains unknown. The TJ functions both as a barrier between two fluid compartments and, to a lesser extent, as a fence between apical and basolateral membrane domains. To meet the many physiological and pathological challenges to which epithelia and endothelia are subjected, the TJ must be capable of a rapid and coordinated response, which depends on complex regulatory mechanisms. The precise characterization of the mechanisms involved in the assembly and regulation of the TJ is an area of current active investigation. However, until the biochemical composition of this structure has been defined and its gene identified, the TJ will continue to be an elusive yet tantalizing challenge to the cell biologist. PMID- 1616051 TI - Rabbit lung surfactant protein A gene: identification of a lung-specific DNase I hypersensitive site. AB - Expression of the gene encoding pulmonary surfactant protein A, SP-A, is lung specific and developmentally and hormonally regulated. Previously, we observed that SP-A gene transcription is initiated in fetal rabbit lung after day 21 of gestation and reaches maximal levels by day 28. In the present study, a cDNA specific for rabbit SP-A was used to isolate the SP-A gene from a rabbit genomic library. A 7.6-kb fragment containing the entire structural gene and approximately 380 bp of 5'-flanking DNA was isolated and characterized. The transcription initiation site, mapped by primer extension analysis, was localized 23 bp downstream of a putative TATA element. The structural gene is composed of five exons and four introns. The first exon encodes the 5'-untranslated region of the mRNA; the translation initiation site is in exon II, and exon V contains the two polyadenylation sites that give rise to the 2.0- and 3.0-kb species of SP-A mRNA. A potential adenosine 3',5'-cyclic monophosphate (cAMP)-regulatory element (CRE) was identified at -261 bp, and sequences with homology to glucocorticoid regulatory element (GRE) half-sites were found at -150 and -190 bp upstream of the transcription initiation site and within the first intron. A DNase I hypersensitive site was identified in genomic DNA isolated from 21- and 28-day fetal and adult rabbit lung tissues. This site was mapped within the 5'-flanking region of the SP-A gene, at approximately -80 to -180 bp upstream of the transcription initiation site. The absence of this hypersensitive site in genomic DNA of liver, kidney, and heart tissues suggests that altered chromatin structure may serve a role in lung-specific SP-A gene expression. The presence of this tissue-specific DNase I hypersensitive site in lung nuclei from 21-day gestational age fetal rabbits suggests that the SP-A gene may exist in an accessible conformation prior to the time of transcription initiation. PMID- 1616052 TI - Effects of TNF-alpha and phorbol ester on human surfactant protein and MnSOD gene transcription in vitro. AB - Tumor necrosis factor-alpha (TNF-alpha) and the phorbol ester, 12-O-tetradecanoyl phorbol-13-acetate (TPA) decrease the synthesis of surfactant proteins association with decreased SP-A and SP-B mRNA. Nuclear run-on assays were utilized to test whether the inhibitory effects of TNF-alpha and TPA were associated with changes in surfactant protein gene transcription. SP-A gene transcription was inhibited by both TNF-alpha and TPA as assessed by nuclear run on assays. Inhibitory effects of both agents on SP-A gene transcription were readily detected within 6 h after exposure and persisted for 24 h. While TNF alpha and TPA decreased cellular SP-B mRNA content, transcription of the SP-B gene was not influenced by these agents. In contrast to the inhibitory effects of TPA and TNF-alpha on SP-A and SP-B mRNAs, steady-state mRNA and rate of transcription of human manganese superoxide dismutase (MnSOD) were increased by both agents. The time course and extent of increased MnSOD gene transcription by TNF-alpha and TPA were distinct. Transcription of the human beta-actin gene was not altered by either agent. The inhibitory effects of TPA and TNF-alpha on SP-A expression in pulmonary adenocarcinoma cells are associated with the inhibition of SP-A gene transcription. Loss of SP-B mRNA was not accompanied by decreased SP B gene transcription. Actinomycin D blocked the inhibitory effects of TNF-alpha and TPA on SP-A and SP-B mRNA, supporting a role for posttranscriptional events in the modulation of the expression of the surfactant proteins SP-A and SP-B. PMID- 1616053 TI - Arachidonic acid increases cholinergic secretory responsiveness of ferret tracheal glands. AB - The purpose of this study was to determine if arachidonic acid could alter ferret tracheal gland secretory responsiveness to a cholinergic agonist. We prepared glandular explants and incubated the explants in medium containing [3H]glucosamine. Secretory responsiveness was expressed as the percent change in basal secretion of acid-precipitable [3H]glucosamine-labeled glycoconjugates induced by the addition of agonist with and without arachidonic acid [mean +/- SE (n)]. Addition of 10(-3) M arachidonic acid caused a significant increase in secretion [28 +/- 6% (n = 6)] compared with untreated control tissues [-10 +/- 4% (n = 7), P less than or equal to 0.05]. Carbachol (10(-7) M) increased secretion 39 +/- 9% (n = 7). The combination of 10(-3) M arachidonic acid and 10(-7) M carbachol elicited a significantly greater change in secretion compared with either agent alone [173 +/- 50% (n = 5)]. The addition of nordihydroguaiaretic acid (10(-6) M) or indomethacin (10(-6) M) partially attenuated the arachidonic acid-enhanced secretory responsiveness to carbachol. Treatment with both blockers completely inhibited the arachidonic acid-enhanced secretory responsiveness to carbachol. The effect of arachidonic acid on cholinergic stimulation was also abolished by treating the explant cultures with tetrodotoxin (10(-7) M). This hypersecretory state is most likely mediated by eicosanoid-induced release of neurotransmitters from nerve terminals. PMID- 1616054 TI - Binding, uptake, and localization of surfactant protein B in isolated rat alveolar type II cells. AB - This study reports the ability of rat alveolar type II cells to internalize mature bovine surfactant protein B (SP-B) in vitro. Isolated type II cells were incubated with labeled SP-B, and binding and internalization were studied biochemically and morphologically. Biochemical analyses demonstrated a time dependent association of 125I-labeled SP-B with type II cells; binding steadily increased through 4 h and then remained constant through 20 h of incubation. The association of [3H]SP-B with type II cells was characterized via light and electron microscopic autoradiography. Significant quantities of [3H]SP-B were found at the plasma membrane, in the endocytic pathway, and in lamellar bodies. The pathway of SP-B internalization was not altered by the presence of whole rat surfactant; however, the quantity of SP-B internalized into lamellar bodies was increased. 3[H]SP-B was not associated with coated pits and colocalized with horseradish peroxidase (HRP), consistent with receptor-independent internalization. Cell-associated SP-B was not degraded and was detected in lamellar bodies undergoing exocytosis. These results suggest that SP-B may follow a recycling pathway similar to that previously reported for surfactant phospholipids. PMID- 1616055 TI - Release of reactive oxygen species by guinea pig tracheal epithelial cells in vitro. AB - Regulatory and stimulatory mechanisms of H2O2 release from guinea pig tracheal epithelial cells were investigated. Cells in primary culture maintained in a previously described air-liquid interface system released H2O2 to the extracellular space only from the apical side of the cells. The rate of release was 0.044 +/- 0.003 nmol.min-1.mg protein-1. H2O2 release could be stimulated significantly during a 30-min incubation period with phorbol myristate acetate (PMA) and platelet-activating factor (PAF). A stimulatory effect of PAF was achieved at concentrations greater than 100 nM and with PMA at concentrations greater than 10 ng (16 nM). When protein kinase C was inactivated with staurosporine, the responses to both PAF and PMA were abolished, whereas the cyclooxygenase inhibitor, indomethacin, did not affect H2O2 generation. When guinea pig tracheal epithelial cells were exposed to sublethal concentrations of extracellular H2O2 (30 microM), H2O2 was detoxified from both apical and basal sides, H2O2 removal being significantly more rapid from the apical side of the cells. These results suggest that tracheal epithelial cells can be stimulated to generate reactive oxygen species into the airway lumen and that this occurs in response to inflammatory mediators that act through protein kinase C. Luminal H2O2 release may have developed as a defense mechanism against microbes, and, similarly, luminal detoxification of H2O2 could represent an important mechanism of modulation of airway inflammation in response to oxidant stress. PMID- 1616056 TI - Differentiated structure and function of cultures from human tracheal epithelium. AB - Here we describe the conditions which allow cultured human tracheal epithelial cells to retain the ion transport properties and ultrastructure of the original tissue. The order of potency of growth supports and media additives in elevating baseline short-circuit current (Isc) and responses to mediators were vitrogen gel (VIT) greater than extracellular matrix from bovine corneal endothelial cells (ECM) greater than human placental collagen (HPC), and 2% Ultroser G serum substitute (USG) greater than 5% fetal calf serum (FCS) greater than defined growth factors (GF). For all combinations of medium and growth supports, an air interface (AIR) gave better electrical properties than immersion feeding (IMM). As opposed to our earlier conditions (HPC/FCS/IMM), the best new combination (VIT/USG/AIR) produced higher baseline Isc (58.0 +/- 10.6 vs. 5.1 +/- 1.0 microA/cm2) and increased Isc responses to isoproterenol (6.1 +/- 1.5 vs. 0.8 +/- 0.3 microA/cm2) and bradykinin (9.6 +/- 2.0 vs. 1.0 +/- 0.2 microA/cm2), while retaining high transepithelial resistance (227 +/- 5 omega.cm2). VIT/USG/AIR led to the appearance of cilia, an increase in the depth of the cell sheets (50 vs. 10 microns), longer and more frequent apical microvilli, and increased interdigitations of the basolateral membrane. Protein and DNA content were also significantly increased. Secretory granules were present which stained with antibody to goblet cells, but not to serous or mucous gland cells. CF cells grown in VIT/USG/AIR showed high baseline Isc (69 +/- 18 microA/cm2) and a proportionately larger inhibition of Isc by amiloride (70 +/- 10 vs. 34 +/- 3%). Isc did not respond to isoproterenol, and the response to bradykinin was 22% normal. PMID- 1616058 TI - A stable O2-resistant cell line: role of lipid peroxidation byproducts in O2 mediated injury. AB - HA-1 hamster fibroblasts receiving fresh media every 24 h were continuously passaged in progressively increasing O2 concentrations for 18 mo (designated O2R95). These cells were significantly more resistant than parental HA-1 to clonogenic inactivation mediated by 95% O2 without media replacement. The O2R95 cell line exhibited increases in the activities of catalase (CAT), Mn superoxide dismutase (MnSOD), Cu,Zn superoxide dismutase (Cu,Zn SOD), and glutathione peroxidase (GPx). O2R95 cells demonstrated uniformly distributed increased staining for CAT, MnSOD, Cu,Zn SOD, and GPx proteins, as determined by immunohistochemistry. Cellular resistance to and metabolism of 4-hydroxy-2 nonenal (4HNE), a toxic byproduct of lipid peroxidation implicated in mechanisms of O2 toxicity, was examined in HA-1 and O2R95 cell lines. O2R95 cells were significantly more resistant to 4HNE cytotoxicity, which was accompanied by a significant increase in 4HNE metabolism. O2R95 cells also demonstrated an increase in total glutathione (GSH) and glutathione S-transferase (GST) activity, an enzymatic system believed to be involved with 4HNE metabolism. Furthermore, homogenates from O2R95 cells consumed greater quantities of 4HNE in the presence of NADPH (but not NADH, NAD+, or NADP+), suggesting that an enzyme(s) utilizing NADPH contributes to 4HNE metabolism, resistance to 95% O2 and 4HNE as well as increased total GSH, antioxidant enzyme activities, and NADPH-dependent metabolism of 4HNE, persisted in O2R95 cells for 75 days of growth in 21% O2. These findings are compatible with the hypothesis that aldehydic byproducts of lipid peroxidation contribute to mechanisms of O2 toxicity and the selective pressure exerted by exposure of cells to hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616057 TI - Effects of surfactant apolipoproteins on liposome structure: implications for tubular myelin formation. AB - Tubular myelin is one of several forms of lung surfactant and may play an important role in its surface activity. To determine possible mechanisms of tubular myelin formation, we studied the effects of purified surfactant proteins (SP-A, SP-B, and SP-C) on large unilamellar dipalmitoylphosphatidylcholine-egg phosphatidylglycerol (7/3; wt/wt) liposomes. We studied different types of membrane interaction induced by the apolipoproteins and correlated these with the observed changes in ultrastructure. Aggregation was assessed by measurement of light absorbance, lysis, and fusion by measurement of the fluorescence emitted by water-soluble and lipid-soluble probes, respectively. Mixtures of the apolipoproteins and liposomes were examined in ultrastructural studies by negative staining and by thin sectioning. We found that each protein had a pronounced and distinct effect on liposome structure. SP-A caused aggregation, whereas SP-B and SP-C also caused extensive leakage of liposome contents (lysis) and some degree of lipid mixing (fusion). The disruptive effects of SP-B and to a lesser extent those of SP-C were correlated by negative staining with the appearance of bilayer disks, which tended to aggregate into large sheets. There was a marked synergy between SP-A and SP-B in the process of membrane fusion in the presence of calcium, which correlated with an early (10 min) and extensive rearrangement of the structures seen by electron microscopy followed by a delayed (24 h) appearance of small amounts of tubular myelin. PMID- 1616059 TI - Surfactant protein A metabolism in preterm ventilated lambs. AB - Surfactant protein A (SP-A) metabolism was studied in vivo in 33 preterm ventilated lambs at 138 +/- 1 days gestational age by measuring recoveries of exogenously administered surfactant containing both radiolabeled SP-A and labeled saturated phosphatidylcholine (Sat PC) given via the trachea at birth. Endogenously secreted SP-A was also labeled with [35S]methionine and followed over 24 h. The exogenously labeled SP-A left the alveolar pool more rapidly than did Sat PC over the first 5 h of life (P less than 0.05), and both exogenously labeled SP-A and Sat PC were detected within lamellar bodies by 2 h, indicating uptake from the airspaces. The quantity of SP-A in alveolar washes increased about twofold from birth to 5 h of age, whereas alveolar Sat PC pools were constant over 24 h. The SP-A endogenously labeled with [35S]methionine was recovered at highest specific activities in the alveolar washes at 10 and 45 min after birth with no labeled SP-A detectable in lamellar body fractions until 2 h. The curve for endogenous SP-A labeling of lamellar bodies was similar to that for exogenous labeling, indicating that SP-A was initially secreted by a pathway independent of lamellar bodies with subsequent SP-A labeling of lamellar bodies. The kinetics of SP-A metabolism were very different than for Sat PC in preterm lambs. PMID- 1616060 TI - Differential extraction for the rapid purification of bovine surfactant protein B. AB - Surfactant protein B (SP-B), a peptide found in organic solvent extracts of mammalian surfactant, has been isolated from surfactant previously by column chromatography and/or preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS/PAGE). We have developed a method for isolation of SP-B from bovine surfactant utilizing differential organic extraction. Dried surfactant, isolated from lavage of excised cow lungs, was delipidated by extraction with diisopropyl ether-butanol (3:2). The aqueous layer, containing surfactant proteins, was dried and then was sequentially extracted with diethyl ether ethanol (3:1) and CHCl3:MeOH:HCl (3:2:0.005 N). SP-B partitioned into chloroform methanol, which was evaporated under N2. Purified SP-B, quantitated by Coomassie dye binding, represented 1% (wt/wt) of the original surfactant with a final phospholipid-to-protein ratio less than 1. Silver-stained SDS/PAGE of the SP-B extract revealed a single band at 9 kDa (reduced) and 18 kDa (nonreduced), which by immunoblotting reacted strongly with monospecific anti-SP-B antibody. Amino acid sequence analysis confirmed the presence of NH2 and N-1 terminal sequences of bovine SP-B. This procedure offers a rapid, reliable method for isolation of purified SP-B from whole surfactant. PMID- 1616061 TI - Relationship between personality type and achievement in an undergraduate physiology course. AB - The Myers-Briggs type indicator (MBTI) was given to 163 students in an undergraduate Human Physiology course at a large state university. Selected MBTI personality types were compared for achievement in the course using a t test to compare total points earned. High grades were earned by students stronger in the traits of introversion (I) and judgment (J), whereas the extraverted (E) and perceptive (P) types had the lowest grades and dropped out of the course in the largest numbers. When combinations of MBTI types were compared, the highest grades were earned as follows: SJ greater than ST greater than IN greater than IJ greater than IS (S, sensing; T, thinking; N, intuitive). This ranking indicates that a sensing personality also has a strong relationship to achievement in this Human Physiology course when it is combined with judgment, thinking, or introversion. Instructors and students need to be aware of the relationship between personality and learning so they can modify their teaching style and learning behavior to enhance academic achievement. PMID- 1616062 TI - Physiology course for secondary school biology teachers. AB - The Department of Physiology at the Medical College of Virginia/Virginia Commonwealth University offered a human physiology course to middle school and high school science teachers in the Richmond, VA, area. It was a three-credit course, team taught, and given at a location convenient to many area teachers. This course served the community by contributing to the continuing education efforts of teachers and concurrently enhanced our recruitment program by advertising "physiology" to teachers who will influence college-bound students for years to come. In addition, we established ties between teachers and physiology faculty such that continuing interactions (e.g., collaborative research during the summer) should be facilitated. The success of the course suggests that this is an effective way to serve local communities, enhance efforts to recruit graduate students into the basic sciences, and at the same time help reverse the educational crisis in the US by bolstering the backgrounds of secondary school teachers. PMID- 1616063 TI - A student apparatus for recording action potentials in cockroach legs. AB - A comparatively simple apparatus allows even beginning students to observe action potentials in the cockroach leg. The recordings are made extracellularly by impaling the leg on two insect pins. Deflection of large spines on the leg, which are each innervated by one sensory neuron, initiates the action potentials. Using this technique, students observe the all-or-nothing nature of action potentials, their coding of information by frequency, and sensory adaptation. PMID- 1616064 TI - Keeping community college faculty current in physiology through utilization of health science center expertise. AB - The maintenance of current knowledge in physiology in community colleges is very difficult to accomplish. The absence of a research environment, limited library facilities, and heavy teaching loads often result in the instructor utilizing the teaching textbook as the primary source of information. A cooperative program between The University of Texas Health Science Center at San Antonio and San Antonio Community College has been developed in which the Health Science Center faculty present updated seminars in physiology topics for the community college faculty. This program has been in existence for three years and has proved to be very effective in improving the quality of the physiology curriculum at the community college. PMID- 1616066 TI - Computer software for physiology education. PMID- 1616065 TI - Breath hydrogen testing as a physiology laboratory exercise for medical students. AB - Breath hydrogen testing (BHT) is a simple and reliable method for identifying impaired carbohydrate absorption. We describe a laboratory exercise in physiology for medical students using BHT as the teaching tool. The students collect fasting samples of expired air from each other using a simple nasal prong technique. They then drink one of several different aqueous carbohydrate solutions. Additional samples of expired air are collected by the students at 90 and 120 min after substrate ingestion and are analyzed by gas chromatography. Between sampling periods, discussions of digestive physiology are provided by the faculty. Students tabulate their BHT results as well as recording any symptoms using a standard scoring system. A total of 460 students have participated. We found that the percentage of students who malabsorbed a given substrate was similar each year. The results obtained in these student exercises closely parallel those reported in the literature. We conclude that BHT is an excellent teaching tool for illustrating carbohydrate digestion and absorption, even when performed by minimally trained subjects. PMID- 1616067 TI - Interactive videodisc calorimetry simulations for exercise physiology laboratories. AB - Six interactive videodisc lessons for college-level exercise physiology classes were developed. The six lessons were written using TenCore for the IBM M-Motion technology. The focus of the laboratories is on exercise metabolism measured by indirect calorimetry. The six lessons are as follows. 1) Environmental measures: determines whether conditions are favorable for exercise. Dry bulb, wet bulb, and black globe temperatures are obtained to calculate relative humidity, STPD gas volumes, and the wet bulb-globe temperature index. 2) Basal metabolism: emphasizes the mechanics of calculating energy expenditure through indirect calorimetry. Lying, sitting, and exercise metabolism are compared. 3) Submaximal metabolism: compares the energy cost of walking a mile and running a mile. Steady state exercise, oxygen debt, and oxygen deficit are explored. 4) Maximal metabolism: assesses maximal oxygen consumption using the Bruce protocol. 5) Hormonal responses to prolonged exercise: demonstrates the effect of hormonal levels on %fat and %carbohydrate utilization during 1 h of exercise. 6) Metabolic responses to supramaximal exercise: estimates anaerobic power using the Wingate test. PMID- 1616068 TI - Behavior as a window on physiology: a simple apparatus for recording caterpillar feeding. AB - Regulation of feeding is a fundamental element of homeostasis. This is reflected in the similarity of control mechanisms in a wide range of animals, including insects and humans. A close examination of feeding behavior can illuminate the physiological processes driving regulation. A simple, inexpensive method for recording fine details of feeding by caterpillars is described. Possible experiments, interpretation of the data, and the relationship of observations to the underlying physiology, are outlined. PMID- 1616069 TI - [Incidence of Borrelia burgdorferi infection in isolated facial paralysis. A prospective study]. AB - Between the causes of facial paralysis, similar to Bell's palsy, recently are included those due to some families of spirochaeta (Borrelia burgdorferi) transmitted through tick-bite. These bacteria, besides de facial palsy, may produce several degrees of lymphocytic meningitis and subsequently the paralysis of the face, sometimes clumsy or recurrent. The treatment being the antibiotic drugs, never the corticoids. In the paper are explained prospectively the incidence of this disease in the AA's environment. PMID- 1616070 TI - [Idiopathic cerebral hernia in the middle ear]. AB - Idiopathic brain herniation into the middle ear and the mastoid process is an infrequent condition. There are only 29 cases reported in the world literature covering the last 40 years. The paper inform on one of those cases, a man, of spontaneous encephalocele and deals with the pathogenesis, the clinical features and the suitable surgical approach. PMID- 1616071 TI - [Alloplastic materials in otological surgery. An update]. AB - Alloplastic materials have been employer as replacement of the ossicular chain, in the reconstruction of the posterior wall of the outer ear and even in filling up the mastoid process. But owing to the restrictive laws in some countries relative to the transplantations of homologous ossicles and first of all for fear of viral transmissions through the procedures a new light is shed in this field of the ear surgery. In the paper the AA, make a critical revision of replacement alloplastic prosthesis considering the lately introduced materials. The majority of the prosthesis, specially those in plastic, give not, either in short or long term, worthy results. Autologous tissues are, as always have been, the first choice in the reconstructive management of the anatomy of the middle ear. Alloplastic materials being the second chance, by virtue of its recognized intolerance at long terms. PMID- 1616072 TI - [2 cases of esophageal perforation by foreign bodies]. AB - The AA. present 2 cases of esophageal perforation due to foreign bodies among 179 esophagoscopies done for removal of other intruders, which required the endoscopic procedure, during a lapse of 4 years. Considerations regarding the treatment and the evolutive course. PMID- 1616073 TI - [Informatics program in the study of patients with Meniere's vertigo]. AB - Meniere's Vertigo is a process of long evolution applying for several clinical variables during many periodical controls. The A. of the paper present an informatics program aiming to compile each patient data regarding these items: 1. a quick knowledge of the evolutive course both clinic and therapeutical experienced by the patient during years; 2. control of the efficacy of the treatments done; and 3. the comparison of own results with those of other authors. In the article are expose the practical development of the program and the data gained with. PMID- 1616074 TI - [Choristoma of the salivary gland and dermoid cyst of the middle ear in a 3-year old girl. Apropos of a case]. AB - We studied a rare instance of salivary gland choristoma and dermoid cyst of middle ear in a 3 years old girl. There are only thirteen cases of salivary choristoma reported and ours is the only one combining choristoma and dermoid cyst of the middle ear published, as far as we know. PMID- 1616075 TI - [Mandibular osteoradionecrosis caused by radiotherapy of lip cancer. Differential diagnosis with tumor recurrence]. AB - The onset of the bone radionecrosis is a relatively unusual problem which should be considered in the differential diagnosis of recurrences of irradiated tumors showing a high degree of aggressiveness. The AA. present a case report of a re operated lower lip carcinoma which underwent further radiation therapy. A bony mandibular lesion was then observed, which led to the diagnosis of tumoral invasion at the mandible, and a partial mandibulectomy was then performed. The histopathological examination revealed a bone necrosis, probably due to radiotherapy. The clinical features and therapeutic management of mandibular osteoradionecrosis are commented. PMID- 1616076 TI - Expanding school health services to serve families in the 21st century. PMID- 1616077 TI - Roles and responsibilities for nursing continuing education and staff development across all settings. American Nurses Association. Council on Continuing Education and Staff Development. PMID- 1616078 TI - Compendium of HIV/AIDS positions, policies and documents. April 1992. PMID- 1616079 TI - Persuasion in clinical practice: rational decision or intuitive belief? PMID- 1616080 TI - Patient-controlled analgesia: a double-blind study in burn patients. AB - A double-blind controlled study was performed to assess the efficacy and safety of patient-controlled analgesia in burn patients. This method was compared with conventional analgesic therapy consisting of intermittent intravenous morphine injections. Twenty-four adult patients hospitalised for burn injuries participated in the study. The McGill Pain Questionnaire, visual analogue scales and verbal-numeric scales were administered at regular intervals to measure various components of the patients' pain experience, degree of pain relief, anxiety levels, adverse side effects and overall treatment efficacy. Although statistical significance was found in only one measure, the results suggested better pain control in patients who were administered morphine by patient controlled analgesia as compared with intermittent injections. Analysis of the side effects showed no difference between the groups. The amount of morphine administered over the trial period was also similar for the two groups but considerable interpatient variability was seen. Although further research is needed to determine the conditions for optimal use of patient-controlled analgesia, it is concluded that it is a safe, effective and improved method for controlling pain in selected burn patients. PMID- 1616081 TI - Admixture of propofol and alfentanil. Use for intravenous sedation and analgesia during transvaginal oocyte retrieval. AB - An admixture of propofol and alfentanil provides adequate sedation and analgesia during transvaginal oocyte retrieval in the absence of a paracervical block. In 100 patients the technique provided haemodynamic stability, sedation which was easily controlled, rapid recovery and universal patient acceptance. PMID- 1616082 TI - Anaesthesia for bullectomy. Use of propofol, high frequency jet ventilation and extradural blockade. AB - A patient with a single large bulla occupying 50% of the right hemithorax was anaesthetised successfully with a combination of techniques not previously described. The technique consisted of extradural analgesia and intravenous infusion of propofol, while ventilation was maintained with high frequency jet ventilation through a single lumen tracheal tube. The advantages of this technique are a reduced risk of barotrauma, good operating conditions and good analgesia. PMID- 1616083 TI - Anaesthesia for intraperitoneal hyperthermic perfusion. AB - Intraperitoneal hyperthermic perfusion is a method of regional chemotherapy shown to be effective in the prevention and treatment of peritoneal metastases. General anaesthesia for a patient who required this procedure is described. Guidelines for management are suggested, with particular emphasis on temperature control, fluid and electrolyte balance and postoperative care. PMID- 1616084 TI - Fibreoptic intubation in cicatricial membranes of the pharynx. AB - Two patients presented with almost total obliteration of the pharynx. In one, a membrane developed after corrosive poisoning; in the other, the oropharynx was filled with a dense cicatrix in the sclerosing phase of rhinoscleroma. In both patients, a single opening in the membrane provided access to both the larynx and oesophagus. Fibreoptic intubation allowed both a thorough assessment of the pathology and subsequently the passage of a cuffed tracheal tube to secure the airway. To overcome the problem of respiratory obstruction while the fibrescope passed through the opening in the membrane, either rapid intubation, or a technique using pre-oxygenation and voluntary hyperventilation followed by breath holding during bronchoscopy, was used. The thin calibre and manoeuvrability of the flexible fibreoptic bronchoscope makes fibreoptic intubation an excellent technique of airway management in cicatricial membranes of the pharynx. PMID- 1616085 TI - Hypotension following valve replacement surgery in carcinoid heart disease. AB - We report the use of adrenaline in a 62-year-old woman with carcinoid heart disease who underwent double valve replacement. She was given an intravenous infusion of octreotide throughout the peri-operative period. Following the termination of cardiopulmonary bypass she developed profound hypotension which proved to be refractory to various therapies but responded to adrenaline. Adrenaline is said to be contraindicated in carcinoid syndrome, but we would suggest the consideration of its use in such cases where the hypotension may result from myocardial depression rather than from a carcinoid crisis. PMID- 1616086 TI - Caudal blockade in the management of aortic thrombosis following umbilical artery catheterisation. AB - A neonate, with a postconceptual age of 29 weeks, suffered thrombosis of the aorta as a consequence of umbilical artery catheterisation. This resulted in ischaemic lesions of the lower limbs and buttocks. Part of the management consisted of the insertion of an extradural catheter, via the caudal route, which provided good pain relief and may have improved lower limb blood flow. PMID- 1616087 TI - Thoracic epidural anaesthesia and primary pulmonary hypertension. AB - Patients with primary pulmonary hypertension occasionally present for surgery. Anaesthesia requires continuous cardiovascular monitoring and maintenance of stable pulmonary and systemic haemodynamics. The management of a patient with severe pulmonary hypertension, undergoing open lung biopsy under a combination of general anaesthesia and thoracic epidural analgesia is reported and the problems of primary pulmonary hypertension are discussed. PMID- 1616088 TI - Functionally crossed pipelines. An intermittent condition by a faulty ventilator. AB - Unexpectedly high blood oxygen tension in intensive care patients occurring over a 5-year period were found to have been caused by an apparently normally functioning ventilator which was intermittently acting as a conduit between the oxygen and air pipelines. Responses to a circular letter sent to Quality Control Pharmacists in England and Wales suggest that similar faults may have occurred at least five times in the past 10 years. Recommendations are given for the prevention of this problem, including monitoring of gas pipeline composition. PMID- 1616089 TI - Spinal epidural anaesthesia. A new combination system. AB - We present our experience with a new combined spinal epidural system through which regional anaesthesia was performed in 30 male patients undergoing suprapubic prostatectomy. The technique consists of two needles, a 17 G Tuohy needle with a hole in its distal curve (back eye) and a 29 G spinal needle which is passed through the back eye before being introduced into the subarachnoid space. We found the back eye combined spinal-epidural system effective and simple to use. The Tuohy needle with its back eye did not impede insertion of the epidural catheter and was a suitable introducer for the thin 29 G spinal needle. PMID- 1616090 TI - Modification to the Sprotte spinal needle. AB - The large lateral hole of the Sprotte needle is claimed to aid cerebrospinal fluid efflux during the performance of spinal anaesthesia. Using theoretical calculations and practical measurement we have shown that reducing the area of the lateral hole to that of the cross sectional area of the needle does not affect the flow rate. We suggest this modified Sprotte needle is an improved design which has the potential advantages of reducing the incidence of inadequate spinal anaesthesia and strengthening the needle tip. PMID- 1616091 TI - Magnetic resonance for the anaesthetist. Part II: Anaesthesia and monitoring in MR units. AB - Anaesthetists are increasingly involved in patient care during magnetic resonance imaging and spectroscopy. This paper describes a system which has been developed for the management of critically ill patients and the conduct of anaesthesia in a magnetic resonance unit with a 1.6 tesla whole body magnet. Difficulties which arise from working in a confined space in a high magnetic field are highlighted. Different approaches to anaesthesia, sedation and the modification of equipment for use in this environment are reviewed. The problems associated with patient monitoring within a magnetic field are discussed and some solutions are suggested. A transport system for critically ill patients is described and a protocol for management is outlined. PMID- 1616092 TI - Pre-registration house surgeons. A questionnaire study of anaesthesia-related knowledge and approach to pre-operative investigations. AB - A group of newly qualified pre-registration House Officers completed a questionnaire relating to their knowledge of anaesthetic drugs and to their appreciation of complications which may, in whole or in part, have required some knowledge of anaesthesia. Considerable gaps in knowledge were demonstrable, not only in matters that might arguably be regarded as strictly within the province of anaesthesia, but also in respect of basic pharmacology. The same House Officers were also questioned as to the necessity for various basic pre-operative investigations prior to six everyday surgical procedures. This demonstrated a marked propensity for House Officers to overinvestigate patients as compared to the requirements of practising anaesthetists. The discrepancy was most marked with respect to pre-operative chest X rays. However, considerable disparity was also demonstrable amongst a group of experienced anaesthetists as to their requirements for pre-operative investigations. Permitting students greater exposure to anaesthesia in the undergraduate curriculum could go a long way towards improving this situation. PMID- 1616093 TI - Isosorbide dinitrate spray. Attenuation of cardiovascular responses to laryngoscopy and intubation. AB - We evaluated the efficacy of isosorbide dinitrate buccal spray (Isomack) in attenuating the cardiovascular response to laryngoscopy and tracheal intubation in 60 patients undergoing elective surgery under general anaesthesia. Patients were allocated to one of three groups of 20 patients each. Group 1 patients were administered placebo buccal spray 90 s before induction of anaesthesia. Groups 2 and 3 had isosorbide dinitrate spray 30 and 90 s before induction of anaesthesia. Systolic, diastolic and mean arterial pressures and heart rate were monitored. After the spray, group 3 patients had a significant decrease in systolic arterial pressure (p less than 0.01). At 1 min after intubation, systolic, diastolic and mean arterial pressures showed a significant increase in group 1 patients (24.9 mmHg, 14.2 mmHg and 18.7 mmHg respectively). In contrast, groups 2 and 3 showed a significant decrease in these parameters (p less than 0.01). Although significant tachycardia was present following intubation in all the three groups, the degree of tachycardia was greater in groups 2 and 3 (p less than 0.01). PMID- 1616094 TI - The laryngeal mask--a modification in its use and design. PMID- 1616095 TI - Use of the laryngeal mask airway in the presence of a bleeding diathesis. PMID- 1616096 TI - Laryngeal mask misplacement--causes, consequences and solutions. PMID- 1616097 TI - Use of the laryngeal mask airway during magnetic resonance imaging. PMID- 1616098 TI - Is clonidine an anaesthetic in man? PMID- 1616099 TI - Psychogenic seizures after general anaesthesia. PMID- 1616100 TI - A possible complication with a sheath introducer. PMID- 1616101 TI - The Oxford Miniature Vaporizer at high temperatures--evaluation of an external bypass. PMID- 1616102 TI - Secondary transfer of patients. PMID- 1616103 TI - A serious complication of minitracheotomy. PMID- 1616104 TI - Expiratory obstruction from coincidence of sizing. PMID- 1616105 TI - Anaesthetic techniques and trainee anaesthetists. PMID- 1616106 TI - Pain relief following dental extraction. PMID- 1616107 TI - Craniotomy and PEEP. PMID- 1616108 TI - Propofol and abreaction. PMID- 1616109 TI - Airway maintenance for short ophthalmological procedures in children. PMID- 1616110 TI - VCO2 following tourniquet deflation. PMID- 1616111 TI - A case of malignant hyperthermia? PMID- 1616112 TI - Red rubber Robertshaw tubes. PMID- 1616113 TI - [Speaking for myself]. PMID- 1616114 TI - [The effect of muscle relaxants on masseter tone. An experimental study in an MH susceptible swine model]. AB - Malignant hyperthermia (MH) may occur, when a genetically predisposed individual or pig (MHS) is exposed to triggering agents. The increase in free, ionized sarcoplasmic calcium inducing the vicious circle of MH is believed to result from calcium-induced release with volatile anaesthetics, and from depolarization induced calcium release with succinylcholine (SCH). The administration of SCH to susceptible humans or pigs frequently produces an increase in masticatory muscle tone. This hitherto ill-defined phenomenon is referred to as "masseter spasm" (MS). We have attempted to elucidate the pathophysiology of MS in a porcine model. METHODS. After the protocol had been approved by the state authorities, 6 MHS pigs were investigated. The pigs were mixed breeds (German Landrace and Dutch Pietrain) and were 9 +/- 1 weeks old with an average body weight of 25.5 kg. Premedication consisted of intramuscular injection of azaperone, 7.5 mg.kg-1. Anaesthesia was induced with piritramide, 1.2 mg.kg-1, administered via a cannulated ear vein. Subsequent to laryngoscopic endotracheal intubation, neuromuscular blockade was achieved with 4 mg pancuronium. Ventilation was set at 12 breaths per minute and adjusted to maintain an end-tidal CO2 concentration of 4.7% by adapting the tidal volume (PhysioFlex). Anaesthesia was maintained with piritramide, 2.25 mg.kg-1.h-1, pancuronium, 0.4 mg.kg-1.h-1, and N2O (60% in O2). Instrumentation included an arterial line, a central venous line, and a fiberoptic pulmonary artery catheter (Oximetrix). Masticatory muscle tone (MMT) was assessed with an intermolar balloon, connected to a pressure transducer and calibrated to zero prior to SCH administration. As a reference variable for effects produced by SCH, intraocular pressure (IOP) was measured manometrically in the anterior chamber. After stabilization of haemodynamic variables, the neuromuscular blockade was allowed to wear off. After recovery of the evoked masseter electromyogram, a paralyzing dose of pancuronium was administered (0.5 mg.kg-1). When paralysis was complete, SCH was administered (1.5 mg.kg-1), followed a few minutes later by dantrolene infusion (5 mg.kg-1 over 10 min). RESULTS. The administration of SCH was followed by clinically unequivocal MH episodes in all pigs, indicated by an increase in oxygen uptake (VO2; PhysioFlex; Fig. 1) and end-tidal CO2 concentration and a decrease in oxygen saturation of mixed venous blood (svO2; Fig. 2). Despite complete neuromuscular blockade (monitored with EMG), SCH produced an increase in MMT in all pigs which was reversed by dantrolene (Fig. 3). The time course of MMT paralleled that of IOP, suggesting a similar underlying mechanism. DISCUSSION. Succinylcholine is a trigger of MH in susceptible individuals; onset of the syndrome may be associated with "masseter spasm". SCH increases extraocular muscle tone, probably by means of stimulating multiply innervated fibers; the resulting IOP increase is not prevented by competitive neuromuscular blockade. The existence of multiple innervated fibers has also been shown in muscle spindles in the deep layers of the masseter, with their stimulation resulting in elevation of the jaw. We speculate that the increases in MMT and IOP observed in this study reflect the same process, i.e. a motor response, initiated by SCH-induced stimulation of the intramyocellular contractile system of multiply innervated muscle fibers, that is independent of neuromuscular transmission. Triggering of MH with SCH despite complete neuromuscular blockage suggests a mechanism other than depolarization induced calcium increase. And, for the semantics, according to neurological terminology MS should be referred to as contracture not as spasm. PMID- 1616115 TI - [Droperidol versus metoclopramide. Prevention of emesis following strabismus surgery in children]. AB - Vomiting after strabismus surgery is a major problem that remains as yet unsolved, especially in children. Droperidol and metoclopramide, both known as powerful antiemetic drugs, were compared in this study. METHODS. One hundred ASA class I and II children ranging from 3 to 10 years of age were studied in a double-blind, randomised fashion. They were assigned to three groups: group D (n = 33) received 0.075 mg/kg droperidol, group M (n = 33) 0.15 mg/kg metoclopramide, and group N (n = 34) 0.1 ml/kg NaCl i.v. upon arrival in the post anaesthesia recovery room (PARR). After oral premedication with 0.4 mg/kg midazolam, anaesthesia was induced via a face mask by inhalation of halothane, nitrous oxide, and oxygen. Barbiturates, atropine, and succinylcholine were not used; 0.05 mg/kg vecuronium was given to facilitate intubation. Gastric contents were aspirated by a gastric tube at the end of the operation. Vomiting and retching were recorded for 24 h; recovery from anaesthesia was assessed by a modified Steward score. RESULTS. The three groups were comparable regarding age, body weight, duration of anaesthesia, number of repaired eye muscles, and occurrence of the oculocardiac reflex (OCR). During the first 24 h postoperatively 21/33 (64%) patients of group D vomited, 24/33 (73%) of group M, and 33/34 (97%) of group N. The differences between groups D and N and between M and N were significant (P less than 0.01); comparison of groups D and M showed no statistical significance. Droperidol was more effective in reducing severe vomiting. Of the group N children, 47% vomited more than 6 times in 24 h compared to 18% of group M and 0% of group D. Age, sex, duration of anaesthesia, number of repaired eye muscles, and occurrence of the OCR had no influence on postoperative vomiting. Despite being administered at the end of the operation, droperidol did not prolong the patients' stay in the PARR. The post-anaesthetic scores for group D children were only slightly lower compared to groups M and N. CONCLUSIONS. Droperidol (0.075 mg/kg) and metoclopramide (0.15 mg/kg) both reduce postoperative vomiting after strabismus surgery. Droperidol seems to be more effective in reducing severe vomiting. Postoperative sedation after droperidol was not a major problem in our experience. PMID- 1616116 TI - [The integration of thoracic epidural anesthesia into anesthesia for intra abdominal surgery]. AB - Upper abdominal and thoracic surgeries require efficient pain management. The complications of postoperative analgesia include respiratory depression and--when choosing the epidural route--possible damage to the spinal cord by infection, trauma, or bleeding. Therefore, thoracic epidural analgesia may appear to be too risky and is frequently cancelled although many studies have shown its excellent efficacy. Controlled studies comparing thoracic epidural analgesia to lumbar epidural analgesia or intravenous analgetic regimens with special regard to the patient's outcome are contradictory. To make the preoperative decision on the method of pain control more rational, we studied catheter-related complications from 2056 thoracic epidural catheters used for intra- and postoperative analgesia retrospectively (n = 1002) and prospectively (n = 1054) over a 5 1/2-year period. In all patients the thoracic epidural catheter was inserted preoperatively using local anaesthesia, in most cases by the paramedian approach between level T 5/6 and T 8/9. During the clinical course of all patients there were no clinical signs of any epidural bleeding or infection. Neurological complications caused by the epidural catheter did not occur. Seven patients (0.035%) experienced radicular pain that disappeared after removal of the catheter or interruption of the puncture, respectively. A primary perforation of the dura mater was noticed in 0.5% of cases retrospectively and 1.23% prospectively. Respiratory depression following epidural application of 0.3 mg buprenorphine was seen in 1 patient (0.05%). Continuous analgesia with local anaesthetics and/or opioids applied epidurally by a thoracic catheter was performed on the peripheral ward (n = 829, 40%) if close monitoring of the neurological status as well as rapid diagnosis of any painful paraesthesia or paraplegia was possible. PMID- 1616117 TI - [A noncardiac pulmonary edema following aortocoronary bypass surgery. Diagnosis and therapy based on a case report]. AB - Noncardiac pulmonary edema can occur not only after cardiac surgery with cardiopulmonary bypass but also after noncardiac operations. This so-called transfusion-related acute lung injury (TRALI) has been attributed to the transfusion of homologous blood and plasma. In the presence of normal left ventricular function an acute increase in pulmonary capillary permeability leads to massive protein-rich pulmonary edema, reduced pulmonary function, and intravascular hypovolemia. This may be caused by leukocyte antibodies. Signs and diagnostic and therapeutic procedures are discussed with reference to a case report. PMID- 1616118 TI - [Subdural and epidural hematomas following epidural anesthesia. A literature review]. AB - Of 434 cases of epidural, subdural, and intracranial haematomas published in the last 2-3 decades, 61 had developed following spinal, epidural or caudal anaesthetic procedures; 29 haematomas were around the spinal cord and 32, within the cranium. The most frequent secondary cause of this complication was pre-, intra-, or postoperative administration of drugs influencing blood coagulation. Simultaneous traumatic and haemorrhagic punctures may favour the development of a haematoma. The most common primary symptom of lumbothoracic haematomas was back pain with and without radicular symptoms, while intracranial haematomas were predominantly accompanied by persistent headache. Continuous postoperative follow up of such patients is essential. Postoperative results of laminectomies for lumbothoracic haematomas has been found to on the time interval between the first symptoms and the start of surgery. If surgery is performed within 8 h after the onset of paraplegia the prognosis is relatively good. Compared with the frequency of spinal, epidural, and caudal anaesthetic procedures throughout the world, haematomas of the lumbothoracic or cranial region are extremely rare complications. PMID- 1616119 TI - [Total spinal anesthesia. A complication of lumbar catheter peridural anesthesia for postoperative analgesia]. AB - A case of secondary subarachnoidal dislocation of a lumbar epidural catheter is reported. A 76-year-old female underwent resection of the sigmoid colon. In order to provide postoperative analgesia, an epidural catheter was inserted between the 3rd and 4th lumbar interspaces prior to induction of anaesthesia. Aspiration tests were negative twice and a test dose of 4 ml 0.5% bupivacaine produced no signs of anaesthesia. Thereafter, the operation was performed under balanced general anaesthesia. Prior to the end of surgery a total of 14 ml bupivacaine 0.5% was administered without significant cardiovascular depression. At the time of extubation the patient was awake and free of pain. There was no sign of respiratory depression or paralysis of the upper extremities. Three hours later in the recovery room the patient complained of pain. After a negative aspiration test 14 ml bupivacaine 0.25% was injected. Thirty minutes after injection apnea and cardiac arrest occurred. Resuscitation was immediately started, resulting in quick restoration of circulation and restitutio ad integrum. Aspiration at this time showed cerebrospinal fluid. The latency of the onset of total spinal anaesthesia and the rapid restoration of stable vital functions, was astonishing. It is essential to observe the common precautions such as an aspiration test without a filter, administration of a test dose, and titration of the injected amount each time the anaesthetic agent is applied via an epidural catheter. PMID- 1616120 TI - [Ambulatory epidural analgesia in patients with tumors. An outmoded technique?]. AB - In 35 of 316 patients suffering from severe cancer pain, an epidural catheter was placed for continuous morphine application. Indications for epidural opiates included failure of pain relief with oral morphine, severe side effects with oral administration, and contraindications for oral morphine, e.g., ileus. METHODS. The epidural catheter was inserted in the lumbar, thoracic or cervical region, according to the main localization of pain. A silicon catheter with a Dacron cuff (4.2 F Broviac Davol, Cranston, R.I.) was connected and tunneled subcutaneously to a distant exit on the lateral chest wall (Fig. 2). A portable morphine pump (CADD-PCA Pharmacia Deltec) was connected to the externalized catheter. The morphine was infused continuously at a basic rate. It could be increased to a programmed limit by additional boli determined by the patients themselves. Thirty patients were treated as outpatients. RESULTS. The mean duration of treatment was 101 (10-333) days. The daily dose of morphine ranged from 9 to 200 (33) mg at the beginning of therapy, and from 20 to 288 (88) mg at the end of treatment. In 27 patients (77%) epidural morphine administration proved to be a valuable method of pain control (Fig. 3). Even in most cases of tolerance to oral morphine, especially in patients suffering from pain of neuropathic origin, pain control was adequate. There were no cases of continuous loss of effectiveness of continuous loss of effectiveness or development of tolerance (Fig. 5). The epidural morphine dosage depended on the character and intensity of pain and its responsiveness to epidural opiates. Technical complications were noticed in 6 patients (17%), and fairly mild side effects of epidural morphine occurred in 20% of the patients for a limited time. CONCLUSIONS. The technique described is a simple and convenient method for long-term treatment of cancer patients with epidural morphine. There was no need for more invasive procedures, such as intrathecal or intraventricular morphine administration, in this group of patients in whom no pain relief had been achieved with oral morphine administration. PMID- 1616121 TI - [The usefulness of the laryngeal mask in ambulatory anesthesia. An evaluation of 200 cases of ambulatory anesthesia]. AB - We studied the value of Brain's laryngeal mask on 200 patients undergoing ambulatory operations under general anaesthesia using propofol and alfentanil. Continuous registration of maximal airway pressure and pulse oximetry were carried out. The operations were performed mainly in the following four specialities: urology, general surgery, gynaecology, and ophthalmology. The mean operation time was 39 min (6-82 min). All patients belonged to ASA groups I-III. No patient was premedicated. We encountered no difficulties in introducing the mask using the technique described by Brain except in one 6-year-old boy with hypertrophic tonsils in whom it was impossible. Insufficient sealing of the trachea occurred in a 29-year-old woman with thyroid hypertrophy. In most patients (70%) the oxygen saturation (spO2) could be maintained above 95%; only 6 (2%) showed an spO2 value of less than 90%. Peak inspiratory pressures--a measure of tight fitting of the mask--are shown in Table 2. Laryngospasm occurred in 2 children who had inhalation inductions with halothane. This complication was never seen after induction with propofol. The most important positive finding was that relaxant drugs became largely unnecessary after we started working with the mask, which reduced postoperative recovery time as well as costs. CONCLUSION. We consider the laryngeal mask to be not only an important new technique, but in combination with propofol and alfentanil the method of choice for ambulatory anaesthesia in day-case surgery. PMID- 1616122 TI - [Transfusion related lung injury--hypothesis or clinical reality? Comments on the article by U. Schirmer et al. A noncardiac pulmonary edema following aortocoronary bypass surgery]. PMID- 1616123 TI - [Paralysis due to carbohydrates. The role of hypernatremia]. PMID- 1616124 TI - Determination of human serum alcohol dehydrogenase using isozyme-specific fluorescent substrates. AB - Both class I and class II alcohol dehydrogenase (ADH) activities are present in human serum. The contribution of each class can be measured using two class specific, fluorogenic substrates, 4-methoxy-1-naphthaldehyde and 6-methoxy-2 naphthaldehyde. The former is highly selective for class I isozymes, especially those containing alpha or gamma subunits, whereas class II (pi) ADH preferentially reduces the latter. Selective inhibition of class I ADH by 4 methylpyrazole further increases the specificity. Specificity, accuracy, and precision of the assay for serum measurements have been determined. The activity of class I ADH in normal human serum is below the limit of detection of this method, i.e., less than 1.0 nM/min. The activity of class II ADH in normal individuals is 15 +/- 5 nM/min. In some patients values as high as 2100 nM/min are observed for class I, but in all instances, the amount of class II found was higher than that of class I ADH. PMID- 1616125 TI - Instrumentation for the breath-by-breath determination of oxygen and carbon dioxide based on nondispersive absorption measurements. AB - This paper describes the development and evaluation of instrumentation for the breath-by-breath determination of oxygen and carbon dioxide in respiratory gases. The method is based on nondispersive absorption and uses the 145-nm absorption band for detection of oxygen and the 4.3-micron band for detection of carbon dioxide. A xenon discharge lamp with a sharp band at 147 nm was chosen as the source for the determination of oxygen, and a carbon dioxide discharge lamp with a sharp band at 4.3 micron was chosen for determination of carbon dioxide. A vacuum photodiode was used as the detector for oxygen, and a photoconductive cell with a built-in interference filter was used for detection of carbon dioxide. Plots of absorbance (A) vs concentration (C, %) were linear for oxygen and were nonlinear for carbon dioxide. Typical least-squares calibration equations were A = 0.020C + 0.02 for oxygen (0-100%) and A = 0.0012C2 + 0.050C + 0.008 for carbon dioxide (0-8%). Comparisons of computed (y) vs prepared (x) values for the concentrations given above were linear for both gases, yielding y = (1.00 +/- 0.01)x - 0.13 +/- 0.73 for oxygen and y = (1.07 +/- 0.02)x - 0.04 +/- 0.06 for carbon dioxide. The standard deviations were 1.2% at 50% oxygen and 1.5% at 4% carbon dioxide. Records are presented to illustrate breath-by-breath monitoring of these gases in a healthy subject. PMID- 1616126 TI - Separation of fluoride from fluoroelastomers by diffusion in test tubes. AB - The conventional procedure for separation of fluoride as trimethylfluorosilane in Conway diffusion cells involves the use of grease for sealing the cell and also for closing the hole in the lid drilled for introduction of hexamethyldisiloxane. We have developed a simpler procedure in which diffusion is carried out in 5-mL test tubes without the use of grease. Results of analysis of fluoride following diffusion from water, urine, and bone samples are in excellent agreement with those obtained by other procedures not involving diffusion. Separation of fluoride from partly and fully cured fluoroelastomers is achieved by first grinding the samples in a liquid nitrogen mill and then using methyl ethyl ketone as an adjuvant to perchloric acid employed in the diffusion procedure. PMID- 1616127 TI - Determination of phospholipids from pulmonary surfactant using an on-line coupled silica/reversed-phase high-performance liquid chromatography system. AB - A basic normal-phase HPLC separation of phospholipids can be improved by introducing a limited contribution of solvophobic retention. For this purpose, the effect of an additional alkylsilica (C18) column of variable length coupled in series with a silica column was investigated. With increasing percentage of reversed phase in this system, the retention of phosphatidylglycerol increased. Phosphatidylinositol and phosphatidylserine were separated into molecular species. The "selective retention" defined in this study permits an evaluation of the solvophobic retention of phospholipids in the coupled system. An alternative column switching procedure is used for specific applications of the biphasic separation on chosen phospholipids. With this system, determination of phosphatidylglycerol and six other phospholipids from pulmonary surfactant could be performed. PMID- 1616129 TI - Empirical procedure that uses molecular structure to predict enantioselectivity of chiral stationary phases. AB - A total of 121 racemic compounds were separated in the normal-phase mode on a (S) (1-naphthylethyl)carbamoylated beta-cyclodextrin (S-NEC-beta-CD) bonded phase and 74 on the R equivalent (R-NEC) chiral stationary phase (CSP). All compounds are of the type that have four substituents on a stereogenic center, rather than an "axis of chirality". It is shown that the binary solvent pair used as the mobile phase has a significant influence on chiral recognition. However, the proportions of the components of a specific pair have little effect. From the results, the individual contributions to chiral recognition by these CSPs were estimated for 81 different substituents of the stereogenic center. Varying the arrangement of these 81 substituents could produce over 1.6 million compounds. Hydrogen was chosen as the reference substituent and was assigned a 0 cal/mol free energy. The chiral recognition increased when sp2-hybridized carbons were connected to the stereogenic center. Conversely, sp3-hybridized carbons decreased the enantioselectivity. Amido groups increased the chiral recognition, especially when associated with pi-acid (3,5-dinitrobenzoyl) or pi-basic (naphthyl) groups. This approach does not allow one to know which enantiomer elutes first. However, the "substituent energy" list for chiral compounds can be used to obtain an estimated value for the enantioselectivity of a compound by adding the energy contributions of the four substituents connected to the stereogenic center. In this way one can predict a priori whether or not a compound will separate on a CSP and estimate its separation factor (alpha). Theoretically, this approach can be used for most CSPs, provided a sufficient data base is generated on them. PMID- 1616128 TI - Effects of analyte velocity modulation on the electroosmotic flow in capillary electrophoresis. AB - Modulation of the electroosmotic flow in capillary zone electrophoresis by modulation of the driving voltage gives rise to a flow profile that changes between laminar and flat profiles. The changing flow profile induces a radial movement of sample species to and from the capillary surface. The induced sample concentration gradient can be monitored by carefully probing the capillary surface. The resulting signal is a derivative of the normal-shaped peak. Derivative-shaped peaks can be observed with cations, but not with anions. Anions are unable to approach the double-layer region and therefore are unaffected by the modulation process. PMID- 1616130 TI - Preconcentration of dopamine by uphill transport across an ion-exchange membrane. AB - The transport of dopamine from samples in which it is in the cationic form across a cation-exchange membrane into a receiver electrolyte occurred against its concentration gradient under two conditions. With receiver electrolytes at pH values below the pKA1 of dopamine, the transport was by Donnan dialysis. With the pH above the pKA1, the neutralization of protonated dopamine at the membrane receiver interface sustained the diffusion gradient of the dopamine cation across the membrane phase, thereby allowing the analytical concentration of this species to increase above that of its concentration in the sample. When 0.25 M RbCl, 0.5 mM LaCl3 mixtures in the pH range 3.0-7.0 comprised the receivers, preconcentration factors of 20 were achieved with a 15-min dialysis across a tubular cation-exchange membrane. Under identical conditions except with a pH 10 receiver, the preconcentration factor was 22. The former condition results in Donnan dialysis whereas the transport mechanism at pH 10 is sustained passive diffusion. In contrast to Donnan dialysis, transport rates under sustained passive diffusion conditions are independent of ionic strength over a wide range; for example they are constant for samples containing up to 0.17 M KH2PO4 at pH 4.6. PMID- 1616131 TI - Homogeneous mechanism of ascorbic acid interference in hydrogen peroxide detection at enzyme-modified electrodes. PMID- 1616132 TI - An anatomical investigation of the muscles of the pelvic outlet in iguanas (Iguanidae Iguana iguana) and varanus (Varanidae Varanus (dumerillii)) with special reference to their nerve supply. AB - Five pelvic halves from three male iguanas (Iguanidae Iguana iguana) and two pelvic halves from one male varanus (Varanidae Varanus (dumerillii)), were dissected in order to obtain detailed data on the relationship of the lumbosacral plexus and the muscles of the pelvic outlet. According to the positions of the passage of the metazonal nerves, the nerves can be divided into three groups: 1) the nerves passing dorsal to the caudofemoralis muscle, 2) the nerves passing between the caudofemoralis and the caudoischiadicus major, 3) the nerves passing ventral to the caudoischiadicus major. In consideration of the sites of origin from the lumbosacral plexus, a stratificational analysis can be proposed; group 1 arises craniodorsal to group 2, and group 3 caudoventral to group 2. It is suggested that the pelvic outlet muscles (caudofemoralis, quadratus caudae, obliquus cloacae, transversus cloacae profundus, retractor penis, caudoischiadicus major, and the caudoischiadicus minor) are derived from the ventral muscles of the posterior limb, and have moved caudally concomitant with the caudal migration of the cloaca. PMID- 1616133 TI - Neurochemical anatomy of the mammalian spinal cord: functional implications. PMID- 1616134 TI - Anesthesia and myocardial ischemia: the gains of the past have largely come from control of myocardial oxygen demand; the breakthroughs of the future will involve optimizing myocardial oxygen supply. PMID- 1616135 TI - Effect of chloride transport blockade on the MAC of halothane in the rat. AB - There is a growing evidence that central nervous system chloride transport via gamma-aminobutyric acid (GABAA) related Cl- conductance or Cl-/HCO3- exchange affects anesthetic requirements. To delineate the effects of GABAA-related Cl- conductance blockade versus Cl-/HCO3- exchange inhibition, we determined the change in minimum alveolar anesthetic concentration (MAC) of halothane in rats after intracisternal infusion of 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS). DIDS inhibits Cl-/HCO3- exchange transport in concentrations greater than 1 microM and in GABAA-related Cl- channels in concentrations greater than 0.1 mM. After control MAC determination, rats were given intracisternal mock cerebrospinal fluid (n = 6), 1.0 microM DIDS (n = 8), or 1 mM DIDS (n = 8) at a rate of 2 microL/min for 30 min. Mock cerebrospinal fluid did not change the MAC of halothane. The MAC of halothane increased significantly (P less than 0.001) from 0.96% +/- 0.02% to 1.11% +/- 0.03% (mean value +/- SEM) with 1 microM DIDS and from 0.94% +/- 0.02% to 1.16% +/- 0.04% with 1 mM DIDS. The increases in MAC with 1 microM and 1 mM DIDS were not statistically different. This suggests that Cl-/HCO3- exchange inhibition increases halothane requirements, whereas GABAA related Cl- channel blockade does not. PMID- 1616136 TI - Isoflurane anesthesia prevents unconscious learning. AB - We investigated whether greater than or equal to 0.6 minimum alveolar concentration (MAC) of isoflurane suppresses learning of information presented verbally. Preoperatively, we asked 45 healthy patients (aged 23-58 yr) undergoing elective surgery 15 general knowledge questions designed to arouse their curiosity. They were told that they would be given the answers during anesthesia. Anesthesia was induced with isoflurane and nitrous oxide (25 subjects also received 1.1 +/- 0.6 mg/kg of propofol). The trachea was intubated with the aid of vecuronium (0.07 mg/kg IV). Isoflurane in oxygen was given to provide 0.6 MAC before and 1.0 and 1.4 MAC during surgery. After 10 min at each of two of the three MAC levels, the answers were given to five of the questions. At the remaining concentration, patients received a message to either touch an ear (n = 30) or keep their arms still (n = 15) during the postoperative interview. Twenty four hours later, patients were asked whether they recalled intraoperative events. They were then asked to answer the 15 questions, choosing from five possible answers to each, one of which was correct. The number of times each patient touched an ear during this interview was noted. No patient consciously recalled events during anesthesia. The number of questions answered correctly postoperatively did not differ according to whether the answers had been provided during anesthesia (at any isoflurane concentration) or had not been provided (control questions). The number of ear-touches postoperatively did not differ between those who had and had not received the intraoperative message encouraging ear-touching.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616137 TI - Oxygen consumption and carbon dioxide elimination after release of unilateral lower limb pneumatic tourniquets. AB - Oxygen consumption (VO2), carbon dioxide elimination (VCO2), and respiratory exchange ratio (RQ) were continuously measured in 15 male and 15 female adults during knee surgery, with the leg exsanguinated by an inflatable tourniquet around the thigh. Arterial blood was also intermittently sampled for blood gas analysis, electrolytes, and lactate content before and after tourniquet deflation. There was a significant increase in VO2 and VCO2 after tourniquet deflation, which was more pronounced in the male (aged 29.5 +/- 14.8 yr, mean +/- SD) than the female (aged 56.9 +/- 15.6 yr) patients, both in terms of maximal increase (P less than 0.001) and percent of increase from values before deflation (P less than 0.001 and P = 0.01). The body weights and tourniquet inflation times were not significantly different between the male and female patients. Excess VO2 (O2 debt) and excess VCO2 over 12 min after deflation of the tourniquet were also significantly higher for male (593.5 +/- 222.9 mL and 714.9 +/- 463.8 mL, respectively) than for female patients (302 +/- 73.3 mL and 196 +/- 162.22 mL, respectively; P less than 0.01). There was no correlation between the duration of tourniquet inflation time and peak increase in VO2, peak increase in VCO2, and O2 debt over 12 min after deflation of the tourniquet; however, tourniquet time was weakly correlated with excess VCO2 over 12 min after tourniquet deflation (r = 0.55, P = 0.002). There was a significant decrease in pHa (P less than 0.001) from release of PaCO2 and lactate after tourniquet deflation. Plasma potassium levels also increased significantly after tourniquet release (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616138 TI - Coagulopathy after reinfusion of autologous scavenged red blood cells. PMID- 1616139 TI - Accidental overdose of systemic morphine during intended refill of intrathecal infusion device. PMID- 1616140 TI - Unsuccessful interpleural analgesia in a patient with mesothelioma. PMID- 1616141 TI - Upper airway obstruction and infant botulism. PMID- 1616142 TI - Job's syndrome: an unusual response to a common drug. PMID- 1616143 TI - Mass spectrometers and infrared gas analyzers interpret bronchodilator propellants as anesthetic gases. PMID- 1616145 TI - Isolated masseter muscle spasm versus generalized rigidity? PMID- 1616144 TI - Masseter muscle spasm and the diagnosis of malignant hyperthermia susceptibility. PMID- 1616146 TI - Ventilatory effects of clonidine. PMID- 1616147 TI - An unusual cause of nasogastric tube obstruction. PMID- 1616148 TI - Relief of pain by ketorolac or alcohol? PMID- 1616149 TI - Effects of adenosine after coronary artery bypass surgery. PMID- 1616150 TI - Venous air embolism during spinal instrumentation and fusion in the prone position. PMID- 1616151 TI - Venous air embolism during spinal instrumentation and fusion in the prone position. PMID- 1616152 TI - An aid to oral intubation in patients with potential cervical spine injuries. PMID- 1616153 TI - Not all E cylinders were created equal. PMID- 1616155 TI - Peer-reviewed anesthesiology journals and research. PMID- 1616154 TI - Anesthetic drugs and the emergency department: one teaching institution's response. PMID- 1616156 TI - Mechanisms of renal hemodynamic impairment during infrarenal aortic cross clamping. AB - Infrarenal aortic cross-clamping is associated with impairment of renal hemodynamics due to vasoconstriction, the mechanism of which remains under debate. To assess the renal effect of two potent renal vasodilators (enalapril, a converting enzyme inhibitor, and nicardipine, a calcium antagonist), 24 patients scheduled for reconstructive aortic surgery were randomly allocated to one of three treatment groups (n = 8 each) and received either a placebo, nicardipine, or enalapril. Anesthesia consisted of flunitrazepam, fentanyl, pancuronium, and, occasionally, droperidol. Although aortic cross-clamping was associated with no change in mean arterial blood pressure, decreased cardiac output and increased systemic vascular resistance occurred in control patients (33% and 43%, respectively, both P less than 0.05 versus baseline) and nicardipine-treated patients (51.7% and 67.7%, respectively, both P less than 0.05 versus baseline); however, changes in cardiac output and systemic vascular resistance failed to reach significance in enalapril-treated patients. Glomerular filtration rate (technetium 99-diethylenetriaminepentacetic acid clearance) and effective renal plasma flow (iodo-Hippuran 131 clearance) decreased for the duration of aortic cross-clamping in control patients (42.9% and 18.5%, respectively, both P less than 0.05 versus baseline) and enalapril-treated patients (34.0% and 38.1%, respectively, both P less than 0.05 versus baseline), but no change was observed in nicardipine-treated patients. These results suggest that the reninangiotensin system is not an important determinant of the renal vasoconstriction associated with aortic cross-clamping. In contrast, renal dysfunction may be alleviated by the dihydropyridine derivative nicardipine, which probably acts at the level of the preglomerular resistance vessels. PMID- 1616157 TI - Effects of fentanyl on alpha-aminoisobutyric acid transfer across the blood-brain barrier. AB - The effect of fentanyl on the transfer of small hydrophilic molecules across the blood-brain barrier was studied in rats by measuring the blood-brain transfer coefficient (Ki) and the regional cerebral blood flow (rCBF) and by calculating the capillary permeability-surface area product. In the control group (n = 14), after a femoral artery and vein were catheterized under isoflurane anesthesia, the rats were allowed to remain awake for 1.5 h before measuring Ki (n = 8) using intravenous 14C-alpha-aminoisobutyric acid or rCBF (n = 6) using 14C iodoantipyrine. In the fentanyl groups, rats were injected with 25 micrograms/kg (low (n = 6) or 100 micrograms/kg (high dose) of fentanyl (n = 14), followed by a continuous infusion at a rate of 50 or 200 micrograms.kg-1.h-1, respectively. Their lungs were mechanically ventilated. The Ki (low dose, n = 6; high dose, n = 8) and rCBF (high dose, n = 6) were measured 1 h after fentanyl infusion. The Ki was lower in 9 of 13 brain regions in the low-dose fentanyl group and in 7 of 13 brain regions in the high-dose fentanyl group than in the control animals. The average value of Ki in all the brain regions was 8.6 +/- 4.6 microL.g-1.min-1 in the control group, 5.2 +/- 2.9 microL.g-1.min-1 in the low-dose fentanyl group, and 5.7 +/- 2.9 microL.g-1.min-1 in the high-dose fentanyl group. High-dose fentanyl did not significantly affect rCBF in any brain region studied. The value of the regional permeability-surface area product was similar to the corresponding regional Ki in the groups studied. In conclusion, fentanyl decreased the transfer of small hydrophilic molecules across the blood-brain barrier, as demonstrated by a decreased Ki and permeability-surface area product, without significant changes in rCBF. PMID- 1616158 TI - Evaluation of the endotracheal intubating conditions of rocuronium (ORG 9426) and succinylcholine in outpatient surgery. AB - The time-course of action and tracheal intubating conditions of rocuronium and succinylcholine under intravenous anesthesia with propofol, alfentanil, and nitrous oxide were studied in 30 patients undergoing outpatient surgery. The neuromuscular effects of both drugs were quantified by recording the indirectly evoked twitch response of the adductor pollicis muscle after ulnar nerve stimulation (0.1 Hz, 0.2 ms supramaximal stimuli). Patients were given either 0.6 mg/kg rocuronium (n = 20) or 1 mg/kg succinylcholine (n = 10) intravenously. Sixty seconds after the administration of the muscle relaxant, the trachea was intubated and the intubating conditions were scored by a "blinded" assessor. Intubating conditions were not different (P = 0.34) between the rocuronium and succinylcholine groups. The onset and duration of neuromuscular blockade were shorter with succinylcholine than with rocuronium. The depression of the twitch response to 5% of control value occurred in 0.8 +/- 0.1 min with 1 mg/kg succinylcholine and 1.2 +/- 0.5 min with 0.6 mg/kg rocuronium (P less than 0.01). The recovery of the twitch response to 25%, 75%, and 90% of its control value was shorter after succinylcholine (P less than 0.001) and occurred at 8.1 +/- 2.6, 10.3 +/- 3.9, 11.3 +/- 4.6 and 25.3 +/- 5.0, 33.1 +/- 5.9, 36.1 +/- 6.3 min after succinylcholine and rocuronium, respectively. Also the time required for spontaneous recovery from 25% to 75% of the control twitch response was significantly shorter (P less than 0.001) after succinylcholine (2.2 +/- 1.4 min) than after rocuronium (7.8 +/- 2.1 min). It is concluded that in spite of the pharmacodynamic differences between succinylcholine and rocuronium, the intubating conditions after administration of both compounds are similar and develop at the same rate. PMID- 1616159 TI - Halothane relaxes previously constricted human epicardial coronary artery segments more than isoflurane. AB - To compare the vasodilatory effects of isoflurane versus halothane on coronary arteries in vitro, we studied the capacity of isoflurane and halothane to relax resting and previously constricted human coronary artery segments with use of in vitro tension recording. Human epicardial coronary artery segments (1.5-2.0 mm outside diameter) were obtained from hearts excised from recipient patients at time of heart transplantation. The effects of 0.5%, 1.0%, 2.0%, and 3.0% isoflurane or halothane on resting coronary artery segments stretched to their optimal resting tension were determined. Next, after removal of anesthetic from the bathing solution, the segments were constricted with K+ (60 mM), and this contraction was allowed to plateau. The arteries were then again exposed to isoflurane or halothane at 0.5%, 1.0%, 2.0%, and 3.0% concentrations. Isoflurane and halothane had no effect on noncontracted coronary artery segments stretched to their optimal resting tension. Halothane caused significant relaxation of K(+) induced (60 mM) contractions at 2.0% and 3.0% but not at lower concentrations. Isoflurane did not cause significant relaxation of K(+)-induced (60 mM) contractions at any concentration studied. Our studies indicate that under the conditions studied, isoflurane at clinically relevant concentrations is not a significant coronary dilator. PMID- 1616160 TI - Intraoperative patient-controlled analgesia: an alternative to physician administration during outpatient monitored anesthesia care. AB - Outpatients undergoing minor diagnostic and therapeutic procedures associated with intermittent discomfort are frequently given bolus injections of intravenous opioid analgesics. In a group of 80 healthy women undergoing vaginal ovum pickup procedures, we evaluated patient-controlled administration of alfentanil using a patient-controlled analgesia device (with a lockout interval of 3 min) as an alternative to conventional physician-controlled administration. The two alfentanil administration techniques were equally effective in providing intraoperative analgesia. The average alfentanil dosage requirements were 1.49 +/ 0.50 and 1.46 +/- 0.55 micrograms.kg-1.min-1 (mean +/- SD) in the physician- and patient-controlled groups, respectively. The incidence of postoperative nausea was the same in both treatment groups (8%). Even with the mandatory lockout interval, intraoperative patient-controlled administration of alfentanil was comparable to physician-controlled administration with respect to patient comfort and satisfaction during vaginal ovum pickup procedures. PMID- 1616161 TI - Efficacy of the FEF colorimetric end-tidal carbon dioxide detector in children. AB - Direct laryngoscopy and observation of endotracheal tube (ETT) passage between the vocal cords remain the criterion standard for verifying endotracheal intubation. Detection of end-tidal carbon dioxide (ETCO2) serves as an invaluable adjunct to confirm endotracheal intubation, detect inadvertent esophageal intubation, and monitor for accidental tracheal extubation. Capnography, however, is often unavailable outside the operating suite. A commercially available, disposable, colorimetric ETCO2 detector (FEF, Fenem, Inc., New York, N.Y.), in which color changes using a numerical scale semiquantitatively measure percent carbon dioxide in exhaled gases, has proved effective in confirming endotracheal intubation in adults, but has not been thoroughly investigated in children. We studied 20 otherwise healthy children, aged 6 mo to 8 yr, with simultaneous infrared and colorimetric ETCO2 measurements during elective general anesthesia to evaluate the efficacy of the colorimetric detector. Two hundred of 200 tracheally intubated positive-pressure breaths and 198 of 200 breaths under spontaneous mask ventilation demonstrated a yellow color change (color level 5 or 6), signifying an ETCO2 greater than or equal to 15 mm Hg (2.0 kPa). Repeated measures analysis of variance revealed no significant differences in infrared ETCO2 values between the two yellow color levels throughout the study period. The associations among color level, infrared ETCO2 determinations, ETT size, and ETT "leak" pressures estimated by Spearman rank correlation analysis were significant only for higher infrared ETCO2 values with higher ETT leak pressures (P less than 0.05). No complications were observed. The Fenem disposable colorimetric ETCO2 detector effectively confirms clinical signs of endotracheal intubation in children when capnography is unavailable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616162 TI - Oral midazolam in children: effect of time and adjunctive therapy. AB - The purpose of this study was to determine the influence of timing and concomitant administration of atropine and/or meperidine on the perioperative effects of oral midazolam in children. In 154 healthy children, 1-8 yr old, we studied six oral preanesthetic medication regimens according to a randomized, double-blind protocol. Group A (placebo) received 5 mL of apple juice. The other five groups received medication with apple juice to a total volume of 5 mL, 20-60 min before induction of anesthesia. Group B received atropine (0.02 mg/kg); group C received midazolam (0.5 mg/kg); group D received midazolam (0.5 mg/kg) and atropine (0.02 mg/kg); group E received meperidine (1.5 mg/kg) and atropine (0.02 mg/kg); and group F received meperidine (1.5 mg/kg), atropine (0.02 mg/kg), and midazolam (0.5 mg/kg). The sedative effect of midazolam was maximal 30 min after oral administration. Ninety-five percent of the children who were separated from their parents within 45 min after oral midazolam administration (with or without atropine) had satisfactory separation scores (vs 66% of those separated after 45 min; P less than 0.02). Midazolam-treated patients were more cooperative with a mask induction of anesthesia compared with non-midazolam-treated children (83% vs 56%). Neither atropine nor meperidine appeared to significantly improve the effectiveness of oral midazolam. No preoperative changes in heart rate, respiratory rate, or hemoglobin oxygen saturation were noted in any of the treatment groups. Finally, oral midazolam did not prolong recovery even after outpatient procedures lasting less than 30 min. In conclusion, midazolam (0.5 mg/kg) given orally 30-45 min before induction of anesthesia is safe and effective without delaying recovery after ambulatory surgery. PMID- 1616164 TI - Combination of low-dose epidural morphine and intramuscular diclofenac sodium in postcesarean analgesia. AB - Epidural morphine is used for postcesarean analgesia, and nonsteroidal antiinflammatory drugs are frequently administered to relieve uterine cramps after vaginal delivery. To assess the efficacy of a combination of low-dose epidural morphine and intramuscular diclofenac sodium in postcesarean analgesia, a double-blind, randomized study was conducted. Epidural anesthesia was given to 120 parturients who were randomly allocated into four treatment groups: group A received normal saline solution, 10 mL epidurally and 3 mL intramuscularly (IM); group B received 10 mL of epidural saline solution and 75 mg (3 mL) of diclofenac IM; group C received 2 mg of morphine in 10 mL of epidural saline solution and 3 mL of saline solution IM; and group D received 2 mg of morphine in 10 mL of epidural saline solution and 75 mg of diclofenac IM. Epidural injections were given after delivery of the placenta, and IM injections were given on arrival in the recovery room. Verbal analogue pain scores were recorded at 2, 4, 8, 12, 18, and 24 h after epidural injection. Subjective scores of overall pain relief were also recorded at 24 h. Results showed that scores of overall pain relief were significantly better in group D compared with group A, B, or C (P less than 0.05). Groups A and B required more supplemental meperidine than groups C and D. None of the subjects in group D requested supplemental analgesia. Compared with the other three groups, group D experienced a better analgesic effect for both wound pain and uterine cramping pain from 4 to 18 h (P less than 0.05). Incidence of nausea or vomiting, or both, and pruritus occurred more frequently in groups C and D compared with group A or B (P less than 0.05). No bradypnea was observed during the study period. Diclofenac alone was not effective in postcesarean analgesia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616163 TI - Vasopressor therapy for hypotension during epidural anesthesia for cesarean section: effects on maternal and fetal flow velocity ratios. AB - The purpose of this study was to identify the influence of hypotension as a result of epidural anesthesia and of its treatment with either ephedrine or methoxamine on uteroplacental and umbilical flow velocity ratios and fetal acid base status. Fifty healthy women with an uncomplicated full-term pregnancy were studied during elective cesarean section under epidural anesthesia. A method of continuously recording flow velocity waveforms was used that allowed the identification of simultaneous values of maternal and fetal Doppler indices related to events during the induction of anesthesia. In 15 patients in whom arterial blood pressure did not decrease, the uteroplacental pulsatility index (UtPI) did not change, but the umbilical pulsatility index (UmPI) decreased from a mean (95% confidence interval) of 0.98 (0.88-1.09) to 0.91 (0.82-0.99) (P less than 0.05). In 32 patients who experienced hypotension of at least 15%, the UtPI increased from 0.82 (0.76-0.89) to 1.04 (0.92-1.17) (P less than 0.01). Treatment with ephedrine had no influence on either the UtPI or UmPI, but treatment with methoxamine resulted in brief increases in the UtPI of 0.47 (0.24-0.69) during the first 5 min after its administration; the increases were brief and resolved within 2 min. The choice of vasopressor drug had no influence on the UtPI recorded just before surgery commenced (final UtPI), but those patients who experienced hypotension had significantly larger final UtPIs (1.02 (0.91-1.10)) than those who never became hypotensive (0.86 (0.72-0.99)), and this was associated with significantly increased placental hydrogen ion gradients. The choice of vasopressor drug appears to be of minor importance compared with the avoidance of hypotension. PMID- 1616165 TI - Comparison between clonidine and epinephrine admixture to lidocaine in brachial plexus block. AB - The admixture of clonidine or epinephrine to lidocaine for brachial plexus block was studied with regard to duration of block, postoperative analgesia, and plasma concentrations of lidocaine. Thirty-three patients of ASA physical status I and II received an admixture of either clonidine (150 micrograms; n = 15) or epinephrine (200 micrograms; n = 18) to 40 mL of 1% lidocaine in a randomized, double-blind fashion. Bone surgery predominated in those patients receiving clonidine and soft-tissue surgery in those receiving epinephrine (P less than 0.05). Onset and duration of block were not different between the groups. With the admixture of clonidine, fewer patients were completely pain free for greater than 12 h (13.3%) and pain scores (visual analogue scale 0-10) were higher 6 h after the block (median 4; range 0-6) than with epinephrine (61.1%; median 2; range 0-7, respectively; P less than 0.05). In patients who had received clonidine, peak plasma concentrations of lidocaine were higher (10.29 +/- 2.96 mumol/L) and occurred earlier (23.7 +/- 9.3 min; mean +/- SD) than in those treated with epinephrine (6.9 +/- 1.71 mumol/L; 72.5 +/- 56.2 min; P less than 0.05). This indicates the absence of a local vasoconstrictor effect of clonidine and implies a reduced margin of safety with regard to local anesthetic toxicity. Although clonidine does not offer advantages compared with epinephrine, it may be a useful adjunct to local anesthetics in those patients in whom the administration of epinephrine is contraindicated. PMID- 1616166 TI - Clinical pharmacokinetics of R(+)- and S(-)-mepivacaine after high doses of racemic mepivacaine with epinephrine in the combined psoas compartment/sciatic nerve block. AB - The purpose of this study was to investigate the pharmacokinetics of R(+)- and S( )-mepivacaine in 10 male patients after injection of a high dose (731 mg) of racemic R,S-mepivacaine for a combined psoas compartment/sciatic nerve block. Arterial blood samples were taken, and the plasma concentrations of the stereoisomers R(+)- and S(-)-mepivacaine were measured by means of high performance liquid chromatography (HPLC) with a Chiral AGP column. The S(-) isomer reached higher plasma concentrations than the R(+) isomer. The maximal plasma concentration (Cmax) of R(+) was 1.54 +/- 0.34 micrograms/mL, whereas that of the S(-) isomer was 2.34 +/- 0.51 micrograms/mL (P = 0.00050). The time at which Cmax was reached (Tmax) was identical for both isomers. The area under the plasma concentration-time curve from t = 0 to infinity (AUC infinity) of S(-) mepivacaine was almost double that of R(+)-mepivacaine. The elimination half-life (T1/2) was identical for both isomers (3 h), which means that the calculated total body clearance and the calculated steady-state volume of the distribution of R(+) are, respectively, 1.7 and 1.5 times larger than that of the S(-) isomer. We conclude that the plasma concentrations of the S(-)-mepivacaine isomer were higher than those of the R(+) isomer because of a smaller volume of distribution and a slower total body clearance. PMID- 1616167 TI - Antinociceptive effects of phenobarbital in "tail-flick" test and deafferentation pain. AB - Deafferentation pain has been related to abnormal electrical hyperactivity in the neurons of the sensory relays in the central nervous system. This electrical activity resembles the epileptoid pattern observed in experimental epileptoid foci. With the aim of preventing this hyperactivity, rats were given long-term treatment with phenobarbital after sciatic transection and dorsal cervical rhizotomy. Daily intramuscular injections of saline solution or 5 and 10 mg/kg of phenobarbital were administered for 20 days, starting 10 days before surgery. Larger doses of phenobarbital delayed the onset and reduced the severity of autotomy. In a test of acute pain, the effect of intraperitoneal (1-16 mg) and intrathecal (100-500 micrograms) phenobarbital was studied by measuring the "tail flick" response latency. Intraperitoneal phenobarbital did not modify acute pain, but 500 micrograms of intrathecal phenobarbital increased the threshold of pain. These results indicate that (a) phenobarbital, a drug with anticonvulsant activity, reduces deafferentation behavior in rats, and (b) intrathecal phenobarbital has an antinociceptive action in acute experimental pain. PMID- 1616168 TI - Effects of single-dose intravenous omeprazole and ranitidine on gastric pH during general anesthesia. AB - We conducted a comparative trial of the gastric proton pump inhibitor omeprazole and the H2-receptor antagonist ranitidine on gastric pH in 50 adult patients scheduled for elective gynecologic surgery. The drugs were administered intravenously in random fashion after induction of general anesthesia and placement of a gastric electrode for continuous pH monitoring. The two drugs caused significant increases in gastric pH that did not differ significantly when compared with one another, yet there were significant differences from the control group, which did not receive either of the two drugs. A gastric pH of 2.5 was reached within median 34 and 26 min after administration of omeprazole (40 and 80 mg, respectively) and within median 32 and 26 min after administration of ranitidine (50 and 100 mg, respectively). After injection of omeprazole, a gastric pH of 3.5 was reached after median 41 and 34 min; injection of ranitidine (50 and 100 mg) produced a pH of 3.5 after median 43 and 48 min, respectively. We conclude that the intravenous administration of a single dose of omeprazole or ranitidine causes a similar increase, both in magnitude and time of onset, in gastric pH during general anesthesia. PMID- 1616169 TI - Ketorolac does not decrease the MAC of halothane or depress ventilation in rats. AB - To determine the effects of intravenous (IV) ketorolac on anesthesia and the mechanisms involved, we evaluated its effects on minimum alveolar anesthetic concentration (MAC) and ventilation in halothane-anesthetized rats. Ketorolac in clinical (0.2 and 2 mg/kg) and large (20 and 40 mg/kg) IV doses did not affect the MAC of halothane (0.82% +/- 0.02%). Resting end-tidal CO2 tension (5.1% +/- 0.1%) and the slope of the CO2 response curves (70 +/- 6 mL.min-1.%-1) were also unaffected by IV ketorolac. The mean arterial blood pressure did not significantly change after ketorolac in doses of 0.2, 2, or 20 mg/kg but decreased significantly (P less than 0.05) after 40 mg/kg (placebo 99 +/- 8 mm Hg; ketorolac 87 +/- 6 mm Hg). This study demonstrates that MAC, ventilation, and mean arterial blood pressure are unaffected by clinical doses of IV ketorolac. Furthermore, the lack of effect on MAC and ventilation from larger doses suggests that ketorolac does not have mechanisms of action in the central nervous system. PMID- 1616170 TI - Psychological science around the world. PMID- 1616171 TI - Ethnic differences in adolescent achievement. An ecological perspective. AB - Using data collected from a large sample of high school students, the authors challenge three widely held explanations for the superior school performance of Asian-American adolescents, and the inferior performance of African- and Hispanic American adolescents: group differences in (a) parenting practices, (b) familial values about education, and (c) youngsters' beliefs about the occupational rewards of academic success. They found that White youngsters benefit from the combination of authoritative parenting and peer support for achievement, whereas Hispanic youngsters suffer from a combination of parental authoritarianism and low peer support. Among Asian-American students, peer support for academic excellence offsets the negative consequences of authoritarian parenting. Among African-American youngsters, the absence of peer support for achievement undermines the positive influence of authoritative parenting. PMID- 1616172 TI - The mental health system and older adults in the 1990s. AB - Trends in mental health services for older adults during the past decade were used to predict salient issues for the current decade. These include overreliance on inpatient treatment, increased use of general hospitals as treatment sites, inadequate integration with the nursing-home industry, and insufficient mental health referrals from general medical providers. In the decade ahead, the mental health needs of older adults are unlikely to be an identified focus; rather the issues will overlap with other priorities (e.g., biomedical research on brain functioning, alternative treatment programs for the chronically mentally ill, and containing health care costs). Advocates for the elderly will be successful to the extent that they cast aging services within the context of these other concerns. PMID- 1616173 TI - Is the unconscious smart or dumb? AB - How sophisticated is unconscious cognition? This is one of the most fundamental questions about the unconscious that has been posed by research psychologists over the past century. Anthony Greenwald takes a contemporary look at this classical problem and concludes that unconscious cognition is severely limited in its analytic capability. In response, other leading scholars agree that the reality of unconscious processes is no longer questionable. Although there is some disagreement about just how sophisticated these processes are, the consensus is that exciting times are ahead for both research and theory concerning the mental processes involved in unconscious cognition. PMID- 1616174 TI - New look 3. Unconscious cognition reclaimed. AB - Recent research has established several empirical results that are widely agreed to merit description in terms of unconscious cognition. These findings come from experiments that use indirect tests for immediate or long-term residues of barely perceptible-but-unattended, or attended-but-forgotten events. Importantly, these well-established phenomena--insofar as they occur without initially involving focal attention--are limited to relatively minor cognitive feats. Unconscious cognition is now solidly established in empirical research, but it appears to be intellectually much simpler than the sophisticated agency portrayed in psychoanalytic theory. The strengthened position of unconscious cognitive phenomena can be related to their fit with the developing neural network (connectionist) theoretical framework in psychology. PMID- 1616175 TI - Another look at New Look I. PMID- 1616176 TI - Psychodynamics and the unconscious. PMID- 1616177 TI - The psychological unconscious. Found, lost, and regained. AB - In response to Greenwald's article on contemporary research on unconscious mental processes, the authors address three issues: (a) the independence of much recent research and theory from psychodynamic formulations; (b) the broad sweep of the psychological unconscious, including implicit perception, memory, thought, learning, and emotion; and (c) the possibility that the analytic power of unconscious processing may depend both on the manner in which mental contents are rendered unconscious and the manner in which they are to be processed. PMID- 1616178 TI - Perception without awareness. Critical issues. PMID- 1616179 TI - Nonconscious acquisition of information. AB - The authors review and summarize evidence for the process of acquisition of information outside of conscious awareness (covariations, nonconscious indirect and interactive inferences, self-perpetuation of procedural knowledge). Data indicate that as compared with consciously controlled cognition, the nonconscious information-acquisition processes are not only much faster but are also structurally more sophisticated, in that they are capable of efficient processing of multidimensional and interactive relations between variables. Those mechanisms of nonconscious acquisition of information provide a major channel for the development of procedural knowledge that is indispensable for such important aspects of cognitive functioning as encoding and interpretation of stimuli and the triggering of emotional reactions. PMID- 1616180 TI - Unconscious influences revealed. Attention, awareness, and control. AB - Recent findings of dissociations between direct and indirect tests of memory and perception have renewed enthusiasm for the study of unconscious processing. The authors argue that such findings are heir to the same problems of interpretation as are earlier evidence of unconscious influences--namely, one cannot eliminate the possibility that conscious processes contaminated the measure of unconscious processes. To solve this problem, the authors define unconscious influences in terms of lack of conscious control and then describe a process dissociation procedure that yields separate quantitative estimates of the concurrent contributions of unconscious and consciously controlled processing to task performance. This technique allows one to go beyond demonstrating the existence of unconscious processes to examine factors that determine their magnitude. PMID- 1616181 TI - Postsplenectomy leukocystosis: physiologic or an indicator of infection? AB - The records of 42 patients who underwent splenectomy following blunt abdominal trauma were reviewed to determine whether white blood cell (WBC) count is a useful indicator of acute infection in the postoperative period. Patients, ranging in age from 14 to 54 years, were divided into two groups: 1) infected (n = 18) and 2) noninfected (n = 24). Group average daily WBC counts (thousands/mm3) and differential counts (polymorphonuclear leukocyte/bands) were evaluated for the first 14 postoperative days. The infected group had a mean WBC of 21.2 and a mean differential count of 73/8. The average daily WBC count began to rise on Day 4 (WBC = 10.8) and peaked on Day 7 at 27.8. There were 30 episodes of infection: 14 pneumonias and 16 others, including sinusitis, empyema, subphrenic abscess, urinary tract infection, and bacteremias. The noninfected group had a mean WBC count of 14.2 and a mean differential of 73/5. For this group, the average WBC peaked by the postoperative Day 2 (WBC = 15.9), then the trend was downward. Thus, for patients with traumatic splenic injuries, WBC count may predict infection in the postsplenectomy period. In the noninfected group, the authors observed no average daily WBC count above 16; whereas, in the infected group, no average daily WBC count less than 16 was observed. The differential counts were not significantly different between the two groups. PMID- 1616182 TI - Portable ultrasonography in critical care. AB - A 2-year retrospective analysis of portable ultrasound examinations in the intensive care unit was conducted to evaluate the indications and efficacy of portable sonography. A total of 86 examinations were performed on 79 patients. Of these, 22 per cent of the examinations supported the suspected diagnosis and contributed to treatment. Seventy per cent of the examinations excluded the suspected diagnosis. There was a 9 per cent incidence that yielded unsuspected information that contributed to treatment. Only 8 per cent of the examinations were misleading or proven false. The authors found that with an overall sensitivity of 79 per cent and specificity of 97 per cent, portable ultrasonography is a valuable, relatively inexpensive test in the critical care setting. PMID- 1616183 TI - Hepatic enzyme response and hyperpyrexia after severe liver injury. AB - A multi-center experience with 210 severe liver injuries was reviewed to define postoperative changes in hepatic enzyme levels and body temperature profile. The 129 patients who survived initial operation comprised the data base. Serum glutamic oxaloacetic transaminase (SGOT) and lactate dehydrogenase (LDH) peaked within 24 hours (750 +/- 92 IU/L, 870 +/- 120 IU/L) and decreased rapidly during the first 4 days. Serum bilirubin was maximal at 7 days, while alkaline phosphatase rose slowly throughout 14 days. Hepatic enzyme elevations were more dramatic after blunt trauma, reflecting greater hepatocellular disruption. Maximum daily temperatures exceeding 38.0 degrees C and 39.0 degrees C were recorded for the first 3 postoperative days in 82 (64%) patients and 14 (11%) patients, respectively. No infectious source was evident in 13 (93%) of 14 patients with severe hyperpyrexia, implicating release of inflammatory mediators associated with major hepatic trauma. Convalescence from severe hepatic injury is marked by release of SGOT and LDH, as well as fever, which may be anticipated during the first 4 days postinjury. PMID- 1616184 TI - Giant, benign, mucinous cystadenoma of the ovary: case study and literature review. AB - Benign, mucinous cystadenomas account for 15 per cent of all ovarian neoplasms. Of these, the giant variant occurs rarely. A morbidly obese, 52-year-old, white woman was seen for acute abdominal pain and diagnosed using computerized tomography as having a giant, benign, mucinous cystadenoma. At laparotomy, 21-kg cystic mass attached to the right ovary was removed. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. In such patients, special consideration must be given to hemodynamic and ventilatory monitoring and intraoperative fluid management. Recognition and subsequent surgical management of this and other large abdominal masses can be optimized by thoughtful, preoperative evaluation and careful planning of the operative approach. PMID- 1616185 TI - Transareolar dye-injection microdochectomy. AB - Single-duct microdochectomy is described for use in patients with bloody or serosanguinous nipple discharge arising from a single duct in the breast. Because most such cases are caused by benign, intraductal papillomata, the technique used in removing the offending ductal system should be fully diagnostic, adequately therapeutic, and cosmetically acceptable. A technique is described that is used in 40 consecutive patients with good diagnostic, therapeutic, and cosmetic result. The procedure itself combines techniques and principles of plastic and reconstructive surgery such as minimal tissue trauma, use of anatomical tissue planes, bloodless-field surgery, and microdissection. PMID- 1616186 TI - The significance of breast complaints as correlated with age and breast cancer. AB - A review is presented of 2,000 consecutive new, patients with breast complaints. Emphasis is placed on the specific complaint as correlated with patient age and the incidence of breast cancer. The initial complaints were a lump (50%), an abnormal mammogram (32%), other complaints (8%), breast pain (6%), and nipple discharge (4%). Follow-up information was available for 1,889 patients. The majority of the patients (68%) were under 50 years of age. Of 831 patients to whom a biopsy was recommended, 720 ultimately had a biopsy and 147 cancers were identified. Sixty-five per cent of the cancers were in women aged 50 years or greater. Of the patients aged 50 years or older, 16.1 per cent had breast cancer, while only 4.0 per cent of the patients less than 50 years and 0.8 per cent of the patients less than 30 years of age had breast cancer. The author concludes that the overwhelming majority of patients (92%) referred to a breast surgery practice do not have malignancy. Thus, primary physicians undoubtedly see even a smaller per cent of breast complaints ultimately result in the diagnosis of breast cancer. There is a need to better inform the public as to the significance of breast complaints and to establish more specific criteria for biopsy, particularly in the young, professional, liability threats not withstanding. PMID- 1616187 TI - Primary malignant melanoma of the small bowel: a case study. AB - Malignant melanoma involving the gastrointestinal (GI) tract is diagnosed premortem in only 4 per cent of patients with the disease, even though in autopsy series 60 per cent of patients who died of malignant melanoma have GI metastases. Usually, these GI lesions are metastatic. However, a few cases of primary GI malignant melanoma have been reported. Such a case is reported and discussed, including the clinical presentation, pathophysiology, treatment, and prognosis of this disease. PMID- 1616188 TI - Preoperative irradiation and surgery for initially unresectable adenocarcinoma of the rectum. AB - Forty-two patients with initially unresectable rectal adenocarcinoma were treated with preoperative irradiation and surgery between March 1970 and March 1986 at the University of Florida (Gainesville, FL). No patient received adjuvant chemotherapy. All patients had follow-up for at least 5 years; 23 (55%) had follow-up for 10 years or more. Five patients (12%) underwent an exploratory laparotomy before irradiation; the remaining 37 patients were clinically thought to have unresectable disease. Eighteen patients had tumor fixation to one structure, and 24 patients (57%) had fixation to two or more structures. Lesions that exhibited impaired mobility but not complete fixation were considered to be clinically resectable and are not included in this series. The dose of preoperative irradiation ranged from 3,500 to 6,000 cGy at 180 cGy per fraction; 30 of 42 patients received 4,500 to 5,000 cGy and only 4 patients received less than 4,000 cGy. Forty-one patients were operated on 1 to 11 (mean 4.6) weeks after the completion of radiotherapy; 1 patient died of aspiration pneumonia after completing irradiation but before the planned resection. Resection of the rectal cancer was accomplished in 37 patients. Four patients were found to have extensive unresectable disease at laparotomy. Twenty-one patients had a complete resection: 11 were stage B2, and 10 were stage C2. Twenty patients had incomplete resection due to positive margins (8 patients), distant metastases with or without positive margins (8 patients), or no resection due to extensive disease (4 patients). Two patients died after the operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616189 TI - Selective nonoperative management of solid breast masses. AB - A prospective study evaluated the hypothesis that, following consistent clinical and mammographic guidelines, many women with breast masses can be nonoperatively managed. One hundred eighty women with solid breast masses were assigned both a clinical and mammographic diagnosis by each a surgeon and radiologist. Immediate biopsy (n = 78) was recommended when either clinician thought that the mass was malignant (52 cancers). The remainder were offered a trial of observation, with interval biopsy performed upon patient preference or for increased clinical/mammographic concern. Of the 89 who consented to this, 70 received long term follow-up (X = 22 months) with improvement in the characteristics of the mass. The diagnosis of invasive cancer was delayed in two women initially observed, with no apparent impact on survival. It is concluded that many women with solid breast masses can be safely observed. Biopsy remains warranted for any mass suspicious for malignancy on clinical/mammographic grounds, or if follow-up cannot be assured. PMID- 1616190 TI - [Chronic rhinitis]. PMID- 1616191 TI - [Alcohol consumption in children: polling the parents]. AB - Alcoholism is a major health problem in Spain. Frequently, the first drink is offered in the home. We report the results of a poll in which parents were asked when they offer alcohol to their children. We found that 76.1% offered alcohol anytime. Furthermore, 15% of the mothers answered that this may be of benefit to their children. Drinks with a higher level of alcohol (brandy, punch, anis) were offered more frequently after seven years of age and to those children whose mother had offered the first alcoholic beverage at an earlier age. PMID- 1616192 TI - [Redistribution of fetal cardiac output in intrauterine growth retardation]. AB - One hundred and thirty-one fetuses with a gestational age between 29 and 41 weeks have been studied by Doppler-Echocardiography. The cases include normal pregnancies and those with a risk for congenital heart disease. We compared the cardiac output distribution, calculated by Pulsed Doppler-Echocardiography, between the intrauterine growth retardation cases and those with normal growth. The normal and relative dominance of the right versus the left ventricle is demonstrated in normal pregnancies and normal growth fetuses. This ratio is clearly inverted in the growth-retarded cases. This redistribution of blood flow may be a response to chronic hypoxia allowing preferential flow of the blood to the brain. PMID- 1616193 TI - [Dermoid cyst of the anterior fontanelle in children: clinical significance and differentiation from encephalocele]. AB - Dermoid cysts of the anterior fontanel present as a tumor lesion that tenses up when the child cries or strains. Their midline position in the skull, the fact that some of these cysts contain clear fluid and the presence of an underlying bone defect, lead the clinician to the erroneous diagnosis of encephalocele, for which they are sent for consultation. We report a series of five of these cysts (3 dermoid and 2 epidermoid) located over the anterior fontanel, remark on their clinical significance, and stress their differential diagnosis from encephalocele and from other tumor lesions of the anterior fontanel. PMID- 1616194 TI - [Comparison of treatment of acute asthma attacks in children with salbutamol dispensed by the Volumatic dispenser or by a nebulizer]. AB - Eighteen children with acute asthma were administered equal doses of Salbutamol either through a nebulizer and face mask or a dose-metered inhaler, spacer (Volumatic) and tidal breathing mechanism. Consecutive doses at twenty minute intervals were administered until either no significant improvement in pulmonary function was observed or until a cumulative dose of 0.15 mg/Kg (maximum of 5 mgs) had been given. All subjects finally received a dose of 0.15 mg/Kg (maximum of 5 mgs) of nebulized Salbutamol at the end of the study. No difference in bronchodilation was obvious between the methods of treatment. No significant side effect was observed in any patient. Treatment of acute asthma in children with Salbutamol via a pressurized inhaler, spacer and tidal breathing mechanism may be an efficacious, safe and readily available method, but further work is needed before it can be recommended for routine home management of asthma attacks. PMID- 1616195 TI - [Pulmonary mechanism in preterm neonates without respiratory problems]. AB - Pulmonary function was measured by computerized pneumotacography in 26 preterm newborn infants without respiratory problems. Mean (+/- SD) for birth weight, gestation and postnatal age were 2,034 +/- 412 g, 34.1 +/- 1.7 weeks, and 2.2 +/- 1.6 days, respectively. An esophageal balloon, a differential transducer and nasal prongs were used to measure pressure and flow. The following parameters were measured in each respiration by the mean squares method: Dynamic compliance (Cdyn), total respiratory resistance (RRt) and work (WRt), respiratory time constant (KTt), rate (f) and maximal inspiratory and expiratory flows (PIF, PEF). Replication of the method was found to be good, as the differences between two determinations were not significant (p less than 0.05). The mean differences were less than 6.26%. The mean (+/- SD) and the 3rd and 97th percentiles for each parameter were the following: f: 52 +/- 7 (39-66) r.p.m., Tv: 6.6 +/- 1.1 (4.5 8.7) ml/kg, Vmin: 342 +/- 82 (128-502) ml/min, Cdin: 3.7 +/- 1.1 (1.5-6) ml/cm, RRt: 83 +/- 47 (37-204) cm/L/sec, TRt: 27 +/- 15 (2-57.1) g/cm/kg, PIF: 2.2 +/- 0.5 (1.1-3.2) L/min and PEF: 1.9 +/- 0.6 (0.7-3) L/min. PMID- 1616196 TI - [Importance of maternity routines in the success of maternal breast feeding]. AB - Many of the problems that are associated with breast-feeding appear to be caused by various postnatal care procedures that take place in the majority of our hospitals. In order to identify these obstacles, a survey was carried out on a sample of 400 mothers whose children were born in Mostoles in 1989. The results were as follows: 1) The average duration of breast-feeding was 2.43 months (SD = 2.19 months). 2) The lower the baby's birth weight and the longer that he was kept in the hospital, the shorter the time that he was breast-fed. Two basic procedures in the hospital "norms" appear to contribute to the failure of breast feeding. First, the provision of glucose water or formula bottles and second, a ridged feeding schedule. If the newborn was fed on demand in the hospital it tended to be continued once at home. In both the hospital and in the home, on demand feeding was strongly associate with successful breast-feeding. Some simple modifications to the Maternity departments are recommended. PMID- 1616197 TI - [Phenylalanine metabolites in hyperphenylalaninemic children]. AB - Phenylalanine and its organic acid derivatives, phenylacetate, mandelic, o hydroxy-phenylacetate, phenyllactate and phenylpyruvate are increased due to the enzymatic block in the normal pathway of phenylalanine metabolism in phenylketonuric and hyperphenylalaninemic patients. These organic acids are neurotoxic and whether they are responsible for behavior and learning problems in hyperphenylalaninemic children remains to be seen. The purpose of the present study was to evaluate: 1) variations of the organic acid derivatives of phenylalanine during dietary treatment and 2) the usefulness of its determination to further adjust the phenylketonuric diet. Twenty-eight children, ages 4 months to 16 years, were studied. On the same day, the level of phenylalanine in the plasma and phenylalanine metabolites in freshly collected urine samples were tested. Phenylalanine metabolites were detected in some patients with blood phenylalanine levels below 242 microM/L and they rose as levels of blood phenylalanine increased with the phenylpyruvic acid being the highest when blood phenylalanine levels were greater than 424 microM/L. These compounds are usually not detected in normal urine. However, we have or learning problems, thus we do not make further adjustments in the PKU diet on the basis of phenylalanine metabolites. PMID- 1616198 TI - [Treatment of preterm neonates with severe respiratory distress syndrome using exogenous natural surfactants of porcine origin]. AB - From September 1989 to September 1990, a total of 25 newborn infants with severe RDS (on mechanical ventilation and with a FiO2 above 0.6) were treated with porcine surfactant (Curosurf), since its efficacy has been demonstrated in a prior clinical trial (Pediatrics 1988; 82: 683-91). The mean birth weight and gestational age were 1,327 +/- 566 g and 29.5 +/- 3.8 weeks, respectively. Twenty four percent of the babies had an arterial pH below 7.1. At a mean postnatal age of 9.1 +/- 10.7 hours, a dose of 200 mg/Kg of Curosurf was given by the tracheal route. Mean paO2 rose from 47 +/- 14 mm Hg to 166 +/- 64 mm Hg (p less than 0.001). The paO2 increased in 24 of the 25 cases and in 20 (80%) the post treatment paO2 was a least two times higher than the pre-treatment value. An hour after surfactant treatment, the paCO2 decreased from 58 +/- 21 mm Hg to 45 +/- 16 mm Hg (p less than 0.01) and the pH increased from 7.19 +/- 0.15 to 7.28 less than 0.11 (p less than 0.001). The following complications were observed: pulmonary interstitial emphysema (16%), pneumothorax (8%), patent ductus arteriosus (36%), intraventricular hemorrhage (28%) and bronchopulmonary dysplasia (24%). The neonatal survival rate and the survival rate after discharge from the hospital were 76% and 64%, respectively. The combined survival and absence of DBP was 32%. Nonsurvivors had lower birth weights and gestation ages, as well as lower paO2 5 min after treatment and higher FiO2 24 hours after surfactant treatment than did the survivors. PMID- 1616199 TI - [Factors influencing election and duration of maternal breast feeding]. PMID- 1616200 TI - [Mortality caused by accidental suffocation during the first year of life]. AB - We have analyzed the mortality due to accidental choking and suffocation during the first year of life that occurred in Spain from 1970 to 1980. The annual mortality rate due to choking caused by foodstuffs increased considerably from 1970 (5.7 deaths per 100,000) to 1977 (34.47 deaths per 100,000) and then declined slightly. Overall, mortality from this cause increased by a factory of five throughout the decade. This surprising evolution and its causes at a time when infant mortality is declining are discussed. PMID- 1616201 TI - Pseudosubluxation of C2-C3 in childhood: a frequent clinico-radiological diagnostic error. AB - Although serious cervical injuries in pediatric patients are very infrequent, the may occur occasionally as a result of a strong blow to the head. Clinical records and radiological pictures, and in some cases computer tomography, help to provide the correct diagnosis. During childhood there are several normal radiological variants that may be interpreted as pathological findings, of which pseudosubluxation C2-C3 is the most frequent. We present two such cases and discuss the clinical and radiological criteria for the differential diagnosis between normal variants and injuries to the cervical spine in pediatric patients. PMID- 1616202 TI - [Recurrent infections in glycogenosis type Ib]. PMID- 1616203 TI - [Neonatal sepsis and meningitis caused by Haemophilus influenzae]. PMID- 1616204 TI - [Atypical measles with hepatic involvement]. PMID- 1616205 TI - [Prenatal diagnosis of neuroblastoma]. PMID- 1616206 TI - [Administration of immunotherapy with allergens: importance of measuring the maximal expiratory flow rate]. PMID- 1616207 TI - [And they still want more?]. PMID- 1616208 TI - [Pancreatic heterotopy as a cause of intestinal invagination]. PMID- 1616209 TI - [Pediatric emergencies]. PMID- 1616210 TI - [Recurrent condyloma acuminatum in an infant]. PMID- 1616211 TI - An outbreak of tuberculosis caused by multiple-drug-resistant tubercle bacilli among patients with HIV infection. AB - OBJECTIVE: To evaluate a nosocomial outbreak of tuberculosis caused by multiple drug-resistant bacilli among patients with tuberculosis and HIV infection. DESIGN: A case-control study. PATIENTS: Patients with HIV infection and culture proven tuberculosis. MEASUREMENTS: Patient characteristics, date of diagnoses of HIV infection and disease, date of diagnosis of tuberculosis, Mycobacterium tuberculosis susceptibility results, and medical center contact. RESULTS: Sixty two patients who had tuberculosis caused by multiple-drug-resistant bacilli (cases) and 55 patients who had tuberculosis caused by susceptible or single-drug resistant bacilli (controls) were identified. Controls were more likely to be black (odds ratio, 0.4; 95% CI, 0.2 to 0.9) or Haitian (odds ratio, 0.2; CI, 0.1 to 0.6) compared with cases, who were more likely to be homosexual men (odds ratio, 2.9; CI, 1.3 to 6.4). Forty-four cases (71%) had previous contact with an HIV clinic compared with 15 controls (27%) (P less than 0.0001). Cases were more likely to have had AIDS (odds ratio, 7.7; CI, 1.5 to 53.7), to have been hospitalized on an HIV ward (odds ratio, 8.3; CI, 2.3 to 29.7), to have been seen in an HIV clinic (odds ratio, 7.8; CI, 3.4 to 18.1), to have received intravenous therapy in an HIV clinic (odds ratio, 13.0; CI, 4.6 to 37.0), or to have received inhalation pentamidine in an HIV clinic before a diagnosis of tuberculosis was made. Multiple logistic regression analysis showed that a diagnosis of AIDS (odds ratio, 11.2; CI, 3.1 to 40.6) and HIV clinic visits (odds ratio, 13.0; CI, 2.7 to 63.7) before a diagnosis of tuberculosis were significantly associated with tuberculosis caused by multiple-drug-resistant bacilli. Using susceptibility patterns and appointment dates, we found that 22 cases had previous contact with a person who had tuberculosis caused by multiple-drug-resistant bacilli in the HIV clinic. CONCLUSIONS: Nosocomial transmission of M. tuberculosis from other HIV-infected patients with tuberculosis caused by multiple-drug-resistant bacilli can occur. These findings have serious public health implications and demand strict adherence to acid-fast bacilli isolation precautions. PMID- 1616212 TI - Clinical presentation and outcome of patients with HIV infection and tuberculosis caused by multiple-drug-resistant bacilli. AB - OBJECTIVE: To determine the clinical manifestations of patients with human immunodeficiency virus (HIV) infection and tuberculosis caused by multiple-drug resistant bacilli compared with those with single-drug-resistant or susceptible bacilli. DESIGN: Descriptive, case-control, and cohort studies. SETTING: A large urban teaching hospital. PATIENTS: Sixty-two patients with tuberculosis caused by multiple-drug-resistant bacilli (cases) and 55 patients with tuberculosis caused by single-drug-resistant or susceptible bacilli (controls). MEASUREMENTS: Characteristics of clinical presentation, radiographs, pathologic abnormalities, antituberculosis treatment, and clinical course. RESULTS: Twenty cases (32%) had concomitant pulmonary and extrapulmonary disease at presentation compared with 9 controls (16%; odds ratio, 2.4; 95% CI, 1.0 to 5.9). More cases had alveolar infiltrates (76%; odds ratio, 3.6; CI, 1.2 to 11.4), interstitial infiltrates with a reticular pattern (67%; odds ratio, 7.8; CI, 1.0 to 83.5), and cavitations (18%; odds ratio, 6.6; CI, 0.8 to 315.3) on initial chest radiographs compared with controls (49%, 19%, and 3%, respectively). Pathologic specimens from cases showed extensive necrosis, poor granuloma formation, marked inflammatory changes with a predominance of neutrophils, and abundant acid-fast bacilli. Twenty-five cases received two or more effective antituberculosis drugs for more than 2 months. Only 2 cases had three consecutive negative cultures for Mycobacterium tuberculosis; one patient died within 1 day of the last negative culture, and the other had positive cultures 496 days later. The remaining 23 cases had persistently or intermittently positive cultures despite therapy. The clinical course of these cases suggested overwhelming miliary tuberculosis with involvement of the lungs (77%), pleura (15%), stool (34%), meninges (13%), bone marrow (16%), blood (10%), lymph nodes (10%), and skin (8%). The median survival time was 2.1 months for cases compared with 14.6 months for controls (P = 0.001, log-rank test). CONCLUSIONS: Tuberculosis caused by multiple-drug-resistant bacilli in patients with HIV infection is associated with widely disseminated disease, poor treatment response with an inability to eradicate the organism, and substantial mortality. PMID- 1616213 TI - Rapid suppression of spontaneous ventricular arrhythmias during oral amiodarone loading. AB - OBJECTIVE: To determine the time course of effects of amiodarone during an oral loading period. DESIGN: A prospective, nonrandomized study. SETTING: Arrhythmia referral center at a university hospital. PATIENTS: Fifty patients with refractory sustained ventricular tachycardia (n = 44) or ventricular fibrillation (n = 6) and frequent (greater than or equal to 30/h) ventricular premature complexes. INTERVENTION: Oral amiodarone, 1200 mg/d for 14 days and 400 mg/d thereafter. MEASUREMENTS: Ambulatory electrocardiographic monitorings, 12-lead electrocardiograms, and amiodarone blood levels on days 3, 5, 7, 9, 11, 13, and 28. RESULTS: Dramatic reductions of ventricular arrhythmias were noted during the first 72 hours of the therapy. Average ventricular premature complexes/h, couplets/h, and nonsustained ventricular tachycardias/24 h were 524 +/- 1224/h, 16 +/- 61/h, and 167 +/- 611/24 h, respectively, at baseline, and reduced to 140 +/- 243/h, 11 +/- 50/h, and 33 +/- 117/24 h, respectively, on day 3 (P less than 0.05 for all). Subsequent reductions of ventricular arrhythmias from day 3 to day 13 were more gradual but were still significant (P less than 0.05). A significant reduction of ventricular arrhythmias (greater than or equal to 70% reduction of ventricular premature complexes and greater than or equal to 90% reduction of nonsustained ventricular tachycardias) was noted in 50% of patients on day 3, in 65% on day 7, and in 83% on day 13. Prolongation of the QT interval exhibited a similar time course. There were no further differences in reduction of ventricular premature complexes or QT intervals between day 13 and day 28. CONCLUSIONS: Oral amiodarone given in loading doses produces rapid and dramatic reductions in spontaneous ventricular arrhythmias within 72 hours. Subsequent reductions of spontaneous arrhythmia were gradual and less dramatic. PMID- 1616214 TI - Empiric treatment of acute diarrheal disease with norfloxacin. A randomized, placebo-controlled study. Swedish Study Group. AB - OBJECTIVE: To evaluate the clinical and microbiologic efficacy and safety of norfloxacin for acute diarrhea. DESIGN: Double-blind, placebo-controlled, randomized clinical multicenter trial. SETTING: Six departments of infectious disease. PARTICIPANTS: Patients 12 years of age or older with a history of acute diarrhea lasting 5 or fewer days. Eighty-five percent of patients (511/598) were evaluable for efficacy. Of these evaluable patients, 70% had traveled abroad within the previous 6 weeks. INTERVENTIONS: Patients received either norfloxacin, 400 mg, or placebo twice daily for 5 days. MEASUREMENTS: Enteric pathogens were isolated in 51% of the evaluable patients: Campylobacter species in 29%, Salmonella species in 16%, Shigella species in 3.5%, and other pathogens in 2.6%. RESULTS: Norfloxacin had a favorable overall effect compared with placebo (cure rate, 63% compared with 51%; P = 0.003). There were statistically favorable effects in culture-positive patients, patients with salmonellosis, and severely ill patients but not in culture-negative patients or patients with campylobacteriosis or shigellosis. A significant difference was noted between norfloxacin and placebo in median time to cure among all evaluable patients (3 compared with 4 days, P = 0.02) and in patients with campylobacteriosis (3 compared with 5 days, P = 0.05) but not in patients. Culture-positive, but not culture-negative patients, in the norfloxacin group had significantly fewer loose stools per day compared with patients in the placebo group from day 2 onward (P less than or equal to 0.01). Norfloxacin was significantly less effective than placebo in eliminating Salmonella species on days 12 to 17 (18% compared with 49%, P = 0.006), whereas the opposite was true for Campylobacter species (70% compared with 50%, P = 0.03). In six of nine patients tested, norfloxacin resistant Campylobacter species (MIC, greater than or equal to 32 micrograms/mL) appeared after norfloxacin treatment. CONCLUSION: Empiric treatment reduced the intensity and, to some extent, the duration of symptoms of acute diarrhea. The effect was restricted to patients who had bacterial enteropathogens or who were severely ill. The clinical usefulness of this treatment is limited by the fact that norfloxacin seems to delay the elimination of salmonella and to induce resistance in campylobacter. PMID- 1616215 TI - The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis of ascites. AB - OBJECTIVE: To compare the serum-ascites albumin gradient to the exudate transudate concept in the classification of ascites. DESIGN: Prospective collection of ascitic fluid data from patients with well-characterized causes of ascites. SETTING: Hepatology inpatient and outpatient ward and consult service of a large, urban hospital. PATIENTS: A total of 901 paired serum and ascitic fluid samples were collected from consecutive patients with all forms of ascites. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The utility of the serum-ascites albumin gradient and the old exudate-transudate concept (as defined by ascitic fluid total protein concentration [AFTP]) were compared for their ability in discriminating the cause for ascites formation. RESULTS: The albumin gradient correctly differentiated causes of ascites due to portal hypertension from those that were not due to portal hypertension 96.7% of the time. The AFTP, when used as defined in the old exudate-transudate concept, classified the causes of ascites correctly only 55.6% of the time. This resulted in part because the AFTP of most spontaneously infected samples (traditionally expected to be exudates) was low, and the AFTP of most cardiac ascites samples (traditionally expected to be transudates) was high. CONCLUSIONS: The exudate-transudate concept should be discarded in the classification of ascites. The serum-ascites albumin gradient is far more useful than the AFTP as a marker for portal hypertension, but the latter remains a useful adjunct in the differential diagnosis of ascites. PMID- 1616216 TI - Fabry disease: an unusual cause of severe coronary disease in a young man. PMID- 1616217 TI - The treatment of diabetic retinopathy: a view for the internist. AB - PURPOSE: To review the status of surgical and medical therapy for diabetic retinopathy from the perspective of the non-ophthalmologist. DATA SOURCES: Relevant English-language articles published from January 1981 to July 1991 were identified through MEDLINE. Other relevant articles were obtained from the authors' personal database. STUDY SELECTION: For the review of surgical treatment, large randomized, controlled trials were selected. For the review of medical treatment, randomized studies comparing intensive insulin treatment with conventional insulin therapy were selected, as were double-blind, randomized, controlled trials of aldose-reductase inhibitor therapy and antiplatelet therapy in patients with diabetic retinopathy. DATA EXTRACTION: Emphasis is on findings from large, multicenter, randomized, controlled studies. DATA SYNTHESIS: Surgery is effective in three clinical situations: Panretinal (scatter) photocoagulation is effective treatment for proliferative retinopathy that is likely to progress to severe visual loss, with such therapy resulting in a 50% to 60% decrease in the main outcome (visual acuity of 5/200 or less; focal photocoagulation decreases the incidence of deterioration of visual acuity by 60% in patients with clinically significant macular edema, but no benefit of photocoagulation has been shown in patients with mild-to-moderate background diabetic retinopathy; and vitrectomy is effective in improving visual acuity only in patients with severe, complicated proliferative retinopathy. Intensive insulin therapy has not been consistently effective in short-term studies with small numbers of subjects. Results of the Diabetes Control and Complications Trial should show whether intensive insulin therapy affects the course of diabetic complications. Aldose reductase inhibitors have not shown efficacy in changing the course of diabetic retinopathy. Results of trials using antiplatelet agents are controversial. CONCLUSIONS: Current therapy of diabetic retinopathy is based on detection and surgical treatment of advanced lesions. Medical interventions that effectively halt the progression or prevent the development of diabetic retinopathy are needed. PMID- 1616218 TI - Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy. A review of the literature and pathophysiology. AB - OBJECTIVE: To review available information on cough and angioneurotic edema associated with angiotensin-converting enzyme (ACE) inhibitors. DATA SOURCES: All relevant articles from 1966 through 1991 were identified mainly through MEDLINE search and article bibliographies. STUDY SELECTION: More than 400 articles were identified; 200 reporting incidence or possible mechanisms for the side effects or both were selected. DATA EXTRACTION AND SYNTHESIS: All pertinent information, including incidence and mechanisms of ACE inhibitor-induced cough and angioedema, was reviewed and collated. CONCLUSIONS: Cough occurs in 5% to 20% of patients treated with ACE inhibitors, recurring with reintroduction of the same or another ACE inhibitor. It is more common in women. The mechanism may involve accumulation of prostaglandins, kinins (such as bradykinin), or substance P (neurotransmitter present in respiratory tract C-fibers); both bradykinin and substance P are degraded by ACE. A 4-day trial of withdrawal of the ACE inhibitor or temporary substitution of another class of antihypertensive agent inexpensively and easily ascertains if the ACE inhibitor caused the cough. Change to another ACE inhibitor or additive therapy with nonsteroidal anti-inflammatory drugs is not recommended. Prompt recognition of ACE inhibitor-related cough can prevent unnecessary diagnostic testing and treatment. Angioedema occurs in 0.1% to 0.2% of patients receiving ACE inhibitors. The onset usually occurs within hours or, at most, 1 week after starting therapy. The mechanism may involve autoantibodies, bradykinin, or complement-system components. Treatment involves first protecting the airway, followed by epinephrine, antihistamines, and corticosteroids if needed. Therapy is then resumed with an alternate class of antihypertensive agent. PMID- 1616219 TI - National Study of Internal Medicine Manpower: XIX. Trends in internal medicine residency training programs. AB - The National Study of Internal Medicine Manpower (NaSIMM) reports on the results of its 1989-1990 census of residency programs. The results are integrated into an organizational model identifying inputs, process, outputs, and environment of medical training programs. The number of residents entering internal medicine continues to grow at a relatively rapid pace. This growth is largely accounted for by foreign citizens who are graduates of foreign medical schools (AFMGs). Residents are spending an increasing proportion of their time in ambulatory care settings, but, thus far, this ambulatory care training has occurred primarily in hospital clinics and emergency rooms. The proportion of a program's residents entering general internal medicine was found in a multiple regression analysis to be negatively associated with the number of subspecialty programs located in the training hospital, the percent of AFMG residents in the program, and the presence of a preliminary track in the program. PMID- 1616220 TI - A leap of faith. What can we do to curtail intrainstitutional transmission of tuberculosis? AB - Large-scale, epidemic transmission of tuberculosis to patients, nonprofessional staff, nurses, and physicians has been documented recently in hospitals, clinics, acquired immunodeficiency syndrome (AIDS) residencies, and correctional facilities. Prominent factors in these outbreaks have included human immunodeficiency virus (HIV) infection and AIDS, delayed diagnosis of tuberculosis, multidrug-resistant strains of tuberculosis that resulted in protracted shedding of mycobacteria, and ventilation patterns in buildings that resulted in the accumulation of infectious particles. Multiple deaths from tuberculosis have resulted. Various strategies, including vaccines, masks, augmented ventilation, air filters, and ultraviolet irradiation have been proposed to control this situation. Although no well-controlled studies exist to document the utility of any of these modalities, ultraviolet germicidal irradiation seems both the best theoretical model and the most practical tactic. Ultraviolet systems should be widely deployed throughout high-risk institutions. PMID- 1616221 TI - Disconnecting a ventilator at the request of a patient who knows he will then die: the doctor's anguish. PMID- 1616222 TI - Activism in academic internal medicine. PMID- 1616223 TI - Treating sickle cell pain like cancer pain. PMID- 1616224 TI - Subcutaneous compared with intravenous heparin for deep vein thrombosis. PMID- 1616225 TI - Subcutaneous compared with intravenous heparin for deep vein thrombosis. PMID- 1616226 TI - Subcutaneous compared with intravenous heparin for deep vein thrombosis. PMID- 1616227 TI - Subcutaneous compared with intravenous heparin for deep vein thrombosis. PMID- 1616228 TI - TIPS and variceal bleeding. PMID- 1616229 TI - Alpha-interferon-induced nodular rheumatoid arthritis in renal cell carcinoma. PMID- 1616230 TI - HIV infection in the workplace: protecting the vulnerable. PMID- 1616231 TI - Covering for impaired residents. PMID- 1616232 TI - ACP practice guidelines. PMID- 1616233 TI - Medical use of marijuana. PMID- 1616234 TI - Medical use of marijuana. PMID- 1616235 TI - [Current techniques for investigating exocrine pancreatic function in children]. AB - The exocrine pancreas produces many of the enzymes responsible for the digestion of food. Severe alterations in exocrine pancreas function cause malabsorption which predominantly affects fats. Unfortunately, because it is a deep organ the pancreas is a difficult target for investigations. A large number of diagnostic tests have been developed to gather information on pancreatic function with minimal invasiveness. Although helpful in everyday practice, each of these methods investigates only one of the multiple components of pancreatic secretory function and all are relatively insensitive, i.e., detect only severe secretion deficiencies. Furthermore, none of these tests can evaluate water and electrolyte secretion. Consequently, invasive duodenal juice studies with stimulation remain the "gold standard" for evaluating exocrine pancreas function. PMID- 1616236 TI - [Outcome of children of alcoholic mothers (study of 105 cases followed to adult age) and various prophylactic findings]. AB - Thirty years after recognition of the fetal alcohol syndrome, a study of 105 affected individuals who reached adulthood provides insight into the long-term outcome of this condition. The typical facial dysmorphism undergoes odd changes, often with a long face and a bulky nose and chin, in contrast to the appearance of affected infants. The growth failure becomes slightly less marked. The malformations, which occur in 3/4 of severe forms, increase the disability although function is sometimes better than expected. In contrast, the microcephaly becomes more pronounced. This explains the psychic disorders which are the main prognostic factor: mental retardation in the most severely affected patients or severe learning disabilities and, in every case, behavior disorders and marked instability. Similar disorders are often found in siblings with no apparent dysmorphism underlining the extent of the problem and the urgent need for prophylaxis. Some of the observations made in adults, confronted to embryologic data, lead to useful inferences with respect to prophylaxis. PMID- 1616237 TI - [Value of accelerated hyposensitization with mixed allergens in severe childhood asthma]. AB - The value (in terms of decreased numbers of attacks and of hospitalizations for attacks, decreased need for asthma medications, and improved tolerance to allergens) of rush immunotherapy to a mixture of allergens was studied in children with multiple sensitizations and severe asthma (as evaluated on the number of attacks, number of hospitalizations, and dependence on corticosteroids) already receiving optimal medical therapy. Because syndromic reactions are common, rush immunotherapy should be performed in the hospital and premedication with corticosteroids may be warranted in the most severe cases. PMID- 1616238 TI - [Dopa-sensitive muscular dystonia. Segawa's syndrome. A case report]. AB - A four-year-old girl developed difficulty in walking due to dystonia of the right then left foot, rest tremor in both hands, and rigidity. These symptoms worsened upon exertion and in the evening and were remarkably responsive to L. dopa, suggesting the diagnosis of fluctuating muscular dystonia or Segawa syndrome. PMID- 1616239 TI - [Tracheal compression by an aberrant brachiocephalic trunk: diagnosis by magnetic resonance]. AB - In a full-term infant who underwent surgery for type III esophageal atresia, attempts to remove the tracheal tube postoperatively failed. Bronchoscopy disclosed external compression of the trachea in the chest. Selection of the investigations most likely to provide the etiologic diagnosis was discussed. Because of the patient's poor general condition, MRI of the mediastinal area was performed first and showed an abnormal origin of the brachiocephalic trunk which was the cause of tracheal compression. No attempt at corrective surgery was made and the patient was successfully extubated at four months of age. PMID- 1616240 TI - [Skin manifestations revealing monocytic leukemia. A case report]. AB - A three-month-old developed a deep nodule over the elbow, then two weeks later additional nodules over the trunk with enlargement of the liver and spleen. Examination of the bone marrow established the diagnosis of monocytic leukemia. Acute monocytic leukemia is the most common leukemia in infants. Skin lesions, visible as red, brown or purple nodules ("blueberry muffin lesions") and confluent areas of purpura are common and may occur as the first manifestations of the disease. These skin lesions are not specific of leukemia and other diagnoses should be considered including histiocytosis, neuroblastoma, and skin erythropoiesis (in Torch syndrome, hemolytic disease of the newborn, hereditary spherocytosis, and twin-to-twin transfusion syndrome). PMID- 1616241 TI - [Case report of skin manifestations in infantile Mediterranean kala-azar]. AB - The case of a 19-month-old girl with visceral leishmaniasis and unusual skin manifestations is reported. Emphasis is put on the fact that such manifestations are unusual in Mediterranean infantile leishmaniasis. The clinical features, parasitology, histology, and course of these skin lesions are discussed. PMID- 1616242 TI - [Association of Hbo Arab/beta-thalassemia discovered fortuitously in 2 brothers]. AB - A four-year-old boy admitted for fever and a skin rash was diagnosed as having a rickettsial infection. Regenerative microcytic anemia and enlargement of the spleen were also found. Hemoglobin electrophoresis and a family study disclosed a combination of two heterozygous hemoglobinopathies, i.e., HbO Arab and beta thalassemia. A male sibling had the same anomalies as the index patient and was free of symptoms. PMID- 1616243 TI - [X-ray findings in pulmonary tuberculosis in children and its complications]. AB - Pulmonary tuberculosis is still a common disease in children, especially those of immigrant families. Prevention and diagnosis rest on the plain chest film which should remain the first step of the work-up. Apart from cerebromeningeal complication, CT scan is also useful for evaluating chest lesions including mediastinal lymphadenopathies and lung parenchyma involvement. CT scan combined with endoscopy ensures detection of complications including bronchogenic dissemination. With a few cases as illustrations, the role of roentgenographic investigations in the management of pediatric tuberculosis is outlined. PMID- 1616244 TI - [A retrospective study of preadoption x-ray findings in young children at the Social Child Aid: value and limitations]. AB - French law requires that children awaiting adoption undergo full medical evaluation to detect anomalies which may influence decisions concerning adoption. As part of this evaluation, all infants admitted to the Saint-Vincent-de-Paul Preadoption Center in Paris undergo roentgenographic evaluation including frontal and lateral films of the skull, a frontal chest film, a frontal view of the pelvis, and frontal films of one upper limb and one lower limb. A study of the one hundred most recent evaluations, carried out in infants aged 1 to 14 months, disclosed 16 roentgenographic anomalies. Five of these anomalies were already known prior to the evaluation, 2 did not give rise to additional investigations, and 9 led to additional tests, a change of therapy or subsequent radioclinical monitoring. Among the six films taken in each patient, only the frontal views of the chest and pelvis proved informative. Screening using these two roentgenograms only is recommended, with other roentgenograms being performed if called for on the basis of clinical findings. PMID- 1616245 TI - [Spa treatment in pediatric pneumo-allergology and ENT]. AB - Each year in France, 42,000 children receive spa therapy, which is covered by the national health care insurance system. In over three cases out of four, the treatment is ordered by the child's physician for respiratory tract disease which fails to respond adequately to conventional therapy. Asthma, recurrent bronchitis, and spasmodic cough are the main indications in pneumo-allergology; seromucous otitis media, naso-sinusitis and refractory pharyngitis are the most common pediatric ENT diseases treated in spa centers. The two main types of mineral water used are sulfur-rich waters in patients with prominent infection and chloride and bicarbonate-rich waters when allergy is the main problem. Experimental studies point to the fact that these waters have immunomodulating effects. However, other therapeutic interventions in spa centers, including rehabilitation and health education, also play a role. Evaluations of spa therapy for respiratory tract diseases carried out by government agencies have demonstrated decreases in school absenteeism and above all in the use of drugs in treated patients. The future of pediatric spa therapy will likely depend on the development of preventive interventions in spa centers. PMID- 1616246 TI - [Respiratory infections: germs sensitive to cefaclor]. PMID- 1616247 TI - [Cerebral arteriovenous malformations in a probable familial form of Rendu-Osler disease]. AB - Cerebral arteriovenous malformations with neonatal manifestations are infrequent and virtually always fatal. Heart failure with an intracranial bruit is the most common presentation. Exceptionally, the aneurysm is a manifestation of Rendu Osler-Weber syndrome which is inherited on an autosomal dominant basis. Development of cerebral arteriovenous malformations occurs very early as demonstrated by the discovery of two aneurysms with major repercussions on the cerebral parenchyma in a female with severe prematurity. Pregnant women with suspected Rendu-Osler-Weber syndrome should undergo ultrasound studies targeted at identifying untreatable cerebral lesions antenatally. PMID- 1616248 TI - [Imerslund-Najman-Grasbeck anemia. Apropos of a case]. AB - Imerslund-Najman-Grasbeck anemia is an infrequent disease with an autosomal recessive pattern of inheritance. The characteristic anomaly is selective malabsorption of vitamin B12 by the ileal mucosa. Diagnosis rests on a positive family history and on the demonstration of megaloblastic anemia with proteinuria. The proteinuria is due to glomerular dysfunction with mesangial proliferation. Management rests on lifelong parenteral administration of vitamin B12. A case of Imerslund anemia with a favorable outcome under vitamin B12 treatment is reported. PMID- 1616249 TI - [Tumoral calcinosis. Apropos of a further case in a child]. AB - Tumor-like calcinosis is an infrequent condition whose etiology is poorly understood. Calcifications develop in the subcutaneous tissue neighboring the large joints. All age groups can be affected, although the disease is more common before the age of twenty years. A new case of tumor-like calcinosis in an eight year-old girl is reported here. A huge mass in the right hip region and a smaller mass around the right elbow were found. Biologic studies revealed increased serum phosphorus levels with normal serum calcium levels. Roentgenograms confirmed the diagnosis of tumor-like calcinosis by showing calcified masses independent from the bones of the neighboring joint. Management consisted in complete removal of both masses. Outcome was favorable. In this patient's family, the disease appears to be inherited according to a dominant pattern, although recessive autosomal transmission is believed to be more common. PMID- 1616251 TI - [School physician and rhythms of schoolchildren's life]. AB - The common occurrence of chronic fatigue among schoolchildren raises questions concerning sleep requirements and desirable daytime activity schedules in growing children. Several practical situations including inadequate sleep time, irregular sleeping hours, and lack of synchronization of activities and daytime biological periodicity are described. The inadequate attention given to these needs by families and society require widespread repeated diffusion of clear, short educational messages in order to improve the well-being of children. PMID- 1616250 TI - [Mobius syndrome and bilateral chorioretinal coloboma]. AB - A child with palsy of the right facial nerve and bilateral palsy of the VIth, IXth and XIIth cranial nerves, dysfunction of the VIIIth cranial nerve, facial malformations and bilateral equinovarus was diagnosed on the basis of these features as having Moebius syndrome. Ocular studies disclosed congenital cataract and chorioretinal coloboma in both eyes. These ocular abnormalities have not previously been described in Moebius syndrome. This paper discusses whether the coexistence of these two types of anomalies may be due to occurrence of a break in the primitive internal carotid and trigeminal arteries between the fourth and fifth postconceptional weeks, causing maldevelopment of the choriocapillary and impairing neuron differentiation in cranial nerve nuclei. PMID- 1616252 TI - [Medical language and communication with children: psycho-ethical aspects]. PMID- 1616253 TI - [Therapeutic evaluation of Mormoiron attapulgite in acute diarrheas of infants and children. A multicenter study in controlled liberal practice versus placebo in 113 patients]. AB - A placebo-controlled multicenter study was carried out to evaluate the effectiveness and safety of Actapulgite in infants and children with acute diarrhea. One hundred and thirteen patients, with a mean age of 28 months, were enrolled by pediatricians in the office. As recommended during acute diarrhea, the dosage of Actapulgite was doubled during the first three treatment days (2 to 4 packets a day according to the patient's weight), and reduced by half thereafter. The main effectiveness criteria was passage of the first normally formed stool, which denotes normalization of intestinal transit time. The first normally formed stool was recorded after two days of treatment with Actapulgite and was followed, on the next day, by a second normal stool, denoting complete recovery. The greater effectiveness of Actapulgite as compared with the placebo was demonstrated by the fact that both the first and the second normally formed stools were passed one day earlier with the active treatment (p = 0.01 and p = 0.002, respectively). In addition, resumption of a normal diet occurred significantly earlier with Actapulgite (4.4 days) than with the placebo (5.1 days). In addition to being effective, the study drug proved remarkably well tolerated. This study is especially valuable because of its office setting and the use of exclusively clinical criteria with a strict methodology. PMID- 1616254 TI - Palpation of peripheral pulses: a difficult art. PMID- 1616255 TI - An insight into Dupuytren's contracture. AB - Dupuytren's contracture is a deforming, fibrotic condition of the palmar fascia which has confounded clinicians and scientists since the early descriptions by Guillaume Dupuytren in 1831. It predominantly affects elderly, male caucasians, has a hereditary predisposition and has strong associations with diabetes, alcohol consumption, cigarette smoking and HIV infection. The major morphological features are an increase in fibroblasts, particularly around narrowed fibroblasts; a finding consistent with localised ischaemia. During ischaemia, adenosine triphosphate (ATP) is converted to hypoxanthine and xanthine, and endothelial xanthine dehydrogenase to xanthine oxidase (alcohol also mediates this change, a finding of particular relevance given the association of Dupuytren's contracture with alcohol intake). Xanthine oxidase catalyses the oxidation of hypoxanthine to xanthine and uric acid with the release of superoxide free radicals (O2-), hydrogen peroxide (H2O2) and hydroxyl radicals (OH.). These free radicals are highly reactive, with half-lives in the order of milliseconds and are toxic in high concentrations. A potential for free radical generation in Dupuytren's contracture was elicited by finding a sixfold increase in hypoxanthine concentrations in Dupuytren's contracture compared with control palmar fascia. In vitro studies affirmed the toxic effects of oxygen free radicals to Dupuytren's contracture fibroblasts, but also showed that, at lower concentrations (concentrations similar to those likely to occur in Dupuytren's contracture), free radicals had a stimulatory effect on fibroblast proliferation. Cultured fibroblasts were found to release their own O2-. These endogenously released free radicals were also found to be important in fibroblast proliferation. The collagen changes of Dupuytren's contracture were examined. The results established that fibroblast origin was unimportant, but that inhibition of type I collagen production at high fibroblast density accounted for the increase in type III/I collagen ratios observed by previous investigators. These biochemical and morphological observations throw new light on Dupuytren's contracture. They suggest that age, genetic and environmental factors may contribute to micro vessel narrowing with consequent localised ischaemia and free radical generation. Endothelial xanthine oxidase derived free radicals may both damage the surrounding stroma and stimulate fibroblasts to proliferate. Proliferating fibroblasts lay down and contract collagen in lines of stress.Progressive fibroblast proliferation and deposition of collagen is likely to encourage further microvessel narrowing with a positive feedback effect consistent with the progressive nature of the condition. PMID- 1616256 TI - Hand surgery requirements in an average sized district general hospital. AB - To estimate the overt need for hand surgery in an average sized district general hospital and to assess the resources required to meet this need, data were collected prospectively on all new trauma and elective patients presenting from 1 June to 30 November 1989 to the Derby Hand Unit, Derbyshire Royal Infirmary, Derby. In all, 1740 new patients with hand disorders (1082 trauma and 658 elective) were seen. All were followed up for 6 months or until discharge. Based on the Derby Hand Unit practice, the overt need for hand surgery in an average sized district general hospital was estimated and the resources required to satisfy this need were defined. Such a hospital serving a population of 250,000 should expect about 23 new trauma patients and 17 new elective patients each week. To service this demand requires between three and six outpatient clinics, between three and eight inpatient beds and three operating sessions each week. The net annual cost of such a service in 1989-1990 would be 318,753 pounds. PMID- 1616257 TI - Should we palpate foot pulses? AB - Palpation of foot pulses is traditionally used to evaluate patients with arterial disease. This study investigated observer variation in assessment of pedal vessels by pulse palpation and Doppler auscultation. A series of 33 claudicant patients and five controls were examined by a consultant, registrar, SHO and nurse. Dorsalis pedis (DP) and posterior tibial (PT) pulses were palpated and were then examined by Doppler with measurement of systolic pressures. CONTROL GROUP: No disagreement in DP pulses. However, all observers agreed on the presence of a PT pulse in only 70% of limbs. Claudicants: There was better agreement in palpation of the DP pulse (all observers agreed in 67% of limbs), than the PT pulse (all agreed in 53%). This suggests that the DP pulse is easier to palpate than the PT (P less than 0.05). By contrast there was better agreement on Doppler signals from the PT artery, all agreed in 78% of limbs; compared with the DP artery, all agreed in 58% (P less than 0.01). Pressure measurements by the observers agreed to within +/- 0.15 in 88% of claudicant and 100% of control limbs. Pedal pulse palpation in patients with arterial disease is subject to substantial observer error. Doppler pressure measurement is preferable unless pulses are bounding. PMID- 1616258 TI - Peripheral pulse palpation: an unreliable physical sign. AB - Fifty observers, including two fully trained vascular surgeons, were asked to determine the presence or absence of the femoral and distal pulses of four patients with peripheral vascular disease and one asymptomatic subject (50 pulses assessed). Pulses felt by both vascular surgeons were deemed to be palpable. Among the other observers, the sensitivity of palpation was 95% or over for the femoral pulse, but 33% to 60% for observers of varying experience feeling for the posterior tibial pulse. Up to 20% false-positive observations were reported. Disease was diagnosed in over 10% of examinations of healthy limbs and was missed in over 10% of symptomatic limbs. The accuracy of pulse palpation was strongly correlated with the systolic blood pressure in the underlying artery. Accuracy was greater among more experienced observers, suggesting that careful teaching of this skill is likely to be beneficial. Even so, pulse palpation alone is an unreliable physical sign and should only be used in combination with objective measurements as a guide to clinical management. PMID- 1616259 TI - The prognostic value of nucleolar organiser regions in colorectal cancer: a 5 year follow-up study. AB - Nucleolar organiser regions (AgNORs) are loops of ribosomal DNA which reflect the cellular activity or malignant potential of the cell and are identified by a specific staining technique. The purpose of this study was to assess the prognostic value of AgNORs in colorectal cancer and to compare it with other accepted prognostic methods. We studied 164 patients who were surgically staged for colorectal cancer and who had complete follow-up data available for 5 years. Using a highly specific silver staining and counting technique each patient was given an AgNOR score. There were 5 Dukes' C tumours, 108 were Dukes' B and 5 were Dukes' A. No cancer deaths occurred in patients with Dukes' A tumours. The incidence of well-differentiated, moderately-differentiated and poorly differentiated tumours was 37.2%, 53.7% and 9.1%, respectively. Non-survivors had significantly higher AgNOR scores compared with survivors (mean value +/- SD, 14.2 +/- 0.9 vs 8.2 +/- 0.6, P less than 0.0001). In a regression analysis model AgNOR score was the most significant individual variable for predicting survival (chi 2 = 15, P less than 0.01) when compared with Dukes' classification, histological grade, tumour depth or vascular invasion. PMID- 1616260 TI - Does surgical experience influence mastectomy complications? AB - Mastectomy remains the most commonly performed surgical procedure for breast cancer, and complications such as infection or wound breakdown (which may relate to the experience of the operator) could expensively prolong hospital stay and retard the administration of additional therapy. We examined the complications, hospital stay and cost of therapy of total mastectomy and axillary node clearance in 164 women, comparing these between four grades of surgeon: registrar (67 operations), senior registrar (58), part-time consultant (21) and professor (18). Our policy, for local reasons, was to perform mastectomy whenever possible rather than select lesser surgical or non-surgical management options. There was no significant difference between operators when the percentage of seromas requiring aspiration (9, 3, 5, 6), infection (16, 7, 23, 11), or wound breakdown (7, 3, 5, 6) were compared. Neither the length of hospital stay (9.3 +/- 6.9, 8.2 +/- 4.7, 9 +/- 7.3, 9.2 +/- 11.2 days), nor cost (2005, 1939, 1966, 1927 rands) differed. Surgical experience did not significantly influence mastectomy complications. PMID- 1616261 TI - Non-specific abdominal pain: the resource implications. AB - Non-specific abdominal pain (NSAP) is responsible for a significant proportion of emergency surgical admissions with resultant resource implications. The extent of the problem was assessed in a consecutive group of 100 patients, aged between 15 and 35 years, admitted with lower abdominal pain to one general surgical firm. No less than 67 of these patients (67%) were diagnosed as having NSAP (13.29% of all general surgical admissions), most (75%) being female and having a mean hospital stay of 4.1 days. Only 11 patients (11%) had appendicitis and the remaining 22 had miscellaneous gynaecological, urological or gastrointestinal problems. Detailed analysis of the resources used revealed that the mean cost to the NHS of each case of NSAP was 807 pounds, the bulk of which was attributable to the hospital stay. Wider assessment of the problem (by means of postal questionnaire) suggests that the cost to the NHS in Wales is in the region of 6 million pounds per year and may be over 100 million pounds per year in the UK as a whole. PMID- 1616262 TI - Carcinoma of the major salivary glands. AB - The results of a prospective survey of planned management of 28 primary carcinomas of the parotid, and five primary carcinomas of the submandibular gland over a period of 22 years are discussed. High- and low-grade carcinomas are distinguished and less radical treatment for the latter appears justified. PMID- 1616263 TI - Use of disposable skin staplers for bowel anastomosis to reduce laparotomy time in war. AB - Laparotomy for penetrating wounds to the abdomen is demanding in terms of time, skill and resources. Any modification of existing techniques that will lessen these demands will be of benefit at surgery in forward areas in war. A previous paper (1) compared a method of small bowel anastomosis using disposable skin staplers with a two-layer handsewn anastomosis using fresh pig ileum. The stapled method was both significantly faster to perform and mechanically superior. In two further studies on a total of 12 pigs the stapled method has been compared with a single-layer and a double-layer handsewn small bowel anastomosis. All 12 pigs recovered from laparotomy without complication. Construction times were recorded. The quality of healing of the anastomoses was assessed by clinical observation, post-mortem and histological examination, and tensiometry. The skill required to perform the stapled anastomoses was estimated subjectively. The stapled technique was consistently faster than the handsewn methods. A Kolmogorov two-sample test showed an improvement in times when comparing the stapled method with the single layer, with a significance of P = 0.05. An improvement was also seen when the stapled method was compared with the double layer, with a significance of P = 0.01. There was no statistically significant difference between the construction times for the two handsewn methods. There was no evidence of anastomotic failure or haematoma at post-mortem and no adverse reaction to the metal staples. No features were identified on histology to indicate impaired healing with the stapled method. Tensiometry of the anastomoses showed that the stapled anastomosis is as mechanically reliable as the handsewn anastomosis. The level of skill required to perform the stapled anastomosisis judged to be within the capabilities of relatively junior surgeons once the technique has been mastered in an anastomosis workshop. PMID- 1616264 TI - Audit of 200 consecutive aortic aneurysm repairs carried out by a single surgeon in a district hospital: results of surgery and factors affecting outcome. AB - It has been suggested that surgery for abdominal aortic aneurysm (AAA) be confined to designated centres. A prospective audit of 200 consecutive AAA repairs at a district general hospital was performed between 1981 and 1990. The 30-day mortality rates for elective, symptomatic and ruptured aneurysm repair were 1.4%, 3.5% and 30%, respectively. The major factor affecting outcome after the mode of presentation was the age of the patient, with 30-day mortality rates for emergency treatment increasing from 21% (age range 60-69 years) to 42% (age range 70-79 years). This mortality rate for ruptured aneurysms is an underestimate, with two-thirds of patients with rupture dying before reaching hospital and some patients dying in hospital undiagnosed. The major contribution to improved overall mortality would therefore be detection before rupture (usually by ultrasound) and improved diagnostic accuracy. Many patients with ruptured aneurysms had symptoms for only a short period before presentation (42% for less than 6 h) and required urgent surgery (26% reached theatre within 1 h). These two factors make long-distance transfer of these patients an unrealistic option. The concentration of this type of surgery in relatively few centres will distance the patient from their relatives and reduce the opportunity for the majority of junior doctors to acquire an understanding of the presentation, natural history and management of aortic aneurysms. This understanding when combined with a screening programme is likely to have a far greater impact on the overall mortality from AAA than restricting the centres for surgical treatment. PMID- 1616265 TI - Care of road traffic accident victims in a district general hospital. AB - It has been suggested that 20-33% of trauma related deaths are preventable. The Accident and Emergency Department of Luton and Dunstable Hospital, therefore, set out to examine its own performance and to attempt to highlight areas of possible improvement. The department sees 65,851 new patients per annum, 3936 of these were victims of road traffic accidents (RTA). There were 184 patients admitted and six died. One death was considered preventable; shortcomings were noted with delay in availability of services. It is recommended that early assessment by experienced clinicians and easy access to theatre facilities and diagnostic imaging be available in district general hospitals to improve the quality of care for trauma victims. PMID- 1616266 TI - Six hundred patients with gallstones. AB - A total of 610 patients with gallstones were treated over an 8-year period in a single surgical unit. Of these patients, 384 had cholecystectomy, 86 surgical duct exploration and 140 endoscopic sphincterotomy. Four patients died after cholecystectomy (1%), but there were no deaths after the treatment of duct stones. The proportion of patients with duct stones having endoscopic sphincterotomy with the gallbladder in situ rose considerably during the 8-year period, from about 20% to 75%. Gallstones tend to present in the elderly as duct stones, and in the young as gallbladder stones. The majority of patients over 75 years of age had endoscopic sphincterotomy, whereas the younger patients were usually treated surgically. PMID- 1616267 TI - Primary carcinoma of the gallbladder: a 10-year experience. AB - New developments in the management of gallstone disease, and particularly percutaneous and extracorporeal treatments that leave the mucosa intact, have renewed interest in the relationship between cholelithiasis and carcinoma. These treatments are both available in our hospital and to examine this question we studied the patients presenting between 1980 and 1990 with gallbladder cancer. The study comprised 21 patients with histologically proven carcinoma. The M:F ratio was 1:4 with a mean age of 76 years. Gallstones were present in 18 patients (85.7%). Ten patients remain alive today and in the 11 who died the median survival was 4 months. A preoperative diagnosis was made by ultrasound in only two patients. The lack of a preoperative diagnosis in the majority of patients is clearly a cause for concern and while our figures, like other series, do not establish a causal relationship with gallbladder carcinoma, it is vital to be diligent in the follow-up of high-risk patients (stones greater than 3 cm) with intact gallbladder mucosa after the treatment of stone disease. PMID- 1616268 TI - Assessment of burn injury in the accident and emergency department: a review of 100 referrals to a regional burns unit. PMID- 1616269 TI - Control of presacral bleeding in rectal surgery. PMID- 1616270 TI - Application of the laryngeal mask airway to thyroid surgery and the preservation of the recurrent laryngeal nerve. PMID- 1616271 TI - Application of the laryngeal mask airway to thyroid surgery and the preservation of the recurrent laryngeal nerve. PMID- 1616272 TI - Prevention of occupational transmission of HIV in the ENT clinic. PMID- 1616273 TI - Contamination of underwater seal drainage systems in thoracic surgery. PMID- 1616274 TI - Assessment of the use of disposable skin staplers to reduce laparotomy time in penetrating ballistic injury of the abdomen. PMID- 1616276 TI - Coloproctology--a specialty in transition. PMID- 1616275 TI - Dilemmas in providing a vascular surgical service. PMID- 1616277 TI - Should surgical services be ringfenced? PMID- 1616278 TI - How to improve communication between the fellowship and the college. PMID- 1616279 TI - Surgical training. PMID- 1616280 TI - Senior registrars in general surgery. PMID- 1616281 TI - A new method for calculation of height centiles for preadolescent children. AB - A new method of calculation of cross-sectional attained height centiles is proposed. This exploits the variance-stabilizing transformation, which has the form log(a+b height) up to age 11 years. Residuals of transformed height about the expected value for age are antilogged to give a single Gaussian distribution from which centiles can be calculated. In contrast to previous methods the standard errors of the centiles can be estimated without imprecise adjustment for smoothing. The parameters a and b of the transformation do not need precise estimation and the method can be used for population subgroups from which large samples cannot be obtained. PMID- 1616282 TI - An abnormal concentration of cases of Rendu-Osler disease in the Valserine valley of the French Jura: a genealogical and demographic study. AB - An important concentration of patients with Rendu-Osler disease occurs in the Valserine valley of the French Jura. A study of marriages shows that, in spite of its somewhat remote location, the valley cannot be considered an isolate, but that, on the contrary, exogamy is widely practised. Only 17.8% of the genes of inhabitants during the present century can be traced to the original population, but persons affected with the disease belong to a subgroup of the population which has lived in the villages for more than 10 generations. All the patients in 85 sibships are related. The smallest number of originator couples who lived at the beginning of the eighteenth century amounts to 16, the unique originator may therefore have lived approximately four generations earlier. However, as other patients who lived at the periphery of the Valserine valley do not appear to be related to any patients living in the valley, and because there has been considerable immigration into the valley, a number of hypotheses to explain the distribution of the disease in the region remain possible. PMID- 1616283 TI - Secular change in the growth and development of Han children in China. AB - This paper reports the secular change in physical growth and development of Han children in 12 Chinese metropolitan cities including Beijing, Tianjing, Shanghai, Jinan, Harbin, Shenyang, Changchun, Nanjing, Hangzhou, Wuhan, Guangzhou, and Chengdu. Based on a recent national survey of 14,688 healthy schoolchildren, aged 7-18 years, and together using the historical records of healthy schoolchildren as secondary data source, this study found a secular change in the growth and development of Chinese children and youth. In every decade between the 1950s and 1985 the average height increased by 2.66 cm (range 1.78-3.77) for boys and 2.40 cm (range 1.72-3.76) for girls, and the average weight increased by 1.64 kg (range 1.28-2.63) for boys and 1.14 kg (range 0.63-2.01) for girls in the 12 cities. In the last decade from the 1970s to 1985, the height and weight increments were highest in Beijing, Jinan, Shenyang and Shanghai. In addition, the increments were higher during the peak growth years than during other periods of growth. In the 30 years studied, the ages of maximum growth velocity were advanced, and they were 1 or 2 years earlier in 1985 than in the 1950s in most cities. When compared with the data from the 1930s the results indicate that, during the last half-century, height increased by 1.12-2.66 cm per decade for boys and 1.42-2.67 cm/decade for girls, while weight increased by 0.56-1.27 for boys and 0.65-1.18 kg for girls in Beijing, Shanghai, Nanjing, Hanzhou and Guangzhou. PMID- 1616284 TI - Estimation of stature from second metacarpal length in Japanese children. AB - A relationship between stature and second metacarpal length was examined by means of a linear regression for sex, skeletal age and locality in 2056 children aged 6 19 years in five districts of Japan. Significant differences (p less than 0.05) were found for the regression of two measurements between immature and mature groups according to the TW2 method. Few significant differences were found in the regression with sex and locality in both immature and mature groups. Stature could be estimated from second metacarpal length with standard errors of 44mm in the immature group and 40mm in the mature group. Furthermore, from the bone length and TW2 age, stature could be estimated with a standard error of 38mm for each sex in combined groups. These figures are similar to the variability in stature at a given age and comparable to reliability of estimates from long bones. The second metacarpal length may be a reliable and practical marker in children for the estimation of stature by means of a general formula regardless of sex and locality in a population. PMID- 1616285 TI - Population genetics of coagulation factor XIIIB in three ethnic groups of Singapore. AB - The distribution of plasma coagulation factor XXIIB polymorphism was determined by PAG isoelectric focusing and immunoblotting in a group of 670 subjects comprising 375 Chinese, 110 Malays and 185 Indians. The frequencies of FXIIIB*1, FXIIIB*2, and FXIIIB*3 were found to be 0.27, 0.03 and 0.70 in the Chinese; 0.33, 0.05 and 0.64 in the Malays and 0.58, 0.08 and 0.33 in the Indians. The phenotypic distribution of FXIIIB alleles was at Hardy-Weinberg equilibrium in all three populations. A two-dimensional principal-components analysis on the basis of three common alleles at the FXIIIB locus among 19 populations, so far studied, clearly differentiates the Negroid, Mongoloid and Caucasoid populations into three major groups with the exception of Amerindians (Minnesota) and US Blacks showing some Caucasoid influence. PMID- 1616286 TI - Vertebral body diameters and sex prediction. AB - As a direct consequence of the generally larger body size of the male, it is reasonable to expect the adult human vertebral column to display sexual dimorphism. However, there is a distinct paucity of literature concerning sex related variation in vertebral dimensions. This study examines the accuracy with which sex may be predicted from vertebral body diameters. In a sample selected from a documental skeletal series, sex could be correctly assigned with an accuracy approaching 90%. This degree of sexual differentiation is of value for both the forensic and archeological identification of human skeletal remains. An interesting relationship was noted between the degree of expression of sexual dimorphism and the role of each area of the vertebral body in body weight transfer. The posterior aspect of the vertebral body is involved in the transmission of body weight both vertically and laterally from the transverse processes. This area was consistently less dimorphic than the anterior region of the vertebral body, which is more concerned with the transfer of body weight from the vertebra above. PMID- 1616287 TI - Red cell enzyme and serum protein types in the Watut Anga of Papua New Guinea. AB - Historically, the Angan populations of Papua New Guinea have maintained a strong isolation and absorbed limited genes from their neighbours. This lack of intermixing is reflected in their relatively homogeneous cultural, linguistic and genetic profiles. We have determined the electrophoretic variation at 26 red cell enzyme, serum protein and haemoglobin loci in the Watut Anga, a splinter group occupying the Upper Watut Valley of Morobe Province. Their genetic profile reveals the lack of a number-of variants, such as PGM2*10 and MDH*3, known to exhibit high frequencies in other highland populations. The average heterozygosity in the Watut is also much lower when compared with other Papua New Guinean populations. Their present numerical strength notwithstanding, it appears that the Angan populations have experienced population bottlenecks in their evolutionary history which may have accentuated their genetic divergence from other Papua New Guinean populations. PMID- 1616288 TI - A new method of deriving velocity and acceleration curves for height from the kernel estimation of distance. AB - Further development of the optimal kernel (OK) method of growth curve analysis of Gasser et al. (1984b) is presented with the aim of eliminating the necessity of repeated changes in bandwidth to suit different characteristics of the velocity and acceleration curves at varying ages. After using the OK method to obtain a distance curve for height, we introduce a new method (VADK) to derive velocity and acceleration curves from the fitted distance curve. The results from growth data on 16 boys and 15 girls from the Edinburgh Longitudinal Study are presented in a preliminary test of this method in comparison with the OK estimation. PMID- 1616289 TI - A two-level cross-sectional model using grafted polynomials. AB - A new statistical model is proposed for the analysis of hierarchically structured cross-sectional growth data, especially for where measurements are made over long age ranges. The model combines a two-level model with grafted piecewise polynomials, to make efficient use of available data. PMID- 1616291 TI - Height growth of adolescent German boys and girls. AB - Longitudinal annual height measurements of 46 boys and 47 girls from Dortmund, Germany, are used to derive 10 parameters concerning the adolescent growth spurt of height. Out of three mathematical models applied to our height data, model 1 of Preece and Baines (1978) proved most suitable. Data of mean heights at age 9 and 10 of the boys and girls of this study do not differ from those of another representative cross-sectional study of our institute. The values of the 10 parameters agree with the data of studies from other countries. This work contributes original German data to the international data on adolescent growth spurt of height. PMID- 1616290 TI - Gene diversity and estimation of genetic admixture among Mexican-Americans of Starr County, Texas. AB - The Mexican-Americans of Starr County, Texas, classified by sex and birthplace, were studied to determine the extent of genetic variation and contributions from ancestral populations such as Spanish, Amerindian and West African. Using 21 genetic marker systems, genetic distance and diversity analyses indicate that subpopulations of Mexican-Americans in Starr County are similar, and that more than 99% of the total gene diversity (HT) can be attributed to individual variation within the population. Genetic admixture analysis shows the predominant influence comes from the Spanish, a lesser contribution from Amerindians and a slight one from the West Africans. The contribution of the ancestral population to various subpopulations of the Mexican-Americans of Starr County is similar. The Mexican-Americans of Starr County are similar to the Mexican population from northeastern Mexico. The history of admixture is apparently old enough to have brought the entire Mexican-American gene pool to Hardy-Weinberg equilibrium. There is no non-random association of alleles among the genetic marker systems considered in the present study, in spite of the fact that this population is of admixed origin. These results, in aggregate, suggest genetic homogeneity of the Mexican-Americans of Starr County, Texas, and point towards the utility of this population for genetic and epidemiological studies. PMID- 1616292 TI - Microevolution in Ferrara: isonymy 1890-1990. AB - The distribution of surnames in the population of the town of Ferrara, as it existed in the memory banks of the Municipality Computer in June 1990, was studied by sex, age and place of birth of residents. Random isonymy was studied separately in persons born before 1901, and in persons born in the nine decades thereafter, ending with the period 1981-90. Isonymy was higher in the older age groups studied. Also other indicators of the abundance of surnames in the distribution, the common ecological indexes derived from entropy, were calculated and compared between age groups. It was found that redundancy, as isonymy, is larger in older age classes than in younger classes. Surname effective number was defined as the inverse of isonymy corrected for sample size, and it was observed that it is practically identical with Fisher's alpha. It was then possible to separate random isonymy into two components, so that for sample size N its formulation becomes Ir = 1/alpha + 1/N It was found that in Ferrara alpha increased significantly in time, indicating enrichment of surnames in the population in the century 1890-1990. PMID- 1616293 TI - Developmental perspective of pulse rate, blood pressures and vital capacity in Chinese children. AB - Physiological development in Chinese children was analysed based on a national survey sample. Close to half a million children and adolescents, aged 7-18 years, from Han and 27 minority nationalities were assessed for pulse rate, systolic and diastolic blood pressure, and forced vital capacity in these 12 age groups. The factors of age, sex, race, and region (urban/rural, north/south) were analysed. P95 hypertension screening standard was established for each age group. These results were compared with research reports from world literature. PMID- 1616294 TI - Biological age in Italian adults: influence of social and behavioural factors. AB - This study investigated changes with age in biological characters in a sample of 571 Italian males aged between 25 and 64 years. The influence of environmental factors on inter-individual variation in physical efficiency was examined by biological age determination. Data on somatometric, physiometric, haematological variables, personal background and lifestyle, were collected. Principal-component analysis was used to study the patterns of relationship in these characters. Over 45% of the total variance is explained by the ageing process, but the secular trend also affects the variation of height and of height-related characters. Changes with age were investigated clustering the sample in eight 5-year classes: results are in agreement with previous findings in Western populations. Ten selected variables were transformed into biological age scores reflecting a man's status relative to his chronological age peers (Borkan and Norris 1980a). Biological age scores of subsamples characterized by different social and behavioural situations were compared. Occupation, educational level and physical activity seem to have the greatest influence on biological age status. The intensity or duration of some habits can induce a clear trend in biological age scores. Results suggest that the environmental influence could be related to the interindividual differences in physical efficiency and to the increase in variability with age observed for some characters. PMID- 1616295 TI - Net mechanical efficiency during stepping in chronically energy-deficient human subjects. AB - Mechanical efficiency during a step test was measured in chronically energy deficient (CED) individuals and compared to well-nourished subjects using a whole body indirect calorimeter. The CED group had significantly higher net mechanical efficiencies than the well nourished subjects. This was also evident in the 15% lower energy costs observed in the CED subjects when expressed as a percentage of the predicted data. Factors such as a higher proportion of slow muscle fibres as well as a greater ergonometric efficiency may contribute to the observed higher muscular efficiency aiding conservation of energy expenditure in these individuals. PMID- 1616296 TI - Skeletal maturity of the hand and wrist in Chinese children in Changsha assessed by TW2 method. AB - Skeletal maturity of 2122 normal children aged 2-20 years in the southern Chinese city of Changsha have been assessed by the TW2 score method. These mean bone ages are lower than the British standards up to puberty and thereafter higher than the British standards. PMID- 1616297 TI - [Prognostic factors of germinal tumors of the testicle]. AB - Certain risk factors need to be defined in order to evaluate the risk of recurrence during the follow-up of patients with stage I non-seminomatous germ cell tumours of the testis. Their respective value was studied in order to adopt those suggestive of disease progression. In contrast, in the more advanced stages of the disease, it is difficult to define a single attitude due to the variable prognostic factors taken into account by different authors. PMID- 1616298 TI - [Surgical modalities in germinal tumors of the testicle]. AB - Radical orchidectomy via a kelotomy incision in the first diagnostic and therapeutic procedure in germ cell tumours of the testis. The traditional extensive bilateral lymph node dissection responsible for ejaculation failure and significant complications has now been replaced by limited lymphadenectomies using nerve-sparing and nerve-preserving techniques with a simpler post-operative course. The resection of residual masses after chemotherapy should be performed as a true lymphadenectomy and is associated with certain difficulties, particularly in advanced seminomas. PMID- 1616299 TI - [Therapeutic modalities for germinal testicular tumors, excluding surgery. Radiotherapy--chemotherapy]. AB - There are two other treatments for germ cell tumours of the testis apart from surgery: radiotherapy and chemotherapy. Radiotherapy is ideally administered with a linear accelerator delivering photons and electrons. The dose is well established and smaller volumes are now irradiated. The precision is increased by CT and by the use of personalized shields. Radiotherapy is indicated in pure seminomas, with two exceptions: rare seminomas with a large tumour mass (2%), rare palliative indications for non-seminomatous germ cell tumours. Chemotherapy, following the progress due to the combination of vinblastine and bleomycin, has been based, for the last 10 years, on cisplatin, which must be administered at the correct dose. VP 16, ifosfamide and other drugs have also been introduced. In forms with a poor prognosis and depending on the clinical course, this chemotherapy should be administered at high doses with the protection of autologous bone marrow transplantation. This requires an appropriate infrastructure and a well trained team. The short-term and long-term effects of radiotherapy are more clearly defined than effects of chemotherapy. PMID- 1616300 TI - [Therapeutic indications for germinal testicular tumors]. AB - The therapeutic indications for germ cell tumours of the testis depend on the histology (pure seminoma: 45%, non-seminomatous germ cell tumour: 55%), the extension and the severity of the prognosis. The well standardised approach to pure seminomas is less clear for non-seminomatous germ cell tumours. Stage I, IIAB pure seminomas (95 to 98% of cases) should be irradiated. The dose and target volume are adapted to prophylactic (I) and curative (II) objectives. Rare seminomas with a large tumour bulk should be treated with chemotherapy. Survival is close to 100%. Stage I non-seminomatous germ cell tumour offers several theoretical possibilities. Radiotherapy is not very popular and chemotherapy appears to be to aggressive, lumboaortic lymph node dissection is being replaced by new imaging modalities and simple follow-up requires a rigorous and disciplined approach. At the Val-de-Grace hospital (France) since 1987, we perform simple orchidectomy in favourable stage I disease: 80% are cured with no other treatment, 20% relapse and are cured by chemotherapy, in the unfavourable stage I cancers (histology, markers) or with uncertain follow-up, limited chemotherapy is performed (3 cycles of EP). Stage II and more advanced non seminomatous germ cell tumours are divided into moderate forms (IIA, B, III, IVL1) and major forms (IIC, IVL2, L3, H+, CNS+). In the exclusive infradiaphragmatic involvement of moderate forms, some authors propose bilateral lumboaortic lymph node dissection which is invasive surgery with an efficacy declining from 90% (IIA) to 50% (IIB). The majority of teams, particularly Val-de Grace, administer 3 or 4 courses of BEP followed by assessment (CT scan - markers) and salvage surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616301 TI - [The sexual future of patients cured of testicular cancer]. AB - The sexual future of patients cured of testicular cancer is a legitimate preoccupation due to the high rate of successful treatment for this disease. The psychological and functional aspects and the fertility before and after treatment of operated patients are reviewed and the least harmful solution is proposed for each handicap. The question of induction of new cancers by chemotherapy remains unanswered; a number of years of follow-up will be required before an answer can be proposed. PMID- 1616302 TI - [Nephrotoxicity of cisplatin]. AB - Cis-diamminodichloroplatinum or cisplatin is one of the most widely used antineoplastic agents in oncology, particularly in malignant testicular tumours. The administration of this potentially nephrotoxic drug requires certain precautions in order to avoid renal damage. Nephrotoxicity generally consists of an isolated and transient rise in plasma creatinine, occasionally acute renal failure and rarely end-stage renal failure. In a series of twelve patients (mean age: 26 +/- 8 years) operated for malignant testicular tumour and treated secondarily with a cis-diamminodichloroplatinum based chemotherapy protocol (cumulative doses ranging from 490 to 2,275 mg) and submitted to nephrological follow-up for 56 +/- 20 months after treatment, no cases of immediate or delayed acute renal failure or deterioration in renal function were observed. PMID- 1616303 TI - [Special issue devoted to testicular neoplasms]. PMID- 1616304 TI - [Epidemiology of testicular tumors]. AB - Testicular tumours are rare tumours affecting young adults (75% of tumours are diagnosed between the ages of 25 and 40 years). The descriptive epidemiological study of the data of the literature reveals a considerable improvement in the prognosis of testicular cancers, particularly since the introduction of cisplatin in the 1980. An epidemiological study conducted on a series of 200 testicular tumours treated at Val-de-Grace military hospital between 1979 and 1989 confirms this improvement with a mortality rate of 7.5% for all stages and histological types combined, with a follow-up of 2 to 12 years. PMID- 1616305 TI - [Cancer of the testicle: diagnosis]. AB - Although great progress has been made in the treatment of testicular cancer over recent years, little progress has been made in the detection of this disease. The time between the discovery of a scrotal swelling by the patient and the first consultation is still too long. The authors study the presenting symptoms of the disease and the clinical examination which have not changed since the description by Chevassu. Complementary investigations have become essential: particularly, ultrasonography and tumour markers. The place of magnetic resonance imaging has yet to be defined. The last step in the diagnostic work-up consists of exploratory orchidotomy. PMID- 1616306 TI - [Radical orchiectomy]. AB - The authors recall that exploratory orchidotomy remains an essential operation for the diagnosis of testicular cancer and orchidectomy constitutes the primary therapeutic procedure. The operative technique is described together with its intangible principles, its difficulties and its variants. The tumour markers are best assayed on a sample of cord blood. The insertion of a testicular prosthesis, which is usually well supported, decreases the psychological effects of castration and does not cause any delay in possible adjuvant treatment. PMID- 1616307 TI - [Anatomic pathology of testicular tumors]. AB - Pathological examination of testicular tumours demonstrates the heterogeneity of the histological types encountered. Germ cell tumours, with one or several components, represent 95% of all testicular tumours. The distinction between these various types is always based on morphological criteria, but may also be facilitated by the use of immunolabelling techniques on fixed sections. The local and regional extension and the distinction between seminomatous and non seminomatous germ cell tumours are important criteria in the subsequent therapeutic strategy. At the present time, there is no consensus concerning the selection of other histoprognostic criteria, which may be observed in the primary tumour it its metastases. Residual masses also have a variable histology and their pathophysiology is sometimes difficult to interpret. PMID- 1616308 TI - Exposure of applicators and residents to chlordane and heptachlor when used for subterranean termite control. AB - Research was conducted to assess dermal and respiratory exposure to applicators from chlordane and heptachlor used for subterranean termite control and exposure to residents of treated homes. Dermal exposure of 29 applicators was evaluated by using gauze pads attached to outer and inner clothing at selected body regions. Respiratory exposure of applicators was monitored with personnel-type air samplers worn during application periods. Air samplers were equipped with polyurethane foam plugs to trap airborne chlordane and heptachlor. Exposure of residents was measured by sampling ambient air of 19 homes treated with the termiticides. Electric air samplers equipped with foam plugs were used to monitor ambient air from the basement, the kitchen, and one bedroom at: 24 h prior to termiticide application, during application, and post-application at 24 h, 1 wk, and monthly for 6 mo. Applicator dermal exposure was estimated based on exposure rates to each body region. Respiratory exposure was estimated based on termiticide concentrations in the air and on the ventilation rate of a person doing light work. Residents' exposure was estimated based on the amount of termiticide present in ambient air. Results indicated that applicator exposure rates to chlordane and heptachlor were 2.54 and 1.88 micrograms/kg/h, respectively. Residents were exposed to less than 0.69 and 2.86 micrograms/m3 of chlordane and heptachlor, respectively. During this research, the application of termiticide containing chlordane and heptachlor posed minimal risk in terms of acute exposure to either the applicators or the residents of the treated homes. PMID- 1616309 TI - Family pesticide use in the home, garden, orchard, and yard. AB - This study examined family use of pesticides in the home, garden, orchard, and yard. Data were collected from 238 families in Missouri during telephone interviews from June 1989 to March 1990. Nearly all families (97.8%) used pesticides at least one time per year and two thirds used pesticides more than five times per year. More than 80% used pesticides during pregnancy and 70% used pesticides during the first 6 months of a child's life. The most common setting for family pesticide use was in the home, where 80% of families used pesticides at least once per year. This was followed by herbicide use to control yard weeds (57% of families) and insecticide use to control fleas and ticks on pets (50% of families). A substantial number of families also used pesticides in the garden or orchard (33%). Flea collars were the most popular pest control product (50% of families). Carbaryl or Sevin was also popular, with 28.2% of families reporting use. No-pest-strips (dichlorvos) and Kwell shampoo (lindane) were used by almost 10% of participating families. Examination of study data revealed that families limited exposure to pesticides for the mother during pregnancy and for children during the first 6 months of life. Families failed to recognize and reduce pervasive exposures associated with no-pest-strips and flea collars. PMID- 1616310 TI - Cytogenetic studies of herbicide interactions in vitro and in vivo using atrazine and linuron. AB - The herbicides atrazine and linuron, found in Wisconsin's groundwater, were tested alone and in combination, both in vivo and in vitro, to determine their individual and combined genotoxic effects. Human lymphocytes exposed in vitro to either 1 microgram/ml linuron or 0.001 microgram/ml atrazine showed little chromosome damage, whereas significant chromosome damage was observed in lymphocytes simultaneously exposed to 0.5 microgram/ml linuron and 0.0005 microgram/ml atrazine, suggesting at least an additive model. In another experiment, mice were fed 20 micrograms/ml atrazine, 10 micrograms/ml linuron, or a combination of 10 micrograms/ml atrazine and 5 micrograms/ml linuron in their drinking water for 90 days, after which bone marrow cells and cultured splenocytes were examined for chromosomal damage. None of the treatment groups showed chromosome damage in bone marrow, whereas the cultured splenocytes demonstrated damage in all treatment groups. These experiments suggest that, prior to assessing the risk of a herbicide, it may be necessary to test it in combinations which mimic the mixtures which would occur under field conditions, such as in contaminated groundwater. PMID- 1616311 TI - Sublethal effects of ethylene dibromide on wound healing and morphogenesis in Hydra oligactis. AB - Morphogenetic activity (budding region regeneration, foot regeneration, tentacle regeneration, spikes, separation, and waist) was observed in Hydra oligactis with two tandemly arranged gastric regions (2g hydras) following exposure to a commercial ethylene dibromide (EDB) mixture. First-stage budding hydras were selected for this study. Animals were deprived of food 24 h prior to grafting and observed at 24, 48, and 72 h after grafting. The artificial pond water (APW) group was not treated with any chemicals prior to grafting. The acetone/APW group was pre-exposed to a concentration of 20 mg/L of acetone/APW 24, 48, and 72 h prior to grafting and observed at 24 h intervals for a three-day period. The EDB: acetone/APW group was exposed to a mixture containing 5 mg/L of EDB and 15 mg/L acetone for 24, 48, and 72 h prior to grafting and observed at 24-hr intervals for three days. All animals were incubated at 19 +/- 2 degrees C. Ethylene dibromide caused a significant decrease in 2 degrees foot regeneration at the 72 h observation interval for animals pre-exposed to EDB for 48 and 72 h. There was also a significant correlation between pre-exposure and a decrease in the number of 2 degrees feet regenerated. Tentacle regeneration was significantly suppressed following a 24-h pre-exposure to EDB. Waists at the graft border significantly increased at the 48 and 72 h observation times and separation of the graft border appeared at 72 h after grafting following 72 h pre-exposure of the animals to the chemical. PMID- 1616312 TI - Impaired cortisol stress response in fish from environments polluted by PAHs, PCBs, and mercury. AB - The cortisol stress response to capture was investigated in two species of fish (Perca flavescens and Esox lucius) from sites polluted by high levels of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and mercury, and from reference sites in the St. Lawrence river system. Fish from the reference sites exhibited the normal elevation of serum cortisol in response to the acute stress of capture and had large pituitary corticotropes. In contrast, fish from the most polluted sites were unable to increase their serum cortisol in response to the acute stress of capture and their pituitary corticotropes were atrophied. These results suggest that a life-long exposure to chemical pollutants may lead to an exhaustion of the cortisol-producing endocrine system, possibly as a result of prolonged hyperactivity of the system. PMID- 1616313 TI - Time to death of mosquitofish (Gambusia holbrooki) during acute inorganic mercury exposure: population structure effects. AB - Times-to-death (TTD) of mother and offspring mosquitofish (Gambusia holbrooki) were examined during acute exposure to mercury concentrations of approximately 1.0 mg/L. Median TTD were more similar for fish sharing a common mother (defined herein as a sibship) and microhabitat during maturation than between sibships. Field populations may exhibit structure similar to that of these sibships. Correlations between broods (or other population subunits) and allozyme genotype could be responsible for transient, genotype effects noted during electrophoretic surveys attempting to measure population level response to toxicants. PMID- 1616314 TI - Comparative sensitivity of gametes and early developmental stages of a sea urchin species (Echinometra mathaei) and a bivalve species (Isognomon californicum) during metal exposures. AB - Bioassays were developed using sperm of a sea urchin (Echinometra mathaei), and sperm, embryos, and larvae of a bivalve species (Isognomon californicum). Sea urchin spawning was restricted to only a few months of the year and viability of sperm throughout the year varied from 5 to 75%. Sea urchin fertilization assays were affected by temporal variation in sperm viability. Spawning in this bivalve species occurs year-round and there is little temporal variation in sperm viability. Since stringent sperm:egg ratios are not required for the bivalve embryo and larval assays, these were less affected by variation in gamete quality. The relative sensitivity of the various assays were compared during exposure to three different metal pollutants: cadmium, copper, and tributyltin. Gametes and embryos were relatively resistant to cadmium toxicity, but larvae were very sensitive. With copper and tributyltin, sea urchin and bivalve fertilization assays were the least sensitive; and bivalve growth assays were the most sensitive, followed closely by the bivalve embryo assays. On the basis of sensitivity, ease and time required to conduct the assay, and salinity tolerance, the bivalve embryo assay was recommended as the overall single most reliable toxicity bioassay. However a multispecies, multidimensional approach using sperm fertilization assays as well as embryo assays should be employed, perhaps in a hierarchal manner. Larval growth assays were deemed too tedious and time consuming to be used routinely, but due to their high sensitivity, should still be considered as a valuable comparative tool. PMID- 1616315 TI - Failure of gas bladder inflation in striped bass: effect on selenium toxicity. AB - Young striped bass (Morone saxatilis) with uninflated gas bladders were less sensitive to selenate and more sensitive to selenite exposure than normally developing striped bass in 96-hour acute toxicity tests. Gas bladder inflation failure is a common problem in the culture of striped bass and some other species, and care should be taken to avoid the use of fish with uninflated gas bladders in research. PMID- 1616316 TI - Patterns of metal accumulation in Laminaria longicruris from Long Island Sound (Connecticut). AB - Laminaria longicruris de la Pyl. samples were harvested from Long Island Sound (Connecticut) from January 1985 to January 1986. Cadmium and copper content was determined by atomic absorption spectrophotometry from four tissue types; young blade, old blade, young stipe and old stipe. The results were statistically analyzed for differences in both type and age of tissue. Concentrations of cadmium were consistently lower than copper concentrations for all months and all tissue types. Statistically significant differences (p greater than 0.05) were found between the four tissue types for copper in the months of March, June, July, October and December, and for cadmium in the months of February, March, June, July, October and November. Young blade tissue and young stipe tissue were the tissues which most frequently found to be statistically different from the other tissues. Young stipe tissue had the lowest trace metal concentrations (1.3 mean ppm, dry wt. Cu, 0.22 mean ppm, dry wt. Cd). Young blade tissue had significantly higher metal values in comparison to the other tissues for the months of June and October. Old tissue of L. longicruris is the most suitable for use in biomonitoring of trace metals due to the relatively little variation in metal content that was found throughout the study period. PMID- 1616317 TI - Cadmium resistance in Gammarus pulex (L.). AB - The ability of Gammarus pulex to develop cadmium resistance through physiological acclimation was investigated. Organisms were found to be significantly more tolerant to acute cadmium toxicity after pre-exposure to sublethal concentrations of cadmium and zinc. The induced elevation in cadmium tolerance was shown to be associated with an increase in the body concentration of a metallothionein-like protein. Pre-exposure had no apparent effect on cadmium uptake, although it did influence the distribution of cadmium within the organisms. Whereas pre-exposure to low levels of zinc and cadmium increased cadmium tolerances in acute tests, it had no observable effects on sublethal responses measured during chronic exposure. PMID- 1616318 TI - The 70 kD heat shock protein (hsp 70) in soil invertebrates: a possible tool for monitoring environmental toxicants. AB - The expression of hsp 70 after heat shock or exposure to heavy metals/molluscicides was investigated by fluorography or immunoblot in three diplopods (Glomeris marginata, Cylindroiulus punctatus, Tachypodoiulus niger), two slugs (Deroceras reticulatum, Arion ater), and one isopod (Oniscus asellus). In O. asellus, hsp 70 expression occurred after heat shock and also after lead treatment, whereby a solution of 100 mg/kg Pb2+ was sufficient. Animals of the same species taken from a heavy metal polluted site in the vicinity of a lead/zinc smelter also showed the presence of hsp 70. The comparison of laboratory and field experiments demonstrated the suitability of O. asellus for monitoring tests. In contrast, the blot pattern after contamination with 1,000 mg/kg Pb2+ (in the mentioned diplopods) or different concentrations of the molluscicide Cloethocarb (BASF, FRG) (slugs) showed no differences compared to the respective control group. PMID- 1616319 TI - Induction of hepatic CYP1A activity as a biomarker for environmental exposure to Aroclor 1254 in feral rodents. AB - Specimens of the feral mouse species Reithrodontomys fulvescens trapped from a polychlorinated biphenyl (PCB)-contaminated field location had hepatic ethoxyresorufin (ETR) O-dealkylase activities and immunoreactive CYP1A protein contents which were two- to threefold higher than those measured in animals of the same species and sex collected from non PCB-contaminated reference sites. Specimens with hepatic ETR O-dealkylase activities differing by as little as 50% could readily be assigned as originating from the PCB or reference sites by the use of a specific chemical inhibitor of cytochrome P450IA (CYP1A). The relative levels of ETR O-dealkylase activity in R. fulvescens significantly correlated with hepatic PCB burdens (r = 0.819, P less than 0.01). When the magnitudes of the induced ETR O-dealkylase activities corresponding to given hepatic PCB burdens were compared between the feral animals, F344/NCr rats (Rattus norvegicus) or B6C3F1 mice (Mus musculus) exposed in the laboratory to dietary Aroclor 1254, the order of sensitivity to the inducing effects of PCBs were F344/NCr rat greater than B6C3F1 mouse greater than R. fulvescens. PMID- 1616320 TI - Effect of subacute benzene exposure on the activity of two neuropeptide-degrading enzymes in the rat brain. AB - Benzene (Bz) is an important industrial chemical, a petroleum by-product, a component of unleaded gas, and thus a ubiquitous environmental pollutant. It is well established that this organic solvent possesses neurotoxic and behavioral effects. However, the neurochemical mechanism of the solvent action remains obscure. The aminopeptidases (AP) are proteolytic enzymes that have been proposed as a candidate regulator of the degradation of several neuropeptides. In this work, changes in Lys- and Leu-aminopeptidase activities in several rat brain regions after benzene administration are described. The AP activity was determined by measuring the rate of hydrolysis of the artificial substrates Lys- and Leu-2-naphthylamides (fluorimetrically detected in triplicate). Both enzyme activities decrease in the thalamus, hypothalamus, hippocampus, and amygdala after Bz treatment. It is suggested that these aminopeptidase activities play a part in the benzene action mechanism, possibly by regulating the activity of several neuroactive peptides. PMID- 1616321 TI - Rheumatoid arthritis in twins: a study of aetiopathogenesis based on the Australian Twin Registry. AB - The 1980 cohort of the Australian Twin Registry contains 3808 pairs of twins, 258 of whom self reported a diagnosis of rheumatoid arthritis (RA) in one or both subjects. Seventy two pairs were lost to follow up by 1990. The remaining 186 pairs received a self administered questionnaire, followed, if necessary, by telephone interviews to them, their general practitioners, and their specialists. Twenty discordant and three concordant pairs of twins were verified as having RA. The prevalence of RA in this sample was 0.40%. There was an 89% false positive rate for the self reported diagnosis of RA. Pairwise concordance percentages for RA were as follows: monozygotic 21% (95% confidence interval (CI) = 6 to 44), dizygotic 0% (95% CI = 0 to 25). It was concluded that: (a) there is a high false positive rate in self reporting RA; (b) the prevalence of RA in Australia may be less than the 0.8-1.0% often quoted; and (c) genetic factors play some part in the aetiopathogenesis of RA but do not account entirely for its determination. PMID- 1616322 TI - Controlled trial of methotrexate versus 10-deazaaminopterin in the treatment of rheumatoid arthritis. AB - A 15 week double blind controlled trial of methotrexate and 10-deazaaminopterin for the treatment of rheumatoid arthritis (RA) was performed in 26 patients. Significant improvement in all measured clinical parameters was observed in the two patient groups. The drugs were well tolerated; only one patient (10 deazaaminopterin) withdrew from the study because of side effects. It is concluded that, in the context of this relatively short clinical trial, 10 deazaaminopterin is at least as beneficial as methotrexate in the treatment of RA. PMID- 1616323 TI - Increased incidence of urinary tract infection in patients with rheumatoid arthritis and secondary Sjogren's syndrome. AB - The incidence of lower urinary tract infection in 120 women with rheumatoid arthritis and secondary Sjogren's syndrome was evaluated retrospectively. Thirty one patients (26%) had secondary Sjogren's syndrome. Recurrent urinary tract infection was significantly more common in these patients (11/31) than in patients without Sjogren's syndrome (4/89). Habitual leucocyturia was also more common in patients with secondary Sjogren's syndrome (18/31) than in patients with rheumatoid arthritis without Sjogren's syndrome (8/89). Of seven patients with vaginal sicca symptoms, six had recurrent urinary tract infection. Urinary 24 hour mucopolysaccharide excretion in 20 patients with Sjogren's syndrome was similar to the excretion in 10 patients without Sjogren's syndrome. These results show that recurrent urinary tract infection is significantly more common in women with rheumatoid arthritis and secondary Sjogren's syndrome. A local deficit in protective urinary mucosal secretion or other immune mechanisms may be responsible for this susceptibility. PMID- 1616324 TI - Sjogren's syndrome: a stepwise approach to the use of diagnostic tests. AB - One hundred and forty two patients (62 with definite Sjogren's syndrome, 24 with probable Sjogren's syndrome, and 56 in whom Sjogren's syndrome was finally ruled out) were studied. Schirmer's test and rose bengal staining for the diagnosis of keratoconjunctivitis sicca and salivary scintigraphy and a labial biopsy sample for the diagnosis of xerostomaia were studied in all patients. Rose bengal staining showed high specificity (98%) but low sensitivity (55%). All patients with positive rose bengal staining results had associated xerostomia. In the rose bengal staining positive patients, scintigraphy had 100% specificity. A labial biopsy sample showed high sensitivity in the rose bengal staining, salivary scintigraphy positive group, and high specificity in the rose bengal staining positive, salivary scintigraphy negative group. In patients with negative rose bengal staining, salivary scintigraphy showed 96% specificity and 36% sensitivity. A labial biopsy sample had a sensitivity and specificity greater than 90% in rose bengal staining negative patients. Only 29 biopsy samples were needed to achieve a diagnosis of Sjogren's syndrome in 142 patients (20%). Hence the suggested approach may make it unnecessary to take biopsy samples in approximately 80% of patients with suspected Sjogren's syndrome. Using the stepwise approach of first rose bengal staining, then salivary scintigraphy, and eventually a labial biopsy sample in patients with suspected Sjogren's syndrome, the diagnosis is relatively simple. PMID- 1616325 TI - Diversity and pattern of inheritance of autoantibodies in families with multiple cases of systemic lupus erythematosus. AB - The pattern of inheritance of autoantibodies in eight families chosen from a pool of 110 families of patients with systemic lupus erythematosus (SLE) is described. In all the eight families at least two members were already affected by SLE. In total, 19 patients and 43 first degree relatives were examined. The inheritance of a large set of antinuclear antibodies (for example, DNA, Sm, RNP, Ro, La, histones) and 16/6 idiotype seemed to be related to some unknown genetic factors but not related to HLA. The presence of numerous antinuclear autoantibodies in the serum of a subject was not necessarily associated with overt disease. The incidence of the 16/6 idiotype among patients and their relatives was low. It is not yet clear whether the 'autoantibody burden' is greater in families with multiple cases of SLE than in families with single cases. PMID- 1616326 TI - Risk factors in the pregnancy of patients with systemic lupus erythematosus: association of hypocomplementaemia with poor prognosis. AB - Fetal wastage is still high in the pregnancies of patients with systemic lupus erythematosus (SLE). We examined retrospectively the cases of 38 patients with inactive SLE in whom pregnancy was either desired or had already been obtained. The prevalence of antiphospholipid antibodies in the group with fetal loss was high. The antibodies were, however, also detected in five of 14 patients who had had a live birth. It was noted that low levels of serum complement activity (CH50 less than 25 U/ml) occurred in five of six patients with fetal loss, but in only two of 22 with a live birth. Serial studies also confirmed a close association between decreased serum complement activity and poor fetal prognosis in lupus pregnancy. Treatment with increased doses of prednisolone may help to achieve successful live births. Thus hypocomplementaemia may be associated with a worse prognosis for the fetus in the pregnancies of some patients with SLE in remission. PMID- 1616327 TI - Outcome of patients with systemic rheumatic disease admitted to medical intensive care units. AB - The outcome of patients admitted to intensive care units is known to be influenced by such factors as age, previous health status, severity of disease, and diagnosis. To estimate the outcome of such patients with systemic rheumatic diseases and to determine if the severity of these diseases unfavourably influences the prognosis at the time of admission to a medical intensive care unit, the clinical courses of all patients with systemic rheumatic disease admitted to two medical intensive care units between January 1978 and December 1988 were studied retrospectively. Sixty nine patients with systemic lupus erythematosus (n = 16), necrotising vasculitis (n = 19), rheumatoid arthritis (n = 19), and other systemic rheumatic diseases (n = 15) were included. The mean (SD) age on admission into the medical intensive care unit was 53 (17) years and the mean simplified acute physiological score was 12 (5.5). The principal diagnoses on admission were infectious complications (29/69 patients) and acute exacerbation of the systemic rheumatic disease (19/69 patients). The death rate in the medical intensive care unit was 33% (23/69 patients) and was similar to that of a non-selected population with comparable simplified acute physiological score. The death rate in hospital was 42% (29/69 patients). Infection was the main cause of death in the medical intensive care unit (19/23 patients) and the infection was mainly acquired in the unit. Only the simplified acute physiological score on admission was a statistically significant prognostic factor: the simplified acute physiological score in patients who died was 15 (5.2) v 9.9 (4.7) for survivors. Long term outcome analysis showed that 83% (33/40 patients) of patients were still alive after admission to the medical intensive care unit with a follow up time between two months and nine years (mean 38 months). The death rate was relatively high and was mainly due to nosocomial infections. It was not different, however, from that of nonselected patients and the long term prognosis was highly favourable. This shows that the complications are often reversible, particularly infectious applications, and justifies admission to the medical intensive care unit of this group of patients. PMID- 1616328 TI - Inhibition by prostaglandin E1 and E2 of 1,25-dihydroxyvitamin D3 synthesis by synovial fluid macrophages from arthritic joints. AB - Previous work has shown that renal metabolism of 25-dihydroxyvitamin D3 (25(OH)D3) to the active metabolite, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is stimulated by prostaglandin E2 and inhibited by acetylsalicylate (aspirin). As prostaglandins are primary inflammatory mediators and synovial fluid macrophages are known to synthesise 1,25(OH)2D3 in vitro, the effects of prostaglandin E1, prostaglandin E2, and aspirin on the metabolism of 25(OH)D3 by cells cultured from synovial fluid of patients with inflammatory arthritis were investigated. Most cultures contained non-proliferating macrophages which formed 1,25(OH)2D3; however, two of 13 cultures contained colonies of rapidly proliferating fibroblast-like cells which formed 24,25(OH)2D3 (24,25(OH)2D3). Prostaglandin E1 and prostaglandin E2 (0.01-10 mumol/l) induced marked inhibition of 1,25(OH)2D3 synthesis (up to 94%) in a dose dependent manner after preincubations of 24 hours but not over straightforward six hour incubations. Exposure of macrophages to aspirin (1 mumol/l-1 mmol/l) for 24 hours did not affect 1,25(OH)2D3 synthesis unless the cells had been pretreated with lipopolysaccharides, in which instance 1 mM aspirin increased 1,25(OH)2D3 synthesis. Lipopolysaccharide is a macrophage activating factor which stimulates macrophages to form 1,25(OH)2D3, and it also induces prostaglandin synthesis which would be inhibited by aspirin. Taken together these results suggest that prostaglandin E1 and prostaglandin E2 synthesised by macrophages may act in an autocrine manner to attenuate the ability of macrophage activating factors, such as lipopolysaccharide, to stimulate 1,25(OH)2D3 synthesis. Prostaglandins synthesised by other inflammatory cells may also inhibit 1,25(OH)2D3 synthesis in a paracrine manner. In contrast, prostaglandin E2 and aspirin had limited effects on fibroblast 24,25(OH)2D3 synthesis. This study shows that the effects of prostaglandin E1, prostaglandin E2, and aspirin in macrophages contrast with those previously reported for the renal 25(OH)D3-1alpha-hydroxylase, where prostaglandin E2 stimulated and aspirin inhibited enzyme activity. These results further emphasise that synthesis of 1,25(OH)2D3 in non-renal sites is independently regulated, which is consistent with it having an immunological role at a local level rather than playing a part in systemic calcium homeostasis. PMID- 1616329 TI - Interleukin 1 alpha and beta production by cells isolated from membranes around aseptically loose total joint replacements. AB - Aseptic loosening of joint prostheses is accompanied by local osteolysis. To determine whether local production of interleukin 1 might contribute to such lysis, the number of interleukin 1 secreting cells in the pseudosynovial membrane surrounding prostheses was measured. Interleukin 1 alpha and beta secreting cells were identified by ELISPOT, a sensitive cytokine secreting assay. The proportion of interleukin 1 beta secreting cells in pseudosynovial membrane was comparable with the proportion occurring in the synovium of patients with rheumatoid arthritis and higher than that in normal subjects and patients with osteoarthritis. The proportion of interleukin 1 alpha producing cells was higher in pseudosynovial membrane than in diseased synovium. Overall, higher numbers of interleukin 1 beta than interleukin 1 alpha secreting cells were detected. A correlation was observed between the number of cells in pseudosynovial membrane producing interleukin 1 beta and those producing interleukin 1 alpha. When divided into area of origin, tissue samples from the femoral area contained a higher proportion of interleukin 1 beta producing cells than tissue in the acetabular or capsular regions, though due to variance within each group this difference did not reach significance. PMID- 1616330 TI - Inhibition of proteoglycan synthesis by transforming growth factor beta in anatomically intact articular cartilage of murine patellae. AB - The effect of transforming growth factor beta (TGF beta) on proteoglycan synthesis and degradation in anatomically intact articular cartilage of murine patellae was studied. Exogenously added TGF beta up to a concentration of 200 pmol/l had no effect on proteoglycan synthesis in intact articular cartilage. Neutralisation of endogenously produced TGF beta with a specific monoclonal antibody to TGF beta, however, led to stimulation of proteoglycan synthesis, indicating that TGF beta itself inhibits proteoglycan synthesis in anatomically intact cartilage. Transforming growth factor beta decreased the degradation of proteoglycans in intact cartilage in the absence of fetal calf serum or insulin like growth factor 1. In the presence of fetal calf serum or insulin-like growth factor 1, TGF beta had no additional effect on proteoglycan breakdown. PMID- 1616332 TI - Echocardiographic abnormalities in ankylosing spondylitis. AB - Twenty four patients with ankylosing spondylitis of 10 or more years' duration were assessed for evidence of cardiac disease. Seven patients (29%) had evidence of cardiac disease, including one patient with a pericardial effusion, three with conduction abnormalities, and two with aortic incompetence. Aortic incompetence in one patient was clinically silent and was detected only with Doppler echocardiography. This patient had, in addition, thickening of the posterior aortic wall, an echocardiographic feature not previously described in ankylosing spondylitis. There was no evidence of aortic valve disease in a control group matched for age and sex. Patients with ankylosing spondylitis and cardiac abnormalities were older, had a longer disease duration, and more peripheral joint disease than those without cardiac abnormalities. Doppler echocardiography is a useful technique in the assessment of cardiac disease in ankylosing spondylitis and may detect aortic valve disease at an early preclinical stage. PMID- 1616331 TI - Urinary excretion of pyridinium crosslinks of collagen in patients with osteoporosis and the effects of bone fracture. AB - Values for the urinary excretion of pyridinium crosslinks of collagen, pyridinoline and deoxypyridinoline, in a group of 30 elderly women with femoral fractures associated with osteoporosis and a group of 20 women without recent fracture but with overt or suspected osteoporosis were compared with 27 control subjects matched for age. Relative to the control group, the excretion of the crosslinks was significantly higher in the group with fractures and the group with osteoporosis. Fractures contributed markedly to the excretion of pyridinium crosslinks as the patients with fractures showed significantly higher excretion of pyridinoline and deoxypyridinoline than the group without recent fractures. This was confirmed by the fact that excretion of pyridinium crosslinks in patients with accidental bone fractures was significantly higher than for healthy control subjects matched for age and sex. The crosslinks appear to provide valid indices of bone resorption, but the effects of bone fracture must be considered in the clinical application of this technique. PMID- 1616333 TI - Chronic otitis media: a new extra-articular manifestation in ankylosing spondylitis? AB - Following a study reporting a fourfold increase in the occurrence of chronic otitis media in patients with ankylosing spondylitis, this prospective study examines this association with respect to severity, duration of disease, and acute phase in ankylosing spondylitis. Forty two consecutive patients with classical ankylosing spondylitis seen at the rheumatology clinic of a teaching hospital where the features of ankylosing spondylitis were recorded had an otological examination by an otolaryngologist. The occurrence of chronic otitis media (all categories) was 12/42 (29%). The acute phase serum markers (C reactive protein and IgG) were increased in patients with active or inactive chronic otitis media. Extra-articular manifestations were significantly more common in the chronic otitis media group than in those with no history of chronic otitis media. The results of this study suggest that chronic otitis media may be another extra-articular manifestation of ankylosing spondylitis. Alternative explanations, however, include similar aetiological factors for the two conditions or a previously unrecognised increased occurrence of HLA-B27 in patients with chronic otitis media. PMID- 1616334 TI - Sternocostoclavicular hyperostosis: its progression and radiological features. A study of 12 cases. AB - Twelve cases of sternocostoclavicular hyperostosis were followed up over four to 16 years. The patients underwent repeated radiological examinations of the sternocostoclavicular joints and the sternum, and the extrasternal osseous manifestations of the disease were studied to show changes in the radiological features during long term follow up. Five of 12 (41%) patients had extrasternal manifestations. With the exception of one patient extrasternal manifestations were first detected by scintigraphs because they were asymptomatic. With respect to the sternal manifestations the initial radiological diagnosis was made during an acute phase while painful swelling over the sternum and decreased mobility of the shoulders occurred. The radiological examinations showed the signs of a proliferative destructive arthritis in most patients. In contrast with the frequent occurrences of clinical symptoms, the radiological signs of progression take several years to become detectable. There are no specific bacteriological, serological or histological findings. Usually a permanent increase in the erythrocyte sedimentation rates is found. Sternocostoclavicular hyperostosis is a slowly progressing disease, characterised by a chronic aseptic destructive sternoclavicular arthritis with a reactive low turnover sclerosis that begins in a similar way to an enthesopathy and ends after several decades with total ankylosis. The radiological identification of retrosternal proliferation of soft tissue by computed tomography was found to be a valuable criterion for the differential diagnosis from other benign hyperostotic processes of the sternoclavicular region. PMID- 1616335 TI - Role of technetium-99m diphosphonate and gallium-67 citrate bone scanning in the early diagnosis of infectious spondylodiscitis. A comparative study. AB - A comparative study of the parts played by technetium-99m diphosphonate and gallium-67 citrate bone scanning in the early diagnosis of infectious spondylodiscitis is presented. Nineteen patients were included in the study. All patients (11 men aged 19-70 years and eight women aged 18-72 years) had a history of back pain varying in duration from one to 15 weeks. A 99mTc diphosphonate bone scan was positive in 17 patients. The two patients with negative results had less than two weeks of back pain. The 67Ga citrate bone scan showed uptake in all patients. PMID- 1616336 TI - Heredofamilial deficiency of monocyte esterase in patients with rheumatoid arthritis. AB - Deficiency of the monocyte ectoenzyme non-specific esterase is described in a heredofamilial pattern in four patients with rheumatoid arthritis. No association with HLA status or rheumatoid factor seropositivity was found. PMID- 1616337 TI - Antiphospholipid antibodies in homozygous sickle cell disease. AB - Serum samples from 108 unselected Jamaican patients with homozygous sickle cell disease and 116 control subjects with normal haemoglobin were screened for the presence of antiphospholipid antibodies. Slightly increased levels of IgG antiphospholipid antibodies were found in nine patients with sickle cell disease and in none of the control subjects. Serial control samples confirmed the increased levels of antiphospholipid antibodies. A comparison of the haematological and clinical features of patients with positive and negative antiphospholipid sickle cell disease did not highlight any differences between the groups. PMID- 1616338 TI - HTLV-I associated arthritis: characteristics of an HTLV-I virus infected T cell line from synovial fluid. AB - A T cell line from mononuclear cells in the synovial fluid of a patient with polyarthritis was established. The T cell line reacted with serum samples positive for antibodies to human T cell lymphotropic virus type I (HTLV-I) and with monoclonal antibody to HTLV-I p19. In Southern blotting with an env-pX-LTR HTLV-I probe and digestion of T cell line DNA with the restriction enzymes ClaI, DraI, and PstI generated fragments that were identical to those found in two HTLV I infected T cell lines established from adult T cell leukaemia or HTLV-I associated myelopathy. The T cell line expressed CD2, CD3, CD4, CD45RA, CD29, HLA DR, CD25, and CD26 antigens, but not CD8 and CD20 antigens. Large amounts of interleukin 6, interferon gamma, and tumour necrosis factor alpha were secreted in the culture supernatants of this cell line. This line helped immunoglobulin production by B cells, but not K562, Raji, and synovial cell lysis. PMID- 1616339 TI - Polyarteritis associated with Yersinia enterocolitica infection. AB - A patient developed polyarteritis, predominantly affecting the muscles, 10 days after a Yersinia enterocolitica O:3 infection. Immunoperoxidase staining showed Yersinia enterocolitica O:3 antigen in the subendothelial layer of the blood vessels. This suggests that vasculitis should be considered as a rare manifestation of Yersinia enterocolitica infection. PMID- 1616341 TI - Evaluation of serum ferritin as a marker for adult Still's disease activity. AB - Extremely high serum ferritin values (greater than 10,000 micrograms/l) were detected in two patients with adult Still's disease. The ferritin concentrations decreased to normal after adequate treatment. During a one year follow up ferritin concentration was helpful in monitoring disease activity and guiding decisions about treatment. Raised concentrations of soluble interleukin 2 receptors (sCD25) were also found. Detection of ferritin values above 3000 micrograms/l should lead to the consideration of Still's disease when there is an acute febrile illness without evidence for bacterial or viral infections, serum ferritin being suitable for monitoring treatment. PMID- 1616340 TI - Monarthritis: an unusual presentation of renal cell carcinoma. AB - Two cases of acute monarthritis secondary to asymptomatic renal cell carcinoma are described. This association has not previously been reported. The patients were initially thought to have a septic arthritis, but hot spots were seen on isotope bone scans and biopsy samples showed secondary neoplasms, which were later confirmed to be a result of renal cell carcinomas. The value of cytological examination of synovial fluid when there is clinical doubt as to the cause of a joint effusion is shown. PMID- 1616342 TI - Acute aortic insufficiency in a patient with presumed Reiter's syndrome. AB - Cardiac disease is rare in patients with Reiter's syndrome. There have been 15 reported cases of aortic insufficiency in patients with Reiter's syndrome, with the aortic insufficiency developing over several years. This paper reports the case of a black HLA-B27 negative woman who presented with Reiter's syndrome and acute aortic insufficiency. An antecedent streptococcal infection is suggested as the inciting factor. To our knowledge, this is the first report of Reiter's syndrome in a black woman with acute aortic insufficiency. PMID- 1616343 TI - An infiltrating rheumatoid nodule? AB - The case is presented of a patient with mild rheumatoid arthritis who developed an enlarged painful tissue mass in the left lower leg. Although the history, clinical, and imaging appearances suggested that it was a soft tissue sarcoma, a biopsy specimen showed histological features consistent with either a rheumatoid nodule or subcutaneous granuloma annulare. PMID- 1616344 TI - Fungal arthritis. PMID- 1616346 TI - From Britain, 1991. PMID- 1616345 TI - Local immune responses in certain extra-articular manifestations of rheumatoid arthritis. PMID- 1616347 TI - Septic arthritis complicating hip osteoarthritis. PMID- 1616348 TI - Symptomatic salicylate ototoxicity: a useful indicator of serum salicylate concentration? PMID- 1616349 TI - The heart in ankylosing spondylitis. PMID- 1616350 TI - Inhibition of astrocyte proliferation and binding to brain tissue of anticardiolipin antibodies purified from lupus serum. AB - Polyclonal anticardiolipin antibodies purified from pooled serum samples of patients with systemic lupus erythematosus were shown to have inhibitory effects on cultured normal rat brain astrocytes (RBA-1 cells). Anticardiolipin antibodies at concentrations from 50 to 200 micrograms/ml inhibited the [3H]thymidine incorporation of RBA-1 cells in a dose dependent manner after three days of culture. A kinetic study showed that anticardiolipin antibodies (100 micrograms/ml) maximally inhibit the proliferation of RBA-1 cells (20.6 (5.1)% of the control value) after incubation for one day. In contrast, human gamma globulin (100 micrograms/ml) had no effect on these cells. In the presence of anticardiolipin antibodies (100 micrograms/ml), the RBA-1 cells attached to the bottom of wells became spherical and the expression of glial fibrillary acidic protein in the cytoplasm was slightly reduced. Using 3,3'-dihexyloxacarbocyanine iodide as an indicator, anticardiolipin antibodies depolarised the membrane potential of RBA-1 cells after one day of culture. In addition, the percentage binding of RBA-1 cells with anticardiolipin antibodies was greater than with gamma globulin as determined by flow cytometric analysis. Immunofluorescence staining of brain tissue from BALB/c mice with anticardiolipin antibodies was noted in the corpus callosum, the cellular zone near the corpus callosum, and cells scattered in brain tissue. These results suggest that anticardiolipin antibodies have an inhibitory effect on brain cells and elicit thrombus formation in brain vessels, which plays a part in neuropsychiatric lupus. PMID- 1616351 TI - Autoantibodies to T and B cell lines detected in serum samples from patients with systemic lupus erythematosus with lymphopenia and hypocomplementaemia. AB - Antibodies to lymphocytes in serum samples from 88 patients with systemic lupus erythematosus (SLE) and 15 normal control subjects were examined by a cell enzyme linked immunosorbent assay (ELISA) with four human T and B cell lines as antigens. The antibodies reacted with the Wa B cell line and the T cell lines P12 (CD4-, CD8+), Jurkat (CD4-, CD8-), and Hut78 (CD4+, CD8-). Antibody titres in serum samples from patients with SLE were higher than in those from normal control subjects. Titres of antibodies to P12 were correlated with titres of antibodies to Wa, Jurkat, and Hut78 in serum samples from patients with SLE. IgG antibodies to P12 were associated with lymphopenia and reduced haemolytic complement. By thin layer chromatography immunostaining, the antibodies in serum samples from two of 10 patients with SLE with high titres of IgG antibodies to P12 and lymphopenia were shown to react with three monosialoglycosphingolipids and two neutral glycosphingolipids from P12 cells. Antibodies to lymphocytes in serum samples from patients with SLE react with T and B cell lines, recognise a series of cell membrane glycosphingolipids and are associated with the lymphopenia and hypocomplementaemia typical of active disease. PMID- 1616352 TI - Rash in systemic lupus erythematosus: prevalence and relation to cutaneous and non-cutaneous disease manifestations. AB - Rash is a common cutaneous sign in patients with systemic lupus erythematosus (SLE) but no data regarding its prevalence or relation to disease manifestations are known, possibly due to the fact that it is a common but non-specific sign. Rash was present in 48/81 (59%) patients with SLE. Patients with rash had more cutaneous symptoms and signs, lymphadenopathy, increased levels of antibodies to double stranded DNA and decreased complement levels. They were also receiving a higher dose of prednisone. There was no difference between patients with and without rash with respect to renal or central nervous system disease. Rash did not correlate with the disease activity index and clinical parameters of disease exacerbation. PMID- 1616353 TI - Immunofluorescence microscopy of healthy skin from patients with systemic lupus erythematosus: more than just the lupus band. AB - Many papers have been published on the lupus band in systemic lupus erythematosus (SLE), but little information exists on the possible diagnostic value of the lupus band and other microscopic immunofluorescence phenomena found in clinically normal skin of patients with SLE. In a study of 297 subjects (66 patients with SLE, 81 patients with other forms of LE, and 150 patients with other systemic connective tissue disorders) it was found that: (a) granular deposits of IgA, IgG, and IgM in the basal membrane zone and in the deeper blood vessels were more common in patients with SLE than in the other two groups; (b) depending on the clinical differential diagnosis, IgA and IgG deposits at the epidermal basal membrane can be specific for SLE; (c) using logistic regression analysis sets of variables can be selected with a high potential to discriminate between SLE and the other groups; and (d) immunofluorescence variables do not duplicate the information for the diagnosis of SLE given by the American Rheumatism Association (ARA) criteria or other laboratory methods. From these results, it is concluded that immunofluorescence microscopy of clinically normal skin is a valuable diagnostic method which should be reconsidered as a potential criterion for the diagnosis of SLE in the next evaluation of the ARA criteria. PMID- 1616354 TI - Effects of ultraviolet irradiation on natural killer cell function in systemic lupus erythematosus. AB - In vitro irradiation with long wavelength ultraviolet light (UV-A), in clinically relevant dosages, of a natural killer cell line containing cell preparations from 17 control subjects reduced natural killer cell cytotoxicity with the cell line K562 as target. The spontaneous function of natural killer cells from 12 patients with systemic lupus erythematosus (SLE) correlated inversely with the one hour erythrocyte sedimentation rate, but not with glucocorticoid doses. After UV-A exposure, natural killer cells from patients with SLE exert either increased or decreased cytotoxicity, and the direction of change is inversely correlated with the spontaneous natural killer cell function. PMID- 1616355 TI - Determination of cytokines in synovial fluids: correlation with diagnosis and histomorphological characteristics of synovial tissue. AB - In a study aimed at correlating cytokine levels in synovial fluid with the pathology of rheumatoid arthritis (RA), tumour necrosis factor alpha, interleukin 1 beta and interferon gamma were immunoassayed in 27 patients with RA, 16 patients with other arthritides, 23 with osteoarthritis, 13 patients with trauma, and 18 patients at necropsy without inflammatory disease and not known to have had joint disease (median 27 hours after death). The results for interleukin 1 beta clearly show higher cytokine levels in patients with RA and other arthritides than in patients with osteoarthritis, trauma, or the patients at necropsy. Interferon gamma levels in patients with osteoarthritis and the patients at necropsy, however, were significantly greater than in patients with RA, and tumour necrosis factor alpha levels were also greater in the patients at necropsy compared with patients with RA. This study also correlated histomorphological patterns of synovitis and indicators of local inflammatory activity with synovial fluid cytokine levels, showing, for example, a positive association of interleukin 1 beta titre and a negative association of interferon gamma titre with ulcerogranulomatous synovitis (itself associated with RA). Taken together, these results extend and strengthen data suggesting a possible part played by increased synovial fluid levels of interleukin 1 beta in joint destruction in RA, but provide no evidence for increases in levels of tumour necrosis factor alpha or interferon gamma affecting the disease pathology. PMID- 1616356 TI - Localisation of fibronectin mRNA in the rheumatoid synovium by in situ hybridisation. AB - The distribution of fibronectin, an extracellular matrix glycoprotein which plays a part in fibrosis and tissue repair, has previously been described using immunohistochemical methods. These do not differentiate between locally synthesised and plasma derived fibronectin. In this work the distribution of cells actively synthesising fibronectin was assessed by in situ hybridisation using a radiolabelled antisense RNA probe in synovial biopsy samples from patients with rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and control subjects without inflammatory disease. Large amounts of fibronectin mRNA were found specifically in synovial lining cells, providing evidence for the local production of fibronectin in the synovium. Levels of fibronectin mRNA were variable between patients. These differences were not related to the diagnosis or to the subintimal inflammatory cell infiltrate; where there was synovial lining cell hyperplasia there was a concomitant increase in the number of cells containing fibronectin mRNA, which was consistent with increased levels of immunoreactive fibronectin at this site. Increased levels of fibronectin in synovial fluid in patients with rheumatoid arthritis may be due to an increased number of lining cells secreting the protein, rather than upregulation of the gene by these cells. PMID- 1616357 TI - Response of anaemia in rheumatoid arthritis to treatment with subcutaneous recombinant human erythropoietin. AB - Eleven patients with chronic inflammatory arthritides and haemoglobin concentrations less than 105 g/l with symptoms from their anaemia were treated with a dose of 250 IU/kg/week of recombinant human erythropoietin for six weeks. The treatment was given as subcutaneous injections five days a week. All patients had active inflammatory disease. Nine patients responded to treatment with an increase in haemoglobin of more than 15 g/l. The mean (SD) haemoglobin concentration increased from 93.0 (8.0) g/l before treatment to 115.0 (12.0) g/l after six weeks. There was no correlation between the initial serum concentration of erythropoietin and the response. It was concluded that anaemia in chronic inflammatory arthritides responds to treatment with subcutaneous injections of recombinant human erythropoietin. PMID- 1616358 TI - Anaemia of chronic disease in rheumatoid arthritis: effect of the blunted response to erythropoietin and of interleukin 1 production by marrow macrophages. AB - Anaemia in rheumatoid arthritis (RA) is a common and debilitating complication. The most common causes of this anaemia are iron deficiency and anaemia of chronic disease. Investigations have suggested that interleukin 1 (IL-1) or tumour necrosis factor (TNF), or both, from monocytes associated with chronic inflammation are responsible for the anaemia of chronic disease. On bone marrow examination anaemia of chronic disease is characterised by the diversion of iron from the erythropoietic compartment into marrow macrophages. This phenomenon is termed failure of iron utilisation. In this study, CFU-E (colony forming unit erythroid; late red cell precursors) and BFU-E (burst forming unit erythroid; early red cell precursors) stem cells were cultured from 10 normal marrow samples and 12 marrow samples from patients with RA with iron deficiency anaemia and 10 samples from patients with RA with failure of iron utilisation. All patients with RA were anaemic (haemoglobin less than 100 g/l), Potential accessory or inhibitory cells of erythropoiesis (CD4, CD8, or CD14 positive cells) were removed before culture. Control marrow samples were studied in a similar manner. Normal marrow samples yielded 377 (17) CFU-E and 133 (6) BFU-E (mean (SD)) colonies for each 2 x 10(5) light density cells plated. CD4 ablation caused reductions of 62 and 100% in CFU-E and BFU-E colonies respectively. CD14 removal resulted in considerable but lesser reductions of 46% for CFU-E and 25% for BFU E. In both groups of patients with RA, CFU-E colony numbers were significantly lower than those seen in normal control subjects, 293 (17) for patients with iron deficiency anaemia and 242 (35) for patients with failure of iron utilisation. BFU-E colony numbers were 102 (13) and 108 (20) respectively. In patients with RA, CD4 removal caused a significantly greater loss of CFU-E colonies compared with normal control subjects. Cytolysis of CD14 positive cells caused a reduction in CFU-E colonies in the two RA groups which was similar to that seen in normal subjects. In conclusion, patients with RA seem to have fewer CFU-E progenitors but essentially normal numbers of BFU-E stem cells. Our data suggest a stimulatory role for marrow CD4 and CD14 cells in erythropoiesis in patients with RA. Monocytes-macrophages (CD14 positive) are known to be producers of IL-1 or TNF, or both, however, the predicted increase in the CFU-E colonies on removal of CD14 cells is not seen. Therefore, if IL-1 or TNF, or both, are responsible for the impairment of erythropoiesis in patients with RA, marrow macrophages are unlikely to be the source. Moreover, these results indicate the probability of erythropoietin resistance on the basis of diminished CFU-E colony formation in patients with RA. PMID- 1616359 TI - Double blind, placebo controlled study of metronidazole as a disease modifying agent in the treatment of rheumatoid arthritis. AB - Anecdotal reports suggest that metronidazole may have disease modifying activity in the treatment of rheumatoid arthritis. To assess possible beneficial effects a double blind, comparative trial of metronidazole and placebo was performed. Fifty patients with active rheumatoid arthritis were randomly allocated to receive active drug (n = 24) or placebo (n = 26) and reviewed at weeks 0, 1, 4, 8, 12, 16, and 24. Detailed assessment of drug safety, biochemical and haematological parameters, and efficacy was made at these dates. Dose regimen was 400 mg twice daily from weeks 0 to eight, increasing to 400 mg three times a day from weeks nine to 24 provided that no adverse effects were recorded. Most patients were unable to tolerate metronidazole because of side effects or lack of efficacy, with only five (21%) continuing to take the drug at 24 weeks. For those patients attaining 12 weeks of treatment an overall improvement in articular index and morning stiffness was found. No improvement in laboratory indices of disease activity was seen, however. In this study metronidazole did not have disease modifying properties and was unacceptably toxic. PMID- 1616360 TI - Intranasal calcitonin for the prevention of bone erosion and bone loss in rheumatoid arthritis. AB - The effect of intranasal salmon calcitonin on pain, erosion progression, and bone loss in 40 women with rheumatoid arthritis was investigated. The study design was double blind, placebo controlled for the first four months and open for the next 36 months, allowing for cross over to active drug treatment or to the control group. Morning stiffness was reduced in the group treated with salmon calcitonin after two and four months. After an average follow up of 28 months no significant effect on erosion progression was observed using the Larsen score. The mean (SD) monthly progressions in the Larsen score in the calcitonin and control groups were 0.21 (0.22) and 0.23 (0.28) respectively. The bone mineral density was evaluated in the forearm and spine. During the 12 months of follow up the control group lost bone at a rate of 2%/year at the spine and 4.8%/year at the radius distal third. In contrast, the group receiving nasal calcitonin gained 1% in bone mineral density at the lumbar spine and no loss at the radius distal third. The increase in bone density at the spine in the calcitonin group was not sustained and a loss of 1.8%/year was observed in the second year. The difference with the placebo group remained significant. PMID- 1616361 TI - Opinions of patients with rheumatoid arthritis about their own functional capacity: how valid is it? AB - Self assessment health status questionnaires are increasingly used to measure health status or the effect of treatment in patients with rheumatoid arthritis (RA). Most of these questionnaires measure functional (physical) disabilities. The question arises, however, as to how well self assessment questionnaires reflect the true functional status of patients or whether they only reflect their imaginary functional capacities. How valid is the opinion of patients with RA about their own functional capacity? To answer this question an investigation was performed in 80 patients with RA. Forty Dutch and 40 Belgian patients with RA completed the functional items of the DUTCH-AIMS, the Dutch version of the Arthritis Impact Measurement Scales (AIMS), a self assessment questionnaire specific to arthritis. Their scores on the functional scales were compared with the scores on the same scales completed by two experienced physiotherapists after evaluation of the functional ability of these patients. This was achieved by observing the patients perform the tasks given in the questionnaire. Correlation coefficients between the scores of the patients and the physiotherapists were highly significant for all the scales. No significant differences were found between the patients' and physiotherapists' mean scale scores except for the mobility scale in the Dutch patients. The strength of agreement (Cohen's kappa) of most scale scores of the patients and physiotherapists was substantial. The estimates of the overall functional capacity (the mean of the five scale scores) of the Belgian and Dutch patients show high correlations between the patients and the physiotherapists. It is concluded that patients' opinion about their functional ability is valid in that it is in agreement with their real functional abilities. This study provides further evidence for the validity of the DUTCH AIMS as a measure of functional disability and health status in Dutch and Belgian patients with RA. PMID- 1616362 TI - Follow up study of labial salivary gland lesions in primary Sjogren's syndrome. AB - Labial salivary gland biopsy samples were taken from 27 patients with primary Sjogren's syndrome (SS), 10 with rheumatoid arthritis (RA) and secondary SS, and four normal control subjects on two occasions at intervals of more than one year. In the former group of patients, eight of the nine initially negative analyses were positive on the second sample, whereas two of the seven patients with RA and secondary SS were negative for the first sample and then positive for the second. In primary SS, the mean (SD) variation of the focus score was 1.7 (2.6) and that of salivary duct infiltration 0.2 (0.7). The former correlated well with the latter. PMID- 1616363 TI - Soluble interleukin 2 receptors in patients with polymyositis/dermatomyositis. AB - The concentration of soluble interleukin 2 receptor was determined in serum samples from 19 patients with polymyositis/dermatomyositis by an enzyme linked immunosorbent assay (ELISA). The concentration of soluble interleukin 2 receptor in serum samples from patients with polymyositis/dermatomyositis was higher than that in samples from normal subjects. PMID- 1616364 TI - Absence of autoantibodies to peptides shared by HLA-B27.5 and Klebsiella pneumoniae nitrogenase in serum samples from HLA-B27 positive patients with ankylosing spondylitis and Reiter's syndrome. AB - Some microorganisms which are pathogenic in humans share amino acid sequences with human proteins (molecular mimicry). It has been suggested that molecular mimicry might be a reason for autoimmunity as a result of immunological cross reactivity. A homologous sequence of six amino acids has been found in both Klebsiella pneumoniae nitrogenase and the HLA-B27.5 molecule. In addition, (auto)antibodies to a synthetic peptide that contained the HLA-B27.5/klebsiella mimicking epitope have been detected in serum samples from HLA-B27 positive patients with ankylosing spondylitis and Reiter's syndrome. Confirmation of these data is important, because ankylosing spondylitis and Reiter's syndrome have so far been assumed to be 'seronegative' rheumatic diseases. It was, however, not possible to confirm the presence of autoantibodies against the mimicking peptide in serum samples from patients with ankylosing spondylitis and Reiter's syndrome. Serum samples from 81 patients with ankylosing spondylitis, 38 patients with Reiter's syndrome, and 81 healthy blood donors were tested against the 'mimicking peptide' in an enzyme linked immunosorbent assay (ELISA). Some of the serum samples from patients showed high but non-specific binding to the mimicking peptide. A highly significant correlation between binding to plastic coated with the mimicking peptide, to plastic coated with an irrelevant peptide, and even to non-coated plastic was observed. The nature of the serum component(s) in these patient serum samples (and some control serum samples) responsible for the high non-specific binding to plastic remains unclear. It was also shown that antibodies to the HLA-B27 peptide (containing the mimicking epitope) induced in rabbits do not cross react with the klebsiella peptide and vice versa. PMID- 1616365 TI - Increased levels of serum IgA as IgA1 monomers in ankylosing spondylitis. AB - The various subsets of serum IgA were determined in 43 patients with ankylosing spondylitis to investigate the putative mucosal origin of increased IgA concentrations in this disease. Total IgA was shown to be increased and weakly correlated with the erythrocyte sedimentation rate (ESR). In contrast, although the mean concentration (but not the median) of secretory IgA (SIgA) was slightly increased, no correlation was found with total IgA nor the ESR. Moreover, molecular sieving of nine serum samples selected for their high concentrations of total IgA, and absorption with insoluble jacalin showed these immunoglobulins to be essentially monomers of the IgA1 subclass. These results are consistent with a non-secretory origin of the increase of serum IgA, which must be ascribed to the central immune system. PMID- 1616366 TI - Joint hypermobility in adults referred to rheumatology clinics. AB - Joint hypermobility is a rarely recognised aetiology for focal or diffuse musculoskeletal symptoms. To assess the occurrence and importance of joint hypermobility in adult patients referred to a rheumatologist, we prospectively evaluated 130 consecutive new patients for joint hypermobility. Twenty women (15%) had joint hypermobility at three or more locations (greater than or equal to 5 points on a 9 point scale). Most patients with joint hypermobility had common musculoskeletal problems as the reason for referral. Two patients referred with a diagnosis of rheumatoid arthritis were correctly reassigned a diagnosis of hypermobility syndrome. Three patients with systemic lupus erythematosus had diffuse joint hypermobility. There was a statistically significant association between diffuse joint hypermobility and osteoarthritis. Most patients (65%) had first degree family members with a history of joint hypermobility. These results show that joint hypermobility is common, familial, found in association with common rheumatic disorders, and statistically associated with osteoarthritis. The findings support the hypothesis that joint hypermobility predisposes to musculoskeletal disorders, especially osteoarthritis. PMID- 1616367 TI - Aberrant cytokine production from tenosynovium in dialysis associated amyloidosis. AB - Culture supernatants of tenosynovial tissues from patients with carpal tunnel syndrome undergoing chronic haemodialysis contained interleukin (IL) 1-like and IL6-like activity. These culture supernatants also induced active proliferation of rheumatoid synovial cells. Immunohistochemical analysis of teno-synovial tissues showed the accumulation of mononuclear cells bearing CD14 and HLA-DR antigens adjacent to the deposition of amyloid protein (beta 2 microglobulin). These cells also reacted with antibodies to IL1 and IL6 respectively. These data suggest that multiple cytokines, including IL1 and IL6, produced from tenosynovial tissues in patients with dialysis associated amyloidosis might induce the proliferation of synovial cells that, together with deposition of amyloid protein, might cause carpal tunnel syndrome. PMID- 1616368 TI - Possible induction of systemic lupus erythematosus by human parvovirus. AB - A 59 year old woman presented with an influenza-like illness preceding signs and symptoms strongly suggestive of systemic lupus erythematosus (SLE), which progressed over several months. Owing to these influenza-like symptoms, a viral cause of her illness was sought. Human parvovirus B19 serology was positive and antibodies to DNA were detected by two different methods. This patient is believed to be the first report of human parvovirus B19 infection coinciding with the onset of SLE. The evidence for B19 virus and the part it plays in autoimmunity and arthritis is discussed. PMID- 1616369 TI - Histiocytic necrotising lymphadenitis in systemic lupus erythematosus. AB - Histiocytic necrotising lymphadenitis is the pathognomonic histological appearance of lymph nodes in Kikuchi's disease, a condition characterised by a brief systemic illness and lymphadenopathy. The case is described of a young man, originally diagnosed as having Kikuchi's disease by lymph node histology, who subsequently developed systemic lupus erythematosus with symmetrical polyarthritis, Coombs' positive haemolytic anaemia and haemorrhagic pneumonitis. The case emphasises that a range of diseases is associated with histiocytic necrotising lymphadenitis, belying the unitary impression given by the term Kikuchi's disease. PMID- 1616370 TI - Primary Sjogren's syndrome preceding the presentation of systemic lupus erythematosus as a benign intracranial hypertension syndrome. AB - The case is reported of a 41 year old white woman who developed systemic lupus erythematosus (SLE) seven years after primary Sjogren's syndrome and four years after the association of Sjogren's syndrome with Jaccoud's arthritis. The SLE was detected by a benign intracranial hypertension, which is a rare neuro-ophthalmic presentation of lupus. No associated conditions linked to benign intracranial hypertension syndrome were seen in this patient and the hypertension syndrome recurred one year later. PMID- 1616371 TI - Knee contractures as the presenting manifestation of scleroderma. AB - Musculoskeletal disorders may be the primary manifestations of scleroderma. The case is reported of a patient admitted for an evaluation of severe knee flexion contractures who was diagnosed as having scleroderma but lacked the typical presenting features of the disease. Radiographic, serological, and histological support for this diagnosis are presented. Scleroderma should be considered in the diagnostic evaluation of joint contractures. PMID- 1616372 TI - Granulomatous lipophagic panniculitis and temporal arteritis in a patient with cryptogenic chronic active hepatitis. AB - An elderly woman receiving long term treatment with prednisone and azathioprine for cryptogenic chronic active hepatitis developed granulomatous lipophagic panniculitis and temporal arteritis. The lymphoplasmahistiocytic inflammatory reaction pattern is common to this patient's three diseases. It is suggested that an aberration of the defence mechanisms, immunological or otherwise, is responsible for this unusual occurrence. The triple association of chronic active hepatitis, granulomatous panniculitis and temporal arteritis has not been reported previously. PMID- 1616373 TI - Multicentric reticulohistiocytosis with arthritis and cardiac infiltration: regression following treatment for underlying malignancy. AB - The case is reported of a 63 year old man presenting with a rapidly destructive symmetrical polyarthritis and widespread papular nodular skin lesions, confirmed by a biopsy to be due to multicentric reticulohistiocytosis. Biventricular cardiac failure developed secondary to extensive myocardial infiltration with multicentric reticulohistiocytosis, a complication of this disease which has not previously been reported. The joint, skin, and cardiac manifestations of multicentric reticulohistiocytosis substantially regressed following resection of an associated squamous cell carcinoma. This report adds to the small amount of published work which suggests that multicentric reticulohistiocytosis can be a paraneoplastic disease that may respond to treatment directed at the underlying tumour. PMID- 1616374 TI - Bone mass in osteoarthritis. PMID- 1616375 TI - Bone mass in patients with rheumatoid arthritis. PMID- 1616376 TI - The genuine Southern surgeon. PMID- 1616377 TI - 103rd Annual Scientific Session of the Southern Surgical Association. Hot Springs, Virginia, December 1-4, 1991. PMID- 1616378 TI - Protecting the ischemic spinal cord during aortic clamping. The influence of anesthetics and hypothermia. AB - Infrarenal circumaortic occlusion devices were operatively placed in 74 New Zealand white rabbits. Two days after operation the animals were randomly assigned to one of seven treatment groups: I, control, n = 23; II, halothane, n = 8; III, thiopental, n = 12; IV, ketamine (30 mg/kg intravenously), n = 6; V, halothane+hypothermia, n = 8; VI, thiopental+hypothermia, n = 12; VII, ketamine+hypothermia, n = 5. In each group, the infrarenal aorta was occluded for 21 minutes. Final neurologic recovery after restitution of blood flow was graded as acute paraplegia, delayed paraplegia (neurologic deficit developing after initial recovery), or normal. Halothane alone was of no benefit. Hypothermia with any anesthetic was completely protective and reduced neurologic deficits to 0% compared with 91% in controls (p less than 0.05). Thiopental and ketamine treatment each reduced acute paraplegia to 17% (as compared with 61% in controls) and increased delayed paraplegia from 30% in controls to 75% and 50%, respectively (p less than 0.05 for thiopental, p = 0.10 for ketamine). The authors interpret the increase in delayed deficits and decrease in acute deficits as being the result of partial spinal cord protection. These findings document that this model of spinal cord ischemia is sufficiently sensitive to identify interventional treatments that protect the ischemic spinal cord. PMID- 1616379 TI - Emergency coronary artery bypass surgery for failed percutaneous coronary angioplasty. A 10-year experience. AB - Six hundred ninety-nine patients have required emergency coronary artery bypass after failed elective percutaneous coronary angioplasty during the decade September 1980 through December 1990. This represents 4% of 9860 patients having 12,146 elective percutaneous coronary angioplasty procedures during this interval. Emergency coronary artery bypass was required for acute refractory myocardial ischemia in 82%. Hospital mortality rate for all patients was 3.1%; 3.7% in patients with refractory myocardial ischemia but 0.8% in patients without refractory myocardial ischemia, p = 0.08. Postprocedural Q-wave myocardial infarctions were observed in 21% versus 2.4%, p less than 0.0001, and intra aortic balloon pumping was required in 19% with versus 0.8% without refractory myocardial ischemia, p less than 0.0001. Multivessel disease, p = 0.004, age older than 65 years, p = 0.005, and refractory myocardial ischemia, p = 0.08, interacted to produce the highest risk of in-hospital death. Follow-up shows that there have been 28 additional late deaths, including 23 of cardiac causes for a 91% survival at 5 years. Freedom from both late death and Q-wave myocardial infarction at 5 years was 61%. In the group going to emergency coronary artery bypass with refractory myocardial ischemia, the late cardiac survival was 90%, and in those without ischemia, 92% at 5 years, p = not significant. The MI--free survival in the group with refractory ischemia, however, was 56% versus 83% in the group without ischemia, p less than 0.0001. Multivariate analysis showed the highest late event rates for patients with Q-wave myocardial infarction at the initial emergency coronary artery bypass, age older than 65 years, angina class III or IV, and prior coronary bypass surgery. In spite of a continuing high incidence of early acute myocardial infarction and an increasing operative mortality rate (7%) in the latest 3 years cohort of patients, excellent late survival and low subsequent cardiac event rates demonstrate the lasting effectiveness of prompt, successful emergency coronary bypass surgery for failed percutaneous coronary angioplasty. PMID- 1616380 TI - Infected aortic aneurysms. A changing entity. AB - Infected (mycotic) aortic aneurysms are infrequent and, without surgical intervention, usually lead to uncontrolled sepsis or catastrophic hemorrhage. Symptoms are frequently absent or non-specific during the early stages, and a high index of suspicion is essential to make the diagnosis. Surgery performed after rupture carries high morbidity and mortality rates. Bacterial endocarditis with streptococcus pyogenes was the most common cause of infected aortic aneurysm in the pre-antibiotic era. Today, arterial trauma due to iatrogenic manipulation and depressed immunocompetence have become more common risk factors. Staphylococcus aureus and Salmonella are the most frequent bacteria identified. The authors' recent experience in six patients with infected aortic aneurysms who underwent arteriography and computed tomography was reviewed and these diagnostic methods compared. Computed tomography was found to be more sensitive in the diagnosis of the early stages of the disease, allowing for follow-up by serial scans in a noninvasive and less costly manner. Successful treatment, in four of these patients, was accomplished by aneurysmal resection and extra-anatomic bypass or in situ prosthetic reconstruction. A higher clinical awareness of this disease, leading to early computed tomography evaluation and prompt surgical intervention under appropriate and intensive antibiotic therapy, appears to offer the best chance of survival in patients with this difficult condition. PMID- 1616381 TI - Juxtarenal aortic occlusion. AB - The authors' experience with 113 aortic occlusions in 103 patients during a 26 year period (1965 to 1991) is reviewed. The authors found three distinct patterns of presentation: group I (n = 26) presented with acute aortic occlusion, group II (n = 66) presented with chronic aortic occlusion, and group III (n = 21) presented with complete occlusion of an aortic graft. Perioperative mortality rates were 31%, 9%, and 4.7% for each respective group and achieved statistical significance when comparing group I with group II (p = 0.009) and group I with group III (p = 0.015). Group I presented with profound metabolic insults due to acute ischemia and fared poorly. Group II presented with chronic claudication and did well long-term. Group III presented with acute ischemia but did well because of established collateral circulation. The treatment and expected outcome of aortic occlusion depends on the cause. PMID- 1616382 TI - Total IgE in plasma is elevated after traumatic injury and is associated with sepsis syndrome. AB - Gamma E immunoglobulin (IgE) is associated with allergic reactions, but has not been described as being activated after trauma or sepsis. Total plasma IgE concentrations were determined in 32 patients with major traumatic injury, 29 patients undergoing elective abdominal operations, and 30 healthy volunteers. Mean total IgE concentrations were 271.7 ng/mL, 52.3 ng/mL, and 41.3 ng/mL, respectively (p less than 0.01 for each comparison with the trauma group). Total IgE concentrations in trauma patients at the time of admission were not significantly different from elective surgical controls, and tended to increase during the intensive care unit stay. In the trauma group, total IgE concentration was significantly greater in the 18 patients that developed sepsis syndrome compared with those that did not (p = 0.034). These data suggest that allergic mechanisms may be involved in the physiologic response to major traumatic injury and sepsis syndrome, or that other cells known to be involved in the immune responses to trauma and sepsis (macrophages, platelets, and B lymphocytes) may become activated by IgE-dependent mechanisms. PMID- 1616383 TI - Abdominal packing for surgically uncontrollable hemorrhage. AB - Planned intra-abdominal packing for surgically uncontrollable hemorrhage from liver and retroperitoneal injuries exacerbated by hypothermia, acidosis, and coagulopathy regained popularity over the past decade. The authors reviewed 39 patients injured between August 1985 and September 1990; 31 packed for liver injuries, eight for nonliver injuries. The overall mortality rate was 44% (17/39); 9 (23%) exsanguinated, 3 (8%) died of head injuries, 3 (8%) of multisystem organ failure, 2 (5%) of late complications. The mean age was 33.9 +/ 16.2 (range, 16 to 79); there were 26 men and 13 women. Relaparotomy for pack removal was performed 2.0 +/- 1.1 days (range, 1 to 7) after initial operation. The authors identified intraoperative risk factors of pH less than or equal to 7.18, temperature less than or equal to 33 C, prothrombin time greater than or equal to 16, partial thromboplastin time greater than or equal to 50, and transfusion of 10 units or more of blood as highly predictive of outcome. Patients with four to five risk factors (n = 3) had a 100% mortality rate (p less than 0.04); two to three risk factors (n = 12), 83% mortality rate (p less than 0.003), compared with zero to one risk factors (n = 24), 18% mortality rate. Complications developed in six of 22 survivors (27%): 5 abdominal abscesses (23%), 2 wound dehiscences (9%), and 2 enterocutaneous fistulae (9%). Intra abdominal packing will not stop all bleeding; 23% of the patients exsanguinated. In 77%, packing helped achieve hemostasis we believed was not otherwise possible. Packing may be done to prevent the development of acidosis, hypothermia, and coagulopathy or may be done early in the treatment of cold, acidotic patients rather than massive transfusion in the face of surgically uncorrectable bleeding. PMID- 1616384 TI - Abbreviated laparotomy and planned reoperation for critically injured patients. AB - The triad of hypothermia, acidosis, and coagulopathy in critically injured patients is a vicious cycle that, if uninterrupted, is rapidly fatal. During the past 7.5 years, 200 patients were treated with unorthodox techniques to abruptly terminate the laparotomy and break the cycle. One hundred seventy patients (85%) suffered penetrating injuries and 30 (15%) were victims of blunt trauma. The mean Revised Trauma Score, Injury Severity Score, and Trauma Index Severity Score age combination index predicted survival were 5.06%, 33.2%, and 57%, respectively. Resuscitative thoracotomies were performed in 60 (30%) patients. After major sources of hemorrhage were controlled, the following clinical and laboratory mean values were observed: red cell transfusions--22 units, core temperature--32.1 C, and pH--7.09. Techniques to abbreviate the operation included the ligation of enteric injuries in 34 patients, retained vascular clamps in 13, temporary intravascular shunts in four, packing of diffusely bleeding surfaces in 171, and the use of multiple towel clips to close only the skin of the abdominal wall in 178. Patients then were transported to the surgical intensive care unit for vigorous correction of metabolic derangements and coagulopathies. Ninety-eight patients (49%) survived to undergo planned reoperation (mean delay 48.1 hours), and 66 of 98 (67%) survived to leave the hospital. With the exception of intravascular shunts, there were survivors who were treated by each of the unorthodox techniques. Of 102 patients who died before reoperation 68 (67%) did so within 2 hours of the initial procedure. Logistic regression showed that red cell transfusion rate and pH may be helpful in determining when to consider abbreviated laparotomy. The authors conclude that patients with hypothermia, acidosis, and coagulopathy are at high risk for imminent death, and that prompt termination of laparotomy with the use of the above techniques is a rational approach to an apparently hopeless situation. PMID- 1616385 TI - Control of the hypermetabolic response to burn injury using environmental factors. AB - This study was performed to establish the relative efficiency of occlusive dressings and variable ambient temperature (group I) versus no dressings and variable ambient temperature (group II) versus no dressings and electromagnetic heaters (group III) for controlling the postburn hypermetabolic response. Fifteen burn patients and five normal controls (group IV) were studied when subjectively comfortable using partitional calorimetry, after which each patient was cold stressed by sequentially decreasing external energy support, and repeating calorimetry studies and serial plasma catecholamine assays. The percentage increase in heat production above predicted normal values was significantly increased for all groups when cold (C) versus neutral (N) (group I: [N] 24 +/- 24 versus [C] 49 +/- 25%; group II: [N] 46 +/- 35 versus [C] 74 +/- 47%; group III: [N] 21 +/- 20 versus [C] 78 +/- 25%; group IV: [N] -9 +/- 12 versus [C] 16 +/- 10%, p less than 0.05 all comparisons). Plasma catecholamine values did not increase significantly when patients were subjectively cold. These studies do not support the role of catecholamines as the primary mediator in the cause of the postburn hypermetabolic response. Using the patients' subjective comfort status as a guide for external energy support, it is possible to greatly reduce but not to eliminate the hypermetabolic response to burn injury. PMID- 1616386 TI - Significant trends in the treatment of hepatic trauma. Experience with 411 injuries. AB - Several significant advances in the treatment of hepatic injuries have evolved over the past decade. These trends have been incorporated into the overall treatment strategy of hepatic injuries and are reflected in experiences with 411 consecutive patients. Two hundred fifty-eight patients (63%) with minor injuries (grades I to II) were treated by simple suture or hemostatic agents with a mortality rate of 6%. One hundred twenty-eight patients (31%) sustained complex hepatic injuries (grades III to V). One hundred seven patients (83.5%) with grades III or IV injury underwent portal triad occlusion and finger fracture of hepatic parenchyma alone. Seventy-three surviving patients (73%) required portal triad occlusion, with ischemia times varying from 10 to 75 minutes (mean, 30 minutes). The mortality rate in this group was 6.5% (seven patients) and was accompanied by a morbidity rate of 15%. Fourteen patients (11%) with grade V injury (retrohepatic cava or hepatic veins) were managed by prolonged protal triad occlusion (mean cross-clamp time, 46 minutes) and extensive finger fracture to the site of injury. In four of these patients an atrial caval shunt was additionally used. Two of these patients survived, whereas six of the 10 patients managed without a shunt survived, for an overall mortality rate of 43%. Over the past 4 years, six patients (4.7%) with ongoing coagulopathies were managed by packing and planned re-exploration, with four patients (67%) surviving and one (25%) developing an intra-abdominal abscess. One additional patient (0.8%) was managed by resectional debridement alone and survived. During the past 5 years, 25 hemodynamically stable and alert adult patients (6%) sustaining blunt trauma were evaluated by computed tomography scan and found to have grade I to III injuries. All were managed nonoperatively with uniform success. The combination of portal triad occlusion (up to 75 minutes), finger fracture technique, and the use of a viable omental pack is a safe, reliable, and effective method of managing complex hepatic injuries (grade III to IV). Juxtahepatic venous injuries continue to carry a prohibitive mortality rate, but nonshunting approaches seem to result in the lowest cumulative mortality rate. Packing and planned reexploration has a definitive life-saving role when used adjunctively in the presence of a coagulopathy. Nonoperative management of select hemodynamically stable adult patients, identified by serial computed tomography scans after sustaining blunt trauma is highly successful (95-97%). PMID- 1616387 TI - Enteral versus parenteral feeding. Effects on septic morbidity after blunt and penetrating abdominal trauma. AB - To investigate the importance of route of nutrient administration on septic complications after blunt and penetrating trauma, 98 patients with an abdominal trauma index of at least 15 were randomized to either enteral or parenteral feeding within 24 hours of injury. Septic morbidity was defined as pneumonia, intra-abdominal abscess, empyema, line sepsis, or fasciitis with wound dehiscence. Patients were fed formulas with almost identical amounts of fat, carbohydrate, and protein. Two patients died early in the study. The enteral group sustained significantly fewer pneumonias (11.8% versus total parenteral nutrition 31.%, p less than 0.02), intra-abdominal abscess (1.9% versus total parenteral nutrition 13.3%, p less than 0.04), and line sepsis (1.9% versus total parenteral nutrition 13.3%, p less than 0.04), and sustained significantly fewer infections per patient (p less than 0.03), as well as significantly fewer infections per infected patient (p less than 0.05). Although there were no differences in infection rates in patients with injury severity score less than 20 or abdominal trauma index less than or equal to 24, there were significantly fewer infections in patients with an injury severity score greater than 20 (p less than 0.002) and abdominal trauma index greater than 24 (p less than 0.005). Enteral feeding produced significantly fewer infections in the penetrating group (p less than 0.05) and barely missed the statistical significance in the blunt injured patients (p = 0.08). In the subpopulation of patients requiring more than 20 units of blood, sustaining an abdominal trauma index greater than 40 or requiring reoperation within 72 hours, there were significantly fewer infections per patient (p = 0.03) and significantly fewer infections per infected patient (p less than 0.01). There is a significantly lower incidence of septic morbidity in patients fed enterally after blunt and penetrating trauma, with most of the significant changes occurring in the more severely injured patients. The authors recommend that the surgeon obtain enteral access at the time of initial celiotomy to assure an opportunity for enteral delivery of nutrients, particularly in the most severely injured patients. PMID- 1616388 TI - Carotid endarterectomy monitored with transcranial Doppler. AB - Intraoperative transcranial Doppler monitoring of cerebral ischemia during carotid clamping under general anesthesia was done in 238 carotid artery operations, mostly endarterectomy. Depending on the severity of reduction of middle cerebral artery mean velocity, patients were classified as no, mild, or severe ischemia at clamping. With a carotid shunt, velocity was always in the "no ischemia" category during shunting. For patients with no ischemia, stroke was significantly lower without a shunt (2/175 no shunt versus 2/12 shunt). For mild ischemia, shunting did not affect the stroke rate (1/20 no shunt versus 0/9 shunt). For severe ischemia, strokes were less frequent with a shunt (4/9 no shunt versus 0/13 shunt). Intraoperative electroencephalogram predicted most, but not all severely ischemic cases. Carotid back pressure correlated with Doppler velocity, but transcranial Doppler was more helpful. Transcranial Doppler is a new and valuable technique in carotid surgery. PMID- 1616389 TI - The effect of gastrin on growth of human stomach cancer cells. AB - Gastrin is known as a trophic factor for some stomach and colorectal cancer cells; however, the roles of gastrin receptors and the intracellular signal transduction pathways by which gastrin regulates cell growth are still unknown. The authors examined the effect of synthetic human gastrin-17 on growth of human stomach cancer cells (the parent line, AGS-P, and two different clones, AGS-10 and AGS-12), which were established (and have been maintained) in our laboratory. Gastrin stimulated growth of AGS-P and AGS-10 cells, which have gastrin receptors, in a dose-dependent fashion. A highly selective gastrin receptor antagonist, JMV 320, inhibited the growth-stimulatory effect of gastrin on AGS-P cells in a dose-dependent fashion. Concentrations of gastrin (10(-8) to 10(-6) M), which stimulated growth of AGS-P cells, did not affect either cyclic adenosine monophosphate production or phosphatidylinositol hydrolysis. Gastrin (10(-11) to 10(-5) M) mobilized calcium from the intracellular organelles to increases intracellular calcium level in AGS-P cells. The AGS-12 clone has no gastrin receptors, and gastrin did not affect growth or mobilization of intracellular calcium in these cells. Our findings indicate that gastrin stimulates growth of AGS cells through a mechanism that involves binding to specific gastrin receptors that are linked to the system for mobilization of intracellular calcium. PMID- 1616390 TI - Cytokine modulation of Na(+)-dependent glutamine transport across the brush border membrane of monolayers of human intestinal Caco-2 cells. AB - Previous studies have demonstrated that Na(+)-dependent brush border glutamine transport is diminished in septic patients. To examine the potential regulation of this decreased transport by endotoxin, cytokines, or glucocorticoids, the human intestinal Caco-2 cell line was studied in vitro. Na(+)-dependent glutamine transport across the apical brush border membrane was assayed in confluent monolayers of differentiated cells that were 10 days old. Uptake of 50 microM glutamine was determined after a 12-hour incubation with varying doses (10 to 1000 U/mL) of tumor necrosis factor-alpha, interleukin-1, interleukin-6, interferon-gamma, and various combinations of these cytokines. Studies were also done in cells incubated with E. coli endotoxin (1 micrograms/mL) or dexamethasone (1 and 10 microM). Endotoxin, tumor necrosis factor, interleukin-1, and interleukin-6 alone and in combination did not significantly reduce Na(+) dependent glutamine transport across the brush border of Caco-2 cells. Dexamethasone decreased glutamine transport by 20%, but this decrease was not apparent for 48 hours. Interferon consistently decreased glutamine transport by 30%; this was due to a reduction in carrier maximal transport velocity (3427 +/- 783 pmol/mg protein/minute in controls versus 2279 +/- 411 in interferon, p less than 0.05) rather than a change in Km (276 +/- 29 microM in controls versus 333 +/- 74 in interferon, p = not interferon + dexamethasone + tumor necrosis factor + interleukin-1 resulted in a 38% decrease in transport activity. Cytokines and glucocorticoids may work independently and synergistically in regulating Na(+) dependent brush border glutamine transport in human intestinal cells. Whether these signal molecules play a central role in the cause of the diminished brush border glutamine transport that occurs in septic patients requires further study. PMID- 1616391 TI - Patterns of ileal recurrence in Crohn's disease. A prospective randomized study. AB - To gain information on the pathogenesis of ileal recurrence, 86 patients with Crohn's disease undergoing their first ileocolic resection were randomized to receive either an end-to-end (n = 47) or side-to-end (n = 39) anastomosis. The demographic and clinical characteristics of both groups were similar. There were no statistically significant differences between the two groups in postoperative complications or in the subsequent development of symptomatic or documented recurrences. Among the 43 patients with follow-up in the end-to-end anastomosis group, there were 10 documented ileal recurrences (23%), and all involved distal ileum in the characteristic preanastomotic location. Among the 35 patients with follow-up in the side-to-end anastomosis group, there were 11 documented recurrences (31%, not significant). The ileal recurrence pattern could be determined accurately in five of these 11 patients and involved the ileum adjacent to the colon, but spared the distal ileum in the blind pouch. This study suggests that the fecal stream and reflux of colonic contents are important factors in determining the pattern of ileal recurrence after ileocolectomy for Crohn's disease. PMID- 1616392 TI - Evaluation of the relative efficacy of various antimalarial drugs in Nigerian children under five years of age suffering from acute uncomplicated falciparum malaria. AB - A parallel group-randomized comparison of the therapeutic efficacy of chloroquine (CQ), amodiaquine (AM), quinine (QN), sulphadoxine-pyrimethamine (S-P), mefloquine 15 mg kg-1 (M15) and mefloquine 25 mg kg-1 (M25) in acute symptomatic uncomplicated falciparum malaria was carried out in 325 children under the age of five years in Ibadan, southwestern Nigeria, using the 28-day in vivo test. The parasitological cure rate, assessed only up to day 14, was 85% in the CQ group and 100% in the other groups. The mean parasite and fever clearance times were, respectively, 2.64 and 1.20 days in the CQ-sensitive subgroup, 2.32 and 1.13 days in the AM group, 2.27 and 1.17 days in the QN group, 2.23 and 1.76 days in the S P group, 2.13 and 1.10 days in the M15 group, and 2.07 and 1.09 days in the M25 group. The CQ-treatment failures (seven of 46 patients) were successfully treated with 25 mg kg-1 mefloquine, with parasite and fever clearance times of 1.73 and 1.0 days respectively. The study shows that, in Nigeria, CQ is now less effective than AM, S-P, QN and M in acute falciparum malaria in the group most vulnerable to the infection (the under-five-year-olds).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616393 TI - Survival of Trypanosoma brucei brucei in cerebrospinal fluid. AB - Different compositions of artificial cerebrospinal fluid (CSF) and the CSF from sleeping sickness patients both with and without late-stage [i.e. central nervous system (CNS)] involvement were evaluated for their abilities to support survival of Trypanosoma brucei brucei. Artificial CSF, containing the major electrolytes, amino acids and carbohydrate components of healthy fluid, was equivalent to the CSF from patients without CNS involvement (survival time 20 hours). Normal CSF does not therefore contain substances which deter the parasite. The CSF from the late-stage patients did not support survival for longer than 10 hours, probably because it contained increased numbers of lymphocytes and antibodies. PMID- 1616394 TI - Drug targeting with polyalkylcyanoacrylate nanoparticles: in vitro activity of primaquine-loaded nanoparticles against intracellular Leishmania donovani. AB - The efficacy of primaquine-loaded polyisohexylcyanoacrylate (PIHCA) nanoparticles was evaluated using J774G8 macrophage-like cells infected with Leishmania donovani: as an in vitro model of visceral leishmaniasis. The in vitro antileishmanial activity of primaquine-loaded nanoparticles showed a 21-fold increase in ED50 compared with free primaquine. Although unloaded PIHCA nanoparticles also exhibited a significant anti-leishmanial effect, the loaded nanoparticles showed a synergistic effect compared with a mixture of unloaded nanoparticles and free primaquine at equivalent concentrations. Primaquine release and isohexanol production were evaluated in a lysosomal fraction; the correlation of both with protein concentration and the rapid drug release indicate the processes are associated with an enzymatic degradation. The results indicate that PIHCA and other polyalkylcyanoacrylates may be useful for targeting drugs at intracellular Leishmania, and that the unloaded carrier itself could be of interest in experimental chemotherapy of leishmaniasis. PMID- 1616395 TI - Substituted methyl benzimidazole carbamate: efficacy against experimental cysticercosis. AB - Methyl [5-([4-(2-pyridinyl)-1-piprazinyl] carbonyl)-1H benzimidazole-2-yl] carbamate, a broad spectrum anthelmintic, was tested against Cysticercus fasciolaris in rats and the cysticercoids of Hymenolepis nana in beetles. A dose of 50 mg kg-1, given intraperitoneally (i.p.) to infected rats on 10 alternate days, was found most effective, killing all mature cysticerci. The same dose, given on each of five days, either from the fifth day prior to infection or the sixth day following infection, fully arrested the establishment of cysticerci. A single prophylatic dose of 500 mg kg-1, given intramuscularly (i.m.), protected rats against challenge with Taenia taeniaeformis eggs for 10 days. The test compound, mebendazole and praziquantel were all totally ineffective against mature cysticercoids in grain beetles but, of the beetles fed the drugs in flour, 66.3%, 50% and 83.8%, respectively, failed to support the development of immature cysticercoids. The effective cysticidal action of the compound makes it a candidate medical anthelmintic. PMID- 1616396 TI - Chemotherapy of human cystic echinococcosis: comparative efficacy of mebendazole and albendazole. AB - The relative efficacy of mebendazole (MEB) and albendazole (ALB) was tested by treating 51 patients with single, multiple and multi-organ hydatid cysts; 28 patients were treated with MEB, 50-70 mg kg-1 body weight daily for six to 24 months, and 23 with ALB, 10 mg kg-1 body weight daily in four courses of 30 days with 15-day intervals between courses. The therapeutic effect during the follow up was assessed by ultrasonography, computerized tomography and chest X-ray. The criteria used when assessing the results were: 'success', evidence of effect on all cysts; 'partial success', evidence of effect on some of the cysts; and 'no success', no changes in cyst morphology. Treatment with MEB was successful in eight cases (28.6%), partially successful in eight (28.6%) and unsuccessful in 12 (42.8%). Treatment with ALB was successful in 10 cases (43.5%), partially successful in 10 (43.5%) and unsuccessful in three (13.0%). PMID- 1616397 TI - Immune status during albendazole therapy for hydatidosis. AB - Immunological monitoring of cystic hydatid patients undergoing medico-surgical management has revealed that it is possible to assess individual host responses throughout therapy and subsequently be guided by the results obtained. The analysis has involved the demonstration of variation in haemagglutination antibodies, specific IgG and IgM immunoglobulins and circulating immune complexes before, during, and months after albendazole therapy. PMID- 1616398 TI - Prevalence of Toxoplasma gondii antibodies in goats in Sri Lanka. PMID- 1616399 TI - Immunological localization of blood pl antigen in tissues of Echinococcus granulosus. PMID- 1616400 TI - Bacteriology of abscesses complicating bites of lance-headed vipers. PMID- 1616401 TI - A simplified method for identifying subspecies and strain groups in Trypanozoon by isoenzymes. AB - To characterize trypanosomes from the subgenus Trypanozoon, 272 stocks in 111 zymodemes were analysed by the polymorphisms seen in a rationalized range of nine enzymes, resolved by electrophoresis, mostly on cellulose acetate. Several highly polymorphic or invariant enzymes used previously were omitted, while two new enzymes, NHD and SOD were included; the isoenzymes seen for SOD were interpreted as two separate enzymes, SODA and SODB. Isoenzyme band patterns were analysed by two complementary numerical methods to elucide taxonomic relationships within the subgenus; groups of zymodemes corresponding to subspecies and strain groups were defined, which agreed closely with previous studies. Except for one zymodeme, Trypanosoma evansi could not be clearly distinguished from the bouafle strain group. This strain group had enzymic features that overlapped to some extent those of the busoga group. Trypanosoma brucei gambiense and the zambezi, kakumbi, kiboko and sindo groups were clearly defined. Eight zymodemes could not be classified. A rapid identification system using a limited number of enzymes is presented. PMID- 1616402 TI - [CT vs MRI in the diagnosis of acute stroke]. AB - 70 patients who had suffered an acute stroke (52 ischaemic and 18 haemorrhagic) were studied with CT and MR, performing both techniques during the first week of disease and correlating the findings with the clinical data. MR proved superior in the detection of ischaemic infarcts, specially those in the posterior territory and with a small size; it was also superior to CT in the detection of leukoaraiosis and the demonstration of vascular obstructions. CT failed to detect a small brain stem haemorrhage secondary to bleeding of a cavernoma, while its performance was similar to that of MR in the remaining cases. In all patients with intracerebral haemorrhages, including two who were examined on the first day, an area of increased density was evidenced in the T1 sequences. It is concluded that CT, due to its greater availability and easiness of performance, must be maintained as first choice in acute stroke in order to differentiate haemorrhage from ischaemia, while MR may provide additional information in selected cases. PMID- 1616403 TI - [Various capabilities involved in memory and the disturbances caused by amnesia syndromes]. PMID- 1616405 TI - Pathologists in the 1990s and in the 21st century. Physicians providing quality diagnoses, laboratory information, and therapies for patient care. PMID- 1616404 TI - [Response to the cold test in patients older than 60 years of age with ischemic cerebrovascular disease]. AB - We have realized the test of cold in a group of patients with ischemic cerebrovascular attack (AVCi) and in a control group. The comparison of results shows a different vascular reactivity into the groups. At present, it is unknown if there is a relation of this finding with the AVCi occurrence. PMID- 1616406 TI - Professional satisfaction. Can it exist for the pathologist in 2001? PMID- 1616407 TI - Another look at manpower studies. PMID- 1616408 TI - Pathology trainee manpower. Historical perspectives. AB - Discussions of pathology manpower typically involve short-term projections. For example, the best current data indicate a significant shortage of community hospital/private-laboratory pathologists over the 5-year period from 1988 through 1993. Even though such short-term predictions are important in the debate over strategic planning in pathology, they need to be placed in a broader historical context. Therefore, we present the long-term trends in pathology trainee manpower. These trends indicate why predictions of a shortage should not come as a surprise. PMID- 1616409 TI - College of American Pathologists Foundation Conference VI: A Profile of the Pathologist in the Year 2001. September 5-8, 1991. PMID- 1616410 TI - Probable impact of physician payment reform. A 40-year perspective. PMID- 1616411 TI - What will the pathologist be doing in 2001? Speculations of a hospital practitioner. AB - The 21st century looms ahead, and physicians are increasingly anxious about what the practice of medicine will be like in the future. Pathologists, like other physicians, are holding conferences and writing papers in an attempt to predict what lies ahead. From the perspective of one community pathologist, the future looks bright as far as work opportunities. The jobs that will need to be filled will include familiar ones and numerous new tasks. There will be plenty of jobs; but will there be enough skilled pathologists to fill these positions? The answer depends on our ability to attract the needed physicians into pathology and to give them the needed variety of skills to survive in a new work environment. PMID- 1616412 TI - Next-generation technologies. Impact on the work load of the pathologist. AB - Technologies emerging and evolving in the 1990s, particularly in molecular biology, therapeutics, computerization, and information management, will alter the type of work and work load of the pathologist. In general, new technologies will increase the work load of pathologists. However, the extent to which new medical technologies affect pathology will be modulated by socioeconomic factors, given the relationship between new technology and increased medical costs. Pathologists may choose to embrace many new technologies and should play an active role in technology assessment to ensure the appropriate use of new diagnostic procedures. PMID- 1616413 TI - Why manpower surveys in pathology? Use of the National Pathology Manpower Database. AB - The National Pathology Manpower Database was developed in 1986 as a representative subset of pathologists engaged in community hospital and private laboratory practice. Manpower surveys in 1987, 1988, and again in 1991 using the National Pathology Manpower Database have consistently shown a greater projected attrition in the number of pathologists from this practice setting than the number of new pathologists entering the specialty. Without periodic surveys of pathologists using a valid sample such as the National Pathology Manpower Database, it is likely that future decisions regarding the supply and need for pathologists would be based on the American Medical Association Master File of Physicians that does not specify practice activity or reflect any manpower kinetics. PMID- 1616414 TI - Problems and opportunities in pathology manpower. AB - Speculations regarding the future of pathology manpower most often depend on whether the perspective taken is pessimistic or optimistic. In this article, I propose that the pessimist-optimist options are inadequate. To speculate responsibly about the future, our first task must be to understand clearly the present problems and opportunities. Problems facing pathology are numerous: (1) practitioners are retiring at an increasing rate, (2) inadequate numbers of newly trained pathologists are available to fill vacancies, (3) training program numbers continue to decline, (4) attrition of trainees is substantial, and (5) recruitment of new trainees encounters significant barriers. Despite these problems, significant opportunities to improve training program environments, decrease attrition, and increase recruitment are available. The future of pathology will depend on how we respond to the problems and opportunities that we currently face. PMID- 1616415 TI - Are we training the next generation of pathologists correctly? PMID- 1616416 TI - The pathologist of 2001 as seen in 1991. PMID- 1616417 TI - Can continuing medical education prepare the current practitioner for the 21st century? AB - The traditional approach to continuing medical education (CME) will be inadequate to prepare the practicing pathologist for the 21st century. Seminars at regional or national meetings, audiovisual presentations, and similar CME activities are useful to provide updates or to fill in more detailed information in the basic knowledge that all pathologists must acquire during their training. Different, more imaginative approaches will be necessary for the pathologist wishing to acquire the necessary knowledge and skills to utilize the newly developing techniques in pathology, such as flow cytometry, image analysis, and the myriad diagnostic procedures based on molecular biology. Self-directed learning will continue to be an essential approach to CME, and the availability of computer programs, including videodisks, will be increasingly effective. However, it should be acknowledged that self-directed learning has been available since the invention of the printing press. The current pressure for public accountability of medical practitioners clearly indicates that pathologists must accept the reality that CME will not be recognized unless it is provided by an accredited organization and attendance is documented. Pathologists should anticipate institution of recertification procedures involving peer review, which will require documentable CME. This CME will be based on needs assessment, educational objectives, more effective formats, and evaluation of whether CME, in fact, improved the pathologist's effectiveness in practice. The academicians have their sabbaticals to refresh their knowledge and explore new fields; perhaps minisabbaticals should be arranged for both the academicians and the practicing pathologist who cannot be away from his or her responsibilities for 6 months or 1 year. The medical specialty societies are the most suitable groups for organizing these programs, although the actual programs must be provided in the laboratories that actually perform the procedures. PMID- 1616418 TI - College of American Pathologists Foundation Conference VI: a profile of the pathologist in the year 2001--summary of the conference. PMID- 1616419 TI - College of American Pathologists Foundation Conference VI. A profile of the pathologist in the year 2001--predictions and recommendations. Board of Directors of the College of American Pathologists Foundation. PMID- 1616420 TI - Continuous quality improvement. Autologous blood donations. PMID- 1616421 TI - Preoperative autologous blood donation in 612 hospitals. A College of American Pathologists' Q-Probes study of quality issues in transfusion practice. AB - We compared predeposit autologous blood utilization practices in 612 hospitals (where 107,559 autologous and 2,504,522 homologous units were transfused in all of 1989). Participating blood bankers prospectively followed up donors who presented for initial donation during an 11-week period in early 1990. They recorded the number of autologous donors whose blood was drawn (n = 22,276); units that were donated (n = 40,163), transfused (n = 23,988), crossed over (n = 937), and discarded (n = 15,443); and donors transfused with autologous blood only (n = 11,923) or donors who received homologous blood (n = 2002). Most donors (89.7%) avoided homologous blood, including donors (39.5%) who did not require transfusion. Units that were donated for low-risk surgery represented 23.1% of all units that were collected, and the rate of donation for these procedures was directly proportional to the percentage of donors who did not require transfusion and to the discard rate. We concluded that a major focus of quality improvement in autologous transfusion practice should be the reduction of donations for surgical procedures for which blood replacement is rarely needed. PMID- 1616422 TI - Toluidine blue in the detection at autopsy of perineal and anal lacerations in victims of sexual abuse. AB - Toluidine blue dye can be used at autopsy to aid in the detection of genital and anal injuries due to child sexual abuse. Four case examples are presented. PMID- 1616424 TI - Diagnostic efficiency of carcinoembryonic antigen and CA125 in the cytological evaluation of effusions. AB - In our previous study, the combination of the concentrations of carcinoembryonic antigen (CEA) and CA125 and the findings from cytological examination in 189 benign and malignant pleural and peritoneal effusions was useful in the diagnosis/classification of malignant effusions. Sensitivity of CEA (level, greater than 5 ng/mL) was 68%; specificity was 99% for the diagnosis of malignant effusions secondary to carcinoma of the lung, breast, gastrointestinal tract, and mucinous carcinoma of the ovary. Sensitivity of CA125 (level, greater than 5000 U/mL) was 85%; specificity was 96% for the diagnosis of malignant effusions in carcinoma of the ovary, fallopian tube, and endometrium. We now expanded the study to include 840 pleural and peritoneal effusions (benign, n = 520; malignant, n = 320) and analyzed the data by the statistical method of Rudolph and colleagues. Based on new cutoff values, ie, CEA level at 6.3 ng/mL and CA125 level at 3652 U/mL, the sensitivities for detection of malignant effusions secondary to carcinomas of the lung, breast, and gastrointestinal tract and mucinous carcinoma of the ovary varied between 75% and 100%; specificity was 98%. Sensitivity of CA125 for detection of malignant effusions from mullerian epithelial carcinoma was 71%; specificity was 99%. The elevated CEA fluid level alone helped to diagnose malignant effusions of the gastrointestinal tract in 54%, breast in 19%, and lung in 16%. The high CA125 fluid level was predictive of mullerian epithelial carcinoma. Adjunctive use of CEA and CA125 levels in fluid enhances the sensitivity of cytological diagnosis and may be predictive of the primary site in patients who present with carcinoma of an unknown primary source. PMID- 1616423 TI - Evidence of cytotoxic T-cell destruction of epidermal cells in human graft-vs host disease. Immunohistology with monoclonal antibody TIA-1. AB - A newly described mouse monoclonal IgG1 antibody, TIA-1, binds serine esterase positive granule membranes of cytotoxic human T cells and is a candidate for an effector molecule involved in T-cell cytolytic mechanisms analogous to those of the perforin system. We performed immunohistologic studies on frozen human skin (n = 5) and lip (n = 21) sections as well as on control frozen sections of tonsils, purified cytolytic T (CD8) cells, and B cells using an indirect immunoperoxidase system. We found a strong association of TIA-1+ cells with CD8+ cells invading the epidermis in lip and skin lesions of graft-vs-host disease in human marrow allograft recipients, as well as a sharp geographic association of TIA+ lymphocytes with CD8+ regions in human tonsil sections. Double staining of CD8 and TIA-1 antigens with fluorescein isothiocyanate and Texas red confirmed that 80% to 90% of the CD8 cells were TIA-1+ in the epidermal infiltrates. Leu-7 activity (natural killer cell) was minimal and found in only three of 17 lip biopsy specimens. These data provide new evidence that direct cytolytic attack by donor T lymphocytes is the mechanism of epithelial target cell killing in human graft-vs-host disease. PMID- 1616425 TI - Human pulmonary hypoplasia. Statistical, morphological, morphometric, and biochemical study. AB - Human pulmonary hypoplasia was studied statistically and pathologically in a large series of autopsy cases. Multiple logistic regression analysis indicated five independent risk factors from 10 statistically significant factors for pulmonary hypoplasia: (1) hydrops fetalis; (2) renal anomalies; (3) hernia, including diaphragmatic hernia and omphalocele; (4) skeletal anomalies; and (5) abnormalities of amniotic fluid, such as oligohydramnios and polyhydramnios. The characteristics of pulmonary hypoplasia for each factor were defined by morphological, morphometric, and biochemical methods. All bronchiolar branching, acinar complexity, and acinar maturation were retarded in hypoplastic lungs with hydrops fetalis, renal anomalies, affected side of diaphragmatic hernia, omphalocele, and skeletal anomalies. Only acinar complexity and maturation were impaired in the lung with oligohydramnios due to prolonged rupture of membranes. The pathogenesis of pulmonary hypoplasias should be considered differently with each associated anomaly and time of impairment. While impairment in early gestational stage before 16 weeks' gestation results in both reduced bronchiolar branching and retarded acinar development, that, at late stage, influences only acinar development. PMID- 1616426 TI - Sudden death in early infancy due to delayed cardiac tamponade complicating central venous line insertion and cardiac catheterization. AB - Cardiac tamponade is an unusual cause of sudden death in the first weeks of life. We present two cases of cardiac tamponade in the neonatal period that caused death 5 to 6 days following the insertion of intracardiac lines, to draw attention to the possibility of a "delay phenomenon" between the time of the initial procedure and the occurrence of sudden and unexpected death. The presence of blood or clear fluid within the pericardial sac should prompt careful examination of the myocardium for small foci of traumatic damage, particularly when the fluid is under pressure or of large volume. Although the development of circulatory impairment or shock in the days following central line insertion or catheterization raises the possibility of tamponade, it should be noted that sudden death may occur in the absence of any significant antemortem symptoms or signs. PMID- 1616427 TI - The precision of duplicate prothrombin time and partial thromboplastin time assays in neonates. AB - An evaluation of duplicate prothrombin time (PT) and activated partial thromboplastin time (PTT) assays was performed in 277 neonatal samples. Performance criteria were analyzed to determine whether single vs duplicate procedures could be utilized reliably without exposing the neonates to the risk of erroneous PT and PTT results. In addition, we evaluated whether this approach might decrease phlebotomy and hence reduce the number of blood transfusions administered. For PT assays, 97.5% (270/277) of the duplicate results were different by 1 second or less. Only 2.5% (7/277) differed by 3 seconds. For PTT duplicates, 75.0% (207/277) of the values were different by 2 seconds or less and 13.0% (36/277) by 2 to 4 seconds. An additional 12.3% (34/277) were discrepant by as many as 4 seconds. The largest discrepancies occurred in specimens with markedly elevated PT and PTT results, indicative of a significant coagulopathy. In addition, heparin neutralization was performed successfully in 22 neonatal blood specimens showing either partial or full correction of PTT values due to heparin specimen contamination. This study indicates that single PT and PTT assays as well as heparin neutralization tests can be accurately performed and may be able to reduce blood donor exposure by as many as one blood transfusion every 2 to 3 days of hospitalization. PMID- 1616428 TI - Disseminated microsporidiosis (Encephalitozoon hellem) and acquired immunodeficiency syndrome. Autopsy evidence for respiratory acquisition. AB - Microsporidia are obligate intracellular protozoal parasites that infect a variety of cell types in a broad range of invertebrates and vertebrates. They have recently come to medical attention due to the increased frequency with which members of two microsporidian genera, Enterocytozoon and Encephalitozoon, are being diagnosed in patients with the acquired immunodeficiency syndrome (AIDS). The majority of published reports of human microsporidiosis describe Enterocytozoon infection of small intestinal enterocytes. In addition, a growing number of AIDS patients have been identified with infection due to the two species of Encephalitozoon-Encephalitozoon cuniculi and Encephalitozoon hellem, observed in conjunctival, corneal, and, recently, sinonasal tissues. However, there are scant data regarding the systemic pathology and epidemiology of these infections. This article describes a patient with AIDS who died with systemic Encephalitozoon infection. The etiologic microsporidian was found to be E hellem by using antemortem biochemical and antigenic analyses. A complete autopsy, the first to be reported in a patient with this infection, revealed organisms in the eyes, urinary tract, and respiratory tract. A surprising observation was the occurrence of numerous organisms within the lining epithelium of almost the entire length of the tracheobronchial tree, suggestive of respiratory acquisition. Detailed light and electron microscopic findings and the biological and diagnostic features of microsporidiosis are discussed. PMID- 1616429 TI - Yellow lens effects upon visual acquisition performance. AB - Twenty subjects made a total of 400 threshold visual acquisitions of T-38 aircraft approaching from 9 miles out. Half of the acquisitions were made with the subjects wearing yellow ophthalmic filters, and the other half without filters. No overall statistically significant difference in acquisition performance due to the use of yellow filters was found. PMID- 1616430 TI - Contact lens wear with the USAF Protective Integrated Hood/Mask chemical defense ensemble. AB - The Protective Integrated Hood/Mask (PIHM) chemical defense aircrew ensemble blows air from the mask's plenum across the visor at a rate of approximately 15 L/min in order to prevent fogging of the visor and to cool the aircrew member's face. This study was designed to determine the effect of the PIHM airflow on soft contact lens (SCL) dehydration, contact lens comfort, and corneal integrity. There were 26 subjects who participated in this study: 15 SCL wearers, 6 rigid gas-permeable (RGP) wearers, and 5 nonspectacle wearing controls. Contrast acuity with the 3 Regan charts, subjective comfort, and relative humidity (RH) and temperature readings under the PIHM mask were monitored every 0.5 h during 6-h laboratory rides. Slit-lamp examinations and SCL water content measurements with a hand-held Abbe refractometer were made before and after the rides. High RH under the mask may have accounted for the moderate SCL dehydration (8.3%), no decrease in contrast acuity for any group, and lack of corneal stress. Although all groups experienced some inferior, epithelial, punctate keratopathy, RGP wearers had the most significant. SCLs performed relatively well in the PIHM mask environment. Testing with other parameter designs is necessary before recommending RGPs with the PIHM system. PMID- 1616431 TI - Determination of a pressure breathing schedule for improving +Gz tolerance. AB - A base of empirical data for developing optimal pressure breathing during +Gz (PBG) schedules is lacking. Relaxed +Gz-intensity tolerance with PBG was measured during gradual +Gz-onset rate centrifuge profiles using standard lightbar criteria. Constant PBG levels ranging from 18-73 mm Hg were randomly assigned. G suit pressure followed the standard or an increased inflation schedule. Nine subjects wore a jerkin, CSU-15/P G-suit, and TLSS helmet and mask. With mean mask cavity pressures of 0, 18, 38, 60, and 73 mm Hg, corresponding +Gz-tolerances (mean +/- S.E.M.) were: 5.3 +/- 0.2, 5.8 +/- 0.1, 6.6 +/- 0.2, 7.3 +/- 0.3, and 7.5 +/- 0.3 Gz (linear correlation, r = 0.994). Increased G-suit pressure did not change the +Gz-tolerance improvement with PBG. The inverse of individual subject regression slopes ranged from 22.6 to 58.1 mm Hg/+Gz. Considering additional factors and adequate +Gz protection for all subjects while relaxed, the proposed schedule would apply 42 mm Hg PBG/+Gz beginning at +3.3 Gz with a maximum pressure of at least 73 mm Hg. PMID- 1616432 TI - Histaminergic response to Coriolis stimulation: implication for transdermal scopolamine therapy of motion sickness. AB - The blood levels of histamine and 5-hydroxytryptamine (5-HT) in 10 subjects, with or without administration of the transdermal therapeutic system of scopolamine (TTS-S), were measured following motion sickness (MS) induced by Coriolis stimulation. Histamine and 5-HT were assayed using the fluorometric method. The results demonstrated that the blood levels of histamine increased significantly following MS and were even higher in the subjects using TTS-S, but we found neither significant changes in the blood levels of 5-HT following MS nor any effect of TTS-S on it. The results suggest that histamine contributes to the development of MS, and scopolamine may exert its anti-MS action by affecting the histaminergic system as well as the acetylcholinergic system; there may not be a definite relation between 5-HT and the development of MS. PMID- 1616433 TI - Effect of hypobaric hypoxia on fiber type composition of the soleus muscle in the developing rat. AB - The fiber type composition of the soleus muscle was investigated in male Sprague Dawley rats exposed to hypobaric hypoxia of 460 mm Hg from 5 to 12 weeks of age. The muscle fibers were classified as fast-twitch oxidative (FO) and slow-twitch (S) on the basis of adenosine triphosphatase (ATPase) and succinate dehydrogenase (SDH) reactions. Intermediate fibers (INT) with intermediate ATPase and high SDH reaction intensities were also examined. A type shift of muscle fibers from FO to INT and S was found in the control group during development. After exposure to hypoxia, the hypoxia group had a significantly greater percentage of FO fibers than the age-matched control group. There was no significant change in the total number of fibers in the muscle during development and after exposure to hypoxia. These results indicate that the increased percentage of FO fibers found in the developing rat under hypoxic conditions is due to a hypoxia-induced inhibition of the type shift of muscle fibers from FO to S during development. PMID- 1616434 TI - Use of a motion sickness history questionnaire for prediction of simulator sickness. AB - This research assessed the usefulness of the Motion History Questionnaire (MHQ) for the prediction of simulator sickness, a form of motion sickness experienced by pilots training in ground-based flight simulators. Four MHQ scoring keys were compared: (1) the original MHQ key which had been validated on a sample of U.S. Navy student pilots exposed to Coriolis forces, (2 and 3) two keys which had been validated on a sample of civilian college students exposed to simulated ship motions, and (4) a simulator sickness key empirically derived in the present research and cross-validated. Navy and Marine Corps aviators (N = 456) filled out the MHQ prior to their regularly scheduled flight simulator training and were divided into validation and cross-validation samples. All scoring keys were predictive of reported symptoms of sickness, but highest correlations were obtained with the empirically-derived simulator sickness (SS) key. It is suggested that the SS key be used for self-testing so that pilots may be made aware of their risk for developing simulator sickness. PMID- 1616435 TI - Sustained attention and serial responding in heat: mental effort in the control of performance. AB - The effects of heat (40 degrees C) on sustained attention and serial responding were studied in a simple reaction time task and a serial four choice reaction time task, respectively. Core temperature (Tc), heart rate variability (HV) and subjective reactions were monitored during the 80 min of exposure time. Simple reaction time performance and accuracy in the serial choice reaction time task deteriorated significantly in heat. In the serial choice reaction time task, the effects of heat on response times and on HV were correlated. Performance and level of Tc were not correlated, but a relationship was found between performance and rate of Tc change. Results are discussed in relation to the thermophysiological status of the subjects and the compensatory mechanism of effort allocation. It is proposed that task characteristics regulate the degree of activity of this compensatory mechanism. PMID- 1616436 TI - Cervical injuries during high G maneuvers: a review of Naval Safety Center data, 1980-1990. AB - As aircraft capable of sustaining high "G" maneuvers enter the U.S. Navy Fleet, the reported incidence of cervical injury to aircrew seems to have increased. To determine the extent of the problem, personal injury reports submitted to the Naval Safety Center were reviewed for the 10-year period from 1980 to 1990. In addition, confidential questionnaires were sent to flight surgeons supporting fighter/or fighter-attack units. The data collected were statistically analyzed. The incidence of cervical injuries, defined as at least one day's absence from the flight schedule, was computed. Other subjective factors, such as the type helmet worn, the cockpit position flown and the type of mission profile completed, were examined. As might be expected, the most common offender was air combat maneuvering. The most common aircraft was the F/A18, but the radar intercept officer position in the F14B was also a significant contributor. The most common injury pattern reported was a simple muscle strain. Cervical pain after high "G" missions poses a potential threat to combat readiness. However, the use of the newer lightweight helmet seems to have reduced the severity. Muscle strengthening exercises appear to help in prevention. Treatment is successful in most cases with minimal or no residuals noted. As yet, there exist little official data to support the notion of a major problem. PMID- 1616437 TI - Thyroid hormone changes during military field operations: effects of cold exposure in the Arctic. AB - This study examined the effect of prolonged physical activity in a cold environment upon circulating thyroid hormone levels. A secondary focus of the study involved the role of nocturnal habitat upon the thyroidal responses to the physical activity and cold exposure. Military personnel exposed to 10 d of field based operations in the arctic region of Norway were studied. Blood samples were collected before (day 1), and at days 5 and 10 of the operations. Levels of total T4, free T4, total T3, free T3, and thyroid binding globulin were assessed in all blood samples. The results indicated considerable, significant (p less than 0.05) decreases in total thyroid hormone levels, while relative increases of free fractions of the hormones occur with the 10-d operations in the Arctic. However, no significant influence on thyroidal responses were observed due to the nocturnal habitat that the subjects lived in. The hormonal alterations noted are possibly brought about by the combined effects of physical activity and cold exposure acting synergistically to alter thyroid physiology (e.g., most likely the protein carrier binding affinity). PMID- 1616438 TI - Inner ear barotrauma: a case for exploratory tympanotomy. AB - A case of inner ear barotrauma (IEBT) due to an hypobaric chamber experience is presented. IEBT is an exceedingly rare condition in aviation. In the case described, the diagnosis was initially unsuspected due to accompanying middle ear barotrauma. The underlying etiology, the diagnosis, and management of IEBT are discussed. PMID- 1616439 TI - Menstrual history in altitude chamber trainees. AB - Previous studies have determined a higher rate of altitude-induced decompression sickness (DCS) in women than in men. Women are reportedly at higher risk for developing DCS during menses. A study of menstrual history in women completing altitude chamber training without developing DCS has never been accomplished. The purpose of this study was to collect and analyze menstrual history in these women. Thirteen U.S. Air Force Aerospace Physiology Units participated in a USAF approved survey for 1 year. After completing altitude chamber flights, data on age, day of menstrual cycle (DMC), birth control pill use (BCP), and mean durations of menstrual cycle and menses were collected. There were 508 responses analyzed. There was no differences between mean duration of menstrual cycle and menses in the Yes (Y) and No (N) BCP groups. Y and N BCP groups were equally distributed across the menstrual cycle. Women completing altitude chamber training without developing DCS appear to be evenly distributed across their menstrual cycle, with use of BCPs not affecting their susceptibility to DCS. PMID- 1616440 TI - Laser surgery procedures in the operational KC-135E aviation environment. AB - The operational aviation and space environments present a potential for surgical trauma to aircrew and passengers. Current wound care techniques for trauma in the aviation and space medicine environment focus on classical surgical management of wounds. Medical lasers used in these environments can provide rapid control of bleeding wounds, reduce aircraft environmental contamination from body fluids and secretions, and foster rapid triage of injured personnel. Self-contained and reusable medical lasers have the potential to reduce the material supply of medical kits in the aviation and space environment. A miniaturized carbon dioxide laser was used to establish protocols and procedures for use on operational military KC-135E aircraft. Laser surgery was performed to demonstrate laser efficacy and safety in flight. PMID- 1616441 TI - Comparison of current Shuttle and pre-Challenger flight suit reach capability during launch accelerations. AB - The Challenger accident prompted the creation of a crew escape system which replaced the former Launch Entry Helmet (LEH) ensemble with the current Launch Entry Suit (LES). However, questions were raised regarding the impact of this change on crew reach capability. Our study addressed the question of reach capability and its effect on realistic ground-based training for Space Shuttle missions. Eleven subjects performed reach sweeps in both the LEH and LES suits during 1 and 3 Gx acceleration trials in the Brooks AFB, TX, centrifuge. These reach sweeps were recorded on videotape and subsequently analyzed using a three dimensional motion analysis system. The ANOVA procedure of the Statistical Analysis System (SAS) program was used to evaluate differences in forward and overhead reach. The results showed that the LES provided less reach capability than its predecessor, the LEH. This study also demonstrated that, since there was no substantial difference between 1 and 3 Gx reach sweeps in the LES, realistic Shuttle launch training may be accomplished in ground-based simulators. PMID- 1616443 TI - The future of aerospace medicine: dissolution or growth? PMID- 1616442 TI - A new generation of U.S. Army flight helmets. AB - Head injuries are the most common cause of fatal injury in helicopter crashes. For over 80 years, the U.S. Army has used crash investigation studies to redesign flight helmets. This paper describes the evolution of the new fielded U.S. Army helmet, the Sound Protection Helmet No. 4B (SPH-4B), and compares its protective features to its predecessors, especially the SPH-4. A major contribution to the helmet design process was made by the Aviation Life Support Equipment Retrieval Program (ALSERP), a functional program at the U.S. Army Aeromedical Research Laboratory (USAARL). ALSERP has analyzed more than 500 helmets involved in crash events since 1972. Based on these studies of critical safety factors, the Army has developed and deployed the SPH-4B, a new helmet with improved energy absorption, retention, and stability. PMID- 1616444 TI - Functional cytology of the human testis. AB - The seminiferous tubular compartment of the human testis occupies about two thirds of the volume of the organ and is supported by loose connective tissue containing the Leydig cells. Sertoli cells extend from the basal lamina to the lumen of the seminiferous tubule and provide structural and functional support to the germ cells which proliferate and mature through the complex process of spermatogenesis, lasting for approximately 70 days. Histological examination of the human seminiferous epithelium gives the impression of a very irregular pattern of germ cell development but recent cytological, ultrastructural and computer-modelling studies have shown that the arrangement of germ cells within the seminiferous tubules is in fact highly organized into a helical pattern based upon the geometry of concentric spirals. Thus the human spermatogenic cycle is precisely regulated in accordance with the more familiar ordered arrangements of germ cells seen in most non-human primates and other mammalian species. The population of Leydig cells in the adult human testis represents the third and final phase of their developmental history, preceded by distinct neonatal and, earlier, fetal Leydig cell generations. Human Leydig cells are irregular in outline, deeply staining with basophilic dyes and exhibit a characteristic circular or ovoid nucleus. The density of their cytoplasm is attributed to extensive domains of smooth endoplasmic reticulum, characteristic of steroidogenic tissue. Mitochondria are numerous and lipid droplets and lipfuscin inclusions accumulate with advancing age. Crystals of Reinke up to 30 microns in length are often noted in the Leydig cell cytoplasm although their function remains unknown. The intertubular tissue contains small calibre lymphatic vessels, fibroblasts, collagen, blood vessels and occasional macrophages. With increasing age, declining sperm production and lowered androgen levels are correlated with decreases in the numbers of Sertoli cells and Leydig cells although the mechanisms responsible for this attrition have not been defined. Continued collaboration between morphologists and physiologists is necessary if we are to understand fully the endocrine regulation of spermatogenesis and the factors contributing to disturbances of spermatogenic function. PMID- 1616445 TI - The prenatal and postnatal development of the testis. PMID- 1616446 TI - The Sertoli cell. PMID- 1616447 TI - Local control systems within the testis. AB - A number of physiological and pathological observations cannot readily be explained unless one accepts that there exists within the testis some sort of local control system. This local network of regulatory interactions offers not only an additional level of fine regulation for individual testicular functions, but also creates an opportunity for co-ordination and integration of distinct activities such as germ cell development and androgen production. There is an overwhelming amount of data indicating that the testis produces a variety of regulatory molecules and that many of these agonists have marked effects on the function of testicular cells in vitro. Some of these molecules are identical with or are at least related to known hormonal and humoral agonists. Others are novel and require further characterization. The exact cellular origin of many of these regulatory factors remains unknown. This overview has been limited to regulatory interactions between somatic testicular cells. Particular attention has been paid to communications between the interstitial and the tubular compartment. It should be evident that the nature and the significance of these interactions is only beginning to emerge. The major difficulty remains to distinguish effects that are restricted to the specific and often artificial conditions of in vitro systems from phenomena that are relevant to testicular control in vivo. Further progress in this field will rely on the development of appropriate systems to study local interactions in vivo. Valuable attempts have been made in this direction: vitamin A induced synchronization of spermatogenesis may offer a model to study stage dependent alterations in the interstitial compartment (Morales and Griswold, 1987; Bartlett et al, 1989); destruction of Leydig cells followed by substitution with androgens might clarify the role of non-steroidal Leydig cell mediators on tubular function (Shape et al, 1988). Up to now these approaches have failed to demonstrate an important role for local regulatory interactions. It is obvious that both models are relatively crude, however, and that subtle changes may have been missed under the experimental conditions used. It should be stressed that some of the observed complexities may be inherent to local regulatory networks. In fact, such networks tend to display a certain level of redundancy. It is evident, for example, that a number of locally produced mediators can also reach the testis via the circulation. In this setting the relative contribution of circulating and locally produced factors may vary depending on developmental stages, physiological or pathological conditions. A relative redundancy may exist for distinct locally produced mediators.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1616449 TI - The physiology of testicular inhibin and related proteins. AB - The roles of inhibin and related proteins in the male remain unclear, although it is becoming increasingly evident that they play a part in FSH regulation and testicular function, including spermatogenesis. The difficulties associated with these questions have been the limited availability of inhibin and related proteins for in vivo studies, the absence of specific assay methods, and the unclear relationship of inhibin and testosterone in the regulation of FSH secretion. With the availability of human recombinant preparations and the current development of new assays, it is anticipated that many of these questions will be resolved. PMID- 1616448 TI - Control of spermatogenesis by follicle stimulating hormone and testosterone. PMID- 1616450 TI - Testicular steroidogenesis and androgen use and abuse. AB - The possibility of widespread use of androgens in the normal male population for the promotion of growth, sexual dysfunction, contraception, osteoporosis and ageing and large scale abuse by athletes have propelled androgen replacement out of the narrow confines of male hypogonadism and highlighted the many gaps in our knowledge. There is now a new appreciation of the much wider aetiological, therapeutic, preventative and public health implications surrounding the clinical use of androgens. To realize the many potential health benefits through manipulations of the androgen milieu of normal men, basic and clinical investigations into a number of key unresolved issues are urgently required. There is a need to understand the molecular mechanisms underlying the differential roles of testosterone, DHT and oestradiol in various androgen responsive target tissues especially with reference to the pathogenesis of prostatic hyperplasia or carcinoma. It is also necessary to define the dose response relationships of the action of androgens on spermatogenesis (and basis for inter-ethnic differences), sexual and aggressive behaviour and bone mineral turnover over a wide dose range. Clinically, it is important to systematically assess whether there is any increased risk for cardiovascular and prostatic diseases in androgen replacement and the risk-benefit issues concerning androgen therapy in aged men. Development of androgens with high therapeutic indices, long half-lives, zero-order release kinetics and perhaps selective target tissue specificity through modification to the steroid structure can further optimize future modalities of androgen therapy. PMID- 1616451 TI - Evaluation of testicular function. AB - The evaluation of testicular function is based primarily on a detailed medical history, a careful physical examination, basal measurements of FSH, LH and testosterone and a routine semen analysis. In a patient with androgen deficiency, the diagnosis can often be made with these basic tests. The clinician will then decide on other investigations to localize the organic lesion and to plan further treatment for the patient. Sperm function tests are often performed in patients presenting with infertility. These newer tests may help to delineate the abnormality of the spermatozoa at each stage during the achievement of fertilizing capacity such as adequate forward motility, penetration of cervical mucus, acrosome reaction, development of hyperactivated motility, binding to the zona pellucida, and fusion with the oocyte. Currently, many of these sperm function tests depend on cumbersome bioassays with many limiting factors contributing to their availability, accuracy and precision. The development of biochemical tests as markers of sperm function may allow more precise definition of sperm functional abnormalities. With the continued improvement of computer aided sperm analysis, objective motion parameter measurements are possible and morphological assessment are being developed. These newer objective methods of semen analysis have to be shown to be valuable in the clinical assessment of patients with testicular dysfunction. PMID- 1616452 TI - An approach to the management of male infertility. AB - Male factors are present in nearly half the couples consulting for infertility. The correct approach to the management of male infertility follows a logical and scientifically sound sequence of procedures. These include history taking, systematic physical examination for general and local causes of abnormal semen quality, complemented by contact-thermoscopy, echography and hormone assays if available. Conventional semen analysis can be replaced by more accurate advanced methods measuring sperm motility characteristics. Several tests of sperm functional capacity are also available. It is mandatory to detect and treat known and accepted causes of impaired sperm quality using adequate and reliable methods. Complementary methods to stimulate spermatogenesis, or to assist reproduction should be offered in well-defined cases. The overall success rate of male infertility treatment remains lower than that of female treatment, though recent technology has improved results remarkably. PMID- 1616453 TI - Effects of transections to the vomeronasal nerves or to the main olfactory bulbs on the initiation and long-term retention of maternal behavior in primiparous rats. AB - While the onset of maternal behavior at parturition is mediated by hormones, the maintenance of maternal behavior during the first few postpartum weeks depends on experiences acquired while the dam interacts with pups (Rosenblatt, 1990). In fact, if female rats are permitted as little as 2 h or maternal experience within 36 h after Cesarean delivery, they exhibit heightened maternal behavior during maternal induction tests 10 days later; in contrast, dams separated from young at the time of Cesarean delivery and not permitted a maternal experience fail to respond maternally in tests 10 days later (Orpen & Fleming, 1987). In this study we investigated the role of chemosensory input through the vomeronasal and main olfactory systems in this maternal experience effect. Six groups of primiparous females were tested for maternal behavior to foster pups presented 9-10 days after Cesarean delivery: three groups were permitted to interact with pups for a 2-h period 36 h after Cesarean delivery; and three groups were separated from pups until testing and were given no maternal experience. Within each experience condition, one group sustained bilateral section of the vomeronasal nerves, one sustained bilateral coronal cuts through the midsection of the main olfactory bulbs, and one group sustained small medial olfactory bulb cuts. The results showed that animals sustaining vomeronasal or olfactory transections, regardless of experience condition, exhibited significantly reduced latencies to maternal behavior in maternal induction tests. However, these chemosensory disruptions did not prevent an additional facilitation of maternal behavior produced by a prior maternal experience. PMID- 1616454 TI - Multitrial inhibitory avoidance learning in the crab Chasmagnathus. AB - Chasmagnathus crabs placed in the dark compartment (DC) of a double-chamber device and given electrical shocks whenever they entered or remained in the light compartment (LC), showed an LC-avoidance behavior when tested 24 h after a training session of three 30-min periods with 60-min intervals. The avoidance behavior depended neither on the shock number nor on the distribution at training but only on exposure to the LC-shock contingency, thus suggesting that crabs learn to associate the LC with an aversive situation. The learning outcome disclosed a higher degree of refraining from entering the LC rather than a faster escaping to the DC. Distributed practice proved more effective on crab avoidance learning than massive practice. Retention of the learned behavior occurred after a 24-h rest interval in an environment different from that of the training apparatus. Experimental devices previously used in avoidance learning studies with crabs were improved here by automating both the computation of latency values and the event recording. PMID- 1616455 TI - Genetic analysis of isolation-induced aggression. I. Comparison between closely related inbred mouse strains. AB - Young adult males of the inbred mouse strains BALB/c, C57BL/6, CBA, C3H/He, and the outbred strain NMRI showed significant interstrain differences for isolation induced aggression as measured in a standard-opponent test. Additionally, four related inbred strains of common origin (ABG, AB//Halle, ABB, AB//Jena) were studied. ABG and AB//Halle showed nearly no overlap for the trait isolation induced aggression. Tests of histocompatibility and coat color, as well as mandible measurements, confirmed a close genetic relationship between ABG and AB//Halle. The large difference for isolation-induced aggression between these two closely related strains offers excellent opportunities to search for single gene correlates of aggression. PMID- 1616456 TI - Age-dependent changes in olfactory-mediated behavioral investigations in the male rat. AB - In the present experiment male Sprague-Dawley rats at three different ages (young, middle-aged, and old) were tested in a series of olfactory-mediated behavioral tests. The amount of ano-genital investigation directed to receptive females by old rats was significantly reduced compared to that of young and middle-aged animals. In contrast, general body investigation of receptive females was similar among the three age groups. The amount of anogenital investigation directed to nonreceptive females or immature male rats indicated significant differences only between young and old rats, with values from middle-aged rats being intermediate and not significantly different from either of the two extreme groups. General body investigation of nonreceptive females and immature males did not differ among the three age groups. Old rats showed the best performance in a location of buried food test with latencies to locate food approximately one-half that obtained from young and middle-aged rats. Measures of general locomotor activity indicated significantly greater values from young compared to middle aged and old rats, with the latter two showing very similar levels. These results demonstrate clear discriminatory differences in olfactory-mediated behavioral performance of the male rat as a function of the specific test and age of the animal. Overall, the results suggest that olfactory-mediated behaviors related to reproduction appear more sensitive to age-related declines, while behavior related to food procurement is more minimally affected. PMID- 1616457 TI - Learning of rats under amnesia caused by pentobarbital. AB - Dissociated learning of rats in the normal state and the state of amnesia produced by pentobarbital (15 mg/kg, ip) was carried out. Rats were trained to approach a shelf where they received food reinforcement. In Group 1 the rats were trained under the influence of pentobarbital to run to the same shelf as in the normal state. In Group 2 the rats were trained to approach different shelves in different drug states. It was shown that memory dissociation occurred in both groups. Differences in the parameters of training under the influence of pentobarbital between Groups 1 and 2 were revealed. These findings show that the brain-dissociated state induced by pentobarbital is formed with the participation of the mechanisms of information perception. PMID- 1616458 TI - A threshold for the protective effect of over-reinforced passive avoidance against scopolamine-induced amnesia. AB - Acetylcholine-receptor blockers produce amnesia of aversively motivated behaviors. However, when animals are submitted to relatively high intensities of footshock (over-reinforcement), anticholinergic treatment does not induce memory impairments. The aim of this work was to determine whether the antiamnesic effect produced by increasing the magnitude of the negative reinforcer is gradually established or if a threshold should be reached to obtain such an effect. Wistar rats were trained in passive avoidance using 2.5, 2.6, 2.7, 2.8, 2.9 or 3.0 mA; 5 min after training they were given one systemic injection of scopolamine (8 mg/kg). An amnesic state was produced in the groups that were trained with the lower intensities (2.5-2.7 mA); with the three higher intensities near-perfect retention was evident. These results suggest that acetylcholine is critically involved in memory consolidation, and that by increasing the magnitude of the negative reinforcer, a threshold is reached where cholinergic activity of the nervous system is not necessary for the development of the consolidation process. PMID- 1616459 TI - Nifedipine blocks retention of a visual discrimination task in chicks. AB - Reports that the dihydropyridine Ca2+ channel antagonists may facilitate memory led to the present study of the behavioral effects of nifedipine. Ninety-two 4 day-old male chicks received 0, 100 nM, 100 microM, or 10 mM nifedipine. Drugs were administered in volumes of 2 microliters into the fourth cerebral ventricle 5 min before training on a visual discrimination task. Nifedipine did not produce any detectable changes in behavior during acquisition trials. Retention, however, was impaired 24 h after training in the 100 nM and 100 microM nifedipine-treated chicks, which made significantly more errors than controls. Nifedipine did not affect the amount of time required to complete the task. No effects on body weight gain were detected, suggesting that the memory impairment was not due to a change in feeding behavior. These data are discussed in terms of the role of calcium-dependent processes in memory. PMID- 1616460 TI - Genetic Tobit factor analysis: quantitative genetic modeling with censored data. AB - Parameters of quantitative genetic models have traditionally been estimated by either algebraic manipulation of familial correlations (or familial mean squares), biometric model fitting, or multiple-group covariance structure analysis. With few exceptions, researchers who have used these methods for the analysis of twin data have assumed that their data were multinormal and, consequently, have used normal-theory estimation methods. It is shown that normal theory methods produce biased genetic and environmental parameter estimates when data are censored. Specifically, with censored data, (1) normal-theory estimates of narrow-sense heritability are either positively or negatively biased, whereas (2) estimates of shared-familial environmental variance are always biased downward. An alternative method for estimating genetic and environmental parameters from censored twin data is proposed. The method is called genetic Tobit factor analysis (GTFA) and is an extension of the Tobit factor analysis model developed by Muthen (Br. J. Math. Stat. Psychol. 42, 241-250, 1989). Using a Monte Carlo design, the performance of GTFA is compared to traditional quantitative genetic methods in both large and small data sets. The results of this study suggest that GTFA is the preferred method for the genetic modeling of censored data obtained from twins. PMID- 1616461 TI - The analysis of parental ratings of children's behavior using LISREL. AB - A common procedure for assessing children's behavior is to obtain parental ratings of the child. Since the ratings obtained are a function of both parent and child, disentangling the child's phenotype from that of the rater becomes an important methodological problem. For the analysis of genetic and environmental contributions to children's behavior, solutions to this are available when multiple raters, e.g., two parents, rate multiple children, e.g., twins. This paper describes and illustrates simple LISREL models for the analysis of parental ratings of children's behavior. We show how the assumption that mothers and fathers are rating the same behavior in children can be contrasted with the weaker alternative that parents are rating correlated behaviors. Given the stronger assumption, which appears adequate for ratings of children's internalizing behavior problems, the contribution of rater bias and unreliability may be separated from the shared and nonshared environmental components of variation in a behavior genetic analysis. PMID- 1616462 TI - Decomposition of multivariate phenotypic means in multigroup genetic covariance structure analysis. AB - Observed differences in phenotypic means between groups such as parents and their offspring or male and female twins can be decomposed into genetic and environmental components. The decomposition is based on the assumption that the difference in phenotypic means is due to a difference in the location of the normal genetic and environmental distributions underlying the phenotypic individual differences. Differences between the groups in variance can be accommodated insofar as they are due to differences in unique variance or can be modeled using a scale parameter. The decomposition may be carried out in the standard analysis of genetic covariance structure using, for instance, LISREL. Illustrations are given using simulated data and twin data relating to blood pressure. Other possible applications are mentioned. PMID- 1616463 TI - Evidence for a genetic etiology in hyperactivity in children. AB - There has been considerable controversy over the nosology of hyperactivity and attention deficit hyperactivity disorder (ADHD). There have been suggestions that genetic influences may play a role in the origins of individual differences on this dimension or dimensions of behavior and that an understanding of the significance of genetic factors might help to clarify the classification of these disorders. Multiple regression is used to analyze data from a sample of 91 pairs of identical twins and 105 pairs of same sex fraternal twins. The heritability of extreme group membership (h2g = 0.75) was significant for activity rated by the mother. The heritability for one of the measures of attention deficit was also significant (h2g = 0.76). The results are consistent with a significant genetic contribution to individual differences in activity levels and attention abilities. PMID- 1616464 TI - Seven generations of genetic selection for ethanol dependence in mice. AB - An animal model of alcohol dependence is being produced by selecting mice for differences in severity of ethanol withdrawal seizures. Replicate lines of high dependence (HA), low-dependence (LA), and control (CA) mice are being developed by within-family selection. After seven generations both (replicate) HA and LA lines have separated significantly. Some of the difference between the replicate pairs of HA and LA in the early generations was due to differences in ethanol consumption. This difference in consumption may be attributable to a difference in metabolic rate or activity level rather than to a difference in ethanol preference. Females are more susceptible to seizures than males; this appears to be due partly to their higher consumption of ethanol during treatment. PMID- 1616465 TI - Genetics of spike-wave discharges in the electroencephalogram (EEG) of the WAG/Rij inbred rat strain: a classical mendelian crossbreeding study. AB - The WAG inbred strain might be an animal model for human absence epilepsy. To study the inheritance pattern of absence epilepsy, WAG rats were crossbred, in a classical Mendelian way, with inbred ACI rats which show no signs of epilepsy. In the parental strains, reciprocal F1 hybrids, F2, B1, and B2 generations, the number and duration of spike-wave discharges were determined. One hundred percent of the F1 animals showed spike-wave discharges, while the percentages for the F2, B1, and B2 generations were 79, 95, and 37%, respectively. These results suggest that the occurrence of spike-wave discharges is determined by one gene with a dominant mode of inheritance. Cavalli's least-squares fitting procedure suggested different genetic models for the two parameters (number and duration) during the two periods (dark and light). These results confirm our previous findings (Peeters et al., Behav. Genet. 20, 453-460, 1990) that a number of genes are involved in absence epilepsy. One dominant gene appears to determine the occurrence, however, while others manipulate the number and duration of epileptic phenomena during the two periods dark and light. PMID- 1616466 TI - Behavioral coupling in tettigoniid hybrids (Orthoptera). AB - Studies of the mating behavior of male and female F1 hybrids between closely related taxa can provide information concerning the genetic control of characters that play a major role in speciation. Orthoptera have been used previously for such studies. Hybrid crickets show behaviors which are broadly intermediate to the parentals but hybrid grasshoppers may retain parental behavior patterns. This study examines the behavior of hybrid Ephippiger ephippiger bushcrickets, the third major orthopteran group. The differences in male song and female preference are probably both mainly additive and male song differences not sex linked. Thus, given a choice, hybrid females would prefer to mate with hybrid males, an example of "behavioral coupling." The evolutionary inferences which can be drawn from studies of F1 hybrids between closely related taxa are discussed. PMID- 1616467 TI - Heterosis for concentrations of dopamine, norepinephrine, their metabolites, and epinephrine in the chick hyperstriatum ventrale, hypothalamus, and optic tectum. AB - A complete diallel cross using both sexes was derived from four parental populations of chickens having divergent developmental rates. This paradigm was used to investigate the genetic architecture of the neurochemicals, norepinephrine (NE), epinephrine (EPI), 3,4-dihydroxyphenylacetic acid (DOPAC), dopamine (DA), and 3-methoxy-4-hydroxyphenylglycol (MHPG). No sex differences were found for any genetic parameter investigated. Estimates of average line effects, maternal effects, and additive sex linkage were not significant. Highly significant heterosis, in the form of overdominance, was observed for catecholamine and metabolite concentrations. Hybrids exhibited significant line heterosis in the positive direction for NE, while heterosis for MHPG was observed in the negative direction for all crosses. Heterosis for EPI was both line and brain area specific with the hypothalamus showing greatest heterotic effects. DOPAC showed significant heterosis for all lines only in the optic tectum, and DA showed little heterosis specific to any line, cross, or brain area. PMID- 1616468 TI - Parental divorce and adolescent maladjustment: scientific inquiry vs public information. PMID- 1616469 TI - Cardiophobia: a paradigmatic behavioural model of heart-focused anxiety and non anginal chest pain. AB - Cardiophobia is defined as an anxiety disorder of persons characterized by repeated complaints of chest pain, heart palpitations, and other somatic sensations accompanied by fears of having a heart attack and of dying. Persons with cardiophobia focus attention on their heart when experiencing stress and arousal, perceive its function in a phobic manner, and continue to believe that they suffer from an organic heart problem despite repeated negative medical tests. In order to reduce anxiety, they seek continuous reassurance, make excessive use of medical facilities, and avoid activities believed to elicit symptoms. The relationship of cardiophobia to illness phobia, health anxiety, and panic disorder is discussed. An integrative psychobiological model of cardiophobia is presented which includes previous learning conditions relating to experiences of separation and cardiac disease; deficient and inappropriate behavioural repertoires which constitute a psychological vulnerability for cardiophobic problems; negative life events, stressors, and conflicts in the person's present situation that trigger and contribute to the symptoms; current affective, cognitive, and behavioural symptoms and their stimulus properties; and genetic and acquired biological vulnerability factors. Finally, recommendations for the treatment of cardiophobia are derived from the model and areas of future research are outlined. PMID- 1616470 TI - The many faces of Pan: psychological and physiological differences among three types of panic attacks. AB - The thesis of this paper is that failure to recognize the psychological and physiological differences among panic attacks within DSM-IIIR precludes meaningful comparisons and evaluations of research findings, confounds theoretical issues, and impairs the development of more specific, and thereby more effective, programs of treatment. To remedy this, a recommendation is made to define panic attacks on the basis of psychological and physiological distinctions that fit three categories of severity: Type I (classic panic attack), Type II (anticipatory panic attack), and Type III (cognitive panic attack). The logical-empirical rationale for the categories recommended is presented in the context of relevant research findings. Implications for theory, experimental design, and treatment are discussed. PMID- 1616471 TI - Adolescent dental fear and control: prevalence and theoretical implications. AB - This study examined the prevalence and etiology of dental fear in a large, representative sample of Singapore adolescents. Participants completed a questionnaire regarding fear of the dentist, dental beliefs and their most recent dental visit. The population prevalence of high dental fear was 115 fearful children per 1000 population (SE = 0.02). Children who reported painful treatment and perceived lack of control at the dentist were 13.7 times more likely to report high fear and 15.9 times less likely to be willing to return to the dentist or dental nurse. The etiology of severe clinical fear appears strongly related to direct conditioning in the presence of pain and vulnerability. PMID- 1616472 TI - Site-specific muscle hyper-reactivity in musicians with occupational upper limb pain. AB - Fourteen musicians who reported a history of pain in the upper limb associated with the playing of their instruments were compared with a sample of pain-free musicians, matched for age, sex and musical instrument. Four tasks were presented in random order and included neutral, general stressor, personal stressor and pain stressor tasks. Ratings of stressfulness and recordings of skin conductance level confirmed the effectiveness of the experimental manipulations for both subject groups. No differences were found between groups or tasks for frontalis surface electromyograph (EMG) activity. Evidence was found, however, of EMG elevation in flexor and trapezius muscles on the pain side for the pain subjects, in response to the task involving recall of a pain experience. This elevation was not found for the pain-free controls or for other stressor tasks, although some elevation in response to the pain stressor task was found for pain subjects in the trapezius muscles of the non-pain side. The duration of return to baseline of EMG following the pain stressor task was found to be extended in pain subjects for the trapezius, but not for the flexor muscles of the pain side. The findings suggest that site-specific muscle hyper-reactivity may play a role in the development and maintenance of occupational upper limb pain in musicians. PMID- 1616473 TI - Origins of fear of dogs in adults and children: the role of conditioning processes and prior familiarity with dogs. AB - One hundred adults and 30 children completed questionnaires to investigate fear of dogs. Dog fearful adults asked to recall the origins of their fear reported classical conditioning experiences more frequently than vicarious acquisition or informational transmission. Overall, however, there was no difference in the frequency of attacks reported by the fearful and non-fearful groups. Significantly more fearful than non-fearful adults reported little contact with dogs prior to the onset of their fear which suggests that early non-eventful exposure to dogs may prevent a conditioning event from producing a dog phobia. Most adults reported that their fear began in childhood, and dog fear were more frequently reported by children than by adults. In the aggregate, however, dog fearful adults and children differed in several ways; children were more likely than adults to report having received warnings about dogs, but also to recognize the potential attractiveness of a friendly dog. Unlike dog-fearful children, dog fearful adults reported many other fears in addition to their fear of dogs. A better understanding of fear of dogs in adults may depend on discovering why some dog-fearful children, but not others, apparently lose their fear of dogs as they become older. PMID- 1616474 TI - General and specific fears in referred and self-referred adult patients with extreme dental anxiety. AB - The levels of, and relationships between, dental fear and general fears and phobias were studied in 109 adult patients at a specialized dental fear clinic using two dental fear scales (the Dental Anxiety Scale and the Dental Fear Survey) together with the Fear Survey Schedule II (FSS-II) and some additional fear items. Referred and self-referred fearful dental patients answered mailed questionnaires in conjunction to being put on a 1 yr waiting list for treatment. Among feared objects and situations the separate item 'pain' revealed the highest mean scores for both men and women, followed by fear of suffocating, death of a loved one and sharp objects among women, and death of a loved one, suffocating and hypodermic needles among men. With few exceptions, women scored higher than men. The frequencies of extreme fears (6 and 7 on a 7-point scale) were high and 92.7% of the patients reported at least one extreme fear. Half of the subjects (49.5%) reported five fears or more. It was also shown that a number of FSS-II items correlated to dental fear indicating a relationship between general and dental fear. These results indicated that a large proportion of these dentally fearful individuals were prone to fear-associated reactions and behaviors, which has previously been shown to negatively influence the prognosis of treatment. PMID- 1616475 TI - Panic disorder in the families of patients with normal coronary arteries and non fear panic disorder. AB - Patients with non-fear panic disorder (NFPD) meet DSM-III-R criteria for panic disorder, but do not report subjective fear or anxiety. Although apparently common in medical settings, this controversial group is in need of further diagnostic validation. This study assessed family history of panic disorder in patients with chest pain and normal coronary arteries (CP/NCA) and either NFPD, panic disorder with fear, or no panic. It was hypothesized that the two panic disorder groups would have similar, elevated rates of panic disorder in their first-degree relatives, compared to patients without panic. The results support the hypothesis; about 17% of the first-degree relatives of both NFPD and panic disorder patients were diagnosable with panic disorder according to proband interviews, whereas only 4.6% of the first-degree relatives of patients without panic were so diagnosable. These results support the diagnostic validity of NFPD in CP/NCA patients, because such patients had a family history of panic disorder similar to patients with a more classical panic disorder presentation. The lack of fear symptoms and behavior in NFPD may cause panic disorder to be overlooked as a potential cause of somatic symptoms in patients with no medical explanation for their condition. PMID- 1616476 TI - Is pain sensitivity associated with occupational fears in police recruits? AB - Gross (Behaviour Research and Therapy, 30, 7-13, 1992a) showed that the fear of pain (pain sensitivity) could be distinguished from dental fears and health concerns. Furthermore, the Pain Sensitivity Index (PSI) correlated significantly with pain expectations, and pain expectations correlated significantly with dental avoidance behaviour. However, Gross noted that the psychometric properties of the PSI had not been fully determined. The present study examined the factor structure of an expanded version of the PSI with a sample of 212 police recruits. A single factor accounted for 52.1% of the variance and the reliability coefficient (alpha = 0.89) indicates that the PSI possesses a high degree of internal reliability. Subsequently, it was hypothesized that pain sensitivity correlates positively with fears relating to police tasks which are characterized by pain expectancies, such as the fear of being assaulted during operational police work. In support of the hypothesis, pain sensitivity correlated highest with situations involving pain. The pain sensitivity construct may help to explain individual differences in fear reactions to situations where pain could be experienced, such as operational police duties or dental attendances. PMID- 1616477 TI - Do men lie on fear surveys? AB - The likelihood that males equivocate in their ratings of common fears was evaluated. A fear survey was given to 30 female and 26 male college students in a classroom setting. A second fear survey which contained duplicate items from the first was administered to the same students in a laboratory setting prior to watching videotaped scenes of fish, rats, mice and a shorter roller coaster ride. Before the second survey was given, the students received instructions which implied that their truthfulness could be independently evaluated through changes in their heart rate while they watched the videotape. Changes in the averaged fear ratings for the three high-fear items shown in the videotaped scenes were compared between males and females across the two survey conditions. Males' ratings of rats, mice, and roller coasters increased markedly from the first survey to the second, while fear ratings by females did not change. These results are consistent with the idea that the expression of fear by men is affected by conformation to the traditional male gender role. PMID- 1616478 TI - Biochemical genetics of alcohol dehydrogenase isozymes in the gray short-tailed opossum (Monodelphis domestica). AB - Polyacrylamide gel-isoelectric focusing (PAGE-IEF) methods were used to examine the multiplicity, tissue distribution, and biochemical genetics of alcohol dehydrogenase (ADH) isozymes among gray short-tailed opossums (Monodelphis domestica). Seven ADH isozymes were resolved and distinguished on the basis of their isoelectric points, tissue distributions, and substrate and inhibitor specificities. ADH1 and ADH2 exhibited Class I properties and were observed in liver (and intestine) extracts. ADH3, ADH4, and ADH5 showed "high-Km" (possibly Class IV) properties, with ADH3 and ADH4 exhibiting high activity in cornea, ear, stomach, and esophagus extracts. ADH6 and ADH7 exhibited Class III properties, including activities as formaldehyde dehydrogenases, with each showing different tissue distribution characteristics; ADH6 was widely distributed, and ADH7 was restricted to prostate extracts. An additional form of formaldehyde dehydrogenase (FDH) was observed, which was inactive with hexenol and ethanol as substrates. Isoelectric point variants were observed for ADH3 (three forms) and for ADH4 (two forms), and the inheritance of ADH3 was studied in 15 families of M. domestica. The data were consistent with codominant inheritance of two alleles (ADH3*A and ADH3*B) at a single autosomal locus (designated ADH3) and with a model involving a dimeric ADH isozyme: ADH3 (gamma 2 isozyme, forming three dimers designated gamma 1(2), gamma 1 gamma 2, and gamma 2(2) in heterozygous individuals). PMID- 1616479 TI - Expression and distribution of cytosolic 6-phosphogluconate dehydrogenase isozymes in maize. AB - Maize (Zea mays L.) cytosolic 6-phosphogluconate dehydrogenase isozymes (EC 1.1.1.44; 6-PGD) are encoded by unlinked loci Pgd1 and Pgd2. Two families from a Robertson's Mutator line were isolated which have no detectable expression of Pgd2. These Pgd2-null mutants and a Pgd1-null line were used to generate plants homozygous for null alleles at both cytosolic 6-PGD loci. The specific activity of 6-PGD in the double-null mutant was between 20 and 30% of wild-type levels in root extracts. The double-null mutant was reproductively viable in a moderate environment, suggesting that wild-type levels of cytosolic 6-PGD activity are not essential for growth. Isozyme dimer ratios in roots, leaves, and scutellum were binomial and reflected the wild-type gene copy number. 6-PGD isozymes showed tissue- and cell type-specific expression. PMID- 1616480 TI - Peptidase B polymorphism in cattle erythrocytes. AB - Starch gel electrophoresis and histochemical staining with L-leucylglycyl-glycine revealed genetic polymorphism in peptidase B in cattle erythrocytes. Genetic analysis of 164 full families indicated that the three phenotypes observed are the product of an autosomal locus with two codominant alleles, PepB1 and PepB2. A sample consisting of 2630 individuals representing 5 Zebu, 13 European, and 2 crossbred breeds was studied. This polymorphism was observed in all Zebu and crossbred breeds. The frequency of the PepB1 allele was 0.89, 0.83, 0.59, 0.82 and 0.62 in the Nellore, Gyr, Guzerat, Indubrazil, and Tabapuan breeds, respectively. The PepB2 allele appears to be fixed in the European breeds, except Marchigiana and Chianina. PMID- 1616481 TI - Molecular analysis of cis-regulatory sequences at the alpha-amylase locus in Drosophila melanogaster. AB - The Amylase locus in Drosophila melanogaster contains duplicate, divergently transcribed structural genes for alpha-amylase, AmyA and AmyB. A sensitive and reliable transient expression assay was developed for testing amylase activities produced by exogenous Amy genes in somatically transformed larvae of an amylase null strain of flies. Alleles tested, AmyA and AmyB, came from recombinant clone lambda Dm65, which contains genomic DNA from a Canton-S strain. The transient assay was used in a deletion analysis aimed at locating cis-regulatory sequences within the 5' region of AmyB. Results suggest that upstream regulatory sequences for correct spatial expression of AmyA and AmyB in third-instar larvae are located within 446 and 430 bp of their respective starts for transcription. A sequence required for high levels of AmyB expression was located within its 5' upstream region between the base pairs at -332 and -219. AmyA does not appear to have a comparable regulatory element in its 5'-flanking sequence. Barely detectable expression of AmyB was observed when it was flanked by only 92 bp of upstream sequence. A model is proposed for incomplete coordinate control of the duplicate Amy genes. PMID- 1616482 TI - Variation in coding exons of two electrophoretic alleles at the pigtail macaque carbonic anhydrase I locus as determined by direct, double-stranded sequencing of polymerase chain reaction (PCR) products. AB - Two, electrophoretically distinct, forms of carbonic anhydrase I (CA Ia and CA Ib) are found at high polymorphic frequencies in red cells of natural populations of pigtail macaques, Macaca nemestrina, from southeast Asia. By use of the polymerase chain reaction, exons of the CA I gene were amplified from homozygous (a/a, b/b) and heterozygous (a/b) animals. Direct sequencing of the amplified DNA from four animals revealed differences between the a and the b electrophoretic alleles ranging from three to six nucleotides, and from one to three differences within each allele. These results indicate a greater genetic variability at the CA I locus in this macaque species than previously realized. PMID- 1616483 TI - A biochemical genetic study of alcohol dehydrogenase isozymes of the medfly, Ceratitis capitata Wied. AB - A concerted effort is under way to analyze, at the genetic, biochemical, and molecular level, the Adh gene system in the medfly Ceratitis capitata, an important agricultural pest. The isoelectric focusing (IEF) pattern of alcohol dehydrogenase (ADH) of the medfly demonstrates the presence of two well differentiated, genetically independent dimeric proteins, called ADH-1 and ADH-2. These proteins do not exhibit interlocus heterodimeric isozymes, and the genes are not controlled coordinately during development, Adh1 and Adh2 being expressed mainly in muscle or in fat body and ovary, respectively. From the intensity of the IEF isozyme patterns, primary alcohols are judged to be better substrates than secondary alcohols, in contrast with Drosophila melanogaster ADH, and ethanol is probably the most efficient substrate for both sets of isozymes. The isoelectric points of ADH-1 (pI = 5.4) and ADH-2 (pI = 8.6) are different from D. melanogaster ADH (pI = 7.6), but the medfly ADH-1 has a native molecular weight (approx. 58 kD) close to that of D. melanogaster. A population survey of samples both from laboratory strains and from wild geographically different populations showed that the Adh1 locus is more polymorphic than Adh2. The most variable populations are from Africa, the supposed source area of the species. Further, a case of selection at the Adh1 locus under laboratory conditions is reported. The hypothesis of Adh gene duplication and the degree of similarity between medfly and Drosophila ADH are also discussed. PMID- 1616484 TI - Purification and characterization of diaphorases from some Drosophila species. AB - Diaphorase-1 and diaphorase-2 were isolated from two Drosophila species, D. virilis and D. melanogaster, and purified by gel filtration, affinity chromatography, immunoaffinity chromatography, and ion-exchange chromatography. The molecular weights of both enzymes were the same in each species. The molecular weight of diaphorase-1 was the same under both denaturating and nondenaturating conditions, close to 60,000, indicating a monomeric structure. Sodium dodecyl sulfate (SDS) electrophoresis of the purified diaphorase-2 revealed the presence of a single protein band of 55,000 Da, while the molecular weight of the native enzyme was found to be 67,000. The two diaphorases were further characterized by their pH optima, isoelectric points, and kinetic parameters, and antibodies were raised in rabbits against the purified enzymes from D. virilis. The antibodies showed no cross-reactions but recognized the corresponding diaphorases in D. melanogaster and D. novamexicana as well as D. virilis. The data obtained confirmed the hypothesis of an independent genetic control of diaphorase-1 and diaphorase-2 in Drosophila. PMID- 1616485 TI - Genetic diversity at electrophoretic loci in the house fly, Musca domestica L. AB - Vertical polyacrylamide gel electrophoresis was used to separate enzyme proteins at 73 putative loci in natural house fly populations sampled in central Iowa. Thirty-nine of the loci were polymorphic (53%). The mean effective number of alleles per polymorphic locus was 1.93 and 1.47 alleles among 68 scored loci. Observed and expected heterozygosities at 34 house fly loci were 0.1628 and 0.1834, respectively. No statistically significant differentiation was detected among nine central Iowa fly populations in 1989 or among nine Iowa and three Minnesota populations in 1990. PMID- 1616486 TI - A two-base-pair substitution in T7 promoter by SP6 promoter-specific base pairs alone abolishes T7 promoter activity but reveals SP6 promoter activity. AB - The phage T7 and SP6 RNA polymerase-promoter systems are very similar in many characteristics, but maintains stringent specificity for each. In order to identify the base pair element that distinguishes between T7 and SP6 promoters, the base pairs at -12, -10, -9, and -8 of the T7 promoter consensus sequence were changed singly and multiply to the SP6 promoter-specific base pairs, and assayed for T7 and SP6 promoter activities. The results indicate that the primary discrimination element is the base pairs at -8 and -9. The two-base-pair substitution alone in T7 promoter by SP6-specific base pairs is sufficient to make the T7 variant be a SP6 promoter, abolishing T7 promoter activity. PMID- 1616487 TI - Isolation of a crotalase-like protease with alpha-fibrinogenase activity from the western diamondback rattlesnake, Crotalus atrox. AB - Venom toxins were isolated from rattlesnake (Crotalus atrox) venom by cation exchange chromatography. Seven major fractions could be obtained by single-step ion-exchange chromatography with two fractions showing essentially apparent homogeneity by SDS-gel electrophoresis. All fractions showed various extents of specific proteolytic activity against alpha- or beta-chains of fibrinogen molecules. Further characterization of one of the purified fractions with alpha fribrinogenase activity indicated that it is a single-chain thrombin-like protease with a molecular mass of about 30 kDa. It is relatively heat stable, inhibited by phenylmethanesulfonyl fluoride, N alpha-p-tosyl-L-phenylalanine chloromethyl ketone and N alpha-p-tosyl-L-lysine chloromethyl ketone but not by soybean trypsin inhibitor and beta-mercaptoethanol. Amino acid analysis showed that the enzyme possesses an amino acid composition very similar to thrombin and crotalase characterized before from the closely related snake venoms. N-Terminal sequence analysis of the enzyme corroborated the close similarity between this enzyme and those sequences of crotalase and kallikrein-like enzymes characterized from the same Crotalidae snake family. This study is in contrast to the previous reports which indicated a lack of thrombin- and crotalase-like enzyme in the venom of Western diamondback rattlesnake. PMID- 1616488 TI - Characterization of superoxide dismutase from south Indian scorpion venom. AB - A manganese containing superoxide dismutase was purified to homogeneity from the venom of scorpion Heterometrus fulvipes by ammonium sulfate fractionation followed by gel filtration on Sephadex G-100 and ion exchange chromatography on DEAE-cellulose. The enzyme has a molecular weight of 100,000. Optimum pH for enzyme activity was 8.5 and optimum temperature was 45 degrees C. The enzyme was not sensitive to either cyanide or hydrogen peroxide but was inhibited by chloroform-ethanol mixture and p-hydroxymercuribenzoate. Metal chelators, EDTA, o phenanthroline and diethyldithiocarbamate inhibited the enzyme activity in decreasing order. The effect of 6 M urea, sodium dodecylsulfate, guanidinium chloride and nitroprusside on enzyme activity has been studied. An antiserum raised against H. fulvipes venom inhibited the superoxide dismutase activity. PMID- 1616489 TI - Glutathione S-transferase isozymes in rat lens. AB - Rat lens contains two classes of glutathione S-transferase (GST) isozymes; one is class mu, Yb1-Yb1, and the other is class pi, Yp-Yp, judged from their molecular weights, immunological properties and N-terminal amino acid sequences. The expression pattern of GST isozymes in the rat lens is different from that in pig and bovine lenses which have only class pi and class mu isozymes, respectively. PMID- 1616490 TI - Studies on oxalate oxidase from beet stems upon immobilization on concanavalin A. AB - Oxalate oxidase (EC 1.2.3.4) was purified from beet stems and immobilized on concanavalin A. The bound enzyme showed a high resistance of denaturation and increased the storage stability at 4 degrees C. The immobilized oxidase showed a broad optimum at pH 3.5-5, compared to the free enzyme with a sharp optimum at pH 4.5. There was a 3-fold increase in the apparent Km value on immobilization. The lectin interaction also eliminated the inhibitory effect produced on the enzyme by azide, nitrate and glycollate. The stimulatory effect on the enzyme activity by the flavins was not seen with the bound enzyme. The interaction of oxidase on concanavalin A-Sepharose 4B column and its reversal with methyl alpha-D mannoside, indicated the presence of polysaccharides. The glycoprotein nature was further confirmed by periodic acid-sciff staining procedure of the enzyme after gel electrophoresis. PMID- 1616491 TI - Transcript RNA having trans-acting antitermination activity on the T7 transcription terminator. AB - The efficiency of the phage T7 intrinsic terminator was determined in pulse labeling in vitro transcription reactions. While the factor-independent terminator subcloned in pET3a showed consistently high (approximately 80%) efficiency, the efficiency of the same terminator in pGEM3ZT was initially approximately 60% but exponentially decreased to approximately 20%, although the 39-bp terminator, and its 73-bp upstream and 32-bp downstream sequences are identical in the two plasmids. When transcription product mixture of pGEM3ZT was added to an on-going reaction of pET3a, the terminator efficiency from pET3a was immediately reduced to approximately 40%. Furthermore, when the pGEM3ZT product mixture was subjected to the promoter-cleaving HinfI digestion and then phenol/chloroform extraction, the mixture still maintained the trans-acting antitermination activity. The results suggest that the trans-acting component(s) are RNA synthesized from pGEM3ZT. PMID- 1616492 TI - Impact of chronic phosalone toxicity on Bohr factor and oxygen equilibrium curves of rat. AB - The multiple sublethal doses of phosalone induced changes in haemodynamics, maximum absorption spectra, oxygen equilibrium curves (OEC), half saturation tension (P50), degree of interaction (n), pH of blood, Bohr factor and circulatory gases of blood in rat, Rattus norvegicus. The results have obviously shown that increase the activation of pyridoxal phosphate, shift of OEC to right and decrease in the affinity of haemoglobin for oxygen at tissue level. PMID- 1616493 TI - Peroxidative crosslinking of myosins. AB - The effect of myoglobin, free hemin and H2O2 on myosins from heart and skeletal muscle was studied. SDS-gel electrophoresis revealed that each agent caused intermolecular thiol crosslinking of both myosins dissociable by excess of beta mercaptoethanol. In the simultaneous presence of H2O2 and myoglobin or H2O2 and free hemin, myosin formed covalent aggregates undissociable by beta mercaptoethanol and therefore assessed to formation of non S-S inter molecular covalent bonds. The latter aggregates are suggested to result from pairing of myosin radicals formed by the H2O2 induced ferryl iron state in myoglobin, free hemin or hemo-myosin. PMID- 1616494 TI - Changes in protein and nonprotein thiol contents in bladder, kidney and liver of mice by the pesticide sodium-o-phenylphenol and their possible role in cellular toxicity. AB - Acute treatment of mice with Na-o-phenylphenol or phenylbenzoquinone, an electrophilic metabolite of o-phenylphenol, resulted in differential depletion of contents of protein and nonprotein thiols in bladder, kidney and liver. Maximum decrease in the levels of protein and nonprotein reduced thiols was observed in bladder (by both agents) and was followed by kidney (by both agents) and liver (phenylbenzoquinone only). The reason for this differential changes in reduced thiol contents remains to be understood. The content of protein and nonprotein disulfides was higher in bladder of mice treated with Na-o-phenylphenol compared to that observed in untreated mice bladder. Phenyl 2,5'-p-benzoquinone mediated in vivo depletion of nonprotein and protein thiols suggests that Na-o phenylphenol treatment may decrease in vivo thiols via the formation of phenylbenzoquinone. Increased disulfide formation is considered to represent an index of oxidative stress produced by chemical. Increases in the level of protein and nonprotein disulfides in bladder suggest as observed in this study that administration of Na-o-phenylphenol to mice produced oxidative stress in bladder. Products of redox cycling of xenobiotics are known to cause cellular toxicity via altering the homeostasis of thiol status. Therefore, it is concluded that decreases in protein thiol contents either via alkylation and/or oxidation of sulfhydryl groups of proteins and increases in disulfide contents presumably by products of redox cycling of Na-o-phenylphenol may play a role in Na-o phenylphenol-induced cellular toxicity. PMID- 1616495 TI - Effect of pH and inorganic phosphate on creatine kinase inactivation: an in vitro 31P NMR saturation-transfer study. AB - The pseudo-first-order rate constant of rabbit muscle creatine kinase (CK), in the direction of ATP synthesis (kf), was determined by saturation-transfer 31P NMR. When pH was varied between 6.0 and 7.4, kf increased linearly at both 20 degrees C and 37 degrees c. The corresponding flux is very small between pH 6.0 and 6.5, in contrast to previous studies. Up to 50 h exposure of the CK enzyme to high concentrations of inorganic phosphate (Pi), a known inhibitor in certain situations, had negligible effect on enzymatic flux in the physiological pH range. Thus under in vivo conditions, such as in stroke, where pH falls as low as 6.2 and Pi rises to high levels, the rate of the CK reaction may be severely reduced due to pH but not due to high Pi concentrations. PMID- 1616496 TI - Chemiluminescence response of phagocytes in E. coli induced experimental ascending pyelonephritis. AB - The mechanism of tissue injury at the cellular level by following the chemiluminescence response of various phagocytes in E. coli induced experimental pyelonephritis in mice was investigated. There was a marked increase in the capacity of various phagocytic cells viz; renal neutrophils and macrophages peritoneal macrophages, blood monocytes and neutrophils to produce reactive oxygens species through the respiratory burst activity as monitored by the chemiluminescence response. The chemiluminescence response was observed to be increased significantly (p less than 0.001) with increasing days post infection in all phagocytic cells. However, the quantity of total reactive oxygen species produced per million cells was much more in the renal and peritoneal macrophages as compared to blood monocytes and neutrophils. The peak chemiluminescence response time was observed to be decreased from 4 to 2 minutes with the progression of the diseases. The implications of these findings have been discussed. PMID- 1616497 TI - Lack of association of Ca(2+)-calmodulin with the beta gamma-subunits of the photo-receptor G protein (transducin). AB - We previously reported that the beta gamma-subunit of transducin (T beta gamma) is composed of two components, T beta gamma-1 and T beta gamma-2 with distinctive gamma-subunits, T gamma-1 and T gamma-2, respectively. T beta gamma-2 enhances GTP binding to the alpha-subunit of transducin (T alpha) in the presence of a photobleaching intermediate of rhodopsin, while T beta gamma-1 is an inactive component with little enhancement ability (Fukada, Y., Ohguro, H., Saito, T., Yoshizawa, T., and Akino, T. (1989) J. Biol. Chem. 264: 5937-5943). To further elucidate the functional differences between T beta gamma-1 and T beta gamma-2, we examined the association of T beta gamma s with Ca(2+)-calmodulin, and the effect of Ca2+ on binding of GTP to T alpha in the presence of either T beta gamma-1 or T beta gamma-2. Ca2+ had no effect on the GTP binding activity of transducin and T beta gamma s could not associate with Ca(2+)-calmodulin, indicating that the relationship of T beta gamma with Ca(2+)-calmodulin of is different from that of the brain G protein. PMID- 1616498 TI - Effect of vanadate administration on polyol pathway in diabetic rat kidney. AB - Effect of oral administration of sodium orthovanadate for three weeks on polyol pathway in renal cortex and medulla was studied in control and alloxan diabetic rats. An enhancement in aldose reductase in cortex and medulla and sorbitol dehydrogenase in cortex was observed in alloxan diabetic rats. Despite depressed insulin secretion, vanadate treatment to diabetic rats counteracted hyperglycemia, normalized elevated enzyme activities and glucose level, prevented medullary sorbitol accumulation and markedly checked increase in kidney weight. These results show that vanadate causes marked improvement in renal hypertrophy and has an antidiabetogenic effect on polyol pathway in diabetic kidney. PMID- 1616499 TI - Regulation of poly(ADP-ribose) polymerase gene expression in mitogen-stimulated human peripheral blood mononuclear cells. AB - The level of mRNA for poly(ADP-ribose) polymerase in human PBMC increased 8 h after addition of PHA, reaching its maximum (9-fold over the basal level) 3-4 days after the stimulation and decreasing thereafter. mRNA maximum slightly preceded in time the maximal value of DNA synthesis. The half-life of poly(ADP ribose) polymerase mRNA, which is 1.2 h in quiescent PBMC, increased up to 3.4 h in stimulated PBMC. This PHA-induced stabilization of the mRNA for poly(ADP ribose) polymerase could account for the accumulation of the transcript in mitogen-treated PBMC. PMID- 1616500 TI - Effect of N-alkyl-N,N,N-trimethylamonium bromides on the auto-peroxidation of egg yolk phosphatidylcholine in liposomes. AB - N-alkyl-N,N,N-trimethylamonium bromides (cnTMA, n = number of carbons in alkyl) stimulate and inhibit the autoperoxidation of egg yolk phosphatidylcholine (EYPC) in liposomes at n less than 12 and n greater than 12, respectively, with maximum stimulation for n = 8. CnTMA intercalate between EYPC molecules (decreasing the yield of ROO. + RH----ROOH+R. reaction, where RH is an unsaturated EYPC acyl chain, R. - EYPC acyl radical, and ROO. - peroxy radical of the EYPC acyl chain) and disorder the hydrophobic region of the bilayer (increasing the oxygen solubility there and thus yield of R. + O2----ROO. reaction). The final level of oxidation is affected by a summation of the EYPC lateral separation and disordering effects. PMID- 1616502 TI - Transactions of the Topeka Psychoanalytic Society. PMID- 1616501 TI - Determination of the dissociation constants of pea diamine oxidase. AB - The activity of diamine oxidase [EC 1.4.3.6] (DAO) isolated from pea cotyledons was measured in Britton-Robinson buffers at pH range 5.0-9.6 by spectrophotometric method with E-1,4-diamino-2-butene as substrate. The enzyme has the highest activity at pH = 7.7 and in pH greater than 8.0 it is irreversible denaturated with time. The dissociation constants of the enzyme and enzyme-substrate complex were calculated by Dixon's method from plots of log Vmax, log KM and log Vmax/KM against pH. The pKEA = 6.5 suggests that histidine is in active site of DAO. PMID- 1616503 TI - [Critical comment on Helmut Thoma's essay on "Idea and reality in teaching analysis]. AB - H. Thoma's reformist ideas about training analysis are controversial. Beland reproaches Thoma for his insinuation that national as well as international training institutions for psychoanalysis supposedly have quantitative rather than qualitative motivations for increasing the length of training analyses--after the motto "the longer, the better". Against that the author claims that a future analyst, in order to qualify, has to become aware of the defenses against his fears of annihilation and loss. This goal cannot be reached in 300-400 sessions. He argues that the training institutions' artificial restriction on the length of analysis would influence the training analyst's analytical attitude negatively and would expose the candidate to institutional violence. PMID- 1616504 TI - Total quality management/continuous quality improvement in business and health care. PMID- 1616505 TI - Total quality management in American industry. AB - The definition of total quality management is conformance to customer requirements and specifications, fitness for use, buyer satisfaction, and value at an affordable price. The three individuals who have developed the total quality management concepts in the United States are W.E. Deming, J.M. Juran, and Philip Crosby. The universal principles of total quality management are (a) a customer focus, (b) management commitment, (c) training, (d) process capability and control, and (e) measurement through quality improvement tools. Results from the National Demonstration Project on Quality Improvement in Health Care showed the principles of total quality management could be applied to healthcare. PMID- 1616506 TI - TQM/CQI in business and health care. An overview. AB - TQM/CQI is increasingly being used by U.S. companies and the health care industry to improve their operations and profitability. TQM/CQI can be used by occupational health nurses to help focus efforts to improve their health services and demonstrate their value. TQM/CQI also is used by businesses to improve the quality and cost of external health services. Occupational health nurses who are knowledgeable in TQM/CQI can help assure the quality of external health services as businesses strive to reduce rising health care costs. PMID- 1616507 TI - Quality and quality improvement in occupational health nursing. AB - Donabedian first defined quality as the result of assessing the structures, processes, and outcomes of health care. The emphasis on quality assurance is changing to quality improvement. The definition of quality in health care has expanded to include the expectations and opinion of patients, their representative, and society. As the cost of health care continues to rise at twice the rate of inflation, business wants to know how health care dollars are spent. Occupational health nurses, to add value to the businesses in which they work, must be a part of the trend in measuring the quality of the products and services of their health services. PMID- 1616508 TI - Measuring satisfaction with medical case management. A quality improvement tool. AB - Medical case management's purpose is to improve the quality of health care and decrease medical expenses associated with high cost medical cases. Patient satisfaction can be used as a measure of the quality of medical case management. This investigation resulted in a reliable and valid questionnaire for assessing patient satisfaction and demonstrated mild satisfaction with the medical case management services of a vendor for a large manufacturer. Occupational health nurses can use this questionnaire to document the quality of medical case management that employees or their dependents are receiving and to assess the value received in conjunction with the costs incurred. PMID- 1616509 TI - Business coalitions on health care. An evolution from cost containment to quality improvement. AB - Business coalitions on health were unable to achieve community wide savings in health care costs in the 1980s. Some coalitions are using TQM/CQI to achieve high quality health care at a reduced cost. Although too recent to determine its success, the use of TQM/CQI in employer-provider partnerships built on trust and good data systems may be the best hope for private sector health care system reform. Health professionals knowledgeable about TQM/CQI can play an important role in helping their employers make new relationships with health care providers work. PMID- 1616510 TI - Software documentation: variations and uses. PMID- 1616511 TI - Prospective analysis of mental status progression in ethanol-intoxicated patients. AB - Distinguishing patients with uncomplicated ethanol intoxication from intoxicated patients with other causes of mental status depression is a common clinical dilemma. The authors serially tested mental status in a group of ethanol intoxicated patients to determine the interval over which mental status changes could be attributed to uncomplicated intoxication. Study patients were identified by (1) admission breath ethanol greater than or equal to 100 mg/dL; (2) ethanol related impairment necessitating further observation or treatment; and (3) not critically ill or exhibiting focal neurologic signs. Mental status scores (sums of specific indices of alertness, orientation, and agitation) were determined initially, 1 hour after arrival, then every 2 hours. Causes of mental status depression other than acute intoxication were diagnosed in 16 patients, while another 18 failed to completely normalize mental status by the time of emergency department discharge or hospital admission. The remaining 71 with uncomplicated ethanol intoxication required (mean +/- SD) 3.2 +/- 3.6 hours to normalize mental status scores. A large proportion, however, took considerably longer to normalize mental status: 15 (21%) took 7 or more hours, and three (4%) took as long as 11 hours. Although patients with ethanol-associated depression of mental status lasting 3 hours after emergency department admission should be carefully evaluated for other causes of mental status abnormalities, the authors' observations indicate considerable individual variation in the duration of mental status depression caused by uncomplicated ethanol intoxication. PMID- 1616512 TI - Oxygen saturation changes during the pediatric emergency department treatment of wheezing. AB - This study examined the oxygen saturation (OSAT) changes measured by pulse oximetry during emergency department (ED) bronchodilator treatment of wheezing patients. Data were collected prospectively on two cohorts (November 1987 to November 1988, 2,468 patients; and December 1988 to October 1990, 4,913 patients) presenting to a pediatric ED with wheezing-associated respiratory illnesses. Initial, posttreatment, and discharge OSAT was recorded in many of these patients. Improvement in OSAT following ED bronchodilator administration was noted in most patient groups. Initial OSAT was indicative of severity as measured by the need for hospitalization and the number of bronchodilator treatments administered in the ED. Subcutaneous epinephrine and aerosolized albuterol were compared in OSAT improvement and side effects. Aerosolized albuterol was not shown to be superior to epinephrine. Improvements in OSAT following bronchodilator administration documents the presence of relative preexisting hypoxemia which is reversed to some degree with bronchodilators. Pulse oximetry is an objective means of assessing asthma severity. PMID- 1616513 TI - The effect of ambient temperature extremes on tympanic and oral temperatures. AB - Exposure to ambient temperature extremes immediately preceding emergency department triage may affect tympanic membrane temperatures taken with infrared emission detection thermometers. In a prospective, unblinded study, 20 healthy subjects, on 2 separate days, underwent 15-minute exposures to hot (43.5 degrees C) and cold (-5 degrees C) temperature extremes in an environmental control room (ECR). Tympanic and oral temperatures were taken at baseline and at 2-minute intervals for 20 minutes after exiting the ECR. Rectal temperatures remained stable during the exposures. Oral temperatures rose significantly after hot exposure (P less than .05; max 0.4 degrees C) and briefly decreased after cold exposure (max 0.5 degrees C). Tympanic temperatures were elevated for 20 minutes after hot exposure (max 0.8 degrees C) and decreased briefly only in male subjects after cold exposure (max 0.7 degrees C). Individuals demonstrated wide variability in their temperature responses. Tympanic and oral temperatures taken within the first 20 minutes after exposure to outdoor temperature extremes may fail to accurately reflect the patient's true temperature. PMID- 1616514 TI - Cancer presentation in the emergency department: a failure of primary care. AB - Emergency departments are intended to be the location of entry into the health care system for patients with acute problems, such as injuries and myocardial infarctions. In contrast, cancer should optimally be detected during periodic health examinations, either through screening procedures or by early detection from signs and symptoms which prompt a routine visit to a primary care physician. This study was undertaken to describe patients who present to an emergency department with urgent symptoms and signs, are hospitalized, and subsequently diagnosed with cancer (ED group). One hundred twenty-nine patients were retrospectively studied. When compared with patients diagnosed in a primary care setting (tumor registry patients), the ED group was significantly older, more often male, had a significantly lower survival rate, and more frequent metastatic disease at diagnosis (P less than .001). The ED group accounted for 5.3% of the new tumor registry patients for the study years. Only 3.1% of the ED group had no insurance, and 21% reported no personal physician. Strategies are needed for patients and physicians to reduce the number of late-diagnosed cancer cases presenting in emergency departments. PMID- 1616515 TI - Comparative performance of the Baxt Trauma Triage Rule. AB - New methods of deciding which patients require trauma center transport continue to be devised. Baxt recently published a Trauma Triage Rule (TTR) using anatomic injury, blood pressure, and elements of the Glascow Coma scale which can be used to identify adult major trauma patients. The purpose of this study was to compare the TTR against three previously published trauma triage instruments; the Triage Revised Trauma Score, the Prehospital Index, and the CRAMS scale. We applied these rules to a data base of trauma patients transported by the Cleveland, Ohio Emergency Medical Services System. All four instruments identified adult trauma patients who either died or required emergent operations with sensitivities of at least .85. The specificity of the TTR exceeded that of the CRAMS. We conclude that the TTR is an effective means of identifying patients who either die or require emergent operation. PMID- 1616516 TI - The comparative efficacy of various multiple-dose activated charcoal regimens. AB - Multiple-dose activated charcoal therapy is used in the management of poisoning emergencies to enhance the elimination of enterohepatically and enteroenterically secreted toxins. This study was conducted to determine if increasing the frequency of activated charcoal administration would enhance the elimination of a toxin. In this crossover study, five healthy adult volunteers were randomly assigned to either a control phase or one of three study phases. Subjects in the control phase and each of the study phases received an intravenous infusion of aminophylline (8 mg/kg). During the study phases each subject additionally received activated charcoal 50 gm and activated charcoal 12.5 gm every hour, 25 gm every 2 hours, or 50 gm every 4 hours over a 8-hour period for a cumulative activated charcoal dose of 150 gm. Ten blood samples were obtained over 12 hours and analyzed for theophylline concentrations. Using area under the curve and half life calculations it was determined that each of the dosage regimens significantly reduced the reabsorption of theophylline and the plasma half-life when compared with control. There were no significant differences between any of the treatment groups. Decreasing the dose but increasing the frequency of activated charcoal administration is as effective as the traditional every 4 hour therapy regimen. PMID- 1616517 TI - Bretylium tosylate and electrically induced cardiac arrhythmias during hypothermia in dogs. AB - The effect of bretylium tosylate on plasma catecholamines and on electrically induced arrhythmias was evaluated in anesthetized hypothermic dogs. Bretylium at a dose of 7.5 mg/kg was administered prior to cooling from 37 degrees C to 27 degrees C. During cooling, the ventricular arrhythmia threshold (VAT) in control animals decreased from 10.1 +/- 1.9 to 4.4 +/- 1.3 impulses, while the VAT in bretylium-treated animals increased from 9.8 +/- 2.9 to 23.2 +/- 2.7 impulses. Catecholamine levels increased during cooling in all animals. In control animals, the epinephrine/norepinephrine ratio was unchanged, but in animals treated with bretylium tosylate, the ratio increased more than 10-fold (from 0.48 +/- 0.1 to 5.49 +/- 0.32 at 29.9 degrees C). The demonstrated increase in catecholamine levels during hypothermia suggests that the protection offered by bretylium tosylate against cardiac arrhythmias is not explained by modification of catecholamine levels, and is more likely due to an alteration of the electrophysiologic properties of cardiac tissues. PMID- 1616518 TI - An evaluation of the esophageal detector device using a cadaver model. AB - The study was conducted to evaluate the usefulness of an esophageal detector device (EDD) to correctly differentiate between esophageal and tracheal intubation. The study was conducted in the emergency department using 10 recently decreased cadavers (nine males, one female, age range 50-72 years). An 8-mm internal diameter endotracheal tube was placed orally into the trachea, and a second 8-mm ID tube was placed orally into the esophagus. Both tubes extended the same distance from the mouth, and the cuffs were not inflated. After placement of the tubes, the EDD was used by advanced life support providers (physicians, nurses, paramedics, and respiratory therapists) to determine if each tube was in the trachea or the esophagus. The persons who assessed the tube placement were not present when the tubes were placed into the cadavers. Multiple evaluators were allowed for each cadaver, but each evaluator only participated one time for each cadaver. The bulb of the EDD was squeezed by the evaluator, who then attached it to the endotracheal tube and rated the bulb inflation as immediate inflation, delayed inflation, or no inflation. Prior to participation in the study, evaluators were instructed in the use of the EDD. There were a total of 45 trials performed on the cadavers (median, four evaluations/cadaver, range, one eight). For the tracheal tube, the EDD inflated immediately in all cases; it was thus 100% correct in identification of tracheal intubation. For the esophageal tube, the EDD did not inflate in 44 cases, and in one case it filled with vomitus; it thus correctly identified esophageal intubation in all cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616519 TI - Improved compliance with quality assurance markers during trauma room resuscitation using trauma nurse specialists. AB - Trauma nurse specialists (TNS) have been shown to reduce the burden on house staff and to facilitate patient care on trauma wards. In the authors' facility, this expertise has been extended to the emergency department where TNS contribute to an improved standard of care by (1) nursing assessment and injury recognition and (2) continuity of care. As specially trained individuals, TNS expand upon the role of the emergency department staff nurse. The TNS could be shown to improve compliance with trauma resuscitation room protocol and quality assurance markers of direct patient management at a statistically significant level. PMID- 1616520 TI - Intravenous adenosine therapy accelerating rate of paroxysmal supraventricular tachycardia. AB - Two cases of paroxysmal supraventricular tachycardia are reported in which the administration of adenosine produced sustained elevation of the rate of paroxysmal supraventricular tachycardia. In each case, sinus rhythm was restored readily through the use of intravenous verapamil. This adverse reaction to adenosine has not been previously described. PMID- 1616521 TI - Severe hyperphosphatemia associated with hemorrhagic shock. AB - Hyperphosphatemia is an electrolyte abnormality that most frequently results from renal insufficiency and the attendant inability to excrete phosphorus (PO4) efficiently. A case is presented in which a young man with hemorrhagic shock developed severe hyperphosphatemia in the absence of renal failure. This is the first such case documented to the authors' knowledge. The prompt correction of the primary cause (ie, hypoperfusion and acidosis) resulted in a rapid return of PO4 levels to normal. This was probably related to the intracellular shift of PO4. Physicians should be aware of this electrolyte disturbance because it is not a well-recognized complication and because, in most cases, proper treatment of shock will also correct the elevated PO4. PMID- 1616522 TI - The incidence of pacemaker dysfunction during helicopter air medical transport. AB - A number of recent publications have raised concern regarding in-flight pacemaker dysfunction during air medical transport. Unfortunately the clinical importance of this problem is unknown. The authors' purpose was to examine the incidence of pacemaker use and malfunction during helicopter air medical transport, using an incidence (cohort) study of an air medical service of a tertiary-care teaching hospital. During the study period, April 1, 1987 through December 31, 1991 2,388 patients were air-transported. Cardiac patients constituted 72% of the total population. Pacemakers were used in 44 patients, temporary transvenous pacemakers in 35, permanent transvenous in five, and transcutaneous pacers in four patients. No rate-responsive pacemakers were transported. No episodes of pacemaker malfunction were observed (95% confidence interval 0 to .002 for the population as a whole). The authors conclude that pacemaker dysfunction during air medical transport is a very rare occurrence, in part due to the infrequent transport of patients requiring these devices. PMID- 1616523 TI - Unrecognized incomplete cervical spinal cord injury: review of nine new and 28 previously reported cases. AB - Nine patients with unrecognized incomplete cervical spinal cord injury are discussed. Four were sent home as normal, three were called hysterical, and two went undiagnosed during stupor or coma. A literature search revealed 28 additional cases. Eighty percent of these were males, two thirds were over 50 years old, and most had central or posterior cord syndromes. Falls with hyperextension, spondylosis, or disc disease, and motor vehicle accidents were the most common causes. Only one of the 37 had a cervical fracture. In some the neurologic problem was missed altogether; in others it was attributed to hysteria, intoxication, or to other neurologic or systemic diseases. Minor injuries without cervical fracture or dislocation, advanced age, unusual or changeable neurologic deficits, intoxication, and psychiatric problems all contributed to the confusion. PMID- 1616524 TI - Occult traumatic avulsion of an ovarian dermoid cyst. AB - This case report describes a unique presentation involving avulsion of an ovarian dermoid tumor which occurred as the result of blunt trauma secondary to a motor vehicle collision. Despite an unimpressive initial presentation and normal physical examination, the patient subsequently developed symptoms of severe hemorrhage requiring aggressive intravascular volume resuscitation. A ruptured ovarian dermoid tumor was eventually diagnosed by computerized axial tomography. A review of the literature by the authors did not reveal any similar cases of previous reports of this phenomenon. PMID- 1616525 TI - Review of all studies of cardiopulmonary resuscitation in animal models reported in the emergency medicine literature for the past 10 years. PMID- 1616526 TI - The current role of culdocentesis. PMID- 1616527 TI - Understanding the incomplete text: interpreting the emergency department patient. PMID- 1616528 TI - Activities of the Manpower Task Force of the American College of Emergency Physicians. PMID- 1616529 TI - Analysis of patient revisits to the emergency department. PMID- 1616530 TI - Critical care medicine: an annotated bibliography of the recent literature. PMID- 1616531 TI - Pediatric emergency care: an annotated bibliography of the recent literature. PMID- 1616533 TI - Untoward reaction to adenosine therapy for supraventricular tachycardia. PMID- 1616532 TI - Alternative training in emergency medicine. PMID- 1616534 TI - Metamucil bezoar: an unusual cause of small bowel obstruction. PMID- 1616535 TI - Glycopyrrolate for asthma. PMID- 1616536 TI - Digital endotracheal intubation. PMID- 1616537 TI - Traumatic carotideal dissection after blunt cervical injury: an elusive clinical entity. PMID- 1616538 TI - Ultrasound as a diagnostic tool. PMID- 1616539 TI - Twitching as a manifestation of occult uremia. PMID- 1616540 TI - Dystrophic calcification of a traumatic neuroma as an incidental finding. PMID- 1616541 TI - [Indisposition and acute dysphonia in the professional singer]. AB - In the event of vocal failure in professional singers, functional causes are at least as important as inflammatory mucosal lesions. Treatment should take both possibilities into account, together with the personality of the singer. PMID- 1616542 TI - [Assessing the quality of the speaking voice after therapy of T1 and T2 vocal cord cancers]. AB - All studies which analysed voice quality after T1 and T2 glottic cancer employed sustained vowels for evaluation. Sustained vowels can often be produced more clearly than expected in a severe degree of hoarseness in running speech. In this investigation voice quality was analysed by measuring the signal-to-noise-ratio (SNRc) in running speech. For evaluation these data were correlated to the scores from an auditive evaluation and from a clinical examination of the larynx considering functional parameters. 39 patients were examined after different therapies (primary radiation, chordectomy, frontolateral partial resection). The grading of the three different methods for characterisation of the voice quality correlated well. Therefore the SNRc is presumed to be a valuable additional method to the psychoacoustic voice evaluation. Comparison of voice quality after different therapies provided no significant difference between radiotherapy and chordectomy. The functional results after frontolateral partial resection were significantly less satisfying as expected. PMID- 1616543 TI - [Hereditary unilateral deaf-mutism as a variable manifestation of bilateral deaf mutism or hearing loss]. AB - A total of 2,519 patients with bilateral severe congenital deafness (deaf-mutism) from Central Switzerland were recorded during the period between 1834 to 1979. More recently, 31 persons with unilateral severe deafness were examined. By constructing genealogical charts going back to the 17th century, at least ten of these unilaterally deaf persons were shown to be related to patients with bilateral deafness (pedigrees I-IV). Some of them exhibited a more or less marked Klein- Waardenburg syndrome. The unilateral deafness of those patients was inherited and not acquired. Congenital unilateral deafness may be understood to be the result of the broad variability of the expressivity of acoustic defects. PMID- 1616544 TI - [Therapy of functional disorders of the craniovertebral joints in vestibular diseases]. AB - Cervicogenic vertigo is caused by functional disorders of the craniovertebral joints. Improvement of vertigonous symptoms by chiropractic treatment was often described. The therapeutic effect of chiropractic treatment in 28 patients with vertigo and purely functional disorders of the upper cervical spine or with a combination of functional disorders of the upper cervical spine and the labyrinth was evaluated. Improvement of vertigonous symptoms on patients with purely functional disorders of the craniovertebral joints as well as on patients with combined functional disorders of the craniovertebral joints and labyrinth could be seen. Two of the 28 patients showed persistent relief of symptoms and normalisation of cervical motility whereas the vestibular deficit persisted. One patient with persistent vestibular dysfunction showed recurrent malfunction of the upper cervical spine and vertigo. In our opinion chiropractic treatment is mandatory for the therapy of patients with vestibular affections and functional disorders of the craniovertebral joints. PMID- 1616545 TI - [Time course of nystagmus reactions after rotational stimulation (modified Veits long rotation method). I. Comparison of the nystagmus reactions of probands with normal equilibrium with those of patients with vestibular disorders]. AB - In the present study, all the nystagmus reactions following the rotatory test are represented graphically after being split up into successive time intervals of 5 seconds each. The range of reactions is illustrated by comparing healthy subjects with patients with acute lesions of the vestibular system. It has been shown that during the rotatory test no signs of habituation were to be seen. The use of the parameter "fast phase velocity" (FPV) of the nystagmus to analyze the nystagmus reactions did not prove meaningful. In particular the findings in patients with acute vestibular lesions show that the nystagmus reactions following rotatory stimuli of appropriate intensity increase only to a limited extent. When interpreting the results, the influence of spontaneous nystagmus which usually underlies acute vestibular disease, is discussed in detail. PMID- 1616546 TI - [Does the use of free transplanted jejunum segments in advanced laryngeal and hypopharyngeal cancer prolong survival? A matched-pair analysis]. AB - The effect of free transplanted jejunum autografts, inserted after resection of extensive squamous cell carcinoma of the larynx and hypopharynx is evaluated in terms of survival and the development of local and regional recurrences. In a matched-pair analysis, 22 patients with jejunum transplants were compared with 44 patients with the same performance status, in whom after laryngopharyngectomy, the pharynx had been closed with local mucosa. The cumulative survival rate was calculated using the Kaplan-Meier method; the statistical comparison of the survival curves of the two groups was made with the Mantel-Haezel test. Patients of the study group had a statistically significant (p less than = 0.01) better survival rate than those of the control group, the 50% survival rate being 36 and 11 months, respectively. Local recurrences occurred in 9.1% of the patients in both the study group and in controls, and regional recurrences in 40.8 and 43.2%, respectively. This militates against the possibility that the surgery in patients in whom reconstruction with jejunum was possible might have been more radical. Further, it may be speculated that the statistically significant better survival rate is due to the jejunum itself, presumably to a tumourprotective effect of the lymphatic tissue of the transplant. PMID- 1616547 TI - [Antineoplastic effectiveness and unwanted side effects of polychemotherapy of extensive oro- and hypopharyngeal cancers--results of a prospective therapy study with 5-FU/cisplatin versus 5-FU/carboplatin]. AB - 60 patients with advanced carcinomas of the oropharynx and hypopharynx underwent chemotherapy, either with 5-FU/Cisplatin (n = 30) or with 5-FU/Carboplatin (n = 30). The remission-rates (complete and partial remissions) were comparable in both groups. The rate of complete remissions, however, was statistically significant higher in the cisplatinum group (6 patients) than in the carboplatinum group (1 patient). 2 patients of the 5-FU/Cis-group and 4 patients of the 5-FU/Carbo-group developed a progressive disease during chemotherapy. Statistically significant differences were found in the nephrotoxic and myelotoxic side effects between both therapy groups: nephrotoxic side effects were more frequent in the 5-FU/Cis-group, whereas myelotoxic side effects occurred mainly in the 5-FU/Carbo-group. The chemotherapy with 5-FU/Carboplatin was better tolerated by the patients than in the 5-FU/Cisplatinum-group. In the 5 FU/Carbo-group especially a lower rate and severity of loss in weight, nausea, vomiting, alopecia and mucositis/stomatitis was observed. No statistically significant differences were found in ototoxic side effects between both groups. PMID- 1616548 TI - [Experimental studies of ischemia of the cochlea. Part 3: Pathophysiology]. AB - Selective interruption of cochlear blood flow is possible without operative manipulations in the middle or inner ear. By fitting a magnet into the external auditory canal and injecting iron filings into the cephalic vein is it possible to obtain an impaired inner ear in otherwise healthy experimental animals that can be kept alive for any length of time. The hearing loss induced by the ischemia normally remains unchanged over a period of weeks. The highly vascularised areas of the cochlea, namely the spiral ligament, the vascular stria, the spiral prominence and the root cells in the external spiral sulcus, as well as the spiral limbus were all clearly degenerated, but to different degrees. Pronounced vacuolisation of cells, degeneration of tissue, reduction of cellular elements, stasis in large and small blood vessels and morphological disorganisation were observed. The organ of Corti showed no changes worthy of note. On revascularisation of the spiral ligament and the spiral limbus with resumption of function, the organ of Corti can return to normal activity again. Repeat blood flow disturbances can also lead to recurrent sudden hearing loss and intermittent loss of hearing. PMID- 1616549 TI - [Interleukin-1-containing cells in cholesteatoma of the middle ear]. AB - Cholesteatoma of the middle ear and the adjacent temporal bone consists of hyperproliferative keratinizing squamous epithelium in the middle ear cavity, and is capable of destroying the bone. Interleukin-1 (IL-1), an autocrine growth factor for epithelial keratinocytes, is characterized by its capacity to initiate bone absorption. Using immunohistochemical methods, the distribution of two different species of interleukin, IL-1 alpha and IL-1 beta, in cholesteatoma tissue (Fig. 2), the skin of the external ear canal, and the retroauricular region was investigated (Fig. 1). Comparable amounts of both IL-1-species were found in all squamous epithelia examined, but interleukin in cholesteatoma epithelium was increased in comparison with normal epidermis. All cellular layers stained uniformly and equally strongly for IL-1 alpha and IL-1 beta, whereas the dead cells of the keratin layer were negative for both. Some intensely stained cells were found scattered in the connective tissue underlying the basal layer of the cholesteatoma (Fig 4). Using double staining techniques these cells were shown to be mainly macrophages (Fig 6). Our results suggest that IL-1 could be liberated from disintegrating keratinocytes and cells of the monocyte-/macrophage lineage, and stimulate the proliferation of the cholesteatoma epithelium in an autocrine manner, thus contributing to the increased bone destruction seen in cholesteatoma. PMID- 1616550 TI - [Synovial chondromatosis of the temporomandibular joint]. AB - Synovial chondromatosis of the temporomandibular joint is a relatively rare disorder. The diagnosis is often difficult because of the untypical clinical symptoms and an absence of radiological abnormalities. On the basis of a case report, the clinico-pathological, roentgenological and surgical features are discussed. After adequate surgical exploration with synovectomy the patient became symptom-free. PMID- 1616551 TI - [Liability for faulty surgical method in tympanoplasty with retro-auricular approach]. PMID- 1616552 TI - Global considerations affecting the health agenda of the 1990s. AB - The author explains why global problems, both known and unknown and unpredictable, are going to affect the health sector in the next few decades even more than they do today. Five examples are given of global health-related dilemmas that must be faced: (1) the worldwide aging of the population and the changing morbidity trends and physician supply needs this creates; (2) rising worldwide poverty, which has a direct relation to health status and has some new causes in this century; (3) ethical dilemmas, such as those resulting from new reproductive and life-prolonging technologies; (4) the need for adequate and affordable health care systems (the Canadian system is described and several misconceptions about it are clarified); and (5) the need to allocate scarce resources to meet practically infinite health care demands. The author concludes by listing some of the important actions that must be taken if we are to deal effectively with the dilemmas fostered by global problems: (1) people must be taught that their health status is the result of many factors in addition to their health care (e.g., socioeconomic status, lifestyle, the environment); (2) medical education must be refocused to prepare physicians to deal with global challenges; (3) there must be greater international cooperation (e.g., working together to share research and implement strategies to control AIDS); (4) countries must invest in worldwide efforts, such as family planning and primary education; and (5) international partnerships must be created to develop worldwide strategies, such as a global drug strategy. PMID- 1616553 TI - Technology assessment in medicine. AB - The author defines the concepts medical technology and technology assessment and presents a paradigm for the evaluation of medical technologies. He proposes a hierarchical assessment scheme in which level I, biologic plausibility, compares the technology's proposed mode of action with current biologic information and theory. Level II, technical feasibility, determines whether the technology can be delivered to the target population. Level III, intermediate outcomes, assesses whether the technology has a short-term impact on the biologic or physiologic process that is diseased. Level IV, patient outcomes, investigates the overall medical, psychologic, and financial impacts of the technology upon the patient, including unintended side effects and long-term morbidity and mortality. Level V, societal outcomes, measures the cost of the technology to society in terms of resource use, ethical issues, and social and political hazards. As an example, the author employs this scheme to analyze the use of screening tests for hypercholesterolemia. PMID- 1616555 TI - A program to foster residents' appreciation of the nurse's role. PMID- 1616554 TI - The potential for using non-physicians to compensate for the reduced availability of residents. AB - Both the number of residents and the amount of time existing residents have in which to carry out their activities may soon be decreasing. To consider the potential for alternative ways of staffing teaching hospitals, it is necessary to know how residents spend their time. The authors sought to learn this by conducting a time-motion study of eight internal medicine residents at two urban hospitals in New York City in 1988. The residents' activities were observed and coded by premedical students, and the authors independently classified the possible activities into (1) those that had to be done by a physician, (2) those that were educational only, and (3) those that could be done by a non-physician. A total of 1,726 activities of 67 kinds were coded, averaging 7.75 minutes each. The authors analyze and project their data using two models--the traditional model of care in which the physician is the primary medical manager of the patient, and an alternative model in which a midlevel practitioner, such as a nurse practitioner, would perform the day-to-day monitoring of patients. For example, the data indicate that in the traditional model, almost half of a resident's time is spent in activities that must be done by a physician, meaning that another kind of physician would be needed to do those activities if the resident were unavailable; but in the midlevel practitioner model, only around 20% of the activities would require a physician. The authors give detailed breakdowns of their data, estimate the kinds and numbers of non-physician health care professionals necessary to substitute for residents in appropriate activities, and review possible difficulties in implementing such substitutions. PMID- 1616556 TI - The health of the computer-based patient record. PMID- 1616557 TI - Strategic thinking about health care reform. PMID- 1616558 TI - Should faculty tutors for PBL groups be content experts? PMID- 1616559 TI - A program of integrative humanistic study for medical students. PMID- 1616561 TI - Sending medical students into the community as health instructors. PMID- 1616560 TI - A promising approach to teaching primary care in the ambulatory care setting. PMID- 1616562 TI - Recommendations for changing the residency selection process based on a survey of program directors. AB - The authors conducted a nationwide survey of program directors participating in the 1990-91 National Resident Matching Program (NRMP) in order to solicit the directors' responses to elements of the current residency selection process and to suggested revisions. Of 680 randomly selected directors, 469 (69%) responded to the survey questionnaire, using a five-point scale, from 1, indicating strong agreement, to 5, indicating strong disagreement. The directors agreed that the senior year was distorted by the selection process, that students were pressured into making early career decisions, and that there needed to be more structure to the senior year. The directors were also in agreement that interviews, the NRMP, and the uniform notification date were working well. But deans' letters, other letters of recommendation, the Universal Application, and appointment of unmatched students were considered to be in need of improvement. The development of a centralized residency application service with the electronic transmission of data received the directors' support. The authors recommend that a task force be convened to consider changes that would improve the selection process and would reduce disruption of the students' senior year of medical education. PMID- 1616563 TI - Effects of tutors with case expertise on problem-based learning issues. AB - At the University of Calgary Faculty of Medicine in 1991, the authors sought to determine the effects of tutors' levels of content expertise on learning issues generated within problem-based learning (PBL) tutorials. For an integrative course taken prior to clinical clerkships, the 70 students in the class of 1992 divided into ten small groups, which were facilitated alternately by content experts and non-experts. The authors found that--across 35 simulated-patient case encounters (24 with non-experts and 11 with experts)--when the groups had tutors with expertise in the clinical cases studied, the groups generated approximately twice as many learning issues per case, and these issues were approximately three times more congruent with the case objectives. In addition, when the groups had expert tutors they spent approximately twice as much time per case in overcoming identified learning deficiencies. The authors conclude that it is important for tutors (1) to be well informed about cases and case objectives and (2) to be well versed in the PBL tutoring process. PMID- 1616564 TI - Effects of expert and non-expert facilitators on the small-group process and on student performance. AB - At the University of Michigan Medical School in 1990, the authors investigated the effects of faculty facilitators' levels of content expertise on the educational process and learning outcomes of small-group teaching sessions. The study was conducted in a microbiology course for second-year students in which four small-group sessions were used to replace 38 hours of lecture and laboratory time. The interactions between 11 expert and ten non-expert faculty facilitators and 156 students were observed and coded. The students' levels of knowledge and satisfaction were measured. The results indicate that, although significant differences in faculty-student interactions were not observed, the students in the 11 groups led by the content experts had higher levels of satisfaction and higher examination scores. PMID- 1616565 TI - Association between clinical experiences in family practice or in primary care and the percentage of graduates entering family practice residencies. AB - In 1990 the authors surveyed all U.S. medical schools in order to solicit information about students' clinical experiences in family practice and in primary care. Of 126 schools, 104 (82.5%) responded. Survey data were correlated with each school's quartile ranking based on the average percentage of graduates who entered family practice residencies. A significant association (p = .0013) was found between required family practice clerkships or preceptorships and institutions ranked in the highest quartile (i.e., having more than 17% of their graduates enter family practice). A similarly significant association (p = .0056) was found for those 12 institutions that had more than 30% of their students select family practice options in required primary care clerkships or preceptorships. The authors suggest that active recruiting of students to take such options may increase the number of graduates who enter family practice. PMID- 1616566 TI - Developing and implementing a "basic science clerkship" for first-year students. AB - For over 15 years, human genetics at the University of Illinois College of Medicine at Chicago (UICMC) was taught exclusively through lectures. In 1989-90 the authors revised this course for the graduating class of 1993 in order to incorporate many features found in a clerkship experience, such as oral presentations and the exploration of differential diagnoses through patient cases. In addition to lectures, the revised course consisted of small-group work in concentrated blocks of time, involving both a library research project and problem-based learning, each of which contributed to (1) significant gains in student achievement compared with data from the class of 1992 and (2) extremely favorable assessments from the students and faculty. The format of a basic science clerkship is being adopted by other departments at UICMC. The authors suggest that this format could be used by other medical schools to integrate the basic and clinical sciences. PMID- 1616567 TI - Evaluations by three graduating classes of a required community health project. AB - The authors analyzed seniors' evaluations of the first three years of an intensive community health project at the Bowman Gray School of Medicine of Wake Forest University in 1988-89, 1989-90, and 1990-91. The project was designed to provide a public health perspective by having the students select, study, and propose solutions to a community health problem. Of 285 seniors, 240 (84%) completed evaluation questionnaires, using a five-point scale. The students' perceptions of the value of the project became steadily more favorable with each subsequent class; the classes of 1990 and 1991 rated the value of the project as being greater than that of most other experiences in their medical education. The project was more positively evaluated by the 106 responding students (44%) who planned to enter primary care specialties. The students who invested more time in the project also perceived its value to be greater. PMID- 1616568 TI - An instrument to evaluate alcohol-abuse interviewing and intervention skills. AB - At the University of Texas Health Science Center at San Antonio from 1988 through 1990, the authors developed the Alcoholism Intervention Performance Evaluation (AIPE), a rating instrument for the evaluation of alcohol-abuse interviewing and intervention skills. Factor analysis of 51 rating items identified seven factors that accounted for most of the variability among the items; 35 were retained and assigned to the factor with which they correlated most highly, thus resulting in a seven-factor instrument with 35 items. The AIPE overall score had an interrater reliability of .73 (for four raters each rating approximately 30 videotaped simulated-patient interviews) and a test-retest reliability of .89 (for one rater rescoring 20 interviews after one month). The authors suggest that the individual scores for the seven factors can be used to provide instructional feedback to trainees and that the overall score can be used to certify interviewer proficiency. PMID- 1616569 TI - MEDLINE training for medical students in the clinical curriculum. PMID- 1616570 TI - Scripted oral examinations of internal medicine students' clinical skills with simulated patients. PMID- 1616571 TI - Effect of context on the rating of students by faculty and housestaff in a clinical clerkship. PMID- 1616572 TI - Synthesis and pharmacological evaluation of some pyrazolo [3,4-e][1,4] diazepin 4,7-diones. PMID- 1616573 TI - Antiinflammatory pyrazolones and pyrazolidones: a study of their inhibition of 5 beta-dihydrocortisone reduction in rat liver cytosol. AB - Seven pyrazolone and pyrazolidone derivates, some of them widely used as analgesic and anti-inflammatory drugs, were tested for the inhibitory property of the 3 alpha-hydroxysteroid dehydrogenase of rat liver cytosol. The data obtained clearly show that, among pyrazolone and pyrazolidone derivates, the correlation between IC50 and therapeutic potency is not always verified. PMID- 1616574 TI - Synthesis and choleretic activity of 3-[2-(3-R', 4-R'', 5-R'''-benzyl)-5-R benzimidazol-1-yl]-butanoic acids. AB - On the ground of the evidentiated choleretic activity of 3-[2-benzylbenzimidazol 1-yl]butanoic acid, 28 new acids were prepared in order to evaluate the influence of suitable substitutions in either C5 of heteroring or C3', C4', C5' of benzyl group in position 2 on the choleretic activity. Pharmacological results after i.v. administration of 0.5 mmol/Kg in rats confirmed a general high choleretic activity that in eleven cases showed during the first 4 hours an increase of bile volume higher than 80%, that is superior to that produced by dehydrocholic acid. Only in a few cases the bile volume increase was less than 37% of basal value. PMID- 1616575 TI - A novel class of cholinergic agents structurally related to 2-morpholinol. AB - A series of esters and ethers of N-alkylmorpholin-2-ols, and their methiodides, which can be considered cyclic analogues of acetylcholine, were synthesized. The amines were obtained by acylation or etherification of morpholinols with the appropriate acyl chlorides and alcohols. All compounds were tested for their ability to interact with the muscarinic receptor M2 (guinea-pig atria) or M3 (rat ileum and urinary bladder) subtype. Some compounds, although endowed with relatively low potency, proved interesting for their organ selectivity. Some considerations on the structure-activity relationship are made and the results obtained with reference agonists and antagonists are also shown. PMID- 1616576 TI - Synthesis and aldose reductase inhibitory activity of pyridazine derivatives possessing acetic acid group. AB - N-acetic acid and S-acetic acid derivatives of 5-arylidene pyridazines were synthesized for evaluation as new aldose reductase inhibitors. Intrinsic activity for each compound was assessed by measuring inhibition of enzymatic activity in an isolated pig lens enzyme preparation. All prepared compounds exhibited a significant in vitro aldose reductase inhibitory effect (10(-5) M less than or equal IC50 less than or equal to 10(-4) M). It was found that lipophilicity was important in increasing activity. Furthermore, this activity (log 1/IC50) could be correlated directly to a lipophilic parameter (log kw) for the whole data set. PMID- 1616577 TI - Comparative sensitivity study of Clostridium perfringens towards 16 antibiotics from different classes. AB - A series of 16 antibiotics from different classes (5-nitro imidazoles, beta lactams, cyclins, macrolids, chloramphenicol) was examined for their bacteriostatic and bactericidal activities on 45 strains of Clostridium perfringens, with determination of MIC and MBC values. Several techniques of multivariate analysis were used in order to visualize differentiations in sensitivity profiles: Principal component analysis (PCA) and preferentially Correspondence factorial analysis (CFA). This approach revealed the efficacy of antibiotics from both general and family classifications. PMID- 1616578 TI - Synthesis and anthelmintic activity of carbamates derived from imidazo[2,1 b][1,3,4]thiadiazole and imidazo[2,1-b]thiazole. AB - The anthelmintic activity of 25 compounds, most of them carbamates, was determined. The in vitro results are interesting and show that an aromatic azapentalene can replace the benzimidazole ring without loss of its biological properties. The in vivo results, however, show that the compounds are devoid of practical interest. PMID- 1616579 TI - 1,5-Benzodiazepines. X. Dialkylamino substituted 1,5-benzodiazepine and [1,2,4]triazolo [4,3-a][1,5] benzodiazepine derivatives with inhibitory activity on PAF-induced platelet aggregation. AB - Novel 4-(dialkylamino) substituted (4, 5 c, 8) and 2,4-bis(dialkylamino) substituted (6) 1,5-benzodiazepine derivatives were synthesized. Both these new compounds and the substituted 4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepine-5 amines 2 a-h, recently described by us, were tested in vitro for their inhibitory activity on the PAF-induced aggregation of human platelets. Actually, bicyclic compounds 4 d, 5 c and tricyclic compounds 2 g, h showed a significant activity: in all them the dialkylamino substituent was the 4-(ethoxycarbonyl)-1-piperazinyl group. On the contrary, compounds 4 d, 5 c, 2 g,h showed practically no inhibitory activity when platelet aggregation was induced by ADP, A23187, or collagen. PMID- 1616580 TI - An 1,2,3-triazole derivative bioisoster of a potent in vitro prostaglandin synthesis inhibitor: preparation and biological activity. AB - This paper reports the preparation of the triazole ester 10, a methylenic bioisoster of an oxygenated compound A, effective inhibitor of the prostaglandin synthesis in vitro. Biological evaluation of 10 and of the corresponding acid 9 shows that the compounds maintain a good enzymatic inhibitory activity compared with indomethacin and aspirin. PMID- 1616581 TI - Macrocyclic polyesters. I. A novel class of 1,3-butandiol derivatives as potential antimicrobial agents. AB - This paper reports the synthesis of a novel class of macrocyclic tetraesters containing 1,3-butandiol sub-units by reacting the stannolan derivative of the diol with diacyl chloride. The structure of the possible isomers was assigned by spectroscopic data and comparison with samples otherwise prepared. Preliminary screening revealed that these compounds have low antimicrobial activity, although it is higher than that of the starting diol. PMID- 1616583 TI - p24 antibody production in p24 antibody-negative HIV-infected subjects. AB - To determine if HIV-infected patients with no detectable serum antibodies to p24 are producing antibodies to p24 (anti-p24), blood was obtained from 49 HIV infected patients at various stages of infection. Serum p24 antigen levels were measured and peripheral blood mononuclear cells were cultured for 1 week without mitogenic stimulation. The presence of anti-p24 in culture supernatants and sera was determined by radioimmunoprecipitation assays. Cells from 89% of the patients who had anti-p24 in their sera spontaneously synthesized anti-p24 in vitro. Similarly, cells from 83% of the HIV-infected patients who had no detectable anti p24 in their sera spontaneously produced anti-p24 in vitro. Thus the absence of anti-p24 in serum did not reflect suppression in the ability of patients' cells to synthesize and secrete antibodies to p24. However, cells from patients whose sera contained anti-p24 spontaneously synthesized more anti-p24 than did cells from patients whose sera lacked anti-p24, suggesting that these two groups of patients may represent individuals with inherently high or low responses to p24 epitopes, respectively. PMID- 1616582 TI - Human T-cell leukemia virus type-I/II (HTLV-I/II) serologic testing: the importance of assaying for the full complement of viral antigens. AB - Seventy-one Japanese adult T-cell leukemia (ATL) patients and 411 Japanese asymptomatic patients from HTLV-I endemic regions of southern Japan were found to be seropositive by radioimmunoprecipitation assay (RIPA). Of these 482 positive controls, 62% of ATL patients and 67% of the asymptomatic seropositive patients were found to harbor antibodies to p40x. Additionally, 333 preselected Japanese blood donors who were identified as seropositive by particle agglutination (PA) assay were further tested for antibodies to HTLV-I/II gene encoded envelope (env) or group specific antigens (gag) by means of enzyme-linked immunosorbent assay (ELISA) and RIPA. Concordance between ELISA and RIPA was noted in 318 samples (92.5%). Discordance between ELISA and RIPA was observed in 15 sera (7.5%)--2 were seropositive by ELISA and seronegative by RIPA and 13 were seronegative by ELISA and seropositive by RIPA. Seven of these 13 samples (53.8%) contained antibodies to p40x by RIPA and may represent ELISA false negatives on the basis of both clinical and laboratory data. Current HTLV-I/II ELISA kits may yield false negative results. Additional research into the development of rapid detection cost-efficient assays that test for the full compliment of viral antigens is needed. PMID- 1616584 TI - Regulation of maternal-fetal virus transmission in immunologically reconstituted SCID mice infected with lactate dehydrogenase-elevating virus. AB - Immunodeficient SCID (C.B-17 scid/scid) mice with persistent lactate dehydrogenase-elevating virus (LDV) infection failed to produce IgG anti-LDV antibodies, and during chronic infection transmitted virus infection to 95% of their offspring. In contrast, normal mice infected 15 or more days prior to giving birth produced IgG anti-LDV antibodies and transmitted LDV infection to only 0-46% of their fetuses. Transplacental transmission of LDV infection was dependent on the timing of maternal infection. Adoptive transfer of immune competence to LDV-infected SCID mice resulted in fetal protection from maternally transmitted virus infection. Fetal protection correlated with the presence of maternal IgG anti-LDV but not with fetal levels of IgG anti-LDV, and the levels of viremia in nonimmune SCID mice did not affect transplacental virus transmission. These results demonstrate the importance of maternal immunity in protecting the fetus from infection, and validate the use of this mouse model for investigation of immune mechanisms of transplacental virus transmission. PMID- 1616586 TI - Acute effects on health of smog episodes. Report on a WHO meeting. PMID- 1616585 TI - Adjuvanticity of stearyl tyrosine on the antibody response to peptide 503-535 from HIV gp160. AB - In this present report we compare the humoral immune response induced by immunization with an HIV-1 gp160 peptide corresponding to amino acid sequence 503 535 complexed with different adjuvants. Specifically, the antipeptide, anti-HIV-1 gp160 and neutralizing antibody responses were measured in groups of mice and baboons that received peptide 503-535 conjugated to a carrier protein in either saline, alum, or stearyl tyrosine. The highest antibody responses were induced when mice and baboons were immunized with peptide adsorbed on stearyl tyrosine. These data indicate that stearyl tyrosine represents a potent candidate as a nontoxic adjuvant not only for subunit viral vaccines, but also for HIV peptides. PMID- 1616587 TI - Linear quadratic model and biologically equivalent dose for single fraction treatments. AB - The linear quadratic model has been used to calculate the biologically equivalent dose for single fraction treatments. Our calculations suggest that for late reacting tissue, such as the brain, a single fraction of 1440 cGy is equivalent to a conventional treatment of 5000 cGy in 25 fractions. PMID- 1616589 TI - Dosimetry of small field electron beams. AB - Measurements of the central axis depth dose curves, isodose profiles and field size dependence of the output factors for small field electron beams from a Varian Clinac 18 linear accelerator have been performed. Energies of electron beams studied were 6, 9, 12, 15, and 18 MeV. Circular fields of 1, 2, 3, 5, and 8 cm diameter were obtained from cerrobend shields attached to the bottom face of a 15 x 15 cm2 electron cone applicator. Measurements were carried out in a water phantom with an ionization chamber and a silicon diode detector and in a polystyrene phantom with Kodak XV-2 film. For all energies studied, as the field size of the electron beam becomes smaller: (1) the depth of maximum dose shifts toward the surface, (2) the depth of 90% and 80% dose, which are common dose prescription depths, becomes smaller, (3) the surface dose increases, and (4) the dose fall-off region becomes more gradual. The output of the electron beam reduces significantly with reduction in electron beam field size as a consequence of lack of lateral equilibrium. Hence, for accurate treatment planning for small electron fields, it is essential that the beam characteristics be individually measured. PMID- 1616588 TI - Estimation of the mean effective organ doses for total body irradiation from Rando phantom measurements. AB - For the total body irradiation (TBI) procedure, it is necessary to compare the mean dose obtained from the tissue or organs and the estimated dose equivalent value from the computer program. Due to the easy-access of the Rando phantom and repeatability of TLDs and its output, the results from the experiment are quite encouraging for the verification of the dose distributions from total body irradiation at the given prescribed monitor units. The estimation of effective dose equivalent particularly across the lung sections was studied by combinations of using arms as the scatter volume to compensate for the inhomogeneity across the breast portion, as well as using the spoiler for skin-sparing purposes. The results were based upon various beam quality such as 4 MV, 6 MV, and 10 MV X rays. One series of experiments performed for this survey to ascertain the dose equivalent of the tissues was conducted. This paper describes the method and procedure for comparison between the measured data and computed data as a reference in the dosimetry of total body irradiation. Comparison of the measured and computed data for the largest collimated field shows that the calculated dose rates do not differ by more than 2% from the measured data. Because uncertainty is inherent in non-patient-like phantoms, the calculated data may be served as a reference for the dosimetry. For the total body irradiation setup, considering the radiation field size and treatment distances commonly employed, we conclude that the best combination of the patient setup will be (1) laying both arms down as compensation for lung inhomogeneity, and (2) the spoiler, which is made of acrylic about 8 mm thick and functions like a bolus, is needed to reduce the skin sparing effects and contribute the uniform dose distribution. The beam spoiler with the frame stands near the patient during the treatment. PMID- 1616590 TI - Couch rotation technique for treatment of head and neck cancer. AB - This paper reviews a technique for patients with head and neck cancer that achieves adequate inferior margins on the lateral ports by rotating the treatment couch. This technique has the advantage of avoiding multiple ports in an area of high risk or over a tumor mass. PMID- 1616591 TI - Junctioning adjacent fields using border films and table top measurements. AB - We present a technique for matching adjacent treatment fields over the spine. Our approach relies on identifying vertebral bodies and correlating their position to the table top markings present on the simulator table. The vertebral body levels are verified with films taken with the isocenter at the borders (nondivergent border films) so the "true" borders are identified. This is in contrast to using the usual divergent films, which may misrepresent the field borders with respect to the vertebral body level. An additional space between fields may be added as a precaution against overlap. PMID- 1616592 TI - A technique for postoperative irradiation of carcinomas of the larynx and hypopharynx. AB - Postoperative radiation is commonly employed for advanced lesions of the larynx and hypopharynx which have undergone a laryngectomy. It is technically difficult to achieve a homogeneous distribution of irradiation throughout the treatment volume because of the marked variation in contour across the treated area. We have described a technique which employs a 15 degrees lateral kick-out of the treatment table and a 15 degrees gantry angle above the horizontal for each of two lateral fields. This technique has certain advantages over other techniques previously described in the literature. By adding a gantry angle of 15 degrees above the horizontal to the kick-out lateral position of the table, we have found that we were able to decrease the amount of irradiation to the shoulder, to improve the dose to the posterior superior mediastinum, to lower the applied dose, and to avoid a hot spot overlying the spinal cord in the superior posterior portion of the field. This technique is particularly useful in patients who lack the flexibility to move their shoulders posteriorly and inferiorly. PMID- 1616593 TI - The surface doses from orthovoltage x-ray treatments. AB - Measurements have been made of the surface dose with treatment cones and lead shielding used with orthovoltage x-ray systems. Both devices significantly increase the surface dose, probably by the generation of photoelectrons. The surface dose depends upon the shape and material of the cone and the x-ray energy. The surface dose can be 500% higher than the dose measured with a Baldwin Farmer chamber. The significance of these doses is discussed in the light of recent information on the thickness of the epithelium. It is suggested that every effort be made to reduce the surface dose by using low atomic number material between the lead and the patient surface. PMID- 1616594 TI - A simple method for use in QC of CT for radiation therapy treatment planning. AB - A simple procedure for monitoring constancy of spatial measurement and CT number determination from CT images used in radiation therapy treatment planning is described. The procedure uses low-Z material rods glued to the underside of the CT table insert and does not require a special phantom. Measurements are made on the same patient images used for treatment planning. Deviations from predetermined baseline values outside quality control limits of +/- 2 mm in spatial resolution and +/- 20 CT numbers in density can be detected with a confidence level of 97% or better. PMID- 1616595 TI - Determination of ion recombination loss by two-voltage method for pulsed radiation beams. AB - The ion recombination loss is one of the most important correction factors for dosimetry using ionization chamber especially for the measurement of high intensity pulsed radiation beam. The two-voltage method has been used frequently for the correction of ion recombination loss. Several ways to approximate the method are presented. Comparisons were carried out to check the validity of the approximation. Using four ionization chambers of different types and shapes, measurements were made to obtain the optimal value of the ratio for the two voltages. PMID- 1616596 TI - Radiotherapy treatment planning for prostate cancer in patients with prosthetic hips. AB - Patients diagnosed with prostate cancer may also have a prosthetic hip. When planning radiotherapy for these patients, one must consider the attenuation of the dose when the beam passes through the prosthetic hip. It is best to avoid administration of radiation to the target through the prosthesis. Example treatment plans are evaluated. The potential advantages and disadvantages of each plan are reviewed. PMID- 1616597 TI - Quantification of doses to mediastinal lymph nodes in Hodgkin's disease. AB - Hodgkin's disease is highly curable today. Radiotherapy (RT) is the treatment of choice in the early stages. A mantle field is often used in the RT of Hodgkin's disease, and the technique and dosimetry are quite complex. We used computerized tomography (CT)-based dosimetry to determine doses delivered to different mediastinal nodes with the commonly used technique in Hodgkin's disease that was originally described by Kaplan. We used dose-volume histograms to determine doses to various groups of nodes in nine patients. Significant inhomogeneity (30%, 30%, 35%, 35%, 30%, 40%, 35%, 35%, and 30% in the nine patients) in dose distribution was found within the mediastinum. With the advent of 3-dimensional CT-based treatment planning, we are able to quantify such inhomogeneities. The question arises whether a homogeneous, lesser dose can achieve equal results. Average doses and "effective doses" were also calculated. The "effective doses" in eight patients (for a prescribed dose of 44 Gy) with a midline posterior spinal cord block added at 20 Gy were 37.3 Gy, 34.3 Gy, 36.0 Gy, 38.4 Gy, 35.8 Gy, 38.1 Gy, 36.7 Gy, and 36.7 Gy, respectively. A homogeneous dose equivalent to effective dose may achieve the same control as an inhomogeneous dose delivery. Prospective 3-D dosimetric studies are required to confirm this concept. PMID- 1616598 TI - Asymmetric field calculations. AB - A simple method for performing manual dose calculations in asymmetric fields is proposed. The method is based on a generalized central-axis dose calculation equation for which open- and wedged-field off-axis provisions have been made. A calculation form designed to document the calculation and simplify the calculation process is presented. Lastly, the required off-axis dosimetry data obtained from a dual-energy accelerator are shown. PMID- 1616599 TI - The human hepatic cytochromes P450 involved in drug metabolism. AB - The cytochromes P450 are a superfamily of hemoproteins that catalyze the metabolism of a large number of xenobiotics and endobiotics. The type and amount (i.e., the animal's phenotype) of the P450s expressed by the animal, primarily in the liver, thus determine the metabolic response of the animal to a chemical challenge. A majority of the characterized P450s involved in hepatic drug metabolism have been identified in experimental animals. However, recently at least 12 human drug-metabolizing P450s have been characterized at the molecular and/or enzyme level. The characterization of these P450s has made it possible to "phenotype" microsomal samples with respect to their relative levels of the various P450s and their metabolic capabilities. The purpose of this review is to compare and contrast the human P450s involved in drug metabolism with their related forms in the rat and other experimental species. PMID- 1616600 TI - Environmental concentrations and aquatic toxicity data on diflubenzuron (dimilin). AB - The insecticide diflubenzuron (DFB) is commonly used in various mid-Atlantic states for suppression of gypsy moths in hardwood forests. DFB is potentially toxic to nontarget biota because it can enter aquatic systems through aerial application or runoff after precipitation events. Based on this concern, the objectives of this study were to: (1) compile, review, and synthesize literature on the fate, persistence, and environmental concentrations of DFB in both freshwater and saltwater environments; (2) compile, review, and synthesize acute and chronic aquatic toxicity data on DFB effects on freshwater and saltwater organisms; (3) assess possible risk to aquatic biota associated with the use of this insecticide in one specific area (Maryland); and (4) recommend future research based on the data gaps identified from this study. DFB has low solubility in water and exists as a technical grade (TG) and wettable powder (WP) formulation. The toxicity of both formulations is similar at concentrations less than 10 micrograms/l. Organic matter is a major factor influencing the adsorption and degradation of DFB in freshwater, saltwater, and sediment. The half-life of this insecticide in freshwater is approximately 3 days at a pH of 10 and temperature of 36 degrees C. At lower pH conditions of 6 and at the same temperature, DFB is more persistent since half-life values of approximately 9 days have been reported. The half-life of DFB in soil is less than 14 days when the particle size was approximately 2 microns. The half-life is generally greater in cool, dry soil than in hot, wet soil. Aquatic vegetation acts as a sink for DFB by gradually adsorbing the chemical and releasing it over a period of time. Freshwater organisms demonstrated a wide range of sensitivity to DFB. Sensitivity was dependent on body composition (i.e., exo- vs. endoskeleton), trophic level, and life stage. During acute exposures, aquatic invertebrates were more than 25,000 times as sensitive to DFB than fishes. The most acutely sensitive species tested was the Amphipod, Hyallela azteca (96-h LC50 = 1.84 micrograms/l). A mature Plecopteran, Skwala sp., was the most resistant invertebrate species tested in acute tests (96-h LC50 greater than 100,000 micrograms/l). In chronic tests, DFB concentrations of 1 microgram/l or greater were reported to eliminate populations of various Plecopteran (stoneflies) and Ephemeropteran (mayflies) species after 1 month of exposure. A 30-day LC50 of 0.1 micrograms/l DFB was also reported for the Tricopteran, Clistorinia magnifica.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1616601 TI - Lesions of the fornix but not the amygdala impair the acquisition of concurrent discriminations by rats. AB - Rats with lesions in either the fornix, the amygdala, or both were compared with control animals on the acquisition of three different concurrent object discrimination tasks. In the first task the animals received one trial per day on each of six pairs of stimulus objects ('spaced' condition). In the second task the animals received four trials per day on each of six stimulus pairs ('standard' condition), and in the last task the animals received 36 trials on each of two stimulus pairs in just a single day ('massed' condition). Animals with fornical lesions were impaired on all three conditions. In contrast, the amygdala lesions only affected the 'massed' condition and then only when the animals had to select the 'non-preferred' stimulus. Although animals with combined amygdala and fornical lesions were impaired on all three conditions there was no evidence that their deficit was greater than that in the animals with lesions restricted to just the fornix. In view of the evidence that concurrent discrimination learning offers an appropriate test for anterograde amnesia these findings are seen as consistent with the notion that the hippocampus, but not the amygdala, is critically involved in the mnemonic processes disrupted by amnesia. PMID- 1616602 TI - Spontaneous forelimb grasping in free feeding by rats: motor cortex aids limb and digit positioning. AB - Forelimb use in grasping food during free feeding was studied in control and motor cortex damaged rats using videoanalysis and Eshkol-Wachmann Movement Notation (EWMN). Rats detected food using olfaction, grasped it by mouth, and then sat and reached for it with their paws. Once held in the paws, the food was eaten. A reach consists of: (1) lifting the forelimbs from the ground, (2) positioning them elbows-in, so that the paws were adjacent to the mouth, and (3) clasping the food in the digits. These movements were executed mainly with the upper arm. Limb movements were usually bilaterally symmetrical but when asymmetrical movements occurred, the forelimb least involved in weight support initiated the movement. As the limb was positioned for grasping, the aperture of the digits was adjusted to anticipate the size of the food and the food was grasped and manipulated with the tips of the digits. Following unilateral motor cortex lesions to the forelimb area: (1) the ipsilateral limb (good limb) initiated lifting, positioning, and grasping movements, (2) appropriate adjustment of the digits of the contralateral limb (bad limb) and grasping were impaired, and (3) when contact with food was lost, the bad limb adopted an extended, closed-fist spastic posture and could not be repositioned independently. The gross impairments cleared within 2 weeks, and after a few months impairments were infrequently observed. These findings show that: (1) spontaneous food grasping uses both proximal movements of the limb and distal movements of the digits, (2) digit aperture anticipates food size in reaching, and (3) motor cortex damage impairs both proximal and distal movements more profoundly when the limb is used independently than when it is used in conjunction with the good limb. The results are discussed in relation to kinematic studies on primates and humans. PMID- 1616603 TI - The role of histamine in the anterior hypothalamus and its functional interaction with the hippocampus on exploratory behavior in adult male rats. AB - The possible effects of histamine (HA) locally applied into the preoptic area (POA) on hippocampus-mediated behaviors were studied in adult male rats. Animals were double-implanted unilaterally with microinjection cannulae into POA and hippocampus (HPC). In experiment 1, HA was injected into POA and pyrilamine (H1 HA antagonist) or ranitidine (H2-HA antagonist) were microinjected into the ipsilateral HPC in two different doses. In Experiment 2, HA was injected into POA and the histamine antagonists were microinjected into the contralateral HPC. Ten min later the animals were tested in an automatic monitor activity. Horizontal, ambulatory and vertical movements were measured as general motor exploratory behaviors. Contact time (in seconds) to a circular metal rack positioned in the center of the animal activity monitor was also recorded as goal-directed exploratory activity. Results of Experiment 1 showed that HA in POA exerted an inhibitory influence on general motor behaviors and also on goal-directed activity. Ipsilateral administration of HA-antagonists into HPC blocked the HA effect on behavior. Results of Experiment 2 showed that the administration of the HA-antagonists in any of the two doses used were not able to block the depressive actions on behavior caused by HA into POA. In conclusion, data suggest that POA is linked to the ipsilateral HPC through histaminergic influence to control behavioral patterns induced by novelty. PMID- 1616604 TI - Vibrissal roughness discrimination is barrelcortex-dependent. AB - We have investigated the contribution of the neocortical vibrissal representation within the posterior medial barrel subfield (PMBSF) to the high performance levels obtained by rats in a complex roughness discrimination task mediated by vibrissal inputs. Nine binocularly occluded rats were trained in a two-choice roughness discrimination until they obtained the 85% correct response criteria. Subsequently, the PMBSF was localized by electrophysiological recordings and bilaterally ablated. The locus and extent of the cortical lesions were confirmed by histological analysis after additional training and testing. There was no evidence of task retention after the cortical lesion and barrelless rats were unable to obtain prelesion discriminative performance levels when stimulation was restricted solely to vibrissal cues. After extensive postlesion training, four of these rats were allowed to palpate the discriminanda with their forepaws. Under these conditions rats rapidly reached the 85% correct criterion once again. The present results indicate that the PMBSF is essential for complex tactile discrimination when sensory information is obtained through the vibrissae by active palpation. This deficit is specific for the vibrissal system, the PMBSF is not essential to solve the same tactile discrimination task when the source of the somatosensory information is provided by other non-vibrissal cutaneous sensory receptors. PMID- 1616605 TI - Non-cholinergic action of exogenous acetylcholinesterase in the rat substantia nigra. I. Differential effects on motor behaviour. AB - In the substantia nigra a non-cholinergic action of acetylcholinesterase has been demonstrated on motor behaviour. At the cellular level, electrophysiological studies have shown not only excitatory actions of AChE, but also inhibitory effects in response to larger amounts of the protein. In this study the possible dose-dependent effects of AChE were therefore explored in relation to circling behaviour. Both 'ipsiversive' turning (towards side of infusion and indicative of net decreased activity in the nigrostriatal pathway) and 'contraversive' turning (away from side of infusion and indicative of net increased activity) was observed for at least 2 weeks following a single unilateral AChE infusion. Ipsiversive turning occurred in 15-20% of animals in each group irrespective of dose. However, the actual number of animals exhibiting contraversive turning increased with increasing dose, whilst those not responding decreased. The most critical factor for direction of response appeared to be related not to dose, but cannula placement; infusion of AChE into more posterior regions of the substantia nigra evoked contraversive circling, whereas there appeared to be a discrete site in the anterior nigra in which AChE induced ipsiversive turning. This study thus suggests that subpopulations of nigrostriatal neurons show differential responsiveness to AChE. PMID- 1616607 TI - Analysis of the ongoing behavior of rats in non-matching-to-sample: improved acquisition and performance is related to facilitation of investigation. AB - In a non-matching-to-sample task, rats were trained according to the conventional procedure in which the displacement of the sample object resulted in food reinforcement and termination of the sample period. Compared to these animals, rats given a longer duration sample period, and rats not reinforced with food for displacing the object in the sample period, improved their rate of acquisition and their accuracy of performance. Detailed behavioral observations indicated that improved discrimination was related to increased investigation of the objects in the sample period, reduced side preferences, and an inclination to examine both objects in the test period. The results suggest that more accurate performance was related to the generalization of sampling habits from the sample period to the test period. PMID- 1616606 TI - Non-cholinergic action of exogenous acetylcholinesterase in the rat substantia nigra. II. Long-term interactions with dopamine metabolism. AB - Within the substantia nigra acetylcholinesterase (AChE) has a novel non cholinergic action that is functionally manifest as chronic circling behaviour in rats. The aim of this study was to explore the possible biochemical mechanisms that could underlie the long-term behavioural effects of this protein, infused unilaterally into one substantia nigra. A single treatment of acetylcholinesterase induced modest but consistent circling behaviour in the presence of a systemic amphetamine challenge for the maximum time tested, up to 50 days: comparable infusions of saline were without effect. When animals received a challenge of the direct dopamine agonist apomorphine, no AChE-induced circling was observed: this result suggested that the phenomenon did not entail a down-regulation of striatal dopamine receptors. On the other hand, a challenge of the dopamine uptake inhibitor nomifensine resulted in AChE-induced circling that was indistinguishable from that seen in the presence of amphetamine: hence the circling behaviour seen could be attributable to an AChE-induced increase in availability of extracellular dopamine. In animals where AChE caused contraversive rotation, indicative of an enhanced activity in the nigrostriatal pathway, there was a significant elevation in the dopamine content of the striatum on the treated side. It is concluded that AChE can chronically enhance the release of dopamine from the nigrostriatal pathway such that motor behaviour is correspondingly modified, but to an extent sufficiently modest to avoid compensatory synaptic reversal mechanisms. PMID- 1616608 TI - Diencephalic lesions, learning impairments, and intact retrograde memory following acute thiamine deficiency in the rat. AB - Previous studies have shown that following an acute bout of pyrithiamine-induced thiamine deficiency (PTD) rats are impaired in learning appetitively and aversively motivated T-maze tasks. The present study examined if PTD-treated rats exhibit both anterograde and retrograde memory loss of an aversively motivated spatial navigation task. Histological examination revealed two consistent lesions in the PTD treated rats: a bilateral, symmetrical destruction of medial thalamus centered on the internal medullary lamina (IML), and a lesion of the medial nucleus of the mammillary body. In Experiment 1, control and recovered PTD rats were trained to find a hidden platform in a Morris water maze. PTD rats with the IML lesion were impaired in learning the water maze task but were eventually able to perform as well as controls and PTD animals without the IML lesion. In Experiment 2, half of the pretrained CT animals underwent thiamine deficiency (PTD2), were recovered, and subsequently were tested for retention of the platform location. The remaining CT animals and the PTD1 group were also tested for retention. No significant group differences were observed on any of the four postretention trials. When compared to their performance on the last four preretention trials, the performance of PTD1 and PTD2 animals with IML lesions were similar to those of the controls. These results demonstrate that acute thiamine deficiency in rats produces damage of medial thalamic and mammillary body nuclei, a mild anterograde learning deficit, but no loss of retrograde memory of the Morris water maze task. PMID- 1616609 TI - Scopolamine deficits in negative patterning discrimination: evidence for a role of the central cholinergic system in retention but not acquisition of non-spatial configural association learning. AB - The effects of scopolamine (0.1 mg/kg s.c. and 0.6 mg/kg s.c.) were assessed on the acquisition and retention of a negative patterning discrimination task in rats. At 0.1 mg/kg scopolamine did not affect either acquisition or retention of the task. At 0.6 mg/kg scopolamine did not affect acquisition but did impair retention of the task. This impairment is likely to be centrally mediated as N methyl scopolamine (0.6 mg/kg s.c.) did not affect retention. Lack of effect of scopolamine on acquisition of the task indicates that the central cholinergic system is not a necessary substrate of the acquisition of non-spatial configural associations. The scopolamine-induced deficit in retention of the task, suggests that there may, however, be a central cholinergic involvement in the retention/retrieval of this type of learning. PMID- 1616610 TI - Double dissociation of fornix and caudate nucleus lesions on acquisition of two water maze tasks: further evidence for multiple memory systems. AB - The present study examined the effect of lesions of the caudate nucleus or fimbria-fornix on the acquisition of two water maze tasks. In both tasks, two rubber balls with different visual patterns were used as platforms (i.e., cues). The "correct" cue was attached to a submerged rectangular platform and could be mounted by an animal to escape the water. The "incorrect" cue was attached to a thin round pedestal and could not be mounted. In a spatial version of the task, the correct cue was located in the same quadrant of the maze on all trials, whereas the visual pattern on the cue was varied from trial to trial. Lesions of the fornix, but not the caudate nucleus, impaired acquisition of this spatial task in relation to control animals. In a simultaneous visual discrimination version of the task, the correct cue on all trials was one with a specific visual pattern, and the spatial location of the correct cue was varied from trial to trial. Lesions of the caudate nucleus, but not the fornix, impaired acquisition of this visual discrimination task in relation to control animals. The double dissociation observed supports the hypothesis that the hippocampus and caudate nucleus are parts of systems that differ in the type of memory they mediate. PMID- 1616611 TI - Object exploration and reactions to spatial and nonspatial changes in hooded rats following damage to parietal cortex or hippocampal formation. AB - Hooded rats with bilateral lesions of the anterior part of the hippocampal formation (HIP), anterior region of the posterior parietal cortex (APC), or posterior region of the posterior parietal cortex (PPC) were compared with controls for their exploration of 5 objects in an open field, habituation of locomotion and object investigation, and response to spatial and nonspatial change. First, all groups displayed habituation of both locomotor and exploratory activity. Second, controls selectively reexplored displaced objects, and APC lesioned rats reexplored all objects, whereas PPC- and HIP-lesioned rats failed to react to the spatial change. Third, a novel object induced reexploration in all groups. The results are consistent with the roles of the HIP and PPC in spatial information processing. Moreover, the APC and PPC are involved in attentional effortful processing and visuospatial information processing necessary for spatial representation, respectively. PMID- 1616613 TI - Memory in the chick: multiple cues, distinct brain locations. AB - Training chicks on a one-trial passive avoidance task results in memory-dependent synaptic remodeling in the intermediate medial hyperstriatum ventrale (IMHV) and lobus parolfactorius (LPO). Because pretraining IMHV lesions are amnestic and posttraining IMHV lesions are not, the functional significance of this remodeling requires explanation. Chicks use various cues to classify and remember objects. If the IMHV were concerned with memory for only one such cue, then posttraining IMHV lesions would not lead to "amnesia" because animals would still avoid the aversive bead using other contextual cues. This hypothesis was tested using a color discrimination task. IMHV lesions, but not LPO lesions, impair color discrimination, suggesting that the IMHV may be involved in classifying and remembering the bitter bead on the basis of color. Thus, even simple associations are stored in the brain in the form of multiple, dispersed representations. PMID- 1616612 TI - Loss of hippocampal CA1 pyramidal neurons correlates with memory impairment in rats with ischemic or neurotoxin lesions. AB - Rats were trained for 20 days in a modified T maze to perform an invariant, tactile discrimination and a variable, delayed spatial discrimination, and then were exposed either to 30 min of transient forebrain ischemia or to low- or high dose ibotenic acid to damage the dorsal hippocampus bilaterally. Only rats exposed to ischemia or high-dose ibotenic acid demonstrated impaired performance during 30 postoperative test days on both aspects of the task (p less than .05). Volume of hippocampal damage did not predict performance. However, the extent of CA1 pyramidal neuron loss correlated significantly with performance on the delayed spatial discrimination (p less than .01). Damage to the dentate gyrus and CA2-3 did not correlate with performance. These results support the view that the hippocampus, in particular the CA1 region, is crucial for certain types of memory performance. PMID- 1616614 TI - Stimulation at a site of auditory-somatosensory convergence in the medial geniculate nucleus is an effective unconditioned stimulus for fear conditioning. AB - The medial division of the medial geniculate nucleus (MGm) and the posterior intralaminar nucleus (PIN) are necessary for fear conditioning to an auditory conditioned stimulus (CS), receive both auditory and somatosensory input, and project to the amygdala, which is involved in production of fear conditioned responses. If CS-unconditioned stimulus (US) convergence in the MGm-PIN is critical for fear conditioning, then microstimulation of this area should serve as an effective US during classical conditioning, in place of standard footshock. Guinea pigs underwent conditioning (40-60 trials) using a tone as the CS and medial geniculate complex microstimulation as the US. Conditioned bradycardia developed when the US electrodes were in the PIN. However, microstimulation was not an effective US for conditioning in other parts of the medial geniculate or for sensitization training in the PIN or elsewhere. Learning curves were similar to those found previously for footshock US. Thus, the PIN can be a locus of functional CS-US convergence for previously for footshock US. Thus, the PIN can be a locus of functional CS-US convergence for fear conditioning to acoustic stimuli. PMID- 1616616 TI - Potentiation or diminution of discrete motor unconditioned responses (rabbit eyeblink) to an aversive pavlovian unconditioned stimulus by two associative processes: conditioned fear and a conditioned diminution of unconditioned stimulus processing. AB - In two experiments using the rabbit conditioned eyeblink preparation, the conditions under which a Pavlovian conditioned stimulus (CS) potentiates or diminishes the unconditioned response (UR) were examined. The results indicated that, after discrimination training (CS+ vs. CS-), the CS+ diminished UR amplitude at the training interstimulus interval (ISI). When CS+ trials were segregated into trials on which a conditioned response (CR) did or did not occur, the CS+ diminished the UR when it elicited a CR, but not when a CR failed to occur. When the CS-unconditioned stimulus (US) interval was lengthened to 10 s, the CS+ reliably potentiated the eyeblink UR on CR trials but did not potentiate responding on trials on which a CR was absent. The results are discussed in terms of the modulatory effects and temporal properties of conditioned fear and an associatively produced decrement in US processing. PMID- 1616615 TI - Frequency-specific receptive field plasticity in the medial geniculate body induced by pavlovian fear conditioning is expressed in the anesthetized brain. AB - Fear conditioning modifies the processing of frequency information; receptive fields (RF) in the auditory cortex and the medial geniculate body (MGB) are altered to favor processing the frequency of the conditioned stimulus (CS) over the pretraining best frequency (BF) and other frequencies. This experiment was designed to determine whether brief conditioning in the waking state produces RF plasticity that is expressed under general anesthesia. Guinea pigs bearing electrodes in the MGB received 20 trials of tone-shock pairing in a single training session. RFs were determined with animals under ketamine anesthesia before conditioning and 1-3 hr and 24 hr after conditioning. Frequency-specific RF plasticity was evident for both postconditioning periods: The BF shifted toward or to the CS frequency, responses to the BF decreased, and responses to the CS increased. Broadly tuned cells developed greater RF plasticity than narrowly tuned neurons. The results demonstrate that the specific neuronal results of brief learning experiences can be expressed in the anesthetized brain. PMID- 1616617 TI - Conditioning using a cerebral cortical conditioned stimulus is dependent on the cerebellum and brain stem circuitry. AB - Electrical stimulation of the auditory cortex (AC) was used as a conditioned stimulus (CS) in the rabbit conditioned eyeblink preparation to trace the functional anatomical connections between the AC and the circuitry underlying this conditioned response. Conditioning was shown to be dependent on the cerebellar interpositus nucleus and the pontine nuclei (PN), structures that are essential for conditioning using a peripheral CS. The results suggest that the cerebellum and associated brain stem circuitry are a necessary part of the memory trace circuit for the conditioned eyeblink response, even when the cerebral cortex is artifically engaged as a CS by electrical stimulation. The results also suggest that the PN are a site of convergence between the CS circuit subserving classical conditioning for peripheral stimuli and the AC, and may therefore be a site where the AC can modulate more elaborate forms of conditioning. PMID- 1616618 TI - Visually guided locomotion, distractibility, and the missing-stimulus effect in hooded rats with unilateral or bilateral lesions of parietal cortex. AB - When hooded rats with bilateral lesions of Krieg's area 7 (parietal cortex) were trained to locomote toward visual targets in a runway, they ran less accurately than did controls, although unilaterals ran accurately. When flashing lights were presented unexpectedly during their run, bilateral parietals were less disrupted than were controls, but they failed to show total neglect. Unilateral paritals turned toward distracters on either side but turned preferentially toward distracters contralateral to the intact hemisphere, particularly when distracters occurred bilaterally and simultaneously. Effects due to the omission of expected distracters were similar in parietals and controls. Rat parietal cortex is not essential for the redirection of attention to stimuli notable for their unexpected presence or absence, but parietal cortex may resolve interhemispheric competition. The results suggest a homology between parietal cortex in rat and primate. PMID- 1616619 TI - Ontogeny of feeding motor patterns in infant rats: an electromyographic analysis of suckling and chewing. AB - During mammalian ontogeny, there is a transition from suckling to the chewing of food. The question was asked: Is suckling a neuromuscular precursor to chewing, or are suckling and chewing independent systems? Electromyograms (EMGs) were recorded in rat pups of ages 6, 9, 12, 15, 18, and 21 days from the superficial masseter, anterior digastric, sternohyoideus, and genioglossus muscles during suckling and chewing. The EMG patterns of the 3 components of suckling behavior (nipple attachment, rhythmic sucking and the stretch response) are distinctive from one another and reflect the musculoskeletal biomechanics of suckling. Chewing EMGs are present by 12 days of age and attain the adult pattern by 18-21 days of age. During nipple attachment, pups exhibit a motor pattern that is similar to that of adult chewing, but other aspects of suckling differ from chewing in some EMG features. Comparison of EMGs between behaviors and between ages allowed interpretation of the degree of contunity of muscular activity across the suckling-to-chewing transition. PMID- 1616620 TI - Odors can induce feeding motor responses in the terrestrial mollusc Limax maximus. AB - Highly developed odor learning was shown in the terrestrial slug Limax maximus. In addition, several key cellular elements of the neural network that controls ingestive feeding have been identified. The results of 3 experiments demonstrate an interaction between odor input and ingestive feeding in that olfactory stimulation with behaviorally attractive odors summed with tactile stimulation from plain agar to produce ingestion of plain agar. Agar ingestion did not occur in the absence of attractive odor stimulation. The adequacy of odor stimulation to trigger agar ingestion was altered by associative learning. Innately attractive odors rendered repellent by associative learning no longer triggered agar ingestion, whereas innately repellent odors rendered attractive by conditioning triggered agar ingestion. The newly discovered feeding command cells in the Limax cerebral ganglion are a logical cellular locus for this interaction. PMID- 1616621 TI - Hemispheric priming by meaningful and nonmeaningful symbols in language-trained chimpanzees (Pan troglodytes): further evidence of a left hemisphere advantage. AB - Hemispheric priming was examined in 3 language-trained chimpanzees (Pan troglodytes) using a simple reaction time paradigm. Subjects were required to hold down a response button until the occurrence of a response cue. A warning stimulus was presented to either the left visual field (LVF) or the right visual field (RVF) before the response cue occurred. No warning stimulus was presented on control trials. The warning stimuli were geometric communicative symbols from two semantic categories: foods and tools. A third set of warning stimuli were familiar geometric symbols. Dependent measures included reaction time and the number of false-positive responses. Reaction-time data indicated an RVF advantage in priming when the warning stimuli were food or tool symbols. No significant visual half-field differences were found for familiar symbols, but a trend toward an RVF advantage was observed. These effects were enhanced when subjects responded with their left hand. False-positive data also indicated an RVF advantage for the food and tool warning stimuli. The data indicate that hemispheric asymmetries for processing communicative symbols are present in language-trained chimpanzees. PMID- 1616622 TI - Single crystals of long DNA molecules. AB - We have grown single crystals of long DNA molecules, 54 and 65 base pairs in length which encompass the binding site of the Xenopus protein transcription factor IIIA (TFIIIA). These molecules are considerably longer than those previously crystallised. X-ray diffraction shows that the crystals are ordered to a resolution of 9 A. The DNA molecules are arranged side to side in layers which are orientated at 120 degrees with respect to adjacent layers. The phosphate backbones of molecules in adjacent layers are interdigitated in both the major and minor grooves. The intensity distribution indicates that the average structure is B-like, although CD spectra in solution are more consistent with the structure, intermediate between A- and B-, found in crystals of a nonamer fragment of the binding site. The B-character in our crystals may therefore be impressed by the tight packing between layers. PMID- 1616623 TI - An eclectic DNA structure adopted by human telomeric sequence under superhelical stress and low pH. AB - We have found, with the aid of 2-D gel electrophoresis, that double-stranded human telomeric repeat, (T2AG3)12.(C3TA2)12, being cloned within a plasmid, forms a protonated superhelically-induced structure. Experiments on chemical and enzymatic probing also indicate that the human telomeric repeats adopt an unusual structure. We have proposed an eclectic model for this structure in which four different elements coexist: a non-orthodox intramolecular triplex stabilized by the canonical protonated C.G*C+ base-triads and highly enriched by noncanonical base-triads; the intramolecular quadruplex formed by a portion of the G-rich strand; the single-stranded region encompassing a portion of the G-rich strand and, probably, the (C,A)-hairpin formed by a portion of the C-rich strand. PMID- 1616624 TI - Electron microscopic observations of the effects of anthraquinone derivatives on plasmid DNA. AB - Electron microscopy was used to analyse the precipitation of DNA observed when mixed with two tripeptide derivatives of mitoxantrone, with or without a 5,8 dihydroxy group (DHQ-GHK and Q-GHK, respectively) on the anthraquinonic ring. This precipitation was compared to that obtained with the basic drugs, mitoxantrone (DHAQ) and ametantrone (AQ). The effects of these compounds on the supercoiling of form I and the lengthening of form II of pBR322 DNA molecules, respectively, were evaluated. A strong lengthening of the DNA molecules was observed for ametantrone (max: 57%), but only 32% for Q-GHK, both at r (drug/base pari) = 250. With the dihydroxy derivative DHQ-GHK, it was not possible to show more than a 10% increase in length because DNA molecules were not measurable at r greater than 100. Only Q-GHK relaxed supercoiled molecules at the low r values of 10. Complex phenomena of condensation-precipitation were observed with these two tripeptide derivatives. In addition to a strong lengthening of form II DNA molecules, AQ induced specifically the formation of toruses, and DHAQ that of large organized DNA condensation. The variety of the aggregations is described and discussed with regard to the antitumor properties of these derivatives, and the literature concerning the various descriptions of DNA aggregation. PMID- 1616625 TI - Ionic strength dependence of the binding of methylene blue to chromatin and calf thymus DNA. AB - The binding of the intercalating dye methylene blue (MB) to chromatin and to free DNA has been studied as a function of ionic strength at very low binding ratios (1 MB/400 DNA bases) using absorption spectroscopy. With increasing salt concentration MB is displaced from chromatin to a higher extent than from DNA. The free energy change for MB binding to chromatin is found to be approximately 5 kJ/mole lower than for binding to DNA. This difference can be explained by the reduced number of high affinity binding sites in chromatin due to the presence of histone proteins. The difference in binding energy is virtually independent of the degree of chromatin condensation and also of the valence of counter ions, suggesting that neither the affinity for, nor the number of intercalation sites in the linker DNA is markedly changed upon the salt-induced condensation. The unaffected thermodynamics of the linker binding suggests that factors such as DNA superhelicity and the electrostatic influence from the chromatosomes remain unchanged during chromatin condensation. PMID- 1616626 TI - Flexibility of DNA in 2:1 drug-DNA complexes--simultaneous binding of two DAPI molecules to DNA. AB - Simultaneous binding of two DAPI molecules in the minor groove of (dA)15.(dT)15 B DNA helix has been simulated by molecular mechanics calculations. The energy minimised structure shows some novel features in relation to binding of DAPI molecules as well as the flexibility of the grooves of DNA helices. The minor groove of the helix expands locally considerably (to 15 angstroms) to accommodate the two DAPI molecules and is achieved by positive propeller twisting of base pairs at the binding site concomitant with small variations in the local nucleotide stereochemistry. The expansion also brings forth simultaneously a contraction in the width of the major groove spread over to a few phosphates. These findings demonstrate another facet of the flexible stereochemistry of DNA helices in which the local features are significantly altered without being propagated beyond a few base pairs, and with the rest of the regions retaining the normal structure. Both the DAPI molecules are engaged in specific hydrogen bonds with the bases and non specific interactions with phosphates. Stacking interactions of DAPI molecules between themselves as well as with sugar-phosphate backbone contribute to the stability of the complex. The studies provide a stereochemical support to the experimental findings that under high drug-DNA ratio DAPI could bind in the 2:1 ratio. PMID- 1616627 TI - Conformations of Cyclobut-A and Cyclobut-G: structural resemblance to nucleosides and incorporation into double helical DNA. AB - Conformational energy calculations have been carried out on two modified nucleosides Cyclobut-A and Cyclobut-G using the methods of molecular mechanics (MM2) obtainable in the computational software MacroModel. Conformations were generated as a function of the torsion angles equivalent to the glycosidic and backbone torsions in deoxyribonucleotides. The structural resemblance of the energy minimized models of the modified nucleosides to their corresponding deoxyribonucleosides has been investigated. It is found that conformations which lie within 3 kcal/mole of the global minimum do resemble the overall shape and volume of the B-DNA nucleoside. Following this result, two deoxypentanucleotides d(GCGCG).d(CGCGC) and d(ATATA).d(TATAT) were model built incorporating cyclobut-G and cyclobut-A, respectively. These were then energy refined using the molecular mechanics package AMBER. The resultant structures demonstrate that cyclobut-A and cyclobut-G can be easily accommodated in double helical polynucleotides with minimal overall distortions. PMID- 1616628 TI - Monte Carlo simulation of hydration of the guanine-uracil pairs with guanine in two tautomeric forms: contribution of water bridging to relative stability of mispairs. AB - Results are presented from Monte Carlo simulation of hydration of guanine-uracil mispairs by 25 and 50 water molecules. The hydration shells of three mispairs formed between "normal" dioxo form of uracil (U) and three forms of guanine ("normal" amino-oxo tautomer G and two rotamers of the "rare" amino-hydroxy tautomer G*) depend on the tautomeric forms of the guanine molecule. The simulation shows the important role of hydration effects on the relative stability of the mispairs. PMID- 1616629 TI - Fuzzy molecular surfaces. AB - Surface area of a macromolecule, accessible to a solvent, is defined and calculated, taking into account the probabilistic character of atomic positions due to the high frequency atomic vibrations. For a given a space point, we consider a probability of the event, that this point is covered by a macromolecule. A volume is defined as a space integral of this probability field. The envelope, accessible to a solvent molecule center, becomes fuzzy, existing only in a probabilistic sense. The accessible area is defined as a derivative of the envelope volume with respect to the probe size. PMID- 1616630 TI - An efficient automated computer vision based technique for detection of three dimensional structural motifs in proteins. AB - As the number of available three dimensional coordinates of proteins increases, it is now recognized that proteins from different families and topologies are constructed from independent motifs. Detection of specific structural motifs within proteins aids in understanding their role and the mechanism of their operation. To aid in identification and use of these motifs it has become necessary to develop efficient methods for systematic scanning of structural databases. To date, methods of structural protein comparison suffer from at least one of the following limitations: (1) are not fully automated (require human intervention), (2) are limited to relatively similar structures, (3) are constrained to linear alignments of the structures, (4) are sensitive to insertions, deletions or gaps in the sequences or (5) are very time consuming. We present a method to overcome the above limitations. The method discovers and ranks every piece of structural similarity between the structures compared, thus allowing the simultaneous detection of real 3-D motifs in different domains, between domains, in active sites, surfaces etc. The method uses the Geometric Hashing Paradigm which is an efficient technique originally developed for Computer Vision. The algorithm exploits the geometrical constraints of rigid objects, it is especially geared towards recognition of partial structures in rigid objects belonging to large data bases and is straightforwardly parallelizable. Computer Vision techniques are for the first time applied to molecular structure comparison, resulting in an efficient, fully automated tool. The method has been tested in a number of cases, including comparisons of the haemoglobins, immunoglobulins, serine proteinases, calcium binding proteins, DNA binding proteins and others. In all examples our results were equivalent to the published results from previous methods and in some cases additional structural information was obtained by our method. PMID- 1616631 TI - The affinity of DNA-microtubule protein complexes and their disruption by tubulin binding drugs. AB - Using the gel shift assay system, we have measured the apparent affinity constant for the interaction of two different DNAs with MAP proteins found in both total calf brain microtubules and heat stable brain preparations. Both DNAs studied contained centromere/kinetochore sequences- one was enriched in the calf satellite DNA; the other was a large restriction fragment containing the yeast CEN11 DNA sequence. Complexes formed using both DNAs had similar Kapp values in the range of 2.1 x 10(7) M-1 to 2.0 x 10(8) M-1. CEN11 DNA-MTP complexes had by far the highest Kapp value of 2.0 x 10(8) M-1. The CEN11 DNA sequence is where the yeast kinetochore of chromosome 11 is formed and where the single yeast microtubule is bound in vivo. The CEN11 conserved region II known binding sites (dA/dT)n runs- for mammalian MAP2 protein, are in good agreement with this higher Kapp value. The effects of the classical tubulin binding drugs colchicine, podophyllotoxin and vinblastine on the DNA-MAP protein complex stability were investigated by determining the drug concentrations where the complexes were destabilized. Only the complexes formed from total microtubule protein (tubulin containing) were destabilized over a wide drug concentration range. Heat stable brain protein complexes (no tubulin) were largely unaffected. Furthermore, it took 10-100 fold higher drug concentrations to disrupt the CEN11 DNA complexes compared to the calf thymus satellite DNA enriched complexes. These data support our previous results suggesting that there is a DNA sequence dependent interaction with MAP proteins that appears to be conserved in evolution (Marx et. al., Biochim. Biophys. Acta. 783, 383-392, 1984; Marx and Denial, Molecular Basis of Cancer 172B, 65-75 1985). In addition, these results imply that the classical tubulin binding drugs may exert their biological effects in cells at least in part by disrupting DNA-Protein complexes of the type we have studied here. PMID- 1616632 TI - Dynamic light scattering studies on hydrodynamic properties of fibrinogen fibronectin complex. AB - A high molecular weight 'cryogel' was obtained as insoluble complexes by cold incubation at near-freezing temperatures from heparinized plasma of patients with rheumatoid arthritis. After the cryogel was solubilized at 37 degrees C, 1:1 complex of fibrinogen and fibronectin was purified at room temperature by affinity chromatography on a gelatin-Sepharose 4B. Hydrodynamic properties of the complex were investigated as a function of temperature and NaCl concentration using a dynamic light scattering. The diffusion coefficients of the complex at 20 degrees C decreased with increasing of NaCl concentration as free fibronectin. The complex appears to be a more compact form at low ionic concentration, which is associated with conformational changes of fibronectin. The diffusion coefficient of the complex at 20 degrees C in 0.05 M TrisHCl(pII7.4) containing 0.5 M NaCl was estimated as 8.5 x 10(-8) cm2s-1. The complex did not dissociate over the temperature range from 20 to 37 degrees C. The diffusion coefficients of the complex decreased significantly at 12 degrees C and 40 degrees C. The thermal denaturation of fibrinogen molecule in the complex was observed at 40 degrees C. The CONTIN analysis of the light scattering data showed that the complex associated to form higher aggregates at 15 degrees C, but not at near-freezing temperature. The equilibrium between the complex and higher aggregates appeared reversible. PMID- 1616633 TI - Cellular transcription factors involved in the regulation of HIV-1 gene expression. PMID- 1616634 TI - Patterns of immunoglobulin G subclass reactivity to HIV-1 envelope peptides in children born to HIV-1-infected mothers. AB - OBJECTIVE: To analyse the pattern of immunoglobulin (Ig) G subclasses specific for HIV-1 envelope peptides in sera from HIV-1-infected mothers and their newborns. We sought to determine whether there was a selective transfer of antibodies from mother to child, and to establish diagnostic or prognostic properties by analysing HIV-1 peptide-specific IgG isotypes. DESIGN AND METHODS: Parallel sera from 12 HIV-1-infected mothers and their newborn children were analysed for IgG subclass responses to six HIV-1 envelope peptides by enzyme linked immunosorbent assay. Levels of IgG were compared with levels of IgG1 and IgG3 to an immunodominant gp41 peptide in children's sera obtained during the first months of life. In a longitudinal study of 16 children born to HIV-1 seropositive mothers, of whom 11 were infected, the IgG1 and IgG3 responses to peptides representing an immunodominant epitope of gp41 and the principal neutralizing determinant of the gp120 V3 region were analysed. RESULTS: IgG1 and IgG3 were found to constitute the predominant peptide-specific antibody responses. A parallel distribution of IgG subclass reactivity was seen in maternal and paediatric sera. There was no evidence of selective antibody transfer. Comparable levels of IgG and IgG1 to the immunodominant peptide were seen in infected and uninfected children, while the IgG3 had disappeared in the majority of uninfected children. A decrease in peptide-specific IgG1 and IgG3 levels was observed in sequential sera from uninfected children, although the kinetic profile varied. Sera from infected children showed de novo synthesis of IgG1 and/or IgG3 binding to the selected HIV-1 peptides. Most children with rapid disease progression failed to produce IgG1 and/or IgG3 to the V3 peptide. CONCLUSION: Analysis of IgG subclass kinetics to selected HIV-1 peptides might be a useful additional diagnostic and prognostic tool in evaluating HIV-1 infection in children born to seropositive mothers. PMID- 1616635 TI - Evaluation of an enzyme immunoassay for the combined detection of antibodies to HIV-1, HIV-2, HTLV-I and HTLV-II. AB - OBJECTIVE: To assess the sensitivity and specificity of a newly-developed assay (Bioelisa HIV-1 + 2, HTLV-1 + 2) for the simultaneous detection of HIV-1, HIV-2, HTLV-I and HTLV-II antibodies in human serum or plasma specimens. METHODS: A panel of 775 well characterized serum or plasma samples was studied. This included samples confirmed to contain antibodies to HIV-1 (n = 46), HIV-2 (n = 19), HTLV-I (n = 49) and HTLV-II (n = 12), samples containing low titres of anti HIV antibody (n = 14) and samples collected during HIV seroconversion (n = 36). Eighty-three sera samples which were reactive in one or more HIV or HTLV screening assays, but which could not be confirmed to contain anti-HIV-1/2 or anti-HTLV-I/II antibodies, were also examined. RESULTS: Excluding the seroconversion samples and those selected on the basis of false reactivity in other screening assays, the Bioelisa kit had a sensitivity of 100% for antibody to all four viruses and a specificity of 98.8%. The ability of the kit to detect anti-HIV during seroconversion was similar to that of several other synthetic HIV antigen-based screening kits currently in use. CONCLUSIONS: Our findings indicate that the Bioelisa kit is sufficiently accurate to screen for both HIV and HTLV infections and that it warrants larger scale trials. Its use might allow blood donor screening for HTLV infection to be introduced more widely at modest extra cost [corrected]. PMID- 1616636 TI - Clinical correlation of the immunological markers of HIV infection in individuals from Thailand. AB - OBJECTIVE: To evaluate the usefulness of T-cell subsets, beta-microglobulin (B2M), p24 antigen and anti-p24 antibodies as differentiating and prognostic markers in HIV-infected Thai patients. DESIGN: Sixty-one HIV-infected patients in various stages of disease (six AIDS, three AIDS-related complex, 34 persistent generalized lymphadenopathy and 18 HIV-asymptomatic) were followed prospectively for 2 years. Patients were examined and immunological markers assessed every 6 months at least. Any HIV-related complications were treated symptomatically and clinical staging was re-evaluated at each visit. Due to financial constraints, none of the patients were given antiretroviral drugs. METHODS: T-cell subsets were enumerated by indirect immunofluorescence using OKT4 or OKT8 for T-helper and T-suppressor cells, respectively. beta 2M and p24 antigen were quantified by enzyme-linked immunosorbent assay and anti-p24 antibodies were by immunoblot assay. RESULTS: Our preliminary study revealed that the decrease in CD4+ T-cells or anti-p24 titre and the increase in p24 antigen or beta 2M correlated well with disease staging, as defined by the Centers for Disease Control. Absolute number and percentage of CD4+ T-cells, absolute number of CD8+ T-cells, beta 2M level and p24 antigen and anti-p24 antibody levels at entry could be used as reliable prognostic markers for HIV progression. The combination of p24 antigen with the number of CD4+ T-cells substantially increased the prognostic value, compared with either used alone. CONCLUSIONS: The annual rate of clinical progression from asymptomatic to symptomatic HIV infection in our study was 6.8%. The results we obtained in this preliminary study may be used as baseline data for planning future therapeutic interventions in Asian patients. PMID- 1616638 TI - Mother-to-infant transmission of HIV and hepatitis C infections in children born to HIV-seropositive mothers. PMID- 1616637 TI - Disease progression and early predictors of AIDS in HIV-seroconverted injecting drug users. The Italian Seroconversion Study. AB - OBJECTIVE: To evaluate the risk of developing AIDS and to identify early markers of disease progression in injecting drug users (IDU). DESIGN: Prospective study. SETTING: Sixteen centres throughout Italy. PATIENTS, PARTICIPANTS: Four hundred and sixty-eight IDU for whom it was possible to estimate the date of HIV seroconversion. MAIN OUTCOME MEASURES: Progression to AIDS. RESULTS: Twenty-six subjects developed AIDS during a median follow-up period of 42 months. The risk of developing AIDS was 21% within 7 years following seroconversion. Age greater than 25 years at seroconversion was associated with more rapid disease progression. Progression was similar for men and women. Continued drug injection did not accelerate progression to AIDS. Among the laboratory markers studied, CD4+ cell count at the first HIV-positive test was the best predictor of disease progression. Results were confirmed using multivariate analysis. CONCLUSIONS: Our findings indicate the importance of the role played by age in accelerated disease progression, which may be determined by a more rapid decline in CD4+ cell number in older HIV-infected IDU. PMID- 1616639 TI - Lack of correlation between acidified HIV p24 antigen and plasma viraemia. PMID- 1616640 TI - Incidence of hepatitis C, hepatitis B and HIV infections among drug users in a methadone-maintenance programme. PMID- 1616641 TI - Application of blood transfusion guidelines in a major hospital of Kinshasa, Zaire. PMID- 1616642 TI - Seroprevalence of HIV-1 in patients attending Modena Hospital, northern Italy. PMID- 1616643 TI - Monitoring the growing workload for the treatment of people with AIDS (PWA) in a university hospital, 1987-1990. PMID- 1616644 TI - Neuropsychological assessment of HIV-seropositive hemophiliacs. PMID- 1616645 TI - Differences in marital status among men reported with AIDS. PMID- 1616646 TI - Simple and efficient production of the core antigens of HIV-1, HIV-2 and simian immunodeficiency virus using pGEX expression vectors in Escherichia coli. PMID- 1616647 TI - An antitumour necrosis factor therapy. PMID- 1616648 TI - Restriction of serum antibody reactivity to the V3 neutralizing domain of HIV gp120 with progression to AIDS. AB - OBJECTIVE: To identify epitopes on HIV-1 gp120 that correlate with disease resistance and/or prognostic indication. DESIGN: The identification of epitopes on HIV-1 gp120 was determined by testing the reactivity by immunoblotting of anti HIV-positive human sera against partially cleaved Chinese hamster ovary (CHO) cell-derived recombinant gp120. Cleavage of recombinant gp120 occurs in the V3 loop region resulting in 70 and 50K cleavage bands if the protein is subjected to sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. Antibodies reactive with the 120 Mr band alone on immunoblotting indicate that binding is restricted to this cleavage site. Reactivity to either of the cleavage products is independent of gp120 cleavage and indicates that binding occurs in sites other than the V3 cleavage region. METHODS: A panel of anti-HIV-positive human sera was tested for virus neutralizing activity and reactivity by immunoblotting against CHO cell-derived gp120. RESULTS: All sera reacted with the uncleaved from of gp120 but reacted either weakly or did not react with its cleavage products. There was a statistically significant correlation between serum reactivity to cleavage products and clinical stage of disease [Centers for Disease Control (CDC) criteria]. Sera of asymptomatic individuals (CDC stage II/III) were more likely to recognize either one or both of the cleavage products compared with sera from patients presenting with symptoms of disease (CDC stage IV). Furthermore, sera reacting with either one or both of the cleavage products were more likely to have higher neutralizing antibody titres than those that were unreactive. CONCLUSIONS: There is a restriction of serum antibody reactivity (when tested by immunoblotting) to the V3 loop with progression to disease. Raised neutralizing antibody titres may be dependent on regions outside the V3 cleavage site. PMID- 1616649 TI - Isolation and characterization of a new chimpanzee lentivirus (simian immunodeficiency virus isolate cpz-ant) from a wild-captured chimpanzee. AB - OBJECTIVE: To assess the prevalence of infection with simian immunodeficiency virus (SIV) isolate cpz, a lentivirus closely related to HIV-1, in chimpanzees, and to obtain new SIVcpz isolates. METHODS: Forty-four wild-captured chimpanzees in Belgium and Cote d'Ivoire were tested for HIV and SIV antibodies. Virus was isolated from the peripheral blood lymphocytes of positive animals and characterized by electron microscopy, Western blot and radioimmunoprecipitation assay. RESULTS: One animal had antibodies that cross-reacted with HIV-1. A lentivirus was isolated and referred to as SIVcpz-ant. With regard to molecular weight patterns, SIVcpz-ant differs from SIVcpz-gab' an HIV-1-related virus isolated from a wild-captured chimpanzee in Gabon. The major core protein, the transmembrane and outer membrane glycoproteins of the SIVcpz-ant strain consistently had higher molecular weights. Significantly more HIV-1-positive sera reacted with the envelope proteins of the Gabonese SIVcpz-gab strain than with the SIVcpz-ant strain. CONCLUSIONS: This study shows that natural infection of wild-captured chimpanzees with an HIV-related virus may not be uncommon. The diversity of the two chimpanzee isolates, the different geographical origin and the absence of disease suggest that chimpanzees have not recently become SIVcpz infected. PMID- 1616650 TI - Rapid generation of sequence variation during primary HIV-1 infection. AB - OBJECTIVE: HIV-1 undergoes extensive genetic variation in infected individuals. The extent of genetic variation has been examined in patients with AIDS, but little is known regarding the appearance of HIV-1 genetic variation immediately following infection during the primary phase of HIV-1 infection prior to seroconversion. DESIGN: We examined HIV-1 genetic variation during this early phase of HIV-1 infection by polymerase chain reaction (PCR) and nucleotide sequence analysis of the V4 by polymerase chain reaction (PCR) and nucleotide sequence analysis of the V4 variable region and the CD4-binding domain. RESULTS: Our results demonstrate that extensive sequence variation is seen early after infection, although a predominant HIV-1 species is maintained. CONCLUSIONS: The type of variants that occur are dynamic, changing over time, and the mutations seen are consistent with those expected from random occurrence, unlike the pattern of variation previously reported during later stages of disease. PMID- 1616651 TI - Cerebrospinal fluid beta 2-microglobulin in patients with AIDS dementia complex: an expanded series including response to zidovudine treatment. AB - OBJECTIVE: To determine the relationship between cerebrospinal fluid (CSF) beta 2 microglobulin (beta 2M) and severity of AIDS dementia complex (ADC), and between CSF beta 2M and response of ADC to zidovudine. DESIGN: A prospective study. SETTING: Tertiary referral hospital. PATIENTS, PARTICIPANTS: Seventy-eight patients with varying stages of ADC were selected from a subgroup of a cohort of HIV-seropositive patients who are being studied prospectively for the neurological complications of HIV-1 infection. To enter our study, patients had to have an ADC stage of at least 0.5 (equivocal symptoms or abnormal neurological signs in the absence of functional impairment). A control group of 11 HIV-1 seropositive, neurologically normal patients was chosen randomly from the patients followed in the Multicenter AIDS Cohort Study. INTERVENTIONS: Patients were assessed neurologically and neuropsychologically and computed tomography of the brain and CSF studies were performed. MAIN OUTCOME MEASURES: Patients were staged according to severity of ADC on clinical criteria. Neuropsychological test scores were converted to an impairment score. CSF beta 2M was quantified in both serum and CSF of all patients and in 10 patients with pre- and post-zidovudine assessments. RESULTS: There was a high correlation between CSF beta 2M concentration and severity of ADC (P less than 0.0001); treatment with zidovudine significantly reduced these concentrations (P = 0.013). CSF beta 2M concentration was independent of CSF white-cell count and blood-brain barrier impairment. Other CSF changes in the same patients (including blood-brain barrier permeability to albumin, intrathecal synthesis of immunoglobulin G and HIV-1-p24-antigen levels) were less useful as objective correlates of ADC severity and response to zidovudine therapy. CONCLUSIONS: CSF beta 2M may be a valuable marker of ADC severity and response to antiviral therapy. PMID- 1616652 TI - The spectrum of clinical and pathological manifestations of AIDS in a consecutive series of autopsied patients in Mexico. AB - OBJECTIVE: Little is known about the clinical profile of AIDS in Latin American populations. This study characterizes the clinical and pathological manifestations of AIDS in a representative series of Mexican AIDS patients at autopsy. DESIGN: The clinical and pathological findings were abstracted retrospectively for a sequential series of autopsied AIDS patients. SETTING: Autopsies were conducted at the four major tertiary level hospitals that serve the majority of AIDS patients in Mexico City. PATIENTS: Subjects included 177 consecutive patients diagnosed with AIDS between March 1984 and January 1989 who subsequently died and were autopsied in the same period in the study hospitals. MAIN OUTCOME MEASURES: Demographic characteristics, including age, gender, residence, socioeconomic status, and risk group; clinical presentation and autopsy findings, including opportunistic infections and malignancies. RESULTS: Sixty per cent of the AIDS patients presented with wasting syndrome. The most common infections were cytomegalovirus (69%), tuberculosis (25%), and Pneumocystis carinii pneumonia (24%). Central nervous system infections were also common and included toxoplasmosis (19%) and cryptococcoses (10%). Kaposi's sarcoma was present in 30% of cases and non-Hodgkin's lymphoma in 9%. CONCLUSION: Clinical manifestation, and types and frequency of opportunistic infections in our Mexican AIDS patients were more similar to those seen in AIDS patients in Africa and Haiti than in the United States and Europe. These findings suggest that the AIDS epidemic in Mexico has an 'intermediate' pattern and may be a prototype for Latin American countries. PMID- 1616653 TI - Patterns and predictors of high-risk sexual behavior in female partners of HIV infected men with hemophilia. AB - OBJECTIVE: To characterize and quantify high-risk heterosexual activity in HIV discordant couples. DESIGN: Analysis of cross-sectional and longitudinal questionnaire data from 217 HIV-negative female sexual partners of HIV-infected hemophilic men. METHODS: Comparison of prevalence rates of anal sex, oral sex, vaginal intercourse with or without condoms, and use of other contraceptives between 1985 and 1991. Logistic regression analysis of demographic, sexual and clinical variables to predict unprotected vaginal sex. Actuarial estimates of semi-annual relapse rates to unsafe sex. RESULTS: The proportion of women at low risk increased from 7 to 69% between 1985 and 1991, mainly because more women were using condoms during all acts of vaginal intercourse. Other contraceptive practices did not change during this time. The proportion engaging in oral or anal sex decreased (from 26 to 13% and 13 to 4%, respectively). Unprotected vaginal sex was more common among women who enrolled earlier, had less education, engaged in oral or anal sex, and among those whose partners had not had AIDS. Unprotected vaginal sex before enrollment was the strongest predictor of this high-risk activity during follow-up. Two-year rates of relapse to high-risk behavior were significantly higher among women who enrolled at high risk compared with those who enrolled at low risk (39 versus 8%, P = 0.005). CONCLUSIONS: Although high-risk sexual behavior became much less prevalent in this population between 1985 and 1991, many continued to have unprotected vaginal sex occasionally. Counseling efforts should target couples who have been the most sexually active or have less education, and should emphasize not only initial risk reduction but also maintenance of low-risk behavior. PMID- 1616654 TI - Determinants of survival in adult Brazilian AIDS patients, 1982-1989. The Brazilian State AIDS Program Co-Ordinators. AB - OBJECTIVE: Little has been published about the length and determinants of survival for persons with AIDS in developing countries. This study examined the survival experience of Brazilian AIDS patients from 1982 to 1989. DESIGN: A retrospective cohort study involving record review of reported AIDS cases. METHODS: We obtained information about 2135 adult AIDS patients in Brazil. Local health officials supplied data regarding demographic and clinical characteristics and length of survival. Statistical techniques of survival analysis were applied. RESULTS: Median survival was 5.1 months, much shorter than in developed countries, and there was no improvement in survival for cases diagnosed more recently. Younger patients and those in the intravenous drug use exposure category lived longer than other AIDS patients. Those presenting with Kaposi's sarcoma, esophageal candidiasis, and tuberculosis fared relatively well, while those presenting with multiple diagnoses or toxoplasmosis did more poorly. CONCLUSIONS: These results tend to confirm the predictors of AIDS survival previously reported from developed countries and to document the poor survival of AIDS patients in the developing world. PMID- 1616655 TI - Association between HIV-2 infection and genital ulcer diseases among male sexually transmitted disease patients in The Gambia. AB - OBJECTIVE: To investigate whether genital ulcer diseases are cofactors which enhance the transmission of HIV-2 in West Africa. DESIGN: A cross-sectional study of 435 men presenting with a sexually transmitted disease (STD). SETTING: The outpatient clinic of the Medical Research Council Laboratories, a primary care facility in Fajara, a suburb of Banjul, the capital city of The Gambia (West Africa). PATIENTS, PARTICIPANTS: Six hundred and twenty-four men presenting with a genital complaint, of whom 443 had an STD. Eight of the men with an STD were excluded from further analysis because they were HIV-1-infected (five patients) or had indeterminate Western blot patterns (three patients). The remaining 21 HIV 2-infected and 414 seronegative men constituted our study-group. MAIN OUTCOME MEASURES: Participants were questioned about previous STD and behavioural and demographic characteristics. A physical examination was performed and serum collected for measurement of antibodies against Haemophilus ducreyi and Treponema pallidum. RESULTS: HIV-2-infected men were more likely than HIV-seronegative participants to have previously had a genital ulcer [odds ratio (OR), 3.00; 95% confidence interval (Cl), 1.18-7.60] and to have antibodies against T. pallidum (OR, 5.95; 95% Cl, 2.10-16.91), or H. ducreyi (OR, 4.59; 95% Cl, 1.71-12.33). Circumcised patients with residual foreskin were more likely to be HIV-2 infected than patients with complete circumcision. HIV-2-seropositive patients were six times more likely to have generalized lymphadenopathy than their seronegative counterparts. CONCLUSIONS: Our data suggest that genital ulcerative diseases, such as syphilis and chancroid, are probably cofactors that increase the transmission of HIV-2 in West Africa, and that HIV-2 infection frequently results in generalized lymphadenopathy. PMID- 1616656 TI - A system for surveillance of voluntary HIV testing: results of the first 2 years, 1989-1990. AB - OBJECTIVE: In 1988, in order to improve the already established surveillance of AIDS and HIV-infected cases in Scotland, UK, the Communicable Diseases (Scotland) Unit [CD(S)U], in collaboration with microbiologists responsible for HIV testing, instituted a routine system for the epidemiological surveillance of all voluntary HIV tests. METHODS: To facilitate information capture, a standardized HIV request form was introduced for use throughout the country by clinicians requesting an HIV test. In addition, a network of laboratory computers, operated by clerical personnel, was established for the collection and collation of data. RESULTS: In 1989, of 9483 individuals tested for HIV, 129 (1.4%) were HIV-antibody-positive compared with 130 (1.2%) of 11,111 tested in 1990. A comparison of 1989 with 1990 rates of HIV among specific population groups, including injecting drug users (4.1%, 1989; 2.7%, 1990), homosexual men (5.2%, 1989; 4.5%, 1990), heterosexual men and women with high-risk partners (1.6%, 1989; 1.8%, 1990) and heterosexual men and women with lesser risk (0.3%, 1989; 0.5%, 1990), revealed no statistically significance differences at a 95% level of confidence. CONCLUSION: We believe that this surveillance system is the first of its kind to be implemented on a nationwide basis. The first 2 years' findings suggest a degree of stability in new transmissions of HIV occurring in Scotland. However, the increasing numbers of those known to be HIV-infected continue to cause considerable concern: 1943 individuals were reported to CD(S)U as HIV-antibody positive by December 1991. PMID- 1616657 TI - The low rate of HIV infection in Japanese homosexual and bisexual men: an analysis of HIV seroprevalence and behavioural risk factors. AB - OBJECTIVE: To assess the seroprevalence of HIV-1 infection in homosexual and bisexual men in Nagoya City, Japan. DESIGN: A prospective study ongoing since April 1986. METHODS: Nine hundred and thirty-eight serum samples were collected from 531 participants in August 1990 in an anonymous, confidential testing programme. A self-administered questionnaire was completed and all participants anonymized by a code number. Interviews were conducted and HIV-antibody test results given by telephone, except for the positive test results, which were given in person and counselling offered. RESULTS: Two out of the 531 participants (0.38%) were found to be seropositive for HIV-1, although the seroprevalences of sexually transmitted diseases, including hepatitis B, syphilis, chlamydia infection and amoebiasis, were remarkably high. A small number of participants had had sexual contact with individuals from countries where HIV infection rates are high. No patient had had a recent episode of intravenous drug use. Numbers of male sexual partners were decreasing and unsafe sexual practices, such as anal intercourse without condom use, were also decreasing. CONCLUSIONS: The apparent low-risk behaviour of the men studied here (low levels of sexual contact with foreigners, absence of intravenous drug use, decreasing numbers of sexual partners and unsafe sexual practices) may explain the low prevalence of HIV infection. PMID- 1616658 TI - Association between HTLV-1 and HIV-2 infections in Bissau, Guinea-Bissau. PMID- 1616659 TI - Efficacy of octreotide in the management of chronic diarrhoea in AIDS. PMID- 1616660 TI - Clinical implications of recovery of Mycobacterium avium complex from the stool or respiratory tract of HIV-infected individuals. PMID- 1616661 TI - Refusal of zidovudine by HIV-positive patients. PMID- 1616662 TI - The importance of multisite sampling in determining the prevalence of HIV among drug injectors in Glasgow and London. PMID- 1616663 TI - Update: epidemiology of reported cases of AIDS in women who report sex only with other women, United States, 1980-1991. PMID- 1616664 TI - High frequency of antibodies against recombinant HIV-2 Nef protein in HIV-2 positive and HIV-negative sera. PMID- 1616665 TI - Decline in immunoglobulins associated with AIDS-related biliary disease. PMID- 1616666 TI - Role of major histocompatibility complex recognition in the protection and immunopathogenesis of AIDS. Joint Anglo-Italian Workshop on Ponza Island, Italy. PMID- 1616668 TI - Community concerns. PMID- 1616667 TI - The coming of Euronurse. PMID- 1616669 TI - Care in the country. PMID- 1616670 TI - Keeping the pressure off. PMID- 1616671 TI - Change in practice. PMID- 1616672 TI - Communication and care. PMID- 1616673 TI - Travesties of care. PMID- 1616675 TI - Managing residential care. PMID- 1616674 TI - Postural hypotension. PMID- 1616676 TI - On the campaign trail. PMID- 1616678 TI - Home help in Korea. PMID- 1616677 TI - ACE matters. PMID- 1616679 TI - Breaking down. PMID- 1616681 TI - A credit to the Open University. PMID- 1616680 TI - RCN nursing update. PMID- 1616682 TI - Fever of unknown origin. AB - FUO is an uncommon problem in pediatric patients if one uses a strict definition of at least 2 weeks of fever. Perhaps the best definition, as suggested by Lorin and Feigin, is more than 1 week of fever and a negative initial evaluation, including examination and preliminary laboratory results. Most patients, especially younger ones, will spontaneously improve or have common disorders, usually respiratory-related infections. Most patients will have uncommon manifestations of more commonly recognized disorders. Mortality rates, even in those series that include a week in the hospital without a diagnosis, are 15% to 20% at maximum--half that seen in most series of adult patients. Common mistakes are failure to document fever, failure to perform a complete history or physical examination, a shotgun approach that uses the laboratory to make diagnoses, and overuse or inappropriate use of newer imaging techniques in an undirected fashion. Patience, persistence, repeated histories and physical examinations, and continued observation offer the best chance of making a diagnosis in difficult cases. In the current decade, we continue to learn about new manifestations of old disorders--cat-scratch disease, Kawasaki disease, neonatal syphilis, and Epstein-Barr virus infection are examples. The use of older and well-established methods (history and physical examination) and the addition of newer techniques (ultrasound, CT, MRI, etc.) to pursue suggested diagnoses offer the best current approaches to the patient with prolonged and unexplained fever. PMID- 1616683 TI - Nontuberculous mycobacterial infections in children. PMID- 1616684 TI - Congenital syphilis. PMID- 1616685 TI - Infectious complications of solid-organ transplantation in children. PMID- 1616686 TI - Neonatal sepsis. PMID- 1616687 TI - The chronic fatigue syndrome: considerations relevant to children and adolescents. PMID- 1616688 TI - Uses of intravenous globulin to prevent or treat infections. PMID- 1616689 TI - Crystallization and preliminary crystallographic data for the azurin mutant Ala 114 from Pseudomonas aeruginosa. AB - The site-specific mutant alanine 114 of the blue copper protein azurin from Pseudomonas aeruginosa in Escherichia coli has been crystallized from PEG 4000 in a new crystal form compared to the wild type utilizing the hanging-drop procedure. The crystals are blue well-formed prisms. Monoclinic, P2(1), a = 51.03 (5), b = 83.36 (5), c = 66.30 (6) A and beta = 111.0 (1) degrees. 14,875 reflections up to 2.7 A have been collected using a modified Syntex P2(1) automated four-circle diffractometer. PMID- 1616690 TI - Preliminary crystallographic study of peanut peroxidase. AB - The cationic isozyme of peroxidase isolated from suspension cultures of peanut cells is a heme-containing and calcium-dependent glycoprotein having four covalently attached oligosaccharide chains. Attempts were made to crystallize the glycoprotein for X-ray diffraction analysis, and these have met with some success. Crystals have now been grown that are suitable for a full three dimensional structural analysis. The crystals are thin plates and we have shown them to be of the orthorhombic space group P2(1)2(1)2(1) with a = 48.1, b = 97.2, c = 146.2 A. The crystals diffract to beyond 2.8 A resolution, appear to be stable to lengthy X-ray exposure, and contain two molecules of 40,000 daltons each in the asymmetric unit. PMID- 1616691 TI - Location of the sulfur atoms from the phased anomalous map using native protein data can be very helpful in tracing the peptide chain. PMID- 1616692 TI - Refinement of rubredoxin from Desulfovibrio vulgaris at 1.0 A with and without restraints. AB - X-ray data have been recorded from crystals of rubredoxin derived from the bacterium Desulfovibrio vulgaris to a resolution of 1.0 A using in part synchrotron radiation and in part X-rays from a sealed-tube Mo K alpha source. In both cases an imaging-plate scanner was used as detector. The space group of the crystals is P2(1) with cell dimensions a = 19.97, b = 41.45, c = 24.41 A and beta = 108.3 degrees. The overall merging R(I) factor between symmetry-related reflections was 5.8%. The model was refined by least-squares minimization initially with stereochemical restraints to an R factor of 16.4%. Only atomic positional parameters and isotropic temperature factors for non-H atoms were used in the refinement. There were 18,532 independent X-ray observations for a total of 1916 atomic parameters. A round of unrestrained refinement gave an R factor of 16.0%, acceptable geometry for more than 90% of the protein atoms, but emphasized the disorder inherent in eight of the residues. A final round of restrained refinement gave an R factor of 14.7%. Three of the 389 protein atoms in the molecule, in the side chain of Lys2, have been assigned zero occupancy in the model. A total of eight atoms in three side chains have been assigned two conformations, giving 393 protein atomic sites in the model. In addition there is one Fe atom, a sulfate ion and 102 water sites. 339 H atoms were included at their calculated positions, which were not refined. There is clear evidence for anisotropic thermal motion. This has not been incorporated in the present model. PMID- 1616693 TI - The segmented anisotropic refinement of monoclinic papain by the application of the rigid-body TLS model and comparison to bovine ribonuclease A. AB - The anisotropic displacements of selected rigid groups in monoclinic papain have been refined from X-ray diffraction data by application of the rigid-body TLS model. The rigid groups chosen were the aromatic side chains of tryptophan, tyrosine, histidine and phenylalanine, and the planar carboxylic and guanidinium side chains of aspartic acid, glutamic acid, glutamine, asparagine and arginine. The derived translation and libration tensors have been compared with those previously derived for bovine ribonuclease A and provide evidence for different modes and anisotropies of displacement over the two proteins. PMID- 1616695 TI - Wisconsin's Disaster Identification team helps set the pace for other states. PMID- 1616694 TI - Structure determination of monoclinic canine parvovirus. AB - The three-dimensional structure of the single-stranded DNA canine parvovirus has been determined to 3.25 A resolution. Monoclinic crystals belonging to space group P2(1) (a = 263.1, b = 348.9, c = 267.2 A, beta = 90.82 degrees) were selected for data collection using primarily the Cornell High Energy Synchrotron Source and oscillation photography. There was one icosahedral particle per crystallographic asymmetric unit, giving 60-fold redundancy. The particle orientations in the unit cell were determined with a rotation function. The rough positions of the particles in the unit cell were estimated by considering the packing of spheres into the P2(1) crystal cell. More accurate particle centers were determined from Harker peaks in a Patterson function. Hollow-shell models were used to compute phases to 20 A resolution. The radii of the models were based on packing considerations, the fit of spherical shells to the low resolution X-ray data and low-angle solution scattering data. The phases were extended to 9 A resolution using molecular replacement real-space averaging. These were then used to determine the heavy-atom position of a K2PtBr6 derivative, for which only 5% of the theoretically observable reflections had been recorded. The center of gravity of the 60 independent heavy-atom sites gave an improved particle center position. Single isomorphous replacement phases to 8 A resolution were then calculated with the platinum derivative. These were used to initiate phase improvement and extension to 3.25 A resolution using density averaging and Fourier back-transformation in steps of one reciprocal lattice point at a time. The resulting electron density map was readily interpretable and an atomic model was built into the electron density map on a PS390 graphics system using the FRODO program. The R factor prior to structure refinement for data between 5.0 and 3.25 A was 36%. PMID- 1616696 TI - Bite mark evidence contributes to the criminal justice system. PMID- 1616697 TI - Yellow Pages advertising. PMID- 1616698 TI - Got the UCR blues? What to do when insurance companies tell your patients your fees are over the usual and customary. PMID- 1616699 TI - The rising cost of healthcare--why? PMID- 1616700 TI - Loading and transfer control for Northern hybridization. AB - We report a simple and inexpensive method to quantitate loading and transfer of RNA and to examine RNA integrity for use with Northern hybridization. This technique involves quantitation by computer-assisted video densitometry of a negative photograph of 28S and 18S rRNA from ethidium bromide-stained RNA fixed to nylon membranes. This method eliminates the issue of variability of expression of "housekeeping" genes and the need for a second round of hybridization to quantitate control probes. PMID- 1616701 TI - A sensitive microplate assay for glycoproteins that utilizes an immunological digoxigenin-based detection system. AB - A sensitive microplate assay for glycoproteins, based on an immunological digoxigenin-based detection system, is described. When log absorbance was plotted against log concentration, linear standard curves were obtained over the range 25 ng/ml to 25 microliters/ml with bovine submaxillary mucin, porcine stomach mucin, fetal calf fetuin, asialofetuin and human transferrin. This detection limit and range are far superior to other assays that have been described. The use of the microtiter plate format means that a large number of samples can be assayed with ease. Due to the broad range of the assay, the concentration of the sample is not a particular problem, and samples above the upper cutoff value can be serially diluted in the microtiter plate to find an appropriate value. PMID- 1616702 TI - Efficient production of single-stranded DNA as long as 2 kb for sequencing of PCR amplified DNA. AB - A modification of the asymmetric PCR method is described, which reliably facilitates sequencing of PCR-amplified DNA. This procedure produces single stranded DNA fragments as long as two kilobases that are suitable for dideoxy DNA sequencing. First, a PCR for double-stranded DNA is preformed under optimal conditions (double-stranded PCR). Then, a 5-10-microliters fraction of the double stranded PCR and a single primer are used to generate single-stranded DNA in a separate PCR (single-stranded PCR). The concentration of the single primer are used to generate single-stranded DNA in a separate PCR (single-stranded PCR). The concentration of the single primer is approximately 0.4 microM. Usually 15 to 25 cycles of single-stranded PCR are optimal to produce single-stranded DNA for four to eight sequencing reactions. The single-stranded DNA is purified by centrifugal ultrafiltration and used directly in dideoxy sequencing. This method was employed to produce high-quality single-stranded DNA templates from a variety of organisms for efficient DNA sequencing of PCR-amplified DNA. PMID- 1616703 TI - A rapid method for cosmid cloning. AB - We present a method for genomic library construction using cosmid vectors. With a combination of backfilling with Klenow enzyme and a cosmid vector with two cos sites, a DNA bank in excess of 500,000 clones can be made from 10 micrograms of genomic DNA. The method is more rapid than conventional protocols because size fractionation of target DNA is not necessary. A further advantage is that libraries can be made from relatively small amounts of genomic DNA. PMID- 1616704 TI - Magnesium chelation inactivates beta-galactosidase in -20 degrees C storage. AB - Mammalian cell lysate containing beta-galactosidase (beta Gal) derived from the transient expression of the bacterial lacZ gene driven by the human beta-actin promoter loses activity progressively over time in storage at -20 degrees C in the presence of EDTA. The simultaneous presence of NaCl with EDTA exacerbates such an inactivation, although NaCl by itself does not. However, EGTA, a chelating agent that preferentially binds Ca2+ over Mg2+, does not inactivate beta Gal. Addition of equal or higher molar concentration of Mg2+ (as MgCl2) or Ca2+ (as CaCl2), both effectively chelated by EDTA, to an EDTA-containing lysate prevents this cold-related inactivation, but does not reactivate the enzyme. Therefore, the chelation of Mg2+ by EDTA at -20 degrees C inactivates beta Gal. Storage of cell lysate at -70 degrees C completely prevents the EDTA-induced inactivation of beta Gal. It is recommended that when beta Gal activity is used as the reporter for gene expression 1) EDTA should not be used to prepare cell lysate and 2) the cell lysate should be stored in a -70 degrees C freezer to preserve full activity. PMID- 1616705 TI - Application of the chloramphenicol acetyltransferase (CAT) diffusion assay to transgenic plant tissues. AB - Chloramphenicol acetyltransferase (CAT) activity was quantified in crude extracts from tobacco callus tissues using a modification of a previously reported diffusion assay. We describe here the alterations necessary in applying this rapid and simple assay procedure to plant materials. Due to the high concentration of nonspecific oxidases present in most plant tissues, some type of protective agent is required to maintain enzyme activity. We have tested beta mercaptoethanol, cysteine, dithiothreitol, ascorbic acid and polyvinyl pyrrolidone as protective agents within the initial extraction buffer. We also investigated the effect of heat (60 degrees C, 10 min) and 5 mM EDTA on CAT activity. The highest CAT activity was obtained using 5 mM cysteine plus 5 mM EDTA in 40 mM Tris-HCl (pH 7.8) as the initial extraction buffer followed by a heat treatment. Using this buffer, CAT activity was stable on ice for more than two hours. In our hands, total acetyl-coenzyme A concentration within the assay mixture was found to be saturating at 250 microM and the Km determined to be 100 microM. Assays performed using the same crude plant extract indicate that 1) duplicate assays show less than 1.5% variation in activities and 2) CAT activity increases linearly with respect to volume of extract used. PMID- 1616706 TI - Separation and purification of high molecular weight glycoproteins using agarose gel electrophoresis. AB - Several components of the extracellular matrix in the molecular weight range of 220 kDa to 150 kDa were purified by preparative electrophoresis on 2.5% Pro-Sieve agarose gels. These high molecular weight glycoproteins, separated under reducing conditions, were recovered in solution by extraction of individual agarose gel slices and analyzed on sodium dodecyl sulfate polyacrylamide gels and Western blots. This simple method permitted the separation and recovery of the laminin B chains (220 kDa and 205 kDa) and entactin (150 kDa) and may prove useful for the purification of other high molecular weight species. PMID- 1616707 TI - Effect of DNA concentration on recombinant plasmid recovery after blunt-end ligation. AB - We describe conditions for optimal recovery of recombinant plasmids after blunt end ligation. It was found that one of the most critical parameters of the blunt end ligation reaction is total DNA concentration (vector plus incoming DNA). This concentration was optimal in the range of 1-5 micrograms/ml of reaction mixture. Concentrations larger than 10 micrograms/ml result in strong inhibition. The optimal molar relationship between incoming DNA and vector was found to be 1 or less. Under these conditions, using dephosphorylated vector, recombinants are generated at a frequency of 10(6) colonies per microgram of insert, provided that transforming efficiency is about 5 x 10(7) colonies per microgram of plasmid DNA. PMID- 1616708 TI - Direct microtiter plate sequencing of PCR-amplified M13 clones from plaques using dried reagents. AB - A method is described using dried reagents in microtiter plates for direct PCR and sequencing of M13 plaques. The method has advantages of reliability and high throughput that make it suitable for medium to large-scale sequencing projects. PMID- 1616709 TI - Methods to identify and avoid artifactual formation of interchain disulfide bonds when analyzing proteins by SDS-PAGE. AB - Amicyanin is a monomeric protein of known structure which possesses a single cysteine that serves as a ligand to copper in its native state. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of amicyanin after denaturation in the presence and absence of beta-mercaptoethanol, however, indicated that this protein was a dimer which was covalently linked by interchain disulfide bonds. This artifact was caused by exposure during denaturation of the free cysteine that normally binds copper and subsequent formation of a disulfide bond between otherwise unliked monomers. This phenomenon is documented, and additional control experiments are proposed to identify and avoid this artifact when using SDS-PAGE to analyze the subunit structure of proteins. PMID- 1616710 TI - A hemagglutinating substance in chitin. AB - Chitin from crustacean shells has often been used to isolate and purify plant lectins that have an affinity for poly-N-acetylglucosamine (poly-GlcNAc). When we used washed chitin from crab shells as an affinity medium to isolate a lectin from Pinus strobus L. (eastern white pine) ovules, we found that a substance having a strong capacity to agglutinate red blood cells was eluted from the chitin during a weak acid desorption step. The chitin agglutinin is a complex structure containing protein and poly-GlcNAc. Chitin samples from four biochemical suppliers were tested; all contained the elutable agglutinin. Acid (0.05 N HCl or 0.1 N acetic acid) appears to hydrolyze the material from the solid chitin. NaOH at 0.5 N does not remove the agglutinin. Since agglutination is the assay used to monitor lectin purification, care must be taken to avoid the native agglutinin if chitin is used as an affinity matrix. PMID- 1616711 TI - Combinative oligonucleotide-directed large deletions as a strategy for surveying the regulatory region of a gene. PMID- 1616712 TI - Increasing DNA synthesizer throughput via off-instrument cleavage and deprotection. PMID- 1616713 TI - A rapid method for preparation of bacterial chromosomal DNA in agarose plugs using Thermus Rt41A proteinase. PMID- 1616714 TI - Efficient measurement of radioactivity in oligonucleotides. PMID- 1616715 TI - A rapid and efficient protocol for sequencing plasmid DNA. PMID- 1616716 TI - An improved enzyme-linked immunoadsorbent assay for the detection of antibodies to galactocerebroside. PMID- 1616717 TI - One reagent simultaneously identifies the salt and the protein peaks on desalting column. PMID- 1616718 TI - A modified procedure for replica plating of mammalian cells allowing selection of clones based on gene expression. AB - The polyester cloth replica-plating technique for selection of mammalian cell clones was modified by growing cells in colonies on a flexible polytetrafluoroethylene membrane and then transferring them completely to polyester cloth (27-microns mesh), from which a replica was made by allowing cells to transfer to a cloth of smaller pore size (17-microns mesh). Using this technique, two phenotype selection methods are demonstrated here: in situ hybridization for detection of a specific mRNA and a photographic film assay for detection of luciferase expression. Cells were transfected with pSV2AL-A delta 5' in which firefly luciferase cDNA is under the control of the simian virus 40 promoter. The luciferase assay was adapted for colonies on polyester cloth; cells were permeabilized with digitonin to allow access of ATP and luciferin to the cell without disruption of colonies. Clones selected for expression or nonexpression of luciferase by the photographic film assay were positive or negative for expression after isolation from the cloth replica and subsequent growth under conventional culture conditions. The replica-plating procedure described here should be generally applicable to most mammalian cell types. The ability to produce replicas of colonies, combined with in situ hybridization or assays that can be adapted to in situ detection, provides phenotype selection for clones based on gene expression independent of growth characteristics. PMID- 1616719 TI - A new deficiency mapping technique using the SOFI detector. AB - We present a new technique for chromosomal deficiency mapping that takes advantage of the ability of the SOFI detector to provide fast quantitative data of very weak signals. With this new strategy, in contrast to the time-consuming traditional method, all the clones corresponding to a given genomic region may be mapped for their inclusion inside a deletion with only two hybridizations, independent of the size of the genomic region to be analyzed. PMID- 1616720 TI - Use of perfluorocarbon emulsions in cell culture. AB - Perfluorocarbon emulsions were applied to hybridoma cultures grown in tissue culture tubes and column bioreactors. The oxygen transfer enhancement effect of perfluorocarbon emulsions was clearly demonstrated by the higher cell densities obtained in emulsion-supplemented systems. In addition, perfluorocarbon emulsions were shown to provide better cell suspension in a low-shear environment. The study in column bioreactors also suggested a cell protective effect of the employed perfluorocarbon emulsions in reducing the damage to cells by gas bubbles. PMID- 1616721 TI - DNA hybridization assay using ATTOPHOS, a fluorescent substrate for alkaline phosphatase. AB - A fluorometric procedure for the detection of DNA-DNA hybrids is described. The procedure involved the detection of probe-bound alkaline phosphatase with the fluorescent substrate ATTOPHOS. This substrate is converted to ATTOFLUOR by alkaline phosphatase and fluoresces strongly at 550 nm when excited with a wavelength of 440 nm. DNA hybridization assays were performed both with dilutions of purified target plasmid DNA (pSE9 or PBR322) and whole bacterial cells. Streptavidin-alkaline phosphatase conjugates were added to react with bound probe. Fluorometric assays, as well as colorimetric assays, using 5-bromo-4 chloro-3-indolylphosphate + nitroblue tetrazolium for alkaline phosphatase activity were performed. The fluorescence of the substrate was measured at time intervals, and the slope of the regression line calculated. A slope four times greater than that of background was considered positive. One hundred femtograms or 2.2 x 10(4) molecules of homologous DNA were detected with the fluorescent assay as compared with 10,000 femtograms or 2.2 x 10(6) molecules of homologous DNA with the colorimetric assay. Similar results were obtained with whole cells. Approximately 1 x 10(3) homologous cells were detected fluorometrically and 1 x 10(5) cells were detected colorimetrically. Based on these results, we conclude that, in our hands, the DNA hybridization assay described here using ATTOPHOS as the substrate for alkaline phosphatase is a very sensitive assay for the detection of DNA-DNA hybrids. PMID- 1616722 TI - HIV-1 infection and cardiothoracic surgery: the difference in attitudes between consultants and junior surgeons in the United Kingdom. AB - A postal survey was carried out inviting the opinions of consultant and trainee cardiothoracic surgeons on the subject of operating upon patients who are either HIV-1 antibody positive or suffer from full-blown AIDS. The questionnaire contained both cardiac and thoracic clinical situations, all of which under normal circumstances would be managed surgically with low operative mortality and long median survival. The overall response rate was 72.4%. A significantly greater number of consultants replied compared to juniors, 80% and 51.6%, respectively (P less than 0.001). In both groups, surgeons were more likely to operate upon a patient who was HIV-1 antibody positive than one who had AIDS. There were no significant differences in the replies of consultants and juniors to the clinical scenarios presented. However, a greater number of juniors admitted to modifying their surgical practice in the light of the increasing incidence of HIV-1 infection (P less than 0.001). Routine preoperative HIV antibody testing was advocated by 77.8% of consultants and 75% of juniors and this rose to 95.1% and 97%, respectively, if patients were in the traditionally high risk groups. Four consultants admitted that they were already performing routine preoperative HIV antibody screening. This survey emphasized the real concern amongst cardiothoracic surgeons, irrespective of their grade, about HIV-1 infection and the need for both education and clear policy guidelines to deal with this difficult issue. PMID- 1616723 TI - Blunt chest injuries in 1696 patients. AB - We review 1696 patients with blunt chest trauma. Road traffic accidents were the main cause of injury followed by domestic falls and labour accidents. Outdoor falls and sport accidents accounted for a small number of injuries. For clinical evaluation, Stoddart's score was used. The injuries were considered as minor in 710 patients, intermediate in 740 and severe in 246. Global in-hospital mortality was low (5%) but increased to 37% when only patients with multiple severe injuries were considered. Thoracic wall fractures were present in 1419 patients. Flail chest was diagnosed in 140 patients and pulmonary contusion in 275. Diaphragmatic rupture was present in 40 patients and tracheobronchial injury in 6. Cardiovascular injuries occurred in 55 patients. Associated extrathoracic injuries were seen in 611 patients: 923 patients were clinically observed and/or medically treated. An intercostal tube was inserted in 638 patients. Thoracotomy was undertaken in 105 patients. Surgical fixation for flail chest was carried out in 29 patients. The results were generally good: 9 patients did not need any mechanical ventilation and 11 were ventilated for a short period. No deaths were due to the surgical procedure. The authors maintain that a selective attitude restricting, but not ignoring, surgical stabilization is the best policy. PMID- 1616724 TI - Evaluation and treatment of secondary tricuspid insufficiency. AB - To define the role of functional tricuspid insufficiency and right ventricular (RV) failure in patients with mitral disease, the data of 121 patients with secondary tricuspid insufficiency that underwent mitral valve replacement (MVR) from January 1982 to December 1987 were analyzed. The mitral hemodynamic lesion was: stenosis in 41 patients (33.9%); insufficiency in 11 (9.1%) and mixed stenosis and insufficiency in 69 (57.0%). NYHA functional class was: II in 4 patients (3.3%), III in 78 (64.5%) and IV in 39 (32.2%). In 100 cases (group 1) with tricuspid insufficiency defined as moderate or severe, a De Vega annuloplasty was performed while in 21 (group 2) with mild tricuspid insufficiency, no tricuspid surgical procedure was performed. Hospital deaths occurred in 17 of 121 patients [14% (CL 10.8-17.0)]. There was no significant difference in hospital mortality between group 1 and group 2 (15% vs 9.5%; P = 0.75). Incremental risk factors for hospital mortality as determined by multivariate analysis, include: cardiothoracic ratio (P = 0.0016), total aortic cross-clamp time (P = 0.006), associated cardiac disease (P = 0.0209) and emergency operations (P = 0.0318). Mean follow-up of surviving patients was 50.1 +/- 28.1 months. Late deaths occurred in 16 patients [15.4% (CL 11.7-18.7)]. The actuarial survival rate was 85.6% and 73.8% at 5 and 9 years, respectively. Nine patients [8.6% (CL 5.9-11.3)] required reoperation. There was no significant difference between group 1 and group 2 in the rate of late cardiac related deaths (5.9% vs 5.3%, P = 0.66) and of tricuspid reoperations (4.7% vs 5.3%, P = 0.62).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616726 TI - Effect of differing acid-base regulation on cerebral blood flow autoregulation during cardiopulmonary bypass. AB - Cerebral dysfunction following cardiopulmonary bypass may be aggravated by altered autoregulation of cerebral blood flow. We have used trans-cranial Doppler to measure middle cerebral artery blood flow velocity during cardiopulmonary bypass managed by either pH-stat or alpha-stat acid-base protocols. Fourteen patients were studied, 7 in each group. During bypass at 28 degrees C, patients underwent incremental alterations in mean arterial pressure from 20-90 mmHg, maintaining systemic perfusion flow at 1.75 L/min per m2. The cerebral extraction ratio of oxygen was measured to indicate matching of cerebral blood flow to demand. The pH-stat group showed a pressure passive cerebral circulation with significant (r = 0.999, P less than 0.05) increase in blood flow velocity with increasing arterial pressure. This also occurred in alpha-stat group during the pressure range of 20-50 mmHg (r = 0.951, P less than 0.05). During the pressure range of 50-90 mmHg in alpha-stat group the change in flow velocity (0.16 cm/sec per mmHg) was significantly (P less than 0.05) less than that in pH-stat group (0.58 cm/second per mmHg). The cerebral extraction ratio of oxygen was less depressed in the alpha-stat group than in the pH-stat group, indicating more appropriate matching of cerebral blood flow and tissue demand. These results suggest that, during alpha-stat managed cardiopulmonary bypass, cerebral blood flow velocity is less subject to wide pressure alteration than pH-stat. PMID- 1616725 TI - Clinical experience of mitral valve reconstruction with artificial chordae implantation. AB - To expand the application of mitral valve reconstruction for pure mitral regurgitation due to diffuse leaflet prolapse, we have employed artificial chordae implantation using GPEP strips in 9 patients and 4-0 PTFE sutures in 20 patients since November 1986. The total number of GPEP strips implanted was 20 with a range from 1 to 4 (average 2.2 per patient) and 45 pairs of PTFE sutures with a range from 1 to 6 (average 2.3 per patient). There was one hospital death (3.4%). All other patients survived operation without valve-related complications except 1 patient who required reoperation for failure of mitral valve reconstruction. In 27 survivors free from reoperation, the amount of mitral regurgitation assessed postoperatively was none or trivial in 19 patients, mild in 7 and moderate in 1. All 27 patients improved to NYHA functional class I or II. So far, our results were no less acceptable than those with conventional procedures for mitral valve prolapse. PMID- 1616727 TI - Minimisation of priming volume and blood saving in paediatric cardiac surgery. AB - We started a programme of donor blood reduction for open heart surgery in children in 1983. At first, only meticulous surgical and perfusion techniques were used. Later, increased haemodilution was added. Miniaturisation of the perfusion circuit and introduction of blood taken prior from the patient further decreased donor blood requirements. In 1989, we used 0.89 l per patient compared to 3.2 l per patient in 1983. Miniaturisation of the circuit was tested in a pilot study on 30 children undergoing the Senning operation in 1988. Priming volume was reduced from 661 +/- 72 ml to 421 +/- 62 ml. In 1989, 167 out of 194 children (86%) received a clear prime. Ninety-seven of 100 children whose weight was over 15 kg received a clear prime: 55 did not require subsequent transfusion. Prime miniaturisation and autotransfusion can considerably reduce blood requirements for open heart surgery. PMID- 1616728 TI - Pectus excavatum. A clinical study with long-term postoperative follow-up. AB - Between 1972 and 1987, 192 patients have been operated upon for pectus excavatum of which 152 patients were included in the study (79%). Mean age at operation was 15.3 +/- 5.5 years; 117 were male. Mean follow-up was 8.1 +/- 3.6 years. The deformity was noted before the age of 5 in 90%. Type I symmetrical and localized deformity was seen in 33.2%, type II symmetrical but diffuse depression in 23.7% and type III localized or diffuse asymmetrical deformity in 43.1%. It was considered severe in 68.9%, fair in 16.9% and mild in 14.2%. There were significantly more asymmetrical defects in the older age groups. The operation consisted of subperichondral chondrectomy, transverse sternotomy and division of the intercostal bundles at the outer limit of the chondrectomy and suturing the edge of this broad sheet of muscle and perichondrium to the anterior surface of the chest wall more laterally and under tension, elevating and stabilizing the sternum. Results were satisfactory in 83.6% (excellent 44.1%, good 39.5%). Results were not significantly influenced by age, sex, severity, type, symmetry, the extent of cartilage resection or follow-up. Results were inversely influenced by the occurrence of wound problems. The optimal age for operation is considered to be between 5 and 10 years. Both physical as well as psychological cosmetic factors may serve as an indication for operation. PMID- 1616729 TI - Esophageal diverticula. Physiopathological basis for surgical management. AB - From 1980 to 1990, 31 patients were treated surgically in our department for esophageal diverticula: 12 Zenker's diverticula (ZD); 11 mid-thoracic diverticula (MTD); 8 epiphrenic diverticula (ED). Cricopharyngeal dysfunction was detectable in 8 of 12 ZD patients (66.6%). Cricopharyngeal myotomy with diverticulectomy was performed in all cases. There were no deaths. Relief of dysphagia was obtained in all cases. No recurrences of dysphagia or diverticulum were observed at a mean follow-up of 3 years. A motility disorder was observed in 10 of 11 MTD (90.9%). An extended esophageal myotomy with diverticulectomy was performed in 3 cases, an extended myotomy alone in 3 cases, a diverticulectomy alone in 5 cases; an anti reflux procedure was added in 6 cases. One patient died on the 7th postoperative day. All remaining patients were free of symptoms at a mean follow-up of 3.2 years. A motor dysfunction was detected in all 8 ED patients (100%). No diverticulectomy was performed. Six patients underwent Heller-Dor myotomy and 2 underwent Nissen fundoplication. There were no deaths. Relief of symptoms was obtained in all patients, at a mean follow-up of 3.1 years. Myotomy with diverticulectomy represents the treatment of choice in ZD. As regards MTD and ED, the treatment of the underlying motor disorder is the main therapeutic goal, whereas diverticulectomy is reserved to selected patients. PMID- 1616730 TI - Elderly presentation of tetralogy of Fallot precipitated by an occult bronchial carcinoid tumour. AB - A 68-year-old female with tetralogy of Fallot is presented. She had become progressively symptomatic in the 2-3 months prior to referral and at operation was found to have a previously unsuspected neuroendocrine secreting bronchial carcinoid tumour subsequently removed by lobectomy. PMID- 1616731 TI - Intracaval paraganglioma causing superior vena cava syndrome. AB - We report a 46-year old female patient with progressive symptoms and signs of superior caval syndrome. At surgery, the caval vein with a benign intravascular paraganglioma was removed, and a venous interposition using a spiral vein graft was performed. PMID- 1616732 TI - [The research process in grounded theory: some examples of nursing education and nursing practice research]. AB - The purpose of this paper is to describe the grounded theory method; especially of the research process in studies using the method. The article is based on the examples of authors' studies of nursing education and nursing practice. The grounded theory method is qualitative and inductive, analyzing data from the empirical world, from which categories and concepts are emerged. Analysis is made by coding and memorizing. The emerging categories will be structured, restructured and developed continually during the research process. In the final theory the concepts, the relationships between them and their internal and external differences are defined in the social process. The meaning of a good description of the research process is emphasized, because the evaluation of the research studies using grounded theory method are based on well documented research process. PMID- 1616733 TI - [Current and future work roles of hospital nursing directors]. AB - This study has three aims: 1) to examine the present role of hospital nurse directors; 2) to find out what changes will occur in their role in the near future; and 3) to explore what their future role should be. The data were collected by a means of a mail questionnaire in winter 1990 from 50 nurse directors and 42 chief physicians of departments and 50 head nurses of wards from five Finnish university hospitals and from five other large acute hospitals. The nurse directors assessed their present role as being the most active and the head nurses as the least active in the examined 27 leadership functions. Largest differences were found in the evaluation of the hospital nurse directors' present role between the nurse directors themselves and the head nurses. However, in respect to the future work role the head nurses and nurse directors had rather similar expectations. Both emphasized research and development of the nursing staff and nursing care. The chief physicians thought that nurse directors should concentrate more on the internal leadership functions of the hospitals such as personnel management, solving the conflicts between the staff and performing routine functions of personnel management. The nurse directors themselves emphasized the external functions of hospitals in their present and future work role, such as networking and negotiations outside the hospitals and financial management. The differences in the evaluations of the present role and in the expectations concerning the future role of nurse directors indicate conflicting views between the the three groups. All respondents perceived nurse directors as being important and needed in hospitals. They also considered that non-nurses cannot function as directors of nursing services. PMID- 1616734 TI - [Nurses' viewpoint of the effects of breast cancer of hospitalized patients on their continued participation in self care]. AB - This article is focused on the viewpoint of nurses about the effects of breast cancer to a patient. What kind of opportunities as well as resources do the nurse notice that the patient has and how much does the nursing practice create possibilities for a patient to participate. The questionnaire developed was sent to special nurses, nurses, radiological nurses and specialized radiological nurses in clinics and wards of one university and six local hospitals (N = 125) in southwestern Finland. Seventy-one percent of respondents returned the questionnaire. The analysis of the data was based on percentual distributions, correlations and cross-tabulations. The main statistical analysis was made by using log-linear models. The meaning of breast cancer to a patient was seen to depend on patient's total life situation. The age, personality and values are imagined to effect how the person reacts in an illness situation. According to nurses patients have resources to participate in more active way in their care. The reasons set limits in patient's participation are seen to be unclear purposes in care and different kind of reasons based on health care staff, nursing practice, the organization and also patients. PMID- 1616735 TI - [Critical thinking during the clinical teaching at the beginning of nursing students' clinical education]. AB - This article examines how critical thinking is seen in learning decision making during the clinical lessons in the beginning of nursing students' clinical education. The data has been collected by taping all the clinical lessons (11) of the students (32). The data was analyzed by using content analysis both quantitatively and qualitatively. The phases of the nursing process, in other words the phases of decision making appeared clearly in the discussions. A lot of assessment of the nursing needs of the patient appeared clearly. Physical needs were focused among the nursing problems. The objects of the nursing were defined nurse-centrically and generally. The discussion about the implementation and the evaluation of the nursing received insufficient attention. There were presented neither alternative solutions of the care nor any reasons for proposed solutions. Learning of the students represented mainly superficial, mechanical learning, lacking critical thinking. PMID- 1616736 TI - [The 34th Congress of the Japanese Society of Child Neurology. July 11-13, Omiya, Japan. Abstracts]. PMID- 1616737 TI - [Oropharyngeal functional assessment in patients with Zenker's diverticulum. Manometric and isotopic study]. AB - Twenty patients with the diagnosis of Zenker's diverticulum were studied clinically and manometrically. In 8 patients oropharyngeal clearance of liquid isotopic markers was done. In three, esophageal emptying of a marked meal was also studied. Clinically, sixteen patients had oropharyngeal dysphagia, while for remained asymptomatic. Dysphagia was severe in only five patients. In half of the patients there were signs of hiatus hernia and/or reflux. Pharyngo-sphincteric incoordination was present in 70% of cases with a mean resting pressure of the LES significantly lower than in controls. There were no differences among patients with or without reflux. Isotopic esophageal clearance was not useful as a test, as there were no significant differences with the control group. On the other hand, esophageal emptying of solid isotopic meals may show the persistence of food in the diverticular sac long time after the meal. PMID- 1616738 TI - [Zenker's diverticulum. The clinical manifestations and treatment]. AB - Clinical manifestations and surgical results are analyzed in a retrospective study of 16 patients with a Zenker's diverticulum. Pharyngoesophageal diverticulum are an uncommon anomaly, producing cervical dysphagia and recurrent airway infections. Treatment should be surgical, as earliest as possible. Morbidity is very low and mortality very rare. PMID- 1616739 TI - [The effect of resection of the jejunum and ileum on intestinal mucosal trophism. An experimental study on the rat]. AB - Intestinal resection leads to anatomo-physiological adaptive changes in the small bowel depending on its localization and extension. Two 50% resection models were done, jejunal resection (55 cm.) and ileal resection (55 cm.), in the attempt to determine the trophic response of the remnant bowel from jejunal and ileal samples. Significant increases were seen in mucosal villous length, jejunal values were greater than ileal and the greatest values were when the whole ileum was conserved. No significant changes were observed in DNA contents. These data suggest the importance of the ileal segment in the intestinal adaptive process, especially on the jejunal segment, as well as the apparent end of this response two weeks after resection. PMID- 1616741 TI - [Biliary calculi resistant to dissolution with bile acids: their heterogeneous composition and diversity of treatment response]. AB - We have studied thirteen biliary stones resistant to biliary acids, using technical methods of stereomicroscopy, scanning electronic microscopy and EDX analyses. We have investigated changes on surface. Three biliary stones did not change and were considered resistant. Seven biliary stones appear partially dissolved and we observed many irregularities on surface and/or concentric dips in relation with cholesterol dissolution. In six cases, biliary pigment alternates with cholesterol. In three cases we observed a calcium carbonate coat on surface. One case included organic fibers. One biliary stone showed cholesterol with spherical bodies of calcium carbonate and pigment. It was a relapsed case of combined treatment. Three stones are composed of small black portions of polymerized calcium bilirubinate, rich in copper and iron. Our results demonstrate that biliary stones previously selected for treatment are a heterogeneous group. Because of this fact we get variable and unpredictable results. PMID- 1616740 TI - [The duration of the effect of norfloxacin on the fecal flora in cirrhosis patients]. AB - The aim of the study has been to assess if intermittent treatment with norfloxacin could be able to maintain selective intestinal decontamination in cirrhotic patients in order to prevent bacterial infections. Group I (n = 10, subgroup Ia, n = 5, hospitalized cirrhotics, subgroup Ib, n = 5, outpatient cirrhotics) received 400 mg/24 h norfloxacin 7 days. Group II (n = 5, outpatient cirrhotics) received 400 mg/12 h norfloxacin 7 days. Gram-negative aerobic bacilli of the fecal floral were strongly suppressed in all patients at the end of the treatment, and they totally (Group I) or partially (Group II) recovered the initial concentrations 7 days after the end of the treatment. There were not significant differences between subgroups Ia and Ib. These results suggest that prophylactic treatment with norfloxacin in cirrhotic patients at high risk of infection should be continuous during the period in whom patients must be submitted to selective intestinal decontamination. PMID- 1616743 TI - [Spontaneous bacterial peritonitis]. PMID- 1616742 TI - [Biliary surgery on those over 70: an analysis of 109 cases]. AB - 109 patients older than seventy years of age and operated of gallstone disease in our service during a period of 4.5 years are presented. The average age of the series was 78.8 years, with a male/female (M/F) ratio of 1/1.6. 77% of the patients were admitted on an emergency basis due to a complication derived from the gallstone disease they were suffering. Only 39.8% of the patients were previously diagnosed of gallstone disease at the time of admission and 10% presented an associated surgical condition which was treated simultaneously. Overall morbidity of the series was 36%, with a mortality of 2 cases (1.9%). PMID- 1616744 TI - [The composition and structure of cholesterol biliary calculi]. AB - The order and composition of the various elements that are present in the cholesterol stones has been analyzed and a useful model that should help in the study of already formed stones is proposed and therefore a better understanding of the lithogenesis and the physiopathological conditions in which stones develop. The existing components are described from the core up to the crust, case emphasizing the heterogeneity of the core, the calcium palmitate around it and the cholesterol disposition. The various forms of presentation of calcium carbonate are defined as well as the different types of ooliths. PMID- 1616745 TI - [Severe digestive hemorrhage of an unusual etiology. Visible isolated and bleeding esophageal vessels]. AB - We describe two patients with massive upper gastrointestinal bleeding. The upper gastrointestinal endoscopy revealed jet haemorrhage in the distal portion of the esophagus, from a visible vessel, without esophageal mucosal damage. In both cases arteriography was performed, and did not show vascular malformations or fistulous points. The patients were successfully treated, one with endoscopic sclerosis and balloon tamponade, and the other with endoscopic sclerosis and transcatheter embolization through left gastric artery. For the time being we do not know the true importance of these findings, but we hope that other reports help us to understand the clinical and pathologic features of this vascular lesion, and the best therapeutic approach. PMID- 1616746 TI - [Spontaneous rupture of the spleen in chronic pancreatitis]. AB - The appearing of splenic complications in the evolution of acute or chronic pancreatitis is a known fact, even though it is not that frequent. A case of splenic rupture happens during an acute bout of chronic pancreatitis. The possible pathogenic mechanisms implied are analysed as well as the forms of presentation and the approximation to diagnosis. The great difficulty in the diagnosis is determined by the scarce specificity of the clinical and biochemical manifestations. Therefore, it is called the attention upon the eventuality of this complication and the therapeutic attitudes which should be adopted. PMID- 1616748 TI - A problem with modern dental materials. AB - It may come as a surprise to learn that there is more than one discipline in medicine dealing with artificial organs. The obvious one is bio-engineering, which is largely concerned with fashioning existing biologically acceptable materials into useful spare parts such as hip or knee joints. The materials themselves hardly change, and the difference between rival prostheses lies more in design than novel chemistry. This is the world of titanium or cobalt-chromium joint designs, bone screws and plates, orthotic limbs, supports and wheelchairs, and futuristic ideas such as miniature video cameras for artificial eyes. PMID- 1616747 TI - [Hepatitis associated with taking diclofenac]. PMID- 1616749 TI - 'Orthodontic relapse'. PMID- 1616750 TI - 'Orthodontic relapse'. PMID- 1616751 TI - British orthodontics. PMID- 1616752 TI - Glutaraldehyde disinfectants: uses and management. PMID- 1616753 TI - 'A practical gloving and handwashing regimen for dental practice'. PMID- 1616754 TI - 'A practical gloving and handwashing regimen for dental practice'. PMID- 1616755 TI - The aetiology, epidemiology, pathogenesis and changing pattern of infective endocarditis, with a note on prophylaxis. AB - Infective endocarditis remains a life-threatening condition, although the number of deaths due to this disease has fallen by 80% over the past 50 years. Dental undergraduate and postgraduate teaching rightly emphasises the use of prophylactic antibiotics for those patients most at risk of developing the condition. However, the types of patients at risk have also changed with the increased use of antibiotics and availability of heart surgery. While oral microorganisms may be incriminated in infective endocarditis, causal organisms arise from a number of other sites and in many cases the portal of entry is unknown. It is now thought that the proportion of cases that are apparently dentally related is probably smaller than previously believed. This article concentrates on the mechanisms by which this disease occurs, an area which is often poorly understood by undergraduates and postgraduates alike. An extract is included from the Lancet, which provides the most recent recommendations for endocarditis prophylaxis. PMID- 1616756 TI - The use of the CPITN to monitor the outcome of periodontal treatment in a dental hospital setting. AB - The Community Periodontal Index of Treatment Need (CPITN) is recommended for monitoring the outcome of periodontal treatment, yet to date there is only one published prospective study that has used the index for that purpose. The aim of the present study was to monitor the outcome of periodontal treatment of 42 patients referred to a consultant periodontist in a dental hospital. The CPITN was recorded at baseline by a single trained examiner. Subsequently, the patients were examined independently by the consultant and a treatment plan formulated. The prescribed treatment was carried out, and a record was maintained of the type of treatment provided and the number of visits involved. The CPITN was recorded again approximately 6 months after baseline by the same trained examiner. Full data were obtained for 36 subjects; most (22 patients) had deep pockets (CPITN, code 4) at baseline, while nine had shallow pockets (CPITN, code 3). Patients with deep pockets at baseline required more complex treatment and more visits (mean 6.2 visits) than patients with shallow pockets, calculus or gingival bleeding (mean 3.5 visits). Nineteen of the 22 subjects with deep pockets at baseline showed a reduction in the number of sextants with deep pockets after 6 months; however, in only 11 of these subjects were the number of sextants with deep pockets reduced to zero. In the light of these findings a modified format for summarising such CPITN data is recommended. PMID- 1616757 TI - Dental attendance behaviour of children in Scotland between 1983 and 1988. AB - Parental permission was sought to monitor longitudinally the dental care of a sample of 5, 8, 12 and 15-year-olds in Scotland who took part in the 1983 national survey of children's dental health. The dental treatment records of those who volunteered were released by the Scottish Dental Practice Board and the Information and Statistics Division of the Common Services Agency to the Dental Health Services Research Unit at Dundee University. The baseline epidemiological survey data was passed on by the Office of Population Censuses and Surveys. During the period 1983 to 1988, less than half of the children in the sample attended for dental care at least once a year on average (ie at least five times in five years) and most also let a lapse of more than 2 years occur between dental visits at some time within the 5-year study period. Around 20% of the three youngest age groups changed dentist three or more times. These results indicate that steps need to be taken to improve the dental attendance of children in Scotland if the principle of continuing care underlying the new General Dental Service contract is to be achieved. PMID- 1616758 TI - Wystan Peach Memorial Lecture. The profession and the press--friend or foe? PMID- 1616759 TI - Arranging dental care for hostel dwellers: a pilot project. PMID- 1616760 TI - 'What other journals say'. PMID- 1616761 TI - 'Permanent damage to inferior alveolar and lingual nerves during the removal of impacted mandibular third molars'. PMID- 1616762 TI - Why has no one ever looked at my gums before? PMID- 1616764 TI - 'Do you treat HIV positive patients?'. PMID- 1616763 TI - 'A European view of fluoride supplementation'. PMID- 1616765 TI - Baseline chartings. PMID- 1616766 TI - Carriers of infection within the profession. PMID- 1616767 TI - Prosthetic restoration following localised maxillary resection. PMID- 1616768 TI - Allergic reactions to rubber gloves in dental patients: report of three cases. AB - Three cases of allergy to rubber are described, in which the patients exhibited peri-oral rashes following dental treatment by personnel wearing latex rubber gloves. Two of the patients were aware of possible allergy to domestic rubber products but did not reveal this as part of their medical history. With the increase in numbers of dentists wearing rubber gloves it is probable that there will be many more such cases reported in the future. Rubber products must then be added to the list of potential allergens which may be of some import to the practice of dentistry. PMID- 1616769 TI - Metastatic breast carcinoma presenting with multiple gingival epulides. AB - A case is reported of a young patient with metastases from the breast presenting as rapidly growing gingival epulides. The initial gingival lesion appeared shortly after a bone scan had given no evidence of dissemination of the diagnosed breast cancer. Two further lesions appeared at different sites within 3 weeks. PMID- 1616771 TI - The British Dental Journal: a report on its activities 1986-1991. AB - The contents of 139 issues of the British Dental Journal, published between January 11, 1986 and December 1991, have been analysed. Part I of the Journal contains, on average, one Leader, eleven items of news and notes, 12 letters and eight abstracts/book reviews. One thousand, three hundred and seventeen manuscripts were submitted for publication during the 6-year period. Of these, 403 original articles, 119 case reports and 203 review articles were accepted and published in Part II. Part III of the Journal is devoted to annual and other reports and policy documents, worldwide dentistry, practice management and vocational training, dental electives, trade news, meeting reports and obituaries. Over 40 'strap headings' denoting specialised areas of dentistry were used to describe articles published. Almost one-fifth of the papers were concerned with restorative dentistry. Case reports comprised 14% of the papers published. Oral surgery/oral medicine/oral pathology, and related subjects accounted for nearly 15% of papers published. Articles concerned with community dental health, orthodontics and paediatric dentistry accounted for a similar proportion of the total, as did the section comprising general dental practice, vocational training and practice management. Anaesthesia, analgesia, medical topics, microbiology and therapeutics took up 12% of articles published. The remaining 12% consisted of articles on dental education and research, oral biology, dental history, auxiliaries, dental instruments and diagnostic aids. PMID- 1616770 TI - Accidental impaction of partial dental prostheses in the upper gastrointestinal tract. AB - Three accidental cases of accidental ingestion of radiolucent upper partial dentures are presented. As impaction in the upper gastrointestinal tract has a serious morbidity and even mortality, we recommend that dental surgeons consider this possibility when designing a prosthesis to replace anterior teeth. PMID- 1616772 TI - Putting the BDJ to bed. AB - Twenty-two times a year, usually once every 2 weeks, the British Dental Journal drops through letter-boxes around the world. Some recipients read the Journal cover to cover, others concentrate on specific sections ('Letters to the Editor' are avidly scrutinised), some turn straight to the 'Classified' section and some put it away for 'later on'. Considering the amount of effort put into producing each issue of the BDJ, it would be deflating to think that some recipients skim quickly through it; realistically this must be the case. How many readers, however, stop for a moment to consider how the BDJ came into being? While the actual production of the BDJ is carried out in exactly the same way as any other glossy, colour magazine, whether it be Country Life or Woman's Own, there is a great deal of extra work besides, as it is a scientific journal (see p453). This article looks at who and what are involved in producing an issue, from the perspective of the team in the editorial office. PMID- 1616773 TI - TEAMWORK in the South Seas. AB - The Pacific island nation of Kiribati has adopted the BDJ TEAMWORK initiative as a training programme for government dental assistants. TEAMWORK has proved to be adaptable to a hot climate. PMID- 1616774 TI - Let there be light--the laser in dentistry. AB - A damp and dull London day in March somewhat contradicted the title of the meeting of the Odontology Section of the RSM, Let there be light--the laser in dentistry, but there was no doubt, once inside, that the organisers had, with perfect timing, caught the interest of the profession as a Barnes Room packed to capacity was greeted by the president of the section, Margaret Seward. Rather apologetically, she confessed that the film Goldfinger was unavailable, but promised us equal fascination with a galaxy of international experts to guide us through a maze of new developments in laser dentistry. PMID- 1616775 TI - [The unemployed work in the health sector]. PMID- 1616776 TI - [A school with its own "sick ward"]. PMID- 1616777 TI - [Albanian hospital: shortage of everything]. PMID- 1616778 TI - [Illness absenteeism. We must take this seriously]. PMID- 1616780 TI - [Hedmark: time for students]. PMID- 1616779 TI - [Reform in Health Services for Mentally Retarded: Aksel, address Bjornemyrveien]. PMID- 1616781 TI - [Quality assurance: avoid all waiting]. PMID- 1616783 TI - [Exposure of the Norwegian Nurses' Association: nurses in the media]. PMID- 1616782 TI - [7 out of 10 use NSF's curriculum plan]. PMID- 1616784 TI - [Use of power against disagreeable servants. Interview by Bjorn Arild Ostby]. PMID- 1616785 TI - [How long shall we keep quiet?]. PMID- 1616786 TI - [Motorized ambulance services or private ambulance corporation?]. PMID- 1616787 TI - [Children--fate or right?]. PMID- 1616788 TI - [Loyal to our own kind or faithful to outsiders?. Interview by Marit Fonn]. PMID- 1616789 TI - [Substance abuse]. PMID- 1616790 TI - [Blankholm attacks right to breastfeed]. PMID- 1616791 TI - [Fight for life. Interview by Siv Barstad]. PMID- 1616793 TI - Prospects for reducing virus-associated human cancers by antiviral vaccines. AB - The last 25 years have seen a major effort to identify human viruses that either cause cancer in humans directly or can be considered significant cofactors or promoters of cancer. The prevailing view is that tumor-associated viruses are necessary but not sufficient for tumor causation. A long latent period between the initial infection and the appearance of the neoplasm is the norm. Generally, the virus implicated as causative is integrated into cellular DNA. Various virus types have been identified; these include both DNA- and RNA-containing agents from the hepadnavirus, herpesvirus, papovavirus, oncornavirus, and lentivirus groups. Although these candidate viral agents are less prevalent in the developed world, hundreds of millions of people are infected world-wide, and about 1 million infected people develop virus-associated tumors annually. Furthermore, nonviral cofactors are suspect or have been identified in the genesis of many virus-associated cancers. A major global approach to prevention of the initial infection can be made by developing efficacious and cost-effective vaccines. An approved human vaccine is available in one case, whereas in every other situation indications exist that a candidate vaccine may soon be available. PMID- 1616792 TI - Designer foods: effects on development of cancer. AB - There are numerous anticarcinogens in the diet. An important question is how to use such substances in an effective, directed way to reduce cancer risk in humans. The "designer foods" concept is one approach for accomplishing this goal. Foods would be engineered to contain effective levels of anticarcinogens. This idea will work only to the extent that there is sufficient scientific knowledge on which to base such food design. Obviously, it is not sufficient simply to extrapolate from animal data to humans. A hypothetical example of the possible "designer fat substitute" is presented and discussed. PMID- 1616794 TI - Tumor-susceptibility markers. AB - Genetic analyses of unusual hereditary cancers and of common neoplasms suggest that tumorigenesis proceeds through a series of genetic alterations involving oncogenes and tumor-suppressor genes. Such genes can be viewed as tumor susceptibility genes, and DNA tests that examine them might be useful in determining an increased risk of cancer development before the onset of a tumor. Indeed, DNA tests have already proved useful in the genetic counseling of families with an increased risk of rare inherited diseases such as retinoblastoma, multiple endocrine neoplasia type 2a, or Li-Fraumeni syndrome. The current investigation of these familial disorders is enabling the development of expertise, reagents, and methods that will eventually focus on the most common cancers. In assessing risk for these common tumors, several genes will probably require study to achieve more accurate prediction of cancer risk. For example, genetic abnormalities of the ras oncogene and of either the retinoblastoma gene (Rb) or the p53 tumor-suppressor gene have been found in many tumors and appear to be particularly important in the study of individuals at increased risk of lung, breast, or colon cancers. In addition, the study of tumor-associated markers that might already be detectable in the preneoplastic state can be carried out in parallel with tests that search for evidence of mutations in tumor susceptibility genes. Finally, both classes of markers might be complementary in genetic counseling or screening of populations at increased risk. However, the capacity for detecting tumor-susceptibility markers creates a responsibility for the physician in terms of the proper use of this information. PMID- 1616795 TI - Identification of cancer-prone individuals: p53 and family cancer syndromes. AB - Progress in prevention of any disease is enhanced by the identification of a group of individuals who are at increased risk to develop the disease. The ability to detect families with evident predisposition to malignancy provides a unique opportunity to study high-risk groups. Recent studies of the p53 gene have suggested that heritable mutations in this gene may predispose affected individuals to the development of a wide variety of tumors. In this article, evidence for the involvement of p53 in inheritable cancers is assessed, and the implications for future studies are discussed. PMID- 1616796 TI - Animal cancer tests and cancer prevention. AB - The toxicological significance of exposures to synthetic chemicals is examined in the context of exposures to naturally occurring chemicals. We calculate that 99.99% (by weight) of the pesticides in the US diet are chemicals that plants produce to defend themselves (nature's pesticides). Only 52 of these natural pesticides have been tested in high-dose animal cancer tests, and 27 are rodent carcinogens; these 27 are shown to be present in many common foods. The toxicology of synthetic chemicals is compared to that of natural chemicals, which represent the vast bulk of the chemicals to which humans are exposed. It is argued that animals have a broad array of inducible general defenses to combat the changing array of toxic chemicals in plant food and that these defenses are effective against both natural and synthetic toxins. Synthetic toxins (eg, dioxin) are compared to natural chemicals (eg, indole carbinol [in broccoli] and ethanol). The finding that, in high-dose tests, a high proportion of both natural and synthetic chemicals are carcinogens, mutagens, teratogens, and clastogens (30%-50% for each group) calls into question current efforts to use these tests to protect public health by regulating low doses of synthetic chemicals. The administration of chemicals at the maximum tolerated dose in standard animal cancer tests is postulated to increase cell division (mitogenesis), which in turn increases rates of mutagenesis and, thus, carcinogenesis. The animal data are consistent with this mechanism, because a high proportion--about 50%--of all chemicals tested (whether natural or synthetic) are indeed rodent carcinogens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616797 TI - Leukemia in children and paternal radiation exposure at the Sellafield nuclear site. AB - Childhood cancer around nuclear installations has been studied in recent years, particularly in the United Kingdom but also in other countries. The early studies were prompted by the suggestion of a 10-fold raised level of childhood leukemia around the Sellafield nuclear site in England, which was confirmed and followed by the identification of generally smaller excesses around some (but not all) other nuclear sites in the United Kingdom. Marked excesses have not been reported in other countries. The increased leukemia rate around Sellafield has been further investigated by examining individual cases in detail in epidemiological cohort and case-control studies. The raised incidence seems to have been concentrated in children born in the local area but not among children who moved in after birth and was particularly associated with fathers who had experienced higher levels of occupational external ionizing radiation exposure at Sellafield before their children's conception. The underlying cause of this statistical association is not yet clear, but the findings have important potential implications for radiobiology and for protection of radiation workers and their children. PMID- 1616798 TI - Relationship of hormone use to cancer risk. AB - Exogenous hormones are widely prescribed in the United States, primarily as oral contraceptives and hormone-replacement therapy. Each of these frequently used categories of drugs has important potential for altering risk of several major human cancers. The efficacy of oral contraceptives in preventing ovarian cancer and endometrial cancer is well established. There remains controversy about the relationship between oral-contraceptive use and breast cancer risk, but most studies show that use in the postmenarcheal and perimenopausal periods is associated with an increased risk of breast cancer in a duration-dependent manner. As with oral contraceptives, the relationship between estrogen replacement therapy and breast cancer risk is controversial, but several well designed studies showed a moderate increased risk after long-term use. Estrogen replacement therapy is a major cause of endometrial cancer. Combination hormone replacement therapy will probably reduce some of the excess risk of endometrial cancer, but few epidemiological data exist on this relationship. The sparse data suggest that combination therapy may enhance breast cancer risk. As with endometrial and ovarian cancers, hormonal chemoprevention of breast cancer is also feasible. We review two such strategies, ie, gonadotropin-releasing hormone agonists and the antiestrogenic drug tamoxifen. PMID- 1616799 TI - Health risks associated with excessive warnings about alleged cancer risks. AB - As the adage states, "when everything is dangerous, nothing is." If the word carcinogen (cancer-causing agent) is used to designate a spectrum of products, chemicals, and other environmental exposures, then the classification cancer causing when referring to the results of human epidemiological studies becomes meaningless. Thus, the emerging "carcinogen-of-the-week" phenomenon is counterproductive in preventing the toll of human cancer in that it diverts attention from real causes. PMID- 1616800 TI - Evidence and overview of global tobacco problem. AB - Tobacco use, both smoking and chewing, is a very old habit. Machine-made cigarettes appeared early in this century. As a consequence, lung cancer increased substantially. The evidence relating cancer to smoking and chewing is summarized. Various forms of tobacco use are briefly described. Tobacco exports are an important source of hard currency for some developing countries. In the Western world, seven major international companies control major market shares. In contrast, tobacco monopolies exist in eastern Europe, Japan, and China. The public health interests are represented by the relevant national and international associations and some governments. Smoking is the largest cause of avoidable death in developing countries after infectious disease and malnutrition. PMID- 1616801 TI - Dietary recommendations for cancer prevention: public policy implementation. AB - Dietary recommendations for cancer prevention advise reduced intake of fat; increased intake of fruits, vegetables, and grains; and moderate intake of alcohol and salt-cured, salt-pickled, and smoked foods. These recommendations are virtually identical to those issued by public health agencies for the prevention and treatment of coronary heart disease, diabetes, hypertension, and other chronic diseases, as well as for the health promotion of the general public. The consensus on these recommendations suggests the need for public policies to promote their implementation. These policies should be designed not only to encourage improvements in the dietary knowledge, attitudes, and behavior of individuals but also to address environmental and institutional barriers to dietary change. PMID- 1616802 TI - Defining and targeting an audience for cancer-prevention messages. AB - The target audience for cancer-prevention messages is not the cancer patient. Cancer-prevention messages should be designed for and directed toward groups of people who have been determined to be at risk for the disease. Potential audiences may vary widely in size and nature, depending on the specific cancer, its cause, and its etiology. The prevention of specific disease, eg, lung cancer, typically demands some behavior on the part of the recipient of a cancer prevention message. Thus, members of a target audience may be asked to stop smoking or to refrain from starting. Each potential target audience is likely to be unique and cannot always be reached with typical mass-media campaigns. Messages designed to be effective for such special audiences may be required if a significant impact on behavior is to be obtained. This article attempts to identify potential audiences for cancer-prevention messages and develops the nature of the media to be used, the sources to be employed, and the arguments to be developed in such a campaign. Characteristics (eg, sex, race, age, marital status, and socioeconomic status) are used as examples of variables that may dictate the nature of cancer-prevention campaigns. PMID- 1616803 TI - Communicating cancer-prevention information. AB - The message to the public regarding cancer prevention should emphasize moderation and evolutionary change in living habits rather than revolutions and focus on total life-style not just individual factors. It is essential to keep people focused on the modifiable factors that can really make a difference. Currently, people worry about minutiae, ie, possible substances in the environment that might cause some cancers, rather than the main, more clearly defined factors, eg, smoking, diet, and sedentary living. The media must play a major role in cancer prevention, assisted by rational, clear-speaking professionals. PMID- 1616804 TI - Positive evidence on effectiveness of selected smoking prevention programs in the United States. AB - Various smoking intervention approaches have been demonstrated to successfully alter smoking behavior among individual smokers, but it is difficult to demonstrate the benefit of these individual cessation approaches across the population of smokers. In contrast, efforts that concentrate on altering the social and economic environment within which the smoker smokes, most notably the media, taxation, and changing the social acceptability of smoking, have been linked to substantial shifts in the smoking behavior of the US population. Attacking tobacco use as a form of sociological carcinogenesis, rather than focusing on the individual smoker, allows alteration at the root of smoking behavior, ie, its personal, social, and psychological utility for the smoker. PMID- 1616805 TI - Trends in tobacco use in Europe. AB - Tobacco consumption in Europe can be estimated from several sources, including sales statistics and population surveys. The first source provides a reasonable estimate of total tobacco consumption, whereas the second gives estimates of the prevalence of smokers by sex and age. In 1950, daily cigarette consumption by adults in European countries varied between 1.7 in Portugal and 6.9 in Ireland, the corresponding US consumption being 8.9. In 1989, the variation was much smaller, ie, between 3.5 in the Netherlands and 10.1 in Greece. In the countries where consumption was high in 1950, maximum consumption was achieved around 1975, followed by stabilization or reduction. In other countries, where consumption was low in 1950, it is still increasing. In a 1987 European survey, the proportion of current smokers varied between 33% in Portugal and 46% in Denmark. Much of this difference comes from the low prevalence of smoking habits in the adult female population of southern Europe. PMID- 1616806 TI - US tobacco export to Third World: Third World War. AB - Global tobacco-related mortality will rise from the current 2.5 million to over 10 million annually by 2050. Most of this increase will occur in developing countries, where legislative controls and other measures that succeed in limiting the use of tobacco in industrialized countries do not exist or are at best inadequate. Of particular concern is the penetration of developing countries by the transnational tobacco companies, with aggressive promotional campaigns that include specific targeting of women, few of whom currently smoke in developing countries. The transnational tobacco companies advertise and market in ways long banned in the United States, for example, selling cigarettes without health warnings, advertising on television, and selling cigarettes with higher tar content than the same cigarettes sold in the United States. Also, tobacco advertising revenue prevents the media from reporting on the hazards of tobacco, a particularly serious problem in developing countries, where awareness of the harmfulness of tobacco is low. The transnational tobacco companies interfere with the national public health laws of developing countries via political and commercial pressures to open markets and to promote foreign cigarettes. This has led to an increase in market share by foreign cigarettes, but evidence also points to market expansion, especially among young people. The entry of the transnationals leads to a collapse of national tobacco monopolies or to their changing from unsophisticated government departments that may still cooperate with health initiatives on tobacco to copying the aggressive marketing and promotional behavior of the transnationals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616807 TI - Worldwide expansion of transnational tobacco industry. AB - As smoking rates fall in North America and western Europe, transnational tobacco companies (TTCs) from the United States and Great Britain turn to cigarette markets of the developing world to replace those smokers who have quit or died from smoking. The majority of these markets are dominated by state tobacco monopolies that advertise and promote smoking minimally. Few women or adolescents smoke in those nations. The majority of men do, but they smoke far fewer cigarettes per year than their counterparts in developed nations. Trade barriers in the developing world prevent foreign cigarette companies from entering. TTCs employ various techniques to force open those markets, including trade pressure from the US government. Once the market is open, Western cigarette advertising and promotions target nonsmoking women and children. Retail tobacco outlets increase, smoking rates rise, and more death and disease result. Latin America was the TTC target in the 1960s, the newly developed nations of Asia during the 1980s, and, today, the tobacco giants are pushing into eastern Europe, China, and Africa. If nothing is done, emerging national smoking-control programs will be overwhelmed, and state-owned cigarette monopolies will be taken over by the TTCs. Policies and programs to curb smoking exist, but for various reasons many lesser developed countries have not adopted them. The threat of TTC entry into a closed market offers an opportunity to form national coalitions against smoking, educate the public about the dangers of tobacco use, and implement public health policies and programs to restrict marketing and use of cigarettes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616808 TI - Role of the health professional in ending the tobacco pandemic: clinic, classroom, and community. AB - Physicians and other health professionals have become complacent about the tobacco pandemic, because there is a mistaken belief that the war on smoking has been won. In reality, the survival from lung cancer is little better than it was 30 years ago, and cigarettes have become the most advertised and promoted product in society. The prevalence of overall smoking in the United States has declined by only 0.5%/y during the past decade. Among certain US minority populations, the decline has been far less or nonexistent. Traditional efforts to control the tobacco pandemic have been reactive and static, whereby government agencies, schools, and health professionals provide the public with generic information about the adverse health effects of smoking. As a result of these efforts, it is assumed that individuals will act to change their behavior. In contrast, the tobacco industry is proactive and dynamic, changing its brand-name strategies through advertising and promotion. To more effectively combat tobacco use, health officials need to move beyond patient education and adopt a more active model that includes clinic-based, school-based, and community-based tobacco-control strategies. Use of humorous, satirical images as part of paid counteradvertising campaigns and proactive health education curricula should be part of a concerted effort to end the tobacco pandemic and limit the promotional influence of tobacco companies. PMID- 1616809 TI - Projecting international lung cancer mortality rates: first approximations with tobacco-consumption data. AB - Cigarette smoking is strongly associated with later lung cancer; British data show a 0.83 correlation between tobacco consumption and lung cancer mortality 21 years later. We apply a simple tobacco-consumption model to data from countries in the Organization for Economic Cooperation and Development (OECD) to test the model in some nations and to roughly estimate future rates in others. This analysis provides some indication of the usefulness of the model, which could be applied to predictions for countries in which data are limited. This model predicts a US decline in male lung cancer mortality of approximately 25% by 2005 (a plausible prediction given recent declines in birth-cohort-specific lung cancer mortality rates); it also predicts reasonably well the start of documented declines in lung cancer mortality. According to this admittedly simple model, lung cancer mortality rates will increase in most European countries and Japan until 2000, but the twenty-first-century lung cancer epidemic will mostly occur in Asia. PMID- 1616810 TI - Tobacco litigation--purpose, performance, and prospects. AB - Product liability litigation can dramatize the dangers of tobacco use, stymie industry propaganda efforts, reveal nefarious industry behavior, and force price increases. Recent recognition of nicotine addiction, "discovery" documenting the industry's stonewalling campaign of more than 35 years, and favorable legal developments make future success likely. Litigation can also be used to pressure employers to provide smoke-free working environments, force retailers to obey laws prohibiting sales to minors, require tobacco companies to abandon "colonialist" Third World marketing practices, publicize the falsity of pseudoscientific industry assertions, and prevent television stations from broadcasting tobacco advertising masquerading as sports events. Even defending against harassing legal actions brought by the industry can embarrass the industry and publicly vindicate pro-health groups that oppose it. PMID- 1616811 TI - Advocating on behalf of the facts. PMID- 1616812 TI - International differences in diet and cancer incidence. AB - International variations in the annual incidence rates of reproductive organ and gastrointestinal cancers suggest that they have environmental causes and can be controlled by public health approaches. Secular trends in the national incidence rates of these two groups of tumors and the experiences of migrants moving from countries with low rates to countries with higher rates of these cancers increase the likelihood that public health dietary interventions will lower cancer incidence rates. The results of recent correlation analyses of international variations in the consumption of dietary fat and incidence of large-bowel and hormone-dependent reproductive organ cancers suggest that both the total amount of fat and the specific fatty acids consumed are associated with the incidence of these cancers in national populations and that the associations strengthen with age and are strengthened rather than weakened by the inclusion of potentially confounding and modifying dietary and nondietary factors in the analysis. The consistency of estimates developed with coefficients derived from these analyses and the degree to which they agree with independent observations suggest that they can provide useful parameters for the design of trials to test the hypothesis that they measure causal associations. PMID- 1616813 TI - Life-style and cancer: from epidemiological evidence to public behavior change to mortality reduction of target cancers. AB - Cigarette smoking, alcohol consumption, and diet are of essential importance in modulating risks of cancer of selected sites, as demonstrated by various epidemiological methods. Examples include demographic studies on changing cancer risk, correlation studies on dietary fat and cancers of breast and colon, and case-control studies on highly salted food and gastric cancer. Evidence was also obtained by cohort studies including a census-population-based large-scale prospective study in Japan. Results included elevated risk from cigarette smoking for cancers of most sites; from alcohol consumption for cancers of the upper and lower digestive tract, liver, and prostate; and from daily meat consumption for cancers of the pancreas, colon, lung, and breast. Daily consumption of green yellow vegetables reduced risk for cancer of the stomach, colon, lung, cervix, and prostate. Reports of these results and intensive public education and public guidance by governmental and nongovernmental organizations such as cancer societies, consumer groups, and mass media resulted in a notable change in public behavior in most cases in Japan. PMID- 1616814 TI - Diet modification and gastric cancer prevention. AB - The relative strengths of the etiologic factors identified for gastric cancer are discussed. On the basis of available scientific data, it is recommended that dietary prevention of gastric cancer be based on attempts to reduce the ingestion of foods with a high content of salt and to increase the intake of fresh fruits and vegetables. Other identified etiologic factors offer promise and are being investigated but do not yet justify recommendation to the general public. PMID- 1616815 TI - Cancers associated with high-fat diets. AB - The association between fat intake and several common cancers, eg, those of the colorectum, breast, endometrium, ovary, and prostate, received its strongest support from correlation studies on populations. On an international scale, strong direct correlations were observed between fat intake and incidence or mortality from these neoplasms; several correlations were also observed on a national level and persisted after allowance for major identified covariates. Further support came from the observation of change in rates in migrant groups. This association, however, has been described as being weak in individuals as opposed to populations. Briefly, diets high in fat (and meat) have been associated with high risk of colorectal cancer in several case-control studies, with saturated fat being specifically implicated. However, the strength of the association is generally moderate, and a few disparities have to be considered. In relation to breast cancer, several case-control studies have reported associations with total fat, and there was some indication that the associations might be stronger for saturated fat. These relationships, however, were weak and inconsistent in various studies. Thus, a plausible conclusion from case-control studies is that there is indeed some association between fats and breast cancer risk, which is, however, limited and, hence, extremely difficult to prove in epidemiological terms. To further complicate the issue, the results of cohort studies do not support the association. Data from analytical studies are more limited for endometrial, ovarian, and prostate cancers, but, again, seem to indicate a possible relationship with diets high in fat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616816 TI - Cancer prevention: optimizing life-styles with special reference to nutritional carcinogenesis. AB - Life-style variables, especially those relating to metabolic overload, are significantly linked to risk for human cancer. Although the roles of tobacco use, alcohol abuse, sunlight, and select occupations are well established, the impact of nutrition on human carcinogenesis, and particularly that of excessive intake of fat and low intake of fiber, is less recognized. This article summarizes the essential evidence, recommends optimal fat and fiber intake, and suggests ways in which comprehensive clinical cancer centers can effectively participate in cancer prevention. PMID- 1616817 TI - Keynote address: cancer prevention. AB - Life-style factors that have a major impact on cancer risk are smoking, alcohol consumption, and diet. Current evidence suggests that dietary fat is an etiologic factor for colorectal and postmenopausal breast cancer and that foods high in dietary fiber may be beneficial against colorectal cancer. Clinical prevention trials, augmented by molecular and biological marker studies, will provide new knowledge for diet modification and chemoprevention. These studies are likely to influence the scope of oncology and public health practices of the future. PMID- 1616818 TI - Potential impact of sugar and fat substitutes in American diet. AB - Nonnutritive sweeteners and fat substitutes have achieved rapid consumer acceptance. This is largely due to the perception held by the public that these products are helpful in weight control and diet improvement. The cognitive component in human eating behavior makes it difficult to generalize from animal research. The effectiveness of these products in weight control has yet to be demonstrated conclusively in human research. Currently these products appear to add palatibility to reduced-calorie diets and may be helpful to weight-loss efforts as part of an overall balanced, nutritious diet and healthy life-style that includes exercise. PMID- 1616819 TI - Signal transduction system for growth factor receptors associated with tyrosine kinase activity: epidermal growth factor receptor signalling and its regulation. PMID- 1616820 TI - The role of protein kinase C in insulin action. PMID- 1616821 TI - Importance of substrate conformation in the phosphorylation of chromatin associated proteins by exogenous protein kinase C. AB - Protein kinase C (PKC)-mediated phosphorylation of chromatin-associated proteins was studied in vitro. HL-60 and HeLa nuclear proteins were notably unresponsive to exogenously added brain PKC. In contrast, 3T3 fibroblasts and lymphocytes from primary cultures exhibited PKC-dependent phosphorylation of chromatin-associated proteins when chromatin was induced to expand. Unexpanded nuclei in all cell lines were unresponsive. Responsiveness was particularly obvious in the decondensed chromatin of primary lymphocytes, where a large number of proteins were phosphorylated in response to exogenous PKC. DNAase-I and micrococcal nuclease strongly modulated these phosphorylation patterns indicating that the substrates were DNA-associated. It was concluded that although substrate conformation, i.e. condensation state, was the primary determining factor in control of PKC-dependent nuclear protein phosphorylation, different cell lines greatly differ in their overall responsiveness to exogenous PKC. PMID- 1616822 TI - Functional reconstitution of a receptor-activated signal transduction pathway in Xenopus laevis oocytes using the cloned human C5a receptor. AB - We have used the polymerase chain reaction to isolate and clone the cDNA encoding the human C5a receptor, and have injected the cDNA-derived receptor cRNA into Xenopus laevis oocytes for functional characterization of the receptor protein. Receptor activity was determined either electrophysiologically by measuring the agonist-dependent opening of [Ca2+]i-dependent Cl- channels, or by analysing the agonist-dependent efflux of 45Ca2+ from the oocytes. Using both methodologies, injection of pure C5a receptor cRNA failed to confer C5a sensitivity on the oocytes. In contrast, marked responses to C5a were observed when the receptor cRNA was supplemented with poly(A)+ RNA isolated from undifferentiated HL-60 cells, which is devoid of C5a receptor mRNA. Binding studies using radioiodinated C5a revealed that the C5a receptor polypeptide was in fact synthesized and targeted to the oocyte plasma membrane in oocytes injected with receptor cRNA alone, and that the level of receptor expression was not influenced by coinjection of poly(A)+ RNA from undifferentiated HL-60 cells. These results strongly suggest that the human C5a receptor requires a specific cofactor(s) lacking in Xenopus oocytes but present in undifferentiated HL-60 cells, to generate intracellular signals in oocytes. Identification and characterization of this factor will provide important information about the molecular mechanisms by which G-protein-coupled receptors activate phospholipase C. PMID- 1616823 TI - Inducible overexpression of human protein kinase C alpha in NIH 3T3 fibroblasts results in growth abnormalities. AB - We have stably overexpressed the human protein kinase C alpha (hPKC alpha) in NIH 3T3 fibroblasts under the control of the interferon (IFN) type I inducible murine Mx promoter. These cells showed a 10-fold increase in the transcription of hPKC alpha mRNA after induction with interferon alpha. The increase in the amount and activity of protein kinase C (PKC)-protein in these cells was only about 3-fold after induction with interferon alpha. Compared to control cells which were transfected with the vector only, the NIH 3T3 fibroblasts transfected with the hPKC alpha cDNA showed already a slightly increased PKC-activity and amount of PKC-protein in the absence of interferon alpha. The hPKC alpha overexpressing cells had an altered, "transformed-like" morphology, which was reversed by staurosporine, an increased growth rate and a higher saturation density. The growth rate was further increased by treating the cells with interferon alpha. The hPKC alpha overexpressing cells were able to grow in soft agarose after treatment with phorbol ester such as TPA (12-O-tetradecanoylphorbol 13-acetate). After phorbol ester and interferon treatment a stronger expression of the protooncogene c-jun was detectable in the hPKC alpha overexpressing cells, whereas expression of c-fos and c-myc was not affected. Since these cells show a specific response pattern due to induced PKC alpha expression they might be useful as an assay system for the development of PKC isozyme-specific inhibitors and activators. PMID- 1616824 TI - Heterogeneity of protein kinase C in cultured rat mesangial cells. AB - Two forms of protein kinase C (PKC) activity in cytosol of cultured rat mesangial cells have been characterized in vitro by using histone H1 or endogenous proteins as substrates. Histones H1-phosphorylation was significantly increased only when calcium, phosphatidylserine (PS) and 1,2-diacylglycerol (DAG) or phorbol myristate acetate (PMA) were present together in the incubation medium. EGTA, a calcium chelator, completely inhibited this activity. Upon hydroxyapatite chromatography (HPLC), the PKC activity was eluted as a main peak at 150 mM potassium phosphate with a shoulder at 180 mM. Both peaks corresponded to the type III PKC from rat brain and were identified as PKC alpha isoform by immunoblot analysis. In contrast with what was observed using histone H1, the increased phosphorylation of endogenous proteins in the presence of a mixture of Ca2+/PS, plus either DAG or PMA, was only partly reduced by EGTA. Moreover, the level of the PKC activity detected in the presence of EGTA was comparable to the level of kinase activity, measured in the presence of PS alone or associated with DAG or PMA. This suggests that mesangial cells contain PKC activity which does not absolutely require calcium. Polyacrylamide gel electrophoresis revealed that patterns of phosphorylated mesangial cell proteins are different depending on whether calcium was added or not. In the presence of calcium, PKC strongly phosphorylated the proteins of 53,000 molecular weight, a doublet of 37,000 39,000, the 24,000 and the triplet of 17,000-20,000-22,000 molecular weight. The addition of EGTA to the assays suppressed completely the labelling of most proteins; only the 20,000 molecular weight protein remained strongly labelled, while the 39,000 molecular weight band was only faintly visible. The same patterns of phosphorylations were obtained after omission of calcium in the assays containing only PS and DAG (or PMA). So, the main substrates of calcium dependent PKC are proteins of 53,000, 39,000, 37,000, 22,000, 24,000 and 17,000 molecular weight while the protein of 20,000 molecular weight appears to be the main substrate of calcium-independent PKC. The existence in mesangial cells of at least two forms of PKC, which phosphorylate specific endogenous proteins, emphasizes the complexity of the phospholipid-dependent regulatory cascade and raises the possibility that actions of different regulators may be transduced through distinct PKC isozymes. PMID- 1616826 TI - The influence of aging on the stereoselective pharmacokinetics of propranolol in the rat. AB - The influence of aging on the pharmacokinetics and the tissue distribution of (R) and of (S)-propranolol was studied in 3-, 12-, and 24-month-old rats. After both iv and oral administration of rac-propranolol, the plasma concentrations were higher for the (R)- than for the (S)-enantiomer. For the tissue concentrations, the reverse was true. The free fraction of (S)-propranolol in plasma was about 4 times larger than that of (R)-propranolol, and this is the main factor responsible for the differences in kinetics between the two enantiomers. There was a suggestion for a difference in tissue binding between the two enantiomers. With aging, the plasma and tissue concentrations of both enantiomers increase, probably due to a decrease in blood clearance. Tissue binding did not change much with aging. Notwithstanding the marked differences between the kinetics of the propranolol enantiomers, the changes which occur with aging affect both enantiomers to the same degree. PMID- 1616825 TI - Unusual amino acids. I: Asymmetric synthesis of furylalanine derivatives. AB - Nonproteinogenic amino acids are valuable active compounds from their pharmacological and biochemical effects and also as novel building blocks for peptides. The preparation of furylalanine derivatives by asymmetric hydrogenation is described. Amino-phosphine-phosphinite-rhodium complexes catalyzed the hydrogenation of the prochiral dehydroamino acid precursors in high rate and with enantioselectivities of 70-90% ee. Substrate-catalyst ratios up to 2,000 can be used depending on the catalyst applied. The procedure turns out to be suitable for larger scale preparations. PMID- 1616827 TI - Stereoselective biliary elimination of disopyramide and mono-N desisopropyldisopyramide in humans. AB - The results of a previous pharmacokinetic study of disopyramide (DP) enantiomers in humans suggested that DP and/or mono-N-desisopropyldisopyramide (MND) may show stereoselective extrarenal elimination. Thus, the present study investigates the biliary elimination of DP and MND enantiomers in three patients who had undergone cholecystectomy for cholelithiasis. DP and MND enantiomers displayed biliary elimination. In both subjects, this elimination pathway showed the same characteristics: (1) biliary elimination of DP and MND was stereoselective, (2) the stereoselectivity was opposite to that observed for the metabolic and renal elimination pathways, i.e., the elimination of the (-)-(R)-enantiomer was higher than that of the (+)-(S)-enantiomer, and (3) biliary elimination of MND was higher than that of DP, for both enantiomers. Estimates of the relative contribution of the biliary clearance in the total clearance of DP and MND indicated that this elimination pathway was secondary, especially for DP. The biliary clearance (expressed as % of total clearance) was 1.9 to 4.0% for (-)-(R) DP, 1.2 to 1.7% for (+)-(S)-DP, 7.8 to 22.9% for (-)-(R)-MND, and 5.2 to 10.5% for (+)-(S)-MND. PMID- 1616828 TI - The disposition of venlafaxine enantiomers in dogs, rats, and humans receiving venlafaxine. AB - A stereospecific high-performance liquid chromatographic (HPLC) method was developed for the quantitation of the enantiomers of venlafaxine, an antidepressant, in dog, rat, and human plasma. The procedure involves derivatization of venlafaxine with the chiral reagent, (+)-S-naproxen chloride, and a postderivatization procedure. The method was linear in the range of 50 to 5,000 ng of each enantiomer per ml of plasma. No interference by endogenous substances or known metabolites of venlafaxine occurred. Studies to characterize the disposition of the enantiomers of venlafaxine were conducted in dog, rat, and human, following oral administration of venlafaxine. The Cmax, area under the curve (AUC) and (S)/(R) concentration ratios of the (R)- and (S)-enantiomers were compared. In rats, the mean plasma ratio of (S)-venlafaxine to that of (R) venlafaxine over 0.5 to 6.0 h varied from 2.97 to 8.50 with a mean value of 5.51 +/- 2.45. The Cmax, AUC0-infinity, and t 1/2 values of the (R)- and (S) enantiomers in dogs were not significantly different from one another (P greater than 0.1). The mean ratios [(S)/(R)] of enantiomers of venlafaxine in human over a 2 to 6 h interval ranged from 1.33 to 1.35 with an overall ratio of 1.34 +/- 0.26 (n = 12). These ratios of the enantiomers [(S)/(R)] were not statistically different from unity (P greater than 0.1) indicating that the disposition of venlafaxine enantiomers in humans is not stereoselective and is more similar to that in dogs than that in rats. PMID- 1616829 TI - Five-year study of medical or surgical treatment in children with severe reflux: radiological renal findings. The International Reflux Study in Children. AB - The renal findings on intravenous urography (IVU) are reported in 306 children (73 boys, 233 girls) from eight European centres entered into an international study comparing medical and surgical management of children with urinary tract infection and severe vesico-ureteric reflux followed for 5 years. One hundred and fifty-five children were randomly allocated to medical and 151 to surgical treatment. Protocol and investigative techniques were standardised and randomisation, data collection and analysis were performed centrally in Essen, Germany. At entry 149 (49%) has established renal scarring (79 medical, 70 surgical). Children with normal kidneys (105), areas of thinned parenchyma (52) and grade of reflux were also evenly distributed. IVU was repeated at 6, 18 and 54 months and serial urine culture, 99mtechnetium-dimercaptosuccinic acid scans and plasma creatinine estimations were performed. Two hundred and seventy-two children (89%) completed this follow-up. In 174 children (57%), (90 medical, 84 surgical) there was renal growth without morphological change. New renal scars developed in 19 children treated medically and 20 surgically; 12 (5 medical, 7 surgical) developed in previously normal kidneys. Six followed post-operative obstruction. No significant difference in outcome was found between medical or surgical management in terms of the development of new renal lesions or the progression of established renal scars. PMID- 1616830 TI - Renal function and kidney size in glycogen storage disease type I. AB - Renal failure has been reported recently as a late complication of glycogen storage disease type I (GSD I). We studied the renal function of 23 patients, mean age 10.9 years (range 2.2-21.6 years). The mean glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were 188 +/- 50 and 927 +/- 292 ml/min per 1.73 m2, respectively (normal values for adult controls 90-145 and 327 697, respectively). Hyperfiltration (GFR greater than 145 ml/min per 1.73 m2) was found in 19 of 23 patients. There was no difference in GFR and ERPF between age groups 2-10 and 11-22 years. After a mean follow-up of 2.5 years (range 1-7.5 years) GFR and ERPF did not significantly change. At follow-up 3 patients (all older than 15 years) developed persistent glomerular proteinuria (0.1, 0.5 and 0.9 g/day). Besides a slight increase in fractional excretion of beta 2 microglobulin (FE-beta 2m) in 6 patients, proximal tubular function tests (FE beta 2m, tubular reabsorption of phosphate and glucosuria) were normal. In patients with increased kidney length related to body height, GFR and ERPF were significantly higher than in patients with normal kidney length. We conclude that GSD I is characterised by hyperfiltration and hyperperfusion. The relative increment in kidney length is related to the degree of hyperfiltration. PMID- 1616831 TI - Mesangiocapillary glomerulonephritis associated with meningococcal meningitis, C3 nephritic factor and persistently low complement C3 and C5. AB - We report two unusual cases in which mesangiocapillary glomerulonephritis occurred in association with meningococcal infection. C3 nephritic factor, an autoantibody to alternate pathway C3 convertase, was present. Low serum complement C3 and C5 levels were also noted. The depressed complement levels, in conjunction with terminal complement complexes at the upper limit of normal, suggest activation of the early and late complement cascade. We suggest that children presenting with meningococcal infection should have a regular urine examination, as well as full complement measurements performed, in view of the association with hypocomplementaemic mesangiocapillary glomerulonephritis. Similarly, prophylactic penicillin should be prescribed for patients with mesangiocapillary glomerulonephritis and persistently low C5 levels to prevent meningococcal complications. PMID- 1616832 TI - Good outcome in anti-glomerular basement membrane nephritis. AB - We report a 6-year-old boy with anti-glomerular basement membrane nephritis (Goodpasture's syndrome). Intensive treatment with plasmapheresis and immunosuppression resulted in clearance of antibody and good recovery of renal function. PMID- 1616833 TI - Long-term, low-dose prednisolone therapy in frequently relapsing nephrotic syndrome. AB - The efficacy of daily administration of a small dose of prednisolone was examined in 21 patients with corticosteroid-responsive, frequently relapsing nephrotic syndrome (FRNS). After induction of remission of a third or subsequent relapse with a 6-week course of prednisolone (standard therapy with prednisolone, STP), this drug was continued in a single daily dose of 0.25 mg/kg body weight (low dose prednisolone, LDP) for 18 months. Relapses occurring during this period were treated with STP, following which LDP therapy was resumed. The historical controls comprised 14 patients with FRNS in whom relapses were treated with STP and who were observed over a minimum period of 30 months. The two groups were comparable for age at the onset of nephrotic syndrome and sex. Twenty patients completed LDP therapy, during which 12 had no relapse, 6 had infrequent and 2 frequent relapses (1 patient became steroid dependent and was taken off LDP). Twelve patients were followed for 12-42 months after stoppage of LDP; during this period 7 had no relapse, 4 had infrequent relapses and 1 showed steroid dependence. The number of relapses during LDP therapy (0.5/patient per year) was significantly less (P less than 0.001) than in the preceding 12 months (3.62/patient per year), and continued to remain low during the following 12 months (0.6/patient per year). Whereas the frequency of relapses in the LDP group was similar to that in the historical control group in the 1st year of comparison, it was significantly less during LDP therapy (0.5/patient per year versus 2.25/patient per year). No side effects were observed in patients on the LDP regimen, at the end of which the height percentiles improved in 6 patients and remained unchanged in 14. Our observations indicate that long-term therapy with a small daily dose of prednisolone can significantly reduce the number of relapses in patients with FRNS, and that the beneficial effect may continue even after its stoppage. PMID- 1616834 TI - Reference values for renal concentrating capacity in children by the desmopressin test. AB - Reference values are reported for maximal renal concentrating capacity in children using intranasally administered desmopressin. The report is based on 591 tests in 473 healthy children aged 0.5-13 years. The concentrating capacity increased markedly during the first years of life and reached a plateau at the age of 3 years. The mean value minus two standard deviations was 525 mosmol/kg at 1 year of age and 825 mosmol/kg at 3 years of age. PMID- 1616835 TI - Favorable experience with pre-emptive renal transplantation in children. AB - We retrospectively examined our experience with live-related donor kidney transplants in 66 children during the 7-year period 1984-1990. We compared the clinical courses of 26 children who did not receive any dialytic therapy prior to transplantation with 40 children who were dialyzed (27 via peritoneal dialysis and 13 via hemodialysis). We did not find any statistically significant differences in patient or graft survival between these three groups with a follow up period of 6-87 months. Based on our results, we conclude that pre-emptive transplantation is an acceptable treatment for children who will inevitably require renal replacement therapy. PMID- 1616836 TI - The effect of growth hormone on the growth failure of chronic renal failure. AB - To investigate the effects of growth hormone (GH) on the reversal of growth failure in uremia, recombinant human GH (rhGH) was administered to rats with chronic renal failure (CRF). The dosage of rhGH was 3 IU/day (i.p.) for 13 days after the induction of CRF by 5/6 nephrectomy. Animals were classified into four groups: untreated nephrectomized rats (NX, n = 40), GH-treated nephrectomized rats (NX+GH, n = 18), sham-operated rats fed ad libitum (SHAMAL, n = 27), and sham-operated rats pair-fed with 10 NX rats (SHAMPF, n = 10). NX and NX+GH rats developed a similar and moderate degree of CRF, serum urea nitrogen being (mean +/- SEM) 49 +/- 3 and 54 +/- 4 mg/dl, respectively, compared with 16 +/- 4 and 19 +/- 0 mg/dl in SHAMAL and SHAMPF groups. Weight (56.0 +/- 3.3 g) and length (3.5 +/- 0.1 cm) gains of NX rats were lower than those of SHAMAL rats (94.2 +/- 4.0 g, P less than or equal to 0.0001 and 4.1 +/- 0.2 cm, P less than or equal to 0.01). Growth of the SHAMPF group and the matched NX rats was not significantly different. Weight (56.2 +/- 5.0 g) and length (3.4 +/- 0.2 cm) gains of NX+GH and NX rats were similar, the beneficial effect of GH therapy on growth being observed in only those animals with more severe degrees of uremia. This growth promoting action resulted from greater food efficiency and not from stimulated food intake. The hypercholesterolemia seen in NX rats, 81 +/- 2 mg/dl versus 55 +/- 3 mg/dl in SHAMAL (P less than or equal to 0.0001), was not increased in the NX+GH group, 87 +/- 3 mg/dl. There was a positive and significant correlation between serum cholesterol and serum urea nitrogen values in NX and NX+GH animals. This study suggests that growth impairment of mild CRF is mainly due to malnutrition and is refractory to GH administration. GH therapy improves the growth rate of animals with advanced CRF without aggravating their lipid abnormalities. PMID- 1616837 TI - Transient neonatal distal renal tubular acidosis with secondary hyperparathyroidism. AB - We describe a neonate with distal renal tubular acidosis with secondary hyperparathyroidism manifesting as hyperchloraemia, hypercalcaemia, elevated serum parathyroid hormone (PTH) and life-threatening metabolic acidosis. He exhibited general weakness, tachypnoea, dry skin and weight loss. Urinary excretion of titratable acid and ammonium was decreased. Daily alkali (2.5 mEq/kg body weight) was required to maintain a normal plasma bicarbonate (HCO3-). With alkali therapy, the fractional excretion of HCO3- was below 5%. Serum calcium and PTH were restored to normal promptly on initiation of alkali therapy. After 5 months of alkali therapy, normal growth and urine acidifying ability were restored and alkali therapy was discontinued. The acidification defect in this patient was transient. We consider this patient to be consistent with Lightwood's syndrome of "transient infantile renal tubular acidosis". PMID- 1616838 TI - Hemolytic uremic syndrome due to Escherichia coli O157: H7 in a child with multiple infections. AB - Hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and uremia; it is a common cause of acute renal failure in children. Although many microbial agents have been associated with HUS, only Escherichia coli O157: H7 has been clearly demonstrated to be a major cause of this illness. A case is presented of a healthy 4-year-old boy who had a recent varicella infection; when evaluated for HUS his blood and stool cultures both grew Salmonella montevideo and blood cultures grew group A beta-hemolytic streptococci. A stool cultured on MacConkey-sorbitol agar also grew E. coli O157: H7. An eightfold rise in serum antibodies to E. coli O157: H7 lipopolysaccharide was also demonstrated. The child recovered completely and was healthy 3 years later. Although this child had several infectious agents anecdotally associated with HUS, appropriate culture of stool showed that he also had E. coli O157: H7 infection. Previous cases thought to be due to other pathogens may similarly have been caused by co-infection with E. coli O157: H7. PMID- 1616839 TI - Renal abscess in healthy children: report of three cases. AB - We report three cases of renal abscess in otherwise healthy boys. One had a history of blunt trauma and two of antecedent skin infection. All presented with flank pain and fever. Urine and blood cultures were sterile. The diagnosis was made using ultrasound and computerized axial tomography. The first patient had recurrent renal abscess, following surgery and a short course of antibiotics. Eventually all responded well to long-term antibiotics only. PMID- 1616840 TI - The use of a eutectic mixture of local anesthetic in pediatric renal biopsy. AB - Eight children undergoing percutaneous renal biopsy had eutectic mixture of local anesthetic (EMLA) cream substituted for dermal infiltration of local anesthetic. Five children reported no sensation of the initial skin puncture and only one child reported feeling a sharp object. EMLA cream may form a useful part of pediatric renal biopsy. PMID- 1616841 TI - Cyclosporine in the treatment of azathioprine-induced red cell aplasia following renal transplantation. AB - Azathioprine, a well-known immunosuppressive agent, is used extensively in renal transplantation. There have been several case reports of pure red cell aplasia induced by this drug following a successful kidney transplant. Previous management of azathioprine-induced red cell aplasia included reduction of azathioprine dose, or treatment with cyclophosphamide. We propose the substitution of cyclosporine for azathioprine, in this clinical setting. Not only does cyclosporine allow recovery of bone marrow function, but it maintains a level of immunosuppression which stabilizes renal function in the post-transplant patient. PMID- 1616842 TI - Hyponatremia: pathophysiology and treatment, a pediatric perspective. AB - Hyponatremia is the most commonly observed electrolyte abnormality in hospitalized children. The most serious consequences of hyponatremia and its treatment involve the central nervous system (CNS). Important factors determining the development of clinical symptomatology include: the rate of fall in serum sodium, and the severity and duration of hyponatremia. Acute hyponatremia is associated with increased brain water resulting in varying grades of encephalopathy whereas the osmoregulatory mechanism allows normalization of CNS water content in chronic hyponatremia. It is recommended that the therapy for hyponatremia be initiated on the basis of the presence or absence of symptoms. An increase of 4-6 mmol/l in serum sodium over 10-15 min is recommended in symptomatic patients. Rapid correction of chronic hyponatremia may result in osmotic dehydration syndrome and therefore should be avoided. PMID- 1616843 TI - Lead intoxication--new insights into an old problem. AB - The epidemiology, clinical symptomatology, diagnosis and management of acute and chronic lead intoxication are reviewed. While acute lead intoxication has become rare, the elevated environmental lead burden is thought to play a causal role in hypertension. Lead may also be linked with neuropsychological disorders of children and possibly even chronic renal failure. The epidemiological and experimental evidence for this hypothesis is critically discussed. PMID- 1616845 TI - Molecular aspects of water transport. AB - Due to its fundamental importance, the movement of water across cell membranes has been an active area of research for more than 100 years. This subject is central to consideration of normal water metabolism by terrestrial animals, as well as derangements in overall water balance that are frequently encountered by nephrologists in the care of their patients. The objective of this review is to discuss the most basic aspects of cell membrane water permeability and provide a framework for these data in the context of the care of pediatric patients with renal disease. While the water permeability of most cell membranes can be accounted for by the diffusion of water across the lipid bilayer, other cells, including the red blood cell and certain epithelial cells that line the proximal and collecting tubules of the kidney and the urinary bladder of amphibians, possess specialized water channels. Water channels are composed of specialized proteins that create aqueous pores across cell membrane. Currently, there are active research efforts to isolate and characterize water channel proteins from these cell types. Data concerning the distribution, permeability and function of these various water channels will greatly enhance our knowledge of how water is transported across cell membranes. PMID- 1616844 TI - Tubular and interstitial factors in the progression of glomerulonephritis. AB - All recent studies of the outcome of different forms of progressive glomerulonephritis concur that a major factor, apparently determining outcome, is the presence and severity of tubulointerstitial changes, and not the degree of glomerular alteration. Moreover, at the time of biopsy, tubulointerstitial changes correlate much better with the glomerular filtration rate. These at first surprising findings are not only useful clinically, but should make us think about our models of how progression takes place in so-called glomerular nephritides. In fact, a major tubulointerstitial infiltrate of immune-competent cells is present in all forms of progressive glomerulonephritis, and again correlates with outcome. In addition, it is now clear the tubular epithelium is capable of synthesising and secreting a number of factors important in fibrogenesis, and of displaying major histocompatibility complex class II antigens and leucocyte-adhesion molecules. Tubular cells could thus present peptides to T helper cells and amplify, or maybe even initiate, immune reactions. Finally, fibrogenesis within the kidney is at last being studied, long after studies have been performed on liver and lung. In the past, too much attention has been paid to reversible inflammation and not enough to irreversible cirrhosis of the kidney. PMID- 1616846 TI - Pediatric renal biopsy in the ambulatory care environment. AB - The use of pediatric ambulatory care facilities to perform invasive procedures that have low morbidity is increasingly popular. Over a 2-year period, 46 pediatric renal biopsies were performed in an ambulatory care setting at the Winnipeg Children's Hospital, with the patient discharged the same day. There was no serious complications and adequate tissue was obtained in 45 cases. Renal biopsy may be safely performed on an outpatient basis on carefully selected patients by experienced operators in properly equipped facilities. PMID- 1616847 TI - Normal ranges for urinary excretion of calcium and magnesium in Portuguese children. PMID- 1616848 TI - Clinical quiz. Nail-patella syndrome (NPS) (hereditary osteo-onychodysplasia). PMID- 1616849 TI - Cisplatin and its analogues in the treatment of advanced breast cancer: a review. PMID- 1616850 TI - Promotion of hepatic metastases by liver resection in the rat. AB - In the early period following radical hepatectomy for hepatoma, recurrences in the remaining liver are frequently found. In regenerating liver, implantation and growth of tumour cells released into the portal system during surgical treatment might be promoted. We examined the relationship between liver regeneration and the formation of metastases following hepatic resection. Intraportal injections of rat ascites containing hepatoma AH130 cells at a concentration of 1 x 10(5) cells 0.2 ml-1 were made at various periods following two thirds liver resection in rats. Tumour cell injections immediately at 24 h after surgery resulted in an increased number of hepatic metastases compared with control animals. Tumour cell injections 2 weeks after hepatectomy, however, had no significant difference in effect compared with control rats. In contrast, tumour cells injected immediately after removal of half of the caudate lobe resulted in the same number of metastases as control animals. These results demonstrate that the number of artificially induced hepatic metastases was increased during an initial period of active liver regeneration and was proportional to the volume of hepatectomy. The effect of 5-fluorouracil (5FU) or mitomycin C (MMC) as inhibitors of hepatic regeneration on liver metastasis after hepatectomy was studied. The administration of 5FU (20 mg kg-1) or MMC (0.2 mg kg-1) immediately, 24 and 48 h after hepatectomy resulted in a marked reduction in metastatic lesions. The administration of 5FU caused delays in weight gain and decreases in the wet weight of remaining liver, while MMC had no effect on either. Accordingly, results of 5FU administration may be due to inhibitory effects on liver regeneration whilst that of MMC administration may be due to cytocidal antitumour effect. The effect of OK-432 as an immunoactivator on the implantation and growth of tumour cells in regenerating liver was also studied. Pretreatment with OK-432, 0.5 mg intraperitoneally on 7 consecutive days, had no effect on hepatic metastases. The pathophysiology of liver regeneration may enhance hematogenous hepatic metastasis and release of tumour cells during surgical manipulation may represent an important cause of recurrence following hepatic resection. PMID- 1616851 TI - A DNA repair defect in a radiation-sensitive clone of a human bladder carcinoma cell line. AB - DNA repair was measured in an ionising radiation-sensitive mutant of a human bladder carcinoma cell line. No difference in the rate or extent of double-strand break rejoining was found using the techniques of neutral filter elution and pulsed-field gel electrophoresis. In contrast, significant differences in repair fidelity, measured by plasmid reconstitution, were found. The parent line had a repair fidelity of 84.7% compared with 58.9% for S40b (P = 0.0003). It is suggested that repair fidelity can be an important determinant of radiosensitivity in human tumour cells. PMID- 1616852 TI - Biological activities of phthalocyanines. XIV. Effect of hydrophobic phthalimidomethyl groups on the in vivo phototoxicity and mechanism of photodynamic action of sulphonated aluminium phthalocyanines. AB - Aluminium phthalocyanines substituted to different degrees with hydrophilic sulphonic acid and hydrophobic phthalimidomethyl groups were investigated in vivo as new agents for the photodynamic therapy of malignant tumours. Parameters studied included the photodynamic action on EMT-6 mammary tumours in BALB/c mice, the therapeutic window and the potential for direct cell killing, assayed via an in vivo/in vitro test. Although the efficiency of photoinactivation of the EMT-6 tumour increases by a factor of ten with reduction of the number of sulphonic acid groups from four to two, no further effect was seen with the addition of the hydrophobic phthalimidomethyl groups. Addition of the latter groups however increased the potential for direct cell killing by a factor of two and expanded the therapeutic window by a factor of four, thus improving the usefulness of the dye as a photosensitiser for the photodynamic therapy of cancer. PMID- 1616853 TI - Fluorescence distribution and photodynamic effect of ALA-induced PP IX in the DMH rat colonic tumour model. AB - Aminolaevulinic acid (ALA) is the first committed step in haem synthesis. In the presence of excess ALA the natural regulatory feedback system is disrupted allowing accumulation of protoporphyrin IX (PP IX) the last intermediate product before haem, and an effective sensitiser. This method of endogenous photosensitisation of cells has been exploited for photodynamic therapy (PDT). We have studied the fluorescence distribution and biological effect of induced PP IX in normal and tumour tissue in the rat colon. Fluorescence in normal colonic tissue was at a peak of 4 h with a rapid fall off by 6 h. The fluorescence had returned to background levels by 24 h. All normal tissue layers followed the same fluorescence profile but the mucosa showed fluorescent levels six times higher than the submucosa, with muscle barely above background values. At 6 h the ratio of fluorescence levels between normal mucosa and viable tumour was approximately 1:6. At this time laser treatment showed necrosis of normal mucosa and tumour with sparing of normal muscle. There was good correlation between the fluorescence distribution and the biological effect of ALA-induced photosensitisation on exposure to red light. ALA may be superior to conventional sensitisers for tumours that produce haem as the PP IX is synthesised in malignant cells while the other sensitisers mainly localise to the vascular stroma of tumours. There is also a greater concentration difference between the PP IX levels in tumours and in normal mucosa and normal muscle than with the other photosensitisers raising the possibility of more selective necrosis in tumours. PMID- 1616854 TI - Factors influencing variability of localisation of antibodies to carcinoembryonic antigen (CEA) in patients with colorectal carcinoma--implications for radioimmunotherapy. AB - Tumour localisation of anti-tumour antibodies varies greatly between patients. Factors which may be responsible for this have been investigated in 56 patients with colorectal carcinoma with a view to improving radioimmunotherapy. Thirty seven to seventy-four MBq of 125-I labelled mouse monoclonal antibody to CEA, was given intravenously and tumour resected 70-480 h later. Percentage injected activity kg-1 (% inj.act kg-1) in tumour, was inversely correlated with the time interval between injection and operation (P = 0.004). To assess the influence of other parameters on localisation, patients were divided into two time groups according to time interval between injection and operation, 70-120 h (n = 33) and 144-480 h (n = 23). In neither group was there a significant correlation of % inj.act kg-1 with time. The % inj.act kg-1 in tumour showed a significant correlation with that in the blood for both groups (P = 0.005 and P = 0.01). There was no significant correlation for either time group between % inj.act kg-1 in tumour and serum CEA values, the per cent of tumour cells positive for CEA and vascularity. Tumour to blood ratios varied considerably (range 0.3-28.5:1) suggesting that factors other than time and persistence of activity in the blood contribute to efficient targeting. Tumour to blood ratios were inversely correlated with % inj.act kg-1 in blood for the 70-120 h group (P = 0.007), and were positively correlated with % inj.act kg-1 in tumour (P = 0.012). Autoradiography showed that antibody localised predominantly on tumour cells but was distributed heterogeneously, was not solely related to the expression of antigen and in some cases accumulated in necrotic more than viable areas of tumour. Penetration of antibody into malignant acinar structures was poor and CEA positive cells closer to the blood supply were targeted to a greater extent than distant cells. Preoperative administration of radiolabelled antibody to CEA may be helpful in selecting patients with favourable localisation for radioimmunotherapy. PMID- 1616855 TI - Monoclonal antibody targeting of methotrexate (MTX) against MTX-resistant tumour cell lines. AB - Several Methotrexate (MTX)-resistant sublines of the osteogenic sarcoma cell line 791T were derived by continuous selection in the presence of MTX and 12-O tetradecanoylphorbol-13-acetate (TPA). Studies including assays of the uptake and binding of [3H]MTX and fluoresceinated-MTX, determined that these sublines showed diminished MTX transport, and that none of them appeared to overproduce the MTX target enzyme dihydrofolate reductase. Conjugates of the anti-791T monoclonal antibody 791T/36 linked to MTX via human serum albumin (HSA) were prepared by Dr M.C. Garnett. These were cytotoxic selectively for cells bearing the 791T/36 defined antigen (gp72), and were found to be as cytotoxic to most of the MTX resistant 791T sublines as they were to parental 791T cells. Furthermore, an anti MTX/anti-gp72 bispecific antibody 516 augmented the cytotoxicity of HSA-MTX conjugate to the MTX-resistant 791T variant R120 apparently as efficiently as for parental 791T cells. It is suggested that acquired drug resistance caused by deficient transport mechanisms may be partially or wholly overcome by targeting the drug to a readily-internalised cell surface antigen. PMID- 1616856 TI - Influence of reducing luxury calories in the treatment of experimental mammary carcinoma. AB - The aim of this study was to investigate the influence of dietary calorie intake at three different fat levels on (a) the growth of established methylnitrosourea (MNU)-induced mammary carcinoma, (b) the reappearance of mammary carcinomas after surgical removal, and (c) the growth of manifest lesions in animals treated with the cytostatic agent hexadecylphosphocholine (HPC). A reduction of calories by 30% significantly inhibited tumour growth of manifest mammary carcinomas in rats, without having a negative influence on body weight gain. After chemotherapeutic treatment no significant dietary influence was observed besides the high antineoplastic efficacy of HPC, but when feeding calorically restricted diets to surgically treated animals the number of reappearing tumours was considerably smaller (P = 0.06) than after feeding the diets ad libitum. The fat content of the diets did not influence the growth of manifest mammary carcinomas. No significant dietary effects were exerted on oestradiol or testosterone levels in untreated tumour bearing animals. An elevation of oestradiol levels was observed when animals were subjected to HPC and fed a high calorie diet. An elevation of testosterone levels was assessed after surgical treatment of the rats, irrespective of fat content and calorie level. Our results suggest that a reduction of calories can inhibit growth of manifest mammary carcinomas and has impeding effects on tumour development after surgical removal. After effective chemotherapeutic treatment the additional influence of dietary changes was of less relevance. Furthermore, our data do not establish any association between growth inhibition of mammary tumours, caused by the mild caloric restriction, and altered oestradiol or testosterone production. PMID- 1616857 TI - Changes in epidermal growth factor receptor expression and response to ligand associated with acquired tamoxifen resistance or oestrogen independence in the ZR 75-1 human breast cancer cell line. AB - We have examined the expression of receptors for epidermal growth factor (EGFR) by the ZR-75-1 human breast cancer cell line and tamoxifen resistant (ZR-75-9al 8 microM) and oestrogen independent/tamoxifen sensitive (ZR-PR-LT) variants. The parent line expressed a single class of high affinity binding sites (4,340 +/- 460 receptors/cell; Kd 0.23 +/- 0.04 nM). ZR-75-9al 8 microM cells, routinely maintained in medium containing 8 microM tamoxifen, were negative for oestrogen receptor (ER) and progesterone receptor (PGR) and expressed a markedly increased number of EGFR (14,723 +/- 2116 receptors/cell). Receptor affinity was unchanged. Time dependent reversal of the tamoxifen resistant phenotype was accompanied by a return to ER and PGR positivity and a fall in EGFR numbers to parent cell levels. In contrast ZR-PR-LT cells had a greatly reduced EGFR content (803 +/- 161 receptors/cell) accompanying elevated PGR numbers. Pre-treatment of these cells with suramin or mild acid stripping failed to expose receptors which may have been occupied by endogenously produced ligand. Increased proliferation of ZR-75-1 cells treated with EGFR (0.01-10 ng ml-1) was only observed in serum-free medium lacking insulin and oestradiol. Under these conditions untreated cells failed to proliferate. Both variant lines continued to proliferate in serum free medium in the absence or presence of insulin and oestradiol but failed to respond to exogenous EGF. PMID- 1616858 TI - Tumour proliferation assessed by combined histological and flow cytometric analysis: implications for therapy in squamous cell carcinoma in the head and neck. AB - The two techniques of flow cytometry analysis (FCM) and immunohistochemical localisation of bromodeoxyuridine (BrdUrd) incorporation after in vivo administration, were combined to study proliferation in squamous cell carcinoma of the head and neck region. Care was taken in this study to ensure that similar material was processed using both techniques such that comparisons could be made. FCM underestimated the labelling index (LI) in tumours classified as diploid compared to the histological evaluation of the tumour cells within those tumours (4.6% vs 17.1%). However, in aneuploid tumours, the FCM LI (10.7%) was similar to that obtained from histology (13.5%). Indeed, proliferation assessed by the combination of histology LI and FCM duration of S-phase (Ts) indicated that diploid tumours had a shorter median potential doubling time (Tpot) of 2.1 days compared to aneuploid (2.8 days). Despite the heterogeneity of proliferation evident histologically within the specimens, there was not a wide variation in the results of FCM analysis when multiple samples from resections were studied. Using FCM data alone, 46% of the tumours showed a Tpot of less than 5 days. When the Ts from the FCM data was combined with the average histological LI, 84% were less than 5 days and with the maximum LI, 99% were within this time interval. Compared with previous estimates, the proportion of tumours possessing proliferative characteristics which may indicate the need for acceleration of treatment seems to be much larger. PMID- 1616859 TI - Therapeutic effect of the gastrin receptor antagonist, CR2093 on gastrointestinal tumour cell growth. AB - The gastrin receptor antagonist, CR2093, competed with 125I-gastrin-17 (5 x 10( 10) M) for binding to gastrin receptors on the rat pancreatic adenocarcinoma, AR42J (CR2093 concentration inducing 50% of 125I-gastrin-17 binding (IC50) was 8 x 10(-5) M), on the human gastric adenocarcinoma, MKN45 (IC50 5.5 x 10(-5) M) and the human colo-rectal adenocarcinoma C523 (IC50 greater than 10(-4) M). Intravenous administration of CR2093 (40 mg kg-1 day-1) reduced the gastrin-17 stimulated growth of AR42J xenografts in nude mice to below that of the original basal growth (P = 0.0166 from basal and P = 0.0109 from gastrin stimulated growth). CR2093 administration also reduced the gastrin-stimulated growth of MKN45 xenografts (P = 0.045) but failed to inhibit the gastrin enhanced proliferation of C523 xenografts. This may be related to the affinity (Kd) of the gastrin receptors present on the xenograft lines as the Kds of the two xenografts inhibited by CR2093 were 4.6 x 10(-10) M (AR42J) and 1.2 x 10(-9) M (MKN45) respectively whereas the Kd of C523 was of higher affinity (2.2 x 10(-10) M). GR antagonists may be a viable therapeutic option for gastrin receptor positive, gastro-intestinal tumours. PMID- 1616860 TI - Oestrogen receptor negative-progesterone receptor positive phenotype in 1,211 breast tumours. AB - From 1,211 breast cancers, 15 oestrogen receptor (ER) negative-progesterone receptor (PgR) positive breast cancers by conventional dextran coated charcoal steroid binding assays in cytosol were reassessed using Elisa techniques with monoclonal antireceptors antibodies in the cytosolic and nuclear fractions, and immunocytochemistry on cryostat sections. Three categories of results were found in this series. Two tumours were false negative ER due to receptor sites occupancy by hormonal contraceptive treatment. A second group of ten tumours, with high PgR concentrations and immunoreactive ER, corresponds to non ER-binding forms of receptors. One PgR positive tumour was found to be devoid of PgR by using monoclonal antiPgR antibodies might contain a progesterone binding cyst protein. Only two tumours were found to be true ER negative-PgR positive by all methods. This rare phenotype deserves further study of the regulation of the PgR gene. PMID- 1616861 TI - MRI screening of kindred at risk of developing paragangliomas: support for genomic imprinting in hereditary glomus tumours. AB - Paragangliomas of the head and neck (glomus tumours) can occur in a hereditary pattern and may be hormonally active as well as being associated with paragangliomas elsewhere. A number of these tumours may be present without symptoms. To detect the presence of subclinical paragangliomas we screened 83 members of a family at risk of developing hereditary paragangliomas using whole body MRI and urinary catecholamine testing. In eight previously diagnosed members, eight known glomus tumours of which one functioning, and two unknown glomus tumours and one unknown pheochromocytoma were present. Six unsuspected members showed ten glomus tumours and one pheochromocytoma. It has been suggested that the manifestation of hereditary glomus tumours is determined by the sex of the transmitting parent. There were no tumours in the descendants of female gene carriers. Comparing the likelihood of inheritance with genomic imprinting versus inheritance without genomic imprinting we found an odds ratio of 23375 in favour of genomic imprinting. PMID- 1616862 TI - Late cardiopulmonary toxicity after treatment for Hodgkin's disease. AB - Cardiac and pulmonary functions were evaluated in 75 patients aged 50 years or under, treated for Hodgkin's disease by mantle radiotherapy at least 3 years earlier; all received the same mantle field radiotherapy: radiotherapy alone, MOPP chemotherapy plus radiotherapy, MOPP and ABVD chemotherapy plus radiotherapy. No patient had any symptom of heart disease. Only borderline abnormalities of ECG or echocardiogram were observed in 12 patients. One of them showed a moderate aortic stenosis which was known before the treatment; apical or septum hypokinesia were present in four patients and one patient had a slightly right ventricular dilatation. Twelve (16%) chest radiographs showed moderate or severe abnormalities, but there was no significant correlation between the results of pulmonary function tests and Xenon ventilation/perfusion scintigraphy, the clinical examination and the intensity of the radiological sequelae. Twenty nine (64%) Xenon scintigraphies showed a reduction of lung perfusion in the irradiated areas without any symptom. The resting mean pulmonary function test was significantly lower for the patients than for the control group with regard to Total Capacity and Vital Capacity. The exercise tolerance, as indicated by analysis of blood gases, was below the one expected for only two patients who were dyspneic during the low level of exercise. We did not find any significant difference between the three treatment groups. We conclude that the treatment with mantle field under good technical conditions (high energy photons, moderate doses...) can result in minimal cardiopulmonary dysfunction. PMID- 1616863 TI - A phase I study of regional 5-fluorouracil and systemic folinic acid for patients with colorectal liver metastases. AB - A phase I study was undertaken in order to establish the maximum tolerated dose of intra-hepatic arterial 5-fluorouracil (5-FU) when given in combination with systemic folinic acid. Patients with colorectal liver metastases (n = 10) received escalating doses of 5-FU as a 24 h infusion with a fixed dose (400 mg m 2) of intravenous folinic acid once per week. Dose limiting toxicity (WHO grade greater than 2) was encountered at 2 g m-2 5-FU. Principal adverse effects were diarrhoea, vomiting and oral ulceration. The recommended dose for phase II studies is 1.5 g m-2 week-1 24 h 5-FU regional infusion with 400 mg m-2 week-1 intravenous folinic acid. PMID- 1616864 TI - The relationship between skin cancers, solar radiation and ozone depletion. AB - During the period 1957-1984 the annual age-adjusted incidence rate of cutaneous malignant melanoma (CMM) increased by 350% for men and 440% for women in Norway. The annual exposure to carcinogenic sunlight in Norway, calculated by use of measured ozone levels, showed no increasing trend during the same period. Thus, ozone depletion is not a cause of the increasing trend of the incidence rates of skin cancers. The incidence rates of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) increase with decreasing latitude in Norway. The same is true for CMM in Norway, Sweden, and Finland. Our data were used to estimate the implications of a future ozone depletion for the incidence rates of skin cancer: a 10% ozone depletion was found to give rise to a 16-18% increase in the incidence rate of SCC (men and women), a 19% increase in the incidence rate of CMM for men and a 32% increase in the incidence rate of CMM for women. The difference between the numbers for men and women is almost significant and may be related to a different intermittent exposure pattern to sunlight of the two sexes. The increasing trend in the incidence rates of CMM is strongest for the trunk and lower extremities of women, followed by that for the trunk of men. The increasing incidence rates of skin cancers as well as the changing pattern of incidence on different parts of the body is most likely due to changing habits of sun exposure. Comparisons of relative densities of CMM, SCC, LMM and SCC falling per unit area of skin at different parts of the body indicate that sun exposure is the main cause of these cancer forms although other unknown factors may play significant roles as well. For the population as a whole sun exposure during vacations to sunny countries has so far been of minor importance in skin cancer induction. PMID- 1616866 TI - Analogues of LHRH versus orchidectomy: comparison of economic costs for castration in advanced prostate cancer. AB - Analogues of luteinising hormone releasing hormone (LHRH) have recently been introduced as an alternative to surgical orchidectomy in prostate cancer, but there has been concern about the economic costs of long-term treatment. The paper presents a comparison of costs for LHRH analogues versus orchidectomy in patients with advanced prostate cancer. The cost for the surgical procedure was estimated using data on patients treated with orchidectomy in Stockholm County, Sweden, during 1981-86. Estimates of costs for treatment with a depot LHRH analogue was based on observed treatment times among patients with symptomatic prostate cancer in a British randomised clinical trial of medical castration versus surgical orchidectomy. The average cost for orchidectomy was estimated at 2,580 pounds i.e. 7-31% less than for treatment with a depot LHRH analogue (2,760 pounds-3,380 pounds) assuming a mean treatment time in the range 19-23 months. The most cost effective policy for castration was found to be initial treatment with an LHRH analogue followed by deferred orchidectomy after about 2 years among long-term responders. This policy would obviate the need for surgery in about 85% of the patients and the average cost (1,900 pounds) would be about 26% lower compared to that of a policy of primary orchidectomy in all patients. PMID- 1616865 TI - Stage and delay in breast cancer diagnosis by race, socioeconomic status, age and year. AB - Information on 23,567 Non-Hispanic White, 2,539 Black, and 2,380 Hispanic breast cancer cases diagnosed between 1977 and 1985 was used to evaluate the risk of late stage diagnosis and long duration of symptoms prior to diagnosis in relation to ethnicity, socioeconomic status, age and year of diagnosis. All data were collected by the University of Southern California Cancer Surveillance Program, the comprehensive population-based incidence registry of Los Angeles County. The results indicate that lower socioeconomic status, Black or Hispanic ethnicity, younger age, and earlier year of diagnosis are risk factors for late stage diagnosis and long duration of symptoms. The effect of ethnicity was not explained by lower SES levels among Black or Hispanic women. After controlling for duration of symptoms, race and SES remained significantly predictive of more advanced stage. More recent diagnosis across the 9 year time frame was not associated with improved stage for those of low SES. These results suggest that increased efforts are needed to reach low SES and Black and Hispanic women with campaigns to improve the stage at which breast cancer is detected. PMID- 1616867 TI - Preventive Pap-smears: balancing costs, risks and benefits. AB - The pattern of spontaneous screening for cervical cancer by general practitioners and gynaecologists in The Netherlands is compared with an efficient screening policy resulting from a cost-effective study. Spontaneous screening tends to start and stop too early in a woman's life, and leaves too many women overscreened or unprotected. The combination in young age of a low incidence of invasive cancer and a high incidence of regressive lesions explains relative ineffectiveness and harmfulness of present screening practice. When screening would take place between ages 30 and at least 60, with intervals of about 5 years, as many lives could be saved for half the costs and with only 60% of the unnecessary referrals and treatments. Much attention should be paid to the coverage of the target population. Therapeutic follow-up policies for dysplastic lesions should be restrained. PMID- 1616868 TI - Guaiac and immunochemical tests for faecal occult blood in colorectal cancer screening. AB - Seven hundred and eighty-six subjects spontaneously referring to our Center performed two guaiac (Rehydrated Hemoccult II (R.HO), and Hemoccult Sensa (HO S.)), and two immunochemical (OC Hemodia (Hdia) and Hemeselect (Hsel)) faecal occult blood tests on three consecutive faecal determinations. The positivity rates of 3 day R.HO, HO S., Hdia, and Hsel were 4.8%, 5.6%, 8.4% and 11.2% respectively. One hundred and thirty-five of the 150 subjects with at least one positive test completed the diagnostic work-up. Cancer was detected in three subjects and adenomas in 15. Three-day specificity estimates of R.HO, HO S., Hdia and Hsel in the overall series were 96.1%, 96.0%, 93.8% and 91.2% respectively, the differences between guaiac and immunochemical tests being significant. Corresponding values of specificity as determined on the first faecal sample only in the overall series were 98.1%, 98.3%, 96.1% and 94.9% respectively. No significant difference in specificity is evident when 3-day guaiac tests are compared to 1-day immunochemical ones. Three-day immunochemical testing is not recommended for screening purposes due to its very low specificity. Nevertheless, 1-day immunochemical testing is almost as specific as 3-day guaiac testing. A preliminary estimate of colonic neoplasms detection rates shows no difference as well. The benefit of 1-day testing on screening acceptability is evident, but the impact on sensitivity should be evaluated in a screening situation with a proper study design and a larger sample size. PMID- 1616869 TI - Cyclical mastalgia as a marker of breast cancer susceptibility: results of a case control study among French women. AB - A matched case-control study in a population of urban, non-menopaused women living in Paris was performed between 1983 and 1985 to investigate the risk of breast cancer (BC) in relation to various factors with a particular interest in the effect of the use of oral contraceptive (OC) and the existence of cyclical mastalgia (CM). Two hundred and ten non-menopaused women, less than 45 years old, with newly diagnosed BC were compared to 210 controls from the same geographic area matched on year of birth, age, education level and age at first full term pregnancy (FFTP), when justified. The adjusted Relative Risk of BC (RRa) was significantly increased for a total duration of OC use longer than 72 months (RRa 2.80; 95% CI 1.56-5.01), as well as the RRa for OC use above 48 months before FFTP (3.26 95% CI 1.37-7.76) and, to a lesser extent, the RRa for OC use above 48 months after FFTP (2.02 95% CI 1.07-3.84) respectively. Adjustment was performed on familial history of BC, personal history of Benign Breast Disease (BBD), age at menarche. A previous history of cyclical mastalgia was found to be associated with an increased risk of BC. The significant increase remained after adjustment on the previously mentioned confounding factors and OC use: RRa 2.12; 95% CI (1.31-3.43). Under a precise definition related to the hormonal environment, mastalgia appear to be an interesting marker of breast cell susceptibility, the importance of which can only be validated by prospective studies. PMID- 1616870 TI - High-dose methotrexate in the treatment of malignant mesothelioma of the pleura. A phase II study. AB - From 1984 to 1989, 63 patients with diffuse, malignant mesothelioma of the pleura were treated with 4-8 courses of high-dose methotrexate (HDMTX, 3 g total dose) and citrovorum factor rescue. There were 61 male and two female patients of median age 60 years. CT scan was performed before and after treatment and used for response evaluation. Of 60 patients evaluable for response, 37% showed partial or complete remission, 32% showed no change and 32% showed progressive disease. Median survival from start of treatment for all patients was 11 months, for 42 patients with the epithelial type 12 months, and for 20 patients with sarcomatous or mixed types only 5 months. Toxicity was acceptable, with only five patients (8%) terminating therapy due to toxicity. One toxic death occurred. We conclude that HDMTX is an active regimen in malignant pleural mesothelioma. The significantly shorter survival for patients with the sarcomatous or mixed subtypes indicates that further investigations on the activity of HDMTX in mesothelioma should be limited to patients with the epithelial subtype. PMID- 1616871 TI - A method for assessing the quality of life of cancer patients: replication of the factor structure. AB - The psychometric properties of a method of measuring the quality of life of cancer patients based on multiple linear analogue scales have been assessed in a group of 294 patients with breast cancer attending one clinical unit. The method was found to be readily managed by patients although a small number of scales presented difficulties of understanding to patients and difficulties of analysis. The scales distinguished readily between patients of different disease and treatment status. Factor analysis revealed a 5 factor structure which we interpret as relating to physical activities of everyday living, emotional disturbance, alimentary disturbances, appearance and cosmetic problems and a fifth factor which is more difficult to interpret and includes impairment of speech, writing and concentration. We feel the essential factors determining quality of life in cancer patients have been demonstrated in this and our earlier studies and there is now a substantial level of agreement in the factors that have been identified by groups taking quite different approaches. The major factors determining quality of life in cancer patients are now known and should be assessed in clinical research and clinical trials. The method by which they should be assessed is not as yet so clear. PMID- 1616872 TI - Surgery in metastatic non-seminomatous germ cell tumours. PMID- 1616873 TI - Inverse relationship between ovarian aromatase cytochrome P450 and 5 alpha reductase enzyme activities and mRNA levels during the estrous cycle in the rat. AB - In the present study, we examined the changes in enzyme activity and mRNA levels of aromatase cytochrome P450 (P450AROM) and 5 alpha-reductase in ovarian tissue from adult cyclic rats. For each stage of the estrous cycle, the enzymatic activities were quantified by means of the 3H2O-release assay in the case of P450AROM and thin-layer chromatography in the case of 5 alpha-reductase. Levels of mRNA encoding P450AROM and 5 alpha-reductase in the ovary were determined by Northern blot analysis utilizing 32P-labeled rat cDNAs as probes. Serum LH levels were determined by RIA. Three P450AROM mRNA species were detected (at 1.7, 2.2 and 2.7 kb) in ovarian tissue from cyclic rats. All three P450AROM transcripts were expressed in a co-ordinated fashion throughout the cycle. The P450AROM levels were highest during diestrus and proestrus, decreased during estrus while at metestrus the levels were nearly nondetectable. Conversely, one 5 alpha reductase mRNA species at 2.5 kb was detected in ovarian tissue from cyclic animals. Ovarian 5 alpha-reductase mRNA levels were lowest during diestrus and proestrus, increased at estrus and were most abundant during metestrus; a pattern opposite to that of P450AROM. The pattern of change in P450AROM and 5 alpha reductase activities paralleled that of the respective mRNA profiles but lagged behind the mRNA profiles by about 24 h, or one stage of the estrous cycle. Aromatase activity was 1.5 pmol/h/mg protein during diestrus, increased over 3 fold at proestrus (approximately 5.5 pmol/h/mg protein), decreased at estrus and declined to the lowest values at metestrus (approximately 1.0 pmol/h/mg protein). In contrast, the 5 alpha-reductase activity pattern was essentially the mirror image of the P450AROM activity pattern during the estrous cycle. 5 alpha Reductase levels were lowest during proestrus (approximately 5 pmol/h/mg protein) and estrus (approximately 8 pmol/h/mg protein), increased over 3-fold during metestrus, while the highest activity levels occurred during diestrus (approximately 36 pmol/h/mg protein). The normalization of the P450AROM and 5 alpha-reductase mRNA levels and their respective enzyme activities revealed a correspondence between mRNA abundance and subsequent increases (24 h later) in enzyme activity levels during the estrous cycle. These findings suggest that: (a) a temporal relationship exists between the profiles of the enzymatic activities that follows the changes in the levels of their respective mRNAs and (b) an inverse pattern exists between P450AROM and 5 alpha-reductase in terms of both enzymatic activity and mRNA expression during the estrous cycle in rat. PMID- 1616874 TI - Effects of transforming growth factors and regulation of their mRNA levels in two human endometrial adenocarcinoma cell lines. AB - The effects of the transforming growth factor-beta 1 (TGF-beta 1) and epidermal growth factor (EGF) on the growth of cells from 2 endometrial cancer lines, Ishikawa and HEC-50 were evaluated by measuring rates of DNA synthesis and changes in cell numbers during culture. EGF at 17 and 1.7 nM concentrations consistently enhanced HEC-50 cell proliferation. TGF-beta 1 inhibited Ishikawa cell proliferation but, unexpectedly for epithelium-derived cells, stimulated HEC 50 cell growth. This effect is of interest as it indicates that endometrial cells can acquire an altered responsiveness to a growth inhibitor during the process of malignant transformation. Northern blot analyses showed expression of TGF-alpha, TGF-beta 1 and EGF receptors mRNA in both cell lines. Neither estradiol (E2) nor 4-hydroxytamoxifen (OHTam) affected mRNA levels for either TGF-alpha or TGF-beta in HEC-50 cells, a line unresponsive to E2 for proliferation. In Ishikawa cells, previously shown to respond to both E2 and OHTam by increasing proliferation rates, E2 increased TGF-alpha mRNA and reduced TGF-beta mRNA levels. OHTam lowered the levels of both mRNA species, although the effect was greater on TGF beta than TGF-alpha mRNA. These data are consistent with, but do not prove, the existence of a possible autocrine regulation by TGF-alpha and TGF-beta of human cancer cell proliferation, which might be under E2 influence in Ishikawa cells. PMID- 1616875 TI - Effects of progestins on the proliferation of estrogen-dependent human breast cancer cells under growth factor-defined conditions. AB - The effect was studied of four different synthetic progestins (Org 30659, gestodene, 3-ketodesogestrel and levonorgestrel) on the proliferation of the 17 beta estradiol (E2)-dependent human breast cancer cell line MCF7. All progestins were found to stimulate proliferation, but only at high pharmacological dosages. Moreover, like estrogens the progestins at high concentrations synergistically stimulated MCF7 cell proliferation together with low concentrations of insulin. This stimulatory effect could be blocked by antiestrogens, but not by antiglucocorticoids and antiprogestins. This suggests that growth stimulation by these progestins (or their metabolites) occurs through crossreaction with the E2 receptor (ER). This is confirmed by the observation that the strong synthetic progestin Org 2058 does not stimulate proliferation. The absence of a progesterone receptor (PR)-mediated growth response seems not to be due to aberrant PR expression in these cells; 27,000 receptors (Kd 1.7 x 10(-10)M) per cell were present under growth-assay conditions. Growth stimulation by E2 in the absence or presence of insulin, is slightly inhibited or unaffected by the progestins, respectively. Our data do not support a role for the recently identified gestodene binding sites [Colletta et al., J. Steroid Biochem. 33 (1989) 1055-1061] in mediating gestodene effects on breast cancer cells: gestodene and 3-ketodesogestrel, a compound that does not bind to these gestodene binding sites, showed a similar biological activity. The effects of the progestins on the MCF7 breast cancer cell line, indicate that the use of these compounds at very high concentrations may be unfavourable, but do not support a role for them in directly stimulating breast tumor proliferation at the low progestin concentration which are reached in the serum in oral contraceptive users. PMID- 1616876 TI - Comparison of the carbohydrate composition of rat and human corticosteroid binding globulin: species specific glycosylation. AB - We have examined the carbohydrate composition of corticosteroid-binding globulin (CBG) obtained from rat and human serum. Rat CBG contained a carbohydrate composition that was strikingly different from that of human CBG. Like other glycoproteins that circulate in human plasma, human CBG had a carbohydrate composition that was consistent with the presence of biantennary and triantennary oligosaccharide structures. In contrast, the carbohydrate composition of rat CBG indicated the presence of more than one sialic acid residue per antenna. It is not clear whether rat CBG contains a carbohydrate structure with sialic acids attached to both galactose and N-acetylglucosamine on the same antenna, or a terminal disialylated structure (sialic acid linked alpha 2-8 to sialic acid). These structural variations may play a role in the interaction of CBG with its receptor. PMID- 1616878 TI - Stress-induced changes of glucocorticoid receptor in rat liver. AB - The effect of corticosterone injection and of acute and repeated stress on rat liver cytosol glucocorticoid receptor was studied to ascertain whether corticosterone-induced glucocorticoid receptor (GR) regulation also takes place in intact animals as it does in adrenalectomized ones. Adult male rats were exposed to six different stressors (swimming, 10 mg/kg histamine i.p., 500 mU/kg vasopressin s.c., heat, immobilization and cold) acutely or three times daily for 18 days (repeated stress). Each of the stressors applied acutely provoked a pronounced increase of plasma corticosterone with subsequent induction of hepatic tyrosine aminotransferase activity. Depletion of cytosol receptor was however only noticed after swimming and histamine injection. On the other hand, sustained hypersecretion of corticosterone evoked by repeated stress significantly reduced the number of GR in rat liver cytosol without any change in Kd. It is concluded that in the presence of intact adrenal glands cytosol receptors are more resistant to corticosterone-induced depletion than in their absence. Further, repeated stress causes down-regulation of GR in the liver, most probably by sustained corticosterone secretion, yet the effect of other stress factors cannot be excluded. PMID- 1616877 TI - Stimulatory and inhibitory effects of progesterone on FSH secretion by the anterior pituitary. AB - The purpose of this study was to investigate whether progesterone exerted progesterone receptor mediated direct effects on the anterior pituitary in the secretion of FSH and whether such effects were mediated through the 5 alpha reduction of progesterone. Treatment of anterior pituitary dispersed cells for 48 h with 0.5 nM estradiol reduced the ED50 for gonadotropin releasing hormone (GnRH)-stimulated FSH release from 0.58 to 0.36 ng/ml and the ED50 for GnRH induced LH release from 0.54 to 0.19 ng/ml. When dispersed pituitary cells were treated with 0.5 nM estradiol and exposed to various doses of progesterone for 1 to 6 h, the most consistent rise in basal and GnRH-stimulated FSH release was observed with the 50 nM dose of progesterone with a 3-h exposure period. All three doses of progesterone elevated basal LH and GnRH-stimulated LH was increased by the 50 and 100 nM doses of progesterone during the 3-h period of treatment. Using the 50 nM dose of progesterone, basal and GnRH-stimulated LH was increased after 2, 3 and 6 h of progesterone treatment. When the period of exposure of progesterone was extended to 12, 36 or 48 h, there was a significant inhibition of GnRH-stimulated FSH release. GnRH-stimulated LH release was inhibited at 36 and 48 but not 12 h after progesterone treatment. These studies showed that the effect of progesterone administered for periods of 1 to 6 h enhanced the secretion of LH and FSH whereas progesterone administered for periods beyond 12 h inhibited FSH and LH release by dispersed pituitary cells in culture. These results are similar to those observed in vivo after progesterone treatment. Furthermore estrogen priming of the dispersed pituitary cells was necessary to observe the effects of progesterone. The progesterone antagonist RU486 prevented the progesterone-induced rise in GnRH-stimulated FSH release. Furthermore the 5 alpha-reductase inhibitor N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane- 17 beta-carboxamide also prevented the progesterone-induced rise in GnRH-stimulated FSH release in estrogen-treated dispersed pituitary cells. These results indicate that the anterior pituitary is a major site of action of progesterone in the release of FSH and that 5 alpha-reduction of progesterone plays an important role in FSH release. PMID- 1616879 TI - Ontogenic development of liver progesterone metabolism in female sheep. Contribution of cytochrome P4502B and P4503A subfamilies. AB - Age-related changes in progesterone hepatic metabolism were measured in Lacaune ewes in the foetal, neonatal (1 and 4 weeks), growing (7 months), pregnant (11 months) and adult (6 years) stages. 6 beta-Hydroxylation and 20 alpha-reduction were found to be the most efficient metabolic process in ovine microsomes. These activities were detected in 3-month-old foetuses and they increased rapidly during the first month of life, in a similar manner to the developmental expression of the cytochrome P4503A subfamily. 16 alpha- and 21-hydroxylation of progesterone were characterized by low, constant turn over in sheep liver microsomes during development. The hepatic ovine P4502B isozyme was purified to electrophoretic homogeneity by means of successive DEAE cellulose, hydroxylapatite and CM cellulose chromatographic separations. This hemoprotein had an apparent molecular weight of 51 kDa and was characterized by spectral data, NH2-terminal amino-acid sequence, immunological and catalytic properties. The relative contribution of this form and of the previously purified ovine P4503A subfamily was investigated in liver progesterone metabolism by immunoinhibition studies using polyclonal antibodies raised in rabbits and from the existence of induction and of significant correlations between microsomal activity and specific P450 content. In sheep liver microsomes, it would appear that cytochrome P4502B is involved in progesterone 21-hydroxylation whereas P4503A participates in the 6 beta- and 16 alpha-hydroxylation and possibly in the reductive conversion of progesterone in its 20 alpha-hydroxy derivative. PMID- 1616880 TI - Selective inhibition of the 5 alpha-reductase of the rat epididymis. AB - The effect of several synthetic steroids belonging either to the 4-aza-3-oxo steroid family or to androstene and androstane derivatives was investigated "in vitro" on the epididymal as well as prostatic 5 alpha-reductase activity. For this purpose rat caput epididymis and prostate were incubated with the different steroidal compounds at molar concentrations of 10(-7), 10(-6), and 10(-5) in the presence of labelled testosterone as substrate. The steroids 4-MA (17 beta, N,N diethyl-carbamoyl-4-aza-5 alpha-androstan-3-one) and 4-OH-A (4-hydroxy androstenedione), already known to be effective 5 alpha-reductase inhibitors at the level of the prostate, have been used as reference molecules. The 5 alpha reductase activity was evaluated by measuring pg of dihydrotestosterone (DHT) formed in 2 h of incubation by mg of tissue. The steroids A, B, C, F, G and I inhibit the formation of DHT in the rat epididymis although to different extents; they are also equally effective on the formation of DHT in the rat prostate. The steroids D, E, H and L are devoid of any inhibitory property on the formation of DHT in both the rat epididymis and prostate. The most interesting results were obtained with compound M which exhibits a dose-dependent and significant inhibitory effect on the formation of DHT in the epididymis, but it is inactive at the level of the prostate. These findings suggest that it is possible (a) to selectively interfere with the 5 alpha-reductase of the epididymis without affecting that present in the prostate, and (b) consequently to envisage new ways to regulate male fertility. PMID- 1616881 TI - Transformation and nuclear translocation of brain type L corticosteroid receptors complexed with the mineralocorticoid antagonist ZK 91587, aldosterone or dexamethasone. AB - Type I corticosteroid receptors were determined in cytosol from hippocampus (HIPPO) and amygdala (AMYG), using [3H]aldosterone (ALDO), [3H]dexamethasone (DEX) or the mineralocorticoid antagonist [3H]ZK 91587 as ligands. Incubations with the first two compounds also contained the pure glucocorticoid RU 28362 to block type II receptors. Binding of the three ligands was comparable in cytosol from HIPPO and it was slightly higher for [3H]DEX in AMYG. However, after heat induced receptor transformation, binding to DNA-cellulose was observed for [3H]ALDO-receptor complex obtained from HIPPO or AMYG, whereas it was negligible for [3H]ZK 91587. Receptors charged with [3H]DEX or [3H]ALDO showed similar retention on DNA-cellulose columns in the case of the AMYG, while binding to the polynucleotide was higher for [3H]ALDO in the HIPPO. Finally, only [3H]ALDO was taken up to a significant extent in purified cell nuclei prepared from slices of HIPPO and AMYG previously incubated with the three ligands. It is concluded that binding of a natural agonist steroid may be a prerequisite for type I receptor transformation and translocation from the cytoplasm into the nuclear fraction. DEX binding to type I receptors resembles a partial agonist with antagonist properties, whereas antagonists such as ZK 91587 are bound and retained in cytoplasm, without further translocation. PMID- 1616882 TI - Substrate specificity of cholesterol oxidase from Streptomyces cinnamomeus--a monolayer study. AB - The substrate specificity of cholesterol oxidase from Streptomyces cinnamomeus was examined in oriented sterol monolayers at the air/water interface. Of the cholesterol analogues with structural alterations in the A- or B-ring that were examined, it was observed that 5 alpha-cholestan-3 beta-ol was oxidized almost as fast as cholesterol itself. When the delta-5 double bond in cholesterol was instead at the delta-4 position, the oxidation rate became 3.2-fold slower. A similar reduction in the average oxidation rate was observed when the delta-5 double bond in cholesterol was instead at the delta-7 position (5 alpha-cholest-7 en-3 beta- ol). 5,7-Cholestadien-3 beta-ol was oxidized 5.1-fold slower compared to cholesterol, whereas 3 beta-hydroxy-5-cholesten-7-one and 5 beta-cholestan-3 beta-ol were not substrates of the enzyme (also verified from the lack of H2O2 production). With C(17) side chain analogues of cholesterol, it was observed that the complete lack of the C(17) side chain (5-androsten-3 beta-ol), or the insertion of an unsaturation at delta-24 (desmosterol), or even an ethyl group at C(24)(24b-ethyl-5,22- cholestadien-3 beta-ol) had no appreciable effects on sterol oxidation rate, implying that the enzyme did not recognize the side chain in oriented sterol monolayers. This study has shown that the sterol monolayer system is a good technique to examine sterol/cholesterol oxidase interactions, since both the orientation of the substrate molecules, and the quality of the interface can be mastered. PMID- 1616883 TI - Studies on anabolic steroids--12. Epimerization and degradation of anabolic 17 beta-sulfate-17 alpha-methyl steroids in human: qualitative and quantitative GC/MS analysis. AB - The epimerization and dehydration reactions of the 17 beta-hydroxy group of anabolic 17 beta-hydroxy-17 alpha-methyl steroids have been investigated using the pyridinium salts of 17 beta-sulfate derivatives of methandienone 1, methyltestosterone 4, oxandrolone 7, mestanolone 10 and stanozolol 11 as model compounds. Rearrangement of the sulfate conjugates in buffered urine (pH 5.2) afforded the corresponding 17-epimers and 18-nor-17,17-dimethyl-13(14)-enes in a ratio of 0.8:1. These data indicated that both epimerization and dehydration of the 17 beta-sulfate derivatives were not dependent upon the respective chemical features of the steroids studied, but were instead inherent to the chemistry of the tertiary 17 beta-hydroxy group of these steroids. Interestingly, in vivo studies carried out with human male volunteers showed that only methandienone 1, methyltestosterone 4 and oxandrolone 7 yielded the corresponding 17-epimers 2, 5 and 8 and the 18-nor-17,17-dimethyl-13(14)-enes 3, 6 and 9 in ratios of 0.5:1, 2:1 and 2.7:1, respectively. No trace of the corresponding 17-epimers and 18-nor 17,17-dimethyl-13(14)-enes derivatives of mestanolone 10 and stanozolol 11 was detected in urine samples collected after administration of these steroids. These data suggested that the in vivo formation of the 17-epimers and 18-nor-17,17 dimethyl-13(14)-enes derivatives of 17 beta-hydroxy-17 alpha-methyl steroids is also dependent upon phase I and phase II metabolic reactions other than sulfation of the tertiary 17 beta-hydroxyl group, which are probably modulated by the respective chemical features of the steroidal substrates. The data reported in this study demonstrate that the 17-epimers and 18-nor-17,17-dimethyl-13(14)-enes are not artifacts resulting from the acidic or microbial degradation of the parent steroids in the gut as previously suggested by other authors, but arise from the rearrangement of their 17 beta-sulfate derivatives. Unchanged oxandrolone 7 was solely detected in the unconjugated steroid fraction whereas unchanged steroids 1, 4 and 11 were recovered from the glucuronide fraction. These data are indirect evidences suggesting that the glucuronide conjugates of compounds 1 and 4 are probably enol glucuronides and that of compound 11 is excreted in urine as a N-glucuronide involving its pyrazole moiety. The urinary excretion profiles of the epimeric and 18-nor-17,17-dimethyl-13(14)-ene steroids are presented and discussed on the basis of their structural features. PMID- 1616884 TI - Effects of dihydrotestosterone and hydroxyflutamide on androgen receptors in cultured human breast cancer cells (EVSA-T). AB - The purpose of our study was to evaluate the effects of 5 alpha dihydrotestosterone (DHT) and hydroxyflutamide (HF), alone or in combination, on androgen receptor (AR) dynamics and on cellular growth in cultured breast cancer cells (EVSA-T). The incubation of cells with DHT increased the concentration of nuclear AR after 24 and 48 h. HF was also able to promote the nuclear accumulation of AR after 24 and 48 h of treatment. When HF-treated cells are incubated with DHT, the nuclear AR concentration is lower than that found in cells treated with DHT alone. We conclude that HF acts by increasing nuclear accumulation of receptor-antiandrogen complexes. Moreover, DHT stimulates cell growth while HF has an inhibitory effect. Thymidine incorporation in cells also increased after DHT treatment and decreased after HF incubation. The HF-induced inhibition of cell growth persisted both after renewal of the medium and after the addition of DHT to cultures. It may be hypothesized that either DHT is converted to inactive metabolites or that HF exerts a persistent inhibitory effect. In the latter case, the antiandrogen action of HF could be exerted by retention of high levels of antiandrogen in cells or by such a depressed protein synthesis that the renewal of growth is slower than the 48 h period studied. PMID- 1616885 TI - Cancer research funding: good news from the U.S., bad news from Europe. PMID- 1616886 TI - Hormone refractory metastatic prostate cancer. PMID- 1616887 TI - The impact of pharmacokinetically guided dose escalation strategies in phase I clinical trials: critical evaluation and recommendations for future studies. AB - Phase I studies requiring multiple dose escalation steps have led to the development of pharmacokinetically guided dose escalation (PGDE) strategies to expedite the conduct of early clinical trials. This article critically reviews PGDE strategies for a number of new anticancer agents including amphethinile, brequinar sodium, iodo-doxorubicin, the anthrapyrazoles (DuP 941, DuP 942 and DuP 937), rhizoxin, and aphidicolin glycinate. The benefits and problems associated with PGDE are examined. Recommendations are made for the optimal deployment of pharmacological information in future phase I studies. PMID- 1616888 TI - AACR/EACR first joint conference: concepts and molecular mechanisms of multistage carcinogenesis. PMID- 1616889 TI - Prognostic factors in hormone-resistant progressing cancer of the prostate. AB - In 224 consecutive patients with hormone-resistant prostatic cancer referred to 2 European Cancer Centres for palliation of painful bone metastases the one year survival for all patients was 24% (2-year survival: 7%). The median survival was 8 months. In univariate analyses the following prognostic factors were identified: performance status, serum creatinine, alkaline phosphatase, duration of response to primary hormone treatment, degree of bone scan involvement and hemoglobin. Multivariate analyses confirmed the four first parameters to be independent factors. A prognostic model was established (no or one risk factors vs 2 risk factors vs 3 or 4 risk factors) based on performance status, creatinine, alkaline phosphatase and hormone response duration. The median survival of these groups was 10 months, 6 months and 3 months, respectively. This model proved to be discriminative in an external data set of 214 patients with hormone-resistant prostatic cancer entered in two prospective trials. The above differences in outcome between readily and simply defined prognostic groups are greater than the differences one can realistically hope to produce using new treatment strategies. These prognostic factors should be taken into account both in the design and interpretation of clinical studies dealing with the treatment of hormone-resistant progressing prostatic cancer and painful bone metastases. PMID- 1616890 TI - Fluorouracil-alone versus high-dose folinic acid and fluorouracil in advanced colorectal cancer: a randomized trial of the Italian Oncology Group for Clinical Research (GOIRC). AB - One hundred eighty-one patients with measurable recurrent or metastatic colorectal cancer, who had not received prior chemotherapy, were randomized in a prospective controlled trial to receive 5-fluorouracil (5FU), 13.5 mg/kg, for five days (arm A) or high-dose folinic acid [Cyanamid-Lederle, Italy] (FA), 200 mg/m2, for five days and 5FU, 400 mg/m2 for five days (arm B). The treatments were repeated every four weeks. One hundred fifty-five patients were evaluable for response. The two arms were balanced for all potential prognostic factors studied. The response rate (CR+PR) was 18% in the 5FU arm and 16% in the 5FU plus FA arm. Median duration of response was 56 weeks for 5FU alone and 42 weeks for the combination (p = 0.48). Median time to failure (TTF) was 20 weeks for arm A and 21 for arm B (p = 0.62). Median survival was 62 weeks on the 5FU arm and 53 weeks on the FA plus 5FU arm (p = 0.14). Dose intensity (DI) delivered was the same in both arms. Diarrhea and mucositis were the most frequent adverse reactions in arm B; 20% of the patients in arm A and 38% of those in arm B experienced diarrhea (p = 0.008). Mucositis occurred in 34% of patients in arm A and 42% in arm B (p = 0.04). In general nausea and vomiting were moderate. Hematological toxicity was more severe in patients treated with 5FU alone: 31% in arm A and 14% in arm B developed leukopenia (p = 0.015). In the combination arm one patient died due to gastrointestinal and hematological toxicity after the seventh cycle. This study indicates that, in advanced colorectal cancer, the combination of high-dose FA and 5FU is not superior to 5FU alone when utilized at standard high-dose intensity. PMID- 1616892 TI - Non-Hodgkin's lymphoma in the elderly. A study of 602 patients aged 70 or older from a Danish population-based registry. The Danish LYEO-Study Group. AB - Within a 7-year period 1,597 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) were included in a Danish population-based NHL registry. Of these, 602 (38%) were aged 70 years or older (age range 70-94, median: 76.8). They represent the population defined as 'elderly' patients in the present study. The average annual incidence rate for this elderly patient population was 35.7/10(5), as compared with 6.6/10(5) for patients aged less than 70 (overall annual incidence: 9.5/10(5)). Localised cases (stage I and II) and extranodal manifestations were found more frequently among elderly patients. The most common sites of extranodal involvement were the stomach (21% of all extranodal cases) and the bone marrow (16%). Histologically, follicular centroblastic/centrocytic cases were found to be less frequent (p less than 0.01) in elderly patients as compared to their younger counterparts (less than 70 years), who in contrast had a lower occurrence of diffuse centroblastic cases (p less than 0.01). Overall 7-year survival for the elderly patient population was 35% (median 1.7 years), and for patients aged less than 70 it was 57%. This difference persisted after correction for apparently NHL-unrelated deaths (52% vs. 66%, respectively, p less than 0.0001). Elderly patients with poor prognosis were characterised by the following features identified in a Cox-regression model: hepatic involvement, presence of B symptoms, high-grade histology and elevated s-LDH. The corresponding relative risk values were in the order 2.4, 2.2, 1.9 and 1.6. PMID- 1616891 TI - Teniposide in advanced breast cancer. A phase II trial in patients with no prior chemotherapy. AB - The objective response rates were determined using teniposide as first-line chemotherapy for patients with recurrent breast cancer. Twenty-seven evaluable patients with advanced disease received teniposide 70 mg/m2 i.v. days 1-5 every 3 weeks. A total of 211 courses were given. Responses included one complete (4%) and 9 partial responses (33%) with a median duration of response of 9 months (range 2-31 months). The main toxicity was myelosuppression. The results show that teniposide has at least modest activity in patients with advanced breast cancer treated previously with endocrine therapy. PMID- 1616893 TI - Steroid receptor status in malignant and non-malignant larynx. AB - We investigated for the first time the relationships among all the different steroid receptor classes and between steroid receptor status and lymph node involvement in laryngeal carcinoma. Androgen (AR), oestrogen (ER), progesterone (PR) and glucocorticoid (GR) receptors were assayed in the high-speed soluble fraction and in the nuclear extract from 73 carcinomas of the larynx. Forty-one, 26, 15, and 13 tumours expressed cytosolic GR, ER, AR, and PR, respectively, while 33, 26, 13 and 13 biopsies were nuclear-positive for GR, ER, AR, and PR, respectively. Data obtained in histologically-proven non-cancerous larynx (N = 20) compared to those obtained in the malignant specimens showed a significant loss of ER and PR in cancerous larynx over that in the non-cancerous tissue. Lymph node metastases were evaluated in only 53 of the 73 patients and they were noted in 22 cases (41.5%). No significant relationships were found either among the different classes of steroid receptors or between steroid receptors and lymph node involvement. Despite the apparent absence of any interrelationships among the different receptors or tendency towards metastasis, the presence of steroid receptors would justify the use of hormonal manipulations which could be effective in the management of this disease. PMID- 1616895 TI - Phase II trials of fosquidone (GR63178A) in carcinoma of the breast, head and neck, ovary and melanoma. AB - A total of 91 eligible patients with metastatic cancer have been treated in a series of phase II trials of the novel pentacyclic pyrroloquinone, fosquidone. Tumour types were breast (24), ovary (25), head and neck (21) and melanoma (21). All patients, except those with melanoma had received prior chemotherapy. The drug was given intravenously as a 20 min infusion, at the dose of 120 mg/m2 on days 1 to 5 of a 3 week cycle. Treatment was well tolerated; the only significant side-effects being mild headaches and generalised musculo-skeletal pains. Response was assessed after 2 cycles of therapy. Only one patient (with head and neck cancer) achieved an objective partial response, lasting 6 weeks. A total of 12 patients demonstrated stable disease for a median duration of 15 to 20 weeks. Using this schedule of administration, fosquidone has no significant antitumour activity in this group of tumours. PMID- 1616894 TI - Treatment related psychological distress during adjuvant chemotherapy as a conditioned response. AB - Patients receiving cycles of cytotoxic chemotherapy for cancer often experience noxious side effects following treatments and may develop classically conditioned side effects, such as anticipatory nausea and vomiting (ANV) during the course of repeated infusions. The present study explored the possibility that classical conditioning processes may also contribute to treatment related psychological distress. Sixty-six patients, scheduled for adjuvant chemotherapy for breast cancer (stages I, II, IIIa), agreed to participate. Patients were assessed in the clinic on the first day of every chemotherapy cycle and in their homes three to five days before their final cycle. Patients experienced considerable psychological distress during the course of chemotherapy, and particularly before the first infusion. Prior to the last cycle of chemotherapy, psychological distress was significantly higher in the clinic environment than in patients' homes. Consistent with classical conditioning, psychological distress did not escalate over the days before treatment, but rather increased abruptly when patients returned to the clinic. The results of the present study indicate that several factors are involved in patients' anticipatory psychological distress and highlight the potential contribution that conditioning processes may make to patients' emotional distress in the clinic environment. PMID- 1616896 TI - Intracranial meningioma with metastatic breast carcinoma. PMID- 1616897 TI - Crosslinking of the cell surface immunoglobulin (mu-surrogate light chains complex) on pre-B cells induces activation of V gene rearrangements at the immunoglobulin kappa locus. AB - We constructed an expression vector encoding a truncated Ig mu chain that lacks both VH and CH1 domains (mu delta m chain) and introduced the mu delta m vector into the Ig negative Abelson pre-B cell line P17-27. The transfectants expressed a large amount of the mu delta m chain on their surface, which was not complexed with the lambda 5 and VpreB surrogate light chain molecules. While P17-27 transfected with a vector for the intact micron chain (P17-27 micron) shows V kappa rearrangements in culture, V kappa rearrangements were not detected in P17 27 mu delta m cells. When the mu delta m chains on the cell surface were crosslinked by anti-mu antibodies, V kappa gene rearrangements were induced in P17-27 mu delta m. These results strongly suggest that crosslinking of the micron lambda 5-VpreB complex on the pre-B cell surface generates a signal that activates V kappa gene rearrangement, and that the lambda 5 and VpreB molecules are necessary for the spontaneous crosslinking of surface Ig on pre-B cells. PMID- 1616898 TI - Reversal of in vitro T cell clonal anergy by IL-2 stimulation. AB - Stimulation of a normal type I mouse T helper cell clone (TH1) with concanavalin A in the absence of antigen presenting cells (APC) in vitro results in the induction of a hyporesponsive state known as T cell clonal anergy. This state is characterized by a decrease in proliferation following stimulation with antigen and APC resulting from a decrease in the production of IL-2. Production of the lymphokines IL-3/granulocyte macrophage colony stimulating factor and IFN-gamma is also reduced, although to a lesser degree. Stimulation of such anergic cells with IL-2 results in proliferation and a complete reversal of the state. We demonstrate that this reversal is not due to the outgrowth of a subpopulation of cells that had escaped anergy induction, but rather occurs in all the cells. Anergy also dissipated spontaneously, although much more slowly, in the absence of T cell antigen receptor occupancy. Finally, we show that a similar state can be produced by normal activation with antigen and APC if IL-2 and other factors are removed at 16-20 h. These results indicate that the anergic state is not a permanent change in the TH1 cell. Anergy induction appears to be a consequence of the inability of the cell to divide extensively following stimulation through the antigen-specific receptor. We propose a model to explain these results in terms of a relatively stable negative regulatory factor. PMID- 1616899 TI - Secretion and function of the third component of complement (C3) by murine leukocytes. AB - Our new finding of de novo synthesis and secretion of C3 by both murine peritoneal macrophages and polymorphonuclear leukocytes (PMN) was confirmed by the incorporation of [35S]methionine into C3 molecules and their complete inhibition by cycloheximide. The methods of secretion of C3 from these two types of cells were compared by examining the C3 contents in their culture supernatants. Completely different modes of secretion were observed, i.e. although macrophages synthesize and secrete C3 constitutively, PMN has a mechanism to store the already synthesized C3 in the cell and secrete it in response to stimuli. Protein kinase C (PKC) activators, e.g. 12-O-tetradecanoyl phorbol 13-acetate, dioctanoyl glycerol, and mezerein, as well as calcium ionophore A23187 stimulate the secretion of C3 from PMN. These results suggest the involvement of PKC and the calmodulin pathway. A very sensitive method for measuring C3 activity was developed which enabled us to show for the first time that C3 secreted by PMN had opsonizing activity and that particles cultured with PMN were phagocytosed effectively. PMID- 1616900 TI - The lineage relationship between virgin and memory B cells. AB - J11d is expressed on a variety of hemopoietic cells, including B cells. In previous studies, we have shown that B cells are heterogeneous with respect to their levels of J11d expression and that memory B cells are contained within the J11dlo B cell population. In this report, we have further examined the relationship between memory precursors and memory cells. We have found that the ability of J11dlo B cells from unprimed mice to respond to primary antigenic stimulation was generally low; the lowest response occurred following immunization with soluble antigen in vitro. Following adoptive transfer into irradiated mice and repeated stimulation of these mice with antigen, J11dlo cells generated memory responses which were similar to those generated by J11dlo memory cells obtained from primed mice. In contrast, J11dhi B cells from unprimed mice gave rise to both primary and memory responses, but the memory responses were lower than those generated by J11dlo cells. Although the expression of J11d on both J11dhi and J11dlo cells from unprimed mice decreased after adoptive transfer, J11dlo, as compared to J11dhi, virgin cells proliferated more rapidly. These results suggest that memory responses are elaborated predominantly from J11dlo virgin cells. Taken together with previous results, our studies indicate that, J11dlo B cells are different from J11dhi B cells. Hence, they are either memory precursors or are memory cells. PMID- 1616901 TI - Does body fatness modify the association between dietary cholesterol and risk of coronary death? Results from the Chicago Western Electric Study. AB - The hypothesis that body fatness modifies the relation between dietary cholesterol and 25-year coronary mortality was examined in a cohort of 1,792 middle-aged men employed by the Western Electric Company in Chicago. Relative risks of coronary death (and 95% confidence intervals) associated with a 225 mg/day greater intake of dietary cholesterol for men with a subscapular skinfold thickness less than or equal to 14, 15-20, and greater than or equal to 21 mm were 1.44 (1.10-1.90), 1.07 (0.84-1.36), and 0.95 (0.76-1.20), respectively, after adjustment for age; serum total cholesterol level; systolic blood pressure; cigarette smoking; family history of cardiovascular disease; evidence of major organ system disease at baseline; and intake of saturated fatty acids, polyunsaturated fatty acids, energy, and ethanol. Adjusted relative risks associated with a 15-mm greater subscapular skinfold thickness for men with a dietary cholesterol intake less than or equal to 649, 650-799, and greater than or equal to 800 mg/day were 1.76 (1.04-2.98), 1.64 (1.04-2.57), and 1.00 (0.69 1.55), respectively. Fatter men apparently did not benefit from a diet lower in cholesterol, while men who ate a diet high in cholesterol apparently did not benefit from leanness. These results support the hypothesis that body fatness modifies the relation between dietary cholesterol and coronary mortality, perhaps because leaner men are more responsive than fatter men to the effects of dietary cholesterol on the concentration of low density lipoprotein cholesterol. PMID- 1616902 TI - Accelerated cholesterol accumulation in homologous arterial transplants in cholesterol-fed rabbits. A surgical model to study transplantation atherosclerosis. AB - Accelerated coronary artery disease has become a major complication to heart transplantation in humans. Therefore, we have developed a surgical model in the rabbit, with transplantation of the thoracic aorta as a bypass graft onto the abdominal aorta of another rabbit. The model permits the study of cholesterol metabolism in transplanted arteries. The graft did not accumulate cholesterol for as long as 298 days, provided that the rabbits were normocholesterolemic, i.e., with plasma cholesterol levels of 0.3-0.7 mmol/l. However, after a few weeks of cholesterol feeding resulting in plasma cholesterol levels of 2-5 mmol/l, the homologous graft accumulated cholesterol compared with intact aortic tissue in the rabbits and also compared with autologous aortic grafts. The intimal clearance of plasma cholesteryl ester, mainly high density lipoprotein cholesteryl ester, in the luminal layer of the aortic graft was 60-150 nl x cm-2 x hr-1 1-2 hours after transplantation. The intimal clearance in the corresponding intact thoracic aorta of the recipient animal was 5-20 nl x cm-2 x hr-1. The values were 1,500-3,000 nl x cm-2 x hr-1 51-298 days after transplantation, while the intimal clearance of the rabbit's own aorta remained unchanged. A pronounced increase in plasma lipoprotein permeability is thus an early event in transplanted arteries. It results in a higher cholesteryl ester influx that leads to cholesterol accumulation in the artery, but only if the rabbits are fed a cholesterol-enriched diet. This rabbit model may be useful in the search for interventional measures to prevent or diminish the accelerated coronary artery disease in transplanted hearts in humans. PMID- 1616903 TI - Determinants of plasma fibrinogen: relation to body weight, waist-to-hip ratio, smoking, alcohol, age, and sex. Results from the second MONICA Augsburg survey 1989-1990. AB - In the second World Health Organization MONItoring Trends and Determinants in CArdiovascular Disease (MONICA) Augsburg survey in 1989-1990 (n = 4,940), the association between nephelometric plasma fibrinogen level and lifestyle-related potential determinants was assessed in 4,434 subjects aged 25-74 years (89.8% of participants). Irrespective of pregnancy and the use of oral contraceptives, crude fibrinogen values were consistently higher in women than in men of all ages (age-standardized difference, 12.2 mg/dl; 95% confidence interval, 7.0-17.4 mg/dl). Fibrinogen concentrations were positively correlated (p less than or equal to 0.0001) with age, body mass index, and waist-to-hip ratio in both sexes and with cigarette smoking in men and were negatively correlated with alcohol consumption in both sexes. In multiple linear regression analyses using categorized determinants as independent variables, a strongly J-shaped relation for body mass index in women and a linear association for waist-to-hip ratio in men were revealed. Smoking had a dose-dependent effect on fibrinogen concentration in men but a lesser effect in women. For alcohol consumption a U shaped association was found, particularly in men. The curvilinear relations were confirmed in multiple polynomial regression models using continuous determinant variables. The potential epidemiological impact of a determinant was assessed by calculating differences in adjusted fibrinogen concentrations associated with the 10th and 90th percentile values of the determinant distributions actually observed among the study participants. This impact on the population fibrinogen level was most pronounced for age in both sexes, followed by body mass index, cigarette smoking, and alcohol consumption in women and by smoking, waist-to-hip ratio, and alcohol consumption in men.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616904 TI - Induction of arteriosclerosis in normocholesterolemic rabbits by immunization with heat shock protein 65. AB - Previous studies have established the presence of high numbers of activated T lymphocytes and "aberrant" expression of major histocompatibility complex class II antigens by endothelial and smooth muscle cells in human atherosclerotic lesions, implicating the involvement of a local cellular immune response. The identity of the antigen(s) eliciting this immune response, the extent of their effect, and the atherogenic stage at which they occur remain to be determined. In the present studies, 120 normocholesterolemic New Zealand White rabbits were immunized one or more times with various antigens, with or without adjuvants. The antigens and adjuvants included human or rabbit atherosclerotic lesion proteins, ovalbumin, Freund's complete and/or incomplete adjuvants, recombinant mycobacterial heat shock protein 65 (hsp65), and two hsp-free adjuvants, Ribi complete adjuvant and lipopeptide. In addition, some groups received a high cholesterol diet. Sixteen weeks after the first immunization the animals were killed, and arteriosclerotic lesions in the intima of the aortic arch were found to have developed only in those animals immunized with antigenic preparations containing hsp, either in the form of whole mycobacteria or as purified recombinant hsp65, although their serum cholesterol levels were normal. No arteriosclerotic changes exceeding those of controls were found in the other groups, irrespective of the antigen used. Immunohistopathologic examination revealed that the lesions contained 20% T cells, 10-30% macrophages, and 10-40% smooth muscle cells. Analysis of the peripheral blood T-lymphocyte proliferative responses revealed that the occurrence of lesions was positively correlated with the presence of hsp65-reactive T cells, suggesting that hsp65 is involved in the induction of arteriosclerotic lesions. Furthermore, combined immunization with hsp-containing material and a cholesterol-rich diet provoked development of significantly more severe atherosclerosis and the appearance of characteristic foam cells. We conclude that an (auto)immune response to hsp may initiate the development of atherosclerosis and that a high blood cholesterol level is only one albeit a very important risk factor. PMID- 1616905 TI - Mechanisms controlling competence gene expression in murine fibroblasts stimulated with minimally modified LDL. AB - Mildly oxidized low density lipoprotein (minimally modified low density lipoprotein [MM-LDL] is capable of inducing gene expression in cells of the artery wall. In this study, we investigated the mechanisms that control the mRNA expression of JE, KC, c-myc, and c-fos in quiescent mouse L-cell fibroblasts stimulated with MM-LDL. The data demonstrate that MM-LDL induces increases greater than or equal to 20-fold in the levels of transcripts of these genes within 15-60 minutes. Of the four genes examined, JE and KC mRNA showed the greatest response to MM-LDL. The pattern of induction by MM-LDL is distinct from that observed in fibroblasts stimulated with serum, a known inducer of these genes. Treatment with cycloheximide (10 micrograms/ml) did not block the MM-LDL induced increase in the mRNA levels of these genes. The increase of JE and KC mRNA levels in response to MM-LDL could be blocked by treatment with actinomycin D (5 micrograms/ml). In nuclear runoff studies, MM-LDL increased the transcription rate of JE and KC at 4 hours by 13-fold and fivefold, respectively. Small but reproducible stimulations of c-fos and c-myc transcription by MM-LDL were also observed. In addition, the half-life of JE mRNA was increased after addition of MM-LDL to fibroblasts, suggesting that the MM-LDL-induced accumulation of these mRNAs might be accomplished by both transcriptional and posttranscriptional mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616906 TI - Reduced HDL2 cholesterol subspecies and elevated postheparin hepatic lipase activity in older men with abdominal obesity and asymptomatic myocardial ischemia. AB - Silent myocardial ischemia (SI), an asymptomatic manifestation of coronary artery disease (CAD), was identified in 10% of apparently healthy nonsmoking, nondiabetic older (60 +/- 7 years, mean +/- SD) men with normal plasma cholesterol levels. We hypothesized that in the absence of other major risk factors for CAD, the men with SI would have reduced plasma levels of high density lipoprotein (HDL) and HDL2 subspecies due to an upper-body fat distribution (waist-to-hip ratio [WHR]), hyperinsulinemia, and abnormal postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities. Compared with 47 normal control subjects of similar age, obesity, and maximal aerobic capacity, the 18 men with SI had higher plasma triglyceride (TG) (162 +/- 71 versus 102 +/- 39 mg/dl, p less than 0.001) and lower HDL-C (33 +/- 6 versus 37 +/- 7 mg/dl, p less than 0.02) levels with no difference in low density lipoprotein cholesterol level. The HDL2b and HDL2a subspecies measured by gradient gel electrophoresis were also lower in the men with SI (p less than 0.01). The plasma glucose and insulin responses during an oral glucose tolerance test were the same in both groups. Postheparin plasma HL activity was significantly higher in 12 men with SI than in 41 control subjects (34 +/- 8 versus 27 +/- 10 mumol/ml.hr-1, p less than 0.03) and was correlated with log insulin area (r = 0.36, p less than 0.05) and WHR (r = 0.32, p less than 0.05) in the control subjects but not in the men with SI. In the control group, the percent HDL2b subspecies was correlated inversely with postheparin plasma HL activity (r = -0.46, p less than 0.01, n = 41) as well as WHR (r = -0.49, p less than 0.001, n = 47) and log insulin area (r = -0.37, p less than 0.05, n = 47) but not in the men with SI. Postheparin LPL activity was the same in both groups of men and did not correlate with HDL, WHR, insulin, or plasma TG levels. As the control subjects and men with SI had comparable degrees of abdominal obesity and hyperinsulinemia, these results suggest that the reduced HDL-C levels in men with SI may be related to elevations in HL activity. Thus, abdominal obesity, hyperinsulinemia, elevated TG levels, and low HDL-C and HDL2 subspecies levels may predispose these older men to atherosclerosis. PMID- 1616907 TI - Superoxide-dependent stimulation of leukocyte adhesion by oxidatively modified LDL in vivo. AB - Low density lipoprotein modified by oxidation (Ox-LDL) causes adhesion of leukocytes to the endothelium, a feature common in early atherogenesis. Because leukocyte adhesion under various pathophysiological conditions involves superoxide generation, we explored the possibility that superoxide is likewise involved in leukocyte adhesion in response to Ox-LDL. For our studies, we used the dorsal skin fold chamber model for intravital microscopic observation of leukocyte-endothelium interactions in hamsters. We show here that injection of human LDL (4 mg/kg LDL cholesterol oxidatively modified by incubation in 7.5 microM Cu2+ for 18 hours at 37 degrees C) elicited in control hamsters (n = 7) the rolling and adhesion of circulating leukocytes along the endothelium of arterioles and postcapillary venules. This adhesion was significantly attenuated when hamsters were pretreated with bovine copper-zinc-superoxide dismutase (CuZn SOD, 0.25 mg/kg, n = 7) or heparin (2,000 IU/kg, n = 7). The CuZn-SOD infusion and the heparin-induced release of extracellular SOD from endothelial cell surfaces to plasma resulted in nearly equal plasma SOD activities. Further inhibition of Ox-LDL-induced leukocyte adhesion could not be achieved by increasing the dose of CuZn-SOD to 5 mg/kg (n = 6). Pretreatment of the hamsters with inactivated CuZn-SOD showed no effect. These results indicate that Ox-LDL stimulates leukocyte adhesion through a superoxide-dependent step, and they indicate a possible mechanism by which antioxidants might inhibit the onset of experimental and clinical atherosclerosis. PMID- 1616908 TI - Effect of dietary olive and sunflower oils on the lipid composition of the aorta and platelets and on blood eicosanoids in rats. AB - The effects on aortic and platelet fatty acid compositions and on blood levels of prostacyclin and thromboxane A2 of low- and high-fat diets containing olive oil or sunflower oil were studied. For 4 weeks, four groups of weanling rats were fed a basal diet containing 5% or 25% olive oil or sunflower oil. Rats fed olive oil diets showed higher levels of 18:1(n-9) and polyunsaturated fatty acids of the n 3 series and lower percentages of 18:0 and 18:2(n-6) in aortic and platelet phosphatidylcholine and phosphatidylethanolamine than those fed the sunflower oil diets. Arachidonic acid increased in platelet phosphatidylethanolamine and aortic phosphatidylcholine of rats fed the diet containing 5% sunflower oil compared with those fed 5% olive oil. Plasma 6-ketoprostaglandin F1 alpha increased in both groups of animals fed olive oil while these rats also showed the lowest levels of serum thromboxane B2 and plasma cholesterol. Olive oil feeding leads to changes in lipid metabolism of the vascular compartment that could be favorable in the prevention of thrombosis and atherosclerosis. PMID- 1616909 TI - Vascular endothelial cell proteoglycans are susceptible to cleavage by neutrophils. AB - Heparan sulfate proteoglycan associated with vascular endothelial cells in vivo plays an important role in a number of endothelial functions, including the inhibition of intravascular coagulation and extravasation of plasma proteins and blood cells. In this report, we demonstrate that polymorphonuclear neutrophils, as well as cell-free neutrophil supernatants, lead to a rapid and dramatic loss of proteoglycan from endothelial cells in the absence of evidence of cell lysis. This cleavage appears to be relatively (although not absolutely) selective for heparan sulfate and is mediated by neutrophil-derived serine proteases. Inhibitors of neutrophil elastase appear to be the most effective inhibitors of proteoglycan release. Furthermore, purified human neutrophil elastase also leads to cleavage of cellular proteoglycans, although not to the same extent as neutrophils or neutrophil supernatants. Proteoglycans compared with all other protein-containing macromolecules appear to be especially vulnerable to neutrophil-mediated cleavage. The results of this study may be germane to the interaction of neutrophils with endothelium during the inflammatory process, during which the loss of endothelial heparan sulfate proteoglycan may play a critical role in the vascular injury that often accompanies inflammation. PMID- 1616910 TI - In vivo metabolism of apolipoprotein A-I in a patient with homozygous familial hypercholesterolemia. AB - Familial hypercholesterolemia (FH), caused by a defect in the low density lipoprotein (LDL) receptor, results in high plasma concentrations of LDL cholesterol due to both overproduction and delayed catabolism of LDL. FH is also associated with significantly lower levels of plasma high density lipoprotein cholesterol and apolipoprotein (apo) A-I in both heterozygous and homozygous patients. However, the metabolic basis of the hypoalphalipoproteinemia in FH has not been elucidated. We investigated the kinetics of apo A-I in a homozygous FH patient and two normal control subjects by using endogenous labeling with a stable isotopically labeled amino acid. Study subjects were administered a primed constant infusion of 13C6-phenylalanine for 12 hours. Apolipoproteins were isolated from plasma drawn at selected time points and analyzed for their isotopic enrichment by gas chromatography-mass spectrometry. The fractional catabolic rate of apo A-I in the FH subject was found to be substantially increased (0.38 day-1) compared with that of the normal subjects (mean, 0.26 day 1). In addition, the apo A-I production rate was decreased in the FH subject (6.5 mg/kg.day-1) compared with the normal subjects (mean, 11.1 mg/kg.day-1). In conclusion, the low levels of high density lipoprotein cholesterol and apo A-I in this homozygous FH patient are due to the combined metabolic defects of increased apo A-I catabolism and decreased apo A-I production. PMID- 1616912 TI - March 1991 meeting of the Israel Physiological and Pharmacological Society. Abstracts. PMID- 1616913 TI - April 1992 meeting of the Israel Physiological and Pharmacological Society. Abstracts. PMID- 1616911 TI - Transport of HDL cholesterol esters to the liver is not diminished by probucol treatment in rats. AB - This study examined the relation of decreased high density lipoprotein (HDL) levels in probucol-fed rats and the transport of HDL cholesterol esters (CEs) to the liver. HDLs from both control rats and rats fed 1% probucol for 3 weeks were doubly labeled in their CE and apolipoprotein A-I moieties with intracellularly trapped tracers and then intravenously injected into probucol-fed or control rats for determination of plasma decay kinetics and sites of tracer uptake. Results for HDL from control and probucol-fed rats were not different. The fractional catabolic rate (FCR) of plasma HDL CE was significantly increased by probucol feeding (23%) so that mass transport of HDL CE through the plasma compartment was not significantly different from that in control rats. The plasma FCR for apolipoprotein A-I did not change. Similarly, the FCR for uptake of HDL CE by the liver increased on probucol feeding (20%), resulting in a near-normal rate of HDL CE mass uptake, whereas the FCR for HDL particle uptake (measured by apolipoprotein A-I uptake) did not change. Thus, the maintenance of near-normal HDL CE uptake by the liver was exclusively due to increased selective uptake (32%). To the extent that hepatic uptake of HDL CE mediates reverse cholesterol transport, that process was not significantly compromised in rats fed 1% probucol. PMID- 1616914 TI - Biomembranes. PMID- 1616915 TI - Avidin-induced lysis of biotinylated erythrocytes by homologous complement via the alternative pathway depends on avidin's ability of multipoint binding with biotinylated membrane. AB - It was reported that avidin and streptavidin induce lysis of prebiotinylated red blood cells via the alternative pathway of both homologous and heterologous complement. Both of these proteins have four biotin-binding sites, providing a polyvalent interaction with biotinylated components of the erythrocyte membrane. We have compared the effects of mono- and multipoint avidin attachment on the sensitivity of biotinylated erythrocytes to lysis by the complement system. In the presence of anti-avidin antibody, avidin-bearing biotinylated erythrocytes were rapidly lysed by heterologous serum. This lysis was independent from the mode of avidin attachment, implying that complement activation by the classical pathway triggered by interaction between C1 and avidin-bound antibody on the erythrocyte surface is independent from the avidin's ability of polyvalent (multipoint) binding with biotinylated membrane components. In the absence of anti-avidin antibody, biotinylated erythrocytes bearing polyvalently attached avidin were lysed by homologous complement better than cells bearing avidin, which possesses reduced ability for multipoint binding with biotinylated erythrocyte. Two independent approaches to reduce avidin's ability of multipoint binding were used: decrease in surface density of biotin on the erythrocyte membrane and blockage of biotin-binding sites of avidin. Both methods result in reduced lysis of avidin-bearing erythrocytes as compared with erythrocytes bearing an equal amount of polyvalent-bound avidin. Thus the activation of homologous complement via the alternative pathway depends on avidin's ability to 'cross-link' to the biotinylated components of the erythrocyte membrane. PMID- 1616916 TI - NADH-activated cell-free transfer between Golgi apparatus and plasma membranes of rat liver. AB - This report concerns development of a cell-free system from rat liver to study transport of membrane constituents from the Golgi apparatus to the plasma membrane. Highly purified Golgi apparatus as donor and a mixture of sheets and vesicles as plasma membrane acceptor fractions were combined to analyze requirements for lipid and protein transport. In the reconstituted system, the Golgi apparatus donor was in suspension. To measure transfer, membrane constituents of the donor membranes were radiolabeled with [3H]acetate (lipids) or [3H]leucine (proteins). The plasma membrane vesicles were used as the acceptor and were unlabeled and immobilized on nitrocellulose for ease of recovery and analysis. The reconstituted cell-free transfer was dependent on temperature, but even at 37 degrees C, the amount of transfer did not increase with added ATP, was not specific for any particular membrane fraction or subfraction nor was it facilitated by cytosol. ATP was without effect both in the presence or absence of a cytosolic fraction capable of the support of cell-free transfer in other systems. In contrast to results with ATP, NADH added to the reconstituted system resulted in an increased amount of transfer. A further increase in transfer was obtained with NADH plus a mixture of ascorbate and dehydroascorbate to generate ascorbate free radical. The transfer of labeled membrane constituents from the Golgi apparatus to the plasma membrane supported by NADH plus ascorbate radical was stimulated by a cytosol fraction enriched in less than 10 kDa components. This was without effect in the absence of NADH/ascorbate radical or with ATP as the energy source. Specific transfer was inhibited by both N-ethylmaleimide and GTP gamma S. The findings point to the possibility of redox activities associated with the trans region of the Golgi apparatus as potentially involved in the transport of membrane vesicles from the Golgi apparatus to the cytoplasmic surface of the plasma membrane. PMID- 1616917 TI - Vanadium-induced Cl(-)-secretion in rabbit descending colon is mediated by prostaglandins. AB - Vanadium in the 4+ (vanadyl-ion) and 5+ (vanadate-ion) oxidation state stimulates furosemide-sensitive electrogenic Cl- secretion in isolated epithelia of rabbit descending colon. This effect is associated with an increased release of prostaglandin E2 from the tissue. Inhibitors of phospholipase A2 or cyclooxygenase abolish both vanadium-induced release of prostaglandin E2 and Cl- secretion. Neuronal mechanisms are not likely to be involved, as tetrodotoxin does not affect the vanadate induced Cl- secretion. Although vanadate is known to inhibit Na+,K(+)-ATPase activity, no inhibition of active Na+ transport was observed in intact colonic epithelia suggesting a rapid intracellular reduction of vanadate ions to vanadyl ions which have no inhibitory effect on the Na+,K(+) ATPase. The present findings therefore indicate that vanadate stimulated colonic Cl- secretion involves intracellular conversion of vanadate to vanadyl and release of prostaglandin E2. PMID- 1616918 TI - Lipid-drug interaction: a structural analysis of pindolol effects on model membranes. AB - The ternary system constituted by distearoylphosphatidylcholine, pindolol (a vasodilator drug) and water has been investigated by using X-ray diffraction and calorimetric techniques. The structural modifications induced by the drug have been determined and a possible interaction model has been derived. In particular, the pindolol content-temperature dependent phase diagram shows the occurrence of two new phases: the first is an interdigitated gel, and the second is a lamellar structure presenting an unusual mixed disordered-ordered conformation of the hydrocarbon chains (L alpha beta). The comparative analysis of electron density profiles relative to the L alpha beta phase, reveals significant modifications in the paraffinic region of the lipid layer. In agreement with thermodynamic results, the structural data suggest that the drug induces a stiffening and a tightening of the hydrocarbon chains. Moreover, the hydrophilic properties of the membrane (particularly in P beta, and L alpha beta phases) present an evident dependence with the drug concentration. PMID- 1616920 TI - Efflux of potassium (86Rb+) attenuates the volume-restorative effect of sodium amino acid cotransport in rat renal inner medullary cells shrunken by exposure to hyperosmotic media. AB - When the osmolality of the bathing medium was increased from 710 to 2000 mosmol/kg H2O, cells in incubated slices of rat renal inner medulla lost water and K+, and the rate of efflux of preloaded 86Rb+ (a tracer for K+) was significantly depressed. Addition of 2-aminoisobutyric acid (AIB, 10 mmol/l) partly restored cell water content but without re-accumulation of K+; the rate of 86Rb+ efflux was greatly increased. The presence of Ba2+ (1 mmol/l) or trifluoperazine (50 mumol/l) led to complete recovery of cell volume and K+ contents, with markedly reduced efflux of 86Rb+. Neither additive had any significant effect upon these variables in the absence of AIB or in media of 710 mosmol/kg. Efflux of 86Rb+ was pH-sensitive within the physiological range, and was depressed when external AIB was reduced below approx. 5 mmol/l. When external Na+ was increased from 145 to 500 mmol/l (total osmolality 350 to 2500 mosmol/kg) efflux was retarded only slightly if AIB was present, but markedly if AIB was omitted. Inner medullary cells may contain a class of Ba(2+)-inhibitable, calmodulin-dependent K+ conductive pathway which is activated in strongly hyperosmotic media by the operation of an inwardly-directed Na(+)-amino acid symport (cf. Law, R.O. (1988) Pflugers Arch. 413, 43-50) and which serves to moderate the volume-restorative effect of this membrane mechanism. PMID- 1616919 TI - The Na(+)-Ca2+ exchanger activity in cerebrocortical nerve endings is reduced in old compared to young and mature rats when it operates as a Ca2+ influx or efflux pathway. AB - The activity of the Na(+)-Ca2+ exchanger, which regulates the entry and the extrusion of Ca2+ ions from nerve endings was investigated in Percoll-purified cerebrocortical synaptosomes of aged rats. 45Ca2+ uptake in a Na(+)-free medium and 45Ca2+ efflux in a 145 mM Na+ medium were significantly reduced in cerebrocortical synaptosomes from aged rats (24 months) as compared to those occurring in young (4 months) and mature (14 months) rats. 45Ca2+ influx induced by 55 mM K+, a concentration of K+ ions which selectively promotes Ca2+ entry through voltage-sensitive Ca2+ channels (VSCC), was significantly reduced in mature and aged rats as compared to that occurring in young rats. The impairment of these mechanisms in aged rats is not accompanied by any variation of fura-2 monitored Ca2+ levels under resting and depolarizing conditions. PMID- 1616921 TI - Exocytosis upon osmotic swelling in human epithelial cells. AB - Upon osmotic swelling human epithelial cells exhibited significant increases in the membrane capacitance. Evidence for exocytosis includes its dependency on temperature, cytosolic Ca2+ and ATP as well as its sensitivity to guanosine 5'-O (3-thio)triphosphate (GTP gamma S) and N-ethylmaleimide (NEM). A role of the osmotic exocytosis in the subsequent cell volume regulation is suggested. PMID- 1616922 TI - Behaviour of a glycosphingolipid with unsaturated fatty acid in phosphatidylcholine bilayers. AB - N-(Oleoyl)galactosylceramide with perdeuterated acyl chain was prepared by partial synthesis, and studied by wide line 2H-NMR in phospholipid liposomes. Spectra were obtained for low glycolipid concentrations in bilayers of dimyristoyl-, distearoyl-, and 1-palmitoyl-2-oleoylphosphatidylcholines. In an attempt to isolate the effects of glycosphingolipid fatty acid cis unsaturation on glycolipid behaviour in membranes, spectral findings related to the above species were compared to literature NMR data for pure 1-palmitoyl-2 oleoylphosphatidylcholine bilayers in which the oleoyl chain of the phospholipid had been deuterated, and to analogously deuterated glycerol based lipids in Acholeplasma laidlawii membranes. The results for N-(oleoyl d33)galactosylceramide proved to be qualitatively and quantitatively very similar to published data dealing with glycerol based lipids at comparable temperatures. In addition, the results were strikingly similar for glycolipids dispersed in saturated and unsaturated phospholipid host matrices. It would appear that the primary effects of cis 9,10 fatty acid unsaturation in glycosphingolipids (at low concentration in fluid phospholipid membranes) are the same as those of fatty acid cis unsaturation in glycerolipids. It further appears that the overall dynamic behaviour of N-(oleoyl)galactosylceramide in fluid phospholipid membranes is very similar to that of glycerolipids with comparable acyl chains. PMID- 1616923 TI - Isoprenoid modification of proteins distinct from membrane acyl proteins in the prokaryote Acholeplasma laidlawii. AB - Isoprenylation is an important posttranslational modification that affects the activity, subunit interactions and membrane anchoring of different eukaryotic proteins. The small, cell-wall-less prokaryote Acholeplasma laidlawii has more than 20 membrane acyl-proteins enriched in myristoyl and palmitoyl chains. Radioactive mevalonate, a precursor to isoprenoids, was incorporated into several specific membrane proteins of 20 to 45 kDa and two soluble proteins of 23-25 kDa, respectively. No acyl proteins and none of the polar acyl lipids became labelled but these are all labelled by radioactive fatty acids. Mevalonate was incorporated mainly into a minor neutral, non-saponifiable lipid which migrated just above a C30-isoprenoid (squalene) on TLC-plates. The isoprenoid chains could not be released by mild alkaline hydrolysis from most of the isoprenylated proteins, although this procedure releases acyl chains from lipids and all acylated proteins. Isoprenylated proteins were enriched in the detergent phase upon partition with the non-ionic detergent Triton X-114. This behaviour is similar to the acyl proteins of this organism and indicates that the isoprenoid chains give the proteins a hydrophobic character. PMID- 1616924 TI - Effects of lung surfactant proteolipid SP-C on the organization of model membrane lipids: a fluorescence study. AB - Lipid-protein interactions of pulmonary surfactant-associated protein SP-C in model DPPC/DPPG and DPPC/DPPG/eggPC vesicles were studied using steady-state and time-resolved fluorescence measurements of two fluorescent phospholipid probes, NBD-PC and NBD-PG. These fluorescent probes were utilized to determine SP-C induced lipid perturbations near the bilayer surface, and to investigate possible lipid headgroup-specific interactions of SP-C. The presence of SP-C in DPPC/DPPG membrane vesicles resulted in (1) a dramatic increase in steady-state anisotropy of NBD-PC and NBD-PG at gel phase temperatures, (2) a broadening of the gel-fluid phase transition, (3) a decrease in self-quenching of NBD-PC and NBD-PG probes, and (4) a slight increase in steady-state anisotropy of NBD-PG at fluid phase temperatures. Time-resolved measurements, as well as steady-state intensity measurements indicate that incorporation of SP-C into DPPC/DPPG or DPPC/DPPG/eggPC vesicles results in a increase in the fraction of the long lifetime species of NBD-PC. The results presented here indicate that SP-C orders the membrane bilayer surface, disrupts acyl chain packing, and may increase the lateral pressure within the bilayer. PMID- 1616925 TI - Lateral conductance parallel to membrane surfaces: effects of anesthetics and electrolytes at pre-transition. AB - The effects of dilute salts and anesthetics were studied on the impedance dispersion in the dipalmitoylphosphatidylcholine (DPPC) liposomes. Below the pre transition temperature, the apparent activation energy for conductance in DPPC H2O without salts was equivalent to pure water, 18.2 kJ mol-1. This suggests that the mobile ions (H3O+ and OH-) interact negligibly with the lipid surface below the pre-transition temperature. At pre-transition temperature, the apparent activation energy of the conductance decreased by the increase in the DPPC concentrations. The effects of various salts (LiCl, NaCl, KCl, KBr, and KI) on the apparent activation energy of the conductance were studied. Changes in anions, but not in cations, affected the activation energy. The order of the effect was Cl- less than Br- less than I-. Cations appear to be highly immobilized by hydrogen bonding to the phosphate moiety of DPPC. The smaller the ionic radius, the more ions are fixed on the surface at the expense of the free moving species. The apparent activation energy of the transfer of ions at the vesicle surface was estimated from the temperature-dependence of the dielectric constant, and was 61.0 kJ mol-1 in the absence of electrolytes. In the presence of electrolytes, the order of the activation energy was F- greater than Cl- greater than Br- greater than I-. When the ionic radius is smaller, these anions interact with the hydration layer at the vesicle surface and the ionic transfer may become sluggish. In the absence of electrolytes, the apparent activation energy of the dielectric constant decreased by the increase in halothane concentrations. In the presence of electrolytes, however, the addition of halothane increased the apparent activation energy. We propose that the adsorption of halothane on the vesicle surface produces two effects: (1) destruction of the hydration shell, and (2) increase in the binding of electrolytes to the vesicle surface. In the absence of electrolytes, the first effect predominates and the apparent activation energy is decreased. In the presence of electrolytes, the latter effect predominates and the apparent activation energy is increased. PMID- 1616926 TI - Effects of alkyl glycosides incorporated into liposomes prepared from synthetic amphiphiles on their tissue distribution in Ehrlich solid tumor-bearing mice. AB - A study of the effects of alkyl glycosides incorporated into synthetic liposomes with respect to their stability, their in vivo distribution in Ehrlich solid tumor-bearing mice and their in vitro interaction with liver cells was undertaken. The synthetic liposomes were prepared from N,N-didodecyl-N alpha-[6 (trimethylammonio)hexanoyl]-L-alaninamide bromide (N+C5Ala2C12) and labeled with 99mTc. n-Dodecyl glucoside (DG) and n-dodecyl sucrose (DS) were used as alkyl glycosides. The stability was hardly changed by incorporation of alkyl glycosides into the liposomes in saline and serum. The uptake of DG- and DS-modified N+C5Ala2C12 liposomes decreased in liver and spleen compared with that of unmodified N+C5Ala2C12 liposomes, resulting in an increase in blood and other tissues such as tumor, duodenum and kidney, where the DS-modified N+C5Ala2C12 liposomes had a marked tendency. It was observed with electron micrographs that the size of N+C5Ala2C12 liposomes became small by incorporation of alkyl glycoside. The smaller N+C5Ala2C12 liposomes were found to result in the lower uptake in liver. The interaction of the liposomes with liver cells in vitro indicated that both DG- and DS-modified liposomes had a low affinity for liver cells compared with the unmodified liposomes and the extent of interaction of the DS-modified liposomes was weaker than that of the DG-modified liposomes. PMID- 1616927 TI - Ontogeny of proximal colon basolateral membrane lipid composition and fluidity in the rabbit. AB - Basolateral membranes from rabbit proximal colon were prepared from isolated colonocytes throughout postnatal maturation, using a modification of published techniques. In suckling (14-20 day) and post-weaning/mature (35-49 day) animals, membranes were purified approx. 10-fold, based upon the enrichment of ouabain sensitive, sodium-potassium dependent adenosine triphosphatase activity. Membrane lipid analyses demonstrated age-dependent increases in total cholesterol and the cholesterol/phospholipid molar ratio, as well as decreases in phosphatidylethanolamine content and the fatty acid unsaturation index. Fluidity of basolateral membranes and membrane liposomes, determined from fluorescence anisotropy measurements using the lipid probes 1,6-diphenyl-1,3,5-hexatriene and DL-12-(9-anthroyl)stearic acid, demonstrated significant, ontogenic decreases in fluidity; and, additional studies showed that fluidity changes occurred early in the weaning period (by day 24 postnatally). Arrhenius plots of liposome anisotropies suggested a bilayer lipid thermotropic transition temperature of 22 degrees C in sucklings 26 degrees C in mature rabbits. These findings demonstrate that ontogeny of colonic basolateral membranes is associated with significant modulations in lipid composition and fluidity. PMID- 1616928 TI - Low-temperature phase behaviour of the major plant leaf lipid monogalactosyldiacylglycerol. AB - Heating and cooling thermograms of unsaturated MGDG samples isolated from the leaves of Vicia faba are surprisingly featureless. This reflects the low enthalpies associated with phase transitions in highly unsaturated lipids and the fact that these transitions, in the case of MGDG, are to a large extent masked by those associated with the freezing and melting of ice. Careful choice of thermal heating/cooling regimes, combined with the use of real-time X-ray diffraction and freeze-fracture measurements, permits a detailed analysis of the phase behaviour of the system. The phase behaviour of unsaturated MGDG samples is shown to be basically similar to that seen in saturated MGDG samples. The lipid which exists in the inverted hexagonal (HexII) liquid crystal phase at room temperature forms a highly disordered lamellar gel (L beta) phase on cooling to temperatures below about -15 degrees C. On reheating, this first reorganizes at a temperature of about -10 degrees C to form a well-defined Lc1 phase. Above about -2 degrees C, this melts to re-form the HexII phase. Samples re-cooled from temperatures between -2 degrees C and 14 degrees C revert directly to the Lc1 phase while samples cooled from higher temperatures form the L beta phase. This reflects the fact that the former samples contain small amounts of unmelted Lc1 phase lipid. The implications of these observations are discussed in terms of the general problems associated with the measurement of low-temperature phase behaviour of membrane lipids. PMID- 1616929 TI - Modelling of interaction of basic lipophilic ligands with cytochrome P-450 reconstituted in liposomes. Determination of membrane partition coefficients of S (-)-nicotine and N,N-diethylaniline from spectral binding studies and fluorescence quenching. AB - The spectral interaction of N,N-diethylaniline and S-(-)-nicotine with cytochrome P450IIB4 reconstituted into large unilamellar vesicles could properly be described by a model for interaction of basic lipid-soluble ligands with membrane bound acceptor sites in which linear partitioning of non-ionized ligand in the membrane is postulated. Apparent spectral dissociation constants Ksapp for type I binding of N,N-diethylaniline and for type II binding of S-(-)-nicotine increased linearly with increasing lipid volume fraction alpha L of the proteoliposomes. From plots of Ksapp vs. alpha L, the membrane partition coefficient of each ligand was calculated. The apparent affinity of cytochrome P450IIB4 for the ligands increased as the pH was raised from 6.0 to 8.5. However, effective dissociation constants were virtually independent of the pH, indicating that only the uncharged form of the basic ligands interact with cytochrome P450IIB4. For each compound, the apparent quenching rate constants kqapp derived from the Stern Volmer plots for dynamic quenching of the fluorescence intensity of 8-(2 anthryl)octanoic acid in liposomes, decreased with increasing liposomal concentration. Plots of (kqapp)-1 vs. alpha L of the liposomes yielded the overall bimolecular quenching rate constant kq of each quencher. The kq value for S-(-)-nicotine was about three orders of magnitude less than that for N,N diethylaniline. The values of the partition coefficient of N,N-diethylaniline, obtained from the binding studies and the fluorescence quenching measurements, were identical (on average, Kp amounted to 383). Analysis of the quenching data of N,N-diethylaniline with Scatchard plots likewise revealed that the association of the compound with liposomal membranes is a pure partition process. PMID- 1616930 TI - Effects of melatonin and light on porphyrin synthesis in the bovine retina, pigment epithelium and choroid. AB - The quantity of porphyrin synthesized in the presence of 10(-3) M delta aminolevulinic acid (ALA) is several times higher in the bovine pigment epithelium than in the retina. Synthesis in the retina was found to be increased by illumination, whereas synthesis in the pigment epithelium was decreased if the whole anatomical unit (retina-pigment epithelium-choroid) was cultivated together. The quantity of porphyrin synthesized in the presence of 10(-3) M ALA or 10(-6) M melatonin was different when the pigment epithelium and retina were separated. The combination 10(-3) M ALA with 10(-6) M melatonin inhibited retinal porphyrin synthesis after green light adaptation, while in the pigment epithelium green light adaptation induced porphyrin synthesis. It is postulated that the light-sensitive porphyrin-haeme synthesis of the retina-pigment epithelium choroid functional unit may serve and modulate the synthesis of guanylate cyclase for cGMP. PMID- 1616932 TI - Uptake of 67Cu by isolated human trophoblast cells. AB - The isolated human trophoblast was used as a system to analyze the effects of different physiological ligands on cellular uptake of copper. The results show that the uptake of copper by these cells follows a similar pattern for the ligands tested (histidine, albumin and ceruloplasmin) as that for copper chloride. The process follows a typical hyperbolic curve at 37 degrees C. The initial phase of uptake follows a linear pattern during 30 min at 37 degrees C and at least 60 min at 4 degrees C from which the uptake rate is calculated. However, a significant decrease in the uptake rate is observed for albumin. The effect of histidine on stimulating copper transport is observed in the presence of serum, a phenomenon which is considered to be due to the release of copper that is bound to albumin. These results support the role of ceruloplasmin as a copper transport protein which releases copper at the cell surface, and a subsequent transport of the released copper in a manner similar to that of copper chloride or copper-histidine complexes. PMID- 1616931 TI - Down-regulation of cellular proto-oncogenes during inhibition of rat parotid acinar cell proliferation. AB - The role of cell surface galactosyltransferase in mediating isoproterenol-induced parotid gland hypertrophy and hyperplasia was examined in rat parotid gland acinar cells. Introduction of the transferase modifier, alpha-lactalbumin, or galactosyltransferase-associated kinase inhibitor trifluoperazine, into beta agonist-treated rats prevented acinar cell proliferation as determined by [3H]thymidine incorporation after 96 h of treatment. However, [3H]thymidine incorporation into DNA after 24 h of treatment, with injection of a combination of isoproterenol/alpha-lactalbumin or isoproterenol/trifluoperazine, was similar to injections of isoproterenol alone; suggesting that acinar cells could be stimulated to undergo a single round of DNA synthesis. Northern blot analysis of myc and fos expression followed a similar pattern of down-regulation to control levels after 96 h but not after 24 h. Hybridization with erb B showed little change with proliferation, confirming previous observations on protein levels of the EGF-receptor in acinar cells. Western blot analysis of nuclear protein expression of myc revealed that isoproterenol caused an increase in a 62-kDa protein which was again down-regulated with inhibition of cell proliferation. Analysis of protein levels of Rb110 protein showed no change in protein level in the nucleus with cell proliferation, but did show an associated increase in protein phosphorylation in response to growth stimulation. PMID- 1616934 TI - Investigation of a role for reduction in ferric iron uptake by mouse duodenum. AB - 59Fe uptake rates by mouse duodenal fragments incubated in vitro were markedly reduced by non-permeable reagents, ferricyanide (oxidising agent) and ferrozine (Fe2+ chelator), in the medium; ferrocyanide had no effect. Reduction of Fe3+, as reflected by an increase in ferrozine-(Fe2+)-chelatable iron, was observed in the presence of the tissue fragments. The generation of Fe2+ occurred linearly with time, was independent of the medium ferrozine concentration, and was not due to release of reducing factors from the duodenal fragments. Fe(3+)-reducing activity was mainly present on the mucosal surface and was localised primarily to the proximal region of the small intestine. Changes in Fe3+ reduction rates closely parallelled the changes in duodenal 59Fe uptake, when metabolic inhibitors or modulators of membrane potential were included in the medium. The enhancement in duodenal mucosal 59Fe uptake in chronic hypoxic and iron-deficient mice parallelled the changes in the tissue reduction of medium Fe3+. Moreover, the rates of reduction were quantitatively similar to rates of uptake. These observations indicate that a sequential reduction and uptake process operates for Fe3+ uptake in mouse duodenum. PMID- 1616933 TI - Endothelial cell-conditioned medium modulates the synthesis and structure of proteoglycans in vascular smooth muscle cells. AB - We studied the effect of bovine endothelial cell-conditioned medium on proteoglycan synthesis by bovine aorta smooth muscle cells. Confluent cultures were incubated with [35S]sulfate, [3H]glucosamine or [3H]serine in medium alone (control), or medium that had been conditioned on confluent endothelial cells. Metabolically labelled proteoglycans secreted into the culture medium and associated with the cell layer were quantified. During a 24 h incubation, endothelial cell-conditioned medium increased [35S]sulfate and [3H]glucosamine incorporation into medium and cell-layer proteoglycans by 59% and 95%, respectively, above controls. [3H]Serine incorporation into proteoglycan core protein was increased by 150%. The effect of endothelial cell-conditioned medium on [35S]sulfate incorporation was concentration dependent. The stimulatory effects of the conditioned medium were abolished by cycloheximide and actinomycin D, inhibitors of protein synthesis and transcription, respectively. Endothelial cell-conditioned medium caused no significant change in the degradation or secretion of proteoglycans, indicating that the increase in proteoglycans was due to increased de novo synthesis. TGF-beta neutralizing antibody inhibited 22% of the stimulatory effect of the conditioned medium, suggesting that part of the stimulation was mediated by TGF-beta. Ion-exchange chromatography of [35S]proteoglycans in the culture medium of smooth muscle cells yielded two major peaks at 0.52 and 0.57 M NaCl in both control and experimental cultures. In both cases the second peak, which represented approx. 80% of the total radioactivity, contained isomeric chondroitin sulfate proteoglycan with chondroitin sulfate and dermatan sulfate accounting for 90% and 10% of the isomers, respectively. The isomeric chondroitin sulfate proteoglycan was fractionated by hydrodynamic size on Sepharose CL-4B, resulting in three fractions (A, B and C). Analytical column chromatography of fractions A and B on Sepharose CL-2B demonstrated that proteoglycans from cultures incubated with endothelial cell-conditioned medium were larger in size than those from control cultures (M(r) fraction A, 1700,000, compared with 1200,000 M(r); fraction B, 540,000, compared with 390,000). The molecular weights of the core proteins were unchanged. The larger size of proteoglycan A in cultures exposed to endothelial cell-conditioned medium was due to an increase in both the glycosaminoglycan chain number (29 compared to 25) and molecular mass (M(r) 52,000, compared to 40,000). The hydrodynamic size of the glycosaminoglycans in proteoglycan B of control and experimental cultures was identical (M(r) 40,000). Therefore, the increase in the molecular mass of this proteoglycan was attributable to an increase in glycosaminoglycan chain number (12 compared to 9).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1616935 TI - The unpolymerized form of tubulin is the target for microtubule inhibition by photoactivated tetra(4-sulfonatophenyl)porphine. AB - Several porphyrins, including tetra(4-sulfonatophenyl)porphine, sensitize cells to photoinactivation. The treatment leads to an accumulation of cells in mitosis, directly or indirectly due to a perturbation of the mitotic spindle. The present work relates to the target for this mode of action. Cells incubated with tetra(4 sulfonatophenyl)porphine were exposed to light and the microtubules were quantified 30 min after light exposure. The amount of microtubules decreased with increasing fluences. The reduction in the amount of microtubules after light exposure was enhanced by prior treatment with nocodazole (1 microgram/ml for 20 min) or low temperature (1 degree C for 60 min). When nocodazole was combined with the photochemical treatment the extent of the inhibition of microtubule formation was dose-dependent only for the lowest fluences applied. Additional light exposure did not further reduce the amount of microtubules 30 min after light exposure. The results presented indicate that the unpolymerized fraction of tubulin is the target for photochemical inhibition of microtubule formation. PMID- 1616936 TI - A low-spin iron complex in human melanoma and rat hepatoma cells and a high-spin iron(II) complex in rat hepatoma cells. AB - Human melanoma and rat hepatoma cells cultured in the presence of low concentrations (2.5 microM) of low-molecular-weight iron (Fe) chelates and Fe transferrin complexes have been studied with 57Fe Mossbauer spectroscopy. The spectra show that holoferritin is only a minor fraction of the total iron present in the cells. The major form of Fe was in a low-spin state unlike the high-spin Fe(III) found in ferritin. Only about 10% of the Fe could be attributed to ferritin. In addition, the hepatoma cells had a high-spin Fe(II) spectral component which made up about 20% of the Fe present. PMID- 1616937 TI - Accumulation of S-D-lactoylglutathione and transient decrease of glutathione level caused by methylglyoxal load in isolated hepatocytes. AB - Methylglyoxal is converted to D-lactic acid through a conjugation with glutathione and S-D-lactoylglutathione is an intermediate of this pathway. In isolated hepatocytes prepared from fed mice incubated without nutrients (glucose, pyruvate and amino acids) the formation and release of S-D-lactoylglutathione and also a continuous lowering of cellular glutathione were demonstrated upon addition of methylglyoxal (20 mM). Under these incubation conditions, the glutathione content of the cells decreased in the controls. On the other hand, in hepatocytes incubated in a medium supplemented with the above-mentioned compounds an accumulation of S-D-lactoylglutathione and a transient decrease of glutathione were shown after addition of methylglyoxal. Under these experimental circumstances the glutathione content of the cells was preserved. Buthionine sulfoximine--an inhibitor of glutathione synthesis--prevented the restoration of glutathione level in hepatocytes observed in the presence of methylglyoxal; emetine--an inhibitor of protein synthesis--was ineffective. It is suggested that increased methylglyoxal formation may have a role in alterations of glutathione metabolism under conditions when serum acetone is increased and methylglyoxal production from acetone is elevated. PMID- 1616938 TI - Binding of endotoxin to macrophages; interactions of spin-labelled saccharide residues. AB - The molecular mechanisms of endotoxin action are poorly understood. A prerequisite to cellular activation by this agent must be interaction (binding) with the plasma membrane. In this study we have investigated the role of the polysaccharide region of endotoxin (LPS) in binding to macrophages and macrophage like cell lines. The LPS molecules, from Escherichia coli O111.B4, J5 and the lipid-A, were spin labelled with 2,2,6,6-tetramethylpiperidine-N-oxyl] (Tempo) free radical in their sugar residues, and examined by electron spin resonance spectroscopy. This is the first report of the synthesis of spin-labelled endotoxins. Measurement of the rotational correlation times (Tc) indicated that the saccharide resides do not bind to membrane surface structures and suggests that the binding of LPS to macrophages is mediated by the lipid acyl chains. Anti sera to LPS from E. coli O111.B4 was effective in binding to the polysaccharide of the same LPS bound to the cell surface. PMID- 1616939 TI - Changes in catalase activity and concentration during ovarian development and differentiation. AB - The ovaries of immature rats were used to prepare a peroxisome-enriched fraction by differential centrifugation. Following gonadotropin stimulation, which caused large numbers of follicles to develop into corpora lutea, the specific activity of catalase in the peroxisome-enriched fraction increased 5-fold, while catalase recovered in the post-30,000 x g supernatant did not increase in activity. The increase in catalase specific activity in the peroxisome enriched fraction was shown to be due to an increased concentration of the enzyme as determined by Western blotting. Catalase in pig granulosa cells also increased in specific activity as the follicles aged and luteinized. This increase appeared to parallel increases in the concentration of cytochrome P-450scc. We conclude there is a differential regulation of the peroxisomal and cytosolic pools of rat ovarian catalase. PMID- 1616940 TI - Inhibition of phospholipase A2 and insulin secretion in pancreatic islets. AB - Arachidonic acid may be an important mediator of insulin secretion since (1) glucose activates phospholipase A2 thus increasing endogenous unesterified levels of arachidonic acid, (2) arachidonic acid mobilizes Ca2+ from the islet endoplasmic reticulum and (3) arachidonic acid has been proposed to regulate voltage-dependent Ca2+ channels in the beta-cell. We have used the phospholipase A2 inhibitor, (p-amylcinnamoyl)anthranilic acid (ACA), to determine whether phospholipase A2 activation is required for glucose-induced insulin secretion. ACA inhibited in a dose-dependent manner glucose-induced insulin secretion, as well as glyceraldehyde and alpha-ketoisocaproic acid-induced insulin secretion. ACA also totally abolished glucose-induced arachidonate accumulation but did not affect phospholipase C suggesting that it was specific for phospholipase A2. Furthermore, ACA did not inhibit glucose oxidation. These observations suggest that glucose-induced arachidonate increase is essential for insulin secretion. PMID- 1616941 TI - Modulation by protein kinase C of the hormonal responsiveness of hepatocytes from lean (Fa/fa?) and obese (fa/fa) Zucker rats. AB - The effect of phorbol myristate acetate (PMA) on the hormonal responsiveness of hepatocytes from lean and obese Zucker rats was studied. Phenylephrine-stimulated phosphatydylinositol labeling and phosphorylase activation were antagonized by PMA in cells from obese and lean animals; bigger residual effects were observed in cells from obese animals even at high PMA concentrations. Cyclic AMP accumulation induced by isoproterenol, glucagon, forskolin and cholera toxin was higher in cells from lean animals than in those from obese rats. PMA diminished glucagon- and cholera toxin-induced cyclic AMP accumulation; cells from lean animals were more sensitive to PMA. Two groups of isoforms of protein kinase C (PKC) were observed in hepatocytes from Zucker rats using DEAE-cellulose column chromatography: PKC 1 and PKC 2. The PKC 1 isozymes were separated into four peaks using hydroxylapatite: aa, 1a (PKC-beta), 1b (PKC-alpha) and 1c. Short treatment with PMA decreased the activity of PKC 1 (peaks 1b (PKC-alpha) and 1c) and to a lesser extent of PKC 2; cells from lean animals were more sensitive to PMA than those obtained from obese rats. Our results indicate that cells from genetically obese Zucker rats are in general less sensitive to this activator of protein kinase C than those from their lean littermates. The possibility that alterations in the phosphorylation/dephosphorylation cycles, that control metabolism and hormonal responsiveness, may contribute to this obese state is suggested. PMID- 1616942 TI - Receptor binding on whole cells can oscillate. AB - The study of the kinetics of binding of the opiate receptor agonist [3H]DADLE with NG108-15 cell suspensions has revealed a new periodic biological phenomenon, i.e., oscillations of the cellular receptor activity. The absence of oscillations for binding of the receptor antagonist shows that oscillations occur as a result of the transformation of the receptor signal only. PMID- 1616943 TI - Cytosolic calcium oscillations induced by hepatocyte growth factor (HGF) in single fura-2-loaded cultured hepatocytes: effects of extracellular calcium and protein kinase C. AB - Hepatocyte growth factor (HGF) induced the periodic fluctuations of cytosolic calcium concentration ([Ca2+]i) in primary cultured rat hepatocytes, which were dependent on extracellular calcium. The HGF-induced [Ca2+]i oscillations were suppressed by the pretreatment with phorbol 12-myristate 13-acetate (PMA). Administration of PMA during oscillations also caused their blockade, but the subsequent addition of protein kinase C (PKC) inhibitor H-7 reversed the inhibitory effects of PMA, thereby resulting in the resumption of the oscillatory responses. Moreover, the prior exposure to H-7 caused apparent increases in [Ca2+]i spike peaks elicited by HGF. These results suggest a negative modulation via PKC in HGF-induced repetitive [Ca2+]i transients. The absence of HGF-induced oscillations after the thapsigargin treatment indicates that the agonist sensitive intracellular Ca2+ pool plays a crucial role in the [Ca2+] oscillations. PMID- 1616944 TI - New synthesis of immunogenic N6-isopent-2-enyladenosine-protein conjugate. Preparation, purification, and specificity of related antibodies. AB - An original procedure which preserves the structure of the sugar ring is described to link a plant hormone as N6-isopent-2-enyladenosine [( 9R]iP) onto a protein carrier to prepare a more specific immunogen. This cytokinin is bound to bovine serum albumin (BSA) and ovalbumin by a five-step procedure. These [9R]iP protein conjugates have a maximal absorption at 269 nm and show molar ratios of hormone bound to proteins in the range of 12:1 and 18:1 for BSA and ovalbumin, respectively. Polyclonal antibodies were raised in rabbits against [9R]iP-BSA and were purified by affinity chromatography. Titers and specificity of the antisera and purified antibodies were determined by ELISA and RIA. These antibodies are highly specific for [9R]iP and do not cross-react with zeatin and ribosylzeatin. An immunoaffinity matrix was prepared with a capacity of 1 microgram of [9R]iP/mL of gel. PMID- 1616945 TI - A brief survey of methods for preparing protein conjugates with dyes, haptens, and cross-linking reagents. PMID- 1616947 TI - Preparation of novel cyclosporin A derivatives. AB - The hydroxyl group on the 2-N-methyl-(R)-((E)-2-butenyl)-4-methyl-L-threonine residue of cyclosporin A was protected by acetylation, then the double bond on the same amino acid residue was oxidatively cleaved using a periodate/permanganate reagent. The resultant derivative of cyclosporin A contained a carboxylic acid group which was subsequently reacted with the nucleophiles 5-(aminoacetamido)fluorescein and poly(L-lysine), in the presence of 1-ethyl-3-[3-(dimethylamino)propyl] carbodiimide, to furnish novel cyclosporin A conjugates. PMID- 1616946 TI - Gadolinium complexes of [(myristoyloxy)propyl]diethylenetriaminetetraacetate: new lipophilic, fatty acyl conjugated NMR contrast agents. AB - New lipophilic contrast agents, 1-[3'-(myristoyloxy)propyl]diethylenetriamine 1,4,7,7-tetraacetic acid (1MP-DTTA), 4-[3' (myristoyloxy)propyl]diethylenetriamine-1,1,7,7-tetraacetic acid (4MP-DTTA), and 4-[3'-(myristoyloxy)propyl]-2,6-dioxodiethylenetriamine-1,1, 7, 7-tetraacetic acid (4MPD-DTTA), were prepared from either diethylenetriamine or 3-amino-1 propanol (overall yield 16-23%). Liposome-incorporated Gd complexes of ligands 1MP-DTTA, 4MP-DTTA, and 4MPD-DTTA were prepared by mixing GdCl3 and the prepared vesicles consisting of ligand, egg lecithin, and cholesterol (molar ratio 1.1:5.1) followed by further sonication, and their in vitro relaxivities were determined. The relaxivities of these agents were higher than those of the Gd3+ aquoion, Gd(EDTA), or Gd(DTPA) at both 0.23 and 0.47 T. Gd(4MPD-DTTA) displayed the highest relaxivities (24.0 +/- 0.4 and 34.7 +/- 0.4, at 0.23 and 0.47 T, respectively) among these new Gd complexes. The relaxivities of these three agents increased from the lower to the higher magnetic field, indicating a positive field dependence. Stability constants (log K) of Gd(1MP-DTTA), Gd(4MP DTTA), and Gd(4MPD-DTTA) were found to be 18.2 +/- 0.2, 18.4 +/- 0.2, and 15.7 +/ 0.8, respectively. A lower limit of 0.3 mmol/kg was found for LD50 for these three agents. PMID- 1616948 TI - Preparation and characterization of a beta-lactamase-Fab' conjugate for the site specific activation of oncolytic agents. AB - Antibody-directed catalysis (ADC) is a two-step method for the targeted delivery of chemotherapeutic agents in which enzyme-antibody conjugates, prelocalized to antigen-bearing cells, activate prodrugs designed to be substrates for the enzyme. An enzyme-Fab' conjugate exhibiting both native beta-lactamase activity and immunoreactivity toward carcinoembryonic antigen (CEA) was constructed. Treatment of CEA-expressing LS174T cells with this conjugate imparted beta lactamase activity to the cells; beta-lactamase activity was not imparted by treatment with unconjugated beta-lactamase and not to CEA negative cells treated with conjugate. Cephalosporin-based prodrugs, and other substrates synthesized as model compounds, were found to have wide variations in their kinetic parameters toward the conjugate, with kcat values ranging from 16 to 3300 s-1 and KM values ranging from 5 to 160 microM. The prodrug derived from desacetylvinblastine-3 carboxylic acid hydrazide (DAVLBHYD) was studied in vitro and found to be 5-fold less cytotoxic to LS174T cells than the parent DAVLBHYD. For antigen-positive cells preincubated with conjugate, however, the prodrug showed the same potency as the parent drug. Thus, the combination of conjugate and prodrug appears to provide antigen-dependent toxicity to tumor cells. PMID- 1616949 TI - Synthesis, conformation, biodistribution, and in vitro cytotoxicity of daunomycin branched polypeptide conjugates. AB - Daunomycin has been attached to various structurally related synthetic branched polypeptides with a polylysine backbone, using its acid-labile cis-aconityl derivative (cAD). Due to the importance of the side-chain structure in alpha helix formation and immunological and pharmacological properties of branched polypeptides, we have investigated the conformation, biodistribution, and in vitro cytotoxicity of cAD-carrier conjugates with polypeptides containing amino acid residues of different identity and/or configuration at the side-chain end (XAK type) or at the position next to the polylysine backbone (AXK type), where X = Leu, D-Leu, Pro, Glu, or D-Glu. According to CD studies, polycationic conjugates with hydrophobic Leu in the side chains could assume a highly ordered conformation, while amphoteric conjugates containing Glu proved to be unordered in PBS. The reduction of in vitro cytotoxic activity of cAD by conjugation to carriers and the biodistribution profile of the conjugates were found to be dependent predominantly on the charge properties and on the side-chain sequence of the carrier polypeptide. It was demonstrated that by proper combination of structural elements of the carrier molecule, it is feasible to construct a cAD branched polypeptide conjugate with significantly prolonged blood survival and with no reduction in in vitro cytotoxicity of the drug. PMID- 1616950 TI - Rational design of a chimeric toxin: an intramolecular location for the insertion of transforming growth factor alpha within Pseudomonas exotoxin as a targeting ligand. AB - To investigate the potential utility of Pseudomonas exotoxin (PE) in forming rationally designed chemotherapeutic agents, we inserted a cDNA encoding transforming growth factor alpha (TGF alpha) at several locations in a gene encoding a mutant full-length PE (PE4E) which does not bind to the PE receptor. After expression in Escherichia coli, we purified the chimeric toxins to near homogeneity and showed that they were specifically cytotoxic to human epidermoid, ovarian, colon, and hepatocellular carcinoma lines. Like the previously reported TGF alpha-PE40, one of the new molecules (TGF alpha-PE4E) contains the ligand at the amino terminus. Two additional chimeras (PE4E-TGF alpha and PE4E-TGF alpha 598-613) each contain TGF alpha inserted near the carboxyl terminus of PE. We show that preservation of the correct PE carboxyl-terminal amino acid sequence, REDLK, allows the toxins containing TGF alpha carboxyl inserts to retain significant cytotoxicity against target cells, since another molecule (PE4E-TGF alpha-ILK) containing a nonfunctional carboxyl-terminal sequence was over 100 fold less active. The chimeric toxins with TGF alpha had the same binding affinity for the EGF receptor whether the ligand occupied the amino or carboxyl position. Molecules with TGF alpha near the carboxyl position were consistently less active against target cells but also less toxic to mice than those with TGF alpha at the amino terminus, indicating both types of molecules might be therapeutically effective. Our results establish that a ligand can be placed near the carboxyl terminus of PE, within the portion of the toxin that translocates to the cytosol. The amino-terminal position in such molecules is then available for the placement of other targeting ligands. PMID- 1616951 TI - Properties of chimeric toxins with two recognition domains: interleukin 6 and transforming growth factor alpha at different locations in Pseudomonas exotoxin. AB - Pseudomonas exotoxin (PE) is a potent cytotoxic agent that is composed of 613 amino acids arranged into three major domains. We have previously identified two positions where ligands can successfully be placed in PE to direct it to cells with specific surface receptors. One site is at the amino terminus and the other is close to but not at the C-terminus. To examine the possibility of constructing oncotoxins with two different recognition elements that will bind to two different receptors, we have placed cDNAs encoding either transforming growth factor alpha (TGF alpha) or interleukin 6 (IL6) at the 5' end of a PE gene and also inserted a cDNA encoding TGF alpha near the 3' end of the PE gene. The plasmids encoding these chimeric toxins were expressed in Escherichia coli and the chimeric proteins purified to near homogeneity. In all the new toxins, the TGF alpha near the C-terminus was inserted after amino acid 607 of PE and followed by amino acids 604-613 so that the correct PE C-terminus (REDLK) was preserved. For each chimera, the toxin portion was either PE4E, in which the cell binding domain (domain Ia) is mutated, PE40, in which domain Ia is deleted, or PE38, in which domain Ia and part of domain Ib are deleted. These derivatives of PE do not bind to the PE receptor and allow 607, 355, or 339 amino acids, respectively, between the two ligands.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616953 TI - Selective modification of cytosines in oligodeoxyribonucleotides. AB - A single deoxycytidine residing in an oligodeoxyribonucleotide which also contains 5-methyldeoxycytidines can be selectively derivatized with various alkylamines by sodium bisulfite-catalyzed transamination. Selective transamination results because 5-methylcytosine, unlike cytosine, does not form a bisulfite adduct. When the reaction is carried out at pH 7.1, transamination in the oligomer appears to occur to greater than 95% with little or no deamination. This procedure has been used to introduce aminoalkyl or carboxyalkyl side chains at the N4-position of a deoxycytidine in oligonucleotides. These side chains contain potentially reactive amine or carboxy groups which could serve as a sites for further conjugation of the oligomer with a variety functional groups. Oligonucleotides which carry these side chain form duplexes and triplexes with appropriate complementary single-stranded or double-stranded oligodeoxyribonucleotide target molecules. The stabilities of the duplexes are similar to those formed by unmodified oligomers, whereas the stability of the triplexes is approximately 18 degrees C lower than that formed by unmodified oligomers. PMID- 1616952 TI - Application of an N-(4-azido-2,3,5,6-tetrafluorobenzoyl)tyrosine-substituted peptide as a heterobifunctional cross-linking agent in a study of protein O glycosylation in yeast. AB - In order to investigate the O-mannosyltransferase involved in the initial O mannosylation of glycoproteins in Saccharomyces cerevisiae, a photoactive hexapeptide, [125I]-N-(4-azido-2,3,5,6-tetrafluorobenzoyl)-3-iodo-Tyr-Asn-Pro-T hr-Ser-Val ([125I]azidoTyr-peptide), was synthesized by solid-phase techniques using a new photoactive cross-linking reagent, N-(4-azido-2,3,5,6 tetrafluorobenzoyl)tyrosine, and resin-bound Asn-Pro-Thr(tBu)-Ser(tBu)-Val. When this modified hexapeptide substrate was incubated with O-mannosyltransferase preparations, the hexapeptide was an acceptor of [14C]-mannose from dolichol phosphate-[14C]mannose. After partially purifying the O-mannosyltransferase and photolabeling these enzyme preparations with [125I]azidoTyr-peptide, a ca. 82-kDa protein was shown to be the only apparent photolabeled protein that was protected by unmodified hexapeptide. This ca. 82-kDa protein may be the catalytic subunit of the O-mannosyltransferase. The susceptibility of the N-(4-azido-2,3,5,6 tetrafluorobenzoyl) moiety to reducing agents in aqueous buffers was also examined. PMID- 1616954 TI - An improved CPG support for the synthesis of 3'-amine-tailed oligonucleotides. AB - A new controlled-pore glass (CPG) support is described that allows for the direct synthesis of oligonucleotides bearing a 3'-aminohexyl tail. This solid support (AH-CPG) exhibits superior performance as compared to a commercially available 3' amine CPG. The AH-CPG is prepared from 6-aminohexan-1-ol with a unique protecting group for the amine that also functions as the site of attachment to the CPG. A 3'-amine-tailed oligodeoxynucleotide (ODN) was prepared from this support using standard phosphoramidite coupling and deprotection conditions. The 3'-amine tailed ODN was subsequently modified with an acridinylpropionic acid tetrafluorophenyl ester. Facile synthesis of the AH-CPG and the stability of the deprotected product makes this functionalized solid support especially useful for preparation of oligonucleotides bearing 3'-amine tails and other modifications. PMID- 1616955 TI - Synthesis of N-[6-(ethylenedioxy)hexyl]biotinamide: a biotinyl aldehyde precursor for labeling hydrazine-modified biomolecules. AB - Synthetic approaches for obtaining biotinyl aldehydes are described. While such aldehydes have limited shelflife, the acetal derivative, N-[6 (ethylenedioxy)hexyl]biotinamide, IX, was found to be indefinitely stable upon storage at -20 degrees C. Mild acid hydrolysis conveniently unmasks the aldehyde, which can then be used to label hydrazine-tagged biomolecules. PMID- 1616956 TI - Biochemical, immunological, and functional aspects of the growth suppressor/oncoprotein p53. AB - The cellular phosphoprotein p53 was initially discovered in a variety of in vitro transformed and tumor-derived cell lines. Later on, p53 was also found in normal, nontransformed cells albeit at very low levels. Inhibition of p53 functions by microinjection of anti-p53 antibodies prevented quiescent cells from reentering the cell cycle after serum stimulation, indicating that p53 might somehow be involved in the regulation of cell proliferation. After detection of p53-specific mRNAs, the gene was discovered in diverse species ranging from fish and frog to man. Knowing the p53 DNA sequence, it became clear that mutant forms of p53 had immortalizing and, in cooperation with other oncogenes, transforming activities. On the other hand, wild-type p53 could suppress oncogene-mediated transformation. It seems clear now that wild-type p53 is a tumor suppressor. Moreover, analysis of p53 from many types of human tumors indicates that the p53 gene is a very frequent target for mutational alterations. Because the biochemical consequences of these alterations are not yet clear, it is not understood yet on the molecular level how p53 can act as an oncogenic protein, on one hand, and as a growth suppressor protein on the other hand. Therefore, the present review aims to summarize the biochemical and immunological properties of p53 and to address some biological activities of p53 in order to allow more insight into how p53 might be regulated within the cell or how p53 might regulate cell proliferation. PMID- 1616957 TI - p53 from basic research to clinical applications. AB - Mutations on the TP53 tumor suppressor gene and allele loss on chromosome 17p, where this gene has been located, are among the most frequent alterations yet identified in human malignancies. The p53 protein is highly conserved through evolution and expressed in most normal tissues. Wild-type p53 has been shown to control normal cell proliferation possibly through transcriptional regulation. The wild-type TP53 gene can suppress cell transformation and neoplastic cell growth. In contrast, mutant TP53 has lost the tumor suppressing ability and, in most cases, has gained a transformation promoting ability. Many different TP53 mutations have common conformational and functional consequences on the p53 protein. However, all the TP53 mutants are not necessarily equivalent in terms of biological activity: some mutations confer a strong transforming ability, while others lead to truncated products with probably no biological function. Some mutants may exhibit a dominant behavior over wild-type TP53, others may be recessive. Point mutations of TP53 tend to occur on evolutionary conserved positions. However, the TP53 mutational spectrum differs among cancer types, and this fact may reflect different exogenous mutagens and endogenous factors contributing to human carcinogenesis. In defined types of malignancies, the tumors with TP53 alteration or tumors with allele loss on 17p are associated with more aggressive phenotypes than those without these alterations. For these malignancies, the monitoring of TP53 alteration should now be included in therapeutic trials. Germ line mutations on TP53 may also occur. Individuals with constitutional TP53 mutation have a predisposition to a wide variety of neoplasms. Further characterization of this predisposition will enable the definition of the best follow-up for these at-risk patients. PMID- 1616958 TI - Regulation of c-myc transcription initiation and elongation. AB - The c-myc protooncogene plays an important role in the regulation of cellular proliferation and differentiation. Selective downregulation of c-myc expression induces differentiation of leukemic cells, whereas constitutive overexpression prevents differentiation of the same cell types. The c-myc gene is comprised of three exons, the first of which is largely untranslated. Both c-myc mRNA and the c-myc gene product have very short half-lives, resulting in a very sensitive regulation of this important gene. Both transcriptional and posttranscriptional regulation of the c-myc gene expression have been documented. Transcriptional regulation can occur at the level of transcriptional initiation or elongation. A number of c-myc promoter-binding proteins have been identified and characterized. These include positive and negative regulatory factors. It appears that the c-myc gene is very tightly regulated in response to positive and negative growth stimuli. PMID- 1616959 TI - Factors inhibiting differentiation of myeloid leukemia cells. AB - Leukemic cells are arrested in less differentiated stages of development. However, there are many reports that various leukemic cells can be induced to differentiate into mature cells with attenuation of proliferative and leukemogenic activity. Mouse myeloid leukemia (Ml) cells both in vitro and in vivo can be induced to differentiate into macrophages and granulocytes by various compounds. During long-term culture of Ml cells, however, some populations of the cells spontaneously become resistant to induces of cell differentiation. The isolated resistant variant cell lines have higher leukemogenicity than parent cells and produce differentiation inhibitory protein factors (I-factor). The variant cell lines are useful to studies on how leukemic cells are arrested in less differentiated stages even in the presence of differentiation inducers both in vitro and in vivo. We have purified and characterized the I-factor. We review herein the properties of the I-factor and other inhibitory factors of differentiation of myeloid leukemia cells. PMID- 1616960 TI - Candida infections in AIDS patients. PMID- 1616961 TI - Congenital syphilis. PMID- 1616962 TI - Cryptococcal infection in AIDS. PMID- 1616963 TI - AIDS lymphomas. PMID- 1616964 TI - Improved outcome of Pneumocystis carinii pneumonia in AIDS patients: a multifactorial treatment effect. AB - Factors determining the outcome of an episode of Pneumocystis carinii pneumonia (PCP) in 149 AIDS patients treated at St Mary's Hospital were identified and their importance on improved survival evaluated between 1984 and 1989. The proportion of fatal episodes of PCP decreased over time. Fatal compared with nonfatal episodes had lower mean alveolar-arterial oxygen gradient (82.5 mmHg vs 53.8 mmHg, P less than 0.001), mean haemoglobin level (11.2 g/dl vs 12.1 g/dl, P = 0.01), mean lymphocyte count (0.68 x 10(9)/l vs 0.92 x 10(9)/l, P = 0.05) and more coinfections (31% vs 5%, P less than 0.001). Over time, the most significant change which occurred was a reduction in alveolar-arterial oxygen gradient at time of first presentation with PCP (r = -0.37, P less than 0.001). Mean alveolar arterial oxygen gradient declined from 79.9 mmHg in 1984 to 45.3 mmHg in 1989 (r = -0.88, P = 0.02), independently of zidovudine therapy or PCP prophylaxis. Patients were being treated at an earlier stage in their disease course as indicated by their reduced alveolar arterial oxygen gradient. This is due either to earlier patient presentation, earlier medical diagnosis or both. The widespread introduction of zidovudine and PCP prophylaxis may further contribute to improve morbidity and mortality patterns in the future. PMID- 1616965 TI - Prostatitis--clinical and bacterial studies. AB - Forty men with clinical prostatitis were studied to determine the value of symptomatology and categorization and 30 (75%) were classified as having prostatitis on the basis of prostatic localization studies. Of these 3 (10%) had chronic bacterial prostatitis, 18 (60%) had chronic abacterial prostatitis, and 9 (30%) had prostatodynia. No patient had acute bacterial prostatitis. Although Enterobacteriaciae were isolated from the 3 men with chronic bacterial prostatitis, these bacteria along with Staphlococcus aureus, Streptococcus faecalis, and Chlamydia trachomatis were isolated from a further 6 patients. The mean pH of the expressed prostatic secretion was measured for each group and was found to be 7.6 for those with chronic bacterial prostatitis, 7.1 for chronic abacterial prostatitis, 6.5 for prostatodynia, and 6.9 for those with urethritis suggesting that this test may be of value in the diagnosis of chronic bacterial prostatitis. PMID- 1616966 TI - A reappraisal of chlamydial and nonchlamydial acute non-gonococcal urethritis. AB - A cohort of 112 men presenting with acute non-gonococcal urethritis (NGU) was investigated for the presence of Chlamydia trachomatis. Men with 3 or more episodes of NGU in the preceding 12 months, or who had received treatment for NGU in the preceding 3 months were excluded. C. trachomatis was sought by examination of urethral smears by direct immunofluorescence, and by examination of the centrifuged deposit from a first pass urine (FPU) sample by direct immunofluorescence, IDEIA, and the polymerase chain reaction. Urethral samples from 48 men were positive for CT, and the FPU samples from an additional 7 men were positive by at least 2 assays. With such intensive investigation it is likely that those men identified as chlamydia-negative were genuinely free from the infection. The clinical history and response to treatment of those men who were chlamydia-positive were compared with those of the chlamydia-negative men. They differed in that a larger proportion of the chlamydia-positive men reported having had intercourse with more than one partner in the previous 3 months, and having had fewer previous episodes of NGU. Moreover, in contrast to some previous studies, after one week of treatment with doxycycline, a larger proportion (65%) of the chlamydia-negative men than the chlamydia-positive men (40%) was cured, although the difference was not sustained following later treatment. PMID- 1616968 TI - Radiological and histological features of intracerebral cryptococcomata. PMID- 1616967 TI - Comparison of ofloxacin and metronidazole for the treatment of bacterial vaginosis. AB - The efficacy and safety of ofloxacin, 200 mg twice daily for 7 days, was compared with metronidazole, 400 mg twice daily for 7 days, for the treatment of bacterial vaginosis (BV). Diagnosis of BV was confirmed by at least 3 of the following 4 criteria: the presence of an abnormal vaginal discharge on examination, clue cells on microscopy of vaginal specimens, vaginal pH greater than 5.0 and a positive amine test. Vaginal specimens were examined for Mobiluncus spp, analysed for the succinate/lactate (S/L) ratio and cultured for Trichomonas vaginalis, Gardnerella vaginalis, Bacteroides spp. and Mycoplasma hominis. Patients were reviewed on completion of treatment (visit 2) and 14 days later (visit 3). The diagnosis of BV was accepted in 119 of 149 patients recruited, 60 of whom received treatment with ofloxacin and 59 received metronidazole. Sixty-two patients, 31 in each treatment group, completed the study. Diagnostic cure at visit 2 was significantly better in the metronidazole group with cure rates of 56% (metronidazole) vs 23% (ofloxacin) (P = 0.001); this was associated with higher eradication rates for G. vaginalis (100% vs 56%) and Bacteroides spp. (97% vs 49%). There were no significant differences between the two groups in clinical cure at either visit 2 or 3 or in diagnostic cure at visit 3. Both treatments were well tolerated. We conclude that metronidazole is likely to remain the first choice of treatment for BV but ofloxacin offers a safe and effective alternative. PMID- 1616969 TI - Intestinal obstruction associated with genital herpes. PMID- 1616970 TI - Neisseriaceae and Moraxella sp.: the role of related microorganisms associated with conjunctivitis in the newborn. PMID- 1616971 TI - Malignant otitis externa in a patient with AIDS. PMID- 1616972 TI - Distal urethroscopy: a suggested modification of the meatoscopy technique. PMID- 1616974 TI - AIDS literature index. PMID- 1616973 TI - STD screening with molluscum contagiosum. PMID- 1616975 TI - Isolation of swine infertility and respiratory syndrome virus (isolate ATCC VR 2332) in North America and experimental reproduction of the disease in gnotobiotic pigs. AB - A recent epizootic of swine infertility and respiratory syndrome (SIRS) in a Minnesota swine herd was investigated. Examination of a sow, neonatal piglets, and stillborn fetuses obtained during the epizootic from the affected herd revealed interstitial pneumonitis, lymphomononuclear encephalitis, and lymphomononuclear myocarditis in the piglets and focal vasculitis in the brain of the sow. Fetuses did not have microscopic lesions. No cause for the infertility and respiratory syndrome was determined. Therefore, attempts were made to experimentally reproduce the disease. Eleven 3-day-old gnotobiotic piglets exposed intranasally to tissue homogenates of piglets from the epizootic became inappetent and febrile by 2-4 days postexposure and had interstitial pneumonitis and encephalitis similar to that seen in the field outbreak. After 2 blind passages in gnotobiotic piglets, tissue homogenates were cultured on continuous cell line CL2621, and a cytopathic virus (ATCC VR-2332), provisionally named SIRS virus, was isolated. Gnotobiotic piglets exposed intranasally to the SIRS virus developed clinical signs and microscopic lesions that were the same as those in piglets exposed to the tissue homogenates, and the virus was reisolated from their lungs. This is the first isolate of SIRS virus in the United States that fulfills Koch's postulates in producing the respiratory form of the disease in gnotobiotic piglets and the first report of isolation and propagation of the virus on a continuous cell line (CL2621). The virus is designated as American Type Culture Collection VR-2332. PMID- 1616976 TI - Characterization of swine infertility and respiratory syndrome (SIRS) virus (isolate ATCC VR-2332). AB - The characterization of an isolate of swine infertility and respiratory syndrome (SIRS) virus (ATCC VR-2332) is reported. A commercial cell line (CL2621) was used for the propagation of the virus for all assays. Laboratory studies indicate that this isolate is a fastidious, nonhemagglutinating, enveloped RNA virus. Cesium chloride-purified virions visualized by electron microscopy were spherical particles with an average diameter of 62 nm (range: 48-83 nm) and a 25-30 nm core surrounded by an envelope. Virus replication was restricted to the cytoplasm, as demonstrated by immunofluorescence. The virus did not react serologically with antisera to several common porcine viruses or with antisera to known viruses in the alphavirus, rubivirus, pestivirus, and ungrouped lactic dehydrogenase virus genera of the Togaviridae. However, convalescent sow sera and rabbit hyperimmune sera neutralized the SIRS virus at titers of 1:256 and 1:512, respectively. The virus was stable at 4 and -70 C, but was labile at 37 and 56 C. The properties of this isolate of SIRS virus resemble those of the family Togaviridae but do not match the described genera. PMID- 1616977 TI - Antigenic comparison of Lelystad virus and swine infertility and respiratory syndrome (SIRS) virus. AB - This study reports the antigenic relatedness of isolates of Lelystad virus collected in the Netherlands, Germany, and the United States. The binding of antibodies directed against these isolates was tested in a set of field sera collected during outbreaks of porcine epidemic abortion and respiratory syndrome in Europe and outbreaks of swine infertility and respiratory syndrome (SIRS) in North America. Two sets of sera from pigs experimentally infected with Lelystad virus or SIRS virus were also tested. Although all 7 isolates reacted with anti Lelystad virus sera, antigenic variation was considerable. The 4 European isolates resembled each other closely, but differed from the American isolates, and the 3 American isolates differed antigenically from each other. To reliably diagnose Lelystad virus infection, a common antigen must first be identified. PMID- 1616978 TI - Isolation of a cytopathic virus from weak pigs on farms with a history of swine infertility and respiratory syndrome. AB - Severe clinical signs of swine infertility and respiratory syndrome (SIRS) of unknown cause were observed in several Minnesota swine farms between November 1990 and March 1991. Forty-five lung samples of weak pigs were collected from 13 swine farms, and virus isolation was attempted using swine alveolar macrophage (SAM) cultures. A cytopathic virus was isolated from 19 lung samples collected from 6 different farms. Four pregnant sows were infected intranasally with a tissue suspension from which virus was isolated, and 4 6-week-old pigs and 2 contact pigs were infected intranasally with 1 of the isolates. The 4 sows farrowed 12 stillborn and 32 normal pigs. Virus was recovered from 10 of 19 pigs examined. Infected 6-week-old pigs were clinically normal except for slightly elevated rectal temperatures and mild respiratory signs. No or mild interstitial pneumonic lesions were observed in inoculated pigs, but the lesion was obvious in the 2 contact pigs. Seroconversion was observed in sows and pigs as measured by indirect fluorescent antibody (IFA). Serologic identification of the isolates was carried out by IFA using reference serum prepared from an experimentally infected sow. A cytoplasmic fluorescence was observed on the SAM monolayers infected with each of the 19 different isolates. Fluorescence was also observed when the monolayers were tested with SIRS virus ATCC VR-2332-infected sow sera. Replication of the isolates was not affected in the medium containing 5-iodo-2' deoxyuridine but was inhibited by treatment with ether. The isolates were relatively stable at 56 C and did not agglutinate with various erythrocytes tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616979 TI - An indirect fluorescent antibody test for the detection of antibody to swine infertility and respiratory syndrome virus in swine sera. AB - An indirect fluorescent antibody (IFA) test was developed and standardized to detect and quantitate antibody for swine infertility and respiratory syndrome (SIRS) virus in swine sera. Test results were evaluated using sera of pigs infected both experimentally and naturally with SIRS virus. The IFA test used swine alveolar macrophage (SAM) monolayers prepared in 96-well microplates and infected with SIRS virus. The monolayers were incubated with test sera, washed, and stained with fluorescein isothiocyanate-labeled rabbit anti-swine IgG. After another wash step, the monolayers were examined under a fluorescent microscope. A noninfected SAM control well was included for each sample. The antibody titers for each serum sample were recorded as the highest serum dilutions with specific cytoplasmic fluorescence but no fluorescence in the control wells. To evaluate the test, sera of 4 6-week-old pigs that had been infected with SIRS virus, 2 contact pigs, and 13 experimentally infected sows were used. In the experimentally infected pigs, antibody was first detected at 7 days postexposure (PE) and peaked (1:256-1,024) between 11 and 21 days PE. All 13 sow sera were negative at time of infection but were positive (1:64- greater than or equal to 1:1,024) at 14-26 days PE. Seven hundred twenty sera collected from 25 different swine farms with or without a history of SIRS were also tested. Of 344 sera from 15 swine farms with a clinical history of SIRS, 257 (74.7%) sera had IFA titers greater than or equal to 1:4, whereas 371 (98.7%) of 376 sera from herds with no history of SIRS were negative.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1616980 TI - Retrospective study of testicular degeneration in raccoons with canine distemper infection. AB - A 6-year (1985-1990) retrospective survey of raccoons with canine distemper infection and an outbreak of the disease in 1988 on South Island, South Carolina, are described. During this epizootic, 3 male raccoons with the clinical disease had gross testicular lesions that, on histopathologic examination, revealed severe diffuse degeneration and mineralization of seminiferous tubules. The testicular pathology of canine distemper in raccoons has not been previously reported. PMID- 1616981 TI - Antimicrobial resistance patterns and plasmid profiles of Streptococcus suis isolates. AB - Streptococcus suis isolates recovered from diseased animals in Quebec and western Canada and from human cases in Europe were tested for their susceptibility to different antimicrobial agents and screened for their plasmid content. Most isolates from Quebec were clindamycin, erythromycin, and tetracycline resistant; animal isolates from western Canada were notably less resistant to clindamycin and erythromycin, whereas human isolates were considerably more susceptible to most antimicrobials tested. More than 60% of isolates had plasmids that ranged from 1.5 to 35 kilobases (kb). Of the 7 plasmid profiles found, 2 were particularly frequent in isolates from Quebec and western Canada, suggesting the presence of epidemic strains in the swine population. A particular plasmid band of about 5 kb was present in most Canadian isolates. When this band was used as a probe in colony and Southern blot hybridization, most isolates harboring the 5-kb plasmid hybridized, even though their plasmid profiles were different. Human isolates from Europe differed in their plasmid content from Canadian isolates of animal origin. Although a high degree of antimicrobial resistance was associated with the presence of plasmids in most isolates, it was not possible to establish a causative relationship. PMID- 1616983 TI - Fungi associated with bovine abortion in the northern plains states (USA). AB - Mycotic infection was diagnosed in 6.8% of 6,858 cases of bovine abortion and stillbirth examined during a 9-year period. Aspergilli were associated with approximately 5% of all abortion cases and 71% of 446 cases that were cultured for fungi and diagnosed as mycotic abortion. Aspergillus fumigatus was the most frequent isolate (62%), followed by A. terreus (6.7%), Emericella (Aspergillus) nidulans (3.0%), A. flavus (2.9%), and E. rugulosus (less than 1.0%). Zygomycetes (Absidia, Mortierella, Rhizomucor, Rhizopus) accounted for 21% of the cases. Pseudallescheria boydii and yeasts (Candida, Torulopsis) were each identified in 2% of the cases. Fungi that uncommonly cause infection accounted for 2% of the cases and included Curvularia geniculata, Exophilia jeanselmei, Hendersonula toruloidea, Lecythosphora hoffmannii, Talaromyces flavus var. flavus (Penicillium vermiculatus), T. (Penicillium) thermophilus, and Wangiella dermatitidis. About 10% of the mycotic cases were mixed fungal infections involving A. fumigatus (87%), A. flavus (12.5%), or E. nidulans (12.5%) coexisting with Absidia corymbifera (72%), Rhizomucor pusillus (4.3%), or Rhizopus arrhizus (4.3%). In each mixed infection, both septate and nonseptate hyphae were observed in placental tissues. Twelve percent of the mycotic abortion cases were diagnosed by histologic examination alone because isolation attempts were negative or only formalin-preserved tissues were available. PMID- 1616982 TI - Etiologic agents detected in a 10-year study of bovine abortions and stillbirths. AB - During a 10-year period, specimens from 8,995 bovine abortions were submitted to the South Dakota Animal Disease Research and Diagnostic Laboratory; 8,962 of these specimens were suitable for examination. A supportable diagnosis was made in 2,942 (32.82%) of the abortions examined. An infectious cause was determined for 2,723 (30.38%) and a noninfectious cause for 219 (2.44%). Bacteria caused 1,299 (14.49%), viruses caused 948 (10.57%), and fungi caused 476 (5.31%). The infectious bovine rhinotracheitis virus was associated with 485 (5.41%) and the bovine viral diarrhea virus with 407 (4.54%). The most common noninfectious causes of abortion or stillbirth were anomalous development, 112 (1.25%); dystocia, 56 (0.62%); and twinning, 37 (0.41%). The cause of 6,020 (67.17%) abortions was not determined. Lesions, many suggesting the presence of infection, were present in 1,554 (17.34%) fetuses or placentas in which no infectious agent could be demonstrated. PMID- 1616984 TI - Serologic evidence incriminating a recently isolated virus (ATCC VR-2332) as the cause of swine infertility and respiratory syndrome (SIRS). PMID- 1616985 TI - A repository of specimens for comparison of diagnostic testing procedures for bovine paratuberculosis. PMID- 1616987 TI - Summary of bacterial isolates from farm-reared channel catfish (1979-1988). PMID- 1616986 TI - Evaluation of a commercial solid-phase enzyme immunoassay for the detection of ovine Chlamydia psittaci. PMID- 1616988 TI - Porcine Streptococcus suis in Minnesota. PMID- 1616989 TI - Erysipelothrix rhusiopathiae septicemia-polyserositis and streptococcal encephalitis in a calf. PMID- 1616990 TI - Enteric infection of a goat with enterohemorrhagic Escherichia coli (O103:H2). PMID- 1616991 TI - Clostridium chauvoei myositis infection in a neonatal calf. PMID- 1616992 TI - Prostatic hemangiosarcoma in a dog: clinical and pathologic findings. PMID- 1616993 TI - Hemopericardium in a dog due to hemorrhage originating in a heart base thymic remnant. PMID- 1616994 TI - The requirement of fibroblasts to confirm the identity of cytogenetic centric fusion (CF) carriers in same-sex twin cattle. PMID- 1616995 TI - Neuroendocrine tumor (paraganglioma) in an adult bovine. PMID- 1616996 TI - Sclerosing peritoneal mesothelioma in a dog evaluated by electron microscopy and immunoperoxidase techniques. PMID- 1616997 TI - Scoliosis and hydrocephalus in an ovine fetus infected with Toxoplasma gondii. PMID- 1616998 TI - Neospora-like protozoan infection as a cause of abortion in dairy cattle. PMID- 1616999 TI - Rapid identification of viable bacterial spores using a fluorescence method. AB - A method has been devised to differentiate viable and nonviable bacterial spores. "Germination-like" changes are initiated in spores with performic acid and lysozyme. The germinated spores are stained with aqueous acridine orange, a fluorescent dye. Nonviable spores fluoresce lemon-green and viable spores orange red. It is proposed that with the use of a membrane filter resistant to performic acid and lysozyme, the method may be used for spore enumeration in foods in about 4 hr compared to conventional plating methods, which usually require up to 72 hr. PMID- 1617000 TI - Adaptations of Goldner's Masson trichrome stain for the study of undecalcified plastic embedded bone. AB - Specialized adaptations for application of Goldner's Masson trichrome stain to plastic embedded undecalcified bone specimens are presented. This stain can be used successfully on methyl-glycol methacrylate, glycol methacrylate and Spurr embedded bones. The stain affords the advantage of good cellular staining due to the hematoxylin component with concomitant sharp discrimination of mature bone matrix which stains green, immature new bone matrix which stains red, and calcified cartilage which stains very pale green. Use of red filters during photomicrography aids in bone-osteoid discrimination in black and white photographs. PMID- 1617001 TI - Serial sectioning of insects with hard exoskeleton by dissolution of the exocuticle. AB - The method reported here was designed to produce paraffin serial sections as thin as 5 microns of insects or other arthropods with a hard cuticle. Heads and abdomens of Apis mellifera, Eristalomyia tenax and Tenebrio molitor were fixed with Schaffer's liquid, dehydrate with 80% ethanol, 90% ethanol, two changes of 100% isopropanol (2 hr each) and 12 hr in a 1:1 mixture of paraffin (58 C melting point) at 60 C. They were molded in paraffin after 12 hr of infiltration under a partial vacuum at 60 C. Large body openings of objects were sealed with paraffin to prevent infiltration of solvents. Thereafter, the outer paraffin was removed manually and with xylene (15 min); the cuticle was rehydrated with 100% isopropanol and 100% ethanol (15 min each). The objects were then treated with Sputofluol (Merck; a mixture of NaOH and NaClO) until they became white or their colorless endocuticle was stainable with aniline blue WS (C.I. 42755) after rinsing in a 50% acetic acid solution (v/v). They were then dehydrated with 100% ethanol and 100% isopropanol (15 min each) and subsequently re-embedded in paraffin. They were molded, sectioned, stained and mounted as usual. PMID- 1617002 TI - Rapid three-dimensional reconstruction at the light microscopic level and a technique for re-embedding the same semithin sections for electron microscopic examination. AB - Rapid three-dimensional reconstruction of serial sections at the light microscopic and ultrastructural levels was accomplished using a two-step technique. Fixed specimens were embedded in Epon and 1 microns sections were cut and placed on glass slides. One of every four sections was drawn onto transparency film for rapid three-dimensional reconstruction. The semi-thin sections were re-embedded in Epon and sectioned at 90 nm for examination in the electron microscopy. PMID- 1617003 TI - A pre-embedding reaction method for localizing NADH reductase and succinic dehydrogenase in skeletal muscle. AB - Paraffin wax embedding methods suitable for demonstrating the distribution of enzyme activity in tissues sections are uncommon; most procedures rely on the use of frozen section techniques. This paper describes a system for demonstrating certain enzymes which involves incubation of the tissue with appropriate substrates before a Paramat wax embedding procedure. While it has distinct merits of its own, the procedure is eminently suitable for use where a cryostat is not available; it can also be readily applied to other enzymes and tissues. PMID- 1617004 TI - Identification of the plant nucleolonema using silver staining of serial ultrathin sections. AB - A simple silver staining technique was applied to serial ultrathin sections of Vicia faba root tip meristems to investigate the structural organization of the nucleoli. The procedure consists of three steps: hydrophilic Lowicryl resin embedding, preparation of ribbons of serial ultrathin sections, and silver impregnation. This technique provided good contrast for a filamentous structure, previously called the "nucleolonema", in nucleoli at the light microscope level. Silver appears to react with some acidic proteins involved with ribosomal RNA transcription, since the major constituents of the nucleolonema are believed to be active rRNA transcriptional units. Tracing the nucleolonema through serial ultrathin sections strongly suggests that the nucleolonema is meandering and partly coiling within the nucleolus. The present technique permits identification of the nucleolonema in other plant species and investigation of its three dimensional structural organization. PMID- 1617005 TI - A microcomputer program for evaluating sampling error: an application to stereological methods for electron microscopy. AB - In situations where there is a need to minimize sampling error or sample size, the coefficient of variation (CV) may be used to evaluate sampling error as a function of the number of observations or subjects in a sample. For example, CV is useful for estimating the minimum number of electron micrographs (Nmin) required to obtain a representative field sample for stereological analysis. To facilitate the determination of Nmin, we have written a program (COEFficient) for DOS microcomputers which calculates CVs. COEF assists the user in reducing error to that which solely reflects biological variability, thereby minimizing the time and cost of subsequent analyses. PMID- 1617006 TI - Staining plant cells with silver. III. The mechanism. AB - Silver does not stain all cytological structures with the same intensity. The chemical basis for differential silver staining is unclear, but differences in protein side groups available to react with silver are likely involved. These include amine, carboxyl, phosphate, sulfhydryl and hydroxyl moieties. Here we report an investigation of the chemical groups that could be involved in salt nylon silver staining of onion root tip squashes. Based on the results, we conclude that SN silver staining primarily depends on the presence of tyrosine hydroxyl groups, and we propose a mechanism for staining. PMID- 1617007 TI - Growth factor requirements for DNA synthesis by Leydig cells from the immature rat. AB - Puberty in the male is dependent upon the elevated production of testosterone by the Leydig cells. LH affects this increase in testosterone output by increasing the total number of Leydig cells in the testis and by stimulating the steroidogenic pathway in these cells. Since Leydig cell proliferation is a prerequisite for the onset of puberty, we have examined the ability of LH and growth factors known to be present in the testis to promote DNA synthesis. Leydig cells were isolated from 21-day-old rats, cultured in serum-free medium for 48 h to become quiescent, and then treated with LH and growth factors for 18 h. [3H]Thymidine incorporation into DNA was assessed over the subsequent 4-h incubation period. Cells in control cultures incorporated low levels of [3H]thymidine into DNA and were stimulated after treatment with LH (100 ng/ml). Insulin/insulin-like growth factor-1 (IGF-1) and transforming growth factor-alpha (TGF-alpha), previously localized in Leydig cells by immunohistochemistry, also stimulated [2H]thymidine incorporation into DNA. The responses of the Leydig cells to maximum levels of insulin and TGF-alpha were dependent on the cell density. Insulin and TGF-alpha alone and in combination increased the number of cells labeled with [3H]thymidine, as assessed by autoradiography. TGF-beta, known to be secreted by Sertoli cells, also stimulated DNA synthesis under basal conditions, but the maximum response was significantly lower than that achieved in the presence of TGF-alpha.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617008 TI - Androgen maintenance of erectile function in the rat penis. AB - Previous research has shown that the frequency and duration of penile erection is diminished after castration and that replacement with testosterone will restore the process. Using rats, the present study was designed to confirm that erection is androgen-dependent and to determine whether castration and androgen replacement affect the penile vascular smooth muscle responsiveness to vasoactive drugs. Blood pressure in the corpus cavernosum was measured directly during erections induced by electrical stimulation of the autonomic innervation of the penis. Maximal cavernosal pressure was markedly reduced after castration but was returned to normal levels if the castrated animals were treated with testosterone. Infusion of nitroglycerin (vasodilator) or phenylephrine (vasoconstrictor) resulted in a decline in cavernosal pressure in androgen treated animals but not in castrated animals, even though the mean arterial blood pressure was strongly affected in all treatment groups by these drugs. When an inhibitor of nitric oxide synthesis was infused, cavernosal pressure was decreased in all groups, indicating that this substance is involved in penile erection. Taken together, these results show that androgens maintain the erectile process and may act specifically to support the responsiveness of the vascular smooth muscle to vasoactive drugs. PMID- 1617009 TI - Comparative studies of the antigens recognized by sperm-immobilizing monoclonal antibodies. AB - Characteristic properties of the antigens recognized by sperm-immobilizing monoclonal antibodies (SI-mAbs) from different sources were compared by ELISA competitive inhibition assay, Western blot analysis, chromatographic analysis, and enzymatic digestion studies. Among 9 SI-mAbs, human mAb H6-3C4 and three mouse mAbs--2C6, 2B6, and 2E5--also possessed strong sperm-agglutinating activity. Binding of human mAb H6-3C4 to sperm was strongly inhibited by the three mouse mAbs (2C6, 2B6, and 2E5), but not by the rat or the other four mouse mAbs. SDS-PAGE revealed that mAb H6-3C4 and three mouse mAbs recognized the same antigen molecules of 15-25 kDa present in both sperm extracts and seminal plasma. Chemical treatments with trifluoromethanesulfonic acid and sodium metaperiodate destroyed the antigen determinants recognized by the above four mAbs, as detected by both ELISA and antibody absorption tests. Western blot analysis revealed that the antigens were susceptible to treatments with papain, proteinase K, and N glycanase, but resistant to trypsin, V8 protease, and thermolysin. These results indicate that one of the major antigens recognized by mAbs with sperm immobilizing action may be a sperm membrane-associated glycoprotein of 15-25 kDa and the epitope may involve N-linked oligosaccharides. PMID- 1617010 TI - Effects of antiprogesterones on myometrial cell-to-cell coupling in pregnant guinea pigs. AB - We used intracellular microelectrodes to investigate the effects of the antiprogesterone (AP) compounds RU 486 and ZK 299 on cell-to-cell coupling in the guinea pig myometrium during pregnancy. The input resistance (Ro) of myometrial cells was high in nonpregnant tissues (44.6 +/- 6.39 M omega), but decreased by midgestation (Day 44 or 45 of gestation; 22.9 +/- 3.17 M omega), and was lowest at term (between 17.7 +/- 2.90 m omega and 13.1 +/- 4.34 M omega on Days 59-69). Treatment with the AP RU 486 or ZK 299 in three groups of midgestational animals reduced Ro to a similar level within 24 h. Lucifer Yellow (LY) was injected into smooth muscle cells as a direct but qualitative measure of metabolic coupling. In term and AP-treated animals, LY spread rapidly to neighboring cells within 60 sec, but little spread occurred in midgestational control tissues and no spread was seen even after 10 min in nonpregnant tissues. This correlation of decreased Ro (implying increased electrical coupling) with the development of extensive spread of LY indicates increased electrical and metabolical coupling between myometrial cells during labor. These data show that myometrial smooth muscle cells of guinea pigs are moderately well coupled before the onset of labor, and the coupling increases further, just prior to spontaneous delivery or due to treatment with APs. These events may be required for synchronizing and coordinating the electrical, metabolic, and contractile activity of labor. PMID- 1617011 TI - Preovulatory changes in the perifollicular capillary network in the rat: role of eicosanoids. AB - The aim of this study was to evaluate morphometrically the influence of ovulation inhibiting doses of indomethacin, an inhibitor of the cyclooxygenase pathway, and esculetin and caffeic acid, inhibitors of the lipoxygenase pathway, on the dilatation of the perifollicular capillary network in the theca interna. The development of the perifollicular capillary network as a function of follicular size and the changes in the vascular lumen were examined by light microscopy on a series of semithin cross sections of rat ovaries. The number of capillaries in the theca interna increased linearly with increasing follicle diameter. Thus, the relative number of capillaries in the theca interna supplying the avascular stratum granulosum remained constant. This indicates that follicular function is not regulated through changes in the number of capillaries in the theca interna. After hCG injection, an increase in the capillary area could be observed in follicles having a diameter of more than 600 microns. Indomethacin administration increased the capillary area of the ovulatory follicles as compared to the untreated side only at 6 h after treatment. By contrast, treatment with inhibitors of lipoxygenase resulted in a significant decrease in the capillary area of large follicles at all times examined (3, 6, and 9 h after hCG injection). Nevertheless, since both types of eicosanoid inhibitors suppressed follicle rupture, in spite of their opposing actions on the capillary area, it seems unlikely that their action on ovulation is primarily due to their effect on this parameter. PMID- 1617012 TI - Androgenic activity in 15-day-old male rats: role of the maternal pineal gland. AB - Female Sprague-Dawley rats, exposed to a long (18L:6D) or a short (6L:18D) photoperiod from 21 days of age, were mated when they reached 55 days of age. On Day 2 of gestation, dams were pinealectomized or sham-operated. Pre- and postnatal photoperiods were identical, and offspring were killed at 15 days of age. Maternal pinealectomy had no effect when rats were kept on 18L:6D. Rats born to sham-operated mothers and kept on 6L:18D had higher testicular testosterone and androstenedione content than offspring raised on the long photoperiod. This stimulatory effect of the short photoperiod was blocked by maternal pinealectomy and was not dependent on the offspring's own pineal since it was observed in both sham-operated and neonatally (on Day 5 after birth) pinealectomized rats. When sham-operated mothers housed on 18L:6D were treated daily during pregnancy and lactation by s.c. melatonin injection, there was an increase in the testicular testosterone content of offspring. It was concluded that when rats are maintained on a 6L:18D cycle the maternal pineal gland enhances the testicular testosterone and androstenedione content in 15-day-old offspring. This effect is probably mediated by maternally derived melatonin. At 15 days of age, the pineal of the offspring had no influence on testicular function. PMID- 1617013 TI - Regulation of ovarian antioxidant vitamins, reduced glutathione, and lipid peroxidation by luteinizing hormone and prostaglandin F2 alpha. AB - Reactive oxygen species are generated by the rat ovary, and they evoke marked antigonadotropic responses in ovarian cells. Protection against reactive oxygen species is provided by antioxidants such as vitamins C, E, and A, and reduced glutathione (GSH). Our objectives were to establish the ovarian levels of these antioxidants during development and regression of the corpus luteum of the pseudopregnant rat and to determine whether these levels were changed by an acute treatment with either a luteotropic (LH) or luteolytic (prostaglandin [PG] F2 alpha) agent. In addition, we evaluated the extent of oxidative activity in the ovary by determining the level of lipid peroxidation. Follicular development was associated with a significant increase in ovarian levels of vitamin A and GSH, whereas levels of vitamins E and C were unchanged. During the luteal phase, vitamin E levels tended to increase, whereas vitamin A and GSH levels decreased. Luteal regression was associated with a marked increase in ovarian levels of vitamins E and A, whereas GSH levels increased only transiently. Acute treatment with LH in the midluteal phase produced a transient decrease in vitamin C levels that was maximal at 4 h. Luteal vitamin E levels were markedly increased 24 h after LH treatment, whereas vitamin A levels were unchanged, and no evidence of lipid peroxidation was seen. Acute treatment with PGF2 alpha produced a transient decrease in luteal vitamin C levels coincident with transient lipid peroxidation and a sustained fall in serum progesterone levels. Ovarian vitamin A levels were elevated 24 h after PGF2 alpha treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617014 TI - Demonstration of oxytocin release by bovine luteal cells utilizing the reverse hemolytic plaque assay. AB - Corpora lutea (CL) of a number of species produce oxytocin (OXT). In the present experiments we studied basal, prostaglandin (PG) F2 alpha-stimulated and ascorbate-stimulated OXT release from individual bovine luteal cells utilizing the reverse hemolytic plaque assay (RHPA). Using a mixture of C- and N-terminus specific antisera against OXT, we were able to demonstrate OXT plaque formation by individual luteal cells. CL consist of two steroidogenic cell types: large luteal cells (LLC), believed to derive from granulosa cells and to produce and secrete OXT, and small luteal cells (SLC), thought to derive from theca cells. To distinguish between these two cell types, we designated cells greater than 20 microns as LLC and those less than 20 microns as SLC. On the basis of this morphological parameter, OXT release from both LLC and SLC was demonstrable. After an incubation period of 15 h, 7% of both cell types formed OXT plaques. PGF 2 alpha and ascorbate increased the size of plaques surrounding both LLC and SLC to more than 200% and 240%, respectively (basal plaque size = 100%). The number of plaque-forming cells increased only slightly in the presence of either PGF 2 alpha or ascorbate in comparison to basal conditions. We suggest that the RHPA can be used to demonstrate peptide release from luteal cells. It is concluded that LLC may be subdivided into functional subclasses because less than 10% of bovine luteal cells release OXT. Known OXT secretagogues increased the amount of OXT released. It appears that not only LLC but also SLC secrete this peptide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617015 TI - A quantitative comparison of the passage of capacitated and uncapacitated hamster spermatozoa through the uterotubal junction. AB - Female hamsters were artificially inseminated at the time of ovulation with an equal concentration and volume of capacitated sperm suspension in one uterus and uncapacitated sperm suspension in the contralateral uterus. When oviducts were examined 3.5-4.0 h after insemination, a significantly (paired t-test, p less than 0.05) lower number of spermatozoa were found in the oviduct from the side inseminated with capacitated sperm suspension compared to the side inseminated with uncapacitated sperm suspension. The reduction in the number of spermatozoa entering the oviduct on the side inseminated with capacitated sperm suspension was particularly evident when nearly all the spermatozoa in the suspension were hyperactivated. These results suggest that hamster spermatozoa require a progressive linear type of motility pattern to pass efficiently through the uterotubal junction and that under normal conditions in vivo, fertilizing spermatozoa initiate hyperactivated motility after entering the oviduct. PMID- 1617016 TI - Different neuroendocrine systems modulate pulsatile luteinizing hormone secretion in photosuppressed and photorefractory ewes. AB - The objective of this study was to determine whether two photoperiod regimens that induce anestrus in the ewe-short-day photorefractoriness (SDPR) and long-day photosuppression (LDPS)--act by different neuronal mechanisms. In separate experiments, ovary-intact (INTACT), ovariectomized (OVX), and ovariectomized estradiol-treated (OVX + E) ewes were subjected to three different photoperiodic regimens that resulted in reproductive quiescence: (1) exposure to long days (16L:8D), which caused photosuppression (INTACT, n = 9; OVX, n = 6; OVX + E, n = 5; (2) prolonged exposure to short days (10L:14D)), which caused photorefractoriness (INTACT, n = 10; OVX, n = 6; OVX + E, n = 5); (3) exposure to natural photoperiod, which induced seasonal anestrus (INTACT, n = 11; OVX, n = 6; OVX + E, n = 5). Effect of photoregimen was monitored by measuring progesterone or LH. Drug challenges were made after two sequential estrous cycles were missed in INTACT ewes, after mean LH concentrations dropped below 1 ng/ml in OVX + E ewes, and after LH interpulse intervals increased in OVX ewes. Effects of drug on LH pulse pattern were determined by taking blood samples at 12-min intervals for 8 h after i.v. diluent injection; then for 8 h after i.v. injection of cyproheptadine, a serotonin antagonist (3 mg/kg); and again 7 days later after i.v. injection of diluent or pimozide, a dopamine antagonist (0.25 mg/kg). Cyproheptadine had little effect except to decrease (p = 0.05) mean LH in INTACT anestrous ewes and decrease (p less than 0.01) pulse amplitude in OVX + E SDPR ewes. Pimozide did not affect LH pulse frequency in LDPS ewes. However, pimozide increased LH pulse frequency (p less than 0.005) and mean concentrations (p less than 0.005) in SDPR OVX + E ewes, whereas it suppressed LH pulse frequency (p less than 0.05) and amplitude (p less than 0.03) in SDPR INTACT and SDPR OVX ewes. The results suggest that (1) the role of the dopaminergic system differs in SDPR and LDPS ewes, and that different neuronal systems may effect SDPR and LDPS, (2) the effect of pimozide in SDPR ewes is altered by ovarian steroids, and (3) the serotonergic system has relatively little role in regulating pulsatile LH secretion in any of the three different states of anestrus. PMID- 1617017 TI - A similar distribution of gonadotropin isohormones is maintained in the pituitary throughout sexual maturation in the heifer. AB - Our working hypotheses for this study were that 1) the profile of intrapituitary LH and FSH isoforms would be shifted toward acidic forms as sexual maturation progresses in the bovine female; and 2) concentration of 17 beta-estradiol (E2) in circulation during sexual maturation would be a major factor modulating the percentage of the more acidic isoforms. In addition, the biological immunoreactive (B:I) ratios of each isoform of LH were evaluated at selected stages of sexual maturation. Heifers (7 mo of age) were assigned to one of three treatment groups: 1) ovariectomized (OVX; n = 16); 2) OVX and administered E2 (OVXE; n = 16); or 3) ovary-intact (INTACT; n = 14). Pituitaries were collected from heifers in each group at an estimated 120 days (prepubertal) of 25 days before puberty (peripubertal). A fourth group of 6 heifers remained intact (postpubertal INTACT) to determine time of puberty during the experimental period. Pituitaries of heifers assigned to the postpubertal INTACT group were collected during the follicular phase of the first or second estrous cycle postpuberty. Pituitaries were used for determination of relative amounts of gonadotropin isohormones. Tissue extracts of the pituitaries were chromatofocused on pH 10.5-4.0 gradients. The LH of all pituitaries resolved into thirteen isoforms that were designated isoforms A-L, and S, with isoform A the most basic form. Isoforms F and G (basic pH range) were the predominant isoforms of each chromatofocusing profile and comprised 50-60% of the immunoreactive LH. Isoforms J and K were the major isoforms eluting in the acidic pH range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617018 TI - Sites of estrogen uptake in embryonic Trachemys scripta, a turtle with temperature-dependent sex determination. AB - Female sex determination can be induced in embryonic red-eared slider turtles (Trachemys scripta) by exogenous estrogen, as well as by incubation at warm temperature. In the present study, estrogen target areas were identified in embryos before (stage 15), during (stage 18), and after (stage 22) the critical period for sex determination. Both hyperfilm and emulsion autoradiography were used to localize tritium accumulation after the injection of radiolabeled 17 beta estradiol. Site-specific tritium-labelling was found at all stages, notably in the mesonephros at stage 15, in the mesonephros and oviduct at stage 18, and in the mesonephros, oviduct, and the interrenal gland at stage 22. Few if any cells in the gonad were tritium-labeled at any stage. The large number of estrogen concentrating cells in the mesonephros and interrenal and the lack of binding to gonadal tissues indicates that estrogen action on gonadal differentiation during the period of sex determination may be indirect. PMID- 1617019 TI - Human leukemia inhibitory factor improves the viability of cultured ovine embryos. AB - Embryos were collected from ewes on Day 6 after estrus (Day 0 = estrus), placed in M2 culture medium, and assigned to 1 of 4 treatment groups. Some embryos were transferred to recipient ewes on Day 6 of their estrous cycle either in pairs (group 1) or singularly (group 2) within 3 h of collection. The remaining embryos were individually cultured for 48 h in an atmosphere of 5% CO2 in humidified air in either synthetic oviduct fluid (SOF) medium (group 3) or SOF containing 1,000 U/ml of recombinant human leukemia inhibitory factor (hLIF) (SOF + hLIF: group 4). These embryos were then transferred to recipient ewes on Day 8 of their estrous cycle. The addition of hLIF to culture medium significantly improved the development of the embryos compared with control embryos prior to transfer (blastocysts hatching from the zona pellucida: group 3 = 16% vs. group 4 = 64%, p less than 0.05; those degenerative: group 3 = 27% vs. group 4 = 9%, p less than 0.05) and the subsequent pregnancy rates of the recipient ewes, receiving a single embryo, at Day 70 of pregnancy (group 3 = 16% vs. group 4 = 50%, p less than 0.05). The pregnancy rate of ewes given embryos cultured for 48 h in SOF + hLIF prior to transfer (50%; group 4) was similar to the group 2 ewes receiving a single embryo soon after collection (52%), but the pregnancy rate for both groups was significantly lower than that for the group 1 ewes receiving two embryos soon after collection (89%: 53% twins, 36% singles; p less than 0.05). PMID- 1617020 TI - Proteins secreted from the early ovine conceptus block the action of prostaglandin F2 alpha on large luteal cells. AB - In this study we evaluated whether the early conceptus secretes a factor that blocks the action of prostaglandin (PG) F2 alpha on cultured ovine large luteal cells. PGF2 alpha inhibited progesterone production by lipoprotein-stimulated large luteal cells and this anti-steroidogenic action was blocked in a dose dependent manner by conceptus proteins secreted from Day 15 embryos. Purified ovine trophoblast protein-1 (oTP-1) did not exhibit the anti-PGF2 alpha activity, but secreted conceptus proteins devoid of oTP-1 did prevent the anti steroidogenic effects of PGF2 alpha. This activity does not appear to be a nonspecific effect of protein since neither serum albumin nor thyroglobulin, gamma globulin, insulin, LH, secreted ovine endometrial proteins, or heat inactivated secreted conceptus proteins had this action. After molecular-sizing chromatography we found a high- and a low-molecular weight fraction with luteal protective activity. Neither of the secreted conceptus protein fractions blocked the binding of 3H-PGF2 alpha to large luteal cells. However, conceptus proteins did block the anti-steroidogenic action of phorbol ester and calcium ionophore on large luteal cells, suggesting that secreted conceptus proteins act after activation of the free calcium/protein kinase C intracellular effector pathways. Thus, the early ovine conceptus secretes a luteal protective protein(s) that may be important for maintaining the corpus luteum during early pregnancy; however, the physiologic significance of this luteal protective protein(s) cannot be stated without further investigation. PMID- 1617021 TI - Influence of cell cycle stage of the donor nucleus on development of nuclear transplant rabbit embryos. AB - We evaluated the influence of the stage of the cell cycle of the donor nucleus on development in vitro of nuclear transplant rabbit embryos. The developmental potential of nuclei in early, mid-, and late stages of the cell cycle was determined. Duration of the G1 phase in early embryos was determined, and a procedure for reversibly synchronizing donor embryos in the G1 phase was developed. In addition, the extent of development in vitro of nuclear transplant embryos with donor nuclei synchronized in the G1 phase was evaluated. Development to blastocysts was greatly affected by the stage of the cycle of the donor nucleus. Use of early-stage nuclei led to 59% nuclear transplant blastocysts, whereas 32% and 3% were obtained with mid- and late-stage nuclear donors, respectively (p less than 0.001). The short duration of the G1 phase in 16- and 32-cell-stage embryos (approximately 30 min) necessitated a procedure for synchronizing blastomeres in the G1 phase. This entailed, first, a 10-h incubation in 0.5 micrograms/ml colcemid to arrest embryos in metaphase. After release from colcemid, embryos were allowed to cleave in 0.1 microgram/ml of the DNA synthesis inhibitor, aphidicolin, and remained blocked at the G1/S transition. This treatment was reversible, as assessed by the resumption of DNA synthesis, cleavage rate, and development to blastocysts of treated embryos. The beneficial effect of using early-stage donor blastomeres was confirmed by the enhanced rate of development of manipulated embryos to blastocysts with donor nuclei in the G1 phase (71%), as opposed to the late S phase (15%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617022 TI - Effect of donor cell cycle stage on chromatin and spindle morphology in nuclear transplant rabbit embryos. AB - We investigated the influence of the cell cycle stage of the nuclear donor on prematurely condensed chromatin (PCC) and spindle morphology and on chromosome constitution in rabbit nuclear transplant embryos. The configuration of PCC following nuclear transplantation with G1, early S, and late S phase donor nuclei (G1, early S, and late S transplants, respectively) was characterized in whole mounts and chromosome spreads. In addition, the influence of the donor cell cycle stage on chromosome constitution in cleavage stage-manipulated embryos was determined. Within 2 h after fusion of the donor blastomere, the recipient oocyte cytoplasm was able to induce formation de novo of a metaphase plate associated with a spindle in G1, early S, and late S transplants. Metaphase chromosomes and spindle were intact in most cases of PCC in G1 transplants. However, these structures displayed minor abnormalities in early S transplants and gross abnormalities in late S transplants, such as incomplete or absent spindle formation and incomplete chromatin condensation. Normal chromosomes were present in G1 and early S transplants, whereas chromosome abnormalities were detected in late S transplants. The results indicate that morphology of prematurely condensed G1 and early S chromatin has a minor influence on chromosome constitution of manipulated embryos. That of late S chromatin, however, affects chromosome constitution in embryos and may account for reduced development of nuclear transplant embryos when late S phase donor nuclei are used. PMID- 1617023 TI - Program for the 25th annual meeting of the Society for the Study of Reproduction. Raleigh, North Carolina, July 12-15, 1992. Abstracts. PMID- 1617024 TI - [The autologous transfusion concept--a legal necessity or a practical development? Are there consequences from the new BGH decision?]. PMID- 1617025 TI - [Anesthesia and acute hepatic porphyrias]. AB - Acute hepatic porphyrias are inherited disorders of heme biosynthesis. A characteristic feature of acute porphyrias is the occurrence of acute attacks which are often precipitated by drugs. Many of the commonly used anaesthetic agents may trigger such a potentially lethal attack. Thus, only safe agents should be administered to predisposed patients. Recommendations given are based on results from animal experiments and on a series of anecdotal reports. Regional anaesthesia is presented as anaesthetic technique of choice. General anaesthesia should be based on a fentanyl-nitrous oxide regimen, with propofol as induction agent. In the case of an acute attack, treatment consists of glucose and haematin administration. PMID- 1617026 TI - [Systematics and concept of a future integrated anesthesia device]. AB - On the grounds of the more than one hundred years lasting development of the anaesthesia machine the systematics of the components of a future integrated anaesthesia machine is described. The new generation of today's anaesthesia machine incorporates four main functions: dosing, ventilation, monitoring and data management. Given the achievements of the last 15 years in the fields of data and signal analysis, of the clinical pharmacology of intravenous anaesthetics, of measurement and evaluation of anaesthetic drug action, the four main functions are only partially realized in today's anaesthesia machines. Especially lacking are the integration of smart dosing devices for intravenous anaesthetics, the so-called "therapeutic monitoring" which monitors the efficacy of anaesthetic drug action, and a data management system which does not only manage data but interprets them in terms of "smart alarms" and maybe in the future also by expert systems. The concept of a future integrated anaesthesia machine is investigated via a study model and on the basis of a real model composed of already existing devices. PMID- 1617027 TI - [Are humidity filters necessary in the inspired air in the breathing circuit? A new in vivo method of measuring humidity in the air breathed]. AB - Humidification of inspiratory gases under anaesthetic conditions still is a matter of controversial discussion. Physiological humidification and heating of breathing air are preconditions for mucociliary clearance, pulmonary cleaning and defence mechanisms. These functions of the upper respiratory tract are eliminated by application of artificial airways. In general the humidification of inspiratory gases should not remain under 70% of relative air humidity at 37 degrees C. Under clinical conditions it is problematic to ensure sufficiently rapid and reproducible measurements of humidity during breathing cycles. We developed a measuring method that enables to make these measurements without big mechanical device. Aim of this investigation was to measure air humidity in typical semiclosed systems during anaesthesia and semiopen CPAP-respiration. The necessity and efficiency of a heat and moisture exchanger (HME) was to be investigated as well. After approximately 5 minutes there was an inspiratory relative air humidity not below 70% at 28 degrees C (19 mg H2O/l humid air) within the breathing circuit with CO2 double-absorber. By using an HME it is possible to increase relative air humidity within this system to 86% at 29.5 degrees C (25 mg/l). After one hour's respiration with this system without HME a relative humidity of 87% at 30 degrees C (26 mg/l) is reached after replaced HME. Initial relative humidity in a semiopen CPAP-system is about 12% at 28 degrees C (3 mg/l). This is increased to 85% at 29.5 degrees C (25 mg/l) after 15 minutes respiration with HME.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617028 TI - [Prophylactic administration of glucocorticoids prior to microlaryngoscopies?]. AB - Intravenous glucocorticoids before direct laryngoscopy? The necessity of a preventive injection of corticoids before direct laryngoscopy was determined in a prospective, double blind study. 51 patients, who underwent direct laryngoscopy under general anaesthesia, received either 250 mg methylprednisolone in 10 ml NaCl 0.9% (corticoid group) or 10 ml NaCl (NaCl group) intravenously one hour before laryngoscopy. Oedema formation and the degree of inflammation in the pharynx and hypopharynx were examined on the day prior to surgery and three to four hours postoperatively. Complications of the airways were noted in the immediate postoperative phase and at the time of the second examination. Direct laryngoscopy did not induce any significant change in oedema formation or degree of inflammation in both groups. However, there was a correlation between the duration of surgery and the degree of increase in oedema and inflammation in the NaCl group but not in the corticoid group. No difference between the groups was noted with regard to postoperative complications of the airways. Based on the present study, routine application of corticoids to prevent oedema after direct laryngoscopy cannot be recommended. PMID- 1617029 TI - [The pulmonary first pass effect of noradrenaline following intravenous and endobronchial administration for resuscitation]. AB - In a porcine CPR-model, we investigated the pharmacokinetics and pharmacodynamics of norepinephrine (NE) after intravenous (10 g/kg, n = 10, group A) and endobronchial (e.b., 100 micrograms/kg, n = 10, group B) administration. After 3 min of cardiac arrest induced by electroshock, restitution of spontaneous circulation (ROSC) was achieved in 8 animals in group A after 3.3 +/- 1.6 min, and in group B in 6 animals after 2.5 +/- 0.6 min. Haemodynamics during CPR were not significantly different, but during the first hour after ROSC e.b. NE showed a depot effect. Maximum venous (642 +/- 182 ng/ml after 3.5 +/- 0.3 min) and arterial (147 +/- 21 ng/ml after 4.2 +/- 0.4 min) NE concentrations in group A were significantly higher compared with values in group B (77 +/- 18 ng/ml after 5.5 +/- 0.5 min venous, 46 +/- 11 ng/ml after 6.0 +/- 0.7 min arterial). The area under the curve (AUC) in group A was calculated to be 55 +/- 12 ng/ml min (venous) and 35 +/- 7 ng/ml min (arterial) representing a pulmonary first-pass effect of 40%. In group B, the dose-adjusted AUC (39 +/- 13 ng/ml min venous, 30 +/- 10 ng/ml min arterial) represented a pulmonary first-pass effect of only 25%. Despite this lower pulmonary first pass, however, it is concluded that after e.b. administration of NE absorption is too much delayed and peak concentrations are too low. Therefore, NE should not be given via this route during CPR. PMID- 1617030 TI - [Amrinone for cardiovascular therapy in hypodynamic septic patients?]. AB - Pulmonary hypertension, systemic vasodilation and the supply dependency of oxygen uptake are the major problems associated with sepsis. Thus, the goal of haemodynamic therapy in septic patients is an increase in cardiac output large enough to permit adequate tissue oxygenation. The purpose of this study was to establish whether the additional use of the phosphodiesterase inhibitor amrinone is useful in hypodynamic septic patients with inadequate tissue perfusion. Nine patients who had developed the clinical signs of sepsis (temperature greater than 38.5 degrees C, leukocytosis greater than 15,000/mm3, thrombopenia less than 100,000/mm3 or a drop in platelet count greater than 30%, cardiovascular shock) were given amrinone 30 micrograms.kg-1.min-1 for one hour. All patients showed mixed venous oxygen saturations below 70% and oxygen extraction rates above 30%, despite maximum catecholamine therapy. Haemodynamic parameters were measured with the help of a pulmonary artery catheter. Statistical significance was checked using the Wilcoxon signed-ranks test. During amrinone application cardiac index increased significantly from 4.6.1.81.min-1.m-2 to 5.6 +/- 1.81.min-1.m-2 (p less than 0.01), while central venous pressure was kept constant by volume supply. Mean pulmonary artery pressure remained nearly unchanged, whereas mean arterial pressure dropped significantly from 91 +/- 13 mmHg to 75 +/- 8 mmHg (p less than 0.01). The oxygen supply rose during administration of amrinone by an average of 17%, which led to a rise in oxygen uptake. Independence of oxygen uptake from oxygen supply, however, could not be attained. In septic patients, amrinone increases cardiac output via pulmonary vasodilation. However, pronounced systemic vasodilation lowers arterial blood pressure, enhancing the risk of myocardial ischaemia. PMID- 1617031 TI - [Puncture sets for suprapubic catheter drainage of the bladder]. AB - Suprapubic fistula catheter drainage (SFC) has numerous important advantages compared with transurethral bladder drainage. Commercial SFC-sets should provide security and comfort to a high degree for patients and users in general, so that they can make profitable use of these advantages. The equipment of SFC-sets should be adapted to the site and circumstances of use. Therefore, we recommend the introduction of defined standard SFC-sets for application in intensive-care units. We describe 16 usual SFC-sets. Every single set possesses certain disadvantages. Improvements, especially as far as trocar and catheter are concerned, are necessary to lead to a further spread of the SFC-method, so that more patients can benefit from the method. Detailed hints for improvements and alterations are provided. PMID- 1617032 TI - [A case report on a 9-day-long abuse of propofol]. AB - This case report deals with the case of an alcohol-dependent, but abstinent patient, who took 3 x 5 ml/d (= 150 mg) propofol intravenously for nine days. Anxiety, inner tension and restlessness routine which had previously occurred during his daily vanished. No other psychotropic effects occurred. PMID- 1617033 TI - [Historic vignette (3). The narcotizer]. PMID- 1617034 TI - [How safe is isovolemic hemodilution in elderly patients at risk?]. PMID- 1617035 TI - Evaluation of new oral antimicrobial agents and the experience with cefprozil--a broad-spectrum oral cephalosporin. PMID- 1617036 TI - Pharmacology and pharmacokinetics of cefprozil. AB - Cefprozil is a new orally administered cephalosporin with a spectrum of in vitro activity similar to that of cefuroxime. The pharmacokinetics of cefprozil are linear relative to dose size. Gastrointestinal absorption produces maximal plasma concentrations of approximately 10 mg/L 1-2 hours after administration of an oral dose of 500 mg. Approximately 94% of the dose is absorbed, and 60%-70% is excreted in the urine as unchanged drug. The renal clearance exceeds the glomerular filtration rate, thus suggesting active tubular secretion. Administration with food or antacids produces negligible effects on the rate or extent of absorption. Kinetic disposition in the elderly is similar to that in young healthy individuals, but elimination is slightly slower in infants and children. Because renal impairment, but not hepatic dysfunction, significantly reduces the elimination of cefprozil, it is recommended that the dosage be reduced by 50% in patients whose creatinine clearance is less than 30 mL/min. Penetration of the interstitial fluid by cefprozil is excellent, with concentrations approaching those observed in the plasma. The pharmacokinetic disposition of cefprozil, coupled with its in vitro activity, supports the use of once- or twice-daily dosage regimens. PMID- 1617037 TI - Review of the in vitro antibacterial activity of cefprozil, a new oral cephalosporin. AB - Cefprozil is a newer oral cephalosporin with a spectrum of activity against organisms that include gram-positive and gram-negative pathogens. A review of published data shows that cefprozil is active (susceptibility, less than or equal to 8 micrograms/mL; moderate susceptibility, 16 micrograms/mL; resistance, greater than or equal to 32 micrograms/mL) against gram-positive species such as streptococci, methicillin-susceptible staphylococci, and Listeria monocytogenes; it may have marginal activity against some enterococci. Among the gram-negative species, cefprozil has activity against Escherichia coli, Proteus mirabilis, Citrobacter diversus, Klebsiella pneumoniae, Klebsiella oxytoca, Haemophilus influenzae, and Moraxella catarrhalis. For anaerobic species, cefprozil has activity against clostridial species, including Clostridium difficile, peptostreptococci, and possibly Bacteroides melaninogenicus and Eubacterium. The activity of cefprozil is generally greater than that of cephalexin and generally similar to that of cefaclor. In these reports, cefprozil showed more in vitro activity than cephalexin and cefaclor against penicillin-resistant pneumococci, penicillin-resistant viridans streptococci, beta-lactamase-positive methicillin susceptible Staphylococcus aureus, and C. difficile, although the clinical significance of some of these differences has yet to be studied. PMID- 1617038 TI - Current therapy for otitis media and criteria for evaluation of new antimicrobial agents. AB - Otitis media is the most commonly diagnosed disease in infants and children in the United States. For routine empirical treatment of uncomplicated acute otitis media, amoxicillin is the drug of choice. Persistence of signs and symptoms of infection during antimicrobial therapy calls for a change to an antibiotic effective against beta-lactamase-producing bacteria (e.g., trimethoprim sulfamethoxazole, amoxicillin/clavulanate, or one of the newer oral cephalosporins) or performance of tympanocentesis/myringotomy or both. The most common nonsurgical and surgical methods currently employed for prevention of frequent recurrences are antimicrobial prophylaxis, myringotomy with insertion of a tympanostomy tube, and adenoidectomy. For patients who have otitis media with effusion for which treatment is indicated, antimicrobial agents have been shown to be effective; amoxicillin is preferred as initial therapy. Guidelines for evaluating new antimicrobial agents in the treatment of otitis media are presented in this report. PMID- 1617039 TI - Comparison of cefprozil with other antibiotic regimens in the treatment of children with acute otitis media. AB - In two randomized clinical trials in children with otitis media, the efficacy and safety of cefprozil are compared to those of amoxicillin/clavulanate (n = 530) and of cefaclor and cefixime (n = 394). The rate of clinical cure or improvement was similar among patients receiving each drug regimen, ranging from 78% for amoxicillin/clavulanate to 89% for cefaclor; for cefprozil, this rate was 84% and 85% in the two studies, respectively. In the first study, cefprozil was superior to amoxicillin/clavulanate in the satisfactory clinical response rate for Streptococcus pneumoniae (P = .049), but response rates were similar for Haemophilus influenzae and Moraxella catarrhalis. Significantly more patients treated with amoxicillin/clavulanate (P less than .001) in the first study or cefixime (P less than .01) in the second study developed diarrhea than did those treated with cefprozil. We conclude that cefprozil therapy for otitis media in children produces clinical and bacteriologic response rates similar to those seen with amoxicillin/clavulanate, cefixime, or cefaclor. Furthermore, diarrhea was significantly less common with cefprozil than with cefixime or amoxicillin/clavulanate. PMID- 1617040 TI - Criteria for evaluation of antimicrobial agents and current therapies for acute sinusitis in children. AB - Acute sinusitis is a common complication of upper respiratory tract infections in children. The primary causative bacteria are Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Streptococcus pyogenes, and alpha hemolytic streptococci. Concurrent viral infection may confound interpretation of the clinical response to antimicrobial treatment. First-line antimicrobial treatment is usually with amoxicillin. The increase in frequency of beta lactamase-producing bacteria in some communities, however, may warrant empirical treatment with other drugs such as amoxicillin/clavulanate, trimethoprim sulfamethoxazole, cefixime, or cefuroxime. With the marketing of newer antimicrobial drugs for treating sinusitis, it is important for physicians to understand the criteria for evaluating the efficacy of each new drug in relation to existing antimicrobial agents. Criteria for clinical and bacteriologic evaluation of new antimicrobial drugs in the treatment of sinusitis in children are described. PMID- 1617041 TI - Streptococcal pharyngitis: current therapy and criteria for evaluation of new agents. AB - Penicillin has been the recommended drug of choice in most cases of group A streptococcus (GAS) pharyngitis for nearly 40 years based on its efficacy in the prevention of acute rheumatic fever. Since trials of other drugs for the prevention of rheumatic fever are no longer feasible in the United States, eradication of GAS pharyngitis has become the surrogate for their evaluation. On the basis of this criterion, specific therapeutic regimens have been recommended, and numerous other drugs have gained approval as alternatives to penicillin. Current therapeutic issues include possible decreased efficacy of penicillin, timing of the initiation of therapy, and drugs of choice for patients whose treatment fails, who are chronic carriers, or who have frequent infections. Criteria for assessment of new drugs include clinical response, likelihood of prevention of rheumatic fever, rates of relapse and recurrent infection, and drug safety. The establishment of uniform guidelines and definitions of response for new drug evaluations by the Infectious Diseases Society of America should aid in the further assessment of new antibacterial agents as therapy for GAS pharyngitis. However, no data yet suggest that any of these drugs should replace penicillin as the drug of choice. PMID- 1617042 TI - Treatment of pharyngitis and tonsillitis with cefprozil: review of three multicenter trials. AB - Cefprozil is a new oral cephalosporin with an in vitro spectrum of activity that includes group A beta-hemolytic streptococci (Streptococcus pyogenes). Three multicenter, randomized trials were conducted for comparing the clinical efficacy and safety of cefprozil administered once or twice daily with that of cefaclor, penicillin, or erythromycin ethylsuccinate administered three or four times daily in the treatment of mild-to-moderate tonsillopharyngitis. In the cefprozil cefaclor trial, the pathogen eradication rate for evaluable patients receiving cefprozil was 83%, which was significantly better than that for patients receiving cefaclor (76%) (P = .035). The rate of satisfactory clinical response was similar with cefprozil (89%) and cefaclor (84%). The overall response rate was significantly better with cefprozil (80%) than with cefaclor (72%, P = .018). Differences in response rates were not noted when analyzing only patients 2-12 years of age. In the cefprozil-penicillin trial, the eradication rate of bacteriologic pathogens was similar in patients receiving cefprozil (91%) and in patients receiving penicillin (87%). A satisfactory clinical response was seen in 95% of the evaluable cefprozil-treated patients, which was significantly better than the rate of satisfactory clinical response seen in the penicillin-treated patients (88%; P = .023). In addition, during-therapy cultures for penicillin treated patients yielded a significantly higher rate of beta-lactamase-producing Staphylococcus aureus than did those for the group of cefprozil-treated patients (13% vs. 4.5%, respectively; P = .046). Significantly more clinically symptomatic bacteriologic failures occurred in the penicillin group (P = .037).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617043 TI - Antibacterial therapy for lower respiratory tract infections in adults: a review. AB - Because of difficulties in accurately determining an etiologic diagnosis, the ideal treatment for acute community-acquired lower respiratory tract infections remains to be established. Suggested regimens, in the absence of persuasive findings from gram-stained preparations of sputum, are best guesses made on the basis of clinical and epidemiological data. Results from randomized controlled trials are only partially helpful since most trials require the isolation of a potential pathogen, a condition that excludes as many as half of all potential study participants. Nonetheless, initial therapy for patients producing phlegm with abundant polymorphonuclear leukocytes should be chosen on the basis of the predominant organisms seen on a stained sputum smear. Patients who are admitted to the hospital from home, greater than 50 years of age, and not producing phlegm can be safely treated with amoxicillin or a second-generation cephalosporin. Atypical pneumonia in younger patients is best treated with erythromycin or tetracycline. Patients admitted from nursing homes, who frequently fail to respond to an initial treatment course in the absence of a diagnostic sputum sample, should receive empirical therapy with an agent that is also active against aerobic gram-negative rods. PMID- 1617044 TI - Review of the experience with cefprozil for the treatment of lower respiratory tract infections. AB - A regimen of cefprozil (500 mg twice daily), a new oral cephalosporin with a broad in vitro spectrum of antimicrobial activity, was compared to standard regimens of cefaclor (500 mg three times daily), cefuroxime axetil (500 mg twice daily), or amoxicillin/clavulanate (500 mg/125 mg three times daily) for the treatment of lower respiratory tract infections (mainly bronchitis and acute exacerbations of chronic bronchitis) in adults in three open-label, randomized trials. In the first trial, in which bacterial pathogens were isolated in initial cultures for only one-third of the patients, 90% of the pathogens were susceptible to cefprozil. A satisfactory clinical response was noted for 84% of the evaluable patients who received cefprozil versus 79% of those who received cefaclor for treatment of lower respiratory tract infections; rates of bacteriologic efficacy were 82% and 78%, respectively. In the second study rates of satisfactory clinical response were 96% with cefprozil and 83% with cefuroxime axetil (P less than .03) for treatment of bronchitis; the respective bacteriologic response rates were 100% and 92%. In the third trial, clinical efficacy was 91% for cefprozil and 87% for amoxicillin/clavulanate for treatment of bronchitis; bacteriologic efficacy was 95% and 96%, respectively. Tolerability and safety profiles were comparable, except that there was a higher rate of diarrhea among patients who received amoxicillin/clavulanate (P = .03). PMID- 1617045 TI - An approach to evaluating antibacterial agents in the treatment of urinary tract infection. AB - The evaluation of antibacterial therapy for urinary tract infection (UTI) is based on the results of randomized, controlled comparative studies (preferably double-blinded) in which sufficient numbers of patients are entered into both arms to ensure statistical validity. Since the term UTI encompasses a broad array of clinical syndromes (acute uncomplicated UTI; acute uncomplicated pyelonephritis; complicated UTI; and asymptomatic bacteriuria), the design of clinical studies should include a careful definition of the clinical syndromes being studied, the course of therapy prescribed, and the microbiological characterization necessary for evaluability. End points to be considered in the evaluation of new therapies include the effect of therapy on clinical symptoms; the ability of the therapy to eradicate the original infecting organism; the incidence of reinfection posttherapy; the number of instances of primary drug resistance of the infecting inoculum; and the incidence of adverse effects with a particular regimen. PMID- 1617046 TI - Clinical trials of cefprozil for treatment of skin and skin-structure infections: review. AB - Limitations of currently used antimicrobial agents for the treatment of skin and skin-structure infections (e.g., increased resistance to penicillin and erythromycin and inconvenient dosing schedules) have led to an adjustment in the kinds of antimicrobial agents prescribed for these diseases. Three recently completed clinical studies have demonstrated some therapeutic advantages of cefprozil, a new broad-spectrum oral cephalosporin, over cefaclor and erythromycin in the treatment of skin and skin-structure infections. Specifically, cefprozil offers clinical efficacy equivalent to those of cefaclor and erythromycin both at lower total doses and on a less frequent dosing schedule (once or twice daily vs. three to four times daily). The advantage of once-daily or twice-daily dosing with cefprozil may contribute to patient convenience and compliance. PMID- 1617047 TI - Safety profile of cefprozil. AB - The clinical and laboratory safety of cefprozil was analyzed with data from 4,227 patients who received the drug in North American and European clinical efficacy trials. Of these patients, 3,016 adults and children received capsules or tablets, while 1,211 patients (mostly children) were treated with cefprozil suspension. Cefprozil was used in single-daily or twice-daily dosing regimens for treatment of infections of the upper and lower respiratory tracts, sinuses, middle ear, urinary tract, and skin and skin structure. The incidence of adverse clinical events and laboratory abnormalities was similar to that associated with use of other oral cephalosporins. Gastrointestinal adverse effects were the predominant adverse clinical event, although the incidence of diarrhea with cefprozil was much lower than that with cephalosporins that are less well absorbed. The data confirm the safety of cefprozil in both adult and pediatric patients. PMID- 1617048 TI - Mycobacterial diseases other than tuberculosis. AB - The incidence of tuberculosis in the United States declined steadily until 1985, while at the same time, for at least the past 15 years, the frequency of disease attributable to other mycobacteria increased both in actual numbers and in the proportion of the total burden of mycobacterioses. Chronic pulmonary disease, lymphadenitis in children, skin and soft-tissue involvement, and infections of the skeletal system were predominant, and the principal etiologic agents were Mycobacterium avium/Mycobacterium intracellulare complex. Mycobacterium kansasii, Mycobacterium marinum, Mycobacterium fortuitum/Mycobacterium chelonae complex, and Mycobacterium scrofulaceum. Since 1986 disseminated disease has become not only more common, especially in association with opportunistic infections in patients with AIDS, but also attributable in part to the growing population of patients who are immunocompromised because of malignancy, receipt of an organ transplant, and administration of steroids. Treatment of these patients has been difficult because of the frequency of severe underlying conditions and the natural resistance of most of the nontuberculous mycobacteria to the presently available drugs. PMID- 1617049 TI - Pneumococcal antimicrobial resistance: the problem in Hungary. AB - An epidemiological survey of penicillin resistance as determined by minimum inhibitory concentrations (MICs) in Streptococcus pneumoniae strains collected from several Hungarian laboratories in 1988-1989 indicated a prevalence of 58% among a total of 135 isolates. A significantly higher resistance rate (69.2%) was found for isolates from pediatric patients than from adult patients (44.0%). Penicillin-resistant strains were more frequently resistant to non-beta-lactam antibiotics (tetracycline, erythromycin, co-trimoxazole, and chloramphenicol) than were penicillin-sensitive strains. On the basis of the MIC50 and MIC90 values of ampicillin and five cephalosporins for penicillin-resistant strains, it was established that ampicillin and cephalexin were not superior to penicillin. The low MIC90 of ceftriaxone and cefotaxime for these organisms reflects promising therapeutic potential, even in septicemia and meningitis caused by penicillin-resistant strains. The therapeutic alternative to penicillin in the treatment of respiratory tract infection may be second-generation cephalosporins such as cefuroxime or cefamandole. PMID- 1617050 TI - Geographic distribution of penicillin-resistant clones of Streptococcus pneumoniae: characterization by penicillin-binding protein profile, surface protein A typing, and multilocus enzyme analysis. AB - Examination of several hundred penicillin-resistant clinical isolates of Streptococcus pneumoniae has revealed extensive strain-to-strain variation in the number and molecular size of penicillin-binding proteins (PBPs). This polymorphism has been used to classify resistant isolates into groups (PBP families) that share distinct electrophoretic profiles. We describe herein properties of four such PBP families: two from Spain (and/or Ohio) and one each from Hungary and Alaska. We have discovered that representative isolates assigned to each PBP family also share capsular serotype, antibiotic resistance pattern, pneumococcal surface protein A type, and multilocus enzyme genotype. The results demonstrate independent clonal origin for strains assigned to each PBP family. Each resistant clone occurs with uniquely high incidence within specific geographic areas. PMID- 1617051 TI - Treatment and diagnosis of infections caused by drug-resistant Streptococcus pneumoniae. AB - Drug-resistant strains of Streptococcus pneumoniae have now been reported from all continents and have become the predominant pathogens in some areas; many strains are resistant to multiple agents. Because of the importance of pneumococci in the etiology of meningitis, the criteria used to assess susceptibility are conservative: strains with minimal inhibitory concentrations (MICs) of penicillin G of less than or equal to 0.06 microgram/mL are regarded as susceptible, those with MICs of 0.1-1 microgram/mL are considered intermediately resistant, and those with MICs of greater than 1 microgram/mL are designated highly resistant. The diagnosis, treatment, and prevention of infections due to resistant pneumococci are the subjects of this review. Methods of susceptibility testing have now been well defined for pneumococci. Screening for penicillin resistance with 1-microgram oxacillin disks is recommended for all clinically significant isolates. The activity of other beta-lactam agents against penicillin resistant strains has been documented, and the MICs of a number of non-beta lactam agents have been determined as well. Treatment of resistant pneumococcal infections depends on the site of infection, the degree of resistance to penicillin G, the resistance of the infecting strain to other agents, the severity of disease, the presence of underlying conditions, and the dose and route of administration of antimicrobial agents. Current recommendations for treatment are based on retrospective case studies, and adequate prospective studies providing more definitive data are needed. Prevention of pneumococcal infections in children less than 2 years of age and in the elderly remains a problem. Improved vaccines must be developed for this purpose. PMID- 1617052 TI - Yeast perinephric abscess: report of a case and review. AB - We report a case of yeast perinephric abscess and review 11 other published cases. This rare entity occurs primarily in patients who have diabetes mellitus, who have recently undergone surgery, or who have urinary tract obstruction. The clinical illness is often subacute or chronic with nonspecific symptoms. Candida and Torulopsis species are the reported etiologic agents. Successful therapy usually consists of percutaneous or surgical drainage of the abscess. Overall mortality is 25%; however, no patient in this series died as a direct result of perinephric infection. PMID- 1617053 TI - Diagnosis of infection with the human immunodeficiency virus. AB - The development and subsequent widespread use of accurate, sensitive, and relatively inexpensive diagnostic tests for infection with the human immunodeficiency virus (HIV) have been critically important in mapping the spread of the virus and managing HIV-infected individuals. Although the ELISA (for screening) and western blot (confirmatory test) techniques have, for the most part, fulfilled these criteria, interpretation of results of these tests is not always as straightforward as would be ideal. For example, what is the significance of an indeterminate western blot? How many times should the test be repeated? When can the patient be told he/she is truly HIV antibody negative? In this AIDS Commentary, Drs. John P. Phair and Steven Wolinsky of the Department of Medicine at Northwestern University Medical School address these questions and present their thoughts on these timely and extremely important issues. PMID- 1617054 TI - Emergence of unusual opportunistic pathogens in AIDS: a review. AB - Opportunistic infections are a major cause of morbidity and death among patients infected with the human immunodeficiency virus (HIV), particularly late in the disease, when immunosuppression is severe. Some pathogens, such as Pneumocystis carinii and Toxoplasma gondii, are extremely common in this population and are readily recognized by clinicians caring for these patients. However, many other organisms occasionally cause conditions that clinically mimic the more commonly encountered pathogens. Clinicians must be alert to the threat posed by these less frequently occurring organisms and of the broader differential diagnosis that must be considered for infections in patients with HIV infection. PMID- 1617055 TI - Cutaneous tuberculosis: a rare presentation of malignancy. AB - An 88-year-old woman presented with fever, a neck ulcer, and multiple subcutaneous nodules on her upper extremities and thorax. Her condition was initially diagnosed as malignancy associated with metastatic disease to the skin. A subcutaneous nodule was aspirated. A gram stain of the aspirate revealed weakly gram-positive bacilli, and a stain for acid-fast bacilli was positive. Mycobacterium tuberculosis was isolated from a culture of a specimen of the skin lesion. PMID- 1617056 TI - Mycobacterium xenopi, Mycobacterium fortuitum, Mycobacterium kansasii, and other nontuberculous mycobacteria in an area of endemicity for AIDS. AB - Between 1981 and 1990, cultures of specimens from 86 patients at State University of New York-Health Sciences Center at Brooklyn were positive for nontuberculous mycobacteria other than Mycobacterium avium/Mycobacterium intracellulare complex or Mycobacterium gordonae. The most common species isolated were Mycobacterium xenopi (33), Mycobacterium fortuitum (28), Mycobacterium kansasii (7), and Mycobacterium chelonae (6). Thirty-five patients (41%) had clinical and/or serological evidence of human immunodeficiency virus (HIV) infection. Patients from whom M. xenopi and M. kansasii were isolated were significantly more likely to be infected with HIV than were the remaining patients in this series. Most of the mycobacterial isolates were cultured from respiratory secretions. However, extrapulmonary infections with M. fortuitum, M. xenopi, M. kansasii, Mycobacterium terrae, and Mycobacterium scrofulaceum did occur among the HIV infected patients. PMID- 1617057 TI - Neurological melioidosis: seven cases from the Northern Territory of Australia. AB - Pseudomonas pseudomallei, which causes melioidosis, is most commonly associated with pulmonary infection. We describe seven patients who developed a neurological syndrome as the predominant manifestation of melioidosis: this syndrome was characterized by peripheral motor weakness (mimicking Guillain-Barre syndrome), brain-stem encephalitis, aseptic meningitis, and respiratory failure. Neurological melioidosis occurred in the absence of demonstrable foci of infection in the central nervous system (CNS) in five of six patients whose cerebrospinal fluid was available for culture. Computed tomography and magnetic resonance imaging of the brain and spinal cord of these patients were not suggestive of pyogenic infection, although the latter procedure detected brain stem encephalitis. Autopsy findings in one case confirmed brain-stem encephalitis without evidence of direct bacterial infection. The clinical presentation of neurological melioidosis includes features of an exotoxin-induced neurological syndrome, with profound neurological disease occurring in the absence of apparent direct infection of the CNS. This syndrome appears to be a newly recognized clinical presentation of melioidosis. PMID- 1617058 TI - Primary cutaneous fungal infection after solid-organ transplantation: report of five cases and review. AB - Solid-organ transplant recipients who are receiving immunosuppressive therapy are at increased risk of acquiring opportunistic infections, particularly fungal infections. We present the cases of five liver transplant recipients who developed primary cutaneous opportunistic fungal infections that remained localized to the skin. These cases are compared with 27 previously reported cases of primary cutaneous fungal infections. In these previously reported cases, administration of systemic antifungal medications, including amphotericin B, ketoconazole, griseofulvin, and miconazole, resulted in a 71% survival rate. Medical and surgical therapy together resulted in an 86% survival rate, and surgical excision resulted in a 100% survival rate. Thus, regardless of the age of the patient, type of immunosuppressive therapy, clinical presentation, or organisms involved, surgical excision yielded the highest cure rate. When possible, surgical excision should be performed on solid-organ transplant recipients who acquire opportunistic fungal infections. PMID- 1617059 TI - Prevention of neonatal infection with herpes simplex virus. PMID- 1617060 TI - Infective endocarditis due to Staphylococcus capitis. PMID- 1617061 TI - Pyogenic sacroiliitis due to Veillonella parvula. PMID- 1617062 TI - Nasal tuberculosis: two cases in elderly patients. PMID- 1617063 TI - Listeriosis and cephalosporins. PMID- 1617065 TI - Severe cholestatic jaundice caused by mezlocillin. PMID- 1617064 TI - Bacteremia due to Campylobacter cinaedi in a patient infected with the human immunodeficiency virus. PMID- 1617066 TI - Central nervous system tuberculoma presenting as a cavernous sinus tumor. PMID- 1617067 TI - Acute toxoplasmic hepatitis in a patient with AIDS. PMID- 1617068 TI - Bacteremia and fungemia of unknown origin among patients receiving intensive care. PMID- 1617069 TI - Prosthetic valve endocarditis and paravalvular abscess caused by Peptostreptococcus magnus. PMID- 1617070 TI - Medical management of spinal epidural abscesses: case report and review. AB - Although the traditional management of spinal epidural abscesses includes antibiotic therapy and surgical drainage, numerous reports have appeared in the literature that describe a nonsurgical approach. We report the successful nonsurgical management of a case of an extensive spinal epidural abscess in which the patient was closely monitored by serial studies with magnetic resonance imaging. Review of the literature from 1970 to 1990 revealed 37 cases that describe conservative management of spinal epidural abscesses. Despite successful conservative management reported for some cases, sudden neurological deterioration of patients receiving appropriate antibiotic therapy has also occurred. A true index of the success of nonsurgical therapy is difficult to discern since cases may have been selectively reported and unsuccessful attempts at conservative management may have never been reported once a laminectomy was performed. A prospective investigation that includes clearly defined indications for conservative management vs. surgical intervention and that can be studied with an intention-to-treat analysis is needed. PMID- 1617071 TI - To decompress or not to decompress--spinal epidural abscess. PMID- 1617072 TI - Streptococcal and enterococcal bacteremia in patients with cancer. AB - Eighty-two episodes of bacteremia due to streptococci (including the genus Enterococcus) in 78 patients hospitalized at Institut Jules Bordet between 1986 and 1988 were reviewed. The incidence ranged from 5.5 to 7.6 per 1,000 admissions (16% of all bacteremias). Enterococcus faecalis, Streptococcus sanguis, and Streptococcus mitis were the most prevalent isolates, followed by Streptococcus angionosus, Streptococcus salivarius, and large colony-forming beta-hemolytic species (A, B, C, and G). Twenty-one episodes were polymicrobial. One-half of the patients had solid tumors, and one-half had hematologic malignancies. Forty-two patients were neutropenic (less than 1,000 polymorphonuclear neutrophils/microL). Only 15 episodes were acquired outside the hospital, and 11 episodes were breakthrough bacteremias. Twenty patients died within 1 month of the onset of streptococcal bacteremia. Five patients, two of whom were neutropenic, had fatal adult respiratory distress syndrome. The source of bacteremia remained undetermined in 35.4% of the episodes; the oral mucous membrane and the gastrointestinal tract were the most frequently recognized associated sites of infection. No unexpected antimicrobial resistance was observed except in two penicillin-resistant strains, one S. mitis and one E. faecium. No relation between peak or trough serum bactericidal titers and outcome could be demonstrated. PMID- 1617073 TI - Nosocomial bacteremia due to Enterococcus faecalis without endocarditis. AB - During a 2-year observation period at a 2,200-bed university hospital, bacteremia due to Enterococcus faecalis was observed in 111 patients. Fifty-five patients with nosocomial bacteremia due to E. faecalis could be evaluated. The most common entry sites were the urinary tract (25%), the intraabdominal cavity (13%), and burn and decubital wounds (11%). Bacteremia was preceded by administration of cephalosporins, imipenem, and aztreonam (n = 39); ciprofloxacin (n = 11); and other antibiotics (n = 4). Age, sex, underlying disease, portal of entry, previous antibiotic therapy, and bacteremia due to other organisms had no influence on mortality. Treatment of bacteremia with penicillins (n = 45) and glycopeptides (n = 4) resulted in a mortality rate of 37%. The addition of a high dose aminoglycoside to a penicillin did not result in a better survival rate. PMID- 1617074 TI - Enterococcal endocarditis. AB - Enterococci, most often Enterococcus faecalis, cause 5%-20% of cases of infective endocarditis (IE). Enterococcal IE is usually a disease of older men, and the most frequent source of infection is the genitourinary tract. In cases of enterococcal IE, both normal and previously damaged valves can be involved. The disease most commonly presents in a subacute fashion; clinical and laboratory features are similar to those observed with IE caused by other pathogens. Diagnosis is based on the presence of clinical criteria of IE in association with positive blood cultures. Optimal therapy entails the parenteral use of a cell wall-active agent (penicillin G, ampicillin, or vancomycin) in combination with streptomycin or gentamicin in cases caused by enterococcal strains with high level resistance to streptomycin. A 4-week treatment course may be adequate in many cases. In patients with streptomycin-resistant strains, mitral valve disease, illness of greater than 3 months' duration, and/or relapse after previous therapy, a 6-week treatment course should probably be administered. With standard treatment and the appropriate use of valve replacement, a cure rate of approximately 85% can be expected. PMID- 1617075 TI - Enterococcal infections in surgical patients: the mystery continues. AB - The frequency of isolation of enterococci from surgical patients has increased significantly during the past decade, although the role of these organisms as pathogens in mixed infections remains a mystery. Bacteremia and other infections in which enterococci are the only pathogens frequently result in high morbidity and mortality among patients unless specific antimicrobial therapy is initiated promptly. Debate continues concerning the necessity for treatment with such agents when this organism is isolated as a component of a polymicrobial infecting flora. Our recent data indicate that enterococci are rarely isolated in postoperative infections after penetrating abdominal trauma if no gastrointestinal perforation has occurred. However, they were found in 56% of postoperative infections of patients with gastrointestinal perforation. In contrast, enterococci were isolated in only 9% of cultures of specimens from patients with secondary suppurative peritonitis. The occurrence of superinfection after therapy with a cephalosporin appears to be an important factor in this finding. Future studies are necessary to evaluate the efficacy of antibiotic treatment of enterococcal infections and to assess the need for prophylaxis against enterococci. PMID- 1617076 TI - Antimicrobial resistance in Streptococcus pneumoniae: an overview. AB - Clinical resistance to penicillin in Streptococcus pneumoniae was first reported by researchers in Boston in 1965; subsequently, this phenomenon was reported from Australia (1967) and South Africa (1977). Since these early reports, penicillin resistance has been encountered with increasing frequency in strains of S. pneumoniae from around the world. In South Africa strains resistant to penicillin and chloramphenicol as well as multiresistant strains have been isolated. Similar patterns of resistance have been reported from Spain. Preliminary evidence points to a high prevalence of resistant pneumococci in Hungary, other countries of Eastern Europe, and some countries in other areas of Europe, notably France. In the United States most reports of resistant pneumococci come from Alaska and the South, but resistance is increasing in other states and in Canada. Pneumococcal resistance has also been described in Zambia, Japan, Malaysia, Pakistan, Bangladesh, Chile, and Brazil; information from other African, Asian, and South American countries is not available. The rising prevalence of penicillin resistant pneumococci worldwide mandates selective susceptibility testing and epidemiological investigations during outbreaks. PMID- 1617077 TI - Antimicrobial resistance in Streptococcus pneumoniae: a South African perspective. AB - Resistance to penicillin among South African strains of Streptococcus pneumoniae increased from 4.9% in 1979 to 14.4% in 1990. Except for resistance to co trimoxazole (44%), resistance to other antimicrobial agents remained relatively low. Multiply resistant strains belonged mainly to serovars 6B, 19A, 14, and, more recently, 23F. Use of chloramphenicol to treat meningitis caused by strains relatively resistant to penicillin proved to be unsatisfactory, probably because of the inadequate bactericidal activity of chloramphenicol against these strains. Spread of penicillin-resistant nasopharyngeal strains in pediatric wards was most common among children who received antimicrobial therapy. Penicillin-binding protein (PBP) patterns were shown to vary in resistant clinical strains. Interspecies transfer of penicillin resistance between Streptococcus mitis and S. pneumoniae was demonstrated and antigenic homology was found in PBPs 1A and 2B of strains belonging to these species. Restriction enzyme mapping following DNA amplification of the PBP 2B gene revealed six arrangements among South African strains within serogroup 19. Despite extensive studies in South Africa and several other countries, many questions with regard to the global problem of antimicrobial resistance among S. pneumoniae strains remain unanswered, especially those that relate to prevalence in developing regions of the world. PMID- 1617078 TI - Antimicrobial resistance in Streptococcus pneumoniae: an epidemiological survey in France, 1970-1990. AB - The antimicrobial resistance of Streptococcus pneumoniae was surveyed in 1970 1990 at Saint Joseph and Broussais hospitals in Paris (3,279 isolates) and in 1984-1990 at the National Reference Center for Pneumococci (NRCP) in Creteil (8,128 isolates). All isolates were tested for susceptibility and serotyped. At St. Joseph and Broussais hospitals, the rate of resistance to tetracycline increased from 14% in 1970 to 46.5% in 1978 and then decreased to approximately 20% in 1988-1990. Resistance to chloramphenicol appeared in 1972; its frequency remained at less than 10% until 1990. Resistance to macrolides was first detected in 1976, increased to 20% in 1984, and reached 29% in 1990. Among strains submitted to the NRCP, resistance to penicillin (MIC, greater than or equal to 0.1 mg/L) remained infrequent (less than or equal to 1.1%) between 1984 and 1986 but then increased steadily, reaching 12% in 1990. The frequency of high-level resistance to penicillin (MIC, greater than 1 mg/L) among penicillin-resistant pneumococci increased from 13% in 1988 to 48% in 1990. Compared with other serotypes, the penicillin-resistant serotype isolated most frequently (23F, 49.3%) was more often highly resistant to penicillin and was more often multiresistant. PMID- 1617079 TI - Trends in antimicrobial resistance of clinical isolates of Streptococcus pneumoniae in Bellvitge Hospital, Barcelona, Spain (1979-1990). AB - From January 1979 to December 1990 we studied the susceptibility of 1,492 pneumococcal strains isolated from adult patients in Bellvitge Hospital, Barcelona, Spain, to nine antimicrobial agents. Among clinically significant pneumococci, the incidence of penicillin-resistant strains increased from 4.3% in 1979 to 40% in 1990, and that of erythromycin-resistant strains also rose from 0% in 1979 to 9.4% in 1990. On the other hand, the incidence of strains resistant to tetracycline decreased from 76.1% to 37.6%, as did that of chloramphenicol resistant strains, from 56.5% to 29.4%. The incidence of co-trimoxazole-resistant strains was about 40% throughout the study. Even more alarming was the finding that about 70% of penicillin-resistant strains showed multiple resistance to non beta-lactam antibiotics. All pneumococci were susceptible to vancomycin, and all but six were susceptible to rifampin. We observed that isolates from cerebrospinal fluid and the respiratory tract were significantly more resistant to penicillin than were isolates from blood. The majority of strains (95%) belonged to serogroups or serotypes included in the 23-valent pneumococcal vaccine and 77.6% of penicillin-resistant strains belonged to groups 23, 6, 9, and 19. PMID- 1617080 TI - A nonlinear analysis of pulsatile blood flow applied to investigate shear stress in arterial prostheses. AB - Although the main function of an arterial graft is to restore distal blood flow, there is evidence that certain local parameters of blood flow, particularly wall shear stresses, are important in determining the graft's long-term patency. Wall shear stresses were associated with intimal hyperplasia, intimal proliferation, and endothelial cell development, morphology, and attachment. Here we present a detailed method which permits the investigation of the wall shear stress acting on arteries and prostheses in dogs. The theory takes into account the nonlinear terms of the Navier-Stokes equations as well as the nonlinear behaviour and large deformation of the arterial wall. It is based on the numerical resolution of the nonlinear equations by the Crank-Nicolson method which was selected for its unconditional stability. Through the locally measured values of the pressure, pressure gradient, radius and flow rate, the velocity distribution and wall shear stress at a given location along the artery or the prosthesis, can be determined. Complete results on the same dog are presented for the distal aorta and for the middle of a chemically processed prosthesis, implanted as substitute in the thoracic aorta. PMID- 1617081 TI - Syntheses, interfacial active properties and toxicity of new perfluoroalkylated surfactants. AB - New surfactants have been synthesized with perfluorohexyl-groups as hydrophobic tail, a polyethyleneglycol-methylether as hydrophilic head and a prolongator between them. The prolongator units are -C4H8-, -C2H4OC5H10-, -C2H4OC3H6C(O)- and -CH2CH(OEt)CH2-. The surface tension, CMC and the interfacial tension water/perfluorocarbon were measured and the surface excess concentrations of the surfactant molecules were calculated. The influence of the surfactants on in vitro proliferation of human cell lines Hela and Molt 4 was investigated as a parameter for biocompatibility. The influence of the surfactants led to a reduction of cell proliferation depending on the concentration and chemical nature of the surfactant. Thus the prolongators changed the properties of the surfactants. They reduced the interfacial tension water/perfluorocarbon and improved the biocompatibility of surfactants. PMID- 1617082 TI - Initiation of polymerization with ultrasound in dental composite resin. AB - A single paste composite resin comprising methacrylate monomers, inorganic fillers, activators and an ultrasonic generator assembled by a piezoceramic transducer and a working tip was developed. The resin can polymerize and harden under irradiation with ultrasound having frequencies from 20 to 50 KHz and intensity from 12 to 40 W/cm2. The new technology is promising as a safe and effective method for restoration of tooth defects. PMID- 1617083 TI - Short-term effect of guided bone regeneration and electrical stimulation on bone growth in a surgically modelled resorbed dog mandibular ridge. AB - This study compares the quantitative bone changes that occur in attempting to augment a resorbed mandibular ridge by electrical stimulation and by the guided bone regeneration technique. At the base line three defects resembling an atrophic ridge were created in the mandible of 5 beagle dogs. Concomitantly, a constant current generator producing 20 +/- 2 mA was implanted under the floor of the mouth. Six weeks later a titanium cathode was inserted in the first bony defect and connected to the generator (electrical stimulation = ES); another titanium cathode, not connected to the generator, was inserted in the second defect (non-electrical stimulation = non-ES); the third defect remained without an electrical device (membrane only = MO). All 3 defects were covered with an expanded polytetrafluorethylene membrane, so as to prevent soft tissue proliferation into the defects. Tetracycline bone labelling compounds were administered to mark new bone formation. Four weeks following stimulation, ground sections were prepared for fluorescent microscopy. Differences between ES vs MO and between non-ES vs MO mean scores were statistically significant, indicating that 4 weeks of electrical stimulation resulted in similar bone formation as with non- electrical stimulation when both are confined to a membrane isolated defects. PMID- 1617084 TI - A novel agarose acrobeads protein A column for selective immunoadsorbance of whole blood: performance, specificity and safety. AB - The present study describes the performance and safety parameters of a novel column composed of protein A linked to acrobeads. Hemoperfusion of anticoagulated whole human blood was carried out in a closed system. Specific adsorption of IgG was documented in whole blood, plasma and IgG diluted in saline. Specific activity of the column was 3.52 mg/ml beads. These studies revealed slight changes in platelet counts and minor hemolysis. The relatively short period needed for maximal hemoperfusion effect and safety may enable the use of this novel therapeutic approach in clinical practice. PMID- 1617085 TI - Covalent binding of protamine by glutaraldehyde to bioprosthetic tissue: characterization and anticalcification effect. AB - Calcification is the principal cause of the clinical failure of bioprosthetic heart valves (BHV). The hypothesis of this work was that an impaired balance between positively and negatively charged amino acids, due to the reaction with Lys and Hyl tissue-collagen residues, expose affinity sites to Ca++. We further hypothesized that regardless of the cause(s) of BHV calcification, positive charge modification of the tissue will prevent their propensity to calcify. Modification of BHV tissue was obtained by covalently binding protamine sulfate, a polybasic peptide, via glutaraldehyde. The modification procedure resulted in stable, covalent links of approximately 5.3% w/w protamine with undiminished anticalcification properties, even after long storage. Significant prevention of calcification was exhibited by the p-bound tissue in comparison to BHV tissue, 66.0 and 106.5 micrograms/mg calcium, respectively, after 30 days of subdermal implants in rats. The results support our hypotheses, and orthotopical heart valve replacements are required in order to completely evaluate the treatment efficacy and biocompatibility. PMID- 1617086 TI - Purification and characterization of liposomes encapsulating hemoglobin as potential blood substitutes. AB - In view of the desirability to increase the survival time of the liposome-based artificial red blood cells in vivo, the variables influencing optimum hemoglobin capture and preservation for the bovine hemoglobin-loaded liposomes (LEHb) are investigated. In order to predict the in vivo response, the necessary experiments for the in vitro system characterization have been carried out. The liposomes are prepared by the Reverse Phase Evaporation technique and then purified using a Sepharose 4B column. The purified LEHbs display a unimodal size distribution in the submicron range with a volume average diameter of 0.115 microns and a particle count of 1.25* 10(15) per ml of suspension. Analysis of the lipi/Hb content of the liposomes reveals that the variations in the ratio of Hb encapsulated to lipid entrapped (Hb/L)f as a function of the initial Hb concentration ([Hb]o) is insignificant compared to the net augmentation of (Hb/L)f as a function of the increasing initial lipid to Hb loading ([L]o). Meanwhile high [Hb]o s are necessary for the preservation of oxyhemoglobin. PMID- 1617087 TI - A potential blood substitute from a tetronic polyol and a modified hemoglobin. AB - This investigation reports a new potential blood substitute. An acellular fluid is formed between a Tetronic polyol and a modified hemoglobin. It was possible to stabilize the hemoglobin with glutaric acid. The subsequent reaction with the alcohols of the Tetronic polyol resulted in a useful resuscitative fluid. Exchange transfusion experiments in rats was possible at the 75% replacement level with an excellent survival rate. This was apparently possible because of the effective transport properties of this material. Histological sections of the liver, kidney and lungs showed little or no permanent damage to the organs. The Tetronic polyol - modified hemoglobin complex was not excreted in the urine in contrast to the modified hemoglobin by itself and a solution of unmodified hemoglobin. These preliminary studies indicate that this combination of a polymer and modified hemoglobin has a potential use as a red cell substitute. PMID- 1617088 TI - On the perfluorocarbon emulsions of second generation. AB - For formulation of perfluorocarbon-emulsions (PFC-emulsions) of second generation new perfluorocarbons (F-dimorpholines, F-dipiperidines and F cyclohexylmorpholine) were synthesized, acting both as oxygen carriers and as interfacial active compounds (IFACs). The stabilizing effect of these IFACs is interpreted and a new theory is introduced. Also new classes of fluorosurfactants were synthesized and tested for biocompatibility. In PFC mixtures compounds of the type RFRH (RF = CmF2m + 1, RH = CnH2n + 1) are acting as IFACs but also as anchor-groups for lipophilic surfactants. PMID- 1617089 TI - [Bad times for the coordinators]. PMID- 1617090 TI - [Introduction of computers in health centers and their efficient application to administrative procedures]. PMID- 1617091 TI - [Study of diffuse chronic hepatopathy in the outpatient context]. AB - OBJECTIVE: Description of the general characteristics of patients with Diffuse Chronic Hepatopathy (DCH) in an ABS. DESIGN: Empirical study of a prospective and retrospective type. Site. Primary Care. ABS La Mina. Sant Adria de Besos. PATIENTS AND OTHER PARTICIPANTS: All patients diagnosed as suffering DCH since 1984, in line with histological or clinical--morphological criteria accepted in the literature. MAIN MEASUREMENTS AND RESULTS: Using a data base of the centre's morbidity and mortality register, 287 reports of patients over 14 years old defined as having DCH were examined. 222 cases met the established criteria. Most of these were males (68%), and to an even higher proportion in the group with alcoholic etiology (84%), which was the most common cause of DCH (64.4%). There was a lower number of complications and deaths attributable to DCH than in published hospital series. CONCLUSIONS: Among the characteristics of DCH in a natural population using the health services, it is important to note the predominance of compensated forms having a rate of complications and deaths attributable to DCH significantly lower than what was observed in hospital series. This information may be of use in planning activities at the ABS level. PMID- 1617092 TI - [Morbidity caused by industrial accidents in a health zone]. AB - OBJECTIVE: The aim of the present study is to discover the morbidity produced by workplace accidents among the earning population of Molina de Segura Health Area. DESIGN: This was a descriptive crossover study. Site. The study was carried out in the Primary Care framework, in the Molina de Segura Health Area and with the collaboration of the Labour Health Unit of Insalud-Murcia. PATIENTS AND OTHERS PARTICIPANTS: Over a year a total of 774 cases of time off work due to workplace accidents, out of a total of 9,302 workers, were examined. 679 cases of workers resident in Molina de Segura were included in the study, whose time-off dates fell between July 1, 1989 and June 30, 1990 and where the company for which they worked was based or had its trading name located in Molina. MAIN MEASUREMENTS AND RESULTS: Of the total cases of time off work studied, 539 (79.4%) were men and 140 (20.6%) were women. The pathologies most often found were "blows, bruisings and crushings" (22.8%), "wounds and cuts" (16.8%), "back pain" (10.5%), "strains" (9.4%) and "fractures" (4.5%). A statistically significant association was found between being "a man" and "back pain"; and "a woman" and "sprains". CONCLUSIONS: The predominant pathologies among workplace accidents are of a less serious nature. Some pathologies owing to workplace accidents are mistakenly referred to the health services as ordinary illness. There is insufficient compliance by health professionals with filling in the forms for time off work and return to work. PMID- 1617093 TI - [The P-10 as a tool in the evaluation of the use of a pediatric hospital emergency service by the primary care network]. AB - With the aim of determining if the Primary Care network adequately uses our centre's Emergency service, the 390 P-10s received during May and June 1990 were examined. The presence of clinical judgement, the percentage of admissions, the place of origin of the P-10, the relationship of the issuing centre to our Health Area, the diagnosis made in the Emergency Centre and the patient's destination were all analysed. 42.3% came from rural areas. Clinical judgement was exercised in 56.13%. The P-10s from urban areas showed that clinical judgement had been exercised in 63.6% of cases, as against only 49.7% in the rural areas and 43.2% in the special emergency service. 13.2% were admitted. 41.7% of the referral forms did not come from our health area. The results led us to conclude that there is an insufficient use of the P-10 in our field, as the majority of these patients could have been taken on by the Primary Care network. PMID- 1617094 TI - [Cognitive deterioration and dementias in an urban geriatric population]. AB - OBJECTIVE: To find the extent of cognitive deterioration and dementias and their approximate etiology, in Pamplona's geriatric population. DESIGN: Crossover study. SITE. Pamplona's geriatric population. PATIENTS AND OTHERS PARTICIPANTS: Sample of 393 people over 64, drawn in random fashion from among the population of this age Pamplona. Ordered according to sex and age group. MAIN MEASUREMENTS AND RESULTS: The diagnostic sequence followed for the evaluation of the level of cognitive deterioration was that of Folstein's Minimental test; then the DSM-111 criteria for diagnosing dementia; and the attempt to define dementias by means of the Hachinski scale. Scores lower than 24 were observed in 24.9% of old people, reaching 82.8% in those over 84. Dementia affected 8.9% of people older than 64, and as many as 55.2% of those over 84. The aetiology of these dementias is, according to the Hachinski scale, parenchymatous in 42.8% of cases, mixed or doubtful in another 42.8% and vascular in 14.4%. Both the low educational level of those patients suffering dementia and their serious functional deterioration were notable. CONCLUSIONS: A high level of dementias exists in our elderly population. A big percentage of these are overlooked as concrete clinical phenomena, although their formal diagnosis at the Primary Care stage is relatively simple and extremely useful in order to tackle the earliest and most treatable cases. PMID- 1617095 TI - [Quality assurance of prenatal care in a rural health center]. AB - OBJECTIVE: This study was carried out with the aim of evaluating the quality of Prenatal Care (PNC) and improving attention to the pregnant woman. DESIGN: This was a retrospective evaluation, with a later monitoring of two indicators: an early start to care and an evaluation of risk. Site. The study was undertaken in a rural Primary Care Centre. PATIENTS AND OTHERS PARTICIPANTS: For purposes of the evaluation all the pregnant women (222) looked after between 1988 and 1990 were studied; for the monitoring, all those between July 1990 and June 1991. MAIN MEASUREMENTS AND RESULTS: On the first evaluation, both the starting of PNC within the first 12 weeks (in 65% of cases) and the evaluation of obstetric risk at the first visit (29% compliance) were considered unacceptably low. With the help of corrective measures and simple practical monitoring, 100% compliance was reached in 12 months. The risk evaluation on subsequent visits (between 73 and 95% compliance) and the number of checks (90% compliance) were considered adequate, and no intervention was made. CONCLUSIONS: We concluded that the PNC programmes should include quality assurance activities, as these have a positive effect on the improvement of medical care. PMID- 1617097 TI - [Acute HIV infection]. AB - OBJECTIVE: Primary HIV infection presents a non-specific and polymorphous clinical profile. We present two cases which show how a high level of clinical awareness can lead to an early diagnosis. DESIGN: A retrospective study of all the HIV positive patients treated in Zaragoza's Miguel Servet Hospital between 1985 and 1991 was carried out. Site. The medical records studied concerned the hospital as regards admissions and out-patient consultations. PATIENTS: The two cases which we contributed fulfilled the serologic criteria of acute HIV infection. MAIN MEASUREMENTS AND RESULTS: The man-woman relationship was 1/1. The only way of contagion found was heterosexual. Predominant clinical symptoms were cutaneous-mucous, with a prominent condition of oesophagitis produced by Candida. CONCLUSIONS: A high level of clinical awareness on the part of the Primary Care doctor can contribute significantly to the detection of new cases and controlling the HIV epidemic. PMID- 1617096 TI - [Respiratory manifestations and gastroesophageal reflux]. AB - OBJECTIVE: Presentation of 7 cases of Gastro-oesophageal Reflux (GOR) detected through the respiratory symptomatology which they manifested. DESIGN: Retrospective clinical observations. Site. Primary Care. PATIENTS: Six males (41, 58, 61, 66, 67 and 76 years old) and one woman of 63 were clinically examined on presenting a dry after-dinner cough and a night-time cough. RESULTS: 10% of people suffering GOR present secondary respiratory manifestations. CONCLUSIONS: The importance of its early detection rests on the possibility of avoiding chronic respiratory pathologies such as inherent asthma, pulmonary fibrosis, laryngitis and recurrent pneumonia, occurring as a consequence of GOR. For this reason we consider it vital that this condition in its many forms of manifestation should be recognised in the Primary Care sphere, so that correct diagnosis and treatments can then be proceeded with. PMID- 1617098 TI - [Adolescent medicine (and Part II)]. PMID- 1617100 TI - [Family physician: much more than an able communicator]. PMID- 1617099 TI - [Paradoxes and possibilities of community participation in primary health care (II). Critical and emancipation alternatives]. PMID- 1617101 TI - [Prescriptions of parenteral medication]. PMID- 1617102 TI - [A rare cause of neck tumors. Diagnosis in primary health care]. PMID- 1617103 TI - Translocation of the nuclear autoantigen La to the cell surface of herpes simplex virus type 1 infected cells. AB - Recently we developed a procedure to translocalize one of the extractable nuclear antigens (ENAs), the La protein, to the cell surface of CV-1 cells. Here we report that herpes simplex virus type 1 infection can also induce a translocation of the autoantigen to the cell surface. On the cell surface we detected La protein assembled with large protrusions. Within these protrusions La protein colocalized with virus particles. These protrusions are known to be released from the cell after virus infections. Such complexes consisting of self and virus could provide helper determinants for an anti-self response, and therefore be important in generation of autoimmunity. PMID- 1617104 TI - Experimental autoimmune adrenalitis: a murine model for Addison's disease. AB - Experimental autoimmune adrenalitis was produced in mice by immunizing 8 times or more at intervals of 30 days with syngeneic adrenal extract mixed with Klebsiella O3 lipopolysaccharide (KO3 LPS) as a potent adjuvant. The cortex regions of the adrenal glands after the 8th injection were definitely infiltrated with polymorphonuclear leukocytes (PMN). The main infiltrates in the lesions after the 9th injection were replaced by mononuclear cells, such as small lymphocytes and macrophages, and further by fibrous connective tissues. There were no histological changes in the medullary regions. The repeated immunization developed the delayed type hypersensitivity to adrenal extract and production of anti-adrenocortical autoantibody in those immunized mice. Moreover, the adrenalitis could be produced in normal mice by transfer of spleen cells from hyperimmunized mice, suggesting the critical role of the cell-mediated immunity. This experimental model might be useful to study immunological phenomena in the pathogenesis of Addison's disease. PMID- 1617105 TI - Search for cross-reactive idiotypes on monoclonal and myasthenia gravis acetylcholine receptor antibodies. AB - Myasthenia gravis patients have serum anti-acetylcholine receptor antibodies that compete with monoclonal antibodies for binding to epitopes on the human acetylcholine receptor. To investigate the presence of shared idiotypes we immunised syngeneic mice with each of ten well-characterised monoclonal antibodies, previously raised against purified human acetylcholine receptor, and tested the polyclonal antisera and seven monoclonal anti-idiotype antibodies, for binding to the antigen-combining site, to framework idiotopes, and by ELISA. The polyclonal sera were mostly directed against antigen-combining site idiotopes and cross-reacted only with monoclonal anti-acetylcholine receptor antibodies that bound to the same region on the acetylcholine receptor. In contrast, five of the seven IgM monoclonal anti-idiotypic antibodies raised, none of which demonstrated antigen-combining site specificity in solution, cross-reacted with mAbs binding to more than one region. None of the antisera showing reactivity with the antigen combining site inhibited the binding of MG anti-acetylcholine receptor antibody. PMID- 1617106 TI - Anti-histone reactivity in systemic lupus erythematosus sera: a disease activity index linked to the presence of DNA:anti-DNA immune complexes. AB - This study shows that purified murine monoclonal anti-DNA antibodies and human polyclonal anti-DNA antibodies (from systemic lupus erythematosus--SLE- patients), preincubated with DNA, acquire anti-histone reactivity. Conversely, DNAse I treatment of SLE patients' antibodies with anti-histone activity abolishes such activity. It has previously been demonstrated that anti-DNA antibodies bind to the cell membrane and recognize cell-surface polypeptides that have been identified with histones by partial sequencing. In a series of 33 sera from patients with clinically active disease and 29 sera from patients in clinical remission, positivity of an immunoblot analysis detecting antibodies against these polypeptides was associated with clinical activity of SLE (sensitivity, 0.88; specificity, 0.90). Anti-histone reactivity detected by ELISA appeared to be also a good marker of SLE activity (sensitivity, 0.64; specificity, 0.54). As expected, anti-native DNA antibody positivity and lowered complement dosage were also associated with clinical activity (sensitivity, 0.79 and 0.63, respectively; specificity, 0.48 and 0.93, respectively). Since anti histone reactivity reflects, at least partly, the presence of anti-DNA antibodies complexed to DNA, which could bind to cell-membrane determinants, and is associated with disease clinical activity, it is suggested that this mechanism can contribute to explain the pathogenicity of anti-DNA antibodies. PMID- 1617107 TI - Germ-free condition and the susceptibility of BALB/c mice to post-thymectomy autoimmune gastritis. PMID- 1617108 TI - HLA class II genes in Graves' disease. AB - Inheritance of Graves' disease has been linked to the HA-DR3 gene product which may function in some specific way in antigen presentation. To determine whether the first extracellular domain of this protein, which is specifically involved in antigen presentation, has the same sequence in patients with Graves' disease and in normal individuals, we have amplified the second exon using the polymerase chain reaction, and then cloned and sequenced the DNA segment. In eight subjects with Graves' disease, sequences identical to prototypic reported sequence for DRB1*0301 were recovered, and in two individuals sequences varied by a few nucleotides, leading to 1-3 amino acid substitutions which did not occur in a pattern. Sequences identical to the prototypic sequence known as DRB3*0101, also previously known as DRw52, were also recovered. Thus the HLA-DRB1 and B3 genes present in patients with autoimmune disease appear to be the same as those present in the general population. These observations indicate that a unique allele is not present in patients with autoimmune disease, but rather that the normal DR3 allele itself, in a manner yet to be described, increases the probability of developing autoimmune thyroid disease. PMID- 1617109 TI - Adoptive transfer of the gld syndrome in double congenic nude lpr mice. AB - Homozygosity for either the lymphoproliferation (lpr) or the generalized lymphoproliferative disease (gld) mutation of mice causes the development of strikingly similar autoimmune and lymphoproliferative syndromes. The relationship between the lpr and gld mutations was studied by grafting B6 gld spleen cells (SC) to athymic B6 nude lpr mice (B6 nulpr) or to B6 nude (B6 nu) mice as controls. The injection of B6 gld SC, but not of B6 wild SC, to B6 nulpr mice caused a prolongation of survival of the short living B6 nulpr recipients. This was associated with elevated anti-single stranded DNA antibody titers and a serum hyperglobulinemia, as well as by a splenomegaly which was nearly as high as in genetically B6 gld mice, and by a marked lymphadenopathy (though milder than that of B6 gld mice). In contrast the [gld----nu] chimaeras showed a more attenuated form of gld-induced syndrome. These results suggest that the lpr environment supplied in athymic lpr recipients is compatible with--and may even favour--the development of the gld-induced syndrome. PMID- 1617110 TI - Cloning of a human autoimmune response: preparation and sequencing of a human anti-thyroglobulin autoantibody using a combinatorial approach. AB - Thyroid lymphocyte RNA from a Hashimoto patient exhibiting high titre serum IgG autoantibodies against thyroglobulin (Tg) has been used to construct a Fab library in phage lambda. Screening of this library with radioiodinated Tg has permitted the cloning of an anti-Tg antibody (MH52) with an affinity of 4.5 x 10(9) molar-1 as determined by inhibition ELISA. Sequence analysis showed MH52 to be an authentic antibody of the IgG1/K isotype with variable region genes from the VHI and VKIII families in combination with the JH3, DK4 and JK2 gene segments. The MH52 light chain gene showed high sequence homology (93%) with the germline gene used by several rheumatoid factors and some DNA autoantibodies. Greater divergence from the germline was observed in the case of the MH52 heavy chain gene which showed 86% homology with a germline heavy chain gene isolated from human liver. Overall the similarity between the genes coding for MH52 and the genes coding for some other autoantibodies of non-related specificity might suggest that similar regulatory processes control the formation of these different autoantibodies. PMID- 1617111 TI - 1,25-Dihydroxyvitamin D3 attenuates the expression of experimental murine lupus of MRL/l mice. AB - The murine strain MRL/l spontaneously develops a systemic lupus erythematosus (SLE)-like syndrome. An increased number of T cells and polyclonal T helper cell activity has been described in these mice suggesting a potential role for 1,25 dihydroxyvitamin-D3 [1,25-D3], an antiproliferative hormone selecting the T helper lymphocyte subset. One month old MRL/l mice were submitted or not to 1,25 D3 0.1 microgram for 4 weeks, then 0.15 microgram given i.p. every other day for 18 weeks while maintained on a low calcium chow. Dermatologic lesions, i.e. alopecia, necrosis of the ear and scab formation, were completely inhibited by 1,25-D3 therapy. By 20 weeks, all mice had developed proteinuria. However, the degree of proteinuria was somewhat reduced in treated mice as assessed by urine protein/creatine ratios (less than 4 vs greater than 4 in treated vs untreated mice respectively). Moreover, a trend for a reduction in serum titers for anti ssDNA antibodies was observed at 18 weeks. The active vitamin D metabolite had no effect on the development of the generalized lymphoid hyperplasia. Hypercalcemia developed when 1,25-D3 was increased to 0.15 microgram (2.62 +/- 0.12 vs 1.97 +/- 0.07 mmol/l, treated vs untreated mice respectively). These results suggest a beneficial role of 1,25-D3 in the prevention or attenuation of some manifestations of murine SLE, a model sharing many immunologic features with human SLE. PMID- 1617112 TI - Refractory immune hemolytic anemia with a high thermal amplitude, low affinity IgG anti-Pra cold autoantibody. AB - A 54 y.o. woman presented with acute Coombs-negative hemolytic anemia at an outside hospital where she received 25 RBC transfusions and did not respond to prednisone or splenectomy. On transfer to our hospital, routine DAT and IAT were weakly positive, occasionally negative. When a modified "cold" antiglobulin test was employed, the result was strongly positive for IgG, weakly positive for C3d. Cold agglutinin titer was 32, and the Donath-Landsteiner test was negative. The autoantibody exhibited Pra specificity. The patient failed IV-IgG, high dose IV pulse steroids and cyclophosphamide, and continued to require daily transfusions. She responded 21 days after receiving daily plasma exchange (x3), with pulse cyclophosphamide on the third day, followed by escalating daily oral cyclophosphamide. PMID- 1617113 TI - Histological characteristics of lupus nephritis in F1 mice with chronic graft versus-host reaction across MHC class II difference. AB - Renal lesions at the chronic phase of MHC class-II-disparate graft-versus-host reaction (GVHR) were examined. To induce GVHR, C57BL/6 (B6) spleen cells were injected twice into either (B6 x bm12)F1 (class-II-disparate), (B6 x bm1)F1 (class-I-disparate) or (bm1 x bm12)F1 mice (class-I + II-disparate). For comparison, (C57BL/10 x DBA/2)F1 (BDF1) mice injected with DBA/2 spleen cells were also used. (B6 x bm12)F1 and BDF1 recipients showed marked elevation of anti DNA antibodies, circulating immune complexes (CIC) and the number of immunoglobulin producing cells (IgPC). At 20 weeks after cell injection, severe immune complex glomerulonephritis (ICGN) was observed in (B6 x bm12)F1 recipients, but was far less severe in (bm1 x bm12)F1 recipients and was not observed in (B6 x bm1)F1 recipients. ICGN was also observed in BDF1 recipients at 12 weeks after cell injection. By immunofluorescent microscopy, IC deposition was detected along the capillary loops and also in the mesangial area in (B6 x bm12)F1 recipients, while BDF1 recipients showed only a capillary pattern. By light microscopy, the renal lesion of (B6 x bm12)F1 recipients appeared similar to those of BDF1 recipients. Histologically, (B6 x bm12)F1 recipients serve as a good model for lupus glomerulonephritis induced by class-II-disparate GVHR. PMID- 1617114 TI - Tissue specific binding of lymphocytes to the thyroid gland of BB/W rats may be an early event in the development of thyroiditis. AB - Thyroiditis occurs in about 50% of diabetic Bio Breeding/Worcester (BB/W) rats. In order to investigate the earliest stages of lymphocyte homing to the thyroid gland in the development of experimental autoimmune thyroiditis, we measured the amount of trapping of peripheral blood lymphocytes (PBL) from BB/W rats to the thyroid gland of syngeneic recipient animals. PBL, from donor normal or diabetic BB/W rats, labelled with 51Cr, were injected, i.v., into normal, "potentially diabetic" or diabetic BB/W recipients. After 24 hr the rats were sacrificed and the radioactivity of selected individual organs counted. Results were calculated as % binding of 51Cr-labelled PBL/unit weight of tissue and expressed as a binding index by comparing to binding to recipient blood lymphocytes. A significant binding index was taken as greater than 1.0. PBL from diabetic or normal donor BB/W rats were shown to bind significantly to the thyroid gland of 8 out of 19 "potentially diabetic" or diabetic recipient syngeneic rats, but to none of the normal (non diabetic) recipients tested. Sixty percent of "potentially diabetic" BB/W rats and 50% of diabetic rats at 3-4 months of age showed a significant level of binding of donor lymphocytes from syngeneic diabetic or normal animals to their thyroid gland, while, at 5-6 months the proportion of recipient rats giving positive tests was much less (17%). The source of the donor lymphocytes (diabetic, or normal) did not significantly influence the binding. Lymphocyte binding to pancreas was not significantly greater than to control tissues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617115 TI - Quantitative and functional analyses of spleen and in situ islet immune cells before and after diabetes onset in the NOD mouse. AB - Cytofluorometric analysis using specific monoclonal antibodies directed against the T cell antigens Thy-1.2, CD4, CD8, CD4V beta(8.1 + 8.2 + 8.3), and the antigen Mac-1 expressed by mature macrophages and NK cells were used to characterize and quantify the phenotypes of (1) unfractionated and Percoll gradient fractionated in situ islet immune cells isolated from prediabetic and diabetic female NOD mouse spleens. We found in prediabetic female mice that the majority (approximately 70%) of the in situ islet immune cells were Thy-1.2 positive T cells. CD4 positive T cells (approximately 40%) were the most abundant phenotype together with double negative T cells (approximately 20%). The percentage of CD8 positive T cells were approximately 10%, and only approximately 4% of the immune cells were Mac-1 positive. The percentages of CD4V beta (8.1 + 8.2 + 8.3) positive and double negative T cells in diabetic spleens were significantly higher in comparison to prediabetic spleens. In C57B1/6J control nondiabetic mice the percentage of double negative T cells in the spleens was significantly 4-fold lower when compared to diabetic NOD spleens. The specific cytolytic activity mediated by in situ islet immune cells against 51Cr-labeled dispersed syngeneic single-cell islet cells at an effector to target ratio of 20 was twenty- to thirty-fold higher than that mediated by prediabetic splenic lymphoid cells. It is concluded that prediabetic NOD mouse in situ islet immune cells are mostly CD4 positive and double negative T cells, and that CD4 and CD8 positive T cells in the intra-islet infiltrate warrants further evaluation as potential effector T cells in target beta-cell destruction. PMID- 1617116 TI - Occupational cancer mortality among urban women in the former USSR. AB - Occupational cancer mortality was evaluated among approximately three million female pensioners from urban areas of the former USSR. In 1970, these women experienced 14,918 cancer deaths. Occupational data were obtained from death certificates and the 1970 USSR National Population Census. Thirty-five occupational groups, including nine predominantly professional or office-work groups and 26 groups involving physical labor, were evaluated. The expected mortality rates were based on the urban female population of the USSR in 1970. Data for all cancer sites combined, and cancers of the esophagus, stomach, colon, rectum, lung, breast, cervix, and hematopoietic system are presented. Among all female pensioners, there were significant increases of all cancers combined (rate ratio [RR] = 1.05), and cancers of the breast (RR = 1.3), cervix (RR = 1.3), and the hematopoietic system (RR = 1.2), and a significant deficit of cancer of the esophagus (RR = 0.8). Many well-established associations between cancer and occupation among men were observed among the study group of female pensioners, such as stomach and lung cancer among miners, and hematopoietic malignancies among scientists and physicians. Other associations, to be investigated further, also were observed, such as excess lung cancer among waitresses. The peak employment period for this cohort of women was during World War II and the postwar period, when Soviet women outnumbered men almost two-to-one. Consequently, many of the women held jobs that are typically held by men. Thus, this study provides valuable information on occupational risks to women that may be relevant in other countries where women increasingly are being employed in jobs traditionally held by men. PMID- 1617117 TI - Diuretics may increase risk of renal cell carcinoma. AB - The risk for kidney cancer was examined in a Danish cohort of 192,133 people on a hospital discharge register who had been given a diagnosis of hypertension, heart failure, or edema, and were presumed to be probable users of diuretics. The subjects were identified from 1977 to 1987 and followed-up for cancer through 1987. A total of 10,630 cancers was observed. While the risk for all cancers was increased slightly (standard mortality ratio [SMR] = 122, 95 percent confidence interval [CI] = 120-124), the risk for renal cell carcinoma was more than doubled (SMR(men) = 221, CI = 192-253; SMR(women) = 246, CI = 213-283). Increased risks were found in all age groups, and, although surveillance bias was present initially, the risk increased consistently in the years following discharge. Risk estimates for individuals discharged with hypertension were similar to those for the total cohort. Use of diuretics was validated in a random sample of 100 individuals. More than 70 percent were taking diuretics at the time of discharge. The increased risk for renal cell carcinoma in this cohort may indicate either that diuretics are involved in the etiology of renal cell carcinoma or that the risk can be attributed to confounders, including smoking, which affect risk for both the discharge diagnosis and renal cell carcinoma. PMID- 1617118 TI - Risk factors for breast cancer by age and menopausal status: a case-control study in Singapore. AB - A case-control study was conducted among Singapore Chinese women, comprised of 200 histologically confirmed cases of breast cancer and 420 hospital controls. Subjects were interviewed on family history of breast cancer, social and demographic characteristics, reproductive history, and diet one year prior to interview. Differences in risk factors were observed according to menopausal status. In the premenopausal group, the most consistently significant nondietary effect was an increased risk with late age at first birth. In postmenopausal women, the most consistent nondietary effects were increased risks with nulliparity, tall stature, high educational status, and a family history of breast cancer. In premenopausal women, the strongest dietary effects were low risks with high intakes of polyunsaturated fatty acids (PUFA), beta-carotene, soya protein as a proportion of all protein, and a high risk with high red-meat intake. No dietary effects were observed in postmenopausal women. Examination of effects by 10-year age groups suggested that the differences in the effects of age at first birth, nulliparity, height, education, beta-carotene intake, and PUFA intake between premenopausal and postmenopausal women were at least partly attributable to age-related differences in the baseline distributions of these variables. The variation in the effects of red meat and soya protein appeared to be attributable mainly to menopausal status itself, which is consistent with the hypothesis that these factors operate on risk by way of hormonal mechanisms. PMID- 1617119 TI - Risk factors for kidney cancer in New South Wales, Australia. II. Urologic disease, hypertension, obesity, and hormonal factors. AB - In a population-based case-control study of kidney cancer in New South Wales, Australia, data from structured interviews with 489 cases of renal cell cancer (RCC) and 147 cases of renal pelvic cancer (CaRP) diagnosed in 1989 and 1990, and 523 controls from the electoral rolls, confirmed the link between obesity and RCC. In addition, regular consumption of 'diet' pills independently increased the risk for this cancer. A diagnosis of hypertension at least two years before interview raised the risk for RCC, and regular use of beta-blockers, a class of antihypertensive drug, independently increased the risk for RCC and CaRP (risk ratio = 1.5-1.8). No independent effect was found for use of diuretics. Additional information provided by this study includes increased risks associated with kidney injury (RCC, CaRP)--possibly attributed to recall bias--and kidney infection (CaRP), as well as a nonsignificantly raised risk linked with kidney stones (RCC, CaRP) and a significantly reduced risk for RCC in persons giving a history of lower urinary tract infection. No significant association of RCC was found with hormonal factors (age at menarche or menopause; child-bearing; regular use of oral contraceptives or estrogens; hysterectomy or oophorectomy). PMID- 1617120 TI - Herpes simplex virus type 2 infection and cervical cancer: a prospective study of 12 years of follow-up in Finland. AB - This study was initiated to investigate the role of past herpes simplex virus type 2 (HSV-2) infection, as determined by serum antibody analysis, in the etiology of cervical neoplasia. Two Finnish registers, the registry of the Social Insurance Institution's Mobile Clinic Survey and the Finnish Cancer Registry, were linked. About 40,000 blood samples were drawn in 1968-72 and stored by the Social Insurance Institution. According to the Cancer Registry, 32 cases of cervical carcinoma or carcinoma in situ for which serum samples were available were diagnosed in this cohort during a follow-up of 12 years (1968-81). The serum samples of these individuals and age matched controls (2:1) from the cohort were analyzed for HSV-2 antibodies. HSV-2 infection as determined by the best available HSV-2 type-specific antibody assay, glycoprotein gG2-ELISA, was not related to cervical neoplasia, i.e., the risk of cervical neoplasia among the HSV 2 positive women was not higher than that among the negative ones (smoking adjusted relative risk = 0.5, 95 percent confidence interval = 0.2-1.6). The results do not support the hypothesis that HSV-2 is an etiologic agent for cervical neoplasia. PMID- 1617121 TI - Case-control study of risk factors for cervical neoplasia in Denmark. II. Role of sexual activity, reproductive factors, and venereal infections. AB - Sexual, reproductive and venereal risk factors for cervical neoplasia were investigated in a population-based case-control study of 586 women with histologically verified, cervical squamous-cell carcinoma in situ, and 59 women with invasive squamous-cell cervical cancer, diagnosed from 1985 to 1986 in Copenhagen. Cases were identified from the computerized Danish Cancer Registry. An age-stratified control group (n = 614) was drawn at random from the female population in the study area by means of the Danish Central Population Register. A structured questionnaire was mailed to cases as well as controls. Increasing number of sexual partners exerted a significant effect on the risk both for carcinoma in situ, and invasive cancer, independently of age at first intercourse and other potential confounders. Conversely, the association with early age at first intercourse became statistically insignificant after allowance for other risk factors, although an increasing risk was still observed with decreasing age at sexual debut. Early age at first episode with genital warts was a significant risk factor for carcinoma in situ, perhaps indicating a possible increased susceptibility of the cervix epithelium during adolescence. A history of genital warts was a good predictor of risk for carcinoma in situ, whereas a history of previous gonorrhea was associated with an increased risk for invasive carcinoma. Women with multiple births had a significantly increased adjusted risk, especially for carcinoma in situ, although some association was also observed with invasive cervical cancer. The study supports the hypothesis of cervical neoplasia being a sexually transmitted disease, and that carcinoma in situ and invasive cervical carcinoma, to a high degree, have similar patterns of risk factors. PMID- 1617122 TI - Obesity in youth and middle age and risk of colorectal cancer in men. AB - To investigate an association between colon cancer and obesity during early adulthood--a potentially important period in the etiology of this disease--the authors assembled, by computer linkage, a population-based historical cohort of 52,539 men born between 1913 and 1927 residing in Hawaii (USA), for whom weight and height had been recorded in 1942-43 and 1972. Linkage of this cohort to the Hawaii Tumor Registry resulted in the identification of 737 incident cases of colorectal cancer for 1972-86. An average of 3.8 cancer-free controls were matched to each case on month and year of birth and ethnicity of the parents. A case-control analysis in each anatomic subsite of the large bowel revealed that both early and middle-age body mass increased the risk of sigmoid cancer in men in a dose-dependent fashion. The odds ratios (OR) for sigmoid cancer for the highest compared with the lowest tertiles of Quetelet index were: 2.1 (95 percent confidence interval [CI] = 1.4-3.2) and 1.7 (CI = 1.1-2.5), at ages 15-29 and in prediagnostic years, respectively. These associations were additive and independent of socioeconomic status. Men who were above the median Quetelet index in 1942 and 1972 had an OR of 2.7 (CI = 1.8-4.0), compared with those who were below the median in both periods. This study provides further evidence for an association of obesity with colon cancer in men and suggests that this association is limited to the sigmoid colon and may be related to both early and late events of colon carcinogenesis. PMID- 1617123 TI - Reproductive factors, exogenous female hormones, and colorectal cancer by subsite. AB - The associations between reproductive factors, exogenous hormones, and colorectal cancer were examined among female subjects in a population-based case-control study in Sweden. The study was performed in Stockholm in 1986-88, and included 299 cases and 276 controls. There was little evidence that age at first birth, number of months of breast feeding, age at menarche, or age at menopause influenced the risk of colon or rectal cancer. However, the results indicate that postmenopausal hormone-replacement therapy might reduce the risk of colorectal cancer (age-adjusted relative risk [RR] = 0.4, 95 percent confidence interval [CI] = 0.2-0.9). Compared with nulliparous women, women with at least four births were at reduced risk for colon cancer (RR = 0.5, CI = 0.2-1.2) but not rectal cancer (RR = 1.0, CI = 0.4-2.6). However, no trend across increasing parity was observed. Adjustments for diet, body mass, and physical activity had little influence on the results. PMID- 1617125 TI - Soft tissue sarcoma and tobacco use: data from a prospective cohort study of United States veterans. AB - A report of an increased risk of soft tissue sarcoma (STS) among users of smokeless tobacco led us to evaluate this association and the role of other types of tobacco in a prospective cohort mortality-study of United States veterans. A total of 248,046 veterans provided tobacco-use histories on a mail questionnaire in 1954 or 1957. Data on subsequent tobacco use were not collected. By 1980, 119 deaths from STS had occurred among the cohort members. Veterans who had ever chewed tobacco or used snuff had a nonsignificant 40 percent excess of STS (95 percent confidence interval [CI] = 0.8-2.6; 21 deaths) in comparison with veterans who had never used any tobacco products. Risk was limited to former users (relative risk [RR] = 1.5) with no excess seen among current users (RR = 0.9). Frequent former users had higher risk (RR = 1.9) than infrequent users (RR = 1.3). Risk was slightly higher in persons who started using smokeless tobacco at younger ages, but did not increase with duration of use or with late age at cessation of use. Most veterans who used chewing tobacco or snuff also used some other form of tobacco. No STS deaths occurred among the 2,308 veterans who used smokeless tobacco only. An unexpected finding of the study was the significant excess of STS deaths among cigarette smokers (RR = 1.8, CI = 1.1-2.9). Risk was higher among ex-smokers (RR = 2.2) than among current smokers (RR = 1.5) and was not related to number of cigarettes per day, age started smoking, duration, or pack-years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617124 TI - Alcohol consumption and lung cancer in white males. AB - Experimental and epidemiologic investigations in alcoholic and nonalcoholic populations have suggested a role of alcohol in lung carcinogenesis. The association between alcohol consumption and lung cancer was investigated among 280 White males with histologically confirmed, primary lung cancer and 564 White male controls, participants in the Western New York Diet Study (United States). Among heavy smokers (over 40 pack-years), total alcohol consumption was associated with an increased risk of lung cancer with adjustment for age, years of education, pack-years of cigarette smoking, and intake of carotenoids and fat. In this group, the odds ratio for drinkers of more than 24 drinks per month was 1.6 compared with those who drank less. Drinkers of more than 12 beers per month were 1.6 times more likely to develop lung cancer than nondrinkers of beer after controlling for age, years of education, and cigarette smoking (95 percent confidence interval = 1.0-2.4, P for trend = 0.003). Occupational and dietary factors did not seem to explain these findings. Although cigarette smoking is the major cause of lung cancer, the role of alcohol, independent or in interaction with cigarette smoking, deserves further investigation. PMID- 1617126 TI - Low incidence of familial breast cancer among Hispanic women. AB - There is a paucity of data on familial patterns of breast cancer among minority populations. This study compared the frequency of cancer in 1,095 first-degree relatives of 50 White, 46 Black, and 49 Hispanic breast-cancer patients referred to The University of Texas M.D. Anderson Cancer Center (United States). Family histories of cancer were derived from a self-administered questionnaire on risk factors. Expected numbers of cancers were calculated from the Connecticut Tumor Registry for White and Black relatives and from the New Mexico Tumor Registry for Hispanic relatives. Family history of a first-degree relative with breast cancer was the most important risk factor for both Black and White patients. Significantly elevated standardized incidence ratios (SIR) for breast cancer were noted among White (SIR = 4.5, 95 percent confidence interval [CI] = 1.2-11.4) and Black (SIR = 4.1, CI = 1.1-10.4) relatives younger than age 45. Despite the small number of Black patients, the combined effect of family history of breast cancer and the relative's age at diagnosis (under 45 years) was associated with an SIR of 7.1 (CI = 1.9-18.1). A deficit of cancer was noted in Hispanic women; only one patient reported having a first-degree relative with breast cancer. These findings, although based on small numbers, suggest that Hispanics have a lower rate of familial breast cancer than Whites and Blacks, and that they may possess protective factors that reduce their risk for breast cancer. PMID- 1617127 TI - Neonatal exposure to protoporphyrin-activating lighting as a contributing cause of childhood acute lymphocytic leukemia. AB - While being a relatively rare disease, acute lymphocytic leukemia (ALL) is the leading form of cancer in children in the developed world today. ALL sharply peaks in incidence at ages three to four years. In the United States there have been persistent, unexplained increases in incidence of ALL in the past two decades. We hypothesize that exposure to photosensitizing lighting immediately after birth may be a contributing cause of ALL. Fluorescent lamps and other light sources with strong illumination, around 400 nanometers, are protoporphyrin activating. Activation of protoporphyrin produces superoxides and free radicals that can induce breaks in DNA. In newborn nurseries in the US, the intensity of lighting has increased five- to 10-fold over the past two decades. Thus, protoporphyrin-activating light may be a contributing cause of childhood ALL. Additional retrospective and prospective studies should be undertaken of the relationship between exposure of newborns to protoporphyrin-activating illumination and the development of childhood ALL, along with in vitro studies of the hematologic effects of fluorescent lighting. Protoporphyrin-activating lighting is clearly not the sole determinant of ALL, but it could be a completely preventable cause. Inexpensive plastic filters could reduce these exposures substantially. PMID- 1617128 TI - Predominance of hospital deliveries among children with acute lymphocytic leukemia: speculations about neonatal exposure to fluorescent light. PMID- 1617129 TI - Smoking and multiple myeloma. PMID- 1617130 TI - Leukemia clusters around nuclear facilities in Britain. PMID- 1617131 TI - Leukemia clusters around nuclear facilities in Britain. PMID- 1617132 TI - United States--Australia workshop on membrane biophysics. PMID- 1617133 TI - Enhancement of carotenoid-to-chlorophyll singlet energy transfer by carotenoid carotenoid interaction. AB - The apparent quantum yield of singlet-singlet spirilloxanthin-to bacteriochlorophyll a energy transfer increases linearly with the residual spirilloxanthin content in Rhodospirillum rubrum membrane vesicles from which this carotenoid has been partially removed. Since it has been previously shown that carotenoid-carotenoid interaction is a linear function of the residual spirilloxanthin level in the major pigment-protein complex of those vesicles (Zurdo, J., R. M. Lozano, C. Fernandez-Cabrera, and J. M. Ramirez. 1991. Biochem. J. 274:881-884), it appears that such degenerate interaction enhances singlet energy transfer. Part of the enhancement may be explained if the energy donor is the spirilloxanthin 1Bu----1Ag (S2----S0) transition, because exciton coupling probably brings its energy closer to that of the Qx (S2----S0) transition of bacteriochlorophyll. In contrast, it seems that the possible stabilization of the spirilloxanthin 2Ag (S1) state would hardly improve energy transfer, because this hidden state probably lies below the S1 bacteriochlorophyll state. In any case, the stabilizing effects of carotenoid-carotenoid interactions seem insufficient to explain the enhancement of energy transfer. Direct or indirect effects of carotenoid dimerization on the three-dimensional structure of the pigment cluster appear to be required to account for such enhancement. PMID- 1617134 TI - Cytoplasmic hydrogen ion diffusion coefficient. AB - The apparent cytoplasmic proton diffusion coefficient was measured using pH electrodes and samples of cytoplasm extracted from the giant neuron of a marine invertebrate. By suddenly changing the pH at one surface of the sample and recording the relaxation of pH within the sample, an apparent diffusion coefficient of 1.4 +/- 0.5 x 10(-6) cm2/s (N = 7) was measured in the acidic or neutral range of pH (6.0-7.2). This value is approximately 5x lower than the diffusion coefficient of the mobile pH buffers (approximately 8 x 10(-6) cm2/s) and approximately 68x lower than the diffusion coefficient of the hydronium ion (93 x 10(-6) cm2/s). A mobile pH buffer (approximately 15% of the buffering power) and an immobile buffer (approximately 85% of the buffering power) could quantitatively account for the results at acidic or neutral pH. At alkaline pH (8.2-8.6), the apparent proton diffusion coefficient increased to 4.1 +/- 0.8 x 10(-6) cm2/s (N = 7). This larger diffusion coefficient at alkaline pH could be explained quantitatively by the enhanced buffering power of the mobile amino acids. Under the conditions of these experiments, it is unlikely that hydroxide movement influences the apparent hydrogen ion diffusion coefficient. PMID- 1617135 TI - The invertebrate myosin filament: subfilament arrangement of the solid filaments of insect flight muscles. AB - Transverse sections (approximately 140 nm thick) of solid myosin filaments of the flight muscles of the fleshfly, Phormia terrae-novae, the honey bee, Apis mellifica, and the waterbug, Lethocerus uhleri, were photographed in a JEM model 200A electron microscope at 200 kV. The images were digitized and computer processed by rotational filtering. In each of these filaments it was found that the symmetry of the core and the wall was not the same. The power spectra of the images showed sixfold symmetry for the wall and threefold symmetry for the core of the filaments. The images of the filaments in each muscle were superimposed according to the sixfold center of the wall. These averaged images for all three muscles showed six pairs of subunits in the wall similar to those found in the wall of tubular filaments. From serial sections of the fleshfly filaments, we conclude that the subunits in the wall of the filaments represent subfilaments essentially parallel to the long axis of the filament. In each muscle there are additional subunits in the core, closely related to the subunits in the wall. Evaluation of serial sections through fleshfly filaments suggests that the relationship of the three subunits observed in the core to those in the wall varies along the length of the filaments. In waterbug filaments there are three dense and three less dense subunits for a total of six all closely related to the wall. Bee filaments have three subunits related to the wall and three subunits located eccentrically in the core of the filaments. The presence of core subunits can be related to the paramyosin content of the filaments. PMID- 1617136 TI - The myosin filament XIV backbone structure. AB - The substructure of the thick filaments of chemically skinned chicken pectoralis muscle was investigated by electron microscopy. Images of transverse sections of the myosin filaments were determined to have threefold symmetry by cross correlation analysis, which gives an unbiased determination of the rotational symmetry of the images. Resolution, using the phase residual test (Frank et al. 1981. Science [Wash. DC]. 214:1353-1355), was found to be between 3.2 and 3.6 nm. Three arrangements of nine subfilaments in the backbone were found in all regions of the filament at ionic strengths of 20 and 200 mM. In the average images of two of these, there were three dense central subfilaments and three pairs of subfilaments on the surface of the thick filament. In the average image of the third arrangement, all of the protein mass of the nine subfilaments was on the surface of the filament with three of them showing less variation in position than the others. A fourth arrangement appearing to be transitional between two of these was seen often at 200 mM ionic strength and only rarely at 20 mM. On average, the myosin subfilaments were parallel to the long axis of the filament. The different arrangements of subfilaments appear to be randomly distributed among the filaments in a transverse section of the A-band. Relative rotational orientations with respect to the hexagonal filament lattice, using the three densest subfilaments as reference showed a major clustering (32%) of filaments within one 10 degrees spread, a lesser clustering (15%) at 90 degrees to the first, and the remainder scattered thinly over the rest of the 120 degrees range. There was no obvious pattern of distribution of the two predominant orientations that could define a superlattice in the filament lattice. PMID- 1617137 TI - Replication of viruses in a growing plaque: a reaction-diffusion model. AB - An understanding of the viral replication process commonly referred to as "plaque growth" is developed in the context of a reaction-diffusion model. The interactions among three components: the virus, the healthy host, and the infected host are represented using rates of viral adsorption and desorption to the cell surface, replication and release by host lysis, and diffusion. The solution to the full model reveals a maximum in the dependence of the velocity of viral propagation on its equilibrium adsorption constant, suggesting that conditions can be chosen where viruses which adsorb poorly to their hosts will replicate faster in plaques than those which adsorb well. Analytic expressions for the propagation velocity as a function of the kinetic and diffusion parameters are presented for the limiting cases of equilibrated adsorption, slow adsorption, fast adsorption, and large virus yields. Hindered diffusion at high host concentrations must be included for quantitative agreement with experimental data. PMID- 1617138 TI - Kinetics and mechanism of cell membrane electrofusion. AB - A new quantitative approach to study cell membrane electrofusion has been developed. Erythrocyte ghosts were brought into close contact using dielectrophoresis and then treated with one square or even exponentially decaying fusogenic pulse. Individual fusion events were followed by lateral diffusion of the fluorescent lipid analogue 1,1'-dihexadecyl-3,3,3',3' tetramethylindocarbocyanine perchlorate (Dil) from originally labeled to unlabeled adjacent ghosts. It was found that ghost fusion can be described as a first-order rate process with corresponding rate constants; a true fusion rate constant, k(f), for the square waveform pulse and an effective fusion rate constant, k(ef), for the exponential pulse. Compared with the fusion yield, the fusion rate constants are more fundamental characteristics of the fusion process and have implications for its mechanisms. Values of k(f) for rabbit and human erythrocyte ghosts were obtained at different electric field strength and temperatures. Arrhenius k(f) plots revealed that the activation energy of ghost electrofusion is in the range of 6-10 kT. Measurements were also made with the rabbit erythrocyte ghosts exposed to 42 degrees C for 10 min (to disrupt the spectrin network) or 0.1-1.0 mM uranyl acetate (to stabilize the bilayer lipid matrix of membranes). A correlation between the dependence of the fusion and previously published pore-formation rate constants for all experimental conditions suggests that the cell membrane electrofusion process involve pores formed during reversible electrical breakdown. A statistical analysis of fusion products (a) further supports the idea that electrofusion is a stochastic process and (b) shows that the probability of ghost electrofusion is independent of the presence of Dil as a label as well as the number of fused ghosts. PMID- 1617139 TI - Potentiostatic deposition of DNA for scanning probe microscopy. AB - We describe a procedure for reversible adsorption of DNA onto a gold electrode maintained under potential control. The adsorbate can be imaged by scanning probe microscopy in situ. Quantitative control of a molecular adsorbate for microscopy is now possible. We found a potential window (between 0 and 180 mV versus a silver wire quasi reference) over which a gold (111) surface under phosphate buffer is positively charged, but is not covered with a dense adsorbate. When DNA is present in these conditions, molecules adsorb onto the electrode and remain stable under repeated scanning with a scanning tunneling microscope (STM). They become removed when the surface is brought to a negative charge. When operated at tunnel currents below approximately 0.4 nA, the STM yields a resolution of approximately 1 nm, which is better than can be obtained with atomic force microscopy (AFM) at present. We illustrate this procedure by imaging a series of DNA molecules made by ligating a 21 base-pair oligonucleotide. We observed the expected series of fragment lengths but small fragments are adsorbed preferentially. PMID- 1617140 TI - Phospholipid interactions in model membrane systems. I. Experiments on monolayers. AB - We study the lateral headgroup interactions among phosphatidylcholine (PC) molecules and among phosphatidylethanolamine (PE) molecules in monolayers and extend our previous models. In this paper, we present an extensive set of pressure-area isotherms and surface potential experiments on monolayers of phospholipids ranging from 14 to 22 carbons in length at the n-heptane/water interface, over a wide range of temperature, salt concentration, and pH on the acid side. The pressure data presented here are a considerable extension of previous data (1) to higher surface densities, comprehensively checked for monolayer loss, and include new data on PE molecules. We explore surface densities ranging from extremely low to intermediate, near to the main phase transition, in which range the surface pressures and potentials are found to be independent of the chain length. Thus, these data bear directly on the headgroup interactions. These interactions are observed to be independent of ionic strength. PC and PE molecules differ strongly in two respects: (a) the lateral repulsion among PC molecules is much stronger than for PE, and (b) the lateral repulsion among PC molecules increases strongly with temperature whereas PE interactions are almost independent of temperature. Similarly, the surface potential for PC is found to increase with temperature whereas for PE it does not. In this and the following paper we show that these data from dilute to semidilute monolayers are consistent with a theoretical model that predicts that, independent of coverage, for PC the P-N+ dipole is oriented slightly into the oil phase because of the hydrophobicity of the methyl groups, increasingly so with temperature, whereas for PE the P-N+ dipole is directed into the water phase. PMID- 1617142 TI - Computer models of a new deoxy-sickle cell hemoglobin fiber based on x-ray diffraction data. AB - A new x-ray fiber diffraction pattern from deoxygenated sickle cell erythrocytes has been observed. It displays 14 layer lines with a 109 A periodicity compared with the 64 A periodicity of the "classic" sickle cell hemoglobin (HbS) fiber. These data and association energy calculations serve as a basis for computer model building. Systematic searches over four-dimensional parameter space yielded twelve protofilament models that satisfy the following constraints: (a) two HbS molecules be related by twofold screw symmetry with a translational repeat of 109 A; (b) at least one of the substituted residues in HbS, val beta 6, should participate in intermolecular contacts; and (c) the energy of intermolecular interaction be less than -24 kcal/mol. Each of the protofilament models is a zigzag mono-strand that stands in contrast to the double-stranded protofilament of the "classic" fiber. Fiber models were constructed with each of the 12 protofilament models, pseudo-hexagonally packed. Searches of variable packing parameters showed four fiber models with minimal protofilament association energies and minimal differences between calculated transforms and observed data. The R-factor was less than 0.24 for each of these four models. In three of the fiber models the protofilament association energy is between -(93 and 130) kcal, and in a fourth, the energy is -64 kcal. One protofilament model constituted three distinct fiber models of the lower energy class, and a second protofilament model packed with a higher association energy into a fourth fiber model. The selection of a unique fiber model from among these four cannot be made because of the limited available data. Fibers models constructed with any of the ten other protofilament models do not satisfy the conditions of minimal association energy and R-factor. PMID- 1617141 TI - Phospholipid interactions in model membrane systems. II. Theory. AB - We describe statistical thermodynamic theory for the lateral interactions among phospholipid head groups in monolayers and bilayers. Extensive monolayer experiments show that at low surface densities, PC head groups have strong lateral repulsions which increase considerably with temperature, whereas PE interactions are much weaker and have no significant temperature dependence (see the preceding paper). In previous work, we showed that the second virial coefficients for these interactions can be explained by: (a) steric repulsions among the head groups, and (b) a tilting of the P-N+ dipole of PC so that the N+ end enters the oil phase, to an extent that increases with temperature. It was also predicted that PE interactions should be weaker and less temperature dependent because the N+ terminal of the PE head-group is hydrophilic, hence, it is tilted into the water phase, so dipolar contributions among PE's are negligible due to the high dielectric constant of water. In the present work, we broaden the theory to treat phospholipid interactions up to higher lateral surface densities. We generalize the Hill interfacial virial expansion to account for dipoles and to include the third virial term. We show that to account for the large third virial coefficients for both PC and PE requires that the short range lateral attractions among the head groups also be taken into account. In addition, the third virial coefficient includes fluctuating head group dipoles, computed by Monte Carlo integration assuming pairwise additivity of the instantaneous pair potentials. We find that because the dipole fluctuations are correlated, the average triplet interactions do not equal the sum of the average dipole pair potentials. This is important for predicting, the magnitude and the independence of temperature of the third virial coefficients for PC. The consistency of the theory with data of both the second and the third virial coefficients extends the applicability of the head-group model to semiconcentrated monolayers, in agreement with the surface potential data in the foregoing paper. PMID- 1617143 TI - Consideration of dipole orientation angles yields accurate rate equations for energy transfer in the rapid diffusion limit. AB - Dipole-dipole energy transfer between suitable donor and acceptor chromophores is an important luminescence quenching mechanism and has been shown to be useful for distance determination at the molecular level. In the rapid diffusion limit, where the excited-state lifetime of the donor is long enough to allow the donor and acceptor to diffuse many times their average separation before deexcitation, it is usually assumed that the relative dipolar orientation is completely averaged due to rotational Brownian motion. Under this simplifying assumption, analytical expressions have been derived earlier for the energy transfer rate between donor and acceptor characterized by different geometries. Most such expressions, however, are only approximate because complete angular averaging is permitted only in a geometry that possesses spherical symmetry surrounding each chromophore. In this paper analytical expressions that correctly account for incomplete angle averaging due to steric hindrance are presented for several geometries. Each of the equations reveals a dependence of the energy transfer rate on chromophore orientation. It is shown that correctly accounting for this effect can lead to improvements in estimates of the distance of closest approach from measured quenching rates based on energy transfer experiments. PMID- 1617144 TI - Analytical sedimentation studies of turkey gizzard myosin light chain kinase and telokin. AB - Sedimentation equilibrium and velocity studies were performed with turkey gizzard myosin light chain kinase (MLCK) and telokin, a small protein apparently corresponding to the sequence of the COOH-terminal end of MLCK. The measurements carried out with MLCK give values for the monomer molecular weight (M(r)), sedimentation coefficient (S20 degrees,w), and virial coefficient (A2) of 108,000, 3.74 S, and -1.95 x 10(-4) mol.ml.g-2, respectively. In the case of telokin, M(r) = 18,500; S20 degrees, w = 1.63 S; and A2 = 5.81 x 10(-4)mol.ml.g 2. Combination of the results of the two kinds of experiment shows that MLCK is a rod-shaped molecule (a/b = 18.9) with a Stoke's radius of 69 A. Telokin is also elongated (a/b = 8.3) with a Stoke's radius of 29 A. MLCK apparently exhibits self-association, with 15% of the protein sedimenting as a dimer in the experiments. PMID- 1617145 TI - A sensitive measure of surface stress in the resting neutrophil. AB - The simplest parameterized model of the "passive" or "resting receptive" neutrophil views the cell as being composed of an outer cortex surrounding an essentially liquid-like highly viscous cytoplasm. This cortex has been measured to maintain a small persistent tension of approximately 0.035 dyn/cm (Evans and Yeung. 1989. Biophys. J. 56:151-160) and is responsible for recovering the spherical shape of the cell after large deformation. The origin of the cortical tension is at present unknown, but speculations are that it may be an active process related to the sensitivity of a given cell to external stimulation and the "passive-active" transition. In order to characterize further this feature of the neutrophil we have used a new micropipet manipulation method to give a sensitive measure of the surface stress as a function of the surface area dilation of the highly ruffled cellular membrane. In the experiment, a single cell is driven down a tapered pipet in a series equilibrium deformation positions. Each equilibrium position represents a balance between the stress in the membrane and the pressure drop across the cell. For most cells that seemed to be "passive," as judged by their spherical appearance and lack of pseudopod activity, area dilations of approximately 30% were accompanied by only a small increase in the membrane tension, indicative of a very small apparent elastic area expansion modulus (approximately 0.04 dyn/cm). Extrapolations back to zero area dilation gave a value for the tension in the resting membrane of 0.024 +/- 0.003 dyn/cm, in close agreement with earlier measures. A few cells showed virtually no change in cortical tension and fit the persistent cortical tension model of Evans and Yeung (1989. Biophys. J. 56:151-160). However, other cells that also appeared "passive," as judged by their spherical appearance, had membrane tensions that increased as the apparent surface area was increased. Thus, the postulated,persistent "cortical tension" does not appear to be a unique and constant parameter for all cells as the membrane area is dilated.This measurement of membrane tension could represent a sensitive indication of the first stages of cell activation and the"passive-active" transition. PMID- 1617146 TI - Anti-insulin antibody structure and conformation. II. Molecular dynamics with explicit solvent. AB - Molecular dynamics at 300 K was used as a conformation searching tool to analyze a knowledge-based structure prediction of an anti-insulin antibody. Solvation effects were modeled by packing water molecules around the antigen binding loops. Some loops underwent backbone and side-chain conformational changes during the 95 ps equilibration, and most of these new, lower potential energy conformations were stable during the subsequent 200-ps simulation. Alterations to the model include changes in the intraloop, main-chain hydrogen bonding network of loop H3, and adjustments of Tyr and Lys side chains of H3 induced by hydrogen bonding to water molecules. The structures observed during molecular dynamics support the conclusion of the previous paper that hydrogen bonding will play the dominant role in antibody-insulin recognition. Determination of the structure of the antibody by x-ray crystallography is currently being pursued to provide an experimental test of these results. The simulation appears to improve the model, but longer simulations at higher temperatures should be performed. PMID- 1617147 TI - Pair distribution functions in small systems: implications for protein structure analysis. AB - A general formula is derived for the relation between the pair correlation function and the histogram of interparticle distances in small nonuniform systems. The formula is applied to random packings of spheres in a spherical container, which are generated by a Monte Carlo method. When measured properly, the resultant correlation functions are very similar to ones in bulk systems with the same volume fraction of particles. In contrast, the density is very nonuniform as a function of distance from the center of the container. The variation is an order of magnitude for the number density of particle centers, or severalfold for the occupied volume fraction. It is described how these results can be used to analyze the forces that determine protein structure. PMID- 1617149 TI - Conformational analysis of a dinucleotide photodimer with the aid of the genetic algorithm. AB - The solution structure of the photodimer cis,syn-dUp[]dT is derived with the aid of the genetic algorithm. The conformational space available for the molecule is sampled efficiently using the computer program DENISE and tested against a set of constraints available from nmr experiments. The dominant conformation in solution found with this approach can be described by the following combinations of sugar phosphate backbone torsion angles: epsilon(t), zeta(t), alpha(+), beta(-ac), and gamma(t). The conformation of the sugars and glycosidic torsion angles are S type and syn, respectively. The cyclobutane ring and pyrimidines are puckered. In addition, other conformations that exist in equilibrium with the first are found. It is concluded that the cyclobutane-pyrimidine system is rigid, whereas the sugar-phosphate backbone is flexible. The solution structures are compared with the crystal structure of the strongly related cyano-ethyl ester of cis,syn dTp[]dT. PMID- 1617148 TI - Development of an extended simulated annealing method: application to the modeling of complementary determining regions of immunoglobulins. AB - An extended simulated annealing process (ESAP) has been developed in order to obtain an ensemble of conformations of a peptide segment from a protein fluctuating at a given temperature. The annealing process was performed with a fast Monte Carlo method using the scaled collective variables developed by Noguti and Go. The system was divided into two parts: one consists of one or more peptide segments and is flexible around the main-chain and side-chain torsional angles; the other represents the rest of the molecule and was maintained fixed at the atomic positions determined by x-ray experiments. The target function included the nonbonding atomic interactions and a distance function to anchor the N and C terminal ends of each segment to the fixed part. Three systems of complementary determining regions (CDR) of antibodies were tested and compared to x-ray data: L2 loop (7 residues) of the light chain of lambda-type Bence-Jones protein, H1 and the H2 loops (14 residues) of McPC603, and H1 and H2 loops (12 residues) of HyHEL-5. Each state of CDR conformations was characterized at room temperature by the average of their coordinates (average conformation) and the internal energy. With a limited number of annealing processes (10), starting from the extended conformation, we have obtained states with conformations close to the observed x-ray structures, from 1.1 to 1.7 A root mean square deviation (rmsd) of main-chain atoms depending on the system. These states were identical or within 0.25 A rmsd of those of lowest internal energy. For unknown CDR structures the criteria of lowest internal energies from ESAP can be used to predict hypervariable loop structures in antibodies with an accuracy comparable to other methods. PMID- 1617150 TI - Quantum yield for preferential photodimerization in long pyrimidine tracts. AB - The quantum yield for cyclobutyl-pyrimidine dimerization in DNA has been observed to increase approximately linearly with increasing pyrimidine tract length. A model without adjustable parameters for this yield is proposed based on energy delocalization, vibronic symmetry switching, and saturation statistics that describe the average number of (base pairwise) breathing modes in a given tract of pyrimidines. This average number of modes is an approximately linear function of the tract length. Monte Carlo techniques are used to simulate base sequences and photochemical events, and indicate that this model is consistent with experiment for Tetrahymena pyriformis DNA. PMID- 1617151 TI - Conformational preferences of oligopeptides rich in alpha-aminoisobutyric acid. II. A model for the 3(10)/alpha-helix transition with composition and sequence sensitivity. AB - The analysis of the factors that control the helical folding of Aib-rich peptides is extended to include sensitivity to sequence patterns, and in particular the presence of contiguous non-Aib alpha-mono-alkylated residues. The distinct hydrogen-bonding network of the 3(10)-helix, as contrasted with that of the competing alpha-helical structure, is explicitly incorporated into a theoretical model for the 3(10)-helix/alpha-helix equilibrium constant for a given peptide. Finite length effects and the "extra" intrahelical hydrogen bond of the 3(10) form are expressed naturally as a result of this loop analysis. This semiempirical model captures all the established features of existing empirical rules for helical conformational transitions in Aib-rich sequences, as well as the recently detected helical transition induced solely by sequence permutation. PMID- 1617152 TI - The interaction of auramine O with calmodulin: location of the binding site on the connecting strand. AB - The cationic dye auramine O forms a fluorescent complex with Ca(2+)-liganded calmodulin. One moderately strong binding site is present, as well as one or more weaker sites. The binding site for auramine O is different from those for toluidinyl-naphthalene sulfonate. The dependence of binding upon electrolyte concentration suggests a substantial electrostatic component of the free energy of binding. The splitting of the bond between residues 77 and 78 by trypsin digestion abolishes auramine O binding; the N- and C-terminal half-molecules have virtually no binding capacity. This suggests that the primary binding site is located near the midpoint of the connecting strand and includes elements of both half-molecules. Thrombin digestion, which splits calmodulin between residues 106 and 107, also substantially reduces auramine O binding; this may be interpreted in terms of the stabilization of the structure of the connecting strand by interaction with residues within binding domain IV. The binding affinity at pH 5.0, where the helical organization of the connecting strand may be intact, is greater than at neutral pH. PMID- 1617153 TI - Conformation and charge distribution of bicyclic beta-lactams: structure-activity relationships. AB - The structures of 7-oxo-1-azabicyclo[3.2.0]heptane and its 4-oxa, 3-ethylene-4 oxa, and 3-ethylene-6-methyl-4-oxa derivatives, and of 8-oxo-1 azabicyclo[4.2.0]octane and its 5-oxa derivative, were studied by ab initio methods. Conformations were refined without constraints using the 4-21G and the 4 21G* basis sets, and energies and charge distributions were improved by single point 6-31G*/4-21G* calculations. The results are are interpreted in terms of structural trends related to beta-lactamase inhibitor capability. PMID- 1617154 TI - The role of cytokines in the pathogenesis of inflammatory eye disease. AB - A coherent view of the role of cytokines in inflammatory eye disease is emerging as a result of studies both in man and experimental animals. Cytokines have been demonstrated in ocular tissue obtained from patients with intraocular inflammation (uveitis) (gamma interferon, IL-2) and have been shown to induce inflammation in experimental animals after intraocular injection [(IL-1, IL-6, IL 8, tumour necrosis factor (TNF), granulocyte macrophage-colony stimulating factor (GM-CSF)]. Several unique features of the immunology of the eye such as the immunosuppression associated with anterior chamber associated immune deviation (ACAID) may be due to the effects of cytokines. Similarly, common complications of ocular inflammation such as glaucoma, keratic precipitates, retinal (macular) oedema and neovascularization may be mediated by cytokines. Understanding of the role of cytokines in inflammatory eye disease has the potential to lead to the development of therapies to abrogate the effects of these important mediators of the inflammatory response. PMID- 1617155 TI - Rat gro/melanoma growth-stimulating activity. Assessment of the structure responsible for chemotactic activity by use of its fragments prepared by proteolysis and chemical synthesis. AB - Rat gro/melanoma growth-stimulating activity is a dimer composed of two identical subunits. Each subunit consists of 72 amino-acid residues and contains two disulfide bridges. In order to obtain information on the structure responsible for chemotactic activity, various fragments of gro were prepared and tested for their ability to induce chemotaxis. None of the fragments corresponding to residues 1-6, 1-21, 12-31, 36-50 or 52-72 was active as a chemoattractant. Reduced and carboxymethylated gro as well as the tryptic peptide consisting of three peptides, residues 9-21, 28-45 were and 49-61, linked by two disulfide bonds Cys-9-Cys-35 and Cys-11-Cys-51, were inactive. Also, these, peptides did not inhibit the chemotactic activity of gro. Rat gro lacking the N-terminal 6 residues had a reduced activity and the one lacking the C-terminal Lys was as active as intact gro. Therefore, an almost entire portion of the molecule including disulfide cross-links is required for chemotactic activity. PMID- 1617156 TI - CD69 is expressed on Daudi cells in response to interferon-alpha. AB - An approach to obtain monoclonal antibodies directed against cell surface proteins induced by interferon has been developed in order to characterize such proteins and determine their role. Hybridomas obtained by fusion of murine myeloma cells and spleen cells of mice immunized with interferon-alpha-treated Daudi cells were screened for the production of antibodies reacting differentially with interferon-alpha-treated and untreated Daudi cells. One such hybridoma, 2D5, produced an antibody reacting with a 28/32 kDa homodimeric protein (p28/32) expressed at the surface of Daudi cells in response to IFN-alpha treatment. IFN-alpha treatment also increased the basal level of p28/32 detected on peripheral blood leukocytes (PBL). 2D5 Antibody was used to probe the expression of p28/32 on different cells and in response to various inducers. It appears that 2D5 reacted in fact with CD69, a marker of leukocyte activation and that, following IFN-alpha treatment, CD69 was not induced on all cultured cell lines tested. Interestingly, IFN-gamma was also able to induce CD69 expression on a restricted number of cell lines but the induction pattern only partially overlapped that of IFN-alpha. As expected, activation of cells with phorbol myristate acetate (PMA) resulted in a notable increase in the level of CD69 on all cell lines considered except for the epithelial and fibroblastic types. PMID- 1617157 TI - Enhancement of interleukin 6 cytostatic effect on human breast carcinoma cells by soluble IL-6 receptor from urine and reversion by monoclonal antibody. AB - Interleukin 6 receptor soluble urinary protein (IL-6-R-SUP), a purified urinary protein binding IL-6 and identified as a truncated 50 kDa soluble form of the 80 kDa IL-6 cellular receptor, was tested for its biological activity. Addition of IL-6-R-SUP enhances the growth stimulation of mouse plasmacytoma T1165 by subliminal concentrations of human recombinant IL-6. Since this effect could be due to a lower affinity of human IL-6 for the mouse cell receptor, we tested the effect of IL-6-R-SUP on human cells. We show that the growth-inhibitory effect of IL-6 on breast carcinoma cells is enhanced by addition of IL-6-R-SUP to these human cells although they possess abundant IL-6 receptors. With IL-6-R-SUP, complete growth inhibition by IL-6 could be achieved and the cells became more sensitive to low levels of IL-6. These effects were prevented by a monoclonal antibody against IL-6-R-SUP which blocks IL-6 binding to cells. The naturally occurring IL-6-R-SUP may help to increase the growth-regulatory action of IL-6. PMID- 1617158 TI - Effect of major surgery on the release of interferon gamma by peripheral blood mononuclear cells: an investigation at the single cell level using the reverse haemolytic plaque assay. AB - The release of interferon gamma (IFN-gamma) by peripheral blood mononuclear cells from patients undergoing abdominal aortic aneurysm repair was measured using the reverse haemolytic plaque assay. The plasma of these patients was also assayed for interferon gamma using enzyme-linked immunosorbent assay (ELISA). Peripheral blood mononuclear cells from the surgical patients released significantly more IFN-gamma by 9 hours after incision than that released prior to surgery (P less than 0.001). This change persisted up to 9 days after surgery. Plasma IFN-gamma was not detectable using either of two different ELISA techniques. The increased secretion of IFN-gamma by peripheral blood mononuclear cells following major surgery may be a beneficial component of the host's immune response to injury. PMID- 1617159 TI - Biological and structural properties of MIP-1 alpha expressed in yeast. AB - The murine macrophage inflammatory proteins-1 alpha (MIP-1 alpha) and MIP-1 beta are distinct but closely related cytokines. Partially purified mixtures of the two proteins affect neutrophil function and cause local inflammation and fever. The particular properties of MIP-1 alpha have not been well studied, although it has been identified as being identical to an inhibitor of haemopoietic stem cell growth. We have expressed MIP-1 alpha in yeast cells and purified it to sequence homogeneity. Structural analysis of this biologically active material by circular dichroism and fluorescence spectroscopy confirms that MIP-1 alpha has a very similar secondary and tertiary structure to platelet factor 4 and interleukin 8 with which it shares limited sequence homology. The in-vitro stem cell inhibitory properties have been confirmed using a range of murine progenitor cells including purified bone marrow progenitor cells (FACS-1), the FDCP-mix A4 cell line, and spleen colony forming unit (CFU-S) populations. Plateau levels of inhibition of stem cell growth were achieved using concentrations of 0.15 micrograms/ml MIP-1 alpha. We have also demonstrated that MIP-1 alpha is active in vivo: 5 micrograms of MIP-1 alpha per mouse given as a bolus injection, protects stem cells from subsequent in-vitro killing by tritiated thymidine. MIP-1 alpha was also shown to enhance the proliferation of more committed progenitor granulocyte macrophage colony forming cells (GM-CFC) in response to granulocyte macrophage-colony stimulating factor (GM-CSF). PMID- 1617160 TI - Immunocytochemical staining of serous effusions with the monoclonal antibody Ber EP4. AB - Cytospin preparations were made from 102 serous effusions for immunocytochemical staining using a panel of monoclonal antibodies including a new monoclonal antibody Ber-EP4. On cytological examination, 32 fluids were reported to contain tumour cells consistent with metastatic adenocarcinoma; 66 contained benign cells only and three were reported to contain cells suspicious of malignancy. One effusion contained tumour cells consistent with malignant mesothelioma. Positive staining of the tumour cells with Ber-EP4 was observed in the 32 effusions (100%) which contained adenocarcinoma cells. No staining of the mesothelial cells in these 32 specimens was observed. Carcinoembryonic antigen, epithelial membrane antigen Ca2 and CD15 staining of tumour cells was noted in 53%, 50%, 50% and 9% of these cases, respectively. None of the mesothelial cells in the benign effusions stained with Ber-EP4. Nor did the malignant mesothelial cells in the only case of malignant mesothelioma. These findings suggest that Ber-EP4 is a valuable addition to antibodies available for the differential diagnosis of mesothelial cells and adenocarcinoma cells in serous effusions. PMID- 1617161 TI - Renal transplant aspiration cytology. Role for simple morphological criteria. AB - Fine-needle aspiration (FNA) is a well-recognized technique for sampling solid organs. It is used in renal transplantation to clarify the cause of a poorly functioning graft. Differential scoring techniques with respect to peripheral blood cell populations, and immunocytochemistry have been employed in this context. We describe the use of simple morphological criteria alone in renal transplant FNA. We compare these with needle biopsy and clinical parameters and show their value in the detection of active cellular rejection. Their limitations are discussed within the framework of other patterns of transplant pathology. PMID- 1617162 TI - Fine-needle aspiration cytology in a case of chordoma. AB - We report a case of sacrococcygeal chordoma initially diagnosed by fine-needle aspiration cytology. The value of awareness by cytopathologists of the histology of soft tissue tumours is emphasized. PMID- 1617163 TI - An audit of cervical cancer deaths in Nottingham. AB - Death certificates were reviewed and 57 women were identified whose primary cause of death was cervical cancer. Their cervical smear records were reviewed from laboratory files. Only nine had participated in the cervical cancer screening programme before the diagnosis of cervical cancer was made. One woman had an abnormal smear as a result of cervical screening but failed to attend for follow up. The problem of false negative smears is also addressed and the value of review of negative smears for the purposes of cytology audit is emphasized. PMID- 1617164 TI - Significance of borderline nuclear abnormality in cervical smears. AB - Women with cervical smears showing borderline nuclear abnormality (BNA), or reactive changes in the form of squamous metaplasia (SM) or endocervical cell hyperplasia (ECH), were age-matched with healthy controls to determine the outcome of these conditions. No significant difference in the risk of dyskaryosis was observed in cases showing reactive changes and the controls. In contrast, there was a 23% excess of cases showing dyskaryosis in the repeat smears of cases of BNA over the controls. An odds ratio of 8.3 was obtained, showing dyskaryosis in subsequent smears after a diagnosis of BNA. PMID- 1617165 TI - Silver binding nucleolar organizer regions in adrenocortical neoplasia. AB - The possible contribution of the silver colloid technique for staining nucleolar organizer regions in the distinction between benign and malignant adrenocortical neoplasms was investigated. Nine cases of adenoma, eight cases of carcinoma, nine cases of hyperplasia and four normal adrenal cortex specimens were examined. The mean silver binding nucleolar organizer region (Ag-NOR) value in adenoma was 4.29, and in carcinoma 7.16 (P less than 0.001). Adenomas with diameters greater than 3 cm had significantly higher Ag-NOR counts than smaller adenomas. For normal cortex, the mean Ag-NOR value was 2.05 and in hyperplasia, 3.62. The results indicate that the Ag-NOR technique can help in differential diagnosis between benign and malignant adrenocortical lesions and thus may have a prognostic value. PMID- 1617166 TI - Immunity and immunopathology in dengue virus infections. AB - Dengue virus infections are a serious public health problem in tropical and subtropical areas of the world. Based on epidemiological data, it has been postulated that immune responses to dengue virus contribute to the pathogenesis of severe dengue illness, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Host immune responses are also important for controlling dengue virus infection. Therefore, dengue virus infections are an interesting model to explore the interactions between viruses and the immune system which result in immunopathology or recovery from infection. In this paper, we review immune responses to dengue viruses with an emphasis on the human T cell responses, and discuss possible roles of these immune responses in the control of dengue virus infection and in the pathogenesis of DHF/DSS. PMID- 1617167 TI - Viral antigen presentation and MHC assembly. AB - Viruses and other intracellular pathogens represent a unique challenge to the vertebrate immune system. To deal with this problem of intracellular invasion the immune system has developed an elegant strategy to mark virally infected cells. This review discusses current issues relating to the cell biology of MHC molecule assembly and antigen presentation events from the standpoint of viruses and anti viral immunity. PMID- 1617168 TI - [Cortical necrosis of the transplanted kidney. MR tomographic confirmation of the diagnosis?]. AB - Cortical necrosis is a rare complication of renal transplants, which requires urgent diagnosis and management to avoid unnecessary immunosuppression. Seven renal transplants with suspected cortical necrosis were evaluated by Doppler-US, 99mTc-DTPA-perfusion study and Gd-DTPA-enhanced dynamic MRI. In four transplants, cortical necrosis was confirmed by angiography and histology. In diagnosing cortical necrosis with preserved medullary perfusion (n = 2) dynamic MRI was superior to the other modalities. Totally necrotic renal transplants (n = 2) were reliably diagnosed by all imaging methods. PMID- 1617169 TI - [Pseudo-stenosis of the renal artery: a possible defect of color Doppler sonography]. AB - The diagnostic value of pulsed Doppler sonography for the detection of renal artery stenosis was questioned by recent studies. Until now, the diagnostic value of colour-coded Doppler sonography of the renal arteries is not clearly defined in relation to pulsed Doppler. This study deals with specific problems of colour coded Doppler sonography in the examination of the renal arteries. Because of basic technical principles of colour-coded Doppler sonography a stenosis can be imitated especially at the origin of the right renal artery by using a ventral approach to the vessel. This pseudo-stenosis is due to a change of colour similar to an aliasing-phenomenon in a curved vessel. In order to avoid false positive results, a laterodorsal approach to the vessel should be applied additionally. A spectral waveform should be also registered routinely. PMID- 1617170 TI - [A renal function analysis using computed tomography. CT clearance versus 131I hippuran clearance]. AB - The CT clearance in a number of urological patients (39 patients, 25 with normal renal function) was studied by means of an "area under curve" (AUC) method, using a region of interest. 31 patients were given meglumine ioxithalamate and 8 patients Iopamidol as a contrast medium. Both for total and partial function there was highly significant correlation with isotope clearance with good reproducibility. The difference in the pharmacokinetics of the contrast media affected the absolute clearance values. PMID- 1617171 TI - [Pharmacokinetics of gadolinium-DTPA in chronic renal insufficiency requiring dialysis]. AB - MRT with gadolinium-DTPA (0.1 mmol/kg body weight) was performed in 10 patients with renal insufficiency requiring dialysis and the clearance of gadolinium-DTPA was studied. After 3 dialysis on 3 successive days more than 97% of the initial concentration of gadolinium-DTPA had been eliminated. Average half-life was 1.87 hours. There were no side effects in any of the patients. Close laboratory observation of liver function showed no significant changes during the period of study. No contra-indication for the use of this contrast medium in patients with renal insufficiency requiring dialysis was found during this study. PMID- 1617172 TI - [MR tomography in testicular processes. The significance of Gd-DTPA enhanced sequences in comparison with plain T2-weighted sequences]. AB - The value of T1-weighted sequences after intravenous administration of Gd-DTPA and of T2-weighted sequences was compared in 43 patients suspected of having scrotal abnormalities. T2-weighted sequences gave better demonstration of the tunica albuginea and better contrast between tumor and parenchyma. The two techniques were equally sensitive for demonstrating testicular tumors but orchitis was better demonstrated on the contrast enhanced sequences. Motion artifacts were less marked in the T1-weighted sequences with contrast enhancement. In selected cases, contrast enhancement may be a valuable addition to native protocols. Our experience has indicated that MRI provides specific findings in cases of orchitis which are clinically atypical; this facilitates the decision to conservative treatment and prevents unnecessary exploration of the testes. PMID- 1617173 TI - [Catheter embolization of the solitary pulmonary arteriovenous aneurysm]. AB - Catheter embolization with coils was performed as a method of treatment in 3 patients with solitary pulmonary arteriovenous aneurysms (PAVA). This led to permanent occlusion of the PAVA in all cases. There were no complications following embolization. Bearing in mind that other workers also achieved good results by this method, embolization of a solitary PAVA by coils should be preferred to balloon embolization. Surgical treatment should only be carried out for a malformation which is not accessible to embolization or as part of a more complex procedure. PMID- 1617174 TI - [MR venography in deep venous thromboses of the leg and pelvis. A comparison of 2D single layer images and 3D MIP reconstructions with phlebography]. AB - A total of 22 MR venograms were performed in 7 volunteers and 15 patients suspected of deep vein thrombosis of the lower limb and pelvis. MR findings were compared to conventional venography in all patients. MR venography is a reliable method for the exclusion of thrombosis proximal to the popliteal vein. In the calf veins, diagnosis of thrombosis is not yet reliable. For MR venography 2D time-of-flight-inflow-technique and secondary 3D-MIP reconstructions were used and compared to each other. With both methods there were no false negative results in comparison to conventional venography. 2D single slice MR venography showed two false positive results in iliac and one in popliteal vein. MIP 3D reconstructions led to seven false positive results (three iliac, two femoral, two popliteal). The exclusive interpretation of MIP-3D reconstruction is not reliable for decision-making in deep venous thrombosis. PMID- 1617175 TI - [MR tomography of injuries of the medial collateral ligaments of the knee joint]. AB - Frequency and characteristics of lesions of the medial collateral ligaments (MCL) were studied by MRI in 155 patients with trauma to the knee. There were abnormalities of the MCL in 38% of cases with ligamentous injuries and in 27% these were combined with meniscal tears. 11% of these patients showed isolated rupture of MCL and as a result of the MRI findings were treated conservatively. By means of T2*-weighted images the individual lesions could be accurately localised. Characteristic findings have been defined. PMID- 1617176 TI - [The femoropatellar gliding motion during active knee stretching. Imaging using motion-triggered MR tomography]. AB - By means of motion-triggered MRT it has been possible for the first time to demonstrate movements in the patello-femoral joint by means of MRT. Patello femoral movement was studied during active extension of the knee between 30 degrees flexion and complete extension. The knees of 5 normal females and 7 normal males were studied together with 2 women with recurrent lateral patellar luxation. In normal women there was an average 16 degrees (10 to 18 degrees), in men an average of 12 degrees (10 to 14 degrees) of lateralisation of the patella during complete extension of the knee. In 1 patient there was 10 degrees medial displacement of the patella before extension. In 2 knees with recurrent lateral subluxation there was a 20 and 24 degrees displacement of the patella. PMID- 1617177 TI - [Optimization of filtration and lighting parameters in pictures of the hand using digital luminescence radiography]. AB - The appearance of digital radiographs were markedly influenced by post processing. To optimise images of the hand, radiographs of 7 patients with arthritis were modified by various filters. 6 observers evaluated the presence or absence of erosive changes during an ROC study and the advantages of low filtration were demonstrated. Further images were prepared of anatomical preparations in which para-articular defects had been made and of a hand phantom covered in perforated plexiglass. Limited filtration and low enhancement factors again provided the best results. Dose reduction of 50% resulted in a significant deterioration in the ability to recognise erosions and artificial lesions. PMID- 1617178 TI - [The diagnosis of bone marrow lesions in the MR tomogram in children with diseases of the hematopoietic system with special reference to post-therapy changes]. AB - 119 MR-examinations of both tibiae, knees and the lower part of both femur were performed in 41 children suffering from bone marrow disease (27 ALL, 4 AML, 3 NHL, 1 agranulocytosis, 6 anaemia). T1- and T2-spin-echo sequences and a T2 gradient-echo sequence were used. Bone marrow changes in leukaemia were diffuse before therapy and patchy after therapy. Due to their different signal in T2 weighted images, differentiation of the post-therapeutic patchy findings into infiltrations, fibrosis, necrosis and siderosis seems to be possible. In future, MRI will be the method of choice for screening and controlling bone marrow disease if the examination time is shortened by using only a T1-spin-echo sequence and a T2-gradient-echo sequence. PMID- 1617179 TI - [MR mammography in patients at risk]. AB - Dynamic MR mammography (MRM) has high sensitivity for the demonstration of carcinomas. 63 carcinomas were examined by this technique and all showed a signal increase of more than 90% 60 seconds after the injection of 0.1 mmol/kg Gd-DTPA and an almost constant signal intensity (carcinoma plateau) for a further 7 minutes. These characteristic changes applied only to active tumour areas and not to necrotic or fibrotic tumour regions. A possible explanation is the altered vascular architecture due to the growth of malignant tumours. In the presence of a suspect mammogram a carcinoma can be excluded with a high degree of certainty in the absence of contrast enhancement. Signal enhancement in 54 histologically proven cases of non-proliferative mastopathy and in 52 cases of proliferative mastopathy could be reliably distinguished from carcinomas (p less than 0.001). In rare cases of proliferative mastopathy the signal changes were suspicious of a carcinoma. Normal signal increase does not exclude proliferative mastopathy with certainty. Patients with increased contrast uptake should be regarded as "high risk" and examined at regular intervals. PMID- 1617180 TI - [The place of mammography following breast-conserving therapy of breast cancer]. AB - This study evaluates the radiographical signs of the breast in 168 patients with breast carcinoma who were treated with lumpectomy and radiation therapy. Two thirds of the postsurgical scars were radiologically seen only up to two years after operation. One-third showed only discrete scarred tissue after this period. The most characteristic sign was the continuous diminution of the post-surgical and post-radiation lesions in the follow-up mammograms (scar densities, fibrosis and architectural distortions). Microcalcification highly suspicious of malignancy developed in 6%; one-third, however, proved to be benign. Acute and chronic edema were the most striking symptoms up to one year after radiotherapy; the final stage of the post-radiation alterations was breast fibrosis which demonstrated in 60% of the cases rather discretely. The recurrence rate was 7%. PMID- 1617181 TI - Statistical analysis of MRI parameters predicting malignancy in 141 soft tissue masses. AB - Since well-known grading parameters such as cellularity, mitotic rate, matrix and presence of necrosis all influence MRI signal intensity, the value of MRI in predicting malignancy is potentially high. To assess this value we studied retrospectively the findings in 141 soft tissue tumours (84 benign, 57 malignant) and evaluated a wide variety of MRI features (size, margins, signal homogeneity, shape, signal intensity, neurovascular and bone involvement, degree and pattern of enhancement and evidence of necrosis after injection of Gd-DTPA). Statistical analysis was carried out to determine accuracy of parameters individually and in combination, for predicting malignancy. Highest sensitivity was obtained for "absence of low signal intensity on T2" (100%), "mean diameter greater than 33 mm" (90%), and "inhomogeneous signal on T1" (88%). Highest specificity was obtained for "evidence of necrosis" (98%), "bone or neurovascular involvement or metastases" (94%), and "mean diameter greater than 66 mm" (87%). Association of best sensitivity and specificity was seen for "absence of low signal intensity on T2", "signal inhomogeneity on T1", and "mean diameter of the lesion greater than 33 mm" (81 and 81%). PMID- 1617182 TI - [Fibrin glue as intra-arterial embolization material in acute hemorrhage]. PMID- 1617183 TI - [Intercostal arterial embolization following thoracic trauma]. PMID- 1617184 TI - [Rhabdomyolysis in computed tomography]. PMID- 1617185 TI - [Simultaneous percutaneous internal drainage of a pancreatic pseudocyst and spontaneous catheter removal]. PMID- 1617186 TI - Effects of two viral inactivation methods on platelets: laser-UV radiation and merocyanine 540-mediated photoinactivation. AB - Two viral inactivation methods suggested for use with cellular blood products have been evaluated as to their effects on platelets. In the first study, it was proposed that pulsed laser-ultraviolet radiation (UVB) at 308 nm could favor photodamage to UVB-sensitive viral nucleic acid with minimal effects on blood platelets. A "window of efficacy" was observed with UVB doses of 10.5-21.5 J/cm2 at which 4-6 log10 poliovirus were inactivated while platelets were relatively tolerant. However, this "window" occurred only with low-intensity UVB radiation (less than or equal to 0.25 MW/cm2). Damage to platelet proteins, evident at high laser intensities, was probably due to multiple photon excitation of amino acids. In the second study, platelets and viruses were treated with the photosensitizer, merocyanine 540 (MC 540) (less than or equal to 24 micrograms/ml), and visible light (450-600 nm) (less than or equal to J/cm2). Activation of washed platelets by dye/light treatment resulted in a spontaneous release of serotonin, spontaneous aggregation, and marked morphological changes. Increasing concentrations of albumin in the suspension medium protected against dye-mediated photodamage to platelets, but also significantly reduced the antiviral activity of MC 540 and light. These results illustrate the relative sensitivities of platelets and viruses to two inactivation methods and the difficulty in optimizing inactivation of viruses and preservation of platelet function in a protein-rich medium. PMID- 1617187 TI - Merocyanine-sensitized photoinactivation of enveloped viruses. AB - A wide range of enveloped viruses, including human herpes simplex virus type 1, human cytomegalovirus, human T cell leukemia/lymphoma virus type I, human immunodeficiency virus type 1, Sindbis virus, and Friend erythroleukemia virus, are highly susceptible to merocyanine 540 (MC 540)-sensitized photoinactivation. By contrast, human pluripotent hematopoietic stem cells, red cells, factor VIII, and von Willebrand factor are much less sensitive. This suggests that MC 540 may be useful for the inactivation of enveloped viruses in blood and blood products. The dye has a low acute systemic toxicity, is rapidly eliminated from the blood stream, and has little or no mutagenic potential. The currently available data support the view that MC 540-sensitized photo-inactivation interferes with early events in the infectious process, notably the ability of the virus to adhere to and penetrate its host cell. The viral envelope is a major target of photodynamic damages which appear to be mediated at least in part by singlet molecular oxygen. PMID- 1617188 TI - Inactivation of viruses in red cell and platelet concentrates with aluminum phthalocyanine (AIPc) sulfonates. AB - Aluminum phthalocyanine tetrasulfonates (AIPcS) are photoactive compounds with absorption maxima at 665-675 nm. The inactivation of viruses (vesicular stomatitis virus, VSV; human immunodeficiency virus, HIV) added to either whole blood or red blood cell concentrates (RBCC) and platelet concentrates (PC) on treatment with tetrasulfonated AIPc (AIPcS4) was evaluated. Treatment of RBCC with 10 microM AIPcS4 and 44 J/cm2 visible light resulted in the inactivation of greater than or equal to 10(5.5) infectious doses (TCID50) of cell-free VSV, greater than or equal to 10(5.6) TCID50 of cell-associated VSV, and greater than or equal to 10(4.7) TCID50 of cell-free sindbis virus. Both greater than or equal to 10(4.2) TCID50 of cell-free and greater than or equal to 10(3.6) TCID50 of cell-associated forms of HIV were also shown to be inactivated. Encephalomyocarditis virus, used as a model for nonenveloped viruses, was not inactivated. Equivalent virus kill with Photofrin II required a substantially higher concentration of dye and longer exposure to visible light. Following AIPcS4 treatment, red cell integrity was well maintained as judged by the low level (less than 2%) of hemoglobin release immediately following treatment and on subsequent storage, by measurements of erythrocyte osmotic fragility, and by the normal recovery and circulatory survival on infusion of treated, autologous red blood cells in baboons. Treatment of PC with 10 microM AIPcS4 and 44 J/cm2 visible light also resulted in effective virus kill (greater than or equal to 10(5.5) TCID50) of VSV; however, both the rate and extent of platelet aggregation in response to collagen addition declined by at least 50%. Based on these results, further characterization of AIPcS4-treated RBCC is justified. PMID- 1617189 TI - Photoinactivation of lymphohemopoietic cells: studies in transfusion medicine and bone marrow transplantation. AB - Ultraviolet (UV) irradiation affects eukaryotic cells in numerous ways. Exposure of blood transfusion products to UVC (200-280 nm) or UVB (280-320 nm) reduces or abrogates their immunogenicity and thereby prevents allosensitization and transfusion refractoriness in several models. Although the exact mechanism is not known, in vitro studies suggest that UV exposure results in a loss of class II histocompatibility antigens from the cell surface, alterations of calcium homeostasis, and a lack of interaction between antigen presenting and responding cells. In the UVB and UVA (320-400 nm) range, lymphocytes appear to be more sensitive than hemopoietic cells. In murine transplant models, UVB irradiation of spleen and marrow cells can be used to prevent the development of graft-versus host disease while allowing for complete hemopoietic reconstitution. Furthermore, in clinical marrow transplantation, pilot studies of UVA in conjunction with psoralen administration have yielded encouraging results in patients with steroid refractory graft-versus-host disease of the skin. Thus, UV irradiation provides an interesting tool to study cell/cell and donor/host interactions and may have some applications in transfusion medicine and bone marrow transplantation. PMID- 1617190 TI - Photochemical inactivation of viruses and bacteriophage in plasma and plasma fractions. AB - Transfusion-associated transmission of viral diseases remains a problem. A number of methods have been developed to inactivate viral pathogens in plasma and plasma fractions, including: dry heating, wet heating, solvent-detergent treatment, and immunoaffinity purification. While some of these methods successfully inactivate pathogenic viruses, inactivation may be incomplete or result in damage to labile plasma proteins. We have developed a method of photochemical decontamination (PCD) using psoralens and long wavelength ultraviolet light to inactivate pathogenic viruses. In the present study, a spectrum of model viruses have been added to plasma and plasma fractions to examine the efficiency of photochemical decontamination and the effects on labile plasma coagulation factors. Both RNA and DNA viruses have been inactivated under conditions which permit preservation of coagulation protein function. PCD technology appears to offer a promising solution to decontamination of blood products. PMID- 1617191 TI - Photoinactivation of viruses and cells for medical applications. PMID- 1617192 TI - Factors influencing virus inactivation and retention of platelet properties following treatment with aminomethyltrimethylpsoralen and ultraviolet A light. AB - A wide variety of viruses are inactivated by psoralen compounds in the presence of ultraviolet A light (UVA). Use of aminomethyltrimethylpsoralen (AMT) and UVA is being evaluated as a method to inactivate viruses that may be present in platelet suspensions prepared for transfusion. Studies have been conducted to assess how variation in various environmental parameters influences the extent of viral inactivation and the retention of platelet properties. Most notably, it was determined that increasing levels of plasma progressively inhibited the inactivation of model viruses. As a result, experiments were routinely conducted at a plasma level of approximately 14.5%, using 40 micrograms/ml AMT, which was determined to be optimal when using this reduced plasma level. The reduced plasma level was achieved by dilution with a nonplasma medium that has been shown to be satisfactory for storage of platelets. Under these conditions, about 5 logs of vesicular stomatitis virus (VSV), pseudorabies, and phi 6 inactivation were achieved. Variation of platelet and leukocyte counts, within normal levels, had a minimal effect on extent of viral inactivation. Although oxygen level (mean levels, 97.9 mm Hg versus 19.2 mm Hg) had only a small influence on viral inactivation with 2.4, 4.8, and 7.2 J/cm2 of UVA (equivalent to 1-3 minutes of exposure), in vitro platelet properties, such as medium pH, morphology characteristics, and aggregation response, were better retained with a longer exposure time at the reduced oxygen level. With normal oxygen (97.9 mm Hg), platelet properties declined substantially relative to untreated controls (no UVA, no AMT) on exposure to 4.8 J/cm2. Our studies have identified two sets of conditions that provide about 5 logs of virus inactivation without extensively altering platelet in vitro properties. PMID- 1617193 TI - Use of 8-methoxypsoralen and long wavelength ultraviolet radiation for decontamination of platelet concentrates. AB - Transmission of viral diseases through blood products remains a problem in transfusion medicine. We have developed a photochemical decontamination system (PCD) for platelet concentrates (PC) utilizing treatment with long wavelength ultraviolet radiation (UVA, 320-400 nm) and 8-methoxypsorlan (8-MOP). This system is capable of inactivating 25-30 logs/hour of bacteria E. coli or S. aureus, 6 logs/hour of bacteriophage fd, 0.9 log/hour of bacteriophage R17, and 1.1 logs/hour of feline leukemia virus (FeLV) in PC. Immediately following 6 hours of PCD treatment, platelet integrity and function of PCD-treated and control PC were equivalent. After overnight storage, PCD-treated and control PC platelet properties were equal, but there was a slight reduction in TXB-2 production of PCD-treated PC compared to controls. Following PCD treatment, PC were stored for 48 to 96 hours. Platelet counts, morphology scores, extracellular LDH levels, aggregation response, dense body (db) content, and alpha granule (alpha g) content of PCD-treated and control PC were comparable. We assessed the ability of the PCD technique to inactivate intracellular and extracellular virus, quantified the degree of DNA adduct formation in contaminating lymphocytes, and measured the inhibition of polymerase chain reaction (PCR) mediated amplification of intracellular DNA. High titers of cell-free murine cytomegalovirus added to human platelet concentrates (final concentration 10(6)) were inactivated by PCD within 30 minutes. Cat renal fibroblasts infected at high levels with feline rhinotracheitis virus (FeRTV) were seeded into PC followed by PCD treatment with inactivation of 4.8 logs of FeRTV within 10 minutes. Purified human lymphocytes were seeded into PC and treated with PCD in the presence of 3H 8-MOP. Six hours of PCD treatment resulted in the formation of 9.3 to 12.8 8-MOP adducts per 1000 base pairs (bp) of DNA. PCR amplification of a 242 bp segment at the HLA-DQ alpha locus was examined. Inhibition of PCR DNA amplification was dependent on the numbers of 8-MOP adducts formed, and no amplification was present when greater than 12 adducts per 1000 bp were formed. These studies indicate that PCD can effectively inactivate high titers of cell-associated and cell-free virus seeded into standard human PC. The efficiency of DNA adduct formation can be quantitated, and the level of 8-MOP adduct formation in lymphocytes contaminating PC is comparable to the level of adduct formation in cellular DNA reported in the absence of platelets. PMID- 1617194 TI - Photochemical inactivation of viruses with psoralens: an overview. AB - In the presence of longwave ultraviolet light, psoralen derivatives photoreact with the nucleic acids within intact viruses and cells. This photoreaction can leave protein antigens and other surface components relatively unmodified, while eliminating the infectivity of a wide range of infectious agents. The kinetics of inactivation differ among RNA and DNA viruses photoreacted with different derivatives of psoralen. The inactivation kinetics are nonlinear as a result of photodegradation of psoralens and the unexplained biphasic inactivation of some viruses. In spite of these complexities, the photoreaction is capable of generating broad safety margins in the disinfection of microbial products under gentle, physiologic conditions. The psoralen photoreaction provides a potential method for inactivating both known and unknown viruses in active blood products. Psoralen-inactivated viruses have already proven useful as noninfectious antigens for use in immunoassays and as successful experimental vaccines. PMID- 1617195 TI - Inactivation of viruses with photoactive compounds. AB - The transmission of human immunodeficiency virus (HIV-1) and other enveloped virus by blood transfusion is a major concern. Photosensitive dyes such as hematoporphyrin derivative (HPD), dihematoporphyrin ether (DHE), benzoporphyrin derivatives (BPD), extended ring porphyrins, sapphyrins and texaphyrins, and various cyanines were used with viral cultures to test the feasibility of using those light-excitable dyes to kill virus. A photodynamic flow cell was used to irradiate viral suspensions or viral infected cells in culture media or in whole blood. Herpes virus (HSV-1) was used to screen compounds. Effective compounds were subsequently tested for their ability to kill HIV-1, CMV, and SIV in culture medium and in blood and proved to effectively kill free virus and infected cells at significant viremias. Irradiation was achieved with a filtered xenon light source and/or tunable dye laser. Concentrations of dyes at 10 times viral kill dose were irradiated in blood which was tested for damage to erythrocytes (RBC), platelets, and blood proteins. No damage to RBC, complement factors, and immunoglobulins was evident immediately after photodynamic treatment. Platelet condition is minimally modified with time. Photodynamic treatment of blood appears to be a feasible means of eradicating virus and some protozoans from blood. PMID- 1617196 TI - Risks of cancer associated with long-term exposure to PUVA in humans: current status--1991. AB - Since 1975 oral 8-methoxypsoralen administered in association with ultraviolet-A radiation (UVA), (PUVA) has been widely used to treat psoriasis and other cutaneous diseases. PUVA is mutagenic, and in animals carcinogenic. Prospective study of a cohort of patients with psoriasis who were first treated with PUVA in 1975-1976 has provided data on the carcinogenic risk of this treatment. There is a dose-dependent increase in the risk of squamous cell cancer of the skin associated with exposure to PUVA. A recent large-scale Swedish study confirmed this association. The risk of squamous cell cancer of the genitals of males exposed to high doses of PUVA is especially high. A consistent, confirmed, and significant relationship of exposure to PUVA to other types of malignancies in man has not been established. Although highly effective in the treatment of psoriasis, the risk of squamous cell cancer associated with long-term therapy with PUVA must be considered in determining when this therapy is appropriate for an individual patient. Additional study of PUVA-treated patients will better define the full spectrum of the carcinogenic risk of PUVA therapy and the clinical behavior of tumors that arise in association with this treatment. PMID- 1617197 TI - Pathogen-derived resistance to a potyvirus: immune and resistant phenotypes in transgenic tobacco expressing altered forms of a potyvirus coat protein nucleotide sequence. AB - Transgenic Nicotiana tabacum 'Burley 49' plants containing one of six different forms of the tobacco etch virus (TEV) coat protein (CP) nucleotide sequence have been generated. In whole plant studies, R1 and R2 progeny were inoculated mechanically with TEV, and the appearance and severity of symptoms were recorded. Symptom phenotype was altered, ranging from near wild type susceptibility to apparent immunity. Protoplasts derived from wild type and transgenic Burley 49 plant lines were transfected with TEV RNA. Protoplasts from transgenic plants expressing full-length or truncated forms of TEV CP supported virus replication. Protoplasts from certain transgenic plants, producing plus- or minus-sense CP transcripts but no CP, did not support virus replication at wild type levels. A model is proposed to account for these observations. PMID- 1617198 TI - Genetic analysis of the aggA locus involved in agglutination and adherence of Pseudomonas putida, a beneficial fluorescent pseudomonad. AB - An isolate of Pseudomonas putida, which rapidly adheres to plant roots, is agglutinated by a glycoprotein from root surfaces. Agglutination is prevented and adherence to the root surface is diminished by Tn5 insertion in mutant 5123. Two cosmid clones from wild type P. putida and a 2.7-kbp EcoRI-HindIII subclone present in both cosmid clones restored agglutinable to wild type levels in transconjugants of the nonagglutinable (Agg-) Tn5 mutant 5123. These three clones increased agglutinability in transconjugants of the parental Agg+ isolate. The 2.7-kbp EcoRI-HindIII subclone restored adherence to bean root surfaces of 5123 to wild type levels in a short-term binding assay. Deletion analysis of the 2.7 kbp fragment indicated only 1.45 kbp was necessary for complementation of agglutinability in 5123. This sequence, termed the aggA locus, contains an open reading frame of 1,356 nucleotides encoding a predicted 50,509-Da protein. The distribution of the aggA locus in plant-associated bacteria, as detected through Southern hybridization, is limited to bacteria that express the agglutination phenotype. PMID- 1617199 TI - Two C4-dicarboxylate transport systems in Rhizobium sp. NGR234: rhizobial dicarboxylate transport is essential for nitrogen fixation in tropical legume symbioses. AB - To investigate the role of dicarboxylate transport in nitrogen-fixing symbioses between Rhizobium and tropical legumes, we made a molecular genetic analysis of the bacterial transport system in Rhizobium sp. NGR234. This braod host range strain fixes nitrogen in association with evolutionarily divergent legumes. Two dicarboxylate transport systems were cloned from Rhizobium NGR234. One locus was chromosomally located, whereas the other was carried on the symbiotic plasmid (pSym) and contained a dctA carrier protein gene, which was analyzed in detail. Although the DNA and derived amino acid sequences of the structural gene were substantially homologous to that of R. meliloti, its promoter sequences was quite distinct, and the upstream sequence also exhibited no homology to dctB, which is found at this position in R. meliloti. A site-directed internal deletion mutant in dctA of NGR234 exhibited a (unique) exclusively symbiotic phenotype that could grow on dicarboxylates ex planta, but could not fix nitrogen in planta. This phenotype was found for tested host plants of NGR234 with either determinate- or indeterminate-type nodules, confirming for the first time that symbiosis-specific uptake of dicarboxylates is a prerequisite for nitrogen fixation in tropical legume symbioses. PMID- 1617200 TI - Transcriptional organization and expression of the large hrp gene cluster of Pseudomonas solanacearum. AB - Cloning and localized mutagenesis of the larger cluster of hrp genes of Pseudomonas solanacearum strain GMI1000 allowed the definition of the borders of this cluster, which now extends about 2 kb to the left of the insert of the previously described plasmid pVir2 (Boucher et al. 1987, J. Bacteriol. 169:5626 5632). The size of the cluster has also been expanded 3 kb to the right to include a region previously described as dsp; our present data demonstrate that insertions occurring in these 3 kb lead to leaky mutations affecting both pathogenicity on tomato and ability to induce the hypersensitive response (HR) on tobacco. Therefore, the size of the entire hrp gene cluster is estimated to be about 22 kb. The use of transposon Tn5-B20, which promotes transcriptional gene fusions, allowed us to demonstrate that the hrp gene cluster is organized in a minimum of six transcriptional units, which are transcribed when the culture is grown in minimal medium but are repressed during growth in rich medium or in the presence of peptone or Casamino Acids. The level of expression in minimal medium is modulated by the carbon source provided; pyruvate is the best inducer. Under these conditions the level of expression observed in vitro appears to be representative of the actual expression observed in planta. PMID- 1617201 TI - Bovine spongiform encephalopathy. AB - A detailed account is given of the occurrence of bovine spongiform encephalopathy (BSE), current research into the aetiology of this new disease of cattle, and the relationship between BSE, scrapie and other similar diseases. Epidemiology, clinical signs, pathology, diagnosis, prevention and control are described. PMID- 1617202 TI - Scrapie. AB - A detailed review is presented of the history, geographical distribution, cause, epidemiology, clinical features, pathogenesis, pathology, diagnosis, prevention, control and economic effects of scrapie in sheep. Brief mention is made of the disease in goats and moufflon. The nature of the agent causing scrapie, the genetic control of the incubation period in sheep and the natural transmission of scrapie in sheep and goats are discussed. National efforts to control scrapie in various countries are outlined. PMID- 1617203 TI - Spongiform encephalopathies in Cervidae. AB - The known host range of naturally-occurring transmissible spongiform encephalopathies has expanded in recent years to include wild ruminants. Chronic wasting disease (CWD) occurs in mule deer (Odocoileus hemionus hemionus) and Rocky Mountain elk (Cervus elaphus nelsoni) in Colorado and Wyoming, United States of America. These species belong to the family Cervidae. Cases have occurred primarily in captive animals but a few affected free-ranging animals have been identified. Clinical disease in both species is characterised by progressive weight loss, behavioural alterations and excessive salivation. In deer polydipsia and polyuria also commonly occur. Significant lesions are confined to the central nervous system and consist of spongiform change in grey matter, intraneuronal vacuolation, astrocytosis and amyloid plaques. Inflammatory reaction is absent. The origin of this disease is not known. In contrast to the cases of spongiform encephalopathy recognised in five species of antelope (family Bovidae) in British zoological parks, which are an extension of the current bovine spongiform encephalopathy epizootic, CWD is not the result of food-borne exposure to the infectious agent. CWD appears to be maintained within captive populations by lateral and, possibly, maternal transmission. Spongiform encephalopathies in wild ruminants are currently geographically isolated and involve relatively small numbers of animals. However, these potentially transmissible diseases could be of greater importance in the future and should be viewed with concern in the light of international movements of wild ruminants and the current expansion of the game farming and ranching industry in many parts of the world. PMID- 1617204 TI - Sub-acute, transmissible spongiform encephalopathies: current concepts and future needs. AB - The first diagnosis of bovine spongiform encephalopathy (BSE) in the United Kingdom in 1986 was to stimulate the most intensive epidemiological study of any animal disease of all time in that country. It led also to the initiation of a broad-based research programme with an international flavour. This principally involved scientists and veterinarians in Europe (especially the United Kingdom) and the United States of America, especially those with experience of slow infections in general and experimental scrapie in particular. This final chapter highlights some of the significant discoveries made in the study of BSE and related diseases of this group but also emphasises the deficits in knowledge which need to be corrected before such diseases as scrapie in sheep and goats can be brought under control. The benefits resultant upon effective disease control will be manifest as improvement in animal production, welfare and, importantly, the removal of trading barriers currently in place to protect countries in which diseases such as BSE and scrapie do not exist. Of key importance is the development of a simple, cheap and effective diagnostic test for use in the live animal before the onset of clinical signs. This will be difficult since the nature of the causal agents is uncertain and none provokes either a detectable immune response or inflammatory reaction in the host. The earlier chapters, written by acknowledged specialists from around the world, deal with the specific diseases in detail and all present some of the most recent knowledge available. Here the authors emphasise the important role that major national and international agencies have in effecting the highest level of control possible in the absence of key information. International collaboration with countries in which these diseases exist, and as well as those where they are absent, is of paramount importance. It is essential that the BSE epidemic which has severely affected the cattle industry of the United Kingdom is not allowed to happen in developing countries. Whereas the former has implemented stringent control measures based on scientific knowledge and is well on the way to eradicating the disease, the latter could have much greater difficulty in establishing control. The answer is clear. BSE must be prevented from occurring elsewhere. To do that, knowledge of BSE and other members of the group should be widely dispersed and it is the purpose of this issue to do just that. PMID- 1617205 TI - Role of ultrastructural studies in the analysis of cell lineage in the mammalian pre-implantation embryo. AB - Ultrastructural studies have contributed significantly to our understanding of cell lineage differentiation in the mammalian pre-implantation embryo. Such studies have documented, and continue to document, morphological, biochemical, and physiological characteristics of the cell lineages established during the pre implantation period in eutherian embryos, principally that of the mouse. This review evaluates these contributions and identifies areas of study in which ultrastructural analysis is most likely to have an important role in the future. PMID- 1617206 TI - Preservation and visualization of the sea urchin embryo blastocoelic extracellular matrix. AB - Several methods were utilized to visualize the structure and orientation of the blastocoelic extracellular matrix (ECM) in Strongylocentrotus purpuratus embryos at the mesenchyme blastula stage. Rapid freezing in liquid propane cooled to LN2 temperatures followed by freeze substitution was used to preserve the ECM without shrinkage due to dehydration. Scanning, transmission, and light microscopy were employed to elucidate the ECMs' structure. The blastocoelic ECM consisted of parallel fibrillar sheets that were interconnected by finer filaments and oriented along the animal-vegetal axis. The ECM completely filled the blastocoelic cavity as viewed by scanning electron microscopy. The basal lamina could be distinguished from the blastocoelic ECM as a thin coat on the plasma membrane of epithelial cells; the ECM was in contact with this coat. In contrast, the blastocoelic ECM attached directly to the plasma membrane of primary mesenchyme cells (PMC) which did not possess a basal lamina. The blastocoelic ECM was isolated as an intact "bag" and probed in a hydrated state with Con A and alcian blue. Confocal microscopy confirmed that the entire blastocoel was filled with a fibrillar ECM. These approaches offer advantages for future studies of the ECMs of sea urchin embryos and their roles in gastrulation. PMID- 1617207 TI - Role of the cytoskeleton during early development. AB - Oocytes, eggs, and embryos from a diverse array of species have evolved cytoskeletal specializations which allow them to meet the needs of early embryogenesis. While each species studied possesses one or more specializations which are unique, several cytoskeletal features are widely conserved across different animal phyla. These features include highly-developed cortical cytoskeletal domains associated with developmental information, microtubule mediated pronuclear transport, and rapid intracellular signal-regulated control of cytoskeletal organization. PMID- 1617208 TI - From egg to pole cells: ultrastructural aspects of early cleavage and germ cell determination in insects. AB - Insect eggs are giant and very complex cells covered by an extremely resistant shell. Both the egg cell and surrounding eggshell express anteroposterior and ventrodorsal polarity. The molecular and cytoplasmic organization of both axes originates during oogenesis and leads to the production of an ooplasmic system which consists of euplasm and deutoplasm (yolk) and contains a nucleus as well as extranuclear determinants of maternal origin. Both are part of the store of information for early embryogenesis. In addition, the deutoplasm serves as raw material and early nutrient supply for building the embryo. The insect egg cell, which is arrested in the first maturation division when released from the ovary during oviposition, will be activated by different stimuli among different species to complete meiosis and start embryogenesis. The zygote nucleus undergoes a number of synchronous mitotic divisions leading to cleavage energids which initially form a syncytial blastoderm and subsequently the cellular blastoderm. In many insects, prior to blastoderm formation, polar granules (or oosome material) are incorporated in a single cell or a small number of cells which bud off at the posterior pole. These so called pole cells give rise to the primordial germ cells. Therefore, polar granules or the oosome material mark the germ line, and while structural counterparts of determinants of body pattern formation have so far not been found, the polar granules or oosome serve as an autonomous ooplasmic determinant for the pole or germ cells. Anteroposterior body polarity can arise independent of the germ plasm. PMID- 1617209 TI - Cell lineage in molluscan development. AB - Cell lineage specification in molluscs is brought about by two mechanism: the segregation of morphogenetic plasms and inductive cell interactions. The evidence for the existence of morphogenetic plasms is largely circumstantial, but in one species, Bithynia, such a plasm has been identified in the polar lobe that forms at first cleavage. Inductive cell interactions are thought to be a prerequisite for the development of a large number of tissues and organs. The most extensively studied example is the specification of the mesodermal stem cell in Lymnaea and Patella, which occurs between 5th and 6th cleavage through an interaction between one macromere and a large number of micromeres. Both segregation and induction are tuned to the animal-vegetal polarity of the egg, at least during early development. This polarity probably arises during oogenesis and is manifest in regional differentiations of the surface architecture of the egg, in the distribution of inner membrane particles in the plasma membrane, in membrane fluidity characteristics, in ionic conductance properties of the plasma membrane, etc. All these phenomena have in common that they represent properties of the egg surface, suggesting that the polarity of the egg is somehow imprinted into the plasma membrane and the cortex of the egg during oogenesis. PMID- 1617210 TI - Secretion of macrophage cytotoxic factors induced by new desmuramyl acylpseudopeptide analogs of muramyl dipeptide. AB - Sixteen desmuramyl analogs of muramyl dipeptide (MDP) were tested for their abilities to stimulate cytotoxic factor secretion by mouse peritoneal macrophages. Among them, the pseudohexapeptide Boc-Gly psi [CH2O]-D-Ala-Ala-D Glu[Lys(H-Gly)NHEt]-NH2 appeared to be four times more effective than MDP. From this study, the D configuration of the pseudo-alanyl (or lactyl) residue appears to be essential for activity. PMID- 1617211 TI - Action of hydrazine drugs in tumor-free and 1,2-dimethylhydrazine-treated male rats. AB - In order to evaluate possible carcinogenesis, young adult male Sprague-Dawley rats were fed diets of hydralazine, phenelzine, and isoniazid at levels of 0.020 0.035% for 87 weeks. Hydralazine and isoniazid were also tested by the subcutaneous (sc) route at weekly dosages of 17 and 83 mg/kg, respectively, in both intact and partially hepatectomized rats, but many succumbed after 7 to 49 weeks of treatment. Gastrointestinal lesions were absent and, of the miscellaneous changes, sc lesions occurred sporadically among the control and drug-treated groups. As a further criterion, male weanlings were placed on the diets and, starting on day 15, 1,2-dimethylhydrazine (DMH) was injected sc at 9.0 mg/kg once weekly for the first 7 weeks and twice per week for a total of 23 treatments. The rats were killed 22 weeks after the last injection, at which time colon adenocarcinomas were observed in over 80% per group, the total number being significantly greater for the isoniazid group due to heightened tumor occurrence at the distal colon. The tumor number in the descending colon for phenelzine was also increased but the overall score, as with the hydralazine group, was in the range of the DMH injected controls. Small intestinal adenocarcinomas were lower in number and involved fewer rats on the hydralazine and phenelzine diets as compared to the isoniazid and control groups. Based on the current data, it is concluded that on long term exposure of DMH treated rats to the monoamine oxidase inhibitors, hydralazine and phenelzine are not cocarcinogenic, whereas isoniazid enhances colon carcinogenicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617212 TI - Reference listings in cancer research. PMID- 1617213 TI - Interstitial deletions in DiGeorge syndrome detected with microclones from 22q11. AB - DiGeorge syndrome in humans is characterized by immunodeficiency, heart defects, mental retardation and facial dysmorphism; cytogenetic analysis has shown that deletions at 22q11 occur in approximately 25% of cases. To generate DNA markers from this region, we have microdissected and microcloned band q11 of human Chromosome (Chr) 22. Nineteen thousand clones were obtained from material dissected from 20 chromosome fragments. Seventeen of 61 clones analyzed (28%) were repetitive, 27 (44%) gave no signal, and 17 (28%) detected single copy sequences of which ten mapped to Chr 22. Two of these were found to be deleted in patients with DiGeorge syndrome and either monosomy for 22q11-pter or visible interstitial deletions of 22q11. These two markers are also hemizygous in patients with no visible chromosomal abnormality, demonstrating that submicroscopic deletions are common in DiGeorge syndrome patients. PMID- 1617214 TI - Assignment of eight loci to bovine syntenic groups by use of PCR: extension of a comparative gene map. AB - The polymerase chain reaction (PCR) has been combined with hybrid somatic cell technology to extend the bovine physical map. Eight bovine loci--glycoprotein hormone alpha (CGA), coagulation factor X (F10), chromogranin A (CHGA), low density lipoprotein receptor (LDLR), human prochymosin pseudogene (CYM), oxytocin (OXT), arginine-vasopressin (ARVP), and cytochrome oxidase c subunit IV pseudogene (COXP)--were assigned to bovine syntenic groups with this approach. CGA was assigned to bovine syntenic group U2, F10 to U27, CHGA to U4 [bovine Chromosome (Chr) 21], LDLR to U22, CYM to U6, OXT and ARVP to U11, and COXP to U3 (bovine Chr 5). Seven of these genes, CGA, F10, CHGA, LDLR, OXT, ARVP, and CYM, further delineate regions of chromosomal conservation on human Chrs 6, 13, 14, 19, 20, 20, and 1, respectively. CHGA, OXT, and ARVP are unmapped in the mouse. Comparative mapping predicts the mouse CHGA will map to Chr 12, and mouse OXT and ARVP will map to mouse Chr 2. Furthermore, human CYM is predicted to be sublocalized to 1p32-q21. The primers developed for these eight loci will be useful for the development of hybrid somatic cell panels in the future as well as establishing a collection of bovine expressed sequence tags. PMID- 1617216 TI - Polymorphisms revealed by PCR with single, short-sized, arbitrary primers are reliable markers for mouse and rat gene mapping. AB - Ten single, arbitrarily designed oligodeoxynucleotide primers, with 50-70% (G+C) content, were used to amplify by polymerase chain reaction (PCR) sequences with DNA templates from several mouse species (Mus spretus, Mus musculus musculus, and Mus musculus domesticus), as well as DNA from the laboratory rat (Rattus norvegicus). Eight of these ten primers, used either individually or associated in pairs, generated a total of 13 polymorphic products which were used as genetic markers. All of these polymorphic sequences but one were mapped to a particular mouse chromosome, by use of DNA panels prepared either from interspecific backcross progeny of the type (C57BL/6 x Mus spretus)F1 x C57BL/6 or DNA samples prepared from two sets of recombinant inbred (RI) strains (AKXL and BXD). Six rat specific DNA segments were also assigned to a particular chromosome with DNA panels prepared from 18 rat/mouse somatic cell hybrids segregating rat chromosomes. From these experiments we conclude that, under precisely standardized PCR conditions, the DNA molecules amplified with these arbitrarily designed primers are useful and reliable markers for genetic mapping in both mouse and rat. PMID- 1617215 TI - Multilocus markers for mouse genome analysis: PCR amplification based on single primers of arbitrary nucleotide sequence. AB - Polymerase chain reaction (PCR) based on single primers of arbitrary nucleotide sequence provides a powerful marker system for genome analysis because each primer amplifies multiple products, and cloning, sequencing, and hybridization are not required. We have evaluated this typing system for the mouse by identifying optimal PCR conditions; characterizing effects of GC content, primer length, and multiplexed primers; demonstrating considerable variation among a panel of inbred strains; and establishing linkage for several products. Mg2+, primer, template, and annealing conditions were identified that optimized the number and resolution of amplified products. Primers with 40% GC content failed to amplify products readily, primers with 50% GC content resulted in reasonable amplification, and primers with 60% GC content gave the largest number of well resolved products. Longer primers did not necessarily amplify more products than shorter primers of the same proportional GC content. Multiplexed primers yielded more products than either primer alone and usually revealed novel variants. A strain survey showed that most strains could be readily distinguished with a modest number of primers. Finally, linkage for seven products was established on five chromosomes. These characteristics establish single primer PCR as a powerful method for mouse genome analysis. PMID- 1617217 TI - Random sequence oligonucleotide primers detect polymorphic DNA products which segregate in inbred strains of mice. AB - The random amplification of polymorphic DNA (RAPD) using primers of arbitrary nucleotide sequence has been extremely valuable in identifying heritable markers in a variety of systems. The present studies examined whether the RAPD technique can identify large numbers of polymorphisms that can be used to construct genetic maps in inbred strains of mice. By screening the inbred mouse strains C57BL/6J and DBA/2J with 481 random 10-mer oligonucleotide primers, we identified 95 polymorphisms and mapped 76 of these by use of the BXD series of recombinant inbred (RI) strains. The results clearly demonstrate that the RAPD technique allows for the identification of large numbers of DNA-based polymorphisms that distinguish these two inbred strains of mice, and that such markers can readily be used to construct molecular genetic linkage maps. PMID- 1617218 TI - Genomic mapping within the albino-deletion complex using individual early postimplantation mouse embryos. AB - Sensitive methods for analysis of DNA from limited amounts of tissue are often difficult, error prone, and time consuming. Here, we describe a procedure for molecular analysis of individual early postimplantation mouse embryos by Southern analysis. The procedure involves embedding single embryos in agarose before lysing and deproteinizing in situ. The embedded DNA can be digested with restriction enzymes and analyzed by standard Southern-blotting procedures. The procedure is sensitive enough to detect single-copy sequences in embryos as early as day 6.5 of development. We have used the technique to genotype embryos homozygous for an embryonic lethal deletion. Normally, the lethal phenotype associated with such mutations is identified by a retrospective statistical analysis of abnormal embryos produced from a heterozygous cross as compared to those produced from a control cross. Now, if associated with a detectable DNA abnormality, the mutant embryo can be genotyped directly. We also report the use of this method for mapping cloned markers relative to deletion breakpoints. This approach can save considerable time since mapping would conventionally be done using restriction fragment length polymorphisms (RFLPs) detected in Mus musculus/Mus spretus interspecies hybrids. Using this procedure, we have been able to redefine the distal limits of the region of Chromosome (Chr) 7 containing a gene (eed) needed for development of the embryonic ectoderm. PMID- 1617219 TI - Molecular analysis of human chromosome 16 cosmid clones containing NotI sites. AB - To test the feasibility of using cloned NotI sites as markers for physical mapping, we have screened for cosmid clones spanning the NotI sites on human Chromosome (Chr) 16. Fluorescence in situ hybridization analysis of these clones confirms the previously reported cluster of NotI sites on 16p13.3. Methylation status of the cloned NotI sites on genomic DNA was established by hybridization of the cosmids to Southern blots containing EcoRI and EcoRI/NotI digest of genomic DNA. These results indicated that four of six clones included in our study can be used as linking clones for physical mapping. Two clones have NotI sites which are not cleavable in the cell lines tested. In one clone, the NotI site exists as an isolated rare-cutting restriction enzyme site, whereas in the other clone the NotI site appears to be island-related. PMID- 1617220 TI - Long-range walking techniques in positional cloning strategies. PMID- 1617221 TI - Mapping and expression of the ubiquitin-activating enzyme E1 (Ube1) gene in the mouse. AB - The nucleotide sequence of the human cDNA encoding ubiquitin-activating enzyme E1 is more than 99% identical with the human A1S9T cDNA, a gene that has been shown to complement the temperature-sensitive mutant mouse cell line, tsA1S9. The amino acid sequences of the proteins encoded by these two cDNA sequences are identical, and both cDNAs were previously shown to be located in the same region of the human X chromosome; thus, ubiquitin-activating enzyme E1 and A1S9T appear to be the same gene, designated UBE1. By in situ hybridization to metaphase chromosomes from male mice and by Southern blot analysis of male and female mouse DNA, we show that, in the mouse, a human UBE1 cDNA probe identified both X- and Y-linked loci. Ube1 is located at band A2 of the mouse X Chromosome (Chr) and Ube2 on the short arm of the Y Chr. This is in contrast to the situation in the human, where there is no evidence for Y-linked sequences related to UBE1. Mapping of the Ube1 gene in interspecific backcrosses between Mus spretus and C57BL/6 shows that the Ube1 locus maps close to Timp, in a conserved region of the mouse and human X Chrs that include Otc, Cybb, Syn1, Timp, and Araf. Expression of Ube1 on the inactive X Chr was examined to determine whether this gene is subject to X-Chr inactivation in the mouse, as there is previous evidence that the human UBE1 gene escapes, at least partially, X inactivation. Sequencing of reverse transcriptase polymerase chain reaction (RT-PCR) products from M. spretus, C57BL/6J, and T(X;16)16H x M. spretus F1 female mice indicates that the mouse Ube1 gene is subject to X-Chr inactivation in vivo. This represents a new example of differences between the sex chromosomes of mouse and human. PMID- 1617222 TI - Organization and chromosomal locations of Rap1a/Krev sequences in the mouse. AB - The human RAP1A gene encodes a protein that apparently can antagonize the function of oncogenic ras genes in gene transfer experiments, but its normal function is unknown. To understand the function of this gene, we have undertaken a study of the mouse homolog, Rap1a. The complete coding sequence of a mouse Rap1a cDNA has been determined, and genomic clones representing three distinct Rap1a species were recovered. We find that Rap1a is located on distal mouse Chromosome (Chr) 3 near Nras, Ampd-1, Tshb, Ngfb, and Atp1a1. Two related sequences (Rap1a-rs1 and Rap1a-rs2) were also characterized. Rap1a-rs1, which was not localized, has a sequence very similar to the Rap1a cDNA, suggesting that it has been recently acquired by the mouse genome. Rap1a-rs2 is more distantly related to the gene sequence and is located on Chr 2 near Actc-1. PMID- 1617223 TI - Completion of the physical map of Xq28: the location of the gene for L1CAM on the human X chromosome. AB - The gene for the neural cell adhesion molecule L1 (L1CAM) has been shown to be located close to the color vision pigment genes in mouse and man. This location has been confirmed by a number of different mapping strategies in both species. With pulsed field gel electrophoresis it has been proposed that L1CAM lies between the RCP, GCP, and GDX, G6PD loci. We report here a reinterpretation of the location of this gene, based on the physical linkage of L1CAM to the more proximal locus DXS15. This places L1CAM between this marker and the color vision genes (RCP, GCP), a region very dense in CpG islands, expected to contain a large fraction of the disease genes assigned to the Xq28 region. In combination with the physical mapping data on Xq28 described previously, this closes the last remaining gap in the map of the Xq27-Xq28 region. This removes the last contradiction between the maps of this region in the genomes of man and mouse, and confirms the close similarity of order and distances of markers between these organisms. PMID- 1617224 TI - Methylation status of ribosomal RNA gene clusters in the flow-sorted human acrocentric chromosomes. AB - Southern blot analysis of the human acrocentric chromosomes that were flow-sorted from B-lymphoblastoid cell line GM130B revealed that the sensitivity of the ribosomal RNA (rDNA) gene clusters to the restriction enzyme NotI differs among these rDNA-containing chromosomes: the rDNA clusters of Chromosomes (Chr) 13, 14, and 15 are much more sensitive to NotI digestion than those of Chrs 21 and 22 in this particular cell line. Detailed analysis by use of methylation-sensitive enzymes HpaII and HhaI and methylation-insensitive enzyme MspI confirmed the significant variation in the methylation status of rDNA clusters among these chromosomes. Quantitative analysis by fluorescent in situ hybridization (FISH) indicated that copy number of rDNA varies among individual chromosomes, but the average copy number in the acrocentric Chrs 21 and 22 is significantly greater than that of the Chrs 13, 14, and 15 in GM130B cells. Similar analysis reveals that the methylation status of rDNA clusters in another B-lymphoblastoid cell line GM131 was different from that of GM130B. These data together indicate that the copy number and methylation patterns of rDNA clusters differ among individual acrocentric chromosomes in a given cell line, and they are different among cell lines. PMID- 1617225 TI - A human chromosome 7-specific genomic DNA library in yeast artificial chromosomes. PMID- 1617226 TI - Localization of murine HLH gene NSCL to chromosome 1 by use of recombinant inbred strains. PMID- 1617227 TI - TPA-induced differentiation of rat aortic endothelial cells is substrate-specific and receptor mediated. AB - Under normal conditions, the morphology of cultured endothelial cells (EC) is characterized by a contact-inhibited monolayer with a distinct cobblestone appearance. However, when treated with phorbol esters, EC acquire fibroblast-like growth characteristics, are no longer contact-inhibited in growth, become invasive and form pre-capillary, tubular structures within collagen matrices. These events describe the basic processes of angiogenesis. We characterized the early effects of phorbol-12-myristate-13-acetate (TPA) on the attachment and spreading of rat aortic endothelial cells (RAEC) to purified extracellular matrix proteins by analyzing the distribution of fibronectin integrin receptors and the organization of cytoskeleton microfilaments during RAEC spreading on four different extracellular matrix peptides (i.e., Collagen Types I and IV, fibronectin and laminin). Type IV collagen appeared to be the best substrate for RAEC adhesion and spreading while laminin proved to be the poorest. TPA (0.1 micron) decreased the rate of RAEC spreading on Type IV collagen with a subsequent delay in cell-cell contact formation. In contrast, TPA increases the rate of spreading and cell-cell contact formation of RAEC plated on laminin. PMID- 1617228 TI - Aortic endothelial cells in culture: factors which modulate their morphological and biosynthetic phenotypes. PMID- 1617229 TI - The behaviour of pericytes in vitro: relevance to angiogenesis and differentiation. PMID- 1617230 TI - Identification of non heparin-binding endothelial cell growth factor from rat myofibroblasts. AB - Myofibroblasts (Mfs) from rat fat tissues produced a potent endothelial cell growth factor (Mf-ECGF). The growth factor activity found in the conditioned media from primary cultures of Mfs, was labile to heat (80 degrees C for 10 min) and proteinase (trypsin), and did not bind to heparin in the presence of 0.2 M NaCl. Mf-ECGF was partially purified 4760-fold with a recovery of 25% from serum free conditioned media by sequential carboxymethyl (CM) ion-exchange column chromatography and gel filtration. This Mf-ECGF activity was recovered from the 40 kD region of a non-reducing SDS-PAGE, and from the pH region between 6.5 and 7 of isoelectric focusing, with recoveries of 20% and 65%, respectively. These results indicated that a major portion of ECGF activity in the conditioned media was clearly distinct from other well-known endothelial cell growth factors including fibroblast growth factors (FGFs). PMID- 1617231 TI - Possible mechanisms of type I collagen-induced vascular tube formation. AB - We investigated the effect of type I collagen on endothelial behaviour following its contact with the apical versus basal surface of cultured human endothelial cells. When endothelial cells were plated onto type I collagen they attached via their basal surface and formed a confluent monolayer. However, when type I collagen (100 micrograms/ml) was added directly to the growth medium, so that it made contact with the apical surface of endothelial cells, it induced rapid capillary-like tube formation. Possible mechanisms were assessed using a) polyclonal (anti-VLA-2) and monoclonal (AK7) antibodies to different epitopes on the alpha 2 beta 1 integrin receptor for collagen and b) drugs (chlorpromazine and trifluoperazine) that inhibit protein kinase C activity. Both anti-VLA-2 and AK7 (1-50 micrograms/ml) showed a dose-dependent inhibition of tube formation and cell attachment. At 50 micrograms/ml, anti-VLA-2 completely inhibited tube formation whereas AK7 caused only partial inhibition (less than 50%). By contrast, AK7 was a more potent inhibitor of cell attachment than anti-VLA-2. Both chlorpromazine and trifluoperazine prevented tube formation. CONCLUSIONS: 1) The alpha 2 beta 1 integrin receptor plays a role in both endothelial cell attachment and the induction of tube formation by type I collagen. 2) Protein kinase C may be involved in collagen-induced tube formation. PMID- 1617232 TI - Basic fibroblast growth factor bound to cell substrate promotes cell adhesion, proliferation, and protease production in cultured endothelial cells. PMID- 1617233 TI - Thrombospondin modulates basic fibroblast growth factor activities on endothelial cells. AB - We previously reported that thrombospondin (TSP) induces endothelial cell (EC) adhesion, spreading and motility, suggesting that it can play a role in angiogenesis. We then studied whether TSP might modulate EC response to known angiogenic stimuli in vitro. Here we describe that TSP inhibits EC chemotactic response to basic fibroblast growth factor (bFGF). Furthermore, TSP and its 140 kD fragment reduce EC proliferative response to serum and bFGF. These data support the indicated role of TSP and its 140 kD fragment in angiogenesis and in related pathologies including tumor malignancy. PMID- 1617234 TI - Liver or lung colonization by F9 teratocarcinoma cells follows specific interactions with the target organ. PMID- 1617235 TI - Intussusceptive microvascular growth, a new mechanism of capillary network formation. AB - Growth by intussusception is defined as growth by deposition of new particles or pieces of formative material among those already embodied in a tissue or structure. In the context of capillary growth the term stands for the extension of the capillary system by the insertion of new capillary meshes within the existing network. New meshes arise as slender transcapillary tissue pillars. These are formed initially by a circumscribed fusion of opposite endothelial leaflets. Following reorganization of the junctional complexes, the pillar is invaded by interstitial tissue. This means that for the formation of new capillaries no sprouting of endothelial cords or tubules is required. The mechanism is described in the growing lung, but may occur in other tissues too. There may be a chance for in vivo observation of the process in the capillaries of the chorio-allantoic membrane of the chicken. PMID- 1617236 TI - The effect of angiotensin II on tumor blood flow and the delivery of microparticulate cytotoxic drugs. AB - Colorectal hepatic metastases have a notoriously poor response to conventional systemic chemotherapy. We have synthesised cytotoxic drug (doxorubicin and mitomycin C) containing spheres 40 microns in diameter, using human albumin and ethyl cellulose as matrices. Introduction of these cytotoxic microspheres into the hepatic artery should embolise to the tumor and provide a controlled release depot for the anticancer agent. The vasoconstrictor, angiotensin II (AII) has been shown to increase tumor blood flow relative to normal tissue when administered via the hepatic artery, therefore we have investigated the effect of AII on targeting of cytotoxic microspheres to hepatic metastases. Patients with hepatic metastatic colorectal carcinoma had hepatic arterial catheters inserted at laparotomy and connected to subcutaneous injection ports. Peroperatively, 99mTc-labelled albumin microspheres were administered via the arterial catheter. Fifteen minutes later, AII was infused (10 micrograms per minuter for 4 min) via the catheter and 131I-labelled albumin microspheres were administered as a bolus at the midpoint of the AII infusion. Multiple biopsies were taken of normal liver and tumor metastasis and the tissue radioactivity counted for 99mTc and 131I. Further studies were performed postoperatively in which 99mTc-labelled microspheres were administered via the hepatic artery catheter and their distribution was followed using tomographic SPECT scanning. Combined results of this study suggested that AII can increase tumor SPECT scanning. Combined results of this study suggested that AII can increase tumor blood flow rates relative to normal hepatic tissue by approximately 3-fold. PMID- 1617237 TI - Effects of hypercholesterolemia on monokine-induced smooth muscle cell proliferation. AB - Macrophage/smooth muscle cell interactions play a role in atherogenesis and foreign body reactions to biomaterials. This study investigates the effect of a hypercholesterolemic diet on the ability of smooth muscle cells (SMCs) to respond to monokines which are produced in response to hypercholesterolemia, biomaterials or both. Peritoneal macrophages were harvested from rabbits fed either a normal (M phi NL) or a 2% cholesterol/6% peanut oil diet (M phi ATH) (plasma cholesterol 2840 vs 42.3 [p less than 0.005]). The macrophages were then cultured in the presence of either 1) polyglactin 910 (PG910), 2) Dacron, or 3) no biomaterial (control), and the media collected and pooled by week for the smooth muscle cell mitogenesis assays. Rabbit aortic smooth muscle cells were harvested and cultured from the same two groups of rabbits (SMCNL or SMCATH), quiesced in serum free media (48 h) followed by addition of the test media and 3H-TdR. The addition of either biomaterial to M phi NL-conditioned media increased 3H-TdR incorporation in both smooth muscle lines as compared to controls. PG910 resulted in significantly higher 3H-TdR incorporation than Dacron (weeks 3-5, p less than 0.005). The addition of either biomaterial to M phi ATH also increased 3H-TdR incorporation in both smooth muscle cell lines, however, the magnitude of the response was decreased as compared to the M phi NL-conditioned media in both cell lines (p less than 0.001 for either SMC line). In contrast to the M phi NL conditioned media, the addition of Dacron to M phi ATH resulted in the highest level of 3H-TdR incorporation in both cell lines as compared to the media without biomaterial. The SMCNL had a higher response to both the monokines in conditioned media (2-fold) and to fetal bovine serum (3-fold) than the SMCATH (p less than 0.001). Although there is a generalized decrease in release of mitogens active on SMCs from M phi ATH, the M phi ATH exposed to Dacron release increased amounts of mitogenic factors, most active on the SMCATH cell line. A common mode of failure of small diameter Dacron grafts in man is pseudointimal hyperplasia, and it is inviting to postulate that the Dacron/macrophage/smooth muscle cell interactions in this atherosclerotic group of patients plays a role in the pathogenesis of this lesion. PMID- 1617238 TI - A bone tissue integrated single fibre laser Doppler flowmeter probe. AB - Laser Doppler Flowmetry was developed and evaluated mainly for measuring blood flow in exposed or superficial tissue layers like skin. Results showed large variation coefficients between juxtaposed skin sites with apparently homogeneous blood perfusion. Spatial differences in blood flow as well as anatomical differences probably explain the obtained results. Vasomotion, hereto only discovered with a microscopic technique, was recorded and evaluated for the first time. Similar results had been obtained in previous bone perfusion studies. The LDF technique has also been used extensively for skin irritancy tests and microvascular effects of vasoactive substances and drugs. An in vivo model in calibrating LDF quantitatively showed a linear relationship between LDF output signal and total blood flow in the range 0-300 ml min-1 100 g-1. This quantitative calibration is however tissue specific. Most tissues of interest are not superficial. The single fibre LDF provides additional power in studying deep tissue physiology and trauma-induced changes in regulation of microvascular perfusion. Furthermore long-term studies require implantable and biocompatible probes and this could be fulfilled using the SFLDF technique in combination with a tissue-integrated titanium probe. Implantation of the titanium probes initially creates some trauma to the vascular bed in the bone marrow but almost none in the opposite cortical bone layer. The healing process enhances the blood perfusion during the first weeks. The increased perfusion can be due to different parameters such as angiogenesis. The histological findings support this hypothesis. This gives preference to the tissue-integrated probe where interference with the tissue should be avoided. The integrated probe technique has only been evaluated in bone tissue. Modification of the probe shape and dimension, however, would make it suitable for other tissues as well. PMID- 1617239 TI - Role of basic fibroblast growth factor in proliferation of endothelium and smooth muscle after denuding injury in vivo. PMID- 1617240 TI - The direct effect of light therapy on endothelial cell proliferation in vitro. AB - During repair, new blood vessels are formed by the process of angiogenesis. The prerequisite to blood vessel formation is the proliferation of endothelial cells. The purpose of this study was to find out if light therapy is capable of affecting endothelial cell proliferation in vitro. The direct effect of light at wavelengths of either 660 or 820 nm was studied on primary cultures of bovine aortic endothelial cells using varying energy densities, of either 1, 2, 4, or 8 J/cm2. The proliferation of the endothelial cells was assessed over a period of five days after a single irradiation. PMID- 1617241 TI - Reactions of microvascular endothelial cells to tumor necrosis factor in vivo. PMID- 1617242 TI - FDA regulations for growth factors and related products. AB - Biological products, including the majority of growth factors, are regulated by the Center for Biologics Evaluation and Research (CBER) in the U.S. Food and Drug Administration (U.S.FDA) under two statutes; U.S. Federal Food Drug and Cosmetics (FDC) act and the U.S. Public Health Service act. As stipulated in the U.S. Code of Federal Regulations (21 CFR) under the FDC act, the testing of new products in humans is conducted under an Investigational New Drug (IND) application. The primary objective of the FDA in all Phases of an investigation is assure safety of human subjects. During phase II and phase III studies, additional assurance regarding the scientific quality of the clinical investigation is required. A marketing approval is granted by CBER following the review of Product License Applications (PLA) and Establishment License Applications (ELA). CBER's review process provides guidance to the manufacturers of biological products towards the development of safe and effective biological products for human use. Information pertinent to preclinical issues and clinical trial design is presented here with a special emphasis on the non-hematopoietic growth factors. PMID- 1617243 TI - Correlation of cervicovaginal fluid volume with serum estradiol levels and total follicular volume during human gonadotropin stimulation. AB - During the normal menstrual cycle the volume of cervicovaginal fluid (CVF), as determined by the patient at home using a simple volumetric aspirating pipette, increases significantly over several days prior to the luteinizing hormone (LH) surge and decreases characteristically shortly after ovulation. The present study was undertaken to test the hypothesis that self-determined measurements of CVF volume would correlate positively with serum estradiol (E2) levels and with total follicular volume (TFV) in cycles stimulated with exogenous gonadotropins. Consequently, 20 infertility patients, undergoing human menopausal gonadotropin (hMG)-stimulated cycles, were asked to measure daily CVF. Routine serum E2 determinations and vaginal follicular ultrasound studies were performed up to and including the day of human chorionic gonadotropin (hCG) administration (designated day 0). The mean daily CVF volume (+/- SD) increased from 0.1 +/- 0.01 ml on day -6 to 0.7 +/- 0.40 ml on day -1 and then decreased to 0.6 +/- 0.40 ml on day 0. On day 0, 7 of 20 cycles (35%) demonstrated a decrease in CVF, which ranged from 0.1 to 1.0 ml (mean, 0.42 ml). The mean daily CVF correlated positively (correlation coefficient = r) with the mean daily serum E2 (r = 0.89) and with the mean daily TFV (r = 0.88). The mean daily correlation of TFV for E2 was r = 0.98. The correlation between CVF and E2 of individuals ranged from r = 0.38 to r = 0.99 and the correlation between CVF and TFV ranged from r = 0.12 to r = 1.0, while the individual correlations of E2 to TFV ranged from r = 0.60 to r = 0.99.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617244 TI - In vivo fertilization procedures in infertile women with patent fallopian tubes: a comparison of gamete intrafallopian transfer, combined intrauterine and intraperitoneal insemination, and controlled ovarian hyperstimulation alone. AB - This prospective study was undertaken to evaluate the relative efficacy of three in vivo methods of assisted fertilization in 150 infertile women with patent fallopian tubes: gamete intrafallopian transfer (GIFT), combined intrauterine and direct intraperitoneal insemination (IUI+DIPI), and controlled hyperstimulation (COHS) alone. The clinical pregnancy rate was highest in the IUI/DIPI and GIFT groups: IUI/DIPI, 29.3%; GIFT, 28.6%; and COHS, 8.9%. We believe that controlled ovarian hyperstimulation combined with IUI and DIPI is a good alternative to GIFT. PMID- 1617245 TI - Motives for parenthood and response to failed in vitro fertilization: implications for counseling. AB - The purpose of this investigation was to identify in vitro fertilization (IVF) candidates' motives for parenthood and hence for seeking treatment. The relationship among identified motives, pretreatment emotional adjustment, and reaction to treatment failure was then examined. Women as a group placed greatest emphasis on fulfilling gender-role requirements, and those strongly endorsing such motives showed the poorest adjustment before IVF and the most negative reaction to first-cycle failure. In contrast, men in general were more likely to stress a desire for marital completion, although this motive was not predictive of emotional status before or after IVF. However, men experiencing social pressures to have children were at greater risk when treatment failed. The results indicate that greater consideration of cognitive factors may enhance understanding of emotional reactions to IVF failure and provide important insights for therapeutic intervention. PMID- 1617246 TI - Religious views regarding treatment of infertility by assisted reproductive technologies. PMID- 1617247 TI - Fertilizing capacity of various populations of spermatozoa within an ejaculate. AB - To determine whether ejaculates consist of various populations of sperm with varying degrees of fertilizing capacity, semen was filtered through a glass-wool column and the filtrate aliquoted sequentially into three portions. The ejaculate and its respective filtrates were evaluated for progressive motility, ability to respond to hypoosmotic swelling (HOS) test, acrosin content, ability to capacitate and acrosome react (AR), and ability to penetrate into denuded hamster oocytes (SPA). Filtrate 1 contained significantly more sperm with progressive motility, increased acrosin content, and positive HOS and SPA results than did the ejaculate. AR did not differ between the ejaculates and the respective filtrates. The data suggest that the ejaculate consists of various populations of sperm with different properties and that these populations may be separated by glass-wool filtration. PMID- 1617248 TI - Microscopic epididymal sperm aspiration (MESA): a new option for treatment of the obstructive azoospermia associated with cystic fibrosis. AB - Cystic fibrosis is a life-threatening disease. Only recently has the prognosis improved. In the male patient there is an almost invariable absence or maldevelopment of the vas deferens, creating a situation of obstructive azoospermia. Consequently, their fertility potential has been considered nonexistent. Having gained experience in microscopic epididymal sperm aspiration coupled with the advanced reproductive technologies for the treatment of congenital absence of the vasa, we sought to extend this treatment option to the male cystic fibrosis population. An Indian male with clinically evident and genetically confirmed cystic fibrosis underwent microscopic retrieval of epididymal sperm. The anatomy of the epididymis and the quality of sperm obtained were similar to those patients with congenital absence of the vas deferens. After appropriate spousal genetic testing, superovulation, and transvaginal oocyte retrieval, in vitro insemination of sperm was performed. Fifty percent of the oocytes were subjected to partial zona dissection and a single embryo resulted. Subsequent to transfer, no conception was realized but the effort expanded the clinical usefulness of microscopic epididymal sperm aspiration. This should open up an avenue of treatment for couples in whom only the most dire predictions for fertility have been made to date. PMID- 1617249 TI - Culture of human spare preembryos: association between blastocyst formation and pregnancy. AB - The rate of blastocyst development was studied in cultures of human fertilized eggs. A total of 195 spare embryos from 86 cycles in 73 in vitro fertilization (IVF) patients resulted in a total of 77 expanded blastocysts, corresponding to an overall blastocyst development of 39%. In the group of patients where pregnancy occurred, at least one of the spare embryos developed into the blastocyst stage in 100% of the patients, while the corresponding figure for nonpregnant patients was 53%. Superficially these results seem to indicate that blastocyst development could be of decisive importance for the success rate in IVF. A detailed analysis revealed, however, that this is not the case as long as in vitro culture before replacement is limited to 2-3 days. PMID- 1617250 TI - Effects of human sera and human serum albumin on mouse embryo culture. AB - Human proteins normally used to supplement human in vitro fertilization-embryo transfer (IVF-ET) culture media were tested for their effects on mouse embryo development from the zygote stage. These proteins included follicular and luteal phase maternal sera, fetal cord sera, and both human and bovine serum albumin. Our results revealed that both maternal and fetal cord sera did not permit mouse blastocyst formation. Furthermore, predialysis of the human maternal sera and removal of IgG by protein A column chromatography did not improve their support of mouse embryonic development to the blastocyst stage. Similar detrimental effects were observed with maternal sera from term-pregnant IVF-ET patients. Interestingly, these serum samples had supported the in vitro growth of the human zygotes which resulted in these patients' pregnancies. Only some batches of human serum albumin supported mouse blastocyst formation, whereas all sources of bovine serum albumin were effective in this regard. These results raise the question of the suitability of the mouse embryo culture system as a quality control for the testing of protein supplements for human IVF-ET. PMID- 1617251 TI - Successful use of the sperm motility enhancer 2-deoxyadenosine in previously failed human in vitro fertilization. AB - The outcome of in vitro fertilization treatment in male-factor infertility is generally poor, due mainly to poor fertilization rate and hence fewer available embryos for replacement. This study was carried out to assess the value of asthenospermic sperm exposure to a motility enhancing agent, 2-deoxyadenosine (2 DXA), on our in vitro fertilization program in couples undergoing repeat treatment after previous failed fertilization. Following sperm wash and incubation in 2-DXA-supplemented medium, marked significant improvements were observed in the sperm motility pattern and the number of recoverable sperms as compared to control unexposed samples. There was also a significantly better fertilization rate and higher number of replaceable embryos available following sperm wash in 2-DXA as compared to those washed without it. Following embryo transfer, pregnancy rate was comparable to the generally reported pregnancy rates for routine in vitro fertilization and embryo transfer treatment. Three normal babies were born. Our results indicate that 2-DXA enhances fertilization rate in some asthenospermic patients and that it has no adverse effect on embryonic development. PMID- 1617252 TI - Chromosomal analysis of pregnancy losses in patients undergoing assisted reproduction. AB - Chromosomal analysis was performed on products of conception from 18 patients having early pregnancy loss after assisted reproduction. Sonographic findings prior to obtaining tissue varied from gestational sacs consistent with a blighted ovum to fetal poles with cardiac activity. The mean age of the patients was 36.3 years. There were nine (50%) normal karyotypes, five (28%) autosomal trisomies, two cases of tetraploidy, one case of monosomy, and a case with two pericentric inversions. The results of this study suggest that patients undergoing assisted reproduction are not at an increased risk for chromosomal abnormalities. PMID- 1617253 TI - Factors associated with premature chromosome condensation (PCC) following in vitro fertilization. AB - From January 1989 to July 1990 a total of 562 oocytes was fixed in our In Vitro Fertilization Program, while cytogenetic data were collected in the case of 433. Forty-eight of these (11%) had a set of oocyte chromosomes in metaphase II, and at least one other set of sperm chromosomes prematurely condensed in the form of single chromatids. In the literature this phenomenon, frequent in our experience, has not been separately studied by many authors. Comparative studies with diverse parameters have shown a significant correlation between the same phenomenon and the use of follicle-stimulating hormone supplementation in ovarian stimulation protocols. Also, in some cases we found a high percentage of repetition of the phenomenon in one patient. PMID- 1617254 TI - Triploidy after in vitro fertilization: cytogenetic analysis of human zygotes and embryos. AB - Tripronuclear zygotes obtained from a clinical IVF program were studied cytogenetically. Successful analysis was possible of 42 specimens at the zygote stage and 21 embryos after the first or second cleavage division. In the majority of zygotes (88%) the expected triploidy was confirmed, whereas only 14% of embryos had solely triploid cells. Therefore it is concluded that after tripolar cleavage division, many different types of mosaicism may originate from irregular chromosome distributions. Since the findings in individual blastomeres in embryos resulting from multipronuclear zygotes do not reflect the genetic content of the whole embryo, these embryos are less suitable in a model system for preimplantion diagnosis. The distribution of the sex chromosomal types (XXX, XXY, and XYY) confirmed theoretical expectations. Since in abortion material or in liveborn triploidy cases, the XYY karyotype is hardly ever observed, this indicates that most likely the 69,XYY karyotype has a very high embryonic mortality. PMID- 1617255 TI - Identifying sources of bacterial endotoxin contamination in an in vitro fertilization (IVF) culture environment. PMID- 1617256 TI - Early pregnancy in human may not be associated with mild thrombocytopenia. PMID- 1617257 TI - Midazolam-fentanyl sedation in conjunction with local anesthesia during oocyte retrieval for in vitro fertilization. PMID- 1617258 TI - Relation between antisperm antibodies and the rate of fertilization of human oocytes in vitro. AB - To clarify further the role of antisperm antibodies in in vitro fertilization, the occurrence of antisperm antibodies on ejaculated sperm and in sera was determined by the immunobead binding assay in 67 couples after an unsuccessful in vitro fertilization cycle. Antisperm antibodies in maternal sera were associated with a failure of oocyte fertilization (P less than 0.02) or with fertilization of only 9-19% of the oocytes (P less than 0.01) in vitro. Antisperm antibodies were detected in sera from 13 of 24 women (54.2%) where no fertilization occurred, 9 of 14 women (64.3%) where less than 20% of the oocytes fertilized, and 3 of 19 women (15.8%) where greater than 40% of the oocytes fertilized. Antisperm antibodies in these sera were mostly IgG and directed against the sperm tail. Antibodies on the surface of ejaculated motile sperm were also associated with a low (9-19%) fertilization rate (P less than 0.01). Sperm-bound antibodies were detected in 2 of 24 men (8.3%) where no fertilization occurred, 5 of 14 men (35.7%) where less than 20% of the oocytes fertilized, and 0 of 19 men where fertilization was greater than 40%. Sperm-bound antibodies were mainly IgA and were tail-directed. Antisperm antibodies in sera of males were not related to the rate of fertilization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617259 TI - European developments in complementary medicine. AB - Complementary therapies are becoming increasingly integrated into nursing care. As more nurses adopt these practices, there is a greater need to standardize education in line with European directives to ensure safe, research-based practice. PMID- 1617260 TI - Nurses fear contact with HIV-infected patients. PMID- 1617261 TI - Looking towards the community. PMID- 1617262 TI - AIDS: fear of contagion among nurses. AB - The current moral panic about HIV/AIDS and the theories of deviance that go with it are not a new phenomenon. People expect nurses to know all about HIV/AIDS, but many experience the same fears and ignorance as the public. Empathy is crucial in the nurse/patient relationship and unfavourable attitudes lead to less than optimal care. There is a need to cultivate non-judgmental attitudes towards the care of people infected with HIV. This requires systematic and sensitive educational programmes. As most patients are nursed at home, it is the responsibility of the Government and educational bodies to strengthen the knowledge base of community nurses. The WHO's global programme on AIDS emphasizes the scope of education and promotes worldwide exchange of information and non discriminatory policies. PMID- 1617263 TI - Specialist practitioners for people with learning disabilities. AB - Recent developments occurring within the nursing profession have signalled the need for an introspective review of the role and function of nursing practice in each speciality. Learning disabilities is no exception. PMID- 1617265 TI - Assessment of head-injured children. AB - Adult neurological scales do not always assess conscious levels in head-injured children accurately. A new scale, the Pinderfield scale, has been introduced into the Major Injuries Unit in Birmingham and has found a favourable reception with nurses. PMID- 1617264 TI - Therapeutic use of play in hospital. AB - Children can suffer much anxiety and stress on entering the hospital environment. Play therapy, in all its forms, can help to alleviate such stress, and facilitate a smoother adjustment to the new and potentially frightening surroundings. PMID- 1617266 TI - A system for delivering care. AB - Despite partners and relatives providing care prior to a hospital admission, all too often they are not involved or informed about the treatment process during a patient's stay in hospital. The primary nurse system is an effective way of delivering care within the mental health framework. The primary nurse is responsible and accountable for the patient throughout his/her stay in hospital. Peplau's model of nursing care concentrates on the development of the nurse patient relationship. Care plans should be negotiated with the patient. Care plan meetings are useful for discussing problems, receiving feedback and for supporting colleagues. Family meetings are essential so that the main carer's continuing involvement in care can be acknowledged. PMID- 1617267 TI - PREPP: from novice to expert. AB - There are similarities between the recommendations of PREPP for a future education structure and the Dreyfus skill acquisition model. A model combining the stages of PREPP and Benner is suggested here. PMID- 1617268 TI - When is a prank not a prank? PMID- 1617270 TI - How to apply for a job. AB - In the previous article of this series we considered the need for career planning when making a job change in order to be successful in the current competitive climate. This article aims to assist you with the next stage and will examine job selection, the informal visit and the application form. PMID- 1617269 TI - Not for resuscitative treatment. AB - The nurse is accountable for her actions. A defence of 'obeying orders' will not always be acceptable. Decisions made by mentally competent adults prevail. A living will is not recognized in the English legal system. Relatives do not have the legal power to make treatment decisions on behalf of a mentally incapacitated adult but their views should be sought. The practitioner must act in the patients' best interests but this does not mean that life should be preserved regardless of quality. PMID- 1617271 TI - Assessment of staff appraisal systems. AB - Staff need regular assessments so that job satisfaction, training and good quality services can be ensured. The health service is currently implementing various types of staff appraisal systems which must be carefully tailored to different settings and needs. PMID- 1617272 TI - Audit commission: homeward bound. PMID- 1617273 TI - Patient advocacy: what does it really mean? PMID- 1617274 TI - Breast reconstruction following mastectomy. AB - Plastic surgery techniques remain a mystery to general nurses. The aim of this article is to give insight into the varying methods of breast reconstruction following mastectomy and the associated nursing management and psychological support. PMID- 1617275 TI - Understanding shock. AB - Shock is a life-threatening condition requiring skillful observation and intervention. It is therefore essential for nurses to understand the physiological processes associated with different types of shock and the nursing management of shocked patients. PMID- 1617276 TI - Respite care: challenging tradition. AB - Respite care is frequently provided within a hospital setting and such a service is likely to increase due to community care policies. Nurses need to challenge traditional assumptions on which respite care is based in order to provide a more flexible service. PMID- 1617277 TI - Tissue expansion. AB - Tissue expansion has become a popular method of reconstructive surgery over the last few years and is used to reconstruct a wide range of defects. This article aims to outline the technique and results of tissue expansion on the plastic surgery unit in Bradford. PMID- 1617278 TI - Erythema multiforme. AB - The control of anxiety and pain by combining patient involvement with effective nursing and medical therapy is of paramount importance when caring for the conscious critically ill patient. Early intervention with particle flotation therapy increased patient comfort, prevented further excessive skin loss and promoted healing of new epidermis. Nutritional support using total parenteral nutrition can help to reduce the incidence of sequelae such as immuno compromization, pulmonary tissue oedema and impaired wound healing. Effective infection control measures aimed at preventing excessive colonization of the skin helps to promote the development of new healthy epidermis. Multidisciplinary care incorporating nursing, medical and physiotherapy disciplines is all important in delivering effective critical care. PMID- 1617279 TI - Preceptorship and PREPP. AB - The transition from student to qualified practitioner is a difficult time for nurses. In order to facilitate a less traumatic change in role and status, the UKCC has advocated a period of support under the guidance of preceptors. PMID- 1617280 TI - Punishing AIDS with specialization. PMID- 1617281 TI - Advocacy: what the future holds. AB - The author offers a personal view of the importance of the advocacy role for nurses and highlights problems that may arise as a result of changes in the National Health Service. PMID- 1617282 TI - How to compile a curriculum vitae. AB - The previous article in this series tackled the best way to apply for a job. Increasingly, employers request a curriculum vitae as part of the application process. This article aims to assist you in compiling a c.v. by discussing its essential components and content. PMID- 1617283 TI - Quality assurance: the shape of things to come. AB - Quality assurance is a systematic approach to the delivery of consistent, high quality services. It requires the implementation of quality systems based on international quality standards. Modern quality practice has yet to be addressed within healthcare. PMID- 1617284 TI - The winds of change: psychiatric nursing in Czechoslovakia. AB - This article examines the current state of psychiatry and psychiatric nursing within the Czechoslovakian Republic and is the result of the author's invitation to teach on the first Postgraduate Diploma in Cognitive Behavioural Psychotherapy run in Czechoslovakia. PMID- 1617285 TI - A contribution to the model of biliary infection in rats. AB - The model of biliary tract infection induced in rats given suspension of E. coli into the bile duct is described. To prevent leakage of microorganisms after the administration, a temporary ligation of the bile duct followed. Contemporary groups of sham-operated and control rats (given saline by intrabiliary injection) were compared to assess the significance of the changes. The effect of biliary infection was concentration dependent. If 0.1 ml of the concentration containing 10(2), 10(3) and 10(6) colony-forming units/ml was injected, the mortality of rats reached 8%, 57% and 65%, respectively within 24 h. Blood and bile cultures from all dead animals grew E. coli. To evaluate the effect of chronic biliary infection, the concentration of 10(2) colony-forming units/ml was used. Serum concentrations of total and conjugated bilirubin, cholesterol and creatinine, activities of S-alanine-aminotransferase, S-aspartate-aminotransferase, alkaline phosphatase, the count of leucocytes in blood, total body weight with weight of the liver were investigated on days 1, 4 and 12 after the treatment. The results showed: an increase in leucocytes (21 +/- 4.2 10(9)/l, p less than 0.02 vs control animals) on day 4, an augmentation of serum cholesterol on day 1, (2.1 +/ 0.9 mmol/l, p less than 0.02 vs control animals), the presence of E. coli in blood on day 1 and its persistence in the bile on days 1, 4 and 12. Except the bile, all of the other symptoms were reversible by day 12. PMID- 1617286 TI - Inhibition of ACAT activity after 7-oxo-PGI2 treatment in cholesterol-fed rabbits. AB - It has been supposed that prostacyclin (PGI2) and its analogues have important antiatherogenic effects. The aim of this work was to test the effect of PGI2 and 7-oxo-PGI2- (a stable analogue of PGI2) (6) treatment on the acyl CoA: cholesterol-acyltransferase (ACAT) activity in the aortic wall of rabbits. The rabbits had been previously fed with cholesterol and treated with PGI2 and 7-oxo PGI2 intravenously. Cholesterol feeding increased ACAT activity compared to the control group which was not fed with cholesterol: 16.84 nmol/mg prot./h and 10.03 nmol/mg prot./h, respectively. PGI2 treatment of the cholesterol fed group did not cause a significant decrease, while 7-oxo-PGI2 treatment significantly decreased aortic ACAT activity compared to the cholesterol-fed control group; 14.31 nmol/mg prot./h; 11.53 nmol/mg prot./h and 16.84 nmol/mg prot./h, respectively. The decrease found in the ACAT activity after PGI2 and 7-oxo-PGI2 treatment are new data for the protective effect of these agents against atherosclerosis. PMID- 1617287 TI - Histomorphometry of focal myocardial lesions by means of the automatic image analysis. AB - There is an urgent necessity to objectify focal myocardial lesions (fml) before structural changes in muscle cells can be seen light microscopically. Therefore the succinodehydrogenase (SDH) reaction was chosen because it reliably demonstrates the decrease in aerobic capacity already in structurally unchanged cells and distinguishes the latter from the SDH-negative structures. A combined planimetric and densitometric procedure was developed to measure the area density of fml and their 2 constituents mentioned as well as to evaluate the SDH activity in fml and its decrease in muscle cells using the automatic image analysing system QUANTIMET. The verification tests show that both the area density and extinction can be reliably determined with acceptable measuring errors unless the area density is too low. The results of interobserver and repeatability tests are satisfying. PMID- 1617288 TI - Carcinogenicity testing of some constituents of black pepper (Piper nigrum). AB - In mice, injection of safrole, tannic acid or methylcholanthrene (MCA) during the preweaning period induced tumors in different organs. Safrole and tannic acid (constituents of black pepper) were weak carcinogens when compared with MCA which was used as a carcinogenic control substance. Force feeding of d-limonene (one of the pepper terpenoids) for a long time to the mice which were injected with any of the above 3 substances reduced their carcinogenic activity, while force feeding of piperine (one of black pepper alkaloids) was ineffective. PMID- 1617289 TI - Induction of mitochondrial alterations ex vivo in skeletal muscle. AB - The ultrastructural alterations of mitochondria were studied, following a fixation delay of 45 min, in the normal type II red muscle fibres of pigeon semimetapatagialis muscle. These muscle fibres, were devoid of myofibrillar degeneration; however, their mitochondria showed derangement. The latter included irregular orientation and loss of cristae, and clearing of the matrix. Some mitochondria showed myelin figures of varying complexity in the subsarcolemmal areas as well as in the interior of muscle fibres. These alterations bear striking resemblance to that seen during some lysosomal formation. The significance of these observations is discussed. PMID- 1617290 TI - Primary phase of hepatocytic autophagocytosis under ischaemic conditions. AB - Increased autophagocytosis in hepatocytes was found in response to conditions of ischaemia/hypoxia. Initial stages proved to be recordable. These were found to become manifest through the formation of phospholipid membrane structures, approximately 5 nm in width, coalescing in circular formations with vesicular extensions. They may further develop to form multilayer myelin structures. Enveloped cytoplasmic regions and organelles were unchanged, at the beginning, and subsequently coalesced typically into autophagolysosomes and autophagic vacuoles. Verification will be necessary to find out if these initial stages occur only in response to hypoxia or constitute a phenomenon of general validity. PMID- 1617291 TI - Comparative studies on the effects of aminoglutethimide on hamster and rat adrenal cortex. AB - Adult female, intact or steroid suppressed hamsters were treated twice daily with 7 mg aminoglutethimide phosphate (AG) for 5 days while intact female rats received 14 mg AG per injection. AG resulted in an increase in adrenal gland weight of both hamster and rat. In the hamster AG had no effect on the amount of lipid droplets while in the rat a slightly higher number of fine lipid vacuoles was seen. In the hamster, enlargement of the gland was due to hyperplasia of the zona reticularis cells while in the rat the number of glomerulosa and fasciculata cells increased. AG had no effect on the adrenal cortex of steroid suppressed hamsters. The serum cortisol level was markedly higher in AG-treated hamsters while the corticosterone level was notably lower in AG-administered rats. In both hamsters and rats, AG-treatment did not change the serum ACTH level. Thus the study demonstrated different responses of the hamster and rat adrenal cortex to AG. PMID- 1617292 TI - An ultrastructural study of hydrogen peroxide production by cultured fetal and neonatal rat lung cells exposed to hyperoxia. AB - Hydrogen peroxide production in organotypic cultures of fetal and newborn rat lung cells has been investigated using an ultrastructural histochemical method, in which the quantity and location of an electron-dense reaction product derived from the interaction of cerium chloride and hydrogen peroxide was detected. Hydrogen peroxide was present in fetal cell cultures exposed to hyperoxia (50% oxygen) compared to controls maintained in 10% oxygen. This increase could be limited by incubation of cultures with ascorbic acid and preincubation with dexamethasone. On the other hand, in newborn rat lung cell cultures, less hydrogen peroxide was identified in cultures including those exposed to hyperoxia (50% oxygen). PMID- 1617293 TI - Thickening of the glycocalyx during methotrexate induced small intestinal mucosal atrophy in the rat. AB - In this study, the morphology of the glycocalyx of small intestinal enterocytes in the rat was investigated after the induction of mucosal atrophy by methotrexate (MTX) in 18 Wistar rats. On the 2nd, 4th and 6th day after the intraperitoneal administration of MTX, a group of 6 rats was sacrificed and tissue specimens taken at the level of the Treitz' ligament were post fixed in a mixture of 2.0% watery osmiumtetroxide and 1.5% potassium-ferrocyanide to enhance visibility of glycoconjugates and processed for electron microscopy. In the control rats, the glycocalyx was hardly visible on the villous enterocytes, but rather conspicuous on the enterocytes in the crypts. On the second day after injection of MTX, the glycocalyx of the villous enterocytes was more pronounced but on the crypt enterocytes it resembled that of control animals. On the 4th day after MTX administration, a striking reduction and shortening of microvilli of villous enterocytes was seen, together with very pronounced glycocalyces, while crypt cells possessed well developed cell coats. On the 6th day after the injection of MTX, the glycocalyx of both villous and crypt cells appeared almost normal again. PMID- 1617295 TI - Recession busters! PMID- 1617294 TI - Biochemical and morphological changes in rat brain synaptosomes after exposure to normobaric hyperoxia in vivo. AB - Adult rats were submitted to normobaric hyperoxia for 1 to 24 h, then the brain synaptosomes were isolated and their metabolic and morphologic properties were studied. Hyperoxia lasting 1-2 h significantly increased the content of thiobarbituric acid-reactive material (TBAR) and decreased the level of protein thid groups. During the next 5-8 h of hyperoxia SH groups as well as TBAR content became almost normal, reflecting adaptation of the animals to an elevated oxygen tension. After 24 h of hyperoxia a maximal increase in the TBAR content and parallel fall in protein thiol groups were noted. Simultaneously, significant morphological differences between control synaptosomes and synaptosomes isolated from rats exposed to 24 h oxygenation were observed in electron microscopy. The high-affinity dopamine uptake in hyperoxic synaptosomes was significantly increased in all experimental groups. A specific high sensitivity of the dopamine uptake system in synaptoplasmatic membranes to the free radical modification of the membrane structure is suggested. PMID- 1617296 TI - More for their money! PMID- 1617298 TI - The product payoff. PMID- 1617297 TI - Time is money. PMID- 1617299 TI - RNA binding proteins, splice site selection, and alternative pre-mRNA splicing. PMID- 1617300 TI - RPC10 encodes a new mini subunit shared by yeast nuclear RNA polymerases. AB - Yeast RNA polymerases A, B, and C share five small subunits, two of which, ABC10 alpha and ABC10 beta, comigrate on SDS polyacrylamide gels. The gene encoding ABC10 alpha, RPC10, was isolated based on microsequence data. RPC10 is a single copy gene localized on chromosome VIII. It codes for a very basic protein of only 70 amino acids, which contains a zinc binding domain of the form CX2CX13CX2C. Deletion of its gene indicated that, despite its very small size, the ABC10 alpha subunit is essential for yeast cell viability. ABC10 alpha and ABC10 beta have little sequence similarity. PMID- 1617301 TI - Identification of novel steroid-response elements. AB - A rapid method for defining novel steroid-responsive elements has been developed. Large libraries of degenerate oligonucleotides were analyzed using a yeast-based screen to identify estrogen-responsive DNA sequences. From a library of 40,000 recombinants, seven estrogen-responsive clones were identified. When sequenced, these elements showed remarkable diversity and were different from the consensus vitellogenin A2 ERE. One surprising result was the presence of the two half sites as direct repeats in some of the clones. This implies that in vivo estrogen receptor can bind and transactivate yeast genes through response elements in which the two half sites align as direct repeats. This protocol requires no purified protein and specifically selects for functional response elements. It has a wide application in the study of any transcription factor/DNA interaction. PMID- 1617302 TI - Four sarcomeric myosin heavy chain genes are expressed by human fetal skeletal muscle cells differentiating in culture. AB - Expression of four sarcomeric myosin heavy chain (MHC) genes was examined in continuously passaged human fetal (18-22 week) skeletal myoblasts and in myoblasts induced to differentiate by low mitogen medium. Although embryonic MHC mRNA predominated at all time points following induction, three additional MHC genes were expressed at lower levels. These consisted of perinatal, slow, and fast skeletal MHC genes. Temporal regulation of MHC gene expression was observed. In myoblasts and early induced cultures, embryonic and fast transcripts were detected, accompanied in later induced cultures by the accumulation of perinatal and slow MHC transcripts. In situ hybridization analysis of uninduced cells revealed that sarcomeric MHC transcripts originated from a small population of spontaneously fused multinucleated cells. Taken together, these observations demonstrate that human fetal myoblasts induced to differentiate in culture execute a developmental program that includes temporally regulated expression of four distinct sarcomeric MHC genes. PMID- 1617303 TI - Developmental changes in the methylation status of regulatory elements in the murine alpha 1(I) collagen gene. AB - Regulatory elements contributing to the tissue-specific regulation of the murine alpha 1(I) collagen (Colla1) gene have previously been identified in its promoter region and first intron. Because several lines of evidence indicate that DNA methylation may be involved in the tissue-specific regulation of Colla1 gene expression, we have analyzed the methylation status of the 5' region of the gene by restriction analysis and a methylation-dependent PCR assay. All sites tested were unmethylated in sperm DNA. The region surrounding the start site of transcription was partially or completely methylated in undifferentiated embryonal cell lines, suggesting that it may be marked by de novo methylation during early embryonic development. In differentiated cells and adult tissues, the Colla1 promoter was completely demethylated in collagen-producing and some nonproducing cells, and partially methylated in other nonproducing cells. The first intron was unmethylated in collagen-producing as well as nonproducing cells. Only sites in the first exon showed an inverse correlation with transcriptional activity, i.e., they were unmethylated in cells that express the gene, but predominantly methylated in cells that do not. Our results indicate that the methylation status of a small area (less than 1 kb) downstream of the Colla1 promoter, but not of the promoter itself or the first intron, may be critical for transcriptional activity of the promoter, presumably through an indirect mechanism. PMID- 1617305 TI - The Women's Health Data Book. A profile of women's health in the United States. PMID- 1617304 TI - The start site of the Acanthamoeba castellanii ribosomal RNA transcription unit. AB - The 39S ribosomal RNA (rRNA) precursor has been isolated from Acanthamoeba castellanii. In vitro capping of the isolated RNA verified that it is the primary transcript and identified the 5' nucleotide as pppA. The position of the 5' coding nucleotide on the rRNA repeat unit sequence was identified using Northern blot, R-loop, and S1 nuclease mapping techniques. Dinucleotide priming of an in vitro transcription system stalled because of low initiating nucleotide concentration revealed that ApA maximally stimulates initiation of transcription. All of these results show that the underlined A in the sequence 5' TATATATAAAGGGAC (RNA-like strand) coincides with the 5' nucleotide of the primary transcript. This identification is compatible with in vitro transcription experiments mapping the promoter for this transcription unit. The initiation sequences of rRNA genes from 14 species are compared, and a weak consensus for the initiator derived: [Formula; see text]. PMID- 1617306 TI - Lipids and cardiovascular disease: do the findings and therapy apply equally to men and women? AB - Dyslipoproteinemia is prevalent in women as well as in men. In both, its consequences--premature atherosclerosis and CAD morbidity and mortality--are more common. Although clinical evidence of the benefits of cholesterol lowering is less abundant in women, it is not entirely absent. As in men, cholesterol lowering in women is associated with a decline in CAD risk and with regression of coronary atherosclerosis. Lipoprotein risk factors have some special characteristics in women. Low-density lipoprotein cholesterol may be a less important risk factor in women, perhaps because estrogen protects the arterial wall against LDL deposition. High-density lipoprotein cholesterol is a better predictor of risk in women than in men. Triglycerides are an independent predictor of CAD risk in postmenopausal women. The effects of endogenous gonadal hormones in life-cycle changes in women is evident. As girls pass through puberty, HDL-C levels do not fall as they do in boys of the same age. In pregnancy, LDL-C, HDL-C, and triglyceride levels all rise. However, LDL-C stays elevated until well after delivery, whereas triglycerides fall to baseline at about the time of delivery, and HDL-C levels begin to fall at about 24 weeks. Interestingly, this fall in HDL-C is not accompanied by a fall in apoA-I levels, implying a change in HDL composition during the latter portion of pregnancy. After menopause, LDL-C levels rise sharply, whereas HDL-C levels decline modestly. Again, this decline in HDL-C is accompanied by a rise in apoA-I levels, implying a change in HDL composition. Diet, weight loss, and exercise are less effective in altering lipoprotein levels in women than in men. The reasons for this are not clear, although it is reasonable to speculate that endogenous gonadal hormones play a role. Genetic dyslipoproteinemia occurs in women, although the effect on CAD rates may be mitigated by the generally higher levels of HDL-C enjoyed by women. Exogenous hormones in the form of OCs and postmenopausal HRT affect circulating lipoprotein levels according to their composition. Generally, estrogens have favorable effects, raising HDL-C and lowering LDL-C levels. Progestins are either neutral or oppose estrogen effects, depending on their dose and androgenicity. Use of modern OCs probably does not adversely affect CAD risk except in combination with cigarette smoking. However, HRT has a strong favorable effect on CAD risk when unopposed estrogen is used, probably due to increases in HDL-C levels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1617307 TI - Obesity and weight gain during adulthood: a health problem for United States women. PMID- 1617308 TI - A report and recommendations from the Jacobs Institute-Mead Johnson Laboratories Symposium on Preventive Health Care for Older Women. PMID- 1617309 TI - Compliance with hormone replacement therapy: are women receiving the full impact of hormone replacement therapy preventive health benefits? PMID- 1617310 TI - Screening for gynecologic and colorectal cancer: is it adequate? PMID- 1617311 TI - Why aren't older women getting mammograms and clinical breast exams? PMID- 1617312 TI - What is the best strategy for autotransplants in cancer? PMID- 1617313 TI - Immune responses to chronic myeloid leukaemia. AB - The negative impact of donor marrow T lymphocyte depletion on relapse of chronic myeloid leukaemia (CML) following bone marrow transplantation strongly suggests that the leukaemia is particularly susceptible to immune regulation. The immune response to CML may be mediated by major histocompatibility (MHC) locus unrestricted natural killer and lymphokine activated killer cells, or by MHC restricted CD4 and CD8 lymphocytes. Interaction with the leukaemia is both by direct cell-contact cytotoxicity, and indirectly via cytokines and growth factors. T4 and T8 lymphocytes recognize a spectrum of minor histocompatibility antigens on the leukaemia cell which may be non-specific, leading to graft-versus leukaemia and graft-versus-host reactions, or present only on myeloid cells leading to a tissue restricted response. The possibility that the P210 protein derived from the BCR/ABL fusion gene on chromosome 22 leads to the presentation via MHC molecules of leukaemia-specific peptide antigens is currently under investigation. Developments in understanding the immune response to CML open up the possibility of developing leukaemia-specific immunotherapy strategies. PMID- 1617314 TI - Treatment of infant leukemia with busulfan, cyclophosphamide +/- etoposide and bone marrow transplantation. AB - Infants with acute leukemia have a poor chance of being cured by conventional chemotherapy. We therefore treated cases of infant leukemia with high dose chemotherapy followed by bone marrow transplantation (BMT). Six suffered from acute leukemia and one from refractory anemia with excess of blasts (RAEB-t). The conditioning regimen consisted of busulfan (BU) and cyclophosphamide (CY), and was intensified by adding etoposide (VP) in four cases. At the time of BMT the children were 4, 5, 12, 13, 13, 14, and 20 months old. Three children were autografted, three received HLA-identical marrow from a sibling donor, and one child received matched unrelated donor marrow. All five children who were grafted in complete (CR) or partial remission (PR) are alive and well in CR 7, 13, 24, 37, and 46 months after allogeneic (two patients) or autologous (three patients) BMT, and 13, 17, 29, 42, and 53 months after initial diagnosis. The child with RAEB-t and the one transplanted in second chemotherapy-resistant relapse of acute non-lymphoblastic leukemia relapsed at 7 and 17 months respectively. The chemotherapy regimen was well tolerated. BU-CY-VP is a promising alternative treatment to regimens including total body irradiation for very young children suffering from acute leukemia. PMID- 1617315 TI - An effective immunomagnetic method for bone marrow purging in T cell malignancies. AB - An immunomagnetic method was developed to purge human bone marrow of malignant T cells, for use in conjunction with autologous bone marrow transplantation in patients with acute lymphoblastic leukemia and lymphoma. Three monoclonal antibodies anti CD2 (BH1), CD5 (BB8) and CD7 (BF12) were used. In model experiments employing MOLT4 cells it was found that with 50-fold excess of immunobeads relative to antigen-positive cells, the use of each antibody alone resulted in a 3.3-3.6 log tumor cell depletion, as assessed in a sensitive and reproducible clonogenic soft agar assay. When all three antibodies were used in a mixture, a purging efficacy of 5 logs was achieved. Two treatment cycles improved these figures to about 4 logs and more than 5 logs. When MOLT4 cells were mixed 1:10 with fresh bone marrow cells the antibody mixture yielded 3.1 and more than 5 log tumor cell depletion with one and two treatment cycles, respectively. This procedure resulted in only an insignificant reduction of the number of CFU-GM and CFU-GEMM progenitor cells. In two patients autotransplanted with purged marrow, the loss of CFU-GM was 37% and 48%, and no tumor cells could be detected by immunocytochemistry after purging. Rapid and sustained engraftment was achieved and both patients remain in complete remission after more than 20 months. PMID- 1617316 TI - Autoantibodies after bone marrow transplantation in children with genetic disorders: relation to chronic graft-versus-host disease. AB - The occurrence of autoantibodies and their relation to chronic graft-versus-host disease (GVHD) have been studied in children, 100 days or more following allogenic bone marrow transplantation (BMT), mainly performed for a variety of genetic disorder. Seventeen of 40 patients had autoantibodies to thyroid microsomes, compared with none of 46 control children of similar age (p less than 0.001). The presence of these antibodies was strongly associated with chronic GVHD (14 of 20 patients), p = 0.001. IgG antibodies to the cytoplasm of squamous epithelial cells were demonstrated in 15 of 36 children following transplantation (p less than 0.001), none being found in 46 normal children. The incidence and titre of these antibodies were significantly higher in patients with chronic GVHD (p = 0.041 and p = 0.019 respectively). Despite there being a significant number of patients with antibodies to nuclei, smooth muscle and gastric parietal cells, these autoantibodies were not related to the presence of chronic GVHD. Although the mechanism of production is not known, antibodies to thyroid antigens and the cytoplasm of squamous epithelial cells may be useful markers for GVHD. PMID- 1617317 TI - Detection of circulating endogenous interleukin-3 in extensive chronic graft versus-host disease. AB - Recent data suggest that activated immune cells and their products are involved in the initiation and progression of graft-versus-host disease (GVHD). To test whether the production of endogenous interleukin-3 (IL-3), a product of activated immune cells, might be an indicator of disease activity in GVHD, we analysed sera of 61 bone marrow transplant (BMT) recipients for IL-3 levels by using an enzyme linked immunosorbent assay. Measurable levels (greater than 25 pg/ml) of endogenous IL-3 were detected in a significant subgroup (5/16 patients, 31.25%) of allograft recipients suffering from extensive chronic GVHD, but not in patients with limited chronic GVHD (n = 6) or in those without signs of chronic GVHD (n = 17). In IL-3 positive patients, IL-3 levels were not associated with pathologic conditions (such as infectious disease) other than GVHD. IL-3 levels were undetectable in disease-free phases preceding severe chronic GVHD. Lower levels of IL-3 were measured in chronic GVHD patients during extensive disease while on high dose steroid medication compared with before and/or after (p less than 0.02). IL-3 was also detected in a small group (2/17) of patients suffering from acute GVHD. IL-3 could neither be detected in syngeneic (n = 3) nor autologous (n = 7) BMT recipients nor in the vast majority (99/100) of healthy controls. Together, measurable amounts of IL-3 are produced in a significant subgroup of patients suffering from extensive chronic GVHD. PMID- 1617318 TI - Total body irradiation with or without lung shielding for allogeneic bone marrow transplantation. AB - From June 1986 to June 1990, 64 patients with leukaemia (25 acute myelogenous leukaemia, 21 acute lymphoblastic leukaemia and 18 chronic myeloid leukaemia) undergoing marrow transplantation were randomized to receive cyclophosphamide (CY) and fractionated total body irradiation (TBI) without lung shielding (n = 33) or CY and fractionated TBI with lung shielding (n = 31, control group) as conditioning. Patients conditioned with TBI without lung shielding received a significantly higher total lung dose compared with the control group (p less than 0.0001). The 3-year leukaemia-free survival for patients receiving TBI without lung shielding is 54 +/- 18% versus 51 +/- 18% for patients receiving TBI with lung shielding (p = ns). There was no significant difference in the probability of leukaemia relapse (22 +/- 18% for TBI without lung shielding versus 24 +/- 18% for control group; p = ns). The probability of interstitial pneumonitis is 15 +/- 14% for TBI without lung shielding and 5 +/- 5% for TBI with lung shielding (p = ns). A higher incidence of lung fungal infection (15 versus 3%) and interstitial pneumonitis (12 versus 3%) has been documented in patients receiving TBI without lung shielding compared with the control group. The results indicate that higher radiation dose to the lung did not increase antileukaemic efficacy of TBI but seemed to be associated with the increased pulmonary toxicity. PMID- 1617320 TI - Autologous blood transfusion for pediatric bone marrow donors. AB - Nine normal bone marrow donors aged 7-166 months (median 69 months) received autologous red cells which had been removed from their marrow harvest after collection. The median volume of marrow removed from the donors was 18.6 ml/kg which was equivalent to a median blood volume loss of 23.3%. Three infant donors were transfused with autologous red blood cells intraoperatively. These cells had been salvaged from the initial marrow aliquot and were transfused while bone marrow harvesting continued. No donors required homologous blood transfusion. This technique is useful for marrow donors in the pediatric age group when preharvest autologous blood collection is not feasible or available. PMID- 1617319 TI - Influence of post-methotrexate folinic acid rescue on regimen-related toxicity and graft-versus-host disease after allogeneic bone marrow transplantation. AB - Thirty-two patients undergoing related-donor bone marrow transplantation (BMT) received cyclosporine (CSP) and methotrexate (MTX) with folinic acid rescue (FAR) as graft-versus-host disease (GVHD) prophylaxis. Fifty consecutive related-donor BMT patients given the CSP/MTX combination without FAR were utilized as historical controls. Patients receiving FAR experienced earlier engraftment, with absolute neutrophil count greater than 0.5 x 10(9)/l at a median of 17 days (vs 21 days in controls, p = 0.002). The day of last platelet transfusion was earlier in the FAR group (median of 14 days vs 17 days in controls, p = 0.01). Compared with the control group, patients receiving FAR had a lower incidence of grade II IV stomatic (53% vs 78%, p = 0.04) and hepatic (25% vs 56%, p = 0.01) regimen related toxicity. In the FAR group, 70% required total parenteral nutrition vs 92% of controls (p = 0.02). Broad-spectrum antibiotics were given to FAR patients for a median of 21 days (vs 23 days in controls, p = 0.09). The incidence of grade II-IV acute GVHD was similar in the FAR and control populations (45% and 35%, respectively, p = NS) as was the incidence of chronic GVHD (62% vs 55%, respectively, p = NS). Estimated event-free survival is 59% for FAR patients (median follow-up 64 weeks) and 58% for controls (median follow-up 109 weeks, p = NS). FAR reduces regimen-related toxicity in patients receiving CSP/MTX acute GVHD prophylaxis without significantly influencing GVHD incidence or event-free survival. PMID- 1617321 TI - Regulation of tumor necrosis factor-alpha production and gene expression in monocytes. AB - Tumor necrosis factor-alpha (TNF-alpha), produced predominantly by activated monocytes/macrophages, inhibits leukemic cell growth and may contribute to a graft-versus-leukemia effect after marrow transplantation. We examined the recombinant cytokines interferon (IFN)-alpha, IFN-gamma, granulocyte- macrophage colony-stimulating factor (GM-CSF), and macrophage colony-stimulating factor (M CSF), alone or in combination, for their ability to induce monocytes from normal donors and patients after marrow grafting to express TNF-alpha mRNA and secrete TNF-alpha bioactivity. Monocytes were isolated from peripheral blood by Percoll separation of E-rosette-negative cells, and cultured with cytokines under non adherent, endotoxin-free conditions. TNF-alpha transcripts were undetectable in freshly isolated monocytes from normal donors. Only the combination of IFN gamma/GM-CSF was consistently capable of inducing substantial TNF-alpha mRNA transcript levels and protein secretion. Levels of TNF-alpha transcripts induced by IFN-gamma/GM-CSF were maintained for at least 36 h, in contrast to lipopolysaccharide (LPS) stimulation which caused TNF-alpha mRNA levels to peak after 2 h and decline rapidly thereafter. IFN-gamma/GM-CSF was also capable of inducing a prolonged (at least 48 h) secretion of TNF-alpha bioactivity. In contrast, greater than 80% of the total TNF-alpha bioactivity secreted by LPS stimulated monocytes was secreted in the first 8 h. When monocytes were incubated with IFN-gamma alone ('priming'), washed and then exposed to GM-CSF, both TNF alpha mRNA expression and TNF-alpha protein production occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617322 TI - Neutropenic enterocolitis associated with autologous bone marrow transplantation. AB - Fatal neutropenic enterocolitis was seen in a patient undergoing autologous bone marrow transplantation for non-Hodgkin's lymphoma. Excessive drug action due to a mildly diminished creatinine clearance could have contributed to the pathogenesis. Computed tomographic scanning and ultrasonography demonstrated pneumatosis of the gastrointestinal tract, but the disease had become extensive by then. Necrotizing enterocolitis should be suspected early in a granulocytopenic patient with abdominal pain and diarrhea or vomiting. Aggressive surgical or medical management may avoid a fatal outcome. PMID- 1617323 TI - An HIV positive haemophiliac with acute lymphoblastic leukaemia successfully treated with intensive chemotherapy and syngeneic bone marrow transplantation. AB - A 26-year-old HIV positive severe haemophiliac developed Burkitt-type acute lymphoblastic leukaemia with intracranial involvement. He underwent standard combination therapy, and entered complete remission. Syngeneic bone marrow transplantation (BMT) was undertaken; the donor was also HIV positive. The patient died 18 months from transplant of isolated intracranial relapse, with no evidence of systemic relapse. Unlike other types of non-Hodgkin's lymphoma, Burkitt's type occurs in HIV positive patients with relatively normal CD4 cell counts. Remission can be achieved using intensive chemotherapy, and since these patients may otherwise have a reasonable life expectancy, BMT may be appropriate. PMID- 1617324 TI - Interaction between cyclosporin A and anticonvulsants. Bone Marrow Transplantation Team. PMID- 1617325 TI - Evils in the private practice of psychotherapy. AB - The private, and especially solo, practice of psychotherapy often poses conflicts of interest between patient and therapist, which, because of the field's ambiguities and equivocal guidelines, may tend to be resolved in favor of the therapist and to the detriment of the treatment. The author delineates these potential conflicts so that awareness and training can minimize their pernicious effects. PMID- 1617326 TI - Assessing boundary violations in psychotherapy: survey results with the Exploitation Index. AB - The usefulness of the Exploitation Index (Epstein & Simon, 1990) was evaluated in a survey of psychiatrists. Forty-three percent of the respondents indicated that at least one item alerted them to behavior they thought could have been counterproductive to treatment. Twenty-nine percent found that they were stimulated to make specific changes in future treatment practice. On average, female respondents endorsed fewer boundary violations than males. PMID- 1617327 TI - Eating disorders in the 1990s: clinical challenges and treatment implications. AB - Eating disorders are, and most likely will continue to be, a ubiquitous clinical and therapeutic challenge. The high morbidity and mortality rate of anorexia nervosa and bulimia nervosa presents a major psychiatric problem in contemporary mental health treatment. The author briefly reviews the importance of comorbidity and sexual abuse in this patient population, the special problems of males with eating disorders, salient countertransference paradigms, the role of masochism, and the impact of projective identification on the treatment process. She describes the major clinical considerations, treatment strategies, and psychodynamic issues, giving particular attention to the role of extended inpatient treatment for the refractory patient. The author urges treaters to be emotionally available to these patients, who struggle with the interpersonal dilemma of maintaining separateness while establishing mature connectedness. PMID- 1617328 TI - Depression and conduct disorders in children and adolescents: a review of the literature. AB - The psychological literature presents three explanatory models of the relationship between childhood or adolescent depression and conduct disorders: (1) a direct causal relationship; (2) an indirect causal relationship, involving a third set of variables (i.e., personality disorders and developmental deficits); and (3) the "final common pathway" hypothesis, which derives a relationship ex post facto. Each of these models has dominated the literature at a different period, each was affected by different research purposes, and each in turn influenced further research. The author describes and critiques the three models and concludes with suggestions for further exploration in the areas of theory and etiology, research, diagnosis, and treatment. PMID- 1617329 TI - Transitional objects as objectifiers of the self in toddlers and adolescents. AB - Particular transitional experiences--such as moving through space or into sleep- may evoke the use of transitional objects by children in their second year of life. Toddlers still identify objects by their position in space. Thus, at the point in development when a child first synthesizes a cohesive ego, literal transition of the child from one place to another can disrupt incipient confidence in a sense of self. An object representing the self that the child transports to the new place can reinforce a sense of personal control and personal continuity. Such use, which the author terms self-objectification, explains why the presence or absence of the mothering caregiver is not necessarily the determining factor in whether a child employs a transitional object. Later in life (e.g., adolescence), when identity issues again become crucial, concrete transitional mechanisms can again help reduce anxiety. The author uses case material from the treatment of three adolescents to illustrate this phenomenon. PMID- 1617330 TI - Addiction as a form of perversion. AB - Psychoanalytic treatment of addiction is often ineffective because therapists fail to recognize addiction as a discrete disorder. The author reviews psychoanalytic theories of addiction and presents an alternative concept comprising biological, behavioral, and psychological characteristics. She compares the structural similarities between addiction and perversion and describes the use of the addictive substance as a fetish object. Finally, she discusses the implications of psychoanalytically oriented treatment and advocates a multimodal treatment approach. PMID- 1617331 TI - Transference and countertransference implications of psychotherapy conducted in a foreign language. AB - Psychotherapy possesses distinct characteristics when it is conducted in the patient's native language if this language is not also the therapist's mother tongue, a fairly common situation with immigrant patients. The choice of a native therapist, who speaks the foreign patient's mother tongue but lacks perfect command of that language, involves some specific implications, including conflicts around issues of control, regression, and separation-individuation. The author presents several clinical vignettes to demonstrate these conflicts as they are manifested in the therapeutic encounter, especially in various transferential and countertransferential phenomena. He suggests that the therapist-patient relationship in such cases has significant positive therapeutic implications that can facilitate rather than complicate treatment. PMID- 1617332 TI - Microbial superantigens and autoimmune disease. PMID- 1617333 TI - Heat shock proteins and arthritis. PMID- 1617334 TI - Receptor-targeted immunotherapy. AB - Modern techniques of genetic engineering have led to the development of novel receptor-targeted immunotherapies for human diseases. These new approaches include mAbs to the CD4+ subset of T cells, immunotoxins for CD5+ T cells, a diphtheria toxin coupled to IL-2, and antibodies to specific TCRs. Additional approaches include a specific IL-1 receptor antagonist and soluble receptors for IL-1 or TNF. Although initially promising, these new approaches to altering immune and inflammatory events need to be thoroughly and carefully evaluated in further clinical trials in human diseases. Perhaps these novel forms of receptor targeted immunotherapy will eventually prove to be most effective when employed in combination with more conventional anti-inflammatory and immunosuppressive medications. PMID- 1617335 TI - Blood cholesterol: who to test. 2. PMID- 1617336 TI - Organization of endoscopy training. PMID- 1617337 TI - Neonatal extracorporeal membrane oxygenation. AB - Extracorporeal membrane oxygenation is an effective life support technique that has had most success in the treatment of neonatal cardiopulmonary failure. We review the technique and its potential indications and present the latest UK and worldwide survival data. PMID- 1617338 TI - Psychiatric disorders in Parkinson's disease. AB - Parkinson's disease is associated with a wide variety of psychiatric syndromes. Advances in the neuropathology and neuropharmacology have not been applied to the associated psychiatric disorders due to complex interactions between social, psychological and pathological variables. PMID- 1617339 TI - Churg-Strauss syndrome. AB - The presentation of Churg-Strauss syndrome is most distinctive, permitting diagnosis on clinical grounds. It is a phasic disorder with allergic rhinitis and asthma initially, often followed by peripheral blood eosinophilia with eosinophilic tissue infiltrates. The vasculitic illness is the life-threatening phase, but it can be effectively suppressed by prompt treatment. PMID- 1617340 TI - Sexually transmitted diseases in pregnancy. AB - Sexually transmitted diseases (STDs), grouped together are one of the most common medical complications of pregnancy. They can have serious adverse effects on the health of both the pregnant mother and her baby. The increasing prevalence of many STDs and the advent of human immunodeficiency virus (HIV)-related problems emphasize the need for STD awareness in the care of pregnant women. PMID- 1617341 TI - Management of fibrosing alveolitis. AB - Fibrosing alveolitis kills half of those who suffer from it within 5 years of diagnosis. Its incidence appears to be increasing and the response to treatment is disappointing. This article explores the reasons why the response to treatment is poor and ways in which new approaches to treatment might be developed. PMID- 1617342 TI - Antibiotic resistance in community-acquired pneumonia. AB - Antibiotic resistance in bacteria is but one of many factors to consider when treating patients with community-acquired pneumonia. Many bacterial resistance patterns are stable, but wide geographical variation, increasing penicillin resistance in pneumococci and ampicillin resistance in Haemophilus influenzae are now being found. The importance of these features and their impact on therapy are reviewed. PMID- 1617343 TI - Talking with children. AB - Talking with children is an enjoyable but often challenging aspect of a doctor's work. It is a two-way process, with verbal and non-verbal communication being equally important. Patience, humour and imagination are major assets. PMID- 1617344 TI - Doctors' working hours and the law. PMID- 1617345 TI - Clinical cases in AIDS. 1. AB - As the human immunodeficiency virus (HIV) epidemic continues there are increasing numbers of patients with HIV-related disease. Doctors studying for the MRCP exam will need to be familiar with the common manifestations of HIV infection and acquired immunodeficiency syndrome. PMID- 1617346 TI - Inhaled anaesthetic agents: from ether to halothane. AB - The introduction of general anaesthesia revolutionized surgical practice. In this workshop and the one that follows in a future issue the evolution and properties of inhalational anaesthetics are reviewed and future developments are considered. Here we look at the period between the introduction of ether and of the first modern agent, halothane. PMID- 1617347 TI - No more dogma to foul the NHS. PMID- 1617348 TI - Obesity and Arizona. PMID- 1617349 TI - Confusion over definitions of TIA and RIND. PMID- 1617350 TI - Three large trials support a role for digoxin in CHF. PMID- 1617351 TI - Relief of upper airway obstruction. PMID- 1617352 TI - Advantages of locating the subclavian vein by IVDSA. PMID- 1617353 TI - Psychosocial influences in schizophrenia. PMID- 1617354 TI - The psychological complications of therapeutic abortion. AB - Psychological or psychiatric disturbances occur in association with therapeutic abortions but they seem to be marked, severe, or persistent in only a minority (approximately 10%) of women. These consist mostly of caseness depression and anxiety. Psychoses are very uncommon, being reported in only 0.003% of cases - most of whom have a history of previous psychiatric illness. Certain groups are especially at risk from adverse psychological sequelae; these include those with a past psychiatric history, younger women, those with poor social support, the multiparous, and those belonging to sociocultural groups antagonistic to abortion. This is not to overlook the fact that, adopting a crisis-resolution framework, subsequent termination of an unwanted pregnancy is itself 'therapeutic'. A better understanding of the nature of the risk factors would enable clinicians to identify vulnerable women for whom some form of psychological intervention might be beneficial. PMID- 1617355 TI - Is there a link between suicide in young men and unemployment? A comparison of the UK with other European Community Countries. AB - Within the context of marked increases in suicide rates in the UK among men between 1974 and 1988, the rate among those aged 15-24 years rose more than that of any other age band. The UK suicide rate among young men also worsened compared with those of most other countries in the EC. Rises in the general male suicide rate were statistically associated with rises in unemployment in most of the EC. PMID- 1617356 TI - Suicide prevention: spreading the gospel to general practitioners. AB - General practitioners were trained in the recognition and treatment of suicide risk either by written text alone or combined with a seminar meeting. They filled in questionnaires before and after training. In the seminar group, knowledge and attitudes changed significantly, while those doctors receiving written material only had similar results to those without training. PMID- 1617357 TI - Psychiatric morbidity in homeless women. AB - The psychiatric status of 70 homeless women from two direct-access hostels in inner-London was assessed. Detailed sociodemographic, psychiatric and physical illness data were also collected, and where possible, verified from psychiatric and general hospital sources. Forty-five women met DSM-III-R criteria for schizophrenia, but few were in contact with the psychiatric services or in receipt of any treatment. PMID- 1617358 TI - A survey of practice at a regional forensic service: what do forensic psychiatrists do? Part I: Characteristics of cases and distribution of work. AB - During a six-month period, 306 psychiatric assessments were recorded prospectively on specifically designed schedules. There was a skewed distribution towards younger patients, and 78% were male. Just over half were seen for a court report, one-third of cases came from solicitors, and in two-thirds the request was merely for advice. Secure care was only sought in 15%. In nearly two-thirds an offence had precipitated the referral. Half were seen in prison. The majority had a history of dangerous behaviour and one-fifth were regarded as a sexual risk to others. Only one-third had not previously seen a psychiatrist. A personality disorder was diagnosed in 41%, but only 6% were considered to be psychopaths. These and other findings are discussed to help give an insight into the service. PMID- 1617359 TI - A survey of practice at a regional forensic service: what do forensic psychiatrists do? Part II: Treatment, court reports and outcome. AB - Nearly half of those seen in a forensic service were offered some form of help, but it did not reliably match that requested. In 63% of court reports there was no specific treatment recommendation, but where there was, it was likely to be accepted. Only one-third of all out-patients completed the treatment offered -40% of the lapses were due to imprisonment. One-third of out-patient treatments were conducted under conditions of probation orders, and this form of compulsion was associated with a significantly higher number of completed treatment plans. Personality disorder was also associated with more treatment completions. These and other findings are discussed to assist in an understanding of the service. PMID- 1617360 TI - Links between early post-partum mood and post-natal depression. AB - The Edinburgh Postnatal Depression Scale (EPDS) was used to rate 217 patients at five days and six weeks post-partum. There was a highly significant positive correlation between the two scores, together with similar symptom profiles. Of the 25 women who suffered post-natal depression (6-week EPDS score greater than or equal to 13), 17 had similar symptoms in the first week post-partum (5-day EPDS score greater than or equal to 10). Low birth weight of the baby, delivery by Caesarean section, a delivery much more difficult than expected, and bottle feeding were all significantly associated with a high EPDS score in the first week post-partum. Bottle feeding and delivery by Caesarean section were the only factors associated with depression at the sixth week. A recollection of low mood after a previous birth was also associated with post-natal depression after the current birth. This, together with an EPDS score of 13 or more at five days post partum, increased the risk of post-natal depression at six weeks 85-fold. PMID- 1617361 TI - Feelings of guilt in major depression. Conceptual and psychometric aspects. AB - A new scale for the evaluation of feelings of guilt is described. Two types of guilt feeling were of potential interest: 'delusional' guilt or shame (experienced in relation to one's actions), and 'affective' guilt (a more general feeling of unworthiness). Reliability and validity analyses for the first (15 item) version of the scale were performed in three separate and contrasting clinical samples. The second and final (seven-item) version was tested in another sample of major depressives and in normal controls. The HRSD was used as a measure of severity throughout. The BDI and Widlocher psychomotor retardation scale were also used as external criteria for the seven-item scale. Exploratory factor analysis of this sample yielded two factors--'cognitive/attitudinal' and 'mood/feeling'--of which only the first correlated with scores for psychomotor retardation. It is suggested that these two factors represent two forms of guilt, but that only the former is related to a putative dopaminergic disorder. Guilt scores and measures of severity were not correlated. It is suggested that feelings of guilt should be considered as a behavioural marker for a subtype of depression. PMID- 1617362 TI - The relationship of environmental temperature to the incidence and outcome of schizophrenia. AB - This paper presents new analyses of data from two multicentre studies carried out by the WHO. The morbid risk of developing schizophrenia, as broadly defined by the Determinants of Outcome Study, was positively related to the mean daily range of temperature. The outcome of schizophrenia, as determined by the International Pilot Study of Schizophrenia, was found to be positively related to mean environmental temperature. Further studies are needed to examine the relationship of geographical and climatic variables to schizophrenia in order to complement what is already known about the role of sociocultural factors. PMID- 1617363 TI - The Nithsdale schizophrenia surveys. X: Obstetric complications, family history and abnormal movements. AB - Obstetric histories of 54 schizophrenic patients and 114 siblings were obtained from their mothers and scored using the Obstetric Complications Scale. There were no statistically significant difference in the proportion of schizophrenic patients (35%) and siblings (29%) who had at least one definite obstetric complication. There was no evidence that schizophrenic patients with a history of obstetric complications were less likely to have a first-degree relative with a history of psychiatric illness leading to in-patient care. Schizophrenic patients with a history of obstetric complications were more likely to have drug-induced Parkinsonism. There was a trend for tardive dyskinesia to be more common in those schizophrenic patients with no obstetric complications but a family history of schizophrenia. PMID- 1617364 TI - Specific and non-specific effects of educational intervention for families living with schizophrenia. A comparison of three methods. AB - Three methods of delivering an educational intervention to families living with a schizophrenic relative were compared in terms of their efficacy in improving understanding and promoting family and patient well-being. Relatives receiving education in a group acquired more information than relatives receiving information by post or on video, but these differences were not maintained at six month follow-up. The inclusion of homework assignments did not significantly affect gains in knowledge or any of the non-specific effects observed. The intervention overall led to considerable gains in knowledge, increased optimism concerning the family's role in treatment, and reductions in relatives' stress, which were maintained at follow-up. Fear was reduced in the short-term. Significant improvements in social function were observed at follow-up. The results suggest that the delivery of information, rather than the mode of delivery, is the crucial element in the intervention; however, the additional contextual factors operating in a group may be important if the full potential of education is to be realised. PMID- 1617365 TI - Clinical observation of assessment using the Composite International Diagnostic Interview (CIDI). An analysis of the CIDI Field Trials--Wave II at the St Louis site. AB - Two clinicians scored the ICD-10 Research Criteria Checklist either while observing or after administering CIDI interviews to a sample of 20 subjects. Overall diagnostic concordance between clinical and CIDI assessments was found to be good (overall kappa = 0.77). Assessment of the specific diagnoses could be done only for the three most commonly represented in the studied sample: anxiety/phobic disorders (kappa = 0.73), depressive disorders (kappa = 0.78), and psychoactive substance use disorders (kappa = 0.83). While the lack of independence of the two assessments and the small, non-randomly selected sample might have exaggerated the concordance, this study shows that the CIDI provides all the data needed to score diagnoses in the ICD-10 nomenclature, as indicated by the small number of questions clinicians needed to ask following completion of the CIDI. PMID- 1617366 TI - The Explanatory Model Interview Catalogue (EMIC). Contribution to cross-cultural research methods from a study of leprosy and mental health. AB - The Explanatory Model Interview Catalogue (EMIC) has been developed to elicit illness-related perceptions, beliefs, and practices in a cultural study of leprosy and mental health in Bombay. Leprosy is an especially appropriate disorder for studying the inter-relationship of culture, mental health and medical illness because of deeply rooted cultural meanings, the emotional burden, and underuse of effective therapy. Fifty per cent of 56 recently diagnosed leprosy out-patients, 37% of 19 controls with another stigmatised dermatological condition (vitiligo), but only 8% of 12 controls with a comparable non stigmatised condition (tinea versicolor) met DSM-III-R criteria for an axis I depressive, anxiety or somatoform disorder. Belief in a humoral (traditional) cause of illness predicted better attendance at clinic. PMID- 1617367 TI - Training community psychiatric nurses for psychosocial intervention. Report of a pilot study. AB - Community psychiatric nurses were trained to deliver psychosocial intervention to clients with a diagnosis of schizophrenia living at home with relatives. The training package consisted of family assessment, health education, and family stress management strategies. In a 'quasi-experimental' design, a sample of families (n = 54) were recruited to either a control or experimental condition and followed up for 12 months. A number of favourable outcomes were observed in the experimental group, including improvements in the client's target symptoms, personal functioning, and social adjustment. Relatives' satisfaction with services increased and reports of their own minor psychiatric morbidity improved. PMID- 1617368 TI - Autosomal dominant gene transmission in a large kindred with Gilles de la Tourette syndrome. AB - A multiplex kindred ascertained through a single proband with GTS has been systematically investigated with standardised diagnostic instruments for other cases of GTS and related disorders. Complex segregation analysis supported the hypothesis that a single major gene inherited in autosomal dominant fashion but with incomplete penetrance contributed most of the variance in the liability to develop GTS and related disorders. This result is consistent with previous segregation analyses which have employed different methods of ascertainment, and tends to confirm that a proportion of GTS is due to a dominant gene and is suitable for investigation with genetic markers for linkage analysis. PMID- 1617369 TI - The meaning of insight in clinical psychiatry. AB - Insight can be defined not only in terms of people's understanding of their illness, but also in terms of understanding how the illness affects individuals' interactions with the world. The term 'insight' encompasses a complex concept which should not be considered as an isolated symptom which is present or absent. Instead, it may be more appropriate to think of insight as a continuum of thinking and feeling, affected by numerous internal and external variables. Different psychiatric disorders involve different mechanisms in the process of impairment of insight; this may influence the ways in which insight should be assessed in clinical practice. PMID- 1617370 TI - Evolutionary genetic theory. PMID- 1617371 TI - Western psychotherapy and non-Western populations. PMID- 1617372 TI - Western psychotherapy and non-Western populations. PMID- 1617373 TI - Suicide prevention. PMID- 1617374 TI - Suicide prevention. PMID- 1617375 TI - Neuroleptic malignant syndrome. PMID- 1617376 TI - The naming of syndromes [corrected]. PMID- 1617377 TI - The naming of syndromes. PMID- 1617378 TI - The naming of syndromes. PMID- 1617379 TI - Are non Western beliefs false? PMID- 1617380 TI - Idiopathic genital pain and fluvoxamine. PMID- 1617381 TI - 'The current literature'--Worcester Development Project. PMID- 1617382 TI - British Society for Rheumatology. IXth annual general meeting and VIIth Eulav Symposium in conjunction with the British Society for Rheumatology and the British League Against Rheumatism. 21-24 July 1992, London. Abstracts. PMID- 1617383 TI - Asthma. PMID- 1617384 TI - Asthma. Definition and clinical spectrum. AB - When variability and periodicity of symptoms and of airway function are accompanied by evidence of an allergic pathogenesis (identified inhalant precipitants, atopy, raised IgE, eosinophilia) the diagnosis of asthma is obvious to patient and physician. But many patients with asthma do not conform to this classic stereotype, so that considerable problems of distinction from other types of airway obstruction exist. These difficulties have practical significance because conferring the label of asthma is associated with physicians prescribing more intensive and effective treatment. PMID- 1617385 TI - Asthma. Epidemiology. AB - Ambiguities over the definition of asthma make both estimates of the prevalence of asthma and comparisons between studies difficult to interpret. Comparisons made within a study are, for this reason more informative. In children both asthma and wheeze appear to be commoner in boys with convergence of the rates during adolescence. There is regional variation in rates within countries and this is particularly marked in developing countries with low prevalence of disease in poor rural communities. Urban areas have a higher prevalence and racial differences have been noted in some studies. In the United States blacks have higher rates of both wheeze and asthma, but the differences are less clear cut in New Zealand and the United Kingdom. A lack of any association with social class has been reported from Australia, the United States, New Zealand, England and Wales, though some earlier studies have suggested an association with higher social class and Dawson et al. suggested that more severe disease was more common in poorer children. PMID- 1617386 TI - Asthma. Tracheobronchial vasculature. AB - The tracheobronchial vasculature consists of a subepithelial capillary network and a deeper system of blood sinuses or capacitance vessels. There seem to be no arteriovenous anastomoses. Sympathetic nerves constrict the vasculature by the transmitters noradrenaline and neuropeptide-Y, parasympathetic nerves dilate it by acetylcholine and vasoactive intestinal polypeptide, and sensory nerves release neuropeptides including substance P that are dilator. Most inflammatory mediators are also vasodilator. In asthma there is mucosal vasodilation due to the direct action of mediators on vascular smooth muscle, neuropeptides released by axon reflexes in sensory nerve receptors, and possibly reflex vasodilation due to stimulation of sensory nerves. The vasodilation increases the thickness of the mucosa, both by vascular engorgement and by increased interstitial liquid volume. This mucosal thickening will narrow the airways and increase the rigidity of their walls. The vascular bed is also dilated by cold and hyperosmolality, and this change may be a component of the bronchoconstriction due to hyperventilation, inhalation of cold air and exercise. Changes in mucosal blood flow influence the uptake of chemical agents from the lumen, and the success of aerosol therapy in asthma may to some extent depend upon the influence of mucosal blood flow. PMID- 1617387 TI - Plasma exudation and oedema in asthma. AB - Gross pathology, histological and ultrastructural observations and analysis of sputum and lavage fluid indicate that plasma exudation from the bronchial microvasculature and the formation of tissue oedema are characteristic features of asthma. Appropriate mediators for the induction of plasma exudation are generated in the blood and airways of asthmatic patients and when administered experimentally will cause plasma leakage and oedema. Plasma exudate may not only contribute directly to the thickened bronchial walls and mucus plugs in the airways of asthmatics, but may also play a role in epithelial shedding, thickening of the basement membrane, hypertrophy of the smooth muscle, inducing mucus secretion and in thickening the secreted mucus. The beneficial effect of corticosteroids in asthma may be due to an anti-leakage action. Development of drugs with a broad spectrum of action against mediator release may have therapeutic advantage over specific receptor antagonist drugs. PMID- 1617388 TI - Role of inflammatory mediators in asthma. AB - Release of inflammatory mediators such as histamine and products of arachidonic acid metabolism has been demonstrated in bronchoalveolar lavage fluid of patients with asthma. Their precise cellular source is not clear but many cells types such as eosinophils, macrophages and mast cells may contribute to the generation of a wide variety of chemical mediators. These can mimic many of the features associated with asthma including bronchoconstriction, bronchial hyperresponsiveness and airway microvascular leakage. Development of specific mediator receptor antagonists or inhibitors of mediator synthesis may clarify the role of particular inflammatory mediators such as the sulphidopeptide leukotrienes or platelet-activating factor in asthma. It seems unlikely that only one particular mediator is responsible for all the manifestations of asthma. PMID- 1617389 TI - Precipitating factors of asthma. AB - Asthma is characterised by bronchial hyperresponsiveness. This feature of the asthmatic diathesis predisposes patients to wheezing in response to a number of different factors. These precipitating factors include specific allergen acting via sensitised mediator cells through an IgE-dependent mechanism. There are irritants which may work through a non-specific manner, or stimuli such as exercise and hyperventilation, which probably also act through mediator release via a non-IgE-dependent manner. The mechanism whereby physical stimuli such as exercise induce bronchoconstriction is of interest, because it increases the context in which the mast cell may participate in acute asthmatic bronchoconstriction. Respiratory infections also commonly provoke asthma, especially in infants and may, indeed, precipitate the asthmatic state itself. Finally, drugs can often trigger asthma attacks and the mechanisms of asthma precipitated by non-steroidal anti-inflammatory drugs such as aspirin have been the subject of recent research. PMID- 1617390 TI - Asthma as an inflammatory disease: clinical perspectives. AB - Asthma is characterised by a persistent, ongoing airway submucosal inflammatory process which may underlie bronchial hyperresponsiveness and airways obstruction. Indirect assessment of airway inflammation includes examination of sputum or serum for eosinophils or eosinophil-derived products, but examination of bronchial mucosal biopsies or bronchoalveolar lavage fluid or cells remains the gold standard. Lymphocyte and eosinophil activation, with the release of certain cytokines such as interleukin-5, lipid mediators such as leukotrienes and eosinophil products such as major basic protein, may be important mechanisms of inflammation in asthma. Less invasive indirect measures of submucosal inflammation are needed to assess the impact of asthma treatment in the clinic. Antiinflammatory treatment in asthma should be introduced as early as possible. A greater understanding of the inflammatory mechanism or of the actions of corticosteroids may lead to the development of more effective and safer drugs for asthma. PMID- 1617391 TI - New developments in occupational asthma. AB - Recent developments in occupational asthma are reviewed. There are now three independent estimates of the incidence of occupational asthma in the general working population, which all identify the same high risk occupational groups (particularly those exposed to isocyanates and flour or wheat). The incidence of occupational asthma principally depends on the agent and level of exposure. The property of a small molecular weight chemical to bind to and alter the structure of body proteins seems important. Smoking both increases the number of workers developing specific IgE to occupational agents, and the number developing occupational asthma. The relation between increased non-specific bronchial responsiveness and occupational asthma is reviewed. Occupational sensitisation may be the cause of hyperresponsiveness, or develop in those with pre-existing hyperresponsiveness. Around 20% of workers with occupational asthma have measurements within the normal range. Once occupational asthma develops, removal from exposure, particularly if delayed, often results in continuing asthma. Finally the prevention of occupational asthma is discussed. PMID- 1617392 TI - Pathology of asthma. AB - Asthma is a clinically complex condition but at present the pathologist recognises only one disease process. The airways in fatal asthma are occluded by tenacious plugs of exudate, mucus and cells. There is fragility of the airway surface epithelium and thickening of epithelial reticular basement membrane. Bronchial vessel dilation, congestion and oedema, an intense inflammatory cell infiltrate and enlargement of the mass of bronchial smooth muscle, and mucus secreting gland each contribute to thickening of the airway wall. These changes contribute to the cardinal signs of inflammation (i.e. redness, heat, pain, swelling and secretion of mucus) and can profoundly modify the effects of airway contracture on airflow. The fragility and loss of surface epithelium, thickening of its underlying reticular layer and the presence of an inflammatory infiltrate, comprising activated T lymphocytes together with 'activated' and secreting eosinophils, are early events seen in biopsies of subjects with mild stable atopic asthma. PMID- 1617393 TI - Asthma. The mast cell. AB - The mast cell's association with asthma has a long history dating back to the turn of the century, when Dale and Laidlaw described histamine as a spasmogen for guinea-pig airways and a proposed mediator of acute anaphylaxis. Almost half a century elapsed before histamine was localised to the granules of mast cells, although the release of this and other mediators of the acute allergic reaction were known to involve reagin subsequently identified as IgE. The biochemical mechanisms involved in transduction signalling not only results in the calcium and energy-dependent release of preformed mediators by degranulation but also the generation and subsequent release of an array of newly formed products, many of which are derived from phospholipid precursors. PMID- 1617394 TI - Asthma. Eosinophils and neutrophils. AB - Eosinophils are strongly implicated as a major proinflammatory cell in the pathogenesis of asthma. Basic proteins from the crystalloid granule may be responsible for damage to mucosal epithelium whereas membrane-derived lipid mediators (particularly platelet activating factor and leukotriene C4) might directly influence bronchial smooth muscle contraction, microvascular permeability and mucus hypersecretion. The numbers of eosinophils and their products correlated with the severity of disease whereas successful treatment is usually associated with a resolution of local eosinophilia. Neutrophils may also be implicated in the pathogenesis of asthma but the evidence that this cell per se plays an important role remains controversial. Neutrophil products have the potential for altering airway function. More research is required to define the precise role of this cell type in asthma. It needs to be emphasised that the inflammation associated with bronchial asthma is complex and involves several cell types (i.e. T lymphocytes, mast cells and macrophages) in addition to the eosinophil and neutrophil. PMID- 1617395 TI - Asthma. Macrophages. AB - The airway macrophage has the characteristics required of the conducting cell in asthma. First, the airway macrophage is the most numerous cell within the airway lumen. Second, it can be activated by antigen and virus infections to release both spasmogens and chemotactic cytokines. Thus the common triggers to asthma are capable of activating the airway macrophage. Third, the response of the airway macrophage to therapeutic agents used in asthma bears a close similarity to the profile of disease modification with drugs in asthma, that is, they are inhibited by glucocorticosteroids but not beta 2-adrenoceptor agonists. PMID- 1617396 TI - Asthma. Epithelial cells. AB - The airway epithelium is the first line of defence against air-borne dusts, vapour, gases and fumes and plays a vital role in the maintenance of physico chemical homoeostasis. Perturbation of the epithelial cells which predominate within this barrier, may bring about adverse changes in and around the surrounding tissues playing a part in the pathogenesis of asthma. Although the specific mechanism(s) which partake in pathogenesis are not clear, several have been proposed. These include: (1) increased synthesis and release of inflammatory mediators and decreased synthesis of protective mediators; (2) synthesis of inflammatory cytokines; (3) modulation of cell adhesion molecules, important in determination of epithelial architecture; and (4) immunoregulation of the inflammatory cell types. It is likely that these operate together and interact to produce, initially functional changes in the epithelium, which lead eventually to the structural changes that are characteristic of the airway epithelium of asthmatics. PMID- 1617397 TI - The myxosporea of fish: a review. PMID- 1617398 TI - Serological response of chickens naturally infected with Salmonella typhimurium detected by ELISA. AB - Four laying flocks of chickens in Britain, each with a history of Salmonella typhimurium infection, were investigated serologically and bacteriologically. Blood samples were taken from identified birds from a single house on each site and sent to the Central Veterinary Laboratory, Weybridge for serological examination using enzyme-linked immunosorbent assays (ELISA) and rapid slide agglutination test (RST) using stained S. pullorum. The identified birds were taken to the local Veterinary Investigation Centre for bacteriological examination. On site A no salmonellae were recovered from birds in the house chosen for serological examination. Of these birds approximately 20% had antibodies to S. typhimurium in ELISA which used either a lipopolysaccharide (LPS) or heat-extract (HE) antigen from S. typhimurium. S. typhimurium was recovered from birds in one other of the four houses on the same site; these birds were not tested serologically. On site B, S. typhimurium was isolated from 8% of the birds examined. Of the total tested serologically, a third to half were seropositive by S. typhimurium ELISA using the LPS and HE antigen respectively. A small proportion of birds was seropositive by S. enteritidis ELISA and RST. No salmonellae were isolated from the other two sites although about 10% of birds tested on site C were seropositive in S. typhimurium ELISA. Cross-reactions were seen between S. typhimurium antigens in the ELISA and experimentally prepared antiserum to S. enteritidis. The S. enteritidis ELISA was generally more specific although cross-reacting antibodies were detected in sera from birds on sites A and B. PMID- 1617399 TI - The effects of fascioliasis on the activities of some drug-metabolizing enzymes in desert sheep liver. AB - Desert sheep experimentally or naturally infected with Fasciola gigantica were used to study the influence of infection on the activities of some drug metabolizing enzymes found in the liver. The enzymes investigated were aminopyrine N-demethylase, aniline 4-hydroxylase and UDP-glucuronyltransferase. The experimental infection was confirmed histologically by detection of Fasciola eggs in faeces and by measuring the activities of sorbitol dehydrogenase (SD), glutamate dehydrogenase (GD) and aspartate aminotransferase (AST) in plasma during the course of the disease. Liver specimens from naturally infected sheep were obtained from the slaughter house. The activities of aminopyrine N demethylase and aniline 4-hydroxylase were significantly decreased in sheep either naturally infected or during the acute stage of experimental fascioliasis (killed 5 weeks post-infection). The activity of UDP-glucuronyltransferase was decreased in naturally infected sheep and those killed 9 or 13 weeks post experimental infection. PMID- 1617400 TI - Serum protein values in canine diabetes mellitus, hypothyroidism and hypoadrenocorticism. PMID- 1617401 TI - Adaptability of the oxidative capacity of motoneurons. AB - Previous studies have demonstrated that a chronic change in neuronal activation can produce a change in soma oxidative capacity, suggesting that: (i) these 2 variables are directly related in neurons and (ii) ion pumping is an important energy requiring activity of a neuron. Most of these studies, however, have focused on reduced activation levels of sensory systems. In the present study the effect of a chronic increase or decrease in motoneuronal activity on motoneuron oxidative capacity and soma size was studied. In addition, the effect of chronic axotomy was studied as an indicator of whether cytoplasmic volume may also be related to the oxidative capacity of motoneurons. A quantitative histochemical assay for succinate dehydrogenase activity was used as a measure of motoneuron oxidative capacity in experimental models in which chronic electromyography has been used to verify neuronal activity levels. Spinal transection reduced, and spinal isolation virtually eliminated lumbar motoneuron electrical activity. Functional overload of the plantaris by removal of its major synergists was used to chronically increase neural activity of the plantaris motor pool. No change in oxidative capacity or soma size resulted from either a chronic increase or decrease in neuronal activity level. These data indicate that the chronic modulation of ionic transport and neurotransmitter turnover associated with action potentials do not induce compensatory metabolic responses in the metabolic capacity of the soma of lumbar motoneurons. Soma oxidative capacity was reduced in the axotomized motoneurons, suggesting that a combination of axoplasmic transport, intracellular biosynthesis and perhaps neurotransmitter turnover represent the major energy demands on a motoneuron. While soma oxidative capacity may be closely related to neural activity in some neural systems, e.g. visual and auditory, lumbar motoneurons appear to be much less sensitive to modulations in chronic activity levels. PMID- 1617402 TI - Factors in amphetamine-induced contralateral rotation in the unilateral 6-OHDA lesion rat model during the first-week postoperative: implications for neuropathology and neural grafting. AB - Amphetamine induced ipsilateral rotation in rats with chronic unilateral 6 hydroxydopamine (6-OHDA) lesions is a widely accepted line of evidence supportive of dopaminergic mediation of amphetamine effects on motoric behavior. However, there is literature indicating that amphetamine induces contralateral rotation, in the early postoperative phase of a unilateral 6-OHDA lesion. In an attempt to reconcile these opposite amphetamine effects on rotation in terms of dopaminergic mechanisms, a series of 4 experiments were conducted. These studies showed that amphetamine reliably elicits contralateral rotation for up to 7 days postoperative but only ipsilateral rotation thereafter. The amphetamine induced contralateral rotation differed behaviorally in several respects from subsequent ipsilateral rotation induced by amphetamine. It was comparatively more intense; and, while onset of peak rotation was dose dependent, rate of rotation was independent of dose level (0.5, 1.0 and 2.5 mg/kg). Dopamine and dopamine metabolite analyses by HPLC-EC after 3 postoperative intervals (days 3, 6, and 9) indicated a progressive and severe depletion of striatal dopamine in conjunction with elevated dopamine turnover. Importantly, after 6 days postoperative, dopamine was reduced to less than 0.06% after intact hemisphere but yet, amphetamine (1.0 mg/kg) elicited contralateral rotation. It was proposed that amphetamine could release a small amount of dopamine present in a sparse number of residual degenerating terminals and this dopamine, unrestricted by reuptake, could widely access supersensitive dopamine receptors to elicit contralateral rotation. This possibility calls into question amphetamine tests for neural graft efficacy in animal models which use amphetamine induced contralateral rotation as the criterion response. PMID- 1617403 TI - The role of laminin, a component of Schwann cell basal lamina, in rat sciatic nerve regeneration within antiserum-treated nerve grafts. AB - Regeneration of the sciatic nerve in transplanted nerve grafts in which laminin was inactivated was examined electron microscopically. Nerve grafts for transplantation were obtained from close cloned donor Wistar rats; 1-cm nerve segments of the sciatic nerve were frozen and thawed to kill the Schwann cells. Control recipient rats received grafts treated with normal rabbit serum to repair the artificially-made complete defect of the right sciatic nerve, and the experimental group of rats received grafts doubly treated with normal serum and rabbit anti-laminin antiserum. In the control grafts regenerating axons grew almost completely through the inside of the basal lamina scaffolds (92%) and adhered to the structure, while in the anti-laminin antiserum treated grafts the axons were present outside (52%) and inside (48%) the scaffolds simultaneously. In this case, the adhesion of axons to the scaffolds was obscure. Axons were associated with and without Schwann cells both inside and outside the basal lamina scaffolds. No unassociated Schwann cells were observed. The maximal number of axons in a 2 mm portion of the antiserum-treated grafts was approximately 250 axons per 100 x 100 microns square and 520 in the control at 15 days. At 30 days, almost the same number of axons was found at the distal (8 mm) portion of both groups. The growth in the former was delayed for 3 days. These results indicate that regenerating peripheral nerve axons may enter the basal lamina scaffolds and grow well because of the neurotrophic function of laminin present at the inner side of Schwann cell basal lamina. PMID- 1617404 TI - Time course of nigrostriatal system changes after tract hemisection and effects of ganglioside treatment: a multiple retrograde fluorescent tracing study. AB - The postlesion phenomena of nigrostriatal neurons following partial tract hemisection have been studied with retrograde axonal transport of dyes in rats treated with saline or GM1 ganglioside (30 mg/kg, i.p., daily for varying times). The time course of the plastic changes in both experimental animal groups was determined by a double retrograde fluorescent tracing technique, utilizing Fast blue (FB) as prelesion tracer, and Diamidino yellow (DY) as postlesion tracer. The data show that the number of nigral cells retrogradely labeled by the prelesion intrastriatal injection of FB declined progressively to 50% of their initial number over 3 weeks. The ganglioside treatment did not significantly influence this temporal pattern of labeled cell loss. By DY-labeling, an almost complete block of the retrograde axonal transport was observed up to 1 week postlesion and only after 3 weeks a partial recovery was evident, positively influenced by the GM1 treatment. Therefore, together with the findings on nigrostriatal cell loss, these data indicate that ganglioside treatment favors and/or accelerates the recovery of axonal transport of surviving nigral neurons but does not significantly affect their degenerative rate in the first 3 weeks after the lesion. PMID- 1617405 TI - Regional glucose metabolic changes after learning a complex visuospatial/motor task: a positron emission tomographic study. AB - Regional cerebral glucose metabolic rate (GMR) quantified with positron emission tomography (PET) with 18-fluoro-2-deoxyglucose (FDG) was measured twice in 8 young men performing a complex visuospatial/motor task (the computer game Tetris), before and after practice. After 4-8 weeks of daily practice on Tetris, GMR in cortical surface regions decreased despite a more than 7-fold increase in performance. Subjects who improved their Tetris performance the most after practice showed the largest glucose metabolic decreases after practice in several areas. These results suggest that learning may result in decreased use of extraneous or inefficient brain areas. Changes in regional subcortical glucose metabolic rate with practice may reflect changes in cognitive strategy that are a part of the learning process. PMID- 1617406 TI - The role of GTP binding proteins in ischemic brain damage: autoradiographic and histopathological study. AB - Cerebral ischemia produces perturbation of signal transduction systems in neurons. In order to estimate the contribution of guanine nucleotide-binding protein (G-protein) to hippocampal neuronal death, the effect of pertussis toxin (PTX) on the CA1 pyramidal cell damage after transient forebrain ischemia in rats was examined. PTX was administered 3 days before 20 min of transient forebrain ischemia. PTX injection into the CA1 subfield failed to alter the number of ischemic-damaged CA1 pyramidal cells. In contrast, ventricular PTX injection exacerbated CA1 pyramidal cell damage. We also studied postischemic alteration of GTP binding sites in the hippocampal formation using quantitative in vitro autoradiography. Autoradiographic imaging demonstrated predominant distribution of GTP binding sites in synaptic areas in the hippocampus. No significant change of GTP binding activity was observed in the hippocampus until 2 days after recirculation. Seven days after ischemia, when the CA1 pyramidal cells were depleted, the GTP binding sites of the strata oriens and radiatum in the CA1 subfield had reduced by 32% and 31%, respectively. In contrast, GTP binding in the CA3 subfield and the dentate gyrus remained unaltered throughout the reperfusion period. These results suggest that the amount of G-proteins as estimated by GTP binding remained unaltered in the hippocampus during the early recirculation period, when the CA1 pyramidal cells were morphologically intact, and that signal transduction pathways mediated by Gi and Go do not play a major role in delayed death of the CA1 pyramidal cells. PMID- 1617407 TI - Indole-N-methylated beta-carbolinium ions as potential brain-bioactivated neurotoxins. AB - N-Methyl-4-phenylpyridinium ion (MPP+), a highly toxic metabolite produced in the brain from a street drug contaminant, is selectively taken up by nigrostriatal dopaminergic neurons and accumulated intraneuronally in mitochondria. There it inhibits respiration, causes neuronal death and, in primates, provokes a parkinsonian condition. It has been suggested that endogenously generated or activated agents resembling MPP+ may contribute to the development of Parkinson's disease. We report here that simple beta-carbolines derived from tryptophan or related open chain indoles, when specifically methyl-substituted on both (2[beta] and 9[indole]) available nitrogens, display mitochondrial inhibitory potencies and neurotoxic effects in vitro (PC12 cultures) and in vivo (striatal microdialysis) which approach or even surpass MPP+. These results take on physiological significance with our finding that brain enzyme activity catalyzes S-adenosylmethionine-dependent methylations of the beta- and indole-nitrogens in beta-carbolines that have been detected in vivo. The unusual 9[indole]-N-methyl transfer, previously unrecognized in animals, apparently requires prior methylation of the 2[beta]-nitrogen. Sequential di-N-methylation of endogenous or xenobiotic beta-carbolines to form unique, neurotoxic 2,9-N,N'-dimethyl-beta carbolinium ions may serve as a brain bioactivation route in chronic neurodegenerative conditions such as Parkinson's disease. PMID- 1617408 TI - The occurrence of three isoenzymes of protein kinase C (alpha, beta and gamma) in retinas of different species. AB - The localisation and immunochemical identification of 3 different forms of protein kinase C (PKC-alpha, PKC-beta and PKC-gamma) in retinas of different species were analysed by immunohistochemistry and SDS-PAGE-Western blotting, respectively. Only in some cases was there a correlation between the findings from each procedure. One reason for the lack of correlation could be the small amounts of PKC present in some retinas, which made detection possible only by first concentrating the antigen by SDS-PAGE and then carrying out Western blotting. Another possible reason is that an antibody recognises unknown antigens immunohistochemically, but, because of their specific characteristics, they are denatured when subjected to SDS-PAGE and Western blotting and therefore remain undetected. PKC-beta immunoreactivity is present in rabbit, frog and goldfish retinas but absent from the rat retina. However, SDS-PAGE and Western blotting experiments showed that the PKC-beta isoenzyme is absent from the fish retina but present in the rat retina. PKC-beta immunoreactivity in rabbit retina is present in ganglion and/or amacrine cells; in the frog retina the enzyme is associated with some bipolar cells. In the goldfish retina, PKC-beta is associated with a large population of cells in the ganglion cell layer as well as with some amacrine cell bodies. PKC-alpha is present primarily in bipolar cells of rat, fish and rabbit retinas and was not detected by immunohistochemistry or blotting experiments in the frog retina. SDS-PAGE and Western blotting of retinal extracts from different species showed that PKC-gamma occurs in the rabbit where it was associated with ganglion and/or amacrine cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617409 TI - Monoamine-mediated enhancement of acetylcholine release in rat hippocampus by 6R L-erythro-5,6,7,8-tetrahydrobiopterin. AB - Recently, we reported that intracerebroventricular administration of 6R-L-erythro tetrahydrobiopterin (6R-BH4), a common natural cofactor for phenylalanine, tyrosine and tryptophan hydroxylases, enhances in vivo exocytotic release of acetylcholine (ACh) from the rat hippocampus, as monitored by brain microdialysis. In the present study, we developed a method for separation of ACh from 6R-BH4 on small columns of Sephadex G-10, which allowed us to determine by high pressure liquid chromatography (HPLC) the changes of ACh levels recovered in dialysates following addition of 6R-BH4 to the dialyzing fluid. Infusions of 6R BH4 (final concentration, 0.25, 0.5 and 1 mM in the perfusing fluid) produced concentration-dependent increases in ACh levels in dialysates (1.5-, 3- and 8 fold of the basal levels, respectively), but was without effect on choline levels in dialysates. Infusion of 6S-L-erythro-5,6,7,8-tetrahydrobiopterin (6S-BH4), an unnatural diastereoisomer of 6R-BH4, or L-erythro-biopterin (biopterin), an oxidized form of 6R-BH4, did not affect the ACh levels in dialysates. The 6R-BH4 induced increase in ACh levels persisted after pretreatment with atropine, a muscarinic antagonist, but did not occur in rats pretreated with reserpine to deplete monoamines. These results show that 6R-BH4 stimulates exocytotic ACh release in the hippocampus through action on a local monoaminergic system in the hippocampus. PMID- 1617410 TI - Actions of endothelin at the subfornical organ. AB - Endothelin (ET), a potent vasoconstrictor peptide, is believed to have central sites of action and potential neurohormonal effects relating to body fluid homeostasis and blood-pressure regulation. Systemic endothelin binds to receptors at circumventricular organs and has been shown to increase plasma concentrations of vasopressin and increase the firing frequency of neurohypophysial vasopressin and oxytocin neurons. In the present study we have examined the effects of ET on blood-pressure following micro-injection into the subfornical organ (SFO). Micro injection of 0.5 and 5.0 pmol of endothelin into SFO caused significant increases (10.1 +/- 1.1 and 10.2 +/- 2.1, respectively) in blood pressure, while lower doses were without effect. In addition, we have used single unit recording techniques to evaluate the effects of systemic ET on the activity of SFO neurons. Extracellular recordings from SFO neurons, antidromically identified as projecting to PVN, showed predominantly excitatory responses to systemic ET (21/35 cells). The data demonstrate that ET has excitatory actions on SFO neurons, and further raise the possibility that one of the functional consequences of such effects is an increase in arterial blood pressure. PMID- 1617411 TI - Medial septal modulation of entorhinal single unit activity in anesthetized and freely moving rats. AB - Reversible inactivation of the medial septal area results in a spatial memory impairment and selective disruption of hilar/CA3, but not CA1, location-specific discharge. The present study examined the possibility that such septal deafferentation produces effects on hippocampal function by altering physiological properties of the primary input and output structures for hippocampus, the entorhinal cortex and the subiculum, respectively. Single unit activity of hippocampal, entorhinal, and subicular cells was recorded before, during, and after septal injection of lidocaine in anesthetized rats. When compared to hippocampal cells, relatively few subicular and entorhinal cells showed a change in mean firing rate following septal inactivation. Entorhinal unit responses to septal inactivation (via tetracaine injection) were also examined in freely moving rats performing a spatial maze task. About one-third of entorhinal cells showed enhanced or reduced firing rates of 40% or more. Also, the spatial distribution of cells found in the superficial, but not deep, entorhinal layers became less clear following septal inactivation. Together, these data are consistent with the hypothesis that manipulation of the medial septum affects hippocampal function via its septosubicular and septo-entorhinal projections in addition to the more direct septohippocampal pathway. Since entorhinal cortical function was affected by tetracaine injection into the septum, it does not appear that direct entorhinal-CA1 afferents were primarily responsible for the maintenance of CA1 location-specific neural activity in previous septal inactivation experiments. Rather, these data are consistent with the hypothesis that the persistence of CA1 place fields was accomplished by intrahippocampal neural network operations. PMID- 1617412 TI - Pure Schwann cell suspension grafts promote regeneration of the lesioned septo hippocampal cholinergic pathway. AB - Regeneration of central nervous system (CNS) axons has been studied in the cholinergic septo-hippocampal system using various 'bridges' able to support fiber growth. In this study, a pure Schwann cell (Sc) suspension labeled with bisbenzimide (Hoechst 33342) was grafted in the lesioned septo-hippocampal pathway. At 2 weeks post-grafting, acetyl-cholinesterase (AChE)-positive fibers invaded the graft and grew in association with the Hoechst-labeled Sc, some of which expressed the low-affinity nerve growth factor receptor (NGF-R). At 2 months and 4 months post-grafting, the dorsal hippocampus was reinnervated with an apparently normal innervation pattern. Analysis of fiber growth in the hippocampus at four months post-grafting revealed a significant increase of reinnervation in the grafted animals (2 mm) compared to the non-grafted ones. No difference was observed in the number of cholinergic septal neurons expressing the NGF-R. These results demonstrate that a Sc suspension grafted into the lesioned septo-hippocampal system, integrates well into the host tissue, and supports axonal CNS outgrowth, implying that Sc by themselves provide an adequate environment for regeneration to occur. PMID- 1617413 TI - GFAP expression of human Schwann cells in tissue culture. AB - We have studied the expression of the intermediate filament (IF) proteins, vimentin and glial fibrillary acidic protein (GFAP), in cultured human Schwann cells (SC) from patients with different neuropathies and normal control cases. SC cultures from sural nerve biopsies of 8 subjects with axonal neuropathies, 8 with demyelinating neuropathies and 3 normal controls were included in this study and processed with double immunofluorescence technique, using anti-vimentin and anti GFAP antibodies, during the 2nd, 4th and 6th week of culture. Five cultures incubated with anti-GFAP antibodies were also processed for immunoelectron microscopy. Specificity tests of the used antibodies were performed. We have found that: (1) cultured human SC constantly express vimentin; (2) SC from normal controls are GFAP-negative in the first period of culture; (3) SC from pathologic nerves can contain GFAP-immunoreactive IF and the percentage of GFAP-positive SC is higher in axonal than in demyelinating neuropathies; (4) during the permanence in culture human SC from both normal and pathologic cases acquire the ability to synthesize GFAP. The obtained data suggest that the removal from axonal contact and the resulting loss of myelinating function induce a cytoskeletal cellular response in human SC characterized by the cytoplasmic accumulation of GFAP immunoreactive IF. PMID- 1617414 TI - Mechanism of delayed intracranial hypertension after cerebroventricular infusions in conscious rats. AB - Prior studies showed that cerebroventricular infusions of artificial cerebrospinal fluid, 8 microliter/min for 10 min, followed by a 10 min rest and a 24 h infusion of 0.5 microliters/min, raised cerebrospinal fluid pressure (CSFp) of conscious, unrestrained rats after about 2 h. Here, we report that the 10 min infusion alone evoked a delayed, prolonged rise in CSFp. Pressure during the infusion itself rose and recovered quickly, as is usually reported. Pressure/volume tests, used to calculate resistance to outflow (Ro) and compliance (C), revealed that infusions increased Ro and decreased C, after a delay (P less than 0.05). The rise in CSFp after infusion was blocked by pretreatment with acetazolamide + ouabain (P less than 0.05), but the delayed changes in Ro and C were unaffected. We suggest that the 10 min infusion of a sterile, balanced salt solution has a primary effect that increases Ro; as CSF synthesis continues, C is exhausted and the delayed rise in CSFp ensues. This non traumatic method of raising CSFp may be a useful method to study intracranial fluid dynamics. PMID- 1617415 TI - Characterization of the norepinephrine uptake system and the role of norepinephrine in the expression of the adrenergic phenotype by quail neural crest cells in clonal culture. AB - This study investigates the role norepinephrine (NE) may play in regulating the differentiation of quail neural crest cells into sympatho-adrenal cells. Cues originating from the embryonic microenvironment are thought to play an important role during development. It is conceivable that NE has a positive regulatory function because adrenergic expression by quail neural crest cells in clonal culture can be inhibited by NE uptake inhibitors such as desipramine (DMI). This possibility is further supported by the notion that in the avian embryo presumptive adrenergic neural crest cells are likely to encounter catecholamines shortly after they have acquired the NE uptake mechanism. Our present data indicate that neural crest cells in clonal culture express a high affinity NE uptake system that can be inhibited by desipramine. As in the embryo, it appears before noticeable levels of catecholamines are accumulated by neural crest cells, as judged by formaldehyde-induced catecholamine fluorescence (FIF). A comparison of the time course of appearance of different adrenergic markers suggests that immunoreactivity against the biosynthetic enzyme tyrosine hydroxylase (TH) may appear first, and that it is followed very closely by the appearance of detectable levels of dopamine-beta-hydroxylase (DBH) and the NE uptake mechanism. Accumulation of catecholamines (FIF) is observed last. Addition of exogenous NE leads to an increase in adrenergic expression in vitro as judged by an increase in the number of colonies containing FIF-positive cells as well as cells expressing the biosynthetic enzymes TH and DBH. This suggests that exogenous NE can play a positive regulatory role in the differentiation of quail neural crest cells into sympathoadrenal cells. PMID- 1617416 TI - Cellular correlates of classical conditioning in identified light responsive pedal neurons of Hermissenda crassicornis. AB - Cellular correlates of classical conditioning were examined in two recently identified light responsive pedal neurons. The correlates of conditioning consisted of significant decreases in the pedal cells' responses to light (conditioned stimulus) recorded from conditioned animals compared to random controls. Pedal cell P7, which exhibits an inhibitory response to light in naive animals, showed significantly less inhibition during a 5 min light step in conditioned animals as compared to random controls. Pedal neuron P9, which exhibits an excitatory response to light in naive animals, showed significantly less excitation during a 10 s light step in conditioned animals as compared to random controls. The changes in the response to light recorded from pedal neurons P7 and P9 in conditioned animals were not accompanied by any significant changes in membrane potential, action potential amplitude or dark-adapted spike frequency. PMID- 1617417 TI - Aberrant regeneration of motor axons into the pia mater after ventral root neuroma formation. AB - The spinal pia mater receives a rich innervation of small sensory and autonomic axons via the ventral roots. In the present study this pathway was interrupted by the transection of the L7 ventral root in young kittens. The animals were killed 12-18 months postoperatively. It was observed that the pia mater adjacent to the divided ventral root contained large numbers of myelinated axons. We suggest that these axons represent sprouts which had reached the pia mater by retrograde growth from the neuroma on the ventral root. Some of these aberrant pial axons ended blindly in the pia mater. Abnormal terminal-like swellings were observed along pial blood vessels. Fibers with diameters exceeding 11 microns were observed. Many fibers had an internodal spacing below 100 microns and the maximum value was only about 300 microns. Thus, motor axons which are forced to grow into a foreign territory show a maldevelopment which is more obvious with regard to nodal spacing than to fiber diameter. PMID- 1617418 TI - Electrically evoked turning: asymmetric and symmetric collision between anteromedial cortex and striatum. AB - Electrical stimulation of the anteromedial cortex (AMC) or striatum of rats evoked contraversive eye, head and body movements. In these experiments we test which neurons and which pathways are responsible for the turning by delivering conditioning (C) pulses to one site and test (T) pulses to the second site, and measuring the frequency of pulse pairs required to evoke a full turn in 10 s. Decreases in the required frequency were usually found at C-T intervals from 0.6 to 1.0 ms, whether the C pulses were delivered to the AMC or to the striatum. This symmetric effect is attributed to collision in fast-conducting axons connecting cortex and striatum. Symmetric collision at C-T intervals of 2-4 ms was observed between cortex and 3 dorsal striatal sites, suggesting slower axons from cortex to these dorsal striatal sites. In several animals, asymmetric changes in required frequency also occurred. When the C pulses were presented via the striatal electrode, the recovery in required frequency occurred at C-T intervals of 1-4 ms, but when the C pulses were presented via the cortical electrode, recovery occurred at C-T intervals of 2-50 ms. This asymmetry is attributed to indirect (i.e., transynaptic) activation of corticostriatal or striatal output axons. These results suggest that in both cortex and striatum there are synapses, transmitting from rostral to caudal, which are important for electrically evoked turning. When C and T pulses were delivered to the same site, decreases in required frequency occurred at C-T intervals from 0.4 to 4 ms, attributable to recovery from refractoriness. In 3 striatal sites, however, large changes were also seen at C-T intervals from 6 to 50 ms. In all 3 sites, asymmetric collision occurred at these same intervals. The recovery at long C-T intervals could be due to transynaptic collision also, resulting from the simultaneous activation of presynaptic and postsynaptic axons by a single striatal electrode. PMID- 1617419 TI - DSP-4, a noradrenergic neurotoxin, produces more severe biochemical and functional deficits in aged than young rats. AB - The present study examines the effects of noradrenergic lesions (either DSP-4 i.p. or 6-hydroxydopamine (6-OHDA) into the dorsal noradrenergic bundle on biochemical (noradrenaline (NA), dopamine (DA), serotonin (5-HT) and choline acetyltransferase (ChAT) activity) and cortical EEG (quantitative EEG (qEEG) and high-voltage spindle (HVS)) activity in young and aged rats. Near complete 6-OHDA NA lesions, but not partial DSP-4 NA lesions, increased HVS activity in young rats. DSP-4 and 6-OHDA lesions produced no significant changes in the 5-HT or DA levels or in the ChAT activity in young rats. In some of the aged rats, DSP-4 produced similar biochemical and HVS effects, as it induced in young rats. In the remainder of the aged rats, NA levels were greatly and 5-HT levels slightly decreased. DA levels and ChAT activity were unaltered in either set of aged rats. HVS activity was increased only in that group of aged rats with the greatly lowered NA content. These results suggest that: (1) some of the aged rats are more sensitive to DSP-4 treatment than young adult rats; and (2) NA depletions have to be complete to produce an increase in HVS activity in young and aged rats. PMID- 1617420 TI - Passive electrical properties of motoneurons in aged cats following axotomy. AB - The objective of this study was to determine whether the aging process influences the changes in the electrophysiological properties of motoneurons that occur as a consequence of axotomy. Accordingly, using intracellular recording and stimulating techniques, the basic electrical properties of control (unaxotomized) and axotomized spinal cord motoneurons of aged cats were determined. Compared with control motoneurons, axotomized motoneurons exhibited increases in input resistance (Rin), membrane time constant (tau b) and the equalizing time constant (tau c). While the electrotonic length (L) remained unchanged, axotomy induced a decrease in the total cell capacitance (Ccell). The post-axotomy reduction of Ccell indicates that the motoneuron surface area was reduced and the increased membrane time constant indicates that there was an increase in membrane resistivity (Rm). The post-axotomy conservation of L accompanied by an increase in Rm suggests that aged axotomized motoneurons undergo geometrical changes. Furthermore, calculations based on cable theory suggest that the diameter of the equivalent cylinder (d) decreased following axotomy, whereas the equivalent cylinder length (l) remained unaffected. It is concluded that axotomy produces significant alterations in the soma-dendritic portion of aged spinal motoneurons, as indicated by the changes found in their passive electrophysiological properties, and that the pattern of the response that occurs in axotomized motoneurons of adult cats is also present in axotomized motoneurons of aged animals. PMID- 1617421 TI - Electrical states in the rabbit brain can be altered by light and electromagnetic fields. AB - The effect of low-frequency magnetic fields on the rabbit electroencephalograph (EEG) was studied using a quantitative procedure that permitted statistical evaluation of the response of individual animals. The field conditions used were those predicted by various theories to result in field-animal interactions; light and sham exposure were employed as positive and negative controls, respectively. Sixty-seven percent of the rabbits exhibited changes in the EEG power spectra when light was presented in 2-s epochs; none of the animals responded to sham exposure. When 1 Gauss, 5 Hz, was presented in 2-s epochs, 100% of the animals tested responded to the presence of the field. The rabbits did not respond when the magnetic-field frequency was higher than the physiological range (1-20 Hz) or when it was tuned for resonance of K+. The results showed that an electrical state function may be operationally defined for the rabbit brain, and used to assess the occurrence of an interaction between an animal and external magnetic fields. PMID- 1617422 TI - Activation of nerve growth factor synthesis in primary glial cells by phorbol 12 myristate 13-acetate: role of protein kinase C. AB - Phorbol 12-myristate 13-acetate (PMA) induces a dramatic production of nerve growth factor (NGF) in primary cultures of newborn mouse astrocytes maintained in a serum-free medium. This stimulation is dose-dependent and a maximal effect on the levels of cell-secreted factor was observed at a concentration of 10 nM. At this concentration, the promoting effect of PMA appears much more important than that elicited by 10% fetal calf serum (FCS) under the same culture conditions. PMA acts primarily on the accumulation of NGF mRNA, which was detected by northern blot analysis after 6 h of treatment. This accumulation may be totally or partially prevented when PMA-treated glial cells are concomitantly exposed to the protein kinase inhibitors H-7, H-9, and to a lesser degree, HA-1004. The known specificity of these inhibitors agrees with the possibility that protein kinase C (PKC), which constitutes so far the sole known target of PMA, represents a key element involved in the stimulation of NGF gene. The role of PKC is further supported by the observation that alpha phorbol didecanoate, which has no activity on PKC, is depleted of effect on the synthesis of NGF. Likewise, 1,2 dioctanoylglycerol (1,2-DOG) has a weak, but significant promoting action on the production of NGF, unlike the 1,3-isomer which is not active on PKC. Finally, a treatment of 15 min with 100 nM PMA is sufficient to stimulate the cells, suggesting that the activation phase of PKC, rather than its down regulation, constitutes an important trigger leading to an increased expression of the NGF gene.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617423 TI - Intracellular HRP study of nociceptive neurons within the ventrobasal complex of the cat thalamus. AB - Locations and morphological characteristics of nociceptive specific (NS) and wide dynamic range (WDR) neurons of the ventrobasal (VB) thalamic complex were studied using an intracellular HRP injection technique in cats anesthetized with urethane and chloralose. Both NS and WDR neurons were found within the marginal zone of the VB complex. Their somata were confined to the VB complex, but dendrites were extended into the structures of the thalamus surrounding the VB complex. NS neurons were found in the caudal part of the VB complex, whereas WDR neurons were found more rostrally. Examinations of their locations within the marginal zone of the VB complex confirmed the somatotopic organization, as found previously. We also confirmed the previous reports that there are 3 different types of low threshold mechanoreceptive (LTM) neurons within the VB complex. They are type I, type II and type III neurons. Both NS and WDR neurons were either type I or type II neurons. Obvious morphological differences were not found between LTM neurons and two classes of nociceptive VB neurons investigated. PMID- 1617424 TI - Chronic lithium administration alters a prominent PKC substrate in rat hippocampus. AB - The therapeutic effect of lithium in the treatment of bipolar disorder exhibits a significant delay in the onset of action and a persistence of efficacy beyond abrupt discontinuation of treatment. Lithium is known to alter receptor-coupled phosphoinositide second messenger pathway in brain, resulting in indirect changes in an endogenous activator of protein kinase C (PKC). Such evidence has suggested that PKC may be involved in the mechanism of action of lithium in the brain. PKC represents a site wherein long-term regulatory changes in cell function occur through the phosphorylation of specific phosphoproteins involved in processes including neurotransmitter release and receptor activation. In studies of rats exposed to lithium, however, we have found no significant effects of chronic administration on the relative activity, subcellular distribution, or activation of PKC in hippocampus. We did find a major reduction in the in vitro PKC mediated phosphorylation of two major substrates, 83 kDa and 45 kDa, in hippocampus of rats exposed to chronic lithium and maintaining clinically relevant therapeutic levels in brain. Using immunoblot analysis we have identified a known myristoylated alanine-rich C kinase substrate (MARCKS) at 83 kDa. In vivo levels of MARCKS in hippocampus were found to be significantly reduced after chronic lithium exposure. These findings persist in animals withdrawn from lithium, but are not apparent following acute treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617425 TI - Characterization of prolactin receptor in human brain and choroid plexus. AB - We have studied the binding of 125I-labeled human prolactin (PRL) to membranes from various regions of the human brain (hypothalamus, cerebral cortex, cerebellum and choroid plexus) derived from autopsy specimens. Among the various regions studied, the choroid plexus of both male and female subjects showed the highest specific binding and a clearly detectable specific binding was also observed in the hypothalamus of both sexes, whereas it was very low in other brain regions. No significant sex differences in PRL binding to various brain regions were observed except for the hypothalamus where a higher binding was seen in female subjects. The binding did not vary with the age of the subjects. Moreover, the cause of death and the time elapsed from death to autopsy in this study did not affect the binding significantly. The binding of 125I-labeled human PRL to hypothalamus and choroid plexus membranes from female specimens was inhibited in a dose-dependent manner by both unlabeled human and ovine PRL and by human growth hormone (GH), but not by other polypeptide hormones. Scatchard analysis of the binding revealed the presence of saturable binding sites with low capacity and high affinity for human PRL ligand. These results provide strong preliminary evidence for the presence of PRL binding sites in the human brain. PMID- 1617426 TI - Adenosine inhibition of the regeneration in vitro of adult frog sciatic sensory axons. AB - The sensory axons of the adult frog sciatic nerve have earlier been shown to regenerate in vitro. If a local test crush is made at the initiation of culturing, regeneration starts after 3.4 days and proceeds at a rate of about 0.8 0.9 mm/day for several days. In the present experiments regeneration was inhibited by adenosine in a reversible and dose-dependent fashion. Similarly, both an adenosine analogue, 2-chloroadenosine (2-CA), and a non-hydrolyzable ATP analogue, AMP-PNP, reduced the outgrowth of sensory axons. The effect of adenosine was partially antagonized by theophylline at a critical concentration. Using a compartmental system, it could clearly be shown that adenosine exerted its effects at the outgrowth region. Adenosine, 2-CA, and AMP-PNP were also found to inhibit the proliferation of Schwann cells in the regenerating nerve. Various experiments showed that the latter can not explain the outgrowth inhibitory effects, which could be mediated by adenosine receptors associated with the elongating axons. PMID- 1617427 TI - Decreased [3H]hemicholinium binding to high-affinity choline uptake sites in aged rat brain. AB - The binding of [3H]hemicholinium ([3H]HCh-3) to sodium-dependent high-affinity choline uptake sites provides a useful neuroanatomical and functional marker of the cholinergic system. We examined the autoradiographic distribution of [3H]HCh 3 binding sites in the forebrain of young (4-6 months) and old (32 months) rats. There was a widespread reduction of [3H]HCh-3 binding site density in the aged rat brain. This loss presented regional differences with maximal reduction in the medial and posterior striatum (55%) and in the dentate gyrus (47%), in limbic areas such as basolateral amygdala, tubercle olfactorium and piriform cortex the autoradiographic signal was about 25-30% lower. In aged hippocampus and cerebral cortex the density of [3H]HCh-3 binding sites was about 40% lower, the difference between young and senescent animals being less evident in the medial septum and basal nucleus. No significant alterations were observed in interpeduncular nucleus from old rats. These data are in agreement with the functional results obtained by measuring other cholinergic parameters in the aged rat and confirm the vulnerability of cholinergic system during aging. PMID- 1617428 TI - Norepinephrine activates potassium conductance in neurons of the turtle cerebral cortex. AB - Whole-cell voltage and current clamp recordings were obtained from cortical neurons of the pond turtle, Pseudemys scripta elegans. Norepinephrine (NE) induced an outward current in 50% of pyramidal neurons. This current had a reversal potential of -88.3 +/- 3.2 mV, consistent with a K+ conductance increase, and had a mean amplitude of 18.3 +/- 7.2 pA at -40 mV. The ionic dependence and pharmacological analyses are both consistent with alpha 2 adrenergic receptor stimulation. Inhibition of Na(+)-dependent action potentials with TTX did not diminish the NE-induced K+ conductance, indicating that NE acts directly on the postsynaptic neuron. In addition to effects on postsynaptic conductance, NE dramatically decreased the amplitude of spontaneous inhibitory postsynaptic currents (IPSCs) in 55% of pyramidal neurons. The decrease in spontaneous IPSCs was observed both in those neurons which exhibited an increase in K+ conductance in response to NE administration (81%) and in those which did not (33%). Thus, NE modulates neuronal excitability both directly by activating a postsynaptic K+ conductance and indirectly by decreasing spontaneous IPSCs. PMID- 1617429 TI - Learning impairment following intracerebral administration of the HIV envelope protein gp120 or a VIP antagonist. AB - The external envelope glycoprotein (gp120) of the human immunodeficiency virus (HIV) has been shown to be toxic to neurons in culture. To further investigate the neurological effects of gp120, the involvement of this protein with the acquisition of spatial discrimination was assessed. Both native and recombinant gp120 were administered into the cerebral ventricles of adult rats and performance was evaluated in the Morris swim maze. Gp120 treatment retarded acquisition after daily administration of 12 ng. The specificity of this impairment was demonstrated in that the performance of animals given the same amount of gp160 from recombinant baculovirus was not different from animals given saline. Vasoactive intestinal peptide (VIP) has been shown to block gp120-induced neurotoxicity in culture and a VIP receptor antagonist has displayed toxic properties to neurons in culture. We show here that this antagonist, which competitively inhibits VIP binding and blocks VIP-mediated functions in cell cultures from the CNS, also produced an impairment of performance. This retardation was attenuated by cotreatment with VIP, supporting the specificity of the observed impairment. Thus, gp120 and the VIP antagonist produced similar retardation of spatial discrimination, suggesting that both may impair memory for spatially related stimulus control. PMID- 1617430 TI - Effects of nerve growth factor on TTX- and capsaicin-sensitivity in adult rat sensory neurons. AB - We have investigated the effects of nerve growth factor (NGF, 2.5 ng/ml for 1-2 weeks) on enriched adult rat dorsal root ganglion (DRG) neurons maintained in cell culture in defined media. Whole-cell recordings in cells cultured in the absence and presence of NGF revealed no significant difference in resting membrane potential and input resistance. However, the threshold for spike generation was significantly lower in untreated cells than in treated cells; -25 +/- 1.1 mV vs -19 +/- 2.2 mV, respectively. The sensitivity of the Na+ spike to tetrodotoxin (TTX, 1 microM) was different in cells cultured in the absence or presence of NGF. For example, spikes were abolished by TTX in 100% of untreated cells, while in NGF-treated cells the spike was abolished in only 41% of the neurons. Chemosensitivity of DRG neurons was also different in the absence and presence of NGF. For example, the percent of neurons in which a current activated by 8-methyl-N-vanillyl-6-nonenamide (capsaicin, 500 nM) was detected, increased from 18% in untreated cells to 55% in NGF-treated cells. NGF did not influence the number of cells surviving. The results indicate that NGF can regulate TTX and capsaicin sensitivity in these adult rat sensory neurons. Our experimental protocol indicates that this effect is not mediated by a factor in the serum or released from non-neuronal cells. PMID- 1617431 TI - The interaction of testosterone with the brain of the orchidectomized primate fetus. AB - At certain times during gestation, the testes of the fetal macaque produce plasma levels of testosterone (T) that are similar to those of adults. It is thought that testosterone acts on the brain via estrogen and androgen receptors to organize the development of sexually dimorphic neural structures that underlie sex differences in behavior. To test the proposition that there are male-female differences in the occupation of steroid receptor binding sites during fetal development in the cynomolgus macaque, we have compared the uptake of [3H]T and its metabolites in: (1) 5 intact males (plasma T 571.2 +/- 215.5 ng/100 ml); (2) 5 intact females (33.8 +/- 25.2 ng/100 ml); (3) in 5 males orchidectomized in utero (14.6 +/- 5.7 ng/100 ml). About 1 week after fetal gonadectomy or sham operation, all fetuses were given 500 microCi [3H]T s.c. and were then delivered 60 min later by Cesarean section. Brains were removed and dissected into blocks containing the hypothalamus and preoptic area, amygdala, hippocampus, and midbrain. Samples of cerebral and cerebellar cortex were also obtained. Purified nuclear pellets were prepared by centrifugation through 2 M sucrose and were extracted into ether and analyzed by high performance liquid chromatography. Hypothalamic nuclear concentrations of [3H]E2 in intact males (847 +/- 195 dpm per mg DNA) were significantly lower than those in sham-operated females (2147 +/ 542 dpm per mg DNA) (P less than 0.05), but those in orchidectomized males (2233 +/- 345 dpm per mg DNA) were similar to concentrations in females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617432 TI - Current source density of sustained potential shifts associated with electrographic seizures and with spreading depression in rat hippocampus. AB - The membrane currents responsible for the sustained potential shifts associated with electrographic seizures and with spreading depression in hippocampus were studied in the anesthetized rat. Probes incorporating 16 sensors in a straight line, spaced at 150-microns distances, were recording the potential changes with DC-coupled amplifiers in CA1 and dentate gyrus (DG) of one hemisphere. Seizures and spreading depression were provoked by repetitive stimulation of different afferent pathways. Seizures always began in DG before CA1, regardless of the pathway stimulated. Tonic seizures were associated with a sustained negative potential shift that was largest in the cell body layers. Current source density was computed from these recordings and confirmed the presence of a current sink limited to the cell body layer throughout the duration of electrographic seizures. Spreading depression was associated with a very large sink located in the layer of apical dendrites, maximal among the proximal segment of dendrites, to which the cell body layer served as a source. We conclude that seizures are associated with an inward current in neuron cell bodies, probably flowing through membrane channels of as yet no know physiological function. PMID- 1617433 TI - Projections from the nucleus accumbens to cholinergic neurons of the ventral pallidum: a correlated light and electron microscopic double-immunolabeling study in rat. AB - A correlated light- and electron microscopic double-immunolabeling study combining choline acetyltransferase immunocytochemistry with anterograde tracing of Phaseolus vulgaris leucoagglutinin (PHA-L) revealed that axons of the nucleus accumbens terminate on cholinergic neurons of the ventral pallidum. These findings are discussed with respect to the possibility that these cholinergic neurons may be part of parallel circuits, providing feedback to the same cortical and amygdaloid areas which innervate the nucleus accumbens. PMID- 1617434 TI - Modulation of lateral hypothalamic activity by olfactory bulb and sciatic stimulation. AB - Lateral hypothalamic area (LHA) single unit activity (extracellular) was studied in response to electrical stimulation of the olfactory bulb (OB) or sciatic nerve in adult albino rats (n = 39) anesthetized with dialurethane. Olfactory stimulation resulted in a greater proportion of LHA units showing inhibitory rather than excitatory responses, while sciatic nerve stimulation resulted in similar proportions of units showing inhibitory and excitatory responses. Of the 76 LHA units tested with both OB and sciatic nerve stimulation, 36% responded to both stimulation sites, 18% responded only to OB stimulation, 26% responded only to sciatic nerve stimulation, and 20% were unresponsive to either stimulation. The locations of responsive units were diffuse throughout the LHA sampled. The response characteristics of LHA neurons to external sensory stimulation are consistent with the anatomy and putative integrative functions of this brain region. PMID- 1617435 TI - Effect of drinking on angiotensin-II-induced shifts in regional cerebral blood flow in the rat. AB - A map of brain regions affected by central administration of the octapeptide angiotensin II (AII) and that would further reflect the consequences of AII's well-known dipsogenic action was developed. Regional cerebral blood flow (rCBF) as an indicator of neuronal activity was measured in conscious rats shortly after an ICV bolus injection of 100 ng AII or saline vehicle (VEH). AII-treated animals were further subdivided into two groups that were either permitted to drink [AII (W+)] or whose water was removed when drinking was attempted [AII (W-)]. When compared to VEH condition, blood flow increased significantly within 1 min after AII treatment in 33 of 53 regions sampled in those rats not given an opportunity to drink. In 11 of these 33 regions, ingestion of a small amount of water was associated with a reversal of AII-induced elevation in blood flow [i.e., AII (W+) less than AII (W-)]; these regions included the organum vasculosum lamina terminalis, rostral lateral hypothalamus, supraoptic nuclei, rostral zona incerta, and median eminence. A group of similarly treated rats exhibited a significant elevation of mean arterial blood pressure following AII treatment without significant shifts in arterial blood gases, pH, or bicarbonate. These data are consistent with prominent involvement of the anteroventral third ventricular region of the rat brain. The results further indicate that rCBF may be a sensitive measure for the identification of central sites of action of AII as a dipsogenic agent and may reveal distinctions between regions associated primarily with initiation of drinking and those reflecting the results of subsequent behavioral events. PMID- 1617436 TI - Validation of the hypothermic action of preoptic norepinephrine in guinea pigs. AB - Conscious guinea pigs were either microinjected intrapreoptically (iPO) with various doses of norepinephrine (NE) bilaterally or microdialyzed with pyrogen free saline (PFS) or 10 micrograms/microliters NE unilaterally immediately and unilaterally or bilaterally 2 days after probe insertion. Core temperature (Tco), skin temperature (Tsk), and rate of oxygen consumption (VO2) were monitored continuously. The microinjection of low doses of NE induced Tco rises, whereas that of the highest dose (10 micrograms/microliters) caused an initial Tco fall followed by a rise. The microdialysis of PFS or NE immediately after probe insertion caused Tco rises; the former was abolished and the latter was converted into a fall by indomethacin (Indo, a prostaglandin synthase inhibitor) pretreatment. Two days later, PFS evoked no thermal response whereas NE induced a Tco fall; neither response was affected by Indo pretreatment. The falls in Tco produced by NE microdialyzed uni- or bilaterally were similar. The microdialysis of NE induced a 15% reduction in metabolic rate but no change in Tsk. These results indicate that the Tco rise induced by NE microinjected iPO is a methodological artifact mediated by PGE2, whereas the Tco fall observed in its microdialysis appears to represent the authentic physiological action of this transmitter effected by a reduction in metabolic rate. PMID- 1617437 TI - Development of gamma-aminobutyric acid-immunoreactive neurons in normal and intracranially transplanted retinas in rats. AB - Retinas from embryonic day 14 Sprague-Dawley rats were transplanted intracranially to the midbrain or cortex of newborn (P0) rats with right eyes enucleated at the time of transplantation and the gamma-aminobutyric acid (GABA) immunoreactivity in developing retinal transplants, host as well as normal retinas, was studied. The results showed that GABA-immunoreactive neurons were identified in retinas of normal and host rats from the day of birth (P0) onward and that their somata were distributed primarily in the inner half of the internal nuclear layer and in the ganglion cell layer. The adult pattern of GABA immunoreactivity was first observed at P16 when several immunoreactive sublaminae were clearly identifiable in the inner plexiform layer. In contrast, gamma aminobutyric acid-immunoreactive somata could not be identified in retinal transplants until P4, with a significant reduction in the density and number of GABAergic neurons detected by P12. Moreover, only two immunoreactive sublaminae were observed in the inner plexiform layer in all transplants at P12, as well as in more mature stages. These results suggest that significant changes occurred in the GABA system of the transplanted retina, despite the fact that the overall pattern of organization of the GABAergic neurons and their processes in the retinal transplants was comparable to that of the normal retina. PMID- 1617438 TI - Release of angiotensin in response to ionic stimulation: a possible role for calmodulin in the secretory event. AB - Although the synthesis and distribution of the putative neurotransmitter angiotensin (ANG) has been well established, little is known about the mechanism for its release. In this study, we utilized dissociated cell cultures of fetal rat brain to examine the cellular and ionic properties of angiotensin release. Graded concentrations of 0-60 mM KCl in the presence of 5 mM CaCl2 were added to the cultured cells and the resulting angiotensin release was measured by radioimmunoassay and high-performance liquid chromatography. Levels of angiotensin release increased from 13.85 +/- 1.53 pg/mg protein to 172.64 +/- 17.49 pg/mg protein with increasing concentrations of K+. Cultures incubated with 60 mM KCl buffer that did not contain CaCl2 released 39.87 +/- 15.74 pg ANG/mg protein. To further show the link between ionic stimulation and angiotensin release and determine the potential role of extracellular sodium ions on angiotensin release, cultures were incubated with the Na(+)-channel blocker tetrodotoxin (300 nM TTX) prior to maximal stimulation with 60 mM KCl/5 mM CaCl2 in the presence of the channel antagonist. Release was attenuated following incubation with stimulating buffer containing TTX (300 nM) to 5.49 +/- 4.37 pg/mg protein. Finally, to determine the role of the calcium binding protein calmodulin in the release event, the cells were incubated with graded concentrations of W-7 (2.5-250 microM) and subsequently stimulated with 60 mM KCl/5 mM CaCl2 in the presence of the calmodulin antagonist. W-7, which displays specificity for inhibition of the Ca2+/calmodulin complex below 0.2 mM, decreased angiotensin release in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617439 TI - Influence of nucleus tractus solitarius stimulation and baroreceptor activation on rat parabrachial neurons. AB - The parabrachial nucleus (PBN) within the dorsolateral pons is a major recipient of autonomic-related inputs from more caudal levels of the brainstem and, in particular, the nucleus of the solitary tract (NTS). Although the anatomical projections from the NTS to the PBN are well characterized, less is known concerning the influence of activating NTS efferents on PBN neurons and the response of the latter to cardiovascular-related inputs. The present study examined the response of PBN neurons to electrical stimulation of the depressor area within the NTS in urethane anesthetized rats, and subsequently, the influence of arterial baroreceptor activation and systemic angiotensin II (ANG II) on these cells. Extracellular single-unit PBN recordings indicated that 92 of 227 (40.5%) cells were orthodromically excited and 35 of 227 (15.4%) inhibited consequent to NTS stimulation. Ten (4.5%) PBN cells displayed antidromic activation from the NTS. Of 41 of 119 neurons responding to both NTS stimulation and baroreceptor activation, 29.3% revealed a excitatory and 31.7% an inhibitory response to the two stimuli. Fifteen PBN cells responded to NTS stimulation, baroreceptor activation, and the administration of systemic ANG II, with six cells displaying either an excitatory or inhibitory response to all three stimuli. These observations provide electrophysiological support for reciprocal connections between the NTS and PBN and indicate the presence of both excitatory and inhibitory projections to the pontine nucleus. A population of neurons influenced by activation of NTS efferents also reveal a similarity of responses to inputs originating from peripheral arterial baroreceptors and systemic ANG II. PMID- 1617440 TI - Excitation of hypothalamic paraventricular neurons by stimulation of the raphe nuclei. AB - Extracellular recordings were made from 467 anti-dromically identified neurosecretory neurons and 148 non-neurosecretory neurons in the paraventricular nucleus of the hypothalamus of hemispherectomized cats under pentobarbital anesthesia. Stimulation of the dorsal, median, and pontine raphe nuclei excited 31%, 26%, and 12% of neurosecretory neurons tested, respectively, and inhibited 9%, 7%, and 8%. The excitatory responses in 13 of 14 neurons tested were blocked by either of two intravenously administered 5-HT2 antagonists, cyproheptadine or methysergide. The 5-HT1A antagonist, (-)pindolol, partially blocked the excitatory responses elicited by raphe stimulation in three of five neurons tested. The inhibitory responses to raphe stimulation were not affected by application of these antagonists. More non-neurosecretory neurons than neurosecretory neurons were excited in response to raphe stimulation and these excitatory responses were also blocked by these antagonists. We conclude that most electrically stimulated synaptic inputs from the midbrain raphe nuclei to the hypothalamic paraventricular nucleus are excitatory and are mainly mediated by 5-HT2 receptors. PMID- 1617441 TI - Chronic ethanol treatment reduces inhibition in CA1 of the rat hippocampus. AB - The effect of chronic ethanol exposure on inhibition in the rat hippocampal slice was investigated using paired-pulse stimulation techniques with stimulation in stratum radiatum or stratum oriens of CA1. Experimental animals were fed ethanol in a liquid diet for 20 weeks and were withdrawn for at least 8 weeks prior to electrophysiological recording. Prior ethanol treatment had no effect on basic input-output relationships for the extracellular population spike. Ethanol treatment significantly reduced the recurrent inhibition produced by antidromic stimulation in a manner dependent upon stimulus intensity. In addition, with orthodromic paired-pulse stimulation of either stratum radiatum or oriens, a trend toward an augmentation of the facilitation of population spike amplitude was observed, suggesting that feedforward inhibition may also be reduced. These results are similar to those found with treatments that reduce inhibition. Therefore, we conclude that chronic ethanol exposure produces an enduring disruption of inhibitory neuronal function in the rat hippocampus. PMID- 1617442 TI - NADPH-diaphorase activity in the hypothalamic magnocellular neurosecretory nuclei of the rat. AB - A histochemical study of the distribution of NADPH diaphorase activity in the hypothalamus of normal rats was carried out. Our study demonstrates the presence of NADPH-diaphorase activity in the circularis and anterior and posterior fornicals nuclei for the first time. Additionally, we confirm the presence of NADPH-diaphorase-stained neurons in the paraventricular (both magno- and parvicellular neurons) and supraoptic nuclei, as well as a population of isolated positive neurons (not included in any hypothalamic nuclei) located among the different nuclei. Because NADPH diaphorase has recently been shown to be a nitric oxide synthase, our study reveals a wide presence of this enzymatic activity in the hypothalamus of the rat. PMID- 1617443 TI - Rapid morphological changes in supraoptic nucleus and posterior pituitary induced by a single hypertonic saline injection. AB - Neurosecretory neurons of the supraoptic nucleus (SON) which manufacture, transport, and secrete neuropeptide hormones are activated by administration of hypertonic NaCl. Male rats were given single intraperitoneal injections of isotonic (0.15 M) or hypertonic (1.5 M) NaCl solution and sacrificed 5 h after injection. Electron micrographs were compared to determine morphological differences in the SON and in the neural lobe in the two conditions. In the SON, significant decreases were found in the extent of glial contact with the magnocellular neuroendocrine cell (MNC) membrane; the amount of nerve terminal contact and amount of apposition of MNC membrane with other MNC cell bodies or dendrites increased. The number of multiple synapses (one terminal contacting two or more cells) per 100 microns of somatic membrane in the 1.5 M NaCl condition was double that found in the 0.15 M NaCl condition. Size of nucleoli, overall cell body size, and amount of Golgi apparatus were significantly larger in the animals injected with 1.5 M NaCl. The neural lobes of animals receiving 1.5 M NaCl injections showed increased neural contact with the basal lamina and decreased cytoplasmic enclosure of axon terminals. The large and rapid changes induced by this stimulus suggest that it is an extremely effective activator of morphological plasticity in the hypothalamo-neurohypophysial system. PMID- 1617444 TI - Visualization of efferent retinal projections by immunohistochemical identification of cholera toxin subunit B. AB - The present study describes the use of cholera toxin subunit B as an anterograde and retrograde neuronal tracer for studying retinal projections of the rat, mouse, gerbil, and hamster. The tracer was pressure injected in the posterior chamber of the eye and the labeled neurons were identified using an avidin-biotin immunoperoxidase technique using diaminobenzidine as chromagen. Doses of 3-8 microliters (30-80 micrograms) cholera toxin subunit B and a survival for 24 h resulted in an optimal transport of the tracer in all rodent species investigated. The cholera toxin subunit B-containing retinal efferents were effectively stained and yielded the presence of axons with delicate boutons on passage and nerve endings. Smooth and thick fibers were also observed, indicating a distinction between passing and terminating axons, respectively. Immunoreactive axons were observed in the hypothalamus, thalamus, ad mesencephalon, and the precise distribution of positive nerves could be identified in counterstained sections, some of them as delicate endings in apposition to neuronal surfaces. Labeled cell bodies were observed in the oculomotor nucleus and the pretectum, indicating that the tracer is transported retrogradely as well. Because the tracer is identified immunohistochemically, the retinofugal and retinopetal pathways can be mapped more precisely, perhaps in combination with immunohistochemical detection of other antigens. PMID- 1617445 TI - Estrogen-like effects of the mammary carcinogen 7,12 dimethylbenz(alpha)anthracene on hypothalamic neuronal membranes. AB - Previous studies have shown that in Sprague-Dawley female rats, but not in Wistar females, the mammary carcinogen dimethylbenz(alpha)anthracene (DMBA) results in extended preovulatory prolactin and estradiol surges, associated with inhibition of preovulatory gonadotropin surges, and in the induction of mammary tumors. Because earlier studies of similar endocrine states have shown this to be linked to hypothalamic arcuate nucleus neuronal membrane organization, in this study freeze-fracture methodology was used to determine whether DMBA may affect the ultrastructure of the neuronal membrane in the arcuate nucleus. The effects of estradiol valerate and DMBA were studied on 55- to 60-day-old cycling females, in Sprague-Dawley and Wistar rats, 8 weeks after the treatment. DMBA alone (15 mg/rat by gastric intubation) resulted in a significant decrease in the numerical density of intramembrane protein particles (IMP) in Sprague-Dawley rats but not in Wistar rats. The SC injection of estradiol valerate (1 mg/rat) resulted in a significant decrease of IMP numbers in both strains of rats. Although the subcutaneous injection of DMBA alone (1 mg/rat) did not affect IMP numerical density in either strain, the same potentiated the effect of estradiol valerate (1 mg/rat) on IMP's in Sprague-Dawley but not in Wistar females. These results indicate that DMBA affects the organization of neuronal plasma membrane in the hypothalamus of Sprague-Dawley rats. Wistar females are insensitive to both the endocrine and neuronal membrane effects of DMBA. Estradiol affected neuronal membranes in both strains and potentiated DMBA's effect. It appears that the estrogen-sensitive mechanism of DMBA activation may be lacking in Wistar rats. PMID- 1617446 TI - Fluoxetine shortens circadian period for wheel running activity in mice. AB - Fluoxetine is a potent and specific serotonin re-uptake inhibitor and an effective antidepressant drug. Male mice were treated with either fluoxetine (8 mg/kg body weight per day) or saline. Wheel running activity was monitored for 2 weeks in a 12:12 LD cycle followed by 2 weeks in constant darkness (DD). Fluoxetine significantly shortened free-running circadian period for wheel running activity (23.93 +/- 0.08 h for fluoxetine treated mice versus 24.17 +/- 0.07 h for saline treated mice; p less than 0.03). These results are consistent with a role for serotonin in the regulation of circadian period in mice. PMID- 1617447 TI - Microinjection of the alpha 1-agonist methoxamine into the paraventricular hypothalamus induces anorexia in rats. AB - Adrenergic receptors within the paraventricular hypothalamus (PVN) play a prominent role in the control of food intake: stimulation of alpha 2 adrenoceptors induces food intake whereas stimulation of alpha 1-adrenoceptors suppresses food intake. This study further examines the role of PVN alpha 1 adrenoceptors by examining the effects on food and water intake of the alpha 1 adrenergic agonist methoxamine (100, 200, 400 nMol) microinjected into the rat paraventricular hypothalamus. Methoxamine suppressed food intake but not water intake. Doses of 100, 200, and 400 nMol methoxamine suppressed food intake by 47%, 64%, and 96%, respectively. These results further confirm the hypothesis that administration of alpha 1-agonists into the PVN acts to significantly suppress food intake; an action that is in opposition to the facilitory effects of alpha 2-adrenergic agonists on food intake. PMID- 1617448 TI - Administration of satiety factors and gustatory responsiveness in the nucleus tractus solitarius of the rat. AB - The administration of certain factors associated with postprandial satiety decreases gustatory responsiveness. We compared the effects of intravenous injections of glucose, insulin, pancreatic glucagon (PG), and cholecystokinin (CCK) on multiunit activity evoked from taste responsive neurons in the nucleus tractus solitarius of rats. Glucose, insulin, and PG reliably suppressed evoked responses to lingual application of 1.0M glucose, whereas responses that followed CCK remained unchanged. A common physiological consequence of glucose, insulin, and glucagon is increased glucose availability which may impact directly on gustatory neurons or indirectly through modifications in ventral forebrain or vagal afferent activity. PMID- 1617449 TI - Auditory magnetic source localization in twins. AB - We recorded magnetoencephalographic (MEG) auditory evoked fields (EF) from the L and R hemispheres of 12 paris of twins, 6 monozygotic (MZ), and 6 dizygotic (DZ) and localized the source of the 100 msec latency EF component termed the M100. M100 sources exhibited greater similarity in location in MZ twin pairs, especially in the L hemisphere. These findings support the hypothesis that the functional location of processing of nonmeaningful unattended auditory stimuli may depend more heavily on left hemisphere structures. Furthermore, genetic effects are evident in these left hemisphere structures and their activity, as is a substantial amount of environmental variance. PMID- 1617450 TI - Iron induces degeneration of nigrostriatal neurons. AB - Parkinson's-diseased (PD) brains have been reported to contain increased quantities of iron within the zona compacta of the substantia nigra (SN). To test whether excess iron in the SN could cause a PD-like loss of dopaminergic neurons, various concentrations of iron were infused unilaterally within the SN of adult male rats. At 1-2 months post-infusion, examination of thionine and iron stained brain sections from animals infused with low concentration iron revealed: (1) iron diffusion limited to and concentrated within the infused SN and (2) a selective degeneration of neurons within zona compacta of SN. Infusion of higher iron concentrations induced near complete neuronal losses in zona compacta, as well as neuronal degeneration within zona reticularis and areas immediately adjacent to the SN. Striatal dopamine and its catabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were reduced in a dose-dependent fashion, with over 80% depletions observed at the highest iron concentration infused. These data indicated that neurons within zona compacta of SN are sensitive to infusions of low iron concentrations. The data support the notion that iron in zona compacta of the SN could act as an endotoxin in the pathogenesis of PD. PMID- 1617451 TI - Degenerative changes in traumatic brain injury: post-injury magnetic resonance identified ventricular expansion compared to pre-injury levels. AB - Magnetic resonance (MR) scans obtained 42 days and 10 months post-injury were compared to scans obtained in similar planes three months prior to injury. In comparison to pre-injury scans, post-injury MR scan analysis demonstrated significant ventricular volume increase which is considered a measure of the degree of diffuse axonal injury. Most important, the trauma induced degenerative effects appeared to be quite complete by 42 days post-injury as there was little further degeneration that occurred between the 6 week and 10 month post-injury scans. This study demonstrates that in humans the majority of gross trauma induced degenerative changes are complete by 6 weeks post-trauma. PMID- 1617452 TI - Effect of paradoxical sleep deprivation on vasoactive intestinal peptide-like immunoreactivity in discrete brain areas and anterior pituitary of the rat. AB - To determine whether vasoactive intestinal peptide (VIP) is involved in paradoxical sleep (PS) homeostasis, VIP-like immunoreactivity (VIP-LI) of discrete brain areas was determined by radioimmunoassay after 24 and 48 h of PS deprivation by the watertank technique followed or not by 5 h of sleep rebound. This study was carried out with an environmental control (placed in dry watertank: DWC) and a nonstressed control. Such PS deprivation induced a decrease of VIP content in PS-deprived rats restricted to cortex and anterior pituitary. In the cortex, the decrease in VIP-LI was of the same magnitude after 24 and 48 h of PS deprivation and VIP-LI was normal by 5 h of sleep rebound; as such a decrease was also observed after 48 h in DWC, it could be due to the stress related to the experiment rather than lack of sleep. In the anterior pituitary, the decrease was related to the duration of deprivation with a greater decrease in VIP-LI after 48 than after 24 h of PS deprivation and specifically related to PS deprivation since it was not observed in DWC rats. After 5 h of sleep rebound, recovery of VIP-LI was total in the 24-h experiment and partial in the 48-h one. In all eight other structures studied, VIP was unchanged after experimentation. These results strongly suggest that VIP is not involved in PS homeostasis but as indicated by other experiments more probably in circadian organization of sleep. PMID- 1617453 TI - The locus coeruleus and dopaminergic function in rat brain: implications to parkinsonism. AB - Clinical and experimental evidence suggests that degeneration of the locus coeruleus (LC) may be responsible for certain symptoms of Parkinson's disease (PD). We have, therefore, studied the effects of LC lesion on dopamine (DA) metabolism in the rat striatum. Unilateral depletion of norepinephrine (NE) was obtained by stereotaxic injection of 6-hydroxydopamine (6-OHDA) into the dorsal NE bundle (DNEB). Rats were sacrificed 1 or 3 weeks after lesioning. 6-OHDA induced approximately 50% depletion of NE in the ipsilateral hippocampus at 1 week postinjection, and over 75% depletion after 3 weeks. DNEB lesions had no effect on DA or DOPAC levels in the ipsi- or contralateral striatum at either time point. Lesions also failed to affect DA synthesis or utilization in either striatum. The metabolism of exogenous levodopa in the striatum was also unaffected. It is suggested that any possible effect of the LC on DA transmission in the striatum is not mediated by the DNEB. PMID- 1617454 TI - Postnatal development of gustatory recipient zones within the nucleus of the solitary tract. AB - Previous studies have examined pre- and postsynaptic development of the first order central gustatory relay, located in the rostral nucleus of the solitary tract (NST). This region of the NST is innervated by primary gustatory axons arising from the facial-intermediate nerve. However, a large portion of the gustatory NST is innervated by axons arising from the glossopharyngeal nerve, and although the time course for development of N.VII recipient zones has been defined development of glossopharyngeal afferent terminal fields has not been examined. Moreover, the time course for development of projection neurons located postsynaptic to gustatory afferent axons has not been examined in any portion of the NST. The objectives of the present study were to 1) define the time course for development of N.VII and N.IX terminal fields and 2) examine temporal relationships between development of afferent terminal fields and development of projection neurons located postsynaptic to gustatory afferent axons. To this end, triple fluorescent labeling procedures were used to simultaneously visualize developing axons and projection neurons. Results show that afferent terminal fields develop along the rostrocaudal axis of the NST. Axons of the N.VII terminal field are present in the rostral NST at P1 and develop to approximately P25. Axons and terminal endings of N.IX do not enter the NST until approximately P9-P10, and these terminal fields develop within the intermediate NST until approximately P45. Many NST neurons destined to project axons to the second-order central gustatory relay, located in the caudal parabrachial nucleus (PBN), do not possess axonal connections with the PBN during the first 2-3 weeks of postnatal life. As afferent terminal fields develop, these neurons establish connections with the PBN between the ages of approximately P7 and P45-P60. The delay between afferent terminal field development and development of PBN projection neurons in the N.VII terminal field is approximately 3 weeks. The delay between pre- and postsynaptic development in the N.IX terminal field is approximately 1 week. Potential relationships between pre- and postsynaptic development are discussed, in addition to relationships between anatomical development in the NST and the emergence of taste-guided behaviors. PMID- 1617455 TI - Immunocytochemical survey of haloperidol-induced immunoreactive changes of [Met]enkephalin-Arg6-Gly7-Leu8 in the rat forebrain. AB - It has already been demonstrated that chronic treatment with the dopamine receptor blocker, haloperidol, results in an increase of proenkephalin-A-derived peptides in the caudate-putamen (CP). To examine this phenomenon at the cellular level, we used immunocytochemistry to investigate the effects of haloperidol on [Met]enkephalin-Arg6-Gly7-Leu8 (MEAGL) immunoreactivity in the rat forebrain. After daily haloperidol (5 mg/kg, IP, for 6 days) or haloperidol decanoate (70 mg/kg, IM, given once or twice) treatment, immunoreactive neurons appeared diffusely in the whole CP and in the core part of the nucleus accumbens (Acb) and less frequently in the outer shell part of the Acb and the cell-dense layer of the tuberculum olfactorium (TuO). Increase of MEAGL-immunoreactive fibers in the CP, Acb, and TuO was also detected after these treatments, a particularly prominent increase being found in the striopallidal terminals in the globus pallidus and ventral pallidum. Haloperidol or haloperidol decanoate had no effect on MEAGL immunoreactivity in the cerebral cortex, amygdala, or hypothalamus. Reserpine treatment (5 mg/kg, IP, for 6 days) caused similar effects on the dorsal and ventral striopallidal system, and the direct injection of 6 hydroxydopamine (10 micrograms/5 microliters) into the CP led to the appearance of MEAGL-immunoreactive neurons in accordance with the depleted dopaminergic terminal area. These findings suggest that haloperidol influences enkephalinergic neurons region specifically and that in the dorsal and ventral striopallidal enkephalinergic system haloperidol increases MEAGL immunoreactivity in cell bodies, fibers, and terminals by blocking intrastriatal dopaminergic neurotransmission. PMID- 1617456 TI - Electrophysiological properties of in vitro intrinsic cardiac neurons in the pig (Sus scrofa). AB - Physiological properties and synaptically mediated responses of 34 ganglionated plexus neurons from the right atrium of the pig heart were studied with in vitro intracellular recording techniques. Whole-cell input resistance of these neurons was lower, time constant was shorter, and threshold for directly evoked action potentials was higher than the same properties in extracardiac autonomic neurons. Long intracellular depolarizing current pulses (400-500 ms) failed to generate more than one or two action potentials. Nicotinic and non-nicotinic synapses were present on neurons in cardiac ganglia and neuronal properties could be modified by norepinephrine. Based on their physiological properties, cardiac ganglionated plexus neurons in the pig appear to represent a distinct population of autonomic neurons that may be capable of intracardiac integration of efferent information to the heart. PMID- 1617457 TI - Cerebral blood flow and metabolism in soman-induced convulsions. AB - Regional cerebral blood flow (CBF) and regional cerebral glucose utilization (CGU) were studied by quantitative autoradiographic techniques in rats. Animals were treated either with a toxic dose of soman, an irreversible organophosphorus cholinesterase inhibitor, that produced convulsions or with saline as controls. An increased arterial blood pressure (mean increase = 41% of control) always preceded onset of convulsions. Convulsive activity was associated with an increase of plasma glucose concentration and marked increases over controls of CGU [average of all regions: control = 75 +/- 5 mumol.100 g-1.min-1, n = regions/animals (304/8); seizures = 451 +/- 20 mumol.100 g-1.min-1, n = 190/5] and CBF [average of all regions: control = 135 +/- 6 ml.100 g-1.min-1, n = 190/5; seizures = 619 +/- 29 ml.100 g-1.min-1, n = 190/5). Regional distribution of these effects revealed a greater proportional increase of CBF over CGU in cingulate, motor, and occipital cortex and caudate-putamen. In contrast, a lower proportional increase of CBF over CGU in CA3 region of hippocampus, dentate gyrus, medial thalamus, and substantia nigra was observed, implying the existence of a relative ischemia in these brain areas. These findings may be relevant to the pathogenesis of brain lesions associated with soman-induced convulsions. PMID- 1617458 TI - Action of habenular efferents on ventral tegmental area neurons studied in vitro. AB - Action of habenular efferents on neurons of the ventral tegmental area (VTA) was studied with a slice preparation that preserved the habenula (Hb) and the VTA together with the interconnecting fiber bundle, the fasciculus retroflexus (FR). In the VTA, two types of neurons, presumably corresponding to the dopaminergic and nondopaminergic neurons, were discerned on the basis of the electrophysiological properties. Of 52 VTA neurons sampled, 42 [with the mean resting membrane potential of 56 +/- 7 mV (mean +/- SD)] responded with excitatory postsynaptic potentials (EPSPs) to FR stimulation. The EPSPs were monosynaptic in nature and rather weak in effect in the sense that they rarely triggered spikes. No significant differences in latency, duration, and time to peak were noted between the EPSPs generated in different types of neurons. FR stimulation evoked inhibitory postsynaptic potentials (IPSPs) in only six neurons, their resting membrane potential being 51 +/- 4 mV. The IPSPs frequently showed a fluctuation in latency. FR stimulation also produced antidromic responses in a few VTA neurons, but their long latencies precluded the possibility that the VTA-Hb projections contributed to the FR-evoked orthodromic responses in the VTA. EPSPs evoked by FR stimulation could be suppressed by kynurenic acid (1 mM). The findings indicate that the efferents of the Hb primarily have an excitatory effect on VTA neurons of any type and that the excitation may be mediated by amino acid receptors. PMID- 1617460 TI - Reevaluation of the plasticity in the rat supraoptic nucleus after chronic dehydration using immunogold for oxytocin and vasopressin at the ultrastructural level. AB - It has been shown that during physiological stimuli, such as dehydration, supraoptic nucleus (SON) neurons undergo profound morphological changes. However, little is known about how much each type of cell, oxytocin (OT) or vasopressin (VP), contributes to this plasticity during dehydration. Using postembedding immunogold cytochemistry for both OT and VP hormones at the electron microscopic level, we address this question. Rats were chronically dehydrated (given 2% saline to drink for 10 days) and their SON neurons were studied morphologically. The results were compared to control animals with free access to water. Both VP and OT somata showed an enlargement in size in dehydrated animals. Percentage of somasomatic/dendritic membrane contact increased significantly in both VP and OT neurons, with no significant changes in percentage of coverage of the cells by astrocytic membrane. Only the VP cells had a lesser amount of axosomatic membrane contact after dehydration, possibly due to an increase in cell size rather than a decrease in synaptic contact. Multiple synapses (MSs) (i.e., terminals that form more than one synapse with adjacent somata and or dendrites) occurred only between positively labeled cells and between negatively labeled cells, but not between positively and negatively labeled cells. The number of MSs per 100 microns OT somatic membrane or per 100 OT cells was significantly higher in dehydrated rats but was unchanged with regard to VP neurons. These findings indicate that both VP and OT neurons undergo morphological changes during chronic dehydration and, thus, that plasticity is not limited to OT cells as some earlier reports have suggested. PMID- 1617459 TI - Microelectrophoretic application of kainic acid into the globus pallidus: disturbances in feeding behavior. AB - Body weight changes, food and water intake, and sensorimotor disturbances of male rats were studied after bilateral kainic acid-(KA) induced lesions of the globus pallidus (GP). To minimize the extent of damages, KA was applied electrophoretically by means of glass micropipettes (tip diameter of the pipettes was 10-15 microns). The neuron-specific damages of the GP resulted in aphagia and adipsia and rapid body weight decrease. Lesioned animals showed permanent motor disturbances but only temporary difficulties in the orientation toward sensory stimuli. Our data show that the selective destruction of the GP neurons results in a complex disorder that has motivational, (sensori)motor, and metabolic components. PMID- 1617461 TI - Effects of thyrotropin-releasing hormone, oxytocin, and prolactin on thiopenthal induced narcosis in rats. AB - Neuropeptides that may induce behavioral activation--thyrotropin-releasing hormone (TRH), oxytocin (OXY), and prolactin (PRL)--were tested on thiopenthal induced narcosis after IV administration in male rats. TRH caused a significant shortening of sleeping time at the doses of 3 and 5 mg/kg, but did not change this parameter at lower doses. Oxytocin was effective at all doses tested (200, 300, and 400 micrograms/kg). Prolactin also shortened sleeping time at the doses of 0.2 and 1 mg/kg administered IV, slightly increasing it at the dose of 5 mg/kg. These results indicate that various neuropeptides are capable of reducing the duration of thiopenthal-induced sleep in rats. PMID- 1617463 TI - Spike-train analysis reveals "overshoot" in developing rat prefrontal cortex function. AB - A multivariate analysis of spontaneous single neuron firing in the developing prefrontal cortex (PFC) of urethane anesthetized rats has been made using selected spike-train parameters. In particular, the development of modal interspike intervals closely paralleled the volumetric 'overshoot' reported earlier by us for rat PFC. Thus, the growth phase is characterized by progressively higher firing rates associated with longer modal intervals (i.e., a change from phasic to tonic firing, suggestive of increasingly effective inhibition). In contrast, the subsequent abrupt reduction in PFC volume is accompanied by the appearance of extremely short interspike intervals with no concomitant change in overall mean discharge rates ('burst' firing). This last development could be largely due to the 'pruning' of excessive excitatory synaptic contacts. PMID- 1617462 TI - Species differences in amphibian olfactory neuron reactivity to a monoclonal antibody. AB - A monoclonal antibody immunostained a subpopulation of olfactory sensory neurons in cryostat sections of the olfactory mucosa of the grass frog, Rana pipiens, and the bullfrog, Rana catesbeiana. However, in the olfactory tissues of the African clawed frog, Xenopus laevis, only mucus and mucus-secreting components were stained, and no cell-specific immunoreactivity was seen in the tiger salamander, Ambystoma tigrinum. This antibody is a useful marker of olfactory neuronal subpopulations in some amphibians and illustrates the difficulties in cross species immunocytochemistry. PMID- 1617464 TI - The effects of low pass filtering on central somatosensory conduction time. AB - Central Somatosensory conduction time (CSCT) in the rat was measured by simultaneously recording the cortical somatosensory evoked potential (SEP) and cervical SEP and then subtracting the peak latency of the cervical response from that of the primary cortical response. The low frequency (high pass) filter of the recording system was kept fixed at 3.2 Hz but the high frequency cut-off was progressively raised from 32 to 16 kHz to examine the effects of low pass filtering on the two waveforms from which CSCT is derived. With a bandpass of 3.2 32 Hz, no activity could be reliably identified in either the cortical or cervical traces. With subsequent rises in the high frequency filter, the amplitude of both potentials increased with a concomitant decrease in their latencies. Stable values were obtained with a bandpass of 3.2-3.2 kHz and there was little additional change in waveform configuration. In contrast to the waveforms, low pass filtering had only minimal effects on CSCT and near constant values (in the range 3.6-4.1 ms) were obtained regardless of the setting of the low pass filter. I concluded that low pass filtering has a largely uniform effect on somatosensory activity generated in both primary cortical and cervico medullary locations. PMID- 1617465 TI - Immobility-reducing effects of antidepressants in a genetic animal model of depression. AB - Chronic treatment with the tricyclic antidepressants imipramine (15 mg/kg) and desmethylimipramine (5 mg/kg) significantly reduced the exaggerated immobility normally exhibited by the Flinders Sensitive Line (FSL) rats in the Forced Swim Test. The control group, Flinders Resistant Line (FRL) rats were only slightly affected. In contrast, chronic treatment with the anticholinesterase diisopropyl fluorophosphate at doses known to down regulate muscarinic receptors did not alter swim test immobility in either FSL or FRL rats. Our findings support the validity of the FSL rats as an animal model of depression and suggest that serotonergic and/or noradrenergic, but not cholinergic mechanisms, may underlie the exaggerated immobility of the FSL rats. PMID- 1617466 TI - Cocaine-induced suppression of renin secretion is mediated in the brain: investigation of cardiovascular and local anesthetic mechanisms. AB - Acute cocaine reduces renin secretion. To determine a peripheral versus central site of action, intracerebroventricular (ICV) versus intraperitoneal (IP) injections of cocaine were compared. Cocaine was more potent reducing plasma renin activity (PRA) and concentration (PRC) when injected ICV (0.050 mg/kg) than IP (5 mg/kg), suggesting a central site of action. Furthermore, addition of cocaine (10(-4) M) to kidney slices in vitro did not influence renin release, indicating that cocaine does not suppress renin secretion by acting directly in the kidney. We also investigated whether the hypertensive or local anesthetic properties of cocaine mediate its inhibition of renin secretion. Therefore, we compared the cardiovascular and endocrine effects of cocaine with those of the local anesthetic drug procaine. Both cocaine and procaine (500 micrograms/kg, ICV) produced rapid and short-term increases in blood pressure, but cocaine decreased PRC whereas procaine increased PRC. Intra-arterial (IA) and IP injections of cocaine also reduced PRC whereas procaine had no effect (IA) or elevated PRC (IP). Together, the data suggest that cocaine decreases renin secretion by acting in the brain. It is not likely that the cardiovascular or local anesthetic actions of cocaine are the main cause of its suppressive effect on renin secretion. PMID- 1617467 TI - Parenting stress and child maltreatment in drug-exposed children. AB - This study was conducted to examine the relationship between prenatal exposure to drugs and parenting stress and child maltreatment. The sample was comprised of 48 subjects including 24 drug-exposed children and a comparison group of 24 non-drug exposed children matched on age, race, gender and socioeconomic status. The subjects' age ranged from 1 to 33 months with a mean of 13 months. As predicted, mothers who used drugs during pregnancy reported higher levels of stress than foster mothers and comparison mothers on total parenting stress, child related stress, and parent related stress as measured by the Parenting Stress Index (Abidin, 1990). Biological mothers and foster mothers of drug-exposed infants scored higher than comparisons on child-related stress, most notably in the areas of hyperactivity, distractability and adaptability. A strong association was found between maternal use of drugs and child maltreatment serious enough to necessitate removal of the children by CPS. Over 40% of the drug-exposed children were in foster care, most often with maternal grandmothers. Most mothers who used drugs during pregnancy were polysubstance abusers and 21% were intravenous drug users increasing the risk of HIV infection for mothers and children. Implications for intervention are discussed. PMID- 1617468 TI - Children's strategies for coping with adverse home environments: an interpretation using attachment theory. AB - The coping strategies of four groups of maltreated children were compared with those of adequately reared children. The children were videotaped in a brief play session with their mothers, then in the Strange Situation, and finally during free play while the parent(s) were being interviewed. The coded videotapes of mother-child interaction yielded four scores for the children: cooperation, compulsive compliance, difficultness, and passivity. The coded videotapes of the Strange Situation yielded ten patterns of child attachment to the mother. The coded observations of play during the interview were analyzed in terms of seven child behaviors. The results indicated that abused, and abused-and-neglected children were difficult or compliant in interaction with their mothers, avoidant under stress, and aggressive with siblings; neglected children were cooperative in play with the mother, anxious under stress, and aggressive with siblings; adequately reared children were cooperative with both their mothers and siblings and secure under stress. Older children who had experienced abuse were less difficult and more compulsively compliant. Both marginally maltreated and adequately reared 1-year-olds were more difficult than either older or younger children from those groups but at all ages cooperation was the dominant pattern. The coherencies in the children's coping strategies were interpreted in terms of underlying internal representational models of relationships. PMID- 1617469 TI - Early identification of maternal depression as a strategy in the prevention of child abuse. AB - Maternal suicide and infanticide are merely the extreme tip of the iceberg of psychological and social morbidity associated with post-partum depression. Despite research indicating an association between maternal depression and disturbed parent-child interaction, maternal depression has been largely ignored in the literature on child maltreatment and in child protection practice. Practitioners should be alert to the potential risks to the child associated with maternal depression. In cases where child abuse has occurred, they should consider the possibility that the mother is depressed and that this needs to be treated as a problem in its own right. In terms of prevention of child maltreatment, early identification of maternal depression is an important strategy in which primary health workers have an important role. This study investigates the feasibility of broadening the traditional infant health focus of the role of the Australian Maternal and Child Health Nurse or Public Health Nurse to encompass maternal emotional and social well-being. Using quantitative and qualitative methods, the conditions under which mothers would find this acceptable, and the factors that facilitate or constrain such role redefinition are analyzed. PMID- 1617470 TI - Professional attitudes regarding the sexual abuse of children: comparing police, child welfare and community mental health. AB - A survey was completed involving three of the key professional groups engaged in the investigation and treatment of child sexual abuse. Police, child welfare and community mental health in a large, rural geographic area in Canada completed attitudinal items relating to professional response to child sexual abuse. An empirical scale was created which was comprised of three orthogonal factors, each with acceptable levels of internal consistency: 1) Beliefs in regard to the extensiveness and seriousness of the issue; 2) treatment versus punishment priority; and 3) view regarding identity of those who perpetrate child sexual abuse. Important gender differences were found across professional groupings in attitude toward sexual abuse. Greatest difference in attitude between service sectors was tied to emphasis placed on treatment versus punishment as a primary aspect of professional intervention. Significant differences were found between child welfare and police, the two service sectors most needing a coordinated approach during the "investigative phase" of professional intervention. PMID- 1617471 TI - The ability of elementary school children to learn child sexual abuse prevention concepts. AB - This research was designed to address several of the methodological problems in the current body of knowledge on the efficacy of child abuse prevention programs for elementary school-aged children. A new measure, the Children's Knowledge of Abuse Questionnaire (C.K.A.Q.) was developed, and its psychometric properties assessed. In total, 400 children were tested in four groups. Half of the sample participated in a child abuse prevention program Touching, and the other half were in a waiting list control group. Half of each group were pretested, and the other half were not, in order to determine whether the pretesting sensitized the students. All children were tested again 5 months afterward to investigate the long-term retention of prevention concepts. Results showed that children who participated in the prevention program scored significantly higher on the C.K.A.Q. than children in the control condition. Age was a critical factor, with significant improvements as age increased between the kindergarten, Grade 1, Grade 3 and Grade 6 students. All participants maintained their level of knowledge after 5 months had passed. The relevance and practical implications which stem from this research are discussed. PMID- 1617472 TI - Child care workers' knowledge about reporting suspected child sexual abuse. AB - As reports of the sexual abuse of preschool-aged children increase and the number of children in day care expands, it is important to recognize child care workers as potentially important resource persons for sexually abused preschoolers. Although they are potential resources for abused children, they may fail to report suspected abuse if they do not know their legal responsibilities and their rights and protections under the law. The purpose of this study was to determine child care workers' knowledge about their reporting rights and responsibilities. Relative to child sexual abuse experts, day care personnel knew significantly less about the procedures for reporting suspected abuse and their protection under the law. Suggestions for improving child care workers' knowledge about reporting suspected sexual abuse cases are provided. PMID- 1617473 TI - Sexual abuse trauma among professional women: validating the Trauma Symptom Checklist-40 (TSC-40). AB - This study examines the usefulness of the Trauma Symptom Checklist (TSC-40) in measuring the long-term sequelae of sexual abuse. In a national survey of 2,963 professional women, the TSC-40 was found to be reliable and to display predictive validity with regard to childhood sexual victimization. Women who reported a sexual abuse history scored significantly higher than did women with no history of abuse on each of the six subscales and on the overall TSC-40 score. Various aspects of childhood victimization were associated with the subscale scores, with the Sexual Abuse Trauma Index and Dissociation subscales being more sensitive to the specific components of the abuse. PMID- 1617474 TI - A retrospective study of long-term methods of coping with having been sexually abused during childhood. AB - Methods of coping with childhood sexual abuse were retrospectively studied in a community sample of 54 adult women who had been sexually abused in childhood. From the time the abuse ended until the present, "denial" and "emotional suppression" were the coping methods most commonly employed of the nine methods measured. One purpose of this study was to determine if the methods used to cope with the aftermath of being sexually abused during childhood were associated with current psychological adjustment beyond what could be predicted by the characteristics of the abusive experience per se. A partial correlation analysis and a multiple regression analysis suggested that avoidant/emotion suppressing coping strategies although frequently used and rated by subjects as helpful, were in fact associated with poorer adult psychological adjustment. PMID- 1617475 TI - Effects of older brother-younger sister incest: a study of the dynamics of 17 cases. AB - The purpose of this study was to explore the effects of older brother-younger sister incest from the perspective of the women who experienced it in childhood or adolescent years. Dynamics in the families-of-origin were also explored, as these related or contributed to the effects from the incest. Seventeen women were interviewed, using an in-depth, semi-structured interview. Four self-report objective instruments were also administered that measure dynamics in the family of-origin and symptomatology that is often associated with the effects of trauma. Interview and objective data were analyzed by systematically organizing the women's perceptions and conceptualizations into common themes. All of the women's families of origin were described as dysfunctional. Common effects reported included mistrust of men and women, chronic low or negative self-esteem, sexual response difficulties, and intrusive thoughts of the incest. Women regarded individual therapy, talking with supportive family and friends, and validating themselves as victims at the time of the incest as ways in which they have helped themselves to deal with the effects of the incest. These results have important implications for therapy, including serious consideration of the impact and contribution of this kind of incest on reported symptomatology, and on emerging issues and conflicts in the therapeutic process. PMID- 1617476 TI - Use of anatomical dolls by Boston-area professionals. AB - Anatomical dolls are a widely used but controversial tool for interviewing child victims of sexual abuse. The present research examines how a representative sample of professionals who evaluate children actually use the dolls. Contrary to past reports, the results revealed that 96.6% of professionals who use the dolls had received training in anatomical doll use, 77.8% followed some standard protocol for interviewing, and 97.3% had at least 1 year of experience with anatomical dolls. The results also revealed that the majority of professionals did not engage in the "leading" behaviors of presenting unclothed dolls to children or undressing the dolls for the child, again contrary to past reports. The present research indicates that the professionals in this sample are more experienced and better trained than is typically thought. PMID- 1617477 TI - Relationships between perceived parental acceptance-rejection, psychological adjustment, and substance abuse among young adults. AB - This study examined the relationship between perceived parental acceptance rejection, psychological adjustment, and substance abuse. A volunteer sample of 40 young adult substance abusers was compared to a comparable volunteer sample of 40 nonabusers with respect to individuals' perceptions of paternal and maternal acceptance-rejection and psychological adjustment. Discriminant function analysis using the jackknife procedure was utilized to examine the predictive power and the classification accuracy of perceived parental acceptance-rejection and psychological adjustment. Results of the research show that: (a) Both perceived paternal and maternal rejection in childhood tend to be significantly higher among substance abusers than among nonabusers, and; (b) substance abusers are more impaired in their current psychological adjustment than are nonabusers. These two classes of predictor variables yield a correlation of .77 with group membership (i.e., abusers vs. nonabusers), and the three predictor variables successfully discriminate substance abusers from nonabusers with jackknifed classification accuracy of 87.5%. Adding the demographic variable "education level" to the model raises the jackknifed classification accuracy to 91.2%, yielding only seven misclassifications in the total sample of 80 volunteers. PMID- 1617478 TI - The youth protection program of the Boy Scouts of America. PMID- 1617479 TI - Anatomical doll play of preschooler referred for sexual abuse and those not referred. PMID- 1617480 TI - [Purification of lipase from latex of Euphorbia characias by an extraction method with apolar solvent]. AB - A lipase from the latex of Euphorbia characias was purified using a new method involving extraction by apolar solvent and adsorption chromatography on silica. The lipase (specific activity 1,500 IU/mg of protein) was eluted from silica complexed with a lipid. The main proteic fraction, showing a molecular weight of 38,000, was inactive when dissociated from the lipid fraction. It was necessary to reassociate the lipid and proteic fractions for 72% of the lipolytic activity to be recovered. PMID- 1617482 TI - Purchasers, providers and contracts--here to stay? PMID- 1617481 TI - [New data on a second endogenous molecular form of mammalian hypothalamic LHRH, (hydroxyproline 9) LHRH]. AB - An endogenous hydroxylated form of LHRH, (Hyp) LHRH, is able to displace LHRH bound to pituitary membrane preparations. In parallel, it stimulates release of both LH and FSH from pituitary cells in primary culture. The potency ratio of (Hyp)LHRH is approximately 1:20 and 1:5 with respect to the native decapeptide when peptidasic degradation is or is not inhibited. This correlates with a greater resistance of (Hyp) LHRH towards enzymatic degradation; in contrast to LHRH, the C-terminal (residues 6 to 10) end of (Hyp) LHRH is not degraded and generates C-terminal fragments which account for 64% of the LHRH immunoreactivity in extrahypothalamic areas as the hippocampus. Besides its weak gonadotropin releasing activity and its action or its localization in peripheral organs (placenta, gonads), a major role of the hydroxylated decapeptide may thus be to serve as a precursor of smaller active fragments on targets other than pituitary receptors. PMID- 1617483 TI - Some social correlates with the dental health of young children. AB - A socio-dental investigation was carried out among 405 five-year-old school children living in a predominantly rural area of West Wales. Information was gathered from a clinical examination of the children and a questionnaire to their parents. The replies to the questionnaires were then cross-tabulated with the clinical findings. The results indicated that lower dmft values were positively associated with household ownership of a telephone and a car and a higher educational attainment by mothers. Mothers with a high level of anxiety about a dental visit and an expectation of eventual edentulousness tended to be the parents of the children with the highest level of untreated carious teeth. The importance of a family pattern of service use is also demonstrated. PMID- 1617484 TI - Preventive oral health related behaviour of dentally anxious schoolchildren aged 13-14 years in Lothian, Scotland. AB - The aim of this study was to determine the self-reported preventive oral health related behaviours of dentally anxious schoolchildren. 1103 children participated in the study, mean age 14 years (SD 0.35 years), and the prevalence of high dental anxiety was 7.1 per cent (95 per cent confidence interval = 5.6 per cent, 8.6 per cent). Children with high self reported dental anxiety were more likely to defer, cancel and or not attend dental appointments. In addition, for this group the last dental visit was more likely to be as a result of pain and less likely to have been for a dental examination only. Overall dentally anxious children did not help themselves by keeping their teeth clean. Fluorides were infrequently used by all the children, and only 12 per cent of all who participated in the study used fluoride supplements regularly. In this context it is not surprising that no differences in present or past use of fluoride supplements could be determined between high and low/moderate dental anxiety groups. The high dental anxiety group spend significantly more (median = 50p) on sweets per day and drank more cans of fizzy drinks (median = 2) compared with the low/moderate anxiety groups. These effects were significant after taking into account social class and gender differences. It was clear from the study that even when social class and gender are taken into account the children with high dental anxiety were not helped by their relatively poor attitudes towards preventing disease in their own mouths. PMID- 1617485 TI - Caries-risk-reducing effects of xylitol-containing chewing gum and tablets in confectionery workers in Finland. AB - Two-hundred and thirty-two workers who had taken part in a comprehensive study on occupational risks in the Finnish confectionery industry and who were still in the same employment, were tested for their willingness to use xylitol-containing products for caries prevention and for the effects of voluntary use of these products on their caries-promoting salivary characteristics. Xylitol-sorbitol chewing-gum and xylitol tablets were provided at the places of work for free use over a three-month period. The consumption was measured, the workers were asked for their opinions of the xylitol, and the effects of the products used on salivary characteristics were studied by means of a caries-risk index. Eighty-six per cent of the workers on the production lines reported having used xylitol containing products during the study period. About 70 per cent consumed on average either 6.9 pieces of chewing-gum (range 0-20) or 1.2 tablets (range 0-15) per day. Eighty-one per cent thought that use of xylitol was good for their dental health. Five per cent thought the opposite. Use of xylitol-containing products was found to increase salivary flow and salivary buffer capacity of the subjects. A decrease in the number of workers with high salivary S. mutans count was observed. On examining shifts from risk groups to non-risk groups, a statistically significant positive change was noted. The results indicate that an ordinary commercial xylitol-containing chewing-gum can be used to decrease caries risk factors in confectionery workers. PMID- 1617486 TI - Prediction of costs in a selective caries prevention programme. AB - A method is proposed for the prediction of the costs of a selective caries prevention programme; that is one where preventive treatment is given only to individuals who have been classified as at high risk of caries. A person so identified may be correctly classified as "high risk" or misclassified as "low risk". Similarly, a person at low risk may be correctly classified or misclassified as high risk. Therefore costs have to be calculated for each of the four situations, and expected frequencies of all four possible classifications have to be taken into account. After the identification of a logistic regression model which permits the prediction of whether a child will experience a high caries increment, sensitivity (SN) and specificity (SP) can be calculated for a set of different decision rules (critical scores, cutpoints or cut-off points Pcp). An example is presented in detail to demonstrate how the expected costs etc. for a specified prevention programme can be calculated without additional effort. The plotting of SN, SP and measures of costs as functions of Pcp permits the anticipation of expected effects of a caries prevention programme and helps to choose the appropriate cutpoint. Such plots may be helpful when comparing different caries prevention programmes and when deciding whether such a programme should be started. PMID- 1617487 TI - Assessment of orthodontic treatment needs by teenagers in an Asian community in Singapore. AB - The purpose of this study was to determine (1) the preference of dental occlusion types among teenagers, and (2) their assessment of the necessity for orthodontic treatment. A total of 1189 teenagers (mean age 15.3 +/- 3.2 years) were asked to rank a series of colour photographs of seven occlusion types. Their ranking, in descending order of attractiveness, were as follows: Class I occlusion, anterior open bite, Class III occlusion, Class II occlusion, anterior spacing, anterior crowding and deep bite occlusion. The perceived need for treatment was found to be inversely correlated with the rank order of attractiveness. There appeared to be no statistical difference (P less than 0.05) in the perception for treatment among different racial and income groups. However, with the exception of anterior open bite and deep overbite occlusions, a statistically significant (P less than 0.05) greater number of females than males perceived a need for treatment. Assessment of occlusal disharmonies among teenagers could provide clinicians and health care personnel with an indication of the relative attractiveness among occlusion types and hence the establishment of treatment priorities. PMID- 1617490 TI - Heritage and dentistry: a comparative analysis of the cultural determinants of professional status. PMID- 1617489 TI - Dentistry in Japan. PMID- 1617491 TI - Information needs for monitoring dental health and for planning local dental services. AB - The working party was established by the Council of The British Association for the Study of Community Dentistry in response to health circular HC(89)2 and its equivalents in areas other than England, to consider the information necessary to monitor the dental health of adult populations and for planning local dental services. Recommendations are made as to the type of information required and its availability. A key issue is the definition of local geographical units suitable for planning purpose. Effective collaboration between District Health Authorities and Family Health Services Authorities is essential in achieving in agreed approach which is the foundation of a comprehensive information system. Information for monitoring the dental health of the population and for planning dental services should include data on local demography, the needs, demands and expectations of the population, the local availability of dental services and the distribution of facilities, and the activity of dentists and the uptake of dental care. It is the view of the working party that much useful information about adult dental health can be obtained from the use of self-reporting questionnaires and that clinical examinations are not generally required. However there are circumstances which may justify the collection of clinical data and it is desirable that such studies are conducted in a manner which permits comparisons. Criteria for the standardised clinical assessment of adult dental health have been prepared and it is recommended that these are adopted for general use. Further research is required to test and validate appropriate questions for inclusion in self reporting studies. This should lead to the selection of a set of core questions which can be widely used to allow local and regional comparisons of adult dental health. PMID- 1617488 TI - Knowledge of AIDS and HIV infection displayed by Tanzanian operating dental staff in 1988 and 1989: a follow-up study. AB - In many urban areas of Central and Eastern Africa 20-30 per cent of the sexually active population has been infected with HIV. It can be assumed that every member of the operating dental staff in Tanzania frequently treats HIV-positive patients. The knowledge of AIDS and HIV infection was investigated by Tanzanian dental teams in 1988 and 1989. In both years almost one quarter of the dental officers and half the other operating team members chose incorrect information about the methods of transmission of HIV. Several respondents named health care workers as belonging to a high risk group. Fever and loss of weight were known to be early symptoms of AIDS. In 1989, when asked to identify oral manifestations of HIV, one quarter of all the dental staff could not mention any of them. The findings of the study emphasise the need for urgent further education of dental teams in Tanzania. PMID- 1617493 TI - A comparison of two dual-energy X-ray absorptiometry systems for spinal bone mineral measurement. AB - Two dual-energy X-ray absorptiometry (DEXA) systems--the Hologic QDR-1000 and the Norland XR-26 bone densitometers--were evaluated in terms of precision, accuracy, linearity of response, X-ray exposure, and correlation of in vivo spinal measurements. In vitro precision and accuracy studies were performed using the Hologic anthropomorphic spine phantom; linearity of response was determined with increasing thicknesses of aluminum slabs and concentrations of Tums E-X in a constant-level water bath. Both systems were comparable in precision, achieving coefficients of variation (CVs) of less than 1% in bone mineral content (BMC, g), bone area (cm2), and bone mineral density (BMD, g/cm2). Both were accurate in their determination of BMC, bone area, and BMD with reference to the Hologic spine phantom. Both systems also showed good BMC and BMD linearity of response. Measured X-ray skin surface exposures for the Hologic and the Norland systems were 3.11 and 3.02 mR, respectively. In vivo spinal measurements (n = 65) on the systems were highly correlated (BMC: r = 0.993, SEE = 1.770 g; area: r = 0.984, SEE = 1.713 cm2; BMD: r = 0.990, SEE = 0.028 g/cm2). In conclusion, both systems are comparable in terms of precision, accuracy, linearity of response, and exposure efficiency. PMID- 1617492 TI - Cytokines, hematopoiesis, osteoclastogenesis, and estrogens. PMID- 1617494 TI - Bioavailability of fluoride in postmenopausal women: comparative study between sodium fluoride and disodium monofluorophosphate-calcium carbonate. AB - Fluoride (F) increases trabecular bone mass and can be used in the treatment of osteoporosis with crush fractures. As the bioavailability of sodium fluoride (NaF) can be impaired by concomitant absorption of calcium, both drugs have to be ingested separately. However, disodium monofluorophosphate-calcium carbonate (MFP Ca), another F compound, allows a single administration. In a cross-over randomized study, we compared the bioavailability of both drugs under regular conditions of prescription. Ten postmenopausal women (aged 48-77 years) with glomerular filtration rate (GFR) greater than 70 ml/minute and without bone disease entered the study. Each received 25 mg of NaF [i.e., 11.3 mg F ion (F-)] fasting and 100 mg of Na2FPO3-1250 mg CaCO3 (i.e., 13.2 mg F-) with breakfast in a single dose separated by an 8-day washout. After dosing, plasma F levels and fractionated and total urinary F collection were determined during a 24-hour period using a specific electrode. Results show a significant shorter lag time absorption (Tmax = 1.4 +/- 0.2 hour) and a higher maximal concentration (Cmax = 260 +/- 60 ng/ml) for MFP-Ca than for NaF (Tmax = 2.5 +/- 0.4 hour; Cmax = 200 +/ 85 ng/ml). However, areas under curve (AUC) for MFP-Ca (1711 +/- 195 micrograms/liter/hour) and for NaF (1202 +/- 147 micrograms/liter/hour) were not significantly different. The relative bioavailability of both F compounds related to their fluoride content (i.e., 1.22 for AUC ratio) was equivalent, according to the Westlake method. These data provide the first evidence of comparable bioavailability of two F compounds in a population of postmenopausal women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617495 TI - Effects of combined and separate intermittent administration of low-dose human parathyroid hormone fragment (1-34) and 17 beta-estradiol on bone histomorphometry in ovariectomized rats with established osteopenia. AB - To evaluate the potential use of a combination of parathyroid hormone (PTH) and estrogen as therapy for osteoporosis, we examined the effects of combined and separate administration of low-dose PTH and estradiol in ovariectomized rats with established osteopenia. Ovariectomized rats were untreated for 5 weeks after surgery and then injected s.c. with vehicle (Ovx + V), 1-34 hPTH (2.5 micrograms/kg/day) (Ovx + P), 17 beta-estradiol (50 micrograms/kg/day) (Ovx + E), or a combination of these (Ovx + P + E), for a further 4 weeks. We found no differences in serum calcium, tubular reabsorption of phosphate, or 25OHD. 1,25(OH)2D levels were significantly higher in Ovx + P and lower in Ovx + E, when compared with Ovx + V. Though there was no change in bone mineral density (BMD) in the diaphysis region of femurs, reduction of BMD in the distal region of the femurs in Ovx + V was reversed in Ovx + E and Ovx + P + E. Compared with Ovx + V, Ovx + P and Ovx + P + E had significantly higher cancellous bone volume (Cn BV/TV) whereas Ovx + E showed a nonsignificant increase. When indices of bone turnover were examined, PTH alone showed a small but not significant improvement in bone formation rate (BFR). Increased osteoclast surface (OCS), as the result of ovariectomy, was inhibited in Ovx + E and Ovx + P + E. Estrogen alone (Ovx + E) severely inhibited BFR, but co-administration of PTH and estrogen (Ovx + P + E) showed an impressive reversal of such inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617496 TI - Regulation of bone turnover and prevention of bone atrophy in ovariectomized beagle dogs by the administration of 24R,25(OH)2D3. AB - In order to determine whether the administration of 24R,25(OH)2D3 had any beneficial effect on the regulation of bone turnover and the prevention of bone atrophy, we examined beagles for 31 months after ovariectomy (OVX). Fourteen beagle dogs (8.54 +/- 1.22 kg body wt-b.w.) were divided into four groups. Group 1 (n = 3) was the sham, and Group 2 (n = 3) served as the OVX control. In Group 3 (n = 4) and Group 4 (n = 4), 24,25-dihydroxyvitamin D3(24R,25(OH)2D3) was given daily at dose levels of 2 and 10 mcg/kg B.W., respectively. In Group 4, the dose level was increased to 100 mcg/kg by 17 months. During the experiments, urinary hydroxyproline (U-HPr), serum chemistry, serum bone gla-protein (BGP), and vitamin D metabolite levels were monitored. At the end of the experiment, bone mineral content (BMC) in the 6th and 7th lumbar vertebrae and right femur was determined by single photon absorptiometry. The left iliac bone sample was obtained after tetracycline labeling, and undecalcified sections were observed. In Group 2, excretion of U-HPr increased after OVX and had reached a level of approximately twice the baseline values by 10 months; then it gradually came down to the original level. In Group 3, however, U-HPr excretion remained at the same level as the baseline value, as it did in Group 1. In Group 4, it was remarkably reduced down to 50-60% of the baseline values. Serum BGP level was markedly reduced in Group 4. Serum 24,25(OH)2D levels were markedly increased in Groups 3 and 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617497 TI - Vitamin D metabolites prevent vertebral osteopenia in ovariectomized rats. AB - The present study investigated the prophylactic effects of vitamin D metabolites and vitamin D metabolite combinations on static and dynamic, tetracycline-based, histomorphometric parameters in the axial skeleton of ovariectomized rats. Forty three Fischer-344 rats (10 weeks old, 130 g each body weight, BW) were either bilaterally ovariectomized (OVX) or sham-operated (SHAM). The rats were allocated into the following groups: SHAM; OVX; OVX + 7.5 ng 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3]/rat/day; OVX + 15 ng 1 alpha,24R,25-trihydroxyvitamin D3 [1,24,25 (OH)3D3]/rat/day; OVX + 75 ng 24R,25-dihydroxyvitamin D3 [24,25(OH)2D3]/rat/day; OVX + 7.5 ng 1,25(OH)2D3/rat/day + 15 ng 1,24,25(OH)3D3/rat/day; OVX + 7.5 ng 1,25(OH)2D3/rat/day + 75 ng 24,25(OH)2D3/rat/day. The vitamin D metabolites were fed orally starting 4 weeks after surgery. Urine and blood samples were collected 12 and 16 weeks postovariectomy, respectively. Sixteen weeks after surgery, all rats were sacrificed, and the first lumbar vertebrae were processed undecalcified for histomorphometric analysis. Ovariectomy induced a highly significant reduction (P less than 0.001) of cancellous bone mass in the secondary spongiosa of the lumbar vertebral body. The bone loss in OVX rats was accompanied by a distinct elevation of all histomorphometric parameters of bone formation and resorption. 1,25(OH)2D3 and both vitamin D metabolite combinations significantly raised serum calcium levels and prevented the bone loss by inhibiting the increased bone resorption in OVX rats. In the applied dosage, 1,24,25(OH)3D3 and 24,25(OH)2D3 alone were ineffective in preserving the cancellous bone of the lumbar vertebra in OVX rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617498 TI - Development of monoclonal antibodies to parathyroid hormone-induced resorptive factors from osteoblast-like cells. AB - Parathyroid hormone (PTH) induces osteoblast-like cells to secrete factors capable of increasing cellular bone resorption; these factors are extremely labile. We have partially isolated them from supernatants of PTH-stimulated ROS 17.2 cells using affinity chromatography. Products eluted from the matrix, carboxymethyl cellulose covalently linked to Cibacron Blue F3GA, (CM-AB) were used as immunogens in mice. Serum from these mice blocked the effect of PTH stimulated supernatants in a bioassay for bone resorption (the bone rudiment system). Then, hybridomas were produced from spleen cells of these mice. Screening of these hybridoma cultures revealed a consistent blocking effect of supernatants at a dilution of 1:100 in the bioassay. At higher dilution (1:1000), however, fewer culture supernatants blocked this effect in the bioassay. Mixed hybridoma cultures have been cloned and subcloned. Evaluation of the resulting hybridoma supernatants revealed that supernatants from at least three clones were necessary to neutralize the effect of the PTH-induced, osteoblast-produced resorption factors in organ culture. Similarly, using sucrose density gradient analysis, it is necessary to use three antibodies to bind all the 35S-labeled protein from supernatants of PTH-stimulated ROS cultures (equivalent to the fraction used as immunogen in the mice). The effect of PTH in organ culture is blocked by this same group of hybridoma supernatants. The antibodies appear specific for osteoblast-like cell resorption factors, as they do not block the effect of PTH on cAMP accumulation in ROS cell cultures. On the other hand, they do block the effects of dibutyryl cAMP on resorption in organ culture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617499 TI - Effects of long-term daily administration of prostaglandin-E2 on maintaining elevated proximal tibial metaphyseal cancellous bone mass in male rats. AB - The effects of long-term prostaglandin E2 (PGE2) on cancellous bone in proximal tibial metaphysis were studied in 7-month-old male Sprague-Dawley rats given daily subcutaneous injections of 0, 1, 3, and 6 mg PGE2/kg/day and sacrificed after 60, 120, and 180 days. Histomorphometric analyses were performed on double fluorescent-labeled undecalcified bone specimens. After 60 days of treatment, PGE2 produced diffusely labeled trabecular bone area, increased trabecular bone area, eroded and labeled trabecular perimeter, mineral apposition rate, and bone formation rate at all dose levels when compared with age-matched controls. In rats given PGE2 for longer time periods (120 and 180 days), trabecular bone area, diffusely labeled trabecular bone area, labeled perimeter, mineral apposition, and bone formation rates were sustained at the elevated levels achieved earlier at 60-day treatment. The eroded perimeter continued to increase until 120 days, then plateau. The observation that continuous systemic PGE2 administration to adult male rats elevated metaphyseal cancellous bone mass to 3.5-fold of the control level within 60 days and maintained it for another 120 days indicates that the powerful skeletal anabolic effects of PGE2 can be sustained with continuous administration. PMID- 1617500 TI - Effect of different phospholipid-cholesterol membrane compositions on liposome mediated formation of calcium phosphates. AB - The present report compares the effects of different membrane phospholipid (PL) cholesterol compositions on the kinetics of liposome-mediated formation of calcium phosphates from metastable solutions (2.25 mM CaCl2; 1.5 mM KH2PO4) at 22 degrees C, pH 7.4 and 240 mOsm. In most experiments, the liposomes were composed of 7:2:X mixtures of phosphatidylcholine (PC), neutral or acidic phospholipids, and cholesterol (Chol, X = 0, 10, 35, or 50 mol%). The neutral phospholipids (NPL) examined, in addition to PC, were phosphatidylethanolamine (PE) and sphingomyelin (Sph), and the acidic phospholipids (APL) examined were dicetylphosphate (DCP), dioleolylphosphatidylglycerol (DOPG), dioleolylphosphatidic acid (DOPA), phosphatidylserine (PS) and phosphatidylinositol (PI). The 7:2:X liposomes did not initiate mineralization in metasable external solutions per se or, with the exception of DOPA, show extensive Ca-PL binding. However, solution Ca2+ losses due to precipitation occurred when the liposomes were encapsulated with 50 mM KH2PO4 and made permeable to external Ca2+ with X-537A. The extent of these Ca2+ losses was sensitive to both the phospholipid and Chol makeup of the membrane. Moderate-to extensive intraliposomal precipitation occurred in all 7PC:2APL and 7PC:2NPL liposomes containing 0 or 10 mol% Chol. In contrast, at 50 mol% Chol, mineralization inside all liposomes was negligible. The only significant discriminating effect on internal mineralization among the different phospholipids was observed at 35 mol% Chol, where mineral accumulations ranged from negligible to moderate. At 0 or 10 mol% Chol, extraliposomal precipitation was extensive in all but DOPA- and PS-containing liposomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617501 TI - Liposome interactions with hydroxyapatite crystals: a possible mechanism in the calcification of atherosclerotic plaques. AB - Some stages in the calcification of atherosclerotic plaques may involve associations between lipids and hydroxyapatite (HA) by surface interactions. Liposomes, artificial membranous lipid vesicles, have been used in this study as model structures for biological calcification processes. Liposome (containing cholesterol and phosphatidylcholine in most cases) suspensions were prepared by sonication, after which HA seed crystals were added to the suspensions and stirred at 37 degrees C. Aliquots of the liposome suspensions were analyzed for particle size distribution and by transmission electron microscopy and electron diffraction. The results showed that HA induced aggregation of liposomes and modifications of the microscopic shapes of the liposomes in the aggregates. These data can be explained by the electron diffraction pattern where superimposition of liposome reflection and crystal reflection exists and may suggest organic inorganic interaction. The potential of HA crystals to induce formation of liposome aggregates may be seen as a step in atherosclerotic plaques calcification. PMID- 1617502 TI - Changes in the solubility of enamel mineral at various stages of porcine amelogenesis. AB - The solubility of enamel mineral (a carbonated apatite) formed at various stages of porcine amelogenesis was investigated at controlled partial pressures of CO2. Enamel samples were obtained from the outer (young) secretory, inner (old) secretory, early (soft) and late (hard) mature enamel of the permanent dentition of slaughtered piglets. The dissected enamel was pulverized and subjected to a plasma ashing at low temperature to remove organic matter. The composition (Ca, total P, HPO4, and CO3) of the enamel mineral was determined chemically. The enamel mineral contained significant amounts of carbonate and acid phosphate; the model adopted for its stoichiometry was [Ca]5-x [HPO4]v[CO3]w[PO4]3-x[OH]1-x. Each enamel sample was equilibrated in dilute phosphoric acid solutions (0.01-1.2 mM) under Pco2 = 1.86 and 1.75%. Equilibration of the enamel samples usually took 20-25 days; the solution composition (pH, concentrations of Ca, P, Mg, Na, and K, and activity of Ca2+) was determined periodically. The composition of the solution at equilibrium showed that (1) the outer (younger) secretory mineral was the most soluble and the solubility of enamel mineral decreased with advancing developmental stages; (2) the mean activity product in the saturated solutions for the outer secretory enamel was the same as that calculated on the basis of the reported composition of the enamel fluid; and (3) the solubility data obtained with most of the enamel samples were consistent with a model in which the equilibration includes two processes: dissolution of the original enamel mineral and precipitation of a new carbonatoapatite. Analyses of the equilibrated samples, particularly the mature enamel, by electron microscopy, supported the precipitation of carbonatoapatite.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617503 TI - Localization of malachite green positive lipids in the matrix of bone nodule formed in vitro. AB - An electron histochemical study was carried out on bone nodules formed in vitro in collagenase-released calvarial cells in order to visualize the lipid components of the extracellular matrix (EM). The malachite green aldehyde fixative technique, which allows both preservation and staining of some phospholipids of the extracellular matrix, was used. Controls were performed on sections demineralized, and then submitted to lipid extraction with a chloroformmethanol mixture (2/1 v/v) and to glycosaminoglycans digestion with 0.5% bovine testicular hyaluronidase to verify specificity for lipid staining. This allowed us to visualize the lipids (1) in the osteoid as granules associated to ribbon-like structures connected to the collagen fibers, (2) as electrondense deposits seen as dots on the outer surface membrane of the matrix vesicles, and (3) in the mineralized matrix as roundish patches formed of needle-shaped materials and at the mineralization front as individual ones. This study demonstrated that at the EM level, the lipids are present in the osteoid at locations very similar to what have been observed for the glycosaminoglycans, and in the mineralized matrix as components of the crystal ghosts. PMID- 1617504 TI - The role of morphogens in endochondral ossification. AB - The formation of bone occurs normally by one of two developmental processes: intramembranous or endochondral ossification. Endochondral ossification occurs in the morphogenesis of the limb buds and growth plates, and in the regeneration of bone following injury (fracture callus). Two classes of diffusible morphogen-like molecules (MLMs) involved in limb development are the bone morphogenetic proteins (BMPs) and retinoic acid (RA). These MLMs are associated, respectively, with the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) of the primitive limb bud. They function as potent regulators of pattern formation and are involved in tissue proliferation and differentiation. The presence of endochondral ossification in fracture callus suggests a role for MLMs in that process as well. To date, virtually nothing is known about the role of morphogens in the regeneration of bone (fracture healing). In this article, we review the current knowledge of MLMs in bone formation and propose a theory on their role in fracture healing. We hypothesize that MLMs involved in fracture healing may also express spatial and temporal information. A more complete understanding of the role of morphogens in both limb development and fracture healing is of major importance to practicing orthopedists and their patients. PMID- 1617505 TI - Measurement of bone cell metabolism in vitro using mass spectrometry. AB - The metabolism of bone cells can be monitored directly and continuously 'in vitro' by a new technique, based on mass spectrometry. The consumption of oxygen and production of carbon dioxide were measured in 6 different cultures of human bone cells. The method was feasible for measurement of bone cell metabolism and was also tested in suspensions of hepatocytes. The data obtained with these cells were comparable to results obtained with traditional techniques, and a relation to cellular concentration was demonstrated. PMID- 1617506 TI - Etiology of Paget's disease of bone: a new perspective. PMID- 1617507 TI - Exercise and cardiovascular health. PMID- 1617508 TI - Coronary thrombolysis--persisting uncertainties about optimal regimens and patient selection. AB - A tremendous body of excellent clinical trial data has provided clinicians with a clear rationale for the use of several thrombolytic agents for patients with acute myocardial infarction. Efficacy over a considerable range of circumstances and patient characteristics has been demonstrated. Nevertheless, many uncertainties remain and are being addressed in further clinical trials. Economic analyses of interventions shown to have clinical efficacy should assist health care planners in decisions as to which of these interventions may be justified expenses as the demands upon the health care dollar increase. PMID- 1617509 TI - Potential cost effectiveness of intravenous tissue plasminogen activator versus streptokinase for acute myocardial infarction. AB - OBJECTIVE: An economic evaluation of the potential incremental benefits of intravenous tissue plasminogen activator (tPA) versus streptokinase (SK) for treatment of acute myocardial infarction. DESIGN: Cost effectiveness analysis from a third-party payer perspective (Ontario Ministry of Health). ECONOMIC INPUTS: Fully allocated costs for cardiovascular procedures and hospitalization for myocardial infarction were obtained anonymously for four Ontario teaching hospitals and converted to 1988 Canadian dollars. Professional charges were taken from the provincial health insurance fee schedule and drug costs obtained from the manufacturers. CLINICAL INPUTS: The baseline analysis was for nonelderly patients with uncomplicated myocardial infarctions; sensitivity analyses allowed extrapolation to higher risk subgroups. Short and longer term mortality and short term invasive procedure rates were estimated using data from clinical trials. MAIN RESULTS: If tPA achieves a 1% short term mortality advantage over SK with no advantages for other survivors, cost per life-year gained can be comparable to other cardiovascular interventions at $58,600. In the absence of immediate survival advantages, but assuming greater left ventricular preservation, the constant annual hazard rate advantage must be about 0.5% per year for competitive cost effectiveness ratios. CONCLUSIONS: A full range of projections is presented to help guide the policy decisions that will arise in the wake of the Global Utilization of SK and tPA for Occluded Coronary Arteries (GUSTO) trial. The analysis also illustrates the general importance of considering longer term effects of in-hospital therapies for acute myocardial infarction. PMID- 1617510 TI - Effects of a fish oil supplement on blood pressure and serum lipids in patients treated for coronary artery disease. AB - OBJECTIVE: The purpose of this study was to evaluate the effects of a concentrate of fish oil on blood pressure and serum lipids in patients treated for coronary artery disease. DESIGN: One hundred and twenty-five patients were randomly assigned to receive 15 g/day MaxEPA (4.5 g eicosapentaenoic and docosahexaenoic acids) or olive oil. Blood pressure and serum lipids were measured at enrollment and six months thereafter. MAIN RESULTS: As an important proportion of antihypertensive or antianginal drug users stopped their usual medication during the trial, blood pressure increased in both groups. The increase in systolic blood pressure was less in the fish oil group than in the control group (P = 0.002). Serum triglyceride levels decreased markedly in the fish oil group while they remained constant in the control group (P = 0.0001). Fish oil supplementation had no effect on total cholesterol and only marginal independent influence on high density lipoprotein and low density lipoprotein cholesterol levels. CONCLUSIONS: In conclusion, fish oil supplementation has a beneficial effect on blood pressure and serum triglycerides in patients treated for coronary artery disease. PMID- 1617511 TI - Pheochromocytoma: an unusual presentation and sequela. AB - A 40-year-old male presenting with exercise-induced headaches was found to have a pheochromocytoma which was subsequently removed. His blood pressure was never recorded as elevated. He went on to develop recurrence of asthma, which had been absent for at least 20 years, 48 h postoperatively. This is the first case of pheochromocytoma manifesting as exercise-induced headache in the absence of detectable hypertension. PMID- 1617512 TI - [Sudden death in leukemic patients treated with doxorubicin]. AB - Cardiotoxicity of the anthracycline antineoplastic drugs is well known, especially the chronic effects, manifested mainly as congestive heart failure. Fewer reports have been published about the acute cardiotoxicity of these medications, and risk factors associated with their use. Two cases of malignant arrhythmias leading to sudden death associated with severe hypokalemia are reported. These cases suggest a synergistic effect between anthracyclines and electrolyte disorders resulting in the acute cardiotoxicity of these drugs. The administration of these antineoplastic drugs should include regular and systematic control of serum electrolytes and correction of hypokalemia during treatment. PMID- 1617513 TI - Left ventricular mural bacterial endocarditis: diagnosis by transesophageal echocardiography. AB - An unusual case of staphylococcal endocarditis with a vegetation attached to the left ventricular myocardium is described. No valvular vegetations are present. The diagnosis was made by transesophageal echocardiography. The patient had no chronic debilitating disease, nor was she immunosuppressed. PMID- 1617514 TI - The cellular electropharmacology of mexiletine in papillary muscles of guinea pigs chronically treated with amiodarone. AB - OBJECTIVE: The combination of mexiletine and amiodarone has proved useful in the control of serious ventricular arrhythmias, but the electrophysiological basis for their effectiveness in combination is unknown. The objective of this study was to compare the effects of mexiletine on action potential parameters of papillary muscles taken from guinea pigs chronically treated with amiodarone, with tissue taken from a control group. DESIGN: The effects of 12.5 to 200 microM mexiletine on action potential parameters of papillary muscles taken from guinea pigs chronically treated with amiodarone were compared with tissue taken from a control group, at frequencies of 1.0, 1.5 and 3.0 Hz, using standard microelectrode techniques. Onset of use-dependent block was assessed by 30 beat trains, and recovery from block by extrastimuli at diastolic intervals ranging from 200 to 5000 ms at both 1.5 and 3.0 Hz. ANIMALS: Eighteen four-week-old guinea pigs were randomly divided into two groups. One group received amiodarone in a loading dose of 20 mg/kg/day by intraperitoneal injection for one week, followed by 10 mg/kg/day for 15 weeks. The control animals were given equivalent volumes of dextrose intraperitoneally for 16 weeks. MAIN RESULTS: Mexiletine depressed the maximum rate of depolarization of phase 0 of the action potential (Vmax) in a concentration- and use-dependent fashion. Whereas chronic amiodarone treatment did not alter steady-state Vmax values, the extent of tonic Vmax depression induced by mexiletine was decreased, while use-dependent depression was increased. Mexiletine combined with amiodarone increased effective refractory period prolongation from 306.7 +/- 27.2 to 348.8 +/- 37.2 ms, while action potential duration shortening of mexiletine was moderated from 134.0 +/- 19.8 to 151.0 +/- 8.3 ms (to 90% repolarization at 3 Hz in the presence of 200 microM mexiletine). PMID- 1617515 TI - "Not on the outward appearance .... but on the heart." Matthew Baillie and cardiology. AB - The work of Matthew Baillie (1761-1823), pathologist and physician, is presented with particular relation to the cardiovascular system. Baillie wrote the first systematic textbook of morbid anatomy in the English (or any other) language, and commissioned a book of elegant and accurate illustrations by William Clift (1775 1849). Baillie laid down the anatomical groundwork on which the subsequent generation of physicians built an accurate knowledge of cardiovascular disease. His textbook was widely translated, and influenced medical students and physicians over the first half of the 19th century. His influence on morbid anatomy was similar to that of Vesalius on the science of normal anatomy. PMID- 1617516 TI - Heartbeat--the rhythm of health. World Health Day 1992 focuses on cardiovascular disease. PMID- 1617517 TI - The safety of pediatric cardiac catheterization in an adult hospital setting. AB - OBJECTIVE: To assess the safety of performing diagnostic and interventional cardiac catheterization of neonates, infants and children in a laboratory located in an adult hospital. DESIGN: Retrospective medical record review. SETTING: Children's Hospital of Western Ontario. PATIENTS: All patients 18 years or younger undergoing cardiac catheterization procedures performed by pediatric cardiologists between January 1986 and December 1989. MAIN RESULTS: The total number of procedures performed was 289. Three major (1%), nine moderate (3%) and 20 minor (7%) complications were documented with none fatal. These rates are comparable with complications documented for larger centres with dedicated pediatric catheterization facilities. CONCLUSION: Although less than ideal, the use of an adult facility for pediatric cardiac catheterization appears to be a safe and reasonable alternative. PMID- 1617518 TI - John Keith lecture 1991. Pediatric cardiology: the practice of paradox? PMID- 1617519 TI - Rescue angioplasty during myocardial infarction has a beneficial effect on mortality: a tenable hypothesis. AB - HYPOTHESIS: Rescue percutaneous transluminal coronary angioplasty (PTCA) reduces mortality during myocardial infarction. OBJECTIVE: To determine if PTCA after failed thrombolytic therapy results in reduced mortality. DESIGN: Twenty-eight patients with a persistently occluded infarct artery following thrombolytic therapy more than 3 h after symptom onset were randomized to rescue PTCA (n = 16) or conservative treatment (n = 12) as part of a prospective randomized trial of reperfusion therapy during myocardial infarction in 184 patients. Hospital mortality was assessed in these groups as well as in the 177 patients with known infarct artery status after initial attempts at reperfusion. MAIN RESULTS: There was one death among the 16 patients in the rescue PTCA group versus four deaths in the 12 patients treated conservatively (P = 0.13). Moreover, the death in the rescue PTCA group occurred in one of three patients in whom the procedure failed. Mortality in the entire study group was 10.3% (19 of 184); 4.2% (six of 142) in patients in whom patency was achieved after thrombolysis and/or PTCA and 34.3% (12 of 35) in those in whom reperfusion was not achieved (P less than 0.001). In patients with anterior myocardial infarction, mortality was 6.7% (four of 60) in those with reperfusion and 47.1% (eight of 17) in those with a persistently occluded artery (P less than 0.001). In patients with inferior myocardial infarction, 2.4% (two of 82) with reperfusion and 22.2% (four of 18) with a persistently occluded artery died (P less than 0.01). CONCLUSIONS: Although the number of patients in the randomized groups was small, the trend toward a lower mortality after rescue PTCA supports the hypothesis that rescue PTCA may be beneficial. The mortality results in relation to presence or absence of reperfusion from the entire study population underscores the importance of achieving patency during myocardial infarction. PMID- 1617520 TI - Lambl's excrescences and papillary fibroelastomas: are they different? AB - OBJECTIVE: To determine if Lambl's excrescences (LEs) and papillary fibroelastomas (PFEs) differ histologically. SETTING: Materials were obtained from post mortem examinations performed at the Ottawa Civic Hospital, a tertiary care teaching hospital in Ottawa, Ontario. DESIGN AND PATIENTS: Hearts with grossly 'classic' PFEs (n = 10) or 'typical' LEs (n = 20) were examined. The patients with PFEs had a mean age of 63.5 years (range 24 to 79), similar to that of 68.1 years (range 47 to 83) for those with LEs. The LEs and PFEs were compared regarding their gross characteristics, sizes, locations and microscopic appearances. MAIN RESULTS: Lesions which were termed LEs had a similar microscopic appearance to grossly categorized PFEs; however, the LEs were smaller and broader-based. Some LEs and PFEs were microscopically indistinguishable. CONCLUSIONS: As LEs and PFEs may be virtually identical microscopically in some instances, separation of these two lesions may be artificial; however, this separation remains useful because it highlights the gross appearances, unusual locations and potential clinical sequelae of papillary fibroelastomas. PMID- 1617521 TI - Interaction between an angiotensin converting enzyme inhibitor, perindopril, and a thiazide diuretic in the spontaneously hypertensive rat. AB - Fifty adult male spontaneously hypertensive rats were randomly allocated to receive daily oral treatment with placebo, hydrochlorothiazide (HCTZ 10 mg/kg) and three different dosages of perindopril (S9490-30.1, 0.3 and 1 mg/kg) administered alone or in combination with HCTZ for two eight-day treatment periods separated by a therapeutic washout period of 13 days. Effect of order of treatment was evaluated in rats receiving perindopril plus HCTZ. Time course of changes in systolic blood pressure, heart rate, 24 h urine volume and urinary excretion of sodium, potassium and chloride were studied and compared for all groups. HCTZ alone and lower dosages of perindopril (0.1 mg/kg, 0.3 mg/kg) were ineffective in lowering elevated systolic blood pressure of the spontaneously hypertensive rat, and there were no significant intergroup differences in urine volume and electrolytes. However, antihypertensive efficacy of lower dosages of perindopril was significantly (P less than 0.01) enhanced when administered in combination with HCTZ. The combined treatment also induced significant (P less than 0.01) diuresis and urinary chloride excretion. No significant effect was seen in heart rate. The dose-effect relationship of the combination confirmed the existence of synergistic antihypertensive action between HCTZ and perindopril in the spontaneously hypertensive rat. PMID- 1617522 TI - Early neonatal death due to an unusual pattern of total anomalous pulmonary venous drainage. AB - Total anomalous pulmonary venous drainage (TAPVD) is an uncommon congenital cardiovascular anomaly caused by failure of the common pulmonary vein to develop a connection with the common atrium in early ontogeny, resulting in persisting connections between pulmonary and systemic venous systems and a left-to-right shunt. This usually occurs via a single, enlarged, well-defined venous channel. The authors present an unusual case of TAPVD with venous obstruction with a profusely arborizing plexus of veins arising from the common pulmonary vein and forming multiple tiny anastomoses with the systemic venous system. This plexus may represent the persistence of an earlier, less involuted embryological form of the primitive pulmonary splanchnic plexus than those found in previously described patterns of TAPVD. PMID- 1617523 TI - Vasodepressor syncope in a cardiac transplant recipient: a case of vagal re innervation? AB - At the time of hemodynamic assessment three years after cardiac transplantation, a patient developed symptoms and signs of a vasodepressor reaction. In addition to sudden deceleration of heart rate, a 26% fall in mean blood pressure and a 36% fall in cardiac output was observed. Subsequent investigations revealed the presence of respiratory sinus arrhythmia, profound heart rate acceleration on standing and an approximately normal heart rate response during the following exercise. Contrary to current thinking, these observations suggest that certain individuals may develop autonomic re-innervation following orthotopic cardiac transplantation. PMID- 1617525 TI - Yet more on the Barer-Stoddart report. PMID- 1617524 TI - Assessment of the cardiac patient for fitness to drive. PMID- 1617526 TI - Relativity and cardiology. PMID- 1617527 TI - Holter monitor recording for the detection of myocardial ischemia: validation of a new recorder and chest lead positions. AB - OBJECTIVE: To validate the Reynolds Tracker II Holter system using newly described lead positions during both upright treadmill exercise and in the recumbent position following exercise. The specific lead positions HL1 and HL2 were chosen to detect anterior and postero-inferior myocardial ischemia, respectively, without interfering with the surgical field in the hypothetical situation of open-heart surgery. Similar lead positions have previously been used to monitor myocardial ischemia during induction of anesthesia, but have never been validated by comparison with 12-lead modified electrocardiogram (ECG) recording. METHODS: To validate the authors' 'chosen' Holter lead positions (HL1 and HL2), both at the fifth intercostal space just lateral to the midclavicular line and on the back, 1.5 cm to the left of the vertebral column, respectively) 49 candidates for routine treadmill exercise testing underwent a simultaneous Holter monitor recording using the described lead positions. DATA ANALYSIS: The Holter ECG recordings were separately analyzed by two physicians unaware of patients' identity. RESULTS: Using the modified 12-lead ECG as the 'gold standard', the sensitivity of Holter for detecting ischemia (defined as 0.1 mV or ST depression lasting at least 60 s) was 77 and 83%, and its specificity was 100 and 92%, respectively, for observers 1 and 2. Most episodes of myocardial ischemia were detected by the modified lead V5 for the 12-lead ECG and by HL1 for the Holter recording. Using the Holter Tracker II system and the chosen lead positions, it was possible to detect successfully most episodes of exercise induced myocardial ischemia. CONCLUSION: Holter monitoring might be useful in detecting perioperative myocardial ischemia. PMID- 1617528 TI - Drug therapy of ventricular tachycardia: a cost comparison of randomized noninvasive and invasive approaches. AB - OBJECTIVE: Economic evaluation of noninvasive (suppression of ventricular arrhythmias detected by ambulatory monitoring) and invasive (suppression of arrhythmias induced by programmed stimulation) approaches to antiarrhythmic drug selection for ventricular tachyarrhythmias. DESIGN/SETTING: Randomized clinical trial/tertiary-care hospital. PATIENTS: Of 124 consecutive patients referred for treatment of symptomatic ventricular tachyarrhythmias, 57 consenting patients were eligible to have drug therapy selected by either noninvasive or invasive approaches. MEASUREMENTS: Costs of initial and follow-up (26 +/- 15 months) admissions for the two groups were compared. This economic evaluation also considered relative efficacies of the approaches using the primary outcome variable of symptomatic, sustained ventricular tachyarrhythmia recurrence (including sudden death). RESULTS: Initial hospitalization for therapy selection was less costly by the noninvasive approach ($6,869 +/- 4,019) than by the invasive approach ($13,164 +/- 6,740) (P less than 0.001). However, the noninvasive approach generated higher follow-up hospital costs ($9,204 +/- 9,217) than the invasive approach ($3,784 +/- 4,944) (P = 0.01). Thus, total hospital costs of the noninvasive ($16,073 +/- 9,423) and invasive approaches ($16,949 +/- 7,174) were equivalent. The two-year actuarial probability of a recurrent, sustained, symptomatic ventricular tachyarrhythmia was greater in noninvasive (0.50 +/- 0.10) than in invasive (0.20 +/- 0.08) approach patients (P = 0.02). CONCLUSIONS: The lower initial hospital costs of the noninvasive approach are offset by greater follow-up costs. Within two years the costs of the two approaches are equivalent. Thus, greater antiarrhythmic efficacy can be achieved by the invasive approach to drug selection without increasing total hospital costs. PMID- 1617529 TI - Epidemiology of congestive heart failure: Canadian data from 1970 to 1989. AB - OBJECTIVE: To assess mortality rates from congestive heart failure in Canada from 1970 to 1989. DESIGN: Observational, retrospective design using national population and mortality data. MAIN RESULTS: There is a definite age gradient for deaths from congestive heart failure which, combined with a general ageing of the Canadian population, has lead to an increase in the absolute number of deaths. However, Standardized Mortality Ratios, which account for shifting population distributions, have shown steadily decreasing values for both men and women since 1980. CONCLUSIONS: Recent improvements in cardiology care demonstrated in controlled clinical trials appear also to be present in epidemiological studies. PMID- 1617530 TI - Resuscitating the cardiology journal club. PMID- 1617531 TI - Microdialysis of noradrenaline in rostral ventrolateral medulla after intravenous methionine enkephalin administration in anesthetized rats. AB - The objective of this research was to define the role of central and peripheral opioid receptors for the regulation of cardiovascular action. Cardiovascular effects of methionine-enkephalin (met-enkephalin) after intracisternal, intravenous or direct administration into the rostral ventrolateral medulla (C1 area) were compared in inactin-anesthetized Sprague-Dawley rats. A microdialysis probe was stereotaxically implanted in the C1 area to dialyze monoamines during intravenous administration of met-enkephalin. An intravenous injection of met enkephalin decreased both arterial pressure and heart rate in a dose-dependent manner. There were no cardiovascular responses to intracisternal dosages of up to 10 micrograms/kg, but as little as 0.1 micrograms/kg met-enkephalin decreased arterial pressure and heart rate after a direct injection into the C1 area. Onset of the met-enkephalin effect was similar regardless of drug doses after intravenous administration; however, duration and magnitude of the peptide's action and time to peak effect were directly related to the dose. Intravenous infusion of 100 micrograms/kg/min met-enkephalin increased the extracellular concentration of noradrenaline in the C1 area. There was a differential blockade by naloxone of the hypotensive action of met-enkephalin after intravenous or C1 administration. This study suggests the importance of both central and peripheral sites(s) of met-enkephalin for its cardiovascular action. Additionally, the data suggest that the C1 area is a communication site between catecholamines and opioid peptides for cardiovascular regulation. PMID- 1617533 TI - Ultrasonography--whose turf? PMID- 1617532 TI - Preventing vascular injuries in revision total hip replacement. PMID- 1617534 TI - Aortobifemoral bypass--an enduring operation. AB - Aortobifemoral bypass (ABF) has been available as a method for treating patients with aortoiliac occlusive or aneurysmal disease for 40 years. ABF has been successful in alleviating the symptoms of claudication and critical ischemia. The long-term patency rates have been excellent with low operative morbidity and mortality. Major improvements have been made in indications, preoperative assessment and operative and postoperative care. With careful follow-up the natural history of a patient who undergoes ABF is known. Predicting outcome is now possible and a cost:benefit analysis can be made. ABF has proved to be a successful and enduring procedure. PMID- 1617535 TI - Arteritis due to Salmonella with aneurysm formation: two cases. AB - Although arterial infection due to Salmonella is rare, it remains one of the most common causes of primary mycotic aneurysms. The presentation is one of sepsis, cultures positive for Salmonella and rapid expansion or rupture of the aneurysm. The authors' experience at Victoria Hospital, London, Ont., includes two cases of aneurysms infected with Salmonella--one aneurysm of the aorta and the other of the common femoral artery. Both patients were treated by excision of the aneurysm, extra-anatomic reconstruction in an area remote from the infected field and long-term administration of appropriate antibiotics. One patient was alive and well 36 months after resection. The other died of multiple organ failure 10 days after resection. From a review of the English and French literature since 1948, 64 cases of abdominal aortic aneurysms infected with Salmonella were found; half of the patients survived the perioperative period. The diagnosis of mycotic aneurysm must be considered in any patient with an aneurysm and culture specimens positive for Salmonella. The authors favour wide debridement of the infected aneurysm with extra-anatomic reconstruction. This view is supported by a review of the literature. The appropriate antibiotic therapy is bactericidal rather than bacteriostatic. PMID- 1617536 TI - Vascular injury and repair associated with retroperitoneal lymphadenectomy for nonseminomatous germinal cell tumours of the testis. AB - Metastatic disease adjacent to major vascular structures in the retroperitoneum sometimes necessitates planned removal of portions of these vessels, or the vessels may inadvertently be injured when retroperitoneal lymphadenectomy is performed. In 78 patients who underwent retroperitoneal lymphadenectomy, 17 (22%) required vascular repair intraoperatively. The vena cava was most frequently involved (eight cases) followed by inadvertent injury to the renal arteries (five cases) or the infrarenal aorta (three cases). Resection of the infrarenal aorta was planned in two cases without postoperative complication. In six cases a resection of either the whole inferior vena cava or a portion of it was needed to remove all of the tumour. There were nine cases of inadvertent injury to the aorta, vena cava or a renal artery. The outcome after arterial repair was satisfactory with the exception of the inadvertent renal artery injuries, which required nephrectomy in three cases. Leg swelling was not a long-term sequela of either caval repair or resection. PMID- 1617537 TI - The role of descending venography in the management of patients with chronic venous disease of the lower extremity. AB - The purpose of this paper is to evaluate the efficacy and clinical information obtained from the authors' first 17 consecutive descending venograms. All 17 patients had chronic venous disease refractory to standard conservative and surgical measures. The standard classification of valvular insufficiency was used in evaluating these venograms. There were no deaths, slight morbidity and minimal patient discomfort. In 16 patients meaningful clinical information was derived from the venograms, with 7 patients having deep venous valvular surgery. Descending venography will demonstrate the site of incompetent valves and estimate the degree of reflux. This test is necessary before anticipated reconstruction of deep vein valves. PMID- 1617538 TI - Prevention of vascular injuries in revision total hip replacement. AB - Iliac-vessel injury from total hip arthroplasty is associated with hemorrhagic complications and an increased death rate. The authors identified seven patients who had severe medial displacement of the acetabular prosthesis and associated vascular injury to the iliac vessels after total hip replacement. One patient had two hip replacements. Preoperative findings included a pelvic mass (three hips), pelvic pain (eight), radiologic evidence of cement in the pelvis (three) and the acetabular prosthesis in the pelvis (eight), computed tomographic evidence of cement in the pelvis and proximity of the prosthesis to the iliac vessels (four), and arteriography showing displacement or compression of the iliac vessels (seven). Operative management in all cases involved medial exposure, mobilization and repair of the iliac vessels before revision of the hip prosthesis. Postoperative complications were deep vein thrombosis (three), in spite of prophylaxis, and occlusion of a vein interposition graft (one) requiring placement of a femoral crossover graft. There were no deaths, amputations or hemorrhagic complications. The authors advocate preoperative identification of patients who have iliac-vessel involvement by their total hip prosthesis and initial medial extraperitoneal exposure and repair of these vessels before removal of the displaced acetabular prosthesis. PMID- 1617540 TI - Scalp as a donor site for grafts to facial and neck burns in children. AB - In facial and neck burns, attention to cosmetic details, in addition to preservation of function, is crucial. The authors describe use of the scalp as a graft donor site for such burns. The advantages include excellent colour match of the graft and minimal morbidity at the donor site. The technique for graft harvest is outlined, and the potential pitfalls are described. Based on their experience with this technique, the authors believe the scalp should be considered as a donor graft site during the acute phase of facial and neck burns. PMID- 1617539 TI - Prosthetic replacement of the superior vena cava with a custom-made pericardial graft: an experimental study. AB - Prosthetic replacement of the vena cava has been disappointing, mainly because of the hemodynamic characteristics of the venous system and the physical properties of the prostheses used. Spiral grafts constructed with autogenous saphenous vein have been the most successful prostheses to date, but their use is limited to replacement of short segments, and intraoperative construction is time consuming. The authors report their experience with a graft constructed of extra-thick bovine pericardium (PX) and surgical staples. Externally stented polytetrafluoroethylene (PTFE) was used as a control. The superior vena cava was replaced in 13 ewes; PTFE was used in 6 (group 1) and PX in 7 (group 2). Mean follow-up was 15 +/- 8 months for group 1 and 13 +/- 8 for group 2. Cumulative graft follow-up totalled 4612 graft-days. There was one graft occlusion in each group. Patency rates (80%) were similar for the two groups. Histologic changes in pericardial grafts were more marked but did not influence patency. This study reports the longest experimental follow-up (maximum 23 months) and graft patency to date for replacement of the superior vena cava. Both types of graft performed excellently. PMID- 1617541 TI - Cemented ceramic acetabular component: a 7-year review. AB - A 7-year review of 30 cases of cemented ceramic acetabular components has shown that all components rapidly become surrounded by a lucent zone between the cement and bone that appears to be nonprogressive. Although these prostheses have functioned well, some separation inferiorly between the ceramic cup and the cement suggests that "creep" of the cup within the cement occurs and that the cup should be modified to provide greater "pull out" resistance from the cement. This study has failed to substantiate some of the theoretical advantages of ceramic cups. PMID- 1617542 TI - Priapism in the newborn. AB - The authors describe a rare case of priapism in a newborn infant. Treatment with intravenous ketamine hydrochloride produced rapid detumescence. The literature is reviewed with respect to priapism in the newborn and its management, and the authors propose injection of ketamine hydrochloride as an alternative method of management for this condition in newborn infants. PMID- 1617543 TI - An epidemic of hepatitis B among injection drug users in a rural area. AB - An epidemic of hepatitis B occurring in a rural area of Nova Scotia in 1988 and 1989 was investigated. This epidemic identified injection drug use (IDU) as the major determinant of transmission and was the first highly visible indication of IDU in rural Nova Scotia. Contact-tracing was used to identify 186 injection drug users (IDUs), of whom 153 (82%) were interviewed. Of 133 (72%) IDUs who underwent serological testing, 78 had serological evidence of hepatitis B infection. Using epidemiological criteria, 57 IDUs formed a cluster of hepatitis B infections. Using logistic regression techniques, age (O.R. = 1.1), the total number of IDU contacts named (O.R. = 1.1), and the number of hepatitis B seropositive IDU contacts named (O.R. = 1.3), were identified as risk factors predictive of an IDU being a cluster case. The characterization of this epidemic may be useful as a model for the spread of hepatitis B and other viral infections among IDUs in rural areas. PMID- 1617544 TI - Contact-tracing among injection drug users in a rural area. AB - An epidemic of hepatitis B occurring in 1988 and 1989 in Cape Breton brought to light the existence of a group of "buddies" who engaged in injection drug use. Interviewing was conducted by Public Health in 82% of the 186 IDU contacts named. In comparison with published reports of contact-tracing efforts for viral hepatitis among IDUs, the Cape Breton experience seems successful. This article describes the approach used by Public Health. Aspects of the management of the epidemic and the interview technique which may have contributed to the comparative success of contact-tracing include collaboration with family physicians and laboratories; collaboration among public health investigators; and a nonjudgemental interview technique with 6 "golden rules". PMID- 1617545 TI - Assessment of occupational health risk during unusual workshifts: review of the needs and solutions for modifying environmental and biological limit values for volatile organic solvents. AB - Aspects of occupational health risk assessment for unusual workshifts are discussed in relation to the question of: 1) using a suitable model for adjusting occupational exposure limits, and 2) assessing the influence of altered work schedules on biological exposure limits. The relative importance of two separate approaches, i.e., mathematical and pharmacokinetic, for the adjustment of exposure limits is discussed. Emphasis is placed on the usefulness of a physiologically based pharmacokinetic model for the exposure limits adjustments during prolonged work hours. The influence of prolonged work schedules on biological exposure limits is discussed and it is concluded that the latter do not have to be adjusted for unusual workshifts. Research needs arising as a result of unusual workshifts and pertaining to the practice of industrial hygiene and biological monitoring are suggested. PMID- 1617546 TI - [Strategies to increase and maintain high immunization levels in children]. AB - Various strategies for achieving high immunization rates and better knowledge of immunization status are evaluated. Sixty-nine studies were assessed. Laws requiring documented proof of immunity for all children at the beginning of the school year are associated with a substantial increase in immunization rates, while computerized registries contribute to improved knowledge of immunization status. Research on recall systems, whether parent or provider oriented, produces contradictory evidence. The question of provider motivation as a determinant for achieving high immunization rates remains to be adequately assessed. Laws requiring documented proof of immunity and access to a centralized and efficient immunization registry are key measures for maintaining high immunization levels. PMID- 1617547 TI - An investigation of two apparent cancer clusters in one community. AB - Two apparent cancer clusters in a single municipality were brought to public attention within a few years of each other. The clusters occurred first in a high school and later in a general hospital across the street. Analysis of the clusters was based on the comparison of the observed with the expected cancers, where the expectation of cancer occurrence was derived from data in the Ontario Cancer Registry. While the observed/expected ratios were statistically significant for the high school staff and students, these ratios were based on a very small number of cases (n = 6), and represented 4 different cancer types. The data for the hospital did not appear as excess cancer, either across age groups or in different working locations within the hospital. In addition, cancer rates were examined for the town in which the high school and hospital were located. A number of alternative explanations are discussed, as are the issues surrounding the analysis of cancer clusters in the community. We concluded that the two apparent clusters did not require further study. PMID- 1617548 TI - A study to validate the Canadian Aerobic Fitness Test. AB - Our purpose was to assess the validity of VO2 max values predicted from The Canadian Aerobic Fitness Test (CAFT) by comparing them with peak VO2 values measured during a maximal treadmill protocol. Male and female subjects, 15-69 yr (n = 129), performed two submaximal exercise tests (CAFT protocol), and one maximal treadmill test. There was no significant heart rate habituation between the first two CAFT protocols. Peak VO2 values measured during the treadmill test (TM) were significantly higher than those predicted from the CAFT whether the sample was analyzed overall or categorized by sex. When the sample was categorized by age group, all but groups 1 (15-19) and 6 (60-69) had treadmill peak VO2 values significantly higher than those predicted using Jette's equation. Using treadmill measured peak VO2 scores as the gold standard, VO2 max predictions using the CAFT protocol and Jette equation placed individuals of lower fitness levels more accurately than highly fit individuals, into one of five fitness categories. PMID- 1617549 TI - Meningococcal disease and public health: welcome to the '90s. PMID- 1617550 TI - The Prince Edward Island meningococcal immunization program. January-February 1992. PMID- 1617551 TI - [Mass vaccination against meningococcal disease in three regions of the province of Quebec, January 1992]. PMID- 1617552 TI - An outbreak of meningococcal disease in Ottawa-Carleton. December 1991-February 1992. PMID- 1617553 TI - Meningococcus meningitis in Ottawa, 1940-41. PMID- 1617555 TI - Meningococcal disease and death in rural Alberta. December 1991. PMID- 1617554 TI - Invasive meningococcal disease, British Columbia. December 1991-March 1992. PMID- 1617556 TI - Incidence and prevalence of end-stage renal disease among Ontario's James Bay Cree. AB - End-stage renal disease (ESRD) and chronic renal failure (CRF) among Canadian natives is more common than among the general Canadian population. The results of this study show the James Bay Cree in Northern Ontario in 1989 experienced ESRD prevalence rates 3.2 times greater than the national rate. The average annual incidence rates for 1981-1989 were 1.6 times the national rate. Methodological difficulties inherent in incidence and prevalence studies of native Canadians are examined. With tertiary treatment care facilities available only in southern urban centres, native Canadians in remote northern communities face considerable psychosocial disruption when seeking out medical assistance for ESRD such as renal dialysis services. PMID- 1617557 TI - Needs of the family caregivers of frail elderly. AB - The purpose of the study was to determine the needs of family caregivers of frail elderly. Forty-one caregivers were interviewed. More than two-thirds of the caregivers were spouses and about 85% of them had health problems which affected their caregiving. Ninety-eight percent of the caregivers were living with the care recipients and the cumulative stress from their continual involvement had affected their lifestyle. Also more than 58% felt that the care recipients needed more care than they could provide. More than 68% of the caregivers were seniors. Differential planning based on each of the caregivers' needs can maximize the care they provide. PMID- 1617558 TI - Income inequalities in oral health among older adults in four Ontario communities. AB - We used data from telephone interviews, personal interviews and clinical examinations to assess income inequalities in oral health among older adults living in four Ontario communities. Lower income groups had significantly higher rates of edentulism than upper income groups. In dentate subjects aged 50 to 64 years, significant associations were observed between income and 9 of 10 clinical, functional and subjective oral health indicators. Among those aged 65 years and over, associations were found for only 5 of these indicators. The data suggested that the association between income and clinical and functional measures of oral health was stronger among those aged 50 to 64 years, while the association between income and subjective indicators was stronger among those aged 65 years and over. No association was noted between income and oral health status among edentulous subjects. These observations are difficult to explain because of the cross-sectional nature of the study and the complexity of the processes which may lead to social inequalities in health. Nevertheless, the data do suggest the need for the targeting of oral health promotion programs and appropriate dental services at disadvantaged groups. PMID- 1617559 TI - Factors associated with acquiring giardiasis in British Columbia residents. AB - Giardia is the most frequently reported intestinal parasite in Canada. More than 2,000 cases are reported annually in British Columbia which exceeds the number of cases of either campylobacteriosis or salmonellosis. Since the different ways this parasite is spread in British Columbia have not been determined, our purpose was to investigate certain factors that might be associated with acquiring giardiasis in this province. Telephone interviews provided information from a group of infected persons and from a group of non-infected control subjects. Information obtained from these interviews was used to identify associated risk factors in this group of cases. If results of the study are generalized to the population-at-risk, they indicate that water (drinking and recreational) is an important vector for transmission of Giardia in British Columbia. PMID- 1617560 TI - Health promotion and health advocacy for and by immigrants enrolled in English as a second language classes. AB - An intersectoral immigrant health promotion project in Hamilton, Ontario is described. The project goal was to facilitate the entry of new immigrants to the Ontario health care system and equip them with knowledge and skills to strengthen their preventive and promotive health practices. A needs assessment preceded project development. The three phases of the project are described. The first phase commenced with the development of culturally sensitive health promotion resource materials to be used with immigrants enrolled in English as a Second Language Classes. In phase two, activities focussed on strengthening the ability of ESL teachers to incorporate a preventive and promotive health focus in their classes. The final phase shifted to a community-based project. During this phase, a core immigrant group developed their skills as health advocates for their immigrant community. PMID- 1617561 TI - Health of Canada's aboriginal people. PMID- 1617562 TI - Chaos and public health: implications for an epidemic. PMID- 1617563 TI - Perceived health status and desired health information needs of university students. PMID- 1617564 TI - Changing profiles of a typology of youth suicide in Canada. PMID- 1617565 TI - The effectiveness of commercially available disinfectants upon Giardia lamblia cysts. PMID- 1617566 TI - Fluoridation: a prophylaxis program for dental caries and dementia? PMID- 1617568 TI - Baby Susan. PMID- 1617567 TI - Aluminum, fluoride and the prevention of Alzheimer's disease. AB - The evidence regarding the link between aluminum and Alzheimer's disease is summarized. This evidence suggests strongly that aluminum is one of the etiologic or contributing factors in the occurrence of Alzheimer's disease. One reported study suggests that relatively high fluoride in drinking water plays a preventive role in Alzheimer's disease. The rationale for this is the evidence that aluminum and fluoride compete for absorption in the gut. However, this study had methodologic limitations, and no firm conclusion can be drawn. Further investigation of relatively high fluoride in drinking water as a preventive measure for Alzheimer's disease should receive high priority. PMID- 1617569 TI - Resolving the health care crisis: where is the CNS? PMID- 1617570 TI - The clinical nurse specialist as case manager in a collaborative practice model: bridging the gap between quality and cost of care. AB - The status of the current health care environment demands that health care providers deliver quality health care while reducing health care costs. While the nursing profession is faced with the critical issue of providing quality cost effective care, the clinical nurse specialist (CNS) is caught in a controversy created by cost containment efforts and the nursing shortage. To provide effective yet efficient care mandates that patient care be comprehensive and integrated. This article presents a model of delivery of care that proposes the utilization of the CNS in a collaborative model of practice based upon case management. The operationalization of the model is based upon the interweaving of the role dimensions of the CNS, the goals of case management, and the components of collaborative practice into patient care. PMID- 1617571 TI - The CNS as a cost manager. AB - The role of the clinical nurse specialist (CNS) in a cost-conscious environment includes the need to be alert to opportunities for cost-containment. Efforts to improve the quality of nursing care need to be balanced with the ability to manage costs. The CNS is in a key position to guide and influence decision-making about cost savings. This article reviews costs in health care and the elements of total nursing costs. CNSs can affect costs in three areas: direct costs, indirect costs, and supplies/equipment. Practical examples in each of the three areas are given for actions that are potentially useful to the CNS who desires to reduce the costs to patients and document the cost savings generated by nursing. PMID- 1617573 TI - Family and group psychoeducational approaches in the management of schizophrenia. AB - The family movement is one of the most important movements in the mental health field in recent decades. In light of this trend, a psychoeducational focused group for schizophrenics and their families to learn management of schizophrenic illness is described. Antipsychotic medication for patients is assured by depot administration by the facilitator in a clinic immediately after the group sessions. This psychoeducational approach can serve as a prototype for others. PMID- 1617572 TI - Let's talk about clinical consultation. PMID- 1617574 TI - The clinical nurse specialist as expert witness. AB - A clinical nurse specialist is an ideal expert witness in cases alleging nursing negligence. Nurses choose to serve in this capacity for a variety of reasons. As an expert witness, a clinical nurse specialist may act as a consultant, review medical records, give depositions, translate medical jargon, testify in court, educate attorneys, suggest questions for attorneys to ask of witnesses, and provide opinions about the standard of care a client received. Guidelines for qualifications of an expert, reviewing medical records, preparing opinions, and testifying are given. Reactions to serving as an expert are discussed. PMID- 1617575 TI - Pessimism or optimism for role recognition? PMID- 1617576 TI - Music therapy: an intervention to reduce anxiety in the myocardial infarction patient. AB - The purpose of this study was to examine the effects of relaxing music on elevated state anxiety in patients with a confirmed medical diagnosis of acute myocardial infarction. In addition, the relationship between trait anxiety and state anxiety was analyzed. A purposive sample of 40 myocardial infarction patients was randomly assigned to an experimental or control group. Statistically significant reduction in heart rate, respiratory rate, and state anxiety scores were found in the group that listened to relaxing music. A statistically significant positive correlation was found between trait anxiety scores and baseline state anxiety scores. Statistically significant negative correlations were found between trait anxiety scores and the degree of change in posttreatment state anxiety scores when examined as a net change, as well as a percent change. Results suggested that music therapy may be an effective intervention to reduce state anxiety levels in the acute myocardial infarction patient. PMID- 1617577 TI - Case management and the CNS. PMID- 1617578 TI - Case management of homeless families. AB - Homeless families are the fastest growing subgroup of the homeless population. They have multiple health care needs that can be best met by the community clinical nurse specialist. Nursing actions must be planned based on an assessment of this group's unique service needs. Interventions require the use of individualized delivery strategies such as case management, which necessitates that the clinical nurse specialist develop specialized skills in both service stimulation and system advocacy. PMID- 1617579 TI - The clinical nurse specialist in the school setting: case management of migrant children with dental disease. AB - Dental disease is a major health problem for all school-age children in the nation; for migrant children the problem is most severe. This paper presents strategies for the clinical nurse specialist (CNS) in the school setting in case management of migrant children with dental disease. The barriers migrant families face in obtaining health care are addressed. Leininger's transcultural care theory serves as a conceptual framework. Examples of how the CNS functions in the roles of clinician, educator, consultant, and researcher are given. The federally funded Migrant Education Program is described, along with a model dental program developed by a CNS. Suggestions for documenting the effectiveness of the CNS's role in cost containment and in influencing positive outcome measures of school age children are presented. PMID- 1617580 TI - Regression analysis. PMID- 1617581 TI - "The role of pediatric clinical nurse specialist in a general emergency department". PMID- 1617582 TI - Application of the case study design: nursing interventions for discharge readiness. AB - A single case study design was used to explore the nursing process and intervention related to discharge preparation of one family with a child requiring complex care at home. Helping methods described by Orem were used to categorize identified nursing interventions. Discharge readiness was assessed to verify consideration of conditions for discharge. The major study question was "How is discharge preparation conducted?" Collected data provided evidence to support each of three case study propositions: (1) patients and their home caregivers are involved in discharge preparation as planners and as learners, (2) nursing interventions occur in five major helping areas as outlined by Orem, (3) discharge preparation addresses each component of discharge readiness. The case study design was effective as an approach to explore nursing interventions, verify considerations of discharge conditions, and refine the concept of discharge readiness. A decision trail is presented for nurses to replicate the process with questions related to their practice. PMID- 1617583 TI - A content methodology for advancing gerontological nursing practice. AB - The content methodology process is a method of observation, research, and application that refines the caregiving practice. An application of the content methodology process with cognitively-impaired individuals with dementia is explored, and correlations drawn to language abilities of older patients. PMID- 1617584 TI - Determining CNS cost effectiveness. PMID- 1617585 TI - Live in the past ... or face the future??? PMID- 1617586 TI - Definition of an advanced nursing practice role in the NICU: the clinical nurse specialist/neonatal practitioner. AB - We surveyed 655 health professionals affiliated with tertiary level neonatal intensive care units in Canada and the United States to define an expanded role for nurses in neonatology and to determine the educational requirements for the role. The role, comprising advanced clinical practice, educational, research, and administrative responsibilities, is a blend of nurse practitioner and clinical nurse specialist activities. Based on survey findings, a neonatal stream within the existing Master of Health Sciences program at McMaster University was developed. To date, 15 clinical nurse specialists/neonatal practitioners (CNS/NPs) are employed in five neonatal intensive care units in Ontario and other related institutions. A randomized trial to evaluate these individuals is in progress. PMID- 1617587 TI - A nursing bioethics program. AB - In 1985 the Seattle Veterans' Administration Medical Center nursing service implemented a nursing program for bioethics with three goals: (1) to expand the nurse's knowledge of bioethical principles, (2) to develop the nurse's ability and confidence in analyzing bioethical dilemmas, and (3) to increase bioethical application at the bedside. Two psychosocial clinical nurse specialists (CNSs) led this highly successful nursing program that prepared nurses to more actively and responsibly participate in bioethical decision making within the medical center. The program offers an annual workshop for new members, holds a monthly discussion group, conducts a yearly enrichment program, and completes an annual evaluation report. This article describes nursing service bioethics program from planning through evaluation and the role of the CNS as program coordinator, facilitator, and educator in the expanding field of bioethics. PMID- 1617588 TI - The World Health Organization's Histological Classification of Salivary Gland Tumors. A commentary on the second edition. AB - The second edition of the World Health Organization's Histological Classification of Salivary Gland Tumors is more extensive and detailed than the previous edition published 20 years ago. The new edition is based on data regarding newly described tumor entities and the behavior and prognosis of the previously classified tumors. The distinct morphologic features of monomorphic adenomas justify their separation for purposes of identification. Among the carcinomas, various types were distinguished for purposes of recognition, prognosis, and treatment. The term tumor was replaced by carcinoma in the following two entities: acinic cell carcinoma and mucoepidermoid carcinoma. The tumor-like lesions were described in more detail. PMID- 1617589 TI - Prophylactic lymph node dissection in patients with advanced gastric cancer promotes increased survival time. AB - BACKGROUND: There is no consensus of opinion regarding the efficacy of lymph node dissection. METHODS: Data were analyzed from 452 patients with advanced gastric cancer who underwent curative resection in the Department of Surgery II, Kyushu University Hospital, between 1970 and 1985, with special reference to the lymph node metastasis. RESULTS: Metastatic lesions were evident in the dissected lymph nodes of 300 of 452 (66.4%) patients. Survival time for patients without lymph node metastasis was longer than for those with it (P less than 0.01). In patients without lymph node metastasis, the tumor was smaller, serosal invasion was less prominent, tumor growth was less infiltrating, and the tumor stage was, therefore, less advanced. Lymphatic involvement was found in 38.9% of the patients with no evidence of lymph node metastasis. CONCLUSIONS: Because the postoperative mortality rate is low in patients with lymph node dissection, the authors advocate prophylactic lymph node dissection to prevent a recurrence. PMID- 1617590 TI - Social class and colon cancer survival in Finland. AB - METHODS. Social class differences in colon cancer survival were studied in 3147 patients with colon cancer diagnosed in Finland from 1979-1982. Of these patients, 2969 were eligible for survival analysis. RESULTS. A clear social class gradient in colon cancer survival was detected. The difference in the age adjusted relative risk of death due to colon cancer between the highest (I) and lowest (IV) social class was 19%. Stage of disease at diagnosis accounted for a substantial proportion of differences in survival, and treatment accounted for the rest of them. Differences in treatment by social class were most apparent among patients with advanced or unknown stage of disease at diagnosis. Controlling for the place of residence had little effect on the survival differences. Delay in diagnosis did not account for the observed differences in survival by social class. PMID- 1617591 TI - The WHO Histological Classification of Tumors of the Gallbladder and Extrahepatic Bile Ducts. A commentary on the second edition. AB - The second edition of the WHO Histological Classification of Tumors of the Gallbladder and Extrahepatic Bile Ducts is more comprehensive and detailed than the previous one. Advances in our understanding of dysplasia, carcinoma in situ, various lines of differentiation among the carcinomas, and the recognition of a variety of tumor-like lesions have resulted in more than three times as many entities in the current classification as in the previous one. The new edition should facilitate pathologic, epidemiologic, and therapeutic comparisons. PMID- 1617592 TI - Lung cancer in association with human immunodeficiency virus infection. AB - The association of lung cancer and infection by the human immunodeficiency virus (HIV) is uncommon. This report and critical review of the medical literature defines a clinical profile of 22 patients affected with this uncommon association. This clinical profile includes young age (median, 38 years), intravenous drug abuse (14 of 22 patients), preponderance of adenocarcinoma over other cell subtypes (11 of 22 patients), and advanced clinical stage at presentation (10 of 15 patients with staging data had Stage III or IV disease). This study also examines a possible increased risk for lung cancer in patients infected by HIV. Continued surveillance and reporting of lung tumors (other than lymphomas and Kaposi sarcomas) in patients infected by HIV should help to define the frequency of the association and the validity of the clinical profile. PMID- 1617593 TI - Cardiac metastasis of lung cancer. A study of metastatic pathways and clinical manifestations. AB - BACKGROUND: Although lung cancer frequently spreads to the heart, details of cardiac metastases of lung cancer have not been fully discussed. The authors attempted to elucidate the relationship between the mechanisms of cardiac metastasis and a variety of clinical manifestations caused by cardiac metastasis. METHODS: Clinical and autopsy records were reviewed in 74 autopsied cases of lung cancer. In cases with cardiac metastasis, the metastatic pathways to the heart were determined by the macroscopic examinations, and the relationship between the metastatic pathways and the clinical manifestations were studied. RESULTS: Metastases to the pericardium or heart were seen in 23 cases (31%). A lymphatic metastatic pathway was detected in 18 cases (hilar lymphatic routing in 12 cases, and mediastinal lymphatic routing in 6 cases), and a hematogenous metastatic pathway was detected in 5 cases. Malignant pericardial effusion was documented in 15 of 23 cases. The metastatic pathway in 14 of 15 cases was lymphatic (hilar lymphatic routing in 10 cases, and mediastinal lymphatic routing in 4 cases). Patients showing lymphatic metastasis had higher incidence of malignant pericardial effusion than those with hematogenous metastasis (P less than 0.05). Of 23 cases of cardiac metastasis, myocardial infarction was found in 1 case, resulting from the compression of the coronary arteries by the tumor. Concurrent supraventricular arrhythmias were recorded in eight cases with cardiac metastasis. Patients with cardiac metastasis had higher incidence of arrhythmia than those without cardiac metastasis (P less than 0.05). In cases of cardiac metastasis, patients with arrhythmia were older (P less than 0.01) than those without arrhythmia. CONCLUSIONS: The authors concluded that the hilar lymphatic pathway is essential for early development of malignant pericardial effusion in lung cancer and that aging and cardiac metastasis may be responsible for arrhythmia in patients with lung cancer. PMID- 1617594 TI - Malignant thymoma. AB - Sixty-one patients underwent operations for malignant thymomas between 1961 and 1989. Twenty-three patients had associated myasthenia gravis (MG), an incidence of 37.7%. Upon being admitted to the hospital, the patients' most common symptoms included chest pain, MG, cough, and dyspnea. Only 7 of 61 (11.5%) patients had no symptom. Tumor staging of 58 patients with invasive thymomas was performed according to Masaoka classification. The patients were classified as follows: Stage II disease, 5; Stage III, 41; Stage IVa, 8; and Stage IVb, 4. In addition, thymic carcinoma was present in three patients. The series had a resection rate of 55.7%. The incidence of operative complications was 16.3%. Only one patient died of myocardial infarction; the incidence of operative mortality was 1.6%. The patients with MG had a higher rate of resection (69.6%) and a higher incidence of complete thymectomy (14 of 23 patients; 60.9%). Mixed lymphoepithelial tumors and epithelial cell predominant tumors were the most frequent histologic patterns (45.9% and 34.4%, respectively). Fifty-two patients had postoperative radiation therapy, and 10 patients had chemotherapy. The overall cumulative survival rates in the series were 59% and 34% at 5 and 10 years, respectively. The results demonstrated that the factors affecting the prognosis may include resectability, postoperative irradiation or chemotherapy, MG, and tumor staging. The influence of histologic variation on survival rates could not be clearly defined in the series. Surgical resection, particularly complete thymectomy, followed by irradiation is the primary option of therapeutic management for malignant thymoma. PMID- 1617595 TI - Spleen findings in generalized mastocytosis. A clinicopathologic study. AB - BACKGROUND: Little information regarding the morphologic findings of the spleen in generalized mastocytosis (GM) is available and no comprehensive review of the literature on this subject has been published. METHODS: The authors reviewed their records to study the macroscopic and microscopic features of the spleen in 53 patients; the authors also studied these features in 135 patients reported in the literature. Thus, a total of 188 patients with GM were studied. RESULTS: Splenomegaly was noted in 72% of the patients, including 71% of the patients from the authors' files and 73% of the patients reported in the literature. The spleen weight, recorded in 39 of the patients, ranged from 160 g to 2300 g; in 29 (80%) patients the spleen weighed more than 500 g and in 4 (10%) patients, more than 2000 g. However, mast cell (MC) infiltration of the spleen was recorded in only 65 (34%) patients (patients from authors' records, 39%; patients reported in literature, 32%). The following combinations were extremely rare: splenomegaly without evidence of MC infiltration (n = 1); and histologic evidence of MC infiltration in the absence of splenomegaly (n = 2). The histologic findings of the spleen could be assessed in nine of the patients from the authors' files, eight of whom had MC infiltration. In four patients, infiltration was diffuse and confined mainly to the red pulp; in the other four patients, it was more focal and involved mainly the white pulp. Spleen plasmacytosis was found in eight patients, eosinophilia in five, hemosiderosis in seven, and fibrosis in six. Concurrent acute nonlymphoblastic leukemia was diagnosed in four patients, none of whom had the skin lesions of urticaria pigmentosa. CONCLUSIONS: The authors' findings show that (1) splenomegaly is a common finding in GM and often is pronounced; (2) MC infiltration probably is the most important factor in the pathogenesis of splenomegaly in this disease; and (3) two different patterns of MC infiltration (diffuse and focal) can be identified in GM. PMID- 1617596 TI - Bone resorption by macrophage polykaryons of a pilar tumor of scalp. AB - The nature of keratin-associated giant cells of a pilar tumor of scalp (PTS) was assessed for several osteoclast-like characteristics, including antigenic phenotype, ultrastructure, calcitonin response, and bone resorbing ability. The giant cells, unlike osteoclasts, did not respond morphologically to calcitonin, had the antigenic phenotype of cells of the monocyte/macrophage lineage, and showed ultrastructural features of macrophage polykaryons. However, like osteoclasts, the giant cells were capable of bone resorption, including resorption pit formation. This indicates that the giant cells in PTS are of histiocytic and not osteoclastic differentiation. Bone resorption by tumor associated macrophage polykaryons shows that this is not a unique defining characteristic of osteoclasts. It also suggests that such histiocytic cells may contribute to the osteolysis associated with skeletal metastases of squamous and other carcinomas. PMID- 1617597 TI - Recurrent cutaneous leiomyosarcoma. AB - BACKGROUND: Soft tissue sarcomas comprise approximately 0.7% of all malignant neoplasms. Superficial leiomyosarcoma, a rare malignant lesion, constitutes 4.0 6.5% of all soft tissue sarcomas, an overall incidence of approximately 0.04% among all cancers. Currently, less than 125 cumulative cases of cutaneous and subcutaneous leiomyosarcoma have been reported in the English literature. METHODS: The authors report the case of a 70-year-old Japanese man with recurrent cutaneous leiomyosarcoma who was treated by wide local excision. A comprehensive literature survey is also presented. RESULTS: The patient is free from recurrence 1 year after wide local excision of a second recurrence of cutaneous leiomyosarcoma. Moreover, superficial leiomyosarcoma can be subdivided into cutaneous leiomyosarcoma and subcutaneous leiomyosarcoma, based on histopathologic and prognostic differences. CONCLUSIONS: The treatment of choice of superficial leiomyosarcoma is wide local excision. Cutaneous leiomyosarcoma is associated with local recurrence only, although subcutaneous leiomyosarcoma undergoes metastatic spread in 30-60% of cases, with a 30-40% mortality rate. PMID- 1617598 TI - Detection of local recurrence after conservative therapy for breast carcinoma. AB - BACKGROUND: Early detection of local recurrence after conservative therapy for breast cancer is associated with improved survival. This review was undertaken to determine the ability to detect recurrence and identify patterns of recurrence. METHODS: Records of women with local tumor recurrence were retrospectively reviewed. RESULTS: In 42 women with 43 local recurrences, tumors were detected by mammography alone in 18 instances (42%), physical examination alone in 14 (33%), and by both in 11 (25%). Of 29 recurrences mammographically detected, 19 were diagnosed by microcalcifications, 9 by a mass, and 1 by a mass with microcalcifications. Twenty of 25 tumors detected by physical examination were felt as a mass. Recurrences detected by mammography were more often in situ (72% or 13 of 18) than those detected by physical examination alone (7% or 1 of 14). Treatment failure at the site of the original tumor seemed to occur earlier than failures elsewhere in the breast and was more common in women younger than 43 years of age or with disease that was originally axillary node-positive. CONCLUSIONS: Mammography often detects more in situ recurrences than physical examination, but both are complimentary. Recurrence at the site of the original tumor is usually earlier and in younger women and may be associated with tumors that were originally node-positive. PMID- 1617599 TI - Independent validation of APACHE II severity of illness score for predicting mortality in patients with breast cancer admitted to the intensive care unit. AB - BACKGROUND: To determine the validity and predictive accuracy of the Acute Physiology and Chronic Health Evaluation (APACHE II) scoring system for severity of illness by comparing the actual hospital mortality with the predicted mortality for patients with breast cancer admitted to the intensive care unit (ICU). METHODS: APACHE II scores were calculated based on retrospective evaluation of the medical records of 52 patients with breast cancer who received ICU care. The relationships between hospital mortality and APACHE II scores, number of sites of metastatic disease, duration of metastatic disease, number of chemotherapeutic regimens given for metastatic disease, presence of neutropenia or thrombocytopenia, age, reason for ICU admission, and length of ICU stay were assessed. RESULTS: Twenty-two patients (42%) died during the hospital stay during in which they were admitted to the ICU. Predicted mortality based on a logistic regression model using APACHE II scores was 21 patients (40%). APACHE II specificity was 87%; sensitivity was 54%. There were significant relationships between presence of metastatic disease, number of metastatic sites, reason for ICU admission, and length of ICU stay. Patients with more than two sites of metastatic disease and those with respiratory failure had particularly poor chances of survival. Regression analysis incorporating the number of sites of metastatic disease, reason for ICU admission (whether for a pulmonary or a cardiovascular problem), and APACHE II score suggested that APACHE II could predict hospital survival. CONCLUSIONS: This retrospective study showed that APACHE II scores were associated with hospital mortality in patients with breast cancer who were admitted to ICU. The number of metastatic sites and the type of major organ system failure were also associated with outcome. Regression analysis suggested that APACHE II scores were independently associated with survival outcome. PMID- 1617600 TI - Breast carcinoma presenting as axillary metastases without evidence of a primary tumor. AB - BACKGROUND: Sixty cases of axillary metastases from clinically occult breast cancer were analyzed. All cases had histologic evidence of metastatic nodes compatible with breast carcinoma. METHODS: Thirty-three patients underwent breast surgery at the time of histologic diagnosis of the axillary metastases, 6 patients were treated with radiation therapy to the breast, and 17 patients did not receive any immediate treatment of the breast carcinoma (9 of these subsequently had a primary breast carcinoma) during the follow-up. Thirty-seven of 60 patients underwent adjuvant therapy (29 underwent chemotherapy and 8 underwent tamoxifen therapy). From the histologic point of view, the number of metastatic nodes was 1 in 13 patients, 2 to 3 in 10 patients, and 4 or more in 23 patients; the number of metastatic nodes was not evaluable in 14 cases. Invasion was extranodal in 92% of cases. Eighty-six percent of cases were histologically classified as Grade 3 according to Bloom and Richardson. RESULTS: The 5-year and 10-year survival rates were 77% and 58%, respectively. The comparison between the survival curves of the patients treated with immediate surgery/radiation therapy and of the patients whose cases were followed-up without treatment to the breast showed no difference. Adjuvant treatments did not improve prognoses. CONCLUSIONS: The coexistence of a minimal (or unidentifiable) primary carcinoma with an extensive involvement of axillary nodes and a predominance of the undifferentiated histologic type, together with an unexpectedly good prognosis, makes this type of presentation an interesting example of a dissociated host resistance. PMID- 1617601 TI - Mammography screening credit card and compliance. AB - BACKGROUND: Screening for breast cancer using mammography has been shown to be effective in reducing mortality from breast cancer. The authors attempted to determine if use of a wallet-size plastic screening "credit" card would increase participants' compliance for subsequent mammograms when compared with traditional methods of increasing compliance. METHODS: Two hundred and twenty consecutive women, ages 40-70 years, undergoing their first screening mammography were recruited and assigned randomly to four groups receiving (1) a reminder plastic credit card (2) reminder credit card with written reminder; (3) appointment card; and (4) verbal recommendation. Return rates of the four groups were determined after 15 months. RESULTS: The return rate for subsequent mammograms was significantly higher for participants (72.4%) using the credit card than for participants (39.8%) exposed to traditional encouragement/reminders (P less than 0.0001). CONCLUSIONS: The credit card was designed to show the participant's screening anniversary, and the durability of the card may have been a factor in increasing the return rate. The use of reminder credit cards may increase compliance for periodic screening examinations for other cancers and other chronic diseases. PMID- 1617602 TI - Functioning ovarian carcinoids induce severe constipation. AB - Five patients with ovarian carcinoid who had severe constipation for a long period preoperatively showed marked reduction of this symptom postoperatively. Because this phenomenon was believed to be caused by some biologically active substance rather than a mechanical effect of the tumor, reactivity to 17 amine and peptide hormones was studied immunohistochemically in these patients. Numerous peptide YY (PYY)-positive cells were detected, with PYY-positive cells representing more than 50% of all carcinoid tumor cells in each patient. PYY, which has a pharmacologic inhibitory action on intestinal motility, was presumably the cause of the constipation in these patients. PMID- 1617603 TI - Cerebral neurocytoma. A new subset of benign neuronal tumors of the cerebrum. AB - Three cases of patients with unusual neuronal tumors in the cerebral hemisphere are reported. All were associated with long-standing epileptic seizures. Computed tomography disclosed low-density lesions without contrast enhancement, which were interpreted as either arachnoid cysts or a cerebral infarction at initial diagnosis. Magnetic resonance imaging scans, however, revealed the lesions to be solid tumors. At surgery, the tumors were found to be relatively well demarcated, soft, and gelatinous. Histologically, all tumors were composed of small uniform stellate cells, which proliferated in a loose myxoid fibrillary matrix and resembled either oligodendroglial or astrocytic tumors. Ultrastructurally, however, all tumors showed neuronal differentiation, including numerous clear and occasional dense-core vesicles, microtubules, and a number of synapses. A review of the literature uncovered no other such cases, and therefore it was decided to classify these tumors as a distinct group of benign neuronal tumors, designated as "cerebral" neurocytoma compared with "intraventricular" neurocytoma. Related nosologic problems of neuronal tumors of the central nervous system and their possible histogenesis are also discussed. PMID- 1617604 TI - Precursor Langerhans cell histiocytosis. An unusual histiocytic proliferation in a patient with persistent non-Hodgkin lymphoma and terminal acute monocytic leukemia. AB - BACKGROUND: Langerhans cell precursors are considered to be identical to their mature counterparts except for the lack of Birbeck granules. Proliferations composed of such histiocytes appear to be uncommon. METHODS: Standard immunophenotypic, molecular genetic, and DNA content studies were used to characterize various hematopoietic disorders, including a proliferation of precursor Langerhans cells, which arose sequentially in a patient. RESULTS: The patient studied initially had a low-grade, B-cell, non-Hodgkin lymphoma and subsequently had an unusual histiocytic proliferation (precursor Langerhans cell histiocytosis) in cutaneous and lymph node sites. The patient eventually died of acute myelogenous leukemia (FAB, M5). CONCLUSIONS: A larger series is required to determine the significance of the precursor Langerhans cell phenotype, particularly with respect to the development of acute myelogenous leukemia. PMID- 1617605 TI - Necrotizing pneumonitis caused by 5-fluorouracil infusion. A complication of a Hickman catheter. AB - The authors report the case of a patient with a Hickman catheter that migrated into the lung parenchyma. The resultant inadvertent infusion of 5-fluorouracil caused necrotizing chemical pneumonitis. Possible mechanisms of catheter migration include the lateral orientation of the catheter tip and the partial thrombosis of the innominate vein and superior vena cava. The patient recovered but had residual contraction fibrosis of the right upper lobe of the lung. PMID- 1617606 TI - Diagnostic value of microvillus-matrix associations in tumors. AB - Until now microvillus-matrix associations have been reported to occur only in mesotheliomas and hence this phenomenon is thought to be of value in distinguishing mesothelioma from pulmonary adenocarcinoma. We report here the occurrence of microvillus-matrix associations in two pulmonary adenocarcinomas which reduces the value of this phenomenon in the differential diagnosis of these tumors. PMID- 1617607 TI - New interpretations in rhinosporidiosis, enigmatic disease of the last nine decades. AB - Fungal etiology is widely quoted for the disease rhinosporidiosis. Identity of the fungal sporangium and its relationship with the disease have baffled medical scientists and mycologists for several decades. This study provides unequivocal evidence against involvement of fungus in rhinosporidiosis. The so-called sporangium is found to be a unique body containing residue-loaded lysosomal bodies ('spores') for elimination from the system. 'Sporangia' have been redesignated nodular bodies (NB) and 'spores' as spheres of cellular waste (scw). Two carbohydrates, namely defective proteoglycans synthesized intracellularly and an exogenous polysaccharide ingested through diet of tapioca constitute indigestible material in NB and scw. Polysaccharide in NB which has beta, 1-4 glycosidic bonds between mannose residues is not degraded by gastrointestinal enzymes nor in intracellular lysosomes which break only alpha-glycosidic bonds. A link between NB and dry tapioca has been deduced. Rhinosporidiosis is a complex phenotype with perhaps no parallel in medical science. This report erases 99 years (1892-1991) of controversies regarding 'causal organism' of rhinosporidiosis. PMID- 1617608 TI - Morphometric analysis of Mauthner axon cytoskeletal components in adult and subadult fish. AB - A previous cytoskeletal analysis on trout MA during developmental stages demonstrated, during the subadult stages, neurofilaments (NF) as main components as expressed by the high values of neurofilament to microtubules (MT) ratio which was found to be of the order of 300:1. Since the MA cytoskeletal composition is not known in the adult fish, the MA cytoskeletal composition has been compared to other axons of much smaller diameter of the fasciculus longitudinalis medialis (flm) among which the MA run in the ventral spinal cord. The following parameters were measured on conventional electron microscopy in MA and flm axons cross sections micrographs by means of a computer linked graphic tablet (Apple II): axonal caliber, number of microtubules (MT), microtubular (MT/microns2) and neurofilament (NF/microns2) densities. The analysis of these parameters demonstrated that neurofilaments are the main architectural components in the adult and subadult fish MA and flm axons. However, MA cytoskeletal composition differs from the other flm axons because of its particular very high ratio of neurofilaments to microtubules. The inverse relationship of axonal caliber to microtubular density, previously found in the trout during developmental stages and suggested also for many other vertebrate species, was further confirmed for flm axons which, with calibers 10 times smaller than MA, exhibit a microtubular density 10 times larger. PMID- 1617609 TI - The axonal microtubular density is higher than normal in fibres innervating spastic muscles. AB - In infants with spastic disorders and with congenital dysplasia of the hip (CDH), the microtubular content of nonmedullated and myelinated fibres of the anterior obturator nerves was studied with the electron microscope. In CDH infants, the microtubular content of nonmedullated and myelinated fibres was similar to values reported for experimental animals. In spastic patients, the microtubular content of nonmedullated fibres was similar to that found in CDH patients while the microtubular densities of 3- and 10-microns myelinated fibres were 37.5 and 16.7 microtubules/micron2, respectively, or 100% and 43% greater than corresponding values of CDH patients. We propose that the high firing rate determines the abnormally high microtubular content of myelinated axons supplying spastic muscles. PMID- 1617610 TI - Unusual assembly juxtaposed to Golgi elements in a mitotic B16F10 mouse melanoma cell. PMID- 1617611 TI - Preferential localization of hafnium in nodular lymphatic cells. Study by electron microprobe. AB - In a previous work we used the electron microprobe to study the intracellular localization of zirconium after administration of soluble salt at low doses. That element was concentrated in nodular lymphatic cells. In the present work using the same methods we studied hafnium, another element in group IVb of the periodic table, which has chemical properties similar to zirconium. After administration at low doses of soluble salt of hafnium, this element was similarly concentrated in nodular lymphatic cells and was as zirconium uniquely localized in the lysosomes of macrophages where it is associated with phosphorus. PMID- 1617612 TI - Met-enkephalin induces fast synaptic plasticity of magnocellular neurons in the rat supraoptic nucleus. AB - A morphometric-ultrastructural study was made of the supraoptic nucleus of rats of both sexes following central administration of met-enkephalin. Ten minutes after met-enkephalin treatment the number of axo-somatic synapses was significantly increased. This effect was more pronounced in female rats than in males and could be prevented by preceding administration of naloxone. Animals that received naloxone followed by met-enkephalin showed a dilation of the rough endoplasmic reticulum into a vesicular shape. Our results provide preliminary evidence for a fast remodeling of synaptic input to magnocellular hypothalamic neurons. It is likely that the known inhibitory action of opioids on the hypothalamo-neurohypophysial system is partly mediated by this plasticity. PMID- 1617613 TI - Influence of a short oxidative stress on the LDL endocytosis by human endothelial cells: an ultrastructural study. AB - Following injury induced by oxidant stress (exposure to xanthine-xanthine oxidase during 120 min), cultured human umbilical vein endothelial cells were severely modified. These lesions were evaluated by electron microscopy and the types of injury were shown to be progressive cell blebbing as well as altered mitochondrial features. Enlargement of the endoplasmic reticulum and swelling of the Golgi apparatus were also observed. With the intention of learning more about the role of oxygen-derivative-induced alterations of the endocytotic apparatus (plasma membrane, endosomes, lysosomes), the receptor-mediated endocytosis of colloidal gold-conjugated LDL was evaluated. It was demonstrated that this endocytosis is drastically decreased following this type of injury, corroborating our previous report of important reduction in 125I-LDL endocytosis under the same conditions. Tubular electron-lucent structures, often observed in the vicinity of blebs, could possibly be involved in the impairment of LDL receptor accessibility. PMID- 1617614 TI - Tight endothelial junctions in the developing microvasculature: a thin section and freeze-fracture study in the chick embryo optic tectum. AB - The development of the interendothelial tight junctions was studied in the microvessels of the otpic tectum of chick embryos, at the 14th-16th and 18th-20th incubation day (i.d.), and in post-hatching chickens, using thin sections and freeze-fracture techniques. At the 14th-16th i.d., the junctional plasmamembranes of the endothelial cells are simply apposed or fused for brief tracts showing a pentalaminar or trilaminar configuration. In the replicas the P-faces of the fractured junctional membranes are either lacking in intramembrane particles (IMPs) and characterized by finger-like depressions, or provided with discrete IMPs aligned in rows. At the 18th-20th i.d., the thin peripheral expansions of the endothelial cells are superimposed and welded by continuous pentalaminar junctions. Their fracture P-faces display junctional strands formed by parallel fibrils of fused IMPs, with or without interconnections. In the 10-day-old chickens the junctions consist of highly complex networks of fibrils. The results have made it possible to recognize precise relationships between the features of the developing endothelial junctions in the ultrathin sections and, respectively, in the replicas. Moreover, the observations suggest that tight junction formation occurs progressively in the cerebral microvessels by processes of alignment and fusion of the IMPs, which conclude with the arrangement of fibrils in networks. PMID- 1617616 TI - Instruments that measure beliefs about cancer from a cultural perspective. AB - Understanding beliefs about cancer from a cultural perspective is of great importance as the population mix of this country continues to shift and change. In order to assess the cancer beliefs held by diverse populations, culturally specific tools are needed. The purpose of this article is to identify and describe instruments that have been used to assess beliefs about cancer. Eight published and unpublished instruments were identified from a review of the literature. These tools address attitudes and beliefs toward cancer, cancer prevention, and cancer treatment within a variety of age groups and ethnic populations. One tool was related to adolescents, whereas the remainder focused on adults; three were translated into other languages; four tools involved questionnaire format and four interview format. Although it is encouraging to report that culturally specific tools are being developed, there is a demonstrated need to increase the expertise in developing such instruments. PMID- 1617615 TI - Blood vessel architecture in lymph nodes of the dog viewed by scanning electron microscopy. AB - Scanning electron microscopy was used to investigate the submicroscopic organization of the blood vessels of dog lymph nodes (LN). The LN vessels were casted by systemic perfusion of the animals vasculature with two resins of distinct viscosity. This resulted in the retrieval of two types of LN vascular replicas that depicted either the arterial blood system alone (methacrylate casting) or both the arterial and venous blood systems (Mercox casting). We found that the dog LN showed a significantly higher density of arterial vessels in the cortex than in the medulla. In the cortical domain, a subcapsular layer stood out because of its rich content in arterial capillaries. The use of the high resolution resin (mercox) resulted in excellent structural detail of the luminal surface of the LN vessels that allowed a clear distinction between arterioles and venules based on the geometrical pattern of the imprints left in the replicas by the nuclei of endothelial cells. At the cortex-medulla frontier, most arterioles showed narrowings of their lumen that suggested the existence of sphincters at this level. Our findings document that the microanatomical arrangement of blood vessels in the LN of the dog is different from that of LN from other mammals studied so far, in particular from rodents where vascular-poor microdomains have been reported in the LN cortex. The arteriolar sphincters that we detected at the innermost zone of the cortex may represent the structural counterpart of the physiological modulation of the blood supply of the cortex exerted by arterial branches coming from the hilus. PMID- 1617617 TI - Potential predictors of information-seeking behavior by homosexual/bisexual (gay) men with a human immunodeficiency virus seropositive health status. AB - Seeking ways to improve their health, gay men with human immunodeficiency virus (HIV) infections living in San Francisco are developing information networks and patterns of self-care behavior. Drawing from a set of explanatory theories, this cross-sectional survey with retrospective elements examined patterns and potential predictors of information-seeking activity in a cohort or 162 HIV seropositive (HIV+) men, 60 of whom provided complete data sets. The study suggests that 1 year after becoming aware of an HIV+ health status, most patients have developed multifaceted information networks. The amount of tangible aid acquired from these networks and frequency of consultation is positively related to patterns of HIV self-care behaviors and "feeling calm" (p less than 0.01), suggesting that these variables may be important markers for the need of supportive-educative nursing care. Suggestions for nursing practice and research are also described. PMID- 1617618 TI - Bereavement care. A role for nurses. AB - Bereavement care is an important, yet often forgotten, area of care. Evidence suggests that early and prompt interventions for high-risk individuals can facilitate grief and can minimize the adverse consequences of grief. Nurses can play a pivotal role in providing care to bereaved individuals. However, it is essential to have a thorough knowledge of the normal grief response, and a framework for assessment and management. This article provides fundamental information about the manifestations of grief, and offers information about appropriate nursing assessment and management for bereaved individuals. PMID- 1617619 TI - Use of ethyl chloride topical anesthetic to reduce procedural pain in pediatric oncology patients. AB - Pediatric cancer patients often become anxious, agitated, combative, and uncooperative due to the pain or fear of pain during invasive procedures. Generally, it is not the actual administration of medicines that produces this reaction, but the fear of the needle stick itself. Increased education and implementation of coping mechanisms is often not enough to allay this fear. The tangible solution of using ethyl chloride, an anesthetic spray, before port sticks, lumbar punctures, and bone marrow aspirations, was instituted by the hematology-oncology clinic to determine if the pain, emotional trauma, and fear of cancer treatments could be reduced in oncology patients. Survey results on 60 patients and 60 parents/caretakers showed that when given the choice to use the spray or to refuse its use, 68% of the parents thought that the patient had more of a sense of control and, thus, involvement in their treatment. Seventy-eight percent of the patients reported experiencing less pain associated with procedures. Staff noted an increase in cooperation, less combativeness, and more compliance with treatment. Perceiving the child's discomfort diminished, 87% of the parents/caretakers report feeling less anxious and, therefore, more capable of being supportive to each other and their child. These results verified the staff's perceptions of the advantages of using this noninvasive anesthetic. Ethyl chloride is an easy, effective, concrete approach to reducing procedural pain in pediatric oncology patients. PMID- 1617620 TI - Fundamentals for a new concept of oncology nursing in the professional nursing education program. AB - Cancer is a life-threatening illness affecting approximately one-third of the population in America and western Europe. All nurses and student nurses will in all probability be confronted at some time in their careers with the specific problems of cancer patients and their families. Are all nurses, however, being prepared in their basic nursing education programs to deal with these problems? It is the purpose of this paper, first of all, to examine this question through a review of appropriate literature and through review of a questionnaire, sent to nursing students in their final semester, relating to perceived needs in this area. Secondly, our purpose is to suggest actions that may need to be taken in order to assure quality care of cancer patients and adequate preparation and support of professional nurses involved in this care. PMID- 1617621 TI - Nursing's involvement in the primary and secondary prevention of cancer. Nationally and internationally. PMID- 1617622 TI - Inhibition of dihydroorotate dehydrogenase activity by brequinar sodium. AB - The novel anticancer drug candidate brequinar sodium (DuP 785, NSC 368390, 6 fluoro-2-(2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl-4-quinoline- carboxylic acid sodium salt) was shown previously to be an inhibitor of dihydroorotate dehydrogenase, the fourth enzyme of the de novo pyrimidine biosynthetic pathway. Brequinar sodium inhibits the activity of this enzyme isolated from mammalian sources only but not those forms isolated from yeast or bacteria, which also use ubiquinone as the cofactor. Brequinar sodium also does not inhibit the activity of a soluble Zymobacterium oroticum dihydroorotate dehydrogenase which uses NAD+ as a cofactor. Brequinar sodium inhibits L1210 dihydroorotate dehydrogenase with mixed inhibition kinetics with respect to either the substrate (dihydroorotate) or the cofactor (ubiquinone Q6) with Ki' values in the 5-8 nM range. Our results suggest that brequinar sodium inhibits dihydroorotate dehydrogenase by binding to the enzyme at a unique site that is distinct from the dihydroorotate or the ubiquinone-binding site. This binding site appears to be unique to the mammalian enzyme, because brequinar sodium does not inhibit the yeast, Escherichia coli, or Z. oroticum forms of the enzyme. PMID- 1617623 TI - Uptake of the noncytotoxic transport probe procainamide in the Chinese hamster ovary model of multidrug resistance. AB - Many of the cytotoxic substrates of the multidrug transporter are organic cations. Cimetidine, procainamide, and tetraethylammonium bromide were used in a Chinese hamster ovary model of multidrug resistance, to study handling of noncytotoxic cationic transport probes. Cimetidine and procainamide, but not tetraethylammonium, accumulated to a greater extent (5-fold) in the sensitive CHOAUXB1 (AB) cell line than in the resistant CHRC5 (C5) cell line. Accumulation of both cimetidine and procainamide was significantly increased by verapamil in C5 but not AB. Procainamide accumulation in both AB and C5 was temperature dependent and occurred by passive diffusion. Diltiazem, nifedipine, rifampin, tamoxifen, rhodamine, and ethidium also increased procainamide accumulation in C5 but not AB. Azide in glucose-free medium increased procainamide accumulation in C5, and this was reversed when glucose, but not 3-O-methylglucose, was added. Procainamide efflux rates were similar in AB and C5 and not affected by verapamil or azide. The initial rate of procainamide uptake was higher in AB than in C5, and both verapamil and azide increased the initial rate of procainamide uptake in C5. Thus, differences in accumulation of the noncytotoxic transport probe procainamide in the colchicine-sensitive and colchicine-resistant components of the Chinese hamster ovary cell line mimic the accumulation of known cytotoxic substrates for the multidrug transporter, such as colchicine, vinblastine, and doxorubicin. The differential accumulation of procainamide is due to differences in rates of drug influx, rather than efflux. Since procainamide influx is passive and decreased accumulation in the resistant line appears to parallel M(r) 170,000 glycoprotein presence and activity, we would speculate that decreased procainamide accumulation may be due to an indirect effect of the M(r) 170,000 glycoprotein, such as its effect on intracellular pH. PMID- 1617624 TI - Metabolism of N-nitrosomethyl-n-amylamine by microsomes from human and rat esophagus. AB - Asymmetric dialkylnitrosamines induce esophageal cancer in rats and hence might be involved in the etiology of this cancer in humans. As a test of this hypothesis, we examined whether nitrosamines can be activated by segments of human esophagus and by microsomes of human and rat esophagus and liver. Specimens of 8 human esophagi were removed less than 6 h after death, and segments were incubated for 6 h with 23 and 300 microM N-nitrosomethyl-n-amylamine (NMAA). Hydroxy-NMAA yields were determined by gas chromatography-thermal energy analysis and were insignificant except for those of 5-hydroxy-NMAA, which were low. Microsomes were prepared from 4 batches of human esophagi and samples with 0.6 mg protein were incubated for 20 min with NMAA and cytochrome P-450 cofactors. We determined hydroxy-NMAAs as before and aldehydes by high-performance liquid chromatography of their 2,4-dinitrophenylhydrazones. Incubation of these microsomes with 12 mM NMAA yielded mean values of 0.64 nmol formaldehyde ("demethylation"), 0.21 nmol pentaldehyde ("depentylation"), and 0.56 nmol total hydroxy-NMAAs/min/mg protein. Metabolite yields under various conditions were determined, including a demonstration that carbon monoxide inhibited 81% of NMAA demethylation, indicating that cytochrome P-450 enzymes were involved. We also examined N-nitrosodimethylamine (NDMA) demethylation by the same microsomes. Rat esophageal microsomes dealkylated NMAA and NDMA similarly to human esophageal microsomes, but with 2-6 times and twice the activity, respectively. Human and rat esophageal microsomes demethylated 6 mM NMAA 18-20 times as rapidly as they demethylated 5 mM NDMA, in contrast to liver microsomes of these species, which demethylated 6 mM NMAA only 0.9-1.4 times as rapidly as they demethylated 5 mM NDMA. However, liver microsomes of both species were more active than esophageal microsomes for NMAA depentylation. The occurrence of NMAA demethylation and (to a lesser extent) depentylation with both human and rat esophageal microsomes is important because these are the activating reactions, and suggests that both human and rat esophagus contain P-450 isozymes that specifically dealkylate asymmetric dialkylnitrosamines. PMID- 1617625 TI - Synergism between dipyridamole and cisplatin in human ovarian carcinoma cells in vitro. AB - Dipyridamole (DPM), a nucleoside membrane transport inhibitor, enhanced the cytotoxicity of cisplatin (DDP) for human ovarian carcinoma 2008 cells by a factor of 4.7 +/- 0.4-fold (mean +/- SD) and for the 10-fold DDP-resistant 2008/C13*5.25 subline by a factor of 5.8 +/- 2.7-fold. This interaction was shown to be truly synergistic by isobologram and median effect analysis. DPM enhancement of DDP cytotoxicity was schedule dependent; it was greatest when cells were exposed to DPM continuously during and following a 1-h exposure to DDP and less pronounced when DPM exposure was limited to pretreatment or concurrent treatment only. DPM increased DDP uptake in a concentration-dependent manner as measured with both [195mPt]-DDP and the DDP analogue [3H]-cis dichloro(ethylenediamine) platinum. Nitrobenzylthioinosine, another nucleoside membrane transport inhibitor, did not enhance DDP cytotoxicity or uptake at concentrations that produced equivalent degrees of inhibition of [3H]uridine uptake. DPM did not interact synergistically through an increase in cellular cyclic AMP levels. DPM did not increase trypan blue or propidium iodide uptake, or change cell size, indicating that it did not nonspecifically increase membrane permeability. We conclude that DPM interacts synergistically with DDP and that, while an increase in DDP uptake is one component of the mechanism of this interaction, there are additional components since maximal effect was observed only with prolonged DDP exposure. PMID- 1617627 TI - Acrolein initiates rat urinary bladder carcinogenesis. AB - Acrolein, a reactive, alpha,beta-unsaturated aldehyde which is ubiquitous in the environment, forms DNA adducts, is mutagenic, and is teratogenic. However, studies have not indicated a carcinogenic effect in rodent bioassays. Since it is present in cigarette smoke and is the toxic metabolite of cyclophosphamide with respect to the urinary tract, we investigated the possibility that acrolein might have carcinogenic activity toward the rat urinary bladder. We also evaluated whether it possessed initiating and/or promoting activity. To evaluate initiating activity, acrolein was administered at a dose of 2 mg/kg i.p. twice a week for 6 weeks followed by uracil as 3% of the diet for 20 weeks and then control diet for 6 weeks. N-[4-(5-Nitro-2-furyl)-2-thiazolyl]formamide (FANFT) as 0.2% of the diet followed by uracil was used as a positive control, and a negative control group was administered solvent control (water) i.p. during the 6-week initiation period followed by uracil. Acrolein followed by uracil produced an incidence of 18 of 30 rats (60%) with papilloma compared to 8 of 30 rats (27%) treated with solvent control followed by uracil. FANFT followed by uracil produced an incidence of 70% carcinomas and 30% papillomas, clearly indicating that it is a much more potent initiating agent than acrolein. Acrolein for 6 weeks followed by control diet produced no tumors. To evaluate promoting activity, groups of rats were fed FANFT for 6 weeks followed by acrolein. Acrolein administered during the initial 6 weeks and continued for the second phase of the experiment (to evaluate complete carcinogenic activity) resulted in severe toxicity. Administration of acrolein had to be terminated after 21 weeks of the experiment. The animals were maintained for 53 weeks of the experiment without further chemical treatment, and there was no evidence of papilloma or carcinoma development. This study clearly indicates that acrolein has initiating activity for the urinary bladder when administered by i.p. injection to the male F344 rat, but toxicity precluded evaluation of its promoting or complete carcinogenic activity. PMID- 1617626 TI - Adriamycin-induced modulation of host defenses in tumor-bearing mice. AB - Using the C57BL/6/EL4 tumor model, studies were carried out to demonstrate the feasibility of administering Adriamycin (ADM) in therapeutic doses and schedules such that the host antitumor defenses would not be suppressed and in some cases might be stimulated by treatment. ADM treatment caused prolongation of survival and, in general, either stimulated host cytolytic activities above untreated control levels or had no effect. These effects by ADM were observed with the ADM sensitive parent EL4 line as well as with an ADM-resistant subline, indicating that the effects did not result entirely from direct antitumor activity. The cytolytic activities examined were those of cytolytic T-lymphocytes, lymphokine activated killer cells, and splenic and peritoneal macrophages. All activities were assessed against the syngeneic EL4 target line. The information obtained in this investigation provides a rational basis for the future development of curative protocols with ADM plus biological response modifiers, which would depend on a functional immune system for optimum efficacy and would also exploit synergistic immunomodulating effects of the agents used in combination. PMID- 1617628 TI - Inhibition of skin tumor promoter-caused induction of epidermal ornithine decarboxylase in SENCAR mice by polyphenolic fraction isolated from green tea and its individual epicatechin derivatives. AB - Green tea, next to water, is the most popular and commonly consumed beverage in the world, especially in eastern countries. In prior studies we have shown that the polyphenolic fraction isolated from green tea (GTP) exerts antigenotoxic effects in various mutagenicity test systems (Mutat. Res., 223: 273-285, 1989) and that its topical application or oral feeding in drinking water protects against polycyclic aromatic hydrocarbon-induced skin tumor initiation and complete carcinogenesis in SENCAR and BALB/c mice [Cancer Lett., 42: 7-12, 1988; Carcinogenesis (Lond.), 10: 411-415, 1989] and UV B radiation-induced photocarcinogenesis in SKH-1 hairless mice [Carcinogenesis (Lond.), 12: 1527 1530, 1991]. In the present study we assessed the effect of skin application of GTP to SENCAR mice on 12-O-tetradecanoylphorbol-13-acetate (TPA) and other skin tumor promoter-caused induction of epidermal ornithine decarboxylase (ODC) activity. Topical application of GTP to mouse skin inhibited TPA-induced epidermal ODC activity in a dose-dependent manner. The inhibitory effect of GTP was also dependent on the time of its application relative to TPA treatment. Maximum inhibitory effect was observed when GTP was applied 30 min prior to topical application of TPA. GTP application to animals also inhibited the induction of epidermal ODC activity caused by several structurally different mouse skin tumor promoters. In order to identify which of the specific epicatechin derivatives present in GTP is responsible for these inhibitory effects, they were isolated from GTP and evaluated for their inhibitory effects against TPA-caused induction of epidermal ODC activity. Among these, ( )epigallocatechin-3-gallate (EGCG), which was the major constituent present in GTP by weight, exerted the maximum inhibition. EGCG also showed greater inhibitory effects against TPA-caused induction of epidermal ODC activity when compared with several other naturally occurring polyphenols. The results of this study suggest that GTP, specifically its epicatechin derivative EGCG, could provide anti-tumor-promoting effects against a wide spectrum of skin tumor promoters. PMID- 1617629 TI - Meal frequency and risk of colorectal cancer. AB - The relation between meal frequency and the risk of colorectal cancer was investigated in a case-control study conducted in North Italy on 889 cases of colon cancer, 581 cases of rectal cancer, and 2475 controls admitted to hospital for acute, nonneoplastic, or digestive disorders. As compared to individuals who reported 2 or fewer meals per day, the multivariate colon cancer odds ratios were 1.7 [95% confidence interval (95% CI), 1.5-2.1] for 3, and 1.9 (95% CI, 1.1-3.3) for 4 meals or more. Corresponding rectal cancer odds ratios were 1.4 (95% CI, 1.1-1.7) for 3, and 1.9 (95% CI, 1.1-3.5) for 4 meals or more. The direct trends in risk of colorectal cancer with frequency of eating were not substantially modified by allowance for various dietary and nondietary potential confounding factors, including an approximate measure of total energy intake, and did not show significant effect modification across strata of age, sex, education, and other major risk covariates. A role of meal frequency in the etiology of colorectal cancer is biologically plausible, since when a meal is eaten, the gallbladder contracts and releases bile acids. Thus, eating patterns can influence the enterohepatic circulation and, consequently, the exposure time of intestinal mucosa to bile acids. PMID- 1617630 TI - Interaction of antileukemia agents adriamycin and daunomycin with sphinganine on the differentiation of human leukemia cell line HL-60. AB - A slight induction of granulocytic differentiation of HL-60 cells occurred after treatment with antileukemia chemotherapeutic agents Adriamycin (ADM) and daunomycin (DM). Addition of an inhibitor (sphinganine, SP) of protein kinase C (PKC) enhanced 2-4-fold the ADM or DM-induced differentiation. This phenomenon was accompanied by a slightly augmented antiproliferative effect. The enhancement of differentiation induction in these treatments seemed to be absolute, since the combination treatment (ADM-SP or DM-SP) showed about 2.5-3.6 times as many differentiated cells as the treatment with the anticancer drugs ADM or DM alone. Further characterization of the interaction of ADM and DM with SP on differentiation of HL-60 cells was carried out. Whereas the addition of SP in the fresh medium after the removal of ADM or DM (0.5 h treatment) enhanced the induction of differentiation, a pretreatment (24 h) of the cells with SP followed by continuous exposure to ADM or DM did not show such enhancement effect. The addition of SP at as late as 48 h after the administration of ADM or DM potentiated the induction of differentiation to the same extent as in the simultaneous combination of ADM-SP or DM-SP. Similar results were obtained in the experiments with another PKC inhibitor, staurosporine. These results indicated that inhibition of PKC activities may play an important role in the later events during the induction of differentiation elicited by ADM or DM. The use of the antileukemia drugs ADM and DM in combination with an inhibition of PKC activity results in enhancement of induction of differentiation and suggests a new strategy and a promising approach to the treatment of leukemia. PMID- 1617631 TI - L-histidinol: preclinical therapeutic studies in combination with antitumor agents and pharmacokinetic studies in mice. AB - Therapeutic studies were conducted with L-histidinol, in combination with cyclophosphamide, bischloroethylnitrosourea, 5-fluorouracil, phenylalanine mustard, or cis-platinum(II)diammine dichloride, in several transplantable tumors in mice. These tumor types included murine L1210 P388 leukemias, M5076 sarcoma, mammary 16/C adenocarcinoma, human LOX melanoma, and colon HT-29 adenocarcinoma. Therapeutic benefits of adding L-histidinol to a regimen, compared to the regimen alone, were marginal. Pharmacokinetic studies indicated a rapid clearance of L histidinol following a bolus dose (250 mg/kg i.p.), peak plasma concentration of 200 micrograms/ml (1.4 mM), and beta phase t1/2 of 12.6 min. Maximum tolerable plasma steady state concentrations with a 24-h infusion (2000 mg/kg/24 h) were no greater than 25 micrograms/ml (0.18 mM). PMID- 1617632 TI - Inhibition of in vitro ovarian cancer cell invasion by modulation of urokinase type plasminogen activator and cathepsin B. AB - HOC-I ovarian cancer cells express the single-chain form of the urokinase-type plasminogen activator (uPA) and cathepsin B (cath B) on their cell surface. The significance of the expression of cell surface uPA/cath B activity to the invasive potential was examined by preincubating with uPA/cath B-modulating agents in in vitro invasion assay. The anti-uPA monoclonal antibody 394 effectively inhibited invasion in a dose-dependent manner. On the contrary, anti cath B antibody did not affect the invasive potential of the cells. E-64, a specific inhibitor for cysteine proteases, blocked invasion as effectively as monoclonal antibody 394. The data reveal that the uPA and cysteine proteases contribute significantly to the invasive capacity of the cells. We suggest that the cysteine proteases facilitate the action of uPA, possibly by activating proenzyme uPA produced by cancer cells. Evidence for the role of a cathepsin-uPA activation cascade in HOC-I cell invasion is provided. PMID- 1617633 TI - 2-Amino-3,4-dimethylimidazo[4,5-f]quinoline induces and inhibits cytochrome P450 from the IA subfamily in chick and rat hepatocytes. AB - Several heterocyclic amines, found in cooked food, are powerful mutagens in the Ames Salmonella mutagenicity test system. One of these, 2-amino-3,4 dimethylimidazo[4,5-f]quinoline (MeIQ) is one of the most mutagenic chemicals tested in this assay. In primary cultures of chick and rat hepatocytes, MeIQ, by itself, induced cytochrome P450 from the IA subfamily but was a weak inducer compared to 3-methylcholanthrene. However, in both chick and rat hepatocytes in culture, MeIQ decreased the amount of 3-methylcholanthrene-induced ethoxyresorufin deethylase activity, which is catalyzed by cytochrome P450 IA. The protein moiety of cytochrome P450 IA was decreased at MeIQ concentrations of 2.5 micrograms/ml or greater in chick hepatocytes and 25 micrograms/ml in rat hepatocytes. In hepatic microsomes from methylcholanthrene-treated chicks and rats, MeIQ was a competitive inhibitor of both ethoxyresorufin deethylase activity, a reaction catalyzed mainly by rodent cytochrome P450 IA1, and uroporphyrinogen oxidation, a reaction catalyzed by rodent P450 IA2. In cultured chick hepatocytes, MeIQ also decreased cytochrome P450-mediated oxidation of uroporphyrinogen by intact cells. The ability of MeIQ to inhibit as well as to induce cytochrome P450s of the IA subfamily may be important in assessing the mutagenic and carcinogenic effects of MeIQ in mammals. PMID- 1617634 TI - Characterization and purification of a guanidinobenzoatase: a possible marker of human renal carcinoma. AB - Guanidinobenzoatases are cell surface-associated proteinases supposed to be involved in cancer metastasis, cell migration, and tissue remodeling. The main features of the guanidinobenzoatase associated with human renal carcinoma plasma membrane are weak membrane association, continuous cleavage of p-nitrophenyl-p' guanidinobenzoate conversely to the site titration effect of this compound when used with trypsin, and a peculiar sensitivity to serine protease inhibitors, compatible with a poorly active form. Plasma membrane preparation followed by agmatine-trisacryl affinity chromatography allows the purification of guanidinobenzoatase to homogeneity with an apparent enrichment factor of 450. Purified guanidinobenzoatase appears as a single polypeptide chain of M(r) 80,000, likely stabilized by intrachain disulfides bonds. The properties of purified guanidinobenzoatase indicate that it is an original enzyme in spite of some similarities with plasminogen activators. Indeed, in addition to differences in substrate and inhibitor specificity, guanidinobenzoatase is not recognized by specific monoclonal antibodies directed against plasminogen activators or their single-chain precursors. Thus, human renal carcinoma guanidinobenzoatase appears to be an original enzyme whose activity is undetectable in the nontumoral tissue of origin. In this respect, use of purified guanidinobenzoatase would allow us to obtain specific tools to give new insights in cancer cell metastasis. PMID- 1617635 TI - Low-density lipoprotein for delivery of an acrylophenone antineoplastic molecule into malignant cells. AB - In vitro and in vivo data have indicated that tumor cells actively internalize the low-density lipoprotein (LDL) from the circulation. A family of 2 (aminomethyl) acrylophenones (AMA) possesses an in vitro antileukemic activity but is devoid of any in vivo antineoplastic activity, because the compounds are actively captured by proteins in solution in the blood. In order to achieve a selective delivery of these drugs via the LDL pathway, we have incorporated an AMA drug, 2-morpholinomethyl-2',3',4'- trimethoxy acrylophenone hydrochloride (ILE) into LDL particles. ILE spontaneously associated with LDL to produce an LDL ILE complex containing 200 +/- 100 molecules of drug per LDL particle. The LDL ILE complex was highly electronegative as detected by electrophoresis. Further, this complex presented an immunologically detected over expression of the ligand binding domain to the LDL receptor. In spite of these modifications, the LDL receptor processing bound, internalized, and degraded the LDL-ILE complex. Nevertheless, these biological properties were reduced by 32, 20, and 40%, respectively, in comparison to native LDL. Despite its high electronegativity, the LDL-ILE complex was not recognized by the macrophagic scavenger receptor. The LDL-ILE complex showed specific LDL receptor mediated in vitro cytotoxicity as judged from the growth inhibition of neoplastic A549 cells and of normal fibroblasts, but no activity on defective LDL receptor cells. Further, the pharmacological activity of the complex against A549 cells has been demonstrated to be equally potent as that of the free drug (median inhibitory dose, 5 microM). It is suggested that LDL drug targeting of AMA molecules could specifically deliver active molecules to cancer cells, avoiding their entrapment by other blood proteins and their rapid clearance by the reticuloendothelial system. PMID- 1617636 TI - Inhibition of breast cancer cell growth in vitro by a tyrosine kinase inhibitor. AB - Human breast cancer cell proliferation is regulated by growth factors that bind to receptors with intrinsic tyrosine kinase (TK) activity, including the epidermal growth factor (EGF) receptor. To determine whether inhibition of receptor TK activity inhibits tumor growth, we studied the effects of a tyrosine kinase inhibitor, RG-13022, on cultured human breast cancer cells. RG-13022 represents a class of compounds which have been shown to inhibit preferentially the TK activity of the EGF receptor in a cell-free system and also to inhibit EGF stimulated growth of cultured cells. RG-13022 significantly inhibited EGF stimulated autophosphorylation of its receptor in two breast cancer cell lines that have abundant, although not amplified, EGF receptor content (MDA-231 and T47D). RG-13022 also inhibited EGF-stimulated DNA synthesis and proliferation of T47D and MCF-7 breast cancer cells in a reversible and dose-dependent manner. Inhibition was observed at 0.1 microM, and it was maximal at 10 microM. The effect was rapid (within 3 h), persisted for 18 h, and was partially reversed by 24 h at 1 microM. At 5 microM, inhibition persisted for more than 50 h. Inhibitory effects were also observed in a panel of estrogen receptor-positive and estrogen receptor-negative breast cancer cell lines. RG-13022 inhibited not only EGF-induced growth but also growth stimulated by insulin, insulin-like growth factor I, insulin-like growth factor II, or transforming growth factor alpha. RG-13022 also totally blocked estrogen-stimulated phosphorylation of the EGF receptor, as well as estrogen-induced cell proliferation, suggesting that functioning TK pathways are required for estrogen action. The TK inhibitor RG 13022 is a potent inhibitor of hormonally regulated growth of human breast cancer. Tyrosine kinase inhibitors have the potential of providing a new strategy for the "endocrine therapy" of breast cancer. PMID- 1617637 TI - New approach for detection of amplification in cancer DNA using restriction landmark genomic scanning. AB - We developed a new approach for detecting the gene amplification of cancer DNAs with restriction landmark genomic scanning (RLGS). In cancer research, much effort has been made to find the amplified loci of cancer DNAs, because many lines of evidence indicate association between oncogene amplification and carcinogenesis. Conventionally, such gene amplification has been detected by using Southern hybridization with DNA probes. However, only the information of one locus can be obtained by one hybridization procedure, and analysis of many loci throughout the genome is too laborious and time consuming, even if only several candidate genes are investigated. On the other hand, the "in-gel renaturation method" was reported as another alternative for detection of amplified regions. However, even though this method is much improved, it is difficult to detect less than 7-fold amplification, which is often higher than the amplification of many cancer cases. To overcome these limitations and, in addition, to locate the amplified DNA two dimensionally, we applied RLGS for analysis of DNA amplification in cancer tissues, such as breast cancer (infiltrative tubuloadenocarcinoma), neuroblastoma, meningioma (endotheliomatous meningioma), and thyroid cancer (papillary adenocarcinoma). In some cases of breast cancer, several amplified spots located on the same amplicon were detected. In thyroid cancer, in which no amplification has yet been reported, low grade amplification was also detected. In this report, we demonstrated that RLGS allows us to screen 2000-3000 restriction landmarks distributed on the genome simultaneously, and even low-grade amplification could be detected effectively. Thus, RLGS has proven to be a very useful method in detecting DNA amplification. PMID- 1617638 TI - Response of human breast cancer cells to heat shock and chemotherapeutic drugs. AB - Previous studies have shown that certain chemotherapeutic drugs are less effective on tumor cells when cells have been previously exposed to hyperthermia. In the present study, we have evaluated whether specific modifications in heat shock protein (hsp) expression are associated with resistance to anticancer drugs. RNA levels for hsp90, hsp70, and hsp27 were studied by Northern and slot blots, while proteins were studied by two-dimensional gel electrophoresis, in MCF 7/BK and MDA-MB-231 breast cancer cells. The sensitivities of these cells to doxorubicin, colchicine, 5-fluorouracil, cisplatin, actinomycin D, and methotrexate were tested by clonogenic assays. These techniques were applied to both cell lines before (control) and after heat shock. The study revealed that elevated hsp70 and hsp27 levels were associated with doxorubicin resistance. In addition, the presence of phosphorylated hsp27 isoforms was also associated with doxorubicin resistance. The study showed that elevated hsps were not associated with multidrug resistance. Heat shock did not induce P170 glycoprotein mRNA overexpression or resistance to the other drugs tested. We also found that the level of doxorubicin protection conferred by the overexpression of hsp was lower than that obtained in cells expressing a multidrug resistance phenotype (MDA-A1R cells). In these cells, heat shock did not confer additional doxorubicin resistance and hsp27 phosphorylation was deficient. Our studies suggest that specific hsps are associated with doxorubicin resistance in certain human breast cancer cells and that this mechanism seems to be independent of the multidrug resistance system. PMID- 1617639 TI - Effect of a dihydropyridine analogue, 2-[benzyl(phenyl)amino]ethyl 1,4-dihydro 2,6-dimethyl-5-(5,5-dimethyl-2-oxo- 1,3,2-dioxaphosphorinan-2-yl)-1-(2 morpholinoethyl)-4-(3-nitrophenyl)-3 -pyridinecarboxylate on reversing in vivo resistance of tumor cells to adriamycin. AB - A newly synthesized dihydropyridine analogue, 2-[benzyl(phenyl)-amino]ethyl 1,4 dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorina n-2-yl)-1- (2 morpholinoethyl)-4-(3-nitrophenyl)-3-pyridinecarboxylate (PAK-200), at 5 microM inhibited the efflux of [3H]vincristine from KB-C2 cells and increased the accumulation of [3H]vincristine in KB-C2 cells to a level similar to that in KB-3 1 cells. PAK-200 inhibited the photoaffinity labeling of P-glycoprotein in KB-C2 membranes by [3H]azidopine. At 5 microM, PAK-200 enhanced the cytotoxic effect of Adriamycin on drug-sensitive KB-3-1 cells, multidrug-resistant KB-8-5 cells, and two human colorectal carcinoma tumor lines, COK-28LN and COK-36LN, by factors of 2, 5, 2, and 3 times, respectively. The calcium antagonistic activity of PAK-200 was about 1000 and 5 times lower than that of another dihydropyridine analogue, nicardipine, and of verapamil, respectively. PAK-200 in combination with Adriamycin completely suppressed the growth of KB-3-1 and COK-36LN and partially suppressed the growth of KB-8-5 but had no significant effect on COK-28LN cells xenografted in nude mice. The level of MDR1 expression of COK-36LN was about 3 times higher than that of COK-28LN, but lower than that of KB-8-5 cells. These results suggest that the interaction of PAK-200 with P-glycoprotein may be partly correlated with the enhancement of the antitumor effect of Adriamycin on xenografted KB-8-5 and COK-36LN cells in nude mice. PMID- 1617640 TI - Interleukin 6 gene transfection into Lewis lung carcinoma tumor cells suppresses the malignant phenotype and confers immunotherapeutic competence against parental metastatic cells. AB - To investigate the influence of interleukin 6 (IL-6) production on malignancy of tumor cells we transfected cells of the high-metastatic, low-immunogenic D122 clone of the Lewis lung carcinoma with a mammalian expression vector containing the human IL-6 complementary DNA. In vitro, IL-6 positive transfectants showed growth inhibition that was directly correlated with the levels of IL-6 production. The in vitro growth arrest did not seem to be a function of an autocrine system mediated via the secreted human IL-6 acting on the tumor cell surface receptors since neutralizing antibodies to human IL-6 did not prevent the growth inhibition. Neither did exogenous human recombinant IL-6 affect the growth of D122 cells. In vivo, IL-6 positive transfectants showed reduction of tumorigenicity and significant suppression of metastatic competence in syngeneic, immunocompetent mice. In mature T-cell deficient nude mice, the IL-6 transfectants showed some arrest of local growth but no suppression of lung metastasis. It seems therefore that the reduction of metastatic competence of IL 6 transfectants is primarily a function of stimulation by the transfectants of host T-cell immune responses. Immunization with inactivated high-positive IL-6 transfectants induced high levels of anti-tumor cytotoxic T-lymphocytes and protected mice against metastatic growth of a subsequent graft of parental tumor cells. Moreover, reduction of metastatic growth of parental highly metastatic D122 cells was also achieved when immunization of mice was begun after establishment of the primary parental tumors. Thus, inactivated IL-6 transfectants were effective when used as a cellular vaccine for experimental immunotherapy of metastasis. PMID- 1617641 TI - Oxidation of methylhydrazines to mutagenic methylating derivatives and inducers of the adaptive response of Escherichia coli to alkylation damage. AB - The methylhydrazines, monomethylhydrazine, 1,1-dimethylhydrazine, and 1,2 dimethylhydrazine, are known carcinogens but only weak mutagens in the Ames test. Chemical oxidation of these compounds by potassium ferricyanide greatly enhanced their mutagenicity to an Escherichia coli ada mutant and converted them into inducers of the adaptive response of E. coli to alkylation damage. Enzymatic oxidation of monomethylhydrazine by horseradish peroxidase-H2O2 also yielded products which induced the adaptive response. Thus, methylhydrazines can be oxidized to active DNA-methylating derivatives which generate methylphosphotriesters (the inducing signal of the adaptive response), O6 methylguanine and/or O4-methylthymine (the miscoding bases repaired by the Ada protein) in DNA. These observations support the suggestion that metabolic oxidation of methylhydrazines in mammalian systems may be required to generate the mutagenic/carcinogenic derivatives. PMID- 1617642 TI - The potential superiority of bromodeoxyuridine to iododeoxyuridine as a radiation sensitizer in the treatment of colorectal cancer. AB - Although the thymidine analogues 5-bromo-2'-deoxyuridine (BrdUrd) and 5-iodo-2' deoxyuridine (IdUrd) have been used successfully as radiation sensitizers in clinical trials, it is not clear which of these agents is the more promising to pursue. To begin to assess this question with regard to colorectal cancer metastatic to the liver, a study was carried out using HT29 human colon cancer cells in culture and implanted in nude mice as xenografts. Cells and animals were treated with BrdUrd +/- the thymidylate synthase inhibitor 5-fluoro-2' deoxyuridine (FdUrd), and the results compared to our previous studies with IdUrd +/- FdUrd (T. S. Lawrence, M. A. Davis, P. E. McKeever, J. Maybaum, P. L. Stetson, D. P. Normolle, and W. D. Ensminger. Cancer Res., 51: 3900-3905, 1991). Using cultured cells, it was found that FdUrd (at concentrations of greater than 10 nM) increased: (a) the incorporation of BrdUrd into the DNA of cultured tumor cells; (b) BrdUrd-mediated radiosensitization; (c) BrdUrd-mediated increase in radiation-induced DNA damage; and (d) BrdUrd-mediated decrease in the repair of radiation-induced damage. The incorporation of BrdUrd was greater than or equal to the incorporation of IdUrd previously determined under the same exposure conditions. Studies using nude mice bearing HT29 xenografts showed that FdUrd increased BrdUrd incorporation more into tumors than into the normal liver. Most tumor cells incorporated BrdUrd (labeling index after a 4-day infusion = 87 +/- 2%; SE); in the liver, labeling was confined chiefly to nonparenchymal cells. In both the presence and absence of FdUrd, the incorporation of BrdUrd into tumors was significantly and consistently greater than the incorporation of IdUrd measured under the same conditions of drug administration (by a factor of 1.2 3.6). Furthermore, the administration of BrdUrd +/- FdUrd tended to produce less weight loss and hematological toxicity than IdUrd +/- FdUrd. These findings suggest that BrdUrd may be superior to IdUrd as a radiation sensitizer in the treatment of colorectal cancer metastatic to the liver. PMID- 1617643 TI - Responsiveness of three newly established human colorectal cancer cell lines to transforming growth factors beta 1 and beta 2. AB - We have established 3 new human colorectal cancer cell lines (LS411N, LS513, and LS1034) from clinical biopsy samples. These lines are tumorigenic and grow s.c. as adenocarcinomas in nude mouse xenografts. Specific marker chromosomes are observed in each line. Carcinoembryonic antigen is expressed at the surface of all 3 lines, but with marked quantitative differences. Indeed, less than 10% of the cells from the HT-29 line used as a reference express carcinoembryonic antigen while more than 90% of the LS1034 cells do so. LS513 and LS1034 consistently express HLA class I antigens and intercellular adhesion molecule 1 which are not detected at the surface of the LS411N cells. No expression of HLA class II antigens DR, DQ, and DP has been measured on any of the lines. All three lines grow well in 5% fetal calf serum medium without addition of exogenous growth factors. The LS1034 line has been adapted to growth in serum-free conditions and exhibits increased clonogenicity when cells are seeded in serum free methylcellulose medium, as compared with medium containing 5% fetal calf serum. The LS513 and LS1034 lines have proved to be of particular interest since they respond to the growth-inhibitory action of TGF-beta 1 and TGF-beta 2 in both liquid and semisolid medium. Both factors were, at pM concentrations, equipotent inhibitors of LS1034 cell proliferation. In contrast, higher concentrations of TGF-beta 1 are inhibitory for proliferation of LS513 cells, whereas TGF-beta 2 has no effect on the growth of these cells in liquid assay. On this basis, using appropriate anti-TGF-beta 1 and anti-TGF-beta 1 IgY, we developed a bioassay for TGF-beta 1 and TGF-beta 2. Two of the three lines have indeed been shown to produce latent-TGF-beta 1 activity. PMID- 1617644 TI - Differentiation of choriocarcinoma cell line (JAr). AB - Choriocarcinoma, a highly malignant tumor arising from the trophoblast, comprises a heterogenous population of cells including cytotrophoblasts, intermediate trophoblasts, and syncytiotrophoblasts. In order to investigate trophoblast differentiation, we used centrifugal elutriation to separate cells from the JAr choriocarcinoma cell line according to their size and to further show that the resultant cell populations differ in their stage of differentiation. Two % of the cell population consists of large, multinuclear cells, which display the highest level of chorionic gonadotropin (CG) mRNAs. The increase in the CG beta mRNA with cell size is a consequence of the transcriptional mechanism, since agents which induce differentiation in JAr cells, i.e., methotrexate, increase the level of CG alpha and CG beta transcripts, cause a shift in cell size, and result in the formation of multinuclear cells. The multinuclear cells in the JAr population arise, at least partly, from kariokinesis without cytokinesis. PMID- 1617645 TI - Evaluation of the wap-ras transgenic mouse as a model system for testing anticancer drugs. AB - Transgenic mouse models have provided many valuable insights into the molecular mechanisms of tumorigenesis; unfortunately, there is a paucity of published information on the utility of these models for evaluating potential anticancer therapeutics. Line 69 wap-ras transgenic mice have an activated, human c-Ha-ras gene on their Y chromosome. Adult males develop salivary and/or mammary adenocarcinomas. Both tumor types express high levels of human ras oncoprotein. Two new sublines, designated wap-ras/F, were created by selective breeding. Subline 69-2 wap-ras/F males developed multiple mammary tumors at puberty. Tumor onset was delayed by cyclophosphamide treatment prior to puberty. Mammary tumors from cyclophosphamide-treated mice weighed 0.57 +/- 0.09 g/mouse (SD +/- SEM; n = 8), while tumors from control mice weighed significantly more at 2.36 +/- 0.25 g/mouse (n = 8; P less than or equal to 0.001; SD +/- SEM). These results suggest that subline 69-2F mice will be valuable for testing therapeutic regimes designed to interfere with processes occurring early in tumorigenesis, before palpable tumor presentation. Tumor sensitivity to several clinically relevant cytotoxins was also tested in adult wap-ras males with palpable tumors. Both salivary and mammary tumors were sensitive to cyclophosphamide and 5-fluorouracil, but not methotrexate. This suggests that wap-ras transgenic mice will indeed be useful in the discovery of novel therapeutics against neoplasia. PMID- 1617646 TI - Elevated level of nuclear protein kinase C in multidrug-resistant MCF-7 human breast carcinoma cells. AB - Previous studies have demonstrated elevated levels of protein kinase C (PKC) activity in multidrug-resistant human breast carcinoma MCF-7/ADR cells compared to control drug-sensitive MCF-7/WT cells (R.L. Fine, J. Patel, and B.A. Chabner, Proc. Natl. Acad. Sci. USA, 85:582-586, 1988). In our present studies, immunohistochemical localization analysis using a polyclonal PKC antibody recognizing the alpha, beta, and gamma subtypes of PKC demonstrates that immunoreactivity is enhanced in MCF-7/ADR cells, with pronounced staining noted in the nuclear region. Other studies with purified nuclei isolated from MCF-7/ADR cells also show a marked increase in the intensity of immunostaining for PKC when compared to nuclei prepared from control MCF-7/WT cells. Western blot analysis of proteins extracted from purified nuclear preparations further establishes an increase in PKC enzyme protein associated with the nuclear fraction of MCF-7/ADR cells. Subcellular fractionation studies also indicate that MCF-7/ADR cells have 4-8 times higher nuclear PKC activity compared to that of control MCF-7/WT cells. MCF-7/ADR cells also possess 3-5-fold elevated cytosolic PKC activity, while a less than 2-fold increase is found in PKC activity associated with the plasma membrane fraction of MCF-7/ADR cells. Examination of these extracts with PKC isotype-specific antisera, as well as by DEAE-cellulose chromatography, reveals that nuclei prepared from MCF-7/ADR cells contain markedly elevated amounts of a slightly altered form of PKC alpha. These results suggest that elevated levels of a modified form of PKC alpha at the nucleus may play a role in modulating nuclear events to promote the development of multidrug resistance in MCF-7 cells. PMID- 1617647 TI - Human immunodeficiency virus type 1 tat gene up-regulates interleukin 4 receptors on a human B-lymphoblastoid cell line. AB - The human immunodeficiency virus type I (HIV-1) regulatory gene, tat III, is a powerful trans-activator of gene expression from the viral long terminal repeat and is essential for HIV replication. In addition, tat III protein has been shown to be immunosuppressive as indicated by the inhibition of antigen mediated T-cell proliferation. To further test whether tat III might play a direct role in the immunosuppressive effects of HIV-1 in addition to its role in virus replication, we examined the regulation of interleukin 4 (IL-4) receptors on a human B lymphoblastoid cell line (Raji) transfected with HIV-1 tat gene (Raji-tat III). We used radioligand receptor binding analysis for cell surface expression and Northern blot analysis for the expression of human IL-4 receptor gene in Raji-tat III cells. Control Raji cells expressed 1383 +/- 361 (SE; n = 3) IL-4 binding sites/cell with a dissociation constant (Kd) of 144 +/- 27 pM (n = 3). However, Raji-tat III cells expressed about three times higher IL-4 receptors (4000 +/- 633 IL-4 binding sites/cell; P less than 0.03 compared to Raji cells) with a similar Kd of 273 +/- 90 pM (n = 3; P greater than 0.05 compared to Raji cells). Whereas both Raji and Raji-tat III cells exhibited a single mRNA species (approximately 4 kilobases) of IL-4 receptors by Northern blot analysis, the mRNA level was about 3-fold higher in Raji-tat III cells compared to Raji cells. Cycloheximide inhibited the expression of IL-4 receptors by 50% in about 2 h in both cell types indicating both the half-life of IL-4 receptors and the requirement for protein synthesis for the tat III up-regulation of IL-4 receptors. Since IL-4 under certain circumstances has been shown to be immunosuppressant, our observation that the HIV-1 tat gene up-regulates IL-4 receptors suggests the possibility that the immunosuppressive effects of HIV-1 are mediated at least in part through IL-4 receptors. PMID- 1617648 TI - p53 mutations in C57BL/6J murine thymic lymphomas induced by gamma-irradiation and N-methylnitrosourea. AB - Genomic DNA from thymus tissue obtained from 47 C57BL/6J animals treated with the DNA alkylating agent N-methylnitrosourea or gamma-irradiation were screened for the presence of p53 mutations by using the single strand conformation polymorphism assay. Mutations were detected in 13% (4 of 30) of primary thymic lymphomas but none of 17 early stage lymphomas. The frequency of p53 mutations was the same in tumors induced by N-methylnitrosourea (2 of 15) or by gamma irradiation (2 of 15). Mutations occurred in the highly conserved regions of the p53 gene in exons 5, 7, and 8. G:C to A:T transitions were commonly observed. One of 4 of the tumors analyzed contained two p53 mutations in exons 7 and 8. A previous study of the same tumors showed that ras mutations occurred with high frequency (greater than 50%) (E. W. Newcomb et al., Cancer Res., 48:5514-5521, 1988). Our data suggest that p53 mutations do not play a major role in carcinogen induced thymic lymphomas studied here. PMID- 1617649 TI - Stimulation of malignant growth in rodents by antidepressant drugs at clinically relevant doses. AB - Tricyclic antidepressants, such as amitriptyline (Elavil), and the nontricyclic agent, fluoxetine (Prozac), bind to growth-regulatory intracellular histamine receptors, associated with anti-estrogen binding sites in microsomes and nuclei. The prototype anti-estrogen binding site/intracellular histamine receptor ligand, N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl, inhibits normal cell proliferation in vitro but stimulates tumor growth in vivo. Because of their structural similarity to N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl, we carried out studies to determine whether amitriptyline and fluoxetine stimulate tumor growth and/or development in rodents at concentrations relevant to the treatment of human depression (equivalent human dose range, approximately 100-150 mg/day for amitriptyline and approximately 20-80 mg/day for fluoxetine). All experiments were performed blinded. In studies of growth stimulation of transplantable syngeneic tumors, groups of mice were inoculated s.c. with C-3 fibrosarcoma cells or given i.v. or s.c. injections of B16f10 melanoma cells, followed 24 h later by daily i.p. injections of saline, amitriptyline, or fluoxetine. Tumor latency (fibrosarcoma), aggregate tumor weight (s.c. injected melanoma), or time to death from pulmonary metastasis (i.v. injected melanoma) was determined; drug-induced stimulation of DNA synthesis in C-3 fibrosarcoma cells in vitro was correlated with tumor growth acceleration in vivo. In a mammary carcinogenesis model, the effects of chronic saline, amitriptyline, or fluoxetine administration on the rate and frequency of development of mammary tumors in rats fed dimethylbenzanthracene (DMBA) were compared. Eight of 20 amitriptyline- or fluoxetine-treated mice developed fibrosarcoma tumors by day 5, as compared to none of 20 saline controls (P less than 0.002). Similarly, 20 of 21 DMBA-treated rats receiving the antidepressant drugs developed 33 mammary tumors by week 15 as compared to 5 tumors in 4 of 7 DMBA-treated rats receiving saline (P less than 0.001). For both models, tumor latency decreased 30-40% and, in the DMBA model, tumor frequency increased greater than 2-fold in the antidepressant-treated rats as compared to controls. Stimulation of fibrosarcoma growth in vivo correlated with a corresponding bell-shaped drug-induced increase in DNA synthesis in vitro. While the median time to death from pulmonary metastases did not differ among groups given i.v. injections of melanoma cells, a significant (P less than 0.01) stimulation of growth of s.c. injected melanoma was observed in mice receiving the antidepressants.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1617650 TI - p53 mutations in basal cell carcinomas. AB - Genomic DNA from 14 basal cell carcinoma biopsies was screened for the presence of mutations in the p53 gene, using the polymerase chain reaction followed by direct DNA sequencing. Heterozygous mutations were detected in 7 of 14 (50%) samples investigated. All mutations were G:C-A:T transitions, and five (71%) of these mutations were transitions at hot spots with CpG sites, three at codon 248 and two at codon 273. The striking similarity of the type of mutations detected in this study and with the UV mutagenesis studies reported in literature suggest the hypothesis that UV may act on the p53 gene in a carcinogenic-specific fashion. PMID- 1617651 TI - Partial characterization of nuclear matrix attachment regions from human fibroblast DNA using Alu-polymerase chain reaction. AB - The proteinaceous nuclear matrix of mammalian cell nuclei has been suggested to be involved in the regulation of chromatin structure, DNA replication, and gene expression. Interaction between cellular DNA and the nuclear matrix is mediated by putative DNA binding sequences, matrix attachment regions (MARs), which may become altered during early events in cellular transformation. Among the cellular changes occurring during the development of neoplasia, all of which may potentially involve the nuclear matrix, are alterations in nuclear structure, loss of control of DNA replication, and significant modifications of cellular gene expression. Therefore, a better understanding of the interaction between DNA and the nuclear matrix is needed. Isolated matrix associated DNA from pulse labeled SV40 transformed human fibroblasts was shown to be enriched in newly replicated DNA, confirming the association of DNA replication with the nuclear matrix as observed by others. Subgenomic fractions of matrix associated DNA enriched in putative MARs sites were prepared from quiescent and logarithmically growing normal human fibroblasts and SV40 transformed human fibroblasts. These fractions of DNA were analyzed by Alu-polymerase chain reaction and agarose gel electrophoresis, revealing complex and unique patterns of DNA products for each cell type investigated. A number of prominent DNA fragments with similar molecular size were found to be present in the amplified DNA products of each DNA source, suggesting that these DNA fragments may represent common DNA sequences which contain MARs sites or which are associated with MARs sites. The application of Alu-polymerase chain reaction to the molecular analysis of nuclear matrix associated DNA may facilitate the isolation and characterization of potentially new human MARs sequences. PMID- 1617652 TI - An altered 11-kilobase transcript in leukemic cell lines with the t(4;11)(q21;q23) chromosome translocation. AB - The 11q23 chromosome band is frequently associated with chromosomal aberrations in human leukemias. We have previously cloned a DNA fragment derived from chromosome 11 which could be used as a probe to detect rearrangements in DNAs from the leukemic cells of patients with the t(4;11), t(9;11), and t(11;19) translocations. In this study we now show that the same probe detects DNA rearrangements in malignant cells from patients with the t(1;11), t(6;11), t(10;11), and del (11q23) chromosomal abnormalities. A second probe obtained from a region located centrometric to the breakpoint cluster detects major and minor transcripts of 12.5 and 11.5 kilobases, respectively, in all cell lines examined. The same probe identifies an altered 11-kilobase RNA in all three independent cell lines with the t(4;11)(q21;q23) chromosome translocation. PMID- 1617653 TI - Gadd45 and Gadd153 messenger RNA levels are increased during hypoxia and after exposure of cells to agents which elevate the levels of the glucose-regulated proteins. AB - We have investigated overlapping activation pathways for two families of stress genes that are expressed in cells exposed to hypoxia. The growth arrest and DNA damage (gadd) genes are induced by DNA damage and irradiation, and their expression is associated with growth arrest. The glucose-regulated proteins (GRPs) are induced by chemical agents that disrupt protein trafficking in the endoplasmic reticulum such as tunicamycin and A23187 and by hypoxia. Here, we demonstrate that the treatment of NIH-3T3 cells with chemical inducers of GRPs results in increased levels of gadd45 and gadd153 mRNA as well as GRP78 mRNA. In addition, hypoxia was also able to increase gadd45, gadd153, and GRP78 mRNA. Therefore the GRP and gadd genes can be activated by similar stimuli (e.g., hypoxia and chemical inducers). However, the mechanisms leading to increased levels of GRP78 and gadd gene mRNA are different and may involve distinct protein kinases. Increased expression of GRPs after treatment with chemical inducers is sensitive to cycloheximide and the protein kinase inhibitors genistein, 2 aminopurine, and H7, whereas the increase in gadd gene mRNA could be blocked by the protein kinase inhibitors H7 and 2-aminopurine but not by genistein or cycloheximide. GRP78 induction occurs by a pathway that requires protein synthesis and is sensitive to genistein, H7, and 2-aminopurine, whereas gadd gene induction is independent of protein synthesis and is inhibited by H7 and 2 aminopurine only. PMID- 1617655 TI - Retraction. T-cell receptor V beta gene expression differs in tumor-infiltrating lymphocytes within primary and metastatic melanoma. PMID- 1617654 TI - Correspondence Re: L.E. Damon et al., Plasma and cerebrospinal fluid pharmacokinetics of 1-beta-D-arabinofuranosylcytosine and 1-beta-D arabinofuranosyluracil following the repeated intravenous administration of high- and intermediate-dose 1-beta-D-arabinofuranosylcytosine. Cancer Res., 51: 4141 4145, 1991. PMID- 1617656 TI - Distribution of misonidazole adducts in 9L gliosarcoma tumors and spheroids: implications for oxygen distribution. AB - The 9L rat gliosarcoma is a widely used experimental brain tumor which has an unusual radiation response. The radiation sensitivity of cells in subcutaneous tumors has been shown to be intermediate between those of aerobic and hypoxic 9L cells in vitro, and cells in spheroids and intracranial tumors appear to be as sensitive as fully aerobic cells. The hypoxic marker misonidazole was used to investigate the distribution of oxygen in these 9L systems. In vitro calibration of binding of [3H]-misonidazole as a function of oxygen concentration demonstrated an inverse relationship similar to those of several other experimental tumors. In autoradiograms of sections from tumors labeled in vivo the grain density rose gradually from the periphery of the tumor to the center. Over millimeter distances the distribution of grains was remarkably uniform, in contrast to the substantial variation reported for several other tumors. The grain density as a function of distance from capillaries was essentially constant. Several interpretations of this result are possible, including the postulate that intermittent blood flow occurs in all 9L tumor capillaries, which results in the majority of the binding of misonidazole occurring during the periods of transient hypoxia. Cells adjacent to the necrotic center in 9L spheroids and the rare necrotic regions in tumors appeared to be severely hypoxic, based on the quantity of misonidazole they bound. Spheroid "cure" experiments demonstrated that these cells were not clonogenic. PMID- 1617657 TI - Long-term growth suppression of human glioma xenografts by chemoimmunoconjugates of 4-desacetylvinblastine-3-carboxyhydrazide and monoclonal antibody 9.2.27. AB - A conjugate of 4-desacetylvinblastine-3-carboxyhydrazide (DAVLBHY) and the glioma reactive monoclonal antibody (mAb) 9.2.27 induced long-term suppression of tumor growth in athymic nude mice engrafted with U87MG human glioma cells. In vitro, DAVLBHY had the strongest antiproliferative activity (inhibitory concentration at which incorporation of [3H]thymidine is at 50% of untreated control is 2.0 x 10( 9) M) of seven cytotoxic drugs tested and so was chosen for conjugation to mAb 9.2.27, which reacts specifically with the core protein of chondroitin sulfate proteoglycans found in human glioblastomas. After conjugation of DAVLBHY to the carbohydrate residues of mAb 9.2.27 it retained its full binding capacity. For in vivo studies, DAVLBHY and several conjugate derivatives were evaluated by using two dosages of i.v. injections, each starting 2 days after s.c. tumor inoculation. The control tumors reached a volume of nearly 3000 mm3 within 30 days. Tumor growth was delayed by about 20 days with four i.v. injections of 0.5 mg/kg 9.2.27-DAVLBHY, which was slightly superior to the unconjugated drug. Moreover, 9.2.27-DAVLBHY produced a highly significant suppression of growth so that the average tumor volume was only 3% of that observed in untreated controls after 28 days. Four injections of this conjugate at a larger dose, 2.0 mg/kg, prevented recurrence of the tumors for 130 days in all animals tested, thus demonstrating a significant increase in the therapeutic index, since the unconjugated drug provided limited inhibition of tumor growth for only 40 days. The specificity of the antitumor effect was demonstrated in a comparison with the control conjugate, KS1/4-DAVLBHY, which despite partial tumor suppression had only a transient effect. The specific antitumor effect of 9.2.27-DAVLBHY was unexpected, since the target antigen is expressed at a relatively low density (40,000 sites/cell) on U87MG glioma cells. PMID- 1617658 TI - Effect of systemic hyperinsulinemia in cancer patients. AB - Data defining the isolated effect of insulin on whole body protein and glucose metabolism in cancer patients are limited. Ten normal volunteers (controls), age 55 +/- 3 years (mean +/- SEM); 8 cancer patients, age 61 +/- 3 years, weight loss 2 +/- 1% (CANWL); and 8 cancer patients, age 55 +/- 2 years, weight loss 18 +/- 2% (CAWL), were studied in the post-absorptive state. Whole body leucine kinetics were determined during a baseline and then a study period during which insulin was infused at 1.0 milliunits/kg/min to achieve a high physiological level of 71 +/- 6, 83 +/- 5, and 64 +/- 5 microunits/ml in controls, CANWL, and CAWL, respectively. Whole body net balance equals protein synthesis minus protein breakdown. Glucose disposal (mg/kg/min) is the rate of D30 infusion at steady state. Glucose disposal of CANWL and CAWL during the study period was significantly (P less than 0.05, analysis of variance) less than controls (3.91 +/- 0.6 in CANWL, 3.66 +/- 1.0 in CAWL, and 5.87 +/- 0.6 mg/kg/min in controls), suggesting resistance to insulin with respect to carbohydrate metabolism. Hyperinsulinemia, under euglycemic and near basal amino acid conditions, significantly reversed the negative postabsorptive leucine net balance (P less than 0.05, analysis of variance) by decreasing protein breakdown in controls as well as weight-stable and weight-losing cancer patients, suggesting that cancer patients are not resistant to the anti-catabolic effect of insulin with respect to whole body protein metabolism. PMID- 1617659 TI - Modulation of ethylnitrosourea-induced toxicity and mutagenicity in human cells by O6-benzylguanine. AB - We have examined the contributions of O6-alkylguanine-DNA alkyl-transferase (AGT) and nucleotide excision repair to the protection of human cells from the toxic and mutagenic effects of ethylnitrosourea. Three human lymphoblastoid cell lines were used: one which possesses both of these DNA repair pathways; one derived from a xeroderma pigmentosum complementation group A patient, which expresses AGT but is deficient in nucleotide excision repair; and a third which does not express AGT but is capable of excision repair. The level of active AGT in the cells was further modulated with the use of the AGT inhibitor, O6-benzylguanine. These cells were exposed to ethylnitrosourea in both the presence and absence of O6-benzylguanine, and population survival, growth, and mutagenesis at the hypoxanthine-guanine phosphoribosyl-transferase locus were measured. The results for all three measurements indicated that the lack of either AGT or nucleotide excision repair significantly impairs the ability of human cells to withstand DNA ethylation damage. Furthermore, the inhibition of AGT in xeroderma pigmentosum group A cells did not increase toxicity or mutagenicity, suggesting that AGT and nucleotide excision repair cooperate in the removal of DNA ethyl adducts. Related studies in our laboratory have shown that AGT and nucleotide excision repair are both necessary for the efficient removal of O6-ethyldeoxyguanosine. PMID- 1617660 TI - Mechanism-related circumvention of acquired cis-diamminedichloroplatinum(II) resistance using two pairs of human ovarian carcinoma cell lines by ammine/amine platinum(IV) dicarboxylates. AB - Acquired resistance to cisplatin has been generated in vitro in two human ovarian carcinoma cell lines: 41M, established from a previously untreated patient; and CH1, from a patient previously treated with cisplatin and cis-diammine-1,1 cyclobutane dicarboxylatoplatinum(II) (carboplatin). In neither cell line with acquired resistance did intracellular detoxification (via increased glutathione or metallothioneins) appear to be a major determinant of resistance. Resistance in 41McisR (resistance factor of 4.7) appeared to be due predominantly to a reduced platinum accumulation (levels were only 23.8% in 41McisR versus 41M). This was also reflected at the DNA level by a similar level of reduced DNA interstrand cross-links and total platinum-DNA adducts measured immediately after a 2-h exposure to cisplatin in 41McisR versus 41M. Conversely, for CH1cisR (resistance factor of 6.5), platinum accumulation, and initial numbers of DNA interstrand cross-links and total DNA-platinum adducts were not significantly different from the parent CH1 line. This is suggestive of a resistance mechanism involving increased DNA repair or tolerance to platinum-DNA adducts operating in the CH1cisR/CH1 pair of lines. Cross-resistance to carboplatin and partial cross resistance to the 1,2-diaminocyclohexane-containing agent, (trans-d,l)-1,2 diaminocyclohexane tetrachloroplatinum(IV) (tetraplatin), was observed in both pairs. However, two novel platinum(IV) ammine/amine dicarboxylates, ammine dibutyratodichloro(cyclohexylamine)platinum(IV) (JM221) and ammine dibenzoatodichloro(propylamine)platinum(IV) (JM244), completely circumvented resistance in 41McisR to produce some collateral sensitivity (resistance factors of 0.67 and 0.54, respectively) but showed cross-resistance in CH1cisR (resistance factors of 3.7 and 4.6). In contrast to the data for cisplatin, intracellular platinum levels were not significantly different between the 41M and 41McisR pair of cell lines after exposure to JM244. These results suggest that the ammine/amine platinum(IV) dicarboxylates, which show considerably greater in vitro cytotoxicity than cisplatin, are capable of circumventing acquired cisplatin resistance which is due to decreased intracellular accumulation but are not able to overcome resistance at the level of DNA platination and removal. PMID- 1617661 TI - Relation of obesity and body fat distribution to endometrial cancer in Shanghai, China. AB - In a case-control study involving 268 cases of endometrial cancer and an equal number of population controls, we assessed the relationship of risk to body weight and fat distribution, examining weight at various ages and current anthropometric measurements. Weight gain during later adulthood and resultant high body masses were important risk predictors, indicating that obesity is an important risk factor, even in an area where the prevalence of obesity and incidence of endometrial cancer are low. Certain fat distribution patterns were related to risk of endometrial cancer independent of general obesity. In particular, fat deposits on the trunk were associated with elevated risks, with the odds ratio for the highest versus lowest quartile of subscapular skinfolds remaining significant even after adjustment for body mass index (odds ratio = 2.9; 95% confidence interval, 1.1-7.3). Central versus peripheral obesity, as measured by the subscapular:triceps ratio, also was related to increased risk, although the association failed to remain significant after adjustment for body mass (highest to lowest quartile, odds ratio = 1.7). In contrast, upper body obesity, as assessed by the waist:thigh ratio, was unrelated to risk. These results support the need for future studies assessing the relationship of hormonal and other biological parameters of fat distribution to assist in identifying causal mechanisms for this tumor. PMID- 1617662 TI - Phase II study of intravenous idarubicin in unfavorable non-Hodgkin's lymphoma. AB - Idarubicin, a new analogue of daunorubicin, was administered i.v. at a dose of 15 mg/m2 to 31 previously treated patients with unfavorable non-Hodgkin's lymphoma. Clinical characteristics included median age, 69 years; performance status, 1; and prior chemotherapeutic regimens, 1. Twenty of the patients were relapsing after prior therapy and 11 were refractory; 29 had received prior anthracycline or anthracenedione. Responses were observed in 43% of patient (3 complete remission and 10 partial remission) with a median duration of 10+ months (2-29+ months). Idarubicin was well tolerated with nonhematological toxicities (nausea/vomiting, mucositis, and anorexia) seen in less than 50% of patients. Median hematological values during the first cycle for this dosage included WBC, 1,300/mm3; platelets, 129,000/mm3; and hemoglobin, 10.9 mg/dl. With dose escalation, hematological toxicity was dose limiting. Symptomatic cardiac toxicity was observed in one patient who had received maximum dose doxorubicin and radiotherapy. Median values for the cardiac ejection fraction during the full course of therapy for the entire group of patients were 0.62 (initial) and 0.60 (final). Idarubicin in i.v. form is an active drug in previously treated patients with unfavorable non-Hodgkin's lymphoma. PMID- 1617663 TI - Inhibition of tobacco-specific nitrosamine-induced lung tumorigenesis in A/J mice by green tea and its major polyphenol as antioxidants. AB - In this study we examined the effects of green tea and its major components, (-) epigallocatechin gallate (EGCG) and caffeine, on the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice. We also studied the effects of green tea and EGCG on O6 methylguanine and 8-hydroxydeoxyguanosine (8-OH-dGuo) formation in lung tissues caused by NNK treatment. Mice were given 2% tea, 560 ppm EGCG, or 1120 ppm caffeine in drinking water for 13 weeks. During this time, NNK (11.65 mg/kg body weight) was administered by gavage three times weekly for 10 weeks from weeks 3 to 12. The bioassay was terminated 6 weeks after the last NNK treatment. Mice treated with NNK developed 22.5 lung adenomas per mouse, whereas NNK-treated mice that drank green tea or EGCG as drinking water developed only 12.2 (P less than 0.01) and 16.1 (P less than 0.05) tumors per mouse, respectively. Mice that drank green tea or caffeine solution showed lower body weight gains, although little difference in water and diet consumption was noted in these groups. While green tea and EGCG exerted little effect on the formation of O6-methylguanine, a critical DNA lesion in NNK lung tumorigenesis, both treatments suppressed the increase of 8-OH-dGuo levels in mouse lung DNA. The inhibition of 8-OH-dGuo formation in lung DNA by green tea and EGCG is consistent with their ability to inhibit lung tumorigenesis by NNK. Because 8-OH-dGuo is a DNA lesion caused by oxidative damage, these results suggest that the mechanism of inhibition by green tea and EGCG in NNK-induced lung tumorigenesis is due at least partly to their antioxidant properties. PMID- 1617664 TI - Tumoricidal activation of murine resident peritoneal macrophages by interleukin 2 and tumor necrosis factor alpha. AB - The capacity of recombinant human interleukin 2 (rH-IL2), alone or in combination with recombinant tumor necrosis factor (r-TNF alpha), to activate murine resident peritoneal macrophages to a tumoricidal state was examined. Resident peritoneal exudate cells from C57BL/6 mice were cultured for 18 h with activating agents and washed and the adherent cells (macrophages) were assessed for cytolytic activity against radiolabeled target tumor cells (EL4, P815). Under these conditions, rH IL2 alone activated macrophages to a tumoricidal state in a concentration dependent fashion. Neither murine nor human r-TNF alpha alone had any activating effect but, when combined with rH-IL2, further stimulated rH-IL2-inducible responses. Using polymyxin B, it was shown that macrophage activation was not due to an inadvertent lipopolysaccharide contamination of the r-TNF alpha or rH-IL2 preparations. It was also unlikely that target cell lysis was a direct result of increased TNF alpha production by rH-IL2 stimulated macrophages since P815 is totally resistant to lysis by r-TNF alpha. Although the lytic effector function was mediated by adherent cells, nonadherent peritoneal exudate cells were required for activation to occur. Furthermore, antisera against murine gamma interferon, when added to activation cultures, reduced the level of cytolytic activity which developed. These data suggest that rH-IL2-induced peritoneal macrophage activation requires stimulation of nonadherent cells and is dependent upon gamma-interferon mediated mechanisms. PMID- 1617665 TI - Identification of novel antimitotic agents acting at the tubulin level by computer-assisted evaluation of differential cytotoxicity data. AB - Data generated in the new National Cancer Institute drug evaluation program, which are based on inhibition of cell growth in 60 human tumor cell lines, were probed with nine known antimitotic agents using the COMPARE algorithm. Cytotoxicity data were available on approximately 7000 compounds at the time of the analysis, and, based on the criteria used, 82 compounds were selected as positive by the computer search. Nine were the probe compounds themselves, and 41 were analogues of known antimitotic agents. Among the remaining 32 compounds there were 19 distinct chemical species. Agents in ten of these groups (containing 20 compounds) were effective inhibitors of in vitro tubulin polymerization and caused the mitotic arrest of cells grown in culture. Two compounds were related natural products binding in the Vinca domain of tubulin, and the others were synthetic agents which interfered with colchicine binding. The remaining 12 agents (one natural product, the remainder synthetic) fell into several groups: two compounds were weak inhibitors of tubulin polymerization, inhibited colchicine binding, and caused mitotic arrest; one compound weakly inhibited tubulin polymerization but did not cause an increase in the number of cells arrested in mitosis; two compounds caused mitotic arrest at micromolar concentrations, but thus far no in vitro interaction with tubulin has been observed; the remainder neither inhibited tubulin polymerization nor caused a rise in the number of cultured cells arrested in mitosis. Tubulin-dependent GTP hydrolysis was stimulated or inhibited by all agents which inhibited tubulin polymerization with the exception of one compound. The analysis of differential cytotoxicity data thus appears to have great promise for the identification of new antimitotic agents with antineoplastic potential. PMID- 1617666 TI - Correlation of loss of alleles on the short arms of chromosomes 11 and 17 with metastasis of primary breast cancer to lymph nodes. AB - To examine the role of loss of heterozygosity (LOH) during tumor development and/or progression, we looked for correlations between metastasis of breast cancer to a regional lymph node(s) and LOH of chromosomal arms 11p, 13q, 16q, 17p, and 17q, where frequent losses in primary tumors have been detected. No correlation between lymph node metastasis and LOH of chromosomes 13q, 16q, or 17q was observed. However, tumors showing LOH of chromosomes 11p (chi 2 = 10.82, P less than 0.01) and 17p (chi 2 = 6.78, P less than 0.01) revealed a significantly higher incidence of metastasis to a regional lymph node(s) than tumors without LOH on these chromosomal arms. Furthermore, only four of 30 (13%) patients with tumors that retained both 11p and 17p had metastasis to a regional lymph node(s), compared with 24 of 32 (75%) patients with tumors that had lost both 11p and 17p. Analysis of LOH with markers on chromosomes 11p and 17p in a large number of tumors indicated that the peritelomeric region of each of these chromosomal arms contains a tumor suppressor gene that may be associated with tumor progression, particularly metastasis to a regional lymph node(s). PMID- 1617667 TI - p53 mutations occur in aggressive breast cancer. AB - Using a polymerase chain reaction-single strand conformation polymorphism approach we analyzed 96 human primary breast tumors for the presence of mutations in exons 2, 5, 6, 7, 8, and 9 of the p53 gene. These exons have been shown to comprise highly conserved sequences and the portion including exons 5 through 9 is believed to be the target for over 90% of the acquired mutations in human cancer. Eighteen tumors of the 96 (18.7%) tested showed reproducibly a variant band indicative of a mutation. Most (15 tumors) of the mutations were single nucleotide substitutions and G:C to A:T transitions were prevalent (6 tumors), G:C to T:A transversions came next (4 tumors), and guanines were always on the nontranscribed strand. Concomitant loss of the wild type allele and mutation of the other copy was observed in only 3 of 18 mutated cases; this is consistent with the heterogeneous cellular composition of breast tumors. Furthermore p53 mutations were correlated to estrogen and/or progesterone receptor negative tumors, thus indicating their relationships to aggressive breast cancer. No association could be observed with DNA amplification events in these tumors. PMID- 1617668 TI - Insulin receptor expression and function in human breast cancer cell lines. AB - We have previously reported that insulin receptor expression is increased in human breast cancer specimens (V. Papa et al., J. Clin. Invest., 85:1503-1510, 1990). In the present study, in order to further understand the role of the insulin receptor in breast cancer, insulin receptor expression and function were characterized in three human breast cancer cell lines, MCF-7, ZR-75-1, and T-47D, and compared to a nonmalignant human breast epithelial cell line, 184B5. Insulin receptor content, measured by radioimmunoassay, was elevated 5- and 3-fold in MCF 7 and ZR-75-1 breast cancer cell lines, respectively, when compared to the nonmalignant cell line 184B5. In contrast, the insulin receptor content of T-47D cells was not increased. The increase in insulin receptor content in MCF-7 and ZR 75-1 cells was not due to amplification of the insulin receptor gene. Also, total insulin receptor mRNA content was not increased in breast cancer cells in respect to nonmalignantly transformed 184B5 breast epithelial cells. However, significant differences in the content of receptor mRNA species were observed. The insulin receptors in the breast cancer cell lines were functional: (a) In all 4 cell lines, high-affinity insulin-binding sites were detected, and, in concert with the insulin receptor radioimmunoassay data, binding capacity was highest in MCF-7 and then in ZR-75-1 cells. (b) In all cell lines, insulin stimulated insulin receptor tyrosine kinase activity. However, the effect of insulin was greater in breast cancer cell lines than in nonmalignant breast cells. (c) In all cell lines, insulin at concentrations of 1 nM or less stimulated [3H]thymidine incorporation. This effect of insulin was inhibited by 50% in MCF-7 cells and by 60% in 184B5 cells when alpha-IR3, a monoclonal antibody to the insulin-like growth factor I receptor, was present. In these cells, therefore, insulin was active via both its own receptor and the IGF-I receptor. In contrast, alpha-IR3 antibody was without effect in T-47D and ZR-75-1 cells, suggesting that in these cell lines insulin acted only via its receptor. In the breast cancer cells, MA-5, an agonist monoclonal antibody to the insulin receptor, stimulated [3H]thymidine incorporation. This present study indicates therefore that in breast cancer cell lines there are functional insulin receptors that regulate breast cancer cell growth. PMID- 1617669 TI - Genetic modification of a murine fibrosarcoma to produce interleukin 7 stimulates host cell infiltration and tumor immunity. AB - Retroviral-mediated gene transfer was used to introduce and express the gene for murine interleukin 7 (IL-7) in a fibrosarcoma tumor (FSA). The tumorigenicity of these genetically modified FSA cells was greatly decreased in immunologically intact syngeneic mice but was unaltered in T-cell-deprived mice. IL-7-infected tumors that did grow in intact animals from large size inocula did so slowly and had a high incidence of spontaneous regression. Furthermore, mice that had rejected tumors became specifically immune to challenge with uninfected parental tumor cells. IL-7-infected FSA growing in intact mice were heavily infiltrated with host T-cells that were presumably responsible for slow growth and tumor regression, and tumor cells were in the minority. Fluorescence-activated cell sorter analysis showed that there was a 530% increase in T-cells in IL-7-infected FSA compared with control tumors. CD8+ T-cells were particularly elevated, but CD4+ lymphocytes were also increased in number, as were eosinophils and basophils. The CD4+:CD8+ ratio in IL-7-infected FSA was 1:1.7 in comparison to 1:0.6 in control tumors. Lymphocytes isolated from IL-7-producing tumors had greatly enhanced cytotoxicity towards uninfected, parental FSA cells. Killing of non-cross-reacting fibrosarcoma line was also increased but to a much lesser extent. Injection of recombinant human IL-7 directly into established FSA tumors slowed their growth and, in a significant number of instances, caused complete regression. Mice that had rejected tumor became specifically immune. The dose that was needed for this effect was, however, somewhat large: 20 micrograms twice daily for 10 days. This result contrasts with the efficacy of IL-7 gene infection in stimulating responses to the same tumor. These considerations make IL-7 a good candidate for tumor-directed cytokine gene therapy. PMID- 1617670 TI - N-ras mutation in ultraviolet radiation-induced murine skin cancers. AB - UV radiation is a potent DNA-damaging agent and a known inducer of skin cancer in experimental animals. To elucidate the role of oncogenes in UV carcinogenesis, we analyzed UV-induced murine skin tumors for mutations in codon 12, 13, or 61 of Ha ras, Ki-ras, and N-ras oncogenes by amplification of genomic tumor DNAs by the polymerase chain reaction followed by dot-blot hybridization to synthetic oligonucleotide probes designed to detect single base-pair mutations. In addition to UV-induced C3H mouse skin tumors, we also analyzed skin tumors induced in the same strain of mice by other carcinogenic agents such as 8-methoxypsoralen + UVA, angelicin + UVA, dimethylbenz-[a]anthracene + UV + croton oil, and 4 nitroquinoline-1-oxide. We found that 4 of 20 UV-induced skin tumors contained either C----A or A----G base substitutions at N-ras codon 61. In addition, 2 of 5 melanomas possessed a G----A transition in N-ras codon 13 and an A----T transversion in N-ras codon 61, respectively. Interestingly, none of the 8 methoxypsoralen + UVA- or angelicin + UVA-induced tumors we analyzed contained mutations in any of the ras genes. However, 1 of 4 4-nitroquinoline-1-oxide induced tumors exhibited a G----T transversion at Ki-ras codon 12, a potential site for formation of a 4-nitroquinoline-1-oxide adduct with a guanine residue. We also found that 2 nonmelanoma tumors induced by dimethylbenz[a]anthracene + UV + croton oil contained an A----T transversion at Ha-ras codon 61 position 2, which is characteristic of most dimethylbenz[a]anthracene-induced tumors. These results suggest that UV-induced C3H mouse tumors display mutations preferentially in the N-ras oncogene. Since most N-ras mutations in UV-induced tumors occurred opposite dipyrimidine sequences (T-T or C-C), one can infer that these sites are the targets for UV-induced mutation and transformation. PMID- 1617671 TI - Mechanism of c-fos induction by active oxygen. AB - We have compared the mechanisms of the transcriptional induction of c-fos in mouse epidermal cells JB6 (clone 30) by an extracellular burst of active oxygen of the type produced by inflammatory phagocytes to induction by serum and phorbol ester. All three inducers elicit a characteristic immediate early response of c fos which is inhibited by the protein kinase inhibitor H7 but enhanced by the protein synthesis inhibitor cycloheximide. Experiments with stable transfectants containing fos 5' upstream regulatory sequences linked to an HSV-tk-chloram phenicol-acetyl-transferase reporter construct indicate that the joint dyad symmetry element-AP-1 motifs exert the most potent enhancer effect in response to active oxygen as well as serum. It is concluded that the different signal transduction pathways used by these inducers converge to the same 5' regulatory sequences of c-fos. In contrast to these common features only active oxygen induction of c-fos required the poly-ADP-ribosylation of chromosomal proteins. The inhibitors of ADP-ribose transferase benzamide and 3-amino-benzamide suppressed the elongation of the c-fos message and the de novo synthesis of nuclear factors, among them c-Fos and c-Jun, which bind to the fos-AP-1 motif in vitro only following stimulation with active oxygen. No active oxygen-induced change was observed in the protein complex which binds to an oligonucleotide containing the SIF and dyad symmetry element motifs in vitro. The presence of Fos and Jun proteins was detected in this complex. Only active oxygen, but not serum or phorbol ester, induces DNA breakage. We propose that poly-ADP-ribosylation is required because it participates in the repair of DNA breaks which interfere with transcription. We observed that Fos protein is weakly poly-ADP-ribosylated in response to active oxygen, but the functional role of this modification remains unclear. PMID- 1617672 TI - Salmonella typhimurium strains expressing human arylamine N-acetyltransferases: metabolism and mutagenic activation of aromatic amines. AB - Epidemiological studies have established the carcinogenic risk of occupational exposure to aromatic amines such as benzidine, beta-naphthylamine, and 4 aminobiphenyl. Metabolic activation of these chemicals to reactive, genotoxic electrophiles, via enzymatic N-oxidation and subsequent conjugation reactions, is necessary for their carcinogenic potential to be realized. Many aromatic amines are mutagenic in prokaryotic test systems, in the presence of exogenous mammalian activating enzymes such as those contained in hepatic 9000 x g supernatant. However, in the Ames (Salmonella typhimurium) assay, induction of mutations by aromatic amines and nitroarenes is also almost completely dependent upon the activity of the endogenous bacterial enzyme, N-acetyltransferase/O acetyltransferase. The relevance of this assay to the prediction of the carcinogenic potential of aromatic amines in humans is thus restricted by the likelihood that the bacterial and human enzymes possess different substrate specificities. In this paper we report the construction and use of new tester strains of S. typhimurium that express high levels of functional human arylamine N-acetyltransferases, NAT1 and NAT2, retaining characteristic arylamine substrate specificities that are distinct from those of the bacterial enzyme. These new strains support the mutagenic activation of benzidine, 2-aminofluorene and 2 amino-3,4-dimethylimidazo[4,5-f]quinoline in the Ames test and may provide a new tool for evaluating the carcinogenic potential of aromatic amines. PMID- 1617673 TI - Distribution of the glucose transporters in human brain tumors. AB - In the present study, we have investigated the expression of both the erythrocyte type (GLUT1) and the brain-type (GLUT3) glucose transporter isoforms in primary human brain tumors. In situ hybridization made it possible to localize and semiquantify both GLUT1 and GLUT3 mRNAs of individual cells in all 18 samples examined. More signals for GLUT3 mRNA than for GLUT1 mRNA were found over astrocytoma cells, while the reverse was the case in all 6 meningiomas. In astrocytomas, for both mRNAs, the density of silver grains over tumor cells was well correlated with the malignancy of the cells. This correlation was, as was also confirmed by Northern blot analysis, more marked with GLUT3 mRNA than with GLUT1 mRNA. In 2 of 5 anaplastic astrocytomas and in all 3 glioblastomas, numerous tumor cells with large amounts of both mRNAs tended to surround the perivascular regions. "Tumor vessels" with endothelial proliferation, an almost pathognomonic feature of glioblastomas, expressed much GLUT3 mRNA but no significant GLUT1 mRNA, while a single- or a few-layered capillary endothelium expressed much GLUT1 mRNA. The distribution of both mRNAs was in good accordance with that of both proteins. Our results suggest that the expression of both glucose transporter isoforms may contribute to the maintenance of human brain tumors and that the expression of the GLUT3 isoform may be closely related to the malignant change of astrocytomas and particularly related to the aberrant neovascularization which accompanies glioblastomas. PMID- 1617674 TI - Complete inhibition of growth followed by death of human malignant melanoma cells in vitro and regression of human melanoma xenografts in immunodeficient mice induced by camptothecins. AB - The plant alkaloid camptothecin and three camptothecin derivatives were used to study responses of human malignant melanoma (BRO) cells xenografted in immunodeficient (nude) mice. Camptothecin and its derivatives 9-nitro-20(S) camptothecin and 9-amino-20(S)-camptothecin inhibited growth of tumors and caused regression in all tumor-bearing mice. Tumor regression was accompanied by degenerative changes in the tumor cells, as assessed by microscopic observations of histological sections prepared from the tumors. No toxic effects were observed in the drug-treated mice, with or without xenografts. In parallel experiments, camptothecin, 9-nitro-20(S)-camptothecin, and 9-amino-20(S)-camptothecin inhibited proliferation of BRO cells in vitro and resulted in dramatic morphological cellular changes comparable to those observed in the sections of solid tumors. The derivative 12-nitro-20(S)-camptothecin had no effect on BRO tumors or cell cultures. The difference between 9-nitro-20(S)-camptothecin and 12 nitro-20(S)-camptothecin is the position at which the NO2 group is attached to the camptothecin molecule. In contrast to BRO melanoma cells, none of the camptothecin derivatives had any effect on cultured human melanocytes, the normal counterparts of melanoma cells. Taken together, the findings indicate that camptothecin and derivatives exert different effects on the growth and morphology of normal and malignant (BRO) melanocytes. PMID- 1617675 TI - Localization of tumors and evaluation of their state of oxygenation by phosphorescence imaging. AB - Oxygen-dependent quenching of phosphorescence has been used to image the distribution of oxygen pressure in small tumors and surrounding tissue. Suspensions of cultured 9L cells or small pieces of solid tumors from 9L cells were injected into the surface of the muscle of the hindquarter of rats, and the tumors were grown until they were 0.2-1.0 cm in diameter. The phosphorescent probe for oxygen was injected into the systemic blood, and phosphorescence was imaged with a video camera. Images of the phosphorescence were collected using a series of different delay times after illumination with a light flash (less than 5-microseconds width at half-height), and the phosphorescence decay constants (lifetimes) and oxygen pressure were calculated for each pixel of the image arrays. The areas of tissue within the tumors were observed to have increased phosphorescence lifetimes and lower oxygen pressures than the surrounding tissue. Phosphorescence imaging is, therefore, a noninvasive optical method which permits quantitation of the distribution of oxygen in small tumors and also, at least in the 9L tumors, differentiation of tumor from normal tissue. PMID- 1617676 TI - Growth inhibition of human glioma cells induced by 8-chloroadenosine, an active metabolite of 8-chloro cyclic adenosine 3':5'-monophosphate. AB - 8-Chloroadenosine 3':5'-monophosphate (8ClcAMP) inhibits the growth of human glioma cell lines at much lower concentrations than more commonly used cyclic AMP analogues, without inducing morphological differentiation. The mechanism by which 8ClcAMP exerts this effect is not fully understood. We examined whether the growth-inhibitory effect of this compound is due to an active metabolite, using a sulforhodamine protein stain assay to determine the proliferation rate of the WF human glioma cell line. 8-Chloroadenosine, one of the metabolites, inhibited the proliferation of WF human glioma cells more potently than 8ClcAMP. In the presence of adenosine deaminase, which converts 8-chloroadenosine into 8 chloroinosine, 8-chloroadenosine no longer inhibited human glioma cell growth. Addition of adenosine deaminase also largely reduced the growth-inhibitory effect of 8ClcAMP, but not of 8-(4-chlorophenylthio)cAMP. High performance liquid chromatography analysis revealed that at least part of the 8ClcAMP in the culture medium is converted into 8-chloroadenosine. We concluded that 8ClcAMP exerts its growth-inhibitory effect through its active metabolite 8-chloroadenosine. Adenylate cyclase assays showed that 8-chloroadenosine does not affect the intracellular cAMP production through adenosine A1 or A2 receptor activation, which makes it unlikely that 8-chloroadenosine inhibits glioma cell growth by increasing the intracellular cyclic AMP concentration. PMID- 1617677 TI - Subcellular distribution of the anticancer drug mitoxantrone in human and drug resistant murine cells analyzed by flow cytometry and confocal microscopy and its relationship to the induction of DNA damage. AB - Flow cytometry and laser scanning confocal imaging have been used to analyze the uptake of the anticancer topoisomerase II poison mitoxantrone by intact mammalian cells and the results correlated with the induction of DNA damage. Unlike Adriamycin, mitoxantrone displays only minimal levels of red fluorescence when excited at 514 wavelength. However, using these excitation and emission conditions, flow cytometry could detect low levels of fluorescence in human transformed fibroblasts exposed to high concentrations (5-20 microM) of mitoxantrone for 1 h. Over this dose range whole cell fluorescence was a function of cell size and increased with drug concentration while drug-induced DNA-protein cross-linking showed saturation. Confocal microscopy revealed the time- and dose dependent appearance of fluorescence, interpreted here as reflecting the disposition of drug molecules, preferentially within the cytoplasm, nuclear membrane, and nucleoli. This pattern contrasted with the intense intranuclear fluorescence observed in Adriamycin-treated human cells. Loss of the nuclear membrane during mitosis resulted in an apparent increase in chromatin-associated fluorescence. Photon counting procedures revealed a predominantly cytoplasmic, possibly lysosomal, location for fluorescence from human cells exposed for 1 h to a low but cytotoxic concentration (0.1 microM, yielding approximately 90% cell kill) of mitoxantrone. At this low concentration, human cells displayed minimal levels of DNA strand cleavage or DNA-protein cross-linking. Murine cells, displaying mitoxantrone resistance as part of the P-glycoprotein-mediated multidrug resistance phenotype, showed specific extinction of mitoxantrone associated fluorescence from inside nuclei but not from within extranuclear compartments. The study demonstrates the feasibility of high resolution studies on the intracellular distribution of mitoxantrone in intact living cells. We suggest a mechanism by which cytoplasmic sequestration of mitoxantrone may be important in determining the response of normal and multidrug-resistant cells as they attempt to progress through mitosis. PMID- 1617678 TI - Herbimycin A, an inhibitor of tyrosine kinase, prolongs survival of mice inoculated with myeloid leukemia C1 cells with high expression of v-abl tyrosine kinase. AB - Herbimycin A, a benzoquinonoid ansamycin antibiotic, reduces intracellular phosphorylation by some tyrosine kinases, including v-abl. The mouse megakaryoblastic cell line C1 expresses v-abl protein at high levels. Herbimycin A at about 20 ng/ml caused 50% inhibition of growth of C1 cells but at 100 ng/ml scarcely affected the growth of another mouse leukemia cell line, M1 cells, or of normal bone marrow cells. Injection of 10(6) C1 cells into nude mice resulted in death of all the mice within 30 days. Administration of herbimycin A significantly enhanced the survival of mice inoculated with C1 cells but scarcely affected the survival of mice inoculated with M1 cells. These results suggest that herbimycin A and/or related compounds may be useful for treatment of some types of leukemia in which tyrosine kinase activity is implicated as a determinant of the oncogenic state. PMID- 1617679 TI - Limonene-induced regression of mammary carcinomas. AB - Dietary administration of the monocyclic monoterpenoid d-limonene causes complete regression of both dimethylbenz[alpha]anthracene- and N-nitroso-N-methylurea induced rat mammary carcinomas. Carcinomas regress when limonene is added to the diet either when the tumor is small and still capable of spontaneously regressing or when it is large and progressed beyond the stage when it is susceptible to spontaneous regression. The limonene dose-tumor regression response relationship is steep. Significant regressions are not observed at 5% dietary levels, while a majority of tumors completely regress above a 7.5% dietary level. Limonene appears to act in a cytostatic fashion. Its removal from the diet results in a significant number of tumor recurrences. Regressing tumors have a unique histopathological appearance that is not associated with gross cytotoxicity, immune cell involvement, or apoptosis. Preliminary analysis suggests a remodeling/redifferentiation event underlying regression. The underlying mechanism of action of limonene in causing tumor regression is unknown. However, it should be noted that limonene can selectively inhibit the isoprenylation of small G proteins. Monoterpenoids such as limonene represent a novel class of anticancer drugs with the potential to cause tumor regressions with limited toxicity. PMID- 1617680 TI - Expression of a transfected H-2Kb gene in B16 cells correlates with suppression of liver metastases in triple immunodeficient mice. AB - In vivo experiments performed with NIH (nu/nu, bg/bg, xid/xid) triple immunodeficient (TD) mice revealed the striking ability of i.v. injected B16-F1 and B16-F10 murine melanoma cells to colonize not only the lungs but also the liver of TD mice. Subsequently, B16 melanoma cell cultures, which express very low levels of H-2Kb antigen, were cotransfected with plasmids pRSVneo, containing the neomycin resistance gene, and 6-2B1pMT, expressing the H-2Kb complentary DNA under the control of the metallothionein enhancer-promoter. Several neomycin resistant clones were analyzed for H-2Kb and H-2Db expression by RNase protection and flow cytometry assays. All parental lines and transfected clones expressed normal levels of H-2Db mRNA, while only some of the transfected clones expressed easily detectable levels of H-2Kb mRNA. Moreover, in these clones H-2Kb expression could be enhanced in the presence of Zn2+, indicating that the metallothionein enhancer was functioning properly. Parental cells and transfected clones were injected i.v. in TD mice to assess the possible involvement of H-2Kb antigen in regulating the metastatic potential of B16 melanoma cells. We observed a remarkable correlation between expression of H-2Kb antigen and suppression of liver-specific metastases in TD mice. Identical results were obtained when we gave TD mice injections of mixed populations of transfectants expressing H-2Kb antigen, obtained by fluorescence-activated cell sorting. These experiments allowed us to rule out the possibility that the observed changes in metastatic potential were due to clonal variability among individual transfected clones. Taken together, the results of our in vivo studies with immunodeficient mice support the notion that specific major histocompatibility complex Class I molecules modulate the metastatic potential of malignant cells also by mechanisms which are independent of their well-established role in antigen presentation. PMID- 1617681 TI - Enhancement of antioxidant and phase II enzymes by oral feeding of green tea polyphenols in drinking water to SKH-1 hairless mice: possible role in cancer chemoprevention. AB - Following the oral feeding of a polyphenolic fraction isolated from green tea (GTP) in drinking water, an increase in the activities of antioxidant and phase II enzymes in skin, small bowel, liver, and lung of female SKH-1 hairless mice was observed. GTP feeding (0.2%, w/v) to mice for 30 days significantly increased the activities of glutathione peroxidase, catalase, and quinone reductase in small bowel, liver, and lungs, and glutathione S-transferase in small bowel and liver. GTP feeding to mice also resulted in considerable enhancement of glutathione reductase activity in liver. In general, the increase in antioxidant and phase II enzyme activities was more pronounced in lung and small bowel as compared to liver and skin. The significance of these results can be implicated in relation to the cancer chemopreventive effects of GTP against the induction of tumors in various target organs. PMID- 1617682 TI - 3-Aminobenzamide can act as a cocarcinogen for ultraviolet light-induced carcinogenesis in mouse skin. AB - Chronic irradiation (three times a week) with ultraviolet B light of the skin of hairless mouse Uscd (Hr) strains resulted in the induction of skin tumors after 25 to 41 weeks. Topical applications of 3-aminobenzamide (3AB; 0.1 or 1 M) after each irradiation significantly shortened the earliest time of onset of tumors to 13 to 25 weeks and increased the number of animals that developed tumors over 41 weeks from 67% without 3AB to 73% and 81% with 0.1 and 1 M 3AB, respectively. 3 Aminobenzamide has previously been shown to inhibit radiation-induced transformation in vitro. In vivo, 3AB has the opposite effect, indicating the need for caution in extrapolating from in vitro systems to carcinogenesis in vivo. PMID- 1617683 TI - Workshop report from the Division of Research Grants, National Institutes of Health. Metal carcinogenesis--a Chemical Pathology Study Section Workshop. PMID- 1617684 TI - Positional identification of fluorine in methyl per-O-acetyl-x-deoxy-x-fluoro alpha-D-hexopyranosides by electron impact and chemical ionisation mass spectrometry. AB - Fully acetylated methyl x-deoxy-x-fluoro-alpha-D-glucopyranosides have been studied using electron impact and ammonia chemical ionisation mass spectrometry. Mass analysed metastable ion kinetic energy spectroscopy (MIKE), collisional activation (CID), and accelerated voltage scanning have been used to evaluate complete fragmentation schemes. Characteristic differences in the fragmentation of positional isomers were noted on analysis of the spectra, and these make it possible to determine the location of fluorine in the molecules studied. Collisionally activated fragmentation of [M-OCH3]+ ions, produced by electron impact, provides an alternative method for localisation of the fluorine atoms. To the contrary, MIKE and CID spectra of [M + NH4]+ cluster ions produced by chemical ionisation did not afford such structural information. PMID- 1617685 TI - Isotope-edited 1D and 2D n.m.r. spectroscopy of 13C-substituted carbohydrates. AB - Three isotope-edited n.m.r. methods have been applied to selectively 13C substituted monosaccharides and nucleosides to simplify their spectra and/or measure 1H-1H, 13C-1H, or 13H-13C spin-couplings detected via the labeled site. 1D INADEQUATE spectra allowed the selective detection of the natural-abundance carbons that are spin-coupled to the labeled carbon, and adjustment of the mixing time permitted further discrimination between one-bond and longer-range 13C-13C coupling pathways. Geminal and vicinal 13C-1H coupling constants were determined from the analysis of 1H-1H COSY cross-peaks for those protons coupled to the labeled carbon. Long-range 13C-(HETCOR) and 1H-detected (HMBC) 13C-1H chemical shift correlation spectra permitted the selective observation of those protons coupled to the labeled site, and JH,H values were measured from data projections. The implications of these methods for structural studies of more complex systems is briefly discussed. PMID- 1617687 TI - Synthesis and antitumour activity of derivatives of curdlan and lichenan branched at C-6. AB - Derivatives of curdlan and lichenan, linear (1----3)-beta-D- and (1----3/1----4) beta-D-glucans, respectively, have been synthesised having alpha-L arabinofuranosyl, alpha-L-rhamnosyl, beta-D-glucosyl, and beta-gentiobiosyl side chains attached at positions 6. These water-soluble derivatives, obtained by condensation of the 2,4- and 2,4-/2,3-di-O-phenylcarbamoyl derivatives of curdlan and lichenan, respectively, with appropriate ortho esters followed by saponification, were characterised by methylation analysis, g.p.c., and interaction with Congo Red. The curdlan derivatives and the lichenan derivative with few glucosyl branches were active against the Sarcoma 180. PMID- 1617686 TI - Synthesis of methyl 2,4-di-O-methyl-3-O-(2-O-methyl-alpha-L-rhamnopyranosyl) alpha-L- rhamnopyranoside and methyl 2,4-di-O-methyl-3-O-[2-O-methyl-3-O-(2-O methyl-alpha-L-fucopyranosyl)- alpha-L-rhamnopyranosyl]-alpha-L-rhamnopyranoside: di- and tri-saccharide segments of a phenolic glycolipid of Mycobacterium kansasii. AB - Syntheses of the title glycosides are described. The critical O-glycosylations were carried out in the presence of boron trifluoride etherate with a high degree of alpha-selectivity. PMID- 1617688 TI - Synthesis and antitumour activity of sulfoalkyl derivatives of curdlan and lichenan. AB - 2-Sulfoethyl, 3-sulfopropyl, and 4-sulfobutyl derivatives of the (1----3)-beta-D glucan curdlan and the (1----3/1----4)-beta-D-glucan lichenan have been synthesised. The substituents are located mainly at positions 6. The curdlan derivatives strongly inhibited the growth of the Sarcoma 180 tumour, whereas the lichenan derivatives were inactive, indicating that a (1----3)-linked beta-D glucan backbone is essential for activity. PMID- 1617689 TI - Multiply 13C-substituted monosaccharides: synthesis of D-(1,5,6-13C3)glucose and D-(2,5,6-13C3)glucose. AB - D-(1,5,6-13C3)Glucose (7) has been synthesized by a six-step chemical method. D (1,2-13C2)Mannose (1) was converted to methyl D-(1,2-13C2)mannopyranosides (2), and 2 was oxidized with Pt-C and O2 to give methyl D-(1,2-13C2)mannopyranuronides (3). After purification by anion-exchange chromatography, 3 was hydrolyzed to give D-(1,2-13C2)mannuronic acid (4), and 4 was converted to D-(5,6-13C2)mannonic acid (5) with NaBH4. Ruff degradation of 5 gave D-(4,5-13C2)arabinose (6), and 6 was converted to D-(1,5,6-13C3)glucose (7) and D-(1,5,6-13C3)mannose (8) by cyanohydrin reduction. D-(2,5,6-13C3)Glucose (9) was prepared from 8 by molybdate catalyzed epimerization. PMID- 1617690 TI - Structural features of a water-soluble arabinoxylan from the endosperm of wheat. AB - A cold-water-soluble wheat-endosperm arabinoxylan consisting of a backbone of (1- --4)-linked beta-D-xylopyranosyl residues that are variously unsubstituted, and 3 or 2,3-substituted with single alpha-L-arabinofuranosyl groups, was subjected to 1H-n.m.r. spectroscopy. The results of 2D homonuclear Hartmann-Hahn and 1D 1H n.m.r. spectroscopy allowed the identification of 3- and 2,3-substituted xylose residues, each with adjacent unsubstituted xylose residues, and also substituted xylose residues with a substituted xylose residue as a neighbour. The 1H-n.m.r. data were correlated with 13C-n.m.r. data by means of a 13C-1H 2D proton-detected heteronuclear multiple-quantum correlation experiment, which showed that only different types of branching (i.e., 3- and 2,3-) can be identified by the 13C n.m.r. data. PMID- 1617692 TI - Mass spectra of some di-D-fructose dianhydride derivatives. PMID- 1617691 TI - Analysis of Macrocystis pyrifera and Pseudomonas aeruginosa alginic acids by the reductive-cleavage method. AB - Permethylated alginic acids comprised of 4-linked D-mannopyranosyluronic acid and 4-linked L-gulopyranosyluronic acid residues undergo reductive cleavage to yield, after acetylation, methyl 3-O-acetyl-2,6-anhydro-4,5-di-O-methyl-D-mannonate (2b) and methyl 3-O-acetyl-2,6-anhydro-4,5-di-O-methyl-D-gluconate (3b) as major products. Small amounts (ca. 13%) of ring-contracted products, namely methyl 2-O acetyl-3,6-anhydro-4,5-di-O-methyl-D-mannonate (9) and methyl 2-O-acetyl-3,6 anhydro-4,5-di-O-methyl-D-gluconate (10), were also observed in these experiments. These results are in marked contrast to previous results on the reductive cleavage of 4-linked D-glucopyranosyluronic acid residues, wherein the ring-contracted product was formed exclusively. Formation of the ring-contracted products could be completely eliminated by reduction (LiAlH4) of ester groups in the permethylated alginic acid prior to reductive cleavage. In the latter experiments, 4,6-di-O-acetyl-1,5-anhydro-2,3-di-O-methyl-D-mannitol (5b) and 4,6 di-O-acetyl-1,5-anhydro-2,3-di-O-methyl-L-gulitol (6b) were the sole products of reductive cleavage of the 4-linked ManA and 4-linked GulA residues, respectively. However, in the previous experiments it was noted that low yields of permethylated alginic acids were obtained and that extensive depolymerization occurred under methylation conditions. Depolymerization could be avoided and higher yields of permethylated polysaccharides could be obtained, by reduction of the carboxyl groups of the alginic acids prior to methylation. Reductive cleavage of the latter polysaccharides yielded the products expected from 4-linked D mannopyranosyl and 4-linked L-gulopyranosyl residues, namely 4-O-acetyl-1,5 anhydro-2,3,6-tri-O-methyl-D-mannitol (13b) and 4-O-acetyl-1,5-anhydro-2,3,6-tri O-methyl-L-gulitol (14b), respectively. Using the latter analytical strategy, it was established that the Macrocystis pyrifera alginate was comprised of 60% 4 linked ManA and 40% 4-linked GulA residues, whereas the Pseudomonas aeruginosa alginate was comprised of 80% 4-linked ManA and 20% 4-linked GulA residues. PMID- 1617693 TI - Synthesis of methyl O-alpha-L-fucopyranosyl-(1----2)-O-beta-D- galactopyranosyl (1----3)-2-acetamido-2-deoxy-beta-D-glucopyranoside, using 2,3,4-tri-O-benzoyl alpha-L-fucopyranosyl bromide as the alpha-L-fucosylating agent. PMID- 1617694 TI - Interstitial cells associated with the deep muscular plexus of the guinea-pig small intestine, with special reference to the interstitial cells of Cajal. AB - Interstitial cells associated with the deep muscular plexus of the guinea-pig small intestine were studied by electron microscopy, and three-dimensional cell models were reconstructed from serial ultrathin sections with a computer graphic system. Three types of cells were recognized. The first type was similar in shape to smooth muscle cells, but did not contain an organized contractile apparatus. Many large gap junctions comprising about 4% of the cell surface were present; they connected cells of the first type to each other, to the second type of cell and to smooth muscle cells of the outer circular layer. The second type of cell had a well-demarcated cell body with long slender processes and was characterized by a large amount of glycogen comprising about 9% of the cell volume. The third type of cell was similar to fibroblasts, and contained well-developed Golgi apparatus and rough endoplasmic reticulum. Some of these fibroblast-like cells (a possible subtype) formed small gap junctions. All three types of cells showed close relationships with nerve varicosities. This cellular network consisting of gap-junction-rich cells, glycogen-rich cells and smooth muscle cells may be involved in the pacemaking activity of intestinal movement. PMID- 1617695 TI - Progressive redistribution of alcohol dehydrogenase during vitellogenesis in Drosophila melanogaster: characterization of ADH-positive bodies in mature oocytes. AB - The use of monoclonal antibodies against Drosophila alcohol dehydrogenase (ADH) provides a powerful tool in the analysis of the tissue and temporal patterns of Adh gene expression. Immunocytochemical techniques at the light- and electron microscopic levels have been used to determine the distribution of ADH in the ovarian follicles of D. melanogaster during oogenesis. In the early stages of oogenesis, small amounts of ADH are detectable in the cystocytes. At the beginning of vitellogenesis (S7), ADH appears to be located mainly in the nurse cells. From stage S9 onwards, the ADH protein is evenly distributed in the ooplasm until the later stages of oogenesis (S13-14), when multiple ADH-positive bodies of varying size appear in the ooplasm. This change in distribution is a result of the compartmentalization of the ADH protein within the glycogen yolk or beta-spheres. Yolk becomes enclosed within the lumen of the primitive gut during embryonic development, and thus our results suggest a mechanism for the transfer of maternally-inherited enzymes to the gut lumen via yolk spheres. PMID- 1617696 TI - Morphological differentiation of endothelial cells co-cultured with astrocytes on type-I or type-IV collagen. AB - In this study bovine aortic endothelial cells were co-cultured with astrocytes from fetal Wistar Kyoto rats. Endothelial cells growing on type-I collagen, co cultured with astrocytes, showed various stages of development. Although some cells appeared to be mature, horseradish peroxidase penetrated within 1 min of incubation through the intercellular junctions of these endothelial elements maintained on type-I collagen. In contrast, endothelial cells on type-IV collagen, co-cultured with astrocytes, were well developed; their intercellular junctions were well established, and plasmalemmal vesicles reduced in number. As a result, horseradish peroxidase was unable to penetrate through the endothelial cells grown on type-IV collagen and co-cultured with astrocytes because of the reduced extent of the junctional and vesicular transport. These findings reveal that (1) type-IV collagen is essential for the differentiation of endothelial cells, (2) endothelial cell-astrocyte interactions occur during co-culture, and (3) endothelial permeability depends on astrocyte-produced factors, in addition to type-IV collagen. PMID- 1617697 TI - Ultrastructure of the basement membrane and its precursor in developing rat submandibular gland as shown by alcian blue staining. AB - The ultrastructure of the epithelial basement membrane and membrane precursor was studied in rat submandibular rudiment and a model system of the reconstructed basement membrane, by transmission electron microscopy following alcian blue staining. Directly beneath the epithelial plasma membrane, a meshwork layer was found to consist of anastomosing thin fibers arranged as a three-dimensional meshwork (100-400 nm in thickness). Straight strands (5-10 nm in diameter) could sometimes be seen to pass through the meshwork. Adjacent to this layer, a coarse network composed of threads (20-40 nm in diameter) connected the meshwork layer with collagen fibers of the underlying connective tissue. The earliest precursors recognized in the reconstruction-model system were part of the fine-meshwork structure, and showed this structure to be a fundamental component of the basement membrane. PMID- 1617698 TI - 12-O-tetradecanoylphorbol-13-acetate induces selective desquamation of superficial cells in rat urinary bladder epithelium. AB - 12-O-tetradecanoylphorbol-13-acetate (TPA) is known to affect the proliferation and/or differentiation of several types of cells. We injected TPA directly into the lumen of rat bladder to determine, using scanning and transmission electron microscopy, its effects on the bladder epithelium in vivo. At 1 h after TPA injection (1 microgram/ml), the superficial cells of the epithelium had changed their morphology, and large spherical vacuoles occupied their cytoplasm. In some areas, the underlying intermediate cells were exposed by the desquamation of the superficial cells. During the next few hours, TPA was excreted from the bladder lumen by voluntary micturition, but the desquamation of the superficial cells proceeded further. All the superficial cells were lost from the luminal surface by 24 h after TPA injection. The changes noted were specific for the superficial cells and were not observed in the intermediate or basal cells. After 24 h, part of the epithelium had a three-layer structure, indicating that regeneration was taking place. These results demonstrate that TPA selectively affects and desquamates superficial cells in a short period of time. This experimental system may be useful for studying in vivo cell proliferation and/or differentiation. PMID- 1617699 TI - Structural changes in condylar cartilage following prolonged exposure to the human parathyroid hormone fragment (hPTH) 1-34 in vitro. AB - This investigation presents the structural changes in condylar cartilage incubated in the presence of human parathyroid hormone (1-34) in an organ culture system for 6 to 12 days. Control cultures maintained their cartilaginous characteristics whereas human parathyroid hormone (1-34)-treated cultures revealed the following modifications: (1) The chondroprogenitor cell zone at the apical region of the explant underwent a substantial enlargement. The cells changed from a mesenchyme-like morphology into polygonal, glycogen-rich cells that were tightly attached to each other by a fibrillar intercellular matrix, but even by 12 days the apical region was comprised of healthy cells. (2) The mineralizing zone in the hypertrophic cartilage revealed a change in its cellular population. Hypertrophic chondrocytes were replaced by cells with amoeboid extensions and large numbers of secretory granules or vesicles. Based upon the above findings it appears that the chondroprogenitor cells that are initially stimulated to proliferate, are being suppressed from subsequent differentiation into chondroblasts; and that hypertrophic chondrocytes apparently undergo a dedifferentiation process followed by development into an as yet unknown cell population. PMID- 1617700 TI - Cellular changes in rat parathyroids provoked by progesterone and testosterone. AB - Male rats kept on a standard diet were treated either with progesterone or testosterone by a single intramuscular injection of preparations which are slowly absorbed and metabolized. The rats were anaesthetized 24 h after application of the hormones, perfused with glutaraldehyde, and the parathyroid glands prepared for electron microscopy. Morphometric analysis revealed that both progesterone and testosterone provoked (1) an increment in nuclear and cell volume and a concomitant increment in cell surface area, and (2) an increment in surface area of rough endoplasmic reticulum by 42% and 49%, and of the Golgi complex by 85% and 63%, respectively. Previously, we had found that oestradiol treatment led to a similar response in parathyroid cells. The conclusion is thus drawn that male and female sex hormones induce membrane synthesis resulting in an enhanced capacity for parathyroid hormone secretion since RER and Golgi complex are concerned with this secretion. It is considered probable that sex hormones have the ability fundamentally to modulate secretory activity in parathyroid cells. PMID- 1617701 TI - Octopamine-immunoreactive neurons in the central nervous system of the cricket, Gryllus bimaculatus. AB - The distribution of octopamine-immunoreactive neurons is described using whole mount preparations of all central ganglia of the cricket, Gryllus bimaculatus. Up to 160 octopamine-immunoreactive somata were mapped per animal. Medial unpaired octopamine-immunoreactive neurons occur in all but the cerebral ganglia and show segment-specific differences in number. The position and form of these cells are in accordance with well-known, segmentally-organized clusters of large dorsal and ventral unpaired medial neurons demonstrated by other techniques. In addition, bilaterally arranged groups of immunoreactive somata have been labelled in the cerebral, suboesophageal and terminal ganglia. A detailed histological description of octopamine-immunoreactive elements in the prothoracic ganglion is given. Octopamine-immunoreactive somata and axons correspond to the different dorsal unpaired medial cell types identified by intracellular single-cell staining. In the prothoracic ganglion, all efferent neurons whose primary neurites are found in the fibre bundle of dorsal unpaired cells are immunoreactive. Intersegmental octopamine-immunoreactive neurons are also present. Collaterals originating from dorsal intersegmental fibres terminate in different neuropils and fibre tracts. Fine varicose fibres have been located in several fibre tracts, motor and sensory neuropils. Peripheral varicose octopamine immunoreactive fibres found on several nerves are discussed in terms of possible neurohemal releasing sites for octopamine. PMID- 1617702 TI - Uptake and intracellular transport of cationic ferritin in the bronchiolar and alveolar epithelia of the rat. AB - Cationic ferritin was used as a marker to reveal the processes of endocytosis and intracellular transport in bronchiolar and alveolar epithelia. The marker was injected into the lung via the trachea, and ultrastructural observation of the distribution of ferritin particles in bronchiolar and alveolar epithelial cells was carried out at intervals of 5, 15, 30 and 60 min after the injection. The luminal surface of the airway and the alveolar epithelium showed diffuse labeling with cationic ferritin. In general, ferritin particles were observed in vesicles and vacuoles of the bronchiolar and alveolar epithelial cells within 5 min of injection; they appeared in multivesicular bodies within 15 min. Multivesicular bodies and secondary lysosomes containing ferritin particles, some of which showed a positive reaction for acid phosphatase, were seen in the basal cytoplasm within 30 min; ferritin particles appeared in the basal lamina below the Clara cells, ciliated cells and type 2 alveolar cells within 30 min. Ferritin particles were seen in ovoid granules of some Clara cells and in lamellar inclusion bodies of many type 2 alveolar cells. Brush cells and type 1 alveolar cells took up only a small quantity of ferritin particles. PMID- 1617703 TI - Intercellular communication between cultured granulosa cells of the marmoset (Callithrix jacchus). AB - The influence of follicle-stimulating hormone, forskolin, insulin-like growth factor type I, epidermal growth factor, and 12-tetradecanoyl-phorbol-13-acetate on marmoset granulosa cell communication via gap junctions was investigated by morphological means and microinjection of carboxyfluorescein. Gap junctions between neighbouring granulosa cells were present in all groups. The number, but not length, of gap junctions between marmoset granulosa cells increased when the cells had been treated with follicle-stimulating hormone, insulin-like growth factor type I, and follicle-stimulating hormone plus insulin-like growth factor type I. No effect on gap junctions was seen, after exposure of the cells to the other three substances. Carboxyfluorescein and counting of the surrounding labelled cells showed that supplementation with follicle-stimulating hormone, forskolin, insulin-like growth factor type I and epidermal growth factor from the beginning of cultivation led to an increase in stained cells after 48 h. When treatment was started in 48 h cultures the substances reached their maximal activity within 30 min (forskolin and epidermal growth factor) or 3 h (follicle stimulating hormone and insulin-like growth factor type I). Spreading of the fluorescent dye was inhibited when the medium was supplemented with 12 tetradecanoyl-phorbol-13-acetate. This effect was maximal after 30 min. Additive effects regarding the coupling of the cells were seen by combining of epidermal growth factor with follicle-stimulating hormone, but not with insulin-like growth factor type I or forskolin plus follicle-stimulating hormone. PMID- 1617704 TI - Transient serotonin-immunoreactive neurons coincide with a critical period of neural development in coho salmon (Oncorhynchus kisutch). AB - In coho salmon (Oncorhynchus kisutch), smolt transformation has been shown to be associated with sequential surges of neurotransmitters in the brain. In order to determine if the surge of serotonin (5-HT) is correlated with structural changes, we have used immunocytochemistry to observe changes in the serotonin immunoreactivity before, during and after the 5-HT surge. The following stages were studied: 12-month-old freshwater presmolts, 17-month-old freshwater presmolts, 18-month-old saltwater smolts, 19-month-old saltwater postsmolt, 24 month-old postsmolt, and adult spawners. In the 17-month-old samples, but not at any other stage, we found a set of transient (serotonin-immunoreactive) 5-HT immunoreactive neurons in the lateral preoptic area, as well as a discrete population of 5-HT-immunoreactive neurons in the lateral part of the dorsal right habenular nucleus. In addition, a higher density of serotonergic fibers was found in the telencephalon at this stage compared to the following two stages. Since the transient 5-HT-immunoreactive structures presented here do not appear simultaneously with the 5-HT total brain concentration surge, we conclude that they are unlikely to be the source of the 5-HT surge, but are probably related to other developmental changes in the brain associated with smolt transformation. PMID- 1617706 TI - Initial and long-term results of percutaneous transluminal coronary angioplasty in patients 75 years of age and older. AB - In 212 patients aged 75 years and older the immediate and long-term results of percutaneous transluminal coronary angioplasty (PTCA) were assessed. For 293 stenoses the primary angiographic success rate was 96% and the overall clinical success rate was 90.6%. Angioplasty caused a myocardial infraction in 7 patients (3.3%), 2 patients (0.9%) needed emergency aorto coronary bypass surgery, and 4 patients (1.9%) died following the procedure. Actuarial 7 year survival was calculated at 69.3% with a standard deviation (SD) of 8%. Actuarial cardiac survival at 7 years was 92.1% (SD 3%), whereas non-cardiac survival at 7 years was 75.3% (SD 9%). Actuarially, at 7 years 98.5% (SD 1%) were estimated to remain free from myocardial infarction in the angioplasty-related area, 95.7% (SD 2%) to remain free from any myocardial infarction, 93.9% (SD 2%) to remain free from re PTCA because of a recurrence, 84.7% (SD 5%) to remain free from any re-PTCA, and 97.1% (SD 2%) to remain free from (re)-operation. Fifty-two point three percent (SD 8%) were estimated to remain free from any cardiac event. If recurrence of angina is taken into account, only 25.8% (SD 13%) remain asymptomatic during 7 years follow-up. After successful angioplasty in patients aged 75 and older the chance of remaining free from any event or angina at 7 years actuarial follow-up gets as low as 15.7% (SD 9%). We conclude that in selected elderly patients angioplasty can be performed with a high success rate, although the periprocedural mortality and morbidity appear to be higher than in the younger age group. During long-term follow-up, most of the patients remain free of cardiac events and survival appears to be largely dependent on noncardiac factors. However, long-term relief from angina is probably less than in younger patients. PMID- 1617705 TI - Granulated metrial gland cells in the pregnant uterus of mice expressing the collagen mutation tight-skin (Tsk/+). AB - Influences of the extracellular matrix (ECM) on the differentiation and distribution of granulated metrial gland (GMG) cells, a uterine natural killer (NK)-like cell subset, were studied by histological examination of implantation sites in the mouse mutant Tsk/+. Tsk/+ mice overproduce collagens I and III. GMG cell differentiation appeared to progress normally in Tsk/+ mice between days 6.5 and 12.5 of gestation. The distribution of GMG cells, however, was abnormal. Significant numbers of GMG cells were found in the antimesometrial and lateral decidual regions at day 8.5 of gestation and in the regions between implantation sites until day 10.5 of gestation. Loss of GMG cells from these regions normally occurs by day 6.5 of gestation. These data suggest that alterations to the ECM change the migration properties or life span of GMG cells. PMID- 1617707 TI - Coronary stenting: single institution experience with the initial 100 cases using the Palmaz-Schatz stent. AB - We studied 100 patients who had coronary implantation of Palmaz-Schatz stents in our institution from November 1989 until March 1991. A total of 126 standard and 6 short stents were implanted. The patients' mean age was 58 +/- 5 years, and 97 were males. The indications were lesions with high risk of restenosis (29 patients), restenosis (27 patients), suboptimal result of angioplasty (24 patients), dissection (16 patients), and recanalized chronic total occlusion (6 patients). In 17 patients a brachial cut-down approach was used. Stents were correctly placed in 98 patients. Stent related complications occurred in 9 patients: major ischemic complications in 7 patients (acute myocardial infarction in 2 patients, emergency bypass surgery in 3 patients and emergency angioplasty in 2 patients); in 3 of these patients there was a subacute closure of the stent and in 2 patients there were delivery problems. Vascular complications at the site of arterial puncture occurred in 3 patients (some patients had more than one complication). A learning curve was observed. There was a decrease in the complication rate with the higher number of patients treated: 28% for the first 50 patients and 6% for the last 50 patients. Clinical follow-up was available in all patients. Of the 92 patients eligible for follow-up (7 +/- 2 months), 69 patients were asymptomatic and 23 had recurrence of angina: 19 patients for stent restenosis and 4 patients for coronary artery disease progression. Follow-up angiogram was done in 79/92 (86%) patients: 21 had restenosis (27%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617708 TI - Multicenter dose-finding trial for thrombolysis with urokinase preactivated pro urokinase (TCL 598) in acute myocardial infarction. German Preactivated Pro Urokinase Study Group. AB - In a multicenter dose-finding study, the thrombolytic potency of urokinase preactivated pro-urokinase was evaluated. Sixty-two patients were randomly assigned to receive 250,000 U of urokinase plus either 4.5 mega U (group I: n = 33) or 6.5 mega U (group II: n = 29) of pro-urokinase. Patency rates were 36.4% (20.4-54.9%) vs. 54.5% (36.3-71.9%) (n = 27) at 60 minutes and 55.6% (32.5-70.6%) vs. 62.1% (42.3-79.3%) at 90 min into thrombolysis (n.s.). In a third group of 12 patients treated with 500,000 U of urokinase plus 6.5 mega U of pro-urokinase patency was achieved in 33.3% (9.9-65.1%) and 41.7% (15.2-72.3%) at 60 and 90 min, respectively. Patency rates at 24 hr follow-up angiography (n = 35) were 78.6% (49.2-95.3%), 85.7% (57.2-98.2%), and 85.7% (42.1-99.6%). Coagulation analysis in 37 patients revealed similar alterations in the three treatment groups with minor decreases in fibrinogen levels, moderate drops in plasminogen and alpha-2-antiplasmin levels, and moderate increases in the concentrations of the total fibrinogen/fibrin degradation products, the differences between the groups not being significant. Bleeding complications were observed in 12.9%, 13.8%, and 25% of patients in groups I, II, and III, respectively, mainly related to catheter sites. Hence, the safety profile of urokinase preactivated pro urokinase seems comparable to other thrombolytic regimens. Reopening of occluded coronary arteries, however, is achieved relatively slowly. Thus, in its use for thrombolysis in myocardial infarction, urokinase preactivated pro-urokinase does not seem to offer superior advantages. PMID- 1617709 TI - Maximum stress-volume index ratio of the left ventricle in hypertrophic cardiomyopathy. AB - To evaluate the left ventricular contractile state in patients with nonobstructive hypertrophic cardiomyopathy (HCM), we analyzed the maximum stress volume index ratio (MSVR) using catheter-tip cineangiography in 11 patients with HCM and 16 normal subjects. The value of the MSVR in normal subjects was 6.48 +/- 1.25 kdyn/cm5/m2 (mean +/- SD) and we defined the range of the mean +/- 2 SD as the normal MSVR range. Six patients with HCM placed inside the normal MSVR range (IN), but the other 5 patients placed outside and to the right of the normal range (RIGHT). This suggests that the contractile states of the patients of the RIGHT group were depressed. Compared with IN, the end-diastolic and end-systolic volume indices of RIGHT were larger (EDVI; 69.3 +/- 6.9 vs. 96.1 +/- 11.1 ml/m2, p less than 0.01, ESVI; 18.2 +/- 3.2 vs. 29.1 +/- 8.3 ml/m2, p less than 0.05), but the ejection fraction did not differ (IN 73.5 +/- 5.7 vs. RIGHT 69.6 +/- 8.3%, NS). End-diastolic pressure of IN and RIGHT was higher than that of normal subjects (IN 16.5 +/- 4.5, RIGHT 16.7 +/- 4.6 vs. 8.3 +/- 2.5 mm Hg, both p less than 0.05), but there was no difference between the two groups in HCM. End systolic pressure did not differ among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617710 TI - Enough with the fantastic voyage: will IVUS pay in Peoria? PMID- 1617711 TI - Ambiguous coronary angiography: clinical utility of intravascular ultrasound. AB - We report the use of intravascular ultrasound (IVUS) in situations where angiography was ambiguous or uncertain in assessing the significance of coronary stenoses. The indications for performing intravascular ultrasound were 1) angiographic findings did not correlate with the clinical presentation (n = 5) and 2) the lesion was not seen well by angiography because of overlapping vessels at the site of suspected stenosis (n = 3). We studied eight lesions in seven patients. Six nonobstructive stenoses on angiography were shown by IVUS to be significant. In two patients, stenoses were thought to be significant on angiography, but, due to overlapping of the vessels, there was doubt regarding the severity of the narrowing. In these two patients, IVUS clearly showed that the lesions were nonobstructive. As seen from the above results, angiography underestimated 6/8 stenoses and overestimated in 2/8 stenoses when compared to IVUS. We conclude that IVUS can be used to clarify ambiguous angiographic findings which can have a major impact on the clinical decision making. PMID- 1617712 TI - Interpretation of cardiac pathophysiology from pressure waveform analysis: coronary hemodynamics, Part III: Coronary hyperemia. AB - Basal patterns (systolic/diastolic components) of coronary flow velocity as previously described are generally maintained during hyperemia and can be easily recorded in the catheterization laboratory during pharmacologic stimulation. The interpretation of the clinical significance of coronary vasodilatory reserve may be complicated by both coronary and myocardial diseases. Distal coronary artery hyperemic responses measured with ultrasound Doppler-tipped guidewires will provide new information on traditional observations of coronary physiology in humans. PMID- 1617713 TI - Intracoronary thrombus: chronic urokinase infusion and evaluation with intravascular ultrasound. AB - Percutaneous revascularization of coronary arteries with intraluminal thrombi is a clinical problem. We report a patient in whom we administered prolonged infusion of intracoronary urokinase and then assessed the stenosis with intravascular ultrasound before and after atherectomy. We found both angiography and intravascular ultrasound to be misleading in determining the presence of residual thrombus after thrombolysis. PMID- 1617714 TI - Ultrasound guided ablation of pseudoaneurysm following coronary artery stent placement: a preliminary report. AB - A femoral artery pseudoaneurysm in a 47 year old woman following coronary artery stent placement was treated with color-flow duplex ultrasound guided compression. This technique may be useful following stent placement because of the requirement for continued anticoagulation post-procedure. PMID- 1617715 TI - Complete heart block complicating retrograde left-heart catheterization of patients with cardiac allografts. AB - The development of complete heart block during left-sided cardiac catheterization is an uncommon event. We describe three cases of complete heart block complicating left-sided cardiac catheterization of patients with cardiac allografts. Review of the cases performed at our institution suggests that complete heart block during left-sided catheterization may be more common in patients with cardiac allografts. PMID- 1617716 TI - Sequential proximal and distal infusion of urokinase resulting in recanalization of acutely occluded aortocoronary bypass graft after coronary angioplasty. PMID- 1617717 TI - Percutaneous transfemoral spring coil embolization of a pseudoaneurysm of the femoral artery. AB - Pseudoaneurysm of the femoral artery is a possible complication of percutaneous transfemoral catheterization. Its typical treatment has been open surgical repair. This article describes a new technique for the treatment of femoral artery pseudoaneurysm by spring coil embolization. PMID- 1617718 TI - Interpretation of cardiac pathophysiology from pressure waveform analysis: aortic regurgitation. PMID- 1617719 TI - Initial experience with a new compression device for hemostasis after femoral arterial puncture. AB - We evaluated a new hemostasis device to maintain focused pressure over the femoral artery puncture site for 2-6 hours in 330 cases after diagnostic catheterization or coronary angioplasty. No patient developed later hematoma or vascular complications. The initial favorable experience suggests that this hemostasis device has advantageous features of stability and site visualization and is a suitable adjunct to current methods of maintaining puncture site pressure after brief manual compression following arterial catheterization. PMID- 1617720 TI - Congenital atresia of left main coronary artery. PMID- 1617721 TI - Diagnostic coronary arteriography. PMID- 1617722 TI - Movement and resolution of Holliday junctions by enzymes from E. coli. AB - RuvA and RuvB act together to move Holliday junctions. RuvC cleaves Holliday junctions and apparently acts in concert with RuvA and RuvB. RecG can substitute for RuvABC in the RecBCD pathway of recombination but not in the RecF pathway. PMID- 1617723 TI - Wnt genes. PMID- 1617724 TI - The level of CD8 expression can determine the outcome of thymic selection. AB - During thymic development, thymocytes that can recognize major histocompatability complex (MHC) molecules on thymic epithelial cells are selected to survive and mature (positive selection), whereas thymocytes that recognize MHC on hematopoietic cells are destroyed (negative selection). It is not known how MHC recognition can mediate both death and survival. One model to explain this paradox proposes that thymocytes whose T cell antigen receptors (TCRs) recognize MHC with high affinity are eliminated by negative selection, whereas low affinity TCR-MHC interactions are sufficient to mediate positive selection. Here we report that, while the expression of a 2C TCR transgene leads to positive selection of thymocytes in H-2b mice, expression of both a CD8 transgene and a 2C TCR transgene causes negative selection. This observation indicates that quantitative differences in TCR-MHC recognition are a critical determinant of T cell fate, a finding predicted by the affinity model for thymic selection. PMID- 1617726 TI - Architecture and design of the nuclear pore complex. AB - A three-dimensional analysis of the nuclear pore complex reveals the underlying, highly symmetric framework of this supramolecular assembly, how it is anchored in the nuclear membrane, and how it is built from many distinct, interconnected subunits. The arrangement of the subunits within the membrane pore creates a large central channel, through which active nucleocytoplasmic transport is known to occur, and eight smaller peripheral channels that are probable routes for passive diffusion of ions and small molecules. PMID- 1617725 TI - CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor component gp130. AB - Ciliary neurotrophic factor (CNTF) has a variety of actions within the nervous system. While some of the actions of leukemia inhibitory factor (LIF) on neurons resemble those of CNTF, LIF also has broad actions outside of the nervous system that in many cases mimic those of interleukin-6 (IL-6). Comparison of the tyrosine phosphorylations and gene activations induced by CNTF and LIF in neuron cell lines reveals that they are indistinguishable and also very similar to signaling events that characterize LIF and IL-6 responses in hematopoietic cells. We provide a basis for the overlapping actions of these three factors by demonstrating that the shared CNTF and LIF signaling pathways involve the IL-6 signal transducing receptor component gp130. Thus, the receptor system for CNTF is surprisingly unlike those used by the nerve growth factor family of neurotrophic factors, but is instead related to those used by a subclass of hematopoietic cytokines. PMID- 1617727 TI - Mutations at the 3' splice site can be suppressed by compensatory base changes in U1 snRNA in fission yeast. AB - U1 snRNA is an essential splicing factor known to base pair with 5' splice sites of premessenger RNAs. We demonstrate that pairing between the universally conserved CU just downstream from the 5' junction interaction region and the 3' splice site AG contributes to efficient splicing of Schizosaccharomyces pombe introns that typify the AG-dependent class described in mammals. Strains carrying mutations in the 3' AG of an artificial intron accumulate linear precursor, indicative of a first step block. Lariat formation is partially restored in these mutants by compensatory changes in nucleotides C7 and U8 of U1 snRNA. Consistent with a general role in fission yeast splicing, mutations at C7 are lethal, while U8 mutants are growth impaired and accumulate linear, unspliced precursor to U6 snRNA. U1 RNA-mediated recognition of the 3' splice site may have origins in analogous intramolecular interactions in an ancestral self-splicing RNA. PMID- 1617728 TI - ATP-dependent branch migration of Holliday junctions promoted by the RuvA and RuvB proteins of E. coli. AB - The RuvA and RuvB proteins of E. coli, which are induced as part of the cellular response to DNA damage, act together to promote the branch migration of Holliday junctions. Addition of purified RuvA and RuvB to a RecA-mediated recombination reaction stimulates the rate of strand exchange and the formation of hetero duplex DNA. Stimulation does not occur via interaction with RecA; instead, RuvA and RuvB act directly upon recombination intermediates (Holliday junctions) made by RecA. We show that RuvAB-mediated branch migration requires ATP and can bypass UV-induced DNA lesions. At high RuvB concentrations, the requirement for RuvA is overcome, indicating that the RuvB ATPase provides the motor force for branch migration. RuvA protein provides specificity by binding to the Holliday junction, thereby reducing the requirement for RuvB by 50-fold. The newly discovered biochemical properties of RuvA, RuvB, and RuvC are incorporated into a model for the postreplicational repair of DNA following UV irradiation. PMID- 1617729 TI - The Drosophila homolog of the immunoglobulin recombination signal-binding protein regulates peripheral nervous system development. AB - The J kappa RBP binds to the immunoglobulin recombination signal sequence flanking the kappa-type J segment. We previously isolated the highly conserved homolog of the J kappa RBP gene from D. melanogaster, which is not thought to have immunoglobulin molecules. Using many deficiency mutants and in situ hybridization, we mapped the Drosophila J kappa RBP gene in a region containing two recessive lethal mutations, i.e., br26 and br7, which shows the dominant Suppressor of Hairless (Su(H)) phenotype in heterozygotes. All six Su(H) alleles analyzed at the DNA level contained mutations in the Drosophila J kappa RBP gene. Since the Su(H) mutation affects peripheral nervous system development, the Drosophila J kappa RBP gene product is involved in gene regulation of peripheral nervous system development. The results also imply that the immunoglobulin recombination signal sequence and the target sequence of the Drosophila J kappa RBP protein might have a common evolutionary origin. PMID- 1617730 TI - Suppressor of Hairless, the Drosophila homolog of the mouse recombination signal binding protein gene, controls sensory organ cell fates. AB - Suppressor of Hairless (Su(H)) is required at two stages of adult sensory organ development in Drosophila. Complete loss of Su(H) function results in a "neurogenic" phenotype in imaginal discs, in which too many cells adopt the sensory organ precursor cell fate. Su(H) is also involved in controlling the fates of sensillum accessory cells and is specifically expressed in two of these cells. Su(H) is the Drosophila homolog of the mouse J kappa RBP gene, whose product binds specifically to the recombination signal sequence of immunoglobulin J kappa segments. The Su(H) and J kappa RBP proteins are 82% identical over most of their length, and share with bacteriophage integrates and yeast recombinases a motif that includes residues directly involved in catalyzing recombination. PMID- 1617731 TI - A reticulocyte-binding protein complex of Plasmodium vivax merozoites. AB - Plasmodium vivax merozoites primarily invade reticulocytes. The basis of this restricted host cell preference has been debated. Here we introduce two novel P. vivax proteins that comigrate on reducing SDS-polyacrylamide gels, colocalize at the apical pole of merozoites, and adhere specifically to reticulocytes. The genes encoding these proteins, P. vivax reticulocyte-binding proteins 1 and 2 (PvRBP-1 and PvRBP-2), have been cloned and analyzed. Homologous genes are evident in the closely related simian malaria parasite, P. cynomolgi, which also prefers to invade reticulocytes, but are not evident in the genome of another related simian malaria parasite, P. knowlesi, which invades all red blood cell subpopulations. Native PvRBP-1 is likely a transmembrane-anchored disulfide linked protein, and along with PvRBP-2 may function as an adhesive protein complex. We propose that the RBPs of P. vivax, and homologous proteins of P. cynomolgi, function to target the reticulocyte subpopulation of red blood cells for invasion. PMID- 1617733 TI - Transformation of Aspergillus flavus: construction of urate oxidase-deficient mutants by gene disruption. AB - A transformation procedure based on the complementation of a genetic defect was developed using a nitrate reductase-deficient mutant of Aspergillus flavus. The initial transformation efficiency was improved 40-fold by combining factors in a planned experimental program. Although low, this transformation rate was sufficient to obtain transformants in which the urate oxidase-encoding gene (uaZ) was disrupted in a gene replacement experiment. These new uaZ- strains were unable to utilize uric acid as the unique nitrogen source and could be reversed directly to the wild-type phenotype in second order transformation experiments using a urate oxidase-expressing vector. PMID- 1617732 TI - Multiple copies of SUC4 regulatory regions may cause partial de-repression of invertase synthesis in Saccharomyces cerevisiae. AB - Transformation to generate multiple copies of regulatory DNA sequences has been used to study the interactions between regulatory proteins and their target sequences, since a high copy number of these sequences may titrate trans-acting regulatory proteins. We have analyzed the synthesis of invertase in yeast strains carrying different SUC genes transformed with the multiple-copy plasmid pSH143, a derivative of pJDB207 containing the promoter and upstream regulatory sequences of SUC4. The results obtained seem to be strain dependent. Under repressing conditions a high copy number of SUC4 promoter regions may cause increased expression of the invertase genes resulting in the synthesis of external glycosylated protein. A similar result was obtained under de-repressing conditions since transformants from some strains showed higher levels of activity. These results suggest that transcriptional regulatory (negative) factors may become limiting when the copy number of their target DNA sequences is increased. This effect may depend on the amount of active repressor molecules as well as on their affinity for SUC4 upstream sequences. This is discussed on the basis of the nucleotide sequences of SUC promoters. PMID- 1617735 TI - High efficiency transformation of Fusarium solani f. sp. cucurbitae race 2 (mating population V). AB - A cosmid vector, suitable for library construction and DNA transformation in filamentous fungi, has been constructed and a reliable and highly efficient PEG mediated DNA transformation system for F. solani f. sp. cucurbitae, based on resistance to hygromycin B, has been developed for use with this vector. This transformation system yielded 10(4) transformants per micrograms of DNA when using 10(7) protoplasts. Factors important in achieving high efficiency included: the maintenance of an osmoticum in all transformation steps, PEG 4000 concentration, and the ratio of transforming vector DNA to protoplasts. Approximately 60% of transformants stably integrated vector DNA. Molecular analysis revealed multiple copies of the plasmid integrated into the genome at one or more sites. The frequency of transformation achieved will facilitate the isolation of genes from this fungus by complementation. PMID- 1617734 TI - Cloning and mutation of the gene encoding endothiapepsin from Cryphonectria parasitica. AB - Endothiapepsin is an aspartic protease secreted by Cryphonectria parasitica. It has a milk-clotting activity and is used in the cheese industry. The eapA gene encoding endothiapepsin has been cloned and sequenced. An open reading frame of 419 codons, which encodes a precursor differing from mature endothiapepsin by the presence of an 89 aa residue prepro-sequence, was found. The eapA gene is interrupted by three introns. C. parasitica mutant strains deficient in the production of endothiapepsin (eapA-) were constructed using a gene-replacement strategy. Two nonsense mutations were introduced at the beginning of the coding sequence by PCR-induced mutagenesis. The mutated DNA fragment was introduced in C. parasitica by co-transformation with a benomyl-resistant (benR) selection plasmid. Transformants which have the eapA- phenotype were obtained. Protein analysis confirmed that they secreted no detectable amount of endothiapepsin. No ectopic integration of the mutated eapA gene occurred in the eapA- transformants. Moreover, after one conidiation step, eapA- transformants yielded benomyl sensitive (benS) segregants which were analyzed by Southern blotting experiments. The results revealed no difference with the wild-type strain, suggesting that the eapA-, benS segregants differed from the non-transformed strain only by the presence of the two nonsense mutations in the eapA locus. PMID- 1617736 TI - Electrophoretic karyotyping of wild-type and mutant Trichoderma longibrachiatum (reesei) strains. AB - An electrophoretic karyotype of Trichoderma longibrachiatum (reesei) was obtained using contour-clamped homogeneous electric field (CHEF) gel electrophoresis. Seven chromosomal DNA bands were separated in the wild-type T. longibrachiatum strain QM6a. The sizes of the chromosomal DNA bands ranged from 2.8 to 6.9 Mb, giving an estimated total genome size of about 33 Mb. The electrophoretic karyotype of the strain QM6a was compared to three hyper-celluloytic mutant strains, QM9414, RutC30 and VTT-D-79125. The chromosome pattern of the mutant QM9414 was quite similar to that of the wild-type QM6a except that the smallest chromosome differed somewhat in size. The VTT-D-79125 and RutC30 strains, which have undergone several mutagenesis steps, showed striking differences in their karyotype compared to the initial parent. The chromosomal DNA bands were identified using the previously characterized T. longibrachiatum genes (egl1, egl2, cbh1, cbh2, pgk1, rDNA) and random clones isolated from a genomic library. In all strains the cellulase genes cbh1, cbh2 and egl2 were located in the same linkage group (chromosome II in the wild-type), while the main endoglucanase, egl1, hybridized to another chromosomal DNA band (chromosome VI in the wild type). PMID- 1617737 TI - Suppression of cytoplasmic senescence in Neurospora. AB - We have shown that senescence in Kalilo strains of Neurospora, caused by a linear mitochondrial plasmid called kalDNA, is suppressible by existing variants of the nuclear genome. The suppressors are manifested by 4:4 segregation of senescence and immortality in asci from crosses between senescent female strains and males chosen from non-senescent candidate stocks. In one case of suppression, the asci also show segregation at the plasmid level. There is a reduction of kalDNA to barely detectable levels in the four ascospores showing immortality, so this suppressor evidently influences the maintenance of the plasmid itself. In the other case of suppression, the phenotypic segregation is not correlated with segregation at the plasmid level, and all eight ascospores in the asci show both free and inserted forms of kalDNA. This suggests that the suppression genotype provides a way of tolerating the presence of the plasmid rather than diminishing it. However, the allele f, which provides an analogous kind of suppression for the cytoplasmic mutation poky, does not suppress Kalilo or Maranhar senescence. Suppression is hence shown to be a possible option for host strains to combat the plasmid in nature, but no examples of suppressors were found in a limited survey of natural isolates. In addition, we have shown that long-lived, presumably non senescent, strains do not arise by suppressor mutation, but lose senescence plasmid DNA by another mechanism. PMID- 1617738 TI - Chloroplast RNA polymerase genes of Chlamydomonas reinhardtii exhibit an unusual structure and arrangement. AB - Nucleotide sequence analysis of a 17043 base-pair (bp) region of the Chlamydomonas reinhardtii plastome indicates the presence of three open reading frames (ORFs) similar to RNA polymerase subunit genes. Two, termed rpoB1 and rpoB2, are homologous to the 5'- and 3'-halves of the Escherichia coli beta subunit gene, respectively. A third, termed rpoC2, is similar to the 3'-half of the bacterial beta' subunit gene. These genes exhibit several unusual features: (1) all three represent chimeric structures in which RNA polymerase gene sequences are juxtaposed in-frame with long sequences of unknown identity; (2) unlike their counterparts in plants and eubacteria, rpoB1 and rpoB2 are separated from rpoC2 by a long (7 kilobase-pair, kbp) region containing genes unrelated to RNA polymerase; (3) DNA homologous to the 5' half of rpoC (termed rpoC1 in other species) is not present at the 5' end of rpoC2 and could not be detected in C. reinhardtii chloroplast DNA. RNA expression could not be detected for any of the RNA polymerase genes, suggesting that they are pseudogenes or genes expressed at stages of the C. reinhardtii life-cycle not investigated. The three genes are flanked by GC-rich repeat elements. We suggest that repeat DNA-mediated chloroplast recombination events may have contributed to their unusual arrangement. PMID- 1617739 TI - Co-transcription of orf25 and coxIII in rice mitochondria. AB - Southern hybridization analysis using homologous maize probes indicated that orf25 and coxIII are closely linked in the mitochondrial genome of rice (Oryza sativa) cultivar IR36. The two coding regions were found on the same 5.1 kb BamHI fragment, and this fragment was cloned, mapped and partially sequenced. Using probes for each gene derived from the rice clone, a 2.4 kb dicistronic mRNA transcript was found containing both orf25 and coxIII coding regions. Multiple 5' ends were identified by primer extension analysis and a double stem/loop structure was mapped to the 3' end. The orf25 coding region shares greater than 85% identity with orf25 sequences from maize, tobacco and wheat, suggesting that orf25 may code for a conserved protein product. PMID- 1617740 TI - Nuclear genes control changes in the organization of the mitochondrial genome in tissue cultures derived from immature embryos of wheat. AB - Although the mitochondrial genomes of the Chinese Spring and Aquila varieties of wheat are normally similar in organization, this is not so in tissue cultures initiated from their immature embryos where the mitochondrial genomes of both are rearranged and in different, characteristic, ways. However, the mitochondrial genomes of tissue cultures of reciprocal F1 crosses between these varieties were almost identical to one another, showing that nuclear genes control the rearrangement processes. These rearrangements are either due to the appearance of new structures or else result from changes in the relative amounts of subgenomic components. The severe reduction in the amount of certain molecular configurations in tissue cultures from reciprocal crosses is probably due to the presence of dominant information in the Aquila nuclear genome. Data obtained from tissue cultures initiated from F2 embryos of the cross Aquila x Chinese Spring suggest that at least two complementary genes are involved in this control. In contrast, the presence of new molecular arrangements appears to be under the control of a dominant allelic form of a Chinese Spring gene or genes. Thus, this study demonstrates that at least two sets of nuclear genes control the reorganization of the mitochondrial genome which occurs when tissue cultures are initiated from the immature embryos of wheat. PMID- 1617742 TI - [Pathological analysis of sudden coronary death in 31 autoptic cases]. AB - 31 cases of sudden coronary death (within 1 hour, unexpected death) in 160 autoptic cases of coronary heart disease were studied (19.4%), including 24 male and 7 female; age 16-79, average 59.5. Most cases of sudden death had no obvious inductive causes. 18 patients died without cardiac symptoms, including those died before admission or during deep sleep. There was atherosclerotic stenosis (grade 4), of the coronary artery in 25 cases, of which 18 cases were with multiple branches involvement (grade 4) and 7 cases were with simple branch damage. Myocardial infarction was found in 24 cases, and myocardial ischemia in 7 cases. Old myocardial infarction was seen in 14 cases, and it was combined with acute myocardial infarction in 8 cases. Simple acute myocardial infarction was only seen in 2 cases. 8 cases showed ventricular aneurysm and 1 patient died of cardiac rupture. Conclusively, severe coronary stenosis and myocardial infarction are considered as one of the important bases of sudden coronary death. PMID- 1617741 TI - Organization and structure of plastome psbF, psbL, petG and ORF712 genes in Chlamydomonas reinhardtii. AB - We have determined the nucleotide sequence of a 5159 base-pair (bp) region of the Chlamydomonas reinhardtii plastome containing three photoelectron transport genes, psbF, psbL and petG, and an unusual open reading frame, ORF712. The photosynthetic genes have an unprecedented arrangement, psbF and psbL are located in close proximity to petG, and are not grouped with two other genes of the cytochrome b559 locus, psbE and ORF42. ORF712, located adjacent to psbL, has homology at its 5'- and 3'-ends to the ribosomal protein rps3 gene, but contains a central 437 residue domain that lacks similarity to any other known sequence. These sequences add to the growing body of evidence that the chloroplast genome of C. reinhardtii has a significantly different gene arrangement to its counterpart in plants. The structure of ORF712 also provides another example of a phenomenon we have discovered with C. reinhardtii RNA polymerase genes (Fong and Surzycki 1992); namely, that the algal plastome contains chimeric genes in which reading frames with homology to known genes are juxtaposed in-frame with long coding regions of unknown identity. PMID- 1617743 TI - [The phenotype of mast cells in primary adenoid liver tumours of rats and its relation to tumor cells]. AB - Mast cells in adenoid liver tumours of 32 rats induced with nitrosomorpholine were observed ultrastructurally, and among them, some were studied immunocytochemically via immunogold techniques. Data indicated that mast cells which located in tumour tissues presented positive expression of rat mast cell protein (RMCP) II, indicating origination from the mucosal mast cells, while those in the connective tissues around tumours were largely stained negatively with either RMCP II or RMCP I antisera, with the exception of only a few cells showing positive RMCP II staining. Ultrastructural observation showed that mast cells in tumors contacted closely with the tumor cells. Membranes of the intracellular granules in these mast cells were fusing together. The content inside the granules were discharged and spread along the intercellular space between the tumor cells. There was not any lesion obtained ultrastructurally at the contacting point between the tumor cells and the mast cells. The significance of mucosal mast cells in adenoid liver tumors is briefly discussed. PMID- 1617744 TI - [Autopsy study of 100 elderly patients]. AB - Clinical and autopsy records of 100 elderly patients were analyzed. The most common cause of death in this series was malignant tumors (39%). The second leading cause of death was diseases of the circulatory system (37%), in which cerebrovascular accident alone accounted for 21%. Cor pulmonale and myocardial infarction were also common causes of death. In addition, infective diseases, especially pneumonia and septicemia were often fatal to elderly patients. The discrepancy between clinical and post-mortem diagnoses in this series was 24.7%. The causes of incorrect and missed diagnoses are discussed. The results suggest that extensive autoptic study still has vital practical significance. PMID- 1617745 TI - [Clinicopathological study on 3441 cases of benign and malignant ulcers. The National Cooperative Group for Pathological Study on the Canceration of Gastric Ulcer]. AB - Resected specimens of benign and malignant gastric ulcers from 3441 cases were studied and compared clinically and pathologically. Among them, 421 cases of malignant ulcer were found. The malignant ulcers differed notably from the ulcerating gastric carcinoma and showed many similarities to the benign chronic gastric ulcer (CGU). The most distinct feature of malignant ulcer was the lack of cancerous infiltration and muscular residue in the scar tissue of ulcer base. The existence of this type of ulcer clinically and pathomorphologically supports the viewpoint that CGU can undergo malignant change. The rate of malignant change of CGU in this study was 3.48%. PMID- 1617747 TI - [Three-dimensional microstructure and its significance of pseudotubular formation in the crescents of rapidly progressive glomerulonephritis]. AB - Tubuloid structure of the crescents in rapidly progressive glomerulonephritis (RPGN) was studied in order to detect its morphological features and functional significance by using three-dimensional microstructure method. The results showed that the tubuloid structure was actually pseudotubular formation in the crescents. Their inner lumens were communicating between the Bowman's capsular space and lumens of the renal tubules. It indicated that pseudotubular formation in the crescents may play an important role in repairing the damaged structure of those injured glomeruli. PMID- 1617746 TI - [Pathological study of malignant peripheral nerve sheath tumor in rat]. AB - Sequential morphological studies of rat malignant peripheral nerve sheath tumors induced with ethylnitrosourea were performed by light microscopy, transmission electron microscopy, scanning electron microscopy, immunohistochemistry and nude mice transplantation. The result indicated that rat malignant peripheral nerve sheath tumor was actually a sarcoma arising from Schwann cell within the peripheral nerve, which possesses some basic morphological characteristics as those of human malignant peripheral nerve sheath tumor, and is considered worthy to be used as a model for further studies. PMID- 1617748 TI - [Interaction of foamy cells from experimental hyperlipemia rabbits with smooth muscle cells and the endothelial surface of intima preparation]. AB - In the development of atherosclerosis (AS), circulating monocytes emigrate into and accumulate in the intima as foamy cells. Interaction of the lipid laden macrophage (M phi) with cells of the arterial wall may contribute to the formation of atheromatous plaque. Using subcutaneous and peritoneal foamy cells (FC) collected from diet-induced hyperlipemia rabbits, the authors observed the influence of lipid laden on macrophage's functions relevant to AS lesion formation. In comparison with normal M phi, peritoneal FC were 4.8 and 5.4 fold more adhesive to the endothelial surface of intima preparation and the smooth muscle cells (SMC), while the adhesion rate produced by subcutaneous FC were increased 0.79 and 0.16 fold. SMC migration stimulated by both FC-conditioned medium slowed 5.78 and 5.90 fold increased respectively as in comparing with the control's, whereas normal M phi-conditioned medium only gave a 2.3 fold increase of SMC migration stimulation. In addition, both FC-conditioned medium stimulated SMC growth making 1.96 and 2.59 fold increase, and normal M phi-conditioned medium produced a 1.3 fold increase as compared with the control's. The results suggest that lipid-laden macrophages, may accelerate AS development due to changes of their biological properties. Since more than 95% of peritoneal macrophages as well as macrophages in the pleura, pericardial and synovial cavities from experimental hyperlipidemia rabbits are fully filled with lipid assuming the morphologic characteristics of atheromatous intimal foamy cells, it is considered that these cells will be valuable as the model. PMID- 1617749 TI - [Value of monoclonal antibodies in the diagnosis of Hodgkin's disease in paraffin sections]. AB - A comprehensive panel of monoclonal antibodies that mark R-S/H cell, T- and B cell, monocyte/histocyte was tested in paraffin sections of 107 cases of Hodgkin's disease (HD) including 21 cases of lymphocyte predominance (LP) and 86 cases of Non-LP HD. Thirty cases each of peripheral T-cell lymphoma and B-cell lymphoma were also tested for comparison. R-S/H cells were not stained with T cell marker (UCHL-1) or monocyte/histocyte marker (Mac387) in all of these cases of HD. The results showed presence of certain difference in the phenotype of LP from non-LP. The H+L type of R-S/H cells of LP often reacted with B-cell markers including L26, LN2, LN1 and MB2 (93.3%-100%), LCA (83.3%) and EMA (92.3%), but rarely with LeuM1,T mu 9, or BerH2. On the contrary, most of the R-S/H cells of non-LP reacted with LeuM1 (80%), T mu 9(84%), BerH2(65%) but not with B-cell markers, LCA or EMA. Our study suggests a B-cell (probably the follicular center cell) derivation for L+H type of R-S/H cells in LP. The fact that 1 case of LP in this group transformed to a large cell B-cell lymphoma also supports this consideration. PNA is a sensitive marker of R-S/H cells but is not a specific one, since PNA stains 43.3% of the peripheral T-cell lymphoma and 20% of the B cell lymphomas. Our findings indicate that using a panel of antibodies which mark R-S/H cells, T- and B-cells in paraffin sections will be helpful in the diagnosis and subtyping of Hodgkin's disease. PMID- 1617750 TI - [The protective effect of apolipoprotein C1 on endothelial cells injured by low density lipoprotein in vitro]. AB - High serum low density lipoprotein (LDL) level is known injurious to endothelial cell (EC) and that high density lipoprotein (HDL) protects EC from such injury. The protective effect of HDL and apolipoprotein C1 (apo C1) on the endothelial cells (EC) isolated originally from human umbilical vein and injured by LDL was studied morphologically with phase-contrast and transmission electron microscope. Additionally, their functional changes were detected by measuring the amount of lactate dehydrogenase (LDH) and 6-keto-prostaglandin F1 alpha (PGF1 alpha) released. The EC were divided into four groups: control, HDL+LDL, apo C1 + IDL and LDL group. EC after being injured by LDL showed cell contraction, increased release of LDH and decreased secretion of PGF1. Anyhow, they would be left normal on morphology, LDH release and PGF1 alpha synthesis if HDL or apo C1 had been added to the culture media before LDL injury. The results indicated that both HDL and apo C1 can resist the injurious effect of LDL on the cultured EC. PMID- 1617751 TI - [Application of the centripetal nature rescue in the emergency department]. PMID- 1617753 TI - [Psycho-soma holistic care model for abdominal surgery]. PMID- 1617752 TI - [Survey of psychotic inpatients who refuse treatment]. PMID- 1617754 TI - [Using the hospital stress scale in nursing practice]. PMID- 1617756 TI - [Nursing care of children with head and neck cancer treated by radiotherapy]. PMID- 1617755 TI - [Changes in endocrine rhythm of nurses on night duty]. PMID- 1617757 TI - [Speech rehabilitation after cleft palate surgery]. PMID- 1617758 TI - The perception and use of child health clinics in a sample of working class families. AB - The frequency and pattern of clinic use by a sample of 60 working class families is described. An attempt is made to explain attendance and non-attendance in terms of the mothers' perceptions of the clinic's functions and relevance and in terms of certain social and organizational barriers. The implications of the findings for clinic use and for the organization and delivery of the service to working class families are discussed. PMID- 1617759 TI - The role of social support and stressors for mothers and infants. AB - This correlational study of mothers and their 6-month-old infants examined the importance of social support and stressors for parenting and infant development. Mothers (n = 79) were primarily White, married, and ranged in socio-economic status from low to high. All data were collected in mothers' homes when infants were 6 months old. Diversity of sources of social support and diversity of father support were positively related to parenting (quality of stimulation in the home). Diversity of sources of social support buffered the negative relationship of maternal fatigue (stressor) to parenting. Parenting was related to social, hearing-speech, locomotor, and general development. Additionally, social support and aggravation (people in the mother's said network who make life difficult) were related to infant development, independent of parenting. PMID- 1617760 TI - The school entry medical examination. What do teachers think of it? AB - Questionnaires were sent to 76 schools in the Macclesfield district. Seventy-four of these were returned by head teachers and/or reception teachers. Replies concerned the school entry medical examination, information on individual children, general health information and access to professionals. Additional comments on any aspects of the service were also solicited. The results have been analysed. The majority of teachers considered that the school entry medical examination is of value, but the quality of information reaching teachers is viewed more critically. Meetings were the most favoured means of communication, but there are obvious defects in the system. Some teachers did not even know of access channels. If improvements do not occur some of the value of the examination will be lost. Suggestions for better communications are made. With local management of schools, teacher opinion must be considered if a better school health service is to be provided for the children of the district. PMID- 1617761 TI - For discussion: a rethink on exploitation of young persons. PMID- 1617762 TI - Regular physical exercise and low-fat diet. Effects on progression of coronary artery disease. AB - BACKGROUND: Significant regression of coronary and femoral atherosclerotic lesions has been documented by angiographic studies using aggressive lipid lowering treatment. This study tested the applicability and effects of intensive physical exercise and low-fat diet on coronary morphology and myocardial perfusion in nonselected patients with stable angina pectoris. METHODS AND RESULTS: Patients were recruited after routine coronary angiography for stable angina pectoris; they were randomized to an intervention group (n = 56) and a control group on "usual care" (n = 57). Treatment comprised intensive physical exercise in group training sessions (minimum, 2 hr/wk), daily home exercise periods (20 min/d), and low-fat, low-cholesterol diet (American Heart Association recommendation, phase 3). No lipid-lowering agents were prescribed. After 12 months of participation, repeat coronary angiography was performed; relative and minimal diameter reductions of coronary lesions were measured by digital image processing. Change in myocardial perfusion was assessed by 201Tl scintigraphy. In patients participating in the intervention group, body weight decreased by 5% (p less than 0.001), total cholesterol by 10% (p less than 0.001), and triglycerides by 24% (p less than 0.001); high density lipoproteins increased by 3% (p = NS). Physical work capacity improved by 23% (p less than 0.0001), and myocardial oxygen consumption, as estimated from maximal rate-pressure product, by 10% (p less than 0.05). Stress-induced myocardial ischemia decreased concurrently, indicating improvement of myocardial perfusion. Based on minimal lesion diameter, progression of coronary lesions was noted in nine patients (23%), no change in 18 patients (45%), and regression in 13 patients (32%). In the control group, metabolic and hemodynamic variables remained essentially unchanged, whereas progression of coronary lesions was noted in 25 patients (48%), no change in 18 patients (35%), and regression in nine patients (17%). These changes were significantly different from the intervention group (p less than 0.05). CONCLUSIONS: In patients participating in regular physical exercise and low-fat diet, coronary artery disease progresses at a slower pace compared with a control group on usual care. PMID- 1617763 TI - Recombinant tissue-type plasminogen activator and immediate angioplasty in acute myocardial infarction. One-year follow-up. The European Cooperative Study Group. AB - BACKGROUND: The European Cooperative Study Group conducted two randomized trials in patients with suspected myocardial infarction to assess the effect of 100 mg single-chain recombinant tissue-type plasminogen activator (rt-PA, alteplase) on enzymatic infarct size, left ventricular function, morbidity and mortality relative to placebo (alteplase/placebo trial) and to assess the effect of immediate percutaneous transluminal coronary angioplasty (PTCA) in addition to alteplase (alteplase/PTCA trial). One-year follow-up results are reported. METHODS AND RESULTS: In the alteplase/placebo trial, 721 patients with chest pain of less than 5 hours and extensive ST-segment elevation were allocated at random to 100 mg alteplase or placebo (double-blind) over 3 hours. In the alteplase/PTCA trial, 367 similar patients received alteplase and subsequently were allocated at random to immediate coronary angiography and angioplasty of the infarct-related vessel or control. All patients received aspirin and intravenous heparin. In the alteplase/placebo trial, mortality during the first year was reduced by 36% with alteplase (from 9.3% to 5.6%; difference, -3.7%; 95% confidence interval, -7.5% to 0.2%). Revascularization was performed more frequently after alteplase, and more patients in the alteplase group were in New York Heart Association functional class I or II. Reinfarction tended to occur more frequently after alteplase than after placebo. In the alteplase/PTCA trial, reinfarction was less common after immediate PTCA, and revascularization procedures were less frequent. However, this benefit was offset by a high rate of immediate reocclusion and early recurrent ischemia and by higher mortality at 1 year (9.3% versus 5.4%; difference, 3.9%; 95% confidence interval, -1.5% to 9.2%) in the invasive group. In a multivariate analysis of 1,043 hospital survivors, mortality after discharge was related to coronary anatomy, left ventricular function, age, and previous infarction but not to initial treatment allocation. Reinfarction after hospital discharge tended to be more common after alteplase and related to coronary anatomy. CONCLUSIONS: Benefit from treatment with alteplase, heparin, and aspirin is not diminished at 1 year. Routine immediate PTCA does not confer additional benefit. Prognosis after hospital discharge mainly is determined by coronary anatomy and residual left ventricular function and is unrelated to initial treatment assignment. PMID- 1617764 TI - Pathogenesis of congestive state in chronic obstructive pulmonary disease. Studies of body water and sodium, renal function, hemodynamics, and plasma hormones during edema and after recovery. AB - BACKGROUND: The pathogenesis of salt and water accumulation in patients with chronic obstructive pulmonary disease is unclear and may differ from that in patients with congestive heart failure due to myocardial disease. This study was undertaken to investigate some of the mechanisms involved. METHODS AND RESULTS: Hemodynamics, water and electrolyte spaces, renal function, and plasma hormone concentrations were measured in nine patients with edema due to chronic obstructive pulmonary disease and in six patients after recovery. Mean cardiac output (3.8 +/- 0.26 l/min.m2) was normal, but right atrial (11 +/- 1 mm Hg) and mean pulmonary arterial (41 +/- 3 mm Hg) pressures were increased. Mean pulmonary arterial wedge pressure (11 +/- 1 mm Hg) was normal. Pulmonary vascular resistance (8.6 +/- 1.3 mm Hg.min.m2/l) was increased, but systemic vascular resistance (19.3 +/- 1.3 mm Hg.min.m2/l) and mean arterial pressure (83 +/- 4 mm Hg) were low. All patients were hypoxemic (PaO2, 40 +/- 2 mm Hg) and hypercapnic (PaCO2, 60 +/- 2 mm Hg). There was a significant increase in total body water (+21%), extracellular volume (+45%), plasma volume (+45%), blood volume (+88%), and exchangeable sodium (+38.2%). Renal plasma flow was severely reduced ( 63.2%), but glomerular filtration rate was only mildly decreased (-32%). Significant increases were seen in plasma norepinephrine (3.5-fold normal), renin activity (7.6-fold normal), vasopressin (twice normal), atrial natriuretic peptide (9.4-fold normal), growth hormone (10.7-fold normal), and cortisol (1.9 fold normal). After recovery, the PaO2 increased (50 +/- 3 mm Hg) and PaCO2 fell (45 +/- 4 mm Hg), and the patients became free from edema. All the body compartments returned toward normal, although they did not entirely reach normal values. Renal plasma flow increased significantly, and glomerular filtration became normal. Right atrial and pulmonary arterial pressures and pulmonary vascular resistance decreased (p less than 0.01). Cardiac output decreased but not significantly. Blood pressure increased but not significantly. However, systemic vascular resistance increased significantly to a normal value. CONCLUSIONS: We conclude that patients with edema due to chronic obstructive pulmonary disease have severe retention of salt and water, reduction in renal blood flow and glomerular filtration, and neurohormonal activation similar to that seen in patients with edema due to myocardial disease. However, unlike the latter, in chronic obstructive pulmonary disease cardiac output is normal, and systemic vascular resistance and arterial blood pressure are low. This probably is due to the vasodilator properties of hypercapnia. The consequent low arterial blood pressure may be the stimulus for the neurohormonal activation and retention of salt and water. PMID- 1617765 TI - Eighteen-year follow-up in the Veterans Affairs Cooperative Study of Coronary Artery Bypass Surgery for stable angina. AB - BACKGROUND: The 18-year effect of bypass surgery compared with medical therapy on survival, incidence of myocardial infarction, and relief of angina was evaluated in 686 randomized patients with stable angina in the Veterans Affairs Cooperative Study of Coronary Artery Bypass Surgery. METHODS AND RESULTS: The primary treatment comparisons were made according to intent to treat; 44% of the entire medical cohort had bypass surgery during a median follow-up of 16.8 years. Overall 18-year survival rates were 33% for medicine compared with 30% for surgery (p = 0.60). Survival rates for high-risk patients without left main disease, which had shown a significant advantage for surgical therapy up to 11 years, were 23% medicine versus 24% surgery for patients with three-vessel disease and impaired left ventricular function (p = 0.49) and 22% versus 25% for those with multiple clinical risk factors (p = 0.12). For patients with two vessel disease, who had significantly better survival with medical therapy at 11 years, rates were similar at 18 years in the two treatment groups (34% medicine versus 30% surgery, p = 0.09). Cumulative 18-year myocardial infarction rates (fatal plus nonfatal) were 41% in medical and 49% in surgical patients (13% perioperative infarction rate), p = 0.15. Nonfatal infarction rates were lower with medical than with surgical therapy (32% versus 44%, p = 0.015), but fatal infarction rates were similar (14% medicine versus 13% surgery, p = 0.62). The combined rate of myocardial infarction or death was also lower with medical therapy (75% versus 82%, p = 0.016). In contrast, surgery reduced mortality after myocardial infarction by 35% at 10 years (p less than 0.001) but only by 13% at 18 years (p = 0.09). The percent of medical and surgical patients who were angina free was 3% versus 22% (p less than 0.001) at 1 year and 4% versus 12% (p less than 0.001) at 5 years compared with rates of 6% versus 5% (p greater than 0.50) at 10 years and 3% versus 4% (p greater than 0.50) at 15 years. CONCLUSIONS: The benefits of coronary artery bypass surgery on survival, symptoms, and postinfarction mortality were transient and lasted fewer than 11 years. The benefits began to diminish after 5 years, when graft closure accelerated. Surgery was effective in reducing mortality only for patients with a poor natural history. Low-risk patients, who had a good prognosis with medical therapy, derived no survival benefit with surgical therapy at any time during the follow up period. Regardless of risk, surgery also did not reduce the incidence of myocardial infarction or the combined incidence of infarction or death. PMID- 1617766 TI - Thrombolysis in patients with unstable angina improves the angiographic but not the clinical outcome. Results of UNASEM, a multicenter, randomized, placebo controlled, clinical trial with anistreplase. AB - BACKGROUND: The value of thrombolytic therapy in unstable angina is unclear. METHODS AND RESULTS: To study this problem, 159 patients were studied in a double blind, placebo-controlled multicenter trial. Patients without a previous myocardial infarction, with a typical history of unstable angina, and ECG abnormalities indicative of ischemia were included. After baseline angiography, study medication (anistreplase or placebo) was given. Angiography was repeated after 12-28 hours. A significant decrease occurred in diameter stenosis between the first and second angiogram in the anistreplase group compared with the placebo group (11% versus 3%, p = 0.008). This difference was caused by reopening of occluded vessels in the thrombolytic group. However, no beneficial clinical effects of thrombolytic treatment were found. Bleeding complications were significantly higher in patients who received thrombolytic therapy (21 versus seven patients, p = 0.001). CONCLUSIONS: Thus, angiographic but no clinical improvement after thrombolytic treatment with anistreplase was found in patients with unstable angina with an excess of bleeding complications. Therefore, thrombolytic treatment cannot be recommended in patients diagnosed as having unstable angina until proven otherwise. PMID- 1617767 TI - Expression and localization of dystrophin in human cardiac Purkinje fibers. AB - BACKGROUND: Mutations in the dystrophin gene produce clinical manifestations of disease in heart, brain, and skeletal muscle in patients with Duchenne and Beckers muscular dystrophy (DMD/BMD). Conduction disturbances and heart block contribute to cardiac decompensation in these patients, which suggests an important role for dystrophia in the cardiac conduction system. We therefore examined the messenger RNA (mRNA) expression and protein localization of dystrophin in normal human cardiac Purkinje fibers. METHODS AND RESULTS: Polymerase chain reaction amplification of isolated Purkinje fiber complementary DNA identified several alternatively spliced mRNA transcripts encoding for carboxy-terminal isoforms of the dystrophin protein. The predominant mRNA transcript detected was a splice form previously detected in the brain. Antipeptide antibodies specific for a carboxy-terminal dystrophin sequence were used for Western blot analysis and immunocytochemical localization. These antisera detect approximately 400,000-d immunoreactive band or bands on Western blot in normal heart and Purkinje fibers but not in DMD heart. Immunocytochemical staining showed that dystrophin was localized to the membrane surface of the Purkinje fiber. CONCLUSIONS: These results suggest that dystrophin may be an important molecule for membrane function in the Purkinje conduction system of the heart and support the hypothesis that defective dystrophin expression contributes to the cardiac conduction disturbances seen in DMD/BMD: PMID- 1617768 TI - Intravascular ultrasound imaging of coronary arteries. Is three layers the norm? AB - BACKGROUND: The purpose of this study was to evaluate the significance of the three-layered appearance of coronary arteries in adolescence and adults from intravascular ultrasound scans and to correlate these observations with histopathology. METHODS AND RESULTS: Sixteen intact hearts were excised at autopsy from patients with no clinical history of coronary artery disease. The patients' ages ranged from 13 to 55 years. A 30-MHz ultrasound imaging catheter was used to obtain images throughout the epicardial coronary vasculature. A total of 72 image cross sections was marked by epivascular sutures, and the corresponding histological sections were examined. Ultrasound images were classified into two groups: images exhibiting three-layered appearance and images without distinct layering. Histological analysis revealed a significantly greater degree of intimal thickening in segments with three layers (243 +/- 105 microns) than in nonlayered segments (112 +/- 55 microns). Discriminant analysis of these data predicted the threshold between the two groups to be 178 microns. Measurements of medial thickness were not different between these two groups (235 +/- 61 versus 210 +/- 76 microns). In the nonlayered group, the average patient age was 27.1 +/- 8.5 years, whereas in the three-layered groups, the average age was 42.8 +/- 9.8 years. CONCLUSIONS: The intracoronary ultrasound image appearance of young, morphologically normal coronary artery walls is homogeneous without layering. A three-layered appearance suggests the presence of at least 178 microns of intimal thickening and is seen more frequently with advancing age. PMID- 1617769 TI - Estimation of left ventricular cavity area with an on-line, semiautomated echocardiographic edge detection system. AB - BACKGROUND: Automated edge detection of endocardial borders in echocardiograms provides objective, reproducible estimation of cavity area; however, most methods have required off-line analysis. A recently developed prototype echocardiographic imaging system permits real-time automated edge detection during imaging and thus, the potential for measurement of cyclic changes in cavity area and the assessment of left ventricular function on-line. Our purpose was to compare measurements of endocardial area manually traced from conventional echocardiograms with those obtained with the real-time automated edge detection system in normal subjects. METHODS AND RESULTS: Two training sets of images were used to establish optimal methods of gain setting; the settings were then evaluated in a test set of images. In the high-gain training group (n = 8 subjects, 119 images), gain settings were adjusted sufficiently high to display at least 90% of the endocardial border. Manually drawn and real-time area measurements correlated at r = 0.92, but manually drawn areas were underestimated by computer. In the low-gain training group (n = 7 subjects, 104 images), gain settings were adjusted sufficiently low to avoid cavity clutter despite the presence of dropout of endocardial edges. Manually drawn and real-time areas again correlated (r = 0.79), but manually drawn areas were overestimated by computer. In the intermediate-gain test group (n = 7 subjects, 105 images), gain settings were balanced between maximal endocardial definition (greater than or equal to 90%) and minimal cavity clutter (less than or equal to 1 cm2). Manually drawn and real-time areas correlated at r = 0.91 for the group, and r ranged from 0.94 to 0.99 in individual subjects. Interobserver variability was 9.5% for manually traced areas and 10.6% for real-time area measurements. CONCLUSIONS: Real-time on-line automated edge detection provides accurate estimation of manually drawn cavity areas. Although the method is gain dependent, measurements are reproducible. The system should have clinical application in settings in which measurements of left ventricular function are important. PMID- 1617770 TI - A new strategy for the assessment of viable myocardium and regional myocardial blood flow using 15O-water and dynamic positron emission tomography. AB - BACKGROUND: We have developed a new measure of myocardial viability, the water perfusable tissue index (PTI), which is calculated from transmission, C15O, and H2(15)O positron emission tomography (PET) data sets. It is defined as the proportion of the total anatomical tissue within a given region of interest (ROI) that is capable of rapidly exchanging water and has units g (perfusable tissue)/g (total anatomical tissue). The aim of this study was to assess the prognostic value of PTI in predicting improvement in regional wall motion after successful thrombolysis for acute myocardial infarction (AMI) and to measure the myocardial blood flow to the perfusable tissue (MBFp, ml/min/g [perfusable tissue]). Furthermore, PTI was compared with 18FDG metabolic imaging in patients with old myocardial infarction (OMI). METHODS AND RESULTS: PET scans were performed in healthy volunteers (group 1, n = 8), patients with OMI (group 2, n = 15), and in patients who were successfully thrombolysed after an AMI (group 3, n = 11). Systolic wall thickening was measured by two-dimensional echocardiography within 2-4 days of AMI and after 4 months to assess contractile recovery. In the healthy volunteers, MBFp was 0.95 +/- 0.13 ml/min/g (perfusable tissue). PTI in these regions was 1.08 +/- 0.07 g (perfusable tissue)/g (total anatomical tissue), which was consistent with all normal myocardium being perfusable by water. In the OMI group, the ratio of the relative 18FDG activity to the relative MBFp defect (metabolism-flow ratio) was calculated for each asynergic segment. Regions in which the metabolism-flow ratio was greater than or equal to 1.20 were considered reversibly injured, whereas those in which the ratio was less than 1.20 were deemed irreversibly injured. PTI in the former group of regions (n = 9) was 0.75 +/- 0.14 g (perfusable tissue)/g (total anatomical tissue) and was significantly higher than in irreversibly injured regions (n = 6) (0.53 +/- 0.12 g [perfusable tissue]/g [total anatomical tissue], p less than 0.01). Values of MBFp were similar in these segments. Seven of 12 segments in the AMI patients showed improved systolic wall thickening on follow-up. PTI in these recovery segments was 0.88 +/- 0.10 g (perfusable tissue)/g (total anatomical tissue) (p = NS versus control). PTI in the nonrecovery regions was 0.53 +/- 0.11 g (perfusable tissue)/g (total anatomical tissue), which was similar to the segments in group 2 in which 18FDG uptake was absent. MBFp was similar in both the recovery and nonrecovery segments in the subacute phase. CONCLUSIONS: These data indicate that PTI may be a good prognostic indicator for the recovery of contractile function after successful thrombolysis and show that myocardial viability may be assessed by PET without metabolic imaging. PMID- 1617771 TI - Coronary reserve and exercise ECG in patients with chest pain and normal coronary angiograms. AB - BACKGROUND: Coronary vasodilator reserve is reduced in some patients with a history of chest pain and angiographically normal coronary arteries. ECG changes suggestive of myocardial ischemia during exercise also can be demonstrated in a subset of these patients. METHODS AND RESULTS: We have investigated the correlation between coronary vasodilator reserve, assessed with 13N-labeled ammonia and positron emission tomography, and the ECG during exercise stress in 45 patients with a history of chest pain, angiographically normal coronary arteries, and a negative ergonovine test. ST segment depression on the ECG during exercise was present in 29 of 45 patients. Mean resting left ventricular blood flow was 1.04 +/- 0.22 ml.min-1.g-1; it increased to 1.32 +/- 0.47 ml.min-1.g-1 (p less than 0.01 versus baseline value) during atrial pacing and to 2.52 +/- 0.96 ml.min-1.g-1 (p less than 0.01 versus baseline value) after dipyridamole (0.56 mg/kg i.v.). No regional flow defects could be demonstrated in any patient during pacing or after dipyridamole. Myocardial flows after dipyridamole, however, did not show a normal frequency distribution (Kolmogorov-Smirnov test), and two patient populations could be identified. Twenty-nine (67%) patients had a mean left ventricular flow of 3.02 +/- 0.33 ml.min-1.g-1 after dipyridamole (range, 2.13-5.46 ml.min-1.g-1), and 14 (33%) patients had a mean flow of 1.48 +/ 0.29 ml.min-1.g-1 (range, 1.06-2.04 ml.min-1.g-1, p less than 0.01 versus the "high-flow group"). CONCLUSIONS: Approximately one third of patients in our series showed a reduced coronary vasodilator reserve. Although 12 of 14 patients in the "low-flow group" had ST segment depression during exercise stress, 16 of 29 patients in the high-flow group also had ST segment depression during exercise stress. Therefore, despite a good sensitivity (86%) in identifying patients with a blunted increment of coronary flow, the ECG response during exercise stress appears to have a rather low specificity (45%). This suggests that factors other than reduced coronary reserve and myocardial ischemia may play a role in the genesis of the ST segment depression in these patients. PMID- 1617772 TI - Effect of ketanserin on proximal and distal coronary constrictor responses to intracoronary infusion of serotonin in patients with stable angina, patients with variant angina, and control patients. AB - BACKGROUND: Serotonin, released by aggregating platelets, may contribute to or cause myocardial ischemia by constricting epicardial vessels. Experimental studies suggest that this constriction is mediated by two distinct serotonin receptor subtypes: 5-hydroxytryptamine1-like (S1-like) and 5-hydroxytryptamine2 (S2). METHODS AND RESULTS: To determine the relative contribution of S1-like and S2 receptors to the vasoconstrictor effects of serotonin, we studied the effect of ketanserin (0.75 mg, intracoronary), a selective S2 receptor antagonist, on the constrictor response of human coronary vessels to intracoronary infusions of serotonin. In control patients (n = 7), serotonin (10(-4) mol/l) caused significant (p less than 0.05) constriction only in distal segments, which was significantly (p less than 0.05) inhibited by ketanserin. In stable angina patients (n = 8), serotonin (10(-4) mol/l) caused significant constriction in proximal (p less than 0.01) and distal (p less than 0.01) segments, which was significantly inhibited by ketanserin in proximal (p less than 0.05) but not distal (p = 0.30) segments. In patients with variant angina (n = 3), epicardial occlusion at the site of preexisting stenoses in proximal locations occurred at infused concentrations of 10(-6) (one patient) or 10(-5) (two patients) mol/l. The infusion of the same concentration of serotonin after ketanserin again caused epicardial occlusion. CONCLUSIONS: Our results suggest that functionally important S1-like receptors that mediate vasoconstriction exist in the epicardial vessels of patients with stable or variant angina. Their activation, either at hyperreactive sites in patients with variant angina or in the distal epicardial vessels of patients with chronic stable angina, may contribute to or cause myocardial ischemia when serotonin is released after the intracoronary activation of platelets. PMID- 1617773 TI - Hemodynamic evaluation before and after closure of fenestrated Fontan. An acute study of changes in oxygen delivery. AB - BACKGROUND: Acute changes in hemodynamics and oxygen delivery accompanying temporary occlusion of atrial defects in 14 patients after a fenestrated Fontan procedure were evaluated at a median interval of 32 days after surgery to identify candidates for permanent transcatheter closure of their defects. METHODS AND RESULTS: Patients ranged in age from 9 months to 33 years and in weight from 7.9 to 69 kg. Right atrial (RA), left atrial (LA), and aortic pressures, mixed venous (SmvO2) and aortic (SaO2) oxygen saturation, and whole-body oxygen consumption (VO2) were measured, and systemic blood flow (Qs), systemic oxygen transport (SOT), and oxygen extraction were calculated before and after occlusion. SmvO2, VO2, and RA pressures did not change, but SaO2 increased from 84 +/- 6% to 95 +/- 3% (p less than 0.05), and LA pressures fell from 5.1 +/- 3.6 to 3.7 +/- 2.2 mm Hg (p less than 0.05). Qs fell from 2.4 +/- 0.7 to 1.8 +/- 0.41.min-1.m-2 (p less than 0.05), SOT fell from 425 +/- 154 to 366 +/- 112 ml.O2.min-1.m-2 (p less than 0.05), and oxygen extraction increased from 0.40 +/- 0.12 to 0.46 +/- 0.13 (p less than 0.05). Only one patient did not undergo definitive closure of his defect because of a marked decrease in Qs and SOT with a significant rise in RA pressure. CONCLUSIONS: Although delayed closure of an atrial defect in these patients improved morbidity and mortality, the complete separation of the venous and systemic circulations was accomplished at the expense of decreased Qs and oxygen delivery despite the improved level of arterial oxygenation. The resting levels of oxygen extraction are elevated and will be associated with decreased exercise capability. The long-term benefits of closure of these fenestrations are yet to be shown. PMID- 1617775 TI - Circadian variation in ischemic threshold. A mechanism underlying the circadian variation in ischemic events. AB - BACKGROUND: There is a circadian pattern in the occurrence of cardiac events in patients with coronary artery disease. Whether changes in coronary vascular tone contribute to these phenomena is unknown. We measured the ischemic threshold, defined as either the heart rate or rate-pressure product at 1-mm ST segment depression during treadmill exercise and used it as an index of the lowest coronary vascular resistance; the premise was that when ischemic threshold became lower, coronary vascular resistance was higher, and vice versa. METHODS AND RESULTS: Fifteen patients (group A) with stable coronary artery disease underwent four identical treadmill exercise tests in 24 hours, and ischemic threshold was measured as the heart rate at the onset of 1-mm ST depression. Before each treadmill test, postischemic forearm vascular resistance was measured after 5 minutes of forearm occlusion, using strain-gauge plethysmography. Sixteen additional patients (group B) underwent two treadmill tests at 8 AM and 1 PM, and ischemic threshold was measured as the heart rate-blood pressure product at 1-mm ST depression. A circadian variation was noted: In group A, the heart rate derived ischemic threshold was lower at 8 AM and 9 PM compared with noon and 5 PM (p less than 0.03). Also, in group B, the rate-pressure product-derived ischemic threshold was 8 +/- 2% lower at 8 AM compared with 1 PM (p = 0.008). A circadian variation parallel to the observed variation in ischemic threshold was also noted in the postischemic forearm blood flow, which was lower in the morning and at night (p less than 0.004). There was a strong correlation between postischemic forearm blood flow and ischemic threshold (p less than 0.0001), such that ischemic threshold was lower at the time of day when postischemic forearm blood flow was lower, and vice versa. CONCLUSIONS: A lower ischemic threshold in the morning suggests that the ischemia-induced coronary vascular resistance is increased at this time, a finding supported by a similar variation in postischemic forearm vascular resistance. Parallel changes in forearm and coronary resistance suggest that generalized (neural or humoral factors) rather than local factors are responsible for the observed circadian changes. Increased coronary tone in the mornings may not only contribute to the higher incidence of transient ischemia but may help trigger acute cardiac events at this time. PMID- 1617774 TI - Obstruction of inferior vena caval orifice by giant left atrium in patients with mitral stenosis. A Doppler echocardiographic study from the right parasternal approach. AB - BACKGROUND: To examine whether an extremely enlarged left atrium (giant left atrium) obstructs the venous return from the inferior vena cava (IVC), the velocity of IVC flow was measured at its junction with the right atrium (IVC orifice) in patients with mitral stenosis by use of color and pulsed-wave Doppler echocardiography from a right parasternal longitudinal plane. METHODS AND RESULTS: The maximum dimension of the IVC orifice by two-dimensional echocardiography and the maximum IVC orifice flow velocity by pulsed-wave Doppler echocardiography were measured in 74 patients with mitral stenosis and atrial fibrillation (mean age, 59 years). The control population consisted of 16 subjects with atrial fibrillation alone (mean age, 61 years). Flow velocities in the superior vena cava and hepatic vein were also obtained by pulsed-wave Doppler echocardiography from the supraclavicular and subcostal views, respectively. Fifty-one mitral stenosis patients without severe tricuspid regurgitation were divided into two groups according to the left atrial dimension (LAD), which was measured by the standard left parasternal long-axis view (group A: n = 33, LAD less than 65 mm; group B: n = 18, LAD greater than or equal to 65 mm). Peak inspiratory and expiratory velocities of IVC orifice flow in diastole averaged over three consecutive inspirations in group B (mean +/- SD, 93.4 +/- 32.0 and 47.6 +/- 19.8 cm/sec) were significantly greater (p less than 0.01) than in the control subjects (67.9 +/- 12.8 and 34.5 +/- 7.0 cm/sec) and in group A (70.2 +/- 18.4 and 38.1 +/- 11.5 cm/sec, respectively). However, there were no significant differences in superior vena caval and hepatic vein flow velocities among the three groups. The maximum IVC orifice dimension in group B (11.4 +/- 4.4 mm) was significantly smaller than in the control subjects (20.1 +/- 2.1 mm) and in group A (18.6 +/- 5.4 mm) because of displacement of the atrial septum into the right atrium. There were significant negative correlations between the IVC orifice dimension and the peak IVC orifice flow velocity (r = -0.62, SEE = 0.33 cm/sec, n = 67, y = e(-0.01x + 3.6), p less than 0.01) as well as the left atrial dimension (r = -0.71, SEE = 0.32 mm, n = 67, y = e(-0.02x + 3.8), p less than 0.01) in these 51 patients and control subjects. In the remaining 23 patients with severe tricuspid regurgitation, the peak inspiratory IVC orifice velocity (n = 9, 88.6 +/- 30.0 cm/sec) was significantly greater (p less than 0.05) and the IVC orifice dimension (23.8 +/- 9.7 mm) significantly smaller (p less than 0.05) in patients with a giant left atrium than in those without (n = 14, 69.9 +/- 15.3 cm/sec and 30.5 +/- 9.6 mm, respectively); in the latter, the IVC orifice dimension was significantly (p less than 0.05) greater than in the controls. CONCLUSIONS: A giant left atrium in patients with mitral stenosis obstructs venous return at the IVC orifice by marked displacement of the atrial septum toward the right atrium. PMID- 1617776 TI - Adrenergic effects on reentrant ventricular rhythms in subacute myocardial infarction. AB - BACKGROUND: Reentry has been shown to be a mechanism of ventricular arrhythmias elicited by programmed premature stimulation in the subacute ischemic period of dogs subjected to myocardial infarction. The spatial distribution of refractoriness in these hearts has been shown to play an important part in the formation of functional arcs of conduction block during programmed ventricular stimulation. Because the adrenergic nervous system influences cardiac arrhythmias and myocardial infarction can directly affect sympathetic innervation in the heart, we investigated the role of the sympathetic nervous system on reentry in the canine heart 4 days after infarction. METHODS AND RESULTS: The influences of adrenergic stimuli on the initiation of reentrant ventricular excitation were studied using a 128-channel computerized recording system in the canine heart 4 days after ligation of the left anterior descending coronary artery. Bilateral stimulation of the ansae subclavia preferentially improved conduction of premature beats in the normal zones. This corresponded to an improvement in excitability, as measured by a decrease in stimulus strength at the same premature coupling interval as control. Consequently, the effective refractory period was preferentially shortened at normal sites but not at ischemic sites. Both of these changes contributed to a shift of the arc of functional conduction block toward more normal tissue. As a result, sites proximal to the arc of functional conduction block had more time to recover excitability and thereby were available to be reexcited by the distal activation wave front. Conversely, intravenous infusion of norepinephrine preferentially shortened the effective refractory period of sites in the ischemic zone, thereby indicating that denervation hypersensitivity had occurred at these sites. The spatial dispersion of refractoriness and the arc of functional conduction block were significantly reduced in size. As a consequence, previously inducible reentrant rhythms were no longer inducible. CONCLUSIONS: Sympathetic stimulation can be considered an arrhythmogenic intervention, whereas norepinephrine infusion may be considered antiarrhythmic in this experimental model. PMID- 1617777 TI - Effects of inhibition of nitric oxide formation on regional blood flow in experimental myocardial infarction. AB - BACKGROUND: Large myocardial infarction is associated with reactive hypertrophy and dilation of the left ventricle, depressed coronary flow reserve, and the development of heart failure including systemic vasoconstriction. We hypothetized that changes in endothelial function, e.g., in the synthesis or action of nitric oxide in the coronary and peripheral vasculatures, might be involved in the depressed coronary flow reserve and increased systemic vascular resistance observed in postinfarction myocardial hypertrophy and failure. METHODS AND RESULTS: The regional blood flow changes that occur as a result of inhibiting the basal release of nitric oxide with NG-monomethyl-L-arginine (L-NMMA) and how this regional pattern may be altered in large MI (infarct size, 30-51% of left ventricle) were examined. Measurements were made 24 hours and 8 weeks after myocardial infarction or sham operation in conscious rats. The left ventricular end-diastolic pressure and effects of L-NMMA on left ventricular end-diastolic pressure was similar 24 hours and 8 weeks after myocardial infarction. The effects of L-NMMA (30 mg/kg i.v.) on heart rate and blood pressure were similar in infarcted and sham animals. L-NMMA exerted a marked vasoconstriction in the renal, splanchnic, cutaneous, and cerebral circulations of similar magnitude in sham-operated rats and animals with myocardial infarction. The coronary vasoconstrictor effect of L-NMMA was attenuated significantly in the hypertrophied right and noninfarcted left ventricle of 8-week-old infarcted rats (p less than 0.01 versus sham-operated animals) but not 24 hours after induction of myocardial infarction when cardiac hypertrophy has not yet developed. The increase in left ventricular coronary resistance in 8-week-old infarcted animals was inversely related to infarct size (r = -0.787, p = 0.012, n = 9). Nitroglycerin exerted similar increases in coronary blood flow in rats with chronic myocardial infarction and sham-operated animals, arguing against a reduced vascular responsiveness to nitric oxide. Transmission electron microscopy of coronary resistance vessels in 8-week-old infarcted animals did not reveal endothelial abnormalities. CONCLUSIONS: These data suggest that the basal release of nitric oxide in the renal, intestinal, and cutaneous circulations is not affected adversely in this model of myocardial infarction and failure. However, the blunted coronary vasoconstrictor effect of L-NMMA late after large myocardial infarction supports the view that the basal release of nitric oxide is impaired in postinfarction reactive cardiac hypertrophy. PMID- 1617778 TI - Noninvasive measurement of the time constant of left ventricular relaxation using the continuous-wave Doppler velocity profile of mitral regurgitation. AB - BACKGROUND: The time constant of isovolumic relaxation (tau) is an important parameter of ventricular diastolic function, but the need for invasive measurement with high-fidelity catheters has limited its use in general clinical cardiology. The Doppler mitral regurgitant velocity spectrum can be used to estimate left ventricular (LV) pressure throughout systole and may provide a new noninvasive method for estimating tau. METHODS AND RESULTS: Mitral regurgitation was produced in nine dogs, and ventricular relaxation was adjusted pharmacologically and with hypothermia. High-fidelity ventricular pressures were recorded, and tau was calculated from these hemodynamic data (tau H) assuming a zero-pressure asymptote. Continuous-wave mitral regurgitant velocity profiles were obtained, and the ventriculo-atrial (VA) pressure gradient was calculated by the simplified Bernoulli equation; tau was calculated from the Doppler data from the time of maximal negative dP/dt until LV-LA pressure crossover. Three methods were used to correct the Doppler VA gradient to better approximate the LV pressure before calculating tau: 1) adding actual LA V wave pressure (to yield tau LA); 2) adding 10 mm Hg (tau 10); and 3) no adjustment at all (actual VA gradient used to calculate tau 0). The agreement between tau H and the three Doppler estimates of tau was assessed by linear regression and by the mean and standard deviation of the error between the measurements (delta tau). the measurements (delta tau). tau H ranged from 29 to 135 msec. Without correction for LA pressure, the Doppler estimate of tau seriously underestimated tau H: tau 0 = 0.30 tau H + 9.4, r = 0.79, delta tau = -35 +/- 18 msec. This error was almost completely eliminated by adding actual LA pressure to the VA pressure gradient: tau LA = 0.92 tau H + 7.6, r = 0.95, delta tau = 2 +/- 7 msec. Addition of a fixed LA pressure estimate of 10 mm Hg to the VA gradient yielded an estimate that was almost as good: tau 10 = 0.89 tau H + 4.9, r = 0.88, delta tau = -2 +/- 12 msec. In general, tau was overestimated when actual LA pressure was below this assumed value, and vice versa. Numerical analysis demonstrated that assuming LA pressure to be 10 mm Hg should yield estimates of tau accurate to +/- 15% between true LA pressures of 5 and 20 mm Hg. CONCLUSIONS: This study demonstrates that the Doppler mitral regurgitant velocity profile can be used to provide a direct and noninvasive measurement of tau. Because mitral regurgitation is very common in cardiac patients, this method may allow more routine assessment of tau in clinical and research settings, leading to a better understanding of the role of impaired ventricular relaxation in diastolic dysfunction and the effect of therapeutic interventions. PMID- 1617779 TI - Protamine releases endothelium-derived relaxing factor from systemic arteries. A possible mechanism of hypotension during heparin neutralization. AB - BACKGROUND: When used to reverse the anticoagulant effect of heparin, protamine sulfate often causes vasodilation that can lead to systemic hypotension. Protamine is rich in the basic amino acid arginine, which is the precursor of endothelial cell synthesis of nitric oxide, and nitric oxide is the active component of endothelium-derived relaxing factor (EDRF). METHODS AND RESULTS: To determine whether the hypotensive effect of protamine could be due to stimulated release of EDRF, we studied rings (4-5 mm) of canine coronary, femoral, and renal artery suspended in organ chambers containing physiological salt solution (37 degrees C and 95% O2-5% CO2). Arterial rings with and without endothelium were contracted with prostaglandin F2 alpha (2 x 10(-6) M) and exposed to increasing concentrations of protamine (final organ bath concentration, 40-400 micrograms/ml). In arterial segments without endothelium, protamine caused only a modest decrease in tension. However, protamine induced concentration-dependent relaxation in all arterial segments with endothelium, which was significantly greater than in segments without endothelium (p less than 0.05). The endothelium dependent relaxation induced by protamine was inhibited by NG-monomethyl-L arginine (L-NMMA) (10(-5) M), but L-NMMA had no effect on rings without endothelium. The action of L-NMMA could be reversed by L-arginine (10(-4) M) but not D-arginine (10(-4) M). CONCLUSIONS: This study demonstrates that protamine stimulates the release of EDRF from arterial endothelium, and that endothelium dependent vasodilation may be an important cause of systemic hypotension during protamine infusion. PMID- 1617780 TI - Efficacy of antiarrhythmic drugs in patients with arrhythmogenic right ventricular disease. Results in patients with inducible and noninducible ventricular tachycardia. AB - BACKGROUND: Ventricular tachyarrhythmias are the major clinical manifestation of arrhythmogenic right ventricular disease. Although antiarrhythmic therapy has been widely advocated, there is only limited information available on the efficacy of antiarrhythmic drugs in these patients. METHODS AND RESULTS: The short- and long-term efficacies of various antiarrhythmic agents were retrospectively and prospectively analyzed in 81 patients (mean age, 39 +/- 14 years; range, 16-68 years; 61.7% males) with arrhythmogenic right ventricular disease. In 42 patients with inducible ventricular tachycardia during programmed ventricular stimulation, the following efficacy rates were obtained: class Ia and Ib drugs (n = 18), 5.6%; class Ic drugs (n = 25), 12%; beta-blockers (n = 8), 0%; sotalol (n = 38), 68.4%; amiodarone (n = 13), 15.4%; verapamil (n = 5), 0%; and drug combinations (n = 26), 15.4%. Only one of the 10 patients not responding to sotalol was treated effectively by amiodarone, whereas the remaining nine patients proved to be drug refractory toward all other drugs tested (3.8 +/- 2.3 drugs, including amiodarone in five cases) and underwent nonpharmacological therapy. During a follow-up of 34 +/- 25 months, three of the 31 patients (9.7%) discharged on pharmacological therapy had nonfatal recurrences of ventricular tachycardia after 0.5, 51, and 63 months, respectively. In 39 patients with noninducible ventricular tachycardia during programmed ventricular stimulation, the following efficacy rates were observed: class Ia and Ib drugs (n = 16), 0%; class Ic agents (n = 23), 17.4%; beta-blockers (n = 7), 28.6%; sotalol (n = 35), 82.8%; amiodarone (n = 4), 25%; verapamil (n = 24), 50%; and drug combinations (n = 11), 9.1%. During a follow-up of 14 +/- 13 months, four of 33 patients (12.1%) discharged on antiarrhythmic drugs had nonfatal relapses of their clinical ventricular arrhythmia. CONCLUSIONS: Thus, in arrhythmogenic right ventricular disease, sotalol proved to be highly effective in patients with inducible as well as noninducible ventricular tachycardia. Patients with inducible ventricular tachycardia not responding to sotalol are likely to not respond to other antiarrhythmic drugs and should be considered for nonpharmacological therapy without further drug testing. Amiodarone did not prove to be more effective than sotalol and may not be an alternative because of frequent side effects during long-term therapy, especially in young patients. Verapamil and beta-blockers were effective in a considerable number of patients with noninducible ventricular tachycardia and may be a therapeutic alternative in this subgroup. Class I agents appear to be rarely effective in the treatment of both inducible and noninducible ventricular tachycardia in arrhythmogenic right ventricular disease. PMID- 1617781 TI - Metabolic consequences and predictability of ventricular fibrillation in hypoxia. A 31P- and 23Na-nuclear magnetic resonance study of the isolated rat heart. AB - BACKGROUND: Ventricular fibrillation has deleterious metabolic and functional consequences for the heart. This study had two purposes: first, to define the effects of ventricular fibrillation during hypoxia on energy metabolism and accumulation of intracellular Na+ and, second, to test whether the occurrence of ventricular fibrillation can be predicted from functional or metabolic parameters. METHODS AND RESULTS: Isolated isovolumic rat hearts were perfused with oxygenated Krebs-Henseleit buffer at 37 degrees C. After a prehypoxic period, hearts were subjected to hypoxic perfusion (95% N2-5% CO2) for 30 minutes. High-energy phosphates and intracellular pH were determined by 31P nuclear magnetic resonance (NMR) spectroscopy, and intracellular Na+ accumulation was followed by 23Na-NMR spectroscopy in combination with the shift reagent dysprosium triethylenetetraminehexa-acetate. Five of 10 (31P-NMR) and four of 10 (23Na-NMR) hearts developed spontaneous ventricular fibrillation at 19 +/- 2 minutes (31P-NMR) and 18 +/- 3 minutes (23Na-NMR) of hypoxia (ventricular fibrillation group), whereas other hearts (non-ventricular fibrillation group) remained beating throughout hypoxia. Cardiac function and high-energy phosphate content declined during hypoxia, and ventricular fibrillation exacerbated this decline significantly. Similarly, ventricular fibrillation exacerbated the accumulation of intracellular Na+ occurring during hypoxia. Statistical analysis showed that the event of ventricular fibrillation could be predicted from changes of end-diastolic pressure, rate-pressure product, and creatine phosphate content before ventricular fibrillation. However, the strongest predictor of ventricular fibrillation was intracellular Na+ accumulation, which occurred in ventricular fibrillation hearts throughout the hypoxic period long before ventricular fibrillation was initiated. CONCLUSIONS: Loss of systolic and diastolic functions, creatine phosphate depletion, and, in particular, intracellular Na+ accumulation may be causally related to induction of ventricular fibrillation during hypoxia, all of which are most likely linked to concomitant intracellular Ca2+ accumulation. PMID- 1617782 TI - Age as a modulator of coronary capillary angiogenesis. PMID- 1617783 TI - Intravascular ultrasound. Research technique or clinical tool? PMID- 1617784 TI - A normal coronary artery: what size is it? PMID- 1617785 TI - Sinus node during atrial fibrillation. To beat or not to beat? PMID- 1617787 TI - Standardization of cardiac tomographic imaging. From the Committee on Advanced Cardiac Imaging and Technology, Council on Clinical Cardiology, American Heart Association; Cardiovascular Imaging Committee, American College of Cardiology; and Board of Directors, Cardiovascular Council, Society of Nuclear Medicine. PMID- 1617786 TI - Are restenosis cells containing nonmuscle myosin really vascular smooth muscle cells? PMID- 1617788 TI - Statement on exercise. Benefits and recommendations for physical activity programs for all Americans. A statement for health professionals by the Committee on Exercise and Cardiac Rehabilitation of the Council on Clinical Cardiology, American Heart association. PMID- 1617789 TI - Myocardial viability in patients with Q wave myocardial infarction and no residual ischemia. AB - BACKGROUND: Coronary revascularization in patients with persistent angina after myocardial infarction reduces the incidence of recurrent angina pectoris and myocardial infarction and improves left ventricular function. The results of revascularization after a Q wave myocardial infarction when there is no residual ischemia may depend on myocardial viability. METHODS AND RESULTS: To determine whether there was viable myocardium in the infarct area in the absence of clinical and scintigraphic evidence of myocardial ischemia, 15 asymptomatic patients with a Q wave myocardial infarction, no redistribution on stress 201Tl test, and single-vessel disease (greater than 70% stenosis) with persistent anterograde blood flow were randomized to percutaneous transluminal coronary artery angioplasty (PTCA) or conservative medical treatment. After 2 months of follow-up, mean coronary blood flow measured by Doppler catheter in the infarct related artery was higher in the PTCA treatment group (33 +/- 6 ml/min, n = 8) than in the conservative treatment group (16 +/- 4 ml/min, n = 7; p less than 0.05 between groups). The 201Tl pathological-to-normal ratios measured on postexercise images did not change in patients treated conservatively during the follow-up period (delta = +1.1 +/- 2.2%; NS from baseline) but increased significantly in patients treated by PTCA (delta = +8.5 +/- 2.3%; p less than 0.01 from baseline; p less than 0.05 between groups). Segmental wall motion improved on left ventricular angiography 2 months after PTCA (delta = +11.5 +/- 2.2%; p less than 0.001 from baseline) significantly more than in the conservative treatment group (delta = +4.1 +/- 1.4%; p less than 0.05 between both groups). Improvements of 201Tl ratios and segmental wall motion indexes correlated significantly (r = 0.73, p = 0.002). The mild improvement of global left ventricular ejection fraction measured in the PTCA treatment group did not differ significantly from changes in the conservative treatment group. CONCLUSIONS: Successful angioplasty of the stenotic infarct artery in patients with a Q wave myocardial infarction and no residual ischemia improved coronary flow, 201Tl uptake in the infarct area, and regional wall motion. Therefore, myocardial viability may last several weeks, as long as residual blood flow persists in the infarct-related artery. Optimal assessment of viability by imaging techniques should identify patients who are most likely to benefit from revascularization. PMID- 1617791 TI - Contribution of localized calcium deposits to dissection after angioplasty. An observational study using intravascular ultrasound. AB - BACKGROUND: Atherosclerotic plaque fracture and dissection of the arterial wall are frequent concomitants of the balloon angioplasty process. The composition and morphology of plaque within the vessel may be critical in determining the extent of plaque fracture and dissection during balloon angioplasty. To examine this potential association in the clinical setting, we studied patients with intravascular ultrasound imaging after balloon angioplasty. METHODS AND RESULTS: Forty-one patients were studied with intravascular ultrasound after angioplasty in both peripheral and coronary arteries. Ultrasound images representing the target lesion cross section were digitized, stored on computer, and analyzed off line. The presence of intralesional calcium and the relative size of dissection for each lesion was computed. Thirty-one patients (76%) had ultrasound evidence of significant dissection or plaque fracture immediately after balloon dilation. In 23 of 31 (74%) of the lesions, the ultrasound scans showed significant localized calcium deposits within the plaque substance. In 87% of these cases, the dissections were adjacent to the calcific portion of the vessel wall. In addition, the relative size of dissections referenced to the neolumen area were significantly larger (p less than or equal to 0.002) in the calcified vessels (27.5 +/- 12.3%) compared with the size of the dissections in lesions without calcium (11.2 +/- 5.8%). CONCLUSIONS: The presence of calcium within the vessel wall appeared to be significantly associated with both the location and size of the dissected tissue arm from the vessel wall. These data suggest that localized calcium deposits have a direct role in promoting dissection, presumably by increasing shear stresses within the plaque. PMID- 1617792 TI - Excimer laser-facilitated coronary angioplasty. Relative risk analysis of acute and follow-up results in 200 patients. AB - BACKGROUND: Excimer laser coronary angioplasty has been reported to be a promising treatment for complex coronary artery disease. The purpose of this study was to define the predictors of acute success and restenosis after this experimental intervention. METHODS AND RESULTS: A cohort of 200 consecutive patients had a minimum of 6 months of follow-up evaluation after treatment of 215 coronary stenoses that were carefully selected for excimer laser coronary angioplasty. At the time of the initial procedure, the laser catheter alone produced a residual stenosis of less than or equal to 50% at 119 of 215 lesions (55.4%). For complete dilatation, 87.9% of the lesions required adjunctive balloon angioplasty. Clinical success was achieved in 183 of the 200 patients (91.5%), as indicated by a reduction by at least 20% of the narrowing of the vessel diameter, less than or equal to 50% residual stenosis, and no in-hospital complication. Complications included abrupt closure (5.0%), myocardial infarction (3.5%), bypass surgery (3.0%), perforation (2.0%), and death (0.0%). Logistic regression analysis showed that lesions at vessel bifurcations (success rate, 66%; adjusted odds ratio [OR] = 0.16; p = 0.002) or in tortuous vessels (success rate, 82%; OR = 0.48; p = 0.004) were associated with decreased clinical success. However, acceptable success rates were achieved in patients with lesions in saphenous vein grafts more than 3 years old (success rate, 94%; OR = 1.40; p = 0.75), in ostial lesions (success rate, 100%; OR = 3.36; p = 0.43), and in lesions longer than 10 mm (success rate, 93.5%; OR = 1.50; p = 0.39). Clinical follow-up was available in 197 of the 200 patients (98.5%) a mean of 5.9 +/- 1.9 months after angioplasty, at which time 31.0% of patients had developed symptoms or evidence of ischemia. No patient died during the study. Follow-up angiography was obtained in 83.1% of eligible patients after a mean [+/- SD] of 5.2 +/- 2.0 months. Angiographic restenosis, defined by greater than 50% stenosis, appeared at 78 of 164 lesions (47.6%). By logistic regression analysis, only lesions in saphenous vein grafts were associated with a decreased rate of restenosis (restenosis rate, 20%; OR = 0.18; p = 0.01). CONCLUSIONS: This analysis, which defines the profile of risk for excimer laser angioplasty, provides a sound basis for rigorous comparison of adjunctive excimer laser with balloon angioplasty for ostial narrowings, long lesions, and saphenous vein graft stenoses. PMID- 1617793 TI - Determinants of infarct size in reperfusion therapy for acute myocardial infarction. AB - BACKGROUND: Experimental animal studies have demonstrated that myocardium at risk, residual collateral flow, and duration of coronary artery occlusion are important determinants of final infarct size. The present study examined these variables in patients with acute myocardial infarction in relation to final infarct size. METHODS AND RESULTS: Myocardium at risk was assessed with hexakis(2 methoxyisobutyl isonitrile) technetium (I) (99mTc sestamibi) in 89 patients with first-time myocardial infarction (anterior, 48 patients; inferior, 41 patients). All patients had successful reperfusion therapy with either intravenous thrombolysis (32 patients) or primary coronary angioplasty (57 patients) within 24 hours of the onset of chest pain (4.7 +/- 3.9 hours; range, 0.5-21.5 hours) documented by coronary angiography. 99mTc sestamibi was injected intravenously before reperfusion therapy, and tomographic imaging was performed 1-6 hours later. Myocardium at risk was quantitated for each patient and expressed as a percentage of the left ventricle: 35 +/- 19%; range, 2-73%. Collateral flow was estimated by both invasive and noninvasive methods. Fifty-three patients with TIMI grade 0 or I flow who underwent primary coronary angioplasty had collateral flow graded angiographically (0-3) before the first balloon inflation. All patients had collateral flow estimated noninvasively from the acute sestamibi short-axis profile curve by three methods that assess the severity of the perfusion defect. Each of these three methods was significantly associated with angiographic collateral grade. Final infarct size was determined at hospital discharge by a second sestamibi study (17 +/- 17%; range, 0-59%). Myocardium at risk (r = 0.61, p less than 0.0001), angiographic collateral grade (p = 0.0003), and radionuclide estimates of collateral flow (r = 0.69-0.70, all p less than 0.0001) were all significantly associated with final infarct size. The time to reperfusion therapy was not significantly associated with final infarct size by univariate analysis (r = 0.18, p = 0.10). Two multivariate models were constructed to determine which variables were independently associated with final infarct size. In the invasive model, myocardium at risk, angiographic collateral grade with an interaction term for infarct location, and time to reperfusion were all independently significant and accounted for 70% of the variability in final infarct size. The noninvasive model, which substituted a radionuclide estimate of collateral flow for angiographic collateral grade, showed nearly identical results, accounting for 68% of the variability in infarct size in patients where the infarct artery was known to be occluded. When all patients were included (patients with and without acute angiography), the noninvasive model accounted for 59% of the variability in infarct size. CONCLUSIONS: Myocardium at risk, collateral flow, and duration of coronary occlusion are each independently associated with final infarct size and account for most of its variability. Ideally, all three parameters should be examined in evaluation of the efficacy of new treatment strategies for acute myocardial infarction. PMID- 1617790 TI - Angioplasty triggers intracoronary leukotrienes and lipoxin A4. Impact of aspirin therapy. AB - BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) is a widely used and important method of reperfusing coronary arteries. However, it is also associated with serious complications such as acute reocclusion and accelerated restenosis. The factors as well as the mechanisms involved in PTCA-associated complications remain to be fully elucidated. Because peptidoleukotrienes and lipoxins are potent vasoactive compounds, the formation of which is not inhibited by aspirin (ASA) treatment in vitro, it is possible that these eicosanoids are involved in PTCA-associated untoward events. To test this, we determined the intracoronary levels of peptidoleukotrienes and lipoxin A4 (LXA4) as well as thromboxane (TX) and 5S,12S-dihydroxyeicosatetraenoic acid (5S,12S-DiHETE; a product of double dioxygenation) after plaque rupture and evaluated the impact of ASA therapy. METHODS AND RESULTS: PTCA was performed on 12 patients with coronary artery disease, six undergoing ASA therapy and six without ASA therapy, for at least 2 weeks before PTCA. By means of a technique that permitted sampling of intracoronary blood at the plaque site in situ, samples were taken immediately before and 10 seconds after initiation of plaque rupture. Lipoxygenase (LO) derived products, including LXA4 and 5S,12S-DiHETE, and a marker of cyclooxygenase activity, i.e., TXB2, were quantitated after extraction and chromatography using deuterium-labeled internal standards and electron capture negative ion chemical ionization mass spectrometry. Peptidoleukotrienes (LTC4 and LTD4) were quantitated after reverse-phase high-performance liquid chromatography coupled with radioimmunoassay. Intracoronary blood taken before PTCA showed no detectable levels of these eicosanoids (the minimum limits of detection were within the picomole range). In contrast, each of these LO products was detected after PTCA. Patients undergoing ASA treatment showed elevated levels of each LO product examined compared with those not receiving ASA. Eicosanoid levels were (mean +/- SEM): LTC4, 7.10 +/- 1.22 ng/ml (ASA) versus 0.48 +/- 0.10 ng/ml; LTD4, 4.92 +/- 0.56 ng/ml (ASA) versus 1.17 +/- 0.48 ng/ml; LXA4, 24.98 +/- 4.11 ng/ml (ASA) versus 15.83 +/- 2.43 ng/ml; 5S,12S-DiHETE, 19.47 +/- 3.98 ng/ml (ASA) versus 11.98 +/- 1.83 ng/ml; TXB2, complete blockage (ASA) versus 31.04 +/- 7.38 ng/ml (p less than 0.05 for LTC4 and LTD4). To distinguish between dilatation of whole blood versus dilatation of whole blood and atheroma for contribution of eicosanoids, we also monitored their formation in Gore-tex grafts. Upon balloon inflation, TXB2 was generated, but LO products were not detected. In contrast, injection of platelet- and leukocyte-directed agonists within the graft led to both peptidoleukotriene and lipoxin formation. CONCLUSIONS: The results indicate that PTCA triggers the intraluminal release of peptidoleukotrienes and LXA4 and that ASA therapy enhances their appearance in intracoronary blood. In addition, they provide direct evidence for LO products (LTC4, LTD4, and LXA4) in a local milieu in vivo. Moreover, the presence of the double dioxygenation product 5S,12S DiHETE (a potential marker of 5- and 12-LO interactions) suggests that transcellular metabolic events can contribute to eicosanoid formation in vivo. PMID- 1617794 TI - Balloon mitral commissurotomy after previous surgical commissurotomy. The National Heart, Lung, and Blood Institute Balloon Valvuloplasty Registry participants. AB - BACKGROUND: Mitral restenosis after surgical mitral commissurotomy often occurs within 5-15 years, necessitating a repeat procedure. Balloon mitral commissurotomy (BMC) has been advocated as an alternative to repeat surgery for mitral restenosis. METHODS AND RESULTS: The purposes of this study are to determine the short- and intermediate-term outcomes of patients undergoing BMC after previous surgical commissurotomy, to compare these patients with those undergoing balloon mitral commissurotomy as an initial procedure, and to elucidate the multivariate determinants of acute procedural and clinical outcome. Of 738 patients undergoing BMC as part of the National Heart, Lung, and Blood Institute Balloon Valvuloplasty Registry, 133 underwent BMC after previous surgical mitral commissurotomy. Prospective data obtained included demographic, hemodynamic, echocardiographic, and clinical follow-up. BMC after previous surgical commissurotomy produced a significant reduction in transvalvular gradient from 13 +/- 5 to 6 +/- 3 mm Hg (p less than 0.0001) and an increase in mitral valve area from 1.0 +/- 0.3 to 1.8 +/- 0.8 cm2 (p less than 0.0001). BMC as an initial procedure increased valve area from 1.0 +/- 0.4 to 2.0 +/- 0.8 cm2 (p less than 0.0001) (p = 0.03 versus prior surgery). Baseline characteristics including mitral valve echo score were similar for both groups. Comparing 6-month status in patients with prior surgery to those without, 80% versus 90% were New York Heart Association (NYHA) functional class I or II (p = 0.004). Mortality was similar. In patients with previous mitral valve surgery, multivariate predictors of improvement in 6-month clinical status included the experience of the center (p = 0.006), lower echocardiographic score (p = 0.001), and lower left ventricular end-diastolic pressure (p = 0.008). Multivariate determinants of a final mitral valve area greater than or equal to 1.5 cm2 were a lower baseline NYHA functional class (p = 0.003) and lower mitral valve echocardiographic score (p = 0.008). CONCLUSIONS: BMC after previous surgical mitral commissurotomy results in similar hemodynamic changes as in patients undergoing BMC as an initial procedure. Symptomatic improvement at 6 months is slightly less frequent in prior commissurotomy patients. Patients with favorable valvular morphology and preserved left ventricular function who undergo BMC in experienced centers are most likely to achieve symptomatic improvement after previous surgical commissurotomy. In general, BMC is an effective treatment for mitral restenosis after previous surgical commissurotomy. PMID- 1617795 TI - Signal transduction in endocrine tissues. PMID- 1617796 TI - Computerized tomography versus magnetic resonance imaging: a comparative study in hypothalamic-pituitary and parasellar pathology. AB - OBJECTIVE: We wished to analyse the relative value of computerized tomography and magnetic resonance in patients referred for evaluation of pituitary and parasellar lesions. DESIGN: We performed a separate evaluation by two independent neuroradiologists of computerized tomography and magnetic resonance images ordered numerically and anonymously, with no clinical data available. PATIENTS: We studied 40 patients submitted for hypothalamic-pituitary study; 31 were carried out preoperatively, of which histological confirmation later became available in 14. The remaining nine patients were evaluated postoperatively. MEASUREMENTS: Over 40 parameters relating to the bony margins, cavernous sinuses, carotid arteries, optic chiasm, suprasellar cisterns, pituitary, pituitary stalk and extension of the lesion were evaluated. These reports were compared with the initial ones offered when the scans were ordered, and with the final diagnosis. RESULTS: Concordance between initial computerized tomography and magnetic resonance was observed in 27 cases (67.5%); among the discordant cases computerized tomography showed the lesion in two, magnetic resonance in 10, while in the remaining case reported to harbour a microadenoma on computerized tomography the differential diagnosis between a true TSH-secreting microadenoma and pituitary resistance to thyroid hormones is still unclear. Both neuroradiologists coincided in their reports in 32 patients (80%); when the initial report was compared with those of the neuroradiologists, concordance was observed with at least one of them in 34 instances (85%). Discordant results were observed principally in microadenomas secreting ACTH or PRL and in delayed puberty. In the eight patients with Cushing's disease (histologically confirmed in six) magnetic resonance was positive in five and computerized tomography in two; the abnormal image correctly identified the side of the lesion at surgery. CONCLUSIONS: In patients referred for evaluation of Cushing's syndrome or hyperprolactinaemia (due to microadenomas) or after surgery, magnetic resonance is clearly preferable to computerized tomography. In macroadenomas both scans are equally diagnostic but magnetic resonance offers more information on pituitary morphology and neighbouring structures. Nevertheless, there are cases in which the results of computerized tomography and magnetic resonance will complement each other, since different parameters are analysed with each examination and discordant results are encountered. PMID- 1617797 TI - Reactivity to stress and psychological adjustment in adults with pituitary insufficiency. AB - OBJECTIVE: Hypopituitary adults who were affected during childhood have a below average rate of marriage, a rate of unemployment that exceeds national norms, and often indicate dissatisfaction with their life circumstances. We undertook the present study to determine the effects of short stature versus those of pituitary hormone deficiency. DESIGN AND PATIENTS: We compared hypopituitary adults (n = 25) with normal short adults (n = 25) who were matched for height, sex, age and socioeconomic status. MEASUREMENTS: In these two groups of subjects, we compared the physiological responses to a simulated social stressor, a public speaking task, and we measured the psychometric attributes that are indicators of social assertiveness and extraversion. RESULTS: Before, during and after the stress of public speaking, patients with multiple pituitary hormone deficiencies (n = 20) had lower mean systolic and diastolic blood pressures than controls, while patients with isolated growth hormone deficiency (n = 5) were equivalent to controls. The reactivity to stress, assessed using delta scores based on changes in blood pressure and heart rate, was also decreased in multiple hormone deficient patients. Psychometric test results indicated that patients with multiple hormone deficiencies showed lower openness, lower assertiveness, greater neuroticism and a tendency towards less extraversion than did controls. The responses of patients with isolated GH deficiency on the psychometric tests were not statistically different from controls, but the number of subjects in this group (n = 5) was too small to draw conclusions. CONCLUSIONS: The impaired cardiovascular responses to stress in patients with multiple hormone deficiencies, compared to short control subjects and to patients with GH deficiency leads us to conclude that factors other than stature and GH are responsible for these observations. The differences might be related to insufficiency of catecholamines or cortisol in the patients with multiple hormone deficiencies. These hormonal deficiencies might also account for the socially inhibited behaviour of these patients. Our results suggest that more attention needs to be directed at preparing hypopituitary patients for the challenges of adulthood. Also, these patients may be helped by more intensive efforts at hormonal replacement in adulthood. PMID- 1617798 TI - Abnormalities of the hypothalamo-pituitary-gonadal axis after head injury. AB - OBJECTIVE: We aimed to investigate the mechanisms of hypogonadism which develops after head injury. DESIGN: Pulsatile secretion of LH was studied in subjects 6-10 days after major head injury. PATIENTS: We studied five male subjects admitted with major head injuries and six healthy age-matched control subjects. MEASUREMENTS: During the pulsatility study, LH was measured at 5-minute intervals for 4 hours and 15-minute intervals for a further 2 hours. In addition, testosterone and LH were measured on Days 1-5, 14 and after 3-6 months. RESULTS: The analysis of pulsatile secretion of LH demonstrated an LH pulse frequency similar to control subjects, but a significantly reduced LH pulse amplitude (P less than 0.001, fixed threshold method; P less than 0.02, Detect method). Both testosterone and LH levels were reduced after injury with the nadir occurring on Day 4. CONCLUSIONS: Hypogonadism after head injury is due to defective LH secretion, with normal pulse frequency but a reduced pulse amplitude. PMID- 1617799 TI - Differential effects of arginine on growth hormone releasing hormone and insulin induced growth hormone secretion. AB - OBJECTIVE: We wished to investigate the interaction of arginine, GHRH and insulin stress on GH secretion. DESIGN: Six healthy, non-obese volunteers underwent seven separate studes in random order. They received (1) insulin alone at 0 minutes; (2) GHRH alone at 15 minutes; (3) arginine alone at 0-30 minutes; (4) arginine at 0-30 minutes and GHRH at 15 minutes; (5) insulin at 0 minutes and arginine at 0 30 minutes; (6) insulin at 0 minutes, GHRH at 15 minutes and arginine at 0-30 minutes; (7) insulin at 0 minutes and GHRH at 15 minutes. MEASUREMENTS: GH and PRL were measured from -30 to 150 minutes at intervals of 15 minutes. RESULTS: Arginine increased GH responses to GHRH and decreased GH responses to hypoglycaemia, but this inhibitory effect of arginine was reversed by GHRH. CONCLUSIONS: The findings suggest that arginine-induced GH release is mainly mediated by a decrease in somatostatinergic tone, while GH responses to insulin stress are probably mediated by both an increase in hypothalamic GHRH release and inhibition of somatostatin. PMID- 1617800 TI - Percutaneous ethanol injection treatment of autonomous thyroid adenoma: hormonal and clinical evaluation. AB - OBJECTIVE: We have evaluated the efficacy of percutaneous ethanol injection as an alternative to surgery and iodine-131 treatment in solitary autonomous thyroid adenoma. DESIGN: Percutaneous ethanol injection (0.5-2.8 ml ethanol/ml nodular tissue) was performed under sonographic guidance in 3-5 (1-2 weekly) sessions; a 7.5 MHz linear real-time scanner (Toshiba, mod. 32B) was used for sonographic studies. The thyroid hormone profile was assessed during treatment and for the next 6 months. PATIENTS: Fifty-six patients (40 females, 16 males, mean age 46 +/ SD 9 years; 30 pretoxic, 26 toxic) were included in the study: their pretreatment technetium-99 m thyroid scan showed a single hot nodule with total suppression of extranodular tissue in 45 and near-total suppression in 11. MEASUREMENTS: Thyroid hormones, antithyroglobulin and antiperoxidase antibodies were measured by specific radioimmunoassay, while thyrotrophin was evaluated by ultrasensitive immunoradiometric assay. RESULTS: Apart from a case of transient pyrexia, no relevant adverse effects were observed. A slight thyroid hormone increase was seen in both groups immediately following a treatment. Six months after therapy a biochemical and clinical remission of hyperthyroidism was observed in 18 out of 22 toxic patients (81.8%); a significant increase of TSH levels was seen in both groups (P less than 0.01). With follow-up, significant volume shrinkage (P less than 0.001) as well as structural alterations of the nodule were consistently recorded at sonography; a linear relationship (r = 0.98; P less than 0.0001) between pretreatment volume and volume reduction was found. At scintiscan, functional activity of extranodular parenchyma was found in 40 out of 56 patients (71.4%), 16/26 (61.5%) in the hyperthyroid group, 24/30 (80.0%) in the pretoxic group. CONCLUSIONS: These data confirm that percutaneous ethanol injection is effective in obtaining functional ablation and in inducing remission of hyperthyroidism, when present; adverse effects seem infrequent. PMID- 1617801 TI - Re-evaluation of the captopril test for the diagnosis of primary hyperaldosteronism. AB - OBJECTIVE: We aimed to re-evaluate the captopril test in the diagnosis of primary hyperaldosteronism. DESIGN: Serum aldosterone and plasma renin activity were measured supine prior to and 60, 90, 120 minutes after oral captopril, 25 mg. PATIENTS: We have performed this test in ten patients with primary hyperaldosteronism, two with hypertension and secondary hyperaldosteronism and in ten normokalaemic patients with essential hypertension. MEASUREMENTS: Validity was assessed by mathematical prediction methods. RESULTS: Using a ratio of aldosterone to plasma renin activity greater than or equal to 1400 pmol/l per microgram/ml/h as a predictor of primary hyperaldosteronism, the captopril test had a sensitivity of 100%, a specificity of 83% and a predictive value of 82% with a 60-minute post captopril evaluation being sufficient. Nevertheless, this test was only marginally superior to a careful analysis of the supine values where a similar ratio in the presence of a normal or suppressed plasma renin activity predicted primary hyperaldosteronism with a sensitivity also of 100% but a slightly lower specificity of 75% and predictive value of 77%. CONCLUSION: Application of the captopril test to patients identified as abnormal by screening confirms all cases of primary hyperaldosteronism but false positive or equivocal results, necessitating further investigation, may occur in some patients with essential hypertension. PMID- 1617802 TI - Follow-up of ovarian endocrine function in premenopausal women after hysterectomy by daily measurements of salivary progesterone. AB - OBJECTIVE: The effect of hysterectomy on ovarian endocrine function of premenopausal women was studied. DESIGN: The patients collected daily salivary samples during one preoperative cycle (1), the cycle of operation (2), the subsequent period of 30 days (3) and the cycle 6 months after operation (4). PATIENTS: Forty-one premenopausal women (aged 33-48 years) undergoing hysterectomy were studied; their preoperative cycles served as controls. The patients were also compared with a reference group of 17 younger fertile women. MEASUREMENTS: Salivary progesterone levels were measured by radioimmunoassay. RESULTS: Cycle 1 was more frequently short (P less than 0.01), with short luteal phase (P less than 0.01) and low progesterone secretion (P less than 0.05), than the cycles of younger women. Cycle 2 was longer than the other cycles (P less than 0.01), due to prolonged follicular phase (P less than 0.01). Cycle 3 differed from cycle 1 by the lesser frequency of short cycles (P less than 0.01). Cycle 4 and its follicular phase were longer than those measured in cycle 1 (P less than 0.05). Of the women with normal cycle 1, 39% (P less than 0.01) presented with luteal insufficiency (LPD, low luteal progesterone secretion) or anovulation (8%) in at least one of cycles 2 to 4. The frequency of LPD or anovulation was significantly higher in cycle 3 (P less than 0.05) but not in cycle 4, compared to 1. CONCLUSIONS: Acute luteal progesterone deficiency after hysterectomy in premenopausal women is common but in most cases reversible. PMID- 1617803 TI - Determination of bone mineral density by quantitative computed tomography and single photon absorptiometry in subclinical hyperthyroidism: a risk of early osteopaenia in post-menopausal women. AB - OBJECTIVE: There is evidence that treatment with L-thyroxine increases the risk of early osteopaenia. The aim of our study was to investigate the effect of subclinical hyperthyroidism in patients on TSH-suppressive L-thyroxine in view of the increased risk of decalcification. DESIGN: Measurements of bone mineral density were performed in patients with subclinical hyperthyroidism at different scanning sites of varying trabecular portion. Bone mineral values as well as biochemical data were compared to those of normal controls. PATIENTS: Fifty patients (nine men, 25 premenopausal and 16 post-menopausal women) on TSH suppressive doses of L-thyroxine were investigated after removal of thyroid cancer. MEASUREMENTS: Dual energy quantitative computed tomography was used for osteodensitometry in the lumbar spine. Single photon absorptiometry from a 125I source was applied to the calcaneus, midshaft radius and distal as well as proximal scanning sites of the distal radius. Normal bone mineral values for each measurement site were taken from healthy reference populations. RESULTS: A significant decrease of bone mineral density in the calcaneus was found in 26 of 50 patients. Bone mass assessment yielded a 9.1% decrease of mean bone mineral content in all patients compared to controls (P less than 0.01). The decrease in post-menopausal women was 22% (P less than 0.001). In premenopausal women bone mineral density changes in the calcaneus were not statistically significant. Cortical measurement sites like the midshaft radius and the proximal scanning site of the distal forearm showed a 14.8% (P less than 0.05) and 10.8% (P = NS) decalcification in post-menopausal women but normal values at the distal scanning site. The lumbar spine was not affected by subclinical hyperthyroidism in either pre or post-menopausal women. In hypoparathyroid patients, bone density did not essentially differ from normals. There was no significant correlation between bone mineral values and duration of treatment or osteocalcin values. CONCLUSIONS: Our data suggest that TSH suppressive L-thyroxine treatment has a detrimental effect on the appendicular skeleton in post-menopausal women. Additional effects of oestrogen deficiency and subclinical hyperthyroidism might lead to accelerated bone loss requiring close supervision to determine the smallest dose needed for suppression of the pituitary-thyroid axis. PMID- 1617805 TI - Leydig cell hypoplasia leading to two different phenotypes: male pseudohermaphroditism and primary hypogonadism not associated with this. PMID- 1617804 TI - Primary adrenocortical failure masked by exogenous steroid administration. PMID- 1617806 TI - Oculocutaneous diseases I. PMID- 1617807 TI - Human ocular anatomy. AB - An understanding of the anatomy of the eye is the sine qua non for an appreciation of the pathophysiology of ocular disease. This introductory article is a brief review and elucidation of the pertinent aspects of ocular anatomy. Also included is a glossary of opthalmologic terms that may help clarify some of the more esoteric terminology as the reader peruses the various articles in this issue. PMID- 1617808 TI - Cutaneous and ocular ramifications of ultraviolet radiation. AB - In this article,the uses of photobiologic techniques such as ultraviolet B radiation and PUVA are discussed, as is a general review of their potential acute and chronic side effects. The authors then focus, in more extensive detail, on the potential acute and chronic ocular toxicity associated with these modalities. PMID- 1617809 TI - Ocular effects of topical and systemic steroids. AB - Topical and systemic steroids have proven to be invaluable agents in the treatment of a wide range of disorders, but their use is not without potential complications. Before initiation of therapy with systemic steroids, a personal or family history of cataracts, glaucoma, hypertension, diabetes, hyperlipidemia, renal stones, peptic ulceration, and current infection or pregnancy should be ascertained, because these patients have an increased risk of complications. Prior to long-term therapy with systemic steroids, blood pressure measurement, tuberculin skin test, and anergy panel are recommended. Monthly follow-up may include measurements of weight, blood pressure, electrolytes, and blood sugar and guaiac testing of the stool. To prevent the ocular complications of steroid therapy, routine screening is indicated (Table 1). Screening for cataracts, which occur most commonly as a sequela of continuous systemic steroid use, may be performed by slit-lamp examinations conducted three or four times a year for patients on long-term therapy and twice a year for patients taking intermittent topical ocular or systemic steroids. Glaucoma is more often associated with topical ocular or periocular steroids than with systemic steroids; recommended screening includes a baseline intraocular pressure measurement, then routine pressure measurements taken every few weeks initially, then every few months. Ocular rebound inflammation may develop secondary to rapid tapering or abrupt discontinuation of topical ocular steroid use and is best prevented with gradual tapering. Opportunistic infections of the eye include bacterial, viral, and fungal infections and are most often associated with the use of topical ocular steroids. Ophthalmologic evaluation is indicated promptly if patients treated with ocular steroids develop ocular discharge, pain, photophobia, or redness. PMID- 1617810 TI - Antimalarial agents and the eye. AB - Antimalarial compounds have been demonstrated to be both safe and efficacious in the treatment of lupus erythematosus as well as several other dermatologic conditions. It is imperative, however, that physicians familiarize themselves with the potential complications associated with the use of these agents. Furthermore, it is essential that a successful collaborative relationship be developed between the dermatologist and the ophthalmologist who are to treat and monitor the patient to avoid any untoward complications that might afflict the patient. It is important to stress that patients on antimalarial drug therapy be evaluated by an ophthalmologist prior to starting treatment and every 4 to 6 months thereafter. The use of Amsler's grids in compliant patients is recommended. If the patient develops retinal changes consistent with the diagnosis of premaculopathy, then careful consideration should be given to the availability and use of alternative agents. PMID- 1617811 TI - Retinoids and the eye. AB - Systemic retinoids are being used more frequently to treat various disorders of the skin, particularly disorders of keratinization. They are promising agents for chemoprevention of cancer and as such may be widely used in the future. Both natural and synthetic retinoids may affect the eye, both on the surface epithelium and the visual metabolism. Three basic effects of pharmacologic doses of synthetic retinoids have been seen. Blepharoconjunctivitis has been particularly prominent with isotretinoin use. Pseudotumor cerebri has been reported sporadically. Recently, night blindness has been reported with both isotretinoin and fenretinide. The greater use of isotretinoin may be more important in explaining the increased incidence of these side effects than is the individual metabolism of the different available synthetic retinoids. These three major side effects of the eye will be carefully evaluated as newer synthetic retinoids are proposed for further trials. Fortunately, it seems that all of these ocular manifestations are dose dependent and reversible, giving the clinician several alternatives to adjust the treatment regimen. PMID- 1617812 TI - Upper eyelid dermatosis syndrome. AB - UEDS is a complex, fascinating syndrome that, when approached in its totality, can often produce a satisfactory resolution for the patient. Clearly, we have much to learn. PMID- 1617813 TI - Immunobullous diseases with ocular involvement. AB - Collaborative efforts of the dermatologist and ophthalmologist and other physicians with interest and experience in the management of the autoimmune bullous diseases optimize patient care by avoiding potentially harmful delay in diagnosis or implementation of therapy. At our institution, ophthalmologic and dermatologic follow-up visits for patients with bullous disorders involving the eyes are arranged for the same day so that ophthalmic examination and monitoring and adjustment of medication by the dermatologist can be effected. During initiation of treatment, visits are monthly. Later, when patients are stabilized, intervals may be extended to 3 to 6 months. More frequent visits are arranged as needed with the ophthalmologist to manage infectious complications or problems requiring surgical management and with the dermatologist to manage extraocular disease and adverse reactions to medication and to triage concurrent illnesses. PMID- 1617814 TI - Oculocutaneous manifestations of the erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum. AB - Although they were once believed to be distinct diseases, many observers currently consider erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis to represent a mild-to-severe continuum of the same process. Each shares certain clinical, histologic, and etiologic characteristics; among the latter two are frequent ocular involvement. Because long-term ophthalmic sequelae may be catastrophic, early recognition and therapy of this acute oculocutaneous disease spectrum are critically important. PMID- 1617815 TI - Genetic disorders of the skin and eye. AB - This article discusses some of the most uncommon diseases ever seen by the ophthalmologist or dermatologist. Some of these conditions can cause irreparable eye damage if not recognized and treated early after their inception. PMID- 1617816 TI - Ocular and cutaneous manifestations of heritable disorders of collagen and elastic tissue. AB - Ocular and cutaneous stigmata are hallmarks of the heritable disorders of collagen and elastic tissue. Awareness of the oculocutaneous features is essential both to aid diagnosis and to direct management of affected patients. Although the angioid streaks of PXE, blue sclerae of OI, ocular fragility of EDS and ectopia lentis of Marfan syndrome are the best-known ocular signs of these disorders, other relevant ophthalmologic symptoms often accompany such classic findings. PMID- 1617817 TI - Ichthyoses and hyperkeratotic disorders. AB - Many of the ichthyotic disorders have characteristic ocular findings. These disorders include X-linked ichthyosis, lamellar ichthyosis, Sjogren-Larsson syndrome, KID syndrome, Refsum's disease, neutral lipid storage disease, chondrodysplasia punctata, and Richner-Hanhart syndrome. A knowledge of the ocular manifestations may provide a valuable aid to diagnosis in difficult cases. In some cases, knowledge of the ocular complications results in early referral for optimal ophthalmologic care. PMID- 1617818 TI - Ocular manifestations of pigmentary disorders. AB - Disorders of pigmentation can result from either an abnormal number of melanocytes, as in nevus of Ota and vitiligo, or an abnormal amount of melanin production, as in albinism. Melanin-producing cells are found in the skin, mucous membranes, uveal tract, and retinal pigment epithelium of the eye and the stria vascularis of the inner ear. Thus, many of the hereditary or congenital pigmentary disorders of the skin are associated with similar pigmentary abnormalities in the eye, such as iris heterochromia or changes in pigmentation of the fundus; however, more commonly, the associated eye finding is a defect in ocular motility, i.e., strabismus and nystagmus, suggesting a concomitant defect in neurologic development. In albinos, the observed neurologic abnormality in the visual pathway and foveal hypoplasia are hypothesized to be related directly to the lack of melanin in the pigment epithelium during development. In acquired disorders of pigmentation, in particular, vitiligo, Vogt-Koyanagi-Harada syndrome, and onchocerciasis, there is a frequent association with uveitis, suggesting an inflammatory cause for the cutaneous pigmentary changes. PMID- 1617819 TI - Ocular and dermatologic manifestation of neurocutaneous syndromes. AB - The dermatologic and ophthalmologic manifestations of neurocutaneous syndromes are numerous and varied, but familiarity with them is essential to the clinician from any specialty who may have to deal with these disorders. Although many of their complications are unfortunately still difficult or impossible to treat effectively, there may be significant benefit to the patient from prompt detection of optic glioma in NF, retinal angiomas in VHL disease, and glaucoma in SWS. Recognition of characteristic lesions of skin and eye in individuals with mild expressions of NF and TS is essential for genetic counseling. For affected children and their parents, early diagnosis (based on sometimes subtle findings) and formulation of a complete and accurate prognosis can considerably ease the burden imposed by any of these conditions. PMID- 1617820 TI - The value and promise of echocardiography in acute myocardial infarction and coronary artery disease. AB - Two-dimensional and Doppler echocardiography have become extremely useful in the management of patients with acute myocardial infarction (AMI). Echocardiography is noninvasive, relatively inexpensive, and has no known biohazards. It offers unequaled information about cardiac anatomy and function. In the acute setting it is useful in the diagnosis of AMI and its complications. It is an excellent tool for monitoring therapy. Echocardiography has been shown to be useful in risk stratification upon presentation to the emergency ward and prior to hospital discharge. Stress echocardiography has broadened and sharpened the diagnostic and prognostic information. Contrast echocardiography has promise for demonstrating coronary artery flow. Research in ultrasonic myocardial tissue characterization shows potential for differentiating ischemic myocardium from infarcted myocardium. Thus, echocardiography is likely to become increasingly important in the future management of patients with AMI. PMID- 1617821 TI - Effects of captopril on regional segment motion during acute coronary occlusion. AB - The effects of captopril on myocardial segment function in different degrees of transient coronary occlusion were studied using ultrasonic dimension gauges in 15 open-chest dogs. The occlusion procedures (OP) were performed on the left anterior descending coronary artery (LAD) in eight dogs and on the left circumflex coronary artery (Cx) in seven dogs. To measure the changes in segment shortening in the subendocardium we used eight dogs (ischemic and control zones: four dogs LAD and four dogs Cx). To measure the changes in wall thickening we used seven dogs (ischemic and control zones: three dogs LAD and four dogs Cx). Total coronary OP lasting 1 min and partial OP (70-80%) lasting 1 min and 2 min 30 s, before and after captopril (0.25 mg/kg i.v.) were performed. Left ventricular pressure, dP/dt, coronary flow, and ECG were monitored. Total coronary OP (1 min) changed segment shortening (18% LAD; 14% Cx) and wall thickening (19% LAD; 18% Cx) to values of dyskinesis (-3% and -4% for shortening; -6% and -5% for thickening). Captopril improved regional function maintaining positive values for shortening (4% LAD; 3% Cx) and thickening (0.3% LAD; 4% Cx). Similar responses were obtained during partial OP and captopril. Results suggest that captopril produced a significant improvement in the regional function parameters affected by ischemia both in total and partial obstructions. PMID- 1617822 TI - Comparative effects of pravastatin and lovastatin on nighttime sleep and daytime performance. AB - Pravastatin and lovastatin, two HMG-CoA reductase inhibitors with similar cholesterol-lowering effects, differ in their lipid solubility. The hydrophilic characteristics of pravastatin may explain why the drug has not been detected in cerebrospinal fluid. On the other hand, lovastatin, a lipophilic compound, has been detected in the cerebrospinal fluid. Previous reports have suggested that lovastatin administration may be associated with insomnia, which reflects an action in the central nervous system. The effects of the two drugs on nocturnal sleep and day-time performance in young, healthy men have been assessed in randomized, double-blind, placebo-controlled studies. Computer-based performance tests were administered on two consecutive days before drug administration and at the end of a 3-week active drug or placebo treatment period. Results from both sites were combined for analysis. Neither pravastatin nor lovastatin significantly affected nocturnal sleep or daytime sleepiness in this study population, but lovastatin significantly affected daytime performance. In subjects treated with lovastatin, the results showed that two measures of performance, divided attention (p less than 0.05) and vigilance (p less than 0.01), worsened significantly from baseline as did global performance (p less than 0.01). Performance was not affected in the pravastatin and placebo groups. These results provide preliminary evidence of an adverse effect of lovastatin on daytime performance. PMID- 1617823 TI - Myocardial systolic function in systemic lupus erythematosus: a study based on radionuclide ventriculography. AB - We assessed left ventricular systolic function by means of radionuclide ventriculography in 20 consecutive unselected patients with systemic lupus erythematosus. All patients had normal left ventricular systolic function (defined as ejection fraction greater than 45%) in a resting state. Regional wall motion abnormalities were, however, seen in 4 patients (20%). Of these 20 patients, 8 were able to exercise on a bicycle ergometer. These patients were subjected to exercise radionuclide ventriculography. Of these 8 patients, 3 (37.5%) had an abnormal ventriculographic response to exercise (as evidenced by a subnormal rise in ejection fraction or a fall, appearance of a new regional wall motion abnormality or worsening of a pre-existing one). This probably reflects subclinical left ventricular dysfunction unmasked by the stress of exercise. The clinical significance of these abnormalities on long-term myocardial function and their possible reversibility with remission of the disease needs to be assessed in future studies. PMID- 1617824 TI - Coronary heart disease risk factors in Hansen's disease sufferers. AB - In the frame of an epidemiologic study of Hansen's disease (HD) sufferers, several risk factors have been investigated which might explain the high prevalence of coronary heart disease (CHD) among HD patients. The data analyzed in the present study are derived from 293 HD patients (157 men and 136 women). The patients, after having completed a WHO adopted questionnaire, were given a complete physical examination, a resting and an exercise electrocardiogram, and biochemical as well as hematological examinations. Coronary HD patients, when compared to noncoronary HD patients, showed statistically significant differences in the following parameters: (1) mean age, (2) mean concentration of the electrophoretic fraction of alpha-lipoproteins, (3) deviation from mean weight, (4) prevalence of hypertension, and (5) prevalence of the borderline lepromatous form of HD. However, the differences found when comparing other parameters, such as blood pressure, smoking, diabetes mellitus, total cholesterol, triglycerides, pre-beta and beta-lipoproteins, uric acid, erythrocyte sedimentation rate, ABO blood groups, etc., did not reach the level of significance. These findings suggest that HD sufferers are a special population subgroup with reference to CHD risk factors, differing in many ways from the general population. PMID- 1617825 TI - Direct current cardioversion of established atrial fibrillation. AB - Restoration and maintenance of sinus rhythm is a desirable end point in patients with chronic atrial fibrillation. If clinically indicated, external cardioversion using direct current is the method of choice in most centers. The results range from 20 to 90% and are highly influenced by the underlying etiology. A number of determinants including age, duration of atrial fibrillation, and size of left atrium are usually taken into account in the indications but have been recently questioned. The use of prophylactic antiarrhythmic therapy has been shown to reduce the recurrence of atrial fibrillation significantly, but concerns remain regarding the safety of this treatment. In patients who failed external cardioversion, shocks delivered within the right atrium according to a recently described technique may be attempted. The initial results are promising, as 83% of patients are successfully cardioverted and 46% of patients are in sinus rhythm at 12 months. This new technique offers an additional alternative in patients with chronic atrial fibrillation and may therefore reduce the incidence of frightening embolic complications. PMID- 1617826 TI - Anatomy, histology, and pathology of coronary arteries: a review relevant to new interventional and imaging techniques--Part I. AB - In the last 15 years, intense interest has focused on various interventional pharmacologic and mechanical forms of therapy for the treatment of atherosclerosis coronary artery disease. Many techniques and devices (dilating balloons, perfusion catheters, thermal probes and balloons, lasers, atherectomy devices, stents, intravascular ultrasound) have been used or are under study for future use. Many of these techniques and devices require an understanding of histologic and pathologic features of the coronary arteries and diseases which affect them. This article reviews selective areas of anatomy, histology, and pathology relevant to the use of various new interventional techniques. Part I of this review will focus on anatomic aspects of the epicardial coronary artery system, coronary arterial distribution, myocardial supply, and histologic features of the normal coronary artery. PMID- 1617827 TI - Isolated left main coronary stenosis and mediastinal irradiation. AB - This report draws an association between mediastinal irradiation and isolated left main coronary artery stenosis. The report highlights two patients who developed selective left main coronary artery stenosis post mediastinal treatment. In the animal model, it has been shown that high serum cholesterol levels at the time of, or soon after, irradiation are necessary to initiate arteriosclerotic plaque formation. PMID- 1617828 TI - Use of transesophageal echocardiography to visualize an anomalous right coronary artery arising from the left main coronary artery (single coronary artery). AB - This case report demonstrates a role for transesophageal echocardiography in defining the course of anomalous coronary arteries. Origin of the right coronary artery (RCA) from the left main (LM) (single coronary artery) is an exceedingly rare congenital anomaly. It is not always benign and may result in myocardial infarction. This may be due to compression between the aorta and the pulmonary artery. Transesophageal echocardiography offers a low-risk, noninvasive means of imaging the proximal coronary arteries. In the majority of patients, the proximal segments of the three major coronaries can be clearly visualized. With the addition of color flow, it is possible to visualize flow in most patients. Proximal obstructive lesions can be seen in some patients although sensitivity thus far seems low. PMID- 1617829 TI - Anomalous origin of left coronary artery from the pulmonary artery: evolution of left ventricular function and perfusion after surgery in a 44-year-old man. AB - Anomalous origin of left coronary vessel from the pulmonary artery is an almost universally fatal form of congenital heart disease unless appropriate corrective surgery is performed at an early age. A case was diagnosed in a symptomatic 44 year-old man who presented an impairment of systolic left ventricular function. The abnormality was successfully treated with ligation of the left coronary artery combined with left internal mammary artery anastomosis. Left ventricular function improved dramatically six months after surgery, both at rest and during exercise. Such an evolution suggests that surgery may be indicated not only in infants but also in adults with this congenital heart abnormality. PMID- 1617830 TI - Ventricular tachycardia of right bundle-branch block--left axis deviation morphology and organic heart disease. AB - Most series of patients with ventricular tachycardia (VT) of right bundle-branch block (RBBB)-left axis deviation (LAD) morphology include young individuals with no overt evidence of structural heart disease. In the present report, the clinical and electrophysiologic findings in two patients with verapamil responsive VT and organic heart disease are described. PMID- 1617831 TI - Samuel A. Levine (1891-1966). PMID- 1617832 TI - Immunotherapy of mammary adenocarcinoma metastases in C3H/HeN mice with chronic administration of cyclo-oxygenase inhibitors alone or in combination with IL-2. AB - In this study the efficacy of treatment of two cyclo-oxygenase inhibitors, ibuprofen (Ibu) and indomethacin (Indo), are compared in the immunotherapy of metastasis designed to reverse prostaglandin E2 (PGE2)-mediated inactivation of interleukin-2 (IL-2)-dependent host killer cell lineages. These agents were tested either alone for the prevention of metastasis or in combination with IL-2 for the eradication of established metastasis. C3H/HeN mice were placed on chronic oral Ibu (CIbT; 200 and 600 micrograms/ml of water) or Indo (CIT; 10 micrograms/ml) 5 days after s.c. transplantation of 5 x 10(5) metastatic C3L5 mammary carcinoma for the prevention of spontaneous lung metastases. They showed intolerance to Indo at a dosage of 14 micrograms/ml, which was well tolerated by other mouse strains in previous studies, but tolerated the Ibu dosages used. Control and treated mice were killed on day 30 to score metastatic lung colonies, to evaluate killer activity in splenocytes against natural killer (NK)-sensitive YAC-1 lymphoma or NK-resistant C3L5 adenocarcinoma and 8911 lymphoma targets, and to phenotype the surface markers of killer cells. CIbT and CIT alone at the above dosage significantly reduced the number of lung colonies, retarded local tumor growth and restored NK activity of splenic killer cells expressing AGM-1+, Thy-1 , Lyt-2- phenotype. To treat established lung metastasis, mice bearing 15-day C3L5 transplants were given CIbT or CIT alone or in combination with two 4-day rounds (days 20-23, 31-34) of IL-2 (15,000 Cetus units, i.p. every 8 h) and were killed on day 35 to score lung colonies and characterize splenic killer cells. CIbT or CIT alone reduced the number of spontaneous lung metastases and restored anti-YAC-1 killer function of splenocytes with NK-like phenotype (AGM-1+, Thy-1-, Lyt-2-); some anti-C3L5 killer function was also generated in the high dose Ibu group and the killer cell showed AGM-1+, Thy-1+ and Lyt-2+ phenotype. Combined therapies with CIbT or CIT plus IL-2 were more effective in reducing metastases and promoting killer cell function, the best results being achieved with high dose Ibu+IL-2. All killer cells expressed AGM-1 and Thy-1. In addition, C3L5 killer cells also expressed Lyt-2, suggesting T-cell stimulation. PGE2 synthesis in the host was inhibited by at least 50% in mice subjected to CIbT or CIT.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1617833 TI - Metastasizing lung carcinomas in Hann: Wistar rats. AB - In Hann:Wistar rats, 25 weekly subcutaneous injections of dipentylnitrosamine (DPNA) at doses of 0, 62.5, 125 and 250 mg/kg body weight induced lung carcinomas which metastasized partly. The incidence of the primaries was 2.5, 20.0, 77.5 and 100% in the males and 0, 0, 12.5 and 57.5% in the females, respectively. The frequency of metastases was 0, 12.5, 38.7 and 72.5% in the males and 0, 0, 40.0 and 52.2% in the females, respectively. The most common metastatic sites in males and females together were: lung-associated lymph nodes (82.1%), adrenal gland (53.6%), kidney (39.3%), pancreas (32.1%), bones (16.1%), heart (12.5%), mesentery (12.5%) and CNS (8.9%). In the females, metastases were also detected in the uterus (21.4%) and ovary (42.9%). The results indicate that: (1) through subcutaneous injections of DPNA metastasizing lung carcinomas can be induced with high incidence, and (2) the metastatic pattern is very similar to human cases. Thus, this model could be useful for the study of metastasizing lung carcinomas in experimental animals. PMID- 1617834 TI - A YIGSR-containing novel mutein without the detrimental effect of human TNF-alpha of enhancing experimental pulmonary metastasis. AB - The injection of B16F10 melanoma cells with recombinant human tumor necrosis factor alpha (TNF-alpha) into the tail vein of C57BL/6 mice resulted in 2- to 25 fold more metastatic foci in the lungs than the injection of tumor cells alone. Clearly, TNF-alpha significantly enhanced experimental tumor metastasis. Furthermore, it enhanced the metastasis of Lewis lung carcinoma cells. In contrast, a mutein of TNF-alpha, designated as F4236, having the cell-adhesive sequence (Tyr-Ile-Gly-Ser-Arg) at the N-terminus of the TNF molecule did not enhance metastasis, but rather exhibited similar antitumor activity to wild-type TNF-alpha in fibrosarcoma-bearing mice. PMID- 1617835 TI - Na[trans-RuCl4(DMSO)Im], a metal complex of ruthenium with antimetastatic properties. AB - The antitumor and antimetastatic effects of a ruthenium(III) complex, Na[trans RuCl4(DMSO)Im], have been examined in mice bearing MCa mammary carcinoma. Na[trans-RuCl4(DMSO)Im] is capable of reducing primary tumor growth and of prolonging the survival time with different schedules of administration. However, better effects were obtained (a) with treatments started soon after tumor implantation, (b) with daily administration rather than with treatments at 4-day intervals and (c) using relatively low daily doses. The prolongation of survival time in tumor-bearing hosts, greater than that obtained with cisplatin, cannot be simply related to the effect on primary tumor growth, always less than that of cisplatin. Rather, emphasis is placed on the reduction of lung metastasis formation, obtained either by i.v. injection of tumor cells (lung colonization or spontaneously from i.m. tumor implants, which is significantly greater than the reduction of primary tumor growth. The antimetastatic effect depends on the treatment schedule and is greater with low doses given daily than with high doses administrated with drug-free intervals. Metastasis reduction involved mainly large metastatic nodules, reducing the average weight of each metastasis by 8 fold for spontaneous metastases and by 5-fold for lung colonies. The antimetastatic action of Na[trans-RuCl4(DMSO)Im] thus indicates the possibility that related analogs can represent a new generation of antitumor compounds capable of selectively interacting with metastasis formation of solid tumors. PMID- 1617836 TI - Esophageal dysmotility as a serendipitous observation on ventilation-perfusion imaging of the lungs. AB - Tc-99m DTPA aerosol is often swallowed during inhalation for lung ventilation scans. The authors evaluated a 16-year-old girl with a known history of mixed collagen disorder (positive lupus anticoagulants) for symptoms of cough and acute shortness of breath. Tc-99m DTPA accumulated in the distal esophagus during aerosol inhalation and remained there at the end of the perfusion study, a period of approximately 1 hour. This serendipitous observation antedates clinical signs and symptoms of dysphagia. PMID- 1617837 TI - High-resolution bone scintigraphy of the adult wrist. AB - Bony anatomic landmarks of the wrist (e.g., pisiform, hook of hamate, radioulnar joint, and styloid processes of the radius and ulna) were routinely identified in 28 adult patients examined for wrist pain. With the wrists prone and immobilized, bone scintigrams were obtained for 500,000 counts with an asymmetric (133 to 161 keV) Tc-99m energy window and either a converging (best choice) or straight-bore, high-resolution collimator. High-resolution scintigraphy precisely localized degenerative joint disease (nine patients), scaphoid fractures (five), pisiform fracture (one), lunate avascular necrosis (one), radioulnar arthritis (one), septic or inflammatory arthritis (six), ulnocarpal impingement (two), and reflex sympathetic dystrophy syndrome (two). Images obtained palm down with the wrist in ulnar deviation helped identify increased uptake within the scaphoid. Fracture and significant bone or joint disease were excluded in one patient. PMID- 1617838 TI - Evaluation of sensitivity and specificity of upper extremity radionuclide venography in cancer patients with indwelling central venous catheters. AB - Two hundred twenty upper extremity radionuclide venograms were performed using upper extremity injection of 5 mCi of Tc-99m DTPA in each arm of patients with indwelling central lines. Evidence of obstruction was found in 123 patients, collateral flow without anatomic obstruction in six patients, and a slow-flow pattern in 12 patients. Twenty-six of these also underwent upper extremity contrast venography within 48 hours of the scan. Contrast venograms and radionuclide venograms agreed in 19 patients (16 correctly identified as obstructed, three correctly identified as unobstructed). Six patients showed the slow-flow pattern without collaterals or obstruction. Subsequently, six follow-up contrast studies showed no evidence of obstruction or collaterals. The authors conclude that obstruction with collateral flow on radionuclide venograms correctly predicts obstruction. However, the slow-flow pattern does not and should not be used as the sole criterion to diagnose partial obstruction. PMID- 1617839 TI - Comparison of Tl-201 renal uptake with Tc-99m DTPA angiorenography in patients with hypertension. Measures of renal asymmetry. AB - Renal uptake of Tl-201 reflects renal perfusion and may have a role in defining renal asymmetry in patients with hypertension who are referred for myocardial scintigraphy. The authors compared two methods of quantitating differential renal uptake of Tl-201, with similar data obtained from the angiographic and renal uptake (RU) phases of Tc-99m DTPA scintigraphy in 35 patients with hypertension. For Tl-201, asymmetry in renal counts was quantitated based on a simple outline technique or on interpolative background subtraction of 5-minute posterior images. Inter-observer and intra-observer variability among duplicate measurements were lower for Tl-201, particularly with interpolative background subtraction, than for Tc-99m DTPA. Renal/background ratios were similar for Tl 201 and RU-phase Tc-99m DTPA images when considering liver, spleen, or inter renal regions as background; however, paraspinal uptake was relatively higher with Tl-201 (P less than 0.01). Qualitatively, renal asymmetry scores with the two radiotracers agreed (r = 0.89, blinded readings by four observers), although asymmetry was more marked with Tl-201 (P = 0.06). Measurements with Tl-201 agreed with both phases of Tc-99m DTPA (r = 0.96 to 0.98), but interpolative background subtraction systematically yielded greater inter-renal asymmetry than RU (P less than 0.01), reflecting the qualitative impression. Thus, ancillary Tl-201 imaging reflects differences between the kidneys in a fashion similar but not identical to Tc-99m DTPA scintigraphy. PMID- 1617840 TI - Tc-99m DTPA and I-131 hippurate renography. Findings in hepatorenal syndrome. AB - Tc-99m DTPA and I-131 OIH renography were performed simultaneously in a patient with hepatorenal syndrome. Blood flow was delayed and diminished bilaterally; there was Tc-99m DTPA and I-131 OIH retention in the parenchyma with no evidence of tracer retention in the collecting systems. The I-131 OIH renogram curve demonstrated a steadily rising pattern, whereas the Tc-99m DTPA curve demonstrated an initial vascular peak and was subsequently flat. There was no appreciable response to furosemide. These findings are not specific for hepatorenal syndrome, and the diagnosis is based on the characteristic clinical setting and the exclusion of other causes of renal failure. A brief literature review and a discussion of differential diagnosis are included. PMID- 1617841 TI - 'Reverse crescent pattern' on SPECT brain perfusion scan in chronic subdural hematoma. AB - A SPECT brain perfusion scan was performed on a patient who had symptoms of dementia. The SPECT scan showed marked crescentic medial displacement of the left cerebral hemisphere ("reverse crescent pattern"), and mildly decreased cortical perfusion in the affected hemisphere. Crossed cerebellar diaschisis was not present. On x-ray CT, the underlying abnormality was found to be a unilateral chronic subdural hematoma causing a significant mass effect. A reverse crescent pattern without crossed cerebellar diaschisis on SPECT brain perfusion scan in patients with dementia may suggest the diagnosis of chronic subdural hematoma. PMID- 1617842 TI - Identification of hypometabolic areas in the brain using brain imaging and hyperbaric oxygen. AB - Current neurologic assessments consider idling neurons and ischemic penumbras to be metabolically lethargic and electrically nonfunctional or nonviable. Diagnosis, prognosis, and therapeutics of central nervous system dysfunctions require differentiation between viable and nonviable neurons. It is necessary to develop and document efficacious and safe techniques for reactivating idling neurons. The authors present a case study of a near drowning 12 years earlier. Areas of cortical hypometabolism were identified by using SPECT imaging in conjunction with hyperbaric oxygen therapy (HBOT). Delayed imaging after HBOT (1 hour, 1.5 atm abs) suggested viable but metabolically lethargic neurons. After HBOT (80 1-hour treatments, monoplace chamber, 1.5 atm abs), marked improvements in cognitive and motor functioning were demonstrated. The data support the hypothesis that idling neurons and ischemic penumbras, when given sufficient oxygen, are capable of reactivation. Thus, changes in tracer distribution after a single exposure to HBOT may be a good prognostic indicator of viable neurons. HBOT may be valuable not only in recovery from anoxic encephalopathy but also from other traumatic and nontraumatic dysfunctions of the central nervous system, including stroke. HBOT in conjunction with physical and rehabilitative therapy may help reactivated idling neurons to remain permanently active. PMID- 1617843 TI - Imaging of regional spread of breast cancer by internal mammary lymphoscintigraphy, CT, and MRI. AB - Forty women with breast cancer underwent imaging by internal mammary lymphoscintigraphy (IMLS), which was correlated with the results of CT and MRI of the chest. IMLS was performed and interpreted using the previously described methods of Ege. It identified 22 instances of ipsilateral internal mammary nodal involvement, none of which corresponded to cases of abnormally enlarged (diameter greater than 1.0 cm) internal mammary nodes on CT and/or MRI. Positive IMLS was associated with axillary nodal metastases in 15 out of 22 instances. The authors conclude that IMLS provides information on regional nodal spread of breast cancer that is not available with either CT/MRI imaging or axillary biopsy. PMID- 1617844 TI - Serendipitous scintigraphic detection of asymptomatic anastomotic pseudoaneurysms in human pancreatic allografts. AB - Two cases of scintigraphically detected asymptomatic graft anastomotic pseudoaneurysms are reported. Both patients previously underwent simultaneous renal and pancreatic transplantation. The role of imaging in the diagnosis of this relatively rare, but potentially lethal, vascular complication of pancreatic transplantation is discussed. This is the first report of anastomotic pseudoaneurysms in pancreatic transplants being diagnosed by scintigraphy. PMID- 1617845 TI - Significance of increased Tl-201 uptake by the lungs in patients undergoing oral dipyridamole-thallium myocardial imaging. AB - The purpose of this study was to evaluate the significance of increased Tl-201 uptake by the lungs after oral dipyridamole testing. In conjunction with myocardial perfusion scintigraphy, intravenous dipyridamole has been recently approved as an alternative to exercise for the evaluation of coronary artery disease in patients who cannot adequately exercise, and it will largely replace oral dipyridamole testing. This study contributes to the understanding of the significance of increased lung thallium uptake during pharmacologic stress testing. Oral dipyridamole, 400 mg, was administered to 192 patients undergoing Tl-201 imaging for clinical indications. Mild adverse effects occurred in 31% of patients (chest pain, nausea, headache, or flushing). Dipyridamole had minimal hemodynamic effects. The lung/heart thallium activity ratio was determined in 152 patients. These were subdivided into four groups according to the presence or absence of ischemia, transient myocardial perfusion defect, or scar as indicated by a fixed myocardial perfusion defect. In 61 patients without transient myocardial perfusion defect or fixed myocardial perfusion defect (group 1), the lung/heart thallium activity ratio was 0.39 +/- 0.01 (mean +/- SEM). In 31 patients without transient myocardial perfusion defect but with fixed myocardial perfusion defect (group 2), the lung/heart thallium activity ratio was higher, 0.44 +/- 0.02 (P less than 0.05). In 27 patients with transient myocardial perfusion defect but no fixed myocardial perfusion defect (group 3) and in 33 patients with both transient myocardial perfusion defect and fixed myocardial perfusion defect (group 4), the lung/heart thallium activity ratio was 0.51 +/- 0.03 and 0.52 +/- 0.03, respectively, both significantly higher than either group 1 or group 2 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617846 TI - An unusual presentation of carcinoid tumor metastatic to bone. PMID- 1617847 TI - A novel cause of Ga-67 localization. Subclinical myopathy after conventional exercise. PMID- 1617848 TI - Stunned thyroid after high-dose I-131 imaging. PMID- 1617849 TI - Pseudotumor of the liver caused by pectus excavatum as seen on sulfur colloid scintigraphy. PMID- 1617850 TI - Three-phase bone scintigraphy in Maffucci's syndrome. PMID- 1617851 TI - Ga-67 imaging of amiodarone pulmonary toxicity with pseudocavitary lung lesion. PMID- 1617852 TI - Pulmonary gallium photopenia from oligemia. PMID- 1617853 TI - Skeletal scintigraphy. Radiographic artifacts. PMID- 1617854 TI - False-positive Tl-201 SPECT studies in patients with left bundle branch block: frequency and clinical significance. PMID- 1617855 TI - Pharmacokinetic and pharmacodynamic data collection in children and neonates. A quiet frontier. PMID- 1617856 TI - Pharmacokinetic studies in paediatric patients. Clinical and ethical considerations. AB - Important advances in paediatric clinical pharmacology have been made over the past 2 decades. However, there remains a reluctance to pursue pharmacodynamic and pharmacokinetic studies in children and, consequently, many important therapeutic agents have not been adequately studied in this population. Age-related pharmacokinetic/pharmacodynamic studies are not only essential to provide optimal drug therapy for children, but are quite feasible. Usually, paediatric pharmacokinetic studies are conducted in children receiving treatment for a specific medical condition. The approach to soliciting participation of paediatric subjects requires special sensitivity to the fears and anxieties of the child and the parents. Factors influencing subject enrollment and suggestions to enhance enrollment into study protocols are discussed. Pharmacokinetic/pharmacodynamic studies require repeated measurements over time and often entail obtaining multiple blood and urine samples. Techniques for reducing sample volume and number of necessary samples while minimising the discomfort and fear associated with obtaining multiple samples include the development of highly sensitive analytical methods to measure drug concentrations in small volume samples. The number of samples obtained from individual subjects can be minimised by using pharmacokinetic analytical approaches such as the nonlinear mixed effect model (NONMEM) which allows estimation of pharmacokinetic characteristics of a population using limited data from each subject. In addition, less invasive methods to measure drug metabolism/elimination such as salivary sampling, transcutaneous collection and breath analysis have been applied to the study of certain drugs. Children are a particularly vulnerable population because of their limited cognitive abilities and dependence on adults. Thus, they must be afforded greater protection from exploitation as research subjects than that provided to adults. PMID- 1617857 TI - Intranasal insulin. Clinical pharmacokinetics. AB - Insulin administered nasally has considerable potential for the treatment of both insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes. For patients with NIDDM it is possible to prevent preprandial hyperglycaemia and postprandial hypoglycaemia by employing a suitable and properly timed intranasal insulin dose. The low bioavailability of simple formulations of insulin can be greatly improved by using absorption enhancers or novel delivery systems such as bioadhesive microspheres. The need for nontoxic and nonirritant systems is stressed. PMID- 1617859 TI - Population pharmacokinetics of gentamicin. Use of the nonparametric expectation maximisation (NPEM) algorithm. AB - A new nonparametric expectation maximisation (NPEM) algorithm for the estimation of population pharmacokinetic parameter values was evaluated. The algorithm, in the form of a personal computer program, was used to compute population pharmacokinetic parameter densities of gentamicin in a group of 9 patients with indicators of malnutrition. The 1-compartment parameter values for clearance (CL), volume of distribution (Vd) and elimination rate constant (k) were compared with values generated using a standard 2-stage (STS) approach. NPEM was used with a full data set (72 gentamicin concentrations) and a sparse data set (only peak and trough concentrations for each patient; 18 in total). There were no differences in parameter value estimations between the STS and NPEM with all the data (p greater than 0.05) or with the sparse data (p greater than 0.05). Mean parameter value estimates from the STS and NPEM (with sparse data) were used as a priori data sets in the USC*PACK gentamicin Bayesian program to predict concentrations in 8 subsequent patients with similar indicators of malnutrition. There were no differences in predicted gentamicin concentrations between STS (3.75 +/- 2.06 mg/L) and NPEM (3.75 +/- 2.17 mg/L). NPEM was able to generate population pharmacokinetic parameter values for gentamicin in a defined population of patients using sparse routine clinical data. It was also shown to function with only a single data point per patient. PMID- 1617858 TI - Pharmacokinetics and therapeutic efficacy of retinoids in skin diseases. AB - The retinoids are a class of compounds that includes the natural forms and synthetic analogues of vitamin A. Isotretinoin, often referred to as a first generation retinoid, may be of considerable benefit to patients with severe, recalcitrant acne. Etretinate and acitretin, 2 aromatic compounds representing the second generation, have found their major success in the treatment of psoriasis, particularly in combination with more traditional therapies. Retinoid therapy is associated with a distinctive adverse effect profile typical of hypervitaminosis A; thus, it is especially important that fertile women undergoing retinoid therapy adhere to a contraceptive regimen. These drugs are extensively metabolised and only traces of unchanged drugs are eliminated in urine. The terminal elimination half-lives of isotretinoin, etretinate and acitretin after long term treatment are up to 20h, 120 days and 48h, respectively. Because of lack of definite correlation between plasma concentration and desired pharmacological effects, in conjunction with the very pronounced inter- and intraindividual variation in systemic availability (15 to 90%) after oral administration of these drugs, initial dosages in individual patients can only be roughly judged on the basis of the general pharmacokinetics of the agents. Later dosage adjustments should be made on the basis of monitoring of both plasma drug (and possible metabolite) concentrations, and the efficacy and tolerability of the drugs. PMID- 1617860 TI - Evaluation of hepatic function using the pharmacokinetics of a therapeutically administered drug. Application to the immunosuppressant cyclosporin. AB - A method is presented for the simultaneous estimation of functional hepatic blood flow and intrinsic clearance. The method uses pharmacokinetic data of a therapeutically employed drug and one of its primary metabolites following intravenous and oral administration of the parent compound. When the disposition of the drug is linear, this method can cope with complicated dosage regimens commonly confronted in clinical data. The feasibility of the method was demonstrated in 10 patients who had undergone liver transplantation and were receiving cyclosporin in the immediate postoperative period. Mean hepatic blood flow was estimated to be 0.89 (95% CI: 0.62 to 1.23) L/h/kg and intrinsic cyclosporin clearance as 0.60 (95% CI: 0.49 to 0.72) L/h/kg. Apart from the hepatic parameters, bioavailability and the fraction of the dose absorbed, a detailed pharmacokinetic description of the parent drug and the elimination pharmacokinetics of a primary metabolite are provided. This information not only allows optimisation of individual therapy, but also may be used to compare absorption properties of different pharmaceutical formulations. PMID- 1617861 TI - CaEDTA vs CaEDTA plus BAL to treat children with elevated blood lead levels. AB - The effectiveness of CaEDTA alone vs CaEDTA plus BAL was compared retrospectively in a group of 72 children with lead levels between 2.41 mumol/L (50 micrograms/dL) and 2.90 mumol/L (60 micrograms/dL). The children who received both drugs had higher median zinc protoporphyrin (ZnP) concentrations at the initiation of therapy than children who received CaEDTA alone (160 micrograms/dL vs 96 micrograms/dL, p less than .01). There was a significantly increased incidence of vomiting and abnormal liver-function test results in the children who received both drugs. The children who received CaEDTA alone had a greater percent mean fall in lead level at one to three weeks postchelation (30.5% vs 18.1%, p less than .05). Children who received both CaEDTA and BAL had a greater percent decrease in ZnP at four to eight months postchelation, but there was no difference in percent decrease in lead levels. Children who received both drugs also had a greater number of repeat courses of chelation by six months. The addition of BAL to CaEDTA for treatment of children with lead levels of 2.41 mumol/L (50 micrograms/dL) to 2.90 mumol/L (60 micrograms/dL) produced greater toxicity and does not seem to prevent repeat chelations within six months. PMID- 1617862 TI - Predicting length of hospitalization of sick neonates from their initial status. AB - It has been suggested that the estimated date of confinement (EDC) may be used to predict the length of hospital stay for sick newborns. We have found this method unreliable and designed the following study to develop a mathematical model to predict length of stay (LOS). We reviewed the records of 393 neonates. Statistical analysis was performed using multiple linear regression. The factors that reached statistical significance were birth weight (BW), gestational age (GA), and a combined respiratory score (RES). The RES was developed to quantify the degree of initial respiratory illness. Through this model we developed the following formula: log(e) (LOS) = 4.395-0.023 (GA) -0.00054(BW) + 0.0274 (RES). The R value is 0.78. The model predicts an LOS +/- 10 days in 73% of cases. Overall, this model yields a 29% improvement in predictability of LOS compared with a model which used EDC only. This formula may provide useful information for parents and caregivers of hospitalized neonates. PMID- 1617863 TI - Effect of dietary aspartame on plasma concentrations of phenylalanine and tyrosine in normal and homozygous phenylketonuric patients. AB - Six normal subjects each ingested a single 12-oz can of a diet cola (Diet Coke) providing 184 mg aspartame (APM), of which 104 mg is phenylalanine (Phe), and, on another occasion, a single 12-oz can of regular cola (Coke Classic). Neither cola significantly affected plasma concentrations of Phe or tyrosine over the three hour postingestion study period. Each of five homozygous phenylketonuric (PKU) subjects (ages 11, 16, 17, 21, and 23 years) ingested a single 12-oz can of the same diet cola. In these five subjects (three with classic PKU and two with hyperphenylalinemia), the increase in plasma Phe concentrations varied from 0.26 mg/dL to 1.77 mg/dL two or three hours after ingestion (baseline levels, 5.04 to 17.2 mg/dL). Tyrosine concentrations did not differ significantly from baseline levels. The data indicate that ingestion of dietary Phe, as supplied in a single can of diet cola, is readily handled in both normal and PKU subjects. The small increases in plasma Phe concentrations in the homozygous PKU patients are not considered clinically significant. PMID- 1617864 TI - Improving resources for foster care. AB - The number of foster children and their psychological and medical morbidity are growing. To gain insight into how to recruit and retain foster homes, characteristics of 64 foster families were determined by interview. Foster parents had low-to-moderate incomes, were approaching middle age, had underutilized home space, and wanted more children. Most enjoyed foster care and planned to continue. Twenty-three percent of the 64 had half of all foster children in the study in their homes at interview and had cared for seven times as many children in the past, including 66% of all the teens and 83% of all the handicapped children who had been in the 64 homes. These "high providers" functioned like group homes for mentally handicapped individuals. Adapting the group-home concept to foster homes could improve care, especially for children with special needs. PMID- 1617865 TI - Interobserver variability in assessing pediatric postextubation stridor. AB - The reliability of parameters used to assess pediatric postextubation upper respiratory distress is unknown. We prospectively studied the interobserver reliability of six parameters commonly used to assess respiratory distress in children. Eligible patients were less than 15 years old and hospitalized for traumatic injuries at Harborview Medical Center between March and September 1989. At extubation, patients were examined independently by a physician, a nurse, and a respiratory therapist, each of whom evaluated respiratory rate (RR), stridor, air movement, flaring/retractions (F/R), level of consciousness (LOC), and oxygen saturation (O2 sat). Reliability was measured by percentage agreement and weighted kappa (Kw). The 25 children (27 extubations) had a median age of 7 years, and eight of the 27 required treatment for upper airway obstruction. Percentage agreement ranged from 82% (for air movement) to 96% (for O2 sat). Weighted kappas were excellent for RR and F/R (Kw greater than .6); moderate for LOC, stridor, and O2 sat (0.4 less than Kw less than .06); and poor for air movement (Kw less than .4). Further improvements in interobserver agreement are required to provide more consistent upper airway management in critically ill children. PMID- 1617866 TI - Chronic nonspecific diarrhea of childhood. PMID- 1617867 TI - The role of bicycle helmets in bicycle-related injury prevention. PMID- 1617868 TI - Hypocalcemia as the initial manifestation of occult cholestatic liver disease. PMID- 1617869 TI - Cerebral cavernous angiomas in the newborn. PMID- 1617870 TI - Localized meningoencephalitis and group A streptococcal bacteremia. PMID- 1617871 TI - Intervertebral disc calcification. PMID- 1617872 TI - Antibiotic dosages in the treatment of group A streptococcal infections. PMID- 1617873 TI - Anisometropic amblyopia: an easily overlooked cause of visual loss in children. PMID- 1617874 TI - Prevention of prematurity. PMID- 1617875 TI - Prematurity prevention: who is at risk? AB - Previous preterm birth, previous preterm labor, regular uterine activity, uterine distention, and preterm cervical change are factors that are most often present in patients treated for preterm labor or in patients delivered prematurely. In addition to their frequency, their severity is also the highest in terms of patient risk. These factors usually are easily identified, and an appropriate management plan can be implemented to decrease the incidence of preterm births or to at least increase the fetal time in utero. Antenatal bleeding, chronic urinary tract infections, smoking, and maternal age are also associated with preterm labor. Although these factors are not present as often, they have the potential to precipitate preterm labor and preterm delivery. When they are identified, it is necessary to utilize the appropriate therapeutic measures commensurate to the number and/or the degree of the risk factors. Vaginal microbiology, maternal hematocrit, substance abuse, and coitus are factors that are undergoing active investigation in regards to precipitating preterm birth. They are frequently seen in normal pregnancies, but recently have been associated with a greater likelihood for preterm labor and preterm birth. Unequivocal evidence of this association is currently unavailable; however, more and more investigations are reporting a significant association of these factors with preterm births. The relative degree of risk and the optimal management plans for dealing with these factors also await further definition and refinement. We know that there is no surveillance technique, or combination of techniques, that will identify all patients who will eventually deliver preterm. In many reports, despite the diligent attention to many of the earlier-mentioned risk factors, almost two of three patients who have delivered preterm had no easily identified risk factor. In addition, many patients delivered preterm report no perception of uterine activity (Garbaciak JA, Desch C, unpublished data). Other investigators have concluded that because most of the potentially preventable births occur in groups that present with marked cervical dilatation, it may be difficult to lower significantly the preterm birth rate below the current levels. Despite the sometimes dismal outlook regarding the prevention of preterm labor and delivery, the multiple investigators that have reported certain successes in their study populations should give us hope and encourage us to apply those techniques that appear appropriate and effective in our individual populations and patients. We can see and measure successful outcomes only if we are willing to look and aggressively to attempt to decrease untoward perinatal events.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1617876 TI - Predicting prematurity: the mammary stimulation test. AB - The MST appears to have theoretical rationale, predictive utility, simplicity, safety, and low cost that suggests that its routine use in prematurity prevention may ultimately save significant health care dollars. Presently, the MST should be used as an adjunct to prenatal care until further and more definitive investigation has been conducted; however, it seems promising that the MST will provide some reassurance in patients with negative tests and signify patients that are at significant risk for premature delivery (positive MST). It is hoped that further investigation will validate the MST's use in prematurity prevention in order to help decrease the incidence of preterm delivery. PMID- 1617877 TI - An aspirin a day to prevent prematurity. AB - Intrauterine fetal growth retardation and preeclampsia remain a substantial cause of preterm birth world wide. There is evidence to suggest that a functional imbalance between vascular prostacyclin and platelet-derived thromboxane A2 production plays a central role in the pathogenesis of these disorders. Low-dose aspirin appears to reverse the above functional balance resulting in increased prostacyclin to thromboxane ratio. The efficacy and safety of low-dose aspirin in preventing preeclampsia and fetal growth retardation were tested in several randomized and uncontrolled trials. The data in the literature suggest that low dose aspirin is effective in reducing preterm birth due to the above complications in selected high-risk pregnant women. PMID- 1617878 TI - Uterine surgical approaches to reduce prematurity. AB - Success rates of up to 80% can be expected after surgical treatment of abnormal uteri. A careful investigation should be conducted to verify that other causes of prematurity are not present prior to surgical intervention. PMID- 1617879 TI - Home uterine activity monitoring. AB - Despite tremendous improvements in maternal and neonatal care, preterm delivery remains the leading cause of infant mortality. Widespread use of tocolytics and aggressive preterm labor management have had little effect on reducing the overall neonatal mortality. To improve the success of tocolysis and preterm labor management, it is critical that preterm labor be diagnosed prior to significant cervical change. At present, a combination of several components is indicated for successful preterm birth prevention programs. These should include periodic risk assessment, patient education, cervical assessment, daily contact by highly skilled perinatal nurses, daily home uterine activity monitoring, and aggressive patient management. Studies support that this approach results in early detection of preterm labor, subsequently more effective tocolytic therapy and prevention of preterm birth. PMID- 1617880 TI - Multiple gestation: the role of multifetal pregnancy reduction and selective termination. AB - With the increased use of fertility agents and the transfer of multiple embryos, multifetal gestations have increased in number. As the number of fetuses increases, the probability of premature birth and delivery does. The role of multifetal pregnancy reduction and selective termination is reviewed. PMID- 1617881 TI - Polyhydramnios: does reducing the amniotic fluid volume decrease the incidence of prematurity? AB - Polyhydramnios is an uncommon cause of premature labor and delivery. After sonographic evaluation has confirmed the polyhydramnios and a determination is made of the potential etiologies, indomethacin appears to be an effective agent in reducing the amniotic fluid volume and in preventing prematurity. PMID- 1617882 TI - Premature rupture of the membranes: management controversies. AB - Preterm premature rupture of the membranes continues to be a leading cause of perinatal morbidity and mortality in the United States. In the absence of amnionitis or fetal compromise, expectant management is a reasonable alternative to permit fetal weight gain and to allow for fetal lung maturation. When embarking on an expectant management course, a variety of clinical approaches are available to the practicing clinician. PMID- 1617883 TI - Amnioinfusion with preterm, premature rupture of membranes. AB - Excluding labor, the greatest risks to the fetus from preterm PROM are umbilical cord accidents and infection. Heretofore, the clinical options for the PROM patient have been limited. With the advent and refinement of amnioinfusion, the utility of expectant management may be greatly increased. Through the use of amnioinfusion or its permutations, a number of diagnostic and therapeutic procedures previously unavailable to the PROM patient may become routine, including amniotic fluid volume expansion and direct in utero prophylaxis/treatment of amnionitis. PMID- 1617884 TI - The low birth weight infant: is there a preferred route of delivery? AB - In the management of the preterm pregnancy, cesarean delivery cannot be supported in the delivery of the preterm (less than 1500 g) cephalic-presenting fetus. Although cesarean may be of benefit in the management of the preterm breech fetus (less than 1500 g), there is yet no perspective randomized clinical trial to support its use. PMID- 1617885 TI - Placenta previa. AB - Placenta previa occurs in approximately one in 200 pregnancies. The cause is unknown, but endometrial damage due to prior pregnancy, cesarean section, and other factors predispose to it. Diagnosis is usually made by transabdominal ultrasonography. False-positive diagnoses are common in the second trimester and the term "potential placenta previa" has been proposed to describe this situation. Bleeding with placenta previa is usually associated with uterine contractions, thus the introduction of tocolysis. Placenta accreta is common in the patient with one or more previous cesarean sections and placenta previa in the current pregnancy. Management of placenta previa is expectant and involves avoidance of digital vaginal examination, delay of delivery until 36 weeks' gestation and/or documented fetal lung maturity, transfusion support to maintain maternal hematocrit greater than or equal to 30%, serial ultrasonography, antepartum fetal heart rate monitoring, glucocorticoids, tocolytic therapy, and elective delivery by cesarean section. Maternal mortality is rare with placenta previa. Perinatal mortality is currently 4% to 8% primarily related to complications of prematurity. PMID- 1617886 TI - Antepartum fetal surveillance in the preterm fetus. AB - Over the past two decades, obstetric and neonatal health care has shifted its attention to the preterm pregnancy. Due to the immaturity of the fetal autonomic nervous system, the usual diagnostic criteria for intervention in the preterm fetus are not available. Alternative methods such as the biophysical profile and Doppler offer the clinician a reasonable alternative in identifying potential fetal compromise. PMID- 1617887 TI - Obstetric critical care issues in prematurity. AB - Typically, obstetric critical care issues focus on the management of the patients whose pregnancies are complicated by severe preeclampsia and oliguria. Here, the focus is on the expectant management of the preterm pregnancy complicated by severe preeclampsia, HELLP syndrome, or eclampsia. Then, the emphasis shifts to tocolytic and severe preeclampsia-related pulmonary edema and its clinical management. PMID- 1617888 TI - Neonatal management of the very low birth weight infant: the use of surfactant. AB - The use of surfactant in the low birth weight infant with respiratory distress syndrome has undergone multicenter randomized clinical trials. This article addresses the properties of surfactant, the clinical aspects of surfactant replacement therapy and the implications for future research. PMID- 1617889 TI - Ethical issues in obstetric cases involving prematurity. AB - This article explores the ethical issues confronted when the process of childbirth is threatened by premature labor and delivery. In this article, obstetric ethics are distinguished within the larger study of "ethics," frameworks for decision making are critiqued, and factors that frequently influence the formation of ethical judgments are commented on. PMID- 1617890 TI - Effect of rheumatoid arthritis upon other members of the family. PMID- 1617891 TI - The role of pregnancy in the course and aetiology of rheumatoid arthritis. AB - The aetiology of rheumatoid arthritis (RA) is unknown, although being female is generally recognized as the most important independent risk factor, the disease being 2 to 3 times more frequent in females than in males. The dramatic effect of pregnancy in rheumatoid arthritis has been documented for over 50 years. This review examines the evidence and possible mechanisms by which pregnancy modifies the disease process and may alter predisposition to the development of RA in later life. PMID- 1617892 TI - Pulmonary hypertension in MCTD: report of two cases with anticardiolipin antibody. AB - We report on 2 patients with well-documented mixed connective tissue disease (MCTD) accompanied by severe pulmonary hypertension (PH) due to thrombosis or thromboembolism. In a previous report we indicated (1) that patients with MCTD complicated by PH have a significantly worse prognosis than patients with other connective tissue disease (CTD) complicated by PH. Both our patients had anticardiolipin antibody (a-CL) in the initial stages of the disease. We also studied the relationship of a-CL to PH in patients with other CTD. Patients of either MCTD or SLE with high levels of a-CL had significantly higher values of mean pulmonary arterial pressure than patients without a-CL. Several factors were suggested for the pathogenesis of PH such as vasospasm, arteritis, platelet dysfunction, and thrombosis or thromboembolism. The presence of a-CL may be one of important factors in development of PH among patients with MCTD with recurrent pulmonary thrombosis or thromboembolism. PMID- 1617893 TI - Serum levels of interleukin-1b, tumour necrosis factor-a and interleukin-2 in rheumatoid arthritis. Correlation with disease activity. AB - Cytokines are potent immunoregulatory factors and may be directly involved in the disordered immunoregulation found in chronic rheumatic diseases. Interleukin-1b (IL-1b), Interleukin-2 (IL-2) and Tumour Necrosis Factor-a (TNF-a) have been implicated in the pathogenesis of rheumatoid arthritis (RA) as mediators of chronic inflammation. Serum levels of IL-1b and TNF-a measured by radioimmunoassay were significantly higher in patients with RA than in healthy controls of similar sex and age while serum levels of IL-2 were significantly lower in the same patients. Further IL-1b and TNF-a were significantly elevated in RA patients with active disease and IL-2 was significantly reduced when compared with patients with low active disease. Serum IL-1b and TNF-a appear to correlate with systemic inflammation, and systemic features of RA may result from dissemination of cytokines produced in the synovium. The role of IL-2 in RA remains controversial. Reduced levels of IL-2 may be an expression of a deficiency of T-cells to produce IL-2 in the active phases of RA or may be due to a possible absorption of IL-2 by lymphocyte receptors. PMID- 1617894 TI - Serum anti-tropo:anti-alpha-elastin antibody ratio assessing elastin turnover in scleroderma. AB - Serum antibodies to native (tropo) and denatured (alpha) elastins appear to correlate with the production and breakdown respectively of elastic tissue. Elastin may be degraded as a part of autoimmune diseases. This possibility was tested by measuring IgG antibodies to tropo- and alpha-elastins by ELISA in the sera of 111 patients with a variety of connective tissue diseases compared with 18 healthy individuals. Anti-alpha-elastin antibodies were significantly higher in sera from 18 scleroderma patients than from healthy controls (p less than 0.008). Conversely, anti-tropoelastin antibody levels for scleroderma patients (p less than 0.03) and for patients with a variety of other connective tissue diseases (p less than 0.02) were lower than in healthy controls. Low antibody levels to native elastin and high levels of antibodies to denatured elastin suggest a low synthesis: degradation ratio for elastin in scleroderma. Scleroderma may be a unique model for elastin turnover because of its heretofore unrecognized accelerated elastolysis. PMID- 1617895 TI - Plasminogen activator inhibitor and von Willebrand factor in polymyalgia rheumatica. AB - Endothelial cell products, plasminogen activator inhibitor (PAI) and von Willebrand factor (vWF), were assayed in 25 patients with newly-diagnosed and untreated polymyalgia rheumatica (PMR), before and after three and 12 months of corticosteroid treatment. The mean values of PAI and vWF, and also the levels of acute phase reactants (erythrocyte sedimentation rate, fibrinogen, haptoglobin, orosomucoid, C-reactive protein) and platelet counts, were elevated in the active untreated disease. In contrast to the acute phase proteins, both PAI and vWF remained increased after three and 12 months of glucocorticoid treatment. This suggested an active vasculitis, despite a clinically-inactive disease. Particularly high levels of vWF both before and after glucocorticoid therapy were found in two patients who subsequently developed vascular complications during the follow-up period. PMID- 1617896 TI - Management of proteinuria secondary to penicillamine therapy in rheumatoid arthritis. AB - To determine if a policy of continuing penicillamine therapy in successfully treated patients with rheumatoid arthritis in the presence of persistent proteinuria, was associated or not with resolution of this adverse effect, a computer record of patients receiving penicillamine for rheumatoid arthritis was searched for patients with persistent proteinuria and the case notes of these patients reviewed. Eleven patients with persistent proteinuria were identified, eight of whom did not have nephrotic syndrome and were continued on penicillamine with close monitoring. In 5 patients proteinuria resolved after 16-21 months; 3 developed peripheral oedema (2) or worsening of pre-existing hypertension and proteinuria (1). In one of these the proteinuria subsequently resolved and one died of unknown cause. Of the 3 initially nephrotic patients, two had resolved at the time of the study. Persistent proteinuria in penicillamine-treated patients with rheumatoid arthritis resolves with continued therapy in the absence of nephrotic syndrome but vigilance is required for the development of any complications. PMID- 1617897 TI - Psychosocial factors and self-help in ankylosing spondylitis patients. AB - The purpose of this research was to investigate psychological factors associated with ankylosing spondylitis (AS), focusing on possible differences between members and nonmembers of self-help groups for people with this form of chronic disease. Analysis of health locus of control beliefs along 3 dimensions: internality, powerful others and chance, showed that members of National Ankylosing Spondylitis Society (NASS) self-help groups placed significantly less reliance on "powerful others" for control of health than did nonmembers. This pattern of beliefs may be related to the nature of AS, which is incurable, progressive, unpredictable and difficult to diagnose. It may therefore appear to the patient that health care professionals have little to offer them. People who join a self-help group may also feel less reliant on medical personnel to control their health. Group members also differed from nonmembers in terms of belief in the value of exercise for AS, frequency of exercise, tendency to seek information about the disorder and perceived social support. A combination of psychosocial and medical variables discriminated between members and nonmembers at a rate of 71.9% accuracy. Results indicate that NASS self-help group members appear to comply more with exercise treatment and also receive a valuable source of social support from fellow members. This investigation demonstrates the utility of including psychosocial variables in the study of chronic disease. PMID- 1617898 TI - Renal tubular acidosis in primary Sjogren's syndrome. AB - Renal tubular acidosis (RTA) is a frequent extraglandular manifestation of Sjogren's syndrome; however, no distinction on the incidence of this renal tubular defect between primary and secondary Sjogren's syndrome has been reported. This study was undertaken in order to define the frequency of RTA and the possible pathogenetic mechanisms in a group of 21 randomly selected primary Sjogren's syndrome patients. RTA was found in 7 (33%) patients. The incomplete type of the disorder was the most frequent. It seems that the etiology of RTA is multifactorial. Renal excretion of monoclonal proteins and the immunologically induced interstitial inflammation are the main possible factors of this renal tubular defect. PMID- 1617899 TI - Osteophytosis of the knee: association with changes in weight-bearing exercise. AB - Osteoarthritis has been held to result from wear and tear. We addressed this hypothesis by analysis of anteroposterior radiographs of the knees of 51 subjects with mean age of 60 years who regularly practiced weight-bearing exercise. Radiographs were assessed for longitudinal changes in spur formation over a two year period. The results showed a negative association between changes in weight bearing exercise and changes in the rate of spur development in both males and females. The findings suggest that increasing repetitive impulse loading in the form of regular painless weight-bearing activity does not promote osteophytosis (or perhaps degenerative disease) in knee joints. PMID- 1617900 TI - HLA B27 and clinical features in Reiter's syndrome. AB - HLA B27 and other clinical findings were investigated in 18 Turkish patients with Reiter's syndrome (mean age 35.8 +/- 8.09). Male/female ratio was 2/1. All 18 patients were seronegative, 12 (66.6%) presenting with an asymmetrical oligoarticular arthritis. Radiological sacroiliitis and enthesopathy was found in 9 (50%) and 7 (45.6%) patients respectively. HLA B27 was present in 11 (61.1%) patients. PMID- 1617901 TI - Mud pack therapy in rheumatoid arthritis. AB - Twenty-eight patients with classical or definite rheumatoid arthritis were randomly divided into two groups of fourteen patients each. All patients were treated once a day with mud packs derived from the Dead Sea heated to 40 degrees C and applied over the four extremities, neck and back for 20 minutes. Group 1 was treated with the true mud packs and Group 2 with washed out and less concentrated mud packs. The study was double blind and of two weeks duration. All patients were evaluated by one rheumatologist both before treatment and two weeks later at the end of the treatment period. Follow-up evaluations were made one and three months after conclusion of the treatment. The clinical indices evaluated included duration of morning stiffness, hand-grip strength, activities of daily living, patient's own assessment of disease activity, number of active joints and the Ritchie index. A statistically significant improvement (p less than 0.01 or p less than 0.05) was observed in Group 1 only in most of the clinical indices, lasting between 1 to 3 months. PMID- 1617902 TI - Prevalence of anti-endothelial cell antibodies in patients with autoimmune diseases. AB - The prevalence of anti-endothelial cell antibodies (AECA) of IgA, IgG and IgM classes was studied by means of enzyme-linked immunosorbent assays (ELISA) in 466 patients with autoimmune/inflammatory disorders. The reference limits in the ELISAs for the AECA were determined from a random population sample of 249 subjects. The frequency of AECA was highest in patients with SLE (n = 42), 14.6% mainly of IgG class, and the presence of AECA correlated with disease activity in these patients. In the RA patient group (n = 200), 9.5% had AECA, mostly of IgA type. We found no association between the presence of AECA and extra-articular manifestations of RA or survival rate. In patients with undefined connective tissue disease (n = 57), ankylosing spondylitis (n = 109), and psoriatic arthritis (n = 58), the frequency of AECA corresponded to that of the random population sample. In a cohort of samples sent to the laboratory for determination of anti-nuclear antibodies (ANA) there was a correlation between the presence of ANA and AECA. Our findings indicate that RA patients are characterized by IgA class AECA, whereas SLE patients have IgG class AECA also correlating to disease activity. PMID- 1617903 TI - HLA and Behcet's disease in northern Spain: their lack of correlation with arthritis pattern. AB - We have studied the characteristics of arthritis present in 32 patients with Behcet's disease (BD), and how this arthritis is related to the HLA markers class I. 84% of the patients presented arthritis, the most common being mono-arthritis as the initial presentation, and oligoarthritis in subsequent episodes. In 63% of the cases, the development was in episodes of acute/subacute arthritis. We found statistically significant association between antigens B-5 and B-51, and the group with BD, with a relative risk of 3.89 and 4.71 respectively. The attempt to relate markers B-5, B-51 and B-27 to the presence of arthritis as well as to its manifestation and further development was not conclusive. PMID- 1617904 TI - HLA typing and seropositivity in Finnish and in Polish patients with rheumatoid arthritis and amyloidosis. AB - We determined HLA-A, -B, -C and -DR antigens in 83 patients with rheumatoid arthritis (RA) and reactive secondary amyloidosis (RSA), 60 in Finland and 23 in Poland, and compared the results with control RA patients and blood donors. There were no significant differences in the frequencies of HLA between the RA patients with and those without RSA in either Finland or Poland, and no significant differences between the Finnish and Polish patients with RSA. All the RSA patients from Finland and 70% of the RSA patients from Poland were seropositive. In the development of RSA, the prolonged period of inflammatory stimuli may play a more important role than genetic factors. PMID- 1617905 TI - Cerebral involvement in adult onset Still's disease. AB - Still's disease was diagnosed in a 40-year-old patient as a cause of psycho organic syndrome with complete disorientation and stupor, sensory and motor aphasia. There were no signs of a tumour, cerebrovascular accident, bacterial or viral infection. The patient recovered quickly from the cerebral disturbances under treatment with corticosteroids. Similar symptoms in adult patients with Still's disease are seldom found in the literature. PMID- 1617906 TI - Polyarthritis associated with hydatid disease (echinococcosis) of the liver. AB - A 36-year-old male developed asymmetric polyarthritis during the course of hydatid disease of the liver. Excision of the hydatid cyst was accompanied by full remission of the arthritis without recurrence during the 7-year follow-up period. This sequence of clinical events suggests an eventual cause and effect relationship. A "reactive" immune mechanism, triggered by a parasite located at a distant site, appears to be responsible for this type of arthritis. PMID- 1617907 TI - Nonsteroidal anti-inflammatory drugs and gallstone formation. PMID- 1617908 TI - FDA announces four initiatives for drug approval system. PMID- 1617909 TI - Value of transdermal fentanyl. PMID- 1617910 TI - Oxaprozin: a once-daily nonsteroidal anti-inflammatory drug. AB - The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of oxaprozin are reviewed. Oxaprozin, a nonsteroidal anti-inflammatory drug (NSAID) under consideration for approval by the Food and Drug Administration, is characterized as a propionic acid. By inhibiting cyclo oxygenase, oxaprozin decreases the formation of prostaglandin (PG) precursors from arachidonic acid, resulting in decreased PG biosynthesis and reduced pain and inflammatory responses. Oxaprozin is well absorbed after oral administration, and peak plasma concentration is reached in three to six hours. Oxaprozin is primarily eliminated by urinary excretion of the unchanged drug. It has a long elimination half-life and persists in synovial fluid. In clinical studies, oxaprozin was equally or more effective than aspirin and as effective as naproxen in the treatment of rheumatoid arthritis. For treatment of osteoarthritis, oxaprozin was as effective as naproxen and more effective than aspirin or piroxicam. Studies have also shown oxaprozin to be effective therapy for juvenile rheumatoid arthritis and ankylosing spondylitis. Oxaprozin, like other NSAIDs, can cause gastrointestinal adverse effects. Other possible adverse effects include allergic reactions, analgesic nephropathy, hepatotoxicity, and increased bleeding times. For adults, the anticipated daily dosage is 600-1200 mg given as a single dose for rheumatoid arthritis, osteoarthritis, and analgesia. In children, oxaprozin 10-20 mg/kg/day has been used to treat juvenile rheumatoid arthritis. Oxaprozin is as effective as other NSAIDs and offers once-daily dosing; however, it does not offer any therapeutic advantage over other currently available NSAIDs. PMID- 1617911 TI - Ticlopidine: a new platelet aggregation inhibitor. AB - The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of ticlopidine are reviewed. Ticlopidine appears to inhibit platelet aggregation induced by adenosine diphosphate. Ticlopidine hydrochloride is rapidly absorbed after oral administration, and maximum antiplatelet effects occur one to three hours after the dose. In multicenter, randomized, double-blind trials, ticlopidine was more effective than aspirin or placebo in preventing stroke, myocardial infarction, or death caused by vascular events. Ticlopidine was more effective than aspirin in preventing recurrent transient ischemic attacks after six months of therapy. Ticlopidine has also been used to prevent occlusion and improve patency of aortocoronary bypass grafts, to prevent ischemic ulcers in patients with chronic arterial occlusive disease, and to slow the progression of diabetic microangiopathy. The most serious adverse effect, neutropenia, occurred in about 1% of patients. The most frequently reported adverse effects are diarrhea, nausea, vomiting, and abdominal cramps. Ticlopidine is indicated for reducing the risk of thrombotic stroke in patients who have experienced a minor stroke, transient ischemic attack, or completed thrombotic stroke. The recommended dosage is 500 mg/day in two divided doses taken with food. Ticlopidine is an alternative agent for the primary and secondary prevention of stroke. Because of the risk of neutropenia and agranulocytosis and the high cost of therapy, ticlopidine should be reserved for patients who are intolerant of or lack benefit from aspirin. PMID- 1617912 TI - Long-term dobutamine therapy for refractory congestive heart failure. AB - The proposed benefit of long-term dobutamine therapy is explained, relevant clinical trials are described, and recommendations for this treatment are discussed. Dobutamine increases cardiac contractility and causes vasodilation with little change in heart rate. It is routinely administered for short periods to relieve exacerbations of congestive heart failure (CHF) in hospitalized patients. Sustained effects have been seen with dobutamine infusions, although the known properties of the drug do not explain these effects. Long-term dobutamine therapy can lessen the symptoms of CHF and improve exercise tolerance and cardiac function. Nine published reports showed consistent improvement in 77 patients treated with multiple infusions of dobutamine. At Ohio State University, long-term dobutamine therapy (typically 5.0-7.5 micrograms/kg/min infused continuously) is used in patients with refractory CHF and those awaiting heart transplantation. Because the therapy does not prolong survival in most patients, specific endpoints of therapy should be determined for each patient. Because it may cause sudden death, patients receiving this therapy must be carefully monitored. Long-term use of dobutamine infusion lessens the symptoms of CHF but does not prolong survival. PMID- 1617913 TI - Influence of sucralfate on the detection of occult blood in simulated gastric fluid by two screening tests. AB - The influence of sucralfate on the detection of occult blood in simulated gastric fluid by two screening tests was investigated. Two simulated gastric solutions (pH 1.2 and 4.1) containing sucralfate 2.5 or 10 mg/mL were spiked with fresh whole blood (hemoglobin concentration, 15.7 g/dL) to achieve a blood concentration of 1 or 5 microL/mL. Fifty-microliter samples were applied to separate Hemoccult and Gastroccult test slides, which were read by a blinded evaluator at 60, 120, and 180 seconds after the addition of developer. Any trace of blue in the test area was considered a positive result. Sucralfate-free simulated gastric fluid spiked with blood served as a positive control, and fluid with or without sucralfate and containing no blood served as a negative control. No false-positive or false-negative results were obtained with Gastroccult. Hemoccult yielded false-positive results in 3 of 20 determinations at 60 seconds for solution containing sucralfate 10 mg/mL (pH 1.2) and 13 of 20 determinations at 60 seconds for solution containing sucralfate 2.5 mg/mL (pH 1.2). All the results with Hemoccult were positive when the slides were read at 120 and 180 seconds. Also, all the results for the negative controls were positive at 120 seconds. Hemoccult did not produce any false-negative results. False-positive results occurred when Hemoccult was used to test simulated gastric fluid that had a low pH (1.2) and contained sucralfate. Gastroccult did not yield false-positive results. PMID- 1617914 TI - Safety and tolerability of an intravenous immune globulin at various concentrations in 5% dextrose injection or sterile water for injection. PMID- 1617915 TI - Warfarin-induced intramural hematoma of the small intestine. AB - A case of warfarin-induced intramural hematoma and hemorrhagic infarction of the small intestine is described, and the literature on this adverse effect is reviewed. A 32-year-old white woman who had been receiving warfarin and carbamazepine came to a clinic complaining of lower back and stomach pain. She had a history of iliofemoral deep venous thromboses and seizures. A pelvic sonogram showed a large quantity of fluid present. Her prothrombin time (PT) was 29.2 sec. Her hemoglobin concentration and hematocrit were within the normal ranges. The patient was admitted to the hospital when her back pain increased and she vomited. The warfarin was discontinued. On day 5 the patient was still having abdominal pain and nausea. Her hemoglobin concentration and hematocrit had fallen to 6.6 g/dL and 20%, although her PT had decreased to 12.5 sec. On the same day, the patient underwent an exploratory laparotomy, and an indurated and ischemic area of jejunum was found and resected. The pathology report indicated the presence of hemorrhage and infarction consistent with an anticoagulant-related disorder. About 100 cases of intramural hematoma of the small intestine induced by anticoagulant therapy have been reported. Most patients are white males about 60 years of age. The sites most frequently involved are the duodenum and proximal jejunum. Symptoms include constipation, nausea, vomiting, and abdominal pain. Laboratory test and radiological findings are fairly nonspecific, but when found together in a patient receiving an anticoagulant, the diagnosis can be made with some confidence. Management may be complicated by the bleeding disorder, the intestinal obstruction if present, and the original indication for warfarin therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617916 TI - Sucralfate-associated aluminum toxicity in a patient with renal failure: treatment with deferoxamine. PMID- 1617917 TI - Domain-specific reasoning: social contracts, cheating, and perspective change. AB - What counts as human rationality: reasoning processes that embody content independent formal theories, such as propositional logic, or reasoning processes that are well designed for solving important adaptive problems? Most theories of human reasoning have been based on content-independent formal rationality, whereas adaptive reasoning, ecological or evolutionary, has been little explored. We elaborate and test an evolutionary approach. Cosmides' (1989) social contract theory, using the Wason selection task. In the first part, we disentangle the theoretical concept of a "social contract" from that of a "cheater-detection algorithm". We demonstrate that the fact that a rule is perceived as a social contract--or a conditional permission or obligation, as Cheng and Holyoak (1985) proposed--is not sufficient to elicit Cosmides' striking results, which we replicated. The crucial issue is not semantic (the meaning of the rule), but pragmatic: whether a person is cued into the perspective of a party who can be cheated. In the second part, we distinguish between social contracts with bilateral and unilateral cheating options. Perspective change in contracts with bilateral cheating options turns P & not-Q responses into not-P & Q responses. The results strongly support social contract theory, contradict availability theory, and cannot be accounted for by pragmatic reasoning schema theory, which lacks the pragmatic concepts of perspectives and cheating detection. PMID- 1617918 TI - Modal reasoning, models, and Manktelow and Over. AB - Manktelow and Over (1991) argue that their studies of Wason's selection task favor explanations of deontic reasoning based on mental models, but that such theories need to incorporate utilities. This theoretical note proposes a simpler explanation of the phenomena: subjects in the selection task consider only those cards that are explicitly represented in their models of the conditional, and so insight into the task depends on constructing fully explicit models. Such models for modal conditionals of the form, If p occurs then q may occur are: [formula: see text] Each line denotes a separate model, and the models represent either what is possible, or, in the deontic interpretation, what is permissible. A deontic rule is accordingly violated by the contingency: [symbol: see text] p and q, for example the rule, "If you spend more than 100 pounds, then you may take a free gift" is violated by taking the free gift (q) but not spending more than 100 pounds ([symbol: see text] p). If the rule is interpreted as a bi-conditional, then the second of the models, p and [symbol: see text] q, is also now a violation, for example spending more than 100 pounds (p) but not getting the free gift ([symbol: see text] q). Manktelow and Over's instructions lead subjects to focus on one or other of the two sorts of violations of the rule. There is accordingly no need to introduce utilities into models in order to explain the phenomena. PMID- 1617919 TI - Utility and deontic reasoning: some comments on Johnson-Laird and Byrne. PMID- 1617920 TI - The early development of numerical reasoning. AB - Children of age 1-4 years were found capable of engaging in numerical reasoning. Children were presented with a task in which they placed a set of objects one by one into an opaque container. An experimenter then visibly performed either an addition, a subtraction, or no transformation on the screened set. Children were then instructed to remove all objects from the container. Across two experiments, children searched for and removed the correct number of objects when set numerosity was small. Knowledge of numerical identity and knowledge of the effects of addition and subtraction transformations on numerosity were present even in children who had not yet begun to count verbally. These findings provide evidence that the emergence of numerical reasoning does not depend upon the prior development of a verbal counting ability or upon cultural experience with numbers. PMID- 1617921 TI - Factors affecting nonadherence with antibiotics. AB - Nonadherence with antibiotic therapy has profound implications both for patient health and the health care system that bears the financial costs incurred. Significant levels of nonadherence with antibiotic prescriptions have been demonstrated. Of the many proposed variables involved, those that are potentially modifiable relate to aspects of the doctor-patient interaction and drug regimen. Despite the potential for intervention with these variables, there have been very few methodologically sound studies examining their effect on adherence with either medications generally or antibiotics specifically. Only two studies were located that had tested the effectiveness of reduced complexity of antibiotic dosage schedules. The results suggest that the less complex the schedule, the greater is the adherence. Both practitioners and patients must be encouraged to use and accept simpler dosage schedules, preferably once-daily schedules wherever possible. The paucity of well-controlled studies to date highlights the need for further research evaluating intervention strategies that utilize variations in dosage schedule and elements of the doctor-patient interaction to improve adherence with antibiotic medications. PMID- 1617922 TI - Clinical evaluation of roxithromycin 300 mg once daily as an alternative to 150 mg twice daily. AB - A multicenter, double-blind, randomized, two-arm study was conducted to compare two dosage regimens of roxithromycin--150 mg b.i.d. and 300 mg once daily--in 1588 patients with infectious disease, 1573 of whom were evaluable for safety and 1391 for efficacy. There were no significant differences in demographic or disease characteristics at presentation. Treatment duration averaged 10 days in both groups. Clinical response rates (% satisfactory response) were similar in both arms (b.i.d. versus once daily, respectively): upper respiratory tract, 95.3 and 95.0; lower respiratory tract, 93.1 and 93.6; and skin and soft tissue, 93.1 and 93.0. Bacteriologic response was also similar. The overall incidences of adverse events were 8.5% for daily dosing and 7.2% for b.i.d. dosing, but there was a slightly greater frequency of gastrointestinal events (p less than 0.03) was observed with the once-daily regimen. Thus roxithromycin 300 mg once daily can be recommended as an effective and well-tolerated alternative to the conventional b.i.d. regimen. PMID- 1617923 TI - Roxithromycin versus doxycycline in the treatment of acute exacerbations of chronic bronchitis. AB - The efficacy and safety of roxithromycin (300 mg once daily) and doxycycline (200 mg once daily) in the treatment of acute exacerbations of chronic bronchitis in general practice were compared in a multicenter, double-blind, double-dummy trial. The data presented here are the results of an interim analysis of 76 patients. A satisfactory clinical response was obtained in 81% of patients treated with roxithromycin and 80% of those treated with doxycycline. Among patients receiving roxithromycin, 12.2% volunteered adverse events, compared with 33% of those receiving doxycycline; the test treatments were considered possibly or probably responsible for the adverse events in 9.8% and 21.2% of cases, respectively. Though patient numbers are too small for statistically significant differences to be detected, we conclude that the results to date suggest that roxithromycin and doxycycline are equivalent in terms of efficacy, but that roxithromycin is better tolerated. PMID- 1617924 TI - A randomized, comparative study of the efficacy and tolerance of roxithromycin and doxycycline in the treatment of women with positive endocervical cultures for Chlamydia trachomatis and Mycoplasma spp. in an in vitro fertilization program. AB - A total of 45 patients wishing to enter an in vitro fertilization program had positive endocervical cultures for Chlamydia trachomatis, 86 had positive cultures for Ureaplasma urealyticum, and 11 had positive cultures for Mycoplasma hominis. These patients and their consorts were randomly allocated to treatment with either roxithromycin or doxycycline. Both antibiotics were completely effective against C. trachomatis. In patients with U. urealyticum infection, roxithromycin was successful in 73% and doxycycline in 87% of cases. Mycoplasma hominis was eradicated in 100% of cases by doxycycline and in 85% of cases by roxithromycin. Doxycycline caused significantly more side effects than did roxithromycin. PMID- 1617925 TI - Multicenter double-blind study of the efficacy and tolerance of roxithromycin versus erythromycin ethylsuccinate in acute orodental infection in adults. Odontogenic Infections Study Group. AB - A total of 194 patients with orodental infection were randomized either to roxithromycin 150 mg twice daily plus placebo or to erythromycin 1 g twice daily plus placebo for a mean duration of 8 days. The infections consisted of cellulitis, pericoronitis, and adenopathy, or any two in combination. In the 176 cases in which efficacy was evaluable, outcome was satisfactory in 94% and 91% of cases treated with roxithromycin and erythromycin, respectively (p = 0.45). Patients were evenly distributed with respect to demographic characteristics, diagnosis, and concomitant treatment. Surgery was performed in 63%, primarily for abscess formation in cellulitis (p less than 0.001); 18% of patients with an abscess did not undergo surgery. The success rate was identical irrespective of whether surgery was performed, including in those with an abscess. Tolerance was evaluated in 1986 patients. Unwanted effects, elicited by direct questioning, were reported in approximately 20% of cases per group (19% for roxithromycin and 21% for erythromycin). They consisted of mild gastrointestinal upsets which caused treatment to be withdrawn in eight cases (four per group). Thus, roxithromycin and erythromycin twice daily for orodental infection are similar in both efficacy and tolerance. PMID- 1617926 TI - In vitro activity of roxithromycin against Moraxella catarrhalis. AB - The in vitro activity of roxithromycin was compared with that of the other antimicrobial agents (erythromycin, tetracycline, ampicillin, and cotrimoxazole) against 188 distinct clinical isolates of Moraxella catarrhalis. Of these, 106 strains (66%) produced beta-lactamase. The MIC90 of roxithromycin was 0.25 micrograms/ml compared with values of 0.5, 1, greater than 8, greater than 8:0.4 micrograms/ml for erythromycin, tetracycline, ampicillin, and sulfamethoxazole trimethoprim, respectively. These results, allied with its improved pharmacokinetic properties, suggest that roxithromycin should be an effective treatment in children and adults for upper and lower respiratory tract infections caused by M. catarrhalis. PMID- 1617927 TI - The effect of roxithromycin on the virulence of gram-positive cocci. AB - Antibiotics whose recognized mode of action comprises inhibition of bacterial protein biosynthesis are also recognized to modulate the expression of bacterial virulence factors when incorporated into culture media at sub-MIC levels. In this respect, one of the new macrolides, roxithromycin, has been examined for its effect on toxin/enzyme production by strains of Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. Biosynthesis of staphylococcal coagulase and DNase could be potentiated, whereas that of staphylococcal alpha-hemolysin, streptolysins O and S, and pneumolysin were unaltered. Expression of one structural virulence factor, pneumococcal polysaccharide, was repressed in the drug's presence, resulting in potentiation of phagocytic ingestion of the drug-exposed bacteria. The drug failed to have any effect on ingestion of Staph. aureus or Strep. pyogenes. These studies provide evidence that roxithromycin may exhibit "added value" as an antibiotic in its ability to potentiate the susceptibility of Strep. pneumoniae to host defenses such as phagocytosis. PMID- 1617928 TI - Penetration of roxithromycin into gingival tissue. AB - Roxithromycin is a new macrolide with an antibacterial spectrum similar to that of erythromycin. Absorption is rapid and complete, resulting in high serum levels and a long half-life. Tissue distribution is extensive and sustained, as shown by the high concentrations measured in the lung, prostate, ovaries, liver, kidney, and skin. In this study, we measured the penetration of roxithromycin into gingival tissue at steady state in 30 patients treated orally with 150 mg every 12 hr for 5 days. Tissue specimens were sampled at 2, 4, 6, 8, or 12 hr (n = 6 each time) after dose 10, and blood samples were taken simultaneously. Serum and tissue concentrations of roxithromycin were measured by high-performance liquid chromatography. The peak serum level, reached 4 hr after dosing, was 6.60 +/- 1.15 micrograms/ml. The peak tissue level was 4.63 +/- 1.84 micrograms/g and was reached after 8 hr. From 4 to 10 hr after dosing, tissue concentrations were greater than 2 micrograms/g, that is, higher than the MIC90 of roxithromycin against most oral pathogens. These data support the use of roxithromycin in the treatment of oral infections. PMID- 1617929 TI - An international clinical trial on the efficacy and safety of roxithromycin in 40,000 patients with acute community-acquired respiratory tract infections. AB - An ongoing eight-country study is being conducted in an unprecedented number of general practice patients with acute upper and lower respiratory tract infections to compare the efficacy and tolerance of roxithromycin 150 mg b.i.d. for 7-14 days with the data acquired in the prelaunch studies of these same parameters. The target population is 40,000 (to be achieved by the end of 1991) and we report the interim results from 32,405 patients, 18,020 with upper and 14,385 with lower respiratory tract infections. In acute pharyngitis/tonsillitis sinusitis, and otitis, clinical resolution or improvement has been achieved in 97%, 96%, and 96% of cases, respectively. The figures for bronchitis, exacerbation of chronic bronchitis, and pneumonia are 97%, 94%, and 95%. Side effects have been reported in only 4% of patients to date, 75% consisting of moderate gastrointestinal upsets. Of the patients, 1% withdrew from treatment because of side effects. These interim figures confirm the data from the prelaunch, controlled comparative trials and show roxithromycin to be an appropriate choice of first-line antibiotic therapy in the management of respiratory tract infections in general practice. PMID- 1617930 TI - Comparison of two oral antibiotics, roxithromycin and amoxicillin plus clavulanic acid, in lower respiratory tract infections. AB - In a randomized, multicenter, open-label study, 490 ambulatory adult patients with lower respiratory tract infection (LRTI) were randomized to roxithromycin (ROX) 150 mg b.i.d. orally (n = 244) or amoxicillin plus clavulanic acid (AMX + CA) as 500 mg AMX + 125 mg CA t.i.d orally (n = 24). Clinical results were analyzed in 477 patients with acute bronchitis (79%), chronic bronchitis (CB) (14%), and pneumonia (7%). There were significantly more patients with underlying disease (cardiovascular diseases, p = 0.045; and alcoholism, (p less than 0.001), and more patients over the age of 65 years (p = 0.045) in the ROX group. Overall clinical efficacy was similar in both groups: 88% (206:235) in the ROX group and 85% (205:242) in the AMX + CA group. Side effects were reported in 67 cases (28%) in the AMX + CA group and in 21 cases (9%) in the ROX group (p less than 0.0001), causing withdrawal in 21 and three cases, respectively (p less than 0.001). Thus, despite being administered to a significantly older and more ill group of patients with LRTI, roxithromycin was as effective as amoxicillin plus clavulanic acid and better tolerated. PMID- 1617931 TI - Roxithromycin versus amoxicillin-clavulanic acid in the treatment of respiratory tract infections. AB - A multicenter, double-blind, double-dummy trial was conducted in 96 general practice patients with upper and lower respiratory tract infection to compare the efficacy and tolerance of roxithromycin (150 mg b.i.d.) and amoxicillin clavulanic acid (500 mg/125 mg t.i.d.). Good clinical response was obtained in 96% and 95% of cases, respectively, but only 4% of patients receiving roxithromycin volunteered adverse events possibly or probably related to their test treatment, as opposed to 17% of those receiving amoxicillin-clavulanic acid. The results indicate that both drugs are equally effective in the treatment of respiratory tract infection, but that roxithromycin is better tolerated. PMID- 1617933 TI - Elevated urinary excretion of orotic acid in sheep caused by intraruminal infusion of sodium propionate. AB - 1. The effect of sodium propionate on urinary excretion of orotic acid was investigated. 2. Solutions containing sodium propionate or NaCl, 750 mM/day each, were continuously infused into the rumen for 10 days. 3. During NaCl infusion, an urinary orotic acid excretion of 290 +/- 80 micrograms/day was noted. The intraruminal infusion of sodium propionate raised the concentration of propionic acid in the rumen fluid from 14.0 +/- 0.9 to 26.9 +/- 1.9 mM. 4. During this experimental period the excretion of orotic acid via urine significantly increased to 492 +/- 30 micrograms/day. Parameters of nitrogen balance were not altered by propionate. 5. It is suggested that the site of propionate action in intact sheep is in the pyrimidine synthesis pathway. PMID- 1617932 TI - A randomized double-blind controlled trial of roxithromycin and cefaclor in the treatment of acute lower respiratory tract infections in general practice. AB - A multicenter, randomized, double-blind, single-dummy placebo-controlled study is being undertaken by the Research Unit of the Royal New Zealand College of General Practitioners to compare the efficacy and tolerance of 150 mg twice daily roxithromycin with 250 mg three times daily cefaclor in the treatment of 250 general practice patients with acute lower respiratory tract infections (LRTIs). Interim analysis of 200 patients reveals no statistically significant differences in the study parameters. Of the patients on roxithromycin and cefaclor, 83% and 67%, respectively, had a moderate or severe illness. Based on efficacy criteria, 96% of roxithromycin recipients and 99% of cefaclor recipients had a satisfactory or improved response. On an intention-to-treat basis, this was reduced to 95% for both treatment groups. Sputum grading and semiquantitative culturing was performed according to NCCLS standards. The most common isolates in order were Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Efficacy for bacteriologically evaluable cases was 87.5% for roxithromycin and 57% for cefaclor. Four patients on roxithromycin (3.9%) and 11 patients on cefaclor (11.3%) withdrew because of side effects probably or possibly related to the study treatment. The study is ongoing. PMID- 1617934 TI - The uptake and conversion of L-[U14C-] aspartate and L-[U14C-] alanine to 14CO2 by intact trophozoites of Giardia duodenalis. AB - 1. Intact trophozoites of Giardia duodenalis (clone P1C10) took up and metabolised L-[U14C-] aspartate to 14CO2 at rates of 10.27 +/- 0.76 and 27.6 +/- 2.07 ng hr-1 10(-6) cells in a simple maintenance medium (MM) and in a complex bile supplemented (BIS-33) medium respectively. 2. Intact trophozoite of G. duodenalis (clone P1C10) also took up and metabolised L-[U14C-] alanine to 14CO2 at rates of 20.6 +/- 1.1 and 91.4 +/- 17.5 ng hr-1 10(-6) cells in the simple (MM) and complex (BIS-33) medium respectively. 3. trophozoite sonicates contained significant levels of aspartate-2-oxoglutarate transaminase (AST; EC 2.6.1.1) and alanine-2-oxoglutarate transaminase (ALT; EC 2.6.2.2.). Specific activities (at 23 degrees C) were 95.1 +/- 11.3 and 87.3 +/- 9.8 nmol (min)-1 (mg protein)-1 respectively. 4. These observations suggest that Giardia has the capacity to utilise aspartate and alanine and possibly other amino acids as alternative sources of energy. 5. The extrusion or uptake of alanine by Giardia trophozoites may be dictated by the intracellular redox-status of the protozoan parasite or components in the external mileu. PMID- 1617935 TI - Distribution of 5'-nucleotidase in muscle of some marine fishes. AB - A preliminary examination for the purification and characterization of 5' nucleotidase of fish muscle was carried out and the following results were obtained. 1. The activities of 5'-nucleotidase in the muscles of marine vertebrates and invertebrates (total 11 species) were determined. The highest activity of 5'-nucleotidase was found in Blackrock fish Sebastes inermis, which was then used as a material for estimation of subcellular distribution and solubilization of the enzyme. 2. The 5'-nucleotidase of ordinary muscle of the fish Sebastes inermis was found in nuclear, microsomal and cytosolic fractions. About half of the total activity was found in the nuclear fraction, whereas the highest specific activity was observed in the microsomal fraction. 3. Complete solubilization of the enzyme was attained by using a high concentration of detergent such as Triton X-100, CHAPS, octylglucoside, octylthioglucoside and sodium deoxycholate, suggesting that the enzyme was tightly bound to the membrane. 4. Based on the results of solubility and stability tests, Triton X-100 seemed suitable for solubilizing 5'-nucleotidase from the membrane. 5. Microsomal 5'-nucleotidase was an Mg(2+)-activated enzyme, and no inactivation was observed up to 50 mM of Mg2+. PMID- 1617936 TI - Wide distribution of the skin type I collagen alpha 3 chain in bony fish. AB - 1. Skin Type I collagens were isolated from the five species of non-teleostean fish and examined with respect to their subunit chains. 2. In addition to alpha 1(I) and alpha 2(I) chains, a fish-specific chain, alpha 3(I), was previously found only in teleostean fish. The present study, however, has revealed the occurrence of alpha 3(I) in a chondrostean fish, white sturgeon. 3. The alpha 3(I) gene appears to have arisen from a duplication of the alpha 1(I) gene near the time of the adaptive radiation of bony fish. PMID- 1617937 TI - Study on fatty acid binding by proteins in yeast. Dissimilar results in Saccharomyces cerevisiae and Yarrowia lipolytica. AB - 1. The presence of soluble proteins with fatty acid binding activity was investigated in cell-free extracts from Saccharomyces cerevisiae and Yarrowia lipolytica cultures. 2. No significant fatty acid binding by proteins was detected in S. cerevisiae, even when grown on a fatty acid-rich medium, thus indicating that such proteins are not essential to fatty acid metabolism. 3. An inducible fatty acid binding protein (K0.5 = 3-4 microM) was found in Y. lipolytica which had grown on a minimal medium with palmitate as the sole source of carbon and energy. 4. The relative molecular mass of this protein was 100,000 as inferred from Sephacryl S-200 gel filtration. PMID- 1617938 TI - Purification and characterization of a latent form of multicatalytic proteinase from fish muscle. AB - 1. A latent form of multicatalytic proteinase (MCP) was purified to apparent homogeneity from white croaker muscle by DEAE-Sephacel, Mono-Q, Sephacryl S-300 and second Mono-Q chromatographies. 2. The enzyme preparation was electrophoretically and immunologically similar to MCP purified from the same source by a different method (Folco et al., 1988b, Archs Biochem. Biophys. 267, 599-605) but showed much lower chymotrypsin- and trypsin-like activities. 3. These activities responded to sodium dodecyl sulphate (SDS), urea and heat treatments in different ways: SDS stimulated both activities, urea stimulated the former and inhibited the latter and heating stimulated the former and did not affect the latter. 4. The stimulation of chymotrypsin-like activity by the three treatments was irreversible. 5. Exposure of MCP to SDS or urea in the absence of substrate rapidly inactivated it, whereas heat activation took place irrespective of the presence of substrate. 6. The stimulating effect of SDS on chymotrypsin like activity was lost in the presence of urea. 7. These results suggest that the enzyme may be activated by different mechanisms. PMID- 1617939 TI - Identification, comparison and partial characterization of glycoproteins in the hemolymph of Schistosoma mansoni (Trematoda)-susceptible and resistant Biomphalaria glabrata (Gastropoda). AB - 1. Glycoproteins in the plasma (cell-free hemolymph) of Schistosoma mansoni resistant and susceptible strains of Biomphalaria glabrata were identified, characterized and compared using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, electroblotting and a series of peroxidase-labeled lectins with different sugar specificities. 2. Schistosome-resistant snails possessed at least three glycoproteins (70, 116, 205 kDa) that were not present in plasma from susceptible snails. 3. Sporocysts (larval S. mansoni) preincubated in plasma from schistosome-resistant or susceptible B. glabrata adsorbed certain glycoproteins to their surface and some altered the binding of lectin probes to the parasite. 4. This study indicates that glycoproteins in the plasma of B. glabrata are associated with S. mansoni-susceptibility and resistance. PMID- 1617941 TI - A comparison of hepatic glucokinase gene expression in high- and low-activity strains of mice. AB - 1. Compared with the rat, mouse liver glucokinase activities show a different sensitivity to changes in insulin concentrations. When animals from a high glucokinase-high insulin level strain C3H/He are crossed with those from a low glucokinase-low insulin strain C58, individuals from recombinant inbred lines show non-parental phenotypes with high glucokinase activity but low insulin and vice versa. 2. Messenger RNA levels are greater in high-enzyme-activity mice strains than in low-activity animals, suggesting that differences in either transcription of the glucokinase gene or in mRNA stability occur between the two strains. 3. There is no evidence of a different number of glucokinase genes in the high- and low-activity strains. Differences in activity therefore suggest that dissimilarities in the regulation of the expression of these genes may well occur. PMID- 1617940 TI - Individual expression patterns of myotoxin isoforms in the venom of the snake Bothrops asper. AB - 1. In order to investigate the distribution of myotoxin isoforms in the snake Bothrops asper, venoms from individual specimens were analyzed by a cathodic electrophoretic system for basic proteins under native conditions. 2. The electrophoretic system resolved at least five bands with slight differences in mobility, corresponding to the fastest migrating proteins in the venom. The identity of the bands was confirmed by immunoblotting, using a rabbit anti myotoxin serum. 3. There were clear differences in the individual patterns of myotoxin isoform expression, both in specimens from the Atlantic and Pacific regions of Costa Rica. Some individuals possessed all five variants. 4. In agreement with previous reports, the venoms of ten newborn (less than 10 days of age) specimens completely lacked myotoxin bands, indicating an ontogenetic regulation in the expression of these toxins in B. asper. 5. One of the bands, corresponding to the lysine-49 phospholipase myotoxin II, was the only isoform present in all individuals studied, suggesting a possible selective pressure for the conservation of this type of protein in the venom of B. asper. PMID- 1617942 TI - Age-related changes of the branched-chain fatty acid concentration in rat skin surface lipid. AB - 1. Age-related change of the branched-chain fatty acid distribution in rat skin surface lipid was studied for 24 months. 2. The proportion of even carbon number iso-acid increased from infancy to month 5 and thereafter decreased with advancing age toward senescence. 3. Concentration of odd carbon number iso-acid depicted a similar shape of time course, but with a lesser magnitude and a peak value at month 1. 4. Anteiso- fatty acid reached the plateau level at month 5 and remained roughly constant through maturity to senescence. PMID- 1617944 TI - Effect of training on fibre composition and phosphate metabolites in rest measured in vitro in muscles of young pigs. AB - 1. Fibre type composition and phosphate metabolites were studied in m. longissimus thoracis (MLT), m. rectus femoris (MRF) and m. triceps brachii (MTB) in trained (N = 6) and sedentary (N = 6) pigs. 2. Samples were analyzed histochemically and by means of in vitro 31P NMR spectroscopy. 3. Training (duration 11 weeks) consisted of treadmill running at a speed of 1.1 m/sec. The daily exercise time of trained animals gradually increased from 10 min during the very first days to 60 min at the end of the 4th week. 4. During the final 7 weeks exercise time remained unchanged. Sedentary animals were not subjected to training. 5. A higher proportion of type beta R fibres in MRF, MTB and MLT and a lower proportion of type alpha W fibres were found in the trained group of animals compared to the control group. 6. In MLT no significant differences in the proportion of type alpha W were observed between both groups. 7. No significant differences in average fibre diameter of muscle fibres were found between groups. 8. No differences in concentration of phosphate compounds were observed between trained and sedentary groups. 9. Muscles with a higher proportion of type IIb fibres in both groups of pigs contained higher amounts of phosphocreatine (PCr) and were also characterized by a higher ratio of PCr to inorganic phosphate (Pi). PMID- 1617943 TI - Thiol groups and other chemical characteristics of rat monoclonal immunoglobulin A. AB - 1. Three aspects of the monoclonal rat IgA IR22 were investigated: its free thiol groups, its hinge structure and its glycopeptides. 2. Exposed thiol groups, 1.5 per IgA dimer, were located in the Fc region, and buried thiol groups, 3.2 per IgA dimer, were located in the Fd region. 3. Rat IgA was cleaved to Fab fragments by pepsin, but, unlike mouse IgA, it was not cleaved at the hinge region by papain. 4. The contents of GlcNAc indicated that there were two N-linked glycopeptides in the Fab region, and one in the Fc or tail regions. PMID- 1617945 TI - Fractionation of DNA from marine invertebrate (Maja crispata, Mytilus galloprovincialis) haemolymph by alkaline elution. AB - 1. An alkaline elution procedure for the detection of DNA damage in marine invertebrate haemolymph has been developed. 2. Provided that three criteria are optimized, such as buffer composition, small filter pores (0.22 microns GVWP 025 00, Millipore), and optimal amounts of haemolymph applied, flow rates may be changed within the range of 0.2 ml/min to 0.05 ml/min without adverse back pressure on the filter and without blocking filter pores. 3. Under optimal conditions, 70% of mussel haemolymph DNA, and 80% of crab haemolymph DNA will be retained on the filter after 6 hr of elution, indicating shorter DNA in mussel haemolymph. 4. The technique is applicable for testing the in vivo effects of different compounds on DNA in marine invertebrates, and to measurements of DNA damage in naturally exposed mussels. 5. This argues an important case for the use of alkaline elution technique for assessment of environmental genotoxicity, and especially for investigation of DNA damage in different marine organisms which cover a broad range in their DNA molecular weights. PMID- 1617946 TI - Functional and immunochemical comparison of hepatic UDP-glucuronosyltransferases in a piscine and a mammalian species. AB - 1. The aglycone specificity of hepatic microsomal glucuronidation was compared under uniform conditions in a fish, Pleuronectes platessa and a mammal, Rattus norvegicus, representative of the most primitive and advanced vertebrate classes. 2. Both species exhibited comparable UDP-glucuronosyltransferase (UDPGT) activity towards planar phenolic substrates (1-naphthol, 4-nitrophenol); however, plaice activity towards bulky non-planar substrates such as (-)-morphine was either 200 fold lower, or for an arylacetic acid (RS-2-phenylpropionic acid) and an aryloxyacetic acid (clofibric acid) non-detectable. 3. Conjugation of the endogenous substrates, bilirubin and steroids were 4- to 40-fold lower in the plaice than in the rat. Whilst both species formed diglucuronides of the asymmetrical bilirubin IX alpha, they displayed a reciprocal preference for the initial esterification, conjugation of the C-8 side chain predominating in the rat and of C-12 in the fish. 4. Immunoblot analysis using two polyclonal antisera preparations raised against rat UDPGTs demonstrated the presence of multiple weakly cross-reacting polypeptides in fish microsomes indicative of multiple isoforms and conservation of common structural motifs over more than 350 million years since evolutionary divergence of the mammals. PMID- 1617947 TI - Tumour-localizing properties of porphyrins. In vivo studies using free and liposome encapsulated aminolevulinic acid. AB - 1. Using different doses of free and liposome encapsulated aminolevulinic acid (ALA) (between 2 and 8 mg/animal), given i.p., s.c. and intra-tumoural (i.t.), in vivo porphyrin synthesis by tumour, red blood cells (RBC) and different organs from tumour-bearing mice (TBM) and normal mice (NM) at different times, up to 24 hr after ALA administration, was examined. 2. It was found that by giving entrapped ALA, at a dose of 6 mg/animal (or 200 mg/kg wt), after 10 hr, a high level of porphyrin accumulation in the tumour was produced (7 micrograms/g tissue). Low synthesis occurred in muscle, lung, brain, RBC and skin; in spleen, kidney and liver synthesis is significant after 10 hr, but after 24 hr returned to normal values in the spleen and to about 2-3 micrograms/g tissue in the kidney and liver. 3. The tumour/skin porphyrin concentration ratio after 10 hr was nearly 30, the highest so far reported. 4. These results support our previous in vitro findings, indicating that free or encapsulated ALA might be used for early diagnosis of cancer and in photodynamic therapy. PMID- 1617948 TI - A program to facilitate cytotoxicity assay data reduction. AB - A report of a program which performs the initial computational reduction of the raw data from a cytotoxicity assay and outputs the reduced data as an image of the arrangement of the assay(s) upon the microwell plate. The program accepts the raw data either as manual or diskette file input. PMID- 1617949 TI - MW/Pharm, an integrated software package for drug dosage regimen calculation and therapeutic drug monitoring. AB - The pharmacokinetic software package MW/Pharm offers an interactive, user friendly program which gives rapid answers in clinical practice. It comprises a database with pharmacokinetic parameters of 180 drugs, a medication history database, and procedures for an individual drug dosage regimen calculation. The included curve-fitting facilities allow estimation of pharmacokinetic parameters on the basis of medication history, taking into account a varying status of the patient with respect to body weight and kidney function, optionally using a Bayesian procedure. The module KinBes performs the evaluation of bioavailability studies, including various methods, and an extensive statistical evaluation of bioequivalence. PMID- 1617950 TI - Classification of chromatic visual evoked potentials with the aid of a neural net. AB - Twelve normal subjects, and six color blind (three protanopes and three deuteranopes) individuals were used in this study. Visual evoked potentials (50 150 msec post-stimulus) were recorded in response to three stimuli: (a) three horizontal, achromatic bars alternating in luminosity between bright and dim, (b) bars alternating between blue and red, and (c) bars alternating between green and red. The resulting waveforms were normalized in amplitude and submitted to a commercial neural net program for classification. The network correctly identified 24 of the 36 normal responses. (2) The network was also asked to distinguish between the responses of normal and color blind individuals. Based upon the blue/red response, the network correctly classed 12 of 18 responses, and based upon the green/red response correctly classified 14 of 18 (including all 6 color blinds). (3) These results are statistically highly significant and suggest that the VEP elicited by chromatic stimulation is substantially different from that elicited by achromatic stimuli. PMID- 1617951 TI - Automated recognition of corrupted arterial waveforms using neural network techniques. AB - A data acquisition system that automatically discards corrupted or undesirable signals would save untold hours of drudgery for researchers. Continuous recording of variables to provide detailed behavior patterns generates huge amounts of raw data. Unfortunately waveforms usually require visual inspection for isolating desired behavior or validating signal integrity. This tedious and time-consuming step can potentially be eliminated using a novel computer science technique. We have trained a simulated neural network to recognize corrupted arterial pressure waveforms. Our system can now evaluate the validity of the arterial waveform without human intervention with an average false positive error rate of 2.2% and an average false negative error rate of 12.6%. PMID- 1617952 TI - A PC program for growth prediction in the context of Rao's polynomial growth curve model. AB - We consider the problem of growth prediction in the context of Rao's [1] one sample polynomial growth curve model and provide a PC program, written in GAUSS, to perform the associated computations. Specifically, the problem considered is that of estimating the value of the measurement under consideration for a "new" individual at the Tth time point given measurements on that individual at T-1 previous points in time and the values of the measurement on N "similar" individuals at all T time points. The times of measurement t1, t2, . . ., tT need not be equally spaced, but we assume that each of the N individuals comprising the normative sample were measured at these times. The method and the program are illustrated using the leave-one-out method on a sample of N = 12 male rhesus monkeys whose mandibular ramus height was measured five times at yearly intervals. PMID- 1617953 TI - The French communicable diseases computer network: a technical view. AB - This paper describes an information system (IS) established in France in 1984 for the national surveillance of communicable diseases. This IS is based on a videotex server and a relational database management system. The videotex server is the IS front-end. It performs the following functions: interpersonal communications, synthetic information retrieval into an epidemiologic info-base and data entry owing to its specialized applications. The relational database management system allows the user to manage and consult an epidemiologic database updated in quasi-real time. Several specific tools have also been developed in order to enhance data representation and analysis and the decision support capabilities of the IS. PMID- 1617954 TI - A computerized documentation system for cancer pain management units. AB - A cancer pain management unit can benefit markedly from a well-planned documentation system for administrative and scientific purposes. This article presents the principles of such a computerized system based on relational data base programs. The described system has been used by the authors for the last seven years. The successful documentation of more than 1400 patients over treatment periods of up to 2 years has provided detailed administrative and scientific information. PMID- 1617955 TI - A computer program for planimetric analysis of digitized images. AB - Planimetrical measurements are made to calculate the area of an entity. By digitizing the entity the planimetrical measurements may be done by computer. This computer program was developed in conjunction with a research project involving measurement of the pneumatized cell system of the temporal bones as seen on X-rays. By placing the X-rays on a digitizer tablet and tracing the outline of the cell system, the area was calculated by the program. The calculated data and traced images could be stored and printed. The program is written in BASIC; necessary hardware is an IBM-compatible personal computer, a digitizer tablet and a printer. PMID- 1617956 TI - Elicitation of release of luteinizing hormone by N-methyl-d,l-aspartic acid during three paradigms of suppressed secretion of luteinizing hormone in the female pig. AB - Two experiments were conducted to determine the minimal effective dose during lactation and site of action of N-methyl-d,l-aspartic acid (NMA) for elicitation of release of luteinizing hormone (LH) in female pigs. In the first experiment, three doses of NMA were given to lactating primiparous sows in which endogenous LH was suppressed by suckling of litters. In the second experiment, ovariectomized gilts were pretreated with estradiol benzoate or porcine antisera against GnRH to suppress LH and then given NMA to determine if it elicited secretion of LH directly at the anterior pituitary or through release of GnRH. In experiment 1, 3 lactating sows (17 +/- 1.5 d postpartum) were each given three doses of NMA (1.5, 3.0 and 5.0 mg/kg body weight [BW]; IV) on 3 consecutive days in a Latin Square design. Blood samples were collected every 10 min from -1 to 1 hr from injection of NMA. NMA at 1.5 and 3.0 mg/kg did not affect (p greater than .5) secretion of LH; however, 5 mg NMA/kg elicited a 114% increase (p less than .001) in circulating levels of LH during 1 hr after treatment. In experiment 2, 8 ovariectomized gilts were given either estradiol benzoate (EB; 10 micrograms/kg BW; IM n = 4) to suppress release of GnRH or porcine antiserum against GnRH (GnRH Ab; titer 1:8,000; 1 ml/kg BW; IV; n = 4) to neutralize endogenous GnRH. Gilts infused with GnRH-Ab were given a second dose of antiserum 24 hr after the first. Gilts were then given NMA (10 mg/kg BW; IV) 33 hr after EB or initial GnRH-Ab. Blood samples were drawn every 6 hr from -12 to 24 hr from EB or GnRH-Ab treatments, and every 10 min from -2 to 2 hr from NMA. Serum LH declined (p less than .001) after EB (from 1.87 +/- .2 ng/ml at 12 hr before EB to 0.46 +/- .02 ng/ml during 24 hr after EB) and GnRH-Ab (from 1.97 +/- .1 to 0.59 +/- .02 ng/ml). In gilts treated with EB, the area under the curve (AUC) for the LH response (ng.ml-1.min) 1 hr after NMA (38.7 +/- 3) was significantly greater (p less than .01) than the 1 hr prior to NMA (21.3 +/- 1.5). Treatment with NMA had no effect (p greater than .5) on secretion of LH in gilts infused with GnRH Ab.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1617957 TI - Neuroendocrine regulation of growth hormone secretion in sheep. V. Growth hormone releasing factor and thyrotrophin releasing hormone. AB - The effects of intravenous (IV) and intracerebroventricular (ICV) administration of either bovine growth hormone releasing hormone (GRF) or thyrotrophin releasing hormone (TRH) on plasma growth hormone (GH) and glucose levels have been examined in sheep. Intravenous GRF 1-29NH2 at 3 and 30 micrograms stimulated an increase in GH levels in a dose-dependent fashion; administration of GRF into a lateral cerebral ventricle, however, produced a smaller GH response which was similar at these two doses. Evaluation of somatostatin levels in petrosal sinus blood (which collects pituitary effluent blood) showed that ICV administration of GRF stimulated a release of somatostatin into the blood. Furthermore, concurrent administration of GRF and a potent anti-somatostatin serum ICV resulted in a much enhanced release of GH which was similar to that obtained with a comparable dose of GRF given IV. TRH (as another putative GH-secretagogue) was also administered both IV and ICV. When given IV, 200 micrograms (but not 100 micrograms) TRH produced an elevation in GH levels. By contrast, when 5 micrograms TRH was given ICV there was a decrease in circulating GH levels, but no change in plasma somatostatin concentrations. These results indicate that the smaller GH response to ICV- compared with IV-administered GRF is due to the release of somatostatin within the brain. In addition, it would seem that TRH is not a physiological GH secretagogue in sheep. PMID- 1617958 TI - Effect of active immunization against growth hormone releasing factor on concentrations of somatotropin and insulin-like growth factor I in lactating beef cows. AB - Two experiments were conducted to determine the effects of immunoneutralization of growth hormone-releasing factor [GRF(1-29)-NH2] on concentrations of somatotropin (ST) and insulin-like growth factor I (IGF-I) in lactating beef cows. In Experiment 1, multiparous Hereford cows were immunized against 2 mg GRF(1-29)-(Gly)4-Cys-NH2 conjugated to human serum albumin (GRFi, n = 3) or 2 mg human serum albumin (HSAi, n = 3) at 52 +/- 1 d prior to parturition. Boosters (1 mg) were administered on days 12, 40 and 114 postpartum (pp). Serum samples were collected at 15-min intervals for 5 hr on days 18, 46 and 120 pp, followed by administration (IV) of an opioid agonist (FK33-824; 10 micrograms/kg) and an antagonist (naloxone; .5 mg/kg) at hours 5 and 7, respectively. A GRF-analog ([desamino-Tyr1, D-Ala2, Ala15] GRF (1-29)-NH2; 3.5 micrograms/kg) and arginine (.5 g/kg) were administered at hour 10 on days 47 and 121, respectively. Percentage binding of [125I]GRF (1:100 dilution of serum) 28 d after primary immunization was greater in GRFi (14.3 +/- 4.9) than in HSAi (.7 +/- .3) cows. Binding increased to 29.3 +/- 6.5% after first booster in GRFi cows. Episodic release of ST was abolished by immunization against GRF; concentration and frequency of release of ST were lower (P less than .05) in GRFi than in HSAi cows on all days pp. Concentrations of IGF-I were lower in GRFi than in HSAi cows throughout lactation. Serum ST failed to increase following FK33-824 or arginine in GRFi; however, ST increased after both compounds in HSAi cows. Concentrations of ST following GRF-analog were greater (P less than .05) in HSAi than in GRFi cows. Experiment 2 was conducted to determine if a lower dose of antigen and a single booster would be sufficient to lower ST and IGF-I in lactating cows. Multiparous Hereford and Angus cows were assigned to GRFi (n = 6) or HSAi (n = 6). Primary (1.2 mg) and booster (.5 mg) immunizations were administered -14 and 8 d from calving, respectively. Cows were restricted to 60% of recommended intake of energy during lactation in order to elevate concentrations of ST. Serum samples were collected at 15-min intervals for 6 hr on days 26, 50, 73, 90 and 109 pp. Two of six GRFi cows had binding less than 10% (1:1,000 dilution of serum) and were omitted from further analyses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1617959 TI - Effects of intracerebroventricular corticotropin-releasing hormone and intravenous morphine on cortisol, prolactin and growth hormone secretion in sheep. AB - It has previously been demonstrated that naloxone and morphine modify the adrenocortical and pituitary responses of sheep to stress. Since CRH acts within the brain to co-ordinate the stress response, the present experiment was conducted to determine whether morphine has similar effects in sheep given oCRH centrally. Plasma concentrations of cortisol, prolactin and growth hormone were measured in blood samples collected at 10 min intervals from sheep (N = 5) over a 3-hr period. Intravenous injections of saline vehicle or morphine sulphate (0.4 mg/kg) were given after 40 min and intracerebroventricular injections of oCRH (0, 5 or 20 micrograms) were administered after 60 min. Sustained, dose-related, increases in cortisol were induced by oCRH and, in agreement with findings in stressed sheep, these responses were reduced by pretreatment with morphine. Prolactin levels appeared to increase after morphine but oCRH, on its own, did not increase prolactin secretion in this study. There was no change in growth hormone concentrations after oCRH whereas morphine transiently stimulated release. PMID- 1617960 TI - Lack of a nocturnal rise of serum melatonin in prepubertal gilts. AB - Experiments were conducted to determine if a nocturnal rise in serum melatonin occurs in prepubertal gilts and whether acute exposure of gilts to light during the dark period abruptly reduces serum concentrations of melatonin. In experiment 1, 12 prepubertal crossbred gilts (Duroc x Hampshire x Chester White x Yorkshire) weighing 96.4 + 1.3 kg at 5.1 + .1 mo of age were housed in an LD cycle of 10:14. Following a 3-wk acclimation period, blood samples were drawn at 1-hr intervals from indwelling jugular catheters. Serum concentrations of melatonin were similar (P greater than .05) among blood samples collected during light and dark periods. In experiment 2, serum concentrations of melatonin did not change (P greater than .05) when gilts were abruptly exposed to light during the normal dark period. In experiment 3, serum concentrations of melatonin were similar (P greater than .05) in blood samples collected at 2-hr intervals under 700 lux of light or in total darkness from gilts maintained in either LD 9:15 or LD 24:0. Data from experiment 4 demonstrated that serum melatonin could be detected in nighttime samples if exogenous melatonin was ingested by gilts at night. Together, these experiments clearly indicate that prepubertal gilts do not exhibit a nocturnal rise in serum melatonin when maintained under short daylengths (10L:14D or 9L:15D), and serum melatonin concentrations are unaffected by abrupt changes in light/dark conditions. PMID- 1617961 TI - Serum hormone and metabolite concentrations in fasted young bulls and steers. AB - The effect of dietary energy restriction on serum insulin, insulin-like growth factor I (IGF-I), growth hormone, (GH), cortisol, plasma urea nitrogen (PUN) and nonesterified fatty acid (NEFA) concentrations was examined. Angus bulls and steers (10 mo) were allotted to two groups of 12 animals and assigned a treatment order. In a switchback design, animals in order 1 were fed a high grain diet, then fasted, while order 2 animals were fasted, and then fed. Animals were allowed 60 hr to acclimate between treatments. Serum and plasma were obtained at 20 min intervals and 60 min, respectively, for 6 hr after feeding and for the last 6 hr of a 30 hr fast. Serum was assayed for insulin, IGF-I, GH, and cortisol (total and free). Plasma was assayed for PUN and NEFA. Mean insulin (ng/ml) differed between fed (.95 +/- .08) and fasted (.26 +/- .08) animals (P less than 01). Both mean total and free cortisol (ng/ml) were lower in fed (11.48 +/- .99) (1.06 +/- .12) than in fasted (17.10 +/- .93) (1.62 +/- .12) animals, respectively (P less than .01). Animals in order 1 differed in mean IGF-I (ng/ml) between fed (199.0 +/- 8.0) and fasted (116.5 +/- 7.2) treatments (P less than .01). Mean IGF-I for animals in order 2 was 146.7 +/- 7.2 in fed and 213.9 +/- 7.2 in fasted animals (P less than .01). Mean GH did not differ between treatments. Mean PUN and NEFA were higher in fasted than in fed animals (P less than .01). Except for % free cortisol (P less than .05), the hormones did not differ between bulls and steers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1617962 TI - Six-month carbohydrate metabolism studies in women using oral contraceptives containing gestodene and ethinyl estradiol. AB - Twenty-five women had their carbohydrate metabolism prospectively evaluated during the six months that they used a gestodene and ethinyl estradiol monophasic oral contraceptive. Serum glucose and insulin levels were measured during a 75 gram three-hour oral glucose tolerance test. At the six-month test, the three hour glucose and the fasting and three-hour insulin values were significantly elevated. The literature on carbohydrate metabolism during gestodene oral contraceptive use is also reviewed. PMID- 1617963 TI - Removal of intrauterine devices with missing tails during early pregnancy. AB - During a 70-month period, CO2 hysteroscopy was carried out on 52 pregnant women wearing IUDs with retracted tails. Ultrasonography was done prior to hysteroscopy to determine the size of the gestational sac and the site of the device. Successful removal of the device occurred in 46 cases. The technique, the findings of the study, and the limitations of the procedure are described. PMID- 1617964 TI - Conditions for choosing between drug-induced and surgical abortions. AB - In France, pregnant women with amenorrhoea of no more than 49 days intending to terminate pregnancy can choose between a surgical abortion via vacuum aspiration under local or general anesthesia and a drug method combining Mifepristone orally administered (RU 486 degrees), with a prostaglandin analogue. This prospective survey was conducted to study the conditions under which women choose their abortion method, and to evaluate the acceptability of each method after the abortion. The data gathered from 488 women were analyzed according to their initial decision, and then according to the method actually used. The majority (62%) chose RU 486. The women's choice was found to be linked to sociodemographic characteristics such as age, education, occupation, geographic origin, and certain attitudes towards pregnancy, as well as to the individual criteria of each method. The women who chose the drug protocol had most often already made their decision before going to the family planning center (68%), having been advised by their doctor (20%). They were slightly less satisfied with the abortion experience than they had expected: 12.4% were unsatisfied in the RU group and 3.6% in the aspiration group. They needed more rest and quiet afterwards (50%) than the other women. They were distinguished by their desire to verify the expulsion (63%). The length of pregnancy is therefore not the only criterion to be considered when recommending one or other of these methods: the women concerned have different requirements and should have several possibilities to choose from. PMID- 1617965 TI - Serum nickel, copper and zinc in Norplant users. AB - Changes in serum nickel, copper and zinc were evaluated in 45 Norplant users. Two groups were selected for this study. Group I included 15 regularly menstruating females as controls and as short-term users (90 days after Norplant insertion). Group II included 30 Norplant users for one year or more as long-term users. These elements were determined by atomic absorption spectrophotometry. Serum nickel showed no significant change in short-term nor in long-term users when compared to the control group or to each other. Serum copper and zinc revealed a significant increase in short-term users for a short period of time, which returned to normal levels in long-term users. There was disappearance of the cyclic changes in serum copper and zinc concentrations on comparing their levels in ovulatory to non-ovulatory Norplant users. The use of Norplant has no deleterious effects on serum levels of nickel, copper and zinc. PMID- 1617966 TI - Serum and endometrial sodium and potassium levels with inert and copper containing IUCDs and relation to serum steroid levels. AB - Serum and endometrial sodium (Na) and potassium (K) levels and serum estradiol, progesterone, testosterone and cortisol were measured in the mid-follicular and mid-luteal phases of the menstrual cycle in 20 Lippes loop and 20 CuT-200 IUCD users and 20 matched controls. Na and K were measured by atomic absorption spectrophotometry, while serum steroids were measured by RIA. Regarding steroids, the only significant difference between the three groups was a significantly lower mean mid-luteal serum estradiol in CuT-200 IUCD users compared to Lippes loop users (p less than 0.05). Regarding sodium in the control group, there was significantly lower mean mid-luteal serum and endometrial Na (p less than 0.01) that was not found in both groups of IUCD users. In the mid-follicular phase, there was significantly higher mean serum Na in both Lippes loop and CuT-200 groups compared to controls (p less than 0.05). Mean endometrial Na showed no significant difference between the three groups in both phases of the menstrual cycle. Regarding potassium in the control group, there was significantly lower mean levels in the mid-luteal-phase of the cycle (p less than 0.01) that was not seen with both groups of IUCD users. Serum K showed no significant difference in the three groups in both phases of the menstrual cycle. Endometrial K showed a significantly higher mean level in both Lippes loop and CuT-200 IUCD users compared to controls in the mid-luteal (p less than 0.01), but not in the mid follicular phases of the cycle. PMID- 1617967 TI - Hormonal profile of the menstrual cycle in Chinese women after tubal sterilization. AB - Ten women after tubal sterilization were studied for the hormonal profile of the menstrual cycle. They had undergone sterilization procedures, on the average 5.3 years (range 1.5-10 years) earlier. The serum concentrations of LH, FSH, prolactin, estradiol and progesterone were measured by RIA in daily blood samples of a complete menstrual cycle. Another ten normal women were studied at the same time and were used as the control group. There were no significant differences in the hormonal patterns of the menstrual cycle between the two groups. There was a significantly lower LH level in the early luteal phase of the tubal ligation group compared to the control group. Also, a significantly lower E2 luteal peak compared to the preovulatory peak was observed in the tubal ligation group. The physiological significance of these minor changes is not clear. Only one out of ten women in the tubal ligation group, who had undergone sterilization 1.5 years prior, showed a deficiency in luteal function, but her ovulatory function and menstrual cycle appeared normal. This study indicates that normal hormonal profiles are retained after tubal sterilization. PMID- 1617968 TI - Conducting a hospital-based case-control study of the relationship between vasectomy and cardiovascular disease in Korea--an experience in an Asian setting. AB - An increasing number of case-control studies are being performed in the developing world. This paper describes the difficulties and advantages the author has experienced in conducting a hospital-based case-control study in the Republic of Korea testing the hypothesis of whether vasectomy is associated with subsequent cardiovascular disease. This experience should provide a useful reference for researchers planning studies using a similar approach in an Asian setting. PMID- 1617969 TI - Pregnane derivatives as pregnancy interceptive agents: efficacy determination on growing trophoblasts (in vitro) and in pregnant hamsters (in vivo). AB - An in vitro test system was standardized to study potentiality of five hormonally inert pregnane derivatives on growing trophoblasts isolated from ectoplacental cone (EPC) of day 8 hamster embryo. Cells were incubated with different concentrations of respective compounds in surface droplets. The response was determined by analyzing the sequence of changes in cell morphology like attachment, growth, proliferation, differentiation and/or degeneration within 24 or 48 h following seeding. The in vivo efficacy of these compounds was determined in hamster during peri- and immediate post-implantation periods (days 3-8 post coitum). Two compounds 88/583 and 88/585 were found to inhibit not only growth and proliferation of the cells but caused total degeneration within 24 h. The same compounds induced partial to complete resorption of the foetuses in treated animals. Whereas, the other three compounds 88/506, 88/594 and 89/43 that showed lack of comparable potentiality in vitro were found to be equally ineffective in vivo. The results indicate a positive correlationship between in vitro and in vivo activity. PMID- 1617970 TI - Pressure-flow relationships of the pulmonary circulation during endotoxin infusion in intact dogs. AB - BACKGROUND AND METHODS: We aimed to characterize the effects of an endotoxin insult (Escherichia coli 0127:B8) on the relationships between pulmonary vascular pressure and flow in intact dogs. To achieve this goal, multipoint plots of total pressure gradient, arterial pressure gradient, and venous pressure gradient vs. flow were generated by graded inflation of a right atrial balloon, which was used to vary flow. The partitioning of the total pressure decrease across the pulmonary vasculature (total pressure gradient = pulmonary arterial pressure pulmonary artery occlusion pressure [PAOP]) into gradients across pulmonary arterial (arterial pressure gradient = pulmonary arterial pressure--effective capillary pressure) and pulmonary venous (venous pressure gradient = effective capillary pressure--PAOP) regions was assessed by a waveform mathematical analysis of the pulmonary arterial pressure profile during arterial occlusion, with computation of both PAOP and effective pulmonary capillary pressures. Slopes and extrapolated pressure intercepts from linear regression fits to the pulmonary vascular pressure/flow plots were determined in seven dogs after a 2-hr endotoxic infusion interval and were compared with the corresponding values that characterized a similar group of sham-operated dogs. RESULTS: Under normal conditions, the extrapolated pressure intercept for pulmonary arterial pressure gradient was virtually 0 mm Hg; for total pulmonary arterial pressure gradient and pulmonary venous pressure gradient, the mean extrapolated pressure intercepts were substantially positive: 2.4 +/- 0.2 and 2.1 +/- 0.3 mm Hg, respectively. Endotoxin infusion at 0.25 micrograms/kg/min significantly increased the pressure intercepts from 2.4 to 8.7 and from 2.1 to 8.3 mm Hg of total pressure gradient and venous pressure gradient vs. flow, respectively. This infusion produced a minor, nonsignificant change in the intercept of arterial pressure gradient vs. flow, whereas it increased its slope significantly (p less than .05) from 0.036 to 0.081 mm Hg/mL/min/kg. CONCLUSIONS: These data suggest that endotoxin's effects on vascular resistance are exerted at two different loci such that these effects are additive. These endotoxin-induced effects consisted of increased vascular resistance of the arterial segment and appearance of a Starling resistor at the venous side of the pulmonary circulation, which acted as the relevant back pressure to flow. PMID- 1617971 TI - Hemodynamic and metabolic effects of epinephrine during cardiopulmonary resuscitation in a pig model. AB - BACKGROUND AND METHODS: This study was designed to assess the effect of epinephrine during cardiopulmonary resuscitation (CPR) on left ventricular myocardial blood flow, systemic oxygen delivery and consumption, and on plasma glucose and lactate concentrations. Fourteen pigs were allocated to receive either 0.9% saline (n = 7), or 45 micrograms/kg epinephrine (n = 7) after 5 mins of ventricular fibrillation, and 3 mins of open-chest CPR. Left ventricular myocardial blood flow was measured with radiolabeled microspheres. Plasma catecholamine concentrations were measured by high-pressure liquid chromatography. RESULTS: During open-chest CPR, mean (+/- SD) values of left ventricular myocardial blood flow before, 90 secs, and 5 mins following drug administration were 49 +/- 10, 46 +/- 12, 43 +/- 15 mL/min/100 g, respectively, in the control group, and 52 +/- 12, 118 +/- 21, 84 +/- 28 mL/min/100 g, respectively, in the epinephrine group (p less than .05 at 90 secs and 5 mins). At the same time points, mean (+/- SD) oxygen delivery indices were 7.7 +/- 3.0, 6.0 +/- 2.1, 6.5 +/- 2.7 mL/min/kg in the control group and 7.6 +/- 2.5, 5.3 +/- 2.1, 5.5 +/- 1.9 mL/min/kg in the epinephrine group (nonsignificant). Mean oxygen consumption indices were 5.8 +/- 2.4, 4.6 +/- 1.6, 5.2 +/- 2.6 mL/min/kg in the control group and 5.4 +/- 1.6, 4.2 +/- 1.6, 4.4 +/- 1.4 mL/min/kg in the epinephrine group (nonsignificant). During CPR and before epinephrine administration, arterial plasma epinephrine concentrations increased from prearrest values of 0.77 +/- 0.70 to 62.1 +/- 48.7 micrograms/L, and plasma norepinephrine concentrations increased from 0.28 +/- 0.32 to 104.3 +/- 57.1 micrograms/L. After administered epinephrine, there was an additional increase to 271 +/- 83 micrograms/L at 90 secs in arterial plasma epinephrine, but no important alteration in the plasma norepinephrine concentration. At no time point could we find a clinically important difference in plasma glucose or lactate concentrations between the two groups. CONCLUSIONS: At a dose of 45 micrograms/kg, epinephrine caused an increase in left ventricular myocardial blood flow after a total of 8 mins of cardiac arrest, including 3 mins of CPR, while not altering systemic oxygen delivery and consumption, plasma glucose, or lactate concentrations. PMID- 1617972 TI - Advance directives: implications for critical care. AB - OBJECTIVE: To discuss the relative merits and limitations of living wills and the durable power of attorney for health care. DATA SOURCES: Computerized search of MEDLINE. STUDY SELECTION: Studies involving treatment decisions at the end of life and descriptive articles on advance directives. RESULTS: The recent Cruzan case and passage of the Patient Self-Determination Act have led to an ethical and legal recognition of advance directives, and therefore, critical care practitioners must be familiar with these documents. A living will is a mechanism by which patients can communicate their desires for medical treatment at the end of life. However, the condition that patients be in a "terminal condition," the inability to predict every possible clinical circumstance, and linguistic vagueness have limited the usefulness of living wills. The durable power of attorney for health care overcomes the inherent restrictive weaknesses of living wills, because informed decisions are made by people based on their knowledge of the patient's beliefs and the nuance of the clinical scenario. A concern with this advance directive is that some patients may not know a suitable person to appoint or that the chosen agent may not be available. CONCLUSIONS: We recommend the execution of both a living will and a durable power of attorney for health care to provide the best assurance that patients' desires concerning medical treatments will be respected. PMID- 1617973 TI - Acute care research: is it ethical? AB - BACKGROUND: Research in acute care is a troubling area for Institutional Review Board (IRB) approval and informed consent. Confusion about ethical and legal requirements has hampered research efforts and subsequent patient benefits. ANALYSIS: Acute care patients are the relatively few critical care patients who have suffered unexpected events that carry a high probability of mortality or severe morbidity unless immediate medical intervention is provided. We argue that acute care research is justified if the usual ethical requirements for research are modified to reflect the uniqueness of the situation. CONCLUSIONS: Our recommendations are to: a) use an explicit definition of acute care as distinct from other modes of critical care; b) eliminate the requirement for informed consent (as it is usually understood); and c) require stringent IRB oversight, regarding the unique ethical problems raised by this area of research. We further suggest that IRB oversight includes review of the protocol by a panel of individuals who represent possible enrollees in the proposed study. PMID- 1617974 TI - A clinical librarian program in the intensive care unit. AB - OBJECTIVES: Clinical decision-making in the intensive care setting frequently requires the physician to obtain additional resource information. Physicians typically consult with colleagues, use personal medical books or files, or use library materials. Clinical librarians may also be used. This study evaluates the effectiveness of an ongoing clinical librarian program in the intensive care setting. DESIGN/SETTING: During a 3-month period, house officers in the medical and coronary ICUs in a major teaching hospital asked the clinical librarian 66 patient-care questions. Attached to the information selected by the clinical librarian was a questionnaire asking how the information was applied. MAIN RESULTS: There was an overall response rate of 65.1%. House officers indicated that the information: a) aided in diagnosis (37.2%), b) contributed to a better understanding of the therapy (51.2%), and c) resulted in improved patient management (30.2%). In some instances, the information was multibeneficial. The clinical librarian spent an average of 47 mins/question, and accumulated an average computer charge of $3.59. Personnel and on-line charges over the 3-month study period averaged $45/question. CONCLUSIONS: Clinical librarian programs may deliver patient-specific information in a timely, cost-effective manner. This information has an impact in the intensive care setting. PMID- 1617975 TI - Pulmonary capillary pressure: a review. AB - OBJECTIVES: To demonstrate the importance of a) measuring effective pulmonary capillary pressure and b) evaluating the longitudinal distribution of pulmonary vascular resistance relative to pre- and postcapillary resistances. To review the development of methods used to determine pulmonary capillary pressure in experimental animal and clinical studies. DATA SOURCES: Human, animal, and modeling studies published since 1966 identified through MEDLINE and a review of bibliographies of relevant articles. STUDY SELECTION AND DATA EXTRACTION: All studies identified were reviewed with an emphasis on recent studies and those studies identifying various methodologies used to determine capillary pressure. Experimental studies were selected for their historical value and applicability to the clinical setting. DATA SYNTHESIS: Different models of the pulmonary circulation have been proposed. The electrical circuit model, which incorporated capacitance elements and two or four resistive elements, has been the basis for the determination of pulmonary capillary pressure in isolated lungs and in situ lungs in animals and patients. Methods used to determine pulmonary capillary pressure from a pulmonary arterial pressure tracing after balloon occlusion are: a) division of waveform into two components and logarithmic extrapolation of the slow component to occlusion time; b) visual determination of the pressure inflection point of the pulmonary arterial pressure tracing; and c) computer processing of the total arterial pressure transient. Both ease of calculations and difficulties can arise when each method is used. CONCLUSIONS: Pulmonary capillary hydrostatic pressure is an important determinant of pulmonary edema especially in the setting of pulmonary hypertension and adult respiratory distress syndrome. Hypoxia, sepsis, cardiac valvular disease, and inflammatory mediators produce variable changes in the longitudinal distribution of pulmonary vascular resistance so that an increased capillary pressure cannot be predicted by the pulmonary arterial or occlusion pressure. For proper therapy aimed at decreasing pulmonary vascular resistance, it is important to determine whether or not the particular therapy increases capillary pressure. Pulmonary capillary pressure is the most important determinant of lung fluid balance and is the major physiologic parameter that should be measured when various forms of plasma volume expansion and pulmonary vasodilators are used in the critically ill patient. PMID- 1617976 TI - Guidelines for the care of patients with hemodynamic instability associated with sepsis. Guidelines Committee; Society of Critical Care Medicine. PMID- 1617977 TI - Use of isoflurane for sedation in intensive care. PMID- 1617978 TI - Traumatic mitral insufficiency complicating blunt chest trauma treated medically: a case report and review. PMID- 1617979 TI - Periportal tracking on computed tomography scan diagnostic of extensive liver injury in a neonate. PMID- 1617980 TI - Gastric mucosal pH as a prognostic index of mortality in critically ill patients. PMID- 1617981 TI - Demystification of the septic response. PMID- 1617982 TI - Giants of critical care: a tribute to Max Harry Weil, MD, PhD. PMID- 1617983 TI - Antioxidant treatment with N-acetylcysteine during adult respiratory distress syndrome: a prospective, randomized, placebo-controlled study. AB - OBJECTIVE: To examine whether the antioxidant N-acetylcysteine could ameliorate the course of the adult respiratory distress syndrome (ARDS) in man. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Medical and surgical ICU in a regional hospital. PATIENTS: Sixty-six ICU patients with ARDS. INTERVENTIONS: Patients with ARDS (PaO2/FiO2 ratio less than 250 torr) were treated with either the antioxidant N-acetylcysteine 150 mg/kg as a loading dose and then 20 mg/kg/hr, or with placebo for 6 days. MEASUREMENTS AND MAIN RESULTS: No improvement could be demonstrated in the PaO2/FiO2 ratio in the study group as compared with the control group on any day. Pulmonary compliance was higher in the N-acetylcysteine group than in the placebo group on all days, but this difference did not reach the chosen 5% level of significance. No difference between the two groups could be demonstrated on chest radiograph or on survival rate. We documented that N-acetylcysteine acts as an anticoagulant and perhaps decreases pulmonary fibrin uptake during ARDS. CONCLUSIONS: N-acetylcysteine might be of benefit in ARDS. Before further clinical studies are started, problems with N-acetylcysteine and coagulation have to be elucidated in order to find out whether N-acetylcysteine could have a beneficial effect in the treatment of ARDS. PMID- 1617984 TI - Measurement of alveolar gas mixing in mechanically ventilated patients. AB - OBJECTIVE: To evaluate a computer-based, real-time, multibreath nitrogen washout technique in mechanically ventilated patients, incorporating an in-line flow measurement device to measure functional residual capacity and two indices of gas mixing, ventilatory efficiency, and alveolar mixing efficiency. SETTING: ICU, Charing Cross Hospital, London. DESIGN: Within-patient reproducibility of a multibreath nitrogen washout technique. PATIENTS: Seven intubated patients requiring mechanical ventilation. One patient completed two sets of readings. INTERVENTIONS: Patients were connected to a pneumatically driven ventilator fitted with a switching device to be operated either by an appropriate oxygen nitrogen mixture or equivalently blended oxygen-argon mixture. An inspiratory expiratory, two-way valve was attached to the delivery port of the ventilator, with a pneumotachograph for flow measurement and a gas sampling probe for gas concentration measurement in line with the patient's endotracheal tube. The analog signals were digitized and handled by a microcomputer. MEASUREMENTS AND MAIN RESULTS: No significant differences were found for any index, with coefficients of variation of 1.5%, 2.9%, and 2.1% for functional residual capacity, ventilatory efficiency, and alveolar mixing efficiency, respectively. CONCLUSIONS: This method gives excellent reproducibility for biological measurements in a clinical setting and shows that these measurements can readily be made on mechanically ventilated patients. PMID- 1617985 TI - Evaluation of right heart catheterization in critically ill patients. Ontario Intensive Care Study Group. AB - OBJECTIVE: To determine physicians' assessment of the therapeutic effect and patient benefit of data obtained from right heart catheterization. DESIGN: Before/after study. SETTING: One medical and one surgical academic ICU in two medical centers. PATIENTS: A total of 107 critically ill patients with uncertain hemodynamic status. DATA COLLECTION: Physicians looking after the patients were asked to evaluate the extent to which results of right heart catheterization resulted in changes in therapy and outcome. The same questions were asked of academic intensivists, two of whom reviewed each chart. RESULTS: Agreement regarding whether right heart catheterization had changed therapy was poor (chance corrected agreement [kappas] of -0.02 to 0.33). Treating physicians were more inclined than chart reviewers to conclude that management changes based on right heart catheterization improved outcome. Agreement on which patients benefited was poor (kappas of 0.03 to 0.32). CONCLUSIONS: Physicians' assessment of the effect of right heart catheterization on treatment decisions and patient outcomes is not reliable. Credible information regarding the benefits of right heart catheterization will require randomized trials. PMID- 1617986 TI - Blood vitamin concentrations during the acute-phase response. AB - OBJECTIVES: To investigate the effect, if any, of the acute-phase response on blood vitamin concentrations and to test the hypothesis that these concentrations may change during stress. DESIGN: Open study, utilizing a volunteer sample of patients. SETTING: Tertiary care center. PATIENTS: Twenty-six healthy adult volunteers (14 female and 12 male); 25 volunteers underwent uncomplicated orthopedic surgery and one suffered traumatic limb fractures. INTERVENTIONS: None. MAIN OUTCOME MEASUREMENTS: The presence of a systemic acute-phase response was documented by the determination of serum C-reactive protein concentrations. Blood vitamin concentrations were determined from sequentially collected blood samples over a 7-day period, and compared with entry values. RESULTS: The presence of the acute-phase response was documented by significant and transient increases in C-reactive protein values. This response was accompanied by significant and transient decreases in the concentrations of leukocyte vitamin C, and in plasma concentrations of vitamin A, retinol-binding protein, vitamin E, total lipids, pyridoxal-5'-phosphate, and albumin. Blood concentrations of pyridoxal-5'-phosphate, retinol-binding protein, and leukocyte vitamin C decreased to values below the respective normal ranges. These concentrations normalized without any therapeutic interventions. CONCLUSIONS: We demonstrated transient, but significant, decreases in blood vitamin concentrations during the acute-phase response. Recommendations regarding daily supplementation with these vitamins in clinical practice cannot be made on the basis of these results, as the functional importance of these observations is not, at present, clear. However, what is clear is that biochemical vitamin concentrations, determined during the acute-phase response, should be interpreted with care. PMID- 1617988 TI - Metabolic requirements in tetanus. AB - OBJECTIVE: To measure the metabolic requirements of patients with severe tetanus who require mechanical ventilation. DESIGN: Prospective, consecutive, open study using routine monitoring. SETTING: A multidisciplinary ICU in a large teaching hospital. PATIENTS: Five consecutive patients (age range 30 to 54 yrs) with severe tetanus. Four patients had clinical evidence of sympathetic nervous system overactivity. INTERVENTIONS: All patients were mechanically ventilated and appropriately treated for severe tetanus. Sympathetic nervous system overactivity was reduced by the administration of sedatives. MEASUREMENTS AND MAIN RESULTS: Measurements of metabolic rates were made using an indirect calorimetry device. Each of the five patients had three 8-hr periods of continuous metabolic monitoring for each of three levels of daily enteral nutritional support. The measured metabolic rates varied from 1310 to 2050 kcal/24 hrs (predicted 1280 to 1770 kcal/24 hrs). The variations from predicted basal metabolic rates varied from -6.3% to +10.5%. CONCLUSIONS: The measured metabolic rates of patients with severe tetanus who are appropriately sedated are relatively constant and are within 10.5% of the predicted basal metabolic rates. PMID- 1617987 TI - Cardiac vagal tone predicts outcome in neurosurgical patients. AB - OBJECTIVE: To evaluate the relationship between presurgical levels of cardiac vagal tone and outcome in neurosurgical patients. DESIGN: Prospective series. SETTING: Respiratory ICU in a university hospital. PATIENTS: Fifty-one adults admitted to the respiratory ICU between 1982 and 1985. Forty-two patients were scheduled for elective neurosurgery, and nine patients suffered from head trauma. INTERVENTIONS: Ten minutes of electrocardiographic (EKG) data were recorded before medical intervention. Neurosurgical patients scheduled for surgery had EKG data recorded 24 hrs before their operation. Trauma patients had EKG data recorded immediately after arrival in the respiratory ICU. MEASUREMENTS AND MAIN RESULTS: Cardiac vagal tone was evaluated using a vagal tone index, quantified from the EKG. Cardiac vagal tone monitored before surgical intervention significantly distinguished between the outcome groups only for the elective neurosurgical patients. Age, gender, heart rate, Glasgow Coma Scale scores, and tumor location, size, and malignancy were not related to outcome in the elective neurosurgery group. However, within the trauma group, low Glasgow Coma Scale scores were significantly related to poor outcome. CONCLUSIONS: Cardiac vagal tone may offer important predictive value by alerting the physician to the functional consequence of head injury. Information relating to autonomic nervous system functioning, such as the vagal tone index used in this study, may provide additional information that will complement the computed tomography scan results. This study demonstrates that the vagal tone index is a predictive factor that may be efficiently extracted from the heart rate pattern routinely monitored in ICUs. PMID- 1617989 TI - A novel score for predicting the mortality of septic shock patients. AB - OBJECTIVE: To establish a prognostic scoring system for septic shock patients. DESIGN: The clinical, biological, and hemodynamic data of these patients were retrospectively explored to select variables independently associated with outcome. According to the risk of death, ratings from 0 to 2 points were attributed to each value. SETTING: Medical intensive care service of a 1,000-bed tertiary care university medical center. PATIENTS: Eighty-eight patients in septic shock in whom hemodynamic measurements were performed using pulmonary artery flotation catheters. RESULTS: Fourteen clinical, biological, and hemodynamic variables were selected and rated for each patient. A Simplified Septic Shock Score, available immediately after admission and catheterization, was established by adding the rates of these variables. The mean Simplified Septic Shock Score was 2.5 +/- 1.7 (SD) in 43 survivors and 6.5 +/- 2.3 in 45 nonsurvivors (p less than .0001). Some underlying diseases and characteristics of infections also correlated with the outcome. Further ratings from 0 to 2 points were attributed to these conditions. A Complete Septic Shock Score was calculated by adding these rates to the Simplified Septic Shock Score. The Complete Septic Shock Score had a slightly better prognostic value than the Simplified Septic Shock Score, but it could be determined only after the availability of the microbiological data. The mean Complete Septic Shock Score was 3.1 +/- 1.9 in survivors and 8.4 +/- 2.6 in nonsurvivors (p less than .0001). Both Simplified and Complete Septic Shock Scores showed better association with patient outcome than the Simplified Acute Physiology Score or the Acute Physiology and Chronic Health Evaluation (APACHE II) score. CONCLUSIONS: The Simplified and the Complete Septic Shock Scores are simple scoring systems that appear to predict the outcome of septic shock patients more accurately than general scoring systems, such as the Simplified Acute Physiology Score and APACHE II score. These septic shock scores might be useful in assessing the severity of septic shock patients. PMID- 1617990 TI - Nonphysician transport of intubated pediatric patients: a system evaluation. AB - OBJECTIVE: To evaluate the occurrence of complications and patient deteriorations during the air and ground transportation of intubated pediatric patients, performed by a nonphysician-based team under the direction of an intensive care attending physician or fellow. DESIGN: Retrospective chart review. SETTING: A 600 bed university hospital with a 16-bed neonatal ICU and a 12-bed pediatric ICU. PATIENTS: All intubated pediatric patients (422 of 614 patients transported during the study period) transported by the dedicated neonatal/pediatric transport team from April 1988 to April 1990. MEASUREMENTS AND MAIN RESULTS: The transport records of intubated pediatric patients were abstracted. Recorded data included age, weight, gestational age, vital signs, diagnosis, interventions received, and use of paralytic agents and sedatives/analgesics. Patients were analyzed in three groups: group 1 (n = 295) included neonates; group 2 (n = 66) included patients greater than 1 month and less than 1 yr of age; and group 3 patients (n = 61) were ages greater than 1 yr. Group 1 had nine (3.1%) complications or patient deteriorations; four (1.4%) were related to the endotracheal tube. Group 2 had one (1.5%) airway complication and one deterioration. Group 3 had no complications or deteriorations. All but one of the airway complications were effectively handled by the transport team. At the referring hospital, the transport nurse or respiratory therapist intubated 62 (19.8%) patients in group 1, five (7.5%) in group 2, and three (4.9%) patients in group 3. Sixty-seven (23%), 21 (32%), and 30 (49%) patients of groups 1, 2, and 3, respectively, were paralyzed for transport. No complications were secondary to the use of paralytic agents or sedatives. CONCLUSIONS: Under proper medical guidance, well-trained nonphysician personnel can provide low-risk transport of intubated pediatric patients. Use of sedatives and paralytic drugs did not increase the risk of complications or patient deterioration. PMID- 1617991 TI - Outcome in critical care patients: a multivariate study. AB - OBJECTIVE: To identify patient variables that were significantly associated with outcome in the ICU. DESIGN: Retrospective chart study of ICU patients. SETTING: Letterman Army Medical Center, Presidio of San Francisco. PATIENTS: A total of 110 consecutive patients who remained in the ICU for greater than 72 hrs. METHODS: Univariate analysis of 26 input variables, representing physiologic status and chronic health assessment at the time of ICU admission of the patients, and adverse events that occurred during their ICU stay. The dependent variable assessed was the outcome of patients after ICU intervention. A bad outcome included patient mortality or discharge from the ICU in worse condition or in a chronic vegetative condition. Five selected input variables were used in a multivariate logistic regression analysis to identify independent predictors of a successful outcome. RESULTS: Univariate statistical techniques comparing the values of 26 input variables of patients who improved during their ICU stay (46 patients) with those values of patients who did not improve (52 deaths and 12 unimproved patients) indicated that the following nine variables were significantly different in these two groups: a) age (p = .04), b) acute physiologic score (p = .047), c) Acute Physiology and Chronic Health Evaluation (APACHE II) score (p = .040), d) the number of repeat ICU admissions during a given hospitalization (p = .019), e) development of respiratory complications while in the ICU (p = .033), f) sepsis developing while in the ICU (p = .0001), g) renal failure developing while in the ICU (p less than .0001), h) disseminated intravascular coagulation while in the ICU (p = .0028), and i) the occurrence of any iatrogenic complication while in the ICU (p less than .0001). Five of these nine variables were used in a stepwise logistic regression analysis to develop a model to predict ICU outcome. This model showed the following three variables to be significantly associated with unfavorable ICU outcome: a) occurrence of any iatrogenic event while in the ICU (p less than .001), b) development of renal failure in the ICU (p = .001), and c) occurrence of sepsis while in the ICU (p = .042). A common iatrogenic complication associated with unfavorable ICU outcome was related to drug therapy (frequently aminoglycoside toxicity). Twenty-one iatrogenic drug complications occurred in 64 patients who did not improve in the ICU, whereas only three iatrogenic drug complications occurred in 46 patients who improved (p less than .001). CONCLUSIONS: For patients who remain in the ICU for greater than 72 hrs, events occurring after ICU admission are negatively associated with ICU outcome, more so than ICU admission status as reflected by such indices as APACHE II scores. Iatrogenic complications, often due to inappropriate drug therapy, have a significant association with adverse outcome by multivariate analysis. We suggest that iatrogenic complications influence ICU outcome, and that they are potentially preventable. By lessening their frequency, ICU outcome may be improved. PMID- 1617992 TI - Tissue oxygenation during liver transplantation. AB - OBJECTIVES: a) To assess perioperative changes in tissue oxygenation parameters during liver transplantation; b) to evaluate the need for venovenous bypass as hemodynamic support; and c) to assess the efficacy of mixed venous oxygen saturation monitoring and the importance of lactate determinations in the management of patients following liver transplantation. DESIGN: Prospective case series. SETTING: Liver transplant unit in a university hospital. PATIENTS: A total of 68 consecutive patients undergoing liver transplantation. The entire population was analyzed before and after transplantation, dividing the patients into two groups, based on whether their initial cardiac index was higher (n = 37) or lower (n = 31) than 4.5 L/min/m2. MEASUREMENTS: Hemodynamic measurements and blood gas analyses were made before incision, before vascular clamping (including hepatic artery, portal vein and inferior vena cava), during the anhepatic phase, and at 5, 30, 60, and 120 mins following unclamping. Oxygen transport and oxygen consumption values were calculated. Serum lactate concentrations were measured by enzymatic technique. MAIN RESULTS: Mixed venous oxygen saturation was correlated with oxygen transport (Do2) in the whole population in which an abnormal oxygen consumption (Vo2)-Do2-dependent relationship occurred from the beginning of operation until 30 mins following unclamping. The comparison between hyperdynamic patients (initial cardiac index greater than 4.5 L/min/m2) with impaired tissue oxygenation and normodynamic patients showed that mixed venous oxygen saturation failed to correlate with Do2 when the cardiac index was greater than 4.5 L/min/m2 and that the Vo2-Do2 dependency was only noted in these patients. The serum lactate concentrations were similar in both groups. CONCLUSIONS: The Vo2-Do2 dependent relationship and mixed venous oxygen saturation-Do2 correlation noted in the 68 studied patients suggest the need for venovenous bypass and the reliability of mixed venous oxygen saturation monitoring in all patients scheduled for liver transplantation. However, a sharper comparison between hyperdynamic and normodynamic patients demonstrated the lack of efficacy of mixed venous oxygen saturation monitoring in predicting adequate tissue oxygenation in the first group and the mandatory need for venous shunting to limit tissue hypoxia which occurred despite its use only in these patients. Lactic acidosis appeared similarly in both groups and could not be linked to tissue hypoxia. PMID- 1617993 TI - Prolonged ventilatory support after open-heart surgery. AB - OBJECTIVES: To characterize the course of open-heart surgery patients who require prolonged (greater than 72 hrs) mechanical ventilation and to define the role and timing of tracheostomy. DESIGN: Retrospective review. SETTING: Cardiac surgery ICU and surgery wards at a university hospital. PATIENTS: All open-heart surgery patients during an 18-month period from January 1988 to July 1989 (n = 581). From this group, 58 patients (9.9%) required prolonged mechanical ventilation. INTERVENTIONS: Study patients (n = 58) were followed through the course of intubation and/or tracheostomy until they were extubated, left the hospital on ventilation, or died. MEASUREMENTS AND MAIN RESULTS: End-points for mortality and complications were determined. Overall mortality rate was 43% in the patients who required prolonged mechanical ventilation. Twenty-eight percent of the 58 patients died within the first 14 days. Of those patients who survived, 55% required an endotracheal tube only and were extubated in less than 14 days; 45% of the patients required tracheostomy. Of those patients who required tracheostomy, five (26%) were eventually extubated, seven (37%) remained mechanically ventilated, and seven (37%) died. The complication rate for endotracheal tubes was 65%; the complication rate for tracheostomy was 37%. CONCLUSIONS: Open-heart surgery patients requiring prolonged mechanical ventilation are a desperately ill subset of cardiac surgery patients. Those patients who survive are either extubated in less than 14 days or require prolonged mechanical ventilation beyond that point. In our opinion, patients should be given 1 wk to recover and one trial of weaning from the ventilator. If this approach fails, then they should undergo elective tracheostomy. PMID- 1617994 TI - Effect of septic serum on vascular smooth muscle: in vitro studies using rat aortic rings. AB - BACKGROUND AND METHODS: Septic shock in humans is characterized by hypotension, low systemic vascular resistance, and high cardiac output. We hypothesized that circulating vasodilatory substances are, in part, responsible for this low systemic vascular resistance. To investigate this possibility, we exposed isolated rat aortic rings to sera from patients with septic shock and to sera from dogs made septic by intraperitoneal implantation of infected clots. Isolated rings from rat thoracic aortas were mounted on hooks in chambers filled with modified Krebs' buffer and bubbled with 95% oxygen/5% CO2. After documentation of functional endothelium, the rings were precontracted with norepinephrine. Serum was then added and ring tension measured continuously over the next 20 mins. RESULTS: Sera from normal humans increased ring tension by 6% (60 +/- 39 [SEM] mg tension/mg ring). Sera from nine patients with septic shock decreased tension by 30% (350 +/- 42 mg tension/mg ring; p less than .001). In response to sera from control dogs, tension increased by 16% (122 +/- 37 mg tension/mg ring). In contrast, septic dog sera caused tension to decrease by 36% (278 +/- 38 mg tension/mg ring;p less than .001). Vasodilation was unaffected when the septic patient and dog sera were dialyzed to remove molecules less than 10,000 molecular weight. Chemical deendothelialization with sodium deoxycholate also did not affect the vasodilatory response to septic patient or dog sera. CONCLUSIONS: Septic sera can relax rat aortic smooth muscle. Dialyzing to exclude the effects of small molecules and removing the endothelium did not eliminate this vasodilatory response. These data suggest the presence in septic serum of circulating substances capable of relaxing vascular smooth muscle that may play an important role in the pathogenesis of the cardiovascular abnormalities in septic shock. PMID- 1617995 TI - Reliability of in vivo mixed venous oximetry during experimental hypertriglyceridemia. AB - BACKGROUND AND METHODS: The spectral absorbance of iv lipid emulsion produces interference in the in vitro spectrophotometric measurement of hemoglobin saturation. Therefore, we investigated in vivo mixed venous oximetry during lipid emulsion infusions. Boluses of lipid emulsion, increasing by 0.1-g/kg increments, were infused every 30 mins into nine anesthetized dogs. After each lipid bolus, laboratory and hemodynamic data measurements were repeated, and arterial and mixed venous blood gases were analyzed on a laboratory cooximeter that was equipped for canine blood. The in vivo mixed venous oxygen saturation was continuously monitored via an indwelling, optically equipped pulmonary artery catheter. RESULTS: As expected, increasing concentrations of lipid emulsion increased (r2 = .92) serum triglyceride concentration. As a result, the in vitro measurements of percentage methemoglobin increased artifactually, reducing in vitro measurements of arterial (r2 = .74) and mixed venous (r2 = .44) oxygen saturations. The in vivo mixed venous oxygen saturation, however, remained constant during hypertriglyceridemia (r2 less than .01). CONCLUSIONS: In vivo mixed venous oximetry remained constant during hypertriglyceridemia, while in vitro measurements of arterial and mixed venous saturations were artifactually reduced. PMID- 1617996 TI - Ovarian cancer, Part II: Treatment. AB - The death rate from epithelial ovarian cancer has only slightly decreased in the past decade. In contrast, there have been dramatic improvements in the treatment of germ cell tumors of the ovary and the majority of patients even with advanced disease is now cured because of the development of effective platinum-based combination chemotherapy. Unfortunately, most patients with ovarian cancer have the epithelial histologic type, and only one third of these patients can be cured with standard approaches. It has recently been shown that a subset of patients with early stage ovarian cancer has a greater than 90% cure rate without chemotherapy. Consequently, a major focus of current research is to develop effective screening modalities in order to diagnose epithelial tumors when they are still confined to the ovaries and pelvis. Currently, three fourths of patients are diagnosed at the time the disease has spread throughout the peritoneal cavity, and the standard approach has been cytoreductive surgery followed by combination chemotherapy. The two-drug combination of carboplatin plus cyclophosphamide has now become the treatment of choice, although it is equally effective as and less toxic than a regimen of cisplatin plus cyclophosphamide. In addition, Taxol has been identified as an extremely active agent against this disease, and new Taxol-containing combinations are under clinical investigation. Clinical trials are also in progress with hexamethylmelamine and ifosfamide combinations as well as with more dose-intense regimens based on considerable retrospective evidence that survival is correlated with the dose intensity of platinum compounds. New agents such as WR2721, IL-3, and IL-1 alpha are undergoing clinical evaluation to determine whether the toxicities of platinum compounds can be decreased and lead to further exploitation of the dose response relationship. After induction chemotherapy, approximately 50% of patients will be in a clinical complete remission. Unfortunately, 30% to 50% of these patients will have recurrent disease; clinical trials are currently in progress to determine whether any form of therapy following the initial induction regimen can prevent or delay recurrences. Based on laboratory investigations in relevant models of human ovarian cancer, clinical trials are also in progress with novel new agents that may be capable of reversing drug resistance to platinum compounds and alkylating agents. For patients with germ cell tumors of the ovary, platinum-based combination chemotherapy has produced the same dramatic effects as in testicular cancer. Clinical trials are now focused on retaining therapeutic efficacy but decreasing the toxicity of treatment in these tumors that frequently affect women in their reproductive ages. PMID- 1617997 TI - Oral disposition kinetics of ofloxacin in patients with compensated liver cirrhosis. AB - The disposition kinetics of ofloxacin, a quinolone antibacterial agent excreted essentially unmodified by the kidney, was studied after single oral administration in 8 patients with compensated liver cirrhosis and in 8 control subjects. Mean elimination half-life and apparent volume of distribution were significantly increased in the cirrhotic group (7.6 vs. 4.9 h and 1.6 vs. 1.2 liters kg-1, respectively). A reduction in the renal clearance of ofloxacin was also observed in the cirrhotic patients, in spite of an apparently normal renal function. These observations indicate that also the pharmacokinetics of unmetabolized drugs may be altered in compensated liver cirrhosis. The serum concentration-time profiles of nearly all subjects exhibited a secondary peak 4-6 h after dosing. This double-peak behavior was interpreted as either enterohepatic circulation or biphasic gastric emptying of ofloxacin. PMID- 1617998 TI - Cefonicid versus cefuroxime: an in vitro study of 1,000 Enterobacteriaceae. AB - Cefuroxime and cefonicid, two common representatives of the second-generation cephalosporins, were compared for their spectrum of activity against 1,000 isolates of gram-negative Enterobacteriaceae. Cefuroxime had an overall advantage of 6.3% over cefonicid. Upon investigation, we found that this was mainly due to Escherichia coli: 11.2% of the E. coli strains proved resistant to cefonicid whilst only 0.4% were cefuroxime resistant. PMID- 1617999 TI - Effects of cefuzonam on peptidoglycan cross-linking reactions in gram-negative bacilli. AB - Cefuzonam [CZON, sodium (-)-(6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2- methoxyiminoacetamido]-3-[(1,2,3-thiadiazol-5-yl)thiomethyl]-8-oxo -5-thia-1 azabicyclo(4.2.0)oct-2-ene-2-carboxylate] is a newly developed semisynthetic cephem with a broad antibacterial spectrum. The effects of CZON on peptidoglycan cross-linking reactions were examined in Escherichia coli, Serratia marcescens and Pseudomonas aeruginosa. The cross-linking enzyme(s) from P. aeruginosa was the most susceptible to CZON, although the bacterium was resistant to CZON. CZON was active against S. marcescens in spite of its weak inhibitory activity against the enzyme(s) from the bacterium. PMID- 1618000 TI - Bactericidal activities of ofloxacin and its optically active isomer (DR-3355) on non-growing cells of Escherichia coli and Pseudomonas aeruginosa. AB - In this paper the bactericidal activities of ofloxacin and its optically active derivative, DR-3355, against non-growing cells of Escherichia coli and Pseudomonas aeruginosa are described. E. coli and P. aeruginosa were killed rapidly by ofloxacin and DR-3355. After treatment with these quinolones, the resting cells of E. coli and P. aeruginosa became plasmolyzed, with apparent cytoplasmic shrinkage without filamentation. Membrane-bound intracellular vacuoles and disruption of the cell envelope were also observed, resulting in extrusion of the cytoplasmic contents. These results indicate that non-growing cells of E. coli and P. aeruginosa were susceptible to ofloxacin and DR-3355, as were logarithmically growing cells. PMID- 1618001 TI - Antibacterial activity of cefixime against Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae in the presence of Moraxella (Branhamella) catarrhalis. AB - We measured the sizes of the inhibition zones of oral beta-lactam antibiotics for Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae in the presence of beta-lactamase-producing-Moraxella (Branhamella) catarrhalis by the agar double-layer method. The sizes of the zones of amoxicillin for S. pneumoniae alone were the largest, followed in a descending order by those of cefixime and cefaclor. In the presence of 10(7) CFU/ml of M.(B.) catarrhalis, however, significant reduction of the sizes of the zones was seen with amoxicillin and cefaclor; inhibition with cefixime was nearly unchanged. Similar results were observed in those for S. pyogenes. These variable findings were attributed to the difference in stability of these drugs to the beta-lactamase produced by M.(B.) catarrhalis. When the susceptibility of H. influenzae in the presence of 10(8) CFU/ml of M.(B.) catarrhalis to cefixime, cefoteram, cefpodoxime, cefotiam and cefuroxime was examined, the sizes of the inhibition zones of all the drugs were reduced by the presence of 10(8) CFU/ml of M.(B.) catarrhalis, but those of cefixime were the largest of all the drugs tested. Our agar double-layer method is simple and useful for evaluating the influence of beta-lactamase-producing organism, as M.(B.) catarrhalis, on the disk susceptibility of other pathogens to antibiotics. PMID- 1618002 TI - In vitro activity of a new broad-spectrum, beta-lactamase-stable oral cephalosporin, cefixime, in comparison with other drugs, against Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis and Streptococcus pneumoniae. AB - Cefixime, a new orally absorbed iminomethoxyaminothiazolyl cephalosporin, was tested against some microorganisms involved in upper and lower respiratory tract infections such as Haemophilus (influenzae and parainfluenzae), Moraxella catarrhalis and Streptococcus pneumoniae, isolated in the period from November 1990 to April 1991. Its activity was compared to nine other antimicrobial agents: erythromycin, trimethoprim-sulfamethoxazole, ampicillin, amoxicillin-clavulanate, cefaclor, ceftazidime, ceftriaxone, cefotaxime and ofloxacin. Cefixime inhibits 90% of S. pneumoniae, H. influenzae and H. parainfluenzae, both beta-lactamase producers (BLP) or not (NBLP) at concentrations of less than 0.25 mg/l. It inhibits 90% of M. catarrhalis (BLP and NBLP) at concentrations of less than 1 mg/l. In general, cefixime has a superior in vitro activity with respect to cefaclor and the other cephalosporins as well as erythromycin and amoxicillin (the last one in BLP strains). In the evaluation of the antibacterial activity of beta-lactam against Haemophilus and M. catarrhalis, the authors observed different indications in the guidelines for ampicillin. Cefixime is not destroyed by the plasmid-mediated beta-lactamase produced by Haemophilus sp. and M. catarrhalis (TEM and ROB in Haemophilus strains and BRO in M. catarrhalis). In view of its excellent in vitro activity against the commonly encountered respiratory tract pathogens, cefixime is indicated in the therapy of these infections. PMID- 1618003 TI - Subinhibitory concentration of octenidine and pirtenidine: influence on the lipid and sterol contents of Candida albicans. AB - The effect of subinhibitory concentrations of octenidine and pirtenidine on the lipid and sterol composition of Candida albicans was investigated. The total lipid and sterol contents of C. albicans grown in the presence of either octenidine or pirtenidine were reduced compared with control-grown cells. The major differences in the lipid composition of drug-grown and control cells were phosphatidylglycerol, phosphatidylcholine and monogalactosyldiacylglycerol, which increased in the presence of octenidine and pirtenidine. Lower proportions of phosphatidic acid were found in yeasts grown in the presence of the drugs when compared with control C. albicans. Fatty acid analysis of control-grown cells showed that the major fatty acids were C16 and C18. Drug-grown cells had higher proportions of palmitic and linolenic acids but lower proportion of oleic acid. The C16/C18 ratios were higher for octenidine- and pirtenidine-grown cells than control cells. Differences in the fatty acid composition of major phospholipids and neutral lipids between drug-grown and control yeasts were also observed. Sterol analysis of control-grown cells showed that the major sterol present was ergosterol (65.9%). A significant increase in squalene and 4,14 dimethylzymosterol was observed in pirtenidine-treated cells, while octenidine treated cells showed an increase in zymosterol and obtusifoliol contents. Our results suggest that octenidine and pirtenidine affect the lipids and sterol of C. albicans in different ways. The implications of these findings on the mode of action of these two drugs is discussed. PMID- 1618004 TI - Effects of 1-(halogenalkoxy)alkyl-5-fluorouracil derivatives on cell growth, cell volume and nucleus size of mouse lymphoma cells. AB - The effects of three 1-(halogenalkoxy)alkyl-5-fluorouracil derivatives on cultured mouse lymphoma cells were studied and compared with those of N-methyl bis-(2-chloroethyl)amine hydrochloride (Lost). The derivatives exert only little influence on cell proliferation and cell volume. However, all derivatives cause a concentration-dependent nucleus contraction, probably due to DNA cross-linkings. Bromodesoxyuridine modulates the effects of the derivatives on the DNA, leading to swelling of the nucleus, which may be caused by DNA strandbreaks. It is suggested that the derivatives exert synergistic effects with other factors. It is concluded that these studies are suitable for the prescreening of agents to be investigated in mutagenicity tests. PMID- 1618005 TI - Effect of a membrane-active agent on uptake of adriamycin in Lewis lung carcinoma cells derived from 'primary' and 'metastatic' growths. AB - The treatment of metastatic growth still constitutes a challenge for cancer research. Tumor progression is often accompanied by a loss in sensitivity to previously efficient drugs. Decreased intracellular accumulation of cytotoxic agents is probably the major reason for drug resistance, although other mechanisms have also been described. Properties of the cell membrane have been shown to determine the metastatic phenotype. This cellular organelle is also responsible for the multiple drug resistance phenomenon. Membrane-active agents may increase cell permeability to drugs, counteracting thereby drug resistance. In the present study the effect of the nonionic detergent Tween 80 on sensitivity to adriamycin (ADR) of cells derived from Lewis lung carcinoma 'primary tumors' (PT)-the local growth following subcutaneous inoculation - and 'metastatic tumors' (MT) - lung tumors which develop following intravenous injection - was compared. Flow cytometry analysis demonstrated several differences between cells derived from the PT and the MT: (1) single ADR treatment showed that MT cells possessed a lower percentage of a high ADR permeability subpopulation than PT cells; (2) a dose-dependent shift to a higher ADR accumulating population was seen in the presence of Tween 80 for both cell types. However, the increase in percentage of high ADR permeability cells was more pronounced in MT (up to x4.7) than in PT (up to x1.3) cells. This differential effect of the membrane-acting agent was evident at various ADR (10-50 micrograms) and Tween 80 (0.1-0.4%) concentrations. The present results corroborate previous data obtained in our group in another tumor progression model, AKR lymphoma. PMID- 1618006 TI - Killing rate and growth rate comparison for newer beta-lactamase-stable oral beta lactams against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. AB - A new method of data presentation that takes into account the relationship between growth and killing rate was used to evaluate the comparative in vitro bactericidal activity of cefpodoxime, cefuroxime, cefixime and an amoxicillin/clavulanic acid combination against Streptococcus pneumoniae and beta lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis. For each strain, the viable count decrease (log CFU/ml) after 6 h of exposure to different antibiotic concentrations was plotted against the viable count increase in the control culture, over the same time. Higher killing rates than those predicted by growth rates were defined as a positive balance; lower rates than those predicted by growth rates were defined as a negative balance. The activity of the 4 drugs against S. pneumoniae and M. catarrhalis was characterized by a positive balance. Conversely, the 3 cephalosporins showed a negative balance for H. influenzae. PMID- 1618007 TI - Netilmicin plus ceftriaxone versus amikacin plus ceftriaxone in the treatment of infections in granulocytopenic patients. AB - For the treatment of febrile episodes in granulocytopenic cancer patients, a combination of bactericidal and intravenously administered broad spectrum agents is recommended. An aminoglycoside plus a beta-lactame (piperacillin, azlocillin or IIIrd generation cephalosporins) are the drugs of first choice in an empiric approach. Because of frequent parenteral interventions (e.g. catheters, cannulations) in thrombopenic patients with multifactorial immunosuppression, we consider the application of once daily drugs, such as ceftriaxone, netilmicin or amikacin. For single dose treatment (1st day two applications), we used ceftriaxone in combination with netilmicin or amikacin as the first approach and retrospectively evaluated 47 patients for efficacy and safety. PMID- 1618008 TI - Study on the mechanism of cytogenetic adaptive response induced by low dose radiation. AB - Pre-exposure of human lymphocytes to low dose radiation (D1) could induce a cytogenetic adaptive response expressed as a decrease of chromatid aberrations caused by subsequent large dose radiation (D2). There are two possible explanations for its mechanism, i.e., activation of enzymatic processes by D1 facilitating repair of chromosomal damage and induction of protective proteins by D1 reducing the number of chromosomal aberrations. The results here showed: (1) the cytogenetic adaptive response could be enhanced by hyperthermia (41 degrees C and 43 degrees C) and suppressed by hypothermia (4 degrees C); (2) hyperthermia (41 degrees C) alone could also induce the cytogenetic adaptive response; (3) the cytogenetic adaptive response could be inhibited by cycloheximide--an inhibitor of protein synthesis; (4) supernatant from cultured lymphocytes treated with D1 failed to show the protective effect. The results imply that the cytogenetic adaptive response is not only related to the activation of repair enzymes, but also to the induction of protective proteins. PMID- 1618009 TI - Clinical manifestations and prevalence of different types of supraventricular tachycardia among Chinese. AB - Sixty-nine cases of paroxysmal supraventricular tachycardia (PSVT) were submitted to electrophysiological studies. The prevalence of different types of PSVT is as follows: 49% of the cases had atrioventricular reentry tachycardia (AV-RT), 14.5% atrioventricular nodal reentry tachycardia (AVN-RT), 28% AV + AVN - RT, and 8.5% other types. Altogether 77% in this group had atrioventricular accessory pathway, of which half are concealed pathway. Electrocardiographic characteristics during tachycardia give hints to diagnosis: (1) AV - RT has the fastest heart rate, with 62% 200 BPM or more, and 82% more than 188 BPM; (2) retrograde P waves can be detected in 64% of cases with AV bypass; (3) 50% of AV - RT shows QRS of bundle branch block pattern. Since accessory pathways are present in the majority of PSVT patients in China, the importance of treatment is stressed. PMID- 1618010 TI - Extended parietal cell vagotomy in the treatment of perforation, hemorrhage and stenosis due to duodenal ulcer. AB - Ninety-five patients with perforation, hemorrhage or stenosis due to duodenal ulcer were treated by extended parietal cell vagotomy. Postoperative follow-up ranged from 3.5 to 10 years (mean 6 years) in 88 patients (92%) with acute perforation (60), hemorrhage (8) and stenosis (20). There was no operative mortality. Ulcer recurrence was 2.3%. Only one patient (5%) had restenosis and required reoperation. There was no recurrent hemorrhage and there were few long term complications. According to the Visick classification, 67 patients (76%) belonged to grade I, 13 (14.7%) grade II, 4 (4.5%) grade III, and 4 (4.5%) grade IV. Extended parietal cell vagotomy proved to be safe with excellent results, low ulcer recurrence and few complications. Moreover, recurrent ulcers healed rapidly following medical therapy. The authors believe that extended parietal cell vagotomy should be the treatment of choice for acute perforation, hemorrhage or stenosis due to duodenal ulcer. PMID- 1618011 TI - Automatic perimetry in detecting early glaucomatous visual field defects. A follow-up study. AB - A prospective study was conducted to identify the value of the differential light threshold changes in glaucoma patients. Using Humphrey Field Analyzer, we determined the differential light threshold on 42 preselected points in the Bjerrum area in the age-matched early glaucoma and normal group, each in 50 eyes, whose initial Goldmann perimetries were normal. It was found that both generalized and localized sensitivity of the retina declined obviously in the glaucomatous group. After Goldmann perimetry follow-up for 2.5 years, 24 eyes showed reproducible typical visual field defects (VFD) in the glaucoma group, which appeared in the same location where light threshold had reduced previously. Therefore, a typical glaucoma VFD was preceded by the slight localized depression of light sensitivity in the Bjerrum area. PMID- 1618012 TI - Tube-perilymph fistula. An experimental study. AB - Before exploratory tympanotomy, it is difficult to diagnose an idiopathic perilymph fistula (PLF) because of its variable presentations. An animal model tube-PLF on guinea pigs was established to evaluate the change of the sensitivity of the cochlea function and the value of the postural audiometry in PLF. A fine polyethylene tube (O.D. 0.6mm) was inserted into the scala tympani of the basal turn through the incised round window membrane in 10 experimental guinea pigs, and another 5 as controls. The hearing threshold (HT), action potential (AP) latency for stimulus of 105 dB SPL, difference of HT and AP latency from the test ear down to up were measured by electrocochleography (ECoG) immediately after operation and one week later. The HT, AP latency and postural audiometry showed no significant changes immediately but a significant difference one week later in HT (P less than 0.01) and postural audiometry, the AP latency also presented a significant delay (P less than 0.01). The results showed that the tube-PLF model may be a valuable method for studying chronic PLF. PMID- 1618013 TI - Mirror writing of Chinese characters in children and neurologic patients. AB - Mirror writing was done in 72 preschool children, 40 school children, 60 mentally retarded school children, 40 normal adults, 37 patients suffering from cerebrovascular diseases with or without aphasia and 13 patients with Parkinson's disease. The results showed that total mirror writing was demonstrated in only 2 cases and partial mirror writing with the left hand in 72 cases and with the right hand in 16 cases. The incidence of mirror writing in writing with left hand was higher (45.8%) in preschool children. It gradually decreased to 43.3% in mentally retarded school children, 24.3% in cerebrovascular disease (CVD) patients, 10.0% in school children, 7.7% in Parkinson's disease (PD) patients and 2.5% in normal adults. The relationships between mirror writing and left/right disorientation, between mirror writing and development of Chinese writing language and between mirror writing and higher cerebral function were observed. PMID- 1618014 TI - Ni-Ti memory alloy clamp plate for fracture of short tubular bone. AB - The clamp shape implant has a special memorial function. It consists of one main rod and 3 or 4 pairs of curved short arms located at both sides of the rod. Each pair of arms rolls into a circle, which can embrace 2/3 of the circumference of the fractured bone shaft, thus fixing fragmental bones at multiple points more securely without any limitation to the motion of adjacent joints. Therefore, clamp implant is especially useful for comminuted fracture of the short tubular bone, which is difficult to fix by other methods. PMID- 1618015 TI - Investigation of allotypes of HLA class III (C2, BF and C4) in patients with schizophrenia. AB - The allotypes of HLA Class III (C2, BF and C4) in 60 patients with schizophrenia were investigated. Significantly higher frequencies of BF*F, BF*SO7 and C4A*4 in patients were found as compared with those of the normal controls. The relative risks (RR) of the three allotypes to schizophrenia were 1.81, 7.79 and 4.18 and the etiologic fraction (EF) were 0.086, 0.060 and 0.042, respectively. There were no significant changes of C2 allotypes. PMID- 1618016 TI - Research on rapid identification of auto-microbiology system for pathogenic yeast. AB - The auto-microbiology system yeast biochemical card (AMS-YBC; Vitek System, Inc.) was studied in 77 clinical isolates and 50 laboratory kept isolates on the basis of routine identification. Results of 123 isolates were obtained in 24 hours, while that of the other 4 in 48 hours. 122 (96.1%) were coincidently identified with AMS and routine method. The results suggest that AMS is a rapid, accurate and simple identification method for common pathogenic yeast. PMID- 1618017 TI - Experimental research on antimotion sickness effects of Chinese medicine "pingandan" pills in cats. AB - Pingandan was a secret prescription for treatment of stomach upset, nausea and vomiting for emperors in the Qing Dynasty of China. This study was to compare the effects of Pingandan with those of scopolamine and dramamine on motion sickness (MS) and nystagmus. Fourteen cats were tested in a parallel swing (0.22 Hz, 3.9 m/S2) for 20 min, and then in a rotating chair (10 degrees/S2, 20 rpm) for 1-2 min. The effects of scopolamine 1 mg, dramamine 25 mg and three doses of Pingandan 50x, 30x, 10x of 0.45 g/kg were observed and compared to placebos. These drugs or placebos were administered to each cat 30-60 min prior to the tests. The post-rotary nystagmus and MS symptoms were recorded. The Suri's scale for MS severity, Latin square and double blind techniques were used. The interval between any two tests was 2-5 days. It was found that Pingandan 50x and scopolamine 1 mg were more effective than placebos in reducing MS symptoms (P less than 0.01) and suppressing slow phase velocity of nystagmus (P less than 0.05), while Pingandan 30x significantly reduced MS symptoms only (P less than 0.01). Pingandan 10x and dramamine 25 mg had no anti-MS effect. Chinese medicine Pingandan is an effective anti-MS drug. PMID- 1618018 TI - Treatment of hallux valgus in China. AB - This is a review of the treatment of hallux valgus based on the paper material submitted to the First and Second Sino-American Conferences on Foot Disorders held in Beijing in 1987 and 1990. The data consisted of 676 cases (979 feet) from 10 major hospitals in China. There were 122 men and 554 women, giving a male to female ratio of 1:45. Sixty-nine (10%) cases had a family history of hallux valgus and 120 cases (18%) were associated with hammer toe deformity. The age ranged from 16-85 years with an average of 42. Among the 412 female cases (78.5%) at the age of 20-35, 339 (82.3%) had the history of wearing high heeled and narrow tipped shoes. Osteoarthritis changes of the first M-P joint were seen in 31 cases, all above the age of 60. 615 cases (90.9%) were treated surgically for pain relief and only 25 cases (3.7%) at the age of 20-30 had the deformity corrected for cosmetic purpose. The surgical procedures employed were bunionectomy (Silver's operation, 39 feet), Keller's operation (344 feet), McBride's operation (239 feet) and a variety of osteotomies of the first metatarsal (295 feet). Joplin and Lapidus operations were used by one author in 5 and 2 cases respectively. Overall excellent and good results were obtained in 609 cases (90%) during the follow-up of 1-14 years. PMID- 1618019 TI - Endobronchial leiomyoma. PMID- 1618020 TI - Adenoacanthoma developing in adenomyosis uteri. PMID- 1618021 TI - The fragile X syndrome: isolation of the FMR-1 gene and characterization of the fragile X mutation. AB - Fragile X syndrome, associated with the fragile X chromosome, is the most common cause of familial mental retardation. A breakthrough has been made in molecular biological research into the fragile X site. In this review we describe the molecular investigations that have led to the isolation of the FMR-1 gene. The nature of the fragile X mutation as well as the implications of the DNA test for the mutation are discussed. PMID- 1618022 TI - Molecular analysis of the aberrant replication banding pattern on chromosome 15 in murine T-cell lymphomas. AB - Cytogenetic techniques revealed an altered early replication banding pattern on the distal part of chromosome 15 in some murine T-cell lymphomas. This pattern reverted back to normal replication in somatic cell hybrids that had become non tumorigenic after fusion of leukemic cells with normal fibroblasts. The altered banding pattern was correlated with malignancy. To investigate the molecular basis of the aberrant pattern in more detail, centrifugal elutriation of cells containing bromodeoxyuridine labeled DNA was used to prepare newly replicated DNA from selected intervals of the S-phase from tumor cells, as well as from hybrid cells with the revertant phenotype. These different DNA fractions were probed for DNA sequences distributed over the distal half of chromosome 15. Only two out of ten chromosome 15 specific genes tested showed a clear change in replication timing between the two different cell lines tested. These two genes were the lymphocyte antigen-6, Ly-6, and the neighboring thyroglobulin gene, Tgn, which replicated at the beginning of S in the tumor cells and later in S in the non tumorigenic hybrid cells. PMID- 1618023 TI - Orientation and segregation of a micromanipulated multivalent: familiar principles, divergent outcomes. AB - We studied the orientation and segregation of a particular quadrivalent in living grasshopper spermatocytes. Quadrivalents were detached from the spindle by micromanipulation, then placed and bent as desired. The detached quadrivalents reattach and orient on the spindle. Their orientation is determined by the same principles that apply to ordinary chromosomes in mitosis and meiosis, but the outcome is different. Certain characteristics of the quadrivalent lead to a variety of orientations rather than the single one typical of ordinary chromosomes. Two kinetochores in the quadrivalent are linked to the others by unusually long, flexible chromosome arms. These kinetochores may face either the same pole or opposite poles and tend to orient initially to the pole toward which they face. Consequently, the initial orientation of the flexibly linked kinetochores is variable, and, moreover, they frequently reorient. In contrast, the other two kinetochores are as rigidly connected as those in a small bivalent and so display the typical back-to-back arrangement. Usually, this arrangement leads quickly to a stable orientation of the two kinetochores to opposite poles. Sometimes, however, the back-to-back arrangement changes to a side-by-side arrangement so that the orientation of both kinetochores to the same pole is favored. The combined effect of this diverse behavior is that the quadrivalent has four stable orientations, each leading to a different distribution of chromosomes in anaphase. The result is genetic chaos. Ironically, this chaos is produced by the same mechanisms that, in ordinary bivalents and mitotic chromosomes, produce a single stable orientation and genetically appropriate chromosome distribution. PMID- 1618024 TI - Properties of isolated extrachromosomal nucleoli from Tetrahymena pyriformis. AB - Extrachromosomal nucleoli were isolated from log phase cells of Tetrahymena pyriformis (amicronucleate strain) in a highly purified state. Nucleoli located at the periphery of the macronucleus were detached from the nucleoplasmic mass of isolated macronuclei with agitation and separated from macronuclei by filtration through a Nuclepore membrane filter (pore size 5 microm). The filtrate constitutes the crude nucleolar preparation, as judged by electron microscopy and DNA analysis. Further purification of the nucleoli was performed by isopycnic centrifugation of the filtrate in a Metrizamide density gradient. After this step, the purity of the nucleoli, as defined by rDNA content and measured by analytical CsCl centrifugation, was almost 100%. Electron microscopy of the purified nucleoli revealed structures that resemble those of an in situ nucleoli. Undegraded 35S pre-rRNA, together with 26S and 17S rRNA, could be isolated from purified nucleoli. In vitro RNA synthetic activity was associated with isolated nucleoli. This activity is insensitive to low and high concentrations of alpha amanitin, indicating that the form I RNA polymerase is functioning. PMID- 1618025 TI - Isolation and characterization of a mouse subtelomeric sequence. AB - A mouse subtelomeric sequence, ST1, was generated from genomic DNA of the mouse HR9 (129/Sv origin) cell line by the polymerase chain reaction (PCR) using a single telomeric primer. ST1 was cloned and characterized: it is composed of 670 bp of novel DNA sequence flanked on each end by inverted telomeric hexanucleotide repeats (TTAGGG)n. PCR amplification from BALB/c mouse DNA using this single primer gave the same major product. Southern analysis and PCR using internal ST1 primers confirmed that the ST1 sequence is present in mouse genomic DNA. In situ hybridization to metaphase chromosomes of SJL origin mapped ST1 to many, if not every, mouse telomere. PCR experiments using different combinations of the telomeric, minor satellite, and ST1 primers indicated that some ST1 copies are adjacent to minor satellite sequences, that telomeric and ST1 sequences are not generally interspersed with minor satellite sequences, and that ST1 and the minor satellite have a consistent and specific orientation relative to each other and to the telomere. PMID- 1618026 TI - The genome of the Mediterranean fruitfly Ceratitis capitata: localization of molecular markers by in situ hybridization to salivary gland polytene chromosomes. AB - We hybridized cloned DNA segments to salivary gland polytene chromosomes of the medfly, Ceratitis capitata, and thus established molecular markers for 24 sites on 6 out of 10 autosomal arms. An additional marker identified a medfly repetitive element that hybridizes to approximately 100 autosomal sites as well as a granular network that is thought to represent the X chromosome. Some of the markers correspond to 9 characterized transcription units, while 17 remain anonymous; at least 3 of the latter are restriction fragment length polymorphism (RFLP) markers. The characterized transcription units document that chromosomal arm 5L of C. capitata is homologous to the Drosophila melanogaster X chromosome, in agreement with previous inferences based on the extensive conservation of linkage groups in Diptera. PMID- 1618028 TI - [Relationship between developmental stenosis of cervical spinal canal and spinal cord injury]. AB - A retrospective study of 55 patients with acute cervical spinal cord injury caused by trauma was performed. On radiographic examination of the cervical spine in each of 55 cases showed no fracture or dislocation but developmental stenosis determined on lateral view radiograms. Ninety five point nine percent of this cases had block of the dyeing columns myelographically both in prone and supine positions. Eighty point nine percent of 47 cases demonstrated segmental instability of the cervical spine on full extension and flexion radiograms. Thirty eight cases suffered a minor trauma but resulted in incomplete spinal cord injury with moderate neurologic deficits. Most patients who had been treated conservatively for about 3 years demonstrated the neurologic deficits worsened gradually. In the later 50 cases underwent surgical treatment. A follow-up study showed that Robinson's procedure and laminectomy resulted in unsatisfactory outcome, in contrast to those of open-door technic. It is suggested that developmental stenosis may be a potential factor in the spinal cord injury. PMID- 1618027 TI - Molecular analysis of the lethal(1)B214 region at the base of the X chromosome of Drosophila melanogaster. AB - Approximately 50 kb of genomic DNA was isolated from polytene chromosome bands 19F1 and 2 of Drosophila melanogaster. Bands 19F1 and 2 are in the immediate vicinity of the beta-heterochromatin at the base of the X chromosome and encompass the little fly-like and lethal(1)B214 complementation groups. The cloned DNA consists of an approximately 21 kb stretch of unique or low copy number sequence that is bounded by repetitive elements interspersed with further unique sequences. The presence of repeated sequences is characteristic of regions within and adjacent to beta-heterochromatin. At least part of a tRNA gene cluster is present within the 50 kb of cloned DNA. The cloned region also produces at least 18 discrete size classes of developmentally regulated poly(A)+ RNA species. A 2 kb EcoRI fragment (E10), which lies in the 21 kb stretch of unique sequence, generates seven of these transcripts (of sizes 3.5, 3.35, 2.1, 2.0, 1.5, 1.2 and 1.0 kb) in wild-type flies. However, a small deletion of approximately 75 bp in E10 in a lethal(1)B214 mutant allele is associated with alterations in the production or processing of all seven of these transcripts. These data identify E10 sequences as belonging to the lethal(1)B214 gene and suggest that the wild type lethal(1)B214 gene encodes multiple transcripts. Furthermore, no transcripts of the same size and having the same developmental profile as those generated by the wild-type E10 fragment were identified by probes covering the remainder of the cloned region. This suggests that at least the larger transcripts hybridizing to E10 are partly transcribed from sequences located outside the cloned region, which indicates that the lethal(1)B214 gene extends for more than 20 kb and contains other transcriptionally active sequences within it. PMID- 1618029 TI - [Developmental stenosis of the cervical spinal canal hyperextension injury]. AB - Sixteen cases of cervical spinal cord injury with developmental stenosis of cervical spinal canal were treated. The numbness and quadriplegia of the patients were caused by hyperextension X-ray of the cervical spine showed no fracture or dislocation but the sagittal diameter of the canal and that of the corresponding cervical vertebral body was less than 0.75. All of the patients were treated by operation including laminoplasty on 12 cases. The numbness and quadriplegia in most of the patients were improved obviously after operation. The mechanism of hyperextension injury on the cervical spinal cord was discussed. When spinal column was extended, annulus fibrosus of disk and ligamentum flavum would enfold into the spinal canal and only a slight force would do severe on the cord. Laminoplasty is the recommended treatment for this kind of lesions. PMID- 1618030 TI - [Complications of scoliosis following surgery]. AB - The complications of scoliosis in 100 cases were treated surgically in the past 8 years. The early complications were pulmonary complications (3 cases), syndrome of supra-mesenteric artery (2), and wound infection (3). Late complications were unhooked Harrington instrumentality (10) cases), fracture of Harrington rods (9), protrusion of upper end of Luque rods (7), breakage of tethering wire (4) and pseudarthrosis (3). there was no operative mortality or paraplegia after operation. PMID- 1618031 TI - [Diagnosis and treatment of congenital atlantoaxial dislocation]. AB - 23 patients, aged from 10 to 52 years (24 years on the average), with congenital dislocation of atlanto-axial joint were treated. Symptoms were chiefly functional disturbance of motion; diagnosis was based on malformation of cranio-vertebral junction shown on radiograms; and operation of transoral decompression or/and posterior decompression and fusion was performed on each patient. Such operation did benefited 19 patients, a rate of 82.6%, evaluated in 0.2 to 8.7 years (1.9 years on the average) after operation. Skull traction tried on several patients failed to reduce the dislocation because of dense fibrous tissues in the joint space, hindering reduction. Posterior decompression alone was seldom effective and even dangerous. For this condition, transoral decompression and anterior or posterior fusion is a good choice of treatment. Mechanism of developing symptoms, key points of making diagnosis and surgical procedures were described in detail. PMID- 1618032 TI - [Mechanical efficacy of different internal fixation devices in the treatment of thoracolumbar fractures]. AB - To know the efficacy of different internal fixation devices used in the treatment of thoracolumbar fractures, specimens of 15 adult cadaveric (T-8 to L-4) were prepared and were divided into 5 groups for comparative study. Except the control group, the vertebra of T-12 of every specimen in other 4 groups was artificially fractured, imitating flexion fracture dislocation, with standard technic. Then, they were fixed in each group, with Luque's rod, Dick's screw, pedicle screw plate or Dunn's device respectively. The stress distribution and yielding stress under load and dimensional motions in each group were recorded and compared among the groups and with the control. In the experimental groups, Dunn's device gave the strongest support, against load on the anterior and middle columns. Dick's screw and pedicle screw plate could theoretically fix the anterior, middle and posterior columns rigidly; however, because of the weakness persisted in the connection of their components, their fixation effectiveness was reduced. Luque's rod acted though effectively against bending on every direction, it could not stand much axial load. It is obvious that each of these 4 devices has its own advantages and could be used to prevent horizontal displacement of the fixed fracture, but fail to control torsional stress. PMID- 1618033 TI - [Immunohistocytochemistry in evaluation of spinal cord injury]. AB - The results of spinal cord injury were evaluated immunohistocytochemically with monoclonal antibody to neurofilament (NF) or glial fibrillary acidic protein (GFAP) for labelling the nerve cells, nerve fibres and astrocytes in 13 dogs. Their cords were taken out in 6, 12, 24, 48 hours or 10-12 weeks after trauma by standard injury. Morphometric analysis was also used. We found that the injured nerve fibres expanded gradually and then disappeared, the astrocytes became GFAP positive and the GFAP framework structures disrupted 24 hours after injury. Later in 10-12 weeks after injury, the nerve cells changed in 3 different functional patterns: active phase, stable phase and week phase. There was a significant correlation between axon counting and GFAP area ratio, also the active phase counting to the muscle function. Its biological significance was also discussed. PMID- 1618034 TI - [Surgical treatment of spondylolisthesis]. PMID- 1618035 TI - [Intracerebral cograft of Schwann's cells and fetal adrenal medulla in the treatment of Parkinson's disease]. AB - 10 cases Parkinson's disease received intracerebral cograft of Schwann's cells and fetal adrenal medulla. Good result was achieved. In some cases, symptoms continued to improve after one-year follow-up. There was no "rebounce" phenomenon which was often seen in the autologous adrenal medulla transplantation. We conclude that selection of patients, medication of amamtadion after surgery and cografting of Schwann's cells are essential to the satisfactory results. PMID- 1618036 TI - [Surgical treatment of primary tumor in the right heart]. AB - From April 1986 to March 1990, 5 patients with primary tumor of the right heart were treated surgically at our hospital. Two of them had right atrial myxomas, and one had malignant lymphoma of the right atrium. The remaining 2 patients had tumors of the right ventricle (fibromyxoma 1 patient and leiomyosarcoma 1). The diagnosis was confirmed by 2-D echocardiography in all patients. Three patients with cardiogenic shock were operated on at emergency clinic. There were no operative deaths. Two patients with primary malignant tumors underwent incomplete resection with poor results. Three patients with benign tumors who had the tumors totally removed showed good results after operation. PMID- 1618037 TI - [Long-term results of bioprosthetic valves mounted on flexible stent]. AB - From April, 1984 to April, 1989, 104 heart valve replacements were performed in 103 patients. The atrio-ventricular valves (97 mitral and 7 tricuspid valves) were replace by bioprosthetic valves mounted on the flexible stent made of Elgiloy. They included 91 porcine aortic valves and 13 bovine pericardial valves. Only 74 patients recovered and discharged from the hospital because of high operative mortality of re-replacement and double valve replacement (19 and 30 patients, respectively). These patients were followed-up for 8 to 68 months with a total follow-up period of 297 patient-years. Two patients developed cerebral embolism and two developed bacterial endocarditis. The incidence of the two complications was 0.67%/patient-year. No valve failure occurred. Long-term results of bioprosthetic heart valves mounted on flexible stent were better than those mounted on rigid stent. PMID- 1618038 TI - [Diagnosis and treatment of early rupture of traumatic peripheral false aneurysms]. AB - The causes, symptoms and treatment of ruptured false aneurysms in 14 cases were reviewed with special attention to early diagnosis. Once aneurysmal wall ruptured, emergency surgery was necessary to stop bleeding. The repairment of the artery depended on the position, size of the rupture, and the patient's condition. Small arteries were safely embolized using spring-coil on arteriography. In dealing with ruptured large aneurysm, we suggest resection of the aneurysm and repair of the artery after occlusion of blood circulation by balloon catheter. PMID- 1618039 TI - [Cranioplasty using preserved subaponeurotic bone plate]. AB - Cranial bone defect in 6 patients (5 males and 1 female) was repaired with preserved subaponeurotic bone plate. The defect was caused by evacuation of hematoma (5 patients) and resection of pituitary tumor (1 patient). Bone plates used measured 5-8 x 6-10 cm, and preserved for 57-92 days. Microscopic examination showed that the bone plates was alive, and small blood vessels were connected with two aponeuroses. X-ray examination showed normal density of the bone plates. No complication was noted. The bone plate can be used in postoperative cranioplasty. PMID- 1618040 TI - [Anesthetic management of patients with pre-excitation syndrome]. AB - The authors reviewed the experience of anesthesia in 30 patients under extracorporeal circulation for surgical interruption of Kent's bundle. The key points of anesthetic management are to prevent and control supraventricular tachycardia, which had 35 episodes in 20 of the 30 patients, and disappeared after appropriate treatment. In this group, 18 patients had mild pre-excitation syndrome. After discontinuation of cardiopulmonary bypass, fifteen of the 18 patients were free from pharmacologic support, while 8 of the remaining 12 associated with other cardiac anomalies often necessitated positive inotropic agents. PMID- 1618041 TI - [Reoperation for recurrent gliomas]. AB - Twenty-three cases of recurrent gliomas were reoperated upon. The indications and some factors influencing the length of survival time after reoperation were studied. It was found that reoperation is important in the management of recurrent gliomas, but strict indications must be followed with special attention to prevent CSF leakage, breaking and infection of the incision. Reoperation is not only to prolong life time but also to improve living quality. After reoperation, a comprehensive treatment is needed. PMID- 1618042 TI - [Autohemotransfusion in patients with intraperitoneal hemorrhage. Report of 221 cases]. AB - Autohemotransfusion was performed in 221 patients with intraperitoneal hemorrhage. The total amount of blood autotransfused was 198,760 ml, accounting for 90% of whole the blood transfused during the operations. The average amount of blood transfused was 899 ml per case, the largest amount being 3600 ml. There was no any adverse reaction observed. We consider that autohemotransfusion may avoid some shortcomings of donor's blood, and is of great importance in the treatment of patients with hemorrhagic shock when bank blood is not immediately available. The indications and contraindications of autohemotransfusion are discussed. PMID- 1618043 TI - [Ultrasonic diagnosis of liver hydatid disease]. AB - The experience of the ultrasonic diagnosis of intrahepatic secondary changes in 36 cases with liver hydatidosis was reported. The ultrasonograms were classified into five types: I. separated internal capsule, II. disruptive internal capsule; III. mixed echo; IV. thick-wall calcification; and V. consolidation. We studied the ultrasonogram character of the five types, and considered that the occurrence of type I, type II, and type IV resulted from single cyst pattern, while type III and type V resulted from multiple cyst pattern. Analysing the pathological foundation of the ultrasonogram changes can offer clinicians a reliable basis for choosing a treatment method. PMID- 1618044 TI - [Effect of superoxide dismutase on mitochondrial function in rats with hemorrhagic shock]. AB - We observed the alterations in mitochondrial function and activity of endogenous SOD, and studied the protective effects of SOD on rats with hemorrhagic shock. It was found that after two hours' shock, RCR in hepatic and kidney mitochondria decreased significantly (liver P less than 0.01, kidney P less than 0.05), the activity of endogenous SOD depressed more or less in samples of blood and mitochondrial fraction (blood P less than 0.01. liver P less than 0.01. kidney P greater than 0.05). Further descent was found in these parameters in the deteriorating process of shock. After the rats were treated with SOD, RCR and activity of endogenous SOD increased considerably. Mere reflow did not affect them remarkably. This results suggest that oxygen-derived free radicals be the important factor impairing mitochondrial function in hemorrhagic shock, and that SOD can effectively ameliorate mitochondrial function. PMID- 1618045 TI - [Production and characterization of a group of monoclonal antibodies to human transitional cell carcinoma]. AB - A panel of specific mouse monoclonal antibodies, BIU-H4, BIU-H6, BIU-H9, was obtained by immunization with BIU-87 cells (a transitional cell carcinoma cell line of the bladder), which was blocked by the serum of mouse anti-human lymphocyte. Detailed descriptions were given concerning their reactivity patterns by ABC-ELISA and IIF assays against various cells. They showed positive reactions with transitional cell carcinoma of the bladder and negative with normal bladder. BIU-H6 did not react with any of the other normal or malignant tissues. The subclass of immunoglobulin for BIU-H4,6 was IgG1, for BIU-H9 is IgG2 alpha. The molecular weight of the antigen recognized by BIU-H6,9 is 102 KD. PMID- 1618046 TI - [DNA content examination for atypical hyperplasia of adenosis and carcinoma of the breast]. AB - Nuclear DNA content of breast specimens in 80 cases was measured with microspectrophotometer. The results showed that there was no difference in the nuclear DNA content between normal breast and breast adenosis with epithelial hyperplasia grade I. The DNA content increased gradually with the development of atypical hyperplasia, while there was no difference in DNA content between breast adenosis with atypical hyperplasia grade III, malignant transformation of breast adenosis and breast cancer grade I. There was a statistically significant difference among the other groups. It was extremely important to measure nuclear DNA content in patients with atypical hyperplasia of the breast in order to study the precancerous lesion and to supervise clinically the tendency of cancerous. PMID- 1618047 TI - [Measurement of portosystemic shunting rates during the operation]. AB - Portosystemic shunting rates were measured with Archie's formula in 10 normal dogs and 26 patients with portal hypertension. The average values of the portosystemic shunting rates were 10.1 +/- 4.5(SD) per cent in the 10 dogs and 53.9 +/- 14.2 percent in the 26 patients. There was significantly negative relativity between the difference of the SOPP and FPP and the portosystemic shunting rates (r = -0.885, P less than 0.001). After splenectomy and portoazygous disconnection, the shunting rates were significantly reduced (P less than 0.002 and P less than 0.005, respectively). There was significantly positive relativity between the degrees of patient's esophageal varices and the postoperatively reduced portosystemic shunting rates (r = 0.661, P less than 0.001). It shows that the more the portal blood reverts through the varices, the better the result of portoazygous disconnection. PMID- 1618048 TI - Suppression of myoelectrical activity of gastric smooth muscle by endogenous gastric prostaglandin E2. AB - The myoelectrical activity of the gastric smooth muscle, recorded by a bipolar electrode placed at the gastric antrum in rats, could be recorded when the stomach was distended with 5 ml of physiological saline. This activity may be induced by a mucosal reflex and was inhibited both by atropine and by pirenzepine. Replacement of physiological saline with solutions of NaCl suppressed this myoelectrical activity. This suppression was dependent on the concentrations of NaCl in the solutions, from 0.3 to 1.0 M. Pretreatment with indomethacin (10 mg/kg, intravenous) completely prevented this suppression induced by different concentrations of NaCl solutions. Intragastric administration of 1.0 M NaCl in solution caused an increase in the levels of PGE2 in the gastric lumen. Intragastric administration of OU-1308, a synthetic derivative of PGE1, also suppressed the myoelectrical activity in a dose dependent manner. It is concluded that the suppression of gastric myoelectrical activity by hyperosmolar NaCl may be attributable to the generation of endogenous PGE2 in the stomach. PMID- 1618049 TI - Effect of meal composition and sham feeding on duodenojejunal motility in humans. AB - The disruptive effect of meals of different fat content and caloric value and of sham feeding on the interdigestive migrating motor complex (IDMMC) was studied in eight healthy subjects using an ambulatory recording system that allowed continuous monitoring of small bowel motility for three consecutive days. The durations of fed pattern were not significantly different between meals of 800 kcal/50% fat, 400 kcal/50% fat, and 800 kcal/25% fat, but were significantly longer compared to IDMMC cycle length and sham feeding. The latter two were not significantly different. On a separate day, five subjects consumed a meal of 400 kcal/9% fat and a second one of 800 kcal/50% fat. The duration of the fed pattern following the high fat meal was significantly longer than the low fat one. Sham feeding significantly increased plasma concentrations of gastrin and neurotensin (NT), but did not affect those of cholecystokinin (CCK), insulin, and peptide YY (PYY). The various variables of the IDMMC were not different during the two nights of the study, and velocity of migration of phase III during the first day and both nights was similar. We conclude that the duration of the fed pattern depends, in part, on the composition of the meal. Sham feeding, resulting in an increase in both plasma gastrin and NT concentrations, does not disrupt the IDMMC. When using thin probes, IDMMC is stable during prolonged recording. PMID- 1618050 TI - Ornithine decarboxylase activity during gastric ulcer healing in dogs. AB - Ornithine decarboxylase (ODC) activity has been associated with mucosal growth and injury, yet, little information is available on ODC activity during gastric ulcer healing. We measured ODC activity in the ulcer base submucosa and the surrounding mucosa at 1 cm and 2 cm and assessed ulcer surface healing and a histologic score in experimentally induced ulcers (Quinton ulcer-maker) at 0 and 5 hr and at one, two, three, four, and seven days. A total of 26 dogs were studied, eight of which received 2% difluoromethylornithine (DFMO, a specific inhibitor of ODC) in drinking water. Ulcer healing was assessed by digitizing initial (plug size), and final ulcer surface area and was expressed as percent ulcer surface reduction. A histologic score was assessed by two independent pathologists unaware of the treatment. ODC induction was observed in the submucosa of the ulcer base but not in the surrounding mucosa. The baseline submucosal ODC activity was measured at 0.2 +/- 0.1 pmol (14CO2)/mg protein/hr, and at one day the ODC activity increased to 4.0 +/- 0.7, at three days to 15.2 +/- 5.5, and at seven days to 2.6 +/- 1.0 (P less than 0.001). DFMO treatment delayed GU healing significantly up to three days, but no difference was noted at seven days. The assessed histologic parameters did not correlate with ODC activity, and DFMO treatment did not alter the histologic score. These data suggest that polyamine biosynthesis occurs in the ulcer base submucosa during the first seven days of experimentally placed gastric ulcers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618051 TI - Evidence that gastric antisecretory action of lipopolysaccharide is not due to a toxic effect on gastric parietal cells. AB - We have recently found that bacterial lipopolysaccharide (LPS) or endotoxin at minute doses inhibits the secretion of gastric acid and pepsin in rats. The present study was performed to determine whether this antisecretory action of LPS was a reversible biological response or a result of the destruction of gastric parietal cells by endotoxin. The intraperitoneal injection of LPS into pylorus ligated rats resulted in a dose-related (40-4000 ng/kg) decrease in gastric acid secretion, with maximal inhibition being observed at a dose of 4000 ng/kg. The stomach then was examined both macroscopically and microscopically for the presence or absence of mucosal lesions or damaged gastric parietal cells. No morphological changes in the gastric mucosal structure including parietal cells were observed even in the rats injected with 4000 ng/kg of LPS. Next, basal gastric acid output was compared in the rats that had received LPS (4000 ng/kg, intraperitoneal) or saline alone 24 hr before. There was no significant difference in gastric acid secretion between the saline- and LPS-pretreated groups, indicating that the secretory capacity of gastric parietal cells returned to the control level at 24 hr after the injection of a maximal antisecretory dose of LPS. These results clearly suggest that the LPS-induced inhibition of gastric secretion results not from its toxic or destructive effect on the gastric secretory mechanism but from its reversible biological effect on gastric physiology. PMID- 1618052 TI - Role of prostaglandin E2 in cholinergic-mediated glycoprotein synthesis in canine antrum. AB - We studied the mechanism of cholinergic stimulation of mucin synthesis in canine antral explants, including the role of PGE2 as an intermediate messenger. Isolated antral mucosa was incubated with 10(-5) M carbachol (Cb), 10(-5) M indomethacin (IND), 10(-5) M pirenzepine (PZ), 10(-5) M Cb + 10(-5) M PZ, 10(-5) M Cb + 10(-5) M IND, and 10(-5) M IND + PGE2 (10(-8), 10(-7) and 10(-6) M) in the presence or absence of [3H]glucosamine. After 24 hr, total glycoprotein synthesis was quantitated by Sepharose-4B chromatography and by 10% TCA/1% PTA precipitation with lipid extraction. PGE2 released into the media was measured by radioimmunoassay (RIA). Cb significantly increased total glycoprotein synthesis and produced a significant increase in PGE2 release. The increase in glycoprotein synthesis and the release of PGE2 was blocked by the addition of muscarinic antagonist PZ. The addition of IND significantly inhibited glycoprotein synthesis and almost entirely suppressed PGE2 secretion. IND also inhibited the effect of Cb on glycoprotein synthesis and PGE2 release. Moreover, PGE2 (10(-6) and 10(-7) M) significantly increased the glycoprotein synthesis in the canine stomach. This suggests the coordinate participation of PGE2-releasing cell population in modulation of glycoprotein synthesis in gastric mucosa. PMID- 1618053 TI - Effects of acarbose on starch hydrolysis. Study in healthy subjects, ileostomy patients, and in vitro. AB - The effect of acarbose on hydrolysis of a pure starch meal was investigated in normal subjects and ileostomy patients by means of 13CO2 breath tests and blood glucose levels as parameters of absorption, and of H2 breath tests, serum acetate levels, and ileal loss of carbohydrate as parameters of malabsorption. Additional information on the effect of acarbose on alpha-amylase activity was obtained by in vitro experiments. Acarbose (200 and 400 mg) significantly delayed starch absorption. Serum acetate was found to be a less sensitive marker of malabsorption than breath H2 excretion. After intake of 50 g starch plus 400 mg acarbose, 23-71% of the starch load was lost in the ileostomy effluent, for a large part as starch. This suggests that acarbose considerably inhibits alpha amylase, and not only brush-border enzymes. In vitro experiments confirm that an inhibition of two thirds of alpha-amylase activity can be expected from pharmacologically used doses of acarbose. PMID- 1618054 TI - Long-term outcome of severe radiation enteritis treated by total parenteral nutrition. AB - The outcome of 31 patients with severe radiation enteritis treated by total parenteral nutrition (TPN) was analyzed. Before initiation of parenteral nutrition, 18 of the patients had not had abdominal surgery, while 13 had either a resection or an intestinal bypass for radiation enteritis. Median follow-up was 2 1/2 years (range: 1 month to 12 years) from the time of initiation of parenteral nutrition. Surgery was required in 15 cases because parenteral alimentation could not be continued. Only eight of these 15 were able to resume a normal oral intake. Total parenteral nutrition allowed oral feeding to be resumed in 11 (36%) after a median follow-up of 40 months (range: 6-142 months). In general, total parenteral nutrition was well tolerated and was associated with low morbidity. Eighteen patients died, 13 of complications due to radiation therapy, four of cancer recurrence, and one of an unrelated cause. Survival probability was 58% at one year and 36% at five years. When possible, prognostic factors present either before or at initiation of total parenteral nutrition were analyzed. Age, predisposing vascular factors (hypertension, diabetes mellitus, or vascular disease), and enteric fistula and/or perforation were found to have prognostic value. The probability of clinical radiation enteritis recurrence was 34% at one year and 47% at two years. A clinical recurrence of symptoms was more frequent but not significantly so after parenteral nutrition as compared to surgical therapy of radiation enteritis. Although TPN corrected denutrition and allowed deferred surgery in some patients, severe radiation enteritis remains a poorly predictable progressive disease with numerous relapses. PMID- 1618055 TI - Spatial clustering of simultaneous nonhereditary gastrointestinal angiodysplasia. Small but significant correlation between nonhereditary colonic and upper gastrointestinal angiodysplasia. AB - Simultaneous nonhereditary colonic and upper gastrointestinal angiodysplasia were spatially clustered in an endoscopic study of 46 consecutive patients. For example, clustering of colonic angiodysplasia was demonstrated using a nonparametric test of clustering (Kruskal-Wallis statistic with 29 degrees of freedom = 76.2, P less than 0.0005), and a parametric test of clustering (F test statistic with 29 and 101 degrees of freedom = 6.91, P less than 0.0005). In accord with spatial clustering, only two of 13 patients (15%) with colonic angiodysplasia who underwent panendoscopy had upper gastrointestinal angiodysplasia. Two of nine patients (22%) with upper gastrointestinal angiodysplasia who underwent colonoscopy had colonic angiodysplasia. These findings suggest that local factors may be important in the pathogenesis of simultaneous nonhereditary angiodysplasia. Possible local factors include intermittent venous obstruction, increased intraluminal pressure, intermittent abnormal arterial flow, and local vascular degeneration. Due to the approximately 20% correlation between upper and lower nonhereditary gastrointestinal angiodysplasia, the upper and lower tract should be examined by endoscopy prior to elective local resection for bleeding from gastrointestinal angiodysplasia. PMID- 1618056 TI - Regional alterations in intestinal sucrase expression in streptozocin-treated chronically diabetic rats. AB - In ad libitum-fed diabetic rats, sucrase specific activities in jejunum and ileum were significantly increased two- to threefold compared to controls, a response unaltered by pair-feeding. Gradients of sucrase activities along the ileal villus to-crypt axis were readily measured in crypt regions in diabetic, but not in nondiabetic, rats. Changes in sucrase activities were commensurate with increases in sucrase immunoreactivity and not a result of altered functional activity. Insulin treatment reversed these effects, although insulin-deficiency, studied in food-deprived, nondiabetic rats, did not affect sucrase expression. We conclude that chronic diabetes significantly stimulates sucrase expression along the proximal-to-distal and villus-to-crypt axes of rat small intestine. In ileum, these changes suggest marked alterations in phenotypic development of enterocytes along the villus-to-crypt axis. Alterations in sucrase expression do not appear to correlate with insulin states and are not a consequence of altered functional activity. PMID- 1618057 TI - Effects of prolonged exposure to histamine on guinea pig intestinal neurons. AB - Intracellular microelectrodes were used to study the effects of prolonged exposure to histamine on the electrophysiological behavior of AH/type-2 neurons in the myenteric plexus of the guinea pig small intestine. Application of histamine activated H2 receptors to convert the neurons to a heightened state of excitability. Heightened excitability was evident as repetitive spike discharge made possible, in part, by suppression of postspike after-hyperpolarization. The hyperexcitable state persisted unchanged for prolonged periods of 4.5 hr in the continued presence of histamine, suggesting that desensitization may never occur in vivo. The results are interpreted as a neural correlate for the pathophysiology associated with microscopic colitis and other inflammatory conditions involving mast cell hyperplasia. PMID- 1618058 TI - Ultrastructural study of M cells from colonic lymphoid nodules obtained by colonoscopic biopsy. AB - The present study was undertaken to investigate ultrastructurally the epithelium covering lymphoid nodules obtained from colonoscopic biopsies of the human colon and rectum. Colonoscopy using the dye spraying contrast method was performed in nine patients who showed x-ray evidence of lymphonodular hyperplasia. Fifty-two colonoscopical biopsy specimens of lymphoid nodules were obtained from the ascending, transverse, and descending colon and rectosigmoid region. All specimens were observed by light and electron microscopy. Light microscopy disclosed large lymphoid follicles protruding into the lumen with a "dome-type" configuration. These extended to the lamina propria of the mucosa and were associated with a massive lymphoid aggregation extending as far as the muscularis mucosa from the submucosa. The epithelium covering these nodules contained a few goblet cells and many lymphocytes. Observation of the elevated surface at the apex by scanning electron microscopy revealed M cells with sparse microvilli in the dome epithelium surrounded by crypts. Transmission electron microscopy disclosed M cells enfolding many immature or mature lymphocytes and plasmocytes. The M cells had cytoplasmic microvilli (so-called "microfolds") on their surfaces, well-developed tubulovesicular systems, and vacuoles in the cytoplasm. The basic structure of the M cells as observed by scanning and transmission electron microscopy was the same as that of M cells in the Peyer's patches of humans and mice. The apical surface of the colonic lymphoid follicles in Crohn's disease patients was associated with erosions observed by scanning electron microscopy. The erosions proved to be the naked surface of the dome after removal of the epithelium, and many holes from 2.0 to 6.0 microns in diameter were observed on the naked surface. At high magnification, lymphocytes were seen projecting from holes (18%) on the naked surface of the dome. These ultrastructural findings indicate that human colonic lymphoid follicles are very similar to those seen in other species. PMID- 1618059 TI - Effect of gut-associated lymphoid tissue on cellular proliferation in proximal and distal colon of the rat. AB - In previous studies, chemically induced colonic carcinomas were found to originate preferentially from crypts adjacent to lymphoid tissue. Proliferative parameters and mucosecretion were analyzed in proximal and distal rat colon in relation to the proximity of lymphoid patches. Animals received an intraperitoneal pulse of bromodeoxyuridine 1-hr before death. In both proximal and distal colon, crypts located at the immediate proximity of the lymphoid formations contained fewer mucous cells (P less than 0.001), but a higher percentage of proliferative epithelial cells (P less than 0.001) than the crypts far from lymphoid formations. The labeling index was higher in crypts adjacent to lymphoid patches compared to crypts distant from lymphoid patches only in the lower third of the crypts. The association of an increased proliferative activity and a decrease in differentiated mucosecreting cells in colonic crypts adjacent to lymphoid patches could be related to the particular sensitivity of these crypts cells to the effects of mutagens and carcinogens. PMID- 1618060 TI - Malignant lymphoma of the liver. Report of five cases and review of the literature. AB - Primary hepatic lymphoma is a rare disease. We report five cases here and summarize clinical and pathologic features of our own and reported cases from Western countries and Japan. The total number of cases was 68. The age of patients ranged from 7 to 87 years (median 55) with a male-to-female ratio of 3.1:1. Chronic hepatitis or cirrhosis before onset of hepatic lymphoma was noted in 44% of Japanese cases and 9.6% of Western cases. Macroscopically, the liver was occupied by solitary mass (60%), multiple masses (35%), or a diffuse lesion without nodule formation (5%). Histologically all cases were non-Hodgkin's lymphoma with the diffuse large cell type being most common. Three cases (4.4%) were follicular lymphoma. Immunohistochemically about 80% of the cases were B cell type. Follow-up study showed that hepatic lymphoma had a relatively favorable prognosis when early detection of the disease was possible. PMID- 1618061 TI - Serum markers of immune activation and liver allograft rejection. AB - We monitored the immune response after liver transplantation in 20 patients by measuring the serum levels of soluble interleukin-2 receptor (sIL-2R), soluble CD8 (sCD8), serum amyloid-A protein (SAA), and tumor necrosis factor-alpha (TNF alpha). In six patients data were available to extend the follow-up period to one year. In all patients mean sIL-2R levels increased in the first month after liver transplantation, and subsequently decreased to values similar to pre-OLT ones, while SAA mean levels rose in the first week after OLT only in patients with rejection. sCD8 levels did not significantly rise after OLT, and TNF-alpha was undetectable in most cases. During episodes of rejection, rejector patients had significantly higher levels of sIL-2R, sCD8, and SAA than stable (without complications) patients. Conversely, no significant difference between rejectors and patients with other complications existed for any of the markers studied. These results diminish the importance of these serum markers of immune activation as laboratory tools in the differential diagnosis of acute rejection from other complications. However, sIL-2R, SAA, and sCD8 levels correlated with the histological grade of rejection and therefore can be utilized to monitor patients with an established diagnosis of acute rejection. PMID- 1618062 TI - Granulomatous tonsillitis. A rare extraintestinal manifestation of Crohn's disease. AB - Oral lesions, varying in nature and location, appear to be one of the common extraintestinal manifestation of Crohn's disease. In particular, oral involvement preceding intestinal disease may lead to the diagnosis of Crohn's disease. The present case report of a 17-year-old male patient describes a very rare nonintestinal manifestation of Crohn's disease with severe granulomatous involvement of the tonsils. A sore throat caused by hyperplastic tonsils with granulomatous inflammation as an oral manifestation of Crohn's disease was the leading symptom in this case. PMID- 1618063 TI - Reversal of gastric electrical dysrhythmias by cisapride in children with functional dyspepsia. Report of three cases. AB - Three children (ages 5, 7.6, and 8 years), with recurrent unexplained upper abdominal symptoms such as vomiting, epigastric pain, anorexia, early satiety and without structural or mucosal abnormalities of gastrointestinal tract, underwent electrogastrography (EGG)--recording of gastric electrical activity using cutaneous electrodes positioned on the epigastric region and connected to a recording polygraph. Frequency of EGG signals was analyzed by fast Fourier transform. Significant changes of fasting and fed gastric myoelectrical activity (tachygastria, bradygastria, flatline pattern) were recorded in the three patients; furthermore, gastric emptying (GE) of a solid-liquid mixed meal, measured by ultrasonography, was significantly prolonged in them. A follow-up study was carried out after an eight-week course with oral cisapride: in all patients symptoms improved, GE time normalized, and EGG analysis showed normal electrical rhythm. It is suggested that gastric dysrhythmias can play a pathogenetic role in patients with functional gastrointestinal symptoms and that symptomatic improvement is accompanied by normalization of gastric electrical rhythm. PMID- 1618064 TI - Tuberculous abscess of the pancreas. Case report and review of the literature. PMID- 1618065 TI - Muscle cramps in chronic liver diseases and treatment with antispastic agent (eperisone hydrochloride) PMID- 1618066 TI - Creatine kinase isoenzymes in diagnosis of intestinal infarction. PMID- 1618067 TI - Diffuse esophageal spasm. PMID- 1618068 TI - Ischemic colitis associated with psychotropic drugs. PMID- 1618069 TI - Computer assessment of life-style in a gastroenterology clinic. AB - To examine the potential benefit of a computer-assisted interview about life style in gastroenterology practice, 34 consecutive patients attending a gastroenterology clinic were questioned by a computer using software designed to obtain a comprehensive history of alcohol, caffeine, cigarette, and illicit drug use, together with an assessment of exercise, sexual activity, and nutrition. Comparisons of the information obtained by the computer with clinical records revealed that physicians documented only 3% of the patients as problem drinkers, 3% as caffeine abusers, and 17% as smokers, whereas the computer identified 10% of the patients as problem drinkers, 27% as caffeine abusers, and 43% as smokers. These findings imply that patients may be more apt to tell more about adverse life-style to the computer than to a physician during clinical interview. In a sample patient population from a gastroenterology clinic, a microcomputer provides an acceptable, efficient, and potentially cost-effective way to assess life-style. PMID- 1618071 TI - Chylothorax: a complication of thoracic trauma or surgery. AB - Chylothorax is a troublesome complication of thoracic trauma and surgery. The critical care nurse's assessment of respiratory changes is frequently the first sign that this serious complication is occurring. Chylothorax may cause a previously stable thoracic patient to develop sudden, potentially serious respiratory problems. PMID- 1618070 TI - Cisapride vs metoclopramide. An acute study in diabetic gastroparesis. AB - Radionuclide gastric solid-phase emptying was studied in 10 subjects with diabetic gastroparesis comparing the acute intravenous administration of cisapride (2.5, 5, 10 mg), placebo, and metoclopramide (10 mg). No hemodynamic or electrocardiographic changes were noted. While both cisapride and metoclopramide normalized impaired solid emptying, cisapride at its highest dosage (10 mg) resulted in significantly faster gastric emptying (P = 0.003) than metoclopramide. The effects of cisapride were dose related and correlated well (r = 0.48, P less than 0.01) with the plasma drug levels. Clinical studies of chronic oral usage must take into account the dose-related response and factors affecting blood levels. PMID- 1618072 TI - Temporary DDD pacing: evaluating hemodynamic performance. AB - Temporary DDD pacing is new technology which requires careful nursing assessment and monitoring of the patient. Although nursing care for temporary DDD pacing patients is similar to permanent DDD pacing, there are some unique aspects related to the temporary nature of this treatment. PMID- 1618073 TI - The clinical nurse specialist role in product research and development. AB - Think about the variety of products used each day in the critical care environment. They include everything from the most sophisticated monitors to the many disposable products. Most products function very well, but when they do not, do you wish you could talk to the person who designed that product? How can your input make medical products work better? The authors describe a career opportunity open to critical care nurses, that of a clinical nurse specialist for a medical products corporation, whose job it is to influence the design and quality of medical products. PMID- 1618074 TI - Physician collaboration dilemma. AB - This dilemma which was submitted to DCCN for review involves a collaboration problem between two physicians, the family, and a nurse with both legal and ethical implications. Following the case is a legal and an ethical analysis by DCCN consultants in these fields. This case is from a Neonatal Intensive Care Unit (NICU) setting, but these conflicts between medical departments occur in all critical care settings, so the key legal and ethical issues are applicable in all ICU settings. PMID- 1618075 TI - Copel and Stolarik's research analysis on SvO2 monitoring. PMID- 1618076 TI - [In vitro quantitative study on invasive process of two human nasopharyngeal carcinoma cell lines, CNE-1 and CNE-2Z]. AB - Computer-image processing system was used in the quantitative study on invasion in organ culture of two human nasopharyngeal carcinoma cell lines of different degree of differentiation, CNE-1 and CNE-2Z. For invasion of tumor cells into precultured heart fragments (PHF), observations were done on days 1,3,5 and 7 after organ culture. The results showed that the invasion of both CNE-1 and CNE 2Z cells was progressive. The invasion of CNE-1 tumor cells covered 82.22% of PHF on day 7, but on days 1 to 3 the invasion of CNE-2Z tumor cells covered 80-92% of PHF. This indicates that CNE-2Z cells are more invasive then CNE-1 cells. PMID- 1618077 TI - [Preparation of an anti-human immunotoxin against bladder carcinoma and its in vitro targeting cytotoxicity]. AB - The intact ricin was linked to a monoclonal antibody BD I-1, which recognizes a determinant expressed on two human bladder carcinoma cell lines, BIU-87 and E-J, to form an immunotoxin BD I-1 Ricin. The results of indirect immunofluorescence test, FACS analysis and competition binding assay showed that the binding activity of antibody in this immunotoxin was retained by 80% of the original activity. The in vitro cytotoxicity assay indicated that the immunotoxin in the presence of 0.1 mol/L galactose is potent cytotoxic agent for BIU-87 and E-J cell lines. The immunotoxin BD 1-1-Ricin could kill the target cells BIU-87 and E-J cell lines by 50% at a concentration of 0.00008 mumoI/L and 0.00025 mumol/L respectively. At a concentration of 0.001 mumol/L no apparent cytotoxic activity to human colon carcinoma Lovo cell line was observed. PMID- 1618078 TI - [Comparative study of single-point method and multipoint method in the measurement of estrogen receptor and progesterone receptor in breast cancer]. AB - A comparative study of estrogen receptor (ER) and progesterone receptor (PgR) by single-point method and multi-point method in dextran coated charcoal assay (DCC) was carried out in 50 and 47 cases of breast cancer, respectively. Taking 10 fmol/mg protein as the positive value, the conformation rate of both methods in ER measurement was 96.0% (48/50) with r = 0.978 by linear regression analysis (P less than 0.001). In PgR measurement, the conformation rate of both methods was 95.7% with r = 0.988 (P less than 0.001). Statistically, the difference between single-point method and multi-point method in the ER and PgR measurements was not significant (P greater than 0.5) both in rank-sum test and in paired t-test. The authors suggest that ER and PgR of breast cancer samples be measured with single point method for its simplicity and less tumor tissue required. PMID- 1618079 TI - [Estimation of cancer latency using data from a case-control study with time related factors--estimated latency for consumption of alcohol and tobacco in relation to gastric cancer]. AB - As a practical application of theory, the susceptible exposure age and latency distribution of consumption of alcohol and tobacco in relation to stomach cancer is discussed. It was revealed that, in univariate, estimation of the susceptible exposure age of alcohol and tobacco were 15-50 years and 35-50 years. The estimated latency were 35 years and 15 years. Those of accumulative period and preneoplastic period were 30 and 10 years. In a multivariate analysis, the latency for alcohol consumption was changed to 20 years as the incubation time in preneoplastic period was prolonged by 5 years due to consumption of vegetables. This could give a theoretical interpretation of second line cancer prevention. PMID- 1618080 TI - [Surgical treatment for carcinoma of gastric stump--a report on 13 patients]. AB - Thirteen patients with carcinoma of gastric cardia after gastrectomy were treated in our hospital from 1981 to 1990. They comprised 1.3% of 932 cancers of the gastric cardia treated during the same interval. Partial esophagogastrectomy and esophagogastrectomy were performed under the aortic arch in 2 patients. Total gastrectomy was carried out in 8 patients with 7 Roux-Y and 1 end-to-side esophagojejunostomy. In the remaining 3 patients, only exploration was done. In the resected patients, two (20%) were complicated by anastomotic leak which was obviously higher than that by the conventional partial esophagogastrectomy for gastric cardia carcinoma. Due to reflux of bile and pancreatic juice, the incidence of gastric cardiac cancer in gastric stump after Billroth II operation was much higher than that following Billroth I type. Hence, Billroth I type should be the method of choice for patients to be operated by the distal partial gastrectomy. If Billroth I type was not feasible, Roux-Y anastomosis should be the alternative for Billroth II type in order to reduce the possibility of developing cancer in the proximal pouch. The route of entry, either left posterolateral thoracotomy or left thoracoabdominal incision should be resorted to in conformity with the size of the tumor. PMID- 1618081 TI - [Association of esophageal carcinoma with achalasia--report on 7 cases]. AB - Among 11,821 cases of esophageal carcinoma treated in a 32 year period, 7 were found to be associated with achalasia (0.059%). Five cases were proved by biopsy or cytology and 2 were diagnosed by esophagograms. There were 4 men and 3 women. The age ranged from 30-54 years with a median of 38. The age was younger than that of esophageal carcinoma unassociated with achalasia. Duration of achalasia was from 7 to 20 years. Three patients died within 1 year and 1 died 17 months after diagnosis. Three were lost to follow-up. The presenting symptoms were aggravating dysphagia in 4; and hoarseness, dyspnea and bloody regurgitation in the other two. Patients with achalasia should be treated energetically in the early stage. Double contrast esophagography and esophagoscopy should be done carefully during the followup. Preparation of the esophagus is most important when performing the X-ray examination of the esophagus. PMID- 1618082 TI - [Pathologic and immunohistochemical study of 11 patients with malignant lymphoma of the gonad]. AB - We report 11 cases of malignant lymphoma of the gonad collected during the past 31 years in our hospital. 8/11 cases conformed well to Fox's criteria for primary gonadal malignant lymphoma. Clinically, they often manifest as a mass in the gonad without any symptoms. Histologically, diffuse NHL of intermediate or high malignancy was observed. According to morphologic criteria of the working formulation in combination with the immunohistochemical study, five cases were designated as T-cell lymphoma. This frequency in Chinese is different from that reported in the western countries. PMID- 1618083 TI - [Long-term results of radiotherapy for malignant tumors of the nasal cavity- report on 317 patients]. AB - From 1964 to 1982, 317 patients with malignant tumors of the nasal cavity were treated by radiotherapy. All had been proved pathologically prior to treatment. The over-all 5- and 10-year survival rates were 42.6% and 32.7%. Those of T1N0 lesions were 64.3% and 54.3%. Patients with submaxillary metastasis gave 5- and 10-year survivals of 35.3% and 26.9% while those with regional lymph node metastasis in the neck gave 26.9% and 15.8%, respectively. The results of orthovoltage X-rays treatment were not inferior to those of telecobalt. Pathologic classification and the radiation dose given bore no weight on survival. The major sequelae were nose bleeding (due to mucosal atrophy), deformity, atrophy or perforation of septum. 57.1% of death was attributed to local progression or recurrence while 32.5% due to distant metastasis. 72% of death occurred within 2 years of treatment. PMID- 1618084 TI - [Color Doppler flow imaging and duplex Doppler in the examination of primary liver cancer]. AB - We examined 40 cases of primary liver cancer with color doppler flow imaging and duplex doppler. In 20 cases, there was arterial flow in the tumor. In 17 cases, there was arterial and portal venous flow in the tumor. In 22 cases, there was arterial flow entering the tumor from its surroundings. In 28 cases, the right or left hepatic artery was dilated. We compared the results of digital subtraction angiography with the doppler ultrasound in 28 cases and found the difference was not significant (chi 2 = 1.05, P greater than 0.05). Therefore, we believe that the doppler ultrasonography is the method of choice in the diagnosis of primary liver cancer. PMID- 1618085 TI - [Experimental and clinical studies on pancreatic duct obstruction in preventing pancreatic fistula formation]. AB - Even after prolonged use in clinical practice, obstruction of the pancreatic duct in preventing fistula formation still lacks solid proof. Sixteen dogs were randomized into an pancreatic duct obstruction group and a control group. Four to 8 ml of silicon gel was injected into the pancreatic duct in the former group while the latter group received exploratory laparotomy only. The pancreas was examined histopathologically 1, 3, 5, 7 and 9 months after operation. It was shown that the exocrine glands underwent marked atrophy but the endocrine glands showed only mild damage. Clinical studies on 27 patients who were operated for pancreatic cancers and diseases showed that pancreatic fistula developed in 7.7% of patients (1/13) in the obstruction group and 21% (3/14) in the control group. PMID- 1618086 TI - [Relationship between plasma and urinary platinum pharmacokinetics with cisplatin nephrotoxicity in breast cancer patients]. AB - In 25 cycles of 20 breast cancer patients who received 26 cycles of high-dose cisplatin (100 mg/m2, iv drip), the urinary Alb, IgG and NAG values were elevated above normal. These patients were divided into low-nephrotoxicity and high nephrotoxicity groups by the degree of renal dysfunction. Of these patients 35% showed high-nephrotoxicity. They had significantly higher plasma and/or urinary Pt peak levels during cisplatin infusion than did those with low-nephrotoxicity. And 70-80% of the patients developed significant nephrotoxicity when the urinary Pt level rose up to greater than 40 micrograms/ml or plasma Pt level greater than 4 micrograms/ml. It is very important to keep the urinary and plasma Pt level below 40 micrograms/ml and 4 micrograms/ml respectively in order to reduce the nephrotoxicity. It is suggested that the urine output be maintained over 300 ml/hr for 2 hours before and after the completion of infusion and greater than 100 ml/hr in the following 3 days. This helps keep the cisplatin-induced nephrotoxicity in less severe and the function of kidney easy to recover. PMID- 1618087 TI - [Relationship between gastric carcinoma and enzyme spectrum activity in gastric mucosal intestinal metaplasia]. AB - Biochemical method was adopted to examine 10 kinds of histologic enzyme spectrum activities in gastric intestinal metaplasia, carcinoma and normal or superficial gastritis mucosa taken from different sites from 17 fresh surgical specimens of stomach. The enzymes are aldolase (ALD), pyruvate kinase (PYK), phospho hexo isomerase (PHI), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), hydroxybutyrate dehydrogenase (HBD), glutamic-pyruvic transaminase (GPT), alkaline phosphatase (AKP), acid phosphatase (ACP), r-glutamyl-transpeptidase (gamma-GT). Among glycolytic enzymes the content of ALD, PYK in intestinal metaplasia were 24.5 u and 24.6 u respectively, which were higher than those in the normal mucosa (15.7, 18.0) and lower than carcinoma (28.4, 29.6) (P less than 0.01-0.05). The content of CPK in intestinal metaplasia was lower (218.5 u) than that in the normal (463.9 u) and higher than that in carcinoma (110.3 u) (P less than 0.01). Among protease and amino acid enzymes the content of HBD in intestinal metaplasia was lower (108.2 u) than those in the normal (221.3 u) and carcinoma (113.9 u) (P less than 0.05). The content of GPT in intestinal metaplasia was (6.7 u) which was lower than that in the normal (9.4 u) and higher than that in carcinoma (3.7 u) (P less than 0.01). The above results could provide reference indices for judging the potential malignancy of gastric intestinal metaplasia. PMID- 1618088 TI - [Characteristics and reactivities of a panel of monoclonal antibodies (McAbs) recognizing human colon cancer associated antigens]. AB - Characteristics and reactivities of 16 monoclonal antibodies (McAbs) were identified. They were prepared from mice immunized with freshly isolated colon carcinoma cells. Of these 16 McAbs, 13 belonged to IgG1, and 3 to IgM. The reactivities by immunohistochemical staining revealed 2 varieties: tumor associated antigens and common normal tissue antigens as defined by McAbs with 737 kinds of tissues and cells from more than 12,000 samples. The antigens defined by McAbs were assayed by western immunoblotting to have a about molecular weights of 200 KD as glycoproteins unrelated to CEA. These results suggest that these McAbs may be used for further research on cancers. PMID- 1618089 TI - [Preliminary study on nutrition and precancerous lesions of the esophagus in the adolescents]. AB - This paper reports the prevalence of chronic esophagitis and nutritional status among 538 persons 15-26 years old in the high-risk area of esophageal cancer. 166 subjects were from households with history of esophageal cancer while 372 from households without. The frequency of chronic esophagitis among male and female adolescents in the high risk areas (37.6% and 36%) was significantly, higher than that in the low risk areas. Furthermore, the frequency of chronic esophagitis in the adolescents in households with history of esophageal cancer was also higher than that without history of this cancer. There was a positive correlation between avitaminosis C and chronic esophagitis. Suffering from avitaminosis C and B2, these people are prone to develop chronic esophagitis which, in turn, may serve as an early phase in the carcinogenesis of esophageal epithelium. PMID- 1618090 TI - [Cytomorphometric analysis of normal, premalignant and malignant nasopharyngeal epithelium]. AB - Cellular morphology of nasopharyngeal epithelium in 76 specimens was quantitatively analyzed by stereological technique using point-counting method. There were 18 normal epithelium, 16 simple hyperplasia and metaplasia, 18 dysplasia and 24 untreated nasopharyngeal carcinoma (NPC). Altogether 19 parameters were morphometrically measured and calculated. The results showed that with the process of malignant transformation the great majority of cellular parameters gradually changed. There was no marked difference between the normal and simple hyperplastic and metaplastic epithelium. The majority of parameters of dysplastic cells were significantly different as compared with the other three groups. It is highly suggestive that the transitional nature of dysplasia from the normal to the malignant cells shows no significant difference concerning these three parameters in terms of mean cellular area (MCA), the standard deviation of nuclear area (SDNA) and surface area per unit volume of nucleus (SsV). However, it is valuable to analyze these three parameters in discriminating the precancerous lesions. Six of the 19 parameters processed by multivariate stepwise analysis were useful in discriminary functions. The 76 specimens as re-estimated by these 6 functions gave a conformation rate of 91% to the clinicopathologic diagnosis. Cytomorphometric analysis might be of predictive value in the diagnosis of early malignant change in the nasopharyngeal epithelium. PMID- 1618091 TI - [Structure of qualifications for the nursing professions. Place of the nursing professions in the educational system of the Federal Republic of Germany]. PMID- 1618092 TI - [Structure and organization of the educational system in nursing]. PMID- 1618093 TI - [Continuing education--a necessity]. PMID- 1618094 TI - [Taking stock of nursing personnel in Germany]. PMID- 1618095 TI - [From head nurse to nursing administrator]. PMID- 1618096 TI - [Public health and nursing]. PMID- 1618097 TI - [The academization of nursing]. PMID- 1618098 TI - [The importance of nursing research for nursing]. PMID- 1618099 TI - [Boards for the nursing professions]. PMID- 1618100 TI - [Alternatives to Nursing Boards]. PMID- 1618101 TI - [Possibilities and limitations of a nursing department. Nursing and politics]. PMID- 1618102 TI - [Nursing unions--the perspective of the future]. PMID- 1618103 TI - [Quality circles in geriatric and general nursing. A participative effort for the organizational and personal development in health facilities]. PMID- 1618104 TI - [Geriatric nursing. Concepts, limits and perspectives of geriatric nursing as a profession]. PMID- 1618105 TI - [Pediatric nursing between professionalization and women's socialization]. PMID- 1618106 TI - [Requirements for instruments for cleaning and disinfection of flexible endoscopes]. PMID- 1618107 TI - [Nursing problems in the prevention of thrombosis]. PMID- 1618108 TI - [Compression stockings: caring for a nursing model in need of care]. PMID- 1618109 TI - [Fluorouracil as monotherapy or combined with folinic acid in the treatment of metastasizing colorectal carcinoma]. AB - In a prospective randomized multicentre trial 139 patients with metastatic colorectal carcinoma (70 men, 69 women; age 35-81 years) were given palliative treatment with fluorouracil (400 mg/m2 daily for 5 days) alone or combined with folic acid (100 mg/m2 before each dose of fluorouracil). Both groups were comparable in respect of age, sex, Karnofsky index and number of localisations of metastases. The criterion for starting the treatment was progression of the malignancy or clinical symptoms caused by the tumour. Resulting remission rates (fluorouracil monotherapy vs combination with folic acid) were: complete or partial remission, 9 vs 16%; arrest of tumour growth, 20 vs 60%; progression 71 vs 24%. Peripheral side effects, such as stomatitis and diarrhoea, were similarly frequent with the two treatment regimens and reasonably tolerable. Median survival time for the fluorouracil monotherapy was 7.24 months from onset of treatment, and 9.1 months from the time that any metastases were diagnosed. The combination treatment with folic acid achieved a significantly longer median survival time (P less than 0.0001), 14.98 months from treatment onset and 16.3 months from metastasis diagnosis. The higher rate of response and the significantly prolonged survival time signify an improvement of the therapeutic profile of fluorouracil by addition of folic acid in the palliative therapy of colorectal carcinomas. PMID- 1618110 TI - [Primary amyloidosis of the liver]. AB - For 2 years a 72-year-old man had suffered from nonspecific upper abdominal discomfort and hepatomegaly. The gamma-glutamate transaminase concentration was increased to 121 U/l, the erythrocyte sedimentation rate was 80 mm in the first hour. Histological examination of tissue from the enlarged liver (22 cm in the midclavicular line) revealed the diagnosis of amyloidosis. The gastric mucosa, duodenum and rectum were not involved. Two years later ascites developed; six months after this he was again hospitalized in hepatic coma. Now, for the first time, a type IgA-lambda paraprotein was demonstrated by serum immunoelectrophoresis. The patient died of slowly progressing anicteric liver failure after having been ill for a total of 4 1/2 years. At autopsy there were extensive amyloid deposits throughout the liver and spleen so that the structure of these organs was hardly recognizable. The amyloid deposits in the liver were restricted to the glomerular region, while there was no amyloid in the heart. Histochemical tests showed that the deposits were strongly positive to the anti lambda antibody. This was thus a case of primary (AL-lambda) amyloidosis of the liver and spleen which had taken an unusually prolonged course, because the heart was not involved at all and the kidneys only slightly. PMID- 1618111 TI - [Plasminogen activator inhibitor 1--a new thrombosis risk marker]. AB - The plasma activity of plasminogen activator inhibitor 1 (PAI-1) was measured in 278 clinically healthy subjects (98 men, 180 women; mean age 26 [18-50] years). In 198 of them there were factors increasing the risk of thrombosis, such as smoking, over-weight and/or oral contraceptives. PAI-1 activity was within normal range (less than 4 U/ml) in male nonsmokers of normal weight and in female nonsmokers not taking oral contraceptives. In male smokers (5.76 +/- 1.93 U/ml) and in overweight subjects of both sexes (7.49 +/- 1.87 U/ml) PAI-1 was increased up to 10.6 U/ml as an indication of decreased fibrinolysis capacity. Nonsmoking females on oral contraceptives had lower PAI-1 levels (2.72 +/- 0.86 U/ml) than nonsmokers without hormonal intake (3.21 +/- 1.03 U/ml; P less than 0.001). Apparently the increased risk of thrombosis that occurs on oral contraceptives is not due to increased PAI-1 activity. PMID- 1618113 TI - [Surgery in the Ancient Egypt]. PMID- 1618112 TI - [Causes of functional dyspepsia]. PMID- 1618114 TI - [Diagnosis of hereditary hemochromatosis]. PMID- 1618115 TI - [Blood sedimentation reaction and C-reactive protein]. PMID- 1618116 TI - [Dexamethasone in bacterial meningitis]. PMID- 1618117 TI - [Thyroid gland volume and urinary iodine excretion in children 2-16 years of age]. AB - Thyroid volume on ultrasound and urinary iodine excretion in relation to creatinine excretion were determined in 252 children (130 boys, 122 girls; mean age 8.7 [2-16] years) from the central Ruhr area of Germany. The data were compared with those published for children of other regions of Germany and Sweden. Mean thyroid volume in the 2-year olds was 2.0 +/- 0.5 ml, in 4-year olds 2.9 +/- 1.1 ml, in 6-year olds 4.2 +/- 1.9 ml, in 9-year olds 5.2 +/- 1.3 ml and in 13-year olds 8.7 +/- 2.4 ml. Mean iodine excretion for the whole group was 101.0 +/- 41.5 micrograms iodine/g creatinine, in the 13-year olds it was 69 +/- 27 micrograms/g. These values are clearly below those of Swedish children on an adequate iodine intake. The thyroid volume measurements agree reasonably well with those published for children in the region of Germany and are clearly above those of the Swedish children. In 69% of cases the thyroid volume was more than 3 S.D. above the mean for Swedish children. The reported data support the demand for a higher iodine intake of the German population. PMID- 1618119 TI - [Morgagni's hernia: diagnosis and therapy]. AB - A 35-year-old man reported persistent exertional dyspnoea and pressure sensation over the left chest for the last six weeks. On auscultation there were diminished breath sounds over the right base. Chest X-ray demonstrated a 10 cm large ventral paracardiac shadow on the right. Computed tomography suggested a hernia of the foramen of Morgagni; persisting symptoms indicated a laparotomy. This revealed an opening of about 1.5 cm in the right substernocostal triangle through which the entire greater omentum had herniated into the thorax. The omentum was repositioned and the hernial defect closed by direct suture. The postoperative course was without complication and the patient was discharged after seven days. PMID- 1618118 TI - [Diagnosis and course of patients with HIV infections and exclusion of Pneumocystis carinii pneumonia]. AB - 30 patients infected with HIV (20 men, 10 women; mean age 34 [26-54] years), suspected of having Pneumocystis carinii (Pc) pneumonia, had undergone bronchoalveolar lavage which proved negative for Pc. They were then kept under observation for 5 months. No transbronchial biopsy was performed. 27 patients were in stage IV of the HIV infection, and 14 had been on pentamidine prophylaxis. The most frequent diagnosis with the bronchial lavage was bacterial infection (19 patients), next most frequent was mycobacterial infection (6, atypical in 5). A neoplasia (Kaposi sarcoma; non-Hodgkin lymphoma) was found in two, with pulmonary involvement. The diagnosis remained unclear in only three patients who were treated as for Pc pneumonia. The remaining 27 patients did not receive any treatment against Pc. Nonetheless, there were no cases of Pc pneumonia in the 5 months of observation so that bronchoalveolar lavage has a negative predictive value of 90% (27 of 30), high enough to make additional bronchial biopsy unnecessary. PMID- 1618120 TI - [Chronic bromide intoxication caused by bromide-containing combination drugs]. AB - A 49-year-old woman who had noted increasing fatigue and found it difficult to concentrate became confused and uncoordinated with rapid speech. Anxious and suffering from insomnia she had for 6 weeks taken a prescription-free bromide containing drug mixture (daily 0.09 g potassium bromide and 1.8 g sodium bromide), to a total bromide intake of 60 g. The admission diagnosis of chronic bromism was confirmed by a markedly increased serum bromide concentration (325 mg/l). Once she had stopped taking the drug and had increased her salt intake she became symptom-free within 8 days. The case demonstrates that, while chronic bromism has become rare, it should still be included in the differential diagnosis, even after intake of supposedly harmless medication. PMID- 1618122 TI - [Consultation hour for musicians. An interdisciplinary concept]. PMID- 1618121 TI - [Radiological aspects of the craniocervical junction]. PMID- 1618123 TI - [Gestational diabetes]. PMID- 1618124 TI - [Refractory fulminating meningococcal infection]. PMID- 1618125 TI - [Percutaneous biliary drainage and endoscopic jejunostomy for intestinal bile recycling]. PMID- 1618126 TI - [Human insulin and symptoms of hypoglycemia]. PMID- 1618128 TI - Metanephric mesenchyme contains multipotent stem cells whose fate is restricted after induction. AB - At least fourteen epithelial cell types of the mammalian nephron develop from the metanephric mesenchyme. To distinguish whether this single embryological primordium contains a heterogenous population of committed renal cell lines or a multipotent stem cell, the lac-Z gene was introduced into individual renal progenitors by retroviral mediated gene transfer. The differentiated fate of lac Z-tagged daughters derived from single metanephric mesenchymal cells was characterized after cytodifferentiation. We found that the metanephric mesenchyme contains multipotent stem cells that can generate at least three distinct cell types; glomerular, proximal and distal epithelia. After induction the fate of this multipotent cell becomes restricted to populate a single nephron segment. PMID- 1618127 TI - Spatial restriction of AChR gene expression to subsynaptic nuclei. AB - Acetylcholine receptors (AChRs) and the mRNAs encoding the four AChR subunits are highly concentrated in the synaptic region of skeletal myofibers. The initial localization of AChRs to synaptic sites is triggered by the nerve and is caused, in part, by post-translational mechanisms that involve a redistribution of AChR protein in the myotube membrane. We have used transgenic mice that harbor a gene fusion between the murine AChR delta subunit gene and the human growth hormone gene to show that innervation also activates two independent transcriptional pathways that are important for establishing and maintaining this non-uniform distribution of AChR mRNA and protein. One pathway is triggered by signal(s) that are associated with myofiber depolarization, and these signals act to repress delta subunit gene expression in nuclei throughout the myofiber. Denervation of muscle removes this repression and causes activation of delta subunit gene expression in nuclei in non-synaptic regions of the myofiber. A second pathway is triggered by an unknown signal that is associated with the synaptic site, and this signal acts locally to activate delta subunit gene expression only in nuclei within the synaptic region. Synapse-specific expression, however, does not depend upon the continuous presence of the nerve, since transcriptional activation of the delta subunit gene in subsynaptic nuclei persists after denervation. Thus, the nuclei in the synaptic region of multinucleated skeletal myofibers are transcriptionally distinct from nuclei elsewhere in the myofiber, and this spatially restricted transcription pattern is presumably imposed initially by the nerve. PMID- 1618129 TI - Wound closure in foetal rat skin. AB - Foetal rat skin rapidly closes an open wound in organ culture and in vivo, this possibly being unique to organs still in the morphogenetic stage. In the present study, examination was made of morphological changes in foetal rat skin during closure of open wounds inflicted at day 16 of gestation. Phase-contrast microscopy of open-wounded skin cultured in vitro indicated inward spreading of the peripheral skin to be responsible for wound closure. Wound closure in vitro was inhibited by cytochalasin B (10 micrograms/ml), not by hydroxyurea (2 mM), indicating prenatal wound closure to be mediated by regulation of the microfilament system rather than cell proliferation. During wound closure in vitro and in vivo, light and scanning electron microscopy of the peripheral skin showed cells in the periderm, the outermost layer of the foetal epidermis, to elongate centripetally and en masse, whereas the shape of underlying epidermal cells not to change. Numerous spindle-shaped cells and fibrous matrices in the mesenchyme were redistributed, becoming oriented along the wound edge. Following isolation of the mesenchyme and epidermis by treatment with Dispase and separate culturing, the capacity for wound closure in vitro was found to be retained only by the mesenchyme. Cellular activity within the mesenchyme, rather than in the epidermis, would thus appear essential to wound closure in foetal rat. PMID- 1618130 TI - Localized enhancement and repression of the activity of the TGF-beta family member, decapentaplegic, is necessary for dorsal-ventral pattern formation in the Drosophila embryo. AB - Seven zygotically active genes are required for normal patterning of the dorsal 40% of the Drosophila embryo. Among these genes, decapentaplegic (dpp) has the strongest mutant phenotype: in the absence of dpp, all cells in the dorsal and dorsolateral regions of the embryo adopt fates characteristic of more ventrally derived cells (Irish and Gelbart (1987) Genes Dev. 1, 868-879). Here we describe the phenotypes caused by alleles of another of this set of genes, tolloid, and show that tolloid is required for dorsal, but not dorsolateral, pattern. Extragenic suppressors of tolloid mutations were isolated that proved to be mutations that elevate dpp activity. We studied the relationship between tolloid and dpp by analyzing the phenotypes of tolloid embryos with elevated numbers of the dpp gene and found that doubling the dpp+ gene dosage completely suppressed weak tolloid mutants and partially suppressed the phenotypes of tolloid null mutants. We conclude that the function of tolloid is to increase dpp activity. We also examined the effect of doubling dpp+ gene dosage on the phenotypes caused by other mutations affecting dorsal development. Like tolloid, the phenotypes of mutant embryos lacking shrew gene function were suppressed by elevated dpp, indicating that shrew also acts upstream of dpp to increase dpp activity. In contrast, increasing the number of copies of the dpp gene enhanced the short gastrulation (sog) mutant phenotype, causing ventrolateral cells to adopt dorsal fates. This indicates that sog gene product normally blocks dpp activity ventrally. We propose that the tolloid, shrew and sog genes are required to generate a gradient of dpp activity, which directly specifies the pattern of the dorsal 40% of the embryo. PMID- 1618131 TI - Intracellular free Ca2+ changes during physiological polyspermy in amphibian eggs. AB - We have made the first measurements of intracellular free calcium activity ([Ca2+]i) in urodele eggs during physiological polyspermic fertilization. Jellied eggs of the urodele amphibian Pleurodeles waltlii were impaled with intracellular Ca(2+)-selective microelectrodes and inseminated under various conditions of sperm:egg ratio to obtain various degrees of polyspermy. In 17 out of 45 cases the egg [Ca2+]i level (0.41 microM) showed no variation following fertilization. In 28 other cases, however, the egg displayed a slow increase in [Ca2+]i of 0.15 microM, starting around 15 minutes after fertilization and reaching a plateau level around 10 minutes later. The amplitude of the fertilization-associated increase in [Ca2+]i was found to be independent of the number of sperm interacting with the egg surface. Measurements with two Ca(2+)-microelectrodes impaled in single eggs showed that the increase in [Ca2+]i did not simultaneously occur at distinct places within the egg cortex and, in some cases, could be detected by only one of the two microelectrodes. This latter observation, as well as the absence of [Ca2+]i change at fertilization in some experiments, strongly suggested that each sperm interacting with the egg might, at various places, trigger a localized, non-propagating change in [Ca2+]i. Experiments in which eggs were locally inseminated, using a micropipette directed towards the site of impalement of one of the two Ca(2+)-microelectrodes, clearly established that [Ca2+]i changes, although incapable of propagating over the entire egg cortex, might nevertheless travel very slowly over short distances, their amplitude vanishing rapidly as they propagate from around the sites of sperm entry.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618132 TI - Commitment of abdominal neuroblasts in Drosophila to a male or female fate is dependent on genes of the sex-determining hierarchy. AB - Adult specific neurons in the central nervous system of holometabolous insects are generated by the postembryonic divisions of neuronal stem cells (neuroblasts). In the ventral nervous system of Drosophila melanogaster, sex specific divisions by a set of abdominal neuroblasts occur during larval and early pupal stages. Animals mutant for several sex-determining genes were analyzed to determine the genetic regulation of neuroblast commitment to the male or female pattern of division and the time during development when these decisions are made. We have found that the choice of the sexual pathway taken by sex-specific neuroblasts depends on the expression of one of these genes, doublesex (dsx). In the absence of any functional dxs+ products, the sex-specific neuroblasts fail to undergo any postembryonic divisions in male or female larval nervous systems. From the analysis of intersexes generated by dominant alleles of dsx, it has been concluded that the same neuroblasts provide the sex-specific neuroblasts in both male and female central nervous systems. The time when neuroblasts become committed to generate their sex-specific divisions were identified by shifting tra-2ts flies between the male- and female-specifying temperatures at various times during larval development. Neuroblasts become determined to adopt a male or female state at the end of the first larval instar, a time when abdominal neuroblasts enter their first postembryonic S-phase. PMID- 1618133 TI - Motor neuron pathfinding following rhombomere reversals in the chick embryo hindbrain. AB - Motor neurons are segmentally organised in the developing chick hindbrain, with groups of neurons occupying pairs of hindbrain segments or rhombomeres. The branchiomotor nucleus of the trigeminal nerve occupies rhombomeres 2 and 3 (r2 and r3), that of the facial nerve r4 and r5, and that of the glossopharyngeal nerve r6 and r7. Branchiomotor neuron cell bodies lie within the basal plate, forming columns on either side of the ventral midline floor plate. Axons originating in rhombomeres 2, 4 and 6 grow laterally (dorsally) towards the exit points located in the alar plates of these rhombomeres, while axons originating in odd-numbered rhombomeres 3 and 5 grow laterally and then rostrally, crossing a rhombomere boundary to reach their exit point. Examination of the trajectories of motor axons in odd-numbered segments at late stages of development (19-25) showed stereotyped pathways, in which axons grew laterally before making a sharp turn rostrally. During the initial phase of outgrowth (stage 14-15), however, axons had meandering courses and did not grow in a directed fashion towards their exit point. When r3 or r5 was transplanted with reversed rostrocaudal polarity prior to motor axon outgrowth, the majority of axons grew to their appropriate, rostral exit point, despite the inverted neuroepithelial polarity. In r3 reversals, however, there was a considerable increase in the normally small number of axons that grew out via the caudal, r4 exit point. These findings are discussed with relevance to the factors involved in motor neuron specification and axon outgrowth in the developing hindbrain. PMID- 1618134 TI - Effects of the developmental colour mutations silver and recessive spotting on proliferation of diploid and immortal mouse melanocytes in culture. AB - The developmental mouse coat-colour mutations silver (si, chromosome 10) and recessive spotting (rs, chromosome 5, mapping very close to the dominant white spotting or W/c-kit locus), appear to reduce the numbers of functional melanocytes in the skin. They were studied at the cellular level by melanocyte culture. Cellular morphology, differentiation and survival appeared normal. However, both mutations were found to reduce the melanocyte proliferation rate in primary cultures, as measured by [3H]thymidine labelling indices. Two immortal si/si melanocyte lines (designated melan-si1 and melan-si2) and one rs/rs line (melan-rs) were established. Melan-si1 and melan-rs were cloned. All three immortal lines at low passage levels had doubling times significantly greater than those of our other melanocyte lines melan-a, melan-b and melan-c. Thus they retained the phenotype of slow proliferation. PMID- 1618135 TI - Inducible cell ablation in Drosophila by cold-sensitive ricin A chain. AB - We have developed a system for temperature-inducible killing of specific cells in the fruitfly Drosophila melanogaster. The system overcomes many of the limitations of existing cell ablation methods and is in principle applicable to any non-homeothermic eukaryote. Temperature-sensitive and cold-sensitive mutations in the ricin toxin A chain (RTA) of castor bean were generated in yeast. One cold-sensitive mutation, RAcs2, produced temperature-dependent ablation of eye cells in Drosophila when expressed under control of the eye specific sev enhancer. At 29 degrees C, cell death was observed within 7 hours in the developing eye and no obvious toxic effects were observed elsewhere; at 18 degrees C, extremely low toxicity was observed. DNA sequencing of RAcs2 revealed a single amino acid substitution in the RTA active site cleft. PMID- 1618136 TI - Cholinergic neuronal differentiation factors: evidence for the presence of both CNTF-like and non-CNTF-like factors in developing rat footpad. AB - Catecholaminergic sympathetic neurons are able to change their transmitter phenotype during development and to acquire cholinergic properties. Cholinergic sympathetic differentiation is only observed in fibers innervating specific targets like the sweat glands in the rat footpad. A function for ciliary neurotrophic factor (CNTF) in this process has been implied as it is able to induce cholinergic properties (ChAT, VIP) in cultured chick and rat neurons. We show here that a CNTF-like, VIP-inducing activity is present in rat footpads and that its increases 6-fold during the period of cholinergic sympathetic differentiation. Immunohistochemical analysis of P21 rat footpads demonstrated CNTF-like immunoreactivity in Schwann cells but not in sweat glands, the target tissue of cholinergic sympathetic neurons. The expression of this factor in footpads seems to be dependent on the presence of intact nerve axons, as nerve transection results in a loss of CNTF-like cholinergic activity and immunoreactivity. Immunoprecipitation experiments with rat footpad extracts provided evidence for the presence of ChAT-inducing factors other than CNTF, which may independently or together with CNTF be involved in the determination of sympathetic neuron phenotype. PMID- 1618137 TI - Organization and regulation of cortical microtubules during the first cell cycle of Xenopus eggs. AB - Anti-tubulin antibodies and confocal immunofluorescence microscopy were used to examine the organization and regulation of cytoplasmic and cortical microtubules during the first cell cycle of fertilized Xenopus eggs. Appearance of microtubules in the egg cortex temporally coincided with the outgrowth of the sperm aster. Microtubules of the sperm aster first reached the animal cortex at 0.25, (times normalized to first cleavage), forming a radially organized array of cortical microtubules. A disordered network of microtubules was apparent in the vegetal cortex as early as 0.35. Cortical microtubule networks of both animal and vegetal hemispheres were reorganized at times corresponding to the cortical rotation responsible for specification of the dorsal-ventral (D-V) axis. Optical sections suggest that the cortical microtubules are continuous with the microtubules of the sperm aster in fertilized eggs, or an extensive activation aster in activated eggs. Neither assembly and organization, nor disassembly of the cortical microtubules coincided with MPF activation during mitosis. However, cycloheximide or 6-dimethylaminopurine, which arrest fertilized eggs at interphase, blocked cortical microtubule disassembly. Injection of p13, a protein that specifically inhibits MPF activation, delayed or inhibited cortical microtubule breakdown. In contrast, eggs injected with cyc delta 90, a truncated cyclin that arrest eggs in M-phase, showed normal microtubule disassembly. Finally, injection of partially purified MPF into cycloheximide-arrested eggs induced cortical microtubule breakdown. These results suggest that, despite a lack of temporal coincidence, breakdown of the cortical microtubules is dependent on the activation of MPF. PMID- 1618138 TI - Expression of a novel FGF in the Xenopus embryo. A new candidate inducing factor for mesoderm formation and anteroposterior specification. AB - We have cloned and sequenced a new member of the fibroblast growth factor family from Xenopus laevis embryo cDNA. It is most closely related to both mammalian kFGF (FGF-4) and FGF-6 but as it is not clear whether it is a true homologue of either of these genes we provisionally refer to it as XeFGF (Xenopus embryonic FGF). Two sequences were obtained, differing by 11% in derived amino acid sequence, which probably represent pseudotetraploid variants. Both the sequence and the behaviour of in vitro translated protein indicates that, unlike bFGF (FGF 2), XeFGF is a secreted molecule. Recombinant XeFGF protein has mesoderm-inducing activity with a specific activity similar to bFGF. XeFGF mRNA is expressed maternally and zygotically with a peak during the gastrula stage. Both probe protection and in situ hybridization showed that the zygotic expression is concentrated in the posterior of the body axis and later in the tailbud. Later domains of expression were found near the midbrain/hindbrain boundary and at low levels in the myotomes. Because of its biological properties and expression pattern, XeFGF is a good candidate for an inducing factor with possible roles both in mesoderm induction at the blastula stage and in the formation of the anteroposterior axis at the gastrula stage. PMID- 1618139 TI - Neural induction and regionalisation in the chick embryo. AB - Induction and regionalisation of the chick nervous system were investigated by transplanting Hensen's node into the extra-embryonic region (area opaca margin) of a host embryo. Chick/quail chimaeras were used to determine the contributions of host and donor tissue to the supernumerary axis, and three molecular markers, Engrailed, neurofilaments (antibody 3A10) and XlHbox1/Hox3.3 were used to aid the identification of particular regions of the ectopic axis. We find that the age of the node determines the regions of the nervous system that form: young nodes (stages 2-4) induced both anterior and posterior nervous system, while older nodes (stages 5-6) have reduced inducing ability and generate only posterior nervous system. By varying the age of the host embryo, we show that the competence of the epiblast to respond to neural induction declines after stage 4. We conclude that during normal development, the initial steps of neural induction take place before stage 4 and that anteroposterior regionalisation of the nervous system may be a later process, perhaps associated with the differentiating notochord. We also speculate that the mechanisms responsible for induction of head CNS differ from those that generate the spinal cord: the trunk CNS could arise by homeogenetic induction by anterior CNS or by elongation of neural primordia that are induced very early. PMID- 1618140 TI - Fgf-4 expression during gastrulation, myogenesis, limb and tooth development in the mouse. AB - Fgf-4, initially isolated as a transforming gene from human tumors, is a member of the Fibroblast Growth Factor (FGF) family. It has previously been shown by northern blot hybridization analysis to be expressed in teratocarcinoma and embryonic stem cells, suggesting that it plays a role in embryonic development. We have carried out an RNA in situ hybridization analysis of Fgf-4 expression in the developing mouse embryo, from fertilization through the 14th day of gestation (E14.5). Our results show that Fgf-4 RNA is first detected at the late blastocyst stage in cells that give rise to all of the embryonic lineages (inner cell mass cells). During the early stages of gastrulation, expression becomes restricted to the primitive streak where mesoderm and definitive endoderm are formed. Expression continues in the distal (rostral) two-thirds of the streak through approx. E10, and then is detected in the tail bud, which replaces the streak as the primary source of mesoderm. Additional sites of expression are found after the three primary germ layers are established and organogenesis begins. Fgf-4 RNA is detected transiently in the branchial arch units, the somitic myotome, the apical ectodermal ridge of the developing limb bud and the tooth bud, suggesting that the gene has multiple roles during embryogenesis. These results are compared with the expression patterns of other FGF genes. Taken together, the data suggest that individual members of the gene family are expressed sequentially in developmental pathways such as mesoderm formation and myogenesis, and play a role in specific epithelial-mesenchymal interactions. PMID- 1618141 TI - Early mRNAs, spatially restricted along the animal-vegetal axis of sea urchin embryos, include one encoding a protein related to tolloid and BMP-1. AB - The cloning and characterization of cDNAs representing four genes or small gene families that are coordinately expressed in a spatially restricted pattern during the very early blastula (VEB) stage of sea urchin development are presented. The VEB genes encode multiple transcripts that are expressed transiently in embryos of Strongylocentrotus purpuratus between 16-cell stage and hatching, with peak abundance 12 to 15 hours post-fertilization (approximately 150-250 cells). The VEB transcripts share the same spatial pattern in the early blastula embryo: they are asymmetrically distributed along the animal-vegetal axis but their distribution around this axis is uniform. Thus, the VEB transcripts are the earliest messages to reveal asymmetry along the primary axis in the sea urchin embryo. The temporal and spatial patterns of VEB transcript accumulation are not consistent with involvement of these gene products in cell division or in tissue specific functions. Furthermore, VEB messages cannot be detected in either ovary or adult tissues, suggesting that these genes function exclusively during embryogenesis. We suggest that the VEB genes function in constructing the early blastula. Two VEB genes encode metalloendoproteases: one (SpHE) is hatching enzyme and the other (SpAN) is similar to bone morphogenetic protein-1 (BMP-1; Wozney et al., Science 242: 1528-1534, 1988) and the Tolloid gene product (tld) (Shimell et al., Cell 67: 459-482, 1991). Several lines of evidence suggest that the VEB genes are regulated directly by factors or regulatory activities localized along the maternally specificed animal-vegetal axis. PMID- 1618142 TI - Isolation of temperature-sensitive diphtheria toxins in yeast and their effects on Drosophila cells. AB - We have isolated temperature-sensitive diphtheria toxins (DT-A(ts)) to develop a method that allows temporal impedement of cellular functions. Four DT-A(ts) genes were isolated in a mutagenesis screen using the yeast, Saccharomyces cerevisiae. When expressed in yeast, these DT-A(ts) arrest growth at 18 degrees C but not at 30 degrees C. Three DT-A(ts) were subsequently tested in the R1-R6 photoreceptor cells of transgenic fruit flies, Drosophila melanogaster. The toxins show similar temperature dependence in both organisms, suggesting that they may be useful in a wide range of non-homeothermic species. DNA sequence analysis revealed that three of the four DT-A(ts) mutations are novel. Interestingly, the fourth DT-A(ts) carries the same point mutation as the extensively characterized CRM197, an ADP ribosyltransferase-defective form of diphtheria toxin. PMID- 1618143 TI - Compensatory synaptic growth in the rod terminals as a sequel to partial photoreceptor cell loss in the retina of chimaeric mice. AB - In the retina of chimaeric mice of rd and wild-type genotypic combination, selective loss of rd/rd photoreceptor cells, after initial development, leads to a mosaic retina with variable amounts of normal photoreceptor cells present over the retinal surface. In some of the rod terminals of these retinas the synaptic complexes with the second order retinal neurons are seen to contain multiple synaptic ribbons and an increased number of profiles of the postsynaptic elements. These changes are observed only in the rod terminals and not in the cone pedicles. Computer aided three-dimensional reconstruction of the altered synapses shows that these changes result from an increase in the number of synaptic sites, characterized by multiplication of the synaptic ribbons and enlargement of the second order neuronal processes. A quantitative analysis of such synapses, based on serial electron micrographs, shows that these are most frequently located in the retinal regions of the chimaeric individuals that have suffered maximum photoreceptor cell loss. Thus synaptic growth appears to take place as a reaction to the reduction of afferent input to the postsynaptic components. These findings demonstrate persistent synaptic plasticity in the rod terminals of mammalian retina during the maturational phase of late postnatal development. Compensatory synaptic growth in the rod terminals, as recorded here, can have important implications for the maintenance of visual sensitivity in the diseased or ageing retina. PMID- 1618144 TI - Pathfinding by cranial nerve VII (facial) motorneurons in the chick hindbrain. AB - Cranial nerve VII (facial) motorneurons begin extending axons through rhombomeres 4 and 5 (R4 and R5) in the chick hindbrain on the second day of incubation. Without crossing the midline, facial motorneuron axons extend laterally from a ventromedial cell body location. All facial motorneuron axons leave the hindbrain through a discrete exit site in R4. To examine the importance of the exit site in R4 on motorneuron pathfinding, we ablated R4 before motorneuron axonogenesis. We find that mechanisms intrinsic to R5 direct the initial lateral orientation of R5 motorneuron axons. Upon reaching a particular lateral position, all R5 motorneuron axons must turn. In normal embryos the axons all turn rostrally to reach the nerve exit in R4. In embryos with R4 ablated, sometimes the axons turn rostrally and sometimes they turn caudally. A model combining permissive fields and chemotropic cues is presented to account for our observations. PMID- 1618145 TI - Altered mitotic domains reveal fate map changes in Drosophila embryos mutant for zygotic dorsoventral patterning genes. AB - The spatial and temporal pattern of mitoses during the fourteenth nuclear cycle in a Drosophila embryo reflects differences in cell identities. We have analysed the domains of mitotic division in zygotic mutants that exhibit defects in larval cuticular pattern along the dorsoventral axis. This is a powerful means of fate mapping mutant embryos, as the altered position of mitotic domains in the dorsoventral pattern mutants correlate with their late cuticular phenotypes. In the mutants twist and snail, which fail to differentiate the ventrally derived mesoderm, mitoses specific to the mesoderm are absent. The lateral mesectodermal domain shows a partial ventral shift in twist mutants but a proportion of ventral cells do not behave characteristically, suggesting that twist has a positive role in the establishment of the mesoderm. In contrast, snail is required to repress mesectodermal fates in cells of the presumptive mesoderm. In the absence of both genes, the mesodermal and the mesectodermal anlage are deleted. Mutations at five loci delete specific pattern elements in the dorsal half of the embryo and cause partial ventralization. Mutations in the genes zerknullt and shrew affect cell division only in the dorsalmost cells corresponding to the amnioserosa, while the genes tolloid, screw and decapentaplegic (dpp) affect divisions in both the prospective amnioserosa and the dorsal epidermis. We demonstrate that in each of these mutants dorsally placed mitotic domains are absent and this effect is correlated with an expansion and dorsal shift in the position of more ventral domains. The loss of activity in each of the five genes results in qualitatively similar alterations in the mitotic pattern; mutations with stronger ventralizing phenotypes affect increasingly greater subsets of the dorsal cells. Double mutant analysis indicates that these genes act in a concerted manner to specify dorsal fates. The correlation between phenotypic strength and the progressive loss of dorsal pattern elements in the ventralized mutants, suggests that one of these gene products, perhaps dpp, may provide positional information in a graded manner. PMID- 1618146 TI - Pathfinding by zebrafish motoneurons in the absence of normal pioneer axons. AB - Individually identified primary motoneurons of the zebrafish embryo pioneer cell specific peripheral motor nerves. Later, the growth cones of secondary motoneurons extend along pathways pioneered by primary motor axons. To learn whether primary motor axons are required for pathway navigation by secondary motoneurons, we ablated primary motoneurons and examined subsequent pathfinding by the growth cones of secondary motoneurons. We found that ablation of the primary motoneuron that pioneers the ventral nerve delayed ventral nerve formation, but a normal-appearing nerve eventually formed. Therefore, the secondary motoneurons that extend axons in the ventral nerve were able to pioneer that pathway in the absence of the pathway-specific primary motoneuron. In contrast, in the absence of the primary motoneuron that normally pioneers the dorsal nerve, secondary motoneurons did not pioneer a nerve in the normal location, instead they formed dorsal nerves in an atypical position. This difference in the ability of these two groups of motoneurons to pioneer their normal pathways suggests that the guidance rules followed by their growth cones may be very different. Furthermore, the observation that the atypical dorsal nerves formed in a consistent incorrect location suggests that the growth cones of the secondary motoneurons that extend dorsally make hierarchical pathway choices. PMID- 1618147 TI - Transforming growth factor-alpha (TGF-alpha) and insulin gene expression in human fetal pancreas. AB - Transforming growth factor-alpha (TGF-alpha) mRNA is expressed in several pancreatic cancer cell lines, but its expression during normal fetal pancreas development has not been studied. We investigated the expression of TGF-alpha, its receptor (EGF-R) and insulin mRNA and their corresponding peptides in human fetal pancreata (15-20 gestation weeks). Polymerase chain reaction (PCR) and RNAase protection analysis revealed that TGF-alpha and insulin mRNAs were detectable in pancreas during the developmental span studied. In northern blot analysis a single band of 4.8 kilobases (kb) corresponding to the TGF-alpha transcript and a 0.6 kb for the insulin mRNA were detected in the pancreas. Using in situ hybridization, TGF-alpha mRNA expression was seen in a low copy number in both the exo- and endocrine pancreas. By immunohistochemistry TGF-alpha immunoreactive cells were detected in the ducts, acini and islets showing that the mRNA was translated into protein. By contrast, insulin transcripts were detected in a high copy number, restricted to the islets of Langerhans. However, monoclonal insulin antibody detected less insulin containing cells than could be expected from the mRNA pattern suggesting that fetal beta-cells rapidly secrete insulin instead of storing it in the secretory granules. Alternatively, the translation of insulin mRNA could be inefficient. By double labeling the pancreas sections with polyclonal TGF-alpha antiserum and monoclonal insulin antibody the TGF-alpha- and insulin-like immunoreactivity was localized to beta-cells. Furthermore, mRNA for the TGF-alpha receptor, EGF-R, together with EGF-R immunoreactive cells were also present in pancreas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618148 TI - Skeletal muscle phenotypes initiated by ectopic MyoD in transgenic mouse heart. AB - Forced expression of the myogenic regulatory gene MyoD in many types of cultured cells initiates their conversion into skeletal muscle. It is not known, however, if MyoD expression serves to activate all or part of the skeletal muscle program in vivo during animal development, nor is it known how limiting the influences of cellular environment may be on the regulatory effects of MyoD. To begin to address these issues, we have produced transgenic mice which express MyoD in developing heart, where neither MyoD nor its three close relatives--myogenin, Myf 5, and MRF4/herculin/Myf-6--are normally expressed. The resulting gross phenotype in offspring from multiple, independent transgenic founders includes abnormal heart morphology and ultimately leads to death. At the molecular level, affected hearts exhibit activation of skeletal muscle-specific regulatory as well as structural genes. We conclude that MyoD is able to initiate the program that leads to skeletal muscle differentiation during mouse development, even in the presence of the ongoing cardiac differentiation program. Thus, targeted misexpression of this tissue-specific regulator during mammalian embryogenesis can activate, either directly or indirectly, a diverse set of genes normally restricted to a different cell lineage and a different cellular environment. PMID- 1618149 TI - Prenatal expression of the growth hormone (GH) receptor/binding protein in the rat: a role for GH in embryonic and fetal development? AB - Although fetal growth is generally considered to be independent of pituitary growth hormone (GH), it is possible that pituitary GH plays a modulatory role in organ development or that a GH-like substance of non pituitary origin may influence fetal growth through the GH receptor. Accordingly, we have used immunohistochemistry, northern blot analysis, the reverse transcriptase polymerase chain reaction and solution hybridization to study the ontogeny of the GH receptor/binding protein (BP) from the 12-day-old embryo (E12) to the E18 rat fetus. GH receptor/BP immunoreactivity was observed in all major organ systems of the E18 rat fetus and was not preferentially associated with any germ layer derivative. A general increase in GH receptor/BP immunoreactivity was evident from E12 to E18, with a marked increase occurring between E16 and E18. Hemangioblastic tissue was, however, strongly or intensely immunoreactive at all stages of development, as was the placenta. Most noteworthy of the other tissues expressing GH receptor/BP immunoreactivity by day 18 were skeletal and smooth muscle, chondroprogenitor cells, epithelial lining cells, neuronal ganglia, ependymal cells and the adrenal cortex. In the placenta, the most prominent immunoreactivity was associated with decidual cells. Total RNA was isolated from E12 to E18 rat fetuses and adult rat liver. Northern hybridization with a 35S labelled rat GH receptor cRNA probe revealed that 3.9 kb and 1.2 kb transcripts complementary to the rat GH receptor riboprobe are present from at least E16. The existence of GH receptor mRNA at E12 and E14 was demonstrated by the polymerase chain reaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618150 TI - Cellular and extracellular involvement in the regeneration of the rat lower vibrissa follicle. AB - The sequence of events leading to the reconstruction of a fibre-producing hair follicle, after microsurgical amputation of the lower follicle bulb, has been detailed by immunohistology and electron microscopy. The initial response was essentially found to be a wound reaction, in that hyperproliferative follicle epidermis quickly spread to below the level of amputation--associated with downward movement of mesenchymal (or dermal) sheath cells. Fibronectin was prominent in both dermis and epidermis at this stage and, as in wound repair, preceded laminin and type IV collagen in covering the lower dermal-epidermal junction. Once a new basal line of epidermis and a complete basement membrane were established, laminin and type IV collagen were detected below this junction and within the prospective papilla-forming mesenchyme. This coincided with ultrastructural observations of profuse sub-basement membrane extracellular material in the region of new papilla formation. The glassy membrane displayed extensive ultrastructural modifications at its lower level, and these corresponded with localized variations in staining intensities for all three antibodies over time. The membrane hung below the level of the epidermis, and was crossed by migrating cells from the mesenchymal dermal sheath of the follicle - it acted to segregate the inner group of follicular dermal cells from wound fibroblasts. Extracellular matrix may be a mediator of the dermal-epidermal interactions associated with this hair follicle regeneration phenomenon. PMID- 1618151 TI - Diffusible rod-promoting signals in the developing rat retina. AB - We previously developed a reaggregate cell culture system in which embryonic rat retinal neuroepithelial cells proliferate and give rise to opsin-expressing rod photoreceptor cells (rods) on the same schedule in vitro as they do in vivo. We showed that the proportion of neuroepithelial cells in the embryonic day 15 (E15) retina that differentiated into opsin+ rods after 5-6 days in such cultures increased by approximately 40-fold when the E15 cells were cultured in the presence of an excess of postnatal day 1 (P1) neural retinal cells. In the present study, we have further analyzed this rod-promoting activity of neonatal neural retinal cells. We show that the activity is mediated by a diffusible signal(s) that seems to act over a relatively short distance. Whereas neonatal (P1-P3) neural retina has rod-promoting activity, E15 and adult neural retina, neonatal thymus, cerebrum and cerebellum do not. Finally, we show that neonatal neural retina promotes rod but not amacrine cell development. PMID- 1618152 TI - Transforming growth factor-beta 1, -beta 2 and -beta 3 in cartilage and bone cells during endochondral ossification in the chick. AB - The localization of TGF-beta 1, -beta 2 and -beta 3 was studied in the growth plate, epiphysis and metaphysis of the tibiotarsus of three-week-old chicks. The different TGF-beta isoforms were localized to hypertrophic chondrocytes, chondroclasts, osteoblasts and osteoclasts using immunohistochemical staining analysis with specific TGF-beta antibodies. TGF-betas in osteoclasts and chondroclasts were restricted to those cells located on the respective matrices. TGF-beta 3 localization was mainly cytoplasmic in the transitional (early hypertrophic) chondrocytes, but nuclear staining was also detected in some proliferating chondrocytes. The cell-specific localization of these TGF-beta isoforms supports the hypothesis that TGF-beta has a role in the coupling of new bone formation to bone and cartilage matrix resorption during osteochondral development and suggests that TGF-beta may be a marker of chondrocyte differentiation. TGF-beta localization preceded a marked increase in type II collagen mRNA expression in transitional chondrocytes, suggesting a role for TGF beta in the induction of synthesis of extracellular matrix. PMID- 1618153 TI - Regeneration of dopaminergic neurons in goldfish retina. AB - The conditions necessary to trigger regeneration of dopaminergic neurons were investigated in the goldfish retina. Intraocular injection of 6-hydroxydopamine (6-OHDA) was used to destroy dopaminergic neurons, and neuronal regeneration was monitored by injections of the thymidine analog bromodeoxyuridine (BUdR). Regenerated dopaminergic neurons, (identified by double-labeling with anti tyrosine hydroxylase and anti-BUdR antibodies) were found within 3 weeks after 2 injections of 0.6 mg/ml 6-OHDA (estimated intraocular concentration), but not after injection of lower doses. All retinas with regenerated dopaminergic neurons also contained other types of regenerated neurons, including cones and ganglion cells, consistent with nuclear counts which revealed non-selective cell loss (34 36%) in both the outer and inner nuclear layers after exposure to the high dose, but not lower doses of 6-OHDA. Regenerated neurons were produced by clusters of dividing neuroepithelial cells probably derived from rod precursors in the outer nuclear layer. These results demonstrate that dopaminergic neurons will not regenerate after they are selectively ablated but only as part of a developmental process that involves generation of multiple cell types. PMID- 1618154 TI - Evolutionary dissociation between cleavage, cell lineage and embryonic axes in sea urchin embryos. AB - Using vital dye staining and the microinjection of fluorescent cell lineage autonomous tracers, the relationship between the first cleavage plane and the prospective larval dorsoventral axis was examined in several sea urchin species, including: Strongylocentrotus purpuratus, S. droebachiensis, Lytechinus pictus, Clypeaster rosaceus, Heliocidaris tuberculata and H. erythrogramma. The results indicate that there is no single relationship between the early cleavage pattern and the dorsoventral axis for all sea urchins; however, specific relationships exist for individual species. In S. purpuratus the first cleavage plane occurs at an angle 45 degrees clockwise with respect to the prospective dorsoventral axis in most cases, as viewed from the animal pole. On the other hand, in S. droebachiensis, L. pictus and H. tuberculata, the first cleavage plane generally corresponds with the plane of bilateral symmetry. There does not appear to be a predominant relationship between the first cleavage plane and the dorsoventral axis in C. rosaceus. In the direct-developing sea urchin H. erythrogramma the first cleavage plane bisects the dorsoventral axis through the frontal plane. Clearly, evolutionary differences have arisen in the relationship between cleavage pattern and developmental axes. Therefore, the mechanism of cell determination is not necessarily tied to any particular pattern of cell cleavage, but to an underlying framework of axial systems resident within sea urchin eggs and embryos. PMID- 1618155 TI - Regulation of proneural gene expression and cell fate during neuroblast segregation in the Drosophila embryo. AB - The Drosophila embryonic central nervous system develops from sets of progenitor neuroblasts which segregate from the neuroectoderm during early embryogenesis. Cells within this region can follow either the neural or epidermal developmental pathway, a decision guided by two opposing classes of genes. The proneural genes, including the members of the achaete-scute complex (AS-C), promote neurogenesis, while the neurogenic genes prevent neurogenesis and facilitate epidermal development. To understand the role that proneural gene expression and regulation play in the choice between neurogenesis and epidermogenesis, we examined the temporal and spatial expression pattern of the achaete (ac) regulatory protein in normal and neurogenic mutant embryos. The ac protein is first expressed in a repeating pattern of four ectodermal cell clusters per hemisegment. Even though 5 7 cells initially express ac in each cluster, only one, the neuroblast, continues to express ac. The repression of ac in the remaining cells of the cluster requires zygotic neurogenic gene function. In embryos lacking any one of five genes, the restriction of ac expression to single cells does not occur; instead, all cells of each cluster continue to express ac, enlarge, delaminate and become neuroblasts. It appears that one key function of the neurogenic genes is to silence proneural gene expression within the nonsegregating cells of the initial ectodermal clusters, thereby permitting epidermal development. PMID- 1618156 TI - A temporally regulated, diffusible activity is required for rod photoreceptor development in vitro. AB - The retina is a relatively simple and well-characterized CNS structure in which cell-cell interactions have been hypothesized to influence cell type determination. By manipulating cell density in serum-free cultures we show that rat rod photoreceptor development requires a diffusible activity produced by neonatal retinal cells. This effect is not mediated by changes in cell survival or mitosis. Production of the rod promoting activity varies with developmental stage and is temporally correlated with the timing of rod generation in vivo. In low density cultures, which do not support rod development, an increased fraction of cells stain with an antibody specific for another retinal neuron, the bipolar cell. Thus, the diffusible rod promoting activity may influence cell fate determination, and not only terminal differentiation. These results provide an approach for the molecular characterization of developmentally important signals in the vertebrate retina. PMID- 1618157 TI - Evidence for endogenous proteases, mRNA level and insulin as multiple mechanisms of N-cadherin down-regulation during retinal development. AB - Our previous studies of the role of cell adhesion in retinal development have focused on the expression and function of N-cadherin, the predominant calcium dependent intercellular adhesion protein of neural tissues. During the course of retinal development, N-cadherin expression undergoes significant qualitative and quantitative changes in its pattern of expression, most prominently a sharp down regulation of expression throughout most of the retina. The present studies were directed at investigating the epigenetic mechanisms that could mediate this loss of N-cadherin from the retina. Using an in vitro intact retinal organ culture system, results were obtained which suggest that insulin enhances the down regulation of N-cadherin expression in a protein-synthesis-dependent fashion. Furthermore, the metalloprotease inhibitor 1,10-phenanthroline inhibits the loss of N-cadherin from the retina. While N-cadherin is down-regulated in organ culture, other cell adhesion molecules, which are not down-regulated in vivo, are also not down-regulated in organ culture. The defined organ culture medium conditioned by the retina accumulates both a soluble 90 x 10(3) M(r) N-terminal fragment of N-cadherin as well as a number of secreted proteases. Both of these components are also shown to be present in vivo in the vitreous humor. Northern blot analysis indicates a single mRNA encoding N-cadherin in the retina and no evidence for a second message that could encode the 90 x 10(3) M(r) fragment. However, the amount of N-cadherin mRNA detectable on northern blots decreases during development. The results reported here suggest that the down-regulation of N-cadherin that occurs during retinal development is possibly mediated by multiple mechanisms, which include turnover at the cell surface mediated by endogenous proteolysis, reduced levels of N-cadherin mRNA and modulation by growth factors. PMID- 1618158 TI - Evidence of a role for endogenous electrical fields in chick embryo development. AB - We have tested directly the hypothesis that the endogenous electrical field in the chick embryo plays a causal role in development. Conductive implants, which shunt currents out of the embryo and thus alter the internal field, were placed under the dorsal skin at the mid-trunk level of stage 11-15 embryos. Currents leaving the posterior intestinal portal (p.i.p.) of these embryos were reduced by an average of 30%. Control embryos receiving non-conductive implants showed no change in p.i.p. currents. In the group receiving current shunts, 92% of the embryos exhibited some developmental abnormality. Only 11% of the control group displayed defects. The most common defect in the experimental group (81%) was in tail development. Tail defects ranged from complete absence to the formation of a normal length, but morphologically abnormal tail. Internally, tail structures (neural tube, notochord and somites) were frequently absent or aberrantly formed. In 33% of the experimental embryos, the notochord continued lengthening in the absence of any other tail development. This led to the formation of ourenteric outgrowths from the hindgut. Defects in limb bud and head development were also found in experimentally treated embryos, but at a much lower frequency than tail defects. The abnormalities observed in experimental embryos were very similar to those produced naturally in rumpless mutant chicks. A vibrating probe analysis of these mutants (from both dominant and recessive strains) showed that currents leaving the p.i.p. were significantly lower in phenotypically abnormal mutants than in wild-type and phenotypically normal mutant embryos from both strains. There was no apparent correlation between the average transepithelial potential (TEP) of these mutants and the development of tail abnormalities. The possible role of endogenous electrical fields in chick tail development is discussed. PMID- 1618159 TI - Embryonic cytoplasmic extracts rescue murine androgenones to the blastocyst stage. AB - Androgenones (paternally derived genome) show a significant inability to form a blastocoele cavity. Eighty percent of these embryos die or arrest at earlier stages. Factor(s) from both normal and parthenogenetic late preimplantation embryos injected into each blastomere of androgenetic 4-cell stage can rescue more than twice as many to the blastocyst stage (47.2% versus 19.2% for non injected androgenones). This factor(s) becomes available beginning at the 4-cell stage and is titratable. Injected total cytoplasmic mRNA will also cause a rescue response. Isolating this specific factor message(s) will permit the eventual cloning of possibly the earliest parentally imprinted gene(s) expressed during development. PMID- 1618160 TI - Anatomy of the steroid receptor zinc finger region. PMID- 1618161 TI - The molecular biology of RU486. Is there a role for antiprogestins in the treatment of breast cancer? PMID- 1618162 TI - The molecular biology of thyroid peroxidase: cloning, expression and role as autoantigen in autoimmune thyroid disease. PMID- 1618163 TI - Dissociation of dopamine from its receptor as a signal in the pleiotropic hypothalamic regulation of prolactin secretion. AB - We have reviewed the literature, which supports an important role for dopamine withdrawal in the regulation of PRL secretion. Concentrations of dopamine in the hypophyseal portal circulation are sufficient to occupy the majority of dopamine receptors (1) and tonically suppress PRL secretion (20-26). Brief escapes from dopaminergic regulation associated with the secretion of PRL have been observed (37-41). Therefore, dopamine regulates secretion of PRL both by occupancy of, as well as dissociation from, specific D2 dopamine receptors. The rapid off rate from its receptor (2) is consistent with signals transmitted through brief decreases in dopamine concentration. The removal of dopamine for 10 min results in increases in intracellular cAMP and presumably activation of protein kinase A (39, 138) as well as activation of phospholipase C (137, 138) and protein kinase C (136). The removal of dopamine results directly in the release of PRL (37-41). Furthermore, the brief removal of dopamine results in the long-term potentiation of the PRL-releasing action of TRH (38-40). The potentiating action of dopamine withdrawal appears to be mediated by the activation of protein kinase A since pretreatment with VIP, a hormone that signals via protein kinase A, also potentiates the action of TRH (39). TRH stimulates PRL release via Ca2+/protein kinase C (177-184). The potentiating action of dopamine removal is selective for the Ca2+/protein kinase C pathway since dopamine removal does not potentiate the PRL-secreting action of VIP (38, 87, 92). The action of TRH is potentiated up to 30 min after the return of dopamine and the suppression of PRL to basal levels (38). In Fig. 10, dopamine dissociation from its receptor or VIP association to its receptor are shown separated by a broken line to indicate that by the time the potentiation of the action of TRH is tested, either dopamine is again occupying its receptor or VIP is no longer present. Therefore, the effect of protein kinase A activation is remembered by the lactotroph. We hypothesize that the responsiveness of the cell to TRH is potentiated by the phosphorylation of proteins by protein kinase A. Two potential substrates for protein kinase A are voltage-dependent Ca2+ channels and protein phosphatase inhibitors that would prolong the action of protein kinase C. When TRH occupies its receptor, intracellular Ca2+ levels are increased first from intracellular stores and subsequently by extracellular Ca2+ influx (187-189). Intracellular Ca2+ is mobilized by increased levels of IP3(128). Extracellular Ca2+ enters the lactotroph via voltage-dependent Ca2+ channels (189, 190).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1618164 TI - The impact of gonadal steroid hormone action on growth hormone secretion during childhood and adolescence. PMID- 1618166 TI - Brain and pituitary angiotensin. PMID- 1618165 TI - Physiology and molecular genetics of mutations that increase ovulation rate in sheep. PMID- 1618167 TI - Counterpoint: molecular analysis of the angiotensin II receptor. PMID- 1618169 TI - Adaptation in patients with chronic rheumatoid arthritis: application of a general model. AB - We derived a model of appraisal, coping, and adaptation in patients with rheumatoid arthritis (RA) from the more general theory of Lazarus and Folkman (1984) and examined this model using a longitudinal data set spanning 4 years and involving 239 RA patients (of whom 157 contributed to the primary analyses, with the remainder contributing to various follow-up analyses). This model attempted to identify the short- and long-term adaptational consequences of coping as well as the antecedents (appraisals, beliefs, social support, disease activity, etc.) that promote particular coping styles. Interrelations among the variables were examined using path-analytic techniques. Many observed relations were consistent with the model. Significant relations were subjected to more stringent analyses examining the ability of hypothesized causal variables to predict changes in outcome variables 1 year later. These analyses provided additional support for many observed relations and suggested the existence of a vicious cycle involving helplessness appraisals, passive coping with pain, and psychosocial impairment that promotes maladaptation in the face of RA. Theoretical implications, strengths, and limitations of the study are discussed. PMID- 1618168 TI - Hostility and health: current status of a psychosomatic hypothesis. AB - Recent research has renewed interest in the potential influence of hostility on physical health. This review indicates that the evidence available from prospective studies, although not entirely consistent, suggests that hostile persons may be at increased risk for subsequent coronary heart disease and other life-threatening illnesses. Further, several plausible mechanisms possibly linking hostility and health have been articulated and subjected to initial evaluation. Hostile individuals display heightened physiological reactivity in some situations, report greater degrees of interpersonal conflict and less social support, and may have more unhealthy daily habits. Additional research is needed, and it must address a variety of past conceptual and methodological limitations. Perhaps the most central of these concerns are the assessment of individual differences in hostility and the role of social contexts in the psychosomatic process. PMID- 1618171 TI - A model of the precaution adoption process: evidence from home radon testing. AB - We present the precaution adoption process model--a stage theory consisting of seven distinct states between ignorance and completed preventive action. The stages are "unaware of the issue," "aware of the issue but not personally engaged," "engaged and deciding what to do," "planning to act but not yet having acted," "having decided not to act," "acting," and "maintenance." The theory asserts that these stages represent qualitatively different patterns of behavior, beliefs, and experience and that the factors that produce transitions between stages vary depending on the specific transition being considered. Data from seven studies of home radon testing are examined to test some of the claims made by this model. Stage theories of protective behavior are contrasted with theories that see precaution adoption in terms of movement along a single continuum of action likelihood. PMID- 1618170 TI - Emotional inhibition in essential hypertension: obstacle to communication during medical visits? AB - A substantial literature on the "hypertensive personality" links essential hypertension (EH) with the suppression of negative emotions, implying that suppression may elevate blood pressure. Yet affective inhibition might also impair communication with health care providers and exacerbate EH by limiting therapeutic collaboration. We studied 542 patient-physician interviews from a national sample to see if patients with EH (n = 203) were less likely to exhibit negative emotions than normotensive patients (n = 339) as rated by their physicians and independent observers. EH patients did not differ from others on self-rated emotional or physical health. However, physicians were less accurate in characterizing the emotional states of EH patients than those of normotensive patients, and they rated EH patients as exhibiting fewer signs of distress during the visit. Independent observers also judged the EH patients as less distressed than normotensives, thereby validating the physicians' appraisals. Content analysis disclosed that physicians paid less attention to psychosocial concerns and concentrated on biomedical matters to a greater degree with hypertensive patients than with their normotensive patients. EH patients, particularly those experiencing emotional distress, appear to have patterns of self-presentation that could present an obstacle to effective communication with their physicians, and this difficulty may be amplified by physicians' disinclination to probe for emotional difficulty. PMID- 1618172 TI - A longitudinal study of the development of anticipatory nausea and vomiting in cancer chemotherapy patients: the role of absorption and autonomic perception. AB - We interviewed 70 cancer patients receiving chemotherapy at home before their second treatment session to obtain baseline measures of absorption, autonomic perception, depression, state-trait anxiety, and basic demographic information. Patients were then interviewed before each of their next six treatment sessions, at which time measures of depression, state anxiety, severity and duration of postchemotherapy nausea and/or vomiting (PCNV), and experience of anticipatory nausea and/or vomiting (ANV) were obtained. Previous findings suggesting that motion sickness, trait anxiety, depression, sex of subject, and age are predictors of the development of ANV were not replicated. Patients with ANV did score significantly higher on measures of absorption and autonomic perception than patients who did not develop ANV. Those variables hypothesized to mediate conditioning (i.e., toxicity of treatment drugs, severity of PCNV, levels of state anxiety) accurately predicted which patients developed ANV. Absorption and autonomic perception added significantly to the prediction. PMID- 1618173 TI - The health belief model and adolescents with insulin-dependent diabetes mellitus. AB - We tested the predictive utility of the health belief model (HBM) for adherence with a complex, ongoing medical regimen in the context of a chronically ill youthful population (56 adolescent outpatients with insulin-dependent diabetes mellitus; mean age = 14 years). A three-construct model of health beliefs was tested: Threat (perceived susceptibility combined with severity), Benefits-Costs, and Cues to seek treatment. Multiple indicators of compliance were used, and metabolic control was measured by glycosylated hemoglobin. The Benefits-Costs and Cues constructs were related to compliance in the theoretically expected positive direction. Threat interacted with Benefits-Costs in the prediction of compliance and with Cues in the prediction of metabolic control. The greatest compliance was achieved with low perceived Threat and high perceived Benefits-Costs. Poor metabolic control was associated with high Threat and Cues. As age increased, adherence to the exercise, injection, and frequency components of the regimen decreased. PMID- 1618174 TI - Correlates of hypoglycemic fear in type I and type II diabetes mellitus. AB - We examined whether fear of hypoglycemia in insulin-dependent diabetes mellitus was associated with (a) higher levels of trait anxiety and general fearfulness, (b) difficulty in differentiating symptoms of anxiety and hypoglycemia, and (c) past experience with hypoglycemia. Joslin Diabetes Center outpatients with Type I and Type II diabetes (N = 232), all requiring insulin, were surveyed. Type I patients experienced significantly more fear of hypoglycemia than Type II patients. For the Type I and Type II groups, higher scores on the Worry subscale of the Hypoglycemia Fear Survey (HFS-W) were associated with higher levels of trait anxiety and fear. Higher scores on the Behavior subscale (HFS-B) were associated with higher levels of fear. Among Type I subjects only, HFS-W scores were also positively associated with past hypoglycemic experience and with difficulty in differentiating anxiety and hypoglycemic symptoms. These latter relations remained significant even after the variance resulting from trait anxiety and fear was removed. Other significant associations with HFS-B scores were not observed. PMID- 1618175 TI - Family/media approach to HIV prevention: results with a home-based, parent-teen video program. AB - We describe the first study with a home-based HIV prevention video program for parents and young teenagers. The objectives of the program are to inform parents and teenagers about the causes and prevention of HIV infection and other sexually transmitted diseases, to increase family problem-solving skills, and to increase teen problem-solving and assertiveness skills. The objectives pertain to the goals of increasing skills needed to help teenagers avoid or manage high-risk behaviors and situations. Forty-five families with at least one 12- to 14-year old were randomly assigned to either experimental (receive video program) or control (no video) conditions in a pretest-posttest design. After 6 months (Follow-Up 1), the experimental and control families were reassessed. The control families next received the video program, and the control families were assessed again (Follow-Up 2). The results indicate increases in parent and teen knowledge and skills only with video viewing. Approaches to improving the video program, particularly with teenagers, are discussed. PMID- 1618176 TI - 3-alkyl GABA and 3-alkylglutamic acid analogues: two new classes of anticonvulsant agents. AB - Recently we showed that 3-alkyl-4-aminobutanoic acids are in vitro activators of brain L-glutamic acid decarboxylase (GAD) that show anticonvulsant activity. Since activation of GAD leads to increased concentrations of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in vitro, these compounds could represent a new class of anticonvulsant agents. Here it is shown that 3 alkylglutamic acid analogues also activate GAD and that all of the compounds in both series are active anticonvulsant agents against low intensity electroshock in mice. The most active compound, 3-isobutyl GABA, was tested further against maximal electroshock in mice and was shown to be very potent after both intravenous and oral administration without causing ataxia. It is not known if brain GABA levels are elevated in vivo by administration of these compounds or if the mechanism of anticonvulsant activity is related to their ability to activate GAD. PMID- 1618178 TI - Characteristics of dorsal and ventral striatal kindling in rats. AB - We examined the characteristics of kindling of seizures with stimulation of the dorsal or ventral striatum in rats. Different groups of rats carried electrodes directed towards the nucleus accumbens or the head, middle, or tail of the caudate. Thresholds for afterdischarge (AD) were high at all sites, and stimulation often produced forced motor responses (motor responses that occurred during the stimulation and were not a consequence of kindling). Kindling at sites in the accumbens proceeded more slowly than at the sites in the caudate, which did not differ among themselves. The duration of accumbens seizures increased dramatically over the course of kindling, whereas the duration of caudate seizures remained relatively short and invariant. Although the kindled seizures resembled seizures kindled from limbic sites, they also contained aspects of seizures triggered from stimulation of the anterior neocortex. We conclude that striatal kindling comprises elements of both limbic and neocortical kindling. PMID- 1618177 TI - Sustained and selective block of IPSPs in brain slices from rats made epileptic by intrahippocampal tetanus toxin. AB - A small dose of tetanus toxin (2-5 ng; 10 mouse LD50) injected into the rat hippocampus produces a chronic epileptic syndrome in which epileptic discharges recur intermittently for 6-8 weeks. Hippocampal slices prepared during this period and maintained in vitro generate both evoked and spontaneous epileptic discharges. The present study used slices prepared 8-18 days after injection of tetanus toxin or vehicle solution into both hippocampi to test whether or not synaptic inhibition was selectively impaired in this experimental epilepsy. Intracellular recordings were made from CA3 pyramidal layer neurones within the tetanus toxin focus, which was identified by field potential recordings of synchronous bursts evoked by afferent stimulation. The intrinsic properties of these neurones did not differ from comparable cells in control-injected rats. All cells generated excitatory postsynaptic potentials (EPSPs) following stimulation of stratum radiatum in CA3. In control slices EPSPs were followed by a 'fast' inhibitory postsynaptic potential (IPSP), peaking at 25-30 ms, with a mean amplitude (+/- SEM) of -6.7 mV (+/- 0.66). In the epileptic slices these were absent, and the EPSP prolonged so that the potential at 30 ms was a depolarisation of +6.6 mV (+/- 2.75). The slow IPSP at 120 ms dropped to -0.27 mV (+/- 0.18) from -3.97 mV (+/- 1.43) (11 cells in each group). The loss of IPSPs cannot be attributed to a shift in reversal potentials in the toxin-injected group because no IPSPs were unmasked by current injection (n = 11). IPSPs also occurred spontaneously in the neurones in control slices, with a mean amplitude of -1.30 mV. Their frequency decreased by a factor of 13 in cells from the chronic focus induced by tetanus toxin (P less than 0.0001, analysis of variance), but their amplitude did not change significantly (mean of -1.22 mV). Spontaneous EPSPs were significantly more frequent and slightly smaller in the toxin-injected group (mean amplitudes 1.35 and 1.13 mV respectively). Together these studies support the hypothesis that the chronically recurring seizures induced by low doses of tetanus toxin can be attributed to a substantial, persistent and selective reduction of inhibitory neurotransmission in the hippocampus. PMID- 1618179 TI - Loreclezole monotherapy in patients with partial seizures. AB - Monotherapy is preferable in the treatment of epilepsy; a new antiepileptic drug has to be checked on its efficacy in monotherapy. In this study patients who had successfully been treated with loreclezole in previous studies were gradually withdrawn from their antiepileptic comedication. Nine patients participated in the study. Reduction of comedication was well tolerated in all, no serious side effects occurred. In 6 patients seizure frequency remained unchanged, i.e., within 50% limits. Two patients experienced a clear increase in seizure frequency. In 2 patients reintroduction of a second antiepileptic drug was mandatory. One patient experienced a further reduction in seizure frequency when monotherapy was reached. This observation indicates efficacy of loreclezole, also in monotherapy. PMID- 1618180 TI - Lamotrigine-induced carbamazepine toxicity: an interaction with carbamazepine 10,11-epoxide. AB - We report an interaction between lamotrigine (LTG), a new antiepileptic drug (AED), and carbamazepine (CBZ) and its primary metabolite CBZ-10,11-epoxide (CBZ E) in 9 consecutive patients (5 male, 4 female, aged 19-31 years). After introduction of LTG (median daily dose 200 mg, range 100-300 mg) the mean serum CBZ-E concentration increased by 45% (P less than 0.01) and the CBZ-E/CBZ ratio increased by 19% (P less than 0.02). In 4 patients these changes were associated with clinical toxicity (dizziness, nausea, diplopia). The possibility of an increase in serum CBZ-E concentrations needs to be considered if toxicity symptoms develop when LTG is added to CBZ therapy. PMID- 1618181 TI - In vitro studies on the broad spectrum anticonvulsant loreclezole in the hippocampus. AB - In hippocampal slices from guinea-pig a paired-pulse stimulation protocol was used to examine the effects of loreclezole, R-(+)-etomidate, phenobarbital and pentobarbital on orthodromic and antidromic GABAergic neuronal inhibition in the CA1 region. All four compounds increased orthodromic GABAergic inhibition, with R (+)-etomidate and pentobarbital inducing a quantitatively larger effect than loreclezole and phenobarbital. Only R-(+)-etomidate and pentobarbital increased antidromic GABAergic inhibition. We propose that all four compounds are anticonvulsant by increasing feed-forward dendritic GABAergic inhibition, whilst only the sedative/hypnotic compounds (R-(+)-etomidate, pentobarbital) increase feedback recurrent GABAergic inhibition. Loreclezole was also shown to inhibit 'low Ca2+' and 'low Mg2+' epileptogenesis at similar concentrations to those active on inhibition. Thus loreclezole may possess other pharmacodynamic properties, beyond its ability to increase feed-forward GABAergic neuronal inhibition, which contribute to its antiepileptic action. PMID- 1618182 TI - Repeated anticonvulsant testing: contingent tolerance to diazepam and clobazam in kindled rats. AB - The acute anticonvulsant efficacy of diazepam (1.5 mg/kg, i.p.) was evaluated by repeated test injection in kindled rats subcutaneously implanted with diazepam filled or empty silastic tubes for 3 weeks. Tolerance developed to acute test injections in both diazepam- and sham-implanted rats. Tolerance developed to a lesser extent in another group of diazepam-implanted rats which did not receive acute intermittent anticonvulsant tests. The hypothesis that contingent tolerance had developed to the anticonvulsant actions of benzodiazepines (diazepam, 1.5 mg/kg, i.p. and clobazam, 10 mg/kg, i.p.) in kindled rats given acute intermittent injections was investigated using a 'before-after' design. Significant contingent tolerance developed in rats which received intermittent benzodiazepine treatment before, but not after, amygdala stimulation. Tolerance developed to different extents depending on the seizure measure evaluated (forelimb clonus duration, amygdala afterdischarge duration, motor seizure latency and duration, and seizure stage). Contingent tolerance to both benzodiazepines developed at a similar rate. The findings suggest that contingent tolerance may contribute a sizeable component to the overall functional benzodiazepine tolerance measured in long-term anticonvulsant drug studies in kindled rats. Several questions regarding contingent tolerance phenomena are posed and the implications of these findings for studies using repeated anticonvulsant testing are discussed. PMID- 1618183 TI - The effect of training on endurance and the cardiovascular responses of individuals with paraplegia during dynamic exercise induced by functional electrical stimulation. AB - Endurance for dynamic exercise, cardiac output, blood pressure, heart rate, ventilation, and oxygen consumption was measured in eight individuals with paraplegia at the end of 4-min bouts of exercise on a friction braked cycle ergometer. Movement of the subjects' legs was induced by electrically stimulating the quadriceps, gluteus maximus and hamstring muscles with a computer-controlled biphasic square--wave current at a frequency of 30 Hz. The friction braked cycle ergometer was pedalled at work rates which varied between 0 and 40 W. Measurements were repeated after 3 and 6 months to assess the affect of training. After 3 months of training it was found that endurance increased from 8 min at a work rate of 0 W to 30 min at a work rate of 40 W. Compared to the cardiovascular responses in non-paralyzed subjects, computerized cycle ergometry was found to be associated with higher relative stresses for a given level of absolute work. Mean blood pressure, for example, increased by over 30% during maximal work in individuals with paralysis compared to the typical response obtained for able bodied subjects. Analysis of the data showed that instead of the 20-30% metabolic efficiency commonly reported for cycle ergometry, the calculated metabolic efficiency during computer-controlled cycle ergometry was only 3.6%. PMID- 1618184 TI - Oxygen delivery does not limit peak running speed during incremental downhill running to exhaustion. AB - Oxygen consumption (VO2), ventilation (VI), respiratory exchange ratio (R), stride frequency and blood lactate concentrations were measured continuously in nine trained athletes during two continuous incremental treadmill runs to exhaustion on gradients of either 0 degree or -3 degrees. Compared to the run at 0 degree gradient, the athletes reached significantly higher maximal treadmill velocities but significantly lower VO2, VI, R and peak blood lactate concentrations (P less than 0.001) during downhill running. These lower VO2 and blood lactate concentrations at exhaustion indicated that factors other than oxygen delivery limited maximal performance during the downhill run. In contrast, stride frequencies were similar at each treadmill velocity; the higher maximal speed during the downhill run was achieved with a significantly longer stride length (P less than 0.001); maximal stride frequency was the same between tests. Equivalent maximal stride frequencies suggested that factors determining the rate of lower limb stride recovery may have limited maximal running speed during downhill running and, possibly, also during horizontal running. PMID- 1618185 TI - Effects of training on iron status in cross-country skiers. AB - Haematological changes were studied in cross-country skiers during a 33-week training season (7 h a week). The daily amounts of training were calculated from the duration and the intensity of the exercise and then used to estimate training responses associated with a first order transfer function. The profile of system training responses (STR) was determined by convolution between the amounts of training and a first-order transfer function. Linear regressions were used to determine correlation coefficients between STR and iron status indices. Among the values for the time constants of decay, the one giving the best fit between STR and iron status indices was chosen. A relationship was noted between on the one hand STR and changes in serum ferritin concentration ([FERR]) and on the other hand STR and change in mean cell volume (MCV). The [FERR] was decreased and MCV was increased by training. It is suggested that a decrease in [FERR] could have been related to a decrease in total body iron stores. However, large and rapid changes in [FERR] could not have been a reflection of changes in total body iron stores. Equilibrium between [FERR] and total body iron stores could have been temporarily altered by the effects of training. Moreover, iron stores did not seem to have been sufficiently depleted to restrict erythropoiesis. The MCV increased slightly in response to intense training suggesting that training enhances the proportion of young erythrocytes. PMID- 1618186 TI - Thermoregulatory stress during rest and exercise in heat in patients with a spinal cord injury. AB - Twelve subjects with spinal cord injuries and four controls (all male) were exposed to heat while sitting at rest or working at each of three environmental temperatures, 30, 35 and 40 degrees C, with a relative humidity of 50%. Exercise was accomplished at a load of 50 W on a friction-braked cycle ergometer which was armcranked or pedalled. Functional electrical stimulation of the legs was provided to the subjects with quadriplegia and paraplegia to allow them to pedal a cycle ergometer. The data showed that individuals with quadriplegia had the poorest tolerance for heat. As an example, in this group, accomplishing armcrank ergometry while working at an environmental temperature of 40 degrees C resulted in an increase in aural temperature of 2 degrees C in 30 min. The aural temperature of individuals with paraplegia working for the same length of time under the same conditions rose approximately 1 degree C. There was virtually no change in the aural temperature in the control subjects. PMID- 1618187 TI - Aerobic endurance, anatomical factors and time properties of laser Doppler recorded skin postocclusive hyperaemia. AB - Aerobic endurance capacity is partly dependent on blood supply to and metabolic capacity of the active muscles. Recordings of lower limb skin postocclusive hyperaemia with laser Doppler flowmetry can differentiate between patients with lower limb atherosclerosis and healthy controls. In this study, we investigated the relationship between aerobic endurance, calf volume, common femoral artery diameter and time properties of the postocclusive laser Doppler curve. A group of 16 healthy male subjects with values for aerobic endurance which varied from those of untrained men to elite endurance trained athletes were examined. Duration of laser Doppler recorded skin postocclusive hyperaemia was significantly correlated to both aerobic power and anaerobic threshold (P less than 0.01). Hyperaemia in subjects with large common femoral artery diameter was of shorter duration (P less than 0.05). The peak and mean body mass related blood flow during hyperaemia was correlated to anaerobic threshold (P less than 0.05). These results were in agreement with previous studies indicating an effect of endurance training on the blood supply to the muscles concerned. PMID- 1618188 TI - Studies on the immediate and delayed leucocytosis elicited by brief (30-min) strenuous exercise. AB - Eight healthy male volunteers exercised for two 30-min sessions starting 3 h apart on an electronically braked cycle ergometer at a work load (mean 155.9 W, SD 33.4 W) which required an oxygen consumption that was 70% of their maximal rate of oxygen uptake. Venous blood samples were taken through an indwelling cannula over a period of 6 h beginning shortly before the first bout of exercise and were analysed for routine haematological parameters and for lactate, noradrenaline, adrenaline and cortisol. Both bouts of exercise induced an immediate leucocytosis due to rises in lymphocytes and neutrophils but only the first exercise bout induced a substantial delayed neutrophilia. In at least five subjects, changes in lymphocyte and platelet numbers were correlated (Spearman's rank procedure, P less than 0.05) with simultaneous changes in the plasma concentrations of lactate, noradrenaline and adrenaline over the 6-h period studied. Increases in the plasma concentration of cortisol due to exercise correlated positively with the percentage changes in neutrophil numbers at 3 h and 6 h. These results are consistent with the suggestion that the immediate and delayed leucocytosis induced by exercise are mediated respectively by catecholamine and by cortisol. PMID- 1618189 TI - Changes in the leucocyte count during and after brief intense exercise. AB - Twelve healthy male volunteers exercised at 200 W on a cycle ergometer for 8 min or until exhausted, if sooner. Retrospectively, subjects fell into two groups. During the last minute of exercise at 200 W, those in group 1 (n = 5) had a mean respiratory exchange ratio (R) of 1.06 (SD 0.01) and were working at a mean of 79% (SD 4%) of their maximum oxygen consumption (VO2max) as measured in a separate incremental load test. For subjects in group 2 (n = 7), R was 1.31 (SD 0.08) and their VO2 was maximal (mean 101%. SD 3%). Plasma lactate, and adrenaline concentrations rose to higher levels during exercise in subjects in group 2 than in those in group 1. At the finish of exercise, the leucocyte count and the plasma lactate concentration immediately began to fall in subjects in group 1 whereas in group 2 subjects both rose for several minutes before falling. Plasma catecholamine concentrations fell rapidly in both groups during recovery. PMID- 1618191 TI - Phosphorus-31 magnetic resonance spectroscopy of forearm flexor muscles in student rowers using an exercise protocol adjusted for differences in cross sectional muscle area. AB - To assess exercise energy metabolism of forearm flexor muscles in rowers, six male student rowers and six control subjects matched for age and sex were studied using phosphorus-31 magnetic resonance spectroscopy (31P-MRS). Firstly, to adjust for the effect of differences in cross-sectional muscle area, the maximal cross sectional area (CSAmax) of the forearm flexor muscles was estimated in each individual using magnetic resonance imaging. Multistage exercise was then carried out with an initial energy production of 1 J.cm-2 CSAmax for 1 min and an increment of 1 J.cm-2 CSAmax every minute to the point of muscle exhaustion. A series of measurements of 31P-MRS were performed every minute. The CSAmax was significantly greater in the student rowers than in the control subjects [19.8 (SD 2.2) vs 17.1 (SD 1.2) cm2, P less than 0.05]. The absolute maximal exercise intensity (J.min-1) was greater in the rowers than in the control subjects. However, the maximal exercise intensity per unit of muscle cross sectional area (J.min-1.cm-2) was not significantly different between the two groups. During mild to moderate exercise intensities, a decrease in phosphocreatine and an increase in inorganic phosphate before the onset of acidosis were significantly less in the rowers, indicating a requirement of less adenosine 5'-diphosphate to drive adenosine 5'-triphosphate production. The onset of acidosis was also significantly delayed in the rowers. No difference was observed in forearm blood flow between the two groups at the same exercise intensity (J.min-1.cm 2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618190 TI - Exogenous carbohydrate oxidation from maltose and glucose ingested during prolonged exercise. AB - Intestinal perfusion studies have shown that glucose absorption from maltose occurs faster than from isocaloric glucose. To determine whether ingested maltose might be a superior source of carbohydrate (CHO) for endurance athletes, we compared the rates of gastric emptying, absorption and oxidation of 15 g.100 ml-1 solutions of maltose and glucose. Six endurance-trained cyclists drank 1200 ml of either U-14C maltose or U-14C glucose as a 400-ml loading bolus immediately before exercise, and as 8 x 100-ml drinks at 10-min intervals during a 90-min ride at 70% of maximal oxygen consumption. The rates of gastric emptying [maltose 690 (SD 119) ml.90 min-1; glucose 655 (SD 93) ml.90 min-1], the appearance of U 14C label in the plasma, and the peak rates of exogenous CHO oxidation [maltose 1.0 (SD 0.09) g.min-1; glucose 0.9 (SD 0.09) g.min-1] were not significantly different. Further, the 51 (SD 8) g of maltose and the 49 (SD 9) g of glucose oxidised during exercise were similar. Each accounted for approximately 20% of the total CHO oxidised during the 90 min of exercise. Since only half of the CHO delivered to the intestine was oxidised in the 90-min ride (maltose 49%; glucose 50%), we conclude that neither the rate of gastric emptying, nor digestion limited the rate of ingested CHO utilisation during the early stages of exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618192 TI - Relationship between record time and maximal oxygen consumption in middle distance running. AB - The relationship between record time (tr) and maximal oxygen uptake (VO2max) has been examined in 69 male physical education students who had taken part in 800-m and 1500-m footraces. It was found that tr and VO2max were inversely related. The relationships tr = f(VO2max) have been fitted by two exponential equations: tr (1500 m) = 698e-0.0145VO2max; tr (800 m) = 272e-0.011VO2max; P less than 0.001. A mathematical formulation of the energy conservation principle in supramaximal running, based on the exponential increase of the oxygen uptake as a function of time with a rate constant of 0.025 s-1 has been applied to the tr calculation from VO2max. As calculated tr were highly correlated to measured tr (P less than 0.001), it was concluded that the relationships tr = f(VO2max) can be interpreted on the basis of the model described in this study. PMID- 1618193 TI - Age-specific correlation analysis of longitudinal physical fitness levels in men. AB - This study investigated the age-specific tracking of adult health- and performance-related fitness scores. In addition, the independent contribution of adolescent physical characteristics to the explanation of adult fitness scores was also studied. The sample consisted of 173 adults observed at age 30 years. These subjects had been followed at annual intervals from age 13 to age 18 years and were remeasured at age 30 years. At each age nine fitness tests were administered together with the recording of anthropometric dimensions, biological maturation, sports participation and family characteristics. Tracking was measured by the inter-age correlations at each age between 13 and 18 years and the performance scores at 30 years. The independent contribution of characteristics observed during adolescence to the explanation of adult fitness was investigated through stepwise multiple regression analysis and discriminant analysis with the adult fitness scores as the dependent variables and the fitness, maturation, anthropometric characteristics, sports participation and family background as the independent variables. Tracking between age 13 and age 30 years was moderately high (46% of variance explained) for flexibility, low to moderate (between 19% and 27% of variance explained) for the other fitness parameters and low for pulse recovery and static strength (7% to 11% of variance explained). Between age 18 and age 30 years the tracking was high for flexibility, moderately high for explosive and static strength, and moderate for the other fitness parameters except for pulse recovery. The amount of variance of adult fitness levels explained increased significantly when other characteristics observed during adolescence entered the regressions or discriminant functions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618194 TI - Aerobic capacity of forestry workers and physical demands of forestry operations. AB - The present study aimed at evaluating the aerobic capacities of forestry workers and the physical demands of their occupation. A submaximal cycle ergometer test was conducted on 22 male forestry workers and 15 male sedentary office workers aged 40-59 years. The slope of the regression line of heart rates on given exercise intensities was significantly smaller in the forestry workers than in the office workers. The mean heart rate of the forestry workers was 9 beats.min-1 less than that of the office workers at the initial exercise intensity of 50 W. This difference increased to 25 beats.min-1 at 175 W. For 6 of the 22 forestry workers, heart rates were recorded continuously during a usual workday. The metabolic rates, as multiples of basal metabolic rate (in met) of various forestry activities were estimated from the average heart rate during the activity of interest and a predicted maximal oxygen consumption of the subject obtained from a submaximal cycle ergometer test. The mean energy expenditure was 4.5 met with a range of 3.3-6.3 met for an average of 509 min at a worksite. These results indicated that the forestry workers had high aerobic capacities and this was ascribed to the high physical demands of their occupation. PMID- 1618195 TI - Oxygen availability and motor unit activity in humans. AB - Six men were studied to determine the interrelationships among blood supply, motor unit (MU) activity and lactate concentrations during intermittent isometric contractions of the hand grip muscles. The subjects performed repeated contractions at 20% of maximal voluntary contraction (MVC) for 2 s followed by 2 s rest for 4 min with either unhindered blood circulation or arterial occlusion given between the 1st and 2nd min. The simultaneously recorded intramuscular MU spikes and surface electromyogram (EMG) data indicated that mean MU spike amplitude, firing frequency and the parameters of surface EMG power spectra (mean power frequency and root mean square amplitude) remained constant during the experiment with unhindered circulation, providing no electrophysiological signs of muscle fatigue. Significant increases in mean MU spike amplitude and frequency were, however, evident during the contractions with arterial occlusion. Similar patterns of significant changes in the surface EMG spectra parameters and venous lactate concentration were also observed, while the integrated force-time curves remained constant. These data would suggest that the metabolic state of the active muscles may have played an important role in the regulation of MU recruitment and rate coding patterns during exercise. PMID- 1618196 TI - Changes in the concentrations of Na+, K+ and Cl- in secretion from the skin during progressive increase in exercise intensity. AB - A simple method for sampling skin secretion in 1-min periods was developed for investigating the effects of progressive increases in exercise intensity on Na+, K+ and Cl- secretions from the skin of the forearm. Ten healthy male subjects performed exercise consisting of eight stepwise increases in intensity from 50 to 225 W, with a 25-W increase at each step. Exercise at each step was for 3 min followed by a 1-min recovery period. Samples of blood and skin secretion were taken during the recovery period. Significant positive correlations were found between the mean concentrations of Na+ and Cl- and between those of K+ and Cl- in the skin secretion. The concentrations of electrolytes in the skin secretion also showed significant correlations with the blood lactate concentrations. The inflection points for secretions of Na+, K+ and Cl- were 4.04, 3.61 and 3.83 mmol.l-1 of blood lactate; 64.42, 61.96 and 62.14% of maximal oxygen consumption (VO2max); and exercise intensities of 123.01, 117.65 and 125.07 W, respectively. No significant differences were observed between the value of 67.27% of VO2max or 134.00W at the onset of blood lactate accumulation (OBLA) and the inflection points. From these results we concluded that changes in electrolyte concentrations in skin secretion during incremental exercise according to this protocol were closely related with the change in the blood lactate concentration, and that the inflection points for electrolytes may have been near the exercise intensity at OBLA. PMID- 1618197 TI - Acute myocardial infarction (AMI) in Finland--baseline data from the FINMONICA AMI register in 1983-1985. AB - The acute myocardial infarction (AMI) register of the FINMONICA study, the Finnish part of the WHO-coordinated multinational MONICA project, operates in the provinces of North Karelia and Kuopio in eastern Finland and in Turku, Loimaa and in communities around Loimaa in southwestern Finland. The AMI register serves as an instrument for the assessment of trends in mortality from coronary heart disease (CHD) and of the incidence and attack rates of AMI among 25-64-year-old residents of the study areas. This report describes the methods used in the FINMONICA AMI register and the findings during the first 3 years of the study, in 1983-1985. The criteria of the multinational WHO MONICA project were used in the classification of fatal events and in the diagnosis of non-fatal definite AMI, but based on the experience within the FINMONICA study, stricter diagnostic criteria than those originally described in the WHO MONICA protocol were used for non-fatal possible AMI. This led to a marked improvement in the comparability of the data from the three study areas with regard to the incidence and attack rates of non-fatal AMI. During the 3-year period the total number of registered events was 6266 among men and 2092 among women. Among men the incidence and attack rates of AMI and mortality from CHD were higher in eastern than in southwestern Finland. Also among women the incidence and attack rates of AMI were higher in eastern than in southwestern Finland, whereas there was no regional difference in mortality from CHD among women. The mortality findings of the FINMONICA AMI Register were in good agreement with the official CHD mortality statistics of Finland. PMID- 1618198 TI - Incidence of heart failure in eastern Finland: a population-based surveillance study. AB - Heart failure is a frequent disorder, but there is little population-based data available on its incidence. We have studied the incidence of heart failure in 45 74-year-old inhabitants in four rural communities in eastern Finland (total population 37,600; 11,000 45-74 years of age). The aim was to identify all patients in whom symptoms had started and in whom a diagnosis of heart failure had been established during a 2-year study period. General physicians, working in community health centres in the study area, referred all their patients with suspected heart failure to the study. A register of drug reimbursement, hospital discharge and other health care registers were used to identify patients who had not been referred. The Boston criteria were used to verify the diagnosis. One hundred and thirteen subjects (51 men and 62 women) were enrolled, of whom 51 (38 men and 13 women) had definite heart failure. Age-adjusted incidence rate of heart failure (per 1000 . year-1) was 4.0 in men and 1.0 in women, and the incidence rates increased with age in both sexes. Coronary heart disease or hypertension was evident in 41 (80%) cases. The striking difference in the incidence rates between men and women is probably explained by the excessive occurrence of coronary heart disease among men in eastern Finland. PMID- 1618199 TI - Morning peak in the incidence of myocardial infarction: experience in the ISIS-2 trial. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. AB - To investigate the circadian pattern of acute myocardial infarction (MI) in a large international patient population, the time of day of the onset of symptoms was prospectively determined in 12,163 consecutive patients randomized in the ISIS-2 Trial (Second International Study of Infarct Survival). Overall, there was a marked circadian variation (P less than 0.001) in the incidence of MI characterized by a sharp increase from 0600 h to 0800 h, with a peak period from 0800 h to 1100 h followed by a gradual decline from 1100 h to 1800 h. During the evening and night there was a steady trough, with no evidence of a second peak. Although there was some scatter, this circadian pattern was similar among patients of five different geographic regions on three continents and in various subcategories of patients defined with respect to age, gender, previous MI, and aspirin intake prior to MI. The circadian pattern of diabetics, however, was different compared with non-diabetics (P less than 0.005, adjusted less than 0.01), and it demonstrated no significant variation. This increased morning incidence of MI indicates specific triggering mechanisms that are particularly likely to occur during, or just before, that time of day. Further investigation of physiological changes during the day is needed to identify any such triggers of MI and so perhaps to aid in improving preventive strategies of the disease. PMID- 1618201 TI - The accuracy of decision-making of a semi-automatic defibrillator during cardiac arrest. AB - The accuracy of decision-making of a semi-automatic defibrillator was assessed at 57 cardiac arrests in 55 patients. The initial rhythm was ventricular fibrillation at 40 arrests and was correctly identified in 37 (sensitivity 92.5%). In the other 17 arrests initial rhythms were not ventricular fibrillation and 16 were correctly identified (specificity 94%). Continuous electrocardiographic recordings of the arrests were analysed in 8-12 s segments: of 432 segments showing ventricular fibrillation, 352 were correctly identified (sensitivity 81%); 3895 of 4139 segments showing rhythms other than ventricular fibrillation were correctly identified (specificity 94%). The percentage accuracy of detection of ventricular fibrillation varied from 0-100% (mean 91%) and for non-ventricular fibrillation from 51-100% (mean 92%). When 104 segments of ventricular fibrillation and 470 segments of non-ventricular fibrillation with cardiopulmonary resuscitation artefact were excluded from the analysis, a sensitivity of 91% and specificity of 96% were obtained. Thus the detection of cardiac arrest rhythms using a microprocessor based detection system for patients with cardiac arrest has a high sensitivity for ventricular fibrillation and specificity for non-ventricular fibrillation. PMID- 1618200 TI - Late potentials after acute myocardial infarction. Performance of different criteria for the prediction of arrhythmic complications. AB - In order to compare different criteria for the definition of late potentials in patients after myocardial infarction, three signal averaged ECG variables, duration of the signal-averaged QRS complex (QRS), root-mean-square voltage of the terminal 40 ms (RMS-40), and the duration of low amplitude signals less than 40 microV (LASD-40), were assessed in 332 survivors of acute myocardial infarction who were followed-up for at least 6 months, during which 12 patients died suddenly and 14 suffered symptomatic sustained ventricular tachycardia. The associations of the three variables with arrhythmic events were analysed in the total population, in infarct site and age-specific subgroups. The sensitivity and specificity for the prediction of arrhythmic events was computed (for all dichotomy points) and compared with nine published criteria for late potentials based on the same three variables. Analysis showed that (a) the total signal averaged QRS duration was a better predictor of arrhythmic events than the other two variables, (b) for arrhythmic events in cases of anterior infarctions, higher RMS-40 dichotomy limits and lower QRS and LASD-40 dichotomy limits were needed for cases of inferior infarction, (c) a multivariate stratification of arrhythmic events based on all three variables performed better in the anterior infarction population than in the inferior infarction population, (d) the strategy defining late potentials, which requires that two variables reach critical values, is better than the strategies that require that any one or all three variables reach critical values, (e) all the definitions of late potentials performed differently in the populations with anterior as compared to inferior infarctions; to identify groups at similar risk of arrhythmic events, different criteria defining late potentials should be used in these subpopulations. PMID- 1618202 TI - Magnetocardiographic non-invasive localization of accessory pathways in the Wolff Parkinson-White syndrome by a multichannel system. AB - Electrical activity can be localized by magnetocardiography (MCG) non-invasively. In this study a 37-SQUID (Super Conducting Quantum Interference Device) sensor multi-channel system (KRENIKON) was used to assess the potential of magnetocardiography to localize accessory pathways with a multichannel system. Seven WPW patients were studied by means of magnetocardiography. Prior to the MCG recordings, the site of the accessory pathway had been determined in all patients by invasive catheter mapping. MR images of the heart were used for anatomical correlation. The magnetocardiographic localization of the accessory pathway corresponded with catheter mapping within 2.1 cm on average (total range: 0-5 cm). This is thus, a promising new method for non-invasive localization of accessory pathways in WPW patients. PMID- 1618203 TI - Amyloid cardiomyopathy in systemic non-hereditary amyloidosis. Clinical, echocardiographic and electrocardiographic findings in 30 patients with AA and 24 patients with AL amyloidosis. AB - To underline the role of echocardiography in the detection of cardiac involvement in patients with amyloidosis, physical examination, echocardiography and electrocardiography were performed in 30 patients with AA amyloidosis (amyloid protein A, associated with chronic inflammatory disease, usually without cardiomyopathy) and 24 patients with AL amyloidosis (the immunoglobulin light chain derived type, often associated with cardiomyopathy). All patients had histological confirmation of amyloidosis by rectal or subcutaneous abdominal fat biopsy. The combination of increased thickness of the left ventricular posterior wall and interventricular septum with a low voltage electrocardiographic pattern is highly specific for cardiac amyloidosis and was found in 3/30 (10%) of the AA patients and in 13/24 (54%) of the AL patients. The echocardiographic abnormalities were strongly related to the degree of clinical heart disease, showing mildly or moderately increased wall thickness in the early asymptomatic phase or severe thickening and hypokinesia of the left ventricular posterior wall and interventricular septum in clinically apparent cardiac dysfunction. Echocardiography appears to be a sensitive test for the detection of cardiac involvement in amyloidosis, in symptomatic as well as asymptomatic patients. PMID- 1618204 TI - Epidural spinal electrical stimulation for severe angina: a study of its effects on symptoms, exercise tolerance and degree of ischaemia. AB - The effectiveness of epidural spinal electrical stimulation has been studied in 14 patients with severe intractable angina unresponsive to standard therapies including bypass grafting. After implantation of the neurostimulator units the patients were assessed by a symptom questionnaire, treadmill exercise testing and right atrial pacing. There was a significant improvement of symptoms and GTN consumption fell markedly. With the neurostimulator on, exercise duration increased from a mean (CI) of 414 (153) to 478 (149) s, and total ST segment depression was less both at maximum exercise (7.1 (4.5) vs 5.6 (4.2) mm) and at 90% of the maximum control heart rate (3.5 (3.7) vs 2.6 (4.3) mm), with similar rate-pressure product at maximum exercise. With right atrial pacing the maximum heart rate reached before onset of angina was increased (143 (14) to 150 (7) b.min-1) and total ST segment depression was less at all heart rates. Benefit has persisted in some patients for over 2 years without any apparent adverse sequelae. Epidural spinal electrical stimulation is, therefore, an alternative therapy for some patients with intractable angina which has not responded to standard therapies. PMID- 1618205 TI - Electrocardiographic changes associated with haematocrit variations. AB - The electrical resistivity of intracardiac blood is less than the resistivity of the surrounding tissues. This affects the transmission of cardiac forces to the body surface: the radial forces are enhanced, whereas the transmission of tangential forces is diminished (the Brody effect). Blood resistivity is directly related to haematocrit, hence, haematocrit changes are expected to affect the transmission of cardiac forces, resulting in changes in QRS complex voltage. To assess this hypothesis, a 12-lead electrocardiogram was recorded in 40 patients affected by thalassaemia before and after a transfusion of concentrated red cells. The voltage of each QRS component was carefully measured in every lead, and the sum of all R wave amplitudes (sigma R) was calculated. The post transfusional electrocardiogram reflected a significant decrease in the R wave amplitude in every lead. sigma R also decreased, whereas S wave amplitude in lead V6 increased. A negative correlation between the ratio of haematocrit pre/post transfusion and that of the corresponding sigma R values was also observed (r = 0.434; P less than 0.01). An increase in haematocrit is therefore associated with a decrease in R wave amplitude. These findings explain why several patients with high haematocrit manifest relatively low voltage QRS complexes. PMID- 1618206 TI - M-mode, 2-D and Doppler echocardiographic study in 65 patients with Behcet's syndrome. AB - The cardiac involvement in Behcet's syndrome in sixty-five patients (mean disease duration 5.7 +/- 4.1 SD years) was studied, in comparison with 70 healthy, age- and sex-matched controls. The electrocardiograms, chest radiographs and M-mode, 2 D and Doppler echocardiography were evaluated in a blind protocol. There were no significant differences in the prevalence of cardiac findings between the probands and the controls. It is concluded that cardiac involvement in Behcet's syndrome occurs only sporadically. PMID- 1618207 TI - Doppler echocardiographic observations of diastolic trans-septal flow through small ventricular septal defects. AB - Turbulent left-to-right trans-septal diastolic blood flow with a peak velocity greater than 0.5 m.s-1 was detected by pulsed Doppler echocardiography in 10 out of 204 (4.9%) children with isolated small ventricular septal defects. For children older than 10 years, it was observed in over a quarter of cases (27%). Peak diastolic velocities ranged from 0.6-1.9 m.s-1 (mean 1.2 m.s-1) and in all patients the duration of diastolic flow exceeded that of the systolic trans septal jet. Three different patterns of diastolic flow were observed and in eight cases pre-systolic acceleration was present. Turbulent diastolic flow across small ventricular septal defects is a common finding in older children and should not be confused with other causes of disturbed diastolic flow within the right ventricle. PMID- 1618208 TI - Evaluation of changes in myocardial function on exercise in patients with coronary artery disease using gated MIBI scintigraphy. AB - Technetium-99m-methoxy-isobutyl-isonitrile (MIBI) is a myocardial perfusion agent which allows simultaneous assessment of left ventricular function. We evaluated left ventricular (LV) function with exercise using a new method of myocardial profiling in 43 patients with chest pain. Twenty-eight had significant coronary artery disease and 15 were normal on coronary angiography. Results were compared to equilibrium radionuclide ventriculography. MIBI fractional shortening (FS) correlated well with ejection fraction (EF) on exercise (r = 0.79, P = less than 0.001). There was also a good correlation between changes in global function from rest to exercise (r = 0.82, P = less than 0.001) with a sensitivity of diagnosing CAD of 71% and specificity of 80%. New regional wall abnormalities were detected in 25/28 with CAD with a sensitivity of 89% and specificity of 60%. There was also a close correlation between mean diameters measured with gated MIBI scans and volumes measured with RNV, end-diastolic diameter (EDD) versus end-diastolic volume (EDV) r = 0.78 (P = less than 0.001) at rest and r = 0.74 (P = less than 0.001) on exercise and end-systolic diameter (ESD) versus end-systolic volume (ESV) r = 0.72 (P = less than 0.001) at rest and r = 0.72 (P = less than 0.001) on exercise. This produced a sensitivity for detecting CAD of 79% and a specificity of 73%. These results show that gated MIBI scanning on exercise provides information comparable to RNV so enhancing the diagnostic usefulness of MIBI. PMID- 1618209 TI - A prospective study on percutaneous coronary angioscopy with different guiding techniques in patients with coronary heart disease. AB - The technical success of percutaneous coronary angioscopy using different guiding techniques was evaluated in 17 patients before (n = 17) and after (n = 8) coronary angioplasty. Steering the angioscope along or over a guidewire was successful in both groups; failures were predominantly due to insufficient alignment of the angioscope using along-the-wire guiding. Although over-the-wire angioscopy promises superior guiding and alignment capabilities, several technical problems remain unsolved. PMID- 1618210 TI - Sudden death from pulmonary thromboembolism: chronobiological aspects. AB - The aim of this study was to determine whether sudden cardiac death from pulmonary embolism exhibits any chronobiological rhythm. Five hundred and seven consecutive subjects dying suddenly outside of hospital and brought into our Emergency Department from January 1983 to December 1989 were studied. The time and date of event were accurately recorded. All subjects underwent autopsy and 48 of them were found to have died of pulmonary embolism (23 males, mean age 73.9 +/ 8 years and 25 females, mean age 76 +/- 12 years). All data were analysed by means of single cosinor[19,20]. In the subjects with pulmonary emboli both a circadian and a circannual rhythmicity were found, with a significant acrophase respectively in the morning (h.min. 11.46, P = 0.003) and in winter (-19.3, P = 0.009). PMID- 1618211 TI - Prevalence of transient myocardial ischaemia during the first year after a myocardial infarction. Effect of treatment with verapamil. The Danish Study Group on Verapamil in Myocardial Infarction. AB - DAVIT-II is a double-blind, randomized, multicentre, placebo-controlled study of long-term treatment with verapamil 360 mg per day administered to patients who have suffered an acute myocardial infarction (AMI). In the present study, comprising a subset of DAVIT-II, 48 h continuous ECG recordings demonstrated transient ST segment deviation indicative of myocardial ischaemia after one week, prior to randomization, in 18% (10 of 57) of the patients. After one month, 24% (11 of 46) of the placebo and 8% (3 of 39) of the verapamil-treated patients (P = 0.04) had myocardial ischaemia; after one year the figures were 26% (9 of 35) and 4% (1 of 27) (P = 0.02), respectively. At 18 months the 'major' event rate in patients who had had ischaemia before randomization was 40% and 23.8% in patients without ischaemia (P = 0.057). In the placebo group, 63% of 91 episodes of ST depression were recorded between 0600 h and 1800 h, and 62% of 26 episodes of ST elevation between 1800 h and 0600 h (P less than 0.001). Nine episodes of ST depression and no episode of ST elevation were recorded in the verapamil-treated patients. In conclusion, 20-25% of post-AMI patients have transient ischaemia; verapamil prevents ischaemia, and a pronounced circadian variation of ST segment deviations can be demonstrated. PMID- 1618212 TI - Efficacy, safety and duration of nitrate-free interval to prevent tolerance to transdermal nitroglycerin in effort angina. AB - The magnitude of tolerance to the anti-anginal efficacy of transdermal nitroglycerin and the efficacy and safety of short (4 h) and long (10 h) nitrate free intervals for its prevention, were investigated in a randomized, double blind, placebo-controlled crossover trial of 4 week-long treatment regimens: placebo, continuous therapy with a 50 mg patch (10 mg.24 h-1), and 4 h and 10 h nitrate-free periods. Only patients showing greater than 1 min increase in time to 1 mm ST depression after acute patch administration were eligible. Twelve men completed the study. One other anti-anginal medication (a beta-blocker in nine and calcium antagonist in two) was permitted in a constant dose throughout the study. Patients underwent exercise testing on days 1 and 7 of each treatment period, and 24 h ambulatory ECG monitoring on day 6. Compared to placebo, transdermal nitroglycerin on day 1 significantly improved time to 1 mm ST depression by 35%, and time to angina, exercise duration and maximal workload by 21%, 13% and 9% respectively. These improvements were totally lost after 7 days' continuous therapy, but completely maintained by a 10 h nitrate-free period (improvements of 35%, 25%, 16% and 11% respectively) but not by a 4 h nitrate free period (non-significant improvements of 15%, 2%, 4% and 1% respectively). The differences between 10 and 4 h nitrate-free were significant for each end point. Neither duration of ambulatory ischaemia, nor the proportion of patients experiencing greater than or equal to 5 min ischaemia during the scheduled nitrate-free interval differed between treatments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618213 TI - Transluminal implantation of artificial heart valves. Description of a new expandable aortic valve and initial results with implantation by catheter technique in closed chest pigs. AB - A new artificial aortic valve prosthesis was developed for implantation by the transluminal catheter technique without thoracotomy or extracorporal circulation. The new heart valve was prepared by mounting a porcine aortic valve into an expandable stent. Before implantation, the stent-valve was mounted on a balloon catheter and compressed around the deflated balloon. The stent-valve mounted balloon catheter was then advanced retrogradely to the ascending aorta or the aortic root in anaesthetized pigs. Implantation was performed by balloon inflation which expanded the stent-valve to a diameter exceeding the internal diameter of the vessel--thus ensuring a stable fixation against the vessel wall. A total of nine implantations were performed in seven 70 kg closed chest pigs. Sub- and supracoronary implantation was performed in two and three pigs, respectively, while implantation in both positions was done in two. Angiographic and haemodynamic evaluation after implantation revealed no significant stenosis (less than or equal to 16 mmHg) in any of the nine valves and trivial regurgitation in only two. Complications were associated with restriction of the coronary blood flow in three animals. This preliminary study indicates that artificial aortic valves can be implanted in closed chest animals by transluminal catheter technique. PMID- 1618214 TI - Histopathological findings in three children with His bundle tachycardia occurring subsequent to cardiac surgery. AB - This report concerns three children with His bundle tachycardia who died following cardiac surgery. At autopsy the conduction system was examined in detail. In all three, the sinus node was intact and supplied by a well-formed artery. Haemorrhagic tracks were identified invading the penetrating atrioventricular bundle. The tracks originated from stitches placed close to the conduction tissue. The hypothesis that disruption of the conduction tissue results in an arrhythmogenic focus is discussed. PMID- 1618215 TI - Acquired aorto-pulmonary fistula in acute dissection. AB - We describe a 41-year-old man with an acute dissection of the ascending aorta with fistulation into the pulmonary artery. The diagnosis was made pre operatively by 2-D and Doppler echocardiography. Surgery was successfully performed. PMID- 1618216 TI - Pleural effusion following coronary perforation during balloon angioplasty: an unusual presentation of the postpericardiotomy syndrome. AB - We report on the development of features of the postpericardiotomy syndrome following coronary perforation during balloon angioplasty, in a patient that was managed conservatively. The case illustrates that while cardiac tamponade does not invariably follow coronary perforation, late consequences derived from this complication may occur. It also widens the spectrum of conditions where the postpericardiotomy syndrome has been observed. PMID- 1618217 TI - Mesothelioma of the atrioventricular node: first successful follow-up after excision. AB - Mesothelioma of atrioventricular nodes may cause congenital heart block and diagnosis is usually confirmed at post-mortem. Awareness of the possibility of the development of this tumour and selective coronary arteriography may help to diagnose this in life. PMID- 1618218 TI - Differences in the antiischaemic effects of molsidomine and isosorbide dinitrate. PMID- 1618219 TI - The future of gynaecological oncology in Spain. PMID- 1618220 TI - The influence of initial residual disease on the outcome of second-look laparotomy in patients with carcinoma of the ovary. AB - Sixty four patients with epithelial ovarian cancer underwent second-look laparotomy. Influencing factors on the outcome of the second-look laparotomy were analysed. Both grade and stage appeared to have an effect on the outcome of the procedure. However, this effect appeared to be dependent on the amount of residual disease after primary surgery. The amount of residual disease appeared to be independently associated with the outcome of second-look laparotomy. PMID- 1618221 TI - Endometrioid carcinoma arising in endometriosis. Case report. AB - Malignant transformation arising in endometriosis has been reported in some cases. Following Sampson's criteria, about 0.7%-1% of all cases of endometriosis undergo malignant transformation and the ovary is the most frequent site. A case is reported of a patient with endometriosis which, after 10 years, grew into ovarian endometrioid carcinoma. The relationship between endometriosis and cancer suggests a radical treatment of endometriosis and a careful assessment of postmenopausal woman presenting reactivation signs. PMID- 1618222 TI - Uterine cervix carcinoma. Histological radiation response (H.R.R.). AB - As most Carcinoma of the Uterine Cervix (CUC) has been found at advanced stages, Radiotherapy (RT) is still the most important treatment. Unfortunately not all CUC are responsive to RT Histological Radiation Response of the CUC according to Saryadi and Osborne (1975) determines 3 grades: good--moderate--poor HRR respectively, which conforms with the Cancer cells response grading according to National Cancer Center Hospital in Japan. In 1982, B. Hadiyanto and Sutoto reported a highly significant difference in the 5 y.s.r. of CUC patients who had better RHH (N = 52). In 1989, Sutoto, Suprijono and W. Adijono also reported highly significant differences among such groups of patients, of whom part received High-dosage of Mitomycin C (N = 46). Lately, Ristiyati and Sutoto have also found that the 5 y.s.r. among 187 patients treated with Radiotherapy alone and R.R. + Mitomycin showed significantly better survival in patients with better HRR. These studies showed that HRR is one of the most important points in CUC Radiotherapy. It has potential use in improving the result of RT, such as: Switching further treatment to surgery; Administering more aggressive adjuvant chemotherapy, among the worst responders. PMID- 1618223 TI - Expression and localization of epidermal growth factor receptors and ras oncogene products in gynecologic tumors. AB - We have investigated the expression of the products of two well-characterized oncogenes, erbB and Ha-ras, in the primary cultures of human gynecologic tumor cells by indirect immunofluorescent analysis. Epidermal growth factor receptor (c erbB gene product) and p21 (ras gene product) were highly expressed in 21 out of 26 cases (81%) and 14 out of 18 cases (78%), respectively. Furthermore, they were frequently co-localized in the same region of the cells. These results suggest that these two oncogene products may play a part in gynecologic tumorigenesis and that they can interact with each other. PMID- 1618224 TI - Cytoreductive surgery in the treatment of advanced ovarian carcinoma. Some controversial aspects. AB - Primary cytoreductive surgery in the treatment of advanced ovarian carcinoma is widely accepted and practiced. Its value has however never been established by controlled trials and the concept is therefore not unchallenged. Data with regard to the benefit of interval and secondary debulking are limited and often conflicting. Prospective randomized studies specifically designed to elucidate the controversies relevant to cytoreductive surgery are warranted. PMID- 1618225 TI - Combined radio-surgical treatment in early invasive cervix carcinoma according to prognostic factors. Experience of the Gustave-Roussy Institute. AB - In the Gustave-Roussy Institute the standard protocol of limited stages (IB, proximal II) of cervix carcinoma, combines endocavitary brachytherapy (low dose rate) and surgery (BSOH + lymphadenectomy) are eventually followed by external beam irradiation. According to age of patients and to prognostic factors adaptations of this combined treatment are discussed: young patient (40 years) with small tumor, large volume of primary tumor (4 cm), lymphatic node involvement. Analysis of the results in 2 series of patients entirely treated at the Gustave-Roussy Institute: survival, local control, metastases, complications. PMID- 1618226 TI - Serous tumors of the ovary: ultrastructural observations. AB - One borderline primary serous ovarian tumor and six carcinomas were studied by means of electron microscopy. Borderline malignant tumor evidenced concomitant presence of both benign and malign serous epithelium. Ultrastructural observations revealed differentiation characteristics which involved complex architecture of cell arrangement and polarity in the distribution of the organelle and intercellular junctions. The cilia believed to be more frequent in benign tumors were also reported in poorly differentiated carcinomas and so may not be considered as reliable prognostic markers. PMID- 1618227 TI - Improvement of combined method of cervix cancer therapy and evaluation of the results of its clinical use. AB - The results of combined therapy in 544 cervix cancer patients involving in the first step surgery (213 patients) or radiation combinations (331 patients) have been analysed. A method involving in the first step preoperative radiation ensuring a decrease in frequency of local-regional tumor recurrences was found to be more effective. The use of preoperative radiation by large-dose fractionation regimen proved to be reasonable, allowing us to avoid regrowth of tumor in the area of surgical and radiation attack without an increase in the number and severity of postoperative sequalae. PMID- 1618228 TI - Of mice and men... PMID- 1618229 TI - Alterations in an indium-111 Fab' under conditions of utilization. AB - This study was conducted to investigate alterations that occur in an indium/111 Fab' of a monoclonal antibody following its in vivo administration. Patients were infused with 111In-Fab' of the monoclonal antibody ZCE-025. Serum and urine specimens were collected from these patients. Starting materials, serum, urine and controls samples were studied by electrophoresis. Animal distribution studies were performed in normal Balb/c mice and, in some cases, nude mice bearing a carcinoembryonic antigen (CEA)/producing human colon tumour since the antibody targets CEA. The studies indicated that the molecule circulated almost totally intact for at least 4 h and to a considerable extent for 24 h, with some evidence for in vivo fragmentation by 24 h. Evidence was also obtained suggesting the formation of a high molecular weight species in some patients. Shortly after infusion, some of the 111In in the urine appeared as the intact Fab', but within hours the majority migrated electro-phoretically as low molecular weight species. We conclude that while the majority of the 111In-Fab' of this particular antibody remains intact and immunoreactive following its administration, the molecule is structurally changed to some degree shortly after its infusion into humans. Since each monoclonal antibody is unique, the degree and rapidity of degradation of its Fab' in vivo could vary markedly from the above and possibly adversely effect its utility as a radiopharmaceutical. PMID- 1618230 TI - Lymphoma imaging with a new technetium-99m labelled antibody, LL2. AB - The lesion detection capability of a new technetium-99m labelled B-cell lymphoma monoclonal antibody (MoAb) imaging agent, LL2, was evaluated in 8 patients with non-Hodgkin's lymphoma and 1 patient with chronic lymphocytic leukaemia. The MoAb kit consists of a 1-vial, 1-mg Fab' form of LL2 ready for instant labelling with technetium. The patients were injected with approximately 925 MBq (25 mCi) of 99mTc-LL2 Fab' (1 mg), and planar and single photon emission tomography (SPET) studies were performed at 3-4 h post injection and at 24 h. There was no evidence of thyroid or stomach activity up to 24 h. Uniform splenic uptake was seen in all patients. Two non-lymphoma patients were also administered with the same agent and demonstrated a similar splenic distribution; therefore, splenic targeting was not scored as tumour-specific. A total of 29 from 48 tumour sites were detected by scintigraphy, including tumours of various grades and histological types. Excluding 1 patient who had a large tumour burden of over 500 g, 29 of 33 lesions were detected. One patient was free of disease at the time of the study and had a negative scan. Another patient showed excellent targeting of gallium-negative sites in the liver and bone. The bone involvement was not known prior to the antibody study and was subsequently confirmed by a bone scan. Additional sites of MoAb localization could not be followed in this group, since most patients went on to radioimmunotherapy immediately following the 99mTc-LL2 study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618231 TI - The binding parameters of radiolabelled monoclonal F (ab')2 and Fab' fragments relative to immunoglobulin G in reactions with surface-bound antigens. AB - The binding parameters of iodine-125-labelled intact monoclonal immunoglobulin G (IgG), F(ab')2 and Fab' fragments were compared. The study was carried out with the two monoclonal antibodies (MoAbs) K13 and K16 specific for human Ig light chains kappa and lambda, respectively. When testing the 125I-MoAbs against monodisperse polymer particles coated with the specific antigens, the Ka for the F(ab')2 fragments were similar to that for IgG, while the Ka for the Fab' fragments were reduced to 10%-20% of that for IgG. The number N of effective target sites revealed with Fab' was higher than with F(ab')2 and IgG, presumably because less surface area is occupied by the small Fab' molecules. The immunoreactive fraction F ranged according to IgG greater than F(ab')2 greater than Fab'. The explanation of the moderate difference between the Ka of the monoclonal Fab' and the divalent IgG and F(ab')2 was that the divalent molecules were not divalently attached to the particles. When testing the same antibody preparations against human lymphoma cells producing Ig with light chains kappa or lambda, the binding results were less reliable than when particles were utilised, presumably due to antigen shedding. Different MoAbs vary in their loss of immunoreactivity due to enzymatic degradation and the radiolabelling procedure. The preparation of the radiolabelled fragments should therefore be optimized for each MoAb, and evaluation is necessary before injection. Artificial targets with a low leakage of antigen, like the monodisperse polymer particles here applied, are recommended for the in vitro evaluation of the immunoreactivity of labelled MoAb preparations. PMID- 1618232 TI - Tumour localization and pharmacokinetics of iodine-125 human monoclonal IgM antibody (COU-1) and its monomeric and half-monomeric fragments analysed in nude mice grafted with human tumour. AB - Human monoclonal IgM antibodies reactive with cancer-associated antigens may not have the optimal imaging capability due to their large size. Fragmentation of human IgM is less than straight-forward due to the loss of immunoreactivity. From the human monoclonal IgM antibody COU-1 we have prepared monomeric and half monomeric fragments, which retain the ability to bind to colon cancer cells in vitro. The pharmacokinetics and tumour localization were evaluated in nude mice bearing human colon adenocarcinoma and human melanoma grafts. Faster clearance from the circulation was seen for the smaller half-monomeric fragment with a half life (rapid phase/slow phase) of 2 h/16 h compared with the intact antibody, 4 h/25 h, and the monomeric fragment, 3 h/27 h. Intact COU-1 as well as the fragments accumulated in the colon tumour graft. Higher amounts of radioactivity were found in the colon tumour as compared to normal organs for intact COU-1 at days 4 and 6, for the monomeric fragment at day 4, and for the half-monomeric fragment at day 2 after injection. This investigation demonstrates the favourable biodistribution of the half monomeric COU-1 fragment. The fast clearance of this fragment resulted in a tumour-to-muscle ratio as high as 22 on day 2 after injection. Also, only this fragment gave a positive tumour-to-blood ratio. Normal IgM and its fragments were used as controls. Radioimmunoscintigraphy demonstrated the colon tumour discriminatory properties of each of the three iodine-labelled antibody preparations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618233 TI - Development of a high performance zinc-62/copper-62 radionuclide generator for positron emission tomography. AB - Clinical utilisation of positron emission tomography could be enhanced by the availability of short-lived radionuclides derived from generator systems. The zinc-62/copper-62 combination is one such system which could be used as a source for a number of copper-62 radiopharmaceuticals. We have developed and optimised a high activity (5.6 GBq, 150 mCi) zinc-62/copper-62 generator to provide 62Cu in a form that is suitable for direct labelling of pyruvaldehyde-bis-(N4 methylthiosemicarbazone)-copper(II), Cu(PTSM). The distribution coefficients of Zn(II) and Cu(II) between anion-exchange resin and various hydrochloric acid/organic solvent mixtures were measured. Based on these measurements a generator eluent of 0.3 M HCl/40% ethanol provided 62Cu in greater than 90% yield in a 3-ml volume. A very low 62Zn breakthrough of less than 3 x 10(-7)% was achieved. Copper-PTSM was successfully labelled with the no-carrier-added 62Cu eluent directly from the generator with 94% radiochemical yield. PMID- 1618234 TI - A method of computerised isotope dynamic proctography. AB - Patients with long-standing constipation were examined by radioisotope proctography. A radiolabelled synthetic potato mash was inserted intrarectally and the dynamic changes during simulated defaecation recorded using a gamma camera. Computer images from the stored data illustrate changes in the anorectal angle and pelvic floor. The median (and 95% confidence intervals) of the anorectal angles were: at rest 105 degrees (101 degrees, 116 degrees), on voluntary contraction of the pelvic floor by 'squeezing' 91 degrees (81 degrees, 98 degrees), on straining 120 degrees (107 degrees, 137 degrees) and during evacuation 126 degrees (116 degrees, 153 degrees). The pelvic floor movements were: pelvic floor ascent on voluntary contraction 28 mm (9, 34 mm), pelvic floor descent on straining -8 mm (-14, -4 mm) and descent during evacuation -27 mm ( 34, -11 mm). Useful additions to previous methods are measurement of the completeness of rectal evacuation 58% (42, 77%), the defaecation time 64 s (50, 138 s) and the defaecation rate 0.9%/s (0.4, 1.4%/s). PMID- 1618235 TI - Evaluation of monoclonal idiotypic-specific antibodies as clearing antibodies for enhancement of target localisation by tumour-specific monoclonal antibodies: diversity of effects in nude mice with human tumour xenografts. AB - Three tumour-specific monoclonal antibodies (MoAbs) showed localisation in human tumour xenografts in nude mice, although the tumour discrimination was limited by the survival of a greater proportion of the MoAb in the blood and body as a whole. An attempt was made to increase tumour discrimination by the subsequent administration of syngeneic idiotypic-specific MoAbs (anti-id) directed against the first antibodies, in the expectation of clearing excess of the first MoAb from the circulation. With one MoAb (NCRC-2), its anti-id (NCRC-60) did effectively clear it from the blood, and, at least within a few hours, the tumour to-blood ratios were increased. After longer periods, however, the tumour levels of NCRC-2 were also reduced, and the tumour discrimination was no longer increased. With another MoAb (NCRC-23) the tumour levels were reduced to a greater extent than were the blood levels in mice treated with its anti-id (NCRC 59), so that rather than being increased the tumour discrimination was actually reduced to about a third of that in control mice. With a third MoAb (NCRC-48), there was no effect on the tumour or blood levels within a few hours of injection of its anti-id (NCRC-62), and so there was no short-term effect on tumour discrimination. Subsequently, however, the tumour levels were slightly reduced, while the blood levels increased in mice treated with anti-id compared with control mice, so that the tumour-to-blood ratios decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618236 TI - Comparison of stress-only vs. stress/rest with technetium-99m methoxyisobutylisonitrile myocardial perfusion imaging. AB - Unlike conventional thallium-201 myocardial imaging, technetium-99m methoxyisobutylisonitrile (MIBI) requires separate stress and rest injections. We prospectively studied 148 consecutive patients referred for myocardial perfusion studies to determine the diagnostic value of rest images once normal exercise or dipyridamole tomographic images had been obtained. In patients referred with no history of previous myocardial infarction in whom the diagnosis of coronary artery disease was suspected, 45 of 109 (41%) patients had normal stress tomographic images. Obtaining rest images did not alter the final interpretation in any of these cases. From this we infer that in patients with normal images after exercise or dipyridamole administration and no past history of myocardial infarction, 99mTc-MIBI rest images are not required. This provides several advantages including increased speed of diagnosis, decreased patient radiation exposure, improved cost efficiency and decreased demand on tomographic camera time. PMID- 1618237 TI - Combined nuclear and digital subtraction contrast arthrography in painful knee prosthesis. AB - The evaluation of a painful knee prosthesis remains a difficult problem for both orthopaedic surgeons and radiologists. We have compared digital subtraction arthrography with nuclear arthrography in 7 patients with a painful knee prosthesis. Three patients showed a loose tibial component, demonstrated by both digital subtraction and nuclear arthrography. All 3 underwent revision of their prosthesis. One patient had an equivocal digital subtraction arthrogram and negative nuclear arthrogram, while both studies were negative in the 3 remaining patients. Nuclear arthrography is a simple procedure and can provide useful additional information when combined with digital subtraction arthrography. PMID- 1618238 TI - Scintigraphic evaluation of the pharmacokinetics of a soluble polymeric drug carrier. AB - There is a growing interest in the use of macro-molecular carriers for therapeutic agents. If these carriers can be labelled with an appropriate gamma emitter, their biodistribution could be followed by scintigraphy. We have imaged the biodistribution of a synthetic branched polypeptide, based on a poly-L-lysine backbone (average molecular mass 45 kDa). The polymer was conjugated to diethylene triamine penta-acetic acid and labelled by chelation with indium-111. Mice were injected i.v. with labelled material and imaged with a gamma-camera with a pin-hole collimator. Images showed the majority of tracer remaining in the blood pool, but about 35% appeared in the urinary bladder within 1.5 h. When the 111In-polymer was fractionated by gel filtration chromatography on S-300, the imaging showed that the early eluting material was retained, the intermediate showed some renal clearance, and the late was rapidly excreted. These findings show the value of gamma-scintigraphy for biodistribution studies with such polymeric drug carriers and its potential for clinical pharmacokinetic studies. PMID- 1618239 TI - Imaging of metabolism and autonomic innervation of the heart by positron emission tomography. AB - Positron emission tomography (PET) allows, in combination with multiple radiopharmaceuticals, unique physiological and biochemical tissue characterization. Tracers of blood flow, metabolism and neuronal function have been employed with this technique for research application. More recently, PET has emerged in cardiology as a useful tool for the detection of coronary artery disease and the evaluation of tissue viability. Metabolic tracers such as fluorine-18 deoxyglucose (FDG) permit the specific delineation of ischaemically compromised myocardium. Clinical studies have indicated that the metabolic imaging is helpful in selecting patients for coronary artery bypass surgery or coronary angioplasty. More recent research work has concentrated on the use of carbon-11 acetate as a marker of myocardial oxygen consumption. Together with measurements of left ventricular performance, estimates of cardiac efficiency can be derived from dynamic 11C-acetate studies. The non-invasive evaluation of the autonomic nervous system of the heart was limited in the past. With the introduction of radiopharmaceuticals which specifically bind to neuronal structures, the regional integrity of the autonomic nervous system of the heart can be evaluated with PET. Numerous tracers for pre- and postsynaptic binding sites have been synthesized. 11C-hydroxyephedrine represents a new catecholamine analogue which is stored in cardiac presynaptic sympathetic nerve terminals. Initial clinical studies with it suggest a promising role for PET in the study of the sympathetic nervous system in various cardiac diseases such as cardiomyopathy, ischaemic heart disease and diabetes mellitus. The specificity of the radio-pharmaceuticals and the quantitative measurements of tissue tracer distribution provided by PET make this technology a very attractive research tool in the cardiovascular sciences with great promise in the area of cardiac metabolism and neurocardiology. PMID- 1618240 TI - The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis. AB - We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Trisalicylate and ibuprofen both significantly reduced methotrexate renal clearance, but only the trisalicylate significantly displaced methotrexate from protein, increasing the fraction unbound by 28%. These data show that NSAIDs can affect the disposition of methotrexate, possibly increasing the potential for toxicity and necessitating dosage adjustments. However, large inter-subject variability precludes specific dosage recommendations. PMID- 1618241 TI - Pravastatin and lovastatin similarly reduce serum cholesterol and its precursor levels in familial hypercholesterolaemia. AB - The hypocholesterolaemic effect of pravastatin 40 mg and lovastatin 40 mg daily has been compared in patients with familial hypercholesterolaemia (FH). Administration of the two drugs was separated by a three-month washout period. The reduction in total serum cholesterol after 1,2 and 4 weeks of treatment was similar after pravastatin (-23%, -32% and -32%) and lovastatin (-23%, -30% and 31%). The serum concentrations of LDL cholesterol were similarly reduced, whilst triglycerides, other lipoproteins, cholestanol and squalene were not altered. The reductions in the serum levels of the cholesterol precursor sterols, delta 8 cholesterol, desmosterol and lathosterol were not significantly different after either drug. The lack of difference suggests that cholesterol synthesis was equally inhibited by the two agents. In addition, the serum content of the plant sterols campesterol and sitosterol tended to be equally increased. The comparability of the increases suggests that the absorption and biliary elimination of the two sterols were equally affected by the two statins. Thus, no difference was found between the effects of pravastatin and lovastatin on the serum levels and metabolic precursors of cholesterol in FH during four weeks of treatment. PMID- 1618242 TI - Ambulatory blood pressure monitoring for the assessment of nicardipine as a third drug in severe essential hypertension. AB - The antihypertensive efficacy of sustained-release nicardipine compared to placebo as third-line therapy has been assessed by ambulatory blood pressure monitoring in severely hypertensive patients with clinically unsatisfactory blood pressure control on 50 mg hydrochlorothiazide o.d. and 75 mg captopril b.d. Forty two patients, 31 m and 11 f, with supine diastolic blood pressure 95-115 mm Hg after a 4 week run-in period on open hydrochlorothiazide and captopril, were randomly allocated to sustained-release nicardipine 45-60 mg/d or placebo. At a visit to the clinic blood pressure and heart rate were measured 12 h after the evening dose by a trained observer unaware of the treatment. Twenty-four hour ambulatory monitoring was performed at the end of baseline and after 8 weeks of blinded medication. There was no significant change in BD at the visit or on ambulatory monitoring in the placebo treated patients. In contrast, nicardipine produced a significant reduction in both blood pressures without affecting heart rate. Nicardipine also decreased the mean 24-h blood pressure by 14/10 mm Hg in patients whose clinical hypertension had been confirmed by ambulatory blood pressure monitoring but by only 3/2 mm Hg in ambulant patients who were normotensive on two-drug therapy. One patient experienced an episode of severe symptomatic hypotension while on nicardipine. Otherwise, the numbers and percentages of patients from each group reporting adverse experiences were similar. It is concluded that nicardipine appears to be an effective antihypertensive agent when used as third line therapy with diuretics and angiotensin converting enzyme inhibitors in patients with severe hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618243 TI - Intravenous amine pressor tests in healthy volunteers. Within- and between subject variances and sex differences. AB - The pressor effect of intravenous tyramine (TYR) and noradrenaline (NA) has been evaluated, respectively, in 157 tests in 19 healthy unmedicated subjects, and in 202 tests in 24 similar subjects, all of whom took part in greater than or equal to 3 test sessions. The pressor dose (PD) that raised systolic blood pressure by 30 mm Hg (PD30) ranged from 2 to 8 mg for TYR, and from 3.5 to 17 micrograms.min 1 for NA. Coefficients of variation ranged from 3 to 47% and from 6 to 38% for TYR and NA, respectively, in the intra-subject comparison. The average inter subject variation in the TYR PD30 was 22% for 8 females and 30% for 11 males; the corresponding variation in the NA PD30 was 27% (8 females) and 26% (16 males). While the average PD30 for NA was similar for males (10.8 micrograms/min) and females (10.9 micrograms/min), a sex-related difference was found for the PD30 of i.v. TYR: 4.4 mg for 11 males and 3.8 mg for 8 females. Additional results from volunteers who took part in fewer than 3 pressor test sessions supported this observation; PD30 of TYR 4.6 mg in 34 males vs 3.5 mg in 21 females. The large intra- and inter-subject variations in the i.v. TYR and NA pressor test results, and the sex difference in the systolic blood pressure response to i.v. TYR, should be considered in assessing the number and gender of subjects required in studies intended to show "significant" differences in the blood pressure response in amine pressor tests. PMID- 1618244 TI - Acute changes in forearm haemodynamics produced by cigarette smoking in healthy normotensive non-smokers are not influenced by propranolol or pindolol. AB - The aim of the present study was to examine the effect of cigarette smoking in healthy non-smokers on blood pressure and forearm haemodynamics after acute oral administration of non-selective beta-adrenoceptor blockers with and without intrinsic sympathomimetic activity, viz. pindolol 15 mg and propranolol 80 mg. A preliminary study was done to compare cigarette smoking and sham smoking to evaluate the time-course of the haemodynamic effects of cigarette smoking. The second experiment was then carried out in the same six volunteers, according to a double-blind randomized placebo-controlled crossover design, to evaluate the possible effect of pre-treatment with beta-adrenoceptor blockers on blood pressure, heart rate and forearm haemodynamics (forearm blood flow, brachial artery diameter and brachio-radial pulse-wave velocity) measured at baseline, during smoking and every five minutes up to 1 h afterwards. No major difference from placebo in blood pressure or forearm haemodynamics was found and pre treatment with beta-blockers did not prevent the acute vascular effects of cigarette smoking. PMID- 1618245 TI - Differences in antidiabetic drug utilisation between three different health systems in the same national region. AB - The consumption of antidiabetic drugs in a Spanish region (Extremadura) in the period 1986-1987 has been investigated by the "defined daily dose" (DDD) method. The study was done in three health care systems in the region: civil servants ("Mutualidad de Funcionarios Civiles del Estado: MUFACE") armed forces group ("Instituto Social de las Fuerzas Armadas: ISFAS") and the national system ("Instituto Nacional de la Salud: INSALUD"). The total consumption of antidiabetic drugs varied three-fold, ranging from 5,73 DDD per 1000 inhabitants per day (3,71 DDD per 1000 inhabitants per day for oral antidiabetic drugs and 2,02 DDD per 1000 inhabitants per day for insulin) in the civil servant group to 15,82 DDD per 1000 inhabitants per day (12 DDD per 1000 inhabitants per day for oral antidiabetic drugs and 3,82 DDD per 1000 inhabitants per day for insulins) in the armed forces. The differences were more pronounced for oral antidiabetics than for insulins. The utilization of insulin among the civil servants was about half of that by the two other groups. Of oral antidiabetics, sulphonylureas were the most frequently used by the three groups, and within them glibenclamide accounted for more than half of the DDDs, while biguanides were scarcely used in any group. The differences are difficult to assess, since they could be due to several factors, such as age-differences in the population studied, different prescribing habits, and differences in sociocultural level. The results justify further comparative studies of drug utilization in different health systems within the same region. PMID- 1618246 TI - The effects of two different local anaesthetic solutions administered for oral surgery on plasma potassium levels in patients taking kaliuretic diuretics. AB - The effects of two different dental local anaesthetic solutions, administered for oral surgery, on the plasma potassium levels of patients taking non-potassium sparing diuretics has been investigated. There was a significant reduction in plasma potassium concentration in eight subjects who received 4.4 ml of 2% lignocaine with 1:80,000 adrenaline; the mean reduction from baseline being 0.30 mmol.l-1 10 min following intraoral extravascular injection of the local anaesthetic. There was no significant difference from the pre-treatment plasma potassium concentration 10 min following similar injections of 3% prilocaine with 0.03 IU.ml-1 felypressin in 8 patients; the mean change in these subjects being 0.05 mmol.l-1. It is suggested that the use of adrenaline-free local anaesthetics would seem to be appropriate in patients receiving kaliuretic diuretics. PMID- 1618247 TI - 0.25% prednicarbate cream and the corresponding vehicle induce less skin atrophy than 0.1% betamethasone-17-valerate cream and 0.05% clobetasol-17-propionate cream. AB - The atrophogenic potential of medium-potent topical glucocorticoids is still controversial. In a double-blind controlled trial 24 healthy volunteers either applied 0.25% prednicarbate cream or the corresponding vehicle to one and 0.1% betamethasone-17-valerate cream or 0.05% clobetasol-17-propionate cream to the other forearm twice daily. Skin thickness was regularly assessed during the six week period of application and for further three weeks thereafter, using both the B- and A-mode of a 20 MHz ultrasound scanner. Both betamethasone-17-valerate and clobetasol-17-propionate cream significantly reduced skin thickness as compared to cream base while prednicarbate cream did not. Given that 0.1% betamethasone-17 valerate- and 0.25% prednicarbate cream are reported to be about equipotent in the treatment of atopic eczema the latter preparation shows an increased ratio between its desired anti-inflammatory and its unwanted atrophogenic effect. PMID- 1618248 TI - Disposition of quinine in plasma, red blood cells and saliva after oral and intravenous administration to healthy adult Africans. AB - The pharmacokinetics of quinine has been studied in ten healthy adult Africans after intravenous infusion and oral ingestion of a 500 mg dose. Blood and saliva samples were collected over 48 h and quinine in plasma, red cells and saliva was determined by HPLC. Quinine was rapidly and almost completely absorbed after an oral dose, with absorption half-life of 0.53 h, a tmax of 1-3 h and a bioavailability of 88%. Analysis of the i.v. data gave an apparent volume of distribution of 3.6 l.kg-1 and a plasma clearance of 0.19 l.kg-1.h-1. The concentration-time curves for plasma, red cells and saliva had declining phases were approximately parallel, giving a similar half-life that in all three media. The half-lives after the i.v. infusion also did not different from those after oral administration. The dose was well tolerated by both methods of administration. PMID- 1618249 TI - Binding of a metabolite of triflusal (2-hydroxy-4-trifluoromethylbenzoic acid) to serum proteins in rat and man. AB - 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) is the main active metabolite of the platelet antiaggregant drug triflusal. Its binding to plasma proteins of rats and healthy volunteers in vitro and in vivo has been studied. Rats were given a single oral dose of 50 mg.kg-1 triflusal and the healthy volunteers received 300 mg as a single oral dose or a multiple dose regimen of 600 mg every 24 h and 300 mg every 8 h, both for 13 days. Protein-free HTB was obtained by ultrafiltration. Unbound and total HTB concentrations were determined by HPLC. HTB was primarily bound to albumin in plasma. The Scatchard plots suggested two types of binding sites for HTB on the albumin molecule. In rats, the binding constants (K = intrinsic affinity constant, n = number of binding sites) were K1 = 1.4 x 10(5) l.mol-1, n1 = 1.23, and K2 = 4.1 x 10(3) l.mol-1 and n2 = 3.77. The mean plasma concentration in rats after oral administration was 185 (37) micrograms.ml-1 (protein-free HTB:2.44 (0.77)%). The binding constants in human plasma were K1 = 4.7 x 10(5) l.mol-1, n1 = 1.93, K2 = 4.3 l.mol-1 and n2 = 4.28. The plasma HTB concentration in man (n = 8) was 35 micrograms.ml-1 (Cmax) after a single oral dose of triflusal 300 mg, 172.96 micrograms.ml-1 (Cmax.ss) during the multiple dosage regimen of 300 mg every 8 h, and 131 micrograms.ml-1 (Cmax.ss) during the multiple oral dose regimen of 600 mg every 24 h. Unbound HTB ranged from 0.27 to 0.43%, depending on dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618250 TI - Temporary reversal of serum to cerebrospinal fluid glycerol concentration gradient after intravenous infusion of glycerol. AB - Glycerol 50 g infused i.v. over 2 to 6 h is widely used to treat cerebral oedema in patients with acute stroke. Its transit through the blood-cerebrospinal fluid barrier in subjects with uninflamed meninges has now been examined. In 7 patients with an external ventriculostomy for occlusive hydrocephalus, each of whom was given 500 ml of a 10% solution IV over 4 h, serum and CSF were repeatedly sampled during and after the infusion and glycerol was measured enzymatically. The highest serum glycerol level of 191-923 mg/l was observed at the end of the infusion. The maximum CSF glycerol of 18.7-110.8 mg/l was attained 0-1 h after the end of the infusion. Elimination both from serum and CSF approximated a single-exponential decay; the elimination half-life from serum was 0.29-0.56 h compared to 1.03-3.68 h from CSF. In six of the seven cases there was a temporary reversal of the serum/CSF concentration gradient during glycerol elimination. The ratios of the AUCs of CSF and serum, which describe the overall penetration of glycerol into CSF, ranged from 0.09-0.31. In conclusion, the serum level of glycerol produced by giving 50 g IV glycerol over 4 h may not be sufficiently high reliably dehydrate to brain tissue in many patients, and the slow elimination of glycerol from the CSF may be related to the so-called rebound phenomenon. PMID- 1618251 TI - Formation and excretion of dipyrone metabolites in man. AB - The formation and urinary excretion of the dipyrone metabolites, methylaminoantipyrine (MAA), aminoantipyrine (AA), formylaminoantipyrine (FAA) and acetylaminoantipyrine (AAA) were determined following administration of a single oral 1.0 g dose of dipyrone to 12 healthy volunteers. The AAA/AA plasma ratio showed that 3 subjects were slow and 9 were rapid acetylators. Pharmacokinetic parameters were determined separately for each group. A good correlation was found between the plasma and urine AAA/AA ratios. The renal clearance of the four metabolites was similar for both phenotypes. A significant difference in the rate of formation of dipyrone metabolites was found for AA, 0.25 (slow) vs 0.1 ml.min-1.kg-1 (rapid), and for AAA 0.75 (slow) vs 7.53 ml.min 1.kg-1 (rapid). There were comparable differences between slow and rapid acetylators in the AUC and the urinary excretion extrapolated to infinity for AA and AAA. The present results show that the kinetics of dipyrone metabolites in plasma and urine can provide a useful measure of the activity of the enzymes involved in their production. PMID- 1618252 TI - Prediction of creatinine clearance by several methods in patients with severe infections. AB - Since almost all urinary creatinine is derived from the muscle mass, the amount of creatinine in the urine will be proportional to muscle mass, and it will show an almost constant decrease with age. A simple equation for estimating creatinine clearance has been derived. For women the creatinine clearance (ml.min-1) was [150-(years)].body weight (kg)/serum creatinine (mumol.l-1). For men less than 70 years it was [170-age (years)].body weight (kg)/serum creatinine (mumol/l) and for men greater than or equal to 70 years it was [160-age (years)].body weight (kg)/serum creatinine (mumol/l). The prediction was quite simple when laboratory results were given in SI units. A simple nomogram was devised for easy estimation of the creatinine clearance in individual patients according to the age, sex and weight. Predicted values according to our equations were compared with those derived from other formulae in 54 patients with severe infections treated with aminoglycosides. No major differences were found, but the new method seemed more convenient. PMID- 1618253 TI - Effect of salbutamol on digoxin pharmacokinetics. AB - A single dose of the beta 2-adrenoceptor agonist salbutamol has previously been shown to decrease serum digoxin concentration in healthy volunteers. A possible explanation of the phenomenon is a beta 2-adrenoceptor-mediated increase in the specific binding of digoxin to skeletal muscle. The present study was undertaken to further elucidate the effect of salbutamol on the pharmacokinetics of digoxin in man. Nine volunteers were studied on two occasions during salbutamol or placebo treatment. On test days salbutamol, 4 micrograms.kg-1.h-1 or saline was infused for 10 h, preceded and followed by four and three days, respectively, of oral administration. A single i.v. injection of digoxin 15 micrograms.kg-1, was given 20 min after starting the infusion. At the end of the infusion a muscle biopsy was taken from the vastus lateralis. Blood samples for the analysis of serum digoxin and potassium were repeatedly taken over 72 h. Urine was collected over a period of 24 h for determination of the renal excretion of digoxin and potassium. The serum digoxin concentration, expressed as the AUC 0-6 h was 15% lower during salbutamol infusion than during saline infusion. Salbutamol caused significantly faster elimination of digoxin from the central volume of distribution to deeper compartments. Salbutamol had no effect on the renal clearance of digoxin. The skeletal muscle digoxin concentration tended to be higher (48%) during salbutamol compared to placebo treatment. The serum potassium concentration was significantly lower after salbutamol compared to placebo, as was the rate of renal excretion of potassium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618254 TI - Lack of effect of omeprazole, cimetidine, and ranitidine on the pharmacokinetics of ethanol in fasting male volunteers. AB - The effects of three gastric antisecretory drugs on the pharmacokinetics of ethanol have been studied in a randomized crossover experiment. Male medical students (n = 12) took ethanol 0.8 g/kg body weight at 08.00 h after an overnight fast. On seven successive days before drinking ethanol they were given omeprazole 20 mg, cimetidine 800 mg, ranitidine 300 mg, or no drug, with a period of at least 7 days between treatments. The peak blood ethanol concentration of 21.9 to 22.8 mmol.l-1 occurred at 64 to 70 min after the end of drinking. The rate of disappearance of ethanol from the blood ranged from 3.0 to 3.3 mmol.l-1.h-1 and the rate of removal from the whole body ranged from 8.0 to 8.5 g.h-1. The apparent volume of distribution of ethanol was almost the same for all four treatments: mean 0.68 l.kg-1, corresponding to a mean total body water of 44 l (59% body weight). Mean areas under the concentration-time profiles of ethanol ranged from 83 to 87 mmol.l-1.h for the four treatments. It is concluded that omeprazole, cimetidine and ranitidine do not alter the kinetics of a moderate dose of ethanol. PMID- 1618255 TI - Influence of verapamil on the coronary arteriovenous difference in long chain free fatty acids in hypertrophic cardiomyopathy. AB - The percentage composition of free fatty acids in the coronary circulation has been studied during the passage of blood through the heart in patients with hypertrophic cardiomyopathy. Under basal conditions the percentages of palmitic and stearic acid decreased significantly. Verapamil i.v. produced a tendency towards a preferential myocardial uptake of oleic acid. PMID- 1618256 TI - Plasma thiamine concentrations after intramuscular and oral multiple dosage regimens in healthy men. AB - A novel liquid chromatographic method for the determination of thiamine in plasma has been developed and has been used to study plasma thiamine concentrations after multiple dosage regimens for 11 days. The method involves purification, concentration and analytical separation of thiochrome on-line, using a switching column system. Ten healthy men were given 500 mg thiamine i.m. once a day (Group 1) and ten were given 250 mg p.o. every 12 h (Group 2). The times to reach steady state (7 and 5.6 days for Groups 1 and 2, respectively) were not different (P greater than 0.05). The mean elimination half-life was 1.8 days. The mean minimum steady-state concentration after the oral regimen (23 micrograms.l-1) was 78% of that after the intramuscular regime (29 micrograms.l-1). PMID- 1618257 TI - Absence of interaction between tenoxicam and warfarin. AB - The influence of tenoxicam on plasma warfarin concentrations and on its anticoagulant effect has been studied in healthy volunteers. Tenoxicam did not alter the plasma warfarin concentration versus time profile. Treatment with it for 14 days had no effect on the average dose of warfarin required to maintain the prothrombin time within a specified range. The coumarin dose index, an indicator of warfarin sensitivity, remained unchanged during tenoxicam administration. The results demonstrate the lack of a clinically relevant effect of tenoxicam on warfarin-induced anticoagulation. PMID- 1618258 TI - No effect of cisapride on paracetamol absorption after oral simultaneous administration. AB - We have measured the effect of oral cisapride on paracetamol absorption in 12 healthy volunteers in a double-blind placebo-controlled study. Volunteers received paracetamol plus placebo, paracetamol plus cisapride 10 mg and paracetamol plus cisapride 20 mg. Mean plasma paracetamol AUC at 60 min were 1070, 1051 and 1031 micrograms.min.ml-1 and maximum paracetamol concentrations were 31.5, 29.3 and 27.4 micrograms.ml-1 respectively (no significant differences). There was no difference also in time to maximum paracetamol concentration [median (range) 30 (15-120), 30 (15-90) and 30 (15-60) min, respectively]. . PMID- 1618259 TI - Drinking induced by subcutaneous injection of angiotensin II in the rat is blocked by the selective AT1 receptor antagonist DuP 753 but not by the selective AT2 receptor antagonist WL 19. AB - The role of AT1 and AT2 receptors in mediating the drinking response induced by angiotensin II in the rat was examined. Angiotensin II (0.1-1.0 mg/kg s.c.) caused a dose-dependent increase in drinking in water-replete rats. The angiotensin Il-induced drinking response was dose dependently blocked by the selective AT1 receptor antagonist DuP 753 (1-30 mg/kg s.c.). In contrast, the selective AT2 receptor antagonist WL 19 failed to block angiotensin II-induced drinking up to doses of 100 mg/kg s.c. and significantly enhanced the response at 3 and 100 mg/kg. These data suggest that drinking induced by angiotensin II is mediated by AT1 receptors and that AT2 receptor activation may inhibit the drinking response. PMID- 1618260 TI - Anti-IL-5 monoclonal antibody inhibits allergic late phase bronchial eosinophilia in guinea pigs: a therapeutic approach. AB - In this study the effect of purified rat anti-mouse IL-5 monoclonal antibody on aeroallergen-induced infiltration of eosinophils in the bronchoalveolar lavage fluid of guinea pigs was studied. The i.p. injection of anti-IL-5 antibody 4 h after aeroallergen challenge inhibited eosinophil infiltration in a dose dependent fashion. The resulting ED50 was 10 (3.4-32.8) micrograms/kg. The clinical therapeutic usefulness of anti-IL-5 or anti-IL-5-producing cells in asthma/allergy treatment remains to be an intriguing possibility. PMID- 1618261 TI - Carbon monoxide does not inhibit glyceryl trinitrate biotransformation by or relaxation of aorta. AB - Carbon monoxide (CO) was employed to assess the role of ferrous hemoproteins in the vasodilation and biotransformation of glyceryl trinitrate (GTN) in rabbit aortic strips. These tissues were contracted submaximally with phenylephrine, exposed to CO for 5 min, and then incubated with 0.5 microM [1,3(14) C]GTN in the presence of CO for 2 min or 30 s. The [14C]GTN-induced relaxation of the strips was recorded, and [14C]GTN biotransformation to [14C]glyceryl dinitrate metabolites by the tissues was determined by thin-layer chromatographic-liquid scintillation spectrometric analysis. CO treatment inhibited neither GTN-induced relaxation nor GTN biotransformation to glycerol dinitrate metabolites. These results indicate that ferrous hemoproteins are probably not involved in the biotransformation of GTN that is associated with relaxation of the rabbit aortic strips. PMID- 1618262 TI - The potent 5-HT3 receptor antagonist (R)-zacopride labels an additional high affinity site in the central nervous system. AB - The binding characteristics of [3H](R)- and [3H](S)-zacopride were investigated in membranes from the rat entorhinal cortex and NG 108-15 clonal cells. In contrast to [3H](S)-zacopride which bound solely to 5-HT3 receptors, [3H](R) zacopride recognized another class of binding sites, called the (R)-sites, in both membrane preparations. In addition to (R)-zacopride (Ki = 3-11 nM), only (R) iodo-zacopride, (R)-dechloro-zacopride, prazosin and mianserin exhibited high to moderate affinity for the (R)-sites, whose possible functions remain to be established. PMID- 1618263 TI - Differential effects of picrotoxin and RO 15-1788 on high and low ethanol concentrations on rat locus coeruleus in vitro. AB - In an in vitro electrophysiological single-cell recording model, ethanol had an inhibitory effect on locus coeruleus (LC) neurons at both low (0.1 mmol/l) and high (500 mmol/l) concentrations. In order to test if the benzodiazepine-GABA (gamma-aminobutyric acid) receptor complex could be implicated in this effect, we tested the interaction of these ethanol concentrations with picrotoxin (100 mmol/l) and RO 15-1788 (10 nmol/l). RO 15-1788 reversed the inhibitory effect induced by ethanol 500 mmol/l, but not by ethanol 0.1 mmol/l; picrotoxin reversed the effects of both concentrations. This indicates that the mechanisms of action of ethanol on LC neurons are not the same for high and low concentrations. Furthermore, the effect of concentrations related to a behavioral effect (greater than 10 mmol/l) was reversed by a low-calcium medium that abolishes transmitter release. Therefore, the inhibition induced by ethanol 500 mmol/l seems to be due to the release of an endogenous benzodiazepine-like compound. PMID- 1618264 TI - Corticotropin-releasing hormone excites myenteric neurons in the guinea-pig small intestine. AB - The electrophysiological actions of corticotropin-releasing hormone (CRH) on myenteric neurons from the guinea-pig ileum were studied by intracellular microelectrode recording. CRH, when applied by micropressure ejection or in the medium (0.2-20 nM) evoked prolonged depolarization in 21 of 42 S/type 1 neurons and in 28 of 40 AH/type 2 neurons. These responses were associated with increased input resistance and augmented excitability. The post-spike hyperpolarization in AH/type 2 cells was suppressed during the CRH-evoked responses. The reversal potential of the response to CRH was about -90 mV, consistent with the closure of potassium channels by the peptide. The CRH-induced depolarization was prevented by incubation in 10 microM 5'-N-ethylcarboxamidoadenosine (NECA, an adenosine analog) suggesting that the response was mediated by stimulation of adenylate cyclase and elevation of cAMP. CRH reduced the amplitude of fast nicotinic excitatory postsynaptic potentials. This appeared to be a postsynaptic action because the peptide also reduced the responses to exogenously applied acetylcholine. These results suggest that CRH can directly influence intestinal function by acting on myenteric neurons. PMID- 1618265 TI - Differential inhibition by the PAF receptor antagonist, WEB 2170, of allergic inflammation in single sensitized and boosted mice. AB - Interference of the PAF antagonist, WEB 2170, with the paw edema induced by antigen in boosted or unboosted sensitized mice was investigated. Edema was triggered by the intraplantar injection of ovalbumin to animals actively sensitized 21 days before and that received (boosted), or did not receive (unboosted), a second immunization after 14 days. There was no difference in the intensity of the response to antigen or to PAF (platelet-activating factor) in boosted or in unboosted animals. Intraperitoneal treatment with WEB 2170 1 h before challenge reduced dose dependently the edema in boosted mice but did not modify the reaction in unboosted mice. It is noteworthy that WEB 2170 was more effective against PAF-induced paw edema in unboosted than in boosted mice, the maximum inhibition of 84% being reached at 16 mg/kg. In addition, topical and selective desensitization to PAF inhibited the edema caused by antigen only in boosted animals. Our findings indicate that the booster injection during the immunization process shifts the anaphylactic mouse paw edema from a PAF independent to a PAF-dependent reaction. PMID- 1618266 TI - Effects of yohimbine on morphine analgesia and physical dependence in the rat. AB - The effects of yohimbine on morphine analgesia and on the development of opiate physical dependence were studied to find out more about the involvement of alpha 2-adrenergic mechanisms in opioid actions. Male Sprague-Dawley rats (250-300 g) were used. The acute effect of morphine (5 mg/kg i.p.) in the tail-flick test was reduced significantly by pretreatment with a single dose of yohimbine (2 mg/kg i.p.). Alone yohimbine, produced a slight hyperalgesia. Animals treated with a sustained-release preparation of morphine (300 mg/kg s.c.) showed the same sensitivity to opiate analgesia 72 h later whether they were treated concomitantly with yohimbine or not, but they exhibited fewer withdrawal symptoms upon naloxone injection after yohimbine (2 or 4 mg/kg i.p. 24, 28, 48 and 52 h after the start of systemic morphine treatment). The results obtained confirm previous data on the effects of yohimbine on morphine analgesia and reveal the importance of alpha 2-adrenergic activation in the development of opioid physical dependence. PMID- 1618267 TI - Effect of the beta-adrenoceptor antagonist, propranolol, on feeding induced by noradrenaline and muscimol in rats kept at high and temperate-ambient temperatures. AB - Both the gamma-aminobutyric acid (GABA) receptor agonist, muscimol, and noradrenaline stimulated the feeding behavior of rats in the two environments. When noradrenaline or muscimol was administered, however, the food intake at 26 degrees C was greater than that at 33 degrees C. In addition, the stimulatory effect of noradrenaline on food intake was significantly depressed by propranolol pretreatment at both temperatures. The stimulatory effect of muscimol on food intake was significantly depressed by the propranolol pretreatment at 33 degrees C but not at 26 degrees C. Some eating-stimulatory subsystems associated with feeding behavior induced by noradrenaline or muscimol might have been depressed in the hot environment, thus the food intake increased by these drugs in rats acclimated to the hot environment was less than that in rats acclimated to the temperate environment. PMID- 1618268 TI - Elevated basal firing rates and enhanced responses to 8-Br-cAMP in locus coeruleus neurons in brain slices from opiate-dependent rats. AB - Extracellular, single unit activity was recorded in noradrenergic neurons of the nucleus locus coeruleus (LC) in brain slices prepared from rats treated chronically with morphine. In contrast to previous reports, basal firing rates of LC neurons were 2-fold higher in slices from opiate-dependent animals compared to controls and they remained elevated for at least 7 h. In neurons from dependent animals the maximal excitation in response to 8-bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP), but not the EC50, was found to be substantially greater than in controls. This result parallels biochemical evidence of an up regulation of the cAMP pathway in the LC of opiate-dependent animals. There was no difference in the response to glutamate between cells from dependent and control animals. We conclude that an increase in basal firing rate, possibly mediated by an up-regulation of the intrinsic cAMP pathway, contributes to the hyperactivity of the LC during opiate withdrawal in vivo. PMID- 1618269 TI - Comparison of peripheral and central nervous system sympatholytic actions of prazosin using the cat nictitating membrane. AB - Prazosin is a highly selective alpha 1-adrenoceptor antagonist that decreases blood pressure by actions on both the peripheral and central (CNS) divisions of the nervous system. The present investigation was undertaken in an attempt to characterize the relative contribution of these two sympatholytic sites of action. Submaximal contractions of the nictitating membranes were evoked by electrical stimulation of the preganglionic cervical sympathetic nerve trunk and by stimulation of the posterior hypothalamus in anesthetized cats. In initial control experiments, phenoxybenzamine (0.1-3.0 mg/kg i.v.) produced an equivalent depression of evoked nictitating membrane responses from both peripheral and CNS sites of activation which suggests only a peripheral blocking action as well as functional equivalence of the intensity of CNS and peripheral nerve stimulation. In contrast, prazosin (3-300 micrograms/kg i.v.) caused a differential dose related depression of the evoked responses with ED50s of 81.5 micrograms/kg (peripheral stimulation) and 12.5 micrograms/kg (CNS stimulation) respectively; P less than 0.05. Pretreatment with rauwolscine (500 micrograms/kg i.v.) totally prevented the differential CNS sympatho-inhibition produced by prazosin. These results indicate that, although both CNS and peripheral sites of drug action are manifest, the ED50 for prazosin-induced CNS sympatho-inhibition is approximately 6-fold less than that required for direct alpha 1-adrenoceptor blockade at the end organ. In addition, prazosin produces CNS sympatho-inhibition indirectly by means of an alpha 2-adrenoceptor mechanism. PMID- 1618270 TI - Inhibitory and stimulatory actions of danazol in rat ovarian and uterine tissues. AB - We examined whether danazol has a direct action on ovarian steroid secretion and/or uterine prostaglandin (PG) F2 alpha catabolic activity in immature rats in which the first ovulation was induced and in adult ovariectomized rats. The preovulatory surge of estradiol and progesterone was markedly suppressed together with that of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by danazol administration under conditions that blocked the first ovulation. Uterine weight and PGF2 alpha catabolic activity enhanced by endogenous estrogen were greatly decreased by danazol treatment at a dose that did not block the first ovulation in immature rats. When danazol (30 mg) was given s.c. once daily for 2 days to ovariectomized rats, the uterine weight and PGF2 alpha catabolic activity per uterus were clearly increased, and the compensatory increase in FSH levels as a result of castration was not influenced, although the compensatory increase in LH levels was inhibited. These results demonstrate that danazol has a direct action on the ovary and uterus, and give further support to the view put forward in our previous paper that these actions of danazol may contribute to its therapeutic effects. PMID- 1618271 TI - Influence of a long-acting bradykinin antagonist, Hoe 140, on some acute inflammatory reactions in the rat. AB - We studied the influence of Hoe 140, a bradykinin antagonist, on inflammatory reactions induced in rats. Hoe 140 reduced paw oedema induced by bradykinin alone, bradykinin plus prostaglandin (PG) E1, carrageenan, urate crystals or urate crystals plus captopril. The inhibitory effect of Hoe 140 lasted for at least 4 h. Hoe 140 also reduced plasma exudation in sponges implanted in the back of the rat. However it did not modify paw oedema induced by zymosan or by heating the paw at 55 degrees C for 30 s. Carrageenan oedema developed to a small extent in kininogen-deficient rats while the swelling induced by heating the paw of kininogen-deficient rats was the same as that measured in normal animals. Hoe 140 had no effect on the slight swelling induced by carrageenan in kininogen deficient rats. We conclude that the kinin system is involved in inflammatory reactions induced by carrageenan, urate crystals, sponge implantation but not by zymosan and scalding. PMID- 1618272 TI - Stereoselective antimuscarinic effects of 3-quinuclidinyl atrolactate and 3 quinuclidinyl xanthene-9-carboxylate. AB - The relative affinity and selectivity of the stereoisomers of 3-quinuclidinyl atrolactate (QNA) and the enantiomers of 3-quinuclidinyl xanthene-9-carboxylate (QNX) for the pharmacologically defined muscarinic receptor subtypes was determined using functional responses of rabbit vas deferens (M1), guinea pig atria (M2) and bladder detrusor muscle (M3). All the stereoisomers behaved as competitive antagonists yielding the same rank order of potency at each receptor subtype: (RR)-QNA greater than (RS)-QNA greater than (SR)-QNA greater than (SS) QNA and (R)-QNX greater than (S)-QNX. Moreover, the eudismic ratios relative to (RR)-QNA for (RS)-, (SR)- and (SS)-QNA, respectively, ranged from 4 to 308 at all three subtypes. Stereoselective effects were also observed for QNX; (S)-QNX/(R) QNX ratios ranged from 76 to 248. In contrast, there was a distinct lack of receptor selectivity among the isomers of QNA and QNX for either the M1, M2 or M3 muscarinic receptor subtypes. Stereoselective effects were also evident in vivo in the guinea pig cystometrogram, where the rank order of potency of the isomers of QNA and QNX was similar to that observed in vitro. (RR)-QNA and (R)-QNX equipotently depressed intravesical bladder pressure (PvesP) (ID50 = 0.06 mg/kg i.v.). Other parameters (bladder capacity, threshold pressure) were unaltered by the stereoisomers. The data demonstrate that despite the high affinity of the eutomers of QNA and QNX for muscarinic receptors, they discriminate poorly among muscarinic subpopulations, thus limiting their utility to subclassify muscarinic receptors. PMID- 1618273 TI - Similarity between the vasorelaxing activity of dinitrosyl iron cysteine complexes and endothelium-derived relaxing factor. AB - Dinitrosyl iron complexes with cysteine (DNIC) induced a concentration-dependent relaxation of pre-contracted (norepinephrine, 10(-7) M) de-endothelialized ring segments of rat aorta. The vasodilator response was more similar to acetylcholine (ACh)-induced relaxation in intact aortic rings than to nitric oxide (NO)-induced relaxation. The time course of tone recovery after maximal concentrations (10(-5) M) of DNIC was similar to the time course of tone recovery after endothelium dependent relaxation induced by ACh, whereas the restoration of tone after NO was much faster. Vessel tone was restored by oxyhemoglobin (10(-5) M) in all cases. The results suggest that DNIC with cysteine may function as endothelium-derived relaxing factor in the vessels. PMID- 1618274 TI - Release of endothelin in the oleic acid-induced respiratory distress syndrome in rats. AB - Rats injected intravenously with oleic acid developed pulmonary edema leading to hypoxia and hypercarbia. These changes were accompanied by an increase in immunoreactive endothelin (ir-ET) in plasma as early as 15 min after injection. At 45 min after injection plasma levels peaked at 114 +/- 19 pg/ml plasma (n = 8) and reached basal levels again after 240 min. In contrast, much larger amounts of ir-ET were found in the bronchoalveolar lavage fluid, with a peak at 120 min (2878 +/- 258 pg/lung, n = 7) preceding the maximum hypoxia observed at 180 min. In both plasma and bronchoalveolar lavage fluid samples ir-ET was characterized by reverse-phase HPLC as a mixture consisting mainly of ET-1 and smaller amounts of big ET-1, ET-2 and ET-3. In light of the biological effects of ET, the data suggest that these peptides might be of pathophysiological significance in this model of adult respiratory distress syndrome. PMID- 1618275 TI - Analysis of the antagonistic actions of HOE 140 and other novel bradykinin analogues on the guinea-pig ileum. AB - The type of antagonism exhibited by three novel bradykinin (BK) antagonists, D Arg-[Hyp3,Thi5,D-Tic7,Oic8]BK (HOE 140, compound I), D-Arg-[Hyp3,D-Tic7,Oic8]BK (compound II) and [Arg(Tos)1,Hyp3,Thi5,D-Tic7,Oic8]BK (compound III), was compared with that of a conventional antagonist, D-Arg-[Hyp2,Thi5,8,D-Phe7]BK (compound IV), on the guinea-pig ileum. The novel compounds induced rightward displacements of cumulative concentration-response curves to BK, accompanied by a progressive reduction of the maximum effect (Emax) without a significant decrease in the slope, whereas no reduction of Emax was observed with compound IV. Actions of substance P on the guinea-pig ileum and of vasopressin on the rat uterus remained completely unaffected. It is concluded that as the novel BK analogues show competitive as well as non-competitive inhibition in the guinea-pig ileum, but the inhibition is reversible and specific, they are dual antagonists. PMID- 1618276 TI - Role of intracellular Na+ activity in the negative inotropy of strophanthidin in cardiac Purkinje fibers. AB - The relation between intracellular sodium activity (aNai) and different phases of strophanthidin inotropy was studied in sheep cardiac Purkinje fibers superfused in vitro. Strophanthidin (1 microM) progressively increases aNai whereas increases and then decreases contractile force, induces contracture ('mechanical toxicity') and arrhythmias ('electrical toxicity'). Contractile force begins to decrease at approximately 11 mM aNai. Force and aNai show a positive correlation during the increasing and a negative correlation during the decreasing phase of strophanthidin inotropy. In high [K]o (8, 12 and 16 mM), strophanthidin increases aNai and force to a smaller peak and fails to induce toxicity. In high [Na]o (+18.5%), strophanthidin increases aNai and force to a larger peak and induces electrical toxicity below and mechanical toxicity above a higher aNai value (approximately 15 mM). In higher [K]o, high [Na]o restores the ability of strophanthidin to induce mechanical toxicity. Thus, mechanical toxicity begins when aNai increases past a critical value and the continuing aNai increase correlates with decrease in contractile force and contracture. The critical value of aNai is modified by Ca load related to changes in membrane potential or to Na electrochemical gradient. PMID- 1618277 TI - Different radiant heat intensities differentiate intracerebroventricular morphine from beta-endorphin-induced inhibition of the tail-flick response in the mouse. AB - The antinociceptive effects of morphine and beta-endorphin given intracerebroventricularly (i.c.v.) or intrathecally (i.t.) were evaluated by inhibition of the tail-flick and hot-plate paw-licking responses evoked by three different intensities of heat stimulation (low, intermediate and high) in male ICR mice. Morphine given i.c.v. was more potent in inhibiting the tail-flick response evoked by low than high intensity of heat stimulus. beta-Endorphin given i.c.v., on the other hand, was equally potent in inhibiting the tail-flick response evoked by different intensities of heat. This differential effect of morphine and beta-endorphin was not shown when morphine and beta-endorphin were given i.t. Morphine and beta-endorphin given i.c.v. or i.t. were equally potent in inhibiting the paw-licking response at different intensities of hot-plate temperature. Our results suggest that morphine given i.c.v. may inhibit high intensity heat-evoked tail-flick response spinally and inhibits low intensity heat-evoked tail-flick response supraspinally. Our results also provide additional evidence for different neural mechanisms of antinociceptive action of morphine and beta-endorphin. PMID- 1618278 TI - Development of tolerance to the anticonvulsant effect of vigabatrin in amygdala kindled rats. AB - The anticonvulsant, adverse and biochemical effects of the novel antiepileptic drug vigabatrin (gamma-vinyl GABA), which increases GABA (gamma-aminobutyric acid) levels by inhibition of the GABA degrading enzyme GABA aminotransferase, were examined in amygdala-kindled rats after acute and chronic administration. Vigabatrin proved to be a potent anticonvulsant drug at acute doses (100-200 mg/kg), but during chronic administration, the anticonvulsant activity of the treatment was lost already in the second week of treatment. Tolerance also developed to the adverse effects, i.e. hypothermia, sedation and motor impairment. Determination of vigabatrin in plasma indicated that tolerance was not due to declining drug levels. Furthermore, determination of endogenous amino acids in plasma showed that GABA levels were highly elevated throughout the period of treatment, although the extent of GABA accumulation decreased in the second week. After cessation of chronic treatment with vigabatrin, there was no clear indication of withdrawal symptoms, except a prolonged seizure or afterdischarge duration in experiments with 100 mg/kg per day. The data suggest that chronic treatment with vigabatrin may be associated with a loss of anticonvulsant efficacy, at least when the drug is given as monotherapy. PMID- 1618279 TI - Evidence for a saturable, energy-dependent and carrier-mediated uptake of oral antidiabetics into rat hepatocytes. AB - The hepatic uptake of two sulfonylureas, glisoxepide and glibenclamide, was investigated in isolated rat hepatocytes. Two transport processes were defined: passive physical diffusion and saturable carrier transport. For diffusion at pH 7.4 the permeability coefficients were 3.3 x 10(-6) cm/s for glisoxepide and 10.6 x 10(-6) cm/s for glibenclamide. Saturable uptake differed among the sulfonylureas. Glibenclamide uptake was neither energy- nor sodium-dependent and temperature dependence was linear. The apparent activation energy for saturable glibenclamide uptake was 15.2 kJ/mol and Q10 values for uptake between 7 and 37 degrees C were 1.17 +/- 0.12. Saturable glibenclamide uptake exhibited a Km = 3.1 microM and a Vmax = 416 pmol/mg cell protein per min. Thus glibenclamide uptake was defined kinetically as a facilitated diffusion process. Glisoxepide uptake revealed two Km values: Km1 = 2-3 microM and Vmax1 = 200 pmol/mg protein per min, and Km2 = 110 microM and Vmax2 = 1600 pmol/mg protein per min. Uptake at low and high substrate concentration was energy-dependent, sodium-dependent and was inhibited by ouabain. Temperature dependence increased markedly beyond 22 degrees C and the apparent activation energy was 59.7 kJ/mol at low Km1 glisoxepide concentrations and 60.3 kJ/mol at high Km2 concentrations. Whereas glisoxepide was slowly taken up into AS-30D hepatoma cells, glibenclamide was not. The hepatic uptake of glibenclamide was not inhibited by glisoxepide but glibenclamide inhibited glisoxepide uptake. The inhibition by glibenclamide was noncompetitive. Isolated hepatocytes accumulated the sulfonylureas markedly and metabolized both. The metabolized radioligands were slowly released into the incubation buffer. The results indicate that the hepatic uptake of the two sulfonylureas is by carrier-mediated transport. The uptake processes are, however, strikingly different, indicating heterogeneity of sulfonylurea transporters. PMID- 1618280 TI - Interaction of sulfonylureas with the transport of bile acids into hepatocytes. AB - The sulfonylurea compounds glisoxepide and glibenclamide inhibit the uptake of bile acids into isolated rat hepatocytes. The Ki values for the inhibition of cholate uptake was 9 microM with glibenclamide and 200 microM with glisoxepide. The inhibition of cholate uptake by both sulfonylureas was noncompetitive. Uptake of the conjugated bile acid taurocholate was inhibited by glibenclamide, Ki = 75 microM. Again the inhibition was noncompetitive. Glisoxepide inhibited taurocholate uptake only in the absence of sodium ions. Under sodium-free conditions glisoxepide also strongly inhibited cholate uptake. The inhibition was competitive, Ki = 42 microM. Both bile acids interfered with the hepatocellular uptake of [3H]glisoxepide, with IC50 values of 375 and 467 microM for cholate and taurocholate, respectively. The uptake of [3H]glibenclamide was inhibited by cholate, IC50 = 328 microM, but not by taurocholate. Glisoxepide uptake was further inhibited by blockers of the hepatocellular monocarboxylate transporter, by the loop diuretic bumetanide, by 4,4'-diisothiocyano-2,2'-stilbenedisulfonate (DIDS) and by sulfate. Glibenclamide uptake was weakly inhibited by DIDS and by anthracene-9-carboxylic acid (A-9-C) but not by bumetanide and sulfate. Neither bromosulfophthalein nor the fatty acid oleate inhibited glisoxepide or glibenclamide uptake. These results are consistent with the transport of glisoxepide via the transport system for the unconjugated bile acid cholate. Glibenclamide uptake is mediated by a still unknown hepatocellular transport system. PMID- 1618281 TI - Inhibitory effect of inaperisone hydrochloride (inaperisone), a new centrally acting muscle relaxant, on the micturition reflex. AB - We examined the effects of inaperisone hydrochloride (inaperisone), a new centrally acting muscle relaxant, on bladder function in anesthetized rats and isolated rat tissues. We also investigated its mechanism of action. When a balloon inserted into the bladder was expanded, rhythmic bladder contractions were observed; inaperisone (4 mg/kg i.v.) abolished these contractions, in both normal and decerebrated rats. The bladder tonus or bladder contraction induced by peripheral stimulation of the pelvic nerve was barely inhibited by inaperisone (4 mg/kg i.v.), but this dose of inaperisone abolished the efferent discharge from the pelvic nerve that accompanied the rhythmic bladder contractions. The doses of intracerebroventricularly (i.c.v.) and intrathecally injected inaperisone which abolished the rhythmic bladder contractions were 10 and 100 micrograms, respectively. The inhibitory effects of inaperisone (4 mg/kg i.v.) were not diminished by naloxone (1 mg/kg i.v.) or by bicuculline (0.5 mg/kg i.v.), but were diminished by phaclofen (30 mg/kg i.v. or 300 micrograms i.c.v.). The specific binding of [3H]baclofen to rat brain synaptosomal membranes was barely inhibited by inaperisone (up to 1 mM). From these results, it is speculated that, among other possible mechanisms, inaperisone inhibits the micturition reflex by acting indirectly on GABAB receptors in the brainstem. PMID- 1618282 TI - The anti-parkinsonian drug amantadine inhibits the N-methyl-D-aspartic acid evoked release of acetylcholine from rat neostriatum in a non-competitive way. AB - The anti-viral drug amantadine is used in the treatment of Parkinson's disease without the drug having a well established mechanism of action. Amantadine is reported to displace the non-competitive NMDA receptor antagonist MK-801 from its binding site in the central nervous system. We show that amantadine inhibits, in a non-competitive way, the NMDA receptor-mediated stimulation of acetylcholine release from rat neostriatum in vitro in 'therapeutic' (i.e. low micromolar range) concentrations. Moreover, contrary to previous reports, amantadine, in this concentration range, did not affect the in vitro release of dopamine from neostriatal tissue. PMID- 1618283 TI - Endothelin-1 release from the mesenteric arteries of cyclosporine-treated rats. AB - The release of endothelin-1 from mesenteric arteries from cyclosporine-treated rats was measured by a specific enzyme immunoassay after purification of the perfusate on an immunoaffinity column. Mesenteric arteries from cyclosporine treated rats (25 mg/kg per day for 6 weeks) released a significantly larger amount of endothelin-1 than arteries from vehicle-treated control rats (P less than 0.05). Serum creatinine levels were not significantly different in the two groups. These findings indicate that cyclosporine is a potential inducer of endothelin release from the mesenteric artery. PMID- 1618284 TI - Quantitative light microscopic demonstration of increased pallidal and striatal met5-enkephalin-like immunoreactivity in rats following chronic treatment with haloperidol but not with clozapine: implications for the pathogenesis of neuroleptic-induced movement disorders. AB - Acute and late onset movement disorders frequently complicate the treatment of psychosis with typical neuroleptic drugs like haloperidol, but not with atypical neuroleptic drugs like clozapine. Although the neural mechanisms underlying neuroleptic-induced movement disorders remain unknown, alterations in basal ganglia function are likely involved. A potential role for the endogenous opiate peptides in neuroleptic-induced movement disorders is suggested by the immunocytochemical localization of met5-enkephalin (ME) in the striatopallidal projection pathway, and by the increased levels of ME measured by radioimmunoassay in the rat caudate-putamen nuclei (CPN) following haloperidol treatment. We sought to determine whether met5-enkephalin-like immunoreactivity (MELI) in terminal fields within globus pallidus and in perikarya in CPN was differentially altered in rats chronically treated with haloperidol or clozapine. Acrolein-fixed forebrain sections were collected from cohorts of adult rats receiving 21-day oral administration of haloperidol, clozapine, or water. Sections from the three treatment groups were collectively processed for immunocytochemical labeling using varying dilutions of ME antiserum and the avidin-biotin peroxidase method. In globus pallidus, densitometry measures revealed significantly increased levels of immunoperoxidase labeling for ME in haloperidol-treated, but not in clozapine-treated animals. In CPN, optical densitometry as well as cell counting measurements also showed a significant increase in MELI only in the haloperidol-treated group. These results support the concept that alterations in endogenous opiate peptides in basal ganglia may contribute to movement disorders seen in patients receiving typical neuroleptic drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618285 TI - Responses in the CA1 region of the rat hippocampus to a noxious stimulus. AB - We report here some physiological and pharmacological characteristics of noxious stimuli-induced changes in the hippocampal CA1 pyramidal cell synaptic excitability to field CA3 stimulation. A noxious heat stimulus applied to the left hind paw (LHP) produced a persistent depression of the CA1 population spike (PS) which habituated to a repetition of the stimulus. Interestingly, exposure of the tail to a noxious stimulus following habituation of the LHP produced a depression of the CA1 PS. This finding suggested that persistent depression and habituation are topographically represented. In separate experiments we determined that while the persistent depression of the CA1 population spike was accompanied by, in most cases, a prolonged increase in the amplitude of the CA1 antidromic field potential, there was a concurrent persistent depression and habituation of the CA1 PS and the corresponding apical dendritic field excitatory postsynaptic potential (dfEPSP). This suggested that noxious stimulus-induced CA1 synaptic depression is mediated at the apical dendritic region, perhaps postsynaptically at the dendrites and/or presynaptically on CA3 afferent terminals. Furthermore, atropine sulfate (40 mg/kg ip), which prevented the depression of the CA1 PS, also blocked the depression of dfEPSP when iontophoresed at the apical dendritic recording site. In addition atropine antagonized the depression of the dfEPSP produced by iontophoretic acetylcholine (Ach) but not gamma-aminobutyric acid. However, iontophoretic atropine at the cell body recording site did not prevent the depression of the CA1 PS. These results are consistent with the notion that Ach release in the apical dendrites of CA1 pyramidal cells following a noxious stimulus depresses CA1 synaptic excitability. PMID- 1618286 TI - Immune system of the spontaneously hypertensive rat. I. Sympathetic innervation. AB - Extensive bidirectional interactions are believed to exist between the sympathetic nervous system and the immune system. The spontaneously hypertensive rat (SHR) is known to possess both increased sympathetic nervous system activity with increased tissue catecholamine levels in several peripheral organs and a moderate T lymphocyte immune deficiency. We examined the development of innervation in both primary (thymus) and secondary (spleen) organs of the immune system of the SHR compared to immunocompetent Wistar-Kyoto (WKY), Fisher 344 (F 344), and Long Evan (LE) rats from birth through 24 weeks. Using glyoxylic acid induced histofluorescence to visualize monoaminergic nerve fibers, coded specimens were examined and morphologically evaluated for the extent and distribution of innervation. The innervation of the SHR thymus was significantly increased at 2 and 12 weeks of age over the other strains. Unlike the control strains, splenic innervation in SHR was delayed until 2 weeks of age when it suddenly became exuberant. At 12 weeks, the innervation of the SHR spleen was increased over all control strains. By 24 weeks the innervation had regressed to a level comparable to the levels of the other rat strains in these tissues. During the suckling period, the size (weight) of the WKY spleen was larger and the level of innervation was decreased compared to the other strains. These strain-related differences in the development of sympathetic innervation of thymus and spleen likely reflect the complex, bidirectional interplay between the nervous and the immune systems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618287 TI - A morphological and morphometric analysis of the optic nerve in the hypothyroid rat. AB - This investigation was designed to morphologically evaluate the effects of hypothyroidism on the development of myelin and axons in the rat optic nerve. Four pups from each group of normal and propylthiouracil-induced hypothyroid rats were sacrificed at 14, 21, 28, and 35 postnatal days. Optic nerves were studied by both light and electron microscopes. The hypothyroid animals had significantly reduced body and brain weights compared to those of their age-matched controls. In the hypothyroid animals, the cross-sectional area of the optic nerve, the fiber density, and fiber occupancy were significantly diminished compared to those of the controls. The mean individual fiber size was unaffected. However, the relationship between the total axonal area to myelin thickness was similar in the control and experimental groups, implying that the feedback mechanism between myelinating cells and axons was not affected by hypothyroidism. Thus, this study indicates that the principal insult of neonatal hypothyroidism results in a delay in myelin acquisition of myelinated fibers, resulting in diminished cross sectional area of the optic nerve, fiber density, and fiber occupancy. PMID- 1618288 TI - Fate of B1-B2 and B3 rhombencephalic cells transplanted into the transected spinal cord of adult rats: light and electron microscopic studies. AB - Embryonic cell suspensions (14-day embryos) containing either B3 or B1-B2 serotonergic cell groups were obtained by microdissection of specific rhombencephalic regions and transplanted into the transected spinal cord of adult male Sprague-Dawley rats. After 3 months of survival, the animals were sacrificed and the spinal cords processed for the immunocytochemical detection of serotonin (5-HT). 5-HT-immunoreactive fibers from B1-B2-grafted cells were selectively distributed in the ventral horn and the intermediolateral cell column (IML) where they established conventional synaptic contacts. However, B3 5-HT cells grew and extended their processes into the dorsal horn where in addition we observed scarce synaptic contacts as in the normal spinal cord. These results suggest that the specificity of the 5-HT innervation of the spinal cord by grafted neurons is due, at least partly, to the presence of local mechanisms mediating guidance and cell recognition, possibly operating in conjunction with preexisting substrate pathways. PMID- 1618289 TI - The stimulatory effect of magnetic fields on regeneration of the rat sciatic nerve is frequency dependent. AB - The effects of exposure to sinusoidal magnetic fields on regeneration of the rat sciatic nerve were studied. Regeneration distances were measured after a crush lesion. The rats were exposed to a 0.1-mT magnetic field of various frequencies (50-2000 Hz) inside a pair of Helmholtz coils for various periods of time. Regeneration was measured by the pinch test or by immunocytochemical staining for neurofilaments 3, 4, or 6 days after the lesioning. Frequencies of 250, 500, and 1000 Hz significantly increased the regeneration distance. Higher (2000 Hz) and lower (50 Hz) frequencies had no effect. Maximal stimulation was obtained at 1000 Hz. At this frequency the rate of regeneration was increased by 24%. The results suggest that a broad frequency window exists within which the regeneration processes are sensitive to perturbation by magnetic fields and/or currents induced in the animal. PMID- 1618290 TI - Induction of dendritic spine proliferation by an astrocyte secreted factor. AB - A number of neuron-supporting functions have been ascribed to astrocytes. In this study we found that a proliferation of Purkinje cell dendritic spines, a target site for presynaptic axon terminals, was induced in cytosine arabinoside-treated cerebellar cultures by exposure to astrocyte-conditioned medium. This result suggests that astrocytes may instigate the elaboration of postsynaptic neuronal elements prior to the appearance of axons. This may be an important mechanism in neural development, postdevelopmental neuroplastic change, or regeneration. PMID- 1618291 TI - Amitriptyline produces analgesia in the formalin pain test. AB - A dose of 20 mg/kg of amitriptyline reduced pain in the second phase of the formalin test, which is an animal model of long-lasting pain in humans. Since the analgesic effect was produced by a single dose, which is insufficient to produce an antidepressant effect, these results indicate that amitriptyline has analgesic properties that are independent of its antidepressant properties. PMID- 1618292 TI - New mRNA probes for hippocampal responses to entorhinal cortex lesions in the adult male rat: a preliminary report. AB - Three new mRNA responses were found in the hippocampus of the adult male rat after entorhinal cortex lesions (ECL) that induce synaptic reorganization. Hippocampus cDNA libraries were screened by a subtractive hybridization strategy designed to detect ECL-induced mRNAs. Partial sequencing showed clones with similarities to mouse vimentin, ferritin, and polypeptide 7B-2. A sequence similar to mouse SNAP-25 sequence was also detected. Using a mouse SNAP-25 probe, rat SNAP-25 mRNA increased in the hippocampus after ECL. PMID- 1618293 TI - alpha-Amylases and approaches leading to their enhanced stability. AB - The recent state of the knowledge of properties and structure of alpha-amylases is reviewed with the aim of elucidation the basis for their stabilization. Three principal ways for obtaining stable alpha-amylases (isolation of enzymes from extremophiles, production of extremophilic enzymes in mesophiles, and modification of mesophilic enzymes) are discussed separately. Detailed experimental examples are given for modification approaches. PMID- 1618294 TI - HSP70-related 65 kDa protein of beet yellows closterovirus is a microtubule binding protein. AB - Beet yellows virus (BYV) genome encodes a 65 kDa protein homologous to the HSP70 family of cellular heat-shock proteins (Agranovsky, A.A., Boyko, V.P., Karasev, A.V., Koonin, E.V. and Dolja, V.V. (1991) J. Mol. Biol. 217, 603-610). The respective gene was cloned and expressed in vitro yielding a product of the expected size (p65). This product was found to bind to the purified microtubules with a binding constant of 4 x 10(-7) M. The binding of p65 was stimulated if ATP presented in the translation mixture was hydrolyzed by apyrase. Removal of the short C-terminal domains of alpha- and beta-tubulin by subtilisin digestion abolished the binding, demonstrating its specificity. The possible role of p65 association with microtubules in the movement of virus within and/or between plant cells is proposed. PMID- 1618295 TI - Correlation between local cell membrane displacements and filterability of human red blood cells. AB - Local mechanical fluctuations of the cell membrane of human erythrocytes were shown to involve MgATP- and Mg(2+)-driven fast membrane displacements. We propose that these local bending deformations of the cell membrane are important for cell passage through capillaries. In order to verify this hypothesis, we examined cell membrane fluctuations and filterability of erythrocytes over a wide range of medium osmolalities (180-675 mosmol/kg H2O). The results indicate the existence of a positive correlation between the amplitude of local cell membrane displacements and cell filterability. We suggest that the occurrence of metabolically driven membrane displacements on the side surface of the red blood cell diminishes its bending stiffness and enables it to fold more efficiently upon entrance into blood capillaries. Thus, local cell membrane displacements seem to play an important role in microcirculation. PMID- 1618296 TI - On the catalytic mechanism of EcoRI and EcoRV. A detailed proposal based on biochemical results, structural data and molecular modelling. AB - EcoRI and EcoRV have a very similar active site, as is apparent from a comparison of the structures of their respective protein-DNA complexes. Based on structural and mechanistic data, as well as detailed molecular modelling presented here, a mechanism for the DNA cleavage by these enzymes is suggested in which the attacking water molecule is activated by the phosphate group 3' to the scissile phosphodiester bond, and in which the leaving group is protonated by a water molecule associated with the essential cofactor, Mg2+. The mechanism proposed may also apply to other nucleases. PMID- 1618297 TI - A modified Kex2 enzyme retained in the endoplasmic reticulum prevents disulfide linked dimerisation of recombinant human insulin-like growth factor-1 secreted from yeast. AB - The majority of the recombinant human insulin-like growth factor-1 (IGF1) molecules, secreted from yeast using the prepro sequence of the prepro-alpha factor, are not active monomers but inactive, disulfide-linked dimers. The prepro sequence of the prepro-alpha-factor, usually referred to as the alpha-factor leader (alpha FL), consists of a pre or signal sequence and a proregion. After signal sequence removal during translocation into the endoplasmic reticulum (ER) the proregion is still attached to IGF1 when it folds to acquire a tertiary structure. Mature IGF1 is released only in a late Golgi compartment by the membrane-bound endoprotease Kex2p. We find that co-expression of a novel ER retained Kex2p variant, soluble Kex2pHDEL, can prevent intermolecular disulfide bond formation between two IGF1 molecules, implying that the presence of the proregion during the folding of IGF1 in the ER could be a reason for disulfide linked dimerisation. This result indicates that the proregion of the alpha FL may have a role in the folding of some heterologous proteins in yeast, and that the ER-retained Kex2p mutant could be used as a convenient tool to study the cellular function of the proregions present naturally in various eucaryotic precursor proteins. PMID- 1618298 TI - Identification of reactive tyrosine residues in cysteine-reactive dehydrogenases. Differences between liver sorbitol, liver alcohol and Drosophila alcohol dehydrogenases. AB - Modification of tyrosine residues with tetranitromethane and reversible sulphite protection of cysteine residues were tested on three dehydrogenases of two families. In liver alcohol dehydrogenase no Tyr residue is appreciably labelled, while in the homologous sorbitol dehydrogenase Tyr-109 is specifically labelled; the difference corresponds to a segment correlating with subunit interactions and the different quaternary structures of the proteins. In Drosophila alcohol dehydrogenase, Tyr modification is multiple, and the results show the presence of two different states of Cys residues, reactive in the presence and absence of cupric ions, respectively. Super-activation with cyanide was also noticed after S sulphocysteine protection. The results demonstrate the possibility of identification of specific Tyr residues in proteins with reversibly protected Cys residues. PMID- 1618299 TI - Two-way cleavage of beta-amyloid protein precursor by multicatalytic proteinase. AB - The beta-amyloid protein (beta-AP) derived from a beta-amyloid protein precursor (APP) is a hallmark of Alzheimer's disease. The abundant generation of beta-AP suggests the abnormal processing of APP, but the molecular mechanism remains unclear. The main APP-processing enzyme was purified from the rat brain and identified to be a macropain-like multicatalytic proteinase. The purified enzyme cleaved the Gln15-Lys16 bond of beta-AP, but altered to cleave at the N-terminus of beta-AP to release the extracellular domain of beta-AP in the presence of Ca2+. These findings suggest that the functional change in this multicatalytic proteinase may result in abnormal processing of APP. PMID- 1618300 TI - Detection of a new mutant alpha-1-antichymotrypsin in patients with occlusive cerebrovascular disease. AB - A new mutant alpha-1-antichymotrypsin (variant ACT) was found by direct sequencing and PCR-single strand conformation polymorphism (PCR-SSCP). This variant ACT was a point mutation of exon V of ACT, with the substitution of Met by Val. Four out of six individuals with this variant ACT had occlusive cerebrovascular disease, leading to one hypothesis that there might be an association between this mutation and occlusive-cerebrovascular disease. PMID- 1618302 TI - Exon-intron organization of the Arabidopsis thaliana protein kinase genes CDC2a and CDC2b. AB - We have previously shown by cDNA cloning that a higher plant, Arabidopsis thaliana, possesses at least two CDC2 genes (CDC2a and CDC2b) similar to the cell cycle-controlling cdc2 gene of Schizosaccharomyces pombe. To understand the exon intron organization of these genes, genomic clones were isolated and their nucleotide sequences determined. The coding and 5'-untranslated regions of CDC2a were interrupted by seven and one introns, respectively, whilst CDC2b contained three introns within the coding portion. These intron positions partly overlapped with each other and with those of the yeast cdc2 gene, nevertheless the lengths and sequences of the corresponding introns were diverse. PMID- 1618301 TI - Group II phospholipase A2 induced by interleukin-1 beta in cultured rat gingival fibroblasts. AB - Previously, we reported the presence of group II-like phospholipase A2 activity in the soluble fraction of rat gingiva. In the present study, we found that treatment of rat gingival cells with human recombinant interleukin-1 beta resulted in dose-dependent stimulation of intracellular and extracellular phospholipase A2 activity. Antisera against group II phospholipase A2 totally blocked the interleukin-1 beta-induced phospholipase A2 activity, but antisera against group I phospholipase A2 did not. Moreover, immunoblot analysis showed that the induced phospholipase A2 was group II phospholipase A2. These findings suggest that the induced enzyme belongs to the group II phospholipase A2 family of proinflammatory enzymes. PMID- 1618303 TI - Conversion of 5,6-dihydroxyeicosatetraenoic acids. A novel pathway for lipoxin formation by human platelets. AB - Leukotriene A4 may be metabolized to 5(S),6(R)- and 5(S),6(S)-dihydroxy-7,9-trans 11,14-cis-eicosatetraenoic acids by enzymatic or non-enzymatic hydrolysis. Incubation of human platelet suspensions with these dihydroxy acids led to the formation of lipoxin A4 and 6(S)-lipoxin A4 via lipoxygenation at C-15. Furthermore, human platelets converted the two 5(R),6(S)- and 5(R),6(R)-dihydroxy 7,9-trans-11,14-cis-eicosatetraenoic acids to tetraene-containing trihydroxyeicosatetraenoic acids. In contrast, leukotrienes C4, D4 and E4 were not transformed to cysteinyl-lipoxins. Time-course studies of leukotriene A4 metabolism in human platelet suspensions indicated lipoxin formation via two pathways: (i) direct conversion of leukotriene A4, leading to formation of the lipoxin intermediate 15-hydroxy-leukotriene A4; and (ii) 15-lipoxygenation of the 5(S),6(R)- and 5(S),6(S)-dihydroxyeicosatetraenoic acids. The results demonstrate that lipoxygenation at C-15 of 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acids may be an alternative novel pathway for platelet-dependent lipoxin formation. PMID- 1618304 TI - Involvement of separate domains of the cellulosomal protein S1 of Clostridium thermocellum in binding to cellulose and in anchoring of catalytic subunits to the cellulosome. AB - Fragments of the 250 kDa S1 subunit of the Clostridium thermocellum cellulosome were obtained by protease-induced or spontaneous degradation. All detectable fragments, down to a mass of about 30 kDa, retained the ability to bind to 125I labelled endoglucanase CelD, one of the catalytic subunits of the cellulosome. Several fragments were able to bind both to cellulose and to CelD. However, some fragments that could still bind to CelD did not have the ability to bind to cellulose. Therefore, S1, a putative scaffolding protein of the cellulosome, is likely to carry two separate types of domains, one of which binds to cellulose, while the other type binds to the various catalytic subunits of the complex. PMID- 1618305 TI - Relationship of neural cell adhesion molecules (N-CAMs) with adenylate cyclase. AB - Bovine brain cDNA cloned earlier and attributed to calmodulin-independent adenylate cyclase encodes the neural cell adhesion molecule (N-CAM). The expression of N-CAM mRNA in Xenopus laevis oocytes increases their basal adenylate cyclase activity. Polyclonal antibodies against synthetic peptide A, VAENQQGKSKAAHFV (664-678 amino acid residues of bovine N-CAM), containing sequence AXXXXGKS which is homologous to the nucleotide-binding consensus sequence GXXXXGKS, inhibit the adenylate cyclase activity. A close relationship appears to exist between adenylate cyclase and N-CAM. PMID- 1618306 TI - Autophagic degradation of peroxisomes in isolated rat hepatocytes. AB - Degradation of the peroxisomal enzymes fatty acyl-CoA oxidase and catalase was studied in hepatocytes isolated from rats treated with clofibrate and from control rats. Hepatocytes were incubated in the absence of amino acids in order to ensure maximal flux through the autophagic pathway and in the presence of cycloheximide to inhibit protein synthesis. (1) Degradation of the two peroxisomal enzymes in hepatocytes from clofibrate-fed rats, but not in hepatocytes from control rats, was much faster than that of other intracellular enzymes. This increased degradation of the peroxisomal enzymes was almost completely prevented by 3-methyladenine, an inhibitor of macroautophagic sequestration. (2) The increased degradation of the peroxisomal enzymes was also inhibited by a long-chain (C16:0) and a very-long-chain (C26:0) fatty acid, but not by C12:0, a medium-chain fatty acid, or by C8:0, a short-chain fatty acid. These results provide direct evidence for the proposal that autophagic sequestration can be highly selective [(1987) Exp. Mol. Pathol. 46, 114-122]. It is concluded that preferential autophagy of peroxisomes is prevented when these organelles are supplied with their fatty acid substrates. PMID- 1618307 TI - Transcription efficiency of human apolipoprotein A-I promoter varies with naturally occurring A to G transition. AB - In human, the gene coding for apolipoprotein A-I (apo A-I), a protein of the plasma lipid transport system, is expressed only in the liver and the intestine. A naturally occurring A to G substitution in the promoter at position -78 was shown to be associated with high density lipoproteins (HDL) in females. We have studied the effect of this mutation on promoter activity using various lengths of promoter sequences and the CAT reporter gene system. Transient expression studies after introduction of these constructs into Hep 3B cells revealed that in the region spanning -330 to +1 of the promoter an A to G substitution increases the activity approximately twofold. On the other hand, when further upstream region ( 1469 to +397) is also included, the promoter activity seems comparable in both alleles. Our results show how minimal sequence variations can affect the in vitro analysis of promoter activity. PMID- 1618308 TI - Coordinate regulation of murein peptidase activity and AmpC beta-lactamase synthesis in Escherichia coli. AB - In the periplasmic space of Escherichia coli, the (L)-m-A2pm-(D)-m-A2pm peptide, the lipoprotein, and the AmpC beta-lactamase are controlled by growth rate. To explain this coordinate regulation, it is proposed that the AmpC protein functions as an LD-endopeptidase in addition to its known function as a beta lactamase. As LD-peptides, DD-peptides and beta-lactams are structurally similar, LD-peptidases may belong to the larger family of DD-peptidases and serine beta lactamases. In contrast to E. coli, many related bacteria possess an inducible AmpC protein. Several gene systems necessary for AmpC induction are known to affect various aspects of peptidoglycan metabolism. It is proposed that AmpC induction occurs indirectly via a recyclable cell wall peptide. PMID- 1618309 TI - Characterisation of a chloroplast-encoded secY homologue and atpH from a chromophytic alga. Evidence for a novel chloroplast genome organisation. AB - secY is a prokaryotic gene that encodes the SecY protein, an integral membrane component of the prokaryotic protein translocation apparatus. A chloroplast encoded secY homologue has been identified in the unicellular, chromophytic alga, Pavlova lutherii. The gene predicts a protein composed of ten membrane-spanning regions, that is approximately 25% homologous and 50% similar to bacterial and plastid SecY proteins. The secY gene from P. lutherii is independent of the ribosomal protein (rp) gene cluster to which it is closely linked in other organisms. In P. lutherii secY is located 5' to atpI and atpH. Since, in higher plants the atpIHFA gene cluster and the rp gene cluster are separated by approximately 50 kb, we conclude, this indicates a novel chloroplast gene arrangement in P. lutherii. PMID- 1618310 TI - Inositol trisphosphate-induced hyperpolarization in rat dorsal root ganglion neurons. AB - Inositol 1,4,5-trisphosphate (1,4,5-InsP3) was perfused into rat dorsal root ganglion (DRG) neurons by whole-cell patch-clamp electrodes, while measuring the membrane potential. This operation evoked a transient (2-3 min) membrane hyperpolarization of about -15 mV (from -42 mV) followed by a depolarization. The membrane hyperpolarization was abolished when 30 mM EGTA was perfused together with 1,4,5-InsP3 or when 0.2 mM quinine was added to the bath solution. The hyperpolarizing response was enhanced when a low-Ca2+ EGTA-free intracellular solution was used. Two InsP2 isomers induced a different response. Our results suggest that the hyperpolarization is due to 1,4,5-InsP3-induced Ca2+ release which may trigger Ca-sensitive K+ channels to open. Present results show that cultured DRG neurons are able to respond to 1,4,5-InsP3 perfusion in the whole cell configuration. PMID- 1618311 TI - Correlation between carbohydrate-binding specificity and amino acid sequence of carbohydrate-binding regions of Cytisus-type anti-H(O) lectins. AB - A carbohydrate-binding peptide of the di-N-acetylchitobiose-binding Cytisus sessilifolius anti-H(O) lectin I (CSA-I) was isolated from the endoproteinase Asp N digest of CSA-I by affinity chromatography on a column of N-acetyl-D glucosamine oligomer-Sepharose (GlcNAc oligomer-Sepharose). The amino acid sequence of the carbohydrate-binding peptide of CSA-I was determined to be DTYFGKTYNPW using a gas-phase protein sequencer. This sequence corresponds to the sequence from Asp-129 to Trp-139 based on the primary structure of CSA-I, and shows a high degree of homology to those of the putative carbohydrate-binding peptide of the Laburnum alpinum lectin I (LAA-I) (DTYFGKAYNPW) and of the Ulex europaeus lectin II (UEA-II) (DSYFGKTYNPW). The binding of these three anti-H(O) lectins is known to be inhibited by di-N-acetylchitobiose but not by L-fucose. These results strongly suggest that there is a good correlation between the carbohydrate-binding specificity and the amino acid sequence of the carbohydrate binding regions of di-N-acetylchitobiose-binding lectins. PMID- 1618312 TI - Photoinduced degradation of the D1 protein in isolated thylakoids and various photosystem II particles after donor-side inactivations. Detection of a C terminal 16 kDa fragment. AB - Photoinduced degradation of the photosystem II (PSII) reaction center D1 protein was studied in isolated thylakoids and different PSII subparticles. A 16 kDa fragment corresponding to the C-terminus of the protein is detected in thylakoids when they are inactivated at the donor side before illumination. The same D1 fragment is found in different types of PSII preparations at different integration levels characterized by different polypeptide compositions so long as they have an inactivated donor side and an active electron acceptor for the reduced pheophytin. However, when the PSII particle is equal to or smaller than the 43-less PSII core complex, other fragments are observed which are not found in more integrated systems. PMID- 1618313 TI - IL-2-dependent in vivo and in vitro tyrosine phosphorylation of IL-2 receptor gamma chain. AB - We previously reported a molecule, p64, which was tentatively named the gamma chain, coprecipitable with the beta chain of human interleukin-2 receptor (IL 2R). The present study demonstrated that the gamma chain, as well as the beta chain expressed on IL-2-responsive cells, is phosphorylated on tyrosine residues in an IL-2-dependent manner in vivo and in vitro. The in vivo tyrosine phosphorylation of both chains was similarly induced within 1 min after IL-2 stimulation, and their in vitro tyrosine phosphorylation with the anti-IL-2R beta antibody-directed immunocomplex was also increased by treatment of cells with IL 2. These results suggest that a tyrosine kinase is associated with the beta gamma subunit complex, of which activation by IL-2 may result in transduction of intracellular signals. PMID- 1618314 TI - Purification and primary structure of murine cryptdin-1, a Paneth cell defensin. AB - We have purified and determined the amino acid sequence of cryptdin-1, a murine Paneth cell defensin. The peptide corresponds to a previously characterized mRNA that accumulates to high abundance during postnatal ontogeny of the small bowel. Acid-extracted intestinal protein was fractionated by cation-exchange chromatography and fractions were assayed for antimicrobial activity. One peak of anti-Salmonella activity contained a putative defensin, based on its predicted electrophoretic migration in acid-urea PAGE. The peptide was purified to homogeneity by RP-HPLC and sequenced. These studies demonstrate defensin expression in non-myeloid tissue. The N-terminal extension of cryptdin-1 is a unique structural feature of this novel epithelial defensin. PMID- 1618315 TI - Natural abundance 15N NMR assignments delineate structural differences between intact and reactive-site hydrolyzed Cucurbita maxima trypsin inhibitor III. AB - 15N NMR assignments were made to the backbone amide nitrogen atoms at natural isotopic abundance of intact and reactive-site (Arg5-Ile6) hydrolyzed Cucurbita maxima trypsin inhibitor III (CMTI-III and CMTI-III*, respectively) by means of 2D proton-detected heteronuclear single bond chemical shift correlation (HSBC) spectroscopy, utilizing the previously made sequence-specific 1H NMR assignments (Krishnamoorthi et al. (1992) Biochemistry 31, 898-904). Comparison of the 15N chemical shifts of the two forms of the inhibitor molecule revealed significant changes not only for residues located near the reactive-site region, but also for those distantly located. Residues Cys3, Arg5, Leu7, Met8, Cys10, Cys16, Glu19, His25, Tyr27, Cys28 and Gly29 showed significant chemical shift changes ranging from 0.3 to 6.1 ppm, thus indicating structural perturbations that were transmitted throughout the molecule. These findings confirm the earlier conclusions based on 1H NMR investigations. PMID- 1618316 TI - Increase in protein kinase C activity is associated with human fibroblast growth inhibition. AB - Protein kinase C (PKC) activity and DNA synthesis were measured in human fetal bone marrow fibroblasts following treatment with tumor necrosis factor alpha (TNF alpha) (500 U/ml) or conditioned media containing natural cell proliferation inhibitor (CM-NCPI). Treatment with TNF alpha led to growth stimulation (120 +/- 7% of control in 24 h, 141 +/- 6% in 72 h). At the same time particulate PKC activity diminished, reaching 55 +/- 8% of control in 24 h and remaining at this level at 72 h. CM-NCPI treatment of the cells resulted in a decrease in DNA synthesis (by 39 +/- 6% in 2 h, by 58 +/- 5% in 24 h, and by 78 +/- 8% in 72 h). This was accompanied by a significant rise in particulate PKC activity which increased over 3-fold in 2 h, over 5-fold in 24 h, and up to 11-fold in 72 h. This 11-fold elevation was maintained after 2 week exposure of the fibroblasts to CM-NCPI. The PKC inhibitor neomycin abolished CM-NCPI induced growth inhibition, whereas PKC activator 12-O-tetradecanoylphorbol 13-acetate intensified it. These results suggest that CM-NCPI acts as PKC activator and that negative growth regulation by extracellular agents may involve stimulation of PKC activity. PMID- 1618317 TI - Baculovirus expression of mammalian G protein alpha subunits. AB - Complementary DNAs encoding three subtypes of the alpha subunit (alpha i-1, alpha o and alpha s) of rat guanyl nucleotide regulatory proteins were used to construct recombinant baculoviruses which direct high-level expression of the corresponding proteins in cultured Sf9 insect cells. The expressed proteins were recognized by polyclonal antisera specific for the different alpha chains, and co migrated with the native proteins from rat brain membranes in immunoblotting analyses. Soluble and particulate forms of all three immunoreactive alpha chains were observed following ultracentrifugation of cell lysates. Biosynthetic radiolabelling of infected cells with [35S]methionine or [3H]myristate showed that both soluble and particulate forms of alpha i-1 and alpha o were myristoylated; in contrast, alpha s did not incorporate myristate. The soluble fractions from cells expressing alpha chains showed high levels of GTP-binding activity over that observed in uninfected cells, or in cells infected with wild type virus. The peak expression levels observed at 72 h post-infection were highest for alpha o at ca. 400 pmol of GTP-gamma-35S/mg protein, or roughly 2% of the total soluble protein. The results of this work show that the baculovirus system can be employed for high-level production of mammalian G protein alpha chains which retain GTP-binding activity and are appropriately modified by myristoylation. PMID- 1618318 TI - Purification of the MglC/E membrane proteins of the binding protein-dependent galactose transport system of Salmonella typhimurium. AB - The high affinity galactose transport system of Salmonella typhimurium consists of four proteins, a periplasmic galactose binding protein (the MglB protein), and three inner membrane-associated proteins, the MglA, MglC and MglE proteins. We purified the MglC/E proteins from an MglC/E hyperproducing strain after solubilisation of inclusion bodies in guanidine hydrochloride followed by renaturation in a detergent-containing buffer and affinity chromatography on a MglB-Sepharose column. The MglC/E proteins are devoid of ATPase activity and they complement an extract from a strain carrying a plasmid with the mglA gene for reconstitution of the MglB-dependent galactose transport in proteoliposomes. PMID- 1618319 TI - GTP-binding proteins in luminal and basolateral membranes from pars convoluta and pars recta of rabbit kidney proximal tubule. AB - The GTP-binding proteins on luminal and basolateral membrane vesicles from outer cortex (pars convoluta) and outer medulla (pars recta) of rabbit proximal tubule have been examined. The membrane vesicles were highly purified, as ascertained by electron microscopy, by measurements of marker enzymes, and by investigating segmental-specific transport systems. The [35S]GTP gamma S binding to vesicles, and to sodium cholate-extracted proteins from vesicles, indicated that the total content of GTP-binding proteins were equally distributed on pars convoluta, pars recta luminal and basolateral membranes. The membranes were ADP-ribosylated with [32P]NAD+ in the presence of pertussis toxin and cholera toxin. Gel electrophoresis revealed, for all preparations, the presence of cholera toxin [32P]ADP-ribosylated 42 and 45 kDa G alpha s proteins, and pertussis toxin [32P]ADP-ribosylated 41 kDa G alpha i1, 40 kDa G alpha i2 and 41 kDa G alpha i3 proteins. The 2D electrophoresis indicated that Go's were not present in luminal nor in basolateral membranes of pars convoluta or pars recta of rabbit proximal tubule. PMID- 1618320 TI - The kinetics of a two-state transition of myosin subfragment 1. A temperature jump relaxation study. AB - Temperature-jump measurements were carried out on myosin subfragment 1 (S1) labeled at Cys-707 with 5-(iodoacetamido)fluorescein (S1-AF). The relaxation was monitored by following the increase in the fluorescence intensity of the attached probe after a jump of 5.8 degrees C. A single relaxation process was observed over a range of final temperatures, and the relaxation time decreased from 16.69 ms at 15 degrees C to 3.91 ms at 27 degrees C. The relaxation results are interpreted in terms of a two-state transition: (S1-AF)L K+ in equilibrium with K (S1-AF)H, and the observed single relaxation time (tau) equals l/(k(+) + k-). The individual first-order rate constants, k+ and k-, were calculated from tau and the equilibrium constant previously determined. The activation energy was 21.9 kcal/mol for the forward reaction and 9.3 kcal/mol for the reverse reaction, corresponding to an enthalpy value of 12.6 kcal/mol for the two-state transition. The results provide, for the first time, direct kinetic evidence of a two-state transition of S1 in the absence of bound nucleotide, and support a two-state model of unliganded myosin subfragment 1. PMID- 1618321 TI - Quantitative analysis of dystrophin in fast- and slow-twitch mammalian skeletal muscle. AB - The relative tissue content of dystrophin has been evaluated in the slow-twitch soleus (primarily type I fibers) and fast-twitch vastus lateralis (primarily type IIb fibers) muscles of the rat and mouse, as well as in human biopsy samples from the vastus lateralis and gluteus maximus muscles, using a sensitive immunochemical assay. The dystrophin content of the soleus muscle was approximately twofold higher than in the vastus lateralis muscle. This difference is not entirely explained by the higher total sarcolemmal surface of the smaller soleus muscle type I fibers, and is therefore attributed to a higher content of dystrophin in the type I fibers compared to type IIb fibers. PCR analysis of the dystrophin transcript levels in the two muscle types indicated no significant differences. Analysis of human muscle biopsies revealed a twofold higher dystrophin content in the vastus lateralis muscle compared to the gluteus maximum muscle. It is concluded that the tissue content of dystrophin may vary significantly among physiologically different skeletal muscle types. PMID- 1618322 TI - Cyclosporin A protects hepatocytes subjected to high Ca2+ and oxidative stress. AB - Hepatocytes incubated with 0.8 mM t-butylhydroperoxide are protected by cyclosporin A when the medium Ca2+ concentration is 10 mM, but not when it is 2.5 mM. The highest Ca2+ level is associated with an inhibition of t butylhydroperoxide-dependent malondialdehyde accumulation and with mitochondrial Ca2+ loading within the cells. These findings are new evidence that t butylhydroperoxide can kill cells by peroxidation-dependent and -independent mechanisms, and suggest that the mitochondrial permeability transition and the resultant de-energization are components of the peroxidation-independent mechanism. Cyclosporin A may have considerable utility for the protection of cells subjected to oxidative stress. PMID- 1618323 TI - Inhibitors of polyamine biosynthesis affect the expression of genes encoding cytoskeletal proteins. AB - The polyamines are ubiquitous components of mammalian cells. Those compounds have been postulated to play an important role in different cellular functions including the reorganization of cytoskeleton associated with the cell cycle. In the studies reported here, it was found that inhibitors of polyamine biosynthesis, methylglyoxal-bis[quanylhydrazone] (MGBG) and difluoromethylornithine (DFMO), prevent mitogen-induced accumulation of mRNAs encoding major cytoskeletal components, beta-actin and alpha-tubulin, in mouse splenocytes. These findings suggest mechanisms through which polyamines may exert their effects on the cytoskeleton integrity. PMID- 1618324 TI - The identification and characterisation of an actin-binding site in alpha-actinin by mutagenesis. AB - We have shown previously that the N-terminal actin-binding domain of alpha actinin retains activity when expressed in E. coli as a fusion protein with glutathione-S-transferase. In the present study we have made a series of N- and C terminal deletions within this domain and show that an actin-binding site is contained within residues 120-134. Amino acid substitutions within this region indicate that several highly conserved hydrophobic residues are involved in binding to F-actin. The hypothesis that the interaction between alpha-actinin and F-actin is predominantly hydrophobic in nature is supported by the observation that binding is relatively independent of salt concentration. PMID- 1618325 TI - A protein factor extracted from murine brains confers physiological Ca2+ sensitivity to exocytosis in sea urchin eggs. AB - Exocytosis in sea urchin eggs can be reconstituted in vitro using the cell ghosts (the isolated cortices). When the isolated cortices were handled in the medium primarily composed of non-chaotropic ions, exocytosis can be induced by a micromolar level of Ca2+. However, when the cortices are exposed to chaotropic anions such as Cl-, it is induced only at higher Ca2+ concentrations of 10(-5) to 10(-4) M, due to the chaotropic anionic effect, by which a specific protein(s) is dissociated from the cortex. The dissociated protein can be added back to the cortex to restore the original Ca2+ sensitivity [(1984) Dev. Biol. 101, 125-135]. A protein which has the similar effect on the isolated cortex was also found in the extract of murine brain. This protein was neither calmodulin, a G-protein or a kinase. The data suggest the general regulatory mechanism of the Ca2+ sensitivity of exocytosis by a protein factor widely distributed among cells. PMID- 1618326 TI - Acidic pH induces fusion of cells infected with baculovirus to form syncytia. AB - The enveloped baculovirus insect cell system has been used extensively for expression of recombinant proteins, including viral fusion proteins. We tested wild-type baculovirus for endogenous fusion protein activity. Syncytia formation, dye transfer, and capacitance changes were observed after incubating infected Spodoptera frugiperda cells in acidic media, consistent with fusion protein activity. Only a short acidic pulse of 10 s is needed to trigger syncytia formation. Identical results were obtained with recombinant baculovirus. This new system is convenient for studying pH activated cell-cell fusion. However, using this enveloped virus to study the mechanism of recombinant fusion proteins requires caution. PMID- 1618327 TI - Identification of DEBS 1, DEBS 2 and DEBS 3, the multienzyme polypeptides of the erythromycin-producing polyketide synthase from Saccharopolyspora erythraea. AB - The ery A region of the erythromycin biosynthetic gene cluster of Saccharopolyspora erythraea has previously been shown to contain three large open reading frames (ORFs) that encode the components of 6-deoxyerythronolide B synthase (DEBS). Polyclonal antibodies were raised against recombinant proteins obtained by overexpression of 3' regions of the ORF2 and ORF3 genes. In Western blotting experiments, each antiserum reacted strongly with a different high molecular weight protein in extracts of erythromycin-producing S. erythraea cells. These putative DEBS 2 and DEBS 3 proteins were purified and subjected to N terminal sequence analysis. The protein sequences were entirely consistent with the and DEBS 3 proteins were purified and subjected to N-terminal sequence analysis. The protein sequences were entirely consistent with the translation start sites predicted from the DNA sequences of ORFs 2 and 3. A third high molecular weight protein co-purified with DEBS 2 and DEBS 3 and had an N-terminal sequence that matched a protein sequence translated from the DNA sequence some 155 base pairs upstream from the previously proposed start codon of ORF1. PMID- 1618328 TI - Cloning of a human choline kinase cDNA by complementation of the yeast cki mutation. AB - A human choline kinase cDNA was cloned by complementation of the yeast choline kinase mutation, cki, from a human glioblastoma cDNA expression library. The deduced sequence of the human enzyme comprised 456 amino acids with a calculated relative molecular mass of 52,065. The human enzyme resembled the rat liver enzyme over the entire sequence. It also resembled the yeast enzyme in the carboxy-terminal region, but not much in the amino-terminal region. PMID- 1618329 TI - Transcriptional activation of the gene for the large subunit of human m-calpain by 12-o-tetradecanoyl-phorbol-13-acetate. AB - The effect of the treatment of HeLa cells with a tumor-promoting phorbol ester, 12-o-tetradecanoyl-phorbol-13-acetate (TPA) on the expression of the genes for the calpain family has been examined. Among the mRNAs for the calpain family, only the mRNA for the large subunit of human m-calpain (calpain mL) was specifically induced by treatment of cells with TPA, suggesting its specific function in response to cellular stimuli. The effect of TPA on the expression of the calpain mL gene was further examined using fusion genes containing the promoter/enhancer region of the calpain mL gene fused upstream of the bacterial chloramphenicol acetyltransferase (CAT) gene, showing that the promoter/enhancer sequence of the calpain mL gene contains a cis-acting element which responds to TPA and activates transcription of the downstream sequence. PMID- 1618330 TI - Zwitterionic amphiphiles that raise the bilayer to hexagonal phase transition temperature inhibit protein kinase C. The exception that proves the rule. AB - We synthesized the zwitterionic amphiphile cholesterylphosphorylethylpyridinium. This substance activated protein kinase C (PKC) in a micelle-based assay, but in a vesicle assay it was inhibitory. An analog of this compound, in which the pyridine ring is saturated and the nitrogen methylated, showed similar behaviour with PKC. Replacing cholesterol by an aliphatic alcohol lowered the extent of activation in the micelle assay. These results demonstrate that, with some membrane additives, the vesicle and micelle assays give opposite results. Results from the membrane-based vesicle assay for PKC are in accord with the generalization that zwitterionic amphiphiles that raise the bilayer to hexagonal phase transition temperature in model membranes are inhibitors of PKC. PMID- 1618331 TI - Fluorescence studies on the interaction of adenine with ricin A-chain. AB - Ricin A-chain, an N-glycosidase that attacks 28S rRNA at a highly conserved adenine residue, has a unique tryptophan (Trp-211) in the putative active site cleft. Fluorescence spectroscopy revealed that specific binding of adenine to the A-chain caused a large enhancement of Trp-211 fluorescence (70%) and a concomitant red shift of the emission spectrum (8 nm). A Scatchard plot of the fluorescence enhancement data was not linear, indicating that the environment of Trp-211 was altered by heterogeneous binding of adenines. These results, taken together with the protective effect of adenine on the ribosome-inactivation by ricin A-chain, suggest that at least two adenines bind to the active site cleft. PMID- 1618332 TI - The Euglena gracilis rbcS gene contains introns with unusual borders. AB - We have recently shown that, in Euglena gracilis, leader sequences are transferred by trans-splicing to the vast majority of cytoplasmic mRNAs. Trans splicing is involved in the maturation of the rbcS transcript, which encodes eight small subunits of the ribulose 1,5 bisphosphate carboxylase/oxygenase. In this report, we show that the Euglena rbcS gene introns are different from introns found in plant rbcS genes. In addition these introns do not have the conserved 5' and 3' border sequences found in introns of eucaryotic nuclear encoded pre-mRNAs, and they do not present any homology with self-splicing introns of groups I and II. Secondary structure analyses show that the 5' and 3' ends of Euglena introns can base-pair, suggesting that an unusual splicing mechanism exists in Euglena. PMID- 1618333 TI - Identification of cholesterol-bound aldehydes in copper-oxidized low density lipoprotein. AB - Lipid-soluble cholesteryl ester core aldehydes (aldehydes still bound to the cholesterol ring) were identified among the products of copper-catalyzed peroxidation of human low density lipoprotein (LDL). The LDL was exposed to oxygenated buffer and 5 microM CuSO4 for 24 h. The core aldehydes were isolated as the dinitrophenylhydrazones, and were identified by reverse-phase HPLC with mass spectrometry. The major components were the C4-C10 oxoalkanoyl esters of cholesterol and 7-ketocholesterol, and accounted for 1-2% of the cholesteryl linoleate and arachidonate consumed. PMID- 1618334 TI - Is bupivacaine a decoupler, a protonophore or a proton-leak-inducer? AB - This paper deals with the mechanism of bupivacaine uncoupling of oxidative phosphorylation in rat heart mitochondria. By comparison with the effects of QX 572, a permanently charged quaternary amine-type local anesthetic, it is concluded that the effects of bupivacaine and QX 572 may be explained by classical uncoupling behaviour. In the case of bupivacaine this uncoupling effect is mediated through a protonophore-like mechanism, whereas that of QX 572 is simply explained by an electrophoretic uptake. PMID- 1618335 TI - Yeast ADP/ATP carrier (AAC) proteins exhibit similar enzymatic properties but their deletion produces different phenotypes. AB - Saccharomyces cerevisiae strains expressing a single type of ADP/ATP carrier (AAC) protein were prepared from a mutant in which all AAC genes were disrupted, by transformation with plasmids containing a chosen AAC gene. As demonstrated by measurements of [14C]ADP specific binding and transport, all three translocator proteins, AAC1, AAC2 and AAC3 when present in the mitochondrial membrane, exhibited similar translocation properties. The disruption of some AAC genes, however, resulted in phenotypes indicating that the function of these proteins in whole cells can be quite different. Specifically, we found that the disruption of AAC1 gene, but not AAC2 and AAC3, resulted in a change in colony phenotype. PMID- 1618336 TI - Biological activity of bovine placental lactogen in 3T3-F442A preadipocytes is mediated through a somatogenic receptor. AB - Bovine placental lactogen (bPL) exhibited antimitogenic differentiation-promoting biological activity in 3T3-F442A preadipocytes. Competitive binding studies and affinity labelling revealed bPL activity to be mediated through a somatogenic type of receptor that recognizes human growth hormone (hGH) and bovine GH, but not ovine prolactin or human PL. The bioactivity of bPL was sixfold lower than that of hGH despite that bPL is binding to the somatogenic receptors with fivefold higher affinity. This discrepancy may result from the relatively low ability of bPL to induce post-receptoral effects such as receptor dimerization. PMID- 1618337 TI - 1H NMR study on the conformation of bacitracin A in aqueous solution. AB - The conformation of bacitracin A, a widely used cyclic dodecapeptide antibiotic in aqueous solution, has been investigated using 500 MHz 1H NMR and molecular modeling. Findings revealed that a region (residues 1-6) is folded over the cyclic ring, resulting in metal coordination sites, a thiazoline ring, and Glu4 and His10 being proximate to each other. PMID- 1618338 TI - Cloning and expression of a glycine transporter from mouse brain. AB - We have isolated a cDNA clone from a mouse brain library encoding the glycine transporter (GLYT). Xenopus oocytes injected with a synthetic mRNA accumulated [3h]glycine to levels of up to 80-fold above control values. The uptake was specific for glycine and dependent on the presence of Na+ and Cl- in the medium. The cDNA sequence predicts a highly hydrophobic protein of 633 amino acids with 12 potential transmembrane helices. The predicted amino acid sequence has 40-45% identity to the GABA, noradrenaline, serotonin and dopamine transporters. This implies that all of these neurotransmitter transporters may have evolved from a common ancestral gene that diverged into the GABA, glycine and catecholamine subfamilies at nearly the same time. PMID- 1618339 TI - Synthesis and characterization of a 29-amino acid residue DNA-binding peptide derived from alpha/beta-type small, acid-soluble spore proteins (SASP) of bacteria. AB - A 29-amino acid residue peptide (SASP-peptide) derived from the sequence of the putative DNA-contacting portion at the carboxyl terminus of an alpha/beta-type small, acid-soluble spore protein (SASP) of Bacillus subtilis has been synthesized by automated solid-phase methods and tested for its ability to interact with DNA. Circular dichroism (CD) spectroscopy reveals an interaction between this SASP-peptide and DNA, both by an increase in alpha-helix content of the peptide (which alone has a mostly random conformation) and by enhancement of the 275-nm CD band of the DNA. In contrast to results with intact alpha/beta-type SASP, however, the peptide does not induce a B----A conformational transition in the DNA. The SASP-peptide also binds to poly(dG).poly(dC) and protects this polynucleotide against DNase I digestion and UV light-induced cytosine dimer formation, parallel to findings made previously with native alpha/beta-type SASP. The results confirm the hypothesis that the carboxyl-terminal region of the alpha/beta-type SASP directly contacts DNA and possesses some, but not all, of the functional characteristics of the intact molecule. PMID- 1618340 TI - Measurement of GTP gamma S binding to specific G proteins in membranes using G protein antibodies. AB - We developed a novel method to quantitatively measure GTP gamma S binding to specific G proteins in crude membranes using G-protein antibodies. The basic strategy was that the materials were initially incubated with [35S]GTP gamma S at 37 degrees C. After 4 degrees C incubation in the wells of an ELISA plate precoated with G-protein antibodies, the radioactivity of each well was counted. This method, using an anti-Gi antiserum and an anti-Gs antiserum, quantitatively and specifically detected the binding of GTP gamma S to purified Gi2 and Gs. In S49 cell membranes, GTP gamma S binding to immunoreactive Gs was observed in a time-dependent manner that obeyed first-order kinetics, and the rate constant was stimulated approximately twofold in response to isoproterenol. The effect of isoproterenol was not observed in unc mutant membranes. The present method thus makes it possible to quantitatively measure GTP gamma S binding to specific G proteins in cell membranes. PMID- 1618341 TI - Targeting efficiencies of various permutations of the consensus C-terminal tripeptide peroxisomal targeting signal. AB - Two types of peptide signals are known to independently target proteins into the peroxisomal matrix. One of these is a consensus C-terminal tripeptide which is conserved in many microbody proteins derived from diverse species. The second signal is an N-terminal sequence found in a small subset of peroxisomal proteins. We have tested 18 possible variants of the consensus tripeptide targeting signal for their ability to facilitate the transport of a cytosolic passenger protein, chloramphenicol acetyltransferase, into peroxisomes of monkey kidney cells. Our results reveal the presence of a hierarchy of preferred amino acid substitutions at each position of the tripeptide. PMID- 1618342 TI - Calcium administration stimulates the expression of calcium-binding protein regucalcin mRNA in rat liver. AB - The distribution and expression of mRNA encoding the Ca(2+)-binding protein regucalcin in rats were investigated by Northern blot analyses. Liver regucalcin cDNA (0.6 kb) was used as a probe. The analyses of total RNAs extracted from various tissues of rat indicated that regucalcin mRNA was mainly present in liver but only slightly in kidney with a size of 1.8 kb. The expression level decreased with increasing age (3, 10 and 25 weeks). A single intraperitoneal administration of calcium chloride (15 mg Ca/100 g body weight) induced a remarkable increase in regucalcin mRNA in liver; the level was about 200% of control at 30 min after the administration. Subsequently, the expression level began to decrease with time and was about 40% of control level at 120 min after the administration. The increase in regucalcin mRNA levels at 30 min after calcium administration was dose-dependent. These observations show that the expression of regucalcin mRNA is specific in liver of various tissues, and that it is regulated by Ca2+ administration. Regucalcin may have a role as regulatory protein for calcium homeostasis in liver cells. PMID- 1618343 TI - Oxidized low density lipoproteins elicit DNA fragmentation of cultured lymphoblastoid cells. AB - Lymphoblastoid cell lines continuously pulsed with mildly oxidized low density lipoproteins, exhibited a significant increase of DNA fragmentation induced by oxidized LDL internalized by cells. DNA fragmentation was associated with an increasing number of morphologically characteristic apoptotic cells simultaneously with the increase of cytotoxicity indexes, and the activation of the poly(ADP-ribose) polymerase, a nuclear enzyme stimulated by DNA strand breaks. The potential involvement of these biochemical and morphological changes in atherogenesis is discussed. PMID- 1618344 TI - Nucleotide composition of genes and hydrophobicity of the encoded proteins. AB - We find that true proteins are generally more hydrophobic than the corresponding hypothetical proteins encoded by the randomized gene nucleotide sequences. Furthermore, the protein hydrophobicity but not its gene nucleotide composition is conserved within evolutionary families of functionally related proteins. These two findings indicate that there is a general drift to modify gene nucleotide composition in the course of evolution. An inspection of codon usage in genes shows that the drift mainly increases the content of adenine at the expense of thymine. PMID- 1618345 TI - Heat-labile enterotoxin crystal forms with variable A/B5 orientation. Analysis of conformational flexibility. AB - A new native crystal form of heat-labile enterotoxin (LT) has two AB5 complexes in the asymmetric unit with different orientations of the A subunit with respect to the B pentamer. Comparison with other crystal forms of LT shows that there is considerable conformational freedom for orientating the A subunit with respect to the B pentamer. The rotations of A in different crystal forms do not follow one specific axis, but most of them share a hinge point, close to the main interaction area between A and B5. Analysis of the two high-resolution structures available shows that these rotations cause very little change in the actual interactions between A and B5. PMID- 1618346 TI - Phosphoramidon-sensitive endothelin-converting enzyme in vascular endothelial cells converts big endothelin-1 and big endothelin-3 to their mature form. AB - Incubation of big endothelin-3 (big ET-3(1-41)) with the membrane fraction obtained from cultured endothelial cells (ECs) resulted in an increase in immunoreactive-ET (IR-ET). This increasing activity was markedly suppressed by phosphoramidon, which is known to inhibit the conversion of big ET-1(1-39) to ET 1(1-21). Reverse-phase HPLC of the incubation mixture of the membrane fraction with big ET-3 revealed one major IR-ET component corresponding to the elution position of synthetic ET-3(1-21). When the cultured ECs were incubated with big ET-3, a conversion to the mature ET-3, as well as an endogenous ET-1 generation, was observed. Both responses were markedly suppressed by phosphoramidon. By the gel filtration of 0.5% CHAPS-solubilized fraction of membrane pellets of ECs, the molecular mass of the proteinase which converts big ET-1 and big ET-3 to their mature form was estimated to be 300-350 kDa. Phosphoramidon almost completely abolished both converting activities of the proteinase. We conclude that the above type of phosphoramidon-sensitive metalloproteinase functions as an ET converting enzyme to generate the mature form from big ET-1 and big ET-3 in ECs. PMID- 1618347 TI - Fibronectin type III-like sequences and a new domain type in prokaryotic depolymerases with insoluble substrates. AB - Fibronectin type III-like sequences are present in many proteins from higher eukaryotes and are involved in protein-protein interactions, heparin binding and cell adhesion. A nine-member family of bacterial sequences is shown to be significantly homologous to the type III-like sequences. All the sequences are contained in secreted depolymerases acting on complex, energy-rich insoluble substrates, in which they apparently do not participate in catalysis or substrate binding, their exact function remaining unclear. Furthermore, a new family of sequences, present in some cellulases, is presented. PMID- 1618348 TI - More on pay and play physician contribution to health care reform. PMID- 1618349 TI - Video-assisted thoracic surgery: our first 20 cases. AB - Video-assisted thoracic surgery has been performed in 20 patients at the Medical Center of Delaware. Operations included seven pulmonary wedge resections, one mediastinal procedure, and 12 pleural procedures. In all cases, a definitive diagnosis was made or the lesion was removed. One postoperative atypical pneumonia occurred. One patient whose wedge resection proved to be squamous cell carcinoma on frozen section underwent a formal thoracotomy and lobectomy. Estimated savings in the eight patients who formerly would have undergone a thoracotomy incision is estimated at $30,000 for room cost alone. We foresee a markedly expanded role for this technique in major pulmonary resections, esophageal procedures, and cardiac surgery in the near future. PMID- 1618350 TI - When a doctor plays judge. PMID- 1618351 TI - And so much for arbitration. PMID- 1618352 TI - Wake up call--get involved. PMID- 1618353 TI - Photoaffinity labeling of an acorn barnacle lectin with a photoactivatable fluorescent reagent derivative of D-galactosamine. AB - A photoactivatable D-galactosamine derivative was prepared by reaction of the amino group of D-galactosamine with 1-azide-5-naphthalene sulfonyl chloride (ANS Cl). The derivative (GalN-ANS) inhibited the agglutination activity of an acorn barnacle lectin against rabbit erythrocytes to the same extent as D galactosamine. We used GalN-ANS for photoaffinity labeling of the lectin. The photolabeled lectin was digested with pronase and the digest was separated by reversed-phase high-performance liquid chromatography by monitoring fluorescence and uv absorption to isolate the peptide labeled with GalN-ANS. Amino acid analyses of the labeled peptides revealed that GalN-ANS preferentially covalently labeled two regions in the carbohydrate recognition domain of the lectin. One of them was the highly conserved amino-acid sequence region throughout all calcium dependent animal lectins. PMID- 1618354 TI - Phenol oxidase activity in hemolymph compartments of Aedes aegypti during melanotic encapsulation reactions against microfilariae. AB - Monophenol oxidase (MPO) and diphenol oxidase (DPO) activity was assessed in hemocytes, cell-free plasma and complete hemolymph collected from Aedes aegypti Liverpool strain, intrathoracically inoculated with saline alone, immune activated by the inoculation of Dirofilaria immitis microfilariae (mff), and uninoculated. Enzyme activities between groups were compared using a radiometric hydroxylation assay (MPO) and a high pressure liquid chromatography with electrochemical detection assay (DPO). There were no significant differences in enzyme activity in hemocytes, cell-free plasma, and complete hemolymph between uninoculated and saline-inoculated controls. Both MPO and DPO activity of mosquito hemocytes and complete hemolymph from immune-activated mosquitoes were significantly increased at 12 and 24 h postinoculation as compared with the enzyme activity from saline-inoculated mosquitoes, but no significant increase in enzyme activity was detected in cell-free plasma from immune-activated mosquitoes. Increases of MPO and DPO activity in hemocytes and hemolymph following immune activation were proportional, thereby suggesting that a single enzyme might react with both monophenols and o-diphenols within the hemolymph of A. aegypti. Results also suggest that augmented phenol oxidase activity associated with melanotic encapsulation reactions is associated primarily with hemocytes. PMID- 1618355 TI - Toxicity of Aeromonas salmonicida cells to Atlantic salmon Salmo salar peritoneal macrophages. AB - Several strains of Aeromonas salmonicida were toxic to cultured peritoneal macrophages of Atlantic salmon, Salmo salar, in minimum doses of 5 x 10(6) CFU, whereas other strains were not. There was no correlation between cytotoxicity and in vivo virulence of the bacteria, the presence or absence of the two major surface components of A. salmonicida (namely, the A-layer and the O polysaccharide chain of the LPS) nor, finally, with the ability of the strains to produce the following enzymes in vitro: protease, hemolysin, elastase and lecithinase. Toxicity was only observed with metabolically active bacteria and not with formalin- or heat-killed bacteria. The exact nature of the toxic factor remains unknown but is most likely associated with the surface of the bacteria. It is not extracellular since 24 and 48 h culture supernatants of the cytotoxic strains had no apparent effect on macrophages. The cytotoxic effect was found to be severe and rapid, it is likely a major virulence factor of A. salmonicida, but the exact role of such a potent toxin in the pathology of furunculosis has yet to be clarified. PMID- 1618356 TI - Stress and human reproduction. AB - The interaction between emotional stress and infertility has been investigated for many years. Many infertile couples show marked stress during infertility evaluation and treatment. Most of the investigations that were performed during the last two decades show that in the majority of cases stress is the result and not the cause of infertility. The biological interaction between stress and infertility is the result of the action of stress hormones at the brain level, especially on the hypothalamus-pituitary and on the female reproductive organs. Stress hormones such as catecholamines (adrenalin, nonadrenaline and dopamine) and the hypothalamic-pituitary-adrenal axis interact with hormones which are responsible for normal ovulatory cycles: i.e., gonadotropin releasing hormone (GnRH), prolactin, LH and FSH. Endogenous opiates and melatonin secretion are altered by stress and interfere with ovulation. Sympathetic innervation of the female reproductive system provides routes by which stress can influence fertility at the of the sex organs level. Infertility causes stress which is aggravated as time passes and the couple remains infertile. Among the causes of stress are the couple's isolation, life with unrealized potential and unborn child, disruption of day-to-day life during infertility evaluation and treatment, and the couple's feeling that they do not have control of their own lives. The IVF program is considered by many as the final step for the evaluation of the couples fertility potential, hence, couples participating in an IVF program are highly stressed, especially after a failed IVF cycle. PMID- 1618357 TI - Pregnancy-specific beta 1-glycoprotein (SP1) and its relation to fetal birth weight at term pregnancy. AB - The relation between serum levels of pregnancy-specific beta 1-glycoprotein (SP1) and actual fetal and placental weights was studied in 100 full-term pregnant women. This was compared with fetal weight determination by ultrasound. SP1 levels significantly correlated with fetal and placental weights. Its determination was found to be comparable to ultrasonography in placental fetal weight assessment, especially at the extremes of fetal weight (macrosomia and small for gestational age) where special obstetric management is warranted. PMID- 1618358 TI - Pregnancy in idiopathic aplastic anemia (report of 10 patients). AB - This paper reports on 6 patients with severe, 2 with moderate and 2 with mild aplastic anemia who had a total of 18 pregnancies after the diagnosis. All four pregnancies that occurred during the active state of severe and moderate aplastic anemias were electively terminated. Two out of 14 pregnancies that occurred during the long-term remission were electively terminated for non-medical reason, two spontaneous abortions occurred and 10 live births were seen. All offspring were healthy at follow-up. During pregnancy the circulating blood cell levels decreased in 1 out of 6 pregnancies in patients who were in remission from mild and moderate aplastic anemias, and in 4 out of 8 pregnancies in patients who were in remission from severe aplastic anemia. In all 5 cases that showed a relapse during pregnancy the remission recurred following the termination of pregnancy. The data presented suggest that aplastic anemia in long-term remission can unpredictably relapse during pregnancy, but its final outcome appears not to be affected by pregnancy. Furthermore, there is no correlation between the pre pregnancy clinical course and the events during pregnancy. The outcome of pregnancy during the remission of aplastic anemia seems beneficial, and spontaneous delivery should be preferred. PMID- 1618359 TI - Reference ranges of lipids and apolipoproteins in pregnancy. AB - In order to establish the reference ranges of lipids and apolipoproteins apoA-I and apoB in serum for different periods of pregnancy we examined 719 healthy pregnant women. 172 of them were in the first trimester, 227 in the second and 320 in the third trimester. The control group, consisting of 65 healthy nonpregnant women, was used to determine the magnitude and statistical significance of the lipid changes. All lipids and apolipoproteins apoA-I and apoB were significantly elevated during the second and the third trimesters. The most prominent change was a 2.7-fold triglyceride increase in the third trimester; in the same trimester the mean level apoB increased by 56%, total cholesterol by 43%, low-density lipoprotein (LDL) cholesterol by 36% and apolipoprotein A-I by 32%. High-density lipoprotein (HDL) cholesterol rose maximally (25%) in the second trimester. The 95th percentiles of the distributions in the second and the third trimesters are: total triglyceride: 2.87 and 4.68 mmol/l; total cholesterol: 8.24 and 9.83 mmol/l; LDL-cholesterol: 5.61 and 6.48 mmol/l; apoA-I: 2.48 and 2.61 g/l; apoB: 1.47 and 1.92 g/l. The fifth percentiles of HDL cholesterol distributions are: 1.09 in the second trimester and 1.04 in the third one. The ratios of total cholesterol to HDL-cholesterol, of LDL-cholesterol to HDL-cholesterol and apoB to apoA-I were decreased in the first trimester, without change in the second, and increased in the third trimester. These data may indicate that hyperlipidaemia of pregnancy is not atherogenic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618360 TI - Fetal motility and chronic exposure to antiepileptic drugs. AB - The potential influence of antiepileptic drugs (AEDs) on fetal CNS function was studied with respect to motility patterns. Quantitative and qualitative aspects of spontaneous fetal activity were investigated for chronic AED-exposed fetuses and controls at three intervals during pregnancy: i.e. 20, 32 and 38 weeks. Movements were observed applying real-time ultrasound. Third trimester rest activity cycles were determined according to the fetal behavioural state concept. Quantitative analysis revealed no marked differences in gross fetal motility between AED-exposed fetuses and controls. Both groups demonstrated the same developmental trend from midterm towards the third trimester. The number of trunk movements decreased, while their median duration increased. The incidence of fetal eye movements during C2F was lower for AED-exposed fetuses than for controls (significant for 38 weeks). In qualitative analysis, general movements of AED-exposed fetuses were more often labeled as suspect or abnormal than those of control fetuses (respectively, 8 out of 31 and 1 out of 20; P = 0.06). Future studies concerning chronic fetal AED-exposure and fetal CNS function should focus on qualitative rather than quantitative aspects of motility. PMID- 1618361 TI - Does labetalol influence the development of proteinuria in pregnancy hypertension? A randomised controlled study. AB - It is the development of proteinuria in pregnancy-induced hypertension which is associated with an increased perinatal mortality. There is some evidence to suggest that labetalol may diminish the amount of proteinuria in patients who have already developed proteinuric pre-eclampsia. A randomised controlled study design was used to investigate whether labetalol treatment, started when a persistent diastolic blood pressure greater than 90 mmHg was observed, influenced the subsequent development of proteinuria. One hundred and fourteen women with singleton pregnancies and hypertension in the absence of proteinuria were randomised to receive either labetalol or no antihypertensive therapy. At recruitment maternal age, blood pressure and gestation were similar in both the labetalol and control groups. There was no difference in the frequency, quantity or timing of subsequent proteinuria between treatment and control groups. Overall 34% of primigravidae and 10% of parous women developed proteinuria. Labetalol did, however, control the blood pressure in 45 of the 51 treated women (88%) within 24 h. This effect was often shortlived requiring dose escalation after 3 to 5 days in the majority of cases. Labetalol was well tolerated and no significant maternal toxicity was noted. PMID- 1618362 TI - Evidence of growth retardation in neonates of apparently normal weight. AB - The aim of this study was to examine the relationship of ponderal index (PI) and the ratio of mid-arm circumference to occipito-frontal circumference (MAC/OFC) to the delivered weight of the child. Measurements were made on 160 singleton neonates with birthweight greater than 2500 g and delivery at 37 weeks or more. Surprisingly, there was a highly significant correlation between PI and birthweight and MAC/OFC and birthweight. We conclude that: (1) values of PI must be evaluated in relation to birthweight, and not against a single absolute standard for the whole normal population; (2) measurement of PI and MAC/OFC may reveal a group of growth-retarded infants amongst infants of apparently 'normal' birthweight; and (3) this group of infants might be a target for the extra care normally accorded to the low birthweight infant. PMID- 1618363 TI - Synchronous primary malignancies of the female genital tract. AB - This study includes 29 patients with synchronous primary malignancies of the female genital tract. These patients constituted 1.7% of all genital malignancies. The most frequently observed synchronous neoplasms were those of the ovary together with the endometrium (51.7%). Most patients had early-stage and low-grade disease. Stage I disease was observed in 68.1% of patients with ovarian cancer. Patients with synchronous ovarian and endometrial cancer had a 73.3% 5-year survival rate, suggesting a favorable prognosis. PMID- 1618364 TI - A rare case of chorioamnionitis by Morganella morganii complicated by septicemia and adult respiratory distress syndrome. AB - Morganella morganii, a gram-negative bacterium, usually infects older patients with urinary catheters, but does not commonly affect pregnant women. In this report we present a case of chorioamnionitis caused by Morganella morganii. The case was complicated by a life-threatening Adult Respiratory Distress Syndrome. PMID- 1618365 TI - Have 'real' NSTs been used for fetal surveillance? PMID- 1618367 TI - Doppler velocimetry in twin pregnancy. AB - The flow velocity waveform profile in the umbilical artery was measured in 50 pairs of twins during the last week before birth. A significant association was found between high resistance indicies and occurrence of late fetal heart rate decelerations; the higher the resistance, the more frequent the decelerations. Further, the connection between high resistance in the circulation of the umbilical artery and low birth weight was confirmed. Flow velocity measurements in the umbilical artery seem to be a valuable tool in identifying twin fetuses suffering from placental insufficiency. PMID- 1618366 TI - Pelvic pain and pelvic joint instability, association with oral contraceptives. PMID- 1618368 TI - Contextual control of conflicting associations in the developing rat. AB - Two experiments examined the effects of manipulations of contextual cues on the expression of conflicting associations in 18-, 26-, and 35-day-old rats. Subjects learned to GO RIGHT in a water-filled T-maze, then were trained to reverse this position habit (GO LEFT). When the competing responses were learned in the same visual context, all age groups displayed a recency effect on a subsequent test in extinction; they behaved in accordance with the last-learned GO LEFT habit. If the competing responses were learned in different visual contexts, and testing took place in the context of the first problem, 35-day-old subjects behaved in a manner consistent with the GO RIGHT context (reduced recency). However, similarly trained 18-day-old subjects showed no evidence of a reduced recency effect. Given that 18-day-old rats are sensitive to other context manipulations, the present results suggest that the ability to "disambiguate" conflicting associations by context may depend upon the maturation of a relatively late-developing configural learning system. PMID- 1618369 TI - Variation in maternal care and individual differences in play, exploration, and grooming of juvenile Norway rat offspring. AB - Individual differences in two different forms of maternal licking, time in nest and nursing, were measured during the first 2 weeks after birth. Two treatments were imposed to reduce maternal anogenital licking (AGL): peripheral zinc sulfate to interfere with reception of pup chemosignals, and dietary saline to reduce appetite for pup urine. Both treatments reduced AGL but did not affect other maternal licking. Zinc sulfate was more effective than saline during the first week, but was somewhat less selective as it also increased time in nest. Selected behavioral patterns were measured in male and female juveniles and related by multiple regression to the behavior of their mothers. Independent of the method of manipulation, maternal AGL was a significant predictor of play and open-field defecation males and of some forms of activity in the open field in both sexes. The relationships between other maternal variables and juvenile behavior were more modest. These data demonstrate that intervening in the sensory regulation of maternal behavior can produce predictable changes in stimulation provided by the dam, thereby providing a useful means for investigating the effects of protracted differences in early stimulation in otherwise normal developmental contexts. PMID- 1618371 TI - Development of antipredator responses in snakes: V. Species differences in ontogenetic trajectories. AB - The ontogeny of antipredator responses in five species of Natricine snakes was examined. In a split-litter experiment, neonates were given a standardized defensive behavior test at 1 and/or 20 days of age. Thamnophis sirtalis and Thamnophis melanogaster showed a significant increase in both striking and fleeing from a threatening stimulus. Thamnophis butleri was not reactive in terms of striking at either age but did flee frequently at both ages. Thamnophis radix showed low rates of striking and high rates of fleeing; only fleeing increased significantly between the two tests. Nerodia rhombifer exhibited moderate rates of both striking and fleeing at both ages with no developmental effects. Subsets of most of these species tested at 40 or 60 days of age found no further developmental changes. PMID- 1618372 TI - Temperature-dependent effects of maternal separation on growth, activity, and amphetamine sensitivity in the rat. AB - This study was conducted to examine the effects of an early stressor, maternal separation, on development, arousal, and sensitivity to amphetamine in the rat. Rat pups were maternally separated at nest temperature (WARM), room temperature (COLD), or nest temperature with agitation (AGIT) for 6 hr each day from 2 to 15 days of age. A control group (CONT) remained with the mother in the nest during this time. COLD subjects were developmentally delayed and had lower body and brain weights than the other three groups into adulthood. WARM and AGIT subjects (both maternally separated at nest temperature) had significant growth delays compared to CONT, but grew more quickly than COLD subjects. COLD subjects were less active than the other maternally separated groups, and WARM and AGIT groups were more active. Activity did not differ at 28 or 75 days of age. However, adult WARM subjects were less sensitive and COLD subjects were more sensitive to amphetamine as measured by locomotor activity than CONT and AGIT subjects, who did not differ from each other. The relationship between early stress, changes in dopaminergic systems, and altered drug responsiveness are discussed in terms of the implications for the etiology of drug abuse. PMID- 1618370 TI - Neonatal 6-OHDA lesions and rearing in complex environments: regional effects on adult brain 14C-2-deoxyglucose uptake revealed by exposure to novel stimulation. AB - Behavioral and neuromorphological data have suggested at least a partial interaction between the effects of norepinephrine-depleting neonatal 6-OHDA lesions and the effects of rearing in enriched environments. The present study examined the impact of both of these early manipulations upon regional brain uptake of 14C-2-deoxyglucose (14C-2DG) in adulthood. Newborn rats received 6-OHDA (50 mg/kg s.c.) or vehicle and, after weaning at 25 days, were reared in isolated versus enriched conditions. Regional brain 14C-2DG uptake was then examined at 70 80 days of age--either in the home cage or while animals were being exposed to novel, presumably arousing, stimulation. Ninety-seven brain regions were examined in eight separate groups. Results indicated that (1) Under baseline conditions, neither neonatal 6-OHDA nor differential rearing conditions produced widespread alterations in regional brain 14C-2DG uptake profiles. An overall enrichment effect was seen on only five brain areas, with rats reared in enriched environments showing lower levels of 14C-2DG uptake (-20% to -30%) than isolated rats. Neonatal 6-OHDA produced no main effect on 14C-2DG uptake in any brain region. (2) In contrast, when 14C-2DG uptake was assessed during exposure to a novel environment, five brain areas showed differential 14C-2DG uptake in 6-OHDA treated rats, and 20 brain areas showed differential uptake in rats reared in enriched conditions. (3) No significant interaction effect on brain regional 14C 2DG uptake was observed between neonatal 6-OHDA and environmental complexity factors. These results are consistent with the notion that enduring effects of rearing and early 6-OHDA treatment may, independently, relate to a general reactivity factor. They also indicate that some effects of early neurochemical injury and subsequent experiential factors may not be apparent under normal resting conditions, but only become evident in the presence of appropriate "activating" stimulation. PMID- 1618373 TI - Regulation of murine embryonic epithelial cell differentiation by transforming growth factors beta. AB - The expression of some members of the transforming growth factor beta (TGF beta) family of genes in embryonic craniofacial tissue suggests a functional role for these molecules in orofacial development. In an attempt to ascertain a role for the TGF beta s during palatal ontogeny, murine palatal shelves were excised on gestation day (GD) 12, prior to overt epithelial differentiation, grown in organ culture under serum-free conditions and exposed to TGF beta 1 and TGF beta 2 for 18 or 42 h. Shelves were labeled with [3H]-thymidine (20 microCi/ml) during the last 4 h in culture, fixed, dehydrated, embedded in paraffin and sections stained and examined by autoradiography. Treatment of GD12 palates with TGF beta 1 and TGF beta 2 resulted in precocious cessation of medial edge epithelium (MEE) DNA synthesis followed by elimination of the MEE. In addition, this response appeared to be dose-related with higher concentrations of growth factor eliciting a more marked biological response. TGF beta treatment of homologous shelves grown in apposition also resulted in precocious fusion of apposing MEE. Thus, members of the TGF beta family, known to be synthesized by palatal MEE, appear to act in an autocrine/paracrine fashion in this tissue and are capable of regulating differentiation of embryonic palatal medial edge epithelium. PMID- 1618374 TI - [Plasmapheresis in the comprehensive treatment of autoimmune hemolytic anemia]. AB - It is shown that low volumes of plasmapheresis can be used in combined treatment of patients with autoimmune hemolytic anemia who did not respond well to the routine therapy. It is a safe detoxication method with immunocorrective, hyposensitizing action that promotes more effective transfusion of red blood cell pack and washed red blood cells, and permits a significant decrease in glucocorticosteroid doses. It has been suggested that plasmapheresis could be used at early stages of the disease treatment. PMID- 1618375 TI - [Effect of antilymphocytic globulin on immunologic parameters in children with acquired aplastic anemia]. AB - Subpopulations of rosette-forming cells were studied in lymphoid pools of peripheral blood and bone marrow of 24 children with acquired aplastic anemia, after a course of treatment with antilymphocytic globulin (ALG). After termination of the preparation transfusion a decrease in the levels of "active" T lymphocytes and cells with C3-receptors was recorded. The levels of immature T lymphocytes were found to be lowered four weeks after ALG-therapy, while other subpopulations remained within the normal. The lowering activity of immunogenesis in the bone marrow combined with hemopoietic recovery after the immunosuppressive therapy have evidenced a possible participation of immunologic mechanisms in the pathogenesis of acquired aplastic anemia in children. PMID- 1618376 TI - [Factors influencing the serum ferritin level in acute leukemia patients before chemotherapy]. AB - Serum ferritin level was studied in 158 adult patients with different forms and variants of leukemia, and it was found to be elevated in 85.4% of cases. A number of factors influencing ferritin concentration in the blood serum have been established: a high degree of serum iron deficiency, leukemic intoxication, infectious complications (pneumonia, sepsis, necrosis, etc.), hemolytic syndrome. All these factors should be taken into consideration in evaluating serum ferritin levels in acute leukemia patients. PMID- 1618377 TI - [Myocardial function and rheologic properties of blood in multiple myeloma]. AB - Echocardiographic and rheologic parameters were studied in 25 patients with multiple myeloma (MM). The lowering of the contractile function of the left ventricle myocardium was attended by disorders in blood rheologic properties characterized by increasing concentration of total protein and colloid-osmotic pressure, by a decrease in the hematocrit, red blood cell deformability, volume, and mean cell hemoglobin. It has been shown that rheologic and echocardiographic shifts play an important role in the pathogenesis of hyperviscous syndrome and in the development of circulation insufficiency in MM patients. Current corrective measures are necessary for abolishing this state. PMID- 1618378 TI - [Expression of glucocorticoid receptors and blast cell clearance in children with different variants of acute lymphoblastic leukemia]. AB - Glucocorticoid receptor (GR) levels were estimated in blast cells of 24 children with acute lymphoblastic leukemia, in different immunocytologic subvariants of the disease. No relationship was revealed between immunophenotype and GR number in blasts. It was found that the response to prednisolone therapy did not depend on the number of sites specifically bound to glucocorticoids. The response character is determined not by immunophenotype but by the initial number of blast cells in the peripheral blood (the higher blastosis, the worse response). High blastosis is probably dependent on the tumor growth rate. PMID- 1618379 TI - [Splenectomy in the treatment of chronic forms of lympholeukemia]. PMID- 1618380 TI - [Compensation-adaptation reactions of hemopoiesis-inducing microenvironment of bone marrow in stress]. AB - The time course of compensation-adaptation reactions of bone marrow hemopoiesis inducing microenvironment (HIM) was studied in F1 (CBA x C57BL/6) mice subjected to 10-hour immobilization. The number of macrophage and fibroblastoid colony forming units, committed and stem precursor stroma cells responsible for HIM transport was shown to increase in the hemopoietic tissue during adaptation syndrome. HIM activation in stress was found to be macrophage- and lymphocyte dependent process. PMID- 1618381 TI - [Natural and antibody-dependent cytotoxicity of peripheral blood lymphocytes in health and in various blood system diseases]. PMID- 1618382 TI - [Hemostatic drugs of resorptive action]. PMID- 1618383 TI - [Transfusion policy in massive obstetric blood loss]. PMID- 1618384 TI - [Transfusion therapy in beta-thalassemia and sickle-cell anemia]. PMID- 1618385 TI - Handedness and spatial ability in children: further support for Geschwind's hypothesis of "pathology of superiority" and for Annett's theory of intelligence. AB - Spatial ability of 60 left-handed and 60 right-handed school children was investigated using a battery of nine tasks. The results do not agree with Levy's (1969, 1976) theory predicting spatial inferiority of left-handed individuals. Instead, higher performance by left-handed children provided further support for Annett's (Annett & Manning, 1989) theory on intelligence and for Geschwind's (Geschwind & Galaburda, 1985) hypothesis of "pathology of superiority." The distinction of left-handed and right-handed individuals into familial and nonfamilial groups appeared to be psychologically equivocal according to our results. PMID- 1618386 TI - Hordein variation in the genus Hordeum as recognized by monoclonal antibodies. AB - The composition of the major storage protein, hordein, in wild barley species has been studied by using gel electrophoresis, Coomassie staining, and immunoblot assays. We have shown earlier that it is possible to obtain cross-reaction outside the cultivated barley, with monoclonal antibodies raised against hordeins from the barley cultivar Bomi. These antibodies have now been used to investigate the hordein composition in all species of the Hordeum genus. The results showed that polypeptides similar to the two major hordein groups of cultivated barley, the B- and C-hordeins, are produced in all wild Hordeum species, and that there are both similarities and differences between the two hordein groups. The similarities indicate a common evolutionary origin, while the distinction between B- and C-hordeins in the entire genus clearly shows that the divergence of their coding genes preceded the divergence of the Hordeum species. The presence of the same antigenic site in two different species indicates that they are evolutionarily related. Among the wild species, two rarely occurring sites were exclusively found in H. vulgare ssp. spontaneum and H. bulbosum, which confirms that they are the cultivated barley's closest relatives. Some of the antibodies also gave an extensive reaction pattern with H. murinum, which suggests a fairly close relationship to H. vulgare, though not as close as between H. vulgare and H. bulbosum. PMID- 1618387 TI - Gamma irradiation induced deletions in an alien chromosome segment of the wheat 'Indis' and their use in gene mapping. AB - Deletion mutants were produced in a translocated chromosome segment derived from Thinopyrum distichum (Thunb.) Love. Spikes of the translocation line 'Indis' were irradiated with gamma rays at dosages of 15, 20, and 25 Gy. The irradiated spikes were pollinated with 'Inia 66' pollen and the F2 and F3 generations screened for translocation mutants, using the genes for leaf rust resistance and yellow endosperm pigmentation as markers. Finally, endopeptidase polymorphisms were utilized to select mutant translocation homozygotes within each of 29 families. An investigation of polymorphisms at the alpha-Amy-D2 and Wsp-D1 loci of chromosome arm 7DL revealed that 'Indis' did not produce an alpha-AMY-D2 product, but it did produce a novel WSP-D1 protein. The mutants were characterized for their leaf and stem rust resistances and the presence of WSP-D1 and yellow flour pigments. The stem rust resistance gene could not be accurately mapped. The linear order of the remaining loci on 7DL was centromere - leaf rust resistance - Wsp-D1 and yellow pigment. The data obtained suggested that the 'Indis' translocation has homo(eo)logy to the Lr19 translocation and homoeology to 7DL of common wheat. PMID- 1618388 TI - Nucleolar fragmentation in polytene trichogen cells of Lucilla cuprina and Chrysomya bezziana (Diptera: Calliphoridae). AB - The location of genes coding for 18S and 28S ribosomal RNA in mitotic and polytene cells of Lucilia cuprina and Chrysomya bezziana was investigated using in situ hybridization of an 18 + 28S ribosomal gene probe and silver staining. In both species ribosomal genes were localized to secondary constriction regions in sex chromosome heterochromatin. In L. cuprina mitotic cells the probe hybridizes to a distal secondary constriction region in the short arms of the X and Y chromosomes. In C. bezziana mitotic chromosomes ribosomal genes were located in distal secondary constriction regions in the long arms of the X and Y chromosomes. In polytene trichogen cells of both species, hybridization results varied with the level of polyteny. Cells of low polyteny have a single hybridization site, but with greater polytenization, increasing numbers of extrachromosomal fragments strongly hybridize to the ribosomal gene probe. No hybridization occurs in structures representing the sex chromosomes or in the autosomes. These results indicate that fragmentation and dispersal of the nucleolus occurs during polytenization. Silver staining of both unsquashed and squashed polytene nuclei show identical behaviour of multiple, varied-sized nucleolar bodies, thus confirming the in situ hybridization results. Uridine incorporation studies in L. cuprina indicated that transcription occurs in extrachromosomal bodies similar to nucleolar fragments. Nucleolar fragmentation is more pronounced in L. cuprina males, particularly in those with the translocation T(Y;2)540. Chromosomally normal C. bezziana show nucleolar fragmentation levels similar to that in L. cuprina males. Ribosomal genes are disproportionately replicated in trichogen cells to a much greater extent than surrounding heterochromatin. Nucleolar fragmentation may be a gene amplification system, but it is not known to what degree, relative to diploid amounts, ribosomal genes replicate in trichogen cells. PMID- 1618389 TI - Polytene chromosomes of the Old World screwworm fly (Chrysomya bezziana) and its evolutionary relationships with Lucilia cuprina and Cochliomyia hominivorax (Diptera: Calliphoridae). AB - Standard polytene chromosome maps for the Old World screwsworm fly, Chrysomya bezziana, are presented. Good quality polytene chromosomes obtainable from pupal trichogen cells allow detailed analysis of autosomal euchromatin. The sex chromosomes are represented by irregular heterochromatic structures resembling those described previously in trichogen polytene chromosomes of the Australian sheep blowfly, Lucilia cuprina. A high degree of homology with the banding pattern of L. cuprina polytene chromosomes allowed direct recognition of approximately 60% of the L. cuprina complement in the C. bezziana maps. A further 13% may be homologous. The extensive homology observed is discussed in relation to the rate of chromosome rearrangement and conservation of karyotype elements in the evolution of Calliphorid flies. The observed conservation in polytene banding patterns should facilitate construction of phylogenies over a number of generic groups. PMID- 1618390 TI - Development of a selection index to improve market value of cultured Atlantic salmon (Salmo salar). AB - Genetic parameters were estimated on growth and development traits using analyses of variance and covariance of 42 full-sib families from a select line, 39 full sib families from a control line of the same strain, and 37 full-sib families from another unselected strain. The traits included percent 1+ smolts, percent sexually immature fish after 1 year in seawater (nongrilse), and fork length measured at intervals throughout the production cycle. The number of fish sampled per family was 30 of 300-1500 for all freshwater traits and 15-60, i.e., all individuals present, for all seawater traits. Heritability estimates of freshwater traits had a broad range (0.15-0.61), but estimates were lower for seawater traits (0.06-0.29). There was a general reduction in heritability estimates for traits measured at increasing ages both in freshwater and seawater. These reductions may in part represent declines of maternal and common environmental effects that inflate heritability estimated from full-sib families. The genetic correlations indicated positive associations between freshwater and seawater growth parameters. However, the correlations decreased with increasing intervals between measurements. A selection index was developed using the estimates of the genetic and phenotypic parameters for three economically important traits: percent 1 + smolts, percent nongrilse, and harvest length. The seawater traits, percent nongrilse, and fork length at 17 months (harvest length) were the most important in the index. PMID- 1618391 TI - The polytene chromosomes of Drosophila triauraria and D. quadraria, sibling species of D. auraria. AB - The polytene chromosomes of Drosophila triauraria and D. quadraria, two of the sibling species of D. auraria, were examined. The polytene chromosomes of all three species exhibit very clear homology. Unlike the stock of D. auraria that we studied, D. triauraria and D. quadraria carry heterozygous paracentric inversions. In both species, 2R and 3R are the arms where these inversions are concentrated. In addition, in D. quadraria, the 3L chromosome arm is very complicated because of heterozygous inversions. The mode of inheritance of these rearrangements was studied. A homozygous strain for all chromosome arms of D. triauraria was isolated, while a homozygous strain was obtained only for the arms X, 2L, 3L, and 4 of D. quadraria. Like D. auraria, both species show a large number of inverted tandem duplications in the paired condition, even in the chromosomes of their hybrids. Small deletions were also detected, one of which, in D. triauraria, is homozygous terminal. Hypotheses are discussed concerning the relationships of the species and the existence of inverted tandem duplications. PMID- 1618392 TI - A polytene chromosome study of four populations of Anopheles aquasalis from Venezuela. AB - Polytene chromosome studies were undertaken to elucidate taxonomic relationships among populations of Anopheles aquasalis and A. emilianus in Venezuela. Four collection sites were chosen: two in Sucre state (Santa Fe and Guayana) where A. aquasalis (considered to be A. emilianus by Gabaldon and Escalante) is presumed to be the major regional vector of Plasmodium vivax; and two in areas where no malaria transmission occurs (Cano Rico, Aragua state, and Puerto Cabello, Carabobo state). The chromosome banding pattern of the four populations was identical and conformed to the standard chromosome map of A. aquasalis from Brazil. These results suggest that the population from Santa Fe and Guayana, considered to be A. emilianus, is conspecific with A. aquasalis. However, its status as a distinct species with a homosequential polytene chromosome banding pattern cannot be ruled out. PMID- 1618393 TI - Structure of the 5S rRNA genes in birch (Betula papyrifera) and alder (Alnus incana). AB - Hybridization of a 5S rDNA probe to Southern transfers of birch (Betula papyrifera) or alder (Alnus incana) DNA digested with BamH1 reveals similar triple-band "ladder-like" patterns. The sizes of sequenced 5S repeat units from both plants ranges only from 471 to 490 base pairs, suggesting that the complexity detected by Southern analysis is not due to different size classes of 5S repeats as found in other species. Within the intercistronic spacer region, conservation of large blocks of sequence between birch and alder 5S is observed implying a close evolutionary relationship between these two species. In both species, a duplication of part of the coding sequence including a restriction site for BamH1 introduces a second BamH1 site into the repeat unit. Differential methylation of the two BamHI restriction sites can account for the observed triple-band pattern. PMID- 1618394 TI - Studies of a spontaneous lethal mutation at the albino locus in SELH/Bc mice. AB - We report a new mutation at the albino locus in SELH/Bc mice. The mutation arose spontaneously in a male mouse that appeared to be a somatic and germ line mosaic for a new albino (c) allele, provisionally named cBc. The mutation is a recessive lethal, causing embryonic death soon after implantation. We have shown that there is no detectable activity of the Mod-2 allele in cis with the mutation and conclude that the mutation is probably a deletion that includes the c locus, the Mod-2 locus, the intervening 2 cM, and at least one locus essential for postimplantation embryonic survival, either proximal to the c locus or distal to the Mod-2 locus. This new mutation is similar to most previously reported spontaneous mutations at the albino locus in that it arose in a somatic and germ line mosaic mutant animal but differs from them in that it is an embryonic lethal when homozygous and is apparently a deletion. SELH/Bc mice appear to have a high mutation rate. This lethal albino mutation that appears to be a postmeiotic deletion should be useful in the search for the mechanism of mutagenesis in SELH/Bc mice. It may also be useful in mapping essential genes in the c-locus region. PMID- 1618396 TI - Nurses' aides: low pay, high turnover. PMID- 1618395 TI - Relationships between amino acid sequences determined through optimum alignments, clustering, and specific distance patterns: application to a group of scorpion toxins. AB - Optimum alignment in all pairwise combinations among a group of amino acid sequences generated a distance matrix. These distances were clustered to evaluate relationships among the sequences. The degree of relationship among sequences was also evaluated by calculating specific distances from the distance matrix and examining correlations between patterns of specific distances for pairs of sequences. The sequences examined were a group of 20 amino acid sequences of scorpion toxins originally published and analyzed by M.J. Dufton and H. Rochat in 1984. Alignment gap penalties were constant for all 190 pairwise sequence alignments and were chosen after assessing the impact of changing penalties on resultant distances. The total distances generated by the 190 pairwise sequence alignments were clustered using complete (farthest neighbour) linkage. The square, symmetrical input distance matrix is analogous to diallel cross data where reciprocal and parental values are absent. Diallel analysis methods provided analogues for the distance matrix to genetical specific combining abilities, namely specific distances between all sequence pairs that are independent of the average distances shown by individual sequences. Correlation of specific distance patterns, with transformation to modified z values and a stringent probability level, were used to delineate subgroups of related sequences. These were compared with complete linkage clustering results. Excellent agreement between the two approaches was found. Three originally outlying sequences were placed within the four new subgroups. PMID- 1618398 TI - Aging and mental health: prevention of caregiver overload, abuse, and neglect. Part 3. AB - This final installment of a three-part panel discussion on aging and mental health reviews the role of the primary care physician in issues of caregiver burden, elder abuse, and nursing home placement. Federal regulations and reimbursement policies have some effect on how the physician manages these concerns. A teamwork approach to geriatric case management that includes other health professionals is also discussed. PMID- 1618397 TI - Preventive geriatrics: basic principles for primary care physicians. AB - The goal of preventive geriatrics is to nurture a state of health that allows maximal active life expectancy while maintaining high levels of function. The physician's role in promoting such a state of health is disease prevention and the control of chronic diseases of aging. Barriers such as insufficient time and/or staff resources and insufficient third-party reimbursement restrict the delivery of multiple risk factor intervention and healthy aging counseling in the office setting. A systematic approach to preventive geriatrics proposed by the U.S. Prevention Services Task Force is discussed. PMID- 1618399 TI - Oral antibiotics: practical prescribing rules for practitioners. AB - Oral antibiotics are frequently prescribed for older patients for the treatment of such common bacterial infections as upper respiratory and urinary tract infections. Six practical prescribing rules can help control the cost of therapy. 1) Oral antimicrobials used to prevent hospitalization are always cost-effective. 2) Oral antimicrobials are always less expensive than parenteral antimicrobials. 3) Generic antimicrobials are not always less expensive than proprietary antimicrobials. 4) The best drug for the infection is usually the most cost effective in the long run, regardless of cost. 5) The use of antimicrobials for marginal indications is almost always cost-ineffective. 6) The simplest regimens are often the most cost-effective. PMID- 1618400 TI - Fetal tissue implants: therapy for Parkinson's disease?. Interview by Kevin Tanzillo. PMID- 1618401 TI - [Ludwik Fleck (1896-1961), bacteriologist and scientific theorist: science grows with collective thinking]. AB - This is a short biography of the Polish-Ukrainian-Israelian bacteriologist and science theoretician Ludwik Fleck, whose life was marked by wars, years of captivity in concentration camps and changes of nationality. His most important insight into the way in which scientific knowledge is gained was that knowledge is not the result of an individual process of a theoretical consciousness by itself, but the result of collective social activity. PMID- 1618403 TI - [S. A. Tissot and his effect on the "Dessau-Worlitzer Cultural Circle"]. AB - In the 2nd half of the 18th century, the small Duchy of Anhalt-Dessau was the model of an enlightened State, also in matters of health policy. The author stresses the influence of the Swiss Samuel-Andre Tissot on both Prince Leopold Friedrich Franz (1740-1817) and his foremost physician, Samuel Friedrich Kretzschmar (1730-1793). Tissot's influence manifested itself also in the early introduction of variolation. PMID- 1618402 TI - [The bacteriological revolution and theories of the etiology of goiter and cretinism]. AB - During the 19th century, a large number of researchers produced many different and even contradictory theories about the aetiology of endemic goiter and cretinism. The bacteriological revolution, i.e. the acceptance of the germ theory of infectious diseases, pushed scientists to try to isolate a germ for every disease. In the case of goiter and cretinism, this was fruitless endeavour. Nevertheless, the impact of the bacteriological revolution was largely positive because it provided a new scientific model of the genesis of disease and strengthened confidence in the possibility of fighting endemic as well as epidemic disease by simple but generally applied preventive measures such as, in the present case, iodine prophylaxis. PMID- 1618404 TI - [Aortic stenosis and pregnancy: presentation and physiopathology of a case]. AB - This is the case of a female patient, 31 years of age with the diagnosis of aortic stenosis, prolapse of mitral valve, aortic insufficiency, with pregnancy. The literature is reviewed and the management of this type of condition is analyzed. PMID- 1618405 TI - [Corpus luteum defect. Analysis of 30 cases in clinical pregnancy]. AB - Deficient corpus luteum (DCL) is an ovulatory dysfunction little defined but real. It is said that is frequency is 3 and 10% of sterile couples and 30 to 40% of habitual abortion. Is part of the group of ovulatory aberrations together with in situ luteinization and syndrome of not broken luteinized folicle. The diagnosis is based in endometrial morphology and progesterone determination. The objective of this work is to analyze 30 cases of DCL that achieved pregnancy. The diagnosis was done based on low determination of progesterone in serum, biopsy of irregular or indysphase endometrium and all the factors, remaining normal of esterility. Average age of patients was 36 years and for sterility 3.1. Treatment consisted in clomiphen cytrate (CC) administration 100 mg daily of hCG in 21 cases, CC only in eight cases and associated to bromocriptine in one case (concomitant hyper-prolactinemia); 26 pregnancies went to term, seven of them with support of exogenous progesterone the first weeks. There were three abortions and an ectopic one. It is concluded that with a complete study of sterility that only shows low seric progesterone and/or endometrium in dysphase or irregular, the diagnosis of DCL is probable and should be treated first with CC plus hCG. The evolution of pregnancies is normal and according to these results is little acceptable the use of progesterone as a support in pregnancy. PMID- 1618406 TI - [Rubella and pregnancy. Perinatal results]. AB - Twenty six patients at different stages of pregnancy and diagnosis of rubella were studied prospectively in order to evaluate the perinatal outcome. Diagnosis was based in the detection of specific IgM or on a four-fold rise in antibody titre (IHA) with an interval of three weeks between one and other specimen blood. The stage of pregnancy was defined as the interval between the last menstrual period and onset of the rash. The pregnancies surveillance was performed with biophysics test periodically. The pregnancies were terminated in base of the obstetrical conditions. The analyzed variables were: Maternal age, stage of pregnancy at the attack, duration of the rash, parity, clinical diagnosis of the newborn. Pregnancy continued in 16 patients and were followed up to the birth of the infants. The frequency of congenital infection after maternal rubella was more than 80% during the 4-8 weeks. Congenital rubella syndrome occurred in 2 newborn infected at the organogenesis period (4-8 weeks). Nevertheless there are 12 children identified serologically which do it interesting the following of these infants for to identify in an opportune form possible structural alterations as late manifestations of rubella. PMID- 1618407 TI - [GnRH-agonists in gynecology I]. AB - The present review has the objective to describe the chemical and pharmacological characteristics of GnRH analogs and the present time indications of it's use in gynecology. It is a critical review about use of GnRH analogs in: Anticonception, Assisted Reproduction, Uterine leiomyomas, Endometriosis, Polycystic Ovarian Syndrome, Precosious Puberty, Premenstrual Tension Syndrome and Breast Cancer. PMID- 1618408 TI - [Ovarian pregnancy. Presentation of a case and review of the literature]. AB - Ovarian pregnancy is a rare phenomenon with an incidence of 1 case in 7000 deliveries. We present a case implanted in the corpus luteum and discuss the possible etiology and the classification. We also review the diagnostic problems that it presents, and the advances made with transvaginal ultrasonography and hCG determinations in urine. The surgical management is presented, with special interest in conservative procedures. PMID- 1618409 TI - [Reliability of the pre-labor weight as a reference mark]. AB - Total weight gain during pregnancy has been an anthropometric mean associated with the birth condition. Based on the fact that it is impossible to evaluate every woman in the pregestational period, the referred pregestational weight at week 30 has been evaluated. Such validation was done, comparing the weight gain of a group of women that referred their pregestational weight, with another group who had both weights evaluated. The results suggest, that the women studied, knew and referred correctly the data. PMID- 1618411 TI - [Menopause, a critical stage in life]. AB - Menopause is the physiologic state that is consequence of ovarian function cessation and everyday more women reach it. In this article is reviewed the pathophysiology of menopause and treatment of osteoporosis. PMID- 1618410 TI - [Gynecologic and obstetric infections caused by aerobic bacteria]. AB - The anaerobic bacteria (AB) are between the most numerous microorganisms (mo) that constitute the flora of the female genital tract, so they can participate in the etiology of obstetric and gynecologic infections (OGI). The objective of this study was to investigate the frequency of AB isolations and the clinical characteristics of the anaerobic infections (AI) in patients of the National Institute of Perinatology, from January 1st, 1988 to May 31, 1991. AB were isolated from 117 patients who developed 163 infections; 167 anaerobic and 83 aerobic bacteria were recovered from these infections. The 99.2% were obstetric patients. The 85.5% of the isolations of AB were done from patients with endometritis, and 8.5% from postsurgical wound abscesses. Most of the AI were polymicrobial with a mean of 2.1 mo by infection. Peptostreptococcus, Clostridium and Bacteroids were the AB most frequent recovered. The majority of the patients had resolution of the infection within the first 5 days of antimicrobial treatment. There was no mortality in this group. We concluded that the AB have an important role in the etiology of OGI, then it is necessary that the treatment of these infections include antibiotics that cover AB. PMID- 1618412 TI - [GnRH-agonists in gynecology II]. AB - The present review has the objective to describe the chemical and pharmacological characteristics of GnRH analogs and the present time indications of it's use in gynecology. It is a critical review about use of GnRH analogs in: Anticonception, Assisted reproduction, Uterine leiomyomas, Endometriosis, Polycystic ovarian syndrome, Precocious puberty, Premenstrual tension syndrome and breast cancer. PMID- 1618413 TI - [Ovulation induction with gonadotropins aided by cervix mucus analysis and echography]. AB - Induction of ovulation was performed in 148 cycles using human menopausal gonadotropins (HMG) in 52 patients, seven with hypothalamic-pituitary failure and 45 suffering dysfunction at this level. Several induction schemes were used beginning on the second day of the cycle, until one or more follicles larger than 14 mm were found, to administrate 10,000 UI of human chorionic gonadotropin (HCG). Clinical valuation of cervical mucus and ultrasound of the ovaries to assess follicular development were done, from day eight of the cycle. Twenty five pregnancies resulted in 23 patients (44%), three in patients with failure and 22 in the dysfunction group. A total of 19 healthy babies were taken home, however three neonatal deaths, four miscarriages and one ectopic pregnancy occurred. Multiple gestation was present in three patients (12%), one was quadruplet, one triplet and one twin. The ovarian hyperstimulation syndrome (OHS) was detected in seven patients (13.4%), three were mild, two moderate and two severe; two cases of OHS had multiple pregnancies. Although induction of ovulation with HMG in patients with anovulation is a complex procedure requiring strict clinical vigilance and advanced technological resources, in this clinical study it was possible to obtain similar results to other series, using high resolution ultrasound only, without daily measurements of hormones. PMID- 1618414 TI - [2nd International Symposium of Gynecologic Surgery and Prevention of Adhesions. Palm Beach, Florida, January 31-February 2, 1992]. PMID- 1618415 TI - [Contralateral finger transplantation for reconstruction of thumb function]. AB - Finger transplantation from the contralateral hand for the purpose of thumb reconstruction is rarely performed, more widespread use of this procedure being prevented by the psychological problems for the patients. Two cases are described, in which a previously damaged index finger of the contralateral hand was transplanted. The metacarpophalangeal joint of the index finger replaced that of the thumb in both cases. A strong pinch grip with sensibility was achieved. The aesthetic result was substantially improved, both on the donor and the recipient hand. PMID- 1618416 TI - [Thumb reconstruction with cryopreserved autogenous thumb skeleton and microneurovascular flap]. AB - This paper describes a procedure for thumb reconstruction using autogenous cryo conserved bone from the thumb itself. In a case of severe explosion injury, the thumb and index finger were amputated at the carpometacarpal joint level and the remaining fingers at the distal interphalangeal joint level. Severe soft tissue damage and lesion of both the superficial and deep palmar arterial arches rendered customary surgical procedures for thumb reconstruction impossible. The cryo-conserved bone was replanted following soft tissue healing and then covered with a free radial forearm flap. This procedure resulted in a stable and painfree thumb and provided satisfactory grip. PMID- 1618417 TI - [Replacement of the long extensor tendon of the thumb by transposition of the index finger extensor tendon]. AB - Transposition of the extensor indicis seems to be the most common procedure for reconstruction of the ruptured or severed extensor pollicis longus (EPL) tendon. From 1959 to 1988, we performed 115 extensor indicis transpositions in 34 open EPL injuries and 81 subcutaneous EPL ruptures. The open injuries involved failed primary repair (n = 6) or untreated tendon injuries (n = 19). The subcutaneous ruptures occurred after distal radius fractures or other closed injuries of the wrist (n = 62), arthrosis or rheumatoid synovialitis (n = 8). Forty-seven patients returned for follow-up examination six months to 18 years after operation. The evaluation included twelve parameters involving thumb, index finger and overall hand function as well as subjective patient assessment. We found significant loss of motion and strength only in two cases, where the tension of the transposed tendon was obviously inadequate. A certain loss of independent index extension was without functional impairment. Although several authors prefer EPL reconstruction with an intercalated tendon graft, we recommend the extensor indicis transposition as a simple procedure with predictable satisfactory results. PMID- 1618418 TI - [Complications after surgical management of scaphoid pseudarthroses]. AB - The Matti-Russe technique yields a 95% success rate in treating scaphoid non unions diagnosed in the first years after trauma and without osteoarthrosis of the radiocarpal joint. Between October 1981 and December 1989, 215 patients were treated by Matti-Russe procedure at the University Hospital of "Bergmannsheil" Bochum. In ten cases, this operation did not lead to osseous consolidation. The results are presented and discussed. PMID- 1618419 TI - [Computerized tomography of the hand with high resolution technique]. AB - The results of 175 high-resolution computed tomography (CT) scans of the hand and wrist are analysed and compared to the results of conventional radiographs. Advantages of the procedure can be demonstrated when assessing pathological changes within the complex three-dimensional structure of the hand and wrist, and in the analysis of articular surfaces. In some cases, fractures and dislocations of the distal radioulnar joint and the carpal bones were missed in conventional radiographs. In cases of scaphoid fracture and nonunion, CT scans give valuable additional information surpassing the possibilities of conventional radiographs. For instance, bone healing after bone grafting can be better evaluated with a CT scan. Furthermore, preoperative planning is simplified, when tumors and cysts of the carpal bones can be located precisely using computed tomography. PMID- 1618420 TI - [Malposition of healed distal radius fracture. Indications, technique and timing of correction]. AB - Typical complications of distal radius fractures include post-traumatic malalignment in about 20%. This is associated with ulno-carpal pain and impaired wrist function. Various corrective procedures have been recommended. Between 1972 and 1986, 96 patients with posttraumatic disorders after distal radius fractures underwent surgical treatment. Three different procedures were carried out: simple corrective osteotomy of the distal radius, combined correction of the radius and ulna, as well as isolated correction of the ulna (distal resection, step-cut osteotomy, hemiresection arthroplasty). 83 (86.5%) of the patients were followed up for an average of 7 years postoperatively. The functional results were evaluated according to Lidstrom. Excellent and good results were found in 58 (69.9%), fair in 20 (24.1%) and bad results in 5 (6.0%). The best results were mostly seen in cases with a short interval between trauma and corrective procedure. Distal ulna resection has not been performed in our department since 1986 because of poor results and concommitant wrist-instability. We recommend combined correction procedures in those patients with painful deformities within a period of no more than six to nine months after trauma. The indication should also take individual aspects such as profession, age, activities, complaints, and radiological findings into account. Signs of osteoarthrosis and wrist disorders due to severe soft tissue problems are contra-indications to any of the aforementioned correction procedures. PMID- 1618421 TI - [Differential, oncologically adequate therapy of basalioma]. AB - Surgical treatment of basal cell carcinoma demands straightforward tumor management. This study investigated the radicality of surgical excision, procedures performed for defect coverage, the recurrency rate depending on the histological tumor type, among other parameters. Despite a low general incidence of 14%, sclerodermiformal BCC (morphea-like lesions) is found in 88% of all recurrencies. Based upon the results of this study, the following therapeutic guidelines are recommended: Resection with tumor-free margins must be insisted on, particularly in any exposed surfaces of the body. Histological subtyping by the pathologist is required. After initially incomplete resection in certain histological subtypes, subsequent radical resection is not mandatory. Complete resection of sclerodermiformal BCC is mandatory, and continuous follow-up of these cases is recommended. PMID- 1618422 TI - [Ultrastructure of the long flexor and extensor tendons of the hand in rheumatic tenosynovitis]. AB - Tendon ruptures are a frequent problem in patients affected by rheumatoid arthritis. The aim of the present study was to further characterize the known macroscopic changes of tendon tissue by micromorphological methods. Flexor and extensor tendon samples (n = 28) in rheumatoid arthritis were investigated by light- and transmission electron microscopy. In all cases, marked alterations in fibril architecture and structure were found. The fibril diameter showed a higher variability (range = 20-490 nm, x = 98.9 nm, s = 49.1 nm) in comparison with the control group of normal tendons (range = 20-290 nm, x = 119.0 nm, s = 34.9 nm). The average distance between the major bands in rheumatoid arthritis was reduced (from 57.3 nm down to 54.8 nm). Rare minor bands were detected. Oxytalan and mature elastic fibres were destroyed. These findings suggest that a causal correlation exists between altered matrix substructure and insufficient function of the tendon tissue in rheumatoid arthritis. PMID- 1618423 TI - [Posterior interosseous nerve paralysis after overexertion. A case report]. AB - Entrapment neuropathies in the upper extremity are common. Spontaneous paralysis of the posterior intersosseous nerve may occur by compression at the arcade of Frohse, where the nerve enters the plane between the superficial and deep muscle bellies of the supinator. Benign soft tissue tumors, minor trauma, and local inflammation have led to paralysis of the posterior interosseous nerve in several cases. An additional report on paralysis of this nerve a few days after overexertion with later spontaneous recovery is presented. PMID- 1618424 TI - Medical social work long-term care referrals for people with HIV infection. AB - Hospital social workers were surveyed to identify referral efforts and outcomes for clients with human immunodeficiency virus (HIV) infection who required long term placement. Over a three-month period, none of the 42 identified clients was admitted to a nursing home. In two-thirds of the cases, social workers contacted only one facility, and in about one-sixth of the cases, workers reported no placement attempts. Clients remained in the hospital a median overstay of eight days beyond acute care needs, representing 205 aggregate days that could have been spent in less intensive settings. Workers made few placement attempts because of beliefs that they would be unsuccessful or that nursing homes would not accept admissions. Increased communication and education both for referring workers and for long-term care facilities may improve the referral process, reduce costs, and decrease emotional distress for people infected with HIV. PMID- 1618425 TI - Social workers' knowledge about AIDS: working with vulnerable and oppressed people. AB - This study assessed social workers' differential knowledge about human immunodeficiency virus (HIV) infection. A questionnaire was mailed to a random sample of 500 members of the National Association of Social Workers in July 1988. Results show that social workers have the most information regarding transmission of HIV infection and the least information about the effects of HIV on specific subpopulations. Of particular concern was that respondents who stated they had either a personal or professional reason for being knowledgeable about acquired immune deficiency syndrome were no more informed about minority issues than those who did not think they had a personal or professional reason for being knowledgeable. PMID- 1618426 TI - Brown versus New York: the Rashomon of delivering mental health services in the 1990s. AB - This article examines a case study of one homeless mentally ill woman in New York City to show the differing perspectives on mental illness among mental health consumers, family members, mental health professionals, and advocates. Different issues emerge, and different priorities for care become clear. The social worker as case manager must design intervention strategies based on these differing perspectives, a crucial challenge for the profession. This article reviews the current literature on case management and suggests a holistic approach that better meets the needs of mentally ill people, their family members, and the community. PMID- 1618427 TI - Is case management effective for people with serious mental illness? A research review. AB - Recent literature on caring for people with serious mental illnesses reflects a growing belief in the effectiveness of case management services for this population. This article reviews recent outcome studies on case management to assess the extent to which prevailing claims that it is effective are supported empirically. Based on this review, the author concludes that the hypothesis that case management is effective remains plausible, but conclusive claims that its efficacy has been empirically demonstrated are premature. The outcome studies reflect diversity and ambiguity in the ways case management is conceptualized and implemented, problems in the research methodologies employed, and inconsistencies in outcomes. Consequently, implications for further research are drawn. PMID- 1618428 TI - I am John. AB - "John's" story details the history of services provided to people with mental retardation in the United States from the 1720s to the present. Although "John" is fictitious, the facts relating to mental retardation, service, and treatment through the years are accurate. There are no social workers in John's life story mainly because mental retardation has not been a part of schools of social work curriculum. John's life might have been different if there had been social workers advocating for him. PMID- 1618429 TI - Social work in health care regulation and legislation. PMID- 1618430 TI - Family as a resource: maintaining chronically mentally ill members in the community. PMID- 1618431 TI - Disability policy and social work practice. PMID- 1618432 TI - 'Concealed ovulation' and sexual signals in primates. AB - The absence of conspicuous sexual signals in some primates, particularly humans and vervets, has been interpreted as evidence that females of these species are 'concealing' ovulation from males. This conclusion is unjustified: the null hypothesis of no adaptation, that the absence of conspicuous sexual signals has resulted from the absence of selective pressures maintaining such adaptations, is both more parsimonious and better fits the facts. The related suggestion that there has been adaptation among females to conceal ovulation from their own consciousness is also unjustified. What, then, maintains sexual signals in those species that do have them? Many proposed hypotheses for the function of sexual signals do not account for their most puzzling feature: their conspicuousness. According to current theory on the evolution of communication, two explanations seem most plausible: conspicuous sexual signals function to communicate to distant receivers and/or to convince reluctant receivers. There is some empirical support for both hypotheses, but not overwhelming support for either. PMID- 1618433 TI - Oldest known Nannopithex (Primates, Omomyiformes) from the early Eocene of France. AB - Numerous dental remains of Nannopithex zuccolae, n. sp., from the terminal early Eocene locality of Premontre (Aisne), France, show the lower anterior dentition to be similar to that of other Nannopithex. Similarities include enlarged I1, reduced I2, reduced lower canine, loss of P2, small P3 and large P4. Upper molars, P3 and P4 all present primitive characters, making this species the most primitive as well as the oldest known microchoerid. PMID- 1618434 TI - Responses to a live snake by Lemur macaco macaco and Lemur fulvus mayottensis in captivity. PMID- 1618435 TI - Is there sex-biased mortality in primates? PMID- 1618436 TI - Sex-biased juvenile mortality in primates: a reply to Hauser and Harcourt. PMID- 1618437 TI - Allometry of food intake in free-ranging anthropoid primates. PMID- 1618438 TI - Basal metabolic rate, body weight and diet in primates: an evaluation of the evidence. AB - The relationship between basal metabolic rate (BMR), body weight and diet is examined for primates. Contrary to the results reported in several recent works, there is no strong evidence that diet is directly linked to BMR, although a low BMR, relative to body weight, may be found in species with folivorous diets. There is some evidence that nocturnal haplorhine species have a relatively low BMR, but strepsirhines appear to have a uniformly low relative BMR regardless of their primary activity period. The evolution of BMR in primates is discussed in the light of these findings. Some predictions are made about the relative BMRs that should be found for other species whose BMR is, as yet, unknown. PMID- 1618439 TI - Some features of Balkan endemic nephropathy. AB - This paper presents a brief review of the initial investigative efforts in three countries--"Yugoslavia", Bulgaria and Romania--on Balkan endemic nephropathy. There is now expert agreement that the disease represents an unusual type of chronic interstitial nephropathy of unknown aetiology. The epidemiological and histopathological data are summarized very briefly. The clinical symptoms and signs and the diagnostic approach to the disease are presented in greater detail. The possibilities of an early diagnosis in the latent, subclinical and early phases of the disease are discussed, together with the importance of the detection of a tubular type of proteinuria and enzymuria as a diagnostic aid. PMID- 1618440 TI - Epidemiology of Balkan endemic nephropathy. AB - The first outbreak of Balkan endemic nephropathy (BEN) was reported between 1955 and 1957, initially in Serbia and soon afterwards in Croatia and in Bosnia and Herzegovina. The disease appears to be of a focal nature. In Yugoslavia at least six foci are known, generally along major rivers of the Danubian river basin, in areas that have often been flooded in the past and even today suffer from high ground waters. The prevalence rate of the disease is reported to be between 2 and 10%. In the endemic area of Croatia, a systematic survey of 'in-the-field' cases of the disease since 1975 has shown a prevalence between 0.5 and 4.4%. When suspected cases are also included the prevalence rises to 20% or more. Specific mortality (based on official statistics) during the period 1957-1984 averaged 1.54/1000 per annum, but some studies have shown that mortality is actually more than twice as high as this figure. More women are affected than men; women also more frequently die of BEN than men. Lethality is extremely high. A striking feature of BEN is the familial occurrence of the disease. Incidence does not seem to be connected with ethnic group differences. Immigrants into the endemic area may also contract the disease. An increased incidence of malignant tumours of the urinary tract has been recorded in populations living in endemic areas. Epidemiological characteristics suggest that the disease is contracted in the domestic situation, or possibly from other family members. Factors to be considered are food, water or long close contact. It is also possible that the disease is contracted outside the house, in connection with farming activities, since the affected persons are almost exclusively farmers. PMID- 1618441 TI - Clinical features of Balkan endemic nephropathy. AB - This paper describes the clinical symptoms and signs of Balkan endemic nephropathy (BEN). The initial asymptomatic period followed by weakness and lassitude during renal insufficiency is emphasized. Non-characteristic lumbar pain may be present and episodes of macrohaematuria may occur. There is no fever, no severe dysuria, and no general disease preceding the symptoms. No oedema of the nephrotic type is recognized. Working capacity is unaffected until the late stage of the disease. In the advanced stages pallor of the skin and xantochromia of palms and soles are noticeable. Blood pressure is normal, but in the advanced phase may be elevated. In the uraemic phase a full uraemic syndrome is found. Urothelial tumours are frequent, occurring in 2-47% of cases; tumour cells may be found in the urine. Proteinuria of tubular type may be found early; in the uraemic phase it is constant. In the urinary sediment there are scarce white and red blood cells (the latter episodically abundant). Bacteriuria is present in about 20% of women patients. Glucosuria (less than 10%) and aminoaciduria (less than 10%) have been reported. In the early stages of BEN the urine concentration capacity is impaired earlier than renal blood flow and glomerular filtration rate. Enzymuria is present in the early phases. Tamm-Horsfall protein may be increased in the urine. Normo- or hypochromic normocytic hyporegenerative anaemia is a frequent finding. Bone marrow and leucocytes are normal. Serum proteins and immunoglobulins are not altered. Complement is normal; anti-glomerular basal membrane and anti-tubular basal membrane are negative. On radiography, kidney size varies from normal to the size of a small contracted kidney. The clinical picture of the disease is that of a slowly progressing tubulo-interstitial chronic nephritis. PMID- 1618442 TI - Pathomorphology of Balkan endemic nephropathy. AB - Within the county of Slavonski Brod, Yugoslavia hyperendemic areas of Balkan endemic nephropathy (BEN) have been recognized for a long time. As the Department of Pathology and Forensic Medicine of the Medical Centre in Slavonski Brod is responsible for all diagnostic post-mortem examinations in the county, and at the same time is engaged in surgical pathological diagnosis, a considerable amount of material relating to BEN and concomitant urinary-tract tumours has been collected during a 16-year period. This material has been classified and used for pathological, anatomical and histological investigations. In this paper the most relevant findings are described and briefly discussed, without the intention to speculate on possible aetiology of BEN. As the origin of BEN and of the high frequency of urinary tumours among the people from the endemic areas are still unexplained, and uniform criteria for the pathomorphological diagnosis of BEN are badly needed, the proposal to set up an archive encompassing cases from all the centres investigating BEN is supported. PMID- 1618443 TI - Ochratoxin A in blood and its pharmacokinetic properties. AB - Since there are pathomorphological similarities between porcine mycotoxic nephropathy caused by ochratoxin A and Balkan endemic nephropathy (BEN), it has been suggested that the same aetiological agent has a role in BEN. Based on the results from several field and experimental studies carried out on pigs, an appropriate analytical method of monitoring possible human exposure to ochratoxin A was developed. The toxicokinetic properties of the toxin were species specific, although in all the animal species studied (with the exception of fish), as well as in humans, two binding proteins were found in the plasma. The monkey had the longest elimination half-life of the toxin, 510 hr, in contrast to the fish whose elimination half-life was only 0.68 hr. The fish kidney displayed a specific pattern of distribution. In the laying quail the most prominent observation was the accumulation of labelled ochratoxin A in egg yolk. Generally, [14C]ochratoxin A was eliminated rapidly from the quail body, but had a long retention time in the circulating blood in the mouse. Although the elimination of ochratoxin A from the body depending on its binding to plasma constituents, the existence of enterohepatic circulation might have been partially responsible for its prolonged retention and elimination from the body of mammals. The toxicokinetic profile of ochratoxin A did not contradict the mycotoxic hypothesis in the aetiology of BEN. PMID- 1618444 TI - Relevance of a rat model of papillary necrosis and upper urothelial carcinoma in understanding the role of ochratoxin A in Balkan endemic nephropathy and its associated carcinoma. AB - Ochratoxin A is nephrotoxic and has been implicated in the genesis of Balkan endemic nephropathy (BEN), a condition that leads to end-stage renal disease and upper urothelial tumours. This compound induces renal parenchymal carcinoma in male mice only, and is not considered to be a potent carcinogen nor is there experimental evidence of its propensity to cause upper urothelial carcinoma. There is, however, evidence that exposure to more than one mycotoxin may be an important factor in the clinical spectrum of BEN. Analgesic nephropathy is clinically different, but is also associated with an upper urothelial carcinoma. The combination of urothelial initiation and an acute papillary necrosis in rats produces upper urothelial carcinoma. This two-stage experimental model offers the potential to assess the role of ochratoxin A in BEN-associated upper urothelial carcinoma under experimental conditions. PMID- 1618445 TI - Role of ochratoxin in disease causation. AB - Under experimental conditions renal damage has been induced by alimentary exposure to ochratoxin A in all single-stomach animals tested so far, including rodents, dogs, pigs and birds, and even in young ruminants still functioning as single-stomach animals. Most information on ochratoxin-induced nephropathy has been obtained in pigs during experimental studies comprising structural as well as functional changes. The renal damage is characterized morphologically by atrophy of the proximal tubules, interstitial cortical fibrosis and sclerotized glomeruli, and functionally by impairment of tubular function indicated by a decrease in TmPAH/Cin and reduced ability to produce concentrated urine. The renal effect has been observed using exposure levels of ochratoxin A in the range 200 to 4000 micrograms/kg feed. Field cases of ochratoxin-induced nephropathy in pigs have been encountered in many countries, and the disease mycotoxic porcine nephropathy (MPN) is recognized as an endemic disease entity in several northern and central European countries. Epidemics of MPN have been reported, closely related to excessive climatic conditions in periods preceding harvest. Ochratoxin A is a recognized renal carcinogen in the mouse. In female pigs exposed to alimentary ochratoxin A for 2 years, no renal cancer was observed. Ochratoxin A is metabolized and excreted relatively fast in animals, with an RL50 (residue elimination) in the pig of a few days for various tissues. Past exposure data is a requirement in retrospective epidemiological studies, but because of the short RL50 values tissue analysis for ochratoxin A is unlikely to provide that kind of data, in animals or in humans. In order to meet this demand a procedure has been developed, using renal biopsy material for activity analysis of two renal tubular enzymes, phosphoenolpyruvate carboxykinase and gamma-glutamyl transpeptidase. In pigs exposed to ochratoxin A for 1 week a 40% reduction of the enzyme activity was observed. The dose-related activity decrease of the two enzymes was accompanied by a dose-related aggravation of renal impairment, as measured by a reduction of TmPAH/Cin, suggesting that these enzymes are sensitive indicators of ochratoxin A-induced nephropathy. PMID- 1618446 TI - Styrene migration from general-purpose and high-impact polystyrene into food simulating solvents. AB - General-purpose and high-impact polystyrenes (GPPS and HIPS, respectively) are used in many food-contact applications for the packaging of aqueous-based, fatty and dry foods. The correlation of residual styrene concentrations in polystyrene with styrene migration into food-stimulating solvents is of interest in order to predict the potential exposure of consumers to styrene from food-packaging applications. Studies of the migration of styrene into 8% ethanol and cooking oil from a GPPS and a HIPS polymer, each containing three different residual styrene levels, have been completed at temperatures ranging from 70 to 180 degrees F (21 to 82 degrees C). The results showed that the amount of styrene migrating from both polymers into cooking oil was proportional to the square root of the time of exposure, and the total amount of styrene migrating was proportional to the residual levels of styrene in the polymers. The calculated diffusion coefficients were found to be independent of the residual levels of styrene in a given polymer at a given temperature. While the partition equilibrium was not approached when the polymers were exposed to cooking oil, it was observed in the 8%-ethanol exposure studies. The calculated partition coefficients between the polymers and 8% ethanol appeared to be independent of the residual levels of styrene in the polymers at a given temperature. Linear relationships were observed between the logs of the diffusion and partition coefficients and the inverse of the absolute temperature of exposure. PMID- 1618448 TI - Sex difference in the nephrotoxicity of thiabendazole in mice depleted of glutathione by treatment with DL-buthionine sulphoximine. AB - In ICR mice depleted of glutathione (GSH) by treatment with DL-buthionine sulphoximine (BSO), males were much more susceptible to thiabendazole (TBZ) nephrotoxicity than females. The nephrotoxicity was indicated by increases in relative kidney weight and serum urea nitrogen (SUN) concentration and by a decrease in renal GSH concentration at 24 hr after TBZ administration. The susceptibility of males to TBZ-induced nephrotoxicity was completely eliminated by pretreatment with oestradiol (OD). Castration of male mice also reduced, though not completely, their susceptibility to TBZ nephrotoxicity. In females pretreated with testosterone (TS), the nephrotoxic effect of TBZ was increased to an extent comparable with that in males. PMID- 1618447 TI - Effects of selected secondary metabolites of Fusarium moniliforme on unscheduled synthesis of DNA by rat primary hepatocytes. AB - The Fusarium moniliforme mycotoxins--fusarin C, fumonisin B1, moniliformin and bikaverin--were evaluated for genotoxicity by their ability to induce unscheduled DNA synthesis (UDS) in primary rat hepatocytes. Isolated hepatocytes were exposed to several concentrations of moniliformin (5.0-500 microM), bikaverin (1.0-500 microM), fumonisin B1 (0.5-250 microM), or fusarin C (1.0-100 microM). Aflatoxin B1, a known inducer of UDS, was included as a positive control. UDS was determined by autoradiography of cells after their exposure to [3H]thymidine. The highest doses of fusarin C and bikaverin caused cell death, but no cytotoxicity was observed in cells exposed to moniliformin or fumonisin B1. Fumonisin B1, moniliformin and bikaverin were not genotoxic in the UDS assay. The results of the UDS assay with fusarin C were inconclusive since a marginal effect on UDS was obtained. PMID- 1618449 TI - Lack of renal tumour-initiating activity of a single dose of potassium bromate, a genotoxic renal carcinogen in male F344/NCr rats. AB - The renal tumour-initiating activity of potassium bromate (KBrO3), a known genotoxic rat renal carcinogen, was investigated in male F344/NCr rats. 6-wk-old rats were given KBrO3 intragastrically as a single dose of 300 mg/kg body weight, which was confirmed by our preliminary toxicity study as a maximum tolerated single dose for this strain of rat. Starting 2 wk after KBrO3 treatment, groups of 39 rats received either a basal diet or a diet containing 4000 ppm barbital sodium (BBNa) as a promoting regimen and were killed at 30, 52, or 104 wk. Control rats received either dietary BBNa (4000 ppm) or the basal diet alone from wk 2 to 52 or 104 wk. Nephropathy was observed in all rats treated with KBrO3 followed by BBNa at 30 wk and in rats receiving BBNa alone, but not in rats exposed to KBrO3 alone. Dysplastic renal tubular cell foci (DTF), putative preneoplastic renal tubular cell lesions were found associated with nephropathy in rats exposed to KBrO3 followed by BBNa from 47 wk. The incidences and multiplicities of DTF and renal tubular cell tumours observed from 31 to 104 wk revealed no initiating effect of KBrO3 treatment. These results indicate that the KBrO3 dose of 300 mg/kg did not initiate renal carcinogenesis. PMID- 1618450 TI - Sodium monochloroacetate poisoning of greenfinches. AB - A large number of passerine birds, mainly greenfinches, were found dead or dying in a hedgerow close to a field of onions recently sprayed with sodium monochloroacetate (SMCA). An analytical method is described for isolating monochloroacetic acid from bird tissues, as its potassium salt, by ion exchange chromatography. The ion exchange eluate is evaporated to dryness, acidified, extracted with ether and the ethereal extract methylated with diazomethane. The concentration of the methyl ester of monochloroacetic acid is determined using the Mass Selective Detector in the selected ion mode. Chemical analysis confirmed the exposure of the birds to SMCA. It is calculated that 50 microliter of spray contained the lethal dose of SMCA for a greenfinch. PMID- 1618451 TI - Semen fingerprint. PMID- 1618452 TI - Age estimation from the structure of adult human teeth: review of the literature. AB - The literature on age estimation from the structure of adult human teeth is reviewed. Several anatomic changes of teeth have been shown to be valuable in age determination, but there is still controversy concerning the accuracy of cemental annulation. It is believed that improvements in age estimation can be made using direct measurement rather than scoring systems. PMID- 1618453 TI - An express immunological method for detection of human seminal plasma. AB - Monoclonal antibodies (Mabs) against human seminal plasma (HSP) were produced and during screening procedures dissociation constants of the antigen/antibody complexes were determined. Mab 1E5 was selected for further studies because of its high reactivity in an enzyme-linked immunoassay (ELISA) and high affinity for its corresponding antigen. The specificity of Mab 1E5 was checked in absorption ELISA with human organ extracts and some biological secretions. It was established that the 1E5-corresponding epitope was a thermostable peptide moiety which could be detected in HSP, only. This monoclonal antibody was used for the development of an express method for detection of human semen. The assay was applied for screening of 57 cases of suspected rape. A complete correlation was found between the results obtained by the proposed test and by routine microscopic methods. The newly designed immunoassay is reliable, it is easily performed and it is less time-consuming. PMID- 1618454 TI - Rectal temperature time of death nomogram: dependence of corrective factors on the body weight under stronger thermic insulation conditions. AB - Ninety-eight test coolings were made under various cooling conditions (moving air, two types of both clothing and covering) on dummies of real masses of 1, 3.3, 9.9, 24.5 and 33.4 kg, respectively, which cool under standard conditions (unclothed, uncovered, still air) like human bodies of 14, 33, 41, 83 and 104 kg, respectively. The results provide evidence of a non-linear dependence of corrective factors of body weight upon the body weight. The dynamics of the dependence increases with the thickness of thermic insulation. Transferred to the use of the nomogram method on bodies, cooling conditions requiring corrective factors between 0.75 (moving air) and 1.3 (rather thin clothing/covering), known from experience on bodies of an average weight, can be used as in the past, independent of the body weight. According to experience the dependence of corrective factors on the body weight must be taken into account in bodies of a very high or low body weight. For that purpose both a simplified table and a formula for computing is given. PMID- 1618455 TI - Quantitative liquid chromatography, thermospray/tandem mass spectrometry (LC/TSP/MS/MS) analysis of some thermolabile benzodiazepines in whole-blood. AB - An LC/TSP/MS/MS selected reaction monitoring (SRM) method in the daughter ion scan mode can be applied successfully for the quantitative determination of thermolabile benzodiazepines in whole-blood following an Extrelut extraction method. Detection limits as low as 100 pg per injection can be reached for all benzodiazepines. The benzodiazepines under investigation proved to be stable, with the exception of ketazolam for which complete degradation to diazepam was observed. PMID- 1618457 TI - The occurrence of cervical fractures in victims of judicial hanging. AB - Cervical vertebrae from 34 victims of judicial hanging were examined. In only six cases was there a fracture of the axis and only one other fracture was seen in the series. The fractures were of two types. Three were the traditional 'Hangman's fracture' whilst three were of a type previously unreported. The incidence of fracture was unassociated with drop, date age or hangman. The results of the post mortems on these subjects were reviewed and found to be grossly inaccurate with regard to fractures. The results indicate that the traditional hangman's fracture occurred in only a small proportion of cases of judicial hanging. The cause of fractures and cause of death in judicial hanging are discussed with a brief history of judicial hanging in this country. PMID- 1618456 TI - Rapid death from thrombotic thrombocytopaenic purpura following caesarean section. AB - We report a case of rapid death from thrombotic thrombocytopaenic purpura (TTP) in a young pregnant lady who developed full blown symptoms soon after caesarean section. Extensive intramyocardial confluent haemorrhages and widespread microthrombi in heart, brain, adrenals and kidney were found at autopsy. Thrombotic thrombocytopaenic purpura is an uncommon condition, which carries a high fatality rate if untreated. Awareness of this syndrome together with its high risk of sudden death underlines the importance of rapid diagnosis and treatment. PMID- 1618459 TI - Patient transport--"hitching a ride". PMID- 1618458 TI - Screening and confirmation of drugs in urine: interference of hordenine with the immunoassays and thin layer chromatography methods. AB - Hordenine cross-reacted with various enzyme linked immunosorbent assay (ELISA) or radioimmunoassay (RIA) kits used for the screening of urine samples. Morphine ELISA kit was most sensitive, whereas etorphine- and buprenorphine-ELISA kits were least sensitive to hordenine cross-reactivity. Hordenine also interfered with the thin layer chromatography of oxymorphone, hydromorphone and apomorphine. The major source of hordenine in humans is beer brewed from barley, whereas the major source of hordenine in horses is canary grass or barley. Therefore, the presence of hordenine in the urine of humans consuming beer or in the urine of horses consuming canary grass may give false positive values when the immunoassay and TLC methods are used for the screening of the urine sample. In order to distinguish hordenine from the opiate drugs, simple and sensitive gas chromatographic/mass spectrometric (GC/MS) and high performance liquid chromatographic (HPLC) methods have been developed in this study. PMID- 1618460 TI - My experience as a courier. PMID- 1618461 TI - My experience as a courier. PMID- 1618462 TI - Patient transport--yesterday and today. PMID- 1618463 TI - Intracranial pressure monitoring and liver transplantation for fulminant hepatic failure. AB - Cerebral edema and intracranial hypertension, commonly present in fulminant hepatic failure, may lead to brainstem herniation and limit the survival of comatose patients awaiting liver transplantation before a donor organ becomes available. Also, they are likely responsible for postoperative neurological morbidity and mortality. Although intracranial pressure monitoring has been proposed to aid clinical decision making in this setting, its use in the prevention of brainstem herniation preoperatively, in the selection of patients for liver transplantation who have the potential for neurological recovery and in the maintenance of cerebral perfusion during liver transplantation has not been examined in detail. To address these issues, we established a protocol for intracranial pressure monitoring in comatose patients with fulminant hepatic failure as part of their preoperative and intraoperative management. Twenty adults and three children underwent intracranial pressure monitoring. Ten patients required preoperative medical therapy with mannitol, barbiturates or both for a rise in intracranial pressure above 25 mm Hg. Four patients had a sustained lowering of intracranial pressure, three of whom survived hospitalization. Six patients had intracranial hypertension refractory to medical management, were removed from a waiting list for a donor organ and died with brainstem herniation. Of the remaining 17 patients, 3 died of other causes while awaiting a donor organ, 2 recovered spontaneously without neurological sequelae and 12 underwent liver transplantation. All but one patient undergoing liver transplantation had transient intraoperative intracranial hypertension develop, requiring medical treatment. The 12 patients who had transplants recovered neurologically and were discharged from the hospital.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618464 TI - Direct measurement of hepatic blood flow in native and transplanted organs, with accompanying systemic hemodynamics. AB - The purpose of this study was to investigate intraoperatively a population of patients with end-stage liver disease before and after liver transplantation with respect to (a) the range of hepatic and systemic hemodynamics and their changes associated with transplantation and (b) the ability to identify native hemodynamic correlates with specific diagnostic groups. Hepatic artery and portal vein blood flows were determined with square-wave electromagnetic flowmetry. Significant differences related to the type of preservation solution used--Euro Collins or University of Wisconsin--were identified in some hepatic and systemic hemodynamic measurements from the graft livers. Specifically, cardiac output, total liver blood flow and liver weight were significantly increased in the Euro Collins group compared with the native and University of Wisconsin groups. Hepatic artery flow was significantly greater and portal vein pressure was significantly lower in the University of Wisconsin group than in the native or Euro-Collins group. In general, comparing the graft and native livers, hepatic artery and portal vein blood flow increased significantly after transplantation, as did hepatic oxygen consumption. Portal vein pressures were dramatically reduced, but systemic arterial pressure remained remarkably constant. The percentage of cardiac output going to the liver increased, as did the portal vein percentage of the total liver blood flow. Diagnostic groups could not clearly be associated with characteristic native liver or systemic hemodynamics. Hemodynamics may be associated more with the stage of the disease process than the disease itself. PMID- 1618465 TI - Sodium benzoate in the treatment of acute hepatic encephalopathy: a double-blind randomized trial. AB - A prospective randomized double-blind study was conducted to evaluate the efficacy of sodium benzoate in the treatment of acute portal-systemic encephalopathy. Seventy-four consecutive patients with cirrhosis or surgical portasystemic anastomosis and hepatic encephalopathy of less than 7 days duration were randomized to receive lactulose (dose adjusted for 2 or 3 semiformed stools/day) or sodium benzoate (5 gm twice daily). Assessment of response included mental status, asterixis, arterial ammonia level, electroencephalogram and number-connection test. Each was given a score between 0 and 4+. A portal systemic encephalopathy index was calculated with these scores. Visual, auditory and somatosensory evoked potentials and a battery of psychometric tests for intelligence and memory were also performed to assess improvement. Thirty-eight patients received sodium benzoate; 36 took lactulose. Thirty patients (80%) receiving sodium benzoate and 29 (81%) receiving lactulose recovered; the remaining patients died. Improvement in portal-systemic encephalopathy parameters occurred in both treatment groups and was similar (p greater than 0.1). Electroencephalogram and evoked potentials were not as helpful as mental status in assessing of recovery. Psychometric test scores remained abnormal after recovery of mental status (21 to 42 days) and were probably too sensitive for monitoring of these patients. The incidence of side effects was similar in the two treatment groups. The cost of lactulose for one course of therapy was 30 times that of sodium benzoate. We conclude that sodium benzoate is a safe and effective alternative to lactulose in the treatment of acute portasystemic encephalopathy. PMID- 1618466 TI - Association between heterozygous alpha 1-antitrypsin deficiency and genetic hemochromatosis. AB - Primary hemochromatosis is a genetically determined autosomal recessive disorder characterized by the excessive accumulation of body iron, most of which is deposited in the parenchymal cells of various organs. alpha 1-Antitrypsin deficiency is characterized among others by defective secretion of alpha 1 antitrypsin from liver cells. Whereas the risk of cirrhosis is increased in homozygous patients (PI ZZ) and possible in heterozygous patients (non-PI MM) as well, a greater risk for hepatocellular carcinoma has been suggested only in homozygous patients. Because these two metabolic disorders are relatively common, it has been difficult to determine whether they are associated with each other. In this study, we tried to determine the relationship between these two disorders using the case material seen at the University of Pittsburgh during a 7-yr period. We studied 15 patients with genetic hemochromatosis. alpha 1-Antitrypsin quantitation and phenotyping were performed in each case using standard methods. The distribution of the various Pi phenotypes was compared with that found in a normal population and reported elsewhere. Odds ratio and chi 2 tests were used to measure the relative risk and significance of association, respectively. Eleven patients (73%) were found to be PI M and four (27%) were identified as being heterozygotes: three (20%) were PI MZ, and one (7%) was PI MS. The prevalence of the PI MS phenotype was similar to that in the general population (7% vs. 6.4%; NS). The PI MZ phenotype, however, was statistically more common in patients with hemochromatosis than in the general population (20% vs. 2.2%; p less than 0.004).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618468 TI - Neurological complications after liver retransplantation. AB - Postoperative neurological complications in 185 patients who underwent two or more orthotopic liver transplantations were reviewed. The most common neurological complications were alteration of mental status (84%), seizures (33%) and focal motor deficits (15%). The frequency of neurological complications after a second orthotopic liver transplantation was significantly greater than that after a single orthotopic liver transplantation. However, neurological complications were more frequent after a second orthotopic liver transplantation than after a third transplant. Significantly more neurological complications occurred in patients who did not survive a year than in those who did, regardless of the number of transplants they underwent. These findings indicate that the risk of neurological complications among patients with multiple orthotopic liver transplantations is greater in those who require a second transplant; this risk appears to diminish after a third transplant. Importantly, the presence of neurological complications is associated with increased post-orthotopic liver transplantation mortality rate. PMID- 1618467 TI - Plasma levels of brain natriuretic peptide in patients with cirrhosis. AB - Plasma levels of brain natriuretic peptide, a recently identified cardiac hormone with natriuretic activity, were measured in 11 healthy subjects, 13 cirrhotic patients without ascites, 18 nonazotemic cirrhotic patients with ascites and 6 patients with cirrhosis, ascites and functional kidney failure. Plasma levels of brain natriuretic peptide were similar in healthy subjects and cirrhotic patients without ascites (5.56 +/- 0.65 and 7.66 +/- 0.68 fmol/ml, respectively). In contrast, cirrhotic patients with ascites, with and without functional kidney failure, had significantly higher plasma concentrations of brain natriuretic peptide (19.56 +/- 1.37 and 16.00 +/- 1.91 fmol/ml, respectively) than did healthy subjects and patients without ascites (p less than 0.01); no significant difference was found between the two groups of cirrhotic patients with ascites with respect to this parameter. In the whole group of cirrhotic patients included in the study, brain natriuretic peptide level was directly correlated with the degree of impairment of liver and kidney function, plasma renin activity and plasma levels of aldosterone and atrial natriuretic peptide. The results of this study indicate that brain natriuretic peptide is increased in cirrhotic patients with ascites and suggest that sodium retention in cirrhosis is not due to deficiency of this novel cardiac hormone. PMID- 1618469 TI - Hepatic fibrosis in rats produced by carbon tetrachloride and dimethylnitrosamine: observations suggesting immunoassays of serum for the 7S fragment of type IV collagen are a more sensitive index of liver damage than immunoassays for the NH2-terminal propeptide of type III procollagen. AB - Liver fibrosis was induced in rats both with carbon tetrachloride and dimethylnitrosamine. Assays were performed on steady-state levels of messenger RNAs in the liver for several collagens and basement membrane components. The results indicated marked increases in the steady-state levels of messenger RNA for type I collagen, type III collagen, type IV collagen and the B2 component of laminin. In the same animals, immunoassays were performed for serum levels of the N-terminal propeptide of type III procollagen and the 7S fragment of type IV collagen. The results demonstrated an increase in the serum levels of 7S fragment that occurred early and closely paralleled the increase in the steady-state levels of messenger RNA for the alpha 1(IV) chain of type IV collagen. In contrast, no significant increase was seen in the serum levels of the N propeptide of type III procollagen. The results suggest that immunoassays for 7S fragment of type IV collagen in serum are a more sensitive index for liver cell damage and fibrosis than assays for the N-propeptide of type III procollagen. The results suggest that greater attention should be paid to assays of 7S fragments in assessing hepatic fibrosis in man. PMID- 1618470 TI - Uptake of a protein-bound polar compound, acetaminophen sulfate, by perfused rat liver. AB - The hepatocytic entry of acetaminophen sulfate conjugate was examined in the rat liver, perfused with red cells with and without albumin, by use of the multiple indicator dilution technique. [3H]acetaminophen sulfate was injected into the portal vein in a bolus of blood containing 51Cr-labeled red blood cells (a vascular reference), sucrose (a low-molecular-weight interstitial reference) or 125I-labeled albumin (a high-molecular-weight interstitial reference, included when albumin was present), and the time courses of their outflow into the hepatic venous blood were observed. The [3H]acetaminophen sulfate, which binds partially to albumin, emerged between albumin and sucrose in the presence of albumin, processed the upslope of the sucrose curve and showed a late low-in-magnitude tailing; the precession disappeared in the absence of albumin. Biliary excretion of [3H]acetaminophen sulfate was less than 1% of the dose. Quantitative evaluation with a barrier-limited, space-distributed variable transit time model (including rapidly equilibrating albumin binding) accounted for the albumin effect on [3H]acetaminophen sulfate behavior and demonstrated a low liver cell permeability for the acetaminophen sulfate and a small interstitial binding space for its nonalbumin-bound fraction in excess of that for sucrose, which in the absence of albumin was of similar dimensions. PMID- 1618471 TI - Changes of IgG-bearing cell populations in the portal tracts of patients with chronic liver disease of viral etiology: an evaluation by immunoperoxidase method and computerized image analysis. AB - Little is known about the distribution of IgG-bearing cell subpopulations in normal liver and their possible changes in disease conditions. We developed an immunohistochemical method that proved suitable and accurate for the identification and characterization of IgG-bearing cells and their subpopulations in liver specimens. The method uses specific monoclonal antibodies on serial mirror liver sections. We applied this method to four normal liver tissue specimens and 25 liver biopsy samples of chronic hepatitis of viral etiology. Only rare IgG-bearing cells could be observed in the portal tracts of normal liver specimens. In contrast, a dense infiltrate of such cells was seen in liver specimens from patients with chronic viral hepatitis. The density of IgG-bearing cells in such patients ranged from 6 to 20 cells x 10(-4) micron2 in the different specimens (mean = 11 x 10(-4) micron2). The increase in IgG-bearing cells did not appear to be related to the histological diagnosis, to the degree of histological inflammatory activity or to the type of viral infection. The major population of IgG-bearing cells consisted of IgG1-positive cells (68%); IgG2- (17%), IgG3- (8%) and IgG4 (7%)-bearing cells represented only minor fractions. The increased prevalence of IgG1-bearing cells observed in chronic hepatitis but not in normal liver specimens suggests that these findings may reflect an activation of antibody production directed toward viral antigens or antigenic structures of self. The identification of the antigenic specificities of the antibodies produced by IgG-bearing cells might provide important clues in understanding the pathogenesis of chronic viral hepatitis. PMID- 1618473 TI - Ethinylestradiol increases volume and decreases sinusoidal membrane surface in the rat liver: a stereological analysis. AB - Structural alterations of liver parenchyma caused by ethinylestradiol, a synthetic estrogen known to induce cholestasis and to act as a tumor promoter factor, were investigated. Male rats treated with 17 alpha-ethinylestradiol (5 mg/kg body weight for 5 days) were compared with controls (n = 5 each). After perfusion fixation and systematic random sampling, paraffin sections, semithin sections and thin sections were examined observing standard stereological techniques. Ethinylestradiol treatment induced an increase in liver volume by 65% (p less than 0.001), which was caused more by hypertrophy (volume of singular hepatocyte +35%, p less than 0.001) than by hyperplasia (number of hepatocytes +23%, p less than 0.001). A decrease in sinusoidal membrane surface density ( 43%, p less than 0.005) associated with a decrease in sinusoidal microvillar volume density (-50%, p less than 0.005) were both compensated for by the increase in liver volume. No canalicular alterations were observed. Thus changes in hepatocytes detectable with stereological techniques affect the sinusoidal pole where decreased sinusoidal membrane surface is associated with or reflects a substantial loss of membrane phospholipids. The increased liver volume may constitute an adaptive response compensating for the relative decrease in sinusoidal membrane surface and displays characteristics comparable to those of preneoplastic hepatocytes. PMID- 1618472 TI - Biglycan and decorin gene expression in normal and fibrotic rat liver: cellular localization and regulatory factors. AB - The expression of genes encoding the core proteins of the novel small chondroitin/dermatan sulfate proteoglycans decorin and biglycan was studied in the livers of normal rats and in liver tissue during fibrogenesis induced by prolonged bile-duct ligation and thioacetamide poisoning. The cell types responsible for the expression of these transcripts and some key regulatory factors were identified. Both biglycan and decorin messenger RNAs were detected in normal liver tissue. Their relative abundance increased strongly during liver fibrogenesis, reaching highest levels in cirrhotic tissue 8 wk after common bile duct ligation and after 12 wk of peroral thioacetamide administration, respectively. Specific proteoglycan transcripts were almost absent in hepatocytes from normal and regenerating liver, and only trace amounts were observed in freshly isolated and cultured Kupffer cells. Fat-storing cells clearly expressed both biglycan and decorin transcripts. The steady-state levels of their messenger RNAs increased threefold (biglycan) and fourfold (decorin) during primary culture. Myofibroblastlike cells (transformed fat-storing cells after the second passage) contained dramatically reduced levels of decorin messenger RNA and also lower levels of biglycan messenger RNA compared with primary cultures. These changes of core protein messenger RNA expression were not reflected by the synthesis rates of medium proteoglycans labeled with 35S as Na2SO4, in particular that of medium chondroitin sulfate. Transiently acidified (but not native) conditioned media from Kupffer cells and myofibroblastlike cells and transforming growth factor-beta 1 enhanced the relative abundances of biglycan and decorin messenger RNAs up to five times in primary-cultured fat-storing cells. Biglycan and decorin in myofibroblastlike cells did not respond to these stimuli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618474 TI - Urea and protein synthesis in cold-preserved isolated rat hepatocytes. AB - We used an isolated-hepatocyte model to study how hypothermic storage (simulating liver preservation) affects metabolism after prolonged preservation. Rat hepatocytes were stored in the University of Wisconsin solution for up to 72 hr. After each day of storage, protein synthesis, urea synthesis, ATP content and lactate dehydrogenase release were determined in rewarmed (37 degrees C) and oxygenated hepatocytes. Protein synthesis ([3H]-leucine incorporation into protein) was depressed by 16% +/- 4%, 54% +/- 6% and 69% +/- 4% after 24 hr, 48 hr and 72 hr, respectively. Urea synthesis, ATP synthesis and lactate dehydrogenase release were similar to those in control hepatocytes (no preservation). Fasting of the rats before isolation of hepatocytes caused more rapid loss of protein-synthesis capabilities (59% in 24 hr) with no significant loss of lactate dehydrogenase, urea synthesis or ATP synthesis. Hepatocyte viability (lactate dehydrogenase release) as judged by membrane permeability, ATP synthesis and potassium content can be maintained after up to 6 days of cold storage. However, protein synthesis is depressed after only 48 hr of cold storage. Thus hypothermic storage of the liver causes a change in the metabolic capabilities of the hepatocytes, and the timing of the loss of protein synthesis is similar to the limits of successful cold storage of the whole liver (48 hr). Thus a limit to long-term storage of the liver may be related to loss of protein synthesis. In liver transplantation, one indication of poor preservation is a decrease in serum albumin and clotting factors with increased tissue edema and bleeding diathesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618475 TI - Brain water and acute liver failure: the emerging role of intracranial pressure monitoring. PMID- 1618476 TI - Transforming growth factor-beta: the elusive hepatic chalone? PMID- 1618477 TI - Pumping ions: regulation of intracellular pH in hepatocytes. PMID- 1618478 TI - Quantitating hepatic encephalopathy in rats after portacaval anastomosis. PMID- 1618479 TI - Recurrence of alveolar echinococcosis in the liver graft after liver transplantation. PMID- 1618480 TI - Fulminant hepatitis related to transmission of hepatitis B variants with precore mutations between spouses. AB - A precore defective variant of hepatitis B virus has been indicated to cause fulminant hepatitis in various instances such as intrahospital outbreaks or mother-to-child transmission of hepatitis B virus. To learn whether similar variants are involved in interspouse transmission, we analyzed three cases of fulminant hepatitis B that developed in formerly healthy subjects whose only exposure to hepatitis B virus was contact with their longtime spouses, who were carriers of HBV and positive for antibody to HBe. The DNA clones for precore and S genes were propagated from patients and spouses and sequenced. Because of the conservation of S-gene sequences and the identity of subtypes between patient and spouse, it was suggested that patients were infected with hepatitis B virus from their spouses, not from other sources. A TGG-to-TAG mutation at the 28th codon of the precore gene of hepatitis B virus was commonly observed in all DNA clones from patients with fulminant hepatitis and from their spouses. A 29th-codon GGC to-GAC mutation was additionally evident in DNAs from one patient-and-spouse couple. A significant rise in the circulating hepatitis B virus concentration was transiently observed in the index spouse of this case just before development of fulminant hepatitis in her husband. The increase in circulating HBV DNA was associated with a rise in abundancy of variants with mutations at both the 28th and 29th codons, compared with variants with only a 28th-codon mutation. The double mutation in hepatitis B virus DNA may either help the virus escape immune surveillance or replicate at a higher rate than before. PMID- 1618481 TI - Hepatitis B virus DNA in peripheral-blood mononuclear cells in chronic hepatitis B after HBsAg clearance. AB - In this study, peripheral-blood mononuclear cells from patients with chronic hepatitis B and spontaneous or therapy-induced disappearance of HBsAg were examined for HBV DNA. Samples were evaluated by in situ hybridization and polymerase chain reaction both before and after clearance of HBsAg. By in situ hybridization, positive signals were observed in 2 of 13 samples collected after HBsAg loss, in 8 of 15 samples before HBsAg loss and in 0 of 4 control patients without serological markers of active or prior HBV infection. When polymerase chain reaction analyses were performed, HBV DNA was detected in 5 of 12 HBsAg negative samples and 10 of 15 HBsAg-positive samples from the study group. Testing of mononuclear cells after disappearance of HBsAg revealed that two of eight patients were HBV DNA positive by in situ hybridization and by polymerase chain reaction, whereas two additional patients were positive by polymerase chain reaction alone. Mononuclear cell-associated HBV DNA was detected between 2 and 9 mo after the disappearance of circulating HBsAg by in situ hybridization and as long as 4 yr later by polymerase chain reaction. These data indicate that patients who have undergone HBsAg seroconversion may nonetheless harbor HBV DNA in their peripheral-blood mononuclear cells for prolonged periods. PMID- 1618482 TI - Ischemic-type biliary complications after orthotopic liver transplantation. AB - Nonanastomotic biliary strictures that involve only the biliary tree of the graft occur after orthotopic liver transplantation in patients with hepatic artery thrombosis, chronic ductopenic rejection and ABO blood group incompatibility. This complication may also occur in the absence of these known risk factors. The major focus of our study was to evaluate the risk factors for nonanastomotic biliary stricturing of unknown cause after orthotopic liver transplantation. Results demonstrate that the development of biliary strictures is strongly associated with the duration of cold ischemic storage of allografts in both Euro Collins solution and University of Wisconsin solution. Results also demonstrate that strictures are not associated with the type of biliary reconstruction, the primary liver disease, cytomegalovirus infection, allograft rejection or the presence of a positive lymphocytotoxic crossmatch. More recently, we have markedly reduced the occurrence of nonanastomotic biliary stricturing by decreasing the ischemia time of our allografts. Thus nonanastomotic biliary strictures appear to be the result of the ischemia/reperfusion-induced tissue injury associated with the harvest and implantation of allografts. PMID- 1618483 TI - Isolation and characterization of the mannose receptor from human liver potentially involved in the plasma clearance of tissue-type plasminogen activator. AB - Various studies have shown that mannose receptors rapidly eliminate glycoproteins and microorganisms bearing high mannose-type carbohydrate chains from the blood circulation. The purpose of this study was to characterize the mannose receptor in the liver, which in vivo is involved in the rapid clearance of tissue-type plasminogen activator from the circulation. Human liver membranes were solubilized in Triton X-100, and the solution was applied to a tissue-type plasminogen activator Sepharose column. Bound proteins were eluted with ethylenediaminetetraacetate (10 mmol/L). A second, similar purification step rendered a single liver protein of 175,000 daltons. A combination of ligand blotting and a chromogenic assay for tissue-type plasminogen activator demonstrated that the identified liver protein is a mannose receptor because it bound tissue-type plasminogen activator, this tissue-type plasminogen activator binding being fully inhibited by 0.2 mol/L D-mannose. Western-blot analysis revealed that the isolated liver protein is immunologically identical to the human mannose receptor from placenta. Treatment of the liver protein and the placenta mannose receptor with trypsin yielded the same pattern of proteolytic degradation products as identified on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. We conclude that the physiologically relevant mannose receptor for tissue-type plasminogen activator clearance isolated from human liver is immunologically and structurally similar to or identical with the human mannose receptor isolated from placenta. PMID- 1618484 TI - Reversal of fulminant hepatic failure using an extracorporeal liver assist device. AB - Liver transplantation is currently the only effective therapy for patients with fulminant hepatic failure. The availability of an artificial liver could bridge these patients through the relatively brief crisis period and allow their own livers to regenerate, providing a more favorable outcome and sparing the trauma and expense of transplant. We have developed a device consisting of a highly differentiated human liver cell line cultured in a hollow fiber cartridge. This device is capable of supporting dogs with acetaminophen-induced fulminant hepatic failure for a period long enough for their own livers to resume function. Even though liver function tests such as albumin and prothrombin time became extremely abnormal during the course of the experiment, the dogs did not become encephalopathic. Two of the three treated animals recovered sufficient liver function after 42 to 48 hr of treatment that they could be disconnected from the device, and they survived the experiment. Histological results and serum ALT levels suggest that the device affected the course of the disease in two animals, allowing recovery of hepatocytes that would otherwise have lysed. In the third animal, regenerative nodules demonstrated that, even in the presence of severe liver injury, the device was capable of supporting total liver function. PMID- 1618485 TI - Interrelationships of bile acid and phospholipid fatty acid species with cholesterol saturation of duodenal bile in health and gallstone disease. AB - The relative amount of cholesterol and the fatty acid composition of phosphatidylcholines in bile can be influenced by the bile acid species secreted. To search for a contribution of secondary bile acids and of phosphatidylcholines to supersaturation of bile in gallstone disease, we compared the relative amount of cholesterol and the biliary composition of bile acids and of phospholipid fatty acids in cholecystokinin-stimulated duodenal bile of 22 female gallstone patients and 16 healthy controls and analyzed the interrelationships of these bile constituents. Gallstone patients had higher molar percentages of cholesterol than did controls (10.2 +/- 3.2 vs. 6 +/- 1.5 mol%; p less than 0.001) and demonstrated a trend toward larger fractions of deoxycholic and lithocholic acids. By linear models, variation of cholesterol saturation could be predicted (p less than 0.001) up to 53% by the bile acid pattern and up to 81% by the fatty acid pattern of phospholipids. Linear path analysis (goodness-of-fit index = 0.973) confirmed the tight relationship between phospholipid fatty acids (positive: oleic, arachidonic; negative: linoleic, palmitoleic) and the relative amount of cholesterol; more than half the influence of cholic, deoxycholic and lithocholic acids on the relative amount of cholesterol could be explained indirectly by their influence on the phospholipid fatty acid pattern. We conclude that the relationships examined by path analysis support the working hypothesis that secondary bile acids contribute to supersaturation of bile mainly by changing the fatty acid pattern of the secreted phospholipids (presumably the pattern of phosphatidylcholines), which increases the molar ratio of cholesterol/phospholipids in bile. PMID- 1618486 TI - A prospective randomized trial comparing repeated endoscopic sclerotherapy and propranolol in decompensated (Child class B and C) cirrhotic patients. AB - A prospective randomized study was conducted to compare the efficacy of long-term endoscopic sclerotherapy vs. propranolol in Child class B and C patients with variceal bleeds within the 30 days before the study. Forty-five and 46 patients were randomized to receive sclerotherapy and propranolol, respectively, after preentry stratification for Child scores. Sclerotherapy was administered with 1% polidocanol at 10-day intervals until obliteration of varices was achieved. Propranolol was administered to achieve a reduction in resting pulse rate of 25%. Rebleeding occurred in 19 patients undergoing sclerotherapy and in 31 receiving propranolol (p less than 0.05). The number of episodes of rebleeding was higher (p less than 0.05) in the propranolol group (n = 64) than in the sclerotherapy group (n = 35). The mean bleeding risk factor, number of hospitalizations for rebleeding and blood transfusion requirement were also significantly higher in the propranolol-treated patients. The median bleed-free period was more than 36 mo in the sclerotherapy group and 2.5 mo in the propranolol group (p less than 0.01). The median survival time was significantly longer in the sclerotherapy group (greater than 36 mo) than in the propranolol group (greater than 24 mo). We conclude that in decompensated cirrhotic patients, long-term endoscopic sclerotherapy is superior to propranolol in preventing rebleeding and improving survival. PMID- 1618487 TI - Differences in apolipoprotein (a) polymorphism in west Greenland Eskimos and Caucasian Danes. AB - Previous studies in Greenland suggest that death rates from ischemic heart disease [IHD] are lower in Eskimos than in Danes and other Caucasian populations. This has been explained by a high intake of n-3 polyunsaturated fatty acids with beneficial effects on blood lipids and hemostasis. In other populations, lipoprotein(a) [Lp(a)] is associated with IHD, plasma concentrations of Lp(a) being genetically determined to a major extent. We have compared Lp(a) concentrations and apo(a) phenotypes in 120 Greenlandic Eskimos with those in 466 Danish men. The median Lp(a) concentration in Eskimos (8.7 mg/dl;[95% CI 6.5 10.7]) was not significantly different from that in Danes (6.3 mg/dl; [95% CI 5.2 7.0]), whereas the 90th percentile was significantly higher among Danes: 46.36 mg/dl; [95% CI 43.0-54.3] vs. 27.6 mg/dl [95% CI 20.7-36.9]. In 20% of the Danes, but in only 8% of the Eskimos (P = 0.009), the concentration of Lp(a) exceeded 30 mg/dl. The difference is probably explained by a low frequency of the low molecular weight apo(a) phenotypes among Eskimos, since the apo(a) isoforms F and B were absent, and the S1 and S2 types were present in only 3.3% of Eskimos. In contrast, these apo(a) isoforms were present in 26.6% of the Danes in either single-band or double-band phenotypes. The pattern of apo(a) polymorphism found in this study could provide part of a genetic explanation for the putative low rates of IHD in Eskimo populations. PMID- 1618488 TI - Simple repeat sequences on the human Y chromosome are equally polymorphic as their autosomal counterparts. AB - The human genome contains a large number of interspersed simple repeat sequences that are variable in length and can therefore serve as highly informative, polymorphic markers. Typing procedures include conventional multilocus and single locus probing, and polymerase chain reaction aided analysis. We have identified simple sequences in a cosmid clone stemming from the human Y chromosome and consisting of (gata)n repeats. We have compared these with two equivalent simple repeat loci from chromosome 12. After amplifying the tandemly repeated motifs, we detected between four and eight different alleles at each of the three loci. Codominant inheritance of the alleles was established in family studies and the informativity of the simple repeat loci was determined by typing unrelated individuals. The polymorphisms are suitable for application in linkage studies, practical forensic case work, deficiency cases in paternity determination, and for studying ethnological questions. The mutational mechanisms that bring about changes in simple repeats located both on the autosomes and on the sex chromosomes, are discussed. PMID- 1618489 TI - Mutation analysis and prenatal diagnosis in a Lesch-Nyhan family showing non random X-inactivation interfering with carrier detection tests. AB - A nonsense mutation at the CpG-site in the codon for Arg(169) in the gene for hypoxanthine phosphoribosyltransferase (hprt) was identified by genomic polymerase chain reaction (PCR) and DNA sequencing in cultured fibroblasts from two brothers with Lesch Nyhan's syndrome. The recurrence of mutation at this CpG site in several unrelated Lesch-Nyhan families suggests that deamination of 5 methylcytosine is a possible mechanism for mutagenesis. The level of hprt-mRNA in the fibroblasts of the patients was similar to that in healthy controls, whereas hprt-enzyme activity was not detectable. The mutation in this family was also identified in five female relatives and prenatally in a male fetus. Unexpectedly, results from hair follicle analyses and fibroblast selection studies in 8 azaguanine and 6-thioguanine medium showed a non-carrier phenotype in three of the female heterozygotes, whereas X-inactivation mosaicism was demonstrated in one heterozygote. A possible explanation for the apparent non-random X inactivation in this family is the co-existence of the hprt mutation with an undefined X-linked lethal mutation. This observation is of practical relevance for carrier detection in other Lesch-Nyhan families. PMID- 1618491 TI - The segregation of a translocation t(1;4) in two male carriers heterozygous for the translocation. AB - We examined the meiotic segregation pattern of a t(1;4)(p36.2;q31.3) reciprocal translocation in two male cousins heterozygous for the translocation. The wife of subject 1 had four recognized spontaneous abortions and two carrier daughters, and the wife of subject 2 had three recognized spontaneous abortions and no live born children. The results showed that subject 1 had an imbalance rate of 54% and subject 2 had an imbalance rate of 61% with respect to the translocation. This was not statistically different (P = 0.3174) and the 95% confidence intervals overlapped for each segregation type. The sex ratio of X- and Y-bearing sperm was not statistically different than the expected 50%. The rate of structural abnormalities was 11.3% in subject 1 and 17.8% in subject 2. Both of these values were above the range of control subjects in our lab, but only subject 2's value fell outside the 95% confidence interval for the control population. PMID- 1618490 TI - Deletions in the dystrophin gene: analysis of Duchenne and Becker muscular dystrophy patients in Quebec. AB - We have analyzed patient DNA samples in 77 unrelated Duchenne (DMD) and Becker (BMD) muscular dystrophy families, 73 of which were of French Canadian origin. We show that the frequency (68%) and distribution of deletions within the dystrophin gene was neither random nor unique in this population. We localized 33% of the deletions to the proximal portion of the dystrophin gene while 63% involved the exons spanning introns 43 through 55 with breakpoint clusters occurring within introns 44 and 50. Whether the dystrophin open reading frame (ORF) is maintained constrains the distribution of DMD/BMD deletions such that BMD deletions tend to be strikingly homogeneous. Finally, the conservation of the dystrophin ORF and the severity of the clinical phenotype were concordant in 95% of the DMD/BMD deletions documented by this work. PMID- 1618492 TI - Familial pericentric inversion (3)(p12q24). AB - A large kindred with a familial pericentric inversion of chromosome 3, (p12q24), was found after an investigation initiated by a young female with three spontaneous first-trimester abortions. Altogether 22 (33%) inversion carriers were discovered, 9 females and 13 males. 6 women and 9 men were included in the fertility and segregation analyses because they were all either sexually mature or past maturity. The abortion frequency was below the average European rate in both the inversion carrier group and the cytogenetically normal relative group; 6%:3%, respectively. The mean numbers of pregnancies and live births (1.8-3.1) did not vary significantly in the two comparison groups. The segregation analysis among the inversion carriers showed a good correspondence to the theoretical 1:1 ratio (16:13). Males and females contributed equally. No duplication/deletion syndromes have been found in the kindred; all family members are phenotypically normal. We report a balanced familial pericentric inversion with no adverse effects. This chromosome aberration could be an example of a harmless chromosome polymorphism. PMID- 1618493 TI - Genetic and biochemical heterogeneity in patients with the rhizomelic form of chondrodysplasia punctata--a complementation study. AB - The genetic relationship between 10 patients with clinical manifestations of rhizomelic chondrodysplasia punctata (RCDP) was studied by complementation analysis after somatic cell fusion. Biochemically, 9 out of the 10 patients were characterized by a partial deficiency of acyl-CoA: dihydroxyacetone phosphate acyltransferase (DHAP-AT) and an impairment of plasmalogen biosynthesis, phytanate catabolism and the maturation of peroxisomal 3-oxoacyl-CoA thiolase; 3 oxoacyl-CoA thiolase was strongly reduced in the peroxisomes of these patients. Fusion of fibroblasts from these 9 patients with Zellweger fibroblasts resulted in complementation as indicated by the restoration of DHAP-AT activity, plasmalogen biosynthesis, and punctate fluorescence after staining with a monoclonal antibody to peroxisomal thiolase. No complementation was observed after fusion of different combinations of the 9 RCDP cell lines, suggesting that they belong to a single complementation group. The tenth patient was characterized biochemically by a deficiency of DHAP-AT and an impairment of plasmalogen biosynthesis. However, maturation and localization of peroxisomal thiolase were normal. Fusion of fibroblasts from this patient with fibroblasts from the other 9 patients resulted in complementation as indicated by the restoration of plasmalogen biosynthesis. We conclude that mutations in at least two different genes can lead to the clinical phenotype of RCDP. PMID- 1618494 TI - Paracentric inversion 11q in Canadian Hutterites. AB - Four Canadian Hutterite families were found to carry the paracentric inversion inv(11)(q21q23). We did not document any adverse effects that could be directly attributable to this inversion. It is possible that the mutation that caused this inversion is the same mutation hypothesized as the cause of the inversion in families from the Netherlands. PMID- 1618495 TI - Single-strand conformational polymorphisms (SSCP): detection of useful polymorphisms at the dystrophin locus. AB - We searched for DNA polymorphisms in seven amplified fragments of the dystrophin gene. Three fragments exhibited variable mobilities during nondenaturing strand separating gel electrophoresis (SSGE). These variants were due to single base changes (three transversions and one transition). Three were intronic (upstream from exons 17, 15, and 48) and one was in exon 48. The frequencies of these sequence variants were determined in a sample of 54 normal X chromosomes of Caucasian origin. One of these DNA polymorphisms was observed in every 650 bp tested and the average heterozygosity was 0.05% per base pair (0.08% if exons were excluded). Such a detection density and the fact that single-strand conformational polymorphisms do not depend on the presence of any specific sequence makes them especially valuable as genetic markers. In the dystrophin locus this approach could allow simultaneous detection of frequent deletions. PMID- 1618496 TI - The Kell blood group locus is close to the cystic fibrosis locus on chromosome 7. PMID- 1618497 TI - Molecular diagnosis of the transthyretin (TTR) Met111 mutation in familial amyloid cardiomyopathy of Danish origin. AB - Familial amyloid cardiomyopathy in a Danish kindred is associated with a specific mutation (Met for Leu111) in the transthyretin (TTR) gene, causing the loss of a recognition site for the restriction enzyme DdeI in the gene. We describe a diagnostic test for the molecular detection of this mutation. A sequence of the TTR gene containing the mutation was amplified by the polymerase chain reaction from isolated genomic DNA of two affected patients and several controls. DdeI digestion of the amplified DNA from the patients revealed 3 bands by gel electrophoresis, whereas amplified DNA of the controls showed only 2 bands, consistent with complete digestion. Thus, the assumed heterozygous TTR Met111 mutation was confirmed in the affected patients. PMID- 1618498 TI - Data on the interaction of ABO blood groups and the haptoglobin system. PMID- 1618499 TI - [K.7 K.pote: an original experience in the promotion of condoms among youths]. AB - The CRIPS is a specialised AIDS prevention center in the Paris metropolitan region. The Paris metropolitan region regroups 10 million inhabitants in its urban zone. This region is one of the most affected areas in Europe by AIDS and HIV infection, and contains more than 50 percent of the AIDS cases in France. As of June 30, 1991, the rate of declared AIDS cases in Paris was 8 for every one thousand inhabitants. At the beginning of the epidemic, AIDS basically concerned homosexuals in the center of Paris. Today, more and more young heterosexual drug users are affected. Adolescents from a low socio-economic background are often at risk of marginalization from the mainstream of society and thus at risk to become part of this new HIV affected population. They are often not reached by mass media, general public campaigns. In France, very little information materials are directly targetted to this young, socio-economically disadvantaged population. The CRIPS set out to devise a new prevention tool which would target young males from this population, particularly those in the 15-20 year age group. In preparation for the project, six months were spent on field research in the neighborhoods where the young people lived, worked and socialized. Interviews were held with young people themselves and adults in the area, particularly bar men and others working where the youth socialized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618500 TI - A dutch smoking prevention project: an overview. PMID- 1618502 TI - The Barcelona Smoke-free Olympics project. PMID- 1618501 TI - The Athoor experience. Field perspectives for implementing child survival programmes in the 90s. PMID- 1618504 TI - Transfer of the Regional Office for Europe to The Netherlands. PMID- 1618503 TI - Health education in Kupat Holim. PMID- 1618505 TI - Advocacy for health. The policy of health promotion and the role of health education in Europe in the 1990s. PMID- 1618506 TI - A world united against AIDS. PMID- 1618508 TI - World breastfeeding week. August 1-7 1992. World Alliance for Breastfeeding Action. PMID- 1618507 TI - Update: the baby-friendly hospital initiative. PMID- 1618509 TI - Dangerous myths. PMID- 1618510 TI - Leading the way to a baby-friendly world. PMID- 1618511 TI - Education for a better quality of life. PMID- 1618512 TI - Health challenges of the developed world. PMID- 1618513 TI - World health in perspective. The developing countries' point of view. PMID- 1618514 TI - Communication campaigns to change health-related lifestyles. PMID- 1618515 TI - Health and life style transition. PMID- 1618516 TI - Health and local development education. PMID- 1618517 TI - Health--united efforts. PMID- 1618518 TI - Social action for health: emerging perspectives for health education. AB - Most of the world's major health problems and premature deaths are preventable. Health technology and scientific knowledge exists to combat health problems at an affordable cost. And, health education is recognized as a viable public health intervention and a vitally important means of addressing health challenges. PMID- 1618519 TI - A tale of two programmes--a health education success story from the International Federation of Red Cross and Red Crescent Societies. PMID- 1618520 TI - Health promotion and public policy. PMID- 1618521 TI - A new configuration for the health care system of the USSR. PMID- 1618522 TI - Namibia's health policies and strategies. PMID- 1618523 TI - School health education: challenge for national and international agencies. AB - There are, in today's world, more than a billion young people of school age. Hundreds of millions of them are enrolled in the schools. They constitute the greatest single readily-reachable population group and present one of our greatest opportunities toward achieving a brighter health future. Are we availing ourselves of this opportunity? It is sad but true that too often school health education is considered as "something extra", a matter of peripheral interest, and is given low priority in school curriculum. Yet these young people--in the schools and outside them--are the parents, the citizens, the leaders of tomorrow. Theirs is the health of the future. We cannot afford to leave the health citizenship of the future to a generation only causally educated about life. PMID- 1618525 TI - Training of health educators. PMID- 1618524 TI - Health education: historic windows of opportunity. PMID- 1618526 TI - Breakthrough to nursing's early years. PMID- 1618527 TI - Imprint through the years. PMID- 1618528 TI - Diary from the eighties. PMID- 1618529 TI - Issues in the eighties. PMID- 1618530 TI - NSNA and the ANA: cooperation for the future. PMID- 1618531 TI - NSNA in the decade of the 90's. PMID- 1618532 TI - Tragedy in Mexico. PMID- 1618533 TI - A student-designed activity program for the chronically mentally ill. PMID- 1618534 TI - Phillip Shipley. PMID- 1618535 TI - Men in OB/GYN nursing: a student's enlightenment or nightmare? PMID- 1618536 TI - Surveillance of news media: a nursing responsibility. PMID- 1618537 TI - Environmental assessment of the workplace. PMID- 1618538 TI - NSNA: how it grew. 1952-1977. The first 25 years. 1977. PMID- 1618539 TI - Interview with Frances Tompkins, first NSNA Executive Director. Interview by Diane Mancino. PMID- 1618540 TI - NSNA in the 1960's. PMID- 1618541 TI - Challenges of the seventies and early eighties. PMID- 1618542 TI - Power by association: NSNA in its teens. PMID- 1618543 TI - Issues in the 70's. PMID- 1618544 TI - Conduit artery compliance and distensibility are not necessarily reduced in hypertension. AB - The goal of this study was to investigate whether the elastic behavior of conduit arteries of humans or rats is altered as a result of concomitant hypertension. Forearm arterial cross-sectional compliance-pressure curves were determined noninvasively by means of a high precision ultrasonic echo-tracking device coupled to a photoplethysmograph (Finapres system) allowing simultaneous arterial diameter and finger blood pressure monitoring. Seventeen newly diagnosed hypertensive patients with a humeral blood pressure of 163/103 +/- 4.4/2.2 mm Hg (mean +/- SEM) and 17 age- and sex-matched normotensive controls with a humeral blood pressure of 121/77 +/- 3.2/1.9 mm Hg were included in the study. Compliance pressure curves were also established at the carotid artery of 16-week-old anesthetized spontaneously hypertensive rats (n = 14) as well as Wistar-Kyoto normotensive animals (n = 15) using the same echo-tracking device. In these animals, intra-arterial pressure was monitored in the contralateral carotid artery. Mean blood pressures averaged 197 +/- 4 and 140 +/- 3 mm Hg in the hypertensive and normotensive rats, respectively. Despite the considerable differences in blood pressure, the diameter-pressure and cross-sectional compliance-pressure and distensibility-pressure curves were not different when hypertensive patients or animals were compared with their respective controls. These results suggest that the elastic behavior of a medium size muscular artery (radial) in humans and of an elastic artery (carotid) in rats is not necessarily altered by an increase in blood pressure. PMID- 1618545 TI - Increased systolic pressure in chronic uremia. Role of arterial wave reflections. AB - To assess the role of arterial wave reflections in the mechanism of systolic hypertension and altered pulsatile arterial dynamics in patients with end-stage renal disease (ESRD), 79 ESRD patients were compared with 73 age-matched control subjects with normal renal function and similar mean blood pressure. Wave reflections were investigated from the carotid pulse contour recorded by applanation tonometry using a Millar micromanometer-tipped probe. Wave reflections were quantified as the ratio (augmentation index, %) of the height of the late systolic peak to the total height of carotid pulse wave. Travel time of the reflected wave was timed from the foot of the pressure wave to the foot of the late systolic peak. Systolic and pulse pressure were increased in ESRD patients (p less than 0.001) and was not attributable to differences in left ventricular ejection pattern. The augmentation index was increased in ESRD patients (23.2 +/- 15.0 versus 9.8 +/- 15.6%; p less than 0.001) in association with a shorter travel time of reflected wave (109 +/- 24 versus 131 +/- 30 msec; p less than 0.001). Multiple regression analysis showed two principal factors associated (p less than 0.001) with the increase in augmentation index and shortened travel time of reflected wave: increased aortic pulse wave velocity and smaller stature with shorter body height in ESRD patients. The study points to the role of arterial wave reflections in the mechanisms producing alterations in pulsatile arterial dynamics in ESRD and is the first, through the mechanisms of early wave reflections, to show in humans that the increase in systolic and pulse pressures is associated with lesser body size. PMID- 1618546 TI - Renal effects of prolonged synthesis inhibition of endothelium-derived nitric oxide. AB - The aim of the present study was to investigate in conscious dogs the long-term effects of nitric oxide synthesis inhibition on glomerular filtration rate, sodium and water excretion, and plasma levels of renin and aldosterone. After a control period of 3 days, an inhibitor of endothelium-derived nitric oxide synthesis, NG-nitro-L-arginine-methyl ester, was infused for 3 consecutive days at a dose (50 ng/kg/min) that did not induce significant changes in arterial pressure (n = 6). The inhibition of nitric oxide synthesis led to a large and sustained decrease (p less than 0.05) in glomerular filtration rate of approximately 35%. This change was accompanied by a decrease (p less than 0.05) in urinary sodium excretion from 78.9 +/- 4.6 meq/day to 49.8 +/- 6.8, 60.1 +/- 4.2, and 53.5 +/- 9.0 meq/day by days 1, 2, and 3 of nitric oxide synthesis inhibition, respectively. Changes in fractional sodium excretion failed to achieve statistical significance. Nitric oxide synthesis inhibition also induced a significant and sustained decrease in urine flow rate. The decrease in glomerular filtration rate, natriuresis, and diuresis was accompanied by a 45% increase in plasma renin activity (p less than 0.05) and no change in plasma aldosterone concentration. By day 3 of the recovery period, glomerular filtration rate, natriuresis, diuresis, and plasma renin activity returned to values similar to those found during the control period. The administration of L-arginine during 3 consecutive days (5 micrograms/kg.min i.v.) did not modify any of the parameters measured but effectively prevented all the renal changes induced by the 3 days of nitric oxide synthesis inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618547 TI - Oxygen free radicals and cardiac reperfusion abnormalities. AB - Oxygen free radicals are highly reactive compounds causing peroxidation of lipids and proteins and are thought to play an important role in the pathogenesis of reperfusion abnormalities including myocardial stunning, irreversible injury, and reperfusion arrhythmias. Free radical accumulation has been measured in ischemic and reperfused myocardium directly using techniques such as electron paramagnetic resonance spectroscopy and tissue chemiluminescence and indirectly using biochemical assays of lipid peroxidation products. Potential sources of free radicals during ischemia and reperfusion have been identified in myocytes, vascular endothelium, and leukocytes. In several different experimental models exogenous free radical-generating systems have been shown to produce alterations in cardiac function that resemble the various reperfusion abnormalities described above. Injury to processes involved in regulation of the intracellular Ca2+ concentration may be a common mechanism underlying both free radical-induced and reperfusion abnormalities. Direct effects of free radicals on each of the known Ca(2+)-regulating mechanisms of the cell as well as the contractile proteins and various ionic membrane currents have been described. Free radicals also inhibit critical enzymes in anaerobic and aerobic metabolic pathways, which may limit the metabolic reserve of reperfused myocardium and contribute to intracellular Ca2+ overload. Inhibiting free radical accumulation during myocardial ischemia/reperfusion with free radical scavengers and inhibitors has been demonstrated to reduce the severity of myocardial stunning, irreversible injury, and reperfusion arrhythmias in many, but not all, studies. This evidence strongly implicates free radical accumulation during myocardial ischemia/reperfusion as an important pathophysiological mechanism of reperfusion abnormalities, although many issues remain unresolved. PMID- 1618549 TI - Pseudohypertension and the measurement of blood pressure. AB - Riva-Rocci Korotkoff (RRK) blood pressure measurements may overestimate the intra arterial pressure (IAP) in individual patients. To study pseudohypertension, defined as an overestimation larger than 10 mm Hg, we compared RRK and IAP measurements in 76 patients. These patients were considered to be at risk for pseudohypertension because of high age, hypertension, or vascular disease. RRK measurements underestimated simultaneously measured systolic IAP values by 6.0 +/ 6.5 (mean +/- SD) mm Hg, whereas simultaneous diastolic RRK readings overestimated the IAP by 1.9 +/- 5.6 mm Hg. Diastolic overestimation increased slightly with age. Vascular rigidity, as measured by counterpressure plethysmography, did not correlate with these errors. Systolic and diastolic pseudohypertension was observed in two and five patients, respectively. Pseudohypertension was only present in the group in which IAP was measured in the aorta. However, the number of patients with systolic and diastolic pseudohypertension could be increased to three and seven by using the average intra-arterial systolic and diastolic pressure during an RRK measurement or to six and 11 by using the IAP during a control period just before an RRK measurement rather than the IAP at the moment of appearance or disappearance of the Korotkoff sounds. The widely diverging prevalence of pseudohypertension described in the literature might be explained because of such different comparison techniques. PMID- 1618548 TI - Hypertension induces alternatively spliced forms of fibronectin in rat aorta. AB - Fibronectin expression was shown recently to increase in the rat aorta in response to experimental hypertension. Fibronectin is known to alter the phenotype of vascular smooth muscle and endothelial cells, and relative changes in the expression of different isoforms of fibronectin, generated by alternative splicing and distinguished by the absence or presence of inserts designated as EIIIA, EIIIB, and V, may reflect a change in cell phenotype. In the present study we examined the expression of alternatively spliced forms of aortic fibronectin during deoxycorticosterone-salt hypertension. Aortic RNA was analyzed quantitatively using Northern blot analysis and ribonuclease protection assays. Using Northern blot analysis, deoxycorticosterone-salt treatment for 21 days led to a 4.9-fold increase in EIIIA fibronectin messenger RNA, while EIIIB and V forms increased by 2.6- and 2.5-fold, respectively. As determined by ribonuclease protection assays, the percentage of fibronectin transcripts containing either EIIIA, EIIIB, or V in control aorta was 7.3%, 19%, and 40%, respectively. The percentage of EIIIA transcripts increased 42% over control levels after 21 days of deoxycorticosterone-salt treatment, whereas no proportionate change in the other alternatively spliced forms was found. Thus, all forms increased, but a selective increase in the EIIIA form was induced. Analogous increases in each of the fibronectin isoforms were found in the spontaneously hypertensive rats when compared with age-matched Wistar-Kyoto or Wistar rats, and 40-week-old animals showed increases over 10-week-old animals in all strains, consistent with an age dependent increase in aortic fibronectin expression. PMID- 1618550 TI - Hypertension and ST segment depression during ambulatory electrocardiographic recording. Results from the prospective population study 'men born in 1914' from Malmo, Sweden. AB - The aim of this study in 341 men (aged 68 years) without history of ischemic heart disease was to study the relation between hypertension and silent ischemic type ST segment depression during ambulatory long-term electrocardiographic recording and to assess the influence between these two variables on cardiovascular morbidity and mortality rates. Seventy-nine men (23%) demonstrated one or more episodes of silent ischemic ST segment depression. One hundred and sixty-seven men (49%) were considered to have hypertension (i.e., they had a diastolic blood pressure of 95 mm Hg or greater or were treated with antihypertensive therapy). Forty-nine (72%) of the 68 treated hypertensive subjects were classified as uncontrolled (i.e., their diastolic blood pressure was 95 mm Hg or greater). The occurrence of ischemic ST depression was higher in hypertensive men (28%) than in normotensive men (19%). The highest incidence of ischemic ST depression (41%) was observed in treated hypertensive men with inadequate blood pressure control. Cardiac event rate during a 53-month follow-up was 6.6% in hypertensive men and 4.6% in normotensive men. Uncontrolled treated hypertensive men had a higher event rate (14%) than hypertensive men overall. Hypertensive men with inadequate blood pressure control and who demonstrated ST segment depression had the highest event rate (25%). PMID- 1618551 TI - Clustering of cardiovascular risk factors in confirmed prehypertensive individuals. AB - Numerous studies have indicated that hypertensive subjects have an atherogenic lipoprotein pattern, hyperinsulinemia, and impaired glucose tolerance relative to normotensive individuals. These abnormalities could be due to adverse effects of certain antihypertensive agents, to pathophysiological concomitants of the hypertensive state itself, or to both. In this report, we describe the cardiovascular risk factor profile of 1,440 subjects who were normotensive and were not taking any antihypertensive medications when first examined and who subsequently participated in the 8-year follow-up of the San Antonio Heart Study. Hypertension developed in 130 subjects during the follow-up period. At baseline these prehypertensive individuals had significantly higher levels of blood pressure, fasting total and low density lipoprotein cholesterol, triglyceride, glucose, and insulin, and 2-hour glucose than those who remained free of hypertension. In addition, they had higher body mass indexes, a less favorable body fat distribution, and lower levels of high density lipoprotein cholesterol. In multiple linear regression analyses, baseline levels of triglyceride and blood pressure remained significantly higher and high density lipoprotein cholesterol remained significantly lower in the subjects who later converted to hypertension than in those who remained normotensive. Although baseline insulin levels were also higher in the prehypertensive subjects, this difference was not statistically significant. In nonobese subjects, however, those with high baseline insulin concentrations had an increased incidence of hypertension compared with those with low insulin concentrations. The present results suggest that the cluster of atherogenic changes associated with hypertension actually precede the development of the hypertensive state. PMID- 1618552 TI - Skin arteriolar responses to local temperature changes in hypertensive rats. AB - A rat skin preparation was developed to determine if the responses of the resistance vessels to local skin warming and cooling were abnormal in spontaneously hypertensive rats (SHR). A major advantage of this preparation is that all the skin resistance vessels from small arteries preceding the microcirculation to small arterioles can be studied by intravital microscopy techniques. An abdominal skin flap was reflected with intact vasculature and positioned on a temperature-controlled manifold. Diameters of small arteries and large through small arterioles were measured at normal skin temperature (35 degrees C) and after cooling to 25 degrees C and warming to 38 degrees C, there were no differences in control diameters for comparable branching orders between normotensive (Wistar-Kyoto) and hypertensive rats; however, the maximum diameter of small arteries was 13% smaller in hypertensive rats. All arteriolar branching orders possessed vascular tone that was not altered by neural blockade with tetrodotoxin. With cooling to 25 degrees C, all branching orders constricted (range, 12-37%). The largest and smallest vessels of hypertensive rats constricted almost twice as much as their normotensive counterparts. With warming to 38 degrees C, only the smallest arterioles dilated (19% in normotensive versus 43% in hypertensive rats). This study demonstrates major differences in the arteriolar branching orders that respond to local warming and cooling of nonapical skin regions in both normotensive and hypertensive rats and also shows that skin arterioles in SHR are more responsive to local temperature changes. PMID- 1618553 TI - Vascular responsiveness in rats resistant to aldosterone-salt hypertension. AB - Wistar-Furth rats have been shown to be resistant to mineralocorticoid-salt hypertension, but the mechanism for this resistance is unknown. In the current experiments, adult male Wistar and Wistar-Furth rats were given a subcutaneous aldosterone infusion (0.15 microgram/hr) for 4 weeks, and changes in blood pressure and vascular reactivity were studied. Rats received a 1% NaCl, 0.2% KCl solution to drink. After 4 weeks of aldosterone infusion, systolic blood pressure measured using a tail-cuff technique had increased by 60 mm Hg in Wistar rats but was unchanged in Wistar-Furth rats. Hypokalemia occurred in both strains in response to the aldosterone infusion. Isolated, helically cut strips of common carotid artery and aorta were prepared for isometric force recording. Cumulative concentration-response curves to norepinephrine, serotonin, KCl, calcium, nitroprusside, and acetylcholine were performed in carotid artery strips, and concentration-response curves to ouabain were performed in aortic strips. Increased vascular contractile sensitivity to KCl, ouabain, norepinephrine, and serotonin was observed in vessels from Wistar rats treated with aldosterone and salt. The same treatment in Wistar-Furth rats produced only increased vascular sensitivity to ouabain and serotonin, and these changes were of smaller magnitude than those seen in Wistar rats. Aldosterone-salt treatment produced decreased vascular sensitivity to acetylcholine and nitroprusside in both Wistar and Wistar Furth rats. These results support the hypothesis that resistance of Wistar-Furth rats to aldosterone-salt hypertension is due to resistance to the effects of aldosterone-salt treatment that normally result in increased vasoconstrictor sensitivity. PMID- 1618555 TI - A reduced elastic modulus of vascular wall components in hypertension? PMID- 1618554 TI - Aldosterone enhances angiotensin II receptor binding and inositol phosphate responses. AB - Clinical states in which angiotensin II is increased are often associated with increases in mineralocorticoids. To determine the effects of mineralocorticoids on angiotensin II action, we examined the effects of aldosterone on angiotensin II receptor expression and function in cultured rat vascular smooth muscle cells. Incubation with aldosterone resulted in concentration- and time-dependent increases in angiotensin II receptor number, without changes in binding affinity. For example, incubation with 1 microM aldosterone for 40 hours resulted in 59% increases in angiotensin II receptor number. Increases in angiotensin II receptors were dependent on protein synthesis as evidenced by the time dependency of upregulation and inhibition by cycloheximide. Incubation with aldosterone resulted in enhanced angiotensin II-stimulated phospholipase C activation, as demonstrated by increases in angiotensin II-induced inositol phosphate responses in proportion to the increases in receptor number. In addition, aldosterone prevented angiotensin II-induced downregulation of angiotensin II surface receptors and angiotensin II desensitization of inositol phosphate formation. In summary, aldosterone 1) directly increased angiotensin II receptor number, 2) increased angiotensin II-stimulated inositol phosphate responses, and 3) prevented angiotensin II-induced downregulation and desensitization. In conclusion, aldosterone may potentiate the pressor responses of angiotensin II via effects on angiotensin II receptors. PMID- 1618556 TI - Role of neutral endopeptidase in the metabolism of endothelin. AB - Endothelin is a potent vasoconstrictor produced by endothelial cells. Although endothelin has been studied extensively, little is known about its metabolism in vivo. Neutral endopeptidase EC.3.4.24.11 is reported to degrade endothelin in vitro. Therefore, we studied the effect of neutral endopeptidase inhibition by SQ29,072 on plasma levels and urinary excretion of endogenous and exogenous endothelin. Injection of 30 or 60 mg/kg SQ29,072 into anesthetized rats increased the urinary excretion of endothelin nearly 14-fold. The response was maximal during the first 30 minutes of collection and lasted for 90 minutes. The larger dose of inhibitor caused a 37-43% increase (p less than or equal to 0.05) in the plasma concentration of endothelin. Only 0.20 +/- 0.04% of the total radioactivity injected as 125I-endothelin (1 microCi; 1,308 pg) into normal rats was recovered in the urine within 30 minutes. Urinary radioactivity increased to 0.54-0.63% (p less than or equal to 0.05) of the total infused in rats pretreated with SQ29,072. Chromatographic analysis of radioactivity in the urine revealed that intact endothelin accounted for only 6-9% of the total counts in control rats but 50-56% in rats pretreated with the inhibitor. We also studied the effects of another inhibitor of neutral endopeptidase, SQ28,063, on the distribution of radioactivity in the urine, kidney, and lung of rats injected with 125I-endothelin. SQ28,063 increased urinary excretion of labeled endothelin and increased total radioactivity accumulated in the lung and kidney from 157 and 105 pg to 234 and 157 pg, respectively. Intact endothelin accounted for 90% or more of the accumulated counts in both tissues. These results indicate that 1) little circulating endothelin is cleared into the urine, 2) endothelin in the urine is likely of renal origin, and 3) neutral endopeptidase EC.3.4.24.11 plays a major role in the inactivation of endothelin. PMID- 1618557 TI - Sympathetic nervous system in high sodium one-kidney, figure-8 renal hypertension. AB - The contribution of the sympathetic nervous system and vasopressin to the maintenance of arterial pressure was investigated in high sodium-fed rats 4 weeks after the induction of one-kidney, figure-8 renal wrap hypertension. Arterial pressure was significantly greater in renal-wrapped rats than in sham-operated animals. The contribution of the sympathetic nervous system was assessed functionally by measuring the arterial pressure response to ganglionic blockade and estimating the apparent rate of release of norepinephrine. The contribution of vasopressin was assessed by administration of the vascular antagonist d(CH2)5Tyr(Me)-AVP. Whole-animal vascular responsiveness and cardiac baroreceptor reflex sensitivity were determined by graded intravenous bolus injections of angiotensin II, vasopressin, and phenylephrine. Hypertensive rats demonstrated an exaggerated reduction in arterial pressure to autonomic blockade before and after blockade of vascular vasopressin receptors. There was a significant 27% increase in the apparent rate of release of norepinephrine into the plasma. Administration of d(CH2)5Tyr(Me)-AVP did not affect arterial pressure when given alone. However, after ganglionic blockade, inhibition of the vasopressin system elicited similar falls in blood pressure in both normotensive and hypertensive rats. Arterial pressure dose-response effects of phenylephrine, angiotensin II, and vasopressin were similar between renal-wrapped and sham-operated animals; however, cardiac baroreceptor reflex sensitivity was suppressed in the hypertensive rats. These studies indicate that the maintenance of arterial pressure in chronic, high sodium renal-wrap hypertension is associated with an augmented sympathetic nervous system function. PMID- 1618558 TI - Femoral shaft fractures treated with plate fixation and interlocked nailing: a comparative retrospective study. AB - In a retrospective study, the results of 39 patients with fresh unilateral femoral shaft fractures were studied: 19 had been treated with an AO interlocking nail and 20 with an AO plate. The preoperative characteristics of both groups were similar. The interlocking nail procedure took significantly longer (P = 0.002, Wilcoxon's test) and was associated with technical faults in seven patients. Full weight-bearing was allowed significantly earlier (P = 0.001, Wilcoxon's) in the interlocking nail group. Delayed union was observed in three patients in the plate osteosynthesis group but was not encountered in the interlocking nail group. Cancellous autogenous bone grafting was performed seven times during or after plating, but was not necessary in the interlocking nail group. Two cases of osteitis arose after plating and none after interlocked nailing. At follow-up, one patient in each group was suffering from serious complaints. CONCLUSION: The interlocking nail procedure took longer than plating, but allowed earlier full weight-bearing. The final results were similar in both groups of patients. PMID- 1618559 TI - Treatment of fracture of the shaft of the femur in total hip arthroplasty by a combination of a Kuntscher nail and a modified cemented Charnley stem. AB - Eight cases of fracture of the femoral shaft in total hip arthroplasty were treated by a combination of a Kuntscher nail and a modified Charnley stem with cement. Radiological union was achieved in all patients at an average of 8 months. PMID- 1618560 TI - Herbert screw: results of a single-centre trial. AB - We report the results of a single-centre trial of the Herbert screw in the treatment of acute fractures, fracture-dislocations and non-unions of the carpal scaphoid. In the trial, 22 patients were studied with a maximum follow-up of 2.5 years. Of the patients, 84 per cent had minimal or no pain, and 94 per cent were happy with their result or significantly improved. There was an average loss of 34 per cent of radial deviation of the wrist and of 10 per cent in cylinder grip strength. On radiographic examination, 86 per cent achieved satisfactory union. However, only 73 per cent of type D2 fractures united. Overall, the subjective and objective clinical results achieved were more satisfactory than the radiographic results would suggest. PMID- 1618561 TI - Subtrochanteric fracture: fixation using the AO tibial nail. AB - We describe an alternative fixation for the pure uncomminuted subtrochanteric fracture by using the AO tibial nail. There were no intraoperative complications in 24 fractures with this method. The fractures healed within 4 months postoperatively in 18 non-pathological fractures that could be followed up. There were minor complications, including 10 degrees external malrotation in one case and varus angulation after nail breakage in another. The nails were removed in seven healed fractures without problems. Two pathological fractures which were stabilized by the AO tibial nail, combined with the use of bone cement to fill the bone defect, were able to have early postoperative ambulation without any problems with the fixing device. PMID- 1618562 TI - Humeral shaft fractures treated by interlocking nailing: a preliminary report on 16 patients. AB - A series of 16 selected patients with humeral shaft fractures were operated on using the Seidel interlocking nail. At the follow-up 5.5 months later, solid union was obtained in 13 of the 14 survivors. In these 13 patients the result was classified as excellent or good, even though impingement was seen in four patients; no other complications were encountered. PMID- 1618563 TI - Plating of fresh clavicular fractures: results of 122 operations. AB - A total of 131 fractures of the clavicle were operated on in 129 patients. There was no bony infection or infected pseudarthrosis. Four clavicles refractured after removal of the plate and five operations led to pseudarthroses which were successfully treated by reoperation. Radiological and clinical results in the majority of the re-examined patients were excellent. Indications, operative technique and causes of poor results are described. PMID- 1618564 TI - Preoperative traction in patients with hip fractures. AB - A series of 80 patients with cervical, trochanteric or subtrochanteric hip fractures were randomized to either treatment without traction, skin traction, or skeletal traction during the 1883 h between admission and operation. The institution of skin or skeletal traction was not particularly painful for the patient, but we found no indication that either was of discernible benefit. The number of analgesic medications needed was no higher in patients without traction. We conclude that traction should not be administered routinely to patients awaiting operation for hip fracture. PMID- 1618565 TI - Fracture bracing the humerus. AB - The use of humeral fracture braces has become our preferred method of treatment for fractures of the shaft of the humerus. These braces are easy to apply and adjust; the patient's acceptance of this method of treatment is high. We compared this method of treatment with the traditional method of plaster U-slab immobilization. A group of patients treated with a plaster U-slab were matched for type and level of fracture with a group treated with a humeral fracture brace and compared with regard to fracture healing and functional outcome. There was no difference between groups for healing time and final alignment of the fracture. However, there was a greater range of elbow motion at the time of union in the fracture brace group (11 degrees-126 degrees) compared with the U-slab group (50 degrees-119 degrees P less than 0.05). These results confirmed that humeral fracture bracing permits greater functional use of the limb without affecting fracture healing and alignment. PMID- 1618566 TI - Helicopter doctors? AB - All roadside procedures carried out by doctors of the Royal London Hospital Helicopter Emergency Medical Service were recorded. Of 100 injured patients treated consecutively, 68 patients required 73 treatments or procedures that were beyond the current training of the ambulance paramedic in the United Kingdom. Doctors are therefore an essential part of HEMS operations and allow earlier live saving medical intervention in the prehospital phase of care. PMID- 1618567 TI - The Johannesburg Hospital mobile anaesthesia service. AB - At a teaching hospital such as the Johannesburg Hospital with an air ambulance service, the need may arise for the administration of an anaesthetic outside the hospital. The occurrence of just such an event prompted the authors to review the literature regarding anaesthesia in adverse circumstances and to assemble, in a portable container, the equipment and drugs considered necessary to cope with the situation. In addition, the responsible anaesthetic personnel are receiving training in the use of the equipment and techniques required. PMID- 1618568 TI - Return to work of road accident victims claiming compensation for personal injury. AB - Road accidents resulting in personal injury are an increasing cost to society. This study is based on 609 accident victims (of whom 521 survived injury) who were in employment when injured and whose claims for personal injury were settled for 5000 pounds or more by one insurance company over 2 years. It examines survivors' residual disablement, return to work and involvement with rehabilitation services. Data on a representative sample of 101 cases are analysed in more detail to identify possible 'predictors' of return to work. Both univariate and stepwise logistic regression analysis suggest that return to work is less associated with clinical variables, on which much medical advice on return to work is based, than with such other variables as time off work, absence of psychological problems and younger age. Very low rates of referral to rehabilitation may indicate that a rehabilitative approach to cost containment is underutilized in comparison with the traditional emphasis on preventive measures and enhanced medical treatment. More effective rehabilitation, however, may require new approaches to clinical case management, especially in orthopaedic departments where most personal injury claimants are treated. PMID- 1618569 TI - Arthroscopic management of tibial plateau fractures. AB - Ten tibial plateau fractures treated arthroscopically are reported. In eight cases, closed internal fixation was performed under arthroscopic control while in another two patients, arthroscopic washout alone was undertaken. Only one case required external splintage (a cast brace), the remainder being mobilized non weight-bearing without plaster immediately after the operation. The results were good. We suggest that the arthroscope is a useful tool in the treatment of these fractures and provides information not otherwise available. There is a low morbidity, inpatient stay is short and early joint movement can be encouraged. PMID- 1618570 TI - Plastic bullets: significant risk of serious injury above the diaphragm. AB - A series of 123 patients who attended a district general hospital in Belfast over a 14-year period from 1975, sustained 126 plastic bullet injuries, resulting in one death and several serious injuries. This report shows the significant association of serious injury and/or death from plastic bullets in which the impact is above diaphragmatic level. PMID- 1618571 TI - Diagnostic peritoneal lavage: it's red but is it positive? AB - The aim of this study was to ascertain whether qualitative assessment could accurately determine a concentration of 100,000 RBC/mm3 in simulated peritoneal lavage fluid. The results show that the qualitative methods used are inaccurate and do not reliably predict a red cell concentration of 100,000 per mm3. We therefore recommend that the red cell concentration of peritoneal lavage fluid is always measured before the result is considered 'positive'. PMID- 1618572 TI - Effect of an algorithm on the treatment of knee injuries. AB - An audit was performed of the treatment of patients presenting with acute knee injuries to the accident and emergency department of a district general hospital. This showed that for patients requiring follow-up the majority were reviewed by the casualty officers themselves in the accident department, with the result that definitive diagnosis and treatment for patients with continuing symptoms was often delayed. Once the current treatment had been discussed at an audit meeting, a protocol (in the form of an algorithm) of the treatment of knee injuries was produced. A further audit was performed after the protocol had been in use. This demonstrated that the protocol was effective in encouraging the casualty officers to seek the help of more senior members of staff and also reduced the time taken to definitive diagnosis and treatment. PMID- 1618573 TI - Stage diving injuries. PMID- 1618574 TI - Gluteal compartment syndrome following drug overdose. PMID- 1618575 TI - Shoulder stabilization following traumatic scapulectomy. PMID- 1618576 TI - Traumatic dislocation of the lumbar spine at two levels. PMID- 1618577 TI - Post-traumatic unilateral lumbosacral ligamentous instability. PMID- 1618578 TI - Rammed by a ramp causing low-velocity sternal fractures. PMID- 1618579 TI - Bird strike at 140 mph! PMID- 1618580 TI - Scaphoid fractures and wrist pain. PMID- 1618581 TI - Prognostic factors in soft tissue injuries of the cervical spine. PMID- 1618583 TI - Social status of DUI offenders in jail. AB - It has been argued that DUI (driving under the influence) is an offense of the economically privileged, which suggests that DUI offenders may be different from other offenders. Studies of DUI arrestees and jail inmates, however, suggest they have more extensive criminal histories than other licensed drivers and similar criminal histories to other jail inmates. This study utilizes data from a representative national survey of over 5,000 jail inmates to compare jailed DUI offenders with other offenders on social characteristics, prior criminality, drug use, and alcohol use. The purpose of these comparisons is to determine whether DUI inmates represent a distinct "class" of offender for whom jail is a new experience. The implications of this distinction for policies which mandate jail time for DUI offenders are discussed. PMID- 1618582 TI - The drinking-smoking syndrome and social context. AB - Drinking and smoking concurrence is examined in a national sample of 6,072 respondents. Results indicate that the two addictive behaviors are synergistically associated in the general population: persons who both drink and smoke tend to drink to a greater extent than nonsmokers; drinkers smoke more than nondrinkers and smokers drink more than nonsmokers. As predicted, a multivariate analysis of drinking and smoking covariance was significantly correlated with social group affiliation, both across the life span and proportionately among men and women. The social context of interpersonal relationships may therefore be a critical factor in the process of pharmacological conditioning and environmental reinforcement of the drinking and smoking habits. This report confirms the strong drinking and smoking covariation found among social drinkers and heavy alcohol consumers in clinical and experimental studies, suggesting that drinking and smoking may also be interrelated in the rehabilitative process. Finally, it is suggested that the present investigation extends the research literature on the drinking and smoking syndrome in several important respects. Various implications of the study are discussed. PMID- 1618584 TI - Trends in illicit drug use in the United States: conflicting results from national surveys. AB - Data from several national studies lead to divergent conclusions regarding trends in illicit drug use in the United States. Two major population studies point to a downturn in drug use dating to the late 1970s. However, a study of drug-related deaths and hospital emergency room visits shows increases in these events in recent years. Studies also show drug use, especially cocaine, continuing to increase among criminals. Additionally, drugs were identified as the most important problem facing the nation in a Gallup poll conducted during the summer of 1989. This paper offers some possible explanations for the divergent trends. Most notably, we suggest that methodological differences in the studies being compared, and lags between trends in the general population and certain subgroups, account for most of the variation in the trend estimates. The paper concludes that illicit drug use is decreasing in the United States. PMID- 1618585 TI - Elderly alcohol misuse. AB - Over 800 patient records were analyzed to identify factors related to problem drinking for older adults. Most importantly, the study found that some symptoms, such as those related to emotional distress, and employment status did have an association with problem drinking for older adults. However, these findings suggest that alcohol use throughout life may simply be carried into old age. Finally, the research noted a distinct pattern of drinking for older females in contrast to that of older males. The reasons for these gender differences, as well as a closer examination on the role of retirement and later onset of drinking for older adults, are identified as topics for future research. PMID- 1618586 TI - Self-efficacy-based smoking situation factors: the effects of contemplating quitting versus relapsing in a Turkish sample. AB - The patterning of smoking situations on the basis of self-efficacy expectations among 174 Turkish smokers was examined by factor analysis which yielded five smoking situations. The examination of the effects of relapse versus contemplation to quit showed that contemplators had higher efficacy expectations as compared to noncontemplators, whereas relapse had no significant effect on efficacy beliefs. Least self-efficacy was observed for situations involving affective elements and highest efficacy for habitual situations. Results were discussed in terms of the heterogeneity of smokers and treatment implications. PMID- 1618587 TI - Conditioned immunopharmacologic effects on cell-mediated immunity. AB - One of the several lines of evidence documenting a relationship between the brain and the immune system is the research on behaviorally induced alterations in immune reactivity. The present review concentrates on the use of immunopharmacologic agents, stress, and antigenic stimuli as unconditioned stimuli (UCSs) in the classically conditioned suppression and enhancement of cell mediated immune reactions including host-vs-graft and graft-vs-host reactions and delayed type hypersensitivity. PMID- 1618588 TI - Thymic endocrinology. AB - Thymus endocrinology is characterized by the action of various hormones on the thymus endocrine milieu consisting of thymocytes, thymic epithelial cells and thymic stromal cells. Extrathymic hormonal influences include pituitary-derived hormones, such as prolactin and indirectly by ACTH via hydrocortisone from the adrenal, by thyroid-stimulating hormone (TSH) via thyroid hormones from the thyroid, and by LH and RH via sex steroids from gonads and adrenal. In addition, the thymus produces several putative thymic hormones: thymosin alpha 1, thymulin and thymopoietin, which have been reported to circulate and to act on both prothymocytes and mature T-cells in the periphery thus maintaining their commitment to the T-cell system and its functions. These endocrine influences decline with age and are associated with "thymic menopause" and cellular immune senescence contributing to the development of diseases in the aged. The intrathymic environment is characterized by a complex network of paracrine and autocrine endocrine signals involving both interleukins and thymic peptides. Thymic epithelial cells respond to IL-1 with proliferation and secretion of IL6 and GM-CSF. They similarly respond to cellular interactions with the production of IL1. Thymic epithelial cells also secrete thymic hormones, as exemplified by the zinc-thymulin complex, under stimulation with IL1 and other hormonal influences. Thymic stromal cells contribute, at minimum, IL1. These various interleukin and thymic hormone influences can be envisioned to operate in a synergistic interactive network to carry the evolving T-cell through its stepwise development to a mature T-cell.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618589 TI - Thymic regulation of the hypothalamic-pituitary-gonadal axis. AB - The thymus gland and the cells that it regulates produce a number of soluble factors that are capable of indirectly modulating the immune system via reproductive neuroendocrine circuits. Studies dating to the turn of the century were designed to evaluate the effects of partially purified thymic extracts in treating various reproductive disorders as well as changes in gonadal tissue weights. More recent studies have focused on the chemical nature of the factors responsible for regulating reproductive function. A number of factors have been described. These include thymosin beta 4 which has been found to stimulate the release of luteinizing hormone releasing hormone and luteinizing hormone (LH). Other factors such as interleukin-1 (IL-1) have been found to inhibit the release of these two peptides. IL-1 has also been found to alter the expression of LH receptors in rat granulosa cells. Certain interferons have been found capable of suppressing estrogen and progesterone release. While many of the studies have been carried out using adult animal models, there is increasing evidence that exposure to cytokines during early development can have long lasting if not permanent effects upon the reproductive axis. These and related topics are the subject of this review. PMID- 1618590 TI - Nutrition and cellular immunity. AB - We have investigated the influence of nutrition on immune function in animals and man over the past two decades. The profound impairment of immune function that had not been observed in children in developing countries could not consistently be reproduced in the laboratory setting; paradoxically, moderate nutritional restriction could even enhance T-cell-based cell-mediated immune responses in experimental animals. Studies of the crucial role of the element zinc in maintenance of vigorous cellular immunity provided at least a partial explanation of this paradox. Zinc, shown to be absolutely crucial for development and expression of both T- and B-cell functions, was commonly deficient as were other micronutrients under many conditions of protein-calorie malnutrition. Indeed, administration of adequate zinc alone could correct some of the T-cell-mediated immune functions in children with protein-calorie malnutrition. In later investigations we found that as long as all essential nutrients were supplied in adequate amounts, 40% chronic energy (calorie) restriction will regularly extend lifespan and maintain vigorous immunologic function while preventing numerous cancers and immunologically based diseases of aging, such as profound and destructive autoimmune diseases in genetically short-lived mice strains, as it was known to do for moderately long-lived rats and long-lived strains of mice. Such undernutrition without malnutrition appears to influence a wide range of critical metabolic and physiologic processes in both short-lived and long-lived animals. One of the most challenging of these influences was a down-regulation of cellular proliferation and cell turnover in each of the rapidly replicating tissues studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618591 TI - Chemicals trophic for the thymus: risk for immunodeficiency and autoimmunity. AB - The thymus is considered as the privileged site of T-lymphocyte generation. The organ is extremely vulnerable to the toxic action of chemicals. The classical example is the "acute stress-induced involution" mediated by glucocorticoid steroid hormones from the adrenal cortex. Nowadays a number of substances have been identified that act in a differential way on the thymus. Examples presented are some organotin compounds acting on immature lymphoblasts in the outer cortex, glucocorticosteroids acting on small thymocytes in the cortex, 2,3,7,8 tetrachlorodibenzo-p-dioxin acting on epithelial cells in the cortex, and cyclosporin acting on dendritic cells and epithelium in the medulla. The mechanisms of toxicity include receptor binding (Ah, aryl hydrocarbon receptor; dioxin); the Ca(2+)-dependent activation of an endogenous endonuclease resulting in DNA fragmentation ("programmed cell death" or apoptosis; dioxin and glucocorticosteroids); and interference with cell proliferation (some organotin compounds). The consequences of toxicity can be a decrease in thymic output of newly-generated T-lymphocytes (i.e. generation of a new T-cell repertoire), or induction of autoimmune symptoms by the creation of unwanted repertoire. This latter phenomenon may be applicable to cyclosporin that under specified conditions can induce so-called syngeneic graft-vs-host disease. This survey presents a brief description of the function of the thymus and the various thymic cell populations involved. Thereafter the susceptibility to toxic insults and the mechanisms of toxicity are reviewed. Finally, the consequences of toxic action for the host defence system, and hence the health status, are considered. PMID- 1618592 TI - Synergy in the toxicity of cytokines: preclinical studies. AB - Synergistic therapeutic activity has been observed both preclinically and clinically with combinations of chemotherapeutic and immunotherapeutic agents as well as with several combinations of immunotherapeutic agents. Frequently the synergistic therapeutic activity has been accompanied by unexpected toxicities demonstrating the need for the development of systematic studies to determine the nature and origin of the toxicity observed when these potent immunoregulatory agents are combined. Several examples have been demonstrated including IFN-gamma and TNF and AZT and IFN-alpha. In this paper approaches to study the pathobiology of combination cytokine therapy and strategies to limit the toxicity, to understand its mechanism, and to retain the synergistic therapeutic activity are discussed. PMID- 1618593 TI - Pre-clinical toxicity of IL-4: a model for studying protein therapeutics. AB - The purpose of this presentation was to review issues and findings in the pre clinical development and evaluation of recombinant human protein therapeutics. Since human cytokines and lymphokines are endogenous proteins, their pre-clinical development and evaluation would seem straightforward and their toxicities minimal. Unfortunately, the pre-clinical development of this class of agents has been problematic and confounding. Some of the clinical toxicities and pharmacodynamics have been predicted by the pre-clinical evaluation and others have not. Some molecules are species specific which limits species selection for pre-clinical evaluation. Other confounding issues include: route of exposure, synergy of toxicity with other lymphokines, length of study design, immunogenicity, predictiveness of pre-clinical evaluation and iatrogenic toxicities. An approach used by SWPRD in the evaluation of this class of molecules was discussed. Insight gained during the pre-clinical and clinical development of these molecules should simplify the further development of protein therapeutics that follow. Specific studies with recombinant human interleukin-4 (rhuIL-4) were reviewed in detail as part of a pre-clinical safety evaluation. Native IL-4 has properties that exemplify many of the immune recognition-induced lymphokines and is produced principally by activated T-lymphocytes CD4+. It is a co-factor in B-cell proliferation and enhances ex vivo B-cell expansion and is believed to be a candidate for the treatment of refractory cancer based on this immune enhancement ability. rhuIL-4 is a 15,400 molecular weight cytokine produced in a yeast expression system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618594 TI - Review: transcriptional and post-transcriptional regulation of interleukin 1 gene expression. AB - Interleukin 1 alpha (IL-1 alpha) and beta (IL-1 beta) are proinflammatory cytokines that are encoded by distinct genes, but share most biological activities. During the past several years, intense investigation has focused on elucidating the molecular basis for the regulation of IL-1 alpha and beta gene expression. While the overall organization of both genes is conserved in mammals, the DNA sequence homology is surprisingly limited. This supports the growing body of evidence suggesting that each gene is regulated by distinct cis- and transacting elements. Most recently, novel regulatory DNA sequence elements and several nuclear regulatory proteins have been identified, which ultimately participate in the control of IL-1 beta gene transcription. In addition to transcriptional controls, the stability of IL-1 mRNA can be selectively regulated by various inducing stimuli and other cytokines. Taken together, these transcriptional and post-transcriptional regulatory mechanisms provide stringent, yet flexible, control over expression of the IL-1 alpha and beta genes. PMID- 1618595 TI - Interleukin 3: from colony-stimulating factor to pluripotent immunoregulatory cytokine. AB - IL-3 is best known as a multicolony-stimulating factor, produced by T-cells, mast cells and eosinophils. Based on its broad spectrum of hemopoietic growth factor activity, the role of IL-3 in the homeostasis of leukocytes is apparent, although the precise mechanisms of this process are yet to be determined. The fact that activated T-helper cells are one of the most potent sources of IL-3 suggests an additional role for IL-3 in the regulation of the immune response. Although the presence of IL-3 receptors on monocytes has been demonstrated, the role of IL-3 in regulating macrophage functions was not clear until recently. We have demonstrated a unique spectrum of macrophage activating properties of IL-3, distinct from that of IFN gamma, IL-4 and other CSFs. These novel macrophage activating properties of IL-3 include its capacity to directly induce the expression of Ia antigens and members of the beta 2 integrin family (e.g. CD11a/CD18[LFA-1]), as well as to contribute to the regulation of cytokine production (IL-1, IL-6 and TNF alpha). Moreover, we observed a significant synergy between IL-3 and IFN gamma in the induction of Ia and LFA-1, as well as between IL-3 and LPS in the induction of Ia and macrophage cytokines. Our data suggest that IL-3 may help control the antigen presentation (AP) capacity of macrophage via the regulation of Ia, beta 2 integrins and macrophage cytokines. It is also possible that the differential state of activation of macrophages that we demonstrated following their induction with IL-3, IFN gamma or IL-3+IFN gamma results in the development of functionally distinct AP cells. Further immunoregulatory properties of IL-3 were observed in vivo by Kimoto and colleagues when IL-3 administration led to profound enhancement of the T-cell dependent immune response, with no changes in the antibody response to T-cell independent antigens. Thus, in vitro and in vivo data both confer an immunoregulatory role for IL-3 in the development of the immune response, most likely via its effects on the antigen presenting cells (macrophages). This review will summarize evidence documenting a range of immunoregulatory properties of IL 3 and discuss the mechanisms of action of IL-3. PMID- 1618597 TI - Transgenic mouse as a tool for the study of autoimmune disease: insulin-dependent diabetes mellitus. AB - Transgenic mice have been used for analyses of cis-acting elements which are involved in the tissue-specific and developmental-specific expression, for analyses of physiological function of genes, or for the production of a human disease model. This approach is especially successful in the fields of immunology and oncology. Several years ago it was shown that the major histocompatibility complex (MHC) class II gene is identical to the immune response gene by demonstrating that the immune response can be restored by the new expression of class II molecules on immunocompetent cells. Recent evidence suggests that the class II molecule is involved in the generation of autoimmune disease, such as insulin-dependent diabetes mellitus (IDDM). The NOD (non-obese diabetic) mouse is shown to be a mouse model for human IDDM. Concerning the class II genes, the NOD mouse has two characteristic features, the lack of I-E and the presence of unique I-A. It is discussed how the role of class II molecules in the development of IDDM in the NOD mouse can be analyzed. In addition, the transgenic technique can be applied to the study of differentiation and oncogenesis of lymphoid cells. Factors or molecules that affect these processes will also be discussed. PMID- 1618596 TI - IL-6 receptor and mechanism of signal transduction. AB - Interleukin-6 (IL-6) is a multifunctional cytokine which acts on a wide variety of cells, exerting growth promotion, growth inhibition, or specific gene expression including cellular differentiation. The IL-6 receptor system consists of two membrane proteins, a ligand-binding chain (IL-6R) and a non-ligand-binding signal transducer, gp130, both of which belong to the cytokine receptor family. Binding of IL-6 to IL-6R triggers the association of IL-6R and gp130, and gp130 in turn transduces the signal. Despite its lack of IL-6 binding property, gp130 is involved in the formation of high-affinity IL-6 binding sites. This two-chain IL-6 receptor system can be applied to some other cytokine receptors, such as IL 3R, IL-5R and GM-CSFR which share a second signal-transducing component. A nuclear factor for controlling IL-6 gene expression (NF-IL6) is a leucine zipper containing transcription factor and is homologous to C/EBP, a liver nuclear factor. NF-IL6 is also involved in the transcriptional regulation of various acute phase protein genes IL-6-triggered association of IL-6R and gp130 on hepatocytes, through intermediate steps including serine-phosphorylation of pre existing NF-IL6 protein, leads to binding of NF-IL6 to IL-6-responsive elements and activation of acute-phase protein genes. PMID- 1618598 TI - The macroscopic and microscopic pharmacology of monoclonal antibodies. AB - When monoclonal antibodies directed against tumor-associated antigens are injected intravenously, they sometimes fail to distribute uniformly in the substance of a tumor. To understand the possible reasons, it is necessary to consider both macroscopic and microscopic features of the pharmacology. We have analyzed antibody penetration into microscopic primary tumors and metastases by melding together information on the global pharmacokinetics, convective and diffusive transport across the blood capillary wall, diffusion through the tumor interstitial space, antigen - antibody interaction, metabolism, and lymphatic outflow. This analysis predicts that the very fact of successful binding will decrease the homogeneity of distribution. We believe that this "binding site barrier" constitutes major challenges to the molecular design of next-generation antibodies and also to the design of many other types of ligands for use in treatment of solid tumors. PMID- 1618599 TI - Levamisole, the story and the lessons. AB - The history of the use of levamisole in man is summarized, from its start as an anthelmintic in the early sixties, through its world-wide recognition as an immunotropic agent especially in the seventies and early eighties, and its return to clinical prominence in 1989-90 as an effective adjuvant treatment for operable colon cancer. The knowledge accumulated from experimental tumour models and from clinical use in various types of cancer, supplemented with the recent evidence obtained from large-scale controlled trials in resectable colon cancer is reviewed. It is speculated that we may not have seen the end of levamisole story yet; also, the role of serendipidity in drug research is emphasized. PMID- 1618600 TI - Review: inducer of cytokines in vivo: overview of field and romurtide experience. AB - We have reported that the bacterial cell-wall skeletons, such as mycobacteria, nocardia, corynebacteria, propionibacteria and listeria, had potent adjuvant activity on immune responses. It was reported that N-acetylmuramyl-L-alanyl-D isoglutamine (MDP) was the minimum structural requirement of adjuvant activity of the bacterial cell-wall skeleton and a variety of MDP derivatives and related compounds were synthesized. Among the synthetic MDP derivatives, we have selected MDP-Lys(L18)(romurtide) as the immunostimulant, by using experimental models for non-specific host resistance against Escherichia coli in mice. Romurtide was shown to have host-stimulating activity against bacterial, fungal and viral infections, cytokine producing activity and the capacity to increase the number of leukocytes and platelets in experimental models. It was also shown that the clinical effectiveness of romurtide on the restoration of the number of leukocytes and platelets of cancer patients treated with chemotherapy or radiation therapy. The mechanism of action of romurtide is discussed. PMID- 1618601 TI - Strategies for the development of new antiarthritic agents. AB - Therapeutic advances in rheumatoid arthritis (RA) have largely focused on the development of non-steroidal antiinflammatory drugs (NSAIDs) with improved characteristics compared with aspirin [Brooks & Day, New Engl. J. Med., 324, 1716 1725 (1991)]. For example, greater potency, safety, improved tolerance in the elderly and reduced frequency of dosing have been achieved. However, these agents are generally considered to be palliative treating of the symptoms of the disease. The development of disease modifying drugs (DMD), also known as second line drugs, for RA has not been very successful. Most of the agents that are currently used in this category were originally used to treat other diseases such as malignancy (cyclophosphamide, methotrexate), Wilson's disease (d penicillamine) and tuberculosis (gold salts) [Pullar, Br. J. clin. Pharmac., 30, 501-510 (1990)]. Unfortunately, none of the agents is ideal and each has potentially serious side-effects. There have been several attempts to develop agents with new mechanisms of action that hopefully will greatly improve these current therapies. PMID- 1618602 TI - The discovery and development of zileuton: an orally active 5-lipoxygenase inhibitor. AB - The enzyme 5-lipoxygenase is a key target in the effort to discover drugs which inhibit the pathophysiology associated with the formation of leukotrienes. The research efforts of these laboratories have focused on the discovery of direct enzyme inhibitors of 5-lipoxygenase. In particular, compounds with hydroxamate or N-hydroxyurea functionalities have proven to be potent inhibitors of leukotriene biosynthesis in vitro and more importantly in vivo. One of these compounds, zileuton (N-(1-benzo-[b]-thien-2-ylethyl)-N-hydroxyurea) has been shown recently to be an effective leukotriene inhibitor in man. The critical approaches and breakthroughs in the discovery and development of zileuton are described. In addition, some recent results with zileuton in animals and man are detailed. PMID- 1618603 TI - Vaccines for control of fertility and hormone dependent cancers. AB - Two vaccines, namely one inducing antibodies against hCG and the other against GnRH, are now in clinical trials. The hCG vaccine has entered Phase II clinical trials in three centres in India after successfully completing Phase I clinical studies in several centres in India and in four countries abroad. The vaccine was found to be devoid of side-effects; its effect was reversible. The available data on 179 cycles indicate that the vaccine prevents pregnancy at antibody titres above 50 ng/ml. A genetically engineered version of the vaccine has also been approved for trials in human lung cancer patients of the type which make hCG. hCG is observed to be a growth factor for such tumours. The GnRH vaccine is usable in both males and females as the deca-peptide is common to both sexes. Following suitable experimental and toxicology studies, the vaccine is currently in Phase I/Phase II clinical trials in patients of prostate carcinoma. Where antibody GnRH antibodies were induced, the LH, FSH and testosterone levels declined. This was accompanied by a reduction in prostate specific antigen. Clinical improvement was observed in many cases. The vaccine has also entered Phase I clinical studies in postpartum women, with the objective to extend the lactational amenorrhoea and extend inter-child interval. PMID- 1618604 TI - European Society for Microcirculation, 17th European Conference. July 5-10, 1992, London, UK. Abstracts. PMID- 1618605 TI - Intracellular actions of vitamin A. AB - Because the effects of vitamin A vary with tissue type and often with the form of vitamin A itself, a complete understanding of the mechanism(s) of action still has not been attained. The action of vitamin A may be at the level of genomic expression, at the membrane level, or both. Intercellular and intracellular transport of vitamin A are facilitated by specific binding proteins but probably not in the cellular uptake of vitamin A. Subcellularly, vitamin A may exert a direct effect on transit through the Golgi apparatus, as observed from both biochemical and morphological studies. In my laboratory, recent work using cell free systems has shown that retinol stimulates transition vesicle formation from endoplasmic reticulum in a GTP-requiring step. PMID- 1618606 TI - Cerebellar lectins. PMID- 1618607 TI - The role of jasmonic acid and related compounds in the regulation of plant development. PMID- 1618608 TI - Subcellular and molecular mechanisms of bile secretion. AB - One of the liver's principal functions is the formation of bile, which is requisite for digestion of fat and elimination of detoxified drugs and metabolites. Bile is a complex fluid made up of water, electrolytes, bile acids, pigments, proteins, lipids, and a multitude of chemical breakdown products. In this review, we have summarized the source of various biliary components, the route by which they end up in bile, including the underlying subcellular and molecular mechanisms, and their contribution to bile formation. One of the reasons why bile formation is so complex is that there are many mechanisms with overlapping substrate specificities, i.e., many biochemically unrelated biliary constituents share common transport mechanisms. Additionally, biliary constituents may reach bile by more than one pathway. Some biliary components are critical for bile formation; others are of minor significance for bile formation but play a major physiological role. The major driving force for bile formation is the uptake and transcellular transport of bile salts by hepatocytes. The energy for bile formation comes from the sodium gradient created by the basolateral Na+/K(+)-ATPase, to which bile salt transport is coupled. The secretory pathway for bile salts involves uptake at the basolateral surface of the hepatocyte, vectorial transcellular movement, and transport across the canalicular membrane into the canalicular lumen. Hydrophilic bile salts are taken up via a sodium-dependent, saturable, carrier-mediated process coupled to the Na+/K(+)-ATPase. This uptake mechanism is also shared by other substrates, such as electroneutral lipids, cyclic oligopeptides, and a wide variety of drugs. Hydrophobic bile acids are taken up by a sodium-independent facilitated carrier mediated mechanism in common with other organic ions, including sulfated bile acids, sulfobromophthalein, bilirubin, glutathione, and glucuronides, or by nonsaturable passive diffusion. Two major carrier proteins have been identified on the hepatocyte basolateral membrane: a 48-kDa protein that appears to be involved with Na(+)-dependent bile salt uptake, and a 54-kDa protein, thought to be associated with Na(+)-independent bile salt uptake. The intracellular transport of bile salts may involve cytosolic carrier proteins, of which several have been identified. Some evidence suggests a vesicular transport mechanism for bile salts. Since bile acids clearly do not enter the cell by endocytosis, formation of transport vesicles must be a more distal event in the transcellular translocation process. Some bile salts appear to be transported within the same unilamellar vesicles that are involved in the secretion of cholesterol and phospholipid.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1618609 TI - Cell biology of the subcommissural organ. PMID- 1618610 TI - [Hemodilution therapy in peripheral arterial occlusive disease]. PMID- 1618611 TI - A different perspective on changing times. PMID- 1618612 TI - PET scanning has promising future at UI Hospitals and Clinics. PMID- 1618613 TI - National health care planning: the shape of things to come. PMID- 1618614 TI - Voiding dysfunction and incontinence. PMID- 1618615 TI - Sexually active teens. PMID- 1618616 TI - Research increasingly aimed at prevention. PMID- 1618617 TI - Medical ethics and health care reform. PMID- 1618618 TI - Internal medicine manpower in Iowa. PMID- 1618619 TI - Internal medicine: concern over supply continues. PMID- 1618620 TI - Peripheral vascular disease. PMID- 1618621 TI - Bacterial meningitis: an 11-year review. PMID- 1618622 TI - More ethical CME. PMID- 1618623 TI - Respiratory distress. PMID- 1618624 TI - Speaks out for BME. PMID- 1618625 TI - A systems model of clinical preventive care: an analysis of factors influencing patient and physician. AB - An ideal model for clinical preventive care must consider the physician, the patient and the many factors which influence each of them. In this paper, we review existing models, examining their strengths and weaknesses. We then propose a new model, the Systems Model of Clinical Preventive Care. This model is unique in its focus on the patient-physician interaction and details the factors impinging on each that promote or inhibit the completion of preventive care activities. These factors include patient and physician predisposing factors, such as health beliefs and attitudes; enabling factors, such as skills and resources; and reinforcing factors, such as social support. Additional factors include health care system organizational factors, such as access or availability; characteristics of the preventive activity, such as cost; and cues to action, such as symptoms or reminders. The proposed model contains components of behavioral, communication, health education and psychosocial theories. We then apply our model to mammography as an example of a screening activity. Finally, we describe the strengths and weaknesses of the proposed model, and identify areas for future research. PMID- 1618626 TI - Evaluation of the Health Belief Model and decision making regarding amniocentesis in women of advanced maternal age. AB - The Health Belief Model (HBM) was developed as an attempt to explain an individual's decision regarding obtaining preventive health care. This model was applied to predict the decisions of women of advanced maternal age regarding their obtaining amniocentesis in a one-year study conducted in Toledo, Ohio. A questionnaire based on the HBM was administered to a sample of 98 pregnant women of advanced maternal age. A total of 96 questionnaires were eligible for inclusion in the study. Sixty-one women reported that they would have amniocentesis, 22 would not, and 13 were unsure. A multivariate analysis of variance among amniocentesis decision groups was performed using the health belief components (perceived susceptibility, perceived seriousness, perceived benefit, perceived barrier) and knowledge as variables. There was a significant difference (Wilks' criterion, p less than .0001) among the three decision groups, but the differences were in the health belief components and not in knowledge. A stepwise discriminant function analysis was used to classify subjects on the amniocentesis decision. Of the variables examined, only the HBM component perceived benefit factor was a significant discriminant (p = .0001). It is not necessarily the lack of knowledge that prevents women who are at risk because of advanced maternal age from having amniocentesis but their perceptions regarding amniocentesis. Genetic counselors need to focus more on exploring the perceptions of amniocentesis benefits in this population to facilitate the decision making process. PMID- 1618627 TI - Self-efficacy for AIDS preventive behaviors among tenth grade students. AB - To guide acquired immunodeficiency syndrome (AIDS) prevention program planning, 181 tenth grade students residing in or near an AIDS epicenter completed a survey measuring past year involvement in sexual intercourse and condom use, beliefs about self-efficacy for AIDS preventive behaviors, and beliefs about susceptibility to and severity of AIDS, and outcome efficacy of AIDS preventive actions. A degree of uncertainty existed for all areas of self-efficacy surveyed: refusing sexual intercourse under a variety of circumstances, questioning sex partners about past risky behaviors, and correct and consistent condom use. Students were most uncertain of their ability to refuse sex with a desirable partner, under pressure, or after drinking alcohol or using marijuana; to purchase condoms, or use them consistently after drinking alcohol or using marijuana; and to question partners about past homosexual history. Those students with lower self-efficacy for refusing sex were twice as likely to have had sexual intercourse. Similarly, those students with lower self-efficacy for correct, consistent condom use were five times less likely to have used condoms consistently. These associations remained even after adjusting for the influence of other AIDS-related beliefs. Implications of these findings focus on exploiting the link between self-efficacy and behavior by building a prevention program that emphasizes skills-building rather than the traditional knowledge-only approach. PMID- 1618628 TI - Health education and injury control: integrating approaches. AB - The prevention of injuries, a major public health problem, is of interest to a growing number of public health professionals from a variety of disciplines. Historically, there has been tension between those who propose injury prevention strategies that focus on the adoption of protective behaviors by individuals and those who propose strategies that circumvent the role of individual behavior by providing automatic or passive protection. This tension may be counterproductive to finding comprehensive solutions to injury problems, and a better understanding of the inherent strengths and limitations of each of these approaches is needed. The purposes of this paper are to: (1) describe the arguments over individual liberties and individual behavior that can occur in the design of injury prevention programs; (2) review the principles that typically guide the development of injury control programs and health education programs; and (3) integrate the two most widely used approaches in injury control and health education programs--Haddon's injury countermeasures and Green's PRECEDE framework -into one program planning framework that addresses both behavioral and nonbehavioral components of an injury problem. This unified framework is offered in the hope that its use will facilitate multidisciplinary, comprehensive approaches to developing injury prevention programs that are efficient and effective. PMID- 1618629 TI - The role of community organizations in AIDS prevention in two Latino communities in New York City. AB - Black and Latino community organizations can play a major role in acquired immunodeficiency syndrome (AIDS) prevention. Their ongoing relationships with their constituents, knowledge of relevant cultural values and channels of communication, and commitment to safeguard the well-being of their neighborhoods are an important resource for AIDS prevention campaigns. In order to better understand the process by which community groups have taken on the issue of AIDS, investigators conducted in-depth interviews with a convenience sample of 47 neighborhood organizations in two primarily Latino communities in New York City. Researchers also attended community meetings, interviewed AIDS educators, and conducted focus groups with respondents. More than half the groups had already sponsored some AIDS prevention activities prior to the first interview. More active groups were more likely to have multiple missions, previous experience with the target population, and prior experience working with people with AIDS. Respondents reported a variety of obstacles to more active involvement in AIDS prevention at the community, organizational, and individual levels. To strengthen the role of community organizations in AIDS prevention, more resources should be provided to grass roots groups, AIDS should be linked to other urgent social problems facing black and Latino communities, and funders and AIDS organizations should respond more flexibly to the needs of neighborhood organizations. PMID- 1618630 TI - Process evaluation of a home-based program to reduce diet-related cancer risk: the "WIN at Home Series". AB - A random mailed survey (response N = 226; 75.3%) of participants in diet-related home-based learning evaluated exposure to recruitment channels and impact on salience, utility, level of participation, sharing the course with others, knowledge, and performing recommended behaviors. A post-only design, the study was conducted in a small Minnesota city (population = 20,000), part of the Cancer and Diet Intervention (CANDI) project. About 18.5% of residents (3,711) enrolled during an 8-week media campaign; women, college graduates, and those over 44 years old were overrepresented. Participants learned about the program through mass media (97%); small media (41.9%); and interpersonal sources (50%). Women were more likely to learn about the course through interpersonal sources. In analysis of variance (ANOVA) modeling, salience and utility predicted level of participation in course activities. Level of participation in turn predicted nutrition knowledge and with salience predicted performance of recommended behaviors. Although the course appealed to individuals who needed it less, there was evidence of diffusion to the unenrolled. About 57% of responding participants reported sharing it with spouses; about 67% reported sharing it with someone outside their households. PMID- 1618631 TI - A Health Belief Model-Social Learning Theory approach to adolescents' fertility control: findings from a controlled field trial. AB - We evaluated an 8- to 12-hour Health Belief Model-Social Learning Theory (HBM SLT)-based sex education program against several community- and school-based interventions in a controlled field experiment. Data on sexual and contraceptive behavior were collected from 1,444 adolescents unselected for gender, race/ethnicity, or virginity status in a pretest-posttest design. Over 60% completed the one-year follow-up. Multivariate analyses were conducted separately for each preintervention virginity status by gender grouping. The results revealed differential program impacts. First, for preintervention virgins, there were no gender or intervention differences in abstinence maintenance over the follow-up year. Second, female preintervention Comparison program virgins used effective contraceptive methods more consistently than those who attended the HBM SLT program (p less than 0.01); among males, the intervention programs were equally effective. Third, both interventions significantly increased contraceptive efficiency for teenagers who were sexually active before attending the programs. For males, the HBM-SLT program led to significantly greater follow up contraceptive efficiency than the Comparison program with preintervention contraceptive efficiency controlled (p less than 0.05); for females, the programs produced equivalent improvement. Implications for program planning and evaluation are discussed. PMID- 1618632 TI - Attitudes, norms, and self-efficacy: a model of adolescents' HIV-related sexual risk behavior. AB - Using data from a cross-sectional, statewide survey of 1,720 Texas ninth graders in 13 school districts, a model of psychosocial predictors of human immunodeficiency virus (HIV)-related sexual risk behavior was tested. Predictor variables in the model, based on variables from the Theory of Reasoned Action and Social Learning Theory, were attitudes, norms, self-efficacy, and behavioral intentions. Attitudes, norms, and self-efficacy predicted 36.4% of the variance in the intention to limit the number of sexual partners and the same variables plus intention predicted 24.6% of the variance in number of sexual partners in the past year. Attitudes, norms, and self-efficacy regarding condom use predicted 17.0% of the variance in condom use intentions; these variables plus intentions predicted 19.0% of the variance in condom use frequency. Attitudes, norms, and intentions were directly related to the number of sexual partners, while self efficacy ad condom use intentions were directly related to frequency of condom use. PMID- 1618633 TI - Histochemical demonstration of glutamate dehydrogenase and phosphate-activated glutaminase activities in semithin sections of the rat retina. AB - The activities of the glutamate metabolizing enzymes phosphate-activated glutaminase (PAG) and glutamate dehydrogenase (Gldh) are demonstrated in semithin sections of the rat retina. Highest activities of both enzymes are found in the photoreceptor inner segments, PAG additionally in the outer plexiform layer and Gldh in the inner plexiform layer and in mueller glial cells. Although their non randomly distribution makes a role in neurotransmitter metabolism possible, their high activities in inner segments point towards the general problem of the functional interpretation of both molecules. PMID- 1618634 TI - Immunocytochemical localization of cathepsin D in the rat osteoclast. AB - We performed immunocytochemical localization of cathepsin D in osteoclasts of the proximal growth plate of the rat femurs using both the avidin-biotin-peroxidase complex method for cryo-semi-thin (1 micron) sections and the colloidal gold labeled IgG method for K4M ultra-thin sections. At the light microscopic level, cathepsin D immunoreactivity in the osteoclasts appeared at the vesicles, granules, and/or small vacuoles. They were distributed throughout the cytoplasm of each cell and were relatively numerous close to the bone surface. This antigen could not be detected at the eroded bone surface. As for other cells, immunoreactivity was seen only in the lysosomes of osteoblast-like cells. Immunoreactivity in the osteoclasts was stronger and greater in the density and number than in osteoblast-like cells. At the electron microscopic level, osteoclasts with well-developed ruffled border possessed numerous cathepsin D containing lysosomes, vacuoles, and coated vesicle-like structures. Cathepsin D containing lysosomes fused with cathepsin-negative vacuoles and formed large secondary lysosomes. Osteoclasts with poorly developed ruffled border possessed fewer cathepsin D-containing lysosomes than those with well-developed ruffled border. No immunogold particles were seen in vacuole-like channel expansions of the ruffled borders, between the channels of the ruffled borders, or on the eroded bone surface. These findings demonstrate that osteoclasts contain a large amount of cathepsin D. They suggest that cathepsin D is necessary for osteoclastic bone resorption, that it plays an indirect rather than direct role. PMID- 1618635 TI - Colocalization of protein kinase C beta-subtype and calcitonin gene-related peptide in rat spinal cord. AB - Colocalization of calcitonin gene-related peptide (CGRP) and protein kinase C beta-subtype (PKC-beta) like immunoreactivities (LI) and the subcellular localization of CGRP-LI were studied in the ventral horn of rat spinal cord. Ultrastructurally CGRP-LI was localized on the membranes of the Golgi-complexes, in multivesicular bodies and in vesicles adjacent to the Golgi-complex in motoneuron perikarya. The colocalization of PKC-beta and CGRP-LI was detected in most of the ventral horn motoneurons. However, few motoneurons were only PKC-beta immunoreactive. These results suggest that PKC-beta may be involved in the regulation of CGRP release from motoric axon terminals. PMID- 1618636 TI - Immunocytochemical localization of phospholipase A2 in hamster spermatozoa. AB - Antibodies raised against porcine pancreatic phospholipase A2 (PLA2) react in immunoblottings with both the antigen as well as with one protein band of about 14 kDa from hamster spermatozoa extracts. Immunoblottings of proteins extracted from spermatozoon head and tail fractions also show similar results. Anti-PLA2 purified IgGs were employed for light and electron microscopic immunocytochemistry in order to detect PLA2 in hamster cauda epididymal spermatozoa. When whole mount spread spermatozoa were used under light (employing the PAP complex) or electron microscopy (using anti-rabbit gold conjugated), the acrosomal area of the gametes shows a noticeable labelling; a characteristic which is not observed in samples treated with the pre-immune serum. Immunocytochemistry undertaken in ultrathin sections from spermatozoon samples embedded in Lowicryl, demonstrates that the antigen appears preferentially distributed in the acrosome. Besides, sperm tails showed a scattered distribution of gold granules in the mitochondria of the midpiece. Results suggest that the antibody used recognizes a PLA2 which is preferentially located in the acrosome and mitochondria. On the other hand, the presence of a surface PLA2 in the plasma membrane covering the acrosome is suggested. This surface PLA2 would be probably related to the acrosome reaction phenomenon that occurs in the spermatozoon before penetrating the oocyte. PMID- 1618637 TI - Islet amyloid polypeptide (IAPP) is synthesized in the islets of Langerhans. Detection of IAPP polypeptide and IAPP mRNA by combined in situ hybridization and immunohistochemistry in rat pancreas. AB - We investigated the localization of IAPP mRNA by means of in situ hybridization in tissue sections of rat pancreas. A 35S-labeled, IAPP-specific DNA probe- hybridized specifically in the islets of Langerhans. This localization was confirmed by immunohistochemical localization of insulin and IAPP polypeptides on adjacent tissue sections. Moreover, combined in situ hybridization of IAPP mRNA and immunohistochemistry of insulin and IAPP polypeptide on the same section, using insulin as specific marker shows the presence of IAPP mRNA in the islets of Langerhans. PMID- 1618638 TI - Distribution of estrogen and progesteron receptors in the uterus: an immunohistochemical study in the immature and adult pseudopregnant rabbit. AB - In order to clarify the distribution and content of estrogen (ER) and progesteron receptors (PR) under changing hormonal influences within the various cell populations of the uterus (glandular and luminal endometrial epithelium, stroma, myometrium), immunohistochemical determinations using specific monoclonal antibodies were made. To correlate the immunohistochemical findings with peripheral hormone levels and specific tasks of the endometrium, 17 beta estradiol and progesterone serum levels were measured and cell proliferation determined by use of BrdU-labelling-immunohistochemistry. At the subcellular level ER and PR were located exclusively in the cell nuclei of female rabbits, which were either immature and lacking any peripheral hormone levels or were pseudopregnant (d0-d8 p.hCG). In the immature rabbits a general faint ER and PR immunostaining was found. In addition to a general increase in ER and PR in all cell populations estrous rabbits (d0 p.hCG) showed a significant rise of ER in the epithelial cells and of PR in the myometrium. Within the epithelial cells and the myometrium the ER dropped heavily within a few days of pseudopregnancy. The PR, however, increased sharply during the first two days of pseudopregnancy and decreased gradually following d4 p.hCG. A close relationship was observed between the high PR content and the proliferation rate of the epithelial cells on d2 p.hCG. In spite of the more rapid decrease of ER compared with PR, the glandular epithelium retained positive immunostaining. In the stroma the ER and especially PR content did not change significantly during the course of pseudopregnancy suggesting that some of the well-known differentiation events in the luminal epithelium may be mediated by the stroma. PMID- 1618639 TI - The influence of buffers during fixation on the appearance of smooth endoplasmic reticulum and glycogen in hepatocytes of normal and glycogen-depleted rats. AB - Liver tissue of normal and glycogen depleted rats was prepared for transmission electron microscopy by perfusion fixation and subsequent osmication in the presence of various buffers, dehydration in aethanol and embedding in epon. The use of Na/K-phosphate or Na-cacodylate to buffer glutaraldehyde led to similar appearance and distribution of SER. When Na-cacodylate was used during osmication, more SER membranes were retained but less accumulations of glycogen were found than after osmication in the presence of Na/K-phosphate. Fixation with s-collidine buffered osmium led to an easily recognisable network of SER comprising wide tubules whereas glycogen was hindered to be stained. Veronal acetate or Na-cacodylate supplemented with sucrose resulted in marked dilation and disintegration of SER. A similar effect was obtained when Na/K-phosphate or Na-cacodylate was used in hyposmolar concentration as buffer for glutaraldehyde. Liver of fasted rats or glucagon-treated rats after perfusion with Na/K-phosphate buffered glutaraldehyde and osmication in the presence of Na/K-phosphate or Na cacodylate comprised glycogen-depleted hepatocytes which contained abundant SER membranes occupying the entire space between other organelles even in samples harvested 3 h after glucagon administration. The diversity in appearance and distribution of SER and glycogen granules, which depends to a large extend on the buffer used, suggests that SER membranes may not be sufficiently stabilized during aldehyde fixation and osmication. We thus consider it likely that large accumulations of glycogen granules are the consequence of disintegration of SER membranes during processing rather than they represent the morphologic substrate of physiological degradation of SER membranes in the course of glycogen synthesis and deposition. PMID- 1618640 TI - Postnatal development and distribution of peptide-containing nerves in the genital system of the male rat. An immunohistochemical study. AB - The distribution and relative density of peptide-containing nerves was studied in the rat in order to assess the progression of neuronal changes during the postnatal development of the male genital system from the prepubertal age to adulthood. Testis, caput and cauda epididymis, ductus deferens, seminal vesicles, prostate and penis from 8-, 20-, 38-, and 70-day-old rats were sectioned and were immunostained with antisera to the neuropeptides calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), and to a general neuronal marker, protein gene product 9.5 (PGP 9.5). The testicular parenchyma and caput epididymis did not show any immunoreactivity. Very scattered CGRP-containing nerves were present in 8-day-old rats; numerous VIP-, CGRP-, and NPY-peptide-containing nerves were observed in the cauda epididymis, ductus deferens, accessory glands and penis of 20-day-old rats. The number of nerves increased in 35-day-old rats while no changes were observed in more adult rats. A parallel increase was seen for the immunostain for PGP 9.5. These data suggest that peptide-containing nerves appear in the genital system after birth and reach a full development before the completion of puberty. Peptide-containing nerves were visible first in the interstitial area and then spread in the muscular coat of the ducts, glands and of the blood vessels. While CGRP- and NPY-containing nerves were distributed in the vicinity of the muscle cells, VIP-containing nerves were also observed in the subepithelial regions, suggesting a possible role of this neuropeptide in the control of epithelial functions. PMID- 1618641 TI - Fluorescent staining of the actin cytoskeleton in human lymphocytes, monocytes and polymorphonuclear cells using a DNAse 1/anti-DNAse 1 immunoglobulin fluorescein conjugated system. AB - The actin associated with membrane-enriched extracts of leukocytes can be quantitated by DNAse 1 inhibition. Using this assay, we previously demonstrated that the actin level in monocytes was significantly higher than that in polymorphonuclear, T and B cells respectively. However, the extracellular location of the actin fraction detected by DNAse 1 inhibition (monomeric "G") remained unclear. This study using the DNAse 1/anti DNAse 1 immunoglobulin fluorescein conjugated system demonstrated that G-actin is present primarily in the cortical cell cytoplasm of leukocytes, in confirmation of our previous biochemical findings. Since the solubilized G-actin activities of membrane-rich lymphoid cell fractions, measured by DNAse 1 inhibition, are a reflection of the migratory potential, this immunofluorescent system may permit identification of the leukocytic cell subpopulations that have a potential for active circulation. PMID- 1618642 TI - A critical evaluation of neoglycoprotein binding sites in vivo and in sections of mouse tissues. AB - Endogenous lectins are reported to play a vital role in cell to cell communication. Their distribution in tissues has been widely studied by the use of labelled neoglycoproteins. In the present study, labelled neoglycoproteins were used on fixed and unfixed tissue sections and the results were compared with those observed after i.v. application of neoglycoproteins in mice. The study indicates that neoglycoprotein binding to tissue sections is not inhibited by application of the simple monosaccharides that were used to synthesize them. Furthermore the binding of neoglycoproteins following i.v. application into mice is rather limited. It is concluded that neoglycoproteins, which are synthesized using simple monosaccharides, do not provide a sensible tool to detect endogenous lectins in animal tissue sections. This is in sharp contrast to the results of most other studies reported in the literature. PMID- 1618643 TI - Immunohistochemical demonstration of glycoconjugates bearing the type 2 chain backbone structure in human fetal, normal and neoplastic gastrointestinal tract. AB - Immunohistochemical distributions of carbohydrate antigens based on the type 2 chain in normal as well as fetal and neoplastic tissues of human gastrointestinal tract were investigated with a monoclonal antibody (MAb) H11 (specific for type 2 chain) alone and in combination with the two MAbs MSG15 (for alpha 2----6 sialylated type 2 chain) and IB9 (for the alpha 2----6 sialylated type 2 chain and glycoproteins having NeuAc alpha 2----6Gal-NAc), and 188C1 (for short- and long-chain Lex antigens) and FH2 (for the long-chain Lex antigen). In the pyloric mucosa of secretors, the type 2 chain is oncodevelopmentally expressed, but in non-secretors it is detected in surface mucous cells of normal gastric mucosa. The alpha 2----6 sialylation, which is confined to endocrine cells of normal pyloric mucosa, occurs in fetal and carcinoma tissues. Irrespective of the secretor status, the short- and the long-chain Lex antigens can be detected in mature and immature glandular mucous cells of normal gastric mucosa, respectively; both antigens are also expressed in fetal and carcinoma tissues. In the colon, the type 2 chain and its alpha 2----6 sialylated counterpart are expressed in an oncodevelopmental manner. The short- and the long-chain Lex antigens are significantly enhanced in colonic carcinoma. The glycoproteins with NeuAc alpha 2----6GalNAc residues appear in gastric and colonic carcinoma as well as intestinalized gastric mucosa and transitional mucosa. Thus, some of these antigens were distinctively expressed in certain epithelial cells lining the normal gastrointestinal tract depending on maturation and patients' secretor status, and some were oncodevelopmental or carcinoma-associated antigens of the human gastrointestinal tract. PMID- 1618644 TI - Altered expression of sialyl-Tn, Lewis antigens and carcinoembryonic antigen between primary and metastatic lesions of uterine cervical cancers. AB - Immunohistochemical examination was performed of serial sections of 24 normal human adult cervical tissues and 53 human cervical carcinomas including 36 cases with lymph node metastasis. For this investigation, monoclonal antibodies directed to Lewis-X, Lewis-Y, sialyl-dimeric Lewis-X (SDLX), sialyl-Tn (STn) and carcinoembryonic antigen (CEA) were used. STn and CEA antigens were expressed very weakly in the normal cervical epithelium but strongly in the cancer cells, indicating the antigens to be oncogenic antigens of cervical squamous cell carcinoma. No significant difference in immunoreactivity was observed between primary and metastatic lesions of carcinoma or between primary lesions with and without metastasis. However, the expression patterns of STn and Lewis-Y antigens were quite different between primary lesions and metastatic lesions. In primary lesions the cancer cell nests tended to be stained centrally, but in metastatic lesions the cancer cell nests tended to be stained peripherally. This finding may reflect an important role of these carbohydrate chains in the process of metastasis of cervical squamous cell carcinoma to regional lymph nodes. PMID- 1618645 TI - Analysis of the transcripts of cytochrome P-450IID gene subfamily in bovine adrenal gland. AB - An in situ hybridization experiment showed that the gene transcripts of P-450IID subfamily were uniformly distributed in bovine liver cells and at low levels in bovine adrenal cortex and medulla. There was no clear localization of transcripts of P-450IID genes in three adrenocortical zones, zona glomerulosa, zona fasciculata and zona reticularis. The intensity of signal obtained in the adrenal cortex and medulla showed approximately 2.5:1 ratio. The presence of gene transcripts of P-450IID subfamily in adrenocortex was confirmed by amplifying cDNA using PCR and hybridizing the PCR products with P-450IID cDNA. PMID- 1618646 TI - Extracellular alkaline phosphatase activity in mineralizing matrices of cartilage and bone: ultrastructural localization using a cerium-based method. AB - The ultrastructural localization of alkaline phosphatase (A1P) activity has been demonstrated in epiphyseal growth cartilage and metaphyseal bone of rats. Epiphyso-metaphyseal specimens were decalcified with EDTA and treated with MgCl2 to regenerate the enzymatic activity before incubation in a medium containing beta-glycerophosphate, MgCl2 and CeCl3. A1P activity was present on the outer surface of the plasmamembrane of maturing and hypertrophic chondrocytes and of osteoblasts. Moreover, the reaction product was present in chondrocyte lacunae, in matrix vesicles, and in cartilage matrix, as well as among uncalcified collagen fibrils of osteoid tissue in bone. The intensity of reaction was the lowest, or completely lacking, where the degree of matrix calcification was the highest. These results suggest that alkaline phosphatase is transported from the cells into the cartilage and bone matrix by its association with matrix vesicles and plasmamembrane components, and that its activity in cartilage and bone matrix is inhibited as it is incorporated in the mineral substance. PMID- 1618647 TI - Labeling with fluorescent carbocyanine dyes of cultured endothelial and smooth muscle cells by growth in dye-containing medium. AB - We describe a method for labeling cultured endothelial cells (ECs) and smooth muscle cells (SMCs) by letting the cells grow for three days in culture medium containing a low concentration of the fluorescent carbocyanine dyes DiI and DiO. We show that good labeling can be obtained with considerably lower concentrations (2.5 micrograms/ml) than has previously been described. With optimal concentration the labeling is very strong and seems to label all membranous structures in the cells. It was possible to clearly distinguish differentially pre-labeled cells both in coculture and seeded on denaturated vascular grafts. The cells remain fluorescent for more than seven days and may be passaged with retained proliferative capability. We suggest that DiI/DiO-labeling using dye containing medium may be used for several cell types and is applicable in tissue culture and in the detection of implanted cells in vivo. PMID- 1618649 TI - Microwave-stimulated glutaraldehyde and osmium tetroxide fixation of plant tissue: ultrastructural preservation in seconds. AB - Microwave-enhanced fixation of animal tissues for electron microscopy has gained in interest in recent years. Attempts to use microwave irradiation for the preparation of plant tissues are rare. In this study; I report on microwave conditions which allow a high quality preservation of plant cell structure. Tissues used were: internodes of Chara vulgaris, leaves of Hordeum vulgare, root tips of Lepidium sativum. Microwave irradiation was done with a commercial microwave oven (Sharp R-5975). Fixatives used were: 2.5% glutaraldehyde in 0.1 M sodium cacodylate buffer, pH 7.2 and 1% osmium tetroxide in veronal/acetate buffer, pH 7.2. Conventional fixations with glutaraldehyde/osmium were compared with microwave fixations. Examinations of thin sections showed that microwave fixation (glutaraldehyde or sequential aldehyde/osmium) is an attractive and rapid alternative method for processing plant tissues for electron microscopy. The optimal conditions found were: microwave oven at power level 50 W, 6.5 ml of fixative solution, irradiation times between 32-34 s, final temperature between 40 degrees C and 47 degrees C. PMID- 1618648 TI - Expression of calbindin-D28k in developing and growing chick testes. AB - Calbindin, a 28-kDa vitamin D-dependent calcium-binding protein was localized immunohistochemically in developing and growing chick testes. The protein first appeared in the germinal epithelium of developing testes of the eight-day-old embryo and remained therein throughout development. Calbindin was not present in the germinal epithelium after hatching. Calbindin was next detected in the spermatogonia and spermatocytes of one-week-old and growing chick testes. Calbindin-positive spermatogonia and spermatocytes gradually increased in number and staining intensity as the seminiferous tubules further developed. A few interstitial Leydig cells were positive for calbindin from five-week-old and older chicks. Comparison of the time-course of appearance and increase in calbindin content in spermatogonia and spermatocytes with spermatogenesis in chickens suggests that calbindin may be involved in the mitotic process in spermatogonia and spermatocytes. PMID- 1618650 TI - Immunocytochemical localization of platelets in baboon hepatic sinusoids using monoclonal mouse anti-human platelet glycoprotein IIIa following induction of thrombocytopenia. AB - A commercially available mouse monoclonal antibody to human platelet glycoprotein IIIa was used to demonstrate sequestration of platelets in hepatic biopsies obtained from baboons following intravenous infusion of echistatin, a novel fibrinogen receptor antagonist derived from the venom of the snake Echis carinatus. Biopsies of liver and spleen were taken prior to administration of echistatin. The hepatic biopsies were either snap-frozen in Freon-22/liquid nitrogen or fixed in 10% neutral buffered formalin. Biopsies of spleen were snap frozen. During infusion of echistatin (2.3 micrograms/kg/min), circulating platelet counts decreased from 331,000/mm3 to 167,000/mm3. Selective sequestration within the liver was confirmed using whole body gamma camera imaging to demonstrate 111Indium-oxine labeled platelet accumulation within the liver during the thrombocytopenic episode. Hepatic biopsies were again taken and either snap-frozen in Freon-22/liquid nitrogen or fixed in 10% neutral buffered formalin. Biopsies of spleen and inguinal lymph node were also snap-frozen. Platelet rich plasma smears, included as positive controls, dewaxed paraffin sections, and cryosections of liver, spleen, and lymph node were stained with monoclonal mouse anti-human platelet glycoprotein IIIa using an avidin biotinylated peroxidase complex (ABC) technique. Prior to infusion of echistatin, platelet staining within the liver was minimal. After echistatin infusion, hepatic cryosections showed prominent platelet staining within hepatic sinusoids. No localization was shown in lymph node, however, the spleen showed prominent platelet staining both before and after echistatin infusion. Platelet rich plasma smears were intensely positive. No prominent platelet staining was observed in formalin-fixed, paraffin-embedded material. Thus, this immunocytochemical technique may help localize platelets in cryosections of tissues from baboons and other primate species. PMID- 1618651 TI - Heterogeneity and distribution of fast myosin heavy chains in some adult vertebrate skeletal muscles. AB - Three monoclonal antibodies, LM5, F2 and F39 raised to chicken fast skeletal muscle myosin, specific for myosin heavy chain (MHC) subunit, were used to study the composition and distribution of this protein in some vertebrate skeletal muscles. These antibodies in immunohistochemical investigations did not react with the majority of the type I fibres in most muscles. Antibodies LM5 and F39 stained all the type II fibres in all the adult chicken skeletal muscles studied. Antibody F2 also stained all the type II fibres in most chicken skeletal muscles tested except in gastrocnemius in which a proportion of both the type IIA and IIB fibres either did not stain or stained only weakly. Antibody F2 unlike LM5 and F39 stained most of the type IIIB fibres in anterior latissimus dorsi (ALD) and IB fibres in red strip of chicken Pectoralis muscle. Antibodies LM5 and F2 in the rat diaphragm reacted with all the type IIA and IIB fibres, while antibody F39 stained only the type IIB fibres darkly with most IIA fibres being either not stained or only weakly stained. In the rat extensor digitorum longus (EDL) and tibialis anterior (TA) muscles, antibody LM5 stained all the IIA and IIB fibres. Antibody F2 in these muscles stained all the type IIA fibres but only a proportion of the IIB fibres. The remaining IIB fibres were either unstained or only weakly positive. Antibody F39 in rat EDL and TA muscles did not only distinguish subgroups of IIB fibres (dark, intermediate and negative or very weak) but also of the IIA fibres. These three antibodies used together therefore detected a great deal of heterogeneity in the myosin heavy chain composition and muscle fibre types of several skeletal muscles. PMID- 1618652 TI - A study on the vibration-dose limit for Japanese workers exposed to hand-arm vibration. AB - To obtain a vibration-dose limit for Japanese workers exposed to hand-arm vibration, the prevalences of vibration-induced white finger (VWF) and numbness of the hand were studied in 5 different groups of workers exposed to segmental vibration. In addition, the prevalence of primary Raynaud's phenomenon (PRP) in the general population without occupational vibration exposure was computed. The vibration levels in the exposed groups (except chain saw operators) ranged from 124.1-129.2 dB (reference value, 10(-6) m/s2). The prevalence of VWF in these groups was 2.2-4.8%. This value was not statistically significant (p greater than 0.05) when compared to the prevalence of PRP in the general Japanese population (2.7-2.9% in our study and 0.5-4.6% in other surveys in Japan). Although the prevalence of numbness of the hands fluctuated among the groups, no significant differences could be demonstrated. Our results were then compared to those of previous reports by literature study [319 papers on hand-arm vibration syndrome (HAVS) and 25 reports on PRP]. At a glance the Japanese population showed a lower prevalence for PRP compared to other countries, which suggested that exposure to cold and biological abilities should also be considered to assess vibration syndrome. A comparison of the vibration characteristics of different tools and the occurrence of VWF in the hands of workers in the literature with those of our data suggested that a daily hand-arm vibration exposure at a level lower than 2.5 m/s2 (128 dB, reference value 10(-6) m/s2) could possibly decrease the risk of VWF among workers exposed to segmental vibration. PMID- 1618653 TI - Acute effects of ozone on EEG activity, sleep-wakefulness and heart rate in rats. AB - Effects of exposure to O3 on EEG activity, sleep-wakefulness and heart rate were examined using conscious rats which had been chronically implanted with electrodes for EEG, EMG and ECG recordings. Exposure to 0.5 ppm O3 for 6 hrs and 1.0 ppm O3 for 3 hrs suppressed amounts of wakefulness (W) and paradoxical sleep (PS) at the expense of an increase in slow-wave sleep (SWS), and lowered the amplitude of fast EEG waves and heart rate (HR). The lowered EEG amplitude and the suppressed PS recovered more rapidly during the post-exposure period than did the lowered HR. The ip administration of atropine sulfate blocked the suppressed W, the increased SWS and the lowered HR, while the lowered EEG amplitude and the suppressed PS were not blocked. These observations suggest that the O3-induced bradycardia results from enhanced activity of cardiac parasympathetic nerves and that the O3-induced changes in W and SWS result secondarily from some circulatory factor including the bradycardia. PMID- 1618654 TI - Health risk appraisal (HRA) and its educational effect on bank employees. PMID- 1618655 TI - Organization of C4 and CYP21 loci in gorilla and orangutan. AB - The standard human haplotype contains two C4 and two CYP21 loci arranged in the order C4A ... CYP21P ... C4B ... CYP21 and intercalated between the class I and class II loci of the HLA complex. The C4A gene is 22 kilobases (kb) long; the C4B gene is either 22 kb or 16 kb long. The CYP21P is a pseudogene characterized by an eight base pair (bp) deletion in exon 3 and other defects; the CYP21 is a functional gene. The standard chimpanzee haplotype is arranged in the same way as the standard human haplotype, except that both C4 genes are of the short variety; like the human gene, the chimpanzee CYP21P gene contains the 8 bp deletion. In the present study we demonstrate that a representative gorilla haplotype also consists of two short C4 genes and two CYP21 genes, neither of which, however, has the characteristic 8 bp deletion. On the other hand, the single characterized orangutan haplotype is organized in the following way: C4A ... CYP21 ... C4A ... CYP21 ... C4B ... CYP21. The first two C4 genes are of the long variety, the third gene is short. None of the defects characterizing the human CYP21P gene is present in any of the three orangutan genes. These conclusions are based on the analysis of overlapping clones isolated from cosmid libraries of the indicated species. The observed haplotype organization of the four primate species can be explained by expansion and contraction of the C4-CYP21 region through unequal homologous crossing-over, which preserves the differentiation of the C4 genes into the A and B categories but otherwise homogenizes these genes, as well as the CYP21 genes, within a given species. The 8 bp deletion in the CYP21P gene is postulated to have occurred before the separation of the lineages that led to modern humans and chimpanzees, but after the separation of these two lineages from the lineage that led to modern gorillas. The 6 kb insertion generating the long C4 gene is postulated to have occurred before the separation of the orangutan, gorilla, chimpanzee, and human lineages. PMID- 1618656 TI - DNA typing for HLA class I alleles: I. Subsets of HLA-A2 and of -A28. AB - A group of HLA-A locus alleles known to be comprised of approximately 14 closely related variants are collectively called HLA-A2 and -A28. Variations among these alleles are given by differences in only a few codons, and in the case of A*6901, elements of A*6801 (exons 1 and 2) and of A*0201 are combined. The purpose of these experiments was to determine the possibility of designing oligonucleotide probes to identify and develop a typing method for all or most of the A2 and A28 variants. Because the regions of interest are also shared by alleles of other groups, allele-specific or group-specific primers were needed to amplify only the alleles under study. HLA-A2-specific amplification of exon 2 and selective amplification of portions of exon 3 of the A2-A28 group were accomplished with sequence-specific primers and after appropriate adjustments of the PCR conditions. Hybridization patterns using products of four PCR reactions with our set of probes distinguished 11 alleles. Two other alleles might be recognized with the reagents used, but were not found in the panels in this study. A*0201 and A*0209, which are different in exon 4, were not resolved because exon 4 was not tested. A new variant of Aw68, defined by a hybridization pattern obtained with our probes, was different from A*6801 only in that it was negative with probe A6. It was called A*68.3. Population studies were performed in North American whites, blacks, and Indians and in a sample of subjects from North China. HLA-A*0201 was the most frequent allele. A*0202 was found only in blacks, and A*0203 and A*0207 were found only in Chinese. Among the A28-positive subjects, Caucasoids were predominantly A*6801 or A*68.3; A*6802 was the most frequent subtype in American blacks; among American Indians the predominant type was A*68.3. The two A28-positive Chinese subjects studied had A*6901. The results obtained demonstrate that DNA typing is an efficient method for determining these alleles. The methodology should be applicable to other class I groups and should be useful for more extensive population studies, for matching for bone marrow transplantation, and for investigation of certain diseases associated with HLA class I alleles. PMID- 1618657 TI - Polymorphism at the HLA-E locus predates most HLA-A and -B polymorphism. AB - The extensive polymorphism of the classic class I antigens has been well described. In contrast, the nonclassic HLA antigens are distinguished by their low polymorphism. We examine here the HLA polymorphism of the HLA-E locus by examining the DNA sequence of cDNA from nine ethnically diverse individuals. From this analysis, we show that there is no polymorphism in the regions including exon 1 and from exon 4 to exon 8, the 3' untranslated exon. In exons 2 and 3, there are two base substitutions, one of which is at a replacement site and the other silent. The replacement substitution changes an arginine to a glycine at position 107, defining two alleles at the HLA-E locus. Using the PCR on exon 3 from genomic DNA and hybridization with oligonucleotide probes, we have examined 90 HLA-typed individuals to determine the relative frequency of the two alleles in the population and their association with the classical antigens. This analysis showed that these two alleles were present at nearly equal frequencies in the population. Surprisingly, both alleles were found in an essentially random association with all but one HLA-A and -B haplotype. The single exception was to the A1-B8 haplotype, which appeared to be linked to only one of the two alleles. One implication of this random association is that these HLA-E alleles may have existed before most of the HLA-A and B polymorphism. Thus, selection has maintained the HLA-E locus essentially unaltered during a time when considerable polymorphism was being selected for at the HLA-A and -B loci. This finding may also have important consequences in an unrelated bone marrow transplant, where it is predicted that 37% of HLA-A and -B matched donors are mismatched at the HLA-E locus. PMID- 1618658 TI - Typing of HLA-DQA1 and DQB1 using DNA single-strand conformation polymorphism. AB - The technique of single-strand conformation polymorphism (SSCP), which is capable of distinguishing DNA sequence variability, was adapted to the identification of the HLA-DQA1 and DQB1 alleles. Eight DQA1 alleles and 12 DQB1 alleles were distinguished by amplifying the second exon of the genes in the presence of radioactive deoxynucleotide, denaturing the products with heat, and separating the single strands by electrophoresis in nondenaturing gels. For DQA1, it was possible to distinguish the eight alleles with standard bis-acrylamide or with a Hydrolink gel matrix. Twelve DQB1 alleles were identified by a protocol employing a combination of oligohybridization and SSCP using products amplified by specific DQB1 primers. PMID- 1618659 TI - Effects of localized HLA class II beta chain polymorphism on binding of antigenic peptide and stimulation of T cells. AB - The relationship between HLA-DR1 polymorphism and recognition of antigen by T cells was investigated. Two allelic variants of HLA-DR1, which differ by amino acid substitution at positions 85 and 86 of the beta chain, were characterized for the effect of substitution on recognition of foreign antigen by DR1 restricted T cells. Substitution of alanine and valine for valine and glycine residues at positions 85 and 86 of the DR1 beta chain resulted in deficient T cell stimulation as demonstrated by the requirement for higher concentrations of antigen to induce maximal levels of T-cell proliferation, induction of lower levels of proliferation at optimal antigen concentrations, and slower kinetics of formation of stimulatory peptide-DR1 complexes. Direct binding studies employing both biotinylated and radioiodinated forms of antigenic peptide demonstrated quantitatively lower levels of peptide bound to substituted DR1 molecules and low levels of site-specific binding as assessed by competitive inhibition analyses. The effect of MHC class II polymorphism on peptide-binding affinity as opposed to induction of appropriate peptide conformation and the impact of polymorphism at DR1 beta chain positions 85 and 86 on allorecognition of HLA-DR1 are discussed. PMID- 1618660 TI - Characterization of a novel DQB1 allele associated with HLA-DQw3: implications for oligotyping. AB - During HLA-DQ oligotyping, the presence of a novel HLA-DQB1 allele was suggested by a pattern of probe hybridization that was inconsistent with the presence of any possible combination of two known alleles. The nucleotide sequence of the second exon of the HLA-DQB1 gene was determined, revealing a novel HLA-DQB1 sequence differing from the DQB1*0301 allele by a single nucleotide substitution at codon 57. All published HLA-DQ oligotyping systems could assign inaccurate oligotypes when this allele is present. An additional amplification primer was utilized to achieve discrimination of all possible combinations of known HLA-DQB1 alleles. PMID- 1618661 TI - The larynx ... so to speak: everything I wanted to know about laryngeal cancer I learned in the last 32 years. PMID- 1618662 TI - Adjuvant chemotherapy for resectable squamous cell carcinomas of the head and neck: report on Intergroup Study 0034. AB - To test the efficacy of sequential chemotherapy as an adjuvant to surgery and postoperative radiotherapy for patients with locally-advanced but operable squamous cell cancers of the head and neck region, a randomized clinical trial was conducted under the auspices of the Head and Neck Intergroup (Radiation Therapy Oncology Group, Southwest Oncology Group, Eastern Oncology Group, Cancer and Leukemia Group B, Northern California Oncology Group, and Southeast Group). Eligible patients had completely resected tumors of the oral cavity, oropharynx, hypopharynx, or larynx. They were then randomized to receive either three cycles of cis-platinum and 5-FU chemotherapy followed by postoperative radiotherapy (CT/RT) or postoperative radiotherapy alone (RT). Patients were categorized as having either "low-risk" or "high-risk" treatment volumes depending on whether the surgical margin was greater than or equal to 5 mm, there was extracapsular nodal extension, and/or there was carcinoma-in-situ at the surgical margins. Radiation doses of 50-54 Gy were given to "low-risk" volumes and 60 Gy were given to "high-risk" volumes. A total of 442 analyzable patients were entered into this study with the mean-time-at-risk being 45.7 months at the time of the present analysis. The 4-year actuarial survival rate was 44% on the RT arm and 48% on the CT/RT arm (p = n.s.). Disease-free survival at 4 years was 38% on the RT arm compared to 46% on the CT/RT arm (p = n.s.). At 4 years the local/regional failure rate was 29% vs. 26% for the RT and CT/RT arms, respectively (p = n.s.). The incidence of first failure in the neck nodes was 10% on the RT arm compared to 5% on the CT/RT arm (p = 0.03 without adjusting for multiple testing) and the overall incidence of distant metastases was 23% on the RT arm compared to 15% on the CT/RT arm (p = 0.03). Treatment related toxicity is discussed in detail, but, in general, the chemotherapy was satisfactorily tolerated and did not affect the ability to deliver the subsequent radiotherapy. Implications for future clinical trials are discussed. PMID- 1618663 TI - Velotonsillar squamous cell carcinoma: 277 cases treated by combined external irradiation and brachytherapy--results according to extension, localization, and dose rate. AB - From 1977 to 1987, 277 patients with velotonsillar cancer (oropharyngeal cancer excluding base of tongue and valleculae) were treated by brachytherapy either alone (14 patients) or combined with external beam irradiation (263 patients) using a new afterloading Iridium-192 technique. The distribution of patients according to the localisation was as follows: 106 tonsillar region, 98 soft palate, 45 anterior pillar, 8 posterior pillar and 20 pharyngoglossal sulcus. According to the UICC TNM classification of 1979, the patients were staged as follows: 65 T1, 103 T2, 101 T3, 8 TX. 172 patients were NO, 74 N1, 3 N2, 20 N3 et 8 NX. According to the tumor extension, the 5 year actuarial local control, locoregional control, specific survival and overall survival by T stage (T1 [65 pts], T2 [103 pts.], T3 [101 pts]) were respectively: local control: 89%, 86%, 69%; locoregional control: 84%, 80%, 67%; specific survival (excluding patients dead with intercurrent disease or second cancer): 78%, 62%, 46%; overall survival: 62%, 53%, 43%. No local recurrence was detected after 3 years. According to the localization, the tumors arising from the tonsillar region, the soft palate and the posterior pillars (A Group) had a better prognosis than the tumors arising from the anterior pillars and glossotonsillar sulcus (B Group). The complications were classified into four grades according to their extension and duration: Grade 1 (minor) with very small tissue ulcer which healed within 2 months with medical treatment (20%). Grade 2 (moderate) (5%), grade 3 (severe) (1.4%), grade 4 (fatal) (0.4%). The dose rate seemed to be relatively higher in patients with grade 2 and 3 complications (70 cGy per hour on average) versus the dose rate of patients without complications (50 cGy per hour) but the difference was not significant. In conclusion, the brachytherapy boost after external irradiation can be performed under favourable conditions with an acceptable rate of complications. It was set out in order to attempt to improve the local control of the tumor while preserving the salivary function and lessening the muscular fibrosis. It shows how experienced the team is, however only a randomized study would allow to state whether this technique brings about a real improvement especially as for tumors T2 or T3. PMID- 1618664 TI - Stage T3 squamous cell carcinoma of the glottic larynx: a comparison of laryngectomy and irradiation. AB - One-hundred eighteen patients with previously untreated T3 squamous cell carcinoma of the glottic larynx were treated with curative intent between March 1965 and November 1988 at the University of Florida. All patients were observed for at least 2 years and 83% were observed for 5 or more years. Fifty-three patients were treated with irradiation alone and 65 patients were treated with surgery alone (32) or combined with irradiation (33). Thirty-two patients treated with irradiation alone had twice-daily fractionation and the remainder had once daily fractionation. The local-regional control rates, including patients successfully salvaged after a local-regional recurrence, were 81% after irradiation alone and 81% after surgery alone or combined with adjuvant irradiation. The local control rates for patients treated with irradiation alone were 53% after once-daily fractionation and 71% after twice-daily fractionation. There was no relationship between vocal cord mobility at 5000 cGy, at the end of radiotherapy, or at 1 month after treatment and subsequent local control. The 5 year cause-specific survival rates were 74% for patients treated with irradiation alone and 63% for patients treated surgically. The incidence of severe complications, including those associated with salvage procedures, was 15% for both treatment groups. The rates of laryngeal voice preservation were 66% after irradiation alone and 2% after surgery. Irradiation alone for selected patients with T3 glottic cancer resulted in similar rates of local-regional control, survival, and severe complications, with a significantly higher likelihood of voice preservation, compared with surgery. PMID- 1618665 TI - Does neck stage influence local control in squamous cell carcinomas of the head and neck? AB - Recently, reports have suggested that the probability of local control of head and neck cancers treated with radiotherapy alone is inversely related to the extent of neck node disease at presentation. This has led some to conclude that primary lesions in patients with neck node metastases should be treated more aggressively than lesions of the same T stage in patients presenting with a clinically negative neck. We reviewed the records of 607 patients with squamous cell carcinoma of the head and neck to determine the relationship between the extent of neck node disease at diagnosis and the probability of tumor control at the primary site. All patients were treated with continuous-course irradiation alone to the primary site and have a minimum follow-up of 2 years. Mucosal sites analyzed included the oropharynx (soft palate, tonsillar region, base of tongue), hypopharynx (pharyngeal wall, pyriform sinus), and supraglottic larynx. Patients with simultaneous primary lesions were excluded from the analysis. Parameters tested included T stage, N stage, and fractionation (once daily or twice daily). For statistical analyses, N stage was grouped as N0, N1, N2A-N3A, and N2B-N3B. Local control was analyzed using a multivariate analysis, the forward stepwise long-rank test of association of covariates. Multivariate analyses revealed that the following parameters significantly influenced local control: oropharynx, T stage only (p = .0010); hypopharynx, T stage (p = .001) and twice-daily fractionation (p = .0031); and supraglottic larynx, T stage only (p = .0002). No significant correlation was found between neck stage and primary tumor control on univariate or multivariate analyses. Our data do not support the conclusion that primary lesions are controlled less often in patients with clinically positive neck nodes. PMID- 1618666 TI - Postoperative radiotherapy in head and neck carcinoma with extracapsular lymph node extension and/or positive resection margins: a comparative study. AB - In head and neck carcinoma, the finding of extracapsular lymph node extension and/or positive resection margins portends poor locoregional control and survival. The effectiveness of postoperative radiotherapy in these patients has been controversial due to insufficient studies comparing resected patients with those also receiving radiation. Between 1982 and 1988, 441 radical head and neck resections were performed at the Medical College of Virginia. Pathologic review of these cases identified 125 with extracapsular lymph node extension and/or positive resection margins. Of these, 43 had extracapsular lymph node extension only, 24 had both positive resection margins and extracapsular lymph node extension, and 58 demonstrated positive resection margins only. Surgery alone was performed in 71 of these patients while 54 cases received surgery and postoperative radiotherapy, (combined modality treatment) CMT. Radiotherapy doses ranged from 50 to 70 Gy. The surgery alone and combined modality treatment groups were comparable with respect to the distribution of positive resection margins and extracapsular lymph node extension. Slightly more CMT patients had clinical T4 disease compared with the surgery alone group (22% vs 14%). Slightly fewer combined modality treatment patients had clinical N0 necks than the surgery alone group (20% vs 29%). Multivariate analysis was performed with the variables T, N stages, radiotherapy, margin status, primary tumor sites, microscopic and macroscopic extracapsular lymph node extension, number of positive lymph nodes, number of nodes with extracapsular lymph node extension. Locoregional control was maintained at 5 years in 59% of the combined modality treatment group and 31% of the surgery alone group (p.0001). Subgroup analysis likewise reveals significant differences favoring the combined modality treatment group for positive resection margins only (49% vs 41%; p = .04), extracapsular lymph node extension only (66% vs 31%; p = .03) and extracapsular lymph node extension+positive resection margins (68% vs 0%; p = .001). Adjusted survival also shows a significant benefit of combined modality treatment vs surgery alone for the entire group (72% vs 41%; p = .001). Multivariate analysis revealed that the use of radiotherapy is a strongly favorable variable for local control and adjusted survival. Macroscopic extracapsular lymph node penetration and positive resection margins are unfavorable independent variables for local control. T-stage is the only variable predicting local control in the combined modality group. Extracapsular extension remains an important negative prognostic variable for survival in both treatment groups. In conclusion, this study demonstrates a locoregional control and survival benefit for postoperative radiotherapy in patients with the high risk pathologic findings of extracapsular lymph node extension and positive resection margins. PMID- 1618667 TI - Cervical nodal metastasis of squamous cell carcinoma of unknown origin: indications for withholding radiation therapy. AB - The records of patients with pathologically confirmed metastatic squamous cell carcinoma involving cervical lymph nodes who were treated at the Mayo Clinic between January 1965 and December 1987 were reviewed. In 117 patients a primary tumor could not be discovered. Of these, 24 patients underwent curative resection of all gross disease by neck dissection or excisional biopsy. All 24 patients presented with unilateral adenopathy. Their median age was 63 years. Eighteen patients were men. Fourteen patients were in clinical stage N1; six, N2a; three, N2b; and one, N3. Six patients had grade 1 or 2 nodal metastases; 14, grade 3; and 4, grade 4. Gross or microscopic evidence of extracapsular tumor extension was noted in eight patients. All patients were followed until death or for a median of 8.5 years (range, 3.3-20.4 years). A squamous cell carcinoma of the upper aerodigestive tract subsequently developed in only one patient (4%) within 5 years of operation. In six patients (25%), a recurrence developed in the dissected neck a median of 3 months (2.4 months-6.6 years) after operation. Five of these patients had extracapsular extension, and four had pathologic Stage N2a or higher neck disease. Both patients with pathologic Stage N1 disease who had recurrences in the dissected neck had extracapsular extension. Delayed, contralateral neck metastases in an undissected neck developed in two patients. The 5-year overall and cause-specific survivals for all 24 patients were 66% and 74%, respectively. Extracapsular extension was a predictor of neck recurrence, control of disease above the clavicles, cause-specific survival, and overall survival. Patients with pathologic Stage N1 neck disease with no extracapsular extension can be managed by surgery alone. Patients with pathologic Stage N2 or higher neck disease or extracapsular extension should be considered for postoperative, adjuvant radiation therapy. PMID- 1618668 TI - Electron beam intraoperative radiation therapy (EBIORT) for localized pancreatic carcinoma. AB - Treatment results for 37 patients with localized pancreatic carcinoma treated using electron beam intraoperative radiation therapy (EBIORT) with curative intent from 1978 to 1990 in National Shikoku Cancer Center Hospital and the related hospitals were presented in comparison with those of a control group comprising 40 patients treated with no use of EBIORT. With additional treatment of EBIORT, 37 patients survived longer than the control 40 patients (p less than 0.05 during the 19th and 31st month). In the macroscopically total or partial resection, patients treated with EBIORT survived slightly longer than the controls. In the unresectable lesions, patients treated with EBIORT survived longer than the control patients (p less than 0.05 during the 7th month). In this group, there was one 5-year survivor who received EBIORT plus postoperative external radiation therapy (ERT) to the unresectable pancreatic head lesion but died 5 years later of massive bleeding from the duodenal ulcerations. Patients with unresectable carcinoma treated by EBIORT plus ERT survived longer than patients treated with EBIORT alone (p = 0.065). Pain relief was obtained in 95.0% of the unresectable patients with pain. Major adverse effects caused by irradiation were gastrointestinal troubles in five patients (leakage of choledochojejunostomy, gastric ulcerations, duodenal stenosis, gastric ulcerations and duodenal stenosis, duodenal perforation and ulcerations). EBIORT proved to be effective in the relief of serious pain and in the improvement of the survival of patients with localized pancreatic carcinoma. PMID- 1618669 TI - Hyperthermia combined with radiation therapy for primarily unresectable and recurrent colorectal cancer. AB - The value of adjuvant hyperthermia to radiotherapy in the treatment of locally advanced colorectal cancers was investigated. Between 1981 and 1989, 71 primarily unresectable or recurrent colorectal tumors were treated with radiotherapy at the Department of Radiology, Kyoto University Hospital. Of the 71 tumors, 35 were treated with radiotherapy plus hyperthermia (group I), while 36 tumors (group II) were unsuitable for hyperthermia mainly because of difficulties with the insertion of temperature probes or the thickness of the patient's subcutaneous fat (greater than 2 cm). The mean total radiation dose was 58 Gy and 57 Gy for groups I and II, respectively. Thirty deep-seated pelvic tumors were treated with an 8 MHz radiofrequency capacitive heating device, and five subsurface tumors were treated with a 430 MHz microwave hyperthermia system. Hyperthermia was given following radiotherapy for 30-60 min for a total of 2-14 sessions (mean 5.7). In 32 of the 35 tumors heated, direct measurement of tumor temperature was performed. For the five tumors treated with the microwave heating device, the means of the mean maximum, average, and minimum measured intratumoral temperatures were 45.4 degrees C, 43.3 degrees C, and 40.6 degrees C, respectively. The corresponding values were 42.2 degrees C, 41.3 degrees C, and 40.3 degrees C for the 27 tumors treated with the capacitive heating device. Effective heating of deep-seated pelvic tumors was more difficult than heating of abdominal wall or perineal tumors. The local control rate at 6 months after the treatment, which was defined as absence of local progression of the tumors, was 59% (17/29) and 37% (11/30) for groups I and II, respectively. The objective tumor response rate (complete regression plus partial response) evaluated by computed tomography was 54% (19/35) in group I, whereas it was 36% (10/28) in group II. A better response rate of 67% was obtained in the 15 tumors with a mean average tumor temperature of greater than 42 degrees C. Although limitation of our current heating devices exist, the combination of hyperthermia with radiotherapy is a promising treatment modality in the treatment of locally advanced colorectal cancer. PMID- 1618670 TI - Radiation therapy for skin cancer near the eye: kilovoltage x-rays versus electrons. AB - When skin cancer near the eye is irradiated, a corneal shield is placed between the lids and globe to protect ocular structures. The effectiveness of the shield was evaluated with 250 kVp x-ray and 6-20 MeV electron beams. To simulate the clinical situation, a face phantom was constructed out of solid pieces of water equivalent epoxy. In the region of the eye the phantom was milled to the exact contour of a human face. The phantom was used to reconstruct the setup that had been used to treat a patient with a 1-cm basal cell carcinoma of the mid portion of the lower lid. A medium-sized corneal shield (2-mm-thick lead plated with 0.1 mm gold) was placed on the eye portion of the phantom. A contoured lead (6 mm thick) face mask was placed on the surface of the phantom to define a 3-cm diameter radiation field that included only the inferior hemisphere of the shield. The doses that the cornea, lens, and retina would receive beneath the midpoint of the inferior hemisphere of the shield were measured using thermoluminescent and film dosimetry. With 6 to 8 MeV electrons, the corneal dose was 2 to 4 times higher than with 250 kVp x-rays. Corneal and lens doses rose rapidly with increasing electron beam energy such that with greater than 8 MeV the shield would provide relatively poor ocular protection. A scanning ion chamber and film dosimetry were used to determine the isodose profiles of 250 kVp x-ray and 6 MeV electron beams for a 3-cm diameter field collimated on the surface. With 250 kVp x-rays the 95% isodose area was 32% wider than with 6 MeV electrons. The ease of shielding and the ability to minimize field size argue in favor of kilovoltage x-rays for early-stage skin cancer near the eye. PMID- 1618671 TI - The use of 3-D dose volume analysis to predict radiation hepatitis. AB - Although it is well known that the tolerance of the liver to external beam irradiation depends on the volume of liver irradiated, few data exist which quantify this dependence. Therefore, a review was carried out of our clinical trial for the treatment of intrahepatic malignancies in which the dose of radiation delivered depended on the volume of normal liver treated. Three dimensional treatment planning using dose-volume histogram analysis of the normal liver was used for all patients. Nine of the 79 patients treated developed clinical radiation hepatitis. None of the patient related variables assessed were associated with radiation hepatitis. All patients who developed radiation hepatitis received whole liver irradiation, as all or part of their treatment, which produced a mean dose greater than or equal to 37 Gy. Dose volume histograms were used to calculate normal tissue complication probabilities based on parameters derived from the literature. The risk of complication was greatly overestimated among patients receiving a high dose of radiation to part of the liver without whole liver treatment. An estimation of model parameters based on the clinical results indicated a larger magnitude for the "volume effect parameter" than the literature estimate (n = 0.69 +/- 0.05 vs 0.32; p less than 0.001). Computation of the normal tissue complication probabilities using the larger value of n produced a good description of the observed risk of radiation hepatitis. These findings suggest that dose volume histogram analysis can be used to quantify the tolerance of the liver to radiation. The predictive value of this parameterization of the normal tissue complication probability model will need to be tested with liver tolerance and dose volume histogram data from an independent clinical trial. PMID- 1618672 TI - Evaluation of multileaf collimator design for a photon beam. AB - Various aspects of multileaf collimator (MLC) design are examined relative to clinical requirements. The characteristics studied included: (a) irregular field edge definition or "effective" penumbra, (b) optimum field coverage for the multileaf portion of the field, and (c) leaf velocity. A film dosimetry technique was developed to measure the rapid 2-dimensional change in dose at an edge defined by a multileaf collimator with the segments staggered. The method applies a correction factor which allows for the changing ratio of scattered to primary photons at the field edge so that the energy dependence of the film is corrected. Stepped lead alloy blocks were irradiated with 6 MV photons to obtain films simulating a double-focused multileaf collimator, and the results were compared to films of fields shaped with standard divergent blocks. The effect of the shape of the leaf face (the end of the leaf) on penumbra was also studied. Proper shaping of the leaf ends may eliminate the need to exactly match beam divergence so that the mechanical of the collimator system is simplified. Leaves having several different end shapes and moving horizontally to intercept a vertical beam were compared to the divergent design where a straight face moves along an arc. The measurements showed that the "effective" penumbra (measured as the distance from the 80 to 20% isodose lines) for the multileaf collimator is a function of the angle between the direction of leaf motion and the edge defined by the leaves. In addition, all leaf end shapes showed some increase in penumbra compared to standard divergent blocking and also had increasing penumbra width as they moved over or back from the field center line. A total of 459 treatment fields and six disease sites were examined to determine the percentage of fields potentially shaped by multileaf segments of specified length. This study showed 93% of the fields had lengths of 30 cm or less and 99% had widths of 25 cm or less. A study conducted to determine the required leaf velocity to shape various target volume configurations during complete rotation (at 1 RPM) showed that a leaf speed of at least 1.5 cm/sec at isocenter is needed for dynamic conformal treatment. PMID- 1618673 TI - Single biopsy, tumor kinetic analyses: a comparison of methods and an extension to shorter sampling intervals. AB - There is emerging and established clinical and laboratory evidence that proliferation of tumor clonogens during radiation therapy can impair local tumor control. The pre-treatment, tumor potential doubling time, T(pot), estimated with in situ bromodeoxyuridine (BrdUrd) labeling, followed by a single biopsy and flow cytometry, may be a predictor of a given tumor's ability to undergo such intra treatment proliferation. Recent studies have found a strong similarity between T(pot)'s determined in this fashion and the effective doubling times of surviving tumor cells during radiotherapy, as estimated from tumor control versus treatment duration data. Furthermore, several preliminary clinical studies have indicated that T(pot) may be a predictor of outcome, with faster tumors doing worse. Accelerated fractionation might overcome such proliferation, but is more acutely toxic and is unlikely to benefit patients with slowly proliferating tumors. Thus, the BrdUrd/single biopsy method may offer the possibility of selecting between accelerated and conventional or hyperfractionated treatment. Several approaches to the analysis of data generated by this method have been described, but there has been little documentation of the validity of methods in experimental systems, particularly in human experimental tumors. This study explores various analytic methods employed with the BrdUrd, delayed, single-biopsy technique used in determining the potential doubling time, T(pot), of tumors. It compares methods of analysis in three experimental systems and in 40 in situ-labeled human tumors, and proposes a method for shortening the required labeling-biopsy interval to a clinically more convenient range of 3 to 4 hours. PMID- 1618674 TI - Morphologic effects of fast neutrons or photons on the canine kidney. AB - Thirty-nine adult male Beagles received either fast neutron or photon irradiation to the right thorax to determine the relative biological effectiveness of fast neutrons on normal pulmonary tissue. The right anterior abdomen, including the cranial half of the right kidney, was included in the field of irradiation. Twenty-four dogs (six/group) received fast neutrons with an average energy of 15 MeV to total doses of 1000, 1500, 2250, or 3375 cGy in four fractions per week for 6 weeks. Fifteen dogs received 3000, 4500, or 6750 cGy of photons (five/group) in an identical fractionation pattern. All 12 neutron irradiated dogs receiving 3375 and 2250 cGy and 1 of 6 receiving 1500 cGy, developed clinical and clinical pathologic signs of hepatic, pancreatic, and gastrointestinal disturbances, but no signs of renal injury were seen. These 13 dogs died or were euthanatized 47-367 days after irradiation. Only 1 of 5 dogs receiving 6750 cGy of photons developed similar signs and died 708 days post irradiation. The remaining 11 neutron irradiated dogs and 14 photon irradiated dogs eventually died of other causes. All 39 dogs were necropsied and their kidneys were compared to each other and to control dogs. Radiation induced lesions included hemorrhages, necrosis and disappearance of tubular epithelia, glomerulosclerosis, atrophy and fibrosis. These lesions were associated with degenerative and occlusive vascular changes and were much more severe in the neutron irradiated dogs. The relative biologic effectiveness of fast neutrons for canine kidney assessed by gross and microscopic pathology is approximately 4.5 (6750/1500). PMID- 1618675 TI - Effect of administration schedules on the potentiation of 1,3-bis(2-chloroethyl) 1-nitrosourea (BCNU) by misonidazole in subcutaneous 9L tumors. AB - Our previous studies demonstrated that metabolism of misonidazole (MISO) by hypoxic cells is required to potentiate the cytotoxicity of 1,3-bis(2 chloroethyl)-1-nitrosourea (BCNU) in sc 9L tumors. To determine the influence of administration schedules on this chemosensitization, tumors were either clamped to produce a reversible hypoxia or left unclamped. MISO (2.5 mmoles kg-1) was administered to rats with unclamped tumors simultaneously with BCNU (9 or 12 mg kg-1), 20 min before BCNU, or 2.5 hr before BCNU, and the drug pharmacokinetics and BCNU cytotoxicity were measured. MISO administered 20 min or 2.5 hr before BCNU increased the plasma elimination half-time (t1/2) of BCNU, but MISO administered simultaneously with BCNU did not change the plasma elimination t1/2 of BCNU. In unclamped sc 9L tumors, all administration schedules decreased the peak BCNU concentration and increased the initial BCNU elimination t1/2; however, the BCNU exposure dose (AUC0-infinity) calculated from these data did not change significantly. In agreement with the AUC calculations, none of the administration schedules altered the BCNU cytotoxicity in unclamped tumors. If the tumors were clamped for 5-120 min after the peak MISO concentration was reached, BCNU-induced cell kill was increased by a constant factor of 3 over the first hour of the clamping period and by an additional factor of 7 over the second hour of the clamping period. If the tumors were clamped for 2 hr after the peak MISO concentration was reached and then BCNU administered 0-60 min after the clamp was released, this chemosensitization remained at a constant factor of approximately 20 for the first 10 min, and then decreased rapidly to a factor of approximately 3 by 20 min after the clamp was released. These data indicate that in sc 9L tumors, (1) at least two biochemical mechanisms are involved in this MISO-BCNU interaction, one of which depends on the duration and extent of the metabolism of MISO by hypoxic cells, and (2) reoxygenation does not immediately eliminate the potentiation of BCNU by MISO. These data also suggest that MISO should be given 2 4 hr before BCNU to achieve the maximum chemosensitization in clinical trials. PMID- 1618676 TI - Late reaction following twice-a-day irradiations in the murine foot: possible repopulation or consequential late effect. AB - The effect of twice-a-day irradiation on the foot reaction was studied in C3Hf/Sed mice. A numerical scoring system was used to evaluate the foot reaction that became visible shortly after irradiation. Peak reaction occurred on the 21st to 23rd day and reappeared after approximately the 200th postirradiation day. These reactions are called early- and late-appearing reactions, respectively. Animals studied for early-appearing reactions were continuously scored for more than 600 days after irradiation. The late-appearing reaction increased continuously or remained constant, but never decreased during the course of the experiments. Animal feet were irradiated with a fraction size from 1.0 to 5.0 Gy twice-a-day daily with a treatment interval of 6 and 18 hours, and varying numbers of fractions were given. A top-up dose of 20 Gy was given as the last dose. The late-appearing foot reaction following a fraction size of 1.5 Gy or greater increased with increasing total dose. However, the increase in the late reaction score with increasing total dose was trivial following multiple doses with a fraction size of 1.0 Gy, suggesting a possible repopulation during prolonged irradiation or that the observed reaction was a consequential late effect. The Fe-plot based on doses which induced fibrosis in one-half of the irradiated animals, showed an alpha/beta ratio of 6.57 +/- 0.62 Gy, and the presence of a breaking point at approximately 1.5 Gy. The alpha/beta ratios calculated by Joiner's method and Thames direct analysis were identical. The slope of the Fe-plot below 1.5 Gy was significantly steeper than that above 1.5 Gy. PMID- 1618677 TI - Design and implementation of a microcomputer-based tutorial in radiation oncology. AB - The design and implementation of a computer-based training system for radiation oncology was undertaken. A frame-based system was chosen, with factual information from Principles and Practices of Radiation Oncology, by Perez and Brady, as the body of knowledge. Each unit of the system was based on a site (chapter) and consists of three sections: text, review questions, and patient management problems. The text section contains text, tables, and references and defines the information upon which the review questions and clinical cases are based. The review questions are multiple choice and true-false, and immediate feedback is given for both correct and incorrect responses. The patient management problems are interactive and provide alternative methods of presenting information and stimulating problem-oriented thought. The emphasis in all sections is on learning rather than testing. Advantages of a computer-based tutorial include the ability to present large volumes of information easily, the capacity for immediate feedback, and the flexibility of format in presentation of material. Potential applications are discussed. PMID- 1618678 TI - Recurrent locally advanced nasopharyngeal carcinoma treated with heavy charged particle irradiation. AB - Between June 1981 and May 1990, 11 patients with recurrent locally advanced nasopharyngeal carcinoma were treated with heavy charged particle radiation at Lawrence Berkeley Laboratory. All patients had previously undergone full course radiotherapy to a median dose of 70.2 Gy [range 61-81 Gy]. Median time to recurrence was 18.2 months. At the time of heavy charged particle radiotherapy treatment, all had evidence of invasion of the base of skull and 7 of 11 had cranial nerve deficits. None of the patients were candidates for brachytherapy because of tumor extent or poor geometry. The tumor histology was squamous cell carcinoma in 10 patients and lymphoepithelioma in one patient. Ten of the 11 patients had received chemotherapy prior to re-irradiation. The heavy charged particle tumor dose delivered ranged from 31.80 GyE to 62.30 GyE (average 50.25 GyE, median 50 GyE). Local control was achieved in 45%. Median survival was 42 months. Actuarial survival was 59% at 3 years and 31% at 5 years (Kaplan-Meier). There were no fatal complications. The results in treating locally advanced recurrent nasopharyngeal carcinoma with heavy charged particles appear superior to those reported by others using photon therapy. PMID- 1618679 TI - Adjuvant chemotherapy for resectable squamous cell carcinoma of the head and neck. Report on Intergroup Study 0034. PMID- 1618680 TI - The uncertainty principle in clinical data. PMID- 1618681 TI - Unknown primary squamous cell carcinoma of the head and neck: is mucosal irradiation necessary? PMID- 1618683 TI - [Answers to various questions on endometriosis]. PMID- 1618685 TI - [Transcervical GIFT--successful treatment of unexplained infertility in Huddinge hospital]. PMID- 1618682 TI - Activation of the heat shock transcription factor by hypoxia in normal and tumor cell lines in vivo and in vitro. AB - Cells exposed to hypoxia increase their synthesis of a specific set of proteins called oxygen regulated proteins. Recently, three of these proteins have been identified as hemoxygenase, Glucose Regulated Protein 78 kilodaltons and Glucose Regulated Protein 94 kilodaltons. In contrast, reoxygenation from hypoxic conditions increases the synthesis of the heat shock proteins. Although the molecular signals required for regulation of both sets of proteins by hypoxia and reoxygenation are still under investigation, it is known that their expression is regulated at the transcriptional level. This finding suggests that these stresses work either singularly or together to control the activation of nuclear transcription factors which bind distinct regulatory sequences in the promoter region of these genes. One possible nuclear transcription factor which could act as a transcriptional regulator for both hypoxia and reoxygenation gene transcription is the heat shock transcription factor. In this report, we focused on the kinetics of HSF activation by hypoxia in normal and tumor cell lines of murine and human origins. In cell culture, both the normal diploid cell line AG1522 and the tumor cell line JSQ-3 possess the same kinetics of HSF activation (binding to the heat shock element) by hypoxia, with maximal induction at or after 3 hr. We have also shown that the activation of HSF occurs in the SCCVII tumor in vivo without clamping, but not in SCCVII cells grown in monolayers. When SCCVII tumors are dissociated and allowed to reoxygenate in cell culture, HSF binding decreased in 5 hr, and was undetectable after 18 hr. Furthermore, one human tumor biopsy tested for the presence of hypoxia by both the pO2 histograph (Eppendorf, Germany) and HSF binding showed good agreement for both techniques. These results suggest that HSF binding may be a useful marker for monitoring the tumor hypoxia. PMID- 1618684 TI - [Glimpses from the history of abortion]. PMID- 1618686 TI - [Baby-friendly hospital in Sweden]. PMID- 1618687 TI - ["Nursing activities"--innovations in a maternal-infant department]. PMID- 1618689 TI - [Report of a study trip to north Germany]. PMID- 1618688 TI - [Ethiopian midwives during the last year]. PMID- 1618690 TI - [Natural family planning]. PMID- 1618691 TI - Cytokines; from phenomenology to molecular biology. PMID- 1618692 TI - Absence of HTLV-II co-infection in HTLV-I-associated myelopathy patients. AB - Syncytium inhibition assay to distinguish between HTLV-I and HTLV-II infection was performed with sera and cerebrospinal fluid of 15 HTLV-I-associated myelopathy (HAM) patients. Also, genome analysis of HTLV-II proviral DNA was performed in some HAM patients by use of the polymerase chain reaction method. All of the HAM patients were negative for co-infection with HTLV-II. PMID- 1618693 TI - Ecologic study of lung cancer risk factors in the U.S. and Japan, with special reference to smoking and diet. AB - Lung cancer mortality rates among United States and Japanese males were compared and related to smoking and dietary data. Mortality rates increased from 1950 to 1985 in both countries, but the absolute values are consistently lower in Japan (38.2 deaths/100,000 in 1985) than in the U.S. (72.2/100,000). The proportion of smokers is higher in Japan than in the U.S. since 1955. Japanese males start smoking considerably later than U.S. males, but smoke a higher quantity of cigarettes per day. Available information on inhalation practices and yield and type of cigarettes smoked showed no differences among the two countries large enough to account for the differences in mortality rates. Further data in this regard should be obtained. Dietary data show that fat consumption (as percentage of calories) is consistently higher in the U.S. than in Japan from 1950 (40% vs. 7.9%) through 1985 (43.5% vs. 24.5%). A linear relationship is observed between lung cancer mortality and fat intake. Our data support the hypothesis that dietary habits may modulate the carcinogenic effects of tobacco smoking. PMID- 1618694 TI - Efficacy of lung cancer screening; comparison of results from a case-control study and a survival analysis. The Japanese Lung Cancer Screening Research Group. AB - A case-control study to evaluate the efficacy of lung cancer screening conducted by us showed that lung cancer screening may reduce the mortality of the disease up to 28%. Assuming this efficacy is unbiased, and that the screening rate is 51.6%, which was observed in the control group in the above study, the number of lung cancer deaths prevented by screening in the study period was calculated to be 47 for males and females combined. In the same study population, screen detected lung cancer patients (N = 207) in the same study period were followed and the 7-year survival rate (46.9%) was compared to the 5-year survival rate (11.3%) obtained by the Osaka Cancer Registry, in which screen-detected lung cancer patients were only 1.8%. The number of lung cancer deaths prevented by screening, estimated by the difference in the above two survival rates, was 74 (95% confidence interval; 55-93). The number of lung cancer deaths prevented by screening estimated from the case-control study was significantly lower than that estimated from the survival analysis. This indicates that the efficacy of lung cancer screening estimated by the case-control study was within the range that could be explained by the actual long-term survivors among the screen-detected patients in the study population. PMID- 1618695 TI - Suppression of diethylnitrosamine-initiated preneoplastic foci development in the rat liver by combined administration of four antioxidants at low doses. AB - Potential synergism between 4 antioxidants acting at low doses on development of glutathione S-transferase placental form (GST-P)-positive liver cell foci was examined in male rats initially given diethylnitrosamine (200 mg/kg, i.p.). Beginning 2 weeks after the initiation, rats received the antioxidants, individually or in combination, in the diet for 6 weeks. All rats were subjected to two-thirds partial hepatectomy at week 3 and killed at week 8. The numbers and areas of GST-P-positive foci were significantly decreased by single treatment with butylated hydroxyanisole (BHA, 1%), tert-butylhydroquinone (TBHQ, 1%) and catechol (0.8%), but not with sesamol (0.5%). Combined treatments (BHA + TBHQ, catechol + sesamol, or all 4 chemicals) at a quarter of the above dose levels resulted in decrease in numbers and areas of foci to levels less than the sums of individual inhibition data obtained with the one-quarter levels. Although these combined effects were not statistically significant in the additive model, the results indicate possible synergistic suppression of carcinogenesis by low-dose combined treatment with anti-cancer agents and the usefulness of the present protocol for this type of analysis. PMID- 1618696 TI - Inhibition of human immunodeficiency virus-1 infection by human conglutinin-like protein: in vitro studies. AB - The lectin-like protein analogous to bovine conglutinin was purified from human serum. The carbohydrate-binding ability of conglutinin-like protein was inhibited by D-mannose, N-acetylglucosamine and L-fucose as well as by mannan-containing oligosaccharides. By applying a lectin-based ELISA system it was demonstrated that conglutinin-like protein binds to human immunodeficiency virus-1 (HIV-1) glycoprotein 120 (gp120) via its carbohydrate binding site. In vitro experiments with T-lymphoblastoid CEM cells revealed that conglutinin-like protein abolishes infection by HIV-1; a 50% cytoprotective concentration of 23.9 micrograms/ml was measured. These findings demonstrate that human conglutinin-like protein binds to HIV-gp120 and inhibits, under the described in vitro conditions, CEM cell infection. PMID- 1618697 TI - Flow cytometric bromodeoxyuridine/DNA analysis of hyperthermia and/or adriamycin for human pancreatic adenocarcinoma cell line Capan-2. AB - The effects of hyperthermia, adriamycin (ADM), and hyperthermia combined with ADM on pancreatic cancer cells were investigated from the viewpoint of cytokinetics using flow cytometric bromodeoxyuridine (BrdUrd)/DNA analysis. Human pancreatic adenocarcinoma cell line Capan-2 was used. The untreated cells could be clearly divided into G1, S, G2M phases on contour plots of BrdUrd/DNA distribution. After heat treatment at 41-43 degrees C, there was an accumulation of cells in the G2M phase which was correlated with the increase in temperature. After heat treatment at 44 or 45 degrees C, there was marked increase in non BrdUrd-labeled cells in the S phase. ADM caused no change in the percent of non BrdUrd-labeled cells in the S phase, even after treatment with a concentration of 1.0 micrograms/ml, though that concentration of ADM caused a marked increase in the percent of cells in the G2M phase. After hyperthermia combined with ADM, the accumulation of the G2M phase increased remarkably, and was significantly higher than that after each treatment alone (P less than 0.005); however, non BrdUrd-labeled cells in the S phase did not increase. In this study the synergistic effect of hyperthermia combined with ADM in increasing the percent of cells in the G2M phase could be observed by flow cytometry. The study illustrates the importance of performing in vitro flow cytometric BrdUrd/DNA analysis of combined therapy prior to the use of the combined therapy in patients. PMID- 1618698 TI - Progression of weakly malignant clone cells derived from rat mammary carcinoma by host cells reactive to plastic plates. AB - Tumor progression is the process by which tumor cells acquire more malignant properties, such as invasiveness and metastasis, during tumor development. To elucidate mechanisms of tumor progression, we examined the role of interactions between the tumor and its host by using a cloned cell line, ER-1, which was derived from a rat mammary carcinoma. ER-1 is weakly tumorigenic and non metastatic when s.c. injected into syngeneic hosts in single cell suspension. However, ER-1 cells show a high incidence of lethal growth when s.c. implanted (5 x 10(2) cells), being attached to a 10 x 5 x 1 mm polystyrene plate. Tumor cell lines (PLT) obtained from tumors which had arisen from the plate-attached ER-1 cells no longer required plates for their growth in normal hosts, and had acquired metastatic ability to the lungs. The malignant phenotypes of PLT were stable under a usual culture condition for at least 6 months. Furthermore, the incidence of tumor development increased when small numbers of ER-1 cells were injected onto plates (or at their periphery) which had previously been implanted s.c. without tumor cells. The tumorigenicity of ER-1 cells increased after they were cocultivated for more than 30 days with host reactive cells obtained from the tissues surrounding the plates. These results suggest that host cells reactive to the foreign body (plastic plate) may not only promote the local growth of ER-1 cells but also convert them into much more malignant tumors. PMID- 1618699 TI - Low frequency of intestinal metaplasia in gastric biopsies from Mexican patients: a comparison with Japanese and Swedish patients. AB - A systematic analysis of the cellular and structural components of intestinal metaplasia (IM) was carried out in 691 consecutive endoscopic gastric biopsies from Mexicans patients. Two-thirds of the patients (461 or 66.7%) had chronic gastritis, 27.6% (or 191 patients) had gastric ulcers and 5.6% (39 patients) gastric carcinomas. IM was found in 17.4% of the gastric biopsies. While IM was present in 27.7% of patients with gastric peptic ulcer, patients with gastric malignancy had only 18.7%, and the lowest rate (13.4%) was found in 461 biopsies from patients with chronic gastritis. IM was influenced by the age but not by the sex of the patients. Only one of 120 biopsies with IM (0.8%) had incomplete IM (a lesion claimed to be a precursor of gastric carcinoma). In a previous study it was found that 32.3% of 359 Swedish patients and 59.2% of 625 Japanese patients with chronic gastritis had IM, the proportion of incomplete IM being 23.3% and 25.1%, respectively. The low frequency of IM among Mexicans (a population with a low incidence of gastric carcinoma), contrasts with the moderate frequency of IM among Swedes (who have a moderate gastric cancer incidence) and with the high frequency of IM among Japanese (with a high incidence of gastric carcinoma). These findings recorded in disparate geographical regions strongly support the view that IM is a lesion evoked by environmental factors and associated with gastric carcinogenesis. PMID- 1618700 TI - Quantitation of gastric intestinal metaplasia by morphometry in Japanese patients. AB - With the aid of an image processor, the length of the intestinal metaplasia (IM) was recorded in 33 gastrectomy specimens (23 with early gastric cancer and 10 with gastric peptic ulcer). A total of 1917 sections were analyzed. The length of the areas with IM and the total length of the muscularis mucosa were measured in individual sections. The resulting ratio (length of IM/length of muscularis mucosa) was noted as the intestinal metaplasia index (IMI), as an expression of the extension of IM in the specimens. The IMI was influenced by the age of the patient and by the histologic type of the tumor: a higher IMI was found among older patients and among patients with adenocarcinoma of intestinal type. A comparison with a similar study done in gastrectomy specimens from Swedish patients indicates that despite the latter group being older, and the tumors being more advanced, the IM was much more extended in the gastric mucosa of the Japanese patients with gastric adenocarcinomas of intestinal type. From the results it is suggested that extended IM in the gastric mucosa may have some bearing on the histogenesis of gastric carcinomas, particularly adenocarcinomas of intestinal type. PMID- 1618701 TI - Suppressive effect of LD78 on the proliferation of human hemopoietic progenitors. AB - LD78 is a cDNA newly isolated from human stimulated tonsillar lymphocytes. The expression of LD78 is related to inflammatory responses and its structure has a homology with macrophage inflammatory protein 1-alpha, which is known to have an inhibitory effect on murine CFU-S. Using a colony assay technique, we examined the effects of LD78 on human hemopoietic progenitors. The addition of doses of 100 ng/ml or more of LD78 suppressed the colony formation of KMT-2, a factor dependent myelomonocytic cell line established from cord blood cells; this suppressive activity was neutralized by the addition of antibody against LD78. The same doses of LD78 suppressed the formation of neutrophil, macrophage, and megakaryocytic colonies which were supported by human interleukin-3 and erythropoietin; however, LD78 did not affect colony formation by either non phagocytic mononuclear cells or sorted CD34+ cells. The conditioned medium of KMT 2 cells or peripheral blood mononuclear cells cultured with LD78 suppressed colony formation by CD34+ cells. From these findings, it is suggested that LD78 affects phagocytic cells and induces factors that are inhibitory for hemopoiesis. We consider LD78 to be a new cytokine that plays an inhibitory role in hemopoiesis. PMID- 1618702 TI - The number of platinum atoms binding to DNA, RNA and protein molecules of HeLa cells treated with cisplatin at its mean lethal concentration. AB - HeLa S-3 cells were treated with 195mPt-radiolabeled cis diamminedichloroplatinum(II) (CDDP) under various conditions, and the relationship between lethal effect and the number of Pt atoms binding to DNA, RNA and proteins was examined. The mean lethal concentrations for the cells treated with CDDP at 37 degrees C for 1, 2 and 3 h were 2.8, 2.0 and 1.1 microgram/ml, respectively. By using identically treated cells, the number of Pt atoms combined with DNA, RNA and protein molecules were determined after fractionation of the cells using the method of Schneider. In this way, the D0 values given as the drug concentration were substituted for the number of Pt atoms combined with each fraction, then the target volumes expressed as the reciprocals of D0 values were calculated for each fraction. The results provide strong support for the idea that DNA is the primary target for cell killing by CDDP, and the target volumes were 5.17 x 10(4), 5.71 x 10(4) and 1.03 x 10(5) nucleotides for 1, 2 and 3 h treated cells, respectively. PMID- 1618703 TI - Kinetic analysis of combination effect of navelbine (KW-2307) with cisplatin against human lung adenocarcinoma PC-12 cells in culture. AB - The combination effect of navelbine (NVB, KW-2307), a newly synthesized vinca alkaloid, and cisplatin (CDDP) was compared with that of vindesine (VDS) and CDDP using human lung adenocarcinoma PC-12 cells. The growth-inhibitory activity of NVB or VDS was time-dependent, whereas that of CDDP was AUC (area under the curve)-dependent. When NVB or VDS was used in combination with CDDP simultaneously for 24 h, antagonism was observed in terms of growth-inhibitory activity. However, additive combination effect was observed when NVB or VDS treatment was followed by CDDP treatment. On this treatment schedule, a synergistic combination effect was observed in terms of the cell-killing activity assessed by colony formation assay. The growth-inhibitory activity of NVB or VDS was detected 24 h after the treatment, whereas that of CDDP became significant 72 h after the treatment. NVB and VDS caused cell accumulation in G2M phase at 10 times their IC80 values, and cells with less than diploid DNA content were detected after 24 h at IC80. CDDP caused accumulation of cells in S phase, and the effect became detectable 16 h after the treatment. The DNA histogram of cells treated with NVB or VDS in combination with CDDP was a superposition of those of cells treated with each drug alone. Significant differences in the characteristics of anticellular activity were not detected between NVB and VDS, although NVB inhibited cell growth at a slightly lower concentration than VDS at the short exposure time of 1-8 h. PMID- 1618704 TI - Metallic elements in the perilymph measured with an inductively-coupled plasma atomic emission spectrometer. AB - Metallic elements in the perilymph of the scala tympani in normal and acoustically overstimulated guinea pigs were measured using a new method, an inductively-coupled plasma atomic emission spectrometry. The concentrations of phosphorus and eight metallic elements, i.e. calcium, copper, iron, potassium, magnesium, sodium, lead and zinc were measured simultaneously in a 2 microliters sample of perilymph. The mean concentration values of calcium, copper, iron, magnesium, phosphorus, lead and zinc were 2.03 mM, 38.5 microM, 69.3 microM, 0.822 mM, 0.851 mM, 43.5 microM and 25.0 microM, respectively. There was no significant effect of acoustic overstimulation on the concentrations of these elements except for magnesium, which decreased significantly after the exposure to a intense sound (2 kHz, 115 dB SPL) for 15 min. This is the first report describing the synchronous determination of metallic poly-elements, including copper, iron, lead and zinc, in the perilymph. PMID- 1618705 TI - Effects of tone burst frequency and intensity on the auditory brainstem response (ABR) from albino and pigmented rats. AB - Young adult male Sprague-Dawley (SD) and Long-Evans (LE) rats were evaluated using the auditory brainstem response (ABR). ABRs were evoked by stimuli with intensities ranging from 15 to 100 dB peSPL. Stimuli were tone bursts of 2000, 4000 and 8000 Hz. As stimulus intensity decreased from 100 to 15 dB, the ABR peak latencies prolonged, interpeak latencies (IPLs) shortened and amplitudes decreased. As stimulus frequency decreased from 8000 to 2000 Hz, ABR latencies prolonged, amplitudes decreased and ABR thresholds increased. The longest IPLs were in response to the 4000 Hz tone bursts. SD rats had ABRs with shorter peak latencies, larger amplitudes and lower thresholds than LE rats. The IPLs usually did not show significant strain-dependent differences. Our observations on stimulus intensity and frequency are consistent with previous reports. Our observations also suggest that the SD (albino) rat has better auditory acuity than the LE (pigmented) rat over the frequency range of 2000 to 8000 Hz. This implies that previous concerns about the use of albino animals in audiological research are somewhat overstated. PMID- 1618706 TI - Single-fibre and whole-nerve responses to clicks as a function of sound intensity in the guinea pig. AB - This paper describes a study of the intensity dependence of click-evoked responses of auditory-nerve fibres in relation to the simultaneously recorded compound action potential (CAP). Condensation and rarefaction clicks were presented to normal hearing guinea pigs over an intensity range of 60 dB. The recorded poststimulus time histograms (PSTHs) were characterized by the latency (tp), amplitude (Ap) and synchronization (Sp) of their dominant peak, parameters that are particularly important for the understanding of the CAP. For all fibres tp decreased monotonically with increasing intensity, in a continuous way for fibres with high characteristic frequency (CF greater than 3 kHz), and in discrete steps of one CF-cycle for low-CF (CF less than or equal to 3 kHz) fibres. An additional analysis of PSTH envelopes revealed that average latency shifts with intensity are similar for all CFs above 2 kHz. For all fibres Ap increased monotonically with intensity; the increase was stronger and maximum values were larger for low-CF than for high-CF fibres. A schematic model PSTH was then formulated on the basis of the experimental data. A sum of these model PSTHs from a hypothesized fibre population was convolved with an elemental unit response (Versnel et al., 1992) in order to simulate the compound action potential. Synthesized CAPs agreed with experimental CAPs in their main aspects. PMID- 1618707 TI - Round-window recorded potential of single-fibre discharge (unit response) in normal and noise-damaged cochleas. AB - Unit responses (URs) of eighth-nerve fibres have been determined at the round window by spike-triggered averaging in both normal and pathological guinea pig cochleas. The pathology was mainly noise-induced damage. The URs have been analysed with respect to their dependence on the fibre's threshold, characteristic frequency (CF) and spontaneous rate (SR). The results from normal cochleas confirmed earlier data (Prijs, 1986): the UR has a diphasic waveform and the amplitude of its negative first peak is about 0.1 microV. From the six parameters (amplitude, latency, and width of the two peaks) by which the UR was described only the amplitude of the positive peak showed a significant variation with CF: a small decrease with increasing CF (CF-range 0.1 to 20 kHz). This finding may possibly be caused by oscillations in the spike-triggered average for low CFs. URs for most low- and medium-SR fibres were found to be large (greater than 0.3 microV). However, this result is interpreted as an artefact caused by synchrony of fibre spontaneous activity. In damaged cochleas only slight changes of the UR were found: the waveform duration became significantly shorter and on some occasions the positive peak increased in amplitude, but latency and amplitude of the negative component of the UR remained unchanged. PMID- 1618708 TI - Cochlear degeneration in aged rats of four strains. AB - Animals with various degrees of inbreeding, some of which are albino, are frequently used in biological research. Albinos do not produce melanin and it is therefore absent from the cochlea. While the function of melanin is unknown, it has been hypothesized that it is involved in cochlear homeostasis. It is possible then, that age-related degeneration may be affected by the presence or absence of melanin. We therefore evaluated young (2-6 months old) and aged (24-36 months old) cochleas in 4 different rat strains: albino Fischer 344 and Lewis rats and pigmented Lewis-Brown Norway F1 rats and Brown Norway rats. Cochlear morphology was the same across all strains of young adult animals with the exception that the pigmented animals had small, darkly stained granules in the stria vascularis. The aged pigmented animals all had large granules as well as small ones. Degeneration of spiral ganglion cells in the apical region of the ganglion had occurred in the old animals of all strains. Strial degeneration at the apex was also present in aged animals. There was no correlation between the presence or absence of melanin and the magnitude of cochlear degenerative changes in the aged animals. The presence or absence of melanin therefore, appears to have no effect on cochlear degeneration in the aged rat cochlea. PMID- 1618709 TI - The human frequency-following response (FFR): normal variability and relation to the click-evoked brainstem response. AB - The frequency-following response (FFR) was recorded from twenty human subjects (11 female and 9 male) over a frequency range of 128-832 Hz in order to study the normal variability of this evoked potential and its dependence on age and sex. Moreover the relation of the FFR to the click-evoked brain stem response (BER) was analyzed in order to contribute to the FFR source discussion. The FFR had a maximum amplitude of about 400 nV and a latency of about 6.4 ms for stimulus frequencies around 350 Hz; the inter-individual variance of the best frequency and of the shape of the frequency function was considerable. Large second harmonics were seen in the FFR to stimuli below about 200 Hz. The FFR amplitude tended to be larger in younger subjects, whereas no such effect was found for the BER. No significant sex effect was found for the FFR amplitude, whereas the BER waves IV and VI were larger for females than for males. There were no correlations between FFR and BER latencies. Significant correlations were found between the amplitudes of the FFR and BER components II, III and IV, but not of waves V and VI. The results support the notion that the FFR and the BER reflect different mechanisms. Moreover the results do not favor the common hypothesis that the inferior colliculus is the major source of the scalp-recorded human FFR, but rather point to lower brainstem levels. PMID- 1618710 TI - Expression of heat shock protein, HSP72, in the guinea pig and rat cochlea after hyperthermia: immunochemical and in situ hybridization analysis. AB - The induction of the heat shock protein, HSP72, was studied in the cochlea of guinea pigs and rats subjected to a hyperthermic stress. Analyses were done by immunoblotting and immunocytochemistry at 6 and 12 h after heat shock, using a commercially available monoclonal antibody (Amersham), and by in situ hybridization 1 h after heat shock using an oligonucleotide probe. In guinea pig immunoblots of the cochlea, HSP72 was present in both unstressed and heat stressed animals and immunocytochemistry did not reveal any difference of staining between them. As opposed to guinea pig, HSP72 was not found in unstressed rat cochlea. Heat shock induced HSP72 expression in most inner ear tissues of the rat examined by immunoblotting. Immunocytochemistry and in situ hybridization localized HSP72 synthesis in ganglion neurons, Schwann cells, spiral limbus, spiral ligament and stria vascularis. The strongest immunoreactivity and highest density of silver grains were seen in the stria vascularis. All blood vessels were strongly immunoreactive and were outlined with silver grains. These results show that HSP72 synthesis can be induced by hyperthermia in rat cochlea and suggest that this protein could be a useful marker for assessment of the effects of specific stresses in this organ. PMID- 1618711 TI - Frequency and intensity discrimination in Mongolian gerbils, African monkeys and humans. AB - Frequency (delta F) and intensity (delta I) difference limens were directly compared in Mongolian gerbils (Meriones unguiculatus), Old World African Monkeys (Cercopithecus mitis, Cercocebus albigena), and humans. Methods employed a repeating background AX discrimination procedure, and positive (food) reinforcement for animals. For delta I, there were small quantitative differences between the species. At 1 kHz, 70 dB SPL, DLs averaged 2.82 dB for gerbils, 2.29 dB for monkeys, and 0.75 dB for humans. For delta F, there were larger differences between the species. At 1 kHz, 60 dB SPL, frequency DLs were highest for gerbils, averaging 108 Hz. DLs were lower for monkeys, averaging 32.6 Hz, similar to recently reported DLs for other Old World monkeys (Prosen et al., 1990). Human DLs, averaging 2.27 Hz, were markedly lower than those of either monkeys or gerbils. These results suggest that animals provide better models of human delta I than delta F. PMID- 1618712 TI - Changes in the tonotopic map of the dorsal cochlear nucleus following induction of cochlear lesions by exposure to intense sound. AB - Hamsters were exposed to intense tones (10 kHz) at levels and durations sufficient to cause stereocilia lesions. The purpose was to determine how the tonotopic map of the dorsal cochlear nucleus (DCN) readjusts to loss of receptor sensitivity. Neural population thresholds and tonotopic organization was mapped over the surface of the DCN in normal unexposed animals and those showing tone induced lesions. The results indicate that cochlear lesions characterized mainly by loss of stereocilia in a restricted portion of the organ of Corti cause changes in a corresponding region of the tonotopic map which reflect primarily changes in the shape and thresholds of neural tuning curves. In many cases the center of the lesion was represented in the DCN as a distinct characteristic frequency (CF) gap in the tonotopic map in which responses were either extremely weak or absent. In almost all cases the map area representing the center of the lesion was bordered by an expanded region of near-constant CF, a feature superficially suggestive of map reorganization. These expanded map areas had abnormal tip thresholds and showed other features suggesting that their CFs had been shifted downward by distortion and deterioration of their original tips. Such changes in neural tuning are similar to those observed by others in the auditory nerve following acoustic trauma, and thus would seem to have a peripheral origin. Thus, it is not necessary to invoke plastic changes in the cochlear nucleus to explain the changes observed in the tonotopic map. PMID- 1618713 TI - Cochleotopic selectivity of a multichannel scala tympani electrode array using the 2-deoxyglucose technique. AB - The 2-deoxyglucose (2-DG) technique was used to study the cochleotopic selectivity of a multichannel scala tympani electrode array in four cats with another acting as an unstimulated control. Each animal was unilaterally deafened and a multichannel electrode array inserted 6 mm into the scala tympani. Thresholds to electrical stimulation were determined by recording electrically evoked auditory brainstem responses (EABRs). Each animal was injected with 2-DG, and electrically stimulated using bipolar electrodes located either distal or proximal to the round window. The contralateral ear was stimulated with acoustic tone pips at frequencies that matched the electrode place. Stimulation of both distal and proximal bipolar electrodes at 3 x EABR threshold, evoked localized 2 DG labelling in both ipsilateral cochlear nucleus (CN) and the contralateral inferior colliculus (IC), which was very similar in orientation and breadth to labelling evoked by the contralateral tone pips. The cochleotopic position of labelling to proximal stimulation was located in the 24-26 kHz region of each structure, whereas the distal labelling was located around 12 kHz. Distal stimulation at 10 x EABR threshold produced very broad 2-DG labelling in IC centered around the 12 kHz place. The present 2-DG results clearly illustrate cochleotopic selectivity using multichannel bipolar scala tympani electrodes. The extent of this selectivity is dependent on electrical stimulus levels. The 2-DG technique has great potential in evaluating the efficacy of new electrode array designs. PMID- 1618714 TI - Stiffness of hair bundles in the chick cochlea. AB - The stiffness of hair bundles from isolated chick cochlear hair cells was measured in tissue culture medium. A water jet was used to deflect fiberglass fibers, quartz fibers, and hair bundles of isolated hair cells. A voltage displacement curve was generated for a water jet ramp stimulus applied to miniature fiberglass and quartz fibers. Fiber displacements were measured using video image subtraction techniques. A force-voltage calibration curve was then derived for the fibers by modelling them as cantilever beams subjected to point forces at the tips. A voltage-displacement curve was then generated for isolated hair cell stereociliary bundles using the same procedure as for the fibers. A corresponding force-displacement curve was derived for isolated hair cells under water jet stimulation by correlating maximum ramp voltage from the hair cell's voltage-displacement curve to a corresponding force applied to a fiber from the fiberglass fiber calibration curve. The stiffness of the hair bundle, which is the slope of the hair cell's force-displacement curve, was then calculated using Hooke's law, assuming the force was distributed along the entire length of the hair bundle. The mean stiffness value was 5.04 +/- 2.68 x 10(-4) N/m for 14 hair cells, and was in close agreement with previously reported stiffness values of several investigators utilizing different animal models and procedures. PMID- 1618715 TI - Conjugal transfer of R plasmids to and from Enterobacteriaceae isolated from sewage. AB - The potential of the transfer of natural plasmids between sewage strains has been studied. In vitro transfer was conducted at 37 degrees C in tryptone soya broth and sterile raw sewage as mating media. In situ transfer was carried out in sterile raw sewage within membrane diffusion chambers at 10.6 degrees C. When the recipient was a laboratory strain of Escherichia coli K-12, the in situ frequency values were significantly lower (P less than 0.001) than those obtained in vitro for the same mating pair. When the laboratory recipient was replaced with recipients from the same sewage source, frequency values decreased progressively from the optimum conditions to the most adverse. However, in situ frequency values were higher than those for the same donors mated with a laboratory recipient. PMID- 1618716 TI - Synthetic DNA probes for detection of genes for enterotoxins A, B, C, D, E and for TSST-1 in staphylococcal strains. AB - A dot blot hybridization technique with oligonucleotide probes was developed for the specific detection of the TSST-1 gene and the staphylococcal enterotoxin (SE) genes A, B, C, D and E. For each toxin gene a probe sequence was chosen from the previously determined sequence. A total of 145 staphylococcal strains (133 Staphylococcus aureus and 12 coagulase-negative staphylococci (CNS) were studied by this genotypic method and by two phenotypic assays (gel immunodiffusion and ELISA). An excellent correlation (96%) was observed between the genotypic and phenotypic assays. DNA from two CNS strains hybridized with a probe without detection of the corresponding toxin (SEB for one strain and SEC for the other strain). One Staph. aureus strain was shown to be an SEC producer, but was not detected by the corresponding probe. Gene probe and immunological assays seem to be complementary methods for studies of staphylococcal strains producing (or potentially producing) TSST-1 or enterotoxins. PMID- 1618717 TI - Detection of salmonellas by DNA hybridization with a fluorescent alkaline phosphatase substrate. AB - This study evaluates a DNA hybridization assay for salmonella with AttoPhos (JBL Scientific, San Luis Obispo, CA), a fluorescent substrate for alkaline phosphatase. The probe used (50 ng/ml) was a biotinylated 600 bp fragment consisting of a tandem repeat of an insertion sequence (IS200) found in most Salmonella spp. evaluated. The hybridization was carried out at 65 degrees C for 2 h without prior prehybridization and hybrids were detected by the addition of a streptavidin-alkaline phosphatase conjugate. Circles (5 mm) were cut from the membrane and placed in a cuvette containing 1 ml of 1 mmol/l AttoPhos. The reaction was evaluated after 30 min at 37 degrees C with a fluorometer with an excitation wavelength of 440 nm and an emission wavelength of 550 nm. The sensitivity of the probe was estimated to be 10,000 copies of target DNA or 5 x 10(-20) mol of DNA. All 74 salmonella strains tested reacted with the probe but none of the 98 heterologous species tested gave positive results. The results of this study indicate that our assay method, which employs a biotinylated tandem repeat of IS200 and AttoPhos, is a specific and highly sensitive quantitative method for the detection of salmonellas. PMID- 1618718 TI - Fungal and actinomycete spore aerosols measured at different humidities with an aerodynamic particle sizer. AB - An aerodynamic particle sizer (APS) that uses laser Doppler velocimetry was used to determine aerodynamic diameters of spores of fungal and thermophilic actinomycete species common in mouldy hay, aerosolized at different humidities and temperatures. Results were compared with those obtained from inertial impaction in a cascade impactor. The APS gave slightly smaller measurements than the cascade impactor. Both methods gave aerodynamic diameters generally slightly smaller than the average spore dimensions observed on cascade impactor slides with a microscope. The latter measurements were less than axial dimensions given in the literature. Brief passage of spores through air at 95% relative humidity (RH) and 38 degrees C, compared with 40% RH and 20 degrees C, caused an immediate increase in their aerodynamic diameter and the breaking of chains of spores. Cultures maintained at 75% RH and aerosolized at 98% RH similarly produced larger spore particles than those passed through dry air. These findings have implications for mould-induced asthma and allergic alveolitis since they relate to physical behaviour of airborne spores and particle deposition sites in the lung. PMID- 1618719 TI - The effect of dilution rate and pH on biomass and proteinase production by Micrococcus sedentarius grown in continuous culture. AB - Micrococcus sedentarius, an organism associated with pitted keratolysis, produced two proteinases in culture supernatant fluids, as shown by non-denaturing PAGE with overlaying with a casein substrate. A mixture had optimal activity at pH 10 with azocasein substrate. At pH 7.1 and 8.1 in continuous culture with varying dilution rates high proteinase production occurred at relative specific growth rates (mu rels) 0.39 and 0.77 and biomass concentrations decreased with increasing dilution rate. One proteinase was constitutive and varied little in production with different growth rates. The other proteinase was under control with high production at low growth rates and no production at high growth rates. With varying pH at mu rels 0.39 and 0.77 maximum biomass concentration and proteinase production occurred between pH 8.0 and 9.0 as did the highest specific growth rate. These results support the hypothesis that Mic. sedentarius produces pitting in the stratum corneum when the skin is hydrated and the pH rises above neutrality. PMID- 1618720 TI - Typing of Aeromonas strains from patients with diarrhoea and from drinking water. AB - Aeromonas strains (187) from human diarrhoeal stools and from drinking water (263) in The Netherlands were typed by three different methods. Biotyping alone was found to be of little value for epidemiological studies because 84% of all strains belonged to only 10 biotypes. Common biotypes could be further differentiated by serotyping. Gas-liquid chromatography of cell wall fatty acid methyl esters (FAME) was useful for species identification as well as for typing: 86% of all strains could be identified to the species level, and within this group 92% of all identifications corresponded with the biotype. Cluster analysis and principal component analysis of FAME profiles could be used for comparison of strains from different sources and gave the same general conclusions as bio- and serotyping. There was little overall similarity between Aeromonas strains from human (diarrhoeal) faeces and from drinking water, differences being most pronounced for Aeromonas caviae and least for A. sobria. PMID- 1618721 TI - An unusual low-abdominal tumor: cystadenoma of the seminal vesicle. AB - Cystadenoma of the seminal vesicle is an extremely rare benign tumor, which to our findings has only been mentioned earlier in seven previous reports. It is a benign and mostly multilocular tumor, thought to originate from embryologic remnants. Preoperative diagnosis is rarely made. Complete extirpation is the correct treatment. We present this first Belgian case with a discussion of imaging techniques, symptomatology, pathology, diagnosis, and treatment. PMID- 1618722 TI - Acutely symptomatic benign mediastinal cysts. AB - Usually, cystic mediastinal masses are considered as benign. However, the size of the cyst is of importance, chiefly in a closed space such as the superior mediastinum. Rarely a dramatic symptomatology may develop though this was the case in the two patients we describe, who were admitted in the department. In the first case (a parathyroid cyst), the symptoms were due to a thrombosis of the left innominate vein, and in the second case (a thyroid cyst), the severity was dominated by a dramatic compression of the trachea and the vessels. The contribution of computed tomography is nowadays undisputed. It enables the diagnosis of the cystic nature before surgery. The diagnosis can easily be confirmed by percutaneous drainage. PMID- 1618723 TI - [Lumbar arachnoid cysts: 2 unusual cases]. AB - Two cases of arachnoid cyst in the lumbar region are described. One is intradural, acquired, and associated to severe arachnoiditis while the other is extradural in location and probably congenital. The interest of myelography, CT myelography, and MRI for the diagnosis is discussed. PMID- 1618724 TI - [Encysted gossypiboma of the lesser omentum: complementary aspects of echography and computerized tomography]. AB - The authors report the fortuitous demonstration of an asymptomatic gossypiboma during the preoperative staging of a rectal carcinoma 13 years after abdominal surgery for perforated gastric ulcer. Ultrasonography disclosed a well-defined hypoechoic mass containing highly echogenic foci with a strong posterior shadow. The CT findings are reported, as well as the complementary aspects of sonography. Differential diagnosis from tumors of the lesser omentum is also presented. PMID- 1618725 TI - Osteoarthritis of the facet joints and its role in low-back pain: evaluation with conventional tomography. AB - Thirty-seven patients with chronic low-back pain and an atypical irradiation to one or both legs were examined by conventional tomography of the facet joints. A disc herniation was excluded by computed tomography (CT) in 31 patients. The facet joints were considered normal in 4 patients. Four grades of facet joint disease were used to classify the pathological changes. Correlation of the radiological findings with the facet joint block by injection of a local anesthetic was obtained in 12 patients. It appears that conventional tomography is a very sensitive technique as it is possible to detect even discrete abnormalities of the facet joints. However, as it is time consuming and high in radiation dose, the examinations should be reserved for patients with a normal CT examination of the lumbar spine in whom there still remains a high suspicion of facet joint disease. PMID- 1618726 TI - [Vertebral osteoporosis manifesting systemic mastocytosis]. AB - A case of systemic mastocytosis in a 33-year-old man, with multiple spine fractures caused by severe osteoporosis, is presented. The diagnosis could only be established three years after the initial symptoms, when the patient developed skin eruption. Skin and bone biopsy, as well as histamine dosage, confirmed the diagnosis. PMID- 1618727 TI - Magnetic resonance imaging of extraabdominal desmoid tumors. AB - The authors describe the MR appearance of extra-abdominal desmoid in three patients, with longitudinal follow-up during a period of up to 29 months in two of them. For the MR examinations various pulse sequences, including spin-echo and gradient-echo sequences, were used. Both non-enhanced and Gd-DTPA contrast enhanced studies were made. We found gradient-echo T2*-weighted sequences best suited for the detection of extra-abdominal desmoids. Best correlation between MR features and histologic findings was obtained on spin-echo T2- and contrast enhanced T1-weighted studies. Although preliminary, our results suggest that MRI might predict evolution of extra-abdominal desmoids by providing data about cellularity and relative amount of mucoid matrix of the lesions. PMID- 1618728 TI - [Anorectal anaplastic cancer (neuroendocrine)]. AB - An extensive case of undifferentiated neuroendocrine carcinoma with small cells of the anorectal region is reported. The carcinoma is related to pulmonary anaplasia and quite rare in the colonic and rectal region. Its aggressivity is considerable with a strong propensity for hematogenous and lymphatic metastases and with a disastrous prognosis: 0% survival over 1 year. The incidence, the characteristic features, the histogenesis, and the anatomical pathology of this rare neoplasm are mentioned. Furthermore, the case illustrates a radiological pattern typical for major lymphatic dissemination with an intra- and extraparietal component. The mechanism of dissemination is explained by the "lymphatic block" theory. The absolute necessity of obtaining an histology in radiologically unusual and/or extensive cases is mentioned. PMID- 1618729 TI - Signal transduction and osmoregulation in Escherichia coli: a novel mutant of the positive regulator, OmpR, that functions in a phosphorylation-independent manner. AB - In Escherichia coli, expression of the outer membrane proteins, OmpF and OmpC, is regulated by the regulatory factors, EnvZ and OmpR, at the transcriptional level in response to the medium osmolarity. In this particular osmotic regulation, phosphorylation of OmpR at an aspartate residue (Asp-55) by EnvZ plays an important role. The previously isolated mutant, ompR55Q, with the amino acid replacement of Asp-55 to Gln, exhibits an OmpF- and OmpC- phenotype. In this study, we isolated a novel type of ompR mutant, in which the defect caused by the ompR55Q mutation is suppressed. The intragenic suppressor mutation we isolated results in the amino acid replacement of Tyr-102 to Cys in the N-terminal domain of OmpR, and exhibits an OmpF+ and OmpC+ phenotype in response to the medium osmolarity in an EnvZ-independent manner. It was revealed that this amino acid replacement in OmpR enhances the in vitro DNA-binding ability to the cognate DNAs. These results suggested that OmpR is capable of functioning in a phosphorylation-independent manner under certain in vivo conditions, and further suggested that an EnvZ-independent mechanism may also be involved in the osmotically regulated expression of ompF and ompC. PMID- 1618730 TI - Mutualism based on stress: selective synthesis and phosphorylation of a stress protein by an intracellular symbiont. AB - The effects of a temperature shift-up and various metabolic inhibitors on the protein synthesis of an endosymbiont isolated from the pea aphid were studied. The syntheses of at least three major polypeptides were stimulated transiently immediately after a temperature shift-up, and treatment with ethanol and heavy metals (Cd2+ and As2+). One of these proteins, the 63 kDa heat-shock protein (63 kDa HSP), was immunoprecipitated with antiserum raised against symbionin, which is selectively synthesized by the endosymbiont harbored by the aphid bacteriocytes. The 63 kDa heat-shock protein has a molecular mass of 800 kDa and is more acidic than symbionin. It was also shown that symbionin is subject to phosphorylation in vivo and in vitro after a temperature shift-up. It was thought likely that forms of environmental stress such as heat shock and metabolic inhibitors stimulate the synthesis of a phosphorylated form of symbionin. It was also suggested that the in vitro phosphorylation of symbionin is due to its own catalytic activity. Since symbionin is a homolog of the Escherichia coli groEL protein, a stress protein, it is likely that the endosymbiont suffers stress when harbored by the bacteriocytes and responds in a similar manner to environmental stress when outside these cells. PMID- 1618731 TI - Carbohydrate-binding peptides from several anti-H(O) lectins. AB - Peptide fragments have been obtained from L-fucose-binding anti-H(O) lectins [Lotus tetragonolobus lectin (LTA) and Ulex europeus lectin I (UEA-I)] and di-N acetylchitobiose-binding anti-H(O) lectins [Ulex europeus lectin II (UEA-II) and Laburnum alpinum lectin I (LAA-I)] by treatment with endoproteinase Asp-N or Lys C. The peptide fragments were fractionated by affinity chromatography on a column of Fuc-Gel for LTA and UEA-I, and on a column of N-acetyl-D-glucosamine oligomer Sepharose for UEA-II and LAA-I. The peptides with affinity for these columns were identified by peptide sequencing. All of these retarded peptides were found to be parts of the metal-binding regions of these lectins. It is strongly suggested that these peptides represent the carbohydrate-binding and metal ion-binding sites of legume lectins, respectively. PMID- 1618732 TI - Effect of dietary sodium restriction on mRNA for aldosterone synthase cytochrome P-450 in rat adrenals. AB - Changes in the level of mRNA for aldosterone synthase cytochrome P-450 (cytochrome P-450aldo) in rats on dietary sodium restriction were studied by means of Northern and slot blot hybridization using an oligonucleotide probe that allowed differentiation of the message for this enzyme from that for cytochrome P 450(11)beta. These two enzymes have been shown to be highly homologous with each other, exhibiting 88% homology in their nucleotide sequences in the coding region. Upon sodium restriction for 2 weeks, cytochrome P-450aldo mRNA in rat adrenals increased 7-fold, whereas the cytochrome P-450(11) beta mRNA level in the same adrenals did not change significantly. The increase in cytochrome P 450aldo mRNA paralleled that in cytochrome P-450aldo protein, as analyzed by immunoblot technique. These results, together with our previous finding that angiotensin II induced cytochrome P-450aldo in rat adrenocortex [Shibata, H., Ogishima, T., Mitani, F., Suzuki, H., Murakami, M., Saruta, T., & Ishimura, Y. (1991) Endocrinology 128, 2534-2539], suggest that the production of cytochrome P 450aldo is regulated by angiotensin II at the pretranslational level, most likely at the transcriptional level. PMID- 1618733 TI - Membrane assembly of lactose permease of Escherichia coli. AB - Lactose permease, the lacY gene product in Escherichia coli, is an integral membrane protein. Its induction was examined in secAts and secYts mutants by measuring o-nitrophenyl-beta-galactoside uptake activity. In contrast to the synthesis of the maltose binding protein, the malE gene product, which is dependent on the secA and secY gene products, lactose permease seemed to be produced and integrated functionally into membrane independently of SecA or SecY. Gene fusion of the lamB signal sequence to the N-terminal part of the lactose permease gene resulted in production of active fused permease in the E. coli membrane. The signal sequence did not seem to be processed, judging from its mobility on SDS polyacrylamide gel electrophoresis. E. coli cell growth was super sensitive to induction of production of the fused permease with the signal sequence in contrast to induction of the normal lactose permease. These results are consistent with the above observation that production and integration of LacY protein into membrane is relatively independent of the SecY protein that may have a certain specificity for the signal sequence or, more generally, membrane translocation intermediates. PMID- 1618734 TI - Characterization of adrenodoxin precursor expressed in Escherichia coli. AB - The precursor of bovine adrenodoxin (pAd), a mitochondrial protein, was expressed in Escherichia coli. The cloned cDNA of pAd was ligated to an expression vector pET-3d, and silent mutations were introduced into the N-terminal portion of the cDNA in order to increase the expression. The precursor was highly expressed (approximately 20% of the total cell protein) as the inclusion body, and contained an iron-sulfur center as judged from its optical absorption spectra. The inclusion body was solubilized with 7 M urea and pAd was purified in the presence of urea. The purified pAd was efficiently imported into isolated bovine adrenal cortex mitochondria and processed to the mature form. The import reaction required ATP inside the mitochondria in addition to the inner membrane potential, and was strongly inhibited by trypsin treatment of the mitochondria, as in the case of the in vitro translated precursor. It was, however, not dependent on the unfolding activity of the cytosolic factor with extramitochondrial ATP. PMID- 1618735 TI - Reconstitution of the active form from the amino- and carboxyl-terminal fragments of a reactive site-modified subtilisin inhibitor of adzuki beans (Vigna angularis). AB - The complex of an adzuki bean subtilisin inhibitor (ASI-II) with its target enzyme, prepared at pH 7.6, was subjected to reversed-phase HPLC in a trifluoroacetic acid-acetonitrile system. Two peptide fragments derived from the reactive site-modified ASI-II were obtained. The analyses of the amino acid composition and sequence of these two fragments revealed that one corresponded to the region from the amino-terminal Lys to the reactive site P1 Ala and the other, to the region from the reactive site P1' Asp to the carboxyl-terminal Gly of the inhibitor. Although neither fragment alone showed inhibitory activity against subtilisin, an equimolar mixture of both fragments was found to inhibit strongly the target enzyme, as did the intact inhibitor. Thus, it was suggested that the two fragments have strong specific affinity with each other, regenerating the reactive site-modified ASI-II, to inhibit the target enzyme. PMID- 1618736 TI - Evidence for the existence of O-linked sugar chains consisting of glucose and xylose in bovine thrombospondin. AB - We have recently discovered unusual sugar chains [xylose-glucose and (xylose)2 glucose] linked to a serine residue in the first epidermal growth factor (EGF) like domains of human and bovine coagulation factors VII, IX, and protein Z. The sequence surrounding this serine residue has a common -Cys-X-Ser-X-Pro-Cys- structure. Since one (residues 533-538) of the three EGF-like domains found in human thrombospondin contains the conserved sequence, we examined the presence of such O-linked sugar chains in bovine thrombospondin (bTSP) and its 210-kDa fragment. Component sugar analysis after pyridylamination (PA) of the acid hydrolysates of the S-aminoethylated proteins revealed that the proteins contain glucose (Glc) and xylose (Xyl). The oligosaccharide moieties released from intact bTSP by hydrazinolysis followed by pyridylamination were separated into two PA oligosaccharides by high performance liquid chromatography (HPLC). Component sugar analysis of these PA-oligosaccharides indicated that they consist of Glc and Xyl in molar ratios of 1:1 and 1:2 (or 1:3). The reducing ends of both PA sugar chains were found to be PA-Glc, as judged from the retention time of the HPLC peak of their hydrolysates. The presence of these PA-sugar chains in bTSP was confirmed by HPLC mapping with two different columns, using standard PA-di- or PA-trisaccharide derived from coagulation factors. From these results, we concluded that bTSP contains O-linked sugar chains consisting of Glc and Xyl in one of its three EGF-like domains. PMID- 1618737 TI - Purification and characterization of formaldehyde dehydrogenase from rat liver cytosol. AB - Formaldehyde dehydrogenase was purified to electrophoretic and column chromatographic homogeneity from rat liver cytosolic fraction by a procedure which includes ammonium sulfate precipitation, DEAE-cellulose-, hydroxyapatite-, Mono Q-chromatography, and gel filtration. Its molecular mass was estimated to be 41 kDa by gel filtration and SDS-PAGE, suggesting that it is a monomer. It utilized neither methylglyoxal nor aldehydes except formaldehyde as a substrate. It has been reported that liver class III alcohol dehydrogenase and formaldehyde dehydrogenase are the same enzyme and oxidize formaldehyde and long chain primary alcohols. However, the enzyme examined here did not use n-octanoi as a substrate. The Km values for formaldehyde and NAD+ were 5.09 and 2.34 microM at 25 degrees C, respectively. The amino acid sequences of 10 peptides obtained from the purified enzyme after digestion with either V8 protease or lysyl endopeptidase were determined. From these results, the enzyme was proved to be different from the previously described mammalian formaldehyde dehydrogenase and is the first true formaldehyde dehydrogenase to be isolated from a mammalian source. PMID- 1618738 TI - Effects of low culture temperature on the induction of hsp70 mRNA and the accumulation of hsp70 and hsp105 in mouse FM3A cells. AB - We have shown that heat shock does not induce the synthesis of hsp70 in FM3A cells maintained at a low culture temperature of 33 degrees C although it does so in cells maintained at 37 degrees C [T. Hatayama et al. (1991) Biochem. Int. 24, 467-474]. In this paper, we show that FM3A cells maintained at 37 degrees C produced hsp70 mRNA during continuous heating at 42 degrees C or during postincubation at either 37 or 33 degrees C after being heated at 45 degrees C for 15 min, whereas cells maintained at 33 degrees C did not produce hsp70 mRNA during continuous heating at 37, 39, 42, or 45 degrees C, or during postincubation after being heated at any temperature. Thus the lack of hsp70 synthesis in cells maintained at 33 degrees C seemed to be due to the absence of hsp70 mRNA induction. Also, hsp70 was accumulated in cells maintained at 37 degrees C during continuous heating at 42 degrees C and during postincubation at 37 degrees C after heat shock at 45 degrees C, but not during postincubation at 33 degrees C. The cellular level of the constitutive hsp73 as well as the mRNA level were both similar in cells maintained at 33 and 37 degrees C. On the other hand, the cellular level of the constitutive hsp105 in cells maintained at 33 degrees C was only half of that in cells maintained at 37 degrees C. These hsp105 levels increased significantly in both types of cells after continuous heating at 39 degrees C. These findings indicate that the culture temperature affects not only the induction of hsp70 mRNA but also the accumulation of hsp70 and hsp105 in the cells. PMID- 1618739 TI - Isolation and characterization of a mouse protein C cDNA. AB - Protein C (PC) is a vitamin K-dependent serine protease, a deficiency of which results in thrombus. There is no spontaneously occurring mouse model of the disease. Attempts to create such a model in mice by using anti-sense gene technology requires isolation of a normal mouse PC cDNA. When a mouse liver (BALB/c) cDNA library was screened using a human PC cDNA as a probe, nine overlapping cDNA clones were isolated and sequenced. The cloned mouse PC cDNA comprised 1,512 nucleotides and the open reading frame of the cDNA encoded a polypeptide of 461 amino acids residues including a leader peptide composed of 41 amino acids. Mouse PC exhibited high homology to both human and bovine PCs. Mouse PC also had several structural features common in other PCs; locations of 23 Cys residues, location of putative beta-hydroxy Asp71, possible carbohydrate attachment sites involving Asp residues at amino acid positions 249, 314, and 330, and location of active sites such as His212, Asp258, and Ser361. Northern blot hybridization analysis identified a single species of mouse PC mRNA (2.0 kb in length) in mouse liver. PMID- 1618740 TI - Comparison of two reconstituted systems for in vitro transcription and replication of influenza virus. AB - The transcription and replication of influenza RNA can be studied in vitro by the reconstitution of functional ribonucleoprotein (RNP) complex from viral core proteins including the RNA polymerase (complex of three P protein subunits) and nucleoprotein (NP), and model templates. Here, two different core protein preparations, one based on CsCl centrifugation (CS enzyme) and the other on micrococcal nuclease treatment of viral cores (MN enzyme), were compared side-by side. Short model RNA templates and their 3'-half molecules of both viral RNA (vRNA) and complementary RNA (cRNA) senses were reconstituted with the core protein preparations in parallel, and RNA polymerase activity was tested either in the presence or absence of ApG or globin mRNA as primers. Both enzyme preparations were active in the syntheses of short vRNA and cRNA transcripts using ApG as a primer, although the synthesis of cRNA was 2-10-fold higher (depending on the template used) than the synthesis of vRNA. The MN enzyme, however, was more active per weight of total protein than the CS enzyme, probably because of its higher content of RNA polymerase. Both enzymes failed to show primer-independent synthesis of vRNA. The differences observed in the synthesis of short transcripts using globin mRNA as a primer are discussed. PMID- 1618741 TI - Nonspecific lipid transfer protein in castor bean cotyledon cells: subcellular localization and a possible role in lipid metabolism. AB - The subcellular localization and several biochemical activities of nonspecific lipid transfer protein (nsLTP) were investigated. A section of a castor bean cotyledon cell was labeled with anti-nsLTP serum followed by protein A-gold. Gold particles were more abundant in the glyoxysome matrix and the vessel cell wall than in other areas. Cell fractionation analysis of 6-day-old castor bean cotyledons by sucrose density gradient centrifugation demonstrated that 13% of nsLTP was distributed in the glyoxysomal fraction, identified on the basis of catalase as a marker, and 87% in the soluble fraction near the top of the gradient. The location of castor bean nsLTP in glyoxysomes was further confirmed by in vitro import experiments. The synthesized precursor of nsLTP (pro-nsLTP-C) was incorporated into intact castor bean glyoxysomes and processed to the mature form after import into the glyoxysomes, but it was not imported into canine pancreatic microsomes. Castor bean nsLTP-A was found to possess the ability to bind oleic acid and oleoyl-CoA by means of a method involving Lipidex 1000. The dissociation constants (Kd) for oleic acid and oleoyl-CoA binding to nsLTP-A were 4.8 and 5.0 microM, respectively. The saturated binding capacities (Bmax) for oleic acid and oleoyl-CoA per mol of nsLTP-A were 1.1 and 1.2 mol, respectively. When acyl-CoA oxidase activity was assayed in the glyoxysomal fraction, marked enhancement of the activity was observed in the presence of nsLTP. These results suggest the possibility that nsLTP regulates fatty acid beta-oxidation through the enhancement of acyl-CoA oxidase activity in glyoxysomes. The occurrence of castor bean nsLTP in the vessel wall was discussed. PMID- 1618742 TI - Trypsin treatment may impair the interfacial activation action of lipoprotein lipase. AB - Lipoprotein lipase was expressed in Chinese hamster ovary (CHO) cells transfected with human lipoprotein lipase cDNA. The lipoprotein lipase retained tributyrin, water-soluble substrate, hydrolyzing activity (esterase activity). The catalytic action of this enzyme was studied by monitoring the esterase activity. The esterase activity was enhanced 4.5-fold by the addition of triolein emulsified with Triton X-100. This process was named interfacial activation. Treatment of LPL with trypsin (100 micrograms/ml, 37 degrees C for 10 min) caused the loss of the triolein hydrolyzing activity without that of the esterase activity. The esterase activity of trypsin-treated LPL was not enhanced by the addition of the triolein emulsion. The trypsin-treated LPL retained the ability to bind to very low density lipoproteins (VLDL). These results are consistent with the idea that LPL has a catalytic site and a lipid interface recognition site, and that the enzyme undergoes interfacial activation, in which the concealed catalytic site is revealed after the enzyme binds to the surface. Based on this hypothesis, the results obtained suggest that trypsin nicking may impair the interfacial activation process and cause the loss of the lipase activity. PMID- 1618743 TI - Primary structure and disulfide bridge location of arrowhead double-headed proteinase inhibitors. AB - Two arrowhead proteinase inhibitors (inhibitors A and B) were characterized and their primary structures were determined. Both inhibitors A and B are double headed and multifunctional protease inhibitors. Inhibitor A inhibits an equimolar amount of trypsin and chymotrypsin simultaneously and weakly inhibits kallikrein. Inhibitor B inhibits two molecules of trypsin simultaneously and inhibits kallikrein more strongly than does inhibitor A. The amino acid sequences of inhibitors A and B were determined by sequencing the reduced and S carboxamidomethylated proteins and their peptides produced by cyanogen bromide or proteolytic lysylendopeptidase or Staphylococcus aureus V8 protease cleavage. Inhibitors A and B consist of 150 amino acid residues with three disulfide bonds (Cys 43-Cys 89, Cys 110-Cys 119, and Cys 112-Cys 115) and share 90% sequence identity, with 13 different residues. Since the primary structures are totally different from those of all other serine protease inhibitors so far known, these inhibitors might be classified into a new protease inhibitor family. PMID- 1618744 TI - Ligation activity of FLP recombinase. The strand ligation activity of a site specific recombinase using an activated DNA substrate. AB - The FLP protein of the 2-microns plasmid of yeast belongs to the integrase family of site-specific recombinases whose members form a covalent bond between a conserved tyrosine of the recombinase and the 3'-phosphoryl group at the site of cleavage. We have made an activated DNA substrate and have shown that FLP can promote efficient strand ligation without forming a covalent intermediate with the DNA substrate. The strand ligation activity of FLP is independent of its ability to cleave DNA. Since site-specific recombinases are members of the larger class of topoisomerases, these findings may be generally applicable to other members of this class of enzymes. PMID- 1618745 TI - Altered cellular interactions between endothelial cells and nonenzymatically glucosylated laminin/type IV collagen. AB - Laminin and type IV collagen are two major basement membrane glycoproteins. In previous studies it has been shown that nonenzymatic glucosylation induces structural alterations of these macromolecules and also reduces their ability to self-associate. In the present study, endothelial cells were tested for their ability to adhere and spread on nonenzymatically glucosylated laminin and type IV collagen. Adhesion and spreading were reduced when glucosylated macromolecules were used as substrates. Glucosylation-induced changes in adhesion and spreading may be an important initial event signaling other phenotypic modifications of cells in the microvasculature and may be a crucial factor in order to understand the pathogenesis of diabetic microangiopathy at the molecular level. PMID- 1618746 TI - Post-transcriptional regulation of expression of plasminogen activator inhibitor type 1 mRNA by insulin and insulin-like growth factor 1. AB - In humans and non-human primates, alternative cleavage and polyadenylation of plasminogen activator inhibitor type-1 (PAI-1) pre-mRNA transcripts results in two forms of mature mRNA, an unstable 3.2-kilobase (kb) form, and a relatively more stable 2.2-kb form. Insulin and insulin-like growth factor I (IGF-1) increase steady state levels of PAI-1 mRNA in Hep G2 cells independently and synergistically. In the present study we found that the rate of transcription of the PAI-1 gene is not affected by insulin, IGF-1, or both but that insulin prolongs the half-life of the 3.2-kb PAI-1 mRNA species 2.7-fold without affecting the half-life of the 2.2-kb species. In contrast IGF-1, alone or with insulin, markedly prolongs the half-lives of both species. Our results demonstrate a novel mechanism of regulation of expression of the PAI-1 gene by insulin and IGF-1 operating at the post-transcriptional level. PMID- 1618747 TI - Activation of insulin receptor signaling by a single amino acid substitution in the transmembrane domain. AB - The insulin receptor is a ligand-activated tyrosine kinase composed of two alpha and two beta subunits. A single transmembrane domain composed of 23 hydrophobic residues is contained in each beta subunit. We examined the role of the transmembrane domain in regulating insulin receptor signaling by inserting a negatively charged amino acid (Asp) for Val938 (V938D). Chinese hamster ovary (CHO) cells were stably transfected with a plasmid containing both the neomycin resistance gene and either the wild-type or the mutant (V938D) insulin receptor cDNA. Insulin binding increased similarly in CHO cells stably transfected with the wild-type and the V938D-mutant insulin receptor cDNA. Insulin stimulated glucose transport and cell growth in cells expressing the normal insulin receptor. By contrast, in the absence of insulin, glucose transport and cell growth in CHO-V938D cells were as high as in insulin-stimulated control cells and no longer responsive to insulin stimulation. Phosphorylation of the beta subunit of the insulin receptor was also increased in CHO-V938D cells not exposed to insulin. These results support an essential role of the transmembrane domain of the insulin receptor in the transduction of insulin signaling. PMID- 1618748 TI - The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds and internalizes Pseudomonas exotoxin A. AB - The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2 MR/LRP) is a large cell-surface glycoprotein consisting of a 515 kDa and an 85-kDa polypeptide; this receptor is thought to be responsible for the binding and endocytosis of activated alpha 2-macroglobulin and apoE-enriched beta very low density lipoprotein. A similar high molecular weight glycoprotein has been identified as a potential receptor for Pseudomonas exotoxin A (PE). We demonstrate that the alpha 2 MR/LRP and the PE-binding glycoprotein have a similar mobility upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis and are immunologically indistinguishable. Furthermore, affinity-purified alpha 2 MR/LRP binds specifically to PE but not to a mutant toxin defective in its ability to bind cells. The 39-kDa receptor-associated protein, which blocks binding of ligands to alpha 2 MR/LRP, also prevents binding and subsequent toxicity of PE for mouse fibroblasts. The concentration of receptor-associated protein that was required to reduce binding and toxicity to 50% was approximately 14 nM, a value virtually identical to the KD measured for the interaction of receptor-associated protein with the purified receptor. Overall, the studies strongly suggest that the alpha 2 MR/LRP is responsible for internalizing PE. PMID- 1618749 TI - The A20 zinc finger protein protects cells from tumor necrosis factor cytotoxicity. AB - Resistance against the cytotoxic actions of tumor necrosis factor alpha (TNF) is an active process requiring the synthesis of TNF-inducible proteins. The specific TNF-induced proteins so far identified (manganese superoxide dismutase and plasminogen activator inhibitor type 2) as having a role in resistance against TNF cytotoxicity are able to confer only partial protection to cells, suggesting that other genes are involved. A20 is a TNF-induced primary response gene which encodes a novel zinc finger protein. In this report we demonstrate that A20 protein is induced by TNF in a variety of cells. A survey of A20 expression in human breast carcinoma cell lines that are either sensitive or resistant to TNF cytotoxicity revealed increased expression of A20 message and protein in TNF resistant cells. Constitutive expression of A20 after stable transfection of NIH 3T3 and WEHI 164 cells results in significant, but partial, resistance to TNF cytotoxicity. This work gives additional support to a role for TNF-induced immediate early response genes in protecting cells from TNF-induced death. PMID- 1618750 TI - Overexpression of c-myc by amplification of negative promoter domain. AB - Amplification of myc proto-oncogenes has been reported in many human malignancies, but whether the amplified genes are properly regulated has not been well studied. Transcription factors that control gene expression are of limited abundance, and we have previously shown (Johnston, R.N., and Kucey, B.L. (1988) Science 242, 1551-1554) that amplified heat shock promoter sequences can compete with natural heat shock genes for these factors, resulting in heat shock gene disregulation. To establish whether protooncogenes may also be disregulated in this manner, a previously identified negative regulatory domain from the human c myc promoter was amplified by up to 800-fold in Chinese hamster ovary cells. The amplified cells showed up to a 14-fold increase in hamster c-myc transcript abundance when compared with controls and also displayed reduced doubling times, enhanced incorporation of tritiated thymidine, elevated growth in soft agar, and a fusiform morphology, consistent with an elevation in the degree of cellular transformation. We infer that overexpression of endogenous hamster c-myc genes in the experimental cells was elicited in trans by sequestration of an inhibitory factor or complex that bound to excess nonfunctional human c-myc promoter domains. The transcriptional inhibitory activity we detect is consistent with anti-oncogene function. PMID- 1618751 TI - Specific inhibition of hepatitis B viral gene expression in vitro by targeted antisense oligonucleotides. AB - A 21-mer oligodeoxynucleotide complementary to the polyadenylation signal for human hepatitis B virus (HBV) was complexed to a soluble DNA-carrier system that is targetable to hepatocytes via asialoglycoprotein receptors present on those cells. A cell line, HepG2 (2.2.15) that possesses asialoglycoprotein receptors and is permanently transfected with hepatitis B virus (ayw subtype) was exposed to complexed antisense DNA or controls. In the presence of complexed antisense DNA, the concentration of hepatitis B surface antigen in medium was 80% lower than controls after 24 h. Furthermore, during the next 6 days, there was no significant increase in surface antigen concentration in the presence of complexed antisense DNA. The inhibition could be effectively blocked by competition with an excess of free asialoglycoprotein. Total protein synthesis remained unchanged by exposure to complexed antisense sequences under identical conditions. In addition, HBV DNA in the medium and cell layers after 24-h exposure to complexed antisense sequences was 80% lower than in controls. The data indicate that antisense oligonucleotides complexed by a soluble DNA-carrier system can be targeted to cells via asialoglycoprotein receptors resulting in specific inhibition of hepatitis B viral gene expression and replication. PMID- 1618752 TI - Stimulation of sphingomyelin biosynthesis by brefeldin A and sphingomyelin breakdown by okadaic acid treatment of rat hepatocytes. AB - Studies on sphingomyelin metabolism in rat hepatocytes were facilitated by the use of choline-deficient cells which allowed for the rapid labeling of phosphatidylcholine and as a result sphingomyelin. Pulse and pulse-chase studies with [methyl-3H]choline and [methyl-3H]methionine demonstrated that both compounds were effectively used for sphingomyelin biosynthesis and that newly made and pre-existing phosphatidylcholine could be used for sphingomyelin biosynthesis. When hepatocytes were incubated with brefeldin A, there was a 2.4 fold stimulation of the conversion of phosphatidylcholine into sphingomyelin. Since brefeldin A causes collapse of the cis/medial Golgi into the endoplasmic reticulum the stimulation of sphingomyelin biosynthesis could be due to more rapid access of the labeled phosphatidylcholine in the endoplasmic reticulum to sphingomyelin synthase in the collapsed Golgi. Forskolin inhibited the brefeldin A-induced stimulation of sphingomyelin biosynthesis. To investigate whether or not phosphorylation reactions regulate sphingomyelin metabolism, hepatocytes were incubated with okadaic acid, a potent inhibitor of protein phosphatases 1 and 2A. Rather than stimulating sphingomyelin biosynthesis, okadaic acid enhanced the catabolism of sphingomyelin. In contrast, a cyclic AMP analogue and forskolin had no effect on sphingomyelin biosynthesis or catabolism. Surprisingly, other pulse chase studies demonstrated that okadaic acid stimulated the catabolism of only newly made sphingomyelin. The brefeldin A and okadaic acid effects were independent of lysosomal involvement. Subcellular fractionation studies revealed that brefeldin A and okadaic acid effects were generalized in all sphingomyelin containing membranes. The brefeldin A studies suggest that the rate of transfer of phosphatidylcholine from the endoplasmic reticulum to the Golgi might be limiting for sphingomyelin biosynthesis. The okadaic acid studies indicate that the catabolism of sphingomyelin by a sphingomyelinase is regulated by an unidentified protein kinase and by either protein phosphatase 1 and/or 2A activity in hepatocytes. PMID- 1618753 TI - On the mechanism of oxidation of cholesterol at C-7 in a lipoxygenase system. AB - Incubation of [7-2H2]cholesterol with soybean lipoxygenase and linoleic acid in the presence of oxygen gave a mixture of 5-cholestene-3 beta,7 alpha-diol, 5 cholestene-3 beta,7 beta-diol, 3 beta-hydroxy-5-cholesten-7-one,5 alpha,6 alpha epoxycholestan-3 beta-ol, and 5 beta,6 beta-epoxycholestan-3 beta-ol. The conversion into the 7-oxygenated products was associated with a very high intermolecular isotope effect (KH/KD = 15-17), suggesting that the rate-limiting step in the overall conversion is likely to be the abstraction of hydrogen at C-7 in a radical reaction. Evidence that linoleic acid is to some extent directly involved was obtained with the use of [7-3H]cholesterol. Incubation of [7 3H]cholesterol resulted in a significant incorporation of 3H in the reisolated linoleic acid fraction. The isotope effect associated with conversion of [7 alpha 2H]cholesterol into 7-oxygenated products in the lipoxygenase system was 2-3, indicating that the extraction of hydrogen is nonstereospecific. Incubation of [7 2H2]cholesterol with 13-hydroperoxy-9,11-octadecadienoic acid gave the above 7 oxygenated products with relatively small isotope effects (KH/KD = 3-4). It is concluded that the most important mechanism for oxidation of cholesterol at C-7 in the lipoxygenase system involves participation of radicals and that a carbon centered linoleic acid radical can extract hydrogen directly from cholesterol. Fatty acid hydroperoxides and their secondary products seem to be less important as initiators in connection with oxidation of cholesterol. PMID- 1618754 TI - Identification of 5-oxo-15-hydroxy-6,8,11,13-eicosatetraenoic acid as a novel and potent human eosinophil chemotactic eicosanoid. AB - Incubation of human eosinophils with arachidonic acid led to the formation of a novel and potent eosinophil chemotactic lipid (ECL) (Morita, E., Schroder, J.-M., and Christophers, E. (1990) J. Immunol. 144, 1893-1900). To test the working hypothesis of whether ECL could have been formed via eosinophil-arachidonic acid 15-lipoxygenase we investigated whether other arachidonic acid 15-lipoxygenases such as soybean lipoxygenase I catalyze formation of a similar ECL. In the presence of hemoproteins and soybean lipoxygenase I arachidonic acid is converted to an ECL, which has physicochemical properties similar to those found for the eosinophil-derived ECL. Purification of this ECL by high performance liquid chromatography revealed that ECL is structurally different from well known eosinophil chemotactic eicosanoids such as leukotriene B4, 5,15-(6E,8Z,11Z,13E) dihydroxyeicosatetraenoic acid (5,15-diHETE), and (8S,15S)-(5Z,9E,11Z,13E) dihydroxyeicosatetra eno ic acid ((8S,15S)-diHETE). UV spectra of this ECL with absorbance maxima at 230 and 278 nm revealed the presence of two independent chromophores such as a conjugated oxodiene and a conjugated diene. Catalytic hydrogenation of ECL methyl ester led to the formation of 5,15-dihydroxyarachidic acid methyl ester. Reduction of ECL with sodium borohydride produced a product which is identical with authentic (5S,15S)-(6E,8Z,11Z,13E)-diHETE. Formation of an ECL monomethoxime derivative supports the conclusion that this highly potent eosinophil chemotactic eicosanoid is structurally identical with 5-oxo-15-hydroxy 6,8,11,13-eicosatetraenoic acid. PMID- 1618755 TI - Purification and characterization of the photosystem I complex from the filamentous cyanobacterium Anabaena variabilis ATCC 29413. AB - A photoactive photosystem I complex has been purified from the filamentous, nitrogen-fixing cyanobacterium Anabaena variabilis ATCC 29413. Cells were broken using glass beads, and the membrane fraction was solubilized with beta-dodecyl maltoside followed by two rounds of fast protein liquid chromatography on anion exchange columns. The polypeptide composition of the isolated complex was determined by sodium dodecyl sulfate-urea-polyacrylamide gel electrophoresis and N-terminal amino acid sequencing of the fractionated proteins. The purified complex consists of at least 11 proteins, identified as the PsaA, PsaB, PsaC, PsaD, PsaE, PsaF, PsaI, PsaJ, PsaK, PsaL, and PsaN proteins. The spectrum of the flash-induced absorbance change measured between 670 and 830 nm shows that the purified complex contains 99 +/- 11 chlorophyll a molecules per P700, the primary donor in photosystem I. The kinetics of the rereduction of oxidized P700 following an actinic flash indicate that forward electron transfer from P700 to the FA/FB iron-sulfur center acceptors is functional in the isolated complex. PMID- 1618756 TI - A synthetic sialic acid analogue is recognized by influenza C virus as a receptor determinant but is resistant to the receptor-destroying enzyme. AB - Synthetic sialic acid analogues varying in the substitutents at position C-9 were analyzed for their ability to replace the natural receptor determinant for influenza C virus, N-acetyl-9-O-acetylneuraminic acid (Neu5,9Ac2). By incubation of erythrocytes with sialyltransferase and the CMP-activated analogues, the cell surface was modified to contain sialic acid with one of the following C-9 substituents: an azido, an amino, an acetamido, or a hexanoylamido group. Among these, only 9-acetamido-N-acetylneuraminic acid (9-acetamido-Neu5Ac) was able to function as a receptor determinant for influenza C virus as indicated by the ability of the virus to agglutinate the modified red blood cells. In contrast to the natural receptors, 9-acetamido-Neu5Ac-containing receptors were found to be resistant against the action of sialate 9-O-acetylesterase, the viral receptor destroying enzyme. No difference in the hemolytic activity of influenza C virus was detected when analyzed with erythrocytes containing either Neu5,9Ac2 or 9 acetamido-Neu5Ac on their surface. This finding indicates that cleavage of the receptor is not required for the viral fusion activity. The sialic acid analogues should be useful for analyzing not only the importance of the receptor-destroying enzyme of influenza C virus, but also other biological processes involving sialic acid. PMID- 1618757 TI - The primary structure of omega-amino acid:pyruvate aminotransferase. AB - The complete amino acid sequence of bacterial omega-amino acid:pyruvate aminotransferase (omega-APT) was determined from its primary structure. The enzyme protein was fragmented by CNBr cleavage, trypsin, and Staphylococcus aureus V8 digestions. The peptides were purified and sequenced by Edman degradation. omega-ATP is composed of four identical subunits of 449 amino acids each. The calculated molecular weight of the enzyme subunit is 48,738 and that of the enzyme tetramer is 194,952. No disulfide bonds or bound sugar molecules were found in the enzyme structure, although 6 cysteine residues were determined per enzyme subunit. Sequence homologies were found between an omega-aminotransferase, i.e. mammalian and yeast ornithine delta-aminotransferases, fungal gamma aminobutyrate aminotransferase and 7,8-diaminoperalgonate aminotransferase, and 2,2-dialkylglycine decarboxylase. The enzyme structure is not homologous to those of aspartate aminotransferases (AspATs) including the enzymes of Escherichia coli and Sufolobus salfactaricus, though significant homology in the three-dimensional structures around the cofactor binding site has been found between omega-APT and AspATs (Watanabe, N., Sakabe, K., Sakabe, N., Higashi, T., Sasaki, K., Aibara, S., Morita, Y., Yonaha, K., Toyama, S., and Fukutani, H. (1989) J. Biochem. 105, 1-3). PMID- 1618758 TI - Role of the antithrombin-binding pentasaccharide in heparin acceleration of antithrombin-proteinase reactions. Resolution of the antithrombin conformational change contribution to heparin rate enhancement. AB - The synthetic antithrombin-binding heparin pentasaccharide and a full-length heparin of approximately 26 saccharides containing this specific sequence have been compared with respect to their interactions with antithrombin and their ability to promote inhibition and substrate reactions of antithrombin with thrombin and factor Xa. The aim of these studies was to elucidate the pentasaccharide contribution to heparin's accelerating effect on antithrombin proteinase reactions. Pentasaccharide and full-length heparins bound antithrombin with comparable high affinities (KD values of 36 +/- 11 and 10 +/- 3 nM, respectively, at I 0.15) and induced highly similar protein fluorescence, ultraviolet and circular dichroism changes in the inhibitor. Stopped-flow fluorescence kinetic studies of the heparin binding interactions at I 0.15 were consistent with a two-step binding process for both heparins, involving an initial weak encounter complex interaction formed with similar affinities (KD 20 30 microM), followed by an inhibitor conformational change with indistinguishable forward rate constants of 520-700 s-1 but dissimilar reverse rate constants of approximately 1 s-1 for the pentasaccharide and approximately 0.2 s-1 for the full-length heparin. Second order rate constants for antithrombin reactions with thrombin and factor Xa were maximally enhanced by the pentasaccharide only 1.7 fold for thrombin, but a substantial 270-fold for factor Xa, in an ionic strength independent manner at saturating oligosaccharide. In contrast, the full-length heparin produced large ionic strength-dependent enhancements in second order rate constants for both antithrombin reactions of 4,300-fold for thrombin and 580-fold for factor Xa at I 0.15. These enhancements were resolvable into a nonionic component ascribable to the pentasaccharide and an ionic component responsible for the additional rate increase of the larger heparin. Stoichiometric titrations of thrombin and factor Xa inactivation by antithrombin, as well as sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the products of these reactions, indicated that pentasaccharide and full-length heparins similarly promoted the formation of proteolytically modified inhibitor during the inactivation of factor Xa by antithrombin, whereas only the full-length heparin was effective in promoting this substrate reaction of antithrombin during the reaction with thrombin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1618759 TI - The cDNA for the type I iodothyronine 5'-deiodinase encodes an enzyme manifesting both high Km and low Km activity. Evidence that rat liver and kidney contain a single enzyme which converts thyroxine to 3,5,3'-triiodothyronine. AB - The enzymatic conversion of thyroxine (T4) to 3,5,3-triiodothyronine (T3) by iodothyronine 5'-deiodinase(s) is an obligate step in the physiologic action of thyroid hormones in most extrathyroidal tissues. In the rat liver and kidney, 5' deiodinase processes having either high Km (micromolar range) or low Km (nanomolar range) values for thyroid hormone substrates have been described. The number of enzymes mediating these reactions, however, remains uncertain and controversial. To examine this question we have compared the 5'-deiodinase activity expressed in membrane preparations of Xenopus laevis oocytes after the injection of either rat liver poly(A)+ RNA or in vitro prepared RNA transcribed using the G21 full-length type I 5'-deiodinase cDNA. In oocytes injected with rat liver poly(A)+ RNA, high Km (i.e. type I) activity was observed when 20 mM dithiothreitol was used as the thiol cofactor, whereas Km values in the nanomolar range were noted with 0.5 mM dithiothreitol, glutathione, or a reconstituted thioredoxin cofactor system. This complex pattern of 5'-deiodinase activity, which mimics that found in homogenates and subcellular fractions of rat liver and kidney, was reproduced exactly in oocytes by the microinjection of G21-derived RNA transcripts. Furthermore, hybrid arrest of translation in oocytes using a partial type I 5'-deiodinase cDNA completely inhibited the expression of both high and low Km activity after the injection of rat liver poly(A)+ RNA. These findings demonstrate that rat liver and kidney contain only a single 5' deiodinase which manifests either high or low Km activity depending on the reduced thiol cofactor utilized in the reaction. PMID- 1618761 TI - Stereoselective hydrolysis catalyzed by related beta-1,4-glucanases and beta-1,4 xylanases. AB - Over 80 beta-1,4-glucanases and beta-1,4-xylanases can be classified into one of eight families on the basis of amino acid sequence similarities in their catalytic domains (Gilkes, N. R., Henrissat, B., Kilburn, D. G., Miller, R. C., Jr., and Warren, R. A. J. (1991) Microbiol. Rev. 55, 303-315). As a test of this classification, the stereochemical course of hydrolysis of 10 enzymes representative of five families has been determined using proton NMR. These data, together with published data for six additional enzymes, show that representatives of a given enzyme family have the same stereoselectivity: four families catalyze hydrolysis with retention of anomeric configuration, two with inversion. The results support the hypothesis that family members share a common general fold, active site topology, and catalytic mechanism. PMID- 1618760 TI - Identification and expression of five mutations in the human acid sphingomyelinase gene causing types A and B Niemann-Pick disease. Molecular evidence for genetic heterogeneity in the neuronopathic and non-neuronopathic forms. AB - The deficient activity of the human lysosomal hydrolase, acid sphingomyelinase (ASM, EC 3.1.4.12), results in the neuronopathic (Type A) and non-neuronopathic (Type B) forms of Niemann-Pick disease (NPD). To investigate the genetic basis of the phenotypic heterogeneity in NPD, the molecular lesions in the ASM gene were determined from three unrelated NPD patients and evaluated by transient expression in COS-1 cells. A Type A NPD patient of Asian Indian ancestry (proband 1) was homoallelic for a T to A transversion in exon 2 of the ASM gene which predicted a premature stop at codon 261 of the ASM polypeptide (designated L261X). In contrast, an unrelated Type A patient of European ancestry (proband 2) was heteroallelic for a two-base (TT) deletion in exon 2 which caused a frame shift mutation at ASM codon 178 (designated fsL178), leading to a premature stop at codon 190, and a G to A transition in exon 3 which caused a methionine to isoleucine substitution at codon 382 (designated M382I). Transient expression of the fsL178, L261X, and M382I mutations in COS-1 cells demonstrated that these lesions did not produce catalytically active ASM, consistent with the severe neuronopathic Type A NPD phenotype. In contrast, an unrelated Type B patient of European descent (proband 3) was heteroallelic for two missense mutations, a G to A transition in exon 2 which predicted a glycine to arginine substitution at ASM codon 242 (designated G242R), and an A to G transition in exon 3 which resulted in an asparagine to serine substitution at codon 383 (designated N383S). Interestingly, the G242R allele produced ASM activity in COS-1 cells at levels about 40% of that expressed by the normal allele, thereby explaining the mild Type B phenotype of proband 3 and the high residual activity (i.e. approximately 15% of normal) in cultured lymphoblasts. In contrast, the N383S allele did not produce catalytically active enzyme. None of these five ASM mutations was detected in over 60 other unrelated NPD patients analyzed, nor were these mutations found in over 100 normal ASM alleles. Thus, small deletions or nonsense mutations which trunctated the ASM polypeptide, or missense mutations that rendered the enzyme noncatalytic, resulted in Type A NPD disease, whereas a missense mutation that produced a defective enzyme with residual catalytic activity caused the milder nonneuronopathic Type B phenotype. These findings have facilitated genotype/phenotype correlations for this lysosomal storage disease and provided insights into the functional organization of the ASM polypeptide. PMID- 1618762 TI - Golgi vacuolization and immunotoxin enhancement by monensin and perhexiline depend on a serum protein. Implications for intracellular trafficking. AB - Vacuole formation around the Golgi and immunotoxin enhancement induced by low doses of the ionophore monensin were inhibited by 50% human plasma (final concentration), whereas the lysosomal pH increase remained unaffected. Immunotoxin enhancement by the Ca2+ antagonist perhexiline was also inhibited by plasma. The inhibiting factor was present in different species and highly concentration-dependent. After purification on DEAE- and CM-Sepharose it showed a heterogeneous distribution between 45 and 50 kDa, in sodium dodecyl sulfate polyacrylamide gel electrophoresis, an extreme isoelectric point near 3.5, and binding to wheat germ agglutinin-Sepharose. Maximum inhibition was found in the lower molecular mass fraction of 45 kDa. The 50-kDa fraction, although showing immunological identity reactions, remained almost inactive. The simultaneous inhibition of morphological alterations and the enhancement of immunotoxin activity by the highly enriched protein provides a first direct link between both events. Apart from a role of this serum glycoprotein on in vivo inhibition of immunotoxin enhancement, its ability to maintain normal intracellular trafficking in the presence of blocking agents, such as monensin and perhexiline, suggests a more fundamental role in the regulation of these mechanisms. PMID- 1618763 TI - Expression of cytochrome b5 in yeast and characterization of mutants of the membrane-anchoring domain. AB - The soluble and membrane-bound forms of the synthetic rat cytochrome b5 gene have been expressed in Saccharomyces cerevisiae. In order to examine the topology and function of the COOH-terminal membrane binding domain of cytochrome b5, mutants have been constructed, expressed, purified, and partially characterized. Pro-115 is located in the middle of the putative alpha-helical membrane-anchoring domain of cytochrome b5 and has been hypothesized to give rise to either a hairpin-like loop or approximately equal to 26 degrees kink in the helix, depending on whether it exists, respectively, in the cis or trans configuration. The Pro-115----Ala mutant, which is expected to have a straight transmembrane helix, inserted normally into the endoplasmic reticulum and exhibited wild type levels of activity in yeast microsomes and in vitro in the cytochrome P-450 mixed function oxidation system. Since a hairpin structure does not appear to be essential, it is likely that the membrane binding domain of cytochrome b5 spans the membrane. Characterization of the truncated cytochrome b5 molecule, Pro-115----Stop, lacking 19 amino acids at the COOH terminus indicates that the distal part of the membrane binding domain of cytochrome b5 is necessary for in vivo binding to the endoplasmic reticulum and for functioning with its membrane-associated electron transfer partners. Replacement of Ser-104 to Met-125, the putative membrane anchoring domain of cytochrome b5, with 22 leucine residues results in a protein which targets to the endoplasmic reticulum but the extent of its reduction is only 50% of that of the wild type in yeast microsomes. In vitro, the polyleucine mutant is unable to support substrate oxidation by cytochrome P-450. The mutation of Ala-131 and Glu-132, amino acids flanking the transmembrane domain, to lysines resulted in a protein with normal membrane topology and function. PMID- 1618764 TI - Alpha-isoenzyme of alcohol dehydrogenase from monkey liver. Cloning, expression, mechanism, coenzyme, and substrate specificity. AB - The cDNA for the alpha-isoenzyme from rhesus monkey (Macaca mulatta) liver was cloned and expressed in yeast. The alpha-isoenzymes of human and monkey liver alcohol dehydrogenase differ from the other human and horse liver enzymes in having Met57, Ala93, and Val116 instead of Leu57, Phe93, and Leu116 in the substrate binding pocket and Gly47 instead of Arg47 near the pyrophosphate moiety of the coenzyme. The effects of these differences on the kinetic mechanism, substrate specificity, and coenzyme binding were studied with the purified, recombinant monkey alpha-isoenzyme (MmADH alpha) and mutated enzymes with Gly47 substituted with His or Arg. The mechanism appears to be random for the binding of NAD+ and ethanol and ordered for NADH and acetaldehyde, with formation of a dead-end enzyme-NADH-ethanol complex. MmADH alpha reacts 130-fold slower (V/K) with ethanol and 3-25-fold slower with 2-methyl alcohols but 20-fold faster with cyclohexanol, as compared with horse (Equus caballus) liver EE isoenzyme (EqADH). MmADH alpha is stereoselective for the R isomer of 2-butanol, whereas EqADH favors the S isomer. Both enzymes have comparable reactivity with larger primary alcohols. MmADH alpha is more reactive with secondary alcohols and has highest activity with cyclohexanol. However, it does not react with steroids such as 5 beta-androstane-17 beta-ol-3-one. Molecular modeling suggests that the differences between MmADH alpha and EqADH are a result of the substitution of Ala for Phe93 and Thr for Ser48. MmADH alpha binds NAD+ most rapidly when a group with a pK of 7.4 is unprotonated, implicating His51 in this reaction. The G47R substitution decreased the dissociation constants for NAD+ and NADH and turnover numbers only about 2-fold, whereas the G47H substitution increased dissociation constants 7-14-fold and turnover numbers 4-fold. A basic residue at position 47 is not crucial for activity, as multiple interactions determine coenzyme affinity. PMID- 1618765 TI - Reversible stepwise mechanism involving a carbanion intermediate in the elimination of ammonia from L-histidine catalyzed by histidine ammonia-lyase. AB - L-Histidine labeled with deuterium at the C-5' position of the imidazole ring, L [5'-2H]histidine (His-5'-D), was used as a probe for investigating a stepwise reversible mechanism via a carbanion intermediate in the elimination of ammonia catalyzed by histidine ammonia-lyase (EC 4.3.1.3). The labeled L-histidine (His 5'-D) (2.45 mM) was incubated with histidine ammonia-lyase (200 units) from Pseudomonas fluorescens at pH 7.0 or 9.0 at 25.0 degrees C for 24 h. The time course of the reaction was examined to determine the rates of enzyme-catalyzed hydrogen exchange at C-5' of L-histidine and urocanic acid. The finding of the enzyme-catalyzed hydrogen exchange at C-5' of both L-histidine and urocanic acid in the presence of L-histidine provided a rational explanation for a stepwise reversible mechanism via a carbanion intermediate in the elimination reaction. The rate of increase in the concentration of urocanic acid exchanged with hydrogen (UA-5'-H) did not depend on the formation rate of urocanic acid and UA 5'-H was continuously formed at a constant rate (25.6 microM/h) even after the completion of urocanic acid formation. These observations suggested the presence of the reversible reaction of urocanic acid and a carbanion intermediate. Since there was only a minor contribution for the formation of UA-5'-H from L-histidine exchanged with solvent hydrogen (His-5'-H), the main pathway in the enzymatic reaction of His-5'-D must be the formation of UA-5'-D via a carbanion intermediate (carbanion-D). Regeneration of the carbanion-D from UA-5'-D by its reverse reaction and subsequent hydrogen incorporation at C-5' would contribute to a large extent for the formation of UA-5'-H. The stability of carbanion was also demonstrated to be approximately three times higher at pH 7.0 than at pH 9.0. PMID- 1618767 TI - Escherichia coli ribonucleotide reductase. Radical susceptibility to hydroxyurea is dependent on the regulatory state of the enzyme. AB - Ribonucleotide reductase catalyzes the reduction of ribonucleotides to their corresponding deoxyribonucleotides via a radical-mediated mechanism. The enzyme from Escherichia coli consists of the two non-identical proteins, R1 and R2, the latter of which contains the necessary free radical located to a tyrosine residue. The radical scavenger hydroxyurea was found to reduce the tyrosyl radical of R2 in a second-order reaction. The rate constant (0.50 M-1 s-1 at 25 degrees C) for this process was several orders of magnitude lower than the hydroxyurea-dependent reduction of free tyrosyl radicals in solution. This difference probably reflects the fact that the R2 tyrosyl radical is buried in the interior of the protein. Formation of the R1R2 complex changed the susceptibility of the radical to hydroxyurea in a manner that reflects the regulatory state of the holoenzyme. Furthermore, binding of substrate or product to the holoenzyme complex made the R2 radical at least 10 times more susceptible to inactivation by hydroxyurea than it was in the isolated R2 protein. One active site mutation in the R1 protein was shown to affect the sensitivity of the tyrosyl radical of R2 differently than wild type protein R1 does. Our results clearly show that the susceptibility of the tyrosyl radical in R2 to inactivation by hydroxyurea can be used as an efficient probe for the regulatory state of the holoenzyme complex. PMID- 1618766 TI - Structure and ligand binding properties of leucine 29(B10) mutants of human myoglobin. AB - Site-specific mutants of human myoglobin (Mb) have been prepared, in which Leu29 (B10) is replaced by Ala(L29A) or Ile(L29I), in order to examine the influence of this highly conserved residue in the hydrophobic clusters of the heme distal site on the heme environmental structure and ligand binding properties of Mb. Structural characterizations of these recombinant Mbs are studied by electronic absorption, infrared (IR), one- and two-dimensional proton nuclear magnetic resonance spectroscopies, and ligand-binding kinetics by laser photolysis measurements under ambient and high pressures (up to 2000 bar). Multiple split carbon monoxide (CO) stretch bands in the IR spectra of mutant Mbs exhibit a relative decrease of the 1945 cm-1 band (approximately 50%) which is associated with an upright binding geometry of CO, accompanied by an increase of the tilted CO conformer at 1932 cm-1. On the basis of these results, replacement of Leu29(B10) by Ala or Ile appears to allow bound CO to rotate from a conformation pointing toward the beta meso carbon of the heme group to the one pointing toward the alpha meso carbon atom, presumably filling the space left by removal of the delta 2 carbon atom of Leu29(B10). These substitutions cause the rate constants for CO and O2 association to decrease almost 3-5-fold. Present results show that CO and O2 bindings to the heme iron of Mb are controlled by Leu29(B10) by influencing the structure of close vicinity of the heme and the geometry of iron bound ligand. Further, mutant Mbs (Leu72(E15)----Ala and Leu104 (G5)----Ala) which have altered residues in another hydrophobic clusters around proximal and distal site are also examined. PMID- 1618768 TI - Caracemide, a site-specific irreversible inhibitor of protein R1 of Escherichia coli ribonucleotide reductase. AB - The anticancer drug caracemide, N-acetyl-N,O- di(methylcarbamoyl)hydroxylamine, and one of its degradation products, N-acetyl-O-methylcarbamoyl-hydroxylamine, were found to inhibit the enzyme ribonucleotide reductase of Escherichia coli by specific interaction with its larger component protein R1. No effect on the smaller protein R2 was observed. The effect of the degradation product was about 30 times lower than that of caracemide itself. The caracemide inactivation of R1 is irreversible, with an apparent second-order rate constant of 150 M-1 s-1. The R1R2 holoenzyme was approximately 30 times more sensitive to caracemide inactivation than the isolated R1 protein. The ribonucleotide reductase substrates were potent competitors of the caracemide inhibition, with a Kdiss for GDP binding to R1 of 80 microM. The reducing agent dithiothreitol was also found to be a potent competitor of caracemide inactivation. These results indicate that caracemide inactivates R1 by covalent modification at the substrate-binding site. By analogy with the known interaction between caracemide and acetylcholinesterase or choline acetyltransferase, we propose that the modification of R1 occurs at an activated cysteine or serine residue in the active site of the enzyme. PMID- 1618769 TI - O-acetylated gangliosides in bovine buttermilk. Characterization of 7-O-acetyl, 9 O-acetyl, and 7,9-di-O-acetyl GD3. AB - Three O-acetylated gangliosides, G1, G2, and G3, were purified from bovine buttermilk by using chloroform/methanol extraction, Folch partitioning, chromatography on DEAE-Sephadex A-25, and Iatrobeads columns. The final yields of gangliosides G1, G2, and G3 were 2 mg, 37 mg, and 40 mg per 1.7 kg of the buttermilk powder, respectively. On the basis of immunostaining on high performance thin layer chromatography with specific monoclonal antibodies, mild alkaline treatment, gas-liquid chromatographic analysis, fast atom bombardment mass spectrometry, and proton nuclear magnetic resonance studies, G1 and G2 are characterized as O-acetylated GD3 and G3 as O-acetylated GT3, and the structures of these gangliosides are as follows: [formula: see text] The major fatty acids of these gangliosides were C18:0, C22:0, C23:0, and C24:0, and the long chain base was C18-sphingosine. PMID- 1618770 TI - Post-transcriptional regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase by 24(S),25-oxidolanosterol. AB - We have examined the mechanism of regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase by 24(S),25-oxidolanosterol, a C30-sterol naturally occurring in mammalian tissues. In the absence of enzymatic demethylation to the C27-sterol, 24(S),25-epoxycholesterol, oxidolanosterol is shown to be a post transcriptional regulator of reductase synthesis in both primary rat hepatocytes and Chinese hamster ovary cells. Under these conditions, oxidolanosterol also increases the rate of degradation of reductase protein in these cells. When demethylation is not inhibited, oxidolanosterol treatment produces transcriptional regulation of sterol-sensitive genes in Chinese hamster ovary cells. In contrast to previous findings with the oxygenated C27-sterol, 25 hydroxycholesterol, oxidolanosterol can act as a post-transcriptional regulator in cells starved for mevalonate. These findings are consistent with the hypothesis that oxidolanosterol down-regulates sterol synthesis in a fashion mechanistically distinct from that of C27-sterols. PMID- 1618771 TI - Preparation, purification, and determination of the biological activities of 12 N terminus-truncated recombinant analogues of bovine placental lactogen. AB - Removal of 13 to 15 amino acids from the N terminus of bovine placental lactogen (bPL), which according to the three-dimensional structure of pGH corresponds to a nonhelical part of bPL, did not effect its secondary structure or change the monomer content of the protein preparation. However, it remarkably decreased the binding of the prolactin (PRL) type of receptors on Nb2 cells with subsequent reduction in bioactivity. The binding to the growth hormone (somatogen) receptors either did not change or was increased, resulting in an increase of somatogen receptor-mediated bioactivity. Further truncation (17-18 amino acids) resulted in a decrease of alpha-helical content and loss of binding properties and biological activity mediated through interaction of the analogues with both somatogen (3T3 F442A cells) and lactogen (PRL) receptors (NB2-11C cells). Truncation of 19-27 amino acids caused additional loss in activity, without further change in the secondary structure. Replacement of Leu28 by a more hydrophobic Phe has only minor, if any, effect on the bioactivity of bPL. Occasional point mutations due to polymerase chain reaction errors in several analogues did not seem to have any major effect on the hormone properties. It can thus be suggested that the N terminal part of the nonhelical portion of bPL, which corresponds to the portion of the molecule that does not exist in growth hormones, is required for efficient binding to the lactogen (PRL) but not to the somatogen or unique bPL receptors. Removal of the N-terminal part of pBL changed the specificity of bPL by decreasing its PRL receptor-mediated activities and increasing its somatogen receptor-mediated activities. PMID- 1618772 TI - Small-angle x-ray scattering study of metal ion-induced conformational changes in Serratia protease. AB - Metal ion-induced conformational changes in Serratia protease which contains one zinc ion per molecule were investigated by the small-angle x-ray scattering method. The molecule is an elongated ellipsoid of approximately 110 x 40 x 40 A with a large cleft in its central region. Comparisons of the native (zinc-enzyme) with the zinc-free (apoenzyme) enzyme and with the zinc-replated metalloenzyme show small but significant differences in their radii of gyration, maximum particle dimensions, and intraparticle pair-distance distributions. The radius of gyration and maximum particle dimension of the native enzyme are almost the same as those of the cobalt-enzyme but are shorter and longer, respectively, than those of the apo- and cadmium-enzymes. Simulation analysis based on the intraparticle pair-distribution function showed that these modified enzymes are comparable with the native enzyme in overall structure, and, except for the cobalt-enzyme, differ in cleft size. The residual enzymatic activity of the cobalt-enzyme is the same as that of the native enzyme, but the apo- and cadmium enzymes have considerably less activity. The size of the cleft therefore is strictly controlled to ensure optimal enzyme activity, and the position and coordination behavior of the zinc ion in the cleft appears to be essential both for biological functioning and for the maintenance of the gross tertiary structure. PMID- 1618773 TI - Role of carnitine and carnitine palmitoyltransferase as integral components of the pathway for membrane phospholipid fatty acid turnover in intact human erythrocytes. AB - The deacylation and reacylation process of phospholipids is the major pathway of turnover and repair in erythrocyte membranes. In this paper, we have investigated the role of carnitine palmitoyltransferase in erythrocyte membrane phospholipid fatty acid turnover. The role of acyl-L-carnitine as a reservoir of activated acyl groups, the buffer function of carnitine, and the importance of the acyl CoA/free CoA ratio in the reacylation process of erythrocyte membrane phospholipids have also been addressed. In intact erythrocytes, the incorporation of [1-14C]palmitic acid into acyl-L-carnitine, phosphatidylcholine, and phosphatidylethanolamine was linear with time for at least 3 h. The greatest proportion of the radioactivity was found in acyl-L-carnitine. Competition experiments using [1-14C]palmitic and [9,10-3H]oleic acid demonstrated that [9,10 3H]oleic acid was incorporated preferentially into the phospholipids and less into acyl-L-carnitine. When an erythrocyte suspension was incubated with [1 14C]palmitoyl-L-carnitine, radiolabeled palmitate was recovered in the phospholipid fraction, and the carnitine palmitoyltransferase inhibitor, 2 tetradecylglycidic acid, completely abolished the incorporation. ATP depletion decreased incorporation of [1-14C]palmitic and/or [9,10-3H]oleic acid into acyl-L carnitine, but the incorporation into phosphatidylcholine and phosphatidylethanolamine was unaffected. In contrast, ATP depletion enhanced the incorporation into phosphatidylcholine and phosphatidylethanolamine of the radiolabeled fatty acid from [1-14C]palmitoyl-L-carnitine. These data are suggestive of the existence of an acyl-L-carnitine pool, in equilibrium with the acyl-CoA pool, which serves as a reservoir of activated acyl groups. The carnitine palmitoyltransferase inhibition by 2-tetradecylglycidic acid or palmitoyl-D-carnitine caused a significant reduction of radiolabeled fatty acid incorporation into membrane phospholipids, only when intact erythrocytes were incubated with [9,10-3H]oleic acid. These latter data may be explained by the differences in rates and substrates specificities between acyl-CoA synthetase and the reacylating enzymes for palmitate and oleate, which support the importance of carnitine palmitoyltransferase in modulating the optimal acyl-CoA/free CoA ratio for the physiological expression of the membrane phospholipids fatty acid turnover. PMID- 1618774 TI - Hemoglobin Thionville. An alpha-chain variant with a substitution of a glutamate for valine at NA-1 and having an acetylated methionine NH2 terminus. AB - In hemoglobin (Hb) Thionville, the substitution of a glutamic acid for the alpha chain NH2-terminal valine inhibits the cleavage of the initiator methionine which is then acetylated. The elongation of the alpha-chain NH2 terminus modifies the three-dimensional structure of hemoglobin at a region that is known to have an important role in the allosteric regulation of oxygen binding. Relative to Hb A, Hb Thionville has a lower affinity for oxygen, and the heterotropic allosteric effects of protons, chloride, and bezafibrate are reduced. In contrast, the response to 2,3-diphosphoglycerate is normal. Analysis of oxygen equilibrium data within the framework of the two-state allosteric model indicates that the structure of deoxy Hb Thionville is stabilized relative to that of deoxy Hb A. The x-ray crystal structure of deoxy Hb Thionville shows that the glutamate side chain extends away from the alpha 1-alpha 2 interface, whereas the methionine side chain (which has two conformations) extends into the alpha 1-alpha 2 interface, physically displacing chloride and bezafibrate. The increased stability of deoxy Hb Thionville is due to new intrasubunit and intersubunit contacts made by the methionine. These interactions replace the indirect contacts, made through bound chloride ions, that Val-1 alpha normally contributes to the alpha 1-alpha 2 interface. PMID- 1618775 TI - Purification and characterization of a UDP-GalNAc:polypeptide N acetylgalactosaminyltransferase specific for glycosylation of threonine residues. AB - A UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase from porcine submaxillary glands was purified to electrophoretic homogeneity. IgG prepared from antisera against the pure enzyme immunoprecipitated the transferase in Triton X-100 extracts of submaxillary glands. The submaxillary transferase is a membrane-bound enzyme in contrast to the pure bovine colostrum enzyme, which is soluble in the absence of detergents. Both transferases have similar properties but also differ significantly. Examination of the acceptor substrate specificity of the submaxillary gland transferase showed that it specifically transferred N acetylgalactosamine from UDP-GalNAc to the hydroxyl group of threonine and was devoid of transferase activity toward serine-containing peptides. These results imply that more than one transferase is involved in forming the GalNAc-threonine and the GalNAc-serine linkages found in O-linked oligosaccharides in glycoproteins. The amino acid sequence adjacent to glycosylated threonine residues may influence the rate of glycosylation by the pure transferase. For example, the second threonine residue in the sequence, Thr-Thr, appears to be glycosylated about twice as fast as the first and more rapidly than single, isolated threonine residues. However, no unique consensus sequence for glycosylation of threonine residues is evident, and any accessible threonine residue appears to be a potential acceptor substrate. PMID- 1618776 TI - Diversity of immunodominant 56-kDa type-specific antigen (TSA) of Rickettsia tsutsugamushi. Sequence and comparative analyses of the genes encoding TSA homologues from four antigenic variants. AB - There are several antigenic variants in Rickettsia tsutsugamushi, and a type specific antigen (TSA) of 56-kilodaltons located on the rickettsial surface is responsible for the variation. The primary structures of the protein in two variants, Gilliam and Karp, have been reported independently by us and Stover et al. by cloning and sequencing the corresponding genes (Ohashi, N., Nashimoto, H., Ikeda, H., and Tamura, A. (1990) Gene (Amst.) 91, 119-122; Stover, C. K., Marana, D. P., Carter, J. M., Roe, B. A., Mardis, E., and Oaks, E. V. (1990) Infect. Immun. 58, 2076-2084). In the present study, genes encoding the TSA homologues of the other four variants, Kato, Kawasaki, Kuroki, and Shimokoshi, which are all distinguishable serologically, were cloned and sequenced, and consequently, it became possible to compare the primary structures of the six antigenic variants. The sequence analyses revealed a complete open reading frame encoding 55,308 56,745-dalton proteins with 521-532 amino acids, in which a putative signal peptide consisting of 22 amino acids was recognized at the NH2-terminal end. Transcription of the gene is regulated by several tandem promoters. All TSA molecules have the characteristics of transmembrane proteins with alternating hydrophobic and hydrophilic regions, and contain four variable domains with spans of 16-40 amino acids which are located in the hydrophilic regions in the molecule and show different amino acid sequences among the strains. Phylogenetic classification among the R. tsutsugamushi strains based on TSA homologues supports the antigenic relationships known in the closely and distantly related strains. PMID- 1618777 TI - Adipsin and an endogenous pathway of complement from adipose cells. AB - The alternative complement pathway is best known for its role in humoral suppression of infectious agents. We have previously shown that adipose cells synthesize adipsin, the mouse homolog of human complement factor D, and that the synthesis of this protein is reduced in several rodent models of obesity. We show here that adipose cells and adipose tissue also synthesize two other essential components of the alternative pathway of complement, factors C3 and B, and activate the proximal portion of this pathway. This activation occurs in the absence of infectious agents and without triggering the terminal, lytic part of this pathway. We demonstrate the production in vitro of several polypeptides characteristic of complement activation that are known to have potent biological activities, including the anaphylatoxin C3a. Cultured adipocytes require stimulation with cytokines to activate complement, while explanted adipose tissue has no such requirement. The adipose tissue from obese mice is deficient in this localized activation of the alternative pathway. These results indicate that complement activation occurs in a localized site, adipose tissue, in normal mice and is impaired in a state of metabolic dysfunction. This suggests a novel function for the proximal portion of this complement pathway related to adipose cell biology or energy balance. PMID- 1618778 TI - Calcium is required for folding of newly made subunits of the asialoglycoprotein receptor within the endoplasmic reticulum. AB - By resolving immunoprecipitates on nonreducing sodium dodecyl sulfate gels, we have detected several disulfide-bonded intermediates in folding within the endoplasmic reticulum of newly made H1 subunits of the asialoglycoprotein receptor. H1 in the endoplasmic reticulum (ER) can be partially unfolded by treatment of cells with dithiothreitol, but H1 in Golgi or post-Golgi organelles is resistant to such unfolding. This defines a late step in H1 folding that occurs just prior to exit from the ER. Depletion of calcium from the endoplasmic reticulum, either by treatment with A23187 or thapsigargin, has no effect on folding or secretion of newly made albumin, but totally blocks H1 maturation from the ER. No ER intermediates in H1 folding are formed in cells treated with A23187 or thapsigargin, indicating that at least an early step in H1 folding requires a high Ca2+ concentration in the ER lumen. As judged by cross-linking experiments, formation of H1 dimers and trimers occurs immediately after biosynthesis of the peptide chain, before monomer folding, and occurs normally in cells in which ER Ca2+ is reduced and where the monomer never folds properly. Calcium is essential for the asialoglycoprotein receptor to bind galactose, and our results suggest that Ca2+ is also essential for the receptor polypeptides to fold in the ER. PMID- 1618779 TI - Purification and properties of the F sex factor TraD protein, an inner membrane conjugal transfer protein. AB - Using a traD overexpression plasmid, we purified the F sex factor TraD protein in milligram quantities. The purified protein has an apparent molecular weight of 82,000 and an amino acid composition rich in acidic residues. Using specific antibodies, TraD was localized to the inner membrane of F+ cells under conditions where it is produced in physiologically normal amounts. Furthermore, the protein was soluble only in the presence of detergents, but there is evidence that the carboxyl terminus is water-soluble. The purified protein shows pH-sensitive binding to DNA cellulose columns. PMID- 1618780 TI - Enhanced insulin-induced mitogenesis and mitogen-activated protein kinase activities in mutant insulin receptors with substitution of two COOH-terminal tyrosine autophosphorylation sites by phenylalanine. AB - We have studied the function of a mutant human insulin receptor in which two COOH terminal autophosphorylation sites (Tyr-1316 and -1322) were replaced by phenylalanine (F/Y COOH-terminal 2 tyrosines (CT2)). In addition, we have also constructed a mutant receptor in which Lys-1018 in the ATP-binding site was changed to arginine (R/K 1018). Both the wild type insulin receptor (HIR) and the mutant receptors were expressed in Chinese hamster ovary (CHO) cells by stable transfection. Autophosphorylation of solubilized and partially purified F/Y CT2 was decreased by approximately 30% compared with the HIR. Tyrosine kinase activities of F/Y CT2 and HIR toward exogenous substrates were almost equal. When CHO cells transfected with F/Y CT2 (CHO-F/Y CT2) were stimulated with insulin, autophosphorylation of the beta-subunit of the insulin receptor and the phosphorylation of an endogenous substrate (pp185) in the intact cell were normal compared with cells expressing HIR (CHO-HIR). CHO-F/Y CT2 exhibited the same insulin sensitivity as CHO-HIR with respect to 2-deoxyglucose uptake. However, the dose-response curve of insulin-stimulated thymidine incorporation in CHO-F/Y CT2 was shifted to the left (approximately 5-7-fold) compared with that in CHO HIR. There was no significant difference in insulin-like growth factor 1 stimulated thymidine incorporation between CHO-F/Y CT2 and CHO-HIR. Furthermore, the dose-response curve of insulin-stimulated kinase activity toward myelin basic protein in CHO-F/Y CT2 was also shifted to the left (approximately 5-fold) compared with that in CHO-HIR. Kinase assays in myelin basic protein-containing gels revealed that both species of MAP kinases (M(r) 44,000, 42,000) were more sensitive to activation by insulin in CHO-F/Y CT2 than in CHO-HIR. This observation was confirmed in immune complex kinase assays toward microtubule associated protein 2 (MAP2) using specific antibodies against mitogen-activated protein (MAP) kinase. R/K 1018 mutant insulin receptors showed an absence of insulin-stimulated kinase activity and CHO cells transfected with R/K 1018 (CHO R/K 1018) failed to enhance 2-deoxyglucose uptake or thymidine incorporation in response to insulin. In addition, R/K 1018 kinase-defective insulin receptors were unable to mediate insulin-stimulated MAP kinase activation. These data suggest that: 1) tyrosine kinase activity of the insulin receptor is required for activation of insulin-stimulated MAP kinases and 2) phosphorylation of COOH terminal tyrosine residues may play an inhibitory role in mitogenic signaling through regulation of MAP kinases. PMID- 1618781 TI - Depletion of poly(ADP-ribose) polymerase by antisense RNA expression results in a delay in DNA strand break rejoining. AB - The effects of inducible expression of poly(ADP-ribose) polymerase (PADPRP) antisense RNA in HeLa cells were determined in order to gain further insight into the biological roles of the poly(ADP-ribosyl)ation modification of nuclear proteins. A recombinant expression plasmid was prepared with the mouse mammary tumor virus (MMTV) promoter upstream of the antisense-oriented PADPRP cDNA. Expression of the antisense RNA was under strict control, with negligible effects on cell growth being apparent in the absence of inducer. Consistent with the previously described stability of PADPRP (half-life of at least 2 days, in vivo), 48-72 h were required after induction of antisense RNA expression by dexamethasone for the abundant concentration of PADPRP, normally present in HeLa cells, to be reduced by greater than 80%. The depletion of endogenous PADPRP as mediated by induced antisense RNA expression was established by: (i) a progressive synthesis of antisense transcripts in cells as assessed by Northern analysis; (ii) an 80% decrease in activity of the enzyme; and (iii) a greater than 90% reduction in the cellular content of PADPRP protein, as demonstrated by both immunoblotting and immunohistochemical analysis in intact cells. Several biological parameters were monitored in cells depleted of PADPRP. The chromatin of PADPRP-depleted cells was shown to have an altered structure as assessed by deoxyribonuclease I susceptibility. Cell morphology was also altered, with multinucleated aggregates being evident 72 h after induction of antisense RNA expression. Cells depleted of PADPRP were not able to commence DNA strand break joining of damaged DNA. However, DNA repair capacity was re-established at later time periods, indicating that PADPRP may contribute to alterations in chromatin structure that occur initially in DNA strand break rejoining and that the concentration of the enzyme in nuclei exceeds the requirement for DNA repair/replication. PMID- 1618782 TI - Structure of peptostreptococcal protein L and identification of a repeated immunoglobulin light chain-binding domain. AB - The gene for protein L, an immunoglobulin (Ig) light chain-binding protein expressed by some strains of the anaerobic bacterial species Peptostreptococcus magnus, was cloned and sequenced. The gene translates into a protein of 719 amino acid residues. Following a signal sequence of 18 amino acids and a NH2-terminal region ("A") of 79 residues, the molecule contains five homologous "B" repeats of 72-76 amino acids each. Further, toward the COOH terminus, two additional repeats ("C") were found. These are not related to the "B" repeats, but are highly homologous to each other. After the C repeats (52 amino acids each), a hydrophilic, proline-rich putative cell wall-spanning region ("W") was found, followed at the COOH-terminal end by a hydrophobic membrane anchor ("M"). Fragments of the gene were expressed, and the corresponding peptides were analyzed for Ig-binding activity. The B repeats were found to be responsible for the interaction with Ig light chains. An Escherichia coli high level expression system was adapted for the production of large amounts of two Ig-binding protein L fragments comprising one and four B repeats, respectively. PMID- 1618783 TI - Induction of myogenic differentiation by an expression vector encoding the DNA methyltransferase cDNA sequence in the antisense orientation. AB - To test the hypothesis that DNA methylation controls the state of differentiation of a mammalian cell, we transfected the stable mesenchymal line 10T1/2 with an expression vector encoding sequences from the DNA methyltransferase (DNA MeTase) cDNA in the antisense orientation. 10T1/2 cells transfected with the antisense construct (pZ alpha M), but not with the vector alone, exhibit morphological changes, convert into multinucleated tubular cells, and express the skeletal myosin heavy chain protein. The conversion to myogenic phenotype is a late event and is dependent on the number of replication events that the cell has undergone, suggesting that induction of myogenesis is a multistep process. Demethylation of sequences that are not involved in the myogenic process is detected at early passages, while demethylation and expression of the MyoD gene is a late event. This report establishes for the first time that demethylation is a very early event in commitment to myogenic differentiation, while demethylation and expression of MyoD is a late event. We suggest that other genes serve as the initial targets for demethylation and commitment of mesenchymal cells to myogenesis. The cell lines described in this report can serve as an important system for identifying these genes. PMID- 1618784 TI - Chicken vinculin and meta-vinculin are derived from a single gene by alternative splicing of a 207-base pair exon unique to meta-vinculin. AB - meta-Vinculin and vinculin are closely related proteins that are cytoplasmic components of microfilament-associated cell junctions. This report describes the structural relationship between these two proteins and the genetic basis for tissue-specific expression of meta-vinculin. Analysis of genomic DNA coding for amino acids 676-1066 of vinculin revealed 9 exons spanning an 11.7-kilobase pair region of the genome. In the 4 kilobase pairs of intervening sequence that separates vinculin exons E896-E915 and E916-E984, there is an open reading frame that predicts a sequence homologous to the 68-amino acid peptide specific to porcine meta-vinculin (Gimona, M., Small, J. V., Moeremans, M., Van Damme, J., Puype, M., and Van-dekerckhove, J. (1988) EMBO J. 7, 2329-2334). Analysis of the corresponding cDNA established that chicken meta-vinculin contains a 69-amino acid insertion between residues 915 and 916 of vinculin and that there are no other amino acid sequence differences between chicken vinculin and meta-vinculin. Muscle-specific expression of meta-vinculin occurs by alternative splicing of a transcript produced from a single gene because: all 20 genomic isolates that contain the 3' vinculin exons, also contain the meta-vinculin-specific exon; Southern blots performed at high stringency with exon-specific probes indicate the presence of a single gene; and the 3'-untranslated sequences of vinculin and meta-vinculin cDNAs are identical. PMID- 1618785 TI - Efficient plasma membrane expression of a functional platelet glycoprotein Ib-IX complex requires the presence of its three subunits. AB - The glycoprotein (GP) Ib-IX complex of the platelet plasma membrane mediates the adhesion of platelets to damaged blood vessel wall. The complex is composed of three membrane-spanning polypeptides, GP Ib alpha, GP Ib beta, and GP IX, all of which are absent from the platelets of patients with the hereditary bleeding disorder Bernard-Soulier syndrome. In this study we report stable expression of the recombinant receptor in three cell lines and demonstrate that the three subunits of the complex are necessary for its efficient expression on the plasma membrane. The expressed complex associates with the cytoskeleton of the transfected cells through an interaction with actin-binding protein and binds its ligand, von Willebrand factor. These data suggest that the lack of plasma membrane GP Ib-IX complex in the Bernard-Soulier syndrome could potentially arise from mutations affecting any one of its three subunits. PMID- 1618786 TI - Protein targeting across the three membranes of the Euglena chloroplast envelope. AB - A system has been developed for the import in vitro of precursor proteins into Euglena chloroplasts, which have three envelope membranes. Preparation of functional chloroplasts with intact envelope membranes has been optimized. Import of the precursor (50 kDa) for the tetrapyrrole biosynthesis enzyme porphobilinogen deaminase (PBGD), and processing to the mature size (40 kDa), occurred at 25 degrees C in the light and the presence of ATP, with an estimated efficiency of 62%. Pretreatment of the chloroplasts with proteases abolished this import, suggesting the involvement of specific protein receptors. The presequence of PBGD was found to be cleaved by Escherichia coli leader peptidase to an intermediate form (46 kDa). A construct in which the first 30 residues of the presequence (presumed to be the region removed by leader peptidase) had been deleted was no longer imported. Neither prePBGD nor the truncated precursor were imported into pea chloroplasts, although both bound to the pea chloroplast envelope. Conversely, a chimeric construct, in which the mature PBGD protein was fused downstream of the transit peptide for pea ferredoxin-NADP reductase, was efficiently imported into pea chloroplasts and processed to the mature size. However, this was not imported into Euglena chloroplasts, although again it bound to them. These results provide preliminary evidence for the possibility of two functional domains within the Euglena PBGD presequence. The implications of these findings with respect to the evolution of Euglena chloroplasts are discussed. PMID- 1618787 TI - Expression of four protein kinase C isoforms in rat fibroblasts. Distinct subcellular distribution and regulation by calcium and phorbol esters. AB - Protein kinase C (PKC), the major receptor for tumor-promoting phorbol esters, consists of a family of at least eight distinct lipid-regulated enzymes. How the various PKC isozymes are regulated in vivo and how they couple to particular cellular responses is largely unknown. We have examined the expression and regulation of PKC isoforms in R6 rat embryo fibroblasts. Northern and Western blot analyses indicate that these cells express four PKC isoforms, cPKC alpha, nPKC epsilon, nPKC delta, and nPKC zeta; of which nPKC epsilon and nPKC delta are the most abundant. In agreement with the simultaneous presence of cPKC and nPKC isozymes, both Ca(2+)-dependent and -independent PKC activities were detected in extracts of these cells. cPKC alpha and nPKC zeta were predominantly localized in the cytosol when subcellular fractionation was carried out in the presence of [ethylenebis(oxyethylenenitrilo)]tetraacetic acid. When cell lysis was carried out in the presence of Ca2+, greater than 50% of cPKC alpha redistributed to the particulate fraction, whereas nPKC zeta remained in the cytosol. In contrast to cPKC alpha and nPKC zeta, 60-80% of nPKC epsilon and nPKC delta were located in a Ca(2+)-insensitive, membrane-bound form. Treatment of R6 cells with 12-O tetradecanoyl phorbol 13-acetate (TPA), resulted in the translocation of all four PKC isozymes to the membrane fraction, and the subsequent down-regulation of cPKC alpha, nPKC zeta, and nPKC delta, nPKC epsilon, however, was only partially down regulated in response to long-term TPA exposure. Overproduction of exogenous cPKC beta I in R6 cells conferred partial resistance of nPKC delta to TPA-induced down regulation and potentiated the resistance of nPKC epsilon to down-regulation. These results demonstrate that the multiple isoforms of PKC which coexist within a single cell type are differentially regulated by extra- and intracellular stimuli and may thereby influence growth control and transformation via distinct mechanisms. PMID- 1618788 TI - Expression of four protein kinase C isoforms in rat fibroblasts. Differential alterations in ras-, src-, and fos-transformed cells. AB - In the accompanying study (Borner, C.B., Guadagno, S. N., and Weinstein, I. B. (1992) J. Biol. Chem. 267, 12892-12899) we found that R6 embryo fibroblasts express four isoforms of PKC, cPKC alpha, nPKC epsilon, nPKC delta, and nPKC zeta whose subcellular distribution, activation, and down-regulation are differentially regulated. Furthermore, we demonstrated that overproduction of an exogenous cPKC beta I isoform in these cells (R6-PKC3) altered the TPA-induced down-regulation of nPKC delta and nPKC epsilon. In this paper we show that transformation of R6 or R6-PKC3 cells with a variety of different oncogenes results in differential alterations in expression of individual PKC isoforms. R6 or R6-PKC3 cells transformed by an activated c-H-ras oncogene displayed a marked increase in the expression of both cPKC alpha and nPKC delta, decreased expression of nPKC epsilon, and no change in the expression of nPKC zeta. These alterations occurred at both the mRNA and protein levels but did not significantly affect the subcellular distribution of any of the four isoforms. Studies using actinomycin D and nuclear run-off assays indicated that the increased expression of cPKC alpha in ras-transformed cells was due to increased de novo transcription rather than increased mRNA stability. Qualitatively similar, but less extensive changes in the expression of the four PKC isoforms were seen in v-fos-transformed R6-PKC3 cells. Decreased expression of nPKC epsilon was also seen in the v-src-transformed R6- and R6-PKC3 lines; however, the cellular level of cPKC beta I appeared to be a limiting factor in mediating the effects of v-src on the increased expression of cPKC alpha and nPKC delta. Interestingly, no major changes in the levels of expression of any of the four PKC isoforms were found when R6 cells were transformed by myc, neu/erb-B2, or mos oncogenes. These results demonstrate that transformation of R6 cells by the oncogenes ras, src, and fos differentially alter the expression of three isoforms of PKC in the same host cell, and they suggest that individual isoforms may play distinct roles in mediating cellular transformation by specific oncogenes. PMID- 1618789 TI - Molecular cloning and analysis of an eIF-4A-related rat liver nuclear protein. AB - In this paper, we report the cloning and analysis of a cDNA encoding a protein of M(r) congruent to 47,000 (p47), which is localized to the nucleus of rat hepatocytes. The cDNA showed 37% overall sequence identity with a mouse translation initiation factor, eIF-4A, which belongs to a family of putative ATP dependent RNA helicases. We raised polyclonal antibodies against the fusion protein and by indirect immunofluorescence on primary cultures of hepatocytes have demonstrated that p47 is located in the nucleus. Although only approximately 27% of hepatocytes showed this nuclear staining, most of the nuclei in proliferating transformed cell lines such as 3T3, PtK-1, and Hela were fluorescently labeled. Studies on serum-starved cells in culture indicated that p47 was expressed in a cell cycle-dependent manner. Northern analyses demonstrated that the levels of p47 mRNA were high in fetal liver and dropped significantly after birth to low levels in adult liver. Our data suggest that p47 is developmentally regulated in rat liver at the mRNA level. PMID- 1618790 TI - Heat shock protein 27 and alpha B-crystallin can form a complex, which dissociates by heat shock. AB - We have previously demonstrated that in non-oncogenic adenovirus-transformed baby rat kidney cells a complex of hsp27 and a 22-kDa protein is present, which is lacking in oncogenic cells (Zantema, A., de Jong, E., Lardenoije, R., and van der Eb, A. J. (1989) J. Virol. 63, 3368-3375). Here we show that the 22-kDa protein is identical to alpha B-crystallin. The complex of hsp27 and alpha B-crystallin is also found in some other (non-transformed) cells. However, in most cells tested only hsp27 and no alpha B-crystallin is synthesized. Gel filtration studies show that both proteins are present almost exclusively in a 700-kDa complex. Heat treatment makes the complex fall apart, which is accompanied by a change in the conformation of alpha B-crystallin. Upon recovery, complexes are formed again from both pre-existing and newly synthesized proteins. PMID- 1618791 TI - Sequence and specificity of a soluble lactose-binding lectin from Xenopus laevis skin. AB - A 16-kDa lactose-binding lectin comprises 5% or more of the soluble protein in Xenopus laevis skin. This lectin is mainly localized in the cytoplasm of granular gland cells. In response to stress, the lectin along with a variety of toxic and antibiotic peptides are released onto the skin surface by holocrine secretion. We have purified the lectin, sequenced tryptic peptides using tandem mass spectrometry and Edman degradation, and isolated full-length cDNA using a deduced oligonucleotide. Comparison of the cDNA and peptide sequences revealed expression of at least two isolectins, which differ in sequence at only two or three amino acids. Comparison of cDNA with complementary message by ribonuclease protection confirmed expression in approximately equal abundance of two nearly identical messages. The major soluble lactose-binding lectin expressed in Xenopus muscle is composed of these same isolectins, but at 100-fold lower levels. Similarities and distinctions in sequence and carbohydrate-binding specificity indicate that this lectin is a novel member of a family of soluble lactose-binding lectins expressed in a wide range of vertebrate tissues. PMID- 1618792 TI - A deletion in the ornithine aminotransferase gene in gyrate atrophy. AB - Gyrate atrophy (GA) is an autosomal recessive chorioretinal degenerative disease of the eye caused by an inborn defect of the nuclear encoded mitochondrial enzyme ornithine aminotransferase (OAT). We have described previously a GA patient with a 5.0-kilobase pair truncated EcoRI OAT gene fragment and the absence of OAT mRNA on Northern blot analysis. Cloning and sequencing analysis of the truncated gene fragment revealed a 1,072-base pair (bp) deletion including the entire exon 6, starting in intron 5, 172 bp upstream of exon 6 and ending in intron 6, 772 bp downstream of exon 6. A short direct repeat sequence (AGGAGC), resembling the sequence shown to cause DNA polymerase alpha to pause, and sequences capable of forming hairpin loops were both present at the 5' and 3' break-points of the deletion. Reverse transcription-polymerase chain reaction amplification of the patient's RNA with OAT primers yielded DNA fragments of two different sizes, consistent with a low level expression of OAT mRNA. Direct sequencing of the smaller fragment demonstrated the complete absence of exon 6 sequence in the mRNA predicted from the deletion, causing a reading frame shift which results in a premature termination codon at position 192. The mutation in the other allele has been demonstrated by polymerase chain reaction, denaturing gradient gel electrophoresis, and direct sequencing also to be a premature termination codon in exon 6. The absence of detectable OAT mRNA in this patient is consistent with these premature termination mutations because they have been shown to decrease the level of mRNA, especially if present early in the coding sequence. PMID- 1618793 TI - Release and recycling of eukaryotic initiation factor 2 in the formation of an 80 S ribosomal polypeptide chain initiation complex. AB - The eukaryotic initiation factor (eIF)-5 mediates hydrolysis of GTP bound to the 40 S initiation complex in the absence of 60 S ribosomal subunits. The eIF-2.GDP formed under these conditions is released from the 40 S ribosomal subunit while initiator Met-tRNA(f) remains bound. The released eIF-2.GDP can participate in an eIF-2B-catalyzed GDP/GTP exchange reaction to reform the Met-tRNA(f).eIF-2.GTP ternary complex. In contrast, when 60 S ribosomal subunits were also present in an eIF-5-catalyzed reaction, the eIF-2.GDP produced remained bound to the 60 S ribosomal subunit of the 80 S initiation complex. When such an 80 S initiation complex, containing bound eIF-2.GDP, was incubated with GTP and eIF-2B, GDP was released. However, eIF-2 still remained bound to the ribosomes and was unable to form a Met-tRNA(f)l.eIF-2.GTP ternary complex. In contrast, when 60 S ribosomal subunits were preincubated with either free eIF-2 or with eIF-2.eIF-2B complex and then added to a reaction containing both the 40 S initiation complex and eIF 5, the eIF-2.GDP produced did not bind to the 60 S ribosomal subunits but was released from the ribosomes. Thus, the 80 S initiation complex formed under these conditions did not contain bound eIF-2.GDP. Under similar experimental conditions, preincubation of 60 S ribosomal subunits with purified eIF-2B (free of eIF-2) failed to cause release of eIF-2.GDP from the ribosomal initiation complex. These results suggest that 60 S ribosome-bound eIF-2.GDP does not act as a direct substrate for eIF-2B-mediated release of eIF-2 from ribosomes. Rather, the affinity of 60 S ribosomal subunits for either eIF-2, or the eIF-2 moiety of the eIF-2.eIF-2B complex, prevents association of 60 S ribosomal subunits with eIF-2.GDP formed in the initiation reaction. This ensures release of eIF-2 from ribosomes following hydrolysis of GTP bound to the 40 S initiation complex. PMID- 1618794 TI - Structural characterization of a novel cholinergic neuron-specific ganglioside in bovine brain. AB - A new ganglioside antigen, termed Chol-1 alpha-b, recognized by cholinergic neuron-specific antibody, Chol-1 alpha, was isolated from bovine brain ganglioside mixture using Q-Sepharose. The yield was approximately 1.3 mg from 5 g of the total ganglioside. The chemical structure was characterized as a novel ganglioside by means of gas-liquid chromatography, a permethylation study, mild acid hydrolysis, thin layer chromatography-enzyme immunostaining, fast atom bombardment mass spectrometry, and proton nuclear magnetic resonance spectroscopy. The ganglioside has the following unique structure. [formula: see text] When examined by thin layer chromatography immunostaining and enzyme-linked immunosorbant assays, this ganglioside has the most intense immunoreactivity with Chol-1 alpha antibody among bovine brain gangliosides. As combined with our previous results (Hirabayashi, Y., Hyogo, A., Nakao, T., Tsuchiya, K., Suzuki, Y., Matsumoto, M., Kon, K., and Ando, S. (1990) J. Biol. Chem. 265, 8144-8151; Ando, S., Hirabayashi, Y., Kon, K., Inagaki, F., Tate, S., and Whittaker, X. (1992) J. Biochem. (Tokyo), 111, 287-290), the present study indicates the occurrence of a new series of gangliosides containing N-acetylneuraminic acid residue attaching to N-acetylgalactosamine as cholinergic specific antigens. PMID- 1618795 TI - Cardiac expressions of alpha- and beta-myosin heavy chains and sarcomeric alpha actins are regulated through transcriptional mechanisms. Results from nuclear run on assays in isolated rat cardiac nuclei. AB - In the heart, mRNA accumulations for sarcomeric actins and myosin heavy chains (MHC) are subject to diverse regulatorial processes. To study cardiac contractile protein transcriptional regulations, an in vitro transcription system using nonenzymatically isolated rat cardiac nuclei was characterized. Transcription was shown to be rapid and continuous during the first 20 min of incubation and 5.4 fold less than that seen from comparably isolated hepatocyte nuclei. Neither RNase nor DNase activities were detectable. Direct transcriptional analyses of the alpha- and beta-MHC and cardiac and skeletal alpha-actin genes from cardiac nuclei were performed. In 23-24-day-old rats, significant levels of transcription were seen for alpha-MHC and for the sarcomeric alpha-actins. beta-MHC was just detectable, and no positive signals were ever seen for fibronectin. We then compared the perecentages of MHC and sarcomeric alpha-actin expressions determined from 1) the transcriptional assays and 2) total isolated RNA (alpha MHC: 90.1 +/- 4.8% (transcription), 93.0 +/- 4.7% (accumulation); beta-MHC: 9.9 +/- 4.8%, 7.0 +/- 4.7%; cardiac alpha-actin: 84.0 +/- 2.5%, 84.9 +/- 2.5%; skeletal alpha-actin: 16.1 +/- 2.5%, 15.0 +/- 2.5%). The results support the conclusion that the primary mechanisms controlling the accumulations of these gene products are transcriptional. Additionally, we show that an anti-sense mRNA showing strong homology or identity with the 5' end of the beta-MHC gene is transcribed in cardiac nuclei but not in hepatocyte nuclei. PMID- 1618796 TI - Four conserved cysteine residues are required for the DNA binding activity of nuclear factor I. AB - The role of Cys residues in the site-specific DNA binding activity of the nuclear factor I (NFI) family of proteins was assessed by chemical modification and site specific mutagenesis. Treatment with the thio-specific reagent N-ethylmaleimide abolished site-specific DNA binding of all forms of NFI present in HeLa nuclear extracts. Preincubation of cell extracts with an oligonucleotide containing an NFI-binding site provided partial protection of NFI from N-ethylmaleimide inactivation. Mutations were made in the cDNA encoding a truncated form of the NFI-C/CAAT box transcription factor-1 protein, converting each of the five Cys residues in the DNA-binding domain of the protein into Ser residues. NFI-C proteins containing mutations in any of four conserved Cys residues, expressed in Escherichia coli or in vitro, did not bind to DNA. NFI-C with a mutation in a nonconserved Cys residue had normal DNA binding activity. Both this active mutant and wild-type NFI-C protein were inactivated by modification of their sulfhydryl residues with 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), and preincubation with an oligonucleotide containing an NFI-binding site gave partial protection against inactivation. After modification with DTNB, DNA binding activity was partially restored by subsequent incubation with dithiothreitol, indicating that inactivation of NFI by DTNB was reversible. These studies indicate an essential role for free sulfhydryl residues in NFI-DNA binding. PMID- 1618797 TI - Pro-opiomelanocortin synthesized by corticotrophs bears asparagine-linked oligosaccharides terminating with SO4-4GalNAc beta 1,4GlcNAc beta 1,2Man alpha. AB - We have determined that greater than or equal to 80% of the Asn-linked oligosaccharides on the glycosylated form of mouse adrenocorticotropin (15-kDa adrenocorticotropin (ACTH)) bear one or more branches terminating with the sequence SO4-4GalNAc beta 1,4GlcNAc beta 1,2Man alpha (S4GGnM). Proopiomelanocortin (POMC), the precursor of ACTH, is the first example of a glycoprotein that is not a member of the glycoprotein hormone family to bear such sulfated structures. Like lutropin and thyrotropin, 15-kDa ACTH bears dibranched oligosaccharides terminating with SO4-4-GalNAc; however, at least half of the oligosaccharides on 15-kDa ACTH terminating with SO4-4-GalNAc consist of more highly branched structures that have not previously been described. Both the GalNAc beta 1,4GlcNAc beta 1,2Man-4-sulfotransferase and the glycoprotein hormone specific GalNAc-transferase are expressed in the corticotroph-derived AtT-20 cell line. A tripeptide recognition sequence, Pro-Val-Lys, similar to the Pro-Leu-Arg sequence required for recognition of glycoprotein hormone alpha- and beta subunits by the glycoprotein hormone-specific GalNAc-transferase, is present 8 residues amino-terminal to the glycosylated Asn of 15-kDa ACTH. Thus, POMC has the features expected for specific addition of the S4GGnM sequence to its oligosaccharides. The recent discovery of a receptor in hepatic endothelial cells that recognizes oligosaccharides terminating with S4GGnM suggests these sulfated oligosaccharides will regulate the circulatory half-life of glycosylated POMC cleavage products. PMID- 1618798 TI - The human gene for renin-binding protein. AB - The human renin-binding protein (RnBP) gene was isolated from a human placental genomic library and characterized. The gene spans about 10 kilobases and consists of 11 exons separated by 10 introns. The 5'-flanking region and the exon-intron boundaries were sequenced. Residue G* in 5'-CGAG*TGG-3' was identified as the major transcription initiation site, and "GC" boxes were found in the vicinity of the cap site. No typical "TATA" or "CCAAT" box exists in the 5'-flanking region. The hydrophobic domain followed by a leucine-zipper motif in RnBP is encoded by the sixth exon. A fragment of the human RnBP gene (nucleotides -739 to +244) linked to the chloramphenicol acetyltransferase gene was transfected into human Wilms' tumor G401 and mouse L929 cells. The expression of this chimeric gene in G401 cells was 4-fold higher than that in L929 cells, the tissue-specific regulation of RnBP gene expression thus being suggested. The promoter for the RnBP gene was shown to be localized in nucleotides -35 to +244 on assaying of the promoter activity using deletion mutants of the chimeric constructs. The RnBP gene was found to be located in human chromosome X by means of polymerase chain reaction of hybrid DNAs from human and hamster somatic cells. PMID- 1618799 TI - Thyroid hormone receptor mutants that cause resistance to thyroid hormone. Evidence for receptor competition for DNA sequences in target genes. AB - Several distinct mutations in the ligand-binding domain of the beta form of the thyroid hormone receptor have been reported in kindreds with the autosomal dominant syndrome of generalized resistance to thyroid hormone (GRTH). GRTH receptor mutants are functionally inactive but capable of inhibiting normal receptor function in transient expression studies. We examined the possibility that this dominant negative activity of the GRTH mutants involves competition for receptor binding to DNA. Mutations introduced into either the T3 ligand-binding domain (LBD) or into the DNA-binding domain (DBD) of the receptor eliminated the transcriptional activity of the receptor. In cotransfection experiments, the LBD mutants, but not the DBD mutants, inhibited the transcriptional activity of the normal receptor. The inhibitory activity of the LBD mutants was abolished by the introduction of an additional mutation into the DBD, suggesting that the DBD is required for dominant negative activity. A chimeric receptor, in which the DNA binding domain of the thyroid hormone receptor was exchanged with the homologous region in the glucocorticoid receptor (GTG), was used to study thyroid hormone receptor competition for GTG interactions with thyroid receptor target sequences. In the absence of thyroid hormone, the normal thyroid hormone receptor inhibited dexamethasone stimulated transcription by GTG. The transcriptional activity of GTG was also inhibited by the LBD mutants but not by a DBD mutant of the thyroid hormone receptor. These results indicate that the thyroid hormone receptor mutations that occur in GRTH compete with normal receptors at DNA-binding sites in target genes to block normal receptor function. PMID- 1618800 TI - Evidence that mutations in a loop region of the alpha-subunit inhibit the transition from an open to a closed conformation in the tryptophan synthase bienzyme complex. AB - Rapid-scanning stopped-flow (RSSF) UV-visible spectroscopy has been used to investigate the effects of single amino acid mutations in the alpha-subunit of the Salmonella typhimurium tryptophan synthase bienzyme complex on the reactivity at the beta-subunit active site located 25 to 30 A distant. The pyridoxal 5' phosphate (PLP) cofactor provides a convenient spectroscopic probe to directly monitor catalytic events at the beta-active site. Single substitutions of Phe for Glu at position 49, Leu for Gly at position 51, or Tyr for Asp at position 60 in the alpha-subunit strongly alter the observed steady state and pre-steady state inhibitory effects of the alpha-subunit-specific ligand alpha-glycerophosphate (GP) on the PLP-dependent beta-reaction. However, similar GP-induced allosteric effects on the distribution of covalent intermediates bound at the beta-site that are observed with the wild-type enzyme (Houben, K.F., and Dunn, M.F. (1990) Biochemistry 29, 2421-2429) also are observed for each of the mutant bienzyme complexes. These results support the hypothesis that the preferred pathway of indole from solution into the beta-site is via the alpha-site and the interconnecting tunnel (Dunn, M.F., Aguilar, V., Brzovic, P., Drewe, W.F., Houben, K.F., Leja, C.A., and Roy, M. (1990) Biochemistry 29, 8598-8607). Residues alpha E49, alpha G51, and alpha D60 are part of a highly conserved inserted sequence in the alpha/beta-barrel topology of the alpha-subunit. We propose that the GP-induced inhibition of the beta-reaction results, in part, from a ligand-dependent conformational change from an "open" to a "closed" structure of the alpha-subunit which involves this region of the alpha-subunit and serves to obstruct the direct access of indole into the tunnel. Our findings suggest that the altered kinetic behavior observed for the alpha-mutants in the presence of GP reflects an impaired ability of the modified bienzyme complex to undergo the conformational transition from the open to the closed form. PMID- 1618801 TI - The amino terminus of ADP-ribosylation factor (ARF) is a critical determinant of ARF activities and is a potent and specific inhibitor of protein transport. AB - Deletion of the amino-terminal 17 residues from human ADP-ribosylation factor (ARF) resulted in a protein ([delta 1-17]mARF1p) devoid of ARF activity but which retained the ability to bind guanine nucleotides with high affinity. Unlike the wild type, the binding of guanine nucleotides to this deletion mutant was found to be independent of added phospholipids. A chimeric protein was produced, consisting of 10% (the amino-terminal 17 amino acids) human ARF1p and 90% ARL1p, an ARF-like protein (55% identical protein sequence) from Drosophila. This chimera was found to have ARF activity, lacking in the parental ARL1 protein. Thus, the amino terminus of ARF1p was shown to be a critical component of ARF activity. A synthetic peptide, derived from the amino terminus of ARF1p, has no ARF activity. Rather, the peptide was found to be a specific inhibitor of ARF activities. This peptide was also found to be a potent and specific inhibitor of both an in vitro intra-Golgi transport assay and the guanosine 5'-3-O (thio)triphosphate-stimulated accumulation of coated vesicles and buds from Golgi preparations. We conclude that ARF is required for the budding of coated vesicles from the Golgi stacks and serves a regulatory role in protein secretion through the Golgi in eukaryotic cells. PMID- 1618802 TI - Evidence for ADP-ribosylation factor (ARF) as a regulator of in vitro endosome endosome fusion. AB - We have used an in vitro endosome fusion assay, recombinant ARF, synthetic peptides, and guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) to study the role of ARF during endocytosis. Previous work has shown that GTP gamma S stimulates in vitro endosome fusion in dilute cytosol (less than 0.5 mg/ml) but inhibits fusion in concentrated cytosol (greater than 1.0 mg/ml). Two peptides corresponding to the NH2-terminal 16 amino acids of human ARF1 and ARF4 blocked GTP gamma S stimulation of fusion in dilute cytosol and reversed GTP gamma S inhibition of fusion in concentrated cytosol. The addition of recombinant human ARF1 to endosomes in dilute or concentrated cytosol resulted in GTP gamma S-dependent inhibition of fusion. Only the myristoylated form of ARF inhibited fusion. The NH2-terminal ARF1 peptide reversed inhibition by recombinant ARF1. Preincubation experiments showed that endosomes could form an ARF-resistant intermediate during the fusion process. Western blot analysis revealed clathrin-coated vesicles extracted with detergent retained ARF. The results suggest that ARF is involved in both the stimulatory and inhibitory effects of GTP gamma S in dilute and concentrated cytosol, respectively. Furthermore, myristoylation, the NH2-terminal domain, and binding to GTP appear to be critical for ARF activity during an early prefusion step required for endocytosis. PMID- 1618803 TI - ADP-ribosylation factor is required for vesicular trafficking between the endoplasmic reticulum and the cis-Golgi compartment. AB - We describe the potential role of ADP-ribosylation factor (ARF) in vesicular trafficking using an in vitro assay that efficiently reconstitutes transport between the endoplasmic reticulum (ER) and the cis-Golgi compartment in mammalian semi-intact cells, a population of cells in which the plasma membrane is physically perforated to reveal intact ER and Golgi compartments. We demonstrate that peptides identical to the amino-terminal domain of ARF, which inhibit ARF cofactor activity in cholera toxin-catalyzed ADP-ribosylation of G alpha S (Kahn, R. A., Randazzo, P., Serafini, T., Weiss, O., Rulka, C., Clark, J., Amherdt, M., Roller, P., Orci, L., and Rothman, J. E. (1992) J. Biol. Chem. 267, 13039-13046), inhibit transport of the vesicular stomatitis virus G protein between the ER and cis-Golgi compartment. Inhibition of transport was rapid (t1/2 = 30-60 s) and irreversible. Half-maximal inhibition was observed at concentrations of 15 and 22 microM with peptides identical to the amino-terminal domain of the human ARF4 (hARF4) protein and the human ARF1 protein, respectively. Kinetic analysis of vesicular stomatitis virus G protein transport suggested that the hARF4 peptide inhibits a late vesicle fusion step. In addition, incubation of semi-intact cells in the presence of the myristoylated form human ARF1 (hARF1myr) protein, but not the nonmyristoylated form of ARF1, inhibited transport. In contrast to peptide, the hARF1myr blocked an early transport step, similar to that observed with guanosine 5'-3-O-(thio)triphosphate. These results suggest that ARF and components facilitating ARF function play an important role in the cyclical fission and fusion of transport vesicles mediating ER to Golgi trafficking. PMID- 1618804 TI - A common sequence motif, -E-G-Y-A-T-A-, identified within the primase domains of plasmid-encoded I- and P-type DNA primases and the alpha protein of the Escherichia coli satellite phage P4. AB - DNA primases encoded by the conjugative plasmids ColIb-P9 (IncI1), RP4, and R751 (IncP), and the protein of the Escherichia coli satellite phage P4 alpha were shown to contain a common amino acid sequence motif -E-G-Y-A-T-A-. The P4 alpha gene product, required for initiation of phage DNA replication, exhibits primase activity on single-stranded circular DNA templates. This priming activity resembles the enzymatic activity of DNA primases encoded by conjugative plasmids in terms of template utilization and the ability to synthesize primers that can be elongated by DNA polymerase III holoenzyme. The -E-G-Y-A-T-A- motif is part of an extended sequence region most conserved within the primase domains of the four enzymes. Single amino acid substitutions generated in the -E-G-Y-A-T-A- motif of the RP4 TraC2 and the P4 alpha protein affect priming activity, supporting the hypothesis that the conserved sequence motif is part of the active center for primase function. A mutation that eliminates priming activity causes P4 phage to grow poorly and to depend upon the host dnaG primase. Computer analysis identified two additional sequence motifs within the amino acid sequence of the P4 alpha protein: a potential zinc-finger motif and a "type A" nucleotide binding site, both strikingly similar to sequence motifs described in various DNA primases and helicases. PMID- 1618805 TI - The epithelin precursor encodes two proteins with opposing activities on epithelial cell growth. AB - Epithelin 1 and 2 were originally purified from rat kidneys based on their ability to inhibit the growth of A-431 human epidermoid carcinoma cells (Shoyab, M., McDonald, V.L., Byles, C., Todaro, G.J., and Plowman, G.D. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 7912-7916). This study presents the complete amino acid sequence of these two growth factors and the cloning of their cDNA from rat, mouse, and human sources. Epithelins 1 and 2 are 56- and 57-amino acid polypeptides, respectively, and share 47% amino acid sequence identity with the conserved spacing of 12 cysteine residues. Molecular cloning revealed that both proteins are encoded by a single precursor that contains 7 1/2 copies of this novel 12-cysteine motif, 2 of which represent the known active molecules. Recombinant expression in COS cells demonstrated that the epithelin 1 protein was mitogenic on rodent keratinocytes and fibroblasts. In contrast, epithelin 2 had no activity on these cells, but at high concentrations was capable of antagonizing the growth proliferative activities of epithelin 1. Northern analysis shows the epithelin mRNA to be expressed in many types of epithelial cells. The broad expression profile of epithelin transcripts, along with the opposing activities of the two mature protein products, implicates these factors as natural mediators of epithelial homeostasis. PMID- 1618806 TI - An actin footprint on villin. Single site substitutions in a cluster of basic residues inhibit the actin severing but not capping activity of villin. AB - Villin is a multidomain protein that severs, caps, and bundles actin filaments. We employed a chemical modification/cleavage strategy to identify residues whose chemical reactivities are reduced when villin is complexed with actin. We found that actin protects 3 methionine residues, Met125, Met379, and Met711 from oxidation by N-chlorosuccinimide. Because Met125 lies within the actin-severing domain of villin (44T), we probed this region for actin binding sites using a series of overlapping peptides each with an additional cysteine residue at their C terminus. Each peptide, as a disulfide-bonded dimer, was examined for actin cross-linking activity by electron microscopy and light scattering. Our results with M3R suggest this region contains an F-actin binding site and are consistent with proteolysis and deletion mutagenesis studies of gelsolin. Single substitution of the basic residues modulated actin severing but not capping activity of 44T. Circular dichroism and protease digestions did not detect alterations in secondary structure or conformational changes in the mutants, although some are cleaved more rapidly, thereby suggesting a change in the packing of the domains. Our results highlight that basic residues comprise part of the F-actin binding site that is involved in the actin severing activity of villin. PMID- 1618807 TI - Redesigned purification yields a fully functional PutA protein dimer from Escherichia coli. AB - Proline utilization by Escherichia coli and Salmonella typhimurium requires expression of genes putP (encoding a proline transporter) and putA. Genetic data indicate that the PutA protein is both put repressor and a respiratory chain linked dehydrogenase. We report a redesigned purification procedure as well as the physical characteristics and biological activities of the PutA protein purified from E. coli. The purified protein was homogeneous as determined by electrophoresis performed under denaturing and nondenaturing conditions. Its N terminal sequence corresponded to that predicted by the DNA sequence. We showed copurification of proline and delta 1-pyrroline-5-carboxylate dehydrogenase activities. Purified PutA protein bound put DNA in vitro in an electrophoretic band-shift assay and it could be reconstituted to inverted membrane vesicles, yielding proline dehydrogenase activity. The Stokes radius and Svedberg coefficient of the protein were determined to be 7.1 nm and 9.9 S, respectively. These hydrodynamic data revealed that the protein in our preparation was dimeric with a molecular mass of 293 kDa and that it had an irregular shape indicated by the friction factor (f/f0) of 1.6. PMID- 1618808 TI - A 13-amino acid n-terminal domain of a basic proline-rich protein is necessary for storage in secretory granules and facilitates exit from the endoplasmic reticulum. AB - We have investigated the role of different domains of a salivary basic proline rich protein in intracellular transport and sorting of proline-rich proteins to the secretory granules. We have cloned a full-length cDNA of a basic proline-rich protein from the rat parotid and expressed it in AtT-20 cells. It was correctly sorted into secretory granules as shown by EM immunolocalization and by its presence in 8-bromocyclic AMP-stimulated secretion. Deletion of the N-terminal thirteen amino acid domain upstream from the proline-rich domain eliminated storage whereas deletion of the C-terminal 20-amino acid domain downstream from the proline-rich domain had no effect. Intracellular transport of full-length and mutant proline-rich proteins was unusually slow due to slow exit from the endoplasmic reticulum. However, the rate of transport increased with increasing level of expression for the full-length protein and the C-terminal deletion mutant. In contrast, the rate of transport of the N-terminal deletion mutant was independent of the level of expression. These results imply that the N-terminal domain is necessary for both storage and efficient intracellular transport. Moreover, interactions (self-aggregation?) that mediate sorting may begin as early as the endoplasmic reticulum. PMID- 1618809 TI - Internalization of the human insulin receptor. The insulin-independent pathway. AB - Internalization of the human insulin receptor requires the activation by insulin of the intrinsic kinase of the receptor. However, even in the absence of kinase activation, insulin receptors slowly enter the cells. In the present study, we addressed the question of this insulin-independent pathway of internalization. To that end, we traced insulin receptor internalization with a monoclonal antibody (mAb 83-14) directed against the alpha-subunit of the human insulin receptor. Internalization of this antibody was followed in Chinese hamster ovary (CHO) cells transfected with either normal (CHO.HIRC2) or kinase-deficient (CHO.A1018) human insulin receptors. The internalization rate of 125I-mAb 83-14 was comparable in CHO cells expressing kinase-active or kinase-inactive receptors and was similar to that observed for 125I-insulin in CHO.A1018 cells. Moreover, in CHO.HIRC2 cells, the internalization of 125I-mAb 83-14 was identical with that of its 125I-Fab fragments. Thus, mAb 83-14 represents an appropriate tool to study the constitutive internalization of the insulin receptor. Internalization of insulin receptors tagged with 125I-mAb 83-14 was unaffected by cytochalasin B, which excluded a macropinocytotic process. By contrast, internalization was sensitive to hypertonia, which abrogates clathrin-coated pits-mediated endocytosis. The implication of clathrin-coated pits in this internalization process was directly demonstrated by quantitative electron microscopic autoradiography, which showed that 125I-mAb 83-14 present on the nonvillous domain of the cell surface preferentially associate with clathrin-coated pits at all time points. PMID- 1618810 TI - The signal for Golgi retention of bovine beta 1,4-galactosyltransferase is in the transmembrane domain. PMID- 1618811 TI - Cyclosporin A, the cyclophilin class of peptidylprolyl isomerases, and blockade of T cell signal transduction. AB - Cyclosporin A, the major immunosuppressive drug in transplantation, and the more potent therapeutic drug candidate, FK506, have led to the discovery of two superfamilies of immunosuppressant binding proteins, the cyclophilins and the FK binding proteins. These proteins, enzymes with high kcat values for isomerization of X-Pro bonds in peptides and protein substrates, are distributed in all cell compartments where protein folding normally occurs. It is likely that they play major roles in the protein folding and protein trafficking in the cell. It is also likely that they have been suborned in T cells by the immunosuppressant drugs that are potent pseudosubstrate ligands that selectively block the signal transduction cascade. The discovery of the inhibition of protein phosphatase 2B (calcineurin) by the drug-immunophilin complex (CsA-CyP or FK506-FKBP) provides evidence for a specific downstream target of the drug-immunophilin complexes and may prompt a search for endogenous ligands of cyclophilin and FKBP that may effect signal transduction regulation. The molecular insights gained over a short time in this area have been remarkable; they promise to elucidate the steps in T cell activation and delineate new targets for immunosuppressive therapy. PMID- 1618812 TI - Presequence binding factor-dependent and -independent import of proteins into mitochondria. AB - A cytosolic protein factor(s) is involved in the import of precursor proteins into mitochondria. PBF (presequence binding factor) is a protein factor which binds to the precursor form (pOTC) of rat ornithine carbamoyltransferase (OTC) but not to the mature OTC, and is required for the mitochondrial import of pOTC. The precursors for aspartate aminotransferase and malate dehydrogenase as well as pOTC synthesized in a reticulocyte lysate were efficiently imported into the mitochondria. However, the precursors synthesized in the lysate depleted for PBF by treatment with pOTC-Sepharose were not imported. Readdition of the purified PBF to the depleted lysate fully restored the import. pOTC synthesized in the untreated lysate sedimented as a complex with a broad peak of around 9 S, whereas pOTC synthesized in the PBF-depleted lysate sedimented at an expected position of monomer (2.5 S). When the purified PBF was readded to the depleted lysate, pOTC sedimented as a complex of about 7 S. In contrast to most mitochondrial proteins, rat 3-oxoacyl-CoA thiolase is synthesized with no cleavable presequence and an NH2-terminal portion of the mature protein functions as a mitochondrial import signal. The thiolase synthesized in the PBF-depleted lysate could be efficiently imported into the mitochondria, and readdition of PBF had little effect on the import. The thiolase synthesized in the untreated, the PBF-depleted, or the PBF readded lysate sedimented at an expected position of monomer (2.5 S). These observations provide support for the existence of PBF-dependent and -independent pathways of mitochondrial protein import. PMID- 1618813 TI - Expression of functional G protein beta gamma dimers of defined subunit composition using a baculovirus expression system. AB - The 36-kDa beta 1, 35-kDa beta 2, and 6.5-kDa gamma 2 subunits of the heterotrimeric guanine nucleotide-binding proteins have been overexpressed in Sf9 cells using a baculovirus expression system. The gamma 2 subunit expressed in Sf9 cells incorporated label derived from [3H]mevalonate and is therefore likely to be isoprenylated, as is its mammalian counterpart. Extracts of Sf9 cells doubly infected with viruses encoding a beta subunit and viruses encoding a gamma subunit are active in promoting the pertussis toxin-catalyzed ADP-ribosylation of a G protein alpha subunit. However, extracts from Sf9 cells singly infected with viruses encoding either a beta or gamma subunit are not active in this assay. Results demonstrate utility of the insect/baculovirus system for expressing G protein beta gamma subunits of defined composition. PMID- 1618814 TI - Insulin receptors are bivalent as demonstrated by photoaffinity labeling. AB - Insulin receptors in human placental membranes were photoaffinity-labeled with a radioactive human insulin-like growth factor I (hIGF-I) photoprobe N epsilon B28 monoazidobenzoyl 125I-hIGF-I either alone or together with a non-radioactive insulin photoprobe N epsilon B29-monoazidobenzoyl insulin. Precipitation of the solubilized receptors with anti-insulin antibody showed that receptors labeled with the radioactive hIGF-I photoprobe were detected in the immunoprecipitate only when photolabeling was carried out in the presence of the non-radioactive insulin photoprobe. Comparable results were obtained in converse experiments using a radioactive insulin photoprobe N epsilon B29-monoazidobenzoyl 125I insulin, a non-radioactive hIGF-I photoprobe N epsilon B28-monoazidobenzoyl hIGF I, and an antibody to hIGF-I. The amount of radioactive receptors precipitated by either the anti-insulin antibody or the anti-hIGHF-I antibody was close to the expected amount. These observations demonstrate that the insulin receptor is bivalent being capable of binding two molecules of ligand. PMID- 1618815 TI - Destabilization of ornithine decarboxylase by transfected antizyme gene expression in hepatoma tissue culture cells. AB - The degradation of ornithine decarboxylase (ODC) is stimulated by polyamines in a protein synthesis-dependent manner. It has been suggested that antizyme, an ODC inhibiting protein induced by polyamines, is involved in the process of polyamine stimulated ODC decay. In this study, we investigated the direct effect of antizyme on ODC decay in hepatoma tissue culture (HTC) cells. A truncated rat antizyme cDNA, Z1, was inserted into an expression vector at a site under the control of a glucocorticoid-inducible promoter and transfected into HTC cells. In the transfected cells dexamethasone increased the amount of Z1 mRNA and induced active antizyme in the absence of exogenous polyamines. When dexamethasone was added to cells with a high level of ODC, rapid decays of ODC activity and protein were elicited after a lag time. Cycloheximide abolished the effect of dexamethasone. These effects of dexamethasone were not observed in control HTC cells transfected with the chloramphenicol acetyltransferase gene. This study indicated that, once induced, antizyme stimulated ODC degradation independently of polyamines and strongly supported our previous hypothesis that the ODC decay accelerating action of polyamines is mediated by antizyme. PMID- 1618816 TI - Identification of potential active-site residues in the Escherichia coli leader peptidase. AB - Leader peptidase of Escherichia coli cleaves the leader sequence from the amino terminus of membrane and secreted proteins after these proteins insert across the membrane. Despite considerable research, the mechanism of catalysis of leader peptidase remains unknown. This peptidase cannot be classified using protease inhibitors to the serine, cysteine, aspartic acid, or metallo- classes of proteases (Zwizinski, C., Date, T., and Wickner, W. (1981) J. Biol. Chem. 256, 3593-3597). Using site-directed mutagenesis, we have attempted to place leader peptidase in one of these groups. We found that leader peptidase, lacking all of the cysteine residues, can cleave the leader peptide from procoat, the precursor to bacteriophage M13 coat protein. Replacement of each histidine residue with an alanyl residue was without effect on catalysis. Among all the serine and aspartic acid residues, serine 90 and serine 185 as well as aspartic acid 99, 153, 273, and 276 are necessary to cleave procoat in a detergent extract. However, only serine 90 and aspartic acid 153 were required for processing using a highly sensitive in vivo assay. In addition to the residues directly affecting catalysis, aspartic acid 99 plays a role in maintaining the structure of leader peptidase. Replacement of this residue with alanine results in a very unstable leader peptidase protein. This study thus defines two critical residues, serine 90 and aspartic acid 153, that may be directly involved in catalysis and provides evidence that leader peptidase belongs to a novel class of serine proteases. PMID- 1618817 TI - Induction of low density lipoprotein receptor and a transcription factor SP-1 by tumor necrosis factor in human microvascular endothelial cells. AB - We have previously reported that tumor necrosis factor-alpha (TNF-alpha) enhances expression of interleukin-6, collagenase, plasminogen activator inhibitor-1, and basic fibroblast growth factor genes in human omental microvascular endothelial (HOME) cells in culture. In this study, we found that treatment of HOME cells with TNF-alpha or interleukin-1 (IL-1) caused enhanced expression of low density lipoprotein (LDL) receptor. A few-fold increase in both LDL binding activity and the receptor mRNA levels was observed when HOME cells were treated with either TNF-alpha or IL-1. Northern blot analysis showed that cellular expression of LDL receptor gene was significantly increased 12-24 h after exposure to TNF-alpha. No significant changes in the life-span of LDL receptor mRNA were observed in untreated and TNF-alpha-treated cells. Scatchard analysis showed an increased receptor number for LDL in TNF-alpha-treated cells. Parallel to increased LDL binding activity, internalization and degradation of LDL were also increased in HOME cells treated with TNF-alpha or IL-1. TNF-alpha-induced enhancement of LDL receptor gene expression was not observed when cycloheximide was present. Cellular mRNA level of SP-1 gene was increased about 3-4-fold at 12 h after treatment with TNF-alpha. Nuclear run-on assays showed increased transcription of LDL receptor gene as well as SP-1 gene by TNF-alpha. Gel retardation assay with the SP-1 consensus fragment showed that SP-1 binding activity was increased about 4-5-fold 12-24 h after treatment with TNF-alpha. NF-kB binding activity was also dramatically increased, but there is no NF-kB motif on the promoter for LDL receptor gene. The induction of LDL receptor by TNF might be mediated through a transcription factor, SP-1. PMID- 1618818 TI - The influence of charge and the distribution of charge in the polar region of phospholipids on the activity of UDP-glucuronosyltransferase. AB - Studies of the mechanism of lipid-induced regulation of the microsomal enzyme UDP glucuronosyltransferase have been extended by examining the influence of charge within the polar region on the ability of lipids to activate delipidated pure enzyme. The effects of net negative charge, of charge separation in phosphocholine, and of the distribution of charge in the polar region of lipids were studied using the GT2p isoform isolated from pig liver. Prior experiments have shown that lipids with net negative charge inhibit the enzyme (Zakim, D., Cantor, M., and Eibl, H. (1988) J. Biol. Chem. 263, 5164-5169). The current experiments show that the extent of inhibition on a molar basis increases as the net negative charge increases from -1 to -2. The inhibitory effect of negatively charged lipids is on the functional state of the enzyme and is not due to electrostatic repulsion of negatively charged substrates of the enzyme. Although the inhibitory effect of net negative charge is removed when negative charge is balanced by a positive charge due to a quaternary nitrogen, neutrality of the polar region is not a sufficient condition for activation of the enzyme. In addition to a balance of charge between Pi and the quaternary nitrogen, the distance between the negative and positive charges and the orientation of the dipole created by them are critical for activation of GT2p. The negative and positive charges must be separated by the equivalent of three -CH2- groups for optimal activation by a lipid. Shortening this distance by one -CH2- unit leads to a lipid that is ineffective in activating the enzyme. Reversal of the orientation of the dipole in which the negative charge is on the polymethylene side of the lipid-water interface and the positive charge extends into water also produces a lipid that is not effective for activating GT2p. On the other hand, lipids with phosphoserine as the polar region, which has the "normal" P-N distance but carries a net negative charge, do not inhibit GT2p. This result again illustrates the importance of the dipole of phosphocholine for modulating the functional state of GT2p. PMID- 1618819 TI - Enantiomeric activation of glucuronidation in dog hepatic microsomes. AB - Isomer-specific mechanisms of conjugation were investigated by evaluating the hepatic glucuronidation of the enantiomers of the 5-lipoxygenase inhibitor zileuton. The glucuronidation of the individual isomers was stereoselective, as dog hepatic microsomes glucuronidated the S-isomer but failed to generate a glucuronide conjugate of the R-isomer. In combination, the nonglucuronidated R isomer caused a concentration-dependent increase in the rate of glucuronidation of its enantiomorph. Kinetic analysis of this interaction indicated that the R isomer affected rates of glucuronidation by decreasing the Km of the S-isomer for this process. This effect appeared enantioselective as the achiral analogue A 65838 had no effect on the Vmax and Km of S-isomer glucuronidation. The data were modeled using Michaelis-Menten kinetics in which the Km of S-isomer glucuronidation was reduced in a saturable manner by the concentration of the R isomer. These data indicate that the nonconjugated R-isomer competitively activates the glucuronidation of its enantiomorph. To our knowledge, these data represent the first demonstration of enantiomeric activation of an enzyme involved in hepatic drug metabolism. PMID- 1618820 TI - Active site topology of Saccharomyces cerevisiae lanosterol 14 alpha-demethylase (CYP51) and its G310D mutant (cytochrome P-450SG1). AB - Incubation of phenyldiazene (PhN = NH) with lanosterol 14 alpha-demethylase, a cytochrome P-450 enzyme (CYP51) that oxidatively removes the 14 alpha-methyl group of lanosterol, results in the appearance of a 478-nm band indicative of phenyl-iron complex formation. In situ oxidation of the phenyl-iron complex by ferricyanide yields exclusively the N-phenylprotoporphyrin IX regioisomer with the phenyl group on the nitrogen of pyrrole ring C (NC). The biphenyl-iron complex formed in the analogous reaction of the enzyme with biphenyldiazene similarly rearranges on treatment with ferricyanide to the NC regioisomer of N biphenylprotoporphyrin IX. The active site cavity must therefore be at least 10 A high directly above the iron atom and pyrrole ring C of the heme group, and lanosterol binds to the enzyme in the region above pyrrole ring C. Phenyl-iron complex formation is not detected spectroscopically with cytochrome P-450SG1, a catalytically inactive G310D mutant of lanosterol 14 alpha-demethylase in which the sixth iron coordination site is thought to be occupied by an imidazole ligand. Nevertheless, oxidation of the phenyldiazene-treated enzyme with ferricyanide provides the NA and NC regioisomers of N-phenylprotoporphyrin IX in a 40:60 ratio. The single amino acid substitution in cytochrome P-450SG1 thus causes a conformational change that retracts the amino acid residues that cover pyrrole ring A and moves an imidazole ligand into the active site. PMID- 1618821 TI - Escherichia coli dnaJ deletion mutation results in loss of stability of a positive regulator, CRP. AB - The dnaJ deletion mutant K7052(lambda dnaK) has a temperature-sensitive defect in the synthesis of beta-galactosidase. We confirmed this operon-specific and temperature-sensitive defect in cell-free extracts prepared from the mutant cells and found that the missing factor was CRP. In the mutant, the cellular concentration of CRP was too low to allow the expression of the lac operon at a nonpermissive temperature. Introduction of a CRP over-producing plasmid into the dnaJ deletion mutant suppressed the defect of beta-galactosidase synthesis. The lower content of CRP in the mutant was found to result from extreme instability of the protein. These results strongly suggested that the heat shock protein dnaJ is involved in the stabilization (or degradation) of CRP. PMID- 1618822 TI - Receptor binding and internalization of mouse interleukin-2 derivatives that are partial agonists. AB - Mouse interleukin-2 (mIL-2) mutant proteins with subunit-specific receptor binding defects have been previously described. Some of these mutant proteins are unable to trigger a maximum proliferative response of T cells. In this study, mIL 2 and mIL-2 mutant proteins were labeled with 32P, and their association and dissociation kinetics with the high affinity IL-2 receptor (IL-2R) were investigated. A mIL-2 mutant protein with a partial defect in binding to the low affinity component of IL-2R had a slower on-rate than mIL-2. On the other hand, a mIL-2 antagonist with a binding defect to the intermediate affinity component of IL-2R had a normal on-rate, whereas its off-rate at 37 degrees C was faster than mIL-2. This fast off-rate at physiological temperature interfered with mIL-2 internalization. When three mIL-2 partial agonists, each inducing a different maximal response, were examined, no difference was found between their dissociation rates or their internalization properties. The significance of these findings for the function of each receptor subunit in the IL-2R complex, as well as for the mechanism of activation of the receptor, is discussed. PMID- 1618823 TI - Partial phenotypic suppression of a peroxisome-deficient animal cell mutant treated with aminoglycoside G418. AB - Certain enzymes normally associated with peroxisomes, such as the dihydroxyacetone phosphate (DHAP) acyltransferase involved in plasmalogen biosynthesis, are present at low levels in peroxisome-deficient mutants of Chinese hamster ovary (CHO) cells. We now show that the aminoglycoside G418 increases the residual DHAP acyltransferase in mutant ZR-82 by 60-fold. This is accompanied by a dose- and time-dependent restoration of the plasmalogen content. G418 treatment of ZR-82 also increases residual peroxisomal beta-oxidation activity by 3.8-fold. G418 does not affect wild-type CHO cells (CHO-K1) or a different peroxisome-deficient mutant, ZR-78.1. The effects of G418 on ZR-82 are transient, since plasmalogens and DHAP-acyltransferase decline to basal levels 5 days after G418 withdrawal. Other aminoglycosides and lysosomotropic agents do not alter plasmalogen levels in ZR-82. The subcellular distribution of catalase (an enzyme of the peroxisomal matrix which is present in normal amounts in peroxisome-deficient mutants but is mislocalized in the cytosol) is unaffected by G418 treatment of ZR-82, demonstrating that G418 does not restore peroxisomes. Localization of catalase by immunofluorescence microscopy confirms a total absence of intact peroxisomes in ZR-82, either before or after exposure to G418. This study is the first to demonstrate that some peroxisome-deficient mutants can be induced to accumulate functional DHAP acyltransferase and other peroxisomal enzymes, usually missing in the absence of peroxisomes. G418 may have some therapeutic value in selected patients with inborn errors of peroxisome assembly, such as Zellweger syndrome. PMID- 1618825 TI - Evidence for two sites on rat liver plasma membranes which interact with high density lipoprotein. AB - There is little dispute that high density lipoprotein (HDL) binds to cells, however, the nature of the interaction is not fully understood. We now present evidence for a new binding site of higher affinity but lower capacity than the sites previously described in the literature. This new site is characterized by high affinity/low capacity for HDL binding (Kd = 0.94 microgram/ml, Bmax = 36 ng/mg), while the low affinity site (Kd = 36 micrograms/ml, Bmax approximately 700 ng/mg) appears to be consistent with the literature values for the interaction of HDL with cells and isolated membranes. Proteolysis of HDL with trypsin abolished its interaction with the high affinity site, suggesting an apolipoprotein requirement, while having no effect on binding to the lower affinity site. Kinetic rates of association/dissociation were determined in order to further characterize the high affinity site. At a concentration which favored the binding of HDL with the high affinity site (1 microgram/ml, 37 degrees C), the time course of association of HDL with rat liver plasma membranes, displayed a biphasic pattern, requiring 6-8 h to reach the level of binding predicted from the saturation studies. The second phase was highly sensitive to temperature, being considerably slower at 24 degrees C and totally abolished at 0 degrees C. A kinetic Kd, derived from the measured association and dissociation rate constants (Kd = 0.31 microgram/ml), was found to be of a similar magnitude to the Kd calculated for the high affinity site by Scatchard analysis (Kd = 0.94 microgram/ml). In summary, the high affinity site on rat liver plasma membranes displays an apoprotein requirement and kinetic parameters, consistent with a ligand-receptor interaction. PMID- 1618824 TI - Purification, gene cloning, and gene disruption of the transcription elongation factor S-II in Saccharomyces cerevisiae. AB - Saccharomyces cerevisiae S-II was purified to near homogeneity as a protein stimulating RNA polymerase II. Four of seven lysyl endopeptidase-digested fragments of S-II were located in the PPR2 sequence reported previously. Analysis of a genomic clone of S-II revealed that S-II and PPR2 are the same protein consisting of 309 amino acid residues, and frame shifts were found in the sequence of PPR2 gene reported previously. Yeast S-II and mouse S-II showed high similarity in their amino acid sequences, especially in their amino-terminal and carboxyl-terminal regions. A gene disruption experiment showed that an S-II null mutant was not lethal under usual growth conditions, indicating that S-II is not essential for the growth of yeast. PMID- 1618827 TI - Definition of the carbohydrate response element of the rat S14 gene. Evidence for a common factor required for carbohydrate regulation of hepatic genes. AB - The 5'-flanking region of the S14 gene from -4316 to +18 contains regulatory sequences responsible for activation of promoter activity in response to elevated carbohydrate metabolism in primary hepatocytes. To map these sequences, a series of constructs containing various internal deletions of the S14 5'-flanking sequence were assayed in primary hepatocytes. The region from -1601 to -1395 was found to be essential for this response. Comparison of the sequence of this S14 region to a region of the L-type pyruvate kinase gene that has been shown to mediate carbohydrate regulation (Thompson, K. S., and Towle, H. C. (1991) J. Biol. Chem. 266, 8679-8682) revealed a segment with 9 out of 10 identity. In both cases, this conserved sequence aligned with a DNase I footprint formed with hepatic nuclear extract. Oligonucleotides (approximately 30 base pairs) from either S14 or pyruvate kinase genes containing the conserved element bound to a hepatic nuclear factor(s) that gave identical complexes by mobility shift assay. Furthermore, these two oligonucleotides cross-competed for binding to the nuclear factor(s), suggesting that a common factor(s) binds to this conserved element. Reinsertion of the S14 oligonucleotide into an unresponsive S14 promoter construct restored the carbohydrate control. Moreover, this oligonucleotide could confer a glucose response when fused to a heterologous promoter. Thus, the S14 segment from -1457 to -1428 is a carbohydrate response element essential for the binding of nuclear factor(s) regulated by increased carbohydrate metabolism. This factor(s) may be common to the carbohydrate regulation of the S14 and pyruvate kinase genes. PMID- 1618826 TI - Purification and characterization of fatty acid ethyl ester synthase-II from human myocardium. AB - Fatty acid ethyl ester synthases metabolize ethanol nonoxidatively in those extrahepatic organs most commonly damaged by alcohol abuse. This study was designed to isolate and purify human myocardial synthase-II, one of the enzymes responsible for catalyzing the formation of fatty acid ethyl esters. DEAE cellulose chromatography of human myocardial cytosol at pH 8.0 separated synthase I, synthase-II, and synthase-III activities, eluting at conductivities of 5, 7, and 11 mS, respectively. From this elution profile, fatty acid ethyl ester synthase-II accounts for up to 50% of total synthesis in the human heart. This enzyme species was purified over 2200-fold to homogeneity after chromatography over hydroxylapatite, CM-cellulose, and hydroxylapatite. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of this homogeneous species showed a single band at 65 kDa which corresponded to its molecular weight determined by gel filtration. This molecular weight and its lack of glutathione transferase activity indicate that this species is not related to synthase-I and -III. Homogeneous synthase-II has a Vmax for palmitate, stearate, oleate, and linoleate of 70, 80, 140, and 120 nmol/mg/h, respectively. The Km for palmitate, stearate, oleate, and linoleate is 0.19, 0.12, 0.10, and 0.18 mM, respectively. The substrate specificity with respect to alcohol chain length was also investigated in the presence of 0.65 mM [14C]oleic acid. The Vmax for methanol, ethanol, propanol, and butanol was 180, 100, 280, and 410 nmol/mg/h, respectively. The Km for methanol, ethanol, propanol, and butanol was 1.16, 1.04, 0.58, and 0.33 M, respectively. The N-terminal 17-amino acid sequence of human synthase-II does not correspond to any known N-terminal amino acid sequence, indicating that this may be a novel protein. However, it has over 70% homology to a sequence close to the C terminus of rabbit cytochrome P-450IIC1 and over 50% homology to a sequence of human hemopexin starting at residue 16. Synthase-II does not cross-react with human hemopexin antibody and rat cytochrome P-450C antibody. Thus, this study provides evidence that synthase-II is a novel protein, distinct from synthase-I and -III, and it also provides a foundation for subsequent cloning and genetic studies of fatty acid ethyl ester synthase-II in man. PMID- 1618828 TI - Characterization of the interaction between the A2 subunit and A1/A3-C1-C2 dimer in human factor VIIIa. AB - Factor VIIIa is a heterotrimer of the factor VIII heavy chain-derived A1 and A2 subunits plus the factor VIII light chain-derived A3-C1-C2 subunit. While the A1 and A3-C1-C2 subunits can be isolated as a stable dimer, the A2 subunit is weakly associated with the dimer. In the human protein, the association of A2 with dimer is reversible and governed by a pH-dependent dissociation constant. Using the specific activity of factor VIIIa as an indicator of trimer concentration, the Kd (pH 6.0) was determined to be 28 nM whereas at the more physiologic pH (pH 7.4) this value was approximately 260 nM. Results from pH shift experiments confirmed the reversible binding of A2 to dimer as did the capacity for high levels of exogenous A2 subunit to inhibit the spontaneous decay of factor VIIIa activity. A2 subunit associated with the A1 subunit in the A1/A3-C1-C2 dimer based upon the capacity for free A1 subunit to inhibit the reconstitution of factor VIIIa from A2 subunit and dimer. These results indicate that the primary mechanism for the spontaneous decay of human factor VIIIa is the reversible dissociation of A2 subunit from the A1 subunit of the A1/A3-C1-C2 dimer. PMID- 1618829 TI - Hexose metabolism in pancreatic islets. Ca(2+)-dependent activation of the glycerol phosphate shuttle by nutrient secretagogues. AB - A method is proposed for the measurement of the flux through the glycerol phosphate shuttle in pancreatic islets. Such a flux is taken as the ratio between the production of 3HOH and the specific radioactivity of L-[2-3H]glycerophosphate in islets exposed to [2-3H]glycerol. D-Glucose and non-glucidic nutrient secretagogues, such as 2-ketoisocaproate and 2-aminobicyclo[2,2,1]heptane-2 carboxylate, stimulate, in a Ca(2+)-dependent manner, circulation in the glycerol phosphate shuttle. The shuttle flux is commensurate with the fraction of pyruvate generation which is not coupled with L-lactate production. These findings support the view that a rise in D-glucose concentration leads to activation of the FAD linked mitochondrial glycerophosphate dehydrogenase through an increase in cytosolic Ca2+ concentration. PMID- 1618830 TI - Resonance Raman spectra of horseradish peroxidase and bovine liver catalase compound I species. Evidence for predominant 2A2u pi-cation radical ground state configurations. AB - The nature of the porphyrin pi-cation radicals in the horseradish peroxidase and bovine liver catalase (BLC) compound I species have been investigated by studying their resonance Raman spectra. A variety of laser excitation and sample interrogation procedures have been employed in order to minimize previously documented problems arising from photoinduced conversions. With Soret band excitation, the spectra obtained for both species resemble that of a compound II like photoproduct unless the samples are excited with residence times in the microsecond regime with very low (approximately 1 milliwatt) powers. When these precautions are taken, spectra attributable to the compound I species themselves are obtained. The spectrum for horseradish peroxidase compound I is similar to that reported by Paeng and Kincaid (Paeng, K.-J., and Kincaid, J. R. (1988) Am. Chem. Soc. 110, 7913-7915) using a similar approach. Both horseradish peroxidase and BLC compound I exhibit frequency shifts relative to their compound II species that are in the direction observed for model pi-cation radicals with predominant 2A2u character. The magnitudes of these shifts are smaller than those observed for heme models that lack aromatic axial ligands, but agree well with those observed on formation of the compound I analog of N alpha-acetyl microperoxidase 8 that has His as a proximal ligand. This observation is consistent with partial delocalization of the radical density onto the proximal His-170 and Tyr-357 ligands in horseradish peroxidase and BLC, respectively. The strong ligand field provided by these ligands on the proximal side and oxo ligand on the distal side of the heme group is apparently sufficient to reverse the 2A1u radical ground state preference observed for heme-like porphyrin species (e.g. octaethylporphyrins) with weak axial fields. Enhancement of several bands assigned to the Tyr-357 ligand has also been observed for BLC compound I with 406.7-nm excitation. This is attributed either to resonance with a tyrosinate--- Fe(IV) charge transfer band or to the coupling provided by radical spin delocalization onto the tyrosinate ligand. PMID- 1618831 TI - Identification of 5,6-dimethylbenzimidazole as the Co alpha ligand of the cobamide synthesized by Salmonella typhimurium. Nutritional characterization of mutants defective in biosynthesis of the imidazole ring. AB - The Co beta-cyano derivative of the cobamide isolated from Salmonella typhimurium was identified as Co alpha-(alpha-5,6-dimethylbenzimidazolyl)-Co beta cyanocobamide, indicating that this bacterium synthesizes 5,6 dimethylbenzimidazole (DMB) de novo. We found that mutants deficient in the synthesis of DMB can incorporate benzimidazole without modification to form Co alpha-(alpha-benzimidazolyl)cobamide, a cobamide that is physiologically active. The analysis of the nutritional requirements of mutants deficient in DMB synthesis identified 4,5-dimethylphenylenediamine as a putative intermediate in the synthesis of the imidazole ring of DMB. Our results suggest that the CobII region of the cob operon of S. typhimurium only encodes functions involved in the synthesis of the imidazole ring of DMB. PMID- 1618832 TI - Transport of fatty acids into human and rat peroxisomes. Differential transport of palmitic and lignoceric acids and its implication to X-adrenoleukodystrophy. AB - The different topology of palmitoyl-CoA ligase (on the cytoplasmic surface) and of lignoceroyl-CoA ligase (on the luminal surface) in peroxisomal membranes suggests that these fatty acids may be transported in different form through the peroxisomal membrane (Lazo, O., Contreras, M., and Singh, I. (1990) Biochemistry 29, 3981-3986), and this differential transport may account for deficient oxidation of lignoceric acid in X-adrenoleukodystrophy (X-ALD) (Singh, I., Moser, A. B., Goldfisher, S., and Moser, H. W. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 4203-4207). To define the transport mechanism for these fatty acids through the peroxisomal membrane and its possible implication to lignoceric acid metabolism in X-ALD, we examined cofactors and energy requirements for the transport of palmitic and lignoceric acids in isolated peroxisomes from rat liver and peroxisomes isolated from X-ALD and control fibroblasts. The similar rates of transport of palmitoyl-CoA (87.6 +/- 6.3 nmol/h/mg protein) and palmitic acid in the fatty acid activating conditions (83.4 +/- 5.1 nmol/h/mg protein) and lack of transport of palmitic acid (4% of palmitoyl-CoA transport) when ATP and/or CoASH were removed or substituted by alpha,beta-methyleneadenosine-5'-triphosphate (AMPCPOP) and/or desulfoCoA-agarose from assay medium clearly demonstrate that transport of palmitic acid requires prior synthesis of palmitoyl-CoA by palmitoyl CoA ligase on the cytoplasmic surface of peroxisomes. The 10-fold higher rate of transport of lignoceric acid (5.3 +/- 0.6 nmol/h/mg protein) as compared with lignoceroyl-CoA (0.41 +/- 0.11 nmol/h/mg protein) and lack of inhibition of transport of lignoceric acid when ATP and/or CoASH were removed or substituted with AMPCPOP or desulfoCoA-agarose suggest that lignoceric acid is transported through the peroxisomal membrane as such. Moreover, the lack of effect of removal of ATP or substitution with AMPOPCP (a nonhydrolyzable substrate) demonstrates that the translocation of palmitoyl-CoA and lignoceric acid across peroxisomal membrane does not require energy. The transport, activation, and oxidation of palmitic acid are normal in peroxisomes from X-ALD. The deficient lignoceroyl-CoA ligase (13% of control) and oxidation of lignoceric acid (10% of control) as compared with normal transport of lignoceric acid into peroxisomes from X-ALD clearly demonstrates that pathogenomonic accumulation of very long chain fatty acids (greater than C22) in X-ALD is due to the deficiency of peroxisomal lignoceroyl-CoA ligase activity. PMID- 1618833 TI - Redox ribonucleosides. Isolation and characterization of 5-hydroxyuridine, 8 hydroxyguanosine, and 8-hydroxyadenosine from Torula yeast RNA. AB - Three hydroxyribonucleosides catalyzing the oxido-reduction of NADH and K3F3(CN)6 were purified from Torula yeast RNA by a series of steps including sodium dodecyl sulfate/phenol extraction, nuclease P1 digestion, alkaline phosphatase digestion, anion-exchange chromatography, and high performance liquid chromatography on an ODS column. Analysis by fast atom bombardment-mass spectrometry and 1H and 13C NMR spectroscopy led to identification of the redox ribonucleosides as 5 hydroxyuridine, 8-hydroxyguanosine, and 8-hydroxyadenosine. Their mass spectra, chromatographic behavior, UV spectra, NMR spectra, and IR spectra were identical to those from natural and synthetic sources. Oxidoreduction activities were specific for K3Fe(CN)6 as the oxidant and NADH as the reductant; and their magnitudes decreased in the order 5-hydroxycytidine, 5-hydroxyuridine, 8 hydroxyguanosine, and 8-hydroxyadenosine. The fact that these nucleosides have redox activities suggests new functional roles for RNAs as catalysts. PMID- 1618834 TI - Polyethylene glycol enhanced refolding of bovine carbonic anhydrase B. Reaction stoichiometry and refolding model. AB - Polyethylene glycol (PEG) inhibited aggregation during refolding of bovine carbonic anhydrase B (CAB) through the formation of a nonassociating PEG intermediate complex. Stoichiometric concentrations of PEG were required for complete recovery of active protein during refolding at aggregating conditions. For example, a PEG (Mr = 3350) to CAB molar ratio ([PEG]/[CAB]) of 2 was sufficient to inhibit aggregation during refolding at 1.0 mg/ml (33.3 microM) protein and 0.5 M guanidine hydrochloride. In addition, the PEG concentration required for enhancement was dependent upon the molecular weight and only molecular weights between 1000 and 8000 were effective in inhibiting aggregation. In the presence of PEG, the rate of refolding was the same as that observed for refolding without the formation of associated species. Refolding in the presence of PEG resulted in the rapid formation of a PEG complex with the molten globule first intermediate, and this PEG-intermediate complex did not aggregate. The CAB refolding kinetics in the presence of PEG were determined and used to develop a model of the PEG enhanced refolding pathway. The mathematical model was validated by independent activity measurements of CAB refolding. This model predicted that PEG enhanced refolding of CAB occurred by a specific interaction of PEG with the molten globule first intermediate to form a nonassociating complex which continued to fold at the same rate as the first intermediate. The predicted pathway and binding properties of PEG indicate that PEG enhanced refolding may be analogous to chaperonin mediated protein folding. PMID- 1618835 TI - Kinetics of colchicine binding to purified beta-tubulin isotypes from bovine brain. AB - Tubulin, the constituent protein of microtubules, is an alpha beta heterodimer; both alpha and beta exist in several isotypic forms whose functional significance is not precisely known. The antimitotic alkaloid colchicine binds to mammalian brain tubulin in a biphasic manner under pseudo-first-order conditions in the presence of a large excess of colchicine (Garland, D. L. (1978) Biochemistry 17, 4266-4272). We have studied the kinetics of colchicine binding to purified beta tubulin isotypes and find that each of the purified beta-tubulin isotypes binds colchicine in a monophasic manner. The apparent on-rate constants for the binding of colchicine to alpha beta II-, alpha beta III-, and alpha beta IV-tubulin dimers are respectively 132 +/- 5, 30 +/- 2, and 236 +/- 7 M-1 s-1. When the isotypes are mixed, the kinetics become biphasic. Scatchard analysis revealed that the isotypes differ significantly in their affinity constants (Ka) for binding colchicine. The affinity constants are 0.24 x 10(6), 0.12 x 10(6), and 3.31 x 10(6) M-1, respectively, for alpha beta II-, alpha beta III-, and alpha beta IV-tubulin dimers. Our results are in agreement with the hypothesis that the beta-subunit of tubulin plays a major role in the interaction of colchicine with tubulin. Our binding data raise the possibility that the tubulin isotypes might play important regulatory roles by interacting differently with other non-tubulin proteins in vivo, which in turn, may regulate microtubule-based functions in living cells. PMID- 1618836 TI - Comparison of terbium (III) luminescence enhancement in mutants of EF hand calcium binding proteins. AB - The luminescent isomorphous Ca2+ analogue, Tb3+, can be bound in the 12-amino acid metal binding sites of proteins of the EF hand family, and its luminescence can be enhanced by energy transfer from a nearby aromatic amino acid. Tb3+ can be used as a sensitive luminescent probe of the structure and function of these proteins. The effect of changing the molecular environment around Tb3+ on its luminescence was studied using native Cod III parvalbumin and site-directed mutants of both oncomodulin and calmodulin. Titrations of these proteins showed stoichiometries of fill corresponding to the number of Ca2+ binding loops present. Tryptophan in binding loop position 7 best enhanced Tb3+ luminescence in the oncomodulin mutant Y57W, as well as VU-9 (F99W) and VU-32 (T26W) calmodulin. Excitation spectra of Y57F, F102W, Y65W oncomodulin, and Cod III parvalbumin revealed that the principal Tb3+ luminescence donor residues were phenylalanine or tyrosine located in position 7 of a loop, despite the presence of other nearby donors, including tryptophan. Spectra also revealed conformational differences between the Ca2+- and Tb(3+)-bound forms. An alternate binding loop, based on Tb3+ binding to model peptides, was inserted into the CD loop of oncomodulin by cassette mutagenesis. The order of fill of Tb3+ in this protein reversed, with the mutated loop binding Tb3+ first. This indicates a much higher affinity for the consensus-based mutant loop. The mutant loop inserted into oncomodulin had 32 times more Tb3+ luminescence than the identical synthetic peptide, despite having the same donor tryptophan and metal binding ligands. In this paper, a ranking of sensitivity of luminescence of bound Tb3+ is made among this subset of calcium binding proteins. This ranking is interpreted in light of the structural differences affecting Tb3+ luminescence enhancement intensity. The mechanism of energy transfer from an aromatic amino acid to Tb3+ is consistent with a short range process involving the donor triplet state as described by Dexter (Dexter, D. L. (1953) J. Chem. Phys. 21, 836). This cautions against the use of the Forster equation in approximating distances in these systems. PMID- 1618837 TI - Follicle-stimulating hormone inhibits granulosa cell 5 alpha-reductase activity. Possible role of 5 alpha-reductase as a steroidogenic pubertal switch. AB - In order to elucidate the role of 5 alpha-reductase in the ovarian pubertal transition from 5 alpha-reduced to non-5 alpha-reduced steroids, we examined the characteristics and regulation of granulosa cell (GC) 5 alpha-reductase activity. Maximum activity was observed at 37 degrees C and at a pH of 6.5-8.0. Synthetic 4 aza-3-oxosteroids proved to be potent inhibitors (76% inhibition at 0.1 microM) of ovarian 5 alpha-reductase activity, and 20 alpha-DHP was a better substrate than either progesterone or testosterone (4- or 7-fold higher affinity constants, respectively). The Km (20 alpha-DHP) of the enzyme was 0.50 +/- 0.03 microM and 0.75 +/- 0.20 microM in homogenates of whole ovaries and GC, respectively. 17 beta-Estradiol was a non-competitive inhibitor (KI = 6.97 microM). 5 alpha Reductase activity was 22-fold (immature) to 68-fold (mature) higher in liver than ovary and 4-fold higher in theca-interstitial shells than in isolated GC. Ovarian 5 alpha-reductase activity decreased markedly with age (greater than 60% inhibition in mature, randomly cycling rats as compared to immature rats). In vivo administration of follicle-stimulating hormone (FSH) to immature rats produced a dose-dependent decrease in GC 5 alpha-reductase activity (36 +/- 1.1% and 46 +/- 5.9% inhibition following 12 micrograms and 24 micrograms FSH, respectively). Similarly, the in vitro provision of FSH (100 ng/ml) to cultured GC from immature rats resulted in (36-59%) inhibition in 5 alpha-reduced steroids. Inasmuch as FSH promotes GC development and the advancement of puberty, its ability to "switch-off" ovarian 5 alpha-reductase activity may enhance the formation of biologically potent (i.e. non-5 alpha-reduced) progestins as well as the availability of aromatizable androgens, in the best interests of pubertal steroidogenesis. PMID- 1618838 TI - Increased expression of protein kinase C alpha plays a key role in retinoic acid induced melanoma differentiation. AB - Differentiation of B16 mouse melanoma cells induced by retinoic acid (RA) is preceded by a large increase in protein kinase C alpha (PKC alpha) mRNA and protein. To determine the role of PKC alpha in the differentiation program, we stably transfected B16-F1 cells with a plasmid containing the full length PKC alpha cDNA driven by an SV40 promoter. Two out of thirty-two colonies screened were determined to overexpress PKC by 2-4-fold according to Western blot analysis and PKC enzyme activity. When compared to control cells (wild-type cells and cells transfected only with the neomycin resistance gene), PKC alpha overexpressing clones displayed longer doubling times, diminished anchorage independent growth, and increased melanin production. RA treatment of control cells mimicked these phenotypic characteristics. When injected subcutaneously into syngeneic mice, PKC alpha overexpressing clones produced smaller tumors and had longer latencies than control cells. These findings, combined with the fact that phorbol esters down-regulate PKC and antagonize RA action suggest that PKC alpha plays a key role in the RA-induced melanoma differentiation. PMID- 1618839 TI - Association of the type II cAMP-dependent protein kinase with a human thyroid RII anchoring protein. Cloning and characterization of the RII-binding domain. AB - The type II cAMP-dependent protein kinase (PKA) is localized to specific subcellular environments through binding of the dimeric regulatory subunit (RII) to anchoring proteins. Subcellular localization is likely to influence which substrates are most accessible to the catalytic subunit upon activation. We have previously shown that the RII-binding domains of four anchoring proteins contain sequences which exhibit a high probability of amphipathic helix formation (Carr, D. W., Stofko-Hahn, R. E., Fraser, I. D. C., Bishop, S. M., Acott, T. E., Brennan, R. G., and Scott J. D. (1991) J. Biol. Chem. 266, 14188-14192). In the present study we describe the cloning of a cDNA which encodes a 1015-amino acid segment of Ht 31. A synthetic peptide (Asp-Leu-Ile-Glu-Glu-Ala-Ala-Ser-Arg-Ile Val-Asp-Ala-Val-Ile-Glu-Gln-Val -Lys-Ala-Ala-Tyr) representing residues 493-515 encompasses the minimum region of Ht 31 required for RII binding and blocks anchoring protein interaction with RII as detected by band-shift analysis. Structural analysis by circular dichroism suggests that this peptide can adopt an alpha-helical conformation. Both Ht 31 (493-515) peptide and its parent protein bind RII alpha or the type II PKA holoenzyme with high affinity. Equilibrium dialysis was used to calculate dissociation constants of 4.0 and 3.8 nM for Ht 31 peptide interaction with RII alpha and the type II PKA, respectively. A survey of nine different bovine tissues was conducted to identify RII binding proteins. Several bands were detected in each tissues using a 32P-RII overlay method. Addition of 0.4 microM Ht 31 (493-515) peptide to the reaction mixture blocked all RII binding. These data suggest that all anchoring proteins bind RII alpha at the same site as the Ht 31 peptide. The nanomolar affinity constant and the different patterns of RII-anchoring proteins in each tissue suggest that the type II alpha PKA holoenzyme may be specifically targeted to different locations in each type of cell. PMID- 1618840 TI - Purification and characterization of a novel proline-directed protein kinase from bovine brain. AB - A novel protein kinase which phosphorylates a synthetic peptide substrate (RRPDAHRTPNRAF) has been purified approximately 200,000-fold from bovine brain. This peptide contains the consensus sequence for phosphorylation by the p34cdc2 kinase. The purification procedure took advantage of the phenomenon that this novel brain kinase, in partially purified extracts, chromatographed on a gel filtration column as a high molecular weight complex which dissociated in buffer containing 1 M NaCl. The purified native enzyme was estimated to be approximately 63,000, and displayed two bands of M(r) = 33,000 and 25,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. On Western immunoblot, the M(r) = 33,000 peptide reacted strongly with antibodies specific for a conserved amino terminal sequence, weakly with antibodies to the conserved PSTAIRE sequence, and not at all with antibodies to the carboxyl terminus, of HeLa cell p34cdc2. The brain kinase and p34cdc2 were similar in displaying good activity toward the parent peptide substrate, but no activity toward peptide analogues in which the T-P- motif was substituted with either -T-G- or -T-A-. Both kinases showed marked preference in phosphorylating a peptide derived from H1 histone (KTPKKAKKPKTPKKAKKL), and both kinases could be phosphorylated by the src-family tyrosine kinase, p56lyn, purified from bovine spleen. However, the brain kinase did not co-purify with a subunit having a molecular weight corresponding to known cyclins, nor did it undergo specific interaction with p13suc1 beads, suggesting that this enzyme is distinct from p34cdc2. PMID- 1618841 TI - Influence of membrane fluidity on the assembly of Staphylococcus aureus alpha toxin, a channel-forming protein, in liposome membrane. AB - By use of multilamellar phosphatidylcholine (PC) liposomes of different acyl composition and cholesterol content as model membranes, we studied whether or not membrane fluidity affects the assembly process of Staphylococcus aureus alpha toxin. Under conditions using fluid and solid membranes, we assayed accessibility (or hemolytic activity) of liposome-bound alpha-toxin to rabbit erythrocytes added, hexamerization of membrane-bound toxin using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) under nondenaturating conditions, and susceptibility of liposome-bound toxin to trypsin digestion. Our data indicated 1) that alpha-toxin bound to PC membrane as a hemolytically active monomer (or reversibly bound state); 2) that when the membrane was fluidized either by phase transition of PC or by inclusion of cholesterol over 20 mol %, the hemolytically active monomer of the toxin was irreversibly converted to nonhemolytic monomer (and/or unstable oligomer) in a first-order kinetics with a t1/2 of about 1 min, and thereafter hexamerization of the toxin gradually proceeded in the following 60-90 min; 3) that alpha-toxin might have different topology and/or conformation in PC membrane, depending on the presence or absence of cholesterol in the PC membrane; and 4) that coexistence of unsaturated acyl chain-carrying PC and cholesterol was a prerequisite for efficient hexamerization of alpha-toxin in membrane. Thus, increase in membrane fluidity promoted the assembly process of S. aureus alpha-toxin. PMID- 1618842 TI - Hm1 muscarinic cholinergic receptor internalization requires a domain in the third cytoplasmic loop. AB - Selected regions of the Hm1 muscarinic cholinergic receptor were mutated to analyze the molecular mechanisms of agonist-induced receptor internalization (or sequestration). The wild-type and mutant Hm1 genes were expressed, using pSG5, in U293 human kidney cells. Whereas surface receptor density measured with the polar tracer N-[3H]methylscopolamine was rapidly reduced by carbachol exposure, total receptor content measured with [3H]quinuclidinyl benzilate did not decline for at least 24 h, indicating the absence of extensive receptor down-regulation in U293 cells. Carbachol stimulation of phosphatidylinositol turnover paralleled receptor internalization, both with EC50 values of 10-20 microM. Furthermore, a D71N point mutation that prevented receptor activation also abolished carbachol-induced receptor internalization, indicating that receptor activation (but not necessarily second messenger stimulation) was required for internalization. Truncation of the COOH-terminal tail (K447 trunc) and point mutations of several potential Ser and Thr phosphorylation sites to Ala failed to affect receptor activation and internalization. In contrast, partial deletions of the third intracellular loop (i3) (Tyr208-Thr366) resulted in receptor mutants deficient in agonist-induced receptor internalization/sequestration. Various deletions caused either complete loss of internalization (d 232-358) or impaired internalization, ranging from 10 to 30% over 2 h, whereas wild-type Hm1 internalized to approximately 50%. Whereas the reason for the observed differences among the deficient deletion mutants remains unclear, the initial rate of N [3H]methylscopolamine binding loss from the cell surface was much slower than that of wild-type Hm1 in each case. The deletion of only one single domain, 284 292 (SMESLTSSE), in the middle of i3 was consistently associated with impaired internalization. Domain 284-292 is partially conserved among closely related muscarinic receptors, whereas most of the remainder of i3 is not (except for the i3 membrane junctions), and similar Ser- and Thr-rich regions are present in many other G protein-coupled receptors. We propose that a small receptor domain in the middle of the i3 loop of Hm1 is involved in agonist-induced receptor internalization. PMID- 1618843 TI - Hemoglobin-binding site on human haptoglobin. Identification of lysyl residues participating in the binding. AB - The locus of human haptoglobin (Hp) molecules that interacts with human hemoglobin (Hb) was examined by the differential labeling technique. First, amino groups of Hp were extensively labeled with ethyl acetimidate (EAI) either in the free state (experiment A) or in the equimolar complex with Hb (experiment B). Each of the labeled Hp samples was reduced and S-carboxymethylated, and the remaining amino groups were then allowed to react with trinitrobenzenesulfonic acid (TNBS) under denatured conditions. Only 0.6 mol/mol of the trinitrophenyl (TNP) group was introduced into the heavy chain of Hp in experiment A, whereas 2.5 mol/mol of TNP groups were into the same chain in experiment B. The extent of TNP modification for the light chain was very low in either of the experiments. The amino acid residues carrying TNP groups in the heavy chain were identified by the peptide mapping procedure. They were Ile1, Lys136, and Lys218 in experiment B, and only Ile1 in experiment A. These findings suggest that epsilon-amino groups of Lys136 and Lys218 in the heavy chain are both situated within the Hb binding locus of Hp, and that the alpha-amino group of Ile1 is buried inside the molecule either in the presence or absence of Hb. PMID- 1618844 TI - Substrate specificity of phospholipase B from guinea pig intestine. A glycerol ester lipase with broad specificity. AB - The substrate specificity of a calcium-independent, 97-kDa phospholipase B purified from guinea pig intestine was further investigated using various natural and synthetic lipids. The enzyme was equally active toward enantiomeric phosphatidylcholines under conditions allowing a strict phospholipase A activity. The lysophospholipase activity declined with the following substrates: 1-acyl-sn glycero-3-phosphocholine greater than 1-palmitoyl-propanediol-3-phosphocholine greater than 1-palmitoyl-glycol-2-phosphocholine, suggesting some influence of the polar residue vicinal to the cleavage site. The enzyme also acted on various neutral lipids including triacylglycerol, diacylglycerol, and monoacylglycerol, whereas cholesteryl oleate remained refractory to enzymatic hydrolysis. The lipase hydrolyzed sequentially the sn-2 and sn-1 acyl ester bonds of diacylglycerol, although some direct cleavage of the external acyl ester bond could also occur, as shown with diacylglycerol analogues bearing a nonhydrolyzable alkyl ether or amide bond in the sn-1 or sn-2 position. The three main activities of the enzyme (phospholipase A2, lysophospholipase, and diacylglycerol lipase) were resistant to 4-bromophenacyl bromide, but they were inhibited by N-ethylmaleimide, 5,5'-dithiobis-(2-nitrobenzoic acid), and diisopropyl fluorophosphate, suggesting the possible involvement of both cysteine and serine residues in a single active site. It is concluded that guinea pig intestinal phospholipase B, which was also detected in rat and rabbit, is actually a glycerol ester lipase with broad substrate specificity and some unique enzymatic properties. PMID- 1618845 TI - Partial characterization of the major lipooligosaccharide from a strain of Haemophilus ducreyi, the causative agent of chancroid, a genital ulcer disease. AB - The first preliminary structure of a surface lipooligosaccharide from Haemophilus ducreyi has been determined. The major oligosaccharide was released by mild acid hydrolysis and analyzed by liquid secondary ion and tandem mass spectrometry. The mass spectral data combined with composition and methylation analysis yielded the most probable structure; Gal1----4GlcNAc1----3Gal1----4Hep1----6Glc1----( Hep1--- 2Hep1----)3,4Hep1---- KDO, where the reducing terminal 3-deoxy-D-manno octulosonic acid (or KDO) exists in an anhydro form. This anhydro species results from the elimination of a phosphate from C-4 of KDO during mild acid hydrolysis. The core heptose trisaccharide consists of L-glycero-D-manno-heptose, but analysis of the peracetylated sugars indicated that the 1,4-linked heptose is likely D-glycero-D-manno-heptose. The monoclonal antibody 3F11 generated against Neisseria gonorrhoeae also binds to this lipooligosaccharide and suggests that the terminal trisaccharide is Gal beta 1----4GlcNAc beta 1----3Gal beta 1----, an epitope found in the glycose moiety of the human erythrocyte glycosphingolipid lactoneotetraglycosylceramide. Mass spectrometric and composition analysis of the lipid A moiety shows that it is similar to the lipid A of Haemophilus influenzae strain I-69 Rd-/b+ proposed by Helander et al. (Helander, I. M., Lindner, B., Brade, H., Altmann, K., Lindberg, A. A., Rietschel, E. T., and Zahringer, U. (1988) Eur. J. Biochem. 177, 483-492). Electrospray mass spectrometric analysis of the intact O-deacylated lipooligosaccharides gave an average Mr of 2710, and supported an overall structure consisting of the above nonasaccharide linked directly to a diphosphorylated lipid A moiety through the single KDO which is phosphorylated. This structure should provide a framework to investigate the roles of lipooligosaccharides in the host immunochemical response and pathology of H. ducreyi infection, a leading cause of genital ulcer disease. PMID- 1618846 TI - Structural requirements for tRNA methylation. Action of Escherichia coli tRNA(guanosine-1)methyltransferase on tRNA(1Leu) structural variants. AB - The Escherichia coli enzyme tRNA(m1G)methyltransferase, one of a group of post transcription tRNA-modifying enzymes, shows remarkable specificity in selecting the tRNA species and the specific guanosine base to be methylated. To examine the structural basis of this specificity, we synthesized a total of 15 modifications of tRNA(1Leu) and measured their methylation reaction kinetics in vitro. Elimination of any one of the three tRNA side loops, the V loop, the T loop, or the D loop, reduced the Vmax for methylation by about 1 order of magnitude. Elimination of all three side loops reduced Vmax by about 2 orders of magnitude. Clearly, gross tRNA structure is important for full enzyme activity. At the bottom of the stem proximal to the anticodon loop, in the pair at positions 31 39, substitution of a G-C for a C-G, a change that should not weaken the helical structure, had little effect on Vmax or Km. However, substitution of a G for a C increased Vmax and Km, whereas substitution of a C for G sharply reduced Vmax and, to a lesser extent, Km. These results appear to be a consequence of the principle that purines are better than pyrimidines in the stacking of adjacent bases for stability. Stacking in the stem structure appears to be important for methylation enzyme activity. In the anticodon loop itself, changing a U to a C had little effect, but changing the G of the anticodon to a C reduced Vmax over 20-fold, demonstrating the importance of the presence of the anticodon G adjacent to the G being methylated for enzyme recognition. PMID- 1618848 TI - Hysteretic behavior of nitrate reductase. Evidence of an allosteric binding site for reduced pyridine nucleotides. AB - In the absence of NADH, at 25 degrees C, partially purified NADH:nitrate reductase undergoes an approximately 50% reduction of its initial activity during 2 h. With the increase of inactivation, the NADH and nitrite concentration time curves become typical "sigmoidal," i.e. the reaction velocity of the nitrate reductase catalyzed reaction goes through a maximum before equilibrium is reached. About 80% of the original activity of nitrate reductase is restored when the enzyme is incubated for 2 min with 200 microM NADH or NADPH. Also other NADH substrate analogues have similar effects in restoring the lost activity. After incubation with the reduced pyridine nucleotides, the sigmoidal appearance of the NADH concentration time curve disappears almost completely. Despite the fact that NADPH increases the activity of the enzyme, NADPH does not show any competition with the NADH-binding site of nitrate reductase and does not produce nitrite in the absence of NADH. It is therefore concluded that there must be an additional allosteric site which binds either NADH or NADPH, or other pyridine nucleotides with the effect of increasing the activity of the enzyme. A kinetic model is presented which simulates the observed experimental findings. PMID- 1618847 TI - Brefeldin A enhances receptor-mediated transcytosis of transferrin in filter grown Madin-Darby canine kidney cells. AB - The effects of brefeldin A (BFA) on transferrin (Tf) transcellular transport, Tf receptor (TfR) distribution, and TfR-mediated endocytosis in filter-grown Madin Darby canine kidney (MDCK) cells were studied. BFA (1.6 micrograms/ml) markedly enhanced the transcytosis of 125I-labeled Tf (125I-Tf) in both apical-to-basal and basal-to-apical directions; yet, BFA did not enhance the transcytosis of either native horseradish peroxidase (HRP) or membrane-bound HRP-poly(L-lysine) conjugates. Furthermore, this enhanced transcytosis of 125I-Tf was abolished either by competition with excess unlabeled Tf or by incubation at temperatures less than or equal to 25 degrees C. In addition, BFA treatment to MDCK cells: (a) increased 125I-Tf specific binding to the apical membrane and decreased 125I-Tf specific binding to the basal membrane; (b) decreased TfR recycling at the basolateral membrane; (c) altered the apical/basolateral distribution of TfRs in favor of the apical side; and (d) markedly increased 59Fe extraction, but not transcytosis, from apically endocytosed 59Fe-loaded Tf. These effects are consistent with a model in which BFA alters the traffic pattern of internalized Tf by decreasing basolateral TfR recycling, while diverting the nonrecycled fraction to the apical side of the cell. Our results indicate that, unlike the reported inhibition of polymeric IgA transcytosis (Hunziker, W., Whitney, J. A., and Mellman, I. (1991) Cell 67, 617-627), BFA can enhance the transcytosis of Tf in MDCK cells. Thus, by altering the intracellular traffic of ligand-receptor complexes, BFA can elicit either a decrease or an increase in transcytosis depending on the nature of the intracellular receptor processing. PMID- 1618849 TI - 5' flanking sequences of the murine adenosine deaminase gene direct expression of a reporter gene to specific prenatal and postnatal tissues in transgenic mice. AB - Adenosine deaminase (ADA), an enzyme of purine metabolism, is highly expressed in four tissues of the mouse: the maternal decidua, the fetal placenta, the keratinizing epithelium of the upper alimentary tract (tongue, esophagus, and forestomach), and the absorptive epithelium of the proximal small intestine. ADA is produced at relatively low levels in all other tissues. To identify genetic elements that direct appropriate prenatal and postnatal expression of the ADA gene, a segment of DNA including the ADA promoter and 6.4 kilobases of the adjacent 5' flanking region was tested for the ability to direct the expression of a reporter gene in transgenic mice. In seven lines of transgenic mice studied, this construct directed high levels of reporter gene expression in the placenta and forestomach and exhibited correct developmental regulation in these tissues. This construct failed to direct significant reporter gene expression to either the maternal decidua or the proximal small intestine. Thus, different gene regulatory elements are required to target high expression to the four tissues characterized by high levels of ADA. PMID- 1618850 TI - Differential role of insulin receptor autophosphorylation sites 1162 and 1163 in the long-term insulin stimulation of glucose transport, glycogenesis, and protein synthesis. AB - The long-term regulatory effect of insulin on glucose transport activity and glucose transporter expression was examined in Chinese hamster ovary (CHO) transfectants that overexpress either human insulin receptors of the wild type (CHO-R cells) or human insulin receptors mutated at two major autophosphorylation sites, Tyr1162 and Tyr1163 (CHO-Y2 cells). Previous studies showed that, when acutely stimulated by insulin, CHO-Y2 cells exhibit decreased receptor kinase activity along with decreased signaling of several pathways, including that for glucose transport, as compared with CHO-R cells. We now report the following. (i) When treated for 24 h with insulin (10(-10) to 10(-6) M), CHO-R and CHO-Y2 cells displayed closely similar concentration-dependent increases in 2-deoxyglucose uptake. In both transfectants, the maximal insulin-induced increase (approximately 3.5-fold) in uptake was cycloheximide-sensitive and was paralleled by equivalent increases in the levels of GLUT-1 immunoreactive protein and mRNA. (ii) By contrast, under similar conditions, CHO-Y2 cells exhibited a marked decrease in their response to insulin for [U-14C]glucose incorporation into glycogen (decreased sensitivity and maximal responsiveness) and for [U 14C]leucine incorporation into protein (decreased sensitivity) as compared with CHO-R cells. (iii) After a 24-h treatment with 10(-7) M insulin, CHO-R (but not CHO-Y2) cells showed a decreased ability to respond to a subsequent acute insulin stimulation of either receptor exogenous kinase activity or 2-deoxyglucose uptake as compared with respective untreated controls. These results indicate that (i) insulin receptors mutated at Tyr1162 and Tyr1163 retain normal signaling of the long-term stimulatory effect of insulin on glucose transport activity and GLUT-1 expression, but not on glycogenesis and overall protein synthesis; (ii) these three insulin signaling pathways may be triggered by distinct domains of the insulin receptor beta-subunit; and (iii) wild-type (but not twin-tyrosine mutant) receptors undergo negative regulation by chronic insulin treatment for subsequent signaling of acute biological actions of insulin. PMID- 1618852 TI - Purification of nuclear proteins that bind to cisplatin-damaged DNA. Identity with high mobility group proteins 1 and 2. AB - The biochemical processes responsible for the recognition and repair of cisplatin damaged DNA in human cells are not well understood. We have developed a damaged DNA affinity precipitation technique that allows the direct visualization and characterization of cellular proteins that bind to cisplatin-damaged DNA. The method separates damaged DNA-binding proteins from complex radiolabeled cell mixtures and further resolves them into individual polypeptides by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This technique is complementary to gel retardation and Southwestern blotting analyses that have been previously used to identify cellular components that specifically bind to cisplatin-damaged DNA. Using this technique, we have characterized a set of HeLaS3 nuclear proteins of 26.5, 28, 90, and 97 kDa that specifically bind to cisplatin-DNA adducts. Competition studies with soluble cisplatin-damaged DNA confirmed these findings. The major cisplatin-damaged DNA-binding proteins of 26.5 and 28 kDa recognized adducts of DNA modified with cisplatin but not with its trans-isomer or with UV radiation. These proteins were purified 450-fold to near homogeneity by ion exchange and cisplatin-damaged DNA affinity chromatography. Amino-terminal sequence analysis showed that the 26.5- and 28-kDa proteins were identical to high mobility group (HMG) proteins HMG-2 and HMG-1, respectively. PMID- 1618851 TI - CAP-50, a newly identified annexin, localizes in nuclei of cultured fibroblast 3Y1 cells. AB - A 50-kDa protein, which binds to the growth-regulated gene (2A9) product, calcyclin in a calcium-dependent manner, was purified from bovine lung. Partial amino acid sequencing of the protein revealed it to be the bovine equivalent of rabbit lung CAP-50 (calcyclin-associated protein, 50 kDa), which is a member of the annexin family and binds to calcyclin in a calcium-dependent manner. Specific polyclonal antibodies to bovine lung CAP-50 were prepared. Comparative studies between CAP-50 and synexin (annexin VII) on the immunoreactivity against anti-CAP 50 antibodies and the ability of binding to calcyclin revealed that CAP-50 was a distinct molecule from synexin. Using specific polyclonal antibodies to bovine lung CAP-50, tissue distribution and subcellular distribution of CAP-50 were investigated. In most rat tissues, except those in the central nervous systems and kidney, CAP-50 is expressed at a high or moderate level. Both studies by subcellular fractionation and by indirect immunofluorescence staining of the rat embryonic fibroblast cell line, 3Y1, revealed that CAP-50 mainly localized in nuclei. Moreover, between the cells at interphase and at mitotic phase, different distributions of CAP-50 were observed. That is, in the cells at interphase, CAP 50 seemed to localize throughout the nucleoplasm. On the other hand, in the cells during mitosis, CAP-50 was concentrated at the loop-like structure around the mitotic apparatus. CAP-50 was found in isolated 3Y1 nuclei lacking outer nuclear membranes, and approximately 50% of CAP-50 was extracted from the nuclei by chelating calcium. Thus, CAP-50, a unique annexin, localizes in nuclei. PMID- 1618853 TI - Identification and localization of multiple forms of serine hydroxymethyltransferase in pea (Pisum sativum) and characterization of a cDNA encoding a mitochondrial isoform. AB - Serine hydroxymethyltransferase (SHMT) has been purified from the mitochondria of green pea leaves. Activity can be fractionated into two distinct peaks by ion exchange chromatography. While these two forms of the enzyme are immunologically indistinguishable, immunoinhibition experiments show the presence of a distinct non-mitochondrial third form of the enzyme to also be present in green pea leaves. While this mitochondrial form of SHMT is abundant in leaves it is absent from roots, although the two tissues have comparable SHMT activity. An antibody raised to purified mitochondrial SHMT was used to screen a cDNA expression library. The sequence of one of the isolated positive clones contained an open reading frame, which encoded a sequence that matched the amino acid sequence determined from the N terminus of the mature protein. The open reading frame encodes a mature protein of 487 amino acids with a M(r) of 54,000, together with a 27-31 amino acid serine-rich leader sequence, presumably required for mitochondrial targeting. The cDNA hybridizes to a small multigene family of 2-3 genes, which appear to be expressed predominantly in leaves. Comparison of the deduced amino acid sequence with the amino acid sequences of the rabbit mitochondrial and cytoplasmic SHMT, show that pea mitochondrial SHMT is equally similar to both of these enzymes. In addition, the rabbit sequences are more like one another than they are to the pea sequence, suggesting an interesting evolutionary relationship for these proteins. PMID- 1618854 TI - Regulation of rat glutathione S-transferase Ya subunit gene expression. DNA protein interaction at the antioxidant responsive element. AB - We have characterized the interaction of the antioxidant responsive element (ARE) in the 5'-flanking region of the rat glutathione S-transferase Ya subunit gene with its trans-acting factor. The ARE core sequence, 5'-ggTGACaaaGC-3', previously identified as the cis-acting element required for activation of the Ya subunit gene by planar aromatic compounds and phenolic antioxidants, is shown to be the high affinity recognition motif for a trans-acting factor(s) as determined by gel mobility shift assays as well as methylation interference and protection studies. The DNA-protein interaction appears to occur in the major groove and involves the GpG dinucleotide preceding and the G residue within the TGAC tetramer on the coding strand of the core sequence. In addition, DNase I protection analysis maps an extended region 5' from the core recognition motif, which was shown previously to be essential for basal activity of the ARE. The trans-acting factor is present in nuclear extracts from untreated and tert butylhydroquinone-treated cells as determined by photochemical cross-linking experiments. The cross-linked protein appears to be a heterodimer with subunit molecular weights of approximately 28,000 and approximately 45,000. PMID- 1618855 TI - Characteristics of the F52 protein, a MARCKS homologue. AB - A recently cloned mouse cDNA designated F52 encodes a putative protein with striking sequence similarity to the MARCKS protein, a major cellular substrate for protein kinase C (PKC). Major regions of sequence similarity include the amino-terminal myristoylation consensus sequence and the central calmodulin binding/PKC phosphorylation site domain. The F52 protein was expressed in Escherichia coli with apparent M(r) 50,000; it was a substrate for PKC and comigrated on two-dimensional electrophoresis with a myristoylated protein whose phosphorylation was stimulated by phorbol 12-myristate 13-acetate in mouse neuroblastoma cells. The F52 protein also was myristoylated in E. coli by co expression with N-myristoyltransferase. A 24-amino acid peptide derived from the protein's phosphorylation site domain was a good substrate for PKC; like the cognate MARCKS peptide, it was phosphorylated with high affinity (S0.5 = 173 nM) and positive cooperativity (KH = 5.4). The F52 peptide also bound calmodulin with high affinity (Kd = less than 3 nM); this binding could be disrupted by phosphorylation of the peptide with PKC, with a half-time of 8 min. The F52 protein is clearly a member of the MARCKS family as defined by primary sequence; in addition, the two proteins share several key attributes that may be functionally important. PMID- 1618856 TI - Regulated degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in permeabilized cells. AB - We have studied the regulated degradation of the enzyme 3-hydroxy-3 methylglutaryl-coenzyme A (HMG-CoA) reductase within the endoplasmic reticulum in cells permeabilized with digitonin. Using Chinese hamster ovary cells transfected with a plasmid encoding HMGal, a chimeric protein containing the membrane domain of HMG-CoA reductase coupled to beta-galactosidase, we have demonstrated mevalonate and sterol-stimulated loss of beta-galactosidase activity. In pulse chase experiments we have demonstrated mevalonate-stimulated degradation of both HMGal and HMG-CoA reductase. The rate of mevalonate-stimulated degradation observed in permeabilized cells tends to be slightly slower than that observed in intact cells treated with mevalonate and is dependent upon incubation of cells with mevalonate prior to permeabilization. The degradation process measured in this report extends a previous report of HMG-CoA reductase degradation in digitonin-permeabilized cells (Leonard, D. A., and Chen, H. W. (1987) J. Biol. Chem. 262, 7914-7919) by mimicking key physiological features of the in vivo process, including: stimulation by regulatory molecules, specifically mevalonate and sterols; inhibition by cycloheximide; and inhibition by an inhibitor of neutral cysteine proteases. PMID- 1618858 TI - Reconstitution of the activities of the RecBCD holoenzyme of Escherichia coli from the purified subunits. AB - The Escherichia coli RecBCD holoenzyme and the individual constituent subunits have been purified from overproducing strains. The purified RecBCD holoenzyme has a native molecular mass of approximately 330 kDa, indicative of a heterotrimer subunit assembly. The RecB, RecC, and RecD subunits can associate in vitro to give nuclease, helicase, ATPase, and Chi-specific endonuclease activities which are indistinguishable from those of the RecBCD holoenzyme. At concentrations at which the reconstituted RecB + C + D enzyme is very active, none of the individual RecB, RecC, or RecD subunits have readily detectable activities of the holoenzyme, except RecB protein which had previously been shown to exhibit DNA dependent ATPase activity (Hickson, I. D., Robson, C. N., Atkinson, K. E., Hutton, L., and Emmerson, P. T. (1985) J. Biol. Chem. 260, 1224-1229). At higher concentrations and with shorter DNA substrates reconstituted RecBC protein exhibits low levels of helicase and exonuclease activity. PMID- 1618857 TI - Isolation and characterization of a novel cardiac adenylylcyclase cDNA. AB - A novel adenylylcyclase cDNA (type V) was isolated from a canine heart cDNA library. Northern blotting indicates that the expression of this message is most abundant in heart with a lesser amount in brain but is absent in a variety of other tissues including lung, kidney, skeletal muscle, lymphocyte, and testis. The putative protein product predicted from the cDNA sequence has the motif of tandem six-transmembrane spans separated by a large hydrophilic cytoplasmic loop as seen in other members of the adenylylcyclase family. When this protein is expressed using a CMT cell transient expression system, the adenylylcyclase activity was stimulated by NaF, GTP gamma S, and forskolin, but not by calmodulin. The activity was inhibited in a concentration-dependent manner with either P-site active agents such as adenosine or in the presence of calcium. These data indicate that the protein encoded by this cDNA is adenylylcyclase with the biochemical features characteristic of the cardiac isoform. PMID- 1618859 TI - Isolation and characterization of a novel trypsin-like protease found in rat bronchiolar epithelial Clara cells. A possible activator of the viral fusion glycoprotein. AB - A novel trypsin-like protease associated with rat bronchiolar epithelial Clara cells, named Tryptase Clara, was purified to homogeneity from rat lung by a series of standard chromatographic procedures. The enzyme has apparent molecular masses of 180 +/- 16 kDa on gel filtration and 30 +/- 1.5 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Its isoelectric point is pH 4.75. Studies with model peptide substrates showed that the enzyme preferentially recognizes a single arginine cleavage site, cleaving Boc-Gln-Ala-Arg-4-methylcoumaryl-7-amide most efficiently and having a pH optimum of 7.5 with this substrate. The enzyme is strongly inhibited by aprotinin, diisopropylfluorophosphate, antipain, leupeptin, and Kunitz-type soybean trypsin inhibitor, but inhibited only slightly by Bowman-Birk soybean trypsin inhibitor, benzamidine, and alpha 1-antitrypsin. Immunohistochemical studies indicated that the enzyme is located exclusively in the bronchiolar epithelial Clara cells and colocalized with surfactant. An immunoreactive protein with a molecular mass of 28.5 kDa was also detected in airway secretions by Western blotting analyses, suggesting that the 30-kDa protease in Clara cells is processed before or after its secretion. Proteolytic cleavage of the hemagglutinin of influenza virus is a prerequisite for the virus to become infectious. Tryptase Clara was shown to cleave the hemagglutinin and activate infectivity of influenza A virus in a dose dependent way. These results suggest that the enzyme is a possible activator of inactive viral fusion glycoprotein in the respiratory tract and thus responsible for pneumopathogenicity of the virus. PMID- 1618860 TI - Transcriptional repression of the C/EBP-alpha and GLUT4 genes in 3T3-L1 adipocytes by tumor necrosis factor-alpha. Regulations is coordinate and independent of protein synthesis. AB - We have previously demonstrated the ability of tumor necrosis factor-alpha (TNF) to down-regulate the expression of GLUT4 (insulin-responsive glucose transporter) and C/EBP-alpha (CCAAT/enhancer-binding protein) (Stephens J. M., and Pekala, P. H. (1991) J. Biol. Chem. 266, 21839-21845). As C/EBP-alpha has been suggested to control GLUT4 expression, we have examined the time course for attenuation of transcription of these genes. Run-on transcription assays indicate a coordinate transcriptional repression of both GLUT4 and C/EBP-alpha genes (as well as the 422/aP2 gene, the adipocyte lipid-binding protein, whose expression has also been proposed to be controlled by C/EBP-alpha). Inhibition of transcription was observed within 1 h of TNF addition, with maximal suppression observed after 4 h. The inhibition was not blocked by cycloheximide. Okadaic acid treatment (1 h, 0.5 microM) also resulted in the coordinate transcriptional repression of the C/EBP alpha, GLUT4, and 422/aP2 genes, consistent with involvement of a kinase phosphatase system in the regulation of these genes. The decrease in C/EBP-alpha protein content was detectable 4 h after TNF addition and declined to 25% of controls within 24 h. A minor decrease in the protein content of GLUT4 was observed during the first 24 h of exposure to TNF; however, after 72 h of exposure GLUT4 protein was not detectable. The rapid coordinate transcriptional regulation of C/EBP-alpha, GLUT4, and 422/aP2 by TNF in the presence of cycloheximide suggests that the TNF-induced loss of GLUT4 protein may be mediated by a post-translational modification of an existing transcription factor. However, the rapid loss of C/EBP-alpha protein may be a contributing factor to further transcriptional suppression of the GLUT4 gene at the later time points. In addition to the transcriptional effect, we report that TNF-induced destabilization of these mRNAs contributes to decreased expression of all three genes. PMID- 1618861 TI - Identification of palmitoylation sites on CD4, the human immunodeficiency virus receptor. AB - We report that the cell surface glycoprotein CD4 expressed in HeLa cells can be metabolically labeled with [3H]palmitic acid. Analysis of the 3H-label after hydrolysis of the protein indicated that it was incorporated predominantly as palmitic acid. Comparison of the amount of [3H]palmitate incorporated into CD4 with that incorporated into a protein known to contain one molecule of esterified palmitate suggested that one to two molecules of palmitate were added to CD4. The fatty acid was readily cleaved from CD4 by treatment with weak base suggesting a thioester linkage. Mutations of each of 2 cysteine residues, Cys394 and Cys397, in CD4 at the junction of the transmembrane and cytoplasmic domains reduced labeling with [3H]palmitic acid, and mutation of both cysteines eliminated labeling. These results indicate that both cysteines are esterified to palmitate. Modification with palmitate was not required for expression of CD4 on the cell surface or for binding of p56lck to its cytoplasmic domain. PMID- 1618862 TI - Bordetella pertussis adenylate cyclase toxin. Structural and functional independence of the catalytic and hemolytic activities. AB - The Bordetella pertussis calmodulin-dependent adenylate cyclase (CyaA) is a 1706 residue-long toxin, endowed with hemolytic activity. We have constructed B. pertussis mutant strains producing modified CyaAs devoid of adenylate cyclase activity. Our results show that such modified CyaAs display hemolytic activity identical to the wild-type toxin, thus demonstrating that the hemolytic activity is independent of the adenylate cyclase activity. Furthermore, B. pertussis and Escherichia coli strains producing CyaA lacking the catalytic domain (residues 1 373) were constructed. The truncated protein exhibits hemolytic activity comparable to the wild-type toxin, thus establishing that the carboxyl-terminal 1332 residues alone are endowed with hemolytic activity. Together, these findings show that adenylate cyclase and hemolytic activities are located in two distinct regions of the molecule (respectively, approximately amino acids 1-400 and 401 1706) and that the two regions of CyaA are functionally independent. PMID- 1618863 TI - Antibodies selected from whole antiserum by fusion proteins as tools for the study of the topology of mitochondrial membrane proteins. Evidence that the N terminal extremity of the sixth alpha-helix of the uncoupling protein is facing the matrix. AB - The reactivity to freeze-thawed mitochondria or submitochondrial particles of a whole antiserum raised against the uncoupling protein has been investigated. Incubation with freeze-thawed brown adipose tissue mitochondria trapped antibodies reactive toward accessible parts of the uncoupling protein. One-third to one-half of antibodies against uncoupling protein which were present in the serum remained free. These antibodies were highly reactive with the vesicles obtained by sonication of mitochondria, in which the matricial side of the inner membrane was made accessible. To define epitopes recognized by the antiserum, different fusion proteins made up of MalE protein and uncoupling protein fragments were used. Immunoaffinity chromatography, using an immobilized purified fusion protein containing amino acids 253 to 290 of uncoupling protein, selected antibodies specifically directed against this part of the protein. A more precise localization of the main epitope recognized by these antibodies is proposed. These purified antibodies reacted with the protein only in submitochondrial particles, indicating a matricial orientation of this epitope. This result, associated with other data concerning uncoupling protein or related mitochondrial carriers such as the ADP/ATP translocator and the phosphate carrier, allowed us to determine the orientation of the sixth alpha-helix of the uncoupling protein. PMID- 1618864 TI - Enhanced growth of a human keratinocyte cell line induced by antisense RNA for parathyroid hormone-related peptide. AB - We have used antisense RNA technology to inhibit endogenous parathyroid hormone related peptide (PTHRP) production in the established human keratinocyte cell line, HPK1A, in order to assess the role of PTHRP as a potential modulator of cell growth. Rat PTHRP cDNA was cloned into the replication defective retroviral vector pYN in an antisense orientation and a stable cell line (HPK1A-AS) was generated after infection by amphotropic virus and selection by the neomycin derivative, G418. Expression of the transfected antisense sequence was confirmed with an RNA sense probe for PTHRP. The effect of the retrovirally mediated gene transfer on the endogenous PTHRP transcript was examined with an RNA antisense probe which demonstrated an absence of the endogenous transcript in HPK1A-AS cells. A 1.6-kilobase transcript was, however, present in equivalent quantities in both uninfected HPK1A and pYN-infected (HPK1A-pYN) cells. Immunocytochemistry and assessment of PTHRP secretion into the medium using an NH2-terminal radioimmunoassay and a UMR 106 adenylate cyclase bioassay confirmed the absence of PTHRP in HPK1A-AS cells. Examination of the inhibition of PTHRP production on cell growth demonstrated a reduction in doubling time and an increase in [3H]thymidine incorporation. Cell cycle analysis showed an increase in the proportion of the cell population in the S phase (relative to G0/G1) in HPK1A-AS cells compared to HPK1A or HPK1A-pYN cells. These data, therefore, indicate that endogenous PTHRP acts as an effective inhibitor of cell growth in this keratinocyte model and that this action occurs, at least in part, by diminishing entry into the S phase of the cell cycle. Furthermore, the antisense RNA method is a potent one to evaluate the cellular actions of PTHRP. PMID- 1618865 TI - Factor-stimulated RNA polymerase II transcribes at physiological elongation rates on naked DNA but very poorly on chromatin templates. AB - We used an in vitro assay system based on HeLa cell core transcription components to examine transcript elongation by RNA polymerase II on either naked DNA or chromatin templates as a function of the three known elongation factors, IIS, TFIIF, and TFIIX. We demonstrate for the first time that mammalian RNA polymerase II can achieve physiological elongation rates on naked DNA templates in vitro. The addition of TFIIF alone gave this rate, although IIS was required to minimize the block to elongation at intrinsic termination sites. However, IIS and TFIIF provided only a slight increase in the very poor elongation efficiency of RNA polymerase II on chromatin templates. The addition of TFIIX to reactions containing IIS and TFIIF reduced the elongation rate on naked DNA templates but slightly increased the elongation efficiency on chromatin. The ability of elongation factors either separately or in combination to stimulate transcription on naked DNA and chromatin templates was also examined. PMID- 1618866 TI - Binding of single-stranded oligonucleotides to a non-B-form DNA structure results in loss of promoter activity of the platelet-derived growth factor A-chain gene. AB - Levels of expression of the platelet-derived growth factor (PDGF) A-chain gene differ significantly in normal and transformed cells. We have identified an S1 nuclease-sensitive site in a GC box located at -55 to -72 in the PDGF A-chain promoter region. We now demonstrate that a 24-base, G-rich complementary oligonucleotide anneals specifically to the C-rich strand of the GC box and protects the GC box from nicking by S1 nuclease whereas the C-rich complementary oligonucleotide and its double-stranded counterpart do not. In transient transfection assays, expression of the PDGF A-chain gene is sharply reduced by deletions within the GC box or if the 24-base G-rich complementary oligonucleotide is preincubated with the promoter construct prior to transfection. The data suggest that the GC box of the PDGF A-chain gene may promote a non-B-form DNA structure, which is recognized by S1 nuclease and which anneals to a short complementary G-rich oligonucleotide. The data also suggest that this non-B-form DNA is important for efficient transcription of PDGF A-chain gene. PMID- 1618867 TI - Interaction between complementary polymerization sites in the structural D and E domains of human fibrin. AB - Plasmic degradation products of human fibrin, fragments DD, D, and E, bind to fibrin. It has been inferred from this observation that the binding occurs by attraction of complementary sites located in the NH2- and COOH-terminal domains of the fibrin molecule. The interaction between fragments D1 and E1 has been investigated in this work since it represents the first step in the process of fibrin clot formation. Fragment D1, that was initially as active as fragment DD, lost most of its anticoagulant activity after purification by cation-exchange chromatography. The lability of fragment D1 function explained the previous unsuccessful attempts to form a complex between fragments D1 and E1. The loss of fragment D1 anticoagulant activity was not associated with the cleavage of the gamma 63-85 chain segment, since fragments D1A and D1 identically inhibited the fibrin monomer polymerization rate. In order to demonstrate the formation of a complex between fragments D1 and E1, three lines of experiments were advanced. First, the anticoagulant activity of fragment D1 was neutralized by fragment E1 in a dose-dependent manner, demonstrating that the association between these fragments involved polymerization sites. Second, two products, D1.E1 and D1.E1.D1, were stabilized in a reaction with bifunctional cross-linking reagents, proving the formation of D.E complexes in aqueous solution. Third, immobilized fragment D1 bound fragments E1 and E2, but not fragment E3, showing that fragments E1 and E2 attached via a polymerization site to the complementary one in fragment D1, since this association was disrupted by fibrin polymerization inhibitory peptide GPRP. These results provided direct evidence for specific binding between the structural D and E domains of fibrin mediated through complementary polymerization sites. Thus, the initial formation of fibrin clot fibers appears to be driven by specific association of these sites. PMID- 1618868 TI - Post-transcriptional regulation of the human transforming growth factor-beta 1 gene. AB - Since many lines of evidence suggest that expression of the transforming growth factor-beta 1 (TGF-beta 1) gene may be regulated post-transcriptionally, we examined the effect of the 5'-untranslated region (UTR) of this gene on TGF-beta 1 expression. For this purpose, fragments of the 840-nucleotide highly GC-rich TGF-beta 1 5'-UTR were inserted into the 5'-UTR of the structural gene for human growth hormone driven by the simian virus 40 early promoter. A portion of the 5' UTR of TGF-beta 1 mRNA spanning the sequences from +11 to +147 was shown to inhibit growth hormone expression by as much as 22-fold. This effect was cell specific; growth hormone production was inhibited in PC-3 human prostate adenocarcinoma and A-549 human lung adenocarcinoma cells, while no effect was seen in rat pheochromocytoma PC12 cells, which show efficient translation of endogenous TGF-beta 1 mRNA. Computer analysis showed that this region of the 5' UTR contained a stable secondary stem-loop structure spanning sequences +49 to +76. This stem-loop region alone is sufficient to inhibit expression of the growth hormone gene, suggesting that it plays an important role in post transcriptional regulation of TGF-beta 1 gene expression. PMID- 1618869 TI - Interaction of pertussis toxin with cells and model membranes. AB - The interaction of pertussis toxin (PT) with cells and model membranes was investigated by examining PT-induced intoxication of Chinese hamster ovary cells and by studying the binding of PT and its subunits to phospholipid vesicles. Since certain bacterial toxins require an acidic environment for efficient interaction with membranes and subsequent entry into the cell, the requirement for an acidic environment for PT action was examined. PT, unlike bacterial toxins such as diphtheria toxin, did not require an acidic environment for efficient intoxication of Chinese hamster ovary cells. Potential modes by which PT might interact with biological membranes were studied by examining the binding of PT to a model membrane system. PT was found to be capable of interacting with phospholipid vesicles, however, efficient binding of the toxin to the vesicles occurred only in the presence of both ATP and reducing agent. The A subunit portion of the toxin bound preferentially to the vesicles while little binding of the B oligomer portion of PT to the model membranes was observed. Isolated A subunit, in the absence of the B oligomer, also bound to the vesicles with optimal binding occurring in the presence of reducing agent. After cleavage of the A subunit by trypsin, probably at Arg-181, Arg-182, and/or Arg-193, large fragments which lacked the C-terminal portion of the A subunit of PT no longer associated with the lipid vesicles. These results suggest that the A subunit of PT can interact directly with a lipid matrix and, if freed from the constraints imposed by the B oligomer, may be capable of interacting with cellular membranes. PMID- 1618870 TI - Parathyroid hormone inhibits 25-hydroxyvitamin D3-24-hydroxylase mRNA expression stimulated by 1 alpha,25-dihydroxyvitamin D3 in rat kidney but not in intestine. AB - Using a cDNA probe for rat renal 24-hydroxylase, expression of its mRNA was compared in the rat kidney and intestine. Vitamin D-deficient rats received a single injection of 1 alpha,25-dihydroxyvitamin D3. Expression of 24-hydroxylase mRNA was first detected in the kidney at 3-h post-injection and increased thereafter. Similarly, 24-hydroxylase mRNA was expressed in the intestine after 1 alpha,25-dihydroxyvitamin D3 injection. However, the dose level of 1 alpha,25 dihydroxyvitamin D3 required to induce the intestinal 24-hydroxylase mRNA expression was only 1/100 the amount required to induce renal 24-hydroxylase mRNA. Induction of intestinal 24-hydroxylase mRNA expression by 1 alpha,25 dihydroxyvitamin D3 was far more rapid than that of renal 24-hydroxylase mRNA. Thyroparathyroidectomy shortened the time required to induce expression of renal, but not intestinal, 24-hydroxylase mRNA. Administration of either parathyroid hormone or cAMP to vitamin D-deficient rats greatly reduced the expression of 24 hydroxylase mRNA in the kidney but not in the intestine. When rats were fed a vitamin D-repleted diet containing 0.7% (adequate) or 0.03% (low) calcium for 2 weeks, intestinal expression of 24-hydroxylase mRNA could be induced only in the low calcium group. In contrast, renal mRNA expression was preferentially stimulated in the adequate calcium group. These results clearly demonstrate that the expression of 24-hydroxylase mRNA is down-regulated by parathyroid hormone in the kidney but not in the intestine. PMID- 1618871 TI - Specific disruption of renal function and gene transcription by cyclosporin A. AB - The effects of cyclosporin A (CsA) are cell-specific, ranging from its immunosuppressive action on cells of the immune system to a variety of nonimmunologic toxic side effects. The predominant undesirable side effects of CsA occur in the kidney. Although many toxic renal effects of CsA have been described, the molecular basis of the nephrotoxicity is unknown. Elucidation of the molecular basis for the renal action of CsA may shed light on the function of cyclophilin in nonimmune cell types. The present study demonstrates that CsA selectively reduces the gluconeogenic capacity of rat proximal tubules via a decrease in activity of phosphoenolpyruvate carboxykinase (GTP:oxaloacetate carboxy-lyase (transphosphorylating), E.C. 4.1.1.32; PEPCK). The decrease in renal PEPCK activity occurs within 3 days and reflects a corresponding reduction in renal PEPCK mRNA abundance. This, in turn, is due to a selective inhibition of renal PEPCK gene transcription. Expression of several other renal genes is unaffected by CsA, as is expression of the PEPCK gene in liver. Thus, the effects of CsA are organ-specific and do not represent a general cytotoxic effect on proximal tubule cells. These results suggest that selective inhibition of the activity of a transcription factor(s) required for expression of specific genes in renal tubules may play a role in CsA-induced nephrotoxicity. PMID- 1618872 TI - Cap structure of U3 small nucleolar RNA in animal and plant cells is different. gamma-Monomethyl phosphate cap structure in plant RNA. AB - U3 small nucleolar RNA (snoRNA) is an abundant small RNA involved in the processing of pre-ribosomal RNA of eukaryotic cells. U3 snoRNA has been previously characterized from several sources, including human, rat, mouse, frog, fruit fly, dinoflagellates, slime mold, and yeast; in all these organisms, U3 snoRNA contains trimethylguanosine cap structure. In all instances where investigated, the trimethylguanosine-capped snRNAs including U3 snoRNA, are synthesized by RNA polymerase II. However, in higher plants, the U3 snoRNA is synthesized by RNA polymerase III and contains a cap structure different from trimethylguanosine (Kiss, T., and Solymosy, F. (1990) Nucleic Acids Res. 18, 1941 1949; Marshallsay, C., Kiss, T., and Filipowicz, W. (1990) Nucleic Acids Res. 18, 3451-3458; Kiss, T., Marshallsay, C., and Filipowicz, W. (1991) Cell 65, 517 526). In this study, we present evidence that cowpea and, most likely, tomato plant U3 snoRNA contains a methyl-pppA cap structure. These data show that the same U3 snoRNA contains different cap structures in different species and suggest that the kind of cap structure that an uridylic acid-rich small nuclear RNA contains is dependent on the RNA polymerase responsible for its synthesis. In vitro synthesized plant U3 snoRNA, with pppA or pppG as its 5' end, was converted to methyl-pppA/G cap structure in vitro when incubated with extracts prepared from wheat germ or HeLa cells. These data show that the capping machinery is conserved in organisms as evolutionarily distant as plants and mammals. Nucleotides 1-45 of tomato U3 snoRNA, which are capable of forming a stem-loop structure, are sufficient to direct the methyl cap formation in vitro. PMID- 1618874 TI - British Orthopaedic Association. Cambridge, UK, September 25-27, 1991. Abstracts. PMID- 1618873 TI - Mutation spectrum of copper-induced DNA damage. PMID- 1618875 TI - South African Orthopaedic Association. Johannesburg, South Africa, September 2-6, 1991. Abstracts. PMID- 1618876 TI - Improvements in rheologic properties of blood by fluid resuscitation after burn injury in rats. AB - Severe burn injury impairs tissue perfusion both by adversely altering the rheologic properties of blood and by decreasing circulating blood volume. Although resuscitation is known to improve perfusion by increasing whole blood volume, it is possible that it may also improve blood flow. To assess these latter effects of resuscitation after burn injury, we studied several determinants of blood flow. Burned animals were resuscitated with 20 ml of lactated Ringer's solution given intraperitoneally. This fluid resuscitation significantly improved the hemoconcentration that was produced by burn injury (p less than 0.05). Burn injury caused an increase in free plasma hemoglobin (p less than 0.05). Fluid resuscitation after injury reduced free plasma hemoglobin compared with that of the burned animals (p less than 0.05), although it still remained higher than free plasma hemoglobin in unburned controls (p less than 0.05). Increased whole blood viscosity and increased osmotic fragility, which were caused by burn injury, were also corrected by fluid resuscitation. Finally, the decrease in red blood cell membrane deformability that is associated with burn injury was improved by resuscitation, although it never completely returned to normal. These results demonstrate beneficial effects of fluid resuscitation on rheologic properties of blood after burn injury. Restoration of blood flow to tissue by resuscitation after burn injury may be due to improved blood rheology as well as to intravascular volume loading. PMID- 1618877 TI - Equations for the estimation of energy expenditures in patients with burns with special reference to ventilatory status. AB - There are advantages to the use of easily assessed variables for the prediction of energy expenditures of patients with burns. The purpose of this study was to determine whether height, age, sex, weight, ventilatory status, and diagnosis could be correlated with measured energy expenditures of hospitalized patients. With the use of data from 200 patients, stepwise, multivariate regression analysis derived the following equations: EEE(v) = 1925 - 10(A) + 5(W) + 281(S) + 292(T) + 851(B) (R2 = 0.43); EEE(s) = 629 - 11(A) + 25(W) - 609(O) (R2 = 0.50); where EEE = estimated energy expenditure (kcal/day), v = ventilatory dependency, s = spontaneously breathing, A = age (yr), W = body weight (kg), S = sex (male = 1, female = 0), diagnosis of T = trauma, B = burn, O = obesity present = 1, absent = 0). The equations were tested on 100 patients. Measured energy expenditures were not significantly different from calculated EEE(s) or EEE(v) (paired t test, p greater than 0.25). Energy expenditures can be accurately estimated in a variety of patients, including those with major burns with the use of easily attained information. PMID- 1618878 TI - Transcutaneous oxygen and carbon dioxide measurements for determination of skin graft "take". AB - The feasibility of using transcutaneous partial pressure of oxygen (TCPO2) and transcutaneous partial pressure of carbon dioxide (TCPCO2) measurements as a way of determining skin graft "take" was investigated in 13 patients who received partial-thickness sheet grafts. Transcutaneous measurements were obtained from the graft and an area of normal skin starting on the day of surgery and then daily for 2 weeks. No complications or discomfort resulted from the determinations. Initially, graft TCPO2 was extremely low (less than 8 mm Hg) and never rose above a value of 30 to 40 mm Hg, whereas skin levels ranged between 60 and 80 mm Hg. Graft TCPO2 levels never approached skin levels until graft maturity was achieved. Graft TCPCO2 levels were 80 to 100 mm Hg on the first few days after grafting but decreased to levels just above those of the skin (40 to 50 mm Hg) by 5 to 6 days after grafting. Graft TCPCO2 normalized at the time of clinical graft vascularization and remained levels just above those of the skin throughout the remainder of the study. Graft TCPCO2 determinations provide a noninvasive and objective measure of skin graft vascularization, and graft TCPO2 values reflect graft maturity. PMID- 1618879 TI - Depression in children after recovery from severe burns. AB - This outcome study of children and adolescents with severe burns (ages 7 to 19 years) reports that unrecognized depression is common during their lifetimes. Thirty children who had severe burns (range, 5% to 95% body surface area) were assessed for depression at a mean of 9 years after burn injury. This article presents an analysis of depression items from the Diagnostic Interview for Children and Adolescents, which was used in face-to-face interviews to assess child psychiatric disorders with diagnostic criteria from the American Psychiatric Association's Diagnostic and Statistical Manual--Third Edition. At the time that the interviews took place, only one child had symptoms of major depression and only three children had symptoms of dysthymic disorder. However, eight children had a lifetime history of major depression; two of them had been abused by burning and two had been physically or sexually abused. Four had made suicide attempts: one suicide attempt was the cause of the burn injury and three attempts were made after burn injury. Thirteen children had had suicidal thoughts, and their parents were often unaware of this. Other types of affective disorders were prevalent. There was no statistically significant association between depression and burn size or disfigurement. Although burn-related factors were associated with some depressive episodes, other biologic and social risk factors were also very important. The authors conclude that referral for diagnostic services and psychotherapy, and for some, treatment with antidepressant medication, is often a necessary part of medical services for children with burns. PMID- 1618881 TI - Aquatic access for the disabled. AB - Innovations in rehabilitation engineering can now provide aquatic access for the disabled. In the regional burn center, the Bodi-Gard cart shower system (Hospital Therapy Products, Inc., Wood Dale, Ill.) uses three flexible hoses to provide precise hydrotherapy and debridement. Its main mixing valve controls temperature and pressure and is easily disinfected by an in-line chamber. This shower system is complemented by the foldable Bodi-Gard mobile seat shower system (Hospital Therapy Products, Inc.). This system, which is covered by a disposable liner, surrounds the patient with eight water jets that empty into any floor drain. The Bather 2001 (Silcraft Corp., Traverse City, Mich.) is a fiberglass hydrotherapy bathtub with a unique Aqua-Seal door (Silcraft Corp.) that can be raised to provide patient access. Its unique closed-loop disinfection system prevents contamination of its internal components. The Nolan Tublift (Aquatic Access, Louisville, Ky.) is a lightweight, removable lift that uses water power to gently raise and lower its seat. It can be manually swiveled to allow access from a wheelchair. Transfer benches span the tub wall to provide access to the shower and bathtub. Although they are a less expensive alternative to the Tublift, they allow water to spill outside the tub, which may create a slippery bathroom floor. The Nolan Poolift (Guardian Products, Arleta, Calif.) is a water-powered pool lift, which automatically rotates as it descends. It is capable of lifting up to 135 kg with a home water pressure of 55 psi. In contrast, the water-powered Aquatic Access Poolift is a less expensive pool lift, which rotates manually with assistance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618880 TI - Reorganization of a burn unit in response to underutilization: a critical assessment. AB - The incidence of burn injury in the United States has declined over the past few years, resulting in a dramatic decrease in the number of admissions to burn centers. This decrease has generated considerable concern, leading to a variety of proposals to modify burn units to control the cost of inpatient care. In 1986 Albany Medical Center Hospital, a 654-bed regional academic health sciences center, closed its burn unit and implemented a program to manage thermally injured patients in the intensive and progressive care areas of the medical center. A retrospective study was performed to compare patient outcomes and length of stay for the dedicated burn unit and the integrated burn program. Between the year before and the year after this change there was no significant difference in mortality rate, length of stay, or number of positive blood cultures. The relationship between burn severity and length of stay was unaltered by the burn program change. A comparison of data collected just after the change to those collected 2 years later again showed no difference, except that the annual census had dropped more than 50%. The results suggest that burn units can be converted to integrated burn programs without compromising patient care outcomes, although the lack of a cohesive burn team and the unavailability of beds designated for patients with burns ultimately resulted in a deemphasis of the burn program and consequent marked reduction in the number of patients with burns seen in the institution. PMID- 1618882 TI - A survey of postoperative elbow immobilization approaches. AB - A survey of 200 North American burn units was designed to gather data about elbow immobilization positions and methods. Respondents were asked to identify the position of elbow and forearm immobilization after grafting to the upper extremity, the rationale for this, the location of the burn for the immobilization position chosen, who was responsible for immobilizing the patient's elbow after surgery, what type of material was used, and on what day range of motion to the elbow was resumed. Results indicated that elbow immobilization positions varied from full extension to more than 20 degrees of flexion, although full extension and slight flexion were used most, as was the forearm midposition. The rationale for immobilization that was most frequently given was prevention of contractures. Occupational therapists were most likely to be involved in or responsible for elbow immobilization, and thermoplastic materials were used most often. The day that range of motion was resumed also varied but was most frequently postoperative day 5. PMID- 1618883 TI - Research priorities for burn nursing: report on physiologic issues. AB - This Delphi study was designed and conducted to identify the issues of greatest concern to care of patients with burns and to the profession of burn nursing, so that nursing research could be directed toward these ends. One hundred and one questions were prioritized by the 94 participants who completed the four sequential rounds of questionnaires. A total of 11 questions (10.9%), which addressed physiologic-based issues, were identified. PMID- 1618884 TI - Vitamin C supplementation in the patient with burns and renal failure. AB - Vitamin C supplementation is an important component of nutritional management in patients with burns. To supply appropriate vitamin C therapy, complications such as renal failure must be considered. An understanding of current vitamin regimens and potential metabolic sequelae can assist the practitioner in providing safe and therapeutic vitamin C doses. PMID- 1618885 TI - "Burn repeaters" and injury control. AB - The purposes of this study were (1) to identify the percentage of patients with burns or intergenerational family members who have had previous burn injuries that required hospitalization and (2) to assess the need for an inpatient burn prevention program for patients and families. This study revealed an increase from 8% to 19% "burn repeaters," with a yearly average of 13% in a 5-year census and a 20.1% etiologic fraction related to the marker of increased risk (previous burn injury). These results strongly substantiate the necessity for an inpatient prevention program for patients and families to promote injury control by reduction of subsequent burn injury and thus break the burn injury cycle. PMID- 1618886 TI - Reconstructive goals for children with burns: are our goals the same? AB - It is often difficult if not impossible to include a pediatric patient in the planning of burn reconstruction. To give the patient greater input into his or her reconstructive plan, we developed a survey tool to evaluate the different reconstructive goals of the patient, the parent, and the physician. Each patient, parent, and physician were requested to complete a separate goal form. Each form consisted of a simple line drawing of a child that shows both anterior and posterior views. The patient, the parent, and the physician were each asked to circle the desired reconstruction site or sites. The responses were collated and compared by sex, age, size of burn, and evaluator (patient, parent, or physician). Patients indicated fewer and different desired reconstruction sites than the physicians or the parents. Before reconstruction is planned, the patient should be consulted. The desires of the parents and the physician may differ significantly from those of the patient. PMID- 1618887 TI - Interferon and interleukin-2 induced spontaneous cell-mediated cytotoxicity: a preliminary evaluation. AB - The contribution of natural cell-mediated cytotoxicity and its modulation with biological response modifiers in antitumour immunity was evaluated in patients with precancers and cancers of the oral cavity. The results were compared to those in normal controls. Both groups of patients showed highly significant depression of the natural killer cell activity. This depression was stage related, suggesting an influence of tumour or tumour products on this activity. Depression in augmentation of this cytotoxicity was evident in both patient groups with cancers and precancers, suggesting a defect in the response of killer cells to biological response modifiers for reasons other than the tumour per se. PMID- 1618888 TI - Chemical carcinogenesis of the urinary bladder--a status report. AB - Cigarette smoking and certain types of occupational exposure to arylamines appear to be the main cause of human urinary bladder cancer. Little is known of the promotion of bladder cancer in humans, although this stage has been demonstrated in rodents. Perhaps as a consequence of initiation, multifactorial alterations of cellular genes occur. These genes include the epidermal growth factor receptor gene, erbB-2, int-2, hst, and H-ras, which exert positive control over cell growth, as well as the suppressor genes Rb-1, and the gene coding for p53. Chromosomal changes such as deletions, translocations and/or amplifications related to these genes may be of significance for prognosis of this disease. PMID- 1618889 TI - Liver tumor promotion by the cyanobacterial cyclic peptide toxin microcystin-LR. AB - Certain waterblooms of toxic cyanobacteria (blue-green algae) are a health threat because of their production of toxic peptides, termed microcystins, which cause liver damage in wild and domesticated animals. The most widely studied microcystin is microcystin-LR, a heptapeptide containing the two L-amino acids, leucine and arginine. The inhibition of protein phosphatase type 1 and type 2A activities by microcystin-LR is similar to that of the known protein phosphatase inhibitor and tumor promoter okadaic acid. We show in this report that microcystin-LR, applied below the acute toxicity level, dose-dependently increases the number and percentage area of positive foci for the placental form of glutathione S-transferase in rat liver, which was initiated with diethylnitrosamine. The result was obtained independently through two animal experiments. This observation indicates that microcystin-LR is a new liver tumor promoter mediated through inhibition of protein phosphatase type 1 and type 2A activities. This provides further evidence that the okadaic acid pathway is a general mechanism of tumor promotion in various organs, such as mouse skin, rat glandular stomach and rat liver. PMID- 1618890 TI - Effects of barbiturates with or without liver-tumor-promoting activity on survival and DNA synthesis of suckling and adult rat hepatocytes in serum-free primary culture. AB - The effects of four barbiturates with or without liver-tumor-promoting activity were examined on survival and deoxyribonucleic acid (DNA) synthesis of suckling and adult rat hepatocytes in serum-free primary culture: Of the four barbiturates, two promoters, phenobarbital and barbital, enhanced DNA synthesis of suckling rat hepatocytes at low concentrations of 0.5-2 mM or 0.5 mM, but suppressed it at high concentrations of 3 mM or 1.5-4 mM. DNA synthesis of adult rat hepatocytes was, however, only suppressed by phenobarbital within the dose range tested of 1-3 mM. On the other hand, two remaining non-promoters, barbituric acid and amobarbital, did not increase but only suppressed DNA synthesis of suckling rat hepatocytes within the dose ranges of 0.5-4 mM and 0.05 0.5 mM respectively. Phenobarbital and amobarbital were effective for supporting survival and maintaining morphological features of suckling and adult rat hepatocytes at the relatively high concentrations of 3-4 mM and 0.5-0.75 mM respectively. However, barbital and barbituric acid were ineffective for maintenance of hepatocytes. The results show that the ability to support survival of primary cultured hepatocytes is not a common property of liver-tumor-promoter barbiturates but is a common property of some barbiturates with high lipophilicity, and that the maintenance of hepatocytes by phenobarbital or amobarbital is not due to a counterbalance of stimulated proliferation and death of the cells. PMID- 1618891 TI - Time-related interference of misoprostol with experimental gastric cancer formation induced by N-methyl-N'-nitro-N-nitrosoguanidine in the rat. AB - The purpose of this study was to investigate the effect of long-term misoprostol administration, at non-antisecretory doses, on N-methyl-N'-nitro-N nitrosoguanidine(MNNG)-induced gastric carcinogenesis. The incidence of gastric carcinomas and precancerous lesions was evaluated in 50 male 250-g Sprague-Dawley rats after 52 weeks of continuous oral administration of MNNG (120 mg/l; n = 20), MNNG plus misoprostol (2 mg kg-1 day-1; n = 20) or tap water (n = 10) (experiment 1), and in 30 rats treated with MNNG for 30 weeks followed by tap water (n = 15) or by misoprostol (n = 15) for 22 weeks; a third group (n = 10) received tap water only for 52 weeks (experiment 2). After sacrifice, gastric mucosal lesions were macroscopically evaluated and their histology obtained. MNNG consumption was comparable in all groups (6.5 +/- 1.1 mg rat-1 day-1). Misoprostol consumption was 180 +/- 0.25 mg kg-1 day-1 rat-1. In experiment 1 the incidence of gastric carcinomas was 60% in the MNNG group and 25% in the group treated with MNNG plus misoprostol (P less than 0.05). Cytotoxic and hyperplastic gastric mucosal lesions were also significantly reduced by misoprostol. In experiment 2 the incidence of carcinomas was 31% and 38.6% respectively. Misoprostol significantly decreased the incidence of gastric cancer formation when given from the beginning of the experiment. By contrast, when administered after 30 weeks of MNNG treatment it did not interfere with experimental gastric cancer formation. Exogenous prostaglandins are able to prevent the early MNNG-induced gastric mucosal lesions, thus interfering with gastric carcinogenesis. PMID- 1618892 TI - Protective role of aqueous turmeric extract against mutagenicity of direct-acting carcinogens as well as benzo [alpha] pyrene-induced genotoxicity and carcinogenicity. AB - Turmeric (Curcuma longa Linn.) has been shown to inhibit chemical carcinogenesis. In this study, we compared the chemopreventive efficacy of an aqueous turmeric extract (AqTE) and its constituents, curcumin-free aqueous turmeric extract (CFAqTE) and curcumin, using the Salmonella typhimurium mutagenicity assay and the bone marrow micronucleus test in female Swiss mice. AqTE exhibited antimutagenic activity against direct-acting mutagens, 4-nitro-O-phenylenediamine and 1-methyl-3-nitro-1-nitrosoguanidine, in strains TA 98 and TA 100 respectively. Both AqTE and CFAqTE inhibited the mutagenicity of benzo [alpha]pyrene in the two strains in the presence of Aroclor-1254-induced rat liver homogenate. The inhibition in both studies was dose-dependent. Administration of AqTE, CFAqTE and curcumin at a dose of 3 mg/animal 18 h prior to i.p. benzo [alpha]pyrene injection (250 mg/kg) significantly inhibited bone marrow micronuclei formation in female Swiss mice by 43%, 76%, and 65% respectively. Furthermore, the incidence and multiplicity of forestomach tumours induced by benzo [alpha]pyrene (1 mg/animal, twice weekly, p.o. for 4 weeks) in female Swiss mice were significantly inhibited by AqTE, CFAqTE and curcumin given 2 weeks before, during and after the carcinogen treatment. These data indicate that the protection against genomic damage by turmeric extract and its components tested could be necessary for some aspects of its cancer chemoprevention. PMID- 1618893 TI - Adjuvant effects of antineoplastic prostaglandins to cisplatin in nude mice bearing human ovarian cancer cells. AB - Effects of antineoplastic prostaglandins (PG) on human ovarian cancer cell growth were examined by using HR cells derived from ascites of a patient with serous cystadenocarcinoma of the ovary. With regard to inhibition of cancer cell proliferation in vitro, the effects of delta 7-PGA1 was most marked, followed by that of delta 12-PGJ2, PGJ2 and PGD2. When antineoplastic prostaglandins were administered to nude mice bearing HR cells, tumor growth in groups treated with PGJ2 and delta 12-PGJ2 alone was significantly inhibited 63 days after tumor inoculation, compared to that in an untreated group. Consequently, a significant prolongation of median survival was obtained with delta 12-PGJ2, compared to that in untreated groups and in groups with cisplatin alone. In addition, when prostaglandins were administered together with cisplatin, adjuvant inhibitory effects on the tumor growth were obtained 35, 56 and 63 days after tumor inoculation. Subsequently a significant prolongation of median survival was observed when cisplatin was combined with PGD2 or delta 7-PGA1, compared to the results in groups treated with PGD2 alone, delta 7-PGA1 alone or cisplatin alone. Combination of PGJ2 or delta 12-PGJ2 and cisplatin resulted in a significant decrease of hematocrit and body weight 63 days after tumor inoculation, suggesting a deterioration of the median survival. These results suggest that combination of PGD2 or delta 7-PGA1 with cisplatin may be of clinical use for ovarian cancer resistant to cisplatin. PMID- 1618894 TI - High-dose folinic acid and 5-fluorouracil plus cisplatin on a weekly schedule in the treatment of advanced cancer of the head and neck. AB - A group of 60 patients with advanced head/neck cancer were treated with high-dose folinic acid (500 mg/m-2/week-1) plus 5-fluorouracil (400 mg/m-2/week-1 on day 1, and cisplatin (20 mg/m-2/week-1) 24 h after folinic acid infusion was completed. Out of 55 evaluable patients, 10 patients (18%) experienced a complete response with a mean duration of 11.4+ months, 25 patients had a partial response (45%) of 6.7+ months, 6 patients (11%) showed a stabilization of 4.8+ months, and 14 (25%) progressed. The overall response rate was 63.6% (95% confidence limits 56.5% 69.5%). Patients pretreated with radiotherapy had a 67% overall response rate, while those pretreated with chemotherapy showed a 54% overall response rate. All patients with cancer of the oropharynx had a major response, while patients with cancer of the oral cavity had the lowest response rate. The mean survival of patients who attained a complete response was 14.5+ months. Partial responders had a mean survival of 10.6+ months, while patients who progresses survived a mean of 3.6+ months. The treatment has been very well tolerated with few cases of grade 3 gastrointestinal toxicity. Grade 1-2 leukopenia was recorded in 64% of cases, grade 1-2 nausea/vomiting in 85%. In one case therapy was stopped because of persistent diarrhoea. PMID- 1618895 TI - Tumor-associated eosinophilia in interleukin-2-treated patients: evidence of toxic eosinophil degranulation on bladder cancer cells. AB - Blood eosinophilia in tumor patients treated with interleukin-2 (IL-2) is well known and is regarded as evidence of toxicity or as a side-effect [Lotze et al. (1986) Arch Surg 121:1373-1379; West et al. (1987) N Engl J Med 316:898-905]. We recently described a new local IL-2 approach to therapy for advanced bladder carcinoma that allows, for the first time, high-dose continuous administration of natural interleukin-2 (nIL-2) at the tumor site without side-effects [Huland and Huland (1989) Cancer Res 49:5469-5474]. Tumor-associated eosinophilia of up to 65% (i.e. eosinophils constituting 65% of leukocytes) was seen in four of five patients after treatment, but never before treatment or in untreated controls. Activated eosinophils were attached to bladder tumor cells. Local activation was seen only after natural IL-2 treatment and was determined by cytological criteria and by staining with monoclonal antibody (mAb) EG1 directed against all eosinophil granule proteins and mAb EG2 directed against the active secretory granule proteins of the eosinophils. Bladder cancer cells in urinary sediment also stained with these two mAbs, revealing active degranulation of eosinophils on bladder tumor cells. The number of eosinophils in blood increased, however, without signs of activation. These data constitute strong evidence that activated eosinophils in vivo are involved in the IL-2-induced antitumor response. PMID- 1618896 TI - Export of mRNA from microinjected nuclei of Xenopus laevis oocytes. AB - Export of mRNA from the nucleus to the cytoplasm was studied in mature Xenopus laevis oocytes. In vitro transcribed, capped 32P-labeled mRNA was microinjected into nuclei, and its appearance in the cytoplasm measured by counting radioactivity or by RNA extraction and gel electrophoresis. Both for a 5.0-kb transferrin receptor mRNA and a 2.0-kb 4F2 antigen heavy chain mRNA we found saturable transport with an apparent Km of 3.6 x 10(8) molecules per oocyte nucleus. Under non-saturating conditions the half-time for mRNA export from the nucleus was approximately 2 min at 20 degrees C. At higher concentrations of injected mRNA this half-time was prolonged, and the maximal transport rate was reached at approximately 1.6 x 10(8) molecules/min. mRNA transport showed properties of an energy-dependent mechanism, since it was inhibited at 4 degrees C or by ATP depletion. Co-injection of the cap dinucleotide m7GpppG blocked the export effectively, suggesting a role for the cap in this process. The export was also inhibited by the pre-injection of wheat germ agglutinin. The effect of the lectin was specific and abolished by co-injection of N-acetylglucosamine. Finally, we found significant competitive inhibition in mRNA export by the presence of tRNA. Our results suggest that mRNA transport is a facilitated process which may share common steps with tRNA transport. Preliminary gel retardation experiments show that injected mRNA associates with endogenous nuclear proteins and suggest an exchange of some of the bound components during the transport to the cytoplasm. PMID- 1618897 TI - Two Saccharomyces cerevisiae kinesin-related gene products required for mitotic spindle assembly. AB - Two Saccharomyces cerevisiae genes, CIN8 and KIP1 (a.k.a. CIN9), were identified by their requirement for normal chromosome segregation. Both genes encode polypeptides related to the heavy chain of the microtubule-based force-generating enzyme kinesin. Cin8p was found to be required for pole separation during mitotic spindle assembly at 37 degrees C, although overproduced Kip1p could substitute. At lower temperatures, the activity of at least one of these proteins was required for cell viability, indicating that they perform an essential but redundant function. Cin8p was observed to be a component of the mitotic spindle, colocalizing with the microtubules that lie between the poles. Taken together, these findings suggest that these proteins interact with spindle microtubules to produce an outwardly directed force acting upon the poles. PMID- 1618898 TI - Intracellular distribution of the U1A protein depends on active transport and nuclear binding to U1 snRNA. AB - Nuclear transport of the U1 snRNP-specific protein U1A has been examined. U1A moves to the nucleus by an active process which is independent of interaction with U1 snRNA. Nuclear localization requires an unusually large sequence element situated between amino acids 94 and 204 of the protein. U1A transport is not unidirectional. The protein shuttles between nucleus and cytoplasm. At equilibrium, the concentration of the protein in the nucleus and cytoplasm is not, however, determined solely by transport rates, but can be perturbed by introducing RNA sequences that can specifically bind U1A in either the nuclear or cytoplasmic compartment. Thus, U1A represents a novel class of protein which shuttles between cytoplasm and nucleus and whose intracellular distribution can be altered by the number of free binding sites for the protein present in the cytoplasm or the nucleus. PMID- 1618899 TI - Steady state dynamics of intermediate filament networks. AB - We have conducted experiments to examine the dynamic exchange between subunit and polymer of vimentin intermediate filaments (IF) at steady state through the use of xrhodamine-labeled vimentin in fluorescence recovery after photobleaching (FRAP) analysis. The xrhodamine-vimentin incorporated into the endogenous vimentin IF network after microinjection into fibroblasts and could be visualized with a cooled charge-coupled device (CCD) camera and digital imaging fluorescence microscopy. Bar shaped regions were bleached in the fluorescent IF network using a beam from an argon ion laser and the cells were monitored at various times after bleaching to assess recovery of fluorescence in the bleached zones. We determined that bleached vimentin fibers can recover their fluorescence over relatively short time periods. Vimentin fibers in living cells also can exhibit significant movements, but the recovery of fluorescence was not dependent upon movement of fibers. Fluorescence recovery within individual fibers did not exhibit any marked polarity and was most consistent with a steady state exchange of vimentin subunits along the lengths of IF. PMID- 1618900 TI - Nerve growth factor transcriptional control of c-fos promoter transfected in cultured spinal sensory neurons. AB - High efficiency gene transfer (greater than 90%) in chicken dorsal root ganglion neurons has been obtained by DNA calcium phosphate co-precipitation, hence providing an important tool to study control of gene expression in primary neurons. Transfection with c-fos promoter sequences linked to the chloramphenicol acetyltransferase reporter gene showed that the serum responsive element functions as a strong transcriptional enhancer. Transcription from this element is developmentally regulated, and mediates the genetic response to nerve growth factor (NGF) in developing avian sensory neurons. Furthermore, NGF exerts a negative effect on transcription from the cyclic AMP responsive element, thereby supporting the involvement of tyrosine kinase activation by NGF in primary sensory neurons. PMID- 1618901 TI - Synthesis and localization of ciliary neurotrophic factor in the sciatic nerve of the adult rat after lesion and during regeneration. AB - Ciliary neurotrophic factor (CNTF) is expressed in high quantities in Schwann cells of peripheral nerves during postnatal development of the rat. The absence of a hydrophobic leader sequence and the immunohistochemical localization of CNTF within the cytoplasm of these cells indicate that the factor might not be available to responsive neurons under physiological conditions. However, CNTF supports the survival of a variety of embryonic neurons, including spinal motoneurons in culture. Moreover we have recently demonstrated that the exogenous application of CNTF protein to the lesioned facial nerve of the newborn rat rescued these motoneurons from cell death. These results indicate that CNTF might indeed play a major role in assisting the survival of lesioned neurons in the adult peripheral nervous system. Here we demonstrate that the CNTF mRNA and protein levels and the manner in which they are regulated are compatible with such a function in lesioned peripheral neurons. In particular, immunohistochemical analysis showed significant quantities of CNTF at extracellular sites after sciatic nerve lesion. Western blots and determination of CNTF biological activity of the same nerve segments indicate that extracellular CNTF seems to be biologically active. After nerve lesion CNTF mRNA levels were reduced to less than 5% in distal regions of the sciatic nerve whereas CNTF bioactivity decreased to only one third of the original before lesion levels. A gradual reincrease in Schwann cells occurred concomitant with regeneration. PMID- 1618902 TI - A multifunctional cell surface developmental stage-specific antigen in the cockroach embryo: involvement in pathfinding by CNS pioneer axons. AB - mAb DSS-8 binds to a 164-kD developmental stage-specific cell surface antigen in the nervous system of the cockroach, Periplaneta americana. The antigen is localized to different subsets of cells at various stages of development. The spatial and temporal distributions of DSS-8 binding were determined and are consistent with this antigen playing multiple roles in the development of the nervous system. Direct identification of some of these functions was made by perturbation experiments in which pioneer axon growth occurs in embryos that are cultured in vitro in the presence of mAb DSS-8 or its Fab fragment. Under these conditions the pioneer axons of the median fiber tract grow but follow altered pathways. In a smaller percentage of the ganglia, the immunoreagents additionally produce defasciculation of a subset of DSS-8 labeled axons. Therefore, direct roles for the DSS-8 antigen in both the guidance of pioneer axons and selective fasciculation have been demonstrated. PMID- 1618904 TI - Chondrodysplasia in transgenic mice harboring a 15-amino acid deletion in the triple helical domain of pro alpha 1(II) collagen chain. AB - We have generated transgenic mice by microinjection of a 39-kb mouse pro alpha 1(II) collagen gene construct containing a deletion of exon 7 and intron 7. This mutation was expected to disturb the assembly and processing of the homotrimeric type II collagen molecule in cartilage. Expression of transgene mRNA at levels equivalent or higher than the endogenous mRNA in the offspring of two founder animals resulted in a severe chondrodysplastic phenotype with short limbs, hypoplastic thorax, abnormal craniofacial development, and other skeletal deformities. The affected pups died at birth due to respiratory distress. Light microscopy of epiphyseal growth plates of transgenic pups demonstrated a marked reduction in cartilaginous extracellular matrix and disruption of the normal organization of the growth plate. The zone of proliferating chondrocytes was greatly reduced whereas the zone of hypertrophic chondrocytes was markedly increased extending deep into the diaphysis suggestive of a defect in endochondral ossification. Electron microscopic examination revealed chondrocytes with extended RER, a very severe reduction in the amount of cartilage collagen fibrils, and abnormalities in their structure. We postulate that the deletion in the alpha 1(II) collagen acts as a dominant negative mutation disrupting the assembly and secretion of type II collagen molecules. The consequences of the mutation include interference with normal endochondral ossification. These mice constitute a valuable model to study the mechanisms underlying human chondrodysplasias and normal bone formation. PMID- 1618905 TI - Kinetochores and chromatin diminution in early embryos of Parascaris univalens. AB - In Parascaris the mitotic chromosomes of gonial germline cells are holocentric and possess a continuous kinetochore along their entire length. By contrast, in meiotic cells, the centromeric activity is restricted to the heterochromatic tips where direct insertion of spindle microtubules into chromatin without any kinetochore plate is seen. In the presomatic cells of early embryos, which undergo heterochromatin elimination, only euchromatin shows kinetic activity. After developing a technique to separate the very resistant egg shell from the embryos, we studied the cell divisions during early embryogenesis by immunochemical and EM approaches. The results reported here show that in presomatic cells microtubules bind only the euchromatin where a continuous kinetochore plate is present. We also report observations suggesting that the binding of the long kinetochores to the mitotic spindle initiates to a limited number of sites and extends along the entire length, during chromosome condensation. The existence of different centromere stages in different cell types, rends Parascaris chromosomes a very good model to study centromere organization. PMID- 1618903 TI - Different extracellular domains of the neural cell adhesion molecule (N-CAM) are involved in different functions. AB - The neural cell adhesion molecule (N-CAM) engages in diverse functional roles in neural cell interactions. Its extracellular part consists of five Ig-like domains and two fibronectin type III homologous (type III) repeats. To investigate the functional properties of the different structural domains of the molecule in cell interactions and signal transduction to the cell interior, we have synthesized, in a bacterial expression system, the individual domains and tandem sets of individual domains as protein fragments. These protein fragments were tested for their capacity to influence adhesion and spreading of neuronal cell bodies, promote neurite outgrowth, and influence cellular migration patterns from cerebellar microexplants in vitro. Ig-like domains I and II and the combined type III repeats I-II were most efficient for adhesion of neuronal cell bodies, when coated as substrates. Neurite outgrowth was best on the substrate-coated combined type III repeats I-II, followed by the combined Ig-like domains I-V and Ig-like domain I. Spreading of neuronal cell bodies was best on substrate-coated combined type III repeats I-II, followed by Ig-like domain I and the combined Ig-like domains I-V. The cellular migration pattern from cerebellar microexplant cultures plated on a mixture of laminin and poly-L-lysine was modified by Ig-like domains I, III, and IV, while Ig-like domains II and V and the combined type III repeats I-II did not show significant modifications, when added as soluble fragments. Outgrowth of astrocytic processes from the explant core was influenced only by Ig like domain I. Metabolism of inositol phosphates was strongly increased by Ig like domain I and less by the Ig-like domains II, III, IV, and V, and not influenced by the combined type III repeats I-II. Intracellular concentrations of Ca2+ and pH values were increased only by the Ig-like domains I and II. Intracellular levels of cAMP and GMP were not influenced by any protein fragment. These experiments indicate that different domains of N-CAM subserve different functional roles in cell recognition and signal transduction, and are functionally competent without nervous system-derived carbohydrate structures. PMID- 1618906 TI - Correct folding of alpha-lytic protease is required for its extracellular secretion from Escherichia coli. AB - alpha-Lytic protease is a bacterial serine protease of the trypsin family that is synthesized as a 39-kD preproenzyme (Silen, J. L., C. N. McGrath, K. R. Smith, and D. A. Agard. 1988. Gene (Amst.). 69: 237-244). The 198-amino acid mature protease is secreted into the culture medium by the native host, Lysobacter enzymogenes (Whitaker, D. R. 1970. Methods Enzymol. 19:599-613). Expression experiments in Escherichia coli revealed that the 166-amino acid pro region is transiently required either in cis (Silen, J. L., D. Frank, A. Fujishige, R. Bone, and D. A. Agard. 1989. J. Bacteriol. 171:1320-1325) or in trans (Silen, J. L., and D. A. Agard. 1989. Nature (Lond.). 341:462-464) for the proper folding and extracellular accumulation of the enzyme. The maturation process is temperature sensitive in E. coli; unprocessed precursor accumulates in the cells at temperatures above 30 degrees C (Silen, J. L., D. Frank, A. Fujishige, R. Bone, and D. A. Agard. 1989. J. Bacteriol. 171:1320-1325). Here we show that full length precursor produced at nonpermissive temperatures is tightly associated with the E. coli outer membrane. The active site mutant Ser 195----Ala (SA195), which is incapable of self-processing, also accumulates as a precursor in the outer membrane, even when expressed at permissive temperatures. When the protease domain is expressed in the absence of the pro region, the misfolded, inactive protease also cofractionates with the outer membrane. However, when the folding requirement for either wild-type or mutant protease domains is provided by expressing the pro region in trans, both are efficiently secreted into the extracellular medium. Attempts to separate folding and secretion functions by extensive deletion mutagenesis within the pro region were unsuccessful. Taken together, these results suggest that only properly folded and processed forms of alpha-lytic protease are efficiently transported to the medium. PMID- 1618907 TI - Lowering the cholesterol content of MA104 cells inhibits receptor-mediated transport of folate. AB - The folate receptor is clustered on the surface of MA104 cells in association with caveolae. This relationship is thought to be essential for the proper internalization and recycling of the receptor during the delivery of 5 methyltetrahydrofolate to the cytoplasm of folate-depleted cells. Both the clustered organization of the receptor and the integrity of caveolae are disrupted when cells are deprived of cholesterol. We now show that cholesterol depletion of MA104 cells markedly reduces the rate of 5-methyltetrahydrofolate internalization and causes a 70% decline in the number of receptors present in the internal, recycling compartment. This effect is consistent with morphologic data showing that cholesterol-depleted MA104 cells have a reduced number of caveolae as well as fewer receptors per caveolae. PMID- 1618908 TI - How Listeria exploits host cell actin to form its own cytoskeleton. I. Formation of a tail and how that tail might be involved in movement. AB - After Listeria is phagocytosed by a macrophage, it dissolves the phagosomal membrane and enters the cytoplasm. The Listeria then nucleates actin filaments from its surface. These actin filaments rearrange to form a tail with which the Listeria moves to the macrophage surface as a prelude to spreading. Since individual actin filaments appear to remain in their same positions in the tail in vitro after extraction with detergent, the component filaments must be cross bridged together. From careful examination of the distribution of actin filaments attached to the surface of Listeria and in the tail, and the fact that during and immediately after division filaments are not nucleated from the new wall formed during septation, we show how a cloud of actin filaments becomes rearranged into a tail simply by the mechanics of growth. From lineage studies we can relate the length of the tail to the age of the surface of Listeria and make predictions as to the ratio of Listeria with varying tail lengths at a particular time after the initial infection. Since we know that division occurs about every 50 min, after 4 h we would predict that if we started with one Listeria in a macrophage, 16 bacteria would be found, two with long tails, two with medium tails, four with tiny tails, and eight with no tails or a ratio of 1:1:2:4. We measured the lengths of the tails on Listeria 4 h after infection in serial sections and confirmed this prediction. By decorating the actin filaments that make up the tail of Listeria with subfragment 1 of myosin we find (a) that the filaments are indeed short (maximally 0.3 microns in length); (b) that the filament length is approximately the same at the tip and the base of the tail; and (c) that the polarity of these filaments is inappropriate for myosin to be responsible or to facilitate movement through the cytoplasm, but the polarity insures that the bacterium will be located at the tip of a pseudopod, a location that is essential for spreading to an adjacent cell. Putting all this information together we can begin to unravel the problem of how the Listeria forms the cytoskeleton and what is the biological purpose of this tail. Two functions are apparent: movement and pseudopod formation. PMID- 1618909 TI - How Listeria exploits host cell actin to form its own cytoskeleton. II. Nucleation, actin filament polarity, filament assembly, and evidence for a pointed end capper. AB - After Listeria, a bacterium, is phagocytosed by a macrophage, it dissolves the phagosomal membrane and enters the cytoplasm. The Listeria than nucleates actin filaments from its surface. These newly assembled actin filaments show unidirectional polarity with their barbed ends associated with the surface of the Listeria. Using actin concentrations below the pointed end critical concentration we find that filament elongation must be occurring by monomers adding to the barbed ends, the ends associated with the Listerial surface. If Listeria with tails are incubated in G actin under polymerizing conditions, the Listeria is translocated away from its preformed tail by the elongation of filaments attached to the Listeria. This experiment and others tell us that in vivo filament assembly must be tightly coupled to filament capping and cross-bridging so that if one process outstrips another, chaos ensues. We also show that the actin filaments in the tail are capped on their pointed ends which inhibits further elongation and/or disassembly in vitro. From these results we suggest a simple picture of how Listeria competes effectively for host cell actin. When Listeria secretes a nucleator, the host's actin subunits polymerize into a filament. Host cell machinery terminate the assembly leaving a short filament. Listeria overcomes the host control by nucleating new filaments and thus many short filaments assemble. The newest filaments push existing ones into a growing tail. Thus the competition is between nucleation of filaments caused by Listeria and the filament terminators produced by the host. PMID- 1618911 TI - Heterodimerization and transcriptional activation in vitro by NF-kappa B proteins. AB - The NF-kappa B family of transcription proteins represents multiple DNA binding, rel related polypeptides that contribute to regulation of genes involved in immune responsiveness and inflammation, as well as activation of the HIV long terminal repeat. In this study multiple NF-kappa B related polypeptides ranging from 85 to 45 kDa were examined for their capacity to interact with the PRDII regulatory element of interferon beta and were shown to possess distinct intrinsic DNA binding affinities for this NF-kappa B site and form multiple DNA binding homo- and heterodimer complexes in co-renaturation experiments. Furthermore, using DNA templates containing two copies of the PRDII domain linked to the rabbit beta globin gene, the purified polypeptides specifically stimulated NF-kappa B dependent transcription in an in vitro reconstitution assay as heterodimers but not as p50 homodimers. These experiments emphasize the role of NF-kappa B dimerization as a distinct level of transcriptional control that may permit functional diversification of a limited number of regulatory proteins. PMID- 1618910 TI - Kinesin-related proteins required for assembly of the mitotic spindle. AB - We identified two new Saccharomyces cerevisiae kinesin-related genes, KIP1 and KIP2, using polymerase chain reaction primers corresponding to highly conserved regions of the kinesin motor domain. Both KIP proteins are expressed in vivo, but deletion mutations conferred no phenotype. Moreover, kip1 kip2 double mutants and a triple mutant with kinesin-related kar3 had no synthetic phenotype. Using a genetic screen for mutations that make KIP1 essential, we identified another gene, KSL2, which proved to be another kinesin-related gene, CIN8. KIP1 and CIN8 are functionally redundant: double mutants arrested in mitosis whereas the single mutants did not. The microtubule organizing centers of arrested cells were duplicated but unseparated, indicating that KIP1 or CIN8 is required for mitotic spindle assembly. Consistent with this role, KIP1 protein was found to colocalize with the mitotic spindle. PMID- 1618912 TI - Release of iron by human retinal pigment epithelial cells. AB - Retinal pigment epithelial cells, which form one aspect of the blood-retinal barrier, take up iron in association with transferrin by a typical receptor mediated mechanism (Hunt et al., 1989. J. Cell Sci. 92:655-666). This iron is dissociated from transferrin in a low pH environment and uptake is sensitive to agents that inhibit endosomal acidification. The dissociated iron enters the cytoplasm as a low molecular weight (less than 10 kD) component and subsequently binds to ferritin. No evidence for recycling of iron in association with transferrin was found. Nevertheless, much of the iron that is taken up is recycled to the extracellular medium, primarily from the low molecular weight pool. This release of iron is not sensitive to inhibitors of energy production or of vesicular acidification but is increased up to a maximum of about 40% of the total 55Fe incorporated when cells are incubated with serum or the medium is changed. When a short loading time for 55Fe from 55Fe-transferrin is used (i.e., when the low molecular weight pool is proportionately larger), a much larger fraction of the cell-associated radiolabel is released than when longer loading times are used. The data suggest that a releasable intracellular iron pool is in equilibrium with the externalized material. The released iron may be separated into a high and a low molecular weight component. The former is similar on polyacrylamide gel electrophoresis to ferritin although it cannot be immune precipitated by anti-ferritin antibodies. The low molecular weight 55Fe which is heterogeneous in nature can be bound by external apo-transferrin and may represent a form that can be taken up by cells beyond the blood-retinal barrier. PMID- 1618913 TI - Effect of osmolality on 86Rb+ uptake and release by Leishmania donovani. AB - Promastigotes from late-log phase cultures of Leishmania donovani were washed and resuspended in Hanks' Balanced Salt Solution without glucose or phenyl red but with 20 mM (N-[2-hydroxyethyl] piperazine-N'-[2-ethanesulfonic acid]) (HEPES) (HBSS-, 305 mOsm/kg). They were then added to a solution containing 86Rb such that the final osmolality and ionic composition was as desired. Samples were taken at known times and the amount of intracellular 86Rb was measured. Similarly, experiments were performed in which 86Rb was added to the cultures about 18 hr before collection, and the amount of 86Rb released from the washed cells was measured. Under iso-osmotic conditions only about 1.3% of the intracellular 86Rb was released in 900 sec. This increased about 4-fold if the osmolality was reduced from 305-153 mOsm/kg. This is much slower than the very rapid release of alanine in response to hypo-osmotic stress, indicating that alanine release is not via a non-specific pore. Reducing the temperature from 26 degrees C to 3-4 degrees C completely inhibits 86Rb release under iso-osmotic conditions and largely inhibits it under hypo-osmotic conditions. The rate of 86Rb release was not sensitive to K+ concentration and was not altered if chloride was replaced by sulfamate. Ouabain had no effect on either 86Rb uptake or release, but carbonylcyanide P-trifluoromethoxyphenylhydrazone (FCCP) reduced the rate of 86Rb release and, after about a 300 sec exposure, completely inhibited 86Rb uptake. Amiloride partially inhibited 86Rb release, but had no effect on uptake. A decrease in pH from 7.1-5.9 had little effect on 86Rb release under iso-osmotic conditions and slightly increased the rate of release under hypo-osmotic conditions, but it decreased the rate of uptake under both iso osmotic and hypo-osmotic conditions. Cells taken from 3-day stationary phase cultures released 86Rb more slowly under iso-osmotic conditions than cells from late log phase cultures, but were more responsive to hypo-osmotic stress than were log phase cells. These data appear to rule out an [Na-K-Cl] transporter or a [K-Cl] cotransporter as the means of K+ release, but are consistent with the possibility that a K+/H+ exchanger is present. The possibility that other carrier systems may be present is also discussed. PMID- 1618914 TI - Development of acute thermotolerance in L929 cells: lack of HSP28 synthesis and phosphorylation. AB - We investigated the correlation between the development of acute thermotolerance and the phosphorylation, synthesis, and expression of the HSP28 family in murine L929 cells. Following heating at 43 degrees C for 30 min, thermotolerance developed rapidly in exponential-phase cells and reached its maximum 4-9 h after heat shock. Maximal thermal resistance was maintained for 24 h and then gradually decayed. However, heat-induced phosphorylation of HSP28 was not detected. Furthermore, HSP28 synthesis during incubation at 37 degrees C for 12 h following heat shock was not detected by [3H]-leucine labeling followed by two-dimensional polyacrylamide gel electrophoresis. In addition, Northern blots failed to demonstrate expression of the HSP28 gene. Unlike HSP28, the expression of constitutive and inducible HSP70 genes, along with the synthesis of their proteins, was observed during incubation at 37 degrees C after heat shock. These results demonstrate that HSP28 synthesis and its phosphorylation are not required to develop acute thermotolerance in L929 cells. PMID- 1618915 TI - The proto-oncogene c-myc is involved in cell differentiation as well as cell proliferation: studies on growth plate chondrocytes in situ. AB - A combination of immunocytochemistry and microdensitometry has been used to localize and quantify the expression of the proto-oncogene c-myc within chondrocytes of the proximal growth plates of rat and chick long bones. Although the c-myc protein was localized in all chondrocytes of the growth plate of both species the most intense staining was restricted to the proliferating and differentiating chondrocytes. These were identified by their ability to synthesize DNA (bromodeoxyuridine positive) and the presence of alkaline phosphatase activity, respectively. Species differences did exist with the c-myc concentration of the chick proliferating and differentiating chondrocytes being higher (128% and 240%, respectively) than the respective chondrocytes of the rat. The higher c-myc concentration in the chick proliferating chondrocytes paralleled the differences in the bromodeoxyuridine labelling index between the two species. In the rat, the concentration of c-myc protein present in the differentiating chondrocytes was 74% higher than in the respective proliferating chondrocytes, while in the chick it was 146% higher. The data not only provides further evidence for a role of the c-myc protein in cell proliferation but also suggests involvement of this protein in chondrocyte differentiation and/or hypertrophy. PMID- 1618916 TI - Imaging neutrophil activation: analysis of the translocation and utilization of NAD(P)H-associated autofluorescence during antibody-dependent target oxidation. AB - Fluorescence intensified/enhanced microscopy has been used to study the metabolic activation of living human neutrophils in time-lapse sequences. The autofluorescence associated with NAD(P)H's emission band was studied within individual quiescent and stimulated cells. Excitation of NAD(P)H-associated autofluorescence was provided by a high-intensity Hg-vapor lamp. The background subtracted autofluorescence signals were computer enhanced. In some cases the ratio image of NAD(P)H-associated autofluorescence to tetramethyl-rhodamine methyl ester (TRME) fluorescence, which was found to be uniformly distributed within neutrophils, was calculated to normalize autofluorescence intensities for cell thickness. Activation of the NADPH oxidase by phorbol myristate acetate, F-, N-formyl-methionyl-leucyl-phenylalanine (FMLP), or tumor necrosis factor (TNF) dramatically reduced autofluorescence levels. Membrane solubilization with sodium dodecyl sulfate eliminated autofluorescence. Thus, control experiments indicated that most or all of the detectable NAD(P)H-associated autofluorescence was due to NAD(P)H, consistent with previous non-microscopic studies. To understand the metabolic events surrounding the internalization and oxidative destruction of targets, we have imaged the NAD(P)H-associated autofluorescence of neutrophils and the Soret band of antibody coated target erythrocytes during cell-mediated cytotoxicity. Absorption contrast microscopy of the erythrocyte's Soret band is an especially sensitive indicator of the entry of reactive oxygen metabolites into this target's cytosol. Thus, it is possible to spectroscopically dissect and image the substrate (NADPH) and product (O2-) reactions of the NADPH oxidase in living unlabeled neutrophils. During real-time experiments at 37 degrees C, the level of NAD(P)H-associated autofluorescence surrounding phagosomes greatly increases before the disappearance of the target's Soret band. NAD(P)H-associated autofluorescence in the vicinity of phagocytosed erythrocytes is greatly diminished after target oxidation. This suggests that NAD(P)H is translocated to the vicinity of phagosomes prior to the oxidation of targets. The apparent cytosolic redistribution of NAD(P)H was confirmed by ratio imaging microscopy to control for cell thickness. We suggest that NADPH including its sources and/or carriers accumulate near phagosomes prior to target oxidation and that local NADPH molecules are consumed during target oxidation. PMID- 1618917 TI - Inhibition of cell-cell adhesion and morphogenesis of Dictyostelium by carnitine. AB - Carnitine (gamma-trimethylammonium beta-hydroxy-butyric acid) possesses the novel property of preventing cell aggregation elicited by clusterin or by fibrinogen (I.B. Fritz and K. Burdzy, J. Cell. Physiol., 140:18-28 [1989]). In investigations reported here, we show that carnitine also affects cell-cell adhesion in Dictyostelium discoideum, a cellular slime mold whose cells interact in specific and complex manners during discrete stages of development. Two types of cell adhesion systems sequentially appear on the surface of developing Dictyostelium cells, involving the surface glycoprotein gp24 which mediates EDTA sensitive binding sites, and the surface glycoprotein gp80 which mediates the EDTA-resistant binding sites. Addition of increasing concentrations of D(+) carnitine and L(-)-carnitine resulted in a progressive inhibition of both the EDTA-sensitive binding sites and the EDTA-resistant binding sites of Dictyostelium cells at different stages of development. In contrast, comparable or higher concentrations of choline, acetyl-beta-methylcholine, or deoxycarnitine had no detectable effects on cell aggregation. Concentrations of carnitine required for 50% inhibition of EDTA-resistant adhesion sites were found to be dependent upon levels of gp80 expressed by Dictyostelium, with greatest inhibition by carnitine of reassociation of cells containing the lowest levels of gp80. Removal of carnitine from cells by washing resulted in the rapid restoration of the ability of Dictyostelium to form aggregates and to resume normal development. We discuss possible mechanisms by which carnitine inhibits the aggregation of cells. PMID- 1618918 TI - K-current mediation of prolactin-induced proliferation of malignant (Nb2) lymphocytes. AB - The effects of different concentrations of various K-current blockers on prolactin-induced proliferation and membrane K-currents in malignant lymphocytes (Nb2 cells) were investigated. Membrane currents were measured with the whole cell patch-clamp technique, and lymphocyte density was quantified by both spectrophotometric and conventional methods. K-current blockers tested (quinidine, 4-aminopyridine, barium, and tetraethylammonium) exhibited similar rank order potency for K-current block and inhibition of prolactin-induced proliferation of malignant lymphocytes. Because Nb2 cells proliferate independently of a transmembrane Ca-influx, these results suggest that K-currents per se rather than K-current modulation of Ca-influx is an essential event for lymphocyte proliferation. PMID- 1618919 TI - Platelet-activating factor stimulates phospholipase C activity in human endometrium. AB - Human preimplantation embryos secrete platelet-activating factor (PAF), which stimulates prostaglandin E2 synthesis from secretory endometrium. This study investigated the action of PAF on phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)-specific phospholipase C activity in human endometrium. Slices of normal endometrium were incubated with 5 microCi/ml myo-[2-3H] inositol for 3 h at 37 degrees C in 95% O2 and 5% CO2 to label tissue phosphoinositides. Inositol phosphates were extracted using trichloroacetic acid precipitation and diethylether neutralization and production was measured using Dowex 1-X8 anion exchange column chromatography. PAF induced rapid and concentration-dependent accumulation of inositol phosphates (IP) from secretory endometrium, but had no effect on endometrium removed in the proliferative phase of the menstrual cycle. The IP3 fraction was significantly elevated from a median value of 14.0 c.p.m. mg 1 dry wt [range: 8-41 c.p.m. mg-1 dry wt] to 28.0 c.p.m. mg-1 dry wt [range: 11 87 c.p.m. mg-1 dry wt, P less than 0.002] following 1 min exposure of secretory endometrium to PAF-acether, in the presence of 10 mM LiCl. PAF-induced hydrolysis of PtdIns(4,5)P2 was inhibited by the specific PAF receptor antagonist WEB 2086, in a dose-dependent manner (P less than 0.02), indicating that in human endometrium PtdIns(4,5)P2 hydrolysis is mediated via a PAF receptor. These results indicate that PAF receptor coupling activates endometrial PtdIns(4,5)P2 specific phospholipase C only in the secretory phase of the menstrual cycle, suggesting that the PAF response may be under ovarian steroid regulation. It is proposed that the ability of the endometrium to respond to PAF appears to be a feature of the preparation of this tissue for implantation and that the second messengers generated may play a role in cellular processes involved in the maternal recognition of very early human pregnancy. PMID- 1618920 TI - Effect of hypoxia upon intracellular calcium concentration of human endothelial cells. AB - Ischemia is a situation occurring in several diseases including myocardial infarction and organ transplantation in which oxygenated blood supply is impaired. Ischemia leads to many cellular and tissue modifications, the most important one being cell death. Several explanations have been proposed to account for these modifications and cell death; among them is calcium overload. However, the influence of calcium concentration on the alteration of endothelial cell functions or viability during ischemia are still unknown. We developed here an in vitro model where human endothelial cell monolayers were submitted to hypoxia with or without reoxygenation and variation in calcium concentration was followed using a specific intracellular probe Fura 2. We observed a significant increase of [Ca2+]i during 2 h hypoxia reaching values similar to those observed during agonist stimulation of endothelial cells but far lower than values toxic for the cells. This increase was constant during the hypoxic incubation and was due mainly to an influx of extracellular calcium. Viability was also followed during hypoxia and using calcium channel blockers, we could show that there was no correlation between viability and the rise in calcium concentration. During the reoxygenation period, [Ca2+]i decreased to reach the normal value of resting cells after 45 min, suggesting that cells were still able to recover their calcium homeostasis. The use of a ketone body (beta-hydroxybutyrate) indicated that an energy deficiency was responsible for the hypoxia-induced increase in [Ca2+]i. We actually observed a 43% decrease in ATP concentration after 2 h hypoxia. This decrease was already significant after 30 min which thus precedes the changes in [Ca2+]i. These results show that during hypoxia, energy deficiency led to an increase in [Ca2+]i which is, however, too low to account for the loss of viability but which is within the range of concentrations observed during stimulation of endothelial cells. We propose that such increased intracellular calcium concentrations could play a role in the synthesis of mediators leading to the development of local inflammation. PMID- 1618921 TI - Effects of acute vs. chronic phorbol ester exposure on transepithelial permeability and epithelial morphology. AB - In previous experiments we have shown that acute (30 minutes) exposure to phorbol esters or other protein kinase C activators causes increased transepithelial permeability, specifically by the increased paracellular permeability through tight junctions. However, the role of protein kinase C activators in carcinogenesis is predicted upon a chronic exposure of an effective dose at frequent intervals for a prolonged period of time. We therefore sought to determine the effect of chronic phorbol ester exposure on transepithelial permeability by exposing cells of the polar renal epithelial cell line, LLC-PK1, to phorbol esters for time periods as long as 16 weeks. The following changes ensued: (1) after the initial drop in transepithelial resistance due to phorbol ester exposure, i.e., an increase in transepithelial permeability (in the acute phase of exposure), an adaptive response occurs as transepithelial resistances in chronically exposed cultures recover to approximately 50% of control values, (2) the cell sheets in chronically exposed cultures lose their acute responsiveness of transepithelial permeability to phorbol ester exposure, (3) cell sheet architecture changes as cells occasionally multilayer and actual polyp-like cell masses appear at high frequency, and (4) cytosolic protein kinase C activity decreases to 50% of control level with acute exposure and then is further decreased to less than 1% of control level in chronically treated cells; membrane associated PKC activity is not as sharply decreased. The possible role of transepithelial permeability in carcinogenesis and the value of chronically treated epithelial cell cultures as a model for two-stage carcinogenesis are discussed. PMID- 1618922 TI - Cell density dependent effects of TGF-beta demonstrated by a plasminogen activator-based assay for TGF-beta. AB - Transforming growth factor-beta 1 (TGF-beta 1) induces a decrease in plasminogen activator (PA) expression in confluent cultures of bovine aortic endothelial (BAE) cells. We describe an assay using the suppression of PA expression in confluent BAE cells by TGF-beta 1 which detects concentrations of the growth factor ranging from 5 to 200 pg/ml and has an ED50 of 15-20 pg/ml. The assay can be performed in 96-well plates and requires a minimum of 35 ul of solution per sample, thereby limiting the amount of reagents required and allowing many samples to be tested in a single assay. Here we demonstrate that the effect of TGF-beta 1 on PA expression in BAE cells depends on the length of time the cells are exposed to the growth factor and the density at which the cells are plated. In cells plated at a high density (3.5 x 10(5) cells/cm2), both 4 h and 24 h exposures to TGF-beta 1 suppress PA expression. However, with cells plated sparsely (3.5 x 10(4) cells/cm2), a 4 h exposure to TGF-beta 1 increases PA expression 2-fold, whereas a 24 h exposure results in an 85% inhibition of basal PA expression. The paradoxical stimulation of PA expression in cells at a sparse density upon 4 h exposure to TGF-beta 1 occurs in a dose-dependent manner with an ED50 of 15-20 pg/ml. This bifunctional response of PA production in cells exposed to TGF-beta 1 may have implications with regard to the role of TGF-beta 1 in angiogenesis. PMID- 1618923 TI - Demonstration of an insulin-insensitive storage pool of glucose transporters in rat hepatocytes and HepG2 cells. AB - The subcellular distribution of glucose transporters in rat hepatocytes and HepG2 cells was studied in the absence and in the presence of insulin. Glucose transporters were quantitated by measuring glucose-sensitive cytochalasin B binding and by protein immunoblotting using isoform-specific antibodies. Plasma membrane contamination into subcellular fractions was assessed by measuring distribution of 5'-nucleotidase and cell surface carbohydrate label. In hepatocytes, GLUT-2 occurred in a low-density microsomal (LDM) fraction at a significant concentration, and as much as 15% of cellular GLUT-2 was found intracellularly that cannot be accounted for by plasma membrane contamination. In HepG2 cells which express GLUT-1 and GLUT-2, the two isoforms showed distinct subcellular distribution patterns: GLUT-2 was highly concentrated in LDM while very little GLUT-1 was found in this fraction, indicating that a large portion of GLUT-2 occurs in intracellular organelles. Insulin treatment did not change the subcellular distribution patterns of glucose transporters in both cell types. Our results suggest that rat hepatocytes and HepG2 cells possess an intracellular storage pool for GLUT-2, but lack the insulin-responsive glucose transporter translocation mechanism. PMID- 1618924 TI - Leukemia inhibitory factor/differentiation-stimulating factor (LIF/D-factor): regulation of its production and possible roles in bone metabolism. AB - Leukemia inhibitory factor/differentiation-stimulating factor (LIF/D-factor), expression of its mRNA, and possible roles in bone metabolism were studied in murine primary and clonal osteoblast-like cells. Local bone-resorbing factors such as IL-1, TNF alpha, and LPS strongly induced expression of LIF/D-factor mRNA in both clonal MC3T3-E1 cells and primary osteoblast-like cells. Neither parathyroid hormone nor 1 alpha,25-dihydroxyvitamin D3 stimulated expression of LIF/D-factor mRNA. LIF/D-factor per se did not stimulate expression of its own mRNA. Appreciable amounts of LIF/D-factor were detected in synovial fluids from rheumatoid arthritis (RA) patients but not in those with osteoarthritis (OA). Simultaneous treatment with LIF/D-factor, IL-1, and IL-6 at the concentrations found in synovial fluids from RA patients greatly enhanced bone resorption, though these cytokines did not stimulate bone resorption when separately applied. This suggests that LIF/D-factor produced by osteoblasts is in concert with other bone-resorbing cytokines such as IL-1 and IL-6 involved in the bone resorption seen in the joints of RA patients. LIF/D-factor specifically bound to MC3T3-E1 cells with an apparent dissociation constant of 161 pM and 1,100 binding sites/cell. LIF/D-factor dose-dependently suppressed incorporation of [3H]thymidine into MC3T3-E1 cells. In addition, it potentiated the alkaline phosphatase activity induced by retinoic acid, though LIF/D-factor alone had no effect on enzyme activity. These results suggest that LIF/D-factor is involved in not only osteoclastic bone resorption but also osteoblast differentiation in conjugation with other osteotropic factors. PMID- 1618925 TI - Tissue-specific regulation of glucokinase gene expression. AB - Glucokinase contributes to the maintenance of blood glucose homeostasis by catalyzing the high Km phosphorylation of glucose in the liver and the pancreatic beta cell, the only two tissues known to express this enzyme. Molecular biological studies of the glucokinase gene and its products have advanced our understanding of how this gene is differentially regulated in the liver and beta cell. The production of an active glucokinase isoform is determined by both transcriptional and post-transcriptional events. Two different promoter regions that are widely separated in a single glucokinase gene are used to produce glucokinase mRNAs in the liver, pancreatic beta cell, and pituitary. The different transcription control regions are tissue-specific in their expression and are differentially regulated. In liver, glucokinase gene expression is regulated by insulin and cAMP, whereas in the beta cell it is regulated by glucose. The upstream glucokinase promoter region, which gives rise to the glucokinase mRNA in pituitary and pancreas, is structurally and functionally different from the downstream promoter region, which gives rise to the glucokinase mRNA in liver. The use of distinct promoter regions in a single glucokinase gene enables a different set of transcription factors to be utilized in the liver and islet, thus allowing a functionally similar gene product to be regulated in a manner consistent with the different functions of these two tissues. In addition, the splicing of the glucokinase pre-mRNA is regulated in a tissue-specific manner and can affect the activity of the gene product.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1618926 TI - Alterations in glucose transporter expression and function in diabetes: mechanisms for insulin resistance. AB - Insulin resistance is a major pathologic feature of human obesity and diabetes. Understanding the fundamental mechanisms underlying this insulin resistance has been advanced by the recent cloning of the genes encoding a family of facilitated diffusion glucose transporters which are expressed in characteristic patterns in mammalian tissues. Two of these transporters, GLUT1 and GLUT4, are present in muscle and adipose cells, tissues in which glucose transport is markedly stimulated by insulin. To understand the mechanisms underlying in vivo insulin resistance, regulation of these transporters is being investigated. Studies reveal divergent changes in the expression of GLUT1 and GLUT4 in a single cell type as well as tissue specific regulation. Importantly, alterations in glucose transport in rodent models of diabetes and in human obesity and diabetes cannot be entirely explained by changes in glucose transporter expression. This suggests that defects in glucose transporter function such as impaired translocation, fusion with the plasma membrane, or activation probably contribute importantly to in vivo insulin resistance. PMID- 1618927 TI - Identification of a core motif that is recognized by three members of the HMG class of transcriptional regulators: IRE-ABP, SRY, and TCF-1 alpha. AB - Insulin induces glyceraldehyde-3-phosphate dehydrogenase (GADPH) gene transcription in part by regulating one or more proteins that bind a cis-acting element, IRE-A. We have recently cloned a protein, IRE-ABP, that binds the IRE-A element. IRE-ABP is a member of the HMG class of transcriptional regulators and is 67% identical within its HMG box domain to the candidate gene for the testis determining factor, SRY. IRE-ABP and SRY share binding specificity for the IRE-A motif. This sequence is also highly conserved with a core motif, 5'-Py-ctttg(a/t) 3', contained in T-cell specific genes that have high affinity for TCF-1 alpha, another member of the HMG class of transcriptional regulators. Thus, diverse members of the HMG family interact with similar nucleotide sequences to regulate expression of genes that initiate and maintain the differentiated phenotype. We have found this core motif in the upstream region of many genes that are positively and negatively regulated by insulin. These observations suggest that IRE-ABP or a related family member may coordinate the expression of these genes. The HMG family of proteins has diverse functions ranging from the regulation of differentiation and mating type in yeast to the regulation of tissue- and species specific gene expression in mammals. Insulin regulates GAPDH gene transcription in a tissue-specific manner. We propose that members of the IRE-ABP family play an important role in controlling tissue specificity of the insulin response. PMID- 1618928 TI - Heterotrimeric configuration is essential to the adhesive function of laminin. AB - Mouse PFHR9 laminin, B1B2-heterodimers, and free B1-chains were separated from one another by gel filtration on Superose 6. The cell attachment promoting activity of these species was measured after immunoprecipitation with monoclonal anti-laminin antibodies coupled to Sepharose 6MB beads. These antibodies, which did not react with the laminin E8 fragment, were directed against epitopes in the NH2-terminus of the laminin B1-chain and in the central region of laminin. After incubation with purified EHS laminin, the immunosorbents revealed efficient adhesion substrates for a rat rhabdomyosarcoma cell line which attached preferentially to the laminin E8 fragment. Although both were immunoprecipitated efficiently, B1B2-heterodimers and B1-chains, unlike PFHR9 laminin, did not support the attachment of RMS cells. On a molar basis B1B2-heterodimers were 24 times less efficient than PFHR9 laminin or EHS laminin in supporting cell attachment. These data suggest that heterotrimeric configuration is essential to the adhesive function of the laminin E8 fragment. PMID- 1618929 TI - Modulation of collagen and fibronectin synthesis in fibroblasts by normal and malignant cells. AB - The influence of various normal and malignant human cells on the level of collagen synthesis by human fibroblasts was tested in coculture. As revealed by immunoperoxidase staining, in cocultures with breast adenocarcinoma cells (MCF7, SA52, T47D) fibroblasts synthesized collagen while tumor cells did not. Fibroblasts displayed increased collagen production without change in the overall protein synthesis. Several other types of cells derived from normal human tissues (keratinocytes, normal mammary cells) or from fibrosarcoma, melanoma, cervical carcinoma, choriocarcinoma, or other breast adenocarcinoma (SW613, MDA, BT20) did not affect collagen synthesis of fibroblasts. Although to a lesser extent, this stimulating effect was reproduced by using the conditioned medium (CM) of the active cells but not with CM of the other cell types. A slight stimulation was also obtained when tumoral MCF7 cells and fibroblasts shared the same medium but were physically separated, suggesting that close contact was required for optimal stimulation of collagen synthesis. The collagen synthesis stimulating activity was not related to a modification of fibroblast proliferation rate. The production of collagen types I, III, and VI and fibronectin were increased in cocultures of fibroblasts with MCF7 cells. The increased synthesis of collagen types I and III and fibronectin was paralleled by similar changes in the steady state level of their mRNAs. On the contrary, the increased production of collagen type VI appeared regulated at a post-transcriptional level. PMID- 1618930 TI - Butanol-extractable and detergent-solubilized cell surface components from murine large cell lymphoma cells associated with adhesion to organ microvessel endothelial cells. AB - Metastatic variant cell lines of the murine RAW117 large cell lymphoma were used to study the cell surface components involved in syngeneic tumor cell/microvessel endothelial cell interactions. Poorly liver-metastatic parental RAW117-P cell line adhered to murine hepatic sinusoidal endothelial cell monolayers at significantly lower rates than the liver-selected, highly liver-metastatic RAW117 H10 line and both cell lines were poorly adherent to lung microvessel and bovine aorta endothelial cells. Viable, 2% 1-butanol-treated RAW117-H10 tumor cells formed fewer liver tumor nodules in experimental metastasis assays than untreated H10 cells and were significantly less adherent to murine hepatic sinusoidal endothelial cell monolayers. When 2% 1-butanol extracts of metabolically labeled or CHAPS detergent lysates of cell surface-labeled tumor cells were analyzed for their ability to bind to fixed microvessel endothelial cell monolayers, quantitative differences were found in the extractable tumor cell surface components that bound to the different organ-derived microvessel endothelial cells. Cell surface components (1-butanol extractable), of Mr approximately 85,000-90,000 and approximately 37,000-40,000 bound to hepatic sinusoidal endothelial cell monolayers to a greater extent than to murine lung microvessel endothelial or bovine aortic endothelial cell monolayers, whereas tumor cell surface components of Mr approximately 45,000, approximately 33,000, and approximately 25,000 bound similarly to endothelial cells regardless of origin. The results suggest but do not prove that tumor cell/endothelial cell adhesion involves multiple tumor cell surface components, some of which commonly bind to various endothelial cells and others for which binding may be dictated by the tissue origin and type of endothelial cell. Particular RAW117 butanol-extractable cell membrane components were associated with tumor cell-endothelial cell adhesion, and these components could be responsible, in part, for the preferential adhesion of RAW117 cells to liver sinusoidal endothelial cells and metastasis to liver. PMID- 1618931 TI - Rate transition and regulatory coupling in endocytosis of interferon-alpha and tumor necrosis factor-alpha in human epithelial tumor cells. AB - The time-dependent concentrations of interferon-alpha and tumor necrosis factor alpha associated with the membrane and internalized by cells contain information on the kinetics of endocytosis and their cellular processing. This information can be reduced quantitatively by application of the respective compartmental models. In our studies of human epithelial tumor cells interacting with human interferon-alpha and human tumor necrosis factor-alpha, we accounted only for actual endocytosis and elimination of the tracer from cells by a novel method sensitive to changes in the rate of endocytosis, to the delay in tracer elimination, and to the nonlinear regulatory coupling between endocytosis and the internalized ligand. Data reduced by this method resulted in best-fit parameter values statistically superior to values obtained by previous methods (Bajzer et al., 1989). The results indicate a change with time in the rate of endocytosis of tumor necrosis factor-alpha and the inhibition of endocytosis by the endocytosed ligand-receptor complex. We conclude that sorting and processing of interferon alpha and tumor necrosis factor-alpha are restricted by the type of both the receptor and the cell. PMID- 1618932 TI - Potential language and attentional networks revealed through factor analysis of rCBF data measured with SPECT. AB - We used changes in regional cerebral blood flow (rCBF) to disclose regions involved in central auditory and language processing in the normal brain. rCBF was quantified with a fast-rotating, single-photon emission computerized tomograph (SPECT) and inhalation of 133Xe. rCBF data were obtained simultaneously from parallel, transverse slices of the brain. The lower slice was positioned to include both Broca's and Wernicke's areas. The upper slice included regions generally regarded by neurobehaviorists as less related to primary auditory or linguistic functions. We presented three types of auditory stimuli to ten healthy, young volunteers: (a) diotically presented Danish speech, (b) dichotic word stimulation, and (c) white noise. Wilcoxon's signed ranks sum test revealed increased rCBF in language-related areas of cortex, viz., Wernicke's area and its right-sided homologous area as well as in Broca's area (left hemisphere), when subjects listened to narrative speech, compared to white noise (baseline). No significant rCBF differences were detected with this test during dichotic stimulation vs. white noise. A more sophisticated statistical method (factor analysis) disclosed patterns of functionally intercorrelated regions. The factor analysis reduced the highly intercorrelated rCBF measures from 28 regions of interest to a set of three independent factors. These factors accounted for 77% of the total variation in rCBF values. These three factors appeared to represent statistical analogues of independent brain networks involved in (I) auditory/linguistic, (II) attentional, and (III) visual imaging activity. PMID- 1618933 TI - Decreases in frontal and parietal lobe regional cerebral blood flow related to habituation. AB - We previously reported decreased mean CBF between consecutive resting conditions, ascribed to habituation. Here we address the regional specificity of habituation over three consecutive flow studies. Regional CBF (rCBF) was measured in 55 adults (12 right-handed men, 12 right-handed women, 14 left-handed men, 17 left handed women), with the 133Xe inhalation technique, during three conditions: resting, verbal tasks (analogies), and spatial tasks (line orientation). Changes in rCBF attributable to the cognitive tasks were eliminated by correcting these values to a resting equivalent. There was a progressive decrease in mean rCBF over time, reflecting habituation. This effect differed by region, with specificity at frontal (prefrontal, inferior frontal, midfrontal, superior frontal) and inferior parietal regions. In the inferior parietal region, habituation was more marked in the left than the right hemisphere. Right-handers showed greater habituation than did left-handers. There was no sex difference in global habituation, but males showed greater left whereas females showed greater right hemispheric habituation. The results suggest that habituation to the experimental setting has measurable effects on rCBF, which are differently lateralized for men and women. These effects are superimposed on task activation and are most pronounced in regions that have been implicated in attentional processes. Thus, regional decrement in brain activity related to habituation seems to complement attentional effects, suggesting a neural network for habituation reciprocating that for attention. PMID- 1618934 TI - Vibration-induced regional cerebral blood flow responses in normal aging. AB - Task-induced changes in regional CBF (rCBF) can be measured with positron emission tomography (PET) and provide a powerful tool to map brain function. Many studies using these techniques have investigated responses in healthy young subjects. Since many pathological conditions occur more commonly in older subjects, it is necessary to compare blood flow responses in these patients with appropriately age-matched controls. Furthermore, the effects of normal aging on such blood flow responses remain unknown. For both reasons, we designed this study to determine whether vibration-induced CBF responses change with advancing age in normals. CBF was measured with PET and bolus-administered H2(15)O in 26 subjects from 20 to 72 years old (mean = 39; SD = 19). Regional responses were identified by subtraction-image analysis. Left and right hand vibration produced consistent responses in contralateral primary sensorimotor area (PSA) and supplementary motor area (SMA). Response magnitudes were compared to age by linear regression. There were no substantial relationships between age and responses to vibration for PSA or SMA (PSA r = -0.28, p = 0.054; SMA r = -0.33, p = 0.13). Power analysis demonstrates a high degree of confidence (99.7% for PSA and 87% for SMA) for detecting at least a moderate correlation (r = 0.6) between response magnitude and age. We conclude that the rCBF responses to vibrotactile hand stimulation do not change with normal aging. PMID- 1618935 TI - Imaging muscarinic cholinergic receptors in human brain in vivo with Spect, [123I]4-iododexetimide, and [123I]4-iodolevetimide. AB - A method to image muscarinic acetylcholine receptors (muscarinic receptors) noninvasively in human brain in vivo was developed using [123I]4-iododexetimide ([123I]IDex), [123I]4-iodolevetimide ([123I]ILev), and single photon emission computed tomography (SPECT). [123I]IDex is a high-affinity muscarinic receptor antagonist. [123I]ILev is its pharmacologically inactive enantiomer and measures nonspecific binding of [123I]IDex in vitro. Regional brain activity after tracer injection was measured in four young normal volunteers for 24 h. Regional [123I]IDex and [123I]ILev activities were correlated early after injection, but not after 1.5 h. [123I]IDex activity increased over 7-12 h in neocortex, neostriatum, and thalamus, but decreased immediately after the injection peak in cerebellum. [123I]IDex activity was highest in neostriatum, followed in rank order by neocortex, thalamus, and cerebellum. [123I]IDex activity correlated with muscarinic receptor concentrations in matching brain regions. In contrast, [123I]ILev activity decreased immediately after the injection peak in all brain regions and did not correspond to muscarinic receptor concentrations. [123I]IDex activity in neocortex and neostriatum during equilibrium was six to seven times higher than [123I]ILev activity. The data demonstrate that [123I]IDex binds specifically to muscarinic receptors in vivo, whereas [123I]ILev represents the nonspecific part of [123I]IDex binding. Subtraction of [123I]ILev from [123I]IDex images on a pixel-by-pixel basis therefore reflects specific [123I]IDex binding to muscarinic receptors. Owing to its high specific binding, [123I]IDex has the potential to measure small changes in muscarinic receptor characteristics in vivo with SPECT. The use of stereoisomerism directly to measure nonspecific binding of [123I]IDex in vivo may reduce complexity in modeling approaches to muscarinic acetylcholine receptors in human brain. PMID- 1618936 TI - Measurement of radiotracer concentration in brain gray matter using positron emission tomography: MRI-based correction for partial volume effects. AB - Accuracy in in vivo quantitation of brain function with positron emission tomography (PET) has often been limited by partial volume effects. This limitation becomes prominent in studies of aging and degenerative brain diseases where partial volume effects vary with different degrees of atrophy. The present study describes how the actual gray matter (GM) tracer concentration can be estimated using an algorithm that relates the regional fraction of GM to partial volume effects. The regional fraction of GM was determined by magnetic resonance imaging (MRI). The procedure is designated as GM PET. In computer simulations and phantom studies, the GM PET algorithm permitted a 100% recovery of the actual tracer concentration in neocortical GM and hippocampus, irrespective of the GM volume. GM PET was applied in a test case of temporal lobe epilepsy revealing an increase in radiotracer activity in GM that was undetected in the PET image before correction for partial volume effects. In computer simulations, errors in the segmentation of GM and errors in registration of PET and MRI images resulted in less than 15% inaccuracy in the GM PET image. In conclusion, GM PET permits accurate determination of the actual radiotracer concentration in human brain GM in vivo. The method differentiates whether a change in the apparent radiotracer concentration reflects solely an alteration in GM volume or rather a change in radiotracer concentration per unit volume of GM. PMID- 1618937 TI - Effect of photic stimulation on human visual cortex lactate and phosphates using 1H and 31P magnetic resonance spectroscopy. AB - Previous animal and human studies showed that photic stimulation (PS) increased cerebral blood flow and glucose uptake much more than oxygen consumption, suggesting selective activation of anaerobic glycolysis. In the present studies, image-guided 1H and 31P magnetic resonance spectroscopy (MRS) was used to monitor the changes in lactate and high-energy phosphate concentrations produced by PS of visual cortex in six normal volunteers. PS initially produced a significant rise (to 250% of control, p less than 0.01) in visual cortex lactate during the first 6.4 min of PS, followed by a significant decline (p = 0.01) as PS continued. The PCr/Pi ratios decreased significantly from control values during the first 12.8 min of PS (p less than 0.05), and the pH was slightly increased. The positive P100 deflection of the visual evoked potential recorded between 100 and 172 ms after the strobe was significantly decreased from control at 12.8 min of PS (p less than 0.05). The finding that PS caused decreased PCr/Pi is consistent with the view that increased brain activity stimulated ATPase, causing a rise in ADP that shifted the creatine kinase reaction in the direction of ATP synthesis. The rise in lactate together with an increase in pH suggest that intracellular alkalosis, caused by the shift of creatine kinase, selectively stimulated glycolysis. PMID- 1618938 TI - Anoxia-induced changes in extracellular K+ and pH in mammalian central white matter. AB - In gray matter (GM), anoxia induces prominent extracellular ionic changes that are important in understanding the pathophysiology of this insult. White matter (WM) is also injured by anoxia but the accompanying changes in extracellular ions have not been studied. To provide such information, the time course and magnitude of anoxia-induced changes in extracellular K+ concentration ([K+]o) and extracellular pH (pHo) were measured in the isolated rat optic nerve, a representative central WM tract, using ion-selective microelectrodes. Anoxia produced less extreme changes in [K+]o and pHo in WM than are known to occur in GM; in WM during anoxia, the average maximum [K+]o was 14 +/- 2.9 mM (bath [K+]o = 3 mM) and the average maximum acid shift was 0.31 +/- 0.07 pH unit. The extracellular space volume rapidly decreased by approximately 20% during anoxia. Excitability of the rat optic nerve, monitored as the amplitude of the supramaximal compound action potential, was lost in close temporal association with the increase in [K+]o. Increasing the bath glucose concentration from 10 to 20 mM resulted in a much larger acid shift during anoxia (0.58 +/- 0.08 pH unit) and a smaller average increase in [K]o (9.2 +/- 2.6 mM). The increased extracellular glucose concentration presumably provided more substrate for anaerobic metabolism, resulting in more extracellular lactate accumulation (although not directly measured) and a greater acid shift. Enhanced anaerobic metabolism during anoxia would provide energy for operation of ion pumps, including the sodium pump, that would result in smaller changes in [K+]o. These effects were probably responsible for the observation that the optic nerve showed significantly less damage after 60 min of anoxia in the presence of 20 mM glucose compared to 10 mM glucose. Under normoxic conditions, increasing bath K+ concentration to 30 mM (i.e., well beyond the level shown to occur with anoxia) for 60 min caused abrupt loss of excitability during the period of application but minimal change in the amplitude of the compound action potential following the period of exposure. The anoxia-induced increase in [K+]o, therefore, was not itself directly responsible for irreversible loss of optic nerve function. These observations indicate that major qualitative differences exist between mammalian GM and WM with regard to anoxia-induced extracellular ionic changes. PMID- 1618939 TI - Regional cerebral L-[14C-methyl]methionine incorporation into proteins: evidence for methionine recycling in the rat brain. AB - The specific activity (SA) of free methionine was measured in plasma and in different regions of the rat brain at 15, 30, or 60 min after intravenous infusion of L-[14C-methyl]methionine. Within these time periods, an apparent steady state of labeled free methionine in plasma and in brain was reached. However, the brain-to-plasma free methionine SA ratio was found to be approximately 0.5, showing that an isotopic equilibrium between brain and plasma was not attained. This suggests the presence of an endogenous source of brain free methionine (likely originating from protein breakdown), in addition to the plasma source. The contribution of this endogenous source to the content of free methionine varies significantly among the different brain regions. Our results indicate that the regional rates of protein synthesis measured with L-[11C methyl]methionine using positron emission tomography would be underestimated, since the local fraction of brain methionine derived from protein degradation would not be considered. PMID- 1618940 TI - Chronic parasympathetic sectioning decreases regional cerebral blood flow during hemorrhagic hypotension and increases infarct size after middle cerebral artery occlusion in spontaneously hypertensive rats. AB - Regional cerebral blood flow (rCBF) during controlled hemorrhagic hypotension (140-20 mm Hg) was assessed 10-14 days after chronic unilateral sectioning of parasympathetic and/or sensory fibers innervating pial vessels in spontaneously hypertensive rats (SHR). rCBF was measured in the cortical barrel fields bilaterally by laser Doppler blood flowmetry. Immunohistochemistry of middle cerebral artery (MCA) whole mount preparations was used to verify the surgical lesion. During hemorrhagic hypotension, rCBF was equivalent on the two sides in shams, after selective sensory denervation, or in parasympathetically sectioned animals exhibiting small decreases (less than or equal to 30%) in immunoreactive vasoactive intestinal peptide (VIP)-containing fibers. After chronic parasympathetic denervation, decreases in perfusion pressure were accompanied by greater reductions in rCBF on the lesioned side; changes in vascular resistance were also attenuated on that side. The rCBF response to hypercapnia (PaCO2 50 mm Hg), however, was symmetrical and robust. To examine the effects of impaired neurogenic vasodilation on the pathophysiology of cerebral ischemia, infarct size was measured 24 h following tandem MCA occlusion in denervated animals. Infarction volume was larger after selective parasympathetic sectioning (sham, 156 +/- 27 vs. 196 +/- 32 mm3, respectively) but only in those denervated animals demonstrating greater than or equal to 40% decrease in immunoreactive VIP containing fibers within the ipsilateral MCA. Lower than expected blood flow/perfusion pressure in the cortex distal to an occluded blood vessel may relate the observed blood flow responses to the occurrence of larger cortical infarcts in parasympathetically denervated animals. If true, the findings suggest a novel role for neurogenic vasodilation in the pathophysiology of cerebral ischemia and in rCBF regulation within the periinfarction zone. PMID- 1618941 TI - The effect of hypothermia on transient middle cerebral artery occlusion in the rat. AB - We investigated the effect of moderate whole body hypothermia (30 degrees C) on transient middle cerebral artery occlusion (MCAO) in the rat. Male Wistar rats were subjected to 2 h of ischemia by inserting a suture into the lumen of the internal carotid artery and occluding the origin of the MCA. Experimental groups were (a) MCAO induced at 37 degrees C body temperature (n = 15); (b) 30 degrees C body temperature induced prior to ischemia and maintained for 2 h of MCAO and 1 h of reperfusion (n = 12); and (c) MCAO with regional brain and body temperatures measured in normothermic (n = 3) and hypothermic MCAO rats (n = 2). Histopathological evaluation was performed 96 h after reperfusion. All normothermic MCAO animals exhibited ischemic infarct involving the ipsilateral cortex and basal ganglia with infiltration of neutrophils, macrophages, and microvascular proliferation. Hypothermic MCAO animals exhibited minor ischemic damage ranging from selective neuronal injury to small focal areas of infarct with minimal inflammatory response. Our data demonstrate that transient ischemia induced by using the intra-arterial suture method to occlude the MCA results in a reproducible brain lesion and that moderate hypothermia has a profound protective effect on the brain injury after transient MCAO. PMID- 1618942 TI - Evoked neuronal activity accompanied by transmitter release increases oxygen concentration in rat striatum in vivo but not in vitro. AB - Dopamine and oxygen (O2) were measured in the caudate nucleus of anesthetized rats and in striatal slices during electrical stimulation. Simultaneous electrochemical detection of dopamine and O2 was accomplished with fast-scan cyclic voltammetry at a Nafion-coated carbon-fiber microelectrode. Stimulation of the medial forebrain bundle resulted in synaptic overflow of dopamine in the caudate nucleus. At the same time, O2 concentration increased in the extracellular fluid with two separate phases. The amplitude of the initial increase directly correlated with the frequency of the stimulus, with the time of maximum concentration reproducible across a range of frequencies. The second increase occurred at later times with a more random amplitude and with a broad, variable shape. Agents which blocked vasodilation affected both phases: atropine attenuated the initial increase, while the second feature was nearly absent after theophylline. Yohimbine and alpha-methyl-p-tyrosine did not affect the O2 responses. Local electrical stimulation of the slice preparation also resulted in dopamine overflow, but a prolonged decrease in O2 concentration accompanied this event. Striatal field stimulation in vivo produced changes in O2 concentration dependent on the relative position of the stimulating and working electrodes, but none of the responses resembled that seen in the caudate slice. Thus, while measurements in brain slices show O2 consumption as a result of stimulated neuronal activity, an apparent elevation of local cerebral blood flow during and after stimulation dominate the in vivo response. PMID- 1618944 TI - Regulation of cortical blood flow by the dorsal raphe nucleus: topographic organization of cerebrovascular regulatory regions. AB - We examined in rat: (1) the time-course and magnitude of change in cortical blood flow (CoBF) following electrical stimulation of the dorsal raphe nucleus (DRN) and (2) whether DRN lesions affect resting CoBF or the cerebrovascular response to CO2. Animals were anesthetized (chloralose), paralyzed, and artificially ventilated. The effect of stimulus frequency (1-200 Hz) and intensity (10-100 microA) on arterial pressure, heart rate, and CoBF was examined; lesions were made electrolytically. CoBF was measured using a laser-Doppler flowmeter with the probe placed extradurally over the parietal sensorimotor cortex. The DRN was computer reconstructed in three dimensions from Nissl stained coronal sections for localization of electrode placements. Brief stimuli (8 s; n = 6) elicited frequency and intensity-dependent increases in arterial pressure, heart rate, and CoBF. Sustained intermittent trains of stimuli of rostral DRN (200 Hz; 1 s on/1 s off; 70 microA) elicited a decrease (85 +/- 12% of baseline; n = 9) in CoBF (p less than 0.05) while stimulation in caudal DRN resulted in increased CBF (126 +/ 13% of baseline; n = 9). Phenylephrine infusion (0.1-1 microgram; i.v.; n = 8) increased arterial pressure and CoBF less than that elicited by brief DRN stimulation (p less than 0.05). DRN lesions did not affect resting CoBF (140 +/- 25 perfusion units (PU) before; 127 +/- 16 PU after DRN lesion; p greater than 0.05, n = 5) or mean arterial pressure (127 +/- 13 before; 120 +/- 11 after); nor did it affect the cerebrovascular response to change in arterial PCO2. Sustained intermittent stimulation of the DRN can evoke either increases or decreases in CoBF depending on the anatomical sublocalization. The DRN does not tonically maintain resting CoBF, nor participate in the cerebrovascular response to change in PCO2. PMID- 1618943 TI - Effect of 2-chloroadenosine on cerebrovascular reactivity to hypercapnia in newborn pig. AB - The effect of local administration of vasodilative concentrations of the adenosine receptor agonist 2-chloroadenosine (2-CADO) on the hyperemic responses of the pial and parenchymal microcirculations to graded hypercapnia was determined. The cranial window and brain microdialysis-hydrogen clearance techniques were utilized in two groups of isoflurane-anesthetized newborn pigs to measure changes in pial diameters and local CBF, respectively, in response to graded hypercapnia in the absence and presence of 2-CADO. Progressive size dependent dilations of pial arterioles [small = 41 +/- 7 microns (mean +/- SD), intermediate = 78 +/- 13 microns, and large = 176 +/- 57 microns in diameter] occurred in response to graded hypercapnia alone (PaCO2 = 58 and 98 mm Hg) and to superfusions of 2-CADO (10(-5) M) during normocapnia; the magnitude of the dilative response to each of these stimuli was inversely proportional to vessel size. When hypercapnia was induced concomitantly with 2-CADO superfusion, the dilative effects of each stimulus were directly additive. Similarly, local microdialysis infusion of 10(-5) M 2-CADO, which doubled CBF during normocapnia, did not affect the hyperemic response of the parenchymal circulation to graded hypercapnia (PaCO2 = 69 and 101 mm Hg). Our findings are consistent with the participation of adenosine in the mediation of cerebral hypercapnic hyperemia. If, however, adenosine is not involved in this dilative response, our results indicate that concomitant vascular and neuromodulatory actions induced by adenosine receptor stimulation do not affect the mechanism responsible for the hypercapnic hyperemic response. PMID- 1618945 TI - Rapid autoregulation of cerebral blood flow: a laser-Doppler flowmetry study. AB - The mechanisms underlying autoregulation of CBF were studied in 19 rabbits using laser-Doppler flowmetry. A cranial plexiglas window was chronically inserted in the skull with dental cement under general anesthesia. The animals then were reanesthetized 5-7 days later and subjected to aortic bleeding while CBF was measured with the probe placed on the window. In the first set of experiments, MABP was decreased (from 90 to 30 mm Hg) and was maintained constant for 1 min. During the first seconds, CBF followed the steep decrease of MABP. Then, CBF increased and reached a plateau within 3-13 s, depending on the severity of hypotension. Hyperemia occurred when blood was restored, and the CBF recovered from this posthypotensive hyperemia with a rapid phase (within 2 s) and a slow phase (total recovery within 1 min). The lower limit of autoregulation was found to be 40 mm Hg. An increase in CBF due to papaverine showed that vasodilation was not maximal below this limit. In the second set of experiments, the rabbits were subjected to four episodes of hypotension at 40 mm Hg each but of different durations (from 2-3 to 60 s). The posthypotensive hyperemia was not influenced by the duration of hypotension, but the time of the total recovery phase increased with the duration of hypotension. We conclude that there exist rapid adaptive mechanisms leading to autoregulation and that the vasodilation is not dependent upon the duration of hypotension. PMID- 1618947 TI - Changes in neuropeptide Y after experimental traumatic brain injury in the rat. AB - We utilized a model of fluid percussion (FP) brain injury in the rat to examine the hypothesis that alterations in brain neuropeptide Y (NPY) concentrations occur following brain injury. Male rats (n = 44) were subjected to FP traumatic brain injury. One group of animals (n = 38) was killed at 1 min, 15 min, 1 h, or 24 h after brain injury, and regional brain homogenates were analyzed for NPY concentrations using radioimmunoassay. A second group of animals (n = 6) was killed for NPY immunocytochemistry. Concentrations of NPY in the injured left parietal cortex were significantly elevated at 15 min post injury (p less than 0.05). No changes were observed in other brain regions. NPY-immunoreactive fibers were seen at 15 min post injury predominantly in the injured cortex and adjacent hippocampus. These temporal changes in NPY immunoreactivity, together with previous observations concerning posttraumatic changes in regional CBF in these same areas, suggest that an increase in region NPY concentrations after brain injury may be involved in part in the pathogenesis of posttraumatic hypoperfusion. PMID- 1618946 TI - Attenuated development of ischemic brain edema in vasopressin-deficient rats. AB - Brain edema formation was investigated in the vasopressin-deficient Brattleboro rat using a middle cerebral artery occlusion model of early ischemic injury. Water and sodium accumulation after 4 h of ischemia were attenuated 36 and 20%, respectively, in the Brattleboro strain as compared to the control Long-Evans strain. This effect was independent of differences in animal size and state of hydration. In addition, measurements of cerebral blood flow indicated that Brattleboro and Long-Evans rats had equal levels of ischemia following middle cerebral artery occlusion. Systemic treatment of Brattleboro rats with vasopressin normalized their serum electrolyte concentrations and osmolarity but did not alter sodium or water accumulation in the ischemic brain. In contrast, intraventricular administration of vasopressin in Brattleboro rats increased edema formation to that seen in control rats. The reduced water and sodium accumulation in Brattleboro rats subjected to middle cerebral artery occlusion may be related to alterations in blood-brain barrier permeability since the blood to-brain sodium flux was 36% less in the ischemic tissue of the Brattleboro as compared to the Long-Evans strain. These results support the hypothesis that central vasopressin is a regulator of brain volume and electrolyte homeostasis. Furthermore, our findings suggest a role for central vasopressin in the development of ischemic brain edema. PMID- 1618948 TI - The endothelium-dependent effects of thimerosal on mouse pial arterioles in vivo: evidence for control of microvascular events by EDRF as well as prostaglandins. AB - Thimerosal causes synthesis and/or release of both endothelium-derived relaxing factor (EDRF) and prostaglandins from conductance vessels in vitro. We tested its effects and mechanism of action on mouse pial arterioles in vivo using intravital microscopic techniques. Topical thimerosal dilated pial arterioles. This effect was eliminated by endothelial injury produced by a laser/Evans blue technique. Dilation was also eliminated by topical L-NMMA, a reported inhibitor of EDRF synthesis. Topical thimerosal also reduced the incidence of platelet adhesion/aggregation ("capture") at a site of minimal endothelial damage. This effect was eliminated by L-NMMA pretreatment. The ability of thimerosal to dilate arterioles was eliminated not only by treatments thought to eliminate synthesis/release of EDRF, but also by cyclooxygenase inhibitors. However, inhibition of platelet adhesion/aggregation was not affected by cyclooxygenase inhibition. Thimerosal significantly increased production of prostaglandin E2 recovered from a closed cranial window. We conclude that the dilating effects of thimerosal on diameter require two endothelium-derived agents: EDRF and one or more prostaglandins acting in concert. However, the inhibiting effect of thimerosal on local platelet adhesion/aggregation appears to be caused only by an increase in EDRF at the injured site. PMID- 1618949 TI - Characterization of an aminopeptidase in cerebrospinal fluid. Structure elucidation of enzyme hydrolysis products of synthetic methionine-enkephalin by reversed-phase high-performance liquid chromatography and mass spectrometry. AB - An aminopeptidase was found in canine cerebrospinal fluid via the presence of two products: Y, which has an [M + H]+ ion at m/z 182; and GGFM, which has an [M + H]+ ion at m/z 411. The linked scan at a constant ratio of the magnetic field to the electric field of the GGFM [M + H]+ ion at m/z 411 generates product ions at m/z 120, 150, 266, 297, 354, 357, and 411. That aminopeptidase was bestatin sensitive (BSAP = bestatin-sensitive aminopeptidase), and had a half-time for disappearance of 60 min, maximum velocity of 1.08 nmol ml-1 min-1, and Michaelis constant of 0.26 nM. PMID- 1618950 TI - Analysis of conjugated bile acids by packed-column supercritical fluid chromatography. AB - A rapid method has been developed for the simultaneous separation of the polar glycine- and taurine-conjugated bile acids by packed-column supercritical fluid chromatography. Samples were analysed on a cyanopropyl-bonded silica column with ultraviolet detection at 210 nm and carbon dioxide modified with methanol as the mobile phase. The influence of the stationary phase, modifier concentration, temperature, column pressure and modifier identity on retention was also studied. This new chromatographic method is applicable to the assay of conjugated bile acids in duodenal bile samples from patients with hepatobiliary diseases. PMID- 1618951 TI - High-performance liquid chromatographic method to resolve and determine lipopolysaccharide sub-groups of Escherichia coli endotoxin in isolated perfused rat liver perfusate. AB - A high-performance liquid chromatographic method was developed for resolving heterogeneous preparations of fluorescently labelled endotoxin derived from Escherichia coli (Serotype 0111:B4) into separate lipopolysaccharide sub-groups. The endotoxin was chromatographed on an analytical gel permeation column using a mobile phase of acetonitrile (20%, v/v) and 100 mM phosphate buffer (pH 7.75). Four fluorescent peaks were resolved, representing sub-groups of markedly different molecular sizes. Three of the four sub-groups contained the core polysaccharide 2-keto-3-deoxyoctonate, confirming that they contained lipopolysaccharide. Fluorescein isothiocyanate (FITC)-labelled endotoxins derived from Vibrio cholerae and Salmonella minnesota chromatographed using the same system eluted with distinctly different patterns of peaks from each other and from E. coli. Extraction of E. coli FITC-endotoxin from a buffer solution using a phenol-diethyl ether method and subsequent chromatography allowed the determination of three of the four fluorescent sub-groups over the concentration range 1-15 micrograms/ml. PMID- 1618952 TI - Optimization of high-performance liquid chromatographic assay for catecholamines. Determination of optimal mobile phase composition and elimination of species dependent differences in extraction recovery of 3,4-dihydroxybenzylamine. AB - This paper describes the application of a window diagram technique to optimize the four components of eluent (sodium acetate, sodium heptanesulfonate, acetonitrile and pH adjusted by monochloroacetic acid), for complete separation of five catecholamine compounds and the internal standard (3,4 dihydroxybenzylamine, DHBA). In addition, studies were performed to address the problem of the variable recovery of DHBA from dog plasma due to a time-dependent loss of DHBA. We found that this phenomenon can be prevented by pH adjustment prior to addition of DHBA, allowing development of an accurate high-performance liquid chromatographic assay for plasma catecholamines in dogs. PMID- 1618953 TI - Reversed-phase high-performance liquid chromatographic tryptic digest peptide map comparisons of monoclonal antibodies to human tumor necrosis factor. AB - An automatic computer technique was used to compare the retention times and ultraviolet spectra of sixty-two peaks in peptide maps of three monoclonal antibodies against human tumor necrosis factor (TNF) and one monoclonal antibody against recombinant factor VIII. The anti-TNF monoclonal, B6, which has an overlapping epitope with the anti-TNF monoclonal, A10G10, had a 90% peak match with A10G10. The anti-TNF monoclonal, A6, with a different epitope to TNF than A10G10, had only a 60% peak match. The A6 match to A10G10 was similar to the 50% peak match of the anti-factor VIII monoclonal with A10G10. The results of this study suggest that peptide mapping can be used as a quantitative characterization technique for comparing monoclonal antibodies. PMID- 1618954 TI - Large-scale purification and characterization of recombinant tick anticoagulant peptide. AB - Recombinant tick anticoagulant peptide (r-TAP), a potent and specific inhibitor of blood coagulation factor Xa, was purified to greater than 99% homogeneity at the multi-gram scale. Genetically engineered yeast secreted 200-250 mg/l of the heterologous protein into the medium. Cells were separated from broth by diafiltration and purification was done by two chromatographic steps, both conducive to operation on a large scale. Analysis of the purified protein by several methods indicated that it was greater than 99% homogeneous and no incompletely processed or truncated proteins were detected. Physico-chemical characterization data of r-TAP show that it exists as a monomer in solution and no evidence of post-translational modification was observed. The purified protein was fully active in inhibiting human coagulation factor Xa. PMID- 1618955 TI - Interactions of human alkaline phosphatase isoenzymes with triazine dyes using affinity partitioning, affinity chromatography and difference spectroscopy. AB - Aqueous two-phase systems consisting of dextran, polyethylene glycol and dye liganded polyethylene glycol were employed to investigate the affinity partitioning behaviour of isoenzymes of human alkaline phosphatase. Whereas in the system without a dye ligand the partition coefficients of the isoenzymes from human intestine and placenta were identical, the isoenzyme from human liver showed a significantly lower partition coefficient under the same conditions. After addition of dye-liganded polyethylene glycol two groups of dyes possessing substantial affinities to the isoenzymes were found. One, represented by Procion Yellow HE-3G, interacts specifically with the active centre of the isoenzymes. Differences in the affinity of the isoenzymes towards the individual dye ligands are caused only by the carbohydrate content, especially by the terminal sialic acid residues. The other group of dye ligands, represented by Procion Navy MX-RB, binds obviously in a more complex fashion involving other binding sites, which are only present in alkaline phosphatase of human liver. Procion Navy MX-RB was found to function as a suitable affinity ligand for the separation of human liver alkaline phosphatase from the other isoenzymes. Differences in the primary structure of two allelic forms of human placental alkaline phosphatase [(SS) and (F)] are not recognized in aqueous two-phase systems with or without dye-liganded polyethylene glycol. PMID- 1618956 TI - Subtraction method for the high-performance liquid chromatographic measurement of plasma adenosine. AB - The measurement of plasma adenosine with traditional high-performance liquid chromatographic techniques is difficult because of its nanomolar concentration, its short half-life in blood, and because of the difficulty in isolating adenosine from interfering peaks in the chromatogram. To prevent loss of adenosine in the blood sample, a "stop solution" is used to prevent enzymatic degradation and cellular uptake. Peak-shifting techniques on fractionated samples to measure adenosine derivatives have been used in the past to avoid interfering peaks in the chromatogram. A new method has been developed by which nanomolar levels of plasma adenosine can be accurately measured despite co-eluting peaks in the chromatogram. In this method, plasma samples are collected with a stop solution, processed, and divided. Adenosine deaminase is added to part of the sample to form a blank. A computer program subtracts the blank chromatogram from the paired unknown, and the result is compared to adenosine standards prepared from the blank and subtracted in a similar fashion. With this subtraction method, the overall recovery of physiological concentrations of adenosine was 89% from dog blood, and the average coefficient of variation was 12%. In summary, the subtraction method of plasma adenosine measurement offers good recovery, reproducibility, and the ability to quantify low levels of adenosine despite interfering peaks in the chromatogram. PMID- 1618957 TI - High-performance liquid chromatographic determination of 3-hydroxypyridinium derivatives as new markers of bone resorption. AB - Hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are intermolecular cross linking amino acids of collagen and their urinary excretion reflects bone resorption. An isocratic high-performance liquid chromatographic assay using a reversed-phase column with a prefractionation step and fluorescence detection was developed. The accuracy and reproducibility were assessed by loading experiments and by double analysis of urinary samples. The recoveries after various loads were above 90% for HP and between 87 and 94% for LP, with an intra-assay relative standard deviation (R.S.D.) of 5% for HP and 8% for LP. The inter-assay R.S.D.s were 8% for HP and 12.4% for LP. The fasting and 24-h urinary excretions of HP and LP were measured in 40 healthy subjects (mean age 35 years) of both sexes. There was no difference between males and females. Mean adult normal values were 33.6 +/- 8.1 pmol/mumol creatinine for HP and 7.0 +/- 2.5 pmol/mumol creatinine for LP in morning fasting urine and 2-.9 +/- 7.0 pmol/mumol creatinine for HP and 5.8 +/- 1.9 pmol/mumol creatinine for LP after 24-h urinary collection. HP and LP excretions were significantly higher in morning fasting urine than in 24-h collections, in agreement with the physiological circadian rythm of bone resorption. This simplified and optimized procedure is a good method for the determination of pyridinolines and should be useful for the evaluation of bone resorption. PMID- 1618958 TI - Separation and sensitive determination of i-urobilin and 1-stercobilin by high performance liquid chromatography with fluorimetric detection. AB - i-Urobilin and 1-stercobilin were separated by high-performance liquid chromatography on a reversed-phase octadecylsilane-bonded column and detected fluorimetrically through formation of phosphor with zinc ions in the eluent. The separation and the intensity of the fluorescence response were affected by concentrations of zinc acetate and sodium borate buffer, pH and methanol content in the eluent. The optimal eluent used consisted of 0.1% zinc acetate in 75 mM boric acid buffer (pH 6.0)-methanol (25:75). The detection limit was 0.2 microgram/l for both i-urobilin and 1-stercobilin (signal-to-noise ratio 2), which makes the method 250-2500 times more sensitive than conventional methods. PMID- 1618959 TI - Novel solid-state fluorodensitometric method for the determination of haptens in protein-hapten conjugates. Demonstration with a toxic glycoside of Cleistanthus collinus. AB - A method is reported for the solid-state fluorodensitometric determination of haptens in hapten-protein conjugates. The applicability of the method is shown using the bovine serum albumin conjugate of cleistanthin B, a toxic glycoside of the plant Cleistanthus collinus. This non-destructive technique, which is relatively simple, sensitive, rapid and versatile, can be used for the determination of protein conjugates of fluorogenic haptens. PMID- 1618960 TI - Fully automated determination of a new anthracycline N-l-leucyldoxorubicin and six metabolites in plasma by high-performance liquid chromatography with on-line sample handling. AB - N-l-Leucyldoxorubicin (Leu-Dox) was developed as a prodrug of doxorubicin (Dox) in order to diminish the cardiotoxic side-effect associated with repeated anthracycline treatment. To study the pharmacokinetics of Leu-Dox, Dox and other metabolites a sensitive and selective assay was needed. Leu-Dox and six of its known metabolites were extracted from plasma using an in-line reversed-phase precolumn (40-50 microns C8 particles). The trapped analytes were subsequently flushed to the analytical column (3 microns C18) using 0.5 ml of phosphate buffer (pH 3.5)-acetonitrile (2:1, v/v), which also served as the isocratic mobile phase. Within 12 min, a clean baseline-resolved chromatogram is obtained by fluorescence detection. Recoveries were almost quantitative and highly reproducible, with standard deviations less than or equal to 5.4% and less than or equal to 2.7% at spiked concentrations of 10 and 100 nM. Using 300 microliters of plasma, detection limits ranged from 0.3 to 0.8 nM at a signal-to-noise ratio of 3. The calibration curves were linear from 1 to 300 nM (r2 greater than or equal to 0.999) for each of the seven compounds. The between-day accuracy was in the range 91-99% and 99-105% at 10 and 100 nM, respectively, with standard deviations of 1-4%. Application of the assay to the analysis of plasma from patients after administration of Leu-Dox proved successful. PMID- 1618961 TI - Determination of yohimbine and its two hydroxylated metabolites in humans by high performance liquid chromatography and mass spectral analysis. AB - The existence of at least two metabolites of yohimbine (YO) in humans is demonstrated. Combined high-performance liquid chromatographic (HPLC), NMR and mass spectral analyses permitted them to be identified as hydroxylated metabolites at the C-10 and C-11 positions. A normal-phase HPLC method allowing the simultaneous determination of YO and its main metabolite, 11-hydroxyyohimbine (11-OHYO), in biological samples is described. This assay was performed using a LiChrosorb Si 60 column and a mobile phase consisting of 0.02 M sodium acetate (pH 5)-methanol (5:95, v/v) at a flow-rate of 1 ml/min. Detection was achieved by a fluorimetric method (excitation at 280 nm and emission at 320 nm). The extraction yields of YO, 10-OHYO and 11-OHYO from plasma were 91.8, 45.3 and 17.8%, respectively, and their respective within-day reproducibilities were 3.8, 1.4 and 5.9%. The between-day reproducibility for YO at the concentrations of 1 and 10 ng/ml were 8.9 and 6.4%, respectively. The accuracy of the method for YO at concentrations of 1 and 10 ng/ml were 5.1 and 2.3%, respectively. The limits of determination of YO, 10-OHYO and 11-OHYO were 0.1, 0.5 and 1 ng/ml, respectively. The method was used in bioavailability study of YO following oral and intravenous administration in humans. PMID- 1618962 TI - Biodetermination of N-(deacetyl-O-4-vinblastoyl-23)-L-tryptophan, a metabolite of vintriptol, by high-performance liquid chromatography with fluorescence detection. AB - The determination of N-(deacetyl-O-4-vinblastoyl-23)-L-tryptophan (vintriptol acid, VtrpA), a metabolite of the investigational semi-synthetic vinca alkaloid vintriptol [N-(deacetyl-O-4-vinblastoyl-23)-L-ethyltryptophan, VtrpE], in plasma and urine samples is described. Sample pretreatment included liquid-liquid extraction of the buffered (pH 5.0) biological samples with chloroform-2-propanol (95:5, v/v). The analyses were performed by ion-exchange high-performance liquid chromatography on normal-phase silica with fluorescence detection. The assay was applied to the analysis of samples from cancer patients who had been treated with VtrpE in a phase I clinical study. VtrpA was found to be a principal metabolite of VtrpE with up to 1.2% of the administered dose excreted in the urine. PMID- 1618963 TI - Determination of fumonisin B1 in plasma and urine by high-performance liquid chromatography. AB - Fumonisin B1 (FB1), the major compound of the newly described fumonisin mycotoxins, has been shown to be the causative agent of the animal diseases leukoencephalomalacia in horses and pulmonary oedema in pigs. Whereas previous analytical methods have dealt with the determination of FB1 in feed and foodstuffs, this report for the first time details methods for FB1 determination in the physiological fluids, plasma and urine. The methods involve solid-phase anion-exchange clean-up, precolumn derivatisation with o-phthaldialdehyde and reversed-phase high-performance liquid chromatography with fluorescence detection. These methods were shown to be sensitive (detection limit around 50 ng ml-1), reproducible (relative standard deviation on six replicates less than 5%) and accurate (recoveries on spiked blank samples above 85%). PMID- 1618964 TI - Simultaneous determination of chloroquine and its three metabolites in human plasma, whole blood and urine by ion-pair high-performance liquid chromatography. AB - A method was developed for the separation and measurement of chloroquine and three metabolites (desethylchloroquine, bisdesethylchloroquine and 4-amino-7 chloroquinoline) in biological samples by ion-pair high-performance liquid chromatography with UV detection. The method uses 2,3-diaminoaphthalene as an internal standard and provides a limit of detection between 1 and 2 ng/ml for chloroquine and its metabolites. The assay was linear in the range 12.5-250 ng/ml and the analytical recovery and reproducibility were sufficient. The assay was applied to the analysis of biological samples from a patient undergoing chloroquine chemoprophylaxis and a patient who had ingested chloroquine in a suicide attempt. PMID- 1618965 TI - High-performance liquid chromatographic procedure for the determination of tiagabine concentrations in human plasma using electrochemical detection. AB - A sensitive and precise high-performance liquid chromatographic procedure has been developed for the measurement of tiagabine concentrations in human plasma. Isolation of tiagabine and the internal standard was achieved using solid-phase extraction on disposable C8 columns. Separation was performed on a C18 analytical column using a mobile phase containing sodium octanesulfonate. The effluent was monitored with coulometric electrochemical detection at ca. + 0.76 V. The workup procedure recovered more than 95% of tiagabine from plasma. Standard curves were linear over the concentration range 0-500 ng/ml. The precision of the method was good: coefficients of variation were typically less than 5% for concentrations as low as 8 ng/ml and although they were higher at concentrations less than 8 ng/ml, they remained within acceptable limits (less than 17%) for concentrations as low as the limit of quantitation (2 ng/ml using a l-ml plasma sample). The stability of tiagabine in plasma was excellent, with no evidence of degradation after 23 h at room temperature or 2 months at -20 degrees C. PMID- 1618966 TI - Determination of the tricyclic compound adosupine and its three metabolites in plasma and brain of rat using high-performance liquid chromatography. AB - An analytical method for the detection in biological samples of the novel tricyclic compound adosupine (10-acetoamido-5-methyl-5,6-dihydro-11H dibenzo[b,e]azepin-6 ,11-dione), which is capable of influencing various forms of urinary bladder hyperreflexia has been developed using high-performance liquid chromatography with UV detection. Liquid-liquid extraction was used to isolate the parent compound, three metabolites and an analogue (added as internal standard) from plasma and brain of rat. Adosupine was well separated from its three metabolites with 0.01 M disodium hydrogenphosphate-acetonitrile-methanol nonylamine (59.986:38:2:0.014) at pH 4.5 as mobile phase using a C18 reversed phase column. The standard curves were linear in the range 50-5000 ng/ml (or ng/g) for adosupine and metabolites in both plasma and brain. The between- and within-assay variations for high and low concentrations of the parent compound and the three metabolites were 8.2-14%. In the range 50-5000 ng/ml (or ng/g) the accuracy of the method was satisfactory, with the relative error always lower than 10%. Analytical recoveries of added adosupine and the three metabolites were higher than 82%. The method has been applied successfully, to investigate the pharmacokinetics of the drug and its distribution in the central nervous system of rats. PMID- 1618967 TI - Bioanalysis of some anthracyclines in human plasma by capillary electrophoresis with laser-induced fluorescence detection. AB - A rapid method for the determination of daunorubicin, doxorubicin and epirubicin in human plasma is described. Samples are pretreated and concentrated by liquid liquid extraction with chloroform and back-extraction into phosphoric acid, respectively. This pretreatment results in a sample matrix of low ionic strength in comparison with the electrophoresis buffer, permitting a 20-30-fold increase in the injected amount by zone sharpening when electrokinetic injection is applied. Analyte interaction with the capillary wall is prevented by using high acetonitrile contents in the electrophoresis buffer, which results in reproducible migration times and highly efficient separations. Laser-induced fluorescence detection provides an extremely sensitive and selective method without detectable biological interferences. The limit of determination of daunorubicin, epirubicin and doxorubicin in plasma ranges from 125 to 250 pg/ml. PMID- 1618968 TI - Analysis of pipecolic acid in biological fluids using capillary gas chromatography with electron-capture detection and [2H11]pipecolic acid as internal standard. AB - A sensitive and accurate stable isotope dilution assay was developed for the measurement of pipecolic acid in body fluids using capillary gas chromatography with electron-capture detection. The method utilizes [2H11]pipecolic acid as the internal standard. Sample preparation consisted of derivatization in aqueous solution (pH 11.5) of the amine moiety with methyl chloroformate to the N methylcarbamate, followed by acidic ethyl acetate extraction at pH less than or equal to 2 and further derivatization of the carboxyl moiety with pentafluorobenzyl bromide, the excess of which was removed by solid-phase extraction. Control values have been determined in the plasma of at-term infants, age greater than 1 week (n = 21, mean = 1.36 microM, range = 0.47-3.27 microM). The utility of the method was demonstrated by quantitating pipecolic acid in biological fluids derived from patients with peroxisomal disorders. The method was validated against an established electron-capture negative ion mass fragmentographic technique. PMID- 1618969 TI - Measurement of histamine in rat bronchoalveolar lavage fluid by high-performance cation-exchange chromatography coupled with post-column derivatization to o phthaldialdehyde. AB - To better define involvement of mast cell derived mediators in the pulmonary response to fibrogenic dusts, a rapid and accurate method was required to analyze samples of bronchoalveolar lavage fluid for histamine. Samples of rat lung lavage were analyzed for histamine via high-performance cation-exchange chromatography coupled with post-column derivatization with o-phthaldialdehyde. The fluorescent derivative could be detected to ca. 1 ng/ml of lavage. Recoveries averaged 94.2% with an average relative standard deviation of +/- 5.3%. There were no correlations between amount or fibrogenicity of inhaled dust and subsequent release of histamine into lavage fluid. PMID- 1618970 TI - Determination of endothelin-converting enzyme activity by high-performance liquid chromatography-on-line radioactive flow monitoring. AB - A rapid method to investigate the metabolism of 125I-labelled or non-labelled human big endothelin to endothelin-1 by reversed-phase high-performance liquid chromatography (HPLC) and on-line radioactive flow monitoring and/or ultraviolet detection was developed. Samples were processed by solid-phase extraction (average recovery 70-80% for non-labelled and 20-25% for 125I-labelled big endothelin and endothelin-1) followed by HPLC analysis (total analysis time 20 min). The method was successfully employed to monitor the conversion of big endothelin to endothelin-1 by various blood-borne cells, such as human polymorphonuclear leukocytes or monocytes/macrophages. PMID- 1618971 TI - Gas chromatographic determination of urinary phenol conjugates after acid hydrolysis/extractive acetylation. AB - Phenolic metabolites of inhaled aromatic solvent vapours were liberated by acid hydrolysis of their urinary conjugates. Steam distillation enhanced by salting out with MgSO4 gave good recoveries. After extractive acetylation, the derivatives of all cresols and xylenols were completely separated on a Se-54 capillary column. The overall recoveries of urinary phenols relative to the internal standard, 3-chlorophenol, were in the range 92-99%. PMID- 1618972 TI - Microanalytical high-performance liquid chromatographic assay for cefpirome in human milk and urine. AB - To permit the characterization of cefpirome disposition in lactating females, a previously published high-performance liquid chromatographic (HPLC) method for determining the drug in serum was adapted for use with milk and urine. This automated, microanalytical technique requires 50 microliters of biological matrix, which is subjected to an isopropanol extraction. Chromatography was accomplished using a microbore HPLC system, a reversed-phase C18 column and a mobile phase of 0.3% triethylamine in water (pH 5.1). Cefpirome and the internal standard (beta-hydroxypropyltheophylline) were monitored using UV detection at 240 nm and had retention times of 2.84 and 5.05 min, respectively. The method was linear up to 500 mg/l for both matrices and had a limit of detection of 0.6 mg/l. The interday variation (relative standard deviation) at concentrations of 5.0, 50.0 and 500.0 mg/l was consistently less than 5% in both urine and breast milk. The method was found to be free from interference by other commonly administered medications and readily adaptable for use in clinical investigations. The ease of sample preparation, small sample volume requirement, short chromatographic time, apparent lack of interferences, analytical sensitivity and high precision and accuracy make this method ideal for use in pharmacokinetic investigations involving the determination of cefpirome in human milk and urine. PMID- 1618973 TI - High-performance liquid chromatographic method for the simultaneous determination of monoethylglycinexylidide and lignocaine. AB - An accurate and sensitive high-performance liquid chromatographic method with UV detection was developed for the simultaneous measurement of monoethylglycinexylidide (MEGX) and lignocaine in human plasma and serum, using organic solvent extraction and trimethoprim (TMP) as an internal standard. The mean recoveries for MEGX, TMP and lignocaine were 86.1 +/- 3.7, 98.3 +/- 1.8 and 77.0 +/- 4.7%, respectively (n = 6). The relative standard deviations for MEGX concentrations of 10 and 200 ng/ml were less than 4% and for lignocaine concentrations of 200 and 1200 ng/ml they were less than 8%. PMID- 1618974 TI - Automated determination of disopyramide and N-monodealkyldisopyramide in plasma by reversed-phase liquid chromatography with a column switching system. AB - A rapid and simple column liquid chromatographic method involving a column switching system for the determination of disopyramide and its N-monodealkyl metabolite (NMD) in plasma is described. The deproteinized plasma is applied to an automated system. Purification and concentration were performed using a precolumn connected to a six-position valve; analytical separation was done on line using a cyano reversed-phase column with a mobile phase consisting of 10 mmol/l trimethylamine (pH 2.5, adjusted with phosphoric acid)-acetonitrile tetrahydrofuran (78:20:2, v/v/v). Absorbance was measured at 265 nm, with a minimum detectable amount of disopyramide and NMD of 0.1 micrograms/ml. The method can be applied to drug monitoring and pharmacokinetic studies. PMID- 1618975 TI - Assay of protein drug substances present in solution mixtures by fluorescamine derivatization and capillary electrophoresis. AB - A method is described to enhance the resolution and detection sensitivity of proteins, peptides, and amino acids in capillary electrophoretic analysis of solution mixtures. The method consists of derivatizing the analytes with fluorescamine, which is normally used as a fluorogenic reagent for compounds containing a reactive primary amine functional group, and then using the derivative as an ultraviolet chromophore to enhance detection sensitivity (measured at 280 nm) in capillary electrophoresis. The results demonstrated a significant improvement in the separation and detection sensitivity of the derivatized analytes as compared to their underivatized counterparts. The use of chromophores, such as fluorescamine, in capillary electrophoresis facilitates the analysis of components of solution mixtures, such as pharmaceutical formulations, that could not be resolved and/or detected by conventional capillary electrophoresis procedures. PMID- 1618976 TI - Evaluation of restricted access media for high-performance liquid chromatographic analysis of sulfonamide antibiotic residues in bovine serum. AB - Three commercially-available high-performance liquid chromatographic columns packed with restricted access media were evaluated for suitability in multi residue direct injection analysis at the ng/ml level. The internal surface reversed-phase and shielded hydrophobic phase columns were not sufficiently retentive to separate all analytes from the tail of the matrix peak. Coelution of some of the analytes was also observed with these columns. The semi-permeable surface column was significantly more retentive and selective, providing good separation of analyte and matrix peaks. With this column, an analytical protocol requiring no organic solvents was developed for the assay of six sulfonamides at a detection limit of 25 ng/ml. PMID- 1618977 TI - Simultaneous determination of amounts of major phospholipid classes and their fatty acid composition in erythrocyte membranes using high-performance liquid chromatography and gas chromatography. AB - A method for the simultaneous determination of amounts of major phospholipid classes and their fatty acid composition in erythrocyte membranes is described. The method consists in extraction of phospholipids from erythrocyte membranes, separation of phospholipid classes by high-performance liquid chromatography, methylation of phospholipids and determination of phospholipid-bound fatty acids by capillary gas chromatography. The amounts of phospholipid classes are calculated from the total weight of phospholipid-bound fatty acids and their average molecular weights. The method was applied to erythrocytes from rats. The results show that the method is reproducible and is useful for the determination of amounts of phospholipid classes and their fatty acid composition in small blood samples. PMID- 1618978 TI - High-performance hydrophobic interaction chromatography of proteins on reversed phase supports coated with non-ionic surfactants of polyoxyethylene type. Purification of a fungal aspartic proteinase. AB - On coating reversed-phase supports with polyoxyethylene-type non-ionic surfactants, proteins are no longer retained on such supports at moderate or low ionic strength, but they are retained at high ionic strength and can be desorbed by a decreasing ionic strength gradient. These reversibly modified supports were used for hydrophobic interaction chromatography (HIC). The proteins probably interact with the polyoxyethylene tail of the non-ionic surfactant while the hydrophobic part of the surfactant anchors the surfactant to the reversed-phase support by interactions with its alkane coverage. Although the interactions between non-ionic surfactant and reversed-phase support are non-covalent and the HIC mobile phases contained no surfactant, the modified columns were stable and could be used repeatedly. A surfactant-modified reversed-phase column provided a rapid, efficient, one-step purification of a fungal aspartic proteinase from a commercial crude preparation. PMID- 1618979 TI - On-line continuous-flow dialysis thermospray tandem mass spectrometry for quantitative screening of drugs in plasma: rogletimide. AB - The application of a continuous-flow dialysis system, consisting of a membrane dialyser and a trace enrichment column, in on-line combination with tandem mass spectrometry via a thermospray interface is described. The method is applied to the quantitation of drugs in complex biological matrices containing macromolecular interferences. The potential of the method is demonstrated by the quantitative analysis of the anti-cancer drug rogletimide in the plasma of patients after treatment. PMID- 1618980 TI - High-performance liquid chromatographic separation of molecular species of neutral phospholipids. AB - Molecular species of neutral phospholipids, phosphatidylcholine (PC) and phosphatidylethanolamine (PE), were resolved by reversed-phase high-performance liquid chromatography (HPLC) using mobile phases of acetonitrile-methanol-water containing tetraalkylammonium phosphates (TAAPs). Competitive interactions of TAAPs and analyte solutes with a reversed-phase HPLC column resulted in reduced retention of PC or PE with concomitant increase in detection sensitivity. The chromatographic data for PC and PE were distinctly different from those for negatively charged phospholipids where ion-pair retention mechanisms prevailed. While PC (or PE) components eluted at longer retention times with a larger size of TAAP, an increase in the TAAP concentration invariably caused a decrease in phospholipid retention times. Optimization of HPLC conditions by using high concentrations (25-100 mM) of tetramethylammonium phosphate in acetonitrile methanol-water (70:22:8) facilitated elution of components with improved peak symmetry. HPLC separations of neutral phospholipids derived from animal sources were more complex than those from soybeans. PMID- 1618981 TI - Analysis of sterol esters from alga and yeast by high-performance liquid chromatography and capillary gas chromatography-mass spectrometry with chemical ionization. AB - Sterol esters from the green alga Chlorella kessleri and the yeast Saccharomyces cerevisiae were analysed by tandem high-performance liquid chromatography (HPLC HPLC). Non-polar lipids were separated by normal-phase HPLC into individual classes and the fraction of sterol esters was subsequently separated by reversed phase HPLC into intact molecular species. Further separation and identification of the fractions after HPLC were effected by capillary gas chromatography-mass spectrometry (cGC-MS) with positive and/or negative chemical ionization. A technique consisting of direct injection of the sample after its passage through the detector into the on-column injector of the gas chromatograph was used to transfer the sample from HPLC-HPLC to cGC-MS. By means of this method it was possible to demonstrate more than 30 sterols in both the alga and the yeast, and more than 20 new sterol esters were detected. PMID- 1618982 TI - Simultaneous assay for amatoxins and phallotoxins in Amanita phalloides Fr. by high-performance liquid chromatography. AB - A reversed-phase high-performance liquid chromatographic method is described that allows the simultaneous determination of up to eight amatoxins and phallotoxins. The method identifies both neutral toxins (alpha- and gamma-amanitin, phalloidin, phallisin and phalloin) and acidic toxins (beta-amanitin, phallacidin and phallisacin). Toxins were separated, identified and determined by gradient elution with 0.02 M aqueous ammonium acetate-acetonitrile and simultaneous monitoring of the absorbances at 214 and 295 nm. The assay was successfully applied to the analysis of the toxins in a crude extract of Amanita phalloides. The limit of detection for each toxin was 10 ng/ml of extraction medium. The assay was further validated by analysing the toxin content in Galerina marginata, a species containing only amatoxins. This relatively simple method should be suitable for the detection of amatoxins and phallotoxins in almost any species of mushrooms. PMID- 1618983 TI - Isolation of Der pI, the Dermatophagoides pteronyssinus major mite allergen, from a crude mite culture extract, purification by ion-chromatography, and comparison between the material obtained and a cDNA-coded Der pI. AB - A high degree of purity is a prerequisite for an allergen preparation to be suitable for clinical diagnosis and therapy. A pure allergen can easily be obtained from a crude mite culture extract by using an immunosorbent prepared with highly specific monoclonal antibodies or from a cDNA-coded material. However, up to now none of these methods has been performed on a process scale. Here large-scale purification is defined as a process in which a crude Dermatophagoides pteronyssinus mite culture extract is essentially fractionated by acetone and ammonium sulphate precipitations followed by anion-exchange high performance liquid chromatography. A high yield of a very pure Der pI allergen is obtained during the first isocratic run, as shown by sodium dodecylsulphate polyacrylamide gel electrophoresis, capillary electrophoresis, chromatofocusing and a two site monoclonal antibody enzyme-linked immunosorbent assay. Microsequencing revealed that the 25-residue sequence obtained is entirely in agreement with the sequence derived from the cDNA of Der pI. PMID- 1618984 TI - High-performance liquid chromatographic separation of detritylated oligonucleotides on highly cross-linked poly-(styrene-divinylbenzene) particles. AB - Detritylated oligonucleotides were separated by reversed-phase high-performance liquid chromatography on highly cross-linked polystyrene-based particles having a mean particle diameter of 2.3 microns. The addition of poly(vinyl alcohol) during polymerization, which resulted in the presence of hydroxyl groups on the surface of the poly(styrene-divinylbenzene) beads, was necessary to obtain baseline resolution of phosphorylated oligodeoxyadenylic acids with a chain length of up to 30 bases. The impact of temperature was investigated and optimum resolution was achieved at 40 degrees C. At pH 7.0, the retention times of oligonucleotides were found to depend on the ratio of bases and to increase in the order of C less than G less than A less than T. Under the same conditions, it was possible to separate phosphorylated from dephosphorylated oligonucleotides, the former being eluted earlier. Recoveries ranged from 92 to 100%. PMID- 1618985 TI - Application of capillary reversed-phase high-performance liquid chromatography to high-sensitivity protein sequence analysis. AB - A continuous gradient elution method for capillary column (less than 0.32 mm I.D.) liquid chromatography was developed. Gradient eluent from a microbore liquid chromatograph was split ahead of the injector so that an accurate percentage (2-3%) of the mobile phase delivered by the pump flowed through the capillary column. The outlet of the column was connected to a length of 0.075 mm I.D. fused-silica capillary tubing which, in turn, was connected to a 6-mm optical path length longitudinal capillary flow cell. Fused-silica capillary columns of 0.32 mm I.D. were slurry-packed efficiently with 7-microns spherical, 300 A pore size, C8 bonded-phase particles, and evaluated in terms of their ability to resolve mixtures of proteins, peptides or phenylthiohydantoin (PTH) amino acid derivatives. The gradient elution profiles agreed with those obtained using microbore (less than 2.1 mm I.D.) and larger bore columns. The minimum detectable amounts for proteins and PTH-amino acids on 0.32 mm I.D. capillary columns were 50 pg and 25 fmol, respectively. At a flow-rate of 3.6 microliters/min, proteins and peptides were recovered from the capillary columns in volumes of about 2-8 microliters. The use of a multiple-wavelength, forward optics detector for identifying tryptophan- and tyrosine-containing peptides is discussed. PMID- 1618986 TI - Selective high-performance liquid chromatographic purification of bispecific monoclonal antibodies. AB - The recent development of improved production techniques for bispecific monoclonal antibodies (biMAbs) has significantly increased interest in specific purification procedures. In this investigation, a general high-performance liquid chromatographic (HPLC) purification method is proposed that allows highly purified biMAbs to be obtained from mouse ascites fluid containing a mixture of different antibodies, i.e., parental MAbs, active biMAb and a mixture of randomly assembled heavy and light chains. Proteins from ascites fluid were precipitated with ammonium sulphate and applied to a high-performance protein A column to separate the total immunoglobulin fraction. BiMAbs were isolated from other immunoglobulins by two subsequent passages through a high-performance hydroxyapatite (HPHT) column. This purification protocol combines specificity of protein A for immunoglobulin G (IgG) and high selectivity of hydroxyapatite for different IgG idiotypes. All purification steps were performed rapidly and reliably by HPLC. This method was applied to the purification of six different biMAbs with consistently high yields, purity and homogeneity. This general purification method may prove extremely valuable when highly pure preparation of biMAbs is required, as for in vivo use. PMID- 1618987 TI - Characterization of the heterogeneity of polyethylene glycol-modified superoxide dismutase by chromatographic and electrophoretic techniques. AB - Covalent attachment of polyethylene glycol (PEG) chains to the enzyme Cu,Zn superoxide dismutase (SOD) produces a heterogeneous mixture of modified protein species. The heterogeneity of the product (PEG-SOD) derives from a variable stoichiometric combination of PEG with individual SOD molecules in addition to the polydispersity of the PEG reagent. Characterization of PEG-SOD presents significant challenges due in part to this heterogeneity in addition to the hybrid nature of the modified enzyme. The application of classical methods of protein characterization is not always successful for these PEG-proteins requiring the development of alternative or modified procedures. A series of chromatographic techniques including reversed-phase, ion-exchange, size exclusion, and hydrophobic interaction high-performance liquid chromatography along with electrophoretic techniques including isoelectric focusing, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and capillary zone electrophoresis have been developed for assessing the degree of heterogeneity of PEG-SOD samples which encompass a range of different stoichiometries. Examples will be given demonstrating the application of these techniques to characterize PEG-SOD samples of different composition produced during the course of the reaction between SOD and an activated PEG reagent. PMID- 1618988 TI - Peptide maps of five human pepsin isoenzymes and other aspartic proteinases. AB - Peptide maps of five individual human pepsins were developed using reversed-phase high-performance liquid chromatography after protein digestion with either Staphylococcus aureus proteinase (V8) or alpha-chymotrypsin. Human pepsins 3a, 3b and 3c produced almost identical peptide maps suggestive of proteins with very similar amino acid sequences. The map for human pepsin 1 was similar to pepsin 3b (the most predominant human pepsin) but less than half the expected amount of each equivalent peptide fragment was generated, indicating that the actual mass of digested protein used was less than the dry weight measurement would suggest, probably as a result of carbohydrate attached to pepsin 1. Comparison of human pepsin 3b maps with other aspartic proteinases confirmed a significant homology with swine pepsin A but not with endothiapepsin. The alpha-chymotrypsin digests compared with V8 gave more complex peptide maps as a result of its broader bond cleavage specificities. PMID- 1618989 TI - Influence of operating parameters on the preparative gradient elution chromatography of insulins. AB - The mass-overloaded separation of bovine and porcine insulins has been studied in the reversed-phase gradient elution mode. Strong solute-solute displacement effects have been found, which are related to the efficiency of the column used. Low flow-rates and small particle diameters maximise the displacements, as well as improve the resolution between the parent insulin and its desamido contaminant. The gradient slope did not substantially affect the separation between the parent insulins, but, due to the relative "S" values of the solutes, an increase in gradient slope improved the separation of the parent insulin from its desamido compound. An optimum pore size of 150 A was found for the insulins. Experiments to optimise the loadability were not carried out, but a recovery of 90% at a purity of 99.5% was obtained with a loading of 12 mg/g of porcine insulin. PMID- 1618990 TI - Chromatographic analysis of low-molecular-mass copper-binding ligands from the crab species Scylla serrata and Portunus pelagicus. AB - Two copper-binding proteins and a zinc-binding ligand were isolated from the hepatopancreas of the crab Portunus pelagicus. The copper-binding proteins behave similarly to those from the crabs Carcinus maenas and Scylla serrata, and were shown to be metallothioneins. Reversed-phase high-performance liquid chromatographic (HPLC) analysis confirmed the relative purity of both proteins with only cross-contamination between the two different forms of metallothioneins, and offers a good method to separate the two forms of metallothioneins. The vast difference in the retention times (and hence the hydrophobicity) in reversed-phase HPLC indicates that the two proteins could be conformationally very different. PMID- 1618991 TI - Prediction of peptide retention time in reversed-phase high-performance liquid chromatography. AB - Peptide retention in reversed-phase chromatography depends mainly on the amino acid composition of peptides and can therefore be predicted by summing the relative hydrophobic contributions of each constitutive amino acid residue. The prediction is correct for small peptides but overestimates the retention times of peptides larger than 10-15 residues. A new prediction model is proposed in which the contribution to peptide retention of each amino acid residue is not a constant but a decreasing function of peptide length. From the retention times of 104 peptides, the parameters of decreasing functions were estimated by a non linear multiple regression analysis. The contribution to peptide retention of charged, polar and non-polar residues appears to be differently affected by peptide length. The secondary structure of most peptides during reversed-phase high-performance liquid chromatography could be responsible for this. The high correlation between the predicted and observed retention times of peptides which were not used to establish the model indicates a good predictive accuracy of the new model. PMID- 1618992 TI - Influence of different N- and O-linked carbohydrates on the retention times of synthetic peptides in reversed-phase high-performance liquid chromatography. AB - Glycopeptides consisting of 6-19 amino acid residues and different mono- and disaccharides attached to single asparagine and serine residues were synthesized on solid-phase and were characterized by reversed-phase high-performance liquid chromatography and circular dichroism. It was shown that the decreased retention times due to glycosylation could be correlated with the increasing length of the sugar moiety. Phosphorylation of the same sequences reduced the retention times 1.6 times more than glycosylation with monosaccharides did. The binding to the column was dependent on the structure of the disaccharide when derivatized and glycosylated asparagine, the building block of N-glycopeptide syntheses was studied. However, this structural dependence of the elution times disappeared in the final glycopeptides. Although both glycosylation and phosphorylation resulted in altered secondary structure of the peptide backbone, it appears that the retention times reflect the increased hydrophilicity more strongly than induced conformational orientation on the surface of the bonded phase. PMID- 1618993 TI - Chromatographic analysis of tropomyosins from rabbit skeletal, chicken gizzard and earthworm muscle. AB - Tropomyosins from rabbit skeletal, chicken gizzard and earthworm muscle all exist as dimeric, ca. 100% alpha-helical coiled-coil species in benign media. Two major tropomyosin isoforms from each muscle source have been identified and can be conveniently designated alpha (fast) and beta (slow) based on electrophoretic mobility under denaturing conditions. The ratio of alpha to beta chains is ca. 3 4:1 for rabbit skeletal and ca. 1:1 for chicken gizzard and earthworm tropomyosins. Each chain from the former two muscle sources has been sequenced, thus providing a molecular basis for interpreting the in vivo population of homo- and hetero-dimers. The characteristics of each purified tropomyosin in weak-anion exchange, strong-cation exchange and reversed-phase high-performance liquid chromatography are described. Binding to and/or elution from the reversed-phase matrix results in dissociation into highly helical monomeric chains. This mode of chromatography separates the alpha and beta chains of earthworm and chicken gizzard tropomyosins, but not those of the rabbit protein. Both anion- and cation exchange chromatography use mild (benign) elution conditions under which the native, in vivo dimer population should be preserved. Only the rabbit protein exhibited peak separation on the anion-exchange resin, with peak assignment corresponding to the known molecular organization of homo- and hetero-dimers. In strong cation-exchange analysis, all three tropomyosins exhibit a chromatographic transition near pH 6.5, possibly the result of histidine(s) titration. Collectively, the chromatographic data confirm the present understanding of the in vivo mixture of dimers for tropomyosin from rabbit skeletal and chicken gizzard. It is concluded that native earthworm tropomyosin exists predominantly as an alpha beta hetero-dimer. PMID- 1618994 TI - Clinical review 35: Growth factors and their potential clinical value. PMID- 1618995 TI - Androstenedione metabolism in cultured human osteoblast-like cells. AB - Bone is a target organ of androgens. The mechanism by which these steroids exert their action within bone cells is still poorly understood. The metabolism of androstenedione, the major circulating androgen in women, was, therefore, assessed in osteoblast-like bone cells cultured from bone of 16 postmenopausal women (mean age, 69 yr; range, 56-80) and 3 elderly men (mean age, 71 yr; range, 69-73) undergoing total hip replacement. Each cell strain was incubated under standardized conditions with varying concentrations of [1,2,6,7 3H]androstenedione (0.05-5 microM). In every instance 5 alpha-reduced metabolites and 17 beta-hydroxysteroids were formed. There was no correlation between the volumetric density of the resected bone and androstenedione metabolism of the corresponding cultured bone cell strains. The apparent Km for the 5 alpha reductase activity (sum of androstanedione and dihydrotestosterone) of all 19 cell strains was 0.7 +/- 0.1 microM (mean +/- SEM), and the apparent Km for 17 beta-hydroxysteroid dehydrogenase (sum of testosterone and dihydrotestosterone) was 2.3 +/- 0.8 microM (mean +/- SEM), values similar to those reported for other androgen target organs. Our results demonstrate that human osteoblast-like cells have the capacity to transform androstenedione into the more potent biological androgens testosterone and dihydrotestosterone. Since the Km values of both 5 alpha-reductase and 17 beta-hydroxysteroid dehydrogenase exceed the serum androstenedione concentration, the formation of testosterone and dihydrotestosterone appears to be mainly a function of substrate availability. PMID- 1618997 TI - Sex steroid priming effects on growth hormone response to pyridostigmine throughout the menstrual cycle. AB - To explore the effect of estradiol and progesterone on the GH response to the indirect cholinergic agonist pyridostigmine nine healthy women were challenged with both active drug and placebo at three time points in two consecutive menstrual cycles: a total of six neuroendocrine tests. A randomized, double blind, counterbalanced design was used. Subjects were tested in the early follicular, mid-cycle, and luteal phases of the cycle. A cannula was inserted in a forearm vein after an overnight fast and baseline GH, estradiol, and progesterone samples were drawn. After 120 mg oral pyridostigmine or placebo tablets further blood samples for GH analysis were drawn at intervals over 3 h. When expressed as maximum change from baseline (delta GH) mean GH responses to pyridostigmine increased incrementally from early (8.4 +/- 2.7 micrograms/L) through mid (18 +/- 1.3 micrograms/L) to late (22.2 +/- 1.9 micrograms/L) cycle. This represents a significant effect of cycle phase on the GH response to pyridostigmine (P less than 0.001, as assessed by analysis of variance). Responses to placebo did not vary. Plasma estradiol values were significantly correlated with GH responsivity to active drug throughout the cycle (P less than 0.02). Multiple regression analysis also revealed a significant positive correlation between progesterone levels and GH response to pyridostigmine (P less than 0.02). Estrogens augment GH responses to other challenges but a priming effect of progesterone on GH responsivity has not previously been demonstrated. Various mechanisms are discussed including a possible sex steroid priming effect on acetylcholine neurotransmission. PMID- 1618996 TI - Decreased hypoglycemic effect of insulin at night in insulin-dependent diabetes mellitus and healthy subjects. AB - Diurnal variations in insulin-induced hypoglycemia and in plasma counterregulatory hormone concentrations were explored in eight insulin-dependent diabetic and six healthy subjects during a 100-min iv insulin infusion performed at 0300 h and 1500 h. In healthy subjects, plasma glucose concentrations (mean +/ SD) fell by 35 +/- 2% during the daytime test and by 26.5 +/- 2% during the nocturnal test (P less than 0.01). Plasma cortisol, GH, and epinephrine concentrations increased more during the daytime than during the nocturnal test. In contrast, plasma glucagon concentrations rose more during the nocturnal tests. In insulin-dependent diabetes mellitus patients, insulin infusion had to be interrupted in three subjects because plasma glucose fell below 1.9 mmol/L 80 min after the beginning of the test. In the other five patients plasma glucose fell by 34 +/- 5% during the daytime test while no significant decrease in plasma glucose was observed in any of the eight patients during the nighttime test. Counterregulatory hormone concentrations were consistent with the results of plasma glucose, with no change during the nocturnal test and significant increases in cortisol, GH, and epinephrine during the daytime test. These results show that insulin sensitivity is decreased at night in comparison to midafternoon in healthy subjects and that in insulin-dependent diabetes mellitus patients this phenomenon is exaggerated, even in patients with defective counterregulation to hypoglycemia. PMID- 1618998 TI - Measurement of derivatives of proinsulin-like growth factor-II in serum by a radioimmunoassay directed against the E-domain in normal subjects and patients with nonislet cell tumor hypoglycemia. AB - We describe a modified RIA using a rabbit polyclonal antiserum directed against the first 21 amino acids of the E-domain (E-21) of proinsulin-like growth factor II (pro-IGF-II). For standardization, we purified big IGF-II from patients with nonislet cell tumor hypoglycemia (NICTH). Under the conditions of our assay there was no significant interference from IGF-binding proteins. The big IGF-II present in the serum of a patient with NICTH displaced [125I]E-(1-21) from antibody parallel to our big IGF-II standard. We found a progressive rise in E-21 immunoactivity (IA) during childhood, with somewhat higher values in girls than in boys. In normal adults the mean E-21 IA level was 138 +/- 49 (+/- SD) micrograms/L. Women with twin pregnancies had higher E-21 IA than women with single pregnancies (302 +/- 66 compared with 120 +/- 18 micrograms/L). We found a marked elevation of E-21 IA in patients with NICTH due to sarcomas (n = 3), hepatoma (n = 2), adrenal carcinoma (n = 1), and carcinoma of the lung (n = 1). No elevation of E-21 IA was present in the serum of a hypoglycemic patient with a hypernephroma or another patient with carcinoma of the lung. Marked elevation of E-21 IA was observed in the serum of patients with renal failure receiving chronic hemodialysis. We conclude that this assay will prove useful in the diagnosis of NICTH in patients who are not azotemic and the investigation of the role of the kidney in clearing products of pro-IGF-II processing. PMID- 1618999 TI - Effects of thyroid hormone on sex hormone-binding globulin gene expression in human cells. AB - We have used a human hepatoblastoma cell line to establish a model system for thyroid hormone (T3) action in human cells. HepG2 cells were grown for 3 days in Dulbecco's Modified Eagle's Medium containing fetal calf serum and were maintained in serum-free medium for experimental manipulations. [125I]T3 incubated with cells was bound by newly secreted protein and degraded. After 24-h exposure to HepG2 cells in Dulbecco's Modified Eagle's Medium, only 35-40% of the radioactivity was recovered as authentic T3. Degradation of hormone was neither time nor concentration dependent, and occurred to a greater degree in the absence of cells, suggesting an interaction between the hormone and the plastic culture dish. After 4 days, in the absence of fetal calf serum and considering hormone binding and degradation, the concentration of free T3 available to cells was approximately 15% of that added initially. Sex hormone-binding globulin (SHBG) was secreted by HepG2 cells in the absence of T3 and was specifically stimulated by the addition of T3. After 4 days, maximum stimulation occurred with added T3 concentrations of 10(-8) M or greater, and half-maximal stimulation of SHBG secretion was observed at about 3 x 10(-11) M free T3. No significant changes in total secreted protein or cellular DNA content were observed under similar conditions. Northern analysis of RNA extracted from HepG2 cells revealed a SHBG mRNA of 2 kilobases, which was stimulated in a dose-responsive manner by T3. No stimulation of corticosteroid-binding globulin mRNA was seen. Stimulation of the SHBG gene in HepG2 cells may be a useful model for investigation of T3 action in human cells. PMID- 1619000 TI - Circadian rhythm abnormalities in totally blind people: incidence and clinical significance. AB - When people are completely isolated from environmental time cues, their circadian rhythms free run with a nearly 24-h cycle, generated by an internal body clock. Free-running temperature, cortisol, and melatonin rhythms have also been described in totally blind people, even though they were living in normal society and had access to abundant time cues; thus an intact visual system may be essential for synchronization of the circadian system. However, because of the small numbers of subjects studied, the incidence and clinical significance of circadian rhythm abnormalities among the blind has remained uncertain. In this study, plasma melatonin (n = 20), cortisol (n = 4), and sleep propensity (n = 1) were measured in serial samples taken from totally blind subjects for 24 h. Most totally blind subjects had circadian rhythm abnormalities. In about half of the subjects, the rhythms were free-running. Some blind subjects suffered recurrent insomnia and daytime sleepiness that were maximal when the internal rhythms were out of phase with the preferred sleep times. The high incidence of abnormal circadian rhythms in blind people underscores the importance of the light-dark cycle as an important environmental synchronizer for the human circadian system. PMID- 1619001 TI - Genetic variation of human sex hormone-binding globulin: evidence for a worldwide bi-allelic gene. AB - Genetic variation of human sex hormone-binding globulin (SHBG) has been investigated on 1690 unrelated neuraminidase-treated serum samples using isoelectric focusing followed by transfer to nitrocellulose membranes and immunostaining. Three clearly distinct isoelectric focusing patterns, consistent with the expression of an autosomal genetic system, were identified. Using allele frequencies, calculated on the basis of a bi-allelic gene, an excellent agreement between observed and expected phenotype numbers was obtained in every examined population sample. Family data along with the observed distribution of the three SHBG phenotypes among racially different groups and sexes indicate that SHBG is worldwide encoded by two autosomal codominant alleles. Compared with healthy Belgian blood donors no statistically significant differences were noted for the allele frequencies among 399 patients and 70 hirsute women of Belgian origin. Evidence is also presented that the subunit produced by the variant allele (SHBG2) has a higher molecular mass than the one produced by the regular allele (SHBG1) and that the three SHBG genotypes have identical binding characteristics for 5 alpha-dihydrotestosterone. PMID- 1619002 TI - Effects of triiodothyronine (T3) and identification of specific nuclear T3 binding sites in cultured human fetal epiphyseal chondrocytes. AB - The effects of T3 on cultured human fetal epiphyseal chondrocytes were assessed by studying its effects on DNA synthesis and alkaline phosphatase activity. DNA synthesis was evaluated as follows: after 48-h incubation in Ham's F-12 serum free medium, cultured chondrocytes were incubated with or without T3 (0.1-100 nM) in MCDB-104 serum-free medium for different periods of time (2-10 days), with the addition of [3H]thymidine (5 microCi/mL) for the last 24 h. Confluent cultured chondrocytes in 25-cm2 tissue culture flasks were incubated in Ham's F-12 serum free medium for up to 9 days with or without T3 (0.1-100 nM); the cellular cytoplasmic fraction was obtained, and alkaline phosphatase activity was evaluated using paranitrophenylphosphate as a substrate. No significant effects of T3 (0.1-100 nM) on DNA-[3H]thymidine incorporation were observed in any experiment (n = 17) for any gestational age (12-39 weeks) or for any incubation period studied (2-10 days). However, a significant (P less than 0.025 or more) stimulatory effect of T3 (0.1-100 nM) on alkaline phosphatase activity was observed after 9 days of incubation. This effect was highest for 5 nM T3 and was present in cultured chondrocytes from human fetuses of all ages studied (13-40 weeks). Cultured human fetal epiphyseal chondrocytes from human fetuses 12-40 weeks old (n = 8) showed specific nuclear binding sites for T3. The binding capacity was 27.14 +/- 2.84 fmol/100 micrograms DNA, and the Kd was 0.66 +/- 0.14 x 0.1 nM (mean +/- SEM), with no significant differences among fetal ages. In conclusion, our results show that T3 elicits a biological response in cultured human fetal epiphyseal chondrocytes and has specific nuclear binding sites. Since alkaline phosphatase is closely related to the mineralization of epiphyseal cartilage, these results suggest that thyroid hormones could regulate this process. PMID- 1619003 TI - Intact parathyroid hormone overestimates the presence and severity of parathyroid mediated osseous abnormalities in uremia. AB - To examine the possibility that uremia alters the relationship between bioactive PTH serum concentrations and its osseous end-organ response, we evaluated the relationship between circulating intact PTH and bone turnover in 39 end-stage renal disease patients with hyperparathyroid-mediated bone disease of varying severity. We excluded from analysis patients with coexistent defects in mineralization to insure that bone remodeling indices primarily reflected the effects of PTH. The distribution of serum PTH levels ranged from normal to markedly elevated. Regression analysis between circulating intact PTH concentrations, measured by a two-site immunoradiometric assay, and osseous indices of hyperparathyroidism, determined by quantitative bone histological analysis of iliac crest bone biopsies, showed that bioactive serum PTH levels correlated linearly with bone formation (r = 0.836), woven osteoid volume (r = 0.718), and marrow fibrosis (r = 0.856), and nonlinearly with parameters of bone resorption (r = 0.760). From these functional relationships, we found that the average serum intact PTH level of approximately 165 pg/mL, a value that exceeds the upper limit of intact PTH in nonuremic subjects (65 pg/mL) by 2.5-fold, defines the upper normal limit of bone turnover in uremic subjects. Indeed, the average serum PTH concentrations reached 500 pg/mL before histological evidence of severe hyperparathyroidism developed in uremic subjects. These findings demonstrate that elevated PTH concentrations are necessary to maintain normal bone remodeling in the uremic setting. Consequently, it may not be necessary to attain normal serum intact PTH levels to control the osseous manifestations of PTH excess in uremic subjects. PMID- 1619004 TI - Effects of systemic growth hormone (GH) administration on regional adipose tissue in children with non-GH-deficient short stature. AB - Chronic administration of exogenous GH to GH-deficient children is associated with a selective depletion of the abdominal sc fat depot and a resultant relative increase in gluteal, relative to abdominal, adipocyte lipid content. In GH deficient children, the degree of this change in relative lipid content per adipocyte appears to be correlated with decreases in sensitivity of abdominal subcutaneous fat to the antilipolytic action of insulin. We studied abdominal and gluteal sc adipose tissue from 10 children with short stature (height less than 5% ile, growth velocity less than 5 cm/yr, bone age delayed at least 2 yr), who were not GH deficient based upon provocative testing (non-GH-deficient short stature) 1) before beginning and 2) after 3 months of therapy with exogenous GH (Humatrope, 0.1 mg/kg sc 3 times/week). In abdominal and gluteal adipocytes, we measured lipid content, rates of reesterification of fatty acids released by ongoing lipolysis and rates of in vitro lipolysis and lipogenesis in response to insulin, adenosine, and various adrenoreceptor agonists. These biochemical measures were correlated with measures of statural growth and adipose tissue distribution in each subject. We found that GH therapy was associated with a significant reduction in abdominal adipocyte size (0.48 microgram +/- 0.08 lipid per cell prior to therapy vs. 0.43 microgram +/- 0.08 lipid per cell after therapy, P less than 0.05) and a significant increase in responsiveness of gluteal sc adipose tissue to the lipogenic actions of insulin. The significant correlations of changes in abdominal adipocyte volume with changes in regional adipose tissue insulin sensitivity that were noted in GH-deficient children were not noted in this subject population, perhaps due to effects of endogenous GH on pretreatment insulin responsiveness of adipose tissue. These data reaffirm that GH has site-specific effects on regional adipose tissue depots. PMID- 1619005 TI - Effect of low and high intensity exercise on circulating growth hormone in men. AB - We hypothesized that circulating GH would increase only if a threshold of work intensity [corresponding to the anaerobic or lactate threshold (LT)] was exceeded. Ten healthy male volunteers (18-35 yr) first performed ramp-type progressive cycle-ergometer exercise to determine the LT and the maximal oxygen uptake. On subsequent mornings after an overnight fast, each subject performed bouts of 1, 5, and 10 min constant work rate exercise of either high intensity (above LT) or low intensity (below LT). A 1-h interval separated exercise bouts. Gas exchange (breath-by-breath), GH, immunoreactive insulin, glucose, lactate, pyruvate, and epinephrine and norepinephrine were measured at regular intervals. After the 10-min bouts of high compared with low intensity exercise, lactate was 7.2 +/- 3.7 mmol/L vs. 1.4 +/- 1.3, P less than 0.05; epinephrine was 1,113 +/- 519 pmol/L vs. 496 +/- 273, P less than 0.05; and norepinephrine was 7.89 +/- 3.45 nmole/L vs. 2.83 +/- 1.34, P less than 0.05. GH did not increase significantly from preexercise baseline during low intensity exercise (e.g., GH after 10-min low intensity exercise changed from baseline values by 1.5 +/- 2.0 micrograms/L, NS). Although lactate was elevated after 5-min of high intensity exercise, peak GH was significantly elevated (mean increase above baseline of 7.7 +/- 2.4 micrograms/L, P less than 0.05) only after 10 min of high intensity exercise (increases in 9 of 10 subjects). The GH increase occurred despite simultaneous increases in both IRI and glucose. A minimum duration of 10 min, high intensity exercise consistently increased circulating GH in adult males. PMID- 1619006 TI - A randomized comparison of intranasal and injectable octreotide administration in patients with acromegaly. AB - Fifteen acromegalic patients received four single doses of octreotide in random order (500 micrograms, 1000 micrograms, and 2000 micrograms applied intranasally and 100 micrograms given sc). Serum octreotide and GH data were subjected to pharmacokinetic analyses, and local nasal effects were evaluated by acoustic rhinometry. Average areas (+/- SEM) under the serum octreotide curves were: 2000 micrograms: 4597 +/- 536; 1000 micrograms: 1923 +/- 439; 500 micrograms: 957 +/- 168; and 100 micrograms sc: 896 +/- 81 micrograms.L-1.min (n = 13). The calculated relative availability was 27% +/- 0.03; 22% +/- 0.05; 22% +/- 0.03, respectively, for the three nasal doses. The rate of absorption after intranasally administered octreotide was greater than after sc application: t1/2 ka: 7.1 +/- 1.6; 7.9 +/- 1.6; 11.3 +/- 1.9, respectively, vs. 24.1 +/- 2.5 min, whereas the rates of disappearance were similar. GH suppression started immediately after application and reached minimum levels 1-2 h later. The average intervals during which serum GH was below 50% of preadministration values were: 2000 micrograms: 544 +/- 47; 1000 micrograms: 423 +/- 56; 500 micrograms: 289 +/- 52 vs. 351 +/- 34 min after sc injection of 100 micrograms. With 2000 micrograms intranasally all but one of the 15 patients attained constant suppression of serum GH below 5 micrograms/L for 273 to 680 min. Pharmacokinetic analysis demonstrated that 100 micrograms sc and 1000 micrograms intranasally induced the same GH suppressive effect and that 2000 micrograms intranasally approximately doubled the duration of action. Acoustic rhinometry was performed after nasal application of the largest dose of 2000 micrograms and after carrier (n = 9). A highly significant tumescence of the nasal mucosa was maximal after 10 min and gradually receded over the next 2 h. However, this was felt by the patients to be acceptable. The effect was caused by octreotide per se and was probably due to vasodilation. PMID- 1619007 TI - Effect of body mass index and fat distribution on insulin sensitivity, secretion, and clearance in nonobese healthy men. AB - The effects of variation in body mass index (BMI; kg/m2) and body fat topography on insulin sensitivity, secretion, and clearance were determined in a group of 146 nonobese nondiabetic males. Volunteers underwent an i.v. glucose tolerance test, with determination of plasma glucose, insulin, and C-peptide levels. BMI was taken as a measure of overall adiposity, while skinfold thickness ratios were used to assess the centrality of fat distribution and the localization of central fat within the trunk. Measurements of insulin sensitivity, secretion, and clearance were obtained by mathematical modelling of the i.v. glucose tolerance test concentration profiles. Increasing BMI and centrality of fat distribution had no significant effect on glucose tolerance, but were independently associated with diminished insulin sensitivity and increased insulin secretion. The elevation in secretion occurred almost entirely during the second phase of pancreatic insulin release. These results show that the variations in insulin sensitivity and secretion that have often been reported in obesity are also present in a group within the normal range of BMI. However, the absence of any decrease in hepatic uptake, also reported in the obese, indicates that this might be an additional mechanism recruited to maintain glycemic control at higher levels of adiposity. Localization of central fat in the lower trunk was correlated with elevated first phase insulin secretion, but no concomitant change in insulin sensitivity. There may, therefore, be a direct effect of the distribution of central fat on insulin secretion. PMID- 1619008 TI - Growth hormone and insulin-like growth factor-I stimulate hormonal function and proliferation of thymic epithelial cells. AB - We have investigated the role of GH and insulin-like growth factor-I (IGF-I) in controlling the secretion of thymulin, a hormone produced by thymic epithelial cells (TEC). Thymulin plasma concentrations (mean +/- SD) were increased in 21 patients with acromegaly compared to those in 30 controls, as assessed by bioassay (4.24 +/- 0.97 vs. 2.67 +/- 0.87; P less than 0.001) and RIA (561 +/- 241 vs. 315 +/- 113 pg/L; P less than 0.01). Good correlations were observed between plasma levels of thymulin and IGF-I (P less than 0.001). In vitro experiments demonstrated that both recombinant human GH and IGF-I significantly increased thymulin production in culture supernatants of normal human TEC and a rat TEC line. In parallel, IGF-I also significantly stimulated the proliferation of human TEC, as measured by bromodeoxyuridine incorporation. Additionally, the stimulatory effect of GH on thymulin production was abrogated by both an anti-IGF I antibody and an anti-IGF-I receptor antibody. These results support a role for GH and IGF-I in the control of thymic hormonal function in man and suggest that the effect of GH may be mediated by local secretion of IGF-I within the thymus. PMID- 1619009 TI - A radioimmunoassay for measurement of 3,5,3'-triiodothyronine sulfate: studies in thyroidal and nonthyroidal diseases, pregnancy, and neonatal life. AB - A highly sensitive, specific, and reproducible RIA has been developed to measure T3 sulfate (T3S). Only T4 sulfate cross-reacted significantly (approximately 3%) in the RIA; rT3 sulfate, T4, T3, rT3, and diiodothyronine cross-reacted less than 0.01%. T3S was bound by thyronine-binding globulin and albumin in serum. The free fraction of T3S in four normal sera averaged 0.25% compared to a value of 0.35% for T3. Therefore, T3S was measured in ethanol extracts of serum. Recovery of the nonradioactive T3S added to serum averaged 92%. The dose-response curves of inhibition of binding of [125I]T3S to anti-T3S antibody by serial dilutions of serum extracts were essentially parallel to the standard curve. The detection threshold of the RIA was 20 pmol/L (1.5 ng/dL). The coefficient of variation averaged 7.8% within an assay and 11% between assays. The serum concentration of T3S was (mean +/- SE) 76 +/- 7.2 pmol/L in normal subjects, 268 +/- 29 in hyperthyroid patients with Graves' disease, 92 +/- 28 in hypothyroid patients, 201 +/- 32 in patients with systemic nonthyroidal illnesses, 40 +/- 6.2 in pregnant women (15-31 weeks gestation), and 429 +/- 39 in cord sera of newborns; the values in hyperthyroidism, nonthyroidal illnesses, and newborns were significantly different from normal (P less than 0.01). The mean concentration of T3S in amniotic fluid samples at 15-31 weeks gestation (90 +/- 1.3 pmol/L) was significantly higher than the corresponding value in maternal serum (P less than 0.05) and significantly lower than the corresponding value in newborn cord blood serum (P less than 0.001). Oral administration of sodium ipodate (Oragrafin; 3 g) to two hyperthyroid patients was associated with a 76-190% increase in serum T3S at 8 h, followed by a gradual decrease to a nadir that was 25-60% of the baseline value 2-3 days after ipodate ingestion. We conclude that 1) T3S is a normal component of human serum, and its levels change substantially in several physiological and pathological conditions; 2) sulfation pathway plays an important role in the metabolism of iodothyronines in man; and 3) high serum T3S levels in newborns and low normal levels in pregnancy despite elevated thyronine binding globulin levels may signify markedly different metabolism of T3S in the mother and fetus. PMID- 1619010 TI - Measurement of estradiol-17-fatty acid esters in human tissues. AB - We have developed a gas chromatographic/mass spectral method for the sensitive and reproducible measurement of estradiol-17-fatty acid esters in human tissues and blood. To provide an internal standard for quantification, a trideuterated analog of a representative estradiol ester is added to the tissues. Estradiol (E2) released from the nonpolar ester fraction by alkaline hydrolysis is derivatized to form the ditrimethylsilyl ether and then analyzed by gas chromatographic/mass spectral, monitoring the molecular ions mass per U charge of the ditrimethylsilyl derivative of E2 and [2H3]E2. There are low but detectable levels of E2 ester in the blood of cycling females; there are none in urine. While the E2 ester is present in breast cyst fluid, its concentration, 77-140 pmol/L, is considerably less than E2, 110-2,863 pmol/L. But there is a large amount of E2 ester in fat. In premenopausal women the average E2 ester in fat (sc and omental) is 957 +/- 283 38 fmol/g (SEM); in women who are menopausal less than 12 yr, the E2 ester in fat is 669 +/- 158 fmol/g; in women who are menopausal at least 15 yr, the fat level is 399 +/- 146 fmol/g. Muscle from the same women have lower concentrations of the ester; in 8 out of 12 muscle specimens it was not detectable. The E2 esters are extremely potent estrogens. Although they are hormonally active they require enzymatic hydrolysis to exert their hormonal action. These studies show that these long chain esters of E2 are sequestered in fatty tissues, wherein they represent a protected store of preformed hormone. Under the proper stimulation, adipose tissue can activate the estrogenic signal through the action of hormonally sensitive esterases. Thus, through signaling between estrogen sensitive tissues and neighboring fat cells, a local paracrine loop may exist. PMID- 1619012 TI - A point mutation in the 3,5,3'-triiodothyronine-binding domain of thyroid hormone receptor-beta associated with a family with generalized resistance to thyroid hormone. AB - A tight linkage between generalized resistance to thyroid hormone (GRTH) and the thyroid hormone receptor-beta (TR beta) gene is indicated. We evaluated a family with GRTH for the TR beta gene. We found that a new point mutation, consisting of a cytosine to adenine replacement at nucleotide position 1642, resulted in substitution in codon 448 in the T3-binding domain of TR beta. This base substitution was found in only one allele of affected members, but not in unaffected members of the family. The in vitro translation products of this mutant TR beta gene demonstrated significantly reduced T3-binding affinity. Previously, others have reported a kindred with GRTH, in that the same codon was subjected to proline to histidine replacement due to a mutation consisting of a cytosine to adenine replacement at nucleotide position 1643. There appeared to be a significant phenotypic difference between our kindred and that described by others. PMID- 1619011 TI - Thyrotoxicosis after needle aspiration of thyroid cyst. AB - We report a new type of thyrotoxicosis (postaspiration thyrotoxicosis) that occurred after needle aspiration of thyroid cysts. In a retrospective study five patients with thyroid cysts developed transient thyrotoxicosis without significant symptoms of hyperthyroidism after needle aspiration. These patients had elevated serum thyroid hormone levels with suppressed serum TSH and thyroid radioiodine uptake. The thyroid hormone content in the cystic fluid was greater in patients who developed thyrotoxicosis than in patients who did not. In a prospective study we examined thyroid function tests after needle aspiration in 52 consecutive patients with thyroid cysts and 63 patients with solid thyroid nodules and confirmed an occurrence of postaspiration thyrotoxicosis in a patient with thyroid cyst. Our observation indicates that postaspiration thyrotoxicosis occurs only in patients with thyroid cyst and that the incidence of this disorder is probably less than 1% of patients who undergo thyroid needle aspiration. Although the exact mechanism of elevated serum hormone levels is unknown, an inflammatory process after needle aspiration might have triggered the release of thyroid hormone. PMID- 1619013 TI - Tyrosine kinase activity of skeletal muscle during insulin infusion in humans. AB - Insulin receptor tyrosine kinase is stimulated by insulin in vivo, and this provides a mechanism by which the signal from insulin is transmitted into target cells. This study examined the time course of the in vivo activation of the kinase. Five nondiabetic Pima Indians had a euglycemic clamp at an insulin dose of 600 mU/min.m2, resulting in plasma insulin concentrations of about 15 nM by 30 min. Percutaneous muscle biopsies were taken from the vastus lateralis before and at regular intervals during insulin infusion, and the in vivo and in vitro tyrosine kinase activities were measured. There was a rapid in vivo activation of the kinase, detectable at less than 10 min and reaching a maximum within 30 min of insulin infusion. The time course of in vivo kinase activity, plasma insulin concentrations, and insulin-mediated glucose disposal rates displayed parallel patterns, indicating close interrelationships among these variables. The insulin concentration at which the kinase activity was maximal was about 10 nM both in vivo and in vitro. In vitro, however, this maximum increased with the degree of the kinase activation in vivo, indicating that the kinase potential in vitro is dependent on previous insulin exposure in vivo. We conclude that in vivo activation of the insulin receptor tyrosine kinase in human skeletal muscle is a rapid process, related to insulin action on glucose disposal, and that circulating insulin primes inactive insulin receptor molecules for subsequent tyrosine kinase activation by a mechanism that remains to be elucidated. PMID- 1619014 TI - Postparathyroidectomy transient thyrotoxicosis. AB - Three patients are described who had spontaneously resolving transient thyrotoxicosis after resection of a parathyroid adenoma without thyroidectomy or an apparent thyroid abnormality before or during surgery. All had documented thyrotoxicosis that developed within 2 weeks after surgery, which was clinically symptomatic in two of three patients. The thyrotoxicosis was associated with subnormal radioactive iodine thyroid uptake when performed in the two symptomatic patients and was consistent with a postsurgical inflammatory etiology secondary to thyroid gland trauma during parathyroidectomy. In all patients, the clinical and biochemical evidence of thyrotoxicosis resolved within 2 months. Antithyroglobulin and antimicrosomal antibodies were not detected in the two patients who had a complete recovery 3 months after surgery. However, in the patient who had autoimmune thyroiditis, hyperthyroidism due to Graves' disease subsequently developed 19 months after parathyroidectomy and was associated with increasing titers of antithyroglobulin and antimicrosomal thyroidal autoantibodies. From these observations, we conclude that 1) spontaneously resolving transient thyrotoxicosis of varying severity may occur in some patients after parathyroidectomy, which could be secondary to intraoperative thyroid gland manipulation, and 2) while the occurrence of subsequent Graves' hyperthyroidism in a patient with underlying autoimmune thyroiditis may have been a coincidence, this observation also raises the possibility that thyroidal autoantigen released during parathyroidectomy may trigger the reactivation of autoimmune thyroid disease in a predisposed subject. PMID- 1619015 TI - Reversal of diet-induced catabolism by infusion of recombinant insulin-like growth factor-I in humans. AB - Treatment of catabolic conditions with insulin-like growth factor I (IGF-I), the peptide that mediates some of the anabolic growth-promoting effects of GH, offers potential advantages of avoiding the hyperglycemia caused by treatment with GH. A state of moderate catabolism was produced in six normal, young adult volunteers by restricting their daily dietary intake to 20 kilocalories/kg/day. During the last 6 days of two 2-week diet-study periods, they received either IGF-I (12 micrograms/kg/h by i.v. infusion over 16 h) or GH (0.05 mg/kg/day by sc injection). IGF-I improved nitrogen balance from -236 +/- 45 mmol/day (+/- SE) during diet alone, to -65 +/- 40 mmol/day (P less than 0.001) during the last 4 days of IGF-I infusion. A similar effect was produced by GH. IGF-I infusion decreased fasting blood glucose from 4.94 +/- 0.91 mmol/L to 3.13 +/- 0.44 mmol/L (P less than 0.001), while GH raised blood glucose values (4.75 +/- 1.01 mmol/L on diet alone, to 5.48 +/- 1.00 during the period of GH treatment; P less than 0.05). Despite these differences in blood glucose, IGF-I infusions decreased serum insulin (74.9 +/- 26.8 pmol/L on diet alone, to 16.7 +/- 1.5 pmol/L during IGF-I) and serum connecting-peptide concentrations (2.14 +/- 0.89 mmol/L on diet alone, to 0.97 +/- 0.14 during IGF-I), while GH raised insulin (109.4 +/- 31.3 pmol/L, P less than 0.05 during GH) and connecting-peptide (3.12 +/- 0.59 mmol/L, P less than 0.02). At the dose of each hormone used, the attenuation of nitrogen wasting produced by infusions of IGF-I was similar in magnitude and timing to that produced by injections of GH. The reduction in serum glucose concentrations produced by IGF-I compared with the increase in glucose noted during GH treatment, could benefit hyperglycemic catabolic patients. PMID- 1619016 TI - Sinus node function in hyperthyroid patients. AB - We have studied the electrophysiology of the sinus node and the role of the autonomic nervous system on sinus node function in 8 thyrotoxic patients of both sexes, 37.5 +/- 4.3 (mean +/- SE) yr old. The resting heart rate (RHR), the sino atrial conduction time (SACT), and the sinus node recovery time (SNRT) were measured in the untreated condition (basal), after sympathetic blockade with propranolol 0.2 mg/kg body weight (BW) i.v. infusion, and after complete autonomic blockade with the additional administration of atropine 0.04 mg/kg BW i.v. bolus. 1) In the thyrotoxic patients the RHR was higher [117 +/- 6 beats per min (bpm)] than in 20 normal subjects (73 +/- 1 bpm, P less than 0.001), whereas the SACT and SNRT values were not different. 2) After sympathetic blockade with propranolol, the RHR decrement and SACT increase were greater in the hyperthyroid patients than in normal subjects, whereas there was no difference in SNRT values between the two groups. 3) In the thyrotoxic patients the complete autonomic blockade reestablished the electrophysiological parameters to values similar to those observed in basal condition. In conclusion, in thyrotoxic patients the intrinsic activity of the sinus node is increased. It appears that this is a direct consequence of thyroid hormone excess, rather than an effect of extrinsic influences exerted by the autonomic nervous system on sinus node activity. PMID- 1619017 TI - Maternal side effects of prenatal dexamethasone therapy for fetal congenital adrenal hyperplasia. AB - Prenatal treatment of virilizing congenital adrenal hyperplasia in female fetuses via maternal dexamethasone (Dex) therapy (1-1.5 mg/day) from first trimester to birth was associated with excessive weight gain (47-56 pounds at 35-37 weeks gestation), Cushingoid facial features, severe striae resulting in permanent scarring, and hyperglycemic response (8-11.7 nmol/L) to oral glucose administration in all our experience (three cases). Other symptoms included hypertension, gastrointestinal intolerance, or extreme irritability. Previous pregnancies were uncomplicated by these problems. In each case, first or second trimester amniotic fluid 17-hydroxyprogesterone (17OHP, 17-41 nmol/L; normal less than 0.4 nmol/L), androstenedione (22-31 nmol/L, normal less than 5 nmol/L), and testosterone levels (0.54-0.7 nmol/L, normal less than 0.4 nmol/L) during Dex treatment were elevated regardless of the newborn genital outcome. Maternal serum estriol (E3) levels in one mother (normal newborn genitalia) were consistently low (less than 0.2 nmol/L) during the second and third trimester. In two mothers (partially virilized newborn genitalia) initial second trimester E3 levels were unsuppressed (11, 17.4 nmol/L) and suppressed (less than 1.4 nmol/L) following short-term increased dose. CONCLUSION: prenatal Dex treatment of virilizing congenital adrenal hyperplasia at a dose of 1-1.5 mg daily throughout gestation is associated with significant maternal side effects. Parents should be informed of these side effects before initiation of treatment. Careful monitoring for signs of side effects, medical intervention when necessary, and lowering of Dex dose during the second half of gestation would minimize the side effects. Maternal serum E3 levels appear useful for prediction of fetal outcome while amniotic fluid steroid levels may not. PMID- 1619018 TI - Persistence of impaired insulin secretion in infant rhesus monkeys that had been hyperinsulinemic in utero. AB - Chronic in utero hyperinsulinemia in the fetal rhesus monkey produces a number of changes in the fetus that are similar to those found in the human infant of the diabetic mother, including macrosomia, selective organomegaly, and altered insulin secretion during the neonatal period. The chronically hyperinsulinemic fetal rhesus model has been used to test the hypothesis that the effects of chronic hyperinsulinemia persist beyond the neonatal period into later life and may, in part, be responsible for the increased prevalence of impaired glucose tolerance or diabetes found in the human infant of the diabetic mother. We report that infant rhesus monkeys that had plasma insulin concentrations of approximately 10 times basal levels (2176 +/- 808 pmol compared to 172 +/- 101 pmol) exhibited reduced insulin secretion during the first 5 months of life. The integrated incremental change in plasma insulin and immunoreactive C-peptide (IRCP) concentration was significantly reduced by approximately 50% in response to i.v. glucose, arginine, and tolbutamide when given at 3, 4, and 5 months of age. The response to glucagon at 2 months of age was equivocal with a significantly reduced insulin response but without the corresponding IRCP reduction. There was no difference between groups in insulin sensitivity as measured at 6 months of age by an i.v. insulin tolerance test. The glucagon and glucose tolerance tests were repeated annually in both groups until the animals were 3 yr of age with no differences in insulin or IRCP secretion being observed. We conclude that chronic in utero euglycemic hyperinsulinemia results in impaired insulin secretion that persists beyond the neonatal period. PMID- 1619019 TI - Treatment of macroprolactinomas with the long-acting and repeatable form of bromocriptine: a report on 29 cases. AB - Twenty-nine patients with macroprolactinomas were treated by monthly intramuscular injections of the long-acting and repeatable form of bromocriptine (Parlodel-LAR) in doses ranging from 50-150 mg. They were divided into two groups: group I consisted of 22 patients who received Parlodel LAR before transsphenoidal adenomectomy; group II was composed of 7 patients with earlier neurosurgery and of 2 patients from group I not cured by transsphenoidal adenomectomy. Duration of therapy varied from 1-12 months, and a total of 104 injections was given. At nadir day, serum PRL levels were situated between less than 1% and 43% of pretreatment values. At day 28 after the first injection, serum PRL levels varied between less than 1% to 139% of initial values. No difference could be detected between the two groups regarding the percent of PRL inhibition. Long-term treatment with Parlodel-LAR resulted in a sustained inhibition of PRL secretion, except for 1 case. Resumption of menstrual cycles occurred in 4 out of 15 women and correction of hypogonadism in 4 out of 14 men. Amelioration of disturbed visual fields was recorded in 3 out of 8 patients. Diminution of the adenoma volume was radiologically documented in 14 out of 22 cases. Only few and mild side effects were recorded. One patient with partial adrenal deficiency suffered from a syncope, but this was prevented by hydrocortisone supplementation during the subsequent Parlodel-LAR administration. In conclusion, Parlodel-LAR proved effective in the treatment of macroprolactinomas, achieving rapid inhibition of PRL secretion, and in some patients amelioration of hypopituitarism, reduction in tumor size, and improvement in visual fields, and caused no serious side effects. It is a valuable preparation to surgery and can also be used in long-term medical therapy. PMID- 1619020 TI - Growth hormone-releasing hormone-like messenger ribonucleic acid and immunoreactive peptide are present in human testis and placenta. AB - Although the sequence of human GH-releasing hormone (GHRH) has been determined, all of the information concerning gene expression has been based on pathological sources of ectopic GHRH, since the only established physiological source of GHRH in humans is the hypothalamus. We recently reported the presence of extrahypothalamic GHRH-like mRNA and immunoreactive material in rat testis and placenta. To determine if human testis and placenta also contain immunoreactive GHRH-like peptides, tissue extracts were analyzed using enzyme-linked immunosorbent assay methodology. Both tissues had detectable quantities of immunoreactive peptide recognized by a monoclonal antibody to synthetic human GHRH-(1-44) (testis, 2.4 ng/g tissue, 0.68 ng/mg protein; placenta, 2.6 ng/g tissue, 0.36 ng/mg protein). The origin of these peptides was confirmed by extracting total RNA from human testis and placenta, with analysis on Northern blots probed with riboprobes for rat hypothalamic GHRH cDNA and human pancreatic tumor GHRH cDNA. Human testis and placenta total RNA both contain an approximately 790-nucleotide RNA species similar in size to that reported in ectopic GHRH-producing human tumors. In addition, two larger hybridization signals were seen at 3000 and 4900 nucleotides. These data suggest that testis and placenta are extrahypothalamic sites of expression of the human GHRH gene. Normal expression of the GHRH gene in extrahypothalamic sites may include transcription of larger mRNA species than those observed in ectopic pathological sources of GHRH expression. PMID- 1619021 TI - Body fat distribution and peripheral insulin sensitivity in healthy men: role of insulin pulsatility. AB - Abdominal fat distribution is associated with insulin resistance in healthy young men. Factors modulating this phenomenon remain unclear. Pulsatile insulin release has been implicated as a potential regulator of insulin action. The relationship of pulsatility of peripheral insulin levels to fat distribution and peripheral insulin sensitivity was examined in 10 healthy men. Fat distribution was determined by the waist to hip ratio. Peripheral insulin sensitivity was assessed by the euglycemic clamp at an insulin infusion rate of 287 pmol/min.m2. Pulsatility of insulin was assessed by sampling every 2 min for 90 min in the basal state. The characteristics of insulin pulses were assessed by the computer program Pulsar. The waist to hip ratio was negatively associated with insulin sensitivity (r = -0.70, P less than 0.05) and insulin pulse interval (r = -0.66, P less than 0.05). The insulin pulse interval was positively correlated with peripheral insulin sensitivity (r = 0.73, P less than 0.05). The insulin interpulse interval was the primary determinant of insulin sensitivity. The increased frequency of insulin pulses may play a role in inducing insulin resistance in individuals with abdominal fat distribution. PMID- 1619022 TI - Immunoreactivity to Yersinia enterocolitica antigens in patients with autoimmune thyroid disease. AB - Recent reports have suggested that Yersinia enterocolitica proteins encoded by a 72-kilobase virulence plasmid (known as release proteins and now identified as YOP2-5) are antigens recognized specifically by patients with Graves' disease and of potential etiological importance in this disorder. To examine this hypothesis, we evaluated immune responses to YOP in patients with autoimmune thyroid disease and in normal controls. Humoral responses to Yersinia were assessed using Western blots of crude Y. enterocolitica membrane proteins, Yersinia release proteins (YOP2-5), and human thyrocyte membranes. Twenty-four of 25 Graves' and 10 of 18 Hashimoto's patients showed reactivity with the release proteins, primarily the 67-, 46-, 36-, and 25-kilodalton bands. However, 17 of 24 normal subjects also demonstrated serological reactivity to the release proteins, and the pattern of reactivity of these sera was similar to that in the thyroid patients. No correlation was noted between serological reactivity to the release proteins and thyroid hormone levels. Patients and controls with serological reactivity to YOP also showed reactivity with Yersinia membranes. In addition to the serological studies, cellular immune responses were determined by peripheral blood mononuclear cell proliferation assays. Cellular reactivity to the release proteins was present in four of five Graves' and both Hashimoto's patients tested, but also in two of six nonthyroid illness patients with serological immunity to the release proteins. Intrathyroidal lymphocytes obtained from two Graves' patients demonstrated marked proliferation in response to the release proteins. These results indicate that there is no unique pattern of serological reactivity against Yersinia membranes or the release proteins in patients with autoimmune thyroid diseases and suggest that any causal relationship between Yersinia infection and Graves' disease may be related to T-cell immunity. PMID- 1619023 TI - Steroid hormone receptors in the adrenal glands of fetal and adult rhesus monkeys. AB - Sex steroid hormone receptors have been identified in the adrenal glands of rodents and may have a role in adrenal function. The highly estrogenic environment during pregnancy has been proposed to influence steroidogenesis by the fetal zone of the primate fetal adrenal gland. In order to determine whether these effects involve receptor-mediated mechanisms, we have examined the concentration and distribution of estrogen receptor (ER), androgen receptor, and progesterone receptor (PR) in the adrenal glands of fetal, immature, and adult rhesus monkeys. Monoclonal antibodies were used for immunocytochemistry (ICC), and in a gradient shift assay, for determination of receptor distribution and concentrations, respectively. There was no difference between the concentrations of ER in the adrenal glands from male and female adult animals (12.4 +/- 2.2, n = 3 and 13.2 +/- 2.0 fmol/mg DNA, n = 7; respectively); however, the concentration of ER in the fetal adrenal glands was markedly lower than in the adults (combined adult 12.7 +/- 1.6, n = 10, and fetal 0.9 +/- 0.4 fmol/mg DNA, n = 7; P less than 0.01). The concentration of ER in the adrenal glands of immature animals was also lower compared to adult animals (6.1 +/- 1.6, n = 6, P less than 0.05). In the adult, ICC revealed that staining for ER was restricted to the cell nucleus and was most dense in the zone fasciculata, with lesser staining in the zona glomerulosa and zona reticularis, and with no detectable staining in the medulla. ER staining was virtually absent in the fetal zone which comprises the major portion of the fetal gland; however, some staining was observed in the narrow definitive zone. The distribution of androgen receptor was similar to that of ER, whereas there was no detectable staining for PR in the adrenals of either adult or fetal animals. We conclude: 1) that the lower concentration of ER in fetal adrenal glands is due to the absence of ER in the fetal zone; 2) the lack of ER and PR in the fetal zone suggests that estrogens and progestins do not influence the growth or function of the fetal zone by receptor-mediated mechanisms; 3) estrogens and androgens may influence the function of the adult adrenal cortex. PMID- 1619024 TI - Abnormal overnight dexamethasone suppression test in subjects receiving rifampicin therapy. AB - We have studied the effects of rifampicin on the overnight 1-mg dexamethasone suppression test usually employed to exclude suspected Cushing's syndrome. Previous observations indicate that in humans, rifampicin profoundly attenuates the biological effects of hydrocortisol and prednisolone, probably by increasing the metabolism of these drugs in the liver. The study was carried out in 16 normal volunteers. All subjects had a normal overnight 1-mg dexamethasone suppression test (468 +/- 86 vs. 32 +/- 21 nmol/L; mean +/- SD). In 8 subjects treated with rifampicin (600 mg) for 10 days, the inhibitory effect of dexamethasone on serum cortisol was completely prevented (575 +/- 114 vs. 434 +/- 82). In the remaining 8 rifampicin-treated subjects, the inhibitory effect of 1, 2, or 3 mg dexamethasone on serum cortisol was not observed. When 4 mg dexamethasone were administered, the serum cortisol level was 193 nmol/L, above the expected normal suppression value. The plasma dexamethasone concentration was very low after rifampicin treatment (range, 1.2-4.8 nmol/L). We conclude that when patients are treated with rifampicin, the standard overnight dexamethasone suppression test not only has no diagnostic value, but can be very misleading. PMID- 1619025 TI - Luteinizing hormone synthesis in cultured fetal human pituitary cells exposed to gonadotropin-releasing hormone. AB - To investigate whether GnRH regulates LH synthesis during human development, pituitary cells from second trimester fetuses were incubated with [35S]methionine ([35S]met) and [3H]glucosamine ([3H]gln) for 48 h with 0, 10(-9), and 10(-7) mol/L GnRH. Immunoassayable (i) LH was measured in media and cellular lysates, and dual label scintillation analysis was used to quantitate incorporation of radiolabeled precursors into cells, trichloroacetic acid-precipitable proteins, and immunoprecipitated LH subjected to electrophoresis. Exposure of cells to GnRH did not affect cellular uptake or incorporation of precursors into proteins, but specifically increased total (secreted plus cellular) LH synthesis. Both GnRH concentrations significantly increased iLH release and enhanced secreted and cellular [3H]gln-LH. The secretion of [35S] met-LH was stimulated only by 10(-7) mol/L GnRH. The proportion of newly synthesized LH that was secreted and the 3H/35S ratio of secreted and cellular LH were uninfluenced by GnRH. Although basal LH synthesis was not sex dependent, total iLH content and GnRH-stimulated LH translation were greater in cells from females than in those from males. Therefore, GnRH regulates LH synthesis by second trimester fetal human gonadotrophs without influencing the proportion of total radiolabeled LH that is secreted. The existence of a sex difference in total iLH content and GnRH stimulated LH translation is consistent with the sexual dimorphism in pituitary LH content occurring during human development. PMID- 1619026 TI - Plasma aldosterone response to upright posture and angiotensin II infusion in aldosterone-producing adenoma. AB - Nineteen patients with primary aldosteronism due to surgically confirmed aldosterone-producing adenoma (APA) were examined to evaluate the response of aldosterone to upright posture and angiotensin II infusion. Upright posture reportedly decreases the plasma aldosterone concentration (PAC) in APA but raises it in idiopathic hyperaldosteronism. However, our findings showed the opposite result, in that the upright posture did not change or raised PAC in 15 of 19 cases (79%). Angiotensin II was infused i.v. at doses from 0.5-2 ng/min.kg body weight in six patients in whom the upright posture raised PAC, but did not raise PAC in all cases. This result supports the assumption that APA is functionally insensitive to angiotensin II. A concomitant rise of ACTH, pretreatment with calcium channel blockade, and other modulating factors may be involved in this PAC rise. Whatever the reason, such a high frequency of patients with increased PAC in APA raises some question about the clinical value of the upright posture test. We believe, then, there is reason to check any interpretation concerning increased PAC in the case of the upright posture test in distinguishing between APA and idiopathic hyperaldosteronism. PMID- 1619027 TI - Thyroid follicular cells produce interleukin-8. AB - Interleukin-8 (IL-8) is a potent proinflammatory cytokine known to be produced by several cell types. To elucidate whether endocrine cells can also make IL-8, we have tested supernatants from eleven thyroid follicular cell primary cultures. IL 8 was readily detected under basal conditions (range 3.4-32.1 ng/ml from 1 x 10(5) cells in 3 days) and was increased 4-20 fold by stimulation with IL-1. TSH and tumor necrosis factor had an inconsistent effect, while gamma-interferon reduced basal and IL-1-stimulated IL-8 production. Since IL-8 can act as a chemoattractant for lymphocytes, these observations may explain in part the accumulation of lymphocytes within the gland in autoimmune thyroiditis. PMID- 1619028 TI - Analysis of the sex-determining region of the Y chromosome (SRY) in sex reversed patients: point-mutation in SRY causing sex-reversion in a 46,XY female. AB - The first and essential step in normal sexual differentiation takes place during the 5th-6th week of gestation. The testis determining factor (TDF) directs the undifferentiated gonad into a testis, which secretes hormones responsible for normal male development. A new candidate for TDF has recently been reported, and it has been called the sex determining region of the Y (SRY). The hypothesis has been supported by the finding of XX individuals with SRY, and two females with 46,XY karyotype and a mutation in SRY. However, XX males without SRY has been reported, and the role of SRY still has to be determined. We have tested three human females with 46,XY karyotype and gonadal dysgenesis and two 46,XX males for the presence of SRY using the polymerase chain reaction and subsequent DNA sequencing. Both 46,XX males contained SRY, whereas one of the 46,XY females had suffered a point mutation in SRY changing a codon for lysine to a stop codon. This information supports the hypothesis that SRY is significant in normal male sex differentiation. The two remaining 46,XY individuals had an intact HMG box, but it is possible that a mutation may be found in a regulatory gene or further downstream in the gene regulatory cascade. Two patients including the one with a mutation in SRY had gonadoblastomas supporting the hypothesis that another gene on the Y-chromosome is involved in the pathogenesis of this neoplasia. PMID- 1619030 TI - Determinants of total body and regional bone mineral density in normal postmenopausal women--a key role for fat mass. AB - In order to determine which clinical, anthropometric, dietary, and biochemical variables are independent predictors of total and regional bone mineral density (BMD) in normal postmenopausal women, a cross-sectional study of 140 normal postmenopausal women has been carried out. Subjects were white, aged 45-71 yr (mean 58 yr), and had no history of disorders or medication use likely to influence bone or calcium metabolism. Multiple regression analysis was used to derive models for total and regional BMD in terms of the other variables measured. The analysis indicated that total body BMD was positively related to fat mass (P less than 0.0001), serum estrone (P = 0.0095) and age at menopause (P = 0.0165), and negatively related to age (P less than 0.0001), 24-h urine calcium (P = 0.0002), sex hormone-binding globulin (P = 0.0003), and serum alkaline phosphatase activity (P = 0.0029) (R2 = 0.61). Similar relationships were found in the subregions of the total body scans and in the lumbar spine and proximal femur, with insulin-like growth factor-1, parity, and age at menarche also being related to BMD at at least two of these sites. Lean body mass was not an independent correlate of BMD at any site once fat mass was taken into account. Muscle strength, physical activity, alcohol intake, and dietary intakes of calcium, sodium and protein did not emerge as significant predictors of BMD in this homogeneous group of postmenopausal women. We conclude that total body fat is the most significant predictor of BMD throughout the skeleton and this relationship is not explicable in terms of either estrone production in fat tissue or the dependence of skeletal load-bearing on fat mass. The mechanism underlying this relationship is an important question to be addressed in bone biology. PMID- 1619029 TI - Oral testosterone undecanoate in the management of delayed puberty in boys: pharmacokinetics and effects on sexual maturation and growth. AB - Therapeutic induction of puberty using oral testosterone (T) undecanoate (TU) 40 mg daily was performed in 4 pubertal boys aged 12.7-17.1 yr with constitutional delayed puberty and/or short stature. Single-dose pharmacokinetics study was performed on matched plasma and saliva samples obtained half-hourly for 10 h after the first dose and then repeated 3 and 6 months later. Treatment was continued for 15-21 months. Peak plasma total T concentration was achieved at 255 +/- 51 (SEM) min after the first 40 mg dose of TU, 300 +/- 76 min at 3 months, and 293 +/- 103 min at 6 months, the levels remaining elevated above baseline for at least 8 h after a single oral dose. Total T levels were initially high (mean 13.0 +/- 2.5; peak 38.7 +/- 4.2 nmol/L) but dropped significantly at 3 months (mean 8.3 +/- 1.8; peak 23.6 +/- 5.6 nmol/L) and at 6 months (mean 9.2 +/- 1.6; peak 24.8 +/- 3.5 nmol/L) paralleled by a dramatic fall in sex hormone binding globulin (73.9 +/- 18.0 to 35.1 +/- 9.7 at 3 month and 29.2 +/- 6.0 nmol/L at 6 month). Mean concentrations of unbound and free T (non-sex hormone binding globulin-bound T, free T, and salivary T) were below the normal adult range and remained unchanged over the same period. Plasma dihydrotestosterone concentrations were elevated after the first dose (mean 5.4 +/- 1.3; peak 11.0 +/ 2.5 nmol/L), the extent of this rise being less after 6 months (mean 4.1 +/- 0.8; peak 7.1 +/- 1.1 nmol/L) as was the case with mean estradiol (51.5 +/- 8.9 to 38.1 +/- 3.7 pmol/L). Signs of virilization progressed to Tanner stage G3 PH2 3 with testicular volumes increasing to 3-4 mL at 12 months, and G4 PH4-5 with further testicular growth to 6-10 mL at 24 months. Height velocity rose from 3.2 +/- 0.3 cm/yr (pretreatment) to 7.2 +/- 1.0 cm/yr in the first year and was maintained at 7.3 +/- 0.4 cm/yr despite cessation of therapy during the second year. Bone age advanced by 1.1 +/- 0.1 yr at 12 months and a further 0.8 +/- 0.3 yr at 24 months. Predicted adult height remained unchanged. No side effects were observed. Our preliminary data suggest that oral TU is a well accepted, effective, and safe treatment for the initiation of male puberty without disproportionate skeletal maturation. Continued pubertal advance was evident after cessation of treatment in all patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1619031 TI - Will postpartum recurrence of Graves' hyperthyroidism become a thing of the past? PMID- 1619032 TI - Postpartum lactational anovulation in a nonhuman primate (Macaca fascicularis): endogenous opiate mediation of suckling-induced hyperprolactinemia. AB - The physiological amenorrhea occurring in suckled females has been associated with both hypopulsatile gonadotropin secretion and hyperprolactinemia. To test whether these phenomena are opiate mediated and whether these effects are dependent on the presence of ovaries, we studied six suckled, lactating cynomolgus monkeys, three with intact ovaries and three that were ovariectomized 14 days postpartum. Frequent blood sampling (every 15 min) was performed at approximately monthly intervals using chronic venous catheters accessed remotely via a jacket and tether system. Each monkey was administered saline or naloxone (2 mg bolus then 2 mg/h) by constant infusion, in alternating 6-h blocks. During saline infusions, PRL concentrations varied markedly in a diurnal pattern with concentrations varying from 30-70 micrograms/L during the day and from 100-200 micrograms/L during the night. In both gonadal intact and ovariectomized groups of monkeys naloxone dramatically suppressed and maintained PRL concentrations at less than 20 micrograms/L irrespective of the time of day or the order of administration. The effects of naloxone on gonadotropin concentrations were much less dramatic. In gonadal-intact monkeys, no effect of naloxone was seen on pulse frequency of either FSH or LH, or on mean LH concentration, and only a slight increase was noted in mean FSH concentrations. In ovariectomized monkeys, naloxone was also without effect on pulsatile LH secretion, although mean LH concentrations were slightly higher during naloxone infusions than during saline infusions (P less than 0.05). From these results, we conclude that opiate peptides are released in response to the suckling stimulus in the cynomolgus monkey and that they mediate the effects of suckling on PRL secretion in both gonadal-intact and agonadal cynomolgus monkeys. The lack of effect of opiate blockade on gonadotropin concentrations suggests that multiple pathways may be involved with the inhibition of the GnRH pulse generator during lactational anovulation. PMID- 1619033 TI - Differences in basal and poststimulation glucose homeostasis in nondiabetic first degree relatives of black and white patients with type 2 diabetes mellitus. AB - Black Americans (blacks) have a higher prevalence and earlier onset of type 2 diabetes than white Americans (whites). To examine metabolic differences in both races, we measured the basal glucose turnover rates (D-]3-3H]glucose technique) and plasma glucose, insulin, and C-peptide levels before and after an oral glucose load in 24 glucose-tolerant black and 14 white female relatives of patients with type 2 diabetes. Eight black and 8 white female subjects with no family history of diabetes served as controls. Mean fasting and postglucose plasma glucose levels were not significantly different between the black and white relatives and the control subgroups. Mean fasting plasma insulin and C peptide levels were slightly greater but not significantly different between the relatives. After oral glucose ingestion, mean incremental integrated plasma insulin areas were significantly (P less than 0.02) greater in the black than the white relatives (70 +/- 14 vs. 29 +/- 6 nM.min). In addition, incremental integrated C-peptide areas were greater in the black than the white relatives (303 +/- 55 vs. 115 +/- 33; P less than 0.005). Similarly, we found significantly greater integrated incremental insulin (61 +/- 11 vs. 22 +/- 3 nM.min; P less than 0.02) and C-peptide (248 +/- 58 vs. 47 +/- 16; P less than 0.005) areas in the black than the white controls, respectively. The estimated basal and postglucose hepatic insulin extraction values, expressed as molar ratios of C peptide and insulin, were not significantly different between the relatives. While basal hepatic insulin extraction was significantly (P less than 0.05) lower in the black controls, the postprandial insulin clearance was not different between the black and white controls. Mean basal hepatic glucose production was greater (P less than 0.02) in the black than the white relatives (2.49 +/- 0.13 vs. 2.02 +/- 0.12 mg/kg.min). Similarly, the black controls had greater hepatic glucose production than the white controls (2.36 +/- 0.15 vs. 1.81 +/- 0.08 mg/kg.min; P less than 0.001). We conclude that basal and poststimulation glucose homeostatic regulation appear to be different in black and white females, regardless of family history of type 2 diabetes. PMID- 1619034 TI - Combined bromocriptine and growth hormone (GH) treatment in GH-deficient children with macroprolactinoma in situ. AB - Experience with PRL-secreting macroadenomas in the pediatric and adolescent population is limited. Although use of synthetic GH after treatment of central nervous system tumors in children without active disease is accepted practice, reports of GH use in patients with central nervous system tumors in situ are rare. Furthermore, the effect of GH on tumor growth is not known. We report GH treatment (10 and 11.5 months), concomitant with bromocriptine (BC; dopamine agonist) therapy in two children, a 15.5-yr-old male and a 15.5-yr-old female, with PRL-secreting macroadenomas in situ. Surgical resection was deemed undesirable because of the risk of major morbidity due to the large size of the tumors and the close proximity to major vessels. Both patients were GH deficient and had heights below the fifth percentile coupled with arrested pubertal progress. During BC therapy, a decrease in tumor size and a reduction in serum PRL levels occurred in both patients, which continued after the addition of GH treatment. Neither patient experienced changes in visual acuity during combined treatment, and both experienced marked improvement in growth velocity. We conclude that in children with PRL-secreting tumors and GH deficiency in whom surgery is not advised, combined treatment with BC and GH appears to be safe and efficacious. To our knowledge, these patients represent the first report of the combined therapeutic use of BC and GH as the primary mode of treatment in children with prolactinoma in situ with documented GH deficiency. PMID- 1619035 TI - Role of the ovary in the synthesis of placental protein-14. AB - Women with absent ovarian function provide an opportunity to investigate the ovarian contribution to secretion of placental proteins (PP), such as PP14, in early pregnancy. We present data on serum PP14 levels in 12 women (median age, 30.5 yr; range, 26-37 yr) with premature ovarian failure (POF) who conceived after ovum donation and embryo transfer with exogenous sex steroid support using transdermal (n = 5) or oral (n = 7) estradiol and vaginal (n = 8) or im (n = 4) progesterone. The women were closely monitored throughout early pregnancy, with measurement of serum levels of estradiol (E2), progesterone (P4), and PP14. Levels of E2 and P4 were entirely normal. Levels of PP14 were significantly subnormal (P = 0.008) in all 12 agonadal women compared with levels of PP14 in a control group of women with normal ovarian function between 6-12 weeks gestation. Basal and peak levels for subjects with absent ovarian function were 40 and 124 micrograms/L, respectively. For each week between 6-12 weeks of pregnancy, the mean serum levels of PP14 for women with normal ovarian function were between 706 940 micrograms/L. These observations support the concept that PP14 arises from the ovary in early pregnancy or that factors under the control of the maternal ovary are involved in its production by the endometrium. PMID- 1619036 TI - A combination of adoptive transfer and antigenic challenge induces consistent murine experimental autoimmune encephalomyelitis in C57BL/6 mice and other reputed resistant strains. AB - Adoptive EAE was induced in SJL mice by the transfer of MBP-primed and in vitro stimulated donor lymph node cells into naive syngeneic recipients. Priming donor mice with OVA instead of restimulating MBP-primed donor cell with OVA resulted in no transfer of EAE. This apparent lack of disease, however, could be overcome if the recipients were subsequently challenged with MBP. When this transfer challenge technique was applied to BALB/c and C57BL/6 mice, these reputed (MBP)EAE-resistant strains developed consistent and severe disease similar to that seen in susceptible strains. In fact, a survey of eleven (MBP)EAE-resistant strains, defined on the basis of their inability to mount an encephalitogenic response in recipient mice following the transfer of MBP-primed and in vitro activated lymph node cells, revealed that EAE could be induced in all these strains. Since the surveyed strains represented a wide spectrum of genetic backgrounds as well as the common MHC congenic haplotypes (H-2b,d,k,m,r,s,v), it is concluded that the machinery for recognition of MBP, i.e. MHC genes and the appropriate T cell receptors, is functionally intact in these resistant mice. While MHC and T cell receptor genes are required for T cell responses, they are not the limiting factors that confer resistance in murine EAE. PMID- 1619037 TI - The pineal hormone melatonin exaggerates development of collagen-induced arthritis in mice. AB - We have previously shown that constant darkness enhances autoimmunity to type II collagen (CII) and exaggerates development of collagen-induced arthritis (CIA) in DBA/1 mice. This effect was suggested to be mediated via the major hormone of the pineal gland, melatonin, since this hormone (1) is known to be strongly dependent on environmental lighting and (2) has been reported to affect the immune function. The present study was performed in order to clarify if melatonin could account for the previous observation that mice kept in darkness had a more pronounced development of CIA. First, DBA/1 mice kept in constant darkness were analysed for serum melatonin levels. An increase in background levels in comparison to mice kept in a normal dark/light cycle or in constant light was recorded. Then, different groups of mice (kept in constant light in order to minimize endogenous melatonin levels) were immunised with rat CII to induce arthritis and injected with melatonin. Melatonin injections were performed daily (1 mg/kg b.w.) in the afternoons (at 4 p.m.) for 10 days at two different periods: day 1-10 after collagen injection, or at the onset of the disease (day 30-39). Mice injected with melatonin at day 1-10 developed a more severe arthritis while those injected at onset did not differ significantly from the corresponding controls. Our results support the hypothesis that the pineal gland can exaggerate the development of CIA via a high release of melatonin, probably via enhancement of T-cell priming. PMID- 1619038 TI - An immunohistochemical study of phospholipase A2 in peripheral nerve during Wallerian degeneration. AB - Antiserum raised against purified Crotalus adamanteus venom phospholipase A2 (PLA2) was used to localise the enzyme in normal and crushed sciatic nerve to determine the effect of nerve trauma on PLA2 distribution in the PNS. The tissue was Bouin's fixed, and stained immunohistochemically using the Vectastain ABC technique. Anti-PLA2 antiserum showed weak reactivity with normal rat myelin, while only 'resident' macrophages stained in normal mouse sciatic nerve. Post crush, in the mouse, myelin staining was localised close to the crush site, with strong lysosomal staining within both 'resident' and invading haematogenously derived macrophages. In the rat, myelin sheaths stained strongly throughout the nerve very soon after crush, but no macrophages were detected using these antisera. Paranodal myelin and some Schmidt-Lanterman incisures were the first regions of the sheath to show an increase in PLA2 staining post-crush, areas where the first ultrastructural changes occur in myelin after trauma, with staining of compact myelin closely following. Our findings support the idea that PLA2 may be involved in the early process of myelin breakdown seen in Wallerian degeneration. PMID- 1619039 TI - Role of arachidonic acid metabolism on corticotropin-releasing factor (CRF) release induced by interleukin-1 from superfused rat hypothalami. AB - The present work shows that the corticotropin-releasing factor (CRF)-releasing activity of interleukin-1 (IL-1) is partially inhibited by a phospholipase A2 (mepacrine) or a cyclooxygenase (indomethacin) inhibitor, but is not affected by inhibition of the lypoxygenase pathway with norhydroguaiaretic acid. These results indicate that the metabolism of arachidonic acid plays an important role as mediator of the effects of IL-1 on CRF release. It is also shown that products of the cyclooxygenase activity such as prostaglandins can stimulate CRF secretion by a direct action on the hypothalamus. Whereas PGE2 failed to induce increases on CRF release, PGF2 alpha stimulated in a dose-dependent manner (21-340 nM), the CRF release from continuous perifused hypothalami. It is suggested that PGF2 alpha could be involved as a messenger in the hypothalamic CRF secretion induced by IL-1. PMID- 1619040 TI - Interleukin-1 activity in lesioned peripheral nerve. AB - The cytokine interleukin-1 (IL-1) is involved in a wide range of inflammatory and immune responses. As such, IL-1 could play a role in peripheral nerve repair mechanisms. Specifically, by its already established properties as a regulator of nerve growth factor (NGF) synthesis, and as a chemotactant to macrophages. We examined, therefore, IL-1 production in injured mouse peripheral nerve. Injured nerve segments were incubated in serum free medium to produce conditioned medium (CM) that was then tested for IL-1 activity in a thymocyte proliferation assay. CM induced thymocyte proliferation in a dose-dependent manner. Proliferation was inhibited by the M20 IL-1 inhibitor, the IL-1 receptor antagonist, and antisera raised against recombinant mouse IL-1 alpha. Inhibitions produced by these three specific inhibitors of IL-1-induced thymocyte proliferation strongly suggest that proliferation induced by CM was mediated largely by IL-1 secreted by non-neuronal cells residing in the damaged nerve. IL-1 activity was detected within hours after lesion, and 1 week thereafter. The rapid and prolonged production of IL-1 indicates that IL-1-dependent mechanisms can play roles in the response of the peripheral nerve to injury: degeneration and regeneration. The regulation of NGF synthesis, and the recruitment of white blood cells, macrophages in particular, from blood into the damaged nerve tissue, are two such mechanisms. PMID- 1619041 TI - Functional organization of vagal reflex systems in the brain stem of the goldfish, Carassius auratus. AB - The coordination of secretory and motor responses to food within the alimentary canal requires well organized brain stem reflex systems. In the goldfish, Carassius auratus, three vagal reflex systems control three phases of ingestion and digestion. The orobranchial system sorts food from substrate, the pharyngeal chewing organ prepares items deemed to be food for digestion and absorption, and the abdominal system regulates the digestion of food. Each system is represented in the central nervous system by separate sensory and motor nuclei. The aim of the present study was to determine whether the interrelationships among the vagal sensory and motor nuclei reflect the peripheral organization. The sensory nucleus of each vagal system was injected with the neuronal tracer horseradish peroxidase (HRP), in separate cases. HRP injections into the vagal lobe sensory layers (orobranchial system) labeled fibers projecting topographically to the vagal lobe motor layer, but not at all to the pharyngeal or abdominal motor nuclei. Similarly, injections of HRP into the pharyngeal and abdominal sensory nuclei selectively labeled nerve fibers projecting to the pharyngeal and abdominal motor nuclei, respectively. All injections resulted in labeled fibers and/or cells in the lateral reticular formation, and in fibers ascending in the secondary gustatory-visceral tract. Gustatory information from the pharynx is apparently processed in the same brain stem system as pharyngeal general visceral information, suggesting that functional or regional characteristics of visceral sensory information may be more important for brain stem processing than the traditional "special" (gustatory) versus "general" visceral dichotomy. These results indicate that anatomically and functionally separate reflex systems exist within the goldfish vagal visceral nuclei. PMID- 1619042 TI - Anatomical organization of the brainstem octavolateralis area of the oyster toadfish, Opsanus tau. AB - Anatomical studies were undertaken to analyze the brainstem organization of the auditory, vestibular, and lateral line nuclei in a teleost, the oyster toadfish, Opsanus tau. Neuronal cytoarchitectonics and horseradish peroxidase label of cranial nerves were utilized to delineate the borders of the five octavus and two lateralis brainstem nuclei. Each of the eight octavolateralis nerves were labeled individually to compare and contrast their central projections. Projections of the three semicircular canals were found to be largely overlapping. Terminal fields were observed within the eminentia granularis and in each of the octavus nuclei. The nucleus anterior octavus was reciprocally innervated by the semicircular canals and the saccule. The canals terminated heavily in the ventral portions of the anterior octavus, whereas the saccule terminated extensively in the dorsal nuclear portions. The saccule also distributed terminals throughout the octavus cell column, including a light terminal field within the dorsal, medial, and anterior portions of the descending octavus nucleus, a region densely innervated by this end-organ in other species. These results suggest that the anterior octavus nucleus may have a dual function. The dorsal portions may be an auditory relay nucleus, whereas the ventral portions may subserve vestibular function. Utriclar and lagenar afferents also terminated throughout the octavus cell column. Afferents of the anterior and posterior lateral lines ended within the eminentia granularis and the lateral line nuclei. Semicircular canal afferents and lateral line afferents appeared completely segregated within the eminentia. The above results are useful as an aid in the understanding of an ongoing, comprehensive functional analysis of auditory and vestibular mechanisms in toadfish and complement previous work on the efferent vestibular and sound producing motor systems. Examination of toadfish contributes to a more general and complete overview of the octavolateralis area of teleosts and the eventual identification of primitive and derived patterns of octaval organization. Additionally, this work may permit the further demonstration of species-typical characters that may indicate adaptations to particular behavioral repertoires. PMID- 1619043 TI - Ultrastructure of the periaqueductal grey matter of the rat: an electron microscopical and horseradish peroxidase study. AB - The neurons of the mesencephalic periaqueductal grey substance (PAG) in the rat are small and medium sized. The cells are frequently located in small clusters, without interdigitating glial elements and may be connected by direct membrane appositions or by gap junctions. The inner zone of the PAG is cell poor. In many cases, the cytoplasm of the cells is filled with extensive rough endoplasmic reticulum, free ribosomes, Golgi apparatus, and large lysosome-like granules. The nuclei show large indentations. The cells have a high nucleus-cytoplasm ratio. The neuropil is very extensive and particularly rich in large numbers of small unmyelinated axons, dendrites, axonal varicosities, and synaptic connections. Myelinated fibres are relatively scarce. The orientation of the fibres was studied in transverse and horizontal sections, in combination with HRP track tracing experiments. It appeared that throughout the PAG most of the fibres were orientated longitudinally. Quantitation showed that most fibres were present in the inner zones of the PAG. Moreover, the diameter of the fibres adjacent to the aqueduct was smaller than that of the fibres in the peripheral parts of the PAG. The thin unmyelinated fibres made extensive synaptic connections within the PAG. Many synaptic varicosities were found in the neuropil of the PAG. There were four types of synaptic varicosities, characterized by different populations of clear and dense-core secretory granules and by the different morphology of the synaptic specializations. In general, the different types of varicosity were homogeneously distributed in the different parts of the PAG. Electron dense secretory granules, when present, were located at some distance from the synaptic junction. Serial sections revealed varicosities which contained only dense-core secretory granules, without synaptic specializations. The dendrites of PAG neurons generally lacked synaptic spines. Many dendrites, particularly those of neurons located in the peripheral parts of the PAG, were directed toward the aqueduct. The present study shows that the PAG is a very complex brain area. The crisscrossing of axons and dendrites with synaptic connections at considerable distances from the cell bodies render it very difficult to unravel the relationships between the possible sources and destinations of ongoing information. This structure complicates the search for relationships between the functional organization and the cytoarchitectural borders in the PAG area. PMID- 1619044 TI - Dorsal mesencephalic projections to pons, medulla, and spinal cord in the cat: limbic and non-limbic components. AB - The vertebrate dorsal mesencephalon consists of the superior colliculus, the dorsal portion of the periaqueductal gray, and the mesencephalic trigeminal neurons in between. These structures, via their descending pathways, take part in various behavioral responses to environmental stimuli. This study was undertaken to compare the origins and trajectories of these pathways in the cat. Injections of horseradish peroxidase into the cervical spinal cord and upper medullary medial tegmentum retrogradely labeled cells mainly in the contralateral intermediate and deep superior colliculus, and in the ipsilateral dorsal and lateral periaqueductal gray and adjacent tegmentum. Only injections in the medullary lateral tegmental field labeled mesencephalic trigeminal neurons ipsilaterally. Autoradiographic tracing results, based on injections across the dorsal mesencephalon, revealed three efferent fiberstreams. A massive first fiberstream (limbic pathway), consisting of thin fibers, descended ipsilaterally from the dorsal and lateral periaqueductal gray and adjacent superior colliculus through the mesencephalic and pontine lateral tegmentum, terminating in these areas as well as in the ventral third of the caudal pontine and medullary medial tegmentum. A few fibers from the dorsal periaqueductal gray matter (PAG) were distributed bilaterally to the dorsal vagal, solitary, and retroambiguus nuclei. The second fiberstream (the predorsal bundle) descended contralaterally from the superior colliculus (SC) and consisted of both thick and thin labeled fibers. The thin fibers terminated bilaterally in the dorsomedial nucleus reticularis tegmenti pontis and the medial half of the caudal medial accessory inferior olive. The thick fibers targeted the contralateral dorsal two thirds of the caudal pontine and medullary medial tegmental fields, and the facial, abducens, lateral reticular, subtrigeminal, and prepositus hypoglossi nuclei. A few fibers recrossed the midline to terminate in the ipsilateral medial tegmentum. Caudal to the obex, fibers terminated laterally in the tegmentum and upper cervical intermediate zone. From the lateral SC, fibers terminated bilaterally in the lateral tegmental fields of the pons and medulla and lateral facial subnuclei. The third fiberstream (mesencephalic trigeminal or Probst tract) terminated in the supratrigeminal and motor trigeminal nuclei, and laterally in the tegmentum and upper cervical intermediate zone. In summary, neurons in the PAG and in the deep layers of the SC give rise to a massive ipsilateral descending pathway, in which a medial-to-lateral organization exists. A similar topographical pattern occurs in the crossed SC projections. The possibility that these completely different descending systems cooperate in producing specific defensive behaviors is discussed. PMID- 1619045 TI - Development of catecholaminergic, indoleamine-accumulating and NADPH-diaphorase amacrine cells in rabbit retinae. AB - We have investigated the ontogeny of four classes of amacrine cells in the rabbit retina. In particular, the distribution, number, soma diameter, dendritic field diameter, and pattern of dendritic stratification were studied in catecholaminergic (CA) and indoleamine-accumulating (IA) amacrines and in two classes of nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase amacrine cells. The first CA and IA cells are observed on the 27th postconceptional day (27PCD) and the first NADPH-diaphorase cells on 28PCD. These first cells are concentrated in the central part of the visual streak, and at subsequent ages, cells in this part of the streak have larger somata and more mature dendritic fields than those elsewhere, supporting the notion that the peak density region is a developmentally advanced part of the retina. Throughout development, amacrine cells of all classes are concentrated in the visual streak, with their density reaching minima at the superior and inferior retinal margins. As their total number increases, the difference in cell density between the streak and the periphery decreases, presumably because proportionately more cells are added at the periphery. Their total number peaks around 42PCD, followed by a decline of 12-31% to adult values. Once the peak number of cells has been reached, the difference in cell density between the streak and periphery begins to increase. The rate of this increase is closely correlated with the increase in retinal area. This redistribution of amacrine cells, as well as a greater expansion of their dendritic fields in peripheral retina, is almost certainly the product of nonuniform retinal expansion. PMID- 1619046 TI - Distribution of immunoreactivity for gamma-aminobutyric acid in the salamander olfactory bulb. AB - Intrinsic neurons provide inhibitory synaptic input to mitral (and tufted) output cells within several laminae of the olfactory bulb. In rodents, the two main types of intrinsic neurons are granule and periglomerular cells, both of which contain gamma-aminobutyric acid (GABA). In the present study, immunocytochemical techniques were used to determine whether intrinsic neurons in the salamander olfactory bulb might also contain GABA. With the aid of two antisera to different GABA-conjugates, immunoreactivity for GABA was localized within the olfactory bulb laminae. In the glomerular layer, periglomerular cells, which were strongly immunoreactive, were concentrated in clusters along the border with the olfactory nerve layer. Dendrites of the cells encircled nearby glomeruli and were presumably a primary source of intraglomerular processes that were also stained. In the subglomerular region and external plexiform layer, relatively few immunoreactive cells were observed, most of which appeared to be periglomerular and tufted cell types with glomerular dendrites. Throughout the external plexiform and mitral cell layers, however, a dense matrix of spiny processes and puncta was stained, outlining large, unstained dendrites derived from the large, unstained cell bodies of mitral cells. The spiny processes and puncta appeared to be derived from granule cells, which were the most abundant immunoreactive cells in the bulb. Granule cell bodies filled the granule cell layer. In tissue fixed with 0.1-0.2% glutaraldehyde, staining in the olfactory bulb laminae was blocked by preadsorption of the two antisera with glutaraldehyde-conjugated GABA-bovine serum albumin. The staining therefore appeared to be specific for fixed GABA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619047 TI - Segmental distribution and peptide content of primary afferent neurons innervating the urogenital organs and colon of male rats. AB - Many visceral afferent neurons contain peptides, which have been proposed as histochemical markers for nerve pathways of particular targets or as transmitter candidates. The former possibility was investigated in the present study. Primary afferent neurons which project to the urinary bladder, distal colon or penis of rats, and the colon of cats were labelled with retrogradely transported fluorescent dyes (Fast Blue, True Blue, or Fluoro Gold). One to six weeks after dye injection into the organs, lumbosacral dorsal root ganglia were removed, treated with colchicine, and processed for immunohistochemical identification of five peptides. Dye-labelled neurons were distributed in an organ-specific manner in the lower lumbosacral ganglia, where colon afferent neurons were almost exclusively found in S1 ganglia, penis neurons primarily in L6, and bladder neurons at both levels. Substance P- (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide- (VIP), enkephalin- (ENK), and somatostatin (SOM) immunoreactivity (IR) were detected in neurons in all lumbosacral ganglia but only some of these peptides were present in a large percentage of labelled neurons. The numbers of peptide-containing neurons innervating each organ were CGRP greater than SP greater than VIP greater than ENK greater than SOM; however some differences were observed in the relative proportions of these neuronal populations between upper lumbar and lower lumbosacral ganglia and between different organs. The major difference seen at the upper lumbar level was amongst the SP-IR neurons, which were common (25-30%) amongst bladder and colon afferent neurons but absent in penis neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619048 TI - Distribution of buccalin-like immunoreactivity in the central nervous system and peripheral tissues of Aplysia californica. AB - The neuropeptide buccalin A was originally purified and sequenced from a nerve muscle system used in feeding-related behaviors of Aplysia californica in which it has been proposed that it acts as a modulatory cotransmitter. The distribution of buccalin-like immunoreactivity in the central ganglia and in peripheral tissues of Aplysia californica was examined by whole mount immunohistochemical techniques. Immunoreactive material was located in specific cell bodies and clusters of neurons in each of the ganglia. Immunoreactive fibers were present in each of the connectives between ganglia, in tracts coursing through the ganglia, and in the majority of the peripheral nerves. Most fibers were smooth in contour, but some had regularly spaced swellings. Varicosities containing immunoreactive material were located on specific neuronal somata and on certain tissues associated with the feeding, circulatory, digestive, and reproductive systems. The specific and widespread distribution of buccalin-like immunoreactivity supports the hypothesis that members of the buccalin peptide family act as neuromodulators or neurotransmitters in a variety of central and peripheral circuits in Aplysia. PMID- 1619049 TI - Differential calbindin-like immunoreactivity in the brain stem auditory system of the chinchilla. AB - Calbindin is a 28 kD calcium-binding protein found in neural tissue. Although its functional role in neurons is unknown, it has been proposed that calbindin is involved in intracellular buffering and could therefore influence temporal precision of neuronal firing. In the barn owl, calbindin-like immunoreactivity was found to be selectively present in brain stem auditory pathways used to process interaural time differences, but was absent from the interaural intensity pathway. The present study demonstrates calbindin immunoreactivity in the auditory brain stem of the chinchilla, a rodent with exceptionally good low frequency hearing. In the superior olivary complex and periolivary areas, immunoreactivity was divided between neuropil labeling in the lateral and medial superior olives and dorsomedial periolivary nucleus, and labeling of the somata of the medial and ventral nuclei of the trapezoid body and anterolateral periolivary nucleus. Strong immunoreactivity was observed in the ventral and dorsal divisions of the ventral nucleus of lateral lemniscus somata and the ventral division's columnarly organized fiber plexus. The dorsal nucleus of the lateral lemniscus was void of immunoreactivity. Virtually all principal neurons of the sagulum showed darkly labeled somata surrounded by a densely labeled fiber plexus. Immunoreactivity in the inferior colliculus was primarily limited to the paracentral nuclei, with only an occasional labeled cell in the central nucleus. In conclusion, although selective labeling of calbindin in the mammalian auditory brain stem is impressive, no distinctive labeling of a functionally defined timing pathway was apparent as reported previously in the barn owl or electric fish. PMID- 1619050 TI - Correlation of filiform hair position with sensory afferent morphology and synaptic connections in the second instar cockroach. AB - An attempt is made to relate the distribution of filiform hairs on the cercus of the second instar cockroach, Periplaneta americana, to the morphology and patterns of synaptic connectivity of their afferents. We studied the most distal 25 of the 39 filiform hairs which are commonly present. Filiform afferent arborizations were stained by cobalt filling from the cell body in the cercus. Three fundamental arbor types were found, two similar to those of the first instar medial (M) and lateral (L) afferents, and a third, novel type. L-type arbors could be divided into four subtypes. The most obvious correlate of arbor type is the circumferential position of the hair on the cercus. The proximodistal position of the sensillum within each cercal segment is also a determinant of its arbor. By comparison of hair positions and afferent morphologies, we were able to ascribe homologies between the second instar hairs and members of adult longitudinal hair columns. The patterns of monosynaptic connections between afferents and giant interneurons (GIs) 1, 2, 3, 5, and 6 were determined by recording synaptic potentials in GIs evoked by direct mechanical displacement of individual filiform hairs. Latency from stimulus onset to the rise phase of the first excitatory postsynaptic potential (EPSP) was used as the criterion of monosynapticity. The EPSP amplitudes of the two original L and M afferents are halved in the second instar, in the absence of a significant decrease in GI input resistance. The other afferents can be divided into two basic classes: those which input to GI5 (M-type), and those which input to GI3 and GI6 (L-type). The former is correlated with a central or medial position, while the latter is associated with a group of afferents situated laterally on the cercus. In segments 3 and 4, input to GIs 1 and 2 also correlates with a medial cercal position, however, in the more proximal segments 5 and 6, afferents at all positions input to these interneurons. The occurrence of afferents of identical morphology and similar connectivity in equivalent positions in different segments suggests that each sensory neuron is determined by its two-dimensional position within a segment. The presence of afferents with the same morphology which display proximodistal differences in synaptic connectivity, and of other afferents which have M-type connectivity despite L-type morphology, means that anatomy is generally a poor predictor of synaptic connectivity. PMID- 1619051 TI - Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: a light and electron microscopic study of the thalamostriatal projection in relation to striatal heterogeneity. AB - The organization of the thalamostriatal projections arising from the centromedian (CM) and parafascicular (Pf) thalamic nuclei in the squirrel monkey (Saimiri sciureus) was studied at both light and electron microscopic levels. Following selective injections of the anterograde axonal tracer Phaseolus vulgaris leucoagglutinin (PHA-L) into the CM or Pf, patterns of terminal arborization within the striatum were compared to the biochemical heterogeneity of the striatum as revealed by immunohistochemical staining for the calcium-binding protein calbindin D-28k (CaBP), and histochemical staining for the enzymes acetylcholinesterase (AChE) and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase). The PHA-L-labeled axon terminals within the striatum were further analyzed at the ultrastructural level to characterize their pattern of synaptic organization. Dense and heterogeneous terminal fields occur in the "sensorimotor" territory of the striatum after CM injections, or in the "associative" striatal territory following Pf injections. In the associative territory labeled axons arborize in a diffuse manner predominantly within areas enriched with CaBP, AChE, or NADPH-diaphorase, representing the matrix compartment, and tend to avoid areas poor in these substances, corresponding to the patch/striosome compartment. In the sensorimotor territory labeled axons form bands that occupy a subregion of the NADPH-diaphorase-rich zone in the putamen. The terminal pattern of the CM-striatal projection suggests the existence of a more complex mosaic organization within the sensorimotor territory. Ultrastructural analysis of PHA-L-labeled elements within the striatum reveals that both CM and Pf projections form asymmetric synapses upon dendrites and spines of striatal cells. A total of 339 PHA-L-labeled boutons were examined after CM injections and compared to 293 boutons following Pf injections. After CM injections, 29% of PHA-L-labeled terminals form synapses on dendritic spines and 66% on dendritic shafts, whereas after Pf injections only 12% of synapses occur on dendritic spines compared to 81% on dendritic shafts. Labeled terminals forming axosomatic or axoaxonic synapses were not seen within the striatum following either CM or Pf injections. It is concluded that in the squirrel monkey: 1) Pf-striatal fibers profusely arborize within the matrix compartment of the associative territory, 2) CM-striatal fibers form bands that occupy a subregion of the NADPH-diaphorase-rich zone within the sensorimotor territory, and 3) that both Pf- and CM-striatal projections establish asymmetric synapses with dendrites and spines of medium-sized spiny cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1619052 TI - The calcium binding proteins parvalbumin and calbindin-D 28K form complementary patterns in the cat superior colliculus. AB - Parvalbumin (PV) and calbindin-D 28K (CaBP) are calcium binding proteins involved in calcium regulation in the brain. In some regions they coexist in the same neuron, while in other regions they are found in different cell types. We have studied the distribution and morphology of PV labeled neurons in the cat superior colliculus (SC) with antibody immunocytochemistry and compared this labeling to that of CaBP. PV neurons were concentrated in a dense tier within the deep superficial gray and upper optic layers. Scattered PV neurons also were found within the deep layers of SC. By contrast, CaBP neurons were concentrated in three tiers: one within the zonal and upper superficial gray layers, a second within the deep optic and upper intermediate gray layers (IGL), and a third within the deep gray layer. The distribution of PV neurons is thus complementary to that of CaBP neurons, with the CaBP cell tiers bordering the dense tier of PV neurons. PV neurons varied in size and morphology. The average diameter of labeled cells was 20 microns, almost twice the size of CaBP neurons. The cells were predominantly round, vertical fusiform, or stellate, and included the very large neurons found scattered in the IGL. Horseradish peroxidase injections into the lateral geniculate nucleus, the lateral posterior nucleus, the opposite superior colliculus, the dorsal lateral pontine gray nucleus, and two descending pathways--the crossed predorsal bundle and the tecto-ponto-bulbar tracts--each labeled SC neurons that were also labeled by PV. A large percentage (84%) of projection neurons contained PV. This result also differs from CaBP neurons in SC, most of which are interneurons. Two antigen double-label experiments did not produce any cells that contained both PV and CaBP. The two calcium binding proteins thus reveal a unique sublaminar organization in SC that consists of alternating small cell interneuron groups and large cell projection neuron groups. PMID- 1619053 TI - Serotoninergic projections from the raphe nuclei to the preoptic area in sheep as revealed by immunohistochemistry and retrograde labeling. AB - A retrograde tracer, fluorogold, was injected into the sheep preoptic area in order to demonstrate the origin of the serotoninergic fibers observed in this area. Within the raphe nuclei, retrogradely fluorogold-labeled neurons were observed mainly in the median raphe nucleus (B8), groups B6/B5, and in the area lateral to the nucleus interpeduncularis (group S4), but not in the dorsal raphe nucleus. About 50% of these fluorogold-containing neurons were immunostained with a specific antiserum raised against serotonin. Double-labeled neurons (serotonin immunoreactive and fluorogold containing neurons) represented less than 20% of the whole number of serotoninergic neurons. We concluded that a few serotoninergic neurons in the median raphe nucleus and in groups B5/B6 and S4 project to the preoptic area. Moreover, these nuclei contained non-serotoninergic neurons which project to the same area. These results give new information on the serotoninergic innervation of the preoptic area in the sheep. PMID- 1619054 TI - Mechanisms of metastasis. AB - The role of dermatologists in the diagnosis and treatment of skin cancer continues to increase. Consequently, they will more frequently be involved in the diagnosis, treatment, and management of patients with metastatic or potentially metastatic tumors. Squamous cell carcinomas and malignant melanomas are frequently seen in dermatologic practices and have the capability to metastasize. Metastases are the result of a complex process that is characterized by a sequence of steps, each of which requires acquisition by the malignant cell of key biologic properties. The metastatic sequence can be conceptualized as detachment from the primary tumor followed by invasion, intravasation into a vessel, circulation, stasis within a vessel, extravasation, invasion of the recipient tissue bed, and ultimately proliferation. The basic steps of the metastatic sequence are described as well as how these steps and other tumor cell adaptations can affect the clinical patterns of metastasis. Finally, practical applications of the understanding of these principles of metastasis are discussed. PMID- 1619055 TI - Diffuse neonatal hemangiomatosis treated successfully with interferon alfa-2a. PMID- 1619056 TI - Zosteriform speckled lentiginous nevus. PMID- 1619057 TI - Erythema ab igne: treatment with 5-fluorouracil cream. PMID- 1619058 TI - Clinical evaluation of etretinate for the treatment of canine solar-induced squamous cell carcinoma and preneoplastic lesions. AB - BACKGROUND: Tumors of the skin and subcutaneous tissue account for 30% of all canine neoplasms. Canine solar-induced squamous cell carcinoma (SCC) is the most frequently reported canine cutaneous neoplasm. OBJECTIVE: The purpose of this study was to provide preliminary observations on the safety and efficacy of etretinate for the treatment of solar-induced SCC and associated preneoplastic lesions in dogs. METHODS: Etretinate was administered to 10 dogs at 1 mg/kg twice daily for a minimum of 90 days. RESULTS: Clinically, two dogs showed complete resolution of their preneoplastic lesions, three dogs had partial responses, two dogs maintained stable disease, and three dogs showed progression of lesions after 90 days of etretinate administration. Three dogs showed histologic improvement, four dogs showed no changes, and three dogs showed evidence of progressing SCC. Treatment-related biochemical abnormalities included reversible hypertriglyceridemia and transient serum liver enzyme elevations in three dogs. CONCLUSION: These preliminary findings suggest that etretinate, at the dosage administered, may provide therapeutic efficacy for solar-induced preneoplastic lesions in the dog, particularly for those multifocal lesions not easily managed by local methods of therapy. PMID- 1619059 TI - Pool palms. PMID- 1619060 TI - Evaluation of anthralin for mycosis fungoides. PMID- 1619061 TI - Localized unilateral hyperhidrosis: eccrine nevus. PMID- 1619062 TI - Starvation-associated pruritus: a clinical feature of eating disorders. PMID- 1619063 TI - Acetaminophen-induced progressive pigmentary purpura (Schamberg's disease). PMID- 1619064 TI - Metastasis. PMID- 1619065 TI - Approved drugs for unapproved indications: some clouds on the horizon. PMID- 1619066 TI - Dermabrasion of Hailey-Hailey disease and Darier's disease. PMID- 1619067 TI - Screening photoprotective agents against UVA radiation. PMID- 1619068 TI - Serum aminoterminal propeptide of type III procollagen in the management of methotrexate-induced fibrogenesis. PMID- 1619069 TI - Grafting of leg ulcers with undifferentiated keratinocytes. PMID- 1619070 TI - Malignant melanoma of the eyelid. A report of eight cases and a review of the literature. AB - BACKGROUND: Because of the relatively rare occurrence of malignant melanoma (MM) of the eyelid, prognostic factors in relation to survival in these patients have not been established. OBJECTIVE: Our purpose was to examine prognostic indicators in relation to survival in patients with MM of the eyelid. METHODS: All patients seen at UCLA Medical Center with MM of the eyelid as well as all cases reported in the literature were reviewed retrospectively. RESULTS: The data obtained from 47 total cases seen at UCLA Medical Center revealed a significant disadvantage in 5-year survival for those patients with MM involving the lid margins in comparison to those without lid margin involvement. CONCLUSION: Our review suggests that melanoma involving the eyelid margin and conjunctiva has a worse prognosis than melanomas of the eyelid that do not involve the conjunctiva. We can make no predictions in regard to the benefits of narrow versus wide surgical margins in the treatment of these patients. PMID- 1619071 TI - Influence of cumulative sun exposure on the prevalence of common acquired nevi. AB - BACKGROUND: Conflicting evidence exists on the relation between sun exposure and the number of common acquired nevi. The increase in the number of common acquired nevi until early adulthood and their greater concentration on sun-exposed areas suggested that the growth of common acquired nevi is promoted by UV radiation. Nevertheless, it was noticed that although solar exposure accumulates with age, the number of common acquired nevi decreases after the third decade. OBJECTIVE: Our purpose was to examine the relation between the prevalence of common acquired nevi and accumulative sun exposure. METHODS: The number of common acquired nevi on 128 patients with multiple solar keratoses (SK) was compared with their number on 82 control subjects. The existence of SK served as a biologic marker for long term solar effects. RESULTS: On patients with SK we counted 1285 nevi (mean 10.0 nevi per person) and on control subjects, 1521 nevi (mean 18.5 nevi) (p = 0.0046; Kruskal-Wallis test). The finding that persons exhibiting signs of accumulating sun effects have fewer nevi was maintained irrespective to differences of gender, occupation, and complexion. CONCLUSION: Our data suggest that accumulating solar effects may contribute to the natural maturation and elimination of common acquired nevi in late adulthood. PMID- 1619072 TI - Sun exposure in Australian adolescents. AB - BACKGROUND: Little information is available on the sun-related behavior of teenagers despite the considerable resources spent to decrease sun exposure in this age group. OBJECTIVE: Our purpose was to describe the sun exposure behavior of Australian adolescents and define characteristics that predict use of sun protection. METHODS: Cross-sectional study of a random sample of 972 school students 13 to 15 years of age from three different locations in Australia (two urban and one rural) using a diary to document sun exposure and sun protection on two consecutive weekends. RESULTS: More than 80% of adolescent boys in each place and more than 60% of adolescent girls in both of the large cities spent more than 2 hours outdoors during the peak ultraviolet (UV) periods on each weekend. Neither sunscreen nor hats were used for more than half the time spent in the sun; however, shirts were worn most of the time. Students who wore hats were more likely to be boys (odds ratios [OR] = 2.2, 95% confidence intervals [CI] 1.40 to 3.44) and live in the rural region (OR = 4.6, 95% CI 2.36 to 9.04). Students who used sunscreen tended to have skin that sunburned easily (OR = 3.2, 95% CI 1.27 to 7.88) and score highly on the knowledge questions (OR = 2.9, 95% CI 1.46 5.69). This model was not a good predictor of behavior on a subsequent weekend, possibly because behavior was highly variable, with 35% to 50% of students changing their pattern of protection use from one weekend to the next. CONCLUSION: Adolescents spend long periods on summer weekends in the sun and do not follow recommended sun protection guidelines. The high variability of sun related behavior makes modeling and consequent development of education programs a difficult task. PMID- 1619073 TI - Topical corticosteroids and Staphylococcus aureus in atopic dermatitis. AB - BACKGROUND: Atopic dermatitis is commonly colonized with Staphylococcus aureus in high densities. OBJECTIVE: Our purpose was to study the effect of topical corticosteroids on the colonization of S. aureus in atopic dermatitis. METHODS: Sixty-six patients were treated with moderately potent, or very potent corticosteroids. Quantification of S. aureus and evaluation of the severity of the eczema was performed before, after 1 week, and after 2 weeks of treatment. RESULTS: Fifty-three patients carried S. aureus in the most pronounced lesion before treatment. The colonization was significantly correlated with the severity of the eczema. The density of S. aureus was reduced by topical corticosteroids. The reduction increased with the potency of the corticosteroid and was most pronounced during the first week. S. aureus was eliminated after a successful 2 week treatment with a very potent corticosteroid. Propylene glycol 25% added to a moderately potent corticosteroid did not significantly increase the reduction of S. aureus. CONCLUSION: Topical corticosteroids of sufficient potency reduce the density of S. aureus in atopic dermatitis. PMID- 1619074 TI - Failure of Borrelia burgdorferi to survive in the skin of patients with antibiotic-treated Lyme disease. AB - BACKGROUND: Borrelia burgdorferi has been cultivated from clinically normal skin (previous erythema migrans sites) after antibiotic therapy for Lyme disease. OBJECTIVE: We investigated the possibility of similar findings in 13 of our patients with antibiotic-treated Lyme disease from whom B. burgdorferi was cultivated from their erythema migrans lesions before antibiotic therapy. METHODS: After treatment with doxycycline or a combination of amoxicillin and probenecid, skin biopsy specimens were obtained from clinically normal skin adjacent to the previous biopsy sites and cultured. RESULTS: B. burgdorferi was not cultivated from these posttreatment biopsy sites. CONCLUSION: The failure of B. burgdorferi to survive in the former erythema migrans sites of our antibiotic treated patients, as well as their favorable clinical response, supports the use of doxycycline or combined amoxicillin and probenecid in the treatment of early Lyme disease but does not preclude the survival of the organism in other tissues. PMID- 1619076 TI - Diagnostic utility of magnetic resonance imaging in malignant melanoma. AB - BACKGROUND: Dermatologists sometimes have difficulty in making the diagnosis of a melanocytic tumor. OBJECTIVE: Our purpose was to establish a noninvasive method for the diagnosis of malignant melanoma. We investigated the diagnostic usefulness of magnetic resonance imaging (MRI) in 23 lesions of primary malignant melanoma, metastatic malignant melanoma, and benign pigmented skin tumors. METHODS: The morphologic characteristics and the signal intensity of the tumors were analyzed to differentiate malignant and benign pigmented skin tumors by means of the tumor-to-fat contrast ratio of the signal intensity. RESULTS: The morphologic characteristics of the tumors obtained by MRI were not an absolute criterion for diagnosis of malignant melanoma, but the signal intensity of the tumor assessed by the tumor-to-fat contrast ratio on T2-weighted images clearly differentiated between primary malignant melanoma and benign pigmented skin tumors. CONCLUSION: These findings indicated that MRI is useful for noninvasive diagnosis of malignant melanoma. PMID- 1619075 TI - Darier-White disease: a review of the clinical features in 163 patients. AB - BACKGROUND: Darier's disease is a rare, dominantly inherited genodermatosis; there have not been any large clinical studies of patients with this disease. OBJECTIVE: Our purpose was to document the clinical features in a large group of patients with Darier's disease. METHODS: Data were collected from 163 affected persons. RESULTS: The onset usually occurred between the ages of 6 and 20 years. The disease has a predilection for the skin in seborrheic areas; 96% had acral signs; 6% had hypertrophic flexural involvement; and 13% had oral mucosal lesions. There was no remission. Topical therapy sometimes provided relief of symptoms but had no effect on the progress of the disease. Oral retinoids were effective, but long-term therapy was tolerated poorly. Most patients did not have other medical problems. CONCLUSION: Although Darier's disease is a chronic and unremitting burden, most patients manage to lead a relatively normal life. PMID- 1619077 TI - Eosinophilic pustulosis of the scalp in childhood. AB - BACKGROUND: Among sterile pustulosis in childhood, a pruritic relapsing eosinophilic variant beginning in infancy and located mostly in the scalp was first described as eosinophilic pustular folliculitis in infancy by Lucky and colleagues in 1984. OBJECTIVE: Our purpose is to describe such a condition in five boys and one girl and comment on differential diagnosis and relation with Ofuji's disease. METHOD: This is a clinicopathologic study. RESULTS: All patients had scalp pustules beginning in infancy or early childhood that were unresponsive to antibiotic therapy. Lesions also occurred on other areas but the scalp was the major site of involvement. Although secondary infection was demonstrated in one case, the lesions were primarily sterile. Smears of pustules showed a variable proportion of eosinophils. Histopathologic findings suggested a major role for eosinophils in this disorder because dermal eosinophilia was noted in all patients. The inflammatory pattern was not similar to Ofuji's disease. Transient blood eosinophilia was recorded in five patients. Topical steroids relieved inflammatory episodes. Dapsone was tried in one case with apparent benefit. CONCLUSION: Eosinophilic pustulosis of the scalp in childhood is a self-limited disease that can be relieved by topical steroids. PMID- 1619078 TI - Treatment of adult Langerhans cell histiocytosis with etoposide. AB - BACKGROUND: Langerhans cell histiocytosis (LCH) is a reactive disease in which abnormal Langerhans cells accumulate in various body sites and cause damage to affected organs. Adults often do not respond to conventional therapy with local or systemic steroids. OBJECTIVE: Our purpose was to investigate intravenous etoposide as monotherapy in the treatment of adult patients with severe or resistant LCH. METHODS: In an open study, three adult patients with LCH (one with single-system skin disease and two with multisystem disease) were treated with etoposide, 100 mg/m2/day, for 3 days. This was repeated every 3 or 4 weeks for three or four cycles. RESULTS: All patients achieved clinical remission that persisted during a 12- to 14-month follow-up. No serious side effects were noted. CONCLUSION: We recommend the use of etoposide monotherapy in severe or restricted LCH in adults. PMID- 1619079 TI - Treatment of aggressive basal cell carcinoma with intralesional interferon: evaluation of efficacy by Mohs surgery. AB - BACKGROUND: Intralesional interferon has shown activity in the treatment of noduloulcerative and superficial basal cell carcinomas (BCC). OBJECTIVE: Our purpose was to study the efficacy of intralesional interferon in the treatment of aggressive BCCs. METHODS: Fifteen patients with histologically proven primary morpheaform or recurrent BCCs were referred for Mohs surgery. They received nine intralesional injections of 1.5 million IU of interferon alfa-2b three times a week for 3 weeks (total dose 13.5 million IU). All tumors were located on the face and measured 7 to 25 mm in diameter. RESULTS: In four patients (27%) no residual tumor was found at surgery. In five (33%) tumor size was reduced by 75%. The remaining six patients (40%) showed no response to intralesional interferon. CONCLUSION: At the dosage used, interferon was able to cure only a minority of aggressive BCCs. PMID- 1619080 TI - The reliability of a second biopsy for determining residual tumor. AB - BACKGROUND: Often after biopsy a skin cancer appears to resolve clinically and a repeat biopsy may be done on the area in question before proceeding with further treatment. OBJECTIVE: Our purpose was to assess the value of a subsequent biopsy in the treatment of skin cancers previously diagnosed by biopsy results. METHODS: The results of a subsequent biopsy were compared with the results of Mohs micrographic surgery in 291 patients with biopsy-established basal cell carcinoma and squamous cell carcinoma. Pre-Mohs surgery curettings were examined in 60 of these patients to evaluate whether these could have caused false-negative Mohs results. RESULTS: One hundred nineteen patients had a negative second biopsy, of which 75 (63%) had residual tumor at surgery. Eight of 60 patients in whom the curettings were examined had negative results from both biopsy and Mohs surgery; tumor in the curettings was shown in six of these eight patients (75%). CONCLUSION: This study suggests that 63% or more of subsequent biopsy specimens for skin cancer may yield false-negative results and casts doubt on the usefulness of a subsequent biopsy before surgery. PMID- 1619081 TI - Immunofluorescence on split skin for the detection and differentiation of basement membrane zone autoantibodies. AB - The autoimmune subepidermal bullous diseases are characterized by autoantibodies to the basement membrane zone of stratified squamous epithelium. Recent studies have shown that the antibodies have characteristic ultrastructural and antigenic binding properties and that differentiating between those properties can be useful in distinguishing one disease from another. Immunofluorescence microscopy is widely used to detect basement membrane zone autoantibodies. The test has traditionally used tissue substrates with an intact basement membrane zone. Those substrates are limited because autoantibody binding cannot always be detected and because autoantibodies with different ultrastructural and antigenic binding properties cannot be distinguished from each other. Normal human skin that has been separated through the basement membrane zone (i.e., split skin) has recently been used as a substrate for detecting and characterizing basement membrane zone autoantibodies by immunofluorescence. Studies indicate that split skin is a more sensitive substrate than intact skin for detecting the antibodies and that antibodies with different ultrastructural binding sites can often be differentiated from one another on split skin. Those studies suggest split skin is the substrate of choice for the routine immunofluorescence evaluation of autoimmune subepidermal bullous diseases. PMID- 1619082 TI - Topical glucocorticoids with improved benefit/risk ratio: do they exist? AB - Topical glucocorticoids are still among the dermatologicals most frequently used. This is due to their undebatable potency in inflammatory skin disease. Their use is limited by the fear of side effects both systemic and topical, especially skin atrophy. Hence, congeners with an increased benefit-risk ratio are urgently needed and research on new drugs no longer focuses on more active drugs but safer ones. Only recently, evidence has been forwarded that the goal is realistic. Some new glucocorticoids, especially the nonfluorinated double-ester type such as prednicarbate, appear promising. In fact, they seem to affect fibroblast growth in vitro as well as skin thickness in vivo less than equipotent conventional glucocorticoids. Pertinent findings in humans have been obtained with the use of ultrasound equipment. The relevant aspects of chemistry, pharmacology, clinical benefits, and toxicology of the various glucocorticoids old and new are reviewed, as are potential future alternatives. PMID- 1619083 TI - The spectrum of nail disease in patients with human immunodeficiency virus infection. AB - There are no known pathognomonic nail signs of human immunodeficiency virus (HIV) infection. However, several presentations should increase the index of suspicion. (1) Proximal white subungual onychomycosis or superficial white onychomycosis, especially of the fingernails, is present. Trichophyton rubrum appears to cause both most commonly in HIV-infected patients. Periungual dermatophyte involvement and involvement of all 10 fingernails is unusual in non-HIV-infected persons. (2) Candida is a primary pathogen of the nail bed and nail plate especially if many nails are involved. (3) A destructive, almost granulomatous-like psoriatic involvement of the nails is present. (4) Squamous cell carcinoma of the nail bed in a young adult. There are no clinical trails to confirm the efficacy of therapy mentioned in this article. The treatment suggestions are empirical and are the personal views of the authors. PMID- 1619084 TI - Psoriasis. I. Pathogenesis. PMID- 1619085 TI - A comparison of the diagnoses of a graphologist with results of psychological tests. 1941. AB - A class of twenty-four students who had previously been given intelligence, interest, and personality tests wrote to a newspaper graphologist for vocational guidance, their university connection being disguised and the requests being staggered over a period of more than one week. The vocational recommendations and the diagnoses of personality traits were then compared with the test scores. It was found that: 1. Assuming that a certain minimum intelligence is necessary for a given occupation, the occupations recommended by the graphologist showed no more than a change relationship with the recommendations which a psychologist would have made on the basis of intelligence tests. 2. Assuming that a certain pattern of interests is desirable for adjustment in an occupation, the occupation recommended by the graphologist were quite different from those which a psychologist would have recommended on the basis of an interest inventory, certain unsuitable occupations being recommended with more than chance frequency by the graphologist. 3. The graphologist's estimates of the students' personality traits showed no more than a chance agreement with those made by a psychologist on the basis of personality inventories in the case of four traits, and in the case of the two others were worse than change, again revealing a constant error. 4. There was reason for ascribing these constant errors to a belief in the existence of opportunities in certain areas rather than to poor diagnosis alone, and to the use of clues to personality traits not intrinsic in handwriting. 5. It was pointed out that, with certain graphological principles gaining acceptance in scientific circles, it is still important to check the activities of persons who claim to use these newer principles. PMID- 1619086 TI - Introduction to the special section on the emotional concomitants of brain damage. AB - The purpose of this introduction is to emphasize the theoretical and clinical implications of studying emotion after brain damage. Theoretically, it is one way of elucidating critical neural substrates of emotion and the interaction of cognitive and noncognitive determinants. Clinically, the cognitive and other behavioral changes associated with certain types of brain damage may make traditional methods of assessing emotion inaccurate. This special section is designed to review current knowledge regarding these issues and to emphasize their theoretical and clinical importance. PMID- 1619087 TI - Neural mechanisms of emotion. AB - When viewed from an evolutionary perspective, the neural mechanisms of emotion can be seen to be distributed across the brainstem, limbic, paralimbic, and neocortical regions. Descending and ascending connections among these levels are discussed in relation to three types of emotional processes: peripheral effects on patterned bodily responses, central effects on cognitive processing, and subjective emotional experience. Descending influences from the higher to the lower levels allow for an increasing coordination and flexibility of emotional responses, culminating in patterned activity across the peripheral endocrine, autonomic, and motor systems. Ascending influences from lower to higher levels provide preparatory modulation of cortical pathways, thus enabling perceptual and cognitive processing that is adaptive given the current emotional state. The bodily feelings of emotion are a function of cortical interoceptive sensory fields, activated by centrally generated signals or peripheral inputs from the body. PMID- 1619088 TI - Interhemispheric and intrahemispheric control of emotion: a focus on unilateral brain damage. AB - Neocortical contributions to emotional processing are discussed. First, parameters critical to the neuropsychological study of emotion are examined: interhemispheric (right, left) and intrahemispheric (anterior, posterior) factors, processing mode (expression, perception), and communication channel (facial, prosodic, lexical). Second, neuropsychological theories of emotion are described: right-hemisphere and valence hypotheses. Third, experimental studies of right-brain-damaged, left-brain-damaged, and normal adults are reviewed, on the basis of mode and channel, with a focus on stroke. Findings support right cerebral hemispheric dominance for emotion, regardless of valence and channel, and are more consistent for perception than expression. When lesion site is a factor, posterior sites are important for perception and anterior ones for expression. Finally, clinical implications are suggested for aphasia rehabilitation and for assessment of affect in neurological disorders. PMID- 1619089 TI - "No longer Gage": frontal lobe dysfunction and emotional changes. AB - This review presents the multiple changes in emotional response and personality that occur after damage to the frontal systems, proposes operational definitions, and analyzes the published reports according to these definitions. Neurological causes of frontal lobe damage and associations of frontal dysfunction with psychiatric disturbances are summarized. It is concluded that symptoms of frontal lobe damage that have been labeled as emotional disturbances may be classified as disorders of drive or motivation, mood (subjective emotional experience), and affect (emotional expression). It is proposed that the primary change after frontal lobe pathology is a disorder of personality, a change in the stable response patterns that define an individual as a unique self. Dysfunction of personality includes cognitive abilities, with a disorder of self-reflective awareness as a key deficit. PMID- 1619090 TI - Personality disturbances associated with traumatic brain injury. AB - Personality disturbances associated with traumatic brain injury are reviewed. The varied structural pathology of the brain in this patient group makes it difficult to specify how different brain lesions may result in specific emotional and motivational disturbances. However, an attempt to clarify terms and review empirical findings is made. Longitudinal prospective studies that utilize appropriate control groups are needed. Future research may especially benefit by considering the long-term effects of early agitation following traumatic brain injury as well as the problem of aspontaneity and impairment of self-awareness. PMID- 1619091 TI - Emotional changes with multiple sclerosis and Parkinson's disease. AB - Multiple sclerosis (MS) and Parkinson's disease (PD) are relatively common neurological disorders. Both disorders are chronic and progressive, produce varying degrees of physical disability, and result in characteristic neuropathological changes to a variety of subcortical brain structures. Patients with MS or PD also exhibit a higher prevalence of emotional disorders relative to other patient groups with comparable degrees of physical disability. The present review (a) examines specific methodological issues associated with research in this area, (b) describes the range and severity of emotional disorders in MS and PD, and (c) examines both endogenous and reactive explanations to account for the increased prevalence of emotional dysfunction in these two disorders. Suggestions for future research are offered, as well as implications for treatment. PMID- 1619092 TI - Alzheimer's disease and depression. AB - This article reviews the empirical literature available on the phenomenon of depression in Alzheimer's disease (AD). Although not extensively studied, there is accumulating evidence to suggest that depression affects a large number of patients with AD and can have profound effects on both the long-term functioning of these patients and the well-being of their caregivers. Thus far, the field is dominated by studies of prevalence. Considerably rarer are studies investigating etiology, association with other aspects of disease, impact on patients and caregivers, assessment, and treatment. The conceptual issues, methodological differences, and implications of the studies that exist thus far are discussed. PMID- 1619093 TI - Biological markers, treatment outcome, and 1-year follow-up in endogenous depression: electroencephalographic sleep studies and response to cognitive therapy. AB - Although there are now considerable data attesting to the efficacy of several forms of treatment for depression, there is surprisingly little information to guide the selection of the treatment most likely to benefit a given patient. Biologic markers of depression have received much attention for their potential to provide theoretically and clinically meaningful subgroups for specific treatments. The relationship between electroencephalographic (EEG) sleep disturbances, treatment outcome, and 1-year follow-up was examined for a sample of 53 patients with endogenous major depression receiving cognitive-behavioral therapy. Overall, there was little support for the prediction of a difference in short- or long-term outcome between patients with and without EEG sleep disturbances. PMID- 1619094 TI - Clinically significant change: Jacobson and Truax (1991) revisited. AB - The relationship between statistically and clinically significant change has been enigmatic. Jacobson and Truax (1991) have proposed an important step toward rapprochement. However, their suggested index of clinically significant change neglects possible confounding of improvement rate estimates by regression to the mean. An alternative method is described that incorporates an adjustment that minimizes this confounding when statistical regression has been shown to be present. If regression is not present, the Jacobson and Truax method is more appropriate; if regression is present, the Edwards-Nunnally method (Edwards, Yarvis, Mueller, Zingale, & Wagman, 1978) is more appropriate. The two methods are compared, and the effects of instrument reliability and sample deviance on estimated improvement rates are demonstrated using general well-being test-retest data from a sample of older adult mental health outpatients. PMID- 1619095 TI - Epidemiology of trauma: frequency and impact of different potentially traumatic events on different demographic groups. AB - The frequency and impact of 10 potentially traumatic events were examined in a sample of 1,000 adults. Drawn from four southeastern cities, the sample was half Black, half White, half male, half female, and evenly divided among younger, middle-aged, and older adults. Over their lifetimes, 69% of the sample experienced at least one of the events, as did 21% in the past year alone. The 10 events varied in importance, with tragic death occurring most often, sexual assault yielding the highest rate of posttraumatic stress disorder (PTSD), and motor vehicle crash presenting the most adverse combination of frequency and impact. Numerous differences were observed in the epidemiology of these events across demographic groups. Lifetime exposure was higher among Whites and men than among Blacks and women; past-year exposure was highest among younger adults. When impact was analyzed as a continuous variable (perceived stress), Black men appeared to be most vulnerable to the effects of events, but young people showed the highest rates of PTSD. PMID- 1619096 TI - Cognitive-behavioral intervention with aggressive boys: three-year follow-up and preventive effects. AB - This study examined the longer term preventive effects of a school-based intervention with boys referred by classroom teachers as highly aggressive and disruptive. Three years after intervention, boys who had received an anger coping (AC) program were compared with a group of untreated boys. The AC boys had lower rates of drug and alcohol involvement and had higher levels of self-esteem and social problem-solving skills. The AC boys were not significantly different from previously nonaggressive boys on these variables at follow-up. Although the overall intervention did not have longer term effects on delinquency rates or classroom behavior, a subset of boys who also received booster sessions did display maintenance of certain classroom behavior improvement. Implications for intensification of cognitive-behavioral interventions are discussed. PMID- 1619097 TI - Stress, coping, and psychological adjustment of adults with sickle cell disease. AB - A transactional model of psychological adjustment to chronic illness was examined with 109 African-American adults with sickle cell disease (SCD). Good psychological adjustment was associated with lower levels of perceived daily stress and stress regarding SCD illness tasks, higher efficacy expectations, less use of palliative coping methods, less use of negative thinking/passive adherence pain-coping strategies, and family functioning characterized by high levels of support and low levels of conflict and control. Overall the underlying stress and coping conceptual model accounted for 44-50% of the variance in psychological adjustment. PMID- 1619098 TI - Therapeutic empathy and recovery from depression in cognitive-behavioral therapy: a structural equation model. AB - This study demonstrated that therapeutic empathy has a moderate-to-large causal effect on recovery from depression in a group of 185 patients treated with cognitive-behavioral therapy (CBT). The authors simultaneously estimated the reciprocal effect of depression severity on therapeutic empathy and found that this effect was quite small. In addition, homework compliance had a separate effect on clinical recovery, over and above the effect of therapeutic empathy. The patients of novice therapists improved significantly less than did the patients of more experienced therapists, when controlling for therapeutic empathy and homework compliance. Ss who terminated therapy prematurely were less likely to complete the self-help assignments between sessions, rated their therapists as significantly less empathic, and improved significantly less. Ss with borderline personality disorder improved significantly less, but they rated their therapists as just as empathic and caring as other patients. The significance of these findings for psychotherapy research, treatment, and clinical training is discussed. PMID- 1619099 TI - A comparison of three family therapy programs for treating family conflicts in adolescents with attention-deficit hyperactivity disorder. AB - Sixty-one 12- to 18-year-olds were randomized to 8-10 sessions of behavior management training (n = 20), problem-solving and communication training (n = 21), or structural family therapy (n = 20). Families were assessed at pre- and posttreatment and 3-month follow-up. All treatments resulted in significant reductions in negative communication, conflicts, and anger during conflicts and improved ratings of school adjustment, reduced internalizing and externalizing symptoms, and decreased maternal depressive symptoms. Most outcomes remained stable between posttreatment and follow-up, and some continued to improve over this time. Despite group improvements, analyses of clinically significant change and clinical recovery within Ss showed that only 5-30% reliably improved from treatment and only 5-20% recovered following treatment. The three treatments did not differ in these rates. PMID- 1619100 TI - Social support, AIDS-related symptoms, and depression among gay men. AB - This study examined the impact of social support and HIV-related conditions on depression among 508 gay men participating in the San Francisco Men's Health Study, a population-based prospective study of single men aged 25-54 years. The number of HIV-related symptoms experienced significantly predicted depression cross-sectionally and 1 year later. Satisfaction with each of three types of social support (emotional, practical, informational) was inversely correlated with depression. Men who were more satisfied with the social support they received were less likely to show increased depression 1 year later. Degree of satisfaction with informational support appeared especially critical in buffering the stress associated with experiencing HIV symptoms. These findings offer valuable insight in understanding the psychological needs of gay men confronting the AIDS crisis and have important practical implications for designing mental health services to meet those needs. PMID- 1619101 TI - Attributions and relapse in opiate addicts. AB - This study investigated whether attributions of opiate addicts would predict both their ability to abstain from future use and their reactions to abstinence violations. Measures of generalized beliefs about responsibility for positive and negative outcomes and specific attributions about relapse episodes were elicited from 80 addicts at the time of admission for inpatient detoxification and treatment. Addicts who at admission attributed to themselves greater responsibility for negative outcomes and who attributed relapse episodes to more personally controllable factors were subsequently (at 6-month follow-up) more likely either to be completely abstinent or to contain the effects of temporary lapses into opiate use. PMID- 1619102 TI - Psychological and social indicators of suicide ideation and suicide attempts in Zuni adolescents. AB - Suicide behavior is a significant problem for many American Indian populations, often more so than in the general population, but little tribal-specific data available. In this study, baseline data on the correlates of suicide ideation and the social and psychological differences between suicide attempters and nonattempters were collected on a sample of 84 Zuni adolescents. Results show significant correlations between a measure of suicide ideation and past suicide attempt behavior, drug use, depression, hopelessness, stress, psychological symptomatology, social support, liking for school, and interpersonal communication. Significant differences between the 30% of the students who reported having previously attempted suicide and the nonattempters were also found on these measures. Areas for education and prevention efforts are suggested. PMID- 1619103 TI - Deterioration of intellect among children surviving leukemia: IQ test changes modify estimates of treatment toxicity. AB - This study assessed the association of young age at treatment, cranial irradiation, and time since treatment with intellectual deterioration among 49 long-term survivors of childhood leukemia. Ss had been randomized to receive low dose cranial radiation therapy or high-dose chemotherapy. Longitudinal assessments of intellect were conducted. No significant effects of treatment group or age at treatment were detected. A small but statistically significant decline in mean full-scale IQ was noted over time (M = -3.6). Reanalysis with IQ test version included as a covariate eliminated IQ declines found initially. Results suggest (a) that there has been reduced toxicity of these methods of treatment and (b) that the magnitude and direction of error introduced by changing tests may approximate the magnitude of adverse effects on IQ from treatment. PMID- 1619104 TI - Control of the straw itch mite (Acari: Pyemotidae) with sulfur in an insect rearing facility. AB - The ectoparasitic mite Pyemotes tritici (Lagreze-Fossat & Montane) (Acari: Pyemotidae) caused paralysis and reduced longevity in eucalyptus longhorned borer, Phoracantha semipunctata F., under laboratory rearing conditions. Application of dusting sulfur to logs that contained pupating borers greatly reduced densities of mites on emerging adult beetles and increased beetle survivorship. Uniform application to all logs in a glasshouse effectively eradicated the mite infestation. A bioassay showed that sulfur may physically impede the dispersal of immature mites by adhering to the cuticle, but sulfur vapor did not act as a toxin. PMID- 1619105 TI - Differential development and reproduction of the German cockroach (Dictyoptera: Blattellidae) on three laboratory diets. AB - Development of nymphs and oocyte maturation in adults were examined in Blattella germanica (L.) reared on three commercial diets. Nymphs fed rat food developed significantly faster than nymphs fed two commercial dog foods. Similarly, oocytes matured more quickly in adult females that were raised on rat food than in females raised on dog food. Nymphal development and oocyte maturation were slower in insects that were fed whole dog food pellets than in insects fed ground dog food, suggesting that grinding the diet diminishes a mechanical barrier in whole dog food pellets. Comparisons of processed canine food and unprocessed canine food indicated that diets were significantly inferior after the steam extrusion process. Rat food is normally not subjected to such conditions and both processed and unprocessed rat food are equally suitable for B. germanica. The significance and implications for comparative studies with cockroaches are discussed. PMID- 1619106 TI - Simple in-vitro feeding system for northern fowl mites (Acari: Macronyssidae). AB - The use of Parafilm membranes for in-vitro feeding of northern fowl mites, Ornithonyssus sylviarum (Canestrini & Fanzago), is described. A membrane stretched in two perpendicular directions, folded, heat-sealed, inflated, and twisted at the ends to form a sphere allowed a high percentage (greater than 80%) of surviving adult female mites to feed on whole chicken blood. A high percentage (7 of 10) of protonymphs also fed through the membrane. Mites were able to feed from the same sac for 3 d and oviposited on the sac. This technology has potential applications for use in rearing O. sylviarum and other hematophagous arthropods, and for physiological experimentation. PMID- 1619107 TI - Effects of permethrin on aquatic organisms in a freshwater stream in south central Alaska. AB - Permethrin (0.5%) was applied to individual Lutz spruce, Picea x lutzii Little, to protect them from attack by spruce beetles, Dendroctonus rufipennis (Kirby). Residue levels were monitored in a freshwater stream above, adjacent to, and below the treatment site at intervals before, during, and after treatment. Maximum residue levels in the stream within the treatment site ranged from 0.05 +/- 0.01 ppb 5 h after treatment to 0.14 +/- 0.03 ppb 8-11 h after treatment, with a decrease to 0.02 +/- 0.01 ppb 14 h after treatment. Levels of permethrin in standing pools near the stream within the treatment site were 0.01 +/- 0.01 ppb. Numbers of drifting aquatic invertebrates increased 2-fold during treatment and 4-fold 3 h after treatment and declined to before spray numbers within 9 h. Terrestrial insects did not appear to respond to treatments because none was found in stream drift samples. Trout fry (Dolly Varden), aquatic insect larvae, and periphyton (attached algae) within and below the treatment site during and after treatment did not show signs of mortality compared with an upstream untreated control site. PMID- 1619108 TI - Field worker exposure to selected insecticides applied to corn via center-pivot irrigation. AB - Field workers were monitored for dermal and respiratory exposure to chlorpyrifos (with and without crop oil), carbaryl, and permethrin at reentry intervals of 2, 4, 8, 24, and 48 h after application. Insecticides were applied to R3 stage corn through an overhead center-pivot irrigation system. Dermal exposure was measured by analyzing 18 gauze pads attached to the clothing of workers to represent human body regions. Hand exposure was determined using cotton gloves. Respiratory exposure was determined using portable air samplers equipped with polyurethane foam plugs to trap ambient insecticide residues. Gas liquid chromatography was used to quantify residues of chlorpyrifos and permethrin in gauze pads, gloves, and foam plugs. Carbaryl residues in pads, gloves, and foam plugs were analyzed using high-performance liquid chromatography. Highest dermal and respiratory exposures were found at the 2-h reentry interval. Exposures decreased as reentry interval increased. Dermal exposure was primarily confined to the hands. Residues detected by air samplers ranged from 0 to 0.03 micrograms/liter. Based on the estimated percentages of acute toxic dose (all less than 0.00038%), the risk of acute toxicity to workers at the intervals studied was low. PMID- 1619109 TI - Basal cell carcinoma arising on the ear of a young adult. PMID- 1619110 TI - Detection of selenium in generalized and localized argyria: report of four cases with X-ray microanalysis. AB - Electron microscopic and X-ray microanalytic studies were performed on four cases of argyria; one generalized and three localized. Deposition of electron dense granules was predominantly found on elastic fibers and around basal laminas of secretory portions of eccrine glands, although the amount of deposition was much less in the case of generalized argyria. In all four cases, X-ray microanalysis revealed that the depositions consisted mainly of silver, selenium, and sulfur. The importance of selenium in the detoxification of heavy metals was discussed. PMID- 1619111 TI - Significance of monocytosis in varicella and herpes zoster. AB - Percent ratios and absolute numbers of peripheral blood monocytes in patients with varicella and herpes zoster were determined and compared with those in patients with herpes simplex virus infection, measles and rubella. Monocytosis during the acute stage (p less than 0.01) was statistically significant in varicella and generalized and localized herpes zoster, compared with the levels in herpes simplex virus infection, measles and rubella. Absolute monocyte counts in varicella and HZ were significantly increased (p less than 0.02) beyond those of measles and rubella. The high % ratios of monocytes in varicella and herpes zoster during the acute stage decreased to normal ranges with cure. PMID- 1619112 TI - On multidimensional ultrasonic scattering in an inhomogeneous elastic background. AB - This work is concerned with the modeling of elastic wave scattering by solid or fluid-filled objects embedded in an inhomogeneous elastic background. The medium is probed by a monochromatic force and the scattered field is computed (forward problem) or observed (inverse problem) at some known receiver locations. Based on vector integral equations for elastic scattering, a general framework is developed, independent of both the problem geometry and the transmitter-receiver characteristics. This framework encompasses both forward and inverse modeling. In the forward model, a Born approximation for an inhomogeneous background is applied to obtain a closed form expression for the scattered field. In the inverse model, this approximation is also invoked to linearize for the multiparameter characteristic of the object. Finally, an iterative inversion scheme alternating forward and inverse modeling is proposed to improve the resolution and accuracy of the reconstruction algorithm. PMID- 1619113 TI - Annoyance caused by simultaneous impulse, road-traffic, and aircraft sounds: a quantitative model. AB - In this study, total annoyance caused by different simultaneous environmental sounds is investigated. In spite of a number of puzzling data in the literature, it is fairly well established that in combinations in which the annoyance of one source is considerably higher than that of another source, total annoyance is equal to the maximum annoyance of the separate sources. For combinations in which both sounds are about equally annoying, total annoyance seems to be higher than the maximum source-specific annoyance. The available data, however, are too rough to model total annoyance in these conditions. The present laboratory studies were therefore designed to explore further possible procedures to quantify total annoyance. Subjects rated the (total) annoyance caused by various combinations of impulse, road-traffic, and aircraft sounds. The results support a simple model which predicts the overall or total rating sound level L(t) for combinations of several types of sounds. Here, L(t) is numerically equal to the A-weighted equivalent sound level L(eq) of road-traffic sound with the same annoyance as caused by the combination of sounds. In the model, the sound exposure caused by the impulse and/or aircraft sounds is first expressed in the L(eq) of equally annoying road-traffic sound. With the help of source-specific dose-effect relationships, this is achieved by adding level-dependent penalties to the L(eq) of the respective sources. Weighted summation of the corrected L(eq)'s of the various sources then results in L(t). An optimal overall fit of the data from two separate experiments was obtained when the weighted summation of the corrected L(eq)'s was performed with the parameter k in k log(sigma 10(corrected L(eq) of source j)/k) set to 15. The standard deviation of the differences between the experimental results and the model predictions with k = 15 was equivalent to the small change in annoyance produced by a 1.5-dB shift in the L(eq) of road-traffic sound. Adoption of k = 15 implies that after correction, two equal L(eq)'s yield a total rating sound level which is 4.5 dB higher than each single-source corrected L(eq). PMID- 1619114 TI - A new portable sound processor for the University of Melbourne/Nucleus Limited multielectrode cochlear implant. AB - A new processor, called the spectral maxima sound processor (SMSP), has been developed for the University of Melbourne/Nucleus Limited multielectrode cochlear implant. The SMSP analyses sound signals by means of a bandpass filterbank having 16 channels which are allocated tonotopically to the implanted electrodes. Every 4 ms, typically, the six channels with the largest amplitudes are selected, and six corresponding electrodes are activated. In an ongoing study the performance of the SMSP is being compared with that of the Mini Speech Processor (MSP). Some results of speech perception tests from the first two SMSP users are presented, in which scores for the recognition of vowels, consonants, and words all showed significant increases over the corresponding MSP scores. PMID- 1619115 TI - Grouping in pitch perception: effects of onset asynchrony and ear of presentation of a mistuned component. AB - Three experiments investigated how the onset asynchrony and ear of presentation of a single mistuned frequency component influence its contribution to the pitch of an otherwise harmonic complex tone. Subjects matched the pitch of the target complex by adjusting the pitch of a second similar but strictly periodic complex tone. When the mistuned component (the 4th harmonic of a 155 Hz fundamental) started 160 ms or more before the remaining harmonics but stopped simultaneously with them, it made a reduced contribution to the pitch of the complex. It made no contribution if it started more than 300 ms before. Pitch shifts and their reduction with onset time were larger for short (90 ms) sounds than for long (410 ms). Pitch shifts were slightly larger when the mistuned component was presented to the same ear as the remaining 11 in-tune harmonics than to the opposite ear. Adding a "captor" complex tone with a fundamental of 200 Hz and a missing 3rd harmonic to the contralateral ear did not augment the effect of onset time, even though the captor was synchronous with the mistuned harmonic, the mistuned component was equal in frequency to the missing 3rd harmonic of the captor complex tone and it was played to the same ear as the captor. The results show that a difference in onset time can prevent a resolved frequency component from contributing to the pitch of a complex tone even though it is present throughout that complex tone. PMID- 1619116 TI - Informational processing of complex sound. III: interference. AB - In this study, theoretical results from information theory and detection theory are applied to provide a formal analysis of the interaction of target and context uncertainty on the discrimination of brief multitone sequences. The experiments employ a sample-discrimination task in which the performance of an ideal observer is held constant while the relative variability of the target sigmaT and context sigmaC is varied. Listener performance in these experiments was less than ideal but increased monotonically with sigmaT/sigmaC whether the task was to discriminate the frequency or the intensity of the target. Performance was also constant for a constant sigmaT/sigmaC regardless of the target's position in the sequence. The results are consistent with a class of models in which the decision variable is a weighted sum of the tone values comprising the sequence. Weighting functions computed from the trial-by-trial date suggest that limits in performance result from trial-by-trial variability in the weights. The decision variable also serves as the basis for an analysis in which performance is linearly related to the information rate of the context independent of target position or task. In this analysis, target and context uncertainty contribute additively to the overall uncertainty associated with the decision variable. PMID- 1619117 TI - Evaluation of a method of simulating reduced frequency selectivity. AB - The accuracy of a method of simulating reduced frequency selectivity by the spectral smearing of complex stimuli has been evaluated. First an excitation pattern that would be evoked by a given nonsmeared stimulus in an impaired ear with broad auditory filters was estimated. Then the spectral smearing of the stimulus that would be necessary to create the same excitation pattern in a normal ear was calculated. The smearing was based on the shapes of simulated broad auditory filters; both symmetric and asymmetric broad filters were simulated. The method was used to process notched noise, and tones in notched noise, and the processed stimuli were used in a series of experiments with normally hearing subjects measuring the threshold for the tone in notched noise. The resulting data were used to derive auditory filter shapes. The derived filter shapes were generally similar to the expected shapes (based on the type of spectral smearing used), but there were some systematic discrepancies and some individual differences. The discrepancies do not seem to be due to the use of information derived from phase locking, since they were observed both at 1 kHz (where phase locking occurs) and at 6 kHz (where phase locking probably does not occurs). The discrepancies also do not seem to be due to the transmission characteristics of the outer/middle ear, since they occurred both when these characteristics were taken into account in the fitting procedure, and when the stimuli were preshaped to compensate for these characteristics. The influence of the subjects' own auditory filters probably can explain some of the discrepancies; the excitation pattern evoked by the spectrally smeared stimuli can be significantly influenced by the subjects' own filters when those filters are not much sharper than the simulated filters used to produce the smeared stimuli. Finally, some of the discrepancies can probably be explained by subjects combining information across auditory filters, rather than just using the single 'best' filter in each condition; this represents a limitation of the fitting procedure rather than of the simulation itself. Overall, the simulation worked reasonably well, especially when the smearing was based on symmetric filters. PMID- 1619118 TI - The detectability of a tone added to narrow bands of equal-energy noise. AB - The ability to detect a 2000-Hz tone added to bands of noise centered at 2000 Hz was measured using a two-interval, forced-choice, pulsed-masker paradigm. The stimuli ranged in duration from 50-200 ms, and the maskers ranged in bandwidth from 5-320 Hz. In one condition, the bands of noise had equal energy across the two intervals of each trial and in a second condition the levels of the stimuli were independently and randomly chosen from a 30-dB range on a presentation-by presentation basis. The energy model failed to predict the data obtained either in the presence or in the absence of level variation. Control experiments showed that exposure to level variation yielded an overall reduction in sensitivity, suggesting that the presence of level variation leads to changes in the listeners' detection strategies. Computer simulations indicated that changes in either the fine structure or envelopes of the waveforms were sufficient to account for detection when changes in stimulus energy were not reliable. PMID- 1619120 TI - Accuracy of pitch matching for pure tones and for complex tones with overlapping or nonoverlapping harmonics. AB - The discrimination of the fundamental frequency (fo) of pairs of complex tones with no common harmonics is worse than the discrimination of fo for tones with all harmonics in common. These experiments were conducted to assess whether this effect is a result of pitch shifts between pairs of tones without common harmonics or whether it reflects influences of spectral differences (timbre) on the accuracy of pitch perception. In experiment 1, pitch matches were obtained between sounds drawn from the following types: (1) pure tones (P) with frequencies 100, 200, or 400 Hz; (2) a multiple-component complex tone, designated A, with harmonics 3, 4, 8, 9, 10, 14, 15, and fo = 100, 200, or 400 Hz; (3) A multiple-component complex tone, designated B, with harmonics 5, 6, 7, 11, 12, 13, 16, and with fo = 100, 200 or 400 Hz. The following matches were made; A vs A, B vs B, A vs P, B vs P and P vs P. Pitch shifts were found between the pure tones and the complex tones (A vs P and B vs P), but not between the A and B tones (A vs B). However, the variability of the A vs B matches was significantly greater than that of the A vs A or B vs B matches. Also, the variability of the A vs P and B vs P matches was greater than that for the A vs B matches. In a second experiment, frequency difference limens (DLCs) were measured for the A vs A, B vs B, and A vs B pairs of sounds. The DLCs were larger for the A vs B pair than for A vs A or B vs B. The results suggest that the poor frequency discrimination of tones with no common harmonics does not result from pitch shifts between the tones. Rather, it seems that spectral differences between tones interfere with judgements of their relative pitch. PMID- 1619119 TI - The role of envelope fluctuations in an apparent demonstration of suppression in simultaneous masking. AB - Fastl and Bechly [J. Acoust. Soc. Am. 74, 754-757 (1983)] reported that the threshold of a brief 900-Hz signal simultaneously masked by a band of noise. 100 Hz wide, centered at 1000 Hz, was reduced by approximately 8 dB by the addition of an 1150-Hz tone having a level of 20 dB above that of the narrow-band masker. They concluded that this decrease in threshold was a demonstration of suppression in simultaneous masking. Here it is argued that Fastl and Bechly's results simply reflect the poorer detectability of signals masked by higher-frequency fluctuating maskers (their narrow-band masker) than by relatively flat-envelope maskers (their composite narrow-band plus tonal masker). The results of three experiments support the masker-envelope explanation. In the first experiment, as in the report of Fastl and Bechly, the masker centered at 1000 Hz (M1) was a narrow-band noise and the masker centered at 1150 Hz (M2) was a tone. Fastl and Bechly's result was replicated. However, thresholds obtained when M1 was presented alone (the M1-only condition) were more affected by the starting level of the signal within each adaptive track than were thresholds obtained when M1 and M2 were presented together (the M1+M2 condition). This result paralleled a previous report that starting level influenced performance more with fluctuating than with flat-envelope maskers. For the four of seven subjects wh showed learning, there was also more improvement in the M1-only than in the M1 + M2 condition. In the second experiment, M1 was a tone and M2 was a narrow-band noise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619121 TI - Fringe effects in modulation masking. AB - Modulation detection thresholds (20 log ms) for a sinusoidally amplitude modulated (SAM) noise were measured in the presence of a SAM noise masker with a modulation depth (mm) of 1.0 and a modulation frequency of 16 or 64 Hz. The signal and masker carriers were presented continuously, and the signal was modulated during one of the two 500-ms observation intervals. The masker was modulated during both observation intervals and, in some conditions, for a certain amount of time before and after signal modulation. The duration of this "fringe" ranged from 62.5 ms to continuous (masker modulated throughout the thresholds estimate). The first experiment showed that a 500-ms fringe could reduce masked thresholds by 4-6 dB, but only at low signal modulation frequencies (2-8 Hz). In the second and third experiments, it was found that the fringe had to have a duration of 500 ms and a depth of about 0.75 to be maximally effective. A final, supplementary experiment indicated that the fringe effect is not due solely to the fringe that occurs prior to the observation intervals. The results are discussed in terms of both peripheral and central auditory processing. PMID- 1619122 TI - Differences in auditory performance between monaural and dichotic conditions. I: masking thresholds in frozen noise. AB - Thresholds of a 5-ms, 1-kHz signal were determined in the presence of a frozen noise masker. The noise had a flat power spectrum between 20 Hz and 5 kHz and was presented with a duration of 300 ms. The following interaural conditions were tested with four listeners: Noise and signal monaural at the same ear (monaural condition, NmSm), noise and signal identical at both ears (diotic condition, NoSo), noise identical at both ears and signal monaural (dichotic condition, NoSm) and uncorrelated noise at the two ears and signal monaural (NuSm). The signal was presented at a fixed temporal position with respect to the frozen noise in all measurements and thresholds were determined for different starting phases of the carrier frequency of the signal. Variation of the carrier phase strongly influenced the detection in the diotic condition and the masked thresholds varied by more than 10 dB. The pattern of thresholds for the monaural condition was less variable and the thresholds were generally higher than for the diotic condition. The monaural-diotic difference for specific starting phases amounted to as much as 8 dB. Comparison measurements using running noise maskers revealed no such difference. This relation between monaural and diotic thresholds was further investigated with eight additional subjects. Again, monaural and diotic thresholds in running noise were identical, while in frozen noise, diotic thresholds were consistently lower than monaural thresholds, even when the ear with the lower NmSm threshold was compared. For the starting phase showing the largest monaural-diotic difference, the thresholds for NoSm lay between the monaural and the diotic values. At other starting phases, the NoSm threshold was clearly lower than both the NmSm and the NoSo threshold. One possible explanation of the observed monaural-diotic differences relates to contralateral efferent interaction between the right and the left hearing pathway. A prediction based on this explanation was verified in a final experiment, where frozen-noise performance for NmSm was improved by simultaneously presenting an uncorrelated running noise to the opposite ear. PMID- 1619123 TI - Formant frequency estimates for abruptly changing area functions: a comparison between calculations and measurements. AB - Vocal tract area functions may contain quite abrupt changes in cross-sectional area. In formant frequency calculations for such area functions, an inner length correction (ILC) should be applied. The relevance of this correction was investigated by comparing acoustic measurements obtained from a physical model of the vocal tract with data gathered by means of computer simulations. Calculating formant frequencies without applying internal length corrections caused substantial errors, particularly for area functions representing apical stops just anterior to occlusion. Decentering and axial symmetry in the arrangement of the area elements of the physical model were briefly studied and found to have effects on the formant frequency values. PMID- 1619124 TI - Young cochlear implant users' response to delayed auditory feedback. AB - This investigation determined whether the signal provided by the Cochlear Corporation Nucleus cochlear implant can convey enough speech information to induce a response to delayed auditory feedback (DAF), and whether prelingually deafened children who received a cochlear implant relatively late in their speech development are susceptible. Ten children with the Nucleus cochlear implant spoke simple phrases, first without and then with DAF. Three prelingually deafened subjects and the only two postlingually deafened subjects demonstrated longer phrase durations when speaking with DAF than without it. Two of the prelingually deafened subjects who demonstrated a response received their cochlear implants at the age of 5 years. PMID- 1619125 TI - The use of static and dynamic vowel cues by multichannel cochlear implant users. AB - Multichannel cochlear implant users vary greatly in their word-recognition abilities. This study examined whether their word recognition was related to the use of either highly dynamic or relatively steady-state vowel cues contained in /bVb/ and /wVb/ syllables. Nine conditions were created containing different combinations of formant transition, steady-state, and duration cues. Because processor strategies differ, the ability to perceive static and dynamic information may depend on the type of cochlear implant used. Ten Nucleus and ten Ineraid subjects participated, along with 12 normal-hearing control subjects. Vowel identification did not differ between implanted groups, but both were significantly poorer at identifying vowels than the normal-hearing group. Vowel identification was best when at least two kinds of cues were available. Using only one type of cue, performance was better with excised vowels containing steady-state formants than in "vowelless" syllables, where the center vocalic portion was deleted and transitions were joined. In the latter syllable type, Nucleus subjects identified vowels significantly better when /b/ was the initial consonant; the other two groups were not affected by specific consonantal context. Cochlear implant subjects' word-recognition was positively correlated with the use of dynamic vowel cues, but not with steady-state cues. PMID- 1619126 TI - Formant frequency discrimination by Japanese macaques (Macaca fuscata). AB - These studies investigated formant frequency discrimination by Japanese macaques (Macaca fuscata) using an AX discrimination procedure and techniques of operant conditioning. Nonhuman subjects were significantly more sensitive to increments in the center frequency of either the first (F1) or second (F2) formant of single formant complexes than to corresponding pure-tone frequency shifts. Furthermore, difference limens (DLs) for multiformant signals were not significantly different than those for single-formant stimuli. These results suggest that Japanese monkeys process formant and pure-tone frequency increments differentially and that the same mechanisms mediate formant frequency discrimination in single formant and vowel-like complexes. The importance of two of the cues available to mediate formant frequency discrimination, changes in the phase and the amplitude spectra of the signals, was investigated by independently manipulating these two parameters. Results of the studies indicated that phase cues were not a significant feature of formant frequency discrimination by Japanese macaques. Rather, subjects attended to relative level changes in harmonics within a narrow frequency range near F1 and F2 to detect formant frequency increments. These findings are compared to human formant discrimination data and suggest that both species rely on detecting alterations in spectral shape to discriminate formant frequency shifts. Implications of the results for animal models of speech perception are discussed. PMID- 1619127 TI - Pitch and voiced/unvoiced determination with an auditory model. AB - In this paper, an accurate pitch and voiced/unvoiced determination algorithm for speech analysis is described. The algorithm is called AMPEX (auditory model-based pitch extractor) and it performs a temporal analysis of the outputs emerging from a new auditory model. However, in spite of its use of an auditory model, AMPEX should not be regarded as a substitute for any psychophysical theory of human auditory pitch perception. What is mainly described is the design of a computationally efficient auditory model, the perceptually motivated determination of the model parameters, the conception of a reliable pitch extractor for speech analysis, and the elaboration of an experimental procedure for evaluating the performance of such a pitch extractor. In the course of the evaluation experiment several kinds of speech stimuli including clean speech, bandpass-filtered speech, and noisy speech were presented to three different pitch extractors. The experimental results clearly indicate that AMPEX outperforms the best algorithms available. PMID- 1619128 TI - Effects of musical training and absolute pitch ability on event-related activity in response to sine tones. AB - The neural correlates of music perception have received relatively little scientific attention. The neural activity of listeners without musical training (N = 11), highly trained musicians (N = 14), and musicians possessing "absolute pitch" (AP) ability (N = 10) have been measured. Major differences were observed in the P3, an endogenous event-related potential (ERP), which is thought to be a neurophysiological manifestation of working memory processing. The P3 was elicited using the classical "oddball" paradigm with a sine-tone series. Subjects' musical backgrounds were evaluated with a survey questionnaire. AP ability was verified with an objective pitch identification test. The P3 amplitude, latency and wave shape were evaluated along with each subjects' performance score and musical background. The AP subjects showed a significantly smaller P3 amplitude than either the musicians or nonmusicians, which were nearly identical. The P3 latency was shortest for the AP subjects, and was longer for the nonmusicians. Performance scores were uniformly high in all three groups. It is concluded that AP subjects do indeed exhibit P3 ERPs, albeit with smaller amplitudes and shorter latencies. The differences in neural activity between the musicians and AP subjects were not due to musical training, as the AP subjects had similar musical backgrounds to the musician group. It is also concluded that persons with the AP ability may have superior auditory sensitivity at cortical levels and/or use unique neuropsychological strategies when processing tones. PMID- 1619129 TI - Formant frequencies in Estonian folk singing. AB - Formant frequencies in an old Estonian folk song performed by two female voices were estimated for two back vowels /a/ and /u/, and for two front vowels /e/ and /i/. Comparison of these estimates with formant frequencies in spoken Estonian vowels indicates a trend of the vowels to be clustered into two sets of front and back ones in the F1/F2 plane. Similar clustering has previously been shown to occur in opera and choir singing, especially with increasing fundamental frequency. The clustering in the present song, however, may also be due to a tendency for a mid vowel to be realized as a higher-beginning diphthong, which is characteristic of the North-Estonian coastal dialect area where the singers come from. No evidence of a "singer's formant" was found. PMID- 1619130 TI - Reduction of tympanic membrane displacement during vocalization of the arboreal frog, Eleutherodactylus coqui. AB - Tympanic membrane (TM) velocities of vocalizing male frogs, Eleutherodactylus coqui, were measured in the field using laser vibrometry. The animal's call produced levels of 114-120 dB SPL measured at distances of 12-20 mm from the eardrum and mean TM displacements in response to the two notes of the male's own advertisement call were 1.84 and 2.08 nm, respectively. These values are close to the TM displacements obtained in response to playback of the two-note call at much lower sound levels. Thus TM vibrations are attenuated during phonation in the frog, and several candidate mechanisms for auditory sensitivity reduction are discussed. PMID- 1619131 TI - The role of interaural time difference and fundamental frequency difference in the identification of concurrent vowel pairs. PMID- 1619132 TI - Premorbid behavioral and psychosocial adjustment of children with traumatic brain injury. AB - The premorbid adjustment of 85 six- to sixteen-year-old children with traumatic brain injury was assessed by means of standardized rating forms that were completed by the children's parents and teachers. Parents and teachers were in moderate agreement when rating children's premorbid functioning. Less than 11% of the children appeared to have premorbid disturbances. Premorbid adjustment did not appear to be clearly related to injury severity or to type of injury. It is concluded that premorbid behavioral and psychosocial factors are not strongly related to the incidence of traumatic brain injury in a sample of children with predominantly relatively severe injuries. PMID- 1619133 TI - Prevention and treatment of juvenile problem behavior: a proposal for a socio ecological approach. AB - This study proposes a socio-ecological model representing the relation between emotional and behavioral problems of children and risk factors in the family, at school and in the peer group. An empirical examination of a sample of 150 children at risk for delinquency shows that the model explains 30-40% of the variance in problem behavior. The model is used to provide possibilities for prevention and intervention. PMID- 1619134 TI - Adolescents with attention deficit hyperactivity disorder: mother-adolescent interactions, family beliefs and conflicts, and maternal psychopathology. AB - A group of 83 adolescents with attention deficit hyperactivity disorder (ADHD) were subdivided into those with ADHD alone (n = 27) and those with ADHD and oppositional defiant disorder (ADHD/ODD, n = 56). They were compared to each other and a community control group (n = 77) on measures of family conflicts, family beliefs, maternal adjustment, and observations of mother-adolescent interactions during both a neutral and conflict discussion. Both ADHD groups had more topics on which there was conflict and more angry conflicts at home than control adolescents on parent reports. Only the ADHD/ODD adolescents reported more such conflicts, endorsed more extreme and unreasonable beliefs about their parent-teen relations, and demonstrated greater negative interactions during a neutral discussion than the control teenagers. Similarly, only mothers of the ADHD/ODD teens displayed greater negative interactions during a neutral discussion, more extreme and unreasonable beliefs about their parent-teen relations, greater personal distress, and less satisfaction in their marriages than the mothers in the control group. Most findings for the ADHD only group were between the control group and the group with mixed ADHD/ODD but did not differ from either group. Results imply that it is the combination of ODD symptoms with those of ADHD that is associated with the greater-than-normal conflicts, anger, poor communications, unreasonable beliefs, and negative interactive styles seen in ADHD adolescents. These same characteristics typify their mothers' interactions as well such that both the adolescents' ODD symptoms and maternal psychological distress (hostility) make unique contributions to the degree of conflict and anger in the parent-teen relations of ADHD adolescents. PMID- 1619136 TI - Correlates of sociometric status in school children in Buenos Aires. AB - Teacher ratings on Spanish translations of the Comprehensive Behavior Rating Scale for Children and peer nominations were obtained for 110 school children (42 boys and 68 girls) in grades 2-5 at a public elementary school in Buenos Aires. Nominations of "likes best" were negatively correlated with language processing deficits, attention problems, and sluggish tempo as rated by both teachers and peers, and positively correlated with teacher ratings of social competence, for both boys and girls. The reverse pattern was found for nominations of "likes least." Children were assigned to sociometric status groups of popular (n = 27), rejected (n = 28), neglected (n = 7) controversial (n = 11), and average (n = 37) based on number of LL and LB nominations. Rejected and popular children could be differentiated by teacher and peer ratings of linguistic information processing deficits, inattention, and sluggish tempo. Behavioral characteristics of motor hyperactivity, impulsivity, and aggression were significantly associated with being male but did not differ by sociometric status group. PMID- 1619135 TI - Attention, play, and social behavior in ADHD preschoolers. AB - We investigated attention, play and nonplay behavior in preschool children with attention deficit hyperactivity disorder (ADHD) and a matched control group of non-ADHD children. Forty 4- to 5-year-old children (20 ADHD and 20 matched control) participated. Across a 6-week-period, children's social and play interactions as well as nonplay behaviors were videotaped in the classroom. Videotape recordings were analyzed for the level of attention, cognitive play, and social participation. In addition, children's level of attention and cooperative behavior were observed during two group activities. Findings indicated that ADHD, relative to non-ADHD, children engaged in less overall play and greater functional or sensorimotor play. ADHD children also engaged in more transitional behavior, were less competent with peers, and were less attentive and cooperative during group activities. PMID- 1619137 TI - Development of conduct problems and peer rejection in preschool children: a social systems analysis. AB - The development of impulsive-aggressive problem behavior and peer rejection was examined in sixty 4- to 5-year-old boys from low-income family backgrounds. Children's sociometric status and behavioral adjustment were assessed longitudinally at the beginning and end of the preschool year, and related to measures of peer interaction at three different points in time. Boys identified as socially rejected and aggressive in the beginning of the year were highly likely to be identified as such at the end of the year. Early in the preschool year, these children contributed to their own rejection by initiating socially aversive exchanges with peers. Although peers clearly perceived these problems, they did not reciprocate with counteraggression at first. However, as time passed, peers began to actively victimize these children, and most of the aggression on the part of victims became reactive in nature. Thus, the current findings strongly support a transactional model of the development of early peer rejection and conduct problems. PMID- 1619138 TI - Dental CAD/CAM. PMID- 1619139 TI - More on molars. PMID- 1619140 TI - Importance of critical reading. PMID- 1619141 TI - NIDR funds AIDS study. PMID- 1619142 TI - New approaches to preventing and treating postoperative pain. AB - Dental pain is estimated to account for 15 million lost U.S. work days each year. A flexible analgesic scheme, described in this report, can effectively manage acute pain so patients won't avoid dental treatment they perceive as painful. PMID- 1619143 TI - Managing anxiety and pain during dental treatment. AB - Behavioral techniques can teach patients how to cope with anxiety and tension while undergoing dental procedures. Practitioners need to know which technique best fits each patient. This report reviews the repertoire of procedures. PMID- 1619144 TI - Managing TMD patients: initial therapy is the key. AB - It has been the intention of this brief paper to help dentists respond quickly and effectively to patients with TMD. (In lieu of a detailed bibliography, a brief list of articles and books that deal with diagnosis and therapy for TMD follows.) Several present actual guidelines for practice, while others discuss concepts in greater detail. Knowing how to help these troubled patients by using contemporary basic principles of pain management should make every practicing dentist feel a well-deserved sense of fulfillment. PMID- 1619145 TI - Controlling dental pain. AB - The obligation to manage pain and relieve a patient's suffering is an important part of dentistry. The practitioner must balance pain control, concern for patient safety and side effects of pain treatment. There are no rigid prescriptions to manage postoperative pain. PMID- 1619146 TI - Preventing dental caries: breaking the chain of transmission. AB - Besides using all possible techniques to increase host resistance (fluoride, sealants) and decrease exposure to fermentable carbohydrates (for example, use of sugar substitutes), dentists must treat caries as infectious and transmissible. Antimicrobial agents are recommended. PMID- 1619147 TI - Phenytoin-induced hyperplasia found in edentulous patients. PMID- 1619148 TI - Tooth restorations for mature people: some new hope with new materials. PMID- 1619149 TI - Clinical board examinations: variation found in pass rates. AB - This study found significant variation in pass rates within and among state and regional dental board clinical examinations during 1979-1988. This suggests that factors other than the abilities of the candidates influence exam outcomes. As long as individual states can argue that there is currently no definitive system to assure the quality of dental care, states may remain reluctant to relax their restrictions on dentists' freedom of movement. PMID- 1619150 TI - Non-maleficence: do no harm! PMID- 1619151 TI - Creating your practice philosophy: it's your chance to set goals. PMID- 1619152 TI - Microbiology of the mouth. PMID- 1619153 TI - Sterilization and disinfection. PMID- 1619154 TI - Infection control. PMID- 1619155 TI - Blood analysis. PMID- 1619156 TI - OSHA guidelines. PMID- 1619157 TI - Antisealants. PMID- 1619158 TI - Licensure. PMID- 1619159 TI - Patient medication costs as a therapeutic consideration. AB - Don't neglect therapeutic considerations in selecting drugs, but take their cost into account. Sometimes, selecting an older, established drug or generic equivalent can represent a significant savings for the patient. PMID- 1619160 TI - Rationale for removing impacted teeth: when to extract or not to extract. AB - Age, crowding, disease and root resorption all influence the decision to remove impacted teeth. While not every impacted tooth causes a significant problem, each has that potential. PMID- 1619161 TI - Cranial bone grafting in oral and maxillofacial surgery. PMID- 1619163 TI - Patient fights for right to records. PMID- 1619162 TI - FDA explains status of N2 material. PMID- 1619164 TI - Ceramic orthodontic brackets: how and when to use them. Council on Dental Materials, Instruments and Equipment. PMID- 1619165 TI - States take the lead on health care reform. PMID- 1619166 TI - Risk management: then and now. PMID- 1619167 TI - Using posterior composites appropriately. AB - The success rates of posterior composite restorations vary depending on whether they are used in clinical studies or by practitioners. This article offers a guide to determining when to use these materials. PMID- 1619168 TI - Alternative therapies for major aphthous ulcers in AIDS patients. PMID- 1619169 TI - Report of case: reviewing cephalic tetanus. AB - In this case, either caries or a root canal procedure provided the point of entry for cephalic tetanus. Facial/head pain may signal the first symptom. PMID- 1619170 TI - Ingesting an onlay. A case report. AB - When a patient attempted to speak during a dental procedure, she swallowed an onlay. After four weeks, it was mechanically removed from her colon. PMID- 1619171 TI - The key to an active practice? It's continuing patient education. PMID- 1619172 TI - A matter of trust. PMID- 1619173 TI - Point of view defining a nutritious diet: need for new dietary standards. PMID- 1619174 TI - Nutritional management of the obese gestational diabetic pregnant woman. PMID- 1619175 TI - Caloric restriction in pregnant diabetic women: a review of maternal obesity, glucose and insulin relationships as investigated at the University of California, San Diego. AB - Caloric restriction during pregnancy is contraindicated for women with a normal body mass index (BMI) of 19.8-26 kg/m2. Reduction of caloric intake in obese pregnant normal and diabetic women has been a controversial topic for many years. This paper reviews several clinical studies initiated in 1978 at the University of California, San Diego. One focus of this review concerns modest caloric reduction in obese women with gestational diabetes mellitus (GDM). Metabolic observations of diabetes during pregnancy in the past decade include extensive use of a 400 kcal isocaloric breakfast meal tolerance test to assess maternal glucose:insulin relationships and the degree of insulin resistance in obese pregnant subjects. We have previously reported that maternal hyperinsulinemia with or without maternal hyperglycemia is an important factor in fetal macrosomia. We suggest for obese pregnant diabetic women implementation of nutritional recommendations of the 1990 Committee on Nutritional Status During Pregnancy and Lactation, Food and Nutrition Board, Institute of Medicine, National Academy of Sciences that advise a lower caloric intake for obese normal pregnant women with BMIs greater than 26. In obese noninsulin-dependent diabetic women and those with GDM, we urge that a large prospective epidemiologic study be undertaken to assess the respective roles of modest maternal caloric restriction and maternal glucose:insulin relationships on neonatal and long-term longitudinal measurements of growth and development of children of diabetic mothers. PMID- 1619176 TI - Caloric restriction in gestational diabetes mellitus: when and how much? AB - Variations in nutritional intake during pregnancy have measurable effects on the circulating levels of maternal nutrients, maternal weight gain, and birth weight of the offspring. A growing body of evidence indicates that alterations in maternal metabolism can also have long-term consequences in the offspring in relation to adult adiposity, glucose tolerance, and perhaps intellectual development. Therefore, recommendations for diet during pregnancy must be made with great care, and with as much scientific understanding as possible. Nutritional advice traditionally given to all pregnant women, including those with gestational diabetes mellitus (GDM) or noninsulin-dependent diabetes, does not allow for individual differences in caloric needs as a function of the degree of maternal obesity and thus, may encourage excessive weight gain. Evidence reviewed below suggests that adjusting caloric intake to meet new guidelines for weight gain during pregnancy may be advantageous in reducing maternal blood sugar and insulin levels, without producing abnormalities in other metabolic variables. Modest caloric reduction which limits excessive weight gain in the mother may also be associated with a small reduction of fetal weight. However, more stringent dietary manipulations in obese gravida should be discouraged as a routine measure until more knowledge is available from large-scale clinical trials about their effects on the entire panoply of maternal nutrients and their impact on the offspring. PMID- 1619178 TI - Effect of daytime on resting energy expenditure and thermic effect of food in obese adolescents. AB - The aim of this study was to investigate the effect of daytime on resting energy expenditure (REE) and thermic effect of food (TEF), REE and TEF were measured in 11 obese boys (mean age +/- SD 11.9 +/- 1.6 years; body mass index 30.1 +/- 4.0 kg/m2) by indirect calorimetry (SensorMedics 2900) on two consecutive days: early in the morning (7:30 a.m.) on one day and at 12 noon on the other day or vice versa. REE was measured for 30 minutes and TEF for 180 minutes after a 600 kcal liquid meal containing 13% protein, 39% fat and 48% carbohydrates. REE measured in the morning was not statistically different from that measured at noon (2191 +/- 358 vs 2223 +/- 319 kcal/24 hours) and morning values were highly correlated with afternoon values (r2 = 0.805). Therefore we conclude that the effect of daytime is negligible for measurements of REE if the patients are in a postabsorptive state and avoid physical activity and stress 10-12 hours prior to measurements. The thermic effect of food calculated in the morning also was not statistically significantly from values found in the afternoon (8.2 +/- 8.8% in the morning and 6.6 +/- 7.5% in the afternoon). However, because of very high within-patient variability the correlation between morning and afternoon values was weaker than for REE (r2 = 0.289). PMID- 1619177 TI - Brief communication: changes in thermogenesis and caloric efficiency with high and normal protein-reducing diets in women. AB - A pilot study with four women (40-60% above ideal weight, 32-42 years old) was conducted for 6 weeks of weight maintenance, 12 weeks at 50% calories (1000 and 1200 kcal/day) and 6 weeks of weight maintenance after weight loss. Two women consumed 17% and two 32% of their calories from protein during restriction; their energy metabolism and body composition changes were examined. The use of doubly labeled water for measuring energy expenditure during weight loss was evaluated. Although the 32% protein diet did not reduce lean body tissue loss, the apparent increased efficiency of calorie utilization compared to the 17% protein diet is worthy of further investigation. Thermic effect of a meal was greatly reduced in these women compared to previously reported responses. Further refinements of the doubly labeled water method are needed prior to application in weight loss studies. PMID- 1619179 TI - Thiamin and vitamin B6 intakes and erythrocyte transketolase and aminotransferase activities in morbidly obese females before and after gastroplasty. AB - To assess the need for postoperative vitamin supplements, intakes and nutritional status of thiamin (B1) and vitamin B6 were studied in 18 female gastroplasty patients who received a placebo or different levels of supplemental vitamins. Postoperative erythrocyte transketolase basal (BA) and thiamin pyrophosphate stimulated (SA) activities and activity coefficients (AC) correlated significantly with B1 intake. Despite a decrease in apotransketolase, low thiamin intakes were associated with increased AC values during the first 3 months. With return to low B1 intakes following repletion during month 4, the AC values remained normal with low total activities. Both alanine (EALT) and aspartate (EAST) aminotransferase apoenzyme levels declined and AC values increased significantly during the first 3 months. Although the EALT-indices were more sensitive to changes in B6 intake than the EAST-indices, the EASTBA and SA correlated most consistently with the intake. Postoperative dietary intakes of both vitamins were inadequate for maintenance of normal activities of these erythrocyte enzymes. Although B1 intake of greater than or equal to 1.0 mg/day was adequate for maintenance of normal thiamin status in most subjects of this study, supplementation with greater than or equal to 1.5 mg/day is prudent even though it may not prevent the early postoperative loss of apotransketolase. Vitamin B6 intake at the current recommended dietary allowance (1.6 mg) was not adequate to maintain coenzyme saturation of the erythrocyte aminotransferases. Marginal intake of other nutrients may have affected the utilization of both thiamin and vitamin B6. PMID- 1619180 TI - Dietary intake, exercise, obesity and noncommunicable disease in rural and urban populations of three Pacific Island countries. AB - Dietary intake surveys of rural and urban communities in three Pacific Island countries were conducted using an adjusted 24-hour dietary recall method. Dietary survey samples were drawn from noncommunicable disease surveys of Melanesians and Indians in Fiji, Micronesians in Kiribati and Melanesians in Vanuatu. Comparisons of total energy and macronutrient intakes and of obesity, hypertension, diabetes mellitus, serum cholesterol and physical activity levels revealed similar rural/urban trends. Urban subjects were more obese than rural ones, had higher prevalence rates of diabetes and hypertension, and generally had higher cholesterol levels. Rural subjects were leaner, suffered less from diabetes and hypertension, and had greater total energy intakes than urban dwellers. Rural people ate a greater proportion of carbohydrates, while urban subjects ate proportionally more protein and fat, apart from the outer Kiribati atolls with high coconut intakes. Rural subjects in all three studies had higher levels of physical activity. These studies provide persuasive evidence that exercise as well as diet has a significant effect on rural/urban differentials in obesity and noncommunicable disease, and that energy intake reflects energy expenditure. PMID- 1619181 TI - Plasma lipoproteins in hyperlipidemic subjects eating iodine-enriched eggs. AB - Iodine-enriched (IE) eggs are produced by chickens fed a diet containing kelp. These eggs have been reported to reduce plasma cholesterol in humans and experimental animals. The purpose of this study was to determine the effect of the ingestion of one IE egg/day on the plasma lipoprotein cholesterol in borderline and hyperlipidemic individuals ingesting a low-fat diet. One hundred three subjects with entry cholesterol levels greater than 5.17 mmol/L were placed on a low-fat, low-cholesterol diet for 12 weeks. Between weeks 4 and 12, approximately half of the subjects were randomly assigned to either a diet control group (n = 53), or a group who ingested one IE egg/day in addition to this diet (n = 50). Subjects in both the egg group and the diet control group had a significant reduction in total plasma cholesterol (TC) at the end of the study compared with study entry; addition of the egg in the diet did not abolish the TC reduction in the egg group. However, paired comparisons of total and lipoprotein cholesterol levels at the end of the egg intervention period with the end of the initial dietary period demonstrated that the egg group had a significantly greater increase than the diet control group in TC (egg group: 7.2 +/- 1.5% increase; diet controls: 1.5 +/- 0.9% increase; p less than 0.01) and low-density lipoprotein cholesterol (egg group: 9.2 +/- 1.7% increase; diet controls: 3.9 +/- 1.5% increase; p less than 0.01). This effect was most pronounced in subjects with higher initial cholesterol levels and subjects with mixed hyperlipidemia (elevated cholesterol and triglyceride). Results suggest that these particular groups of subjects are most susceptible to cholesterol changes associated with ingestion of IE eggs. PMID- 1619182 TI - Omega-3 fatty acid content of the US food supply. AB - In this study, levels and sources of omega-3 fatty acids (FA) available for consumption in the US food supply, dating from 1935, are estimated. omega-3 FA assessed are eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and linolenic acid (LNA). Estimates are based on annual per capita food use data and data on the omega-3 FA content of foods. Although fish use increased, the EPA level was slightly lower in 1985 than in 1935-1939, reflecting a marked decline in use of certain fatty fish. The level of DHA increased, due to greater use of poultry. The level of LNA increased because of greater use of soybean oil. These estimates are currently the only source of data on omega-3 FA in the American diet. PMID- 1619183 TI - Prolonged tube feeding in long-term care: nutritional status and clinical outcomes. AB - This study examines nutritional status and clinical outcomes, including pressure ulcers and death in 40 chronically tube-fed long-term care patients. Anthropometric, biochemical, clinical and dietary data were collected over a 3 month period, with follow-up of mortality at 1 year. Subjects' functional and cognitive status was generally poor. Adequate calories and protein were provided, with sample means exceeding standard means for energy, protein and micronutrients. Still, subjects showed weight loss and severe depletion of lean and fat body mass. Mean serum protein and micronutrient status measures were in the low normal range. Hemoglobin, hematocrit, and serum zinc and carotenoid levels were below normal in a sizable proportion of patients. Pressure ulcers were present in 65% of patients. Weight loss was associated with longer time on tube feeding and more pressure ulcers. Negative correlations with ulcer number were observed for cholesterol, albumin, zinc, retinol, alpha-tocopherol and iron. This study shows that despite administration of apparently adequate formula, micronutrient deficiencies and marasmic malnutrition exist in chronically ill patients. Causes may include the combined effects of chronic disease, sepsis, immobility, and severe neurologic deficits. Clinical outcomes may be expressions of an organism-wide diminution of protein synthesis, the cause of which is unknown. For clinical management, serial measures of weight, albumin, cholesterol, hemoglobin and hematocrit are recommended. Future research must address the many subsets of the population of chronically tube-fed patients. PMID- 1619184 TI - Effect of magnesium supplementation on strength training in humans. AB - This study investigated the effects of dietary magnesium (Mg) on strength development during a double-blind, 7-week strength training program in 26 untrained subjects (14 = control, C and 12 = Mg supplemented, M), 18-30 years old. Subjects' 3-day diet records were analyzed and Mg content was calculated. C received a placebo and M received a supplement (Mg oxide) to bring Mg intake, including diet, to 8 mg/kg body weight/day. Body composition was assessed with bioelectrical impedance. Pre and post quadriceps torque (T) measurements were made with an Orthotron at 120 deg/sec. Each subject performed three sets of 10 reps, leg press and leg extension, three times/week. Both groups gained strength, however, results indicated a significant (p less than 0.05) increase for the M group compared to the C group in absolute T, relative T adjusted for body weight (T/BWT), and relative T adjusted for lean body mass (T/LBM) when pre values were used as the covariate. M was consistently greater than C (T: 211 vs 174 Nm; T/BWT: 3.07 vs 2.58 Nm/kg; T/LBM: 3.84 vs 3.36 Nm/kg). CONCLUSION: Significant differences in T gains after strength training were demonstrated in M vs C. Mg's role may be at the ribosomal level in protein synthesis. PMID- 1619185 TI - Cardiomyopathy of copper deficiency: effect of vitamin E supplementation. AB - The present study was undertaken to determine whether the intraperitoneal injection of vitamin E to copper-(Cu) deficient rats fed fructose will protect the animals against the severity of Cu deficiency. Cu-deficient and adequate rats were fed a diet containing 62% carbohydrate as fructose. Half the Cu-deficient rats fed fructose were injected daily with vitamin E. Vitamin E treated rats were not protected against the lethal consequences of the interaction between Cu and fructose. These data provide evidence that the cardiomyopathy of Cu deficiency in rats consuming a fructose-based diet cannot be ameliorated by vitamin E supplementation. PMID- 1619186 TI - Garlic oil extract ameliorates the severity of copper deficiency. AB - This study was undertaken to determine whether a reduction in hepatic lipogenesis would be beneficial in the amelioration of copper (Cu) deficiency when fructose is fed. Garlic was chosen as the agent for reducing hepatic lipogenesis. Forty eight weanling rats were fed Cu-deficient or adequate diets containing fructose or starch with or without garlic for 5 weeks. Garlic ameliorated the signs associated with Cu deficiency, although hepatic lipogenesis was not affected. Administration of garlic reduced the activity of the lipogenic enzyme glucose-6 phosphate dehydrogenase only in Cu-adequate rats. Consumption of garlic resulted in increased epididymal fat pad and pancrease sizes, and higher hematocrits, insulin and thyroxine concentrations. Mechanisms other than lipogenesis that could be responsible for this phenomenon are discussed. PMID- 1619187 TI - Why aluminum phosphate is less toxic than aluminum hydroxide. AB - Initially characterized in uremic patients undergoing hemodialysis, toxic effects due to high aluminum (Al) body loads were subsequently observed in a number of conditions, in particular following ingestion of Al-containing antacids. Among compounds of this class, aluminum phosphate (AlPO4) was recognized as safer than aluminum hydroxide (Al(OH)3), which was thought to result from its lower solubility and thus absorption in the gastrointestinal (gi) tract. However, while virtually insoluble at acid pH, AlPO4 is more soluble than Al(OH)3 under alkaline conditions, leading to the hypothesis that Al is predominantly absorbed in the acidic region of the gi tract. Our present results suggest otherwise. Al bioavailability depends on the solubility of the salt ingested as well as on the physicochemical properties of the Al soluble complexes formed in the gi fluid. Anions of dietary acids may indeed dissolve significant fractions of Al salts and form absorbable Al complexes. It is in these terms that the well documented increase of Al gi absorption by citrate has been interpreted from computer-based speciation studies. Using similar calculations, we now demonstrate that a series of dietary acids (namely malic, oxalic, tartaric, succinic, aspartic and glutamic acids) can also dissolve significant amounts of Al(OH)3 and form Al neutral complexes available to the gi membrane. In contrast, both effects are far less apparent when Al is administered as AlPO4. We conclude from this observation that the lower toxicity of AlPO4 vs Al(OH)3 stems from its better capacity to resist dissolution and neutral complex formation in the presence of acids commonly present in food. PMID- 1619188 TI - Oral diet does not alter pulmonary pentane or ethane excretion in healthy subjects. AB - Ethane and pentane are alkanes that are excreted through the lungs to a small degree in healthy subjects. These gasses are produced from the peroxidation of unsaturated fats which are found both in body tissues and in foods. These gasses are excreted in larger amounts by patients with increased production of reactive oxygen metabolites, including those with inflammation or ischemia. Thus, detection of these gasses in excessive quantities is considered evidence for lipid peroxidation. However, the effects of dietary factors on these measurements have not been defined. To define the effects of eating on the pulmonary excretion of these alkanes, 29 healthy subjects were fed a standardized liquid diet (1060 kcal, 12.9 g linoleic acid and 385 mg linolenic acid) after an overnight fast. Breath alkanes were measured at 0, 1, 3, and 6 hours. All subjects had normal vitamin E (1.11 + 0.26 mg/dl), retinol (64 +/- 14 micrograms/dl), beta carotene (27 +/- 21 micrograms/dl), lycopene (23 +/- 12 micrograms/dl) and zinc (81.9 +/- 13.5 micrograms/dl) levels. No statistically significant changes in either alkane were noted relative to the fasting level. We conclude that oral diet does not alter pulmonary ethane or pentane excretion in healthy subjects. PMID- 1619189 TI - Changes in serum and urinary uric acid levels in normal human subjects fed purine rich foods containing different amounts of adenine and hypoxanthine. AB - The effect of ingesting some purine-rich foods (beef liver, haddock fillets and soybeans) on uric acid metabolism was investigated in 18 male subjects with no history of gout or kidney disorder. In a crossover design, three isoenergetic and isonitrogenous meals were fed to volunteers during a 3-week period. Only the content of uricogenic bases (adenine and hypoxanthine) varied among the test meals. Ingestion of all experimental meals caused an increase in serum uric acid levels at 120 minutes and this increase was more marked (about twofold) with haddock and soybean ingestion. In all groups, the postprandial serum uric acid levels at 240 minutes were lower than those obtained at 120 minutes, but still remained elevated in comparison to the fasting level. The test foods had little or no effect on serum and urinary creatinine values. As expected, 24-hour urinary uric acid excretion was similar for the three test meals due to the isonitrogenous load of proteins and purines. Assessment of each purine base content rather than the total purine content of foods should be considered in future recommendations for hyperuricemic individuals. PMID- 1619190 TI - Conclusions, guidelines and recommendations from the IUNS/WHO Workshop: nutrition in the pediatric age group and later cardiovascular disease. PMID- 1619191 TI - Position statement: the 'pros' of cholesterol screening of children. PMID- 1619192 TI - Position statement: the 'cons' of cholesterol screening of children. PMID- 1619193 TI - Position statement: cholesterol screening in children is not indicated, even with positive family history. AB - The same reasons for the policy of rejecting universal blood cholesterol screening in all children also lead us to reject selective screening in those with a family history of premature CHD or high blood cholesterol. It is probably true that this large group--roughly 25% of all children, 12 million in the United States and many tens of millions worldwide--is at somewhat higher risk than the other 75% of children of eventually dying of CHD many decades later. But the small size and remoteness of any benefit achieved by cholesterol intervention is illustrated by the projection that we would need to treat 300 girls in the top cholesterol quintile, and treat them effectively for 50-60 years, in order to defer just one premature CHD death before age 65. The benefits of cholesterol screening and treatment in children are not only very small and remote, they are also uncertain; we have no firm evidence that they exist. The benefits are not needed, given the clinical trial evidence that most of the risk associated with high blood cholesterol among adults is reversible, even when intervention is not begun until middle age. The harmful effects of cholesterol screening and treatment are more firmly established than the benefits, and some are very serious. Such a program would be expensive orders of magnitude from conventional criteria for cost effectiveness. It would cause malnutrition in some children, and have the adverse consequences of labelling.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619194 TI - Cholesterol blood levels in children: comparison of a Munich screening to worldwide studies from 1980 to 1990. AB - Total cholesterol results of a screening of 134 Munich school children aged 6-11 years are described. In reviewing worldwide studies on blood lipids in children, in the last 10 years, I note a large variance in the so-called "normal" values, with mean levels of total cholesterol ranging from 148 to 214 mg%. Age-, sex-, and race-specific reference data for a population are needed. Only with these special data can one determine the point for intervention. With school health education programs, including medical screening examinations, the aim of primary prevention of coronary heart disease can be reached. PMID- 1619196 TI - Primary prevention of cardiovascular disease in childhood: recent knowledge and unanswered questions. AB - Efforts at prevention of chronic disease in adult life must include investigation of causal pathogenetic clues in early life. There is adequate rationale for identification of children who are at risk of developing cardiovascular disease (CVD) in later years. At the present time, practical considerations would favor a selective rather than universal screening of children. If the latter is instituted, then it is ideal to test children 4-7 years of age. In either case, total cholesterol greater than 200 mg/dl warrants a complete lipid-lipoprotein profile. Those with confirmed abnormal values of total cholesterol, low-density lipoprotein cholesterol, and apolipoproteins A1 and B should be offered dietary advice and encouraged to participate in regular exercise. In a few cases, drug therapy would be required. Limited data suggest that an integrated approach will result in a reduction of cardiovascular risk factors. Perinatal nutrition also may influence the risk of CVD among adults; a reduction in the prevalence of low birth weight and prevention of failure to thrive in early infancy may be additional useful strategies for prevention of CVD. PMID- 1619195 TI - Cholesterol and lipoprotein levels in Milanese children: relation to nutritional and familial factors. AB - Dyslipidemia is a major risk factor for atherosclerosis in adults and children. This study investigated the levels of lipoproteins in a northern Italian pediatric population, in relation to nutritional and familial factors. We studied 650 children on the basis of a 3-day dietary record; 361 of these children had their lipid levels [total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides] measured by a dry, multilayer method and apoprotein A I and B by an immunonephelometric method. Familial history of cardiovascular disease and dyslipidemia was recorded. Anthropometric variables were taken for each child. Mean TC and low-density lipoprotein cholesterol (LDL-C) were high compared with southern Italian data, but similar to those of other Western countries. Family history of cardiovascular disease could not identify children with higher levels of atherogenic lipoprotein. Nutritional factors affected lipoprotein levels. The most important finding was a higher TC/HDL-C ratio in the lower quartile of polyunsaturated fatty acid intake. Obese children had higher levels of ApoB, triglycerides, TC and LDL-C, and lower levels of HDL-C; figures were higher for obese boys than for obese girls. Our study confirms a high prevalence of elevated levels of atherogenic lipoproteins among the northern Italian pediatric population and an association with nutritional factors and weight. PMID- 1619197 TI - Serum lipids, lipoproteins and apolipoproteins in children with and without familial history of premature coronary heart disease. AB - A positive family history of premature cardiovascular disease is recognized as an independent predictor of risk for cardiovascular death in first degree relatives. It is of great interest whether the progeny of families with manifest coronary heart disease can be discriminated from children with a negative family history. Therefore, we examined serum lipids, lipo- and apolipoproteins in 338 offspring whose fathers and/or mothers had been affected with a myocardial infarction before the age of 55, in comparison with 448 age- and sex-matched, healthy controls. Statistical analyses revealed marked differences between the two groups: In both age groups only high-density lipoprotein cholesterol (HDL-C), as a single parameter, and the ratios of total cholesterol (TC)/HDL-C, as well as low-density lipoprotein cholesterol (LDL-C)/HDL-C, showed a significant difference between the risk and nonrisk groups. Whereas the ratio of apolipoprotein A1 (ApoAI) to apolipoprotein B is the strongest discrimination in children less than or equal to 20 years, the ratio of HDL-C/ApoAI takes this position in the older ones. Apolipoproteins seem to be of considerable importance as risk indicators between offspring who might be at higher risk for later cardiovascular diseases, even in childhood and younger adolescence. PMID- 1619198 TI - Cardiovascular risk factors in schoolchildren. AB - A total of 1470 students in Berlin, Germany, aged 7-22 years, were screened for cardiovascular risk factors such as hypercholesterolemia, hypertension, obesity, smoking habits, and a positive family history. Only 56% had no modifiable risk factor, but 16% showed total cholesterol (TC) levels greater than 200 mg/dl. One percent had severe and 11% had borderline hypertension. Also, 21% were overweight, and 27% of the adolescents greater than or equal to 15 years admitted to smoking regularly. In this paper we concentrate on cholesterol findings of this study, i.e., the dependence of TC on sex, age, weight, and the use of oral contraceptives. There was an age dependency in both sexes. In boys the lowest TC levels were found in the 12-17-year-olds, whereas the group under 10 had the highest ones. In the age group over 17, TC was higher than in the younger groups. The age dependency of the TC levels in girls was similar, but less pronounced. The minimum level was reached earlier, namely in the group 14-15 years old, rather than in the group 16-17. TC levels of girls compared to boys were significantly higher in the 12-13 and 16-17 age groups. Girls who use oral contraceptives had significantly higher TC levels. Obesity had no influence on TC. Our results support the demand for screening for cardiovascular risk factors in children. PMID- 1619199 TI - Cardiovascular risk factors in obese children in relation to weight and body fat distribution. AB - To assess the relationship between obesity and body fat distribution with cardiovascular risk factors in children, various measures of obesity and waist-to hip circumference ratio (WHR) were related to serum lipids, lipoproteins, apolipoproteins, glucose, insulin, uric acid, systolic (SBP) and diastolic blood pressure (DBP). In boys univariate analysis revealed an association of triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), the ratio ApoAI/ApoB, cholesterol/HDL-C, glucose and insulin to WHR. SBP and DBP and serum uric acid correlated with all measures of obesity [body mass index (BMI), percent overweight, percent body fat, skinfolds], but not with WHR. In girls lipid parameters (triglycerides, LDL-C, HDL-C, HDL2, ApoAI, ApoB) and atherogenic ratios correlated with measures of obesity and WHR. Glucose, insulin, SBP and DBP showed the highest correlation with WHR (r = 0.598, p less than 0.001 and r = 0.713, p less than 0.001). Multivariate analysis in girls revealed a first step dependency of ApoAI, the ratio cholesterol/ApoAI, insulin, SBP and DBP on WHR, triglycerides, HDL-C, LDL-C and the ratio ApoAI/ApoB, a first step dependency on percent body fat mass. In boys triglycerides, ApoB and the ratio ApoAI/ApoB were related to WHR for insulin, SBP and DBP, but a positive association with the WHR was found, explaining 33, 21.8, and 22.6% of the variance. This study demonstrates that cardiovascular risk factors in obese children are related to obesity and body fat distribution. Obese children with predominantly abdominal fat mass show a risk profile that is less favorable than gluteal-femoral fat distribution. Evaluation of body fat distribution in obese children, therefore, may help to identify persons most susceptible to cardiovascular risk in adulthood. PMID- 1619200 TI - Early lesions of atherosclerosis in childhood and youth: natural history and risk factors. AB - This paper traces the development of knowledge concerning early lesions of atherosclerosis and the relationship to risk factors in children, youth, and young adults. Autopsy studies have shown that atherosclerosis begins in childhood with the appearance of aortic fatty streaks. Aortic fatty streaks of some degree are present in practically all individuals from every human population. Coronary fatty streaks begin to form in adolescence. Most persons 20-29 years of age have coronary fatty streaks of some degree, regardless of sex, race, or national origin. While fatty streaking is clinically harmless and potentially reversible, progression to fibrous plaques and more advanced lesions often leads to a critical stage of atherosclerosis in which clinical disease develops. Development of fibrous plaques begins in the 20s. The most recent studies of atherosclerosis in youth and young adults provide additional details to establish the relationship of these lesions to serum lipids and lipoproteins and other identified risk factors for atherosclerosis and coronary heart disease in adults. One report shows that microscopic counterparts of fatty streaks occur in the left anterior descending coronary artery in the majority of children 10-14 years of age. Over 5% have more advanced microscopic lesions at this age. Autopsy studies of youth have shown that serum total cholesterol and low-density lipoprotein cholesterol levels are strongly related to aortic fatty streaks and the very-low density lipoprotein cholesterol levels are positively correlated to coronary artery fatty streaks. Finally, a definitive report indicates that serum lipoprotein cholesterol concentrations and smoking are important determinants of the early stages of atherosclerosis in adolescents and young adults. PMID- 1619201 TI - Predicting hypertension in childhood: value of blood pressure measurement and family history. AB - An elevated casual blood pressure (BP) in children and a positive family history for hypertension are risk indicators for adult hypertension. The risk of future hypertension is higher when BP levels in children or their parents are higher. Using multiple BP readings in children and their parents, groups of children can be discriminated with contrasting risks as a basis for studying the early phase of primary hypertension. Yet, as a means of detecting groups of children eligible for intervention, family history and BP level lack sensitivity for adequate selection. Before screening for future hypertension may be initiated successfully in prepubertal children, more should be known about the determinants and etiology of future BP rise. PMID- 1619202 TI - Diet and body lipid composition: lessons from animal and human experiments. AB - It is accepted that atherosclerosis begins early in life and will develop over several years. The type of diet fed to young rats and other mammals plays a role in the regulation of adult lipid homeostasis. Foods vary in fatty acid content. The importance of diet on lipid profile has been demonstrated in several animal studies and in different human population groups. Bridging the effect of early diet and later adult cardiovascular disease deserves decisive collaboration among different specialists, as well as preventive dietary intervention based on recent advances from food composition and dietotherapy. PMID- 1619203 TI - Effects of developmental changes and early nutrition on cholesterol metabolism in infancy: a review. AB - Plasma cholesterol levels usually range between 50 and 100 mg/dl at birth, with the cholesterol approximately equally distributed between low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Plasma cholesterol increases rapidly over the first days after birth, predominantly due to an increase in cholesterol with LDL, irrespective of whether the infant is breast fed or fed with infant formulas. With continued feeding, plasma cholesterol becomes progressively, and significantly, higher in infants who are breast fed compared to those fed low cholesterol, polyunsaturated fatty acid-rich infant formula. Studies in the developing young of other species have suggested that up-regulation of cholesterol synthesis, or turnover and excretion, at stages when these pathways are acquiring functional maturity may have lasting effects on cholesterol metabolism. The information available, however, indicates the diet-related differences in plasma cholesterol of the more mature human newborn are temporal in nature and probably not of significance to adult cardiovascular disease. Infants born early in the third trimester of gestation, however, are at risk for marked elevations in plasma cholesterol, with stimulation of endogenous cholesterol biosynthesis, as a result of the intravenous nutrition required to sustain life. Whether this has long-term consequences for this group of infants is unknown. There is presently no reason to advocate diet modification to alter the plasma cholesterol of normal infants under the age of 2 years. PMID- 1619204 TI - Influence of diets containing cow's milk or soy protein beverage on plasma lipids in children with familial hypercholesterolemia. AB - The present article summarizes the effects of diets containing either cow's milk or soy protein beverage on plasma lipids and lipoproteins in children with familial hypercholesterolemia. After a stabilization period of 6 weeks without any hypolipemic medication, 10 subjects aged 6-12 years were randomly assigned to either cow's milk or soy protein beverage with subsequent crossover after a washout period, each of 4 weeks duration. During the experimental periods, subjects were fed diets containing 20% of energy as protein, of which 35% was from cow's milk protein or soy protein isolate, 28% of energy as fat with a polyunsaturated:monounsaturated:saturated fat ratio of 1:3:3, and less than 200 mg/day of cholesterol. The soy protein beverage, compared to cow's milk, induced significant reductions in plasma triglycerides and very-low-density lipoprotein cholesterol, as well as a significant increase in high-density lipoprotein cholesterol, indicating that consumption of soy protein beverage may be beneficial for the prevention of coronary heart disease in children with familial hypercholesterolemia. PMID- 1619206 TI - Position statement: monounsaturated fatty acids in human nutrition. PMID- 1619205 TI - Achievable guidelines for food consumption to reach a balanced fat and nutrient intake in childhood and adolescence. AB - In many highly industrialized countries a reduction in the high average intake of fat, especially saturated fatty acids and cholesterol, has been recommended for the prevention of cardiovascular diseases for the general population, including children. However, it has not yet been shown that such a diet is generally achievable in childhood and that it meets the Recommended Dietary Allowances (RDA) for essential nutrients. Based on results of a nutrition survey using a 3 day weighing method for 350 German children and adolescents (1-14 years of age), achievable dietary modifications have been proposed to improve the observed nutrient intake (percentages of energy intake from protein:fat/saturated fatty acids:carbohydrates 13:39/18:48%). Age-related average daily quantities are given for 11 main food groups (e.g., milk, lean meat, visible fats, grain products, vegetables). The main proposals for food consuption are: avoidance of fatty meat and fatty meat products, reduction of fatty foodstuffs commonly consumed with bread and of foodstuffs with a high sucrose content and an increase in whole grain cereal products, potatoes and vegetables. The food consumption proposals are compatible with the typical meal patterns of German children and adolescents. Nutrient content of the proposed diet is presented. The proportions of protein:fat/saturated fatty acids:carbohydrates are 13:35/12:52% of total energy intake. It is shown that the US RDA for most of the calculated minerals, trace elements and vitamins can be met by the proposed balanced mixed diet without using special dietary products or products with added nutrients. PMID- 1619207 TI - Accurate measurement of serum total cholesterol: the need for standardization. AB - Heightened awareness of the importance of cholesterol and heart disease has increased cholesterol testing in the United States. The demand for reliable cholesterol measurements has become a focal concern of the patient as well as the clinician. This paper covers the major analytical and preanalytical issues and factors that can affect the reliability of cholesterol results. We discuss factors that lead to impression and inaccuracy; solutions for some of the major problems; resources and techniques to help standardize cholesterol measurement; and preanalytical issues that can affect cholesterol results--i.e., patient preparation; collection, processing, storage and proper analysis of the specimen; biological and seasonal variations; age and gender; diet; alcohol consumption; weight changes; exercise; primary diseases; and infections and trauma. Many of these can be controlled by the physician, resulting in more reliable cholesterol readings under stable metabolic conditions. Accurate values will help to classify the patient's coronary heart disease risk, define appropriate treatment strategies, and simplify monitoring of dietary and/or drug intervention. PMID- 1619208 TI - Position statement: nutrition options when reducing saturated fat intake. PMID- 1619209 TI - Children on adult diets: is it harmful? Is it healthful? AB - Physicians and parents are very concerned about providing children with the best nutrition and optimal diets. The pursuit of better health is one of the prime reasons for individual food choices. Often the main determinant in selecting food is a desire for a healthful diet that will foster longevity and prevent the devastating consequences of chronic degenerative disease. However, unlike nutritional deficiencies, which undoubtedly afflict those who consume an inadequate diet, the underlying causes of these chronic disorders are complex and poorly understood. Thus, no one can predict at present what the effects of the current recommendations will be, particularly when implemented in childhood. By implying that such nutritional strategies against chronic diseases of middle adulthood are necessary and should be applicable to the population at large, including growing children, health officials have shaken confidence in our Western diets and may have created a widespread fear of food. Strict adherence to low-fat, low-cholesterol diets in childhood may result in nutritional growth failure, while long-term benefits in reducing coronary heart disease may not be accomplished for the majority of the population who may not need marked dietary changes. Moderation is the theme for adequate nutrition in childhood. PMID- 1619210 TI - Adrenal medullary secretion with splanchnic stimulation in spinal cats. AB - This project was undertaken to determine whether previously observed adrenal medullary hyperactivity that developed following high spinal cord transection in the cat could be explained by increased sensitivity of the synapse between the splanchnic nerve and chromaffin cell. The splanchnic nerve was stimulated in acute (2-3 h; n = 7) or chronic (61-64 days; n = 7), spinally transected (T3) cats that were decerebrate and unanesthetized. Mean arterial blood pressure and adrenolumbar venous blood flow were significantly greater in the chronic animals. Stimulation (30 V; 1 ms pulses) was applied at 3 Hz and 30 Hz to deliver the same number of pulses within 3 min. Adrenal medullary secretion (ng/min) of epinephrine (EPI), norepinephrine (NE), dopamine, neuropeptide Y (NPY), [Met]enkephalin (ENK), and encrypted [Met]enkephalin was determined at baseline and in relation to both patterns of stimulation. With near threshold (3 Hz) stimulation, the following differences were observed between groups: (1) secretion of EPI, NPY, and ENK was significantly greater in the chronic than in the acute animals; and (2) preferential secretion of NE was elicited in the acute animals. These observations suggest that there may be some facilitation of the splanchnic nerve--chromaffin cell synapse that occurs over time following high thoracic spinal cord transection. However, it is likely that central, spinal mechanisms also contribute to adrenal medullary hyperactivity. PMID- 1619211 TI - Sites at which neuropeptide Y modulates parasympathetic control of heart rate in guinea pigs and rats. AB - Immunohistological evidence indicates that neuropeptide Y (NPY) is present in the cardiac innervation of numerous species. The present experiments determined if NPY influences in vivo parasympathetic control of heart rate in guinea pigs and rats by either pre- or postganglionic mechanisms or by an interaction at muscarinic receptors at the sino-atrial node. Urethane-anesthetized animals were prepared with arterial and venous catheters, and ECG leads. The cervical vagi were sectioned and propranolol was administered to minimize reflex changes in heart rate. Methacholine injection, carbachol injection, or electrical stimulation of the peripheral end of the vagus nerve was performed to activate the neuroeffector site, intracardiac ganglion cells, or preganglionic neurons, respectively. All three trials were performed before, during, and after NPY infusion. No differences in methacholine- or carbachol-induced bradycardia were observed between control and NPY groups in either species. NPY infusion inhibited vagal-mediated bradycardia in guinea pigs and in rats. However, NPY inhibited vagal-mediated bradycardia at a lower dose in guinea pigs (1 microgram/kg/min) than in rats (4 micrograms/kg/min). These data indicate that NPY modulates cardiac vagal preganglionic, but not postganglionic nerve function or neuroeffector sites at the sino-atrial node, in guinea pigs and rats. Furthermore, due to the different effective dosages, NPY may play a greater modulatory role in guinea pigs than in rats. PMID- 1619213 TI - Visualization of enteric and gallbladder ganglia with a vital fluorescent dye. AB - A method is described here for the vital staining of the nerve plexuses of the gastrointestinal tract with the fluorescent dye 4-(4-diethylaminostyryl) methylpyridinium iodide (4-Di-2-ASP). This dye stained nerve fibers in the myenteric and submucosal plexuses and in the intramural ganglia of the gallbladder. In addition to staining the ganglia, the dye clearly revealed the secondary and the fine tertiary fibers of the myenteric plexus. In the submucosal plexus thin fibers innervating the blood vessels were also stained. This method proved to be effective in tissues that are relatively thick and in which the visualization of the nerves is quite difficult without staining--the myenteric plexus of rat small intestine, guinea-pig gallbladder and human large intestine. The staining did not fade within at least 6-8 h, or after long exposure to bright light. Intracellular recordings from myenteric neurons in the guinea pig ileum showed that cellular properties were not significantly altered after incubation in the dye solution. 4-Di-2-ASP thus appears to be suitable for rapid vital staining of nerves in whole mount from many parts of the gastrointestinal tract. PMID- 1619212 TI - Viscero-sympathetic reflex responses to mechanical stimulation of pelvic viscera in the cat. AB - Viscero-sympathetic reflex responses to mechanical stimulation of urinary bladder and colon were studied in cutaneous vasoconstrictor (CVC) neurones supplying hairy skin, in muscle vasoconstrictor (MVC) neurones supplying skeletal muscle and in sudomotor (SM) neurones supplying the sweat glands of the central paw pad of the cat hindlimb. The cats were anaesthetized, paralysed and artificially ventilated. The vasoconstrictor activity was recorded from the axons of the postganglionic fibres that were isolated in filaments from the respective peripheral hindlimb nerves. The activity in the sudomotor neurones was monitored by recording the fast skin potential changes occurring on the surface of the central paw pad. Afferents from the urinary bladder and from the colon were stimulated by isotonic distension and isovolumetric contraction of the organs. Most CVC neurones with ongoing activity were inhibited by these stimuli; only a few CVC neurones were excited. The MVC and SM neurones were generally excited by the visceral stimuli, yet the size of the evoked skin potential changes was variable. The reflex responses elicited in the sympathetic outflow to the cat hindlimb by stimulation of visceral afferents from the pelvic organs are uniform with respect to the different types of afferent input system but differentiated with respect to the efferent output systems. Graded stimulation of the visceral afferents from the urinary bladder by isotonic pressure steps elicited graded reflex responses in CVC (threshold less than 30 mmHg) and MVC neurones (threshold less than 20 mmHg) and a graded increase of the arterial blood pressure (threshold less than 20 mmHg). These graded reflex responses are closely related to the quantitative activation of sacral afferent neurones with thin myelinated axons innervating the urinary bladder that are also responsible for eliciting the micturition reflex, but not to the quantitative activation of sacral afferent neurones with unmyelinated axons. The latter have thresholds of 40-50 mmHg intravesical pressure at which the size of the vesico-sympathetic reflexes in the vasoconstrictor neurones was about 50% of maximal size. This does not exclude the fact that activation of unmyelinated vesical afferents contributes to the vesico sympathetic reflexes. PMID- 1619214 TI - A study of catecholamine concentrations in selected renal segments of cats of different ages. AB - Renal concentrations of the catecholamine neurotransmitters norepinephrine (NE) and dopamine (DA) in 19 cats were measured by reverse-phase high pressure liquid chromatography (HPLC) with electrochemical detection. Animals of five different age groups (2-4, 6-8, 10-12 and 16-20 weeks and adult animals one year and older) were anesthetized and the kidneys were excised, sectioned into cortical, outer medullary and inner medullary segments, and processed for HPLC. There were no statistical differences in cortical NE concentrations between the 2-4 week and adult age groups, suggesting that peak noradrenergic nerve terminal density in the cortex is achieved at or before 2-4 weeks of age. NE concentration in the outer medulla and DA concentration in the cortex and outer medulla increased from the 2-4 to the 10-12 week age group but did not change significantly in the older animals. There were significant decreases in inner medullary NE and DA concentrations from the 10-12-week to the 16-20 week age group. The decrease in concentration of inner medullary catecholamines in the early postnatal period is consistent with the reported total loss of tyrosine hydroxylase- and dopamine beta hydroxylase-immunoreactive inner medullary nerve terminals at approximately 12 weeks of age. PMID- 1619217 TI - Foreign bodies. PMID- 1619215 TI - Deltamethrin residues in milk and tissues of lactating dairy cows. AB - Lactating dairy cows were fed deltamethrin (2 or 10 mg kg-1 feed) for 28 consecutive days and deltamethrin residues measured in milk and tissues. Deltamethrin residues were higher relative to dose administered. The order of relative concentrations of deltamethrin in tissues, measured 1, 4, and 9 days after the last dose was: renal fat greater than subcutaneous fat greater than forequarter muscle greater than hindquarter muscle greater than liver greater than kidney. Depletion of deltamethrin residues in milk was very rapid indicating the half-life of the insectide of about 1 day. Trace amounts of deltamethrin metabolites 3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (less than 0.0235 ppm) and 3-phenoxybenzoic acid (less than 0.034 ppm) were also detected in milk and tissues of treated cows. PMID- 1619216 TI - Pharmacokinetic profile and anticholinesterase properties of phenamiphos in male rats. AB - The pharmacokinetics and anticholinesterase properties of a single oral dose 6 mg/Kg of technical phenamiphos [ethyl 4-(methylthio)-m-tolyl isopropylphosphoramidate] were investigated in male rats. Animals were killed at each time intervals of 0.5, 1.0, 1.5, 3, 6, 12, 24, 48, and 72 hrs after dosing. The total recovered amount of phenamiphos from brain and plasma tissues reached high level at the first time interval and disappeared biexponentially from both tissues to low level at the end of the experiment. Brain tissue has a greater affinity to phenamiphos than plasma tissue. The half-life of the elimination of phenamiphos from brain and plasma were 100 and 212 hr corresponding to the rate constant values of 0.01 and 0.003 hr-1, respectively. Plasma AUC (area under the curve) value was 1239.81 micrograms hr/L, explaining there was no tendency for the compound to accumulate in the brain tissue (AUC = 774.38 micrograms hr/Kg) compared to the plasma. On the other hand, determination of cholinesterase activity showed that, phenamiphos inhibited the enzymes in both brain and plasma, where the depression of ChE activity was usually more marked in plasma than in brain. PMID- 1619218 TI - An assessment of oblique base wedge osteotomy stability in the first metatarsal using different modes of internal fixation. AB - The modified Juvara osteotomy is a classic oblique base wedge osteotomy of the first metatarsal and is often used to reduce hallux valgus deformity. However, complications attributed to osteotomy instability and currently available modes of osteosynthesis are common. The authors have developed a technique that enables them to quantitatively and objectively evaluate the stability of this osteotomy when various modes of internal fixation are used. Stability testing was performed on fresh, previously frozen human cadaveric specimens using engineering principles. Results indicate that there is no statistically significant difference in stability between crossed 0.062-inch Kirschner wire fixation and internal fixation using a single 3.5-mm. cancellous screw. The tests also indicate that both of these techniques are superior to two 2.7-mm. cortical screws for stability. PMID- 1619219 TI - Neurilemmoma of the posterior tibial nerve with an uncommon case presentation. AB - A neurilemoma presenting in the foot is uncommon. The tumor is a solitary benign type that does not require transection of the involved nerve. A clinical review with an uncommon presentation and brief history of a benign neurilemoma is presented, followed by a discussion using magnetic resonance imaging, ultrasonification, double contrast doppler, arteriograms and venograms to aid in a differential diagnosis. PMID- 1619220 TI - Peroneal tubercle osteochondroma. AB - Osteochondromas are common bone lesions; however, their occurrence in the calcaneus is rare. A discussion of this lesion along with an unusual case and related findings are presented. PMID- 1619221 TI - Ankle dislocation without fracture: an unusual case report. AB - Complete dislocation of the ankle joint without associated fracture is considered a rare injury. Few cases are reported in the literature. A case report is presented, and a review of the etiological factors and treatment principles are discussed. PMID- 1619222 TI - McBride's operation for hallux valgus can be used in patients older than 30 years. AB - Over a 10-year period, 46 feet with hallux valgus in 36 patients were treated with the McBride procedure. The median age was 35 years. At follow-up of 2 to 11 years after operation, a reduction in the hallux valgus angles, the intermetatarsal angles and the width of the forefeet was found. In patients older than 30 years there were significant reductions. In patients younger than 30 years, the reduction was not significant. The rate of problems with daily footwear was reduced from 36 of 46 feet to 13 of 38 feet. The authors noted few problems and a high rate of satisfied patients, despite the age. In 37 of 46 feet the overall result was found satisfactory by the patients. The authors find that McBride's operation can be used for hallux valgus, also in patients above 30 years, in spite of the generally accepted restriction to younger individuals. PMID- 1619223 TI - Gadopentetate-enhanced magnetic resonance imaging with fat saturation in the evaluation of Morton's neuroma. AB - Morton's neuromas, though usually diagnosed clinically, can occasionally be problematic. When required, imaging may be performed via ultrasound or computed tomography, though the former can be quite operator-dependent, and the latter exposes the patient to ionizing radiation. Magnetic resonance imaging can be very helpful in certain clinical situations. This case report demonstrates the usefulness of gadopentetate-enhanced magnetic resonance imaging with fat saturation in the evaluation of interdigital neuromas. PMID- 1619224 TI - Thorn-induced granuloma of the medial cuneiform. AB - A lytic lesion of the medial cuneiform of a 10-year-old boy was explored surgically, and a date palm thorn was identified. Histology revealed an aseptic granuloma. Even in the absence of a definite history of trauma, an organic foreign body lesion should be considered in the differential diagnosis of a lytic lesion of bone. PMID- 1619225 TI - Internal neurolysis. AB - One hundred seventy-eight patients diagnosed with a lower extremity nerve compression syndrome were treated conservatively using orthopedic, medical, and physical therapy modalities. Eighty-two per cent of these patients improved and recovered, and required no further care. Eighteen per cent of these patients did not recover or experience significant improvement in their sensory or motor loss. This chronic group was treated by internal neurolysis. Ninety-five per cent of this chronic group treated by internal neurolysis improved. Only 5% did not have significant prolonged relief or improvement and eventually required excision of a sensory peripheral nerve. Internal neurolysis may not be indicated in those patients who suffer from transient sensory paresthesias; conservative care and/or an external peripheral nerve decompression may suffice. Internal neurolysis is indicated in those patients who have constant sensory aberations or motor loss from a chronic peripheral nerve compression syndrome or any other nerve lesion that has not responded well to conservative care or to an external nerve decompression procedure. Internal neurolysis, in addition to conservative care regimes presented here, has been found to be effective in reversing heretofore thought to be irreversible pain syndromes in the lower extremity even when significant atrophy has already occurred. PMID- 1619226 TI - Fractures of the proximal phalanx of the hallux: the use of plates with displaced multifragment fractures. AB - Fractures of the proximal phalanx of the hallux are a common injury. Due to the important biomechanical function of the first ray, these injuries must be treated properly. Incorrectly treated, a fracture of the hallux can be debilitating. These injuries will be discussed, and several illustrative cases will be presented with the use of plate fixation. PMID- 1619227 TI - A unique osteochondral fracture of the first metatarsophalangeal joint. AB - Presented is a case report of an osteochondral fracture occurring at the base of the proximal phalanx of the hallux secondary to trauma. Initial radiographic and clinical examination did not reveal the diagnosis. However, prolonged symptoms of pain, swelling, and limitation of first metatarsophalangeal joint range of motion led to further radiographic evaluation, which confirmed a suspected diagnosis of an osteochondral fracture. This is regarded as a most interesting case by the authors, in light of the fact that review of the literature revealed a paucity of descriptions of osteochondral fracture of the first metatarsophalangeal joint. In addition, all of the previously described lesions have been localized to the first metatarsal head. A review of the literature failed to reveal any fractures occurring at the base of the proximal phalanx of the hallux. PMID- 1619228 TI - Asymptomatic naviculocuneiform synostosis with a ganglion cyst. AB - This is the report of a naviculocueniform synostosis in a patient whose primary symptoms were due to a ganglion cyst over the involved area. Only eight patients have been reported in any past literature with this particular condition. This is the first case to present with an overlying ganglion cyst. PMID- 1619229 TI - Smooth Kirschner (K) wire fixation of distal metaphyseal osteotomy bunionectomies: a 10-year retrospective survey. AB - The authors reviewed 500 distal metaphyseal osteotomy bunionectomies with smooth Kirschner (K)-wire fixation performed over a 10-year period. Postoperatively, the patients were allowed to ambulate with a forefoot compression bandage and a semirigid surgical shoe. The cases were evaluated radiographically for malunion, delayed union, nonunion, aseptic necrosis, bone callus formation, and final alignment. Soft tissue and bone infection, as well as pin irritation, were also evaluated. Computation of results demonstrated eight malunions, one delayed union, no nonunions, and two cases of aseptic necrosis. There were 52 cases (10.4%) that led to bone callus formation; 54 patients (10.8%) experienced pin irritation. A total of seven infections occurred (1.4%) that could possibly be attributed to the pin, of which four (0.8%) required incision and drainage. It was observed that certain procedures, such as the Laird osteotomy, decreased the effectiveness of the K-wire, while others, such as the Chevron osteotomy, resulted in the fewest complications. Bunionectomies performed bilaterally or with adjunct procedures, in contrast to isolated bunionectomies, were also found to decrease the effectiveness of the K-wire. Due to the minimal number of complications that were encountered and the high success rate that was attained, the authors conclude that utilization of smooth K-wire fixation for distal metaphyseal osteotomy bunionectomies remains a viable and effective treatment alternative. PMID- 1619230 TI - Intra-operative contamination of bone and cartilage during an Austin bunionectomy. AB - During an Austin bunionectomy the potential exists for the head of the metatarsal to leave the sterile field and become contaminated. The authors present a case in which this occurred, with a 20-month follow-up. Possible options for decontamination are reviewed. PMID- 1619231 TI - Wu's bunionectomy: a clinical analysis of 150 personal cases. AB - The author discusses his modification of the Mitchell distal metatarsal osteotomy/bunionectomy, in a study of 150 cases. He advocates a distal transverse first metatarsal osteotomy, with fixation using Herbert bone screws. Stepwise description of the surgical technique with evaluation of cases including complications is provided. PMID- 1619233 TI - Coralline hydroxyapatite bone graft substitutes: radiographic evaluation. AB - The authors discuss a recently described bone graft material substitute derived from sea corals. They briefly review its background leading to the potential for clinical use. Radiologic evaluation is provided, with attention directed to its characteristics, compared with other bone grafts. PMID- 1619232 TI - Osteochondroma: review of the literature and case report. AB - Osteochondroma is the most common bone tumor of the foot. The podiatric surgeon should have an organized protocol to diagnose and treat suspicious osseous lesions in order to prevent undertreatment of malignant lesions, or overtreatment of benign lesions. The presence of a solitary osteochondroma is not sufficient indication for surgical removal. Surgical removal is indicated if the tumor produces pain, has radiographic features of malignancy, or shows abnormal increase in size. This case involves an osteochondroma of the fifth digit that was treated by digital amputation. PMID- 1619234 TI - A comparison of Biofix rods to rigid internal fixation in the treatment of elective osteotomies in foot surgery. PMID- 1619235 TI - Prospects for control of cholera with oral vaccines. PMID- 1619236 TI - Village health care providers in Matlab, Bangladesh: a study of their knowledge in the management of childhood diarrhoea. AB - This study was conducted among village health care providers in Matlab, Bangladesh in 1987. The objectives were to assess their knowledge of childhood diarrhoea and methods of management. All types of health care providers considered diarrhoea as a major childhood disease and opined that treatment should be initiated in case of four or more loose motions a day. Slightly more than half of the allopaths were aware of the scientific causes of diarrhoea; homeopaths and traditional healers in large proportions related diarrhoeal diseases with certain types of food, and 'evil eyes'. Eighty per cent of the allopaths reported use of oral rehydration solution in treating watery diarrhoea against 20% of the others. Prescription of antibiotics in treating dysentery was higher among allopaths than others. Allopaths were also less restrictive regarding continuation of breastfeeding and intake of food during diarrhoea among children. PMID- 1619237 TI - Haemolysin and enterotoxin production by Aeromonas caviae isolated from diarrhoeal patients, fish and environment. AB - Beta-haemolytic activity was shown by 46 (63%) of the 73 Aeromonas caviae strains isolated from diverse sources, such as diarrhoeal stools, fish ulcers and water in titres of 16-64 HU/ml. Only 2 strains showed alpha-haemolytic activity and the remaining 27% of them were nonhaemolytic. Live cells and culture filtrates of 60.3% of the A. caviae isolates caused accumulation of fluid in rabbit gut loops in the initial set of experiments. Of the 46 strains showing beta-haemolytic activity only 34 gave positive ileal loop reactions in the initial experiments. One of the 2 strains showed alpha-haemolytic activity and 9 of the 20 nonhaemolytic strains also caused fluid accumulation in the same set of experiments. Those strains that showed beta-haemolytic activity caused significantly more (p less than 0.01) fluid outpouring than the alpha- or nonhaemolytic isolates regardless of their sources of origin. Twenty-nine (39.7%) strains that showed alpha-, beta-, and nonhaemolytic activity and caused little or no fluid accumulation in initial experiments did so after 1-3 consecutive passages through rabbit gut. The nontoxic strain showing alpha- and non haemolytic activity switched over to production of beta-haemolytic activity once their live cells gave positive loop reactions. However, on repeated subcultures or on preservation in the laboratory for 2-3 weeks, all of them reverted back to their original nontoxic haemolytic types, i.e. alpha- or nonhaemolytic activity. PMID- 1619238 TI - Knowledge, attitudes, and practices and their policy implications in childhood diarrhoea in Uganda. AB - A nationwide study of the knowledge, attitudes, and practices about childhood diarrhoea among health workers and mothers of children less than 5-years old was conducted in Uganda during 1987. We found that each child, on the average, has 6 episodes of diarrhoea in a year. While most parents (65%) continue with almost normal feeding practices during their children's diarrhoea, as is officially recommended, there are some foods that are traditionally withheld. The use of oral rehydration therapy in the form of a salt and sugar solution is very limited and needs to be promoted. Herbal treatment for diarrhoea is a widespread practice and needs to be studied further to ascertain its usefulness. Over 55% of mothers recognise poor hygiene as the most important cause of childhood diarrhoea. The general level of sanitation is not satisfactory and needs to be improved to achieve the widespread availability of safe water and adequate means of human waste disposal for all homes. The radio was found to be a potentially effective tool for health education, and the need to provide all health workers with continuing education about diarrhoea management was identified. PMID- 1619240 TI - A community-based intervention for childhood diarrhoea control. PMID- 1619239 TI - Evaluation of a DNA probe to identify enteroaggregative Escherichia coli from children with diarrhoea in Bangladesh. AB - Six hundred and seventy-five Escherichia coli isolates obtained from 225 diarrhoeal children less than five years of age were tested for adherence to HeLa cells and for hybridisation with DNA probes for genes conferring aggregative adherence (AggA), localised adherence (LA) and diffuse adherence (DA) to assess the usefulness of a recently developed DNA probe for AggA of enteroaggregative E. coli (EAggEC). The strains were further analysed with the DNA probes for heat- labile enterotoxin (LT), heat--stable enterotoxin (ST), Shiga--like toxins (SLT I and SLT II) and for enteroinvasiveness and adherent strains were all negative for these properties. The HeLa cell assay and DNA probe assays showed excellent agreement in identifying LA and DA positive isolates. However, significant disparities occurred in the case of AggA positive isolates, and the DNA probe failed to identify 31.9% (15 of 47) of the EAggEC identified by the HeLa cell adherence assay. The failure of the DNA probe to identify all the EAggEC indicated that there may be a high degree of genetic heterogeneity for the expression of AggA, and development of more DNA probes is necessary to detect all the possible genetic variants of EAggEC. PMID- 1619241 TI - STb producing Escherichia coli are rarely associated with infantile diarrhoea. PMID- 1619242 TI - Vibrio mimicus bacteraemia in a child. PMID- 1619243 TI - Enterotoxigenic Bacteroides fragilis: epidemiologic studies of its role as a human diarrhoeal pathogen. AB - Strains of Bacteroides fragilis which produce enterotoxin(s) (ETBF) have been associated with diarrhoeal diseases in young domestic animals and have also been isolated from humans with diarrhoea. We have determined epidemiologically that ETBF are significantly associated with diarrhoea in humans. We studied Apaches, primarily children, with diarrhoea attending an outpatient facility in Whiteriver, Arizona, from July 1986 through July, 1988. Stool cultures for isolation of ETBF and other diarrhoeal pathogens were taken from these persons as well as from age and time-matched control persons who did not have diarrhoea. ETBF were isolated significantly more often from persons with diarrhoea (12%) than from controls (6%), p = 0.03. Isolation was highest (20-24% of stool cultures positive) during the second and third years of life. The diarrhoeal syndrome associated with ETBF was non-specific, and most characteristic of a secretory, rather than inflammatory, type of diarrhoea. ETBF are significantly associated with acute diarrhoea in Apache children, and may be an important newly described cause of diarrhoea in humans. PMID- 1619244 TI - A nine-month old malnourished baby girl presenting with shigellosis, pneumonia and shock. PMID- 1619245 TI - Bibliography on diarrhoeal diseases. PMID- 1619246 TI - When siting works, Canada-style. AB - Hazardous waste management poses increasing problems for Canadian provinces and American states, given the vast quantities and types of wastes generated and the virtual inability to open new storage, treatment, or disposal facilities. The Canadian experience is very similar to the American one in many respects, except for the fact that three provinces (Alberta, Manitoba, and Quebec) have devised alternative approaches to siting that appear successful in moving beyond the political gridlock so common on this issue. In each of these cases, traditional, top-down approaches to siting have been eschewed in favor of a more comprehensive approach that includes extensive public participation, economic and social compensation packages, formal partnerships between public and private organizations, and direct links between siting proposals and other aspects of waste management, including waste reduction, recycling, and export/import control. PMID- 1619247 TI - The effects of tort reform on medical malpractice insurance markets: an empirical analysis. AB - I use statewide loss ratio data to assess empirically the manner in which tort reforms have affected relative prices and profitability, and underwriting risk in the medical malpractice insurance industry. The empirical evidence suggests that the imposition of statutory ceilings on recoveries both decreased risk and improved relative profitability. Reforms that codified the required standard of care appeared to have a beneficial effect on relative profitability in certain cases. PMID- 1619248 TI - Speech, privacy, and the power of the purse: lessons from the abortion "gag rule" case. PMID- 1619249 TI - Can consumer choice reward quality and economy? Towards a test of economic competition. PMID- 1619250 TI - Will Medicare beneficiaries switch physicians? A test of economic competition. AB - We assess the potential of increased economic competition by examining whether Medicare beneficiaries are willing to switch to physicians who agree to accept all services on assignment. Data come from a survey of Medicare beneficiaries conducted in November 1988. Our principal finding is that beneficiaries are not sensitive to price when making decisions about whether or not to switch physicians. Less than one-half of 1 percent of the sample had switched physicians for economic reasons in the year prior to the survey. Furthermore, willingness to switch was not correlated with ability to pay. We conclude that policies aimed at altering consumer demand may not be the most effective way to control Medicare costs. PMID- 1619251 TI - The media and the fate of the Medicare Catastrophic Extension Act. AB - We examine the Medicare Catastrophic Extension Act of 1988, which was repealed in 1989, finding a broad range of messages on this controversial legislation in the press. The time needed to craft compromise legislation in response to objections to the original bill was cut short by the impending deadline for payments by the elderly, January 1990. Outright repeal rather than modification was the result. Our study confirms earlier studies, which show that trends of opinion--in this case that of senior citizens over 65 years of age--could be forecast from mass media stories, and is consistent with the notion that legislation occurs in a climate shaped by the media. In addition to being a key conduit for passing information and pressures to the public and lawmakers, the media could also serve to indicate the impact of messages passed through other channels, such as direct mailings. PMID- 1619252 TI - HMOs for Medicaid: the road to financial independence is often poorly paved. AB - During the 1980s both the federal government and the private sector articulated policies to encourage the development and participation of health maintenance organizations (HMOs) in the Medicaid program. However, the policies, intended to save costs, limited the ability of new HMOs to achieve financial independence. New plans that emphasize Medicaid participation have few, if any, options on benefit design or in setting capitation rates. Relative to fee-for-service Medicaid programs, their costs to provide services may be quite high, as they have neither the buying power not the ability to impose discounts. As a consequence, plans must focus their financial planning efforts on targeting and attaining a stable enrollment base and on controlling the amount of services provided, tasks that are difficult for all HMOs. Achieving a stable enrollment base is particularly hard because Medicaid eligibles have few incentives to enroll and once enrolled often lose their Medicaid eligibility. Traditional HMOs control the amount of services provided through physician selection, financial incentives on physicians, and monitoring and utilization review. Lack of information and the difficulty inherent in attracting sufficient provider participation limit the first two strategies, so new plans often adopt organization structures that rely heavily on monitoring activities. Unfortunately, management information systems for HMOs are often the weakest link. We discuss the tasks and present data on financial planning, on putting financial plans into operation, and on monitoring progress toward financial independence for a set of ten demonstration projects sponsored by the Robert Wood Johnson Foundation. PMID- 1619253 TI - Decisions without consequences: cost control and access in state Medicaid programs. AB - States have implemented a number of strategies to provide services, pay providers, and control Medicaid spending. We test the effects of some differences in state Medicaid policies on program enrollees' access to and use of health care services. Logistic and OLS regression analyses of cross-sectional data indicate that these policies exert significant influences on enrollees' access to health services but have a weaker direct effect on their use of them. However, we find evidence that utilization is affected indirectly (through increased access) by state policy decisions. Somewhat surprisingly, Medicaid policies designed to contain costs by limiting utilization appear to affect neither access nor utilization. Medicaid enrollees have greater access to a private physician in states with higher physician reimbursement and additional Medicare insurance for their enrollees. Other nonpolicy variables with pronounced impacts on access to private office physicians include race and the availability of private insurance. PMID- 1619254 TI - Structure and meaning in medical sociology. AB - The point of all this, one made by others as well (e.g., Cook and Reichhardt 1979), is to emphasize the potential for a synergistic exchange between structuralists who do surveys and meaning-oriented workers who do qualitative work. The ways in which survey researchers come to understand the social worlds of people can and should be influenced by the ways in which people understand and interpret their own worlds. Correspondingly, our efforts to capture the social life of people through their eyes can be advanced by an understanding of the structures in which their lives are embedded and the effects of these structures. Each orientation benefits from drawing on the other. In this way, sociology is the ultimate beneficiary. I see nothing to be gained from intellectual antagonism and the distancing of one side from the other. I do not claim that there is more similarity and less difference between the two than meets the eye. The substance of interests and the styles of inquiry are really quite different. That's as it should be. Indeed, their differences permit each to give something to the other. Both should be nurtured and developed. However, in the training of new medical sociologists and in the research of old ones, we should have enough appreciation and knowledge of both orientations so that even if we are planted firmly in one, we are at least prepared to dip into the other. Those searching for structural effects and those searching for meaning are potentially natural partners, a relationship much superior to being unnatural antagonists. PMID- 1619255 TI - Widowhood and depression: explaining long-term gender differences in vulnerability. AB - Results from a 1986 national survey (N = 3,614) show that having ever been widowed is associated with current levels of depression and that this association is greater for men than women. Some of this apparent gender difference occurs because men have been widowed for a shorter average period of time than women and the effects of widowhood appear to lessen over time. Widowhood also is associated with different types and amounts of life strain for men and women. The results suggest that the primary mechanism linking widowhood to depression among women is financial strain. Among men, the more critical mechanisms seem to be strains associated with household management. When specific strains occur, they appear to have different effects on respondents who have ever been widowed and those who have not. Taken together, these results suggest that what appears on the surface to be a gender difference in vulnerability to the same life event turns out upon closer examination to occur because widowhood does not affect men and women in the same way. PMID- 1619256 TI - Parental role strains, salience of parental identity and gender differences in psychological distress. AB - Although past research indicates that women's higher levels of psychological distress can be accounted for by their greater exposure and vulnerability to role related stress, the social psychological factors contributing to female vulnerability have not been fully identified. This paper applies identity theory to the phenomenon of gender differences in distress among parents. From an identity perspective, I propose that salience of the parental identity in women's self-conceptions contributes to their vulnerability to parental role strains. Using 1988 survey data from a stratified random sample of married and divorced Indianapolis residents (N = 448), I find that gender differences in distress are explained by differences in exposure to parental role strains. Further analyses reveal, however, that salience of the parental identity contributes to both men's and women's vulnerability to parental role strains. These findings underscore the utility of identity theory for explaining psychological distress among women and men. PMID- 1619257 TI - Innovations in the measurement of life stress: crisis theory and the significance of event resolution. AB - Further progress in understanding the significance of stress for psychological well-being requires improved strategies for controlling both inter- and intra event variability across subjects studied. This paper reports on an innovation in stress measurement suggested by a proposition drawn from crisis theory that recognizes life events as representing opportunities as well as hazards. The crucial contingency is hypothesized to be the outcome of the event with respect to the extent of its resolution in emotional and practical terms. This paper examines the possibility that life events that have been resolved successfully may not contribute to individual stress. Data was gathered from community samples of physically limited individuals and of non-limited comparison subjects. Results from separate analyses of these data generally support this hypothesis. PMID- 1619258 TI - Predicting continued use of marijuana among adolescents: the relative influence of drug-specific and social context factors. AB - Most research on the determinants of adolescent drug use has focused on predictors of either initiation or current use. Little attention has been given to the determinants of continued use of drugs after initiation, even though some researchers have found that the consequences of continued use are more serious than those associated with experimental or occasional use. In this study, a longitudinal sample of 456 secondary and high school students who had already tried marijuana was used to examine the determinants of continued use of marijuana. Nearly 38 percent of those who had tried marijuana continued using, according to the definition operationalized in this study. Potential predictor measures were grouped in a drug-specific domain and a social context domain, and their effects on continued use, controlling for background characteristics, were examined in logistic regression models. Results showed that only the drug specific domain had a statistically significant effect on the likelihood of continued use. Students who felt that the adverse physical and psychological effects of marijuana were not very important reasons for discontinuing use and those who had gotten stoned during their experimental stage of use were the most likely to continue use after initiation. The results suggest that the perceived physical and psychological effects of the drug are more important determinants of continued use than are social factors or benefits related to use. Any relationships between social factors and continued use are mediated by the perceived effects and risks of the drug. PMID- 1619259 TI - Parental and peer characteristics as modifiers of the bond-behavior relationship: an elaboration of control theory. AB - Three bonds are at the core of Hirschi's control theory: attachment to parents, commitment to conventional activities, and belief in the conventional rules of society. Control theory does not include parental and peer attitudes and behaviors, variables that frequently are implicated in adolescent behavior. This study examines whether parental and peer behaviors and attitudes modify bond/behavior relationships. Adolescent cigarette smoking is the behavior of interest. Panel data from a probability sample of 685 adolescents shows that the relationship between attachment and adolescent smoking is modified by parental smoking; the relationship between commitment to conventional activities and adolescent smoking is modified by father's smoking; but the relationship between belief in conventional rules and adolescent smoking is not modified by parental or peer variables. We conclude that control theory needs to encompass parental behavior when considering adolescent smoking behavior. PMID- 1619260 TI - Trajectories of functional impairment in later life. AB - Functional impairment trajectories in late adulthood over a decade are characterized using the Longitudinal Retirement History Study (LRHS) data set. Non-linear patterns of age-related increase in impairment are documented with longitudinal data. Subsets of panelists from the initial large, nationally representative probability sample of employed males and unmarried employed females (N = 11,000) also exhibit differential non-linear trajectories of impairment by sex, income, and educational attainment. Concurrent analysis of the relationship over a decade among sex, SES, and functional impairment suggests that in health research, both sex and SES are broad proxy variables whose usefulness for understanding health outcomes and for policy analysis would be enhanced by the specification of components. PMID- 1619261 TI - Race differences in the effects of multiple roles on health: longitudinal evidence from a national sample of older men. AB - This paper examines race differences in the effects of social roles on physical health. Using data from the older men cohort of the National Longitudinal Surveys of Labor Market Experience, we examine the impact of employment, marriage, and being a supporter on health limitations and mortality. Employment has the most consistent health-protective effect, and the benefits of employment are more pronounced for Blacks than for Whites. Marriage affects health in conjunction with employment. These findings lend further support to the growing literature on the effects of roles on health. The results further illustrate the importance of ascribed statuses as structural determinants of the relationship between roles and health, highlighting the very real differences in the meanings and expectations of social roles for Blacks and Whites. PMID- 1619262 TI - Marital status and psychiatric disorders among blacks and whites. AB - This paper examines the association between marital status and psychiatric disorder for Blacks and explores the extent to which these patterns differ from those for Whites. Widowed and separated/divorced Black males and females have higher rates of disorder than the married; never-married Blacks do not have an elevated risk of psychiatric illness. The association between marital status and disorder for White males is similar and stronger than that observed for Blacks. For White women, the separated/divorced have a higher risk of disorder than the married, and unmarried White females have higher rates of the substance abuse disorders, but lower rates of the anxiety disorder than the married. Across all marital status groups, Black males and White males have higher rates of disorder (except for depression), than females. A complex pattern emerges when gender differences in the relative rates of disorder for unmarried Blacks compared to married Blacks are considered. Separated/divorced Black men, widowed Black women, and never-married Black men are worse off than their respective peers. Except for the separated/divorced, opposite patterns are evident for Whites. Directions for further research are outlined. PMID- 1619263 TI - Impact of a preventive job search intervention on the likelihood of depression among the unemployed. AB - Drawing on coping resources theory, we evaluate the impact of a job search intervention on depressive symptoms in a randomized field experiment at three follow-up periods covering two and one-half years. Baseline depressive symptoms, low social assertiveness, and financial hardship were identified as significant risk variables predicting depressive symptoms at follow-up. These variables then were used to identify high- and low-risk individuals in both experimental and control groups. Results indicated that the job search intervention had its primary impact on persons identified as being at higher risk for depression. Furthermore, the intervention had an impact on both the incidence and prevalence of more severe depressive symptoms among high-risk individuals. PMID- 1619264 TI - Bringing social worlds together: computers as catalysts for new interactions in health care organizations. AB - In this case study, computer systems are explored as catalysts for new interactions between departments in health care organizations. Hypotheses investigated changes in the extent to which members of different departments (1) exchange information and (2) understand each other's work following implementation of an integrated medical information system. Analyses showed that communication-based forms of involvement in implementation (communicating with systems personnel and trainers, communicating about new ways to use the system, and receiving support from supervisors for doing so) were overwhelmingly more important than either general participation or computer use in predicting increases in interdepartmental interaction. Changes in tasks and roles also led to new, informal, face-to-face contacts to support computer system use, as well as greater administrative control over the organization as a whole. In addition, results of interviews and observations over the two-year study period illustrate the importance of work group identification in predicting changes accompanying computerization. PMID- 1619265 TI - Gender differences in symptoms of depression among adolescents. AB - In this paper, we examine sources of gender differences in depressive symptoms among adolescents. Using data collected from a self-administered survey of 306 high school students, we examine differences in the impact of life events, psychosocial resources, and parent-child relationships on levels of psychological distress. Our results confirm a substantial gender difference in level of psychological distress. Moreover, analyses indicate that this gender difference may be due largely to higher levels of self-esteem among males and a tendency for adolescents to perceive their fathers to be overprotective. There is, however, also evidence that other psychosocial resources and parent-child relationships are implicated in this gender difference. We also present analyses to support our contention that parent-child relationships have important effects on the development of psychosocial resources of adolescents that, in turn, influence levels of depressive symptoms. PMID- 1619266 TI - Social structure, life stress and depressive symptoms in a high school-aged population. AB - Data from a randomly selected sample of 1,208 high school-aged adolescents were used to examine the means through which life stress is associated with depressive symptoms. Analyses focus on family structure, socioeconomic status, and gender as background risks which directly and indirectly influence symptoms, as well as vulnerability contexts that shape differential responsiveness to stressful experiences. Findings indicate (1) significant gender differences in aspects of stress exposure and in additive models of stress effects, but stresses and supports do not explain the significant gender difference in depressive symptoms; (2) girls in low education backgrounds have the highest levels of depressive symptoms; (3) there are no gender differences in vulnerability to stress; (4) children in single-parent families have higher symptom levels, effects explained by economic conditions and stress exposure--they are no more vulnerable than others to the depressing effects of these stresses; and (5) both boys and girls in low SES backgrounds are more vulnerable to a wide range of stresses and support deficits. PMID- 1619267 TI - Pseudo-outbreak of blastomycosis associated with contaminated bronchoscopes. PMID- 1619268 TI - Heliport-associated nosocomial mucormycoses. PMID- 1619269 TI - Of guides and guidelines. PMID- 1619270 TI - The agenda for change: development of the Joint Commission infection control indicators. PMID- 1619271 TI - Nosocomial human parvovirus B19 infection: lack of transmission from a chronically infected patient to hospital staff. AB - OBJECTIVE: To assess the potential for nosocomial spread of parvovirus B19 from a chronically infected patient. DESIGN: Employees exposed to the index case and control (unexposed) employees were evaluated by baseline and follow up parvovirus B19 serologies and hematologic assessments, and completed baseline and follow up epidemiologic questionnaires. SETTING: A chronically infected patient was hospitalized on a hematology ward in a research referral hospital for 3.5 weeks prior to a diagnosis of parvovirus B19 infection and the institution of isolation precautions. METHODS: Sera were screened for parvovirus B19 DNA (dot blot analysis), and IgG and IgM anti-B19 antibodies (capture immunoassay). Hematologic assessment included CBC, differential, and reticulocyte count. RESULTS: The index case had parvovirus B19 DNA at approximately 10(6) genome copies per ml of serum, elevated IgM and low levels of IgG B19 antibodies. Of the 21 exposed staff, 11 (52%) had IgG B19 antibodies and were immune; of the 8 unexposed staff, 6 (75%) had IgG B19 antibodies. No employees developed IgM B19 antibodies, B19 DNA, hematologic abnormalities, or clinical symptoms. CONCLUSIONS: In contrast to reports of documented nosocomial transmission of B19 parvovirus from patients in transient aplastic crisis, nosocomial transmission did not occur--even in the absence of isolation precautions--presumably from the lower level of B19 viremia in our chronically infected (rather than acutely infected) patient. PMID- 1619272 TI - Impact of a shielded safety syringe on needlestick injuries among healthcare workers. AB - OBJECTIVES: Evaluate the impact of a shielded 3 cc safety syringe on needlestick injuries among healthcare workers. DESIGN: Surveillance study. SETTING: Three medical centers. RESULTS: The total number of needlesticks from all sources rose from 134 during the baseline period to 140 during the study phase. However, the overall rate of needlesticks involving 3 cc syringes decreased from 14/100,000 inventory units to 2/100,000, and the frequency declined substantially at each of the participating medical centers. CONCLUSIONS: These results suggest that shielded syringes and related technology may offer potential for reducing the risk of needlestick injuries among hospital and other healthcare employees. This study should be viewed as a preliminary effort to assess the potential of shielded-syringe technology for reducing the risk of needlestick injuries among healthcare workers. The results are encouraging, but more clinical experience with this new device and longer follow up are essential to provide the data necessary for a definitive assessment of efficacy. PMID- 1619273 TI - FDA issues safety alert for hypodermic needles on secondary i.v. administration sets. PMID- 1619274 TI - In situ hybridization of bone matrix proteins in undecalcified adult rat bone sections. AB - We have developed a method for in situ hybridization of adult bone tissue utilizing undecalcified sections and have used it to histologically examine the mRNA expression of non-collagenous bone matrix proteins such as osteocalcin (bone Gla protein, BGP), matrix Gla protein (MGP), and osteopontin in adult rats. Expression was compared with that in bone tissues of newborn rats. In the adult bone tissue, osteocalcin mRNA was strongly expressed in periosteal and endosteal cuboidal osteoblasts but not in primary spongiosa near the growth plate. Osteopontin mRNA was strongly expressed in cells present on the bone resorption surface, osteocytes, and hypertrophic chondrocytes, but not in cuboidal osteoblasts on the formation surface. Osteopontin and osteocalcin mRNAs were expressed independently and the distribution of cells expressing osteopontin mRNA corresponded with acid phosphatase-positive mononuclear cells and osteoclasts. Expression of MGP mRNA was noted only in hypertrophic chondrocytes. In newborn rat bone tissues, expression of osteocalcin mRNA was much weaker than in adult rat bone tissues. These results clearly indicate the differential expression of mRNAs of non-collagenous bone matrix proteins in adult rat bone tissues. PMID- 1619275 TI - Procedures for specific detection of silver-stained nucleolar proteins on western blots. AB - Nucleolar organizer region (NOR)-silver staining of the chromosomes and nucleoli is a method that enables the detection of proteins associated with the ribosomal genes. We adapted the most commonly used cytochemical NOR-silver staining techniques to Western-blotted proteins of HeLa cells, mimicking the silver staining of cells in situ, and testing several parameters that may influence the in situ reaction. Two of these techniques, both one-step methods with colloidal developers, were standardized to obtain reproducible results. The specificity of NOR staining is documented by: (a) only a few bands are revealed among the many proteins detected by total proteins staining on gels or blots; two major groups of bands are found around 100 KD and 40 KD that could correspond at least in part to nucleolin and B23 nucleolar proteins; (b) the silver staining of bands was not the result of the high relative protein concentrations; and (c) the same number of NOR-silver-stained bands was observed across a large range of protein concentrations. The reaction appeared to be specific for a subset of nucleolar proteins, because the same bands were observed with the use of nucleolar, nuclear, or total cell protein extracts, and the silver grains observed in electron microscopy were clearly confined to the nucleolar fibrillar centers and dense fibrillar component. The efficiency of the reaction was not modified by any of the tested fixative pre-treatments except that involving methanol. The presented standardization of NOR-silver staining on Western blots allows the characterization of the Ag-NOR proteins and their specific regions responsible for silver staining of the nucleolus. PMID- 1619276 TI - Subcellular localization of xanthine oxidase in rat hepatocytes: high-resolution immunoelectron microscopic study combined with biochemical analysis. AB - Xanthine oxidase (XO), a molybdo-flavoprotein enzyme involved in purine degradation, was localized immunocytochemically in rat hepatocytes by high resolution immunoelectron microscopy. XO was isolated from rat liver and a 150 KD polypeptide was purified. Antibodies were raised in rabbits. Small pieces of fresh liver were quickly frozen by contact with a copper block pre-cooled with liquid helium and were freeze-substituted with either 2.5% OsO4 or 0.2% glutaraldehyde in acetone. They were then warmed and embedded in Epon-Araldite or Araldite 6005. Resin sections were treated by indirect immunostaining using anti rat liver XO antibody and protein A-gold. The labeling pattern was clearly over the cytosol and not on cell organelles. A few gold particles were found over the mitochondrial matrix, but not over the endoplasmic reticulum, Golgi apparatus, lysosomes, or peroxisomes, including their crystalloid core. These results are consistent with those of the biochemical assay of XO in this study. The significance of the occasional immunolabeling of the mitochondrial matrix remains obscure, since biochemical determinations in this study indicate no XO activity in the mitochondrial fraction. PMID- 1619277 TI - Distribution of type II collagen mRNA in Xenopus embryos visualized by whole mount in situ hybridization. AB - We have developed a whole-mount histochemical method to monitor the distribution of expressed genes within the intact, developing vertebrate embryo. Background problems that result from alkaline phosphatase- or horseradish peroxidase-based stains have been minimized, enabling both early and late stages of Xenopus embryogenesis to be monitored. The feasibility and utility of this non-isotopic method has been demonstrated by using a specific DNA probe to localize Xenopus laevis Type II collagen mRNA expression to areas surrounding the vacuoles of the notochord in Stage 30 embryos. Expression expands by Stage 41/42 to form a visually striking distribution pattern that includes a variety of chondrogenic tissues such as the vertebrae, otocysts, mandible, and periocular region. Although these experiments focused on expression of a structural gene, the high resolution and sensitivity of the method should allow it also to monitor expression of less abundant mRNA products of non-structural genes such as transcription factors, cytoplasmic regulators, and growth factors. In addition, this approach should be a successful tool to probe expression in normal and perturbed embryos not only of amphibians but also of other vertebrates, including avians and mammals. PMID- 1619278 TI - Identification of type I collagen-producing cells in human gastrointestinal carcinomas by non-radioactive in situ hybridization and immunoelectron microscopy. AB - Invasive growth of cancer cells induces desmoplastic reaction as one of the host reactions. It has been a matter of controversy whether stromal collagen is produced by cancer cells or stromal fibroblasts. In the present study, we investigated the cellular origin of Type I collagen in human gastrointestinal carcinomas by in situ hybridization and immunoelectron microscopy. In situ hybridization technique with digoxigenin-labeled RNA probes revealed that spindle shaped fibroblasts in the stromal area were abundantly positive for transcripts of pro alpha 1(I) collagen in intestinal-type adenocarcinoma. Gland-forming carcinoma cells were negative. In diffuse-type carcinoma of the stomach, spindle shaped or stellate fibroblasts were positive, whereas dissociated, oval carcinoma cells were negative. A precise determination of cell type was done by immunoelectron microscopy. Intracellular immunoreactivity for Type I collagen was observed in rough endoplasmic reticulum of fibroblasts (including myofibroblasts) in the stromal area. No definite reactivity was obtained in cancer cells by either in situ hybridization or immunoelectron microscopy. Our results indicated that stromal Type I collagen is produced by stromal fibroblasts, which are activated by cancer invasion. PMID- 1619279 TI - Distribution of manganese superoxide dismutase in rat stomach: application of Triton X-100 and suppression of endogenous streptavidin binding activity. AB - The distribution of rat manganese superoxide dismutase (Mn-SOD) was immunohistochemically investigated in the rat stomach with a specific polyclonal antibody and a labeled streptavidin-biotin immunoglobulin detection system in cryosections. Parietal cells in the stomach were intensely stained, whereas the other epithelial cells in the gastric gland and pit exhibited only slight staining. Rapid-freezing and freeze-substitution immunoelectron microscopy revealed that Mn-SOD in parietal cells was mainly localized in mitochondria. Therefore, the large amount of Mn-SOD in parietal cells is due to the abundant mitochondria, in which Mn-SOD is considered to play important roles in protecting the ion pump and the cell itself from superoxide insult. Application of Triton X 100, cryosectioning, and the streptavidin-biotin system are needed to distinctly visualize Mn-SOD with our antibody. Treatment of the cryosections with Triton X 100 enhanced not only the immunoreactivity but also the false-positive staining, which showed a similar distribution pattern to that of Mn-SOD and thus made it difficult to determine the localization. The most plausible cause of the false positive staining is thought to be endogenous biotin in the stomach, which survives paraformaldehyde fixation and is revealed by Triton X-100 treatment. Suppression of the endogenous streptavidin binding activity is important when cryosections, the streptavidin-biotin system, and Triton X-100 are employed. PMID- 1619281 TI - Differing cell surface distribution of human leukocyte antigen-DR molecules on epidermal Langerhans cells and eccrine duct cells. AB - Scanning electron microscopy (SEM) with immunogold labeling was employed to observe the undersurface of the human epidermis after it was split from dermal connective tissue, in an attempt to localize the molecules actually expressed on cell/tissue surfaces. We found that human leukocyte antigen-DR (HLA-DR) molecules were expressed on the surfaces of eccrine duct cells as well as those of epidermal Langerhans cells (LC) in normal skin. HLA-DR molecules, visualized by the deposition of gold particles, were distributed evenly on the LC surface but were present only along the interdigitating borders of the individual duct cells, thus producing a meshwork pattern on the duct surface. Transmission electron microscopy confirmed that the gold particles labeling cell surface HLA-DR molecules were seen only on the portions of duct cell membranes the interdigitated with neighboring duct cells. These findings suggest that the function of HLA-DR molecules may vary with their location and distribution. On the LC surface, the evenly distributed molecules seem to be well suited for promoting "accessory cell" functions. On duct cell surfaces, the HLA-DR molecules present along the intercellular spaces may be involved in trapping various peptide antigens that pass into the sweat gland filtrate and then are reabsorbed by the excretory duct, since these molecules have a highly permissive capacity for binding various peptides. PMID- 1619280 TI - Electron microscopic localization of the multicatalytic proteinase complex in rat liver and in cultured cells. AB - The multicatalytic proteinase (MCP) prosome or proteasome is a large multifunctional complex which is believed to play a major role in non-lysosomal pathways of intracellular protein degradation and has recently been implicated in antigen processing. In this study, affinity-purified antibodies against rat liver MCP were used to investigate the localization of the proteinase both in rat liver and in growing human L-132 cells in culture, using electron microscopic immunogold techniques. Quantitation of the MCP in different subcellular localizations by morphometric analysis of electron micrographs showed the proportion in the nucleus to be 17% for hepatocytes and 51% for L-132 cells, demonstrating differences in the distribution of MCP in different cell types. In hepatocytes, 14% of the total MCP was found associated with the endoplasmic reticulum. The remainder was localized in the cytoplasmic matrix. Immunofluorescence studies with L-132 cells also showed a reaction in nuclei and cytoplasm. The localization of MCP is consistent with its proposed multiple functions in protein turnover, in the production of peptides for antigen presentation, and in RNA processing. PMID- 1619282 TI - Demonstration of dopamine-immunoreactive cells in the gastrointestinal tract of gerbils (Meriones unguiculatus). AB - We investigated dopamine immunoreactivity in the small intestine of gerbils (Meriones unguiculatus), using a sensitive and selective antibody against glutaraldehyde-conjugated dopamine. Dopamine-immunoreactive cells were found within the mucosal epithelium along the entire extent of the small intestine. Labeled cells were regularly distributed in the upper half of the intestinal villi, basally attached to the basement membrane and always reaching as far as the epithelial surface. Dopamine-containing cells revealed a spindle-like shape, and both light and electron microscopic characteristics relate them to typical open-type gut endocrine cells. Thus, this current study directly identified dopamine as a probable secretory product in basal granulated cells of the small intestine. The functional significance of these cells is discussed in relation to the current view of dopaminergic actions in peripheral tissues. PMID- 1619283 TI - Histochemical studies of acid and alkaline phosphatases in rat tooth germs with undecalcified resin-embedded specimens. AB - A novel technique for the histochemical demonstration of acid phosphatase (AcPase) and alkaline phosphatase (AkPase) in hard tissues has been proposed. Fresh, unfixed, undecalcified samples of rat tooth germs and surrounding structures were embedded in LR Gold resin at -20 degrees C. Sections of 2 microns were taken and subsequently processed for enzyme histochemistry. AkPase reaction product appeared as strong linear staining outlining cell boundaries and was present in the enamel organ, dental pulp, and osteoblast cells. Tartrate resistant AcPase staining was seen exclusively in the osteoclasts of developing alveolar bone. Our results demonstrated that the use of unfixed, undecalcified LR Gold resin-embedded specimens for histochemistry is a novel technique which may be of value for certain studies when decalcification of specimens is undesirable. The technique appears to give good preservation of enzyme activity combined with the ability to prepare sections with excellent morphological detail. PMID- 1619284 TI - On intranucleolar chromatin and fibrillar centers in higher plants. PMID- 1619285 TI - Health and environment in Czechoslovakia. AB - The study summarizes basic information on environmental conditions and health status of the Czechoslovak population. It analyzes the relationships between health and environmental conditions, and Appendix brings the comprehensive results of relevant studies performed in Czechoslovakia. The analytic results suggest the quality of Czechoslovak ecology as unsatisfactory, which in some localities, e.g. North Bohemia coal fields, Prague, Ostrava, is next to critical, with heavy impact on the population's health. The Czechoslovak citizens are more prone to falling ill, die sooner than their peers in the majority of European and non-European countries. In addition to the specific effects of individual factors and life style also immunity, reproduction cycle, metabolic processes etc. become involved in the health-living conditions relationships. All these influences are responsible for high rates of morbidity due to the so-called civilization diseases. Inevitably, the only possible solution is to protect effectively human healthy by protecting his living conditions, i.e. environment and life style. PMID- 1619286 TI - Biological carrier improves passive protection of mice against Pseudomonas aeruginosa infection. AB - In a model experiment, the use of specific hyperimmune globulins (SHG) alone failed to protect mice against infection with homologous and heterologous P. aeruginosa serotypes. However, the therapeutic potential of SHG dramatically improved after its conjugation with A1(OH)3, used as a biological carrier. The binding of SHG to this carrier proved to be the most effective and stable combination in the treatment of acute pseudomonad infections in mice. PMID- 1619287 TI - Microbial causative agents of male urethritis. AB - The incidence of Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, Neisseria gonorrhoeae and Trichomonas vaginalis was studied in men with urethritis. Out of 150 examined men 48.7% had the positive isolation of U. urealyticum, 26.0% C. trachomatis, 22.7% N. gonorrhoeae, 18.7% M. hominis and in one (0.7%) patient T. vaginalis was found. None of the above mentioned microorganisms was detected in 24.7% of examined men. In 43.3% cases only one agent was isolated. In 23.3% of the men the combination of two agents, in 8.0% the combination of three and in 0.7% even the combination of four studied microorganisms was observed. C. trachomatis was most frequently observed in combination with N. gonorrhoeae (15 cases) and U. urealyticum (14 cases). M. hominis and U. urealyticum occurred simultaneously in 22 examined men.N.gonorrhoeae was most frequently found together with U. urealyticum (16 cases). Concerning the occurrence of other bacteria and yeasts, no significant difference was found between the groups positive and negative for the above mentioned microorganisms. PMID- 1619288 TI - Studies on immunomodulatory properties of isoniazid: V. Influence of isoniazid on secretion of interleukin-1. AB - Isoniazid in vitro decreased interleukin-1 production by glass-adherent cells from the blood of healthy donors. The previously described modulation of T cell activation by isoniazid seems to be independent of decreased interleukin-1 secretion. PMID- 1619289 TI - Reaction of macrophage disappearance as a method for the evaluation of cellular immunity in experimental plague. AB - The reaction of macrophage disappearance (RMD) was found to develop one day after the immunization of experimental animals with the antigen FIA of Y. pestis and to persist for 21 days, correlating with a pronounced protective effect of the above antigen over this period. There were differences between white mice and guinea pigs in the intensity of the RMD, particularly when immunization was carried out using an FIA preparation without prolonged action. These differences are thought to reflect varying degrees of immunity elicited by FIA immunization. It is recommended that the RMD be used to quantify cellular immunity to Y. pestis. PMID- 1619290 TI - A toxicological and epidemiological study on reproductive functions of male workers exposed to lead. AB - The reproductive ability of 24 men exposed to lead was observed and the same number of no-exposed men were taken as controls. The influential factors, such as age, smoking and drinking were controlled. The finding shows higher prevalence of congenital epilepsy and heart disease in the filial generation of workers exposed to lead and high rate of teratospermia in the exposed workers. Meanwhile hypospermia, as well as decreased lactate dehydrogenase-x(LDH-x) and succinodehydrogenase (SDH) in sperm were found in exposed group. PMID- 1619291 TI - Biological monitoring of deltamethrin in sprayers by HPLC method. AB - Using HPLC, the authors had investigated the three metabolites of deltamethrin (DM) in the urine of spraymen and one suicide, namely: dibromovinyl dimethylcyclopropane carboxylic acid (Br2A), 3-phenoxybenzyl-hydroxy-ethyl acetate (PHE) and 3-phenoxyl-benzoic acid (BA). Br2A was chosen as the biological monitoring parameter for DM exposed people, and the urine samples of one suicide and 11 farmers sprayed DM or DM plus methamidophos were examined for Br2A quantitatively which was detected in 8 of 11 sprayers and in the suicide case. PMID- 1619293 TI - Serosurveillance of susceptibility to rubella in a Mexican female group. AB - The susceptibility to rubella of a group of Mexican females of childbearing age was determined. Members of the group were selected based on the highest probability of having been exposed to the virus they were older than 15, and from a low socio-economic urban stratum. Anti-viral antibodies were determined by hemagglutination inhibition. Concentration was expressed as International Units of IgG anti-rubella hemagglutinin (IU). Antibody concentrations lower than 15.6 IU/ml were regarded as non-protective. A 16% susceptibility was found. PMID- 1619292 TI - Epidemiologic studies on human and feline toxoplasmosis. AB - Human serological profiles, and feline serological and fecal profiles were used to study the epidemiology of toxoplasmosis in Santa Clara County, California. The prevalence of human toxoplasmosis was determined to be 42.9% in a test population of 147 women. The prevalence of feline toxoplasmosis was indicated to be 34.8% based on serological analysis of 158 felines. Of 107 cats tested, 6.5% were shedding Toxoplasma gondii - like oocysts in their feces. Statistical analyses of questionnaire data indicated that the major infection sources for seropositive humans in this study were: (1) eating rare-medium cooked beef; (2) exposure to cats; and (3) working in an outside garden. Of these three sources, gardening represented the least risk. The data from questionnaires with reference to age, residence, and eating and toilet habits of owned felines were evaluated and found to show no significant statistical correlation with seropositivity. The infection sources for seropositive felines could not be determined. The plausible significance of feline-human interaction, human consumption of infected meat, and gardening habits is stressed. PMID- 1619294 TI - Empiric therapy of common bacterial infections in Saudi Arabia; a review. AB - The common infective conditions encountered at King Khalid Teaching Hospital, Riyadh, Saudi Arabia were described. These data were collected mostly during a period of 8 years between 1981 to 1988. These infections included brucellosis, cholecystitis, conjunctivitis, enteric fever, gastroenteritis, infective endocarditis, meningitis, otitis media, pneumonia, septicaemia, sorethroat, treponemal infections, urethritis, urinary tract infections, and vaginitis. A scheme for empiric chemotherapy has been suggested for these infections based on the sensitivity results obtained mostly from the microbiology laboratory at Teaching Hospital, Riyadh. This scheme of empiric therapy is offered as a guide only. It does not cover all possibilities and is not intended as a rigid dogma. Empiric therapy has also been suggested for some other infective conditions where sufficient data were not available from the Teaching Hospital. Empiric therapy should be started after relevant specimens are collected. Culture and sensitivity tests are invaluable in the management of patients with infectious diseases. As soon as sensitivities of the infecting organisms' are known, treatment should be adjusted accordingly. In some cases, Gram-staining is valuable to guide the initial therapy (eg. meningitis, pneumonia, and urethritis). Finally, close liaison between physicians and clinical microbiologists is mandatory for successful therapy. PMID- 1619295 TI - Semiautomatic photometric screening of urine samples for significant bacteriuria with high predictive values. AB - A simple method for screening urine specimens for significant gramnegative bacteriuria is presented, in which microtitration plates, a vertical-beam photometer used for reading ELISA and an inexpensive microcomputer are employed. The wells of the plate containing brain-heart infusion broth are inoculated with urine. Every hour turbidity is measured and the values are compared with the original ones. The whole examination is terminated in five hours. At the actual prevalence of 0.27, specificity is 0.97, the predictive value of a negative result is 0.97 and false positives 0.03. The method is used for rapid reporting to the ward, and for subsequent differentiated standard cultivation. PMID- 1619296 TI - Determination of Haemophilus influenzae and Haemophilus parainfluenzae susceptibility to ampicillin and other antibiotics. AB - A sample comprising 40 H. influenzae and 74 H. parainfluenzae strains was used to verify methods for determining susceptibility to antibiotics. Modified Levinthal agar proved to be suitable for the agar dilution and agar diffusion method, while brain heart infusion with the thermally released components of sheep blood (X and V factor) and lysed horse blood performed well in the dilution micromethod. The iodometric method served well for beta-lactamase production. A substantial proportion of strains was resistant to penicillin, erythromycin, roxitromycin and sulfamethoxazole. Ampicillin susceptibility was of crucial importance. Resistance was largely due to beta-lactamase production. Since there are ampicillin resistant strains which fail to produce beta-lactamase, it is necessary either to determine the MIC value or use a disk with 2 micrograms ampicillin. A disk containing 10 micrograms ampicillin may yield a false positive result. PMID- 1619297 TI - Toxicity of Bacillus thuringiensis against Damalinia ovis (Phthiraptera:Mallophaga). PMID- 1619298 TI - Isolation and characterization of four new strains of Bacillus sphaericus from central Nigeria highly toxic to mosquito larvae. PMID- 1619299 TI - The capacities of earthworms to heal wounds and to destroy allografts are modified by polychlorinated biphenyls (PCB). AB - Earthworms (Lumbricus terrestris) were maintained at 15 degrees C and exposed on filter paper to 10 micrograms/cm2 of the polychlorinated biphenyl (PCB) Aroclor 1254 for 5 days prior to surgical treatments which consisted of wounds, autografts, and allografts. At 1 day after surgery, we observed a higher percentage of healing defects and a significantly greater number of early signs of allograft rejection in exposed worms. Observations for 25 days post transplantation revealed no response to autografts, but an acceleration of the allograft rejection process in exposed earthworms. We postulate that Aroclor modified host coelomocytes and/or their interactions associated with antigen recognition and inflammation. PMID- 1619300 TI - A framework for automatic analysis of the dynamic behaviour of coronary angiograms. AB - A framework for coronary vessels analysis in digital subtracted angiograms is described. This method combines the motion estimation with the frame-to-frame structure detection in a natural way such that they act interactively. The first step consists of the extraction of the vessel centrelines in one image and their organization into meaningful constituents or branches of the coronary arterial tree. The motion is then estimated along the centrelines through a gradient based method. These motion estimates supply an initial positioning of an active contour model (or 'snake') in the next image. This model adapts itself by changing its shape to accurately fit onto the new centrelines. This process is then reiterated on the subsequent images to depict the dynamic behaviour of all the relevant branches. The main interests of this scheme are: (1) the active models operate locally so a fast detection of the vessels can be performed; (2) the centrelines extraction is fully guided by the confluence of the motion estimation and the contour model; (3) both morphological and kinetic features are provided on a quantitative basis. PMID- 1619301 TI - Computer methods in quantitation of cardiac wall parameters from two dimensional echocardiograms: a survey. AB - With increasing use of two-dimensional echocardiograms (2DE) for diagnosis [1, 2], efforts to computerize the process of quantification of cardiac parameters have increased. Visual processing of echocardiograms is time and labor intensive, and usually provides qualitative results with subjective variations [3]. In contrast, computer assisted methods are efficient and provide quantitative reproducible results. On the basis of the extent of computer usage, the 2DE processing methods are classified into three categories, namely, manual [9-30], interactive [32-49], and automatic methods [51-82]. This work is a structured survey of the published research on these three categories. PMID- 1619302 TI - Exercise echocardiography and single photon emission computed tomography in patients with left anterior descending coronary artery stenosis. AB - To compare the diagnostic value of exercise echocardiography and perfusion single photon emission computed tomography (SPECT) in the detection of the presence and the severity of coronary artery disease, we studied 21 patients with isolated stenosis of different degree of the left anterior descending artery. Both echocardiography and SPECT were performed in conjunction with the same symptom limited bicycle exercise test. Positivity of the test was based on the presence of exercise-induced wall motion abnormalities and transient perfusion defects, respectively. For both tests, an 'ischemic' score was derived, as index of extent and severity of myocardial ischemia. Coronary arteriography was evaluated by caliper. The agreement between exercise echocardiography and SPECT for the presence of coronary artery disease was 90%; the discordance was due to two patients with positive echocardiography and negative SPECT. A good correlation between ischemic wall motion and perfusion score indices was found (r = 0.78, p less than 0.0001. Moreover, the percent diameter stenosis was well correlated with both ischemic indices (r = 0.75, p less than 0.0001; r = 0.67, p less than 0.001, respectively). In patients with a positive test, the mean value of ischemic wall motion score index was higher in patients with a diameter stenosis greater than or equal to 70% than in patients with a diameter stenosis less than 70% (0.59 +/- 0.19 vs 0.29 +/- 0.12, p less than 0.01); a similar trend was found for ischemic perfusion score index (0.51 +/- 0.35 vs 0.27 +/- 0.12, ns).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619303 TI - Iopamidol in cardioangiography: a retrospective, multicenter study. Part I. Adult patients. AB - To evaluate the occurrence of complications during diagnostic or interventional catheterization a retrospective analysis of catheterization procedures in 12 Italian laboratories using the nonionic contrast medium (CM) iopamidol (370 mgI/ml) was performed. Data obtained on 26,219 patients greater than or equal to 14 years are presented. The overall complication rate was 1.89% (485/26,219). The overall mortality rate was 0.1% (27/26,219). Procedure related complications were 389 (1.48%) and CM related complications were 106 (0.4%). No death was attributed to CM. Ventricular fibrillation (VF) rate was 0.11% comparable to the low rate observed with nonionic CM in other studies and less than the rate observed in surveys concerning the use of ionic CM. Fifty-seven thrombotic events were recorded (0.22%), a rate comparable with other surveys with ionic and nonionic CM. The total complication rate (6.1%), the rates of coronary occlusion (1.34%), myocardial infarction (0.37%) and urgent coronary artery by-pass grafting (0.5%) in 1,348 coronary angioplasties were lower than those recorded in previous surveys. These data confirm a good tolerability and no increased risk of VF and thrombotic events with iopamidol in cardiac catheterization. PMID- 1619305 TI - Left ventricular opacification after peripheral venous injection of a modified albumin solution. AB - The usefulness of a modified albumin solution was assessed in 8 dogs after peripheral venous and inferior vena cava injections. The contrast agent is a mixed solution made of glucose, albumin and glycerin, with sonicated microbubble diameter of 5.0 +/- 2.3 microns. Multiple injections (8 ml each) of this contrast agent (total 80 injections) into peripheral vein and inferior cava were performed. The blood pressure from femoral artery was measured before, during and after injections. Two-dimensional echocardiograms were recorded in a modified long axis view on videotapes for play back analysis. The pulmonary transit time and left ventricular contrast persistent time was determined for each injection. The videodensity of the region of interest (ROI) at the center of right ventricle and left ventricle was measured. The background videodensity of both ventricles was evaluated. The videodensity over the ROI of both ventricles with peak contrast enhancement was measured in all frames for 3 consecutive cardiac cycles. The peak videodensity of right and left ventricle subtracting the background videodensity of each ventricles was further calculated respectively. The injections caused no change in blood pressure or heart rate. All injections produced right ventricular contrast echo. As much as 85% of peripheral venous and 82.5% of inferior vena cava injections resulted in left ventricular contrast which was 0.68 and 0.65 as bright as that produced in the right ventricle. Pulmonary transit time and left ventricle contrast persistent time of peripheral venous injection was 4.05 +/- 0.53 and 13.67 +/- 4.28 seconds respectively. No difference of these data (3.93 +/- 0.47 and 11.65 +/- 4.66 seconds) from those produced by inferior vena cava injections were noted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619304 TI - Iopamidol in cardioangiography: a retrospective, multicentre study. Part II. Paediatric patients. AB - To evaluate the complication rate in paediatric cardioangiography with the nonionic contrast medium iopamidol data on 8,166 procedures were retrospectively collected in 12 centres. The overall complication rate was 3.78% (309/8,166). 3.44% were related to the procedure, and 0.34% to the contrast medium. The mortality rate varied with age. It was higher in patients less than 2 months (0.38%) than in patients greater than 2 months-2 years (0.06%) and in patients older than 2 years (0.03%). The total complication rate was higher than the one observed in a similar retrospective analysis performed in adult patients (1.89%). This difference is probably due to higher risk conditions of the younger patients. However the contrast medium related complication rate (0.34% vs 0.4%) and the mortality rate (0.11% vs 0.1%) were comparable, confirming the good tolerability of iopamidol in cardiac catheterisation also in paediatric patients. PMID- 1619307 TI - [Two metalloproteinases produced from Pseudomonas aeruginosa, especially on the structure of active site and substrate specificity]. PMID- 1619306 TI - Coronary artery-cardiac chamber shunt: cineangiographic analysis. AB - Coronary artery-cardiac chamber shunts (CA-CC shunts) were observed in 101 out of 2267 consecutive patients (4.5%) receiving selective coronary angiography. In these patients, contrast medium injected into the coronary artery escaped directly into the cardiac chamber. CA-CC shunts were angiographically classified into the following two types. Type I: The endocardial layer was diffusely opacified, and contrast medium escaped into the cardiac chamber on systole (n = 83). Type II: Contrast medium escaped directly into the cardiac chamber via an undilated branch (n = 11). Type I and type II shunts were observed simultaneously in 7 patients. It is speculated that type I is a shunt via a persistent arterio sinusoidal vessel, while type II is a shunt via a persistent arterio-luminal vessel. Both types were observed frequently (24.9%) in hypertrophic cardiomyopathy. The degree of CA-CC shunts in hypertrophic cardiomyopathy was not influenced by the presence or absence of myocardial squeezing. CA-CC shunts are considered to be due to an abnormality in the coronary microcirculation of the myocardium. We describe the angiographic features of the two types of CA-CC shunt and discuss their pathophysiological significance. PMID- 1619308 TI - [Structural and functional aspects for the active site of glutathione synthetase]. PMID- 1619309 TI - [Topogenic sequences of integral membrane proteins for endoplasmic reticulum membranes]. PMID- 1619310 TI - [Immunohistochemical study on the expression of E-cadherin in normal tissues and squamous cell carcinomas of the uterine cervix]. AB - The expression of epithelial cadherin (E-cadherin) was immunohistochemically analyzed in normal tissues and squamous cell carcinomas of the uterine cervix and investigated clinicopathologically in relation to factors including the histological type, clinical stage (FIGO), tumor invasion and lymph node metastasis. The following results were obtained. (1) In normal cervix, E-cadherin was found at the cell to cell borders in both squamous and columnar epithelia, but not in stromal tissues. (2) In 38 patients with cervical cancer, 6 patients exhibited homogeneous staining of E-cadherin, while 32 showed heterogeneous expression, suggesting that cell to cell adhesion is not uniform in most cases. (3) In cases with large cell non-keratinizing squamous cell carcinoma invading to a depth exceeding 2/3 of the cervix, a significantly higher frequency of heterogeneous expression of E-cadherin was seen (p less than 0.05). (4) Patients who had cancer invasion exceeding 2/3 of the cervix with heterogeneous expression tended to have a high incidence of nodal metastasis. These results indicate that the expression of E-cadherin in cancer may be one of the factors most responsible for the process of invasion and metastasis in cervical cancer. PMID- 1619311 TI - [Significance of CA19-9 in mature cystic teratoma]. AB - We comparatively studied preoperative and postoperative serum CA19-9 levels in 170 mature cystic teratoma (MCT) cases. In MCT cases with positive serum CA19-9 levels, immunohistochemistry by means of an enzyme immunoassay was performed to determine in which tissues the high levels of serum CA19-9 had originated. 1. The preoperative serum CA19-9 level was high, 83.8 U/ml, against the low postoperative level of 32.9 U/ml. This suggested the possibility of CA19-9 being produced in the tumor of MCT. 2. There were 31 CA19-9 positive cases and CA19-9 was found in the bronchial gland tissue and surface epithelium in 9 and 4 cases, respectively, out of 23 cases with serum levels of more than 101U/ml. Out of 45 cases with normal CA19-9 levels, 4 had bronchial gland tissue and 3 had surface epithelium, both without CA19-9. Lewis system examination of those cases indicated Lewisa(-) and Lewisb(-) in all of them. 3. CA19-9 levels were higher in cystic fluid than in serum from MCT patients. This suggested two routes for the transfer into blood of tumor-tissue-produced CA19-9: 1) directly excreted in serum via surface epithelium; 2) retained in the ovarian cyst, then leaking into surrounding capillary vessels via the interstitium. 4. Clinically, CA19-9 is a marker necessary for examining MCT recurrence. PMID- 1619312 TI - [Relationship between sonographic endometrial images and endometrial histology during the secretory phase]. AB - Transvaginal sonographic endometrial images and endometrial biopsies were obtained during the luteal phase (L5-L10) from 31 patients with normal menstrual cycles. The Hyperechoic Endometrial Area (HEA) ratio was used as the index of sonographic endometrial dating, and 12 glandular and/or stromal parameters were used as the index of histological endometrial dating. The day of ovulation was determined with sequential transvaginal sonography. In 20 patients with a typical sonographic image, 80% of the HEA ratio was equal to L6 based on the histological endometrial dating, and 90% was equal to L9. These results suggested the efficacy of the sonographic endometrial dating. The remaining 11 patients with an atypical sonographic endometrial image were classified into 3 groups (hyperechoic, spotted and hypoechoic type). Two characteristic features, delayed glandular element and increased stromal cell density, were observed in the hyperechoic group. On the other hand, dissociation between glandular and stromal dating was observed in the spotted group. Hypoplastic glands and insufficient secretion were characteristic of the hypoechoic group. These results show that sonographic endometrial dating has clinical efficacy. This dating has enough coincidence with endometrial histology. Moreover, two advantages were recognized in the sonographic dating over the histological dating. One is the non-invasive examination, and the other is the real-time evaluation of the endometrium. PMID- 1619313 TI - [Recovery of ovarian function during postpartum period]. AB - To determine the effect of serum prolactin (PRL) on the recovery of ovarian function in the postpartum period, FSH, PRL, estradiol (E2), and 17 alpha-OH progesterone (17-P) levels were measured in postpartum women and the levels were compared with those in patients treated with bromocriptine. In addition, hMG was given for two days on the 10th and 30th postpartum days to the mothers treated with/without bromocriptine. On the 10th day, FSH levels tended to increase and the E2 and 17-P levels were significantly increased by bromocriptine treatment and these levels are compatible to those on the 30th day in the control group. Although no apparent change in E2 and 17-P levels was observed before and after hMG administration in the control, a significant increase in E2 on the 30th day and in 17-P on the 10th and 30th day was observed when the patients were treated with bromocriptine. These results suggest that high concentrations of PRL in the postpartum period suppressed the ovarian function not only due to the low gonadotropin secretion but also to the poor ovarian response to gonadotropin. 17 P seems to be preceded by estradiol secretion in the recovery of ovarian function during the postpartum period. PMID- 1619314 TI - [Assessment of diagnostic criterion of coldness in women with thermography]. AB - In this study 99 women were examined by thermography to diagnose coldness. We investigated the correlation between the surface temperature of various parts of the body and the atmospheric temperature during a day in 66 women with coldness and 33 without coldness by means of thermography. RESULTS: 1) Peripheral portions of the lower limbs giving readings lower than 26 degrees C in thermography were found in 67% of women with coldness and in 6% of those without coldness. 2) In the group of women with coldness, the mean surface temperatures in the peripheral portions of limbs were closely correlated with the mean atmospheric temperatures (r = 0.63, p less than 0.001), and the gradient of temperatures from the abdomen to the peripheral portions of limbs was greater at lower mean atmospheric temperatures. 3) A significantly large number (p less than 0.001) of women with coldness had a gradient of more than 6 degrees C observed compared with the other group. 4) The gradient was significantly larger (p less than 0.001) in women with coldness when the mean atmospheric temperature was under 15 degrees C than in women without coldness. CONCLUSION: When the gradient of the surface temperature from the abdomen to the peripheral portions of the limbs in thermography was more than 6 degrees C, we might be able to conclude that the subjects have coldness. PMID- 1619315 TI - [Molecular biological study on the overexpression of c-myc gene in uterine cervical carcinomas]. AB - The expression of mRNA for c-myc gene was investigated in 30 cases of human uterine cervical carcinoma by Northern blot hybridization, and c-myc gene amplification was also examined by Slot blot hybridization. Overexpression of c myc gene was detected in one (7.7%) of 13 cases of carcinoma in situ (stage 0), one (10.0%) of 10 stage I and 4 (57.1%) of 7 stage II uterine carcinoma, and c myc gene amplification was detected in 2 cases (6.7%) in which c-myc gene overexpression was also found. The patient whose c-myc mRNA level was more than 10 times as high as in normal uterine cervical tissue relapsed and died within 2 years after the first treatment. Our results suggest that the overexpression of c myc gene occurred more frequently in advanced than in early uterine cervical carcinoma and that it might be useful in prognosing cervical cancer. PMID- 1619316 TI - [Heterogeneity of CA 125 antigens released from human endometrial heterotopic epithelium and ovarian cancer]. AB - We purified CA125 antigen from the conditioned media (CM) of eutopic and heterotopic endometrial epithelial cells (EC) as well as ovarian cancer cell lines, SHIN-3 and HOC-I, to determine what molecular weight forms of CA125 antigen were identifiable. Treatment of the high-molecular-weight CA125 antigen with 6M urea yielded a much lower molecular mass peak. After purification by OC125 affinity column chromatography, samples were applied to 3 to 7% polyacrylamide gradient gel and analyzed by Western blot. A single band with a molecular weight (MW) of 200KDa was identified in eutopic EC materials. The CA125 polypeptide of the 110KDa molecule could be detected in all of the CM obtained from heterotopic EC, irrespective of the length of time in the cell culture. A MW of approximately 200 KDa was also observed in some heterotopic EC samples. On the other hand, although the multiple bands with a MW equal to orless than 200KDa were observed in the CM of two ovarian cancer cells, the CA125 polypeptide of 110KDa molecules could not be detected. This preliminary finding offers promise that the 110KDa molecule detection method may be a useful adjunct in the differential diagnosis of heterotopic EC and ovarian cancer. PMID- 1619317 TI - [Bone mineral content in premenopausal women treated with gonadotropin-releasing hormone analogue]. AB - To assess bone metabolism during treatment with gonadotropin-releasing hormone analogue (GnRHa), serum osteocalcin (BGP), alkaline phosphatase (ALP), parathyroid hormone (PTH), calcitonin (CT), calcium (Ca) and phosphorus (P) were determined before and after 6 months of GnRHa treatment in 15 premenopausal women with clinically diagnosed endometriosis. The bone mineral content (BMC) of the lumbar spine (L3) was measured by single energy quantitative computed tomography in 9 women, and in 6 of these 9 women microdensitometry was performed simultaneously during the treatment. BMC decreased significantly to 92.5 +/- 6.8% (mean +/- SD) of the pretreatment value after 6 months of treatment. On the other hand, microdensitometry revealed no significant change during treatment. Serum BGP and ALP were significantly higher after 6 months of treatment than before treatment, indicating an increase in bone formation. These data indicate that the GnRHa treatment induces an increase in bone turnover and a significant bone loss. PMID- 1619318 TI - [Quantitative evaluation of human placental aromatase during pregnancy by ELISA]. AB - To examine the relationship between the modulation of estrogen synthesis and placental maturation during pregnancy, we measured enzyme quantities and catalytic activities of aromatase in 78 normal human placentas (7-41 weeks gestation). The quantity was determined by ELISA with monoclonal antibodies specific to aromatase cytochrome P-450 (P-450arom). The activity was assessed by radioassay with [1 beta-3H] androstenedione. Intracellularly, the P-450arom concentration was twice as great in the microsomal fraction of term placentas (0.18 +/- 0.07%) as in the homogenate and mitochondrial fractions. Aromatase activity was also twice as great in the microsomal fraction as in the other fractions. The P-450arom concentration in microsomes increased linearly as pregnancy progressed (r = 0.759, p less than 0.001). The total P-450arom quantity in the placenta increased quadratically as pregnancy progressed (r = 0.891). Similar results were observed for aromatase activity. These results indicated that the increase in P-450arom was responsible for the increase in aromatase activity in normal human placenta. Therefore, in addition to the increase in placental weight and substrate derived from fetal adrenal during pregnancy, a further increase in P-450arom contributes to the marked increase in maternal estrogen production. PMID- 1619319 TI - [In vitro and in vivo effects of ginsenoside Rh2 on the proliferation of serous cystadenocarcinoma of the human ovary]. AB - Inhibition of human ovarian cancer cell proliferation in vitro and in vivo by Ginsenoside Rh2(Rh2) isolated from Red Ginseng was examined by using a cell line (HRA) derived from ascites of a patient with serous cystadenocarcinoma of the ovary. The HRA cell proliferation in vitro was inhibited in a dose-dependent manner with between 10 and 100 microM of Rh2. The uptake of radiolabeled precursors (3H-thymidine, 3H-uridine, and 3H-varine) by HRA cells was also inhibited in a dose-dependent manner with between 30 and 100 microM of Rh2. The growth of HRA cells transplanted into nude mice was not significantly inhibited by Rh2 alone. On the other hand, when cisplatin was administered together with 10 microM, 30 microM, or 50 microM Rh2, the growth of HRA cells was inhibited 31 and 35 days after tumor inoculation. Survival was also prolonged when cisplatin was administered with 10 microM and 30 microM Rh2. These results suggest that there is a synergistic effect between cisplatin and Rh2. PMID- 1619320 TI - [The clinical and pharmacokinetic evaluation of two-route chemotherapy with cisplatin and sodium thiosulfate in combination with angiotensin II]. AB - Thirty-six courses of chemotherapy with cisplatin (CDDP) and sodium thiosulfate (STS) were performed in 31 patients with gynecologic cancer 2 weeks after operation under the hypertensive condition induced by angiotensin II (AT-II). One hundred-fifty mg of CDDP/body was intraperitoneally administered while the usual systolic blood pressure was increased to 130-140% by AT-II. The hypertension was maintained for 15 minutes after finishing CDDP infusion, then 8g of STS was intravenously infused immediately after the cessation of AT-II. The urinary Pt level measured 15 minutes after finishing CDDP infusion was extremely low at 1.37 +/- 0.47 micrograms/ml, in spite of the significantly high levels of plasma total Pt (7.83 +/- 0.85 micrograms/ml) and filtrable Pt (4.02 +/- 0.55 micrograms/ml). This suggests that, during renal vasoconstriction induced by AT-II, the renal blood flow as well as renal uptake of CDDP was decreased. Plasma filtrable Pt levels were measured at 15, 30, 60 and 120 minutes after intraperitoneal administration of CDDP. At 15 and 30 minutes a significantly higher blood concentration was found than in the control group (p less than 0.05). However, CDDP-induced toxicities of the bone marrow, liver, kidney and alimentary tract were not increased. The extreme vasoconstriction in the kidneys and other organs induced by AT-II might have protected these organs from the toxicities of CDDP despite the fact that STS infusion was delayed by 15 minutes after CDDP infusion. STS infused immediately after the cessation of AT-II could neutralize the CDDP preventing the occurrence of toxicities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619321 TI - [Clinical significance of amniotic fluid interleukin-6--newly developed method, luminescence enzyme immunoassay]. PMID- 1619322 TI - [The effects of dipyridamole on proteinuria in preeclampsia]. PMID- 1619323 TI - [Psychosomatic approach for generalized anxiety disorders in climacterium]. PMID- 1619324 TI - [The 25th annual meeting of the Japanese Orthopaedic Association Musculoskeletal Tumor Society. July 17-18, 1992, Matsuyama, Japan. Abstracts]. PMID- 1619325 TI - [Diagnosis of adrenal gland diseases]. PMID- 1619326 TI - [Test procedures for the diagnosis of adrenal gland diseases]. PMID- 1619327 TI - [Imaging diagnosis of adrenal gland diseases]. PMID- 1619329 TI - [Drug enhancement of cortisol and glucocorticoid metabolism]. PMID- 1619328 TI - [Primary pigmented nodular adrenocortical diseases and hyporeninemic hypoaldosteronism]. PMID- 1619330 TI - [Diagnosis and therapy of adrenergic hypertension]. PMID- 1619331 TI - [Diagnosis and therapy of aldosterone-producing adrenal gland adenoma]. PMID- 1619332 TI - [Diagnosis and therapy of pheochromocytoma]. PMID- 1619333 TI - [Key points in diagnosis and therapy of adrenal gland diseases: discussion]. PMID- 1619334 TI - [Case of pulmonary valve stenosis due to tuberculous pericardio-pleural calcification]. PMID- 1619335 TI - [Case of pure progressive autonomic failure with sleep apnea syndrome]. PMID- 1619336 TI - [Case of arachnoid cyst complicated by multiple cystic disease]. PMID- 1619337 TI - [Autopsy case of palatal granulocytic sarcoma preceding the development of a tumor]. PMID- 1619338 TI - [Recent progress in the study of positron CT]. PMID- 1619339 TI - [Chronic fatigue syndrome]. PMID- 1619340 TI - [Case of glycogenosis III with marked fibrosis of the myocardium and cardiac failure]. PMID- 1619341 TI - Cysts of the mandible and maxilla. AB - Mandibular and maxillary cysts originate from elements of the teeth (odontogenic), or from epithelial remnants trapped in fusion lines during development (nonodontogenic). Both types can be clinically asymptomatic and must be treated surgically. The specific diagnosis of a jaw cyst and its recurrence depends upon the anatomical location, the radiographic appearance, and the pathological diagnosis. PMID- 1619342 TI - Dr Marion Souchon. Physician and artist. PMID- 1619343 TI - Chronic fatigue syndrome. AB - The chronic fatigue syndrome (CFS) is a poorly understood condition with nonspecific signs and symptoms, especially debilitating fatigue. Most patients can pinpoint the onset of their illness and usually describe a flu-like state. The search for an etiologic agent has focused on a number of viruses such as Epstein-Barr, enteroviruses, retroviruses, and human herpesvirus-6. Evidence supports persistent viral infection in a small percentage of CFS patients. Immunologic abnormalities do exist in CFS, which indicate the presence of immune activation in CFS patients. Although abnormal muscle biopsies have been found in some patients with CFS, strength and endurance appear normal, but perception of exertion may be abnormal. Patients with chronic fatigue have a high incidence of premorbid and concurrent psychiatric disorders, and on physical examination many often have reproducible tender points similar to fibromyalgic patients. Clinical evaluation should rule out other potential causes of fatigue, but elaborate diagnostic tests are seldom required. Presently, no specific treatment exists for CFS. A cognitive behavioral approach with or without the use of tricyclics has been advocated. Patients should be encouraged to maintain functional status and should not be discouraged from exercise. Several medications have been tried but with no definite clinical benefit. PMID- 1619345 TI - OSHA and the private practitioner. AB - The Occupational Safety and Health Act (OSHA) was passed by Congress over 20 years ago. Although the Act excludes workplaces with 10 employees or fewer, those employers affected are rarely knowledgeable about the Act provisions as they pertain to the specific workplace. Physicians' offices may have enough employees that compliance with OSHA is necessary. This brief article describes some highlights of regulations affecting health care workplaces. PMID- 1619344 TI - Lung cancer rates and risk factors in St Bernard Parish, Louisiana: an ecologic study. AB - The white population of St Bernard Parish, Louisiana displays excessive incidence and mortality rates for lung cancer. Examination of 14 years of case reports from the Louisiana Tumor Registry reveals an apparent cluster of high incidence in the rural portion of the parish. Based on a telephone survey, lifestyle risk factors for lung cancer (such as diet and tobacco consumption) appear to vary from one part of the parish to another. Specifically, cigarette smoking is more prevalent in the rural zones, particularly among males over the age of 45. In addition, the index of total vitamin A intake appears to be lowest in the rural zones where lung cancer incidence is highest. Occupational and environmental factors are also considered, but do not seem to vary geographically with lung cancer incidence. PMID- 1619346 TI - Physician practices and attitudes on HIV-related issues: a survey of LSMS primary care physicians. AB - In recent years there has been a dramatic increase in the number of HIV/AIDS patients in Louisiana. Despite this increase, there has been little investigation of physician perceptions of (1) the adequacy of treatment or (2) attitudes toward general HIV related issues. A study of LSMS primary care members (n = 470) indicated that most had not treated a HIV-infected or AIDS patient although the vast majority would readily do so. Reluctance was related to concern over scientific knowledge rather than any bias against such patients. Among physicians treating such patients, there was strong concern over availability of adequate hospitalization and home health care. PMID- 1619347 TI - 'Now, altogether'. PMID- 1619348 TI - Kentucky's bicentennial and a brief overview of 200 years of medical practice and the physician. 1. PMID- 1619349 TI - Sketch of the Kentucky State Medical Society. 1951. PMID- 1619350 TI - The truth about mammography. PMID- 1619351 TI - Nursing home restraints and legal liability. Merging the standard of care and industry practice. PMID- 1619352 TI - The impact of large medical malpractice awards on malpractice awardees. PMID- 1619353 TI - Therapeutic deception. A comparison of Halacha and American law. PMID- 1619355 TI - The diagnosis and treatment of TMD: Part 2. PMID- 1619354 TI - Wrongful death and the lost society of the unborn. PMID- 1619356 TI - Impacted teeth--an overview of treatment rationales. PMID- 1619357 TI - Bile acid solubility and precipitation in vitro and in vivo: the role of conjugation, pH, and Ca2+ ions. AB - The principles governing the in vitro solubility of the common natural conjugated and unconjugated bile acids and salts in relation to pH, micelle formation, and Ca2+ concentration are considered from a theoretical standpoint and then correlated first with experimental observations on model systems and second with the formation of precipitates containing bile acids in health and disease. In vitro, taurine-conjugated bile acids are soluble at strongly acidic pH; glycine conjugated bile acids are poorly soluble at moderately acidic pH; and many of the common, natural unconjugated bile acids are insoluble at neutral pH. For both glycine-conjugated and unconjugated bile acids, solubility rises exponentially, with increasing pH, until the concentration of the anion reaches the critical micellization concentration (CMC) when micelle formation occurs and solubility becomes practically unlimited. In vivo, in health, conjugated bile acids are present in micellar form in the biliary and intestinal tract. Unconjugated bile acids formed in the large intestine remain at low monomeric concentrations because of the acidic pH of the proximal colon, binding to bacteria, and absorption across the intestinal mucosa. In diseases in which proximal small intestinal content is abnormally acidic, precipitation of glycine-conjugated bile acids (in protonated form) occurs. Increased bacterial formation of unconjugated bile acids occurs with stasis in the biliary tract and small intestine; in the intestine, unconjugated bile acids precipitate in the protonated form. If the precipitates aggregate, an enterolith may be formed. In vitro, the calcium salts of taurine conjugates are highly water soluble, whereas the calcium salts of glycine conjugates and unconjugated bile acids possess limited aqueous solubility that is strongly influenced by bile acid structure. Precipitation occurs extremely slowly from supersaturated solutions of glycine-conjugated bile acids because of metastability, whereas super-saturated solutions of unconjugated bile acids rapidly form precipitates of the calcium salt. In systems containing Ca2+ ions and unconjugated bile acids, pH is important, since it is the key determinant of the anion concentration. For bile acids with relatively soluble calcium salts (or with a low CMC), the concentration of the anion will reach the CMC and micelles will form, thus precluding formation of the insoluble calcium salt. For bile acids, with relatively insoluble calcium salts (or with a high CMC), the effect of increasing pH is to cause the anion to reach the solubility product of the calcium salt before reaching the CMC so that precipitation of the calcium salt occurs instead of micelle formation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1619358 TI - Effect of dietary oils on lipid peroxidation and on antioxidant parameters of rat plasma and lipoprotein fractions. AB - In order to investigate the influence of fatty acid pattern and antioxidants other than vitamin E on lipid peroxidation and antioxidant levels of plasma very low density and low density lipoproteins (VLDL + LDL), the effects of three diets (equalized for vitamin E) containing soybean oil, olive oil, or an oleate-rich mixture of triglycerides (triolein) were studied in rats. A significantly lower concentration of thiobarbituric acid-reactive substances (TBA-RS) in plasma and lipoproteins was found after the olive oil diet (soybean oil, 3.7 +/- 0.4 nmol/ml; triolein, 2.1 +/- 0.5 nmol/ml; olive oil, 1.5 +/- 0.3 nmol/ml, in plasma) (soybean oil, 0.99 +/- 0.16 nmol/ml; triolein, 0.96 +/- 0.13 nmol/ml; olive oil, 0.38 +/- 0.12 nmol/ml, in the VLDL + LDL fraction). Furthermore, the results from in vitro copper-induced lipid peroxidation, expressed in terms of conjugated dienes, lipid hydroperoxides, and TBA-RS content, showed that VLDL + LDL particles from olive olive oil-fed rats were remarkably resistant to oxidative modification. The results suggest that the fatty acid unsaturation of dietary oils is not the only determining factor of the antioxidant capacity of lipoproteins in this animal model. The maximal protection observed after the olive oil diet may be explained by the presence of other unidentified antioxidants in addition to vitamin E, derived from oil intake. Therefore, the optimal balance between the content of unsaturated fatty acids and natural antioxidants in dietary oils appears to be of major importance. PMID- 1619359 TI - Solubility of calcium salts of unconjugated and conjugated natural bile acids. AB - The approximate solubility products of the calcium salts of ten unconjugated bile acids and several taurine conjugated bile acids were determined. The formation of micelles, gels, and/or precipitates in relation to Ca2+,Na+, and bile salt concentration was summarized by "phase maps." Because the ratio of Ca2+ to bile salt in the precipitates was ca. 1:2, and the activity of Ca2+ but not that of bile salt (BA-) could be measured, the ion product of aCa2+ [BA-]2 was calculated. The ion product (= Ksp) ranged over nine orders of magnitude and the solubility thus ranged over three orders of magnitude; its value depended on the number and orientation of the hydroxyl groups in the bile acid. Ion products (in units of 10(-9) mol/l)3 were as follows: cholic (3 alpha OH,7 alpha OH,12 alpha OH) 640; ursocholic (3 alpha OH,7 beta OH,12 alpha OH) 2300; hyocholic (3 alpha OH,6 alpha OH,7 alpha OH) 11; ursodeoxycholic (3 alpha OH,7 beta OH) 91; chenodeoxycholic (3 alpha OH,7 alpha OH) 10; deoxycholic (3 alpha OH,12 alpha OH) 1.5; 12-epideoxycholic (lagodeoxycholic, 3 alpha OH,12 beta OH) 2.2; hyodeoxycholic (3 alpha OH,6 alpha OH) 0.7; and lithocholic (3 alpha OH) 0.00005. The critical micellization temperature of the sodium salt of murideoxycholic acid (3 alpha OH,6 beta OH) was greater than 100 degrees C, and its Ca2+ salt was likely to be very insoluble. Taurine conjugates were much more soluble than their corresponding unconjugated derivatives: chenodeoxycholyltaurine, 384; deoxycholyltaurine, 117; and cholyltaurine, greater than 10,000. Calcium salts of unconjugated bile acids precipitated rapidly in contrast to those of glycine conjugates which were metastable for months. Thus, hepatic conjugation of bile acids with taurine or glycine not only enhances solubility at acidic pH, but also at Ca2+ ion concentrations present in bile and intestinal content. PMID- 1619360 TI - Bile acid synthesis. VI. Regulation of cholesterol 7 alpha-hydroxylase by taurocholate and mevalonate. AB - Taurocholate, a relatively hydrophobic bile salt, is a potent down-regulator of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase (C7 alpha H), the rate determining enzymes of the cholesterol and bile acid biosynthetic pathways, respectively. Inhibition of cholesterol synthesis with a bolus dose of mevinolin (lovastatin) a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, profoundly decreases the specific activity of cholesterol 7 alpha-hydroxylase and rate of bile acid synthesis in rats with complete biliary diversion. It is therefore conceivable that taurocholate may suppress cholesterol 7 alpha-hydroxylase primarily by down-regulating the activity of HMG-CoA reductase. To test this hypothesis, taurocholate was coinfused simultaneously to rats with chronic bile fistula with mevalonate (administered as mevalonolactone), an intermediate in the cholesterol biosynthetic pathway. Mevalonolactone was administered to provide a constant supply of newly synthesized cholesterol to cholesterol 7 alpha-hydroxylase, in order to overcome any inhibitory effect of taurocholate on HMG-Coa reductase. Infusions were started 72 h after biliary diversion, and carried out for an additional 48 h. Complete biliary diversion resulted in an increase in C7 alpha H specific activity (510%), protein mass (550%), steady-state mRNA levels (1430%), and transcriptional activities (330%) as compared to control rats with intact enterohepatic circulations. When rats with biliary diversion were infused intraduodenally with taurocholate, the specific activities of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase activities decreased by 75% (P less than 0.001) and 73% (P less than 0.001), respectively. Cholesterol 7 alpha-hydroxylase mass, mRNA, and transcriptional activity decreased after intraduodenal infusion of taurocholate to levels similar to those of rats with an intact enterohepatic circulation. The combination of constant infusion of mevalonate and taurocholate failed to reverse the inhibitory effects of taurocholate on cholesterol 7 alpha-hydroxylase activity, mRNA levels, and in vitro transcriptional rates. These data provide evidence that taurocholate represses cholesterol 7 alpha-hydroxylase at the level of gene transcription, and not via down-regulation of HMG-CoA reductase. Infusion of mevalonate alone to biliary diverted rats did not alter cholesterol 7 alpha-hydroxylase activity or mRNA levels, while leading to a 57% decrease in C7 alpha H gene transcription. This latter finding suggests that mevalonate or its metabolites may be capable of stabilizing C7 alpha H mRNA levels while down-regulating transcriptional activity. PMID- 1619361 TI - Glycerolipid synthesis in isolated adipocytes: substrate dependence and influence of norepinephrine. AB - Studies of fatty acid (FA) esterification by adipocytes have led to conflicting views with respect to how the process is regulated by norepinephrine (NE). It remains unclear whether NE directly modulates the pathway or whether its effects are indirect and reflect its well-known action to activate lipolysis. Changes in lipolysis can complicate estimation of esterification rates by altering both medium FA and the hydrolysis of newly formed FA esters. In this report, we describe an experimental approach that determined the effect of NE on FA esterification, amidst the complications introduced by activation of lipolysis. Esterification rates were estimated from the simultaneous incorporations (0.1-60 min) of [14C]glucose and [3H]oleate into diglyceride (DG), phospholipid (PL), and triglyceride (TG). Saturation kinetics of incorporation rates, with respect to FA, and more specifically to unbound or albumin-free FA (ubFA), were determined in both basal and NE-treated cells. To obtain true estimates of ester synthesis, incorporation rates were adjusted for label loss from breakdown of labeled esters. Our findings were: 1) In basal versus NE-treated cells, [3H]oleate, on its pathway to esterification, was diluted, respectively, by 2 and 50% of measured cell FA, and the diluting FA appeared derived from lipolysis. 2) Syntheses of PL, DG, and TG, estimated from incorporation of [14C]glucose, saturated at low ubFA. The Km for TG synthesis (0.06 microM) was within the physiological range of ubFA which meant that changes in plasma FA will modulate TG synthesis. PL synthesis, on the other hand (Km less than 0.01 microM), would be largely saturated under physiological conditions. 3) NE treatment increased the molar ratio of FA to albumin in the medium an average 8-fold and ubFA about 87-fold. In addition, NE accelerated hydrolysis of labeled PL and DG. Adjusting incorporation rates for these changes indicated that NE does not directly regulate glyceride synthesis. The assays described should allow estimation of glycerolipid synthesis under various metabolic or disease states and will distinguish direct effects from those reflecting changes in FA concentration or in hydrolysis of labeled FA esters. PMID- 1619362 TI - Genetic regulation of fatty acid synthetase expression in adipose tissue: overtranscription of the gene in genetically obese rats. AB - We have investigated the molecular mechanism of the overactivity of fatty acid synthetase (FAS) in adipose tissue from the genetically obese Zucker rat. Purified FAS from lean and obese rat adipose tissues displayed kinetics constants, molecular weight, and immunological properties that were identical. Western blot analysis revealed that FAS overactivity in obese versus lean rat adipose tissue was paralleled by a proportionate increase in FAS mass, i.e., 4 fold increase in suckling normoinsulinemic 16-day-old pups and 25-fold in weaned hyperinsulinemic 30-day-old rats. The determination of absolute FAS mass disclosed that FAS was quantitatively a major protein in obese rat adipose tissue accounting for 13% of cytosolic proteins versus 2% in lean rat at 30 days of age. FAS hyperabundance could be ascribed to an increased relative rate of FAS synthesis that was 6-fold higher in obese than in lean rat adipose tissue. Northern blot analysis demonstrated that FAS mRNA levels in obese rats were increased 4- and 14-fold over those of lean rats at 16 and 30 days of age, respectively, in very close proportion to the 3- and 15-fold increases in FAS gene transcription rates revealed by nuclear run-on assays. Southern analysis of genomic DNA did not allow for detecting amplification or any major structural changes in the FAS gene. It is concluded that FAS overactivity, shown here to be a life-long and general feature of all adipose tissue sites in the obese rat, arises primarily from FAS gene overtranscription. PMID- 1619363 TI - Two apolipoprotein B gene defects in a kindred with hypobetalipoproteinemia, one of which results in a truncated variant, apoB-61, in VLDL and LDL. AB - We report the presence of two distinct defects of the gene for apolipoprotein B, one resulting in a new truncated variant, apoB-61, in a kindred with familial hypobetalipoproteinemia (FHB). The proband (age 33) and a sister (age 36) are both compound heterozygotes with total cholesterol levels of 39 mg/dl and 50 mg/dl, and apoB levels of 1 mg/dl and 2 mg/dl in plasma, respectively. Both appear to be asymptomatic. The apoB-61 mutation, present in a total of five individuals and inherited from the proband's father, is a 37 bp deletion in exon 26 starting with nucleotide 8525. This results in an apoB of 2784 amino acids with 12 novel carboxy-terminal residues. The apoB-61 is present to a considerable degree, relative to apoB-100, in the proband's very low (VLDL) and low density (LDL) lipoprotein fractions. Both lipoprotein fractions have abnormal particle size distribution by electron microscopy. The LDL contain cuboidal particles. Total cholesterol, LDL cholesterol, and apoB levels in the family display three phenotypic patterns: normal, low, and extremely low. ApoB haplotyping indicates the presence of another defective apoB allele in a total of seven individuals. This allele leads to low levels of apoB-100. The second apoB gene-linked defect occurring together with the apoB-61 mutation explains the 3-phenotype pattern. The severe hypocholesterolemia seen in the proband and a sister result from the genetic compound state involving both alleles. This study shows that severe hypolipidemia in an individual heterozygous for a truncation in apoB is likely to involve a second genomic defect. PMID- 1619364 TI - Lecithin:cholesterol acyltransferase gene expression is regulated in a tissue selective manner by fibrates. AB - Plasma lipoprotein metabolism is influenced by several factors that may act by regulating the expression of proteins involved in lipoprotein metabolism, such as lecithin:cholesterol acyltransferase (LCAT). We determined the influence of several hormones and hypolipidemic drugs on hepatic LCAT gene expression and plasma LCAT activity. Liver LCAT mRNA levels were resistant to regulation by the hormones ethinylestradiol, L-thyroxine, hydrocortisone, or by the hypolipidemic drugs probucol, simvastatin, and nicotinic acid. In contrast, hepatic LCAT mRNA levels decreased to 67%, 64%, and 46% of the control levels after treatment with the fibric acid derivatives clofibrate, gemfibrozil, and fenofibrate, respectively. Fenofibrate lowered liver LCAT mRNA levels in a dose-dependent manner, which was paralleled by a decrease in plasma LCAT activity to 54% of the controls at a dose of 0.5% (w/w) in rat chow. The decrease in liver LCAT mRNA levels was maximal after 1 day, whereas the fall in plasma LCAT activity trailed by 2 days. Cessation of treatment with fenofibrate restored liver LCAT mRNA levels to control levels within 1 week. The transcription rate of the LCAT gene decreased by 25% in nuclei isolated from fenofibrate-treated rat liver, thereby indicating that hepatic LCAT gene expression is, at least partly, regulated at a transcriptional level. In contrast to the liver, brain and testis LCAT mRNA levels remained constant after treatment with fenofibrate, indicating that fibrates regulate LCAT gene expression in a tissue-selective manner. PMID- 1619365 TI - Reduction in the concentration and activity of plasma cholesteryl ester transfer protein by alcohol. AB - Plasma cholesteryl esters, synthesized within high density lipoproteins (HDL), may be transferred from HDL particles to other lipoproteins by plasma cholesteryl ester transfer protein (CETP). Alcohol consumption is associated with increased HDL cholesterol concentration and reduced plasma CETP activity. The alcohol induced decrease in CETP activity may be due to a low concentration of CETP in plasma or the inhibition of CETP by specific inhibitor proteins or alterations in the composition of plasma lipoproteins. The first two possibilities are studied further in this paper using data on 47 alcohol abusers and 31 control subjects. The activity of CETP was measured as the rate of cholesteryl ester transfer between radio-labeled low density lipoproteins and unlabeled HDL using an in vitro method independent of endogenous plasma lipoproteins. Plasma CETP concentration was determined by a Triton-based radioimmunoassay. The alcohol abusers consuming alcohol (on average 154 g/day) had 28% higher HDL cholesterol (P less than 0.01), 27% lower plasma CETP concentration (P less than 0.001), and 22% lower plasma CETP activity (P less than 0.001) than the controls. Plasma CETP concentration showed a negative correlation with HDL cholesterol among all the subjects (r = -0.317, P less than 0.01) but not among the alcohol abusers alone (r = -0.102, N. S.). During 2 weeks of alcohol withdrawal, plasma CETP concentration and activity of 8 subjects increased, whereas HDL cholesterol decreased by 42% (P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619367 TI - In vivo metabolism of a mutant apolipoprotein, apoA-IIowa, associated with hypoalphalipoproteinemia and hereditary systemic amyloidosis. AB - Apolipoprotein (apo) A-I is the major protein constituent of plasma high density lipoproteins (HDL). A kindred has been identified in which a glycine to arginine mutation at residue 26 in apoA-I is associated with hypoalphalipoproteinemia and hereditary systemic amyloidosis. We isolated the mutant protein, termed apoA IIowa, from the plasma of an affected subject and studied its in vivo metabolism compared to that of normal apoA-I in two heterozygous apoA-IIowa subjects and two normal controls. Normal and mutant apoA-I were radioiodinated with 131I and 125I, respectively, reassociated with autologous plasma lipoproteins, and simultaneously injected into all subjects. Kinetic analysis of the plasma radioactivity curves demonstrated that the mutant apoA-IIowa was rapidly cleared from plasma (mean fractional catabolic rate [FCR] 0.559 day-1) compared with normal apoA-I (mean FCR 0.244 day-1) in all four subjects. The FCR of normal apoA I was also substantially faster in the heterozygous apoA-IIowa subjects (mean FCR 0.281 days-1) than in the normal controls (mean FCR 0.203 days-1). Despite the rapid removal from plasma of apoA-IIowa, the cumulative urinary excretion of its associated radioactivity after 2 weeks (44%) of the injected dose) was substantially less than that associated with normal apoA-I (78% of injected dose), indicating extravascular sequestration of radiolabeled apoA IIowa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619366 TI - A missense (Asp250----Asn) mutation in the lipoprotein lipase gene in two unrelated families with familial lipoprotein lipase deficiency. AB - We have identified the molecular basis for familial lipoprotein lipase (LPL) deficiency in two unrelated families with the syndrome of familial hyperchylomicronemia. All 10 exons of the LPL gene were amplified from the two probands' genomic DNA by polymerase chain reaction. In family 1 of French descent, direct sequencing of the amplification products revealed that the patient was heterozygous for two missense mutations, Gly188----Glu (in exon 5) and Asp250----Asn (in exon 6). In family 2 of Italian descent, sequencing of multiple amplification products cloned in plasmids indicated that the patient was a compound heterozygote harboring two mutations, Arg243----His and Asp250----Asn, both in exon 6. Studies using polymerase chain reaction, restriction enzyme digestion (the Gly188----Glu mutation disrupts an Ava II site, the Arg243----His mutation, a Hha I site, and the Asp250----Asn mutation, a Taq I site), and allele specific oligonucleotide hybridization confirmed that the patients were indeed compound heterozygous for the respective mutations. LPL constructs carrying the three mutations were expressed individually in Cos cells. All three mutant LPLs were synthesized and secreted efficiently; one (Asp250----Asn) had minimal (approximately 5%) catalytic activity and the other two were totally inactive. The three mutations occurred in highly conserved regions of the LPL gene. The fact that the newly identified Asp250----Asn mutation produced an almost totally inactive LPL and the location of this residue with respect to the three dimensional structure of the highly homologous human pancreatic lipase suggest that Asp250 may be involved in a charge interaction with an alpha-helix in the amino terminal region of LPL. The occurrence of this mutation in two unrelated families of different ancestries (French and Italian) indicates either two independent mutational events affecting unrelated individuals or a common shared ancestral allele. Screening for the Asp250----Asn mutation should be included in future genetic epidemiology studies on LPL deficiency and familial combined hyperlipidemia. PMID- 1619369 TI - Really bad reimbursements at various stages (RBRVS). PMID- 1619368 TI - Correlations of plasma lipoproteins with LDL subfractions by particle size in men and women. AB - Nondenaturing gradient gel electrophoresis of plasma low density lipoprotein (LDL) has been used to identify major LDL subclasses that are influenced by genetic and other factors. In the present paper, this technique has been extended by measuring absorbance of lipid- or protein-stained gels as an index of concentration at intervals of 0.05 nm across the entire LDL particle size range (21.8-30 nm) in moderately overweight men (n = 115) and women (n = 78). When LDL absorbance levels were correlated with other lipoprotein variables, we found that the strengths of the correlations with each of triglycerides, apolipoprotein (apo) B, high density lipoprotein (HDL)2, and apoA-I achieve relative maximum values for two regions within the small LDL range (21-26 nm), one within LDL-IVB (22-23.2 nm) and a second within LDL-III (24.2-25.5 nm). We also found that the increase in LDL accompanying higher triglyceride levels occurs below 25.5 nm in men and between 24.5 and 26.5 nm in women, suggesting either that triglycerides are related to different LDL subclasses in men and women, or that particle sizes of metabolically homologous LDL subclasses may differ in men and women. As compared to analytic ultracentrifuge measurements, gradient gel measurements of LDL absorbance by the procedure described here provide greater resolution of LDL subclasses but less precision in estimating LDL levels. PMID- 1619370 TI - The forging of the Renaissance physician. Part III: The physicians and the period of rebirth. PMID- 1619371 TI - The forging of the Renaissance physician. Part IV: Physicians for all seasons. PMID- 1619372 TI - A national resource--a state treasure. PMID- 1619373 TI - Experience with cultured skin in a Georgia regional burn unit. PMID- 1619374 TI - "And there's more..."--Federal Trade Commission announces "new concern" with physician joint ventures. PMID- 1619375 TI - Ultrastructure of Staphylococcus aureus as revealed by microwave fixation. AB - The ultrastructure of the cell wall of Staphylococcus aureus was examined at electron microscopic level using new chemical fixation techniques during microwave irradiation and the results obtained were compared with those obtained by other conventional techniques. By using microwave fixation the concentric circular or zipper-like structure was observed in the cell wall. This structure was observed also with the spray-freeze-etch technique but not in thin section of the cells chemically fixed by conventional technique. For chemical fixative, glutaraldehyde is more advantageous than OsO4 as a concomitant fixative during microwave irradiation and postfixation by OsO4 is unnecessary and rather harmful for the preservation of the ultrastructure. The function of the observed structure is briefly discussed. PMID- 1619376 TI - "Pored-domes" of the fenestrated endotheliocyte of the glomerular and peritubular capillaries in the rodent kidney. AB - The fenestrated endotheliocyte of peritubular and glomerular capillaries in rat and mouse kidneys were observed with SEM and TEM. In the glomerular capillary, so called "pored-domes" were found not only at the fenestrated areolae but also at the nuclear region of the endotheliocyte. At the region between filtration surface and nuclear region, they accumulated to construct a sponge-like structure. The endotheliocyte of peritubular capillary also showed small "pored domes". The size and morphology of the pores in the "pored-domes" of glomerular and peritubular capillaries were similar to those of areolae fenestratae of the respective capillary. Based on the findings, we assumed that pored-domes and the sponge-like structure are the reservoir for the fenestrated area of the endotheliocyte to accommodate the rapid expansion of capillary lumen. PMID- 1619377 TI - Location of peptidoglycan and teichoic acid on the cell wall surface of Staphylococcus aureus as determined by immunoelectron microscopy. AB - Anti-peptidoglycan (PG) and anti-teichoic acid (TA) antibodies were prepared from sera of rabbits immunized with the cell wall fraction of Staphylococcus aureus Cowan I by the specific adsorption technique with purified teichoic acid or peptidoglycan. The anti-PG antibody recognized the trichloroacetic acid-treated walls (TCA wall) prepared from S. aureus, Bacillus subtilis, and Micrococcus luteus but did not react with teichoic acid or proteins extracted from the cell wall of Staphylococcus. The anti-TA antibody specifically reacted with cell wall teichoic acid of beta-type sugar configuration. The reaction sites of these antibodies on the cell wall of S. aureus Wood 46 were determined by immunoelectron microscopy using colloidal gold as a probe. The anti-TA antibody reacted mostly with the fibrous electron-dense mass on the cell surface. The reaction was also seen on the inner surface of the cell wall. The anti-PG antibody reacted with the fibrous structures and also directly on the cell wall surface. The distribution of the probes on the cell wall surface examined with the scanning electron microscope showed that there was no localized distribution in respect to the cell division. We knew from these observations that the external surface of the cell wall of Staphylococcus is covered with the fibrous mass which consists mostly of teichoic acid but partially of peptidoglycan. PMID- 1619378 TI - Preserving the original architecture of elastin components in the formic acid digested aorta by an alternative procedure for scanning electron microscopy. AB - The present study examined procedures of specimen preparation for observing elastin components in the formic acid-digested tissue by scanning electron microscopy (SEM). The rat thoracic aorta fixed in 4% paraformaldehyde was treated with 90% formic acid for 85-96 hr at 45 degrees C and processed in two different ways: 1) the tissues were freeze-dried directly from water and 2) they were treated with tannic acid and osmium followed by critical point drying. The former procedure caused marked deformation of elastin components, while the latter preserved them well in shape and arrangement. Thus, the three-dimensional organization and ultrastructure of the elastin components were precisely demonstrated in this study. PMID- 1619380 TI - Genetic polymorphisms in drug metabolism. PMID- 1619379 TI - A support film of plasma-polymerized naphthalene for electron microscopy: method of preparation and application. AB - Methods of preparing of a new support film by plasma polymerization in a glow discharge, and its application were described. The recently developed plasma polymerization replica technique was used to prepare ultrathin films from naphthalene monomer gas on the surface of a newly cleaved sodium chloride crystal or on cover glass. The film was floated off on water or hydrofluoric acid solution to free it from the base. The plasma-polymerized naphthalene support film (PNS) prepared in this way was shown to have excellent properties by its application to negative staining of virus antigen particles and by the observation of whole ultrathin sections of animal tissue mounted on a 2 x 1 mm single slot grid. Features of the new support film are (1) its ease of preparation as a clean, very thin film of less than 10 nm, (2) its amorphous texture and high transparency to electrons, (3) its mechanical strength, resistance to heat and chemicals, and electron bombardment, and (4) its smooth and slightly hydrophilic surface. The PNS would be useful for both routine and high-resolution electron microscopy. PMID- 1619381 TI - Aplastic anaemia: pathogenetic mechanisms and treatment with special reference to immunomodulation. AB - Aplastic anaemia (AA) has been defined as a syndrome in which the presence of pancytopenia is accompanied by marrow hypocellularity. Ample laboratory data and clinical observations continue to make immune mediation of bone-marrow failure an attractive hypothesis. Recent progress in the practice of bone-marrow transplantation has led to a survival rate of approximately 80% in the best cases, but such a treatment is only amenable in young patients (less than 45-50 years) with HLA-identical bone-marrow donors. Anti-lymphocyte and thymocyte globulin treatment has been surprisingly effective for AA, resulting in transfusion independence in 40-80% of patients. The mechanism of action is unknown, although effects on immunosuppression appear to be the most likely candidates. Long-term results for patients receiving cyclosporin A treatment will soon be available, and preliminary data show an effect similar to that of antithymocyte globulin. In contrast to successful bone-marrow transplantation, improvement following immunomodulation leaves quantitative abnormalities in all haematopoietic cell lines, and patients are prone to develop clonal (malignant) disease. PMID- 1619382 TI - A 3-month double-blind cross-over study of the effect of benazepril and hydrochlorothiazide on functional class in symptomatic mild heart failure. AB - The non-sulfhydryl selective angiotensin-converting enzyme inhibitor benazepril (20 mg daily) was compared with hydrochlorothiazide (50 mg daily) in post infarction (6-24 months) patients with symptomatic (NYHA functional class 2) mild heart failure. No concomitant drug therapy was given. The study had a double blind cross-over design with 3-month treatment periods. Both drugs were well tolerated, and both caused a similar reduction in systolic blood pressure. Heart rate was higher with the diuretic. Benazepril improved the NYHA functional class in 17 out of 29 (59%) patients, whereas one patient improved with hydrochlorothiazide (P = 0.0004). With regard to global efficacy score, benazepril was also superior. Thus, angiotensin-converting enzyme inhibitors may be superior to diuretics as first-choice therapy in symptomatic mild heart failure. PMID- 1619383 TI - Impaired erythrocyte fluidity during treatment of renal anaemia with erythropoietin. AB - Seventeen haemodialysis patients with renal anaemia were treated with recombinant human erythropoietin (rhEPO) and observed for 30 weeks. The viscosity of whole blood and plasma, the erythrocyte aggregation tendency, and the erythrocyte deformability, measured as fluidity, were analysed every second week. All patients responded with increasing haematocrit and whole-blood viscosity. The plasma viscosity and the erythrocyte aggregation tendency were already increased before the start of treatment, and remained unchanged during treatment. The basal erythrocyte fluidity tended to be impaired, although not significantly so. During treatment, significant impairment of fluidity was observed at the beginning of the treatment period. After 24 weeks the fluidity started to increase, and it later reached values observed before the start of treatment. Hence, the quality of the erythrocytes formed during the corrective phase of rhEPO treatment differs in some respects from that of cells formed at a normal production rate. The impaired fluidity might have important implications for the flow resistance in small vessels, and contribute to the development or aggravation of hypertension that is often seen during rhEPO treatment. PMID- 1619384 TI - Suppression of autoantibodies to factor VIII and correction of factor VIII deficiency with a combined steroid-cyclophosphamide-porcine factor VIII treatment in a patient with rheumatoid arthritis. AB - The presence of autoantibodies against factor VIII is an unusual but serious complication in rheumatoid arthritis. We describe the case of a patient who developed this kind of complication, with spontaneous bleeding and marked changes in the haematological parameters, that was unsuccessfully treated with a high dose of intravenous gammaglobulin. Subsequently, combined therapy with porcine factor VIII concentrate, cyclophosphamide and steroids led to the disappearance of the anti-factor VIII autoantibodies. PMID- 1619385 TI - Simultaneous occurrence of polymyalgia rheumatica in a married couple. AB - The case of a married couple who simultaneously developed polymyalgia rheumatica is presented. Both patients responded to steroid treatment, and when the steroid dose was gradually reduced both patients relapsed. The aetiology and pathogenesis of polymyalgia rheumatica remain unclear; familial aggregation indicates the involvement of genetic factors, whereas conjugal aggregation indicates infectious/environmental agents. In previous reports of polymyalgia rheumatica in married couples, the onset of symptoms in the two patients has usually been separated by a long chronological interval. It is concluded that the present report of simultaneous development of polymyalgia rheumatica in a married couple lends further support to an environmental or contagious aetiology. PMID- 1619386 TI - Familial hypercholesterolaemia and LDL receptor mutations. AB - Inherited defects in the gene for the low density lipoprotein (LDL)-receptor give rise to familial hypercholesterolaemia (FH), a disorder in which defective catabolism of LDL causes a marked increase in its concentration in plasma. As a result, there is excessive deposition of cholesterol in the arterial wall leading to accelerated atherosclerosis and premature coronary heart disease in most patients, although there are differences in its severity. Many different mutations have been found in the LDL receptor genes of FH patients, and although this heterogeneity has provided information about the relationship between structure and function in different domains of the protein, it makes simple DNA based diagnosis of the disease impossible. When sufficient groups of patients with defined mutations are available it will be possible to determine the relative importance of any particular mutation compared with other genetic or environmental factors in relation to the severity of their symptoms or their response to treatment. PMID- 1619387 TI - Apolipoprotein B gene mutations affecting cholesterol levels. AB - In the past 5 years, many different mutations in the apolipoprotein (apo) B gene have been described that affect plasma cholesterol levels. More than 20 different mutations in the apoB gene have been shown to cause familial hypobetalipoproteinaemia, a condition characterized by abnormally low plasma concentrations of apoB and LDL cholesterol. Almost all of the mutations are nonsense or frameshift mutations that interfere with the translation of a full length apoB100 molecule. Many, but not all, of these apoB gene mutations result in the synthesis of a truncated species of apoB that can be detected within the plasma lipoproteins. Familial hypobetalipoproteinaemia heterozygotes are almost always asymptomatic and have LDL cholesterol levels about one-quarter to one third of those of unaffected family members. Several homozygotes and compound heterozygotes for familial hypobetalipoproteinaemia have been described. In these individuals, the LDL cholesterol levels are extremely low, usually less than 5 or 10 mg dl-1, and the clinical phenotype is variable, ranging from completely asymptomatic to severe problems related to intestinal fat malabsorption. One missense mutation in the apoB gene (an Arg----Gln substitution at apoB amino acid 3500) is associated with very poor binding of apoB100 to the cellular LDL receptor. This syndrome has been designated familial defective apolipoprotein B (FDB). The amino-acid substitution at residue 3500 delays the clearance of LDL from the plasma and results in hypercholesterolaemia. In some Western populations, the frequency of FDB heterozygotes appears to be as high as 1 in 500 individuals. PMID- 1619388 TI - The role of apolipoprotein E genetic variants in lipoprotein disorders. AB - Apolipoprotein E plays a central role in lipoprotein metabolism by serving as a ligand for the binding of lipoproteins to lipoprotein receptors. Both common and rare variants of apoE have been described. The common variants apoE2 and apoE4 have a significant impact on interindividual variation of lipid and lipoprotein levels in normal subjects. The common variant apoE2 and more than half a dozen rare variants are defective in binding to the low-density lipoprotein (LDL) receptor, and all are causally associated with the lipid disorder type III hyperlipoproteinaemia (HLP). The mode of inheritance of the disorder can be either dominant or recessive, depending on the particular mutation(s) in apoE, although the mechanisms involved are not fully understood. The common variant apoE4 and other rare variants have been reported to be associated with a variety of other lipoprotein disorders, but a causal link has not been established. PMID- 1619390 TI - Hypertriglyceridaemia due to genetic defects in lipoprotein lipase and apolipoprotein C-II. AB - Hypertriglyceridaemia, as defined by fasting triglyceride levels of greater than 2.8 mmol l-1, is a prevalent dyslipoproteinaemia in our population. The underlying pathophysiological mechanisms that result in elevations of plasma triglycerides are heterogeneous and, in most cases, incompletely understood. However, in a subset of patients presenting with this lipid disorder, the biochemical and genetic defects that lead to hypertriglyceridaemia have been well characterized. These individuals present with the familial chylomicronaemia syndrome, a rare genetic disorder that is inherited as an autosomal recessive trait, and is characterized by severe fasting hypertriglyceridaemia, massive accumulations of chylomicrons in plasma, and recurrent bouts of pancreatitis. The two major causes of the familial chylomicronaemia syndrome are a deficiency of the enzyme, lipoprotein lipase (LPL), or its cofactor, apolipoprotein (apo) C-II. Together, these two proteins initiate the hydrolysis of triglycerides present in chylomicrons and very low density lipoproteins. In the past decade our understanding of the underlying molecular defects that lead to familial chylomicronaemia has been greatly enhanced by the identification of mutations in the genes for LPL and apoC-II. Characterization of these defects has provided new insights into the structure and function of apoC-II and LPL and established the important role that these two proteins play in normal triglyceride metabolism. PMID- 1619389 TI - Metabolic and genetic control of HDL cholesterol levels. AB - Variation of HDL cholesterol levels in man shows a strong inverse relationship to the incidence of atherosclerotic vascular disease. Thus the regulation of HDL cholesterol levels has been the subject of intense investigation. Human genetic differences in cholesteryl ester transfer protein and hepatic lipase illustrate the importance of these factors in the normal catabolism of HDL, while metabolic and population studies show that lipoprotein lipase activity plays a central role in the transfer of lipids and apoproteins into HDL. Metabolic turnover studies in humans suggest that variations in the fractional catabolism of the HDL structural proteins, apoA-I and apoA-II, account for much of the variation of HDL levels in human populations. Although the catabolism of these apolipoproteins is poorly understood, changes in the core lipid composition of HDL may lead to changes in catabolism of the HDL proteins. The core lipid composition of HDL appears to be determined by lipid transfer processes, and the activities of lipoprotein and hepatic lipase. Thus many genetic and environmental factors that influence HDL levels appear to operate by changing the activities of the lipases or the lipid transfer process. PMID- 1619391 TI - How pigeons estimate rates of prey encounter. AB - Pigeons were trained on operant schedules simulating successive encounters with prey items. When items were encountered on variable-interval schedules, birds were more likely to accept a poor item (long delay to food) the longer they had just searched, as if they were averaging prey density over a short memory window (Experiment 1). Responding as if the immediate future would be like the immediate past was reversed when a short search predicted a long search next time (Experiment 2). Experience with different degrees of environmental predictability appeared to change the length of the memory window (Experiment 3). The results may reflect linear waiting (Higa, Wynne, & Staddon, 1991), but they differ in some respects. The findings have implications for possible mechanisms of adjusting behavior to current reinforcement conditions. PMID- 1619392 TI - Instrumental performance following a shift in primary motivation depends on incentive learning. AB - In 5 experiments the role of incentive learning in instrumental performance following a shift in primary motivation was examined. In Experiments 1 and 2 rats trained to perform an instrumental action reinforced by either pellets or maltodextrin when in a low-deprivation state were shifted to a high-deprivation state and tested in extinction. This shift in deprivation increased performance only if the animals had been exposed to the reinforcer in the high-deprivation state prior to instrumental training. Experiments 3, 4, and 5 examined the reverse shift training in a high-deprivation state and testing in a low deprivation state, and found, similarly, that performance was only sensitive to this shift if animals were previously exposed to the reinforcer while in the low deprivation state. These experiments support the conclusion that instrumental performance following revaluation of the reinforcer depends on a process of incentive learning. PMID- 1619393 TI - Responding to a conditioned stimulus depends on the current associative status of other cues present during training of that specific stimulus. AB - The comparator hypothesis is a response rule stating that responding to a Pavlovian conditioned stimulus (CS) reflects the associative strength of the CS relative to that of other cues (comparator stimuli) that were present during CS training. Thus, modulation of the associative strength of a CS's comparator stimulus should alter responding to that CS. These studies examined the stimulus specificity of this effect using within-subjects designs. Rats were trained on 2 CSs, each with a unique comparator stimulus, to determine the degree to which posttraining extinction of the comparator stimulus for one CS influences responding to the other CS. Using negative contingency (Experiments 1 and 2), overshadowing (Experiment 3), and local context (Experiment 4) preparations, stimulus specificity was observed. In each case, posttraining extinction of the comparator stimulus for one CS had greater impact on responding to that CS than on responding to the alternate CS. PMID- 1619394 TI - A configural analysis for feature-negative discrimination learning. AB - In 4 experiments, rats were initially trained with an A+ AXo discrimination in which Stimulus A by itself signaled the delivery of food, A+, whereas the simultaneous presentation of A and X was followed by nothing, AXo. In each experiment X was then paired with food prior to a test phase in which A and X were again presented for a discrimination. The discrimination was of the form A+ AXo in Experiments 1 and 2, whereas it was of the form X+ AXo for Experiments 3 and 4. In all 4 experiments the test discrimination was acquired more rapidly than a control discrimination. The results are interpreted in terms of the original A+ AXo discrimination resulting in the growth of an association between a representation of the entire AX compound and the effects of nonreinforcement. PMID- 1619395 TI - Detection of cryptic prey: search image or search rate? AB - Animals' improvement in capturing cryptic prey with experience has long been attributed to a perceptual mechanism, the specific search image. Detection could also be improved by adjusting rate of search. In a series of studies using both naturalistic and operant search tasks, pigeons searched for wheat, dyed to produce 1 conspicuous and 2 equally cryptic prey types. Contrary to the predictions of the search-rate hypothesis, pigeons given a choice between the 2 cryptic types took the type experienced most recently. However, experience with 1 cryptic type improved accuracy on the other cryptic type, a result inconsistent with a search image specific to 1 prey type. Search image may better be thought of as priming of attention to those features of the prey type that best distinguish the prey from the background. PMID- 1619396 TI - Dissociation of theories of choice by temporal spacing of choice opportunities. AB - Rats were trained on a discrete-trial version of a concurrent variable-interval (VI) variable-ratio (VR) schedule in which the relative reinforcement rates were varied across conditions. Subjects with the shorter intertrial interval (ITI) had a significant bias toward the VR alternative, as predicted by optimality theory, and were also more likely to choose the VI alternative with longer times since responses to the VI alternative, as predicted by momentary-maximizing theory. Subjects with the longer ITI failed to show either of these effects. Approximation to the matching law was greater with the longer ITI. Thus, matching is not derivative of the processes postulated by optimality or momentary maximizing theory but instead is in competition with those processes. PMID- 1619397 TI - Inactivated Lassa virus elicits a non protective immune response in rhesus monkeys. AB - We attempted to protect three rhesus monkeys from Lassa fever by vaccination with a preparation of purified whole Lassa virus which had been inactivated by gamma irradiation. The vaccinated monkeys developed antibodies against the three major viral proteins of Lassa virus demonstrated by radioimmunoprecipitation. When the three vaccinated monkeys and two unvaccinated control monkeys were challenged all five became severely ill and died. Prior to death a secondary, high-titer antibody response to Lassa virus was observed in the three vaccinated monkeys, whereas the two unvaccinated monkeys developed a primary, low-titer antibody response. Though titers of Lassa virus in serum reached peak levels earlier following challenge in the non vaccinated, at the time of death serum and organ virus titers did not differ significantly. Changes in platelet aggregation, leukocyte counts, and liver enzymes, abnormalities of which have been associated with severity of Lassa fever, were found to be comparable in the two groups. The humoral antibody response measured in these animals following vaccination, although of the same magnitude as found in humans recovered from Lassa fever, was insufficient to protect the animals from this fatal disease. Evidence is now accumulating that the cell-mediated immune response must be activated in order to protect against challenge with arenaviruses. PMID- 1619398 TI - Hepatitis E virus: the cause of a waterbourne hepatitis outbreak. AB - Newly developed assays for antibody to hepatitis E virus (HEV) were used to study 114 serum samples collected during an outbreak of enterically transmitted hepatitis that occurred in Kashmir in 1978/9. The sera included samples from patients with viral hepatitis, anicteric hepatitis, contacts of cases, and unaffected persons. A total of 71% of patients with viral hepatitis were found positive for anti-HEV specific IgG, and 75% of these were also positive for IgM. These data confirm the hepatitis E virus as the causative agent in this outbreak. PMID- 1619399 TI - Fine specificity of the humoral immune response to HIV-1 GP160 in HIV-1 infected individuals from Tanzania. AB - A total of 160 sera from HIV-1 infected individuals from Tanzania were examined for their fine specificity characteristics relative to 9 synthetic peptides that define HIV-1 gp160 epitopes. Immunorecessive and immunodominant epitopes were identified in both gp120 and gp41 based on serologic reactivity of these HIV-1 infected sera. A significant difference in fine specificity among HIV-1 infected individuals from Tanzania and the United States was observed for an immunodominant gp41 epitope. No significant differences in reactivity among asymptomatic vs. symptomatic HIV-1 infected individuals were detected for the selected HIV-1 gp160 epitopes defined by these peptides. The majority of sera from HIV-1 infected Tanzanians contained antibodies that recognized a peptide corresponding to the V3 region of gp120 from the HIV-1 MN isolate. These data suggest that regional isolates of HIV-1 may exist in Tanzania that differ from HIV-1 isolated in the United States. However, based on serology, HIV-1 isolates exhibiting sequences with HIV-1 MN V3 similarity may also be prevalent in Tanzania. The results of this study may be useful for the design of more effective AIDS diagnostic and therapeutic products for use worldwide. PMID- 1619400 TI - 1H NMR and UV-Vis spectroscopic characterization of sulfonamide complexes of nickel(II)-carbonic anhydrase. Resonance assignments based on NOE effects. AB - The binding of acetazolamide, p-fluorobenzensulfonamide, p-toluenesulfonamide, and sulfanilamide to nickel(II)-substituted carbonic anhydrase II has been studied by 1H NMR and electronic absorption spectroscopies. These inhibitors bind to the metal ion forming 1:1 complexes and their affinity constants were determined. The 1H NMR spectra of the formed complexes show a number of isotropically shifted signals corresponding to the histidine ligands. The complexes with benzene-sulfonamides gave rise to very similar 1H NMR spectra. The NMR data suggest that these aromatic sulfonamides bind to the metal ion altering its coordination sphere. In addition, from the temperature dependence of 1H NMR spectra of the p-fluorobenzenesulfonamide adduct, a conformational change is suggested. The T1 values of the meta-like protons of the coordinated histidines have been measured and resonance assignments based on NOE experiments were performed. PMID- 1619402 TI - The 13C NMR study of the binding of gold(I) thiomalate with ergothionine in aqueous solution. AB - The interaction of gold(I) thiomalate (Autm) (Myocrysine) with ergothionine (ErSH) has been studied in aqueous solution at pH 7.4. It was found that ErSH forms a ternary complex of the type ErS-Au-tm at a 1:1 mole ratio; unlike other thiols (e.g., cysteine and glutathione) it does not eject thiomalate (Htm) as a free ligand. However, in the presence of glutathione (GtSH), both ligands, ErSH as well as Htm, from the ErS-Au-tm complex were freed. The 13C NMR chemical shifts of C-2 resonance of ergothionine in the presence of Autm shifts greater than imidazolidine-2-thione (Imt) and 1,3-Diazinane-2-thione (Diaz), indicating the stronger complexation of ErS-Au-tm compared to Imt-Au-tm and Diaz-Au-tm. PMID- 1619401 TI - Cytoprotective effect of copper(II) complexes against ethanol-induced damage to rat gastric mucosa. AB - The cytoprotective effect of various copper(II) complexes on the gastric mucosa damage induced by acute intragastric administration of ethanol was investigated. For in vitro experiments, the following copper(II) complexes were tested: Cu(II)(L-Trp)(L-Phe), Cu(II)(L-Leu)Cu(II)(L-Leu-Leu)(L-Leu), Cu(II)(L-Phe-L-Leu), Cu(II)(Gly-His-Lys), and Cu(II)(cyHis)2(ClO4)2. Inorganic copper such as CuSO4 was also tested. The free radical generating system, acting for 2 hr on cardial and fundic mucosa scrapings or mucosal microsomes, was Fe++ (20 microM)/ascorbate (0.25 mM). We found a marked inhibition to 75% of lipid peroxidation in the range 10-100 mM, regardless of whether copper was given in complexed or inorganic form. The results suggest that nontoxic copper(II)-amino acid complexes are able to neutralize oxygen-derived free radicals. In addition, copper(II) complexes suppressed membrane lipid peroxidation when mucosa homogenates were exposed to t butyl hydroperoxide (1-20 microM) plus Fe++ (50 microM). In vivo experiments on rat stomachs, pretreated p.o. by gavage either with Cu(II)(L-Trp)(L-Phe) as paradigmatic agent or with copper sulphate at equivalent doses in the range 3-30 mg/kg body weight showed a significant decrease (30 min after 95% ethanol administration) in the number and severity of mucosal hemorrhagic lesions. In the gastric mucosa scrapings of copper-treated rats after ethanol exposure, we found that malondialdehyde and conjugated diene levels were unchanged compared to those of untreated controls; five enzyme activities released from lysosomes were near control values. In isolated mucosal cells, whether or not pretreated with 200 microM solution of either Cu(II)(L-Trp)(L-Phe) or CuSO4, the release of cathepsin D activity was also unmodified. The results suggest that the cytoprotective effect of Cu(II) complexes against ethanol-induced mucosal lesions was not associated in vivo to lipid peroxidation. PMID- 1619403 TI - Synthesis, characterization, and microbiocidal activity of alpha-methyl-(2 thiophenomethylene) aryloxyacetic acid hydrazides and their metal complexes. AB - Complexes of alpha-methyl-(2-thiophenomethylene) aryloxyacetic acid hydrazides with Cu(II) and Zn(II) metal salts were synthesized and characterized by elemental analysis, molecular weight determination, molar conductance, and magnetic moment and spectroscopic techniques. In these complexes, the ligands form a conjugate O-N-S tridenate system, thus coordinating with metal through oxygen of the carbonyl group, nitrogen of azomethine, and sulphur of thiophenemoiety. Octahedral geometry is proposed for all the complexes. Antifungal activity of the ligands and their Cu(II) and Zn(II) complexes was determined against plant pathogenic fungi viz. Alternaria alternata, Rhizoctonia solani, Colletotrichum capsicum, and Glomeralla cingulata at 28 degrees C. Antibacterial activity of ligands and their metal complexes was determined on gram positive Bacillus subtilis and gram negative Escherichia coli bacteria at 37 degrees C by the serial dilution method. In some cases an increase in biocidal activity of the ligands on coordination with metal ions was observed in terms of minimum inhibitory concentration (MIC) values. PMID- 1619404 TI - The relevance to psychiatry of recent advances in functional imaging. PMID- 1619405 TI - Jean Nicot 1530-1600. PMID- 1619406 TI - Measuring visual neglect in acute stroke and predicting its recovery: the visual neglect recovery index. AB - An overall measure of the recovery of visual neglect in patients with an acute stroke is described: The "Visual Neglect Recovery Inde" (VNRI) expresses the amount of visual neglect on a battery of visual neglect tests as a percentage of complete recovery from the maximal visual neglect measurable. The principles underlying the development of the index are similar to those involved in the development of the Motricity Index for hemiplegia. A population of 68 survivors of stroke who presented with visual neglect at two to three days were followed for up to six months. The VNRI showed that neglect was greater in those with right hemisphere stroke than in those with left hemisphere stroke and that recovery was most rapid over the first 10 days and reached a plateau at three months. Most patients, including many with severe initial visual neglect, showed little visual neglect at three months. Stepwise regression analysis showed that the severity of visual neglect at three months and at six months post-stroke could be predicted by the severity of visual neglect and the presence of anosognosia at two to three days. A regression equation was produced which may enable clinicians to select patients for intensive treatment of visual neglect. PMID- 1619407 TI - Migraine aura without headache: transient ischaemic attack or not? AB - Patients with "migraine aura without headache" can be separated from those with transient ischaemic attacks (TIA) on the basis of the onset of symptoms, which is generally gradual and which spread or intensify over minutes or hours, and from the typical migrainous nature of their visual symptoms. Fifty cases were prospectively identified and these were compared with 50 age matched patients with a TIA. Surprisingly, there were no significant differences in the prevalence of vascular risk factors and diseases in the two groups although those with TIAs tended to have more. Only one patient with "migraine aura without headache" suffered a subsequent vascular event (a myocardial infarction). Three patients with TIAs had strokes and two others died from vascular disease. Although the results are not conclusive, they do suggest that patients with the clinical characteristics of "migraine aura without headache" have a low risk of subsequent vascular events, lower than those with TIAs, despite perhaps having similar prevalence of vascular risk factors. Although their risk factors should be treated, patients with "migraine aura without headache" should be reassured and not subjected to inappropriate and potentially hazardous investigations and treatment. PMID- 1619409 TI - The site of brainstem lesions causing semicircular canal paresis: an MRI study. AB - Ten patients with canal paresis of central origin and ten patients with peripheral canal paresis were studied using MRI of the brainstem to identify lesions within the central vestibular pathways. In the central group, the magnitude of the canal paresis was generally lower than in the peripheral group and removal of fixation had little effect on the nystagmic response. In the peripheral group, removal of fixation enhanced the nystagmus and lessened the discrepancy between the two ears. Statistical processing of the MRI showed that in the central group significant spatially coincident lesions occurred within the medial vestibular nucleus, lateral vestibular nucleus and proximal portion of the vestibular fascicle. PMID- 1619408 TI - Lacunar versus non-lacunar infarcts: pathogenetic and prognostic differences. AB - To characterise the pathogenetic and prognostic features of lacunar infarcts, 88 patients with these infarcts were compared with 103 patients with non-lacunar infarcts. Potential cardioembolic sources were significantly more frequent among patients with non-lacunar infarcts (p = 0.0025). Although the prevalence of hypertension was higher among lacunar infarcts, this difference was not statistically significant. However, the distribution of hypertensive patients in the two groups of lacunar and non-lacunar infarcts was influenced by the presence or absence of cardioembolic sources: hypertension was significantly associated with the presence of cardioembolic sources among non-lacunar infarcts, whereas among lacunar infarcts it was significantly more frequent in patients without a cardioembolic source. This indicates that cardioembolism may exert a confounding effect by suppressing the relation between hypertension and lacunar infarcts. In a mean follow up period of 28.1 months, lacunar infarcts had a significantly lower incidence of stroke recurrence and of myocardial infarction (age-adjusted survival analysis: p = 0.0008); mortality from all causes was also lower in patients with lacunar infarct (age-adjusted survival analysis: 0.04 less than p less than 0.05). In a multivariate regression analysis, stroke subtype was an independent predictor of new major vascular events. These findings support the lacunar hypothesis and should be considered in the planning of epidemiological and therapeutic studies in patients with cerebral infarction. PMID- 1619410 TI - High dose steroids in acute relapses of multiple sclerosis: MRI evidence for a possible mechanism of therapeutic effect. AB - The integrity of the blood-brain barrier (BBB) in multiple sclerosis (MS) was monitored by serial gadolinium-(Gd)-DTPA enhanced MRI during and after the treatment of acute relapses with a three day course of high dose intravenous methylprednisolone (IVMP). During treatment there was a rapid reduction of BBB abnormalities in 96% of enhancing lesions. In spite of sustained clinical improvement, many lesions re-enhanced within a few days of stopping IVMP, and new lesions frequently appeared within one month. It is possible that the rapid, albeit transient, reversal of BBB abnormalities contributes to the accelerated recovery from relapses associated with IVMP treatment. PMID- 1619411 TI - Effect of practice on performance of a skilled motor task in patients with Parkinson's disease. AB - Parkinson's disease leads to a breakdown in the execution of highly practised, skilled movements such as walking and handwriting. The improved execution of skilled movements with practice can be understood as a process of schema learning, the determining of the relevant parameters of the specific movement. The ability of patients with Parkinson's disease and age matched normal control subjects to improve their performance, with practice, on a skilled motor task, doing up buttons, was assessed. The task was assessed on its own and with simultaneous foot tapping. Both groups showed an initial improvement in the task on its own and deterioration in performance when buttoning with foot tapping. The amount of interference, however, decreased with practice, particularly in the patients with a 2 Hz tapping rate. The results suggest that patients with Parkinson's disease are capable of schema learning but require more practice than control subjects to achieve comparable levels of performance. This may be a reflection of the fundamental motor dysfunction of the disease rather than a specific learning deficit. PMID- 1619412 TI - Value of somatosensory evoked potentials in saphenous entrapment neuropathy. AB - Neuralgia of the saphenous nerve (SN) is a rare clinical syndrome simulating a vascular disorder of the lower extremities. In four cases, the presenting complaint was persistent pain on the medial aspect of the knee. Examination revealed tenderness over the site of exit of the SN form the femoral canal. Femoral nerve motor conduction, quadriceps H-reflex and EMG of the leg muscles were normal. The sensory nerve action potential of the SN in the leg was not obtained in some patients, even in the unaffected leg. SEP were therefore preferred for diagnosis and performed at the infrapatellar and descending branches of the right and left SN and recordings from the Cz'-Fz electrode. Latency and amplitude differences were evaluated and compared with a control group of healthy subjects. An alteration in the SEP from one branch was observed on the painful side. Posterior tibial responses were normal. In one case, pain resolved immediately after neurolysis, confirming SN entrapment above the femoral canal, before its division. Pain resolved in two other cases and persisted in the last after medical treatment. SEP studies are valuable in the diagnosis of an isolated lesion of the SN. PMID- 1619414 TI - Motor and somatosensory evoked potentials in coma: analysis and relation to clinical status and outcome. AB - Central sensory and motor conduction were studied in 23 comatose and three brain dead patients. Motor evoked potentials (MEPs) to transcranial magnetic (magMEP) and electrical (elMEP) stimulation were recorded from the hypothenar muscle, and somatosensory evoked potentials (SEPs) were recorded after median nerve stimulation. Comparison of clinical with evoked potential (EP) findings revealed: 1) a painful stimulus applied to the skin of the arm lowered excitation threshold to cortical stimulation and was a prerequisite to obtain MEPs in 14 instances; 2) only in braindead patients were all EPs abolished simultaneously and bilaterally; 3) MEPs (p less than or equal to 0.05, chi 2-Test), but not necessarily SEPs (p greater than 0.1) were preserved in the arms that showed normal motor reaction during clinical examination; 4) no correlation was found between EP findings and the Glasgow Coma Scale (GCS). The results of clinical and EP testing were examined in the light of the patient's outcome 10 months later: 1) fatal outcome was predicted by a GCS of three (38% of cases, p less than or equal to 0.05, Fisher's exact test), abolished brainstem- or papillary reflexes (38%, p less than or equal to 0.05), the combination of these clinical signs (54%, p less than or equal to 0.01), bilateral abolition of elMEPs (38%, p less than or equal to 0.05), magMEPs (38%, p less than or equal to 0.05), or SEPs (23%, p greater than 0.1), or a combination of clinical and EP data (85%, p less than or equal to 0.0005); 2) good outcome was predicted by a GCS of greater than or equal to 8 only in post-traumatic coma, and EPs did not help to predict fatal outcome of coma; 1) if this appears impossible on the basis of clinical data alone; 2) if a second indicator is needed to confirm a clinical impression; 3) SEPs may be first evaluated during the acute stage of coma treatment, because they can be recorded in the presence of anaesthetic or relaxant agents; 4) MEP may be studied if outcome prediction remains ambiguous, and if the clinical situation allows for discontinuation of these agents. PMID- 1619413 TI - Unilateral brain damage after prolonged hemiconvulsions in the elderly associated with theophylline administration. AB - The brains of 14 elderly patients who died after status epilepticus were examined pathologically. Three of the 14 patients showed unilateral brain damage which corresponded to the side of the seizures, and the lesions were thought to be caused by seizures. In these three and two other patients, no causative lesion related to the seizures was found. In these five patients, status epilepticus occurred during theophylline therapy and thus the seizures in these five patients were assumed to be induced by theophylline. In the three patients with unilateral brain damage, the damage was seen in the hippocampus, amygdala and thalamus in two patients, while in the third, the whole hemisphere was damaged, including the hippocampus, amygdala, thalamus, basal ganglia and cerebral cortex. The distribution of pathological changes within the thalamus was described. It is suggested that the thalamus was primarily affected by seizures, rather than by secondary degeneration from the cortex. PMID- 1619415 TI - Behavioural and psychosocial sequelae of severe closed head injury and regional cerebral blood flow: a SPECT study. AB - Thirty six patients (31 male, 5 female) who had suffered severe closed head injury were re-examined at an average of 39.3 (SD 12.8, range 7-66) months after the injury. Behavioural symptoms were measured using the Giessen test. The relatives' reports were used for data analysis to ensure that results were valid. The neurophysical impairment subscale of the Glasgow assessment schedule was completed by two neurologists, and the number connection test was completed by each patient. The adjective mood scale was completed by each relative. All patients were investigated by single photon emission computerised tomography (SPECT). Exploratory factor analysis using the principal components method was carried out separately for SPECT results and psychological measures and correlations were sought between the resulting factors. Factor analysis of the data from the Giessen test identified social isolation, disinhibition, and aggressive behaviour as major components of post-traumatic personality changes; it indicates that these behavioural features are independent of the level of neurological and neuropsychological impairment, which loaded on a single independent factor. Relatives' psychic health seemed to be relatively resistant to physical and cognitive disability and was mainly affected by disinhibitive behaviour. The highest correlation was between frontal flow indices and disinhibitive behaviour (p less than 0.01): the severity of disinhibition increased with lower frontal flow rates. There was a significant but somewhat weaker correlation (p less than 0.05) between flow indices of the left cerebral hemisphere and social isolation. Low flow values of the right brain regions were related to aggressive behaviour (p less than 0.05). Neurological and cognitive impairment correlated negatively with the thalamus; worse neurological and cognitive performance indicate by raised scores on the neurophysical scale and on the number connection test was associated with low thalamic flow values. The results support the importance of lesion location in the production of post traumatic behavioural disorders. PMID- 1619416 TI - Surgical outcome in an elderly population with intracranial meningioma. AB - Thirty seven patients aged 70 and over (mean = 74 years) with an intracranial meningioma who had craniotomy between the years 1978-88 were reviewed. There were 20 women and 17 men. Resection was total in 28 (76%) and subtotal in 9 (24%) cases and each tumour was histologically verified. The location of the tumours were: base of skull 11, convexity 10, parasagittal 9, falx 6, and tentorial 1. The most frequent associated diseases were: hypertension (35%), chronic ischaemic heart disease (22%) chronic obstructive pulmonary disease (19%), and diabetes (14%). The Karnofsky Scale (KS) score before surgery ranged from 30 to 90 (mean = 59). It was less than 40 in ten patients. The length of anaesthesia during the surgical procedure varied from 4 to 12 hours and was not related to the outcome. There were two perioperative deaths (mortality = 5.4%). There were major complications in 8 patients and minor complications in 7 patients. In a mean follow up period of 29 months (shortest 6 and longest 96 months) the results were: excellent (KS 90-100) 39%, good (KS 70-80) 49%, fair (KS 60) 6%, and poor (KS 40-50) 6%. The difference between the mean preoperative KS value (KS = 59) and the mean postoperative KS value (KS = 80) was statistically significant (P less than 0.001). The results support a more aggressive therapeutic approach to the elderly patient with an intracranial meningioma. PMID- 1619417 TI - Mifepristone (RU 486) treatment of meningiomas. AB - Meningiomas are common brain tumours which are generally benign, well circumscribed and slow growing. In a minority of patients complete surgical removal is not possible and re-growth of tumour tissue is a major clinical problem. Most meningiomas contain progesterone receptors. The anti-progestational drug mifepristone (RU 486) binds to these receptors. Ten patients were treated with 12 recurrent or primary "inoperable" meningiomas, all of whom had shown recent neuroradiological and/or ophthalmological evidence of tumour growth. They received 200 mg mifepristone daily for 12 months. Most patients initially had complaints of nausea, vomiting and/or tiredness. In four patients prednisone (7.5 mg/day) was given after which these side-effects subsided. CT scan analysis of tumour size, showed progression of growth of five meningiomas in four patients, stable disease in three patients with three tumours and regression of four tumours in three patients. A decrease in the complaints of headache and an improved general well being was observed in five patients. Two patients died during the treatment period from unrelated causes. Mifepristone treatment resulted in control of tumour growth (= stable disease) in six of 10 patients who had shown recent evidence of tumour growth. In three of these six patients consistent tumour shrinkage was observed. PMID- 1619419 TI - Delayed diagnosis of juvenile myoclonic epilepsy. AB - Fifteen cases of juvenile myoclonic epilepsy (JME) were identified from one hundred and eighty consecutive patients referred to a new epilepsy clinic at St Thomas' Hospital between April 1989 and December 1990, a prevalence of 8.3%. Of these, only one was referred with a putative diagnosis of JME. Diagnosis of the other patients on referral included "epilepsy", "grand mal", "temporal lobe epilepsy", "photoconvulsive epilepsy" and "alcohol-induced epilepsy". At least 11 of the 15 patients had been seen by a neurologist in the United Kingdom before referral. Definitive diagnosis was delayed by a mean of 14.5 years. In seven patients inappropriate anticonvulsants had been prescribed. Control of seizures was improved in most patients after diagnosis. Factors responsible for the delay in diagnosis include lack of familiarity with the syndrome, failure to elicit a history of myoclonic jerking and high prevalence of focal abnormalities on the EEG. Precipitation of fits by alcohol and sleep deprivation may not be recognised by the physician as part of the syndrome of JME. Diagnosis may also be delayed in patients whose absence and generalised tonic-clonic seizures pre-date myoclonic jerks. PMID- 1619418 TI - Preoperative psychological adjustment and surgical outcome are determinants of psychosocial status after anterior temporal lobectomy. AB - This investigation evaluated the role of preoperative psychological adjustment, degree of postoperative seizure reduction, and other relevant variables (age, education, IQ, age at onset of epilepsy, laterality of resection) in determining emotional/psychosocial outcome following anterior temporal lobectomy. Ninety seven patients with complex partial seizures of temporal lobe origin were administered the Minnesota Multiphasic Personality Inventory (MMPI), Washington Psychosocial Seizure Inventory (WPSI), and the General Health Questionnaire (GHQ) both before and six to eight months after anterior temporal lobectomy. The data were subjected to a nonparametric rank sum technique (O'Brien's procedure) which combined the test scores to form a single outcome index (TOTAL PSYCHOSOCIAL OUTCOME) that was analysed by multiple regression procedures. Results indicated that the most powerful predictors of patients' overall postoperative psychosocial outcome were: 1) The adequacy of their preoperative psychosocial adjustment, and 2) A totally seizure-free outcome. Additional analyses were carried out separately on the MMPI, WPSI, and GHQ to determine whether findings varied as a function of the specific outcome measure. These results were related to the larger literature concerned with the psychological outcome of anterior temporal lobectomy. PMID- 1619420 TI - Pure alexia and right hemiachromatopsia in posterior dementia. AB - A 66 year old, right handed woman presented with pure alexia and right hemiachromatopsia (PARH) in the context of a posterior dementia. PARH was accompanied by prosopagnosia, 2-D object agnosia, and environmental agnosia. Visual fields were normal to confrontation testing. The pathological anatomy of PARH involves circumscribed damage to the lingual and fusiform gyri and paraventricular white matter of the left occipital cortex, two contiguous cortical regions functionally specialised for processing colour and word form information, respectively. PMID- 1619421 TI - Impairment in bilateral alternating movements in Parkinson's disease? AB - Although problems in bilateral simultaneous movements in Parkinson's disease (PD) are well known, such deficits have not been reported to be any more impaired than simultaneous movements within the same limb. This is surprising, since (a) the parallels between supplementary motor area (SMA) damage and PD are well documented and (b) the SMA seems to play a special role in bilateral motor control. Bilateral versus unilateral movements in PD were examined by using a task that compared alternating movements of fingers of the same hand with alternating movements of fingers of the opposite hands. PD patients showed particular problems in programming and transferring motor activity to fingers on the opposite side of the body, as opposed to switching motor activity between fingers on the same side of the body. These findings outline the relevance of SMA dysfunction to PD. PMID- 1619422 TI - The neuropsychology of hanging: an historical perspective. PMID- 1619423 TI - A neurological audit in Vitoria, Spain. PMID- 1619424 TI - HLA antigens in familial Guillain-Barre syndrome. PMID- 1619425 TI - Adult onset acid maltase deficiency associated with epilepsy and dementia: a case report. PMID- 1619426 TI - A reappraisal of "direction of scratch" test: using somatosensory evoked potentials and vibration perception. PMID- 1619427 TI - Seventh nerve palsy as a false localising sign. PMID- 1619428 TI - Lumbosacral meningoradiculitis associated with Chlamydia pneumoniae infection. PMID- 1619429 TI - Postoperative fourth ventricle tension pneumocephalus. PMID- 1619430 TI - Hospital outpatient clinics, a neurology audit in south Catalonia. PMID- 1619431 TI - The brain in schizophrenia. PMID- 1619432 TI - The neuropsychological sequelae of attempted hanging. PMID- 1619433 TI - A predominantly cervical form of spinal muscular atrophy. PMID- 1619434 TI - Defining prognosis in medical coma. PMID- 1619435 TI - A prospective study of physical trauma and multiple sclerosis. PMID- 1619436 TI - Multiple sclerosis, tropical spastic paraparesis and HTLV-I infection. PMID- 1619437 TI - Neuropathological features of Alzheimer's disease in non-demented parkinsonian patients. PMID- 1619438 TI - The evolution of brain infarcts. A review. PMID- 1619439 TI - Arcuate nucleus hypoplasia in the sudden infant death syndrome. AB - Abnormalities in central respiratory control during sleep, arousal and/or cardiac activity have been reported in some infants who subsequently die of the sudden infant death syndrome (SIDS). We postulate that these abnormalities may result from dysfunction of the ventral and ventrolateral medulla, which, based on animal data, is an integrative site for chemosensitivity, ventilation, autonomic function, and arousal. The arcuate nucleus along the ventral surface of the human medulla has been proposed to facilitate chemosensitivity to carbon dioxide and/or hydrogen ion. In this study, we surveyed serially or extensively sectioned medullae of 41 SIDS and 27 controls, and identified two SIDS victims with isolated hypoplasia of the arcuate nucleus. Three-dimensional reconstructions and volume measurements of each hemimedulla of one of these SIDS victims and three controls were performed from serial sections. The volume of the right arcuate nucleus of the SIDS case was 0.7 mm3, compared to a range of 3.4-26.3 mm3 (median 5 mm3) in three infant controls. On the basis of the anatomic connections of the human arcuate nucleus and of neurons in homologous positions in animals, we postulate that arcuate hypoplasia may lead to death by dyssynergy between cerebellar coordination of ventilation and autonomic/chemosensory/arousal integration, especially during sleep, hypercarbia, and in a critical developmental period. PMID- 1619440 TI - Three-dimensional analysis of the relationship between synaptic pathology and neuropil threads in Alzheimer disease. AB - Recent studies have shown that the Alzheimer disease (AD) neocortex is characterized by a loss of large neurons, the presence of dilated terminal axons, widespread loss of synapses, and a disruption of the dendritic cytoskeleton which is manifested as Tau immunoreactive threads. In the present study we have investigated the relationship between synaptic and dendritic abnormalities in the neocortex of Alzheimer patients and examined the extent to which these structural alterations correlate with the severity of cognitive impairment in AD. Quantitative neuroanatomical data were obtained from immunofluorescence-labeled specimens using a laser-scanning confocal microscope, computer-assisted image processing and serial section reconstruction techniques. We found that the AD cases showed a 34% loss in the number of presynaptic terminals per 100 square (sq) microns, many of which showed structural abnormalities. The AD neuropil had an average of 10 +/- 7 dendritic threads per 1,000 sq microns, with the average thread measuring 2 sq microns. Severe AD cases had thicker threads compared with mild to moderate AD cases. Three-dimensional analysis showed clustering of synapses around threads, as well as presynaptic boutons apposed to dendritic neuropil threads. Statistical analysis showed that the strongest correlation was between synapse density and Blessed score of cognitive impairment. Thread counts did not correlate with either but were correlated with tangle counts. Stepwise multiple regression analysis showed that tangle counts, but not threads, strengthened the correlation between Blessed score and synapses. We conclude that synaptic damage may precede dendritic thread and tangle formation, and that threads do not necessarily induce synaptic pathology. Instead, dendrite sprouting in the denervated regions could be associated with increased accumulation of cytoskeletal proteins observed in the dendritic threads. PMID- 1619441 TI - Effects of spaceflight in the adductor longus muscle of rats flown in the Soviet Biosatellite COSMOS 2044. A study employing neural cell adhesion molecule (N-CAM) immunocytochemistry and conventional morphological techniques (light and electron microscopy). AB - The effects of spaceflight upon the "slow" muscle adductor longus were examined in rats flown in the Soviet Biosatellite COSMOS 2044. The techniques employed included standard methods for light microscopy, neural cell adhesion molecule (N CAM) immunocytochemistry and electron microscopy. Light microscopic observations revealed myofiber atrophy and segmental necrosis accompanied by cellular infiltrates composed of macrophages, leukocytes and mononuclear cells. Neural cell adhesion molecule immunoreactivity (N-CAM-IR) was seen on the myofiber surface and in regenerating myofibers. Ultrastructural alterations included Z band streaming, disorganization of myofibrillar architecture, sarcoplasmic degradation, extensive segmental necrosis with apparent preservation of the basement membrane, degenerative phenomena of the capillary endothelium and cellular invasion of necrotic areas. Regenerating myofibers were identified by the presence of increased amounts of ribosomal aggregates and chains of polyribosomes associated with myofilaments. The principal electron microscopic changes of the neuromuscular junctions showed axon terminals with a decrease or absence of synaptic vesicles replaced by microtubules and neurofilaments, degeneration of axon terminals, vacant axonal spaces and changes suggestive of axonal sprouting. The present observations suggest that alterations such as myofibrillar disruption and necrosis, muscle regeneration and denervation and synaptic remodeling at the level of the neuromuscular junction may take place during spaceflight. PMID- 1619443 TI - Inbred SAM-P/10 as a mouse model of spontaneous, inherited brain atrophy. AB - We developed a novel inbred strain of mouse with age-related brain atrophy and it was named "Senescence Accelerated Mouse (SAM)-P/10." Macroscopic morphometry indicated that the brains of SAM-P/10 showed age-dependent involutional changes mainly in the frontal portion of the cerebrum. The brain weight decreased by 8.6% throughout the life-span. There were no obvious defects in postnatal development. Semi-macroscopic morphometry revealed a prominent atrophy in the neocortex, olfactory cortex and amygdala. Microscopic morphometry showed that the neocortical neurons were lost with aging, with mostly the large neurons being affected which were lost by 35.6% throughout the life-span. Somata of the neocortical neurons shrank with advancing age. In a control SAM-R/1 strain with only a slight macroscopic involutional change in the brain without weight loss, neither loss of the neocortical large neurons nor shrinkage of the neocortical neurons was evident with aging. Learning and memory skills were evaluated using the one-trial passive avoidance task and conditional avoidance task. Young SAM P/10 mice performed well in both tasks but older SAM-P/10 showed a poorer performance in both tasks, and this was even poorer than the performance of very old SAM-R/1 mice. Thus, SAM-P/10 can serve as a spontaneous animal model of brain atrophy for a variety of studies of aging of the brain. A better understanding of neurodegenerative diseases with dementia should be forthcoming. PMID- 1619442 TI - Herpes simplex virus type I (HSV I)-induced multifocal central nervous system (CNS) demyelination in mice. AB - Multifocal central nervous system (CNS) demyelination develops in the brains of SJL/J, PL/J, and A/J mice following lip inoculation with a specific strain of herpes simplex virus I (HSV I). The lesions in all three inbred strains of mice share similar characteristics including demyelination, relative preservation of axons, and a mononuclear cell (MNC) infiltrate. The lesions, developing during the early phase of demyelination, also appear sequentially in the CNS (trigeminal root entry zone of the brainstem greater than cerebellum greater than cerebral hemispheres) of all three strains of mice but differ in the time of their initial appearance following infection as well as their morphology. In SJL/J mice, new areas of demyelination are observed for only 24 days following lip inoculation with virus. Late stage multifocal CNS demyelination persists throughout 28 weeks postinoculation (pi) in PL/J mice while in A/J mice the development of new areas of demyelination are restricted to 8 weeks pi. Although mononuclear inflammatory cells are present in the new areas of demyelination in either PL/J or A/J mice, viral antigens are not detected in the CNS beyond 12 days pi. In contrast, in situ hybridization studies using 35S-cDNA HSV probes and performed beyond day 12 pi identify probe-positive cells central to a number of the multifocal CNS demyelinating lesions in A/J mice. Results from studies with inbred and congenic strains of mice indicate that the major histocompatibility complex (H-2) does not determine the development of multifocal CNS demyelination following lip inoculation with HSV I but does influence the morphological appearance of the lesions that do develop. PMID- 1619444 TI - The role of pyrrole formation in the alteration of neurofilament transport induced during exposure to 2,5-hexanedione. AB - Exposure to the gamma-diketone, 2,5-hexanedione (HD), results in the accumulation of neurofilaments within the distal axon and is associated with acceleration of neurofilament transport within the proximal axon. The epsilon-amino groups of lysyl residues react with HD forming pyrrole adducts, followed by pyrrole mediated protein crosslinking. Both reaction steps have been proposed as mechanisms causing neurofilament accumulation and acceleration of transport. In order to assess the importance of these steps on neurofilament transport, we compared transport in the optic system of rats exposed to HD and 3-acetyl-2,5 hexanedione (AcHD), a non-toxic analog of HD which forms pyrroles but does not crosslink proteins. Control, HD-treated, and AcHD-treated rats received intraoptic injections of [35S]-methionine and were exposed to saline, HD, or AcHD by intraperitoneal injections before and during the period of neurofilament transport. Neurofilament triplet proteins in the optic nerve and tract were identified by polyacrylamide gel electrophoresis followed by fluorography. The rate of neurofilament transport was accelerated in HD-treated animals over that of controls. However, despite higher levels of protein-bound pyrroles in AcHD treated animals, the rate of transport was indistinguishable from that of controls. These findings indicate that pyrrole formation alone is not sufficient to cause acceleration of neurofilament transport. PMID- 1619446 TI - Insulin-like growth factor II expression in the developing human brain. AB - Insulin-like growth factor II (IGF-II) is a polypeptide hormone with insulin-like metabolic activity and neurotrophic activity in vitro that has been implicated in human brain development. In this study, we used northern blot analysis to examine the patterns of IGF-II mRNA expression in selected regions of 18 human brains from cases ranging in age from 20 gestational weeks to 2.5 years (median age 31 gestational weeks). The expression of IGF-II mRNA was widespread throughout the brain from midgestation through the perinatal period. Each region showed a distinct developmental pattern of expression and IGF-II mRNA levels varied considerably between regions. The highest levels of expression at all ages were in leptomeninges and choroid plexus. After two postnatal months, IGF-II mRNA virtually disappeared from parenchymal regions. Beyond the perinatal period, IGF II expression persisted primarily in choroid plexus. Transcripts of both 6.0 and 4.8 kb were detected in most brain regions. A developmental change in the relative amounts of the two transcripts occurred in choroid plexus, leptomeninges and medulla. The expression of IGF-II mRNA in the brain parenchyma during the last half of gestation correlates with a period of major brain growth and supports the hypothesis that high levels of IGF-II stimulate the proliferation and differentiation of neural cells early in development. PMID- 1619445 TI - Clinically-silent mutation in the putative iron-responsive element in exon 17 of the beta-amyloid precursor protein gene. AB - Three missense mutations in exon 17 of the beta-amyloid precursor protein (APP) gene have been reported to cosegregate in families with early onset Alzheimer's disease (AD). All three mutations result in amino acid substitutions at codon 717 and may produce AD by altering the structure of the transmembrane domain of APP. Alternatively, the mutations may destabilize the stem of a putative iron responsive element (IRE) in which they lie and confer pathogenicity by inactivating this negative regulatory element. We have detected a clinically silent mutation in codon 716 that would also be expected to disrupt the putative IRE but results in no amino acid substitution. This result strongly suggests that the missense mutations at codon 717 produce AD by altering the amino acid sequence of APP rather than the IRE. Furthermore, the identification of a clinically-silent mutation among four point mutations that span only three nucleotides of exon 17 suggests that this region may be a mutational "hot" spot. PMID- 1619447 TI - Third meeting of the European Neurological Society. 27 June-1 July 1992, Lausanne, Switzerland. Abstracts. PMID- 1619448 TI - The effects of gender and age on associations between blood lipid levels and obesity in Danish men and women aged 35-65 years. AB - The purpose of the study was to assess the influence of gender and age on the associations between different measures of obesity, and blood lipid levels. Overall obesity (body fat, body fat percentage and body mass index) or abdominal obesity (waist/hip-ratio, waist/thigh-ratio and waist-circumference) and lipid levels [high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), total cholesterol and triglyceride level] were measured in 1987/88 in a random Danish population sample of men and women (N = 2987), aged 35, 45, 55 and 65 yr. All lipid levels were dependent on gender and age. The associations between most measures of obesity and HDL or LDL were independent of gender and age, whereas, with a few exceptions, associations between measures of obesity and total cholesterol, VLDL or triglycerides were dependent on gender and/or age. Compared to levels of HDL, LDL and total cholesterol, abdominal obesity specifically affected levels of VLDL or triglycerides, whereas overall obesity affected HDL, LDL, VLDL, total cholesterol and triglyceride levels more evenly. When men and women were compared, associations between the measures of obesity and blood lipids were stronger in men than in women of the same age, except for the associations between measures of abdominal obesity and VLDL or triglycerides in 45-year-old women. No age trend was found for associations between the measures of obesity and VLDL or triglycerides, whereas young age-groups showed stronger associations between obesity and total cholesterol than older age-groups. Failure to consider age/gender effects induces bias and may lead to misleading conclusions regarding the bivariate association between obesity and lipids, and further may make results from population studies incomparable. PMID- 1619450 TI - Comparison of "Rose Questionnaire Angina" to exercise thallium scintigraphy: different findings in males and females. AB - Validation of the London School of Hygiene (Rose) Questionnaire with objective measures of myocardial ischemia is incomplete. Therefore, we compared the Rose Questionnaire with exercise thallium-201 myocardial scintigraphy in 147 male and 97 female patients with chest pain referred for clinical exercise testing. Of those with "Rose Questionnaire angina", 26% of the females and 73% of the males had positive thallium-201 scans. Negative results on both the Rose Questionnaire and thallium-201 scintigraphy were observed in 71% of the females and 47% of the males. The sensitivity of the Rose Questionnaire was similar in females (41%) and males (44%). The specificity was 77% in males, while in females it was significantly lower at 56%. The specificity values reflect the higher (p less than 0.05) prevalence of "false positive" Rose Questionnaire results in females (75%) compared with males (27%). In addition, males had a greater (p less than 0.05) number of "false negative" results (53%) than females (29%). The accuracy of the Rose Questionnaire for myocardial ischemia was 0.19 in females, 0.48 in males, and 0.29 overall when including both males and females. Our results indicate a generally poor relationship between Rose Questionnaire angina and thallium-201 scintigraphy, an objective measure of myocardial ischemia in patients with chest pain referred to clinical exercise testing. Further, there are gender-specific differences in this relationship between the questionnaire and exercise thallium-201 imaging. PMID- 1619449 TI - Identification of fractures from computerized Medicare files. AB - Study of non-hip fractures, which are a serious public health problem for persons greater than or equal to 65 years of age, has been hindered by the absence of an economical method for case identification. We assessed the utility of computerized Medicare inpatient, emergency room, hospital outpatient department and physician claims for identifying fractures in an elderly Tennessee Medicaid population. We used these files for 1987 to identify 3086 possible fractures and reviewed medical records for a sample of 1440. Using this sample, we developed a definition of probable fractures that excluded claims unlikely to represent newly diagnosed fractures. For all fractures, this definition had a positive predictive value of 94%, which for individual fracture sites, ranged from 79% (tibia/fibula) to 98% (hip). Of fractures in the reviewed sample, 91% were identified as probable fractures; this upper bound for sensitivity varied between 75% (femoral shaft) and 100% (patella). These data suggest that computerized Medicare files can be used for rapid and economical fracture ascertainment among persons greater than or equal to 65 years of age. However, further work is needed to obtain better estimates of sensitivity. PMID- 1619451 TI - Data collection strategies in genetic epidemiology: The Epilepsy Family Study of Columbia University. AB - A large-scale study of genetic influences on seizure disorders is described here as a primer of tested methods for collection of family history data. 1957 adult probands with epilepsy were ascertained from voluntary organizations. Personal and family history data were obtained from probands in semistructured telephone interviews. To increase sensitivity, an independent family history was obtained from a second family informant in a similar interview. To increase specificity and diagnostic detail, family members reported to be affected were interviewed, and medical records of probands and affected relatives were collected. Participation rates for probands were 84-90%. Interviews were completed with second informants in 67% of families, and with 51% of eligible affected relatives. The main reasons for non-interview were lack of permission from probands and difficulties in locating relatives. Although 90% of probands gave verbal permission for medical record review, only 75% of these signed and returned consent forms for this purpose. Physicians returned 87% of the records requested. The resulting proportion of probands with medical records was 59%. These findings illustrate the complexity involved in assembling useful databases in genetic epidemiology. PMID- 1619452 TI - Further thoughts on the importance of models in the assessment of clinical evidence. PMID- 1619453 TI - Coffee consumption and cause-specific mortality. Association with age at death and compression of mortality. AB - The relationship between reported coffee consumption and specific causes of death was examined in 9484 males enrolled in the Adventist Mortality Study in 1960 and followed through 1985. Coffee consumption was divided into three levels: less than 1 cup per day, 1-2 cups per day, and greater than or equal to 3 cups per day. Approximately one third of the subjects did not drink coffee. Cause-specific mortality rates were compared using survival analysis including Cox's proportional hazard model, and controlling for potential confounders such as body mass index, heart disease and hypertension at baseline, race, physical activity, marital status, educational level, smoking history, and dietary pattern. Inclusion of interaction terms between coffee consumption and attained age as time-dependent covariates allowed the hazard ratio to vary with age. Univariate analyses showed a statistically significant association (p less than 0.05) for coffee consumption and mortality for most endpoints. Multivariate analyses showed a small but statistically significant association between coffee consumption and mortality from ischemic heart disease, other cardiovascular diseases, all cardiovascular diseases, and all causes of death. For the major causes of death, the hazard ratios decreased from about 2.5 at 30 years of age to 1.0 around 95 years of age. These results indicate that abstinence from coffee leads to compression of mortality rather than an increase in lifespan. PMID- 1619454 TI - The role of health care providers and significant others in evaluating the quality of life of patients with chronic disease: a review. AB - The use of proxy raters of patients' quality of life has been suggested as a means of facilitating the factoring of quality-of-life considerations explicitly into the medical decision-making process and of resolving the problem of missing data in longitudinal quality-of-life investigations. This review addresses two questions related to the potential role of such proxy raters in clinical research and practice: (1) to what extent are health care providers and lay individuals involved in the care of patients ("significant others") able to assess accurately the quality of life of patients with chronic disease? and (2) under what conditions, if any, is inclusion of such proxy ratings in quality-of-life investigations warranted? Although the extant literature yields few unequivocal findings, a number of clear trends can be identified: (i) health care providers and significant others tend, in general, to underestimate patients' quality of life; (ii) health care providers and significant others appear to evaluate patients' quality of life with a comparable degree of (in)accuracy; (iii) health care providers tend to underrate the pain intensity of their patients; (iv) proxy ratings appear to be more accurate when the information sought is concrete and observable; and (v) while significant others' ratings tend to be more accurate when they live in close proximity to the patient, they can also be biased by the caregiving function of the rater. There is need for more methodologically sound studies that: (a) incorporate head-to-head comparisons of health care providers and significant others as proxy raters; (b) employ well-validated quality-of-life measures; and (3) employ a longitudinal design in order to examine the effect of changes in patients' health status over time on the ability of proxies to provide valid quality-of-life assessments. PMID- 1619455 TI - The relationship between multiparity and lipoprotein levels in older women. AB - The relation between multiparity and lipid and lipoprotein levels was examined in a sample of 1275 Rancho Bernardo women aged 50-89. Number of pregnancies ranged from 0 to 13 with a mean of 2.1. Pregnancy was unrelated to high density lipoprotein cholesterol level in women with 4 or fewer pregnancies, but women with 5 or more pregnancies had significantly lower levels both before and after adjustment for age, obesity, diabetes, alcohol and cigarette consumption, exercise and estrogen use. After multiple regression analysis, women with 5 or more pregnancies had high density lipoprotein levels that were 4.9 mg/dl lower than women with 4 or fewer pregnancies. No differences in total cholesterol, low density lipoprotein cholesterol or triglyceride levels were observed by number of pregnancies. If confirmed by others, these results suggest that one factor mediating the previously reported relationship between multiparity and cardiovascular disease may be a decreased level of high density lipoprotein cholesterol. PMID- 1619456 TI - Variance imputation for overviews of clinical trials with continuous response. AB - Overviews of clinical trials are an efficient and important means of summarizing information about a particular scientific area. When the outcome is a continuous variable, both treatment effect and variance estimates are required to construct a confidence interval for the overall treatment effect. Often, only partial information about the variance is provided in the publication of the clinical trial. This paper provides heuristic suggestions for variance imputation based on partial variance information. Both pretest-posttest (parallel groups) and crossover designs are considered. A key idea is to use separate sources of incomplete information to help choose a better variance estimate. The imputation suggestions are illustrated with a data set. PMID- 1619457 TI - Social and environmental factors and dysthymic disorder in old age. AB - This community-based epidemiological survey is concerned with relationships between social and environmental factors and dysthymic disorder (long-lasting depression according to the DSM-III classification) in a Finnish population aged 60 years or over. A greater proportion of dysthymic than non-depressed men had retired and did not work at all. The occurrence of dysthymic disorders in both men and women was related to retirement because of sickness rather than age, a small number of rooms in their homes, lack of intimate friendships and the occurrence of many long-standing and current social stress factors. The dysthymic women had lived at their present place of residence for a shorter period than had the non-depressed women. A positive association of dysthymic disorders with moving house due to poor health and living in institutions was also found in the men, and with a low number of hobbies and poor social participation in the women. In addition, the dysthymic women felt their relationships with their spouse, children, daughters-in-law and friends to be more distant than did their non depressed counterparts. The dysthymic women also felt that elderly people were not appreciated. The log-linear models showed three interactions for the dysthymic men and six for the dysthymic women. The dysthymic persons reported a significantly larger number of detrimental events of an interpersonal nature than did the non-depressed persons. PMID- 1619458 TI - Sources of interobserver variation in histopathological grading of cervical dysplasia. AB - The present study aimed to assess where the interobserver variation in grading cervical dysplasia stems from. Four experienced pathologists examined 93 histological slides, after they agreed on which morphological characteristics should be considered relevant for grading. They scored 6 morphological characteristics for each slide and assigned it to a degree of dysplasia. Compared to a previous study, the interobserver variation showed a statistically significant improvement: the weighted group kappa value increased from 0.55 to 0.69. For the scores of the individual characteristics considerable interobserver variation was observed: weighted group kappa values ranged from 0.28 to 0.49. The pathologists slightly differed in which characteristics they considered most important for their grading. The agreement on the degree of dysplasia turned out to be better than the agreement on the morphological characteristics on which this diagnosis is based. In the discussion, a few explanations for this paradoxical finding are put forward. PMID- 1619459 TI - The accuracy of self and informant ratings of physical functional capacity in the elderly. AB - To compare the accuracy of self-ratings with informant-ratings of physical functional capacity in the elderly, 150 elderly patients attending a geriatric day hospital (GDH) and their formal and informal community carers were administered a questionnaire about their ability to perform activities of daily living (ADL). Direct observation of the patients' performance by therapists at the GDH was used as a standard, after the reliability and validity of this approach had been evaluated. Self-ratings were shown to be more accurate and less biased than informant-ratings, both for individual ADL and overall functional capacity. The accuracy of all ratings tended to be greater for less complex or physically demanding ADL, and informants tended to consistently underestimate functional capacity. The concurrent validity of the adapted Barthel Index in a self-report format was also demonstrated. Wherever possible, information concerning the physical functional capacity of an elderly subject should in the first instance be sought from the subject himself, as the quality of such information may be superior to that of his carers. PMID- 1619460 TI - When philosophers shoot from the hip. PMID- 1619461 TI - Abstract expression. PMID- 1619462 TI - Body mass and breast cancer. PMID- 1619464 TI - Age, dietary selenium and quantity of 7,12-dimethylbenz(a)anthracene influence the in vivo occurrence of rat mammary DNA adducts. AB - The present studies determined the impact of age, dietary selenium and 7,12 dimethylbenz(a)anthracene (DMBA) dosage on the occurrence of DMBA-DNA adducts in rat mammary tissue. Diets formulated to contain selenium, as sodium selenite, at 0.1 (control) or 2.0 mg/kg were fed for 2 wk before DMBA treatment. Food intake and weight gain were not influenced by selenium intake. Anti- and syn-dihydrodiol epoxide adducts reached maximum binding by 24 and 36 h, respectively, after treatment with DMBA. Consumption of the diet containing 2.0 mg Se/kg inhibited the appearance of both anti- and syn-adducts by approximately 50% compared with controls. The occurrence of DMBA-DNA adducts correlated with a dosage of DMBA from 5 to 50 mg/kg body wt (r greater than or equal to 0.95). The ability of supplemental selenite to lower DMBA binding to mammary cell DNA increased as the quantity of the carcinogen administered increased. DMBA-DNA binding was found to increase with the increasing age of the rat. Nevertheless, dietary selenium supplementation was effective in reducing DMBA binding to DNA in all ages examined. These data confirmed the ability of dietary selenium to inhibit the in vivo metabolism of DMBA under a variety of conditions. PMID- 1619463 TI - Dietary calcium modifies concentrations of lead and other metals and renal calbindin in rats. AB - We studied the effects of dietary calcium on kidney, femur, testis, liver, heart and brain concentrations of lead, magnesium, iron, copper, calcium and zinc in rats exposed to lead for 1 y. Renal levels of the 28,000 Da, vitamin D-dependent, calcium-binding protein calbindin-D28K were also measured. Seventy-two weanling male Sprague-Dawley rats were randomly assigned to one of nine treatment groups. Rats were fed diets containing 0.1, 0.5 or 2.5% Ca for 52 wk and were simultaneously given either 0, 50 or 100 mg lead/L in their drinking water. Rats fed the 0.1% Ca diet had organ lead concentrations that were two- to 20-fold greater than the corresponding animals fed 0.5% Ca. Rats fed diets containing 2.5% Ca had the lowest organ lead concentrations. Despite substantial effects of diet Ca on organ lead concentrations, Ca did not significantly influence concentrations of most other divalent metals studied with the exception of kidney calcium and magnesium, testis iron, plasma ionic calcium and magnesium, and several femur metals. Kidney calcium concentrations were lower in rats fed 2.5% Ca diets than in those fed 0.1 or 0.5% Ca diets. For rats not given lead, renal calbindin concentrations were highest in rats fed 0.1% Ca, and lowest in rats fed 2.5% Ca. Lead inhibited an increase in renal calbindin in the rats fed 0.1% Ca, but paradoxically increased renal calbindin levels in animals fed 2.5% Ca. PMID- 1619465 TI - Protein deficiency impairs erythropoiesis in rats by reducing serum erythropoietin concentration and the population size of erythroid precursor cells. AB - Erythropoietin (EPO), a glycoprotein produced mainly by the kidney, is the major physiological regulator of erythropoiesis. We developed a sensitive and rapid ELISA for measurement of rat serum EPO with two monoclonal antibodies that recognize different epitopes. To understand the mechanism by which erythropoiesis is impaired in rats deficient in dietary protein, we investigated the levels of the immunoreactive EPO (iEPO) in serums and erythroid precursor cells in hemopoietic tissues during protein deprivation. The iEPO level of 32-d-old rats fed a protein-free diet was lowered to one-third that of rats fed 20% casein at 6 h after protein deprivation began. Protein deprivation decreased the number of EPO-responsive cells in spleen. These results indicate that the impairment of erythropoiesis during protein deficiency is caused by the decrease in serum EPO and the subsequent reduction of the population size of erythroid precursor cells in spleen. PMID- 1619466 TI - Cobalt-vitamin B-12 deficiency decreases methionine synthase activity and phospholipid methylation in sheep. AB - Two groups of lambs were fed either a Co-deficient or a Co-sufficient whole barley-based diet for 28 wk to induce a severe Co-vitamin B-12 deficiency. Holo and apo methionine synthase activities were significantly lower in the liver, kidney and spinal cord of Co-deficient animals compared with controls. Neither form of this enzyme in the brain was affected by Co deficiency. The ratio of the tissue concentrations of S-adenosyl methionine to S-adenosyl homocysteine was significantly lower only in the liver of Co-deficient animals, suggesting that the activity of hepatic SAM-dependent methyltransferase enzymes would be impaired. Measurements of tissue concentrations of phosphatidyl choline and phosphatidyl ethanolamine revealed lower concentrations of phosphatidyl choline and a lower phosphatidyl choline:phosphatidyl ethanolamine ratio in both liver and brain of the Co-deficient animals. The latter finding occurred in the absence of changes in either methionine synthase activity or the methylation ratio and may result from impaired availability of hepatic phosphatidyl choline for transport into the brain. PMID- 1619467 TI - Methyl group metabolism in the pancreas of folate-deficient rats. AB - Several studies have suggested that the metabolism of one-carbon compounds may have a special role in the function of the exocrine pancreas. An amino acid defined diet was used to produce folate deficiency in a group of male rats. These rats were compared with a group of rats pair-fed the same diet supplemented with adequate folate and with a third group fed the folate-supplemented diet with ad libitum access. Pancreatic folate concentrations were already severely depleted after 4 wk of feeding the deficient diet (0.95 +/- 0.10, 5.81 +/- 0.29 and 4.58 +/- 0.30 nmol/g for the deficient, pair-fed control and ad libitum-fed control groups, respectively). The level of folate present in the pancreas of nondeficient animals was second only to that reported for liver. Urinary amylase excretion by animals in the deficient group was higher than that by the other groups (245.5 +/- 21.9, compared with 181.9 +/- 14.5 and 195.3 +/- 10.9 units/mg creatinine for the deficient, pair-fed control and ad libitum-fed control groups, respectively) after 4 wk. The ratio of S-adenosylmethionine to S adenosylhomocysteine was 18.6 +/- 1.6 and 14.5 +/- 1.0 after 4 wk for the ad libitum-fed control and pair-fed control groups, respectively, but was significantly lower at 6.3 +/- 1.1 for the deficient group. These results indicate a profound effect of folate deficiency upon methyl group metabolism of the pancreas and suggest that this may result in decreased pancreatic function. PMID- 1619468 TI - Dietary cholesterol and type of fat differentially affect cholesterol metabolism and atherosclerosis in baboons. AB - This study was designed to determine the differences in cholesterol metabolism due to dietary cholesterol and type of fat in adult baboons. From weaning at 16 wk to 7-8 y of age, 80 baboons were fed one of four diets: high cholesterol (0.24 mg/kJ) or low cholesterol (0.0024 mg/kJ) with 40% of energy from saturated fat [polyunsaturated/saturated fatty acid ratio (P/S) = 0.37] or unsaturated fat (P/S = 2.1). High cholesterol and saturated fat independently raised serum lipoprotein and apolipoprotein concentrations to about the same extent. The liver cholesterol concentration of baboons fed high cholesterol diets was 23% higher than that of baboons fed low cholesterol. High dietary cholesterol also increased bile cholesterol concentration by 25%, the neutral steroid excretion rate by 66% and the bile acid excretion rate by 30%. With feeding of saturated fat, compared with unsaturated fat, liver cholesterol was 24% lower, bile cholesterol 26% lower and the neutral steroid excretion rate 12% lower. Dietary cholesterol greatly suppressed whole-body cholesterol synthesis, but type of fat did not affect cholesterol synthesis rate. These results suggest that dietary cholesterol and saturated fat increase plasma lipoprotein concentrations through different physiological mechanisms. PMID- 1619469 TI - Iron nutrition does not account for the hemoglobin differences between blacks and whites. AB - Many researchers have reported lower hemoglobin concentrations in blacks than in whites, but the reason for this difference is unknown. Data for 2515 persons (in 3-12 y and 18-45 y age groups) from the Second National Health and Nutrition Examination Survey (NHANES II) were evaluated to investigate the roles of iron intake and biochemical iron status indicators in explaining black and white differences in hemoglobin concentration. Dietary iron intake was estimated from one 24-h food recall, and hemoglobin, serum ferritin, transferrin saturation and erythrocyte protoporphyrin were measured by standard laboratory methods. Hemoglobin levels were substantially lower in black children (120.3 g/L) than in white children (126.8 g/L). Hemoglobin concentrations were also lower in black women (128.4 g/L) than in white women (133.9 g/L), and in black men (144.8 g/L) than in white men (153.2 g/L). Blacks had lower hemoglobin concentration than whites at most levels of dietary iron intake, serum ferritin, transferrin saturation and erythrocyte protoporphyrin. Despite their lower hemoglobin levels, blacks had higher serum ferritin levels than whites. These results suggest that the difference in hemoglobin concentrations between blacks and whites in the United States is the result of factors other than iron intake and iron status. More specific investigations of both the genetic and environmental determinants of iron utilization in blacks are needed. PMID- 1619470 TI - A method for estimating the available energy of incompletely digested carbohydrates in rats. AB - We developed a method to estimate the available energy from carbohydrates that are unavailable or partially unavailable through direct digestion and absorption. Radiolabeled bacterial and plant cellulose and polydextrose were administered orally to germfree and conventional rats. Label in breath, feces, intestinal contents and carcass were determined with excellent total recovery of the administered label. Comparison of these measurements in germfree and conventional rats was used to calculate the energy directly available by digestion and that available only after fermentation. Although the method overestimates available energy because of the more efficient digestive metabolism of the germfree rat, it provides a reliable, maximum energy value based upon fewer assumptions than previous methods. In conventional rats, 65% of the administered cellulose and 54% of the administered polydextrose were recovered in feces. In conventional rats, appreciable amounts of cellulose were fermented and an available energy value of 3.5 kJ/g was calculated. Calculation of the total availability of polydextrose, taking into account the direct absorption of small amounts of monomers present and the efficiency of fermentation, indicates an available energy value of 4.7 kJ/g. PMID- 1619471 TI - Mitotic activity in mice is suppressed by energy restriction-induced torpor. AB - We monitored core body temperature by telemetry in energy-restricted (201 kJ/wk) and control (397 kJ/wk) C57BL/6 and SHN/C3H F1 mice to determine whether torpor may be involved in the suppression of mitotic activities resulting from energy restriction. The energy restriction regimen employed inhibited the development of cancer and greatly extended longevity in both these mouse strains. Male and female C57BL/6 mice subjected to energy restriction from 4 wk of age and tested at 3 mo of age became torporific (body temperature less than 31 degrees C) at ambient air temperatures of 20-22 degrees C, whereas control animals stayed euthermic (greater than 35 degrees C). Energy restriction also induced torpor in 3- and 13-mo-old SHN/C3H F1 female mice, whereas 3-, 13- and 24-mo-old control mice were euthermic. Energy restriction decreased mitotic activities to approximately 30% of control values in both jejunum and epidermis in 3-mo-old female C57BL/6 mice maintained at 20-22 degrees C. However, this suppression of mitotic activities was antagonized by housing the energy-restricted mice at 30 degrees C for 2 wk, indicating that torpor plays a substantial role in suppressing mitotic activities in energy-restricted mice. PMID- 1619473 TI - Retention of 14C label is lower in old than in young Wistar rats after oral dosing with [14C]pyridoxine. AB - Ten young (6-mo-old) and ten old (31-mo-old) male Wistar rats fed a purified diet (250 g casein and 6 mg pyridoxine.HCl per kg) from weaning were given either a single oral dose or five repeated oral doses of 14C-labeled pyridoxine. At various times after dosing animals of each age group were killed. Absorption of orally dosed [14C]pyridoxine.HCl was not found to be different between young and old rats. Total body retention of 14C label administered was modestly but significantly lower in old than in young rats. However, distribution of 14C label over various tissues and among the various B-6 vitamers was similar. No significant age-related differences were observed in the biokinetic parameters derived from urinary excretion data. Contrary to the findings for 14C label distribution, age-related differences were observed for absolute level of tissue 14C-labeled vitamers. The lower [14C]pyridoxal-5'-phosphate content in liver and muscle, and [14C]pyridoxamine-5'-phosphate content in liver, of old animals indicated an age-related difference in liver and muscle vitamin B-6 disposition. In both young and old rats, and in both liver and muscle tissue, pyridoxamine-5' phosphate was observed to be a faster-exchanging tissue vitamin B-6 pool than pyridoxal-5'-phosphate. PMID- 1619474 TI - Dietary arginine deficiency alters flux of glutamine and urea cycle intermediates across the portal-drained viscera and liver of rats. AB - The effect of an arginine-deficient diet on net flux of amino acids across the portal-drained viscera and across the liver was studied in rats. Blood was obtained after food deprivation and 1 and 2 h after a meal of a 1.0% arginine control diet or an arginine-deficient diet containing 3.4% glutamate. The arginine-deficient diet decreased net portal-drained viscera flux of arginine and increased net portal-drained viscera flux of ornithine and proline. However, net portal-drained viscera flux of citrulline (0.35 +/- 0.05 mumol/min) was not influenced by diet; of this rate, 46% (0.16 mumol/min) bypassed the liver and was available for extrahepatic arginine synthesis. However, rats continued to exhibit signs of arginine deficiency such as decreased blood arginine concentrations (by 28%) and increased orotic acid excretion (90-fold). Arterial blood glutamine concentration was 25% higher in rats fed the arginine-deficient diet. In the fed state, net hepatic flux of glutamine was elevated from 0.15 (control) to 1.39 mumol/min, indicating that the liver was a major source of the increased blood glutamine concentrations. Increased production of hepatic glutamine and orotic acid may help rats compensate for dietary arginine deficiency, whereas splanchnic output of citrulline was not increased with dietary arginine deficiency even with a substantial dietary supply of glutamate. PMID- 1619472 TI - Sodium-dependent transport of riboflavin in brush border membrane vesicles of rat small intestine is an electrogenic process. AB - Transport of riboflavin across the intestinal brush border membrane in rats was studied using the brush border membrane vesicle technique. Uptake of riboflavin into the membrane vesicles was predominantly the result of transport into an osmotically reactive space. Binding of the substrate to the membrane surface increased as a function of time and with lowering of the incubation buffer pH. The transport of riboflavin at low substrate concentrations was carrier mediated and Na+, but not K+, dependent with a distinct overshoot phenomenon. Uptake as a function of substrate concentration revealed dual transport characteristics in the presence of a Na+ gradient but linearity in the presence of a K+ gradient. The apparent Km value of the saturable, carrier-mediated and Na(+)-dependent component was calculated by two independent methods to be 0.25 or 0.38 mumol/L. Because uptake of riboflavin into brush border membrane vesicles in the presence of a Na+ gradient was increased by a valinomycin-induced K(+)-diffusion potential and by sodium thiocyanate vs. NaCl (intravesicular negative membrane potential), riboflavin transport is most likely an electrogenic process. The Na(+)-dependent riboflavin uptake into the vesicles was inhibited by structural analogues at low substrate concentrations only and increased by a low buffer pH. PMID- 1619475 TI - Energy expenditure in rats maintained with intravenous or intragastric infusion of total parenteral nutrition solutions containing medium- or long-chain triglyceride emulsions. AB - Energy expenditure was determined in male Fischer 344 rats (235-246 g) fed by intravenous (IV) or intragastric (IG) infusion with total parenteral nutrition solutions providing 65% of nonprotein energy as fat from long-chain triglyceride (LCT) or a 3:1 admixture of medium-chain triglyceride (MCT) and LCT emulsions. Respiratory gas exchange and somatomotor activity were assessed continuously for 24 h during d 5 and 11 of infusion feeding. The MCT infusion resulted in one third the weight gain noted with LCT infusion (MCT, 10 +/- 2 g/14 d; LCT, 32 +/- 4 g/14 d; P less than 0.0001). Insulin concentration was 60% higher with IV than with IG infusion and approximately 100% higher with IV-MCT than with IG-MCT or LCT infusion (P less than 0.05). Rats receiving IV infusion of MCT displayed similar levels of motor activity but 8-13% greater daily energy expenditure (kJ.kg-0.75.kJ intake-1) than rats receiving IG-MCT or LCT infusion (P less than 0.05). The MCT infusion also resulted in an elevation in respiratory quotient after cessation of nutrient infusion (MCT, 0.87-0.92; LCT, 0.83-0.85; P less than 0.05). Total and resting energy expenditure decreased approximately 13% from 5 to 11 d of infusion feeding. The lower weight gain and greater energy expenditure seen with MCT- compared with LCT-supplemented total parenteral nutrition may be mediated by higher insulin concentrations. PMID- 1619476 TI - Biotin deficiency in rats: disturbances of leucine metabolism are detectable early. AB - 3-Methylcrotonyl-CoA originates from catabolism of leucine and is normally metabolized to acetyl-CoA. However, in biotin deficiency, reduced hepatic activity of the biotin-dependent enzyme methylcrotonyl-CoA carboxylase causes the enzyme's substrate 3-methylcrotonyl-CoA to be shunted via an alternate pathway to 3-hydroxyisovaleric acid (3-HIA), which is excreted at increased rates in the urine. In a previous study, unequivocal separation in 3-HIA excretion rates between biotin-deficient and control animals was not apparent until d 35 of feeding a diet that induced biotin deficiency. The present study tested the hypothesis that abnormal 3-HIA excretion could be detected earlier in the course of biotin deficiency if 3-HIA were more accurately measured using a method that incorporated an improved extraction regimen, deuterated 3-HIA as internal standard, and unlabeled 3-HIA as external standard. Biotin deficiency was induced in rats by feeding a diet containing avidin; control rats received the same diet and biotin injections. With the more accurate method, unequivocal detection of deficiency was possible in all deficient rats by d 16. This study provides evidence that, in rats, reduction of analytical error allows earlier detection of biotin deficiency and that disturbances of leucine metabolism occur earlier than previously appreciated. PMID- 1619477 TI - Oleic acid (18:1) in plasma, liver and brain myelin lipid of piglets fed from birth with formulas differing in 18:1 content. AB - Recent studies have shown reduced 18:1 fatty acids in brain total lipid of piglets fed formula with 17% 18:1 fatty acids rather than sow milk providing 37% 18:1. Because 18:1 is a major fatty acid in brain myelin lipid and is rapidly deposited during myelination, it is important to know if this reflects deposition of myelin lipid containing reduced 18:1 and/or delayed myelination, or is related to changes in other brain membranes. Therefore, these studies determined the myelin total lipid, phosphatidylethanolamine and plasma and liver phospholipid fatty acids in piglets fed from birth to 15 d with formula containing (g/100 g fatty acids): 18:1, 17 and 18:3(n-3), 0.8; 18:1, 38 and 18:3(n-3), 0.6 fatty acids; or 18:1, 40 and 18:3(n-3), 4; or sow milk. Different levels of formula 18:3(n-3) fatty acids were studied because of the known effect of essential fatty acid deficiency on myelination. The brain 2',3'-cyclic nucleotide 3' phosphohydrolase (CNPase) activity and cerebroside concentration were also determined and used as indicators of myelination. Piglets fed the low 18:1 formula had lower 18:1 fatty acids in their plasma and liver phospholipid than sow milk-fed piglets. Formula providing a similar level of 18:1 to sow milk resulted in higher 18:1 fatty acids in the piglet plasma and liver phospholipid than in the sow milk-fed piglets. The brain myelin monoenoic fatty acids, CNPase activity and cerebroside concentration were similar in sow milk- and formula-fed piglets, irrespective of the formula 18:1 or 18:3(n-3) content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619478 TI - Type I iodothyronine deiodinase activity after high selenium intake, and relations between selenium and iodine metabolism in rats. AB - Type I iodothyronine deiodinase (I-D), which catalyzes the production of the thyroid hormone 3,3',5-triiodothyronine from thyroxine, has recently been identified as a selenoenzyme. It is therefore of interest to investigate the relationships between selenium and iodine metabolism. In the livers of Se deficient rats I-D activity was inhibited; the production of 3,3',5 triiodothyronine and 3,3'-diiodothyronine from added thyroxine was decreased by greater than 95% relative to Se-adequate controls. The hepatic I-D activity was also reduced in rats fed a diet with a low iodine concentration. Unaltered glutathione peroxidase activities in liver and plasma of these rats suggest, however, that with normal Se intake this metabolic pathway of Se is not affected by iodine depletion. When rats were administered 75Se-labeled selenium at levels equal to the amounts ingested from diets with Se concentrations of 0.3 or 2 mg Se/kg, greater Se concentrations were found in the thyroid and liver of the animals receiving the higher dosage. The thyroidal 3,3',5-triiodothyronine and thyroxine concentrations, however, were comparable in rats fed diets with 0.3 mg Se/kg diet as selenite and 2 mg Se/kg as selenite or L-selenomethionine. The measurement of the hepatic I-D and glutathione peroxidase activities in these animals showed that excessive Se supply does not elevate the activities of the two enzymes but might even have the opposite effect. At high Se intake tissue Se concentration cannot therefore be used as indicator of the selenoenzyme activities. PMID- 1619479 TI - Copper deficiency alters vasodilation in the rat cremaster muscle microcirculation. AB - The effects of copper deficiency on smooth muscle relaxation were studied in the cremaster muscle microcirculation. Male Sprague-Dawley rats were fed either a copper-adequate diet (CuA, 5 micrograms copper/g diet) or copper-deficient diet (CuD, no added copper) for 17-27 d before experimentation. In vivo television microscopy was used to quantify agonist-induced diameter changes in third-order arterioles. Endothelium-dependent relaxation, which is hypothesized to be mediated by nitric oxide, was attenuated by copper deficiency. Both receptor (acetylcholine, 10(-7) to 10(-4) mol/L) and nonreceptor (calcium ionophore A23187, 10(-8) to 10(-7) mol/L) relaxation was decreased. Nitric oxide-mediated dilation, which was endothelium-independent (10(-7) to 10(-5) mol/L sodium nitroprusside), was also attenuated by copper deficiency. Maximal responses were as follows: for acetylcholine, 136 +/- 16% CuA vs. 45 +/- 15% CuD; for A23187, 104 +/- 16% CuA vs. 21 +/- 11% CuD; and for nitroprusside, 125 +/- 12% CuA vs. 46 +/- 13% CuD. There was no difference in microvascular dilation between groups treated with 10(-6) to 10(-4) mol/L of the phosphodiesterase inhibitor papaverine (e.g., CuA 109 +/- 11% vs. CuD 133 +/- 21% with 10(-4) mol/L). These results suggest that copper deficiency inhibits the nitric oxide-mediated mechanism of vascular smooth muscle relaxation without altering the capacity of the smooth muscle to relax. We suggest that copper deficiency either decreases nitric oxide radical availability or disrupts the nitric oxide-guanylate cyclase interaction. PMID- 1619480 TI - Modification of the clastogenic activity of X-ray and 6-mercaptopurine in mice by prefeeding with vitamins C and E. AB - The effect of a 30-d pretreatment with vitamin C (L-ascorbic acid) in the drinking water and vitamin E (all-rac-alpha-tocopherol) in the diet on the clastogenic activity induced by X-rays and 6-mercaptopurine was investigated in female ICR/Jcl mice by the bone-marrow micronucleus test. Prefeeding with vitamin E-deficient diets led to a significant decrease in serum vitamin E concentration and to an enhancement of micronucleus formation by X-rays in bone marrow cells. Although dietary supplementation with vitamin E significantly increased the vitamin E concentration in serum, it did not affect the frequency of X-ray induced micronuclei. Treatment with a high level of vitamin C in drinking water was effective in protecting against micronucleus formation by X-rays. The increase in micronucleus frequency in the vitamin E-deficient mice compared with the mice fed vitamin E-normal diets was no longer observed when a high level of vitamin C in drinking water was given simultaneously. The most efficient protective action against X-rays was observed when vitamin E-supplemented diets and a high level of vitamin C in drinking water were used together as a pretreatment. Any combination of the vitamins did not affect the micronucleus induction by 6-mercaptopurine. PMID- 1619481 TI - Cardiac ultrastructural and electrophysiological abnormalities in postweanling copper-restricted and copper-repleted rats in the absence of hypertrophy. AB - Cardiac ultrastructural and functional characteristics were determined in copper depleted and copper-repleted rats. Male weanling rats were randomized into five groups that were fed either copper-adequate or copper-deficient diets. After 5 wk, one group fed each diet was studied to obtain baseline values. At this time, one copper-adequate postweanling group continued to receive the adequate diet as control, one deficient postweanling group was fed the adequate diet to evaluate the effect of copper repletion and one postweanling adequate group was fed the deficient diet to evaluate copper depletion in relatively older rats. These dietary treatments were continued for six additional weeks. Copper-depleted rats of both ages exhibited significant cardiac ultrastructural pathology and electrocardiogram abnormalities and the postweanling copper-depleted rats exhibited these abnormalities in the absence of hypertrophy and anemia. Increased mitochondrial volume density, disarranged cristae, and nonaligned myofibrils with disturbances at Z-bands were displayed. Additionally, all copper-depleted rats demonstrated fragmented basal laminae at capillary-myocyte interface. Increased QRS amplitude and notching and greater QT intervals were displayed. Copper repleted rats exhibited some, but not total, reversal of these abnormalities. These results suggest that capillary-myocyte interface changes may play an important role in the developing pathology of copper depletion. PMID- 1619482 TI - Zinc nutritional status modulates the response of 1,25-dihydroxycholecalciferol to calcium depletion in rats. AB - Male Lewis rats (n = 27) were fed a nonpurified diet containing 0.9% calcium, 0.7% phosphorus, and 0.005% zinc until 8 wk of age. At this time rats were assigned randomly to one of two groups. Both groups were fed a low calcium, low zinc, purified diet (0.2% calcium, 0.4% phosphorus, less than 0.00007% zinc), but one group was fed 1.78 mg Zn/(animal.d). The zinc-replete animals were individually matched by weight to the zinc-depleted animals and pari-fed. Balances and plasma concentrations of zinc, calcium, and phosphorus and parathyroid hormone, 25 hydroxycholecalciferol [25(OH)D] and 1,25 dihydroxycholecalciferol [1,25(OH)2D] were determined at the start of calcium depletion and 2 wk later. Calcium and 25(OH)D levels were lower in both groups after calcium depletion. Dietary zinc had no significant effect on calcium or 25(OH)D levels. Phosphorus concentrations were lower after calcium depletion, but phosphorus concentration was higher in the zinc-depleted compared with the zinc replete group at the end of the experiment. 1,25(OH)2D increased in both groups, but was higher in the zinc-replete than the zinc-depleted group at the end of the experiment. Calcium and phosphorus balances were greater in the zinc-depleted group at the end of the experiment. We conclude zinc depletion diminishes the response of 1,25(OH)2D to calcium depletion in rats. The mechanism is unknown, but may involve nonhormonally mediated changes in gastrointestinal absorption of calcium and phosphorus or an affect of zinc on extraintestinal processes. PMID- 1619483 TI - Dietary sucrose but not starch promotes protein-induced differences in rates of VLDL secretion and plasma lipid concentrations in rats. AB - Casein instead of soybean protein in a low fat, cholesterol-free diet containing sucrose increases both lipid secretion by rat liver and plasma cholesterol concentration. Male rats were studied to determine whether dietary sucrose is a prerequisite for these protein-induced differences of lipid metabolism in vivo. After 6 wk of consuming either casein plus sucrose, soybean protein isolate plus sucrose, casein plus starch or soybean protein isolate plus starch (carbohydrate, 69 g/100 g diet; protein, 20 g/100 g diet) plasma lipids were measured. VLDL degradation was blocked by Triton WR-1339 and rates of lipid secretion were calculated from the observed linear increase in plasma levels with time. Plasma cholesterol concentrations and rates of secretion of VLDL cholesterol and triglycerides were 27, 47 and 34% higher, respectively, in animals fed casein plus sucrose compared with soybean protein plus sucrose. These differences were clearly diminished or absent when starch was the dietary carbohydrate. The data substantiate the finding that dietary sucrose but not dietary starch promotes a casein-induced increase in hepatic cholesterol secretion and thus contributes to casein-induced hypercholesterolemia in rats. On the contrary, differences of triglyceride secretion were not reflected in different plasma lipid concentrations. PMID- 1619484 TI - Low protein diets potentiate lithocholic acid-induced cholestasis in rats. AB - Earlier studies showed that low protein diets (LPD) reduce bile flow and bile acid secretion. We therefore examined the effect of LPD on lithocholic acid (LCA) induced intrahepatic cholestasis. Female Sprague-Dawley rats were fed LPD (8% casein) soon after weaning for 4 or 12 wk, and then were injected intravenously with a single dose of LCA (4 mumol/100 g body wt). Bile was collected for 30-min periods, and bile flow as well as biliary lipid secretory rates were measured. Bile acid metabolism was also studied and the results were compared with those obtained in rats fed an adequate protein diet (26% casein). The LPD produced significantly lower bile flow and bile acid secretion, which were attributed to a reduced bile acid pool and a reduction in synthesis. They also enhanced the LCA induced decline in bile flow, and rate of biliary output of total bile acids, phospholipids and cholesterol. The LPD were also associated with impaired LCA secretion in bile and increased retention in plasma and liver. Studies of LCA metabolism in rats fed a LPD indicated lower hepatic LCA hydroxylation, a greater percent contribution of glyco conjugates and lower levels of tauro conjugates. The present findings suggest that the reduced bile acid pool size, diminished LCA excretion and biotransformation to less toxic bile acids may explain the greater cholestasis in LPD-fed rats. PMID- 1619485 TI - Company-sponsored health exams. PMID- 1619486 TI - Working conditions. PMID- 1619487 TI - Excess cancer among white-collar workers in studies based on death certificates. PMID- 1619488 TI - Factors in job decisions. PMID- 1619489 TI - Preemployment drug screening. The epidemiologic issues. AB - Deciding to test applicants for employment for drugs raises complex, legal, moral, economic, and technical issues. However, we focus here on three epidemiologic issues germane to this decision. In one industry, the United States Postal Service, two recent studies suggest associations between positive preemployment drug screens and turnover, absenteeism, accidents, injuries, and discipline, but these associations are weaker than had been assumed. Cost-benefit analyses show that whether drug screening saves money depends both on the costs associated with adverse outcomes such as accidents and on the prevalence of drug use in the population screened. Finally, the predictive value of a positive drug screen also depends crucially on the prevalence of drug use. In populations with low prevalence of drug use, a large proportion of the positives may be false positives. PMID- 1619491 TI - Personal and job characteristics of musculoskeletal injuries in an industrial population. AB - A cross-sectional study was conducted of 10,350 full-time regular employees who worked at Shell Oil Company's manufacturing facilities between 1987 and 1989. Two hundred seventy-five employees with low-back and 456 with nonlow-back musculoskeletal injuries were compared with 8295 employees who did not have musculoskeletal injuries during this period. Based on morbidity data collected from a prospective health surveillance system, this study shows that estimated relative risks (RRs) for low-back injuries are significantly higher among smokers (RR = 1.54, P less than .01) and overweight persons (RR = 1.42, P less than .01). This observation is also true for nonlow-back musculoskeletal injury (RR = 1.23, P = .05 for smokers and RR = 1.53, P less than .01 for overweight persons). In addition, persons in potentially more physically demanding jobs (primarily maintenance job titles) had an increased RR for both low-back and nonlow-back musculoskeletal injuries (RR = 1.57, P less than .01 and RR = 1.35, P = .02, respectively). The findings of this study suggest that it may be possible to reduce the impact of musculoskeletal injury through implementation of an integrated injury prevention program. Such programs would include not only the traditional elements of job factors evaluation and modifications, employee education and training, and an overall increased attention to ergonomics but also medical counseling and support for personal fitness programs, workplace smoking cessation programs, and weight-reduction programs. PMID- 1619490 TI - Olfactory impairment after chronic occupational cadmium exposure. AB - Disorders of olfaction affect millions of Americans, but the extent to which occupational and environmental exposures contribute to these disorders is unknown. We examined 55 workers with chronic occupational exposure to cadmium fumes in a brazing operation. We estimated cadmium body burden using urinary cadmium levels and assessed cadmium-induced renal damage by urinary beta 2 microglobulin levels. We quantified olfactory function using a standardized test that measured two components of olfaction, butanol detection threshold and odor identification, and compared workers with a reference group. Forty-four percent of the cadmium-exposed workers were mildly hyposmic, and 13% were either moderately or severely hyposmic. In the reference group, 31% were mildly hyposmic, and the rest were normosmic. The workers with both high urinary cadmium levels and tubular proteinuria had the most significant olfactory dysfunction, with a selective defect in odor detection threshold. Our findings suggest that chronic occupational cadmium exposure sufficient to cause renal damage also is associated with impairment in olfactory function. PMID- 1619492 TI - Effects of aircraft noise on hearing and auditory pathway function of airport employees. AB - The effects of aircraft noise on hearing and auditory pathway function were studied in 112 airport employees, both by audiometry and brainstem auditory evoked potentials (BAEPs) to evaluate cochlear function and to verify the possibility of retrocochlear involvement. Employees were divided into five groups according to their daily jobs. Group A was made up of 23 maintenance workers, Group B of 20 firemen, Group C of 24 policemen, Group D of 34 airline ground staff, and Group E of 14 civil servants. The typical audiogram pattern of noise induced hearing loss (NIHL) was a dip at 3 or 4 kHz and moderate hearing loss in the frequency range of 6 to 8 kHz. The results of audiograms in this study revealed the prevalence rate of high-frequency loss in all employees was 41.9%. The incidences of NIHL were highest in the groups of maintenance workers (65.2%) and firemen (55.0%), who are almost continuously exposed to aircraft noise. As for the BAEPs, both click threshold and latencies showed that the impairment was most severe in the groups of maintenance workers and firemen. There was prolongation in central conduction time, shown mainly in intervals of I-V and III V. This suggests that involvement of the central auditory pathway, especially between the pons and midbrain, is present. In summary, the degree of auditory damage coincided with job patterns. Furthermore, damage of both peripheral cochlear organs and the central auditory pathway by high-frequency aircraft noise exposure was confirmed. PMID- 1619493 TI - Cobalt cardiomyopathy. A report of two cases from mineral assay laboratories and a review of the literature. AB - Two young men employed in the mineral assay industry developed non-inflammatory cardiomyopathy. By review of clinical findings, elicitation of occupational and environmental histories, work-site evaluations, and ascertainment of tissue cobalt levels, Nevada Public Health authorities confirmed these cases to be due to occupational cobalt exposure. Hair and heart cobalt levels were elevated for the cases, but control samples had no detectable cobalt. Excess ischemic heart disease mortality among cobalt-exposed workers may reflect misdiagnosis of cardiomyopathy. PMID- 1619494 TI - The core technology of work-site wellness. AB - Work-site wellness programming his evolved through four stages of development. This article proposes a core technology of work-site wellness programs comprised of 10 dimensions that organize and systematize the range of activities undertaken by such programs. These 10 dimensions address the following tasks: (1) establishing program policy, (2) assessing the health status of the work force, (3) linking the work site with service providers, (4) linking individual employees with services appropriate to their needs, (5) providing options for behavior change strategies and interventions, (6) engaging employees in these various interventions, (7) organizing work-sitewide activities to support health improvement, (8) reviewing and altering organizational policies to make the work environment more supportive of health, (9) routinely evaluating program process and changes in health risks, and (10) periodically assessing longer-term program results. Two future dimensions are described that require further evidence of impact. Arguments and evidence in support of each dimension are provided, including discussion on how activities within each dimension work together to produce maximum effectiveness, and how various dimensions relate to each other to make an effective overall program. PMID- 1619495 TI - Neuropsychologic and postural sway improvement after Ca(++)-EDTA chelation for mild lead intoxication. AB - Neuropsychologic and postural sway test performance improved following Ca(++) EDTA chelation in a bridge worker with persistent central nervous system (CNS) symptoms 2 years after an episode of subacute lead intoxication. This case highlights the value of these tests in verifying symptoms and documenting response to therapy. Persistent disabling CNS symptoms with objective neuropsychologic deficits was unexpected, given the borderline total body lead burden. PMID- 1619496 TI - Cost effectiveness of work-site cholesterol screening and intervention programs. AB - A study was conducted to evaluate the costs and cost effectiveness of behavioral interventions designed to reduce high serum cholesterol levels in a manufacturing population. A sample of 3202 employees participating in a screening was separated into four intervention groups and a control group. All four intervention groups received an educational program of varying length (1 or 3 months). Two of these groups also received incentives. A second screening was conducted after the interventions to determine effectiveness. The 1-month educational intervention with incentive and the 3-month educational intervention had the lowest costs per participant ($46.28 and $53.09, respectively) and costs per borderline high or high risk participant reducing cholesterol greater than 10% ($285.89 and $351.56) and the greatest effectiveness per dollar spent (0.60 and 0.62). The cost effectiveness analyses were affected by the impact of the intervention and participation rate. Sensitivity analyses showed that increasing participation had a greater impact on the less cost-effective interventions. PMID- 1619497 TI - Introduction to a structural basis for renal and vascular complications in diabetes and hypertension. AB - BACKGROUND: An understanding of the structural basis for cardiovascular and renal complications in diabetes and hypertension is critical to design-focused intervention strategies. HYPOTHESIS: The processes leading to vascular damage in the kidney and in the arteries in diabetes and hypertension appear to be characterized by hypertrophic/hyperplastic changes in a number of cell types (such as smooth muscle cells, fibroblasts, mesangial cells) and by excessive deposition of extracellular matrix material. Markers of cell growth/proliferation, such as Na(+)-H+ exchange, show increased activity in diabetic patients with renal disease and in patients with essential hypertension. Insulin resistance is a feature of arterial hypertension and diabetes and may contribute to renal and cardiovascular damage in these patients. A number of risk factors for cardiovascular disease cluster in the subset of diabetic patients prone to renal disease. These include dyslipidaemia, left ventricular hypertrophy and hypertension. It is postulated that a familial predisposition to renal and cardiovascular disease is the underlying reason for the susceptibility to the diabetic cardiorenal syndrome. CONCLUSION: In the management of diabetes and hypertension, it may prove possible to instigate preventive strategies by using therapeutic agents such as angiotensin converting enzyme inhibitors, which have the potential to interfere with the haemodynamic, growth and insulin sensitivity processes that contribute to vascular damage. PMID- 1619498 TI - What to treat? The structural basis for renal and vascular complications and hypertension, and the role of angiotensin converting enzyme inhibition. Symposium, 26th meeting of the European Association for the Study of Diabetes. Dublin, Ireland, 10 September 1991. PMID- 1619499 TI - Renal structure and function in insulin-dependent diabetes mellitus in man. AB - PURPOSE: To review renal pathological changes in diabetes, which include thickening of all renal extracellular basement membranes and the mesangial matrix and, to a lesser extent, mesangial cell expansion. CRITICAL RENAL LESIONS IN DIABETIC NEPHROPATHY: Two renal lesions appear critical in diabetic nephropathy. Mesangial expansion out of proportion to the size of the glomerulus is inversely related to proteinuria, hypertension and a declining glomerular filtration rate. Arteriolar hyalinosis is related to global glomerulosclerosis and both are correlated with the clinical features of nephropathy. By the time renal dysfunction is clinically detectable, these lesions tend to be advanced. Interstitial volume may be increased in insulin-dependent diabetes mellitus, particularly in areas containing sclerotic glomeruli or marked tubular atrophy. FUTURE RESEARCH: Longitudinal studies of renal structure and function and a simultaneous study of potential risk factors and pathways of injury are necessary to develop more refined predictors and clearer pathogenic concepts of this important diabetic complication. PMID- 1619500 TI - Micro-albuminuria and large vessel disease in diabetes. AB - BACKGROUND: Atherosclerosis is a major cause of morbidity and mortality in insulin-dependent diabetes mellitus. Recent studies have shown that albuminuria is a predictor of cardiovascular disease in these patients and there is a particularly high incidence of coronary heart disease in the early stages of albuminuria. AVAILABLE EVIDENCE: A number of established cardiovascular risk factors, such as elevated blood pressure, atherogenic changes in the plasma concentrations of lipids and lipoproteins, elevated plasma levels of fibrinogen and, probably, hyper-reactivity of platelets are present in patients with diabetic nephropathy. Further, albuminuria may be a marker of generalized disease in the vascular wall of small and large blood vessels. Findings of an elevated rate of transcapillary albumin escape, an elevated plasma concentration of von Willebrand's factor and impaired fibrinolytic capacity in early diabetic nephropathy support this hypothesis. CONCLUSION: The initial pathophysiological mechanisms involved in diabetic nephropathy are still hypothetical and largely unknown. PMID- 1619501 TI - The vascular endothelium in diabetes and hypertension. AB - PURPOSE: To review recent research into the function of endothelial cells in relation to diabetes and hypertension, and the implications for cardiovascular control. ENDOTHELIAL FUNCTIONS: Endothelial cells extract and inactive circulating hormones, convert inactive precursors into vasoactive products, and synthesize and secrete vasodilator and vasoconstrictor mediators, which also modify platelet function and cell growth. DIABETES: Abnormalities in endothelial cell morphology and function are recognized features of diabetes. Diminished endothelium-dependent relaxation and enhanced endothelium-dependent contraction have been described. HYPERTENSION: Similar defects in endothelial cell function have been demonstrated in animal and human hypertension. These might lead to increased vascular tone, vasospasm, platelet activation and atheroma. THERAPY: Certain drugs modify or mimic endothelium-derived mediators. Endothelial dysfunction may contribute to cardiovascular pathology, but the precise clinical and therapeutic significance of modifying endothelial function remains to be determined. PMID- 1619502 TI - Micro-albuminuria and the organ-damage concept in antihypertensive therapy for patients with insulin-dependent diabetes mellitus. AB - OBJECT OF TREATMENT: Antihypertensive treatment in hypertensive patients with insulin-dependent diabetes mellitus is intended to prevent long-term complications, particularly diabetic nephropathy. DIABETIC HYPERTENSIVES WITH ABNORMAL ALBUMINURIA: Antihypertensive therapy, particularly with angiotensin converting enzyme (ACE) inhibitors, typically produces a permanent reduction in the decline of the glomerular filtration rate (GFR) in diabetic patients with abnormal albuminuria. The rate of decline in the GFR during antihypertensive treatment is a well accepted end-point in diabetic renal disease. DIABETIC HYPERTENSIVES WITHOUT ABNORMAL ALBUMINURIA: In insulin-dependent diabetic patients with essential hypertension but with normal urinary albumin excretion there is no reduction in the GFR. Longitudinal studies have shown a fall in the GFR only in the presence of significantly increased urinary albumin excretion. ABNORMAL ALBUMINURIA AS A MARKER OF INCIPIENT NEPHROPATHY: Micro-albuminuria and proteinuria may be pathogenetic factors in the development of nephropathy, leading eventually to end-stage renal failure in diabetic patients. Measurements of micro-albuminuria and proteinuria, in addition to blood pressure recordings, might therefore be used as indications for initiating antihypertensive treatment. NEED TO MONITOR PATIENTS FOR ABNORMAL ALBUMINURIA: Transglomerular macromolecular traffic may produce mesangial damage, with subsequent glomerulopathy and diabetic nephropathy. Thus, close monitoring for micro-albuminuria and proteinuria is desirable in the management of diabetic hypertensive patients. PMID- 1619504 TI - Abstracts presented at the 14th Scientific Meeting of the International Society of Hypertension. 14-19 June 1992, Madrid, Spain. PMID- 1619503 TI - Potassium as a link between insulin and the renin-angiotensin-aldosterone system. AB - PURPOSE: To focus on the interactions between insulin secretion, glucose tolerance and insulin sensitivity on the one hand and the renin-angiotensin aldosterone system on the other. EFFECTS ON INSULIN: Insulin is a potent stimulus for hypokalaemia, sparing body potassium from urinary excretion by transporting it into cells. Potassium also appears to play a key role in the antinatriuretic effect of insulin. Insulin-induced hypokalaemia increases plasma renin and angiotensin II levels while decreasing the serum aldosterone concentration. In turn, the renin-angiotensin-aldosterone system affects glucose tolerance by modulating plasma potassium levels, which act as a stimulus for glucose-induced insulin release. EFFECTS OF ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITION: Interference with the renin-angiotensin-aldosterone system by ACE inhibition blunts the hypokalaemic response to insulin, thereby improving glucose-induced insulin release and oral glucose tolerance. ACE inhibition, however, does not cause major changes in insulin sensitivity. POTASSIUM AND BLOOD PRESSURE: Plasma potassium levels are inversely related to blood pressure, both in population surveys and in intervention studies. In addition, in patients with essential hypertension, the level of plasma potassium appears to predict the blood pressure response to ACE inhibition. SUMMARY: Potassium metabolism is an important link between carbohydrate metabolism and the renin-angiotensin-aldosterone system by way of a double-feedback mechanism. Through the potential effects on blood pressure control, plasma levels of potassium represent a link between insulin and blood pressure in humans. PMID- 1619505 TI - [Comparison of CT and MRI in diagnosis of parapharyngeal tumors]. AB - Recently, the usefulness of CT and MRI in diagnosing parapharyngeal tumors has been established. At the same time, several modalities for these imagings, i.e. plane and enhanced CT, T1, 2 weighted MRI and Gadolinium enhanced MRI, have been developed. We compared the image findings of 12 tumors involving the parapharyngeal space with their operative records. T1 was most suited to diagnosing the sites of origins of tumors because of its superior depiction of the internal carotid artery and parapharyngeal fat. Enhanced CT was also superior in depicting these structures, but in cases where the parapharyngeal fat was diminished, or the parapharyngeal fat had been invaded by malignant tumor, enhanced CT was inferior to T1. The spatial resolution of T2 was poor, T2 was thus not useful in diagnosing the sites of origins of tumors. Because tumor intensity tended to be similar to that of fat in Gadolinium enhanced MRI imaging, Gadolinium was not as useful as T1. In diagnosing the extents of tumors, we examined the depiction of both tumor-fat and tumor-muscle interfaces. With regard to the depiction of the tumor-fat interface, enhanced CT and T1 were most useful. In diagnosing the tumor-muscle interface, Gadolinium enhanced MRI was most suitable. The net result is that MRI is superior to CT. PMID- 1619506 TI - [On the postoperative mucocele of the maxillary sinus and its simulating cases. A clinical treatise]. AB - The postoperative mucocele of the maxillary sinus typically occurs after 11-15 years after the initial Caldwell-Luc operation with the complaints of swollen and painful cheek. Typical signs and symptoms will be divided into two groups, the one which is associated with expansive lesions and the other with pains along the various branches of the maxillary nerve. In the clinical set-ups, cases with the similar signs and symptoms, and yet lacking definite mucoceles, are often encountered. The present treatise will compare 86 definite cases and 27 simulating cases as to the history, signs and symptoms, various modalities of imaging (CT & MRI), and the possible causes leading to simulating cases. The age at onset, gender, affected side, and period after the initial sinus surgery all showed no differences between the two, i.e., definite and simulating cases. Among signs and symptoms, the definite case showed more of swelling-related matters whereas the simulating case more of pain-related except toothache. The past history of surgeries for the mucoceles on the similar sides to the present lesion is more often seen in the simulating case (64.3%) than in the definite case (18.3%). The findings by imagings in the simulating cases are as follows; obliterated sinus (25.0%), healthy, aerated postop. cavity (35.7%), postop. cavity with mucosal thickening (32.1%), and cyst-like aerated cavity (7.1%). The possible causes leading to the simulating cases are as follows; causes unknown (39.3%), recurrent infection in the postop. cavity (28.6%), dental origin (10.7%), atypical neuralgia (10.7%) and the case shortly after the proceeding sinus surgery (within 12 months, 10.7%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619508 TI - [Carbohydrate structure of glycoconjugate in the murine eustachian tube pharyngeal orifice]. AB - In this study, neuraminidase (sialidase) and 6 different lectins, wheat germ agglutinin (WGA), Limax flavus agglutinin (LFA), Sambucus nigra agglutinin (SNA), Maackia amurensis agglutinin (MAA), peanut agglutinin (PNA), and Amaranthin, were used to histochemically characterize the carbohydrate structure of glycoconjugate in the murine eustachian tube pharyngeal orifice. A microwave irradiation technique was used to reduce the incubation time and background staining. After neuraminidase treatment, WGA, LFA, MAA, Amaranthin, and PNA stained epithelial goblet cells, glandular mucous cells, cell surfaces, and the mucous blanket. Without neuraminidase treatment, SNA and PNA did not stain any secretory cells. These results revealed that sialoglycoconjugates in the murine eustachian tube pharyngeal orifice are produced from epithelial goblet cells and glandular mucous cells, are present on cell surfaces and within the mucous blanket, and that their terminal trisaccharide linkage appears to be the sequence Neu5Ac (alpha 2-3) Gal (beta 1-3) GalNAc. PMID- 1619507 TI - [Flow cytometric analysis of DNA ploidy in nasosinal papilloma]. AB - Using paraffin embedded specimens taken from 32 patients with histologically benign nasosinal papillomas, we conducted nuclear DNA analysis by flow cytometry and studied the biological degree of malignancy in this disease. Aneuploidy, which is frequently observed in malignant tumors was not seen in any of these nasosinal papilloma cases. Age did not affect either S+G2M % or polyploid %, two parameters that reflect cell proliferation capacity. Both parameters, S+G2M % and polyploid %, were higher in inverted papillomas which are more likely to become malignant than epithelial papillomas. In recurrent cases of nasosinal papilloma both S+G2M % and polyploid % were higher than in nonrecurrent cases. Moreover, the polyploid % was significantly different, supporting speculation that this can be used as a parameter for predicting recurrence of nasosinal papilloma. PMID- 1619509 TI - [Statistical survey of multiple primary cancers of the head and neck]. AB - The incidence and factors associated with multiple primary cancer were surveyed and analyzed from April 1978 through December 1990 in our clinic. Fifty-nine cases with multiple primary cancers were selected for study from among 579 cases with malignant head and neck region tumors. The cancers involved the larynx in 17 cases (8.4%), oral cavity in 14 (19.4%), oropharynx in 13 (41.9%), hypopharynx in 7 (8.0%) and nasal cavity or paranasal sinus in 7 (8.0%). Twenty-one cases (35.6%) arose synchronously within one year. From our observations, heavy drinking and smoking were most strongly suspected to be risk factors for induction of malignancy. Most multiple primary cancers in the head and neck region were observed to coexistent in a "so called multicentric zone" consisting of the oral area, pharyngeal area, larynx, esophagus, stomach, and tracheobronchial tree. To avoid overlooking concealed cancer in the multicentric zone, upper gastro-intestinal endoscopy, bronchial endoscopy, chest X-ray and sputum examination should be performed for screening of patients with head and neck malignancies. PMID- 1619510 TI - [Quantitative analysis of cholesteatoma using high resolution computed tomography]. AB - Seventy-three cases of adult cholesteatoma, including 52 cases with pars flaccida type cholesteatoma and 21 with pars tensa type cholesteatoma, were examined using high resolution computed tomography, in both axial (lateral semicircular canal plane) and coronal sections (cochlear, vestibular and antral plane). These cases were classified into two subtypes according with the presence of extension of cholesteatoma into the antrum. Sixty cases with chronic otitis media with central perforation (COM) were also examined as controls. The various locations of the middle ear cavity were measured in term of size with comparisons among pars flaccida type cholesteatoma, pars tensa type cholesteatoma and COM. The results were as follows: 1) The width of the attic was significantly larger in both pars flaccida type and pars tensa type cholesteatoma than in COM. 2) With pars flaccida type cholesteatoma there was a significantly larger distance between the malleus and lateral wall of the attic than with COM. In contrast, the distance between the malleus and medial wall of the attic was significantly larger with pars tensa type cholesteatoma than with COM. 3) With cholesteatoma extending into the antrum, regardless of the type of cholesteatoma, there were significantly larger distances than with COM at the following sites; the width and height of the aditus ad antrum, and the width, height and anterior-posterior diameter of the antrum. However, these distances were not significantly different between cholesteatoma without extension into the antrum and COM. The hitherto demonstrated qualitative impressions of bone destruction in cholesteatoma were quantitatively verified in detail using high resolution computed tomography. PMID- 1619511 TI - [Surgical treatments of adult chronic sinusitis--a study by questionnaire from 434 hospitals in Japan]. AB - Information concerning surgical treatment of adult patients with chronic sinusitis was obtained through questionnaires from 434 hospitals in Japan. The hospitals were authorized for an in-service otorhinolaryngological training institute by the Oto-Rhino-Laryngological Society of Japan. The questionnaires were sent to the hospitals in December, 1989, and answers were obtained from 370 hospitals within 2 months, an 85.3% response rate. The following results were obtained. In 96.2% of the hospitals, permaxillary sinus surgery was performed on patients whose maxillary and ethmoid lesions were severe. With moderate lesions of both the maxillary and ethmoid sinuses, permaxillary sinus surgery and endonasal sinus surgery were performed in 76.0% and 24.9%, respectively. Application of an endoscope for sinus surgery was reported by 89 hospitals. In January, 1990, a further survey was sent to the 89 hospitals where endoscopic sinus surgery was performed. Questionnaire responses were obtained from 75 hospitals. Rigid endoscope was used most frequently and operative microscope was also used. Endoscopy was applied to all of the sinus surgery procedures in 21.6%, and to a portion of the procedures in 74.3% of the hospitals. About 50% of the hospitals performed endoscopic surgery in fewer than 30% of sinus surgery cases. When questioned as whether endoscopic surgery had been successful, 42.6% said yes, 10.7% said no, and 42.6% were unsure. PMID- 1619512 TI - [Quantitative assessment of facial palsy by Moire topography]. AB - It is essential to establish an objective and quantitative method for evaluating facial palsy and to measure the extent of paralysis in order to evaluate therapeutic efficacy, determine prognosis, select appropriate treatment and observe the process of recovery. This study utilized Moire topography, which displays three-dimensional facial symmetry with high precision and is based on light interference theory, to determine the extent of facial palsy in 38 patients (20 men and 18 women) 5 months to 73 years of age. A stereoscopic lattice type Moire camera (FM3013) was connected to a CCD camera and to the monitoring device for confirming Moire stripes. Moire photographs were taken with a thermal imager (FTI-200). The photos were visually and objectively evaluated on the basis of the Moire pattern and were then input into a personal computer with a digitizer for data processing and analysis. To view the functions of facial nerve branches, five Moire photographs were taken: at rest, wrinkling the forehead, closing the eyes lightly, blowing out the cheeks and grinning. Results indicated that the number of stripes and their polarization adequately reflected the function of individual facial nerve branches. Thus, a well-defined Moire pattern could clarify the characteristics of the site and the degree of facial palsy and of recovery from paralysis. It is an analytical method that can be quickly applied and seems especially useful in infants and young children, in whom point-based assessment is difficult. It is possible to quantitatively evaluate facial palsy in terms of the Asymmetry Index (AI), which is 20-25% for severe paralysis, 12 19% for partial paralysis, and 5-10% for an essentially normal condition. However, the numerical value of the AI overlap in all three paralysis categories, indicating that quantitative assessment of paralysis would be difficult. Moire topography is an excellent method of determining the extent of facial palsy, compensating for the short falls of examination-based assessment and permitting reproducible visual, objective, and quantitative evaluation. PMID- 1619513 TI - [The quantitation of Pseudomonas aeruginosa elastase in suppurative chronic otitis media using a sensitive ELISA method]. AB - A sensitive sandwich ELISA method has been developed in order to quantitate the Pseudomonas aeruginosa elastase (PE) of ear discharge from chronic suppurative otitis media (CSOM) patients. Samples were incubated with EDTA-2Na before ELISA in order to inhibit the PE activity which hydrolyzes anti-PE IgG antibody into smaller molecular fragments. Quantitation of PE in middle ear effusions (MEE) from 10 patients with chronic otitis media with effusion (OME) were also performed. In CSOM, 12 of 14 samples revealed a significant amount of PE from 0.6 microliter/ml to 62.1 microliters/ml, which was significantly higher than those in MEE (p less than 0.05). In MEE, 8 of 10 samples were under the detection limit. Two samples in CSOM with Pseudomonas aeruginosa infection had high levels of PE. The quantitation was linear, with a concentration from 5 ng PE/sample to 500 ng PE/sample. This ELISA system is a sensitive method for quantitation of PE requiring only very small samples. PMID- 1619515 TI - [Induction of cytotoxic activity from regional lymph node lymphocytes in head and neck malignant tumor]. AB - Cytotoxic activities of rIL-2-stimulated effector cells from peripheral blood mononuclear cells (PBMC-LAK), and those from the regional lymph node cells (LN LAK) from patients with head and neck malignant tumor were examined by 4-hour 51Cr release assay. Cytotoxicity of LAK cells from involved lymph node (LN (+) LAK) were significantly lower than those of PBMC-LAK. LAK cells from non-involved lymph node (LN (-)-LAK) had a significantly higher cytotoxicity against Daudi cell than PBMC-LAK. Cytotoxic activities against K562 cell and autologous tumor cells mediated by LN (-)-LAK were not significantly different from those by PBMC LAK. However, autologous tumor cell lysis by LN (-)-LAK from lymph nodes showing follicular lymphoid hyperplasia (FLH) pattern was higher than that by PBMC-LAK. The effector cells against autologous tumor cells were characterized CD56+ cells and CD8+ cells (CD8+CD11b- cells) by phenotypic analysis and negative selection assay using immunomagnetic isolation technique. PMID- 1619514 TI - [Study of tinnitus masking by self-recording audiometer]. AB - The tinnitus masking test, in which the minimum masking levels of tinnitus by various pure tones and band noises are measured and used to produce tinnitus masking curves, is one of the methods for evaluating the character of tinnitus. At present, the tinnitus masking test is usually performed using a pure tone audiometer. In this study, tinnitus masking curves were produced using a self recording audiometer (Bekesy audiometer) in 22 cases of tinnitus, and the basic nature of the tinnitus masking curves from the self-recording audiometer was investigated and compared with those from a pure tone audiometer. The results showed no changes in the masking level, and the amplitudes of the tinnitus masking curves from the self-recording audiometer were observed to be at the tinnitus pitches. The amplitude of the tinnitus masking curve showed a negative correlation with tinnitus loudness as measured by the loudness balance test for tinnitus, that is, the amplitude tended to decrease as the tinnitus became louder. This suggests that the loudness of the masking tone influences the tinnitus masking phenomenon. PMID- 1619516 TI - Pyrimidine dimer splitting in covalently linked dimer-arylamine systems. AB - Cyclobutadipyrimidines (pyrimidine dimers) undergo photosplitting which is sensitized by electron donors. We prepared a series of compounds in which a dimer is directly linked to an arylamine, which acts as sensitizer for dimer splitting. Two diastereomers of the dimer-arylamine exhibited very different splitting efficiencies. Also studied were N-methyl, ring methoxy, as well as deuterated derivatives of the sensitizer. These dimer-arylamines had an absorption band with lambda max approximately 300 nm. In each case intramolecular photosensitization of dimer splitting was highly dependent on the solvent, ranging in one instance from phi spl = 0.02 in water to a high value of 0.31 in the least polar solvent mixture examined (1,4-dioxane: isopentane, 1:99). A mechanism is proposed which involves photoinduced electron transfer from arylamine to dimer and splitting of the dimer radical anion. The dependence of splitting on the solvent was rationalized on the basis of retardation of back electron transfer due to Marcus inverted behavior of the charge-separated species. Photolyases might achieve their high efficiency of dimer splitting in part by employing a hydrophobic active site to slow back electron transfer in a similar manner. PMID- 1619517 TI - Preparation of a chemiluminescent imidoester for the non-radioactive labelling of proteins. AB - A chemiluminescent aryl acridinium ester was synthesized which possesses an imidate ester group capable of reacting with proteins under mild conditions. The compound can be detected at levels as low as 5.2 x 10(-19) mol using commercially available luminometers and can therefore be used to produce high specific activity labelled antibodies for use in immunochemiluminometric assays. The imidate ester compares favourably with a previously reported N-succinimidyl ester in terms of its labelling properties but is easier to synthesize, requiring one less step. The compound was used to label affinity purified to synthesize, requiring one less step. The compound was used to label affinity purified sheep antibodies to human parathyroid hormone to demonstrate its utility in a two-site immunochemiluminometric assay for the measurement of intact parathyroid hormone. PMID- 1619518 TI - Combination therapy involving photosensitizing agents. PMID- 1619519 TI - The chick chorioallantoic membrane (CAM) as an in vivo model for photodynamic therapy. PMID- 1619520 TI - Psychoactive drugs and human sexual behavior: the role of serotonergic activity. AB - A wide range of both prescription and nonprescription drugs has been reported to affect human sexual functioning. While the sexual side effects resulting from drug use have often been attributed to adrenergic, anticholinergic or dopaminergic activity, the present review considers the potential role of serotonin. Based on animal studies, serotonin has been shown to either facilitate or inhibit sexual activity depending on which serotonin receptor subtype is activated. However, few studies have been done in the human that assess the effects of drugs that bind selectively to serotonin receptors. Consequently, little is known about the role of serotonin in human sexual functioning. In this review, a wide range of drugs that affect both brain serotonergic systems and human sexual behavior is examined in an effort to determine the possible role of serotonin in human sexual behavior. A review of the literature is consistent with the hypothesis that the 5-HT1A and the 5-HT2 receptor subtypes play a facilitatory role in human sexual behavior. The evidence suggests that drugs that act as agonists on these receptor sites enhance sexual functioning in the human, while those that act as antagonists inhibit sexual functioning. PMID- 1619521 TI - Reaching the unreached: targeting hidden IDU populations with clean needles via known user groups. AB - Needle exchange is a practical and important part of the Dutch prevention strategy to check the spread of HIV among injecting drug users (IDUs). However, needle-exchange programs are often tied to drug treatment programs that only reach a limited number of IDUs. To overcome this limitation, alternative designs are considered and initiated. This article describes a community-based approach to needle exchange that is built on empowerment of, and intense participation by, known IDUs to target unknown IDUs for delivery of clean needles. The needle exchange patterns of the IDUs participating in this collective scheme are compared to those of other users who exchanged needles on an individual basis. It was found that this approach extended the reach of the program to a great degree and that it was well received in the IDU community. However, the results were negatively influenced by police activities aimed at closing down places where drugs were used and sold. It is concluded that engaging IDUs in peer-group directed prevention efforts is both feasible and promising. PMID- 1619522 TI - Marathon therapy: treating rape survivors in a therapeutic community. AB - Odyssey House is a therapeutic community (TC) in New York City that treats a wide range of drug abusers. For over 20 years. Odyssey House has conducted an annual marathon therapy group for women who are rape survivors. This article summarizes the program's experience with the marathon and reports on its therapeutic accomplishments. PMID- 1619523 TI - A heroin revival in Miami: notes from a street survey. PMID- 1619524 TI - Retrospective reports of psychiatric symptoms before, during, and after drug use in a recovering population. PMID- 1619525 TI - Staying off methadone maintenance. PMID- 1619526 TI - Twenty-four-hour esophageal pH monitoring: what's the score? PMID- 1619528 TI - Evaluation of reflux episodes during simultaneous esophageal pH monitoring and gastroesophageal reflux scintigraphy in children. AB - Gastroesophageal pH monitoring and reflux scintigraphy were simultaneously performed in 65 children, who were being investigated for suspected gastroesophageal reflux disease. The aim of the study was to compare, peak per peak, the information provided by the two techniques during a 1-h simultaneous recording period. During this period, 123 reflux episodes were recorded with both techniques, but only six occurred simultaneously. Significantly more reflux episodes were recorded on scintigraphy (n = 88; p less than 0.05), particularly during the first half-hour period (n = 62), if compared with the number of pH drops greater than 1 unit, even at pH levels higher than 4 (n = 41; p less than 0.05). It is concluded that the two techniques explore differently the reflux phenomenon. PMID- 1619527 TI - Comparison of methods of assessing 24-hour intraesophageal pH recordings in children. AB - Prolonged intraesophageal pH recording, an important test in the evaluation of children with suspected gastroesophageal reflux (GER) disease, may be performed and evaluated by markedly different methodologies. Twenty-four-hour intraesophageal pH recordings from 67 consecutive infants were evaluated by three scoring methods: early postprandial, late postprandial, and total recording. In addition, the scoring methods were evaluated for their ability to identify 20 infants with clinically defined GER-induced acute life-threatening events (ALTEs). There were significant positive correlations between each pair of scoring systems (early postprandial with late postprandial, early postprandial with total recording, and late postprandial with total recording). However, our data indicate that the three methods identify different groups of patients. The early and late postprandial methods disagreed in designating "normal" versus "abnormal" in approximately 20% of patients. The total recording method was more likely to label patients as normal than either of the other methods; it yielded normal results in approximately one half of patients abnormal by either the early or the late postprandial methods. Patients with GER-induced ALTEs were identified by the early postprandial method in 90% of cases, the late postprandial method in 95% of cases, and the total recording method in only 45% of cases. By applying three different scoring methods to the same 24-h intraesophageal pH recording, we demonstrated less-than-perfect correlation among the methods. Long-term follow-up is needed to determine if these differences are of clinical significance. We feel that effort should be directed toward standardizing the approach to intraesophageal pH monitoring in infants. PMID- 1619529 TI - Bacterial ileocecitis caused by Escherichia coli O157:H7. AB - Escherichia coli O157:H7 is most commonly linked to hemorrhagic colitis and the hemolytic uremic syndrome. Diagnostic ultrasound was used to demonstrate terminal ileum abnormalities suggestive of bacterial ileocecitis, a recently described entity that resembles acute appendicitis, in a patient whose stool culture yielded E. coli O157:H7. This case extends the spectrum of disease caused by E. coli O157:H7 and expands the number of organisms that can cause bacterial ileocecitis. PMID- 1619530 TI - In vivo effect of yogurt on excretion of enteropathogen Escherichia coli RDEC-1 during acute diarrhea in the just-weaned rabbit. AB - Yogurt has been shown to inhibit, by various mechanisms, pathogenic bacterial growth in vitro, including that of the rabbit Escherichia coli strain RDEC-1. To determine whether this in vitro inhibition by yogurt has an in vivo counterpart, 60 newly weaned New Zealand rabbits were randomly assigned to receive a diet supplemented with either milk or yogurt. Four days later, rabbits were infected intragastrically with 10(8) E. coli strain RDEC-1. During the 30 days postinfection, animals were checked regularly for weight, stool characteristics, and fecal excretion of bacteria. Results show that the duration of diarrhea as well as bacterial excretion were the same in the milk and yogurt groups, indicating that in vivo, yogurt did not interfere with the growth of the pathogenic E. coli strain RDEC-1. The pattern of the survival curves was significantly different in the two groups (p less than 0.03), but the difference between their mortality at 30 days postinfection was not significant (80% in the milk group versus 67% in the yogurt group). These results indicate that the bactericidal activity of yogurt observed in vitro against the E. coli strain RDEC 1 does not have an in vivo counterpart in the model of the just-weaned rabbit infected by RDEC-1. PMID- 1619532 TI - Breath methane excretion in Hong Kong Chinese children. AB - The factors which determine whether an individual is a methane excretor or a nonexcretor are not clearly understood. Genetic makeup, ethnic origin, diet, environment, or an interaction of all these factors have been implicated. In order to delineate the incidence, the age of onset, and environmental factors that may influence the excretion of methane in our community, we investigated a total of 425 Chinese children in Hong Kong (204 females, 221 males). End expiratory breath samples were collected after an overnight fast and measured by gas-chromatography using a flame ionization detector. Thirty one children (7.3%) excreted at least 1 ppm methane above the ambient level (median = 6.4, range = 1.8-26.0 ppm). There was no difference in methane excretion status and pattern between the sexes or between children who lived at home and those who lived at an institution. There was a general increase in the number of methane excretors with age, but a statistically significant increase was reached only after 14 years of age. The amount of methane excreted was unrelated to age and there were no excretors detected under the age of 5 years. It is concluded that the methane excretion pattern of these children was generally similar to those previously reported from other regions, but the incidence is much lower and the age of onset appears to be more gradual. PMID- 1619531 TI - Reference values of the steatocrit and its modifications in diarrheal diseases. AB - Conflicting results have been reported on the use of the steatocrit to measure fecal fat excretion. Aiming to assess the reliability of this method and its usefulness in the diagnosis of intestinal enteropathies, we measured the steatocrit in 747 healthy children and 442 children with diarrhea grouped according to diagnosis. The steatocrit was found to correlate strictly (r = 0.93) with the chemical measurement of fecal fat. Reference values and ranges were established. The maximal steatocrit was observed in neonates; afterwards, it progressively decreased to an undetectable level in children older than 2 years of age. A steatocrit abnormally high for age was found in 20% of patients with acute diarrhea and in 53% of those with chronic diarrhea. All celiac patients with a gluten-containing diet showed a marked increase of steatocrit. We conclude that the steatocrit is a reliable and easy-to-perform test, which quickly provides valuable information in the diagnostic workup of the child with diarrhea. PMID- 1619533 TI - Plasma and gastric juice levels of prostaglandins in critically ill children. AB - The levels of prostaglandin (PG) E2 and 6-keto-PGF1 alpha (stable metabolite of prostacyclin) in plasma and gastric juice were determined in 113 critically ill children and adolescent, and compared to those registered in a plasma control group of 24 children and a gastric juice control group of 15. The gastric juice concentration of PGE2 is our patients [9.2 +/- 3.1 (SEM) pg/ml] was significantly lower (p = 0.001) than in the control group [81.1 +/- 18.1 (SEM) pg/ml]. There were no differences in plasma levels of PGE2 and plasma gastric juice levels of 6 keto-PGF1 alpha between the patients and the control groups. Children who died had lower plasma levels of PGE2 [6.2 +/- 2.2 (SEM) pg/ml] and gastric juice levels of PGE2 [2.3 +/- 0.8 (SEM) pg/ml] than the survivors (p less than 0.05). The gastric juice concentration of PGE2 was also lower in children who suffered important upper gastrointestinal bleeding, although the difference did not reach statistical significance. PMID- 1619534 TI - Determination of body composition in growing rats by total body electrical conductivity. AB - Total body electrical conductivity (TOBEC), measured with an Em-Scan SA-1 analyzer, was evaluated as a means of estimating fat-free mass and total body water content noninvasively in small laboratory animals. Ninety-four rats whose weight ranged from 5.53 to 170.84 g at 0-50 days of age were studied. The animals were killed by intraperitoneal injection of a pentobarbital overdose. After weight, crown-rump length (CRL) and TOBEC were measured, and the animals were minced with scissors and desiccated to constant weight in a convection oven. Fat was extracted by multiple bathings in petroleum ether followed by Soxhlet extraction. Fifty-four rats were used to determine the relation between fat-free mass (FFM), total body water (TBW), and TOBEC# (E) by regression analysis. The best correlations were observed between FFM and (E x CRL)1/2 (r = 0.995, p less than 0.0001). Forty rats were used to determine the predictive value of TOBEC estimates. With this instrument, TOBEC tended to underestimate FFM by an average of 3.9% and TBW by 5.3%. Accuracy was questionable for animals smaller than 13 g and TOBEC did not provide useful estimates of total body fat. Subject to these limitations, TOBEC instruments should prove to be useful for sequential in vivo estimations of body composition during growth and development of small animals. PMID- 1619535 TI - Changes in fatty acid profiles of red blood cell membranes mediated by dietary nucleotides in weanling rats. AB - Dietary nucleotides have been described to play multiple physiological roles. We examined the effect of feeding, for 4 weeks, nucleotide-supplemented diets (N-50 and N-250) on red blood cell (RBC) membrane fatty acid composition in weanling rats. Long-chain polyunsaturated fatty acids (LC-PUFA) of the n-6 series, especially arachidonic acid, increased in total RBC phospholipids in N-50 and N 250 groups. Concentrations of LC-PUFA of the n-3 series were preserved or slightly decreased. Saturates and monoenates also decreased. Phosphatidylethanolamine and sphingomyelin followed the variations observed for total phospholipids. Phosphatidylcholine showed a different response; saturated fatty acids increased while n-6 LC-PUFA decreased. Dietary nucleotides seem to affect the conversion of essential fatty acids to their long-chain derivatives in weanling rats in a similar way to that occurring in newborn infants during early life. These results show that the rat may be a valid model with which to study the biochemical mechanisms by which dietary nucleotides affect fatty acid desaturation. PMID- 1619536 TI - Multiple biliary papillomatosis in a child. PMID- 1619537 TI - Veno-occlusive disease of the liver after combined adjuvant chemotherapy for a 1 year-old boy with rhabdomyosarcoma: potential usefulness of the gabexate mesylate (FOY). AB - A tumor in the left thigh of a 1-year-old boy was diagnosed as rhabdomyosarcoma (stage 1). The tumor was excised and vincristine (1.5 mg/m2 given twice), actinomycin D (15 micrograms/kg given five times), and cyclophosphamide (600 mg/m2 given once) were prescribed. On the 12th day after initiating this chemotherapy, his liver rapidly enlarged and ascites, pleural effusion, and disturbance of consciousness due to hepatic failure successively appeared. Before these clinical signs appeared, laboratory data demonstrated enhanced coagulation and fibrinolysis such as thrombocytopenia refractory to platelet transfusion and a marked increase in fibrinogen and fibrin degradation product (FDP). Hepatic veno-occlusive disease (VOD) was suspected, and based on the laboratory data indicating enhanced coagulation, anticoagulant (gabexate mesylate; FOY), diuretic, and supportive therapy for hepatic failure was begun. The clinical course was favorable and recovery was complete in 2 months, with no sequelae. We propose that platelet count, coagulation factor levels, and FDP may be useful for the early detection of VOD, and an anticoagulant drug such as FOY is worthy of consideration for the prevention and treatment of VOD. PMID- 1619538 TI - Effects of indomethacin in congenital chloride diarrhea. AB - Clinical and biochemical effects of indomethacin were monitored in a patient with congenital chloride diarrhea (CCD) before and after 10 days of therapy. During indomethacin treatment, no clinical improvement could be achieved whereas hyperreninemia and hyperaldosteronism improved. Excretion rates of prostaglandin (PG) E2, PGF2 alpha, as well as PGE-M were found to be slightly raised and decreased during therapy with indomethacin. However, loss of electrolytes remained substantially unchanged. Prostaglandins, therefore, seem to play no important role in intestinal loss of electrolytes in CCD, and it is suggested that indomethacin is of no importance in the treatment of patients with CCD. PMID- 1619540 TI - Somatic gene therapy in gastroenterology: approaches and applications. AB - Somatic gene therapy represents a new approach for treating a variety of genetic and acquired diseases and has many potential applications in gastroenterology. Somatic gene therapy is based on the ability to transfer recombinant genes efficiently into somatic tissues, such as the liver or intestine, and achieve expression of the recombinant gene product. Gene transfer could be used to replace genetically defective gene functions or prevent the progression of acquired or multifactorial diseases. The therapeutic application of gene transfer technologies requires development of methods for achieving efficient transfer and expression of recombinant gene products, research directed at developing strategies for altering the course of disease, and clinical research aimed at assessing both the technical feasibility and therapeutic efficacy of this approach. PMID- 1619539 TI - Hypertrophic gastropathy with transient sessile polyps. AB - We report an 8-year-old boy with hypertrophic gastropathy (HG) associated with duodenal Giardia lamblia infestation. The follow-up was complicated by the development of gastric polyps at the site of previous biopsies that spontaneously disappeared within 15 months. Despite the histological similarity, the different course between Menetrier's disease (MD) in adults (chronic, with frequent development of sessile or pedunculate polyps) and HG (uncomplicated and usually spontaneously resolving) suggests a different pathogenesis. Viral (cytomegalovirus) and bacterial (Helicobacter pylori) infections have been described in association with HG and they could play an important pathogenetic role. The term HG better defines the childhood disease in which a conservative management is recommended. PMID- 1619541 TI - Helicobacter, Helicobacter everywhere, and not a drop to drink! PMID- 1619542 TI - Erythromycin--additional perspective on its prokinetic effects. PMID- 1619543 TI - Penicillamine hepatotoxicity in the treatment of Wilson's disease. PMID- 1619544 TI - Protein-losing enteropathy and Helicobacter pylori. PMID- 1619545 TI - Necrotizing enteritis involving the second part of the duodenum. PMID- 1619547 TI - Sensation seeking, stress, and adolescent injuries: a test of stress-buffering, risk-taking, and coping skills hypotheses. AB - The potential stress-buffering effects of sensation seeking were assessed in a prospective study involving high school athletes. A significant positive relation between major negative sport-specific life events and subsequent injury time-loss occurred only for athletes low in sensation seeking. No evidence was obtained for a competing hypothesis that high sensation seeking would constitute an injury vulnerability factor by increasing risk-taking behaviors. Although low sensation seekers reported poorer stress management coping skills, there was no evidence that differences in coping efficacy mediated the injury vulnerability difference. Results indicate that sensation seeking is a stress-resiliency factor and suggest the utility of assessing relations between life stressors and outcomes that occur within the same environmental context. PMID- 1619546 TI - Intestinal disaccharidase activity in giardiasis. PMID- 1619548 TI - Compartmentalization of positive and negative self-knowledge: keeping bad apples out of the bunch. AB - Three studies examined whether categorical organization of knowledge about the self explains variance in self-esteem and depression beyond that which is accounted for by sheer amount of positive or negative content. Compartmentalization is the tendency to organize positive and negative knowledge about the self into separate, uniformly valenced categories (self-aspects). As long as positive self-aspects are activated, access to negative information should be minimized. Compartmentalization was associated with high self-esteem and low depression scores for individuals whose positive self-aspects were important; when negative self-aspects were important, compartmentalization was correlated with low self-esteem and high depression scores. An analysis of self aspect labels showed that individuals with compartmentalized organization define negative self-aspects in especially narrow terms. A possible relationship between compartmentalized organization and cognitive complexity is discussed. PMID- 1619549 TI - The generality of the automatic attitude activation effect. AB - Fazio, Sanbonmatsu, Powell, and Kardes (1986) demonstrated that Ss were able to evaluate adjectives more quickly when these adjectives were immediately preceded (primed) by attitude objects of similar valence, compared with when these adjectives were primed by attitude objects of opposite valence. Moreover, this effect obtained primarily for attitude objects toward which Ss were presumed to hold highly accessible attitudes, as indexed by evaluation latency. The present research explored the generality of these findings across attitude objects and across procedural variations. The results of 3 experiments indicated that the automatic activation effect is a pervasive and relatively unconditional phenomenon. It appears that most evaluations stored in memory, for social and nonsocial objects alike, become active automatically on the mere presence or mention of the object in the environment. PMID- 1619550 TI - Changes in the marital relationship after the first baby is born: predicting the impact of expectancy disconfirmation. AB - A longitudinal study of 50 couples during the transition to first parenthood examined how failure to confirm expectations regarding the sharing of child-care and housekeeping responsibilities influenced postpartum reports of marital satisfaction. On the basis of recent theories of expectancy confirmation processes, 5 variables representing strength and importance were identified as possible moderators. As predicted, disconfirmation of stronger and more important expectations generally led to more negative reports about the marriage. Surprisingly, some subsets of wives showed opposite reactions; less negative feelings when they were doing more than they expected. These findings were interpreted in terms of personal and role traditionality influencing the valence of the reactions to expectancy disconfirmation. PMID- 1619551 TI - Emotion and autonomic nervous system activity in the Minangkabau of west Sumatra. AB - Physiology and emotional experience were studied in the Minangkabau of West Sumatra, a matrilineal, Moslem, agrarian culture with strong proscriptions against public displays of negative emotion. Forty-six Minangkabau men were instructed to contract facial muscles into prototypical configurations of 5 emotions. In comparison with a group of 62 Ss from the United States, cross cultural consistencies were found in (a) autonomic nervous system (ANS) differences between emotions and (b) high configuration quality being associated with increased ANS differentiation and increased report of emotional experience. These findings provide the first evidence that these patterns of emotion-specific ANS activity and the capacity of voluntary facial action to generate this activity are not unique to American culture. PMID- 1619552 TI - Trust, distrust, and interpersonal problems: a circumplex analysis. PMID- 1619553 TI - The revealing of Mr. Stubbs: stories from the heart. PMID- 1619554 TI - Grow days: nurturing spiritually healthy teens. PMID- 1619555 TI - Toning the temple: a church-based health fair. PMID- 1619556 TI - Realities: a summer in Zambia. PMID- 1619557 TI - To smile again. PMID- 1619558 TI - Reminiscence: a Biblical basis for telling our stories. PMID- 1619559 TI - Lamentations. PMID- 1619560 TI - Drug delivery via the mucous membranes of the oral cavity. AB - The delivery of drugs via the mucous membranes lining the oral cavity (i.e., sublingual and buccal), with consideration of both systemic delivery and local therapy, is reviewed in this paper. The structure and composition of the mucosae at different sites in the oral cavity, factors affecting mucosal permeability, penetration enhancement, selection of appropriate experimental systems for studying mucosal permeability, and formulation factors relevant to the design of systems for oral mucosal delivery are discussed. Sublingual delivery gives rapid absorption and good bioavailability for some small permeants, although this site is not well suited to sustained-delivery systems. The buccal mucosa, by comparison, is considerably less permeable, but is probably better suited to the development of sustained-delivery systems. For these reasons, the buccal mucosa may have potential for delivering some of the growing number of peptide drugs, particularly those of low molecular weight, high potency, and/or long biological half-life. Development of safe and effective penetration enhancers will further expand the utility of this route. Local delivery is a relatively poorly studied area; in general, it is governed by many of the same considerations that apply to systemic delivery. PMID- 1619561 TI - Relationship between in vivo skin blanching and in vitro release rate for betamethasone valerate creams. AB - Betamethasone valerate creams from two firms were evaluated using the skin blanching procedure. In both studies, the same cream formulation exhibited significantly higher blanching compared to the other product. An in vitro release rate was determined for these betamethasone valerate cream products using a diffusion cell system, with a cellulose acetate membrane and a 60% ethanol:water receptor medium. The release rate (flux) of betamethasone valerate was higher for the higher blanching formulation and was statistically different from the other product. The integrity of the cellulose acetate membrane in 60% ethanol:water mixture was ascertained using hydrocortisone cream product. The in vitro drug release method, using a diffusion cell system and a synthetic membrane, can serve as a good quality control test method for topical creams. PMID- 1619562 TI - Two steady-state pharmacokinetic parameters: peak-to-trough drug concentration ratio and time of occurrence of time-averaged concentration. PMID- 1619563 TI - Zidovudine serum, cerebrospinal fluid, and brain concentrations following chronic administration of a new zidovudine formulation via an implantable pump in dogs [corrected]. AB - Zidovudine (AZT), prepared as an alkaline solution, was administered iv and intraarterially (ia) by continuous infusion via an implantable pump in dogs. The AZT serum and cerebrospinal fluid (CSF) concentrations were measured over a 28 day treatment period by HPLC. Terminal brain AZT concentrations were also measured. Control (vehicle only) animals were also studied. All animals were evaluated for pathological changes associated with the AZT and vehicle infusions in catheterized vessels and other organs. In the iv AZT treatment group, serum AZT concentrations were relatively constant, with individual coefficients of variations (%CV) of 20% or less. Mean CSF:serum and brain:serum AZT concentration ratios were 0.149 and 0.212, respectively. In the ia AZT treatment group, serum AZT concentrations were more variable than in the iv group, with %CV ranging from 22 to 79%. The fluctuations in serum concentrations were attributed to temporary blockages of the outflow catheter. Mean CSF:serum and brain:serum AZT concentration ratios were 0.126 and 0.249, respectively. Pathological changes, similar in both control and treatment groups, included endothelial denudation and myointimal proliferation at the infusion sites. The conclusions of the study are (1) steady-state greater than 1 microM AZT serum concentrations can be maintained chronically by use of an implantable pump containing a basic pH AZT solution; (2) ia delivery of AZT did not increase central nervous system uptake compared with iv administration; and (3) morbidity associated with the infused solutions does not seem to be a limitation for this mode of therapy. PMID- 1619564 TI - Fraction of the bioavailable dose remaining in the body at the time of peak plasma concentration in a linear, open, one-compartment model. PMID- 1619565 TI - Influence of D-glucose-induced water absorption on rat jejunal uptake of two passively absorbed drugs. AB - The intestinal absorption of D-glucose is coupled to transepithelial sodium transport and this process generates intestinal water absorption. In situ jejunal perfusions were performed in rats to determine the extent of water transport as a function of perfusion flow rate, perfusate osmolality, and D-glucose concentration. Jejunal perfusions of iso-osmolar D-glucose, at flow rates and concentrations representative of the fed state, increased the dimensionless membrane permeabilities of the analgesic acetaminophen from 0.6 to 1.4, and that of the corticosteroid prednisolone from 1.6 to 2.2. This increase is less important for the more hydrophobic prednisolone since its baseline permeability (1.6) is indicative of complete uptake from solution, while the lower baseline permeability (0.6) of the more hydrophilic acetaminophen represents incomplete membrane uptake. The results suggest that nutrient-induced water transport can enhance jejunal uptake of small hydrophilic solutes. This phenomenon may contribute to variability in the absorption of drugs in this physicochemical class during the fed state. PMID- 1619566 TI - Absolute bioavailability, rate of absorption, and dose proportionality of sulpiride in humans. AB - The pharmacokinetics of orally administered sulpiride was determined in a series of three studies. In the first study, 12 subjects received an oral solution (200 mg) and an iv dose (100 mg). The second study also included an iv dose, and examined the absorption of 200-, 300-, and 400-mg doses given as 50-mg capsules to six subjects. The third study compared the bioavailability of a 200-mg capsule dose with a 200-mg im dose in eight subjects. The concentration of sulpiride in plasma, red blood cells, and urine was measured by HPLC. The disposition of the drug was generally best described by a two-compartment pharmacokinetic model, with absorption appearing to occur by two sequential zero-order processes. The fraction of dose absorbed after oral administration was approximately 30% based on plasma and urine data. After the 200-mg dose, the mean elimination half-life was 7.0 h, and the mean residence time was 8.4 h. For each subject, total clearance, corrected for the fraction absorbed, and renal clearance were similar. The dose proportionality study demonstrated linear disposition kinetics. PMID- 1619567 TI - Modulation of the effector functions of cytolytic T-lymphocytes with synthetic peptide inhibitors of protein kinases. AB - The hypothesis was tested that it is possible to influence cellular responses of intact cells using synthetic peptide substrates, pseudosubstrates, and inhibitors of protein kinases. Using cytotoxic T-cells (CTL), we demonstrate here that some basic amino acid-containing synthetic peptide substrates of protein kinases [e.g., of cGMP-dependent protein kinase (peptide PKG-S), synthetic peptide inhibitor of cGMP-dependent protein kinase (peptide PKG-I), and peptide corresponding to the tyrosine phosphorylation site in pp60src (peptide RR-src)] were strongly inhibitory in T-cell receptor (TCR) and T-cell growth factor, interleukin 2 (IL-2)-triggered proliferation of CTL. These peptides also inhibited other cellular responses of CTL. Peptides which contain basic amino acids, but do not have substrate specificity determinants for protein kinase, were not inhibitory. The inhibition with peptides is not due to their toxicity, since no cell death was observed by the trypan blue exclusion test and by lactate dehydrogenase release. Use of the granule exocytosis assay provided opportunities to clarify the mechanism of the peptide action. Tested peptides inhibited not only cell-surface ligand-induced CTL activation, but also affected cell-surface receptor-independent CTL activation (granule exocytosis and gamma-interferon secretion) induced by the synergistic action of the protein kinase C activator (PMA) and ionophore A23187. It was found that minor changes in amino acid composition or amino acid position in the synthetic peptides dramatically change their ability to affect lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619568 TI - Possible effect of pigment on the pharmacokinetics of ofloxacin and its excretion in hair. AB - The mechanism of excretion of the antimicrobial ofloxacin in human scalp hair was investigated. When black and white hairs were taken from a patient with grizzled hair, who had been treated with ofloxacin, a much larger quantity of the drug was detected in the black hair. To study this difference and to elucidate the cause, ofloxacin (6, 20, and 60 mg/kg/day, b.i.d.) was administered ip for 5 weeks to albino and pigmented rats, whose backs had been depilated beforehand. In the last week of administration, the time-plasma concentration profile of ofloxacin was determined. One week after the last dosing, the newly grown hair on the depilated area was collected, and the drug concentration in hair was measured. The concentration in hair of the pigmented rats correlated significantly with the daily dose, area under the plasma concentration curve (AUC), and maximum plasma concentration (Cmax) at steady state, whereas that in the albino rats correlated with the dose and Cmax only, because AUC did not increase linearly with the dose in the albino rats. Moreover, the drug concentration in the hair of the pigmented rats was always much larger than that in the hair of the albino ones, although AUC and Cmax did not differ greatly between both rat groups. The findings suggest that ofloxacin is excreted in the hair in relation to the dose administered, and that the mechanism of the excretion is closely linked with the presence of melanin. PMID- 1619569 TI - Discontinuous alterations of platelet structure and function by bound, ionizable verapamil. AB - We have investigated several effects of verapamil (5-[(3,4 dimethoxyphenethyl)methylamino]-2-(3,4-dimethoxyphenyl)-2- isopropylvaleronitrile) on platelet structure and function. At concentrations below a threshold of approximately 4.2 x 10(7) molecules.cell-1, verapamil binds to platelets according to a typical Langmuir adsorption isotherm (i.e., binding is saturable and noncooperative). By extrapolation, we calculate that saturation would occur at 6.8 x 10(7) +/- 1.9 x 10(7) molecules.platelet-1, with one bound verapamil molecule per two membrane phospholipids. Saturation is never achieved, however, because past the threshold surface concentration, the adsorption isotherm becomes discontinuous and further adsorption becomes a linear function of the concentration of drug in solution. We attribute this discontinuity to disorganization of the membrane bilayer which is stretched beyond cohesion by insertion of too many amphiphilic molecules of a length shorter than that of the phospholipid. The partitioning of verapamil between the bulk aqueous phase and the newly created lipid phase would then account for the linear portion of the adsorption isotherm. The discontinuity of binding is accompanied by discontinuities in the verapamil-dependent swelling of platelets and the verapamil-dependent inhibition of both ADP-inducible binding of fibrinogen to, and aggregation of, platelets. In contrast, N-methylverapamil (5-[(3,4 dimethoxyphenyl)- methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile), a hydrophilic quaternary amine derivative of verapamil, neither swells platelets nor inhibits the ADP-dependent processes that we investigated. From this we conclude that deprotonated verapamil is the operative species of the drug. Collectively, these data suggest that verapamil alters platelet structure and function by mechanisms involving disorganization of the platelet plasma membrane. PMID- 1619570 TI - Use of fractal geometry to determine effects of surface morphology on drug dissolution. AB - We extend and modify the Noyes-Whitney equation and the Hixon-Crowell cube root law to include surface roughness effects on the dissolution rate of drugs. The problem is treated theoretically in terms of the fractal reaction dimension, DR, of the effective surface which undergoes dissolution. Effects of changes in DR on the dissolution rate are identified and explained. PMID- 1619572 TI - Polymeric sorbents for bile acids. I: Comparison between cholestyramine and colestipol. AB - Isotherms for the sorption of bile acids at 20 degrees C, in tris(hydroxymethyl)aminomethane.HCl(tris) and KH2PO4-NaOH (phosphate) buffers (pH 7.4), indicate that the binding by cholestyramine and colestipol is mainly through ionic linkages, although hydrophobic interactions are also of importance. Cholestyramine has a higher sorption capacity for bile acids, in both buffers, than colestipol. The chloride form of cholestyramine has a higher capacity for cholate in tris buffer than the iodide form. Increased ionic strength of the medium leads to decreased amounts of sorption. PMID- 1619571 TI - Mechanism of skin penetration-enhancing effect by laurocapram. AB - In order to clarify the mechanism of action of laurocapram (Azone) on the skin permeation of drugs, the following experiments were done. First, the effect of Azone on the skin components was compared with that of other penetration enhancers. Azone markedly fluidized liposomal lipids (as a model lipid system) compared with other enhancers. Ethanol extracted large amounts of the stratum corneum lipids, whereas Azone did not. These results suggest that the effect of Azone on the lipids in the stratum corneum is not the same as that of ethanol. In addition, ethanol increased the amount of free sulfhydryl (SH) group of keratin in the stratum corneum, whereas Azone did not directly affect the stratum corneum protein. Azone increased water content in the stratum corneum, as measured by skin conductance. This effect might be a reason for the action of Azone. For further understanding, the enhancing effects of Azone on the skin permeation of several model compounds (alcohols, sugars, and inorganic ions) were compared with the effects of pretreatment with distilled water, which was thought to increase water-holding capacity, and pretreatment with ethanol, which was thought to affect the lipids and protein in the skin barrier (i.e., stratum corneum). Pretreatment with water or ethanol enhanced skin permeation of hydrophilic compounds, whereas they decreased that of octanol, a hydrophobic compound. The tendency of Azone to increase or decrease the skin permeation rate of most compounds was similar to that of pretreatment with water or ethanol. However, the effect of Azone on the skin permeation of inorganic ions was relatively low, whereas that of pretreatment with water or ethanol was high.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619573 TI - Role of sulfhydryl-containing agents in the healing of erosive gastritis and chronic gastric ulceration in the rat. AB - One milliliter of 1, 2, or 5% DL-cysteine (cysteine) or DL-methionine methylsulfonium chloride (MMSC) was instilled into the rat stomach 1, 24, and 48 h after giving ethanol (1 mL of 40% solution) by gavage. One hour following the administration of ethanol, gastric mucosal injury was seen in all the animals (22.6 +/- 1.1 mm2, mean +/- SEM; n = 10). Twenty-four hours after giving the ethanol, all the rats treated with cysteine or MMSC still had the mucosal injury. Treatment with 2% cysteine or MMSC significantly (p less than 0.01) reduced the extent of this injury (10.2 +/- 0.6 and 10.1 +/- 0.5 mm2, respectively, versus 20.7 +/- 1.2 mm2, mean +/- SEM; n = 10), an action that was similarly achieved by the 5% solutions (10.1 +/- 0.5 and 9.9 +/- 0.3 mm2, respectively, versus 20.7 +/- 1.2 mm2, mean +/- SEM; n = 10). Forty-eight hours following the administration of ethanol, 30% of the animals given 1% cysteine or MMSC still had gastric mucosal injury, which was significantly (p less than 0.001) less extensive than that seen with ethanol alone (3.8 +/- 0.3 and 4.1 +/- 0.3 mm2, respectively, versus 13.1 +/ 0.8 mm2, mean +/- SEM; n = 10). At this time period, however, none of the animals treated with 2 or 5% solutions of cysteine or MMSC still had any injury. Healing of the ethanol-induced injury was confirmed microscopically and was achieved by regeneration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619574 TI - Phenylbutazone action on dimiristoyl phosphatidylcholine liposome phase transition and 8-anilino-1-naphthalene sulfonate binding. AB - Phenylbutazone (PhB), a powerful anti-inflammatory drug, is able to modify the phase transition of phospholipid bilayers without changing its calorimetric enthalpy (delta Hcal), as can be shown by differential scanning calorimetry (DSC) experiments. Under PhB interaction, dimiristoyl phosphatidylcholine (DMPC) multilamellar liposomes (MLV) undergo lateral phase separation as a result of immiscibility in the bilayer plane. On the other hand, the binding of the anionic fluorescent probe 8-anilino-1-naphthalene sulfonate (ANS) to the surface of DMPC liposomes is altered by PhB. Even though the quantum efficacy of the probe fluorescence emission remains unaffected, the negative cooperativity of the binding process disappears, with the intrinsic dissociation constant showing only a minor variation. From these results it is concluded that PhB would be most likely located close to the lipid:water interface. PMID- 1619575 TI - Mechanism of diffusion of monosubstituted benzoic acids through ethylene-vinyl acetate copolymers. AB - Ethylene-vinyl acetate (EVAc), a biocompatible copolymer, has been employed as the rate-controlling membrane in several drug delivery systems. To study the mechanism(s) of diffusion of drugs through EVAc membranes, the diffusion, permeability, and partition coefficients of monosubstituted benzoic acids were studied as a function of vinyl acetate content. The diffusion coefficients were found to occupy a narrow range, but the permeability and partition coefficients were found to increase in a nonlinear fashion as a function of vinyl acetate content, indicating that the diffusion process was partition governed. The partitioning data were analyzed on the basis of the partitioning between the vinyl acetate moiety and the aqueous phase, assuming the formation of 1:1 benzoic acid:vinyl acetate complexes. The effects of ionization and the addition of 2 propanol to the diffusion medium were studied. The results suggest that the un ionized neutral forms of the benzoic acids are responsible for transport across the copolymer. Altering the composition of the medium by addition of 2-propanol increased the donor phase solubility of the acid, the steady-state rate, and the permeability, suggesting that cosolvent modification provides an excellent chemical means to increase release rates. PMID- 1619576 TI - Examination of self-crosslinked gelatin as a hydrogel for controlled release. AB - A gelatin matrix crosslinked by extensive dehydration was examined for use in controlled drug delivery in this preliminary investigation. Crosslinking is necessary to prevent gelatin dissolution and immediate drug release at body temperature. Treatment at 105 degrees C and reduced pressure induced crosslinking in discs prepared from Type B gelatin. Crosslinking was evaluated by determining changes in gelatin solubility at 37 degrees C in a USP paddle dissolution apparatus. The crosslinking treatment was reproducible and resulted in 90% of the original gelatin mass remaining after 12 h in water and in phosphate buffer solutions of pH 3 and 6.4. The treated gelatin discs remained intact for greater than 24 h at pH 6.4. Chlorpromazine.HCl (CPZ) was incorporated as a model drug by soaking the treated gelatin discs in an aqueous solution of the drug. Release of CPZ at 37 degrees C in the dissolution apparatus was fitted to an empirical equation. A coefficient of this equation was used as the initial release rate for comparison between different release profiles. The roles of drug solubility, matrix swelling and erosion, and potential drug-matrix interactions were examined by conducting release studies at pH values of 3, 4, 6.4, and 7.4. The insoluble, un-ionized form of the drug had the slowest release rate. The soluble, ionized form under conditions of maximum swelling and a possible drug-matrix repulsive interaction had the fastest release rate. General electrostatic drug-matrix interactions were noted which could influence the drug release rate depending on conditions of the study. The times for 50% release of CPZ ranged from 1.8 to 11.3 h. PMID- 1619577 TI - Determination of fenoverine, a modulator of smooth muscle motility, in capsules and in human plasma: application to dosage form stability and a pilot study in humans. AB - Fenoverine is a novel, potent, musculotropic, spasmolytic agent that affects primarily the gastrointestinal tract, bile duct, and female genital organs. A simple, specific, and accurate HPLC method was developed for the determination of fenoverine in capsules and plasma. This method has been successfully applied to stability studies of fenoverine capsules and to a pilot study in a normal, healthy volunteer following oral administration of fenoverine. For the determination of fenoverine in capsules, a Nucleosil 5-micron CN column, with acetonitrile:0.1 M ammonium acetate (60:40) as mobile phase and detection at 254 nm, was employed. The mean correlation coefficient of the calibration curve (n = 6) for the assay was 0.9999 over a concentration range of 24.6 to 147.6 micrograms/mL of fenoverine standard solutions. Fenoverine did not decompose significantly at 4, 45, 55, and 65 degrees C for 3 months. The mean correlation coefficients of within-day and between-day calibration curves were 0.9995 and 0.9999, respectively, over a range of 10 to 1000 ng/mL of fenoverine in plasma. The limit of detection was 10 ng in plasma. PMID- 1619578 TI - Structural study of benzidamine salicylate in the solid state and in solution. AB - The vibrational (IR and Raman) and 1H and 13C NMR spectra of the analgesic and anti-inflammatory benzidamine salicylate (Benzasal) have been examined, and the results are described. The crystal structure of this compound has been determined by X-ray diffraction. To assist in interpretation of the spectroscopic data, some measurements of benzidamine, benzidamine hydrochloride, and salicylic acid have also been made. The most important intermolecular interactions of benzidamine salicylate in the solid state are N(+)H...O(-)...-C hydrogen bonds involving both salicylate oxygen atoms (d = 2.658 A and 3.228 A). At least the stronger hydrogen bond remains in CDCl3 solution. Moreover, the strong intramolecular hydrogen bond O-H...O(-)...-C within the salicylate anion has also been observed in the solid state and in solution. PMID- 1619579 TI - Independent contractors or employees. PMID- 1619580 TI - Revolutions in the evolution of American Dentistry. PMID- 1619582 TI - Alexithymia and somatic complaints in psychiatric out-patients. AB - This study investigated the prevalence of alexithymia and its relationship with somatic complaints in a sample of 118 general psychiatric out-patients. Of the sample 39.8% scored in the alexithymic range of the Toronto Alexithymia Scale. Compared with the non-alexithymic patients, the alexithymic patients scored significantly higher on several Minnesota Multiphasic Personality Inventory (MMPI) scales that collectively measure a diverse and extensive range of somatic symptoms and bodily concerns. In addition, the alexithymic patients had significantly higher levels of anxiety, depression, and general psychological turmoil. Although the alexithymic and non-alexithymic patients did not differ on the MMPI Repression and overall Hysteria Scales, which reflect the defenses of denial and repression, the alexithymic patients had significantly less ego strength and were significantly more dependent and more likely to engage in impulsive and acting out behaviours. The overall pattern of results is consistent with the view that alexithymic individuals are prone to both 'functional' somatic symptoms and symptoms of emotional turmoil because they are not well equipped psychologically. PMID- 1619581 TI - The psychosocial impact of HIV infection in men with haemophilia: controlled investigation and factors associated with psychiatric morbidity. AB - The aim of the investigation was to establish the prevalence of psychosocial problems in men with haemophilia and HIV infection, and to identify factors associated with psychological morbidity. A cross-sectional controlled study including 37 HIV seropositive and 36 HIV seronegative men with haemophilia under the care of the Oxford Haemophilia Centre were included in the investigation. The outcome measures included current psychological status (PSE, POMS, Beck Hopelessness Scale and Self-Esteem) and psychiatric history; coping and health beliefs (Self-Control Schedule, Hardiness Scale, Health Locus of Control Scale); social functioning (Modified Social Adjustment Scale); and sexual functioning. The results showed that seropositive individuals, whether symptomatic or not, had significantly worse total PSE scores and had higher levels of hopelessness. In addition, symptomatics had worse depression scores (POMS) than seronegatives. However, levels of psychiatric morbidity were generally low, even in the seropositive group. High levels of psychological morbidity were associated with high levels of hopelessness, unfavourable social adjustment, past psychiatric history and symptomatic HIV disease. Seropositives reported greater negative impact on their sex lives, and sexually active seropositives reported a significantly greater prevalence of sexual dysfunction than seronegatives. The majority of seropositives reported regular condom use during intercourse, and also continuing concerns about infecting their sexual partners in spite of it. In summary, it was found that men with haemophilia an HIV infection have higher levels of psychological distress and sexual problems than seronegatives. The skilled staff involved in their treatment are in a good position to identify their difficulties and ensure that good care is provided. PMID- 1619583 TI - The acute appendicitis syndrome: psychological aspects of the inflamed and non inflamed appendix. AB - The aetiological importance of stressful life events and psychological characteristics was assessed amongst 280 appendicectomy patients of whom 80% were classified with 'acutely inflamed' (organic) appendicitis and 20% with 'non inflamed' (non-organic) appendicitis. Patients were compared with a community comparison group. Specific characteristics of life stressors, namely severe goal frustration for organic patients and severe threat for non-organic patients, were the best predictors of patient outcome. Whilst psychological characteristics were not useful in discriminating between patients, depression in particular, was clearly associated with both conditions, with 38% of non-organic and 28% of organic patients with depression scores in the clinical range. As the patient's clinical depression status failed to modify the effect of the life stress predictors, it was concluded that life stress played an important role in the development of the patients GI symptoms, irrespective of their clinical depression status. PMID- 1619584 TI - Vital exhaustion and perception of sleep. AB - Sleep complaints and unusual sleep durations have been found to increase the risk for coronary heart disease. One explanation states that insomnia and excess fatigue on final waking are predictive for myocardial infarction because they are part of a state of 'vital exhaustion'. Sleep complaints and sleep durations, however, are usually assessed with retrospective self-report procedures. Such procedures must be interpreted with reserve because in insomniacs, a consistent disparity in the perception of habitual and current sleep has been observed. This caused us to question whether this phenomenon is present in exhausted males also. Two approaches were used. The first one consisted of a retrospective assessment of subjective sleep characteristics, the second one of self-monitoring these sleep characteristics during 21 days. In the second week, subjects slept in a laboratory. No disparity was found in how exhausted males perceive their habitual and current sleep. It appeared that sleep quality is worse and sleep duration is shorter in exhausted males. They also feel more sleepy and take longer naps during the day, indicating that their daytime functioning is impaired. Sleeping in a laboratory reduced time asleep and midsleep wake. Sleep quality, however, was essentially the same as at home. These findings made us conclude that it is not the intrusion of nocturnal wake times per se but more likely the impaired daytime functioning which is the reason for exhausted males to complain about their sleep. PMID- 1619585 TI - The impact of infertility on psychological functioning. AB - To explore the impact of infertility on psychological functioning 130 couples presenting with primary infertility were assessed at their initial visit to an infertility clinic. Of these, 116 couples were assessed on a second occasion some 7-9 months later when in most cases the medical tests were complete. Measures of personality, psychopathology, perceived social support, sex role identity and marital state were obtained from both partners. The set was subsequently divided into five subgroups on the basis of the diagnosis made or the outcome (female cause, male cause, female and male cause, unexplained and pregnant). The results show little evidence of psychopathology in the sample, depression scores remained low throughout the period of investigation. The results also indicated stable marital relationships. Scores on tests of anxiety and psychiatric morbidity declined between the first and second assessment except in the case of men who were diagnosed with a fertility problem. The implications of these findings are discussed in the increased use of donor insemination which circumvents rather than treats the problem of male infertility. PMID- 1619586 TI - The cardiac denial of impact scale: a brief, self-report research measure. AB - Denial is an important aspect of recovery from cardiac trauma. It has been associated with reduced anxiety, better initial physical and psychological outcomes, decreased retention of information about the illness, and decreased treatment compliance. Although interview methods for assessing denial have been available for some time, they present both psychometric and methodological difficulties that a self-report measure could alleviate. This study provides the initial psychometric evaluation of the self-report Cardiac Denial of Impact Scale. It demonstrated adequate internal consistency as well as good criterion and discriminant validity. The availability of a self-report measure of denial can simplify its assessment in both research and treatment applications. PMID- 1619587 TI - Contingent and non-contingent biofeedback training for Type A and B healthy adults: can Type As relax by competing? AB - This paper investigates an alternative approach to the modification of cardiovascular reactivity in healthy Type A adults using contingent (true) and non-contingent (false) heart rate biofeedback. Sixteen Type A and sixteen Type B subjects were either given instructions to compete for heart rate reduction or were given no competitive instructions. There were four relaxation sessions. In one, subjects were given contingent heart rate biofeedback and in another they were given no feedback. In two sessions 'feedback' was non-contingent: in one condition feedback suggested that heart rate decreased across the session; in the other the suggestion was of increase. Results showed that overall, biofeedback was an effective method for heart rate reduction but non-contingent feedback (decreased heart rate) was found to be as effective as contingent feedback. Overall, Type A subjects reduced heart rate significantly more than Type Bs. More importantly, Type As reduced heart rate significantly more when competing than when competition was not mentioned. These results suggest that core elements of Type A behaviour, in particular competition, could be exploited in the modification of physiological hyperactivity in healthy Type A individuals. PMID- 1619588 TI - Psychiatric morbidity in a gynaecology clinic in Nigeria. AB - Psychological disorders among 233 women attending a gynaecology out-patient clinic was assessed by a two-stage screening procedure, using the GHQ-30 and the PSE. The prevalence of psychiatric disorders was found to be 35.2%. Psychiatric morbidity was significantly associated with a history of induced abortion, previous marriages, having no children, complaints of menstrual abnormalities, chronic pelvic pain and having unsupportive husbands. It is suggested that more attention needs to be paid to the psychological health of patients with gynaecological disorders (in line with the biopsychosocial model of health care). This will ensure an overall improvement in the quality of care. PMID- 1619589 TI - Denial mechanisms in myocardial infarction: their relations with psychological variables and short-term outcome. AB - From a selected sample of 97 males suffering from a first myocardial infarction, 67 patients were studied to ascertain the influence of denial mechanisms (DM) on their cardiological and psychological outcome. There were no differences among high deniers and low deniers with respect to the cardiological outcome, but high deniers showed less anxiety and depressive reactions both in the coronary unit and 1 month later, and also presented less psychopathology in general. In the last evaluation, one year after leaving the hospital (N = 52), there was no difference among deniers and non deniers in demand for psychiatric attention. PMID- 1619590 TI - Stress-induced changes in the rate of sodium excretion in healthy black and white men. AB - The effects of exposure to competitive mental stressors on rates of excretion of sodium (Na), potassium (K) and fluid, together with cardiovascular responses, were evaluated in 14 black and 14 white normotensive men after 3 days of controlled diet (200 mEq Na, 100 mEq K daily). In the first hour of a 5-hr protocol, subjects ingested a standard dinner and drank 1 liter of water. In hours 2-5, they voided to provide urine collections every 30 min, and drank 200 ml additional water after each collection. Hours 1-2 were for stabilization of excretion, hour 3 was baseline, hour 4 was stress and hour 5 was post-stress rest. During stress, 20 men showed faster natriuresis and 8 showed slower natriuresis than at baseline. These subgroups did not differ in any excretion measure at baseline. During stress, the slow stress natriuresis group showed slower excretion of potassium and fluid as well as sodium; slow natriuresis and kaliuresis persisted 30 min after stress. Creatinine clearance rate was also decreased, but only during the first 30 min of stress. Slow stress natriuresis subjects were found to have higher blood pressures during baseline and stress, greater heart rate and cardiac output increases during stress, and a larger percentage had hypertensive parents (63 vs 37%) compared to fast stress natriuresis subjects. Slow stress natriuresis was observed in 50 vs 17% of men with resting diastolic levels above vs below 80 mmHg, and in 43% of blacks vs 18% of whites tested. Overall, black subjects tended to excrete sodium more slowly than whites at baseline, and showed significantly lesser increases in sodium excretion rate when pressures rose during stress. PMID- 1619592 TI - Respiratory distress resulting from acute lung injury in the veterinary patient. AB - Because of improved management of animals in intensive care facilities, veterinarians are often confronted with patients at risk of developing adult respiratory distress syndrome (ARDS). The four objectives of this review are: 1) to describe the clinical conditions which place animals at risk for development of ARDS, 2) to give the reader a comprehensive understanding of the pathophysiology of endotoxin-induced lung injury, 3) to address the interspecies variability in susceptibility to endotoxin-induced lung injury, and 4) to outline areas where veterinarians should be concentrating their diagnostic and therapeutic efforts with regards to this syndrome. Because there is little written in the veterinary literature on ARDS, this review will rely heavily on the human ARDS literature as well as on research in animal models of acute lung injury. PMID- 1619591 TI - Canine bladder and urethral tumors: a retrospective study of 115 cases (1980 1985). AB - One hundred and fifteen dogs with neoplasms of the lower urinary tract (bladder and/or urethra) were retrospectively evaluated at five referral institutions participating in ongoing studies by the Veterinary Cooperative Oncology Group. Most tumors were malignant (97%) and of epithelial origin (97%). Lower urinary tract tumors were more common in older dogs weighing greater than 10 kg. The following significant (P less than 0.05) statistical associations were found using the University of Guelph hospital population as control; there was no sex predisposition although the female:male ratio was 1.95:1. Neutered dogs were predisposed as were Airedale Terriers, Beagles, and Scottish Terriers, whereas German Shepherds were significantly under-represented among dogs with lower urinary tract tumors. These statistical associations should be interpreted cautiously because of possible demographic differences in hospital populations among the University of Guelph and other cooperating institutions. There were no significant correlations between age, gender, weight, breed, response to therapy, and survival time. Clinical signs were indicative of lower urinary tract disease and included hematuria, stranguria, and pollakiuria. The laboratory data were nonspecific except for urinalysis test results. Hematuria and inflammatory urinary sediments were most commonly reported; neoplastic cells were identified in the urine sediment of 30% of dogs with lower urinary tract tumors. Contrast cystography was a useful noninvasive diagnostic method since 96% of the dogs had a mass or filling defect in the lower urinary tract demonstrated by this technique.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619593 TI - Unilateral and bilateral brainstem auditory-evoked response abnormalities in 900 Dalmatian dogs. AB - In a survey of 900 Dalmatian dogs, brainstem auditory-evoked responses (BAER) and clinical observations were used to determine the incidence and sex distribution of bilateral and unilateral BAER abnormalities and their association with heterochromia iridis (HI). To assess the efficacy of BAER testing in guiding breeding programs, data from 749 dogs (subgroup A), considered to be a sample of the population at large, were compared with data from a subgroup (subgroup B; n = 151) in which selection of breeding stock had been based on BAER testing from the beginning of the 4-year survey. Brainstem auditory-evoked responses were elicited by applying click stimuli unilaterally, while applying a white noise masking sound to the contralateral ear. Under these conditions, BAER were either normal, unilaterally absent, or bilaterally absent. Dogs with bilaterally absent BAER were clinically deaf; dogs with unilaterally absent BAER were not clinically deaf but appeared dependent on their BAER-normal ears for their auditory-cued behavior. Dogs with unilaterally absent BAER often were misidentified as normal by uninformed observers. Among the 900 dogs, 648 (72.0%) were normal, 189 (21.0%) had unilateral absence of BAER, and 63 (7.0%) had bilateral absence of BAER or were clinically deaf and assumed to have bilaterally absent BAER (n = 4). Total incidence in the population sampled was assumed to be higher, because some bilaterally affected dogs that would have been members of subgroup A undoubtedly did not come to our attention. Among females, 24.0% were unilaterally abnormal and 8.2% were bilaterally abnormal whereas, among males, 17.8% were unilaterally abnormal and 5.7% were bilaterally abnormal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619594 TI - Brainstem auditory-evoked potential assessment of congenital deafness in Dalmatians: associations with phenotypic markers. AB - To screen for congenital deafness, brainstem auditory-evoked potential (BAEP) testing was performed on 1031 Dalmatians from three geographically separated areas. Phenotypic marker assessment was done to determine markers possibly associated with deafness. Markers included sex, hair coat color, pigmentation of different areas of skin (eye rims, nose, and ears), presence of a patch, spot size and marking (density of spotting), sire and dam BAEP status, and presence of iris and retinal tapetal pigmentation. Combined data from all test sites showed 8.1% bilateral deafness (N = 83 dogs) and 21.6% unilateral deafness (N = 223), or an overall 29.7% incidence of hearing disorders. Significant (P less than 0.05) associations with deafness for the data from all test sites combined were seen for patch, sire and dam BAEP, iris pigment, and retinal pigment. However, results differed for several of the significant phenotypic markers when analyses were done on the data from the individual test sites; changes from significant to not significant were found. This suggested the existence of multiple populations of deafness patterns, and reinforced the precautionary conclusion that associations of phenotypic markers with deafness are not necessarily functionally significant. PMID- 1619595 TI - Post-transfusion survival of 50Cr-labeled erythrocytes in neonatal foals. AB - Erythrocytes transfused allogeneically into mature horses have a short survival (less than 4 days) compared with an expected erythrocyte life span of 140-150 days. Yet, foals undergo transfusions for neonatal isoerythrolysis successfully. The authors have determined the survival of transfused erythrocytes in neonatal foals, using the stable isotope, 50Cr, to label the erythrocytes. Normal foals underwent transfusions with labeled erythrocytes from three sources: their own erythrocytes (autologous), the erythrocytes of their dam, and the erythrocytes of an unrelated castrated male. After transfusion, samples were taken at 15 minutes and then daily for a week and every 2 or 3 days for 20 days. A stable isotope of iron (57Fe) and 50Cr were determined on diluted-packed erythrocytes by inductively coupled argon-coupled mass spectrometry techniques. 57Fe was used as measure of the sample hemoglobin concentration. The ratio of 50Cr to 57Fe decreased exponentially in all foals. Half-time (T1/2) was 11.7 days (standard error = 2.2) for four foals that underwent autologous transfusions, 5.5 +/- 1.0 days for five foals that underwent transfusions with the erythrocytes of their dams, and 5.2 +/- 1.1 days for five foals that had transfusions with erythrocytes from an unrelated gelding. The authors conclude that erythrocytes that are transfused allogenically into neonatal foals will survive longer than those transfused into mature horses and that 50Cr labeling can be used to measure survival of transfused erythrocytes. PMID- 1619596 TI - A review of disorders of the gallbladder and extrahepatic biliary tract in the dog and cat. AB - Disorders of the gallbladder and extrahepatic biliary tract in the dog and cat can easily be confused with other intra-abdominal disorders. This confusion results because many times the clinical course and signs of biliary tract disease are similar to these other intra-abdominal disorders. This review discusses the normal anatomy and physiology of the gallbladder, bile duct, and bile in the dog and cat and then summarizes the historic, physical examination, clinicopathologic, diagnostic, histologic and therapeutic aspects of all the cases of extrahepatic biliary tract disease reported in the veterinary literature. PMID- 1619597 TI - Failure of passive transfer in foals. PMID- 1619598 TI - Hepatic organelle pathology in dogs with CPSS. PMID- 1619600 TI - Cervex-Brush and Cytobrush: comparison of their ability to sample abnormal cells for cervical smears. PMID- 1619599 TI - Intrapleural administration of cisplatin (DDP) for treatment of pleural neoplasia. PMID- 1619601 TI - Traditional and molecular cytogenetics. AB - Traditional cytogenetic methods have relied on tissue culture techniques to generate adequate mitotic cells for the analysis of chromosome disorders for prenatal diagnosis. Chromosome banding techniques allow the evaluation of mitotic cells for structural and numerical aberrations and define the nature of any rearrangement. With the advent of fluorescent in situ hybridization methodology, which combines the molecular technologies of chromosome-specific probes and in situ molecular hybridization, it has become possible to analyze chromosomal numerical and structural aberrations from interphase cells. The use of molecular cytogenetic techniques should greatly increase the speed and diagnostic resolution of clinical specimens. PMID- 1619602 TI - TORCH infections. Diagnosis in the molecular age. AB - TORCH agents cause a varied spectrum of disease. Advances in ultrasound, invasive perinatal procedures and molecular diagnostics have allowed in utero evaluation. Infected fetuses, especially those which are sonographically abnormal, may be treated in utero depending upon the pathogen and attendant pathophysiology. Subclinical perinatal infections may lead to later childhood deficits. Such infected fetuses may benefit from early diagnosis and prompt initiation of rehabilitative measures. PMID- 1619603 TI - Prospects for human gene therapy. AB - Retroviral vectors containing marker genes and the sequence for human proteins have been used to transduce cultured lymphocytes, which have then been reinfused into patients. Circulating hematopoietic progenitor cells from human fetal cord blood obtained at the time of term and premature deliveries as early as 19 weeks of gestation have been shown to express such transduced genes in vitro. Cord blood cells from fetal sheep sampled and transduced ex vivo and transfused back in utero expressed marker genes up to two years after birth. Although the efficiency of gene transfer into cells and their long-term expression need to be improved, the potential exists for treating some genetic diseases after prenatal diagnosis either in utero or shortly after birth. PMID- 1619604 TI - In utero stem cell therapy. AB - In utero stem cell transplantation offers the potential for treating a number of genetic disorders. The combination of fetal immunotolerance and fetal marrow space makes the fetus an excellent transplant recipient. Experiments on the mouse, sheep and rhesus monkey have indicated that in utero transplantation is feasible. Human trials are currently beginning. PMID- 1619605 TI - Legal and ethical issues arising from the new genetics. AB - Legal and ethical issues involving genetics arise at the level of carrier screening, preimplantation diagnosis in embryos and prenatal diagnosis in fetuses. A strong commitment to procreative liberty and autonomy should permit patients and physicians to gain access to genetic information at every stage of decision making. Even if Roe v Wade is reversed, considerable room for the use of genetic information in procreative decision making will remain. PMID- 1619606 TI - Endothelium-derived relaxation of the pregnant and nonpregnant canine uterine artery. AB - Vascular responses to acetylcholine (ACh) and the calcium ionophore A23187 were studied in rings of pregnant and nonpregnant canine uterine arteries. Segments were fixed vertically in Krebs-Henseleit solution, and isometric tension was measured with force-displacement transducers. In nonpregnant canine artery preparations precontracted to a stable plateau tension with norepinephrine, ACh and A23187, dose-dependent relaxation was elicited in intact rings but not in endothelium-denuded rings. This endothelium-dependent relaxation was not affected by pretreatment with indomethacin but was inhibited by pretreatment with lipoxygenase inhibitors, nordihydroguaiaretic acid and the selective 5 lipoxygenase inhibitor AA861. Therefore, relaxation appeared to be mediated by a noncycloxygenase metabolite or metabolites. Similar endothelium-dependent relaxation was also observed in pregnant canine artery preparations. The results indicate that an endothelium-derived relaxing factor might play a physiologic role in maintaining the blood flow of the uterine circulation. PMID- 1619607 TI - Laser vaporization conization. AB - Laser vaporization conization is a modified technique for the diagnosis and treatment of cervical intraepithelial neoplasia. Two circles are marked on the cervix with the laser; the inner circle outlines the circumference of the conization specimen, while the outer one outlines an area 3 mm peripheral to all colposcopically abnormal tissue. The area between the circles is vaporized to 7 mm. This initial vaporization allows easier manipulation of the conization specimen. Laser conization is then performed. This technique is significantly easier to perform than laser excisional conization or combination excisional vaporization conization and thus is ideal for teaching residents laser conization. Besides ease of performance, laser vaporization conization retains the advantages of laser vaporization and provides a specimen for pathologic review. In this study the median laser time was 14 minutes. There was minimal operative hemorrhaging, and only one patient (2%) developed a secondary cervical hemorrhage. A significant laser artifact was present in one case (2%). One case of invasive squamous cell cancer was diagnosed. PMID- 1619608 TI - Confusion of trimester and viability. Consequences for abortion laws in the United States and abroad. AB - The present U.S. abortion law, Roe v Wade, is based on the trimester/viability concept. However, both concepts seem to be biologically ill founded and are likely to contribute to confusion regarding abortion laws. A survey of the abortion laws in individual states revealed a lack of uniformity. The time limit for abortion upon request varies from 13 to 28 weeks; nine states have no specific abortion law. This confusion also exists in other countries. Standards are lacking regarding requests for the dates of the last menstrual period, fertilization and implantation. Some states do not allow termination of pregnancy for maternal indications after 24 weeks, and the definition of maternal endangerment has rarely been addressed and remains vague. Only a few states have provisions for fetal malformation. Such terms as trimester and viability are not biologically founded and are likely to contribute to the confusion. The terminology should be clarified so abortion, contraception, birth control and other such terms are uniform. PMID- 1619609 TI - Characteristics of second labor occurring 10 or more years after the first. AB - Labor characteristics in 89 women undergoing a second vaginal delivery 10-18 years after the first were compared retrospectively with those of 136 women with an interval of 1-4 years between their first and second vaginal deliveries and with those of 128 nulliparous women. The pelvic findings on admission, average length of stages 1 and 2 of labor, average cervical dilation per hour and rates of surgical intervention in relation to arrest disorders were similar in the two multiparous groups and significantly different from these parameters in the nulliparous group. Women with long intervals between their first and second vaginal deliveries should be managed in the same way as are other multiparas and not like nulliparas with respect to such issues as indications for oxytocin treatment, surgical intervention and use of conduction anesthesia. PMID- 1619610 TI - Value of subcutaneous and intravenous pulsatile gonadotropin releasing hormone in polycystic ovary disease. AB - Nine patients with clomiphene-resistant polycystic ovary disease (PCOD) were treated with pulsatile gonadotropin releasing hormone (GnRH). The patients were started on subcutaneous (SC) GnRH. If they failed to ovulate on SC therapy, intravenous (IV) therapy was administered. Nine patients were treated for a total of 22 cycles; 13 were SC and 9, IV. There were nine ovulatory cycles (41%); four were SC (31%) and five, IV (56%). Two conceptions occurred, both among the IV cycles. One conception was a singleton; the infant was delivered uneventfully at term. The second conception was quadruplets, with the delivery of four healthy infants at 36 weeks. These data suggest that ovulation and conception in clomiphene-resistant PCOD patients using pulsatile GnRH are more likely to occur after IV than SC administration. However, the overall pregnancy rate was not greater than with gonadotropin treatment, and the risk of multiple births after IV administration is potentially high. PMID- 1619611 TI - Conservative management of splenic subcapsular hematoma in the third trimester of pregnancy. A case report. AB - A delayed splenic hemorrhage from a subcapsular hematoma occurred in association with pregnancy. That rare complication carries a high mortality rate, is rarely diagnosed preoperatively and is correctly diagnosed only 20% of the time. The clinical setting and a high index of suspicion led us to investigate for the presence of a splenic hematoma. A computed tomographic scan was invaluable in establishing the diagnosis. We adopted a conservative approach and followed the patient's clinical course from 28 to 40 weeks' gestation, until she delivered vaginally. In general, patient management (conservative vs. splenectomy) and mode of delivery will depend on how close one is to the initial event, on the patient's and fetus's clinical condition and on the gestational age. PMID- 1619612 TI - Vulvar cicatricial pemphigoid as a lichen sclerosus imitator. A case report. AB - Because vulvar lichen sclerosus is very common, a clinician confronted with hypopigmentation and agglutination of the labia minora is tempted to make a diagnosis of the disease without the benefit of a skin biopsy or a careful examination of other epithelial surfaces. Unfortunately, that clinical picture is also consistent with the end stage of several other diseases, including cicatricial pemphigoid (benign mucous membrane pemphigoid), as demonstrated by a case of cicatricial pemphigoid affecting the vulva. PMID- 1619613 TI - Antepartum fetomaternal hemorrhage. Report of a case with the use of cordocentesis in diagnosis and management. AB - Clinical recognition of antepartum fetomaternal hemorrhage (FMH) is most often achieved by the observation of characteristic fetal heart rate (FHR) patterns and positive Kleihauer-Betke acid elution staining. Both methods are noted to lack sensitivity and specificity. A case of suspected antepartum FMH occurred with intermittent sinusoidal FHR tracings. Fetal blood sampling by cordocentesis in situations with equivocal antenatal testing, such as in this case, allows not only confirmation of fetal anemia but assessment of fetal acid-base status. In pregnancies of less than 32 weeks' gestation complicated by severe antepartum FMH, intravascular transfusion may be offered via this technique. Cordocentesis is beneficial in the management of pregnancies with uncertain FHR patterns when antepartum FMH is suspected. PMID- 1619614 TI - Synthesis and anti-HIV activity of isonucleosides. AB - A series of isomeric 2',3'-dideoxynucleosides which contains a modified carbohydrate moiety has been prepared. This class of compounds was designed to mimic the activity of known anti-HIV dideoxynucleosides, while imparting enhanced chemical and enzymatic stability. Isonucleosides containing the standard heterocyclic bases (A, C, G, T) were synthesized via nucleophilic addition of the base to an isomeric sugar unit. Modified derivatives were generated by manipulation of the intact isonucleoside. Two of the compound prepared, iso-ddA (1) and iso-ddG (6), exhibit significant and selective anti-HIV activity, as well as beneficial hydrolytic stability. PMID- 1619615 TI - 2-Alkynyl derivatives of adenosine and adenosine-5'-N-ethyluronamide as selective agonists at A2 adenosine receptors. AB - In the search for more selective A2-receptor agonists and on the basis that appropriate substitution at C2 is known to impart selectivity for A2 receptors, 2 alkynyladenosines 2a-d were resynthesized and evaluated in radioligand binding, adenylate cyclase, and platelet aggregation studies. Binding of [3H]NECA to A2 receptors of rat striatal membranes was inhibited by compounds 2a-d with Ki values ranging from 2.8 to 16.4 nM. 2-Alkynyladenosines also exhibited high affinity binding at solubilized A2 receptors from human platelet membranes. Competition of 2-alkynyladenosines 2a-d for the antagonist radioligand [3H]DPCPX and for the agonist [3H]CCPA gave Ki values in the nanomolar range, and the compounds showed moderate A2 selectivity. In order to improve this selectivity, the corresponding 2-alkynyl derivatives of adenosine-5'-N-ethyluronamide 8a-d were synthesized and tested. As expected, the 5'-N-ethyluronamide derivatives retained the A2 affinity whereas the A1 affinity was attenuated, resulting in an up to 10-fold increase in A2 selectivity. A similar pattern was observed in adenylate cyclase assays and in platelet aggregation studies. A 30- to 45-fold selectivity for platelet A2 receptors compared to A1 receptors was found for compounds 8a-c in adenylate cyclase studies. PMID- 1619616 TI - Substituent variation in azabicyclic triazole- and tetrazole-based muscarinic receptor ligands. AB - The effect of variation of the 1-azabicyclic substituent on the novel 1,2,3 triazol-4-yl-, 1,2,4-triazol-1-yl, tetrazol-5-yl-, and tetrazol-2-yl-based muscarinic receptor ligands has been studied, and the exo-azabicyclic[2.2.1]hept 3-yl substituent was found to give the most potent and efficacious compounds. In addition, variation of the second substituent on 1,2,4-triazol-1-yl- and tetrazol 2-yl-based muscarinic receptor ligands has yielded a series of novel compounds with high potencies and efficacies, ranging from full agonists to antagonists. Small lipophilic electron withdrawing substituents give potent but low efficacy compounds, while small polar electron donating substituents give potent and efficacious compounds. The activity of these compounds is described in terms of a model of the receptor involving lipophilic and hydrogen bonding interactions. These compounds provide muscarinic ligands with high potency and a range of efficacies suitable for testing as candidate drugs in the treatment of Alzheimer's disease. PMID- 1619617 TI - Inhibition of N8-acetylspermidine deacetylase by active-site-directed metal coordinating inhibitors. AB - A number of substrate analogues of N8-acetylspermidine (N8-AcSpd) (16) and chemical modifying agents containing metal coordinating ligands were assayed as inhibitors of the cytoplasmic enzyme N8-AcSpd deacetylase from rat liver. The enzyme is inhibited by metal chelators, several omega-amino-substituted carboxylic acids, and some thiol reagents. Inhibition by diisopropyl fluorophosphate was observed only at high concentrations. These results suggest that the catalytic mechanism of the enzyme requires a transition state metal and free sulfhydryl groups for activity. The most potent inhibitor synthesized 6-[(3 aminopropyl)amino]-N-hydroxyhexanamide (15), has an apparent Ki of 0.001 microM. It binds to the target enzyme 11,000 times tighter than the substrate (apparent Km = 11 microM). These compounds and a previously reported series of compounds (Dredar, S. A.; Blankenship, J. W.; Marchant, P. E.; Manneh, V. A.; Fries, D. S. J. Med. Chem. 1989, 32, 984-989) are useful in mapping the active site and determining the physiological function of N8-AcSpd deacetylase. PMID- 1619618 TI - Quantitative structure-activity relationships of benzamide derivatives for anti leukotriene activities. AB - To determine the structural requirements of the benzamide derivatives reported by Nakai et al. (J. Med. Chem. 1988, 31, 84-91) for antileukotriene activity, we studied their conformational characteristics in comparison with those of leukotriene. By superimpositions of the conformations of antagonists on that of leukotriene, we found that the conformations of the conjugated benzamide moiety, tetrazole ring, and benzopyran or benzodioxan ring of the antagonists correspond to the triene moiety, peptide carboxylic acid residue, and cysteine residue of leukotriene, respectively, but that no moiety of the antagonists corresponds to the terminal aliphatic carboxylic acid moiety of leukotriene. Furthermore, the stable conformations of alkyl and alkoxy groups of the antagonists were quite different from that of the omega-chain of leukotriene. However, conformational analyses taking all the possible rotations of these flexible chains into consideration showed that antagonists in which these flexible chains can most feasibly adopt the same lengths as those of the omega-chain exhibit potent antagonist activity. From these results, we deduced the structural features of benzamide derivatives necessary for potent antileukotriene activity. PMID- 1619619 TI - Structure-activity relationship in the gastric cytoprotective effect of several sesquiterpene lactones. AB - The structural requirements for the gastric cytoprotective activity of several sesquiterpene lactones are reported. A theoretical-experimental study on the potentially active centers is carried out. The biological evaluation of reduced analogues and the simulation of the molecular interactions between these compounds and an endogenous cysteine residue suggest that the presence of a non sterically hindered Michael acceptor seems to be an essential structural requirement for the cytoprotective activity in this family of compounds. This observation suggests that cytoprotection is mediated through a Michael reaction between the sulfhydryl-containing peptides of the mucosa and Michael acceptors present in the molecules under study. This mechanism of action is in addition to and distinct from the one proposed in our previous paper, namely, that these sesquiterpenes stimulate endogenous synthesis of prostaglandins. PMID- 1619620 TI - Extraordinarily potent antimalarial compounds: new, structurally simple, easily synthesized, tricyclic 1,2,4-trioxanes. AB - New, racemic, tricyclic trioxane alcohol 3 was designed and synthesized as a structurally simple analog of clinically useful, tetracyclic, antimalarial artemisinin. A series of 20 ester and ether derivatives of alcohol 3 were prepared easily, without destruction of the essential trioxane system. Chemical structure-antimalarial activity for each derivative was evaluated in vitro against chloroquine-resistant and chloroquine-sensitive Plasmodium falciparum parasites. Many of these derivatives were highly efficacious; carboxylate ester 9f, carbamate ester 10a, and sulfonate ester 12a had antimalarial potency similar to that of artemisinin, and carboxylate esters 9b and 9d, carbamate esters 10b and 10c, and phosphate esters 11a-c had antimalarial potency up to 7 times higher than that of artemisinin. Several of these most active analogs (e.g., carboxylate 9b and carbamates 10a and 10c) are stable crystalline solids, a feature of considerable practical value for any new drug candidate. PMID- 1619621 TI - Novel sulfonamides as potential, systemically active antitumor agents. PMID- 1619622 TI - Isopropyl and phenyl esters of 3 beta-(4-substituted phenyl)tropan-2 beta carboxylic acids. Potent and selective compounds for the dopamine transporter. PMID- 1619623 TI - Unprincipled QALYs: a response to Harris. PMID- 1619624 TI - No-fault compensation for victims of non-therapeutic research--should government continue to be exempt? PMID- 1619625 TI - Health care ethics and casuistry. PMID- 1619626 TI - On lying and deceiving. AB - This article challenges Jennifer Jackson's recent defence of doctors' rights to deceive patients. Jackson maintains there is a general moral difference between lying and intentional deception: while doctors have a prima facie duty not to lie, there is no such obligation to avoid deception. This paper argues 1) that an examination of cases shows that lying and deception are often morally equivalent, and 2) that Jackson's position is premised on a species of moral functionalism that misconstrues the nature of moral obligation. Against Jackson, it is argued that both lying and intentional deception are wrong where they infringe a patient's right to autonomy or his/her right to be treated with dignity. These rights represent 'deontological constraints' on action, defining what we must not do whatever the functional value of the consequences. Medical ethics must recognise such constraints if it is to contribute to the moral integrity of medical practice. PMID- 1619627 TI - Attitudes of a Mediterranean population to the truth-telling issue. AB - The attitudes of the Greeks, a Mediterranean population, to the issue of telling the truth to the patient have been studied. There is no clear answer to the question: 'Do the Greeks wish to be informed of the nature of their illness?'. The answer is: 'It depends'. It depends on age, education, family status, occupation, place of birth and residence and on whether or not they are religious people. However, it does not depend on their sex--men and women have similar reactions to the issue of truth-telling. Although the present study shows lower percentages of those who wish to know the truth than studies on other populations, the conclusion is that, emphasising the need for good communication between doctors and patients, doctors should not lie, but should disclose to their patients the part of the truth they are ready to accept. PMID- 1619629 TI - A proposal to classify happiness as a psychiatric disorder. AB - It is proposed that happiness be classified as a psychiatric disorder and be included in future editions of the major diagnostic manuals under the new name: major affective disorder, pleasant type. In a review of the relevant literature it is shown that happiness is statistically abnormal, consists of a discrete cluster of symptoms, is associated with a range of cognitive abnormalities, and probably reflects the abnormal functioning of the central nervous system. One possible objection to this proposal remains--that happiness is not negatively valued. However, this objection is dismissed as scientifically irrelevant. PMID- 1619628 TI - The psychological profile of parents who volunteer their children for clinical research: a controlled study. AB - Three standard psychometric tests were administered to parents who volunteered their children for a randomised, double-blind placebo-controlled trial of a new asthma drug and to a control group of parents whose children were eligible for the trial but had declined the invitation. The trial took place at a children's hospital in Australia. The subjects comprised 68 parents who had volunteered their children and 42 who had not, a participation rate of 94 per cent and 70 per cent, respectively. The responses of these parents to the Gordon Survey of Interpersonal Values Questionnaire, the Coopersmith Self-Esteem Inventory and the Cattell Sixteen Personality Factor Questionnaire were analysed by computer. There was a marked difference between the psychological profiles of the two groups of parents. Volunteering parents put more value on benevolence while non volunteering parents were more concerned with power and prestige. The self-esteem of volunteering parents was much lower than that of non-volunteering parents. Finally, volunteering parents were more introverted, exhibited greater anxiety and low supergo, while non-volunteering parents appeared to have greater social confidence and emotional stability. Since an individual's values, self-esteem and personality may be important antecedents of behaviour, these findings suggest that parents who volunteer their children for clinical research are not only socially disadvantaged and emotionally vulnerable, but may also be psychologically predisposed to volunteering. Furthermore, these findings provide evidence for the existence of a psychosocial 'filter' effect of the informed consent procedure, which may be discouraging the better educated, more privileged and psychologically resilient members of society from participation as research subjects. PMID- 1619630 TI - Resource allocation--what is the first priority? PMID- 1619631 TI - Experience with direct molecular diagnosis of fragile X. AB - The utility of the pfxa3 probe for direct molecular diagnosis of the fragile X (FRAXA) has been established. This probe detects amplification of an unstable DNA element consisting of variable length CCG repeats. The size of the amplified fragment is correlated with phenotype and was determined using PstI digested DNA in family members. In 35 families with the fragile X, there was correspondence in 183 cases between the presence of an amplified unstable element and the presence of the fragile X chromosome independently determined by cytogenetics, position in the pedigree, or linked DNA markers flanking the fragile X. There was also correspondence in 124 cases between the presence of the normal 1.0 kb PstI fragment and absence of the fragile X chromosome independently determined by linked flanking markers. Six additional families considered to be isolated cases of 'fragile X' had been diagnosed before recognition of FRAXD. The pfxa3 probe confirmed the cytogenetic diagnosis in three families, the other three being rediagnosed as non-fragile X. A further two families had consistent expression of a different folate sensitive fragile site, FRAXE, close to FRAXA but not associated with fragile X syndrome and not detectable with the pfxa3 probe. Subsequent referrals were received from additional family members or from members of new families for whom carrier status had not been predetermined by linked markers. Direct pfxa3 diagnosis for the 135 females within these 222 additional cases was confirmed by dosage analysis with the control probe pS8.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619632 TI - Detection and characterisation of an overmodified type III collagen by analysis of non-cutaneous connective tissues in a patient with Ehlers-Danlos syndrome IV. AB - The clinical and biochemical observations in a patient with a mild form of Ehlers Danlos syndrome (EDS) type IV are described. The patient's skin fibroblasts produced markedly diminished amounts of type III collagen. SDS-polyacrylamide gel electrophoresis of collagens produced by cells obtained from other, non-cutaneous tissues showed two forms of collagen alpha 1(III) chains, a normal and a slow migrating, mutant form. Further analysis confirmed that the type III collagen molecules containing mutant alpha chains which were overmodified had a lower thermal stability and were poorly secreted into the extracellular medium. The protein defect was mapped by in situ cyanogen bromide digestion and was located in alpha 1(III) CB9, the C-terminal peptide of the collagen triple helix. This study shows that non-cutaneous connective tissues can be a useful source for the study of type III collagen defects in patients with EDS type IV. PMID- 1619633 TI - Limb-girdle type muscular dystrophy in a large family with distal myopathy: homozygous manifestation of a dominant gene? AB - A family study was carried out to clarify the problem of two separate muscle disease phenotypes in a large consanguineous pedigree. These were a severe limb girdle type muscular dystrophy and a mild late onset distal myopathy. Thirty-two first degree and 14 other relatives of 18 previously examined index patients were available for clinical examination. Twenty-three subjects underwent computed tomography of the lower leg muscles. No new cases of limb-girdle type muscular dystrophy were found. Distal myopathy was diagnosed in 14 subjects, 10 first degree relatives and four other relatives. Segregation analysis showed that the corrected proportion of affected with the severe proximal type was 0.246 and the proportion of affected with the distal myopathy was 0.58. Pedigree analysis is compatible with the possibility that the mild, late onset distal myopathy is caused by a dominant gene and that the limb-girdle type may be expressed in homozygotes. PMID- 1619634 TI - Use of oocytes from anonymous, matched, fertile donors for prevention of heritable genetic diseases. AB - Heritable genetic diseases can be prevented with the use of donor oocytes. We report our experience in using donor oocytes from anonymous, matched, fertile donors in four women with heritable genetic disorders. Our results show that use of donor oocytes is a practical, successful, and currently available technique for the prevention of genetic disorders. PMID- 1619635 TI - A complex rearrangement associated with sex reversal and the Wolf-Hirschhorn syndrome: a cytogenetic and molecular study. AB - We report a male infant referred with multiple congenital abnormalities consistent with the Wolf-Hirschhorn syndrome. Cytogenetic analysis showed a chromosome complement of 46,XX with a deletion of 4p15.2----4pter and its replacement by material of unknown origin. The patient was positive for a number of Yp probes including SRY, the testis determining factor, and in situ hybridisation localised the Yp material to the tip of the short arm of one X chromosome. Using pDP230, a probe for the pseudoautosomal region, and M27 beta, which recognises a locus in proximal Xp, the material translocated on to 4p was identified as originating from the short arm of the paternal X chromosome. The most reasonable explanation for this complex rearrangement is two separate exchange events involving both chromatids of Xp during paternal meiosis. An aberrant X-Y interchange gave rise to the sex reversal and an X;4 translocation resulted in additional, apparently active Xp material and a deletion of 4p which produced the Wolf-Hirschhorn phenotype. PMID- 1619636 TI - Distal 8p deletion (8p23.1----8pter): a common deletion? AB - The clinical manifestations and cytogenetic details of five patients with a de novo deletion of the short arm of chromosome 8, del(8)(p23), are described. Of the four surviving children all had mild mental retardation and subtle facial anomalies; three of the five had cardiac abnormalities. The clinical features seen in these patients are compared with those of three previous single case reports with del(8)(p23), and with patients described as having the '8p-' syndrome associated with del(8)(p21). The findings in these patients suggest that major congenital anomalies, especially congenital heart defects, are frequent even in small distal 8p deletions, but facial dysmorphism may be subtle and mental retardation less severe than in those with deletions associated with more proximal breakpoints. The five patients were detected within a four year period, suggesting that this deletion syndrome is relatively frequent. The possible mechanisms for the formation of terminal deletions are discussed. PMID- 1619637 TI - Angelman syndrome. PMID- 1619638 TI - Acromegaloid facial appearance (AFA) syndrome: report of a second family. AB - A family is reported in which the 'acromegaloid facial appearance' (AFA) phenotype was segregating through two generations. The five affected persons showed a striking resemblance to the patients previously reported, including progressively coarse acromegaloid-like facial appearance, narrow palpebral fissures, bulbous nose, and thickening of the lips and intraoral mucosa, resulting in exaggerated rugae and frenula. These patients also had increased birth weight and dull mentality. It is unclear if the differences between the two families mark distinct syndromes or simply extend the AFA phenotype. PMID- 1619639 TI - An infant with multiple congenital abnormalities and biochemical findings suggesting a variant of galactosialidosis. AB - A female newborn probably with a variant form of galactosialidosis is described. The patient, in addition to the common findings seen in early infantile forms of classical galactosialidosis, displayed an unusual combination of congenital malformations including complex cyanotic congenital heart disease with dextrocardia and situs inversus. PMID- 1619640 TI - The 3-M syndrome: risk of intracerebral aneurysm? AB - We describe a child with typical features of the 3-M syndrome who presented with acute hydrocephalus owing to haemorrhage from one of two intracranial cerebral vascular aneurysms. We suggest that other children with this disorder should be screened for similar complications. PMID- 1619641 TI - Cardiofaciocutaneous syndrome with new ectodermal manifestations. AB - We describe a 7 year old girl whose features satisfy the diagnosis of cardiofaciocutaneous syndrome. Her ectodermal features consist of fine, sparse hair, thin, opalescent nails, finger tip pads, generalised pigmentation of the skin, but no hyperkeratosis. Skin pigmentation and finger tip pads have not been previously reported in this syndrome. Twenty-two cases of CFC have been described but there is debate as to whether it is distinct from Noonan syndrome. PMID- 1619642 TI - Recurrence of orbital cysts in the branchio-oculo-facial syndrome. AB - Two sibs with the branchio-oculo-facial syndrome are reported. They both have orbital haemangiomatous cysts, which is a previously unreported feature. Both parents are clinically normal and unrelated. This disorder has been reported showing autosomal dominant transmission so this family could represent either an autosomal recessive form or germline mosaicism for the dominant gene. PMID- 1619643 TI - Two sibs with Wiedemann-Rautenstrauch syndrome: possibilities of prenatal diagnosis by ultrasound. AB - A girl with Wiedemann-Rautenstrauch syndrome was born to a non-consanguineous couple. During the pregnancy, growth retardation particularly in the biparietal and abdominal diameters but not the femoral length was detected through serial ultrasound scans. When the woman became pregnant again, in spite of having been assessed as having a 25% risk of recurrence, the prenatal findings seen in her previous pregnancy led us to suggest sequential echography and a similar pattern of growth retardation was shown. After termination, the male fetus was found to be affected by Wiedemann-Rautenstrauch syndrome. This case shows that ultrasound examination can be a useful tool in the prenatal diagnosis of this rare, autosomal recessive syndrome. PMID- 1619644 TI - The demonstration of monozygosity in twins discordant for sacral agenesis. PMID- 1619645 TI - Proceedings of the Pathological Society of Great Britain and Ireland, 165th meeting. Manchester, July 9-10, 1992. Abstracts. PMID- 1619646 TI - Unwinding of heterologous DNA by RecA protein during the search for homologous sequences. AB - The search for homologous sequences promoted by RecA protein in vitro involves a presynaptic filament and naked duplex DNA, the multiple contacts of which produce nucleoprotein networks or coaggregates. The single-stranded DNA within the presynaptic filaments, however, is extended to an axial spacing 1.5 times that of B-form DNA. To investigate this paradoxical difference between the spacing of bases in the RecA presynaptic filament versus the target duplex DNA, we explored the effect of heterologous contacts on the conformation of DNA, and vice versa. In the presence of wheat germ topoisomerase I, RecA presynaptic filaments induced a rapid, limited reduction in the linking number of heterologous circular duplex DNA. This limited unwinding of heterologous duplex DNA, termed heterologous unwinding, was detected within 30 seconds and reached a steady state within a few minutes. Presynaptic filaments that were formed in the presence of ATP gamma S and separated from free RecA protein by gel filtration also generated a ladder of topoisomers upon incubation with relaxed duplex DNA and topoisomerase. The inhibition of heterologous contacts by 60 mM-NaCl or 5 mM-ADP resulted in a corresponding decrease in heterologous unwinding. In reciprocal fashion, the stability or number of heterologous contacts with presynaptic filaments was inversely related to the linking number of circular duplex DNA. These observations show that heterologous contacts with the presynaptic filament cause a limited unwinding of the duplex DNA, and conversely that the ability of the DNA to unwind stabilizes transient heterologous contacts. PMID- 1619648 TI - Atomic interactions in protein-carbohydrate complexes. Tryptophan residues in the periplasmic maltodextrin receptor for active transport and chemotaxis. AB - We have refined the 1.9 A resolution crystal structures of two maltodextrin receptor mutants in which tryptophan residues 230 and 232 have been changed to alanine and compared these structures with the refined 1.7 A structure of the wild-type protein. In the wild-type structure, Trp230, which is located in the maltodextrin-binding groove, stacks against the B-face of the reducing sugar of the bound maltose. Trp232, which is located near the protein surface, does not participate directly in sugar binding. Relative to the wild-type structure, neither mutation caused a significant rearrangement in the overall protein structure or in the mode of binding maltose. Although the position once occupied by Trp230 remains empty, a new water molecule has moved near the void. In contrast, a new water molecule has entered into the space once occupied by Trp232. Whereas one hydrogen bond is formed with the water molecule near the Trp230 void, no hydrogen bond is associated with the water molecule occupying the space vacated by Trp232. The three van der Waals' contacts between Trp230 and maltose in the wild-type structure that are lost in the W230A mutation could contribute to the 12-fold decrease in ligand-binding activity of the mutant protein. The W232A mutation causes little change in binding activity. The structures of these mutant proteins also provide some insight into the complicated tryptophan fluorescence spectra of the maltodextrin binding-protein. The change in fluorescence due to the deletion of Trp230 can readily be explained as resulting directly from loss of Trp230 in the sugar-binding site. The change in fluorescence due to deletion of Trp232, however, is ascribed to the modification of local interactions mediated by the binding of maltodextrin since the tryptophan is not directly involved in any sugar-binding interaction. PMID- 1619647 TI - Prediction of gene structure. AB - We have developed a hierarchical rule base system for identifying genes in DNA sequences. Atomic sites (such as initiation codons, stop codons, acceptor sites and donor sites) are identified by a number of different methods and evaluated by a set of filters and rules chosen to maximize sensitivity; these are combined into higher-order gene elements (such as exons), evaluated, filtered and combined as equivalence classes into probable genes, which are evaluated and ranked. The system has been tested on an extensive collection of vertebrate genes smaller than 15,000 bases. Results obtained show that, on average, 88% of the predicted coding region for a transcription unit is actually coding, and 80% of the actual coding is correctly predicted. This will, in most applications, be sufficient for a search against protein sequence databases for the identification of probable gene function. In addition, the system provides a general test platform for both gene atomic site identification and the rules for their evaluation and assembly. PMID- 1619649 TI - Molecular and genomic organization of clusters of repetitive DNA sequences in Caenorhabditis elegans. AB - Repetitive sequences in Caenorhabditis elegans are interspersed along the holocentric chromosomes. We have physically mapped some of these repetitive families and found that, although the distribution of members of each family is relatively even along the chromosomes, members of more than one family tend to cluster in some locations. We compared the sequence organization of 11 clusters located at known positions on different chromosomes in the N2 strain. These studies allow a comparison between repetitive elements belonging to the same family that are located on the same or on different chromosomes, providing an important tool in the study of genome turnover and evolution. PMID- 1619650 TI - Crystal structure of the factor for inversion stimulation FIS at 2.0 A resolution. AB - The factor for inversion stimulation (FIS) binds as a homodimeric molecule to a loose 15 nucleotide consensus sequence in DNA. It stimulates DNA-related processes, such as DNA inversion and excision, it activates transcription of tRNA and rRNA genes and it regulates its own synthesis. FIS crystallizes as a homodimer, with 2 x 98 amino acid residues in the asymmetric unit. The crystal structure was determined with multiple isomorphous replacement and refined to an R-factor of 19.2% against all the 12,719 X-ray data (no sigma-cutoff) extending to 2.0 A resolution. The two monomers are related by a non-crystallographic dyad axis. The structure of the dimer is modular, with the first 23 amino acid residues in molecule M1 and the first 24 in molecule M2 disordered and not "seen" in the electron density. The polypeptide folds into four alpha-helices, with alpha A, alpha A' (amino acid residues 26 to 40) and alpha B, alpha B' (49 to 69) forming the core of the FIS dimer, which is stabilized by hydrophobic forces. To the core are attached "classical" helix-turn-helix motifs, alpha C, alpha D (73 to 81 and 84 to 94) and alpha C', alpha D'. The connections linking the helices are structured by two beta-turns for alpha A/alpha B, and alpha C1 type extensions are observed at the C termini of helices alpha B, alpha C and alpha D. Helices alpha D and alpha D' contain 2 x 6 positive charges; they are separated by 24 A and can bind adjacent major grooves in B-type DNA if it is bent 90 degrees. The modular structure of FIS is also reflected by mutation experiments; mutations in the N-terminal part and alpha A interfere with FIS binding to invertases, and mutations in the helix-turn-helix motif interfere with DNA binding. PMID- 1619651 TI - Crystal structure solution and refinement of the semisynthetic cobalt-substituted bovine erythrocyte superoxide dismutase at 2.0 A resolution. AB - The semisynthetic Co-substituted bovine erythrocyte superoxide dismutase (SOD) has been crystallized in a new crystalline form and the structure determined at 2.0 A (1 A = 0.1 nm) resolution. The crystals belong to space group P2(1)2(1)2(1) with cell constants: a = 51.0, b = 147.6, c = 47.5 A, and contain one dimeric molecule of 32,000 M(r) per asymmetric unit. The structure has been solved by molecular replacement techniques using the Cu,Zn bovine enzyme as a search model, and refined by molecular dynamics with the crystallographic pseudo-energy term, followed by conventional crystallographic refinement. The R-factor for the 18,964 unique reflections in the resolution range from 10.0 to 2.0 A is 0.176 for a model comprising 2188 protein atoms and 200 solvent molecules; the root-mean square deviation from the ideal bond lengths is 0.010 A, and the average atomic temperature factor is 26.5 A2. The dimeric molecule of the enzyme is composed of two identical subunits related by a non-crystallographic 2-fold axis. The subunit has as its structural scaffolding the conventional SOD-flattened antiparallel eight-stranded beta-barrel, with three external loops. The co-ordination geometry of the metal center in the active site is fairly well preserved when compared with the native Cu,Zn bovine enzyme. Co2+ is in tetrahedral co-ordination, while the Cu2+ ligands show an uneven distortion from the square planar geometry. The least-squares superposition of the metals ligands and the catalytically important Arg141 of the native and Co-substituted enzyme yields a root-mean-square value of 0.401 A, the largest deviation occurring at the Co2+ ligand Asp81. An additional copper ligand, compatible with a water molecule, is observed at 2.38 A from Cu2+ in the active-site channel, at the supposed binding site of the O2- anion substrate. Several ordered water molecules have been observed on the protein surface and in the active-site channel; their structural locations coincide remarkably with those of related water molecules found in the crystal structure of the phylogenetically distant superoxide dismutase from yeast. PMID- 1619652 TI - A 9 A two-dimensional projected structure of cholera toxin B-subunit-GM1 complexes determined by electron crystallography. AB - Highly ordered two-dimensional crystals of cholera toxin B-subunit pentamers have been grown by specific interaction with planar lipid films containing monosialoganglioside GM1. Electron diffractograms of frozen-hydrated crystals show diffraction peaks extending to beyond 4 A, while electron images diffract to 8 A. A two-dimensional projected structure of cholera toxin B-subunit-GM1 complex has been calculated at 9 A resolution by combining electron diffraction and image data. Crystals present an approximate pgg projection symmetry, with unit cell dimensions a = 119(+/- 1) A, b = 123(+/- 1) A, gamma = 90 degrees. Each pentameric assembly presents two concentric rings of electron scattering density, separated by an area of lower density. The outer and inner rings are centered at 25 A and and 11 A from the pentamer centre, respectively. The apparent projected density of the outer ring is larger than that of the inner ring. We propose that the outer and inner density rings correspond respectively to the peripheral beta sheet arrangement and the central alpha-helix barrel, recently identified in the crystal structure of the heat-labile enterotoxin from Escherichia coli. PMID- 1619653 TI - A 500 ps molecular dynamics simulation study of interleukin-1 beta in water. Correlation with nuclear magnetic resonance spectroscopy and crystallography. AB - We report the results of a 500 ps molecular dynamics simulation of the cytokine interleukin-1 beta, a protein of 153 amino acids, immersed in a sphere of 3783 bulk water molecules with a radius of 33 A. The simulation reproduces the amplitudes of the fast librational motions of the backbone N-H bonds determined from 15N nuclear magnetic relaxation data, as well as the crystallographic B factors. Moreover, this study suggests a molecular picture of the nature of the slow internal motions that have been inferred from nuclear magnetic resonance relaxation experiments. These experiments indicated that, in addition to fast motions common to all residues, 32 surface residues exhibit slow motions on the 400 ps to 5 ns time-scale. While the present simulation is not sufficiently long to provide a quantitative description of events on this time-scale, it is long enough to observe several large amplitude transitions that are likely candidates for these slow motions. Specifically, in many of these 32 residues, the N-H groups are hydrogen bonded and infrequent dihedral transitions cause the N-H vectors to jump between states with well-defined orientations. It is shown that the time course of the angular reorientational correlation functions of these residues calculated from the trajectory is a reflection of the random times at which these infrequent jumps happen to have occurred. Thus, while the rate of these transitions cannot be quantified, the simulated decay of these correlation functions is completely consistent with the physical picture in which the N-H vectors, in addition to fast librational motion, undergo large amplitude jumps between conformations stabilized by hydrogen bonds. PMID- 1619654 TI - Towards an understanding of the arginine-aspartate interaction. AB - We have made a comparison of the geometries of intra- and intermolecular arginine aspartate interactions by extracting orientation information from protein co ordinate data. The results show a pronounced difference, with both types of interaction preferring to form twin N-H . . . O = C hydrogen bonds, but involving different nitrogen atoms. In intramolecular interactions, the aspartate favours a "side on" geometry, forming hydrogen bonds with N epsilon and N eta 2; in the intermolecular case, however, "end on" contacts involving N eta 1 and N eta 2 of the arginine are preferred. We have used Distributed Multipole Analysis of the methylguanidinium-acetate system to model the electrostatic component of the arginine-aspartate ion pair interaction in vacuo. We find, in agreement with the experimental arginine-aspartate distribution, that side on and end on doubly N-H . . . O = C hydrogen-bonded configurations are clearly the most favourable, with the side on being marginally lower in energy. Thus, despite the many competing side-chain interactions in proteins, many arginine-aspartate pairs adopt one of the minimum electrostatic energy conformations, or one close to a minimum. Within each of the two regions (side on and end on) we find only a small energy gap between the "symmetric" doubly hydrogen-bonded and slightly displaced "staggered" structures, again in agreement with the crystal structure data. Further calculations of the total ab initio interaction energy show that this follows the electrostatic term in its orientational variation, this phenomenon of "electrostatic domination" being well known in hydrogen-bonded systems. The end on arginine nitrogen atoms are observed to be more surface-exposed than N epsilon, as demonstrated by their greater accessibilities over a large sample of proteins. This helps explain the side on and end on preferences of intra- and intermolecular interactions, respectively. We also note the effect of short sequence intervals, particularly i in equilibrium with i + 2 relationships, in forcing many intramolecular contacts to be side on. PMID- 1619655 TI - Modulation of thrombin-hirudin interaction by specific ion effects. AB - Kinetic studies of the inhibition of thrombin amidase activity by recombinant hirudin have been conducted as a function of salt concentration in the range 0.05 to 1 M, using NaCl, KCl, NaBr and KBr. At the same ionic strength, the value of KI for thrombin-hirudin interaction is found to be different with different salts. The slope d ln KI/d ln a+/-, where a+/- is the mean ion activity, is constant in the range 0.05 to 0.5 M, is sensitive to the particular salt present in solution and is equal to 1.07 +/- 0.09 (NaCl), 0.92 +/- 0.10 (KCl), 1.37 +/- 0.10 (NaBr) and 0.56 +/- 0.10 (KBr). These results indicate that specific ion effects are involved in the modulation of thrombin-hirudin interaction in the form of ion release, as recently found in the case of thrombin interaction with its natural substrate fibrinogen. The linkage hierarchy for ion release found in the case of thrombin-fibrinogen interaction also applies in the case of thrombin hirudin interaction, with the number of released ions decreasing in the order NaBr greater than NaCl greater than KCl greater than KBr. It is proposed that the process of bridge-binding to the fibrinogen recognition site and the catalytic pocket of the enzyme, as seen in the case of fibrinogen and hirudin, is linked to ion release and controlled by modulation of the association rate constant. PMID- 1619656 TI - Crystallization and preliminary X-ray study of minor glucoamylase from Aspergillus awamori variant X-100/D27. AB - Crystals of the reduced form of glucoamylase were obtained from polyethylene glycol 6000 solution by the hanging-drop method. The protein was treated with alpha-mannosidase to partly remove the sugar component. The crystals belong to the space group P2(1)2(1)2(1) with cell dimensions a = 116.7 A, b = 104.3 A, c = 48.5 A and diffract beyond 2.5 A resolution. PMID- 1619657 TI - Crystallization, activity assay and preliminary X-ray diffraction analysis of the uncleaved form of the serpin antichymotrypsin. AB - Crystals of recombinant wild-type antichymotrypsin have been prepared by the method of vapor diffusion with polyethylene glycol 4000 as a precipitant at pH 5.7. Two crystal forms are observed. One form belongs to tetragonal space group P4(3)2(1)2 (or P4(1)2(1)2) and has unit cell dimensions a = b = 126 A, c = 243 A, with two molecules in the asymmetric unit. The other crystal form belongs to orthorhombic space group P2(1)2(1)2(1) and has unit cell parameters of a = 73 A, b = 78 A and c = 80 A, with one molecular in the asymmetric unit. Diffraction intensity measurements have been made on the tetragonal crystal form to a limiting resolution of 4.1 A, and reflections have been observed on X-ray still photographs to a limiting resolution of 2.5 A for the orthorhombic form. An activity assay of redissolved tetragonal form crystals indicates that the uncleaved, functional serpin has been crystallized. PMID- 1619658 TI - Crystallization of Sindbis virus and its nucleocapsid. AB - Crystals of Sindbis virus, which contains a lipid-bilayer membrane, have been grown using polyethylene glycol. The space group is R32, a = b = 640 A, c = 1520 A. The crystals are highly mosaic, and recorded diffraction is therefore restricted to spacings of about 30 A. The crystals show that the packing of glycoproteins E1 and E2 in the icosahedral outer shell is sufficiently precise that it permits regular and repeated interactions between virus particles in the lattice. Crystals of Sindbis nucleocapsids have also been grown. The limited diffraction data are consistent with close packing of nucleocapsids 404 A in diameter. PMID- 1619659 TI - Crystallization and preliminary X-ray crystallographic analysis of Mirabilis antiviral protein. AB - Mirabilis antiviral protein is a single-chain ribosome-inactivating protein purified from the tuberous root of Mirabilis jalapa L. We obtained several forms of crystals of the protein by the hanging drop vapor diffusion method, but most of these crystals were not suitable for X-ray crystallography. After refining the growth conditions, crystals of crystallographic quality were grown in 20 microliters droplets of an equi-volume mixture of 1.5% (w/v) protein solution and a reservoir solution containing 49 to 50% (w/v) ammonium sulfate and 50 mM ammonium citrate (pH 5.4) at room temperature. Addition of 2 mM-adenine sulfate reduced twinning and "crystal shower". The resulting trigonal crystals diffract beyond 2.5 A resolution using a rotating anode X-ray generator. The space group was determined to be P3(1)21 or P3(2)21 (a = b = 103.9.A, c = 134.6 A, alpha = beta = 90 degrees, gamma = 120 degrees) based on their precession photography of h0l and hk0 zones. There seems to be three monomers in an asymmetric unit for VM = 2.51 A3/Da. PMID- 1619660 TI - Contribution of the hydrophobic effect to globular protein stability. AB - The decrease in conformational stability, delta(delta G), has been measured for 72 aliphatic side-chain mutants from four proteins in which a larger side-chain is replaced by a smaller side-chain so that steric effects are minimal. When these delta(delta G) values are corrected to the same accessibility, namely 100% buried, then the following -delta(delta G) values per -CH2- group (in kcal/mol) are obtained: Ile----Val (1.26), Ala (1.26), Gly (1.26); Leu----Ala (1.16), Gly (1.21); Val----Ala (1.23), Gly (1.53). The average of these values is 1.27(+/- 0.07) kcal/mol. The 72 individual values range from 0 to 2.4 kcal/mol with an average value of 1.27(+/- 0.51) (standard deviation) kcal/mol. When the delta Gtr values from n-octanol to water are corrected for the difference in volume between the solutes and the solvents, the average value for the same substitutions is 1.25(+/- 0.05) kcal/mol. This suggests that proteins gain 1.3(+/- 0.5) kcal/mol in stability for each -CH2- group buried in folding, and, furthermore, that the volume corrected delta Gtr values for n-octanol for the amino acid side-chains provide good estimates of the contribution of the hydrophobic effect to globular protein stability. PMID- 1619661 TI - Asp537, Asp812 are essential and Lys631, His811 are catalytically significant in bacteriophage T7 RNA polymerase activity. AB - To define catalytically essential residues of bacteriophage T7 RNA polymerase, we have generated five mutants of the polymerase, D537N, K631M, Y639F, H811Q and D812N, by site-directed mutagenesis and purified them to homogeneity. The choice of specific amino acids for mutagenesis was based upon photoaffinity-labeling studies with 8-azido-ATP and homology comparisons with the Klenow fragment and other DNA/RNA polymerases. Secondary structural analysis by circular dichroism indicates that the protein folding is intact in these mutants. The mutants D537N and D812N are totally inactive. The mutant K631M has 1% activity, confined to short oligonucleotide synthesis. The mutant H811Q has 25% activity for synthesis of both short and long oligonucleotides. The mutant Y639F retains full enzymatic activity although individual kinetic parameters are somewhat different. Kinetic parameters, (kcat)app and (Km)app for the nucleotides, reveal that the mutation of Lys to Met has a much more drastic effect on (kcat)app than on (Km)app, indicating the involvement of K631 primarily in phosphodiester bond formation. The mutation of His to Gln has effects on both (kcat)app and (Km)app; namely, three- to fivefold reduction in (kcat)app and two- to threefold increase in (Km)app, implying that His811 may be involved in both nucleotide binding and phosphodiester bond formation. The ability of the mutant T7 RNA polymerases to bind template has not been greatly impaired. We have shown that amino acids D537 and D812 are essential, that amino acids K631 and H811 play significant roles in catalysis, and that the active site of T7 RNA polymerase is composed of different regions of the polypeptide chain. Possible roles for these catalytically significant residues in the polymerase mechanism are discussed. PMID- 1619662 TI - Formation of open and elongating transcription complexes by RNA polymerase III. AB - The Saccharomyces cerevisiae transcription factors (TF) IIIB and IIIC assemble onto their respective DNA-binding sites on the SUP4 tRNA(Tyr) gene at 0 degrees C. RNA polymerase III specifically associates at 0 degrees C with this TFIIIC TFIIIB-DNA complex to form a stable "closed" promoter complex in which the DNA surrounding the transcriptional start retains its duplex form. Promoter "opening" is a temperature-dependent and readily reversible process that involves up to 22 unwound base-pairs of DNA, and can be followed by analyzing the hyperreactivity of thymine to KMnO4 oxidation. This promoter opening increases progressively from 10 degrees C to 40 degrees C, with at least two regions within the transcription bubble appearing to melt independently. In contrast, the temperature dependence of forming an initiated transcription complex containing a 17 nucleotide nascent RNA chain displays a sharp transition between 10 degrees C and 15 degrees C. When RNA polymerase initiates transcription under conditions that limit the nascent RNA chain to less than six nucleotides, there is no displacement of the transcription bubble. These transcription complexes are distinguishable from "open" promoter complexes in their maintenance of the transcription bubble at 0 degrees C, and from transcription complexes with more extended (17 nucleotide) RNA chains in their sensitivity to disruption by heparin. In light of recent results by others that demonstrate a requirement for an RNA transcription factor in a Bombyx mori-based in vitro RNA polymerase III transcription system, we have searched for a comparable component in the S. cerevisiae-derived system. We show that if an RNA component is required in the yeast-derived system, it is not susceptible to inactivation by massive amounts of micrococcal nuclease, RNase A, or RNase T1. PMID- 1619663 TI - Isorepressor of the gal regulon in Escherichia coli. AB - Inducible overexpression of the Escherichia coli gal operon in the absence of the Gal repressor is known as ultrainduction. The requirement of induction can be eliminated by mutation of a new locus, galS, resulting in constitutive and ultrainduced levels of gal expression. Characterization of the galS gene and its product has revealed an isorepressor of the gal regulon. The Gal isorepressor is a protein of 346 amino acid residues whose amino acid sequence and cellular function, as described here, are very similar to that of Gal repressor, encoded by the galR gene. Transcription from different promoters of the gal regulon, galP1, galP2 and mglP, was examined by primer extension and reverse transcription of mRNA isolated from strains containing mutations in galR and/or galS. In strains containing a galS mutation, overexpression of gal message occurred only in the presence of inducer, while mgl message was constitutively derepressed. The galS mutation also constitutively derepressed an mglA::lacZ fusion, demonstrating that GalS is the mgl repressor. A potential operator site in the mgl promoter was identified at a position analogous to OE in gal. Thus, the gal and mgl operons constitute a regulon. Crosstalk, temporal action, induction spectrum or heteromer formation between repressor and isorepressor may help co-ordinate high affinity galactose transport and galactose utilization. PMID- 1619664 TI - Molecular interactions in myosin assembly. Role of the 28-residue charge repeat in the rod. AB - We have used internal deletions of multiples of seven residues to change the phase of the 28-residue charge repeat in a light meromyosin cDNA construct expressed in Escherichia coli. The solubility behaviour of these mutants was similar to that of the wild-type material, but the molecular packing in the aggregates formed at low ionic strength was different. Whereas wild-type material formed paracrystals in which molecules were in close contact over most of their length, molecules in the paracrystals formed by the mutants were in close contact for only a short distance, which was just short enough to exclude the deletion from the overlap. These data indicate that, although the 28-residue charge periodicity is important in myosin molecular interactions, it is probably not the major driving force for myosin assembly and instead influences the detailed axial stagger of the interacting molecules. PMID- 1619665 TI - Mutagenesis of the Bacillus subtilis "-12, -24" promoter of the levanase operon and evidence for the existence of an upstream activating sequence. AB - The levanase operon of Bacillus subtilis is controlled by RNA polymerase associated with sigma 54 factor and by the LevR activator that is homologous to the NifA/NtrC family of regulators. A "-12, -24" promoter is present at the appropriate distance from the transcription start site. The drastic down effect of base substitutions in the TGGCAC, TTGCA consensus sequence on the expression of the levanase operon confirmed the involvement of the "-12, -24" region in promoter function. Deletion derivatives of the upstream sequence of the operon promoter were constructed using translational levD'-'lacZ fusions and were integrated as single copies at the amyE locus of the B. subtilis chromosome. A cis-acting DNA sequence that is required for activation of the operon promoter by LevR was identified. This regulatory sequence is about 50 base-pairs long and is centered 125 base-pairs upstream from the transcription start site in a region containing a 16 base-pair palindromic structure. This region of dyad symmetry functions as a regulatory element when placed up to at least 600 base-pairs upstream from the "-12, -24" promoter, although the efficacy of activation is lowered. Thus, in common with most sigma 54-dependent promoters, an upstream activating sequence (UAS) is involved in the control of expression of the levanase operon. The isolation and characterization of eight mutations in the UAS region confirmed the importance of the palindromic structure in promoter activation. Moreover, the expression of the levanase operon was inhibited by placing the UAS in trans on a multicopy plasmid, probably through titration of the LevR polypeptide. In conclusion, the levanase promoter region can be divided into two regulatory sequences: the "-12, -24" promoter recognized by the sigma 54 RNA polymerase holoenzyme and the UAS, an inverted repeat sequence that is probably the LevR binding site. PMID- 1619666 TI - Interstitial adenosine: the measurement, the interpretation. PMID- 1619667 TI - Heterogeneity and sampling volume dependence of epicardial adenosine concentrations. AB - Rapid steady-state estimates of interstitial fluid (ISF) adenosine concentrations (ADOi) in the left ventricular epicardium of anesthetized dogs were obtained by the epicardial porous disc (EPD) method described herein. Because of the high temporal and spatial resolution of this method, it was ideally suited to test the hypothesis that ADOi may vary in these domains. Variance in steady-state EPD solute concentrations was quantified statistically by the coefficient of variation (CV = standard deviation/mean), which we used as an index of heterogeneity. A significant temporal variation in steady-state EPD adenosine concentrations was observed when samples were sequentially collected from one epicardial location (CV = 42.9 +/- 3.5%). When steady-state sample pairs (n = 45) were collected simultaneously from two distinct epicardial locations, a 2.6 +/- 0.3-fold mean difference in their respective adenosine concentrations was measured. About 25% of this variation was inherent in procedural methodology, based on the variability of steady-state EPD concentrations of extracellularly equilibrated 14C sucrose (CV = 12.7 +/- 1.2%) and the variability of steady-state concentrations of both solutes measured using in vitro preparations (mean CV = 9.7 +/- 1.2%). Thus, we contend that endogenous myocardial ISF adenosine is temporally and perhaps spatially heterogeneous. Our estimates of steady-state ADOi obtained with the EPD method ranged from 0.47 to 0.99 microM. Using modifications of the EPD technique and the epicardial chamber, we also demonstrated that the adenosine concentration in 'steady-state' epicardial samples is reduced when the volume/surface area ratio of the sample buffer is increased. We hypothesize that sampling-induced decreases in steady-state ADOi underlie these observations, because losses of ISF adenosine to high volumes of sample buffer can be greater than the myocardial cells are capable of replacing. However, with the very low volume/surface area ratio of a single EPD (7.5 microliters/cm2), steady-state ADOi may remain constant during sampling, allowing for accurate determinations of ADOi with this method. PMID- 1619668 TI - Protective activity of the spin trap tert-butyl-alpha-phenyl nitrone (PBN) in reperfused rat heart. AB - The aim of this work was to ascertain whether free radicals play a causal role in the injury occurring in myocardial ischemia and reperfusion. To this purpose we observed whether spin-trapping compounds protect the heart when used at a concentration capable of reacting with free radicals. The lipophilic spin trap alpha-phenyl-t-butyl nitrone (PBN) was used because it is taken up by the myocites. Isolated Langendorff rat hearts were subjected to ischemia according to two schemes: "Model A" = 30 min zero-flow ischemia followed by 30 min reperfusion; "Model B" = 60 min of low-flow ischemia (10% of the individual value; N2 saturated) followed by 30 min reperfusion. Treated groups received in addition 5.0 mM PBN which was supplied continuously. The following parameters were measured throughout the experiment: contractile performance (RPP); coronary flow (CF); CPK; phosphocreatine (PCr), ATP, inorganic phosphate (Pi), intracellular pH (pHi). The pathology obtained by "Model A" is more severe than that of Model B, and partly irreversible. During the ischemic phase in "Model A", contractility, PCr and ATP dropped to near zero; during initial reflow CPK rose about 13-fold and Pi rose 2.5-fold, while pHi decreased to 6.1. During reperfusion, a partial recovery of PCr, Pi and pHi was observed, while RPP and ATP did not increase; PBN treatment improved significantly PCr and CPK, while the other parameters were unaffected. During ischemia, "Model B" hearts showed a drop of contractility to near zero, of PCr to 35%, of ATP to 50%; CPK rose 7-fold and Pi 1.5-fold; pHi was not modified. During reperfusion, all parameters recovered in part, with exception of Pi. PBN developed a marked protective activity on all tested parameters, which gained a nearly normal value. The results of the present investigations show that the lipophilic spin trap PBN partly protects the heart from the ischemia/reperfusion injury, thus confirming that free radicals play a causal role in this pathology; the continuous loading of the tissue with the drug can be an important factor for obtaining the protective effect. PMID- 1619669 TI - Myocardial glycoproteins in diabetes: type VI collagen is a major PAS-reactive extracellular matrix protein. AB - An investigation of myocardial glycoproteins was undertaken to elucidate the molecules responsible for the periodic acid-Schiff (PAS) reactivity of the increased extracellular matrix of diabetic cardiomyopathy. Perfusion with radiolabeled mannose indicated an enhanced formation of matrix components in the diabetic compared to the normal rat heart. Electrophoretic separation of radiolabeled extracts demonstrated the presence of glycoproteins with Mr values of 205, 142 and 90 kDa which could be separated by Bio-Gel A-5 m filtration. Fractionation of non-perfused hearts resulted in the isolation of only the 205 and 142 kDa components, which were shown by amino acid analyses and collagenase digestion to belong to the collagen family of proteins and by immunoblotting to represent type VI collagen. The carbohydrate content of these rat myocardial type VI collagen subunits, determined from monosaccharide analyses, was 11 and 12%, respectively, and N-glycanase digestion of the 142 kDa chain resulted in a decrease in size of approximately 14 kDa, indicating the presence of asparagine linked units. Examination of normal and diabetic rat heart sections indicated that the latter contained abundant PAS-positive strands and nodules which corresponded to the distribution of anti type VI collagen reactivity. Moreover, immunoblots showed higher levels of Type VI collagen in diabetic than in normal heart extracts. Type VI collagen therefore appears to represent a major glycoprotein of myocardial extracellular matrix and to be implicated in diabetic cardiomyopathy. PMID- 1619670 TI - Diabetes and susceptibility to reperfusion-induced ventricular arrhythmias. AB - Studies using chemically-induced models of diabetes have shown the diabetic myocardium to exhibit abnormalities in cellular ion transport, which may affect susceptibility to reperfusion-induced arrhythmias. We studied the incidence of reperfusion-induced ventricular tachycardia (VT) and fibrillation (VF) in isolated hearts from rats with streptozotocin-induced diabetes and from age matched and weight-matched control rats (n = 12 per group). Following 5 min of regional ischaemia, reperfusion resulted in a similarly low incidence of arrhythmias in all three groups. Following 10 min of regional ischaemia, the incidence of VT was 92, 100 and 92%, and the incidence of VF was 75, 92 and 92% in diabetic, age-matched control and weight-matched control groups, respectively (NS). However, among those hearts which exhibited VF, the incidence of sustained (greater than or equal to 120 s) VF was 73 and 55% in age-matched and weight matched control groups, respectively, and 0% in the diabetic group (P less than 0.05 vs both controls). The mean duration of VF in the diabetic group was reduced from 201 +/- 33 and 171 +/- 36 s in age-matched and weight-matched control groups, respectively, to 9 +/- 3 s (P less than 0.05). Thus, streptozotocin induced diabetes in the rat does not result in an increased susceptibility to reperfusion-induced arrhythmias. To the contrary, hearts from diabetic rats are less susceptible to potentially lethal arrhythmias during reperfusion. Likely contributory factors to this phenomenon include (i) increased myocardial content of free radical scavenging enzymes, (ii) prolonged action potential duration, and (iii) reduced activity of sarcolemmal Na+/H+ and Na+/Ca2+ exchange processes, all of which have previously been reported in similar models of diabetes. PMID- 1619671 TI - Cytosolic Ca2+ concentration and pH of diabetic rat myocytes during metabolic inhibition. AB - To investigate the role of Ca2+ metabolism and pH in diabetic cardiomyopathy, intracellular Ca2+ concentration ([Ca2+]i) and intracellular pH (pHi) of isolated myocytes were measured simultaneously using fura-2 and BCECF. We used diabetic (D.M.) rats at 8 weeks after the injection of streptozotocin (45 mg/kg, i.v.). (1) [Ca2+]i of D.M. myocytes was lower than that of controls (53 +/- 3 and 75 +/- 5 nM, mean +/- S.E., P less than 0.01). There was no difference in pHi (7.06 +/- 0.02 in D. M., 7.07 +/- 0.02 in control). There was no difference in the percentage of non-rounded cells at 30 min after the perfusion of glucose-free solution which contained 2 mM sodium cyanide (NaCN) between D.M. and controls (53% and 52%). When cells were rounded, the value of [Ca2+]i was significantly lower in D.M. myocytes than that in controls (172 +/- 21 and 421 +/- 106 nM, P less than 0.05). (2) When the cells were shortened or rounded in the high [Ca2+]o solution (24.5 mM), [Ca2+]i of D.M. rats was significantly lower than that of control rats. (3) The percentage of non-rounded cells at 30 min after the perfusion of NaCN increased in controls by 50 mM glucose (95%, P less than 0.01), but not in D.M. (47%). Insulin (25 mU/ml) and glucose (15 mM) increased the percentage of non-rounded cells in D.M. after 30 min perfusion with NaCN (88%, P less than 0.01 v.s. 53% without glucose nor insulin). It is suggested that there are disturbances of Ca2+ metabolism in D.M. myocytes, and that there is a close relation between cell injury and glucose utilization during metabolic inhibition. PMID- 1619673 TI - Breakdown of the blood-brain barrier after fluid percussive brain injury in the rat. Part 1: Distribution and time course of protein extravasation. AB - Experimental brain injury is associated with marked vasogenic edema, as evidenced by an increase in brain water content. This prominent and widespread response raises questions about the vulnerability of microvasculature in the brain to injury. In the present report we further characterize the vascular response by evaluating the integrity of the blood-brain barrier to circulating proteins. Vascular permeability to endogenous immunoglobulins (IgG) and to the protein horseradish peroxidase (HRP) was examined after a lateral, fluid percussive brain injury in the rat. In study 1 IgG was immunolocalized in brain sections 1-24 hr after injury. In studies 2 and 3 HRP was given intravenously either before impact (study 2) or 10 min before sacrifice (study 3). Permeability to this protein was assessed at 1-6 hr (study 2) or at 1-72 hr (study 3) after injury. In studies 1 and 2 the extravascular accumulation of proteins was evaluated. Pronounced abnormal permeability to IgG and HRP occurred within the first hour after injury and was widespread throughout both hemispheres. The intensity of immunostaining for IgG increased with time up to 24 hr after injury. In contrast, maximal extravascular accumulation of HRP occurred within the first hour after injury. In study 3 the time course for re-establishment of the blood-brain barrier to HRP was determined. Maximal permeability occurred at 1 hr after injury. At 24 hr abnormal permeability was restricted to the impact site and this area remained permeable up to 72 hr after injury. In summary this study demonstrates that breakdown of the blood-brain barrier to plasma proteins is a prominent feature of experimental brain injury. This abnormal permeability is characterized by its transient expression and widespread distribution. The time course for re establishment of the blood-brain barrier to circulating proteins is most delayed at the impact site. PMID- 1619672 TI - Cognitive deficits following traumatic brain injury produced by controlled cortical impact. AB - Traumatic brain injury produces significant cognitive deficits in humans. This experiment used a controlled cortical impact model of experimental brain injury to examine the effects of brain injury on spatial learning and memory using the Morris water maze task. Rats (n = 8) were injured at a moderate level of cortical impact injury (6 m/sec, 1.5-2.0 mm deformation). Eight additional rats served as a sham-injured control group. Morris water maze performance was assessed on days 11-15 and 30-34 following injury. Results revealed that brain-injured rats exhibited significant deficits (p less than 0.05) in maze performance at both testing intervals. Since the Morris water maze task is particularly sensitive to hippocampal dysfunction, the results of the present experiment support the hypothesis that the hippocampus is preferentially vulnerable to damage following traumatic brain injury. These results demonstrate that controlled cortical impact brain injury produces enduring cognitive deficits analogous to those observed after human brain injury. PMID- 1619674 TI - The novel 21-aminosteroid U74006F attenuates cerebral edema and improves survival after brain injury in the rat. AB - The present study evaluated the effect of the nonglucocorticoid 21-aminosteroid U74006F, an inhibitor of iron-dependent lipid peroxidation, on the development of regional cerebral edema after lateral fluid-percussion (FP) brain injury. Male Sprague-Dawley rats (n = 40) were anesthetized and subjected to FP brain injury of moderate severity centered over the left parietal cortex (2.5-2.6 atms). Fifteen minutes after brain injury, animals randomly received an i.v. bolus of either U74006F (3 mg/kg, n = 21) followed by a second bolus (3 mg/kg) at 3 hr or buffered sodium citrate vehicle (equal volume, n = 15). An additional group of 12 surgically prepared but uninjured animals served as preinjury controls. At 48 hr after injury, animals were sacrificed and brain tissue assayed for water content and regional cation concentrations. With the use of specific gravimetric techniques, no significant differences were observed in posttraumatic cerebral edema between drug- and control-treated animals. However, using wet weight/dry weight methodology, we found that administration of U74006F significantly reduced water content in the right hippocampus (contralateral to the site of injury) compared to saline-treated animals (p less than 0.05). U74006F also significantly prevented the postinjury increase in sodium concentrations in the ipsilateral hippocampus (p less than 0.05) and thalamus (p less than 0.03). Regional concentrations of potassium were unaltered after drug treatment. Administration of U74006F significantly reduced postinjury mortality, from 28% in control animals to zero in treated animals (p = 0.01). These results suggest that lipid peroxidation may be involved in the pathophysiological sequelae of brain injury and that 21-aminosteroids may be beneficial in the treatment of brain injury. PMID- 1619675 TI - Tumor-specific T-cell immunity: ready for prime time? PMID- 1619676 TI - Oregon health system overhaul may become national model. PMID- 1619677 TI - Unconventional methods under review by NIH. PMID- 1619678 TI - Researchers link low literacy to high health care costs. PMID- 1619679 TI - Far East's cancer mortality patterns shift, reflecting cultural changes. PMID- 1619680 TI - ACS mobilizes forces to keep record straight. PMID- 1619681 TI - NCI appropriations law not expected until fall. PMID- 1619682 TI - Antitumor activity and immune responses induced by a recombinant carcinoembryonic antigen-vaccinia virus vaccine. AB - BACKGROUND: Human carcinoembryonic antigen (CEA) is a 180-kd glycoprotein expressed in human colorectal, gastric, pancreatic, breast, and non-small-cell lung carcinomas. Previous studies have demonstrated enhanced immune responses to other antigens presented with vaccinia virus proteins via a recombinant vaccinia virus construct. In addition, we have developed a recombinant CEA-vaccinia virus construct, designated rV(WR)-CEA, and have demonstrated humoral anti-CEA responses in mice after immunization with that virus. PURPOSE: The goals of this study were (a) to construct a recombinant CEA-vaccinia vaccine in a less virulent vaccinia strain that is potentially safe and effective for treatment of patients whose tumors express CEA and (b) to evaluate the ability of the recombinant CEA vaccinia vaccine to prevent and reverse tumor growth in mice and to elicit cell mediated and humoral anti-CEA immune responses. METHODS: Using the New York City strain of vaccinia virus, which is used in smallpox vaccination and is more attenuated for humans than rV(WR), we derived a recombinant CEA-vaccinia construct, designated rV(NYC)-CEA. The ability of this construct to induce antitumor immunity was evaluated in mice receiving subcutaneous injections of murine colon adenocarcinoma cells expressing the human CEA gene. RESULTS: Administration of rV(NYC)-CEA in mice induced strong anti-CEA antibody responses, as well as CEA-specific cell-mediated responses, including delayed-type hypersensitivity, lymphoproliferative, and cytotoxic responses. Vaccination of mice with the rV(NYC)-CEA rendered them resistant to the growth of subsequently transplanted CEA-expressing tumors. Moreover, when mice were vaccinated 7 days after tumor cell injection, tumor growth was either greatly reduced or eliminated. No toxic effects were observed in any of the mice. CONCLUSION: These studies demonstrate that antitumor activity can be induced with the use of a recombinant CEA-vaccinia virus construct derived from an attenuated vaccinia strain, and they reveal the range of cell-mediated and humoral responses induced by this recombinant vaccine. PMID- 1619683 TI - Dietary fat and postmenopausal breast cancer. AB - BACKGROUND: Although the results of animal studies and cross-cultural comparisons generally support a role for dietary fat in the etiology of breast cancer, results of analytic epidemiology studies are equivocal. PURPOSE: The association between dietary fat and subsequent breast cancer was examined in a cohort of 34,388 postmenopausal women from Iowa. METHODS: Dietary habits were assessed by a food-frequency questionnaire mailed in January 1986. Through December 31, 1989, 459 incident cases of breast cancer occurred in this cohort. Proportional hazards regression was used to examine the dietary fat-breast cancer association while adjusting for potential confounders. The effects on this association of four analytic approaches to adjustment for energy intake were also considered. RESULTS: After adjustment for known determinants of breast cancer, a modest positive association of total fat intake with risk of breast cancer was seen. Polyunsaturated fat intake was also positively associated with breast cancer (relative risk from lowest to highest intake, 1.0, 1.25, 1.31, and 1.49; P for trend = .052). Different approaches to adjustment for energy intake, however, provided different impressions of the dietary fat-breast cancer association. One method, involving categorization of crude fat intake and inclusion of total energy intake in regression analysis, gave relative risk estimates from low to high fat intake of 1.0, 1.17, 1.25, and 1.38 (P for trend = .18). Another method, based on categorization of fat intake residuals in which the variation in fat due to total energy intake was removed, gave corresponding estimates of 1.0, 1.24, 1.30, and 1.16 (P for trend = .29). The former suggests increasing breast cancer risk with increasing fat intake; the latter suggests no association. CONCLUSIONS: These results are consistent with other cohort studies that have shown a weak association or no association between dietary fat and breast cancer. They are also consistent with studies suggesting that fat intake is a determinant of breast cancer, particularly after accounting for inaccuracies in dietary assessment. The effects of different energy-adjustment methods may account in part for the varying interpretations of four previous cohort studies of dietary fat and breast cancer. IMPLICATIONS: Further work is needed to clarify not only the nature of the dietary fat-breast cancer association, but also the impact of different analytic methods used in the investigation of diet-disease associations. PMID- 1619684 TI - Molecular genetic studies of tumor suppressor gene regions on chromosomes 13 and 17 in colorectal tumors. AB - BACKGROUND: In the majority of colorectal carcinomas, both copies of the tumor suppressor gene TP53 (tumor protein 53) are known to be inactivated. In contrast to a loss of tumor suppressor function, it has been suggested that an increased copy number of the RB1 gene is involved in the progression of these tumors. PURPOSE: To determine genetic alterations at chromosomes 13 and 17 in colorectal tumors, we have studied several loci on these chromosomes, with special focus on the RB1 and TP53 genes at both the level of DNA sequence and the level of gene expression. METHODS: Restriction fragment length polymorphism analysis was performed after alkaline Southern blotting of the DNA fragments and hybridization (in 7% sodium dodecyl sulfate and 0.5 M NaPO4) of the nylon membranes with multiprimed, radioactively labeled probes. Total RNA was extracted from tissue biopsy specimens by homogenization of the samples in guanidinium thiocyanate followed by separation in a CsCl gradient. By use of an image-processing system, x-ray film signals were measured densitometrically. Point mutations within the TP53 gene were detected by use of polymerase chain reaction (PCR) in combination with constant denaturant gel electrophoresis. Direct sequencing of PCR products revealed the exact nature of the mutations. Protein expression of TP53 was seen by immunostaining of sections from paraffin-embedded material using a mouse monoclonal antibody. The two-sided Fisher's Exact Test was used for statistical analysis. RESULTS: An increase in allelic copy number at 13q loci was seen in 10 (32%) of 31 tumors. In the majority of the cases, this increase probably reflected a change in the diploid status of chromosome 13; in some cases, however, only part of the 13q seemed to be involved. The RB1 gene showed an elevated level of RNA compared with the beta-actin signal. Fourteen (48%) of 29 tumors showed loss of heterozygosity at loci on 17p, and base mutations within the TP53 gene were seen in 14 (42%) of 33 tumors. RNA and protein analyses of TP53 revealed an increased level of expression in the tumors compared with normal mucosa. Allelic variations seen at 13q and 17p were not associated (P = .7). CONCLUSIONS: Our results suggest that, in addition to aneuploidy, gain of specific chromosome 13 sequences is involved in the tumorigenesis of the colon and rectum. In addition, they confirm the importance of TP53 mutations for the progression of such tumors and support the view that accumulation of events is more important than the order of events. The genetic changes observed at chromosome arms 13q and 17p seem to be independent of each other. PMID- 1619685 TI - Breast cancer risks in relatives of male breast cancer patients. AB - BACKGROUND: Previous studies have provided conflicting results concerning the familial effect of male breast cancer on breast cancer risks in female relatives. PURPOSE: We studied breast cancer risks in first-degree relatives of male patients and compared them with relatives of female patients. METHODS: Our study included 88 consecutively ascertained male patients and 320 of their first-degree relatives as well as 186 consecutively ascertained female patients and 633 of their first-degree relatives. Observed numbers of breast cancers in relatives were compared with the expected number derived from the Connecticut Tumor Registry. Multiple logistic regression analysis was also performed. RESULTS: Relatives of male patients exhibited a significant twofold increased risk when compared with expected rates and no difference in risk when compared with that of relatives of female patients. Prostate cancer in the family of a male patient resulted in a significant fourfold increased breast cancer risk compared with a risk of 1.4 in families with no history of prostate cancer. A family history of lung cancer, colon cancer, or melanoma had no effect on increasing risks of breast cancer. CONCLUSION: The familial effect of male breast cancer is the same as that of female breast cancer. IMPLICATIONS: Any estimates of breast cancer risk provided to individuals should also consider the occurrence of prostate cancer in the family, since prostate cancer appears capable of at least doubling the underlying twofold risk. PMID- 1619687 TI - Frequency of thyroid cancer in Pacific populations. PMID- 1619686 TI - Parity and primary liver cancer among young women. PMID- 1619688 TI - Asbestos-related cancer. PMID- 1619689 TI - [Basic educational materials for the members of the Japanese Society of Toxicological Sciences]. PMID- 1619690 TI - Role of sympathetic nerve and adrenal gland in the potentiation of hypoxic pulmonary vasoconstriction during cigarette smoking. AB - The aim of this study was to investigate the role of sympathetic nerve and adrenal gland in the changes in hemodynamics and hypoxic pulmonary vasoconstriction (HPV) induced by cigarette smoking in Wistar rats. Data showed that an increment of pulmonary vascular resistance (PVR) induced by alveolar hypoxia was partially prevented by prazosin (alpha 1-receptor blocker) and prazosin combined with propranolol (beta-receptor blocker), but not significantly affected by propranolol or adrenalectomy. Cigarette smoking could increase PVR and potentiate HPV, whereas the potentiation of HPV was partially inhibited by prazosin and strengthened by propranolol, but not affected by adrenalectomy. It is suggested that the sympathetic nerve excitation caused by cigarette smoking may play a role in the strengthening of HPV. PMID- 1619691 TI - Effect of endotoxin on hypoxic pulmonary vasoconstriction--the role of prostaglandins and leukotrienes. AB - In this study, we observed the effect of endotoxemia on hypoxic pulmonary vasoconstriction (HPV) in dogs and explored roles played by prostaglandins and leukotrienes in this process. 5 micrograms/kg BW of E. coli endotoxin induced transient rise in pulmonary arterial pressure and pulmonary vascular resistance (PVR). 30 min after injection of endotoxin when PVR tended to decline, pulmonary vasoconstriction response to alveolar hypoxia was lost, and the ratio of TXB2 to 6-keto-PGF1 alpha decreased significantly. HPV was enhanced at 60-100 min and then returned to the control level at 2 h after injection of endotoxin. At these periods the ratio of TXB2 to 6-keto-PGF1 alpha was the same as before use of endotoxin, whereas plasma concentration of leukotrienes was markedly increased. Indomethacin could prevent the early loss of HPV, but no effect on the late increment of HPV was found. Diethylcarbamazine, which blocked the production of leukotrienes after use of endotoxin, could inhibit late increment of HPV. We concluded that the early loss of HPV was related to the vasodilator prostacyclin, and the late increment of HPV was mainly brought about by leukotrienes. PMID- 1619692 TI - An image analysis on pathological changes in pulmonary arteries in chronic obstructive pulmonary disease. AB - The changes in small pulmonary arteries of 15 patients with chronic obstructive pulmonary disease (COPD) were investigated by light and electron microscopy, image analysis etc. It was found that the structural changes in the pulmonary arteries of the patients with COPD were characterized by muscularization of non muscular arterioles, media hypertrophy, longitudinal smooth muscle bundles in the intima and fibrosis in both the media and intima. In the course of time, these lesions resulted in thickening of the arterial wall and narrowing of the lumen. Clinically, the patients developed pulmonary hypertension causing cor pulmonale. Initial data on the structure of arterial wall at different segments were compared statistically. There was very significant difference between the COPD and control groups (P less than 0.001). By Fisher's auto-classification (automatic pattern recognition), the rate recognized was correct in more than 90% in the small arteries of less than 200 microns in diameter. It is suggested that these arteriolar changes are closely related to pulmonary hypertension. The image analysis showed that the ratios of MWA/MVA and MWT/MD were of great value in evaluating the degree of the changes in the arteries of the patients with COPD. PMID- 1619693 TI - Investigation on the effect of selenium on T lymphocyte proliferation and its mechanisms. AB - The effects of selenium on T lymphocyte proliferation and its mechanisms have been investigated. The results showed that selenium is able to enhance lectin stimulated T lymphocyte proliferation, to increase the production of interleukin 2 (IL-2) by lymphocytes and interleukin 1 (IL-1) by macrophages in the presence of lectin and to augment the response of T lymphoblasts to IL-2 and that of thymocytes to IL-1. The data presented suggest that selenium may be an important modulator for immune response. Selenium might enhance IL-2 production and response through the augmentation of IL-1 production and response, thereby promoting the enhancement of the proliferation and action of T lymphocytes and other immunocompetent cells. Based on these results, we may consider using selenium as an immunological enhancement agent to enhance or recover immune functions of the organism. PMID- 1619694 TI - Inhibitory effect of cyclosporin A on T lymphocyte DNA synthesis. AB - The interference of Cyclosporin A (CyA) with peripheral lymphocytes DNA synthesis was investigated. The results showed that the drug could strongly inhibit T cell proliferation in response to PHA stimulation if added at the start or at the early phase of the process, and it failed to do so if added 48 h later when most cells had already started to proliferate. Without PHA, no obvious differences were detected between normal control and CyA-treated cells. A comparison was made between T cell DNA synthesis of peripheral blood lymphocytes of healthy volunteers and renal transplant patients. It was found that T-cell DNA synthesis of patients was significantly lower than that of the healthy controls. From the above it may be suggested that CyA activity on T cell proliferation is similar in vivo and in vitro. PMID- 1619696 TI - [1585 cases of retinal detachment surgery with homologous skin as buckling material]. AB - From January 1963 to December 1989, 1585 consecutive cases of retinal detachment were operated with homologous skin as buckling material, the rate of operative success being 91.6%. Human skin is easy to obtain, sterilize and preserve; because of its appropriate thickness and firm but elastic consistency it satisfactorily meets the need to produce sufficient height and to maintain necessary duration of the scleral buckling; in addition to a high rate of reattachment, homologous skin implantation was well tolerated, very rarely rejected (0.06%) and infected (0.25%), and no late complications occurred. Therefore, the authors prefer using human skin as buckling agent rather than conventional synthetic material, e.g., silicon sponge etc. PMID- 1619695 TI - Analysis of intrahepatic HBVDNA in serologic HBV markers-negative or HBsAg negative patients with chronic hepatitis. AB - To explore HBV infection status in a group of serologic HBV markers-negative or HBsAg-negative patients with chronic hepatitis, in situ hybridization to hepatocellular HBVDNA was carried out in combination with detection of HBsAg and HBcAg in the liver tissues. It was found that prevalence of intrahepatic HBVDNA, HBsAg and HBcAg was 43%, 39% and 17% respectively, and 15 out of 23 cases studied were sure to bear one or more positive marker(s) of intrahepatic HBVDNA, HBsAg and HBcAg. These findings suggest that more than half of the patients with chronic hepatitis were still undergoing HBV infection, despite serologic HBV markers or HBsAg negative. Furthermore, we found that hepatocytes containing HBVDNA or surface or core antigen were often close to hepatic necrosis foci, indicating that HBV replication and its antigen(s) expression in hepatocytes could account for chronic, active and necrotic inflammation occurring in the liver of the patients mentioned above. PMID- 1619697 TI - [Influence of cigarette smoking on the hypoxic pulmonary vasoconstriction in isolated rat lungs--the role of prostaglandins and leukotrienes]. AB - Isolated rat lungs perfused with blood were used to determine the effects of cigarette smoke, delivered into the lung by a ventilator, on the pulmonary vascular resistance (PVR), and on the hypoxic pulmonary vasoconstriction (HPV), and to explore the role the prostaglandins (PG) and leukotrienes (LT) play in that effect. The results showed that PVR did not change, while HPV was significantly enhanced by smoking. Indomethacin, an inhibitor of PG biosynthesis, administered in the perfusing blood (20 micrograms/ml) increased HPV in non smoking lungs, but not in lungs after smoking. Diethylcarbamazine citrate (DEC; 1 mg/ml), an inhibitor of LT biosynthesis, decreased HPV before and after smoking. After perfusion with both indomethacin and DEC, HPV also decreased. It is suggested that LT act as mediators whereas PG as modulators in HPV, and PG and LT might play an important role in the increase of HPV by cigarette smoking. PMID- 1619699 TI - Effect of periodontal disease on the pulp. PMID- 1619698 TI - [Histochemical study of estrogen and progesterone receptors in cervical carcinoma]. AB - Estrogen and progesterone receptors were determined in 56 cases of primary cervical carcinoma tissue by histochemical methods. 42.86% of the 56 cases were ER positive and 46.43% PR positive. No correlation was found between ER and PR status and age, menopausal status of the patient and clinical stage. Adenocarcinoma had significantly higher ER and PR positive rate than squamous carcinoma. Highly differentiated carcinoma had higher ER and PR positive rate than middle- and dedifferentiated carcinoma. A positive correlation between ER and PR and cellular infiltration of stroma and peritumoral reaction of fibrin was found. The patients with ER and PR positive had a significantly higher 5-year survival. ER and PR may be used as prognostic factors in cervical carcinoma. PMID- 1619700 TI - Women's perceptions of caesarian delivery. AB - A Perception of Caesarian Delivery Scale that measured the incidence and severity of perceptions and feelings in response to recent Caesarian delivery was administered to 60 mothers who had had Caesarian sections. The scores obtained from this scale were analyzed by factor analysis to determine the relationships within categories of responses, and were analyzed by one-way ANOVA to measure any variation among different demographic groups. A reliability coefficient of 0.93 was obtained for this scale. Factor analysis of the quantitative data defined four categories of women's perceptions associated with Caesarian delivery. Each of the four categories were labeled and discussed. However, there were no significant differences in factor scores between groups with different parities, types of anesthesia, and types of Caesarian section. PMID- 1619701 TI - Incidence and antimicrobial resistance of Salmonella serotypes in southern Taiwan from 1978 through 1987. AB - A total of 3,269 Salmonella strains, isolated from patients suffering from salmonellosis, was divided into 43 different serotypes during the period between 1978 and 1987. The commonest ten serotypes in the order of prevalence were S. typhimurium (43.7%), S. muenchen (13.7%), S. panama (9.0%), S. krefeld (8.1%), S. bovis-morbificans (6.3%), S. derby (4.0%), S. anatum (2.7%), S. braenderup (1.6%), S. typhi (1.2%), and S. dumfries (0.7%). Norfloxacin was found highly effective against Salmonella isolates in vitro. Moxalactam and cefotaxime were more effective than cephalothin against strains tested. Nalidixic acid and trimethoprim-sulfamethoxazole inhibited 81-100% strains of Salmonella isolates, except S. bovis-morbificans and S. typhimurium. In general, S. typhimurium showed high incidence of multiple drug resistance. Among 1,430 strains of S. typhimurium, 158 isolates showed a uniquely high level resistance to a number of antimicrobial agents, including ampicillin, amikacin, carbenicillin, cephalothin, chloramphenicol, gentamicin, kanamycin, tetracycline and trimethoprim sulfamethoxazole. It was noted that all S. typhi isolates in this study were sensitive to all drugs tested. PMID- 1619702 TI - Studies of taeniasis in Taiwan. XIV. Current status of taeniasis among Yami aborigines on Lanyu Island, Taitung County, southeast Taiwan. AB - In December 1989, 1,457 Yami aborigines in six villages on Lanyu District (Lanyu Island), Taitung County, Southeast Taiwan, were examined by questionnaire and demonstration of the proglottides or by scotch tape perianal swab technique for taeniasis. The overall infection rate was 5%. The highest rate was found at Yehyin (8%) and the lowest at Yujen (2%). However, the rate did not significantly differ among the villages. The infection rate peaked in the 51-60 yr age group (15%) and the lowest rate was observed in the 11-20 yr age group (less than 1%). No infection was found in the 21-30 yr age group. The infection rates of men and women were similar (5%). Twenty-one per cent of 304 families was found to include one or more infected members and a family with five infected person was observed at Yehyin. The infection rate of taeniasis on Lanyu Island decreased from 16% in 1984 to 5% in 1989. However, 51 persons who were negative in 1984 were positive at present, 26 were found to be positive in both studies, and 216 (12 died) who were positive in 1984 were now negative. These results indicate that the Yami people still eat raw meat and viscera of animals. PMID- 1619703 TI - Comparison between thallium-technetium subtraction scan and other imaging modalities in the preoperative localization of abnormal parathyroid glands. AB - A total of 15 patients who underwent total neck exploration for hyperparathyroidism were studied with four different imaging modalities: (a) Tl 201/Tc-99m subtraction scan (SS), (b) ultrasonography (US), (c) computed tomography (CT) and (d) magnetic resonance imaging (MRI). Accuracy for locating enlarged parathyroid(s) was 60.0% by SS, 60.0% by US, 33.3% by CT and 71.4% by MRI. Our results suggested that at present none of the imaging modalities was adequate on its own to locate all enlarged parathyroid gland(s) in patients with hyperparathyroidism. PMID- 1619704 TI - The contralateral variation of peak systolic velocity in common carotid arteries. AB - In order to evaluate the contralateral variation of the peak systolic velocity (Vmax) in common carotid arteries (CCAs), 9 clinically healthy persons (Group A), 11 patients with simple goiter (Group B) and 16 patients with diffuse toxic goiter (Graves' disease, Group C) were referred for radionuclide scanning, duplex Doppler ultrasonography (duplex US) and determination of serum level of the thyroid hormones (T3, T4, T3U) by radioimmunoassay. In Group A, Vmax of right CCA was 98.8 +/- 34.5 cm/sec and that of left CCA was 113.4 +/- 28.9 cm/sec; the left CCA had a higher blood flow velocity than the right one in normal subjects (p less than 0.01). However, the left and right CCA Vmaxes did not significantly differ to each other in Group B (93.5 +/- 21.4 cm/sec vs 98.6 +/- 21.4 cm/sec, p greater than 0.05) and Group C (146.9 +/- 29.3 cm/sec vs 149.9 +/- 28.9 cm/sec, p greater than 0.05). We conclude that there is a contralateral difference of blood flow velocity of common carotid arteries with the left value higher than the right one in healthy persons and this should be kept in mind in evaluation of thyroid functional and carotid arterial diseases. PMID- 1619705 TI - Neonatal lupus erythematosus: a case report. AB - Neonatal lupus erythematosus is a syndrome characterized by congenital heart block and/or cutaneous lupus erythematosus in the presence of maternal autoantibodies. We report a female newborn with cutaneous lesions of the neonatal lupus erythematosus born to a clinically asymptomatic mother. She presented with erythematous maculopapules on the face, neck and upper trunk at birth. Complete blood cell count showed leukopenia and thrombocytopenia. Antinuclear antibodies, anti-Ro/SSA and anti-La/SSB antibodies were positive in the mother and infant. The skin lesions became annular, erythematous and slightly scaling three weeks later. A skin biopsy performed at seven weeks of age showed edema of the dermis and perivascular mononuclear cell infiltration. Immunofluorescent studies showed immune complex deposition of IgG an IgM in the basal zone of epidermis. She received supportive treatment and sun avoidance. Hematologic abnormalities recovered by nine weeks of age. Skin lesions faded gradually during the following four months, leaving residual hypopigmentation and telangiectasia. PMID- 1619706 TI - Microsurgical replantation of avulsed scalp--two cases report. AB - Two female patients with scalp avulsion were treated successfully by microsurgical replantation. The first patient suffered an avulsion of the right half of scalp and which survived fully after replantation. The second patient suffered avulsion of the entire scalp as well as the forehead skin and nape of the neck. Almost all of the avulsed part survived except partial skin loss in the posterior neck and left occipital area. Only one temporal artery and one vein was anastomosed in each case. Near normal hair growth recurred in both cases. PMID- 1619707 TI - Jugular venous vasopressin increases during carotid endarterectomy after cerebral reperfusion. AB - Several recent reports have suggested that pressor hormones may be released during and after carotid endarterectomy and that release of these factors may be associated with postoperative hypertension and other postoperative morbidity. We measured vasopressin, adrenocorticotropic hormone, and cortisol in jugular venous blood during carotid endarterectomy under general anesthesia in 43 patients with routine carotid shunting. Jugular venous vasopressin increased significantly after the second period of carotid occlusion for shunt removal and remained increased at closure. Vasopressin did not change during the initial carotid occlusion for shunt placement or during the endarterectomy itself, and neither ACTH nor cortisol changed at any sample time. Greater resting vasopressin and cortisol and larger responses of vasopressin were observed in patients receiving phenylephrine to correct intraoperative hypotension. There were no correlations between postoperative hypertension or postoperative complications and intraoperative hormone values. These results suggest (1) basal intraoperative vasopressin values reflect the blood volume of the patient, (2) increased vasopressin was not related to postoperative morbidity, and (3) intraoperative increases in pressor hormones are most likely physiologic responses to specific stimuli such as hypovolemia or hypotension rather than pathologic phenomena. We speculate that the increase of vasopressin after the second carotid occlusion and reperfusion of the brain may be due to the action of humoral factors released into the carotid circulation from the endarterectomy site. PMID- 1619708 TI - Validation of Doppler measurement of pressure gradients across peripheral model arterial stenosis. AB - Hemodynamic assessment of aortoiliac occlusive disease is necessary for successful arterial reconstruction of the legs. Various methods have been proposed, and the "pull through" intraarterial pressure measurement method is accepted as the best standard. The pressure readings, however, seemed to depend on the intraluminal position of the catheter. To explain these observations and make a comparison between the Doppler method and the pull through method, we have studied centerline velocity changes at the stenosis throat by Doppler ultrasonography, and axial and lateral pressure gradients by use of pressure transducers mounted 10 mm and 40 mm downstream of short (4 mm) axisymmetric sharp edged model stenoses having cross-sectional reduced areas of 64%, 84%, 91%, and 96%. Axial manometric pressures measured 10 mm beyond the throat of 84% stenosis were more than twice as high as the lateral pressures. No significant difference was observed between axial and lateral pressures measured 40 mm downstream from the throat. This pressure distribution has important clinical relevance. Mean and peak pressure gradients for both the Doppler method and manometric measurements were compared. Measurements with Doppler method and manometric measurements indicated that mean pressure gradients (r = 0.98; SEE = +/- 2.4 mm Hg) correlate better than peak pressure gradients (r = 0.90; SEE = +/- 16.5 mm Hg). Doppler gradients were higher than manometer gradients. Overestimation was 13% for mean pressure gradients and ranged from 10% to 150% for peak pressure gradients. Explanation for the difference between mean Doppler and catheter gradient may be the pressure recovery occurring in the relaminarized poststenotic regions. PMID- 1619709 TI - Congenital pelvic arteriovenous malformations: long-term follow-up in two cases and a review of the literature. AB - Congenital arteriovenous malformations confined to the soft tissues of the pelvis are rare and challenging lesions. Multitudinous embryonic macrocommunication and microcommunication between the arterial and venous systems, with resultant shunting of blood to the low-resistance veins, produce massive venous and tissue engorgement. No well-established guidelines exist concerning their management. Percutaneous arterial embolization and surgery are associated with high recurrence rates. Surgical excision is frequently not possible and can result in massive hemorrhage. Only 52 cases have been reported in the English-language literature, and only two patients were followed for longer than 6 years. This report presents two additional patients with massive pelvic arteriovenous malformations monitored for 9 and 17 years. One patient was initially treated with arterial percutaneous embolization and the other with attempted operative ablation. A review of the literature has allowed us to develop the following management guidelines: Asymptomatic, nonenlarging lesions require no intervention and can be safely followed by clinical and radiologic (ultrasonography, CT scanning) examinations every 6 months. Symptomatic or rapidly enlarging lesions should be treated with preoperative arterial embolization and surgical excision attempted only if the arteriovenous malformation is localized and does not involve adjacent organs. Arterial embolizations may be repeated to provide symptomatic relief of diffuse, large lesions that involve the bladder or bowel. This protocol will avoid unnecessary and frequently life-threatening surgery in the management of pelvic arteriovenous malformations. PMID- 1619711 TI - Small-bowel obstruction from an extruded Greenfield filter strut: an unusual late complication. AB - Recently interest has been shown in liberalizing the indications for insertion of vena caval filters. The convenience of percutaneous insertion by radiologists may further perpetuate this trend. However, filter placement is not without morbidity. We report a unique late complication in which a small-bowel obstruction occurred as a result of volvulus around an extruded filter strut. PMID- 1619710 TI - Acute mesenteric ischemia caused by isolated superior mesenteric artery dissection. AB - Isolated dissection of a peripheral artery is a rare event. Only 11 reports exist in the literature of dissection of the superior mesenteric artery, most of which have been fatal. This is the first documented case of the successful treatment of an acute ischemic event caused by a superior mesenteric artery dissection. In addition, the new technique of right gastroepiploic artery-to-superior mesenteric artery bypass is introduced as a satisfactory method of revascularization. PMID- 1619712 TI - Intermittent claudication caused by compression of tibial vessels as a result of calf muscle hypertrophy: case report. AB - We present a case with findings suggestive of popliteal artery entrapment in a patient with intermittent claudication and localized muscle hypertrophy in the calf muscles after removal of a herniated disk. Angiography failed to demonstrate popliteal artery entrapment but instead revealed compression of the tibial vessels caused by calf muscle hypertrophy. The concept of muscle hypertrophy caused by denervation is also discussed. PMID- 1619713 TI - Thorascopic dorsal sympathectomy for hyperhidrosis: a new approach. PMID- 1619714 TI - A prospective randomized trial of autologous platelet-derived wound healing factors for treatment of chronic nonhealing wounds: a preliminary report. PMID- 1619715 TI - A prospective randomized trial of autologous platelet-derived wound healing factors for treatment of chronic nonhealing wounds: a preliminary report. PMID- 1619716 TI - A prospective randomized trial of autologous platelet-derived wound healing factors for treatment of chronic nonhealing wounds: a preliminary report. PMID- 1619717 TI - Saddle embolism complicating Candida parapsilosis aortic valve endocarditis: cure with aortic valve replacement and prompt extraction of multiple mycotic emboli. PMID- 1619718 TI - Right subhepatic approach for inflammatory aortic aneurysm in a patient with scoliosis. PMID- 1619719 TI - Vascular complications of cardiac catheterization. PMID- 1619720 TI - Clinical, hemodynamic, and anatomic predictors of long-term outcome of lower extremity venovenous bypasses. PMID- 1619721 TI - Misdiagnosis of ruptured abdominal aortic aneurysms. AB - Ruptured abdominal aortic aneurysm is a surgical emergency with a high mortality rate even when diagnosed and repaired immediately. We retrospectively reviewed 152 cases of ruptured abdominal aneurysms to identify the incidence of misdiagnosis leading to a delay in treatment, the most frequent misdiagnoses, and the outcome in this group of patients. Forty-six (30%) were initially misdiagnosed. The most common misdiagnoses were renal colic, diverticulitis, and gastrointestinal hemorrhage. The most common initial physical findings in misdiagnosed patients were abdominal pain (70%), shock (57%), and back pain (50%). A pulsatile abdominal mass was found in only 26% of misdiagnosed patients versus 72% of patients correctly diagnosed (p less than 0.005). Misdiagnosed ruptured abdominal aneurysm had a 44% mortality rate, which was not significantly different from patients correctly diagnosed (58%, p = 0.34). The lack of difference in mortality rates is most likely due to preselection of those misdiagnosed patients who were able to withstand the delay in diagnosis and survive to surgical treatment. The 30% incidence of misdiagnosis in this series suggests that it is frequently a difficult diagnosis to make and must be considered in elderly patients, especially men, who are admitted with abdominal pain and/or back pain. PMID- 1619722 TI - The profunda femoris: a durable outflow vessel in aortofemoral surgery. AB - Aorta-common femoral artery bypass is the standard operation for relief of aortoiliac occlusive disease. When extensive superficial femoral artery disease coexists, the profunda femoris, even in its distal portion, may be used as the outflow vessel. To test this assumption we compared cumulative patency, limb salvage, and the need for distal bypass of 134 aorta-profunda femoris and 151 aorta-common femoral artery bypasses performed consecutively for aortoiliac occlusive disease over a 12-year period. We also analyzed results of proximal (n = 103) and distal (n = 31) aortoprofunda bypasses. Angiographic and noninvasive studies showed greater disease in limbs undergoing aorta-profunda femoris bypass. However, no difference was observed in cumulative patency (91% +/- 6% vs 96% +/- 3%) or limb salvage (90% +/- 6% vs 94% +/- 3%) at 5 years. Seventeen distal bypasses in the group undergoing profunda femoris bypass and 20 distal bypasses in the group undergoing common femoral artery bypass were required to maintain limb salvage. Proximal and distal aorta-profunda femoris bypasses showed no difference in cumulative patency (91% +/- 9% vs 95% +/- 6%) or limb salvage (94% in each group) at 3 years. Standard aorta-common femoral artery and aorta profunda femoris bypass provide cumulative patency and limb salvage exceeding 90% at 5 years; concomitant or subsequent distal bypass was required in 12% or limbs undergoing aorta-profunda femoris bypasses. Both proximal and distal profunda femoris arteries provide a durable outflow tract when aortoiliac and femoropopliteal occlusive disease are combined. PMID- 1619723 TI - Medial calf perforators in venous disease: the significance of outward flow. AB - The role of medial calf perforators in the initiation or promotion of venous disease is incompletely understood. The purpose of this study was to define the direction of blood flow in the perforating vein of the calf in normal limbs and in those limbs of patients with venous disease under defined laboratory conditions. Both lower limbs of 57 patients, (32 women and 25 men, median age, 56 years; range, 40 to 62 years) were examined by duplex ultrasonography. In 10 patients no clinical or duplex evidence existed of venous disease. In 60 legs we found evidence of superficial venous insufficiency, complicated by lipodermatosclerosis in 29. In 15 limbs we found deep venous insufficiency. Finally, in 19 limbs no evidence existed of venous disease, but venous reflux was present in the contralateral limb. The direction of blood flow in the medial calf perforators was assessed during compression of the foot and calf, by a cuff that inflated to 60 mm Hg. Blood flow was also assessed during deflation of the cuff. We found that the direction of blood flow within medial calf perforators can be both inward or outward, even in limbs without evidence of venous disease. Outward flow could be demonstrated in 21% of perforators in normal limbs. Flow on release of distal compression occurred in 33% to 44% of perforators in limbs with evidence of venous disease but in none of the perforators in limbs without evidence of venous disease. We found that flow, during the relaxation phase, within medial calf perforators was associated with venous disease elsewhere in the limb. PMID- 1619724 TI - Heparin-mediated reductions of the toxic effects of protamine sulfate on rabbit myocardium. AB - Protamine sulfate causes direct myocardial suppression when used to reverse heparin anticoagulation. Protamine's excessive positive charge accompanying its surface arginine groups appears to be responsible for this toxicity. This study was designed to assess the hypothesis that negatively charged heparin given after protamine exposure may enhance the recovery of protamine-induced myocardial dysfunction. Isolated rabbit hearts (n = 20) were perfused with physiologic saline solution at 80 to 90 mm Hg containing high dose protamine, 250 micrograms/ml, until heart contraction essentially ceased (baseline). Hearts were then randomly reperfused for 15 minutes with either physiologic saline solution (group I, n = 10) or heparin plus physiologic saline solution (group II, n = 10) at a dose of 0.1 IU/1.0 microgram of previously administered protamine. Developed left ventricular blood pressure, heart rate, pulmonary artery PaO2, contractility (+dp/dt), oxygen extraction (AvO2), oxygen consumption (VO2), and rate x pressure product were assessed. A protective, beneficial response accompanied heparin administration (group II) in all functions assessed except blood pressure. Maximum changes, comparing group I with II, were heart rate (beats/min) -72 versus -1, p less than 0.001; +dp/dt -64% versus -51%, p less than 0.01; PaO2 +86% versus +9%, p less than 0.001; AvO2 -37% versus -4%, p less than 0.001; VO2 50% versus -28%, p less than 0.008; and rate x pressure product -73% versus -51%, p less than 0.001. These data suggest a separation of protamine's hemodynamic effects (blood pressure) and metabolic effects (VO2). Furthermore, these data support the tenet that heparin is able to markedly lessen the toxic myocardial effects of protamine. PMID- 1619725 TI - Assessment of quality of life of patients with severe ischemia as a result of infrainguinal arterial occlusive disease. AB - The purpose of this cohort study was to assess the quality of life of patients with severe ischemia as a result of infrainguinal arterial occlusive disease. Spitzer's QL-INDEX was selected to measure quality of life at baseline and at 3, 6, and 12 months. On the basis of initial treatment, 61 patients were grouped as follows: IC (conservative, n = 31), IR (arterial reconstruction, n = 14), and IA (major amputation, n = 16). After 12 months of follow-up, 48 patients were similarly regrouped according to ultimate treatment as follows: UC (n = 19), UR (n = 9), and UA (n = 20). At 12 months the mean score was significantly higher than the baseline in IC (6.43 vs 3.84, p less than 0.0001) as well as IR (5.64 vs 3.57, p less than 0.01), but not in IA (4.43 vs 3.62). The QL-INDEX mean score was lower in UA than in UC (4.15 vs 6.58, p less than 0.01) or UR (4.15 vs 7.11, p less than 0.0001). The correlation between QL-INDEX and an arbitrary scale was also high (r = 0.726, p less than 0.001). In conclusion, quality of life of patients with limb ischemia can be confidently assessed, improves during the first year of follow-up if major amputation is avoided, and improves and is sustained by a functioning graft. PMID- 1619726 TI - Fibromuscular dysplasia of the brachial artery: a case report and review of the literature. AB - Fibromuscular dysplasia is a nonatherosclerotic, noninflammatory vascular disease that involves primarily medium-sized and small arteries. Fibromuscular dysplasia is characterized by medical fibrosis with or without smooth muscle cell hyperplasia and may produce luminal impingement with severe turbulence. Secondary aneurysmal deformity with or without thrombosis may also contribute to the obstruction. Fibromuscular dysplasia most commonly involves the renal and carotid arteries, with upper-extremity disease rarely reported. This case report describes a patient with digital embolization from brachial artery fibromuscular dysplasia. Angiography demonstrated significant narrowing and irregularity with a characteristic "string-of-beads" appearance of the right midbrachial artery. The abnormal segment was resected and reconstructed with a reversed saphenous vein graft. Histologic studies revealed disruption of the internal elastic lamina and disorientation of the hyperplastic medial smooth muscle cells characteristic of fibromuscular dysplasia. PMID- 1619727 TI - Mycotic aneurysm of the tibioperoneal trunk: case report and review of the literature. AB - Peripheral mycotic aneurysms can occur when septic emboli lodge in either the lumen or the vasa vasorum of a peripheral vessel. Such aneurysms have become rare after the widespread use of aggressive antibiotic treatment for bacterial endocarditis. We report the case of a large mycotic aneurysm of the tibioperoneal trunk 18 months after an episode of Streptococcus viridans bacterial endocarditis. Treatment included complete resection of the aneurysmal sac with restoration of circulation to the posterior tibial artery with a reversed saphenous vein graft. To our knowledge, this is the first case of a mycotic aneurysm of the tibioperoneal trunk reported in the English literature. It also represents the first case in which a mycotic aneurysm of an infrapopliteal vessel was managed successfully with restoration of circulation. PMID- 1619728 TI - Thoracoabdominal aortic aneurysm associated with umbilical artery catheterization: case report and review of the literature. AB - Aneurysms in infants and children are rare and are usually associated with cardiovascular malformations or connective tissue disorders. A new subgroup of patients has become recognized over the past two decades--those with aneurysms associated with umbilical artery catheterization. Critically ill newborns who have required umbilical artery catheterization and have developed sepsis, usually staphylococcal, are at risk for the development of mycotic aneurysm disease of the aorta or its major branches or both. Since first described in 1970, 34 cases have been reported in the literature, 14 involving the descending thoracic aorta, 10 the abdominal aorta, 6 the iliac arteries, and 4 either the thoracoabdominal aorta or multiple aneurysms involving both the thoracic and abdominal aorta. This report presents a case we recently treated of a 15-month-old-boy with a large thoracoabdominal aortic aneurysm and aneurysms of the infrarenal abdominal aorta and proximal right common iliac artery. It includes a review of the recent literature to analyze pathogenesis, clinical manifestations, and to formulate methods of treatment. PMID- 1619729 TI - Blunt traumatic iliac vein laceration without pelvic fracture: a rare entity. AB - Most blunt traumatic pelvic venous injuries are associated with pelvic fractures. We report the case of a 32-year-old man who suffered a common iliac vein laceration, without a pelvic fracture, during a motor vehicle accident. Laparotomy and venous repair were undertaken. PMID- 1619730 TI - Aortoesophageal fistula: report of a successfully managed case and review of the literature. AB - Aortoesophageal fistula is a rare, frequently fatal cause of upper gastrointestinal bleeding. Although several causes have been described, it appears that the most common cause is rupture of a thoracic aortic aneurysm into the esophagus, occurring in approximately 12% of thoracic aneurysm ruptures. Although the entity was originally described in 1818, the diagnosis has rarely been made before death, and until 1983 no one survived surgery for aneurysm associated aortoesophageal fistulas. Since that report of two cases, only two other survivors, including this patient, have been reported. Included herein is the report of a successfully managed case, along with a discussion of the causes, clinical features, and diagnostic approach to the disease, as well as the management of both the aortic and esophageal components of the fistula. PMID- 1619731 TI - A complication of the Greenfield filter: fracture and distal migration of two struts--a case report. AB - This is a case report of a 41-year-old woman who required surgical removal of a Greenfield filter 7 months after placement. The filter developed several complications. Two struts were noted to be completely separated from the filter and lodged in the infrarenal vena cava. The filter had migrated to a resting position in the right renal, vein with two struts perforating the renal vein and inferior vena caval junction. The perforating struts were intraperitoneal and were found to impinge on the right ureter with seromuscular involvement of the second portion of the duodenum. No free perforation was noted at the time of exploration. PMID- 1619732 TI - Violence decreases with gang truce. PMID- 1619733 TI - 'Critical moment' at hand in HIV/AIDS pandemic, new global strategy to arrest its spread proposed. PMID- 1619734 TI - From the Centers for Disease Control. Selected tobacco-use behaviors, dietary patterns among high school students--United States, 1991. PMID- 1619735 TI - From the Centers for Disease Control. Unintentional firearm-related fatalities among children, teenagers--United States, 1982-1988. PMID- 1619736 TI - From the Centers for Disease Control. Public health focus: mammography. PMID- 1619737 TI - A piece of my mind. Monday morning clinic. PMID- 1619739 TI - DEXA. PMID- 1619738 TI - The quality of mercy is not strained. PMID- 1619740 TI - A survey of occupational blood contact and HIV infection among orthopedic surgeons. The American Academy of Orthopaedic Surgeons Serosurvey Study Committee. AB - OBJECTIVE: To study the seroprevalence of human immunodeficiency virus (HIV) among orthopedic surgeons, and correlate the results with occupational and nonoccupational risk factors. Orthopedic surgeons are one of several groups of health care workers at risk for occupationally acquired HIV infection; however, few HIV seroprevalence studies in health care workers, and none in surgeons, have been performed to assist in estimating the extent of occupational risk. DESIGN: A voluntary, anonymous HIV serosurvey at an annual meeting. To assess the representativeness of participants, a mail survey of orthopedic surgeons was conducted 5 months prior to the annual meeting. SETTING: The 1991 annual meeting of the American Academy of Orthopaedic Surgeons held in Anaheim, Calif. PARTICIPANTS: United States or Canadian orthopedic surgeons in training, in practice, or retired from practice who attended the annual meeting. MAIN OUTCOME MEASURES: Participants' HIV serostatus and reporting of occupational and nonoccupational risk factors for HIV infection. RESULTS: Of 7147 eligible orthopedists at the annual meeting, 3420 (47.9%) participated. Compared with the 10,411 orthopedic surgeons responding to the mail survey, serosurvey participants had at least as many opportunities for occupational contact with blood and with HIV-infected patients. Among participants, 87.4% reported a blood-skin contact and 39.2% reported a percutaneous blood contact in the previous month. Among 3267 participants without reported nonoccupational risk factors for HIV infection, none was positive for HIV antibody (0%; upper limit of the 95% confidence interval [CI] = 0.09%); among 108 participants with reported nonoccupational HIV risk factors, two were positive for HIV antibody (1.9%; upper limit of the 95% CI = 5.7%). CONCLUSION: Although these findings may not be generalizable to all orthopedic surgeons, we found no evidence of HIV infection among serosurvey participants without nonoccupational risk factors. The high rates of self reported blood contact underscore the importance of compliance with infection control precautions and of development of new techniques and equipment to minimize the risk of exposures to blood during surgical procedures. PMID- 1619741 TI - Population-based monitoring of an urban HIV/AIDS epidemic. Magnitude and trends in the District of Columbia. AB - OBJECTIVE: To assess the extent of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic in the District of Columbia and demonstrate an approach to monitoring HIV infection and projecting AIDS incidence at a community level. DESIGN: Backcalculation methods to reconstruct HIV incidence from AIDS incidence in subgroups. Results were compared with directly measured HIV seroprevalence in selected sentinel populations: childbearing women, civilian applicants for military service, and hospital patients admitted for conditions unrelated to HIV infection. RESULTS: Between the start of the epidemic in 1980 and January 1, 1991, one in 57 District of Columbia men aged 20 to 64 years was diagnosed with AIDS. Unlike the plateau projected for the nation, AIDS incidence for the District of Columbia was projected to increase by 34% between 1990 and 1994. Models of HIV infection incidence suggested two broad epidemic waves of approximately equal size. The first occurred in men who have sex with men and peaked during the period from 1982 through 1983. The second began in the mid-1980s in injecting drug users and heterosexuals. We estimated that among District of Columbia residents aged 20 to 64 years, 0.3% of white women, 2.9% of white men, 1.6% of black women, and 4.9% of black men were living with HIV infection as of January 1, 1991. These estimates are broadly consistent with survey data: among black childbearing women in their 20s, HIV prevalence doubled to 2% between the fall of 1989 and the spring of 1991; from military applicant data, we estimated that over 5% of black men born from 1951 through 1967 were HIV-positive; in the sentinel hospital, HIV prevalence rates among male patients aged 25 to 34 years were 11.3% in white men and 16.9% in black men. CONCLUSION: Backcalculation and surveys yielded quantitatively consistent estimates of HIV prevalence. Many injecting drug users and heterosexuals in the District of Columbia were infected after January 1, 1986. Similar monitoring of the epidemic in other localities is needed to focus efforts to reduce the incidence of HIV transmission. PMID- 1619742 TI - High risk of active tuberculosis in HIV-infected drug users with cutaneous anergy. AB - OBJECTIVES: To determine the incidence of active tuberculosis in human immunodeficiency virus (HIV)-seropositive and HIV-seronegative drug injectors with cutaneous anergy and to examine the effectiveness of isoniazid chemoprophylaxis in preventing tuberculosis among drug injectors with positive tuberculin test results. DESIGN AND SETTING: Prospective observational study linked to an ongoing study of HIV infection within a New York City (NY) methadone program; subjects also underwent routine intradermal tuberculin testing and multiple-antigen delayed-type hypersensitivity skin testing. The 31-month study period ended December 31, 1990. METHODS: Anergic subjects and tuberculin reactors who were HIV seropositive were compared by HIV disease status and CD4+ T lymphocyte levels. Tuberculosis incidence was calculated for anergics (none treated with isoniazid) and for treated and untreated tuberculin reactors, by HIV serological status. RESULTS: Among those seropositive for HIV, anergic subjects had more advanced HIV disease and fewer CD4+ cells (median 0.33 vs 0.56 x 10(9)/L, P less than .01) compared with tuberculin reactors, although neither clinical status nor CD4+ cell counts consistently predicted anergy. Five (7.6%) of 68 anergic subjects who were HIV seropositive and none of 52 anergic subjects who were HIV seronegative (n = 18) or of unknown (n = 34) HIV serological status developed active tuberculosis during the study period (P less than .05). The tuberculosis incidence rate among anergic subjects who were HIV seropositive was 6.6 cases per 100 person-years (95% confidence interval [Cl], 2.1 to 15.3). Of 25 HIV-seropositive tuberculin reactors who did not receive or complete 12 months of isoniazid prophylaxis, tuberculosis incidence was 9.7 cases per 100 person-years (95% Cl, 2.6 to 24.7; P = 0.56, compared with the rate among anergic HIV seropositives); there were no cases of tuberculosis in 53.4 person-years of follow-up for 27 HIV-seropositive tuberculin reactors who received 12 months of prophylaxis (rate difference between treated and untreated groups, 9.7 cases per 100 person-years, 95% Cl, 1.3 to 18.0). CONCLUSION: Drug injectors with cutaneous anergy who are seropositive for HIV are at high risk of active tuberculosis, similar to that among untreated HIV-seropositive tuberculin reactors. A decreased incidence of active tuberculosis was seen in HIV-seropositive tuberculin reactors receiving 12 months of isoniazid chemoprophylaxis, compared with untreated or partially treated subjects. These results support the routine use of delayed-type hypersensitivity testing to accompany tuberculin testing for drug injectors with known or suspected HIV infection, and consideration of isoniazid prophylaxis for anergic as well as tuberculin-reactive subjects who are HIV seropositive, in populations with a high prevalence of coexisting HIV and Mycobacterium tuberculosis infection. PMID- 1619743 TI - Residents' experiences in, and attitudes toward, the care of persons with AIDS in Canada, France, and the United States. AB - OBJECTIVE: To evaluate resident physicians' experiences in, and attitudes toward, the care of persons with the acquired immunodeficiency syndrome (AIDS) in Canada, France, and the United States. DESIGN: Cross-sectional survey, using a self administered, mailed questionnaire to residents in 10 American states, three French regions, and all 10 Canadian provinces, with follow-up surveys of nonresponders in France and the United States. SUBJECTS: Systematic samples of residents in the last year of internal medicine or family medicine residencies prior to subspecialization or entry into medical practice. RESULTS: While the majority of residents had provided inpatient and outpatient care to persons with AIDS, most believed that their training in ambulatory care of persons with AIDS had been deficient. The rate of blood-contaminated needle-sticks from human immunodeficiency virus-infected patients ranged from 4% for internal medicine residents in Canada to 14% in the United States (P less than .05). The majority recognized an ethical obligation to treat AIDS, but 4% in France, 14% in Canada, and 23% in the United States indicated that they would not care for persons with AIDS if they had a choice (P less than .001). A substantial minority of US physicians reported that a patient of theirs had been refused care by a medical specialist (19%) or a surgeon (39%), but less than 10% of French physicians reported such refusals (P less than .001). CONCLUSION: Concerns about caring for AIDS patients were common and many physicians reported that patients were refused care. While most residents acknowledged an obligation to treat human immunodeficiency virus infection, many did not, and viewpoints varied considerably across the countries studied. The lower level of reluctance to treat AIDS patients in France and Canada makes it clear that the higher rate in the United States is far from optimal and needs to be addressed. PMID- 1619744 TI - The history of malariotherapy for neurosyphilis. Modern parallels. PMID- 1619745 TI - A retreat in the tobacco war. PMID- 1619746 TI - [Autonomic nervous system from a basic aspect]. AB - The autonomic nervous system was reviewed from a basic aspect with particular emphasis on (1) cooperation between the autonomic and somatic nervous systems, (2) necessity for a concept of functional unit of the central and peripheral autonomic nervous systems, and (3) realization of the existence of afferent fibers in the peripheral autonomic nerves. In addition, some recent topics related to the autonomic nervous system on (1) parasympathetic innervation of blood vessels, (2) receptors and intracellular signal transduction system, (3) autonomic regulation of hormonal and immune organs, (4) intracranial neural regulation of cerebral blood flow, and (5) neurotrophic factors are reviewed. PMID- 1619747 TI - [Autonomic reflexes: focusing on the arterial baroreceptor-vasoconstrictor reflex]. AB - The arterial baroreceptor-sympathetic vasoconstrictor reflex (baroreceptor reflex), among autonomic reflexes, is summarized. Arterial baroreceptor afferents terminate in the caudal part of the nucleus tractus solitarius. Excitation of the baroreceptor afferents activates neurons in the caudal ventrolateral medulla that send axonal projections to the rostral ventrolateral medulla. These neurons (CVLM neurons) then inhibit tonic activity of sympathoexcitatory reticulospinal neurons in the rostral ventrolateral medulla (RVLM neurons). Tonic activity of RVLM neurons are responsible for tonic activity of the peripheral vasoconstrictors. These two kinds of neurons are essential neuronal components for the baroreceptor reflex. Both the neurons may also participate in various vasoconstrictor reflexes, such as the somato-and viscero-sympathetic vasoconstrictor reflexes. PMID- 1619748 TI - [Concept and classification of autonomic failure]. AB - The autonomic nervous system innervates every visceral and peripheral organs in the body. It has as complex a neural organization in the brain, spinal cord, and periphery as the somatic nervous system, but remains largely involuntary or automatic. Accurate diagnosis is essential for proper management of autonomic failure but in attempting to classify autonomic disease there is a philosophical point to be borne in mind. Since it is very difficult to comprehend and evaluate systematically the aspect of autonomic dysfunction in each organ in various diseases, little works have been performed to classify autonomic diseases. We introduce several comprehensible works of classification of autonomic failure. We also presented some typical autonomic diseases according to those classifications in this paper. PMID- 1619749 TI - [Diseases of the autonomic nervous system. General aspect of symptomatology]. AB - The human internal environment is regulated by the autonomic nervous system (ANS), endocrine glands and neuropeptides as well as the integrated activity of these three systems. The ANS is divided into thoraco-lumbar (sympathetic) and cranio-sacral (parasympathetic) divisions. They comprise two neurons: pre- and post-ganglionic fibers. The limbic system and hypothalamus are known to regulate the peripheral ANS through descending pathways in the brain stem and spinal cord. Cardinal semiologies of the ANS disorders are classified as follows: cardiovascular (orthostatic hypotension, a variety of syncopes, postprandial hypotension, Raynaud's phenomenon), pupillomotor (paralytic mydriasis, Adie's tonic pupil, Horner's syndrome), urodynamic (urinary retention and incontinence), and sexual (impotence, hyper- and hyposexuality). PMID- 1619750 TI - [Evaluation of autonomic nervous function by pupil dynamics recording]. AB - Pupil is richly innervated by autonomic nerves. Therefore, its size or movement well reflects the autonomic nervous function. By analyzing dynamics of pupil movement for light stimulus followed by infrared video-pupillography, the abnormality of autonomic nervous system can be expressed in a quantitative manner. Clinical applications of pupillography and pharmacological examination to Horner syndrome, Adie syndrome, diabetes mellitus, pupillary involvement of Behcet disease, pupil of brain death and patients with chemical sensitivity have been described. Segmental spasm of iris in Horner and Aide syndrome, especially, nasal side of iridoplegia was seen in early stage of Aide syndrome from pupillary dynamics to light stimulus. An involvement of sympathetic nerve subserving iris dilator muscle was confirmed from pupillography, drug reaction to topically applied l-epinephrine in the diabetics. An involvement of cholinergic nerve which subserve the iris sphincter muscle was seen in Behcet disease when there was no manifest eye involvement. Mild mydriasis in brain death patients was seen under denervation of central nervous system. Dysfunction of sympathetic nerve from pupillary light reflex in chemically sensitive patients for cholinated hydrocarbon pesticides. PMID- 1619751 TI - [Heart rate variability]. AB - Heart rate variability (HRV) has become a useful parameter for the quantification of autonomic nervous function. HRV has been quantified, either by time domain or frequency domain analysis. Time domain measures, such as CVRR and RR50, are easy to calculate but they only provide information related to parasympathetic activity. The spectral analyses, on the other hand, give us information concerning 3 oscillatory components. The high frequency band (the frequency between 0.15-0.5 Hz) is known as the respiratory sinus arrhythmia (RSA), and the middle frequency band (0.88-0.15 Hz) is attributed to baroreflex components. The low frequency band (0.01-0.08 Hz) may be of various origins, such as blood flow rhythm, periodic respiration (including Cheyne-Stokes respiration), renin angiotensin, and thermal regulation. The efferent nerve to the high frequency band is totally operated by the parasympathetic system. The low frequency band is regulated by both sympathetic and parasympathetic nervous systems. We demonstrated that the diurnal variation of HRV may afford additional information, such as ultradian changes of autonomic activity, possibly due to REM/NREM cycles. It is believed that simultaneous monitoring of other physiological parameters such as EEG, EOG, respiration, and blood pressures, might give us information concerning the dynamic nature of autonomic nervous function. PMID- 1619753 TI - [Diurnal blood pressure variation and autonomic nervous function]. AB - We studied the relationship between diurnal blood pressure variation (DBPV) and autonomic nervous function in various diseases, such as, diabetes mellitus (DM), Parkinson's disease (PD), Shy-Drager syndrome (SDS) and cerebrovascular disease (CVD). Abnormal DBPV was found in those diseases. We speculated that dysfunction of autonomic nervous system might contribute to the abnormal DBPV in DM, CVD, PD, and SDS. The DBPV relates not only to the autonomic nervous system but also the endocrine system, renal function, mental and physical activity, and biological rhythm. From this viewpoint, there is a limitation in studying DBPV as an autonomic nervous function. PMID- 1619752 TI - [The significance and limit of thermography at present]. AB - Thermography has been reported to be usefull in the detection and characterization of nervous diseases. Recently, however, some papers report that it is not useful. In this paper, problems including its history, and measures to solve them are discussed. It is proposed that methods to distinguish patients from normal subjects and information that cannot be obtained by other tests, are needed. PMID- 1619754 TI - [Gastrointestinal motility and autonomic nerve dysfunction]. AB - Gastrointestinal motility is greatly influenced by both the autonomic nervous system (ANS) and the enteric nervous system (ENS). Dysfunction of ANS and/or ENS produces various kinds of dysmotility from the esophagus to the colon. Generalized autonomic dysfunction, often seen in diabetics, causes abnormal peristaltic waves in the esophagus, abnormal electrical activity of the stomach, delayed gastric emptying and delayed intestinal transit. Localized disorders of the enteric nervous system is seen in patients with achalasia and Hirschsprung's diseases. Functional disorders, without evidence of organic disorders, like non cardiac chest pain, non-ulcer dyspepsia, irritable bowel syndrome, can be partly caused by abnormal function of autonomic nervous system. PMID- 1619755 TI - [Tests for autonomic functions: sudomotor function]. AB - Sudomotor function tests provide information on the functional state of the sympathetic system innervating skin, the postganglionic fibers of which are cholinergic. Various methods for sweat elicitation and its qualitative or quantitative detection are described here, but most practical combinations vary depending on the purpose of testing and possible pathophysiology of each patient; 1) hyperhidrosis vs. hypo- or anhidrosis, 2) central vs. peripheral or postganglionic lesions, 3) generalized vs. focal disturbances. When these are unknown, thermal sweating of the whole body is most informative. Comparison of thermal and pharmacological sweating enables one to estimate the extent and possible site of sympathetic disturbance. In evaluating the results of sudomotor function tests, factors due to employed methods, age, sex, posture, medication, etc must be taken into consideration. In general, hyperhidrosis is more difficult than hypohidrosis to estimate its underlying mechanism, since the functional relation between the facilitatory hypothalamo-spinal pathway and other central structures still remains largely unknown. PMID- 1619756 TI - [Sympathetic skin response (SSR)]. AB - The sympathetic skin response (SSR) is a slow wave resulting from activation of the sudomotor sympathetic efferent fibers. Records are usually made with surface electrodes on hand or foot after the electrical stimulation. Either the amplitude or the latency of the response varies greatly on consecutive stimulations and there is also a remarkable tendency to habituation. Therefore SSR is considered abnormal if no significant responses are detected. SSR is well correlated with other autonomic function tests and its abnormality is documented in a variety of neurologic disorders such as diabetic neuropathy, cerebrovascular disease and Parkinson's disease. In good methodological conditions, SSR is a simple, reliable indicator of sympathetic sudomotor outflow in central and peripheral nervous system disorders. PMID- 1619757 TI - [Erectile function and urinary function]. AB - In recent years, with the great advance in neuro-urophysiological concept, the evaluation and limitations of clinical investigation for sexual (erection) function and bladder (urinary) function are continuously changing, so they should be correctly recognized at the time of actual interpretation. The common problems on these functional tests are standardization of terminology and of methodology, and difference of individual sensitivity. From a viewpoint of respective evaluation and limitations, AVSS, NPT, papaverine test, BCR for erectile function tests and CM, UFM, EMG, complex urodynamics for urinary function tests are reviewed. PMID- 1619758 TI - [Clinical application of micro-vibration to autonomic function test]. AB - Microvibration (MV) is the minute vibration observed on surface of the human body. MV on the thenar eminence has been used as an autonomic function test, and is one of the important psychophysiological methods in psychosomatic medicine because the measurement of MV is not invasive. Although the mechanism generating MV has not been definitely clarified, there seems to be two major components, a ballistocardiographic one and a muscular one. The analysis of MV focuses on frequency characteristics. To broaden the clinical application of MV measurement, it is necessary to improve the analyzing method and to develop a way for evaluating MV comprehensively by combining it with other examinations. PMID- 1619759 TI - [Clinical significance of plasma catecholamines in autonomic nerve diseases]. AB - Although it was well known that noradrenaline was secreted from the terminal of sympathetic nervous system, we supposed that plasma noradrenaline does not always indicate sympathetic nervous activity. This was the reason, why we need at least 10 ml of plasma for noradrenaline measurement and so, many plasma sample could not be collect continuously from the same person, 15 years ago. Now, plasma noradrenaline was be analyzed from 0.05 ml of plasma for single isotope radioenzymatic assay. Blood samples of noradrenaline measurements could be collected through venous catheter inserted in cubital vein every 20 min 24 hours. We can study the relationship between circadian rhythm of plasma noradrenaline and that of blood pressure, etc. PMID- 1619761 TI - [Idiopathic orthostatic hypotension (IOH) and sympathotonic orthostatic hypotension (SOH)]. AB - IOH occurs as progressive autonomic failure (PAF) without any neurologic symptoms indicating multiple system atrophy or Parkinson's disease. The responsible lesion for IOH is yet obscure but has been suggested to be in the peripheral sympathetic nerves, since postganglionic sympathetic neurons in IOH fail to release norepinephrine and there present extensive supersensitivities to exogenous pressors. SOH is characterized as marked tachycardia induced by hypotensive stress like standing, and is less sensitive to the administered catecholamines. Careful examinations by some pharmacological studies are essential to diagnose IOH and SOH in patients with orthostatic hypotension. PMID- 1619760 TI - [Shy-Drager syndrome]. AB - Shy-Drager syndrome is characterized by severe orthostatic hypotension and other autonomic dysfunctions, cerebellar ataxia, parkinsonism, and upper and lower motor neuron symptoms. The disease starts in the 4th to 6th decades with severe dizziness, blackout or syncopi on standing up, and the duration of the illness is 6-7 years in the majority of the cases. The pathological lesions responsible for the autonomic dysfunctions are in the hypothalamus, locus saeruleus, Edinger Westphal and other nuclei in the brain stem, intermediolateral column and Onuf's nuclei in the spinal cord. Oppenheimer has postulated a concept of multiple system atrophy to such widely distributed degenerative neurological disorders. However, olivopontocerebellar atrophy of Dejerine and Thomas, striatonigral degeneration and this syndrome can be distinguished clinically as well as pathologically. PMID- 1619762 TI - [Progressive autonomic failure with Parkinson's disease]. AB - Progressive or primary autonomic failure (AF) is a disease of unknown-etiology, and presents generalized and extensive autonomic disturbances because of selective neuronal degeneration in the whole of autonomic nervous system. AF is classified into three categories; (1) pure autonomic failure, without associated neurological disorders, (2) AF with Parkinson's disease (PD), and (3) AF with multiple system atrophy (Shy-Drager syndrome) (Bannister, 1988). AF with PD is pathologically characterized by neuronal cell degeneration in the intermediolateral column and the substantia nigra, together with Lewy bodies mainly in the pigmented nuclei in the brain stem. Patients with PD occasionally develop syncope or dizziness due to orthostatic hypotension and/or postprandial hypotension as well as urorectal disturbances as the initial symptoms, and are followed by parkinsonism. Levodopa is usually effective for parkinsonism but the prognosis is rather poor. AF with PD could be regarded as a form of 'the Lewy body disease' according to Kosaka's clinicopathological entity (1984). PMID- 1619763 TI - [Autonomic dysfunction of central nervous system disorders]. AB - Central nervous system disorders, such as cerebrovascular or spinal cord lesions often cause dysfunctions of the autonomic nervous system. In most cases of acute cerebrovascular accidents, blood pressure is transiently elevated. Some patients, especially with pontine or thalamic hemorrhage, suffer from extremely high fever. In patients with large lesions in the cerebral hemisphere or lesions in the brainstem, cardiopulmonary state may be affected. In spite of absence of acute myocardial infarction, electrocardiogram may show ST-T changes resembling acute myocardial infarction. Cheyne-Stokes respiration or sleep apnea can occur. Lesions in the medulla oblongata cause dysfunctions of automatic respiration. Patients with large cerebrovascular lesions in the unilateral hemisphere often show transient hyperhidrosis on the contralateral side. Prognosis of patients with these autonomic failures is poor. In patients with spinal shock, blood pressure and heart rate are reduced. In chronic stage, autonomic hyperreflexia, such as attacks of episodic hypertension can occur. Lesions in the high cervical cord often bring nonsymptomatic perforating gastric ulcer. PMID- 1619764 TI - [Secondary autonomic diseases--diabetes mellitus]. AB - Diabetic autonomic neuropathy is an established disease entity. Nevertheless, it was not until 1945 that diabetic autonomic neuropathy became a target for extensive systemic research works. This is partly because of insidious progress of this disorder and lack of precise techniques of examinations. In this review article, signs and symptoms of diabetic autonomic disorders characteristic of each visceral organ are described. Among them, such symptoms as painless myocardial infarction and hypoglycemia without warning symptoms deserve special attention. It is essential for clinical doctors to realize that autonomic neuropathy is the most important part for understanding diabetic pathology. PMID- 1619765 TI - [Autonomic dysfunction in metabolic diseases]. AB - Among many metabolic disorders, porphyrias and Fabry disease are known to affect autonomic nervous system. In patients with acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, autonomic symptoms such as abdominal pain, vomiting, hypertension and tachycardia are among the most prominent clinical manifestations. Fabry disease is clinically characterized by severe limb pain, hypohidrosis, angiokeratomas and various autonomic symptoms. In both porphyrias and Fabry disease, pathological changes in the central and peripheral autonomic nervous system have been documented. In porphyrias, a loss of myelinated fibers, axonal degeneration, and segmental demyelination in peripheral autonomic nerves as well as chromatolysis of several brain stem nuclei have been found. In Fabry disease, abnormal amount of the substrates of alpha galactosidase, i.e. ceramide di- and trihexoside, are found to be accumulated in the central and peripheral autonomic nerves. PMID- 1619766 TI - [Autonomic nerve disorders in generalized amyloidosis]. AB - Various autonomic disturbances are usually seen in systemic amyloidosis with polyneuropathy, especially in familial amyloid polyneuropathy (FAP). In this paper we summarized the clinicopathological features of these autonomic symptoms. Orthostatic hypotension and bowel dysfunctions are two major autonomic manifestations of FAP, and at autopsy severe deposition of amyloid is observed in an extensive area of peripheral autonomic nervous system including sympathetic ganglia. Remarkable depletion of the extrinsic nerves with relative preservation of the intrinsic nerves is a characteristic finding in the gastrointestinal tract of the patients with FAP, and this abnormal innervation may produce the peculiar bowel disorders. Oral administration of L-threo-3,4-dihydroxyphenylserine, a precursor of noradrenaline, is effective for the treatment of these autonomic symptoms of FAP patients. PMID- 1619767 TI - [Autoimmune disease among secondary autonomic disease--acute demyelinating polyneuropathy (Guillain-Barre syndrome)]. AB - Acute demyelinating polyneuropathy (Guillain-Barre syndrome) among secondary autonomic diseases was described as a representative disorder due to autoimmune mechanism. The possible roles of preceding vital infection, cellular and/or humoral immune abnormalities in developing the disease have been considered. A comparison was made between acute demyelinating polyneuropathy and experimental allergic neuritis in respects of their causes. Polyneuropathy associated with M proteinemia and Rowland's syndrome was also briefly reviewed. PMID- 1619769 TI - [Riley-Day syndrome (familial dysautonomia)]. AB - Riley-Day syndrome (RDS, familial dysautonomia) is reviewed from a viewpoint of autonomic disturbance. RDS shows pandysautonomia, including alacrima, orthostatic hypotension, gastrointestinal paresis, and paroxysmal hyperautonomic state, such as hypertension, vomiting crisis, and blotchy erythema. Sensory disturbances, including absence of taste and pain sensation, are common. Fungiform papillae on the tongue are sparse. Tests of autonomic function reveal postganglionic dysfunction. Sural nerve biopsy reveals depletion of small myelinated fibers and unmyelinated fibers, which corresponds well with the sensory and autonomic disturbances. As to the pathogenesis of RDS, dysgenesis of neurons from the neural crest or abnormality of nerve growth factor has been suggested, but this remains undetermined. PMID- 1619768 TI - [Abnormalities of autonomic nervous systems in intoxications, including alcohol and drugs]. AB - Disorders in the autonomic nervous system occur frequently in cases with alcoholism or various intoxications. Drugs, especially those related to neurotransmitters may induce complicated symptoms in the sympathetic or parasympathetic nervous system. Some of these symptoms are accompanied by peripheral neuropathy. Intoxication, especially alcoholism is often are combined with a malnutrition, such as avitaminosis. Dysautonomic symptoms change successively; at an early stage, drugs or toxins stimulate sympathetic or parasympathetic receptors, while the same receptors are inhibited at a later stage when the concentration of the substances rises in the blood. Frequent stimulations of the same receptor may produce change in the sensitivity of receptors, decreased metabolism or addiction. These changes suggest that a different approach towards the acute and chronic autonomic disorders caused by intoxications is needed. PMID- 1619770 TI - [Acute autonomic neuropathy and the other related diseases]. AB - In 1969, Young et al. described a patient with an acquired, pure pan-dysautonomia of unknown etiology, involving both the sympathetic and the parasympathetic nervous systems without other neurological manifestations. Since then, a number of similar cases have been described. More recently, reports have appeared of predominantly cholinergic dysautonomia, of dysautonomia associated with infection, and of dysautonomia with other impairment of nervous function. As an etiology, immunological disorder has been suggested but the precise mechanism has not been clarified. By accumulating more cases, a more accurate etiology and more satisfactory therapy will be developed. PMID- 1619771 TI - [Autonomic nerve dysregulation syndrome]. AB - There is no established disease concept to define so-called autonomic dysregulation syndrome. 1) Recently, cases of this disease are being screened by examining autonomic nerve function in patients showing various symptoms that may have been induced by abnormal autonomic nervous system regulation. Based on the test results, dysfunctional cases are classified as autonomic dysregulation syndrome, excluding those cases where dysfunction results from psychiatric diseases, organic diseases of the autonomic nervous system, or endocrinopathy. The disease concept is problematic in that the clinical and pathophysiological condition of the idiopathic and essential autonomic dysregulation syndrome, screened through the above procedure, is unclear. 2) Useful methods are being developed to examine autonomic-nerve function. These methods may provide new materials to establish a concept for autonomic dysregulation syndrome. It is believed that it is time to etiologically classify cases from the standpoint of autonomic nerve dysregulation syndrome. PMID- 1619773 TI - [Localized disturbance of autonomic nervous system--reflex sympathetic dystrophy]. AB - Clinical aspects of the reflex sympathetic dystrophy (RSD) are summarized, along with a review of basic works concerning its pathophysiology. RSD is important not only as a cause of limb pain after trauma and other triggers, but also as a cause aggravating the pain which already has an apparent cause, but is disproportionally severe. PMID- 1619772 TI - [Autonomic facio-cephalalgia]. AB - Autonomic facio-cephalalgia was first described by Brickner et al. in 1935. At that time, it's clinical picture was characterized as pain seizure in the head or face unilaterally with various autonomic signs, such as swelling, redness and hyperthermia of the painful regions. After the first case was described, few cases have been reported, including our two cases. Thus, it's definite clinical entity can not be determined at present. In this review, the history, symptoms, signs, differential diagnosis of this disease and details of two our cases are described. The clinical entity of this disease, on bases of present knowledge is discussed. PMID- 1619774 TI - [Molecular pharmacology of polymorphic arylamine N-acetyltransferase involved in the metabolism of arylamine drugs]. AB - Polymorphic arylamine N-acetyltransferase in the liver determines the N acetylation rate of arylamines, which has been implicated in the effects and toxicity of amine- and hydrazine-containing drugs. Recently we have demonstrated that there are four types of gene for polymorphic N-acetyltransferase and that gene 1 gives rise to high N-acetyltransferase activity, while gene 2, 3, and 4 correspond to low N-acetyltransferase activity. Analysis of four genes revealed that the point mutations in genes 2, 3, and 4 result in a loss of a restriction site: a BamHI site for gene 2, a TaqI site for gene 3, and a KpnI site for gene 4. Therefore all four genes can be discriminated by genomic Southern blot analysis and also by PCR amplification of the respective site followed by digestion with an appropriate endonuclease. PMID- 1619775 TI - [Chronic fatigue syndrome]. AB - Chronic fatigue syndrome (CFS), which is characterized by devastating fatigue, mild fever, lymphadenopathy, headache, myalgia, insomnia and neuropsychiatric disorders, now has drawn much attentions from many physicians, researchers and even peoples in general society world wide. The pathogenesis of CFS is still remains to be clarified and clinico-pathological difference between CFS and mood disorder is controversial. In this paper, CFS would be reviewed in detail. PMID- 1619776 TI - [Structure, function and pathophysiology of mucociliary transport system]. AB - There has been growing appreciation of the significant role played by the mucociliary transport system in the body. The mucociliary transport system is an important defense mechanism by which the human body usually maintains its "homeostasis" by protecting the body against invading particles, including bacteria. This system includes two major functional mechanisms; i.e., ciliary transport and mucous secretional systems, each of which is usually complimentary and cooperative. Three hereditary disorders, primary ciliary dyskinesia (immotile cilia syndrome), cystic fibrosis and Young's syndrome, have been shown to be systemically associated with mucociliary transport failure, leading to male infertility and chronic sinopulmonary infections. Localized mucociliary transport failure, however, is observed in respiratory diseases, especially chronic sinusitis, chronic bronchitis, bronchiectasis and bronchial asthma. We aim, in this review, to draw together those developments in the study of ciliary transport and mucous secretion, the interactions between them and their pathophysiology that can provide a better understanding of the mucociliary transport system of the human body. PMID- 1619777 TI - [The etiopathogenesis of amyotrophic lateral sclerosis--recent development]. AB - In spite of extensive studies of amyotrophic lateral sclerosis (ALS) for the past decades, its cause still remains obscure. Based on the clinicopathological observations and experimental studies of sporadic and endemic ALS cases, etiologic hypothesis encompass a wide range of postulated pathophysiological mechanisms in the various fields. Reviewing briefly these, recent concern on genetic hypothesis, of familial ALS, background of case aggregation in the Western Pacific and immune hypothesis has been discussed. Although there is no unifying theory explanatory for ALS process at present, accumulated results through basic and clinical neurological science may provide a better understanding for the pathogenesis of ALS. PMID- 1619778 TI - [Neuro-immunomodulation]. AB - Recent evidence has provided information that the immune system can be activated by non-antigenic stimulus e.g. stress. Information on the bidirectional communication between the neuronal and immune systems has been growing, while increasing evidence suggests that neuromodulators, released from the neuronal systems, influence the immune cells. Conversely, the activated immune cells release an array of immunomodulators that influence the physiologic function of the nervous system. An attempt was made to restore the altered immune function following exposure to stress by the treatment of the olfactory system with various fragrances. From the data in experimentally designed mouse models, it was found that the individual sensitivity to the fragrances was restricted by the genetic background (H-2) of the mice. The adaptation to the fragrances with regard to the recovery of the immune response to stress, was also characterized. The ability of the adaptation to the fragrances was found to differ not only due to the genetic background of the mice but also different fragrances. PMID- 1619779 TI - Bladder reconstruction with ileum after cystoprostatectomy for bladder cancer: analysis of the micturition and continence of 44 consecutive patients. AB - From October, 1987, to August, 1990, 47 patients underwent an ileal low pressure bladder replacement using the Hautmann procedure after radical cystoprostatectomy for bladder cancer. The qualities of micturition and continence were evaluated from a questionnaire mailed to the patients and by urodynamic examinations in 44 consecutive patients over a follow-up period of more than 3 (mean 10.7) months. The 44 patients (100%) were perfectly dry during the daytime and voided every 4 (2-6) h with a micturitional volume of 357 (200-500) ml. Forty-two of the 44 patients had no residual urine. Thirty-three of the 44 patients (75%) were perfectly dry at night with a voiding frequency of 1.5 (0-3). Seven of the 44 patients (16%) were occasionally incontinent (spotting less than 2/week). Four of the 44 patients (9%) had night incontinence and used as external device. Only two patients showed high pressure waves of greater than 50 cm H2O. The maximum urethral pressure was 59.07 +/- 13.6 (30-80) cm H2O. The maximum flow rate was 17.2 +/- 9.7 (4.5-35) ml/sec. The different factors responsible for the new micturitional balance were discussed. With its very good functional results and its ease of performance, the ileal neobladder is, for us, the procedure of choice for bladder reconstruction after cystectomy. PMID- 1619780 TI - Skull base malignant lymphoma: a case report and review of the literature. AB - A case of primary malignant lymphoma of the skull base is reported. A 62-year-old man was admitted with headache and diplopia. Computed tomography and magnetic resonance imaging showed an abnormal mass in the right parasellar region. The final diagnosis after surgery was primary malignant lymphoma of the skull base. Primary malignant lymphomas sometimes occur in the central nervous system but those in the skull base are exceptional. The present paper presents just such a rare case of malignant lymphoma of the skull base. Diagnosis and combined therapy consisting of surgery, radiotherapy and chemotherapy for the disease are discussed, and the literature on recent clinical problems of central nervous system lymphomas is reviewed. PMID- 1619781 TI - Early extramedullary plasmacytoma confined to the lamina propria of the gastric mucosa: case report. AB - A case of early gastric plasmacytoma in a 51-year-old woman is reported. The demonstration of monotypic IgM-kappa immunoglobulin in biopsy specimens by an immunoperoxidase technique contributed to the histological diagnosis. The patient had non-ulcerative lesions (of approximately 15 x 16 cm) of a superficially spreading type of gastric plasmacytoma. Extensive histological analysis of the resected stomach showed the IgM-kappa monoclonal proliferation of plasmacytic tumor cells to infiltrate merely into the lamina propria of the gastric mucosa and not to extend deeply into the submucosa, proper muscle and serosa of the stomach. PMID- 1619782 TI - Effect of Krestin (PSK) on the induction of IL-2 activated killer cells. AB - The effects of Krestin (PSK) on the generation of lymphokine-activated killer (LAK) cells were examined in tumor-bearing mice. BALB/c mice were inoculated subcutaneously with methylcholanthrene-induced fibrosarcoma (Meth A) cells, and PSK was administered intraperitoneally every other day. The reduced LAK activity in tumor-bearing mice was restored by the administration of PSK. Since involvement of the humoral immunosuppressive factor in the impairment of LAK activity has been suggested, the effect of PSK on the impaired LAK activity in the presence of an immunosuppressive factor isolated from the ascites of X5563 (plasmacytoma)-inoculated mice was examined. The activity reduced by the immunosuppressive factor in an in vitro induction of LAK was restored by incubation with PSK. The antimetastatic effect of IL-2 was also augmented by its combined use with PSK. The data provide a rational basis for using PSK in combination with recombinant IL-2 in cancer immunotherapy. PMID- 1619783 TI - Carcinoid tumor of the lung: clinicopathological study of 32 cases. AB - A retrospective study was conducted on 32 patients who had had bronchial carcinoid tumors between 1965 and 1989. The average age of the patients was 48.5 years, with a male to female ratio of 3.6:1. Of the 32 patients, 28 were diagnosed pathologically to have typical bronchial carcinoid tumors and the other four, atypical bronchial carcinoid tumors. Twenty-two of the 28 typical bronchial carcinoid tumors were classified as stage I, but only one of the four atypical bronchial carcinoid tumors was at stage I. Two typical carcinoid tumor patients and two atypical carcinoid tumor patients were found, pathologically, to have lymph node metastasis. The typical carcinoid tumors showed a more significant endobronchial polypoid growth than the atypical carcinoid tumors (P = 0.0138). The five-year-survival rate was 100% in patients with typical carcinoid tumors and 25% in those with atypical carcinoid tumors. The difference between the five year-survival rate for the typical carcinoid and atypical carcinoid patients was statistically significant (P = 0.001). PMID- 1619784 TI - An evaluation of serum microelement concentrations in lung cancer and matched non cancer patients to determine the risk of developing lung cancer: a preliminary study. AB - In a case-control study to determine the risk of developing lung cancer, the serum levels of vitamins A and E, carotene and selenium were determined in 31 patients, newly diagnosed as having lung cancer, and in matched controls, the said controls being selected from outpatients with no cancer. A significant, inverse association was found between serum vitamins A and E and lung cancer. The relative risk for the low vs high tertiles were, respectively, 5.94 for serum vitamin A and 8.44 for serum vitamin E. Taking histological cancer subtype into account, no relation was revealed between the microelements and squamous cell carcinoma of the lung. The relative risk for lung cancer was 6.50, however, when three, or all four, microelement levels were in the lowest tertile, compared with there being fewer than three in the lowest tertile. Even when three microelements, excluding vitamin E which had the most significant inverse association with lung cancer, were considered, the relative risk was 7.50 when any two or all three were in the lowest tertile, compared with there being just one microelement or none at all in the lowest tertile. A combined effect of vitamins A and E, carotene and selenium on the development of lung cancer has, therefore, been suggested. Further studies will thus be necessary to elucidate the cumulative effect of the serum micronutrients and trace elements, as well as the effect of single elements, on the development of lung cancer. PMID- 1619785 TI - [Effects of external systemic irradiation on changes in immunoreactivity of radiolabeled monoclonal antibody]. AB - Effects of external systemic irradiation on changes of immunoreactivity by radiolabeled monoclonal antibody administrated intravenously to the nude mice were pursued with the method of cell binding assay in vitro. Enhancement of tumor localization and biodistribution of radiolabeled antibody following systemic irradiation were performed in tumor bearing mice. Results obtained were as follows: 1) Immunoreactivity of monoclonal antibody administrated to the nude mice showed the tendency of a gradual fall in comparison with that of pre administrated. While there found to be no changes of immunoreactivity preserved 37 degrees C in vitro. 2) Systemic irradiation could prevent immunoreactivity of post-administrated antibody from falling gradually, and there found to be dependent upon a dose of irradiation. 3) In an animal model tumor localized activity was significantly made higher than in the not irradiated control group dependent upon a dose of irradiation and tumor to tissue ratio was in the same way. 4) These results indicated that external systemic irradiation for tumor bearing mice would also be beneficial for practical use and clinical application of radiolabeled monoclonal antibodies, besides contributed to the improvement of systemic irradiation-bone marrow transplantation therapy. PMID- 1619786 TI - [Attempt to cause hepatitis in duck hepatitis B virus carrier ducks by immunization with DHBV protein]. AB - In order to investigate the hypothesis that viral hepatitis is a host immune response against viral protein presented on hepatocytes, we attempted to cause hepatitis in DHBV carrier ducks by immunization with DHBV protein. While ducks injected with Freund Complete Adjuvant (FCA) showed only weak hepatitis, those immunized with DHBV particle protein showed severe hepatitis. This same procedure could not cause significant inflammation in the liver of ducks without DHBV infection. The severity of hepatitis was well associated with the frequency of the immunization. However, the degree of hepatitis activity was different among same times immunized ducks. Occurrence of hepatitis assumed to have close association with host immune response against viral protein. PMID- 1619787 TI - [Morphological comparison between pm-carcinoma and minute ss-carcinoma of the gallbladder]. AB - Eleven cases of pm-carcinoma and thirty cases of minute ss-carcinoma of the gallbladder were compared with their morphologies and biological behavior with reference to the assessment of pm-carcinoma as early carcinoma. The vascular permeation and lymph nodal metastasis was 9% and 0%, respectively, in the pm carcinoma and 43% and 9% in the minute ss-carcinoma. The 5-year survival rate of the pm-carcinoma was better (100%) than the minute ss-carcinoma (73.3%). The poorly differentiated adenocarcinoma or well differentiated adenocarcinoma with high grade atypia in the invasive-area was higher in incidence in the minute ss carcinoma. From these findings it is concluded that the pm-carcinoma should be defined as early carcinoma in the gallbladder. The both carcinomas were hardly distinguishable macroscopically. Therefore, the careful examination of resected gallbladder by stepwise sections is important. PMID- 1619788 TI - [Relationship between juxtapapillary duodenal diverticula and biliopancreatic disease--evaluation by endoscopic biliary manometry]. AB - Endoscopic biliary manometry was performed to evaluate the motor activity of the sphincter of Oddi (SO) in 28 patients, 13 with juxtapapillary duodenal diverticula (8 with biliopancreatic disease) and 15 without diverticula (10 with biliopancreatic disease). So pressure and the rate of irregular wave pattern of phasic contraction in patients with diverticula were significantly higher than those in patients without diverticula. Especially all the patients with both diverticula and biliary stones had motor disorders of the SO. The patients with diverticula were also divided into three groups by endoscopic findings for the location of diverticular; The papilla of Vater was located close to diverticula (within about 4 cm) in group A, on the edge of diverticula in group B, in the diverticula in group C. Diverticula could have more direct effect on the motor activity of the SO in group C. Those results suggest juxtapapillary diverticula have close relationship with the motor activity of the SO and biliopancreatic disease, especially in cases which the papilla of Vater located in the diverticula. We conclude that the motor disorders of the SO might be responsible for biliopancreatic disease in patients with juxtapapillary diverticula. PMID- 1619789 TI - [Microspectrophotometric analysis of DNA content in duct epithelial proliferation and invasive carcinoma of the pancreas]. AB - Nuclear DNA content of 131 pancreatic duct epithelial lesions, including 10 normal ducts, 30 intraductal proliferations with mild atypia (groups I-II), 30 with moderate atypia (group III), 24 with severe atypia (group IV), 14 of carcinoma in situ (group V), and 23 invasive carcinomas, was analyzed using microspectrophotometry. DNA histograms were classified into diploid, polyploid and aneuploid patterns. All of normal duct epithelia showed diploidy. Polyploid patterns were observed in 3 (10%) lesions of groups I-II, 17 (56.7%) of group III, 14 (58.4%) of group IV, 7 (50%) of group V, and 6 (26.1%) of invasive carcinomas, and aneuploid patterns were observed in 0%, 10%, 33.3%, 50% and 73.9%, respectively. This distribution of ploidy patterns revealed a gradual shift to the main ploidy from diploid to polyploid followed by aneuploid in proportion to the increase of the degree of epithelial atypia. The frequencies of polyploid cells in each lesion were determined. Their averages were 0.2% in groups I-II, 1.9% in group III, 3.4% in group IV, 4.4% in group V, and 6.7% in invasive carcinoma. The S+G2M phase fractions were significantly higher in proliferative epithelia than in normal. The results of this study suggest that duct epithelial proliferations of the pancreas have "genetic instability" leading to a serial clonal evolution and play a significant role in the progression of pancreatic duct cell carcinoma. PMID- 1619790 TI - [A case report of drug-resistant gastric ulcer caused by celiac axis compression syndrome]. PMID- 1619791 TI - [A case of malakoplakia of the colon]. PMID- 1619792 TI - [A case of hepatic angiomyolipoma mimicking a small liver cancer]. PMID- 1619793 TI - [A case of splenic malignant lymphoma with severe liver dysfunction]. PMID- 1619794 TI - [Percutaneous anterior approach under ultrasonic guidance for the celiac plexus block]. PMID- 1619795 TI - [Coexistence of foreign worker and industrial health]. PMID- 1619796 TI - [Health effects of non-occupational exposure to asbestos]. AB - Mesothelioma has occurred in a relative large number not only among miners but also among non-occupationally exposed persons living in the northwestern region of Cape State of South Africa, where crocidolite is mined and transported. The long-term residents of Thetford Mines in Quebec Province, Canada, who have never engaged in mining and milling of chrysolite have not shown an excess mortality of respiratory diseases. Tremolite in soil is responsible for mesothelioma among residents of certain geologic regions such as Cyprus, Corcica, northwestern Greece and Turkey. An increased prevalence of malignant mesothelioma has been reported among residents of three Turkish villages due to exposure to erionite fibers having a high carcinogenic potency. Mesothelioma has infrequently developed in wives who were exposed while washing the work clothes of their husbands contaminated with asbestos, especially amphiboles. The levels of airborne asbestos in public buildings and schools in the U.S.A. and England having walls and ceilings constructed with asbestos containing materials are approximately 1/100 of the permissible concentration of 0.2 f/cm3. The estimated risk from asbestos exposure in schools and buildings is lower than the level of other risks in other society. During the work of removing asbestos from buildings the asbestos concentration is remarkably increased and this persists for many weeks thereafter. The level of asbestos fibers released from brake linings of motor vehicles is higher along roads with heavy traffic, at intersections, and near toll booths than elsewhere. The concentration of asbestos fibers released from motor vehicles is generally low and not of the level to induce mesothelioma. PMID- 1619797 TI - [Development of posture measuring apparatus using goniometer and inclinometer. 2. Fixation, precision and calibration of goniometer]. AB - A new posture measuring apparatus was developed for time and motion study in the field of industrial health. This apparatus records working postures by measuring angles of joints and trunk inclination. The angles of joints were measured by the newly developed goniometers which use the bending loss of rubber optical fibers. This paper presents results of studies made on the fixation, precision and calibration of goniometers which are important in the actual application of this apparatus. Six freedoms of five joints were examined, i.e. elbow (flexion/extension), shoulder (abduction/adduction and horizontal adduction/abduction), hip (flexion/extension), knee (flexion/extension), ankle (dorsi-flexion/plantar-flexion). The results obtained were as follows; 1) Goniometers should be fixed according to the characteristics of each joint. 2) The output errors were calculated from the measured data, excluding the effects of flexed angles, subjects and fixations. The mean output error of all joints was 0.189 V (14.3 degree). 3) The output errors by the three calibration methods using logistic curves were calculated. The output errors for 2-point method (calibrated by the data of minimum and maximum angles) and 3-point method (calibrated by the data of minimum, medium and maximum angles) were 1.34 and 1.22 times larger than the output errors (0.139 V) for all-point method (calibrated by all measured data), respectively. PMID- 1619798 TI - [Studies on fatigue and shift work in nurses]. AB - Effects of shift work on physiological parameters and autonomic nervous-adrenal system were studied on six hospital nurses. Their body temperature, heart rate, blood pressure, fluctuation in ECG R-R intervals, serum catecholamines and cortisol, and subjective fatigue ratings before and after day, evening and night shift were determined. Furthermore, mean heart rates, walk steps, estimated energy expenditure, and urinary catecholamine excretion were determined three times for eight hours each during each shift work day. The following results were obtained: 1) No significant changes were detected in the physiological parameters before and after each shift work, except for elevation in plasma adrenaline level after night shift. 2) Heart rate, blood pressure and subjective fatigue rating tended to be higher, though not significantly, at the beginning of night shift, when compared with the data obtained on the some time of day, i.e., at the end of evening shift. 3) On the other hand, the plasma cortisol level tended to be suppressed after night shift, suggesting that even one night shift work may change the circadian rhythm of plasma cortisol. 4) Statistical analyses showed that in contrast to day and evening shift, in night shift there was no significant positive correlation between eight-hour walk steps, and eight-hour mean heart rate and urinary adrenaline excretion, suggesting an altered circadian rhythm in heart rate and urinary adrenaline excretion and also a possible additional psychological load in night shift. These results suggest that even one night shift work could modulate the autonomic nervous-adrenal activity of hospital nurses, compared with day or evening shift, and indicate that it is necessary to lengthen the time interval before and after night shift work. PMID- 1619799 TI - [Determination of protoporphyrins in blood using HPLC. Standardization of protoporphyrins and interlaboratory comparison of analyses]. AB - 1) In order to compare the results of determination of protoporphyrin IX (PP) and zinc protoporphyrin IX (ZP) using HPLC, the preparation procedures for standard solutions of PP and ZP were studied at four laboratories. According to the methods mutually agreeable to the four laboratories, the absorption values using UV-Vis spectrometer from the 4 laboratories were found to be identical. 2) The total of 28 whole blood samples obtained from the same workers whose Pb-B levels ranged from 2.9 to 87.9 micrograms/dl were sent to the 4 laboratories for determination of PP and ZP. The laboratories were allowed to use their own HPLC apparatus, column, mobile phase and fluorometric detectors, although the same procedures were used to prepare the standard solutions of PP and ZP. The results showed that significant biases in ZP and PP levels were found between two out of the 4 laboratories, but the ZP values corrected by the recovery rate showed no statistical difference among the laboratories. 3) Blood levels of ZP, total protoporphyrin (TP, calculated by PP+ZP/1.1), and PP determined by HPLC method correlated well with free erythrocyte protoporphyrin (FEP) determined by the method of extraction into the acidic solvent. The correlation coefficients between Pb-B and log TP, ZP, FEP or PP were 0.82-0.84, 0.80-0.83, 0.786, or 0.70 0.73, respectively. 4) The coincident ratios of PP/TP obtained at 4 laboratories ranged from 12.1 to 19.0%. These values were within a relatively narrow range, although two different kinds of organic solvents (DMF: N',N'-dimethylformamide or Methanol/triton-X 100) were used in the extraction steps.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619800 TI - [Determination of acetone, methanol, and methyl ethyl ketone in urine using head space gas chromatography (HS.GC)]. AB - Using HS.GC, We have succeeded in simultaneous determination of Ac, MeOH and MEK in urine without any complicated pretreatment or correction by internal standard. Moreover, in order to lower the detection limits of these materials, study was made on the salting out effect using 14 kinds of salts. As pretreatment, 2.0 ml of urine, 3.0 g of sodium sulfate and small sized magnetic stirrer are put into vial, which is sealed by septum. This is then heated for 10 min in warm bath of 50 degrees C. In order to dissolve the added salts as much as possible, the specimen is stirred by the stirrer. After cooling the liquid to room temperature, the specimen is analysed by HS.GC. The results showed that sodium sulfate was excellent synthetically. 1) Using the urine of workers not exposed to organic solvents three kinds of urine having specific gravity of 1.010, 1.024 and 1.034 were prepared and mixed standard organic solvents (Ac, MeOH and MEK) were added. Recovery percentages and coefficients of variation were calculated. The results showed that recovery percentages ranged from 92.0 to 101.7% and coefficients of variation from 0.2 to 4.6%. 2) The regression equations of standard curves were satisfactory with y = 9053x - 200(r = 0.999, n = 12) for Ac, y = 801x - 400 (r = 0.999, n = 12) for MeOH, and y = 15488x - 277 (r = 0.999, n = 12) for MEK. 3) The detection limits calculated by IUPAC formula were 0.0092 mg/l for Ac, 0.11 mg/l for MeOH and 0.0063 mg/l for MEK. These results indicated that this method is superior to other methods because the pretreatment is very simple, specificity is excellent, analysis by standard curves is possible, and this method is not affected by specific gravity of the urine. PMID- 1619801 TI - [Fatigue symptoms and their related factors of workers in institutions for the mentally retarded]. AB - This study examined the fatigue symptoms and their relative factors in a group of nursery teachers and guidance workers (n = 480) belonging to institutions for the mentally retarded. 1) More than 50% of the respondents complained of neck stiffness and/or backache. The mean scores of the physical symptoms were higher than the standard cumulative fatigue symptoms index, while those of the mental symptoms were lower. 2) Analysis of variance showed that physical fatigue symptoms were higher in females, younger workers, those with longer years of service, those with more night duties per month, and those who expressed more dissatisfaction with their co-workers, wages, working hours, and work shift. Physical fatigue symptoms were not related to the severity of the mental disease of their clients. 3) Analysis of variance also showed that mental fatigue symptoms were higher in females, younger workers, and persons who expressed more dissatisfaction with their jobs, supervisors, co-workers, wages, working hours, and work shift. The severity of the mental disease of their clients was directly related to the mental fatigue symptoms. Furthermore, multiple classification analysis showed that those working with children had both higher irritability and morale than those working with adults. PMID- 1619802 TI - [Recovery study from anemia and alterations of glutathione metabolism in erythrocytes induced by chronic inhalation of ethylene oxide]. AB - A study was made on the recovery from anemia induced by chronic exposure of ethylene oxide. When rats were exposed to ethylene oxide at a concentration of 500 ppm, 6 h a day, 3 d a week for 13 wk, macrocytic normochromic anemia with a high reticulocyte count was observed. The hematological values were also evaluated 4 and 13 wk after the end of exposure and the values were found to have already recovered at 4 wk. We reported previously that anemia induced by ethylene oxide was accompanied with a decrease in glutathione reductase activity and instability of glutathione. In this study, alterations of glutathione redox cycle after the end of exposure were examined. The recovery in the decrease of glutathione reductase was slow and the speed of recovery seemed to be dependent on the life span of erythrocytes of the rats. The decrease in glutathione content completely recovered at 4 wk after the exposure. It was concluded from these observations that anemia induced by ethylene oxide is reversible. PMID- 1619803 TI - [Nondestructive synchrotron radiation X-ray fluorescence imaging of trace elements in human kidney tumours]. PMID- 1619804 TI - [Self-judged work activity level and nutritional intake in 30-year-old males]. PMID- 1619805 TI - [Effect of seasonal and intermittent work at high altitude on health status]. AB - Health status of 7 men was examined in order to study the effect of duty work cycle of 3-d stay at the altitude of 2,000 m and one-day holiday at 600 m for a period of 6 months from May to October. Their usual works were desk work and road patrol. Total hemoglobin concentration in blood increased significantly after work at high altitude, which was considered to be a compensatory response to the hypoxic state. Subjective symptoms were obtained by a self-administered questionnaire before (April), during (June and October) and after (November) work at high altitude. Fatigue was observed in three out of the seven subjects in June, which subsequently disappeared in October. Dyspnea was observed also in June in three of the subjects, which disappeared in two, persisted in one, and newly appeared in another subject in November. In contrast, a tendency of favorable effects of the work environment on nausea and lumbago was observed. Blood pressure and pulse rate were measured for 24 h. The mean systolic blood pressure during 24 h decreased in two of five subjects in October and November, and the mean values during the working hours decreased in two in October from 145 to 131 mmHg and from 147 to 129 mmHg, respectively. The blood pressure measured at health examination correlated well with the mean blood pressure during 24 h and working hours. The mean pulse rate during 24 h and working hours increased in one in June, October and November. These results indicate that adaptive responses to low barometric pressure environment developed during a work period of 5 months at high altitude.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619806 TI - Radioimmunoassays for melatonin using an antiserum raised against a novel antigen. AB - The highly specific antiserum to melatonin (MT) was produced, and the sensitivity and specificity of the radioimmunoassays (RIAs) using this antiserum was investigated. An immunogen was synthesized by binding 6-hydroxy-melatonin (6-OH MT) to bovine serum albumin with a spacer of 6-bromohexanoic acid ethyl ester. Rabbits were immunized subcutaneously once a month with 1.0 mg of the immunogen for 7 months. The antiserum was characterized by a crossreactivity test by RIA using 125I-labelled MT. The antiserum specifically recognized MT but hardly did other analogues except for 6-OH-MT with a crossreactivity of only 0.4%. Two RIAs were established using [o-methyl-3H]MT and 2-[125I]iodo MT. In both RIAs, inhibition curves for MT were obtained in the range of 10 pg to 10 ng and 1-2 ng of MT inhibited the value of the assay at "0" by half. The similarity of the RIAs in sensitivity and inhibition by unlabelled MT is discussed on the basis of the structures of radioactive MTs and that of the immunogen. PMID- 1619807 TI - The use of mass fragmentography for the detection of tetrodotoxin in human body fluids. AB - The authors report on a convenient electron impact ionization-mass fragmentographic method for determining the amount of tetrodotoxin (TTX) present in body fluids. To explain this method briefly, the TTX present in body fluids was purified with activated charcoal and transformed into 2-amino-6-hydroxymethyl 8-quinazoline (C9-base) with alcoholic KOH (1%). Then the C9-base was injected into a gas chromatograph-mass spectrometer in the form of trimethylsilyl derivative. In this manner the minimum detectable amount of TTX in body fluids was found to be about 0.01 microgram/g. When this method was applied to sera, urine, and the stomach contents of 2 decedents suspected of puffer fish poisoning, 0.053 microgram/g of TTX was detected in stomach contents of one victim. This new analytic method is simpler and more sensitive than other assay methods and thus is considered useful in forensic work. PMID- 1619808 TI - The effect of cyanide on isolated perfused rat heart. AB - Using Langendorff isolated perfused rat hearts, we demonstrated direct effects of cyanide on the heart. A heart from a sacrificed male rat was placed on a Langendorff apparatus and perfused with Tyrode solution containing 2.0 mM NaCN (CN-TS), following with normal Tyrode solution (TS) at 37 degrees C. During perfusion we monitored the heart beat, and the state of inorganic phosphate (Pi), creatine phosphate (CrP) and adenosine triphosphate (ATP) by 31P-NMR spectrometer equipped with a surface coil probe. After the beginning of the CN-TS perfusion, the heart was initially excited, and ceased beating completely seventy seconds later. During CN-TS perfusion, the CrP immediately disappeared, but the ATP level was maintained considerably. The peak of Pi shifted to the right, indicating acidosis in the heart. These results suggest that the ATP level in a heart during exposure of cyanide is maintained by activation of anaerobic glycolysis in compensation for cellular oxygen utilization. PMID- 1619809 TI - Teratogenic effects of methamphetamine in mice. AB - Eight-day pregnant Jcl:ICR mice were administered methamphetamine hydrochloride i.p. at doses of 11, 13, 14, 15, 17, 19 and 21 mg/kg. The number of animals that died after the treatment increased dose-dependently. The highest maternal mortality rate (50%) was observed in the 21 mg/kg group. On day 18 of gestation, the animals were killed and fetuses were examined for external and skeletal malformations. The mortality and malformation rates of fetuses increased with the increase in dose, but both rates reached their highest levels at a dose of 19 mg/kg. Exencephaly, open eyelids, cleft palate and rib anomaly were frequently observed malformations. The single teratogenic dose was estimated to be 19 mg/kg for both external and skeletal malformations. This amount was about ten times the daily intake of many Japanese abusers. The risk of malformed infants being born to female abusers was considered to be high. More crowded conditions have been reported to increase the fetal malformation rate. The higher malformation rate in the 19 mg/kg group than in the 21 mg/kg group was considered to be due to fewer surviving mice in the 21 mg/kg group, because of a higher mortality rate. PMID- 1619811 TI - [Morphometric and pathologic studies of the brain in autopsied cases of Alzheimer type dementia]. AB - Human brain sections were analysed by computer-assisted quantitative morphometry. The brains, autopsied at the Department of Legal Medicine, Kobe University School of Medicine and the Medical Examiner's Office of Hyogo Prefecture, included 63 cases of acute death consisting of 49 cases of non-demented and 14 cases of Alzheimer's disease (AD) or senile dementia of Alzheimer-type (SDAT). As for patients of AD and SDAT, they were clinically diagnosed at some medical facilities in their life time. Histopathological diagnosis for AD and SDAT was confirmed by the presence of abundant senile plaques and neurofibrillary tangles. In the non-demented control aging, a modest atrophy occurred throughout the cerebral cortex except the occipital cortex, whereas no sign of atrophy was seen in the medullary white matter. In the AD and SDAT cases, both cortical gray and medullary white matter showed significantly higher degrees of atrophy than in the controls. A further detailed study indicated that the parietotemporal association cortex was specifically affected in the demented brain as compared with the normal aging. PMID- 1619810 TI - [The effect of a p-phenylenediamine containing hair dye on the Ca2+ mobilization in the chemically skinned skeletal muscle of the rat]. AB - In order to clarify the mechanism of a p-phenylenediamine (PPD)-related occurrence of rhabdomyolysis, the pharmacological effects of PPD, a main component of hair dyes, on the function of the contractile proteins and the sarcoplasmic reticulum (SR) have been investigated in single skeletal muscle fibers of the rat by using the skinned fiber method. The results of our findings are enumerated below 1) A positive contraction of the skinned fibers by the PPD, and a complete suppression of the contraction by Mg2+, and a negative contraction by caffeine while under conditions with 50 mM of PPD were noted, suggesting that the contraction of the muscle by PPD is caused by the release of Ca2+ from the SR. 2) PPD inhibited the Ca2+ uptake by the SR in a concentration-dependent manner. 3) PPD greatly accelerated Ca2+ leakage from the SR, and the number of Ca2+ remnants 3 minutes after the administration of 50 mM of PPD amounted to only 3%. 4) The calcium-induced calcium release (CICR) was accelerated in areas with a low Ca2+ concentration, and the amount of Ca2+ released at a pCa of 7.5 showed an increase of up to 63% on PPD administration of 50 mM. 5) PPD did not influence the Ca2+ sensitivity of the contractile system. It thus has been speculated that PPD can bring about rhabdomyolysis by promoting the CICR and leakage of Ca2+ from the SR, this being followed by an increase in the Ca2+ concentration and by consequent changes that develop in the muscle, such as continuous contraction, an irreversible change in the muscle's structure and/or a hypermetabolic change. PMID- 1619812 TI - [A case of death due to neurogenic shock]. AB - An autopsy case of death due probably to neurogenic shock (primary shock) is reported. A 14-year-old boy got into a fight with his elder brother and received blows against the chest and abdomen. The young boy fell down senseless on the floor and had a spasm. An ambulance was called, but he was dead on arrival at a hospital. An autopsy revealed no external injuries on the chest and abdomen. There was no evidence of preexisting disease. On histological examination, there were signs of acute cardiac failure; edema of the lungs, liver and gall bladder, partial myofibrillar degeneration and cytoplasmic vacuoles in the media of a small coronary artery. Thus, the autopsy did not give any explanation of the fatality. It seems probable, however, that the blow(s) against the abdomen (the solar plexus) caused a fatal shock (vagal inhibition). In addition, the adrenal cortices (especially the zona fasciculata) were narrowed and the aorta was slightly narrow in caliber. It is likely that these hypoplasia might affect the fatal shock consequent to very slight injuries. PMID- 1619813 TI - [Laryngeal fractures due presumably to tracheal intubation in resuscitation]. AB - In three autopsy cases performed in our department, we observed the throat skeleton fractures occurring presumably during the tracheal intubation in resuscitation. Case 1. 63-year-old man died of acute hemorrhagic pancreatitis shortly after the quarrel with a suspected person. The autopsy examination showed the fractured hyoid bone with haemorrhage at the fracture site. The question whether direct pressure on his neck by the suspected person results the fracture of the hyoid bone was investigated. Case 2. 75-year-old man treated for senile dementia was clubbed with a walking stick by the other patient treated for same disease and he died of traumatic shock. The fracture of the hyoid bone was also noted like case 1. The strike in the throat and/or the neck compression by the assailant were suspected of being the cause of this fracture. Case 3. 47-year-old man got the severe head injury during the quarrel. He died about two weeks after operation and the cause of death was multiple organ failure. The autopsy findings revealed the fracture of the superior thyroid horn. The neck compression by the suspected person was the questionable cause of this fracture. In all these cases, the asphyxia findings and the signs of the direct pressure on the neck by the assailants were not recognized other than the above-mentioned laryngeal fractures. From the autopsy findings, together with the criminal investigation, we consider collectively that the tracheal intubation in resuscitation induced presumably these laryngeal injuries. In general, throat-skeleton fractures seem to be the signs of homicidal violence against the neck.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619814 TI - [The results and problems of reoperation for coronary artery disease]. AB - In six hundred and six consecutive patients undergoing coronary artery bypass grafting (CABG) within the past 17 years (May 1974 to March 1991), repeated CABG were performed on 10 patients (1.65%). The main reasons for repeated CABG were graft failure (GF) in 8, progression of native disease (NP) in 5 and incomplete revascularization (IR) in 3 patients. The incidence of GF was high either within a half year or around 5 years after CABG. Although all patients survived from reoperation, four patients continued to have mild angina pectoris. When the recurrence of angina is noted after CABG, coronary arteriography and if necessary PTCA should be done as soon as possible. If a second surgery is inevitable, maximum utilization of arterial graft and accomplishment of complete revascularization are emphasized. PMID- 1619815 TI - [Clinical study of paragangliomas in the thorax]. AB - Four cases of paraganglioma in the thorax, consisted of 3 cases originating from the mediastinum and a case of pulmonary metastasis from the posterior peritoneum, were clinically investigated. Three were malignant and one was benign with noradrenaline secretion. On surgical excision, preoperative arterial embolization was assumed to be useful for reducing hemorrhage during procedure. Pre and intra operative circulatory management was also mandatory in case of functioning paraganglioma. Of the 3 malignant cases, 2 survived for more than 10 years with radiotherapy alone or surgical resection of multiple metastatic nodules in the bilateral lungs. The other one, though inoperable due to extensive invasion to right and left atria, showed highly sensitivity to intra-arterial infusion chemotherapy of CDDP. These results suggested that long term survival might be expected even in metastatic or inoperable cases. There were no reliable histologic features distinguishing malignant from benign tumors, however 2 malignant cases with local invasion showed aneuploid patterns in the DNA histograms, which might offer a adjunct possibility in the assessment of malignancy. PMID- 1619816 TI - [Surgical treatment of active infective endocarditis and prosthetic valve endocarditis]. AB - Fifteen patients with active native valve endocarditis (NVE) and 5 with prosthetic valve endocarditis (PVE) were subjected to this study. Among the patients with NVE, one of 10 with simple destruction of leaflets and 2 of 5 with annular infection died postoperatively of cerebral bleeding and persistent infection. Five patients with annular infection, whose microorganisms were Streptococcus faecalis, Staphylococcus epidermidis and gram-negative coccus, had a shorter duration from onset to operation (mean 38 days) compared with the others (mean 85 days). A patient with NVE requires an urgent operation, especially when these microorganisms are identified. Among those with PVE, 3 underwent operation at the active phase and one at the chronic phase. Two patients with mechanical valve endocarditis by Staphylococcus and Candida died, but the other 2 with bioprosthetic valve endocarditis by alpha-Streptococcus survived, because infection was localized in the leaflets. Another patient with mechanical valve endocarditis by alpha-Streptococcus survived with conservative management. While a patient with bioprosthetic valve endocarditis requires an early operation as well as NVE, a patient with mechanical valve endocarditis requires selected management considering the microorganism and general condition. PMID- 1619817 TI - [Method to make the tricuspid extracardiac conduit by heterogeneous pericardium]. AB - We described here, how to make tricuspid extracardiac conduit by heterogeneous pericardium for Rastelli procedure. We have developed some ingenious devices which allow to obtain good hemodynamics. One of the devices is large valvular leaflets as long as 130% of the circumference of the conduit. Another device is the commissural suture as figure of eight. We used 121 tricuspid extracardiac conduits between January 1985 and March 1991. There were two reoperations: One from stenosis at the suture with ventricle and the other from infective endocarditis. This hand-made conduit has the advantages of flexibility, fitness with the pulmonary artery, wide range of size and very little regurgitation. These advantages indicate that the tricuspid extracardiac conduit made by heterogeneous pericardium is a valved conduit substitute of choice for Rastelli procedure. The durability of the conduit is to be further evaluated. PMID- 1619818 TI - [Congenital lobar emphysema successfully treated by right upper lobectomy at five hours after delivery: a case report]. AB - Lobar emphysema is a rare disease and one of the causes of respiratory disturbance in the newborn and infancy. A case report is presented and compared with related data in the literature in Japan. Maternal echographic findings indicated the cystic lung disease of the fetus. The cystic space was punctured and aspirated three times. The baby was delivered by caesarean section after having taken sufficient precaution to prevent respiratory failure. Since the baby developed dyspnea gradually, at five hours following the delivery, right upper lobectomy was performed and the major symptoms were eliminated. The pathological diagnosis was congenital lobar emphysema and the etiology was concluded to be bronchiectasis. PMID- 1619819 TI - [Surgery versus detachable balloon embolization of pulmonary arteriovenous fistula: clinical experience]. AB - We experienced 4 pulmonary arteriovenous fistula cases 2 of which were treated surgically and 2 were subjected to detachable balloon embolization therapy. Favorable results were obtained in the detachable balloon embolization therapy. In treating pulmonary arteriovenous fistula, if the lesion is in the position where the catheter can be reached easily and is composed of a single afferent efferent vessel unit, it would be advisable to perform the embolization therapy first, and then to apply an operative procedure preserving lung tissue as much as possible. PMID- 1619820 TI - [Closure of median sternotomy incision with EPTFE sutures]. AB - EPTFE (CV-0) suture was utilized for closure of median sternotomy incision in 100 patients under 6 years of age who underwent open heart surgery. During 3 years follow up, except for one dislocation of sternum, all patients have healed without complication. EPTFE suture is swanged to a needle that has the same diameter as the thread, which reduces bleeding from the needle hole. It is radiologically lucent, and therefore does not disrupt chest X-ray, angiography or MRI investigations, in contrast to sternal wires. In addition, in the case of life threatening postoperative complication, EPTFE suture allows rapid and simple access to the heart, without the need to cut wires. We concluded that EPTFE suture can be utilized for closure of median sternotomy in patients under the age of six, without an increased risk of postoperative or long-term complications. PMID- 1619821 TI - [Delayed sternal closure; a simple sternal splint]. AB - A simple and inexpensive sternal splint for delayed sternal closure was described. Sternal edges were splinted open using an edge-cut disposable syringe. This method has been employed successfully in 10 patients (one adult, 9 children). This syringe splint is a simple, inexpensive and effective method for delayed sternal closure. PMID- 1619822 TI - [Repair of two cases of partial anomalous pulmonary venous return by draining total right pulmonary venous blood to the left atrium through dilated atrial septal defect]. AB - Two cases of partial anomalous pulmonary venous return were reported in whom right pulmonary veins were totally drained to the coronary sinus and to the right atrium respectively. Re-routing of pulmonary veins was done by dilated atrial septal defect and making intra-atrial tunnel using equine pericardial patch. Postoperative courses were uneventful. MRI was useful to identify the pathway from right pulmonary veins to the left atrium. PMID- 1619823 TI - [Two cases of atrial septal defect with absence of right superior vena cava and persistent left superior vena cava]. AB - Two women (16-year-old, 54-year-old) of atrial septal defect with absence of right superior vena cava and persistent left superior vena cava were successfully operated on. Electrocardiographic findings show coronary sinus rhythm and atrial fibrillation. When we closed atrial septal defect cannulated to persistent left superior vena cava via the coronary sinus directly, sick sinus syndrome was not appeared postoperatively. PMID- 1619824 TI - [Clinical analysis of 6 cases of pericardial cysts]. AB - We present a clinical analysis of 6 cases of pericardial cysts. There were two males and four females. Only one case of them had complaint of persistent cough. Four of 6 were observed in right costo-phrenic angle, and 2 were in left costo phrenic angle. Surgical excision was performed in 6 cases, and all patients recovered good health. We suggest that in cases of pericardial cysts, surgical treatment should be performed, even if patients would not have remarkable complaint. PMID- 1619825 TI - [A case report: Rastelli operation for double outlet right ventricle associated with a chordae insertion to the infundibular septum]. AB - A successful Rastelli operation for double outlet right ventricle (DORV) with a chordae insertion of the tricuspid valve to the infundibular septum was reported. A patient was a 6-year-old boy and the diagnosis was DORV, d-malposition of the aorta and pulmonary stenosis. The infundibular septum was not resected but mobilized with two incision, one anterior and vertical, and other one subaortic. This procedure allowed the construction of the tunnel similar to the closure of a large, subarterial VSD and of the straight unobstractive left outflow tract. The postoperative echocardiographic and angiographic examination revealed neither the pressure gradient in the left ventricular outflow tract nor the tricuspid regurgitation. PMID- 1619827 TI - [A successful resection of recurrent right ventricular myxoma]. AB - A successful surgical treatment of right ventricular myxoma of twenty-year-old male was presented, who healed already previous resection of left atrial myxoma two year and eight months prior to this operation. He has been followed up closely after the first resection of left atrial myxoma for the recurrence in the left atrium. Follow-up echocardiography demonstrated the development of myxoma in the free wall in the right ventricle. The resection for this myxoma was found to be relatively easy at the second operation. The tumor was removed with the stark, without any postoperative problem. According to the literature, this case seems to be the second Japanese case of surgical treatment of right ventricular myxoma following the removal of left atrial myxoma. PMID- 1619826 TI - [Successfully treated intraoperative coronary artery spasm in a patient with type B dissecting aortic aneurysm: a case report]. AB - A 65-year-old man with chronic type B dissecting aortic aneurysm, complicated by variant from of angina pectoris without any coronary artery obstructed disease on preoperative angiogram was operated upon through left posterolateral thoracotomy under the left heart bypass with Bio-pump system using preoperative Ca antagonists and intraoperative nitroglycerin infusion. Shortly before the end of operation the patient suddenly developed shock status definitely due to coronary artery spasm, associated with ST-elevation in II, III, aVF and bradycardia, then ventricular tachycardia, finally cardiac arrest. The patient was resuscitated by cardiac massage and administration of nifedipine and nitroglycerin. Such attacks repeated five times at ten or twenty minutes intervals. The coronary artery spasm could be successfully suppressed with the additive use of noradrenaline infusion. The patient had no attacks at all postoperatively and was discharged with good success. This case suggests that the prevention of intraoperative coronary artery spasm is essential, but if it occurs, additive use of noradrenaline infusion is effective for the cessation of coronary artery spasm. PMID- 1619828 TI - [A case report of thoracic ectopia cordis]. AB - Complete type of thoracic ectopia cordis was diagnosed with prenatal ultrasound study. Just after birth of female baby with 2,750 g body weight, a silastic mesh was selected for covering the heart because of no space for putting the heart into the mediastinum. Protrusion of the liver towards the mediastinum was one of main causes of lifting the heart outside the chest wall. The baby died 7 days after her birth due to heart failure. Soft silastic mesh was not good enough to sustain the ectopic heart constantly and caused paradoxical respiratory movement of mediastinal side of the lung. It is concluded that hard shell coverage of the extremely ectopic heart is necessary to sustain it constantly and to prevent paradoxical respiratory movement of mediastinal side of the lung. PMID- 1619829 TI - [A surgically treated case of acute pulmonary embolism owing to deep vein thrombosis of the leg mainly caused by uterine myoma]. AB - A 49-year-old woman with deep vein thrombosis of the left leg suddenly complained of slight dyspnea during her hospitalization. Enhanced chest CT and pulmonary arterial DSA revealed pulmonary emboli, while phlebography of the left leg and lower abdominal CT showed a uterine myoma compressing the left external iliac vein, which was regarded as a chief cause of deep vein thrombosis of the left leg. The patient became dyspneic severely with a rapid increase of pulmonary arterial pressure and a decrease of arterial oxygen pressure. Therefore, pulmonary embolectomy and deep vein thrombectomy of the left leg and pelvis was performed using a cardiopulmonary bypass. Hysterectomy was also performed after weaning the bypass. The postoperative course was uneventful without recurrence of pulmonary embolism. This was a very rare case of pulmonary embolism, because, as far as we investigated, no literature has reported deep vein thrombosis of the leg caused by uterine myoma. We emphasize the availability of the enhanced CT for diagnosis of pulmonary embolism. PMID- 1619830 TI - [A case of acute extrinsic malfunction of prosthetic valve due to suture tag causing incomplete closure of the disc]. AB - A 56-year-old woman who had suffered from both aortic and mitral valve stenosis and regurgitation was treated by replacement of valves with 23 mm and 27 mm Bjork Shiley valves respectively. After weaning from cardiopulmonary bypass, the arterial systolic pressure rose to 100 mmHg but the diastolic pressure fell to 40 to 50 mmHg. Studies including transesophageal echocardiogram and fluoroscopy during operation revealed the valves functioning normally. Because low diastolic pressure and low cardiac output continued during postoperative period, fluoroscopy was carried out again. It showed incomplete diastolic closure of the disc of the prosthetic aortic valve. The emergency operation was performed. At reoperation, it was found that one of the end of suture knots located between the valve ring and the disc prevented the occluder from seating completely and caused aortic regurgitation. The suture end was cut shorter and the prosthesis within the sewing ring was rotated so that the occluder was kept away from the suture end. PMID- 1619832 TI - [Functional pulmonary atresia: a case report]. AB - A male neonate, two days of age, was admitted with cyanosis and tachypnea. Chest roentgenograms showed massive cardiomegaly and decreased pulmonary vasculatures. Echocardiographic and the right ventriculographic findings were interpreted as showing primary pulmonary atresia with secondary tricuspid incompetence. At a Brock operation, however, there was no resistance in passing the instrument through the pulmonary valve. The baby died twelve hours after surgery. Postmortem examination showed that the tricuspid regurgitation was a cause of the functional pulmonary atresia (FPA). It is important to distinguish FPA from pure pulmonary atresia because conservative therapy is the first choice for the FPA. PMID- 1619831 TI - [A case of extra-anatomic bypass for ruptured thoracoabdominal aortic aneurysm with tuberculosis]. AB - Now aneurysmectomy and graft replacement is the most popular surgical method of aortic aneurysm, but there are many opinions about surgical methods and assist circulation for emergency operation of ruptured aortic aneurysm. We experienced the case of ruptured thoracoabdominal aortic aneurysm with tuberculosis, and rescued the patient by extra-anatomic bypass (EAB). A 60-year-old woman, who had been treated with tuberculosis for about 40 years, was operated on for cold abscess of her left psoas muscle by other orthopedic surgeons. At that time, massive bleeding happened, and she was transferred to us under diagnosis of ruptured thoracoabdominal aortic aneurysm. EAB, as emergency operation, was done because we considered it was dirty and dangerous to replace the prosthesis beside the abscess. The postoperative course was almost uneventful except the evidence of Gaffky's first stage. We considered EAB was an useful method for emergency cases and some infectious aortic aneurysms. PMID- 1619833 TI - [A case of coronary artery bypass for bilateral coronary ostial stenosis in aortitis syndrome with occlusion of bilateral subclavian arteries]. AB - A 52-year-old female with bilateral coronary ostial stenosis in aortitis syndrome underwent CABG. Vein grafts were used instead of arterial grafts, because of the occlusion of bilateral subclavian arteries. Proximal anastomosis of the grafts was performed after oval stomas larger than usual were created on the aortic wall to prevent late graft occlusion due to intimal proliferation of the aorta. On postoperative CAG, all grafts to RCA, LAD and Cx were patent. The patient left the hospital 3 weeks after surgery. We believe that CABG is preferable to the transaortic endarterectomy in the surgical treatment for coronary ostial stenosis associated with aortitis syndrome, because of the prevalence of technical difficulty and postoperative morbidity in the latter. PMID- 1619834 TI - Chief complaints. PMID- 1619835 TI - Pending lawsuits and judgment liens. PMID- 1619836 TI - Cooperation is key to solving health-care woes, she says. Governor Joan Finney. PMID- 1619837 TI - Women physicians increase their numbers and their clout. Not for men only. PMID- 1619838 TI - Intra-abdominal lymphangioma. AB - Intra-abdominal lymphangiomas are rare occurrences. Of the few cases reported, most are in infants or young children. This case was in a 13-year-old boy with no previous history of problems. The etiology is probably a primary malformation of the lymphatics, which may cause blockage or inflammatory responses and subsequent enlargement of the lymphatic channels. Clinically, the patient presents with features typical of a space-occupying lesion, as in this case. This patient presented with symptoms of an obstruction or pressure from the growing mass. In diagnosis, a sonogram or CT scan is helpful. The recommended treatment is complete excision, if possible. PMID- 1619839 TI - True composite lymphoma: non-Hodgkin's lymphoma and Hodgkin's disease. PMID- 1619840 TI - The cardiovascular risk of general anesthesia. PMID- 1619841 TI - [Initial steps in the aid project of Mother-Child-Development in Mtwara]. PMID- 1619842 TI - [Modern intensive care for the prevention of infant mortality]. PMID- 1619843 TI - [Soder Hospital--a good alternative]. PMID- 1619844 TI - [Pain--a quality of life in parturient women]. PMID- 1619845 TI - [Is hormone contraception a time bomb?]. PMID- 1619847 TI - Katilo ammatinharjoittajana [the profession of midwifery. PMID- 1619846 TI - [The hormone diaphragm affords safe contraception and relief from menstrual pain]. PMID- 1619848 TI - [Introduction to the Pirkanmaa Midwifery College and its curriculum]. PMID- 1619849 TI - Investigational methodologies for the effects of brain maturation on energy transport. AB - Intracellular kinetics of high energy phosphate (HEP) is of fundamental importance in cellular biochemical physiology. In mammalian brain, intracellular HEP transport from the production site (mitochondria) to the consumption site (plasma membrane) is dependent on passive diffusion of HEP through the cytosol. Diffusivity of a substrate in a solution correlates inversely to the viscosity of the solution. The maturational process of mammalian brain involves dramatic changes in the cytosolic amino acid profile. Since the viscosity of a solution is a function of the diffusion coefficients of solutes and their concentrations, changes in the cytosolic amino acid composition should result in significant alteration in cytosol viscosity and hence, HEP diffusivity. Such a system is especially suitable for mathematical modeling and correlative analysis by in vivo nuclear magnetic resonance (NMR) spectroscopy. This brief review is written to provide a fundamental background for investigational methodologies on developmental neurobiology of cellular energetics. PMID- 1619850 TI - Control of constitutively-expressed developmentally-activated rat hepatic cytochrome P450 genes. AB - Cytochromes P450 (P450) collectively refer to a superfamily of heme-containing enzymes that use O2 and electrons from NADPH to insert a single atom of oxygen into any one of a large number of substrates. Two general classes of P450s exist; a relatively limited number of P450 forms, expressed in specialized tissues that are associated with pathways of steroidogenesis and a large number of forms responsible for metabolism of foreign compounds. Most of the latter P450s are expressed in liver, the primary site for metabolism of drugs, unusual dietary compounds and environmental pollutants. Numerous forms of P450 are expressed in liver of untreated animals and these are regulated quite differently. Both developmentally-programmed and sex-specific expressions have been observed. In this review, I will summarize recent findings on the mechanisms by which two P450 genes are regulated in livers of developing rats. The CYP2E1 gene is transcriptionally activated within a few hours after birth while the CYP2C6 gene is activated just prior to rats reaching puberty. These genes are under control of two transcription factors, HNF-1 alpha and DBP, respectively, that themselves are developmentally controlled. PMID- 1619851 TI - Usefulness of hemilaminectomy for microsurgical management of intraspinal lesions. AB - Hemilaminectomy is a limited, unilateral approach to the spinal cord that provides excellent exposure of the dorsolateral and ventral portions of the spinal canal. This approach is most suitable for microsurgical management of the majority of extramedullary tumors. Contrary to conventional laminectomy, the posterior supporting structures of the spine are completely preserved on the contralateral side with this access route. The procedure has been applied in 3 patients who harbored a cervical neurilemmoma, a cervical lipoma, and a thoracic neurilemmoma, respectively. Optimal exposure of the lesion was achieved in each case, and each patient's symptoms improved or completely resolved postoperatively. There were no surgical complications. It is concluded that hemilaminectomy combined with microsurgical techniques should be given priority over standard laminectomy in the surgical management of extramedullary lesions arising in the spinal canal. PMID- 1619852 TI - Detection of H-ras gene point mutations in transitional cell carcinoma of human urinary bladder using polymerase chain reaction. AB - It has been reported that the H-ras gene is activated as oncogene in human bladder cancer cases, and that codon 12 and codon 61 are the major "hot spots" of its activation. A simple method to detect point mutations in these codons of H ras gene was established for the use of clinical diagnosis. In this method, the DNA segments including codon 12 or codon 61 were amplified by polymerase chain reaction (PCR), and the reaction products were examined for their susceptibility to the restriction enzyme NaeI or BstNI, and by dot blot hybridization assay with oligonucleotide probes. Point mutations were detectable in small amounts of DNAs isolated from fresh or frozen tumor tissues, urine cells and paraffin sections. The method was applied for a clinical sample and a case that had a point mutation at codon 12 of H-ras gene was detected. The point mutation was existed in DNAs of primary tumor tissue, all recurrent tumor tissues and cells isolated from urine of this case. PMID- 1619853 TI - Deficits of problem-solving ability in patients with focal brain damage: neuropsychological investigation of prediction and hypothesis behavior. AB - Deficits of problem-solving ability in focal brain-damaged patients, with special reference to frontal lobe dysfunction, were investigated by two neuropsychological tests: Temporal rule induction test and Hypothesis-testing measure. Subjects consisted of 84 chronic brain-damaged patients (31 with anterior cerebral lesions and 53 with posterior lesions). The study's aim was to investigate the effects of frontal lobe damage on two aspects of inductive reasoning, prediction and hypothesis behavior. When prediction was examined by Temporal rule induction test, patients with anterior lesions showed deficits in predicting a rule, even in the memory-aid condition in which memory factors were excluded. The poor results on Temporal rule induction test in frontal patients did not appear to be related to deficits in temporal integration, which is generally interpreted as frontal dysfunction. Rule induction may be impaired by frontal damage whenever complicated information-processing is required, even when temporal succession is not involved. Second, two stages of hypothesis behavior, hypothesis-formation and hypothesis-testing, were evaluated. Patients with anterior lesions showed impairment in hypothesis-formation. Their decreased fluency in hypothesis production affected the hypothesis-testing process. However, frontal patients committed fewer errors, most of which were perseverative (lose-stay errors) on hypothesis-testing. Patients with posterior lesions revealed other characteristic errors, such as inconsistent responses and divergent-type errors (improper lose-shift errors). The hemispheric site of the lesion affected only the ability to maintain a hypothesis (win-shift errors). The results illustrated the differences in problem-solving deficits in these two groups of patients. Disturbed prediction of future events, decreased hypothesis fluency, and abnormal lose-stay behavior in patients with frontal lobe damage may be crucial factors in coping with daily problem-solving situations. PMID- 1619854 TI - Acute hepatic failure in a 49-year-old man succeeding to a surgery for malignant thymoma. PMID- 1619855 TI - [Use of antiprotein donor plasma for specific detoxication therapy of children with severe burns]. AB - Antiproteic donor plasma was included into the complex of treatment of 54 severely burned children, who had their clinical state, immunologic and hematologic indices been studied. A pronounced therapeutic effect of antiproteic immunotherapy was noted. PMID- 1619856 TI - [The effect of antiprotein plasma on humoral resistance in children with severe burns]. AB - In severely burned children, depending on severity of injury, the anti-triptic activity of blood serum, alpha 2-macroglobulin level, fibronectin, activity of an arginase decrease at the acute period of toxemia and septic toxemia. The content of the products of fibrin-fibrinogen degradation increases considerably. Alteration of the indices studied is of informative value and is associated with dynamics of the toxic syndrome development. Use of donor antiproteic plasma has a positive therapeutic effect. PMID- 1619857 TI - [Bleeding from acute gastric and intestinal ulcers in surgical treatment of cholecystitis]. AB - The experience with treatment of 33 patients who developed hemorrhage from acute ulcers of the alimentary canal at the early period after cholecystectomy has been analysed. The clinical, biochemical and instrumental criteria of likelihood of the development of such a complication have been established. The methods for its prevention and treatment with the use of the techniques developed by the authors, which permitted to reduce the incidence of this complication from 13.7 to 6.9%, are described. PMID- 1619858 TI - [State, effectiveness and improvement of the quality of care for burn patients]. AB - The data on the incidence of burns in Ukraine, provision with a specialized hospital stock, level of specialized aid, terms of transfer of the burned patients from the central district hospital, central city hospital, specific weight of the operative interventions performed for thermal injuries, general operative activity, lethality both of the adults and children with burns are presented. The ways for improving the quality of a specialized aid are outlined, new techniques of skin plasty operations are suggested. Particular attention is given to quality of rendering help in central district hospital, central city hospital. The ways for reduction of lethality in burns are shown. The importance of conservative and operative rehabilitation of burn convalescents, possibility of essential enhancing their social and vocational rehabilitation are stressed. PMID- 1619859 TI - [Experimental and clinical foundation of the effectiveness of the use of an extracorporeal "auxiliary liver"]. AB - For extracorporeal detoxication in treatment of experimental burn disease and hepatic failure in patients, the dispersed hepatic tissue was used. Restoration of the processes of biotransformation and detoxication, normalization of content of different metabolites, decrease in activity of transaminases, improvement of general state of the patients were noted. PMID- 1619860 TI - [Prediction of bleeding from esophageal and gastric varices in patients with liver cirrhosis]. AB - A course of the disease was studied in 190 patients with hepatic cirrhosis and portal hypertension without bleeding as well as in 107 patients with bleeding from esophageal and gastric varices. The Wald's consecutive analysis with derivation of a summary diagnostic coefficient on the basis of 13 clinical signs was used. Effectiveness of the method was assessed by means of retrospective analysis of 150 case records and long-term results of treatment of 30 patients. The method permits to predict the development of gastroesophageal bleeding in 95.4% of cases. PMID- 1619861 TI - [Use of therapeutic discrete plasmapheresis in combination with extracorporeal blood irradiation with ultraviolet rays in the treatment of patients with obliterative disease of blood vessels of the lower extremities]. AB - The results of treatment of 440 patients with obliterative diseases of the arteries of the lower extremities are presented. Use of the ultra-violet rays for extracorporeal irradiation of the blood in combination with discrete plasmapheresis has a pronounced therapeutic effect, contributes to improvement in regional blood flow and shortening the duration of patients' staying in the hospital by 5-7 days. PMID- 1619862 TI - [Microwave therapy of frostbite of the extremities]. AB - In the experiment, frostbite of the hind legs in rabbits was induced for 3 hours. The extremities of 12 animals of the experimental group were influenced with UHF field with a wavelength of 12.6 cm of nonthermal intensity (3 W) for 10 minutes one time after termination of cold influence. The extremities of 18 rabbits of the control group were warmed in a natural way. The milder course of cold trauma in animals of the experimental group manifesting itself in higher temperature of a skin of the damaged extremity, more rapid disappearance of edema and lesser spreading of cyanosis, tissue necrosis of an extremity--(7.6 +/- 2.5) and (11.7 +/- 1.2) cm, respectively--was noted. The authors consider that microwave therapy can be included into the complex of measures at the early period of treatment of local cold trauma. PMID- 1619863 TI - [A method for improvement of blood circulation in composite grafts in the preventive and reconstructive surgery of burns]. AB - In 58 patients after performance of plasty with fatty-cutaneous and fasciocutaneous grafts, the state of circulation in the flaps was studied. The level of ischemic disorders was defined. The medicamentous complexes contributing to improvement of circulation in the grafts are suggested. PMID- 1619864 TI - [Specifics of dermotensive skin reconstruction in children]. AB - The technique of dermotension, peculiarities and expediency of its use in postburn and mechanical skin deformation in 50 children ranging in age from 2 to 14 years are described. It is expedient to perform operative elimination of the postburn alopecia, severe contracture of the neck, cicatricial bandage of the chest and abdomen by means of the dermotensive flaps. This permits to reduce a number of operative steps, create a sufficient reserve of healthy tissue identical to the lost one both in texture and in colour. Dermotension has the advantages over the pediculate plasty and can be widely used in children with the burn sequelae. PMID- 1619865 TI - [Specifics of wound healing in patients with extremely severe burns as effected by various methods of treatment]. AB - Peculiarities of the course of a wound process in 52 patients ranging in age from 16 to 60 years with the extremely severe burns were studied. Suppression of the vascular reaction and deceleration of the cellular reactions of the extravascular phases of inflammation, alteration of protease-antiprotease activity at the region of injury in dynamics of a wound process were revealed. Antiinflammatory action of the combined methods of general and local sorptive detoxication were substantiated. Certain mechanisms of increase in anti-infective resistance of the organism of the sufferers were elucidated. PMID- 1619866 TI - [The use of protease inhibitors in the treatment of burn wounds]. AB - The results of experimental and clinical studies of the effect of contrykal and aminocaproic acid on tissue regeneration in deep burns are presented. In the experiment, by means of planimetric, histologic, histochemical and biochemical methods of investigation, the positive effect of inhibitors on healing of the burn wounds is shown. In treatment of 272 patients with deep burns, it was established that use of protease inhibitors at the phase of regeneration contributed to 2-fold acceleration of marginal epithelization, shortening of time of would preparation to autodermoplasty by 3-4 days, increase in effectiveness of survival of the cutaneous flaps. A possibility of wide clinical use of proteolysis inhibitors predominantly in combination with antibiotics is shown. PMID- 1619867 TI - [Early surgical treatment of deep burns]. AB - Twenty four patients with deep burns were treated. Survival of free transplants was noted in excision of the necrotic tissues to fascia. An unsatisfactory result of plasty was noted in perifocal inflammation and leaving a necrotized crust along the periphery. In use of mesh transplants with an enlargement coefficient 1:2, the optimal survival was achieved. PMID- 1619868 TI - [Immunocorrective therapy of patients with mandibular fractures]. AB - The authors have summarized their experience with local use of lysozyme in the treatment of patients with mandibular fractures. PMID- 1619869 TI - [The use of helium-neon laser radiation in the treatment of trophic disorders in patients with diabetes mellitus]. AB - The effectiveness of laser therapy in trophic skin disorders (ulcer, diabetic bulla, hematoma, skin chap) in patients with diabetes mellitus was studied. The foci of trophic disorders and biologically active points were irradiated by means of heliumneon laser installations. The technique was employed in a hospital and in out-patient treatment in the complex with medicamentous therapy and without that in patients resistant to medicamentous therapy. A high effectiveness of laser therapy has been established. PMID- 1619870 TI - [Treatment of purulent-necrotic diseases in patients with diabetes mellitus]. AB - The experience with treatment of 214 patients suffering from diabetic angiopathy complicated by purulent-necrotic tissue lesion, which included intraarterial administration of antibiotics, insulin, novocaine, vasodilators, antiaggregants, anticoagulants, vitamins, is summarized. In soft tissue necrosis, gangrene of the toes, or foot, the necrotized tissues were excised, exarticulation, or amputation of toes, metatarsals, in extreme cases, amputation of a leg at the thigh level, were performed. PMID- 1619871 TI - [Relaparotomy after appendectomy]. AB - A result of 70 relaparotomies performed after the operative intervention for acute appendicitis has been analysed. The causes and indications for reoperation, an outcome, nature of complications which required performance of relaparotomy have been considered. A classification of relaparotomies depending on time of their performance is suggested. PMID- 1619872 TI - [Isoniazid content of lungs in patients with pulmonary tuberculosis depending on the method of its administration as part of a comprehensive preoperative preparation]. AB - Isoniazid concentration in the resected areas of a lung was studied in 47 patients with tuberculosis. It has been proved that galvanization of the chest against the background of intermittent intravenous chemotherapy allows to create a high concentration of the preparation in the damaged part of a lung situated at the interelectrode space. Isoniazid content in the wall of the caverna and paracavernous tissues in patients after the direct current influencing was (5.3 +/- 1.0) and (15.2 +/- 1.2) mukg/g. These indices were significantly higher than in patients, who sustained enteral, or intravenous drip administration of the preparation 3 times a week. Intravenous intermittent chemotherapy in combination with galvanization is indicated at the time of preoperative preparation of the patients. PMID- 1619873 TI - [Diagnosis and surgical treatment of complicated acute cholecystitis in elderly and very old patients]. PMID- 1619874 TI - [Free bodies of the abdominal cavity]. PMID- 1619876 TI - [A method for tying a double knot]. PMID- 1619877 TI - [The surgical needle]. PMID- 1619875 TI - [Preparation of porcine spleen for splenosorption in children]. PMID- 1619878 TI - [A method for surgical treatment of pathologic mobility of the kidney]. PMID- 1619879 TI - [Multiple recurring necrosis of skin resulting from radiation therapy]. PMID- 1619880 TI - [Treatment of a child with burns complicated by sepsis and gastrointestinal bleeding]. PMID- 1619881 TI - [Free transfer of the latissimus dorsi flap to sites with decompensated regional blood flow in burn and vascular surgery]. AB - In the experiment, a sluggish wound of an extremity against the background of chronic ischemia was modelled in white rats. Then, a scapular muscle was transferred onto a wound defect. Free transfer of the latissimus dorsi flap (LDF) aimed at closure of the extensive wound defect and revascularization of the tissue ischemia area was performed in 29 patients: for high-voltage electric burn (12 cases), frostbite (5), radiation ulcer (4) and obliterative diseases of the lower extremities (8). Complications--partial, or total necrosis of a flap- occurred in 11 patients. Risk of free LDF transfer is justified because of absence of the other methods for prevention of amputation of the extremities. PMID- 1619882 TI - [Prediction of the severity of the course of a pathologic process at various stages of burns using phytolectins]. AB - To predict the course of a pathological process in burn patients, the possibility for using the agglutinative capacity of erythrocytes caused by presence of lectins in the aqueous-saline extracts of the 12 species of drug plants permitted for use in medicine was studied. The activity of lectins was judged about by the intensity of agglutination of erythrocytes in 21 donor and in 26 patients with III-IV degree burns at different stages of the disease. A significant decrease in total agglutinative activity of erythrocytes in burn convalescents as compared with that in healthy patients was established. PMID- 1619883 TI - Comparison between natural and immunized anti-GM1 antibodies analyzed by marker releasing rate assay with liposome. AB - Naturally occurring rabbit anti-GM1 was compared with immunized induced anti-GM1 antibody in the same individual rabbits by the characterization of immune potency determined by complement-dependent damage to liposomes containing GM1 as antigen. Antigen-antibody reaction was the rate determining step in this assay. The maximum rate was measured by the first derivative conversion monitoring in spectrophotometry and the maximum level of marker released was measured by the conventional method described previously. When the concentration of sera required to get fifty percent of maximum values in each assay were compared, the ratios (rate assay/conventional assay) were 5.7 to 10.0 in natural antibodies and 3.2 to 2.3 in immunized induced antibodies, respectively. Furthermore, the maximum rate of marker release from liposome was not correlated with the maximum level of marker released depended on the sources of antibodies. These results suggest that natural antibody, even the titer was high in conventional liposome assay, has different characteristics compared with the immunized induced antibody. PMID- 1619884 TI - Massive gastric cancer in a patient with a negative Gregory antigen (Gy (a-)), a rare blood group. AB - A case of a massive advanced gastric cancer of the Borrmann type III in a patient with the rare blood group of negative Gregory antigen (Gregory (a-)) is reported. On admission, he was found to have a severe anemia (Hb 6.1 g/dl) requiring a direct blood infusion. He had never received a blood infusion, previously. In blood crossmatching tests, his blood was agglutinated by all the antisera for the common antigens, and he was discovered to have a rare blood type of Gregory (a-). There was no appropriate blood donor in his family. Before the operation, only 600 ml (6 i.u.) of frozen red blood cells could be found in storage from only 2 people with Gregory (a-), O blood type and Rh (+) in Japan. To increase the RBC, erythropoietin (3000 i.u.) was administered 6 times; and the Hb increased to 7.4 g/dl. However, the anemia remained and 200 ml (2 i.u.) Gregory (a-) blood was infused, preoperatively. The final preoperative Hb was 7.8 g/dl and the RBC was 283 x 10(4)/mm3. A massive gastric cancer directly infiltrated the pancreas, the transverse colon and the mesocolon. A palliative subtotal gastrectomy with combined resection of the transverse colon was performed. The intraoperative blood loss was 460 ml and the volume of blood infused was 400 ml (4 i.u.). The postoperative Hb was 7.9 g/dl, and more blood was needed. However, there was no more Gregory (a-) donor blood in storage in Japan.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619885 TI - Anomalous multifocal ossification of the os calcis--case report. AB - A three-month-old female baby was diagnosed by roentgenograms as having bilateral multifocal ossification of the os calcis. Five ossification centers in the bilateral calcaneus were recognized. However, at one year of age the roentgenograms showed only three ossification centers, with cleft separating on both sides the anterior third from the posterior two-thirds of the bone. At two years of age, the three ossification centers had coalesced into a single composite ossification center and the cleft at the calcaneus disappeared. PMID- 1619886 TI - Modified De Vega's annuloplasty for functional tricuspid regurgitation--early and late results. AB - From 1978 through 1987, 321 patients who had functional tricuspid regurgitation (TR) associated with mitral or combined mitral and aortic valve disease underwent tricuspid annuloplasty with our modification of the original De Vega's annuloplasty technique. The modified De Vega's annuloplasty consisted of two separate semicircular sutures placed around the anterior and lateral aspect of the tricuspid valve. Preoperatively, 229 (71.3%) of the 321 patients were in New York Heart Association functional class III or IV. There were nineteen early deaths (5.9%), and 15 patients died during a follow-up period of 15 to 126 months (mean follow-up, 26 months). Five patients (1.5%) required reoperation because of biological mitral valve failure and recurrence of mitral stenosis. The severity of TR was evaluated by two-dimensional and pulsed Doppler echocardiography, and was classified on a scale of 0 to Grade 3 according to the maximal distance and the flow pattern of the regurgitant signals in the right atrium. Postoperative echocardiographic evaluation of TR was performed in 121 randomly selected patients late after operation. TR reduced to Grade 1 or less in 107 (88.4%) of the 121 patients after operation. Ninety-six percent of the survivors were in New York Heart Association functional class I or II, postoperatively. The actuarial survival rate for the 321 patients with the modified De Vega's annuloplasty including early deaths was 88.2% at 10 years and the actuarial rate of freedom from reoperation on the tricuspid valve was 97.6%. Our surgical experience indicated that the modified De Vega's annuloplasty, as the method of first choice, is a simple, reliable procedure and resulted in reduction of the severity of TR in 88.4% of the patients with functional TR. PMID- 1619887 TI - Surface charge of fractionated guinea pig keratinocytes measured by free-flow cell electrophoresis. AB - Keratinocytes differentiate from basal cells to spinous, granular, and horny layer cells. It is known that alterations in the surface charge of cell membranes in most cases reflect the processes of differentiation. By using a continuous colloidal silica (Percoll) density gradient, keratinocytes may be separated into three fractions which correspond to their arrangement in vivo. Using a free-flow cell electrophoretic technique, we measured the electrophoretic mobility of guinea pig keratinocytes. Electrophoretic mobility histograms of basal and granular cells showed slow and fast monophasic patterns, respectively. In spinous cells, a biphasic pattern of slow and fast electrophoretic mobility was present. The electrophoretic mobility level of guinea pig keratinocytes was slightly reduced with neuraminidase digestion. Those of human red blood cells and lymphocytes, however, were markedly decreased. These results indicate that membrane charge density is lower in basal cells and higher in granular cells and that the membrane charge density of guinea pig keratinocytes involves not only neuraminic acid residues but also other substance(s). Our results illustrate the alterations of cell membrane charge properties during epidermal cell differentiation. PMID- 1619888 TI - Clinicopathologic study of perineural invasion in rectal cancer. AB - Perineural invasion (PNI) in rectal cancer was studied, prospectively. One hundred patients (20%) were identified as having tumors with PNI. The incidence of PNI was significantly increased in tumors with moderate or marked venous invasion (30%, 64%), with moderate or marked lymphatic permeation (37%, 72%), with liver metastasis (50%) and with peritoneal dissemination (64%). In cases of curative surgery, the incidence of PNI was significantly increased in MAC stage C2m+g or C3 (28%, 35%). There was no significant difference in the recurrence or survival rates between the patients with PNI and without PNI in MAC stage B2m+g. However, there was a significant increase in local recurrence in the patients with both PNI and lymph node metastasis (p less than 0.05). Also, the patients with PNI in MAC stage C2m+g had a significantly lower 8-year survival rate (29.1%, p less than 0.001). Multivariate analysis using Cox regression models demonstrated that PNI was an independent prognostic factor for survival. PMID- 1619889 TI - Distal enhancement of the occluded vessels on MRI in acute embolic cerebral infarction--intravascular enhancement sign. PMID- 1619890 TI - [Head injuries in children]. PMID- 1619891 TI - [Subarachnoidal hemorrhage--pathophysiology, symptoms and therapy]. PMID- 1619893 TI - [Decubitus ulcer--a theme without end?]. PMID- 1619892 TI - [Stress testing and work therapy in a phase II hospital]. PMID- 1619894 TI - [Cost effectiveness in hydrocolloid dressings compared to conventional dressings]. PMID- 1619895 TI - [Nursing standards shown for decubitus ulcers]. PMID- 1619896 TI - [Hygiene specialist--a profession is developing]. PMID- 1619897 TI - [Directions for appropriate relations with cancer patients and for the psychohygiene of the caregivers]. PMID- 1619898 TI - [In Africa as a nurse]. PMID- 1619899 TI - [Chaplaincy for the mentally ill]. PMID- 1619900 TI - Gender and ethnic differences in adolescents' attitudes toward condom use. AB - This secondary analysis from the National Adolescent Student Health Survey (NASHS) examined relationships between adolescents' personal and perceived peer attitudes toward condom use with gender and self-reported ethnic background. Descriptive results revealed general personal support and perceived peer support for condom use. Results from multivariate analysis of variance (MANOVAs) demonstrated significant interaction effects for the eighth grade sample [F = (4, 2383228) = 3530.01 p = .000], and the 10th grade sample [F = (4, 2636878) = 2594.41073, p = .000]. Contrasts revealed significant differences among all ethnic groups for both belief variables for the entire sample, eighth grade students, and 10th grade students. Though general support exists for condom use among U.S. eighth and 10th grade students, conviction varies among groups perhaps indicating a need for tailored messages about condom use, especially for Hispanic students. Implications for health education include the need for cultural sensitive and gender-sensitive STD education. PMID- 1619901 TI - Is school nursing really the "invisible practice"? PMID- 1619902 TI - The longevity of Growing Healthy: an analysis of the eight original sites implementing the School Health Curriculum Project. AB - The status of the Growing Healthy curriculum (School Health Curriculum Project [SHCP]) was examined in the eight sites selected in 1969 by the National Clearinghouse on Smoking and Health to receive funded training and implementation support. A contact person from each site completed and returned a questionnaire pertaining to the district's continued implementation (institutionalization) of the SHCP. Most districts had not continued to implement the program. Reasons for discontinuation included loss of the "program champion" and insufficient administrative leadership. Districts continuing to implement the program generally were smaller in size, and employed a part-time coordinator for the SHCP. Recommendations for institutionalizing future instruction programs include identifying replacement program coordinators and other administrators to ensure continuity and support for the program over time, and conducting process and impact evaluations on program effects. PMID- 1619903 TI - The status of school-based nutrition education at the state agency level. AB - The status of school-based nutrition education at the state agency level was examined. Telephone interviews with agencies in all 50 states revealed that nine states mandated nutrition be taught and another 21 included nutrition as a required topic in mandated subjects, frequently health. The other states had initiatives to promote school-based nutrition education but it was not required. Published requirements for teacher certification in elementary education, home economics, and health education seldom (two to three states) specified nutrition as a requirement. However, follow-up investigations revealed many states indirectly promote nutrition preparation for home economics and health education teachers through guidelines for approval of college programs in these areas. An inventory of nutrition education curricular materials revealed they were most frequently directed to grades K-6 and focused mainly on general foods and nutrition or that related to health. Given the links that emerged between health and nutrition, incorporating nutrition into health education may help promote school-based nutrition education. PMID- 1619904 TI - Comprehensive school-based services for pregnant and parenting adolescents in West Dallas, Texas. AB - A cohort of 339 Black (n = 210), Hispanic (n = 118), and other (n = 11) adolescent mothers in Dallas, Texas, were followed from the start of their pregnancy through the school year of the delivery to assess differences in numbers of prenatal care visits, postpartum care, repeat deliveries, and school continuation rates. Approximately one-half the teens received reproductive services at a comprehensive, school-based clinic and one-half at a categorical (Title XX) family planning and prenatal care clinic. Adolescents attending the school-based clinic were more likely to be in school at conception and averaged more prenatal visits than those served by the categorical provider. However, during the pregnancy and following the delivery, school dropout rates for the two sets of teens converged. School continuation rates were higher among a subset of adolescents attending the Dallas Independent School District school for pregnant teens than among other teens. Hispanic teens were two times more likely than their Black counterparts to drop out of school. No differences were found in repeat birth rates, by ethnicity, clinic site, or school attended. PMID- 1619906 TI - Papers presented at the Annual Meeting of the Association for Academic Surgery. Colorado Springs, Colorado, November 20-23, 1991. PMID- 1619905 TI - Multiple pathways in the rejection of skin grafts. AB - We have analyzed the ability of CD4+ and CD8+ T cells to cause rejection of skin grafts in an Ir gene high responder strain. (DA.RT1u x DA.RT1c)F1 B rats (thymectomized, lethally irradiated, reconstituted with fetal liver cells) were grafted with ear skin of the recombinant strain, DA.RT1rl. The only allogeneic difference was a single class I MHC antigen. The B rats, which do not reject these grafts due to the absence of T cells, were reconstituted at various time intervals after skin grafting with either unsorted lymph node cells (LNCs), CD4+, CD8+ or CD4+ and CD8+ T cells. Unsorted LNCs given any time after graft placement always caused rejection (MST = 15d). CD4+ cells alone never caused rejection (MST greater than 60d, n = 8). CD8+ cells alone caused rejection if given within 3 weeks of graft placement. Thereafter, CD8+ cells alone lost their ability to cause rejection (MST greater than 60d, n = 6). B rats with grafts in place more than 3 weeks, when CD8+ cells alone were ineffective, rejected their skin grafts when given both CD8+ and CD4+ cells. These data suggest that there may be two T cell pathways in skin graft rejection. The first requires only CD8+ cells and causes rejection of a recently placed graft. The second pathway requires both CD4+ and CD8+ cells to reject long-standing grafts in which donor antigen presenting cells have been putatively depleted and, therefore, may be dependent on host antigen-presenting cells. PMID- 1619907 TI - Evaluation of endothelium-derived nitric oxide mediated vasodilation utilizing ex vivo perfusion of an intact vessel. AB - The traditional evaluation of the endothelium-derived nitric oxide (EDNO) pathway involves isolated aortic rings with attached strain gauges. This model is nonphysiologic and does not permit studies lasting longer than several hours. Our objective was to overcome the limitations of these "traditional" methods utilizing a physiologic, whole vessel model as a reproducible assay of EDNO. Canine carotid arteries (n = 4) were removed (maintaining in vivo arterial geometry), mounted in a specially designed, continuous-flow circuit, and perfused at 100 ml/min, 80 mm Hg with Medium-199/10% canine serum. Physiologic pH, pCO2, pO2, and temperature were precisely regulated. A non-contacting, helium-neon laser micrometer was interfaced with the current system to provide continuous measurement of vessel external diameter and to quantitate changes in vessel wall geometry in response to epinephrine (EPI; 2 x 10(-5) to 2 x 10(-3) mg/ml) and acetylcholine (ACh; 0.1 to 100 microM) challenge. Further characterization of the perfusion system included the use of a competitive inhibitor to EDNO production, NG-monomethyl-L-arginine (L-NMMA), and the effect of this compound on ACh-induced vasodilation. The reversibility of this blockade was verified via the sequential addition of L-arginine (L-ARG; 0 to 3 mM). Data are expressed as the ratio of steady-state vessel cross-sectional area (CSA) following administration of vasoactive substance to the CSA prior to vasoactive challenge. Our results indicate that EPI and ACh produced significant dose-dependent vasoconstrictive and vasodilatory responses, respectively (P less than 0.001, ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619908 TI - Kupffer cell autoregulation of IL-1 production by PGE2 during hepatic regeneration. AB - The mammalian liver possesses the ability to regenerate to its original size after a 70% partial hepatectomy (PHx). The capacity of rat Kupffer cells (KC) isolated at specific intervals following PHx to produce interleukin-1 (IL-1) and prostaglandin E2 (PGE2) in response to endotoxin (LPS) was evaluated in standard RPMI-1640 (1200 microM L-arginine) and arginine-depleted RPMI-1640 (10 microM L arginine) media. Regenerating liver KC 48-120 hr following PHx responded to LPS with a significantly greater (p less than 0.05) production of IL-1 in standard RPMI-1640. When 10 microM L-arginine RPMI-1640 was used to simulate the high arginase activity low L-arginine levels of the hepatic microenvironment, regenerating liver KC production of IL-1 was further increased (p less than 0.05). During the same time period, regenerating liver KC also produced significantly (p less than 0.01) more PGE2 than sham KC in both high and low arginine media. When the cyclooxygenase inhibitor indomethacin (10 microM) was added to low arginine cultures, the PGE2 production was inhibited, and IL-1 production was upregulated (p less than 0.05). We conclude that during hepatic regeneration KC IL-1 production is elevated but controlled in an autoregulatory fashion by KC PGE2 production. PMID- 1619909 TI - Mast cell degranulation inhibits IL-2-induced microvascular protein leakage. AB - The therapeutic efficacy of interleukin-2 (IL-2) in the treatment of cancer has been limited by a "vascular leak syndrome" and related toxicities. To better understand the pathophysiology of the "vascular leak syndrome," we tested a hypothesis that mast cell degranulation mediated the acute increase in microvascular protein leakage seen immediately following IL-2 administration. After the cremaster muscle was prepared for intravital microscopy, anesthetized Sprague-Dawley rats were injected with fluorescein isothiocyanate-labeled albumin for fluorescent microscopy. Animals were treated by the intravenous injection of IL-2 (1 x 10(6) U/kg) (n = 6), the control IL-2-vehicle (n = 5), or IL-2 (1 x 10(6) U/kg) after mast cell degranulation with compound 48/80 (n = 6). Relative interstitial fluorescent intensity was quantitated by a computerized image analysis system as an index of microvascular protein leakage. IL-2 acutely induced protein leakage from the microcirculation. Mast cell degranulation with 48/80 prior to IL-2 treatment prevented protein leakage, but did not alter IL-2 induced leukocyte-endothelial adherence. These data suggest that mast cell mediated events may be responsible for the acute increase in microvascular permeability seen with IL-2 administration and that leukocyte-endothelial adherence alone is not solely responsible. PMID- 1619910 TI - Gut ischemia/reperfusion-induced liver dysfunction occurs despite sustained oxygen consumption. AB - We have previously shown that gut ischemia/reperfusion (I/R) causes liver dysfunction in vivo (increased [I125]albumin leak, decreased mitochondrial redox potential). Our purpose was to investigate liver dysfunction due to gut I/R in an ex vivo model where oxygen delivery (DO2) could be controlled. Rats underwent laparotomy (sham) or 45 min of superior mesenteric artery (SMA) occlusion (I/R) and 6 hr later the gut and liver were isolated in situ. Pressures were monitored while recirculating blood was perfused via the hepatic artery (2.5 ml/min) for 90 min and the SMA (7.5 ml/min) for the first 30 min, then the portal vein (7.5 ml/min) for 60 min. Both gut and liver DO2 and VO2 (Fick method) were maintained throughout the study period in the gut I/R as well as sham groups. Despite maintenance of liver VO2, however, gut I/R resulted in a marked and persistent reduction in bile flow. In conclusion, dysfunctional bile production after gut I/R is not due to impaired VO2, but rather gut-liver signaling yet to be defined. PMID- 1619911 TI - Upregulation of nutrient transport in fetal rabbit intestine by transamniotic substrate administration. AB - Delivery of nutrients to the developing fetal gastrointestinal tract has been advocated as a potential prenatal treatment for intrauterine growth retardation. To examine the effect of intrauterine nutrient administration on the uptake capacity of the intestine, 16 maternal rabbits underwent bilateral ovarian-end transamniotic catheter placement on gestational Day 24. Study fetuses received a galactose solution; the contralateral controls received mannitol, a physiologically inert carbohydrate. Infusions were continued until Day 30 when an everted sleeve technique was used to measure radiolabeled uptake of both galactose and glucose in the proximal, middle, and distal small intestine. Mucosal scrapes were obtained, weighed, and the percentage of weight was calculated. Results were analyzed by ANOVA and Student's t test with P less than 0.05 being considered significant. There were 2 maternal deaths with 11 fetal pairs surviving (79%). There was increased uptake of galactose in the study fetuses compared to controls reaching significance in the middle and distal segments. Similarly, glucose uptake was significantly increased in the proximal and distal segments. Mucosal weight was increased in all regions, reaching significance in the proximal segment. Total intestinal uptake of galactose and glucose was significantly increased in the study fetuses compared to controls. Intraamniotic galactose infusion caused not only upregulation of its own mucosal transport but also that of glucose, along the entire fetal small intestine, achieving statistical significance particularly in distal segments. Fetal implications for transamniotic feeding are under investigation. PMID- 1619912 TI - Newcastle disease virus selectively kills human tumor cells. AB - Newcastle disease virus (NDV), strain 73-T, has previously been shown to be cytolytic to mouse tumor cells. In this study, we have evaluated the ability of NDV to replicate in and kill human tumor cells in culture and in athymic mice. Plaque assays were used to determine the cytolytic activity of NDV on six human tumor cell lines, fibrosarcoma (HT1080), osteosarcoma (KHOS), cervical carcinoma (KB8-5-11), bladder carcinoma (HCV29T), neuroblastoma (IMR32), and Wilm's tumor (G104), and on nine different normal human fibroblast lines. NDV formed plaques on all tumor cells tested as well as on chick embryo cells (CEC), the native host for NDV. Plaques did not form on any of the normal fibroblast lines. To detect NDV replication, virus yield assays were performed which measured virus particles in infected cell culture supernatants. Virus yield increased 10,000-fold within 24 hr in tumor and CEC supernatants. Titers remained near zero in normal fibroblast supernatants. In vivo tumoricidal activity was evaluated in athymic nude Balb-c mice by subcutaneous injection of 9 x 10(6) tumor cells followed by intralesional injection of either live or heat-killed NDV (1.0 x 10(6) plaque forming units [PFU]), or medium. After live NDV treatment, tumor regression occurred in 10 out of 11 mice bearing KB8-5-11 tumors, 8 out of 8 with HT-1080 tumors, and 6 out of 7 with IMR-32 tumors. After treatment with heat-killed NDV no regression occurred (P less than 0.01, Fisher's exact test). Nontumor-bearing mice injected with 1.0 x 10(8) PFU of NDV remained healthy. These results indicate that NDV efficiently and selectively replicates in and kills tumor cells, but not normal cells, and that intralesional NDV causes complete tumor regression in athymic mice with a high therapeutic index. PMID- 1619913 TI - Site-specific variations in basal and meal-stimulated intestinal absorption. AB - The ingestion of a meal increases water and electrolyte absorption in the proximal jejunum. The purpose of these experiments was to elucidate any site specific variations in intestinal absorption, comparing jejunum to ileum, in both the basal and the meal-stimulated states. Twenty-five-centimeter proximal jejunal and distal ileal Thirty-Vella fistulae were constructed in four dogs. Simultaneous jejunal and ileal absorption studies were performed using [14C]PEG to calculate net absorption of water and electrolytes. Two groups were studied: in Group 1 no meal was ingested, while in Group 2, the animals ingested a mixed meal. Each study consisted of a 1-hr basal period and a 3-hr experimental period. In the basal state ileal absorption significantly exceeded jejunal absorption (P less than 0.0001). The ingestion of mixed meal significantly increased water and electrolyte absorption in both the jejunum and the ileum, (P less than 0.001), with the magnitude of meal-stimulated ileal absorption significantly exceeding the magnitude of meal-stimulated jejunal absorption (P less than 0.001). These studies demonstrate distinct site specific variations in intestinal water and electrolyte absorption in both the basal and the meal-stimulated states. PMID- 1619914 TI - Pulmonary arterial impedance after single lung transplantation. AB - Single lung transplantation (SLT) is emerging as definitive therapy for end-stage pulmonary disease of varying etiology, yet a complete description of the hemodynamic properties of the transplanted lung has not been reported. In this study, Fourier analysis was used to calculate the pulmonary arterial (PA) impedance spectrum before and immediately after SLT to define precisely the pulmonary pressure-flow relationship. Median sternotomies were performed in 18 dogs (donors): an ultrasonic flow probe was placed around the PA and micromanometers were placed in the PA and left atrium (LA). Control PA pressure and flow (PAQ) and LA pressure were measured during transient occlusion of the right PA. The lungs were harvested using cold modified Euro-Collins solution for preservation. After thoracotomy and pneumonectomy, left SLT was performed in 18 recipient dogs with a mean ischemic time of 179 +/- 6 min. After reperfusion for 1 hr, PA pressure and flow data were again collected. Characteristic impedance (Z0), a measure of resistance to pulsatile flow, was compared to input resistance (Rin), a measure of resistance to mean flow, and pulmonary vascular resistance (PVR), the conventional index. Rin is defined as the zeroth harmonic of the impedance spectrum and Z0 as the mean of impedance moduli from 2-12 Hz. All recipients survived transplantation. Both PVR and Rin increased significantly after transplantation (11 +/- 1 vs 19 +/- 3 Wood U, P less than 0.05, and 1352 +/ 121 vs 1964 +/- 244 dyne.sec.cm-5, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619916 TI - Molecular mechanism of contractile dysfunction in cardiac allograft rejection. AB - Alterations in the beta-adrenergic receptor adenylyl cyclase pathway are well known in heart failure. To determine if an alteration in this pathway occurs during the reversible phase of cardiac allograft rejection, we used a rat heterotopic heart transplant model. Lewis rats received either isografts or Lewis Brown Norway allografts. Cardiac grafts and native hearts were explanted 4, 5, or 6 days later. Receptor-mediated modulation of adenylyl cyclase activity was investigated using isoproterenol, forskolin, and the muscarinic and adenosine receptor agonists carbachol and R-N6-(C2-phenyl-isopropyl)-adenosine (R-PIA), respectively. Allografts demonstrated evidence of histological rejection and a significantly impaired response to forskolin and isoproterenol on all days: [table: see text] (% increase in cAMP in response to forskolin or isoproterenol +/- standard error. All results P less than 0.03 except Day 4 forskolin and Day 5 isoproterenol.) No significant difference was noted between isografts and allografts stimulated with carbachol and R-PIA. These data suggest that a primary alteration in adenylyl cyclase activity may be a component of the molecular basis of reversible contractile dysfunction in cardiac allograft rejection. PMID- 1619915 TI - Correlation of hepatic injury, synthetic function, and mitochondria energy level in orthotopic liver transplantation. AB - The arterial ketone blood ratio (AKBR) of acetoacetate to b-hydroxybutyrate was previously shown to reflect hepatic mitochondria oxidation/reduction (redox) state and energy level. In this study we correlated AKBR to the degree of liver injury immediately following orthotopic liver transplantation (OLT). Serial measurements of AKBR in 209 patients undergoing OLT, during the anhepatic phase, and up to 60 hr following reperfusion demonstrated direct correlation between mitochondria Redox state (AKBR), hepatocyte injury (SGOT), and hepatic synthetic function (prothrombin time). AKBR levels less than 0.7 were seen in primary nonfunction grafts and were associated with raising SGOT (greater than 1000) and prolonged PT (greater than 18). Acute occlusion of arterial blood supply to the graft was seen in conjunction with low AKBR (less than 0.7). However, hepatic synthetic function and serum enzyme were stabilized or returned to normal within 24-48 hr postreperfusion. IN CONCLUSION: (1) AKBR measurements are useful in predicting graft survival, (2) reduction in liver mitochondria Redox state is seen in primary hepatocyte dysfunction and correlates well to synthetic function, and (3) acute occlusion of the arterial supply to the liver graft is associated with decreased redox state. However, with intact portal blood flow, it is still possible to preserve adequate hepatic synthetic function. PMID- 1619917 TI - High energy phosphate depletion in leaflet matrix cells during processing of cryopreserved cardiac valves. AB - Preimplantation preparation of cardiac valves includes three major steps: (1) harvesting with accompanying ischemia (warm time from cessation of donor heart beat), (2) antibiotic disinfection, and (3) controlled-rate cryopreservation. To define the interdependent injury effects of these manipulations on leaflet matrix cells and specifically the potential for prolonged harvest-related ischemia to predispose greater injury by the subsequent steps, 96 semilunar valves were harvested from pigs in a manner analogous to human heart valve retrievals and randomly allocated to study groups as follows: 48 control valves were exposed to increasing harvested-related ischemic times, (2, 6, 12, 24 hr) and immersed in liquid nitrogen to arrest metabolic activity (i.e., prior to cryopreservation) and conclude the ischemia; another 48 were similarly harvested, subjected to identical ischemic times, then disinfected in 4 degrees C RPMI medium with standard antibiotics for 24 hr and dimethylsulfoxide cryopreserved at -1 degrees C/min to -170 degrees C (i.e., formal cryopreservation protocol). At thawing, each valve was extracted in 12% trichloroacetic acid and assayed by high performance liquid chromatography for components of the adenine nucleotide pool including ATP, lower energy nucleotides (total adenine nucleotides, [TAN] = [ATP] + [ADP] + [AMP]), adenosine, and the diffusible purines. Results are reported as nanomoles metabolite/milligram of leaflet cell protein (Lowry) and reflect a maintenance of total high energy phosphates in the control groups (5.41 +/- 0.29 nmole TAN at 2 hr; 8.34 +/- 0.67 nmole TAN at 24 hr), which fell significantly in all cryopreserved groups (1.27 +/- 0.33 nmole TAN at 2 hr; 0.34 +/- 0.22 nmole TAN at 24 hr).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619918 TI - Endotoxin suppresses matrix protein-induced upregulation of PMN candicidal activity: an effect reversed by low-dose TNF-alpha. AB - We investigated the relationship of polymorphonuclear leukocyte (PMN) candicidal activity, matrix proteins, and lipopolysaccharide (LPS) to determine how LPS modulates the normal enhancing effect of matrix proteins on PMN candicidal activity. LPS reduced PMN candicidal activity when PMN were adhered in the presence of either fibronectin or laminin. In the presence of fibronectin or laminin, LPS reduced CD11b/CD18 expression (the fibronectin receptor) as assessed using sheep erythrocytes coated with C3bi. Experiments with 125I-fibronectin and 125I-RGDS (Arg-Gly-Asp-Ser) demonstrated that LPS reduced both the binding of fibronectin and the bioavailability of the binding epitope on the PMN surface. Stimulating the PMN oxidative burst with PMA but not FMLP also reduced fibronectin and RGDS binding. Incubation of LPS-treated PMN with staurosporine blocked the decrease in fibronectin and RGDS binding. Exposure of PMN to LPS plus low-dose TNF-alpha restored both fibronectin and RGDS binding with a concomitant increase in CD11b/CD18 surface expression. Low-dose TNF-alpha restored PMN candicidal activity in the presence of LPS and was most effective if PMN were preadhered to fibronectin. These results demonstrate that: (1) matrix proteins enhance normal PMN candicidal activity, (2) LPS reduces PMN candicidal activity in the presence of matrix proteins, (3) stimulation of the PMN oxidative burst in particular via protein kinase c activation reduces the bioavailability of the fibronectin receptor, and (4) low-dose TNF-alpha may restore PMN candicidal activity in part by upregulating the surface receptor for fibronectin binding. PMID- 1619919 TI - Intestinal blood flow is restored with glutamine or glucose suffusion after hemorrhage. AB - Intestinal blood flow has been shown to be impaired after resuscitated hemorrhagic shock. Enteral feeding has been proposed as an adjunct for preserving mucosal integrity and decreasing translocation-related morbidities during stress. The purpose of this study was to determine if an ileal mucosal suffusion with an isotonic glucose or glutamine solution begun after resuscitation would prevent development of this blood flow impairment. The distal ileum of anesthetized Sprague-Dawley rats was prepared for in vivo videomicroscopy. Animals were bled to 50% of baseline blood pressure for 60 min and then resuscitated with their shed blood and an equal volume of lactated Ringer's. After resuscitation was complete, the mucosa was suffused with isotonic glucose, glutamine, or saline (control). Resuscitation restored cardiac output and mean arterial pressure to baseline in all groups; however, first-order arteriolar blood flow remained 50% below baseline in the saline group. Glucose-treated animals demonstrated a 34% increase over baseline in first-order arteriolar blood flow 120 min after resuscitation due to submucosal and previllus arteriolar dilation. This effect became evident 30 min after initiating the suffusion, suggesting an effect mediated via locally generated vasodilators. Glutamine suffusion attenuated the flow impairment by dilation of previllus arterioles but to a lesser degree than that observed in glucose-treated animals. These data demonstrate that mucosal suffusion with an isotonic glucose solution overrides the residual effects of hemorrhagic shock on the intestinal microcirculation and suggest a mechanism for preserving mucosal integrity with the addition of glutamine to standard enteral formulations. PMID- 1619920 TI - In vivo [31P]NMR assessment of early hepatocellular dysfunction during endotoxemia. AB - Hepatocellular dysfunction, as a result of sepsis or endotoxemia, plays a critical role in the pathogenesis of multiple systems organ failure. Conventional methods to assay hepatic ATP require large tissue samples, making repeat measurements in the same animal impossible, and are unable to detect the minimal changes in metabolism consistent with early or reversible cellular injury. 31P NMR is a modality available for the in vivo measurement of high energy phosphates. Inorganic phosphate (Pi) and phosphomonoester (PME) ratios (markers of cellular metabolism and viability) as well as fractionated ATP may be repeatedly quantitated. To assess the early effects of endotoxemia on hepatic function, phosphorus spectra of the liver were obtained using a 1.7-cm surface coil in six rats after the ip administration of 4 mg/kg Escherichia coli lipopolysaccharide. Conventional assay was performed on 24 matched controls. Pi, PME, alpha-, beta-, and gamma-ATP peaks (expressed as percentage total signal area) were collected over 20 min, integrated, and analyzed. Pi/beta-ATP decreased over time until 6 hr reflecting ongoing uptake of inorganic phosphate and continued cellular metabolism. PME/beta-ATP ratios, which indicate cellular viability, became significantly elevated at 6 hr. Using 31P NMR, beta-ATP best reflected the early subtle energy changes present prior to cell death and subsequent organ failure with significant decreases at 2, 4, and 6 hr. Conventional assay for ATP confirmed similar trends. We conclude that 31P NMR is a valuable tool for the study of reversible hepatic energy changes during early endotoxemia. PMID- 1619921 TI - Interleukin 1 beta improves survival following cecal ligation and puncture. AB - Despite antibiotic therapy intra-abdominal sepsis following major surgery is a significant cause of mortality. We sought to determine if interleukin-1 beta (IL 1) could improve survival in a murine model of intra-abdominal infection. Groups of 10 BDF1 mice received a single subcutaneous (sc) injection of recombinant human IL-1 beta 24 hr prior to cecal ligation and puncture (CLP) and were assessed twice daily for survival. Mice that received a single injection of IL-1 beta 24 hr prior to CLP had a dose-dependent improval in survival compared to controls. The beneficial effect of IL-1 treatment may have been related to its ability to stimulate myelopiesis. The addition of indomethacin, in an effort to limit possible toxicity of IL-1, did not further improve survival. Appropriate timing of specific immunomodulators may provide an additional strategy for the treatment of infections. PMID- 1619922 TI - Lymphocyte migration to tumors after hyperthermia and immunotherapy. AB - We have previously shown that the combination of immunotherapy with interleukin 2 (IL-2) and local hyperthermia (LHT) abrogates the growth of murine subcutaneous tumors significantly more than either modality alone. This study was undertaken to investigate whether the beneficial effect of combined modality therapy could be attributed to increased trafficking of effector cells to the tumor. After inducing MCA-105 sarcomas in the hindlimbs of C57BL/6 mice, animals were given no therapy, LHT, IL-2, or IL-2 + LHT followed by an iv injection of 51Cr-labeled syngeneic splenocytes or LAK cells. Select organs and the tumor-bearing extremity were counted in a gamma counter. IL-2 or LHT alone did not affect lymphocyte migration, while IL-2 + LHT significantly decreased trafficking (P less than 0.001) to the tumor. LAK cells showed increased migration to the tumor site compared to splenocytes in all treatment groups (P less than 0.02). IL-2 caused increased migration of LAK cells but not splenocytes to the lung; this was not affected by LHT. LAK cell trafficking to the spleen was decreased by IL-2 and IL 2 + LHT, while splenocyte migration was decreased in the LHT and combined treatment groups. LHT and IL-2 had no effect on trafficking of either effector cell type to liver or kidney. These results show that the beneficial effect of combined modality therapy may not be due to increased trafficking of lymphocytes to the tumor area. In addition, LAK cells traffic more to subcutaneous tumors than splenocytes, and this cannot be explained by the differential trafficking to other organs. The results of this study will be important in the planning of future experiments with combined adoptive immunotherapy and hyperthermia. PMID- 1619923 TI - The reduction of health care costs associated with alcoholism treatment: a 14 year longitudinal study. AB - This study utilized two separate research designs to examine whether the initiation of alcoholism treatment is associated with a change in overall medical care cost in a population of alcoholics enrolled under a health plan sponsored by a large midwestern manufacturing corporation. In the longest longitudinal study of alcoholism treatment costs to date, a review of claims filed from 1974 to 1987 identified 3,729 alcoholics (3,068 of whom received treatment and 661 of whom did not). In one design, a time-series analysis found that following treatment initiation the total health care costs of treated alcoholics--including the cost of alcoholism treatment--declined by 23% to 55% from their highest pretreatment levels. Costs for identified but untreated alcoholics rose following identification. In a second design, analysis of variance was used to control for group differences including pretreatment health status and age. This analysis indicated that the posttreatment costs of treated alcoholics were 24% lower than comparable costs for untreated alcoholics. The study provides considerable evidence that alcoholism treatment can reduce overall medical costs in a heterogeneous alcoholic population (white collar/blue collar; fee-for service/HMO). PMID- 1619924 TI - Drinking among homeless and marginally housed adults in New York State. AB - The drinking patterns of 412 homeless and marginally housed adults in New York State are described, and compared with 5,952 domiciled adults. The homeless and marginally housed persons interviewed were randomly selected from a representative group of public shelters and low-price hotels in New York City and upstate New York. They showed transience in their sleeping arrangements, and in recent months many had slept with friends or in public places. They are disproportionately male (71%), aged 18-34 (61%) and black or Hispanic (74%). Many of the homeless and marginally housed are abstainers (40%, as opposed to 26% in the state as a whole), but a startling 13% drink more than 20 drinks a day, as opposed to less than 1% in the state as a whole. They also reported high rates of dependence signs such as blackouts or loss of control. Among the homeless and marginally housed, heavy drinking is higher among men than women, and higher among blacks than whites or Hispanics. For homeless and marginally housed men, those with the poorest sleeping arrangements (e.g., slept in public places) have higher rates of heavy drinking. A causal model supports the hypothesis that, for a minority of the homeless, drinking is a contributory cause of their homelessness. PMID- 1619925 TI - Recruiting a community sample of adolescent children of alcoholics: a comparison of three subject sources. AB - Although there has been substantial research interest in adolescent children of alcoholics, the generalizability and consistency of previous findings have been limited by the specialized nature of the research samples (e.g., treatment samples, school-based samples). However, attempting to address this problem by recruiting subjects from community sources raises a variety of sampling issues, including the comparability and accessibility of subjects from different sources. This article compares the recruitment rates and characteristics of families enrolled from three sources--DUI records, HMO records and telephone surveys. Implications for research on children of alcoholics are discussed. PMID- 1619926 TI - Familial alcoholism and premorbid cognitive deficit: a failure to replicate subtype differences. AB - Recent evidence suggests that offspring of alcoholics are heterogeneous in many areas of functioning. This study focuses on extending our understanding of the vulnerability and resilience of young adults with a positive family history of alcoholism (FH+) within the domain of neurocognitive functioning. Specifically, we test the hypothesis that cognitive vulnerability is linked to genetic pedigree by systematically examining a broad range of cognitive abilities in several distinct family history subtypes represented by alcoholism on the part of a first degree relative only, a second-degree relative only, or both a first- and second degree relative. Compared to an age-matched control group with no family history of alcoholism (FH-), FH+ subjects, on the average, reported somewhat less formal education than did FH- subjects. However, no substantive differences in cognitive functioning were obtained among any family history subtypes. Nor were any predicted yet nonsignificant trends in the ordering of mean cognitive performance levels observed across groups. These results strongly suggest that cognitive deficits do not generally obtain in community samples of premorbid FH+ subjects, and, further, that specific genetic pedigrees, as defined in this study, do not contribute to variability in neuropsychological functioning. A typological approach wherein subtypes of FH+ individuals are defined multidimensionally may be necessary to capture sources of neurocognitive vulnerability in premorbid offspring. PMID- 1619927 TI - Laboratory evaluation of two passive alcohol sensors. AB - Passive alcohol sensors are screening devices designed to sample nonintrusively the exhaled breath of a person to determine whether or not it contains alcohol and if so approximately how much. Two production passive alcohol sensors (NPAS passive alcohol sensor and the Life-Loc PBA 2000) were evaluated in a laboratory environment to establish appropriate threshold measurements that indicate probable alcohol impairment. The laboratory evaluation was conducted using both instrument types with 12 drinking subjects. Both sensors were able to identify alcohol in exhaled breath with sufficient accuracy to identify persons with high blood alcohol concentrations (BACs). The accuracy of both sensors was related to the distance from the subject's mouth: the further away they were from a subject's mouth the greater the chance that high BACs would not be detected. Under ideal conditions, it was estimated that the Life-Loc sensor could be expected to correctly detect 80% of drivers at 0.10% BAC (99% at 0.15% BAC) as being impaired while incorrectly identifying only about one in eight drivers with BACs of 0.02% (false positives). In comparison, the NPAS sensor could be expected to correctly detect about 75% of drivers at 0.10% BAC (97% at 0.15% BAC) while incorrectly identifying one in five drivers at 0.02% BAC. PMID- 1619928 TI - Convicted impaired drivers and high-risk drivers: how similar are they? AB - The present study was a partial replication of one by D.M. Donovan (1980). Donovan's results indicated that convicted impaired drivers (DWIs) and high-risk drivers were overlapping populations with shared deviant characteristics. The present study, like Donovan's, compared three types of drivers: DWI, high-risk (either high-accident or high-violation) and general population control. Unlike Donovan, the present study attempted to match the age and sex distributions of the groups. Data were obtained from personal interviews and driver records. The DWI group was the most deviant on behavioral and personality measures and had more accidents and traffic convictions than did controls. High-risk drivers were more deviant than controls on several measures but the two groups were quite similar in other respects. The results suggest that some of the deviance attributed to high-risk drivers by Donovan may have been exaggerated by confounding with age. Secondly, the heterogeneity within the DWI and high-risk driving populations appears to outweigh their differences. PMID- 1619929 TI - Variability in behavioral impairment involved in the rising and falling BAC curve. AB - The purpose of this pilot study was to measure variability in behavior impairment at specific levels of the rising and falling blood alcohol concentration (BAC) curve. Behavior impairment was measured for anticipation and reaction time in addition to a variety of visual skills. Also of interest was the variability in impairment involved at specific BAC levels under single-dose and double-dose conditions. The experimental design was a variation on a 2 x 2 factorial with repeated measures on the dose of alcohol. All subjects took part in two experimental sessions, single-dose and double-dose. Sixteen (8 male and 8 female) paid subjects ages 21-40 participated in the study. Testing procedures included repeated measures on reaction time, anticipation time, perceptual vision acuity and depth perception. Breath-alcohol measures were sampled continuously at 5 minute intervals and used to plot absorption time, peak BAC and elimination time. Results showed that the average peak BAC for the double-dose was significantly higher than that of the single-dose condition. However, there were no significant differences between the single-dose and double-dose condition in either absorption time or elimination time. The performance pattern for reaction time, anticipation time and depth perception showed more impairment in the rising BAC limb than in the falling BAC limb. It is noteworthy that specific individuals exhibited different levels of impairment at a given BAC level, depending on whether the session was single- or double-dose, suggesting that one's current BAC level is less a measure of impairment than is the total quantity of alcohol consumed. A follow-up procedure to examine practice effects was conducted on eight volunteer students. Identical testing procedures, using no alcohol, produced no significant practice effects after a 3-hour period. PMID- 1619930 TI - Combat-related posttraumatic stress disorder and severity of substance abuse in Vietnam veterans. AB - This study examined the effects of Vietnam war-zone duty and combat-related posttraumatic stress disorder (PTSD) on severity of drug- and alcohol-abuse disorders among veterans seeking treatment for substance dependence. Combat exposed Vietnam-theater veterans (N = 108) were compared with Vietnam-era veterans without war-zone duty (N = 151) on psychometric measures of drug and alcohol abuse. There were no differences between theater and era veterans on these measures. However, Vietnam-theater veterans with PTSD experienced more severe drug- and alcohol-abuse problems than did theater veterans without PTSD and were at greater risk for having both forms of substance abuse. Further analyses showed that PTSD was significantly related to some dimensions of drug- and alcohol-abuse problems but not to other dimensions. These findings indicate that PTSD, rather than combat stress per se, is linked to severity of substance abuse. Finally, reexperiencing and avoidance/numbing components of PTSD were more strongly associated with drug abuse than alcohol abuse, but physiological arousal symptoms of PTSD were more highly correlated with alcohol abuse. PMID- 1619931 TI - The effect of acculturation on drinking attitudes among Japanese in Japan and Japanese Americans in Hawaii and California. AB - Data from a joint Japan-U.S. collaborative study were examined to determine the relationship of acculturation to drinking attitudes among Japanese in Japan and Japanese Americans in Hawaii and California. Drinking attitudes (i.e., self reported acceptable or appropriate levels of drinking) among ethnic groups differed significantly for the nine situations studied: (1) at a bar with friends, (2) at a party at someone else's house, (3) as a parent, spending time with small children, (4) during working hours, (5) visiting in-laws, (6) with friends at home, (7) with friends after work, (8) with people at sports events and (9) before driving a car. Factor analysis was used to determine the differences in drinking attitudes among these ethnic groups. Japanese and Japanese Americans differentiated drinking situations into different categories. The major difference between the two groups was that the Japanese associated spending time with small children with a situation appropriate for drinking, such as being with friends at home, whereas Japanese Americans associated spending time with small children with a situation inappropriate for drinking, such as before driving. PMID- 1619932 TI - Cardiac responsivity in individuals at high risk for alcoholism. AB - Heart rate was recorded from male siblings over the age of 30 who were members or either alcoholic or control families. Brothers from alcoholic families included both those with a diagnosis of alcoholism (n = 66) and those without such a diagnosis (n = 18). Control brothers (n = 33) were chosen for absences of any Axis I psychopathology including alcoholism in all first- and second-degree relatives. Subjects were engaged in two auditory tasks. All subjects were presented with high- and low-pitched tones with varying probabilities. In the first task (counting), subjects were told to count only the number of high tones. In the second task (choice reaction), subjects were asked to perform a simple motor response to each high or low tone. Prestimulus levels, anticipatory deceleration and acceleration were compared between the three groups. All members of the affected families, whether alcoholic themselves or not, were found to have a significantly higher baseline heart rate than members of control families. In addition, differences in the anticipatory deceleration were greater in control brothers than in brothers from the affected families for the counting task. PMID- 1619933 TI - Detection of the relationship between moderate alcoholic beverage consumption and serum levels of estradiol in normal postmenopausal women: effects of alcohol consumption quantitation methods and sample size adequacy. AB - The purpose of this study was to evaluate the detectability of an effect of moderate alcoholic beverage consumption on the biologic correlate of postmenopausal estradiol levels. Total weekly consumption and beverage-specific intake were assessed using both self-reported usual consumption information and prospective food record data. In terms of total weekly drinks, discrepancies were observed in 35 of the 101 women who reported alcohol use; no consistent pattern of overreporting/underreporting was seen. Although the two alcohol estimates were highly correlated, the relationship between estradiol levels and total weekly alcohol intake was found to be detectable when alcohol consumption based on the food record data was analyzed, but not when the self-report data were examined in a two-tailed hypothesis-testing situation. Evaluating the association between postmenopausal estradiol levels and the two estimates of alcohol intake in random samples of varying sample sizes generated from the mother population of 128 normal postmenopausal women confirmed the finding that the prospectively obtained alcohol data better predict the relationship. Based on the results of this study, it must be concluded that self-reported usual alcohol consumption data must be used with caution when examining an association between alcohol intake and a biologic effect. PMID- 1619935 TI - Adjuvant immunotherapy in melanoma: a new approach. AB - Patients with metastatic cutaneous melanoma to two or more regional lymph nodes have an extremely poor prognosis despite radical lymphadenectomy. In an attempt to improve the survival and to determine the safety of a new method of tumor specific adjuvant immunotherapy in such a high risk group of patients, nine patients were studied. Three to four weeks after regional lymphadenectomy, each of them received a single intradermal injection of Bacillus Calmette-Guerin. Three weeks later, they were immunized by allogenic melanoma cells obtained from live donors with distant metastases. Each patient received three vaccinations, each from a different donor (except in one), to avoid development of HLA response, but maintaining exposure to melanoma antigens. No cultured melanoma cells were used. Each vaccine consisted of mitomycin-C treated tumor cells mixed with purified protein derivative (PPD) of tuberculin given intradermally once per month for 3 months. The patients were then observed with no further treatment. Utilizing the leukocyte migration inhibition test, there was some in vitro evidence of tumor specific cell mediated response which seemed to disappear 1-2 months postimmunization. At 5 years, five of the nine patients (55%) were alive free of disease. No autoimmune diseases were detected in any of the immunized patients. A major hindering factor for such an approach was the limited availability of the allogenic melanoma cells. PMID- 1619934 TI - Primary malignant tumors of the small intestine: analysis of 40 Japanese patients. AB - Forty Japanese patients with primary malignant tumors of the small intestine were reviewed. Adenocarcinoma was the most common tumor type comprising 19 patients (47%), followed by malignant lymphoma, 11 (30%), leiomyosarcoma, 8 (20%) and carcinoid tumor, 1 (3%). Adenocarcinomas and leiomyosarcomas were primarily located in the duodenum or jejunum, whereas lymphomas were more common in the jejunum or ileum. Abdominal pain (65%) and nausea or vomiting (35%) were the most common symptoms with these tumors. Barium contrast studies were able to detect 83% of these tumors. Our results also suggest that computed tomography and ultrasonography are not reliable for diagnosing jejunal tumors while superior mesenteric angiography is effective for diagnosing ileal tumors. The duodenal and ileal tumors tended to metastasize to lymph nodes while jejunal ones tended to penetrate the serosa or to disseminate into the peritoneal cavity. The percentage of tumors potentially cured by surgery and the 5 year survival rates of the leiomyosarcomas (75% and 57%, respectively) were higher than those of adenocarcinomas (42% and 10%, respectively) and lymphomas (42% and 32%, respectively). PMID- 1619936 TI - Functional results following esophagogastrectomy for carcinoma of the esophagus. AB - Fifty patients underwent esophagogastrectomy for histologically proven carcinoma of the esophagus from January to December 1989. The Ivor Lewis procedure was performed in 29 patients and 21 resections were performed by a left thoracoabdominal approach. There was one anastomotic leak which could not be salvaged and was responsible for the sole mortality within 30 days of surgery. The hospital stay averaged 12 days, ranging from 8-26 days. Swallowing was resumed by the 6th postoperative day for liquids and 8th day for soft solids. Following surgery, 5 patients developed dysphagia, 4 of whom responded to dilatation. The anastomosis was hand sutured in all cases except one. The suture material used had no relation to the incidence of leak or stricture formation. Eight patients complained of reflux that settled with medical management. Most patients were eating without dysphagia at the last follow-up or death. Esophagogastrectomy can be performed with a low morbidity and mortality and provides adequate palliation of the patient's most distressing symptom, dysphagia. PMID- 1619937 TI - Comparison of flow cytometric DNA content in primary gastric carcinoma and metastases. AB - Nuclear DNA contents were comparatively determined by flow cytometry in primary and metastatic lesions from 112 cases with stomach cancer. Aneuploidy frequency and mean DNA index were higher in lymph node metastatic lesions than in primary lesions, both resected synchronously. In these lymph node metastatic lesions, DNA ploidy patterns did not change in 79% (89/112 cases), and did change in 21% (23/112 cases). Concordance of the DNA index between primary lesions and synchronous liver metastatic lesions was seen in 63% (5/8 cases), but the concordance rate was only 25% (4/16 cases) for primary lesions and metachronous liver metastatic lesions and 0% (0/8) for primary lesions and lung metastases. DNA ploidy changes in metastatic lesions were marked in distal metastatic lesions, or more marked in metachronous metastases than in synchronous ones. The results of the present study suggested the possibility of detecting changes in biological characteristics of metastatic lesions by flow cytometric DNA analysis. PMID- 1619938 TI - Substituting ornithine for arginine in total parenteral nutrition eliminates enhanced tumor growth. AB - Total parenteral nutrition (TPN) may enhance the growth of some tumors: this enhanced growth is associated with an increase in the erythrocyte polyamine levels. The effect of arginine in TPN on tumor growth was compared with ornithine using rats with a transplantable Ward colon tumor. The relationship of circulating arginine, ornithine, glutamine, and polyamines with tumor growth was investigated. For rats fed chow ad libitum, increasing tumor weights were associated with a linear decrease in the plasma arginine levels which was consistently lower than that of age-matched non-tumor bearing (NTB) rats; ornithine and lysine levels were not affected. Subsequent experiments suggest that plasma glutamine levels were also lower in tumor bearing rats. Pair-fed NTB rats had reduced arginine but not glutamine levels in plasma. TPN regimens with arginine or with ornithine substituted for arginine at two levels (equimolar [Orn Em] or isonitrogenous [Orn-IN]) were given to colon tumor bearing rats for 8 days. The final tumor weight of rats which received the arginine-containing regimen (19.8 +/- 5.7 g, n = 4) (P less than 0.05) was significantly greater than the tumor weight of rats fed chow ad libitum (12.1 +/- 3.3 g, n = 6). The final tumor weights of Orn-EM (11.2 +/- 2.6 g, n = 4) or Orn-IN (11.6 +/- 0.8 g, n = 6) were similar to the chow-fed controls. The plasma arginine levels were elevated, compared with the control, when arginine was present in the regimen. The plasma arginine levels of rats which received Orn-EM or Orn-IN were lower than the controls. The plasma ornithine levels were not affected by arginine in the regimen but were elevated with increasing levels of ornithine in TPN. Plasma glutamine levels were decreased when arginine was present in the regimen but were elevated when ornithine was substituted for arginine. Erythrocyte putrescine was increased when either arginine or ornithine was included in the TPN regimens. These results demonstrate that while arginine in a parenteral regimen stimulates tumor growth, substituting ornithine for arginine in TPN does not enhance the growth of a transplantable colon tumor. PMID- 1619939 TI - Prognostic significance of DNA measurement determined by image analysis in human breast carcinoma. AB - The nuclear DNA of human breast carcinoma cells was studied by image analysis using archival paraffin-blocked tissues from two groups of patients with breast cancers. One group had survived greater than 10 years (N = 20) and the other less than 3 years (N = 26) after the initial diagnosis. Cellular preparations were made from pepsin-digested deparaffinated sections. The nuclear DNA was stained with Feulgen stain and measured by a computerized image analysis system. The data show that in addition to nodal status the pattern of DNA histograms obtained from image analysis can provide powerful prognostic information in breast carcinoma. The prognostic value of DNA histogram patterns may be independent of nodal status. PMID- 1619940 TI - Biodistribution of monoclonal antibody A7 and its F(ab')2 fragment in athymic nude mice bearing human pancreatic carcinoma. AB - Xenografts of a human pancreatic carcinoma cell line, HPC-YS, which reacted with the monoclonal antibody (MAb) A7, were used to investigate the in vivo localization of radioiodinated MAb A7 after intraperitoneal injection. MAb A7 localized to the tumor 4 days and 8 days after injection with a tissue/blood ratio of 1.45 +/- 0.18 and 2.04 +/- 0.20, respectively. The accumulation of MAb A7 in the tumor was 5%/g and 3.3%/g of the injected dose on day 4 and on day 8, respectively. In contrast, the F(ab')2 fragment of MAb A7 localized to the tumor 4 days after intravenous injection with a tissue/blood ratio of 14.2. The accumulation of the F(ab')2 fragment in the tumor was 1.2%/g of the injected dose. These results suggested that MAb A7 might be a suitable carrier of anticancer drugs for immunotargeting chemotherapy and that the F(ab')2 fragment might be potentially useful for the immunodetection of human pancreatic carcinomas. PMID- 1619941 TI - Cancer of the esophagus in young adults. AB - Clinicopathological features and survival data of squamous cell carcinoma of the esophagus were analyzed from the viewpoint of age differences in 453 patients treated at the Tata Memorial Hospital, Bombay, India. Two groups were studied: group A, aged 35 years or less; and group B, aged above 35 years. There was no significant difference among the two groups with regard to sex distribution, site and length of the tumor, operability, morphology, histological grade, vascular and lymphatic invasion, and lymph node metastasis. The primary lesion was more advanced and the rate of incomplete resections was higher in younger patients. The incidence of cardiopulmonary complications and postoperative deaths was significantly lower in younger patients. Recurrence of the disease following complete resection was more frequent in the younger age group (chi 2 = 2.61; P = .1063), although the pattern of recurrence remained the same in both groups. Disease-free survival in younger patients following complete resection of the tumor was poorer as compared to the older patients, but the difference is statistically not significant (chi 2 = 1.882; P = .1701). These findings suggest either a delayed diagnosis or a biologically sinister disease in the younger group; further studies of the two groups vis-a-vis their biologic parameters (DNA ploidy, etc.) are in progress and will form the subject of another communication. PMID- 1619942 TI - Serum squamous cell carcinoma antigen levels in invasive squamous vulvar cancer. AB - Squamous cell carcinoma (SCC) antigen levels were studied in 34 patients with primary (N = 27) or recurrent (N = 7) SCC of the vulva. In primary disease, the SCC antigen level was greater than 2.5 ng/ml in only four patients (15%). Elevated antigen levels ranged from 2.7-18.0 ng/ml. All of these patients had advanced disease by either clinical or surgical staging systems. Four of twelve patients with inguinal metastasis had elevated SCC antigen levels. In two of these patients the inguinal nodes were abnormal to palpation. No association of the SCC level and the degree of tumor differentiation was observed. SCC antigen levels were increased slightly (2.7-4.5 ng/ml) in three of six patients with locally recurrent disease. In one patient with distant recurrence the SCC antigen was 15.3 ng/ml. In both primary and recurrent disease all elevated SCC antigen levels decreased with effective therapy. Vulvar cancer is primarily a local disease that is easily assessed by physical examination. An effective tumor marker in vulvar cancer would benefit only the rare patient with distant but not local disease. PMID- 1619943 TI - A trial of adjuvant chemoimmunotherapy with mitomycin C and OK-432 for stage III gastric carcinoma. AB - We previously found that the ability to generate cytotoxic cells induced by in vitro activation of peripheral blood mononuclear cells (PBM) with OK-432, a bacterial immunopotentiator, was markedly increased following intravenous administration of a single dose of mitomycin C (MMC) in cancer patients. On the basis of this clinical finding, we designed a treatment regimen that consisted of MMC 12 mg/m2 intravenously on day 1 and OK-432 5 Klinische Einheit (KE) intradermally on days 6, 8, and 11, when the generation of OK-432 activated killer cells had been shown to be significantly augmented. Then, it was followed by long-term tegafur. Fifteen patients with stage III gastric carcinoma who had undergone curative resection were treated with the above regimen. The survival of these patients was significantly better than that of 26 comparable stage III patients concurrently treated with MMC 12 mg/m2 alone, followed by long-term tegafur (P less than 0.01). The results indicate that OK-432 combined with MMC may be effective against stage III gastric carcinoma, when these agents are used probably in an appropriate combination. PMID- 1619944 TI - Schedule dependent inhibition of thymidylate synthase and tumor growth by 5 fluorouracil in Yoshida sarcoma bearing rats. AB - Schedule dependent inhibition of thymidylate synthase (TS) and tumor growth by 5 fluorouracil (FUra) was examined in Yoshida sarcoma (YS) bearing Donryu rats. After implantation of YS cells (1 x 10(4), FUra (20 mg/kg/day) was continuously (group C) or daily bolus injection (group B) administered for 6 days. On day 7, tumor weight was 1.57 +/- 0.58 g in group C and 0.45 +/- 0.10 g in group B (P less than 0.01), free TS was 2.23 +/- 83 fmol/mg protein in group B and 96 +/- 55 fmol/mg protein in group C (P less than 0.05), and inhibition rate of TS was 88.3 +/- 5.3% in group C and 94.7 +/- 3.0% in group B (P less than 0.05). A significant correlationship was found between free TS and tumor weight (P less than 0.05). As the next step, continuous infusion (group C) or daily bolus injection (group B) for 6 days was started on day 5 after implantation of YS cells. The relative increase of tumor on day 9 was 256 +/- 111% in group C and 112 +/- 22.1% in group B (P less than 0.05). On day 11, total TS of the resected tumor was 650 +/- 153 fmol/mg protein in group C and 391 +/- 124 fmol/mg protein in group B (P less than 0.05), and inhibition rate of TS was 78.8 +/- 12.4% in group C and 84.4 +/- 8.6% in group B. Daily bolus injection of FUra causes a superior antitumor and antimetabolic effect. The schedule dependent cytotoxicity of FUra should be taken into account when a chemotherapeutic protocol is designed. PMID- 1619945 TI - Adenocarcinoma of the urachus. AB - During the past 5 years, three patients with adenocarcinoma of the urachus were treated at our hospital. Abdominal ultrasonography helped clinch the diagnosis in all cases. All patients underwent surgical excision of the neoplasm with partial cystectomy. The clinical, radiological, and histological findings, as well as the pathogenesis of this rare neoplasm are discussed along with the surgical management. PMID- 1619946 TI - Thyroid and thymic malignancy following childhood irradiation. AB - Synchronous thyroid and thymic malignancy following childhood thymic irradiation has only been reported in two known cases previously, with a third case identified here. A rationale is presented for following these radiated patients as they age with thyroglobulin and thyroid-stimulating hormone (TSH) levels as a measure of risk of the development of nodular thyroid disease and, if such occurs, for an aggressive surgical approach. There exists a growing population at risk attributable to the success of radiation treatment of Hodgkin's and pediatric head and neck tumors. The question is raised regarding the theoretical benefits of thyroid suppressive therapy in this group at risk. With the instructive case presented, radical surgery for either thymic or thyroid carcinoma and careful monitoring for decades-late local recurrences of thymoma are suggested. PMID- 1619947 TI - Variability of HIV infections. AB - Genetic variation is the hallmark of infections with lentiviruses in general and the human immunodeficiency viruses (HIV-1, HIV-2) in particular. This article reviews both experimental evidence for the variability of the HIV genome during the course of an individual infection and mathematical models that outline the potential importance of antigenic variation as a major factor to drive disease progression. The essential idea is that the virus evades immune pressure by the continuous production of new mutants resistant to current immunological attack. This results in the accumulation of antigenic diversity during the asymptomatic period. The existence of an antigenic diversity threshold is derived from the asymmetric interaction between the virus quasispecies and the CD4 cell population: CD4 cells mount immune responses some of which are directed against specific HIV variants, but each virus strain can induce depletion of all CD4 cells and therefore impair immune responses regardless of their specificity. Therefore, increasing HIV diversity enables the virus population to escape from control by the immune system. In this context the observed genetic variability is responsible for the fact that the virus establishes a persistent infection without being cleared by the immune response and induces immunodeficiency disease after a long and variable incubation period. Mathematical biology has revealed a novel mechanism for viral pathogenesis. PMID- 1619948 TI - A selection model to estimate the interaction between food particles and the post canine teeth in human mastication. AB - Food comminution during chewing is the composite result of selection and breakage. In the selection process, every food particle has a chance of being placed between the antagonistic post-canine teeth and being subjected to subsequent breakage. The selection chance, being the ratio between the number of selected and offered particles, has been mathematically described as a function of the number of particles offered, in terms of the number of breakage sites available on the teeth and particle affinity, i.e. the fraction of breakage sites occupied by one particle. The assumption has been made that particles are successively selected during a jaw-closing phase and that the selection chance of subsequent particles having the opportunity to occupy a breakage site proportionally decreases with the unoccupied fraction of the breakage sites left. The number of selected particles of a single size then asymptotically approaches the total number of breakage sites available for that size, when the number of particles offered increases. The critical particle number, derived from the measure of particle affinity, indicates the number of particles by which the breakage sites become saturated. The selection model for single particle sizes has been successfully applied to describe one-chew experiments, using various numbers and sizes of particles made of a silicone-rubber. After pseudo-chewing movements the subjects were unexpectedly instructed to carry out a real chew on particles (half-cubes). Undamaged, hence non-selected half-cubes could afterwards be distinguished from broken particles. The model has been extended to a particle mixture to describe the selection of particles of a certain size while other particles of different sizes are present. If a two-way competition between smaller and larger particles is assumed, the model predicts that the ratios of the selection chances between different particle sizes do not depend upon the numbers of the particles in the mixture. PMID- 1619949 TI - The hypothesized hormonal control of mammalian sex ratio at birth--a second update. AB - Further evidence is adduced to support the hypothesis that the sexes of mammalian (including human) offspring are partially controlled by parental hormone levels at the time of conception. The evidence relates to variation of sex ratios at birth with (1) time of insemination within the cycle of several species, (2) excision of accessory sex glands in rodents, (3) occupation of parents, (4) dominance rating of human mothers and (5) the ordinal rank of wives in polygynous marriages. Much medical research will stem from the hypothesis if it proves to be true. (a) If it were, there would be implications for the testing of causes of many diseases: and it is noted here that the sex ratios of offspring of victims of two types of cancer (prostatic cancer and non-Hodgkin's lymphoma) are consistent with the suspected causes of these diseases. (b) There are a large number of rheumatic diseases associated with the HLA markers B 27 and B 8. These markers are apparently associated respectively with high testosterone levels in men and low testosterone levels in women. If these finding should be confirmed, a causal role for this hormone seems likely in some of these diseases. It will be interesting to examine sex ratios of relatives of probands with these diseases. PMID- 1619950 TI - An application of maximum entropy techniques to determine homogeneous sets of nucleotidic sequences. PMID- 1619951 TI - Computer modeling of gibberellin-DNA binding. AB - Computer modeling and molecular mechanics performed on the intercalation complexes of selected gibberellins or biosynthetic precursors with DNA dinucleotides revealed that under appropriate conditions the ligands insert (intercalate) between the base-paired double-stranded dinucleotide, 5'-dTdA-3'. Stabilization of the double-stranded dinucleotide after docking of a gibberellin between base pairs is inferred by the sum negative energy of hydrogen bonding and van der Waals contacts and the entropic changes which accompany the formation of each ligand-dinucleotide complex. In addition, the interactions of the gibberellins and dinucleotides, with the gibberellic acid-dinucleotide complex serving as the prototype, show optimum geometry and stereochemical hydrogen bonding recognition which are dependent upon the complementary chirality and stereochemistry of the individual components. Whether or not the gibberellins directly influence the uncoiling of DNA or gene expression at the transcriptional level via an intercalation mechanism is a matter of conjecture, albeit one that warrants intensive investigation. PMID- 1619952 TI - Models of interactions between HIV and other pathogens. AB - We investigate possible interactions between HIV and other pathogens that would arise if HIV replication were enhanced by the activation of T helper cells specific to other pathogens. Using mathematical models of the population dynamics of T helper cells, HIV and other pathogens we address three facets of the interactions between HIV and other pathogens: enhanced HIV replication due to immune stimulation by other pathogens; modified immune control of other pathogens due to immunosuppression by HIV; and the vicious circle formed by positive feedback between these two effects. The models predict that there is a correlation between higher levels of activated TH cells and disease progression and that there is a threshold number of activated TH cells above which the HIV infected immune system is unable to control pre-established pathogens. This threshold marks the boundary between a suppressed but still functioning immune system and the vicious circle of CD4 cell depletion that marks the final stages of AIDS. PMID- 1619953 TI - Markovian processes in aneuploids: I. Diploid populations. AB - The case of diploid selfing organisms which present monosomy and nullisomy for a certain pair of homologous chromosomes is considered. Three cases of dominance for fitness (i) no dominance, (ii) complete dominance and, (iii) overdominance are considered. Expressions for the average, coefficient of variation and coefficient of asymmetry for distribution which represent the number of generations needed to reach an absorbing state for a process which begins in a transient state are obtained. Expressions for the parameters are from by the application of Markov's theory of chains which was developed by Kemeny & Snell (1960, Finite Markov Chains, Princeton, NJ: Van Nostrand) and Bosso et al. (1969, Biometrics 22, 17-26). PMID- 1619954 TI - Non-planar structure of nitrous bases and non-coplanarity of Watson-Crick pairs. AB - We discuss the non-planar structural stability of the NH2-group in formamide, cytosine, adenine, guanine and aniline molecules. Based on the microwave data available on small amino derivatives and on the results of PCILO conformation study it is shown that the slope of the amino group HNH plane to the molecular plane in nitrous bases should be close to 40 degrees. One of the main consequences of the non-planar structure of bases is a comparatively large (approximately equal to 15 degrees) propeller twisting of purine and pyrimidine planes in the complementary adenine-thymine and guanine-cytosine pairs. It is concluded that the non-coplanarity of single Watson-Crick base pairs is their intrinsic property. The specificity of hydrogen bonding in pairs along with stacking is believed to be the original cause of their peculiar packing in crystals and in DNA and RNA structures. PMID- 1619955 TI - Pattern formation in one- and two-dimensional shape-space models of the immune system. AB - A large-scale model of the immune network is analyzed, using the shape-space formalism. In this formalism, it is assumed that the immunoglobulin receptors on B cells can be characterized by their unique portions, or idiotypes, that have shapes that can be represented in a space of a small finite dimension. Two receptors are assumed to interact to the extent that the shapes of their idiotypes are complementary. This is modeled by assuming that shapes interact maximally whenever their coordinates in the space-space are equal and opposite, and that the strength of interaction falls off for less complementary shapes in a manner described by a Gaussian function of the Euclidean "distance" between the pair of interacting shapes. The degree of stimulation of a cell when confronted with complementary idiotypes is modeled using a log bell-shaped interaction function. This leads to three possible equilibrium states for each clone: a virgin, an immune, and a suppressed state. The stability properties of the three possible homogeneous steady states of the network are examined. For the parameters chosen, the homogeneous virgin state is stable to both uniform and sinusoidal perturbations of small amplitude. A sufficiently large perturbation will, however, destabilize the virgin state and lead to an immune reaction. Thus, the virgin system is both stable and responsive to perturbations. The homogeneous immune state is unstable to both uniform and sinusoidal perturbations, whereas the homogeneous suppressed state is stable to uniform, but unstable to sinusoidal, perturbations. The non-uniform patterns that arise from perturbations of the homogeneous states are examined numerically. These patterns represent the actual immune repertoire of an animal, according to the present model. The effect of varying the standard deviation sigma of the Gaussian is numerically analyzed in a one-dimensional model. If sigma is large compared to the size of the shape space, the system attains a fixed non-uniform equilibrium. Conversely if sigma is small, the system attains one out of many possible non-uniform equilibria, with the final pattern depending on the initial conditions. This demonstrates the plasticity of the immune repertoire in this shape-space model. We describe how the repertoire organizes itself into large clusters of clones having similar behavior. These results are extended by analyzing pattern formation in a two dimensional (2-D) shape-space.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1619956 TI - Effect of methyl substitution on protein tertiary structure. AB - Biological effects caused by the post-translational methylation of certain side chains in proteins has been thought to be due solely to changes in charge, steric relations or hydrophobicity at the site of the methyl group. However, there is increasing evidence that the presence of CH3 can also induce a "global" effect on the protein molecule. Some of the evidence is described in this paper. PMID- 1619957 TI - Direct simulation of yeast 2-microns circle plasmid amplification. AB - The 2-microns circle is a plasmid found in most strains of the yeast Saccharomyces cerevisiae at approximately 60-100 copies per cell. The plasmid possesses the novel capacity for replicative amplification induced by site specific recombination. To address the question of whether the recombination model is adequate to account for observed rates of 2-microns circle amplification, we developed a direct computational simulation of the amplification system. Results of this simulation show that theoretically at least six copies per plasmid can be produced in each generation, and that previously unanticipated replication intermediates contribute largely to this degree of amplification. PMID- 1619958 TI - Schematic methods for probabilistic enzyme kinetics. AB - The theory of steady-state enzyme processes which avoids using the mass action law of chemical kinetics and consistently describes catalytic mechanisms by probabilistic concepts has recently been proposed (Mazur, 1991, J. theor. Biol. 148, 229-242). To facilitate the analysis of complex reaction graphs by this theory the possibility of constructing schematic rules similar to those used in classical kinetics is studied. It is found that due to the similarity of algebraic procedures the popular method of King & Altman can be applied in probabilistic kinetics in addition to the earlier proposed rule based on enumeration of cycles of the reaction graph. This similarity also allows one to adapt many other shortcut methods of classical kinetics for probabilistic reaction graphs. The paper considers separately the possibility of transforming reaction mechanisms so that the initial graph is replaced by a simpler but equivalent one. It is shown that there are few cases when a group of states can be replaced by one united state, with earlier known rules such as the rule of Cha for equilibrium stages being particular cases of a more general procedure. In addition a novel method is proposed which performs step-by-step reduction of any reaction graph. All the new methods can be adapted for traditional kinetics as well. The results obtained demonstrate that many schematic rules of classical kinetics are of probabilistic origin. PMID- 1619959 TI - An absolute rate theory model for tension control of axonal elongation. AB - This paper extends our previous thermodynamic model for the effect of mechanical force on the microtubule assembly that accompanies axonal (neurite) elongation of neurons. Based on the previous treatment, experimental data, and the formalism of absolute rate theory, we derive an exact expression for how tension on the neurite affects mechanical force in the microtubule, and in turn, how these affect the rate of microtubule assembly and neurite outgrowth in cultured neurons. This prediction approximates the experimentally observed linear relationship between growth rate and experimentally applied tension, and predicts the previously postulated three-position integral control. PMID- 1619960 TI - The insulin receptor--single function and dual effect. AB - Net effects of insulin on glucose entry, metabolism and other cellular processes have been well documented over the past 30-40 years. Although it is known that insulin binds to a specific cell membrane receptor protein which undergoes autophosphorylation and tyrosine kinase activation, the individual reactions following receptor activation that cause the metabolic changes remain unknown. It is well documented that the isolated insulin receptor has a high degree of basal autophosphorylation capacity and externally directed tyrosine kinase. There is also evidence that some in vivo autophosphorylation can take place in the total absence of insulin. If receptor activity does exist in the absence of insulin, then receptor function needs to be reanalyzed. It will be proposed here that the insulin binding membrane protein functions mainly to inhibit glucose transport under low physiological levels of insulin. Evidence of basal receptor enzymatic activity in the absence of insulin supports this theory. Under metabolically sufficient conditions, enough insulin receptors are functionally active to interact with the glucose transport system in an inhibitory manner, providing membrane control of internal glucose metabolism. Insulin acts by aggregating this inhibitory system. If inhibitory insulin receptors are aggregated following insulin elevation, their inhibitory action is prevented and glucose transport increases. This increase in transport will be in direct proportion to the temporal inhibitory level of the receptor and to the area of the cell membrane cleared of their inhibitory effect. When insulin receptor protein is confined to small areas of the cell membrane through aggregation, any potential inhibitory function is negated and glucose entry increases dramatically. This is the classical insulin effect. Both of these concepts were suggested 37 years earlier. Randle & Smith (1957, Biochem. Biophys. Acta 25, 442; 1958, Biochem. J. 70, 490) proposed that the internal supply of energy rich compounds limited glucose entry and that the effect of insulin was to inhibit this process which was inhibiting glucose entry. The present report provides a mechanism for this. PMID- 1619961 TI - Stimulated and co-operative electron transfer in energy conversion and catalysis. AB - A new mechanism of electron transfer, stimulated electron transfer, is postulated, in which an electronic feedback is drastically increasing both the rate of electron transfer and the propagation of free energy along electron transferring molecular pathways. In principle, the idea of pushing a system far from equilibrium to achieve a high reaction rate and co-operative phenomena is applied to molecular electron transfer. The effect is calculated from a semiclassical kinetic model of a chain redox reaction with autocatalytic feedback on individual rate constants, where the steps have subsequently been minimized to obtain a continuous electron transfer pathway with electronic feedback. The influence of inhomogeneities and asymmetries in the electron transfer path and of vectorial components (electrical field, gradient of redox potential) are discussed as well as the acceleration of individual and multiple electron transfer as a function of feedback. Examples of autocatalytic feedback are provided including mechanisms involving electron transfer proteins and multi centre electron transfer catalysts. Such a phenomenon can be described for molecular and interfacial electron transfer in analogy to stimulated and coherent light emission. The results suggest that autocatalytic or stimulated electron transfer may be a key to the understanding of efficient electron transfer and co operative multi-electron transfer catalysis in biology and a challenge for fuel production mechanisms in artificial photosynthesis and fuel cycles. PMID- 1619962 TI - Human disease mortality kinetics are explored through a chain model embodying principles of extreme value theory and competing risks. AB - The distributions for human disease-specific mortality exhibit two striking characteristics: survivorship curves that intersect near the longevity limit; and, the clustering of best-fitting Weibull shape parameter values into groups centered on integers. Correspondingly, we have hypothesized that the distribution intersections result from either competitive processes or population partitioning and the integral clustering in the shape parameter results from the occurrence of a small number of rare, rate-limiting events in disease progression. In this report we initiate a theoretical examination of these questions by exploring serial chain model dynamics and parameteric competing risks theory. The links in our chain models are composed of more than one bond, where the number of bonds in a link are denoted the link size and are the number of events necessary to break the link and, hence, the chain. We explored chains with all links of the same size or with segments of the chain composed of different size links (competition). Simulations showed that chain breakage dynamics depended on the weakest-link principle and followed kinetics of extreme-values which were very similar to human mortality kinetics. In particular, failure distributions for simple chains were Weibull-type extreme-value distributions with shape parameter values that were identifiable with the integral link size in the limit of infinite chain length. Furthermore, for chains composed of several segments of differing link size, the survival distributions for the various segments converged at a point in the S(t) tails indistinguishable from human data. This was also predicted by parameteric competing risks theory using Weibull underlying distributions. In both the competitive chain simulations and the parametric competing risks theory, however, the shape values for the intersecting distributions deviated from the integer values typical of human data. We conclude that rare events can be the source of integral shapes in human mortality, that convergence is a salient feature of multiple endpoints, but that pure competition may not be the best explanation for the exact type of convergence observable in human mortality. Finally, while the chain models were not motivated by any specific biological structures, interesting biological correlates to them may be useful in gerontological research. PMID- 1619963 TI - Study of the relationship between estimates of enzyme kinetic parameters. AB - Previous indications of an intrinsic relationship between estimates of Km and Vmax calculated from the Michaelis-Menten equation have been explored further. A mathematically linear relationship could be established for the estimates of the two parameters. The relationship--the trend line--holds whether or not the experimental error is linked to the rate of reaction, the substrate concentration or both, provided that the distribution of errors is symmetrical. The practical implication is that enzyme variants with low values of Km and Vmax may not be distinguishable from those with high values of Km and Vmax. PMID- 1619964 TI - Gaps in the erythrocyte membrane skeleton: a stretched net model. AB - The geometry of spectrin-free regions in the erythrocyte membrane skeleton is modeled using Monte Carlo calculations for an incomplete triangular lattice of entropy springs under tension. Intact springs correspond to normal spectrin molecules, and cut springs correspond to spectrin that is missing or unable to associate normally. As springs are cut and the network is allowed to relax to mechanical equilibrium, gaps in the network appear. Geometrical properties of these gaps are obtained as a function of the fraction of springs cut. The most important property modeled is the area of the largest spectrin-free region; this area increases approximately exponentially as the fraction of normal spectrin decreases from 100% to approximately 50%. The effect of these gaps on lateral diffusion and vesiculation is discussed. PMID- 1619965 TI - The discovery of DuP 753, a potent, orally active nonpeptide angiotensin II receptor antagonist. PMID- 1619966 TI - Strain differences in regional brain histamine levels between genetically epilepsy-prone and resistant rats. AB - In order to further elucidate the possible role of histamine in the seizure model, we determined the histamine levels in different brain regions of genetically epilepsy-prone Krushinski-Molodkina (KM) rats. Histamine levels in the striatum, hippocampus, amygdala, midbrain, thalamus and hypothalamus of KM rats were significantly lower than in the epilepsy-resistant Wistar rats. Previously, we have reported that the audiogenic seizures of KM rats were reduced by metoprine, which can markedly increase brain histamine. These findings are in agreement with the hypothesis that central histamine neuron system may be involved in the inhibitory mechanism of seizures. PMID- 1619967 TI - Effect of aging on the renin angiotensin system in patients with renovascular hypertension. AB - The effect of aging on the renin angiotensin system (RAS) was studied in 30 patients with renovascular hypertension and 33 patients with essential hypertension. Plasma renin decreased with age in patients with renovascular hypertension and essential hypertension. However, in patients with renovascular hypertension, the change was not statistically significant. Plasma aldosterone concentration showed a tendency to decrease with age in both groups. Stimulated plasma renin activity and the net increase in plasma renin activity after captopril administration in patients with essential hypertension showed a significant decrease with age. In patients with renovascular hypertension, exaggerated response of renin secretion was observed in younger patients, but middle-aged and elderly patients did not demonstrate this hyper-responsiveness. The degree of decrease in blood pressure by administration of an angiotensin (Ang) II analog ([Sar1,Ile8] Ang II) was the same in both younger and elderly patients with either disease. These results suggest that the effect of aging on the RAS occurs not only in patients with essential hypertension, but also in patients with renovascular hypertension. Furthermore, although the Ang II analog infusion test and captopril stimulation test are considered to be useful screening tests for renovascular hypertension, we consider that the combination of Ang II analog test and captopril test may be favorable to screen renovascular hypertension, since the captopril stimulation test had a lower sensitivity in younger (under 35 years old) patients. PMID- 1619968 TI - Comparative pharmacokinetics of propofol in Chinese adults and children. AB - The pharmacokinetics of propofol were studied in 14 healthy young male Chinese adults, aged 18-38 years, undergoing minor orthopedic surgery. All patients who received a single bolus dose of propofol 2.5 mg/kg were paralyzed with atracurium and mechanically ventilated. Anesthesia was maintained with 67% nitrous oxide plus 1-2% isoflurane in oxygen with alfentanil 5 micrograms/kg intravenously as a bolus injection. Blood concentrations of propofol over the subsequent 24 hours were measured using high pressure liquid chromatography with fluorimetric detection. Data were consistently described by a three compartment model but analysis revealed two significantly different blood propofol concentration-time profiles (p less than 0.05). Five patients, designated "fast" metabolizers, demonstrated a mean elimination half-life which was shorter than that described in Chinese children, while their total body clearance was similar. Nine other patients, designated "slow" metabolizers, had a longer mean elimination half-life and slower total body clearance than those in elderly Caucasian patients. This may be suggestive of propofol metabolism at some extra-hepatic site in some patients, while other patients demonstrate marked lipophilicitic constraint of the drug by the deep compartment. PMID- 1619969 TI - Injections of kainic acid into the raphe dorsal nucleus in freely moving cats: electroencephalographic, behavioral and histopathological consequences. AB - Results are presented concerning the functional and morphological changes occurring after kainic acid injections into raphe dorsal nucleus in freely moving cats. The effects of kainic acid at two doses, 4 and 12 nmol, on electroencephalographic activity, behavior and cell morphology were examined on the day of injection, and on the 1st, 3rd, 6th, 15th, 30th and 65th day. A well pronounced dose-dependent effect of kainic acid was established: in 50% of the animals injected with 4 nmol of kainic acid and in 85.7% of the animals injected with 12 nmol electroencephalographic and behavioral seizures appeared. The strength of the seizures in the animals receiving 12 nmol of kainic acid was different--from focal single epileptiform patterns first in raphe dorsal nucleus and then in other brain regions to generalized high-voltage ictal activity and in some animals to epileptic state. In all animals receiving 4 nmol of kainic acid and in 75% of the animals receiving 12 nmol of kainic acid, the electrical activity and behavior returned to normal several hours after or within two days following the kainic acid injection. The histopathological data obtained by light microscopy showed a dose-dependent cytoarchitectural disorganization (mainly chromatolytic changes) not only at the injection site but also in many other brain structures. The present results confirm our previous studies on cats in acute conditions showing enhancement of brain excitability level up to hyperexcitation (seizures) after kainic acid injection into the raphe dorsal nucleus. PMID- 1619970 TI - Modulation of glucose homeostasis by doxepin. AB - Blood glucose level (BGL) was estimated up to 4 h (3 h in case of GTT) in 18-h fasted albino rabbits following acute and chronic (one month) feeding of doxepin and thereafter for another 8 days together with either insulin or glibenclamide or adrenaline. A single dose of doxepin produced significant hypoglycemia which peaked at 4 h and lasted up to 10 h. On chronic doxepin feeding there was complete attenuation of initial hypoglycemia on the 7th and 14th days, culminating into frank hyperglycemia on the 21st day. However, there was complete recovery on the 29th day exhibiting tolerance to initial hypo-as well as delayed hyperglycemia. Similarly, glucose intolerance was accentuated on the 8th day followed by a gradual recovery on the 15th and 22nd days, culminating in disappearance of glucose intolerance on the 30th day. The hypoglycemic effect of insulin was markedly potentiated in chronically doxepin fed animals which was further enhanced on continuing administration of both agents. Profound hypoglycemia was observed during GTT in such animals. The hyperglycemic effect of adrenaline was enhanced in chronically doxepin fed animals, which may be due to TCA induced enhancement of the response of exogenous adrenaline. Suppression of this hyperglycemia with continued administration of both drugs seems to be due to subsensitivity of alpha 2-adrenoceptors. Additive hyperglycemia was observed during GTT in such animals. PMID- 1619971 TI - [Control of exocrine pancreatic secretion--which mediators are more important: nerves or hormones?]. PMID- 1619972 TI - [Effect of pancreatic innervation on exocrine secretory performance of the pancreas]. AB - In the present study we examined the influence of extrinsic pancreatic innervation on exocrine pancreatic response to secretin, caerulein, tryptophan and fat, and furthermore the amino acid- and fat-stimulated release of neurotensin and CCK in dogs. Denervation of the pancreas did not alter secretory response to secretin and caerulein, whereas transsection of the extrinsic nerves significantly diminished the protein response to tryptophan and fat. Release of CCK was not altered by pancreatic denervation. However, fat-evoked neurotensin plasma levels were significantly increased after denervation of the pancreas. PMID- 1619973 TI - [Massive gastrointestinal hemorrhage from a hepaticojejunostomy in pancreatogenic mesenteric vein thrombosis. Diagnosis and therapy]. AB - Gastrointestinal hemorrhage in a patient with a biliodigestive anastomosis necessitates exclusion of a bleeding source in the region of the choledocho- or hepaticojejunal anastomosis. This cannot be achieved by endoscopic methods. The source of bleeding can sometimes, though rarely, be localised by performance of selective angiography during hemorrhage. Laparotomy with exploration of the anastomosis during such an episode is at the same time a diagnostic and a therapeutic intervention. The surgical procedure of choice is de-anastomosis, resection of the bypassed jejunal loop and formation of a hepatico-duodenostomy. PMID- 1619974 TI - [Changes in liver function and morphology after various portocaval bypass operations]. AB - Using an experimental animal model consequences of operatively changed modes of liver perfusion on hepatic function could be demonstrated. Three groups of 5 animals each (swine) had the following operations: Group I received a portocaval shunt. In group II in addition to the portocaval shunt a vein graft was interposed between the vena cava and the portal vein. In group III an arterialization of this graft was performed in addition to the two operations mentioned above. Follow-up at defined time intervals included clinical, laboratory and histological data. It could be demonstrated that animals in group II and III showed normal parameters as far as behavior and controlled lab data are concerned. Animals of group I had significantly poorer results in all tests. In this study we found that direct portal perfusion was not necessary for a normal liver function and could be fully compensated both by caval venous blood and by arterialized caval venous blood. PMID- 1619975 TI - [Exulceratio simplex Dieulafoy]. AB - "Exulceratio simplex Dieulafoy" is a rare cause of massive upper gastrointestinal haemorrhage from a submucosal artery. Dieulafoy's disease is rarely recognized. We present 9 cases of Dieulafoy's lesion and have collected 176 cases described in the literature. PMID- 1619976 TI - [Cystic parathyroid gland adenomas: pathologic-anatomic variants of parathyroid gland adenomas or a separate disease entity?]. AB - Between 01.01.1987 and 31.12.1990 a primary operation was performed on 126 patients in the Dept. of General Surgery, University of Marburg Hospital for primary hyperparathyroidism due to a parathyroid adenoma. Their clinically relevant data were prospectively documented. In 6 patients (4.8%) a total of 7 cystic parathyroid adenomas was found. While there was no difference in age- and sex-distribution, patients with cystic adenomas were found to have markedly higher serum parathormone and alkaline phosphatase levels than patients with solid adenomas. Calcium levels were similar in both groups. Cystic adenomas were much heavier than solid adenomas. A significant number of cystic adenomas was found to be displaced into the posterior mediastinum. The property of cystic parathyroid adenomas to be frequently located away from their usual anatomical position can make the intraoperative search for them difficult. PMID- 1619977 TI - [The value of clinical, laboratory and sonographic findings in acute appendicitis -effect of surgical experience and bacteriologic diagnosis on the rate of wound healing disorders]. AB - A total of 361 patients were admitted to the Department of Surgery of the University of Heidelberg between January 1989 and April 1990 for acute appendicitis. Neither the physical examination nor laboratory results were unequivocally diagnostic in a third of the patients. The ultrasonographic visualization of the inflamed appendix could confirm the diagnosis in 50% of the clinically doubtful cases (predictive value: 84%). Further diagnostic procedures were rarely necessary. The perforation rate was independent of the duration of the preoperative hospitalization due to the rapid surgical treatment. Contrary to previous reports, the likelihood of an intraoperatively innocent appendix increased with delayed surgery. Wound infection rates were similar after appendectomies by surgeons in training and by fully qualified surgeons although perforated appendices were typically removed by the latter ones. Antibiotic therapy was usually administered for severely inflamed appendices depending on the intraoperative findings and for perforated appendices and reduced the rate of wound infections if more than two bacteria had been cultured from a routine intraoperative swab. The documentation used in Baden-Wurttemberg for quality control should include the result of an intraoperative appendiceal swab. PMID- 1619978 TI - [The long-term prognosis of breast cancer. Retrospective study of 973 patients]. AB - In this study the outcome after 40 years of primary breast cancer therapy was analysed. 973 patients admitted between 1943-1964 were examined. At the time of evaluation 900 (92.5%) of these patients were deceased. The mean survival time was 7.02 years. Tumor stage was the most important prognostic factor. In stage I patients after 40 years 17% of the patients were still alive. In stage II patients the prognosis was significantly worse. After 3.5 years 50% of the patients were dead. Young patients under 40 years of age showed a significantly lower survival rate during the first 5 years after therapy. The histological type did not show any influence on the outcome. In 91.5% of all patients a radical mastectomy was performed. Therefore the different operative procedures can not be compared in this study. 560 patients received postoperative adjuvant radiotherapy. Patients with radiotherapy showed a higher survival rate only during the first 5 years. After this time the survival rate of patients with radiotherapy was significantly lower. This was found already after 2 years in stage I patients. 85% of the deceased patients died with or because of breast cancer. 98.2% of breast cancer related deaths were observed during the first 10 years. After 26 years no breast cancer death was observed. Considering the 7.5% surviving patients at least 22% of the breast cancer patients did not show a breast cancer recurrence over the 40 year period. This demonstrates that the biological characteristics of breast cancer can not be explained by the theory of B. Fisher or the Halsted theory alone. PMID- 1619979 TI - [Effect of cecostomy on the pathophysiology and prognosis of acute experimental pancreatitis]. AB - In 76 male wistar rats with a median weight of 340 g acute pancreatitis was induced by injection of 2% sodium taurocholate into a temporarily closed duodenal loop. 40 animals received an additional cecostomy (group B), the others served as controls (group A). The postoperative figures for amylase, leucocyte count, and hemoglobin were nearly identical in both groups. According to histologic criteria acute pancreatitis was comparable in both groups, too. In nine rats endotoxin was found elevated postoperatively (13.4%). Seven animals belonged to the control (22.6%) and only two to the cecostomy group (5.6%). The difference was statistically significant (p less than 0.05). Also the differences between the median serum endotoxin levels reached statistic significance (79 ng/l in group B vs. 219 ng/l in group A). Mortality was significantly increased in endotoxin positive animals (42.9% vs. 19.4%). Additionally, among the animals of the control group alterations of the colonic mucosa were observed more frequently than in the cecostomy group. The results are in favour of a translocation of endotoxin from the gut lumen into the circulation during acute experimental pancreatitis. PMID- 1619980 TI - [The effect of taurolin on endogenous immunity and pathogen elimination in human peritonitis]. AB - The influence of taurolin on phagocytosis-related defense functions and on the elimination of bacteria has been investigated in a controlled study. Particle opsonisation, a prerequisite for sufficient phagocytosis, was undisturbed in presence of up to 0.1% taurolin. Intraabdominal taurolin application did not diminish the leukocyte influx into the abdominal cavity. Opsonic capacity of peritoneal exudate was low in the taurolin group. These exudates contained more severe bacterial contamination, suggesting that this deficit was due to enhanced specific consumption of opsonins. Taurolin treatment resulted in a marked reduction of bacterial growth. Thus the substance provides antiseptic capacities without afflicting the physiological defense systems. PMID- 1619981 TI - [Esophagojejunoplication with the stapler technique. Results of a controlled study]. PMID- 1619982 TI - Host and tissue tropism of hepatitis B virus. PMID- 1619983 TI - A method for sequential excision biopsies of rat liver in an isolated perfused system. AB - We describe a simple method of performing sequential excision biopsies during liver reperfusion in the isolated perfused rat liver. After hepatectomy, four ligatures (5.0 silk) tied with a slip knot are placed around the pedicles of: (1) the inferior and (2) the superior parts of the caudate lobe, as well as (3) the inferior and (4) the superior parts of the right lateral lobe. At the time of biopsy, the prepared 5.0 silk ties are tightened with sufficient force to occlude the vascular pedicle, preventing leakage of circulating perfusate. The procedure provides four biopsies of more than 350 mg each without alteration of perfusate transaminases and tissue ATP contents. The total tissue removed by this method comprises 20-25% of the whole liver weight. PMID- 1619984 TI - Role of septal fibrosis in development of hepatic circulatory disturbance in the presence of liver cell enlargement. AB - The effect of septal fibrosis on hepatic circulation was examined in rats with enlarged liver cells. Septal fibrosis was produced by horse serum injections and liver cell enlargement by a choline-deficient diet. Septal fibrosis alone did not induce any disturbance of hepatic circulation. In fatty livers, a slight increase in sinusoidal vascular resistance and a slight elevation of portal vein pressure were found. However, in fatty livers with septal fibrosis, portal hypertension and sinusoidal vascular resistance were higher than in fatty livers without septal fibrosis. These experimental data clearly demonstrate that septal fibrosis alone has no effect on hepatic circulation, but septal fibrosis in the presence of liver cell enlargement markedly affects sinusoidal circulation and induces portal hypertension. The augmentation of sinusoidal vascular resistance by septal fibrosis in the presence of liver cell enlargement might be due to the severe deformation of the sinusoids by enlarged liver cells in the limited spaces surrounded by septal fibrous bands. PMID- 1619985 TI - The effect of ephedrine/caffeine mixture on energy expenditure and body composition in obese women. AB - Treatment with beta 2-agonists promotes fat loss and muscle growth in numerous species, but human studies are lacking. We studied the effect of a compound with beta 2-agonistic properties (ephedrine 20 mg/caffeine 200 mg [E + C]). Fourteen obese women were treated with a 4.2-MJ/d diet and either E + C or placebo (P) three times per day for 8 weeks in a double-blind study. Weight-loss was not different in the groups, but the E + C group lost 4.5 kg more body fat and 2.8 kg less fat-free mass (FFM). The decrease in 24-hour energy expenditure (EE) seen in the P group was 10% at day 1 and 13% at day 56, but was only 7% and 8% in the treated group (P = .044). The higher EE in the E +C group was entirely covered by fat oxidation. These findings provide evidence that promotion of fat loss and preservation of FFM during weight reduction may also be achieved pharmacologically in humans. PMID- 1619986 TI - Reversal of steroid-induced insulin resistance by a nicotinic-acid derivative in man. AB - A recent report suggested that the glucose-free fatty acid (FFA) cycle may contribute to steroid-induced insulin resistance in rats, and that glucose tolerance could be restored to normal when FFA levels were lowered with nicotinic acid. To test this hypothesis in man, we measured insulin sensitivity (by euglycemic insulin clamp in combination with indirect calorimetry and infusion of tritiated glucose) before and after short-term administration of a nicotinic-acid derivative (Acipimox) in 10 steroid-treated, kidney transplant patients with insulin resistance. Thirty-five healthy subjects served as controls. Six of them received Acipimox. Total body glucose metabolism was reduced in steroid-treated patients compared with control subjects (41.7 +/- 3.3 v 50.0 +/- 2.2 mumol/kg lean body mass [LBM].min, P less than .05). The reduction in insulin-stimulated glucose uptake was mainly due to an impairment in nonoxidative glucose metabolism (primarily glucose storage as glycogen) (18.3 +/- 2.8 v 27.2 +/- 2.2 mumol/kg LBM.min, P less than .01). Acipimox lowered basal FFA concentrations (from 672 +/ 63 to 114 +/- 11 mumol/L, P less than .05) and the rate of lipid oxidation measured in the basal state (1.5 +/- 0.2 to 0.6 +/- 0.1 mumol/kg LBM.min, P less than .01) and during the clamp (0.7 +/- 0.2 to 0.03 +/- 0.2 mumol/kg LBM.min, P less than .05). In addition, Acipimox administration normalized total glucose disposal (to 54.4 +/- 4.4 mumol/kg LBM.min), mainly due to enhanced nonoxidative glucose metabolism (to 28.9 +/- 3.9 mumol/kg LBM.min) in steroid-treated patients (both P less than .05 v before Acipimox).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619987 TI - Influence of omega-3 fatty acids on splanchnic blood flow and lactate metabolism in an endotoxemic rat model. AB - Alteration in regional blood flow is important in the pathogenesis of organ failure during endotoxemia and sepsis. In particular, intestinal ischemia is thought to enhance the translocation of bacteria into the systemic circulation. We used radioactive microspheres to measure the influence of two intravenous (IV) dietary fats (vegetable oil containing high levels of omega-6 fatty acids, and fish oil containing high levels of omega-3 fatty acids) on regional blood flow during low-dose Escherichia coli endotoxin infusion (0.1 mg/100 g body weight [BW]) in a rat model. Despite absence of changes in the cardiac output, blood flow rates to the small and large intestines, stomach, and pancreas, and also to the skin and skeletal muscle were significantly reduced after 18 hours of endotoxin infusion in the rats fed standard vegetable oil. Short-term IV feeding during a period of 40 hours with an isonitrogenous, isocaloric nutrient solution containing fish oil as the only lipid source normalized intestinal perfusion and increased blood flow to the liver and spleen. Low-dose endotoxin infusion also resulted in significant increases in glucose, lactate, and pyruvate concentrations. In comparison to standard vegetable fat emulsion, fish oil significantly reduced these parameters. A second experiment was conducted to measure lactate kinetics. Based on the dilution of U-14C-lactate, fish oil feeding was associated with higher lactate clearance than standard vegetable oil feeding during the endotoxin infusion. We conclude that short-term IV feeding with fish oil improves intestinal perfusion and portal blood flow, improves glucose tolerance, and increases lactate clearance in a low-dose endotoxin rat model. PMID- 1619988 TI - Time course of plasma free fatty acid concentration in response to insulin: effect of obesity and physical fitness. AB - This study examines the relationships between parameters of the time course of plasma free fatty acid (FFA) concentration during a euglycemic, hyperinsulinemic clamp (100 mU/m2.min) and the age, body composition, and physical fitness, indexed as maximal aerobic capacity (VO2 max), of three groups of healthy men: (A) 20 obese older men (32% +/- 1% fat, aged 60 +/- 2 years, mean +/- SEM); (B) 11 lean older men (19% +/- 1% fat, aged 63 +/- 2 years); and (C) 11 lean younger men (16% +/- 2% fat, aged 27 +/- 2 years). The time course was modeled as a delayed exponential decline from an initial level to a plateau level. The plateau level was 72% +/- 2%, 72% +/- 2%, and 68% +/- 3% of the initial level in groups A, B, and C, respectively. The delay was shorter in the younger men than in the older men (7.6 +/- 0.9 minutes in group C v 13.2 +/- 1.0 in group A and 11.9 +/- 1.6 minutes in group B), but correlated more strongly with percent fat, waist to hip ratio (WHR), or VO2max than with age. The magnitude of the rate constant of the exponential, k, was smaller in obese than in lean men (3.2 +/- 0.2 h-1 in group A v 5.3 +/- 0.6 h-1 in group B and 6.4 +/- 0.6 h-1 in group C), and was independently predicted only by percent fat in the older men and only by VO2max when the older and younger groups were combined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619989 TI - Regional cerebral blood flow in normal man during insulin-induced hypoglycemia and in the recovery period following glucose infusion. AB - The effect of moderate hypoglycemia (p-glucose, 2.0 +/- 0.3 mmol/L; mean +/- SD) on regional cerebral blood flow (rCBF) was studied in a group of 10 healthy, right-handed men (aged 23 to 28 years) using an intravenous xenon 133 single photon emission computed tomography technique (SPECT). After 10 minutes of hypoglycemia, global CBF had increased to 46.3 +/- 9.6 mL/100 g/min compared with the initial normoglycemic flow of 38.6 +/- 6.8 mL/100 g/min (P less than .01). The relative distribution of the rCBF changed significantly (P less than .05, ANOVA) from before to during hypoglycemia. Of the 10 regions analyzed, the highest increments in rCBF during hypoglycemia were found in the frontal (21.5% +/- 15.2%) and parietal (20.6% +/- 14.2%) lobes, and the lowest (10.7% +/- 9.4%) were found in the pons/brainstem regions. The increase in rCBF persisted for 15 minutes after normalization of blood glucose. The persisting high flow after hypoglycemia affected all regions, but a further 10.1% +/- 7.2% increase was observed in the pons/brainstem area (P less than .05). The CBF was significantly higher in the right compared with the left hemisphere (2.8%, 1.2%, and 3.9%, respectively; P less than .05) in all measurements. A decrease in brain volume was found at the final examination, compared with the hypoglycemic state (2.6%; P less than .05). It is concluded that moderate hypoglycemia leads to a marked increase in CBF and in the relative distribution of rCBF, which persists in the immediate period after normalization of the blood glucose level. PMID- 1619990 TI - Metabolic changes during early starvation in rats fed a low-protein diet in the postweaning growth period. AB - Metabolic changes during the first 24 hours of starvation were studied in rats previously adapted for 3 weeks during the postweaning growth period to a low protein diet using lactalbumin as a dietary protein source. Previous adaptation to a high-quality, low-protein diet reduced the effects of early starvation on the loss of body and liver weight. In rats fed a low-protein diet (6% lactalbumin, LP rats), free triiodothyronine (T3) concentration remained higher than in control rats (13% lactalbumin, C rats) throughout the experiment (+38%, 24 hours), and the plasma insulin concentration, which was lower than in C rats during the first 6 hours (-56%), was not different thereafter. Plasma insulin to glucagon molar ratio was lower (-54%) and liver cyclic adenosine monophosphate (cAMP) concentration was higher (+28%) in LP than in C rats in the fed state, but these were not different at 24 hours of starvation. Plasma glucose concentration was slightly lower in LP than in C rats (-15%) in the fed state, but it was not different in both groups during starvation. Whereas they were unchanged in the fed state, plasma lactate concentration was lower (-57%) and free fatty acid and total ketone body concentrations were higher (+38% and +183%, respectively) in LP than in C rats at 24 hours of starvation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619991 TI - Effects of growth hormone administration on fuel oxidation and thyroid function in normal man. AB - In a randomized, double-blind, placebo-controlled, cross-over study, we examined the effects of 14 days of growth hormone (GH) administration (12 IU/d subcutaneously) on energy expenditure (EE), respiratory exchange ratio (RER), and thyroid function in 14 normal adults of normal weight (eight men and six women). EE (kcal/24 h) was significantly elevated after GH administration (2,073 +/- 392, [GH], 1,900 +/- 310, [placebo], P = .01). RER was significantly lowered during GH administration (0.73 +/- 0.04 v 0.78 +/- 0.06, P = .02), reflecting increased oxidation of lipids. Total triiodothyronine (TT3) (nmol/L) and free T3 (FT3) (pmol/L) increased significantly during GH (TT3: 1.73 +/- 0.06 [GH], 1.48 +/- 0.08 [placebo], P = .01; FT3: 6.19 +/- 0.56 [GH], 5.49 +/- 0.56 [placebo], P = .01). Concomitantly, an insignificant decrease in reverse T3 (rT3) (nmol/L) was observed (0.07 +/- 0.01 [GH], 0.15 +/- 0.01 [placebo], P = .08). GH caused a highly significant increase in T3/thyroxine (T4) (x 100) ratio (1.84 +/- 0.12 [GH], 1.37 +/- 0.06 [placebo]). Serum thyrotropin (TSH) was not significantly changed by GH. No changes in total thyroxine (TT4) (nmol/L) (98 +/- 6 [GH], 111 +/- 8 [placebo], P = .40) and free thyroxine (FT4) (pmol/L) (17.4 +/- 1.3 [GH], 18.6 +/- 1.1 [placebo], P = .37) after 14 days of GH administration were observed. In conclusion, 2 weeks of GH administration increases EE and lipidoxidation. This finding may partly be mediated by an increase in peripheral T4 to T3 conversion. PMID- 1619992 TI - Effect of human growth hormone (GH)-binding protein in human serum on GH binding to rabbit liver membranes. AB - The sequence identity of growth hormone-binding protein (GH-BP) with the extracellular domain of GH receptors raised the possibility that circulating GH BP might affect the binding of human GH (hGH) to its receptors, and thus, its biological effects. To test this hypothesis, we tested the effects of sera with low GH-BP levels (obtained from prepubertal children, girls with anorexia nervosa [AN], and patients with hepatic cirrhosis), normal control sera, and sera with high GH-BP levels (obtained from obese patients) on hGH binding to its receptors. GH-BP activity in patients' sera was measured by incubation with [125I]hGH and the separation of bound hGH from free hGH with dextran-coated charcoal. The effect of GH-BP was studied by preincubation of patients' sera with increasing concentrations of hGH, followed by incubation with [125I]hGH and a rabbit liver membrane preparation known to be rich in GH receptors, and finally by measuring hGH bound to the receptors. In this study, we report on the ability of GH-BP to reduce the inhibitory capacity (IC50) of hGH on [125I]hGH binding to GH receptors. The concentration of GH-BP in serum is positively correlated with the IC50 of hGH incubated with different sera on [125I]hGH binding to its receptors (n = 21; r = .886, P less than .001). In the presence of high serum GH-BP levels, such as those observed in obesity (20.13% +/- 0.71%/0.05 mL serum), the IC50 values were significantly higher than those obtained with sera containing GH-BP levels lower than those measured in human control subjects, such as from prepubertal children, AN patients, and cirrhotic patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619993 TI - Total energy expenditure and energy requirements in healthy elderly persons. AB - To investigate energy requirements in healthy elderly subjects, we assessed the association of total energy expenditure (TEE) with resting metabolic rate (RMR), physical activity, body composition, and energy intake in 13 individuals (aged 56 to 78 years, six women and seven men). Free-living TEE was measured using doubly labeled water, RMR was measured by respiratory gas analysis, and energy expenditure of physical activity (EEPA) was derived from the difference between TEE and RMR, assuming the thermic response to feeding contributes 10% of TEE. Fat mass (FM) and fat-free mass (FFM) were obtained from underwater weighing, VO2max was determined from a bicycle test to exhaustion, energy intake was obtained from a 3-day food diary, and leisure time activity (LTA) was determined by structured interview. TEE was 2,406 +/- 438 kcal/d (range, 1,856 to 3,200 kcal/d, or 1.25 to 2.11 times RMR) and was related to VO2max (r = .79, P = .001), LTA (r = .74, P = .004), FFM (r = .69, P = .009), and FM (r = -.64, P = .018). The association between TEE and VO2max persisted after adjustment for FFM (partial r = .58, P = .036). EEPA was related to LTA (r = .83, P less than .0001) and FM (r = -.58, P = .039). Energy intake underestimated TEE by 31% +/- 18% in women and by 12% +/- 11% in men. Using stepwise regression, TEE was best predicted by VO2max and LTA (total adjusted r2 = .86). We conclude the following: (1) TEE varies greatly within healthy elderly subjects due to variations in physical activity; (2) VO2max has an important role in predicting energy requirements in older individuals; and (3) healthy older individuals underreport energy intake. PMID- 1619994 TI - Reliability of the measurement of postprandial thermogenesis in men of three levels of body fatness. AB - To determine the reliability of the measurement of postprandial thermogenesis by indirect calorimetry and to clarify further the relationship of obesity to thermogenesis in men, the thermic effect of a 720-kcal, mixed liquid meal was compared in 13 lean men (mean +/- SEM, 11.2% +/- 1.4% body fat), 10 average men (22.4% +/- 1.6% body fat), and 12 obese men (33.4% +/- 1.6% body fat) on two occasions. Resting metabolic rate (RMR) was measured for 3 hours: (1) in the fasted state, and (2) after a 720-kcal mixed liquid meal, on two occasions. The thermic effect of the meal, calculated as the postprandial energy expenditure minus the fasting RMR (kcal/3h), was greater for the lean and average men than for the obese men during both trials (P less than .001), but was only marginally different between the lean and average groups (P = .16). The mean values for the two trials were similar and the measurement of thermogenesis was highly reproducible with a reliability coefficient of r = .932 (P less than .001). Across all groups, thermogenesis correlated strongly with percent body fat (r = .64, P less than .01), but within the average men, thermogenesis was uncorrelated with percent body fat (r = .09) but highly correlated with the glucose response to the meal (r = -.75, P less than .05). Thus, factors other than body fatness, such as insulin sensitivity, may determine thermogenesis within this heterogeneous middle group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619995 TI - The role of the opioid peptides in the development of hyperinsulinemia in obese women with abdominal body fat distribution. AB - In this study, we investigated the hypothesis that increased opioid activity may be involved in the development of hyperinsulinemia in women with obesity and abdominal body fat distribution. Two groups of nine obese body (body mass index [BMI], 30 to 40 kg/m2) women with abdominal (A-ob) (waist to hip ratio [WHR] greater than 0.85) or gluteo-femoral (F-ob) (WHR greater than or equal to 0.80) fat distribution were examined and compared with eight normal-weight controls. Basal beta-endorphin levels were higher in the A-ob group than in the other groups. Each woman underwent two oral glucose tolerance tests (OGTT, 75 g glucose). A bolus of naloxone (0.8 mg) followed by a constant infusion of naloxone (0.04 mg/kg/h) or saline was also administered during the glucose challenge in random order, and blood samples for glucose, insulin, and C-peptide were collected at regular times after glucose administration. No difference was observed in basal or stimulated glucose concentrations between the three groups, nor between the saline or naloxone study. However, basal and stimulated insulin levels were significantly higher in obese women (particularly in the A-ob group) than in controls. Naloxone administration, however, did not significantly modify insulin and C-peptide glucose-stimulated concentrations in controls and in the F ob group, whereas it significantly reduced (by approximately 47%) insulin levels in the A-ob group. Partial correlation coefficients showed a significant negative correlation between percent variation of glucose-stimulated insulin incremental areas during the naloxone study and the WHR in all women considered together (r = .544, P less than .025).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619996 TI - The effects of chromium supplementation on serum glucose and lipids in patients with and without non-insulin-dependent diabetes. AB - Seventy-six patients with established atherosclerotic disease were treated daily with either 250 micrograms of chromium orally as chromium chloride or a placebo for a period of 7 to 16 months (mean, 11.1 months). Serum chromium increased from 2.69 +/- 0.09 to 12.12 +/- 0.77 nmol/L (mean +/- SE, P less than .005). Serum triglycerides were lower (1.68 +/- 0.11 and 2.10 +/- 0.14 nmol/L, respectively; P less than .02) in the chromium-treated patients than in the patients who received placebo, and serum high-density lipoprotein (HDL) increased (from 0.94 +/- 0.05 to 1.14 +/- 0.07 mmol/L, P less than .005) in the patients who received chromium. There was no change in serum cholesterol or blood glucose during the study. PMID- 1619997 TI - Intracellular free-magnesium levels in vascular smooth muscle and striated muscle cells of the spontaneously hypertensive rat. AB - In humans with essential hypertension and in spontaneously hypertensive rats (SHR), insulin resistance may be present even in lean individuals. As the basis for this abnormality is unknown, we have used a newly developed fluorophore to measure intracellular free-Mg2+ concentrations in cultured aortic vascular smooth muscle cells and striated muscle cells from SHR and normotensive Wistar Kyoto (WKY) rats. Intracellular free-Mg2+ levels were lower in both striated muscle cells (SHR, 0.423 +/- 0.077 mmol.L-1 v WKY, 0.559 +/- 0.068 mmol.L-1; P less than .001) and vascular smooth muscle cells (SHR, 0.406 +/- 0.067 mmol.L-1 v WKY, 0.625 +/- 0.077 mmol.L-1; P less than .001) from hypertensive animals. This widespread, intrinsic defect in the regulation of intracellular Mg2+ may explain the increased vascular resistance and reduced insulin sensitivity present in hypertension. PMID- 1619998 TI - Red blood cell uridine sugar nucleotide levels in patients with classic galactosemia and other metabolic disorders. AB - While dietary galactose restriction eliminates the life-threatening complications of classic galactosemia, central nervous system and ovarian disease are still evident in these patients, despite milk restriction. Because of the possibility that reduced tissue levels of uridine diphosphate galactose (UDPgalactose), the product of the deficient enzyme, galactose-1-phosphate uridyltransferase, are the cause of these unexplained complications, we have measured the concentration of red blood cell (RBC) uridine sugar nucleotides in these patients, comparing their values not only with those of normal subjects, but also with those of children who have other metabolic disorders. RBC UDPgalactose and uridine diphosphate glucose (UDPglucose) levels were measured by high-performance liquid chromatography (HPLC) in 35 control subjects, 24 galactosemic patients, and 19 patients with inborn errors of amino acid, organic acid, or ammonia metabolism. The last group of patients served as dietary controls, as they were all on special low-protein diets that restricted milk intake. The mean levels of UDPgalactose in galactosemic children and adults were 38% and 54% lower, respectively, than the levels in normal children and adults. While only six of 19 galactosemic children had levels below the 95% confidence limit for normals, four of five galactosemic adults had levels of UDPgalactose in the low range. The mean UDPgalactose level in children with other metabolic diseases who were on a low milk diet was also reduced by 38%, with a mean not significantly different from galactosemics. Compared with normal adults, the level of UDPglucose in galactosemic adults was also reduced by 29%, with three of five affected adults having UDPglucose values below the 95% confidence limit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1619999 TI - Effect of fatty acids on rat liver nuclear T3-receptor binding. AB - The effects of selected fatty acids (linoleic, oleic, and palmitic) on triiodothyronine (T3)-receptor binding were compared in isolated rat hepatocytes, rat liver nuclei, and receptor protein. Scatchard analysis indicated that the inhibition of T3-receptor binding by fatty acids was characterized by an increase in Kd and no change in maximum binding capacity (MBC). In isolated receptors, the rank order of potency for inhibition was linoleic acid greater than oleic acid greater than palmitic acid. The Ki for oleic acid in isolated receptors was the same as that for whole nuclei (15.4 +/- 1.3 v 16.3 +/- 1.9 mumol/L, respectively), indicating that the inhibition of nuclear T3 binding is probably at the level of the receptor protein itself. In isolated hepatocytes, linoleic acid was more potent than oleic acid in inhibiting T3 binding to nuclear receptors. Cell-associated T3 was not affected by the presence of fatty acids, implying that cellular uptake of T3 was not inhibited. High concentrations of fatty acids were necessary for inhibition of T3-receptor binding in isolated hepatocytes, with linoleic acid being one to two orders of magnitude less potent in isolated hepatocytes compared with isolated receptors (Ki, 179 +/- 12 v 4.4 +/ 0.5 mumol/L, respectively). It is concluded that the inhibitory effect of fatty acids on T3-receptor binding in isolated rat hepatocytes probably occurs at the level of the nuclear receptor, and does not involve an inhibition of the access of T3 to the receptor. However, in vivo it seems unlikely that fatty acids will have access to the nuclear receptors in sufficiently high concentrations to affect T3-receptor binding in liver cells. PMID- 1620000 TI - Detection and hormonal regulation of the mRNA for cytosolic phosphoenolpyruvate carboxykinase in rat lung. AB - We have studied the presence of the messenger RNA (mRNA) for the cytosolic enzyme, phosphoenolpyruvate carboxykinase (PEPCK), in rat lung by Northern blot hybridization to a complementary DNA (cDNA) probe. Lung from normal rats contained substantial amounts of this mRNA, although its relative concentration was approximately six times lower than in liver. Fasting produced an eightfold increase in the content of the enzyme mRNA in lung, which could be reverted to normal values by glucose refeeding. Induced diabetes also resulted in a sevenfold increase of the levels of PEPCK mRNA in lung. Dexamethasone, thyroid hormone, dibutyryl cyclic adenosine monophosphate (cAMP), histamine, and serotonin also induced important accumulations of the enzyme mRNA without affecting the concentration of beta-tubulin mRNA measured as reference. Thus, the PEPCK gene appears to be regulated in a similar manner in lung and liver. The results suggest that PEPCK may be involved in lung metabolism in starvation, diabetes, and other specific hormonal situations. PMID- 1620001 TI - AMA continues to work on RBRVS implementation. PMID- 1620002 TI - Affordable healthcare. The big issue. PMID- 1620003 TI - MSMS reimbursement roundup. PMID- 1620004 TI - BCBSM service to physicians improving, MSMS survey reveals. MSMS Committee still seeking more improvements. PMID- 1620005 TI - Accent and the international medical graduate. Education, not legislation, is the answer. PMID- 1620006 TI - Medicine in the UP. Part II. PMID- 1620007 TI - Rural health problems plague western UP. PMID- 1620008 TI - Your vote and the future of medicine. PMID- 1620009 TI - Bloodborne pathogens and right to know: a physician's guide to MIOSHA regulations. PMID- 1620010 TI - Glass ceiling. PMID- 1620011 TI - Fine needle aspiration biopsy of the thyroid. PMID- 1620012 TI - Immediate management of the burned patient. PMID- 1620013 TI - Transdermal oestrogen replacement therapy. PMID- 1620014 TI - Effectiveness, efficiency and the use and misuse of radiology. PMID- 1620015 TI - HIV risk behaviour among injecting drug users in Perth: the Australian National AIDS and Injecting Drug Use Study. AB - OBJECTIVE: This study was carried out in 1989 to examine behaviour involving risk of human immunodeficiency virus (HIV) infection and to measure the prevalence of HIV antibodies in a sample of injecting drug users (IDUs) in Perth. DESIGN: The study was a cross-sectional survey with a sample of convenience of 196 IDUs drawn from drug treatment (54%) and non-treatment (46%) populations. RESULTS: Sixty five per cent of the sample were men and 35% women. Subjects were predominantly heterosexual, were in their late twenties, had not completed secondary school, and were on sickness, unemployment or pension benefits. The majority were poly drug users, but heroin and amphetamines were the only drugs that had been injected by more than 20% of the sample more than once a month. Respondents reported injecting an average of 43.6 (SD 83.6) times a month and using 33.7 (SD 55.4) new needles a month. The majority (70%) had injected within weeks of the interview. Sixty-seven per cent had shared needles within months. Respondents claimed to pass on used needles more frequently than to accept them, and were most likely to share with close friends or lovers when clean needles were unavailable and/or when they were withdrawing. While most respondents cleaned used needles, few used bleach all or most of the time. Most (78%) respondents had been tested for HIV seropositivity at least once. Most had multiple sexual partners and 92.3% had engaged in at least one unsafe sexual practice during the previous six months. Sixty-four per cent had changed some aspect of drug using, and 38% some aspect of sexual behaviour since hearing about the acquired immunodeficiency syndrome (AIDS). HIV seroprevalence for the 179 respondents who were tested was 2.2%, but this figure should not be taken as an estimate of seroprevalence for the Perth IDU population. CONCLUSION: Respondents' behaviour placed them at a high level of risk for HIV infection. Based on reported behaviour, it is recommended that education for IDUs in Perth should emphasise, among other things: not passing on used needles; cleaning used needles and syringes with bleach; planning ahead so that sterile equipment is available; and further risk reduction, particularly the adoption of safer sexual practices. PMID- 1620017 TI - Medical records in general practice. PMID- 1620016 TI - Infection with Nocardia species in Queensland. A review of 102 clinical isolates. AB - OBJECTIVE: To review the species distribution, pathologic significance and disease associations of clinical isolates of Nocardia and related bacteria in Queensland, and to examine the characteristics, treatment and outcome of patients infected with these organisms. DESIGN AND SETTING: A retrospective review of Queensland State Health Laboratory records provided microbiological data for Nocardia isolates referred from other laboratories during the period January 1983 to December 1988. Clinical information was extracted from hospital case notes, or obtained from detailed questionnaires completed by attending physicians. Nocardia isolates were classified as "significant" if specific treatment for nocardiosis was given, or on the basis of autopsy findings. PATIENTS: One hundred and two patients had a Nocardia species or a related organism isolated from clinical specimens during the study period. RESULTS: The 102 isolates included Nocardia asteroides (45), N, brasiliensis (35), N. caviae (5) and N. transvalensis (5). Clinical results were available for 93 patients, of whom 74 (80%) had a significant isolate recovered. Primary pulmonary or disseminated disease occurred in 35 patients, and was caused mainly by N. asteroides. Significant infections of skin and soft tissues, primarily due to N. brasiliensis, were found in 39 patients. Preexisting lung disease and treatment with steroids and immunosuppression were risk factors for pulmonary and disseminated nocardiosis. A history of inoculation in an outdoor setting was frequent in patients with cutaneous disease. Antibiotic regimens that included trimethoprim sulfamethoxazole or another sulfonamide agent were used to treat the majority of patients with significant infection. Deaths were confined to those with pulmonary and disseminated disease, with a case fatality rate of 40% in that group. CONCLUSION: Infection with Nocardia species appears to be more common than is generally appreciated. The local species distribution and disease spectrum are similar to those described elsewhere. A high index of suspicion for nocardiosis should be maintained in susceptible hosts with pulmonary infiltrates, particularly when there is evidence for metastatic infection, and in patients with superficial infections and a history of outdoor injury. PMID- 1620018 TI - Assessment of medical students in general practice. AB - Assessment of medical students in general practice provides a unique challenge to medical educators as it has an extremely broad and varied curriculum. This paper discusses some of the main challenges and choices presented to educators and outlines and one model of assessment currently used at the University of Melbourne. Integration of a variety of assessment tools and a greater contribution to the final examination are important considerations for the future of general practice and assessment in Australian medical schools. PMID- 1620019 TI - Non-dilated urinary tract obstruction. AB - OBJECTIVE: To describe the occurrence of obstructive uropathy in the absence of dilatation of the urinary tract. CLINICAL FEATURES: Five cases of non-dilated obstructive nephropathy are described. All patients were uraemic on presentation. Obstruction was caused by retroperitoneal malignancy in two patients and uric acid lithiasis in the remaining three. All patients had at least one ultrasound examination. Isotope renography and computed tomography were performed in three and four patients respectively. None of these imaging techniques suggested obstruction in any of the cases. Radionuclide scans were characterised by unusually poor perfusion and parenchymal phase images. INTERVENTION AND OUTCOME: An immediate diuresis and a rapid return of normal renal function occurred after relief of the obstruction in all cases. CONCLUSION: The absence of dilatation in obstructive nephropathy is uncommon but may be responsible for delayed diagnosis and management of a readily treatable cause of acute renal failure. PMID- 1620020 TI - Drug-induced renal disease. AB - OBJECTIVE: To review drug-induced renal disease with emphasis on current issues and practical problems with commonly used agents. DATA SOURCES: English language literature search using MEDLINE, Index Medicus, textbook articles and relevant reviews. STUDY SELECTION: Drugs in common use were reviewed in detail. Uncommonly used drugs or those with only a few reports of nephrotoxicity were excluded from this review. DATA SYNTHESIS: The clinical patterns of nephrotoxicity include an episode of acute deterioration of renal function, chronic renal failure and proteinuria which may be severe enough to cause the nephrotic syndrome. Diagnosis is made by clinical suspicion, distinctive clinical patterns and usually improvement in renal function on drug withdrawal. CONCLUSION: A high index of suspicion is necessary to detect drug-induced renal disease particularly with increasing availability of over-the-counter drugs. Drugs should always be suspected of causing renal disease where no alternative cause is obvious. When any doubt exists the agent in question should be withdrawn. PMID- 1620021 TI - Why does Australia have no national drug policy? PMID- 1620022 TI - Trematode eggs in faeces of aboriginal and islander children. PMID- 1620023 TI - The cost of cervical screening by general practitioners. PMID- 1620024 TI - Emergency department experience of a Scout jamboree. PMID- 1620026 TI - Overseas medical practitioners and "racial discrimination". PMID- 1620025 TI - Myocardial lesions in SIDS. PMID- 1620027 TI - Malaria in Townsville. PMID- 1620028 TI - Non-prescription use of bronchodilator aerosols. PMID- 1620029 TI - Of spines, braces and steel rods. PMID- 1620030 TI - Analgesia for day surgery. PMID- 1620031 TI - Hormone replacement therapy and common sense. PMID- 1620032 TI - In search of the pathogenesis of refractory cervicobrachial pain syndrome. PMID- 1620033 TI - Blue-green algae (cyanobacteria) PMID- 1620034 TI - The occurrence of chickenpox. PMID- 1620036 TI - A review of electronic portal imaging devices (EPIDs). AB - On-line electronic portal imaging devices are beginning to come into clinical service in support of radiotherapy. A variety of technologies are being explored to provide real-time or near real-time images of patient anatomy within x-ray fields during treatment on linear accelerators. The availability of these devices makes it feasible to verify treatment portals with much greater frequency and clarity than with film. This article reviews the physics of high-energy imaging and describes the operation principles of the electronic portal imaging devices that are under development or are beginning to be used clinically. PMID- 1620035 TI - Treatment of candida epididymo-orchitis with oral fluconazole. PMID- 1620037 TI - The spatial and energy dependence of bremsstrahlung production about beta point sources in H2O. AB - A Monte Carlo simulation was performed to characterize the spatial and energy distribution of bremsstrahlung radiation from beta point sources important to radioimmunotherapy (RIT). Using the EGS4 Monte Carlo code, the isotropic emission and transport of monoenergetic 0.1-, 0.5-, 1.0-, 2.0-, and 3.0-MeV electrons and 32P and 90Y beta particles was simulated in an infinite, homogeneous H2O phantom. The probability of bremsstrahlung production for each Monte Carlo-simulated electron step was accumulated in energy intervals not exceeding 5 keV and stored as a function of radial position. To validate this scheme, the EGS4 code was tested in the continuous slowing down approximation (csda) mode, with resulting radiation yields seen to agree with values in ICRU Report No. 37 (ICRU, Bethesda, MD, 1984) to better than 1.6%. The radiation yield calculated with the simulation of secondary particles is seen to be 3%-5% greater than the csda yield. The photon energy distributions are characterized by a typically broad bremsstrahlung spectrum with the probability of photon generation decreasing with radial distance. In the energy range 0.05-0.511 MeV, the probability for bremsstrahlung production from 90Y (2.76 x 10(-2) decay-1) is twice that from 32P (1.35 x 10(-2) decay-1). When passed through 10 cm of H2O and put upon a standard NaI scintillation camera, count rates of 2.3 x 10(-6) and 1.2 x 10(-6) counts s-1 Bq 1 are estimated from point sources of 90Y and 32P. These results predict the inherent spatial resolution limitation and provide the initial data required for modeling and analyzing the scatter, attenuation, and image formation processes in quantitative imaging of bremsstrahlung for RIT dosimetry. PMID- 1620038 TI - Electron bolus design for radiotherapy treatment planning: bolus design algorithms. AB - Computer algorithms to design bolus for electron beam radiotherapy treatment planning were investigated. Because of the significant electron multiple scatter, there is no unique solution to the problem of bolus design. However, using a sequence of operators, a bolus can be designed that attempts to meet three important criteria: adequate dose delivery to the target volume, avoidance of critical structures, and dose homogeneity within the target volume. Initial calculation of bolus shape was based upon creation operators forcing either the physical or the effective depths of the distal surface of the target volume to a specified value. Modification operators were then applied to the bolus to alter the shape to better meet the design criteria. Because the operators each address a single dosimetric issue, they can often adversely affect some other attribute of the dose distribution. In addition, an extension operator is used to design the bolus thickness outside the target volume. Application of these operators is therefore carried out in certain sequences and each may be used more than once in the design of a particular bolus. The effects of these operators on both the bolus and the resulting dose distribution are investigated for test geometries and patient geometries in the nose, parotid, and paraspinal region. PMID- 1620039 TI - Optimal electron-beam treatment planning for retinoblastoma using a new three dimensional Monte Carlo-based treatment planning system. AB - Electron-beam treatment planning for retinoblastoma was investigated and an optimal treatment plan was devised for a particular case using a new three dimensional Monte Carlo-based treatment planning system known to be capable of correctly predicting dose perturbations caused by body surface obliquities and tissue heterogeneities. Computed tomography (CT) data files were used to construct a three-dimensional eye phantom representing the anatomy of a child's orbit. Dose distributions in sagittal, transverse, and coronal planes were predicted with 1-mm resolution. Study of these distributions led to an optimal treatment plan consisting of an anterior-lateral pair, with the anterior field being a 10-MeV, 30-mm-diam circular field, centrally blocked by a 10-mm-diam lucite lens shield and the lateral field being a 16-MeV, 30 x 25-mm D-shaped field. The anterior field delivers a therapeutic dose to the ora serrata, but it underdoses the posterior retinal surface behind the lens shield; the lateral field provides the necessary boost dose to the posterior retinal surface. An equally weighted combination of the two fields produces a dose distribution in which the entire retinal surface receives a therapeutic dose, with less than 10% of that dose being delivered to the lens, brain, and the contralateral orbit. PMID- 1620040 TI - Some considerations regarding w values for heavy charged-particle radiotherapy. PMID- 1620042 TI - Generation and use of measurement-based 3-D dose distributions for 3-D dose calculation verification. AB - A 3-D radiation therapy treatment planning system calculates dose to an entire volume of points and therefore requires a 3-D distribution of measured dose values for quality assurance and dose calculation verification. To measure such a volumetric distribution with a scanning ion chamber is prohibitively time consuming. A method is presented for the generation of a 3-D grid of dose values based on beam's-eye-view (BEV) film dosimetry. For each field configuration of interest, a set of BEV films at different depths is obtained and digitized, and the optical densities are converted to dose. To reduce inaccuracies associated with film measurement of megavoltage photon depth doses, doses on the different planes are normalized using an ion-chamber measurement of the depth dose. A 3-D grid of dose values is created by interpolation between BEV planes along divergent beam rays. This matrix of measurement-based dose values can then be compared to calculations over the entire volume of interest. This method is demonstrated for three different field configurations. Accuracy of the film measured dose values is determined by 1-D and 2-D comparisons with ion chamber measurements. Film and ion chamber measurements agree within 2% in the central field regions and within 2.0 mm in the penumbral regions. PMID- 1620041 TI - An interactive beam-weight optimization tool for three-dimensional radiotherapy treatment planning. AB - A computer software tool has been developed to aid the treatment planner in selecting beam weights for three-dimensional radiotherapy treatment planning. The program consists of a feasibility search algorithm embedded in an interactive, user-friendly driving program. The feasibility search algorithm is based on the iterative relaxation algorithm of Cimmino [La Ricerca Scientifica, Vol. I, pp. 326-333 (1938)] as applied to the radiotherapy inverse problem by Altschuler et al. [Med. Phys. 13, 590 (1986)]. Relative importances of structures based upon clinical considerations can be incorporated into the algorithm. In order to speed convergence, the relaxation parameter is made to vary, with its value based upon a measure of deviation from feasibility. The interactive driving program is designed so that the treatment planner can make reasonable judgments regarding the acceptability of a plan in the event that the dose constraints yield no feasible solution. An example of the use of this program applied to a problem in three-dimensional radiotherapy treatment planning is illustrated. PMID- 1620043 TI - Investigation of the nonlinear aspects of imaging through a highly scattering medium. AB - The edge-spread function that is expected when imaging a sharp edge in a highly scattering medium using a time-of-flight imaging system has been investigated. Experimental results have been compared with computer simulations. The effect of scattering is to broaden the image of the edge, accompanied by an offset of the midpoint (50% transmission) of the edge. Small random errors in the measurement of the time of flight results in an increase in the offset of the edge position at very short times of flight. The offset in the midpoint of the edge is evidence of the nonlinear nature imaging process, in view of which we conclude that nonlinear algorithms will be necessary to maximize the image information available from measured intensities. PMID- 1620044 TI - Coordinate transformation as a primary representation of radiotherapy beam geometry. AB - An approach to both geometric specification of radiotherapy beams and computerized solution of geometric treatment planning problems using coordinate transformations is presented. It is demonstrated that the specification of the geometric relationship of a treatment beam to a patient can be uniquely given by a 4 x 4 coordinate transformation matrix, and that the matrix representation can be translated from (and to) the more conventional machine-based specification of geometry. This approach enables a compact representation of the patient/beam geometry which is independent of the specific labeling conventions of the treatment machine and which can be directly exploited in the solution of treatment planning problems. Beam geometry can be easily described either in terms of the natural degrees of freedom of a therapy machine or in terms of alternative, problem-specific frames of reference. The ability to use these various frames of reference interchangeably allows the designer of treatment design software to present appropriate task-specific user interfaces for arbitrarily complex tasks, and thus reduce the cognitive burden on users of the software. PMID- 1620045 TI - Stereotactic radiosurgery: dose-volume analysis of linear accelerator techniques. AB - Stereotactic radiosurgery of the brain may be accomplished with a linear accelerator by performing several noncoplanar arcs of a highly collimated beam focused at a point. The shape of the radiation distribution produced by this technique is affected by the beam energy, field size, and the number and size of the arcs. The influence of these parameters on the resulting radiation distributions was analyzed by computing dose volume histograms for a typical brain. Dose volume functions were computed for: (a) the energy range of 4-24 MV x rays; (b) target sizes of 1-4 cm; and (c) 1-11 arcs and dynamic rotation. The dose volume histograms were found to be dependent on the number of arcs for target sizes of 1-4 cm. However, these differences were minimal for techniques with 4 arcs or more. The influence of beam energy on the dose volume histogram was also found to be minimal. PMID- 1620046 TI - Dosimetric characteristics of wedges mounted beyond the blocking tray. AB - In a beam accessory configuration for a linear accelerator using a prototype multileaf collimator, newly designed wedges were mounted beyond the blocking tray. The isodose curves, depth of maximum dose, surface dose, and wedge transmission factors were measured for the wedges designed for this unique configuration. The same set of wedges was used for both 6- and 18-MV x rays. The shape of the wedged isodose curves was essentially unchanged from those produced by the conventional wedges located above the blocking tray. The isodose curves exhibited the desired wedge angles over the range of field sizes from 5 x 5 to 15 x 40 cm. In the 10 x 10-cm field, the average difference between the observed wedge angle and the desired wedge angle was 3.8 degrees. The surface doses ranged from 18% to 35% for the wedged 10 x 10-cm fields as compared with about 15% for the same open field. Dosimetrically the wedges were acceptable for clinical use. PMID- 1620047 TI - High-energy x-ray beam calibrations using scaling. AB - When calibrating high-energy x-ray beams, it is convenient to measure in a plastic phantom and convert the result to absorbed dose in water at a specified depth, field size, and distance from the source. By combining the scaling theorem with the observation that TAR is independent of the distance to the source, it is demonstrated that the measurement in plastic can be made at the same source detector distance but scaling depth and field size. Experiments to support this were made in acrylic and water with 6- and 25-MV x rays and at different distances from the source. The agreement between the calibrations in acrylic and water was comparable to that using the current national protocol, which recommends the scaling of depth only while using the same field size and source detector distance in the two media and correcting for the difference in scatter dose. It was confirmed that the scaling factor may be the ratio between the electron densities of acrylic and water, or the ratio between the linear attenuation coefficients. A method to determine this factor directly is also described. PMID- 1620048 TI - Radial dose distribution from 192Ir seeds at distances far from the source. AB - Most current tissue attenuation and scattering factors for 192Ir are valid only to distances of 15 cm or less. Monte Carlo calculations using the EGS4 computer code were used to calculate tissue attenuation and scattering factors for 192Ir seed sources with both stainless steel encapsulation and with Pt encapsulation out to a distance of 32 cm from the sources. The data clearly show that polynomial tissue attenuation and scattering factors cannot be extrapolated beyond their range. Encapsulation specific factors are presented here that are valid at large distances from the source. PMID- 1620049 TI - Long-term use of an isotope check source for verification of ion chamber calibration. AB - A radioactive check source is recommended for operational and constancy checks of dosimetry systems used for the calibration of therapeutic x-ray generators, including linear accelerators. Eight years of data have been analyzed for two ion chambers (and their associated electrometers) irradiated at fixed geometry in such a device. These dosimetry systems have also been calibrated every 2 years at a single Accredited Dosimetry Calibration Laboratory. Our analysis suggests that when a check source is used, and the results are consistent, the interval between formal calibrations can be lengthened. PMID- 1620050 TI - A chamber and electrometer calibration factor as determined by each of the five AAPM accredited dosimetry calibration laboratories. AB - The same calibration grade ionization chamber and electrometer were sequentially sent to all five currently AAPM Accredited Dosimetry Calibration Laboratories (ADCL). A Cesium-137 based check device was utilized to ensure chamber and electrometer factor constancy and showed a maximum deviation of 0.32% (typically less than 0.1%) over the 227 days needed to complete the intercomparison. The chamber and electrometer calibration factor provided by each of the five ADCLs were analyzed for consistency. The maximum percent difference in reported chamber factor between all five ADCLs was 1.40%. The reported electrometer factor had a maximum discrepancy of only 0.50%. System (chamber plus electrometer) factors as provided by three of the five ADCLs had a maximum discrepancy of 1.51%. PMID- 1620051 TI - Chamber replacement correction in absorbed dose calibrations. PMID- 1620052 TI - Comparison of IAEA 1987 and AAPM 1983 protocols for dosimetry calibration of radiotherapy beams. PMID- 1620053 TI - Acceptance testing of magnetic resonance imaging systems: report of AAPM Nuclear Magnetic Resonance Task Group No. 6. PMID- 1620054 TI - Recommendations on performance characteristics of diagnostic exposure meters: report of AAPM Diagnostic X-Ray Imaging Task Group No. 6. AB - Task Group 6 of the Diagnostic X-Ray Imaging Committee of the American Association of Physicists in Medicine (AAPM) was appointed to develop performance standards for diagnostic x-ray exposure meters. The recommendations as approved by the Diagnostic X-Ray Imaging Committee and the Science Council of the AAPM are delineated in this report and provide specifications on meter precision, calibration accuracy, calibration reference points, linearity, energy dependence, exposure rate dependence, leakage, amplification gain settings, directional dependence, the stem effect, constancy checks, and calibration intervals. The report summarizes recommendations for meters used in mammography, general purpose radiography including special procedures, computed tomography, and radiation safety surveys for x-ray radiography. PMID- 1620055 TI - Systematic bias in basis material decomposition applied to quantitative dual energy x-ray imaging. AB - Basis material decomposition represents dual-energy x-ray attenuation measurements in terms of the attenuation coefficients or thickness of two standard materials which, when combined, produce attenuation equivalent to the object being measured. In tomographic imaging, the reconstructed attenuation coefficient is calculated in terms of the attenuation coefficients of the basis materials, while in projection imaging, the thicknesses of two materials can be specified in terms of the basis materials. This analysis shows that basis material decomposition is exact in a dual-monoenergetic system, but for broad spectra, x-ray beam hardening introduces a bias into quantitative measurements. The error is small enough that it can be ignored when dual-energy imaging is used primarily to enhance the contrast of one material over another. The magnitude of the error in quantitative measurements depends on the details of the specific application including the energy of the x-ray beam, and the composition and thickness of the materials included in the object. The magnitude of the error for dual-energy bone densitometry has been analyzed using a first-order propagation of error analysis and the calculations verified by computer simulation. This analysis shows that the magnitude of the systematic error can be as high as 3% for 1 g/cm2 of bone mineral when aluminum and acrylic basis materials are used for the calibration. This systematic error is eliminated when the basis materials are the same as the materials that are being quantified (i.e., bone mineral and water). PMID- 1620056 TI - Evaluation of a new set of calibration standards for the measurement of fat content via DPA and DXA. AB - A simulation study was performed to evaluate a new set of calibration standards for estimating the fat content of the body via dual-photon absorptiometry (DPA) and dual-energy x-ray absorptiometry (DXA). The standards, proposed by Nord and Payne [presented at the 2nd meeting of The Bath Conference on Bone Mineral Measurement (1990)] consist of stearic acid (100% fat) and 0.6% NaCl in water (100% lean). They were compared with other standards consisting of average composition adipose/muscle tissues and fatty adipose/lean muscle tissues. Source and detector properties of a Gd-153 DPA system and three commercial DXA systems were modeled. For each system and calibration set, rms errors in the calculated fat contents of simulated tissues having fat mass percentages that ranged from about 4%-44% and thicknesses that ranged from 5-20 cm were determined. Beam hardening errors for the systems were evaluated as was a calibration technique employed by one of the manufacturers to correct for such errors. In general, the smallest rms errors (2% or less when the calibration standards and tissues were of equal thickness) were obtained with the average adipose/muscle standards. Equivalent results were obtained with standards consisting of stearic acid and 0.8% NaCl. The latter is a higher salt content than proposed by Nord and Payne and results from differences in the x-ray attenuation coefficients that were employed in calculating the fat equivalence of water. Other, more convenient standards, such as lucite and water may be employed by using appropriate fat equivalences (approximately 69% for lucite and approximately 10% for water). Beam hardening errors for the DXA systems are considerable, and the simulated correction technique was shown to be effective. PMID- 1620057 TI - Fluoroscopic performance tests using a portable computer/frame grabber: Wiener spectra measurements. AB - Currently, routine tests of fluoroscopic image quality in common use are highly subjective. As part of an effort to develop more quantitative routine tests of fluoroscopic image quality, a method was developed to quickly and easily measure Wiener spectra (WS) of TV-viewed fluoroscopic systems that considers both spatial and temporal noise correlations. A PC-mounted frame grabber captures images at the TV frame rate to form a three-dimensional (3-D) array of pixels. Scans of a "two-dimensional slit" are then synthesized from which a one-dimensional central section of a 3-D WS is calculated. To avoid errors due to coarse (8-bit) quantization, a video amplifier is used to expand a portion of the signal to the full digitizer range. A reference signal (2 mm of aluminum) is then used to normalize image contrast. Ensemble averages of 250 spectra were obtained in approximately 1 min, including all processing. Results are presented to demonstrate reproducibility, sensitivity, and behavior of the WS. The eventual goal of this work is to use this method in conjunction with measurements of an MTF to calculate fundamental descriptors of image quality, such as SNR and NEQ. PMID- 1620058 TI - Describing the signal-transfer characteristics of asymmetrical radiographic screen-film systems. AB - The measurement of modulation transfer function for radiographic screen-film systems depends critically upon a proper linearization of the measured line spread function. This is normally done by photographic photometry (i.e., using the measured density versus log exposure relationship to transform the density line spread function into an exposure line spread function). It has been long appreciated that this procedure may fail for asymmetrical dual screen systems that use film with emulsion coated on both sides of the support. The advent of asymmetrical and near-zero crossover films that can be used with highly asymmetric screen pairs has prompted a reinvestigation of these concerns about the definition and measurement of modulation transfer function. For such cases, it is useful to define the contrast transfer function, which is a function of exposure and spatial frequency. When normalized by its zero frequency value the contrast transfer function can serve as the "effective MTF" for low-contrast input signals in such systems. In the limit of symmetrical systems this quantity approaches the conventionally measured MTF. The utility of this approach is demonstrated by applying it to a commercially available asymmetrical screen-film combination. PMID- 1620059 TI - Density related errors encountered with an electrostatically coupled film digitizer tablet. PMID- 1620060 TI - Broad line quantitative chemical shift spectroscopy. AB - Proton NMR spectroscopy was applied to quantitate the measurement of total body water/fat distributions in vivo. A special MR protocol was developed to excite a thick slab of tissue and display the magnitude NMR spectrum of the collected response signal. Very short echo time TE (8 ms) and long repetition time TR (4000 ms) were used to minimize relaxation damping of the signal intensities. The spectrum was then decomposed into individual lines and proton densities of different species were calculated. Proton density information was converted into weight percentage data using stoichiometrical and physiological information. The technique was validated using phantoms that contained different mixtures of water/maize oil. A high-resolution NMR spectrum of maize oil samples was used to determine the stoichiometric information. The test results showed good agreement with the known composition of the phantom within the whole range of water content (0-100%). This method is very fast since no phase encoding of data is required. Preliminary results for monkeys show promising potential in clinical applications. PMID- 1620061 TI - Automated lesion detection and lesion quantitation in MR images using autoassociative memory. AB - Previous efforts concerning lesion extraction in radiologic images indicated that autoassociative memory models can be a valuable tool in automated lesion detection. Preliminary results are expanded to resolve the technical problems of image registration and magnification. Instead of operating on selected portions of the MR images, each entire image matrix is operated upon as image vector comprising all stacked columns of the matrix. Spin density weighted images (TR = 3000 ms and TE = 40 ms) of 42 normal subjects were remapped and standardized with respect to location and magnification. All image vectors were orthonormalized to span a linear manifold. Standardized abnormal image vectors were then tested by the stored autoassociative memory and the abnormalities (novelties) were extracted by application of an autocorrelation matrix to the input vector. The autocorrelation matrix is computed using image vectors from normal subjects. The lesions (multiple sclerosis and tumors) are then identified as the orthogonal component to the linear manifold spanned by the basis vectors of the normal brain scans. Lesion extraction has been achieved with the intention of quantitating and staging diseased parenchyma after automated edge detection. PMID- 1620062 TI - Quantitative phase-velocity MR imaging of in-plane laminar flow: effect of fluid velocity, vessel diameter, and slice thickness. AB - Quantitative MR phase imaging is frequently used to measure spin velocities. A potential difficulty may arise, however, when in-plane phase images are acquired of a vessel carrying laminar flow, for which the fluid velocity profile is parabolic. In that case, depending on the flow velocity (v), the vessel diameter (D), and the chosen MR slice thickness (ST), a spin velocity gradient will be present to some extent within each intraluminal voxel. The resulting intravoxel phase dispersion may be expected to affect the net pixel phase value, and hence compromise the assumed linear correlation between phase shift and velocity. In this study, the effects of alterations of v, D, and ST on the apparent image phase are investigated for the case of laminar flow directed parallel to the sequence read gradient. A theoretical model is developed and the conclusions experimentally tested using a flow phantom. The data demonstrate that when quantitating inplane phase-flow images, significant velocity underestimations may occur when the net flow-induced phase shifts are small and the MR slice thickness is an appreciable fraction of the vessel diameter. PMID- 1620063 TI - Nuclear magnetic relaxation characterization of irradiated Fricke solution. AB - The spin-lattice relaxation rate R1(= T1(-1) of irradiated Fricke solution was studied as a function of the absorbed dose D. The R1 increases linearly with dose up to D approximately 400 Gy after which the response saturates. A model describing the R1 of a solution of either ferrous (Fe2+) or ferric (Fe3+) ions is presented; it is based on the spin relaxation of protons on water molecules in the bulk and protons on water molecules in the coordination shells of the ions with fast exchange occurring between the two water environments. All inherent relaxation parameters of the different proton groups are determined empirically at NMR frequencies of 9 and 25 MHz. An extension of the model is made to describe the spin-lattice relaxation behavior of irradiated Fricke solution. Good agreement between model predictions and experimental results is observed. The model relates the spin-lattice relaxation rate of a Fricke dosimeter to the chemical yield of ferric ion, thus potentially creating an absolute NMR dosimetry technique. Various practical aspects of the NMR-Fricke system, such as the optimal initial ferrous concentration and the NMR frequency dependence of the sensitivity, are described. PMID- 1620064 TI - Localized beta dosimetry of 131I-labeled antibodies in follicular lymphoma. AB - The purpose of this study is to assess the multicellular dosimetry of 131I labeled antibody in follicular lymphoma based on histological measurements on human tumor biopsy tissue. Photomicrographs of lymph node specimens were analyzed by first-order treatment to determine the mean values and statistical variations of the radii of follicles (260 +/- 90 microns), interfollicular distances (740 +/ 160 microns), and the number density of follicles [60 +/- 18 in a volume of (2 X 1480 microns)3]. Based on these measurements, two geometrical models were developed for localized beta dosimetry. The first, a regular cubic lattice model, assumes no variation in follicular radius of follicles and interfollicular distance. The second, a randomized distribution model, is a more complicated but more realistic representation of observed histological specimens. In this model, Monte Carlo methods were used to reconstruct the spatial distribution of follicles by simulating the distribution of the radii of follicles, interfollicular distances, and the number density of follicles. Dose calculations were performed using Berger's point kernels for absorbed-dose distribution for beta particles in water, assuming the 131I-labeled antibodies as point sources. It was assumed that the activity concentration of the labeled antibody within the follicles was ten times the activity concentration in the interfollicular spaces. The spatial distribution of localized dose was calculated for a tumor having an average dose of 40 Gy. The localized dose was found to be highly nonuniform, ranging from 20 to 90 Gy, and varying by a factor of about 2 from the average tumor dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620065 TI - Satellite RNAs of plant viruses: structures and biological effects. AB - Plant viruses often contain parasites of their own, referred to as satellites. Satellite RNAs are dependent on their associated (helper) virus for both replication and encapsidation. Satellite RNAs vary from 194 to approximately 1,500 nucleotides (nt). The larger satellites (900 to 1,500 nt) contain open reading frames and express proteins in vitro and in vivo, whereas the smaller satellites (194 to 700 nt) do not appear to produce functional proteins. The smaller satellites contain a high degree of secondary structure involving 49 to 73% of their sequences, with the circular satellites containing more base pairing than the linear satellites. Many of the smaller satellites produce multimeric forms during replication. There are various models to account for their formation and role in satellite replication. Some of these smaller satellites encode ribozymes and are able to undergo autocatalytic cleavage. The enzymology of satellite replication is poorly understood, as is the replication of their helper viruses. In many cases the coreplication of satellites suppresses the replication of the helper virus genome. This is usually paralleled by a reduction in the disease induced by the helper virus; however, there are notable exceptions in which the satellite exacerbates the pathogenicity of the helper virus, albeit on only a limited number of hosts. The ameliorative satellites are being assessed as biocontrol agents of virus-induced disease. In greenhouse studies, satellites have been known to "spontaneously" appear in virus cultures. The possible origin of satellites will be briefly considered. PMID- 1620066 TI - Sequestered end products and enzyme regulation: the case of ornithine decarboxylase. AB - The polyamines (putrescine, spermidine, and spermine) are synthesized by almost all organisms and are universally required for normal growth. Ornithine decarboxylase (ODC), an initial enzyme of polyamine synthesis, is one of the most highly regulated enzymes of eucaryotic organisms. Unusual mechanisms have evolved to control ODC, including rapid, polyamine-mediated turnover of the enzyme and control of the synthetic rate of the protein without change of its mRNA level. The high amplitude of regulation and the rapid variation in the level of the protein led biochemists to infer that polyamines had special cellular roles and that cells maintained polyamine concentrations within narrow limits. This view was sustained in part because of our continuing uncertainty about the actual biochemical roles of polyamines. In this article, we challenge the view that ODC regulation is related to precise adjustment of polyamine levels. In no organism does ODC display allosteric feedback inhibition, and in three types of organism, bacteria, fungi, and mammals, the size of polyamine pools may vary radically without having a profound effect on growth. We suggest that the apparent stability of polyamine pools in unstressed cells is due to their being largely bound to cellular polyanions. We further speculate that allosteric feedback inhibition, if it existed, would be inappropriately responsive to changes in the small, freely diffusible polyamine pool. Instead, mechanisms that control the amount of the ODC protein have appeared in most organisms, and even these are triggered inappropriately by variation of the binding of polyamines to ionic binding sites. In fact, feedback inhibition of ODC might be maladaptive during hypoosmotic stress or at the onset of growth, when organisms appear to require rapid increases in the size of their cellular polyamine pools. PMID- 1620068 TI - Establishment and expression of cellular polarity in fucoid zygotes. AB - Zygotes of fucoid algae have long been studied as a paradigm for cell polarity. Polarity is established early in the first cell cycle and is then expressed as localized growth and invariant cell division. The fertilized egg is a spherical cell and, by all accounts, bears little or no asymmetry. Polarity is acquired epigenetically a few hours later in the form of a rhizoid/thallus axis. The initial stage of polarization is axis selection, during which zygotes monitor environment gradients to determine the appropriate direction for rhizoid formation. In their natural setting in the intertidal zone, sunlight is probably the most important polarizing vector; rhizoids form away from the light. The mechanism by which zygotes perceive environmental gradients and transduce that information into an intracellular signal is unknown but may involve a phosphatidylinositol cycle. Once positional information has been recorded, the cytoplasm and membrane are reorganized in accordance with the vectorial information. The earliest detectable asymmetries in the polarizing zygote are localized secretion and generation of a transcellular electric current. Vesicle secretion and the inward limb of the current are localized at the presumptive rhizoid. The transcellular current may establish a cytoplasmic Ca2+ gradient constituting a morphogenetic field, but this remains controversial. Localized secretion and establishment of transcellular current are sensitive to treatment with cytochalasins, indicating that cytoplasmic reorganization is dependent on the actin cytoskeleton. The nascent axis at first is labile and susceptible to reorientation by subsequent environmental vectors but soon becomes irreversibly fixed in its orientation. Locking the axis in place requires both cell wall and F actin and is postulated to involve an indirect transmembrane bridge linking cortical actin to cell wall. This bridge anchors relevant structures at the presumptive rhizoid and thereby stabilizes the axis. Approximately halfway through the first cell cycle, the latent polarity is expressed morphologically in the form of rhizoid growth. Elongation is by tip growth and does not appear to be fundamentally different from tip growth in other organisms. The zygote always divides perpendicular to the growth axis, and this is controlled by the microtubule cytoskeleton. Two microtubule-organizing centers on the nuclear envelope rotate such that they align with the growth axis. They then serve as spindle poles during mitosis. Cytokinesis bisects the axial spindle, resulting in a transverse crosswall. Although the chronology of cellular events associated with polarity is by now rather detailed, causal mechanisms remain obscure. PMID- 1620070 TI - [Immunologic changes in diabetic ketoacidosis]. AB - We studied 13 children and adolescents during diabetic ketoacidosis; the duration of diabetes ranged from 1.4 to 6.0 years. A group of 13 diabetic sex, age and duration of disease-matched children served as control. Patients in ketoacidosis showed important abnormalities of T subset percentages (OKT3: 63.4 +/- 1.87% vs 72.1 +/- 3.4; p less than 0.001. OKT4: 37.18 +/- 1.85% vs 44.6 +/- 3.9; p less than 0.01. OKT8: 28.5 +/- 6.51% vs 28.1 +/- 1.9; p less than 0.04) and impaired neutrophil chemotaxis (53.10 +/- 3.3 vs 88.1 +/- 7.2; p less than 0.001). The patients showed normal levels of all classes of immunoglobulins. No correlation was observed between these abnormalities and the degree of ketoacidosis or glycaemia. When the patients were re-evaluated out of ketoacidosis, the values of the immunological parameters were normal and similar to those of the control group. PMID- 1620071 TI - [24-hour esophageal pH-metry in the evaluation of gastroesophageal reflux pathology]. AB - Gastro-esophageal reflux (GER) in infants was studied using 24-hour esophageal pH monitoring. Gastro-esophageal reflux was detected in 32/41 subjects. In our patients the main symptoms were vomiting, regurgitation, failure-to-thrive, chronic respiratory problems such as asthma, apnea, recurrent pneumonia. All patients with GER were treated appropriately with prone positioning and medical therapy (prokinetic agent and, eventually, ranitidine). Successful treatment of the reflux was obtained in all patients. In our opinion the 24-hour intraesophageal pH monitoring is a highly diagnostic test to identify the presence of GER and evaluate its gravity. PMID- 1620072 TI - [Acute nonbacterial bronchopneumopathies in the 1st years of life. Diagnostic strategies and clinico-epidemiological peculiarities]. AB - The authors summarise diagnostic strategies an clinical epidemiologic peculiarities of non-bacterial bronchopneumopathies in children. The role of classic viral agents (virus influenzal A-B, virus parainfluenza 2-3, RVS) is stressed without neglecting the role of other etiologic agents such as Chlamydia trachomatis, Mycoplasma pneumoniae and Pneumocystis carinii. The Authors point out the necessity of direct investigation (viral cultures, direct investigation in IF and ELISA, investigation with DNA probe use, etc.) and indirect serologic investigation to obtain the greatest possible accuracy an early diagnosis. PMID- 1620069 TI - Oxygen relations of nitrogen fixation in cyanobacteria. AB - The enigmatic coexistence of O2-sensitive nitrogenase and O2-evolving photosynthesis in diazotrophic cyanobacteria has fascinated researchers for over two decades. Research efforts in the past 10 years have revealed a range of O2 sensitivity of nitrogenase in different strains of cyanobacteria and a variety of adaptations for the protection of nitrogenase from damage by both atmospheric and photosynthetic sources of O2. The most complex and apparently most efficient mechanisms for the protection of nitrogenase are incorporated in the heterocysts, the N2-fixing cells of cyanobacteria. Genetic studies indicate that the controls of heterocyst development and nitrogenase synthesis are closely interrelated and that the expression of N2 fixation (nif) genes is regulated by pO2. PMID- 1620067 TI - Mechanism and regulation of eukaryotic protein synthesis. AB - This review presents a description of the numerous eukaryotic protein synthesis factors and their apparent sequential utilization in the processes of initiation, elongation, and termination. Additionally, the rare use of reinitiation and internal initiation is discussed, although little is known biochemically about these processes. Subsequently, control of translation is addressed in two different settings. The first is the global control of translation, which is effected by protein phosphorylation. The second is a series of specific mRNAs for which there is a direct and unique regulation of the synthesis of the gene product under study. Other examples of translational control are cited but not discussed, because the general mechanism for the regulation is unknown. Finally, as is often seen in an active area of investigation, there are several observations that cannot be readily accommodated by the general model presented in the first part of the review. Alternate explanations and various lines of experimentation are proposed to resolve these apparent contradictions. PMID- 1620073 TI - [Growth hormone secretion in response to the administration of thyrotropin releasing hormone (TRH) in children with insulin-dependent diabetes mellitus]. AB - In this study the Authors examined the response in growth hormone (GH) to thyrotrophin releasing hormone (TRH) administration in a group composed of 29 children (17 males, 12 females) suffering from insulin-dependent diabetes mellitus (IDDM) (group 1). All subjects were prepubertal, had a chronological age of 8.82 +/- 1.76 years (m +/- SD), a bone age of 8.60 +/- 1.65 years; the time elapsed since the diagnosis was 2.45 +/- 1.51 years, glycosylated hemoglobin (HbA1c) was 7.33 +/- 1.80%. Some of the same subjects (all those with a response in GH to TRH higher than 4 ng/ml; no. 11; group 2) were examined again 12-18 months later; as controls, 13 short children were also examined (group 3). All the subjects of the three groups showed a TSH peak ranging from 10-25 microU/ml, whereas GH peak resulted higher than 4 ng/ml ("paradoxical" response) in 6 subject of the group 1 and in an only subjects of the group 2. All the responders of the 3 groups showed a value in HbA1c higher than 8%. A significant difference was not present between males and females in GH and TSH values. Cortisol levels and glycaemia remained almost constant during the performance of the tests. By considering all the groups, TSH and GH values during TRH-test were not correlated with glycaemia, chronological age, bone age, the time elapsed since the diagnosis, height, height velocity, HbA1c values. In conclusion, our data demonstrated that "paradoxical" response in GH to TRH administration was present only in some subjects and particularly in those with a poor metabolic control of the disease. PMID- 1620074 TI - [Clinical implications of sensitization to inhalants in atopic dermatitis]. AB - In 104 children with atopic dermatitis (AD) and RAST tests for 2 inhalant and 9 food allergen mixtures, RAST results, severity of skin involvement and presence of respiratory symptoms by history were analyzed in addition to total serum IgE values available in 66 children. Overall frequency of sensibilization was high (74%) with more positive RAST results for foods than inhalants, although of the latter the only two tested were among the more frequently positive. When the subjects positive for inhalants were considered alone, the frequency of respiratory symptoms was significantly higher in those sensitized to both inhalant mixtures tested (dermatophagoides and graminaceae) and the presence of more severe skin lesions was more common among those sensitized to graminaceae. PMID- 1620075 TI - [Ehlers-Danlos syndrome. Description of 2 clinical cases]. AB - The paper describes the clinical symptoms and biochemical tests carried out in two girls suffering from Ehlers-Danlos syndrome. The most typical clinical feature, which is common to both cases, was the presence of skin alterations at the extensor surface level of elbows and, above all, knees. These alterations appeared to be delimited areas with irregular margins where the skin was thin, dry, hyperpigmented, wrinkled, with scanty or absent subcutaneous tissue. Biochemical tests carried out on cutaneous fibroblast cultures excluded the presence type I collagen alterations and an altered secretion of type I or III procollagen secretion. The Authors discuss the attribution of cases presented within the context of the various forms of Ehlers-Danlos syndrome in relation to clinical findings and the results of the biochemical tests. PMID- 1620077 TI - [AIDS in the world]. PMID- 1620076 TI - [Use of intravenous immunoglobulins in Guillain-Barre syndrome]. AB - The aim of the study was to assess the utility of intravenous integral molecule immunoglobulin treatment in Guillain-Barre syndrome. The etiopathogenesis of this syndrome is still unclear but it seems increasingly likely that immune phenomena are involved in the genesis of the neurological lesions. This would explain the efficacy of iv immunoglobulin treatment even if the effective mechanism of action can still only be hypothesised. PMID- 1620078 TI - [Several aspects of the treatment of HIV infections]. PMID- 1620079 TI - [AIDS in transplant recipients]. PMID- 1620080 TI - [Nocardiosis and AIDS]. PMID- 1620081 TI - Taking the guesswork out of bloodborne pathogen regulations? PMID- 1620082 TI - BNDD complaints. PMID- 1620083 TI - Fast, good, and cheap. PMID- 1620084 TI - Cry of the heart. Reflections of a practitioner. PMID- 1620085 TI - HCFA survey form. PMID- 1620086 TI - Research on ticks and tickborne pathogens in Missouri--an interim research report. PMID- 1620087 TI - A blueprint for reform in medical education. PMID- 1620088 TI - Isolated traumatic accessory splenic rupture: a case report and literature review. AB - Although small and relatively protected, an accessory spleen can be the cause of acute intraabdominal symptoms following minimal trauma. Although a splenic fracture or laceration may not be apparent on by CT scan, the scan cannot rule out the possibility. The diagnosis of splenic injury should be entertained in light of appropriate history and physical findings. The case we present and prior similar cases are a useful review of isolated accessory splenic rupture due to blunt trauma. PMID- 1620089 TI - Kayaking as a risk factor for leptospirosis. AB - Leptospirosis is a common zoonosis present throughout Missouri. Previously regarded as an occupational illness of farmers and sewer workers, it is now primarily acquired from exposure to water polluted with the bacteria Leptospira. We present a case report of leptospirosis acquired through kayaking and review both the disease and the risk factor associated with kayaking. PMID- 1620090 TI - Aggressive rehabilitation following anterior cruciate reconstruction: an update and protocol. AB - Dramatic changes in anterior cruciate ligament (ACL) reconstruction surgery and rehabilitation methods have occurred during the past few years. These developments are reviewed briefly, and a rapid rehabilitation protocol is presented which facilitates the safe return of the patient to his or her pre operative functional level in sports and activities of daily living. PMID- 1620091 TI - Mutagenesis after exposure of bacteria to ultraviolet light and delayed photoreversal. AB - The induction of mutations by ultraviolet light and delayed photoreversal in bacteria defective for SOS mutagenesis is discussed in terms of two models: the two-step misincorporation and bypass model, and the model involving simple deamination of cytosine-containing dimers. In phage S13 the latter appears to be the predominant mechanism. In Escherichia coli there is little evidence that the simple deamination mechanism is of any significance except in ung strains lacking uracil glycosylase where uracils left after photoreversal are not removed. Deamination might, however, occur during the operation of translesion synthesis via the two-step model and if it did, subsequent photoreversal would lead to the "mutation" being extended from one to both strands by uracil glycosylase repair rather than being removed. PMID- 1620092 TI - Survival of phage M13 with uracils on one or both DNA strands. AB - The survival of M13 DNA was studied after partial replacement of thymine by uracil in the bacteriophage. Uracils carry the same genetic information as the thymines. Nevertheless in Escherichia coli wild-type cells, uracils in DNA are replaced by thymines by excision repair initiated by uracil-DNA glycosylase (UDG). Thus inactivation of uracil-containing phage DNA is solely due to repair initiated by UDG. Incorporation of uracils was achieved in one or in both strands, either randomly or site-specifically using differently uracylated oligonucleotides. The results show that up to 580 uracils can be repaired without a significant decrease in survival if the uracils are localized in the (-) strand only. Incorporation of 246 uracils into the (+) strand leads to approximately 30% or approximately 10% survival when expressed in Escherichia coli strains CMK and JM103, respectively. However, when uracils are distributed over both strands a sharp decrease in survival occurs. This shows that the repair of two uracils localized in close proximity on opposite strands of the DNA by the excision repair mechanism is difficult, whereas uracils occurring in one strand are repaired more efficiently, irrespective of their number. PMID- 1620093 TI - Identification of a site required for DNA replication fork blocking activity in the rRNA gene cluster in Saccharomyces cerevisiae. AB - The yeast genome has DNA replication fork blocking sites, that we have named sog sites, in the ribosomal RNA gene (rDNA) cluster. These are located at the 3' end of the 35S rRNA transcription unit and they block replication fork movement in a direction opposite to that of RNA polymerase I. We cloned this replication blocking site into a YEp-type plasmid and analyzed DNA replication intermediates, using two-dimensional (2D) agarose gel electrophoresis. The blocking activity remained even on a plasmid not involved in 35S rRNA transcription and inhibited fork movement in the same polar fashion as on the yeast chromosome. To define the site further, smaller fragments were subcloned into the YEp-type plasmid. A small 109 bp region exhibited sog activity and was located near the enhancer region for 35S rRNA transcription. It overlaps an essential element of the recombinational hot spot HOT1. PMID- 1620094 TI - A new member of the adenylate kinase family in yeast: PAK3 is highly homologous to mammalian AK3 and is targeted to mitochondria. AB - Making use of the polymerase chain reaction primed by oligonucleotides corresponding to regions conserved between members of the nucleoside monophosphate kinase family, we have isolated the yeast gene PAK3. Pak3p belongs to the subgroup of long-form adenylate kinase isozymes (deduced molecular mass 25.3 kDa) and exhibits highest sequence similarity to bovine AK3 rather than to the yeast isozyme, Aky2p. The gene is shown to be non-essential because haploid disruption mutants are viable, both in the presence and absence of a functional AKY2 allele. It maps on chromosome V upstream of RAD3. Its expression level is low when cells are grown on glucose or other fermentable carbon sources and about threefold higher on glycerol, but can be significantly induced by ethanol. A PAK3/mouse dihydrofolate reductase fusion construct expressed in yeast is targeted to mitochondria. Transformation with PAK3 on a multicopy plasmid complements neither adenylate kinase deficiency in an aky2-disrupted yeast strain nor in Escherichia coli cells conditionally defective in adenylate kinase. PMID- 1620095 TI - Regulated transcription of the maize Bronze-2 promoter in electroporated protoplasts requires the C1 and R gene products. AB - The putative maize transcription factor genes R and C1 are required for expression of reporter genes with promoters from the Bz1 and A1 genes, which encode enzymes required for anthocyanin biosynthesis in maize. Bz2 is another anthocyanin biosynthetic gene; we show that expression of a reporter gene from the Bz2 promoter also requires R and C1 when the fusion construct is introduced into maize kernels by particle gun bombardment. When electroporated into maize protoplasts from a suspension cell line not synthesizing anthocyanins, reporter genes with Bz2, Bz1, and A1 promoters are expressed only when both R and C1 expression plasmids are co-electroporated. Electroporation of R and C1 expression plasmids also induces the endogenous genes required for anthocyanin synthesis, resulting in pink protoplasts within 24 h. RNase protection analysis demonstrates that accumulation of mRNA from the endogenous Bz1 and Bz2 genes absolutely requires introduced R and C1. In time-course experiments there is a delay of 3-6 h before the Bz2 promoter is activated, supporting the proposed role for R- and C1-encoded proteins in transcriptional control. An excess of R relative to C1 suppresses expression of A1, Bz1, and Bz2 promoters, suggesting an interaction between the R and C1 proteins. PMID- 1620096 TI - Immunity and resistance to the KP6 toxin of Ustilago maydis. AB - The KP6 toxin of Ustilago maydis, encoded by segmented double-stranded (ds) RNA viruses, is lethal to sensitive strains of the same species and related species. The toxin consists of two polypeptides, alpha and beta, synthesized as a single preprotoxin, which are not covalently linked. Neither polypeptide alone is toxic, but killer activity can be restored by in vitro and in vivo complementation. Killer-secreting strains are resistant to the toxin they produce. Resistance is conferred by a single recessive nuclear gene. This study describes a search for cytoplasmic factors that may confer resistance, also referred to as immunity. The approaches used to detect cytoplasmic immunity included transmission of dsRNA and transmission of virus particles to sensitive cells by cytoduction, cytoplasmic mixing in diploids and infection with viruses. An alternative approach was also used to express cloned cDNAs of the KP6 toxin-encoding dsRNA and of the alpha and beta polypeptides. The results indicated that no immunity to KP6 can be detected. While KP6, alpha and beta polypeptides were expressed by resistant cells, neither KP6 nor beta were expressed in sensitive strains. The alpha polypeptide was expressed in sensitive cells, but it did not confer immunity. These results suggest that neither the preprotoxin nor the alpha or beta polypeptides confer immunity and thus beta may be the toxic component of the binary toxin. PMID- 1620097 TI - Analysis of an upstream regulatory sequence required for activation of the regulatory gene xylS in xylene metabolism directed by the TOL plasmid of Pseudomonas putida. AB - Transcription from the promoter of a positive regulatory gene, xylS, on the TOL plasmid of Pseudomonas putida is activated by another positive regulator, XylR, in the presence of m-xylene and is dependent on RNA polymerase containing the NtrA protein (sigma 54). Deletion analysis of the upstream region of the xylS gene revealed an upstream regulatory sequence (URS), located between 145 and 188 bp upstream from the transcription start site. The URS is active in either orientation and can be placed 3.9 kb further upstream without loss of activity. Dependence of activation on helical periodicity was observed in the region between the URS and the promoter of the xylS gene, suggesting DNA loop formation between these two sites, which are located about 100 bp apart. The expression of xylR was autogenously repressed by XylR protein. This autogenous repression is decreased in an NtrA- background, irrespective of the presence of the xylS promoter in cis, indicating that NtrA protein, or NtrA-containing RNA polymerase that is not bound to the xylS promoter, is involved in the binding of XylR protein to the URS. PMID- 1620099 TI - The switching gene swi6 affects recombination and gene expression in the mating type region of Schizosaccharomyces pombe. AB - The products of 11 switching (swi) genes are required for efficient mating-type (MT) switching in homothallic (h90) strains of Schizosaccharomyces pombe. The MT region of h90 comprises three cassette genes: the expression site mat1:1 and two silent loci, mat2:2 and mat3:3. Besides reducing MT switching, the swi6 mutation leads to deletions in the MT region caused by intrachromosomal cross-overs between two paired cassettes. These deletions only arise if DNA double-strand breaks are present at mat1:1, which initiate MT switching. Furthermore, swi6 allows meiotic recombination in the K region, a region of 16 kb between mat2:2 and mat3:3; in wild-type strains no recombination occurs in K. swi6 also allows the simultaneous expression of two different cassettes in the same haploid cell. Thus swi6 may have an influence on the general chromatin structure in the MT region. PMID- 1620098 TI - Herbicide resistance due to amplification of a mutant acetohydroxyacid synthase gene. AB - We have selected a tobacco cell line, SU-27D5, that is highly resistant to sulfonylurea and imidazolinone herbicides. This line was developed by selection first on a lethal concentration of cinosulfuron and then on increasing concentrations of primisulfuron, both sulfonylurea herbicides. SU-27D5 was tested against five sulfonylureas and one imidazolinone herbicide and was shown, in every case, to be two to three orders of magnitude more resistant than wild-type cells. The acetohydroxyacid synthase (AHAS) of SU-27D5 was 50- to 780-fold less sensitive than that of wild-type cells to herbicide inhibition. The specific activity of AHAS in the SU-27D5 cell lysate was 6 to 7 times greater than that in wild-type cells. Using Southern analysis, we showed that cell line SU-27D5 had amplified its SuRB AHAS gene about 20-fold while maintaining a normal diploid complement of the SuRA AHAS gene. Genomic clones of both AHAS genes were isolated and used to transform wild-type tobacco protoplasts. SuRB clones gave rise to herbicide-resistant transformants, whereas SuRA clones did not. DNA sequencing showed that all SuRB clones contained a point mutation at nucleotide 588 that converted amino acid 196 of AHAS from proline to serine. In contrast, no mutations were found in the SuRA clones. The stability of SuRB gene amplification was variable in the absence of selection. In one experiment, the withdrawal of selection reduced the copy number of the amplified SuRB gene to the normal level within 30 days. In another experiment, amplification remained stable after extended cultivation on herbicide-free medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620101 TI - Transfer of defined numbers of chloroplasts into albino protoplasts by subprotoplast/protoplast microfusion: chloroplasts can be "cloned", by using suitable plastome combinations or selective pressure. AB - Defined numbers (1-5) of (donor) chloroplasts were transferred into (acceptor) protoplasts of plastid albino mutants by subprotoplasts/protoplast microfusion. Single transferred plastids gave rise to new organelle populations in the progeny of the fusion products when suitable combinations of plastomes were used or when selective pressure for the plastome transferred was applied. This process is termed "chloroplast cloning" and is the first reported case of "cloning" a cell organelle. The plastome combination and the presence or absence of selective pressure were found to influence the frequencies with which cell lines, containing both plastomes or acceptor or donor only, were obtained, and the number of cell generations needed for complete segregation - as measured by the duration of culture before the green donor plastome could be detected. The high frequency of cell lines and regenerated shoots recovered with donor plastome only, even when only a single chloroplast was transferred, leads to the conclusion that all organelles present in the fusion product contribute to the organelle population of the progeny, i.e. organelle death or loss are not regularly occurring events during plant regeneration from protoplasts in Nicotiana tabacum. PMID- 1620100 TI - Molecular characterisation of inter- and intra-specific somatic hybrids of potato using randomly amplified polymorphic DNA (RAPD) markers. AB - Protoplast fusion allows the transfer of both mono- and polygenic traits between species that are sexually incompatible. This approach has particular relevance for potato, and somatic hybridisation has been used to introduce a range of disease resistance genes from sexually incompatible wild species into the cultivated potato gene pool. In addition, protoplast fusion allows the resynthesis of tetraploid genotypes from preselected diploid or dihaploid donor parents. A limiting factor for the efficient exploitation of this technology in potato breeding is the difficulty of unequivocally identifying nuclear hybrids (heterokaryons). In order to facilitate the identification of hybrids at an early stage following fusion, Randomly Amplified Polymorphic DNA markers (RAPDs) have been used to characterise molecularly both inter- and intra-specific somatic hybrids of potato. RAPD markers detect naturally occurring polymorphism in the donor genotypes and utilise short oligonucleotide primers of arbitrary nucleotide sequence in combination with the polymerase chain reaction (PCR). The exploitation of RAPDs in the characterisation of both somatic and sexual hybrids is discussed. PMID- 1620102 TI - Riboflavin operon of Bacillus subtilis: unusual symmetric arrangement of the regulatory region. AB - Seventeen cis-dominant mutations leading to riboflavin overproduction in Bacillus subtilis were localized to the region between nucleotides +37 and +159 relative to the transcription initiation site of the riboflavin operon. This region displays an unusual structure for regulatory sequences. The main part of it represents clusters of A/T and G/C-rich sequences that symmetrically blank a short inverted repeat. PMID- 1620103 TI - The two genes encoding protein synthesis initiation factor eIF-5A in Saccharomyces cerevisiae are members of a duplicated gene cluster. AB - Translation initiation factor eIF-5A is an abundant protein in which a lysine residue is modified by spermidine to form the amino acid derivative, hypusine. The factor is encoded by two genes in Saccharomyces cerevisiae, called TIF51A and TIF51B, which are regulated reciprocally by oxygen and by heme. TIF51B, also called ANB1, is located on chromosome X in a region called COR. We physically mapped TIF51A and its associated serine tRNA2 gene by the method of chromosome fragmentation and pulsed-field gel electrophoresis. TIF51A maps 90 kb from the left end of chromosome V in a region called ARC. The COR and ARC regions contain CYC1 and CYC7, respectively, and appear to be duplications carrying numerous related genes. The arrangements of related genes in the two regions are incompatible with a duplication mechanism involving a circular intermediate. PMID- 1620104 TI - Molecular structure and evolution of double-minute chromosomes in methotrexate resistant cultured mouse cells. AB - To determine whether microscopically visible double-minute chromosomes (DMs) are derived from submicroscopic precursors, we monitored the amplification of the dihydrofolate reductase (DHFR) gene in 10 independent isolates of methotrexate (MTX)-resistant mouse cells. At every other doubling in MTX concentration, the cells were examined both microscopically, to detect the presence of microscopically visible DMs, and by pulsed-field gel electrophoresis and hybridization to a DHFR-specific probe, to detect submicroscopic DMs. One of the cloned MTX-resistant isolates was examined in detail and was shown to originally contain amplified DHFR genes on circular DMs measuring 1 and 3 Mb in size; additionally, metaphase chromosome preparations from this cloned isolate were examined and were shown to contain microscopically visible DMs too large to enter a pulsed-field gel. During stepwise selection for increasing levels of MTX, the smaller DMs (not microscopically visible) were shown to be preferentially amplified, whereas the larger (microscopically visible) ones decreased in relative numbers. Rare-cutting NotI digestion patterns of total genomic DNA that includes the DMs containing the DHFR gene suggest that the DMs increase in copy number without any further significant rearrangements. We saw no evidence from any of the 10 isolates to suggest that microscopically visible DMs are formed from smaller submicroscopic precursors. PMID- 1620105 TI - High-fidelity gene targeting in embryonic stem cells by using sequence replacement vectors. AB - Mutations were targeted to the Hprt locus in murine embryonic stem cells by using sequence replacement vectors. When the vector was designed such that the mutated sequences were flanked on both sides by several kilobases of DNA homologous to the target locus, replacement of chromosomal sequences with the exogenous DNA occurred with precision. If, on the other hand, the target-homologous DNA on one arm of the vector was reduced to below 1 kb in length, the fidelity of recombination was diminished. PMID- 1620106 TI - U-rich sequence-binding proteins (URBPs) interacting with a 20-nucleotide U-rich sequence in the 3' untranslated region of c-fos mRNA may be involved in the first step of c-fos mRNA degradation. AB - Rapid decay of the c-fos transcript plays a critical role in controlling transforming potential of the c-fos proto-oncogene. One of the mRNA instability determinants is a 75-nucleotide AU-rich element (ARE) present in the 3' untranslated region of the c-fos transcript. It appears to control two steps in the process of c-fos mRNA degradation: removal of the poly(A) tail, which does not require the AUUUA motifs, and subsequent degradation of deadenylated mRNA, which appears to be dependent on the AUUUA motifs. In this study, we report the identification of four U-rich sequence binding proteins (URBPs) that specifically interact with a 20-nucleotide U-rich sequence within the c-fos ARE. Gel mobility shift assay and competition experiments showed that these protein factors form three specific band-shifted complexes with the c-fos ARE. Binding activity of one of the protein factors, a 37-kDa protein, is significantly affected by serum induction and by pretreatment of cells with drugs known to stabilize many of the immediate-early gene mRNAs. Combining UV cross-linking with a new approach, designated sequential RNase digestion, we were able to better determine the molecular masses of these cellular proteins. The binding sites for the four proteins were all mapped to a 20-nucleotide U-rich sequence located at the 3' half of the c-fos ARE, which contains no AUUUA pentanucleotides but stretches of uridylate residues. Single U-to-A point mutations in each of the three AUUUA motifs within the c-fos ARE have little effect on formation of the mobility shifted complexes. Our data indicate c-fos ARE-protein interaction involves recognition of U stretches rather than recognition of the AUUUA motifs. We propose that UTBP binding may be involved in the first step, removal of the Poly(A) tail, in the c-fos ARE-mediated decay pathway. PMID- 1620107 TI - Control of mRNA turnover as a mechanism of glucose repression in Saccharomyces cerevisiae. AB - We have examined the expression of the gene encoding the iron-protein subunit (Ip) of succinate dehydrogenase in Saccharomyces cerevisiae. The gene had been cloned by us and shown to be subject to glucose regulation (A. Lombardo, K. Carine, and I. E. Scheffler, J. Biol. Chem. 265:10419-10423, 1990). We discovered that a significant part of the regulation of the Ip mRNA levels by glucose involves the regulation of the turnover rate of this mRNA. In the presence of glucose, the half-life appears to be less than 5 min, while in glycerol medium, the half-life is greater than 60 min. The gene is also regulated transcriptionally by glucose. The upstream promoter sequence appeared to have four regulatory elements with consensus sequences shown to be responsible for the interaction with the HAP2/3/4 regulatory complex. A deletion analysis has shown that the two distal elements are redundant. These measurements were carried out by Northern (RNA) analyses of Ip mRNA transcripts as well as by assays of beta galactosidase activity in cells carrying constructs of the Ip promoter linked to the lacZ coding sequence. These observations on the regulation of mRNA stability were also extended to the mRNA of the flavoprotein subunit of succinate dehydrogenase and in some experiments of iso-1-cytochrome c. PMID- 1620108 TI - Putative GTP-binding protein, Gtr1, associated with the function of the Pho84 inorganic phosphate transporter in Saccharomyces cerevisiae. AB - We have found an open reading frame which is 1.1 kb upstream of PHO84 (which encodes a Pi transporter) and is transcribed from the opposite strand. In Saccharomyces cerevisiae, this gene is distal to the TUB3 locus on the left arm of chromosome XIII and is named GTR1. GTR1 encodes a protein consisting of 310 amino acid residues containing, in its N-terminal region, the characteristic tripartite consensus elements for binding GTP conserved in GTP-binding proteins, except for histidine in place of a widely conserved aspargine residue in element III. Disruption of the GTR1 gene resulted in slow growth at 30 degrees C and no growth at 15 degrees C; other phenotypes resembled those of pho84 mutants and included constitutive synthesis of repressible acid phosphatase, reduced Pi transport activity, and resistance to arsenate. The latter phenotypes were shown to be due to a defect in Pi uptake, and the Gtr1 protein was found to be functionally associated with the Pho84 Pi transporter. Recombination between chromosome V (at the URA3 locus) and chromosome XIII (in the GTR1-PHO84-TUB3 region) by using a plasmid-encoded site-specific recombination system indicated that the order of these genes was telomere-TUB3-PHO84-GTR1-CENXIII. PMID- 1620109 TI - Role of the PU.1 transcription factor in controlling differentiation of Friend erythroleukemia cells. AB - Both viral and cellular genes have been directly implicated in pathogenesis of Friend viral erythroleukemia. The virus-encoded gp55 glycoprotein binds to erythropoietin receptors to cause mitogenesis and differentiation of erythroblasts. However, if the provirus integrates adjacent to the gene for the PU.1 transcription factor, the cell loses its commitment to terminally differentiate and becomes immortal, as indicated by its transplantability and by its potential for indefinite growth in culture (C. Spiro, B. Gliniak, and D. Kabat, J. Virol. 63:4434-4437, 1989; R. Paul, S. Schuetze, S. L. Kozak, and D. Kabat, J. Virol. 65:464-467, 1991). To test the implications of these results, we produced polyclonal antiserum to bacterially synthesized PU.1, and we used it to analyze PU.1 expression throughout leukemic progression and during chemically induced differentiation of Friend erythroleukemia (F-MEL) cell lines. This antiserum identified three electrophoretically distinct PU.1 components in extracts of F-MEL cells and demonstrated their nuclear localization. Although PU.1 proteins are abundant in F-MEL cells, they are absent or present in only trace amounts in normal erythroblasts or in differentiating erythroblasts from the preleukemic stage of Friend disease. Furthermore, chemicals (dimethyl sulfoxide or N,N'-hexamethylenebisacetamide) that overcome the blocked differentiation of F-MEL cells induce rapid declines of PU.1 mRNA and PU.1 proteins. The elimination of PU.1 proteins coincides with recommitment to the program of erythroid differentiation and with loss of immortality. These results support the hypothesis that PU.1 interferes with the commitment of erythroblasts to differentiate and that chemicals that reduce PU.1 expression reinstate the erythropoietic program. PMID- 1620110 TI - Transcription of the gene for a pepsinogen, PEP1, is regulated by white-opaque switching in Candida albicans. AB - Cells of Candida albicans WO-1 spontaneously switch between a white and opaque CFU, and this phase transition involves a dramatic change in cellular phenotype. By using a differential hybridization screen, an opaque-specific cDNA, Op1a, which represents the transcript of a gene regulated by switching, has been isolated. The gene for Op1a is transcribed by opaque but not by white cells. The nucleotide sequence of the Op1a cDNA reveals over 99% base homology with an acid protease gene of C. albicans, and the predicted amino acid sequence demonstrates that the product of this gene is a member of the family of pepsinogens, which possess a hydrophobic leader sequence for secretion and two catalytic aspartate domains. Southern blots of both genomic DNA digested with 14 different endonucleases and electrophoretically separated chromosomes were probed with the Op1a cDNA. No polymorphisms were detected in either case between white and opaque cells, suggesting that no genomic reorganization occurs in the proximity of the gene during the white-opaque transition. Although transcription of Op1a correlates with the high levels of extracellular protease activity in opaque cell cultures and the absence of activity in white cell cultures, stimulation of extracellular protease activity by addition of serum albumin is not accompanied by Op1a transcription in cultures of WO-1 white cells or cultures of two additional clinical isolates of C. albicans, suggesting that expression of one or more other protease genes is stimulated in these cases. The results demonstrate that transcription of the Op1a gene is under the rigid control of switching in strain WO-1. PMID- 1620111 TI - Fused protein domains inhibit DNA binding by LexA. AB - Many studies of transcription activation employ fusions of activation domains to DNA binding domains derived from the bacterial repressor LexA and the yeast activator GAL4. Such studies often implicitly assume that DNA binding by the chimeric proteins is equivalent to that of the protein donating the DNA binding moiety. To directly investigate this issue, we compared operator binding by a series of LexA-derivative proteins to operator binding by native LexA, by using both in vivo and in vitro assays. We show that operator binding by many proteins such as LexA-Myc, LexA-Fos, and LexA-Bicoid is severely impaired, while binding of other LexA-derivative proteins, such as those that carry bacterially encoded acidic sequences ("acid blobs"), is not. Our results also show that DNA binding by LexA derivatives that contain the LexA carboxy-terminal dimerization domain (amino acids 88 to 202) is considerably stronger than binding by fusions that lack it and that heterologous dimerization motifs cannot substitute for the LexA88-202 function. These results suggest the need to reevaluate some previous studies of activation that employed LexA derivatives and modifications to recent experimental approaches that use LexA and GAL4 derivatives to detect and study protein-protein interactions. PMID- 1620112 TI - Modulation of ferritin H-chain expression in Friend erythroleukemia cells: transcriptional and translational regulation by hemin. AB - The mechanisms that regulate the expression of the H chain of the iron storage protein ferritin in Friend erythroleukemia cells (FLCs) after exposure to hemin (ferric protoporphyrin IX), protoporphyrin IX, and ferric ammonium citrate (FAC) have been investigated. Administration of hemin increases the steady-state level of ferritin mRNA about 10-fold and that of ferritin protein expression 20-fold. Experiments with the transcriptional inhibitor actinomycin D and transfection studies demonstrate that the increment in cytoplasmic mRNA content results from enhanced transcription of the ferritin H-chain gene and cannot be attributed to stabilization of preexisting mRNAs. In addition to transcriptional effects, translational regulation induces the recruitment of stored mRNAs into functional polyribosomes after hemin and FAC administration, resulting in a further increase in ferritin synthesis. Administration of protoporphyrin IX to FLCs produces divergent transcriptional and translational effects. It increases transcription but appears to suppress ferritin mRNA translation. FAC treatment increases the mRNA content slightly (about twofold), and the ferritin levels rise about fivefold over the control values. We conclude that in FLCs, hemin induces ferritin H-chain biosynthesis by multiple mechanisms: a transcriptional mechanism exerted also by protoporphyrin IX and a translational one, not displayed by protoporphyrin IX but shared with FAC. PMID- 1620113 TI - Temporal expression of the human alcohol dehydrogenase gene family during liver development correlates with differential promoter activation by hepatocyte nuclear factor 1, CCAAT/enhancer-binding protein alpha, liver activator protein, and D-element-binding protein. AB - The human class I alcohol dehydrogenase (ADH) gene family consists of ADH1, ADH2, and ADH3, which are sequentially activated in early fetal, late fetal, and postnatal liver, respectively. Analysis of ADH promoters revealed differential activation by several factors previously shown to control liver transcription. In cotransfection assays, the ADH1 promoter, but not the ADH2 or ADH3 promoter, was shown to respond to hepatocyte nuclear factor 1 (HNF-1), which has previously been shown to regulate transcription in early liver development. The ADH2 promoter, but not the ADH1 or ADH3 promoter, was shown to respond to CCAAT/enhancer-binding protein alpha (C/EBP alpha), a transcription factor particularly active during late fetal liver and early postnatal liver development. The ADH1, ADH2, and ADH3 promoters all responded to the liver transcription factors liver activator protein (LAP) and D-element-binding protein (DBP), which are most active in postnatal liver. For all three promoters, the activation by LAP or DBP was higher than that seen by HNF-1 or C/EBP alpha, and a significant synergism between C/EBP alpha and LAP was noticed for the ADH2 and ADH3 promoters when both factors were simultaneously cotransfected. A hierarchy of ADH promoter responsiveness to C/EBP alpha and LAP homo- and heterodimers is suggested. In all three ADH genes, LAP bound to the same four sites previously reported for C/EBP alpha (i.e., -160, -120, -40, and -20 bp), but DBP bound strongly only to the site located at -40 bp relative to the transcriptional start. Mutational analysis of ADH2 indicated that the -40 bp element accounts for most of the promoter regulation by the bZIP factors analyzed. These studies suggest that HNF-1 and C/EBP alpha help establish ADH gene family transcription in fetal liver and that LAP and DBP help maintain high-level ADH gene family transcription in postnatal liver. PMID- 1620114 TI - Stable and specific association between the yeast recombination and DNA repair proteins RAD1 and RAD10 in vitro. AB - The RAD1 and RAD10 genes of Saccharomyces cerevisiae are two of at least seven genes which are known to be required for damage-specific recognition and/or damage-specific incision of DNA during nucleotide excision repair. RAD1 and RAD10 are also involved in a specialized mitotic recombination pathway. We have previously reported the purification of the RAD10 protein to homogeneity (L. Bardwell, H. Burtscher, W. A. Weiss, C. M. Nicolet, and E. C. Friedberg, Biochemistry 29:3119-3126, 1990). In the present studies we show that the RAD1 protein, produced by in vitro transcription and translation of the cloned gene, specifically coimmunoprecipitates with the RAD10 protein translated in vitro or purified from yeast. Conversely, in vitro-translated RAD10 protein specifically coimmunoprecipitates with the RAD1 protein. The sites of this stable and specific interaction have been mapped to the C-terminal regions of both polypeptides. This portion of RAD10 protein is evolutionarily conserved. These results are the first biochemical evidence of a specific association between any eukaryotic proteins genetically identified as belonging to a recombination or DNA repair pathway and suggest that the RAD1 and RAD10 proteins act at the same or consecutive biochemical steps in both nucleotide excision repair and mitotic recombination. PMID- 1620115 TI - Genome digestion is a dispensable consequence of physiological cell death mediated by cytotoxic T lymphocytes. AB - We examined virally transformed murine fibroblast clones as targets for cytotoxic T lymphocyte (CTL)-triggered lysis and genome digestion. Strikingly, while all clones were essentially equivalent in the ability to be lysed, one clone, SV3T3 B2.1, failed to exhibit genome digestion associated with CTL attack. Other aspects of the physiological cell death process, including loss of adhesion and nuclear envelope breakdown (lamin phosphorylation and solubilization), were not altered in this clone. The absence of genome digestion associated with CTL induced cell death correlated with the absence of endodeoxyribonuclease activity in the nuclei of that clone. Characterization of the activity affected identifies a calcium-dependent, DNase I-like endonuclease of approximately 40 kDa, normally present constitutively in all cell nuclei, as the enzyme responsible for genome digestion associated with CTL-mediated cell death. These observations indicate that neither genome digestion per se nor its consequences [such as activation of poly(ADP-ribose) polymerase] are essential for cell death resulting from the triggering of this cell suicide process. PMID- 1620117 TI - In vivo function of regulatory DNA sequence elements of a major histocompatibility complex class I gene. AB - Major histocompatibility complex class I genes are expressed in nearly all somatic tissues, although their level of expression varies. By analysis of a set of promoter deletion mutants introduced into transgenic mice, a complex regulatory element, consisting of overlapping enhancer and silencer activities, is demonstrated to function as a tissue-specific regulator of class I expression. The enhancer activity predominates in lymphoid tissues but not in nonlymphoid tissues. In contrast to the tissue-specific functions of the complex regulatory element, a second novel silencer element is shown to function in both lymphoid and nonlymphoid tissues. The complement of DNA-binding factors in different cell lines is shown to correlate with the levels of class I expression. PMID- 1620116 TI - Transcriptional repression by a novel member of the bZIP family of transcription factors. AB - We describe here a novel member of the bZIP family of DNA-binding proteins, designated E4BP4, that displays an unusual DNA-binding specificity which overlaps that of the activating transcription factor family of factors. When expressed in a transient transfection assay with a suitable reporter plasmid, E4BP4 strongly repressed transcription in a DNA-binding-site-dependent manner. Examination of a series of deletion mutants revealed that sequences responsible for the repressing potential of E4BP4 lie within the carboxyl-terminal region of the protein. No similarity was found between this region and the repressing domains of other known eukaryotic transcriptional repressors. PMID- 1620118 TI - The RxxRxRxxC motif conserved in all Rel/kappa B proteins is essential for the DNA-binding activity and redox regulation of the v-Rel oncoprotein. AB - The v- and c-Rel oncoproteins bind to oligonucleotides containing kappa B motifs, form heterodimers with other members of the Rel family, and modulate expression of genes linked to kappa B motifs. Here, we report that the RxxRxRxxC motif conserved in all Rel/kappa B family proteins is absolutely required for v-Rel protein-DNA contact and its resulting transforming activity. We also demonstrate that serine substitution of the cysteine residue conserved within this motif enables v-Rel to escape redox control, thereby promoting overall DNA binding. These mutant proteins retained the ability to competitively inhibit kappa B mediated transcriptional activation of the human immunodeficiency virus long terminal repeat but failed to efficiently transform chicken lymphoid cells both in vitro and in vivo. Our data indicate that reduction of the conserved cysteine residue in the RxxRxRxxC motif may be required for optimal DNA-protein interactions. These results provide direct biochemical evidence that the DNA binding activity of v-Rel is subject to redox control and that the conserved cysteine residue in the RxxRxRxxC motif is critical for this regulation. These studies suggest that the DNA-binding, transcriptional, and biological activities of Rel family proteins may also be subject to redox control in vivo. PMID- 1620119 TI - Oct2 transactivation from a remote enhancer position requires a B-cell-restricted activity. AB - Previous cotransfection experiments had demonstrated that ectopic expression of the lymphocyte-specific transcription factor Oct2 could efficiently activate a promoter containing an octamer motif. Oct2 expression was unable to stimulate a multimerized octamer enhancer element in HeLa cells, however. We have tested a variety of Oct2 isoforms generated by alternative splicing for the capability to activate an octamer enhancer in nonlymphoid cells and a B-cell line. Our analyses show that several Oct2 isoforms can stimulate from a remote position but that this stimulation is restricted to B cells. This result indicates the involvement of either a B-cell-specific cofactor or a specific modification of a cofactor or the Oct2 protein in Oct2-mediated enhancer activation. Mutational analyses indicate that the carboxy-terminal domain of Oct2 is critical for enhancer activation. Moreover, this domain conferred enhancing activity when fused to the Oct1 protein, which by itself was unable to stimulate from a remote position. The glutamine-rich activation domain present in the amino-terminal portion of Oct2 and the POU domain contribute only marginally to the transactivation function from a distal position. PMID- 1620120 TI - Activation domains of L-Myc and c-Myc determine their transforming potencies in rat embryo cells. AB - Members of the Myc family of proteins share a number of protein motifs that are found in regulators of gene transcription. Conserved stretches of amino acids found in the N-terminal transcriptional activation domain of c-Myc are required for cotransforming activity. Most of the Myc proteins contain the basic helix loop-helix zipper (bHLH-Zip) DNA-binding motif which is also required for the cotransforming activity of c-Myc. L-Myc, the product of a myc family gene that is highly amplified in many human lung carcinomas, was found to cotransform primary rat embryo cells with an activated ras gene. However, L-Myc cotransforming activity was only 1 to 10% of that of c-Myc (M. J. Birrer, S. Segal, J. S. DeGreve, F. Kaye, E. A. Sausville, and J. D. Minna, Mol. Cell. Biol. 8:2668-2673, 1988). We sought to determine whether functional differences between c-Myc and L Myc in either the N-terminal or the C-terminal domain could account for the relatively diminished L-Myc cotransforming activity. Although the N-terminal domain of L-Myc could activate transcription when fused to the yeast GAL4 DNA binding domain, the activity was only 5% of that of a comparable c-Myc domain. We next determined that the interaction of the C-terminal bHLH-Zip region of L-Myc or c-Myc with that of a Myc partner protein, Max, was equivalent in transfected cells. A Max expression vector was found to augment the cotransforming activity of L-Myc as well as that of c-Myc. In addition, a bacterially synthesized DNA binding domain of L-Myc, like that o c-Myc, heterodimerizes with purified Max protein to bind the core DNA sequence CACGTG. To determine the region of L-Myc responsible for its relatively diminished cotransforming activity, we constructed chimeras containing exons 2 (constituting activation domains) and 3 (constituting DNA-binding domains) of c-Myc fused to those of L-Myc. The cotransforming potencies of these chimeras were compared with those of full-length L-Myc of c Myc in rat embryo cells. The relative cotransforming activities suggest that the potencies of the activation domains determine the cotransforming efficiencies for c-Myc and L-Myc. This correlation supports the hypothesis that the Myc proteins function in neoplastic cotransformation as transcription factors. PMID- 1620121 TI - Growth-regulated expression of rhoG, a new member of the ras homolog gene family. AB - Cellular transition from the resting state to DNA synthesis involves master switches genes encoding transcriptional factors (e.g., fos, jun, and egr genes), whose targets remain to be fully characterized. To isolate coding sequences specifically accumulated in late G1, a differential screening was performed on a cDNA library prepared from hamster lung fibroblasts stimulated for 5 h with serum. One of the positive clones which displayed a sevenfold induction, turned out to code for a protein sharing homology to Ras-like products. Cloning and sequence analysis of the human homolog revealed that this putative new small GTPase, referred to as rhoG, is more closely related to the rac, CDC42, and TC10 members of the rho (ras homolog) gene family and might have diverged very early during evolution. rhoG mRNA accumulates in proportion to the mitogenic strength of various purified growth factors used for the stimulation, as a consequence of transcriptional activation. G1-specific RNA accumulation is impaired upon addition of antimitogenic cyclic AMP and is enhanced when protein synthesis is inhibited, mainly as a result of RNA stabilization. rhoG mRNA expression is observed in a wide variety of human organs but reaches a particularly high level in lung and placental tissues. PMID- 1620122 TI - Induction of the POU domain transcription factor Oct-2 during T-cell activation by cognate antigen. AB - Oct-2 is a transcription factor that binds specifically to octamer DNA motifs in the promoters of immunoglobulin and interleukin-2 genes. All tumor cell lines from the B-cell lineage and a few from the T-cell lineage express Oct-2. To address the role of Oct-2 in the T-cell lineage, we studied the expression of Oct 2 mRNA and protein in nontransformed human and mouse T cells. Oct-2 was found in CD4+ and CD8+ T cells prepared from human peripheral blood and in mouse lymph node T cells. In a T-cell clone specific for pigeon cytochrome c in the context of I-Ek, Oct-2 was induced by antigen stimulation, with the increase in Oct-2 protein seen first at 3 h after activation and continuing for at least 24 h. Oct 2 mRNA induction during antigen-driven T-cell activation was blocked by cyclosporin A, as well as by protein synthesis inhibitors. These results suggest that Oct-2 participates in transcriptional regulation during T-cell activation. The relatively delayed kinetics of Oct-2 induction suggests that Oct-2 mediates the changes in gene expression which occur many hours or days following antigen stimulation of T lymphocytes. PMID- 1620123 TI - Differential binding of zinc fingers from Xenopus TFIIIA and p43 to 5S RNA and the 5S RNA gene. AB - Zinc fingers are usually associated with proteins that interact with DNA. Yet in two oocyte-specific Xenopus proteins, TFIIA and p43, zinc fingers are used to bind 5S RNA. One of these, TFIIIA, also binds the 5S RNA gene. Both proteins have nine zinc fingers that are nearly identical with respect to size and spacing. We have determined the relative affinities of groups of zinc fingers from TFIIIA for both 5S RNA and the 5S RNA gene. We have also determined the relative affinities of groups of zinc fingers from p43 for 5S RNA. The primary protein regions for RNA and DNA interaction in TFIIIA are located at opposite ends of the molecule. All zinc fingers from TFIIIA participate in binding 5S RNA, but zinc fingers from the C terminus have the highest affinity. N-terminal zinc fingers are essential for binding the 5S RNA gene. In contrast, zinc fingers at the amino terminus of p43 are essential for binding 5S RNA. PMID- 1620124 TI - Differential binding of heterogeneous nuclear ribonucleoproteins to mRNA precursors prior to spliceosome assembly in vitro. AB - We have investigated the composition of the earliest detectable complex (H) assembled on pre-mRNA during the in vitro splicing reaction. We show that most of the proteins in this complex correspond to heterogeneous nuclear ribonucleoproteins (hnRNP), a set of abundant RNA-binding proteins that bind nascent RNA polymerase II transcripts in vivo. Thus, these studies establish a direct parallel between the initial events of RNA processing in vitro and in vivo. In contrast to previous studies, in which total hnRNP particles were isolated from mammalian nuclei, we determined the hnRNP composition of complexes assembled on individual RNAs of defined sequence. We found that a unique combination of hnRNP proteins is associated with each RNA. Thus, our data provide direct evidence for transcript-dependent assembly of pre-mRNA in hnRNP complexes. The observation that pre-mRNA is differentially bound by hnRNP proteins prior to spliceosome assembly suggests the possibility that RNA packaging could play a central role in the mechanism of splice site selection, as well as other posttranscriptional events. PMID- 1620125 TI - Transcriptional regulation of the apolipoprotein B100 gene: purification and characterization of trans-acting factor BRF-2. AB - Apolipoprotein B100 (apoB), the only protein of low-density lipoprotein, is produced primarily in the liver and serves as a ligand for the low-density lipoprotein receptor. Hepatic cell-specific expression of the human apoB gene is controlled by at least two cis-acting positive elements located between positions 128 and -70 (H. K. Das, T. Leff, and J.L. Breslow, J. Biol. Chem. 263:11452 11458, 1988). The distal element (-128 to -85) appears to be liver specific since it shows positive activity in HepG2 cells and negative activity in HeLa cells. The proximal element (-84 to -70) acts as a positive element in both these cell lines, and two rat liver nuclear proteins, BRF-1 and C/EBP, bind to two overlapping sites (-84 to -60 and -70 to -50, respectively). By gel mobility shift assay, we have identified a rat liver nuclear protein (BRF-2) which binds to the distal element (-128 to -85) of the apoB gene. This putative trans-acting factor has been purified to apparent homogeneity by DEAE-cellulose, heparin agarose, and DNA-specific affinity chromatography. The purified BRF-2 has an apparent molecular mass of 120 kDa and was found to specifically recognize sequence -128 to -85; BRF-2 also produced a strong hypersensitive site at nucleotide position -95 with copper-orthophenanthroline reagent. A double stranded oligonucleotide (-128 to -85) containing a 3-nucleotide (TTC) insertion between position -95 and -94 was found to abolish DNA binding by BRF-2. This result suggests that the region surrounding the hypersensitive site -95 is important for protein-DNA interaction. By using apoB promoter fragments containing various internal deletions as templates for gel mobility shift assay, the region between -104 and -85 was identified to be crucial for binding by BRF 2. We propose that BRF-2 may play an important role in the tissue-specific regulation of apoB gene transcription. PMID- 1620126 TI - In vivo splicing of the beta tropomyosin pre-mRNA: a role for branch point and donor site competition. AB - The chicken beta tropomyosin gene contains two sets of alternatively spliced, mutually exclusive exons whose utilization is developmentally regulated. Exons 6A and 6B are used in nonmuscle cells (or undifferentiated muscle cells) and skeletal muscle cells, respectively. A complex arrangement of cis-acting sequence elements is involved in alternative splicing regulation. We have performed an extensive mutational analysis on the sequence spanning the region from exon 6A to the constitutive exon 7. A large number of mutant minigenes have been tested in transfection assays of cultured myogenic cells, and the splicing products have been analyzed by cDNA polymerase chain reaction. We demonstrate that in undifferentiated myoblasts, exon 6B is skipped as a result of a negative control on its selection, while exon 6A is spliced as a default choice. We provide evidence that the focal point of such a regulation is localized in the intron upstream of exon 6B and probably involves the blockage of its associated branch point. In differentiated myotubes, in contrast, both exons are accessible to the splicing machinery. We show that the preferential choice of exon 6B in this splicing environment depends on the existence of a competition between the two exons for the flanking constitutive splice sites. We demonstrate that both the donors and the branch points of the two exons are involved in this competition. PMID- 1620127 TI - Semidominant suppressors of Srs2 helicase mutations of Saccharomyces cerevisiae map in the RAD51 gene, whose sequence predicts a protein with similarities to procaryotic RecA proteins. AB - Eleven suppressors of the radiation sensitivity of Saccharomyces cerevisiae diploids lacking the Srs2 helicase were analyzed and found to contain codominant mutations in the RAD51 gene known to be involved in recombinational repair and in genetic recombination. These mutant alleles confer an almost complete block in recombinational repair, as does deletion of RAD51, but heterozygous mutant alleles suppress the defects of srs2::LEU2 cells and are semidominant in Srs2+ cells. The results of this study are interpreted to mean that wild-type Rad51 protein binds to single-stranded DNA and that the semidominant mutations do not prevent this binding. The cloning and sequencing of RAD51 indicated that the gene encodes a predicted 400-amino-acid protein with a molecular mass of 43 kDa. Sequence comparisons revealed homologies to domains of Escherichia coli RecA protein predicted to be involved in DNA binding, ATP binding, and ATP hydrolysis. The expression of RAD51, measured with a RAD51-lacZ gene fusion, was found to be UV- and gamma-ray-inducible, with dose-dependent responses. PMID- 1620128 TI - Nucleotide sequence and transcriptional regulation of the yeast recombinational repair gene RAD51. AB - The RAD51 gene of Saccharomyces cerevisiae is required both for recombination and for the repair of DNA damage caused by X rays. Here we report the sequence and transcriptional regulation of this gene. The RAD51 protein shares significant homology (approximately 50%) over a 70-amino-acid with the RAD57 protein (J.A. Kans and R.K. Mortimer, Gene 105:139-140, 1991), the product of another yeast recombinational repair gene, and also moderate (approximately 27%), but potentially significant, homology with the bacterial RecA protein. The homologies cover a region that encodes a putative nucleotide binding site of the RAD51 protein. Sequences upstream of the coding region for RAD51 protein share homology with the damage response sequence element of RAD54, an upstream activating sequence required for damage regulation of the RAD54 transcript, and also contain two sites for restriction enzyme MluI; the presence of MluI restriction sites has been associated with cell cycle regulation. A 1.6-kb transcript corresponding to RAD51 was observed, and levels of this transcript increased rapidly after exposure to relatively low doses of X-rays. Additionally, RAD51 transcript levels were found to that of a group of genes involved primarily in DNA synthesis and replication which are thought to be coordinately cell cycle regulated. Cells arrested in early G1 were still capable of increasing levels of RAD51 transcript after irradiation, indicating that increased RAD51 transcript levels after X-ray exposure are not solely due to an X-ray-induced cessation of the cell cycle at a period when the level of RAD51 expression is normally high. PMID- 1620129 TI - Overlapping and CpG methylation-sensitive protein-DNA interactions at the histone H4 transcriptional cell cycle domain: distinctions between two human H4 gene promoters. AB - Transcriptional regulation of vertebrate histone genes during the cell cycle is mediated by several factors interacting with a series of cis-acting elements located in the 5' regions of these genes. The arrangement of these promoter elements is different for each gene. However, most histone H4 gene promoters contain a highly conserved sequence immediately upstream of the TATA box (H4 subtype consensus sequence), and this region in the human H4 gene FO108 is involved in cell cycle control. The sequence-specific interaction of nuclear factor HiNF-D with this key proximal promoter element of the H4-FO108 gene is cell cycle regulated in normal diploid cells (J. Holthuis, T.A. Owen, A.J. van Wijnen, K.L. Wright, A. Ramsey-Ewing, M.B. Kennedy, R. Carter, S.C. Cosenza, K.J. Soprano, J.B. Lian, J.L. Stein, and G.S. Stein, Science, 247:1454-1457, 1990). Here, we show that this region of the H4-FO108 gene represents a composite protein-DNA interaction domain for several distinct sequence-specific DNA-binding activities, including HiNF-D, HiNF-M, and HiNF-P. Factor HiNF-P is similar to H4TF-2, a DNA-binding activity that is not cell cycle regulated and that interacts with the analogous region of the H4 gene H4.A (F. LaBella and N. Heintz, Mol. Cell. Biol. 11:5825-5831, 1991). The H4.A gene fails to interact with factors HiNF-M and HiNF-D owing to two independent sets of specific nucleotide variants, indicating differences in protein-DNA interactions between these H4 genes. Cytosine methylation of a highly conserved CpG dinucleotide interferes with binding of HiNF-P/H4TF-2 to both the H4-FO108 and H4.A promoters, but no effect is observed for either HiNF-M or HiNF-D binding to the H4-FO108 gene. Thus, strong evolutionary conservation of the H4 consensus sequence may be related to combinatorial interactions involving overlapping and interdigitated recognition nucleotides for several proteins, whose activities are regulated independently. Our results also suggest molecular complexity in the transcriptional regulation of distinct human H4 genes. PMID- 1620130 TI - Topology and functional domains of Sec63p, an endoplasmic reticulum membrane protein required for secretory protein translocation. AB - SEC63 encodes a protein required for secretory protein translocation into the endoplasmic reticulum (ER) of Saccharomyces cerevisiae (J. A. Rothblatt, R. J. Deshaies, S. L. Sanders, G. Daum, and R. Schekman, J. Cell Biol. 109:2641-2652, 1989). Antibody directed against a recombinant form of the protein detects a 73 kDa polypeptide which, by immunofluorescence microscopy, is localized to the nuclear envelope-ER network. Cell fractionation and protease protection experiments confirm the prediction that Sec63p is an integral membrane protein. A series of SEC63-SUC2 fusion genes was created to assess the topology of Sec63p within the ER membrane. The largest hybrid proteins are unglycosylated, suggesting that the carboxyl terminus of Sec63p faces the cytosol. Invertase fusion to a loop in Sec63p that is flanked by two putative transmembrane domains produces an extensively glycosylated hybrid protein. This loop, which is homologous to the amino terminus of the Escherichia coli heat shock protein, DnaJ, is likely to face the ER lumen. By analogy to the interaction of the DnaJ and Hsp70-like DnaK proteins in E. coli, the DnaJ loop of Sec63p may recruit luminal Hsp70 (BiP/GRP78/Kar2p) to the translocation apparatus. Mutations in two highly conserved positions of the DnaJ loop and short deletions of the carboxyl terminus inactivate Sec63p activity. Sec63p associates with several other proteins, including Sec61p, a 31.5-kDa glycoprotein, and a 23-kDa protein, and together with these proteins may constitute part of the polypeptide translocation apparatus. A nonfunctional DnaJ domain mutant allele does not interfere with the formation of the Sec63p/Sec61p/gp31.5/p23 complex. PMID- 1620131 TI - Conditional defect in mRNA 3' end processing caused by a mutation in the gene for poly(A) polymerase. AB - Maturation of most eukaryotic mRNA 3' ends requires endonucleolytic cleavage and polyadenylation of precursor mRNAs. To further understand the mechanism and function of mRNA 3' end processing, we identified a temperature-sensitive mutant of Saccharomyces cerevisiae defective for polyadenylation. Genetic analysis showed that the polyadenylation defect and the temperature sensitivity for growth result from a single mutation. Biochemical analysis of extracts from this mutant shows that the polyadenylation defect occurs at a step following normal site specific cleavage of a pre-mRNA at its polyadenylation site. Molecular cloning and characterization of the wild-type allele of the mutated gene revealed that it (PAP1) encodes a previously characterized poly(A) polymerase with unknown RNA substrate specificity. Analysis of mRNA levels and structure in vivo indicate that shift of growing, mutant cells to the nonpermissive temperature results in the production of poly(A)-deficient mRNAs which appear to end at their normal cleavage sites. Interestingly, measurement of the rate of protein synthesis after the temperature shift shows that translation continues long after the apparent loss of polyadenylated mRNA. Our characterization of the pap1-1 defect implicates this gene as essential for mRNA 3' end formation in S. cerevisiae. PMID- 1620132 TI - Role of protein kinase C in T-cell antigen receptor regulation of p21ras: evidence that two p21ras regulatory pathways coexist in T cells. AB - T-lymphocyte activation via the antigen receptor complex (TCR) results in accumulation of p21ras in the active GTP-bound state. Stimulation of protein kinase C (PKC) can also activate p21ras, and it has been proposed that the TCR effect on p21ras occurs as a consequence of TCR regulation of PKC. To test the role of PKC in TCR regulation of p21ras, a permeabilized cell system was used to examine TCR regulation of p21ras under conditions in which TCR activation of PKC was blocked, first by using a PKC pseudosubstrate peptide inhibitor and second by using ionic conditions that prevent phosphatidyl inositol hydrolysis and hence diacylglycerol production and PKC stimulation. The data show that TCR-induced p21ras activation is not mediated exclusively by PKC. Thus, in the absence of PKC stimulation, the TCR was still able to induce accumulation of p21ras-GTP complexes, and this stimulation correlated with an inactivation of p21ras GTPase activating proteins. The protein tyrosine kinase inhibitor herbimycin could prevent the non-PKC-mediated, TCR-induced stimulation of p21ras. These data indicate that two mechanisms for p21ras regulation coexist in T cells: one PKC mediated and one not. The TCR can apparently couple to p21ras via a non-PKC controlled route that may involve tyrosine kinases. PMID- 1620133 TI - Analysis of a tissue-specific enhancer: ARF6 regulates adipogenic gene expression. PMID- 1620135 TI - Machado-Joseph disease: an autosomal dominant motor system degeneration. AB - Machado-Joseph disease is an autosomal dominant spinocerebellar degeneration. It expresses itself clinically with variable expression. Type one patients have early onset with a rapid progression of symptoms including spasticity, rigidity and myokymia. Type two patients are the most common phenotype with ataxia and spasticity. Type three patients develop progressive ataxia with variable amyotrophy. All patients have ophthalmoparesis and normal mental status. The neuropathology consists of neuronal loss and gliosis in the substantia nigra, motor cranial nuclei, dentate nucleus of the cerebellum, and variable neuronal loss with gliosis in the cerebellar cortex and neostriatum. The cerebral cortex is normal histologically. The inferior olivary nuclei are normal, thus separating this disease from olivopontocerebellar atrophy (OPCA). The disease has a worldwide distribution including families described in Portugal, the Azores, Spain, Italy, United States, Canada, Brazil, China, Taiwan, and Japan. The gene has not been mapped for this disease but the locus on chromosome 6p mapped for most families with OPCA has been excluded for this disorder. PMID- 1620134 TI - Mechanism and consequences of the duplication of the human C4/P450c21/gene X locus. PMID- 1620136 TI - Machado-Joseph disease in New England: clinical description and distinction from the olivopontocerebellar atrophies. AB - Experience is described in 25 patients from southern New England with Machado Joseph Disease, examined serially at annual screening clinics. The disorder is dominantly inherited, with a wide range of phenotypic variation. Core clinical features described include ataxia, nystagmus, dysarthria, facial fasciculations, and lid retraction, producing a characteristic staring expression. In addition, young onset patients have spasticity, extrapyramidal rigidity, and dystonic manifestations. Late onset patients often have distal atrophy and sensory loss. Postural instability is often an early feature. We discuss the distinction of this entity from the olivopontocerebellar atrophies. PMID- 1620137 TI - Cortical mechanisms mediating asterixis. AB - We describe a patient with chronic renal failure who suffered multifocal action induced jerks. Electromyography (EMG) recorded the typical silence of asterixis. Back-averaging the EEG activity preceding the EMG silent periods in the forearm showed a biphasic wave antedating the asterixis by 23 ms. Somatosensory evoked potentials (SEPs) after median nerve stimulation were pathologically enlarged on both hemispheres. Brain-mapping of the biphasic wave preceding asterixis and the giant SEPs indicated a common origin in the sensorimotor cortex. This observation provides further documentation of a cortical origin for some types of asterixis in humans. PMID- 1620138 TI - Severe generalised dystonia associated with a mosaic pattern of striatal gliosis. AB - A mosaic pattern of striatal pathology is described in a male who developed severe generalised dystonia from the age of 10 years, and died at the age of 18 years. There was no family history of dystonia, and extensive investigations during his life failed to identify a cause for the dystonia. The caudate nucleus and putamen showed a network of cell loss and gliosis surrounding islands of preserved striatum. Dorsal parts showed confluent gliosis, and ventral parts were spared. The pattern suggested a correlation with patch-matrix organisation, but there was no correlation with the distribution of calbindin immunoreactive cells, which are present in the matrix of the classical striosome-matrix organisation. The pathological findings were unlike those in status marmoratus, perinatal hypoxia-ischaemia, Huntington's disease, and neuroacanthocytosis, but similar to those reported in a 44-year-old man with predominantly cranial dystonia. PMID- 1620139 TI - Influence of cholinergic system on myoclonus in myoclonic epilepsies. AB - The effect of two drugs upon multifocal myoclonic jerks was evaluated. The drugs influence the central cholinergic system in opposite ways. Eight patients with progressive and nonprogressive myoclonic epilepsy were tested. The single blind test was used. The number of myoclonic jerks after intravenous physostigmine (mean dose 0.02 mg/kg) and that after atropine (0.04 mg/kg) was compared to number of myoclonic jerks in the drug-free periods and with placebo. Placebo was without an effect. Physostigmine slightly increased the number of jerks. Atropine decreased the number significantly. In most patients the results were not striking. It is suggested that the cholinergic system may participate in the physiopathology of the studied myoclonus in a rather indirect, perhaps modulating way. PMID- 1620140 TI - Effect of aging and dopaminomimetic therapy on mitochondrial respiratory function in Parkinson's disease. AB - Oxygen consumption and enzyme activity were evaluated in platelet mitochondria from 17 patients with Parkinson's disease. In comparison with age-matched controls, no consistent abnormality could be discerned in complex I, complex II III, or complex IV oxygen consumption, or in the enzyme activity of these respiratory chain complexes. Neither chronic therapy with levodopa/carbidopa alone nor in combination with deprenyl significantly affected any measure of mitochondrial respiratory function. There was no discernible relationship between patient age or disease severity and any parameter of mitochondrial respiration. Moreover, blood lactate levels following glucose loading were not different in patients and controls. These results fail to support the occurrence of a generalized defect in any mitochondrial respiratory function in Parkinson's disease. PMID- 1620141 TI - Impairment of high-contrast visual acuity in Parkinson's disease. AB - Several studies have shown that the visual system is affected in Parkinson's disease (PD) with reduced contrast sensitivity, low-contrast acuity, and flicker sensitivity, as well as altered electroretinograms (ERGs) and pattern visual evoked potentials (VEPs). Apparently, however, no study has yet specifically determined whether visual acuity to high-contrast stimuli is impaired in PD. Visual acuity was measured in a group of 16 patients with PD, both on and off drugs (for 24 h), and 16 age- and sex-matched normal control subjects. Acuity was impaired in the PD group both on standard Snellen chart and on a screen in a computerized test of visual resolution. The degree of impairment was 24 and 25%, respectively, in the two tests. The PD patients had marginally better acuity on both tests while receiving drugs, but the differences were not significant. The difference between the two groups was consistent with impaired resolution and could not be accounted for by any perceptual dysfunction that may also have been present in the PD group. Conversely, however, impaired acuity may be implicated in studies that have reported mild deficits of visuospatial/visuoperceptual function in PD. Reduced acuity appears to be a subtle sequela of dopaminergic deficiency in the visual system. PMID- 1620142 TI - Kinetic-dynamic relationship of oral levodopa: possible biphasic response after sequential doses in Parkinson's disease. AB - The potential difference in the concentration-effect relationship of oral sequential doses of levodopa was explored in six Parkinsonian patients with complex fluctuating response. These patients showed "wearing-off phenomena" characterized by a transient worsening of motor function at the end of the first morning dose response to below baseline values and complained of a progressive reduction of levodopa effect during the day. A first standard levodopa dose was given in the morning, after an overnight fast and levodopa withdrawal. A second equal levodopa dose was administered immediately at the end of the first dose deterioration phase. Postimprovement worsening of motor response was also observed after the second levodopa dose in all patients. No significant difference in the pharmacokinetics of levodopa or in duration or magnitude of motor response could be appreciated between the two doses. These results further support the suggestion that, under controlled dietary conditions, plasma levodopa levels and effects relationship is reproducible between doses. Moreover, even when transient deterioration of motor function occurs between levodopa doses, the central dopaminergic system appears to remain responsive to the drug. PMID- 1620143 TI - Intravenous boluses and continuous infusions of L-dopa methyl ester in fluctuating patients with Parkinson's disease. AB - In six patients with Parkinson's disease exhibiting severe "on-off" phenomena, a 200-mg intravenous bolus of either L-DOPA or of its methyl ester were equally effective in reversing motor deficits, although the duration of action of the methyl ester was shorter. There were no marked differences in pharmacokinetic parameters for L-DOPA plasma levels after administration of L-DOPA and the methyl ester. In three patients, optimal infusion rates for the maintenance of mobility were established for L-DOPA and L-DOPA methyl ester. Both drugs were able to maintain patients "on" throughout a 12-h infusion period. However, on average the optimal infusion rate of L-DOPA methyl ester was 2.7 times greater than that for L-DOPA. There was no marked difference in the plasma levels of L-DOPA achieved, but 3-O-methyl DOPA levels increased more after infusion of L-DOPA methyl ester than after infusion of L-DOPA itself. The half-life of elimination and volume of distribution of L-DOPA formed from the methyl ester were markedly increased compared with values obtained after either an intravenous bolus of methyl ester or after an intravenous infusion of L-DOPA itself. An intravenous bolus of L-DOPA methyl ester produces an equivalent magnitude of clinical response to the same dose of L-DOPA. However, higher optimal infusion rates of methyl ester than L DOPA are required to produce continuous effect. The pharmacokinetic handling of L DOPA methyl ester given by intravenous infusion may differ from that of L-DOPA when given by the same route. PMID- 1620144 TI - Voluntary stimulus-sensitive jerks and jumps mimicking myoclonus or pathological startle syndromes. AB - Five patients who presented with stimulus-induced jerking as part of an apparent myoclonic or pathological startle syndrome are reported. Neurophysiological observations in these patients suggested the jerks were voluntary in origin. These included (a) variable latencies to the onset of stimulus induced jerks, (b) latencies were greater than that seen in reflex myoclonus of cortical or brainstem origin, and were (c) longer than the fastest voluntary reaction times of normal subjects, (d) variable patterns of muscle recruitment within each jerk and, (e) significant habituation with repeated stimulation. It is argued that these features are consistent with a voluntary origin for the jerks and enable them to be distinguished from the stereotyped electrophysiological characteristics of myoclonus of cortical and brainstem origin. Electrophysiological recordings may help identify patients with this form of psychogenic movement disorder. PMID- 1620145 TI - Dystonia following head trauma: a report of nine patients and review of the literature. AB - We report nine patients who developed dystonia following head trauma. The most frequent form was hemidystonia only (six patients). One patient presented with hemidystonia plus torticollis, one with bilateral hemidystonia and one with torticollis only. Seven patients sustained a severe head injury, and two had a mild head injury. At the time of injury, six were younger than 10 years, two were adolescents, and the patient with torticollis only was an adult. Except in the patient with torticollis only, the onset of dystonia varied considerably from months to years. All patients with hemidystonia had posthemiplegic dystonia of delayed onset. Seven out of 8 patients with hemidystonia had lesions involving the contralateral caudate or putamen, as demonstrated by CT and MR. The patient with hemidystonia plus torticollis had no lesion to the basal ganglia, but a contralateral pontomesencephalic lesion. Response to medical treatment was generally poor. Functional stereotactic operations were performed in seven patients. A variety of factors may be responsible for the vascular or nonvascular posttraumatic basal ganglia lesions, which may lead to dystonia. The pathophysiology seems to be more complex than thought previously. We believe that dystonia following head injury is not as rare as is assumed. Awareness of its characteristics and optimized diagnostic procedures will lead to wider recognition of this entity. PMID- 1620146 TI - Postural axial tremor in a patient with cerebellar atrophy. AB - A patient affected by low-frequency postural tremor of the trunk and limbs is reported. Apart from mild dysarthria and gait ataxia, no other neurological abnormalities were present. Cerebellar atrophy was demonstrated by means of magnetic resonance imaging. The tremor was associated with alternating activity in antagonistic muscles; it was triggered whenever a contraction of lumbar back extensor muscles occurred. Electrical stimulation of the cerebellum did not produce the normal suppression phases of motor responses evoked by a magnetic stimulation of the cerebral cortex. PMID- 1620147 TI - "Rubral" tremor induced by a neuroleptic drug. AB - "Rubral" tremor is a rare movement disorder that occurs typically with midbrain damage. It is defined by its presence at rest, with sustained posture, and with movement. Whether it is a single-tremor disorder or a combination of two distinct tremors is debated. This report chronicles a severe neuroleptic induced "rubral" tremor in a patient who had had a stable posttraumatic ataxia. The dramatic response to benztropine and bromocriptine is illustrated in the videotape. PMID- 1620148 TI - Levodopa-induced diphasic dyskinesias improved by subcutaneous apomorphine. PMID- 1620150 TI - Induction of mania by apomorphine in a depressed parkinsonian patient. PMID- 1620149 TI - Temporary deterioration in parkinsonian signs after modest alcohol intake. PMID- 1620151 TI - [The role of histidine in regulating the synthesis of purine nucleotides in Escherichia coli cells]. AB - Coordination of GTP and 5-aminoimidazole-4-carboxamide riboside 5'-phosphate pools changes was studied. The CTP pool is an important component of Escherichia coli metabolism, while AICAR 5'-phosphate being one of alarmones controls the synthesis of GTP. Main attention was paid to histidine, the biosynthesis of which is connected with formation of purine nucleotides. The expression of the histidine operon and biosynthesis of histidine are shown to change the AICAR pool and help the formation of the GTP pool. The ribosomal antibiotics streptomycin and chloramphenicol may cause the temporary deficiency of GTP eliminated by the increase of alarmone AICAR pool. The latter event is concluded to cause the increase in GTP pool independent of the means of AICAR accumulation (C1 pholatedependent restriction of metabolization or, vice versa, the stimulation in the histidine biosynthesis pathway). PMID- 1620152 TI - [Study of phage BBL1 of Brevibacterium flavum and construction of a plasmid containing the cos-sequence of BBL1]. PMID- 1620153 TI - [Mutations in Francisella tularensis, decreasing the virulence of these bacteria and leading to a change in the immune response upon infection of experimental animals with them]. AB - The research was aimed at isolation of Francisella tularensis mutants possessing the decreased virulence for experimental animals and mediating the changes in the animal immune response. A number of spontaneous and induced mutants of the American and European subtypes of Francisella tularensis were selected for antibiotics resistance or detergent sensitivity. All the obtained mutants have the decreased virulence and differ in their ability to induce the protective antitularemia immunity or ability to induce the humoral immune response in the laboratory animals. The dimeric immunoprecipitation in gel as well as immunoblotting have shown the mutations decreasing the virulence to cause the loss by bacteria of a number of antigenic structures (in case the virulence is completely lost) or changes in antigenic structure resulting in inability of bacteria to induce the humoral immune response when immunizing the laboratory animals. The latter occurs in partially virulent mutants of the vaccine mutant type. The concomitant changes in virulence, ability to cause protective immunity or humoral immune response of the mutants is discussed. PMID- 1620154 TI - [DNA-protein interactions in chromatin particles differing in electrophoretic mobility]. AB - The chromatin particles from Ehrlich carcinoma differing in the electrophoretic mobility were divided to a transcription active (c-particles) and transcription inactive (a-particles) fractions. Analysis of the DNA-protein interaction strength by the nucleoprotein-celite-chromatography has demonstrated that the majority of DNA-protein relationships in the a-particles is destroyed at NaCl concentrations exceeding 2 M, while in the c-particles at 1 M of NaCl. The study of NPC-chromatographic position of DNA depending on the particle size has shown that in slightly fragmented by streptococcal nuclease preparations of chromatin the DNA-protein relationships are destroyed at 3 M and 1 M of NaCl. Nevertheless, the position of the DNA spike on the chromatogram is not definitely dependent on the particle size. PMID- 1620155 TI - Pyrimethamine resistant mutations in Plasmodium falciparum. AB - Three mutations in Plasmodium falciparum yielding increased resistance to pyrimethamine were obtained following treatment with chemical mutagens and selection in presence of pyrimethamine. From parasite clone TM4/8.2 a mutant, TM4/8.2/4.1, was produced which raised pyrimethamine resistance about 500 times and was found to involve an amino acid change in the DHFR-TS enzyme molecule from Ser108 to Asn108. A clone of another isolate, T9/94, yielded a mutant, T9/94/300.300, raising pyrimethamine resistance about 10 times and involving an amino acid change from Ile164 to Met164. However, another mutant from T9/94, T9/94/M1-1(b3), although it raised the pyrimethamine resistance 100 times, did not involve any changes in the coding sequence of the DHFR-TS gene, but resulted in the production of about twice as much DHFR-TS enzyme as the original clone T9/94. No amplification of the DHFR-TS gene was detected. It is concluded that changes in pyrimethamine resistance of malaria parasites may arise in at least 2 ways: (1) by structural changes in the DHFR domain of the DHFR-TS gene (as previously found by other workers); (2) by other changes, possibly affecting the expression of the DHFR-TS gene. The relative importance of these 2 mechanisms in causing resistance in wild populations of P. falciparum is discussed. PMID- 1620156 TI - Difference spectroscopic characterisation of the cytochrome complement in Acanthocheilonema viteae. AB - (Dithionite-reduced) minus (ferricyanide-oxidised) difference spectra of 600 x g and 12,000 x g subcellular pellet fractions of adult male Acanthocheilonema viteae exhibited alpha-absorption maxima (296 K) attributable to Cyt c555, Cyt b562 and aa3 (600-605 nm). The gamma(Soret) maximum of both fractions was evident at 427 nm, with a shoulder at 432-434 nm. 600 x g and 12,000 x g pellet fractions of adult female and mixed-sex adult A. viteae exhibited similar absorption maxima. (Succinate-reduced)--(ferricyanide-oxidised) difference spectra of the 12,000 x g pellet fraction of mixed-sex adult A. viteae showed absorption maxima at 555 and 562 nm, 600 and 630 nm, suggesting the reduction of Cyt c555, Cyt b562, Cyt aa3 (600 nm) and an unidentified species (630 nm peak) Antimycin A (10( 6) M) induced the disappearance of the maxima at 555, 600 and 630 nm corresponding to Cyt c555, Cyt aa3 and the unidentified species; the maximum at 562 nm prevailed in the presence of antimycin A. These antimycin A induced changes can be cited as classical evidence for the functional involvement of these a, b and c type cytochromes in respiratory electron transport. (Dithionite reduced + CO)--(dithionite reduced) difference spectra suggest that adult A. viteae may have one or more CO-binding-species, one of which appears to be a low spin-haemoprotein with a b-type or c-type haem, which has essentially an electron carrier function rather than a ligand binding function. PMID- 1620157 TI - Inhibitors of the major cysteinyl proteinase (GP57/51) impair host cell invasion and arrest the intracellular development of Trypanosoma cruzi in vitro. AB - Peptidyl diazomethane (PDAM) derivatives, a class of irreversible inhibitors for cysteine proteinase, were screened for the ability to impair Trypanosoma cruzi invasion and intracellular development in primary cultures of heart muscle cells (HMC). T. cruzi GP57/51, a purified cysteinyl proteinase, and the substrate Z-Phe Arg-NHMec were used to determine inhibition rate constants (k'+2) by continuous kinetic assays. The k'+2 values ranged from 25,400 to 2,800. The best inhibitors of GP57/51 had bulky hydrophobic residues in the P1 position (in addition to P2), the S1 sub-site specificity of the enzyme being thus similar to mammalian cathepsin L. The effects of these PDAM on parasite infectivity were then investigated. The ability to invade HMC was markedly impaired when trypomastigotes were briefly exposed to 10 microM of Z-(S-Bzl)Cys-Phe-CHN2. Striking effects were observed when PDAM were added to HMC cultures that had been previously infected with trypomastigotes: Z-(S-Bzl)Cys-Phe-CHN2 with an IC50 of 0.4 microM, and less markedly Z-Phe-Phe-CHN2 and Z-Tyr-Phe-CHN2 (or Z-Phe-Tyr CHN2) blocked amastigote replication as well as their transformation into trypomastigotes, thereby arresting intracellular development. Bz-Phe-Gly-CHN2, in contrast, failed to display antiparasite activity. Direct characterization of the target cysteinyl proteinase was sought, by incubating viable amastigotes or infected HMC with Z-[125I]Tyr-Phe-CHN2. Affinity labeling implicated GP57/51 as the major cysteinyl proteinase target for this probe. We propose that T. cruzi intracellular development is critically dependent on GP57/51 (cruzipain). Selective inhibitors for this cysteinyl proteinase may have therapeutic potential. PMID- 1620159 TI - Isolation and characterization of a cyclic nucleotide-independent protein kinase from Leishmania donovani. AB - We describe here a protein kinase from the promastigote form of the parasitic protozoan, Leishmania donovani, purified to near homogeneity to a single-subunit, 34-kDa protein. This enzyme does not require a cofactor, and has several characteristics in common with the catalytic subunit of mammalian cAMP-dependent protein kinase, for example, preference for kemptide as a substrate, phosphorylation of serine residues of protamine and inhibition by the mammalian heat-stable inhibitor. The leishmanial enzyme can associate with the regulatory subunit of mammalian cAMP-dependent protein kinase to form an inactive holoenzyme that is activated by cAMP and is protected from inhibition by thiol reagents. From these results it is concluded that L. donovani promastigotes possess a protein kinase which has similar characteristics with the mammalian catalytic subunit of cAMP-dependent protein kinase. PMID- 1620158 TI - p-Aminobenzoic acid transport by normal and Plasmodium falciparum-infected erythrocytes. AB - De novo folate biosynthesis is required for the growth of malarial parasites and is inhibited by several important antimalarial agents. We show here that exogenous p-aminobenzoic acid (pABA) can be utilized by malaria parasites to synthesize folates. The transport of pABA into parasite infected red cells was therefore characterized. Normal red cells transport pABA in a saturable and energy-dependent manner, with a dissociation constant of 83 nM. pABA transport in parasite-infected red cells may use the same mechanism, as demonstrated by similarities in time course, concentration-response, and dissociation constant (111 nM). The transport capacity of red cells is temperature-, energy- and pH dependent. It is inhibited by the proton ionophore, carbonylcyanide m chlorophenylhydrazone (CCCP), but not by the sodium ionophores nigericin and monensin. p-Aminosalicylic acid (PAS) inhibits pABA transport competitively, with a inhibition constant of 378 nM. Phloritin, flufanamic acid, and 4,4' diisothiocyanatostilbene-2,2'-disulfonic acid (DITS), which are inhibitors of the anion transporter (band 3), and oxalic acid, a substrate of this transporter, partially inhibit pABA transport into both normal and infected red cells. Interestingly, in both normal and infected red cells, the inhibitory effects of PAS and the anion transport inhibitors are additive, suggesting the involvement of 2 independent mechanisms. PMID- 1620160 TI - Transcribing and replicating particles in a double-stranded RNA virus from Leishmania. AB - During the replicative cycle of many double-stranded RNA viruses, transcription of particles with a double-stranded RNA genome alternates with replication of particles containing a single-stranded genome. In virions infecting some strains of Leishmania guyanensis the putative transcriptase and replicase activities of the RNA-dependent RNA polymerase were previously detected in vitro. Northern hybridization to RNA of known polarity demonstrates that the single-stranded RNA products are of positive polarity and, by definition, are the products of the viral transcriptase. Re-evaluation of previously published data in the light of these findings suggests that transcription in Leishmania viruses is conservative. Sedimentation in sucrose gradients revealed two types of viral particles; single stranded RNA particles comprised a small fraction of the virus population and sedimented more slowly than the peak of double-stranded RNA particles. In agreement with the replicative model of other dsRNA viruses, these single stranded particles co-purified with the viral replicase activity that resulted in double-stranded RNA synthesis. In virus-infected promastigote extracts replicase activity decreased with increasing parasite density in culture, suggesting a correlation between cell division and viral replication. PMID- 1620161 TI - Synthesis and secretion of proteins by released malarial parasites. AB - Controlled mechanical homogenization of Plasmodium falciparum-infected erythrocytes releases parasites of a quality sufficient for studying the export of newly synthesized plasmodial proteins. Protein synthesis occurs within intact released parasites as defined by resistance of acid-insoluble incorporation of radiolabel to high levels of exogenously added EDTA, hexokinase, and RNaseA. While exogenously added ATP and erythrocyte cytosol were not essential for biosynthetic activity at levels comparable to that seen in infected erythrocytes, the addition of an extracellular ATP regenerating system (ARS) stimulated the synthesis of parasite proteins. Conversely, parasite viability and biosynthetic activity are decreased by the addition of a non-hydrolyzable ATP analogue (ATP gamma S), ADP, or ATP in the absence of a regenerating system. These data suggest a metabolic interdependence between extracellular energy metabolism and biosynthetic functions within the parasite. The export of a predominant subset of proteins was retarded in the presence of Brefeldin A, indicating the existence of a classical secretory pathway characteristic of that seen in higher eukaryotic cells. Interestingly, a Brefeldin A-insensitive component of export was also consistently observed; this may suggest the existence of an additional alternative secretory mechanism in malaria. PMID- 1620162 TI - Genes selectively expressed in the infectious (metacyclic) stage of Leishmania major promastigotes encode a potential basic-zipper structural motif. AB - Complementary DNA clones representing transcripts selectively expressed in the non-dividing, infective (metacyclic) stage of Leishmania major promastigotes (MP) were identified by differential and subtractive screening. The majority of the selected clones hybridized on Northern blots to a set of transcripts highly expressed by MP, but to a much lower extent in proliferating and stationary-phase attenuated promastigotes. Stationary, but not log-phase cultures, of each of 5 L. major strains showing a potential for differentiation to metacyclics, expressed these transcripts (MAT-1; MP-associated transcripts). From sequence analysis of full-length cDNA clones corresponding to the predominating MAT-1 species, an open reading frame encoding a 139 aa polypeptide (15.4 kDa) was predicted and supported by immunoprecipitation by kala-azar sera of reticulocyte extract translation products using in vitro transcribed RNA. Although no significant primary sequence homology to database nucleic acid and protein sequences was found, the sequence displays similarities to the basic-zipper families of transcription regulatory proteins. PMID- 1620163 TI - Calcium homeostasis in Trypanosoma cruzi amastigotes: presence of inositol phosphates and lack of an inositol 1,4,5-trisphosphate-sensitive calcium pool. AB - The permeabilization of Trypanosoma cruzi amastigotes with digitonin allowed the study of Ca2+ fluxes between intracellular organelles in situ. In addition, fura 2 was used to determine the cytosolic Ca2+ concentration in the intact cells. When amastigotes were permeabilized in a reaction medium containing MgATP, succinate and 3.5 microM Ca2+, they lowered the medium Ca2+ concentration to the submicromolar level, a range which correlates favorably with that detected in the intact cells with fura-2. The presence of 1 microM FCCP strongly decreased the initial rate of Ca2+ sequestration by these permeabilized cells. This FCCP insensitive Ca2+ uptake, probably represented by the endoplasmic reticulum, was completely inhibited by 500 microM vanadate. On the other hand, when vanadate instead of FCCP was present, the initial rate of Ca2+ accumulation was decreased and the Ca2+ set point was increased to about 0.8 microM. The succinate dependence and FCCP sensitivity of the later Ca2+ uptake indicate that it may be exerted by the mitochondria. Despite the presence of inositol phosphates, as determined by [3H]inositol incorporation, and of a large extramitochondrial Ca2+ pool, no IP3-sensitive or thapsigargin-sensitive Ca2+ release could be detected in either amastigotes or epimastigotes. PMID- 1620164 TI - The GMP reductase gene of the nematode Ascaris lumbricoides var. suum. PMID- 1620165 TI - Molecular cloning of a 16-kilodalton Cu/Zn superoxide dismutase from Schistosoma mansoni. PMID- 1620167 TI - Isolation of skeleton-associated knobs from human red blood cells infected with malaria parasite Plasmodium falciparum. PMID- 1620166 TI - Comparison of the carboxy-terminal, cysteine-rich domain of the merozoite surface protein-1 from several strains of Plasmodium yoelii. PMID- 1620168 TI - Characterization of a possible tRNA synthetase gene from Onchocerca volvulus. PMID- 1620169 TI - Treatment of preterm labor with the beta-adrenergic agonist ritodrine. AB - BACKGROUND: Beta-adrenergic agonists are commonly used to arrest premature labor. Although treatment of preterm labor with these agents can delay delivery by 24 to 48 hours, the potential risks and benefits to the mother and infant before and after delivery have not been adequately assessed. METHODS: We randomly assigned 708 women with preterm labor at six hospitals to receive an intravenous infusion of either the beta-adrenergic agonist ritodrine (n = 352) or placebo (n = 356). Assignment was made with stratification according to four categories of gestational age (20 to 23 weeks, 24 to 27 weeks, 28 to 31 weeks, and 32 to 35 weeks). The primary objective was to assess the effect of ritodrine on perinatal mortality. Secondary objectives were the evaluation of the causes of perinatal death, the extent to which delivery was delayed with ritodrine, and the effects on birth weight, maternal morbidity, neonatal morbidity, and infant morbidity at 18 months of postnatal age, corrected for preterm delivery. RESULTS: Among the 771 infants born to the women in the study (including 63 pairs of twins), there were 23 deaths (6.1 percent) in the ritodrine group and 25 deaths (6.4 percent) in the placebo group (event-rate difference, -0.3 percent; 95 percent confidence interval, -3.7 percent to 3.1 percent). There was no difference between the groups in the extent of delay of delivery, the incidence of delivery before 37 weeks' gestation, the proportion of babies weighing less than 2500 g, or measures of neonatal morbidity. Maternal morbidity (such as chest pain and cardiac arrhythmias) occurred more frequently but not exclusively in the ritodrine group. One infant born to a woman in the ritodrine group and five infants born to women in the placebo group had cerebral palsy (P = 0.09). There was a slight but not significant trend toward an improved score on the Bayley Psychomotor Development Index at 18 months of age among the infants of the ritodrine-treated women. CONCLUSIONS: We found that the use of ritodrine in the treatment of preterm labor had no significant beneficial effect on perinatal mortality, the frequency of prolongation of pregnancy to term, or birth weight. PMID- 1620170 TI - Treatment of supraventricular tachycardia due to atrioventricular nodal reentry by radiofrequency catheter ablation of slow-pathway conduction. AB - BACKGROUND: Atrioventricular nodal reentrant tachycardia (AVNRT), the most common form of supraventricular tachycardia, results from conduction through a reentrant circuit comprising fast and slow atrioventricular nodal pathways. Antiarrhythmic drug therapy is not consistently successful in controlling this rhythm disturbance. Catheter ablation of the fast pathway with radiofrequency current eliminates AVNRT, but it can produce heart block. We hypothesized that catheter ablation of the site of insertion of the slow pathway into the atrium would eliminate AVNRT while leaving normal (fast-pathway) atrioventricular nodal conduction intact. METHODS AND RESULTS: Eighty patients with symptomatic AVNRT were studied. Retrograde slow-pathway conduction (in which the earliest retrograde atrial potential was recorded at the posterior septum, close to the coronary sinus) was present in 33 patients. The retrograde atrial potential was preceded by a potential consistent with activation of the atrial end of the slow pathway (ASP). In 46 of the 47 patients without retrograde slow-pathway conduction, a potential with the same characteristics as the ASP potential was recorded during sinus rhythm. Radiofrequency current delivered through a catheter to the ASP site (in the posteroseptal right atrium or coronary sinus) abolished or modified slow-pathway conduction in 78 patients, eliminating AVNRT without affecting normal atrioventricular nodal conduction. In the single patient without ASP, the application of radiofrequency current to the proximal coronary sinus ablated the fast pathway and AVNRT: Atrioventricular block occurred in one patient (1.3 percent) with left bundle-branch block, after inadvertent ablation of the right bundle branch. AVNRT has not recurred in any patient during a mean (+/- SD) follow-up of 15.5 +/- 11.3 months. Electrophysiologic study 4.3 +/- 3.3 months after ablation in 32 patients demonstrated normal atrioventricular nodal conduction without AVNRT: CONCLUSIONS: Catheter ablation of the atrial end of the slow pathway using radiofrequency current, guided by ASP potentials, can eliminate AVNRT with very little risk of atrioventricular block. PMID- 1620171 TI - Breast cancer (1) PMID- 1620172 TI - Metabolic disturbances and wasting in the acquired immunodeficiency syndrome. PMID- 1620173 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 31-1992. A 68-year-old man with acute mitral regurgitation. PMID- 1620175 TI - Pharmaceutical promotions--a free lunch? PMID- 1620174 TI - Is insulin-dependent diabetes mellitus environmentally induced? PMID- 1620176 TI - The active management of labor. PMID- 1620177 TI - The active management of labor. PMID- 1620178 TI - The active management of labor. PMID- 1620179 TI - Early versus late treatment with zidovudine. PMID- 1620180 TI - Early versus late treatment with zidovudine. PMID- 1620181 TI - Clinical problem-solving: how sure is sure enough? PMID- 1620182 TI - Clinical problem-solving: how sure is sure enough? PMID- 1620183 TI - Clinical problem-solving: how sure is sure enough? PMID- 1620184 TI - Use of phentolamine for cocaine-induced myocardial ischemia. PMID- 1620185 TI - Selective decontamination of the digestive tract. PMID- 1620186 TI - Selective decontamination of the digestive tract. PMID- 1620187 TI - Fecal incontinence. PMID- 1620188 TI - Education or promotion? PMID- 1620189 TI - Methodological issues in prevention research on drug use and pregnancy. PMID- 1620190 TI - Methodological issues in epidemiological, prevention, and treatment research on drug-exposed women and their children. Technical review meeting. Baltimore, Maryland, July 25-26, 1990. PMID- 1620191 TI - Who is it going to be? Subject selection issues in prenatal drug exposure research. PMID- 1620192 TI - Subject recruitment and retention for longitudinal research: practical considerations for a nonintervention model. PMID- 1620193 TI - Subject recruitment and retention issues in longitudinal research involving substance-abusing families: a clinical services context. PMID- 1620194 TI - Perinatal substance abuse and AIDS: subject selection, recruitment, and retention. AB - Studies that involve subjects who are HIV infected as well as chemically dependent present special challenges to the study team. HIV infection is now so common in many parts of the country and infection can potentially influence so many commonly used endpoints for perinatal chemical dependence studies that HIV must be considered in these studies. Some of the factors that need to be taken into account in the design of studies include the staging of HIV illness, the consequences of HIV-induced CNS disease, the effects of HIV treatment, and the biases in subject selection that arise due to inaccurate information about risk factors and imbalance in sources of subjects and controls. In addition, the study team needs to remember the community and staff fear and bias that are often encountered in the care of HIV-infected patients. Fruitful sources of subjects for perinatal studies include prenatal clinics and delivery rooms, chemical dependence programs, and the network of community social agencies. Retention of this challenging group is strongly aided by the establishment of a seamless system of services that includes all aspects of general medical care, HIV specialty care, access to treatment protocols, and psychosocial care. PMID- 1620195 TI - Measurement issues in the evaluation of experimental treatment interventions. AB - The final discussion of followup measurement highlights earlier discussions of patient and treatment measurement. Followup is the best assessment of the efficacy of a treatment intervention. Therefore, it is critical to have a clear set of baseline measures on the patient in those areas that are expected to be able to improve with the intervention and to repeat these measures at followup to assess improvement and outcome. The measures that are collected at followup are essentially identical to the measures that were collected at the time of treatment admission but in abbreviated form. However, the same methodological issues, techniques, and considerations apply. As at the time of the initial assessment, the patient should be measured in all those areas that are expected to be changed, the patient should be assessed with multiple methods (interview questionnaire and objective laboratory data), and all care should be taken to assure the patient that the information will be treated in a professional manner and that her privacy and confidentiality will be protected. An effective posttreatment evaluation requires effective tracking, locating, and reinterviewing each patient following treatment. The ability to recontact these patients after treatment is almost entirely dependent on the level of information, patient preparation, and interagency cooperation established during the time the patient was in treatment. Followup is an important but difficult job that must be coordinated from the very start of treatment and must involve the patient, followup staff, clinical program, and sponsoring agency or agencies. PMID- 1620196 TI - Discussion: subject selection, recruitment, and retention in longitudinal studies involving perinatal substance abuse and human immunodeficiency virus infection. PMID- 1620197 TI - Measures of pregnant, drug-abusing women for treatment research. PMID- 1620198 TI - Assessing acute and long-term physical effects of in utero drug exposure on the perinate, infant, and child. PMID- 1620199 TI - Methodological issues in the assessment of the mother-child interactions of substance-abusing women and their children. PMID- 1620200 TI - Discussion: measurement issues in the study of effects of substance abuse in pregnancy. PMID- 1620201 TI - Studies of prenatal drug exposure and environmental research issues: the benefits of integrating research within a treatment program. PMID- 1620202 TI - How the environment affects research on prenatal drug exposure: the laboratory and the community. AB - This has been a brief overview of some of the many ways in which the environment in which prenatal drug research is carried out affects the process of research and its outcome. In many ways, this chapter is a review of factors that many people know about but rarely discuss in public. Most scholarly articles present research in this area as though it is a smooth and orderly process not much troubled by environmental constraints. The extent to which research flaws are criticized, even those that are inevitable to the process, discourages frank discussion of these problems that are familiar to most investigators who attempt to conduct clinical research in difficult areas. The purpose of this chapter is to make some of these issues more explicit so that they can be planned for in future work and taken into account when current work is reviewed. PMID- 1620203 TI - Discussion: research environment and use of multicenter studies in perinatal substance abuse research. PMID- 1620204 TI - Discussion: statistical analysis in treatment and prevention program evaluation. PMID- 1620205 TI - Process measures in interventions for drug-abusing women: from coping to competence. AB - As a guide to the selection of process and outcome measurement in interventions with drug-abusing women, we have offered a model of fundamental coping processes. Three coping processes--reinforcer management, challenge management, and affect management--appear critical to women's competence and physical hardiness. When these processes go awry, substance abuse is a likely result. For successful recovery from substance abuse, good fortune or purposeful intervention must promote these coping processes. To measure the impact of any intervention with drug-abusing women, methods of assessing fundamental coping processes during intervention (process measures) and repeatedly after intervention (outcome measures) are needed. We have described multiple methods of measuring fundamental coping processes from diverse vantage points: self-report, behavioral observation, biochemistry, and physiology. We have discussed how these measures relate to the theoretical model. Finally, we have indicated measures favored and used in our longitudinal and intervention research on adolescent and perinatal substance abuse. The final set of measures, as summarized in the list of recommended process and outcome measures on pages 324-325, is somewhat lengthy because the process of intervention is complex. Given the financial and structural limitations of research in drug treatment settings, it may not be possible for a single investigator to employ all the recommended measures. An adequate research design would employ two measures from each of the domains outlined. If resources allow, more extensive measurement procedures would be possible. PMID- 1620206 TI - Discussion: dilemmas in research in perinatal addiction--intervention issues. PMID- 1620207 TI - Alcohol- and drug-dependent pregnant women: laws and public policies that promote and inhibit research and the delivery of services. PMID- 1620208 TI - Mandatory reporting of child abuse and research on the effects of prenatal drug exposure. PMID- 1620209 TI - Discussion: effect of legal stipulations on the conduct of treatment and prevention research. PMID- 1620210 TI - Role of biologic markers in epidemiologic studies of prenatal drug exposure: issues in study design. PMID- 1620211 TI - Detection of prenatal drug exposure in the pregnant woman and her newborn infant. PMID- 1620212 TI - Methodological issues in obtaining and managing substance abuse information from prenatal patients. PMID- 1620213 TI - Discussion: caveats in testing for drugs of abuse. AB - Four mass screening techniques for drugs of abuse (TLC, RIA, EMIT, and FPI) have been described. For small-scale screening, TLC is the most cost-effective. Although it cannot achieve the sensitivity of the other three immunologically based techniques, TLC is sufficient for many purposes. All screening techniques are subject to interferences that can generate false-negatives or false positives. These results must be taken into account in analysis of the research data. In applying technology in new areas of research, one has to be aware of the basis and limits of that technology. Testing of drugs of abuse in urine is a well known technology in which most of the problems have been discovered. This technology is less proven for other media, such as hair, saliva, or meconium, leaving potential pitfalls for the unwary researcher. PMID- 1620214 TI - Drug abuse treatment in prison and jails. Technical review meeting. Rockville, Maryland, May 24-25, 1990. PMID- 1620215 TI - The challenge of drug abuse treatment in prisons and jails. PMID- 1620216 TI - Comprehensive system development in corrections for drug-abusing offenders: the Wisconsin Department of Corrections. PMID- 1620217 TI - Outcome evaluation of a prison therapeutic community for substance abuse treatment. PMID- 1620219 TI - Management of the drug-abusing offender. PMID- 1620218 TI - Evaluation of in-jail methadone maintenance: preliminary results. PMID- 1620220 TI - A coordinated approach for drug-abusing offenders: TASC and parole. PMID- 1620221 TI - Methodological issues: drug abuse treatment research in prisons and jails. PMID- 1620222 TI - Evaluation of the Federal Bureau of Prisons' drug treatment programs. PMID- 1620223 TI - Directions for practice and research. PMID- 1620224 TI - Program models. PMID- 1620225 TI - Drug treatment services in jails. PMID- 1620226 TI - HIV-1 infection in the correctional setting. AB - The correctional setting provides an opportunity to serve IV drug users who might otherwise be difficult to access. Interventions--including education, counseling, treatment for HIV-1 infection, and treatment for drug abuse--conducted in the correctional setting could have benefits for individual inmates and the surrounding community. PMID- 1620227 TI - Drug abuse treatment programs in the Federal Bureau of Prisons: initiatives for the 1990s. AB - Developing high-quality treatment programs is a foreboding challenge in any setting, particularly within a correctional setting. The groundwork has been established for one of the most comprehensive, longitudinal evaluations ever conducted with correctional populations regarding the effectiveness of professionally managed treatment programs. The long-term outcome evaluations should provide information regarding the effectiveness of a multitiered intervention strategy within the correctional setting. This kind of evaluation is reflected in the proposal for the evaluation of the BOP Drug Abuse Treatment Programs, submitted to NIDA (Federal Bureau of Prisons 1990). In the months and years ahead the study is expected to yield important information that will advance knowledge of substance abuse treatment. PMID- 1620228 TI - Correctional drug abuse treatment in the United States: an overview. PMID- 1620229 TI - Amity righturn: a demonstration drug abuse treatment program for inmates and parolees. PMID- 1620230 TI - Substance abuse services in juvenile justice: the Washington experience. PMID- 1620231 TI - Effects of 5-HT4 receptor stimulation on basal and electrically evoked release of acetylcholine from guinea-pig myenteric plexus. AB - The effects of 5-methoxytryptamine and 5-hydroxytryptamine (5-HT) on both basal and electrically evoked outflow of tritium were studied in guinea-pig myenteric plexus preparations preincubated with [3H]-choline. Basal outflow. 5 Methoxytryptamine caused a transient and calcium-dependent increase in basal outflow of [3H]acetylcholine that was abolished by tetrodotoxin. Ondansetron (1 mumol/l) did not affect the stimulatory response of 5-methoxytryptamine but ICS 205-930 (1 and 3 mumol/l) produced parallel rightward displacements of the concentration-response curve to 5-methoxytryptamine. The pKB value for ICS 205 930 was 6.6 suggesting an involvement of 5-HT4 receptors. 5-HT caused an increase in basal outflow of [3H]acetylcholine and a biphasic concentration-response curve was obtained. The maximal response of the first phase to 5-HT (release of 0.98% of tissue tritium) and the maximal response to 5-methoxytryptamine (0.94% of tissue tritium) were similar but 5-methoxytryptamine (-log EC50: 6.9) was less potent than 5-HT (-log EC50 of the high affinity component: 7.9). ICS 205-930 (0.01-1.0 mumol/l) acted as a competitive antagonist against the low affinity component of the 5-HT concentration-response curve with a pA2 value of 8.0. It is concluded that stimulation of both 5-HT4 receptors (by 5-methoxytryptamine and submicromolar concentrations of 5-HT) and 5-HT3 receptors (by micromolar concentrations of 5-HT) causes a release of acetylcholine which in turn leads to smooth muscle contraction. Electrically evoked outflow. This outflow of [3H] acetylcholine was concentration-dependently inhibited by both 5-methoxytryptamine and 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620232 TI - Effect of tianeptine on the central cholinergic system: involvement of serotonin. AB - The effect of tianeptine on in vivo acetylcholine (ACh) release from brain hemispheric regions of freely moving rats was investigated using the microdialysis technique coupled with a sensitive radioenzymatic method. Tianeptine, at the dose of 30 mg/kg i.p., reduced ACh release from dorsal hippocampi by 40% in 40 min, and induced a 30% decrease of ACh output from frontal cortices while at the doses of 10 and 20 mg/kg it had no effect. In striata the drug did not significantly affect ACh release although it showed a tendency to increase it. The ACh content in the three areas considered was not affected by tianeptine at above doses. The drug did not alter choline-o acetyltransferase and acetylcholinesterase activities suggesting that it did not influence the cholinergic system through direct action on the ACh metabolism; furthermore, it did not influence the sodium-dependent high-affinity uptake of choline in striatum, cortex and hippocampus. Impairment of serotonergic (5-HT) neurotransmission by chemical lesion of the median raphe nucleus or by metergoline, a blocker of 5-HT receptors, antagonized the cholinergic effect of tianeptine. The involvement of the serotonergic system is specific because lesions of the noradrenergic dorsal bundle failed to prevent the inhibitory action of tianeptine. The present data suggest that 5-HT may mediate the effect of tianeptine on the cholinergic system in dorsal hippocampi. PMID- 1620233 TI - SDZ ENS 163 is a selective M1 agonist and induces release of acetylcholine. AB - In the present study some pharmacological properties of the new muscarinic agonist SDZ ENS 163; (+)-(3S,cis)-3-ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl) methyl-2(3H)-thiophenonedihydrogenphosphate] have been investigated. In the rat superior cervical ganglion, a model for M1 muscarinic receptors, SDZ ENS 163 induced concentration-dependent depolarizations (pD2 = 6.5 +/- 0.3; efficacy = 128 +/- 4.2% compared to carbachol). SDZ ENS 163 was a very weak partial agonist with respect to M2 receptor-induced decrease in contractile force in rat left atria (efficacy = 14 +/- 2.9%). In addition, SDZ ENS 163 competitively antagonized the effect of carbachol in rat left atria (pA2 = 5.8 +/- 0.2). In the guinea-pig ileum SDZ ENS 163 was a partial agonist with respect to force of contraction mediated by M3 receptors (pD2 = 5.3 +/- 0.1; efficacy = 72 +/- 4.2%). The oxotremorine-induced inhibition of the electrically stimulated release of acetylcholine (ACh) in rat hippocampal slices was reversed by SDZ ENS 163 (pA2 = 5.5 +/- 0.1). In addition after oral administration SDZ ENS 163 (3-10 mumol/kg) reduced brain ACh levels, which is indicative of increased ACh turnover. Finally, increases in energy of the low frequency band (2-5 Hz) were observed in rat hippocampal EEG after intraperitoneal administration of SDZ ENS 163 (0.3-30 mumol/kg). We conclude that SDZ ENS 163 is a selective M1 agonist in vitro with an additional M2 antagonistic effect. The in vivo effects of SDZ ENS 163 may result both from postsynaptic M1 agonistic as well as M2 receptor antagonistic activity. The unique pharmacological profile of SDZ ENS 163 may prove clinically favourable for treatment of cognitive deficits. PMID- 1620234 TI - Carbachol potentiates isoprenaline-induced mucin secretion by rat submandibular gland. AB - We studied the effects of carbachol on isoprenaline-induced secretion of 3[H]glucosamine-labeled high molecular weight protein from in vitro fragments of rat submandibular gland. The concentration-response curve for isoprenaline was determined alone and in the presence of one of two concentrations of carbachol. Isobolic interaction indices were calculated from the resulting curves. The role of extracellular calcium on this interaction was assessed by examining the effect of increasing concentrations of [Ca2+]e on secretion induced by a fixed concentration of isoprenaline alone and in the presence of carbachol. Carbachol alone caused a small, but statistically significant, protein secretion. Carbachol markedly shifted the isoprenaline concentration-response curve to the left in a dose-dependent manner. In the absence of extracellular calcium, carbachol did not increase isoprenaline-induced secretion, but secretion increased as the [Ca2+]e was increased. The carbachol-induced increase in secretion reached a maximal level at approximately 2.0 mM [Ca2+]e. We conclude that carbachol's increase of isoprenaline-induced secretion of 3[H]glucosamine-labeled high molecular weight protein is not additive, but is true potentiation. This potentiation requires extracellular calcium, and may be maximal at physiological [Ca2+]e. PMID- 1620235 TI - Radiolabeling of dopamine uptake sites in mouse striatum: comparison of binding sites for cocaine, mazindol, and GBR 12935. AB - This study addressed the possibility of a unique binding interaction between cocaine and the dopamine transporter as compared with other blockers of dopamine uptake. Cocaine binding sites in a fresh P2 fraction of mouse striatum were labeled with [3H]CFT, a phenyltropane analog of cocaine also known as WIN 35,428, and compared with sites labeled with [3H]mazindol or [3H]GBR 12935. Under the conditions used, homogeneous binding was observed that was inhibited monophasically by cocaine, CFT, and mazindol; the same potencies were observed with the three radioligands. Saturation analysis in the presence and in the absence of unlabeled inhibitor (CFT, mazindol, cocaine) indicated a change in the Kd but not the Bmax, consonant with a competitive mechanisms. Tris-HCl reduced the affinity of each radioligand and unlabeled inhibitor without changing the Bmax. N-Ethylmaleimide reduced the binding of all radioligands equally and cocaine offered protection. The dissociation rate of [3H]CFT and [3H]mazindol binding was not affected by the presence of mazindol and CFT, respectively. The Bmax of [3H]CFT and [3H]mazindol binding was the same; the relatively higher value for [3H]GBR 12935 binding in analyses involving varying tritiated GBR 12935 only, was due primarily to an underestimation of the specific activity of [3H]GBR 12935. All results are in agreement with a one-site model in which cocaine, CFT, mazindol, and GBR 12935 share a common binding site in mouse striatum. PMID- 1620236 TI - Different and common intracellular calcium-stores mobilized by noradrenaline and caffeine in vascular smooth muscle. AB - Noradrenaline (NA) 1 microM and caffeine (CAF) 10 mM induce a contractile response in isolated rat aorta maintained at 37 degrees C either in the presence or absence of extracellular calcium. In Ca-free media the contractile response was reduced and contractile activity of CAF only occurred at 25 degrees C. NA induced a biphasic response in Ca-free medium, with a fast phasic contraction followed by a smaller more sustained contraction. The response induced by CAF consisted of a fast transient contraction which returned to a level below the resting tone. After washing, further addition of NA or CAF evoked no increase in smooth muscle tension. The influence of Mg-depletion in the extracellular medium on the contractile responses induced by NA and CAF in Ca-free medium was determined: similar response to NA or CAF in media with or without Mg after 2 min loading were observed, but after 15 min loading in Mg, Ca-free solution, the responses to NA or CAF were significantly higher than after incubation in Ca-free medium containing Mg. Differences were observed when contractile response to NA was elicited after the refilling process by loading the aortic strip in Ca containing Mg-free solution. In this case, instead of recovering the magnitude of contraction there was a significant decrease. The existence of two independent intracellular Ca-pools releasable by NA, one of them also sensitive to CAF, is postulated. The refill of the Ca-store specific to NA is dependent on the presence of Mg in the extracellular medium. In contrast, the refill of the common Ca-pool releasable by NA and CAF is independent of the extracellular Mg, but its spontaneous emptying is temperature-, and Mg-dependent. This suggests the intermediacy of an enzymatic process to extrude the Ca-content of this store to the extracellular space. PMID- 1620237 TI - Difference between aortic and renal vascular reactivity in cyclosporin A treated rats and the effect of cicletanine. AB - 4 Groups of 2 month-old male Wistar rats were treated with a) cyclosporin A (CyA) 30 mg/kg/day alone, b) CyA plus cicletanine (Cic) 60 mg/kg/day, c) vehicle (vegetable oil) 1 ml/100 g rat/day and d) no treatment for 8 weeks. The reactivity of isolated papillary muscle to isoprenaline and Ca2+ was not altered in any of the treated groups. Endothelium-dependent relaxation induced by acetylcholine was inhibited in aorta ring segments from CyA-treated rats as compared to that of control and CyA + Cic-treated rats. The relaxation induced by acetylcholine in rat aortas was similar in all groups in the presence of 10 microM indomethacin. Noradrenaline sensitivity of aortic segments was not affected by any treatments applied. The Ca(2+)-concentration response curves of aorta segments from CyA-treated and CyA + Cic-treated rats were shifted to the right as compared to control rats. In interlobar renal arteries the endothelium dependent relaxation induced by acetylcholine was not affected by any form of treatment. In renal arteries 10 microM indomethacin increased the maximal relaxation induced by acetylcholine about 50%. In these vessels noradrenaline sensitivity in CyA and CyA + Cic treated rats was higher than in controls. Cocaine, 3 microM, shifted the noradrenaline concentration response curve to the left about 0.4 log units in all renal vessel groups, thus renal vascular smooth muscle sensitivity to noradrenaline was significantly greater in vessels from rats receiving CyA than in vessels from control rats. Administration of CyA induced only slight renal morphological changes. Cic was without effect on CyA induced morphological abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620238 TI - Characterization of nicotinic acetylcholine receptors on cultured bovine adrenal chromaffin cells using modified L-[3H]nicotine binding assay. AB - To characterize the properties of nicotinic acetylcholine receptors (nAChRs) in autonomic ganglia, we examined L-[3H]nicotine binding to membrane fraction prepared from cultured bovine adrenal chromaffin cells, using a modified filtration method. Binding of L-[3H]nicotine to non-treated glass fiber filters interfered with the detection of specific binding to the membrane fraction. Presoaking glass fiber filters in 3% or higher concentrations of polyethyleneimine (PEI) solution (sixty times higher than earlier used concentration) for at least 5 h could reduce the binding of L-[3H]nicotine to the filters to the background level. Specific L-[3H]nicotine binding to the membrane fraction was detected only when the membrane fraction was prepared in Ca(2+)-and Mg2+ (EDTA, EGTA and protease inhibitors were added) -free buffer. Specific binding of L-[3H]nicotine was saturable and reversible. Both computer program and Scatchard analysis revealed a single class of high affinity binding sites with an average Kd of 8.9 nM and a Bmax of 42.5 fmol/mg protein. The Hill coefficient was 0.98. In inhibition studies, both cholinergic agonists (carbachol and L-nicotine) and ganglionic agonists (lobeline and 1,1-dimethyl-4-phenylpiperazinium iodide) were much effective in inhibiting L-[3H]nicotine binding, whereas both neuromuscular blocking (alpha-bungarotoxin and d-tubocurarine) and ganglionic blocking agents were less effective. These results suggest that high affinity nicotinic binding sites on adrenal chromaffin cells are nAChRs of the ganglion type, which have properties different from nAChRs on the neuromuscular junction but similar to nAChRs in the brain. PMID- 1620239 TI - NPY and carbachol raise Ca2+ in SK-N-MC cells by three different mechanisms. Evidence for inositol phosphate-independent Ca2+ mobilization by NPY. AB - We have compared the mechanism of NPY- and carbachol-stimulated Ca2+ increases in SK-N-MC cells. NPY stimulated Ca2+ mobilization via a pertussis toxin-sensitive mechanism. Carbachol stimulated Ca2+ mobilization and influx via pertussis toxin insensitive and -sensitive mechanisms, respectively. Carbachol but not NPY stimulated inositol phosphate accumulation by a pertussis toxin-insensitive mechanism. We conclude that carbachol promotes Ca2+ influx via a pertussis toxin sensitive G protein and Ca2+ mobilization via a pertussis toxin-insensitive G protein coupling to inositol phosphate generation; NPY stimulates Ca2+ mobilization via a pertussis toxin-sensitive G protein without apparent involvement of inositol phosphates. PMID- 1620240 TI - The action of (+/-)L-660,863 [(+/-)3-(3-amino-1,2,4-oxadiazole-5-yl) quinuclidine] at muscarinic receptor subtypes in vitro. AB - 1. The muscarinic pharmacology of a novel oxadiazole muscarinic agonist, (+/-) L 660,863, [+/-3-(3-amino-1,2,4-oxadiazole-5-yl)-quinuclidine] has been studied using pharmacological, radioligand binding and biochemical techniques, in vitro. 2. In isolated tissue experiments, (+/-)L-660,863 was a more potent agonist than carbachol in all preparations studied, being most potent at muscarinic receptors mediating negative chronotropy in guinea-pig right, spontaneously beating atria and least potent at receptors mediating contractions in canine saphenous vein and endothelial denuded rabbit aorta (-log EC50 values were 8.8, 6.6 and 6.3, respectively. The apparent affinities (-log KA) of (+/-)L-660,863) estimated by receptor inactivation, showed some selectivity toward the atrial M2 muscarinic receptor (-log KA = 7.6) in comparison to the M1 or M3 muscarinic receptors (-log KA = 5.4 and 6.2) respectively. This degree of selectivity was also observed in competition radioligand binding studies. 3. At M3 muscarinic receptors mediating inositol phosphates (IPs) accumulation in longitudinal muscle of guinea-pig ileum, the potency of (+/-)L-660,863 (-log EC50 value = 6.2) was similar to the apparent affinity calculated at M3 muscarinic receptors in the functional studies (see above). In contrast, at muscarinic receptors mediating IPs accumulation in guinea-pig atria and ventricles, the potency for (+/-)L-660,863 (-log EC50 = 6.2 and 6.4, respectively) was lower than the apparent affinity calculated at M2 muscarinic receptors from inotropic and binding studies in cardiac tissue (see above).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620241 TI - SDZ 205-557, a selective, surmountable antagonist for 5-HT4 receptors in the isolated guinea pig ileum. AB - A selective antagonist for the recently characterized 5-HT4 receptor is lacking. The only surmountable antagonist available, ICS 205-930, is a weak antagonist and is far more potent at 5-HT3-than at 5-HT4 receptors. In this paper, SDZ 205-557 (2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino) ethyl ester) is characterized as the first potent, selective and surmountable antagonist at 5-HT4 receptors in the isolated guinea pig ileum. SDZ 205-557 was investigated in the non-stimulated and in the field-stimulated guinea pig ileum longitudinal muscle preparation for its affinity for 5-HT4-, 5-HT3-, muscarine-, nicotine- and histamine H1 receptors. The affinity for 5-HT1-, 5-HT2-, alpha 1-, alpha 2- and opiate (mu) receptors was determined by binding assays. SDZ 205-557 was devoid of substantial affinity (pKD values below 5.6) for all receptors investigated except for 5-HT3- and 5-HT4 receptors. At these two receptors, SDZ 205-557 acted as an antagonist without measurable intrinsic activity. At the 5-HT4 receptors of the non-stimulated guinea pig ileum, responses to 5-HT and 5-methoxytryptamine were antagonized by SDZ 205-557 with identical pA2 values of 7.4. The effect of renzapride was also blocked with no significant change in the maximum response; Schild analysis, however, revealed that the interaction was not competitive with an "apparent" pA2 value of 7.6. A pA2 of 6.8 was obtained using zacopride as a contractile agent; this value differed significantly from 7.4, the value obtained for 5-HT and 5-methoxytryptamine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620242 TI - Relative contributions of ATP and noradrenaline to the nerve evoked contraction of the rabbit jejunal artery. Dependence on stimulation parameters. AB - Isotonic contractions of the rabbit jejunal artery were evoked by perivascular nerve stimulation with trains of 10 or 100 stimuli at 2 Hz or 10 Hz. Short trains of stimuli elicited contractions that were totally resistant to alpha adrenoceptor blockade (0.1 mumol/l prazosin) but blocked by alpha,beta-methylene ATP (1 mumol/l). A substantial noradrenergic component of contraction comprising about 50% of the total could be evoked by adjusting the stimulation parameters (increasing the frequency and/or number of stimuli in a train). The noradrenergic and the purinergic components are derived from sympathetic nerves as both were blocked by TTX and the adrenergic neurone blocker guanethidine (3 mumol/l). It is concluded that the contraction of the rabbit jejunal artery to short trains of stimuli is predominantly purinergic, a noradrenergic component only being revealed at higher frequencies of stimulation or during longer trains of stimuli. The purinergic component of contraction is derived from sympathetic nerves and not from a separate population of purinergic nerves. PMID- 1620243 TI - Is neuropeptide Y co-released with catecholamines in experimental arterial hypertension following sinoaortic denervation? AB - The release of catecholamines and their coneurotransmitter neuropeptide Y (NPY) was investigated in conscious dogs with neurogenic arterial hypertension elicited by sinoaortic denervation. One month after denervation, an elevation of catecholamine levels (measured by HPLC) without elevation of NPY-like immunoreactivity (NPY-LI) levels in plasma (evaluated by RIA) has been found. This dissociation could be explained by 1) a transient release of NPY during the first weeks after surgery, 2) a depletion of neuronal NPY due to the permanent sympathetic stimulation, or 3) an insufficient increase in sympathetic tone. To test these hypotheses, we investigated the time courses of catecholamine and NPY LI levels in arterial plasma during the first five weeks after sinoaortic denervation and responses to yohimbine (an alpha 2 antagonist which enhances transmitter release). Resting NPY-LI levels in plasma remained normal during the first five weeks after sinoaortic denervation. In normal dogs, a high dose of yohimbine (0.5 mg/kg i.v.) elevated both catecholamine (6-fold) and NPY-LI levels (1.5-fold), whereas a lower dose (0.05 mg/kg i.v.) induced a two fold elevation of catecholamine levels without changing NPY-LI concentrations. In sinoaortically denervated dogs, yohimbine elicited elevation of both catecholamines and NPY-LI whatever the dose used. Thus, neurogenic arterial hypertension in dogs seems to involve catecholamines but not NPY. Moreover, the present work suggests that a high level of sympathetic stimulation is required for a co-release of catecholamines and NPY. PMID- 1620244 TI - The force driving the extraneuronal transport mechanism for catecholamines (uptake2). AB - Recently, uptake2 was shown to exist in the clonal Caki-1 cell line. The aim of this study was two-fold: a) to determine, in Caki-1 cells, the intracellular fate of 3H-noradrenaline after its translocation by uptake2 and b) to analyse the force driving uptake2. Caki-1 cells have the characteristics of a "metabolizing system" in which the activity of catechol-O-methyl transferase (COMT) greatly exceeds that of monoamine oxidase (MAO). In all subsequent experiments these enzymes were inhibited. The determination of initial rates of uptake2 into Caki-1 cells at an extracellular pH between 6.9 and 7.9 indicated that the protonated species of 3H-noradrenaline is transported. Depolarization of Caki-1 cells (by three different procedures) inhibited the inward transport. Determination of the time course of the specific accumulation of 3H-noradrenaline in Caki-1 cells and of 3H-isoprenaline in the perfused rat heart (both mediated by uptake2) revealed that depolarization (by high K+) reduced the rate constant for inward transport (kIN) and increased that for outward movement (kOUT). Consequently, depolarization reduced the steady-state factor of accumulation. It is proposed that, as the protonated species of the substrates of uptake2 is transported, the membrane potential is likely to provide the driving force for uptake2. The fact that depolarization decreased kIN and increased kOUT agrees with this proposal, as do the magnitudes of the steady-state accumulation factors determined in Caki 1 cells and perfused rat heart. PMID- 1620245 TI - Inhibitory effects of the psychoactive drug modafinil on gamma-aminobutyric acid outflow from the cerebral cortex of the awake freely moving guinea-pig. Possible involvement of 5-hydroxytryptamine mechanisms. AB - The effects of modafinil on acetylcholine and GABA outflow from the cerebral cortex of awake freely moving guinea pigs provided with an epidural cup were studied. In the dose range of 3-30 mg/kg s.c. modafinil produced a dose dependent significant inhibition of GABA outflow without influencing cortical acetylcholine release. Methysergide (2 mg/kg, i.p.) and ketanserin (0.5 mg/kg, i.p.) but not prazosin (0.14 mg/kg, i.p.) counteracted the inhibitory action of modafinil on cortical GABA outflow. Modafinil both acutely and chronically in the same dose range increased striatal 5-HIAA levels and 5-HT utilization in the rat (acute) and mouse (chronic). The action on cortical GABA release may be dependent on activity at 5-HT2 receptors, since the action of modafinil in this respect is blocked by the non-selective 5-HT antagonist methysergide and the 5-HT2 antagonist ketanserin. The involvement of 5-HT mechanisms in the inhibitory action of modafinil on cortical GABA release is also suggested by the findings that 5-HT metabolism may become increased by modafinil at least in the striatum. The reduction of cortical GABA outflow via 5-HT2 receptors by modafinil is probably related to some of its actions on the central nervous system including behavioural effects. PMID- 1620246 TI - Attenuation of the morphine withdrawal syndrome by inhibition of catabolism of endogenous enkephalins in the periaqueductal gray matter. AB - We have investigated the effects of the local administration into the periaqueductal gray matter of thiorphan, a selective inhibitor of endopeptidase 24.11 "enkephalinase", kelatorphan, (R)-3-(N-hydroxy-carboxamido-2 benzylpropanoyl)- L-alanine, and RB 38 A, (R)-3-(N-hydroxy-carboxamido-2 benzylpropanoyl)-L-phenylalanine, two almost complete inhibitors of enkephalin metabolism, on the naloxone-precipitated morphine withdrawal syndrome in rats. Local administration of these inhibitors decreased the severity of the withdrawal syndrome. Jumping, chewing, diarrhea, piloerection, salivation and hypothermia were decreased by all drugs. Lacrimation and weight loss were reduced by kelatorphan and RB 38 A whereas teeth chattering, tremor, eye twitch and rhinorrhea were decreased only by RB 38 A. The rise in plasma corticosterone levels was only slightly reduced by the three inhibitors. Wet dog shakes and ptosis remained unchanged. These results indicate that during the morphine withdrawal syndrome in rats there is a tonic or/and naloxone evoked release of opioid peptides, presumably enkephalins, into the periaqueductal gray matter and that inhibition of their degradation strongly decreases the severity of the withdrawal syndrome. PMID- 1620247 TI - LG 6-101 and LG 6-102, two new propafenone-related antiarrhythmic agents with good oral activity in rats. AB - LG 6-101 (1-[3-(2-methoxy-3-(2-methylpropylamino)-propoxy)-4-methyl- 2-thienyl]-3 phenyl-1-propanon hydrochloride; MW: 426.02) and LG 6-102 (2-(2-methoxy-3 propylamino-propoxy)-3-phenyl-propiophenon hydrochloride; MW: 391.92) are two new antiarrhythmic substances. They are structurally related to propafenone which is a widely used class Ic-antiarrhythmic drug. In man the oral bioavailability of propafenone is only about 5-40%. Therefore the development of compounds with similar mode of action but higher oral bioavailability seems to be meaningful. Both, LG 6-101 and LG 6-102 proved to be effective in isolated auricles and in experimental animals after intravenous administration. In the present study we tested the antiarrhythmic effects of LG 6-101 and LG 6-102 in rats after oral administration. Animals were treated with LG 6-101 (16, 32, 64, 128, 256 mg kg-1 bodyweight), LG 6-102 (4, 8, 16, 32, 64 mg kg-1 bodyweight) and propafenone (32, 64, 128, 256 mg kg-1 bodyweight) by gavage twice daily during 4 days. Both, LG 6 101 and LG 6-102 showed strong antiarrhythmic effects against arrhythmias induced on the fifth day by infusion of aconitine (10 micrograms kg-1 min-1). LG 6-102 was significantly more effective against cardiac arrest caused by infusion of aconitine (P less than or equal to 0.05) than LG 6-101. Both substances had good effects on the delay of ventricular premature beats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620248 TI - Effect of dilazep dihydrochloride against ischemia and reperfusion-induced disruption of blood-brain barrier in rats: a quantitative study. AB - The effect of dilazep dihydrochloride (dilazep) against ischemia and reperfusion induced disruption of blood-brain barrier (BBB) was quantitatively investigated in Slc:Wistar strain rats using Evans blue dye as a BBB destruction indicator. The forebrain of sham-operated animal had a small amount of the dye. A treatment of 3.5-h ischemia plus 2-h reflow extravasated the dye into the brain and markedly increased the dye content as compared with that of sham group (P less than 0.01 vs. sham group). Continuous infusion (i.v.) of dilazep during cerebral ischemia dose-dependently reduced the increase of the dye content, and a significant reduction was found at 3 mg/kg/h (P less than 0.05 vs. control group). Evans blue dye extravasation after ischemia was also greatly reduced in saline-perfused brains by the treatment with dilazep. Dilazep has been reported to inhibit edema formation in cerebral ischemia model of spontaneously hypertensive rats. These results suggest that dilazep prevents the ischemic damage of BBB, which may contribute to reduction of the brain edema. PMID- 1620249 TI - [Achalasia and the possibility of cancer of the esophagus]. PMID- 1620250 TI - [Traumatology in The Netherlands]. PMID- 1620251 TI - [Indications and contraindications for artificial delivery]. PMID- 1620252 TI - [Hypercalcemia and malignancies; pathogenesis, differential diagnosis and treatment]. PMID- 1620253 TI - [Increased risk of heart and vascular diseases in fisherman from Urk]. AB - In order to assess physicians' preconceived ideas about unhealthy lifestyle of North Sea fishermen from Urk, the prevalence of five important risk factors for cardiovascular disease: hypertension, hypercholesterolaemia, smoking, obesity and diabetes mellitus was determined in a cross-sectional study in this population. In addition, the use of the Primetest device, a newly developed desk top analyser, was evaluated. Out of 646 people invited at the community centre at Urk, Flevoland, 384 (59%) fishermen were investigated using Primetest, which contains an electronic sphygmomanometer and colometrically determines total cholesterol and glucose levels. 87 laboratory determinations (with HDL cholesterol and triglyceride determinations) were used when Primetest cholesterol determination proved insufficiently reliable. Male cardiovascular mortality in Urk was also compared with mortality in the Netherlands. Hypertension prevalence (last of six readings) corresponded with that of the nearby town of Lelystad, 6% and 8% respectively. The average total:HDL-cholesterol ratio was not higher than recent values from elsewhere in the Netherlands. Fifty per cent of the fishermen had a high risk (ratio greater than 4.5). Of these, 18% had hypertriglyceridaemia (greater than or equal to 2.3 mmol/l). Smoking rates were very high (58%) and 60% had moderate to severe obesity (Body Mass Index greater than or equal to 26 kg/m2). 2% had diabetes mellitus, corresponding with the prevalence in the Netherlands. Absolute and proportional male cardiovascular mortality in Urk did not differ from the Netherlands. CONCLUSION: two risk factors had a high prevalence among Urk fishermen. Blood pressure measurements and glucose determination with Primetest are simple and reliable. For technical reasons reliable cholesterol determination was not yet possible. PMID- 1620254 TI - [Arterial injuries in lower leg fractures, a rare but severe complication]. AB - Vascular injuries of the popliteal or crural arteries complicating tibial fractures are rare. They often lead to acute critical limb ischaemia requiring immediate invasive diagnostic procedures and surgical repair. To illuminate the acute situation of this combined injury two case histories are presented. A comprehensive surgical approach is mandatory to salvage the injured limb. PMID- 1620255 TI - [Cardiovascular abnormalities in Marfan syndrome]. AB - During the period February to December 1990, 52 adult patients were referred to our clinic for evaluation of the presence of the Marfan syndrome. In 24 out of 52 patients the Marfan syndrome was diagnosed. Cardiac abnormalities were found in all patients: mitral insufficiency because of mitral valve prolapse (83%), aortic dilatation (67%), aortic insufficiency (38%), tricuspid valve insufficiency with or without tricuspid valve prolapse (17%) and atrial septal defect (4%). In 3 patients an aneurysm of the ascending aorta was found. Early recognition of the Marfan syndrome is relevant for prevention of the life threatening complication of aortic dissection. In patients with valve abnormalities endocarditis prophylaxis is advised. A Marfan outpatient clinic offers optimal diagnostic possibilities. PMID- 1620256 TI - [Villous adenoma of Vater's papilla; a therapeutic dilemma]. AB - After a cholecystectomy in 1980, local excision of a villous adenoma of the ampulla of Vater was performed in 1983 in a 69-year-old female; this had to be repeated in 1990 because of recurrence. In case of a tumour of this kind, pancreaticoduodenectomy should be considered because of the relatively high risk of recurrence or malignant degeneration. After a radical local excision regular duodenal endoscopy and if possible endoscopic ultrasonography should be performed. PMID- 1620257 TI - [Gluten as food additive in The Netherlands; Snowhite's apple?]. PMID- 1620258 TI - [Radio-synovectomy of the knee in chronic arthritis: a simple and sensible treatment]. PMID- 1620259 TI - [Medical activities under adverse conditions. Stimezo International]. PMID- 1620260 TI - [The thrombosis service as a source of information for studies in patients with heart valve prostheses]. PMID- 1620261 TI - [Influenza vaccination; encourage or wait and see?]. PMID- 1620262 TI - [Primary pneumococcal abscess in the Psoas muscle]. PMID- 1620264 TI - On changing relations with the PRO or belling the cat. PMID- 1620263 TI - [Urination problems following total hip arthroplasty: indwelling catheter or not?]. PMID- 1620265 TI - Endarterectomy for symptomatic carotid stenosis. Review of the European and North American Symptomatic Carotid Surgery Trials. AB - The recent results of two major multicenter trials, ECST (European Carotid Surgery Trialists') and NASCET (North American Symptomatic Carotid Endarterectomy Trial), show benefit of carotid endarterectomy for patients with recent (4-6 months), nondisabling, carotid distribution, cerebral ischemic events (hemispheric and retinal TIA or stroke) and ipsilateral severe (70-99%) carotid stenosis provided that perioperative mortality remains low. ECST, in addition, failed to demonstrate the benefit of surgery for patients with mild stenosis (0 29%). The comparisons between the studies in regards to methodology, measurements, and complications are discussed. PMID- 1620266 TI - Regression and stabilization of coronary artery lesions. Angiographic trials move beyond the NCEP treatment guidelines. AB - National Cholesterol Education Program Guidelines for the diagnosis and treatment of hypercholesterolemia have been formulated from population studies relating coronary events to blood lipids. Such population studies may not be relevant to patients with established coronary disease. Recent coronary angiographic studies allow meaningful comparisons of small groups of patients. These studies suggest that atherosclerotic lesions in coronary arteries can be stabilized, and further, that regression of coronary lesions can occur. The cholesterol and LDL levels achieved in angiographic studies are well below NCEP guidelines. Careful attention to correcting lipid abnormalities in patients with established coronary disease may alter the course of their illness. PMID- 1620267 TI - The effect of age on lipid composition and order of rat cerebral microvessels. AB - To determine if alterations in lipid composition and/or membrane order of cerebral microvessels may contribute to the age-related changes in blood-brain barrier (BBB) function, cerebral microvessels isolated from male Fischer 344 rats at 3 (young), 12 (intermediate age), and 24 (aged) months of age were studied. The steady state fluorescence polarization of diphenylhexatriene incorporated into isolated cerebral microvessel membranes at 35 degrees C, in aged rats was not different compared to young rats (0.2787 +/- 0.0029 vs 0.2847 +/- 0.0049). In addition, the thermotropic transition temperature of these membranes was not altered with age. Moreover, the fatty acid composition, the double bond index as well as cholesterol to phospholipid molar ratios were not significantly altered with age. In contrast, the concentration of conjugated dienes in lipid extracts of cerebral microvessels of aged rats (10.04 +/- 1.10 O.D./mg phospholipids) was significantly increased compared to the concentration in young rats (6.98 +/- 0.52 O.D./mg phospholipids) (p less than 0.01). It is concluded that aging is not associated with significant changes in lipid composition or membrane order of cerebral microvessels. However, the increased concentration of conjugated dienes in cerebral microvessels of aged rats is indicative on ongoing free radical damage in these microvessels which may contribute to the age-related changes in BBB function. PMID- 1620268 TI - 4-Bromoacetamidoprocaine: an affinity ligand for brain muscarinic and nicotinic cholinergic receptors. AB - This study describes the synthesis, receptor binding characteristics, and some behavioral effects of p-bromoacetamidoprocaine (BAP), a new affinity ligand for brain muscarinic and nicotinic cholinergic receptors. The reversible binding of [3H]QNB to rat brain membranes was inhibited in a concentration dependent and saturable manner by both procaine and BAP, with Ki values of 4 x 10(-6) and 3 x 10(-7) M, respectively, and complete inhibition at 1 x 10(-5) M. Both procaine and BAP, although at much concentrations, inhibited the binding of [3H]methylcarbamylcholine in a concentration dependent manner, with Ki values of 5 x 10(-5) and 1 x 10(-5) M, respectively, and complete inhibition for both at 1 x 10(-3) M. Plots of the % irreversible inhibition of [3H]QNB, [3H]nicotine, and [3H]MCC vs [BAP] yielded Ki values of 7 x 10(-8), 1 x 10(-4), and 6 x 10(-5) M, respectively. In behavioral studies BAP was able to antagonize the QNB-induced hyperactivity in mice; however, BAP did not appear to alter nicotine-induced seizure activity or other behavioral effects in mice. A plot of the time course of inhibition by BAP for [3H]QNB binding revealed that the inhibition was almost complete within 10 min exposure at 37 degrees. The findings indicate that BAP is a useful affinity ligand for examining the biochemical and functional characteristics of brain cholinergic receptors, particularly the muscarinic which has an affinity near the nM concentration range. PMID- 1620269 TI - Glutamate decarboxylase in developing rat neocortex: does it correlate with the differentiation of GABAergic neurons and synapses? AB - Postnatal development of glutamate decarboxylase was studied in the rat cerebral cortex. Two methods were used: estimation of the enzymatic activity of glutamate decarboxylase in homogenates of developing cortical tissue and visualization of structures containing glutamate decarboxylase-like immunoreactivity. Glutamate decarboxylase-like immunoreactivity appeared first in perikarya and dendrites and only later in axons and axon varicosities. The most rapid increase in the glutamate decarboxylase activity took place during the second postnatal week and this coincided with a rapid increase in the density of axon varicosities containing glutamate decarboxylase-like immunoreactivity but preceded the most rapid phase in the formation of GABAergic synapses by several days. However, there was a change in the characteristics of glutamate decarboxylase which correlated with GABA synaptogenesis: two fractions of glutamate decarboxylase with different sensitivities to the activating effects of Triton X-100 could be distinguished as from about the time when most of the GABAergic synapses are formed. PMID- 1620270 TI - Effect of corticosterone on noradrenergic nuclei in the pons-medulla and [3H]NA release from terminals in hippocampal slices. AB - The aim of the present study was to investigate possible membrane and genomic effects of corticosterone on the noradrenergic system of the rat brain. Corticosterone effects were studied in vivo by treating rats s.c. with 10 mg/kg corticosterone for 7 or 14 days. In the first two experiments corticosterone significantly decreased the noradrenaline (NA) and dopamine (DA) levels in the pons-medulla, an area which contains the A1-A7 noradrenergic cell groups, while the NA and DA levels in the dorsal hippocampus remained unchanged. In a third experiment where the locus coeruleus (LC) and the A1 and A2 nuclei (A1,A2) were analysed separately, NA levels were unchanged but total MHPG levels and the total MHPG/NA ratio were decreased in the A1,A2 area. Chronic corticosterone treatment (14 days) did not alter the alpha 2-adrenoceptor-mediated modulation of [3H]NA release from dorsal hippocampal slices. Neither the spontaneous outflow nor the electrically stimulated release of [3H]NA from dorsal hippocampal slices of untreated rats was affected by exposure of the slices to corticosterone (10(-7) M - 10(-4) M) in the superfusion buffer. Thus, chronic corticosterone treatment of rats altered the noradrenergic system of the pons-medulla, but did not change the alpha 2-adrenoceptor-mediated modulation of NA release in the dorsal hippocampus, a major terminal area of the LC neurons. Corticosterone also did not appear to have a direct membrane effect on the NA terminals in the dorsal hippocampus of the rat. PMID- 1620272 TI - Developmental change of an enzyme activity oxidizing gamma-aminobutyraldehyde to gamma-aminobutyric acid in the chick embryonic brain. AB - An enzyme activity oxidizing gamma-aminobutyraldehyde (ABAL) to GABA reflecting an alternative pathway for GABA synthesis was assayed in the developing chick embryonic brain and was compared with glutamate decarboxylase (GAD) activity. An enzyme activity oxidizing ABAL to GABA showed almost constant level during development in the chick embryonic brain, and was present at low levels compared with GAD activity. The results indicate that GABA synthesis via an alternative pathway is always much less than synthesis via the GAD-dependent pathway in the developing chick embryonic brain. PMID- 1620271 TI - Primary structure of an agonist binding subunit of the nicotinic acetylcholine receptor from bovine adrenal chromaffin cells. AB - Activation by acetylcholine of a nicotinic acetylcholine receptor on the membrane of bovine chromaffin cells leads to membrane depolarization and to the subsequent triggering of catecholamine secretion. It is evident that acetylcholine receptors play a central role in the initial phase of the secretion process and, therefore, an extensive characterization of their molecular components and properties is of fundamental interest. With this intention, we have screened bovine adrenal medullary cDNA libraries with a probe coding for a fragment of the rat muscle acetylcholine receptor alpha subunit. Several cDNA clones were isolated. The longest cDNA had an open reading frame encoding a 495-amino acid protein with a molecular weight of 56,911. The deduced primary structure contains features that indicate that the encoded protein is an alpha or acetylcholine binding subunit, and, in fact, it manifests significant sequence similarity to previously cloned alpha subunits. Sequence identity is particularly high with the alpha 3 subunit, which is expressed in the rat pheochromocytoma PC12 cell line and in several brain areas, and, consequently, it is considered a component of a neuronal acetylcholine receptor. Accordingly, the present results suggest that the agonist binding subunit of the nicotinic acetylcholine receptor from bovine chromaffin cells is an alpha 3-type subunit, corroborating previous immunological and pharmacological evidence for the presence of a neuronal nicotinic receptor in chromaffin cells. PMID- 1620274 TI - Quantifying the pattern of beta/A4 amyloid protein distribution in Alzheimer's disease by image analysis. AB - We have undertaken a study of the distribution of the beta/A4 amyloid deposited in the cerebral cortex in Alzheimer's disease. Previous studies which have examined the differential distribution of amyloid in the cortex in order to determine the laminar pattern of cortical pathology have not proved to be conclusive. We have developed an alternative method for the solution of this problem. It involves the immunostaining of sections followed by computer-enhanced image analysis. A mathematical model is then used to describe both the amount and the pattern of amyloid across the cortex. This method is both accurate and reliable and also removes many of the problems concerning inter and intra-rater variability in measurement. This method will provide the basis for further quantitative studies on the differential distribution of amyloid in Alzheimer's disease and other cases of dementia where cerebral amyloidosis occurs. PMID- 1620273 TI - Cerebral vasculopathy in divers. AB - Brains from 12 amateur and 13 professional divers, all but one of whom died accidentally, were examined neuropathologically. Grossly distended, empty vessels (presumably caused by gas bubbles) were found in the brains of 15 out of 22 divers who died from diving accidents. Perivascular lacuna formation was found in cerebral and/or cerebellar white matter in three amateurs and in five professionals. In addition to lacuna formation, hyalinization of vessel walls was present in the brains of three amateurs and five professionals. Necrotic foci in grey matter occurred in seven cases and perivascular vacuolation of white matter occurred in seven cases. The vascular changes probably arose from intravascular gas bubble formation. In one professional diver, there was also unilateral necrosis of the head of the caudate nucleus. PMID- 1620275 TI - Ultraviolet irradiation induced brain oedema in rats. A microgravimetric study. AB - The cerebral cortex of 36 anaesthetized Wistar rats were exposed to ultraviolet irradiation (UV-I) for 6 min through a 2 x 2 mm left parietal craniotomy. Animals were killed at different times and brains were removed immediately after death. Three consecutive coronal sections were obtained and sampled for gravimetric study. The density of the samples was measured using a continuous gradient of organic solvents. Gravimetric results showed significant differences between brain samples. The irradiated left hemisphere was less dense than the right one, and maximum differences in density were found in the medial coronal section. Grey and white matter oedema in the non-irradiated hemisphere was compared with the irradiated hemisphere. Early and delayed onset of odema was observed in both hemispheres but it was more marked in the irradiated hemisphere. In conclusion, brain oedema induced by ultraviolet irradiation in various animals is also reproducible in rats with all the advantages involved in the use of these experimental animals. Microgravimetric study correlated with topographical analysis using this model may lead to an understanding of some of the dynamic aspects of cerebral oedema. PMID- 1620276 TI - Molecular genetic study showing that the IN/157 'oligodendroglioma' cell line has been contaminated by rhabdomyosarcoma (RD) cells. AB - The IN/157 cell line was originally isolated from a human oligodendroglioma biopsy and has been used in recent years to study aspects of glioma cell biology. We established that IN/157 cells carry a relatively infrequent mutation at position three of codon 61 of the N-ras gene, suggesting that such a mutation may have contributed towards the genesis of the original tumour. However, the mutation was not detectable within the original paraffin-embedded glioma biopsy from which the cell line was supposedly derived. We thus considered the possibility that the cells had been contaminated by another cell line and, by means of DNA fingerprinting, have demonstrated that the contaminating cell line is the rhabdomyosarcoma line RD. We feel that this study makes several important points regarding experiments which make use of cell lines. We discuss the possible implications of contamination events with regard to erroneous conclusions about the biology of the cell lines and tumour types from which they supposedly derive. We also suggest ways in which future contamination-related errors can be minimized. PMID- 1620277 TI - Neuropathological findings in chronic relapsing experimental allergic neuritis induced in the Lewis rat by inoculation with intradural root myelin and treatment with low dose cyclosporin A. AB - Experimental allergic neuritis (EAN) was induced in Lewis rats by inoculation with bovine intradural root myelin and adjuvants. Rats treated with subcutaneous cyclosporin A (CsA) (4 mg/kg on 3 days per week from the day of inoculation until day 29) developed a chronic relapsing course. Tissues from the spinal cord, nerve roots, dorsal root ganglia and sciatic nerve of CsA-treated rats sampled during relapses and remissions were studied by light and electron microscopy. Control rats that were not treated with CsA were studied during or after episodes of acute EAN. Both control and CsA-treated animals studied in the first episode of EAN had evidence of inflammation and primary demyelination of the nerve roots and dorsal root ganglia. In control and CsA-treated animals that had recovered from the first episode there was evidence of remyelination. In CsA-treated animals in the second episode there was severe inflammation and demyelination and remyelination of the nerve roots and dorsal root ganglia, and in addition there was significant demyelination and remyelination in the spinal nerves and sciatic nerves and dorsal columns of the spinal cord, particularly in later stages of disease. In later episodes there was less inflammation, but there was continuing demyelination and onion bulbs were present. In animals sampled after recovery from chronic relapsing EAN onion bulbs were present. Occasional small onion bulbs were also observed in control animals that were inoculated with higher doses of myelin. Plasma cells were present in the inflammatory lesions of later episodes. Mast cells were also observed at different stages of the disease. We conclude that the CsA form of chronic relapsing EAN has clinical and pathological similarities with the human disease, chronic inflammatory demyelinating polyradiculoneuropathy. PMID- 1620278 TI - The behaviour of meningeal cells following glial cell transplantation into chemically-induced areas of demyelination in the CNS. AB - Following transplantation of cultures of CNS glia containing leptomeningeal cells into ethidium bromide-induced demyelinating lesions, meningeal cells adopt either compacted or diffuse arrangements. The compacted arrangements involved no interactions with other cellular components of the remyelinating environment, and were particularly prominent following transplantation of cultures containing a high proportion of fibronectin-positive meningeal cells. The diffuse arrangements involved interactions with astrocytes, Schwann cells and endothelial cells, and contributed to a fragmented appearance of the lesion. Such observations indicate that meningeal cell contamination should be avoided when attempts are being made to repopulate glial-deficient lesions in the CNS by transplanting central glial cells, since their effect is to partition the glial environment. PMID- 1620279 TI - Acute bilateral ballism in a patient with intravascular dissemination of gastric carcinoma. AB - An 84-year-old woman presented with an acute onset of violent bilateral ballism chorea. She was admitted to the local neurology unit, but not definite diagnosis could be made of the underlying condition, although she did appear to have bronchopneumonia. At autopsy the stomach wall was thickened, and the lesser curve lymph nodes were firm and enlarged. A single nodule was noted in the liver while the lungs appeared consolidated. Histology revealed a moderate-to-poorly differentiated gastric adenocarcinoma with extensive intravascular dissemination which included the central nervous system (CNS). Numerous small infarcts related to vessels occluded by tumour were present throughout the brain, and we feel that this was the underlying mechanism for the acute onset of ballism. PMID- 1620280 TI - Desmoplastic spindle-cell glioblastoma or gliosarcoma? PMID- 1620281 TI - The polymerase chain reaction and its applications in neuropathology. AB - The polymerase chain reaction (PCR) provides a means of generating large numbers of copies of selected segments of DNA. Once amplified, the DNA can be characterized by determination of its size and sequence. For many applications, routinely-processed biopsy and autopsy material is an adequate substrate for the reaction. PCR can be used to amplify sequences of DNA that are uniquely characteristic of particular micro-organisms, allowing their rapid detection in samples of tissue or cerebrospinal fluid. The technique allows clones of cells with gene rearrangements or translocations to be detected with great sensitivity and is proving a useful way to monitor the effects of tumour therapy, particularly in patients with lymphomas and leukaemias. Further applications include the identification of gene deletions and mutations, and the assessment of cell lineage by amplification and analysis of highly polymorphic gene loci (DNA fingerprinting). Because the degree of amplification resulting from PCR is so great, even a single molecule of contaminating DNa may be detected and its significance misinterpreted. Great care, therefore, should be taken to prevent contamination of samples, particularly by the products of previous reactions, and every series of reactions should include appropriate controls. PMID- 1620283 TI - Differences in extracellular calcium involvement mediating the secretion of gonadotropin and growth hormone stimulated by two closely related endogenous GnRH peptides in goldfish pituitary cells. AB - Two endogenous gonadotropin-releasing hormone (GnRH) peptides, salmon GnRH (sGnRH) and chicken GnRH II (cGnRH II), stimulate gonadotropin (GtH) and growth hormone (GH) secretion in the goldfish. The extracellular calcium (e-Ca2+) dependence of the GtH and GH response to the two GnRH peptides were compared using static incubations of dispersed goldfish pituitary cells. Incubation with Ca(2+)-depleted medium (without the addition of Ca2+ salts and in the presence of EGTA) did not alter basal GtH secretion, but reduced the GtH response to sGnRH, and abolished the cGnRH II-induced GtH release. Blockade of e-Ca2+ entry by low concentrations of CoCl2 had no effect on basal GtH secretion but reduced cGnRH II and sGnRH stimulated GtH release when applied at 0.1 and 0.5 mM concentrations, respectively. In general, treatments with voltage-sensitive Ca2+ channel (VSCC) antagonists, verapamil, nifedipine and nicardipine, did not alter basal GtH release but attenuated GnRH-stimulated GtH responses. cGnRH II-induced GtH release was decreased by 10 nM verapamil and 1 nM nifedipine, whereas the reduction of GtH responses to sGnRH required 100 times higher concentrations of these VSCC antagonists. cGnRH II but not sGnRH stimulation of GtH secretion was also abolished by 10 microM nicardipine. In contrast to GtH release, exposure to Ca(2+)-depleted medium reduced basal GH release and abolished the GH responses to both GnRH peptides. sGnRH and cGnRH II-stimulated GH responses were both abolished by 0.1 mM CoCl2, decreased by 1 nM verapamil, and reduced by 10 nM nicardipine. Addition of 0.1 and 10 microM nifedipine inhibited the GH responses to sGnRH and cGnRH II, respectively. Basal GH release was not affected by the VSCC antagonists tested. Results from this study indicate that entry of e-Ca2+, in part through VSCC, is involved in GnRH stimulation of GtH and GH release from goldfish gonadotropes and somatotropes; however, the e-Ca2+ dependence of the GtH and GH responses to the two endogenous GnRHs differ. The stimulatory effects of cGnRH II on GtH secretion is more dependent on and sensitive to e-Ca2+ than sGnRH. Whereas the sensitivity of GH responses to manipulations of e-Ca2+ availability is, in most instances, similar for both GnRH peptides. These results further suggest that basal secretion of GH is more sensitive to e-Ca2+ than basal GtH release; however, VSCC are not involved in the maintenance of basal release of either hormone. PMID- 1620282 TI - Immunocytochemical study of GnRH and GnRH-associated peptide in male Syrian hamsters as a function of photoperiod and gonadal alterations. AB - Hypothalamic luteinizing-hormone-releasing hormone (GnRH) and gonadotropin releasing-hormone-associated peptide (GAP) biosynthesis and storage were estimated by immunocytochemistry in male golden hamsters maintained in different photoperiods. Intact or castrated male hamsters with subcutaneously inserted testosterone implants were exposed to long-day (14:10) or short-day photoperiods (10:14) for 4-8 weeks. Exposure to short photoperiod for 4 weeks, an interval characterized by a suppression of gonadotropin secretion but not gonadal regression, was associated with an increase in the number of GnRH- and GAP immunoreactive cells in the diagonal band of Broca/medial septum. Furthermore, morphometric analysis revealed that these animals displayed significantly more GnRH but not GAP immunoreactivity in the median eminence as opposed to hamsters exposed to long-day photoperiods. In additional studies, gonadally regressed hamsters exposed to short day lengths for 8 weeks had equal numbers of GnRH cells as did the long-day controls. These patterns suggest that reproductive quiescence in golden hamsters is not the result of depletions of neuronal GnRH stores available for secretion. PMID- 1620285 TI - Steroid hormones and steroid hormone binding globulins in cerebrospinal fluid studied in individuals with intact and with disturbed blood-cerebrospinal fluid barrier. AB - We measured in simultaneously withdrawn cerebrospinal fluid (CSF) and serum samples from 56 endocrinologically grossly normal patients the concentrations of several lipophilic unconjugated steroids [i.e. dehydroepiandrosterone (DHEA), androstenedione, cortisol, progesterone, testosterone] and their hydrophilic counterparts, i.e. DHEA-sulfate, or hydrophilic binding proteins, i.e. albumin, sex hormone-binding globulin (SHBG) and corticosterone-binding globulin (CBG). CSF levels of total (i.e. free plus protein-bound) DHEA, androstenedione, cortisol, progesterone, and testosterone were found to be in the 0.02-2 nM range and only cortisol reached levels approximately 20 nM. These values were of the same order of magnitude as the reported and calculated free serum levels of these steroids. In patients with disturbed (abnormally leaky) blood-CSF barrier (BCB) function, CSF levels of these steroids were not different from those with intact BCB, in contrast to DHEA-sulfate, CBG and SHBG whose CSF levels were significantly elevated, that is similar (i.e. 2-5) fold as those of albumin. In vitro demonstrated low affinity (micromolar) interactions of steroids with neuronal membrane-bound neurotransmitter receptors should be considered in perspective to the here reported finding that steroids occur in vivo at best in nanomolar concentrations in the CSF. Whether in other extracellular fluid compartments of the brain higher levels of steroids than in CSF can accumulate is as yet not clear. Very probably, pathological production or excessive dosage of steroids that are negligibly bound to SHBG or CBG will produce CSF and brain levels in the near micromolar range. PMID- 1620284 TI - Estradiol regulation of proopiomelanocortin gene expression and peptide content in the hypothalamus. AB - Previous studies have shown that the hypothalamic concentrations of beta endorphin (beta-EP) and other proopiomelanocortin (POMC)-derived peptides change in the female rat following castration and gonadal steroid replacement. In this study we have measured POMC mRNA by solution hybridization assay in the medial basal hypothalamus (MBH) of ovariectomized rats treated with a regimen of estradiol (E2) that we have previously shown alters brain beta-EP peptide content. In addition the effect of progesterone (P) was also studied. In the first experiment the concentration of beta-EP and alpha-melanocyte-stimulating hormone (alpha-MSH) in the MBH of castrated rats decreased significantly after 3 weeks of E2 treatment compared to castrated unreplaced rats: beta-EP decreased from 6.00 +/- 0.46 to 4.32 +/- 0.38 ng/mg protein and alpha-MSH decreased from 3.00 +/- 0.23 to 2.35 +/- 0.15 ng/mg protein (p less than 0.05). A similar decrease in peptide content was noted in the anterior hypothalamus/preoptic area. A parallel reduction in the concentration of POMC mRNA was measured in the MBH of the E2-replaced animals: 1.17 +/- 0.14 vs. 0.72 +/- 0.08 pg/microgram RNA (p less than 0.02). In a second study castrated rats were studied after 2 weeks of E2 or E2 plus P treatment. After 2 weeks, POMC peptide levels did not change significantly in the MBH of either the E2- or E2 plus P-treated rats. POMC mRNA, however, was significantly reduced from 1.10 +/- 0.10 pg/micrograms RNA in the unreplaced rats to 0.58 +/- 0.05 and 0.61 +/- 0.06 pg/microgram RNA after E2 or E2 plus P, respectively (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620286 TI - Contribution of the region anterior and ventral to the third ventricle to opiate withdrawal excitation of oxytocin secretion. AB - Virgin female or lactating rats were given infusion into a lateral cerebral ventricle (i.c.v.) of either morphine to produce tolerance and dependence or vehicle from a subcutaneous osmotic minipump for 5 days, then they were anaesthetized with urethane. In virgins either an electrolytic or sham lesion of the region anterior and ventral to the third ventricle (AV3V region) was made. Initial blood plasma concentrations of oxytocin, measured by radioimmunoassay were similar in i.c.v. morphine- and i.c.v. vehicle-infused rats (20.6 +/- 2.7 and 19.0 +/- 4.3 pg/ml, respectively). Naloxone (5 mg/kg i.v.) significantly increased oxytocin secretion in all groups for at least 60 min; oxytocin concentration at 6 min after naloxone was in the order: sham-lesioned i.c.v. morphine group (mean 1,839 +/- 809 pg/ml, n = 6), greater than AV3V-lesioned i.c.v. morphine group (326 +/- 65 pg/ml, n = 6), = sham-lesioned i.c.v. vehicle group (251 +/- 66 pg/ml, n = 6), greater than AV3V-lesioned i.c.v. vehicle group (47.2 +/- 12.4 pg/ml, n = 6). Thus in both intact and lesioned rats naloxone increased oxytocin secretion much more in morphine-dependent rats than in the respective controls; in both morphine-naive and morphine-dependent rats, the AV3V lesion reduced the effect of naloxone with respect to plasma oxytocin concentration, but not with respect to the increase relative to the lower prenaloxone concentrations in the lesioned rats (prenaloxone values in the lesioned rats were: i.c.v. vehicle group, 15.8 +/- 6.8 pg/ml; i.c.v. morphine group, 24.3 +/- 7.8 pg/ml; and in the sham-lesioned rats: i.c.v. vehicle group, 67.3 +/- 31.2 pg/ml, i.c.v. morphine group, 65.5 +/- 15.0 pg/ml). Thus the AV3V region is not essential for withdrawal excitation of oxytocin secretion in morphine-dependent rats. In lactating morphine-dependent rats, i.c.v. infusion of the angiotension II antagonist saralasin (2.5 micrograms/min) decreased plasma oxytocin concentration after 10 min (5.7 +/- 1.1 pg/ml, n = 7 vs. 13.2 +/- 3.2 pg/ml, n = 8), but did not prevent naloxone-provoked excitation of oxytocin secretion, measured by radioimmunoassay (6 min after naloxone in the i.c.v. saralasin group 402.8 +/- 124.5 pg/ml, n = 7 vs, in controls, 1,009 +/- 382 pg/ml, n = 7) or assessed by continuous recording of intramammary pressure. These results indicate that centrally acting angiotensin II is not an important mediator of naloxone-induced oxytocin hypersecretion in morphine-dependent rats.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1620287 TI - Neurotrophic effects of fibroblast growth factors on peptide-containing neurons in culture from postnatal rat hypothalamus. AB - Basic fibroblast growth factor (bFGF) has been thought to act as a neurotrophic factor during early developmental stages in various brain regions, including the hypothalamus. In the present paper, we have studied the effect of bFGF on peptide containing neurons cultured from the postnatal (1-3 days and 14 days after birth) rat hypothalamus. The addition of bFGF, or acid FGF (aFGF), to serum-free culture medium increased both survival and neurite growth of growth hormone-releasing factor (GRF)-containing neurons. The potency of bFGF was more than 10 times as great as that of aFGF. Insulin-like growth factor I (IGF-I) did not have any significant effect on the survival of GRF neurons. Further, neither IGF-I nor aFGF modified the survival-promoting effect of bFGF on GRF neurons. bFGF promoted the survival of somatostatin- and vasoactive intestinal polypeptide-containing neurons, too. PMID- 1620288 TI - Binding sites for interleukin-6 in the anterior pituitary gland. AB - Interleukin-6 (IL-6) binding site in the rat anterior pituitary gland was characterized using radioiodinated human recombinant (hr) IL-6. Results showed that the anterior pituitary gland contained 170 binding sites per cell of a single class with a dissociation constant of 2.7 x 10(-9) M. The binding of 125I hrIL-6 to the rat anterior pituitary gland was competitively inhibited by unlabeled hrIL-6, but not by hrIL-1 alpha, hrIL-1 beta, hrIL-2 or hr-interferon gamma, indicating these binding sites are specific for IL-6. We also demonstrated mouse IL-6 receptor gene expression in the rat anterior pituitary gland by Northern blot analysis. Furthermore, the IL-6 receptor was detected on human gonadotrophs by the double immunofluorescence method. Our findings demonstrate the presence and expression of IL-6 binding site in the rat anterior pituitary gland and the presence of IL-6 binding site on human gonadotrophs, suggesting the important role of IL-6 binding site in pituitary hormone release in both species. PMID- 1620289 TI - Opiate modulation of growth hormone secretion is compromised during the steroid induced luteinizing hormone surge. AB - Earlier studies from our laboratory have shown that treatments with gonadal steroids which cause a surge of luteinizing hormone (LH) blunt the effects of morphine on LH secretion, locomotor activity, nociception and temperature regulation. The present study was conducted to determine if the growth hormone (GH) response to morphine sulfate (MS) was also affected during steroid-induced LH surges. Adult ovariectomized female rats were primed with estradiol benzoate (EB: -49 h prior to P4 or oil injection) and/or progesterone (P4; 10.00 h). Seven and one half hours after P4 treatment, at the time of the steroid-induced LH surge, the GH response to an intravenous dose of 0.5, 2.0 or 5.0 mg/kg MS was determined. A GH peak response occurred at 15 min after drug administration and was maximal at the dose of 2 mg/kg MS in all groups. Although the timing of the GH rise was not altered in either EB/oil- or EB/P4-treated animals, a significant blunting of MS-induced GH secretion was observed across all doses of MS with a greater reduction being observed in EB/P4-treated animals. In a second study the GH response to opiates was investigated prior to and following the steroid induced LH surge to determine if the suppression of opiate-induced GH secretion was confined to the time of the preovulatory LH surge. Before the LH surge (2.5 h), a mild suppression of opiate-induced GH secretion was observed only in EB/oil treated animals. After the LH surge (13 h after P4 administration), morphine induced GH secretion was similar in all groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620290 TI - Purification and characterization of urotensin II and parvalbumin from an elasmobranch fish, Scyliorhinus canicula (common dogfish). AB - The caudal portion of the spinal cord of elasmobranch fish incorporates a diffuse neuroendocrine system. Using an antiserum raised against urotensin II from a teleost fish (goby) to facilitate purification, a peptide structurally related to urotensin II was isolated in pure form from an extract of neuroendocrine tissue from the spinal cord of the European common dogfish, Scyliorhinus canicula. The primary structure of the peptide was established as: Asn-Asn-Phe-Ser-Asp-Cys-Phe Trp-Lys-Tyr-Cys-Val. The amino acid sequence was confirmed by chemical synthesis. A comparison of this sequence with those of the known teleost urotensin II peptides shows that the cyclic region of the molecule has been fully conserved between species and suggests that the presence of an acidic residue at position 5 and a hydrophobic residue at position 12 are important features for the biological activity of the peptide. The dogfish spinal cord extract also contained a high concentration of the calcium-binding protein, parvalbumin and the amino acid sequence at its NH2 terminus [residues (1-50)] was determined. PMID- 1620291 TI - Sustained release of nerve growth factor from biodegradable polymer microspheres. AB - Although grafted adrenal medullary tissue to the striatum has been used both experimentally and clinically in parkinsonism, there is a definite need to augment long-term survival. Infusion of nerve growth factor (NGF) or implantation of NGF-rich tissue into the area of the graft prolongs survival and induces differentiation into neural-like cells. To provide for prolonged, site-specific delivery of this growth factor to the grafted tissue in a convenient manner, we fabricated biodegradable polymer microspheres of poly(L-lactide)co-glycolide (70:30) containing NGF. Biologically active NGF was released from the microspheres, as assayed by neurite outgrowth in a dorsal root ganglion tissue culture system. Anti-NGF could block this outgrowth. An enzyme-linked immunosorbent assay detected NGF still being released in vitro for longer than 5 weeks. In vivo immunohistochemical studies showed release over a 4.5-week period. This technique should prove useful for incorporating NGF and other growth factors into polymers and delivering proteins and other macromolecules intracerebrally over a prolonged time period. These growth factor-containing polymer microspheres can be used in work aimed at prolonging graft survival, treating experimental Alzheimer's disease, and augmenting peripheral nerve regeneration. PMID- 1620292 TI - The role of immediate operative intervention in severely head-injured children with a Glasgow Coma Scale score of 3. AB - In an attempt to improve and expedite the care of head-injured children, data have been published recommending burr hole exploration in lieu of computed tomography for children with signs of brain stem compression or with a Glasgow Coma Scale score of 3. Exploratory burr holes revealed a high incidence of subdural hematomas, and removal of the hematomas improved survival. We are reporting 19 consecutive children with Glasgow Coma Scale scores of 3. Coma score evaluation was confounded by intubation, sedation, pharmacological paralysis, and posttraumatic seizures. We found no radiographical or postmortem pathological evidence of intracranial hemorrhage, which would warrant operative intervention. A high incidence of multisystem injuries and high cervical spine injuries would have made early intervention both dangerous and inappropriate. Although there is a definite role for emergency trephination, routine exploratory burr holes for children with a Coma score of 3 is not justified. PMID- 1620293 TI - Microsurgical and magnetic resonance imaging anatomy of the cerebello-medullary fissure and its application during fourth ventricle surgery. AB - The cerebellomedullary fissure, the only entrance or exit to the fourth ventricle, is surrounded rostrally by the cerebellar tonsils and the biventral lobules and caudally by the medulla oblongata, the tela choroidea, and the lateral recesses. This fissure is an important route in operations on the fourth ventricle. We studied the microsurgical and magnetic resonance imaging (MRI) anatomy of the fissure by using autopsied normal cerebellum. MRI revealed that the fissure is visible as a slit and is indicated by the enhanced choroid plexus and the flocculus. Oriented by the anatomical information thus obtained, we have surgically treated nine patients with a tumor either in or around the fourth ventricle. Preoperative MRI clearly demonstrated the tumors in relation to the cerebellomedullary fissure. It revealed the precise anatomical location and extension of the tumor, not only its inferior extension but also its lateral one. The MRI findings and microsurgical anatomy of the cerebellomedullary fissure were quite useful for the removal of the tumors in the fourth ventricle. PMID- 1620294 TI - The permeability change of major cerebral arteries in experimental vasospasm. AB - The influence of vasospasm on the permeability of the major cerebral arteries was studied using horseradish peroxidase (HRP). Experimental vasospasm was produced in canine basilar arteries by successive injections, 2 days apart, of autologous blood into the cisterna magna. HRP was injected intravenously or intracisternally 48 hours after the second injection of autologous blood, and all animals were killed by perfusion fixation 60 minutes after the injection of HRP. The distribution of HRP was observed by transmission electron microscopy. In 10 dogs injected intracisternally with HRP, 5 control dogs demonstrated a moderate amount of HRP in the intermuscular space through the adventitia. Five dogs with subarachnoid hemorrhages (SAHs) showed a moderate amount of HRP in the intermuscular space. In 11 dogs injected intravenously with HRP, 5 control dogs showed no leakage of HRP into vessel walls. Six dogs with SAHs showed HRP in the interendothelial space. These findings suggest that, despite SAHs, HRP seems to be able to circulate in the cerebrospinal fluid and makes contact with the cerebral vessels. This study suggests the possibility that spasmogenic substances may penetrate the vessel wall from the extraluminal side more easily than from the intraluminal side. PMID- 1620295 TI - Accelerated nonmuscle contraction after subarachnoid hemorrhage: culture and characterization of myofibroblasts from human cerebral arteries in vasospasm. AB - Cell culture lines from human cerebral arteries showing vasospasm after subarachnoid hemorrhage were established from three autopsy cases. Each culture line showed the ultrastructural characteristics of myofibroblasts. Decreased alpha-actin antigenicity, demonstrated using the anti-smooth muscle cell alpha actin antibody, was observed in cultured cells possessing abundant F-actin. When incorporated into the three-dimensional collagen matrix in vitro, the cultured cells compacted the collagen lattice at a rate equivalent to that of human dermal fibroblasts. Lattice compaction was significantly accelerated by cerebrospinal fluid taken from patients with symptomatic vasospasm. Compaction was completely inhibited by the addition of 10(-6) mol/L verapamil or 100 U/mL heparin. Neither nimodipine (10(-5) mol/L) nor nicardipine (10(-5) mol/L) inhibited compaction, and endothelin (10(-6) mol/L) and potassium chloride (40 mmol/L) had no effect. The morphological change of cells in the collagen lattice suggests that both verapamil and heparin affect cellular motility, filopodial protrusion, and cell attachment. These data suggest that myofibroblasts in human cerebral arteries differ from medial smooth muscle cells and can generate a force rearranging the proliferated collagen matrix present after subarachnoid hemorrhage. This reorganization can contribute to, or be responsible for, sustained vasoconstriction. Consequently, current treatment for vasospasm may need to be reevaluated to include the nonmuscle components in the vessel wall. PMID- 1620296 TI - Time course of changes in concentration of intracellular free calcium in cultured cerebrovascular smooth muscle cells exposed to oxyhemoglobin. AB - A culture of smooth muscle cells obtained from monkey middle cerebral arteries was developed to allow quantitative assessment of intracellular calcium and immunofluorescence analysis after various periods of exposure to oxyhemoglobin. Intracellular calcium concentration was examined for up to 7 days after a single exposure to oxyhemoglobin. Intracellular calcium concentrations were measured with the fluorescent dye fura-2 and were significantly elevated for 7 days after exposure to oxyhemoglobin (P less than 0.01). Less than 2 minutes after application of oxyhemoglobin, there was marked elevation of intracellular calcium from the control value of 75 +/- 2 nmol/L to 240 +/- 28 nmol/L (P less than 0.01 by analysis of variance). Intracellular calcium concentration of cells exposed for 24 hours to oxyhemoglobin and then grown in normal oxyhemoglobin-free medium fell close to normal levels on Days 3 and 7. On Day 3, the increase in intracellular calcium that followed repeated daily exposure to oxyhemoglobin was greater than that resulting from a single application of oxyhemoglobin (P less than 0.01 by Student's t test), but by Day 7 the elevation produced by these different approaches was similar. Smooth muscle cells exposed to oxyhemoglobin showed a reduction in immunoreactivity to alpha-actin. These data support the hypothesis that disruption of intracellular calcium regulation and calcium overloading may be important in the process of cell injury, which results in vasoconstriction and sometimes cell death, after exposure to oxyhemoglobin. PMID- 1620297 TI - Preventive effect of synthetic serine protease inhibitor, FUT-175, on cerebral vasospasm in rabbits. AB - The effect of the synthetic multiserine protease inhibitor FUT-175 on cerebral vasospasm after subarachnoid hemorrhage (SAH) was investigated in rabbits. The SAH in rabbits was simulated by a single injection of autologous arterial blood into the cisterna magna, and, for 7 days, the caliber of each basilar artery was examined several times via angiogram. In 10 SAH rabbits, the peak of the arterial narrowing was observed on Day 2. In this model, the effect of intravenous administrations of FUT-175 was examined. Twenty-seven SAH rabbits were randomly divided into three groups, and 3 doses of 1, 2, or 3 mg of FUT-175 were administered intravenously. Angiographic arterial narrowing on Day 2 in nontreated SAH rabbits (Control) was 35% compared with 21, 5, and 14% in rabbits treated with a total of 3 (Group A; n = 9), 6 (Group B; n = 13), and 9 mg (Group C; n = 5) of FUT-175, respectively. There were statistically significant differences in the arterial calibers between Group A and the Control on Days 1 and 2, between Group B and the Control from days 1 to 4, and between Group C and the Control from days 1 to 4. In three other rabbits, after vasospasm reached its maximum on Day 2, no vasodilatory effect was observed when a total of 6 mg of FUT 175 was administered intravenously. The results indicate that the inhibition of the plasma serine protease cascades at an early stage of SAH prevents the development of cerebral vasospasm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620298 TI - Therapeutic trial of cerebral vasospasm with the serine protease inhibitor, FUT 175, administered in the acute stage after subarachnoid hemorrhage. AB - The therapeutic effect of the synthetic serine protease inhibitor, FUT-175, on cerebral vasospasm after subarachnoid hemorrhage (SAH) was investigated. Twenty three patients with severe SAH who were admitted between February and July 1990 and who underwent surgery within 48 hours of the initial aneurysmal rupture were treated with an intravenous administration of FUT-175 soon after the operation. The patients were divided randomly into three groups, each receiving a different dose of FUT-175 (Group A, 20 mg every 12 hours for 4 days; Group B, 20 mg every 6 hours for 4 days, Group C, 40 mg every 6 hours for 4 days). The results were compared with another group of twenty-two patients with severe SAH who were admitted before February 1990 and received equivalent treatment, except they were not treated with FUT-175. In 64% of all the patients treated with FUT-175 (Groups A, B, C), and in 85% of those treated with higher doses of FUT-175 (Groups B and C), there was no spasm or only mild vasospasm on the angiogram. The incidence of a delayed ischemic neurological deficit significantly decreased from 55% in the control group to 13% in all patients treated with FUT-175 and to 7% in the patients treated with higher doses (P less than 0.05). The incidence of cerebral infarction resulting from vasospasm significantly decreased from 43% in the control group to 9% in patients treated with FUT-175. In the patients treated with higher doses of FUT-175 (Groups B and C), none developed cerebral infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620299 TI - Reconstruction of peripheral nerves: the phenomenon of bilateral reinnervation of muscles originally innervated by unilateral motoneurons. AB - It is well known that after reconstruction of sectioned peripheral nerves in adult mammals, denervated muscles are reinnervated by the axotomized motoneurons lying in the original motonucleus. It is less well known that these muscles can also be reinnervated by uninjured motoneurons lying in the homologous contralateral motonucleus. Therefore, after nerve reconstruction, bilateral motoneuron reinnervation of muscles can occur. Contralateral motoneurons sprout axons that cross the midline, grow in the reconstructed nerve, and reach muscle targets. This phenomenon was observed after reconstruction of several different peripheral nerves in adult mammals, including the oculomotor nerve in guinea pigs and the facial and sciatic nerves in rats. The retrograde axonal transport of horseradish peroxidase was used for the study of the organization of the brainstem and spinal cord motonuclei. Horseradish peroxidase was injected into the medial rectus muscle, the stylohyoid muscle, and the trunk of the sciatic nerve. The distance between the homologous motonuclei of both sides influenced the occurrence of this phenomenon. In fact, bilateral reinnervation of muscles after nerve reconstruction was found in 36% (sciatic nerve), 50% (facial nerve), and 100% (oculomotor nerve) of the operated animals. The total number of contralateral motoneurons found were 14% (oculomotor nerve), 8% (facial nerve), and 5% (sciatic nerve). Bilateral reinnervation of muscles was evoked by both immediate and delayed peripheral nerve repair and was a stable phenomenon, seen between 3 and 21 months after facial nerve reconstruction. PMID- 1620300 TI - Computed tomography and cerebral blood flow correlations of mental changes in chronic subdural hematoma. AB - To elucidate the pathophysiology of mental disturbances associated with chronic subdural hematoma, we performed quantitative and three-dimensional measurements of cerebral blood flow (CBF) on xenon-enhanced computed tomographic scans in 12 patients who had chronic subdural hematomas and manifested mental disturbances. In 2 patients who had no headache or hemiparesis, minimal mass effect, and severe multiple infarctions on computed tomographic scan, mentation did not improve after surgery. The CBF reduction was severe, and it further deteriorated after surgery. On the other hand, mentation improved to a varied extent in the other 10 patients, who had headache and/or hemiparesis and minimal, moderate, or severe mass effect and minimal or moderate multiple infarctions on computed tomographic scan. The CBF reduction was diffuse on both sides, but was more marked in the thalamus and putamen than it was in the cortex and subcortex. It was restored after surgery, but insufficiently. The restoration rate was statistically significant only in the thalamus, on both sides (with and without hematoma) (P less than 0.05). Dementia scores and CBF values after surgery were correlated on the side with the hematoma in the frontal cortex and thalamus (P less than 0.01) and in the hemisphere and temporoparietal cortex (P less than 0.05). There was no correlation on the side with the hematoma in the occipital cortex, putamen, and frontal and temporoparieto-occipital subcortices or on the side without the hematoma. The thalamus undergoes displacement and distortion by the hematoma, which in turn leads to changes in consciousness. Postoperative residual mental deficits consist primarily of dementia related to preexisting multiple infarctions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620301 TI - Translamino-pedicular screw fixation with bone grafting for symptomatic isthmic lumbar spondylolysis. AB - Anterior or posterolateral spondylodesis has been reported and used widely as a surgical treatment for lumbar spondylolysis or spondylolisthesis. Although spinal fusion is necessary when there is extensive vertebral slippage or spinal instability, the direct repair of the defect is thought to be anatomical, logical, and less invasive as a surgical treatment for symptomatic lumbar spondylolysis or a minimal degree of spondylolisthesis. This operation, with a few modifications, has been performed since 1985 in our clinic. The results, using Henderson's criteria, were excellent in 64.5% and good in 25.8% of the patients thus treated. For younger patients with symptomatic lumbar spondylolysis, direct repair of the defect using translamino-pedicular instrumentation with bone grafting is recommended, as degenerative changes have not usually occurred in the vertebral discs. PMID- 1620302 TI - Pediatric spinal cord and vertebral column injury. AB - Between January 1, 1970, and December 31, 1988, 179 children (birth to age 16) were treated for spinal cord and/or vertebral column injury by the Neurosurgical Service at the University of Iowa Hospitals and Clinics. Pediatric injuries accounted for 9% of all spinal trauma seen during this period. The mean age was 10.2 years. Sixty-two children were between birth and 8 years of age and 117 were between ages 9 and 16. The cause, distribution, type of injury, and severity of neurological injury varied with age. Neurological outcome was dependent on the severity of the initial neurological injury. Children with complete or severe incomplete myelopathy uniformly remained with severe neurological dysfunction; children with mild to moderate injuries recovered normal or nearly normal neurological function. Surgical versus nonoperative management had no bearing on neurological outcome. Twelve percent of the children with severe spinal cord injuries developed posttraumatic spinal deformity. We conclude that spinal injury patterns differ between preadolescent and older children. Most injuries can be successfully managed with nonoperative therapy. Prognosis is primarily correlated with the severity of the initial neurological insult. Finally, children with severe spinal cord injury must have close, long-term follow-up to monitor the development of posttraumatic spinal deformity. PMID- 1620303 TI - Optic nerve decompression surgery improves visual function in patients with pseudotumor cerebri. AB - Papilledema from pseudotumor cerebri can cause severe loss of visual acuity and visual field. We performed optic nerve decompression surgery on 17 patients with pseudotumor cerebri who, despite maximum conventional therapy, developed progressive loss of visual acuity and/or visual field. Postoperatively, visual acuity improved or stabilized in 33 of 34 eyes (97%). Visual fields improved in 20 of 21 eyes that underwent surgery. Optic nerve decompression surgery relieves local cerebrospinal fluid pressure on the optic nerve. Progressive loss of visual function associated with pseudotumor cerebri can be reversed or stabilized with optic nerve sheath decompression surgery. PMID- 1620304 TI - Experimental evaluation of a collagen-coated vicryl mesh as a dural substitute. AB - Dural substitutes must provide immediate restitution of a membranous covering for the brain without inducing any adverse reaction in the host or provoking adhesions to underlying nervous tissues. Ideally, the material should disappear completely and be replaced by tissues similar to the dura mater. In this study, parietal dural defects were created in 12 beagle dogs and closed with a vicryl mesh prosthesis made watertight by a film of bovine collagen. Clinical and biological tolerances were satisfactory. There was one case of early local infection. Gross and microscopic examinations performed between 7 days and 9 months after implantation showed degradation of the prosthetic mesh and connective tissue growth into the implant mimicking dura mater as early as 15 days after implantation. There was no attendant inflammatory reaction or cortical adhesions or other adverse reactions. The authors conclude that collagen-embedded vicryl mesh provides satisfactory biological function and compatibility when used as a substitute for dura mater in the dog. PMID- 1620305 TI - A comparison between magnetic resonance imaging and computed tomography for stereotactic coordinate determination. AB - The spatial accuracy of magnetic resonance imaging (MRI) has not been established for stereotactic surgery. Magnetic susceptibility artifacts may lead to anatomical distortion and inaccurate stereotactic MRI coordinates, especially when targets are in regions of the brain out of the center of the magnetic field. MRI-guided stereotactic localization, however, provides better multiplanar target resolution than is available with computed tomographic (CT) scanning. Therefore, we compared the accuracy of stereotactic coordinates determined by MRI and CT studies in 41 patients (53 targets). Coordinates were measured in each plane and as vector distances between the target and the center of the stereotactic frame on axial or coronal MRI studies. Absolute axial plane MRI and CT distances varied an average of 2.13 +/- 1.59 mm. The mean difference in measurements in the X (left-right) dimension was 1.19 mm and 1.55 mm in the Y (anterior-posterior) dimension. Central targets (located less than 2 cm from the frame center) had a mean MRI-CT difference of 2.09 +/- 1.79 mm; peripheral targets (greater than 2 cm from the frame center) differed by 2.17 +/- 1.3 mm. The voxel volumes were calculated for all compared images. Although differences between the physical properties of data acquisition with each imaging modality could explain the observed CT-MRI discrepancies, a 1-pixel difference in target selection could account totally for all the variance observed. MRI field strength (0.5 vs. 1.5 T) did not correlate with coordinate determination accuracy. We conclude that MRI guided stereotactic localization can be used with confidence for most diagnostic, functional, and therapeutic stereotactic procedures. PMID- 1620306 TI - Stereotactic, angiography-guided clipping of a distal, mycotic intracranial aneurysm using the Cosman-Roberts-Wells system: technical note. AB - We describe the use of stereotactic, angiographic guidance for localization and clipping of a small, distal intracranial bacterial aneurysm. The technique uses the commercially available Suetens-Gybels-Vandermeulen angiographic localizer with the widely used Cosman-Roberts-Wells stereotactic system. This method is simple and easy to use and significantly decreased the operative time. It may be quite useful for surgically treating mycotic and other peripheral aneurysms. PMID- 1620307 TI - Cauda equina syndrome secondary to an improperly placed nucleotome probe. AB - Automated percutaneous lumbar discectomy has been shown to be a low morbidity procedure in the treatment of contained herniated lumbar discs. Described in this paper is a complication, i.e., a cauda equina syndrome secondary to a Nucleotome probe improperly placed in the thecal sac. The authors reemphasize the landmarks for the thecal sac, i.e., the medial border of the pedicles, and discuss the preventable nature of this type of complication. PMID- 1620309 TI - Reversible arteriovenous malformation-induced venous hypertension as a cause of neurological deficits. AB - A case of a dural arteriovenous malformation with prominent localizing neurological deficits is reported. The venous drainage of the lesion and the lack of a significant pial supply implicate venous hypertension as the mechanism of neurological dysfunction. This mechanism is supported further by the angiographic changes and the prompt resolution of the deficits after endovascular treatment. This case illustrates the potential for this frequently postulated but rarely confirmed pathophysiological mechanism to cause reversible neurological dysfunction. PMID- 1620308 TI - Lichen simplex chronicus as the initial manifestation of intramedullary neoplasm and syringomyelia. AB - Neurogenic causes of pruritus and a rash are uncommon. We report a patient with dermatomal pruritus and a rash who had a cervicothoracic syrinx and a thoracic spinal cord tumor. We believe the syrinx interrupted fibers subserving itch, resulting in dermatomal pruritus with secondary scratching and a rash. PMID- 1620310 TI - Osteomyelitis of the skull base. AB - Three cases of osteomyelitis of the skull base with associated problems in diagnosis and therapy are discussed. Patients with atypical skull base osteomyelitis are difficult to diagnose as they have no ear abnormalities, but they often develop multiple cranial nerve deficits mimicking symptoms of a posterior fossa mass. We conclude that computed tomographic scans, magnetic resonance imaging studies, bone scans indium-labeled white blood cell scans, and gallium scans are useful in making the diagnosis. A biopsy of the bony lesion often is needed to identify the causative organism and to rule out a tumor. Intravenously administered antibiotics are the mainstay of therapy and should be continued until 1 week after the gallium scan shows no abnormalities. Follow-up gallium scans then are done at 1 week and 3 months after the cessation of antibiotic therapy to search for a recurrence. PMID- 1620311 TI - Benign intracerebral cysts treated with internal shunts: review and report of two patients. AB - Two elderly women with symptomatic benign intracerebral cysts are reported. Before treatment, they both had developed moderate, but slowly increasing, symptoms from a cyst in the left hemisphere, which included epileptic seizures and right hemiparesis. During local anesthesia, an internal cystosubarachnoid shunt was inserted. After the operation, the cyst size was reduced markedly, with a corresponding improvement in the symptoms. A review of reported cases of benign intracerebral cysts is given. The average age of these patients is surprisingly high for a presumed congenital condition. There is a female preponderance, but the previously reported overrepresentation of left-sided lesions is not found in cases described after the introduction of computerized tomographic imaging. PMID- 1620312 TI - Multiple cerebral hydatid disease: case report with magnetic resonance imaging study. AB - A case of multiple hydatid cysts of the brain is reported. Computed tomographic and magnetic resonance imaging scanning revealed a thick and calcified pericystium. These findings allowed appropriate surgical planning, with a marked recovery of the neurological deficits and absence of relapse in the follow-up period. PMID- 1620313 TI - Meningioma and sagittal craniosynostosis in an infant: case report. AB - The occurrence of a frontal base meningioma in a 3-month-old infant seen for the treatment of sagittal craniosynostosis is reported. The association of the two lesions is of interest both because it is unique and may lend support to theories of the cause of some forms of craniosynostosis. PMID- 1620314 TI - The radiological differentiation of acoustic neurinoma and meningioma occurring together in the cerebellopontine angle. AB - A patient with right hearing loss, in whom computed tomographic scanning demonstrated a mass in the right cerebellopontine angle with widening of and extension into the internal auditory canal, but with important posterior extension and broad implantation on the surface of the petrous bone, is reported. On both T2-weighted and gadolinium-enhanced T1-weighted magnetic resonance images, there were clearly two separate tumoral lesions: an acoustic neurinoma extending into the internal auditory canal and a meningioma with broad implantation on the petrous apex. These findings were confirmed at surgery. PMID- 1620315 TI - Meningeal hemangiopericytoma of the posterior fossa and thoracic spinal epidural space: case report. AB - The rare combination of spinal and intracranial meningeal hemangiopericytomas in the same patient is reported. The coexistence of cerebral and spinal meningiomas of all histological subtypes is distinctly uncommon with only nine cases found in the literature. PMID- 1620317 TI - Craniopharyngioma of the posterior fossa. PMID- 1620318 TI - Cyst of the ligamentum flavum: report of six cases. PMID- 1620316 TI - Informed consent: is it a myth? AB - The issue of informed consent at it relates to neurosurgical professional malpractice liability and litigation has been of concern for 20 years or more. The problem persists, and the subject has been addressed by providing patient education with full disclosure regarding neurosurgical procedures. In the process of imparting informed consent, the authors studied the effectiveness of specific neurosurgical health care teaching. One hundred six persons undergoing anterior cervical fusion or lumbar laminectomy were instructed by a neurosurgeon and clinical nurse specialist with a master's degree in neurosurgery. Written testing was performed in each case immediately after a formal teaching session before surgery. Questions were simple and covered only four general topics: 1) diagnosis and surgical techniques; 2) operative risks; 3) postoperative care; and 4) goals and benefits relating to surgery. The mean score on testing immediate retention of information revealed a 43.5% overall performance rate. When patients were tested approximately 6 weeks later, the score dropped to 38.4%. This was statistically significant (chi 2, P less than 0.05). The authors encourage the concept of patient education. The data in the current study, however, suggest that the reasonable and prudent neurosurgeon making a concerted effort at patient education, with the assistance of a professional educator, cannot necessarily expect accurate patient or family recall or comprehension. Fulfillment of the doctrine of informed consent by neurosurgeons may very well be mythical. PMID- 1620319 TI - Functional recovery after traumatic transtentorial herniation. PMID- 1620320 TI - Spinal man after declaration of brain death. PMID- 1620321 TI - Levels of processing for visual stimuli in an "extinguished" field. AB - Volpe et al. (Nature 282, 722, 1979 [19]) described an experimental study of four patients with parietal tumours who were able to judge whether two simultaneous stimuli were identical or different, even when they were unable to name the stimulus contralateral to their brain injury. We report the case of another patient, E.M., in whom we have investigated this phenomenon further. E.M. had undergone a right temporal lobectomy to prevent recurrent seizures. She could correctly name photographs of objects presented in isolation to either the left or right visual field, at 150 msec exposure (although she was impaired for single objects on the left at 10 msec exposures). She was able to judge correctly whether two simultaneous objects on the left and right had the same or different names, even though she was often unable to name the object on the left. These judgements remained above chance when same-name pairs of stimuli showed the same object but seen from two different viewpoints, or even when they showed visually dissimilar exemplars of the same name category. This implies that the patient based her same-different judgements on categorical information about the pair of objects, even though she was often unable to name the contralateral object. PMID- 1620322 TI - Investigation of the role of sex hormones in alcoholics' visuospatial deficits. AB - This study investigated whether an alcohol-related disturbance in the functioning of the hypothalamic-pituitary-gonadal axis was a factor in alcoholics' visuospatial impairment. One month detoxified male alcoholics (n = 58) performed significantly poorer than peer controls (n = 30) on a battery of visuospatial and verbal tests. Serum concentrations of testosterone, estradiol, luteinizing hormone and follicle stimulating hormone were obtained at three times during cognitive testing. Previously reported correlations in healthy young male adults between visuospatial performance with testosterone and follicle stimulating hormone concentrations were replicated in control subjects. These correlations were not significant in the alcoholics. The results suggest that chronic alcoholism may disrupt the normal relationships between the hypothalamic pituitary-gonadal axis and cognitive functioning. PMID- 1620323 TI - Delayed matching to sample and concurrent learning in nonamnesic humans with alcohol dependence. AB - Small samples of alcohol-dependent subjects who showed no clinical signs of Wernicke-Korsakoff syndrome were compared with nonalcohol-dependent controls on two animal memory tests which are performed poorly by human amnesics. Compared to the control subjects, the alcohol-dependent subjects' performance was impaired on a version of the delayed matching to sample task. On concurrent discrimination learning the overall group difference just failed to reach significance. The results are interpreted as suggesting that behavioural impairment may occur in alcohol-dependent subjects who are not clinically amnesic, and that the impairment is similar in type to that observed in cases of severe Wernicke Korsakoff syndrome. PMID- 1620324 TI - A re-appraisal of a case of persistent global amnesia following right temporal lobectomy: a clinico-pathological study. AB - We report a reappraisal of patient NT who became severely amnesic after a right temporal lobectomy for intractable epilepsy (DINSDALE et al., Neuropsychologia 1, 287, 1964 [6]). Histological examination, albeit incomplete, indicated that there was no abnormality in the resected temporal lobe. At autopsy a sclerotic lesion of the unoperated left hippocampal formation was found. This case is therefore not an exception to the general rule that a severe and global amnesic state is only observed with bilateral lesions. Her performance on a wide range of memory tests is shown to be indistinguishable from patients with an amnesic syndrome due to Korsakoff's psychosis. PMID- 1620325 TI - Verbal learning and memory in language impaired children. AB - The present study investigated patterns of verbal learning and memory in Language Impaired (LI) and normal children, using the California Verbal Learning Test- Children's Version. The LI children showed a normal immediate memory span; however, they were impaired in the total number of correct responses that they generated across repeated trials. They reported significantly more perseverations, but not intrusions, relative to the controls. The LI children were not impaired on a delayed free recall task, but they were significantly impaired relative to the controls on semantically cued recall. The implications of these findings for future research and for remediation are discussed. PMID- 1620326 TI - Are specific reading and writing difficulties causally connected with developmental spatial inability? Evidence from two cases of developmental agnosia and apraxia. AB - Two cases studies of subjects suffering from severe developmental constructional apraxia are presented. These two subjects demonstrated normal to high ability in reading, writing and arithmetical tests. The analysis of cognitive tests performed by them indicates that extreme developmental, perceptual, spatial and motor deficits may be dissociated from the acquisition of efficient reading ability. PMID- 1620327 TI - Pathological left-handedness revisited: dichotic listening in children with left vs right congenital hemiplegia. AB - Thirty-one children with right (n = 18) and left (n = 13) congenital hemiplegia were compared for incidence of hand- and foot-preference, eye-dominance, and familial sinistrality. In addition, they were tested with dichotic listening for correct reports of consonant-vowel syllables. The two groups of children were closely matched on IQ and sensory functioning. Children with mental retardation, or epileptic seizures were not included. The results showed that 89% of the left hemisphere impaired (LHI) children were left-handed, all of them preferred the left foot, and 72% were left eye-dominant. In the right hemisphere impaired (RHI) group, everyone (100%) preferred the right hand and foot, and 62% were right eye dominant. The dichotic listening results showed a significant right ear advantage (REA) in the RHI-group, and a significant left ear advantage (LEA) in the LHI group. The results are discussed in the framework of pathological handedness and shifts in hemisphere control of language in children with early brain injury. It is argued that the homogeneous samples, except for the site of lesion, provides an interesting possibility to compare cognitive effects of left and right hemisphere impairment in children. PMID- 1620328 TI - Hand preference, prematurity and developmental outcome at school age. AB - Information was obtained on the hand preference of 88 premature and 80 matched full-term children at 7-8 years old. These children were also evaluated for neurologic status, IQ, attention-deficit hyperactivity disorder, and learning disabilities. Although the difference on hand preference was not significant, 12% more of the premature children than the full-term children were left- or mixed handed. Results showed that, among premature children, there is an association between non-right-handedness and cognitive and behavioral deficits and that left handed children show relative clumsiness with the non-preferred hand. PMID- 1620329 TI - Memory impairment and depression in patients with Lyme encephalopathy: comparison with fibromyalgia and nonpsychotically depressed patients. AB - Lyme encephalopathy, primarily manifested by disturbances in memory, mood, and sleep, is a common late neurologic manifestation of Lyme disease. We compared 20 patients with Lyme encephalopathy with 11 fibromyalgia patients and 11 nonpsychotically depressed patients using the California Verbal Learning Test, Wechsler Memory Scale, Rey-Osterrieth Complex Figure Test, Minnesota Multiphasic Personality Inventory (MMPI), and Beck Depression Inventory. Compared with patients with fibromyalgia or depression, the Lyme encephalopathy group showed mild, but statistically significant, memory deficits on two of the three memory tests. In contrast, the patients with fibromyalgia scored significantly higher than both other groups on the MMPI scale most sensitive to somatic concerns (scale 1), while the depressed patients scored higher than the Lyme patients on the scales most sensitive to depression (scale 2) and anxiety (scale 7). Physical complaints and depression were not major factors in memory performance among Lyme patients. These data support the hypothesis that Lyme encephalopathy is caused by CNS dysfunction and cannot be explained as a psychological response to chronic illness. PMID- 1620330 TI - Lyme borreliosis in Bell's palsy. Long Island Neuroborreliosis Collaborative Study Group. AB - Lyme borreliosis (LB) causes a range of neurologic manifestations, the most common of which is facial nerve paralysis. To evaluate nervous system LB, we organized a neurologic collaborative study group in Suffolk County, NY, a region of high LB incidence. Between July and September 1989, LB serologies were performed on all patients with new-onset Bell's palsy. Seven of 32 had serologic evidence of LB at onset. One, initially seronegative, was highly seropositive 5 weeks later. In the five in whom we examined CSF, there was no evidence of intrathecal synthesis of specific antibody. In highly endemic areas, LB may be responsible for 1/4 of cases of Bell's palsy. Rarely, the palsy may occur prior to the development of a measurable antibody response, indicating a need for follow-up serologic testing. PMID- 1620331 TI - Pupillary escape. AB - I performed a pupillographic study of pupillary escape to determine its effectiveness in detecting optic nerve and retinal disease. Fourteen patients and 39 normal subjects were included in the study. Only one patient had abnormal pupillary escape, even though 13 patients had relative afferent pupillary defects. Testing for pupillary escape is not a reliable clinical technique. PMID- 1620332 TI - Frontal lobe partial seizures and psychogenic seizures: comparison of clinical and ictal characteristics. AB - Of all partial seizures, those of frontal lobe origin (FLPS) are most bizarre and are often mistaken for psychogenic seizures (PS). The reverse can also be true. To clarify the confusing clinical presentation of these different seizure types, we compared the clinical ictal characteristics of 63 FLPS in 11 patients with 29 PS in 12 patients. Patients with PS had significantly later age at onset and longer ictal duration. There was no statistically significant difference between the two groups with respect to history of psychiatric disorder, ictal pelvic thrusting, rocking of body, side-to-side head movements, or rapid postictal recovery, all of which previously have been reported as characteristic features of PS. Turning to a prone position during the seizure occurred only in FLPS. Nocturnal occurrence, short ictal duration, younger age at onset, stereotyped patterns of movements, and MRI and EEG abnormality suggested FLPS. PMID- 1620333 TI - Seizures in children with congenital hydrocephalus: long-term outcome. AB - We documented seizures in 33 of 68 (48.5%) children with congenital hydrocephalus not associated with myelomeningocele. Mental retardation (MR) and CNS malformations correlated with seizure occurrence; age at shunt insertion and number of shunt revisions and infections were not significant variables in predicting seizures. Of 11 patients seizure free for 2 or more years on medication, six had therapy discontinued without seizure recurrence. Among those 33 children with seizures, 14 (42.4%), including five who had failed withdrawal of medication, have adequately controlled seizures on anticonvulsants. Frequent convulsions despite treatment occur in 13 (39.4%) of the 33 children with seizures. Absence of MR, older age and nonparoxysmal EEG at seizure onset, and absence of CNS malformation correlated with seizure remission. Longer time without seizures while on medication did not predict successful discontinuation of therapy. In contrast, MR correlated significantly with seizure recurrence following cessation of treatment. Our study indicates that medication can be safely discontinued in children with congenital hydrocephalus who are of normal intelligence and have been seizure free on anticonvulsants for 3 years. PMID- 1620334 TI - Syphilitic cerebral gumma with HIV infection. AB - We describe two human immunodeficiency virus (HIV)-infected patients with syphilitic cerebral gummas. Both patients presented with a seizure disorder associated with an isolated, peripherally located, contrast-enhancing lesion of the brain on CT. Cranial MRI performed on one patient revealed dural thickening in the region of the lesion. A brain biopsy in that patient revealed a lymphoplasmacytic infiltrate with extensive perivascular inflammation. Clinical manifestations, radiographic resolution of the lesions, and a decline in nontreponemal serologic tests for syphilis followed high-dose aqueous penicillin therapy in both patients. These patients illustrate that (1) cerebral mass lesions occurring with HIV infection may result from syphilis; (2) seizures may be the presenting manifestation of this form of neurosyphilis; and (3) high-dose, intravenous, aqueous penicillin is effective in treating these lesions. PMID- 1620335 TI - Time interval between repeated injections conditions the duration of motor improvement to apomorphine in Parkinson's disease. AB - Behavioral hyposensitivity to repeated apomorphine administration occurs in fluctuating parkinsonian patients. To determine to what extent the interval between doses influences the response, we administered equal paired apomorphine injections to 10 fluctuating parkinsonian patients. Subjects received two apomorphine injections at 2-hour and at 4-hour intervals on different days after a 10- to 12-hour overnight period without levodopa. Following apomorphine doses at 2-hour intervals, the duration of response was reduced by 40% (61 versus 42 minutes, p less than 0.001) but was of equal duration when the doses were given at 4-hour intervals. These findings indicate that the interval between doses is a critical determinant of motor response. We postulate a time-dependent period of partial hyposensitivity to pulsatile DA stimulation. PMID- 1620336 TI - Neuropsychological and structural brain lesions in multiple sclerosis: a regional analysis. AB - Quantified lesion scores derived from MRI correlate significantly with neuropsychological testing in patients with multiple sclerosis (MS). Variables used to reflect disease severity include total lesion area (TLA), ventricular brain ratio, and size of the corpus callosum. We used these general measures of cerebral lesion involvement as well as specific ratings of lesion involvement by frontal, temporal, and parieto-occipital regions to quantify the topographic distribution of lesions and consequent effects upon cognitive function. Lesions were heavily distributed in the parieto-occipital regions bilaterally. Neuropsychological tests were highly related to all generalized measures of cerebral involvement, with TLA being the best predictor of neuropsychological deficit. Mean TLA for the cognitively impaired group was 28.30 cm2 versus 7.41 cm2 for the cognitively intact group (p less than 0.0001). Multiple regression analyses revealed that left frontal lobe involvement best predicted impaired abstract problem solving, memory, and word fluency. Left parieto-occipital lesion involvement best predicted deficits in verbal learning and complex visual integrative skills. Analysis of regional cerebral lesion load may assist in understanding the particular pattern and course of cognitive deficits in MS. PMID- 1620337 TI - The diagnostic reliability of magnetically evoked motor potentials in multiple sclerosis. AB - In a prospective study, we evaluated the technique of magnetically evoked motor potentials (MEP) in the diagnosis of multiple sclerosis (MS). We consecutively included 68 patients with symptoms or signs compatible with a demyelinative CNS affection. We subjected all patients to CSF analysis, MRI studies of the brain and brainstem, visual evoked potentials (VEP), brainstem auditory evoked potentials (BAEP), and somatosensory evoked potentials (SSEP). We then used the results to categorize the patients according to the Poser criteria of multiple sclerosis. Blinded from the results of the above investigations, one of the authors made MEP recordings from three muscles in the upper limbs and two in the lower limbs in all 68 patients. Forty patients received an MS diagnosis, and in these, MRI was positive in 88%, MEP in 83%, VEP in 67%, SSEP in 63%, and BAEP in 42%. As to the diagnosis of MS, the reliability of a prolonged central motor conduction time (CMCT) was 0.83 (0.73 to 0.93), while the reliability of a normal CMCT was 0.75 (0.61 to 0.98). The information gained by MRI was best supplemented by VEP. Of the neurophysiologic tests, the MEP was in closest agreement with the MRI with a concordance of 85%. PMID- 1620338 TI - Rapid reversible modulation of human motor outputs after transient deafferentation of the forearm: a study with transcranial magnetic stimulation. AB - Reorganization of corticospinal pathways after spinal cord injury and amputations leads to increased excitability of motor pathways targeting muscles proximal to the level of interruption of efferents from the CNS. To study the timing of these changes, we have recorded motor evoked potentials (MEPs) in the arm muscles of three normal subjects before, during, and after anesthetic block of the forearm and hand. The amplitudes of MEPs from biceps, which was the muscle immediately proximal to the block, gradually increased with anesthesia and then returned to preanesthesia levels within approximately 20 minutes after anesthesia was ended. MEPs from the contralateral arm were unaffected. Such rapid changes strongly suggest unmasking of preexisting synaptic connections, due to disinhibition at cortical or subcortical levels, as the mechanism underlying acute modulation of motor outputs. PMID- 1620339 TI - Dysphagia after botulinum toxin injections for spasmodic torticollis: clinical and radiologic findings. AB - We prospectively evaluated the frequency, severity, and radiologic features of swallowing abnormalities following Botox treatment of spasmodic torticollis. We performed both clinical and radiologic evaluations of swallowing before and following Botox in 18 consecutive cervical dystonia patients receiving their first Botox treatment. Before Botox, 11% of the patients had clinical symptoms of dysphagia and 22% had radiologic signs of a peristaltic abnormality. After Botox, the signs and symptoms of dysphagia in these patients did not change, but an additional 33% developed new dysphagic symptoms and 50% of the patients developed new peristaltic abnormalities by radiologic studies. Complaints of swallowing difficulty were always associated with abnormal radiologic findings. Neither the total Botox dose nor Botox into particular muscles differed between those with dysphagia and those without. PMID- 1620340 TI - Blinded evaluation confirms long-term asymmetric effect of unilateral thalamotomy or subthalamotomy on tremor in Parkinson's disease. AB - In the past, stereotactic surgery was a regular treatment for prominent unilateral tremor in Parkinson's disease (PD), but follow-up studies were usually short-term and always unblinded. We examined 17 PD patients in long-term follow up (mean, 10.9 years after surgery) and used videotapes and the Unified Parkinson's Disease Rating Scale to blindly compare tremor ipsilateral and contralateral to the side of surgery. Since the patients were specifically selected for stereotactic surgery because of asymmetric tremor, and the surgical side chosen was contralateral to the predominant tremor, a sign of long-term efficacy would be current postoperative reversal of tremor side predominance. Upper extremity tremor was significantly better contralateral to the surgery compared with the ipsilateral side. We conclude that stereotactic surgery improved the absolute magnitude of tremor or ameliorated its rate of progression. Since asymmetric bradykinesia and dyskinesia were not a prerequisite for the choice of surgical side, we cannot make any conclusion about long-term impact of surgery on these features. PMID- 1620341 TI - Levodopa-nonresponsive Lewy body parkinsonism: clinicopathologic study of two cases. AB - We report two patients with a primarily akinetic form of parkinsonism who were nonresponsive to treatment with levodopa. At autopsy, both patients had many Lewy bodies in brainstem and diencephalic nuclei, with sparse Lewy bodies in association cortices and more numerous Lewy bodies in the limbic cortices, consistent with the transitional form of Lewy body disease. These cases emphasize that (1) Lewy body Parkinson's disease cannot be excluded on the basis of atypical presentation or levodopa nonresponsiveness, and (2) the clinicopathologic spectrum of Lewy body disease is varied. PMID- 1620342 TI - Parkinson's disease and exposure to agricultural work and pesticide chemicals. AB - This population-based case-control study of 130 Calgary residents with neurologist-confirmed idiopathic Parkinson's disease (PD) and 260 randomly selected age- and sex-matched community controls attempted to determine whether agricultural work or the occupational use of pesticide chemicals is associated with an increased risk for PD. We obtained by personal interviews lifetime occupational histories, including chemical exposure data, and analyzed the data using conditional logistic regression for matched sets. In the univariate analysis, a history of field crop farming, grain farming, herbicide use, or insecticide use resulted in a significantly increased crude estimate of the PD risk, and the data suggested a dose-response relation between the PD risk and the cumulative lifetime exposure to field crop farming and to grain farming. However, in the multivariate analysis, which controlled for potential confounding or interaction between the exposure variables, previous occupational herbicide use was consistently the only significant predictor of PD risk. These results support the hypothesis that the occupational use of herbicides is associated with an increased risk for PD. PMID- 1620343 TI - Content of the neurotoxins cycasin (methylazoxymethanol beta-D-glucoside) and BMAA (beta-N-methylamino-L-alanine) in cycad flour prepared by Guam Chamorros. AB - Exposure to cycad seed kernel is an etiologic factor for the western Pacific amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC). Traditionally processed cycad flours (n = 17) obtained from Chamorro residents of Guam and the adjacent island of Rota at risk for neurodegenerative disease were extracted and analyzed by high-performance liquid chromatography for content of beta-N-methylamino-L-alanine (BMAA) and methyl-azoxymethanol beta-D-glucoside (cycasin). Cycasin (detection limit: picomole) was present in concentrations of 0.004 to 75.93 micrograms/g (mean, 12.45 +/- 5.0 micrograms/g), and levels of BMAA (detection limit: subpicomole) ranged from 0.00 to 18.39 micrograms/g (mean, 5.44 +/- 1.56 micrograms/g). On average, cycasin content was approximately 10 times higher than that of BMAA. The largest concentrations of cycasin were found in samples from villages with a high reported prevalence of ALS/PDC. Ingestion of cycad-derived food would result in estimated human exposure to milligram amounts of cycasin per day. The cytotoxic properties of cycasin merit consideration in relation to the etiology of western Pacific ALS/PDC. PMID- 1620344 TI - Borrelia burgdorferi and other related spirochetes bind to galactocerebroside. AB - Spirochetes are agents of neurologic disease that may utilize specific neural cell surface molecules for adhesion. Borrelia burgdorferi, the etiologic agent of Lyme disease, bound to galactocerebroside (GalCer) in numbers that were two- to threefold greater than to ceramide and glucocerebroside, and four- to fivefold greater than to sphingosine, psychosine, sulfatide, cholesterol, and three membrane phospholipids. The adherence was greater to GalCer and ceramide with a higher content of alpha-hydroxyl fatty acids. Treponema phagedenis Reiter and Borrelia hermsii also bound to GalCer. The binding of B burgdorferi to GalCer was inhibited in a concentration-dependent manner by rabbit polyclonal and murine monoclonal antibodies to this glycosphingolipid component of myelin. The monoclonal antibody to GalCer also inhibited adhesion of the organisms to Schwann cells. Neither free D or L monosaccharides nor the lectin peanut agglutinin inhibited binding. Since B burgdorferi and other spirochetes cause neurologic disease, these results suggest a role for GalCer as a binding site in both the central and peripheral nervous systems. PMID- 1620345 TI - Spectroscopic imaging of stroke in humans: histopathology correlates of spectral changes. AB - Previous studies of human stroke by 1H nuclear magnetic resonance spectroscopy have shown elevation of lactate lasting 3 to 6 months. Complete metabolic turnover of the elevated lactate pool has been demonstrated 5 weeks after a stroke. Its cellular localization is among the first questions requiring clarification. Information pertinent to this question came to us from a patient with a 2-week-old stroke by 1H nuclear magnetic resonance spectroscopic imaging 1 week before his death led to neuropathologic examination of the brain. 1H spectra from voxels including the infarcts showed increased lactate and decreased N acetylaspartate. Histopathology showed sheets of foamy macrophages in the infarct, but few neurons. Macrophage density ranged from 196 cells/mm2 near the surface of the infarct to 788 near its medial margin. Glial density was 500 to 800 cells/mm2. Lactate concentration in voxels including portions of the infarct was estimated at 7 to 14 mM. Voxels showing low N-acetylaspartate and high lactate on spectroscopic imaging were associated with histopathologic sections containing foamy macrophages. Brain macrophages--which begin to appear 3 days after infarction and gradually disappear over several months--could be a major source of elevated lactate signals that persist for months after stroke. PMID- 1620346 TI - Protease nexin I, thrombin- and urokinase-inhibiting serpin, concentrated in normal human cerebrospinal fluid. AB - Protease nexin I (PNI), a 43,000- to 50,000-dalton glycoprotein, is a potent thrombin and urokinase inhibitor produced by many mammalian cells, including human glia, in tissue culture. PNI is a member of the growing superfamily of serine protease inhibitors now known as serpins, but, unlike many others of this family, it has not yet been detected in normal human plasma. Of interest to neurobiology and neurologic disease, PNI is identical to a glia-derived neurite promoting factor, glia-derived nexin (GDN). Antibody to PNI stains the periphery of senile amyloid plaques in brain tissue from patients with Alzheimer's disease (AD), along with another serpin, alpha 1-antichymotrypsin (alpha 1-ACT). A soluble form of the beta-amyloid precursor protein (beta APP), containing a Kunitz-type trypsin inhibitor domain, the beta APP751 form, is identical to protease nexin II (PNII), a 100,000-dalton serine protease inhibitor present in a number of tissues besides the brain. PNII/beta APP is also found in normal and AD CSF. We found a 47,000-dalton PNI, a thrombin- and urokinase-inhibiting serpin, in normal human CSF by Western blotting using a monospecific antibody. We also demonstrated biologically active PNI capable of forming complexes with serine proteases 125I-urokinase or 125I-thrombin. PMID- 1620347 TI - Dose response, coasting, and differential fiber vulnerability in human toxic neuropathy: a prospective study of pyridoxine neurotoxicity. AB - We administered either 1 or 3 g/d of pyridoxine (vitamin B6) to five healthy volunteers and repeatedly followed serum pyridoxal phosphate levels, clinical symptoms and signs, quantitative sensory thresholds (QSTs), and sural nerve electrophysiology. Pyridoxine was discontinued at the first sign of either clinical or laboratory abnormality. In all subjects, sensory symptoms and QST abnormalities occurred concurrently. Subjects receiving higher doses became symptomatic earlier than low-dose subjects. Elevation of thermal QSTs preceded or exceeded that for vibration in the three low-dose subjects; vibration and thermal QST became abnormal simultaneously in the higher-dose subjects. A reduction in the amplitude of the sural sensory potential lagged behind QST changes in two of three subjects. Symptoms continued to progress ("coasting") for 2 to 3 weeks despite stopping pyridoxine administration and the return of serum pyridoxal phosphate levels to normal. This study suggests that (1) there is a clear dose percent relationship for pyridoxine-induced neuropathy, (2) QST is a sensitive measurement for detecting early peripheral neuropathy; QST abnormalities may precede changes in nerve conduction studies, (3) coasting appears unrelated to persistently elevated blood levels of the toxin, and (4) a dose-dependent vulnerability may exist among nerve fibers of different caliber when exposed to an axonal toxin, such as pyridoxine. PMID- 1620348 TI - Polysomnographic features of REM sleep behavior disorder: development of a scoring method. AB - REM sleep behavior disorder (RBD) is characterized by the intermittent absence of REM sleep EMG atonia and the appearance of elaborate motor activity associated with dream mentation. There are no specific diagnostic criteria for RBD based upon polysomnographic findings. We describe a new scoring method and show its sensitivity to treatment with clonazepam. An increased phasic submental EMG density occurs in RBD patients, but REM density is similar to that of controls. Clonazepam selectively decreases REM sleep phasic activity but exerts no effect on REM sleep atonia. Periodic limb movements in sleep (PLMS) occur equally in both REM and NREM sleep in RBD patients, suggesting that normal suppression of PLMS in REM sleep is due to motor inhibition. PMID- 1620349 TI - Causal heterogeneity in isolated lissencephaly. AB - We report clinical, cytogenetic, and molecular studies in 65 patients with isolated lissencephaly sequence (ILS). All had type I lissencephaly of varying severity and a grossly normal cerebellum. Some had additional brain abnormalities. Facial appearance was essentially normal. All had severe to profound mental retardation, seizures, hypotonia that evolved into spasticity, and feeding difficulties. Clinical and laboratory studies demonstrated etiologic heterogeneity. Molecular studies detected microdeletions in chromosome band 17p13.3 in six of 44 patients tested, confirming that deletion of all or part of this "critical region" is the cause of ILS in some cases. There were slightly larger deletions in the same region in a majority of patients with Miller-Dieker syndrome. One patient had an apparently balanced, de novo reciprocal translocation with breakpoints at Xq22 and 2p25. Four sibs from two families had a new, autosomal recessive syndrome of ILS with neonatal death. Other causes supported by clinical observations include autosomal recessive inheritance, intrauterine infection, and intrauterine perfusion failure. Those ILS probands in whom no etiology could be established had 41 sibs of whom three were affected, giving an empiric recurrence risk of 7%. PMID- 1620350 TI - Rate and types of fractures in corticosteroid-treated multiple sclerosis patients. AB - In a retrospective study of 103 corticosteroid-treated MS patients, the average rate of fracture events was 3.2% of the patients per year over 7.1 (+/- 5.7 SD) years at risk. Fractures of the ribs, pelvis, hip, or vertebrae occurred in 11 patients and became most common 5 years after starting steroids. Relatively high or low cumulative doses of steroids did not correlate predictably with the occurrence of fractures. PMID- 1620351 TI - Botulinum toxin treatment of supranuclear ocular motility disorders. AB - We treated one patient with bilateral internuclear ophthalmoplegia and another with skew deviation with extraocular muscle botulinum toxin injection. Both patients had pre-injection symptomatic diplopia in primary position, one for 1 month and the other for 12 months. Resolution of diplopia and complete and permanent binocular fusion in primary position was obtained within 3 to 4 days in both cases. PMID- 1620352 TI - The effect of acetazolamide on essential tremor: an open-label trial. AB - We studied the effect of the carbonic anhydrase inhibitor acetazolamide on 24 patients with essential tremor by patient self-evaluation of functional disability, rating of motor task function, and clinical rating of tremor severity. Acetazolamide significantly reduced tremor severity, but there was no statistically significant change in patient self-assessment of function or motor task rating. Although side effects were common, over half the patients elected to remain on the drug. PMID- 1620353 TI - Familial cluster headache: occurrence in three generations. AB - We report the occurrence of cluster headache in three generations of one family: an 8-year-old boy with primary chronic cluster headache, his 42-year-old father with secondary chronic cluster headache, and his 73-year-old paternal grandfather with episodic cluster headache. PMID- 1620354 TI - Hair loss after prolonged EEG/video monitoring. AB - We report five patients who experienced delayed patchy hair loss after prolonged EEG monitoring. The location of the patches corresponded to the electrode sites in four. The hair loss was temporary and most probably was due to traumatic noncicatricial alopecia. The frequency of hair loss was approximately 2% of monitored patients. PMID- 1620355 TI - Memantine prevents HIV coat protein-induced neuronal injury in vitro. AB - Studies with in vitro model systems suggest that at least part of the neurologic deficits of human immunodeficiency virus (HIV)-1-associated cognitive/motor complex may stem from neuronal injury mediated by the HIV-1 coat protein gp120. Concurrent activation of N-methyl-D-aspartate (NMDA) receptors is also necessary for gp120 to induce neuronal damage. We studied memantine, a drug that blocks NMDA receptor-operated ion channels, for possible protective effects from gp120 induced neuronal injury. In identified rat retinal ganglion cells in culture, we found that 2 microM memantine completely prevented the injury engendered by 20 pM gp120. These data suggest that memantine has therapeutic potential as an NMDA antagonist capable of ameliorating neuronal damage associated with gp120. PMID- 1620357 TI - Report of the MDA Gene Therapy Conference, Tucson, Arizona, September 27-28, 1991. AB - C. Thomas Caskey, in summarizing the meeting, noted that phenotypic correction of DMD is likely to require restoration of the dystrophin protein; thus, this disease is a logical target for consideration of gene replacement therapy. A number of tools are available to the experimenter, including the dystrophin gene and cDNA, several viral vectors, and various animal models of the human disease. In addition, detailed knowledge is now becoming available about the mechanisms of muscle-specific gene expression. However, a number of uncertainties have yet to be resolved. The dystrophin gene has an extremely complex pattern of expression, with more than one promoter and a number of alternative splicing events; what are the reasons for this variety? The dystrophin-glycoprotein complex has been described but its function is unclear. The role of the satellite cell is uncertain. It is not yet clear whether viral delivery or direct injection of DNA will be the method of choice for gene transfer into muscle. If delivery methods do not target the appropriate tissues, then appropriate use of tissue-specific control elements will be required for selective gene expression. Which animal model system should be used? What role can myoblast transplantation (with or without gene transfer) play in the treatment of DMD and other inherited myopathies? It is hoped that in further meetings on this topic, some of these issues will have been resolved. PMID- 1620356 TI - Clinical and neuroradiologic findings of congenital hydrocephalus in infant born to mother with HTLV-I-associated myelopathy. AB - We describe clinical and neuroradiologic findings in a male infant with congenital hydrocephalus born to a mother who developed human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy. Ultrasonography at age 20 days showed multiple cysts in the subependymal germinal matrix and enlarged lateral ventricles. Elevation of serum HTLV-I antibody suggested that his hydrocephalus was probably due to intrauterine HTLV-I infection. HTLV-I may cause neurotropic infection in utero. PMID- 1620358 TI - Thoracic aortic aneurysm presenting as paraparesis: a case report. PMID- 1620359 TI - Syringomyelia as a late complication of paralytic poliomyelitis. PMID- 1620360 TI - Clinical and electrophysiologic improvement in Lambert-Eaton syndrome with intravenous immunoglobulin therapy. PMID- 1620361 TI - Eosinophilic meningitis due to Angiostrongylus cantonensis. PMID- 1620362 TI - Paraneoplastic syndromes. PMID- 1620363 TI - Transcranial stimulation. PMID- 1620364 TI - Neurodegenerative disorders. PMID- 1620365 TI - Neurodegenerative disorders. PMID- 1620366 TI - Neurodegenerative disorders. PMID- 1620367 TI - Neurodegenerative disorders. PMID- 1620369 TI - Slit-like ventricles. PMID- 1620368 TI - Essential tremor. PMID- 1620370 TI - Anabolic steroids and muscular dystrophy. PMID- 1620371 TI - Diagnosing subarachnoid hemorrhage in the ED. PMID- 1620372 TI - Limb salvage in war. PMID- 1620373 TI - 1991 Federal Nursing Service Award recipient. The effect of increased atmospheric pressure on glucose reagent strip accuracy. AB - Hyperbaric oxygen (HBO) is currently being used throughout the world as an adjunctive therapy for non-healing diabetic wounds. Anecdotal accounts of diabetic patients experiencing hypoglycemic reactions with HBO necessitated glucose testing by fingerstick during treatment dives to 2.4 atmospheres absolute. This study looked at four glucose testing methods and the accuracy of their readings using high and low control solutions at both sea level and at depth. A one-way analysis of variance showed significant differences with all of the high and 75% of the low control solutions when comparing sea level readings to depth readings. The significance varied between reaction rate and end point reading methods, with the reaction rate technology performing better. PMID- 1620375 TI - 1991 New York-Tidewater Chapters History of Military Medicine Essay Award recipient. A snapshot of an army nurse leader in the great war. PMID- 1620374 TI - 1991 Mary J. Nielubowicz Award recipient. The nursing diagnosis: decreased cardiac output--a clinical diagnosis validation study. PMID- 1620376 TI - Health service support in Operations Desert Shield and Desert Storm. AB - Operations Desert Shield and Desert Storm have brought into focus a number of difficulties with the medical support of U.S. Army tactical forces. These difficulties include inadequate preparation of Medical Corps officers for command, inadequate medical training of field medical unit personnel, and problems utilizing available equipment to support Operation Desert Storm tactical operations. This paper will discuss these difficulties, potential solutions for these difficulties, and some unresolved issues created by or despite these potential solutions. PMID- 1620377 TI - Development of an extracorporeal liver support system: initial results. AB - A pilot study was undertaken to determine the feasibility of extracorporeal normothermic perfusion of the porcine liver. Seven donor hepatectomies were performed in small 10 kg pigs and the livers were placed in a perfusion cassette of the author's design. Four perfusions were technical failures. Three successful perfusions had several factors in common: hepatic artery inflow roller pump, prompt "pinking up" of the perfused liver, a centrifugal vena cava outflow pump with partial diversion of the outflow into the portal vein with the remaining outflow returned to the anesthetized animal, and production of bile during the perfusion experiment. Successful perfusions lasted 50, 65, and 90 minutes. PMID- 1620378 TI - Diagnostic strategy for thalassemias and other hemoglobinopathies: a program applied to the Hellenic Army recruits. AB - A program for the detection of thalassemias and other hemoglobinopathies in high risk populations is described. This program, based on two screening tests, was applied to the Hellenic Army recruits and was found to work well. Red cell one point osmotic fragility was used for the detection of thalassemic samples and hemoglobin electrophoresis for screening of other hemoglobinopathies. Samples with decreased red cell osmotic fragility and/or abnormal electrophoretic pattern were submitted for further detailed investigation. Following this program, 64,814 recruits, representing 0.651% of the total Greek population and 9.917% of the 20 year-old Greek male population, were tested. beta-Thalassemia was found with an average incidence of 5.476% and alpha-Thalassemia with an incidence of 0.201%. Hemoglobinopathy Lepore was detected in 51 samples (0.079%) and hemoglobinopathy S in 352 samples (0.543%). PMID- 1620379 TI - Ability of the Army Circumference Method to detect changes in subcutaneous fat over a 9-week period. AB - The Army Circumference Method (ACM), used to estimate percent body fat for soldiers, has been shown to have questionable validity as applied to women. This study's primary purpose was to examine the ability of this method to detect changes in subcutaneous fat over a 9-week period with men (N = 55) and women (N = 51) enrolled in a weight management program. Changes in percent body fat, based on the ACM, were correlated with the corresponding ones from the Jackson/Pollock skinfold method. Results indicated that the male ACM (r2 = 0.548) could more satisfactorily detect changes in subcutaneous fat than the female ACM (r2 = 0.135). PMID- 1620380 TI - Fat distribution: its physiological significance, health implications, and its adaptation to exercise training. AB - Recently, fat distribution has become of clinical interest in assessing one's risk for coronary heart disease (CHD). Investigations have shown stronger relationships between abdominal, or central adiposity, and various well known risk factors for CHD, than peripheral and/or total adiposity. The simple waist-to hip ratio, shown to be a valid index of such fat distribution, should be considered for use by professionals in military medicine in assessing one's risk for relevant diseases. Consideration must also be made of the role of exercise as an intervention in improving one's fat distribution profile. PMID- 1620381 TI - Battle fatigue intervention: a vital role for nursing. AB - From both a strategic military point of view and in terms of the potential for long-term psychiatric disability, the impact of battle fatigue is extremely significant. Using the basic management principles of Brevity, Immediacy, Centrality, Expectancy, Proximity, and Simplicity, all members of the health team can provide successful intervention, returning as many as 80% of battle fatigue casualties to combat. These intervention techniques can be mastered by members of all specialties, not just mental health providers. With its health education mission, professional nursing has the distinct opportunity to take a leading role in educating, not just the medics and corpsmen who will most likely be the first to encounter battle fatigue casualties, but the line community as well. It is the line commanders who can institute preventive measures to minimize the risk of battle fatigue as well as recognize early signs and initiate intervention. This paper examines the many aspects of battle fatigue from contributing factors to management principles to prevention to assist professional nurses in understanding and carrying out their role. PMID- 1620382 TI - The cosleeping habits of military children. AB - Cosleeping is a topic frequently of concern to parents; however, little objective evidence exists to support the historical prohibition against children sleeping in the same bed with their parents. Surveys from the parents of 86 children in the clinics of pediatrics and child psychiatry were analyzed to describe patterns of cosleeping in a group of military dependents aged 2 to 13 years. Shown is a significant increase in cosleeping with father absence and that cosleeping is less frequent in the psychiatric subpopulation. PMID- 1620383 TI - Impact of dental sick call on combat effectiveness: the Dental Fitness Class 3 soldier. AB - Dental sick call can have a significant impact on combat effectiveness, a loss of up to 18,720 man days per division per year. This study identified two target populations that interceptive dental treatment could best be directed toward. They are the E-1 to E-3 pay grades and soldiers in combat arms units. This study also offers dental resources needed to treat various target populations. PMID- 1620384 TI - Predictability of the individual outcome of a physical training program of an Army Special Forces Unit. AB - In a search for parameters that could predict the chances of success in a 3-month basic training program of a Special Forces unit, 293 conscripts were studied before the start of the training period. Physical activities, smoking habits, and dietary and drinking habits were evaluated by questionnaire. Anthropometric values were noted. A blood sample was taken for determination of serum cholesterol, high-density lipoprotein (HDL)-cholesterol and gamma glutamyltranspeptidase (GGT). Physical capacity was assessed by bicycle ergometry. Sixty-five trainees were discontinued from the program for intercurrent diseases or trauma, 132 went successfully through the whole program (group S), and 96 trainees failed (group F). More candidates of group S stated that they participated in sports (p less than 0.01) and fewer smoked (p less than 0.01) than in group F. Trainees of group F had a higher consumption of spirits (p less than 0.05) than trainees of group S. There was no difference between the two groups in weight, percentage body fat, physical capacity, total serum cholesterol, and GGT values. HDL-cholesterol was higher in group S compared to group F (p less than 0.01). Stepwise discriminant analysis applied to anthropometric, biochemical, and cycloergometric data indicated HDL-cholesterol, height, resting heart rate, heart frequency at maximal exercise, and serum cholesterol as significant discriminating variables (p less than 0.001), giving only a 63% chance of correctly classifying the candidates. PMID- 1620385 TI - Effects of heat-exercise stress, NBC clothing, and pyridostigmine treatment on psychomotor and subjective measures of performance. AB - This study investigated the effects of pyridostigmine pretreatment, NBC protective gear, and heat-exercise exposure on psychomotor performance and subjective sensations in eight healthy male volunteers. Exercise in heat enhanced performance of vertical addition (+7.3%, p less than 0.001) but prolonged the reaction time (+4.4%, p less than 0.01). The effects of pyridostigmine, protective gear, and the interactions between the various stressors were not significant. Cognitive performance was not dependent on body core temperature. Multiple complaints of subjective discomfort arose from wearing the protective garment. The results suggest the existence of a significant subjective discomfort but an absence of major cognitive decrements in a multiple-stresses state of chemical warfare alertness. PMID- 1620386 TI - Attendance and referral patterns in a health promotion program for soldiers. AB - We studied referral patterns among 505 active duty Army participants in a heath promotion program at Fort Lewis, Washington. Over one-third (35.6%) were referred to health care providers for confirmation of cholesterol or blood pressure screening results. Fifty-two (10.3%) had elevated blood pressure screening measurements, of whom 30% had been previously diagnosed as hypertensive. One hundred forty-six had cholesterol levels greater than or equal to 200 mg/dl, 22.8% of whom were already aware of hypercholesterolemia. Referral for follow-up was not associated with race, sex, or rank after controlling for age. Screening resulted in a large number of referrals for previously unrecognized abnormalities. PMID- 1620387 TI - Who should command? The debate continues. PMID- 1620388 TI - Who should command? The debate continues. PMID- 1620389 TI - Who should command? The debate continues. PMID- 1620390 TI - Youth attempted suicide. PMID- 1620391 TI - A brief survey of chemical defense, crew rest, and heat stress/physical training issues related to Operation Desert Storm. AB - A brief questionnaire was administered to 148 soldiers, over two-thirds of whom were aviators, at the conclusion of Desert Storm. Questions were asked about chemical defense, work/rest schedules, an aspect of pharmacological support, and heat stress/physical training during Operations Desert Shield and Desert Storm. Follow-up face-to-face interviews also were conducted with some respondents. Some of the most noteworthy findings concerned (1) training issues and side effects related to pyridostigmine bromide, (2) problems with chemical defense clothing, (3) suggestions for improving crew rest, and (4) facts about the ways in which heat-related difficulties were minimized. PMID- 1620392 TI - A new Streptococcus group A M-29 variant isolated during a suspected common source epidemic. AB - In the summer of 1988, a large epidemic of acute pharyngitis occurred in an Israeli military base. The clinical features were those of acute pharyngitis. The epidemic curve was characteristic of a common-source outbreak, possibly food borne. Throat swabs from a sample of cases were positive for group A streptococci. Nine isolates from the epidemic were further evaluated at the local reference laboratory and serotyping showed that all were of the same strain with a distinct M protein that is a hitherto undescribed variant of M-29. We discuss the significance of unusual strains of beta-hemolytic Streptococcus appearing in food-borne outbreaks. PMID- 1620393 TI - Joint task force "forward care" multicomponent health service support for an Army Reserve separate infantry brigade (mechanized)--Part III. AB - At the conclusion of 4 years' careful study of the health services support of a separate infantry brigade (mechanized) during the unit's annual training periods, the authors report on the effectiveness of a support team consisting of Army Reserve medical elements, an Active Army field unit, and a Public Health Service Clearing/Staging unit joining forces in a field environment to provide real world medical care to the same unit in a follow-on annual training period. The emphasis of the team created was on validating the forward care concept of field medical support. The result of this effort was "state of the art" medical service to the troops in the most forward areas, and a savings of 0.66 training days per soldier out of 10 days possible field training time. The cross-training of joint elements was enhanced by providing hands-on treatment of soldiers in a tactical environment, training that cannot be adequately replaced by simulated training. PMID- 1620394 TI - The utilization of medical and nonmedical specialties in the assessment of child abuse in the military community. AB - The Family Advocacy Program is a Department of Defense-mandated program that is administered individually by the branches of the U.S. Armed Forces. Factors were sought that may influence the ultimate disposition of a suspected abuse case on a given base. Navy Child Abuse Subcommittees were exclusively chaired by pediatricians, while the Army and the Air Force used social workers and psychologists. The Army and Air Force used the same medical specialists to run the larger Family Advocacy Programs, while the Navy used non-medical active duty officers. Base authorities made the final judgment to implement a treatment plan more frequently at Navy and Army commands. The implications of overutilization of medical specialists and increased legal liability of non-medical personnel are discussed. PMID- 1620395 TI - Phases of dental fear for four treatment procedures among military personnel. AB - Dental fear is a significant problem in the delivery of dental care. This study examined the phases of dental fear in 488 military conscripts scheduled to receive four categories of dental treatment for the first time. Results showed that the level of fear increased gradually from the day before treatment and peaked while receiving it. A significant reduction occurred after completing the treatment. Among the different types of procedures, tooth extraction elicited the highest degree of fear, while having the teeth cleaned registered the lowest. Military servicemen showed a pattern of dental fear similar to those other population groups. PMID- 1620396 TI - Civil unrest and ocular trauma. AB - The incidence and causes of ocular trauma among Israeli troops serving in the West Bank and Gaza between 1987 and 1989 was investigated. Of the 985 soldiers who were reported injured, 11.3% (111) were reported to have suffered from injuries to the eye. Although most of the soldiers were supplied with some kind of protective gear, only 27% reported that they received eye protection; none used this protection at the time of injury. Fifty-seven percent of the injuries were caused by stones and 38% by flying glass; 14.6% of soldiers suffered bilateral eye injuries. Only 12.1% of those injured wore corrective lenses. Although only 5% were originally reported to have suffered moderate to severe injuries, 38% complained of residual vision impairment. Better eye protection and enforcement of orders to use such gear would reduce the number and severity of ocular injuries. PMID- 1620397 TI - A mass casualty while in garrison during Operation Desert Storm. AB - In the theater of operations, rear echelon hospitals by doctrine receive patients who have been stabilized by forward hospitals. Occasionally, mass casualties will occur in the rear area, but rarely from combat causes. This report documents a mass casualty occurring in garrison from an anti-tank weapon misfiring. All rear echelon hospitals, regardless of their mission, must be prepared for the acute care of combat mass casualties. PMID- 1620398 TI - Anatomy of a contract. AB - Medical planners are constantly searching for new initiatives to solve the health care provider shortage. One of the most widely used methods to meet this need is contracting. This article focuses on the essential steps necessary to develop a successful contract using the Direct Health Care Provider Program. It also outlines the differences between personal services and non-personal services contracts. PMID- 1620399 TI - Pharmacoepidemiology and military medical automation: opportunity for excellence. AB - Fielding of the Composite Health Care System (CHCS) brings an unparalleled opportunity for medical research. This sophisticated automated medical record system promises pharmacoepidemiologic research of a quality and quantity never before possible. Pharmacoepidemiology provides answers about the validity of beneficial and adverse drug events and aids in individualizing drug therapy. When CHCS eventually encompasses an estimated 9.1 million patients at 166 military hospitals and 588 clinics around the world, it will provide a database capable of supporting sophisticated automated research. In addition to the unprecedented size of this resource, advantages of pharmacoepidemiology performed with the CHCS database include integration of inpatient and outpatient care records, the completeness of prescription and medical records, and the wide socioeconomic spectrum covered in a defined population. Limitations and potential biases of such a database include separate drug formularies at each medical treatment facility, only limited information about nonprescription drug use and single-dose drug orders in clinics, and the mobility of military service members and their families. Pharmacoepidemiology is a tool that will benefit individual members of the military family, as well as advancing the sciences of pharmacy and medicine. Using the CHCS database for this form of research is in the best tradition of military medical research. PMID- 1620400 TI - Reaction of Army families with grade school children to the Active Duty Dependents Dental Insurance Plan. AB - In March-May 1988, we collected data on enrollment of 1,445 Army families with grade school children in the Active Duty Dependents Dental Insurance Plan at two Army posts. We also surveyed their reactions to the plan. Results show that, although nearly two-thirds of families are enrolled in the plan, most consider the plan a loss of benefits and coverage inadequate. Queues and limited services at military clinics are primary reasons for joining; poor coverage of the dental insurance plan is the main reason for not. A majority of families are willing to pay more for expanded coverage. PMID- 1620401 TI - Peer review: determining what's best for patients by professional self assessment. AB - Many influences outside of physician control have begun to undermine traditional physician autonomy. Studies of physician practices reveal differences not based on patient case mix alone, but on variations in decisions and lack of intra physician accountability. Failure of physicians to be accountable to each other is related to inadequate due process understanding, fear of legal recriminations from peers, and a traditional long-standing history of individuality and accountability. The malpractice crisis and the advent of a National Practitioner Data Bank of physicians whose privileges or licenses have been modified serves as an impetus to rebuild accountability into a new emphasis on peer review based on optimum patient-focused outcome. To get physician buy-in, a five-step process is described which is separate from professional review of privileges and is seen as collegial, educational, and patient focused. PMID- 1620402 TI - The National Practitioner Data Bank: an introduction. AB - The National Practitioner Data Bank, mandated by law, has created a great deal of anxiety in the medical community. The author describes the origin, development, and operation of the bank. Army implementation procedures emphasize safeguards for practitioners and are also felt to be fully consistent with patient protection. Potential problems and areas for further research are described. Linking practitioner entry to standard of care or setting a dollar cut-off for entries are two possible solutions. PMID- 1620403 TI - The Klippel-Feil syndrome: implications for Naval service. AB - The Klippel-Feil anomaly is usually discovered by serendipity on cervical spine X rays. Although it may encompass many vertebrae, the typical case is an isolated fusion of two vertebrae. Nearly 1% of the general population has this anomaly and its incidence in the Navy is likely similar. Increased susceptibility to spinal cord injury has been reported in individuals with the Klippel-Feil syndrome. Unusual stress on the head and neck inherent to various aspects of naval service place such persons at risk for debilitating or fatal injury. An algorithm for evaluating suspected Klippel-Feil syndrome is provided. PMID- 1620404 TI - Graphite tattoo: report of a case and differential diagnosis. AB - A case report underlining the necessity of the biopsy procedure for a pigmented lesion of unknown origin. A female patient was referred for evaluation of a pigmented lesion on the facial keratinized gingiva coronal to the free gingival margin above tooth No. 7. An excisional biopsy revealed a graphite tattoo. A discussion and differential diagnosis of pigmented lesions follows. PMID- 1620405 TI - Displaced stress fracture of the femoral shaft: a report of three cases. AB - Three cases of displaced stress fracture of the femoral shaft are reported. All patients were young conscripts. Before displacement, the patients had suffered from knee and distal femoral pains for 2-6 weeks. All fractures were located at the border of the middle and distal third of the femoral shaft and had a short oblique form. Plating was performed in two and intramedullary nailing in one case. A fast bony union into a good position was achieved in all cases. Scintigraphy is indicated for an early diagnosis, which enables conservative treatment and prevention of the fracture displacement. PMID- 1620406 TI - One medical center's journey into continuous quality improvement. PMID- 1620407 TI - [Catheterization of the pulmonary artery in 1,207 patients]. AB - The pulmonary artery catheterization has been reviewed in 1207 patients submitted to cardiovascular surgery. The feasibility of the technique in skilled hands has been outlined and a routine and prophylactic use of pulmonary artery monitoring as a safe way to manage critically ill patients has been advocated. PMID- 1620408 TI - [Anesthesiology problems in the surgery of cervico-mediastinal goiter. Our clinical experience]. AB - The Authors, after explaining the difficulties that an anaesthetist finds in cervical-mediastinum goitre surgery, report their own experience. Even if limited, it shows the full validity of a methodology of using a very efficacious drug for good cardiovascular stability. Moreover, we must take into account the constant attention the anaesthetist must pay in some essential moments of general anaesthesia such as intubation, patient position and monitoring. PMID- 1620409 TI - [Tetanus disease. Experience with 2 intensive treatments during 13 years]. AB - The Authors present a retrospective analysis of 58 cases of tetanus hospitalized in two ICU in 13 years of activity. The mortality reported (39.7%) is comparable to other Authors or statistical analysis but it is better if correlated to patient age. Patients of the highest classes (III and IV classes of Edmonson e Flowers) had the highest mortality but no significant variation was seen between patients of the III and IV class. The most frequent cause of death has been cardiac arrhythmia. Cardiac arrhythmias happened in most cases in the first 15 days of hospitalization. 37.9% of patients developed pneumonia: prolonged hospitalization (more than 15 days) and high classes of the disease have been the most important risk factors for Hospital-acquired pneumonia in tetanic patients. PMID- 1620410 TI - [Propofol, fentanyl, nitrous oxide: useful and current combination?]. AB - The introduction of use of propofol in the anesthetists' pharmacopoeia has reinvigorated the research for a totally intravenous anaesthesia, for which the Authors propose a diagram. However, in experience related to the supplementary use of N2O, in virtue of its analgesic power, demonstrates yet another utility, permitting an easier anesthetical administration with minor consumption of intravenous drugs. PMID- 1620411 TI - [Propofol in gynecologic ambulatory minor surgery]. AB - We have reported the results of 700 general anesthesia induced and maintained by Propofol in women who have undergone IVG operation. The anesthesia-method used has guaranteed an adequate level of anesthesia with the characteristics of a quick induction, non significant variations of the cardiovascular parameters, a quick recovery of consciousness, low incidence of side effects, the abolition of the azote-peroxide and the halogen-anesthetics, a quick discharge of the patients. PMID- 1620412 TI - [Sedation with continuously infused propofol in caudal block for elective pediatric surgery]. AB - Twenty-nine patients aged between 2 months and 6 years, undergoing general surgery under regional analgesia (caudal block) combined with continuous infusion of propofol (3 mg/kg/h), were studied. During anesthesia the heart rate, the arterial pressure, the SaO2 and respiratory rate were recorded; the electrocardiogram was continuously displayed and all side-effects occurring during maintenance and recovery from anesthesia were noted. Satisfactory sedation without significant respiratory and cardiovascular depression and a rapid recovery, was observed. In conclusion, we feel that the use of combined caudal block and continuous infusion of propofol for paediatric surgery is rational. PMID- 1620413 TI - [Loco-regional analgesia with continuous peridural technique in labor. Evaluation of 4 years of experience]. AB - The Authors report on the results of their experience using local-regional analgesia performed with the continuous peridural technique over four years of activity with 503 pregnant women. Protocols used over the years called for morphine-fentanyl association, but bupivacaine 0.25% plus fentanyl and bupivacaine 0.125% plus fentanyl mixtures were then employed. In order to evaluate the efficiency of this procedure, the following data were recorded for each patient undergoing the analgesia: duration of labor prior to the effect of the analgesia; time to reach complete dilatation from a 3 cm dilatation; the length of time of the expulsive phase; manifestation of side effects and complications; vacuum utilization. Furthermore, Apgar scores were taken for all newborn babies at 1st and 5th minutes. The data were then compared with those recorded for a group of women with the same obstetrical characteristics who were not treated with analgesia. The comparison showed that the length of time of the dilatation phase (from 3 to 10 cms) was significantly less in the group of treated patients, while the expulsive phase was basically similar in both groups, thus showing that labor mean time had significantly decreased in the group of patients treated with analgesia. The number of vacuum births was basically the same in both groups and comparable to the data available in the literature. These were practically no side effects or complications. In conclusion, our experience confirms the fact that this method is the most reliable in terms of safety, effectiveness and acceptability on the part of women compared to any other analgesic treatment employed during labor. PMID- 1620414 TI - [Oxycodone versus paracetamol in oral premedication in cholecystectomy]. AB - This double-blind study was carried out at random on 2 groups of 10 women, comparable by age and weight, all having to undergo a cholecystectomy as a result of gall-bladder stones. Group A received 10 mg os of oxycodone, while group B received 1000 mg os of paracetamol. The level of sedation before the operation, post-operative pain, canalization and the side effect were recorded. The results showed that the group treated with oxycodone presented a greater degree of pre operative sedation. As far as the post-operative pain is concerned, no significant differences were seen between the two groups based on both what was expressed by the patients and what was reported by a visual analog. Furthermore, no significant differences were noted as far as the side effects and canalization are concerned. PMID- 1620415 TI - [Benzodiazepine and flumazenil in elective electric cardioversion]. AB - The Authors report on the use of Flumazenil (Antagonist of the benzodiazepines in the CNS) in patients awakening from benzodiazepine induced necrosis for defibrillation. When used in these circumstances, the normal side effects of the narcosis (arrhythmia, rebound hypertensive convulsions, states of paradoxical anxiety) were almost completely absent. Furthermore, given the optimal quality of the rapid awakening, in about 5 minutes, the antagonistic qualities of the drug were confirmed making further development of the therapeutic uses of the benzodiazepines possible. PMID- 1620416 TI - [The use of systemic phosphocreatine in heart surgery]. AB - Phosphocreatine (PC) has been widely used in cardiac surgery as a component of cardioplegic solutions because of its positive effects in preventing ischemic heart damage; we have researched the efficacy of PC in cardiac surgery when infused through the intravenous route before and after cardiac arrest. Two groups of patients who had undergone aortocoronary by-pass grafts were matched: group A (20 patients) did not receive any particular treatment; PC was administered intravenously to patients in group B after the induction of anaesthesia, immediately prior to cardiac arrest and after the release of aortic cross-clamp. To test the efficacy of the drug, the following parameters were evaluated: the recovery as the incidence of low cardiac output and/or need of inotropic drugs; dysrhythmias; electrocardiographic signs of myocardial ischemia or infarction; release of cardiac necrosis enzymes. Treated patients were found to have a better recovery, a lower incidence of dysrhythmias, an easier resumption of normal sinus rhythm with a lower number of electric defibrillations and a significantly lower release of cardiac enzymes. It can be therefore said that PC has a marked protective effect on myocardial anoxia in cardiac surgery, even when administered intravenously. PMID- 1620417 TI - [Comparative study of the effects of famotidine and omeprazole in the prevention of the aspiration of gastric contents syndrome in elective surgery]. AB - This study compares the efficacy of omeprazole and famotidine in reducing gastric volume and activity. Sixty patients scheduled to undergo elective orthopaedic surgery were randomly allocated to receive famotidine 40 mg or omeprazole 40 mg at 22 hours, the night before surgery, or omeprazole at 22 hours the night before and 20 mg at 6 hours on the morning of surgery, 20 patients served as control and received no drugs. Intragastric volume and pH were measured immediately after induction anaesthesia and after surgery. Either drug reduces gastric volume. Famotidine reduces at maximum volume. Omeprazole reduces at maximum pH. Omeprazole 40 mg in some cases doesn't sufficiently reduced pH, because the interval from drug administration to induction of anaesthesia is too long. The comparably high volume of gastric content after omeprazole in single or double dose doesn't represent a risk. PMID- 1620418 TI - [Diagnostic usefulness of BAEPs. A clinical case]. AB - We report the clinical case of a patient operated for a right extracerebral haematoma. In the immediate post-operative period, although no clinical signs were present, a BAEP examination (showing the lack of the V) warned of a pathological condition which was ascertained by CT. A second haematoma was observed, contralateral to the first, and immediately removed. In this case, therapy was based on the neuroelectrophysiological findings. PMID- 1620419 TI - [Isolated postoperative myoglobinuria as the only sign of malignant hyperthermia. Value of spinal anesthesia with bupivacaine in a posterior surgical intervention]. AB - The Authors report a case of biopsy-proven malignant hyperthermia in a pediatric patient who underwent general anesthesia with halothane and succinylcholine for foot surgery, in whom the presenting symptom was isolated postoperative myoglobinuria. The above syndrome, in the absence of a positive family history, may present itself with a set of minor and atypical symptoms, thus being often underestimate. The need for further investigating all the cases of postoperative myoglobinuria is stressed by the Authors, which also consider muscular biopsy for inclusion among routine investigations. In the case reported here, six months later, a new surgical operation was done safely with spinal anesthesia using hyperbaric bupivacaine. PMID- 1620420 TI - [The use of propofol in a female patient predisposed to malignant hyperthermia (central core disease)]. AB - In this paper the Authors describe the anesthetic techniques used for abdominal surgery in a 19 year-old woman with "central-core disease". This uncommon congenital neuromuscular disorder is frequently related to malignant hyperthermia syndrome. Total intravenous anesthesia with the association propofol-fentanyl was well tolerated by the patient. There was no evidence of malignant hyperthermia during the procedure and cardiovascular stability was excellent. PMID- 1620421 TI - [The use of intravenous nifedipine for the treatment of severe hypertensive crisis. A clinical case]. AB - Nifedipine is a calcium channel antagonist. Hypertensive crisis during anaesthesia may be elicited during the induction period or by the surgical manipulating of intrapelvic viscera. We report a case in which nifedipine given intravenously (currently an investigational dosage form) was effective in controlling a severe hypertensive crisis at dose averaging 3.4 mcg/kg/min initially and half as much for maintenance. Arterial pressure was controlled as quickly as with nitroprusside, but with no change in heart rate or cardiac output and without other untoward effects during anaesthesia. PMID- 1620423 TI - [7th Italian-French Meeting of Neuroanesthesia and Resuscitation. Positano, May 18-20, 1992]. PMID- 1620422 TI - [Acute pulmonary edema after intravenous naloxone]. AB - We present one case of pulmonary edema following intravenous naloxone administration for antagonism of residual narcotic drugs. The patient was a young man without cardiopulmonary or neurologic disease. Pathogenesis results from a massive sympathetic discharge which leads to neurogenic pulmonary edema. PMID- 1620424 TI - [Peri-operative complications of intravascular treatment of cerebral aneurysms and extra- and intracranial vascular malformations]. PMID- 1620425 TI - [Intra- and postoperative anesthesiologic management in cerebral arteriovenous malformations]. AB - The authors analyze the anesthetic management of 59 cases of "large" arteriovenous malformation (more than 20 cm3), all completely removed by microsurgical technique. The discussion is focused on immediate pre-operative, intra-operative and post-operative pharmacological treatments in order to reduce the hemodynamic effects in the surrounding brain after excision of angiomas. PMID- 1620426 TI - [Risk of postoperative epilepsy in acute surgery of cerebral aneurysms]. AB - Forty-nine patients operated during an early clipping phase of cerebral aneurysm were reviewed; none had an associated ventricular flooding and/or intraparenchymal hematoma. Starting from the day of operation 37 patients were treated with anticonvulsant drugs using methods and dosages where were unlikely to guarantee efficacious cover. Forty-two patients made a satisfactory recovery, 5 patients died and 2 had severe neurological sequelae; 2 patients (4.4%) had early seizures during the first week after operation. In view of the inadequate cover of the anticonvulsant drugs and the homogeneous clinical characteristics of patients included in the study, the low number of attacks suggests an overall re evaluation of anticonvulsant treatment and the need to select patients with a higher risk of an epileptic attack. PMID- 1620428 TI - [Intracranial meningioma in patients over 65 years old. Risk factors and complications in a consecutive series of 124 cases]. PMID- 1620427 TI - [Complications during preoperative embolization in intracranial meningioma]. AB - We report a rare case of meningioma of the parieto-occipital convexity accompanied by hemorrhage in the tumor and in the subdural space that occurred while pre-operative embolization was being applied. The patient, a 48 year old woman, presented sudden headache and, in a few minutes, comatose status and decerebrate rigidity. A quick diagnosis with CT-scan of acute intratumoral and subdural hemorrhage and a rapid intervention on the patient led to complete recovery. The possible reason for the hemorrhage is the sudden change in blood pressure of pathologic small vessels triggered by embolization. PMID- 1620429 TI - [Total intravenous anesthesia in neurosurgical patients]. AB - The authors present an anesthesiologic technique, consisting of the use of propofol + fentanyl + O2. The main advantages, described in 82 neurosurgically treated patients, are the following: moderate decrease both of ICP and MAP, absence of frequency, modifications rapid recovery both of consciousness and of motility, which allows a preliminary valuation of neurological status. PMID- 1620430 TI - [Randomized study on the use of propofol for anesthesia in intracranial tumors. Comparison with balanced anesthesia]. AB - There is currently no anesthesiological technique which enables volume, cerebral blood flow and spinal fluid pressure to be kept constant. The aim of the present study was to compare two techniques of anesthesia in patients with cerebral tumours: one of a balanced type (AB) and the other of a continuous ev type (AEC) using propofol in order to assess which guaranteed the greatest cerebral protection. The results of the study have shown that the use of propofol may represent a useful alternative in intracranial tumour surgery since changes in systolic pressure and heart rate observed during AEC anesthesia were statistically lower in comparison to AB anesthesia. No statistically significant differences were observed in relation to changes in diastolic pressure, PVC, ApCO2 and the incidence of bleeding or cerebral edema. The quality of awakening was better in patients in the AEC group in terms of renewed breathing and spontaneous motility, verbal response and space-time orientation. PMID- 1620431 TI - [Anesthesia for thermocoagulation of the trigeminal nerve. Use of propofol]. AB - Propofol has been used in anesthesia for trigeminal nerve thermocoagulation. 9 patients were studied. This anesthetic agent allows speedy arousal of good enough quality for patient questioning. No cardiovascular or respiratory complications were noted. PMID- 1620433 TI - [Trans-sphenoid surgery of hypophyseal adenoma. Postoperative water-electrolyte complications]. PMID- 1620432 TI - [Tracheal intubation: increase of arterial pressure and cerebral blood flow velocity. Effect of thiopentone and propofol]. AB - Induction of anaesthesia in intracranial surgery, especially for vascular diseases, must minimize haemodynamic changes: blood pressure and cerebral blood flow must not be increased to a high degree. Our work compares increases in blood pressure and in the speed of cerebral blood flow during endotracheal intubation in two groups of patients, who received propofol or thiopentone for the induction of anaesthesia. We studied 30 patients, without intracranial diseases, who underwent lumbar slipped disk surgery. Half of the patients received thiopentone and curare before intubation and the other half propofol and curare. Increase in blood pressure after intubation was lower with propofol than with thiopentone in a statistically significant way. Also the increase in the speed of cerebral blood flow, measured with doppler technique, was lower when induction with propofol was used, though not statistically relevant. PMID- 1620434 TI - [Pansinusitis of the face caused by Streptococcus milleri with cerebral thrombophlebitis after naso-sphenoid surgery of the pituitary gland]. AB - The authors report a patient operated on trans-nasosphenoidally for a pituitary adenoma (Cushing's disease) in whom a severe infection occurred with cavernous thrombophlebitis responsible for neurological complications. PMID- 1620435 TI - [Postoperative complications of transcranial surgery for hypophyseal adenomas]. PMID- 1620436 TI - [Urapidil: hypotension induced in neuroanesthesia]. AB - The authors report their experience on the use of urapidil in 31 patients, submitted to neurosurgical procedures. Urapidil, administered both in the inductive (0.7-1 mg/kg) and in preoperative phases (0.6-0.8 mg/kg/h), produced a MAP decrease of about 25% without significant variations in cardiac frequency or of other monitored parameters. PMID- 1620437 TI - [Labetalol in the prophylaxis of postoperative arterial hypertension in surgery of the posterior cranial fossa]. AB - Increased catecholamines are one of the factors responsible for post-operative arterial hypertension. In order to prevent this severe complication labetalol, an alpha and beta blocking drug, was infused following the closure of the dura mater in half of the patients studied. For two hours after surgery blood pressure values in treated patients were constantly lower than those recorded in the control group, thus confirming the efficacy of this drug in preventing the cardiocirculatory effects of increased adrenalin and noradrenalin. PMID- 1620438 TI - [Early epilepsy in surgery of extra-axial supratentorial neoplasms]. AB - A retrospective study was performed to evaluate the incidence of seizure and anticonvulsant prophylaxis in 138 patients operated from september 1987 to august 1989 for extra-axial supratentorial tumors. 15 patients (10.9%) developed seizures in the early post-operative period. We have considered the importance of histological type and side of lesions, a previous history of epilepsy and the pre and intraoperative prophylaxis. We can say that there is a statistical significance between sellar and middle cranial fossa tumors and the frequency of post-operative epilepsy and that anticonvulsant prophylaxis can reduce post operative seizure. There is no statistical significance between the previous history of epilepsy the type of anesthesia and post-operative seizure. PMID- 1620439 TI - [Postoperative complications in neurosurgery]. AB - Hemorrhage, ischemia and ischemic edema are among the complications which may occur following neurosurgery and they represent the most frequent cause of neurological deterioration. The mechanisms predisposing vascular complications (hemorrhage, ischemia) are described and discussed in relation to systemic alterations associated with surgery and anesthesia. In addition, the physiopathology of these complications is discussed in the various pathologies: cancer, vascular malformations, trauma and the intra-operative diagnostic possibilities which prevent their onset. PMID- 1620440 TI - [Postoperative epilepsy. Experience with 300 cases of cerebral neoplasms]. PMID- 1620441 TI - [Postoperative epilepsy]. PMID- 1620442 TI - [Psychic disorders. An unknown complication of surgery of the posterior cranial fossa]. AB - Psychic trouble is not generally recognised as a possible complication of posterior fossa surgery. Reviewing a series of 63 pediatric patients operated on for posterior fossa intraxial tumors, the Authors found 21 cases of psychic troubles in the post-operative period. The incidence was higher in: a) medulloblastoma; b) rostral vermis location; c) supracerebellar infratentorial and transvermian approach. The neuropathophysiological basis of the phenomenon is discussed. PMID- 1620443 TI - [Increasing the pressure of cerebral perfusion to control intracranial pressure]. AB - ICP control can be achieved removing the surgical masses and manipulating the intracranial compartments; in the intensive care setting that can be attempted using CSF withdrawal or changing the cerebrovascular resistances, the intracranial blood content and the cerebral water content. The reduction of the ICP and the maintenance of a good cerebral perfusion pressure are the main aims of the therapy; when any standard treatment fails to control ICP a further attempt to preserve cerebral perfusion should be done by increasing the mean arterial pressure. In 10 patients with severe brain damage (GCS on admission ranging from 3 to 7, mean 5) from subarachnoid hemorrhage (3 cases) or trauma an infusion of dopamine (25-150 mg/h) and noradrenaline (0.4-2.4 mg/h) was started in case of intractable ICP. The ICP was defined intractable when the pressure was more than 40 mmHg for more than 5 m' after maximum therapy, as evaluated using the Therapy Intensity Level score. The infusion obtained a raise of the MAP of approximately 25% and a variable response on ICP. In 9 cases ICP dropped, in one case, instead, the ICP increased together with the arterial pressure. The reduction of ICP was 20-30%, with a good improvement of the CPP. The patients with a good response survived, the only patient without control of the ICP died. The physiopathologic mechanisms of this treatment are discussed; the most suitable explanation is indicated in an autoregulatory process. The infusion of cathecolamines can be harmful, and the patients eligible for this treatment must be carefully chosen. Notwithstanding this approach deserves further studies for the cases of intractable ICP. PMID- 1620444 TI - [The risk of pulmonary embolism in neurosurgery]. AB - Pulmonary embolism (PE) is a frequent necroscopic finding in neurosurgical patients and this contrasts with the difficult diagnosis of it when the patient is still alive. Such a lack of diagnosis has promoted numerous studies into deep vein thrombosis (DVT) which is, in most cases, the cause of pulmonary embolism. However, a prophylaxis of DVT cannot be indiscriminately carried out in neurosurgical patients because it is not without potential risks. For this reason we considered it useful to investigate whether among the risk factors for DVT there were any particularly responsible for the development of PE in neurosurgical patients. Our case study was carried out retrospectively on 144 patients hospitalised in the Neurosurgical Institute of Pisa University suspected of PE. In 88 of the cases the suspicion had been confirmed by perfusion lung scanning; in 56, on the other hand, it had been excluded. These two groups of patients resulted homogeneous for sex, age, blood group, and for the presence of any risk factors of cardiovascular diseases. An important difference between the two groups was the pathology which had motivated their hospitalisation; in fact, 50% of the patients with PE were affected by neoplastic pathologies of the CNS, against 28% of the others. The anamenestic evidence of previous neoplastic pathology in different sites of the CNS was much more frequent in patients who had developed PE. As far as the other risk factors we examined are concerned, it resulted that only 12.5% of the patients with PE had presented clinical signs or symptoms of phlebitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620445 TI - [Hypertensive pneumocephalus, postoperative complication of chronic subdural hematomas]. AB - The authors report 3 cases of subdural tension pneumocephalus developed after surgery for subdural chronic hematomas. The mechanisms involved in the pathogenesis of this complication are discussed; the importance of the computed tomography in the assessment of the subdural tension pneumocephalus is stressed. Surgery is always indicated in cases of increased tension of the air collection and generally resolves the neurological deficits. PMID- 1620446 TI - [Neuroanesthesia during carotid thromboendarterectomy interventions]. AB - The paper describes two techniques of anesthesia used during carotid thromboendarteriectomy surgery. The first technique utilises a mixture of O2-N2O, isofluorane and fentanyl as analgesic; the halogenate compound is not administered during carotis clamping and fentanyl is used for maintenance. The second technique is predominantly intravenous and utilises differing doses of propofol during the entire operation with fentanyl as an analgesic. The two techniques are comparable in terms of management and efficacy; the use of ECG monitoring is vital to identify possible intraoperative cerebral ischemic phenomena. PMID- 1620447 TI - [Operative posture in pediatric neurosurgery]. AB - Proper placement of the pediatric neurosurgical patient is strictly correlated to age (newborn, toddler, infant, juvenile). Each age group is reviewed on the basis of different morphological and pathophysiological aspects of typical neurosurgical positions (prone, supine, sitting, lateral). PMID- 1620448 TI - [Complications of the surgical treatment of traumatic lesions of the cervical spine]. PMID- 1620449 TI - [Prevention of postoperative complications in vertebro-spinal cord pathology]. AB - In 352 patients, affected by vertebral-medullary pathology, we evaluated the role played by the prevention or by the treatment of postoperative complications. We also evaluated their influence on the clinical outcome and neurological recovery. In every case we recorded a scrupulous post-operative neurological monitoring of the eventual complications, on the basis of the type, gravity and duration. From our results it appears that the complications, mostly secondary to infectious diseases, have an influence on the clinical and neurological recovery. We highlight the importance of an adequate nutritive management to prevent the complications, specifically those secondary to infectious diseases and cutaneous lesions. PMID- 1620450 TI - [Postoperative lumbar discitis]. AB - The authors report our experience on 19 cases of discitis developed after operations for herniated lumbar disc. Because of the negativity of the neuroradiological studies in the acute stage, the recognition of the typical syndrome (severe back pain, spasm of the paravertebral lumbar muscles, limited spinal motility, fever) beginning 3-30 days post-operatively and the study of some laboratory tests (elevated Erythrocyte sedimentation rate (ESR) and midly to moderately elevated white blood cells (WBC) are very important for diagnosis. The first radiographic findings (disc space narrowing, ecc.) are detectable only 4 to 6 weeks after the first symptoms; other X-ray findings are not seen post operatively before 6 months-2 years. The CT-scan is diagnostic of discitis only when the following three specific signs are present: a) anterior paravertebral soft tissue swelling with obliteration of paravertebral fat planes; b) fragmentation or erosion of vertebral end plates; c) paravertebral fluid collection (abscess). In our experience a period of immobilization of the spine with a plaster body jackets and the use of adequate antibiotic therapy are the more effective treatment. Undoubtedly the discits are the results of an infection that must be prevented adhering to the aseptic principles not only during surgery but also during the procedures performed in the radiology suite. PMID- 1620451 TI - [Cranial trauma and prehospital care. Evaluation of the effectiveness of early treatment]. AB - The role of pre-hospital care is still to be stressed especially in case of head injuries. We compared two groups of head injuries (total 50 patients, 38 politrauma) transported by traditional ambulance (28 patients) or by EMS helicopter (22). The two populations had similar values of the considered indices (TS, ISS, GCS, TRISS). They significantly were different only for the "free therapy time". Patients transported by ambulance showed an higher incidence (p less than 0.01) of acute complications (like hemorrhage and hypovolemic shock) despite the same gravity score indices. The index applied for the follow-up valuation, does not show any difference in the two groups. This may be due to the unreliability of the used scores if they are applied without any correlation with the quality of care during the transport. PMID- 1620452 TI - [Severe head trauma in the pediatric patient. Our experience]. AB - A retrospective study in a pediatric population of 324 severe head trauma patients hospitalized at Santobone Children's Hospital has been carried out; diagnostic investigations and therapeutic aspects are stressed on the baw of pathophysiological features of such patients. PMID- 1620453 TI - [Continuous monitoring of O2 saturation in cerebral blood. A guide for the nursing of brain trauma patients in coma]. AB - Manual ventilation is frequently performed by nurses to control increases in intracranial pressure (ICP) or during physiotherapy in head injured comatose patients. The effects of manual ventilation (n = 251) on ICP, cerebral perfusion pressure (CPP) and EEG have been studied in 18 mechanically ventilated patients. A fall in ICP was easily obtained but a fall in arterial blood pressure was often present at the same time. Thus a reduction in CPP resulted in 36% of occasions. Prophylactic boluses of thiopental (n = 67) before noxious stimuli obtained a fall in ICP in 99% of occasions but resulted in a decrease in CPP in 46%. The fall in ICP, due to the decrease in cerebral blood flow (CBF) by hypocapnia or metabolic depression and/or arterial hypotension, may be beneficial in hyperaemic brains but may precipitate cerebral hypoxia in ischaemic lesions. Relevant information about cortical metabolism (CMR) may be obtained from EEG monitoring by Cerebral Function Monitor but, unfortunately, no data about CBF are clinically available. The Authors suggest that the continuous monitoring of jugular bulb oxygen saturation (SjO2) may offer a clinically useful index of CBF adequacy to CMR. Findings from a preliminary study in 5 patients demonstrate that a severe decrease in SjO2 has been frequently caused by manual ventilation, hypothetically related to severe cerebral ischemia. High levels of SjO2 have been induced by endotracheal suction and physiotherapy, probably related to severe hyperemia. As prevention of ischaemic and hyperaemic insults is a major goal of treatment, the A. suggest that these undesirable effects of nursing might be avoided if nurses could take advantage of continuous monitoring of SjO2. PMID- 1620454 TI - [Complications of trans-sphenoidal surgery of the sellar lesions]. AB - Trans-sphenoidal surgery has a very low rate of complications despite a series of apparently negative anatomo-topographical factors. Complications may be either mechanical or functional, transitory or permanent. The most important complications are: hematoma of the focus, sub-arachnoid hemorrhage, empty sella, liquoral fistula, opto-chiasmatic lesions, arterial lesions, lesions of the cavernous sinus, parenchymal damage, nasal and paranasal mechanical lesions, insipid diabetes, hypopituitarism. The overall mortality rate is 0.4-1% and is always associated with predisposing factors, such as previous treatment, voluminous extrasellar growth, concomitant causes of disease; the most frequent causes of death are: hemorrhagic phenomena in the extrasellar portion of large size adenomas; vascular lesions involving the intracavernous carotid artery; and hypothalamic lesions. The frequency of major complications is in the region of 2.3%. Predisposing factors are: volume, consistency, invasiveness, previous treatment, intratumoral necrotic-hemorrhagic phenomena, age. Surgery is only indicated for some of the above complications, including hematoma of the focus, acute postoperative empty sella, rhinoliquorrhea resistent to conservative treatment, excessive filling of the sellar cavity. All the other possible complications are results or functional alterations which must be treated medically, even if a specific therapy only exists for some (such as early hypotonic polyuria). The series of patients reported here refers to the period 1978-1989 and accounts for a total of 259 trans-sphenoidal operations performed in 245 patients. Of the secondary operations, 6 were due to postoperative complications (hematoma of the focus in 2 cases, rhinoliquorrhea in 2 cases; empty sella and hemorrhagic infarction of a large suprasellar site in the 2 remaining cases). There were 2 deaths related to direct mechanical complications (both caused by hemorrhagic infarction of large tumoural residues and the surrounding cerebral parenchyma). Complications which did not require re operating were observed in 11 further cases: 6 cases of persistent rhinoliquorrhea which required protracted spinal drainage; 2 cases of deterioration of previous visual deficits unrelated to either hematoma of the focus or empty sella but caused by trauma to optic structures, either directly or on a vascular basis; 3 cases of dyplopia due to oculomotory deficiency. In terms of hypophyseal function, the ex-novo onset of postoperative pan-hypopituitarism and insipid diabetes was only observed in one case.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1620455 TI - [Infective complications of external ventricular shunts]. AB - Since the sixties at our Department of Neurosurgery, we use an original method for external ventricular shunts. To verify the effectiveness for reduction of infections risks the Authors have retrospectively analyzed 95 patients: only 4 cases of meningitis have been observed. The Authors consider the utility of the proper method and the importance of the duration of ventriculostomy placement. PMID- 1620456 TI - [Intravenous immunoglobulin in the prevention of infections in high-risk pediatric neurosurgery]. AB - Sixty-four children undergoing "high risk" neurosurgery, were submitted in a comparative study performed to investigate the prophilactic effect of IgIv in reducing the risk of postoperative sepsis. Patients were divided in two groups that weren't different as to underlying disease, age and sex. 32 patients received IgIv 0.2 g/kg on day 0, day 2, day 5, day 12 and 32 placebo. IgIv reduced the number of postoperative respiratory and urinary infective events, thus resulting in a marked reduction of the therapeutic use of antibiotics. No side effects of administration of IgIv were observed. PMID- 1620458 TI - Malignant hyperthermia. PMID- 1620457 TI - [Cerebral edema: osmotic therapy in clinical practice]. AB - Having described the therapeutic protocol to be followed in cases of cerebral edema, starting with aspecific measures (hyperventilation in a position of 30 degrees, etc.) for slight cases and progressing to specific therapy (osmotherapy, barbiturates) for more severe cases, the paper focuses on osmotherapy and illustrates the theoretical principles on which it is based and its use in clinical practice. PMID- 1620459 TI - [Complications of intracranial neoplastic pathology]. AB - Post-surgical complications in the treatment of intracranial tumors, independently of their location, are summarized in 5 essential points: a) edema; b) hemorrhages; c) ischemias; d) infections; e) alterations of the liquoral dynamics. According to our experience, it is possible to minimize these complications by using convenient intraoperative surgical procedures. On this subject, in addition to the traditional microsurgical techniques, the use of the high technologies (Cusa, laser) is very advantageous. In conclusion the important role of neuroanaesthesia and of the post-operative intensive care is underlined. PMID- 1620460 TI - [Postoperative cerebral edema. Physiopathology of the edema and medical therapy]. AB - Cerebral edema complicates many neurosurgical conditions, such as head injuries, neoplasms and infections, and is the direct result of operative trauma. The recognition and the treatment of brain edema are of great practical importance, particularly in those conditions leading to brain herniations and/or intracranial hypertension. Brain edema can be distinguished into two major categories, based on the integrity of the blood brain-barrier (BBB). With intact BBB edema, the crucial pathogenic event is related to disturbances of cellular metabolism and ionic transport. All the cellular elements of brain may undergo swelling, with a concomitant reduction of the extracellular-fluid space of the brain. Open BBB edema, the most common form of brain edema, is characterized by increased permeability of the brain endothelial cells. Brain edema results from the oncotic forces generated from a serum protein influx into the nervous tissue, and edema fluid accumulates primarily in the extracellular space. The non-operative management of brain edema requires attention to the causes that have induced brain edema. Specific pharmacologic therapy with corticosteroids, hyperosmolar agents and furosemide or acetazolamide depend upon accurate assessment of BBB integrity. PMID- 1620461 TI - [Water-electrolyte imbalance following neurosurgery]. PMID- 1620462 TI - [The physiopathology of oxygen venous saturation]. AB - The paper underlines the importance of continuous SvO2 monitoring by means of the insertion of a modified Swan-Ganz optic fibre catheter into the pulmonary artery. Following an analysis of the factors which regulate O2 transport and ATP formation, together with metabolism self-regulating mechanisms which intervene in periods of stress to guarantee cellular metabolic activity, the Authors underline the importance of SvO2 as an indicator of the balance between O2 demand and supply. Real-time SvO2 monitoring is therefore considered a valuable and early marker of rapidly degenerating biological processes in critical patients. PMID- 1620463 TI - [Postoperative infective complications in neurosurgery]. PMID- 1620464 TI - [Epileptogenic complications of neurosurgical interventions]. AB - Epileptogenic complications after supratentorial intracranial surgery are, strictly defined, the events which promote a further complication, i.e. seizures in any form, partial, simple or complex, or generalized. The most common epileptogenic complications are, therefore, electrolyte imbalance, hypoxia, hypoglycemia, hypocapnia, and intracerebral or extradural hematoma. However, also inadequate anticonvulsant prophylaxis and use of convulsant drugs can yield to the onset of post-operative seizures. Anesthetic drugs have been each time defined pro or anti-convulsant: however, data from the literature show that it is not possible to certainly define the role of general anesthetics in the genesis of post-operative seizures. PMID- 1620465 TI - [Metabolic and water-electrolyte changes as postoperative complications in aneurysms of the anterior communicating artery]. AB - A study was performed on hydroelectrolytic changes in neurosurgical patients operated for clipping anterior communicating artery aneurysm. The patients were observed during a seven day period in ICU, between the preoperative day and the sixth post-operative day. No statistically significant changes were observed, except for hyponatriemia on the day of surgery. The etiology of this phenomenon is not clear: it could be a change of ADH or "cerebral salt wasting syndrome". A wider number of patients and repeated haematological tests are necessary. PMID- 1620466 TI - [Anuric postoperative acute renal insufficiency in neurosurgery. Importance of continuous arteriovenous hemodialysis. Report of a case]. AB - Post-operative acute oliguric renal failure was treated over a period of 17 days by continuous arterio-venous haemodialysis in man operated on for intracranial tumor. The Authors dwell on the advantages of this dialysis system in neurosurgery. PMID- 1620467 TI - [Postoperative neurosurgical complications in brain tumors operated in the elderly]. AB - 200 patients of geriatric age, operated on for cerebral neoplasm, have been studied in order to estimate the most important factors influencing the post operative course. We have considered the "Volume of the tumour", the "Pre operative and at-discharge Karnofsky Score", the possible "Pre-existent pathologies" and the checked "Post-operative complications". As a conclusion we have considered relevant over the final outcome the following factors: a) the presence of general pre-existent pathologies, first of all diabetes and hypertension; b) the volume, more than the site and nature, of the neoplasm subject of the operation; c) the nature and the importance of local post operative complications. PMID- 1620468 TI - [Postoperative complications of trans-sphenoidal surgery]. AB - One hundred and thirty three patients of both sexes were operated on for pituitary tumors with transphenoidal microsurgery. Postoperative complications are discussed. PMID- 1620469 TI - [Reduction of coronary risk using anesthesia quantified with EEG during carotid surgery]. PMID- 1620470 TI - [Effects of "new" anesthetics on intra-cranial pressure]. PMID- 1620471 TI - [Benzodiazepines and antagonists. Effect on intracranial pressure]. PMID- 1620472 TI - [Postoperative hydrocephalus. Automatic control of intracranial pressure in patients treated with external drainage]. AB - An experimental analogical device is described; it is able to stabilize the intracranial pressure (ICP) at an adjustable value in subjects exhibiting hydrocephalus. The mean ICP is measured by the intraventricular catheter, using a pressure measurement apparatus of conventional electric design. The result and two practical examples are presented. PMID- 1620473 TI - [Hyperbaric oxygen therapy in the treatment of benign intracranial hypertension. Follow-up of a preliminary study]. AB - Preliminary experience of hyperbaric oxygen (HBO) in the treatment of benign intracranial hypertension (BIH) is reported. Fifty-three patients with BIH were observed. They were treated with antiedema non steroid drugs plus rachicentesis, with steroid drugs plus rachicentesis, with lumbar peritoneal shunt and only 8 with HBO. Each patient underwent HBO with 100% oxygen at 2 atmospheres absolute a day for 15 days. In all patients a gradual disappearance of signs and symptoms of elevated intracranial pressure was observed. No lasting effect of treatment were seen after concluding therapy. The effect of HBO in the treatment of BIH has not yet been clarified, but the results can encourage further experience and studies. PMID- 1620474 TI - [The importance of monitoring the auditory evoked potentials after neurosurgery]. PMID- 1620475 TI - [Reinterventions for arterial reconstruction in anastomotic aneurysm]. AB - We reviewed our experience on the surgical treatment of anastomotic false aneurysms from 1979 through 1990: two groups of patients were identified. Group 1 (31 patients) included patients who had been previously operated on at our Institute and then routinely followed-up with physical examination and ultrasonographic studies. The incidence of anastomotic aneurysm in this group was 4.03%; the interval between insertion of the prosthesis and detection of the false aneurysm varied from 5 to 144 months, with a median interval of 58 month. The surgical treatment of choice (false aneurysm resection and graft interposition) has been successfully performed (97% of cases) without mortality. Group 2 (8 patients) included patients with complications of false aneurysm (emergency operations); in this group radical treatment was not always applicable; mortality and amputations rate were significantly increased (respectively 25% and 37%). We conclude that, after prosthetic reconstructions, only a careful long-term follow-up (also with use of ultrasonic and/or CT-scan studies) may allow reduction in morbidity and improvement in late survival. PMID- 1620476 TI - [Femoral non-infected anastomotic pseudoaneurysm. Clinical contribution]. AB - The femoral region is the most common site of development of anastomotic pseudoaneurysms that represent a relatively frequent complication of reconstructive vascular surgery. Clinical examination alone generally is sufficient to diagnose these lesions because they usually appear as a pulsatile inguinal mass not accompanied by pain. Echography and angiodynography permit a better evaluation of size and blood flow. CT is useful to evaluate proximal aortic anastomosis specially in pseudoaneurysms with septic pathogenesis. Rupture or thrombosis are rare clinical presentations. Vascular reconstructive surgery is always suggested in this sort of pathology. In this paper the Authors report the clinical experience acquired from 1980 to 1990 in the General and Cardiovascular Surgery Department of the University of Milan (Head: Prof. Ugo Ruberti) is 34 cases of femoral anastomotic aseptic pseudoaneurysms, analyzing the pathogenesis of this sort of lesion, describing the surgical solutions adopted and reporting the immediate and late results. PMID- 1620477 TI - [Asymptomatic lithiasis of the common bile duct: diagnostic difficulty and essentiality of intraoperative cholangiography]. AB - Biliary lithiasis is a widespread pathology the diagnosis of which, following the introduction of ultrasonography, is increasingly easy. The frequent possibility of association between gallstones and choledocholithiasis, demands pre- or intraoperative recognition. The inadequacy of ultrasonography in excluding lithiasis of the common biliary tract with certainty, notwithstanding its other unquestionable advantages, and the disproportionate costs and risks of other investigations (cholangiography, ERCP, ecc.) which are such as to discourage routine use, confirm the role of operative cholangiography in the diagnosis of asymptomatic choledocholithiasis, so permetting its treatment. Personal experience of 100 consecutive cases of gallstones which showed fully 10 of them to be negative to preoperative investigation were found to have lithiasis of the common biliary tract. PMID- 1620478 TI - [Postoperative morbidity and mortality in patients undergoing additional cholecystectomy during digestive surgery]. AB - A retrospective case-control study was carried out to assess whether additional cholecystectomy in patients undergoing digestive surgery caused increased postoperative morbidity and mortality. During the period 1983-90, 70 patients underwent cholecystectomy at the same time as other surgery (25 gastric resections, 23 colon resections, 17 total gastrectomies, 2 fundoplicatio using Nissen's technique, 2 cases of Heller's operation, 1 truncular vagotomy and pyloroplasty). These cases were matched for sex, age (+/- 5 years) and type of primary operation with 70 controls (patients without additional cholecystectomy). Complications were significantly more frequent among the former group compared to controls (28.6% vs 11.4%, p = 0.02), in particular in the group of patients undergoing colon resection (34.8% vs 8.7%, p = 0.04). The frequencies of reoperation and mortality were also higher in patients undergoing additional cholecystectomy than in controls (10% vs 1.4%), but the difference was not statistically significant (p = 0.06). In conclusion, additional cholecystectomy during digestive surgery increases the risk of postoperative complications, in particular in colorectal surgery. PMID- 1620480 TI - [Loco-regional anesthesia in ambulatory surgery]. AB - Following a brief review of the various types of local anesthesia, including a recent method using EMLA cream, the paper focuses on the different complications which arise in relation to the technique used. Treatment protocols are also analysed in relation to the toxic stage. PMID- 1620479 TI - [Non-epithelial benign gastric neoplasms]. AB - The Authors report five cases of benign neoplasm of the stomach: 2 leiomyoblastomas, 2 leiomyomas and 1 ganglioneuroblastoma, underlining its rarity. After a review of the literature, the anatomo-pathological, clinical and therapeutical findings are described. The difficulty of early diagnosis is underline and the need for surgical therapy states. PMID- 1620481 TI - [A difficult diagnosis: retroperitoneal rupture of the duodenum caused by closed trauma of the abdomen]. AB - The Authors report two cases of sub-peritoneal rupture of the duodenum following blunt abdominal trauma. The diagnostic difficulties are explained in detail. Emphasis is placed on the importance of prompt recognition of the duodenal injury and early surgical treatment to ensure a successful outcome. PMID- 1620482 TI - [Persistent multiple urachal complex. Echographic-surgical correlations]. AB - Urachus is a tubular structure lined between foetal bladder and the umbilicus and is susceptible to complete or partial involution after birth. Persistence of the urachus results in a wide spectrum of anomalies: patent urachus, vesicourachal diverticulum, urachal sinus and cysts are more frequently seen than rare multiple urachal remnants. This kind of pathology focuses the problem of differential diagnosis (tumours, omental and ovarian cysts, vesical diverticulum or duplication) and may be complicated by a superinfection. The Authors discuss a bizarre multiple urachal remnant, presenting with urinary tract symptoms, which may be clinically confused with acute appendicitis or Meckel's diverticulitis. Contribution of sonography for a complete diagnosis is stressed, such as the precise correlation with surgical findings. PMID- 1620483 TI - [A case of retroperitoneal leiomyosarcoma]. AB - Leiomyosarcoma is a rare malignant tumour originating from the smooth muscular tissue in any part of the organism, including retroperitoneum where it is particularly aggressive. It is nearly always characterized by a silent development causing diagnostic delay. The results of the primary therapy, which is always surgical, are limited because of the tumoral mass extension and the high local aggressiveness. The Authors present a clinical case which was under their observation and seize the opportunity of making a revision of the literature about it. PMID- 1620484 TI - [A case of intestinal occlusion caused by malignant ileal lymphoma]. AB - The Authors review a case of intestinal non-Hodgkin lymphoma, whose clinical feature was an intestinal obstruction caused by ileoileal intussusception. Some findings which make it unusual are compared with those mentioned in the international literature. PMID- 1620485 TI - [Elastofibroma of the back. Considerations on 2 cases]. AB - Two cases of fibroelastoma of the back are reported. It is pointed out that probability diagnosis in mainly entrusted to the objective examination and to the typical site of tumefaction, backed by echotomography, xeroradiography and computerised tomography and demonstrated by histological examination of the operative piece. Differential diagnosis has to be established versus fibrosarcoma, liposarcoma, desmoid tumour and malignant tumour of the synovia. The need for surgical removal is reiterated. PMID- 1620486 TI - Dunston and Riggs call for HIV testing. PMID- 1620487 TI - Chronic steroid dependent asthma. PMID- 1620488 TI - The silicone bust. PMID- 1620489 TI - What about Prozac? PMID- 1620490 TI - Applications of MRI for diagnosis of cardiovascular diseases. AB - Magnetic resonance imaging (MRI) acquires high spatial resolution images of the heart from any part of the cardiac cycle and in any planar configuration without use of contrast. Sequential images through the cardiac cycle can be viewed as a cine. PMID- 1620491 TI - OSHA knocking on doctors' doors. AB - New regulations by the Federal Occupational Safety and Health Administration require every medical office to train staff, offer hepatitis vaccinations, and impose universal precautions. An "occupational exposure control plan" is required of every office. PMID- 1620492 TI - SBME overhauls health care delivery structure. AB - SBME requires office manuals and additional paperwork, and limits dispensing of drugs and medical equipment. Multispecialty facilities with physicians and other health care professionals are permitted in the same professional corporation, with private investors funding the company. PMID- 1620493 TI - Angucycline group antibiotics. PMID- 1620495 TI - The biosynthesis of shikimate metabolites. PMID- 1620494 TI - The microbiological transformation of diterpenoids. PMID- 1620496 TI - New Zealand suicides 1984-8. AB - AIMS: to determine regional differences in suicide with special attention to inpatients and prisoners. METHODS: all cases of suicide 1984-8 were identified from coroners' register and age, sex, method of suicide, date of death, place of inquest, occupation and prisoner or inpatient status were recorded. RESULTS: between 1984 and 1988 there were 2019 suicides. Subjects were usually male and hanging was the commonest method of achieving death. Northland-Auckland had the highest regional suicide rate and the highest prison suicide rate; and Wellington Wairarapa had the lowest regional suicide rate, the lowest prison suicide rate but the highest inpatient suicide rate of the five regions studied. CONCLUSIONS: the high regional and prison rates of suicide in Northland-Auckland were probably because the largest city in New Zealand lies within its boundaries. The high inpatient suicide rate in Wellington-Wairarapa could not be explained by the regional rate, nor by controlling for the number of admissions. This pointed to regional differences in the delivery of psychiatric care. PMID- 1620497 TI - The relationship between body mass index and socioeconomic status in New Zealand: ethnic and occupational factors. AB - AIMS: the relationship between body mass index (BMI) and socioeconomic status (SES) was examined in a multiracial New Zealand workforce in order to investigate ethnic variations. METHODS: an employed population of 5673 people were measured for weight and height and BMI calculated. Socioeconomic status was assigned using the UK Registrar General's scale. RESULTS: both European women and men showed an inverse relationship of increasing BMI with decreasing SES which is typical of developed societies. Maori, Pacific Islanders and Asians did not, but neither did they show the direct relationship of developing societies. Examination of the components of SES showed that combined family income did not influence BMI in any ethnic group but that education was strongly associated with BMI in Europeans (p = 0.0001) and weakly associated in Maori (p = 0.0603), and occupation was strongly associated with BMI in Europeans (p = 0.0001) and weakly associated in Pacific Islanders (p = 0.0148) independently of education. CONCLUSIONS: ethnic variations are partly explained by educational levels and occupation, but not by income. Increased education may decrease prevalence of obesity. Some occupational factors are discussed. PMID- 1620498 TI - The place of ultrasound imaging in pregnancy. PMID- 1620499 TI - Changes in sexual practices and some HIV related attitudes in New Zealand: 1987 9. AB - Two fully national samples of 1000 New Zealanders aged 16-60 were interviewed in 1987 and in 1989 about their sexual practices and related attitudes to HIV/AIDS matters. The data were gathered by means of a self completed questionnaire which was part of a larger interview undertaken in the respondents' own homes. Precautions were taken to ensure confidentiality, anonymity and privacy. There were significant differences in the reporting of sexual behaviour during the two year study period. The proportion of the sexually active reporting three or more sex partners in the previous year fell from 12% to 8%. The proportion reporting "always" or "often" using condoms rose from 13% to 18% and those reporting permanent changes to sexual behaviour because of AIDS rose from 16% to 26%. Changes towards safer sexual practices were more common amongst males, the young, the unmarried and those with multiple sex partners. Findings concerning attitudes to HIV/AIDS related matters showed an increase in the population's perceived risk of the virus to both themselves and others. For example the proportion who felt everyone was at risk rose from 71% in 1987 to 80% in 1989. There was also evidence of increased victim blaming of the person who caught HIV infection or other sexually transmitted diseases. Finally there was evidence of the need for more action on AIDS. In 1987 35% felt that enough was being done whereas this had dropped to 27% by 1989. PMID- 1620500 TI - The costs of smoking revisited. AB - AIMS: a previous study of the cost of smoking to the New Zealand health services estimated that the excess hospital resource use generated by smoking amounted to $81 million in 1986 dollars. The present study refined and updated the figures for hospital resource use, and extended the costing exercise to include aspects of primary health care. METHODS: excess hospital costs attributable to smoking were estimated from the 1987 national hospital discharge data (both public and private hospitals), and figures obtained from the Otago resource utilisation system (RUS). The costs of excess prescription medicines use and general practitioner consultations were estimated from existing data sources. RESULTS: the excess hospital costs attributable to smoking totalled $128.3 million. A further $37.8 million was consumed in excess prescription medicines use, plus $19.3 million in general practitioner consultations. The total cost to the health services of cigarette smoking was therefore conservatively estimated at $185.4 million (in 1989 dollars). CONCLUSIONS: previous estimates substantially underestimate the external costs imposed by smoking. The figure of $185.4 million contrasts with the $7.5 million of sponsorship support which the tobacco industry is estimated to provide for New Zealand sports. Politicians who intend to repeal Part 2 of the Smokefree Environments Act (1990) should consider these external costs imposed on society by cigarette smoking. PMID- 1620501 TI - Intermittent supervised treatment of tuberculosis at Green Lane Hospital, 1987-8. AB - AIMS: to assess the results of the first two years experience with intermittent supervised treatment of tuberculosis (IST) in Auckland, looking especially at practical problems. METHOD: the hospital records of the 16 patients who received IST during 1987-8 were reviewed retrospectively, and public health nurses who administered the medications were questioned about problems that were encountered. RESULTS: two-thirds of those who were given IST were Polynesian. In retrospect, the need for IST could have been anticipated in eight of the 12 patients (67%) who failed to comply with daily treatment. Five of the 16 IST patients presented major problems to the nurses supervising the twice weekly treatment. Poor motivation, itinerancy and alcohol abuse were the most common factors causing difficulty. IST was successfully completed in 13/16 patients (81%) and was abandoned in only one patient. Only two patients completed IST with a drug regimen for resistant organisms. Health nurse supervision resulted in improvements in understanding and attitude to tuberculosis, eventually enabling two patients to self medicate without supervision. CONCLUSIONS: IST is a practical treatment method in New Zealand, permitting curative therapy in a group of tuberculosis patients who would otherwise create risks of drug resistance, disease reactivation and spreading the disease. PMID- 1620502 TI - Sea anemone sting while SCUBA diving. PMID- 1620503 TI - Giant T wave inversion. PMID- 1620504 TI - Urinary tract infections in adults: Part 2--Prophylactic regimens of treatment. PMID- 1620505 TI - Cot deaths. PMID- 1620506 TI - Campylobacter infection 1991. PMID- 1620507 TI - Cost effectiveness of treatments for alcoholism--you can't compare apples with cabbages. PMID- 1620508 TI - Effects of a physical conditioning programme on asthmatic patients. AB - AIMS: to determine whether moderate/severe asthmatics can improve their physical fitness using standard commercial gymnasium fitness programmes and to examine the effect on their asthma. METHODS: eight moderate to severe asthmatics and seven nonasthmatic controls were tested before and after 12 weeks indoor circuit training at a commercial gymnasium. The aerobic fitness of both groups was assessed before, during and after the conditioning period. Measures of asthma severity, habitual activity levels and psychological status were also assessed. RESULTS: peak oxygen uptakes increased significantly in both asthmatics and controls, mean and 95% confidence interval (95% CI) values rising from 27.5 (21.9 33.0) to 31.3 (23.5-39.1) and 29.2 (25.9-32.5) to 32.2 (28.5-35.9) mL.min-1.kg-1 respectively. Following training, minute ventilation at high workloads was significantly reduced in the asthmatic subjects. In all participants subjective ratings of the ability to perform physical tasks was significantly increased as was the amount of habitual physical activity reported. Although the asthmatics' bronchial responsiveness to histamine, medication usage and symptom scores did not change, the daily recorded peak expiratory flow (PEFR) increased slightly, and its variability declined. CONCLUSIONS: these findings demonstrate that with proper management severe asthmatics can engage in vigorous circuit training and enjoy the health benefits of regular exercise. PMID- 1620509 TI - Carcinoma of the glottic larynx: the Christchurch experience. AB - AIMS: to establish the local control and survival rates for glottic laryngeal cancer, and to determine the incidence of second primary cancers after treatment of the original tumour. METHODS: a retrospective review of all patients with glottic cancers treated in Christchurch over a five year period, with a minimum follow up of five years. RESULTS: between 1979 and 1984, 83 patients with laryngeal cancer were treated in Christchurch Hospital. Forty-seven of these patients had cancers of the glottic larynx. Overall, 39 of 45 patients were free of their laryngeal cancer at five years (two were lost to follow up). Eight of 45 developed a second primary cancer, usually lung or oesophagus, and this was invariably fatal. CONCLUSION: with multidisciplinary management of head and neck cancers satisfactory control rates can be achieved, but since these patients are usually heavy smokers and drinkers, they are at high risk of developing a second primary cancer. The use of chemopreventative agents is mentioned. PMID- 1620510 TI - A testing time for heart disease. PMID- 1620511 TI - Condom use in anal intercourse amongst people who identify as homosexual, heterosexual or bisexual. AB - AIMS: to study condom use amongst those who practice anal intercourse. METHODS: a sample of 814 clients attending anonymously for pretest counselling for HIV infection at the Burnett Clinic, Auckland, gave detailed information about their sexual behaviour. RESULTS: insertive or receptive anal intercourse was reported in 39% of clients. This included 89% among homosexual men, 78% among bisexual men, 17% among heterosexual men and 21% among heterosexual women. In those practising anal intercourse concomitant condom use was reported by 71% of homosexual men, 53% of bisexual men, 16% of heterosexual men and 7% of heterosexual women. Those most likely to use condoms were homosexual men, prostitutes, those with multiple partners and those with an HIV infected partner. Those least likely to use condoms were heterosexual men or women. CONCLUSIONS: whilst substantial changes in sexual practices appear to have been made in the homosexual community, heterosexuals practising anal intercourse have made few such changes. More explicit AIDS education may be necessary which acknowledges that anal intercourse is practised by heterosexuals and advises condom use accordingly. PMID- 1620512 TI - Asthma knowledge and management in primary schools in south Auckland. AB - AIMS: to examine the management of asthma in primary schools and the school teachers' knowledge, confidence and attitude in managing the pupils with asthma. METHODS: forty-two primary schools in south Auckland were randomly selected to participate. Questionnaires were posted out to the principals and another questionnaire was given randomly to 253 teachers from these primary schools. RESULTS: 76% of the school principals surveyed returned the questionnaire; and 66% of the school teachers surveyed returned a separate questionnaire. The average incidence of asthma reported by school principals and school teachers was 9.9% and 12.6% respectively, which suggests underreporting of the diagnosis of asthma. In 81% of the schools a questionnaire was used to identify students with asthma when they first join the school. School teachers had good basic knowledge on asthma, however 33% of teachers did not know that Ventolin (salbutamol) is for symptomatic treatment and 58% and 65% of teachers did not know that Becotide (beclomethasone) and Intal (sodium cromoglycate) are prophylactic medications. CONCLUSIONS: we suggest that primary school teachers should receive further education on asthma, especially on practical aspects of asthma management. PMID- 1620513 TI - A clinical audit of patients on an orthopaedic waiting list for greater than two years. AB - AIMS: the aims of this paper were to review a group of 142 patients who had been on an orthopaedic waiting list for more than two years, both by postal audit and by clinical assessment, and to determine the fates of these patients. METHOD: all patients who had been on the orthopaedic waiting list for more than two years were written to, asking them to attend a preadmission clinic if they still required surgery. Those who attended the clinic were reassessed with regard to their orthopaedic problem and general state of health. Preadmission summaries, radiographs and waiting list details were analysed with respect to time spent on the waiting list, changes in clinical and radiographic findings and changes in diagnosis or proposed operation. The number of patients removed from the waiting list and the reason for removal was noted. RESULTS: One hundred and thirty-four of 142 patients replied. One hundred and three attended the preadmission clinic. A change of diagnosis was made for four patients and nine patients underwent a different operation than that originally proposed. Thirty-four patients were removed from the waiting list after reassessment. Of the 142 original patients only 69 (49%) remained on the waiting list. A number of patients deteriorated significantly while on the waiting list. CONCLUSION: a significant number of patients on a long orthopaedic waiting list may no longer require surgery. A number of patients can be expected to deteriorate significantly while on the waiting list. Postal audits alone are insufficient to determine who on the waiting list still requires surgery. PMID- 1620514 TI - Varicose vein avulsion incisions: any need for sutures? PMID- 1620515 TI - New Zealanders--why let this medical experiment proceed? PMID- 1620516 TI - The National Women's Hospital settlement. PMID- 1620517 TI - Unaware hypoglycaemia and human insulin. PMID- 1620518 TI - Insulin resistance and hypertension. PMID- 1620519 TI - Iron deficiency. PMID- 1620520 TI - Early results of endometrial resections using a simple criteria for patient selection. PMID- 1620521 TI - Getting the figures right. PMID- 1620522 TI - Hearing damage from a cordless telephone. PMID- 1620523 TI - Treatment for gardnerella vaginitis. PMID- 1620524 TI - Technique for total abdominal hysterectomy: historical and clinical perspective. AB - Since the first refined total abdominal hysterectomy was performed by Wilhelm Alexander Freund of Breslau on January 30, 1878, various techniques have been introduced over the past 110 years. Hysterectomy, numbering over 650,000 procedures annually, is the most commonly performed major surgical procedure next to cesarean section in the United States. Although CREOG (Council on Resident Education in Obstetrics and Gynecology) emphasizes the importance of basic pelvic surgical skills and competency in gynecological surgical procedures, cost effective patient management dictates the shortest hospitalization and most uncomplicated procedure possible. Various techniques of abdominal hysterectomy have been reappraised in view of present-day medical practice concepts. It seems that we are entering a new age wherein a simplified, cost-effective alternative to a classical total abdominal hysterectomy is indeed needed for some cases, and if a hysterectomy is planned, it should be performed in the safest way in the shortest possible operating time for a well-indicated case. Keeping this objective in mind, one Japanese technique of total abdominal hysterectomy and its modification are described with the intent that this will assist Ob/Gyn resident physicians in surgical skill development and also help gynecologists in practice to meet rapidly changing practice patterns of the specialty. PMID- 1620525 TI - A review of the microbiology, immunology, and clinical implications of Chlamydia trachomatis infections. PMID- 1620526 TI - A macroscopical study of the inferior phrenic artery of female rats, with reference to the embryological background of occurrence of the genital artery from this artery. AB - The principal aim of this study was to elucidate the general features of the inferior phrenic artery (IPA) of female rats which retain the original embryonic configuration of this artery. The artery of the right side was found to be detached from the renal artery, while that of the left side arose from the aorta. Between these fellow arteries, however, no essential morphological differences were discernible. At some point not far from their origin, they were found to break up into the ascending, suprarenal, suprareno genital and descending arteries. The ascending artery of the right side coursed along with the phrenic nerve, and vascularized a greatest portion of the total area of the partes sternalis et costalis of the diaphragm. Furthermore, the artery was found to be intimately associated with the inferior caval vein. Thus, it could be assumed that this artery of adult rats has been embryologically related to the musculus diaphragmaticus, transverse septum, ventral pleuroperitoneal fold, and the caval venous mesentery. The suprarenal artery took its course along the superior margin of this gland to reach the lateroinferior part of the pars costalis of the diaphragm. Its course and destination strongly indicates that in its development the suprarenal artery has been intimately related to the formation of the ventral pleuroperitoneal fold. The suprarenogenital artery was characterized as giving off a genital branch which entered first the diaphragmogenital ligament, and then took a descending course toward the ovary, in a quite similar manner of origin and course to those of the aberrant gonadal (testicular and gonadal) arteries observed in Japanese human adults (Shinohara et al., 1990; Hanie, to be published). The descending artery was observed to be closely associated with the major splanchnic nerve and the celiac ganglion. The variability of arteries of the IPA of female rats and also of humans, seems to reflect dramatic changes which have occurred in the early stages of development, and have influenced more or less the morphology of the uppermost abdominal anlages of the followings: transverse septum, musculus diaphragmaticus, dorsal and ventral pleuroperitoneal folds, suprarenal gland and celiac ganglion, urogenital organs, inferior caval vein in the caval venous mesentery. In conclusion, it could be said that the anatomy of female rats provide us valuable clues as to the essential configuration of the IPA of humans and the relationships of the IPA to structures which are thought to be directly involved in the development of this artery. PMID- 1620527 TI - The first capitular joint in primates: Cebidae, Cercopithecidae and Homo. AB - As for the first capitular joint, Ohman (1986) claimed that a univertebral type is unique to modern and fossil hominids among primates. Stern and Jungers (1990) compiled the data in a wider range of primate and demonstrated as follows. The univertebral type, rather than being unique to hominids, is common among siamang, occurs in an occasional gibbon, and is typical of the larger indriids. We added the data of genera of Cebidae and Cercopithecidae to that observation, and found that the univertebral type is also typical of the Pithecia in Cebidae and Papio and Cercopithecus in Cercopithecidae. We also found that the bivertebral type occurs in 19.4% of Homo. Gloobe and Nathan (1970) had already observed that most mammals have a full facet for the first rib and a hemifacet for the second in the first thoracic vertebra. Accordingly, it seems that Ohman's claim is not applicable for nonhominoid primates and for mammals. PMID- 1620528 TI - Histological and histochemical investigations on Japanese lizard esophagus. AB - The authors previously investigated the bottle-shaped glands distributed in the lamina propria mucosae of the Japanese lizard and gecko. We made two sets of sections of the Japanese lizard at that time. The numerical values of the physical dimensions of the two individuals were as given table 1, showing that No. 2 was slightly smaller. Moreover we found very unusual tissue in the lower portion of the esophagus of No. 2. Therefore we excluded this individual from the preceding investigations. However, we made various observations, and the results of these investigations are as follows. 1. The lumen of the upper portion of the esophagus has no fold. However, the middle and lower portions formed very complicated folds. Therefore, the lumen was remarkably narrow. 2. The epithelium of the esophageal mucous membrane consisted of simple columnar cells and throughout each part, reacted strongly to PAS and moderately to AB (pH 2.5 and 0.5). It presented a dark blue (R18-B13 of Blue-Purple-Red) color in response to PAS-AB (pH 2.5) and contained no pepsinogen granules. The esophageal upper portion of small individuals only exhibited the PAS reaction in this investigation. 3. A number of bottle-shaped glands were distributed in the lamina propria mucosae of the lower portion of the esophagus of each material. The glandular cells in the basal portion were most differentiated and contained a great number of pepsinogen granules. 4. The above-mentioned glands were extremely simple and glands of this type could not be found in textbooks and theses. Accordingly, we previously described them with the tentative name of shimple branched tubular glands, but subsequently found this to be erroneous. We assume that these glands are esophageal gastric glands. 5. Compound tubular glands are formed in the lamina propria mucosae of the human esophagus, but do not exist in the Japanese macaque, crab-eating monkey, horse, cow, swine, dog, cat, rabbit, mouse and rat. Dellmann-Brown also described the absence of such glands in the esophagus of the horse, swine, cow, goat, sheep, dog and cat. 6. We subsequently found compound tubular glands distributed in the lamina propria mucosae of the fowl, goose and wild duck esophagus. They similarly secreted pepsinogen granules. 7. We assume that these glands of the Japanese lizard and gecko have a phylogenic relation with the glands in the bird. The pepsinogen-granule-secreting cells in the snake do not extend into the lamina propria mucosae.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1620529 TI - On the organization of the Plexus lumbalis. I. On the recognition of the three layered divisions and the systematic description of the branches of the human femoral nerve. AB - The arrangement of the nerve bundles at the branching point of the femoral nerve (F), the interrelations of the branches each other and toward other nerves in the anterior region of the thigh, and the patterns and the anatomical features of both the running courses and the distributions of the branches were macroscopically studied, whereby some special findings were observed and the following results were obtained: 1) The periphery of the femoral nerve was fundamentally divided into superficial-deeply arranged three-layered divisions. Including the femoral branch of the genitofemoral nerve (Rf) and the femoral lateral cutaneous nerve (Cfl), the nerve branches at the anterior region of the thigh were totally divided into five-layered divisions. 2) The cutaneous branches of each division including Rf or Cfl could be classified in three groups: the medial cutaneous branches (m), the anterior cutaneous branches (a), and the lateral cutaneous branches (l). Based on the above results, the branches could be described systematically. Parallelly, several accessory bundles of F penetrating the psoas major muscle were observed, and two types of accessory femoral nerves (F') could be distinguished: One was higher on the segmentation and mainly flew into the 1st division of F. While the other distributed only to the medial region of the thigh. To clarify the segmental or stratifical natures of the branches of each division, F', and the interrelations among them, analyses of the nerve fibers were undertaken under the operational microscope. Consequently, the segmental differences between the divisions were distinct, and the medial branches or F'm obviously contained ventral components. Thus, when a component originated from the higher segments, it distributed to the proximal region generally taking a superficial course; when it originated from the lower ones, it distributed to the distal region of the thigh forming the deeper division; when it belonged to the ventral stratum, it distributed to the medial region; and when it belonged to the dorsal stratum, it distributed to the lateral region. On the occasion of the fiber analysis, it was found that each root of the lumbar nerve was generally divided into two or three subsegmentally-arranged subroots that divided themselves into some fasciculi arranged micro-segmentally. A minute analysis of the segmentations of the nerves became possible because of the above characteristics. PMID- 1620530 TI - A silver impregnation method for neurons in the central nervous system of the small laboratory animals. AB - Brains of small, adult laboratory animals, fixed by formalin-perfusion, and cut into pieces usually 2-3 mm thick X 3-5 mm2 are placed into a solution containing: 7% aqueous solution of potassium dichromate 100 ml, 99.5% ethyl alcohol 40 ml, concentrated formalin 10 ml, distilled water 50 ml, for 24 hours. The process is repeated with a freshly prepared solution for another 24 hours. The pieces are then transferred to a 3.5% aqueous solution of potassium dichromate for 48 hours, and then to a 1% aqueous solution of silver nitrate for 48 hours. Frozen or celloidin sections 70-100 microns in thickness are put into 90% and then into 100% ethyl alcohol for 30 minutes respectively, creosote-benzene (1:1), benzene and mounted with or without cover glass applying Entellan neu. This procedure gives high quality impregnation and it takes about one week to complete. PMID- 1620531 TI - The degenerative neck. PMID- 1620532 TI - Natural history and pathogenesis of cervical disk disease. AB - As the cervical spine ages, degenerative processes occur that involve the intervertebral disk as well as facet joints. Some individuals experience pain as this process evolves. In many instances, it can be difficult to correlate a patient's symptoms with the associated changes. This article reviews the appropriate anatomy and biochemistry of the cervical spine and presents the pathologic entities that are encountered. PMID- 1620533 TI - The syndromes of degenerative cervical disease. AB - Senescence of the cervical spinal motion segment is manifest by changes in each anatomic component. The pathoanatomical change that predominates varies from one person to the next. Sufficient compromise of local neural structures will precipitate the onset of symptoms. The pattern of symptoms and any associated physical signs will vary according to which structures are stimulated or compressed. Radicular and myelopathic syndromes are produced by nerve root and spinal cord compression, respectively. These patterns can occur individually or in combination. Other less clearly understood patterns of local and referred symptoms may be mediated by the sinu-vertebral nerves or the medial branches of the posterior ramus. Techniques for the precise diagnosis of these syndromes are needed. Separating patterns of symptomatic degenerative cervical disease from other causes of neck, shoulder, and arm symptoms rests on an awareness of the broad spectrum of subjective complaints, a thorough physical examination, and confirmatory diagnostic studies. Clear delineation of the etiology will increase the likelihood of successful treatment. PMID- 1620534 TI - Radiographic evaluation of the degenerative cervical spine. AB - Despite some claims to the contrary, the use of plain film radiography can be an inexpensive initial means of evaluating the degenerative cervical spine if viewed in the context of the patient's clinical history and physical examination and may serve as a guide for further imaging techniques. This article presents a systematic approach for evaluating cervical spine radiographs for the spectrum of degenerative changes, followed by a brief discussion of differential diagnoses. PMID- 1620535 TI - Diagnosis of nerve root compression. Myelography, computed tomography, and MRI. AB - Current technology and published studies support the preferential use of MRI in the diagnosis of cervical myelopathy. In cervical radiculopathy, data support the use of either contrast-enhanced CT or MRI. We prefer MRI as the initial diagnostic test because of the obvious advantage of its noninvasive nature. Similar to myelography, MRI permits visualization of the entire cervical canal and spinal cord. Unlike routine CT, MRI visualizes the spinal cord and nerve roots in two planes and is better in detecting unsuspected pathology at other cervical segmental levels. Because the quality of MRI scans in the cervical spine is subject to more variation than in the lumbar spine, anticipated pathology is sometimes not clearly visualized by cervical MRI. Under such circumstances, we obtain a water-soluble myelogram followed by contrast-enhanced CT. Because inaccurate radiographic diagnosis is one of the identifiable causes of poor outcome in surgical therapy for cervical spondylosis, accurate visualization of pathology in terms of its location, nature, and extent is imperative before performing decompressive cervical spine surgery. PMID- 1620536 TI - Analysis of medications used in the treatment of cervical disk degeneration. AB - This review focuses on the scientific design and concepts of drug management of cervical disk disorders. Steroids, nonsteroidal anti-inflammatory medicines, narcotics, antidepressants and muscle relaxants are discussed. PMID- 1620537 TI - Role of physical therapy in the treatment of cervical disk disease. AB - Table 4 summarizes how physical therapy should be implemented during the acute and chronic phase of cervical disk disease. From the outset of treatment, the patient should be encouraged to return to work or other productive activities and should be taught how to be responsible for their own recovery. If passive modalities are used, they must be an adjunct to the active modalities. As soon as the patient is able to continue with an active program without unbearable pain, the passive modalities should be discontinued gradually. If neck pain becomes chronic, the accompanying psychosocial dysfunction must be addressed through behavioral modification techniques, preferably in a multidisciplinary setting. Modification of the work place, work habits, and lifestyles must be emphasized at both the acute and chronic stages. The modalities presented in this article are commonly used by physical therapists. Unfortunately, the clinical efficacy of most of these modalities has yet to be proved. A literature search on the effectiveness of various physical therapy modalities by Sievers et al showed that only 4% of the studies published from 1979 to 1985 were controlled clinical trials. This scientific output of physical therapists needs to be corrected. PMID- 1620538 TI - Surgical management of cervical radiculopathy. Indication, techniques, and results. AB - Cervical radiculopathy can be surgically approached either posteriorly or anteriorly and the anterior approach has been described with or without fusion. The choice of approach and technique must be based upon anatomic, pathophysiologic, and biomechanical principles in addition to the familiarity of the surgeon with the procedures. The authors discuss the use of the posterior approach for lateral soft-disk disease because it minimizes disruption of soft and bony tissues and does not markedly disrupt the biomechanics of the cervical spine. The anterior approach is preferred for radiculopathy involving osteophytic hard-disk disease, and when properly and carefully performed, the addition of an interbody fusion holds significant advantages over diskectomy without fusion. PMID- 1620539 TI - Types of anterior cervical grafts. AB - Anterior cervical diskectomy and fusion provide satisfactory results in most instances of cervical disk herniation and cervical spondylosis. A variety of interpositioned grafts have been described for such problems at one or two levels. Multiple level anterior decompression and fusion for patients with spondylotic myelopathy produce satisfactory results in most instances and are particularly effective when a degenerative kyphosis is present. Appropriate patient selection and attention to technical aspects of exposure, neural decompression, and graft procurement and placement directly influence the surgical outcome. PMID- 1620541 TI - Surgical management of myelopathy. AB - We have presented a comparative analysis of the ability of four surgical procedures to address adequately the problems sustained by a patient with symptomatic cervical myelopathy. AIA is a safe procedure whose effectiveness may be limited when the extent of disease is more than three intervertebral disk levels. ACA permits more direct and extensive access to the spinal cord and is the procedure of choice for cervical spondylotic myelopathy associated with spinal deformity. However, rigid external immobilization is necessary, and operative morbidity may be greater. Cervical laminectomy may be effective for decompressing the spinal cord when no associated spinal deformity or instability is present, provided that extensive resection of facet joints is avoided. Cervical laminaplasty is ideally suited for the patient with three or more levels contributing to a cervical myeloradiculopathy. Mild instability may be addressed by performing arthrodesis on the hinge side. PMID- 1620540 TI - Cervical spondylotic myelopathy. Clinical syndrome and natural history. AB - A wide-based spastic gait is the classical presentation of the patient with cervical spondylotic myelopathy. A complete neurologic evaluation is needed to determine the degree of involvement and to classify the clinical syndrome. The natural history seems to be one of static neurologic deficit or episodic progression. PMID- 1620542 TI - Postlaminectomy kyphosis. Causes and surgical management. AB - Postlaminectomy instability of the cervical spine can be managed either anteriorly or posteriorly. The posterior procedures that have been described are best performed at the time of the original decompressive procedure. Thus, the development of a kyphotic deformity is prevented. Generally, it is technically easier to achieve anterior stabilization and arthrodesis if a postlaminectomy kyphosis develops. PMID- 1620543 TI - Two antisense promoters in the immunoglobulin mu-switch region drive expression of c-myc in the Burkitt's lymphoma cell line BL67. AB - In the Burkitt's lymphoma (BL) cell line BL67 the first exon of the c-myc gene is fused to the mu-switch region of the immunoglobulin heavy-chain gene (IgH). BL67 cells express IgH/c-myc hybrid RNAs which are initiated in the immunoglobulin locus, transcribed across the chromosomal breakpoint into the first exon of c-myc and spliced using the physiological splice donor and acceptor sites of the c-myc gene. We have isolated cDNAs of these hybrid RNAs and characterized the start points in the Ig heavy-chain gene. Two promoters were identified in the mu-switch region of BL67 cells which give rise to antisense transcription of the mu-gene. These promoters are also active in other BL cell lines, in B cells without Ig translocation and in a T-cell line. Both promoters co-localize with DNAase I hypersensitive sites, HNF and HSW, in the mu-switch region. The structures of IgH/c-myc hybrid RNAs and of the corresponding promoters are described. PMID- 1620544 TI - The ras and protein kinase A pathways are mutually antagonistic in regulating rat prolactin promoter activity. AB - In an attempt to characterize the ras signaling pathway, we studied the effects of expression vectors encoding the valine 12 mutant ras oncogene on rat prolactin (rPRL) promoter activity. Using this approach we have been able to dissect the interplay between the ras and the protein kinase A (PKA) pathways as they relate to neuroendocrine gene activation. Here we show that the ras oncogene product induces rPRL promoter activity selectively from 5- to 14-fold in GH4 rat pituitary tumor cells, whereas it has a minimal effect on the SV40 early promoter and no effect on the Rous sarcoma virus (RSV) or rat growth hormone promoters. By contrast, an inactivated form of ras (N-17 ras) did not stimulate the rPRL promoter, but rather inhibited it to 40% of control. Of note, activation of the PKA pathway by two different methods decreased the fold activation mediated by ras by at least 50%, whereas inhibition of the PKA pathway accentuated ras activation of the rPRL promoter. Although rPRL promoter activity is consistently induced by PKA activation in control GH4 cells, acute ras oncogene expression inhibited forskolin induction of rPRL promoter activity. Moreover, this ras mediated interference of the forskolin activation of rPRL promoter activity was also noted in GH4 cells stably expressing ras. Taken together, these data show that the valine 12 ras oncogene activates the rPRL promoter selectively and, more importantly, that the ras and PKA signaling pathways are mutually antagonistic with respect to specific transcriptional activation of a neuroendocrine gene. PMID- 1620545 TI - Dependence of SV40 large T-antigen cell cycle regulation on T-antigen expression levels. AB - Simian virus 40 (SV40) large T antigen (Tag) expression results in reduced percentages of G1-phase cells and increased percentages of S- and G2+M-phase cells in exponentially growing fibroblast populations as compared with identical cell populations not expressing Tag. This effect is the result of reduced G1 and increased G2+M cell cycle phase durations caused by Tag [Sladek, T.L. & Jacobberger, J.W. (1992). J. Virol., 66, 1059-1065]. Using recombinant retroviruses to manipulate Tag expression over a 25-fold range, it is shown here that the magnitude of this cell cycle phenotype increases as a function of increasing intracellular Tag concentration. This effect of Tag on the cell cycle is not independent of negative regulation by cellular mechanisms since exponentially growing cell populations producing high and increasing levels of Tag, increase the fraction of cells residing in G1 and decrease the fraction in S and G2+M as a function of cell density. Therefore, the data in this paper show, first, that Tag is a concentration-dependent, positive cell cycle regulator in exponentially proliferating cells and, second, that endogenous cellular mechanisms negatively regulating the cell cycle in response to cell density override the effect of Tag. PMID- 1620546 TI - Quail neuroretina c-Rmil(B-raf) proto-oncogene cDNAs encode two proteins of 93.5 and 95 kDa resulting from alternative splicing. AB - c-Rmil is the cellular allele of the v-Rmil oncogene transduced during in vitro passaging of Rous-associated virus type 1 in chicken embryonic neuroretina (NR) cells. The c-Rmil proto-oncogene is the avian homolog of the mammalian B-raf gene and belongs to the mil/raf oncogene family of serine/threonine protein kinases. The c-Rmil/B-raf gene is preferentially expressed in avian and mammalian neural tissues. Two c-Rmil cDNA species, resulting from an alternative splicing mechanism, were isolated from quail embryonic NR cDNA libraries. They encode two proteins of 767 and 807 amino acids that differ by the presence of an alternative exon, located upstream of the kinase domain. Expression of these cDNAs in COS-1 cells leads to the synthesis of two proteins with apparent molecular weights of 93.5 and 95 kDa, recognized by an Rmil-specific antiserum. Both proteins are phosphorylated in an immune complex kinase assay. A protein of 94 kDa is also immunoprecipitated in avian NR cells and is identical to the 93.5-kDa protein expressed in COS-1 cells, as shown by Staphylococcus aureus V8 protease mapping. The c-Rmil proteins contain the three conserved regions previously identified in mil/raf protein kinases. In addition, they contain amino-terminal sequences that are not present in the other mil/raf proteins identified to date. These additional sequences may define a novel functional domain for c-Rmil/B-raf and could play a role in signal transduction in neural cells. PMID- 1620547 TI - Detection of the PTC/retTPC oncogene in human thyroid cancers. AB - We have investigated the PTC/retTPC oncogene, an activated form of ret proto oncogene with a specific rearrangement, in thyroid malignancies. Southern analysis was used to screen 36 thyroid papillary carcinomas (PC), 22 normal thyroid tissues from glands with PC elsewhere, three follicular carcinomas, eight follicular adenomas and 30 other non-malignant thyroids. Rearrangements were detected in four PCs (11%) using probes derived from the ret proto-oncogene. Genomic breakpoints from a PC and a PC cell line (TPC-1) were cloned and sequenced. The rearrangement points of ret proto-oncogene were found in the intron between the exon for the transmembrane domain and the first exon for the tyrosine kinase domain. Furthermore, the PTC/retTPC chimeric transcripts were detected in two PCs with the rearrangement by reverse transcription polymerase chain reaction. Distant metastases were present in 50% (2/4) of PCs with the rearrangement, but in only two out of 32 PCs without a detectable rearrangement (P = 0.05, Fisher exact test). Our study suggests that the rearrangement of the ret proto-oncogene may be involved in the development of distant metastases in patients with papillary thyroid carcinomas. However, a larger clinical study will be required to verify this observation. PMID- 1620548 TI - JAK2, a third member of the JAK family of protein tyrosine kinases. AB - We have isolated cDNA clones encoding a third, widely expressed, member of the JAK family of protein tyrosine kinases (PTKs). The anticipated amino acid sequence of JAK2 predicts the presence of two kinase-related domains, a feature characteristic of this family of PTKs. The structural similarity of JAK2 to the other members of this family extends towards their N-termini, beyond the two kinase-related domains, and reveals five further domains of substantial amino acid similarity. The C-terminal portion of one of these domains, the JH4 domain, bears an intriguing, albeit tenuous, similarity to the core element of the SH2 domain, whereas the remaining JAK homology domains do not appear to be a feature of other known proteins. PMID- 1620549 TI - Phosphorylation of the p53 tumour-suppressor protein at three N-terminal sites by a novel casein kinase I-like enzyme. AB - Wild-type mouse p53, expressed in Escherichia coli, was phosphorylated by highly purified casein kinase I (CKI) from rabbit muscle. The major site of phosphorylation in the p53 was identified as serine 6, which is known to be phosphorylated in vivo. Serines 4 and 9 were also phosphorylated. To determine whether CKI is likely to be a physiological p53 kinase, SV3T3 cell lysates were fractionated on a Mono Q column and assayed for p53 kinase and casein kinase activities. Four p53 kinase activities were detected, one of which co-purified with CKI activity. This p53 kinase (designated PK270) further co-purified with CKI on sucrose gradients and had a native molecular weight, like CKI, in the range of 35,000-45,000. However, PK270 was separated from the bulk of CKI activity on a phosvitin-Sepharose affinity column, and was therefore likely to be a CKI-related kinase. In support of these conclusions, phosphorylation of p53, by both CKI and PK270, was inhibited by a peptide corresponding to a consensus CKI target sequence, but not by a non-specific peptide. Moreover, phosphopeptide analyses of p53 phosphorylated by CKI or by PK270 gave similar results, indicating that these two kinases phosphorylate the same sites in p53. PMID- 1620550 TI - Correlation between the conformational phenotype of p53 and its subcellular location. AB - In order to obtain insight into the parameters determining the subcellular localization of mutant and wild-type forms of p53, we analysed the subcellular distribution of p53 in four Balb/c mouse-derived cell lines ranging in their cellular phenotypes from normal (3T3), via minimal transformant (T3T3), to maximally transformed (3T3tx, Meth A). Epitope mapping showed the p53 proteins in 3T3 and in T3T3 cells to be in a wild-type conformation, as they reacted with PAb246, whereas p53 in 3T3tx and in Meth A cells were PAb246 negative and thus displayed a mutant conformation. Despite its reactivity with PAb246, p53 in T3T3 cells had an extended half-life and accumulated to abnormally high levels. We show that the conformationally wild-type p53 in 3T3 and T3T3 cells predominantly localized to the cell nucleus, with about half of it being tightly associated with nuclear structures. In contrast, approximately 60% of mutant p53 in 3T3tx and Meth A cells localized to the cytoplasm, the rest residing in the cell nucleus; all the nuclear p53 in these cells appeared to be structurally bound. The cytoplasmic location of mutant p53 in 3T3tx and Meth A cells was not seen by immunofluorescence microscopic analysis, and required cell fractionation for its detection. Both cytoplasmic and nuclear p53 of the mutant phenotype bound to hsc proteins with a similar stoichiometry, suggesting that hsc binding is not directly related to the subcellular distribution of these proteins. We suggest that the conformational phenotype of p53 is a major determinant of its subcellular location. PMID- 1620551 TI - Evidence for synergistic interactions between ras, myc and a mutant form of p53 in cellular transformation and tumor dissemination. AB - Mouse 10T1/2 cells were transfected with combinations of T24 H-ras, human c-myc and the proline 193 mutant form of p53. The three-gene ras/myc/p53 combination was significantly more efficient than single genes or double gene combinations in inducing transformed foci in vitro. An analysis of cell lines isolated after transfections with ras, ras/myc, ras/p53 and ras/myc/p53 indicated that the last combination contained significantly higher levels of ras protein than the other combinations, produced tumors in syngeneic mice with a shorter latency period, and exhibited an increased ability to form lung tumors in an in vivo experimental metastasis assay. Synergistic interactions between ras, myc and mutant p53 genes were observed in focus formation and metastasis assays, suggesting that the action of the three oncogenes in malignant transformation occurs along separate but interactive pathways. These results support a working model of oncogene cooperativity in which alterations in myc and p53 permit elevated expression of ras, which is important in a mechanism affecting both cellular transformation in vitro and tumor dissemination in vivo. PMID- 1620552 TI - Differences in GTPase-activating protein activity between liver tumors and normal liver tissue in mice. AB - The intrinsic GTPase activity of the cellular protein p21ras is strongly increased by two cytosolic proteins, the GTPase-activating protein (GAP) produced by the neurofibromatosis type 1 gene (NF1-GAP) and a GAP of 120 kDa molecular mass (p120-GAP). The GAP-mediated stimulation of p21ras GTPase activity was measured in cytosol obtained from carcinogen-induced liver tumors and normal liver tissues of mice of two strains, namely C3H/He and C57BL/6J. For this purpose, cytosolic extracts were incubated with recombinant human p21ras complexed to [gamma-32P]GTP and the time-dependent decrease in p21ras bound radioactivity was measured. Liver cytosolic extracts mediated an increase in the GTPase activity of wild-type p21ras. There were great differences between tumor and normal tissues in the maximal velocity (Vmax) and in the apparent Michaelis constant (KM) of the p21ras GTPase reaction. Both Vmax and apparent KM were decreased in the liver tumors. Cytosolic extracts isolated from liver tumors that harbored point mutations in codon 61 of the c-H-ras gene did not differ in their activity from extracts obtained from non-mutated liver tumors. Since both GAP proteins are important cellular regulators of the ras signaling pathway and probably also effectors of p21ras, the observed differences in GAP activity may be of relevance for the tumorigenic process in mouse liver. PMID- 1620553 TI - Diet-dependent carcinogenesis of pancreatic islets and liver in transgenic mice expressing oncogenes under the control of the L-type pyruvate kinase gene promoter. AB - The liver-type pyruvate kinase (L-PK) gene is controlled positively by insulin and carbohydrates, negatively by glucagon and fasting. Diet-inducible models of carcinogenesis were obtained using the L-PK gene promoter and regulatory sequences to control the expression of c-myc and SV40 T oncogenes in transgenic mice. L-PK/c-myc and L-PK/Tag animals fed a carbohydrate-rich diet developed hepatocarcinomas. In addition, L-PK/Tag animals developed diet-dependent, aggressive endocrine pancreatic tumors, preceded by islet hyperplasia involving the different analysed cell populations (alpha, beta and delta). Expression of the L-PK gene was demonstrated in pancreatic tumors, in rat isolated islets and in rat insulinoma-derived cells (RIN line), revealing a new tissue specificity of the L-PK gene. Our results suggest that this gene may be expressed in islet progenitor cells from which the different mature endocrine cells derive. PMID- 1620554 TI - Phylogeny of the p68c-ets-1 amino-terminal transactivating domain reveals some highly conserved structural features. AB - The chicken c-ets-1 locus gives rise to two distinct transcription factors differing only in their structurally and functionally unrelated N-termini. One of these transcription factors, p54c-ets-1, contains a specific, short (27 amino acids), hydrophilic N-terminus encoded by a single exon, I54, that is widely conserved among vertebrates. The other one, p68c-ets-1, the cellular counterpart of the viral ets oncogene product, differs in the replacement of the I54 by two exons, termed alpha and beta, encoding a larger (71 amino acids), hydrophobic N terminus which, in contrast to I54, exhibits properties of a transactivating domain. To date the alpha and beta exons have only been found in chicken. Here, we demonstrate the existence of the alpha and beta exons in other avian species (quail and duck) and the existence of the alpha exon in reptiles (turtle). However, none of them could be detected in mammals. Our results strongly suggest that, in contrast to the phylogenetically well-conserved I54 exon, the alpha exon is restricted to reptilian species (birds and 'true' reptiles), whereas the beta exon is detectable so far only in birds. Comparison of their amino acid sequences reveals that the alpha exon and to a much greater extent the beta exon have diverged faster than the I54 exon. In addition, we show that the N- and C terminal thirds of the alpha exon and the highly hydrophobic nature of the alpha beta-encoded sequence are heavily conserved features and thus likely to be required for function as a transactivating domain in p68c-ets-1 and possibly in the viral P135gag-myb-ets transforming protein. PMID- 1620555 TI - Detection of phosphorylated retTPC oncogene product in cytoplasm. AB - The product of the retTPC oncogene, an activated form of the ret proto-oncogene found in human papillary thyroid carcinomas, was identified as a 57-kDa protein (p57retTPC) by Western blotting with a polyclonal antibody raised by an oligopeptide corresponding to the carboxy-terminal region of the ret proto oncogene product. Subcellular fractionation experiments using NIH3T3 cell transformants induced by the retTPC cDNA showed that p57retTPC was localized in a soluble cytoplasmic fraction, whereas the ret proto-oncogene products expressed in a neuroblastoma cell line were present in a membrane fraction. Immunostaining also demonstrated that p57retTPC is localized in the cytoplasm. Immunoprecipitation with anti-phosphotyrosine antibody followed by Western blotting revealed that p57retTPC is constitutively phosphorylated, whereas the ret proto-oncogene products are not. These findings suggest that p57retTPC has an aberrant tyrosine kinase activity resulting in autophosphorylation associated with change in its location. PMID- 1620556 TI - Annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc. Washington, D.C., September 13-17, 1992. Instructional Course program. PMID- 1620557 TI - A pediatrician's view. A lead balloon. PMID- 1620558 TI - Advances in neonatal neurology. PMID- 1620559 TI - Clinical evaluation of the floppy infant. AB - The list of possible diagnoses for floppiness in infancy is extensive, with potentially hundreds of rare diseases. Nonetheless, most floppy infants have distinctive features in the history, the family history, or the physical examination that quickly narrow the list to central or motor unit disorders, and often to specific diagnoses within these broad groups. Accurate diagnosis is important, as outcomes are similarly protean, genetic implications are frequent, and in some cases specific treatments are possible. PMID- 1620560 TI - What have we learned from febrile seizures? AB - What have we learned from febrile seizures? We have learned that there is a natural history to different seizure types, what some have taken to calling "seizure syndromes." We have learned that understanding these "natural histories" may be helpful in making decisions about treatment. We have learned that seizures themselves, while unpleasant, may not be harmful and don't always have to be treated. We have learned that sometimes the treatment is worse than the disease and that the side effects of medication may have more consequences than the occurrence of another seizure. We have learned that the determination of the "risks" and consequences of the seizures should be made by the patient or the family, and that they may assess the risks and benefits quite differently than the physician. Similarly, the benefits and consequences of anticonvulsant medication may be assessed quite differently by different people. We have learned that all seizures do not need to be treated, and we have learned that those that are treated should be treated for the shortest time possible. I believe that these are important lessons that should affect our management of afebrile seizures as well. PMID- 1620561 TI - Chronic recurrent headaches in children. AB - Chronic recurrent headaches in children can be classified into distinct categories based on a careful history and physical examination. Migraine and muscle contraction headaches are common in the pediatric population. Laboratory studies should be limited to those individuals who have other signs or symptoms accompanying headaches that raise concern. Reassurance about the underlying pathophysiology of vascular or muscle contraction headaches, their benign nature, and favorable prognosis may not only relieve associated anxiety that may produce or prolong headache, but also may relieve the headache itself. Symptomatic mild analgesics and behavioral medicine therapy are often sufficient, although occasionally prophylactic pharmacotherapy is required. The long-term prognosis for children with chronic recurrent headaches is generally favorable. PMID- 1620562 TI - Ischemic stroke syndromes in childhood. AB - Cerebral ischemic injury is uncommon in children, but the effects are long lasting with significant implications for the child's development. The precipitating event in ischemic infarct is generally occlusion of the cerebral vessels. This occlusion may the result of direct injury of the cerebral vasculature, thrombus formation, or emboli from more distant sources. A wide variety of conditions are known to predispose to cerebral infarcts in children. However, even in recent studies, the underlying condition is unknown in as many as half the children who suffer an ischemic stroke. To care for these children effectively, it is imperative that extensive evaluations be performed to determine the cause of the cerebral infarct. Furthermore, increasing attention will need to be directed toward the metabolic events of cerebral ischemia. A better understanding of these mechanisms may provide clues to some of the causes of ischemic injury and should lead to more effective treatments. PMID- 1620563 TI - Neurologic concepts of lead poisoning in children. PMID- 1620564 TI - Hysteresis, cooperativity, and depth averaging in dynamic random-dot stereograms. AB - Experiments were performed to assess the response of the human visual system to dynamic random-dot patterns composed of disparity mixtures. In Experiment 1, the perceived depth and relative stability of two patterns were compared; one pattern depicted two transparent layers of dots, and the other depicted a volume of dots. Two effects were found: (1) the volume pattern exhibited a large degree of disparity averaging; and (2) asymmetries were observed in the relative stability of these two patterns. Experiment 2 was designed to determine whether these findings could be attributed to spatially localized processes occurring at the location of disparity discontinuities. This was accomplished by introducing unpaired noise points localized either along the disparity discontinuities or in the center of the layered and volume patterns. The amount of depth averaging and the direction of the asymmetry did not appear to depend on processes localized along the disparity discontinuities. Results of these experiments, taken in conjunction with those of previous studies, suggest that hysteresis is independent of cooperative persistence mechanisms. PMID- 1620565 TI - A comparison of generalization functions and frame of reference effects in different training paradigms. AB - Six experiments were carried out to compare go/no-go and choice paradigms for studying the effects of intradimensional discrimination training on subsequent measures of stimulus generalization in human subjects. Specifically, the purpose was to compare the two paradigms as means of investigating generalization gradient forms and frame of reference effects. In Experiment 1, the stimulus dimension was visual intensity (brightness); in Experiment 2, it was line orientation (line-angle stimuli). After learning to respond (or to respond "right") to stimulus value (SV) 4 and not to respond (or to respond "left") to SV2 (in Experiment 1) or SV1 (in Experiment 2), the subjects were tested for generalization (recognition) with an asymmetrical set of values ranging from SV1 to SV11. Go/no-go training produced peaked gradients, whereas choice training produced sigmoid gradients. The asymmetrical testing resulted in a gradual shift of the peak of responding (go/no-go group) or in the point of subjective indifference (PSI; choice group) toward the central value of the test series; thus, both paradigms revealed a frame of reference effect. The results were comparable for the quantitative (intensity) and the qualitative (line-angle) stimulus dimensions. Experiment 3 compared the go/no-go procedure with a yes/no procedure in which subjects responded "right" to SV4 and "left" to all other intensities and found no differences between these procedures. Thus the difference in gradient forms in go/no as opposed to (traditional) choice paradigms depends on whether one or two target stimuli are used in training. In Experiment 4, in which visual intensity was used, the shift in the PSI following choice training varied positively with the range of asymmetrical test stimuli employed. In Experiment 5, also with visual intensity, the magnitude of the peak shift following go/no-go training varied as a function of overrepresenting a high or a low stimulus value during generalization testing. Experiment 6, with line angles, showed that the PSI following choice training varies in a similar way. The frame of reference effects obtained in these experiments are consistent with an adaptation-level model. PMID- 1620566 TI - Size-distance invariance: kinetic invariance is different from static invariance. AB - The static form of the size-distance invariance hypothesis asserts that a given proximal stimulus size (visual angle) determines a unique and constant ratio of perceived object size to perceived object distance. A proposed kinetic invariance hypothesis asserts that a changing proximal stimulus size (an expanding or contracting solid visual angle) produces a constant perceived size and a changing perceived distance such that the instantaneous ratio of perceived size to perceived distance is determined by the instantaneous value of visual angle. The kinetic invariance hypothesis requires a new concept, an operating constraint, to mediate between the proximal expansion or contraction pattern and the perception of rigid object motion in depth. As a consequence of the operating constraint, expansion and contraction patterns are automatically represented in consciousness as rigid objects. In certain static situations, the operation of this constraint produces the anomalous perceived-size-perceived-distance relations called the size-distance paradox. PMID- 1620567 TI - The effect of orientation on tactual braille recognition: optimal touching positions. AB - Subjects in five experiments matched tangible braille against a visible matching code. In Experiment 1, braille recognition suffered when entire lines of braille characters were tilted in varying amounts from the upright. Experiment 2 showed that tilt lowered performance for tangible, large embossed letters, as well as for braille. However, recognition was better for print letters than it was for braille. In Experiment 3, subjects attempted to match the upright array against embossed braille that was left/right reversed, inverted up/down, or rotated +180 degrees. Performance was close to that for normal braille in the left/right reversal condition, and very low for the +180 degrees rotation group. These results on braille tilt in the "picture plane" may reflect difficulty in manipulating the tangible "image." Braille recognition performance was not lowered when the visible matching array was tilted -45 degrees or -90 degrees from the upright but the tangible stimuli were upright. In Experiment 4, recognition of left/right reversed braille that was physically horizontal (on the bottom of a shelf) was compared with that of braille left/right reversed due to its location on the back of a panel, in the vertical plane. Braille recognition accuracy was higher with braille located vertically. An additional experiment showed the beneficial effect of locating braille in the vertical, frontoparallel plane, obtained with +90 degree rotated braille. It is proposed that optimal tactual performance with tangible arrays might depend on touching position, and on the physical position of stimuli in space. Just as there are good and poor viewing positions, there may be optimal touching positions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620568 TI - Active regulation of altitude as a function of optical texture. AB - Two empirical studies are reported that examine active regulation of altitude as a function of the type of ground texture. Three ground textures were examined: lines perpendicular to the direction of motion, lines parallel to the direction of motion, and the combination (i.e., square or checkerboard texture). Although subjects only controlled altitude, disturbances were introduced on three axes: vertical, lateral, and fore-aft. The results show a clear advantage for texture parallel to the direction of motion. However, in considering these results in the context of previous research on altitude control, the argument is made that there is no compelling evidence that suggests either parallel (splay) or perpendicular (density) texture is privileged with regard to altitude control. Rather, the most effective display for altitude control will be the one that best isolates the optical activity associated with changing altitude from the optical activity arising from other sources of disturbance (such as forward locomotion). Such a display will make it easier for the observer to distinguish and respond specifically to the disturbances of altitude. PMID- 1620569 TI - Visually controlled matching of pattern movement. AB - Subjects were asked to match the speeds of two moving random-dot patterns seen through circular apertures. The speed of one pattern that moved horizontally toward the right of a computer screen changed continuously. The speed of this pattern represented the target. It was to be matched with the speed of the second pattern, which moved in the opposite direction. The subject controlled the speed of the second pattern by means of an isometric joystick. The distance between the apertures on the screen as well as the subject's distance from the screen served as experimental parameters. In this way, the effects of both spatial and temporal transients of pattern speed on human tracking performance were studied. To avoid anticipation by the subject, the amplitude and the frequency of the target pattern speed changed pseudorandomly. The accuracy with which the subject performed the matching task was influenced by the mean pattern speed and the parameters of the visual field. Within lower velocity ranges, the subject's sensitivity to the instantaneous speed differences varied according to Weber's law. The cross-correlation of the velocity time courses decreased when the mean speed of the target pattern was increased. Two stimulus parameters had a strong influence on the modulation of the correlation value: (1) the angular size of the stimulus on the retina and (2) the retinal eccentricity of the stimulus. PMID- 1620570 TI - Haptic probing: perceiving the length of a probe and the distance of a surface probed. AB - Knowing about the properties of objects by wielding them and knowing about the distances of surfaces by striking them with objects as probes are examples of dynamic or effortful touch. Six experiments focused on the invariant mechanical parameters that couple the time-varying states (displacements, velocities) of hand-held rods to the time-varying torques and forces imposed upon them by wielding and probing. There were three major conclusions. First, when a probe is wielded without contact, perceived probe length is a function of the probe's rotational inertia; however, with contact, perceived probe length is affected by the rotational inertia and the distance of the point of contact from the probe's center of percussion. Second, when a surface is struck with a probe, perceived surface distance is affected by the probe's rotational inertia and the angle of inclination of the probe at contact. Third, under seemingly identical conditions of probing, either probe length or surface distance can be perceived selectively without confusion. Results were discussed in terms of haptic information, haptic attention, and the dynamics of probing. PMID- 1620571 TI - Perceptual selectivity for color and form. AB - Three visual-search experiments tested whether the preattentive parallel stage can selectively guide the attentive stage to a particular known-to-be-relevant target feature. Subjects searched multielement displays for a salient green circle that had a unique form when surrounded by green nontarget squares or had a unique color when surrounded by red nontarget circles. In the distractor conditions, a salient item in the other dimension was present as well. As an extension of earlier findings (Theeuwes, 1991), the results showed that complete top-down selectivity toward a particular feature was not possible, not even after extended and consistent practice. The results reveal that selectivity depends on the relative discriminability of the stimulus dimensions: the presence of an irrelevant item with a unique color interferes with parallel search for a unique form, and vice versa. PMID- 1620572 TI - Expectancy and stimulus frequency: a comparative analysis in rats and humans. AB - We examined whether expectancy, one of several factors influencing attention, is similarly affected in rats and humans by manipulation of relative stimulus frequency. A two-choice reaction time (RT) task was developed for rats, and an analogous task was used for humans. Errors, RTs, discriminability, and response bias were measured. Both rats and humans shifted their response bias to the more frequent stimulus, with no change in overall discriminability. As stimulus probability or stimulus repetition increased, RTs and errors decreased. These results illustrate the similarity of expectancy in rats and humans. This two choice RT task for rats can be used in future studies to examine the neuronal mechanisms of expectancy and attention. PMID- 1620573 TI - High impedance mechanical ventilator for small animals: use of programmable controller. AB - We built a simple high impedance ventilator, which generates a pattern of flow largely independent of respiratory mechanics, to mechanically ventilate anaesthetized small animals. The system includes a source of compressed gas with an electronic valve and a flow controller on the inspiratory side and a second valve on the expiratory side. The two valves are driven by a programmable controller. To assess the performance of this ventilator we measured the delivered tidal volume while the ventilator was connected to an external, gradually varying resistance. This resistance was progressively increased to simulate bronchoconstriction of the respiratory system. Comparison with a volume controlled ventilator was made. The use of a programmable controller also allows control of different patterns of mechanical ventilation, such as end-inspiratory pause or the static pressure-volume relationship, which can be used to perform lung function tests. The system is a simple, versatile device allowing both reliable mechanical ventilation and lung function assessment in small rodents and is suitable for routine use in laboratories. PMID- 1620574 TI - Role of endothelium in the response of the vein wall to magnesium withdrawal. AB - Complete absence of magnesium has a two-fold effect on the arterial tone: direct smooth muscle contraction and relaxation via endothelium-derived relaxing factor (EDRF) release. In the present study performed on a systemic vein we investigated (1) which of these effects dominates following reduction of magnesium concentration from 1.2 mM to 0.8 and 0.4 mM and (2) whether the vessel segments asymmetrically respond when the magnesium concentration is reduced on either the intra- or extraluminal side. The effects of reducing magnesium concentration on both the isometric tension of isolated ring preparations and the diameter of isolated, perfused and superfused feline femoral veins were investigated. In noradrenaline-precontracted rings, rapid decreases in the extracellular magnesium concentration from 1.2 mM to 0.8 and 0.4 mM caused relaxation, whereas total omission of magnesium returned the tone to the level of the initial tone induced by noradrenaline. Both in the presence of haemoglobin (5 x 10(-6) M), and in vessels without endothelium, lowering the magnesium concentration caused a dose dependent elevation of the noradrenaline-induced tone. In perfused and superfused noradrenaline-contracted vein segments, each reduction of extraluminal magnesium concentration caused contraction of the vessels, regardless of whether the endothelium was intact or not. A decrease in intraluminal magnesium concentration did not alter the diameter of the vessel when the endothelium was intact, but caused contraction when the endothelium was disrupted. The results of the present study demonstrate that both the reduction of magnesium concentration or its complete absence cause an EDRF-mediated relaxation and a directly mediated smooth muscle contraction in the femoral vein of the cat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620575 TI - Tubular sodium handling and tubuloglomerular feedback in compensatory renal hypertrophy. AB - Tubular sodium handling and tubuloglomerular feedback (TGF) activity were assessed in established compensatory renal hypertrophy in Sprague Dawley rats. Hyperfiltration at the level of the single nephron was confirmed 4-6 weeks following a reduction in renal mass. TGF activity, determined as the difference between late proximal and early distal measurements of single-nephron glomerular filtration rate (SNGFR), was significantly increased in compensatory renal hypertrophy, being 7.8 +/- 1.0 vs 23.3 +/- 1.9 vs 25.5 +/- 2.6 nl/min (P for analysis of variance less than 0.05) following sham operation, unilateral nephrectomy, and 1 1/3 nephrectomy, respectively. Enhanced net tubular Na transport was also observed, with total Na reabsorption up to the late proximal site being 1.8 +/- 0.2 vs 2.7 +/- 0.1 vs 3.1 +/- 0.3 nmol/min (P less than 0.05), and to the early distal site being 3.4 +/- 0.5 vs 5.8 +/- 0.6 vs 7.9 +/- 0.8 nmol/min (P less than 0.05) in the three animal groups respectively. Comparison of proximal tubular length demonstrated a 71.9 +/- 8.1% increase in uninephrectomised vs sham-operated animals. This increase was proportionately greater than the increase in proximal Na reabsorption (50.0 +/- 4.0%) observed in the corresponding animal groups. Concurrent electron microprobe experiments in uninephrectomised and sham-operated animals demonstrated that the proximal tubular intracellular Na concentration was significantly lower following uninephrectomy (16.8 +/- 0.6 vs 18.9 +/- 0.5 mmol/kg wet weight, P less than 0.01), in association with evidence of reduced basolateral Na/K-ATPase activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620576 TI - Immunological rejection of heart transplant: how lytic granules from cytotoxic T lymphocytes damage guinea pig ventricular myocytes. AB - We investigated the mechanism by which lytic granules extracted from cytotoxic T lymphocytes (CTL) damage guinea pig ventricular myocytes in order to determine whether their actions can be related to the overall immunological rejection of the transplanted heart. Granule-induced myocyte morphological changes and final destruction were preceded by shortening of action potential duration (APD) and reductions of the resting potential and the action potential amplitude. APD shortening was probably caused by a granule-induced increase in outward current (most likely non-specific). Ryanodine, which blocks Ca2+ release from the sarcoplasmic reticulum, did not interfere with the morphological and electrophysiological effects of lytic granules. Fura-2 imaging indicated that [Ca2+]i initially increased about 2-fold from 90.0 +/- 11.5 nM, while cell length decreased less than 5% from a mean value of 99.0 +/- 9.0 microns. A further increase in [Ca2+]i (greater than 10 fold) was associated with progressive contracture and destruction, suggesting that the structural damage inflicted by lytic granules is caused by [Ca2+]i overload. The results indicate that the cytocidal action of CTL-derived lytic granules may be involved in immunologically induced damage, even to the extent of rejection of the transplanted heart. PMID- 1620577 TI - Role of external Ca2+ and K+ in gating of cardiac delayed rectifier K+ currents. AB - We sought to determine whether extracellular Ca2+ (Ca2+e) and K+ (K+e) play essential roles in the normal functioning of cardiac K+ channels. Reports by others have shown that removal of Ca2+e and K+e alters the gating properties of neural delayed rectifier (IK) and A-type K+ currents, resulting in a loss of normal cation selectivity and voltage-dependent gating. We found that removal of Ca2+e and K+e from the solution bathing guinea pig ventricular myocytes often induced a leak conductance, but did not affect the ionic selectivity or time dependent activation and deactivation properties of IK. The effect of [K+]e on the magnitude of the two components of cardiac IK was also examined. IK in guinea pig myocytes is comprised of two distinct types of currents: IKr (rapidly activating, rectifying) and IKs (slowly activating). The differential effect of Ca2+e on the two components of IK (previously shown to shift the voltage dependence of activation of the two currents in opposite directions) was exploited to determine the role of K+e on the magnitude of IKs and IKr. Lowering [K+]e from 4 to 0 mM increased IKs, as expected from the change in driving force for K+, but decreased IKr. The differential effect of [K+]e on the two components of cardiac IK may explain the reported discrepancies regarding modulation of cardiac IK conductance by this cation. PMID- 1620578 TI - Role of nitric oxide in local blood flow control in the anaesthetized dog. AB - Intravenous infusion of NG-nitro-L-arginine methyl ester (L-NAME), a potent inhibitor of nitric oxide (NO) formation from L-arginine, provokes marked rises in arterial blood pressure by increasing peripheral resistance. In order to further evaluate the contribution of basal NO-formation to control of organ blood flow, regional blood flow distribution within the myocardium, kidney and brain areas was assessed using the tracer-microsphere technique in anaesthetized dogs. After L-NAME (20 mg kg-1 i.v.) kidney perfusion was homogeneously reduced by 55% in the entire cortex and the outer medulla. Within the left ventricular myocardium regional blood flow significantly decreased only in subepicardial layers (-12%), whereas within the entire right ventricle regional blood flow was reduced by 19-24%. A close inverse relationship was found between all changes in regional myocardial blood flows observed after L-NAME and the respective control values. No significant changes in regional blood flow in different areas of the brain were detectable after L-NAME. It is concluded that the contribution of basal NO formation varies greatly between different organs and exhibits significant regional differences within the heart. It is possible that local metabolic mechanisms may compensate functionally for the inhibition of NO synthesis. PMID- 1620579 TI - Mechanism of intracellular calcium oscillations in fibroblasts expressing the ras oncogene. AB - In NIH fibroblasts expressing the ras oncogene bradykinin leads to sustained, calcium-dependent oscillations of cell membrane potential by oscillating activity of calcium sensitive potassium channels. The present study has been performed to further analyse the underlying mechanisms. In cells expressing the oncogene, but not in NIH fibroblasts not expressing the oncogene, bradykinin elicits calcium oscillations, which are detected by fura-2 fluorescence and amplified by a decrease of extracellular sodium activity. These calcium oscillations are dependent on the presence of extracellular calcium and are inhibited by lanthanum ions. It is concluded that in cells expressing the ras oncogene, bradykinin activates lanthanum sensitive calcium entry from the extracellular space. Ras oncogene expression leads to enhanced bradykinin-induced formation of both, 1, 4, 5 inositoltrisphosphate and 1, 3, 4, 5 inositoltetrakisphosphate, an effect probably accounting for the oscillations of intracellular calcium activity. PMID- 1620581 TI - Development, refinement, and future directions of the model. PMID- 1620580 TI - Activation of different pathways for calcium elevation by bradykinin and ATP in rat pheochromocytoma (PC 12) cells. AB - We have studied the pathways by which extracellular bradykinin and adenosine 5' triphosphate (ATP) elicit changes in intracellular free calcium ([Ca2+]i) in nerve-growth-factor(NGF)- treated rat pheochromocytoma (PC 12) cells. Both substances caused a significant rise in [Ca2+]i as assessed by fura-2 based microfluorimetry. The bradykinin-induced response consisted of an initial Ca2+ mobilization from an internal pool followed by a sustained increase in [Ca2+]i, which was due to activation of a small inward current. The initial response always started at a localized site opposite to the cell nucleus. The inward current was partially carried by Ca2+ and began with a time lag of about 4 s after the start of the initial transient signal. Stepwise hyperpolarization of the plasma membrane, after activation of the inward current by bradykinin, caused a simultaneous increase in current amplitude and in [Ca2+]i, due to an increase in the driving force for Ca2+ influx. With ATP as an agonist the onset of inward current coincided with an increase in [Ca2+]i. Inward current and [Ca2+]i were enhanced during hyperpolarizing steps indicating a substantial Ca2+ influx through ATP-activated channels. No release of Ca2+ from internal stores, but a large Na+ inward current, was observed in Ca(2+)-free external solution after addition of ATP. While the bradykinin-induced responses were much more pronounced in cell bodies than in growth cones, the ATP effects were somewhat variable in cell bodies and more homogeneous in growth cones. PMID- 1620582 TI - Models for the next century. AB - The Loomis/Wood Model offers potential to influence what hangs in the balance for the future. It is a model that encompasses conceptual and ideological diversity. It is a model that encourages the use of empirical data applied within a framework of nursing's conceptual and ethical tradition. It is a model that can incorporate rapidly changing demands for more and sometimes different information. It does not prescribe; rather, it encourages contextual and situationally relevant choice on the part of the user. In my view, these are the types of features that will be critical for the next century. PMID- 1620583 TI - Application and utilization of the Loomis/Wood Model as the conceptual framework for curriculum design. PMID- 1620584 TI - Application and utilization of the Loomis/Wood Model as the conceptual framework for the conduct of nursing research. PMID- 1620585 TI - Application of the Loomis/Wood Model as a conceptual framework in nursing practice. PMID- 1620586 TI - Observations on guided tissue regeneration. PMID- 1620587 TI - Self-destruction and tolerance in resistance of mammalian cells to alkylation damage. PMID- 1620588 TI - Differential binding of human nuclear proteins to Alu subfamilies. AB - Several diagnostic differences that distinguish human Alu subfamilies are clustered just downstream from the B box of the RNA polymerase III promoter; we tentatively refer to this diagnostic region as the DB box. Assuming that this region might determine the relative transcriptional activity of Alu subfamilies, we examined the interaction of nuclear proteins with DB box sequences representing different Alu subfamilies. Gel mobility shift assays suggest the existence of two factors which discriminate among the DB boxes of different Alu subfamilies: 1) An abundant, ca. 50 kd, protein binds more stably to a young 'PV' Alu subfamily (PVS) than to the older major subfamily (MS). 2) Methylation of CpG dinucleotides stimulates the binding of a less abundant, ca. 70 kd, protein to the DB boxes of younger Alu subfamilies. PMID- 1620589 TI - Alternative 3' processing of Xenopus alpha-tubulin mRNAs; efficient use of a CAUAAA polyadenylation signal. AB - The Xenopus laevis alpha-tubulin gene X alpha T14 produces two mRNAs of 1.7 and 2.15 kb and we have shown that this is due to the use, at approximately equal frequency, of alternative 3' processing sites. Unusually, the hexanucleotide polyadenylation signal responsible for use of the downstream site, pA2, is CAUAAA in contrast to the consensus AAUAAA used at the upstream site, pA1. Since such a variant hexanucleotide would normally be expected to reduce drastically the efficiency of 3' processing, we have examined the 3' flanking sequences involved in pA2 usage in injected oocytes. In deletion mutants with 40 bp or 440 bp of 3' flanking DNA use of pA2 was almost totally abolished whereas when 770 bp of the natural flank was present pA2 was used normally. This polyadenylation signal therefore requires an unexpectedly large amount of flanking DNA and we have identified in the required region a member of a novel family of 450 bp interspersed repeats that we have termed Pir elements. We speculate that because of the variant hexanucleotide efficient use of pA2 has to be potentiated by the Pir element, perhaps through an effect on transcriptional pausing or termination. PMID- 1620590 TI - Expression of the arylsulfatase gene from the beta 2-tubulin promoter in Chlamydomonas reinhardtii. AB - Arylsulfatase, produced by Chlamydomonas reinhardtii during sulfur-limited growth, is secreted into the periplasmic space and is readily assayed using a chromogenic substrate. To assess the usefulness of the gene encoding arylsulfatase (ars) as a reporter gene in C. reinhardtii, we have fused the promoter region of the beta 2-tubulin gene (tubB2) to the coding region of an ars genomic clone to form a tubB2/ars chimeric sequence. This construct was introduced into C. reinhardtii, strain CC425 (cw-15, arg-2), via cotransformation with the argininosuccinate lyase gene (which complements the arg-2 lesion) (1). Transformants expressing arylsulfatase (Ars) in sulfur-sufficient medium were isolated and subsequently shown to contain the tubB2/ars gene. RNA analysis determined that tubB2/ars transcripts accumulated in these cells. Abundance of the chimeric transcript increased immediately following deflagellation in a manner similar to that of the endogenous tubB2 transcript. Thus, chimeric genes incorporating ars coding sequences and heterologous promoters can be used to examine regulated gene expression in C. reinhardtii. PMID- 1620591 TI - Targeted integration of neomycin into yeast artificial chromosomes (YACs) for transfection into mammalian cells. AB - Vectors have been constructed for the introduction of the neomycin resistance gene (neo) into the left arm, right arm or human insert DNA of yeast artificial chromosomes (YACs) by homologous recombination. These vectors contain a yeast selectable marker Lys-2, i.e. the alpha-aminoadipidate reductase gene, and a mammalian selection marker, neo, which confers G418 resistance. The vectors can be used to modify YACs in the most commonly used yeast strain for YAC library construction, AB1380. Specific targeting can be carried out by transfection of restriction endonuclease treated linear plasmids, with highly specific recombinogenic ends, into the YAC containing yeast cells. Analysis of targeted YACs confirmed that all three vectors can target correctly in yeast. Introduction of one of the targeted YACs into V79 (Chinese hamster fibroblast) cells showed complete and intact transfer of the YAC. PMID- 1620592 TI - The two main rDNA size classes of Ascaris lumbricoides: comparison of transcription termination and spacer organization. AB - Structural and functional analyses were carried out to compare transcription termination and intergenic spacer organization between the two heterogeneous ribosomal DNA size classes of Ascaris lumbricoides. By performing mung bean nuclease mapping in vivo, we localized the 3' end of the mature 26S rRNA to the same position in both forms. This site coincides with the in vivo and in vitro transcription termination site of the 40S-precursor rRNA from both rDNA size classes. We demonstrate that the 3' boundary of sequences necessary for faithful transcription termination extends 35 bp beyond the end of the 26S rRNA gene and that these sequences are perfectly conserved within the two size classes. The intergenic spacers of both rDNA size classes have been completely sequenced; they are 2410 bp and 1937 bp long and show a sequence homology of 92.8%. There is no evidence for the presence of reiterated termination sites or promoters within the relatively short intergenic spacers of the two rRNA gene classes. PMID- 1620593 TI - Multiple mRNA species generated by alternate polyadenylation from the rat manganese superoxide dismutase gene. AB - The mitochondrial enzyme, manganese superoxide dismutase (MnSOD) is an integral component of the cell's defense against superoxide-mediated cellular damage. We have isolated and characterized four cDNA clones and the structural gene for rat MnSOD. Northern analyses using MnSOD cDNA probes detected at least five mRNAs in all tissues and cell types examined. Southern and Northern analysis using a 3' non-coding sequence probe, common to all the cDNAs, showed hybridization only to genomic restriction fragments that correspond to our genomic clone and the five MnSOD mRNAs. These data demonstrate that all of the rat MnSOD transcripts are derived from a single functional gene. Primer extension data indicate that transcription initiation is clustered within a few bases. Northern analysis using intron probes demonstrates that all five transcripts are fully processed. Northern analysis using cDNA and genomic probes from sequences progressively 3' to the end of the coding sequence indicates that size heterogeneity in the MnSOD transcripts results from variations in the length of the 3' non-coding sequence. From this data and the location of potential polyadenylation signals near the expected sites of transcript termination, we conclude that the existence of multiple MnSOD mRNA species originate as the result of alternate polyadenylation. PMID- 1620594 TI - Activity of chimeric RNAs of U6 snRNA and (-)sTRSV in the cleavage of a substrate RNA. AB - U6 small nuclear RNA is one of the spliceosomal RNAs essential for pre-mRNA splicing. Discovery of mRNA-type introns in the highly conserved region of the U6 snRNA genes led to the hypothesis that U6 snRNA functions as a catalytic element during pre-mRNA splicing. The highly conserved region of U6 snRNA has a structural similarity with the catalytic domain of the negative strand of the satellite RNA of tobacco ring spot virus [(-)sTRSV], suggesting that the highly conserved region of U6 snRNA forms the catalytic center. We examined whether synthetic RNAs consisting of the sequence of the highly conserved region of U6 snRNA or various chimeric RNAs between the U6 region and the catalytic RNA of ( )sTRSV could cleave a substrate RNA that can partially base-pair with them and have a GU sequence. Chimeric RNAs with 70 to 83% sequence identity with the conserved region of S. pombe U6 snRNA cleaved the substrate RNA at the 5' side of the GU sequence, which is shared by the 5' end of an intron in a pre-mRNA. We found that the highly conserved region of U6 snRNA and the catalytic domain of ( )sTRSV are strikingly similar in structure to the catalytic core region of the group I self-splicing intron in cyanobacteria. These results suggest that U6 snRNA, (-)sTRSV and the group I self-splicing intron originated from a common ancestral RNA, and support the hypothesis that U6 snRNA catalyzes pre-mRNA splicing reaction. PMID- 1620595 TI - Post-transcriptional regulation of transferrin receptor mRNA by IFN gamma. AB - IFN gamma inhibits the rise in transferrin receptor mRNA level which is normally observed when stationary WISH cells are stimulated to proliferate. This effect is not attributable to a change in the transcription rate of the transferrin receptor gene or in the cytoplasmic stability of the mRNA. The IFN gamma-induced reduction of the transferrin receptor mRNA content is already present at the nuclear level to an extent comparable to that observed in whole cells. Thus, IFN gamma does not impair the passage of this mRNA from the nuclear to the cytoplasmic compartment but probably interferes with a nuclear post transcriptional event during the processing of the immature transferrin receptor mRNA. Two different levels of regulation of transferrin receptor mRNA have been previously reported. Iron modulates the cytoplasmic stability of this mRNA through the binding of a specific cytoplasmic factor, whereas cell growth variation influences the transcription of this gene. Our results suggest the existence of another mechanism of regulation for transferrin receptor gene expression not so far considered. Furthermore, the distinction between the mechanism of regulation exerted by IFN gamma and that exerted by cell proliferation on transferrin receptor gene expression suggests that, in WISH cells, the IFN-induced transferrin receptor decay is not a consequence of cell growth arrest but rather one of the causes of the antiproliferative effect of IFN through iron deprivation. PMID- 1620596 TI - Nonenymatic ligation of double-helical DNA by alternate-strand triple helix formation. AB - Nonenzymatic ligation of double-stranded DNA has been performed using an alternate-strand binding oligodeoxyribonucleotide template to juxtapose the duplex termini in a triple helical complex. The template associates with the duplex termini by Hoogsteen hydrogen bonding to alternate strands on opposite sides of the ligation site. Intermolecular and intramolecular ligation of linearized plasmid DNA are observed in the reaction, which depends on the template oligodeoxyribonucleotide and a condensing agent, N-cyanoimidazole. Intramolecular ligation products include those in which both strands are covalently closed in a circle. Ligation of the two strands is sequential and occurs at comparable rates for the first and second strands ligating. The covalent linkages formed in the reaction can be cleaved by the restriction endonuclease Stu I, supporting their identification as phosphodiesters. PMID- 1620597 TI - Hoogsteen G-G base pairing is dispensable for telomere healing in yeast. AB - The G-rich strands of most eukaryotic telomeres are capable of forming highly folded structures in vitro, mediated, in part, through Hoogsteen G-G base pairing. The ability of most telomeres to form these structures has led to the suggestion that they play an important role in telomere addition. I have investigated this possibility in the yeast Saccharomyces cerevisiae through the use of an in vivo assay that measures healing via poly(G1-3T) addition onto plasmid substrates containing synthetic telomeres. Synthetic telomere healing is a highly size- and sequence-specific process that allows the discrimination of telomeres of differing efficiency. Plasmids containing synthetic telomeres with differing abilities to form secondary structures were tested in this assay for healing in vivo. The results of this study demonstrate that telomeres incapable of forming Hoogsteen base pairs nonetheless serve as efficient substrates for poly(G1-3T) addition, indicating that intramolecular Hoogsteen G-G base pairing is not essential for this process. PMID- 1620598 TI - Different effects of mioC transcription on initiation of chromosomal and minichromosomal replication in Escherichia coli. AB - The mioC gene, which neighbors the chromosomal origin of replication (oriC) in Escherichia coli, has in a number of studies been implicated in the control of oriC initiation on minichromosomes. The present work reports on the construction of cells carrying different mioC mutations on the chromosome itself. Flow cytometry was employed to study the DNA replication control and growth pattern of the resulting mioC mutants. All parameters measured (growth rate, cell size, DNA/cell, number of origins per cell, timing of initiation) were the same for the wild type and all the mioC mutant cells under steady state growth and after different shifts in growth medium and after induction of the stringent response. It may be concluded that the dramatic effects of mioC mutations reported for minichromosomes are not observed for chromosomal replication and that the mioC gene and gene product is of little importance for the control of initiation. The data demonstrate that a minichromosome is not necessarily a valid model for chromosomal replication. PMID- 1620599 TI - Presence of distinct transcriptional regulatory elements in the 5'-flanking region shared by the chicken H3 histone gene homopair. AB - The chicken H3 histone gene family contains nine members belonging to two major histone gene clusters. Six of these genes have been sequenced and shown to encode two different H3 protein variants. Five H3 genes (H3-I, -II, -IV, -V, and -VI) encode the same amino acid sequence (class I) and another H3 gene (H3-III) differs from class I in a single amino acid (IIe113-Met) (class II). H3-II and H3 III have inverted orientations and share a 5' intergenic region of about 900 bp. To understand the regulation of expression of these two genes, we fused the 5' flanking region to the CAT gene in inverted orientations to generate two chimeric plasmids, pH3-II-900 and pH3-III-900. Transient CAT assays using these constructs indicated that the promoter of H3-III is more active than that of H3-II. CAT assays with deletion mutants showed that H3-II and H3-III each possess a particular transcription regulatory sequence 5' adjacent to their coding sequence. In addition, the functional sequences of H3-II have no effect on expression of H3-III and vice versa. These results suggest that the regulations of expression of the two H3 genes are distinct. PMID- 1620600 TI - Extension of the DNA binding consensus of the chicken c-Myb and v-Myb proteins. AB - The chicken c-myb gene and the v-myb oncogene transduced by avian myeloblastosis virus (AMV) encode DNA binding transcription activators. The DNA binding domain of AMV v-Myb displays a number of amino acid changes relative to c-Myb; v-Myb proteins in which one or more of three crucial residues in the DNA binding domain are mutated to resemble the c-Myb sequence display altered transformation phenotypes. In order to establish whether the spectrum of DNA binding sites which AMV v-Myb can recognise is different from that seen by chicken c-Myb, a site selection protocol was used to derive consensus binding sequences for three variant Myb proteins made in vitro, and also using nuclear extract from the v-myb transformed cell line BM2. The results show that the original consensus binding site defined for v-Myb, YAA-CKG, can be extended to YAACKGHH, and that this new consensus holds for both v-Myb and chicken c-Myb. PMID- 1620601 TI - A sequence element associated with the Plasmodium falciparum KAHRP gene is the site of developmentally regulated protein-DNA interactions. AB - The Plasmodium falciparum gene encoding the knob associated histidine-rich protein (KAHRP) is shown to be transcriptionally regulated during its expression in the intraerythrocytic cycle as demonstrated by stage specific nuclear run-on analysis. The genomic organization of the KAHRP gene was determined and the structural basis for the stage specific transcription investigated. A sequence motif with two-fold symmetry was found 160 bp upstream of the RNA initiation site. This sequence element interacts with parasite derived nuclear extracts in a stage specific manner that correlates with the transcriptional activity of the KAHRP gene. These studies suggest a functional role for this structural element in the developmental regulation of a P. falciparum erythrocytic gene. PMID- 1620602 TI - Chromosome-size variation in Giardia lamblia: the role of rDNA repeats. AB - Giardia lamblia trophozoites contain at least five sets of chromosomes that have been categorized by chromosome-specific probes. Pulsed field separations of G. lamblia chromosomes also demonstrated minor bands in some isolates which stained less intensely with ethidium than the major chromosomal bands. Two of the minor bands of the E11 clone of the ISR isolate, MBa and MBb, were similar to each other and to chromosomal band I by hybridization to total chromosomal DNA and by hybridization of specific probes. In order to determine the extent of this similarity, I have developed a panel of probes for many of the Pacl restriction fragments and have shown that most of the Pacl and Notl fragments found in MBa are also present in MBb. The differences are found in both telomeric regions. At one end, MBb contains a 300 kb region not found in MBa. At the other end of MBb is a 160 kb region containing the rDNA repeats which is bounded on one end by the telomeric repeat and on the other by sites for multiple enzymes that do not digest the rDNA repeats. The corresponding region of MBa is 23 kb in size. The size difference is consistent with the eightfold greater number of rDNA repeats in MBb than MBa and suggests that 30% of the size difference is accounted for by different numbers of copies of the rDNA repeat. MBa of another ISR clone (ISR G5) is 150 kb larger in size than MBa of ISR E11. The data suggest that MBa and MBb are homologous chromosomes of different sizes and that a portion of the size difference is accounted for by different copy numbers of the rDNA repeat. PMID- 1620603 TI - Dbp73D, a Drosophila gene expressed in ovary, encodes a novel D-E-A-D box protein. AB - Proteins of the D-E-A-D family of putative ATP-dependent RNA helicases have been implicated in translation initiation and RNA splicing in a variety of organisms from E. coli to man. The Drosophila vasa protein, a member of this family, is required in the female germ line for fertility and for specification of germ line and posterior positional information in progeny embryos. We report the isolation of another D-E-A-D gene from Drosophila, which, like vasa, is expressed in germ line tissue. The predicted amino acid sequence of this new gene, Dbp73D, contains all of the highly conserved helicase motifs, but is otherwise the farthest diverged member of the family so far identified. PMID- 1620604 TI - Transgenic mice generated by pronuclear injection of a yeast artificial chromosome. AB - Transgenic mice have become invaluable for analysing gene function and regulation in vivo. However, the size of constructs injected has been limited by the cloning capacity of conventional vectors, a constraint that could be overcome with yeast artificial chromosomes (YACs). We investigated the feasibility of making transgenic mice with YACs by pronuclear injection of a small YAC carrying a gene encoding tyrosinase. Use of a vector with a conditional centromere allowed fifteenfold amplification of the YAC in yeast and its recovery in high yield. The albino phenotype of the recipient mice was rescued demonstrating the correct expression of the tyrosine gene from the construct. Furthermore, the telomeric sequences added by the yeast integrated into the mouse genome and did not reduce efficiency of integration. Using this technique future experiments with longer YACs will allow the expression of gene complexes such as Hox and the globin gene clusters to be analysed in transgenic animals. PMID- 1620606 TI - The c4 repressor of bacteriophage P1 is a processed 77 base antisense RNA. AB - The c4 repressors of the temperate bacteriophages P1 and P7 inhibit antirepressor synthesis and are essential for establishment and maintenance of lysogeny. Using in vivo complementation tests we have previously shown that c4 is an antisense RNA acting on a target, ant mRNA, which is transcribed from the same promoter. Here we identify the c4 repressor molecule of P1 as a 77 +/- 1 base RNA by mapping its termini and show that the c4 RNA in P7 lysogens has the same or a similar size. P1 c4 RNA is encoded in a region shown to be sufficient for c4 complementation. It covers exactly the 74 bases previously suggested to fold into a stem-loop secondary structure essential for c4 function. Furthermore, we demonstrate that the 5' end of c4 RNA is generated by processing. Thus, c4 is the first example of an antisense RNA to be processed. A possible mechanism of processing is discussed. PMID- 1620605 TI - Biological properties of imidazole ring-opened N7-methylguanine in M13mp18 phage DNA. AB - Guanine residues methylated at the N-7 position (7-MeGua) are susceptible to cleavage of the imidazole ring yielding 2,6-diamino-4-hydroxy-5N-methyl formamidopyrimidine (Fapy-7-MeGua). The presence of Fapy-7-MeGua in DNA template causes stops in DNA synthesis in vitro by E. coli DNA polymerase I. The biological consequences of Fapy-7-MeGua lesions for survival and mutagenesis were investigated using single-stranded M13mp18 phage DNA. Fapy-7-MeGua lesions were generated in vitro in phage DNA by dimethylsulfate (DMS) methylation and subsequent ring opening of 7-MeGua by treatment with NaOH (DMS-base). The presence of Fapy-7-MeGua residues in M13 phage DNA correlated with a significant decrease in transfection efficiency and an increase in mutation frequency in the lacZ gene, when transfected into SOS-induced JM105 E.coli cells. Sequencing analysis revealed unexpectedly, that mutation rate at guanine sites was only slightly increased, suggesting that Fapy-7-MeGua was not responsible for the overall increase in the mutagenic frequency of DMS-base treated DNA. In contrast, mutation frequency at adenine sites yielding A----G transitions was the most frequent event, 60-fold increased over DMS induced mutations. These results show that treatment with alkali of methylated single-stranded DNA generates a mutagenic adenine derivative, which mispairs with cytosine in SOS induced bacteria. The results also imply that the Fapy-7-MeGua in E. coli cells is primarily a lethal lesion. PMID- 1620607 TI - The liver-specific promoter of the human insulin-like growth factor II gene is activated by CCAAT/enhancer binding protein (C/EBP). AB - The human gene coding for insulin-like growth factor II (IGF-II) contains four promoters (P1-P4), that are subjected to tissue-specific and development dependent regulation. Expression of promoter P1 is detected only in adult liver tissue, whereas promoter P3 is the major IGF-II promoter in fetal liver and is further expressed in other fetal tissues and in adult non-hepatic tissues. C/EBP is a tissue- and development-specific transcription factor that is expressed predominantly in adult liver, adipose tissue and lung. The effect of C/EBP on the expression of constructs containing IGF-II promoter P1 or P3 linked to the luciferase gene was investigated in cotransfection assays using Hep3B cells. We found that promoter P1 can be activated by C/EBP, whereas this transcription factor has no effect on the expression of promoter P3. By gel retardation and DNasel footprinting it was demonstrated that C/EBP can bind to a region of P1 located between 82 and 109 basepairs upstream of the cap site. Furthermore, we showed that deletion of this C/EBP binding region strongly reduces the ability of C/EBP to stimulate transcription from P1. These results indicate that C/EBP is a major component in the specific activation of the human IGF-II promoter P1 in adult liver. PMID- 1620609 TI - Joints formed by RecA protein from oligonucleotides and duplex DNA block initiation and elongation of transcription. AB - In the presence of the non-hydrolyzable analog of ATP, ATP gamma S, RecA protein can polymerize on an oligodeoxy-ribonucleotide to form a stable oligonucleoprotein filament that can find its homologous sequence in double stranded DNA. The homologous joint formed by the oligonucleotide and duplex DNA is stable only if RecA protein is not removed. Such a nucleoprotein joint, covering a part or all of the promoter region of T3 or T7 phage RNA polymerase, blocked transcription directed by those polymerases. The same kind of joint, located downstream of the RNA polymerase promoter, also inhibited elongation of transcription and caused accumulation of truncated transcripts. These observations suggest that RecA protein can be used to shut off transcription from any promoter of known sequence. PMID- 1620608 TI - Two cytotoxic cell proteinase genes are differentially sensitive to sodium butyrate. AB - The 5'-flanking regions of two cytotoxic cell protease genes, CCP1 and 2, are sufficient to confer cytotoxic T lymphocyte-specific expression when fused to a reporter gene. The two regulatory regions are, however, differentially sensitive to treatment of the recipient cell, MTL 2.8.2, with sodium butyrate. With CCP1 a six-fold increase in cat expression was observed, whereas CCP2 was insensitive to the butyrate treatment. One major butyrate-sensitive regions was defined in the CCP1 5'-flanking sequence between -243 to -112 and another less effective one between-682 to -427. These fragments of DNA were also able to confer responsiveness to butyrate when ligated to a heterologous fos promoter. These sequences within the 5' flank of CCP1 share homology with other elements that have been defined as butyrate-responsive. We believe that our results argue against a pleiotropic affect of butyrate such as histone acetylation. More likely sodium butyrate is mediating a specific stimulation of transcription through modification of the activities of selected transcriptional regulatory proteins that in turn affect their interactions with proteins bound to the promoter. PMID- 1620610 TI - Generating compatible translation initiation regions for heterologous gene expression in Escherichia coli by exhaustive periShine-Dalgarno mutagenesis. Human glutathione reductase cDNA as a model. AB - Adaptation of eucaryotic cDNA to heterologous expression was studied by mutating the translation initiation (TI) region upstream (mTI) and downstream (MTI) of the start codon. In the mTI subregion the 8 bases flanking the invariant Shine Dalgarno motif GG-AG were mutagenized exhaustively, while the MTI subregion was subjected to random silent mutations at the wobble positions. The quality of a given TI sequence was judged on the basis of expressed enzyme activity. Low-yield and high-yield mutants of both TI subregions were selected and recombined systematically. The analysis of these double cartridges gave the following results: 1. As a rule, an unfavourable MTI subregion can be compensated for by mutations in the mTI subregion and vice versa. 2. The compatibility between mTI and MTI subregion is explainable at least in part by a low interaction tendency; a delta G(o)'-value of -10.7 kcal/mol appears to be a physical threshold for heterologous cDNA expression. 3. On the basis of periShine-Dalgarno mutations, the expression yield for different cDNA sequences could be increased by 1 to 2 orders of magnitude. One of these sequences encoded delta(1-15)human glutathione reductase, a mutant lacking the flexible N-terminal extension of the protein. In conclusion, to study and overcome TI region-based expression problems it is worthwhile to start out with a versatile vector containing exhaustive mutations in the periShine-Dalgarno sequences; as a rule the coding MTI subregion can be kept unchanged. PMID- 1620611 TI - Mitotic recombination of yeast artificial chromosomes. AB - Large regions of human DNA can be cloned and mapped in yeast artificial chromosomes (YACs). Overlapping YAC clones can be used in order to reconstruct genomic segments in vivo by meiotic recombination. This is of importance for reconstruction of a long gene or a gene complex. In this work we have taken advantage of yeast protoplast fusion to generate isosexual diploids followed by mitotic crossing-over, and show that it can be an alternative simple strategy for recombining YACs. Integrative transformation of one of the parent strains with the construct pRAN4 (containing the ADE2 gene) is used to disrupt the URA3 gene contained within the pYAC4 vector arm, providing the markers required for forcing fusion and detecting recombination. All steps can be carried out within the commonly used AB1380 host strain without the requirement for micromanipulation. The method was applied to YAC clones from the human MHC and resulted in the reconstruction of a 650 kb long single clone containing 18 known genes from the MHC class II region. PMID- 1620612 TI - Quantitation of transient gene expression after electroporation. AB - The combination of a photometric reporter-gene assay, with transfection by electroporation, is potentially a rapid and sensitive tool for the study of genetic regulatory elements in many types of cells. We have found that the sensitivity, accuracy, and reproducibility of the technique is greatly improved by the inclusion of appropriately chosen carrier DNA as the primary DNA species present during electroporation. By using high levels of carrier, the activities of constructs of differing sizes can be quantitatively compared, active constructs can be assayed with sub-microgram amounts of plasmid, and the activities of the constructs are linear over a wide concentration of DNA. In addition, the activity of miniprep DNA can be screened without purification on CsCl gradients giving activities equal to CsCl-purified DNA. This is extremely useful when doing preliminary screening of large numbers of constructs for promoter or enhancer activities. We report the results of testing various types of DNA as carrier, and the parameters for optimizing its use. PMID- 1620613 TI - DNA sequence selectivity of guanine-N7 alkylation by nitrogen mustards is preserved in intact cells. AB - Nitrogen mustard alkylating agents react with isolated DNA in a sequence selective manner, and the substituent attached to the drug reactive group can impose a distinct sequence preference. It is not clear however to what extent the observed DNA sequence preferences are preserved in intact cells. The highly reiterated sequence of human alpha DNA has been used to determine the sites of guanine-N7 alkylation following treatment of cells with three nitrogen mustards, mechlorethamine, uracil mustard and quinacrine mustard, known to react in isolated DNA with distinctly different sequence preferences. Alpha DNA from drug treated cells was extracted, purified, end-labeled, and a 296 base pair, singly end-labelled, fragment isolated. Following the quantitative conversion of alkylation sites to strand breaks the fragments were separated on DNA sequencing gels. Clear differences were observed between the alkylation patterns of the three compounds, and the selectivities were qualitatively similar to those predicted and observed in the same sequence alkylated in vitro. In particular the unique preferences of uracil and quinacrine mustards for 5'-PyGC-3' and 5'-GT/GPu 3' sequences, respectively, were preserved in intact cells suggesting that the pattern of sequence dependent reactivity is not grossly affected by the nuclear milieu. PMID- 1620614 TI - Type 1 ribosome-inactivating proteins depurinate plant 25S rRNA without species specificity. AB - Four different type 1 ribosome-inactivating proteins (RIPs) with RNA N glycosidase activity were tested for their ability to attack the large rRNA of plant ribosomes derived from tobacco plants, as well as from the plant species from which the particular RIP had been isolated. Incubation of tobacco ribosomes with RIPs isolated from either Phytolacca americana L. (pokeweed), Dianthus barbatus L. (carnation), Spinacia oleracea L. (spinach) or Chenopodium amaranthicolor Coste and Reyn. (chenopodium) rendered the 25S rRNA sensitive to aniline-catalyzed hydrolysis, generating a single rRNA-fragment of about 350 nucleotides. The same fragment was generated when rRNAs from pokeweed, carnation, spinach or chenopodium ribosomes were aniline-treated without any deliberate treatment of the ribosomes with the respective RIP. This indicated that ribosomes from all RIP-producing plants were already inactivated by their own RIPs during preparation. These results demonstrate that plant ribosomes are generally susceptible to RIP attack, including modification by their own RIPs. Direct sequencing of the newly generated fragments revealed that a single N-glycosidic bond at an adenosine residue within the highly conserved sequence 5'-AGUACGAGAGGA 3' was cleaved by all of the RIPs investigated, a situation also found in animal, yeast and Escherichia coli ribosomes. PMID- 1620615 TI - Characterization of the testes-specific pim-1 transcript in rat. AB - The pim-1 proto-oncogene encodes a serine/threonine protein kinase and is expressed in cells of hematolymphoid origin and in the germ cell lineages. In somatic cells, the pim-1 gene is expressed as a 2.8 kb transcript while a shorter sized transcript (2.3 kb) is expressed in rat testes. We have determined that the shorter testes-specific pim-1 transcript arises through the use of an alternate polyadenylation signal present in the 3' untranslated region of the gene. This alternate polyadenylation event results in the removal of an A/U-rich regulatory element located in the 3' untranslated region of the pim-1 gene. This A/U-rich motif has been shown by a number of laboratories to destabilize the transcripts of genes that contain this sequence. Consistent with these findings, we have demonstrated that the shortened testes-specific pim-1 transcript is more stable than the longer A/U-rich containing somatic transcript. We suggest that the functional significance of different sized pim-1 transcripts may be directly related to their different stabilities and that the greater stability of the testes-specific transcript may be essential for the translational delay observed in post-meiotic male germ cells. PMID- 1620616 TI - Intron requirement for expression of the human purine nucleoside phosphorylase gene. AB - Abbreviated purine nucleoside phosphorylase (PNP) genes were engineered to determine the effect of introns on human PNP gene expression. PNP minigenes containing the first intron (complete or shortened from 2.9 kb down to 855 bp), the first two introns or all five PNP introns resulted in substantial human PNP isozyme expression after transient transfection of murine NIH 3T3 cells. Low level human PNP activity was observed after transfection with a PNP minigene containing the last three introns. An intronless PNP minigene construct containing the PNP cDNA fused to genomic flanking sequences resulted in undetectable human PNP activity. Heterogeneous, stable NIH 3T3 transfectants of intron-containing PNP minigenes (verified by Southern analysis), expressed high levels of PNP activity and contained appropriately processed 1.7 kb message visualized by northern analysis. Stable transfectants of the intronless PNP minigene (40-45 copies per haploid genome) contained no detectable human PNP isozyme or mRNA. Insertion of the 855 bp shortened intron 1 sequence in either orientation upstream or downstream of a chimeric PNP promoter-bacterial chloramphenicol acetyltransferase (CAT) gene resulted in a several-fold increase in CAT expression in comparison with the parental PNP-CAT construct. We conclude that human PNP gene expression at the mRNA and protein level is dependent on the presence of intronic sequences and that the level of PNP expression varies directly with the number of introns included. The disproportionately greatest effect of intron 1 can be explained by the presence of an enhancer-like element retained in the shortened 855 bp intron 1 sequence. PMID- 1620617 TI - Gene clusters for ribosomal proteins in the mitochondrial genome of a liverwort, Marchantia polymorpha. AB - We detected 16 genes for ribosomal proteins in the complete sequence of the mitochondrial DNA from a liverwort, Marchantia polymorpha. The genes formed two major clusters, rps12-rps7 and rps10-rpl2-rps19-rps3-rpl16-rpl5- rps14-rps8- rpl6 rps13-rps11-rps1, very similar in organization to Escherichia coli ribosomal protein operons (str and S10-spc-alpha operons, respectively). In contrast, rps2 and rps4 genes were located separately in the liverwort mitochondrial genome (the latter was part of the alpha operon in E. coli). Furthermore, several ribosomal proteins encoded by the liverwort mitochondrial genome differed substantially in size from their counterparts in E. coli and liverwort chloroplast. PMID- 1620618 TI - The distribution of 5-methylcytosine in the nuclear genome of plants. AB - We have determined the 5-methylcytosine (5mC) content in high molecular weight DNA, from two dicot (tobacco and pea) and two monocot (wheat and maize) plant species, fractionated according to base composition. The results show that the proportion of 5mC in the genomic fractions increases linearly with their guanine + cytosine (G + C) content while the proportion of non-methylated cytosine remains almost constant. This can be interpreted as a consequence of a difference in mutation pressure related to spontaneous deamination of 5mC to thymine between the different compartments of plant genomes. PMID- 1620619 TI - Purification of components required for accurate transcription of ribosomal RNA from Acanthamoeba castellanii. AB - The components required for specific transcription of ribosomal RNA were isolated from logarithmically growing Acanthamoeba castellanii. The transcription initiation factor fraction, TIF, and RNA polymerase I were extracted from whole cells at 0.35 M KCl. The extract was fractionated with polyethylenimine, then chromatographed on phosphocellulose (P11) which resulted in the separation of TIF from RNA polymerase I. The fractions containing TIF were further chromatographed on DEAE cellulose (DE52), Heparin Affigel, and Matrex green agarose, followed by sedimentation through glycerol gradients. TIF was purified approximately 17,000 fold, and shown to have a native molecular weight of 289 kD, and to bind specifically to rRNA promoter sequences by DNase I footprinting. The addition of homogeneous RNA polymerase I to this complex permitted the initiation of specific transcription in vitro. The phosphocellulose fractions containing RNA polymerase I were chromatographed on DEAE cellulose, Heparin-Sepharose, DEAE-Sephadex, and sedimented through sucrose gradients. Polymerase I was purified to apparent homogeneity with a yield of 8.1% and a specific activity of 315. It contained one fewer subunit than previously reported. DNase I protection experiments demonstrated that in both partially purified and homogeneous fractions, RNA polymerase I was capable of stable binding to the TIF-rDNA complex, and correctly initiating transcription on rDNA templates. PMID- 1620620 TI - Binding of the EcoRII methyltransferase to 5-fluorocytosine-containing DNA. Isolation of a bound peptide. AB - The properties of the interaction of 5-fluorocytosine-containing DNA with the EcoRII methyltransferase were studied. The DNA used was either a polymer synthesized in vitro, or a 20-mer containing one CCA/TGG sequence. The DNA could be methylated by the enzyme. In the process the enzyme formed a tight binding adduct with the DNA that could be identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Enzyme activity was inhibited by this interaction. The 20-mer could be used to titrate the active site of the enzyme. The DNA polymer formed a tight binding complex that could be identified following digestion of the DNA with pancreatic deoxyribonuclease or micrococcal nuclease. A peptide-DNA adduct could be isolated after digestion of the EcoRII-DNA adduct with staphylococcal protease V8 by high pressure liquid chromatography and polyacrylamide gel electrophoresis. Sequencing of the peptide indicated the DNA bound to a region of the protein that is conserved in all procaryotic DNA(cytosine-5)-methyltransferases. We have previously shown that this region contains a cysteine that can be photomethylated with adenosylmethionine. This region, in addition to forming part of, or being adjacent to, the AdoMet binding site, also forms part of the DNA binding site. PMID- 1620621 TI - Complete nucleotide sequence of a neuropathogenic variant of Friend murine leukemia virus PVC-211. PMID- 1620622 TI - RNA polymerase II initiation factor alpha from rat liver is almost identical to human TFIIB. PMID- 1620623 TI - The cohesive ends of mycobacteriophage L5 DNA. PMID- 1620624 TI - Numbering system for the hammerhead. PMID- 1620625 TI - The INO2 gene of Saccharomyces cerevisiae encodes a helix-loop-helix protein that is required for activation of phospholipid synthesis. PMID- 1620626 TI - Application of galactose-sensitive E. coli strains as selective hosts for LacZ- plasmids. PMID- 1620627 TI - The use of uracil-N-glycosylase in the preparation of PCR products for direct sequencing. PMID- 1620628 TI - Mapping of mRNA isoforms with an oligonucleotide probe: exonuclease VII compared with endonucleases. PMID- 1620630 TI - P9: advocacy. Part (i): The 'what' and 'when' of advocacy. PMID- 1620631 TI - Rebuilding the centre. PMID- 1620633 TI - Conflict of interest. PMID- 1620632 TI - Rationing care? PMID- 1620634 TI - How to help the child. PMID- 1620629 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1620635 TI - Goodbye to Rambo. PMID- 1620636 TI - Decision time for midwives. PMID- 1620637 TI - Consumers, continuity and control. PMID- 1620638 TI - Primary panacea? PMID- 1620639 TI - Home is best. PMID- 1620640 TI - Project 2000--research on its implementation. AB - Project 2000 is a major innovation in the preparation of pre-registration nurses. It introduces a Common Foundation Programme with specialisation after 18 months, increased links with higher education, supernumerary status and bursaries for students and a diploma level qualification. This paper is concerned with research design and management issues emerging from the NFER study of the implementation of Project 2000. PMID- 1620641 TI - Working up a thirst. PMID- 1620642 TI - Finding their own way. PMID- 1620643 TI - A sense of duty. PMID- 1620644 TI - Involving nurses in prison therapy. PMID- 1620645 TI - Conversion blues. PMID- 1620646 TI - Taking women seriously. PMID- 1620647 TI - Reducing the risk of assault. PMID- 1620648 TI - Unacceptable advances. PMID- 1620649 TI - Impairment of cold-induced increase in thyroxine 5'-deiodinase activity in mouse brown adipose tissue by the intracerebroventricular administration of bombesin. AB - Effects of bombesin on brown adipose tissue (BAT) thyroxine (T4) 5'-deiodinase (5'D) activity and rectal temperature were examined in male mice. Immediately following an intracerebroventricular (ICV) or intravenous (IV) injection of bombesin (0.1-100 ng/animal) or vehicle (20 mM bacitracin dissolved in 0.9% saline), the mice were placed in a room at 4 degrees C or 22 degrees C for 30, 60, 120 or 240 min. The ICV injection of bombesin dose-dependently lessened cold induced increase in BAT 5'D activity and increased hypothermia determined at 120 min of cold exposure, whereas the IV injection of bombesin was without effect. Bombesin (ICV)-induced hypothermia preceded the inhibition of BAT 5'D activity by at least 30 min at 4 degrees C. BAT 5'D activity was not affected by ICV injection of bombesin in mice kept at 22 degrees C, although the rectal temperature was significantly decreased. Bombesin thus appears to prevent cold induced increase in T4 5'D activity in mouse BAT by its central effect. Bombesin induced excessive hypothermia itself and/or the decrease in sympathetic tone of BAT by bombesin might decrease cold-induced increase in BAT 5'D activity. PMID- 1620650 TI - The levels and biologic action of the human neutrophil granule peptide HP-1 in lung tumors. AB - HP-1 is the most abundant human representative of a recently discovered class of neutrophil cystine- and arginine-rich peptides. These peptides have many potentially regulatory activities expressed at nanomolar concentrations. To establish the levels of HP-1 that can accumulate in human lung tumors and nondiseased lung fragments, tissues were extracted for their peptide content. The extracts were purified on reverse phase HPLC, and HP-1 and related peptides were identified by sequence analysis and their concentrations in the tissue quantitated by amino acid analysis. Immunohistochemistry was performed and strongly suggests that HP-1 is confined to granulocytes under most circumstances, and indicates that the levels of HP-1 measured in the tumors reflect the levels obtained when solid tissue is infiltrated by neutrophils. The maximum observed levels were 26 nanomoles per gram wet weight of tissue. Attempts were then made to correlate this level to the cytotoxic potential of HP-1 by performing in vitro cytotoxicity dose-response curves on several cell lines. Most cells were killed at between 1 and 8 microM, and the response depended on the growth conditions of the cells. The levels of HP-1 that accumulate in tumors can exceed the in vitro cytolytic concentrations. The levels are also considerably in excess of those required to exert in vitro regulatory actions. PMID- 1620651 TI - Effects of BCH 325 (Pro-D-Phe-Pro-Gly) on open field behavior after chronic stress procedure. AB - The chronic stress model is an animal model relevant to clinical depression. The chronic stress rat group showed a significant decrease in motor activity. The reduced open field activity could be restored by subchronic treatment with imipramine and doxepine. Subchronic treatment with haloperidol, amphetamine and methylglucamine orotate was not able to alter the reduced open field activity. Previous treatment with a beta-casomorphin derivative (BCH 325) significantly antagonized the effect of chronic stress. The findings point out an antidepressant-like effect of BCH 325. PMID- 1620652 TI - Primary structure of frog PYY: implications for the molecular evolution of the pancreatic polypeptide family. AB - A peptide belonging to the pancreatic polypeptide (PP) family was isolated in pure form from the intestine of the European green frog (Rana ridibunda). The primary structure of the peptide was established as: Tyr-Pro-Pro-Lys-Pro-Glu-Asn Pro-Gly-Glu10-Asp-Ala- Ser-Pro-Glu-Glu-Met-Thr-Lys-Tyr20-Leu-Thr-Ala-Leu-Arg-His Tyr-Ile- Asn-Leu30-Val - Thr-Arg-Gln-Arg-Tyr-NH2. This amino acid sequence shows moderate structural similarity to human PYY (75% identity) but stronger similarity to the PP family peptides isolated from the pancreas of the salmon (86%) and dogfish (83%). The data suggest that the two putative duplications of an ancestral PP family gene that have given rise to PP, PYY and NPY in mammals had already taken place by the time of the appearance of the amphibia. In fish, however, only a single duplication has occurred, giving rise to NPY in nervous tissue and a PYY-related peptide in both pancreas and gut. PMID- 1620653 TI - Effects of CCK antagonists on CCK-induced suppression of locomotor activity in mice. AB - Sulfated cholecystokinin octapeptide (CCK-8) was administered either intraperitoneally or into the cerebral ventricle of fully conscious mice, and locomotor activity was quantified. CCK-8 administered by either route suppressed locomotor activity. Subcutaneously administered selective CCK-A receptor antagonist, L-364,718 (1 mg/kg), reversed the inhibitory effect of centrally as well as peripherally administered CCK-8, but the selective CCK-B receptor antagonist, L-365,260 (1 mg/kg), did not. These results demonstrate that centrally as well as peripherally administered CCK-8 suppresses locomotor activity in mice through an interaction with CCK-A, but not CCK-B, receptors. PMID- 1620654 TI - Activation of CCK-A receptors induces elevation of plasma corticosterone in rats. AB - Cholecystokinin octapeptide (CCK-8) and ceruletide (1 microgram/kg) produced a pronounced increment of plasma corticosterone levels at 30 min after intraperitoneal administration. The response to these peptides was suppressed by pretreatment with a selective antagonist for CCK-A receptors, (-)L-364,718, in a dose-related manner, but not with an antagonist for CCK-B receptors, (+)L 365,260. However, (-)L-364,718 itself had no effect on basal levels of plasma corticosterone. These results indicate that peripheral administration of CCK-8 and ceruletide stimulates the hypothalamo-pituitary adrenal axis through the activation of CCK-A receptors, but not CCK-B receptors. PMID- 1620655 TI - Gonadotropin-releasing hormone in elasmobranch (electric ray, Torpedo marmorata) brain and plasma: chromatographic and immunological evidence for chicken GnRH II and novel molecular forms. AB - Gonadotropin-releasing hormone (GnRH) peptides in the brain, testis and plasma of an electric ray (Torpedo marmorata) were investigated by gel filtration chromatography, reverse phase high performance liquid chromatography and radioimmunoassay with region-specific antisera. In the brain, two major forms of GnRH were demonstrated. One form had identical chromatographic and immunological properties to chicken GnRH II, and the second, novel, molecular form had structural features in common with mammalian, chicken II and salmon GnRHs. A minor, early-eluting immunoreactive peak, possibly also a novel GnRH, was also evident. Immunoreactive GnRH was not detected in the testis. In the plasma, a single major early-eluting immunoreactive peak was demonstrated. This peak, identical to the minor peak observed in the brain, is likely to represent a novel form of GnRH which has immunological properties in common with mammalian, chicken II and salmon GnRHs. Immunoreactive GnRH was not detected in the plasma of species from other vertebrate classes, including rabbit, chicken, monitor lizard, clawed toad, frog, cichlid fish and lamprey. The finding of chicken GnRH II in a species of Chondrichthyes adds further support to our hypothesis that this widespread structural variant may represent an early-evolved and conserved form of GnRH. The presence of a GnRH molecular form in the plasma of the electric ray suggests that GnRH may reach target organs (pituitary and gonads) via the general circulation in some species of Chondrichthyes. PMID- 1620656 TI - In vitro penetration of des-tyrosine1-D-phenylalanine3-beta-casomorphin across the blood-brain barrier. AB - The blood-brain barrier transport and metabolism of the synthetic beta casomorphin (beta CM) derivative des-tyrosine1-D-phenylalanine3-beta-casomorphin (DT-D-Phe3-beta CM) were investigated using an in vitro model consisting of primary cultures of bovine cerebrovascular endothelial cells. DT-D-Phe3-beta CM was transported across the endothelial monolayer without significant metabolism. The endothelial permeability expressing the transport rate ranged between 1.4 and 2.2 cm x 10(-3)/min and was neither affected by luminal concentration changes (1 nM and 1 microM) nor different after luminal and abluminal administration. The metabolic inhibitor 2-desoxy-D-glucose did not affect the permeability of DT-D Phe3-beta CM. These results suggest that DT-D-Phe3-beta CM is able to cross the blood-brain barrier by paracellular transport without using a carrier system. PMID- 1620657 TI - Prolonged antinociceptive activity of pseudodipeptide analogues of Lys-Trp(Nps) and Trp(Nps)-Lys. AB - Peptide bond substitution in the molecules of Lys-Trp(Nps) (LTN) and Trp(Nps)-Lys (TNL) by an aminomethylene and ketomethylene bond, respectively, afforded pseudodipeptides with analgesic activity. The new compounds Lys psi(CH2NH) Trp(Nps)-OMe (LTNAM) and Trp(Nps)psi(COCH2)(R,S)-Lys (TNLKM) induced a dose dependent and naloxone-reversible analgesia following intracerebroventricular (ICV) administration to mice. The antinociceptive effects were longer lasting compared to those induced by the parent compounds. The pseudodipeptides protected Met-enkephalin degradation by rat striatal slices and, combined with an ineffective dose of the opioid peptide, induced analgesia. LTNAM and TNLKM were as potent as LTN to inhibit brain aminopeptidase in vitro and ex vivo. An increased resistance to proteolysis of the pseudodipeptides may explain their prolonged analgesic activity. PMID- 1620658 TI - Influence of modified casomorphins on yawning behavior of rats. AB - Apomorphine-induced yawning was completely suppressed in animals treated with 5 nmol [D-Pro4]casomorphin (CM) (ICV), 10 nmol [D-Phe3]CM (ICV) or 10 nmol [D Pip4]CM (ICV). The apomorphine-induced yawning was also decreased, by des-Tyr analogs, but only by about 50%. Physostigmine (0.15 mg/kg, IP) induced yawning. The physostigmine-induced yawning was suppressed by 5 nmol [D-Pro4]CM and 10 nmol [D-Phe3]CM. Both [des-Tyr-D-Phe3]CM and [des-Tyr-D-Pip4]CM were without effect, whereas [des-Tyr-D-Pro4]CM increased significantly the physostigmine-induced yawning. The results suggest that dopaminergic transmission can be modulated by beta-casomorphin derivatives, thus resulting in a decrease in yawning. In the case of the des-tyrosine derivatives, we can assume a dopaminergic modulation, too. An increase in serotonergic activity might be supposed for [des-Tyr-D Pro4]CM. PMID- 1620659 TI - dTyr-D-Phe3 (Pro-D-Phe-Pro-Gly) interacts specifically with amygdaloid-kindled seizures and is capable of preventing the learning deficit occurring after kindling. AB - In amygdala-kindled rats a deficit in learning brightness discrimination was found. We concluded that this result provides a reliable basis for creating an animal model of cognitive dysfunctions in epileptics. Recently, a des-tyrosine D amino acid substituted derivative of bovine beta-casein(1-5) was reported to exhibit anticonvulsant as well as antidepressant activity. Therefore, we tested the effect of this peptide on kindled seizures and the learning deficit after kindling. It was found that the peptide suppressed the duration of seizures whereas seizure severity was not influenced. Furthermore, the learning performance of peptide-treated rats was significantly higher than that of kindled controls. PMID- 1620661 TI - The effect of vasoactive intestinal peptide (VIP) and naloxone combination on survival rates in rats exposed to severe hemorrhage. AB - In this experiment, the effects of different doses of vasoactive intestinal peptide (VIP) and naloxone (NLX) combinations on survival rates were investigated in rats exposed to 40% hemorrhage. A combination of 25 ng.kg-1 VIP+5 mg.kg-1 NLX showed the best results on survival. The important prospect of this combination is to have the most potent inhibitory effect on mast cell degranulation. When this combination was given together with shed blood reperfusion and 7.5% NaCl, survival rate increased relative to the administration of shed blood alone and of 7.5% NaCl. These findings suggest that inhibition of mast cell degranulation has a beneficial effect on severe hemorrhage. PMID- 1620660 TI - Peripheral factors in the mediation of cholecystokinin-induced satiety as assessed by comparative potencies of cholecystokinin antagonists. AB - Cholecystokinin COOH-terminal octapeptide (CCK-8) produces a satiating effect in the rat and other animals upon peripheral administration. Although it has been demonstrated that the receptors which mediate this action are located in the periphery and are of the CCK-A subtype, their anatomical location has not been firmly established. A dense population of CCK receptors in the pyloric sphincter has been suggested as a candidate. We here quantify the potency of several CCK antagonists to inhibit the contractile effect of CCK-8 on the rat pyloric sphincter in vitro. The potent and selective antagonist MK-329 has a Schild pK of 8.85; the less potent but selective antagonist lorglumide (CR-1409) a pK of 6.37; the related antagonist phenoxyacetylproglumide (phi oAc proglumide) a pK of 5.1; and the weak parent compound proglumide a pK of about 3.3. These data can be compared with the potencies of these compounds to inhibit the actions of CCK-8 to produce satiety in the rat; this comparison supports the contention that CCK receptors of the rat pyloric sphincter could in part mediate the satiety effect produced by exogenous CCK-8. PMID- 1620662 TI - The behavioral treatment of cigarette smoking. PMID- 1620663 TI - Stages of change in the modification of problem behaviors. PMID- 1620664 TI - A behavioral approach to the prevention of school dropout: conceptual and empirical strategies for children and youth. PMID- 1620665 TI - Body image: extent of disturbance, associated features, theoretical models, assessment methodologies, intervention strategies, and a proposal for a new DSM diagnostic category--body image disorder. PMID- 1620666 TI - Cognitive therapy of personality disorders. PMID- 1620667 TI - Childhood enuresis: etiology, assessment, and current behavioral treatment. PMID- 1620668 TI - Pediatric neurodiagnostic tests: a modern perspective. PMID- 1620669 TI - Office care of wounds. PMID- 1620670 TI - Case 1: Chronic meningococcemia. PMID- 1620671 TI - Case 2: Sepsis with purpura. PMID- 1620672 TI - Case 3: Rocky mountain spotted fever. PMID- 1620673 TI - Diagnosis of the unknown poison. PMID- 1620674 TI - [Reactions and neoplasms of the lymphatic system. On the 76th Congress of the German Society of Pathology 09-13 June 1992]. PMID- 1620675 TI - [Functions of specialized pathologic-anatomic tumor registries]. PMID- 1620676 TI - [Current status of grading in breast cancer]. PMID- 1620677 TI - [Media structure, media width and pressure related elasticity of the carotid sinus in man. A study of the importance of local factors for development of sclerotic plaques]. PMID- 1620678 TI - [Arrhythmogenic right ventricular dysplasia]. PMID- 1620679 TI - [Placental findings in congenital syphilis]. PMID- 1620680 TI - [Exogenous ochronosis after L-dopa treatment]. PMID- 1620681 TI - [Fatal thrombosis of the basilar artery after minor blunt skull and brain injury]. PMID- 1620683 TI - [Niels Stensen (1638-1686)--a universal scientist]. PMID- 1620682 TI - [Congenital rhabdoid tumor in the mediastinum and liver. Case report and review of the literature]. PMID- 1620684 TI - Purifying nuclei. AB - Nuclear isolation methods exist since over 50 years and even today new procedures and amendments of standard methods are published. They can be classified into nonaqueous and aqueous methods. The latter can be subdivided into isotonic, hypertonic and hypotonic systems. In most cases the aqueous isolation renders nuclei closer to their physiological status in the cell. A standard method for the hypotonic isolation of nuclei is presented and the methodology of nuclear isolation is discussed. PMID- 1620685 TI - High resolution of multiple forms of red blood cell enzymes using a Toyopearl DEAE 650 S. AB - We have investigated a new anion exchange chromatographic support (Toyopearl DEAE 650 S) which simultaneously allows easily to remove hemoglobin from hemolysates and to obtain a very high resolution of enzymes present in multiple forms. The results obtained are better than those obtainable using an anion-exchange HPLC column. The data obtained at analytical level suggest a wider use of this new matrix also for preparative purposes without significant changes in the resolution. PMID- 1620686 TI - Preparative purification of pig red blood cell hexokinase type III using a new efficient chromatographic support. AB - In this paper we report the purification of pig erythrocyte hexokinase type III, at preparative level, using 52 liters of starting material (hemolysate). This was possible using a new efficient anion exchanger support, the Toyopearl DEAE 650 M which allows completely to change the strategy of removing hemoglobin from hemolysates, permitting to handle large amounts of starting material and reducing work would have required months using conventional anion exchanger supports, to only 2-3 days. Furthermore, we have tested the binding of other red blood cell enzymes to the Toyopearl DEAE 650 M, showing a wider potential use of this chromatographic support for their purification at a preparative level. PMID- 1620687 TI - Large scale extraction of alpha-lactalbumin and beta-lactoglobulin from bovine whey by precipitation with polyethylene glycol and partitioning in aqueous two phase systems. AB - The milk proteins alpha-lactalbumin and beta-lactoglobulin have been isolated from bovine whey by fractional precipitation with polyethylene glycol (PEG) and hydrophobic partitioning in aqueous PEG-hydroxypropylstarch two-phase systems using PEG-bound palmitate as hydrophobic ligand. The possible use of this combination for large scale purification of these whey proteins is discussed. PMID- 1620688 TI - Purification and characterization of kallikrein-like serine proteases from rat submandibular glands. AB - The purification and characterization of kallikrein-like proteases from rat submandibular glands is described. The proteolytic activity of each fraction during purification was monitored on the synthetic substrate N-alpha-tosyl-L arginine methyl ester (TAME). The purification scheme involved ammonium sulfate precipitation, chromatography on columns of DEAE-Sepharose and Sephadex G-100 and chromatofocusing. Three TAME-hydrolytic activity peaks were eluted from DEAE Sepharose as unbound fraction (Pool 1), at 125 mM NaCl (Pool 2) and at 250 mM NaCl concentration (Pool 4). Pool 1 further resolved into two protease fractions (1A1 and 1A2), pool 2 into three protease fractions (2A1, 2A2 and 2A3) and pool 4 gave a single major protease peak (4A1) by chromatofocusing on PBE-94. Protease pools 2A2, 2A3, and 4A1 each gave a single band on SDS-polyacrylamide gel electrophoresis with an estimated molecular weight of 34 kDa, 46 kDa and 46 kDa respectively. Pools 1A1, 1A2, 2A1 and 2a2 gave a single precipitin line with anti rat glandular kallikrein antibodies. 2A3 and 4A1 did not react with these antibodies. Synthetic substrates DL-val-leu-arg-pNA and Bz-pro-phe-arg-pNA, specific for kallikrein-like proteases, were hydrolyzed preferentially by 2A3 and 4A1 but were poor substrates for 1A1, 1A2, 2A1 and 2A2. PMID- 1620689 TI - Effects of temperature, flow rate and composition of binding buffer on adsorption of mouse monoclonal IgG1 antibodies to protein A Sepharose 4 Fast Flow. AB - The binding capacity of protein A Sepharose 4 Fast Flow for mouse IgG1 monoclonal antibodies (mabs) appears to be highly dependent on the buffer composition with respect to both concentration and ion type. Depending on the particular mab dynamic binding capacities up to 20 mg mab per ml gel could be obtained, when these mabs were isolated from supernatants of protein free hollow fibre cell culture systems. Variation of linear flow rate from 10 up to 300 cm/h and temperature (4 degrees C versus 25 degrees C) had a slight effect on the dynamic binding capacity, when a high ionic strength buffer was used during adsorption. Applying optimum binding conditions, final IgG fractions with a purity of more than 95% monomeric IgG were obtained. However, as side effect of the use of binding buffers with high ionic strength, the binding of acid proteases was also promoted. PMID- 1620690 TI - Two methods to avoid the effect of endogenous protein inhibitors during the assay of protein kinase C activity in tissue extracts. AB - Using H1 as substrate the protein kinase C activity of rat liver cell sap was increased about fourfold by treatment with DEAE-cellulose at pH 7.5 at an intermediate ionic strength due to removal of protein inhibitors. The activity of cell sap from rat spleen, brain or muscle was about doubled by the same treatment. In contrast, when a specific synthetic peptide substrate was used the corresponding increase of enzyme activity was not obtained when the inhibitors were removed. This shows that this type of substrates should be preferred for reliable assays of protein kinase C in crude extracts. The possible role of the protein inhibitors for the substrate specificity of protein kinase C is briefly discussed. PMID- 1620691 TI - Isolation and purification of extracellular matrix vesicles from blood vessels. AB - Extracellular membrane-bound vesicles (called matrix vesicles) which occur in abundance in atherosclerotic blood vessels are believed to be associated with lipid accumulation and calcification. A technique has been developed to isolate them from experimental aneurysms in sheep in which they are known to be plentiful. The matrix vesicles were isolated by differential centrifugation following extraction by hypotonic salt solution. Most of the vesicles were pelleted at 30,000g and fell within the size range of matrix vesicles in situ in the aneurysmal wall. Preliminary characterization of the enzymatic activities indicates that many of these vesicles are formed from cell membranes rather than being derived from lysosomes, mitochondria or endoplasmic reticulum. Morphologically they are similar to matrix vesicles of other mineralizing tissues. PMID- 1620692 TI - Molecular mechanics simulations of a conformational rearrangement of D-xylose in the active site of D-xylose isomerase. AB - A proposed reaction mechanism for the enzyme D-xylose isomerase involves the ring opening of the cyclic substrate with a subsequent conformational rearrangement to an extended open-chain form. Restrained energy minimization was used to simulate the rearrangement. In the ring-opening step, the substrate energy function was gradually altered from a cyclic to an open-chain form, with energy minimization after each change. The protein/sugar contact energy did not increase significantly during the process, showing that there was no steric hindrance to ring opening. The conformational rearrangement involves an alteration in the coordination of the substrate to metal ion [1], which was induced by gradually changing restraints on metal/ligand distances. By allowing varying amounts of flexibility in the protein and examining a simplified model system, the interactions of the sugar with metal ion [1] and its immediate ligands were found to be the most important contributors to the energy barrier for the change. Only small changes in the positions of protein atoms were required. The energy barrier to the rearrangement was estimated to be less than the Arrhenius activation energy for the enzymatic reaction. This is in accordance with experimental indications that the isomerization step is rate determining. PMID- 1620693 TI - Characterization of HIV-1 p24 self-association using analytical affinity chromatography. AB - Analytical affinity chromatography (AAC) was used to detect and quantitate the self-association of p24gag, the major structural capsid protein of human immunodeficiency virus (HIV-1). p24gag was immobilized on a hydrophilic polymer (methacrylate) chromatographic support. The resulting affinity column was able to interact with soluble p24, as judged by the chromatographic retardation of the soluble protein upon isocratic elution under nonchaotropic binding conditions. The variation of elution volume with soluble protein concentration fit to a monomer-dimer model for self-association. The soluble p24-immobilized p24 association process was observed using both frontal and zonal elution AAC at varying pH values; the dissociation constant was 3-4 x 10(-5) M at pH 7. That p24 monomer associates to dimers was determined in solution using analytical ultracentrifugation. The solution Kd was 1.3 x 10(-5) M at pH 7. AAC in the zonal elution mode provides a simple and rapid means to screen for other HIV-1 macromolecules that may interact with p24 as well as for modulators, including antagonists, of HIV p24 protein assembly. PMID- 1620694 TI - Continuum electrostatics of the C-peptide: anatomy of the problem. AB - A computational study of the role of all ionizable groups of the C-peptide in its helix-coil transition is performed within the framework of continuum electrostatics. The method employed in our computations involves a numeric solution of the Poisson equation with the Boundary Element Method. Our calculations correctly predict the experimentally observed trends in the helix coil equilibrium of the C-peptide, and suggest that the mechanisms involved are more complex than usually presumed in the literature. Our results suggest that electrostatic interactions in the unfolded conformation are often more important than in the helix, total electrostatic contribution to the helix-coil transition due to the side chains of the C-peptide destabilizes the helix, changes in the helix stability produced by the changes in the ionization state of the side chains are dominated by side chain effects, the effect of the helix dipole on the energetics of the helix-coil transition of the C-peptide is either minor or similar to other contributions in magnitude; while the formation of a salt bridge is electrostatically favorable, formation of the hydrogen bond between a charged and a polar side chains is not. Factors limiting the accuracy of the computations are discussed. PMID- 1620695 TI - Structural and energetic differences between insertions and substitutions in staphylococcal nuclease. AB - In a previous study, the small protein staphylococcal nuclease was shown to readily accommodate single alanine and glycine insertions, with average losses in stability comparable to substitutions at the same sites (PROT. 7:299-305, 1990). To more fully explore this unexpected adaptability to changes in residue spacing, 2 double amino acid insertions (alanyl-glycine, glycyl-glycine) and 3 additional single amino acid insertions with dissimilar side chains (proline, leucine, and glutamine) were constructed at 10 of the sites previously studied. At 8 of these sites, the type of amino acid side chain on the inserted residue significantly influenced the stability of the mutant protein. However, at 9 of the 10 sites, the double insertions were found to be no more destabilizing than the single alanine or glycine insertions. In contrast, double substitution mutations of staphylococcal nuclease, which replace two adjacent residues with alanine, do not show this striking degree of non-additivity. A comparison of the effects of single glutamine and single glycine insertions with alanyl-glycine insertions indicates that insertion of alanine into the peptide backbone is, on average, less destabilizing than appending the equivalent atoms onto the side chain of a glycine insertion. To explain their very different energetic effects, we propose that, unlike most substitutions, the inserted residue(s) must induce lateral displacements of the polypeptide chain, forcing the folded conformation away from that of wild type. The resulting obligatory shifts in the positioning of residues flanking the insertion generate a large number of degrees of freedom around which the mutant structure can relax.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620697 TI - Crystallization and preliminary X-ray diffraction analysis of staphylococcal enterotoxin type C. AB - The Type C staphylococcal enterotoxin produced by Staphylococcus aureus strain FRI-909 has been crystallized using a combination of two precipitants, ammonium sulfate and polyethylene glycol 400, with the addition of small amounts of detergent. Two related crystal forms have been obtained, one triclinic, and one tetragonal, both with one toxin molecule per asymmetric unit. These crystals are stable for at least 75 hr in the X-ray beam and diffract to at least 2.2 and 2.6 A, respectively. The triclinic crystals have unit cell parameters a = 38.5 A, b = 43.7 A, c = 36.9 A, and interaxial angles alpha = 99.9 degrees, beta = 95.8 degrees, and gamma = 98.5 degrees. The tetragonal crystals are of space group P4(1)22 with unit cell parameters a = 43.4 A and c = 278.0 A. PMID- 1620696 TI - Michaelis complexes of porcine pancreatic elastase with 7-[(alkylcarbamoyl)amino] 4-chloro-3-ethoxyisocoumarins: translational sampling of inhibitor position and kinetic measurements. AB - A step leading to the formation of the covalent complexes between porcine pancreatic elastase (PPE) and 7-[(alkylcarbamoyl)amino]-4-chloro-3 ethoxyisocoumarins (alkylHNCO-EICs) is the formation of the noncovalent Michaelis complex. No average structures are available for the Michaelis complexes of PPE with alkylHNCO-EICs. We present the results of an initial step in obtaining these structures and have determined kinetic constants as well. The kinetic results indicate that formation of the Michaelis complex is what differentiates the effectiveness of these inhibitors in inactivating PPE. The structural and kinetic results together suggest that the structure of the Michaelis complex is necessary for the design of potent alkylHNCO-EIC inhibitors of PPE. Two novel alkylHNCO EICs are predicted to be the best inhibitors of this series. An alternate mechanism for serine protease inhibition is also proposed. Evidence for, and studies that may add support to, the hypothesized mechanism are discussed. PMID- 1620698 TI - Crystallization and preliminary X-ray diffraction studies of two mutants of lactate dehydrogenase from Bacillus stearothermophilus. AB - Bacillus stearothermophilus lactate dehydrogenase, one of the most thermostable bacterial enzymes known, has had its three-dimensional structure solved, the gene coding for it has been cloned, and the protein can be readily overexpressed. Two mutants of the enzyme have been prepared. In one, Arg171 was changed to Trp (R171W) and Gln102 was changed to Arg (Q102R). In the other, the mutation Q102R was maintained, but Arg171 was changed to Tyr (R171Y). In addition, an inadvertent C97G mutant was present. Both mutants have been crystallized by the hanging drop vapor diffusion method at room temperature. Bipyrimidal crystals have been obtained against (NH4)2SO4 in 50 mM piperazine HCl buffer. The crystals belong to space group P6(2)22 (P6(4)22) (whereas the native enzyme, the structure of which has been solved by Piontek et al., Proteins 7:74-92, 1990) crystallized in the space group P6(1)) with a = 102.3 A, c = 168.6 A for the R171W, Q102R, C97G triple mutant, and a = 98.2 A; c = 162.1 A for the R171Y, Q102R, C97G mutant. These crystal forms appear to contain one-quarter of a tetramer (M(r) 135,000) in the asymmetric unit and have VM values of 3.8 and 3.3 A3/dalton, respectively). The R171W mutant diffracts to 2.5 A and the R171 Y mutant to approximately 3.5 A. PMID- 1620699 TI - Activation of the ras oncogene in gamma radiation and neutron radiation induced thymic lymphomas. PMID- 1620700 TI - Experimental models of benzene carcinogenesis. PMID- 1620701 TI - Oxidation and conjugation of aflatoxins by humans and experimental animals. PMID- 1620703 TI - Alkylating agents relating to carcinogenesis in man. PMID- 1620702 TI - Carcinogenic effects of chemotherapeutic compounds. PMID- 1620704 TI - DNA adducts induced by platinum drug chemotherapeutic agents in human tissues. PMID- 1620705 TI - Cancer enhancement by cell proliferation. PMID- 1620706 TI - Phenobarbital and related compounds: approaches to interspecies extrapolation. PMID- 1620707 TI - Multistage hepatocarcinogenesis in the rat: insights into risk estimation. PMID- 1620708 TI - Comparisons of human cancer potency projections for dieldrin based on human data with those based on animal data. PMID- 1620709 TI - Multi-site regulation of estrogen receptor by 2,3,7,8-tetrachlorodibenzo-p dioxin. PMID- 1620710 TI - Specific mechanistic aspects of animal tumor promoters: the okadaic acid pathway. PMID- 1620711 TI - Evaluation of sustained hyperplasia and other short-term tests as predictors of tumorigenic potential in oil products. AB - Some oil products are known to cause skin tumors following long-term application while others do not. The ability to predict which ones might cause tumors is important. Development of reliable short term tests which can accurately predict tumorigenic potential of oil products is needed to avoid the high cost and long time required for traditional animal bioassays. Several short term tests were evaluated for their ability to predict tumorigenic potential of 10 coded oil samples and results were compared to results of mouse bioassays. Analytical determinations of PAC content (DMSO extraction) and 3-6 ring PAC content were also made for each of the 10 samples for further comparison. Tests which showed good correlation with bioassay results and thus were considered good predictors of tumorigenic potential were: Sustained Epidermal Hyperplasia as measured by epidermal thickness, Nuclear Area of epidermal basal cells, Modified Ames Test and DMSO extraction for PAC content. Tests which did not show good correlation with bioassay results and which were not considered good predictors of tumorigenic potential were: Polymorphonuclear leukocyte (PMN) infiltration into the dermis, Unscheduled DNA Synthesis in epidermal cells and Changes in Nuclear DNA Content of CHO cells. PMID- 1620712 TI - Differences in animal and human responses to carcinogenic metals. PMID- 1620713 TI - Animal models of mesothelioma induced by mineral fibers: implications for human risk assessment. PMID- 1620714 TI - Interspecies sensitivity to chemical carcinogens. PMID- 1620715 TI - Animal studies in potency ranking of carcinogens in Norway. PMID- 1620716 TI - Mechanisms of human carcinogens. AB - Mutational mechanisms can be proposed as contributing to the activity of most human carcinogens. Many of these chemicals are electrophilic or are metabolically activated to reactive molecules that can alter DNA. Even human carcinogens that do not exhibit direct chemical interaction with DNA, e.g., hormones and asbestos, have been shown to induce genetic effects when in vitro assays for chromosomal mutations are employed. Since these chemicals are usually inactive in the Salmonella assay and other gene mutational assays, more emphasis has been placed on their nonmutational mechanisms. Evidence exists that these carcinogens alter gene expression and stimulate cell proliferation by epigenetic mechanisms; such properties almost certainly contribute to the carcinogenic activity of these chemicals. Although less well studied, DNA reactive, genotoxic carcinogens also alter gene expression and cell proliferation by epigenetic mechanisms. These findings are consistent with the current understanding of the molecular basis of multistep carcinogenesis. The neoplastic evolution of most common human cancers occurs as the result of multiple mutational events. The molecular basis for these mutations is varied and includes point mutations, deletion mutations, chromosome rearrangements, gene amplification, and chromosome losses and gains. Therefore, different mutational activities of carcinogens may influence the carcinogenic process at different steps. In addition, chemical influences on gene expression and cell proliferation are important in allowing clonal expansion of preneoplastic cells and in disrupting the suppressive effects of surrounding normal cells on preneoplastic cells (Dotto et al., 1988). Therefore, the mechanisms of action of human carcinogens, and very likely many rodent carcinogens, will include both genetic and epigenetic processes. PMID- 1620717 TI - Relevance of quantitation of benzo(a)pyrene metabolites in animal excretes to evaluate individual human cancer risk. PMID- 1620718 TI - Animal models in the assessment of fiber carcinogenesis. PMID- 1620719 TI - DNA adduct formation and aromatic amine tumorigenesis. PMID- 1620720 TI - Benzene dosimetry in experimental animals: relevance for risk assessment. AB - The findings of the studies summarized in this report provide some understanding of the possible role of dosimetry in the different response of the rats and mice to benzene in the long-term bioassay studies. The more sensitive species, the mice, definitely has a higher capacity to metabolize benzene and to metabolize it to more of the putative toxic metabolites than do rats. A major finding of these studies is that in three different animal species, from mice to monkeys, the metabolic pathways leading to production of the putative toxic metabolites appear to be low-capacity, high-affinity pathways that are saturated at relatively low exposure concentrations. This does not prove, but suggests, that the same may be true in humans. If the total formation of the putative toxic metabolites is predictive of the toxicity of benzene, then the animal studies suggest that calculations of the risk associated with low dose exposures based on the results of animal studies conducted at high doses would underestimate the toxicity of benzene. The current report concerns only dosimetry. Another problem in assessing the risk to humans from benzene exposure is the fact that the animal models do not respond to benzene in the same way as humans. The major concern for humans exposed to benzene, based on epidemiology studies, is the risk of developing acute myelogenous leukemia (Rinksy, 1987). The cancers developed by the rodents on the long-term bioassay studies were at other sites (liver, lung, Zymbal's gland, lymph tissue, ovaries, and mammary gland). There is as yet no good animal model for benzene-induced leukemia. However, it has been suggested that benzene may also increase the incidence of Hodgkin's disease, malignant lymphoma, multiple myeloma and lung cancer in humans, although a statistical basis for this is lacking (Askoy, 1985). It is not unreasonable to assume that whatever form of cancer is induced, the induction is most likely through the reactive metabolites produced from benzene. Therefore, the dosimetry of these metabolites is pertinent. Our studies indicate that benzene metabolite dosimetry data obtained in animals provides data relevant to the estimation of human risks. PMID- 1620721 TI - Divergent selection for pentobarbital-induced sleeping times in mice. AB - A pharmacogenetic model for sensitivity of mice to pentobarbital is being developed by selection for sleep-time response. One generation of divergent selection for long and short sleep-time in mice resulted in a 19% increase in the long-sleep line and a 15% decrease in the short-sleep line. Calculated heritability estimates averaged 0.49 and realized heritabilities averaged 0.24. The extent of the selection progress and the heritability values indicate that genetic constitution plays a major role in controlling variations of sleep-time response to pentobarbital. PMID- 1620722 TI - Diamine oxidase activity in the duodenal mucosa of rats with cysteamine-induced ulceration. AB - Cysteamine administration to rats is followed by a high incidence of duodenal ulceration. The effect of cysteamine on the activity of diamine oxidase (DAO, histaminase) in the duodenal mucosa of the rat was investigated. Rats were injected subcutaneously with cysteamine on 2 successive days at doses of 10, 20 and 40 mg/100 g body weight and killed 24 h after the second dose. The results indicated that cysteamine at a dose of 40 mg/100 g body weight inhibited enzyme activity by about 27% (p less than 0.05). Lower doses of cysteamine did not significantly affect enzyme activity. In another experiment, rats were injected subcutaneously with either saline (control) or cysteamine at a single dose of 40 mg/100 g body weight and killed 4, 8, 12, 24, 48 and 60 h thereafter. The ulcerogen produced progressive reductions in enzyme activity, which were significant at 12 h (22% reduction) and 24 h (25% reduction). At 60 h, enzyme activity was not significantly different from that of control. PMID- 1620723 TI - The interconversion of prednisone and prednisolone in human and rabbit organs in vitro is a function of tissue integrity. AB - The interconversion and elimination of prednisone (PO) and prednisolone (POH) were examined in human and rabbit liver, kidney, lung and skeletal muscle preparations to determine the effect of organ disruption on in vitro metabolism within multiple organs of two species. Results from microsomes, homogenates and minces were compared to determine the effect of various stages of tissue disruption on the reversible and irreversible metabolism of the glucocorticoids. Oxidation of POH to PO was enhanced by homogenization of all the organs examined; further disruption by subcellular fractionation to microsomes reduced oxidation relative to homogenates but yielded values greater than the original minces. The reverse reaction, reduction of PO to POH, was also enhanced by homogenization, but microsomal preparations were less active than the minces. The irreversible elimination of the glucocorticoids was progressively diminished by disruption of normal architecture in all organs. Results of in vitro studies of glucocorticoid metabolism have provided discrepant results, as a function of the laboratory, the species, the organ and the organ preparation examined. These results provide insights into the source of discrepant results regarding steroid metabolism, as it appears that results of experimentation with glucocorticoid conversion and/or elimination may be a function of the method used. Additionally, the data support the hypothesis that the enzyme system involved in the interconversion of the glucocorticoids may not be a simple single protein which acts bidirectionally. PMID- 1620724 TI - Effects of calcium channel blockers on formalin-induced nociception and inflammation in rats. AB - The possible anti-inflammatory and antinociceptive effects of nitrendipine, nicardipine, diltiazem and verapamil were examined with formalin test in the rat paw. Pretreatment with these calcium channel blockers 1 h before formalin injection diminished formalin-induced inflammatory changes and nociceptive responses. Formalin-induced nociceptive responses were inhibited 20-90% by the calcium channel blockers. Nitrendipine and nicardipine were found to be highly effective in inhibiting the inflammatory changes, whereas the effects of verapamil and diltiazem were partial. Administration of naloxone affected neither the inflammatory changes and nociceptive responses induced by formalin nor the antiinflammatory and antinociceptive effects of the calcium channel blockers. The results suggest the possible anti-inflammatory and naloxone-insensitive antinociceptive properties of calcium channel blockers. PMID- 1620725 TI - Photobleaching of merocyanine 540: involvement of singlet molecular oxygen. AB - The purpose of this study was to assess the mechanism of merocyanine 540 (MC540) photobleaching in a liposomal system. Broad based visible irradiation of MC540 in unilamellar dilauroylphosphatidylcholine (DLPC) vesicles resulted in dye bleaching that was strictly O2 dependent. The rate of self-sensitized photobleaching was enhanced in D2O and inhibited by both azide and histidine, consistent with 1O2 intermediacy (Type II chemistry). Supportive evidence for this mechanism was obtained by using a Type II sensitizer, aluminum phthalocyanine tetrasulfonate (AlPcS lambda max = 678 nm). Irradiation of AlPcS and MC540 in DLPC with lambda greater than 630 nm (absorbed only by AlPcS) light resulted in rapid bleaching of MC540, which was stimulated by D2O and inhibited by azide. A rate constant of 10(7) M-1 s-1 was determined for the chemical quenching of 1O2 by MC540. The rate constant for physical quenching of 1O2 by MC540 was estimated to be ca 10(9) M-1 s-1. PMID- 1620726 TI - Photoacoustic detection of triplet state and singlet oxygen in highly absorbing samples. AB - A photoacoustic (PA) effect theory taking into account two heat sources corresponding to the radiationless relaxation processes of two states of different lifetimes and to the heat diffusion across the sample is herewith presented. Results obtained demonstrate that the amplitude and the phase of the PA signal depend on the sample's thermal properties, on its optical absorption coefficient, on the lifetime of the long-lived excited state, and on the ratio of the two heat sources. This ratio can be expressed as a function of the product of the energy of the excited state times the quantum yield of its production. Simulations of PA amplitude and phase variations vs light modulation frequency exhibit new features of the PA signal:phase inversion and fast decrease of the amplitude. Experimental verifications were carried out on solutions and gels. Fitting of the amplitude and phase variations allow us to measure the lifetime and conversion yield of the intermediate state which can be a triplet state or singlet oxygen, O2(1 delta g). The addition of an acceptor, specific to O2(1 delta g), induces changes in the amplitude of the PA signal which can be used to study the production and deactivation of this excited form of oxygen. This work demonstrates the usefulness of PA in the detection of metastable excited states such as the triplet state and singlet oxygen and in their quantitative analysis. PMID- 1620727 TI - Synthetic carotenoids, novel polyene polyketones and new capsorubin isomers as efficient quenchers of singlet molecular oxygen. AB - Novel synthetic polyene polyketones and new synthetic capsorubin isomers were examined for their ability to quench singlet molecular oxygen (1O2) generated by the thermodissociation of the endoperoxide of 3,3'-(1,4-naphthylene) dipropionate (NDPO2). C28-polyene-tetrone (1) exhibits the highest physical quenching rate constant with 1O2 (kq = 16 x 10(9) M-1 s-1). For comparison, the rate constant for the most efficient biological carotenoid, lycopene (3) is kq = 9 x 10(9) M-1 s-1 and that of beta-carotene (5) kq = 5 x 10(9) M-1 s-1. The presence of two oxalyl chromophores at the ends of the polyene chain seems to enhance the 1O2 quenching ability in the C28-polyene-tetrone (1). C28-polyene-tetrone-diacetal (2) (kq = 9 x 10(9) M-1 s-1) and C40-epiisocapsorubin (4) (kq = 8 x 10(9) M-1 s 1) also have high 1O2 quenching abilities. Two carotenoids from plants, phytoene and phytofluene, were much less efficient, kq values being below 10(7) M-1 s-1. Due to the very high singlet oxygen quenching abilities, C28-polyene-tetrone (1), C28-polyene-tetrone-diacetal (2) and C40-epiisocapsorubin (4) may have potential use in preventing 1O2-induced damage in biological and non-biological systems. PMID- 1620728 TI - In vivo spectrophotometric evaluation of neoplastic and non-neoplastic skin pigmented lesions. II: Discriminant analysis between nevus and melanoma. AB - Reflectance spectrophotometry from 420 to 780 nm on 31 primary melanoma and 31 benign nevi has been performed by using an external integrating sphere coupled to a spectrophotometer. Measurements show that reflectance spectra of melanoma and nevi manifest dissimilar patterns. From these spectra four variables, whose physical and/or physiological meanings remain to be investigated, have been derived. All of them are significantly different when compared between melanoma and nevi. A discriminant function between the two groups of lesions has been determined by using a stepwise discriminant analysis, resulting in a test with a sensitivity of 90.3% and a specificity of 77.4%. This method of discrimination between melanoma and nevi seems to have a discriminating power almost equal to that of a clinical judgement from a specialized medical doctor, thus suggesting a new method for screening skin pigmented lesions. PMID- 1620729 TI - Quenching of singlet oxygen by biomolecules from L1210 leukemia cells. AB - Singlet oxygen lifetimes for detergent-dispersed L1210 leukemia cells in deuterium oxide buffer were measured by following the decay of 1270 nm phosphorescence. Four photosensitizers and two detergents were studied. Stern Volmer plots were linear over the cell concentration range studied (0-10(7) cells/mL). The singlet-oxygen quenching constants obtained depended somewhat upon the specific combination of detergent and photosensitizer used. Extrapolation of the singlet-oxygen lifetime data to "100%" cell concentration (1.39 +/- 0.04 x 10(9) cells/mL) and correction for the contribution of the water solvent gave a singlet-oxygen lifetime between 0.17 and 0.32 microseconds for the L1210 leukemia cell. The theoretical contributions of various types of biological molecules within the L1210 cell to the total singlet-oxygen quenching were calculated from their concentrations and their quenching constants. These calculations suggest that proteins will quench most of the singlet-oxygen. Only about 7% of the singlet-oxygen is quenched by water. PMID- 1620731 TI - Wavelength dependence (150-290 nm) of the formation of the cyclobutane dimer and the (6-4) photoproduct of thymine. AB - The action cross sections for the formation of the cyclobutane dimer and the (6 4) photoproduct of thymine as well as the absorption cross sections of thymine were determined in the wavelength region between 150 and 290 nm. Thymine films sublimed on glass plates were irradiated by monochromatic photons in a vacuum; the induced photoproducts were quantitatively analyzed by high-performance liquid chromatography (HPLC). Under our conditions, two major peaks appeared on the HPLC chromatograms of irradiated samples. The two peaks were identified as being the cis-syn cyclobutane dimer and the (6-4) photoproduct, based on their HPLC retention times, absorption spectra in the effluent, and photochemical reactivity. The fractions of the two photoproducts increased linearly with the fluence at low fluences over the entire wavelength range. Their action cross sections were determined by the slopes of the linear fluence response curve at 10 nm intervals between 150 and 290 nm. The two action spectra showed a similar wavelength dependence and had a maximum at 270 nm as well as two minor peaks at 180 and 220 nm, at which wavelengths the peaks of the absorption spectrum of thymine sublimed on a CaF2 crystal plate appeared. The quantum yields had relatively constant values of around 0.008 for the dimer and 0.013 for the (6-4) photoproduct above 200 nm, decreasing to 0.003 and 0.006, respectively, at 150 nm as the wavelength became shorter. PMID- 1620730 TI - The photobiological activity of 5-geranoxypsoralen and its photoproducts. AB - 5-geranoxypsoralen (Bergamottin) does not photosensitize bacteria or a bacterial virus. It does, however, photosensitize mammalian cells in tissue culture. Irradiation with either black light (300-400 nm) or fluorescent ceiling lights produced at least four photobiologically active degradation products, the chemical nature of which still remains to be elucidated. Prolonged exposure to black light resulted in the formation of inactive molecule(s). PMID- 1620732 TI - Multiple modality treatment of carcinoma cells with Pt(Rh-123)2 plus x-ray plus light. AB - A complex of platinum tetrachloride with two molecules of rhodamine-123 (Rh-123), Pt(Rh-123)2, has been reported to act as hypoxic cell radiosensitizer of carcinoma cells in vitro and in vivo. In the present paper we report that Pt(Rh 123)2 photosensitizes human mammary carcinoma (MCF-7) cells and cis-platinum resistant human mammary carcinoma (MCF-7/CP) cells to 400-800 nm light in vitro. The efficiency of photosensitization by Pt(Rh-123)2 was 10 times greater than for Rh-123. Combination therapy using Pt(Rh-123)2 plus x-ray plus light was also much more effective compared to the combination therapy using Rh-123 plus x-ray plus light. After 15 microM of Rh-123 plus x-ray (0-8 Gy) plus light (5 J/cm2) treatment, cell survival curve was parallel to the x-ray cell survival curve with an initial decrease in the surviving fraction corresponding to the drug plus light mediated killing. Cell killing caused by Rh-123 (15 microM) plus x-ray (0-8 Gy) plus light (5 J/cm2) was additive as determined by the product of the surviving fraction after Rh-123 plus light and x-ray. In contrast, for 15 microM of Pt(Rh-123)2 plus x-ray (8 Gy) plus light (5 J/cm2) treatment, whereas additive killing predicts a survival fraction of approximately 0.024, in reality, the combination therapy caused the survival fraction to decrease to 0.0012, implying that the cell killing was enhanced by a factor of 20. Using Pt(Rh-123)2 plus x ray plus light, supra-additive cell killing was also observed under hypoxic conditions, although compared to normally oxygenated conditions the degree of cytotoxicity was significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620733 TI - Photoaging effects on spectral transmittance of plastic filters. AB - We examined the effects of ultraviolet (UV) radiation in combination with high levels of infrared (IR) radiation on the spectral transmittance of plastic filters. The biological action spectrum for damage to the human eye and skin changes dramatically in the 300-400 nm wavelength range. Cut-off filters used in this region to shape the spectrum of exposure sources are thus critical to the design of experiments which use broadband light sources. The changes in transmittance of three types of plastic filters were observed over an exposure period of 1000 h. One set of three filters was exposed mainly to UV radiation, while the other set was exposed to UV radiation plus IR radiation. Filters exposed to both UV and IR radiation showed spectral changes in their transmittance, while the filters exposed to UV only showed no measurable changes. PMID- 1620734 TI - Comparative pharmacological investigations of Allium ursinum and Allium sativum. AB - Extracts of wild garlic (Allium ursinum) and garlic (A. sativum) with defined chemical compositions were investigated for their in vitro inhibitory potential on 5-lipoxygenase (LO), cyclooxygenase (CO), thrombocyte aggregation (TA), and angiotensin I-converting enzyme (ACE). The inhibition rates as IC50 values of both extracts for 5-LO, CO, and TA showed a good correlation with the %-content of the major S-containing compounds (thiosulfinates and ajoenes) of the various extracts. In the 5-LO and CO test the garlic extracts are slightly superior to the wild garlic extracts whereas, in the TA test, no differences could be found. In the ACE test the water extract of the leaves of wild garlic containing glutamyl-peptides showed the highest inhibitory activity followed by that of the garlic leaf and the bulbs of both drugs. The comparative studies underline the usefulness of wild garlic as a substitute of garlic. PMID- 1620735 TI - Antibacterial diterpenes from the aerial parts of Premna oligotricha. PMID- 1620736 TI - Alkaloids of Thalictrum glandulosissimum. PMID- 1620737 TI - Pharmacologically active phenylpropanoids from Senra incana. AB - Coniferaldehyde, scopoletin, sinapaldehyde, and syringaldehyde were isolated from an aqueous extract of Senra incana. All four compounds inhibited prostaglandin synthetase in a dose-dependent way. Compared to aspirin, the potency of coniferaldehyde and scopoletin was about five times higher, whereas syringaldehyde and sinapaldehyde had about half the potency of this reference compound. On topical application, sinapaldehyde and scopoletin dose-dependently inhibited ethyl phenylpropiolate-induced edema of the rat ear. The active dose range was 1-10 micrograms/ear. Higher doses had a lower effect. Syringaldehyde was active in the range 20-100 micrograms/ear, whereas the effect of coniferaldehyde was inconclusive. Coniferaldehyde and sinapaldehyde inhibited electrically induced contractions of the guinea pig ileum in a dose-dependent way. Syringaldehyde showed a weak inhibition at a concentration of 550 microM. PMID- 1620738 TI - Antispasmodic activity of beta-damascenone and E-phytol isolated from Ipomoea pes caprae. AB - The crude extract (IPA) of the plant Ipomoea pes-caprae (L.) R. Br. has previously been shown to antagonize smooth muscle contractions induced by several agonists via a non-specific mechanism. Bioassay-guided fractionation of IPA resulted in isolation of the antispasmodically acting isoprenoids beta damascenone and E-phytol. Their antispasmodic potencies were found to be in the same range as that of papaverine, a general spasmolytic agent. This effect was suggested to play a role in the previously observed anti-inflammatory activity of IPA by interfering with the contraction of endothelial cells. Severe vascular contraction has been shown to be involved in the dermatitis caused by toxic jellyfishes. It is possible that beta-damascenone and E-phytol, by interfering with the contraction of vascular smooth muscle cells, are partly responsible for the previously reported effectiveness of IPA in the treatment of such dermatitis. PMID- 1620739 TI - An evaluation of Lawsonia alba extract as hepatoprotective agent. AB - The hepatoprotective activity of an ethanol-water (1:1) extract of Lawsonia alba has been studied against CCl4-induced liver toxicity. The effects of the extract on hexobarbitone-induced sleep, BSP clearance, and on certain biochemical parameters indicated its protective role. There was no effect on bile flow. The extract did not show any signs of toxicity and the minimum lethal dose was greater than 2.0 g/kg p.o. in mice. PMID- 1620740 TI - The effect of N-deacetylcolchiceine on serum lipoproteins in rats. AB - N-Deacetylcolchiceine (DAC) administered i.p. to rats decreased the level of serum cholesterol and apoB. It was accompanied by the fall of HDL-C due to the decrease of both HDL subfractions HDLa and HDLb, and by a rather weaker decrease of LDL-C. The levels of serum and lipoprotein triacylglycerols were not significantly affected. The "clearing reaction" to heparin in DAC rats differed from controls with regard to plasma cholesterol resulting in its accumulation in HDLa and LDL simultaneously with an increased activity of post-heparin lipoprotein lipase. These results suggest that the DAC accelerates the lipoprotein cholesterol metabolism. PMID- 1620741 TI - Antitumor activity of cell wall beta-1,3/1,6-glucans from Phytophthora species. AB - From the cell walls of various Phytophthora species (Oomycetes) different water soluble beta-1,3/1,6-glucans were isolated and characterized. The glucans with relative molecular masses between 13 and 50 kd exhibited varying degrees of branching in the beta-1,3-linked glucan backbone ranging from 14 to 50%. The dose dependent antitumor activity of the glucans against allogeneic sarcoma-180 was investigated. It could be demonstrated that beta-1,3/1,6-glucans with relative molecular masses below 50 kd can exhibit a prominent antitumor activity (inhibition rate up to 99%), being comparable to that of the high relative molecular mass (450 kd) beta-1,3/1,6-glucans. Biological activity of the glucans could be shown to be correlated with a low degree of branching. The most potent glucan with a degree of branching of 14% also was active against the syngeneic DBA/2-MC.SC-1 fibrosarcoma (inhibition rate up to 90%) and in combination with a suboptimum dose of diethylstilbestrol against Nobel-Nb prostate carcinoma (inhibition rate up to 90%). PMID- 1620742 TI - Indole alkaloids with in vitro antiproliferative activity from the ammoniacal extract of Nauclea orientalis. AB - Nine angustine-type alkaloids were isolated from ammoniacal extracts of Nauclea orientalis L. (Rubiaceae). Three of them, 10-hydroxyangustine and the two diastereoisomeric 3,14-dihydroangustolines, have not been described in the literature thus far. The structures of the isolates were determined with spectroscopic methods, mainly 1D- and 2D-NMR spectroscopy. The compounds were found to exhibit in vitro anti-proliferative activity against the human bladder carcinoma T-24 cell line and against EGF (epidermal growth factor)-dependent mouse epidermal keratinocytes. By using overpressure layer chromatography, it was shown that minor quantities of these alkaloids occur in dried Nauclea orientalis leaves. The use of ammonia in the extraction process results in a significant increase in the formation of angustine-type alkaloids from strictosamide-type precursors. PMID- 1620743 TI - On the influence of the sugar moiety on the antigonadotropic activity of luteoline glycosides. AB - Luteolin-7-glucoside and luteolin-7-glucuronide were isolated from Lycopus europaeus L. (Lamiaceae) and identified by 1H- and 13C-NMR spectroscopy. Luteolin 7-glucuronide proved to be active against PMSG in vitro as well as in vivo, whereas the other flavone glycosides occurring in the plant were completely inactive. PMID- 1620744 TI - Molluscicidal constituents of Calophyllum from Madagascar: activity of some natural and synthetic neoflavonoids and khellactones. AB - Crude extracts of seeds, leaves and barks of four Madagascan Calophyllum species: C. inophyllum, C. recedens, C. chapelieri, and C. verticullatum, have been tested for molluscicidal activity against Biomphalaria glabrata. All seed extracts showed significant activity. The major constituents of the most active Calophyllum species were examined. Some related coumarinic derivatives were synthesized in order to improve the biological activity. Among the compounds prepared, 5,7-dihydroxy-6-(2-methylbutyryl)-4-phenyl-coumarin presented an interesting molluscicidal activity. PMID- 1620745 TI - Tyromycin A: a novel inhibitor of leucine and cysteine aminopeptidases from Tyromyces lacteus. AB - Tyromycin A, a new inhibitor of leucine and cysteine aminopeptidases has been isolated from mycelial cultures of the basidiomycete Tyromyces lacteus (Fr.) Murr. Its structure was established as 1,16-bis-[4-methyl-2,5-dioxo-3 furyl]hexadecane (1) by spectral analysis and transformation into ester and imide derivatives. PMID- 1620746 TI - Chemical structure and biological activity of polysaccharides from Hibiscus sabdariffa. AB - Three water-soluble polysaccharides have been isolated from flower buds of Hibiscus sabdariffa L. (HIB 1,2,3). The neutral polysaccharides (HIB 1 and 2) are composed of arabinans and arabinogalactans of low relative molecular mass. The major fraction was investigated by methylation analysis, pectinase-treatment, mild acid hydrolysis and NMR studies, and it was shown to be a pectin-like molecule (Mr = 10(5)d). The main chain is composed of alpha-1,4-linked GalA (24% methyl-esterified) and alpha-1,2-linked Rha. Side chains are built of Gal and Ara and are connected to the main chain via C-4 of every third Rha. Its structure seems to be different from polysaccharide structures described in other species of the Hibiscus genus and the Malvaceae family. All fractions were assayed for possible immune-modulating effects. All fractions showed some activity, but the main acidic fraction was contaminated with lipopolysaccharide, and therefore its shown activity has to be discussed carefully. PMID- 1620747 TI - Monoclonal antibody-based enzyme immunoassay for the quantitative determination of the tropane alkaloid, scopolamine. AB - A monoclonal antibody (SP1-4-A2) against scopolamine was produced, characterized, and used to develop a sensitive and selective, competitive enzyme immunoassay for the quantitation of the alkaloid. The assay uses nor-scopolamine-N-beta-propionic acid coupled to alkaline phosphatase as tracer and is linear from 10 pg to 10 ng of scopolamine. As little as 10 pg of scopolamine can be quantitated in an unprocessed plant extract or in human serum after suitable dilution, corresponding to detection limits of 0.1 ng scopolamine/ml of plant extract or 0.5 ng/ml of serum. The assay is more selective for scopolamine (percent cross reactions for hyoscyamine = 0.21%, 6-hydroxy-hyoscyamine = 0.17%) than previously reported immunoassays. The assay format was designed to minimize intra- and inter plate variabilities which are, on an average, all below 3% (coefficients of variation). The assay reported here has been validated against an HPLC-based technique using plant samples and was shown to correlate closely (y = 0.959 x + 0.14, r = 0.982). PMID- 1620748 TI - Pharmacokinetics of vinyldithiins, transformation products of allicin. AB - The pharmacokinetic behaviour of vinyldithiins, the main constituents of oily preparations of garlic (Allium sativum L.), was investigated after oral administration of 27 mg 2-vinyl-4H-1,3-dithiin and 9 mg 3-vinyl-4H-1,2-dithiin to rats. In serum, kidney, and fat tissue, both vinyldithiins could be detected by GC-MS over a period of 24 h, whereas in liver only 1,3-vinyldithiin was found. Pharmacokinetic parameters (t1/2, ke, Cltot, AUC, and Vd) were determined using compartment models, elucidating the different pharmacokinetic behaviour of both vinyldithiins. 1,3-Vinyldithiin seems to be less lipophilic and is rapidly eliminated from serum, kidney, and fat tissue, whereas 1,2-vinyldithiin is more lipophilic and shows a tendency to accumulate in fat tissue. Experiments with liver homogenate confirmed the in vivo findings on the different degradation rates of both vinyldithiins. Allicin, the precursor of the vinyldithiins, is metabolized more rapidly in liver homogenate than the vinyldithiins. PMID- 1620749 TI - [Isolation and structure elucidation of further new saponins from Solidago canadensis]. AB - Four new main saponins (canadensis-saponins 5-8) (compounds 5-8) were isolated from Solidago canadensis L. (Asteraceae). Using GC/MS, FAB-MS, and mainly 2D-NMR techniques their structures were identified as 3-O-[beta-D-glucopyranosyl(1----3) beta-D- glucopyranosyl]-28-O-[beta-D-galactopyranosyl(1----2)-alpha-L- rhamnopyranosyl-(1----3)-beta-D-xylopyranosyl-(1----4)-[beta-D- xylopyranosyl-(1- --3)]-alpha-L-rhamnopyranosyl-(1----2)-[beta-D-apio -D- furanosyl-(1----3)]-beta D-6-deoxyglucopyranosyl-(1----)]-bayog enin(5),3-O- [beta-D-glucopyranosyl-(1--- 3)-beta-D-glucopyranosyl]-28-O-[beta-D- galactopyranosyl-(1----2)-alpha-L rhamnopyranosyl-(1----3)-beta-D- xylopyranosyl-(1----4)-[beta-D-xylopyranosyl-(1- --3)]-alpha-L- rhamnopyranosyl-(1----2)-[beta-D-apio-D-furanosyl-(1----3)]- arabinopyranosyl-(1----)]bayogenin(6),3-O-[beta-D-glucopy ran osyl-(1----3)- beta D-glucopyranosyl]-28-O-[beta-D-galactopyranosyl-(1----2)- alpha-L-rhamnopyranosyl (1----3)-beta-D-xylopyranosyl-(1----4)-[beta-D- xylopyranosyl-(1----3)]-alpha-L rhamnopyranosyl-(1----2)-[alpha-L- rhamnopyranosyl-(1----3)]-beta-D-6 deoxyglucopyranosyl-(1----)]-++ +bayogenin (7), and 3-O-[beta-D-glucopyranosyl-(1 ---3)-beta-D-glucopyranosyl]-28-[O- beta-D-galactopyranosyl-(1----2)-alpha-L rhamnopyranosyl-(1----3)-beta-D - xylopyranosyl-(1----4)-[beta-D-xylopyranosyl-(1 ---3)]-alpha-L- rhamnopyranosyl-(1----2)-[alpha-L-rhamnopyranosyl-(1--- 3)]arabinopyr anosyl - (1----)[-bayogenin (8). PMID- 1620750 TI - Two new saponins from the roots of Phytolacca esculenta. AB - Two triterpenoidal saponins having phytolaccagenin as the aglycone were isolated from the roots of Phytolacca esculenta (Phytolaccaceae). The structures of two new saponins, esculentoside I and esculentoside N, were established to be 3-O [beta-D-glucopyranosyl-(1----4)-beta-D- glucopyranosyl]-28-O-beta-D glucopyranosyl-phytolaccagenin and 3-O-[beta-D-glucopyranosyl(1----4)-beta-D xylopyranosyl(1----4)-beta-D- glucopyranosyl]-28-O-beta-D glucopyranosylphytolaccagenin, respectively, on the basis of spectroscopic and chemical evidence. PMID- 1620752 TI - A modified Regressive Coping Checklist: some Australian data. AB - The Regressive Coping Checklist has been used to measure the extent to which individuals cope with stress by denying, minimizing, or avoiding stressful situations. In this study, the checklist was modified to include the frequency of use of regressive coping strategies and was shown to be a moderately reliable instrument (alpha = .57) when used with a sample of 750 Australian postprimary teachers. PMID- 1620751 TI - A diagnostic analysis of the Casebooks of Ticehurst House Asylum, 1845-1890. AB - Ticehurst House, a private asylum, flourished during the nineteenth century as the most expensive of such establishments, being owned and run by the Drs Newington over five successive generations. The discovery of the full set of patient casebooks begun in 1845-6 made it possible to review in detail the clinical features of a complete cohort of patients admitted to the asylum between 1845 and 1890. Six-hundred-and-one patients were thus analysed in terms of their age, sex, length of stay, symptoms, treatment and outcome. Modern operational diagnoses were used, and 80% of the cohort were found to conform to Research Diagnostic Criteria, in particular to the categories for schizophrenia and manic depressive disorder. An additional finding was the high prevalence of movement and postural disorder among the schizophrenic group, as well as a significant trend towards the selection of a treatable, good-outcome group of patients with manic-depressive illness. These results are discussed by comparison with other modern studies of the asylum period, and in the contemporary context of Victorian psychological medicine. It is suggested that the violence, physicality and chronicity of psychotic illness must be seen as central to the debate about the rise of the asylum in nineteenth-century Britain. Furthermore, the similarity in core symptoms found in such patients and those seen in the 1980s indicates that the categories 'schizophrenia' and 'manic-depressive disorder' have a robust validity that is not confined to the social parameters of a particular time period. PMID- 1620753 TI - Testing Gibbs and Martin's theory of suicide. AB - Over 32 nations, status integration correlated more strongly with suicide rates than two other social variables. Over 30 states of the United States of America, status integration performed worse than the percent born out-of-state and better than the divorce rates. PMID- 1620754 TI - Psychological attributes of young adult smokers. AB - To study the psychological aspects of cigarette-smoking in community adults, we examined longitudinal data from a sample of young people (from age 15 to 23 years). Questions on smoking behavior had been asked during the last five years of the study, and information on self-esteem, depressive affect, negative mood, hopelessness, psychological disturbance, locus of control, social alienation and health was also available. Current smokers in the last year of the study had differed from nonsmokers nine years previously by having more external locus of control and now were less likely to report their health as excellent. Most smokers also drank alcohol, but cigarette consumption did not differ for drinkers and nondrinkers. Contrary to expectations, current smokers showed no distinctive psychological attributes, and those who started or stopped smoking were similarly undistinctive in psychological terms. Results suggest that efforts to stress the self-destructive or antisocial nature of tobacco use have not been accepted by the smokers in this age group (M = 23.6 yr.). PMID- 1620755 TI - Personality profile of conference-going clergy in England. AB - The Eysenck Personality Questionnaire was completed by 40 male clergy attending a residential conference in England. The data suggest that conference-going clergy are more extraverted than clergy in general. PMID- 1620756 TI - Relationship between boredom proneness and impulsivity. AB - As part of a larger investigation, the relationship between boredom proneness and impulsiveness was investigated among 381 undergraduates. A significant positive correlation of .56 obtained between boredom proneness and impulsivity. Significant positive associations were also found between scores on boredom proneness and impulsiveness subscales. PMID- 1620757 TI - The Rotter I-E scale as a predictor of relapse in a population of compulsive gamblers. AB - Profile surveys, completed Rotter I-E scales, and questionnaires on past relapse behavior were collected from 108 New Jersey compulsive gamblers who attended Gamblers Anonymous, and an attempt was made, based on the findings, to predict incidence of compulsive gamblers' relapse. Relationships between I-E scores and extent of relapse-free periods, and I-E scores and relapse, with the variables of religious background, age, marital status, education, type of work, and childhood physical abuse were investigated. In every instance the relationship found was statistically non-significant. PMID- 1620758 TI - Changes in learning-style preferences: comments on Geiger and Pinto. AB - Geiger and Pinto reached unwarranted conclusions regarding changes in learning style preferences over a two-year period. Problems with the instrument and data analysis require a revision of their conclusions. PMID- 1620759 TI - Reply to Duryea. PMID- 1620760 TI - Influence of involuntary migration on children's perception of control. AB - The present study was done to explore the influence of involuntary migration on children's perception of control. Three groups of 50 black South African children each were randomly selected from three types of migrant populations. A control group of 50 nonmigrant children was also formed. To this sample a multidimensional measure of children's perception of control was administered. Analysis showed differences in perception of control by migrant and nonmigrant children as well as among the various groups of migrant children. Such variations were attributed to migration process and differences in educational and socioeconomic status. PMID- 1620761 TI - Development and application of a writing attitude survey for grades 1 to 3. AB - The purpose of these studies was to develop and use a writing attitude survey for students in Grades 1 to 3 modeled after the survey developed and used with students in Grades 4 to 8 in 1991. A 19-item survey was administered to 394 children in Grades 1, 2, and 3. The instrument was then used in an experiment to assess the effect of instructional treatment, grade, and participation on 112 students' attitudes toward writing. There were no significant main effects for treatment or for time of measurement. There were no significant interactions, but there was a significant main effect for grade. Follow-up of significant main effects using Tukey tests indicated that 52 third graders had significantly more positive attitudes toward writing than 60 fifth graders. PMID- 1620762 TI - Culture, environment: value judgments about cognitive development. AB - Cross-cultural studies have suggested cultural and environmental influences in cognitive development. Such differences have been described as value free and do not imply that one group is better than another. In this paper such a stance is challenged as unrealistic. PMID- 1620763 TI - Longitudinal survey of anxiety and depression in drug users and addicts. AB - As a follow-up to our 1990 study of anxiety and depression among drug users, after two years 44 men differed in their experience with drugs and from the first phase of the study five of the 20 controls became drug users, two of the 20 drug users became addicts, and one of the 20 drug abusers died from AIDS. These findings do not confirm the 1989 thesis of Newcomb and Bentler on the etiology of addiction, that depression and anxiety imply greater drug use. Positive correlations were found for drug use with anxiety and depression. Such data confirm those found by De Moja in 1990. PMID- 1620765 TI - Hispanic-American MMPI research (1949-1992): a comprehensive bibliography. AB - The purpose of this article is twofold. The first is to outline key events in the history of Hispanic MMPI research. Since 1949, researchers have documented the MMPI performance of Hispanic-Americans in a variety of clinical and nonclinical settings. The second purpose is to present a comprehensive bibliography of Hispanic MMPI research by research setting. A total of 86 studies are listed in this bibliography. PMID- 1620764 TI - Correlations between scores on a continuous performance test and parents' ratings of attention problems and impulsivity in children. AB - This is a study of the relationship between a continuous performance test and parents' behavioral ratings of attention problems and impulsivity in 45 boys who had been referred to a clinic for learning and behavioral problems. No significant correlations obtained between these two methods of assessment. Perhaps the lack of congruence is due to the multidimensional nature of both attention problems and impulsivity. Suggestions for clinical practice and further research are discussed. PMID- 1620766 TI - Humor in counseling and psychotherapy: a 20-year retrospective. AB - This article briefly annotates the development of research and theorizing on the use of humor in psychotherapy. Beginning in 1970 and continuing through 1990, the main literature was cursorily scanned. A total of 67 sources are offered for bibliographic use. Sadly, tangential forms of humor such as fun, mirth, frivolity, songs, jokes, puns, witticisms, and other forms of humor are not as readily addressed or investigated. PMID- 1620767 TI - Personality factors in Psy.D. students: empirically derived comparisons between men and women. AB - A total of 180 students in a Doctor of Psychology program of an APA-accredited Professional School of Psychology (55 men and 125 women) took the MMPI for course requirements. A larger subgroup (43 men and 88 women) also completed the Adjective Check List. Men scored higher than women on the MMPI dimensions of Assertion (Pd), Organization (Pt), and Imagination (Sc). Women scored higher on the Ego Strength Scale (Es). Men scored higher on the Check List scale of Dominance. Data were compared with a previous report of MMPIs of Ph.D. students, and few differences were observed. Findings were discussed in terms of stereotypical role behaviors from which doctoral students are not yet immune. PMID- 1620768 TI - Sources of bias in perception of HIV risk by injecting drug-users. AB - The role of bias in assessments of personal susceptibility to threat is a central concept in research on perception of risk. The current study aimed to clarify the association between perceived personal susceptibility to infection with HIV/AIDS and injecting risk behaviour with injecting drug-users' perception of the baseline rate of infection with HIV/AIDS. 1262 injecting drug-users from Australian cities were interviewed. The injecting drug-users were divided into high- and low-risk groups depending on the HIV/AIDS risk associated with their injecting behaviour. Subjects were subdivided into low-, medium-, and high perceived personal susceptibility groups. Analysis indicated that injecting drug users in the high-risk group underestimated the prevalence of HIV/AIDS infection relative to those in the low-risk group and that perceived personal susceptibility was rationally related to estimates of the baseline rate of infection. PMID- 1620769 TI - Investigating the relationship between the Millon Adolescent Personality Inventory and the Personality Inventory for Children with a sample of learning disabled adolescents. AB - The present study involved a preliminary evaluation of the correlations between subscales on the Personality Inventory for Children and the Millon Adolescent Personality Inventory with 25 learning disabled adolescents. Analysis yielded a number of significant correlations between these two scales, using the Personality Inventory for Children as the anchor scale, and showed that these adolescents as a group scored within clinically acceptable ranges on both diagnostic scales. Both scales need further psychometric and clinical investigation, and as such, the limitations of the study and the research needed are addressed, including the need for more multitrait, multimethod studies. PMID- 1620770 TI - Correlation between rates of rape and abortion. AB - To test the argument made by abortion advocates that increases in unwanted pregnancies that are due to rape justify the need for legal abortions, a Pearson correlation was calculated between the forcible rape rates and the legal abortion rates in the USA for 1985. The calculation gave an r of .21, a nonsignificant value. PMID- 1620771 TI - When is couples therapy necessary and sufficient? AB - Couples therapy is not a unified form of treatment but draws on a heterogeneous range of influencing processes. When distressed couples are relatively stable and interested in effecting a harmonious modus vivendi, didactic training will usually achieve salubrious outcomes. When individual agendas, hidden or otherwise, undermine the relationship, individual therapy is often essential before the couple can benefit from conjoint therapy. Those who insist on working only within dyadic, triadic, or family contexts may fail to achieve desirable goals. PMID- 1620772 TI - Prediction of endocrine stress reactions by means of personality variables. AB - The study examined the predictability of endocrine stress indicators on the basis of personality measures. The subjects were 83 computer operators (63 men, 20 women; mean age 28 years) who by means of an experimental situation were confronted with a mild stressor (a cognitive two-channel task with a high information load). Using scores on personality questionnaires (comprising scales for defense mechanisms, neuroticism, and 2 achievement motivation variables), subjects were classified into extreme groups of stress-resistant (17 subjects) versus nonstress-resistant (13 subjects). Immediately after the experiment blood samples were taken to assay the norepinephrine metabolites plasma-free 3-methoxy 4-hydroxy-phenylglycol (MHPG) and MHPG sulfate (MHPG.SO4), which formed the dependent variables. Personality measures and endocrine stress indicators were until the final analysis of the data kept apart by a double-blind strategy. A significant difference was noted in the MHPG level between the stress-resistant and the nonstress-resistant group. The value and applicability of these results for stress prevention is discussed. PMID- 1620773 TI - Prescribing therapy for depression: the role of learned resourcefulness, a failure to replicate. AB - Work in 1985 by Simons, Lustman, Wetzel, and Murphy showed that a patient's score on Rosenbaum's self-control scale predicted differential response to treatments for depression, with a high score predicting a good outcome with talking therapy and a low score a good outcome with drug therapy. This study of 37 patients did not replicate those findings. Using the same paradigm, we predicted response correctly 7 times and incorrectly 16 times, a clear failure. A valid method for choosing the best treatment for a patient with major depression remains to be found. PMID- 1620774 TI - Neurolinguistic programming training, trait anxiety, and locus of control. AB - Training in the neurolinguistic programming techniques of shifting perceptual position, visual-kinesthetic dissociation, timelines, and change-history, all based on experiential cognitive processing of remembered events, leads to an increased awareness of behavioral contingencies and a more sensitive recognition of environmental cues which could serve to lower trait anxiety and increase the sense of internal control. This study reports on within-person and between-group changes in trait anxiety and locus of control as measured on the Spielberger State-Trait Anxiety Inventory and Wallston, Wallston, and DeVallis' Multiple Health Locus of Control immediately following a 21-day residential training in neurolinguistic programming. Significant with-in-person decreases in trait anxiety scores and increases in internal locus of control scores were observed as predicted. Chance and powerful other locus of control scores were unchanged. Significant differences were noted on trait anxiety and locus of control scores between European and U.S. participants, although change scores were similar for the two groups. These findings are consistent with the hypothesis that this training may lower trait-anxiety scores and increase internal locus of control scores. A matched control group was not available, and follow-up was unfortunately not possible. PMID- 1620775 TI - Another look at the aptitude-achievement distinction. AB - 48 high school students were administered the Arithmetic subtest of the Wechsler Adult Intelligence Scale--Revised, the Mathematics subtest of the Peabody Individual Achievement Test--Revised, and the Stanford Diagnostic Mathematics Test. Correlations, of about .80 among the three tests, were interpreted as supporting a part of the continuum theory of Humphreys, Anastasi, and Cronbach for conceptualizing the distinction between aptitude and achievement tests. PMID- 1620776 TI - Personality disorder concept scales and 16 PF dimensions. AB - Using 148 clients from a private practice sample, concurrent scores on the Morey, Waugh, and Blashfield Minnesota Multiphasic Personality Inventory Scales and the Sixteen Personality Factor Questionnaire were factor analyzed in an attempt to map the Axis II disorders within a circumplex of interpersonal behavior. Individual predictions about the 16 PF primaries were made and then equations were developed to predict the Morey, Waugh, Blashfield MMPI scales from the 16 PF scores. Using a separate sample of 43 clients and 21 students, a cross-validation of concepts was performed by using the 16 PF to generate the MMPI scores and correlating the predicted scores with concurrent Millon Clinical Multiaxial Inventory scores. Concordance of the personality disorder characterizations across the instruments was high. Many of the predicted personality disorder characteristics were supported by the research, and 10 of 11 correlations with the Millon were significant. This research suggests the 16 PF is useful for generating hypotheses about personality disorders and that the Axis II conceptualizations fit as expected within normal personality space. PMID- 1620777 TI - Relationships among hope, psychosocial development, and locus of control. AB - 29 male and 79 female undergraduate and graduate students took the 1986 Miller Hope Scale, Beck's 1988 Hopelessness Scale, Erikson's Psychosocial Stage Inventory, Levenson's 1972 Locus of Control Scale and rated their present state of hopefulness on a 10-point scale. As expected, scores on both the Miller Hope Scale and the self-rated hope scale were negatively correlated with scores on Beck's Hopelessness Scale, but positively with scores on Erikson's Psychosocial Stage Inventory. Thus, greater hopelessness was associated with more successful resolution of psychosocial issues. The Miller Hope Scale was negatively and Beck's Hopelessness Scale was positively associated on the Locus of Control Scale with viewing control as from powerful others or chance. Therefore, lack of hopefulness was related with the perception that external factors control one's life. The Miller Hope Scale and scores on self-rated hopefulness were not significantly correlated. The concept of hope is more complex than currently measured by any single scale and requires further refinement. PMID- 1620778 TI - Academic and nonacademic self-concepts: influence of recent life-change experiences and demographic, social, and health variables. AB - For 150 undergraduate students (50 men, 100 women) the influences of demographic, social, health, and recent life-change experiences were examined on four facets of academic self-concept and nine facets of nonacademic self-concept. Multiple regression analyses showed that, in general, past academic performance, family structure, and family satisfaction were important predictors of academic self concept. Family structure, family satisfaction, social satisfaction, mental stress associated with recent life-change experiences, and health factors in general were important predictors of nonacademic self-concept. Recent life-change experiences and mental health were significantly associated, more prominently among subjects who were low on emotional self-concept than those who scored high. PMID- 1620779 TI - Subtest scatter is not an indicator of inaccuracy for short-form estimates of IQ. AB - The range of scaled scores does not provide information about the inaccuracy of estimates of IQ based on short forms of the test. Subtest scatter on a short form of an intelligence test may justify the complete administration for elaborative or clinical reasons. The criteria for reliable and abnormal ranges of scores for estimates based on short forms are calculable and should be examined to evaluate their usefulness. PMID- 1620780 TI - Geophysical variables and behavior: LXX. Testing electromagnetic explanations for a possible psychokinetic effect of therapeutic touch on germinating corn seed. AB - Designs used to test claims for psychic healing of living systems not amenable to suggestion may produce artifact in the results when there is failure to control for other possible explanations. Some experimental methods in psychokinesis may produce electromagnetic field flux which could lead to erroneous conclusions. This study adds electrical and magnetic controls to assess their effect, leading to the conclusion that therapeutically touched corn seeds did not recover from saline injury significantly better than untreated controls. PMID- 1620781 TI - Conditional stimulus control of childrens' sequence production. AB - Normally capable children were first taught to touch in sequence each of a set of five physically dissimilar stimuli (Sequence A). Another set of stimuli was then used to train sequence B. Next, direct training established conditional control of the production of the A sequence and its reversal: in the presence of one printed word, touching the stimuli in the order A1----A2----A3----A4----A5 was reinforced; in the presence of another word, touching the stimuli in the order A5 ---A4----A3----A2----A1 was reinforced. During probe sessions, the printed words also exercised conditional control over production of the B sequence and its reversal for five of six subjects, suggesting the formation of stimulus classes. Four of these five subjects also performed mixed sequences under conditional control of the words (e.g., A1----B2----A3----B4----A5 and its reversal), verifying that the stimuli which occupied the same position in each sequence were members of the same class. PMID- 1620782 TI - Prevalence of undetected alcohol dependence in the mental health diagnostic interview. AB - The prevalence of undetected alcohol dependence was examined utilizing the Michigan Alcohol Screening Test for 118 (68 women) users of community mental health services as part of a Quality Assurance Review. Clinicians did not uniformly request information about substance abuse in the diagnostic interview and did not uniformly address alcohol abuse in the treatment plan when alcohol dependence was diagnosed. Other programs may have similar problems. PMID- 1620783 TI - Beyond FIRO-B--three new theory-derived measures--Element B: behavior, Element F: feelings, Element S: self. AB - Although the FIRO-B instrument has been used widely for a large number of purposes, it was not designed as a general purpose instrument. Several years ago, after revising the FIRO theory underlying the instrument based on over 20 years' experience with the instrument and related activities, the author revised the FIRO-B extensively, so extensively it was given a new name, Element B. The new instrument is much stronger both theoretically and psychometrically while at the same time retaining the simplicity and shortness of the original. In addition, two new instruments based on the same theory were designed, developed, and tested. They measure feelings (Element F) and self-concept (Element S). All three instruments have, over the past 10 years, been used primarily as training instruments. When given in conjunction with other methods, they have been used for improving self-awareness, teamwork, morale, and productivity in such organizations as Procter & Gamble, AT&T, NASA, Amdahl Corporation, the Swedish Army, and about 100 companies in Japan. Included is a comment on scales anchored both logically, using methods such as facet design and unidimensional scaling, and empirically, such as the "big five." PMID- 1620784 TI - An exploratory study of funeral cost for suicides. AB - Funeral cost was less for younger people and for cremation. Among 156 funerals examined, after matching for sex, age, and cremation/burial, the funerals of a small sample of 6 suicides cost less than those of the controls. PMID- 1620785 TI - Identifying Hispanic gifted children using the Screening Assessment for Gifted Elementary Students. AB - We examined the utility of the Screening Assessment for Gifted Elementary Students (SAGES) for identifying Hispanic gifted students among 162 third through fifth graders, of whom 75% were Anglo-American and 25% Hispanic. Direct discriminant analysis of subscale scores of the SAGES classified 93.2% of the sample as Anglo-American, including 35 of the 41 Hispanic children. This indicated that the subscale scores did not predict group membership. A validation procedure yielded similar results on an independent sample of 25 Anglo-American and 14 Hispanic children. Also, a multivariate profile analysis indicated small score differences between the two groups and reflected similar cognitive processes being assessed. The screening device appears to function fairly within both ethnic groups. PMID- 1620786 TI - Relationship of the MacAndrew Scale to sensation seeking. AB - Findings of Baker, Beer, and Beer on use of the MacAndrew Scale in relating sensation seeking to alcoholism require comment. It is argued that the MacAndrew Scale does not provide interval level data below the cut-off score so correlations on such data should be point biserial. PMID- 1620787 TI - Informational feedback and self-esteem among male and female athletes. AB - The self-esteem of male and female competitive athletes was compared after each was provided either positive or negative (verbal) informational feedback on a nonathletic task, a series of single-solution anagrams. Subjects were 50 men and 50 women, aged 18 to 25 years, who were tested on the semantic differential to estimate athletes' self-esteem before and after receiving the informational feedback. Over-all, female athletes responded more strongly to both feedback conditions, with both groups being more influenced by negative rather than by positive feedback. PMID- 1620788 TI - Comment on Witherspoon, Long, and Nickell's study of speaking anxiety, self esteem, crime, and educational achievement. AB - Witherspoon, Long, and Nickell (1991) did not convincingly demonstrate that anxiety about speaking was related to dropping out of school or to the types of crimes that inmates commit. These authors did not control for variables related to these behaviors, and they did not compare the anxiety levels of the most appropriate groups of persons. PMID- 1620789 TI - Personality and scientific promise. AB - This study examined personality characteristics of 21 boys and 11 girls, children gifted in science and attending a junior high school. Differences between these boys and girls in Grade 6 were noted. Implications for teaching and directions for future research are noted. PMID- 1620790 TI - Infantile stimulation produces mild enhancement in a primary humoral response of adult albino rats. AB - Rat pups from 12 litters were handled daily, once every three days, or never touched between postnatal Days 5 and 20. At 100 days of age, 20 days after inoculation with human serum albumin, trunk blood was obtained to measure the antigen binding capacity (ABC). Rats handled as infants displayed relative immunofacilitation compared to those that had not been handled; the effect explained 7% of the variance in ABC values. In comparison, sex differences explained 14% of the variance. The results support the hypothesis that early disruptions in mother-infant bonding increase the likelihood of developing allergic responses following exposure to novel antigens during adulthood. PMID- 1620791 TI - The malevolent personality disorder? AB - The identification of any new psychopathology or syndrome has been based on numerous clinical enquiries and theoretical discussions and has assumed an important place in the literature of psychology and psychiatry. Using two case descriptions and the subject described in a recent book, this report presents a theoretical discussion of an unusual personality organization, referred to as the malevolent personality disorder. Differential diagnosis, theorizing about pathogenesis, clarification of salient psychodynamics, and treatment considerations are explored. PMID- 1620792 TI - Shyness, egocentricity, and psychopathology: their relationships among nonhospitalized individuals and mental hospital patients. AB - To investigate the relationship between shyness and egocentricity in both psychiatric (hospitalized) and nonhospitalized groups, 162 adult men and women diagnosed as paranoid or undifferentiated schizophrenic, and a control group of 162 nonhospitalized individuals matched for age and gender were studied. Shyness was assessed on the Social Reticence Scale and egocentricity by the Self-focus Sentence Completion. Analysis indicated that the patients were more shy than nonhospitalized individuals. Paranoid schizophrenics were not different from undifferentiated schizophrenics on egocentricity and the Self-focus Sentence Completion subscales. Nonhospitalized individuals and the mental hospital patients were egocentric on the Self-focus Sentence Completion. For this reason, relationships among shyness, egocentricity, and psychopathology could not be demonstrated. PMID- 1620793 TI - The generation effect in primed word-fragment completion reexamined. AB - Two experiments were designed to test a claim made by Gardiner (1988) that there are generation effects in implicit memory as measured by word-fragment completion. Subjects either read words at study or generated the words from fragments. As in previous research, fragments were completed to a greater extent if they were identical at study and test than if they differed. In Experiment 1 it was found that subjects could recognize explicitly the exact form of fragments that had been used for self-generation and distinguish these from other forms of fragments. An analysis of the contingency relations between recognition of fragments and fragment completion showed a high degree of dependence between the two tests. In Experiment 2 it was found that the match of surface features between study and test was a necessary, but not sufficient, condition to produce enhancement of priming. The results are interpreted as supporting the claim that generation does involve a data-driven component in addition to semantic elaboration. PMID- 1620794 TI - Memory monitoring and memory performance: linked closely or loosely? AB - An experimental test of the metamemory hypothesis claiming a substantive positive relationship between memory monitoring and memory performance is provided. Forty eight university students learned a set of abstract nouns. They were either instructed to make use of monitoring activities (experimental group), simply to learn the words (control-1) or to use non-metacognitive learning strategies (control-2). Prior to recall, the subjects had to predict the number of items they expected to remember. The experimental predictions were derived on two levels. First, prediction accuracy should be best for the experimental group. This is a necessary prerequisite for a valid test of the second prediction, namely that memory performance, too, should be best for the experimental group. Whereas the first prediction was confirmed, the second, vital for the metamemory hypothesis, was not. Thus, this hypothesis did not stand up to an experimental test, but would have been confirmed if tested by the correlation between prediction accuracy and memory performance. PMID- 1620795 TI - Productive and perceptual constraints on speech-error correction. AB - Two incentives underlie the present study on speech-error detection and correction. First, this area of research has up to now almost completely been approached through experimental techniques. Since it is not all clear whether speakers' detection and correction behaviour is identical inside and outside the laboratory, a comparison is made between experimental and naturalistic data. While the experimental materials are taken from the literature, the naturalistic findings are based upon the analysis of a corpus of more than 6,000 German slips of the tongue. It is shown that the same trends emerge in both data sets, thereby confirming the ecological validity of the experimental, and the reliability of the naturalistic, results. Secondly, the question arises as to the reasons for error correction and its occasional failure. Two working hypotheses are explored. Speakers fail to correct their errors because they have not detected them or because they assume that the error does not interfere with the listener's decoding process. The former reason is understood as a productive, the latter as a perceptual, constraint on the correction of self-produced errors. The empirical analysis discloses a large overlap between the effects of perceptual and productive constraints. However, whereas perceptual constraints can be subsumed under productive ones, the reverse is not possible. On the basis of this outcome it is argued that productive constraints are primary, and perceptual constraints secondary, reference points for error correction. Although the empirical data do not require the postulation of perceptual constraints, it is suggested that both speaker- and listener-based aspects form part of a highly integrated processing system. PMID- 1620796 TI - The effect of one night without sleep on problem-solving and immediate recall. AB - The aim of the study was to investigate the effect of spending one night without sleep on the performance of complex cognitive tasks, such as problem-solving, in comparison with a purely short-term memory task. One type of task investigated was immediate free recall, assumed to reflect the holding capacity of the working memory. The other type of task investigated was represented by syntactical reasoning and problem-solving tasks, assumed to reflect the processing (the mental transformation of input) and monitoring capacity of the working memory. Two experiments with a repeated-measures design were performed. Experiment 1 showed a significant decline in performance as a function of sleep loss on Raven's progressive matrices, a problem-solving task. No other main effect of sleep loss was found. Experiment 2 had a different order between tasks than Experiment 1 and the time without sleep was increased. A number-series induction task was also used in Experiment 2. A significant, negative effect of sleep loss in performance on Raven's progressive matrices was found in Experiment 2. The effects of sleep loss on the other tasks were nonsignificant. It is suggested that Raven's progressive-matrices task reflects the ability to monitor encoding operations (selective attention) and to monitor mental "computations". PMID- 1620797 TI - The right-hemisphere bias in conditional reasoning: a short report on multiple failures to replicate previous findings. AB - The present set of studies attempted to replicate Gellatly's (1985) findings that were supportive of Evan's (1982) hypothesis that the right hemisphere produces a selective bias towards the incorrect solution of a complex reasoning task. Subjects solved problems of the form "if p then q." In four studies, participants simultaneously performed a bottle--balancing task on each hand to interfere with processing of the reasoning task in the right hemisphere. In the fifth study, the bottle--balancing task was replaced by a finger--sequencing task. The results of the five studies did not show that the interference with right-hemisphere activity resulted in better performance on the conditional-reasoning task. It is concluded that the hypothesis of a right-hemisphere bias in conditional reasoning is still in need of reliable findings. PMID- 1620798 TI - Asymmetry of perceived key movement in chorale sequences: converging evidence from a probe-tone analysis. AB - In a probe-tone experiment, two groups of listeners--one trained, the other untrained, in traditional music theory--rated the goodness of fit of each of the 12 notes of the chromatic scale to four-voice harmonic sequences. Sequences were 12 simplified excerpts from Bach chorales, 4 nonmodulating, and 8 modulating. Modulations occurred either one or two steps in either the clockwise or the counterclockwise direction on the cycle of fifths. A consistent pattern of probe tone ratings was obtained for each sequence, with no significant differences between listener groups. Two methods of analysis (Fourier analysis and regression analysis) revealed a directional asymmetry in the perceived key movement conveyed by modulating sequences. For a given modulation distance, modulations in the counterclockwise direction effected a clearer shift in tonal organization toward the final key than did clockwise modulations. The nature of the directional asymmetry was consistent with results reported for identification and rating of key change in the sequences (Thompson & Cuddy, 1989a). Further, according to the multiple-regression analysis, probe-tone ratings did not merely reflect the distribution of tones in the sequence. Rather, ratings were sensitive to the temporal structure of the tonal organization in the sequence. PMID- 1620799 TI - A perceptual investigation of polytonality. AB - Four experiments investigated the perception of tonal structure in polytonal music. The experiments used musical excerpts in which the upper stave of the music suggested a different key than the lower stave. In Experiment 1, listeners rated the goodness of fit of probe tones following an excerpt from Dubois's Circus. Results suggested that listeners were sensitive to two keys, and weighted them according to their perceived importance within the excerpt. Experiment 2 confirmed that music within each stave reliably conveyed key structure on its own. In Experiment 3, listeners rated probe tones following an excerpt from Milhaud's Sonata No. 1 for Piano, in which different keys were conveyed in widely separate pitch registers. Ratings were collected across three octaves. Listeners did not associate each key with a specific register. Rather, ratings for all three octave registers reflected only the key associated with the upper stave. Experiment 4 confirmed that the music within each stave reliably conveyed key structure on its own. It is suggested that when one key predominates in a polytonal context, other keys may not contribute to the overall perceived tonal structure. The influence of long-term knowledge and immediate context on the perception of tonal structure in polytonal music is discussed. PMID- 1620800 TI - The effect of a non-informative cueing signal in a three-choice reaction-time task. AB - Many studies have shown that in a simple reaction-time (RT) task a non informative leading cue decreases RT to a subsequent target presented in the same region as the cue. This facilitation lasts about 150 ms; it is then replaced by a sustained inhibition. Experiment 1 tests the hypothesis that the initial facilitation is due to motor, rather than perceptual, processes by using choice RT. Facilitation is greater and lasts longer in choice than in simple tasks, thus supporting the hypothesis. Experiment 2 shows that facilitation occurs even when the subject actively orients his or her attention away from the cue. PMID- 1620801 TI - Subitizing: magical numbers or mere superstition? AB - It is widely believed that humans are endowed with a specialized numerical process, called subitizing, which enables them to apprehend rapidly and accurately the numerosity of small sets of objects. A major part of the evidence for this process is a purported discontinuity in the mean response time (RT) versus numerosity curves at about 4 elements, when subjects enumerate up to 7 or more elements in a visual display. In this article, RT data collected in a speeded enumeration experiment are subjected to a variety of statistical analyses, including several tests on the RT distributions. None of these tests reveals a significant discontinuity as numerosity increases. The data do suggest a strong stochastic dominance in RT by display numerosity, indicating that the mental effort required to enumerate does increase with each additional element in the display, both within and beyond the putative subitizing range. PMID- 1620802 TI - Reading isolated words: no evidence for automatic incorporation of the phonetic code. AB - Backward masking with a homophonic mask induces better target recognition than backward masking with a graphemic mask that shares the same letters with the target as the homophonic mask. From this, the existence of automatic prelexical phonological recoding in silent word reading has been inferred. The present experiments, however, show that the advantage of homophonic masks in a backward masking task only arises if a considerable proportion of the masks are phonologically related to the targets (at least for Dutch). The results are in line with findings of lexical-decision tasks and number-processing tasks, and constitute a further argument for the dominance of the orthographic route over the phonological route in processing isolated written words. PMID- 1620803 TI - In-hospital injuries of medical and surgical patients: the predictive effect of a prior injury. AB - Four hundred three consecutive injury victims admitted via emergency ward over a 3-month period were tracked with 403 contemporaneous controls with medical illness and blindly assessed for in-hospital accidents. There was a high frequency of "incidents" (n = 161 in 107 patients, mainly falls and medication errors), but injury victim admissions resembled medically ill controls when compared by the Kaplan-Meier method for cumulative probability of occurrence of an in-hospital incident. Accelerated failure/time models using the Weibull method to compute average times from admission to incident showed little difference between groups. Admission type (injury victim vs. control) did not predict psychiatric consultation, incident type, or multiple incidents in hospital. Although the injury group had a larger proportion of males and lower mean age, stratification to control for age and sex did not significantly discriminate injury victims from controls in production of incidents: Over all risk of incidents was random. By studying patients during a hospital stay, the effects of differences in individual environment and drug and alcohol intoxication are largely factored out; under these conditions the predictive effect of a prior injury becomes insignificant. In-hospital injury is associated with host factors long known to promote falls: increasing age, debility-cum-mobility, and central nervous system depressant medication. PMID- 1620804 TI - Anxiety and endocrine responses to surgery: paradoxical effects of preoperative relaxation training. AB - It has been argued that surgery is a form of psychological stress, and that the response to it should therefore be modifiable by psychological means. To test this hypothesis, we assessed the effect of preoperative relaxation instructions on endocrine, cardiovascular, and subjective responses in 21 patients undergoing minor abdominal surgery. Controls (N = 19) received general procedural information. In the relaxation group only, there was a significant increase in cortisol and adrenaline concentration from immediately before induction of anesthesia to immediately after surgery. Noradrenaline values were unaffected by relaxation. In contrast, relaxation reduced state-anxiety on the preoperative day and the two postoperative days; maximal peroperative systolic and diastolic blood pressures were also reduced. The results are consistent with previous evidence that adrenaline and cortisol responses to surgery are greater in less anxious patients. PMID- 1620805 TI - Lactate infusion induces panic attacks in patients with premenstrual syndrome. AB - A sodium lactate test was performed during the premenstrual phase in 35 women suffering from prospectively confirmed premenstrual syndrome (PMS) and in 16 controls in order to assess whether these patients were sensitive to this test and whether this sensitivity was accounted for primarily by the presence of concomitant panic disorder. Patients with PMS also underwent the Structured Clinical Interview for the DSM-III-R (SCID) to determine the presence of co morbid anxiety and/or mood disorders. Only 31% of the PMS patients were free from a depressive/anxiety disorder, while nine patients met criteria for panic disorder, and the remaining 15 subjects were diagnosed as having anxiety and/or mood disorders. Lactate infusion induced panic attacks in 22 subjects (62.9%) and two controls (12.5%). Panickers were equally distributed among PMS patients with or without a concurrent anxiety/mood disorder. Although cardiovascular responses to lactate were similar among PMS patients regardless of the presence of concomitant anxiety/mood disorders, both plasma cortisol levels and panic and mood scores were higher during the test in those patients with concomitant panic disorder. These results suggest that PMS patients display an increased sensitivity to lactate, which is not primarily accounted for by the presence of co-morbid panic disorder. PMID- 1620806 TI - Gender, anger expression style, and opportunity for anger release determine cardiovascular reaction to and recovery from anger provocation. AB - This study represents an extension of Hokanson's research, which showed that for men anger release after provocation tends to accelerate cardiovascular recovery. The objective of this study was to investigate how gender and habitual style for anger-in or anger-out behavior modulate the effect of anger provocation and release. Male and female subjects (N = 105) were classified as anger-in/anger-out only when a double criterion (i.e., self-report and peer evaluation) was satisfied. Following a state anger rating at pre-test, subjects were harassed during the performance of a 12-minute math task. After task completion, subjects were randomly assigned to one of two 10-minute recovery protocols a) having an opportunity to release negative affect, and b) not not having such an opportunity. All groups (including the anger-ins) that had an opportunity to express negative affect did in fact express similar levels of anger. Men reacted more strongly to the math task performed under anger provocation on all cardiovascular indices. Anger expression style as a trait-type disposition was important for the recovery process in women whereas the situational manipulation (i.e., the opportunity to release anger) had specific effects on the recovery process of men. Opportunity to release anger facilitated heart rate recovery (and to a lesser degree diastolic pressure recovery) in men but not in women. Women with anger-in tendencies on the other hand displayed better systolic pressure recovery than female anger-outs whereas no such effects were observed in men. PMID- 1620807 TI - Dimensions of hostility in men, women, and boys: relationships to personality and cardiovascular responses to stress. AB - Ratings of Potential for Hostility and Hostile Style based on responses during the Type A Structured Interview (SI) are related to incidence of coronary heart disease morbidity and mortality. As there are very limited data on what precisely the SI ratings of hostility mean, the present study evaluated, in a sample of middle-aged men and women, and adolescent boys, a) the distributions of SI ratings of hostility according to gender and age group; b) their relationships to other hostility and personality scores; and c) their relationships to heightened cardiovascular responses to psychological stressors, which are thought to be a major mechanism linking behavior and coronary heart disease. Results showed that men are higher than women and boys in Potential for Hostility and Hostile Style ratings, which are, by and large, unrelated to standardized questionnaire measures of hostility and anger expression. Men (but not women or boys) who exhibited elevated systolic blood pressure during standardized laboratory stressors tended to be rated as high on Hostile Style. We conclude that SI Hostile Style ratings are measuring a unique aspect of personality, one with apparent importance for coronary heart disease and perhaps for men's cardiovascular responses during stress. PMID- 1620808 TI - Social support in social interaction: a moderator of cardiovascular reactivity. AB - This study examines the possibility that social support operates as a moderator of cardiovascular reactivity, which may be a factor in the development of heart disease and hypertension. An experiment was performed in which each of 40 subjects was the object of verbal attack in a discussion of a controversial issue. In each session, one subject and three confederates participated. Two of the confederates argued with the subject; in half the groups, a third confederate defended the subject's position (social support condition); in the other half, the third confederate sat quietly (no support condition). The subject's blood pressure and heart rate were continuously monitored. Subjects in the social support condition showed significantly smaller increases in cardiovascular measures than subjects in the no support condition. The results are discussed in terms of small group dynamics and Social Comparison Theory. PMID- 1620809 TI - The relationship between job strain and blood pressure at work, at home, and during sleep. AB - Eleven normotensive workers in "high strain" jobs, defined by the combination of high psychological work load and low worker control, were compared with 26 normotensive workers in "low strain" jobs on ambulatory blood pressure (BP) at work, at home in the evening, and during sleep. High strain workers' systolic BP was higher at work and at home in the evening, after adjusting for prework casual BP, body mass index, gender. Type A behavior, and caffeine consumption. Under certain conditions, systolic BP during sleep and diastolic BP at work were higher as well. Men and women, and Type A and Type B workers, were indistinguishable in job strain effects on BP. Type A workers tended to hold "active" (high demand, high control) jobs, and Type B workers "passive" jobs. More research is needed to distinguish more clearly job strain as 'cause' of observed BP effects from job strain as mere 'correlate.' PMID- 1620810 TI - Effects of coffee on cardiovascular responses to stress: a 14-week controlled trial. AB - We studied the cardiovascular responses to orthostatic and mental stress of 43 healthy subjects who daily received six cups of boiled or filtered coffee and of 21 healthy subjects who abstained from caffeine-containing beverages. All 64 subjects first received six cups of filtered coffee/day for 2 weeks. Then blood pressure (BP) and heart rate (HR) were recorded before, during, and after a "stand upright" test and a mental arithmetic test. Subjects were then randomized to either complete abstinence from caffeine-containing beverages (n = 21), or consumption of six cups of filtered coffee (n = 21), or consumption of six cups of boiled coffee/day (n = 22). The stress tests were repeated after subjects had been on these regimens for 8 weeks. Abstinence from coffee did not affect the responses of BP or HR to orthostatic stress, or the response of BP to mental stress. The increase in HR caused by mental stress was five beats/min less (p = 0.02) in the no-coffee group than in the filtered- (95% confidence interval -8.8 to -1.2) or boiled- (95% confidence interval -8.4 to -0.8) coffee group. It is concluded that elimination of caffeine decreases the HR response to mental stress. PMID- 1620811 TI - Further analysis of the psychometric properties of the Levine Denial of Illness Scale. AB - This study contributes cross-validational data with regard to the Levine Denial of Illness Scale from a sample of 152 hospitalized myocardial infarction patients. A factor analysis and subsequent examination of the data yielded four usable factors of denial termed: Cognitive Denial of Illness, Denial of Impact on Future, Denial of Need for Care, and Affective Denial. In an analysis of subscale correlations, these four factor-based scales were related, but distinguishable, thus supporting the idea of the multidimensionality of denial. Furthermore, these factors were not related to demographic variables. Correlating these four scales with standardized measures of affect indicated that it can be useful in research to distinguish between several types of denial of illness in myocardial infarction patients. PMID- 1620813 TI - Epidemiology of Crohn's disease in Indian migrants and the indigenous population in Leicestershire. AB - A retrospective, epidemiological community study of Crohn's disease was performed in Leicestershire from 1972 to 1989. The county population of 930,000 includes 93,000 South Asians. Potential cases were identified from hospital departments of pathology, endoscopy and medical records, in addition to general practitioners. There were 582 cases in Europeans and 28 in South Asians. The incidence of Crohn's disease in Europeans and South Asians has increased, particularly in Muslims. The standardized incidence in South Asians during the 1980s was 2.4/10(5)/year in Hindus, 3.4/10(5)/year in Sikhs and 5.4/10(5)/year in Muslims. The standardized incidence in Europeans has risen significantly to 4.7/10(5)/year from 3.4/10(5)/year in the 1970s (chi 2 = 8.1, p less than 0.005). In Leicester this increase can be accounted for entirely by new cases of colonic disease. All ethnic groups had a similar disease distribution. Small bowel disease was inversely associated with age, whilst colonic disease increased with age. However, the difference in age-specific incidence of Crohn's disease for different age bands at various sites was not significant. Overall, Hindus have a much lower incidence of Crohn's disease than Europeans. PMID- 1620812 TI - Type II essential mixed cryoglobulinaemia: presentation, treatment and outcome in 13 patients. AB - The long-term clinical course of patients with primary Type II essential mixed cryoglobulinaemia is unclear as many reports fail to separate this group from patients with Type III disease. We have reviewed 13 patients with Type II essential mixed cryoglobulinaemia who presented to the Hammersmith Hospital between 1976 and 1990. All patients had a cryoglobulin level greater than 0.1 mg/ml (range 0.27-6.50 mg/ml), and characterization of the cryoglobulin in all cases revealed the presence of a monoclonal IgM kappa component with rheumatoid factor activity together with polyclonal IgG. All patients had evidence of activation of the classical pathway of complement with greatly reduced levels of C4, while C3 levels were moderately reduced in three patients. All patients had skin disease and joint symptoms were reported by nine patients, with erosive arthritis in one. Eight patients had peripheral sensorimotor neuropathy. Renal disease was observed in 10 patients, manifesting as raised creatinine level, proteinuria or haematuria. Renal tissue was examined in eight patients: in six the appearances were those of a mesangiocapillary glomerulonephritis Type I while in the other two patients there was a mesangioproliferative glomerulonephritis, in one diffuse and in the other focal and segmental. Glomerular capillary 'hyaline thrombi' were found in six biopsies, extracapillary proliferation was found in three and evidence of vasculitis was found in all eight. Liver biopsy showed macronodular cirrhosis in one patient, while a second with recurrent episodes of jaundice showed only chronic inflammatory changes. No patient was positive for hepatitis B surface antigen; however one patient had low titre anti hepatitis B surface antibody. Normochromic normocytic anaemia was present in nine patients. Bone marrow examination was carried out in 13 patients at presentation to our unit: 10 showed no evidence of a lymphoproliferative disorder, while three suggested the presence of a non-Hodgkin's lymphoma (some years after original presentation in all three). Unusual clinical features included one patient with retinal vasculitis and one patient with severe pulmonary haemorrhage. PMID- 1620814 TI - Mortality in systemic sclerosis (scleroderma). AB - Two hundred and thirty-seven patients with systemic sclerosis were followed prospectively in a scleroderma clinic. The overall 3, 6, and 9-year survival rates were 86, 76 and 61 per cent respectively. Renal, cardiac and pulmonary disease, and older age at enrollment were adverse prognostic factors associated with reduced survival. There were no significant differences in survival between males and females or in patients with restricted compared to those with diffuse skin thickening. Death from systemic sclerosis was most frequently due to pulmonary hypertension, with fewer than expected deaths from renal or cardiac causes. Twenty-eight per cent of deaths were due to causes unrelated to systemic sclerosis, most commonly cancer and ischaemic heart disease, and in older patients. PMID- 1620815 TI - Risk stratification for dissemination of tuberculosis in HIV-infected patients. AB - The location of tuberculosis (TB) early in the course of HIV-induced immunosuppression was located, and an attempt was made to determine the correlation between the degree of immune suppression and prognostic variables to stratify the risk for dissemination of TB in HIV-infected patients. Clinical and laboratory characteristics were reviewed in 73 HIV-infected patients with TB admitted between 1984 and 1990. The presence of Mycobacterium tuberculosis was investigated in different clinical samples to verify the diagnostic yield of different sources. TB was extrapulmonary in 46.6 per cent of patients in whom it was their first opportunistic infection, and in 46.7 per cent of patients with previously diagnosed AIDS (p = NS). TB was frequently associated with other opportunistic infections, particularly oesophageal candidiasis (p = 0.006). Patients with localized extrapulmonary or disseminated TB presented more often with cytopenias, hypoalbuminaemia and oral thrush. The existence of extrapulmonary TB or another opportunistic coinfection allowed AIDS to be diagnosed in the same admission in 30 patients and a mean of 8.4 months later in another eight. Extrapulmonary TB was found to be as common in early HIV infection as in patients with established AIDS. Haematological derangements were common in these patients, and cytopenias, hypoalbuminaemia and oral thrush were useful predictors of TB dissemination. The location of TB and its dissemination were not significantly linked to a more advanced CDC stage of HIV infection or a more profound fall in CD4 count.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620816 TI - The diagnosis of intra-abdominal abscesses in patients with severe Crohn's disease. AB - A series of 24 patients with severe relapses of Crohn's disease responding poorly to conventional treatment with corticosteroids was studied to determine the incidence of intra-abdominal abscesses and the best means to detect them. Ultrasound scans proved to be difficult to interpret and unreliable. Computed tomography demonstrated abnormal bowel thickening in most cases, and showed seven of the eight intraabdominal abscesses. 111In leucocyte scintigraphy always demonstrated inflamed areas of bowel, but underestimated the extent of disease in three patients and overestimated it in five. All eight abdominal abscesses were detected, and there were no false-positive results. It was always possible to distinguish the abscess from inflamed bowel wall. Intra-abdominal abscess is not uncommon in patients with severe relapses of Crohn's disease which are not responsive to corticosteroid therapy, being present in about one-third of patients. 111In leucocyte scintigraphy is a simple and helpful test for differentiating between active inflammatory bowel disease and complicating abscesses, contributing significantly to the management of patients with severe Crohn's disease. PMID- 1620817 TI - An outbreak of multiresistant Salmonella typhi in South Africa. AB - Typhoid fever caused by Salmonella typhi remains endemic to many parts of South Africa, including Natal and KwaZulu, Northern Transvaal and the Transkei. Until recently, the majority of S. typhi isolates from South Africa have remained susceptible to ampicillin/amoxycillin and chloramphenicol, and only three cases of typhoid due to multi-antibiotic resistant strains of S. typhi have been documented. Ampicillin/amoxycillin and chloramphenicol are, therefore, still recommended as first line therapy for patients with typhoid fever in this country. We describe a cluster of six cases of typhoid caused by S. typhi that was resistant to ampicillin, chloramphenicol and trimethoprim-sulphamethoxazole. All these patients presented over a 3-month period; the patients were from three adjacent districts in the Northern Natal area of South Africa. The high rate of intestinal perforation (two of six) was a direct consequence of inappropriate antibiotic treatment. Failure of surgical intervention, renal impairment as well as delay in starting appropriate antibiotic treatment were factors contributing to the high mortality (three of six). The good clinical outcome in the remaining three patients probably resulted from treatment with appropriate antibiotics; however, mild disease in two of these patients may have been a contributing factor. All isolates showed high minimal inhibitory concentrations (MIC) of greater than or equal to 256 micrograms/ml to ampicillin, chloramphenicol and trimethoprim-sulphamethoxazole. The isolates were all highly sensitive to the third generation cephalosporins (MIC less than or equal to 0.06 micrograms/ml) and quinolones (MIC less than or equal to 0.03 micrograms/ml). Conjugation studies suggest a genetic transfer of resistance, probably plasmid mediated. The presence of beta-lactamase and chloramphenicol acetyl transferase enzymes in all six isolates tested would account for the resistance to ampicillin and chloramphenicol respectively. The transfer of such plasmids to erstwhile sensitive strains could conceivably occur in this typhoid-endemic area, where sanitary conditions are poor and living conditions crowded, thus further exacerbating the problem. It is recommended that in areas where such multiresistant strains are encountered, the third generation cephalosporins or quinolones be used as empiric therapy for typhoid fever. PMID- 1620818 TI - Small bowel malabsorption: clinical and radiologic perspectives. How we see it. PMID- 1620819 TI - To follow or not to follow, that is the question. PMID- 1620820 TI - Doppler US evaluation of renal artery stenosis: past, present, and future. PMID- 1620821 TI - 1991 RSNA special focus session on "the new health care": impact on radiologists. PMID- 1620822 TI - Relationships between radiology and industry: accomplishments, opportunities, and ethical concerns. PMID- 1620823 TI - Chemoirradiation: a new initiative in cancer treatment. 1991 RSNA annual oration in radiation oncology. AB - The use of concomitant continuous infusion chemotherapy and radiation therapy in the treatment of a variety of tumors has produced, in relatively limited clinical experience, substantial improvements in complete response and survival rates. Although there is still a need to establish the most effective combinations, concentrations, and scheduling of drugs, as well as optimum dose and fractionation of radiation, a number of benefits have already been recorded with this approach. Organ preservation is maximized in all but the most advanced cancers of the anus, esophagus, and bladder. In advanced head and neck cancers, particularly in the paranasal sinuses when bone destruction and infiltration have occurred, the total dose required for effective therapy can be reduced by 15% 30%, which substantially lowers the rate of complications. Therapeutic gains have also been seen in the treatment of other primary and recurrent gastrointestinal and gynecologic malignancies and their hepatic metastases. Finally, there is considerable potential for this approach in the treatment of bulky or recurrent soft-tissue sarcomas, particularly in the extremities. PMID- 1620824 TI - Results of radical perineal prostatectomy with adjuvant brachytherapy. AB - Retrospective analysis of outcome in 137 patients who underwent radical perineal prostatectomy and bilateral injection of gold-198 implants into the periprostatic tissues and/or neurovascular pedicles as treatment for prostatic adenocarcinoma was performed. Patients had undergone treatment between 1975 and 1985. Local recurrence developed in 22 patients (16.1%) and distant metastases developed in 33 (24.1%). Clinical and surgical staging of disease and Gleason grading of pathologic specimens were performed retrospectively. Kaplan-Meier local recurrence, freedom from relapse (FFR), and survival rates decreased with increasing stage and pathologic grade. With clinical staging, these rates were not statistically different from previous rates achieved with external beam radiation therapy, and with pathologic staging, they were not statistically different from previous rates achieved with prostatectomy. The authors conclude that (a) 5-year follow-up is inadequate to determine local control rates after prostatectomy; (b) use of implants did not improve local control, FFR, or survival rates of 10 years; and (c) method of staging probably has more effect on local control, FFR, and survival rates than does treatment modality. PMID- 1620825 TI - Patent ductus arteriosus: transcatheter closure with a transvenous technique. AB - Transvenous closure is described of the patent ductus arteriosus with a conical device that consists of polyurethane foam mounted on a stainless steel frame. 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 entry-site 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- 1620826 TI - Short-term response to thrombolytic therapy in deep venous thrombosis: predictive value of venographic appearance. AB - To determine whether the response to thrombolytic therapy for lower-extremity deep venous thrombosis (DVT) can be predicted from the venographic appearance, 139 thrombosed venous segments were analyzed. Initial and follow-up venograms were obtained in 62 patients randomized to 24-hour infusions of recombinant human tissue-type plasminogen activator (rTPA) (n = 34), rTPA plus heparin (n = 16), or heparin alone (n = 12). Segmental response to therapy was evaluated by means of blinded review of the paired venograms. The response (50%-100% lysis) to rTPA alone was significantly greater in venous segments involved with nonobstructive thrombi than in those with obstructive thrombi (12 of 23 vs five of 51; P less than .005). Results were similar for the combination of rTPA and heparin (five of six vs six of 30, P less than .01). No significant difference was seen in the response of either obstructive or nonobstructive thrombus to heparin alone. Thrombotic tails responded substantially (greater than 50% decrease in size) to rTPA with or without heparin in 22 of 24 patients. The venographic appearance of DVT appears to help in predicting the therapeutic response to thrombolytic therapy. PMID- 1620827 TI - Gadolinium-enhanced magnitude contrast MR angiography of popliteal and tibial arteries. AB - To evaluate the efficacy of gadopentetate dimeglumine in MR angiography of the lower extremities, a flow phantom, seven healthy volunteers, and seven patients with peripheral vascular disease were studied with a magnitude contrast (MC) technique. The combination of an MC rephase-dephase gradient-refocused-echo pulse sequence, a 40-cm-long transmit-receive coil, and intravenous administration of a bolus of gadopentetate dimeglumine improved MR angiographic quality in the phantom, volunteers, and patients. Gadolinium enhancement decreased deleterious saturation effects and improved images of the popliteal and tibioperoneal arteries in the volunteers and patients. However, in some cases, venous overlap, imaging artifacts, and suboptimal visualization of subtle lesions limited interpretation. The authors conclude that gadolinium enhancement combined with an MC subtraction pulse sequence appreciably improves MR angiography of lower extremity arteries. PMID- 1620828 TI - Assessment of intracardiac shunts with gadolinium-enhanced ultrafast MR imaging. AB - Dye dilutional techniques are widely accepted for the assessment of intracardiac shunts, but current techniques require arterial access or radioisotope injection. Ultrafast (less than 500 msec) magnetic resonance (MR) imaging is ideally suited for the evaluation of an indicator during passage through the heart. Twenty patients were studied, including 13 with shunts. Four-chamber, T1-weighted images were obtained during bolus injection of gadopentetate dimeglumine. A single image was obtained in 420 msec, with repetitive images acquired after each QRS complex. After the contrast material was injected, there was pronounced signal intensity enhancement in the right atrium, followed by the right ventricular cavity, left atrium, left ventricular cavity, and descending aorta. Patients with substantial intracardiac shunts demonstrated early recirculation. First-pass contrast material-enhanced MR imaging is a promising new technique for the rapid assessment of intracardiac shunts. Combined with anatomic and functional MR imaging techniques, it can help provide a comprehensive noninvasive evaluation of suspected intracardiac shunts or provide follow-up in patients with known shunts. PMID- 1620829 TI - Peripheral transcatheter embolization with platinum microcoils. AB - Embolotherapy with platinum microcoils delivered through the Tracker-18 microcatheter (Target Therapeutics, San Jose, Calif) was performed in 16 patients when peripheral superselective catheterization with standard angiographic catheters was not possible. The Tracker-18 catheter could be directed distally into small peripheral vessels for delivery of the microcoils. These microcoils, with attached fiber strands, resulted in vascular occlusion within a few minutes in all cases. Embolotherapy was technically successful in all patients. The procedures were clinically successful in 15 of 16 patients (94%), and no complications were encountered. Embolization with platinum microcoils through the Tracker-18 catheter is useful when standard methods of embolization are not possible. PMID- 1620830 TI - Corrosive esophageal stricture: safety and effectiveness of balloon dilation. AB - The safety and long-term effectiveness of fluoroscopically guided balloon dilation for corrosive esophageal stricture was evaluated in 22 patients with a follow-up period of more than 1 year (range, 13-52 months). The average interval between corrosive agent ingestion and initial balloon dilation was 18 years (range, 2 months to 51 years). Balloons with a diameter of 5-8 mm were used in the initial attempt. The caliber of the balloon catheter was increased gradually over subsequent dilations, up to a diameter that allowed patients to swallow solid foods. Dilation of more than 17 mm in diameter was performed in five patients. Patients underwent one to five sessions. Esophageal rupture occurred in seven patients and was treated nonoperatively in five and surgically in two. With exclusion of these latter two, 11 of 20 could tolerate swallowing all kinds of food and nine could tolerate swallowing most foods. Balloon dilation in corrosive esophageal strictures is effective, but the high rupture rate indicates the need for extra caution. PMID- 1620831 TI - Effect of varying rates of low-osmolarity contrast media injection for hepatic CT: correlation with indocyanine green transit time. AB - Contrast enhancement in hepatic computed tomography (CT) is related to multiple factors, including the amount of iodine injected, the rate of injection, and body weight. Fifty patients were randomized into two groups: 19 patients (group 1) received a 160-mL dose of Optiray 320 (ioversol) at 3.0 mL/sec, and 31 (group 2) received the same dose at 4.5 mL/sec. Indocyanine green dye transit time, peak enhancement, delayed enhancement, time to peak enhancement, age, and weight were statistically analyzed. Time to peak enhancement was significantly shorter in group 2 than in group 1 (62 seconds vs 73 seconds, respectively; P less than .01). Peak contrast enhancement averaged 88 HU +/- 19 in group 1 and 99 HU +/- 17 in group 2 (P = .06). Circulation time did not correlate with peak enhancement and thus does not assist in tailoring contrast medium injection for hepatic CT. Injection of contrast material at 3.0 and 4.5 mL/sec provides greater hepatic CT contrast enhancement than previously reported, with no significant risk of subcutaneous extravasation when injection is monitored carefully. These higher levels of contrast enhancement may assist in detecting and characterizing hepatic lesions. PMID- 1620832 TI - Comparative randomized double-blind study of hydroxyzine versus placebo as premedication before injection of iodinated contrast media. AB - The use of ionic contrast media in radiologic examinations may cause a wide variety of anaphylactoid reactions. The aim of this double-blind randomized study was to determine whether a simple and inexpensive premedication based on an antihistamine could reduce the number of idiosyncratic reactions in 400 patients (251 men and 149 women) without a clinical history of allergy who were to receive an intravenous injection of a low-osmolality iodinated contrast medium. Twelve hours before examination, a group of 200 patients was given one 100-mg tablet of hydroxyzine; another group of 200 was given a placebo tablet under the same conditions. Results in the two groups were comparable at the .05 level of significance. Twenty-five patients in the placebo group had a reaction (mainly urticaria); only two patients in the hydroxyzine group had a reaction (P less than .0001; odds ratio, 14.1). No severe reaction occurred in either group. Because hydroxyzine and placebo were allocated at random, it is concluded that hydroxyzine reduces the frequency of minor anaphylactoid reactions in patients at low risk. PMID- 1620833 TI - Ionic iodinated contrast medium and amobarbital sodium mixtures: potential for precipitation. AB - When a small amount of diatrizoate meglumine, an ionic iodinated contrast medium, is left in a catheter system before injection of amobarbital sodium or when the contrast medium is intentionally mixed with amobarbital sodium, a potentially dangerous situation occurs. The authors showed in vitro that a dense precipitate forms in this situation. This is due to an acid-base reaction between the relatively acidic contrast medium and basic barbiturate and the subsequent formation of insoluble amobarbital. PMID- 1620834 TI - Ameloblastoma in the maxillomandibular region: MR imaging. AB - Nine patients suspected of having primary ameloblastoma of the mandible or maxilla and five patients with clinical and/or radiologic indications of postoperative recurrence of ameloblastoma were examined with magnetic resonance (MR) imaging. In the former, results were compared with those of conventional radiography, computed tomography (CT), and pathologic analysis. Seven tumors were multilocular; two were unilocular. MR imaging showed a mixed pattern of solid and cystic components (n = 9), irregularly thick walls (n = 9), and papillary projections (n = 6). MR imaging was superior to conventional radiography and CT in demonstrating these findings. However, shell-like bulgings of the bone cortex were demonstrated more effectively with conventional radiography and/or CT in six cases, and soft-tissue invasion was overestimated with MR imaging in four cases. All tumors except one showed strong enhancement of solid components including papillary projections, walls, and septa at enhanced MR imaging. In the latter group of patients, MR imaging correctly demonstrated recurrence in two and no recurrence in three. PMID- 1620835 TI - Improved time-of-flight MR angiography of the brain with magnetization transfer contrast. AB - The authors hypothesized that magnetization transfer contrast (MTC) could be used to improve flow contrast in time-of-flight (TOF) magnetic resonance (MR) angiography. Two- and three-dimensional flow-compensated gradient-echo images were obtained with and without MTC. MTC images were obtained by applying low power radio-frequency (RF) radiation with a frequency offset from the bulk "free" water resonance frequency before the excitation RF pulse. The signal intensity of stationary tissue decreased as the power applied for the MTC pulse was increased. A smaller decrease occurred in venous signal intensity as measured in the superior sagittal sinus, and less change was seen in the arterial signal intensity as measured in the middle cerebral artery. Cerebrospinal fluid showed no MTC effect. The use of MTC improved small-vessel depiction on maximum intensity projection images. The authors conclude that use of MTC can substantially enhance the quality of TOF MR angiography of the brain. PMID- 1620836 TI - Carotid arteries: evaluation with low-field-strength MR angiography. AB - Magnetic resonance (MR) angiography of neck vessels was performed with a 0.2-T permanent magnet by using a two-dimensional, time-of-flight technique. Thirty-one patients were included in the study. The imaging parameters used included a repetition time of 60 msec, an echo time of 10 msec, a 90 degrees flip angle, and a 192 x 256 matrix; 40-50 sequential two-dimensional sections were acquired through the neck. Stenosis was graded on a scale of 1-5. Correlation of digital and MR angiography was made in the clinically nonrelevant cases (stenoses of grades 1 and 2), with overestimation to grade 3 in six cases. Two grade 3 stenoses were overestimated as grade 4. Severe stenoses were correctly characterized in all but one case, which was underestimated because of a segmental short extension of the stenotic lesion. Obstructions were found in two cases. Areas with a lack of signal were observed in four patients with severe stenosis and in two with tortuous arteries. Correct diagnosis, however, was achieved with analysis of the maximum intensity projection animation display. Low field-strength MR angiography has the same clinical value as that performed with high field strengths. PMID- 1620837 TI - Proximal cervical spinal nerve: MR appearance. AB - An interradicular cleft and a segment of nerve containing fascicles have recently been described in the cervical spinal nerve. This study was performed to determine whether the fascicles and the interradicular cleft have a distinctive appearance on magnetic resonance (MR) images. The proximal spinal nerves and nerve roots of C-4 and C-8 were removed from cadavers, imaged with MR, sectioned, and stained. Cervical neural foramina were imaged with MR and then sectioned. The MR images demonstrated a division of the root sheaths into ventral and dorsal portions, separated by fat within the interradicular cleft and located proximal to the dorsal root ganglion. Distal to the dorsal root ganglion, the proximal portion of the cervical spinal nerve containing multiple fascicles gave the proximal portion of the spinal nerve an inhomogeneous appearance on the MR images. This study suggests an anatomic explanation for the variable appearance of the cervical spinal nerves with MR imaging. PMID- 1620838 TI - Nonpalpable, probably benign lesions: role of follow-up mammography. AB - Of 21,855 consecutive women prospectively studied with mammography, physical examination, and high-resolution ultrasonography when appropriate, 558 received a diagnosis of nonpalpable, probably benign lesions. Follow-up mammography was recommended for these patients. Characteristically benign lesions and palpable masses were excluded from analysis. The positive predictive value for detection of a nonpalpable, probably benign breast lesion was 0.017. Nine patients ultimately proved to have carcinoma; two of them had noninvasive carcinoma, and two had axillary node metastases. The positive predictive value for detection of a nonpalpable, probably malignant lesion was 0.47. The policy of recommending mammographic surveillance for nonpalpable, probably benign lesions, a viable option for radiologists, has the capability of lowering the rate and therefore the costs of biopsy procedures with negative results. PMID- 1620839 TI - Mobile mammographic screening of self-referred women: results of 22,540 screenings. AB - In this mass screening mammography program, self-referred women are accepted for screening only if part of a sponsoring organization. Screening is performed with mobile equipment, often at the work site. Of the first 22,540 screenings, 61% (n = 13,784) were of women aged 35-49 years. Eighty-nine percent (n = 20,025) of the screenings were normal. Of 51 women in whom cancer was found, 38 (75%) were recommended for biopsy on the basis of their initial two-view mammogram. The prevalence of breast cancer generally increased with advancing age but was similar between women aged 35-39 years and those aged 40-49 years. Of the 28 women with complete histologic studies, 43% (n = 12) had pure intraductal cancer and another 43% had negative findings at axillary node dissection. Program costs dictated a $65 fee. Within the design of this program it has been possible to screen large numbers of self-referred women and detect early carcinomas. Program design, however, may make screening more expensive than in a fixed screening site accepting only physician-referred women. PMID- 1620840 TI - Enlarging fibroadenoma in a postmenopausal woman: case report. AB - The authors describe mammographic and pathologic evidence of the growth of a fibroadenoma in an 82-year-old obese woman, 44 years after menopause, who had never been treated with hormone therapy. The patient's obesity is hypothesized as the causal factor for increased estrogen levels leading to growth of the fibroadenoma. PMID- 1620841 TI - In vivo relaxation times and hydrogen density at 0.063-4.85 T in rats with implanted mammary adenocarcinomas. AB - Magnetic resonance (MR) imaging at 0.063 T, 0.17 T, 0.35 T, 2.94 T, and 4.85 T was performed in rats with implanted mammary adenocarcinomas (and in control rats) to study hydrogen density and the effects of magnetic field strength on T1 and T2 relaxation times in vivo. T1 increased by an order of magnitude and T2 decreased by a factor of two between the lowest and highest field strengths. Only about half of the increased water content of tumor, compared with that of muscle, was reflected in increased hydrogen density. The sensitivity of relaxation time change was increased at the lower field strengths. These results are of significance in understanding the effects of field strength on lesion detectability, contrast, and signal-to-noise ratio. PMID- 1620842 TI - Pulmonary nodular opacities after transbronchial biopsy in patients with lung transplants. AB - Focal nodular opacities were seen on 26 of 74 (35%) postbiopsy radiographs obtained in 39 patients who underwent lung transplantation. The subsequent clinical course and diagnostic evaluation suggested that the opacities were due to focal hemorrhage at the biopsy sites. This finding was evident on only three of 40 (8%) postbiopsy radiographs obtained in 40 control patients who underwent transbronchial biopsy for diffuse interstitial lung disease. The differential diagnosis of new pulmonary nodular opacities in lung transplantation patients should include focal postbiopsy hematomas, because of their relatively frequent occurrence in this clinical situation. PMID- 1620843 TI - Tracheal and bronchial cartilaginous rings: warfarin sodium-induced calcification. AB - Progressive calcification of the cartilaginous rings (CCR) of the trachea and bronchi has been observed in patients undergoing prolonged prophylactic anticoagulant therapy with warfarin sodium. The purpose of this study was to validate the relationship of warfarin sodium and CCR, as well as to present the appearance and sex and age distribution of the normal degenerative CCR seen in the elderly. Chest radiographs were scrutinized for evidence of CCR in 92 patients who underwent warfarin sodium therapy and in 105 patients used as a control group. CCR was classified as not present (scored as 0), subtle (scored as 1), and extensive (scored as 2). In the warfarin sodium study group, 47% of patients (43 of 92) exhibited level 1 or level 2 CCR. This proportion was 19% (20 of 105) in the control group. The difference was statistically significant (P less than .001). A significant positive correlation (P less than .001) was also present between the duration of warfarin sodium therapy and increased levels of CCR. PMID- 1620844 TI - Solitary pulmonary nodules: detection of malignancy with PET with 2-[F-18]-fluoro 2-deoxy-D-glucose. AB - It is estimated that nearly one-third of solitary pulmonary nodules (SPNs) may represent bronchogenic carcinoma. The noninvasive imaging methods used currently (ie, plain radiography, computed tomography) are not reliable for accurate detection of malignancy in most SPNs. The authors prospectively evaluated use of positron emission tomography (PET) with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) for identification of malignancy in 20 patients with noncalcific, radiographically indeterminate SPNs. PET-FDG imaging demonstrated focal hypermetabolism in 13 biopsy-proved malignant nodules, whereas no increased FDG uptake was seen in the seven benign SPNs. Semiquantitative analysis with computation of differential uptake ratios also helped clearly differentiate benign nodules (mean +/- standard deviation, 0.56 +/- 0.27) from malignant nodules (mean +/- standard deviation, 5.63 +/- 2.38) (P less than .001). Thus, PET-FDG imaging may be a potentially useful noninvasive technique for accurate differentiation of benign and malignant SPNs that are radiographically indeterminate. PMID- 1620845 TI - Fibrosing alveolitis: chest radiography and CT as predictors of clinical and functional impairment at follow-up in 26 patients. AB - Findings on the original and follow-up chest radiographs and computed tomographic (CT) scans were correlated with clinical and functional parameters in 26 patients with fibrosing alveolitis. Assessment of chest radiographs included determination of a standard profusion score and an average profusion score. The CT assessment included pattern, extent, and distribution of disease. The standard profusion score showed no significant correlation with clinical or functional parameters (P greater than .05). However, the average profusion score of the six lung zones correlated with severity of dyspnea and with static lung volumes (P less than .01). Extent of irregular linear opacities on CT scans correlated with severity of dyspnea and impairment in gas transfer (carbon monoxide-diffusing capacity) (P less than .01). The profusion of ground-glass opacities on the radiograph showed no significant correlations (P greater than .05). The profusion and extent of ground-glass opacities on CT scans correlated with severity of dyspnea, impairment in gas transfer, and reduction in static lung volumes (P less than .01). Ground-glass opacities on CT scans preceded and predicted the development of irregular linear opacities on follow-up CT scans and correlated with an increase in the average profusion score of the chest radiograph (P less than .01). PMID- 1620846 TI - Fibrosing alveolitis: prognostic implication of ground-glass attenuation at high resolution CT. AB - To evaluate the prognostic implication of ground-glass attenuation at high resolution computed tomography (HRCT) in assessing response to treatment in fibrosing alveolitis, the authors correlated HRCT findings with the improvement in pulmonary function, as represented by the increase in percentage predicted values on pulmonary function tests after corticosteroid therapy. Nineteen patients underwent HRCT before treatment and pulmonary function testing before and after treatment. The HRCT scans were reviewed by two independent observers. Areas of ground-glass attenuation were quantified subjectively by using a 0%-100% scale with 10% increments. The extent of ground-glass attenuation at HRCT was significantly correlated with improvement in diffusing capacity for carbon monoxide (r = .67, P = .0019), forced vital capacity (r = .71, P = .0007), and forced expiratory volume in 1 second (r = .64, P = .0034) after steroid treatment. These results suggest that ground-glass attenuation at HRCT is a good predictor of response to treatment in fibrosing alveolitis. PMID- 1620847 TI - Prospective validation of the stripe sign in ventilation-perfusion scintigraphy. AB - The data base of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) was used to test the accuracy of the stripe sign for the exclusion of embolic perfusion defects on lung scintigrams. Lung scan readings showed the presence and location of this sign in 50 (4.7%) of 1,064 patients. Perfusion defects showing the stripe sign were not associated with pulmonary embolism in the same lung zone (upper, middle, or lower third of each lung) in 93% (79 of 85) of instances. Thirty-eight percent (n = 32) of lung zones with the stripe sign had associated chest radiographic abnormalities, and 69% (n = 59) had ventilation scan abnormalities. Formulation of the scan diagnosis according to PIOPED criteria showed fewer indeterminate readings in patients with the stripe sign and without pulmonary embolism when the stripe sign was used. Use of the sign changed diagnosis in less than 1% of the total population, however, because of its low overall prevalence. The stripe sign is a useful adjunct to standard criteria in the interpretation of pulmonary scintigrams for evaluation of suspected acute pulmonary embolism. PMID- 1620848 TI - Communication between the two pleural cavities after major cardiothoracic surgery: relevance to percutaneous intervention. AB - The authors describe evidence of communication between the two pleural cavities after major cardiothoracic surgery (combined heart and lung transplantation, heart transplantation, and correction of complex congenital heart disease) performed in three patients. In two patients, unilateral lung biopsy caused a symptomatic bilateral pneumothorax. This was successfully treated with insertion of a single chest tube in one patient and two chest tubes in the other patient. In the third patient, simultaneous evacuation of large bilateral pleural effusions was performed by means of unilateral thoracentesis because of the presence of a common pleural cavity. PMID- 1620849 TI - Neuroblastoma: dose-related sensitivity of MIBG scanning in detection. AB - Iodine-131 metaiodobenzylguanidine (MIBG) has shown effectiveness as a systemic radiotherapeutic agent in neuroblastoma. The authors postulated a likely dose related relationship of MIBG sensitivity when it was administered for neuroblastoma detection. They studied this relationship in neuroblastoma patients who underwent scanning after receiving diagnostic and therapeutic doses of MIBG in temporal proximity. Seven patients with stage IV disease received a total of 14 therapeutic administrations of I-131 MIBG (150-350 mCi [5,550-12,950 MBq]/m2 per treatment). Posttherapy scans were obtained at 3 and at 5-7 days. Diagnostic MIBG scans had been obtained no more than 4 weeks before the start of therapy. Use of diagnostic MIBG scanning led to underestimation of the tumor burden by 50% compared with use of posttherapy scanning. This difference may be an important consideration in selecting therapeutic strategies for individual patients. It further suggests that use of much larger diagnostic doses of MIBG is a rational strategy in histologically confirmed cases of advanced disease. PMID- 1620850 TI - Age dependency of the renal resistive index in healthy children. AB - It has recently been suggested that the resistive index (RI) in native kidneys of healthy children is age dependent; however, this relationship has not been completely defined or explained. In 110 kidneys in 71 healthy children aged newborn to 11 years, RIs were determined from peripheral sites (presumed to be arcuate, cortical, or distal interlobar arteries). The authors found the normal renal RI (the mean RI in each kidney) to be age dependent. The renal RI in children is commonly elevated above the upper normal limit in adults (0.70) in the 1st year of life, and the overall trend shows a decrease with age. From 4 years on, the likelihood is low (2% probability) that the RI is above 0.70. Variability of the renal RI from individual to individual was most marked in the first 6 months of life, with 51% (19 of 37) of these kidneys having an RI that would be considered abnormal by adult standards. It is concluded that the normal renal RI is age dependent, with an overall decreasing trend with increasing age. This age dependency of the renal RI and, hence, of the renal vascular resistance might be dependent on levels of active renin, as the maturational profile of the renal RI more closely parallels that of active renin than those of other renal functional parameters. PMID- 1620851 TI - Renal arterial stenosis: slowed systole in the downstream circulation- experimental study in dogs. AB - To test the effect of stenosis of the renal artery on the downstream intrarenal blood flow, a snare was placed around the renal artery in 10 dogs and compressed to create stenosis while Doppler curves were obtained from interlobar arteries. Pulsed Doppler examination of the segmental and interlobar arteries was performed by means of placement of a 7.5-MHz mechanical sector transducer directly on the surface of the kidney. The following calculations were made: degree of stenosis (evaluated with aortography), acceleration index (AI) (the acceleration of systole), and resistive index. The Doppler measurements were compared with findings on angiograms. The AI for normal arteries ranged from 2.2 to 4.3, and for arteries with 75% or greater stenosis, from 1.0 to 1.3. Systolic peaks disappeared as near occlusion was achieved. These changes were reversible within seconds of release of the arterial snare. Such change is identical to change in the pulsus tardus and parvus waveforms seen in both acute and chronic severe stenosis of the renal artery in humans. PMID- 1620852 TI - Stenosis of the renal artery: assessment of slowed systole in the downstream circulation with Doppler sonography. AB - Slowing and dampening of systole in the arterial network distal to stenosis is a well-known Doppler sign of severe arterial stenosis. To determine whether this sign is present in boys and girls with such stenosis, intrarenal Doppler curves (acceleration index [AI] and resistive index [RI]) were compared with findings on renal arteriograms in 20 boys and girls; the AI was also measured in 10 boys and girls without renal disease. Statistical analysis of AI and RI measurements was performed. Eleven of 32 renal arteries were normal. The normal AI was 4.0-7.0; in arteries with greater than 75% stenosis, the AI was 0.7-1.7. In five arteries studied after angioplasty, the AI had changed from 0.7-1.5 to 4.0-5.6 at the first posttreatment examination (performed 28 hours to 1 week after angioplasty), and it remained normal during the 3-year follow-up period. In kidneys with stenotic arteries, the RIs were lower (0.43-0.54) than in healthy subjects (0.56 0.63). Regression and correlation coefficients of AI and RI measurements were statistically significant, and discrimination between normal arteries and those with greater than 75% stenosis was excellent. PMID- 1620853 TI - Segmental stenosis of the renal artery: pattern recognition of tardus and parvus abnormalities with duplex sonography. AB - Segmental renal artery branches within the renal sinus were prospectively evaluated with color Doppler imaging and pulsed-Doppler spectral analysis in 56 patients before angiography. Waveforms were evaluated for the tardus and parvus abnormalities of prolonged acceleration time, diminished acceleration index, and loss of the normal early systolic compliance peak/reflective-wave complex (ESP). Findings obtained with these parameters were compared with the subsequent findings on angiograms to ascertain their efficacy in detection of hemodynamically significant (greater than or equal to 60%) renal arterial stenosis (RAS), which was present in 32 kidneys in 26 patients. Simple pattern recognition analysis of ESP proved to be the best of the three parameters. Loss of ESP enabled identification of RAS with 95% sensitivity, 97% specificity, a 92% positive predictive value, a 98% negative predictive value, a 96% overall accuracy. On the basis of the high technical success rate, high sensitivity and specificity, and short examination time, waveform analysis for detection of tardus-parvus abnormalities, especially loss of ESP, of the segmental artery is recommended as an alternative to direct examination of the main renal arteries for evaluation of RAS. PMID- 1620854 TI - Small renal cell carcinoma: pathologic and radiologic correlation. AB - The authors correlated the radiologic and pathologic findings of 36 patients with small renal cell carcinoma (less than or equal to 3 cm in diameter). Tumors were discovered incidentally or by means of mass surveys with ultrasound (US). Computed tomography (CT) and angiography were performed before surgery. Of the 36 tumors, 24 were of solid (alveolar) architecture, five were of papillary architecture, three were of tubular architecture, and four were of multilocular cystic architecture. Cell arrangement was closely correlated with radiologic appearance, especially in regard to tumor vascularity and echogenicity. Histologically homogeneous tumors of solid architecture were hypoechoic at US and hypervascular at angiography and contrast medium-enhanced CT. Tumors of papillary, tubular, and multilocular cystic architecture were hyperechoic at US and hypovascular at angiography. There was no correlation of cell differentiation and cell architecture with echogenicity or tumor vascularity. Tumors with hemorrhage showed marked hyperattenuation at CT. A tumor capsule was observed in 25 patients (69%); this was demonstrated as a rim at US or angiography. PMID- 1620855 TI - MR imaging of the most commonly injured ankle ligaments. Part I. Normal anatomy. AB - To determine the optimum foot position and imaging plane at magnetic resonance (MR) imaging of each ankle ligament, 10 cadaver ankles were dissected to visualize the orientation, precise attachment sites, and relationships of each ligament. Then eight cadaver ankles were studied with MR imaging and were cryosectioned in the optimum imaging planes. The ankles of 12 healthy volunteers were imaged to ensure consistency in identifying the normal ligaments. With the foot taped into full dorsiflexion of 10 degrees-20 degrees, axial imaging provided optimum views of the anterior, posterior, and inferior tibiofibular ligaments and of the anterior and posterior fibulotalar ligaments and provided an overview of the deltoid ligament. Coronal images provided full-length views of the tibiospring, tibiocalcaneal, and posterior tibiotalar parts of the deltoid ligament. With the foot taped into full plantar flexion of 40 degrees-50 degrees, axial imaging optimized visualization of the fibulocalcaneal ligament and of the tibionavicular and anterior tibiotalar parts of the deltoid ligament. Sagittal images provided the best full-length views of the spring ligament. PMID- 1620856 TI - MR imaging of the most commonly injured ankle ligaments. Part II. Ligament injuries. AB - Thirteen patients with clinically diagnosed sprained ankles underwent magnetic resonance (MR) imaging. Five of these cases are presented to illustrate the potential of MR imaging to enable identification of both primary and associated ligament injury sites, grading of the severity of the injuries, and visualization of the associated findings of tendon sheath and joint effusion. The appropriate combination of foot position and imaging plane is essential to achieve full length visualization of each ligament. Two patients demonstrated findings compatible with total gross disruption of the anterior fibulotalar ligament; two, with injury to the fibulocalcaneal ligament with effusion of the overlying peroneus tendon sheath; and one, with thinning, lengthening, and fibrotic changes involving the anterior fibulotalar ligament. MR imaging can provide a noninvasive means to evaluate the site and severity of ankle ligament injuries (a) in acute ankle injuries that demonstrate significant instability, (b) in stable acute injuries involving athletes or litigation, or (c) in patients with repeated injuries or instability in whom surgery is contemplated. PMID- 1620857 TI - SLAP lesions of the glenoid labrum: CT arthrographic and arthroscopic correlation. AB - Tears in the superior part of the glenoid labrum in the anterior and posterior directions (SLAP, superior labrum anterior, posterior) result from injuries that place excessive stress on the tendon of the long head of the biceps brachii muscle. The intimate relationship of the tendon and the superior glenoid labrum promotes injury to the latter structure. Four types of SLAP lesions are seen at arthroscopy. Images from 17 patients with surgically proved SLAP lesions who had undergone preoperative computed tomographic (CT) arthrography were retrospectively reviewed to evaluate the value of CT arthrography in the detection and accurate depiction of these labral injuries. The authors compared the findings at videotaped arthroscopic surgery with those from CT arthrography and found that abnormalities of the labral-capsular apparatus could be detected with CT arthrography in 16 of the 17 patients. Furthermore, the CT arthrographic criteria developed during this review helped determine the type of tear in 15 of the 17 patients. CT arthrography appears to be useful in the evaluation of patients with suspected SLAP lesions. PMID- 1620858 TI - MR imaging of the normal shoulder: variants and pitfalls. AB - In 30 volunteers with normal shoulders, the following conclusions were made with regard to normal anatomic features at magnetic resonance (MR) imaging: (a) The supraspinatus tendon has low signal intensity, except for a 1-cm area with intermediate signal intensity in the region of the "critical zone." (b) The deltoid tendon attachment on the inferior surface of the acromion may simulate a subacromial spur if not imaged in continuity. (c) Fluid in the long head of the biceps tendon sheath is normal if not completely surrounding the tendon. (d) The anterolateral branch of the anterior humeral circumflex vessels in the proximal bicipital groove adjacent to the biceps tendon mimics fluid in the tendon sheath. (e) Continuity or obliteration of the subacromial-subdeltoid bursal fat plane is an unreliable diagnostic sign since the fat plane is often focally absent. (f) Fluid is not detected in subacromial-subdeltoid bursae. (g) Undercutting of the anterior glenoid labrum by hyaline cartilage or a closely apposed middle glenohumeral ligament may simulate an anterior labral tear. PMID- 1620859 TI - MR imaging of the elbow. AB - Of 27 patients who underwent magnetic resonance (MR) imaging of the elbow, 11 underwent elbow arthroscopy and/or an open surgical procedure. Surgical findings were compared with those from MR imaging. Five healthy volunteers also underwent MR imaging to demonstrate anatomic relationships. Transchondral fracture (osteochondritis dissecans) was identified in three of the 11 patients and was proved at surgery. Loose bodies were suspected at MR imaging in the three patients but were found in only two. One complete avulsion of the ulnar collateral ligament (UCL) and four cases of intact, thickened UCLs were identified at MR imaging and surgery. Loose bodies from the olecranon tip were found in three patients at surgery but were seen on MR images in only two. MR imaging depicted olecranal osteophytes in three cases, which were confirmed at surgery. Two complete avulsions of the biceps tendon and one partial triceps tendon tear were identified with MR imaging and proved at surgery. A postoperative soft-tissue infection and a synovial cyst were also seen at MR imaging and surgery. These results suggest that MR imaging is useful in the evaluation of the elbow. PMID- 1620860 TI - Reflex sympathetic dystrophy in the foot: clinical and scintigraphic criteria. AB - To establish strict clinical criteria for reflex sympathetic dystrophy (RSD) of the foot and to characterize any associated scintigraphic pattern, the authors performed three-phase radionuclide bone scanning in 51 patients prospectively referred because RSD was a diagnostic consideration. To establish sensitivity and specificity data, the cases of an additional 100 consecutive patients referred for a variety of foot problems were retrospectively reviewed. The authors defined RSD of the foot as a pain syndrome characterized by diffuse nonanatomic, often unrelenting pain; autonomic-vasomotor signs including warm or cool skin temperatures and moist-sweaty or dry-scaly skin; and a positive response to a lumbar sympathetic block. Patients with RSD have a characteristic delayed bone scan pattern consisting of diffuse increased tracer throughout the foot, with juxta-articular accentuation of tracer uptake. Overall, sensitivity in this study was 100%; specificity, 80%; positive predictive value, 54%; and negative predictive value, 100%. False-positive images were obtained in patients with infection, diabetes, and chronic pain. Specificity was 66% in the subgroup of patients who underwent sympathetic block, with a positive-predictive value of 88%. There were no differences in scan pattern related to duration of symptoms prior to imaging. PMID- 1620861 TI - Salmonella colitis: assessment with double-contrast barium enema examination in seven patients. AB - To completely rule out the possibility of ulcerative colitis, Crohn disease, and other diseases, the authors analyzed the radiographic findings at double-contrast barium enema examination performed in seven patients with colitis caused by Salmonella organisms. In all patients, bacteriologic confirmation of nontyphoid Salmonella infection and radiographs of the upper gastrointestinal tract were obtained. Total colonoscopy was performed in five patients and sigmoidoscopy in one patient. In all patients, the radiographic findings were retrospectively analyzed. The descending colon and sigmoid colon were affected in six patients, whereas the rectum was affected in none. The findings included fine mucosal granularity (seven patients), loss of haustration (six patients), many fine ulcerations (five patients), and multiple ulcers (two patients). The radiographic features simulated those of ulcerative colitis, except for absence of rectal abnormality. It is concluded that double-contrast barium enema examination is useful for detection of fine mucosal changes. PMID- 1620862 TI - Crohn disease of the small intestine: accuracy and relevance of enteroclysis. AB - The accuracy and clinical relevance of enteroclysis in the evaluation of 138 patients referred for enteroclysis for suspected Crohn disease of the small intestine are reported. The original prospective interpretations of enteroclysis results were assessed after a clinical follow-up period of 2 or more years. With all patients considered, enteroclysis had a sensitivity, specificity, and accuracy of 100%, 98.3%, and 99.3%, respectively, with only one false-positive diagnosis and no false-negative diagnoses. Thirty-one percent (n = 43) of the patients had lesions of early Crohn disease. All patients who required surgery (n = 23) had advanced lesions of the disease, according to enteroclysis criteria. Clinical evidence of Crohn disease did not develop in the 58 patients in whom enteroclysis revealed no abnormality. There were no complications related to the procedure. It is concluded that enteroclysis is an accurate method for diagnosis and exclusion of Crohn disease of the small intestine and provides detailed structural information relevant to appropriate management of the disease. PMID- 1620863 TI - Pelvic prolapse: assessment with evacuation proctography (defecography) AB - The contribution of evacuation proctography (EP) to the evaluation of pelvic prolapse was assessed in 74 consecutive patients. A rectocele was demonstrated in 73 patients (99%); large rectoceles frequently showed barium trapping, but there was no correlation between these findings and rectal symptoms. An enterocele was detected at evacuation proctography in 13 patients (18%) (including two enteroceles seen only retrospectively), and a sigmoidocele was shown in four patients (5%). Physical examination resulted in detection of only seven enteroceles and of none of the sigmoidoceles. In 48 patients (65%), additional findings were evident at EP, including excessive pelvic floor descent, anal incontinence, rectal intussusception, and spastic pelvic floor. These data suggest that EP is particularly useful in the preoperative evaluation of pelvic prolapse if the patient has anorectal symptoms or is at risk for an enterocele. EP contributes to surgical planning by enabling identification of clinically unsuspected enteroceles and sigmoidoceles and coexistent disorders of rectal evacuation. PMID- 1620864 TI - Perirectal lymph nodes in rectal cancer: in vitro correlation of sonographic parameters and histopathologic findings. AB - Preoperative staging of lymph nodes in patients with rectal cancer is essential for selecting the most appropriate therapy. To determine the discriminating value of all ultrasound parameters described in the literature, the authors obtained high-frequency sonograms of 43 lymph nodes in 21 resected rectal specimens, thereby simulating the in vivo situation. Univariate analysis revealed that inhomogeneity (P less than .0005), short axis diameter (P less than .005), and hilar reflection (P less than .01) were helpful in differentiating between metastatically involved and noninvolved lymph nodes. A prognostic trend was seen for long-axis diameter (P = .05), roundness index (P = .09), and echogenicity (P = .05). With stepwise logistic regression analysis, inhomogeneity and hilar reflection were selected as being independently discriminative. Inhomogeneity is a parameter with a high specificity; hilar reflection is particularly sensitive. No clear differentiation could be made, however, in a sizable proportion of lymph nodes (60%). The prospective use of especially these significant parameters in vivo is recommended to determine their ultimate value in preoperative staging. PMID- 1620865 TI - Gaucher disease: abdominal MR imaging findings in 46 patients. AB - Abdominal magnetic resonance imaging findings were reviewed in 46 patients with Gaucher disease. All patients had hepatosplenomegaly at the time of initial imaging. Splenic nodules were present in 14 patients (30%) and varied in signal intensity. These nodules were isointense on T1-weighted and hypointense on T2 weighted images. Splenic infarcts were seen in 15 patients (33%), and four of these patients (9%) also had subcapsular fluid collections. Both nodules and infarcts were present in the spleen in four patients (9%). Pathologic correlation was performed with specimens from two patients who underwent partial splenectomy. Focal areas of abnormal signal intensity were noted in the liver in nine patients (20%). They were either stellate or segmental, and may represent fibrotic septa with ischemic changes associated with aggregates of Gaucher cells. No changes were noted in the kidneys or abdominal lymph nodes. PMID- 1620866 TI - Solid and papillary epithelial neoplasm of the pancreas: MR imaging and pathologic correlation. AB - Correlation of magnetic resonance (MR) imaging findings and those at pathologic evaluation was attempted in six cases of solid and papillary epithelial neoplasm of the pancreas. All patients were female, and the mean patient age was 26 years (range, 13-73 years). On T1-weighted spin-echo images, tumors were well demarcated, and areas of high signal intensity were evident within them. At macroscopic examination, these areas corresponded to solid portions with marked hemorrhagic necrosis or cystic portions filled with hemorrhagic debris. In three of four masses surrounded by macroscopically evident fibrous capsules, a rim of low intensity was revealed at T1-weighted imaging. When T1-weighted spin-echo imaging reveals obvious areas of high intensity within a sharply marginated tumor of the pancreas, especially in a young woman, solid and papillary epithelial neoplasm might be a primary diagnostic consideration. PMID- 1620867 TI - Use of film duplicator to lighten dark radiographs. AB - The authors introduce a simple technique for lightening overexposed or overdeveloped dark radiographs. With the technique, an increase of exposure time in film duplicator allows production of duplicate radiographs with an appropriate tone. With this manipulation, image details are greatly improved, and the original radiograph is not damaged. PMID- 1620868 TI - Kinematic MR imaging of the patellofemoral joint: comparison of passive positioning and active movement techniques. AB - Thirteen patients underwent magnetic resonance (MR) imaging of the patellofemoral joint in an evaluation of passive positioning and active movement kinematic MR imaging techniques. Sixteen joints were symptomatic, and 10 were not. Delineation of normal and abnormal patellar alignment and tracking was similar with the two techniques, but kinematic MR imaging performed with active movement allowed a substantial reduction in examination time while permitting evaluation of the contribution of associated activated muscles and soft-tissue structures to patellofemoral joint function. PMID- 1620869 TI - Improving acceptance of barium by children by using milk for dilution. PMID- 1620870 TI - Percutaneous drainage of hydatid liver cysts. PMID- 1620871 TI - Cerebellar dimensions in assessment of gestational age in neonates. PMID- 1620872 TI - The nature of science and discovery. PMID- 1620873 TI - Radiologists, clinicians, and patient care. PMID- 1620874 TI - Metabolic needs, utilization and dietary sources of fatty acids in childhood. AB - Fatty acids are molecules that differ in the length of their carbon chain and the number of double bonds within them. Each of the resulting "families" has its own peculiarities as regards energy, structure and metabolism. Passing from the short, saturated chains to the very long polyunsaturated ones produces an increasing degree of specialization in metabolic and structural functions important for the body's development and general homeostasis. The fetus and neonate (especially if preterm), the breast-fed and weaning baby all need fatty acids in the right amounts and ratios to achieve full expression of their genetic growth potential, especially of nerve tissues. Intake in these age groups depends on dietary factors such as the mother's diet during pregnancy, the type of milk (human or artificial), and the weaning schedule. Later in childhood and in adolescence not only must the body's somatic growth needs be covered, but intake must be adequate to lay the basis for prevention of chronic-degenerative pathologies. Dietary recommendations are therefore based on encouraging a normocaloric feeding pattern, with a controlled total and saturated lipid proportion and balanced intake of unsaturated fatty acids. PMID- 1620875 TI - Nutrition challenge for Asia. PMID- 1620876 TI - Nephrocalcinosis in the rat: a literature review. AB - Nephrocalcinosis is a common disorder in female rats. Various etiological factors are involved in the pathogenesis, e.g. sex, age, genetical and dietary factors. Dietary phosphorus concentration appears to be of crucial importance in the induction of nephrocalcinosis. The pathological changes in calcinotic kidney tissue are described. Possible mechanisms underlying nephrocalcinogenesis are discussed. Phosphorus concentration within the proximal tubule may be the major determinant of nephrocalcinogenesis. PMID- 1620877 TI - [Molecular mechanism for the induction of cyclooxygenase]. PMID- 1620878 TI - [Molecular structure and evolution of cyclooxygenase and lipoxygenase]. PMID- 1620879 TI - [Prostaglandin and cell differentiation]. PMID- 1620880 TI - [Molecular/regulatory mechanisms of the action of prostaglandins and related compounds in the central nervous system]. PMID- 1620881 TI - [Regulation of chromatin structure and its transcriptional activity by histone acetylation]. PMID- 1620882 TI - An updated dose-response analysis in Hodgkin's disease. AB - Although radiotherapy cures a very high percentage of early stage patients with Hodgkin's disease (HD), there is a controversial dichotomy in the dose recommendations believed necessary to achieve greater than 95% local control: Whereas one school of thought is to administer 40-44 Gy, other reports claim equal results with about 36 Gy. It is also not clear what doses are required for various tumor cell burdens. The original recommendation of 40-44 Gy was derived from a retrospective analysis of in-field control of disease from mostly kilovoltage data three decades ago. However, there have been many advances in the evaluation of the extent of the disease and in the practice of radiotherapy since the 1960s. Many more dose-control studies have been published in recent years, necessitating a revisit to the dose-response question in HD. Here we have compiled the dose-control data from the 60s to the 90s and analyzed the original and the updated data with the same statistical method to see any differences. We also have performed similar analysis of dose-control information for subclinical disease, less than 6 cm and greater than 6 cm disease. Whereas original analysis (1040 sites at risk) suggested 98% in-field control with 44 Gy, our re-analysis including modern megavoltage data (4117 sites at risk) shows that similar in field control rates could be achieved with 37.5 Gy. With megavoltage radiotherapy, the doses required for 98% in-field control for subclinical disease and disease of less than 6 cm and greater than 6 cm are, 32.4 Gy (1426 sites at risk), 36.9 Gy (1005 sites at risk) and 37.4 Gy (98 sites at risk), respectively. The results of current updated analysis will provide in-field disease control probabilities for different disease burdens and can serve as a guide in deciding dose prescriptions for practicing radiation oncologists. PMID- 1620883 TI - Localized extradural lymphoma: survival, relapse pattern and functional outcome. The Princess Margaret Hospital Lymphoma Group. AB - Between 1967 and 1988, 22 patients were treated at The Princess Margaret Hospital (PMH) for localized (stage IE) non-Hodgkin's lymphoma (NHL) presenting with spinal extradural compression. The median age of the patients was 55 years (range 18-76). Back pain (20 patients) and leg weakness (18 patients) were the commonest complaints at presentation. Seven patients (30%) were non-ambulatory (paraplegic or severely paretic) and four had imparied sphincter function. Diffuse histiocytic lymphoma (12 cases) was the commonest histology. All patients initially had laminectomy decompression and were referred to PMH post operatively. One patient (with coincident metastatic carcinoma of the breast) was treated palliatively. The remaining 21 patients received radical post-operative treatment: radiation therapy (XRT) alone in 12 cases (25-45 Gy), radiation therapy plus systemic combination chemotherapy (combined modality therapy, CMT) in 9 cases. The overall actuarial survival for the radically treated patients was 55% at 10 years and there was a significant difference (p = 0.037) between those treated by XRT alone (33%) and those who received CMT (86%). Only one patient from each treatment group failed locally but the distant recurrence-free survival for the XRT group was 32% compared to 100% for the CMT group (p = 0.017). One patient developed primary central nervous system (CNS) relapse. The functional results of treatment were excellent: 19 of the 21 radically treated patients regained or retained normal ambulatory status and the remaining two patients had only minor disability. Decompressive surgery and radiotherapy for localized extradural lymphoma ensures a high rate of local control and functional recovery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620884 TI - Post-irradiation hyperamylasemia as a biological dosimeter. AB - Serum alpha-amylase was measured before and 24 h after either total body (31 patients) or localized irradiation including the salivary glands (40 patients) or the pancreatic area (22 patients). A significant increase in amylasemia was observed for doses to the parotid glands larger than 0.5 Gy. A sigmoid function of dose was fitted to the data and predicted a maximum amylasemia level for doses larger than 4 Gy and smaller than 10 Gy. The raw data from other published series were adequately described by the same model. However, the confidence limits of the parameters remained wide, because of a considerable interindividual variability. Post-irradiation hyperamylasemia appears to provide a good criterion for triage of accidentally irradiated patients: 24 h after a dose larger than 2 Gy to the parotid glands, 91% of the patients had an amylasemia level higher than 2.5-fold the upper normal value (sensitivity). Conversely, 96% had their serum amylasemia lower than 2.5-fold the upper normal value when dose was smaller than 2 Gy (specificity). However, a retrospective estimation of the absorbed dose (dosimetry) is not likely to be very precise because of the large interindividual variability. PMID- 1620885 TI - Preoperative radiation therapy and surgery in the treatment of "bulky" squamous cell carcinoma of the uterine cervix (stage Ib, IIa, and IIb operable tumors). AB - Forty-two women with "bulky" squamous cell carcinoma of the uterine cervix, larger than 5 cm, were treated between 1982 and 1988. The median follow-up was 5 years (from 37 to 106 months). The age range was from 25 to 77 years (mean: 49). There were 14 stage Ib, 5 stage IIa, and 23 stage IIb operable patients. Forty grays were delivered at mid-plane of the pelvis (23 fractions in 31 days) using the four-field technique (6-18 MV). External beam radiation therapy was followed by 20 Gy of intracavitary radiation therapy. Forty-eight days later total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO) and bilateral pelvic lymphadenectomy were performed. The 3- and 5-year disease-free survival was 83 and 81%, respectively. The 5-year locoregional control rate was 83%. Thirteen patients suffered from mild to severe complications (31%) but there were only two long-term (5%) complications. PMID- 1620886 TI - The value of postoperative irradiation in renal cell cancer. AB - This is a retrospective analysis of 147 evaluable patients, with histologically proven renal cell carcinoma, who were referred to our center between 1977 through 1988. All patients with disease limited to the kidney underwent nephrectomy. Post operative megavoltage irradiation, with a median dose of 46 Gy, was given to 56 patients, using parallel opposing portals, or multiple field technique. Five and 10 year actuarial survivals in irradiated patients (Rt+) were 50 and 44%, respectively, and in non-irradiated patients (Rt-) 40 and 32%, respectively. The disease recurred locally in a total of 19 patients; 16 had tumor bed recurrence and three had scar recurrence. Local recurrence by stage was as follows: T2 N0M0: RT+ 0/17, RT- 2/28; T3 N0M0: RT+ 4/37 (10%), RT- 11/30 (37%) (p less than 0.05); T4 N0M0: RT+ 1/2, RT- 1/5. Two of the local recurrences in irradiated patients developed in a surgical scar which was not included in the treatment volume. Significant toxicity developed in three patients (5%). It is concluded that post operative irradiation can reduce local recurrence rate in T3 N0M0 renal cell carcinoma. It is recommended that the surgical scar should always be included in the treatment volume and irradiated to a full dose. PMID- 1620887 TI - Routine clinical on-line portal imaging followed by immediate field adjustment using a tele-controlled patient couch. AB - We have evaluated the fluoroscopic on-line portal imaging (OPI) system developed by Siemens (Beamview-1, Concord, CA, U.S.A.) in routine clinical radiotherapy, involving the treatment of 883 fields (559 patient set-ups for treatment) on 21 patients. The image was typically generated by delivering 10 monitor units when used in single exposure or 1-2 monitor units on a large open field followed by 8 10 monitor units on the actual field when double exposure was used. Comparison between the portal image and the simulator film was done by eye. A region of tolerance was drawn on the simulator film and the field edges on the portal image had to project within this region. If this criterion was not met, adjustments followed by verification portal images were done before the remaining field dose was delivered. If possible, these adjustments were performed by moving the patient couch by remote control. The image quality was insufficient for evaluation in 75/883 (8.5%) fields. The abovementioned criterion was not met in 95/808 (11.8%) of the evaluable fields (26/559 patient set-ups were not evaluable). Of the 533 evaluable patient set-ups, 92 had to be adjusted (17.2%) including three (pelvic irradiations) set-ups that were adjusted on both field irradiated during the same radiotherapy session. In one case an incorrect tray (with wrong blocks) was detected and replaced. In one case (a 5.5 x 6.0 cm rectangular larynx field) the x and y axis of the field were interswitched. In one case incorrect focusing of a block was shown by the portal image. To make adjustments, the couch longitudinal position was changed 20 times (range -10 to +15 mm). The lateral position was changed 73 times (range -15 to +16 mm). The height position was changes 6 times (range -7 to +6 mm). Diaphragma rotation changes were performed 5 times (1 degree). The fraction of treatment time that was related to the use of OPI was 30.7% median (mean 32.4%, S.D. 14.1%). The range was 4.1 to 78.6%. On the basis of calculations assuming no OPI would have been used, field treatment time was increased by a median of 44.2% (mean 55.8%; S.D. 41.2%) by using OPI. The fraction of monitor units (fraction of the dose) to generate a satisfactory image was 10% median.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1620888 TI - Influence of shielding blocks on the output of photon beams as a function of energy and type of treatment unit. AB - The influence of field-defining shielding blocks on the output of a cobalt unit and of seven different accelerators (one with dual energy output) has been investigated. The quality indices range from 0.57 (cobalt-60) to 0.79. The loss in output due to shielding blocks has been calculated taking into account loss in phantom scatter only. Comparison with experimental results shows that the calculation algorithm is correct in most of the clinical conditions. However, for quality indices of 0.70 and higher, for blocks close to the central beam axis, an overestimation of the output by the algorithm has been found. The maximum deviation observed is about 5% for the highest energy and for block positions corresponding to those applied, e.g. for inverted Y-fields with narrow lumbo aortic block spacing. PMID- 1620889 TI - Additive effects of cisplatin and radiation in human tumor cells under oxic conditions. AB - The interaction of cisplatin and irradiation was studied in vitro in four human cell lines. Additive effects were observed for the combination given either simultaneously or sequentially. No influence on recovery was seen in split-dose experiments. It is concluded that radiosensitization cannot be presumed in every clinical setting of combined treatment with radiation and cisplatin. PMID- 1620890 TI - [Stereotaxic surgery in Parkinson's disease. A preliminary report of 2 cases]. AB - Two patients presenting Parkinson's disease underwent thalamotomy by a stereotactic procedure at San Fernando Clinic. These patients were selected using a strict protocol. The surgical procedures and the results have been described. Review of potential complications are also discussed. Thalamotomy by stereotactic surgery is a method that offer excellent results in patients presenting movement disorders. Specifically in Parkinson's disease, it has demonstrated a great effectiveness in abolishing tremor and in controlling hypertonia. Bradykinesia does not seem to respond to this procedure. PMID- 1620891 TI - [The coexistence of the intermetamorphosis and Foley syndromes: an interhemispheric disconnection or a limbic hyperconnection?]. AB - The case of a patient with both, the intermetamorphosis and the Foley syndromes is studied. Both of these syndromes are extremely infrequent and their coexistence in a single patient points up to a common etiopathogenic mechanism. The relevant literature is discussed and a limbic hyperconnection syndrome is proposed to explain the clinical findings as well as the positive response to valproic acid. PMID- 1620892 TI - [A preliminary report on penile cancer in the Instituto Oncologico Nacional from 1982 to 1990]. AB - Cancer of the penis is not to common disease and its incidence varies between 0.5 and 5%. In Panama, 70 cases were registered from 1982 to 1990 and it is considered an important social problem in the rural population. Phimosis and poor hygiene are important factors in its etiology. Of 70 cases seen at the National Institute of Oncology from 1982 to 1990, 51 cases were analyzed comparing two approaches in regard to lymph node metastasis: (1) an expectant approach in those without clinically suspected lymph node metastasis, and (2) lymph node biopsy using the Cabanas technique in those clinically suspected followed by lymphadenectomy if the biopsy was positive. The high percentage biopsies (Cabanas technique) as well as the significant morbidity (31.6%) in these patients, compared with no morbidity and the high accuracy of the expectant approach (90%) lead the authors to recommend the Cabanas biopsy technique only for patients of low educational level and difficult follow-up as outpatients. Others patients should be followed clinically for signs of tumor activity. PMID- 1620893 TI - [Single craniotomy by trephining and closed-circuit external drainage for the treatment of chronic subdural hematoma]. AB - Chronic subdural hematoma is one of the most frequent pathological entities in the adult. Therapeutic approaches have ranged from craniotomy with excision of the membrane to close external drainage placed, under local anesthesia, at the bedside. The authors report the results of treatment of twelve (12) patients by craniotomy with placement of a closed external drainage for the gradual emptying of the chronic subdural hematoma. PMID- 1620894 TI - [A leiomyosarcoma of vascular origin. A case report]. AB - Leiomyosarcomas arising from the wall of the blood vessels, are highly malignant tumours. Although 75% of the cases have been reported in the inferior vena cava, nevertheless scanty mention is made in the literature of an analogous tumor originating from smaller blood vessels. This paper deals with a 53-year-old man with a tumor in the right axilla. Surgery consisted in wide local excision. Histopathology revealed a mesenchymal tumor in an axillary blood vessel. Electron microscopy revealed tumor cell with all the characteristics of a leiomyosarcoma. The patient refused adjuvant therapy and died 10 months later with local recurrence and lung metastases. PMID- 1620895 TI - [An ectopic ureter which drained into the perianal area]. AB - The author reviews the clinical record of a 6-year-old boy, who had urinary incontinence with wetting of his underwear in the posterior part. IVP, Cystoscopy, Cystogram, Left Retrograde Pyelogram and Surgery showed a double distal ureter on the left side. The normal ureter drained in the bladder in the orthotopic ureteral orifice. The medial dilated ectopic ureter, in the form of an H, was connected to the normal ureter and drained in the perianal area. The incontinence stopped after the resection of the ectopic ureter. PMID- 1620897 TI - [The Earl Silas Tupper Research and Conference Center]. PMID- 1620896 TI - [The cholera epidemic in Panama 1991]. AB - The authors studied the epidemiology of the outbreak of cholera (due to Vibrio cholerae 01, Inabe serotype) which occurred in Panama in 1991, during which 1179 probable cases were reported, with 292 hospitalizations, 29 deaths and 51 confirmed cases. There was an average of 24.7% hospitalizations and a 2.5% mortality. The epidemic involved 21 of 24 "corregimientos' in Darien, 2 of 4 in San Blas, 5 of 15 in Panama East, 3 of 40 in Colon and one of 19 in the metropolitan area of Panama City. The incidence of infected patients was seen in infants less than 1 year old and in children 1 to 4 years of age. Taking into account the population in each 'corregimiento', it can be said that less than 1% of the population was infected, but that in San Blas, where few communities have aqueduct and latrines, 10% of the population was infected. PMID- 1620898 TI - [Intestinal perforation by Angiostrongylus costaricensis. A report of 2 cases]. AB - Two cases of abdominal angiostronylosis with terminal ileum perforation are reported. The first two cases diagnosed in Panama of a well established eosinophilic granulomatous process which affects mostly children in Costa Rica. The parasite Angiostrongylus costaricensis has been demonstrated in cases with a geographic range, from Mexico down to Brazil. The parasite has been found in rodents in Panama (Sigmodon hispidus and Rattus rattus) with an still pending further epidemiological and serological studies in order to determine the true disease morbidity. PMID- 1620899 TI - [The premenstrual tension syndrome. The role of molimina]. AB - The author reviews the premenstrual syndrome, from its aetiological and physiopathological characteristics, as well as considerations in regards to its clinical manifestation and therapeutical possibilities. The concept of "molimina" and its hormonal characteristic is defined, as well as its manifestations within the PMS. PMID- 1620900 TI - [Creutzfeldt-Jakob disease. The first case with histopathological study in Panama]. AB - We studied the clinical and histopathology findings of the first proved case of Creutzfeldt-Jakob disease in Panama. A sixty-five-years-old female patient referred from Santiago de Veraguas was admitted to Santo Tomas Hospital with a progressive clinical picture of dementia, incoordination and generalized myoclonia. The electroencephalogram showed periodic paroxysmal activity. The patient died eight months after initiated the disease. The cerebral histopathologic study was characteristic of Creutzfeldt-Jakob disease: status spongiform, neuronal loss and non-inflammatory gliosis was found. PMID- 1620902 TI - Vascular factors in bronchial hyperresponsiveness and asthma. PMID- 1620901 TI - [Urethral lengthening with a tube flap (Kropp's operation) and gastrocystoplasty]. AB - Gastrocystoplasty associated to a Kropp procedure in our experience has been an excellent alternative to improve the quality of life and renal function in patients with severe bladder dysfunction and urinary incontinence. Technically offers easy development of a gastrointestinal segment not requiring ureteral reimplantation or detubularization with the consequent excess of sutures required traditionally in these procedures. Also the postoperative care was smoother and shorter than previously using with the obvious advantage of less mucus production and no metabolic disturbances often present. Further catheterization might be performed through a physiological way obviating abdominal stomas. PMID- 1620903 TI - The abnormal oropharyngeal carrier state: symptom or disease? PMID- 1620904 TI - Emphysema revisited. PMID- 1620905 TI - Postoperative pulmonary function abnormalities after coronary artery bypass surgery. AB - In 18 patients, postoperative effects of coronary bypass surgery were evaluated. Pulmonary function studies were conducted preoperatively, and 1 and 6 weeks postoperatively, by means of spirometry, respiratory pressures, body plethysmography and impedance measurement of the respiratory system using the forced oscillation technique. One week postoperatively, total lung capacity (P less than 0.0001), inspiratory vital capacity (P less than 0.0001) forced expiratory volume (P less than 0.0001) and functional residual capacity (P less than 0.01) decreased significantly, while residual volume remained unchanged. This restrictive respiratory impairment was accompanied by significant decreases in inspiratory (P less than 0.0001) and expiratory (P less than 0.01) mouth pressures and significant decreases in respiratory resistance values (P less than 0.01). Six weeks postoperatively, significant differences in total lung capacity (P less than 0.0001), inspiratory vital capacity (P less than 0.0001) and forced expiratory volume (P less than 0.0001) persisted, while respiratory pressures returned to the preoperative values. It is concluded that respiratory muscle weakness contributes to the immediate postoperative restrictive lung function loss. Furthermore, structural alterations of chest wall mechanics have to be supposed for the persisting late restrictive pulmonary impairment. PMID- 1620906 TI - Utility of squamous cell carcinoma antigen (SCC Ag) as a tumour marker in pulmonary malignancy. AB - Squamous cell carcinoma antigen (SCC Ag), a recently developed tumour marker, has shown some promise, particularly in squamous cell carcinoma (SCC) of the uterine cervix. To evaluate its usefulness in SCC of the lung, serum SCC Ag levels were measured in 52 patients with a variety of respiratory diseases (both benign and malignant), 17 patients with renal failure and 56 healthy controls. SCC Ag was elevated in 11 of 25 patients with SCC lung and one patient with a mixed adeno squamous tumour, but in no patients with other malignancies or benign respiratory disease. SCC Ag levels appeared unrelated to either tumour stage or the degree of differentiation. False-positive results were noted in patients with renal failure, with six of eight patients with a plasma creatinine greater than 0.7 mmol l-1 having an elevated SCC Ag level. Because SCC Ag was highly specific in the presence of normal renal function, an elevated level would support early investigation of a patient with suspected pulmonary malignancy. The potential of SCC Ag in typing large cell lung carcinomas (where light microscopic features of SCC are uncertain) warrants further investigation. PMID- 1620907 TI - Postoperative chest infection after upper abdominal surgery: an important problem for smokers. AB - The incidence and risk factors for postoperative chest infection have been studied in 127 patients undergoing elective upper abdominal surgery. The overall incidence of postoperative chest infection was 20.5%. Mean length of postoperative stay was extended from 7.8 to 10.7 days in those developing infection (P less than 0.05). Patients who smoked cigarettes and those with smoking related diseases had a considerably higher risk of infection. Patients with chronic bronchitis and airflow obstruction had an incidence of infection of 85.7%, those with chronic bronchitis alone 83.3% and those with airflow obstruction and no chronic bronchitis 50%. Patients with a smoking history of greater than or equal to 20 pack years but no chronic bronchitis or airflow obstruction had an incidence of 20.8%. All three were independently significant risk factors for infection. Patients without respiratory disease and who were non smokers had an incidence of infection of only 7.1%. Smoking and its sequelae are the principal risk factors for postoperative chest infection. This study shows that the high risk patient can readily be identified by enquiry into respiratory symptoms, smoking history and by spirometry. This is the group in whom prophylactic measures are especially important, and they require close supervision to enable early identification and therapy of infection. PMID- 1620908 TI - Effects of pulmonary function of oral high frequency oscillation in normal and asthmatic subjects. AB - High frequency jet devices are not only used as 'internal percussors' to aid clearance of pulmonary secretions, but are also a mode of ventilatory support. As physical stimuli can cause bronchospasm in asthmatic individuals, we hypothesized that direct airway vibration may induce bronchospasm. To ascertain whether an airway vibration jet device could cause bronchoconstriction, we exposed eight asthmatic and six normal subjects to 5 min of jet-induced airway vibration or placebo treatment with cross-over at 3 h. Subjects breathed spontaneously for 5 min through an open mouthpiece into which either jet (10 Hz, 25 psi) or sham pulsations (same device, pressure vented to room at compressor) were delivered in a double-blind, random order. A constant-volume body plethysmography measured functional residual capacity and specific airway conductance (SGAW) and a water seal spirometer measured forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). These pulmonary function measurements were taken before and at 5, 10, 20, 30, 60, 90 and 120 min after each exposure. In the normal subjects there was no significant change in any pulmonary function. There was not statistically significant change in the pulmonary function in the asthmatic patients. However, the oral high frequency oscillator induced a clinical asthmatic attack in one asthmatic patient. In this one patient, the FEV1 fell 35% from its initial value at 5 min following exposure to a maximum of 49% decline from initial value at 1 h following exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1620909 TI - The role of inexperience in measuring tuberculin skin reaction (Mantoux test) by the pen or palpation technique. AB - We have shown previously that experienced readers can use the palpation or pen method for reading the Mantoux tuberculin skin test with accuracy. In order to investigate if the inexperienced reader can use both methods with the same degree of accuracy, we performed Mantoux tests in 539 healthy subjects, aged 20-57 years (mean 33 years), using the PPD-RT 23 in dose 2 I.U. (1/5000). In random order and a double-blind fashion, an experienced and an inexperienced reader measured the induration after 48 h by the palpation method initially and then by the pen method, without knowing the identity of the subject. Results of the study did not show any significant difference in any range of measurements by the two readers, using either the pen or palpation method (P greater than 0.1). A highly statistically significant linear relationship was found between the measurements by the pen method used by experienced and inexperienced readers (r = 0.823, P less than 0.0001) and between the palpation measurements by the two readers (r = 0.939, P less than 0.0001). We conclude that the effects of an inexperienced examiner in the measurement of of tuberculin skin induration are minimal. Inexperienced readers can use the pen method as accurately as the traditional palpation method. PMID- 1620910 TI - An investigation of the relationship between microbial and particulate indoor air pollution and the sick building syndrome. AB - The sick building syndrome has been the subject of research for approximately 10 years. Although it is often suggested that symptoms in office workers are due to circulating micro-organisms or particles, epidemiological studies investigating the relationship between them have been lacking. This cross-sectional study has combined medical and aerobiological assessments of offices in Great Britain and has found that, although airborne particulates and micro-organisms are unlikely to be the sole cause of the sick building syndrome, positive associations between symptom prevalence rates and levels of airborne viable bacteria and fungi within groups of buildings with similar ventilation systems, suggest a possible causal link that should be explored. PMID- 1620911 TI - A clinically relevant modification to existing inhaler therapy. AB - A modified formulation of inhaled salbutamol and a new inhaler device were studied in a group of 11 moderate-to-severe asthmatic patients. Changes in airway calibre (FEV1, Vmax30) were measured before and after inhalation of the new formulation, and compared with changes following inhalation of conventional salbutamol. A standard Rotahaler was used as a reference for the new inhaler. The study was conducted as a two-part randomized, double-blind cross-over trial. We found a significantly greater bronchodilatation of the larger airways using the modified drug in the Rotahaler. The new inhaler did not show any superiority over the Rotahaler, contrary to expectations from in vitro work. A slightly shorter model may better reflect the in vitro results. The study has implications for inhalation therapy in general. PMID- 1620912 TI - The value of bronchoalveolar lavage and bronchial washings in the diagnosis of invasive pulmonary aspergillosis. AB - The objective of this study was to clarify conflicting reports of the sensitivity and specificity of bronchoalveolar lavage or bronchial washings for diagnosing invasive pulmonary aspergillosis. The study was a retrospective review of 300 consecutive patients in a tertiary referral centre subjected to 343 fiberoptic bronchoscopic procedures for the evaluation of pulmonary infiltrates. Classification of paired fungal culture and cytologic examination of bronchoalveolar lavage or bronchial washing fluid according to clinical, radiographic, histological and autopsy evidence of invasive pulmonary aspergillosis. One-hundred and fifteen deaths occurred, with a 58% autopsy rate. A diagnosis of invasive pulmonary aspergillosis was made in 21 immunosuppressed patients with 16 deaths. Bronchoalveolar lavage cytology showed aspergillus in 19 specimens (invasive pulmonary aspergillosis in 16), cultures yielded aspergillus in 41 (invasive pulmonary aspergillosis in ten), with both tests positive in nine. Cytology sensitivity was 64.0%, specificity 99.1%, positive predictive value 84.2%, and negative predictive value 97.2%. Culture sensitivity was 40.0%, specificity 90.3%, positive predictive value 24.4%, and negative predictive value 95.0%. Concordant cytology and culture sensitivity was 32.0%, specificity 99.7%, positive predictive value 88.9%, and negative predictive value 94.9%. In conclusion, when characteristic hyphae are visualized in bronchoalveolar lavage specimens from immunosuppressed patients with compatible clinical data, it is advisable to treat for presumptive invasive pulmonary aspergillosis. PMID- 1620913 TI - Necrotizing fasciitis: is it a fatal complication of tube thoracostomy?--Report of three cases. PMID- 1620914 TI - Low carbon monoxide transfer factor (TLCO) in HIV-infected patients without lung disease. PMID- 1620915 TI - The use of thermography in clubbing. PMID- 1620916 TI - Assessment of portable oxygen therapy. PMID- 1620917 TI - [Advances in the diagnosis of digestive diseases]. PMID- 1620918 TI - [Value of the determination of CA 15-3 in the diagnosis of malignant pleural effusion]. AB - In 160 consecutive patients with pleural shedding, antigen CA 15-3 values in pleural fluid were determined, in a prospective way using monoclonal antibodies (115D8 and DF3). In 49 patients with malignant pleural shedding, the mean value of CA 15-3 (47.6 U/ml) was significantly higher (p less than 0.01) to the values in the 111 benign ones (12.9 U/ml). Its sensibility for malignity, with a trough level of 27 U/ml, was of 37% with an specificity of 96%. When a specificity of 100% was required its sensibility (18%) was significantly lower to the carcinoembryonic antigen (CEA) (33%), measured simultaneously with comparative purposes. The simultaneous determination of both markers raised sensibility to 39%, without reaching statistical signification. In the ten patients whose pleural sheddings was secondary to breast carcinoma, both minimum (15 U/ml) as medium (110 U/ml) values, as well as CA 15-3 sensibility (80%), were higher to the ones found in the rest of patients with shedding of malignant origin, but without a clear superiority over the values obtained with CEA. Based on these results, we conclude that the usefulness of the determination, as a tumoral marker, in pleural fluid, of CA 15-3 is lower than CEA and that its simultaneous determination seems not justified. We think that its specific usefulness in pleural sheddings secondaries to breast carcinomas deserves a study with a bigger sample. PMID- 1620919 TI - [Long-term results of endoscopic sphincterotomy in the treatment of residual/recurrent choledocholithiasis]. AB - Endoscopic sphincterotomy is widely accepted as the technique of choice in the treatment of residual or recidivant choledocholithiasis since the results obtained with this technique are favorable when compared to biliary surgery in most series. However, the experience of long term follow up of patients with choledocholithiasis in whom this technique would have been applied as the only treatment is still scarce up to date. We have studied 40 patients (mean age 65.6 +/- 11.1 years) with residual or recidivant choledocholithiasis who had undergone endoscopic treatment successfully before the 30th of June 1985, who could be contacted by a mailed questionnaire or by phone by August 1990. The follow up time 70.7 +/- 19.4 months (mean +/- typical deviation). Out of them, 36 (90%) had been asymptomatic up to the contact date (30 cases) or up to death due to causes not related to biliary pathology (6 patients). Out of the 4 remaining patients, 2 presented mild dyspepsia and another patient has probably developed recidivant choledocholithiasis (according to I.V. cholangiography). The fourth patient presented a severe episode of cholangitis and acute pancreatitis, related to a new episode of choledocholithiasis and died 5 and a half years after the endoscopic sphincterectomy. This represents a 2.5% mortality. These long term results of endoscopic sphincterotomy in patients with residual or recidivant choledocholithiasis are an other point in favour of using this technique as the single treatment of choice in patients above 60 years old. PMID- 1620920 TI - [Antibodies against mycobacterial antigens in patients with non-tuberculous pathology]. AB - Antibodies (type IgG) against the A 60 antigen (Mycobacterium bovis, BCG) and an antigen of Mycobacterium tuberculosis were studied by ELISA in 79 patients with not tuberculous disease: 16 lung carcinoma, 16 hepatic cirrhosis and 47 patients with pulmonary disease. 59.5% and 50.6% of the patients showed antibodies against antigen A 60 and M. tuberculosis antigen respectively; more 25% were strongly positive against antigen A 60; in the patients with lung carcinoma this results were 62.5%. It is concluded than when this methods are use in the serologic diagnostic of tuberculosis the number of cirrhotic and not tuberculous pulmonary disease patients with antibodies against this antigens, obliges a careful study of the individual characteristics of each patient, and it is very important previously to discard a lung neoplastic pathology. PMID- 1620921 TI - [Antiphospholipid antibodies and cerebral infarction]. AB - The antiphospholipid antibodies syndrome is clinically characterized by the presence of thrombosis, repetitive abortions and/or thrombopenia. During the past years, thanks to the development of techniques for its detection, its relationship with cerebrovascular accidents has become of special interest. Two patients with antiphospholipid antibodies and multiple cerebral infarcts are presented and the clinical and pathogenic aspects of this association are reviewed. PMID- 1620922 TI - [Bochdalek hernia with gastric incarceration and volvulus]. AB - Bochdalek's hernia is infrequent in adults. We communicate the case of a 22 year old male that was admitted at hospital because of a thoracic pain of sudden onset. In the exploration there was pain in left hypochondrium non tolerating decubitus. Thorax radiology showed an "arched" image in left pulmonary base and pleural shedding. The patient underwent a surgical procedure in which a great gastric herniation was found, which forced a total gastrectomy. PMID- 1620923 TI - [Squamous cell carcinoma of the tongue and HIV infection]. AB - It is reported the case of a 39 year old male, non homosexual, seropositive to HIV due to polytransfusion, without AIDS diagnostic criteria and with a severe depression in cellular immunity, expressed as lowering in CD4+ T cells, and in the CD4+/CD8+ ratio, who showed, without having any risk-factors, a squamous cell carcinoma of the tongue. We review the cases reported in the scientific literature on the association between squamous-cell carcinoma and AIDS or HIV infection. PMID- 1620924 TI - [Periodic health examination]. AB - A literature search has been made on the examinations to be performed during the "periodic health exam" on the healthy adult. These examinations shall be performed bearing in mind the prevalence and morbility data of the specific diseases, individual risk factors and the quality (sensibility and specificity) of the diagnostic procedure. The value of regular blood pressure determination, breast exam and cervical cytology with Papanicolaou stain, is well established. However, there is no consensus regarding other determinations, due to the fact that different authors use different approaches. The skin, mouth and thyroid examination for cancer screening is limited only to individuals having risk factors. Heart auscultation for the diagnosis of valvulopathies that could required antibiotic prophylaxis for bacterial endocarditis is important. In individuals over sixty years old, vision acuity and hearing capabilities should be explored, also abdomen should be explored to detect aortic aneurysms. Hypercholesterolemia should be determined in individuals over 20 years old, and PPD should be performed before 35 years old. Concerning the rest of explorations (rectal taction, testicular exploration, etc.) its efficacy has not been clearly established in the screening. PMID- 1620925 TI - [New gamut: cavitated pulmonary nodules and localized deformity of the cardiac region]. PMID- 1620926 TI - [Acute pancreatitis of biliary origin]. PMID- 1620927 TI - [Cryptococcal meningitis in patients with AIDS: combined treatment with amphotericin B and fluconazole, and high levels of adenosine deaminase in cerebrospinal fluid]. PMID- 1620928 TI - [Lethal meningitis caused by varicella-zoster virus in a patient with AIDS]. PMID- 1620929 TI - [Determination of anti-HIV antibodies at the autopsy table]. PMID- 1620930 TI - [Pulmonary cavity caused by Pneumocystis carinii in an HIV+ patient]. PMID- 1620931 TI - [Thymic carcinoma: report of a case]. PMID- 1620932 TI - [Lemierre syndrome--post-angina sepsis]. PMID- 1620933 TI - [Recurrent alveolar infiltrates: a form of radiologic spontaneous clinical course of bronchiolitis obliterans]. PMID- 1620934 TI - [Brucellosis with pleural involvement]. PMID- 1620935 TI - [Familial mediterranean fever or the need for an early diagnosis]. PMID- 1620936 TI - [Chyluria and lymphangioleiomyomatosis]. PMID- 1620937 TI - [Cutaneous epithelial necrosis in a patient in coma]. PMID- 1620938 TI - [Octreotide: clinical experience]. PMID- 1620939 TI - [1991. The year of PET?]. PMID- 1620940 TI - [A clinical study of human leptospirosis. Apropos 215 cases]. AB - 215 cases diagnosed of human leptospirosis in the Camaguey Province, Cuba, are studied, for the period between 1986 and 1990. The clinical and epidemiological features are studied, together with the anatomopathological study of the decreased. The most frequent complications and the treatment employed, including prophylactic measures, are analyzed. It is concluded that the disease is more frequent in young males, from a rural origin and with a farming job. Acute kidney failure was the main complication, and as for the therapeutic approach, penicillin was the antibiotic of election, prophylactic measures are important, specifically vaccination. PMID- 1620941 TI - [Kufs' disease. A review of the literature apropos a case]. PMID- 1620942 TI - [Intraoperative echography as an aid in the therapy of Caroli's disease. A case report]. AB - Congenital polycystic dilatation of the intrahepatic biliary ways (Caroli's disease) is a rare disease. The "pure" type and the one associated with congenital hepatic fibrosis are accepted. Although the current exploration methods, its diagnosis is rare before the surgical procedure. Treatment of the diffuse pure types and the ones associated with hepatic fibrosis is difficult and the outcome is bad. A case of the less frequent type is communicated, in which, as a novelty, intrasurgical echography was used in its treatment. PMID- 1620943 TI - [Carney's triad: a short review apropos a case]. AB - We communicate a case with the Carney triad (gastric leiomyosarcoma, pulmonary chondromatosis and extra-adrenal paraganglioma). It is, to our knowledge, the first case to be communicated in the Spanish scientific literature. We discuss some peculiar aspects of the debut and clinical evolution of this syndrome, together with its prognosis. We conclude that in clinical practice, the appearance in a young subject, specifically females, of multiple gastric myogenic tumors, should elicit the performance of further noninvasive procedures, needed to discard the diagnosis of the Carney triad. PMID- 1620945 TI - [A man of 68 with infectious endocarditis who died suddenly]. PMID- 1620944 TI - [An obstruction of a valve prosthesis implanted in the tricuspid position]. AB - Dysfunction of a prosthesis implanted in tricuspid position is a severe complication that may develop with minimal symptoms. A patient who presented clinical manifestations of heart failure for two weeks due to obstruction of a mechanical prosthesis in tricuspid position is described. Fibrinolytic treatment was given unsuccessfully, therefore prosthetic replacement was performed. In the removed prosthesis, a fibrotic pannus which developed in the strut and disc was seen. We review the clinical manifestations, the diagnosis and treatment of the dysfunction of a prosthesis implanted in tricuspid position. PMID- 1620946 TI - [Prognostic factors in HIV-infected heroin addicts: a multivariate analysis of nonspecific serological factors in the evolution of the infection]. AB - We present a prognostic analysis of the quantifying of serum levels of beta 2 microglobulin, neopterina, IL-2 soluble receptor and three major classes of immunoglobulins, in a group of 68 heroin-addicts infected by the human immune deficiency virus, type I, clinically assessed for a period of at least three years. High levels of any of these unspecific serologic factors were correlated with the illness progression. Survival curves were generated with the categorized variables, showed a significant decrease on the time interval prior to the diagnosis of AIDS, in the patients with these variables assigned on the higher groups, being neopterine and IgA the more predictive factors when the Cox proportional regression model is applied. We conclude that the quantifying of these unspecific serum factors provides a useful information regarding the clinical evolution of heroin-addicts with HIV infection. PMID- 1620947 TI - [A fever syndrome of long evolution as the first manifestation of secondary syphilis]. PMID- 1620948 TI - [Leukocytoclastic vasculitis and acute cardiorespiratory insufficiency]. PMID- 1620949 TI - [Spontaneous rupture of the spleen in infectious mononucleosis]. PMID- 1620950 TI - [Listeria monocytogenes: the cause of cholangitis in a liver transplant?]. PMID- 1620951 TI - [A cerebral infarct as the initial manifestation of hypertrophic cardiomyopathy in a young patient]. PMID- 1620952 TI - [An idiopathic segmental infarct of the greater omentum: a new case with massive hemoperitoneum]. PMID- 1620953 TI - [Marchiafava-Bignami disease with a favorable clinical evolution]. PMID- 1620954 TI - [Hypophyseal apoplexy simulating a parasellar aneurysm]. PMID- 1620955 TI - [Temporal arteritis with involvement of the subclavian arteries]. PMID- 1620956 TI - [Mixed community-acquired pneumonia due to anaerobic bacteria]. PMID- 1620957 TI - [An intracranial epidural abscess]. PMID- 1620958 TI - The effect of experimental infection with Corynebacterium pseudotuberculosis on reproduction in adult ewes. AB - Fifteen ewes were inoculated subcutaneously with 2 x 10(6) cells of Corynebacterium pseudotuberculosis seven days before mating, during the embryonic stage of gestation and during the fetal stage of gestation. The clinical signs, antibody response and the consequences of the infection on reproduction were studied. None of the ewes showed any change in general condition during pregnancy. The effects of experimental infection during gestation were evident after incubation periods that ranged from 25 to 140 days after inoculation and were dependent on the time of the inoculation in relation to the period of gestation. Ewes inoculated before gestation can resolve infection. Ewes inoculated during the embryonic stage were severely affected and some aborted. In others lambs were stillborn or, if born alive, infected. Ewes inoculated during the fetal stage of gestation did not show reproductive disorders although some remained chronically infected. PMID- 1620959 TI - Bioassay of bovine interleukin-1-like activity. AB - A bioassay for bovine interleukin-1 (IL1) activity is described. The assay is based on the IL1-stimulated proliferation of a mouse T-lymphocyte cell line, D10(N4)M. Bovine mononuclear cells stimulated with lipopolysaccharide produce an interleukin-1-like activity which stimulated the growth of the D10(N4)M cell line in a dose-dependent manner. The stimulatory activity was neutralised by a combination of both anti-human IL1 alpha and anti-human IL1 beta sera. The quantity of IL1-like activity released from the mononuclear cells increased asymptotically with increasing lipopolysaccharide dose. PMID- 1620960 TI - Aetiopathogenesis of canine elbow osteochondrosis: a study of loose fragments removed at arthrotomy. AB - Twenty-five ununited coronoid processes (UCP) and 24 osteochondritis dissecans (OD) flaps were examined by light and transmission electron microscopy. Chondrocytes showed degenerative changes but remained viable and continued to secrete matrix components, even though the organisation of the matrix was altered. Differences in the histological and ultrastructural appearance of the two lesions tend to suggest that they are two separate disease entities, although they may occur together in the same joint. It is hypothesised that OD results from incorrect cartilage maturation and endochondral ossification. The aetiology of UCP is unclear but there is a possibility of its being a subchondral fracture, with an ineffective fibrous repair in some cases. PMID- 1620961 TI - Comparative studies on N'Dama and zebu cattle following repeated infections with Trypanosoma congolense. AB - Twenty N'Dama and eight zebu cattle were inoculated intradermally with bloodstream forms of a cloned strain of Trypanosoma congolense originating from East Africa. All inoculated cattle became parasitaemic. Zebus showed consistently higher levels of parasitaemia and lower packed red cell volume (PCV) percentages than did N'Damas. Three of the eight zebus required treatment when high numbers of trypanosomes were present in the blood and PCV values dropped below 15 per cent. None of the N'Dama cattle needed treatment. Statistical analysis was performed on the data to assess the variability of parasitaemia and PCV levels before and during infection of the N'Dama cattle. The variation in PCV values was large between individuals during the early stages of the disease and diminished as infection continued. After trypanocidal drug treatment and a recovery period of 14 months, the same animals were inoculated intradermally with T congolense bloodstream forms isolated and cloned in The Gambia. Differences in susceptibility to the ensuing disease were apparent when comparing N'Dama and zebu cattle. Five zebu cattle needed trypanocidal drug treatment, while none of the N'Damas needed drug intervention. Ranking the 20 infected N'Damas according to average PCV levels revealed that the animals responded similarly to both infections. PMID- 1620962 TI - Comparison of the pathogenicity for pregnant sheep of Rift Valley fever virus and a live attenuated vaccine. AB - A live attenuated mutant of Rift Valley fever virus, MV P12, was previously shown to be non-pathogenic in young lambs, but capable of producing protective immunity. The studies reported here show that the abortion in sheep caused by an infection with virulent virus is the result of necrosis of the maternal villi and cotyledons arising from an acute inflammation of the maternal caruncles. Pregnant ewes infected with the attenuated mutant virus MV P12 showed none of these lesions in the placenta and gave birth to healthy lambs. Colostrum from ewes infected with MV P12 virus was able to induce protective immunity in the offspring. These data along with previously published results suggest that the mutant virus MV P12 is an excellent candidate for use as a live attenuated veterinary vaccine. PMID- 1620963 TI - Epidermal and hepatic glucocorticoid receptors in cats and dogs. AB - Low capacity, high affinity [3H] dexamethasone binding receptors were identified in cytosolic preparations of liver (mean number 45 +/- 10.1 fmol mg-1 protein, apparent dissociation constant 0.4 +/- 0.1 nM) and skin (mean number 46.4 +/- 23.8 fmol mg-1 protein, apparent dissociation constant 1 +/- 0.2 nM) of clinically normal dogs. For clinically normal cats, approximately half these numbers of receptors with a lower affinity, were detected in liver (mean number 23.1 +/- 10.4 fmol mg-1 protein, apparent dissociation constant 3.2 +/- 0.9 nM) and skin (mean number 23.90 +/- 10.9 fmol mg-1 protein, apparent dissociation constant 2.2 +/- 1.5 nM). This difference between dogs and cats in [3H] dexamethasone binding receptors may contribute to the relative glucocorticoid resistance observed in cats. PMID- 1620964 TI - Cardiovascular response to acute hypoxia in double-muscled calves. AB - Hypoxic-induced pulmonary hypertension is known to be intensive in the bovine species and sometimes leads to pathological cardiac repercussions. On the other hand, doubled-muscled cattle are predisposed to develop hypoxaemia during exercise and with respiratory diseases. Therefore the purpose of this study was to investigate the cardiovascular response to acute hypoxia in double-muscled calves compared with calves of standard conformation. Pulmonary arterial pressure, electrocardiogram and blood temperature were simultaneously recorded, arterial blood was sampled for blood gas analysis and cardiac output was determined in six Friesian calves and six double-muscled calves of the Belgian White and Blue breed(BWB) when breathing air (fractional inspiratory oxygen concentration [FIO2]: 21 per cent) and when breathing a hypoxic gas mixture (FIO2: 10 per cent). All the absolute values of the measured parameters were significantly (P less than or equal to 0.001) different between the two breeds, except heart rate and arterial blood gas values. The pattern of hypoxic-induced decrease in arterial PO2 was similar in the two breeds of calves, suggesting that the pulmonary exchange capacities during hypoxia are no less efficient in double muscled calves than in calves of standard conformation. Similarly, the percentage of variation of the mean pulmonary arterial pressure from its normoxic to its hypoxic value was the same in the two breeds of calves, suggesting that double muscled calves are not predisposed to develop a more precocious or more intense pulmonary hypertension for a given level of hypoxaemia. The significantly smaller normoxic and hypoxic cardiac index and stroke index found in BWB compared with Friesian calves was interpreted as a less efficient cardiac function in double muscled subjects. PMID- 1620965 TI - Bovine spongiform encephalopathy: case-control studies of calf feeding practices and meat and bonemeal inclusion in proprietary concentrates. AB - Following the identification of meat and bonemeal as the most likely source of exposure for the occurrence of bovine spongiform encephalopathy (BSE) in Great Britain case-control studies were initiated to investigate this hypothesis. These involved a comparison of the consumption of specific proprietary calf feedstuffs, and whether or not meat and bonemeal had been included, between animals born in 1983-84 in BSE-unaffected herds and confirmed cases of BSE also born in 1983-84. The feeding of proprietary concentrates containing meat and bonemeal was found to be a statistically significant risk factor for the occurrence of BSE. These studies therefore support the initial hypothesis that BSE occurred as a result of exposure to a scrapie-like agent via meat and bonemeal. PMID- 1620966 TI - Bovine spongiform encephalopathy: detection of fibrils in the central nervous system is not affected by autolysis. AB - The effect of autolysis on the electron microscopic detection of the characteristic abnormal fibrils, originally called 'scrapie-associated fibrils', was investigated in four different areas of the central nervous system (CNS) from 10 clinically suspect BSE cattle after post mortem delay and compared with the histopathological diagnosis. The tissues for fibril detection were subjected to controlled incubations to simulate autolysis. Fibril detection in all areas sampled from nine animals in which BSE was confirmed by histopathology was not affected by combined post mortem delays and specific controlled treatments. Detection of fibrils from the cervical spinal cord was no less sensitive than from brain areas. Fibrils were not detected in the one suspect case in which histopathology did not reveal lesions of BSE. The study confirms that fibril detection is of diagnostic value in BSE when post mortem autolysis renders CNS material unsuitable for histopathology. PMID- 1620967 TI - Effect of pantothenic acid on disposition kinetics and tissue residues of sulphadimidine in chickens. AB - Sulphadimidine was administered to chickens via the intracrop route to determine plasma concentrations of the unchanged sulphonamide and its acetylated derivatives, kinetic disposition, tissue residues and acetylation. The sulphadimidine was given alone (group 1) at a dose of 200 mg kg-1 bodyweight. Pantothenic acid was given via the intracrop route at a dose of 100 mg kg-1 bodyweight one hour before (group 2) and six hours after (group 3) sulphadimidine administration (200 mg kg-1 bodyweight intracrop). The highest plasma concentrations of sulphadimidine in groups 1, 2 and 3 were reached in 1.73, 1.62 and 1.71 hours, respectively, following intracrop administration. In birds of groups 1, 2 and 3 no sulphadimidine was detected at 72, 24 and 48 hours, respectively, following its administration. Estimation of sulphadimidine in most of the body tissues revealed that all tissues examined had lower concentrations than plasma. In chickens given pantothenic acid (groups 2 and 3) before and after sulphadimidine administration, an increase in the concentration of N4 acetylated derivatives of sulphadimidine was observed compared with birds given sulphadimidine alone (group 1). PMID- 1620968 TI - Interleukin-1 stimulation of equine articular cells. AB - Prostaglandin E2 (PGE2) and stromelysin are produced by equine chondrocytes and synovial cells in vitro in response to recombinant human (rh) interleukin-1 (IL 1) alpha and beta, and equine mononuclear cell supernatants (MCS) containing IL 1. However, culture conditions are important. PGE2 concentrations increase in proportion to the concentration of fetal calf serum (FCS) in the culture medium, whereas stromelysin concentrations are inversely proportional to the concentration of FCS. Equine MCS, containing a lower concentration of IL-1 than the concentration of rhIL-1 used in these experiments, stimulated production of much higher levels of PGE2 than rhIL-1. In addition, equine MCS induced the production of broadly similar levels of PGE2 by both chondrocytes and synovial cells, whereas rhIL-1 was more active on equine synovial cells than equine chondrocytes. Although equine MCS induced both stromelysin and PGE2 production by equine articular cells, on the whole rhIL-1 failed to induce stromelysin production. This supports previous observations of species restrictions in the activity of human IL-1 on equine cells. Therefore, experiments using mammalian cells and heterologous IL-1 should be interpreted with caution. PMID- 1620969 TI - Cortisol binding capacity of corticosteroid binding globulin in hyperadrenocorticoid and healthy dogs. AB - Corticosteroid binding globulin (CBG) binding capacity and plasma cortisol concentration were determined in 27 dogs with hyperadrenocorticism and in 17 healthy control dogs. Cortisol concentrations were significantly higher in hyperadrenocorticoid dogs than in controls. CBG binding capacity did not differ between the two groups. It is concluded that excessive endogenous cortisol secretion does not induce an increase in CBG binding capacity. Consequently, the determination of CBG binding capacity provides no additional information for the diagnosis of canine Cushing's syndrome. PMID- 1620970 TI - Reciprocal translocation (13;20)(q12;q22) in an Icelandic sheep. AB - Cytogenetic examination of G-banded lymphocyte chromosomes of an Icelandic ram from a line with a history of poor fertility revealed a rcp (13;20) (q12;q22) translocation. Meiotic studies showed a quadrivalent configuration at diakinesis and this was confirmed by C-banding. PMID- 1620971 TI - Total venous inflow occlusion in the normothermic dog: a study of haemodynamic, metabolic and neurological consequences. AB - The acute haemodynamic and metabolic repercussions of total venous inflow occlusion were evaluated in six normal dogs, each of which underwent two four minute occlusions and one eight minute occlusion at normothermia. A further three dogs underwent a single eight minute period of occlusion and were allowed to recover from anaesthesia. Total venous inflow occlusion was well tolerated by all animals. They remained in sinus rhythm at the completion of occlusion, and unassisted haemodynamic recovery occurred rapidly. Recovery was quicker after four minutes than after eight minutes. There was no clinically detectable neurological impairment in three dogs which were allowed to recover. PMID- 1620972 TI - A new technique for surgery of the caudal vena cava in dogs using partial venous inflow occlusion. AB - The haemodynamic and metabolic effects of caudal vena cava occlusion were evaluated in six normal anaesthetised dogs. Each animal underwent a single eight minute episode of caudal vena cava occlusion. The procedure was well tolerated by all the dogs. Systolic arterial pressure was reduced by 62 +/- 5 per cent and the heart rate increased by 11 +/- 3 per cent. There was rapid haemodynamic recovery after the release of occlusion, all cardiovascular parameters returning to normal spontaneously within five minutes. Caudal vena cava occlusion is therefore safe for periods of up to eight minutes in normal dogs. This technique allows repair of caudal vena caval lesions without necessitating systemic heparinisation and the use of cavoatrial conduits. PMID- 1620973 TI - Effect of feed type on the pharmacokinetic disposition of oxfendazole in sheep. AB - The plasma concentration profiles of oxfendazole (OFZ), fenbendazole (FBZ) and FBZ sulphone (FBZ.SO2) were measured followed intraruminal administration of OFZ at 5 mg kg-1 to Merino weaners fed either dry forage or grazed on pasture lucerne clover. Plasma concentrations of OFZ and FBZ were significantly lower in sheep given the dry forage. PMID- 1620974 TI - A disc ELISA for the detection of Salmonella group D antibodies in poultry. AB - An ELISA using lipopolysaccharide antigens prepared from Salmonella gallinarum and S enteritidis was developed for the serological diagnosis of fowl typhoid and S enteritidis infection in poultry. There was good agreement between the results of the ELISA and conventional serological tests when samples from naturally infected birds and S enteritidis immunised birds were tested. Some cross reactions were observed when serum samples from S typhimurium infected birds were tested by ELISA. Subsequently a disc ELISA, using filter paper discs, was developed to facilitate sampling and testing of poultry. There was good correlation between the results of the disc and serum ELISAs and the test is recommended for the field testing of birds. PMID- 1620975 TI - Neuromata in docked lambs' tails. AB - Docked and undocked lambs tails obtained after slaughter were examined grossly and histopathologically. Stump and complex neuromata were identified in docked tails. PMID- 1620976 TI - Penetration of tinidazole into the gingival crevicular fluid in dogs. AB - Tinidazole was administered as a single oral dose of 15 mg kg-1 to 12 dogs, and its concentration in the plasma and gingival crevicular fluid (GCF) was measured at one and two hours by high performance liquid chromatography. Tinidazole was detectable in GCF in five dogs at one hour (6.8 +/- 2.6 micrograms ml-1) and in six dogs at two hours (9.2 +/- 1.4 micrograms ml-1) and in all plasma samples. In those animals with no detectable tinidazole in GCF, either the concentration of tinidazole in plasma was low or the volume of the GCF sample was insufficient for determination. The observed tinidazole levels in GCF exceeded the minimal inhibitory concentration values for most anaerobic oral bacteria. PMID- 1620977 TI - Effect of a M1-selective muscarinic receptor antagonist (pirenzepine) on basal bronchomotor tone in young women. AB - To examine the role of muscarinic M1-receptors in vagally mediated basal bronchomotor tone, we studied the effects of inhaled pirenzepine, which is a M1 receptor antagonist, on basal bronchomotor tone in 8 young women. To obtain dose response curves to inhaled pirenzepine, we measured partial and full flow-volume curves before and 30 min after inhalation of each concentration of pirenzepine (3.25-200 micrograms/ml). Maximum expiratory flow on partial flow-volume curve at 25% forced vital capacity (PEF25) was measured as an index showing basal bronchomotor tone. The dose-response curve of the percent increase in PEF25 by pirenzepine was biphasic in shape. PEF25 was significantly increased by 3.12 (14.5 +/- 5.8%), 6.25 (15.5 +/- 4.2%), 12.5 (20.0 +/- 0.29%) and 200 micrograms/ml (17.3 +/- 5.9%) of pirenzepine, but not by 25 (9.6 +/- 5.6%), 50 (9.4 +/- 6.2%) and 100 micrograms/ml (14.4 +/- 6.2%) of pirenzepine. The percent increase in PEF25 by 40 micrograms of ipratropium bromide was 66.2 +/- 14.2%. These results suggest that the role of M1-receptors in vagally mediated basal bronchomotor tone may be significant but little compared with M3-receptors in normal humans. PMID- 1620978 TI - Effect of histamine treatment on dopamine tachyphylaxis of canine tracheal smooth muscle. AB - In order to understand how histamine-sensitized airways may react to exogenous dopamine, we investigated the effect of histamine treatment on the dopamine induced contractions of canine tracheal smooth muscle. The results showed that preconstricting muscle strips with histamine (10(-6) M to 10(-4) M) not only increased the amplitude of dopamine-induced contraction, but also lowered the concentration of dopamine required to provoke contraction from 10(-4) M to 10(-6) M. In muscle strips desensitized by repeated challenges of 10(-3) M dopamine, a 15-min treatment with 10(-4) M histamine transiently restored the response. The restored contractions were decreased by the dopaminergic antagonist, domperidone, and the alpha 2-adrenoceptor antagonist, yohimbine, and increased by the beta 1 adrenoceptor antagonist, atenolol. It is concluded that in addition to its role in mediating airway constriction, histamine can promote and enhance the contractile response of canine tracheal smooth muscle to dopamine. Histamine treatment restored the dopamine response of desensitized tracheal muscle with resensitization of the adrenoceptors. PMID- 1620979 TI - Case report of desquamative interstitial pneumonia: documentation of preserved pulmonary function after twelve clinical relapses. AB - We describe a case of desquamative interstitial pneumonia diagnosed in a 25-year old woman who relapsed 12 times during a 20-year follow-up period. In each relapse, the involved sites were different and the patient ultimately recovered without resultant pulmonary ventilatory defects. Bronchoalveolar lavage performed during the 12th relapse revealed a remarkable increase in the number of total cells and showed a low CD4+/CD8+ ratio in the lymphocyte subset. PMID- 1620980 TI - Wegener's granulomatosis--treatment under revision? AB - A 44-year-old man with nasal and respiratory symptoms combined with positive serum antibodies to neutrophil cytoplasmic antigens (ANCA) suggestive of Wegener's granulomatosis was treated with antibacterial agents. Complete clinical response was achieved with co-trimoxazole, and the titer of ANCA declined. After a 12-month treatment period, the patient contracted fever and respiratory symptoms and fatigue again, and he had proteinuria and hematuria. After the institution of conventional treatment with oral prednisolone and cyclophosphamide, a favorable response was achieved. Wegener's-like granulomatosis is difficult to diagnose at its early stage, but the presence of ANCA may be helpful. We suggest that co-trimoxazole should be considered as a first-line treatment, under careful supervision, for young patients whose disease is limited to the respiratory organ. PMID- 1620981 TI - Leukemic pneumonitis as a poor prognostic factor in chronic myelomonocytic leukemia. AB - We report the case of a 69-year-old man with chronic myelomonocytic leukemia (CMML) that was complicated by fatal respiratory failure. Bilateral pulmonary infiltrates were demonstrated by chest roentgenograms and worsened with an increase in the leukocyte count. Postmortem examination confirmed the presence of leukemic monocyte infiltration of the pulmonary interstitial spaces. In CMML with marked monocytosis, respiratory failure may be one of the important causes of death in addition to infection and bleeding. PMID- 1620982 TI - A case of bronchiolitis obliterans organizing pneumonia associated with primary Sjogren's syndrome who died of superimposed diffuse alveolar damage. AB - Bronchiolitis obliterans organizing pneumonia (BOOP) developed in association with primary Sjogren's syndrome in a 69-year-old female. She died of diffuse alveolar damage superimposed on BOOP in spite of corticosteroid therapy. PMID- 1620983 TI - A case of cyclophosphamide-induced interstitial pneumonitis diagnosed by bronchoalveolar lavage. AB - A successfully treated case of cyclophosphamide pneumonitis, which developed during treatment for a leukemic phase of B-cell non-Hodgkin's lymphoma, is documented. Subtyping of lymphocytes in the peripheral blood and the bronchoalveolar lavage fluid easily excluded a possible diagnosis of pulmonary involvement of lymphoma. Bronchoalveolar lavage is a useful approach to determine the correct etiology of pneumonitis. PMID- 1620984 TI - Nonvagal modulation of hypoglossal neural activity. AB - Upper airway dilating muscle activity is characterized by an early-peaking pattern which serves to dilate or stiffen the upper airway at the time when the greatest negative intraluminal pressure is generated by contraction of chest wall muscles. This pattern has been attributed to phasic afferent inputs from pulmonary stretch receptors. The present study examines the hypothesis that nonvagal factors may also influence the discharge pattern and coordination of upper airway and chest wall muscle activities. Therefore, in anesthetized, paralyzed, vagotomized and artificially ventilated cats, we examined the effects of changes in respiratory drive produced by activation of cholinergic and GA BAergic (gamma-aminobutyric acid) receptors at the ventrolateral aspects of the medulla oblongata on phasic intrabreath discharge patterns of hypoglossal and phrenic nerves. Cholinergic agents (acetylcholine, carbachol, methacholine, physostigmine) applied directly to chemoreceptive areas on the ventral medullary surface increased hypoglossal activity, and in addition converted inspiratory discharge from an augmenting to a decrementing pattern of activity. The reverse effect on the discharge pattern of hypoglossal activity was observed with a decrease in respiratory drive. While the amplitude of the phrenic nerve discharge was also affected by these interventions, the augmenting discharge pattern of phrenic nerve activity did not change. These results suggest that the early peaking pattern of hypoglossal nerve discharge in vagotomized cats also depends on the level of respiratory drive, and is not solely dependent on vagal afferent inputs. In addition, the data suggest that structures near the ventral surface of the medulla are influential in shaping the pattern of hypoglossal nerve activity and maintaining balanced activity of upper airway and chest wall muscles. PMID- 1620985 TI - Inhibition of mouse alveolar macrophage production of tumor necrosis factor alpha by acute in vivo and in vitro exposure to tobacco smoke. AB - We investigated the effects of tobacco smoke exposure on the production of tumor necrosis factor alpha (TNF alpha) by alveolar macrophages (AM) in mice (C57BL/6). The results obtained are as follows: (1) In vivo tobacco smoke exposure caused a significant decrease in the production of TNF alpha by AM with the stimulation of lipopolysaccharide (LPS; control group: 19.32 +/- 5.52 U/ml, smoked group: 4.28 +/- 0.98 U/ml; p less than 0.05). (2) In vitro exposure of AM to tobacco smoke extracts (water-soluble extracts) also caused a decrease in the production of TNF alpha up to 93% of control with stimulation of LPS (p less than 0.05) without any decrease in cellular viability. We concluded that the production of TNF alpha by AM was impaired by smoking via direct action of the factors present in tobacco smoke. PMID- 1620986 TI - Analysis of respiratory impedance characteristics in chronic bronchitis. AB - Impedance measurements of the respiratory system were performed by means of the technique of forced oscillations to study the mechanical characteristics of the respiratory system in 33 patients with chronic bronchitis without spirometric evidence of airway obstruction (FEV1 greater than or equal to 70% predicted). In 23 patients (69.7%) impedance was found to be abnormal. Inhalation of a beta 2 adrenergic drug (terbutaline) resulted in acute reversibility of these findings. In the 10 patients (30.3%) with a normal baseline respiratory impedance, isocapnic hyperventilation with cold air resulted in impedance characteristics similar to the abnormalities spontaneously occurring in the other group. These changes were found to be completely reversible after the inhalation of terbutaline. On the basis of these findings we conclude that impedance measurements of the respiratory system by means of the technique of forced oscillations allow the determination of mechanical airway abnormalities in patients with chronic bronchitis. PMID- 1620987 TI - Influences of the cellular and humoral immune system in bronchoalveolar lavage on lung function in pulmonary sarcoidosis. AB - We investigated the changes in the cellular and humoral immune system in bronchoalveolar lavage (BAL) performed in 22 patients with pulmonary sarcoidosis and in 14 normal control subjects and their interactions with lung function parameters. Lymphocytosis, the increase in OKT4+ lymphocytes and OKT4+OKDR+ lymphocytes correlated with the increase in immunoglobulins, especially IgG, IgA and kappa chain assembled immunoglobulins. The transferrin levels obtained in BAL were found to be higher in patients with sarcoidosis, and they correlated with the cellular and, more closely, with other humoral findings. A negative correlation existed between the ventilatory parameters and the cell count and humoral findings. In addition, we found a negative correlation between the diffusing capacity for carbon monoxide and other cellular findings, which was most pronounced with reference to lymphocytes, OKT4+ lymphocytes and the OKT4+/OKT8+ ratio. These results underscore the role of OKT4+ lymphocytes, activated OKT4+OKDR+ lymphocytes and transferrin in the increase in immunoglobulins, mainly kappa chain isotypes. Because of the relationship between these changes and ventilatory parameters, and the diffusing capacity, the above results also reveal the clinical relevance of our findings. PMID- 1620988 TI - Herpes zoster in patients with sarcoidosis. AB - 108 patients with sarcoidosis were retrospectively studied for the development of herpes zoster. Five of these patients (4.6%), 2 of whom were in their twenties, developed herpes zoster. Only 1 patient had been treated with an oral steroid. All 5 had extrathoracic lesions. Zoster tended to occur during the inactive stage of sarcoidosis and did not exacerbate the activity of the sarcoidosis. The clinical course of their zoster infection was typically benign. There have been few reports of herpes zoster in patients with sarcoidosis. Further studies are required to determine whether sarcoidosis predisposes to herpes zoster infection. PMID- 1620989 TI - [Molecular and cellular biology in the bronchopulmonary development]. PMID- 1620990 TI - [Coronary thrombolysis in patients with acute myocardial infarction]. PMID- 1620991 TI - [Non-invasive pulmonary function tests]. PMID- 1620992 TI - [Epidemiology and biostatistics in medical research. 4. Validity, reliability, and multiple comparison]. PMID- 1620993 TI - [P0.1 as an indicator for weaning]. PMID- 1620994 TI - [Heart diseases in the elderly. (1) Treatment of cardiac arrhythmia in the elderly]. PMID- 1620995 TI - [Early diagnosis of the site of infarction and the infarct-related coronary artery in patients with acute inferior myocardial infarction]. AB - We evaluated the site and infarct-related arteries from electrocardiograms (ECGs) recorded early after the onset in cases of inferior infarction (IMI). The subjects were 80 patients with IMI admitted within 6 hours from the onset. We analyzed the ECGs on admission, at 24 hours, at 4 weeks. All patients underwent ventriculography and coronary angiography at 4-6 weeks from the onset. Regional wall motion and ejection fraction (FF) were measured. The infarct-related artery was decided on by the site of the asynergy. Patients were allocated into 2 groups according to the infarct-related artery; ie right (RCA, n = 52) and left circumflex (LCX, n = 52). Parameters measured were leads showing ST elevation (ST increases), width of R waves and R/S ratio in V1,2. Amplitude of U waves in V1-3. We defined U greater than or equal to 0.5mm as abnormal (GU). A significantly greater number of patients with GU showed asynergy in posterolateral and posterobasal segments compared to those without GU. The EF was significantly lower in patients with GU. As to the infarct-related arteries, a significantly greater number of patients with LCX disease showed concomitant posterior infarction (PMI) than those with RCA disease. Also a significantly greater number of those with LCX disease showed GU and ST increases in V5,6 than those with RCA disease. Therefore, we conclude that GU in V1-3 is a new marker suggesting posterolateral and posterobasal damage, and GU in V1-3, ST increases in V5,6 and electrocardiographic PMI are specific markers for the diagnosis of LCX related infarction. PMID- 1620997 TI - [Usefulness of magnetic resonance imaging (MRI) in evaluation of left ventricular apical aneurysm]. AB - Twenty three consecutive cases of left ventricular aneurysm due to antero-septal myocardial infarction in normal sinus rhythm were studied to decide whether or not magnetic resonance imaging (MRI) can evaluate aneurysm of the left ventricular apex. The apex, as well as the base, of the left ventricle was clearly imaged in 21 out of 23 cases. Poor images were obtained in two cases who showed frequent premature ventricular beats during this procedure. Two dimensional echocardiography has weak points when visualizing left ventricular apex because, for one thing, the sector angle is maximally 90 degrees, and for another, the cardiac apex is too near the probe for observation of the characteristic of the left ventricular apical wall. However, MRI can make up for the above weak points and can provide supportive information by visualizing the entire left ventricular apex. PMID- 1620996 TI - [Extravascular thermal volume in pulmonary emphysema]. AB - The extravascular thermal volume of the lung (ETVL) was measured by the heat sodium double indicator dilution technique in 10 patients with chronic pulmonary emphysema. ETVL was 4.99 +/- 1.23 ml/kg, and correlated significantly with TLC(r = 0.747), %VC(r = 0.664), PaO2(r = 0.779), AaDO2(r = -0.796), shunt ratio(r = 0.7), and total pulmonary vascular resistance(r = 0.698). ETVL tended to decrease with the progression of the severity of emphysema as assessed by computed tomography. These results suggest that 1) the extravascular thermal volume decreases in chronic pulmonary emphysema parallel with an increase in the severity of the complaint, and that 2) the decrease of extravascular thermal volume may reflect a decrease in the size of the pulmonary capillary bed. It is concluded that the measurement of extravascular thermal volume may be useful for the evaluation of the severity of pulmonary emphysema. PMID- 1620998 TI - [Hypertrophic cardiomyopathy with rapid development of giant negative T-wave within a year: a case report]. AB - A 61-year-old female was admitted to our hospital, presenting hypertension and giant negative T-wave (GNT) on an electrocardiogram (ECG). The ECG taken one year prior to the admission showed left ventricular hypertrophy (LVH) without GNT. Hypertension had been poorly treated during the year previous to her admission. These had been almost no administration of antihypertensive drugs. Echocardiograms, left ventriculograms and magnetic resonance imaging revealed concentric and diffuse LVH. Endomyocardial biopsy of bilateral ventricles disclosed a degeneration of myocytes and their bizarre hypertrophy with disorganization. This pathologic finding was compatible with that of hypertrophic cardiomyopathy (HCM). Although GNT has frequently been noted in apical type of HCM, the alteration from normal T-wave to GNT within a year has rarely been reported. The present case exhibited GNT on an ECG which showed no apical hypertrophy. Since GNT had developed within a year while hypertension was poorly treated, the rapid development of GNT might have been precipitated by hypertension, which possibly altered the hypertrophic pattern of the left ventricle. PMID- 1620999 TI - [A case of successful repair of aorto-pulmonary artery fistula secondary to aortic arch aneurysm]. AB - A report of a rare case of successful repair of rupture of an aortic aneurysm into the pulmonary artery. A 55-year-old male was transferred to our hospital because of dyspnea with sudden onset, hemoptysis and palpitation. A loud, continuous, "machine-like" murmur was heard on the anterior wall of the chest. Various examinations revealed an acquired shunt between the thoracic aortic aneurysm and the pulmonary artery and high-output heart failure. Aortic arch replacement was performed expeditiously and the patient recovered, and was able to return to work. 108 cases of rupture of a thoracic aortic aneurysm into the pulmonary artery have been reported in the literature. Operation for repair was performed in only thirteen of these. Only four cases have been reported in the literature in which the patients were successfully treated. PMID- 1621000 TI - [A case of atrial standstill associated with combined valvular disease]. AB - A 62-year-old man was admitted to our hospital because of general malaise. The chest X-ray film showed severe cardiomegaly (CTR = 81%). The electrocardiogram demonstrated absence of P wave in 12-leads and regular junctional rhythm with incomplete right bundle branch block. Echocardiogram and color Doppler led to the diagnosis of mitral stenosis and regurgitation, tricuspid regurgitation with enlarged left and right atrium. Cardiac catheterization study revealed elevation of the pulmonary artery wedge pressure and the right atrial pressure without A wave. In the electrophysiologic study, no atrial electrical activity was recorded in the right atrium and the coronary sinus. However, when atrial pacing was attempted at multiple sites with stimulum strength of 10 V, there was no atrial activity at various sites. We considered that the atrial overload due to combined valvular disease for seventeen years had resulted in total and persistent atrial standstill. In this report, we discussed atrial standstill in 67 cases recorded in the medical literatures in our country. PMID- 1621001 TI - Current research in side effects of high-dose chemotherapy. AB - The toxicities of chemotherapy continue to hamper dose escalation of specific chemotherapeutic agents. The impact of dose intensification upon survival will be assessed as clinical studies continue. Strategies to support chemotherapy dose intensification include BMT, use of CSFs and antiemetic drug combinations. Advances in symptom management will hopefully enhance quality of life for patients, whereas the development of chemoprotectant agents may allow specific organ toxicities to be avoided. PMID- 1621002 TI - Chemotherapy-induced myelosuppression. AB - Chemotherapy-induced myelosuppression is the most common dose-limiting and potentially fatal complication of cancer treatment. Prior attempts to lessen chemotherapy-induced myelosuppression have been minimally effective. The new hematopoietic growth factors show promise, especially for patients requiring intensely myelotoxic chemotherapy. However, a cautious approach should be used with growth factors because their clinical uses and how best to apply each use needs to be defined. PMID- 1621003 TI - Chemotherapy and pregnancy. AB - There are still unanswered questions concerning long-term effects of intrauterine exposure to antineoplastics. It is possible that a mechanism of follow-up such as a national registry could be formalized. Although pregnancy in the women with cancer is a rare event, it may occur more frequently in the future. The nurse must be knowledgeable concerning the issues in decision-making and confident in his or her ability to mobilize resources for the patient and family. Overall, the use of cytotoxic agents during the first trimester offers the greatest potential for spontaneous abortion and fetal malformations. In contrast, chemotherapy administered in the second and third trimesters appears to offer minimal risk. What effect this exposure will have on future generations is only speculative. It would be safer if fetal drug exposure could be avoided completely, but when this is not prudent and the mother's life is at stake, careful consideration and thoughtful guidance is appropriate for the pregnant patient with cancer. PMID- 1621004 TI - Long-term central venous catheters: issues for care. AB - Long-term central venous catheters allow the safe administration of chemotherapy, blood and blood products, total parenteral nutrition, fluids, and other medications. Despite their benefits, the risk of certain complications (e.g., fibrin sleeve and mural thrombus formation, infection, catheter occlusion, extravasation, and catheter malposition) exist for every person who has a catheter. Thus, preventative measures, recognition of early signs and symptoms of complications, and adequate care of utmost importance. PMID- 1621005 TI - Clinical trials: impact evaluation and implementation considerations. AB - It is commonplace for oncology nurses to care for patients entered on clinical trials. However, clinical research can impose a significant impact on the resources of sponsoring institutions or agencies, especially in today's environment of cost containment. Thus, institutions and nurses are increasingly involved in systematic resource impact evaluations to determine their commitment to cancer clinical trials. It is important for nursing to evaluate the impact of proposed clinical research and define the parameters for the participation of nursing service. PMID- 1621006 TI - Barriers and strategies for effective chemotherapy. AB - Chemotherapy offers the potential for cure or substantial palliation of numerous malignancies. However, its effective use requires a carefully developed strategy to overcome the barriers presented by a variety of neoplasms. Curative treatment for those human malignancies that show sensitivity to the available drugs requires combinations of drugs in "dose intense" regimens. Autologous bone marrow transplants and cytokines allow larger doses of drugs and possibly will improve the cure rates. Maximum compliance and prevention of drug toxicity are essential. PMID- 1621007 TI - The next generation: new chemotherapy agents for the 1990s. AB - The progress in cancer chemotherapy since the 1940s has been tremendous with over 40 cytotoxic agents, excluding hormones, that have undergone clinical trials and been approved by the Food and Drug Administration (FDA). Preclinical drug development and clinical trials have made this progress possible. Several new agents that are either undergoing clinical trials or have recently been approved by the FDA include idarubicin, ICRF-187, piroxantrone, all-trans-retinoic acid, fludarabine phosphate, taxol, and suramin. PMID- 1621008 TI - Drug interactions in the oncology patient. AB - Cancer patients receiving chemotherapy often require a wide range of drugs to manage symptoms of their cancer, the side effects of the chemotherapy or radiation therapy, and other concomitant illnesses. The greater number of drugs the patient receives the greater the chance of adverse reactions. Clinical drug interactions may be direct, indirect, and additive. Toxicity or an altered therapeutic response secondary to a drug interaction may affect the cancer patient's ability to tolerate and safely receive chemotherapy. PMID- 1621009 TI - [Characteristics of education of UOEH--towards further development in occupational health]. PMID- 1621010 TI - From research to practice. Role of a research institution in the development of the work environment. AB - To conclude, all the signals from the future working life and the society at large speak for the growing importance of research in the areas of environmental health and occupational health. This research, in order to have the best impact, should be guided by solid strategy based on the soundest health values presenting clear priorities, and directed to the preventive impact-oriented actions, and using the competence of highly motivated researchers. The researchers should be well supported by their research institutes with good operational capacity and facilities and be provided with close contacts with the consumers of the research. This would facilitate the application of research results in the practical work environment. If all these criteria are met we can also expect an impact. We are all called upon to take part in this exciting effort, and I am happy to state that the response of UOEH during its over 13 years of activity has been a most beautiful example for all of us. Let me transmit the warmest congratulations to UOEH for the past and wishes of success in the future. PMID- 1621011 TI - The mechanism of the action of IFN-gamma and TPA on the modulation of epidermal growth factor receptors of human amnion cells. AB - We have examined the mechanism of synergistic action occurring between interferon (IFN)-gamma and 12-0-tetradecanoylphorbol-13-acetate (TPA) with respect to the reduction of 125I-epidermal growth factor (125I-EGF) binding to human amnion (WISH) cells [Karasaki Y et al (1989) J Biol Chem 264: 6158-6163]. The cells were treated with protein kinase C (PKC) inhibitors (H7, staurosporine) to investigate the role of PKC in the synergism between IFN-gamma and TPA, since TPA is a strong activator of PKC. The combined effect of IFN-gamma and TPA was blocked by the PKC inhibitor, suggesting that PKC plays an important role in the synergistic action of TPA and IFN-gamma on the inhibition of EGF binding to the cells. The prolonged incubation (24 h) of the cells with TPA resulted in the restoration of EGF binding to the cells. A 24 h treatment of WISH cells with both IFN-gamma and TPA, however, still exhibited greater than 50% inhibition of EGF binding. No PKC activity, however, was observed in the WISH cells treated with both IFN-gamma and TPA for 24 h as well as with TPA alone for 24 h, indicating that IFN-gamma may synergize with the second mediator induced by PKC rather than PKC itself in the reduction of EGF binding to WISH cells. In addition, IFN-gamma showed the synergistic action with calcium ionophores on the reduction of EGF binding to the cells, suggesting that Ca2+ may be one of the second mediators which was induced by TPA and which cooperated with IFN-gamma. PMID- 1621012 TI - [The effect of the thyrotropin releasing hormone (TRH) on the motor speech disorder in spinocerebellar degeneration]. AB - A prospective study regarding the effect of TRH on the motor speech disorder of three patients with spinocerebellar degeneration (SCD), the first with hereditary cortical cerebellar atrophy, the second and third with sporadic olivo-ponto cerebellar atrophy, was performed. The effect was analyzed by using speech evaluation, such as the auditory impression, the questionnaire of the consciousness for verbal communication, the phonetic evaluation and the acoustic analysis. The results of the analysis and the mechanism of the improvement of the motor speech disorder are discussed. Only the first patient showed a remarkable improvement subjectively. In addition, the improvement of phonation and articulation was demonstrated quantitatively in the evaluation of the first patient. On the other hand, by phonation analysis using VISI-PITCH, it was seen that there were a decrease in the perturbation of the voice pitch and an increase in voice range in all three patients. Therefore, it was concluded that the improvement of phonation plays a major role in the improvement of the motor speech disorder. Such improvement of the phonation seems to have resulted from the improvement of coordination, mainly due to the normalization of the muscle tone of the larynx by TRH administration. Although a remarkable beneficial effect of TRH may be obtained in exceptional patients of SCD, the mechanism of such an effect of TRH should be more extensively studied using the quantitative clinical evaluation of phonation and articulation. PMID- 1621013 TI - ["Toxins" and nerve--a discussion on the pathogenesis of acrylamide intoxication, giant axonal neuropathy and Krabbe disease]. AB - A common mechanism appears to play a pathogenetic role in acrylamide intoxication, which is due to an exogenous cause, and in giant axonal neuropathy, an intrinsic disorder. In giant axonal neuropathy, a genetic defect in the processing of an intrinsic acrylamide or acrylamide-like substance may be postulated. On the other hand, the devastating pathology in Krabbe disease (a genetic disorder affecting almost exclusively the nervous system) appears to be due to the effects of psychosine, a toxic lipid produced in the nervous system. These suggest that the "toxicological approach" can be more diverse and of greater use than usually considered. PMID- 1621014 TI - [Quantitative study of the secretion, action and metabolism of insulin in man]. PMID- 1621015 TI - [Congenital arteriovenous malformations of the limbs: apropos of 4 cases]. PMID- 1621016 TI - [Ablation of accessory bundles using radiofrequency current]. PMID- 1621017 TI - [Tinea of the scalp in the region of the river Meuse: a current renaissance?]. PMID- 1621018 TI - [Infestational delirium: entomophobia, acarophobia, parasitic dermatophobia. Psychopathology and therapy]. PMID- 1621019 TI - Sleep architecture and continuity measures of neonates with chronic lung disease. AB - Electroencephalographic (EEG) sleep studies of 25 preterm neonates with chronic lung disease (CLD) corrected to a fullterm postconceptional age were compared with recordings from two groups of neonates without CLD: a fullterm appropriate for gestational age group (9 patients) and a preterm group studied at a corrected term postconceptional age (15 patients). Electrographic/polygraphic studies were obtained using 21-channel EEG recordings. Scores were tabulated based on minute by-minute visual analyses of sleep state, number and duration of arousals, body movements and rapid eye movements (REM). A significant reduction in the percentage of active sleep was noted in the CLD group compared to both control groups (31.15% vs. 47.01% and 52.9%, respectively). The mean percentage of indeterminate sleep was significantly increased in the study group as compared to both control groups (31.23% vs. 15.18% and 11.5%). In addition, significant differences were noted between the CLD group and the healthy preterm control group with respect to the number (0.29/minute vs. 0.13/minute) and duration (4.8 seconds vs. 2.94 seconds) of arousals as well as the total number of body movements (1.57/minute vs. 0.74/minute). These data suggest that neurophysiological organization of the immature brain, as reflected in neonatal sleep architecture and continuity measures, is adversely affected in neonates with CLD. EEG sleep architecture and continuity measures may be helpful in predicting the longitudinal outcome of infants with CLD as this group is at risk for adverse neurodevelopmental outcome. PMID- 1621020 TI - Cognitive and motor performance of narcoleptic and normal subjects living in temporal isolation. AB - Six unmedicated narcoleptic subjects and nine normal controls lived in a temporal isolation laboratory for 18-22 days. They were permitted to "free-run" for the last 9-13 days. Brief cognitive and motor performance tests were repeated on average six times per subjective day. They consisted of serial search, complex verbal reasoning tasks and manual dexterity of each hand. Only minor differences in performance were found between the narcoleptic subjects and controls. Narcoleptic subjects showed mild impairment of accuracy on the search task that could be explained by occasional lapses and an afternoon dip in performance. Narcoleptic subjects also tended to perform some tasks more slowly, but the group differences were not significant. Neither speed nor accuracy of performance of narcoleptic subjects decreased over the course of the experiment. By one standard of performance, therefore, all or nearly all of the sleep need of these subjects was met by the sleep they obtained in the laboratory. That amount, in turn, did not exceed the total sleep obtained by the normal controls. Significant time-of day effects were found in narcoleptic subjects for speed of verbal reasoning (progressive slowing over the course of the day), manual dexterity (fluctuations in speeds) and accuracy of serial search (afternoon dip). These variations in performance could not be attributed to changes in core body temperature or to occurrences of naps or meals. PMID- 1621021 TI - Short-term triazolam use improves nocturnal sleep of narcoleptics. AB - This study was undertaken to determine whether the use of triazolam by narcoleptic patients leads to improvement of nighttime sleep or excessive sleepiness. Ten narcoleptic patients, 5 males and 5 females, with complaints of sleep disturbance and aged between 18 and 60 years, were assigned to a single blind within-subject crossover-designed study comparing placebo with 0.25 mg triazolam. All subjects completed sleep questionnaires and underwent 6 nights of polysomnographic testing. Following an adaptation night, subjects received either triazolam or placebo for 2 nights. Objective tests of sleepiness (multiple sleep latency testing/maintenance of wakefulness test) were performed. Sleep efficiency and overall sleep quality were improved on all triazolam nights. Daytime excessive sleepiness was not reduced objectively after triazolam. This study demonstrates that the short-term use of triazolam improves nocturnal sleep quality in narcoleptics. Studies of long-term administration of triazolam are required to determine if the improvement of nocturnal sleep is maintained. PMID- 1621022 TI - Isolated sleep paralysis elicited by sleep interruption. AB - We elicited isolated sleep paralysis (ISP) from normal subjects by a nocturnal sleep interruption schedule. On four experimental nights, 16 subjects had their sleep interrupted for 60 minutes by forced awakening at the time when 40 minutes of nonrapid eye movement (NREM) sleep had elapsed from the termination of rapid eye movement (REM) sleep in the first or third sleep cycle. This schedule produced a sleep onset REM period (SOREMP) after the interruption at a high rate of 71.9%. We succeeded in eliciting six episodes of ISP in the sleep interruptions performed (9.4%). All episodes of ISP except one occurred from SOREMP, indicating a close correlation between ISP and SOREMP. We recorded verbal reports about ISP experiences and recorded the polysomnogram (PSG) during ISP. All of the subjects with ISP experienced inability to move and were simultaneously aware of lying in the laboratory. All but one reported auditory/visual hallucinations and unpleasant emotions. PSG recordings during ISP were characterized by a REM/W stage dissociated state, i.e. abundant alpha electroencephalographs and persistence of muscle atonia shown by the tonic electromyogram. Judging from the PSG recordings, ISP differs from other dissociated states such as lucid dreaming, nocturnal panic attacks and REM sleep behavior disorders. We compare some of the sleep variables between ISP and non ISP nights. We also discuss the similarities and differences between ISP and sleep paralysis in narcolepsy. PMID- 1621023 TI - Prominent eye movements during NREM sleep and REM sleep behavior disorder associated with fluoxetine treatment of depression and obsessive-compulsive disorder. AB - The clinical polysomnographic (PSG) reports of 2,650 consecutive adults studied during 41 months were reviewed retrospectively to identify all patients treated with fluoxetine or tricyclic antidepressants. The PSG reports of four other adult groups were also reviewed: periodic limb movement (PLM) disorder (n = 28); sleep terror/sleepwalking (ST/SW) (n = 54); rapid eye movement (REM) sleep behavior disorder (RBD) (n = 70); patients with clinically unremarkable sleep during two consecutive PSG studies (n = 30). Standard PSG recording and scoring methods were employed. A total of 1.5% (n = 41) and 2.0% (n = 52) of patients were receiving fluoxetine or tricyclics (amitriptyline or nortriptyline, n = 31; imipramine or desipramine, n = 16; protriptyline or trimipramine, n = 5). A selective association between fluoxetine and extensive, prominent eye movements in nonrapid eye movement (NREM) sleep was detected, utilizing Fisher's exact one-tailed statistic (p less than 0.00001 for each comparison). The detection rates were fluoxetine, 48.8% (20/41); tricyclics, 5.8% (3/52); RBD, 4.3% (3/70); objectively normal sleepers, 3.3% (1/30); PLM, ST/SW, 0% (0/82). These groups had similar mean ages (31.5-45.4 years) and gender distributions (50.0-60.7% male), apart from RBD. The effect of fluoxetine, a potent and specific serotonin reuptake inhibitor, on NREM eye movements is postulated to derive from potentiation of serotonergic neurons that inhibit brainstem "omnipause neurons", which, in turn, inhibit saccadic eye movements, thus resulting in disinhibited release of saccades. In addition, a 31-year-old man with obsessive-compulsive disorder developed RBD soon after starting fluoxetine therapy, which persisted at PSG study 19 months after fluoxetine discontinuation. PMID- 1621024 TI - The evoked K-complex: all-or-none phenomenon? AB - The functional significance and topographical variation of the different components of the evoked K-complex were examined. In the first experiment, the intensity of the stimulus (80 and 60 dB SPL) and its rise-and-fall time (2 and 20 milliseconds) were manipulated during nonrapid eye movement sleep. In the second experiment the tonal frequency (500, 1,000 and 2,000 Hz) of the stimulus was manipulated. In the first experiment, nine stimuli were presented every 10 seconds, whereas in the second, 20 consecutive stimuli were presented. The evoked K-complex consisted of two different negative components peaking at approximately 350 and 550 milliseconds, respectively, and followed by a positive component peaking at approximately 900 milliseconds. K-complexes were easier to elicit for high-intensity fast rise-and-fall time stimuli than for low-intensity slow rise and-fall time stimuli. The probability of occurrence was not affected by the tonal frequency of the stimulus. When a K-complex was evoked, the amplitude and latency of N350, N550 and P900 remained invariant regardless of its intensity, rise-and-fall or its tonal frequency. The N550-P900 portion of the K-complex therefore appears to be an all-or-none phenomenon. On trials in which a K-complex could not be elicited, N350 was still visible although much attenuated. In these trials, its amplitude was further reduced when stimulus intensity was lowered. N350 might need to reach a certain critical threshold before the much larger N550 P900 complex is elicited. PMID- 1621025 TI - Sleep in normal late pregnancy. AB - Twelve women in their third trimester of pregnancy and 10 age-matched nonpregnant controls underwent complete polysomnography for one night in the laboratory. Seven of the original women returned for a second study 3-5 months postpartum. During late pregnancy, women showed increased wake after sleep onset (WASO) and a lower sleep efficiency in comparison with the control group. The percentage of rapid eye movement (REM) sleep was significantly decreased and the percentage of stage 1 significantly increased compared to the nonpregnant group. At 3-5 months postpartum, a significant reduction in WASO and increased sleep efficiency were noted. However, only a slight increase was noted in REM sleep during the postpartum period compared to the prepartum period. The most frequent sleep complaints in the pregnant group were restless sleep, low back pain, leg cramps and frightening dreams. In summary, in accordance with their complaints, women in their third trimester demonstrated polysomnographic patterns of sleep maintenance insomnia. PMID- 1621026 TI - Biperiden administration during REM sleep deprivation diminished the frequency of REM sleep attempts. AB - Sixteen subjects were assigned to a group using either placebo or biperiden, with eight subjects in each group. Both groups were studied for one acclimatization night, one baseline night, four nights of rapid eye movement (REM) sleep deprivation and two recovery nights. All the subjects received either placebo or 4 mg biperiden 1 hour before sleep during the four nights of REM sleep deprivation. During the baseline and the recovery nights both groups received placebo capsules. The results showed that REM sleep time during the REM sleep deprivation was reduced by 70-75% below the baseline night in both groups. The number of attempts to enter REM sleep was significantly reduced by biperiden as compared to placebo for each of the four REM sleep deprivation nights. Because the total sleep time in the biperiden group was reduced, the number of REM sleep attempts was corrected by the total sleep time. The adjusted number of REM sleep attempts was also significantly reduced in the biperiden group. REM sleep latency showed a reduction in the placebo group, whereas in the biperiden group REM sleep latency was unchanged throughout the deprivation nights. In the recovery night REM sleep time was increased in both groups, with no differences between the groups. The REM sleep latency showed a reduction in the first recovery night in both groups that persisted through the second recovery night. The above findings support the role of biperiden as a REM sleep suppressive drug. PMID- 1621028 TI - Preliminary report: validity of symptom analysis and daytime polysomnography in diagnosis of sleep apnea. AB - The aim of this study was twofold: first, to see if the prevalence of the sleep apnea syndrome (SAS) in a given population could be fairly estimated by our patient questionnaire, mainly based upon the 1979 American Sleep Association definition of SAS; and second, to investigate whether the severity of SAS could be similarly accurately measured by daytime polysomnography (DPSG), as an alternative to the more demanding all-night polysomnography (NPSG). Of 42 patients consecutively examined due to rhonchopathy, 18 had the clinical diagnosis of SAS, which was based on the three symptoms--snoring, sleep disturbances and diurnal hypersomnia--if reported to occur habitually. In 11 patients the diagnosis was established by NPSG [apnea index (AI) greater than 10]. However, in only 10 of the 18 cases NPSG indicated the diagnosis giving a positive predictive value of 56%. When comparing DPSG versus NPSG in 36 patients, the AI ranged from -23 to +65, and the mean AI value was found to be twice as high in the former (mean difference 9.0 +/- 18.4; p less than 0.01). The positive predictive value of DPSG was 63% (10/16). Both the self-report and DPSG were burdened with some 25% false-positive results, and DPSG gave far too variable AI values to be reliable in staging the disease. On the other hand, the negative predictive values were high, 96% (23/24) and 100% (20/20), respectively, indicating their usefulness for screening purposes. PMID- 1621027 TI - Accuracy and significance of scoring hypopneas. AB - We previously reported that the best definition of hypopneas in the sleep apnea/hypopnea syndrome (SAHS) is based on reduction in thoracoabdominal movement. However, the repeatability of scoring hypopneas from thoracoabdominal movement has not been assessed, nor has the need to record flow as well as thoracoabdominal movement. Thus, two polysomnographers independently scored both apneas and hypopneas on all-night polysomnograms of patients with SAHS. There was close agreement between the polysomnographers for the number of hypopneas (r = 0.98; mean difference 11%) and for the number of apneas (r = 0.99; mean difference 8%). The agreement was similar for the durations of both hypopneas (r = 0.99; mean difference 13%) and apneas (r = 0.99; mean difference 11%). There was also close agreement between the total number of respiratory events scored with and without reference to the flow signal (r = 0.99; mean difference 1.4%) with a maximum under-recognition of 18 events per night in a subject with 237 apneas per night. Thus, hypopneas can be scored reproducibly. In addition, the value of always recording and scoring flow as well as thoracoabdominal signals is questioned. PMID- 1621029 TI - Charles Dickens: observer of sleep and its disorders. AB - Using the characters of his novels as the canvas, Charles Dickens painted vivid word pictures of a variety of manifestations of sleep and its disorders. These were presumably based on the author's own experiences and those of family and friends. Dickens was, himself, a self-confessed episodic insomniac. For this he devised the unique therapy of long night walks. This article illustrates, by a few selected quotations, this hitherto unpublicized aspect of the author's life and works. PMID- 1621030 TI - The clinical use of the Multiple Sleep Latency Test. The Standards of Practice Committee of the American Sleep Disorders Association. PMID- 1621031 TI - Bibliography of recent literature in sleep research. PMID- 1621032 TI - [Duodenal peptic ulcer]. PMID- 1621033 TI - [Late complication of diabetes mellitus of pancreatic origin]. AB - At Instituto Nacional de la Nutricion SZ in Mexico City, we reviewed 30 years of experience and selected 46 patients with Pancreatic Diabetes (PD), without family history of Diabetes Mellitus (DM) with at less two years of follow-up. Alcoholic chronic pancreatitis (CP) was found in 36 patients, in seven it was idiophatic and in three was secondary to pancreatectomy. We compared the evolution of this patients with a group of (DM) patients similar in age, sex, glucemic control and time of onset. There were no statistical differences between groups in the follow up of diabetic complications, only it was found a tendency to have higher lipid levels, macroangiopathy and retinopathy in those with DM. We concluded that CP have similar evolution as DM and could have deleterous complications in the large follow up. PMID- 1621034 TI - [Crohn disease. Medico-surgical experience. A 10-year retrospective study]. AB - Crohn's disease is rare in Mexico. The regarding of this pathology at Gastrointestinal Unit of the General Hospital of Mexico city, between january 1980 and december 1989, is presented. There were six cases of Crohn's disease, two women (33%) and four men (66%). The definitive diagnosis was done preoperatively only in one case, the other were diagnosed postoperatively. In all, intestinal obstruction was the surgical indication. A patient died (16.6%), three cases were followed for 12 months, only two patients are still under surveillance after 15 months. PMID- 1621035 TI - [Neoplastic polyps of the colon]. AB - We report all patients with neoplastic polyps endoscopically excised during 10 years, performed in different hospitals in Mexico City. All ages, both sexes and socio-economic levels were seen in several endoscopy services both, public and private. We find 190 patients (100 females) with 268 polyps and a mean age of 54.5 (range 18-86). Tubulo-villous adenomas have the less frequency (8%). Villous adenomas were the largest and had a 11% frequency, almost all were confined to recto-sigmoid region its mean age was 6 years. Villous adenomas were the most frequent (69%) distributed in all colonic segments, its mean age was 54.5 years with the widest range (18-80 years); they have highest dysplasia rate (8.1%). Carcinomas arising in polyps were all located in recto-sigmoid region, with female predominance (2.3:1) and oldest mean age of presentation (66.3 years). Neoplastic polyps in Mexico City general population has a low frequency; endoscopic polypectomy is safe and had a low morbi-mortality rate. PMID- 1621036 TI - [Surgical treatment of achalasia]. AB - Primary achalasia is a motor dysfunction of the esophagus with unknown aetiology. We present our results obtained in 39 patients treated by Heller's Cardiomyotomy. The procedure was successful in 92.3% of the cases and when it is performed in conjunction with an antirreflux technique, it offers excellent results with a very low frequency of gastroesophageal reflux symptoms and complications. PMID- 1621037 TI - [Peptic acid disease associated with Helicobacter pylori in children. Report of a case]. AB - We studied a child with peptic acid disease which was associated with H. pylori. The identification of H. pylori was done by biopsy and for antibody test. Clinical improvement was observed only with the use of amoxocilin and Bismuth subsalycilate. PMID- 1621038 TI - [Cholera: history, diagnosis and clinical management]. PMID- 1621039 TI - [Once an ulcer, always an ulcer? Therapy and management of duodenal ulcer]. PMID- 1621040 TI - The changing face of orthodontics. PMID- 1621041 TI - [Drug addiction and pregnancy]. AB - In drug-addicted women pregnancy is always at risk and difficult to supervise owing to the social and psycological profiles of these women. At the moment, we are dealing in France mainly with pregnancies that occur in heroin addicts and frequently have the following complications: lack of follow-up, prematurity, short child stature, infections (notably HIV infection) and weaning syndrome in the newborn. Due to improvements in the management of these patients, the neonatal mortality has been considerably reduced and has become exceptional. In the USA the number of pregnancies occurring in cocaine addicts has increased, and complications similar to those of heroin addicts have been observed, particularly with crack. It is not impossible that we might soon be confronted with this type of drug addiction. PMID- 1621042 TI - [Consensus conference on the screening of congenital hip dislocation. Paris 4 November 1991]. PMID- 1621043 TI - [What "clandestin" abortion was. Medical aspects]. PMID- 1621044 TI - [Retinal detachment. Etiology, diagnosis, principles of preventive and therapeutic measures]. PMID- 1621045 TI - [Trigeminal neuralgia. Diagnosis]. PMID- 1621046 TI - [Bacterial endocarditis. Etiology, physiopathology, diagnosis, development, prognosis, principles of the treatment]. PMID- 1621047 TI - [Nasal obstruction. Diagnostic orientation]. PMID- 1621048 TI - [Multiple trauma. Management ot the site of the accident]. PMID- 1621049 TI - [Agitation state. Diagnostic orientation and principles of emergency treatment]. PMID- 1621050 TI - [Asthma. Physiopathology, diagnosis, development, prognosis, principles of the treatment]. PMID- 1621051 TI - [When should eye infection be suspected?]. AB - During simple inspection of an inflamed eye it is often difficult to diagnose an infection. However, infection must be suspected, notably in cases with facilitating factors. Eye infection requires management by specialists to prevent complications which might endanger vision. PMID- 1621052 TI - [Principles of the treatment of ocular infections]. AB - Ocular infections are still quite common and their clinical presentation is variable; some of them may lead to blindness. In this paper only severe infections like keratitis and endophthalmitis are considered. The rationale for treatment and prophylaxis is based upon bacteriological findings, understanding of ocular barriers and pharmacokinetics of antibacterial agents. PMID- 1621053 TI - [Conjunctivitis and lacrimal apparatus infections]. AB - The term conjunctivitis covers all inflammatory processes affecting the conjunctiva. Bacterial and viral infections are the most frequent causes. Infectious conjunctivitis is rarely severe in industrialized countries, but trachomatous kerato-conjunctivitis is still the main cause of blindness all over the world. Most cases of bacterial conjunctivitis are treated with topical antibiotics. Viral conjunctivitis is frequent and, with the exception of herpetic conjunctivitis, has no specific treatment. Canaliculitis and dacryocystitis are rare but require specialized examination, treatment and follow-up. PMID- 1621054 TI - [Ocular herpes simplex]. PMID- 1621055 TI - [Non herpetic keratitis]. AB - Nonherpetic keratitis includes keratitis caused by other viruses, and bacterial, fungal, and acanthamoebic keratitis. Epidemic keratoconjunctivitis, one of the most common corneal manifestations induced by nonherpetic viruses, has usually a good outcome. Conversely, non viral keratitis has more severe complications. Early clinical and microbial diagnosis are the keystones to treat successfully these keratitis. Diagnostic and therapeutic principles are detailed in this review. PMID- 1621056 TI - [Infectious endophthalmitis]. AB - Bacterial endophtalmitis is a disastrous postoperative complication of any intraocular surgery which can lead to blindness. With prompt endocular taps for appropiate laboratory investigations, the use of large spectrum antibiotics with good intraocular penetration, the intraocular injections of antibiotics, most of the eyes can be salvaged. Although it is unlikely that postoperative microbial endophthalmitis can be avoided entirely, all efforts should be made to reduce the incidence of this complication. Under this point of view, in addition to the available sterile techniques during the surgery, the topical and systemic antibiotic prophylaxis requires that carefully controlled studies be performed on very large numbers of patients to attain statistical validity. PMID- 1621057 TI - [Ocular infections in immunodepressed patients]. AB - Two kinds of immunosuppression must be distinguished: malignant diseases on one hand, and acquired immunodeficiency syndrome on the other hand. Ocular infections can involve any part of the eye and they can lead to blindness. They usually attest of a systemic infection. Their treatment consist of an induction course to provide complete healing of the lesions, immediately followed by a maintenance course to prevent relapses. Retinitis are the most common posterior involvement, especially the retinitis due to cytomegalovirus and Toxoplasma gondii. Zoster ophtalmicus is the most common anterior involvement. Mucormycosis is rare but very severe. A closed collaboration between ophtalmologists and internists is mandatory to provide the most appropriate management of these infections. PMID- 1621058 TI - [Hematopoietic cell growth factors. What are the expectations today?]. PMID- 1621059 TI - [Epidemiology of type 2 diabetes. Elements of prevention]. PMID- 1621060 TI - [Nasopharyngeal fibroma. A mysterious tumor with unusual treatment]. PMID- 1621061 TI - [Salivary calculi]. AB - Salivary calculi are frequent and revealed by very painful signs, which need an urgent therapy. These calculi are more often localized in the submaxillary gland, sometimes in the parotid gland, and unfrequently in the sublingual glands. Their clinical signs include an increased volume of the gland (salivary hernia), pain of infectious complication. Diagnosis is confirmed by standard x-ray and sialography, which also predicate the localization of the calculi. The treatment is symptomatic including antispasmodic, sympatholytic and parasympathomimetic drugs and washings of the canal with antibiotic solutions. After few months of this treatment, the surgical treatment is indicated if the calculi stays in the canal. Depending on the localization of the calculi, the access way will be either endobuccal or external. PMID- 1621063 TI - Abstracts of papers presented at the 25th Scandinavian Conference on Gastroenterology and the 16th Scandinavian Meeting on Gastrointestinal Endoscopy. Bergen, Norway, 4-6 June 1992. Abstracts. PMID- 1621062 TI - [Immunology and psychiatry]. AB - This review of scientific literature comes within the interest arisen from ten years by psychoneuroimmunology, a field connecting several disciplines and illustrating in a new way the psychosomatic relationships. A first category of works has been dedicated to the study of psychiatric disorders associated with various diseases concerning immunity (systemic diseases, endocrine diseases, cancers, infectious diseases), but also to the possible effect of distressing life events on the upset activation of immune functions, or even to the discovery of predisposing personality profiles (type C profile, depressive vulnerability). A second category of works concerns the analysis of the immune disturbances associated with certain psychiatric diseases, such as depression or schizophrenia, but also with some distressing life conditions, like bereavement. Animal experimentation and human experimentation provide various informations on the factors conditioning the immunomodulating effects of stress, sometimes in the direction of an inhibition, sometimes in the direction of an activation of immune functions. Finally, several papers shed light on the immunomodulating effects of psychotropic drugs. All these works open new horizons to the scientific knowledge and let us glimpse an extension to the use of psychologic therapeutics, as well of pharmacological ones as of non pharmacological. PMID- 1621064 TI - Are we overestimating the genetic contribution to schizophrenia? AB - That genetic factors contribute to the etiology of schizophrenia is no longer debated; the nature and magnitude of that contribution, however, are still open for discussion. In this article, concordance rates for twin studies of schizophrenia are reviewed as one means of assessing the magnitude of the genetic contribution. Using only those studies in which representative samples were used and zygosity was determined with reasonable certainty, the pairwise concordance rate for schizophrenia was found to be 28 percent for monozygotic (MZ) and 6 percent for dizygotic (DZ) twins. Review of twin studies of other central nervous system diseases reveals that schizophrenia is most similar to multiple sclerosis (MZ concordance rate 27%). Although genetics remains as the single most clearly defined etiological factor in schizophrenia, the question remains whether we are overestimating the magnitude of the genetic contribution. PMID- 1621065 TI - When assessing twin concordance, use the probandwise not the pairwise rate. AB - Geneticists and twin researchers have long debated the relative merits of two alternative measures of twin concordance: the pairwise and probandwise concordance rates. The results of this debate are now quite clear, for almost every application the probandwise rate is preferred over the pairwise rate. In a recent review of schizophrenia twin studies, however, Torrey (1992) chose to analyze pairwise rather than probandwise rates. Torrey's use of pairwise rates led him to conclude that the monozygotic twin concordance for schizophrenia is weaker than what is widely accepted, and that, by implication, the magnitude of the genetic contribution to schizophrenia has been overestimated. In this brief commentary, we review the relative strengths and weaknesses of the pairwise and probandwise rates and show that Torrey's conclusion is based upon his incorrect use of pairwise rates. Twin studies of schizophrenia continue to support the existence of a strong genetic influence on the development of schizophrenia. PMID- 1621066 TI - First-episode psychosis: Part I. Editors' introduction. AB - Until recently, there has been a conspicuous lack of studies regarding the earliest phases of psychotic illness, with most research on schizophrenia and related disorders focusing on chronically ill patients. Currently, however, a number of investigators have turned their attention toward this topic, exploring the conceptual issues involved in defining the onset of psychosis, using case registers and population-based samples to do crucial epidemiologic studies on the course of schizophrenia, and developing mechanisms for identifying patients with first-episode psychosis and entering them into active research protocols. The issue of the Schizophrenia Bulletin is devoted to articles representing this full range of conceptual and empirical work on first-episode psychosis. The ultimate goal is for researchers working in this area to develop a network to enhance the sharing of concepts and data, with the eventual possibility of developing combined data bases and collaborative studies. PMID- 1621067 TI - Research on first-episode psychosis: report on a National Institute of Mental Health Workshop. AB - The need to focus increased research on patients experiencing their first episode of psychosis was emphasized in A National Plan for Schizophrenia Research. To develop strategies for enhancing research in this area, a National Institute of Mental Health Workshop on First-Episode Psychosis was held in 1991. The topics discussed at that workshop are summarized, with key issues including the following: (1) the need for better operational definitions of onset, end of an episode, and relapse of psychosis; (2) careful consideration of inclusion and exclusion criteria related to age, gender, prior treatment, comorbid substance abuse, and similar issues; (3) the challenge of finding patients never exposed to neuroleptics and the value of entering first-episode patients into standardized treatment protocols; (4) the design of followup studies; (5) strategies to increase the pool of applicants; and (6) approaches for increasing power through data sharing and collaboration between groups. PMID- 1621068 TI - The natural course of schizophrenia: a review of first-admission studies. AB - In this article, research on the natural course of illness among first-admission schizophrenic patients is reviewed from an epidemiological perspective. Three types of studies are considered: statistical reports dating primarily from the preneuroleptic era; long-term followback studies; and more recent prospectively designed cohort studies. Although relatively more first-admission patients have a positive course than do multiple admissions patients, the findings confirm the substantial heterogeneity in course and outcome. Methodological improvements in first-admission research are suggested, including separating the analyses of first-episode patients from those with past psychotic experiences; employing longitudinal methods for deriving diagnosis; including patients with drug and alcohol problems where appropriate; enlarging the samples either by multisite or multicenter collaborations or by pooling data across studies; and obtaining better data on treatment experiences in naturalistic research. PMID- 1621069 TI - Long-term course of hospitalization for schizophrenia: Part I. Risk for rehospitalization. AB - The probability of rehospitalization following the initial discharge on which a diagnosis of schizophrenia was made is described using data from psychiatric case registers in Victoria, Australia; Maryland, U.S.A.; Denmark; and Salford, England. The percentage eventually rehospitalized, after followup intervals as long as two decades, varies from about 50 to 80 percent in the four service systems. Survival curves for duration in the community without rehospitalization bend sharply in the period between 2 and 3 years following discharge in all four cohorts and are almost flat after 20 years. Early age of onset predicts higher risk for rehospitalization in multivariate proportional hazards models in each cohort. When age of onset is included as a covariate, neither gender nor marital status has consistent or statistically significant effects on risk for rehospitalization. PMID- 1621070 TI - Long-term course of hospitalization for schizophrenia: Part II. Change with passage of time. AB - This analysis examines the notion of progressive deterioration in schizophrenia, using long-term followup data on hospital episodes in defined cohorts from psychiatric case registers in Victoria, Australia; Denmark; and Salford, England. The analyses differentiate heterogeneity existing at the first hospitalization for schizophrenia, which produces a widely varying natural course, from heterogeneity that develops over time, as episodes of hospitalization occur. Episodes of hospitalization for schizophrenia tend to cluster earlier rather than later in the treatment career, suggesting a progressive amelioration rather than deterioration. When overall chronicity is adjusted, each additional episode of hospitalization lowers the risk for a further hospitalization by about 10 percent. PMID- 1621071 TI - The epidemiology of psychosis: the Suffolk County Mental Health Project. AB - This article describes the rationale, aims, and methodology of an epidemiological study of psychosis being conducted in Suffolk County, New York. A sample of first admission patients is drawn from 10 inpatient and 25 outpatient facilities. Diagnostic psychosocial interviews are conducted shortly after admission to treatment, and at 6- and 24-month followup. Consensus diagnoses are made after each interview. Demographic and clinical background characteristics of the first 250 subjects enrolled over a 2-year period are presented here. The response rate was 76 percent. Based on the initial interview, 75 percent of subjects received a diagnosis involving psychosis. The three most common diagnoses were schizophrenia, bipolar disorder with psychotic features, and major depression with psychotic features. Among subjects with psychosis, 58 percent of males and 29 percent of females had a history of substance abuse/dependence. Gender differences were found on several background and clinical characteristics. Males were somewhat younger, less likely to have ever married, and had less education. Although the median length of hospitalization was the same for females and males (27 days), females were more likely to be hospitalized within 1 month of the occurrence of their first psychotic symptom (60% of females compared to 37% of males). Subjects with schizophrenia-related disorders were significantly more impaired on an assessment of negative symptoms than were affectively ill subjects, but clinical ratings of depression were not significantly different across diagnostic groups. PMID- 1621072 TI - Anomalous lateral sulcus asymmetry and cognitive function in first-episode schizophrenia. AB - This study examines the cognitive functioning of first-episode schizophreniform patients within several weeks of hospitalization and at 2 years into the illness. Differences between patients and controls are also reported for measurements of the length of the lateral sulcus, which borders the planum temporal, an area of the brain integral to language function. Neuropsychological test results are also correlated to magnetic resonance imaging structural variables at the time of first hospitalization. Findings on neuropsychological summary scales reveal a diffuse pattern of cognitive impairment in schizophreniform patients compared to controls, which appears to improve over time. An atypical pattern of anatomic lateral symmetry is found in female schizophreniform patients, with female appearing to have a reduction in the normally occurring left greater than right length of the lateral sulcus. Such atypical asymmetry of the lateral sulcus is also associated with better cognitive function, particularly in schizophreniform patients. These findings suggest that atypical lateralization in an area critical to language function may be related to cognitive function in schizophreniform illness. PMID- 1621073 TI - The McLean First-Episode Psychosis Project: six-month recovery and recurrence outcome. AB - The McLean First-Episode Psychosis project began in 1989. The authors describe the study design, diagnostic distribution, and recovery and relapse data on the first 102 recruited subjects. Fifty-nine percent of the subjects had a diagnosis of bipolar disorder, 15 percent psychotic depression, 10 percent schizophrenic spectrum, 9 percent delusional disorder, and 8 percent other psychotic disorders. By 6 months, 80 percent recovered syndromically but only 55 percent recovered functionally, and only 50 percent recovered both functionally and syndromically. Non-white and male patients were more likely to have a recurrence. Men were less likely and bipolar patients were more likely to recover functionally. Patients with nonaffective psychosis had longer hospitalizations and lower rates of functional recovery 6 months after discharge. PMID- 1621074 TI - Neuropsychological and eye movement abnormalities in first-episode and chronic schizophrenia. AB - It is well known that neurobehavioral deficits are associated with schizophrenia. Little is known, however, about whether these disturbances becomes more severe over the course of the illness. In the present study, 101 patients with schizophrenia, of whom 45 were first-episode cases, performed pursuit eye tracking tasks. A subset of 60 of these patients, including 27 first-episode cases, were administered a battery of neuropsychological tests. Patients with a history of prior psychotic episodes demonstrated more severe pursuit eye movement dysfunction than first-episode patients and more severe disturbances on neuropsychological tests sensitive to prefrontal and left temporal cortical dysfunction. Longitudinal studies of patients ascertained close to the point of illness onset are needed to determine whether these findings reflect a progressive deterioration in neurobehavioral functioning over the course of schizophrenia. PMID- 1621075 TI - Electrodermal anomalies in recent-onset schizophrenia: relationships to symptoms and prognosis. AB - Electrodermal activity was measured in recent-onset schizophrenic patients (n = 98) and matched normal control subjects (n = 40) as part of an ongoing longitudinal study. Results at the initial inpatient test were generally consistent with the current consensus in the literature. A large subgroup of the patients was found to be nonresponsive with the phasic skin conductance orienting response measure, whereas the remaining subgroup of patients was found to be electrodermally tonically hyperaroused. Heightened electrodermal activity at the inpatient test was associated with a number of symptoms in male patients and with poor recovery from the acute schizophrenic episode. Followup tests conducted when the patients were in states of remission and psychotic relapse revealed that tonic electrodermal arousal measures qualify as state-sensitive episode indicators, whereas phasic nonresponding may qualify as an atypical vulnerability indicator. Moreover, preliminary data from three patients suggest that increases in tonic electrodermal arousal may temporally precede psychotic relapses. The principal findings are consistent with a vulnerability/stress model that posits that electrodermal hyperarousal is part of a transient intermediate state that may lead to a psychotic episode in a vulnerable individual. PMID- 1621076 TI - Are gender effects being neglected in schizophrenia research? AB - Research on schizophrenia published in four professional journals--Journal of Abnormal Psychology, Archives of General Psychiatry, Journal of Nervous and Mental Disease, and American Journal of Psychiatry--over a 5-year period from January 1985 through December 1989 was examined for gender composition of subject samples and gender analyses of findings. Results indicate a continued predominance of male subjects in schizophrenia research, with males outnumbering females two to one, and frequent neglect of possible gender differences within mixed-sex samples. Possible explanations for the male bias are considered and greater research and editorial attention to possible gender effects are urged. PMID- 1621077 TI - First person account: portrait of a schizophrenic. PMID- 1621078 TI - [Somatostatin analog (octreotide) in clinical use: current and potential indications]. AB - The long-acting somatostatin analogue octreotide is a synthetic cyclic peptide consisting of 8 amino acids. Depending on the organ, it acts either as a hormone or as a neurotransmitter. The effect on various physiological functions in the brain and the gastrointestinal tract is mainly inhibitory. Due to its inhibitory actions, the possibility of intravenous and subcutaneous administration and the lack of serious side-effects, octreotide offers a broad spectrum of possible indications. Today octreotide is recommended in acromegaly patients and for the treatment of hormone dependent symptoms in patients with gastroenteropancreatic tumours. New indications are enterocutaneous and pancreatic fistulas and the prevention of complications in major pancreatic surgery. In patients with dumping and short-bowel syndrome, octreotide may be helpful until dietary regimens are established. In Aids patients with severe diarrhea, octreotide can be used to stabilize patients with severe dehydration and malnutrition. The clinical effectiveness on upper GI-bleeding due to gastric ulcer and oesophageal varices is still controversial. Future studies must prove whether octreotide may be helpful in treating diabetic retino- and nephropathy because of the possibility of suppressing growth hormone and IGF-I. The antiproliferative effect of octreotide also allows its use in patients with somatostatin-receptor-positive, non-endocrine solid tumors (e.g. brain, breast and small-cell lung cancer). A promising area is the scintigraphic visualization of somatostatin-receptor positive tumors with a radio-labelled octreotide analogue and the possible target irradiation of these tumors by beta-particle emitting isotopes attached to such analogues. PMID- 1621079 TI - [Identification of crystals in synovial fluid: joint-specific identification rate and correlation with clinical preliminary diagnosis]. AB - The diagnostic clarification of joint effusions of unknown origin is a challenge to every primary-care physician. Important diagnostic procedures are arthrocentesis and analysis of the aspirated synovial fluid. Synovial fluid analysis frequently allows differentiation between harmless effusions due to osteoarthritis and crystal induced inflammation, or the more devastating septic arthritis. 4475 synovial fluids were evaluated retrospectively to calculate the identification rate of crystals compatible with calcium pyrophosphate dihydrate (CPPD) and monosodium urate monohydrate (MSUM). 40.8% (1827) of synovial fluids were taken from females and 59.2% (2648) from males. The frequency of crystal identification varied considerably: 13.2% CPPD crystal identification in females, 10.9% in males; MSUM was identified in 1.5% of females, and in 10.9% of males. The spectrum of joint involvement was nearly identical in CPPD and MSUM positive synovial fluids. Exceptions were the higher frequency of CPPD identification in shoulder joints (CCPD:MSUM = 15.6:1), the higher frequency of MSUM identification in the ankle (MSUM:CPPD = 15.6:1) and the first metatarsophalangeal joints (MSUM:CPPD = 8:1). Clinical suspicion correlated well with crystal identification in MSUM positive samples (60%), but was poor in CPPD positive samples (36%). The poor correlation between clinical suspicion and crystal identification in CPPD positive synovial fluids is explicable by the less characteristic clinical presentation of pyrophosphate arthropathy in contrast to classical gout. A high percentage of crystal identification was found in joints or periarticular swellings in which aspiration is difficult and therefore rare (e.g. tendon sheaths, first metatarsophalangeal and first metacarpophalangeal joints), underlining the importance of synovial fluid aspiration despite the difficulty of arthrocentesis. PMID- 1621080 TI - [Single cusp homograft implantation in the reconstruction of right ventricular outflow tract in the correction of tetralogy of Fallot]. AB - From 1987 to 1990, 37 children underwent surgical correction for tetralogy of Fallot. The mean age was 38.2 months (2-156 months). The indication for right ventricular outflow tract (RVOT) obstruction in 19/37 (51%) children was: hypoplastic pulmonary valve (n = 10), annular hypoplasia (n = 12), RVOT obstruction and hypoplastic pulmonary artery (n = 10). In 18/37 (49%) children, the repair of the RVOT was done without homograft. The RVOT morphology was the only indication for reconstruction with homograft. All other pre-, intra- and postoperative data were identical for both groups. There was no operative or late death. After a mean follow-up of 4.4 months, all 19 children with homograft were in NYHA class I and echocardiographic evaluation showed mild and moderate pulmonary regurgitation in 8 and 4 children respectively. Out of the 18 children without homograft, 16 were in NYHA class I and 2 in NYHA class II. Two children had early postoperative right heart failure. The mean follow-up time in this group was 5.5 months. Echocardiography revealed residual pulmonary regurgitation in 4 children, pulmonary stenosis in 6 and combined residual pulmonary valve defect in 6. If severe malformation of the RVOT or the pulmonary artery is present, a valved homograft is recommended for repair of tetralogy of Fallot. Good morphological and functional results may be achieved. PMID- 1621081 TI - [Is premedication in gastroscopy hazardous?]. AB - Premedication for gastroscopies is still controversial. Most gastroenterologists use premedication routinely, often without control of vital signs. However, even if rarely, serious (mainly cardiorespiratory) complications still occur. In 101 patients in whom a gastroscopy had been performed, oxygen saturation before, during and after the endoscopy was investigated. A fall in saturation was seen in most of the patients but was usually minor. However, severe hypoxemia occurred in some patients, especially if premedication was used. Older patients and patients with severe anemia were particularly at risk. These results emphasize that premedication should not be used without precaution and special surveillance, especially in high risk patients. Prophylactic oxygen administration significantly diminishes the risk. PMID- 1621082 TI - [Fundus plication with or without proximal selective vagotomy?]. AB - The aim of this study was to determine the influence of proximal gastric vagotomy on the outcome after fundoplication. Of 141 patients operated on for reflux disease between 1972 and 1988, 53 had fundoplication alone (group A) and 88 fundoplication combined with proximal gastric vagotomy (group B). The two groups were similar with regard to the severity of the reflux disease (esophagitis: A 69%, B 73%) but had a different incidence of concomitant ulcer disease (A 2%, B 55%). After a mean follow-up of 9 years, 111 patients (79%) were evaluated by clinical examination and 57 patients (40%) by endoscopy. Perioperative morbidity was similar (A 22%, B 19%). Successful reflux control (A and B 81%) and overall clinical outcome (Visick I and II: A 78%, B 80%) were identical. The frequency of adverse side effects was approximately the same in both groups (dysphagia: A 28%, B 26%; gas-bloat: A 52%, B 37%). We conclude that the long term results after fundoplication are not improved by additional proximal gastric vagotomy. The combined procedure is therefore only justified if both reflux disease and ulcer disease are present. PMID- 1621083 TI - Infection of Macaca nemestrina by human immunodeficiency virus type-1. AB - After observations that Macaca nemestrina were exceptionally susceptible to simian immunodeficiency virus and human immunodeficiency virus type-2 (HIV-2), studies of HIV-1 replication were initiated. Several strains of HIV-1, including a recent patient isolate, replicated in vitro in peripheral blood mononuclear cells (PBMCs) and in CD4-positive M. nemestrina lymphocytes in a CD4-dependent fashion. Eight animals were subsequently inoculated with either cell-associated or cell-free suspensions of HIV-1. All animals had HIV-1 isolated by cocultivation, had HIV-1 DNA in their PBMCs as shown by polymerase chain reaction, and experienced sustained seroconversion to a broad spectrum of HIV-1 proteins. Macaca nemestrina is an animal model of HIV-1 infections that provides opportunities for evaluating the pathogenesis of acute HIV-1 replication and candidate vaccines and therapies. PMID- 1621084 TI - Distributed neural network underlying musical sight-reading and keyboard performance. AB - Music, like other forms of expression, requires specific skills for its production, and the organization and representation of these skills in the human brain are not well understood. With the use of positron emission tomography and magnetic resonance imaging, the functional neuroanatomy of musical sight-reading and keyboard performance was studied in ten professional pianists. Reading musical notations and translating these notations into movement patterns on a keyboard resulted in activation of cortical areas distinct from, but adjacent to, those underlying similar verbal operations. These findings help explain why brain damage in musicians may or may not affect both verbal and musical functions depending on the size and location of the damaged area. PMID- 1621085 TI - Malignant hyperthermia. PMID- 1621086 TI - Scientists take one last swing. PMID- 1621087 TI - HHS cancels Gallo's moment in the sun. PMID- 1621088 TI - Do antidepressants promote tumors? PMID- 1621089 TI - Congress focuses on job discrimination. PMID- 1621090 TI - Fetal tissue. Congress considers testing Bush's plan. PMID- 1621091 TI - Researchers find organism they can really relate to. PMID- 1621092 TI - The challenge of malaria. PMID- 1621093 TI - Chance and statistical significance in protein and DNA sequence analysis. AB - Statistical approaches help in the determination of significant configurations in protein and nucleic acid sequence data. Three recent statistical methods are discussed: (i) score-based sequence analysis that provides a means for characterizing anomalies in local sequence text and for evaluating sequence comparisons; (ii) quantile distributions of amino acid usage that reveal general compositional biases in proteins and evolutionary relations; and (iii) r-scan statistics that can be applied to the analysis of spacings of sequence markers. PMID- 1621094 TI - Neurexins: synaptic cell surface proteins related to the alpha-latrotoxin receptor and laminin. AB - A family of highly polymorphic neuronal cell surface proteins, the neurexins, has been identified. At least two genes for neurexins exist. Each gene uses alternative promoters and multiple variably spliced exons to potentially generate more than a 100 different neurexin transcripts. The neurexins were discovered by the identification of one member of the family as the receptor for alpha latrotoxin. This toxin is a component of the venom from black widow spiders; it binds to presynaptic nerve terminals and triggers massive neurotransmitter release. Neurexins contain single transmembrane regions and extracellular domains with repeated sequences similar to sequences in laminin A, slit, and agrin, proteins that have been implicated in axon guidance and synaptogenesis. An antibody to neurexin I showed highly concentrated immunoreactivity at the synapse. The polymorphic structure of the neurexins, their neural localization, and their sequence similarity to proteins associated with neurogenesis suggest a function as cell recognition molecules in the nerve terminal. PMID- 1621095 TI - Fatty acid biosynthesis redirected to medium chains in transgenic oilseed plants. AB - Medium-chain fatty acids (FAs), found in storage lipids of certain plants, are an important renewable resource. Seeds of undomesticated California bay accumulate laurate (12:0), and a 12:0-acyl-carrier protein thioesterase (BTE) has been purified from this tissue. Sequencing of BTE enabled the cloning of a complementary DNA coding for a plastid-targeted preprotein. Expression of the complementary DNA in the seeds of Arabidopsis thaliana resulted in BTE activity, and medium chains accumulated at the expense of long-chain (greater than or equal to 16) FAs. Laurate became the most abundant FA species and was deposited in the storage triacylglycerols. These results demonstrate a mechanism for medium-chain FA synthesis in plants. PMID- 1621096 TI - Evidence that eukaryotes and eocyte prokaryotes are immediate relatives. AB - The phylogenetic origin of eukaryotes has been unclear because eukaryotic nuclear genes have diverged substantially from prokaryotic ones. The genes coding for elongation factor EF-1 alpha were compared among various organisms. The EF-1 alpha sequences of eukaryotes contained an 11-amino acid segment that was also found in eocytes (extremely thermophilic, sulfur-metabolizing bacteria) but that was absent in all other bacteria. The related (paralogous) genes encoding elongation factor EF-2 and initiation factor IF-2 also lacked the 11-amino acid insert. These data imply that the eocytes are the closest surviving relatives (sister taxon) of the eukaryotes. PMID- 1621097 TI - Conformation of the TAR RNA-arginine complex by NMR spectroscopy. AB - The messenger RNAs of human immunodeficiency virus-1 (HIV-1) have an RNA hairpin structure, TAR, at their 5' ends that contains a six-nucleotide loop and a three nucleotide bulge. The conformations of TAR RNA and of TAR with an arginine analog specifically bound at the binding site for the viral protein, Tat, were characterized by nuclear magnetic resonance (NMR) spectroscopy. Upon arginine binding, the bulge changes conformation, and essential nucleotides for binding, U23 and A27.U38, form a base-triple interaction that stabilizes arginine hydrogen bonding to G26 and phosphates. Specificity in the arginine-TAR interaction appears to be derived largely from the structure of the RNA. PMID- 1621098 TI - An unlikely sugar substrate site in the 1.65 A structure of the human aldose reductase holoenzyme implicated in diabetic complications. AB - Aldose reductase, which catalyzes the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of a wide variety of aromatic and aliphatic carbonyl compounds, is implicated in the development of diabetic and galactosemic complications involving the lens, retina, nerves, and kidney. A 1.65 angstrom refined structure of a recombinant human placenta aldose reductase reveals that the enzyme contains a parallel beta 8/alpha 8-barrel motif and establishes a new motif for NADP-binding oxidoreductases. The substrate-binding site is located in a large, deep elliptical pocket at the COOH-terminal end of the beta barrel with a bound NADPH in an extended conformation. The highly hydrophobic nature of the active site pocket greatly favors aromatic and apolar substrates over highly polar monosaccharides. The structure should allow for the rational design of specific inhibitors that might provide molecular understanding of the catalytic mechanism, as well as possible therapeutic agents. PMID- 1621099 TI - Harpin, elicitor of the hypersensitive response produced by the plant pathogen Erwinia amylovora. AB - A proteinaceous elicitor of the plant defense reaction known as the hypersensitive response was isolated from Erwinia amylovora, the bacterium that causes fire blight of pear, apple, and other rosaceous plants. The elicitor, named harpin, is an acidic, heat-stable, cell-envelope-associated protein with an apparent molecular weight of 44 kilodaltons. Harpin caused tobacco leaf lamina to collapse and caused an increase in the pH of bathing solutions of suspension cultured tobacco cells. The gene encoding harpin (hrpN) was located in the 40 kilobase hrp gene cluster of E. amylovora, sequenced, and mutated with Tn5tac1. The hrpN mutants were not pathogenic to pear, did not elicit the hypersensitive response, and did not produce harpin. PMID- 1621100 TI - Increased osteoclast development after estrogen loss: mediation by interleukin-6. AB - Osteoclasts, the cells that resorb bone, develop from hematopoietic precursors of the bone marrow under the control of factors produced in their microenvironment. The cytokine interleukin-6 can promote hematopoiesis and osteoclastogenesis. Interleukin-6 production by bone and marrow stromal cells is suppressed by 17 beta-estradiol in vitro. In mice, estrogen loss (ovariectomy) increased the number of colony-forming units for granulocytes and macrophages, enhanced osteoclast development in ex vivo cultures of marrow, and increased the number of osteoclasts in trabecular bone. These changes were prevented by 17 beta-estradiol or an antibody to interleukin-6. Thus, estrogen loss results in an interleukin-6 mediated stimulation of osteoclastogenesis, which suggests a mechanism for the increased bone resorption in postmenopausal osteoporosis. PMID- 1621101 TI - No requirement for p56lck in the antigen-stimulated clonal deletion of thymocytes. AB - Activation of protein-tyrosine kinases (PTKs) is required for signal transduction during T cell activation, although the pathway used during thymic selection is unknown. An in vitro system was established in which T cell receptor transgenic thymocytes underwent clonal deletion in response to peptide antigen. The effects of two PTK-specific inhibitors, herbimycin A and genistein, on the clonal deletion of immature thymocytes and the activation of mature thymocytes were examined. Clonal deletion occurred while T cell activation was inhibited and when no p56lck activity was evident. Thus, p56lck is not required for the antigen stimulated step of clonal deletion of immature thymocytes, and negative selection proceeds via a distinct pathway. PMID- 1621102 TI - In vivo calcium elevations in thymocytes with T cell receptors that are specific for self ligands. AB - Selection of the T cell receptor (TCR) repertoire in the thymus probably involves TCR-mediated signals transduced in developing thymocytes after interaction with thymic stromal cells bearing self ligands. TCR-transduced signals should have identifiable consequences that would distinguish thymocytes whose TCRs have been engaged by self ligands from those whose TCRs have not. Among thymocytes expressing a transgenic TCR of defined specificity, a large number had elevated intracellular calcium concentrations but only when resident in a negatively selecting thymus in which their self ligand was expressed. Thus, developing thymocytes are stimulated by endogenous ligands in vivo to mobilize intracellular calcium, and increased intracellular calcium concentrations may reflect the consequences of intrathymic signaling associated with thymic negative selection. PMID- 1621103 TI - [Effect of brain osmoreceptor stimulation on the function of superficial nephrons in the rat]. AB - Our previous work with lithium clearance method indicated that the diuresis and natriuresis induced by intracerebroventricular administration of hypertonic saline (icv. HS) resulted from an increase in glomerular filtration rate and a decrease in water and sodium reabsorption in the proximal tubules. In the present study, we further observed the effect of icv. HS on the glomerular filtration rate and proximal convoluted tubular and loop reabsorption in the superficial nephrons with micropuncture technique. After icv. HS, single nephron glomerular filtration rate increased from 39.6 +/- 1.9 nl/min to 48.8 +/- 2.0 nl/min (P less than 0.001), late proximal convoluted tubular fluid flow rate increased from 20.5 +/- 1.4 nl/min to 28.4 +/- 2.0 nl/min (P less than 0.01), and the ratio of tubular fluid inulin concentration to plasma inulin concentration decreased from 1.98 +/- 0.08 to 1.69 +/- 0.05 (P less than 0.01). Calculated fractional proximal convoluted tubular fluid reabsorption decreased from 49.2 +/- 2.2% to 41.7 +/- 1.8% (P less than 0.001), while calculated absolute proximal convoluted tubular fluid reabsorption did not change significantly. These results coincided with the observation with lithium clearance method. In addition, icv. HS increased absolute loop fluid reabsorption but decreased fractional loop fluid reabsorption. The present data suggest that stimulation of the brain osmoreceptor increases the glomerular filtration rate and decreases the reabsorption capacity of the proximal convoluted tubule in the superficial nephrons, both these responses result in an increase in the load of the loop of Henle with a secondary change in loop reabsorption. However, the results of the present study do not rule out the possibility that icv. HS may also inhibit the loop reabsorption directly. PMID- 1621104 TI - [Cardiovascular effect of norepinephrine in the habenular nucleus and the underlying mechanism in rats]. AB - Cardiovascular effect of norepinephrine (NE) in the habenular nucleus (Hb) and the underlying mechanism were investigated in urethane-anesthetized rats. NE microinjection into Hb produced a dose-dependent increase in mean arterial blood pressure and heart rate, an effect that could be attenuated by the pretreatment in Hb with alpha-receptor blocker phentolamine, but not by the pretreatment with beta-receptor blocker propranolol or physiological saline. Microinjection of kainic acid into Hb gave rise to a marked increase in mean arterial blood pressure and heart rate, but microinjection of lidocaine did not elicit significant cardiovascular effect. The above results suggest that NE in Hb plays an important role in cardiovascular control as a result of Hb excitation through activation of alpha-receptor. PMID- 1621105 TI - [Effect of the central noradrenergic system on carotid sinus reflex in rats]. AB - In order to study the effect of central noradrenergic system on the regulation of mean arterial pressure (MAP) by intracarotid sinus pressure (ISP), ISP-MAP relationship curves were constructed using isolated carotid sinus under the condition of injection of 6-OHDA (200 micrograms) into lateral ventricle or cauterization of locus coeruleus (LC) and compared with that obtained under the condition of control. All ISP-MAP curves can be fitted by a logistic functional plot whose characteristics can be defined by two parameters, i.e. coordinates of the inversion point of the slope of the curve and the MAP range related to the rate of change of slope factor with which carotid sinus pressure exerts its control. The results were as follows: After injection of 6-OHDA, the rate of change of the slope of the ISP-MAP curve is considerably slower than that of the normal control, thus showing a much compressed range of MAP by ISP, while the abscissa (i.e. position of ISP) of the slope inversion point of the curve shows practically no change. In comparison with the control, cauterization of LC causes a similar but less striking change of ISP-MAP curve than that of 6-OHDA injection experiment. All such differences were illustrated in Fig. 3. The above results indicated that the central noradrenergic system facilitates carotid sinus reflex and LC plays a dominant role. PMID- 1621106 TI - [Depressor effect of nucleus arcuatus stimulation in chronic stress-induced hypertensive rat]. AB - Hypertension was induced by chronic foot-shock and noise stress in adult male Sprague-Dawley rats. Microinjection of 0.3 microliters (150 mmol) sodium glutamate (Glu) into the nucleus arcuatus (ARC) elicited a significant depressor effect in rats with chronic stress-induced hypertension. The depressor effect induced by excitation of ARC neurons was attenuated significantly by microinjection of 0.3 microliters beta-endorphin antiserum (beta-EPAS) into the dorso-medial periaqueductal gray (PAG) or 0.1 microliters into the area of locus coeruleus (LC) due to blockage of beta-endorphinergic fibres from ARC to PAG or LC. PMID- 1621107 TI - [Effects of electrical cauterization of nucleus raphe magnus on gastric acid output and serum gastrin level in rats]. AB - Medullary raphe nucleus complex plays an important role in the regulation of visceral function. The effects of electrical damage of the nucleus raphe magnus on gastric acid output and serum gastrin level in anesthetized rats were observed. The experiments showed that damage of nucleus raphe magnus increased gastric acid output and serum gastrin level, which could be prevented by vagotomy but not by coeliac and superior mesenteric ganglionectomy. PMID- 1621108 TI - [Estimation of glucocorticoid membrane binding sites in synaptic plasma membrane isolated from porcine brain]. AB - Using radioligand binding assay, we measured the Bmax and Kd of glucocorticoid membrane binding sites (GCMBS) in the synaptic plasma membranes isolated from different regions of porcine brain. The Kds of GCMBS in cerebrum, cerebellum, midbrain, thalamus, nuclei caudatus and hypothalamus are all around 200 nmol/L. The Bmax of GCMBS in the mentioned brain regions ranges from 218.98 fmol/mg to 486.95 fmol/mg protein. PMID- 1621109 TI - [Effect of intraventricular injection of 6-hydroxydopamine on the initiation of hibernation in ground squirrels]. AB - The effect of forced depletion of brain norepinephrine (NE) on the onset of hibernation was observed in the ground squirrel (Citellus dauricus) by intraventricular injection of 6-hydroxydopamine (6-OHDA). The results showed: (1) Intraventricular injection of 100-200 micrograms 6-OHDA, which depleted 50-60% NE, markedly facilitated the onset of hibernation, i.e. the average induction period for hibernation in the treated animals was significantly shorter than that of the natural hibernating animals. (2) The average total torpor time in the treated animals was longer than that of natural hibernating animals. (3) All hibernating animals treated with 6-OHDA were able to wake up from deep hibernation spontaneously and undergo normal hibernation bouts. The results indicate the decrease of NE system activity in brain is one important factor in triggering the onset of hibernation. PMID- 1621110 TI - [Changes in plasma interleukin-1 and their possible relationship with the changes in glucocorticoid receptor in aged long-distance runner]. AB - For the study of the changes in plasma interleukin-1 (IL-1) and their possible relationship with the changes in glucocorticoid receptor (GR), plasma IL-1 and GR in peripheral blood leukocytes in aged long-distance runner were measured simultaneously. The activity of IL-1 was expressed as its ability to stimulate 3H TdR incorporation in the thymocytes of C57 mice. GR was determined by whole cell assay with 3H-Dex. The results showed that the activity of plasma IL-1 in aged long-distance runner was 209%, 223% and 145% of the control at 14.7-18.7, 3.8-7.0 and 1.5-2.6 KD fractions. The GR in peripheral blood leukocytes in aged runner was 65% of the control. Possible relationship between the changes in IL-1 and GR in aged long-distance runner and its physiological significance are discussed. PMID- 1621111 TI - [Protective effect of indomethacin on alloxan-induced diabetes in rat]. AB - Changes of concentration of serum glucose, insulin and glucagon induced by preadministration of indomethacin were observed in normal rats and diabetic rats induced by alloxan. The results demonstrated that the level of serum glucose in diabetic rats was lowered significantly after preadministration of indomethacin (10 mg/kg) dose-dependently. After preadministration of 5, 10, 15 mg/kg of indomethacin the level of serum glucose 48 h after injecting alloxan was decreased from the control value of 591.5 +/- 38.2 mg% to 559.1 +/- 53.2, 436 +/- 16.6 and 266.6 +/- 29.9 mg% respectively. The concentration of serum insulin was increased from the control 10.5 +/- 2.7 microU/ml to 31.9 +/- 7.0 microU/ml and glucagon from 550.0 +/- 27.0 pg/ml to 303.1 +/- 22.9 pg/ml after preadministration of 10 mg/kg indomethacin. Histologic observation showed that alloxan induced beta cell lesion in pancreatic islet could indeed be prevented by indomethacin to a significant extent. PMID- 1621112 TI - [Protective effect of verapamil against alloxan-induced damage on pancreatic islet beta-cells in rats]. AB - An experimental diabetes model was produced by intravenous injection of alloxan. Verapamil (40 mg/kg) administered intraperitoneally 30 minutes prior to alloxan was able to decrease serum glucose from 22.93 +/- 1.37 mmol/L to 8.79 +/- 0.83 mmol/L after 48 hours of injection of alloxan. Histological findings showed that the number of secretory granules in beta cells of the pancreatic islet of rats pretreated with verapamil was markedly increased as compared to rats treated with alloxan alone. PMID- 1621113 TI - Sepsis in young infants--rational approach to early diagnosis and treatment. PMID- 1621114 TI - Clinical features and haematological indices of bacterial infections in young infants. AB - The clinical features and haematologic indices of 100 young infants aged 3 months and below, admitted with suspected bacterial infections, were analysed. Fever, lethargy, hepatomegaly, poor feeding and irritability were the commonest features for suspecting a bacterial infection in these infants. However, the features significantly associated with bacterial infections were respiratory distress and cyanosis. Of the haematologic indices commonly associated with bacterial infections, only C-reactive protein and erythrocyte sedimentation rate were significantly predictive compared to leukocyte counts, absolute neutrophil counts and nitro-blue tetrazolium tests. When used in combination, a raised C-reactive protein with erythrocyte sedimentation rate, a raised erythrocyte sedimentation rate with abnormal leukocyte counts and a raised C-reactive protein with abnormal leukocyte counts were significantly associated with bacterial infections. PMID- 1621115 TI - Use of intracranial neurophysiologic recording techniques in the evaluation for epilepsy surgery in children. AB - Resective surgery is an accepted treatment modality for medically intractable focal epilepsy in children as well as in adult. During the presurgical evaluation processes, intracranial neurophysiologic recording of epileptiform abnormalities have been used much more commonly in adults and older adolescents than in infants and children. However, as infants and children are increasingly referred for early surgery in many centres, it may be necessary to study complex cases in some children with invasive electrodes in order to plan a safe and effective resection. This article gives first an overview of the rationale and indications, with case illustrations, for using these techniques. This is followed by general discussions on individual electrodes and their use in infants and children. PMID- 1621116 TI - The role of urodynamics in evaluating incontinent females. AB - A total of 84 patients had urodynamic evaluations. Twenty-two patients complained of stress incontinence, 41 patients complained of stress incontinence with other urinary symptoms and 21 complained of other urinary symptoms but not stress incontinence. Of those complaining of stress incontinence alone, 4 (18.2%) had detrussor instability, 11 (50%) had genuine stress incontinence and 7 (31%) had neither condition. Of those complaining of stress incontinence with other symptoms, 16 (39%) had detrussor instability, 19 (46.3%) had stress incontinence and 6 (14.6%) had neither condition. Of those complaining of other urinary symptoms except stress incontinence, 5 (23.8%) had detrussor instability, 3 (14.3%) had stress incontinence and 13 (61.9%) had neither condition. Urinary symptoms were found to have little correlation with the final diagnosis except for enuresis which was associated with detrussor instability. PMID- 1621117 TI - The current status of intracoronary stent: an overview. AB - Intracoronary stenting is a relatively new therapeutic interventional modality conceived to address the 2 major pitfalls of conventional balloon angioplasty, namely that of acute closure and restenosis. Much progress has been made since its clinical application in 1986. Its place amongst the multitude of novel devices currently available in the treatment of coronary obstructive disease seems secure. The challenge for investigators now is to develop a stent without the inherent problem of acute thrombosis. PMID- 1621118 TI - Neuropsychological testing: how it can benefit clinical neuroscience in Singapore. AB - Neuropsychological testing is a relatively new field in the area of clinical neuroscience. It has proven to be an effective and essential aid in the diagnostic process of brain-injured patients, especially in lesions of the cerebral cortex. More advanced countries have incorporated neuropsychological assessments in their standard neurological examinations of the brain damaged. Clinical neuropsychology is only beginning to be used in Singapore. Research using neuropsychological methods have also shown to be useful in providing a greater understanding of the brain-behaviour relationship in humans. Problems confronting the use of neuropsychological testing in Singapore are identified and the possible solutions discussed. PMID- 1621119 TI - Computerised scoring and graphing of the Farnsworth-Munsell 100 Hue test of colour vision--a program written in Pascal. AB - The Farnsworth Munsell 100 Hue test is the best test for diagnosing and assessing colour vision defects. A computer program written in Pascal which automatically scores, plots and analyses the results of the Farnsworth Munsell 100 Hue test is presented. PMID- 1621120 TI - The Mentakab Hypertension Study Project Part VI--Blood pressure measurement and hypertension: a questionnaire survey of medical staff. AB - A questionaire concerning various aspects of blood pressure measurement and hypertension was answered by 84 out of 98 (86%) doctors and 73 out of 100 (73%) nurses working in various parts of the state of Pahang. 59% and 85% of doctors and nurses respectively agreed that blood pressure should be measured routinely in all out-patients. 48% of medical staff were taught to use and 38% were actually using phase 4 as the diastolic blood pressure despite the general agreement that phase 5 should be used to denote diastolic pressure. 52% of doctors believed that hypertensive patients present with symptoms, the common symptoms cited were headache and dizziness, although it is well documented that hypertension is essentially asymptomatic. 93%, 80%, 69% and 82% of doctors believed that treatment of hypertension can prevent cerebrovascular disease, heart failure, renal failure and coronary artery disease respectively, although prevention of the last complication is yet unproven. Most doctors would begin treating a patient at rather low level of blood pressure, for example, for a man in the age group 40-49, 40% of doctors would begin drug treatment at diastolic pressure of 90 mmHg and 55% at diastolic pressure 95 mmHg. 79% of nurses and 55% of doctors were dissatisfied with the sphygmomanometer they have, the most common complaint was that the cuff-bladder 'blow up' on being inflated. PMID- 1621121 TI - Abnormalities of chromosome 11Q in three cases of acute myeloid leukemia. AB - The haematological findings and case history of 3 patients with the association of acute myeloid leukemia and translocation involving the long arm of chromosome no. 11 are presented. The recipient chromosome for the translocated material from chromosome 11 differs in all the three cases being namely chromosomes 1, 10 and 17. PMID- 1621122 TI - Clinical applications of salivary cortisol measurements. AB - The clinical applications of salivary cortisol measurements were evaluated by radioimmunoassay of time-matched saliva and plasma samples. Salivary cortisol levels of normal subjects exhibited a significant (p less than 0.001) diurnal variation with a mean (+/- SD) concentration of 8.7 +/- 4.8 nmol/L at 0800-1000 h and 2.4 +/- 1.1 nmol/l at 1500-1700 h. After an overnight dexamethasone suppression test, morning salivary cortisol levels decrease to 2.7 +/- 0.7 nmol/L (p less than 0.001 vs normal). An excellent correlation (r = 0.805) of cortisol measurements with time-matched saliva and plasma samples was obtained (y = 0.03x + 0.88, p less than 0.001, n = 91). Hypercortisolism was confirmed by raised salivary cortisols in only half of patients with elevated total plasma levels, thereby indicating that salivary cortisol measurements is a better index of adrenal status. PMID- 1621123 TI - Morbidity associated with asthma and audit of asthma treatment in out-patient clinics. AB - A study was undertaken to determine the extent of morbidity associated with asthma and to audit the management of asthma in two out-patient clinics of two district hospitals. Patients were recruited for the study during a 3-month period from December 1990 to February 1991. Seventy asthmatic patients were studied. Eighty-six percent of the patients had their sleep disturbed by asthma, 77% took daily medication regularly, 63% felt that their activities were restricted by asthma, 60% had at least one acute exacerbation in the preceding six months. Of those who had their peak expiratory flow rate (PEFR) measured, 40% had a PEFR below 50% predicted, and only 11% had normal PEFR (greater than 80% predicted). The morbidity of asthma was thus considerable. On the other hand, the drug treatment of these asthmatics was grossly inadequate. They were prescribed on average 2.1 item of drugs, which for most patients comprised an oral beta agonist and a theophylline. Only 43% of the patients received inhaler therapy, but no patients were given steroids, inhaled or oral. The drug treatment was unrelated to the severity of patients' asthma. Further, objective measurement of severity was under-used in the assessment of asthma, only 8.5% of patients ever had their PEFR recorded. This study has found that asthma is poorly managed in out-patient clinics. We need to improve the training of doctors in the optimal management of asthma. PMID- 1621124 TI - Association of diabetic autonomic neuropathy with painless myocardial ischaemia induced by exercise. AB - Silent myocardial ischaemia is now well-recognised in patients with symptomatic coronary artery disease. Its pathogenesis remains speculative, though diminished sensitivity to pain is thought to be one of the mechanisms involved. Because cardiovascular autonomic dysfunction occurs frequently in diabetic patients, we postulate that it contributes towards painless myocardial ischaemia among them. Forty consecutive diabetic (type II) male patients and ten normal volunteers were studied. Using 5 previously-validated noninvasive tests for autonomic dysfunction, 14 of these diabetic men had definite autonomic neuropathy (at least 2 abnormal tests). All 50 subjects were then exercised on a motor-driven treadmill to either exhaustion or chest pains. Thirty-three diabetic subjects were tested positive, with significant (greater than 1 mm) ST segment depression over at least 2 contiguous leads. Of these, 18 were associated with typical angina but the other 15 stopped because of fatigue or exhaustion (ie painless). Thirteen subjects who had definite autonomic neuropathy (AN+) had positive exercise ECG tests-10 had painless ischaemia, and only 3 had angina. This contrasted with 15 patients who had painful ischaemia and 5 who had painless ischaemia among the group without (AN-)autonomic dysfunction (p = 0.0047, Fisher's exact test). There were no significant differences among the various groups for peak rate-pressure-product, all subjects attaining similar maximal oxygen consumption states during which ischaemic ST segment changes were noted (painful AN+: 21917 +/- 4753; painless AN+: 20117 +/- 6752; painful AN-: 16544 +/ 4063; painless AN-: 22220 +/- 4341, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621125 TI - Male and female transsexuals: a comparison. AB - The aim of this study is to describe and compare the characteristics of 320 male and 130 female transsexuals in Singapore. The subjects were given a semistructured psychiatric interview. The results showed that the males were slightly younger, had less education and held lower level jobs. Their occupational preferences were reversed. The male transsexuals started petting, sexual intercourse and having partners about one to two years earlier, but they cross-dressed four to seven years later. Both males and females were homosexually orientated. Other studies showed that late maternal age was associated with homosexuality, but not with transsexualism. These studies also confirmed that transsexualism had its onset in early childhood, and that cross-dressing was an early feature. The Singapore 'transsexuals went through a "homosexual" and a "transvestite" phase before they became a transsexual. Western transsexuals exhibited both homosexual and heterosexual behaviour, and some were married to the opposite sex partners. Male prostitution was reported in many studies. PMID- 1621126 TI - Inflammatory myopathies. AB - Inflammatory myopathies encompass a wide range of disorders. This article deals with the idiopathic inflammatory myopathies. Classification and diagnostic criteria proposed by Bohan and Peter are still widely used. Diagnosis is based on clinical features, muscle enzyme abnormalities, electromyographic findings and muscle biopsy results. There are known associations with malignancy and lung disease which may affect the prognosis. Management consists of the prudent use of corticosteroids. In refractory cases, cytotoxic agents, cyclosporin and plasmapheresis have been used. PMID- 1621127 TI - Systemic sclerosis. AB - Systemic Sclerosis is a multisystemic disease characterized by sclerosis of the skin and visceral organs, vasculopathy (Raynaud's phenomenon) and autoantibodies. The criteria for the classification of the disease requires either proximal scleroderma (major criteria) or the presence of 2 of the 3 minor features namely sclerodactyly, digital pitting scars and bibasilar pulmonary fibrosis. There are 3 subsets of this condition--diffuse variant, limited variant (CREST syndrome) and Overlap Syndrome (where patients have features of other rheumatic diseases). There are localized forms of scleroderma and pseudoscleroderma states. The presenting features of Systemic Sclerosis are usually Raynaud's, skin changes and arthralgia. Systemic complaints like breathlessness, dyspepsia, etc depending on the organ involved may be present. Management starts with patient education regarding the disease, skin care, exercises and regular medical check-up. There is no miracle cure but much can be done to improve the quality of life of the patient. Nifedepine and other drugs may improve Raynaud's phenomenon. Drugs can be used to treat other complications. Various medication have been tested as disease modifying drugs for scleroderma. These include drugs which inhibit collagen like D-penicillamine, colchicine, and immunosupressive drugs like cyclosporin. Ketotifen, a mast cell stabilizer has been reported to be effective in scleroderma. As it is a relatively safe drug, clinical trials are underway. PMID- 1621129 TI - Tall precordial T waves: normal variant or acute myocardial infarction? PMID- 1621128 TI - Soft tissue "rheumatism" in sports. AB - Pain and stiffness of the injured region after prolonged periods of inactivity is commonly encountered following soft tissue injuries in sports. The injury in most of these instances is due to stress failure although occasionally an acute injury with a protracted course in recovery may develop similar symptoms. The most common of these condition are the enthesopathies, that include tendonitis and fasciitis, sprains and strains, bursitis, tenovaginitis and the fibrositis syndrome. PMID- 1621130 TI - A case of Dandy Walker cyst with porencephaly. AB - A 27-year-old gravida two para one mother delivered a term male baby by caesarean section. The baby was referred for enlarged head. This neonate with large head was found to have Porencephalic cyst with dilated Triventricular system. There was a posterior fossa cyst communicating with fourth ventricle. A diagnosis of Dandy Walker Cyst with Porencephaly was made. Ventriculo-Peritoneal shunt was done on the ninth day of life. The baby had an uneventful postoperative period and was subsequently discharged. PMID- 1621131 TI - A case of primary diffuse tracheobronchial amyloidosis treated by laser therapy. AB - We report a case of primary diffuse tracheobronchial amyloidosis in a 72-year-old lady who presented with a long history of recurrent cough, dyspnoea, wheezing, haemoptysis and chest infection. She was treated successfully with three sessions of laser therapy. There were improvements in both clinical symptoms and measurements of airway obstruction. Bronchodilators and oral prednisolone were not required after treatment. PMID- 1621132 TI - Primary psoas abscess: case report and review of the literature. AB - A case of primary non-tuberculous psoas abscess is reported and the literature reviewed. The aetiology of psoas abscess is varied and there is a worldwide variation in the aetiology. Primary psoas abscess is due to Staphylococcal infection. The pathophysiology, clinical features, diagnosis and treatment are discussed with emphasis on the changing pattern in the aetiology and diagnosis. PMID- 1621133 TI - Difficult intubation stylohyoid ligament calcification. AB - Intubation was difficult and traumatic in a 40-year-old patient presented for emergency oesophagoscopy because the diagnosis of stylohyoid ligament calcification was not suspected. High probability of stylohyoid ligament calcification should be suspected when there is difficulty in lifting the epiglottis and fibre-optic laryngoscopy is suggested as the best way to tackle this problem to prevent trauma and possible risk of regurgitation and aspiration especially in emergency situation. PMID- 1621134 TI - A triaxial classification of health problems presenting in primary health care. A World Health Organization multi-centre study. AB - Over the past two decades, research in a variety of countries and settings has revealed the extent to which psychological morbidity and social problems constitute an important proportion of primary health care contacts, either in their own right or in association with physical ill-health. The development of appropriate responses, medical and non-medical, to such problems is, in part, hindered by the relatively low level of awareness concerning the significance of such problems and by currently inappropriate methods of describing and classifying health care problems in the primary care setting. There is a pressing need for an appropriate, relatively simple and flexible classification or list of problems presenting in primary care. This study describes the development, under WHO auspices and in an international setting, of a triaxial classification of health problems and the testing and modification of the classification by means of an international case vignette rating exercise. A psychological problem list and a social problem list, together with detailed glossaries, suitably modified in the light of experience derived from the study, are described, and proposals enumerated of possible ways in which these lists might be further developed and used in research and clinical undertakings in primary care. PMID- 1621135 TI - Gender differences in schizophrenia in three cultures. Results of the WHO collaborative study on psychiatric disability. AB - As part of a systematic research project on the influence of gender factors on age at onset, symptomatology, and course of schizophrenia, data on gender differences in age at onset and symptomatology of schizophrenia from the WHO Collaborative Study "On Assessment and Reduction of Psychiatric Disability" were compared between seven research centres of three different cultural regions. Results on age at onset of five European centres confirmed the well known fact of an earlier onset in men. The earlier onset in women seen in Khartoum and Ankara could be attributed to patient selection because male/female differences in age at onset and male/female ratios in the various samples covary. In the Islamic centres no relevant gender differences in real age at onset and in symptomatology could be detected as probable causes of earlier hospitalisation of women. Major gender differences in symptomatology were found in the Balkan centres of Sofia and Zagreb with a high prevalence of delusional symptoms in women and depression in men. In Western Europe centres, nuclear schizophrenic symptoms were equally prevalent in either sex, while nonspecific symptoms like irritability and tiredness (more frequent in women) and maladaptive illness behaviours like alcohol abuse and social withdrawal (more frequent in men) differed between the sexes. Explanatory hypotheses and the implications of these results are discussed. PMID- 1621136 TI - Is age of onset in schizophrenia influenced by marital status? Some remarks on the difficulties and pitfalls in the systematic testing of a "simple" question. AB - Schizophrenia is a disease characterized by a distinctly higher age at onset and at first admission in females than in males. In a systematic study on gender differences in schizophrenia we have confirmed this finding using different sets of data, in particular through the examination of a large and representative sample of first-admitted patients. The question addressed in this paper is whether marital status influences this sex-specific age difference. Assuming that marriage or a stable relationship is a protective factor in schizophrenia, delaying the onset of the disease or first hospitalization, the hypothesis was formulated that the later age of onset in women is at least partly explained by their generally earlier age of marriage. Testing this hypothesis illustrates some of the methodological problems that often occur when a causal analysis of social data is attempted. The problems emerge especially when both the dependent variable (age of onset/first admission) and the independent variable (marital status) are essentially related to age. First results appearing to indicate an influence of marital status on age at first admission did not bear a critical interpretation. PMID- 1621137 TI - Social outcome in schizophrenia: a 13-year follow-up. AB - The cohort consists of all psychiatric patients (n = 53) admitted for the first time in 1972 from a well-defined catchment area with a population of 582,000 inhabitants aged 15 years and over. Furthermore, they were all registered with the diagnosis schizophrenia in the nation-wide psychiatric register at least once during an observation period from the day of the first admission in 1972 until August 31, 1983. The entire cohort was followed up on average 13 years after their first admission. Poor employment outcome (79%), poor social contact outcome (55%), and poor overall social outcome (76%) characterized the living conditions of the 42 patients alive at follow-up. Good employment outcome was predicted by "born in rural area." Good social contact outcome was predicted by full remission at first discharge and poor outcome by male sex. Good overall social outcome was predicted by "born in rural area" and of marginal significance by high social status at first admission. A comparison of parents' highest social group and patients' social group at follow-up supports previous findings on social drift. PMID- 1621139 TI - The high incidence of psychiatrically treated disorders in the inner city of Mannheim. Susceptibility of German and foreign residents. AB - In earlier investigations in the city of Mannheim we examined the spatial distribution of the incidence of treated mental disorders in 1965 and 1974-80. In studying the ecology of psychiatric disorders over time, it is important to consider major demographic developments. In Mannheim between the mid-sixties and 1980 the most striking demographic change was the increase of foreign residents, whose proportion almost trebled during this period. In this study we test the hypothesis whether the excess morbidity in the inner city where housing conditions are relatively poor and the percentage of foreign residents is far above average can be explained by the high proportion of immigrants, mainly from Turkey, living there. Due to motivational and administrative factors, most immigrant workers being recruited on the basis of good physical and mental health, the age-adjusted incidence of treated psychiatric disorders between 1974 and 1980 among the German population exceeded that of foreign residents. The high concentration of psychiatric disorders in the inner city is due solely to the German and not to the foreign residents. The most plausible explanation for this is provided by the segregation hypothesis. Individuals with vulnerable personalities tend to move to socially disorganized districts of the city. Furthermore, the health status of those Germans who left areas of poor environmental conditions was probably better in comparison to those who remained in the inner city. PMID- 1621138 TI - Center differences and cross-national invariance in help-seeking for panic disorder. A report from the cross-national collaborative panic study. AB - Help-seeking behaviour for treatment of panic disorder was investigated in the sample of the Cross-National Collaborative Panic Study Second Phase. A total of 1168 patients were entered into this trial in 14 countries. Although there were significant center differences in prior treatment and utilization of health services there were also similarities. Treatment had been provided mainly by general practitioners. Drug treatment consisted mostly of prescription of classical tranquilizers and had a longer duration than treatment by psychotherapy. Patients with agoraphobic avoidance, past major depression and longer duration of illness used medical and psychiatric treatment facilities more intensely. Older and more severely disabled subjects were more frequently treated by medical health care providers and were more likely to receive psychotropic drugs. The results indicate that general practitioners carry an important load in the treatment of panic disorders but may need more information about recent development in pharmacotherapy for this condition. PMID- 1621140 TI - A psychiatric unit in a general hospital in Brazil: predictors of length of stay. AB - The planning and organization of mental health care in developing countries frequently lacks empirical data. The World Health Organization recommended psychiatric brief inpatient programs in general hospitals for these countries as a cost-effective alternative to the traditional mental hospital. Length of hospital stay is a crucial factor in a cost-effective mental health care organization. In a newly organized psychiatric inpatient unit in a general teaching hospital in Brazil we investigated the influence of 16 socio-demographic and clinical variables on the length of stay. Distance from residence to hospital (P less than 0.10), clinical diagnosis (P less than 0.05) and religious affiliation (P less than 0.05) were significantly related to length of stay. Possible mental health care implications of this short stay program are discussed. PMID- 1621141 TI - Influence of having a hospitalized mentally ill member in the family on attitudes toward mental patients in Turkey. AB - The influence of having a mentally ill member in the family on various attitudes was assessed. An exposed group (those having a mentally ill member) was compared with a no-exposure group. The attitudes assessed toward two vignettes included recognition of mental illness, social distance, expected burden, expected influence on one's health, treatment choice, and prognosis. The total sample consisted of 84 subjects selected from the family members of patients from psychiatric (exposed) and other (no-exposure) clinics. Direct experience with a mentally ill family member did not make a significant difference in the attitudes toward the vignettes, but the type of psychopathology did. The results were discussed within the context of findings from Western cultures. PMID- 1621142 TI - Patients in the care of private psychiatric practitioners. Comparison with public hospital patients and the background districts' population. AB - In Western societies, the number of psychiatric hospital beds has decreased markedly in the past decades. The reduction in hospital beds has resulted in a relatively large number of mentally ill individuals residing in the community. They experience varying degrees of success. One form of treatment available to such patients is private psychiatric consultation. In Denmark and England (two countries with public supported health care systems) the number of psychiatrists in private practice (PPPs) has increased in recent years. These private practioners may offer a mode of treatment which may meet the needs of a subgroup of the psychiatric patients in the community. The fees of the PPPs are paid by the National Health Service. In this study we report on the characteristics of the patients attending the consultation of private psychiatrists and the treatment which they are offered. We compare the patients of the PPPs with 1. psychiatric patients residing in the same districts who are cared for by the public hospital system and 2. the background populations of these same districts. The results suggest that the patients in private psychiatric practice are distinct in a number of ways. Neurosis is the dominant diagnosis. Of the patients, 71% are women; the patients tend to be younger than the background districts population; after controlling for age, the marital status of the patients in PPPs' care does not differ significantly from that of the background population, and they are comparable to the background population in level of employment. These patients are more able to care for themselves than the psychiatric patients treated in the public hospital system. The results suggest that PPP is a means of caring for a subgroup of the psychiatric patients in urban settings. PMID- 1621143 TI - Cervical spine motion in the sagittal plane. II. Position of segmental averaged instantaneous centers of rotation--a cineradiographic study. AB - Anteflexion and retroflexion movements of the cervical spine were recorded cineradiographically during three measuring sessions to determine reproducibility as well as intraindividual and interindividual variability of segmental instantaneous centers of rotation (recorded as "averaged" and "standard"). Segmental averaged instantaneous centers of rotation were based on data obtained from all frames of the cineradiographic film by the use of the average pentagon and moving average method. Only the first and last frame were used to construct the segmental standard instantaneous centers of rotation. Contrary to segmental range of motion, a parameter of quantity of motion, the position of the averaged instantaneous centers of rotation (better than the standard), a parameter of quality of movement, shows a variability of such low extent that it seems feasible to use it to diagnose abnormal mobility or in assessing therapy in the neck region. PMID- 1621144 TI - Radiologic evaluation of dens fracture. Role of plain radiography and tomography. AB - A retrospective study of 50 dens fractures was performed. In 47 of 50 cases (94%), plain radiographs disclosed the fracture. Initial cross-table lateral view alone showed the fracture in 43 cases. In the remaining four cases, routine plain films revealed the fracture: open-mouth view in three cases and lateral skull view in one case. In 3 of 50 cases (6%), plain films were negative, and fractures were seen only on tomography. Conventional circular tomography was performed in 26 cases; results were divided into 3 categories according to the significance of the findings: Category I, tomography confirmed plain radiographic findings, but added no further information; Category II, tomography detected additional findings or showed the extent of injury better than plain radiography; Category III, fracture was only seen by tomography. There were 19 cases in Category I, 4 in Category II, and 3 in Category III. Careful evaluation of plain radiographs remains the primary method for diagnosis of dens fractures. Tomography should be performed whenever plain radiographs or clinical symptoms are suspicious for dens fracture. In addition, tomography is useful to define the fracture level and pattern, which are important factors in the management of these injuries. PMID- 1621145 TI - Biomechanical evaluation of four different posterior atlantoaxial fixation techniques. AB - Four different techniques for posterior atlantoaxial fusion were tested in vitro: 1) wire fixation with one median graft (Gallie type); 2) wire fixation with two bilateral grafts (Brooks type); 3) transarticular screw fixation (Magerl); and, 4) two bilateral posterior clamps (Halifax). The experiment was designed to determine the immediate three-dimensional stability of the spinal construct. Ten fresh human cadaveric specimens were tested intact, injured, and instrumented with each of the fixation techniques. The injury consisted of a severe soft tissue injury model, in which the alar, transverse, and capsular ligaments were transected. The three-dimensional motions of C1 relative to C2 were measured as the specimens were subjected to loads of pure moments in flexion-extension, axial rotation, and lateral bending. Each fixation technique significantly decreased motion in all directions, as compared to the intact and injured spines. We found that the Gallie system generally allowed significantly more rotation in flexion, extension, axial rotation, and lateral bending than the other three fixation techniques. There was generally no significant difference between the amount of rotation with the other three fixation techniques. However, the Magerl technique tended to allow the least rotation. The anteroposterior translation of two points on C1 were about equal for all fixation techniques. PMID- 1621146 TI - Expansive laminoplasty with reattachment of spinous process and extensor musculature for cervical myelopathy. AB - Since 1986 we have performed expansive laminoplasty with reattachment of the spinous processes and extensor musculature in cases of cervical myelopathy, to avoid the late postoperative complications of extensive laminectomy. The operative procedure and results are given in detail. Forty cases (24 men, 16 women) were followed for a mean of 28 months. Postoperative results were satisfactory, with no major complications according to the evaluation criteria of the Japanese Orthopaedic Association. No instability or malalignment was seen on postoperative radiographs. PMID- 1621147 TI - Effects of altering core body temperature on somatosensory and motor evoked potentials in rats. AB - The effects of core temperature on three potentials--somatosensory spinal evoked potential, somatosensory cortical evoked potential, and spinal motor evoked potential--were studied in rats. Hyperthermia reduced the latency and increased the conduction velocity of all three potentials. Somatosensory spinal evoked potential amplitude was unchanged, whereas somatosensory cortical and spinal motor evoked potentials deteriorated above 42 C. Hypothermia increased latency and decreased conduction velocity in all three potentials. The amplitude of the spinal motor evoked potential decreased, and the somatosensory cortical and spinal motor evoked potentials disappeared below 28 C. Hyperthermia and hypothermia caused significant changes in the latency of all three potentials. The latency change of all three potentials became significant at 2-2.5 C above or below baseline, suggesting a range within which evoked potential studies should be performed. PMID- 1621148 TI - "Backfiring" in spinal cord monitoring. High thoracic spinal cord stimulation evokes sciatic response by antidromic sensory pathway conduction, not motor tract conduction. AB - Spinal cord stimulation has been advocated as an alternative to motor cortex stimulation for motor tract activation. To test this theory, evoked responses were recorded from lumbar spinal cord (L2; n = 14), spinal roots (L4-L7; n = 112), peripheral nerves (sciatics; n = 28), and hind limb muscles (n = 28) after epidural stimulation of the T1-T2 segment of the spinal cord in dogs (n = 12), cats (n = 2), and monkeys (n = 2). The spinal response evoked by spinal cord stimulation was resistant to a dorsal hemisectioning (depth, 7-8 mm) of the midthoracic spinal cord. A minimal attenuation of latency and amplitude occurred with dorsal hemisectioning, suggesting signal transmission through descending or ascending pathways in the ventrolateral and ventral quadrants of the spinal cord. The sciatic nerve response was abolished by a dorsal column transection (depth, 3 4 mm) or ipsilateral lumbar dorsal rhizotomy (four dorsal roots). This shows that the evoked response recorded from the sciatic nerve in our animals was not travelling, as we expected, through the ventral roots, but rather was conducted antidromically through sensory fibers in dorsal roots. PMID- 1621149 TI - The use of instant moire photographs to reduce exposure from scoliosis radiographs. AB - A total of 258 patients with some degree of idiopathic scoliosis was monitored with both radiographs and moire photography to determine the degree of progression of spinal curvature. The use of polaroid photography to document moire fringe patterns proved to be a rapid and useful process for placing an instant photographic record in patient charts while conducting routine physical examinations. Standardization of procedures for making and evaluating moire photographs reduced patient exposure to X-rays. PMID- 1621150 TI - Measurement error in assessment of vertebral rotation using the Perdriolle torsionmeter. AB - The Perdriolle torsionmeter assesses vertebral rotation on a spinal radiograph. It is frequently used to measure improvement in spinal derotation following Cotrel-Dubousset instrumentation for scoliosis. In this study, intraobserver and interobserver measurement error was examined during use of the torsionmeter. Intraobserver error was as follows: 53% of the measurements were accurate to within 5 degrees, and 21% erred greater than 10 degrees. Error from the actual value averaged 6 degrees. Interobserver error was as follows: Among six observers, only one third of the radiographs had measurements within 5 degrees of each other. Another one third erred by more than 10 degrees. Because of this significant intraobserver and interobserver error, precise measurements of rotation using the torsionmeter cannot be expected. Efforts to quantify spinal derotation with the torsionmeter after Cotrel-Dubousset instrumentation may not be valid. PMID- 1621151 TI - Diagnostic findings in painful adult scoliosis. AB - The purpose of this study was to document the diagnostic findings in a group of adult patients presenting with both scoliosis and pain. Fifty-five adults were evaluated by medical history, physical examination, radiography, myelography followed by computed tomography, discography followed by computed tomography, and single- and dual-photon densitometry. Curves were 49% adult degenerative onset, 44% idiopathic. The older degenerative patients had myelographic defects most commonly within the primary curve and multiple abnormal, not necessarily painful, discs throughout the lumbar spine on discography. The idiopathic group had myelographic defects most commonly in a compensatory lumbar or lumbosacral curve. On discography, all idiopathic patients had at least one abnormal, painful disc, and 88% had their pain reproduced. Pain-producing pathology was frequently identified in areas that would not have been included in the fusion area according to accepted rules for treatment of idiopathic scoliosis. PMID- 1621152 TI - Scoliosis Research Society. Multicenter spine fracture study. AB - This study consisted of 1,019 spinal fracture patients followed prospectively for 2 years. Sixty-four physicians from 12 countries participated. The purpose of the study was to determine: 1) the relationship between neurologic deficit and fracture type, level, and spinal canal compromise; 2) the neurologic outcome comparing surgical versus nonsurgical treatment and anterior versus posterior surgery; and 3) the relationship of pain to both kyphotic deformity and to surgical and nonsurgical treatment. The main findings of this study are as follows: 1) seat belts reduced the incidence of severe neurologic injury; 2) there was a higher incidence of neurologic deficit with fracture-dislocations and a higher incidence of neurologically intact patients with compression and flexion distraction injuries; 3) there was a greater incidence of complete neurologic deficits caused by fractures at the spinal cord level, and a diminished incidence at the cauda equina level; 4) for burst fractures there was a weakly positive relationship between canal compromise and neurologic deficit, including bladder function; 5) surgical intervention led to a greater percentage of improved neurologic function than nonoperative treatment, but the rate of improvement was not statistically different; 6) anterior surgery was not more effective than posterior surgery in improving the neurologic function when function was assessed using the Frankel or Motor Index scales, but it was statistically significant when compared to the Manabe scale; 7) in patients who deteriorated before surgery and underwent surgery, there was a greater improvement neurologically, particularly for anterior surgery, compared to those patients treated nonoperatively or to the overall surgically treated group; 8) There was a statistically significant relationship between bladder function and fracture type, with an increased incidence of absent function seen with fracture dislocations, of impaired function with burst fractures, and of intact bladder function with compression and flexion-distraction injuries; 9) anterior surgery was more beneficial in improving complete bladder impairment to partial impairment compared to posterior surgery; 10) a kyphotic deformity of greater than 30 degrees at 2-year follow-up was associated with an increased incidence of significant back pain; 11) patients who had surgery complained less of severe pain than those who were treated without surgery. PMID- 1621153 TI - Magnetic resonance imaging of trauma to the thoracic and lumbar spine. The importance of the posterior longitudinal ligament. AB - Magnetic resonance imaging was used to evaluate 24 patients with injuries to the thoracic, thoracolumbar (T12-L1), or lumbar spine. Correlation of the magnetic resonance imaging findings to surgical therapy and outcome was evaluated, with particular attention to the longitudinal ligaments. The ability of the magnetic resonance imaging to detect the extent of trauma to the spinal cord parenchyma and to the anterior and posterior longitudinal ligaments was found to be important in guiding the surgical approach to these spine fractures. PMID- 1621154 TI - Junctional burst fractures. AB - Twenty-two patients with burst fractures in this mechanically and neurologically distinct region (T11-L2) were studied at injury and after acute surgical reduction and stabilization (antikyphosis and ligamentotaxis concept). Canal compromise averaged 42% (10-82%) before surgery, and at follow-up 14% (0-46%), segmental kyphosis 15 degrees (4 degrees-27 degrees) and 3 degrees (0 degree-15 degrees), and vertebral segment height 62% (41-85%) and 86% (60-100%), respectively. Incomplete patients gained an average of 1.8 Frankel subgrades. The described treatment can predictably recanalize the spine, correct deformity, and stabilize neurologic compromise. A significant correlation between postoperative neurologic status and the radiographic criteria under study could not be established. PMID- 1621155 TI - Canal clearance in burst fractures using the AO internal fixator. AB - The purpose of this study was to evaluate the ability of posterior distraction delivered by the AO internal fixator to effect a satisfactory reduction of the intraspinal fragments in burst fractures. The overall decompression achieved was from an initial compromise of 54% to a residual encroachment of 40%. Canal clearance proved most effective when carried out in the first 4 days, with an initial canal compromise of between 34 and 66%. The extent of improvement, even in this group, was not dramatic, with an average of 31% encroachment still remaining, with some cases as high as 50%. Therefore, we recommend that when canal clearance is essential, anterior decompression is the treatment of choice. PMID- 1621156 TI - Percutaneous needle biopsy of the spine. AB - The results of 75 percutaneous needle biopsies of the spine were analyzed. There were 8 cervical, 25 thoracic, 27 lumbar, and 15 sacral biopsies. An accurate diagnosis was made in 92% of all cases. Metastatic disease yielded the best accuracy rate (96%). The lowest accuracy rate (82%) was noted with benign primary tumors and fractures. The results were better in female patients than male (97% vs. 86%). Larger needles gave slightly better accuracy (97%). No relationship between accuracy and spine level was found. There were two complications: one pneumothorax and an episode of self-limited hemorrhage. Percutaneous needle biopsy is a safe and reliable method of obtaining a diagnosis in many different spine lesions. PMID- 1621157 TI - The use of freeze-dried fibular allograft in anterior cervical fusion. AB - Eighty-three segmental fusions were performed on 42 patients who underwent anterior cervical discectomy and fusion with freeze-dried fibular allograft for cervical spondylosis. Fusions were carried out over one to four levels. The mean follow-up period was 22.1 months (range, 9-47 months). The patients had both clinical and radiographic follow-up. Eighty-eight percent of the patients were found to have excellent or good clinical results. Radiographic follow-up revealed that 92% of the grafts obtained complete or partial union by 6 months after surgery. Forty patients were shown to be radiographically stable on lateral flexion and extension films by 8 weeks after surgery. The use of freeze-dried fibular allograft is a safe and efficacious procedure. PMID- 1621158 TI - Lumbar facet joint asymmetry. Intervertebral disc herniation. AB - A study of 136 patients with lumbar intervertebral disc herniation was undertaken to test the hypothesis that asymmetry of the facet joints is associated with the level, type, and side of herniation. Fifty cases of central herniation and 86 cases of lateral herniation, all at the L4-5 or L5-S1 levels, were studied by computed tomographic scans. Adjacent (nonherniated) levels were used as controls. The facet joint angles were measured at the L4-5 and L5-S1 levels of the control, central, and lateral herniated levels. The results showed a similar degree of facet joint asymmetry at all levels. In cases of lateral herniation, there was a significant difference in the facet angle between the herniated and nonherniated side at the L5-S1 level, but not the L4-5 level. The mean difference, however, was less than 3 degrees and not considered to be clinically relevant. There was no difference in the distribution of the more coronally or sagittally facing facet joints with respect to the side of lateral herniation. These results do not support the hypothesis that facet asymmetry is associated with lumbar intervertebral disc herniation. PMID- 1621159 TI - The Luque trolley revisited. Review of nine cases requiring revision. AB - This study is a retrospective review of nine patients who underwent Luque instrumentation without fusion from 1982-1984. Average age at surgery was 9 years. Average preoperative curve was 51 degrees (30 degrees-70 degrees). All nine patients have had at least one revision. All of the revisions were technically difficult secondary to extensive fibrosis and weakened laminar bone. Spontaneous fusion was documented in all nine patients, limiting further correction. Final follow-up curves averaged 51 degrees (25 degrees-90 degrees). Average gain in spinal height was 5.8 cm (2.3 in) but only a small portion was derived from the instrumented levels. Segmental spinal instrumentation without fusion in immature patients was not effective in control of spinal deformity, nor did it allow anticipated growth under the instrumented regions. PMID- 1621160 TI - Latent psoas abscess after anterior spinal fusion. AB - This case is presented to emphasize that late infection should be considered in all postoperative patients as a cause of pain. A psoas abscess may remain dormant for many years after an anterior spinal procedure. It should be considered in the differential diagnosis of back pain and lumbar radiculopathy after anterior spinal fusion. The lumbar nerve plexus lies within the psoas muscle, and referred pain patterns may occur in the lumbar nerve distribution. In this case, dysesthesias occurred in the distribution of the genitofemoral nerve. The diagnosis and treatment of a psoas abscess has been greatly aided by use of CT and ultrasound. Either of these modalities may be used for directed percutaneous drainage of the abscess. The presence of metal fixation devices necessitates removal of the hardware in order to ensure eradication of the infection. PMID- 1621161 TI - Spinal epidural abscess as a complication of duodenolumbar fistula. A case report. AB - The characteristic delay in diagnosis and treatment of spinal epidural abscess of unusual presentation in a patient with significant comorbidities often results in permanent neurologic deficits. Fortunately, in the case reported here, the patient made a complete recovery. Rapid diagnosis and intervention are essential, because degree of recovery is proportional to the extent of the neurologic deficit present before surgery. PMID- 1621162 TI - The use of dynamic magnetic resonance imaging to identify cervical spine disc herniation and cord compression. A case report. PMID- 1621163 TI - Brown-Sequard syndrome and herniated cervical disc. PMID- 1621164 TI - Unilateral blindness as a complication of patient positioning for spinal surgery. A case report. AB - Extreme care must be used in positioning patients for surgery in a prone position. A padded Mayfield headrest may not be appropriate for all patients undergoing spinal surgery, as exophthalmus or a flattened nasal bridge may allow transmission of pressure to the globe. Our current approach is to use supplementary foam rubber support, with repeated, meticulous attention to keeping the eyes free from all pressure. Finally, unexplained intraoperative occurrence of a bradyarrhythmia or conduction disturbance may signal increased intraorbital pressure during general anesthesia. PMID- 1621165 TI - Unusual sign of a Jefferson fracture. A case report. PMID- 1621166 TI - Migraine. PMID- 1621167 TI - Rural medicine--a specialty in its own right? PMID- 1621168 TI - Findings and implications from research on student learning. AB - This paper sets out a number of important conclusions drawn from research on student learning in higher education. Although there is an emphasis on medical education, most of the research conclusions presented are relevant to undergraduate education in general. The conclusions and accompanying questions are intended to promote debate among academic practitioners and students on how to improve the quality of student learning. In conjunction with the complementary research review by Entwistle on how departments may influence the quality of student learning, the conclusions and questions presented here formed the basis of a workshop presented at the 1991 Conference of the South African Association for Medical Education held at the University of Cape Town. PMID- 1621169 TI - Influences on the quality of student learning--implications for medical education. AB - This paper reviews recent research into the ways in which departments influence the quality of student learning. A substantial literature has developed which describes differences in the ways in which students learn and study in higher education. These differences emphasise the distinction between seeking personal understanding and reproducing information or procedures. The research indicates that certain departments, and some lecturers, are much better than others in encouraging students to look for deep levels of meaning. The quality of teaching and the methods of assessment are particularly influential, but so is the extent to which students are helped to develop effective studying and learning strategies. Some students have been shown to have major problems in the way they perceive and utilise the opportunities for learning provided by departments. While much of the research is not drawn directly from medical faculties, the relevance to medical education is pointed up and supported by specific examples of relevant research. PMID- 1621170 TI - Dermatoses in the canning industry--the roles of glove use and non-occupational exposures. AB - Primary prevention is the mainstay of management of occupational dermatoses. Despite the high rates of dermatoses found in a study of 686 female workers in a canning factory in March 1990, use of protective gloves was extremely low, even though there was evidence that they prevented acute paronychia and intertrigo. Reasons associated with low glove use were unavailability, discomfort and workers' failure to perceive a protective role for gloves. Difficulties with replacement of damaged gloves were an important cause of unavailability. Domestic and other non-occupational exposure at the workplace appeared to be unimportant in the development of dermatoses. Important preventive interventions are possible in the industry to reduce the rates of dermatoses among the workforce. PMID- 1621171 TI - Collagenous colitis--a rare cause of chronic watery diarrhoea. A case report. AB - Collagenous colitis is a clinicopathological syndrome occurring predominantly in middle-aged females presenting with chronic watery diarrhoea. Histologically the disorder is characterised by a mononuclear cell mucosal inflammatory infiltrate and subepithelial collagen thickening. The condition was first described in 1976 and since then approximately 100 cases have been reported in the literature. We present here the first reported case of this rare disorder in South Africa. PMID- 1621172 TI - Membranous lipodystrophy. Clinical and electrophysiological observations in the first South African case. AB - A 37-year-old white man with membranous lipodystrophy (ML), the first case from Africa, is reported. Two years before presentation a diagnosis of presenile dementia of uncertain aetiology had been made. The diagnosis of ML was confirmed on histological examination of bone fragments obtained during surgery for reduction of pathological fractures. Computed tomography of the head showed typical cerebral atrophy and basal ganglia calcification. Electrophysiological observations included normal peripheral and central conduction studies. PMID- 1621173 TI - Acute benign pulmonary histoplasmosis--comparative costs of management. PMID- 1621174 TI - SimpliRED--a rapid and reliable test for HIV. PMID- 1621175 TI - Hepatic sinusoidal fibrosis associated with the use of cytotoxic drugs. PMID- 1621176 TI - Biopsy technique can influence treatment outcome in head and neck cancer. PMID- 1621177 TI - [Lymphomas in the acquired human immunodeficiency syndrome. Clinical, histological, immunological, and developmental study of 26 patients]. AB - PURPOSE: To assess in a retrospective fashion the appearance of lymphoid malignancies in subjects infected by the human immunodeficiency virus, or included in any risk-group, between January 1984 and June 1991. MATERIAL AND METHODS: Twenty-six patients with AIDS-related lymphoma (23 non-Hodgkin's lymphoma (NHL) and 3 Hodgkin's disease (HD) cases) were entered in the study. Of them, 25 were males, with a mean age of 27 years. Eleven were intravenous drug abusers, eight were homosexuals, five were haemophiliacs and two were heterosexuals. RESULTS: The NHL histologic subtypes found were: small, non cleaved cell (Burkitt's), 14 cases; immunoblastic, 2 cases; diffuse, large cell, 1 case; anaplastic, 1 case; extramedullary plasmacytoma, 1 case, and high grade, unclassifiable, 4 cases. The malignant cell immunophenotype was B in 95% of the cases. The pathological stage at diagnosis was IV-B in 16 cases, IV-A in 3, III-B in 1 and I-E in 3. Extranodal involvement was seen in 95% of the patients, mainly extended to the bone marrow (53%), liver (48%) central nervous system (35%) and digestive tract (22%). The three HD patients (2 with lymphocytic depletion and 1 with mixed cellularity) were in stage IV-B at diagnosis, with bone marrow involvement. Twenty-three patients received chemotherapy, 7 were treated with radiotherapy, and 4 underwent surgery. Complete remission (CR) was attained in 35% of the cases and partial response in 55%. The median survival of the series is 7 months, and that of the CR patients is 20 months (p less than 0.001). The series mortality was 77%, mostly related to disease progression or opportunistic infection. CONCLUSION: The general characteristics of AIDS-related lymphoma were confirmed here: aggressive clinical course, poor response to therapy and high risk of opportunistic infections. The possibility of achieving CR may justify the use of combination chemotherapy in patients with good functional status. PMID- 1621178 TI - [Pernicious anemias with subtle or atypical presentation]. AB - PURPOSE: To assess the prevalence and clinico-biologic characteristics of pernicious anaemia (PA) showing subtle or atypical onset. MATERIAL AND METHODS: One-hundred and twenty-four patients were found to fulfill criteria for PA (serum vitamin B12 deficiency due to absence of intrinsic factor secretion because of severe gastric atrophy). Of them were disclosed those lacking macrocytosis (MCV less than 98 fL), with or without anaemia (Hb less than 120 g/L in women and less than 14 f/L in men), but showing decreased serum B12 rates (less than 150 pmol/L). RESULTS: Macrocytosis was absent in 15 out of the 124 cases (12.1%); either they had anaemia or not, serum B12 rates were decreased in all cases. Eight patients had concurrent iron deficiency, one had secondary anaemia, two had polycythaemia and four were normal from a haematological standpoint. Serum B12 assays were performed because of neuropsychiatric impairment (2 cases), polycythaemia study (3 cases), or positive anti-parietal cell antibodies found in an immunologic study (4 cases). The remaining patients were studied for chronic atrophy of the gastric mucosa (2 cases), and Plummer-Vinson syndrome, leucopenia and nutritional assessment (1 case of each condition). CONCLUSIONS: Atypical presentation of pernicious anaemia, whose frequency is probably underestimated, was confirmed in our environment. This condition must be suspected and ruled out in patients with characteristics similar to those described above. PMID- 1621179 TI - [Possible immunological effects of transfusion in the cancer patient]. PMID- 1621180 TI - [Hematological repercussions of human immunodeficiency virus infection and their treatment]. PMID- 1621181 TI - [Cytogenetic marker del(12p) in a case of acute myeloid leukemia M4 with eosinophilia and inv(16)]. AB - A 35-year-old Spanish female having acute myelomonocytic leukaemia with marrow eosinophilia is reported. The karyotype revealed the specific chromosomal abnormality associated with this disorder, inv(16), and a less-specific myelodysplastic cytogenetic marker, del(12p). We have reviewed the published cases in order to elucidate the possible significance of presenting a 12p deletion (nonrandomly associated with chronic myelomonocytic leukaemia) together with other chromosomal rearrangements. PMID- 1621182 TI - [In vitro formation of fibroblast colony-forming units in the bone marrow of patients with solid malignant tumors]. AB - The number of bone marrow fibroblast colony-forming cells (CFU-F) were studied in twelve healthy donors, four colon (CP) and nine lung cancer patients (LP). A liquid culture system has been used to characterize human bone marrow CFU-F. The results showed any recognizable CFU-F in three patients with colon cancer and in two patients of the other group. One of the four CP and five of the nine LP presented a CFU-F value of 17 and 2, 8, 22, 29, 32, respectively compared to 65 from normal subjects. Two LP reached normal CFU-F values (normal range = 33-191). These data support the conclusion that the 84.6% of these solid tumor cancer patients study produced less number of proliferative status of fibroblast colony forming cells. PMID- 1621183 TI - Familial thrombotic thrombocytopenic purpura in a Bedouin family. AB - A 24-year-old Beduin pregnant woman in her 22nd week of gestation was treated successfully by plasmaphereses and steroids as soon as the diagnosis of TTP was confirmed by the clinical and laboratory criteria needed. Her sister died due to complications of TTP in pregnancy five years earlier while her other sister recuperated from TTP during pregnancy. However, fetal loss ensued. Thus, family history in pregnant women presenting with toxemia of pregnancy--like--syndrome may be the first clue to familial TTP. PMID- 1621184 TI - [Meningeal myelomatosis. Presentation of a case]. AB - The case of a 36-year old man with IgA kappa multiple myeloma in whom meningeal myelomatosis developed is reported, and a brief review of previously published cases is made. Meningeal involvement develops in patients with high tumoral mass myeloma. Because of its poor prognosis, central nervous system chemoprophylaxis based on clinical and cerebrospinal fluid data, and systemic treatment according to severity, is suggested. PMID- 1621185 TI - [Seroprevalence of antibodies against Plasmodium falciparum in volunteer donors from various cities in Venezuela]. AB - The prevalence of antibodies to Plasmodium falciparum was studied in 890 blood donors from different geographical areas of Venezuela. The overall prevalence, as established by ELISA, was (1.7%). Seropositivity was higher in those samples obtained in Sucre (2.5%) and Apure (1.7%) states both with foci of malaria transmission. It is proposed that medical history should be reinforced by screening antimalarial antibodies in donors at risk. PMID- 1621186 TI - [Cavernous hemangioma of the spleen with a localized intravascular coagulation syndrome (Kasabach-Merritt syndrome). Ultrastructural study]. AB - Haemangioma is the commonest non-malignant tumour of the spleen. Cytopenia and coagulopathy, secondary to cell trapping and coagulation factors consumption inside the haemangioma, respectively. May occasionally occur as accompanying phenomena. A woman is presented who had splenic haemangioma associated with leucopenia and thrombocytopenia along with decrease fibrinogen and prolonged prothrombin time as well as low complement rates. She had massive splenomegaly with portal hypertension, and the partial oxygen pressure values in mesenteric and portal blood were concurrent with the presence of arteriovenous shunts. The leucocyte and platelet count, the serum complement, the fibrinogen rate and the prothrombin time recovered after splenectomy. The cavernous characteristics of the spleen, containing multiple thrombi, were confirmed upon scanning electron microscope examination. The pathophysiology of the cytopenias and clotting factors consumption is discussed, stress being laid on the ultrastructural findings. A review is presented of the clinical aspects, differential diagnosis and treatment. PMID- 1621187 TI - [Appearance of different panmyelopathies in the same patient]. PMID- 1621189 TI - [Mortality from childhood and adolescent leukemia in Spain (1951-1985)]. AB - PURPOSE: To study the mortality due to leukaemia during childhood and youth in Spain in the period 1951-1985. MATERIAL AND METHODS: The mortality for all types of leukaemia in that period was studied in three aspects: (a) By reviewing the rates of specific mortality for ages under 20 years, at quinquennial intervals and per millions of inhabitants of those ages. (b) Studying the mortality per cohorts of births at five-year intervals from 1951-1955 to 1981-1985. (c) Attaining the statistical value, "observed deceased" of leukaemia in people under 15 years of age for the period studied and on each year of that period, and comparing such value with the number of "expected deceased", with regard to the reference year, 1965. RESULTS: A decreasing trend was observed along the whole period. As for ages, there seems to be some tendency to stabilisation of the mortality in the last five-year period, 1981-1985 (there is a decrease only in the 15-18 age-group). These data were confirmed when assessing the mortality per "birth cohorts" or generations, and after plotting the figures of "observed" and "expected" mortality in accordance with the previous evolution. CONCLUSION: It was inferred that regard to the mortality of childhood and youth leukaemia, in Spain the situation has improved markedly, doubtless as a result of better therapeutical approach. This evolution closely resembles the patterns of the most developed countries from a sanitary standpoint. PMID- 1621188 TI - [Late recurrence (11 years) in a case of ALL. Recurrence or a second disease?]. PMID- 1621190 TI - [Evaluation of the Coulter STKS hematologic autoanalyzer]. AB - PURPOSE: To express the results of an evaluation of the Coulter STKS blood cell counter. MATERIAL AND METHODS: The following data were collected: inaccuracy, carry-over, linearity, comparison with other systems, suspect morphology alarms, stability of calibration, time-stability of samples and working velocity. The protocol recommended by the ICSH was followed for the first four of the above. RESULTS: Good results were achieved for cell counts and derived parameters. The leucocyte differential count showed fair results for neutrophils, lymphocytes, monocytes and eosinophils; false basophilia was usually associated with the presence of abnormal lymphocytes. No differences were found between adult and paediatric samples. The usefulness of the suspect morphology alarms was also evaluated; they were found fairly sensitive for the presence of stabs, large amounts of atypical lymphocytes and blast cells, and moderately sensitive for erythroblasts and platelet clumps. The predictive value of alarms was found high in any type of pathology, but scarcely valuable when considering the pathology indicated by the alarm, such predictive value being noticeably increased upon associated alarms. CONCLUSION: The Coulter STKS cell counter appears as adequate for the haematology laboratory running daily high number of samples with high pathologic rates. PMID- 1621191 TI - Income, assets, and health insurance: economic resources for meeting acute health care needs of the aged. AB - In this article, the authors use data from the Survey of Income and Program Participation (SIPP) to examine the relationship between economic resources and acute health care needs among the aged. The circumstances of individuals who rely on Medicare as their only form of health insurance are considered in detail because they are potentially more vulnerable when faced with health care expenses. Particular attention is given to the amount of family income and personal contingency assets held by this group and the level of out-of-pocket liability for acute care they might have been expected to face in 1984. The authors point out that their research findings would be strengthened by linkage of a more current SIPP data set to Medicare program records and the development of Medicaid eligibility simulation capability in the SIPP context. PMID- 1621192 TI - The Social Security Administration's 10-percent sample file of OASDI beneficiaries. AB - This is another in a series of technical articles describing Social Security Administration sample files and statistical systems. The focus of this article is the 10-percent sample file that provides program and demographic information on Social Security beneficiaries under the Old-Age, Survivors, and Disability Insurance program. The article explains the contents and availability of the 10 percent sample and presents several statistical tabulations as examples of the wide variety of data that can be developed from the file. PMID- 1621193 TI - The role of prophylactic subtotal colectomy in metachronous carcinoma of the colon and rectum. AB - The risk of metachronous carcinoma of the colon and rectum at 40 year follow-up evaluation is as high as 30 percent. Because of this risk, we reviewed a series of 767 patients treated surgically for carcinoma of the colon and rectum to define a possible prophylactic role for subtotal colectomy. Patients being treated for metachronous carcinoma of the colon and rectum represented 1.6 percent of all patients undergoing surgical treatment for carcinoma of the colon and rectum during this period. There was an early group (less than 2.5 years) and a late group (greater than eight years); with respect to time interval between lesions, the early group possibly representing missed synchronous lesions. Forty six percent of the patients had associated adenomas. Evaluation of the colon with preoperative colonoscopy may eliminate the "early" metachronous lesions that are probably missed synchronous lesions. The presence of adenomas in a younger patient with a primary carcinoma of the colon and rectum represents a high risk of future carcinoma. Subtotal colectomy should be considered in these patients and may also improve the life-long follow-up evaluation required by allowing proctosigmoidoscopy alone to evaluate effectively the remaining colon and rectum. PMID- 1621194 TI - Lower survival rate for patients with carcinoma of the stomach of Borrmann type IV after gastric resection. AB - Between 1965 and 1985, 194 of 1,113 patients (17.4 percent) with advanced carcinoma of the stomach who underwent gastric resection had Borrmann type IV carcinoma of the stomach, a macroscopically evident and diffusely spreading tumor. These patients tended to be younger and female and to have larger tumors that involved the entire stomach, as compared with patients with other types of carcinomas. Tissues were commonly undifferentiated, serosal invasion was prominent with infiltrative growth and high rates of metastasis to the lymph nodes and peritoneal dissemination were evident. In most instances, the disease was advanced; therefore, total gastrectomy was performed upon 82.0 percent of the patients and a palliative resection was done in 64.4 percent. The survival rate was lower than for patients with carcinoma of the stomach of other types (p less than 0.01). A multivariate analysis indicated that curative resection is an independent favorable prognostic event, while other factors are dependent covariates. Early detection of this carcinoma is crucial to extend survival time of patients with Borrmann type IV carcinoma of the stomach. Aggressive postoperative chemotherapy should be considered when a noncurative resection is done. PMID- 1621196 TI - V-Y plasty for perianal reconstruction after resection of tumor. AB - A patient with combination of perianal condylomas and Bowen's disease is described. After resection of the tumor, the defect was repaired by use of V-Y plasty using triangular island skin flaps and split thickness skin grafts. After repair and reconstruction of the perianal area, the patient regained full continence. PMID- 1621195 TI - Surgical approach to segment I for malignant tumors of the liver. AB - Seven complete and 13 partial resections of segment I (caudate lobe) were performed for malignant tumors. In all except one instance, removal of segment I was combined with other types of hepatic resection for technical or carcinologic reasons. Six were iterative hepatic resections for recurrent hepatic metastases. In two, the future remaining left lobe was hypertrophied by right portal venous embolization preoperatively. Hepatectomies were performed with intermittent portal triad clamping (mean total duration of 63 minutes, range of 20 to 120 minutes) and after preparation for total vascular exclusion. Associated partial resection of the inferior vena cava was necessary in three instances. Mean duration of operation was 285 minutes (range of 60 to 540 minutes) and mean blood loss was 1,749 milliliters (range of 200 to 5,200 milliliters). There was no postoperative mortality and the morbidity rate was low. Surprisingly, we discovered retrospectively that free margins were small (less than 5 millimeters) in 83 percent of the patients. Regardless of limited free margins and six iterative hepatectomies, eight patients were free of disease with a mean follow up examination period of 19.2 months. Technical problems were different for each patient and a patient by patient adaptation was necessary. Left, right and central approaches were used accordingly. If resection of segment I associated with a right or left hepatectomy can be currently considered as a standard hepatic resection, isolated complete resection of segment I remains a real technical challenge. PMID- 1621197 TI - The influence of an attachable subcutaneous cuff for preventing triple lumen catheter infections in critically ill surgical and trauma patients. AB - One hundred and ninety-one triple lumen central venous catheters were placed into 107 sites in 81 surgical and trauma patients who were prospectively studied to determine the rate of catheter related infection using a subcutaneous cuff of biodegradable collagen containing bactericidal silver and a guide wire exchange protocol. Thirty-seven sites in 36 nonseptic patients (group 1) were compared with 70 sites in 45 septic patients (group 2). The data were also compared with data consecutively collected one year earlier, using the same exchange protocol without the cuff. Fourteen of 70 sites in group 2 had catheter related infections, with seven causing bloodstream infection. Five of 14 were the result of fungus, with three causing fungemia. Two of 37 sites in group 1 had catheter related infections (p = 0.044), with no associated bacteremia. The number of triple lumen catheter related infections and associated bacteremia or fungemia are higher in septic patients compared with nonseptic critically ill surgical and trauma patients. The cuff significantly prolongs time of catheter site use in patients who are nonseptic, but may be of no benefit in reducing infection rates or prolonging site use time in patients who are septic and may predispose to fungal colonization. PMID- 1621198 TI - A study of cholelithiasis during pregnancy and its relationship with age, parity, menarche, breast-feeding, dysmenorrhea, oral contraception and a maternal history of cholelithiasis. AB - We prospectively studied 512 consecutive women attending the antenatal clinic of the Rotunda Hospital of Dublin, Ireland, to assess the prevalence of gallstones among them and to describe the characteristics of those women found to be gallstone-positive (group 1), compared with the negative-control population (group 2). Real-time ultrasound scanning of the pelvic area was extended to the upper part of the abdomen. Cholelithiasis was detected in 23 patients. No substantial difference was found in parity of group 1 as compared with group 2. Also, early pregnancies, age at menarche and oral contraception did not have any significant difference between the two groups. However, we recorded a significantly higher prevalence of cholelithiasis in older women and in patients with dysmenorrhea. A positive trend was found in patients who had a history of previous breast-feeding and in women with a positive maternal history of symptomatic gallstones. PMID- 1621199 TI - A prospective study on intermittent pneumatic compression in the prevention of deep vein thrombosis in patients undergoing total hip or total knee replacement. AB - Three hundred and forty-six consecutive patients undergoing total hip or total knee replacement were prospectively studied to evaluate the effectiveness of intermittent pneumatic compression of the legs for the prevention of postoperative deep vein thrombosis. All patients were serially studied using impedance plethysmography and duplex ultrasound with color flow preoperatively and on the fourth and seventh postoperative day. The incidence of postoperative deep vein thrombosis in this series was 4 percent. Each patient with a postoperative duplex ultrasound had positive impedance plethysmography. Of the 14 patients who had postoperative deep vein thrombosis, seven had positive test results on postoperative day four and seven had positive tests on postoperative day seven. No patients were symptomatic. The results suggest that the high incidence of postoperative deep vein thrombosis after extensive orthopedic operation is significantly lowered by the use of intermittent pneumatic compression. Intermittent pneumatic compression, therefore, may be the preferred approach in prophylaxis of postoperative deep vein thrombosis. PMID- 1621200 TI - A prospective study of the effect of cholecystectomy on duodenogastric reflux in humans using 24 hour gastric hydrogen monitoring. AB - Duodenogastric reflux (DRG) was quantified with continuous 24 hour monitoring of gastric pH in 30 patients, 12 of whom underwent operation for repair of an inguinal or femoral hernia used as a control group. The remaining 18 patients with noncomplicated gallstone disease underwent a simple cholecystectomy. Eight weeks after the operation, the tests were repeated. We found that patients with cholelithiasis were accompanied with DGR or alkaline shift more often than the patients in the control group and cholecystectomy decreased the percentage of time that gastric pH was less than two and increased the time at four and six. Although cholecystectomy itself does cause DGR, most patients with DGR may be asymptomatic. PMID- 1621201 TI - Short term treatment with leuprolide acetate is a successful adjunct to surgical therapy of leiomyomas of the uterus. AB - Gonadotropin releasing hormone analogs (GnRHa) have been used to induce a reduction in the size of leiomyomas of the uterus after three to six months of therapy. However, none of the studies have noted a significant decrease in size by the first month. Additionally, the results of two reports have suggested long term therapy with GnRHa induced significant aberrations of serum lipoproteins. To evaluate whether or not analog treatment for a short course (two months) would be efficacious, 27 patients with leiomyomas documented by examination of the pelvic area and vaginal ultrasound, who desired to preserve reproductive potential, had myomectomies two and one-half months after commencing depot leuprolide acetate therapy. The reduction in size of the uterus was 35 percent by the first month and the average reduction in the total volume was 44 percent after two months of treatment (474 +/- 364 to 265 +/- 173 milliliters; p less than 0.01). Furthermore, the size of the uterus, determined by examination, decreased significantly from 13.6 +/- 4.0 weeks initially to 10.1 +/- 3.0 weeks preoperatively (p less than 0.0001). Estradiol levels became menopausal by one month of therapy and remained suppressed preoperatively. Menopausal symptoms were well tolerated. Cholesterol, high density lipoprotein, extremely low density lipoprotein and triglyceride levels were not altered by analog treatment, although low density lipoprotein increased from 117 to 130 milligrams per deciliter. A short course of depot leuprolide acetate reduced the size of leiomyomas and surgical tissue planes were preserved, facilitating removal of leiomyomas, and furthermore, there was no significant clinical alteration in lipoprotein or triglyceride levels. PMID- 1621202 TI - Modified highly selective vagotomy. AB - After highly selective vagotomy, the conversion to a positive Hollander test with time is associated with an increased incidence of recurrent duodenal ulceration. In 24 consecutive patients (20 men and four women with an average age at the time of operation of 41 years) with refractory symptomatic duodenal ulceration, a polytetrafluoroethylene patch placed against the esophagogastric parts denervated by highly selective vagotomy completely prevented ulcer recurrence. All of the patients had negative Hollander test results for a five year period. PMID- 1621203 TI - Creation of a pericardial window using thoracoscopic techniques. AB - The aforementioned minimally invasive technique allows the surgeon to create a large pericardial window with minimal morbidity. Adequate long term drainage is provided and sufficient specimen for pathologic examination is obtained. PMID- 1621204 TI - A simple method of preparation of autologous fibrin glue by means of ethanol. AB - We describe herein a new system for the preparation of autologous fibrin glue by means of ethanol. The system produces a good yield of fibrin glue with a high concentration of fibrinogen in a short period of time, making the glue an efficient hemostatic agent and surgical sealant, and autologous fibrin glue has the obvious advantages of safety from transmission of viral agents and from immunologic reactions. PMID- 1621205 TI - Care of the wounded of the United States Army from 1775 to 1991. PMID- 1621207 TI - Appraisal of anti-idiotypic antibodies in the treatment of solid tumors in humans. AB - Anti-idiotypic antibodies may be valuable in the induction of antitumor immunity in two ways--they can serve as a ready source of antigen when the appropriate TAA is difficult or impossible to purify. More importantly, regulatory anti-idiotypic antibodies can activate specific T-helper cells, bringing all the components of cellular immunity to bear on neoplastic process. Although the results in studies in animals have demonstrated resistance to tumor challenge after immunization with anti-idiotypic antibodies, studies of humans with advanced malignancies have failed to produce substantial clinical results. Nevertheless, immunization with anti-idiotypic antibodies has influenced some tumors. These studies represent important, initial steps toward understanding the immune network and modulating it in favor of the host, against human tumors. As a continued understanding of the immune network evolves and strategies for activating and suppressing specific immune responses are developed, it should be possible to design vaccines for specific uses. Although current anti-idiotypic vaccines do not seem promising for the treatment of established solid tumors in humans, we can look with anticipation to studies of polyvalent vaccines for the prevention of carcinoma in high risk groups. PMID- 1621206 TI - Diagnosis of acute diffuse pulmonary infiltrates in immunosuppressed patients by open biopsy of the lung. AB - Herein is a review of the results of open biopsies of the lung performed upon immunosuppressed patients between the years 1982 and 1988. The goal was to assess the safety and value of the procedure on a group of patients who are many times in extremis because of multiorgan failure. Obtaining the correct diagnosis and establishing treatment poses a challenge. The study includes 74 patients. Fifty four had malignant tumors; 20 had various diseases associated with immunosuppression. The biopsy was obtained from the left side in 65 instances. An adequate thoracotomy was done to permit exploration of the thoracic cavity and obtain a representative sample of tissue. The mortality rate related to the operation was 1.4 percent and the complication rate was 11.0 percent. Forty-six percent of the infiltrates were the result of infection. In 42 percent, a change in treatment was made. Thirty-two percent survived and were discharged from the hospital. Patients with adverse drug reaction, with nonspecific pneumonitis and with bacterial infection had a favorable prognosis and benefited most from open biopsy of the lung. PMID- 1621208 TI - International abstracts of surgery. PMID- 1621209 TI - Phase I study of hyperfractionated accelerated radiation and simultaneous Carboplatin therapy for advanced head and neck carcinomas. AB - From 1990 to 1991 15 patients with advanced head and neck carcinomas underwent hyperfractionated accelerated radiotherapy (2 x 1.6 Gy/day, five days/week, total dose 64.0 to 67.2 Gy) and simultaneous intravenous application of Carboplatin (60 mg/m2, days 1 to 5 and 29 to 33) in a pilot study. Eleven patients had T4 and four had T3 tumours. At the end of treatment twelve patients had a complete tumour remission and in the others a partial tumour involution was seen. Although acute side-effects were more pronounced compared to conventional irradiation this treatment regimen is feasible and the initial complete remission rate of 80% is encouraging. PMID- 1621210 TI - Radiation therapy for the esophageal carcinoma: external irradiation versus high dose rate intraluminal irradiation. AB - From September 1977 through December 1989, 149 patients with esophageal carcinoma were treated with external irradiation (EI) with or without high-dose rate intraluminal irradiation (HDRII) using remote afterloading system. Two-year relapse-free survival rates were 52% in sage I (n = 23), 24% in stage II (n = 61) and 19% in stage III (n = 65). Two-year survival rates were 66% in complete response (CR) group (n = 65) and 7 to 9% in non-CR group (n = 84). Concerning CR group external irradiation alone (mean +/- S. D.: 66.5 +/- 5.2 Gy) showed higher local control rate than EI (60.0 +/- 0.4 Gy) + HDRII (10 Gy) (30/38 versus 15/27, p = 0.044), especially in ulcerative type (17/19 versus 5/11, p = 0.009). This preliminary result suggests that HDRII is not effective for the local control of the ulcerative lesion as a boost therapy. PMID- 1621211 TI - Radiotherapy of local recurrence following radical prostatectomy. AB - Between 1977 and 1991, 20 patients with radical prostatectomy for adenocarcinoma of the prostate and palpable, biopsy-proven local recurrence without evidence of metastases underwent radiotherapy. Of these patients 16 were treated with orchiectomy combined with irradiation and four patients underwent irradiation alone. Local control, as determined by rectal palpation was achieved in 19/20 patients. Eleven patients are still alive without disease. Disease-free survival (determined since 1987 including PSA) was 68% for five years and 41% for ten years. 6/9 patients have died with cancer, three patients died intercurrent free of disease. Overall survival remained 51% for five years and 31% for ten years. Prevention of local recurrence is of great importance and these data support the adjuvant post-operative irradiation in defined patients at risk. PMID- 1621212 TI - Subsequent malignancies in patients treated with 131-iodine for thyroid cancer. AB - I-131 was administered to 298 patients with thyroid cancer, and there has been a follow-up of at least two years. Follow-up periods were: 2.5 to 30 years (median 14.5) in living patients, 2.5 to 15 years (median 5.5) in patients dead of tumour greater than or equal to 2 years after first treatment and 2.5 to 23 years (median nine) in patients dead without tumour. Person-years at risk were (total applied activity of I-131): 1119 (3 to 21 GBq), 1477 (22 to 65 GBq), 521 (61 to 170 GBq). 33 subsequent malignancies in 31 patients were observed, compared to an expected number of 17. The relative risk of subsequent malignancies is therefore 1.94 with a 95% confidence interval of 1.15 to 3.05. This increase in the incidence of subsequent malignancies after I-131 treatment is largely due to the significantly increased incidence of leukemia and bladder cancer. Estimated radiation doses to the bone marrow in the patients with leukemia were 301 cGy to 792 cGy and the doses to the bladder in patients with bladder cancer were 2250 cGy to 10, 350 cGy. After a total activity of less than 37 GBq I-131, no cases of bladder cancer or leukemia were observed. The observed number of subsequent malignancies are compared with the expected number according to several dose effect estimations. PMID- 1621213 TI - [Hypertension as risk factor for increased rate of side effects in the framework of breast carcinoma irradiation]. AB - The rate of radiation-induced side-effects is dependent from exogenous technical and endogenous factors. Widespread endogenous factors are arterial hypertension and other cardiovascular diseases. 130 breast cancer patients were retrospectively evaluated for side-effects to estimate the influence of arterial hypertension. All were treated with mastectomy and irradiation (telecobalt) and consecutively followed. 79 patients had normal blood pressure, 51 showed arterial hypertension. Hypertension proved to be the strongest endogenous factor for the development of side-effects. In contrast to the patients with normal blood pressure those with hypertension showed significant more arm lymphedema (p less than 0.005) and telangiectasia (p less than 0.0001). Other endogenous factors, like cardiovascular diseases or obesity, taken together led only to a higher rate of subcutaneous fibrosis (p less than 0.002). Patients with arterial hypertension should receive axillary radiation only for strict indications and perhaps with a reduced dosage. PMID- 1621214 TI - [High-voltage radiotherapy of cavernous giant hemangioma? An impressive case example]. AB - Because of multifonus of therapeutic possibilities in treating cavernous haemangioma, we mostly, but primarily due to frequent spontaneous regression tendency, we exercise restraint. However, if irradiation is taken into consideration, it is mainly with "soft" X-rays (100 kV). The application of high voltage X-rays (1 MeV) by means of linear accelerator is seldom and rarely found in literature. That this method can be effective and indication for this is absolutely in order and life-saving, is described in an impressive case example of a congenital giant haemangioma on the right facial half of an infant, where all other previous forms of therapeutical procedures had failed. PMID- 1621215 TI - [Electron microscopic studies on the effects of irradiation and mitoxantrone hydrochloride (Novantrone), alone and in combination, on cells of Harding-Passey melanoma in monolayer culture]. AB - 2 Gy or 4 Gy irradiation of cultured Harding-Passey melanoma cells revealed electronmicroscopically none or little cell damage. 48 hour exposure of cultures to mitoxantrone concentrations of 1 x 10(-8) M or 3.3 x 10(-8) M also exhibited little cell damage. However, combination of these treatments--in comparison with single treatment--resulted in increased cell damage. The present paper describes the extent of Harding-Passey melanoma cell damage following a radiation exposure (2 or 4 Gy) or a mitoxantrone treatment (1 x 10(-8) M or 3 x 10(-8) M) for 48 hours alone or in combination. PMID- 1621216 TI - Prophylaxis against perioperative cardiac ischemia-reperfusion injury. PMID- 1621217 TI - Gangrenous cholecystitis as a complication of hepatic artery embolization: case report. AB - Ischemic injury to the gallbladder has been described after hepatic artery embolization but has not been considered a clinically significant complication of this procedure. We present three cases in which therapeutic embolization resulted in symptomatic gangrenous cholecystitis requiring urgent surgical intervention. Clinical parameters that distinguish this infrequent ischemic septic process from the more common postembolization syndrome are discussed and recommendations concerning the diagnosis and management of these complicated patients are outlined. PMID- 1621218 TI - Immunosuppression in patients with Barrett's esophagus. AB - BACKGROUND: Patients with Barrett's esophagus have a higher incidence of esophageal cancer than has the general population. Local tissue injury and exposure to carcinogens presumably play a role in malignant transformation, but the possibility of altered host immune surveillance must also be considered. METHODS: The level of immunoreactivity was investigated in six healthy control subjects; 14 patients with gastroesophageal reflux, seven with and seven without esophagitis; and nine patients with Barrett's esophagus. Parameters studied were (1) T-cell and B-cell function with mitogen-stimulated lymphocyte blastogenesis, (2) immunosuppressive properties of autologous serum, and (3) interleukin-2 production by peripheral blood mononuclear cells. Nutritional status as a possible cause for immunosuppression was assessed by measurement of serum albumin, transferrin, and prealbumin. RESULTS: Patients with Barrett's esophagus had a significant suppression of all T-cell (p less than 0.01) and B-cell function (p less than 0.01) and interleukin-2 production (p less than 0.001) when they were compared to the controls. Interleukin-2 production was also reduced significantly compared to that in patients with gastroesophageal reflux with and without esophagitis (p less than 0.05). No differences were observed in serum immunosuppression or nutritional factors. CONCLUSIONS: Although the immunosuppression observed in the patients with Barrett's esophagus was milder than that found in other immunocompromised states, it may be sufficient to encourage the malignant transformation of Barrett's mucosa. PMID- 1621219 TI - Restoration of general surgery in an age of subspecialties: an educational proposal. PMID- 1621220 TI - General surgery--the wellspring of surgery. PMID- 1621221 TI - Immunosuppression in patients with Barrett's esophagus: one piece of the puzzle? PMID- 1621222 TI - Changes in growth factor levels in human wound fluid. AB - BACKGROUND: It has been suggested that platelet-derived growth factor (PDGF) plays a central role in wound healing. Analysis of human wound fluid revealed the presence of PDGF AA (30 kd) and monocyte/macrophage-derived growth factor (MDGF) (12 to 14 kd) in the immediate postoperative period. METHODS: The amount of PDGF AA present was assayed by Western blot analysis. The chemotactic and mitogenic potential of purified wound fluid containing PDGF AA and MDGF was determined on a responsive cell line. The biologic activity of MDGF was assayed with a cell line that is unresponsive to the PDGF AA found in wound fluid. RESULTS: Both the concentration and the biologic activity were highest in the immediate postoperative period and declined to negligible levels by 24 hours after surgery. The chemotactic activity of MDGF was highest in the immediate postoperative period and declined during the first 24 hours in a manner similar to that of the combined PDGF AA and MDGF activity. CONCLUSIONS: These data demonstrate the changing levels of PDGF and MDGF in human wound fluid over time, supporting the cascade model of wound repair. By demonstrating that MDGF acts on cell lines unresponsive to the PDGF AA found in wound fluid, these data suggest that MDGF may also play an important role in wound healing. PMID- 1621224 TI - Xenografts: is there a future? PMID- 1621223 TI - Prophylaxis of infection with intravenous immunoglobulins plus antibiotic for patients at risk for sepsis undergoing surgery for colorectal cancer: results of a randomized, multicenter clinical trial. AB - BACKGROUND: The results of a randomized, multicenter clinical trial with perioperative short-term antibiotic plus intravenous immunoglobulins (IVIG + A) versus antibiotic alone (A) for prevention of postoperative infections in patients at risk for sepsis undergoing surgery for colorectal cancer are presented. METHODS: The patients at risk for sepsis were selected by an original multiparametric test based on delayed-hypersensitivity skin testing and serum protein electrophoretic subfractions. This screening had shown 76% positive predictability in a previous validation assessment. Eighty patients at risk for sepsis were selected prospectively from 210 patients undergoing surgery for colorectal cancer; 43 patients were randomly assigned to the IVIG + A group and 37 to the A group. IVIG was administered on the day before operation, on the first and fifth postoperative days. RESULTS: There was a clear-cut reduction of postoperative infections in the IVIG + A group: 21 infections in 20 patients versus 37 infections in 29 patients in the A group (p less than 0.004). With regard to serum immunoglobulin (Ig) G monitoring, basal IgG levels were significantly lower in patients given IVIG + A who had postsurgical infections (p less than 0.005) compared with patients with a regular outcome, whereas the same was not true in the A group of patients. CONCLUSIONS: A significant decrease (p less than 0.001) of postoperative IgG was evidenced in the A group of patients who had infections as opposed to a significant increase (p less than 0.001) of postoperative IgG in IVIG + A patients with a normal outcome. PMID- 1621226 TI - In situ saphenous vein for lower extremity revascularization. AB - BACKGROUND: During a 6-year period, 349 in situ saphenous vein bypass grafts were performed for limb salvage by three surgeons. METHODS: Outflow anastomoses were constructed to the infrageniculate popliteal (25%), posterior tibial (20%), peroneal (20%), anterior tibial (19%), and dorsal pedal arteries (7%). Mean patient age was 70 1/2 years. RESULTS: The 30-day mortality rate was 3.2%, and 19% died during the ensuing 68-month interval. At 1, 24, and 60 months primary graft patency was 89%, 77%, and 74%, secondary graft patency was 91%, 80%, and 78%, and cumulative limb survival was 94%, 88%, and 84%, respectively. Cumulative patency rates at 60 months depending on outflow site were as follows: popliteal (85%), anterior tibial (80%), posterior tibial (70%), dorsal pedal (68%), and peroneal (60%). Patency at the peroneal position was significantly inferior to that of other infrapopliteal sites combined (p less than 0.05). Cumulative limb survival at 60 months, according to outflow site, was as follows: popliteal (95%), anterior tibial (85%), posterior tibial (78%), dorsal pedal (73%), and peroneal (67%). There was no significant difference in limb salvage among infrapopliteal outflow sites. However, patency rates and limb salvage were significantly better for the popliteal outflow site than the infrapopliteal outflow sites (p less than 0.01). CONCLUSIONS: (1) A 5-year graft patency rate of 78% and a limb salvage rate of 84% are achievable, (2) peroneal bypass is associated with a lower rate for graft patency but not limb salvage, and (3) popliteal bypass has the best graft patency and limb salvage rates. PMID- 1621225 TI - Oxygen kinetics in experimental sepsis. AB - Systemic oxygen delivery (DO2) is normally four to five times higher than oxygen consumption (VO2), and VO2 is independent of DO2. If DO2 is decreased to less than twice VO2, a state of anaerobic metabolism and supply dependency occurs. Some authors have reported that this biphasic relationship is altered in the adult respiratory distress syndrome or sepsis to a condition of continuous supply dependency. If that were true, it would affect both our understanding and management of metabolism during sepsis. Therefore we measured VO2 and DO2 in a dog peritonitis model. DO2 was regulated with controlled pericardial tamponade. During sepsis VO2 increased 28% from a mean baseline of 5.6 to 7.3 cc O2/kg/min (p less than 0.005). As progressive cardiac tamponade was applied during sepsis, the DO2/VO2 ratio fell. When the DO2/VO2 ratio was greater than 2.4, VO2 remained independent of DO2. At DO2/VO2 ratios less than 2.4, VO2 was dependent on the level of DO2, and it diminished rapidly as DO2 decreased. Oxygen saturation in mixed venous blood (SvO2) consistently reflected the DO2/VO2 ratio in a fashion similar to that in normal dogs. A ratio of DO2/VO2 of 2.4 corresponded with an SvO2 of 42% +/- 12%, which was identified as a statistically significant critical SvO2 that marked onset of VO2 supply dependence. In this dog septic model, VO2 is independent of DO2 when DO2 is adequate. A state of continuous supply dependency does not exist. SvO2 reflects the status of the DO2/VO2 relationship in the septic state. PMID- 1621227 TI - Lung injury produced by pancreatic proteases in dogs. AB - With an isolated, blood-perfused canine lung-lobe preparation, the potential role of reactive oxygen metabolites and neutrophils in pancreatic protease (alpha chymotrypsin)-induced acute lung injury was studied. Administration of alpha chymotrypsin caused a low-pressure pulmonary edema (mean lung lobe weight increased from 71 to 197 gm). Pretreatment with superoxide dismutase alone did not attenuate the injury (58 to 166 gm), but when combined with catalase, the injury was significantly ameliorated (64 to 107 gm). However, depletion of circulating leukocytes did not attenuate the injury (69 to 200 gm). These findings suggest that circulatory proteases can cause lung injury by a mechanism that is mediated, at least in part, by toxic oxygen metabolites that are not of neutrophil origin. PMID- 1621228 TI - Comparison of laser-assisted fibrinogen-bonded and sutured canine arteriovenous anastomoses. AB - The effect of laser-assisted fibrinogen bonding (LAFB) on the development of intimal hyperplasia was studied with stress-strain profiles and histologic evaluation of canine arteriovenous fistulas (AVFs). In 19 animals femoral AVFs were created with an 808 nm diode laser after topical application of fibrinogen mixed with indocyanine green dye; in the contralateral limb a sutured AVF was created. The animals were divided into three groups. Group 1 dogs (n = 6) were killed serially up to 4 weeks after surgery to examine the healing of the anastomoses created with LAFB. Group 2 dogs (n = 6) were killed 1 month after surgery, and the fresh specimens were strained axially to produce a stress-strain profile graph. Group 3 dogs (n = 7) were killed 7 months after surgery, and the AVFs were infused with formalin under pressure and histologically prepared to allow comparison of the ratio of maximum to minimum intimal hypertrophy. Fibrinogen used for LAFB was resorbed during the first month after operation without evidence of foreign body reaction or inflammation. Tensile break force was not significantly different in the laser-bonded group (4.6 +/- 2.4 pounds) and the sutured group (4.3 +/- 1.7 pounds). The modulus (tensile break force per square inch), a measure of elasticity, identified the laser-bonded AVF (149 +/- 44 pounds per square inch) to be less rigid than the sutured AVF (203 +/- 35 pounds per square inch) (p less than 0.05). No significant differences in the degree of intimal hyperplasia were noted in any area of the anastomoses. Use of LAFB neither accelerates nor prevents intimal hyperplasia in a canine AVF model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621230 TI - Nasogastric tube "suction-buster holes" release mucosal occlusion despite high suction. AB - Aspiration devices can persistently malfunction if moderate (not just high) suction causes mucosal occlusion of every opening. The standard pattern of uniformly large orifices was modified by supplementing half the nasal tubes with smaller (one tenth of the area) openings. Ten pairs of postoperative patients sipped water while suction applied to their nasal tubes varied from 40 to 300 mm Hg. Unmodified tubes consistently functioned only when applied vacuum was below 60 mm Hg. At 60 mm Hg, 20% (2/10) of tubes malfunctioned, with swallows failing to return on three consecutive attempts even at this gentle level. The failure rate rose with increasing applied suction. All 10 devices evidenced persistent occlusion when the vacuum exceeded 90 mm Hg. Each adverse result was confirmed by continued malfunction when suction was increased by another 10 mm Hg. The brisk flow through large esophageal openings dramatically differs from restricted inflow. Supplementing the standard set of uniform, large-bore aspiration orifices with additional small openings results in unimpeded function over the full range of available hospital vacuum. The additional small openings permitted the turbulent evacuation characteristic of large-bore patency. No device with accessory "suction-buster" orifices malfunctioned at even the highest available suction (300 mm Hg). PMID- 1621229 TI - Brachiocephalic revascularization: a comparison between carotid-subclavian artery bypass and axilloaxillary artery bypass. AB - Sixty-seven patients who underwent carotid-subclavian bypass (CSBP) (28 CSBPs only and eight with carotid endarterectomy) or axilloaxillary artery bypass (n = 31) with polytetrafluoroethylene grafts were followed up for a mean of 69.2 and 71.9 months, respectively. Indications for surgery in the CSBP group included hemispheric transient ischemic attack (TIA)/cerebrovascular accident in five, nonhemispheric TIA in seven, upper extremity ischemia in 15, and combined TIA and arm ischemia in nine patients. In the axilloaxillary artery group, two patients had hemispheric TIA, five had nonhemispheric TIA, 12 had upper extremity ischemia, and 12 had combined TIA and arm ischemia. Graft patency was determined clinically and confirmed by segmental Doppler pressures, duplex ultrasonography, or angiography. The 30-day mortality rate was approximately 3% in both groups. The 30-day complication rate was 3% for the axilloaxillary artery group and 8% for the CSBP group (not statistically significant). Relief of symptoms was achieved in 100% of patients in both groups; however, 20% of the patients in the axilloaxillary artery group had a recurrence of symptoms, in contrast to 5.6% in the CSBP group. The cumulative 10-year primary and secondary patency rates, calculated by life-table analysis, were 66% and 84.6% for the axilloaxillary artery procedures and 93.8% and 93.8% for the CSBP procedures, respectively (statistically significant). Concomitant carotid endarterectomy with CSBP did not influence graft patency. In conclusion, both bypasses have comparable morbidity and mortality rates; however, the CSBP has a statistically significantly better primary patency rate than the axilloaxillary artery bypass. Therefore CSBP should be the procedure of choice and the axilloaxillary artery bypass should be restricted to high-risk patients. PMID- 1621231 TI - Temporomandibular joint dysfunction and systemic joint laxity. AB - The purpose of this thesis was to study an inherited disposition, systemic joint laxity, in patients with temporomandibular joint (TMJ) dysfunction. The importance of systemic joint laxity for TMJ dysfunction compared with other supposed etiological factors, such as bruxism and jaw trauma, was analysed in TMJ patients and in non-patient groups. Collagen distribution and mitral valve function were investigated in hypermobile TMJ patients and normal controls. General joint mobility was assessed in 360 participants. Comparing 74 female craniomandibular dysfunction (CMD) patients with 73 controls of the same sex and age, more hypermobile individuals were found in the patient group. Patients with TMJ dysfunction had significantly more hypermobile joints than other patients at a clinic for CMD patients. A multiple stepwise regression analysis established that hypermobility was a more important factor than bruxing for TMJ dysfunction. Trauma to the head and jaw was significantly correlated to TMJ dysfunction only in non-hypermobile patients. TMJ patients had significantly more musculoskeletal complaints than other CMD patients or controls. A non-patient investigation comprising about 200 adolescents showed the females to be significantly more hypermobile than the males. Another indication of a systemic disposition in hypermobile TMJ patients compared with controls was more insufficient mitral valve function in an echocardiographic investigation of 10 hypermobile TMJ patients and 10 normal controls. Skin biopsy revealed lower values of total collagen and a higher ratio of collagen type III to III + I in TMJ patients than in normal controls. PMID- 1621232 TI - [Drug treatment of cholestatic liver diseases]. AB - After a brief summary of the pathophysiology and natural history of different cholestatic disorders novel forms of treatment are considered. Treatment of different syndromes with ursodeoxycholic acid is considered in some depth. While the substance has clearly proven its efficacy in the symptomatic treatment, its influence on hard parameters such as survival and transplantation requirements remains to be documented. S-adenoylmethionine has shown to be efficaceous in some but not all studies on pruritus of pregnancy. The substance holds promise in other cholestatic disorders as well, but clearly more studies are needed before its therapeutic potential can be appreciated. Finally, nowadays orthotopic liver transplantation should be considered early in patients with progressive cholestatic liver disorders. PMID- 1621233 TI - [Alcoholic hepatitis]. AB - Alcoholic hepatitis presents as an acute hepatitis in an alcoholic. No specific laboratory tests for alcoholic hepatitis exist. Therefore, the diagnosis must be based on the clinical presentation, histology and exclusion of other causes of a similar clinical picture such as viruses and drugs. Patients with elevated bilirubin, encephalopathy and coagulopathy have a poor prognosis. Steroids, infusion of insulin and glucagon, supplementation of amino-acids and other experimental therapies do not appear to be helpful with the exception of steroids which may benefit the sickest patients. Long-term prognosis depends on the extent of cirrhotic changes present after the acute episode and on the drinking habits of the patient. PMID- 1621234 TI - [Imaging procedures and fine needle puncture of focal liver lesions]. AB - Ultrasonography, as screening method of choice, answers questions as to the size of the liver, the structure of the parenchyma, focal lesions and the dilatation of the biliary system. To characterize focal lesions, to stage tumors and for a better topographic localization, computed tomography or magnetic resonance imaging is useful. The differential diagnosis of focal lesions, such as cysts, hemangioma or focal nodular hyperplasia is achieved by the combination of laboratory, imaging and nuclear medicine methods. In other cases, needle-biopsy under sonographic or CT guidance is decisive. PMID- 1621235 TI - [Indications and results of liver resection]. AB - A liver resection should only be performed after complete investigation of a detected hepatic lesion and represents a choice between other possible treatments. This choice is influenced by the natural history of the lesion and its extension, by its precise intrahepatic localization by the general condition and symptoms of the patient, and by the results expected from therapeutic alternatives. The most usual indications for hepatectomies are discussed. PMID- 1621236 TI - [Liver biopsy in suspected alcoholic liver damage]. AB - Alcohol can induce a wide spectrum of histological changes in the liver. Three morphologic patterns of alcoholic liver injury are now generally accepted, i.e. fatty change, alcoholic hepatitis and alcoholic cirrhosis, but a broad array of lesions has been added to this list in recent years. These damage patterns differ considerably in their significance as to indication and diagnostic power of liver biopsies. Liver biopsy is recommended in patients with clinically suspected alcoholic liver disease for diagnostic and prognostic reasons. Moreover, clinicians want to exclude nonalcoholic liver diseases that might otherwise be missed. Alcoholic hepatitis, which is associated with increased morbidity and mortality, has the highest degree of diagnostic specificity in biopsies, because its features are well-defined and are mimicked by a rather small group of other causes. When associated with perivenular and pericellular fibrosis, it may provide prognostic parameters. In contrast, fatty liver, which may be induced by alcohol as well as other etiologies, usually does not need liver biopsy, with some exceptions. It may lead to cholestasis severe enough to mimic obstructive jaundice, or may result in abnormal imaging studies suggesting metastases. Verification of histological findings may be important when these circumstances arise. Cirrhosis is easily verified in biopsies of appropriate quality; however, advanced cirrhosis is a morphologically nonspecific alteration, because cirrhotic tissue patterns converge irrespective of their cause. Liver biopsy may help to identify nonalcoholic liver disease in patients suspected of harboring alcoholic liver disease. In fact, up to 20% of biopsies may show other, potentially treatable disorders, thus extending the indication for liver biopsy in situations of complex clinical and laboratory patterns. PMID- 1621237 TI - [Who are the candidates for liver transplantation?]. AB - Over the past 12 years, new immunosuppressive agents, better knowledge of anesthesiology and postoperative reanimation as well as refinement in surgical technics modified the indications for and results of orthotopic liver transplantation (OLT). At the beginning of the OLT era, liver tumors that could only be removed by total hepatectomy were one of the most frequent indications. Nowadays, this indication is mostly abandoned in view of a high rate of recurrence and poor long-term results. In contrast, the prognosis of fulminant hepatic failure has been dramatically improved by OLT, once efficient organization systems allowed adequate organ supply and emergency transplantation within a few hours. Three main groups of diseases (cholestatic diseases, inborn errors of metabolism and parenchymal diseases) can be treated by OLT with excellent results (actuarial survivals of 80 to 90% have been reported at one and 2 years). Later graft dysfunction is rare except for virus B recurrence. Primary biliary cirrhosis and the group of inborn errors of metabolism are regarded as the optimal indications of OLT in adults and children respectively. Precocious evaluation of patients, before advanced stages of the disease associated with multiple complications, should prevent them from dying on a waiting list and decrease operative as well as early postoperative risks. Not only does OLT provide mere survival (among 5 patients with lethal hepatic disease, 4 are alive at 2 years from OLT), it also provides a regained quality of life with a virtually normal (for the price of a daily medication intake) family, professional and sportive life. Such achievements prompt us today to propose early transplantation to these patients. PMID- 1621238 TI - Type I congenital plasminogen deficiency is not a risk factor for thrombosis. AB - The risk of thrombosis in type I congenital plasminogen (PLG) deficiency has been suggested, but is still not confirmed. We studied 40 members of two unrelated families with this disease, and found that 21 were heterozygotes of type I congenital PLG deficiency. Three of them had thrombosis, but the other 18 had no thrombosis. The percentages of family members with no history of thrombosis up to a given age among subjects with type I congenital PLG deficiency and healthy controls were analyzed by the Kaplan-Meier method. No significant difference between the two groups was observed by the generalized Wilcoxon test (p = 0.23). These results suggest that there is no significant correlation between type I congenital PLG deficiency and thrombosis. PMID- 1621239 TI - A randomised, double-blind, placebo-controlled trial of dermatan sulphate for prevention of deep vein thrombosis in hip fracture. AB - Dermatan sulphate (MF 701) is a natural glycosaminoglycan that catalyses thrombin inhibition by heparin cofactor II. The aim of the study was to evaluate the efficacy and safety of MF 701 for prevention of deep vein thrombosis (DVT) in patients with hip fracture. A randomised, double-blind, placebo-controlled design was used to assess two dose regimens of MF 701 in two consecutive study phases. Treatment was started within 48 h from the trauma and continued for 14 days for non-operated patients or until the 10th postoperative day. Bilateral mandatory venography was used to assess the end-point. Eighty patients were included in the first phase (40 MF 701, 40 placebo). MF 701, 100 mg IM b.i.d., did not reduce incidence of DVT from that on placebo and did not induce any bleeding. In the second phase 126 patients were included, with a randomisation ratio of 2:1 (84 MF 701, 300 mg IM b.i.d., 42 placebo). Bilateral venography was obtained for 110 patients. The incidence of DVT was 64% (23/36) in the placebo group and 38% (28/74) in the MF 701 group (p = 0.01; odds ratio [OR] = 0.34, 95% confidence limits [CL] = 0.15-0.80p; proximal DVTs were 42% (15/36) and 20% (15/74), respectively (p = 0.02; OR = 0.36, CL = 0.15-0.89). No significant differences were found in haemorrhagic complications (2.4% in each group), blood loss from drains, blood transfusions, haemoglobin and haematocrit values. This study is the first demonstration that dermatan sulphate is a clinically effective antithrombotic agent without bleeding effects. It also provides evidence of the biological role of heparin cofactor II. PMID- 1621240 TI - A decrease in plasminogen activator inhibitor-1 activity after successful percutaneous transluminal coronary angioplasty is associated with a significantly reduced risk for coronary restenosis. AB - To determine a possible relation of changes in plasma levels of plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA) to the development of coronary restenosis after successful coronary angioplasty (PTCA), we followed 104 patients with a low grade residual stenosis after PTCA (less than 30%) for a period of 12 months. PAI-1 plasma levels (functional activity) and t PA antigen were determined 1 day before PTCA and 3 days, 3 months and 6 months thereafter. Thirty-four patients (32.69%) developed angiographically proven coronary restenosis (group A) within a time range of 4-48 weeks (median 12.5 weeks) after PTCA while the remaining patients (group B) had neither clinical signs nor angiographic evidence of restenosis after 6 months. No significant differences could be demonstrated in t-PA antigen or PAI-1 activity (plasma levels between the two groups of patients the day before PTCA). During the whole observation period t-PA plasma levels were not significantly different between the two groups; however, PAI-1 plasma levels were significantly higher at 3 months and 6 months after PTCA in patients of group A (p less than 0.005). When the pattern of PAI-1 plasma levels over time (increase or decrease between two consecutive time points of blood collection) was used to discriminate between the two study groups only 3.5-18% of patients with a decrease in PAI-1 developed coronary restenosis within the following observation period in contrast to 25-58% of patients with an increase in PAI-1 plasma levels (p less than 0.05 to p less than 0.0005). PMID- 1621241 TI - The predictive value of the hemostasis parameters in the development of preeclampsia. AB - In order to find out which hemostasis parameters would have the predictive value for the development of preeclampsia, modified antithrombin III (ATM, representative of the antithrombin III-serine esterase complex), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), beta thromboglobulin (BTG), antithrombin III (AT III), fibrinogen, fibrin(ogen) degradation product (FDP), FDP D-dimer and euglobulin lysis time (ELT) were measured in 20 normal non-pregnant women, 21 normal pregnant women, 6 high-risk pregnant women, 14 preeclampsia pregnant women, and 5 patients with disseminated intravascular coagulation (DIC). Only tPA and AT III were found significantly different between the preeclampsia and the normal or high-risk pregnant women: tPA was found progressively and significantly increased from the normal pregnant, to the high-risk pregnant, then to the preeclampsia women (p less than 0.05). AT III was significantly lower in the preeclampsia than in the normal pregnant (p = 0.0001) or in the high-risk pregnant women (p = 0.002). In the 2nd trimester, tPA, PAI, fibrinogen and FDP were significantly higher, and AT III was significantly lower in the preeclampsia than in the normal pregnant women, whereas in the 3rd trimester, tPA and AT III were significantly higher or lower, respectively, in the preeclampsia than in the normal pregnant women. No significant difference of ATM could be found between the preeclampsia and the normal or high-risk pregnant women. From the present study, we suggest that tPA and AT III would be used as the main predictors, and FDP and D-dimer as the complementary predictors for the development of preeclampsia and should be detected in the normal or high-risk pregnant women. PMID- 1621242 TI - Functional characterization of a variant factor XII (F XII Locarno) in a cross reacting material positive F XII deficient plasma. AB - The plasma of a healthy woman was found to contain half normal factor XII (FXII) antigen level (0.46 U/ml) without any FXII clotting activity (less than 0.01 U/ml). The variant FXII in this plasma, denoted as FXII Locarno, was partially characterized by immunological and functional studies on the proposita's plasma. FXII Locarno is a single chain molecule with the same size (Mr = 80 kDa) as normal FXII. Isoelectric focusing suggested an excess of negative charge in the variant FXII as compared to normal FXII. In contrast to FXII in normal plasma, FXII Locarno was not proteolytically cleaved upon prolonged incubation of proposita's plasma with dextran sulfate. Adsorption to kaolin was similar for both, abnormal and normal FXII. Incubation of the proposita's plasma with dextran sulfate and exogenous plasma kallikrein showed normal cleavage of FXII Locarno outside of the tentative disulfide loop Cys340-Cys467, but only partial cleavage within this disulfide loop. Furthermore, plasma kallikrein-cleaved abnormal FXII showed neither amidolytic activity nor proteolytic activity against factor XI and plasma prekallikrein. These results suggest a structural alteration of FXII Locarno, affecting the plasma kallikrein cleavage site Arg353-Val354 and thus formation of activated FXII (alpha-FXIIa). PMID- 1621243 TI - Determinants of induction of increased synthesis of plasminogen activator inhibitor type-1 in human endothelial cells by t-PA. AB - Tissue-type plasminogen activator (t-PA) induces synthesis of a rapidly acting inhibitor, plasminogen activator inhibitor type-1 (PAI-1) in human umbilical vein endothelial cells (HUVEC) in culture. In vivo, an analogous process may induce negative feedback on the fibrinolytic system. To define specific determinants in the t-PA molecule contributing to the induction, PAI-1 synthesis was characterized in 35S-methionine labeled HUVEC in response to several molecular variants of t-PA. Catalytically active variants devoid of several specific structural domains in the A-chain retained the capacity to form complexes with PAI-1 and to induce increased concentrations of total PAI-1 (free and complexed) in conditioned media without depleting PAI-1 from the extracellular matrix. Surprisingly, a mutant t-PA with markedly reduced catalytic activity reflecting replacement of the active site serine with threonine (S478T) formed complexes with PAI-1 and induced increased PAI-1 synthesis as well. However, in contrast to wild-type t-PA and A-chain variants, it did not release 35S-methionine labeled PAI-1 from the extracellular matrix. Thus, its effects appeared to reflect increased secretion exclusively. Our results suggest that induction of PAI-1 synthesis in HUVEC by t-PA depends on its protease domain but that an active site serine is not a requirement. PMID- 1621244 TI - Biochemical and biological properties of a recombinant tissue-type plasminogen activator derived from the rat JMI-229 cell line. AB - Recombinant tissue-type plasminogen activator (rt-PA), produced by expression of the genomic t-PA DNA from the JMI-229 cell line, which is of rat origin, in the host cell line, was purified to homogeneity. JMI-229 rt-PA was obtained essentially as a single chain molecule which was quantitatively converted to a two-chain moiety by treatment with plasmin. The plasminogen activating potential of single chain JMI-229 rt-PA was 5-fold lower than that of commercially available human rt-PA (Actilyse) in the absence of fibrin, but comparable in the presence of fibrin; it showed a concentration-dependent binding to fibrin, with a significantly more pronounced binding than Actilyse at low fibrin concentration (85 +/- 8% versus 20 +/- 7% at 0.025 mg/ml fibrin; p = 0.004). In human plasma in the absence of fibrin, the concentrations of both single chain and two-chain JMI 229 rt-PA required to induce 50% fibrinogen degradation in 2 h, were about 15 fold higher than those of Actilyse. Both single chain and two-chain forms of JMI 229 rt-PA and of Actilyse induced a similar time- and concentration-dependent lysis of a 125I-fibrin-labeled plasma clot immersed in human plasma, in the absence of significant systemic fibrinolytic activation. Equally effective concentrations (causing 50% clot lysis in 2 h) were 0.11 or 0.10 micrograms/ml for single chain or two-chain JMI-229 rt-PA, as compared to 0.11 or 0.15 micrograms/ml for single chain or two-chain Actilyse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621245 TI - Human platelets contain scinderin, a Ca(2+)-dependent actin filament-severing protein. AB - A large body of biochemical and morphological evidence suggests that actin polymerizes in response to various stimuli which activate platelets. Previous work has shown the presence in platelets of gelsolin, a Ca(2+)-dependent regulator of actin filament length. This present work demonstrates that human platelets contain scinderin, another Ca(2+)-dependent actin filament-severing protein recently discovered in our laboratory. Extracts prepared from platelets were subjected to DNase-I-Sepharose 4B affinity chromatography. EGTA eluates from the affinity columns contained scinderin as demonstrated by mono and two dimensional polyacrylamide gel electrophoresis and immunoblotting with scinderin antibodies. The concentration of scinderin in platelets was 75 fmol/mg total protein. This might represent 11% of the total actin filament-severing activity if both proteins are equally potent, on a molar basis, in severing actin filaments. Double staining immunocytochemical studies with antibodies against scinderin and rhodamine phalloidin, a probe for F-actin, also demonstrated the presence of scinderin in platelets. These findings suggest that scinderin may participate in the regulation of platelet actin networks. PMID- 1621246 TI - Binding of human platelet glycoprotein Ib and actin to fragments of actin-binding protein. AB - Actin-binding protein (ABP) is degraded into fragments of 190 and 90 kDa by calpain. A monoclonal antibody (MAb TI10) against the 90 kDa fragment of ABP coprecipitated with the glycoprotein Ib (GP Ib) peak observed on crossed immunoelectrophoresis of Triton X-100 extracts of platelets prepared without calpain inhibitors. MAb PM6/317 against the 190 kDa fragment was not coprecipitated with the GP Ib peak under such conditions. The 90 kDa fragment was adsorbed on protein A agarose from extracts that had been preincubated with antibodies to GP Ib. This supports the idea that the GP Ib-ABP interaction resides in the 90 kDa region of ABP. GP Ib was sedimented with the Triton insoluble actin filaments in trace amounts only, and only after high speed centrifugation (100,000 x g, 3 h). Both the 190 kDa and the 90 kDa fragments of ABP were sedimented with the Triton-insoluble actin filaments. PMID- 1621247 TI - The d-enantiomer form of indobufen totally accounts for the anti-cyclooxygenase and antiplatelet activity ex vivo and for the increase in bleeding time by indobufen in man. AB - Indobufen is an antiplatelet drug able to inhibit thromboxane production and cyclooxygenase-dependent platelet aggregation by a reversible inhibition of cyclooxygenase. Indobufen exists in two enantiomeric forms, of which only d indobufen is active in vitro in inhibiting cyclooxygenase. In order to verify that also inhibition of platelet function is totally accounted for by d indobufen, ten patients with proven coronary artery disease (8 male, 2 female, age, mean +/- S.D., 58.7 +/- 7.5 years) were given, in random sequence, both 100 mg d-indobufen and 200 mg dl-indobufen as single administrations in a double blind crossover design study with a washout period between treatments of 72 h. In all patients thromboxane (TX) B2 generation after spontaneous clotting (at 0, 1, 2, 4, 6, 8, 12, 24 h), drug plasma levels (at the same times), platelet aggregation in response to ADP, adrenaline, arachidonic acid, collagen, PAF, and bleeding time (at 0, 2, 12 h) were evaluated after each treatment. Both treatments determined peak inhibition of TXB2 production at 2 h from administration, with no statistical difference between the two treatments (97 +/- 3% for both treatments). At 12 h inhibition was 87 +/- 6% for d-indobufen and 88 +/- 6% for dl-indobufen (p = NS). Inhibition of TXB2 production correlated significantly with plasma levels of the drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621248 TI - Normalization of the haemostatic plugs of dogs with haemophilia A (factor VIII deficiency) following the infusion of a combination of factor Xa and phosphatidylcholine/phosphatidylserine vesicles. AB - The bolus intravenous infusion of factor Xa in combination with phosphatidylcholine/phosphatidylserine (PCPS) vesicles, at a dose of 2.6 x 10( 11) moles and 4.0 x 10(-8) moles/kg body weight respectively, has previously been shown to correct the bleeding diathesis of haemophilic (factor VIII deficient) dogs (Br J Haematol 1988; 69: 491-7). The cuticle bleeding time (CBT) was used as the test to evaluate objectively this response. Transmission electron microscopy was performed to document the evolution of haemostatic plugs forming in the vascular bed of the injured cuticles of both normal and factor VIII deficient dogs with and without treatment with factor Xa/PCPS. The dosage previously shown to normalize the CBT in haemophilic and significantly shorten it in normal animals was used. Subjective and objective observations, using morphometric techniques, were made over a period of 25 min following injury induction. The administration of factor Xa/PCPS was associated with complete and sustained normalization of haemostatic plug development in the haemophiliacs including platelet recruitment, activation and compaction and subsequently fibrinous transformation. In the case of the normals, platelet activation, etc, was exaggerated and fibrinous transformation appeared to be accelerated. The haemostatic plugs forming in the treated haemophiliacs were indistinguishable from those forming in the normals and significantly different, with regard to all parameters measured, from the morphological appearances noted in the untreated haemophiliacs. These data suggest that the correction of the haemostatic defect previously observed results from the normalization of haemostatic plug formation and that this is sustained despite the promotion of systemic fibrinolysis that is also known to occur. PMID- 1621249 TI - Alternative splicing is responsible for the presence of two tissue factor mRNA species in LPS stimulated human monocytes. AB - Although normally absent from the surface of all circulating cell types, tissue factor (TF) can be induced to appear on circulating monocytes by stimulants like bacterial lipopolysaccharide (LPS) and phorbolesters. Northern analysis of RNA isolated from LPS stimulated human monocytes demonstrates the presence of 2.2 kb and 3.1 kb TF mRNA species. The 2.2 kb message codes for the TF protein. As demonstrated by Northern blot analysis with a variety of TF gene probes, the 3.1 kb message arises from an alternative splicing process which fails to remove 955 bp from intron 1. Because of a stop codon in intron 1 no TF protein is produced from the 3.1 kb transcript. This larger transcript should therefore not be taken into account when comparing TF gene transcription and TF protein levels. PMID- 1621250 TI - The poor reliability of factor X chromogenic assays in coumarin treated patients. PMID- 1621251 TI - Subcutaneous heparin therapy during pregnancy: a need for concern at the time of delivery. PMID- 1621252 TI - Extensive venous thrombosis in a case of Behcet's disease associated with heterozygous protein C deficiency. PMID- 1621253 TI - Increase in fibrinolytic activity after erythropoietin therapy. PMID- 1621254 TI - Peri-operative replacement therapy with factor VII concentrate in a patient with severe factor VII deficiency. PMID- 1621255 TI - Metabolism of estradiol and estrone in organ cultures of dorsolateral and ventral prostate of untreated and sex hormone-implanted rats. AB - Since dorsolateral but not ventral prostate undergoes estrogen-induced dysplasia in the androgen-supported Noble rat in 16 weeks, we studied estrogen metabolism by these tissues from untreated and sex hormone-implanted animals. We incubated 8.5 nM [6,7-3H]-labeled estradiol (E2) and estrone (E1) for 21 hours in serum free, prostate-lobe cultures and 8.5 nM [2-3H]E2 with explants from untreated rats and animals treated with testosterone, 5 alpha-dihydrotestosterone, or E2 plus testosterone. Untreated rat ventral prostate metabolized 3.7 times as much E2 to E1 as dorsolateral prostate, whereas the latter tissue converted 2.5 times as much E1 to E2 as the former. After dorsolateral prostate culture with 8.5 nM [6,7-3H]-labeled E2 or E1, 0.6 M KCl-extracted, Sephadex G25-excluded nuclear protein bound preponderantly E2, whereas the counterpart nuclear protein fraction from ventral prostate explants incubated with E2 bound substrate and E1 almost equally. The combination sex hormone treatment decreased E2 metabolism and increased its uptake by the dysplastic dorsolateral prostate. Implantation of 5 alpha-dihydrotestosterone, but not of testosterone, also decreased E2 metabolism to E1 by dorsolateral prostate cultures. Treatments with E2 plus testosterone and with 5 alpha-dihydrotestosterone changed E2 uptake/E1 retention in dorsolateral prostate explants from 2.4 to 7.4 and 8.5, respectively. C-2 tritium release marking the 2,3-catechol estrogen pathway was greater for ventral than dorsolateral prostate, but was unaffected by the sex hormone treatments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621257 TI - Three new D-ring unsaturated sterols from the Mediterranean sponge Topsentia aurantiaca: structure determination and complete nuclear magnetic resonance assignment. AB - Three novel sterols with a rare D-ring unsaturation were isolated from the marine sponge Topsentia aurantiaca and identified as 5 alpha-cholest-14-ene-3 beta,16 alpha-diol (2), 24R-ethyl-5 alpha-cholest-14-ene-3 beta,16 alpha-diol (3), and 24S-ethyl-5 alpha-cholest-14-ene-3 beta,16 alpha-diol (4). The sponge also elaborates a further D-ring unsaturated sterol, 5 alpha-cholest-15-en-3 beta-ol (1), which has been previously described only as a synthetic product. All the 1H and 13C nuclear magnetic resonances of compounds 1 and 2 were assigned to the relevant protons and carbons by bidimensional COSY, HETCOR, and HMQC nuclear magnetic resonance experiments. PMID- 1621256 TI - Effects of a phytoestrogen diet on estrogen-dependent reproductive processes in immature female rats. AB - The study reported here examined the effects of a phytoestrogen diet on progestin receptor induction, vaginal opening, and the onset and maintenance of vaginal cycles in developing female rats. A natural dietary concentration (0.01%) of the isoflavonoid coumestrol was incorporated into the AIN semipurified diet and fed from 21 to 24 days (acute treatment) or from 22 to 60 days (chronic treatment). Progestin receptor induction was observed in the uterus, pituitary, and hypothalamus-preoptic area following acute treatment. Responses were more marked in the uterus and pituitary than in the hypothalamus-preoptic area. Vaginal opening was accelerated by 4 days during chronic coumestrol treatment and occurred at a lighter body weight. Vaginal cycles began on vaginal opening and did not differ in regularity from those of control animals. However, irregular cycles were observed in coumestrol-treated animals at 116 to 131 days, suggesting that chronic coumestrol treatment may have induced some permanent changes in reproductive function. These findings demonstrate that plant estrogens, at natural dietary levels, produce significant, agonistic actions in several estrogen-dependent tissues and processes. PMID- 1621258 TI - Studies of the synthesis of biomarkers. X. Synthesis of 13,17-secodiacholestanes. AB - 13,17-Secodiacholestanes (6) were synthesized from cholesterol (1) in six steps. The key intermediates, (20R)- and (20S)-diacholest-13(17)-enes (3a and 3b), underwent ozonization and reduction to provide (20R)- and (20S)-13,17 secodiacholesta-13,17-dione (5a and 5b), respectively. On Clemmensen reduction, the diones (5a and 5b) yielded the target molecule 6. The structure of an unknown biomarker was shown to be different from the proposed 6 by gas chromatographic/mass spectrometric comparison. PMID- 1621259 TI - Racial/ethnic variations in male testosterone levels: a probable contributor to group differences in health. AB - Racial and ethnic variations in serum testosterone levels were investigated among a large sample of male Vietnam era veterans. Based on geometric means, significant average differences were found between 3,654 non-Hispanic white and 525 black individuals. The geometric mean for testosterone levels among 200 Hispanic individuals was similar to that of non-Hispanic white individuals. Regarding two other racial/ethnic groups (Asian/Pacific Islanders and Native Americans), no significant differences were found, due perhaps to small sample sizes. Results were interpreted as having considerable potential for explaining some of the race differences in the incidences of cardiovascular diseases, hypertension, and prostate cancer. PMID- 1621260 TI - Adrenal steroidogenesis in the guinea pig: effects of androgens. AB - In humans, the onset of adrenache has been found to occur with the appearance of the zona reticularis, the inner zone of the adrenal cortex. Since an increase in the volume of adrenal cortex during maturation in the guinea pig has been associated with the growth of the zona reticularis, we were interested in investigating the changes in adrenal steroidogenesis during maturation in this species. In addition, the effect of androgens on adrenal steroidogenesis was studied. We demonstrated that between 1 and 10 weeks of age, a period of maximal growth of the adrenals in the guinea pig, there is a decrease in the concentrations of adrenal pregnenolone, cortisol, dehydroepiandrosterone, testosterone, androstenedione, and 11 beta-hydroxyandrostenedione, suggesting lower steroid production by the guinea pig adrenals. In plasma, we observed that the concentration of 11 beta-hydroxyandrostenedione (the sole C19 steroid present after castration) remained unchanged during maturation, while cortisol and corticosterone were lower between 1 and 4 weeks of age. Although castration as well as the administration of the antiandrogen flutamide had no effect on adrenal steroidogenesis, dihydrotestosterone caused an inhibition of cortisol and corticosterone levels in the adrenals while the concentrations of progestins (namely, pregnenolone, 17-hydroxypregnenolone, progesterone, and 17 hydroxyprogesterone) tended to increase in the adrenals, thus suggesting that dihydrotestosterone induces a blockade in the steroidogenic pathway.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621261 TI - Production of a monoclonal antibody to cortisol: application to a direct enzyme linked immunosorbent assay of plasma. AB - Cortisol mouse monoclonal antibodies were produced and characterized. Of the four clones studied, supernatant from one clone (A2), compared with other cortisol monoclonal antibodies, showed minimal cross-reactivity to other C21 steroids and was suitable for the direct determination of cortisol in plasma by enzyme-linked immunosorbent assay using a standard 96-well microtiter plate. The enzyme-linked immunosorbent assay uses the immobilized antigen approach, in which cortisol in plasma samples or standards competes with immobilized steroid for antibody binding sites. After washing, the cortisol antibody bound to the wells of the microtiter plate is detected with antimouse immunoglobulin conjugated to horseradish peroxidase. Following further washing, o-phenylenediamine substrate is added. The enzyme-linked immunosorbent assay is robust and semiautomated. The mean +/- SD recovery from plasma was 97% +/- 6%. Precision studies on three different plasma pools showed mean coefficients of variation of 7.6% and 8.6% for within- and between-assay variation, respectively. The satisfactory performance criteria allow its use in the routine laboratory. PMID- 1621262 TI - Subnormal serum testosterone levels in male internal medicine residents. AB - The consequences of sleep deprivation and stress in residency training have not been quantified. In the course of assembling a control group for other studies, we unexpectedly observed a significant (P less than 0.005) and marked depression of serum testosterone levels in healthy male internal medicine residents (means = 11.8 +/- 1.1 nmol/L, n = 7) compared with other hospital personnel (means = 20.6 +/- 5.3 nmol/L, n = 18). Testosterone concentrations in the two groups were entirely nonoverlapping, while luteinizing hormone levels were not significantly different. We conclude that the stress of residency training leads to a quantifiable depression of gonadal function, and that gonadal steroid concentrations may be useful in evaluating measures intended to reduce that stress. PMID- 1621263 TI - Adrenocorticosteroid excretion in salt-sensitive and salt-resistant spontaneously hypertensive rats. AB - Two strains of spontaneously hypertensive rats (SHRs) differ in their susceptibility to the hypertensive effects of dietary NaCl. One strain exhibits a significant elevation of blood pressure after dietary NaCl loading (SHR-S), whereas the other does not (SHR-R). Since differences in adrenocortical steroid production may contribute to NaCl sensitivity, we compared 19 nordeoxycorticosterone (DOC), 18-OH-DOC, aldosterone, and corticosterone excretion in 6-week-old male rats from the SHR-S (n = 24) and SHR-R (n = 24) strains. The rats were housed in metabolic cages (two rats per cage) and given either basal (1%) or high (8%) NaCl diet. Urinary steroids were analyzed using thin-layer chromatography and radioimmunoassay methods. The high NaCl diet elevated the urinary excretion of the four corticosteroids in both rat strains. 19-nor-DOC decreased with time in both the SHR-S and SHR-R strains, and was not different between strains on either diet. Aldosterone was increased in the SHR-S strain compared with the SHR-R strain on the low NaCl diet, but aldosterone was not different between the two strains on the high NaCl diet. Corticosterone and 18-OH-DOC did not differ between strains. These data confirm that 19-nor-DOC is higher in young prehypertensive SHRs and decreases with age. Aldosterone excretion is higher in the SHR-S strain compared with the SHR-R strain on the low NaCl diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621264 TI - Synthesis of 3 alpha,6 beta,7 alpha,12 beta- and 3 alpha,6 beta,7 beta,12 beta tetrahydroxy-5 beta-cholanoic acids. AB - Chemical synthesis of 3 alpha,6 beta,7 alpha,12 beta- and 3 alpha,6 beta,7 beta,12 beta-tetrahydroxy-5 beta-cholan-24-oic acids is described. 3 alpha,12 beta-Dihydroxy-5 beta-chol-6-en-24-oic acid used as the starting material in the synthesis was prepared via oxidation of 3 alpha,12 alpha-dihydroxy-5 beta-chol-6 en-24-oic acid 3-hemisuccinate at C-12 followed by reduction with potassium/tertiary amyl alcohol. alpha-Epoxidation of the ester diacetate of 3 alpha,12 beta-dihydroxy-5 beta-chol-6-en-24-oic acid with m-chloroperbenzoic acid followed by cleavage of the epoxide with acetic acid and alkaline hydrolysis yielded 3 alpha,6 beta,7 alpha,12 beta-tetrahydroxy-5 beta-cholan-24-oic acid (overall yield 25%). N-Methylmorpholine-N-oxide-catalyzed osmium tetroxide oxidation of the ester diacetate of 3 alpha,12 beta-dihydroxy-5 beta-chol-6-en-24 oic acid followed by alkaline hydrolysis yielded 3 alpha,6 beta,7 beta,12 beta tetrahydroxy-5 beta-cholan-24-oic acid (overall yield 33%). The structures of the synthesized bile acids were confirmed from their proto nuclear magnetic resonance and mass spectral fragmentation patterns. PMID- 1621265 TI - Influence of different combinations of antibodies and penicillinase-labeled testosterone derivatives on sensitivity and specificity of immunoassays. AB - Three antisera raised against bovine serum albumin (BSA) conjugates of testosterone-3-(O-carboxy-methyl)-oxime (T-3-CMO), 11 beta-hydroxytestosterone-11 carboxymethyl ether (T-11 beta-O-CME) and 19-hydroxytestosterone-19-carboxymethyl ether (T-19-O-CME) were evaluated in enzyme immunoassays (EIAs) in combinations with penicillinase-labeled T-3-CMO, T-11 beta-O-CME, T-19-O-CME, and testosterone 17 beta-hemisuccinate (T-17 beta-HS) for their influence on the sensitivity and specificity of EIAs. Of the various combinations, anti-T-3-CMO antiserum along with T-11 beta-O-CME-penicillinase showed no cross-reaction with any of the closely related steroids, although the same antibody had 21.6% binding to 5 alpha dihydrotestosterone (5 alpha-DHT) in radioimmunoassay. All the homologous combinations appeared to be less sensitive due to their low affinity for testosterone. It was also apparent that of all the heterologous systems tested, only two combinations, (a) anti-T-19-O-CME antiserum and T-3-CMO-penicillinase and (b) anti-T-3-CMO antiserum and T-11 beta-O-CME-penicillinase, were found to be more sensitive. The former was less specific; it showed 70% cross-reaction with 5 alpha-DHT. The ability of testosterone to displace the hapten-enzyme conjugate and the specificity of the assay appear to depend on the position of the enzyme label on the steroid molecule as well as on the availability of antigenic sites in particular combinations of antibody and hapten-enzyme conjugates. PMID- 1621266 TI - 4,4-Dimethyl-5 alpha-ergosta-8,24(28)-dien-3 beta-ol from the fungus Marasmius oreades. AB - From the fruit body of the fungus Marasmius oreades (family Tricholomataceae), 4,4-dimethyl-5 alpha-ergosta-8,24(28)-dien-3 beta-ol (1), probably a biogenetic precursor of ergosterol, has been isolated along with ergosterol. Its stereostructure has been established unequivocally by spectroscopic methods, including 13C nuclear magnetic resonance. PMID- 1621267 TI - Synthesis and characterization by 1H and 13C nuclear magnetic resonance spectroscopy of 17 alpha-hexanoic derivatives of 5 alpha-dihydrotestosterone and testosterone. AB - The synthesis and characterization of 17 alpha-(6'-hexanoic acid) derivatives of 5 alpha-dihydrotestosterone and testosterone, useful as ligands for affinity chromatography purification or as precursors for affinity-labeling of androgen binding proteins, is described. Alkynylation of 3-ethylenedioxy-, 3 beta-hydroxy , and 3 beta,5-dihydroxy-5 alpha-androstan-17-one precursors with the potassium derivative of 5-hexyn-1-ol led to the corresponding 17 alpha-(6'-hydroxyhex-1' ynyl) derivatives, which were hydrogenated over 10% Pt-C catalyst to give 17 alpha-(6'-hydroxyhexyl) derivatives. Chromic acid oxidation of the primary hydroxy group of the 3-ethylenedioxy-17-hexyl intermediate into carboxylic acid followed by acid cleavage of the 3-ketal group gave 17 alpha-(5'-carboxypentyl)-5 alpha-dihydrotestosterone, which was also obtained directly by chromic acid oxidation of the 3 beta-hydroxy intermediate. Chromic acid oxidation of the primary hydroxy group of the 3 beta,5 alpha-dihydroxy precursor resulted in a 5 alpha-hydroxy-3-oxo intermediate, which was dehydrated to give 17 alpha-(5' carboxypentyl)testosterone. The 17 alpha configuration of these derivatives and of synthetic precursors was established by comparing their molecular rotations and their 1H and 13C nuclear magnetic resonance (NMR) spectra including solvent effects, with data reported for 17 alpha- or 17 beta-substituted steroid analogs as well as with 1H and 13C NMR reference data recorded in this work for 17 alpha ethynyltestosterone, 17 alpha-ethynyl-19-nortestosterone, 17 alpha-ethyl-19 nortestosterone, 17 alpha-methyltestosterone, and 17 alpha-methyl-5 alpha dihydrotestosterone. PMID- 1621268 TI - Synthesis of 25-hydroxy-[6,19,19'-2H3]vitamin D3 and 1 alpha,25-dihydroxy [6,19,19'-2H3]vitamin D3. AB - Synthesis of polydeuterated analogs of 25-hydroxyvitamin D3 and 1 alpha,25 dihydroxy vitamin D3 are described. These analogs, containing stable isotope atoms at metabolically stable positions, are potentially useful in studies involving catabolism of hydroxylated metabolites of vitamin D3. PMID- 1621269 TI - Effects of a normal, human-concentration, phytoestrogen diet on rat uterine growth. AB - The estrogenic action of the prototype natural phytoestrogen coumestrol was examined in rats in in vitro and in vivo tests. To establish the binding specificity of coumestrol and its relation to biological activities, saturation analyses and uterine weight assays were performed. These assays indicated that coumestrol competitively inhibited binding to the estrogen receptor and induced increases in uterine weight in keeping with its estrogen receptor affinity constant. Most importantly, coumestrol was uterotrophic when incorporated in a semipurified diet at natural dietary concentrations. Significant increases occurred in both uterine wet weight and dry weight, indicating that coumestrol produces true uterine growth. Effects appeared to be cumulative, raising questions of time-related interactions with other estrogen-sensitive mechanisms and clearance of isoflavonoids. Coumestrol induced uterine growth over a 90-hour period at dietary concentrations of 0.01 to 0.1%. Lower doses not active over this period were active when provided over a longer period of time: a 0.005% concentration was not active over a 90-hour period, but was active when provided over a 180-hour period. Coumestrol-induced uterine growth was accompanied by the induction of cytosolic progestin receptors and increases in nuclear estrogen binding. Scatchard analyses verified that these changes were due to changes in receptor number. These studies show that the naturally occurring phytoestrogens have dramatic estrogenic effects at natural dietary levels. These actions may be expressed via traditional receptor-mediated actions and therefore may have the same implications for development, health, and disease as do the steroidal estrogens produced by the body. Because rats have no sex hormone-binding globulin, further studies must be conducted in humans. However, these findings suggest that the natural dietary phytoestrogen coumestrol is a potent estrogen that must be considered in calculating the total estrogenic load to which humans are exposed during normal life. PMID- 1621270 TI - Rollerball endometrial ablation: new treatment options for women. AB - 1. Endometrial ablation with a rollerball electrode is an alternative to hysterectomy for selected women with menorrhagia. Patients are usually discharged the same day and recover more quickly than women who undergo hysterectomy. 2. Preoperative patient preparation includes endometrial suppression through drug therapy and placement of a laminaria tent in the uterine cervix. 3. Because large amounts of irrigating solution are used during the procedure, careful monitoring of fluid balance is essential to avoid fluid overload. 4. Diagnostic hysteroscopy is useful for evaluating abnormal bleeding. PMID- 1621271 TI - Personal protective equipment in aseptic technique and universal precautions. AB - 1. Although some of the basic principles of aseptic technique are fundamentally similar, their roles in terms of protection is reversed. 2. Whereas the use of the surgical mask has often been abused, ie, being saved by hanging around the neck, there is reason to believe that masks may only be necessary in those instances where the wearer is exposed to splashes, spray, or spatter of infectious materials. 3. Materials that are liquid-resistant may possess various degrees of resistance. On the other hand, the performance of a material that is liquid-proof is absolute--it is impenetrable and can be accurately described as impervious. PMID- 1621272 TI - Variable segmental plating for the treatment of spinal instability. AB - 1. Posterior lumbar interbody fusion (PLIF) incorporates variable screw placement and slotted plates with transpedicular screws to correct spondylolisthesis, a subluxation or displacement of the vertebrae. 2. The indications for PLIF include degenerative disc disease, recurrent disc herniation, spinal stenosis including the central and lateral foraminal varieties, various forms of instability associated with these disorders, and cases of asymptomatic spondylolysis with or without spondylolisthesis. 3. Complications include infection, fracture of the pedicle, nerve root impingement associated with the bone graft, and screw breakage. In cases where infection does occur, the hardware must be removed. PMID- 1621273 TI - Preparing for life after work. AB - 1. For retirement to be fulfilling and satisfying, hopes and dreams must be designed in early and middle adult life. Long before retirement, the adult must practice healthy living with the future in mind. 2. Saving and investing wisely is important and requires discipline and risk. A regular savings plan should start in the 30s and continue carefully throughout 2, 3 and 4 decades. 3. The transition to retirement is facilitated if interests are planned and friendships for retirement are cultivated in adult life. One of the best ways to prepare for retirement is to live the kind of life expected in retirement. PMID- 1621274 TI - Using the gold standard for OR instrument processing. PMID- 1621275 TI - Communication techniques. AB - OR managers become aware of vast amounts of information while carrying out job functions. It is important to use the information carefully and to select what information to share, when to share it, and with whom it should be shared. Appropriate communication can promote efficiency as well as job satisfaction. PMID- 1621276 TI - The OR experience during operation Desert Storm. AB - 1. Setting up an operating room from scratch tests basic OR knowledge. The usual high-technology equipment was absent in the desert. The hospital had to make due with the basics, including a bovie machine, suction machine, Gigli saw, minor orthopedic setup, and a basic laparoscopy set-up. 2. Much training focused on erecting and taking down the hospital; once the war began, urgency was a crucial factor. 3. The majority of the patients were Iraqi prisoners of war with shrapnel wounds to the abdomen, broken bones, and chest injuries; the Americans who were treated were seriously injured. Most of the procedures were orthopedic, thoracic, vascular, and general surgery cases. PMID- 1621277 TI - The demand for medical education in New York after World War II. PMID- 1621278 TI - Caring for the constitution: medical planning in revolutionary France. PMID- 1621279 TI - Every prospect of a healthy summer: the 1839 outbreak of yellow fever in Charleston, South Carolina. PMID- 1621280 TI - Making it. PMID- 1621281 TI - [Ultracytochemical study of adenylate cyclase activity in Hela cell culture exposed to fluorine]. AB - Electron microscopy has been used to study the adenylate cyclase activity in Hela cells after the incubation with 1.5 p. p. m. of fluoride for 5.30 and 60 minutes. It is established that the action of fluoride is accompanied by the increased enzyme activity in cell plasmalemma. Besides, the adenylate cyclase activity is revealed in the membrane of lipid droplets. In the mitotic cells a decrease of the enzyme activity in plasma membrane is observed parallel with its simultaneous increase in the metaphase chromosomes. PMID- 1621282 TI - [Effect of gene db dose on the development of beta-cytotropic and immunotropic effects of long-term glibenclamide administration in C57BL/KsJY mice]. AB - The studies have revealed a modifying influence of gene db on the expressivity of damaging beta-cytotropic effect of long-term sulphanilamide therapy and on the development of autoimmune cell response to antigens of pancreatic islets. It is substantiated as promising to study a significance of individual genes and their doses in determining the variations of reactivity to beta-cytotropic and immunotropic effects of the chemical nature factors. PMID- 1621283 TI - [Role of exogenous fibrinogen in the processes of degranulation of thrombocytes stimulated with thrombin. Ultrastructural study using fibrinogen labeled with colloidal gold]. AB - Using colloidal gold-conjugated fibrinogen (F-Au) it is shown that exogenous fibrinogen can participate in the platelet release reaction. In the absence of F Au, internal secretory vacuoles readily formed in human platelets stimulated with thrombin, but extrusion of their content was delayed. Upon incubation with F-Au, endocytic channels induced by F-Au-receptor interactions, fused with internal vacuoles, thus establishing spatial communications of the latter with the outer medium. PMID- 1621284 TI - [Current status and perspectives for genetic consultation and prophylactic medical examination of risk groups with malignant neoplasms of the female reproductive system and breast]. AB - It is shown as necessary to create specialized aid to cancer families in the general structure of oncological service. The results of 2-year clinical-genetic monitoring of high-risk group relative to ovarian, breast and endometrial cancer are presented. PMID- 1621285 TI - [Intensity of 3H-uridine incorporation in hepatocytes of various degrees of ploidy]. AB - The intensity of 3H-uridine incorporation, DNA content and number of nucleoli were measured in the same cells on charted preparations of isolated rat hepatocytes. It is shown that intensity of 3H-uridine incorporation and the number of nucleoli increases proportionally with the cell ploidy. PMID- 1621286 TI - [G. J. Meller in the USSR]. PMID- 1621287 TI - [Cytological features of the development of multi-organ failure induced by exposure of the body to tumor necrosis factor]. AB - Morphologic analysis of the changes in the internal organs after i.v. injection of 20 micrograms per mice of tumor necrosis factor (TNF) revealed the development of signs of multiorgan failure (interstitial and intraalveolar edema in the lung, acute fatty liver, tubular necrosis in kidney, brain edema) during first 24 h. The microvascular endothelial cells played a particular role in the state development. Results of investigation proved that endothelial cells were one of the major cellular targets for TNF action in vivo. PMID- 1621288 TI - Doppler ultrasound technique for measuring capillary-speed flow velocities with strong stationary echoes. AB - Ultrasound Doppler is widely used for low measurement in both medicine and industry, having the advantages of being non-invasive and comparatively simple and therefore inexpensive. The technique has not however been used for capillary blood flow measurement, because of the relatively low velocities encountered and because of the presence of strong interfering signals from the encompassing tissue. An ultrasound Doppler system capable of measuring flow velocities of one millimetre per second in the presence of one thousand times stronger interfering signals is described, as well as test results using both thread and flow phantoms. PMID- 1621289 TI - Prenatal diagnosis of cystic adenomatoid malformation of the lung in a twin pregnancy. PMID- 1621290 TI - An aluminium foreign body in the oesophagus. PMID- 1621291 TI - The air-fluidised bed in the management of chronic varicose leg ulceration. PMID- 1621292 TI - Breast lymphoma: fine needle aspiration biopsy. PMID- 1621293 TI - Eosinophilic fasciitis presenting as psoriatic arthropathy. PMID- 1621294 TI - Brain abscess ten years after penetrating glass injury to the skull. PMID- 1621295 TI - Pseudogout, chondrocalcinosis and the early recognition of haemochromatosis. PMID- 1621296 TI - Deliberate self-poisoning presenting at Craigavon Area Hospital: 1976 and 1986. AB - Deliberate self-poisoning presenting at Craigavon Area Hospital was compared in the years of 1976 and 1986. A decline in the use of benzodiazepines and increase in other agents, notably paracetamol, is reported. Alcohol is frequently associated with deliberate self-poisoning, while severe mental illness is less common. Diagnostic practice may have effects on bed occupancy in this group. PMID- 1621297 TI - The changing pattern of cervical cancer in Northern Ireland 1965-1989. AB - There was a change in pattern of an increased prevalence of cervical cancer in Northern Ireland from 1965 to 1989, characterised by an increased incidence in women under 40 years. These changes occurred despite special screening of younger women, although the screening programme has probably prevented an even greater increase in incidence of the disease. To reduce the incidence of cervical cancer, not only systematic screening but also cervical smears at more frequent intervals would be required. PMID- 1621298 TI - Renal transplantation in Northern Ireland 1968-1990. PMID- 1621299 TI - Educational supervision of pre-registration house officers. AB - An annual survey of the educational supervision of pre-registration house officers has been carried out since 1987 by the Northern Ireland Council for Postgraduate Medical Education and the Queen's University of Belfast. Educational supervision was considered by house officers to be unsatisfactory in 27% of medical posts and 52% of surgical posts. Regular teaching was provided at least weekly in 77% of the posts, but 50% of house officers wanted mor experience of managing common medical emergencies. Over one-third felt administrative duties were excessive. There is a strong argument that hospitals should designate within clinical units a consultant with responsibility for educational supervision of the pre-registration house officers. Creation of the hospital counterpart of the General Practitioner trainer--the educational supervisor--would enhance the educational value of the pre-registration year. This might avoid withdrawal of approval for training purposes from some pre-registration posts. PMID- 1621300 TI - Junior medical posts in the NHSSB: what the doctors think. AB - This survey of house officers in the Northern Health and Social Services Board in Northern Ireland demonstrated that they have complaints not just about the number of hours they work. Thirty-nine per cent noted poor standards of food and/or accommodation. Many complained about doing routine "non-medical" work and thought that their working conditions would be improved by nurses having more responsibility for managing intravenous medication and the employment of phlebotomists. Doctors expressed concerns about a lack of career counselling and availability of training in research methods in their posts. PMID- 1621301 TI - Acoustic neurinoma surgery in Belfast 1986-1989. AB - Forty-seven acoustic neurinoma tumours have been operated on in 46 patients in the years 1987-1989. This is a considerable increase over the prevalence in the preceding ten years. Twenty-six were classified as large tumours, 18 as medium and one was small. Surgical excision was complete in 16 and incomplete in 31 cases. Two patients died in the early postoperative period. Facial nerve function was preserved in 36 (80%) of cases; of these 27 (60%) had good function and nine (20%) fair function. Useful hearing was prevented in only two patients. The overall complication rate has been low and often of a transitory nature. PMID- 1621302 TI - Communication of discharge information for elderly patients in hospital. AB - The delivery of the discharge note to the general practitioners following discharge of elderly patients from a geriatric medical unit was studied over a two-month period. Handwritten discharge notes were received by the general practitioners in 75% of cases, and the delay was reduced to a median of two days by the use of a pre-printed envelope. Postal communications were also received by 89% of general practitioners after a median delay in two days. A dual system of hand-delivery and postal delivery would ensure faster and more complete receipt of information. PMID- 1621303 TI - A personal view of the hospital service. PMID- 1621304 TI - "Who fears to speak of ninety-eight"? PMID- 1621305 TI - Cinderella had a champion. PMID- 1621306 TI - The Royal Medical Benevolent Fund Society of Ireland. PMID- 1621307 TI - Central pontine myelinolysis without hyponatraemia. PMID- 1621308 TI - Radiation therapy in prostate cancer: whole pelvis with prostate boost or small field to prostate? AB - The purpose of this retrospective study is to identify prostate cancer patients who would benefit from pelvic nodes irradiation (whole pelvis) as opposed to the small-field irradiation to the prostate only. Between 1975 and 1983, 126 patients were treated by whole pelvis (4,600-5,000 cGY) with prostate boost (2,000 cGY) radiation (WP + P). Median follow-up was six years and six months. Comparison was made with historic control of 116 patients irradiated at the same institutions between 1971 and 1977 by small field to the prostate (P) to a dose of 7,000-7,500 cGY. There was a significant five-year survival improvement in the current WP + P radiation in Stage C (72% vs 40%, p = 0.0004) and Stage B (92% vs 70%, p = 0.025) but not in Stage A2 patients. However, WP + P radiation significantly improved disease-free survival (DFS) in only well and moderately but not in poorly differentiated carcinoma with a combined well and moderately differentiated five year DFS of 63 percent compared with the 45 percent in P radiation (p = 0.0228). Local tumor control was significantly improved in WP + P radiation in only Stage C cancers with their local recurrence rate 16 percent as compared with the 34 percent in P radiation (p = 0.0172). Although acute radiation reactions were more frequent in WP + P than P radiation (61% vs 41%, p = 0.0022), chronic radiation morbidity in both series were similar. Thus, whole pelvis with prostate boost radiation should be utilized in Stage B and Stage C cancers as this has shown to increase the survival of the patient without increasing chronic radiation morbidity. PMID- 1621309 TI - Fracture of penis: diagnosis and management. AB - Fracture of the penis is a rupture of the rigid corporeal body. Nine consecutive patients with this malady were managed by an operative repair, which included degloving of the penis, evacuation of the hematoma, and closure of the corporeal tear. Postoperatively all patients reported excellent rigidity of a straight penis. We conclude that operative management of a fractured corporeal body is safe and effective. PMID- 1621310 TI - Factors predicting efficacy of phentolamine-papaverine intracorporeal injection for treatment of erectile dysfunction in diabetic male. AB - Thirty-three diabetic men were instructed in the use of phentolamine-papaverine injections for the treatment of erectile dysfunction over a two-year period. Of these, 12 reported a satisfactory response and 21 reported a nonsatisfactory response. The responders and the nonresponders were retrospectively studied to identify characteristics that would predict a satisfactory response. No difference was found between the two groups in the duration of diabetes, the presence of retinopathy, neuropathy, nephropathy, peripheral vascular disease, or ischemic heart disease. The utilization of insulin, the prevalence of type II diabetes, or the use of drugs which would cause impotence, did not differ between the two groups. There was no difference in the serum testosterone levels between the two groups. Age was the only predictive factor. Only 1 of 14 patients over age sixty had a satisfactory response to treatment while 11 of 19 patients under age sixty had a satisfactory response. Five of the responders and 2 of the nonresponders proceeded to penile implant surgery and reported satisfactory results. While older diabetic men may choose a trial of intracorporeal injections, they should be counselled regarding the high failure rate and alternative forms of therapy. PMID- 1621311 TI - Extracorporeal shock-wave lithotripsy in hypertensive patients. Importance of pretreatment cardiac evaluation. PMID- 1621312 TI - Pressure response to rapid dilation of resting urethra in healthy women. AB - Rapid urethral dilations were performed by a balloon mounted on a double-tip transducer catheter for simultaneous measurement of pressure in urethra and bladder. The cross sectional area of the urethra was measured according to the field gradient principle. Pressure and cross sectional area were recorded synchronously. The response of the female urethra to rapid dilation is a typical stress relaxation effect with a pressure peak followed by a pressure decay over a few seconds. The peak pressure response represents the bladder pressure required in producing a corresponding urethral dilation by the ingression of urine. The increase in pressure response was statistically significant by increasing rate as well as size of dilation. The method enables experimental simulation of stress urinary incontinence in vivo which may bring further insight into the physiology of the urethral closure function and the pathophysiology of stress incontinence. For comparative studies rapid dilation should be performed under standardized circumstances. PMID- 1621313 TI - Solitary cerebellar metastasis from transitional cell carcinoma of bladder. AB - Brain metastasis from transitional cell carcinoma of the bladder is unusual, occurring most often in the presence of widespread systemic metastases. We report on a patient who presented with an isolated cerebellar metastasis and recurrent carcinoma of the bladder, after treatment with local excision and intravesical thiotepa. Further evaluation failed to demonstrate other distant metastases. Excision of the cerebellar lesion revealed transitional cell carcinoma identical to the original bladder tumor. In a review of the literature, we found reports of two similar patients in whom a solitary cerebellar lesion was the first sign of metastasis from carcinoma of the bladder; neither patient had evidence of other distant metastases, and neither previously had received systemic chemotherapy. These observations indicate that central nervous system metastasis from carcinoma of the bladder, while rare, should be considered in the differential diagnosis of solitary intracerebellar lesions in such patients. PMID- 1621314 TI - Massive retroperitoneal hemorrhage from adrenal gland metastasis. AB - We report an unusual case of spontaneous massive retroperitoneal hemorrhage from an adrenal gland metastasis. After medical therapy failed to stabilize the patient's condition, surgical exploration revealed a large retroperitoneal hematoma arising from a right adrenal gland metastasis. At the time of thoracoabdominal exploration in the lower lobe of right lung a small tumor nodule was palpated and resected. Pathologic examination of both lung and abdominal lesions revealed squamous cell carcinoma thought to have been primary in the lung. A review of the literature reveals that metastatic lesions to the adrenal gland are infrequently encountered clinically and rarely hemorrhage; the first such case in which massive retroperitoneal hemorrhage was a complication is reported in the urologic literature. PMID- 1621315 TI - Mycobacterium bovis vertebral osteomyelitis and psoas abscess after intravesical BCG therapy for bladder carcinoma. AB - Systemic complications of intravesicular BCG for bladder carcinoma are uncommon, and include fever, pneumonia, hepatitis, arthralgias, or skin rash. Local complications of BCG therapy for bladder cancer include cystitis, prostatitis, epididymo-orchitis, granulomatous lymphadenitis, or ureteral obstruction. We believe this is the first case of Mycobacterium bovis vertebral osteomyelitis and psoas abscess complicating intravesicular BCG therapy for bladder carcinoma. PMID- 1621316 TI - Extramedullary plasmacytoma (EMP) of urinary bladder. AB - An extramedullary plasmacytoma (EMP) is presented with an isolated lesion in the urinary bladder accompanying an IgG-K paraproteinemia. After a short-term oral melphalan administration, the tumor soon regressed together with the paraprotein, and has never recurred during the two-year follow-up. This is the fourth case of primary EMP of the urinary bladder reported in the literature. PMID- 1621317 TI - Computed tomography of primary transitional cell carcinoma of upper urinary tracts. AB - Preoperative computed tomography (CT) was utilized to evaluate 20 patients with primary transitional cell carcinoma of the upper urinary tracts. Of the 20 patients, 18 (90%) had CT visualization of the tumor as either a discrete mass or local ureteral and/or renal pelvic wall thickening; 2 (10%) had false-negative examinations. Seven of the 20 patients (35%) had CT evidence of tumor extension demonstrated by frank tumor invasion beyond the urothelium or by perirenal pelvic and/or periureteral fat streaks. Of the 4 patients with fat streaks, 2 (50%) had superficial tumors (T(A)T2), 1 had a T1 (25%) tumor, and 1 had a T3 (25%) tumor. All 3 patients with CT findings of direct extension of tumor through the wall of the ureter or renal pelvis had T3 tumors. Among the 13 with localized noninvasive tumor on CT, 5 (38%) had superficial tumors (TA, TIS, T1), 5 (38%) had T2 tumors, and 3 (21%) had T3 tumors. Of the 5 patients with enlarged regional lymph nodes (greater than or equal to 1.5 cm) on CT, 2 had tumor confirmed histologically, 2 had subsequent negative CT-guided biopsies, and 1 had a negative lymphadenectomy. Distant metastasis was discovered in 1 patient. The data suggest that when CT demonstrates direct tumor extension through the renal pelvic or ureteral wall, it is a sensitive indicator of high-stage disease. However, in the absence of this finding, CT is of limited value in staging patients with primary transitional cell carcinoma of the pyeloureteral system. PMID- 1621318 TI - Management of intraoperative penile erections with diluted epinephrine solution. PMID- 1621319 TI - Effects of multiple injections of HCG on testis blood flow. AB - In attempting to determine whether or not multiple injections of human chorionic gonadotropin (hCG) augment testis blood flow, adult male rats were injected with three doses of 10 IU of hCG every other day and testis blood flow was determined on day 5, the day of the final injection. Testis blood flow (mL/100 g testis tissue/min +/- SEM) as measured by the 133Xe washout method increased from 10.8 +/- 1.3 to 20.4 +/- 4.5 (p less than 0.05) after the three doses of hCG. These observations suggest that multiple injections of hCG appear to have the same effect as a single dose of hCG in increasing testis blood flow. This supports the hypothesis that hCG should be administered to all patients undergoing orchiopexy in the hope that the increased perfusion of the gonad will make it less susceptible to ischemia during the surgical procedure. PMID- 1621320 TI - Complications of enterocystoplasty. AB - Bladder reconstruction, either by augmentation or substitution enterocystoplasty, is a safe alternative to supravesical urinary diversion providing careful attention to preoperative selection, surgical technique, and postoperative review is observed. However, under the most optimal conditions an untoward outcome may occur. We reviewed our series of 100 intestinocystoplasties to categorize the types of complications encountered, and to identify preoperative risk factors that could potentially develop into an unfavorable sequela. Twenty-seven patients required either early or late surgical intervention, while 30 were managed nonoperatively. In our review we identified two groups, those with myelodysplasia and those with a solitary functioning kidney, who are at a higher risk for an unfavorable outcome to develop. PMID- 1621321 TI - Absorption of irrigating fluid during TURP. PMID- 1621322 TI - Ureteral stent removal sutures. PMID- 1621323 TI - [The relative risk of environmental exposure]. PMID- 1621324 TI - [Survival in HIV infection and AIDS]. AB - Duration of the AIDS-free period after HIV-infection and survival time vary to a wide extent. About 50 percent of the patients develop AIDS within 10 years. The most important prognostic factor is the CD4-lymphocyte count. The risk of AIDS increases significantly after CD4-lymphocyte counts drop below 400/microliters. Another prognostic factor is age. In older patients disease progresses more rapidly. AIDS often is preceded by an AIDS-Related-Complex characterized for example by Oral Candidiasis, Hairy Leukoplakia or Zoster of more than one dermatome. AIDS mostly develops 1/2 to 1 year after AIDS-Related-Complex. After AIDS is diagnosed the median survival time is not longer than 1 1/2 years. Single patients live much longer. Prognosis is influenced by the disease defining AIDS. Kaposi's Sarcoma often occurs early in the course of immunodeficiency and median survival is longer than after other opportunistic diseases. Survival also is longer after Pneumocystis Carinii Pneumonia since it is well treatable. A very short survival has been noticed after Non-Hodgkin-Lymphoma. During the last few years survival after HIV-infection and AIDS has been prolonged a little by sufficient prophylaxis of Pneumocystis Carinii Pneumonia which is the most frequent opportunistic disease, by antiretroviral treatment with Zidovudine and by increase of knowledge which makes early diagnosis and treatment of opportunistic diseases possible. PMID- 1621325 TI - [Administration of an HIV contaminated blood unit and hospital liability]. PMID- 1621326 TI - [Growth factors in therapy of life threatening leukopenia]. AB - We have tested granulocyte/macrophage-colony-stimulating-factor (rhGM-CSF, fully glycosylated, Sandoz, Schering/Plough) in 40 patients with chemotherapy-induced neutropenia. The drug enhanced leukocyte recovery in 5 different dose levels (2 32 micrograms/kg body weight) if given by continuous intravenous infusion or subcutaneously for 5 days. Patients who received rhGM-CSF during neutropenic infections (n = 32) survived significantly better if they recovered leukocytes to at least 1.5 x 10(9)/l. In patients with myelodysplastic syndromes and excess of blasts (n = 82) remission could be induced in nearly 50% if the drug was given together with low dose cytosine arabinoside (LD-AraC). The results of these phase II-studies show that rhGM-CSF is a safe drug which may save many patients from life-threatening situations during haematopoietic insufficiency. PMID- 1621327 TI - [The prognosis of conservatively treated lumbar intervertebral disk displacement]. AB - 72 out of 120 patients who where treated conservatively for proven lumbar disc prolapse over a seven-year-period were reexamined. Questionnaires could be obtained and evaluated for 91 patients. The date of reexamination was an average of 44.5 months after the end of inpatient-treatment. Results are given for the duration of inability to work and the "return to work" (RTW)-rate. The ability to work of 54 patients was regained after an average of 11.1 weeks, 95% of patients could return to their previous workplace. PMID- 1621328 TI - [Rehabilitation of the aged]. AB - It is common knowledge that in the light of demographic and social developments in the years to come our society will have to rise to the enormous challenge of medical care for the old, sick and needy. In order to shorten long-time nursing periods for old people in need of medical care preventive treatment and medical rehabilitation must be the main priority of all measures. Geriatric rehabilitation is subdivided into prophylactic rehabilitation (medical care, social sector), general rehabilitation and target-specific rehabilitation. Both the rehabilitation team and the motivation to rehabilitate are of particular importance during geriatric rehabilitation. On the whole, it has to be reckoned that older people need a distinctly longer period of recuperation, in which the clinical picture rather than the age is the decisive factor of a successful rehabilitation. As for Germany, that is only the beginning of stationary geriatric rehabilitation. PMID- 1621329 TI - Classification of 1,198 cases of bovine lymphoma using the National Cancer Institute Working Formulation for human non-Hodgkin's lymphomas. AB - A retrospective histologic study was made of 1,198 cases of bovine lymphoma using the National Cancer Institute Working Formulation for human non-Hodgkin's lymphoma. This classification scheme was found to be readily applicable to bovine lymphoma. Most of the cell types described in the National Cancer Institute Working Formulation occurred in this series of bovine lymphomas, but the distribution of cell types varied markedly compared to that of human beings. Eighty-nine percent (1,067/1,198) of bovine lymphomas were high-grade tumors. The diffuse large cell type and its cleaved variant comprised 65.9% of all bovine lymphomas. Similar to the dog, but in marked contrast to human beings where at least 34% of non-Hodgkin's lymphomas were follicular, follicular tumors were found to be extremely rare in cattle (0.3% or 4/1,198). The prevalence of cell types varied significantly between the enzootic and sporadic lymphomas. The cleaved variant of the diffuse large cell type constituted 38% (406/1,072) of enzootic lymphomas versus 14% (18/126) of sporadic lymphomas. The mitotic index (100 x oil immersion field, 175 microns in diameter) of enzootic lymphomas (3.72 +/- 0.06, mean +/- standard error) was significantly greater than the mitotic index of sporadic lymphomas (2.82 +/- 0.17). We concluded that the cleaved variant of the diffuse large cell type with high mitotic index is characteristic of enzootic lymphoma. This characteristic high-grade cell type may be a consequence of the viral etiology of the enzootic form of bovine lymphoma. PMID- 1621330 TI - Intracranial meningioma with pulmonary metastasis in three dogs. AB - Extracranial metastasis of primary central nervous system neoplasms is uncommon and has not been described in the dog. We report the clincopathologic features of intracranial meningioma with pulmonary metastasis in three dogs (case No. 1: 13 year-old castrated male Boxer dog; case No. 2: 14-year-old spayed female Dachshund; case No. 3: 6-year-old spayed female German Shepherd Dog). Case No. 1 presented with ataxia, lethargy, vomiting, and leaning and falling to the right, and had a transient remission following radiation and corticosteroid therapy; case No. 2 had a history of seizures that were unresponsive to primidone, left sided postural reaction deficits, ataxia, and circling to the right; case No. 3 had only intermittent episodes of vomiting Computed tomography of case Nos. 1 and 2 revealed peripherally located homogeneous contrast-enhancing intracranial masses. Postmortem examination revealed intracranial masses with single or multiple pulmonary nodules in all three cases. Histologically, the intracranial and pulmonary masses were meningotheliomatous meningiomas with atypical features including brain infiltration, necrosis, nuclear atypia, prominent nucleoli, and moderate cell density. All of the primary meningiomas had low mitotic rates. The current interest in early diagnosis and aggressive clinical/surgical management of canine patients with meningioma and other primary central nervous system neoplasms will likely result in an increased detection of extracranial metastases. PMID- 1621331 TI - Ultrastructural findings in congenital anemia, dyskeratosis, and progressive alopecia in Polled Hereford calves. AB - Ultrastructural evidence of dyserythropoiesis was found in ten calves (ages 1 to 16 months) previously diagnosed as having congenital anemia, dyskeratosis, and progressive alopecia. Morphologic abnormalities found in erythroid precursors of all calves were associated with the nucleus. Rubriblast nuclei were irregular with numerous blebs, indentations, and deep clefts. Elongated blebs appeared as satellite nuclei in some sections. Nuclear membranes had numerous defects or gaps, which were frequently present in, but not limited to, recently divided cells. Cytoplasmic material could be found within these gaps and extending into the nucleus. Rubricytes had chromatin that was abnormally condensed and hyperosmiophilic, with numerous translucent vacuoles present. Binucleate rubricytes occurred frequently in affected calves. These changes resemble those of type I congenital dyserythropoiesis in human beings, and we suggest congenital anemia, dyskeratosis, and progressive alopecia of Polled Hereford calves as the appropriate diagnostic terms to describe this disease. PMID- 1621332 TI - Vascular lesions in lungs of Bali cattle with Jembrana disease. AB - Jembrana disease is an acute infectious disease of unknown etiology enzootic among Bali cattle (Bos javanicus) in Indonesia. Morphologic examination of 75 female Bali cattle between 18 months and 4 years old affected with Jembrana disease consistently revealed pulmonary granulomatous vascular lesions. The lesions were diffusely distributed throughout the lung. The principal lesion was the presence of a large number of intravascular macrophages that filled the lumina of pulmonary veins and pulmonary arteries of a vascular diameter of 20-200 microns, excluding the rest of blood cellular components. Concentric layers of perithelial cells also with plasma cells and macrophages were occasionally present around both veins and arteries. Infiltration of polymorphonuclear leukocytes or small lymphocytes was not seen. Destruction or necrosis of tissues or blood vessels was rarely seen. Because this vascular lesion was found in the lungs of all affected cattle examined, this change is useful for the postmortem diagnosis of Jembrana disease. Moreover, its presence could be used to distinguish Jembrana disease from malignant catarrhal fever and other lymphoreticular proliferative conditions that are frequently found among cattle in Indonesia. PMID- 1621333 TI - Transplantation of large granular lymphocyte leukemia in congenitally athymic rats. AB - Twenty-two congenitally athymic nude (rnu/rnu) rats were transplanted with large granular lymphocyte leukemia derived from F344 rats and then compared with ten similar rats inoculated with a suspension of normal F344 rat spleen cells. The normal spleen cells and tumor cells from a spontaneous, naturally occurring leukemia did not grow or cause clinical disease in any of the rats. All rats inoculated with a serially passaged leukemia cell inoculum had local growth at the inoculation site that spread widely and resulted in progressive tumor growth. Death occurred between 16 and 38 days after inoculation. The 22 rats that received passaged tumor cells developed leukemia and splenomegaly. Spleens were diffusely infiltrated by tumor cells and had severe depletion of lymphocytes in the white pulp. Leukemic rats were thrombocytopenic and had hemolytic anemia characterized by increased osmotic fragility, red cell width, and many nucleated erythrocytes. The disease syndrome appears similar to that of F344 rats transplanted with the same inoculum. Because the host rats lacked T cells, it is concluded that the hemolytic anemia and thrombocytopenia that develop in transplanted rats are independent of T cell function. PMID- 1621334 TI - Ultrastructural changes in articular cartilages of immature beagle dogs dosed with difloxacin, a fluoroquinolone. AB - The ultrastructural features of quinolone-induced arthropathy were studied in the humeral and femoral heads of nine skeletally immature Beagle dogs (3 months old) that were dosed orally with difloxacin at 300 mg/kg body weight and euthanatized 24, 36, or 48 hours later in groups of three. Three age-matched dogs were given a placebo and euthanatized after 48 hours. Mitochondria in chondrocytes had significantly greater cross-sectional areas (P less than 0.05) in electron micrographs from dogs euthanatized after 48 hours of treatment than did those in other groups. There was also a significantly greater percentage of chondrocytes with swollen mitochondria in treated dogs than in the controls (P less than 0.05). These changes preceded the necrosis observed in some chondrocytes in the dogs of the 48-hour group. Disruption of extracellular matrix was first observed in the pericellular matrix of necrotic chondrocytes, indicating that this change was secondary to the changes in chondrocytes. Fissures within cartilages apparently resulted from the loss of the normal association of proteoglycans with collagen fibrils. PMID- 1621335 TI - Colonization of the small intestine of weaned pigs by enterotoxigenic Escherichia coli that lack known colonization factors. AB - Intestinal colonization of 3-week-old weaned pigs by enterotoxigenic Escherichia coli (ETEC) strains that were originally isolated from weaned pigs with fatal diarrhea and that lacked K88, K99, F41, and 987P adhesins (4P- ETEC) was studied by histologic, immunofluorescent, and electron microscopic techniques. In the first experiment, 16 principal pigs were inoculated orogastrically with ETEC strain 2134 (serogroup O157: H19) or 2171 (serogroup 0141:H4), and eight control pigs were not inoculated. In the second experiment, 24 principals were inoculated with ETEC strain 2134, and 12 controls were inoculated with a nonenterotoxigenic strain of E. coli. Principal and control pigs were necropsied at intervals from 24 to 72 hours after inoculation of principals to provide the tissues used for this report. Results from the two experiments and with both ETEC strains were similar and therefore were combined. Adhesion by 4P- ETEC was demonstrated in ileum but not in cecum or colon in 22/40 principal pigs sampled at 24 to 72 hours after orogastric inoculation. Adherent bacteria were most apparent on the intestinal villi covering Peyer's patches. Only occasional adherent bacteria were detected in ileal sections from a few (4/20) of the control pigs. Adherence by 4P ETEC was characterized by "patches" of bacteria closely associated with the lateral surfaces and less frequently with the tips and the bases of intact villi. In most cases, the adherent bacteria were separated from epithelial cell microvilli and other bacterial cells by a 50-400-nm space. Filamentous bacterial appendages bridged this space and formed a network among adjacent bacteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621336 TI - Epicardial and corneal mineralization in clinically normal severe combined immunodeficiency (SCID) mice. PMID- 1621337 TI - Ultrastructure of lipid storage cells in the adrenal cortex and the ovary in female Mastomys (Praomys coucha). PMID- 1621338 TI - Desmin and vimentin immunocharacterization of feline muscle tumors. PMID- 1621339 TI - Multicentric lymphosarcoma associated with pulmonary adenomatosis (Jaagsiekte), pulmonary lymphoid hyperplasia, and lymphoid interstitial pneumonia in a ewe. PMID- 1621340 TI - Eosinophilic-mastocytic arteriolofibrosis in a cow. PMID- 1621341 TI - Congenital urinary incontinence in cats: a review of 19 cases. AB - Nineteen cases of feline congenital urinary incontinence (10 cats with ureteral ectopia and nine with incompetence of the urethral sphincter mechanism) are reviewed. The 10 cats with ureteral ectopia are considered together with 13 from previous reports. There was no apparent breed predisposition. Most of the 23 cats were presented for urinary incontinence but two of them were continent. Thirteen were females and ectopia was unilateral in 13 and bilateral in 10. Twenty-eight of 31 ectopic ureters terminated in the urethra. The commonest complication was hydroureter/hydronephrosis (10 cases). Eighteen of the cats were treated surgically, 13 by ureteral transplantation, four by ureteronephrectomy and one by ligation of the renal blood vessels; 16 of them were cured by surgery. Congenital urethral sphincter mechanism incompetence has not been reported previously in the cat. Nine cases are presented and the urethras of all were markedly hypoplastic. A common concomitant abnormality was vaginal aplasia, with the uterine horns terminating in the dorsum of the bladder. Bacteriuria was more common in this group than in the cats with ureteral ectopia. PMID- 1621342 TI - A microlarval development assay for the detection of anthelmintic resistance in sheep nematodes. AB - A microlarval development test for the detection of anthelmintic resistance in nematodes is described. Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus colubriformis eggs were cultured to third stage larvae in the presence of Earle's balanced salt solution, yeast extract and bacteria in a total volume of 150 microliters. Good dose-response data were obtained with thiabendazole, levamisole, pyrantel tartrate and ivermectin allowing the determination of the 50 per cent lethal concentration and of resistance factors when resistant strains were available. The test was found to be accurate, sensitive, easy to carry out and applicable to the routine detection of resistance. PMID- 1621343 TI - Isolation of Leptospira interrogans from kidneys of Zimbabwe beef cattle. AB - Four hundred and eighty bovine kidneys were collected from an abattoir near Harare between December 1987 and November 1988, and leptospires were recovered from 50 (10.4 per cent) of them. The isolates were identified to serogroup level by the microscopic agglutination test; 32 belonged to serogroup Sejroe, seven were Pyogenes, four Hebdomadis, two Tarassovi, and one isolate each belonged to serogroups Australis, Bataviae, Grippotyphosa, Icterohaemorrhagiae and Pomona. PMID- 1621344 TI - Unusual mass mortality of juvenile kittiwakes (Rissa tridactyla). PMID- 1621345 TI - Anti-canine distemper virus antibodies in common and grey seals. PMID- 1621346 TI - Use of a transcervical technique for embryo recovery in sheep. PMID- 1621347 TI - Crenosoma vulpis infection in a dog. PMID- 1621348 TI - Care of wild and non-domestic species. PMID- 1621349 TI - Importance of benzimidazole-resistant Ostertagia circumcincta. PMID- 1621350 TI - Use of Xylocaine pump spray for intubation in cats. PMID- 1621351 TI - Chronic superficial keratitis in German shepherd dogs. PMID- 1621352 TI - Ovarian fusion in ewes. PMID- 1621353 TI - Placental transfer of fluoride in Holstein cows. AB - Placental transfer of fluoride was studied in 40 Holstein cows and related to a previous 7 1/2 y study for comparative purposes. Animals were randomly assigned to fluoride dosage groups of control, 0.51, 1.31 or 2.66 sodium fluoride/d (10, 25, 50 or 100 ug/g feed). Each animal received the dose daily via gelatin bolus for 4-14 d prior to parturition. Maternal heparinized blood samples were collected before dosing and after parturition. Placental cotyledon and calf blood samples were collected from each animal immediately after parturition. Maternal and calf plasma and placental cotyledon fluorine concentrations were determined. Increased levels of fluoride given to pregnant cows resulted in significantly increased (p less than 0.05) maternal plasma and placental cotyledon fluorine concentrations. Calf plasma fluorine concentrations at birth did not significantly increase in relation to the fluoride treatment level of dams. The data support the concept that under normal circumstances in cattle there is a partial placental barrier to fluoride that operates to limit fluoride concentrations in the fetal circulation and tissues. PMID- 1621354 TI - Parathion transfer and acetylcholinesterase activity in an in-vitro perfused term human placenta. AB - Organophosphate transport through the placenta was investigated in an in-vitro placental perfusion system. The system consisted of maternal and fetal reservoirs in which Krebs Ringer bicarbonate buffer with heparin, albumin and glucose was circulated at a constant pH, temperature and pO2. Parathion was analysed by means of gas chromatography with a N-P detector. 14C Antipyrine, a lipid soluble salt, was used as an internal standard, which allowed for the difference in placental size and permeability. A certain amount of parathion passed the placenta and reached the fetal compartment. Glucose consumption was not influenced by the introduction of parathion; neither was the water content of the placental tissue. Acetylcholinesterase activity in placental tissue decreased 50%. The amount of parathion transferred was not negligible and could have caused damage to a fetus. PMID- 1621355 TI - Container residue after activated charcoal administration in the emergency department. AB - We hypothesized that sources of activated charcoal (AC) used as a form of gut decontamination in the treatment of drug overdose may deliver significantly less charcoal than expected because of retained charcoal and sorbitol (ACS) from the treatment of 50 consecutive overdose patients were collected. Health care personnel delivering the dose were unaware of the study hypothesis. A total of 82 containers were obtained in this manner. Each container was labelled to contain 25 g AC and 48 g sorbitol. Five unused containers of ACS were obtained as controls. Each container was thoroughly cleaned, and the contents vacuum filtered and washed with 1 L of tap water. The tared filter paper and charcoal was dried for 24 h and weighed. The average amount of charcoal retained in each used container (retained) was 0.549 g (range 0.318-1.637 g). This accounts for 2.2% of the 25 g dose expected to be delivered. The average amount of charcoal found in each unused container (actual) was 25.892 g. The delivered dose (actual minus retained) may be calculated as 101.4% of the expected 25 g dose. When using this formulation of ACS there is no significant difference between the amount of charcoal given to an overdose patient and the amount ordered for gut decontamination. Despite the poor suspension of charcoal in sorbitol and the less than ideal conditions under which it is given, the patient receives an adequate dosage of AC if it is ordered. PMID- 1621356 TI - Subacute toxicity of paraquat in beagle dogs: clinicopathology and pathologic examinations. AB - Beagle dogs were allocated to 4 groups, each consisting of 3 males and 3 females, which received 0.055, 0.165 or 0.495 mg paraquat (PQ)/kg/day sc for 4 w to investigate subacute toxicity. Recovery 4 and 8 w postadministration was studied. In the early stage there was vomiting, decreased activity and undernourishment. Induration and ulcers at the injection sites were seen. The group receiving 0.495 mg PQ/kg had reduced food ingestion and occasional decreases in water consumption until the end of the 4-w injection period. Three animals in the 0.495 mg PQ/kg group were sacrificed in the moribund stage with marked decreases in body weight. Ophthalmologic examination at 4 w of recovery detected hemorrhage around the nasalis vein of the left fundus in 1 animal that received 0.495 mg PQ/kg. No abnormal changes in electrocardiography (ECG) were noted throughout the experimental period. Slightly increased urinary protein, reticulocyte counts, and fibrinogen were observed in a few animals in each group. A few animals that received 0.165 or 0.495 mg PQ/kg had increased phospholipid, blood urea nitrogen, and creatine phosphokinase. The lungs of the moribundly sacrificed animals had moderate atelectasis, localized atelectasis, moderate thickening of alveolar wall and pleura, proliferation of fibroblast-like cells, and abundant fibers in interstitium and alveoli. In the liver there was slight hemorrhage along the gallbladder. On electron microscopy of the lung, proliferation of fibroblasts, myofibroblasts and type II alveolar cells, and some mast cells were observed in thickened alveolar walls. Abundant collagen fibers, destroyed cell debris and mitotic figures of spindle-shaped fibroblasts were also observed in the dilated interstitium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621357 TI - The effects of administering methylmercury in combination with ethanol in the rat. AB - Methylmercury (MeHg) is a potent neurotoxicant and nephrotoxicant in several animal species including humans. Although the in vivo toxicity of MeHg per se is well known, the interaction between MeHg and other pollutants and with nutritional factors is not well understood. Since ethanol (EtOH) is a widely consumed toxicant which has been shown to enhance the histopathologic effects of MeHg on renal tissues, a study was undertaken to examine the effects of the combined administration to rats of MeHg and EtOH on renal function and on mercury distribution in body tissues. Forty-eight rats were divided into 6 treatment groups of 8 rats each. Rats in groups 1, 2 and 3 were given feed ad libitum, a restricted liquid diet of 70 mL/d or distilled water orally, respectively. Rats in groups 4, 5 and 6 were given 1.5 mg MeHg/kg bw, 2.0 g EtOH/kg bw, or 1.5 mg MeHg + 2.0 g EtOH/kg bw, respectively, by oral gavage daily for 45 d. All rats except those in group 1 (ad libitum) were fed 70 mL of liquid diet/d for the entire study period. The ingestion of MeHg + EtOH in combination induced a greater increase in renal weight compared to treatment with either MeHg + EtOH alone. Only those rats given MeHg in combination with EtOH exhibited oliguria and elevated blood urea nitrogen levels. Despite this antidiuresis, urinary concentrating ability was impaired in those rats given both MeHg and EtOH. In contrast, the ingestion of MeHg by itself caused the most rapid loss of glucose in urine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621358 TI - Case reports of lead poisoning in dogs from the National Animal Poison Control Center and the Centre National D'Informations Toxicologiques, Veterinaires: anecdotes or reality? AB - This paper presents case reports of lead toxicoses from 2 major animal poison control centers in Europe and North America, gathered from 1985 through 1989. All results examined here involved cases assessed as "toxicosis" or "suspected toxicosis" by the National Animal Poison Control Center (NAPCC) or the Centre National d'Informations Toxicologiques Veterinaries (CNITV). 537 cases were reported to the NAPCC, most of them concerning dogs (59%). In France, most of the 362 cases involved cattle (57.2%). There was an increased number of cases reported during late summer and early fall, and a decreased number of cases in November and December, in both centers. Dogs intoxicated were predominantly young animals (60% were less than 2 years old). No sex difference was noted. Pure bred dogs appeared more often involved than mixed-breed ones, but the breed distribution closely resembles dog breed distribution in the US. The source of lead was usually unknown and, when information was available, paint seemed to be the most common cause of poisoning. Clinical signs reported to the animal poison control centers involved the CNS and GI tract. Results from the French and the American database showed similar trends. They are compared to data from veterinary clinics and veterinary colleges in the US and Australia. In each case, data are very similar to what was reported to the CNITV and the NAPCC. It is concluded that animal poison control centers databases can provide a useful tool for better knowledge of animal poisoning. They can also help identify unexpected toxicologic problems related to drug administration or pesticide use. PMID- 1621359 TI - Effect of vitamin B6 supplementation on gentamicin nephrotoxicity in rabbits. AB - Therapeutic use of gentamicin (GM) in a clinical setting may result in nephrotoxicity, most commonly presenting as acute tubular necrosis (ATN). We have previously observed decreased plasma pyridoxal 5'-phosphate (PLP) levels in rabbits given therapeutic doses of GM and endeavor in this study to determine if vitamin B6 supplementation (B6S) could protect against the nephrotoxicity of GM. Twenty-one rabbits were randomly assigned to 1 of 7 treatment groups of 3 rabbits each. Three of the groups received 10 mg GM/kg with either 10 mg B6S, 100 mg B6S or 0.9% saline. Three of the groups received 40 mg GM/kg with either 10 mg B6S, 100 mg B6S, or normal saline. The control group only received 100 mg B6S. All treatments were administered im once daily for 5 d. Blood was drawn for chemical assays on day 0 prior to any treatments and 2 h after each respective treatment on days 1, 3 and 5. After 5 d, the rabbits were euthanatized and kidneys were excised for histological evaluation by light microscopy. At the 40 mg GM/kg/d dose, significant mild to moderate ATN was observed in the saline controls, which was prevented by either dose of B6S. Only a few animals given 10 mg GM/kg/d showed any renal pathology and that was minimal. Unexpectedly, 1 rabbit given only 100 mg B6S/d but no GM had interstitial nephritis with focal ATN. We conclude that vitamin B6 can protect against the nephrotoxicity of GM in rabbits, but that further study is needed on the possible nephrotoxicity of high doses of B6S. PMID- 1621360 TI - The toxicokinetics of 1,3-butylene glycol versus ethanol in the treatment of ethylene glycol poisoning. AB - Ethylene glycol (EG) is a toxic chemical found in antifreeze and heat exchangers. Standard therapy for EG intoxication in administration of ethanol (ETOH) to inhibit its metabolism by alcohol dehydrogenase (ADH). Studies indicate 1,3 butylene glycol (BG) binds to ADH more efficiently than EG and is orally less toxic than EG or ETOH. Male rats were divided into 5 groups of 6 animals. Groups received by oral intubation a single dose of EG (32 mmole/kg), BG (39 mmole/kg) initially and every 6 h up to 72 h, ETOH (39 mmole/kg) initially and every 6 h up to 72 h, or EG initially and then either BG or ETOH every 6 h up to 72 h. Administration of ETOH produced hepatotoxicity and pulmonary pathology as indicated by changes in clinical chemistry, urinalysis, and histopathology, while BG did not. Neither ETOH nor BG produced any apparent nephrotoxicity. ETOH produced ataxia, lethargy and central nervous system depression while BG did not. BG produced a higher concentration of urinary EG indicating a better inhibition of ADH metabolism of EG. Ethanol produced a higher EG blood concentration than BG. Ethanol's higher EG blood concentration may be partially attributed to dehydration and a decreased urine output as well as inhibition of ADH metabolism. Ethanol produced mortality in all animals prior to 72 h. The EG/ETOH combination produced mortality more quickly due to additive toxicity of the combination. Lack of any significant toxicity produced by BG and the production of significant toxicities by ETOH indicates that BG is potentially a better antidote than ETOH. PMID- 1621362 TI - Inhibition of DNA synthesis and decreased reproductive capacity in cattle maintained on semi-arid rangeland with Acacia species as a major component of available browse. AB - The ability of bovine lymphocytes to initiate in vitro blastogenesis in response to mitogen stimulation or to initiate DNA excision repair after treatment with a mutagen was evaluated as a function of the differing environmental conditions under which donor animals were maintained. Crossbred Brahman-Hereford F1 females were held on either a humid, coastal bermudagrass, improved pasture at Overton, TX, or in low or high grazing pressure herds on a semi-arid rangeland (Acacia dominated shrubland) at Uvalde, Tx. Peripheral blood lymphocytes (PBL) from these animals were examined to determine their in vitro ability to engage in phytohemagglutinin (PHA)-stimulated blastogenesis and to initiate excision repair of DNA damage after exposure of the cells to the model polynuclear hydrocarbon carcinogen 7,8-dihydrodiol-9, 10-epoxy-benzo(a) pyrene (BPDE). PBL from cattle at both locations were compared, with significantly decreased blastogenesis and DNA excision repair observed in PBL from Uvalde high grazing pressure cattle. Cattle in the Uvalde high grazing pressure herd also exhibited significantly decreased reproductive efficiency. The data indicate that ingestion of sufficient quantities of palatable, but toxic, forage species available at the Uvalde test site is sufficient to decrease DNA synthesis associated with either mitogen stimulated blastogenesis or DNA excision repair in bovine PBL, and suggest that the reduction in PBL DNA synthesis may be correlated with the changed reproductive efficiency in animals ingesting an increased ratio of forage from Acacia species. PMID- 1621361 TI - Dermal exposure of hexachlorophene to guinea pigs. AB - The skins of guinea pigs were exposed to 50 mg/kg hexachlorophene (HCP) for 7, 15 or 30 days. The activities of skin marker enzymes (beta-glucuronidase, histidase, tyrosinase) increased, but glutathione decreased. Lipid peroxidation and histamine contents increased during different time intervals. The histopathological changes showed damage to epidermis and dermis. Depending on the duration of exposure, HCP produces biochemical and histopathological damage to skin. PMID- 1621363 TI - Aesculus glabra intoxication in cattle. PMID- 1621364 TI - Toxic epidermal necrolysis associated with flea dips. AB - A 5-y-old intact female Himalayan cat was dipped with an organophosphate-based compound for flea infestation. The animal subsequently died of organophosphate intoxication. Skin lesions present at necropsy were diagnosed microscopically as toxic epidermal necrolysis. A 5-y-old spayed female Corgi dog was dipped with a d limonene-based compound for flea infestation. The dog subsequently developed a bullous skin disorder which rapidly progressed to severe coalescing necrotizing dermatitis with large areas of skin sloughing. The dog was treated for a tentative diagnosis of toxic epidermal necrolysis with a short course of corticosteroids and extensive supportive care and recovered completely. Flea dip preparations have the potential to induce severe immune-mediated dermatopathies such as toxic epidermal necrolysis. PMID- 1621365 TI - Emergency department external decontamination for hazardous chemical exposure. AB - Although external decontamination is an integral aspect of the emergency management of hazardous chemicals exposure, no standard protocol or report of human experience is available. We performed a retrospective review of all patients decontaminated in our emergency department over a 6-y period for hazardous chemicals exposure. Patients were treated by a universal substances protocol in a specially designed decontamination area. Ocular irrigation utilizing 1500 ml of normal saline po was employed in 27 patients. Oral mucosal irrigation utilizing 1500 ml water was employed in 2 patients. All 72 patients received skin and hair decontamination. Skin was washed 3 times with detergent and cornmeal mixture, and water irrigation or shower for 3 min. Hair was shampooed 3 times with mild soap for 3 min. A subset of patients (n = 31) received pre-decontamination and post-decontamination skin swabbing. Swabs were analyzed by a certified analytical chemistry laboratory utilizing gas chromatography/mass spectrometry. Positive pre-decontamination swabs were seen for pesticides and PCBs. All post-decontamination swab analyses were negative, indicating that the method utilized was effective. PMID- 1621366 TI - Bitter cassava poisoning in eight children: a case report. AB - Bitter cassava poisoning in 8 children is reported. The incidence of bright cherry-red blood is emphasized. These patients were in bad condition, but they survived although they received different therapies. Four of them were treated with sodium nitrite and thiosulfate and the remainder with hydroxocobalamin alone. This latter drug may be useful in less severe circumstances. PMID- 1621367 TI - The veterinary importance of the toxic syndrome induced by ionophores. AB - Monensin, lasalocid, salinomycin, narasin and maduramicin are carboxylic ionophores intended for use as anticoccidial drugs for poultry and as growth promotants for ruminants. Generally, ionophores have been found safe and effective in the target animals receiving recommended dosage levels. However, toxic syndromes can result from overdosage and misuse situations. More information and reports of adverse reactions are available for monensin than the other ionophores because of monensin's longstanding and widespread use in the poultry and livestock industries. Care must be exercised in the diagnosis of ionophore toxicoses since clinical signs and lesions are not pathognomic. However, a feed-related problem characterized clinically by anorexia, diarrhea, dyspnea, ataxia, depression, recumbency and death, and pathologically by focal degenerative cardiomyopathy, skeletal muscle necrosis, and congestive heart failure may warrant a presumptive diagnosis of ionophore toxicity. Confirmatory diagnosis will require considerations of differential diagnoses and laboratory assays to determine the specific ionophore involved. Presently, there is no antidote or treatment for toxicoses induced by the ionophores. Judicious use, avoidance of overdosing, and adherence to species recommendation will help prevent the occurrence of adverse effects associated with this class of compounds. PMID- 1621368 TI - Lack of effectiveness of several chelators in removing internally deposited strontium from mice following repeated parenteral strontium administration. AB - Diethylenetriaminepentaacetic acid (DTPA), ethylenglycolbis-(beta-amino ethylether)-N,N-tetraacetic acid (EGTA), tartaric acid, KRYPTOFIX 222, and KRYPTOFIX 5 were evaluated for their efficacy in mobilization of strontium from the body of mice which had received 20 sc injections of strontium nitrate (95 mg/kg/injection) for 4 w. Twenty-four hours after the last strontium injection, ip administration of 1 of the various chelators or 0.9% saline was initiated and continued daily for 5 d. Mice were housed in metabolic cages, and urine and feces were collected daily for 5 d. After this period, the animals were killed and tissues removed. Tartaric acid, KRYPTOFIX 222, and KRYPTOFIX 5 had no effect on urinary or fecal strontium elimination, whereas DTPA and EGTA significantly decreased the fecal strontium excretion. The concentration of strontium in bone was only lowered in tartaric-treated mice. This study indicates the use of the above chelators is not an effective treatment to enhance the removal of strontium following repeated parenteral strontium administration. PMID- 1621369 TI - A review of toxicity factors in some food and feedingstuffs in the nutrition of man and livestock in Nigeria. AB - A review of the toxicity factors in some food and feedingstuffs in the nutrition of man and livestock in Nigeria was conducted. The crops reviewed were cassava, cocoyam, guinea corn, cottonseed, soyabean, bambara, groundnut and cowpea. These crops provide cheap sources of carbohydrate and protein in the diets of humans and livestock. However, antinutritional factors inhibit their use. Antinutritional or toxic factors associated with them are reviewed and means of detoxifying them for human and livestock feeding are enumerated. PMID- 1621370 TI - [Vitamins and endogenous regulatory factors]. PMID- 1621371 TI - [Status of nitrogen metabolism in reducing-diet therapy]. PMID- 1621372 TI - [Effectiveness of diet therapy in patients with ischemic heart disease and a history of myocardial infarction at young age]. AB - To elucidate the effect of dietetics on the onset and course of coronary heart disease (CHD) patients who survived myocardial infarction at young age were investigated. The analysis of clinical and metabolic changes, psycho-vegetative disorders permitted the authors to distinguish two groups of patients: group 1- patients with normal body mass, and group 2--those with excessive body mass who received, respectively, A1 (basic) and Ar (reduced) variants of theanti- arteriosclerotic diet. It was established that the Ar diet produced positive effects on the dynamics of body mass reduction, on the cardiovascular system, on parameters of lipid metabolism, hemostasis and psycho-physiologic parameters of group 2 patients. Diet therapy combined with tranquilizers is recommended for group 1 patients. PMID- 1621373 TI - [Effect of food on blood levels of insulin, glucagon and C-peptide in gastroduodenal pathology]. AB - Insulin, glucagon and C-peptide content in the blood was assayed with the use of commercial radioimmune kits (Diagnostic, USA, and Oris, France). A total of 93 peptic ulcer patients (35 with duodenal peptic ulcer, 28 with gastric ulcer, 16 after Billroth-I resection, and 14 after Billroth-II resection) and 25 patients with chronic gastritis attended by secretory insufficiency were investigated. The study was conducted on empty stomach and after a test breakfast containing 57 g of protein, 63 g of fat, 103 g of carbohydrates that comprised 1212 kcal. The highest changes in hormone incretion were recorded in patients with peptic ulcer disease after Billroth-I and Billroth-II resection, the lowest--in patients with chronic gastritis attended by secretory insufficiency. PMID- 1621374 TI - [Characteristics of lipid metabolism in deep mine workers and the ways of its alimentary correction]. AB - Lipid and antioxidant state of clinically normal subjects working in deep mines was studied under natural conditions during one month. Disorders in lipid metabolism and intensified peroxidation were recorded in these subjects. A prophylactic ration has been recommended considering the food status, alimentary risk factors and extreme conditions of miners' labour. PMID- 1621375 TI - [Nutrition of boys aged 14-15 years from 2 regions of Moscow]. AB - Representative sampling of boys (n-577) aged 14-15 years was used to study their nutrition structure. The results obtained have evidenced the atherogenic character of nutrition due to insufficient consumption of vegetable oils, complex carbohydrates, excessive consumption of animal fats and sugar. These data can be used as the basis of nutrition correction for prevention of such risk factors of atherosclerosis as arterial hypertension, excessive body mass, dyslipoproteinemia. PMID- 1621376 TI - [Selenium intake by the population of Lithuania]. AB - The level of selenium was assayed in the blood and food products to study the providing of the Lithuanian population with this trace element. It was shown that imported wheat containing high levels of selenium played a significant role in providing with this trace element of the population of Lithuania, Estonia and Latvia where home-produced foods are deficient in selenium. The mean level of selenium in the blood serum of the Lithuanian population comprised 90 micrograms/l (96 micrograms/l was most frequent). Selenium consumption was 100 micrograms/man. PMID- 1621377 TI - [Vitamin B 12 metabolism and the status of sulfhydryl groups in protein-choline deficiency in rats. Effects of methyl- and adenosylcobalamins]. AB - The effect of low protein choline-deficient diet on total vitamin B12 content and individual cobalamin level in the blood serum and liver of rats was determined. Moreover the total and non-protein SH-group content and glutathione transferase activity in the liver of rats were studied. Total cobalamin content increased in the blood serum, but it did not change in the liver of rats fed choline-deficient low protein diet. Total and non-protein SH-group level as well as glutathione transferase activity in the liver decreased significantly. The causes of changes revealed are discussed. Methylcobalamin (but not adenosylcobalamin) administration normalized individual cobalamin level in the blood serum. Administration of both methylcobalamin and adenosyl-cobalamin resulted in total SH-group content restoration whereas non-protein SH-group level and glutathione transferase activity were restored only in methylcobalamin-treated rats. PMID- 1621378 TI - [Increasing the effectiveness of thiamine by its administration together with methionine and vitamin E]. AB - The influence of methionine and vitamin E, compounds intensifying thiol metabolism, on thiamine-phosphate level and thiamine-dependent dehydrogenase activity was studied in the liver of rats with varying thiamine providing: in case of its alimentary deficiency, and intensified thiamine consumption due to rat feeding with high-carbohydrate food. Methionine administration to vitamin B1 deficient rats led to a significant rise in thiamine-phosphate content and normalized alpha-ketoacid dehydrogenase acidity and non-protein SH-group level. Combined administration of thiamine with methionine and vitamin E increased the level of parameters studied. Methionine and vitamin E administered with thiamine intensified the regulatory action of thiamine on pyruvate dehydrogenase activity in the animals fed high-carbohydrate ration. PMID- 1621379 TI - [Effect of polyvitamin preparations on blood coagulation in experimental hypercoagulation]. AB - The influence of polyvitamin compounds on the course and outcome of experimental hypercoagulemia was studied. "Hendevitum", "Aerovitum" and "Undevitum" proved to be most effective in reducing negative results of thromboplastemia. "Glutamevitum" was insignificantly effective, while "Quadevitum" and "Complevitum" did not reduce animals' death rate after intravascular injection of thromboplastin in LD50. Positive effects of polyvitamin compounds might be associated with their capacity for stimulating anticoagulation potential, especially, in accelerated continuous intravascular blood coagulation. PMID- 1621380 TI - [Effect of carbohydrate structure on glucose utilization and biosynthesis of lipids, proteins and glucagon in rats]. AB - It was established that utilization of labelled glucose depended on food carbohydrate structure. Saccharose increased 1.5-fold the labelling of lipids in the liver and lowered insignificantly glycogen labelling. Similar quantity of invert sugar sharply reduced glycogen labelling. When starch was substituted for corn syrup lipid labelling increased two-fold, while glycogen labelling decreased down to 26% of the control level. Lipid/glycogen labelling ratio in saccharose feeding was 2, in invert sugar--4, in corn syrup--17. PMID- 1621381 TI - [Hydrolysis and absorption of lysozyme in the small intestine]. AB - Preparations of chicken small intestine were used in the experiment in vitro simulating processes of membranous digestion (inverted intestinal segments) and absorption (inverted intestinal myasis). It was established that lysozyme was hydrolyzed on the internal mucosa surface regardless of its concentration in the gastro-intestinal tract, and only insignificant quantity of lysozyme (0.027%) penetrates the intestinal wall. The method of lysozyme determination through its action on the cellular wall of Micrococcus lisodeicticus, and highly efficient liquid chromatography were used to study the transport process. The data presented have evidenced that lysozyme is well hydrolyzed under the action of intestinal peptide hydrolyses, and only insignificant amounts of non-splitted lysozyme can penetrate the blood. PMID- 1621382 TI - [Stochastic component of the effect of food, its nutritive value and the structure of nutrition of the population]. PMID- 1621384 TI - [Chemical composition of a protein concentrate from Saccharomyces and its effect on immunologic response]. AB - The content of the main nutrients, as well as amino-acid, fatty-acid and mineral composition of a protein concentrate prepared from yeast-Saccharomyces grown in molasses were studied. It was found that the product contained a significant amount of protein, all essential amino acids, insignificant quantity of lipids in which saturated fatty acids prevailed. The concentrate ash was rich in calcium, phosphorus, magnesium, silicon, iron and other elements. The protein product included into experimental rations during a month produced no significant effect on the B-system immunity and did not induce sensitization. PMID- 1621383 TI - [Effect of a new sweetening agent from Stevia rebaudiana on animals]. AB - Animals received saccharol adequate (by sweetness) to sugar, and in 10- and 50 fold increased amounts. The data of chronic 10-month experiments studied in the time course after 2, 5, 10 months have permitted a conclusion that saccharol included into the ration during long periods, does not produce a significant effect on the parameters of metabolic processes and morphological picture of the internal organs in test animals. Saccharol in 50-fold increased amounts inhibits the activity of oxidative phosphorylation in the hepatic tissue of rats. PMID- 1621385 TI - [Vitamin C stability in vitamin-fortified syrups]. AB - Factors influencing ascorbic acid stability in syrups were studied. It has been found that the vitamin stability depends on its concentration and the syrup composition. It is shown that vitamin C stability can be increased in some syrups by substitution of ascorbic acid for sodium ascorbinate. PMID- 1621386 TI - [Determining the level of riboflavin in food products by using riboflavin-binding apoprotein]. PMID- 1621387 TI - [Production technology and the glycemic index of bread]. PMID- 1621388 TI - [Reply to a reader's letter "Salt as a cause of various diseases"]. PMID- 1621389 TI - [Reply to a reader's letter "Preventive" salt]. PMID- 1621390 TI - [Effect of the LDL-/HDL-cholesterol quotient on progression and regression of arteriosclerotic lesions. An analysis of controlled angiographic intervention studies]. AB - The importance of hypercholesterolemia for the development of atherosclerotic lesions is undebatable. It is less evident, however, whether the progression of established lesions can be influenced by modifying lipid levels. The review of seven controlled angiographic intervention trials shows that different criteria are used to define progression of lesions. The relation of progression to regression (progression/regression ratio), however, is a useful marker for the activity of coronary artery disease. Patients with familial hypercholesterolemia have a progression/regression ratio of between 3 and 7. There is a consistent relationship between the progression/regression ratio and the LDL-/HDL cholesterol ratio in both control and intervention groups in these trials. Groups with a LDL-/HDL-cholesterol ratio of 5 have six times more progression than regression. If the LDL-/HDL-cholesterol ratio is less than 2.5 regression occurs more often than progression (i.e. progression/regression ratio less than 1). Thus, in the management of hyperlipidemic patients a LDL-/HDL-cholesterol ratio of less than 2.5 should be achieved if regression of atherosclerotic lesions is desired. PMID- 1621391 TI - [Characterization of LDL receptors in mononuclear cells of healthy probands and patients with familial hypercholesterolemia]. AB - Temperature-dependence, time-course, competition studies and saturation kinetics of the binding of either 123I-LDL or 111In-LDL to peripheral blood mononuclear cells (lymphocytes and monocytes) were determined in normolipemic controls and heterozygous familial hypercholesterolemia (FH) patients. Radioligand binding studies with 123I-LDL and 111In-LDL revealed similar binding characteristics. The maximal binding capacity was significantly reduced in FH patients (p less than 0.01) whereas the binding equilibrium dissociation constant was virtually unchanged as compared to healthy controls. PMID- 1621392 TI - The technique of taking brush biopsies of the nasal mucosa for electron microscopy. AB - Patients suffering from symptoms suggestive of a disorder of mucociliary clearance should be subjected to electron microscopic examination of the ciliated respiratory epithelium. Provided that all crucial points regarding technique and storage are adhered to, brush biopsy of the nasal mucosa is a reliable method facilitating the electron microscopical diagnosis of primary disorders of the ciliated epithelium. PMID- 1621393 TI - Diagnosis of tuberculous meningitis by detection of tuberculostearic acid in cerebrospinal fluid. AB - Tuberculous meningitis still poses a major diagnostic problem. Recently, several new techniques for rapid diagnosis of tuberculous meningitis have been developed. One of these newer techniques is the detection of mycobacterial fatty acids, using gas chromatography--mass spectroscopy. In this study we evaluated the sensitivity and specificity of this recently reported method in a blind trial. The sensitivity was found to be 100%, specificity only 91%. The number of false positive results limits the value of this test in the primary diagnosis of tuberculous meningitis. Nonetheless, we consider this method to be a valuable tool for establishing the diagnosis in culture-negative patients presenting with signs and symptoms suggestive of tuberculous meningitis. PMID- 1621395 TI - [Comment on the review article: Brosch, R., Buchrieser, C., Sixl, W., Rocourt, J.: 10 years food transmitted listeriosis--an evaluation]. PMID- 1621394 TI - [Polyglandular type I autoimmune syndrome]. AB - Two HLA-identical sisters have developed the full picture of type I polyglandular autoimmune syndrome over a period of 12 years. Both girls have hypoparathyroidism and Addison's disease. One of them additionally developed diabetes mellitus, hypergonadotropic hypogonadism and hypothyroidism. Autoantibodies to the adrenal, parathyroid and thyroid glands are present in both patients, as well as antinuclear antibodies. HLA associations have been described recently for the type I polyglandular autoimmune syndrome, but this could not be confirmed in the present two cases. Although we assume that the same genetic defect is present in both girls, additional factors to the genetic disposition are important for the clinical expression of the disease. The linkage of the disease-causing gene with the HLA region is not very close. PMID- 1621396 TI - [New, in Austria registered specialty drugs. Glucobay (acarbose)]. PMID- 1621397 TI - [Modern and general practice-oriented lipid and lipoprotein diagnosis]. PMID- 1621398 TI - [The cardiovascular effects of fish oil]. PMID- 1621399 TI - [Disappointments and hopes in tumor therapy with biological response modifiers]. PMID- 1621400 TI - [Modern wound dressings. 1: Alginates]. PMID- 1621401 TI - [The panorama of illnesses in advanced age. On the possibilities and reality of therapy]. PMID- 1621402 TI - [The historical medical instrument collection in the Kaiserin Friedrich House in Berlin (1907-1947). On the connection between medical education and the history of instruments in medicine in Germany in the 1st half of the 20th century]. PMID- 1621403 TI - [Sudden cardiac death--possibilities and limits of drug therapy]. AB - Sudden cardiac death is a challenge for primary prevention efforts, the rescue system, and the prophylactic antiarrhythmic medical therapy. A prerequisite for the successful prevention is insight into the pathophysiologic interaction of the arrhythmogenic substrate, the ischemic events, the autonomous nervous system, ventricular premature beats, left-ventricular function, etc. Latest results of prophylactic antiarrhythmic therapy indicate that the benefit under a specific antiarrhythmic treatment depends on the ratio of antiarrhythmic to proarrhythmic effects and the prevalence of sudden cardiac death in a given population. In diseased hearts with ventricular tachycardia or ventricular fibrillation the chance of sudden cardiac death is high, therefore, antiarrhythmic therapy is indicated and should be controlled by programmed stimulation. In patients with a low likelihood of sudden cardiac death after myocardial infarction, beta receptor blockers should be given; in certain higher risk patients (non-sustained ventricular tachycardia, reduced left-ventricular function) class-III antiarrhythmic agents are recommended. In hypertrophic cardiomyopathy (less in dilative cardiomyopathy) a beneficial effect of amiodarone becomes apparent in subgroups with high risk. Treatment of symptomatic ventricular premature beats remains empiric; in case of no or minimal structural heart disease, the arrhythmogenic potential is low. For the management of recurrent ventricular tachycardia new concepts are proposed that include antiarrhythmic agents and magnesium. PMID- 1621404 TI - [Sudden cardiac death: possibilities of interventional therapy]. AB - There is, at present, no method to prevent sudden cardiac death. However, in patients with documented high risk the implantable automatic cardioverter defibrillator is the only reliable alternative. However, the electrical discharges of high energy may cause discomfort and pain. Antitachycardia pacing is effective for most episodes of ventricular tachycardia and can effectively reduce the number of electrical shocks to be delivered. PMID- 1621405 TI - [Catheter ablation of septal accessory conduction pathways with high frequency electric current]. AB - In 58 symptomatic patients with septal accessory atrioventricular pathways, attempts at catheter ablation of the pathway were made using 500-kHz radiofrequency current. The methodological approach (introduction and final positioning of the ablation catheter) was dependent on the anatomical site of the accessory pathway. Right anteroseptal pathways were accessed via a jugular venous route, whereas a femoral venous route was used for right mid- and posteroseptal pathways. In these pathways, ablation was attempted from an atrial catheter position. Left posteroseptal pathways were located via mapping of the coronary sinus and were ablated either from the left ventricle or (in 3 cases) from the vena cordis media. Utilizing a deflectable catheter with a 4-mm tip electrode, ablation attempts were successful in 54 patients (93%) with a median of 12 radiofrequency current pulses of an average 24.9 W of power and 23.2 s length. The mean duration of the sessions was 4.6 h. Impairment of physiological conduction (first-degree AV block) was observed in 1 patient; complete heart block was never induced. Recurrences after initially successful ablation necessitated a repeat session in 2 patients. One patient died 3 days after successful ablation of a posteroseptal accessory pathway. Septal accessory pathways may be ablated using radiofrequency current with an efficacy and safety comparable to free-wall accessory pathways and with good preservation of physiological AV node-His bundle conduction. PMID- 1621406 TI - [Long-term follow-up of patients after interruption of the atrioventricular conduction by electrode catheter and DC shock: experiences with 100 patients]. AB - Long-term follow-up (44 +/- 21 months) was studied in 100 patients (pts) (mean age 56 +/- 12 years) who underwent direct current ablation because of drug resistant supraventricular arrhythmias. In 85 pts (85%) complete atrioventricular (AV) block was initially achieved. During the follow-up period, AV conduction resumed in 15 pts (15%). Thirteen pts underwent another ablation session and complete AV block was achieved in 11/13 pts (85%). After catheter ablation complete AV-block was achieved in 96 pts and the remaining four pts had second degree AV-block. Complications like pericardial effusion, arterial hypotension or ventricular arrhythmias occurred in 18 pts. Total mortality was 13% (13 pts): one patient died suddenly, and seven pts died from cardiac causes (heart failure in six pts, reinfarction in one patient). Transcatheter direct-current ablation is an effective method to interrupt AV conduction and to treat patients with drug resistant supraventricular arrhythmias. Although there is a small risk of severe complications, this procedure should be reserved for pts with supraventricular arrhythmias who do not respond to conventional drug treatment. PMID- 1621407 TI - [Additive effects of milrinone and dobutamine in severe heart failure]. AB - The hemodynamic effects of dobutamine, milrinone, and a combination of both drugs were compared intra-individually in 14 patients with severe heart failure (NYHA III: n = 9; NYHA IV: n = 5). Dobutamine (maximum dose: 9 micrograms/kg/min) and milrinone (0.5 micrograms/kg/min) each induced a comparable increase in stroke volume index (21 to 29 resp. 21 to 30 ml/m2; mean values; p less than 0.001) and reduction in pulmonary capillary wedge pressure (29 to 22 resp. 28 to 21 mm Hg; p less than 0.001), as well as in systemic (1846 to 1218 resp. 1858 to 1276 dyn s/cm5; p less than 0.001) and pulmonary vascular (301 to 195 resp. 293 to 216 dyn s/cm5; p less than 0.001) resistances. The heart rate rose significantly after dobutamine (92 to 107 min-1; p less than 0.05), but did not change after milrinone (94 to 95 min-1; ns). Neither drug had a significant effect on systemic arterial pressures. The combination of milrinone and dobutamine induced a further significant rise in stroke volume index (37 ml/m2; p less than 0.01) when compared to either drug alone. The combination also caused an additional fall in pulmonary capillary wedge pressure (14 mm Hg; p less than 0.01), as well as in systemic (799 dyn s/cm5; p less than 0.001) and pulmonary (133 dyn s/cm5; p less than 0.001) vascular resistances. When compared to dobutamine alone, the combined therapy did not significantly change the heart rate and systemic arterial pressures. The combined administration of a beta-adrenergic agonist and a phosphodiesterase inhibitor induces beneficial hemodynamic effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621408 TI - Short-term reproducibility of gas exchange measurements during bicycle exercise in patients with mild to moderate congestive heart failure. AB - A series of 45 patients with congestive heart failure due to coronary disease had semisupine bicycle exercise tests (ramp protocol, 10 W/min) on two occasions separated by 3 to 7 days in order to determine the short-term reproducibility of gas exchange measurements during symptom-limited exercise. The percentage difference (PD) between each pair of measurements (m1, m2; PD = 100%.(m2-m1): m1) were calculated. The mean PD values (+/- 1 sigma) and the single determination standard deviations (SDSD) for exercise tolerance (ET, W), peak heart rate (pHR, 1/min), peak oxygen uptake (pVO2, ml/min/kg), peak carbon dioxide output (pVCO2, ml/min/kg), and peak minute ventilation (pVE, l/min) were as follows: [table: see text] No patient reached a plateau of oxygen uptake during the last portion of the ramp exercise test. Thus, pVO2 is not an objective endpoint. The single determination standard deviations show that exercise tolerance and peak oxygen uptake do not differ as to their reproducibility. The absolute values of PD were not a function of exercise tolerance for any of the parameters studied. The PD values for ET and pVO2 were normally distributed. The data suggest that a change in ET and pVO2 must exceed 27% and 28% between two sequential studies in an individual patient in order to be significant at the 5% level, respectively. For the one-tailed test situation, the changes in ET or pVO2 must be greater than 23% in order to be significant. PMID- 1621409 TI - [Peri-graft reaction. A complication after implantation of a prosthesis shunt in children with congenital cyanotic heart defects]. AB - Two different clinical manifestations of perigraft-reactions complicating the implantation of prosthetic aortopulmonary shunts in children with cyanotic congenital heart disease are described and discussed. The incidence of this complication in the past 5 years in our own patients was 3%. The appearance of a localized mass on the chest film surrounding the prosthesis requires the exclusion of a hematoma, aneurysm or inflammation. In the case of a massive serous pleural effusion examination of the ingredients leads to diagnosis. Concerning our own patients the fluid is identical with serum; the leakage through the prosthesis can therefore be called plasmapheresis. The claimed pathogenetic causes are discussed intensively, including a chylothorax promoting this complication in the second case. Local variations in porosity and structure of the implanted prosthesis may play a critical role in the pathogenesis of perigraft-reaction, as indicated by both our reported cases. In the event of unsuccessful observation of a localized perigraft seroma or of unsuccessful chest drainage of a massive pleural serous effusion, graft replacement and placement of a different graft material are found to have the best results. PMID- 1621410 TI - [Contrast media in cardiology. Report of a randomized, double-blind multicenter comparative study of the side effects of ionic and non-ionic roentgen contrast media]. PMID- 1621411 TI - Immunization in the UK: policy review and future economic options. AB - Vaccination is one of the most effective health promotion activities, but specific targets have been difficult and costly to achieve, and have frequently fallen short of the desired aims, leaving some vulnerable groups unprotected. Policy in the UK has differed for the childhood diseases and in some cases, for example diphtheria and poliomyelitis, has been successful in almost eliminating the disease. In other cases, such as that of pertussis, there has been public opposition, and for other diseases, for example, measles, sufficient numbers of the susceptible population have only recently been reached. Although the World Health Organization target of 90% uptake for the childhood diseases has been reached for all except pertussis, the figures conceal lower uptake rates in some areas, particularly the inner cities. The introduction of target payments to general practitioners appears to have had some effect in increasing uptake rates, particularly in some inner city areas, although the change in immunization schedules may also have had an impact. Target payments fail to take account of the difficulties faced by inner city GPs and, in effect, favour those who need to make least effort, since, in some areas, high uptake rates may already have been achieved before targets were introduced. It is suggested that there is a case for special local development programmes in inner city areas which will provide help with improving record keeping and recall systems for immunization. An alternative policy, which might be more difficult to implement, would be to have targets which could be set at different levels in different areas so that uptake rates could be progressively improved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621412 TI - Clinical and bacteriological studies of El Tor cholera after ingestion of known inocula in Thai volunteers. AB - Twenty-six healthy adult Thai volunteers were recruited for clinical and bacteriological studies of cholera induced by oral inoculation with Vibrio cholerae El Tor Inaba strain N16961. Vibrio dosages of 0.3 x 10(4), 1.6 x 10(5) and 1.9 x 10(6) c.f.u. were given to three groups of five volunteers, and 2.0 x 10(7) c.f.u. to 11 volunteers. Diarrhoeal attack rates correlated positively with the size of the inocula (p less than 0.01). It was estimated that a diarrhoeal attack rate of 90% (ED90) would be achievable by inoculation of 1.3 x 10(7) c.f.u. of the organisms. There were no significant differences between the groups in the latent period to positive stool culture, maximum vibrio count per gram of stool and duration of stool positivity. The ED90 of V. cholerae obtained may be used as a challenge dose in subsequent studies on protective efficacy of cholera vaccines in Thai adult volunteers. PMID- 1621413 TI - Local and systemic influenza haemagglutinin-specific antibody responses following aerosol and subcutaneous administration of inactivated split influenza vaccine. AB - An easily administered and safe vaccine is required to produce the herd immunity necessary to control influenza epidemics worldwide. A commercial quadrivalent inactivated split influenza vaccine was administered intranasally in aerosol form to a group of 46 volunteers; other groups were given the same vaccine subcutaneously and saline intranasally. The results show that mucosal stimulation via intranasal vaccination resulted in a marked increase in local HA-specific IgA antibodies, and that this stimulation was necessary for serum HA-specific IgA responses. Serum HA-specific IgA antibody levels can be used as indicators of local antigenic stimulation, providing a method for evaluating potency and antigenicity in humans of intranasal influenza vaccine. This vaccination route shows much promise for the future. PMID- 1621414 TI - Immunization of pigs against Actinobacillus pleuropneumoniae with two recombinant protein preparations. AB - Two Actinobacillus pleuropneumoniae serotype 7 antigens were expressed in Escherichia coli and tested for their protective efficacy in an experimental pig model. The antigens used were a fusion protein containing the carboxy-terminal 70% of the +/- 103 kDa cytolysin and a full length 60 kDa protein which has been shown previously to bind transferrin. Pigs were immunized twice with 25 micrograms of either or both preparations. All pigs developed a strong humoral immune response comparable to that induced by infection. Upon challenge with an A. pleuropneumoniae serotype 7 strain, all immunized groups were less affected by the disease and showed significantly lower mortality than the controls (p less than 0.1). Pigs receiving both antigens had a tendency to recover faster than the controls or animals which were vaccinated with only one antigen. Protection was serotype-specific since no cross-protection was detected following challenge with an A. pleuropneumoniae serotype 1 strain. A dose-response experiment using the single antigens at 200, 50 or 12.5 micrograms per dose showed no difference in protection among the groups. PMID- 1621415 TI - Recent observations regarding the pathogenesis of recurrent respiratory syncytial virus infections: implications for vaccine development. AB - Respiratory syncytial virus (RSV) and influenza virus are common pathogens for all age groups. Currently licensed influenza virus vaccines generally provide protection from clinically detectable disease caused by antigenically matched challenging viruses. In contrast, vaccine development for RSV has been hampered by the inability of candidate vaccines to induce protective immunity to naturally occurring infection. The precise mechanism(s) responsible for the RSV vaccine failures have not been determined. We raise the possibility that infection by RSV is associated with attenuation of both proliferative and non-proliferative RSV specific responses by human mononuclear leucocytes that results in the suppression or delay of host anamnestic defences, allowing development of recurrent clinical illness despite pre-existing immunity. PMID- 1621416 TI - Potential pathogenicity for rodents of vaccines intended for oral vaccination against rabies: a comparison. AB - Different oral vaccines intended to control fox rabies were administered to 271 wild rodents. Vaccines were administered orally or by the mucosal route to four different European species belonging to the genera Apodemus, Arvicola, Clethrionomys and Microtus. These rodents are likely to consume baits and to have contact with the vaccine. Two genetically engineered vaccines were tested: SAG1 (an avirulent mutant of the rabies virus) and V-RG (vaccinia recombinant virus expressing the rabies glycoprotein gene). Both were found to be completely innocuous when administered orally or by the mucosal route. The residual pathogenicity of conventional modified live vaccines derived from the SAD strain was confirmed. PMID- 1621417 TI - Development of a live cell culture camelpox vaccine. AB - A Saudi isolate of camel orthopoxvirus was serially propagated on monolayers of camel kidney cell cultures. The attenuation of the 78th passage was tested in two susceptible camels. Two other susceptible camels were inoculated with vaccinia virus four times propagated in camel kidney cell cultures. The four inoculated camels showed no postinoculation clinical symptoms and formed neutralizing antibodies against both the camel orthopox and vaccinia viruses. No postchallenge clinical symptoms were observed in these four camels, while two non-inoculated contact control camels showed typical symptoms of generalized camelpox. These results indicated the safety and potency of the 78th passage of the Saudi isolate of camel orthopoxvirus (designated Jouf-78) to be used for production of live attenuated cell culture camelpox vaccine. The field testing of the vaccine was carried out on two farms using at least 10(3) TCID50 as a recommended field dose. None of the inoculated camels showed any postvaccination reaction and the serological tests showed seroconversion of many vaccinated field camels. The relationship between camel orthopoxvirus and vaccinia virus as well as the advantages of the live attenuated camelpox vaccine are discussed. PMID- 1621418 TI - Antibody responses stimulated in rabbits, guinea-pigs and mice by recombinant and synthetic portions of a 75 kDa malarial merozoite protein. AB - The 75 kDa heat-shock-related protein (p75) of Plasmodium falciparum is an abundant, highly conserved, merozoite surface protein. A bacterial clone, C7, produces a polypeptide (C7Ag) of approximately 30 kDa representing the C-terminal 40% of p75. In several species of animals, the C7Ag stimulated high titre IgG antibodies which cross-react with p75. Two major portions of the C7Ag, theoretically predicted to have strong secondary structural preferences, were modelled with four synthetic peptides. An alpha-helical, hydrophilic region, modelled with a 28-mer, proved a poor immunogen in guinea-pigs and several strains of inbred mice, even though it had been a strong immunogen in rabbits. A disulphide-bonded region of the C7Ag was modelled with three peptides of increasing length, namely 49-, 64- and 76-amino acid residues. In general, the order of immunogenicity was 49 less than 64 less than 76-mer. Antibodies to the 76-mer and the 64-mer reacted strongly with the native parasite protein. The data also suggested that the 76-mer was a good model for the region of the molecule it was made to represent. PMID- 1621419 TI - Changes and challenges in health insurance. PMID- 1621420 TI - Dental model storage--a new and efficient system. PMID- 1621421 TI - Mouthguards, nightguards, palliatives and collaboration. PMID- 1621422 TI - Radiation protection & regulations. Subject: reducing exposure with rare earth intensifying screens. PMID- 1621423 TI - Recurrent aphthous ulcerations. PMID- 1621424 TI - Vital tooth bleaching--home use review and evaluation. PMID- 1621425 TI - Direct and indirect veneers. PMID- 1621426 TI - Composite resin inlays. PMID- 1621427 TI - Quality in the service of patients: the paradigm of the 90s and beyond. PMID- 1621428 TI - Clinical information content of transcutaneous oxymetry (tcpO2) in peripheral arterial occlusive disease (a review of the methodological and clinical literature with a special reference to critical limb ischaemia). AB - About 160 publications (1978-1992) dealing either directly or indirectly with transcutaneous oxygen partial pressure measurements (tcpO2) in peripheral arterial occlusive disease (PAOD) are reviewed. Thereby, various clinical applications and results are related to the theory and methodology of the tcpO2 technique. In PAOD patients, the tcpO2 reflects local hyperemic skin blood supply. The clinically relevant intersection of the tcpO2-flow hyperbola is of considerably non-linear shape and partially insensitive to flow. In view of macrocirculatory pathology, tcpO2 values depend particularly on PAOD staging, hemodynamic compensation, and calf artery patency. Pathophysiological and pharmacological microcirculatory effects, however, cannot be read unequivocally from corresponding tcpO2 responses due to the heat-induced local vasoparalysis. In daily practice, the tcpO2 does not provide substantial information in patients with asymptomatic obstructions (Fontaine stage I) or intermittent claudication (stage II) but is of clinical impact in limbs with rest pain and skin lesions (stages III and IV). In such a complicated PAOD, diagnostic and prognostic capabilities can be essentially improved by provocational manoeuvres which narrow the flow-insensitive range. A critical limb ischaemia may be assumed if supine and dependent foot tcpO2 values exceed neither 10 mmHg nor 45 mmHg, respectively. PMID- 1621429 TI - [Expression of induced atherosclerosis in the rabbit model]. AB - Atherosclerosis in rabbits was induced by administering a 2% cholesterol diet and additional endothelial denudation of the aorta and iliac artery as a model for vascular surgery. In addition, the serum cholesterol-, serum triglyceride-, and HDL-cholesterol values were examined. After 22 weeks the intima and most often the media showed atheromatosis and fibrosis, in most of the arteries with intimal necroses. All arteries developed marked to pronounced stenoses, calcium deposits were only observed in single cases. The intensity of the arterial lesions was found to be similar to the appearance of human atherosclerosis. PMID- 1621430 TI - Vasomotion in the leg skin of patients with chronic venous insufficiency. AB - The characteristics of vasomotor activity in patients with lipodermatosclerosis (LDS) were studied using Laser Doppler fluxmetry and frequency analysis. Laser Doppler flux in the skin was recorded in the goiter region in 17 patients with LDS due to venous disease and in 16 normal control subjects. The Laser Doppler signals were analysed to give mean levels of flux and the frequency and amplitude of vasomotion were found using a fast Fourier transform (FFT). The results show significantly greater basal flow (p less than .001), and vasomotor frequency (p less than .001) and amplitude (p less than .001) in venous disease. The altered vasomotor activity is not due simply to the increased flow in LDS since increasing the flow in normal skin using the vasodilator pilocarpine does not produce as noticeable a difference. PMID- 1621431 TI - Immunofluorescence studies of atrophie blanche with antibodies against fibrinogen, fibrin, plasminogen activator inhibitor, factor VIII-related antigen, and collagen type IV. AB - In and around ulcers complicating the chronic venous insufficiency syndrome and atrophie blanche a pericapillary cuff of fibrinoid material has been described. The aim of the present study was to find out whether pericapillary cuffs are present in atrophie blanche ulcerations, whether they consist of fibrinogen and/or fibrin in comparison to normal controls, and whether this cuff is composed of other components. Skin biopsies from ten patients adjacent to atrophie blanche ulcers, and from ten controls were taken. In all patients pericapillary cuffs consisting of fibrin were found. However, no fibrinogen was found in these cuffs. In the controls no cuffs were found. In this fibrin network factor VIII-related antigen and collagen type IV were also present. The finding of plasminogen activator inhibitor-I in the pericapillary cuff in several cases may indicate that breakdown of this fibrin cuff is impaired. The possible diffusion barrier caused by the pericapillary cuff together with the pattern of vascularization may be an important event in ulcer formation and impaired ulcer healing. PMID- 1621432 TI - Skin microcirculation and laser Doppler blood flow in patients supported by the Berlin heart biventricular assist device. AB - Microcirculatory forearm cutaneous blood flow was monitored continuously and non invasively by laser-doppler-flowmetry (LDF) in 10 patients treated with the Berlin Heart biventricular assist device (BVAD) system for end-stage heart failure (BVAD-pts). Ten normal human subjects served as controls (C). The cutaneous blood flow was measured before, during, and after external brachial artery occlusion to evaluate the postocclusive reactive hyperemia (PORH) as a standardized response. To examine micro-vasculatory responses to macro hemodynamic changes the cardiac output (CO) was decreased by reducing the BVAD pump rate by 20%. No significant differences in base-line LDF measurements were ascertained in the two groups. After sudden cuff pressure release (1 min later) a statistically significant (p less than 0.004) three- to fourfold blood flow increase (PORH) occurred in both groups. The period of the PORH response was altered in all BVAD-pts. The time to peak PORH values were significantly diminished (p less than 0.05) A markedly delayed return to base-line level occurred in the BVAD-pts. The 20% reduction in the BVAD-pump rate significantly decreased CO (p 0.05) and increased systemic vascular resistance (SVR) (p less than 0.01), whereas LDF levels remained unchanged. PMID- 1621433 TI - The value of arterial, venous and arteriovenous levels of lipid metabolism parameters in healthy individuals and patients with peripheral arterial occlusive disease (PAOD). AB - For a group of 28 patients with PAOD (mean age, SD 63.7 +/- 10.2 years) and 16 healthy subjects (61.7 +/- 11.9 years) we examined several lipid analytes in femoral arterial and venous blood. Compared with healthy controls, PAOD patients showed significantly lower HDL cholesterol levels (p less than 0.01) and significantly higher levels of triglycerides (p less than 0.01). In addition, a significant negative A-V difference in triglycerides (p less than 0.05) and a significant inverse association between arterial HDL cholesterol and A-V difference in triglycerides (r = -0.48; p less than 0.01) were present. Predominantly the last two unexpected findings are discussed in this study. PMID- 1621434 TI - IgG-anticardiolipin-antibodies are markers for cerebral and peripheral artery disease. AB - Anticardiolipin-antibodies are antibodies to phospholipids which were first detected in patients with arterial thrombosis and lupus erythematosus. In this prospective study, IgG- and IgM-anticardiolipin-antibodies were determined in patients with cerebral and/or peripheral artery disease but without autoimmune disorders. 123 randomly selected patients (88 males, 35 females; mean: 65 +/- 10, range: 41-85 years) were included and divided into four groups: 18 patients with isolated cerebrovascular disease (group A), 35 patients with peripheral artery disease only (group B), 35 patients suffering from cerebral and peripheral artery disease (group C) and 35 patients as controls (group D). In family history, cholesterol, blood sugar and prothrombin time the four patient groups did not differ significantly, whereas patients of group B and C were more often smokers than those in groups A and D. However, IgG-anticardiolipin-antibody-levels were significantly elevated in patients with cerebral and peripheral artery disease compared to controls (p less than 0.01). The highest values were seen in group C where patients suffered from cerebral and peripheral artery disease (n.s.). On the other hand, IgM-anticardiolipin-antibody-levels did not show any differences in the four groups. Furthermore, there was no correlation between vascular risk factors and/or laboratory findings with IgG- and IgM-antibody-levels. Thus, elevated IgG-anticardiolipin-antibodies appear to be independent markers for severe cerebral and peripheral artery disease and should be determined in patients at increased risk. PMID- 1621435 TI - Retinal duplex scanning in cerebrovascular disease and hypertension. AB - Using Doppler duplex scanning retinal flow velocity was evaluated in 100 patients with carotid plaques, in 40 with hypertension and in 200 normal subjects. The reproducibility of the test was good. Peak systolic velocity was 12.5 cm/s in normals and significantly lower in patients with carotid plaques (9.8 +/- 6) and in patients with hypertension (8.3 +/- 6). The end diastolic velocity was also lower in both groups of patients. The ratio between the systolic and diastolic component was 2.3 in normals. It was increased in cerebrovascular disease (3.5) and in hypertension (5.5) as a consequence of the decrease in the diastolic component. In conclusion duplex retinal flow velocity evaluation is easy and reproducible and may be possibly used to study retinal flow in patients with cerebrovascular disease and in hypertension. PMID- 1621436 TI - Evaluation of patients with thoracic aortic dissection by intraarterial digital subtraction angiography. AB - In 17 patients (mean age 60 years) a thoracic aortic dissection could be revealed by intraarterial digital subtraction angiography with exact delineatin of the proximal and distal extent. Furthermore a visualisation of the true and false lumen and hereby especially the blood flow and its direction in the false lumen could be made. The disclosure of the intimal flap could be seen in patients with flow in both channels, separating the true and the false lumen. In 4 patients the entry could be seen sharply as a hole, but not corresponding to the proximal extent. In 11 patients the entry was seen over a longer area and in 2 patients neither entry nor reentry could be seen. The most distal part of the intimal flap might correspond to the reentry. One anonymous artery, five renal arteries and one coeliac trunc were involved by the dissection. The exact anatomical and pathophysiological nature of the dissection made it possible to decide whether or not the patients should be operated upon and if so, what kind of operation should be chosen. PMID- 1621438 TI - [Results of vascular surgery treatment of vertebrobasilar insufficiency]. AB - A retrospective analysis of the data of 64 patients with vertebral-basilar insufficiency is presented who were operated between 1980 to 1919 in our institution. Surgery for vertebral-basilar insufficiency comprises only 5.2% of all 1422 supra-aortic reconstructions performed during this period. The leading symptom was vertigo which was present in 41%. Disturbances of vision occurred in 9.8%. 29 bypass procedures and 35 arterial transpositions were performed. A mean follow up of 5.1 years revealed a patency rate of 83.3% in bypass procedures, 92.8% in subclavian transpositions and 100% in vertebral artery transpositions. These good haemodynamic results correlated with marked improvement of the clinical symptoms in 80% of the patients. PMID- 1621439 TI - Deep venous thrombosis: results of thrombectomy versus medical therapy. Presented at the 5th European-American Symposium on Venous Diseases, Vienna, Austria, Nov. 7-11, 1990. AB - Between 1.1.1985 and 1.1.1988, 158 patients were referred because of acute deep venous thrombosis. They were 82 women (median age 48.5) and 76 men (median age 56.5). On admission, 4 patients had already a pulmonary embolism in 3 others embolism occurred during hospitalisation. The segment involved was the isolated iliac in 10, iliofemoral in 53, isolated femoral in 7, femorotibial in 47 and isolated tibial in 41 patients. Anticoagulation and compression therapy was undertaken in 102 and mortality was 21%. At follow-up 63% had at least 1 sign of venous insufficiency, in all 16% had no sequelae and were subjectively symptom free. Thrombolytic therapy was carried out in 25, mortality was 8%. At follow-up, 72% had at least one sign of venous insufficiency. Venous thrombectomy was performed in 31, combined in 4 with balloon dilatation of an iliac spur. Mortality was low with 3%, 58% had at least one sign of venous insufficiency at follow-up and 39% were subjectively symptom-free. Our results show that an objective assessment is insofar difficult because subjective and clinical results do not correlate; 51% with clinically verified post-therapeutic venous insufficiency had normal venous drainage in strain-gauge plethysmography, whilst 41% without subjective discomforts demonstrated an insufficient drainage. Our results show that a full restitution is seldom achieved, thrombectomy does not prevent chronic venous insufficiency. Best results were observed in isolated iliac thrombosis. We conclude that thrombectomy should be restricted to the phlegmasia caerulea dolens form of DVT, while floating thrombus and ascending thrombus extending into the vena cava should be treated with a cava filter or ligation. PMID- 1621437 TI - [Five years experience with infra-inguinal arterial reconstruction: a comparison of venous with PTFE bypass]. AB - Since January 1983 one surgeon of our team has performed 200 infrainguinal arterial reconstructions. Our patients had a mean age of 72 years and suffered from multiple concomitant diseases (coronary heart disease 35%, cerebro-vascular insufficiency 15%, hypertension 49% and diabetes mellitus 34%). The indication for arterial reconstruction was a chronic critical ischemia in every case. 154 autologous veins and 46 PTFE prosthesis had to be implanted. The former consisted in 64% in a femoropopliteal and in 35% femorodistal bypass graft; respective values of the latter group were 80% and 20%. The cumulative survival rates of two collectives were nearly identical. More than 50% of our patients died in the 4 years observation period. The life table patency rates differed statistically significant (p less than 0.001). The cumulative 5 year patency amounted to 85% in case of a vein graft and to 43% if a PTFE prosthesis was inserted. Extremely poor results were achieved in case of a PTFE prosthesis with a distal anastomosis to a single crural artery; just one out of 6 procedures was successful after two years. PMID- 1621440 TI - Medical edema protection--clinical benefit in patients with chronic deep vein incompetence. A placebo controlled double blind study. AB - In a randomized placebo controlled parallel double blind study on 40 patients suffering from venous edema in chronic deep vein incompetence, the edema-reducing effect of horse chestnut seed extract vs. placebo, being the main test variable, was demonstrated by hydroplethysmography to be statistically significant. In addition, measurements of leg volume under aggravated conditions (edema provocation) were conducted, which yielded the same results. Additional measurements of leg circumference tendentially confirm the demonstrated clinical efficacy of verum, as is true for phlebody-namometric measurements (pressure at rest, minimum pressure, replenishment time) as well. By measuring the leg volume before and after edema provocation, it could be shown that the clinical benefit for the patient is present in all everyday situations (in movement as well as on sitting or standing). Treatment with an edema protective agent of the horse chestnut seed extract type is thus a useful adjunct to compression therapy. The tested preparation were well tolerated. PMID- 1621442 TI - The effect of elastic compression on the venous tone in patients with varicose veins. AB - The long term effect of elastic compression, with an emphasis on the changes in venous wall elasticity, was studied in 10 limbs with varicose veins. By simultaneously measuring venous volume, using the air plethysmograph (APG), and venous pressure, while the venous outflow was occluded, the pressure/volume (P/V) relationship of the venous system of the leg could be studied and the elastic modulus calculated. These measurements were performed prior to the application of elastic stockings and 6 weeks later, one day after the stockings had been removed. Statistically significant improvements were noted in the APG parameters studied and in the P/V curve derived elastic modulus calculations. The limbs could be divided into two groups based on the response of the P/V curves to elastic stockings and the severity of disease. Those limbs with milder disease tended to shift their P/V curves downward and to the right after compression (giving them a more normal pattern). Limbs with more severe disease showed evidence of a similar pattern of improvement at low but not at high venous pressures. PMID- 1621441 TI - Elastic stockings in diabetic microangiopathy. Long-term clinical and microcirculatory evaluation. AB - One hundred and forty nine diabetics with microangiopathy were followed up for 4 years and studied by laser-Doppler flowmetry - measuring skin blood flux at rest [RF] and the venoarteriolar response [VAR]. Seventy four patients were advised to wear elastic stockings and 75 were kept as controls with the aim of evaluating the effects of stockings on the evolution of diabetic microangiopathy. After 4 years a significant deterioration was found in RF (increased) and VAR (decreased) in the untreated group in comparison with controls. Also 10 ulcerations developed in the untreated subjects (6.6% of limbs) in comparison with 3 ulcerations (2.02%) in the treated group. The difference was statistically significant. Therefore elastic stockings appear to be useful in diabetics with microangiopathy as they protect against the deterioration of the microcirculation and reduce the development of ulcerations. PMID- 1621443 TI - Venous function during late pregnancy, the effect of elastic compression hosiery. AB - Venous function was investigated in 29 women during late pregnancy before and after short term treatment with graduated compression hosiery. A significant improvement of venous emptying was found, combined with a subjective decrease of leg problems such as swelling, tiredness and pain. PMID- 1621444 TI - [Exercise for venous insufficiency 1992]. AB - A program of seven body exercises which was developed at our clinic in 1969, is presented in a new and adapted version. These exercises support the natural drainage function of the venous and lymphatic reflux system. The posture (elevated position of the pelvic area) and an adequate respiration during the exercises are of paramount importance. Exercises supporting the drainage function are only part of several components of the individually adapted therapy program. Within these limits they represent one of the most valuable measures, because they are carried out entirely by the patient himself. PMID- 1621445 TI - Present management of hepatic artery aneurysms. Symptomatic left hepatic artery aneurysm; right hepatic artery aneurysm with erosion into the gallbladder and simultaneous colocholecystic fistula--a report of two unusual cases and the current state of etiology, diagnosis, histology and treatment. AB - A left hepatic artery aneurysm has an incidence of 0.8% among the splanchnic artery aneurysms. 20% of splanchnic artery aneurysms are hepatic artery aneurysms. Atherosclerosis (32%) is the most prevalent etiology, followed by trauma (22%) and inflammatory lesions (10%). The average age is 40 (10-83) years, the male to female ratio 2:1. In 64-80% of cases rupture of the aneurysm is the first clinical manifestation. The mortality is then about 35%. The case of a 64 years old female with a symptomatic aneurysm of the left hepatic artery and the case of a 70 years old female, who underwent emergency laparotomy for acute colorectal hemorrhage, with a right hepatic artery aneurysm, which perforated into the gallbladder, with simultaneous colocholecystic fistula is reported and the etiology, histology, and present diagnostic and therapeutic management of hepatic artery aneurysms is discussed. PMID- 1621446 TI - [Acute ischemia of the lower extremity in an adolescent with Crohn disease]. AB - The authors report a case with a rare form of peripheral ischaemia. A 25-year-old man with Crohn's disease suffers from sudden ischaemia of his right leg. There is no evidence of entrapment of the popliteal artery, of arterial embolism or Buerger's disease. Thrombocytosis in combination with hypercoagulability as described previously in patients with Crohn's disease seems to be the most probable cause. - In this case percutaneous transluminal thrombectomy and thrombolysis were more successful than surgical thrombectomy using balloon catheters. PMID- 1621447 TI - [Schorsch Gaggo visits a continuing education event]. PMID- 1621448 TI - Aluminium determination in food matrices IUPAC check sample survey of analytical performance. AB - Aluminum has been determined by 24 laboratories in the context of a check sample survey. Samples studied were two duplicate diets, one of which was spiked with 15.87 mg Al/kg, and two blind duplicate milk powders. Target values for the duplicate diets were 11.80 and 27.90 mg Al/kg, respectively, and 15.65 mg Al/kg for the milk powders. Participants were requested to make only single determinations per sample. A two-step approach was used to assess the raw data. In the first step, those data were excluded that were outside a +/- 50% range of the duplicate diet spike and the target value for milk powder. Likewise, only one single data set per participant was accepted and results were ruled out stemming from procedures that have a detection limit of greater than 5 mg Al/kg. The remaining data were evaluated both statistically and in the context of the method performance parameters available. Best scores for aluminium were from laboratories applying wet-pressurized digestion in combination with electrothermal atomic absorption spectrometry. Results for laboratories applying dry-ashing for sample decomposition were unreliable. The overall performance for aluminium is very disappointing given the relatively high aluminium levels of the samples studied. Out of 24 laboratories 11 have one or more major problems with their aluminium determination. They should dramatically improve or replace their methodology for this element. PMID- 1621449 TI - Action of gamma-irradiated patulin on Saccharomyces cerevisiae. AB - The action of gamma-irradiated patulin on Saccharomyces cerevisiae LOCK 2144 in liquid culture was studied. Patulin irradiated in an aqueous solution with doses ranging over 0.34-1.36 kGy inhibited the yeast growth in a proportion to the concentration of undestroyed toxin. Patulin disappearance in the growth medium occurred between 12-72 h of incubation at 30 degrees C. The patulin content did not essentially change in the period of log phase of yeast growth which is accompanied by rapid glucose uptake. PMID- 1621450 TI - [Determination of vitamin D in food using high performance liquid chromatography (HPLC). Results of collaborating studies of the working group "Vitamin Analysis" according to section 35 of the German Food Act]. AB - A standardized method to determine the vitamin D content of food by means of HPLC is described. After the test material was homogenized and saponified with ethanolic aqueous potassium hydroxide solution, vitamin D was extracted using n hexane. Using HPLC on a silica gel column, the fraction containing vitamin D is separated from the nonsaponifiable residue. After the fraction was reduced, the residue was dissolved in methanol and the vitamin D content determined after HPLC separation on an RP-C18 column. For evaluation, either a conventional external standard method using laboratory and matrix specific recovery rates as correction factors, or an internal standard method using vitamin D2, and D3, respectively as internal standards were employed. The method was developed and standardized by the working group "Vitamin Analysis" in accordance with section 35 LMBG (German Food Act). Repeatability and comparability of the results were checked in collaborative studies (14 laboratories) in milk powder and gruel that had been enriched with vitamin D3. Applicability of the method to other food (eggs, milk, fish, margarine) was checked separately. The statistical evaluation of the results of the collaborative studies has shown that the method is reliable enough to be included into the "Amtliche Sammlung" (official collection of analytical methods) according to section 35 LMBG. The present method may be used to determine the content of vitamin D2 and D3 in natural and vitaminized food. It is specific for the vitamins D2 and D3 released during saponification of food, but does not allow separate determination of the pre-vitamins D already present in the sample. PMID- 1621451 TI - Baking stability of acesulfame K. AB - The stability of acesulfame K during baking was investigated at different baking temperatures and baking times. The contents of acesulfame K in baked and unbaked doughs were determined by HPLC. The recovery rate of acesulfame K was independent of the baking conditions chosen and correlated with the recovery rate of acesulfame K in the unbaked doughs. As the stability of acesulfame K cannot only be affected by baking temperature and baking time but also by pH value and moisture content of the baked goods, additional stability investigations were performed with acidic fillings and apple pie. Even under these extreme baking conditions no decomposition of acesulfame K could be detected. PMID- 1621452 TI - [Anti-phospholipid antibodies in gynecology and obstetrics]. AB - Anti-phospholipid-antibodies are connected with many diseases. In gynecology and obstetrics they are related to habitual abortion, preeclampsia, intrauterine retardiation and thrombembolic events. Pathogenetic conceptions, the diagnosis, problems in contraceptions, pregnancies and puerperium are explained. Their search and an individual trial of therapy should be done in spite of unknown mechanism of effectiveness. PMID- 1621453 TI - [Changes in the blood coagulation and fibrinolysis system in the course of normal pregnancy]. AB - In the present study we investigated several factors of hemostasis and fibrinolysis during the normal pregnancy in 52 women. Whereas the Thrombin-Time did not show any change, the increase of the Hepato-Quick and the decrease of the Partial Thromboplastin-Time was significant. During pregnancy we observed a significant increase of the activity of fibrinogen, factor XII and prekallikrein as well as of the von-Willebrand-factor-antigen (VIIIR:Ag). The activity of factor II and X remained constantly. The increased activity of factors of hemostasis was accompanied by an increase of activity and concentration of antithrombin-III. In contrast to the activity of the hemostatic system we could not find any significant alteration of the fibrinolytic system. The cause must be searched in the observed increase of plasminogen-activator-inhibitor (PAI)--likly in combination with a decrease of the tissue-type plasminogen activator (t-PA). Our data indicate, that the highest risk for thrombosis already might exist in week 24 of pregnancy, because a distinct increase of hemostatic activity is combined with a nearly unchanged fibrinolytic activity. PMID- 1621454 TI - [Choroid plexus cysts in the 2d trimester--an indication for trisomy 18]. AB - The application of high resolution ultrasound in the prenatal diagnosis enables a detailed differentation of the intracerebral structures in the fetus. In a period of 16 months (Jan. 1990-June 1991) we diagnosed at the "Center for prenatal diagnosis and therapy" at the Charite's Hospital in 14 fetuses among 1800 investigated plexus chorioideus cysts. A rapid karyotyping after cordocentesis was performed in 11 cases. In 3 of them a trisomy 18 could be detected. In one fetus having a normal karyotype we could find besides the cysts multiple structural anomalies. In these 4 cases the termination of pregnancy was performed. In the other 10 pregnancies we could observe a spontaneous regression of the plexus cysts. These results suggest that the prenatal diagnosis of plexus chorioideus cysts is a indication for cytogenetic evaluation in order to detect a trisomy 18. PMID- 1621455 TI - [Fetal teratoma--diagnosis and management]. AB - Fetal and neonatal teratoma is rare, but it is the most common tumor of the fetus and meonate. We report seven cases with fetal sacrococcygeal teratoma and two cases with craniocervical teratoma. The diagnosis, further management of pregnancy and birth are described and compared with recent literature. While craniocervical teratoma is associated with very poor prognosis, there are sacrococcygeal teratoma with good survival rate and postoperative good functional results. Very important is prolongation of pregnancy near to term. PMID- 1621456 TI - [Type and incidence of cytogenetic abnormalities in unfertilized or uncleaved human oocytes within the scope of in vitro fertilization]. AB - Human oocytes remaining unfertilized or uncleaved during in vitro fertilization (IVF) yield valuable information on the kind and frequency of numerical and structural chromosome aberrations after their fixation. This enables us to assess the maternal contribution to perturbations in the course of fertilization and early embryonic development. Therefore, 566 unfertilized or uncleaved oocytes from our IVF programme were processed for cytogenetic examination. 223 gametes were not analyzable. 260 oocytes were completely karyotyped and chromosome counts could be established for 83 cells. 243 eggs had the normal haploid chromosome complement whereas 100 cells (29.2%) were abnormal. In detail, we found the following aberrations: hypohaploidy = 10.2%, hyperhaploidy = 4.7%, diploidy = 9.0%, tetraploidy = 1.2%, structural anomalies = 2.6%, prematurely condensed sperm chromosomes = 3.2%. Six cells had to be considered in two of these categories. Our results and comparisons with other publications imply that the total rate of anomaies in human oocytes from stimulated cycles amounts to 20 to 30%. This high frequency might be one of the limiting factors for the success rate of IVF. PMID- 1621457 TI - [Histomorphology of pelvic floor muscles in women with urinary incontinence]. AB - Success of urinary incontinence surgery so far depended primarily on the intensity and quality of preoperative diagnosis, the resulting choice of techniques, suture material, and the surgeon's skills. The role played by tissue available from the patient herself, however, had not been adequately considered, although such an assessment would have been of major relevance to all methods using autogenic tissue. Preliminary histological-histochemical and morphometric investigations of pubococcygeal muscles of ten patients revealed unambiguous right-left differences with regard to muscle quality and fibre typing, mean cross section area of muscle fibres, and connective tissue response up to degeneration and also concerning replacement of striated muscles by smooth muscles. Further studies into collagen metabolism are likely to enable more reliable prognosis of operations for urinary incontinence. PMID- 1621458 TI - [Treatment of stress incontinence]. AB - This is an introducing survey at the symposium "New techniques in gynaecology and obstetrics" held 25th and 26th of October, 1990, in Rostock. Surgery of urinary incontinence is not sufficient despite improving choice of methods. Therefore each new solution is welcome. In our times suprapubic colposuspension operations are the most interesting ones. Using fibrin sealing could be advantageous, if it would be possible, to limit sealing area and following tissue consolidation to the pubourethral ligaments. Sealing of fascial sutures and avoiding of vaginal adhesions in cases of vaginal repair would be imaginable. As alternative mobile vaginal suspension by means of fascial strips is demonstrated. PMID- 1621459 TI - [Prenatal diagnosis of truncus arteriosus communis (type I) in diabetic pregnancy]. AB - Recently Ferencz et al. [6] using the datas of the Baltimore-Washington Infant Study found a predominance of double outlet righ ventricle and truncus arteriosus communis among the congenital heart diseases of newborns of diabetic mothers. This paper reports about the prenatal diagnosis of a truncus arteriosus communis Type I in a 23 year old pregnant with insulin-dependent diabetes mellitus (White B). The diagnosis was performed in the 25th week using Real-Time- and Color Doppler-sonography. The important features in the prenatal differentialdiagnosis from a tetralogy of Fallot are explained. The optimal management of pregnancy, the delivery at a perinatal center with subsequent operative correcture could improve the prognosis of the newborn. PMID- 1621460 TI - [Josef Hirsch--pioneer of breast saving therapy of breast cancer]. PMID- 1621461 TI - [115 years Berlin Society of Obstetrics and Gynecology: Carl Ludwig Ernst Schroder, progress and effect. Part III]. AB - 115 years age (1876) in Berlin the Society of obstetrics and gynaecology was founded by fusion of the society of obstetrics (1844) and the society of gynaecology (1873). As first president was elected Carl Schroder, the new ordinarius of the Gynaecological Department (Universitats-Frauenklinik). The present paper descirpt the live and work of Carl Schroder on the background of Berlin Gynaecology in last decades of the XIX. century. PMID- 1621462 TI - [4th Congress of the International Perinatal Doppler Society 29-31 August 1991 in Malmo]. PMID- 1621463 TI - Gross and histopathological observations on the effects of therapeutic ultrasound in experimental acute chemical arthritis in calves. AB - Acute chemical arthritis was induced in right radiocarpal joints of eight cow calves by intraarticular injections of turpentine oil. They were randomly divided into two groups A and B of four calves each. Group A served as control. Group B was given therapeutic ultrasound at 2.0W/cm2 for 7 minutes daily for 7 days starting on day 5. On day 19, all the calves of both the groups were slaughtered. Grossly as well as microscopically, joint tissues of group A calves showed severe inflammatory and degenerative changes. Joint capsule of group B calves showed regeneration of synovial membrane and articular cartilage was normal grossly as well as microscopically. PMID- 1621464 TI - [Evaluation of the postoperative "state of health" using the example of the body core temperature rhythms of sheep]. AB - A postoperative (p.op.) estimation of "healthiness"--especially an estimation of duration of possible existing changes, caused by surgical treatment--is important not only for the ongoing of the healing up process. A re-activation of treated farm or laboratory animals which is set up too early might produce reduction of efficiency or falsification of experimental results. Investigations on p.op. de synchronisation have proved that "healthiness" means--besides the absence of clinical symptoms--also stable relations among the circadian rhythms. As the ultradian rhythms (wavelength less than 24 h) which exist beside the circadian ones depend on endogenic and exogenic factors much more than the circadian rhythms do, the aim of this study was to investigate strength and especially duration of changes p.op. in using core temperature rhythms of sheep as example, by setting great value on investigating ultradian rhythms. The core temperatures of 5 Merino-mixed sheep were permanently measured for 4 weeks p.op. by special radiotelemetric equipment, under controlled circumstances. All recorded data have been expertised "macroscopically" and Fourier-analysis was employed for judging phase shift and intensity of existing rhythms. Though no signs for systemic disturbances could be found and the recorded temperature always was in between the physiological range, important shifts of phases and variations in intensities in the ultradian scope as well as in the circadian one occurred. The "normal" or final phase relations and the constant daily pattern of intensities in sheep were reached 16 days p.op. earliest. PMID- 1621465 TI - The effect of additional feeding on the fertility of high-yielding dairy cows. AB - One hundred and ninety three pairs of cows were selected from 38 herds, and the numbers of each pair were assigned at random to experimental and control groups. Each control cow was fed according to its yield with the feedstuffs normally used by the herd. Each experimental cow was fed in the same way and, in addition, received 500 g of a feed additive twice daily from the 40th day of lactation until first insemination or to the 75th day of lactation if no visible oestrus had been observed between days 40 and 75. One kg of the feed additive contained glucogenic substances (glycerol and Ca-propionate) equivalent to 1.90 moles of glucose, 13.6 MJ metabolizable energy, and 180 g digestible crude protein. There were no significant differences between the groups with respect to their mean daily milk yield, their plasma glucose concentrations at first insemination, or the interval between calving and first insemination. However, the experimental cows had a significantly shorter interval between calving and last insemination (mean difference 11.0 days). The pregnancy rate was significantly higher among cows with high than among cows with low plasma glucose concentrations. There was also a tendency towards a reduced pregnancy rate among cows with either high (greater than 7.0 mmol/litre) or low (less than 4.0 mmol/litre) milk urea concentrations. PMID- 1621466 TI - Comparison of staple and Gambee techniques for enterotomy closure in the normal bovine jejunum. AB - Two suturing techniques for closure of jejunal enterotomies--the stapling and the Gambee technique--were compared in 7 bulls. Stapling was less time consuming (P less than 0.0001) and reduced the overall duration of surgery by 15%. Furthermore, the lumen diameter was significantly less decreased in the stapled intestine at 8 weeks after surgery (P less than 0.05). The diameter of the intestine increased significantly between 8 and 13 weeks after the Gambee suture had been applied (P less than 0.05) and the difference in diameter between intestines sutured according to Gambee and the stapled intestines disappeared. The intestinal diameter did not change significantly between 13 and 18 weeks in both techniques. The application of Gambee sutures resulted in fewer adhesions (P less than 0.01) and less thickening of the intestinal wall (P less than 0.0001). The surgery did not seem to affect the performance of the bulls significantly. PMID- 1621467 TI - Influence of hypertonic saline solution 7.2% on different hematological parameters in awake and anaesthetized ponies. AB - The influence of hypertonic NaCl 7.2% infusion (4 ml/kg of body weight [BWT]) on plasma (PV) and blood (BV) volumes, sodium (Na), chloride (Cl), potassium (K) plasma concentrations, osmolality (Osm), total protein content (TP), packed cell volume (PCV) and red blood cell count (RBC) was studied in five standing and anaesthetized ponies (standard halothane anaesthesia). Arterial blood gases were followed in the anaesthetized ponies. Isotonic NaCl 0.9% (4 ml/kg of BWT) was used as a placebo in the standing ponies. Isotonic solution in the standing ponies induced few changes: only small decreases in K, TP, PCV and RBC were observed. Na, Cl and Osm increased significantly after the NaCl 7.2% infusions in the standing and anesthetized ponies. Significant decreases in PCV, RBC and TP after the administration of hypertonic solutions were determined and were in both groups clear indications of an occurring hemodilution although no significant increase in PV and BV could be demonstrated. An increase in diuresis characterized by numerous micturitions was observed in the standing ponies and during the recovery period after anaesthesia. Apparently, the occurring fluid shift towards the intravascular compartment was partly compensated by an increase in diuresis. The decreases in PCV, RBC and TP were less severe in the anaesthetized ponies compared to the changes observed in the standing ponies. Stress responses during anaesthesia might explain this finding. K increased abnormally at the end of anaesthesia, probably due to minimal muscle damage induced by the dorsal recumbent position. Arterial blood gases did not change after the administration of NaCl 7.2% solution during anaesthesia. No specific clinical side-effects related to the use of hypertonic solution could be observed in the standing and anaesthetized ponies. Further studies are necessary to investigate the effects of hypertonic NaCl solution in horses with a disturbed fluid balance (hypovolemia). PMID- 1621468 TI - Cardiorespiratory parameters in draught horses before and after short term draught work pulling loads. AB - In order to establish the relationship between draught force and cardiorespiratory responses to exercise heart rate (HR), respiratory rate (RR), arterial and venous blood gases, pH, hemoglobin concentration and temperature were measured in five draught horses during rest, immediately after exercise and 30 min post-exercise under field conditions. A wagon equipped with an odometer and a hydraulic dynamometer was used for measuring distance and draught force. The wagon was loaded with 946 kg for the low load, 1,979 kg for the medium load and 2,994 kg for the high load, and drawn for a distance of 1,500 m. Draught force and load weight were linearly related. The response of the draught horse to low and medium load exercise was characterized by a moderate increase in HR, RR and temperature with no significant changes in arterial blood gases and pH. An increase in HR, RR and temperature was observed, whereas no changes in arterial PO2 and increases in venous PO2 were noticed after high load exercise. Slight increase in venous lactic acid concentration as a result of high load exercise was observed, suggesting that some anaerobic work was performed. However this was insufficient to produce changes in blood pH. The increase in metabolic requirements during the three levels of draught exercise was associated with increases in arterial hemoglobin concentration and oxygen content of blood. PMID- 1621469 TI - The metabolism and urinary excretion of orotic acid in hyperargininaemic sheep. AB - The synthesis, blood plasma turnover and urinary excretion of the orotic acid in normo- and hyperargininaemic sheep was investigated. The whole-body orotate formation was evaluated indirectly by the measurement of urinary orotate excretion after blockage of pyrimidine pathway with 6-azauridine (4 hour i.v. infusion of 0.2 mg.kg-1.min-1). Simultaneous infusion of L-arginine (2.5 mumols.kg-1.min-1) significantly elevated the blood plasma arginine, ornithine and urea level, however, it did not significantly influence urinary orotate excretion. In normoargininaemia blood plasma turnover of exogenous orotic acid amounted to 4.9 min and 67% of this compound was eliminated through the kidneys. The renal clearance of orotic acid amounted to 21.7 ml.min-1.kg-0.75. Hyperargininaemia elevated blood plasma turnover to 8.2 min, and diminished the renal clearance of this metabolite to 13.7 ml.min-1.kg-0.75. These results indicate that hyperargininaemia and hyperornithinaemia do not change the whole body synthesis of orotic acid in sheep but they can affect renal excretion of this metabolite, particularly at the rate of tubular secretion close to saturation. PMID- 1621470 TI - [Recording the feeding behavior of freely moving animals using the example of freely diving Weddell seals (Leptonychotes weddellii)]. AB - During the antarctic summer 1990, the pattern of food intake in comparison to diving-activity was investigated on adult Weddell seals. Diving depths were recorded by a time-depth recorder (TDR). The TDR is a free programmable electronic datalogger, which can store data on up to 5 channels. It was fixed on the fur of the seal, ensuring that no longer lasting irritation of the animal was caused. The pattern of food-intake was monitored by measuring the jaw-movements, using strain gauges for recording the deformation of the muscles by mastication. After electronic amplification and filtering, the frequency of jaw-activity within a measuring period was recorded one channel of the TDR. By simultaneously observing the diving depths, these data may lead to conclusions about chewing patterns of the seal in water depths where they catch prey. The graph of these data and the mathematical evaluation by Fourier analysis and Plexogramme show a close correlation between diving depth and jaw-activity. PMID- 1621471 TI - Atlanto-occipital fusion in two polled Hereford calves. AB - Two cases of atlanto-occipital fusion were diagnosed in Polled Hereford calves. The cause, genetic or environmental, of this abnormality could not be determined. Since relatively minor traumatic forces during birth can cause severe injury in the head region, atlanto-occipital fusion should be ruled out in calves dying acutely after assisted parturition. PMID- 1621472 TI - Diagnosis of avian chlamydiosis: specificity of the modified Gimenez staining on smears and comparison of the sensitivity of isolation in eggs and three different cell cultures. AB - For the diagnosis of chlamydiosis in dead and live birds different methods were compared for their sensitivity and specificity. The specificity of the modified Gimenez staining and the direct immunofluorescence (DIF) test for direct demonstration of Chlamydia psittaci in organ, cloacal and/or conjunctival smears was examined. The sensitivity of the isolation of Chlamydia psittaci in 6 days embryonated specific pathogen free (SPF) chicken eggs, Buffalo Green Monkey (BGM) cell line, McCoy cell line and Vero cell line was compared. On smears, the direct immunofluorescence test was more specific than the modified Gimenez staining. The concordance between the results of both detection methods was 80%. The BGM cell culture was the most sensitive artificial host for isolation of Chlamydia psittaci, followed by the embryonated eggs, the Vero cell line and the McCoy cell line. The concordance between the results of isolation in BGM cell culture and eggs was 96.5%, while it was 86% between the results of isolation in BGM cell culture and Vero cell culture and only 65.5% between the results of isolation in BGM cell culture and McCoy cell culture. For dead bird species, chlamydiosis could be diagnosed more often using DIF on smears than with isolation. The concordance between the results of the DIF on smears and isolation followed by DIF was 91%. PMID- 1621473 TI - Occurrence of Campylobacter spp. in young gulls, duration of Campylobacter infection and reinfection by contact. AB - Two groups of three week old Herring Gulls (Larus argentatus) were held to observe the carrier state with Campylobacter. All 27 birds of group I excreted Campylobacter jejuni biotype III when they were caught from their colony. Four weeks later all but one were negative, indicating that the carrier state lasts until about the seventh week of life, with self-elimination if infection with another Campylobacter species is prevented by housing in a closed environment as in this study. Only one bird became reinfected one year later when gulls from group I were brought into contact with gulls from group II, consisting of ten freshly caught gulls, four of which were infected with the same biotype of Campylobacter, indicating that there might be some kind of immunity protection against infection with the same biotype of Campylobacter spp. PMID- 1621474 TI - Relationship between pathological findings and values of haematological and blood chemistry variables in apparently healthy finishing pigs at slaughter. AB - The present study was performed to study possibilities of early decision making for appropriate conveyor-line at future slaughtering of normal, clinically healthy finishing pigs. Blood was collected at slaughter from barrows (n = 112). A meticulous examination for subclinical pathological lesions was performed, revealing 5 groups of subjects listed in order of increasing disease-activity: 1- no real disease-activity; 2--with mild subchronic lesions; 3--with subacute lesions; 4--with abscesses; and 5--with fibrinous-necrotic lesions. Significant differences for values of erythrocyte sedimentation rate (ESR), protein, albumin, globulins, and plasma viscosity appeared to occur in this series. It is suggested that measuring acute phase reactants in blood of slaughtered pigs in the near future may reveal appropriate modern tools for meat inspection and predicting slaughtered animal quality. PMID- 1621475 TI - Cell surface hydrophobicity of Actinomyces pyogenes determined by hexadecane adherence- and salt aggregation studies. AB - Cell surface hydrophobicities of Actinomyces pyogenes were determined by measuring the adherence of the bacteria to hexadecane droplets and by salt aggregation tests. Among 42 A. pyogenes cultures tested 25 (60%) adhered strongly (adherence greater than or equal to 75%) and 17 (40%) less pronounced (adherence between 25-75%) to the hexadecane droplets. Pre-treatment of the bacteria with proteolytic enzymes completely eliminated the adherence properties whereas heat treatment had no effect. The salt aggregation studies revealed that 4 (10%) cultures aggregated in ammonium sulfate solutions of a molarity of 0.05 mol/l, 5 (12%), 14 (33%) and 3 (7%) cultures in ammonium sulfate solutions with molarities of greater than or equal to 1.5 mol/l, greater than or equal to 3 mol/l and greater than or equal to 4.5 mol/l, respectively. No aggregation at all could be observed with 16 (38%) of the cultures. Pronase treatment completely eliminated the salt aggregation reactions, trypsin- and heat treatment had no effect. The results from hexadecane adherence and salt aggregation did not correspond. The differences in surface hydrophobicities, possibly related to adherence properties of A. pyogenes, could be used for epidemiological typing of individual cultures of this bacterial species. PMID- 1621476 TI - Hemolytic interactions of Dermatophilus congolensis. AB - The strains of Dermatophilus congolensis grew on blood agar with washed sheep erythrocytes with marked total hemolysis. In testing for hemolytic interactions they gave a significant synergistic effect of a characteristic shape with Rhodococcus equi and Streptococcus agalactiae, whereas with Staphylococcus aureus producing beta hemolysin and with Staphylococcus aureus producing delta hemolysin a simultaneous synergistic as well as antagonistic effect were observed. First of all a conspicuous inhibition of in the beta hemolysin zone began and then the hemolytic effect of D. congolensis was enhanced. A similar double reaction was also observed with Listeria ivanovii. With delta hemolysin there was an inhibition of the hemolytic effect of D. congolensis and at the same time a synergistic effect could be observed. Also D. congolensis gave a weak synergistic effect with Micrococcus lylae and Listeria monocytogenes, and a further weak antagonistic effect with alpha hemolysin of Staphylococcus aureus, Staphylococcus hyicus, Staphylococcus chromogenes and Micrococcus luteus. No interaction of D. congolensis was established with Corynebacterium pseudotuberculosis. PMID- 1621477 TI - Production of staphylococcal enterotoxins and TSST-1 by coagulase negative staphylococci isolated from ruminant mastitis. AB - The production of staphylococcal enterotoxins (SE) and toxic shock syndrome toxin 1 by 40 coagulase negative staphylococci isolated from sheep, goat and cow mastitis was studied. Both ELISA double sandwich and Western blot were used to detect the production of these toxins. Only two strains of S. xylosus were enterotoxigenic, producing SEC. TSST-1 was seen to be produced by 5 strains of S. xylosus, 1 S. sciuri and 2 S. epidermidis. Results obtained by ELISA and by Western blot agreed in all cases except in one strain of S. epidermidis which was only positive using ELISA. PMID- 1621478 TI - Pathogenicity of Beauveria bassiana in mice. AB - The potential pathogenicity of Beauveria bassiana was examined by intramuscular injection of high (2 x 10(8)) or low (2 x 10(5)) concentrations of conidia spores, into the left or right quadriceps muscles of CD-1 mice, respectively. The injection sites were monitored over a period of 28 days by both microbiological and histopathological methods. Focal muscle necrosis, edema and inflammation occurred rapidly (within 12 hours) at the high dose application (2 x 10(8)) site, but such lesions were far less severe with the low dose spore application (2 x 10(5)). Fungal spores in the high dose site persisted in normal shape for 2 weeks, after which time they began to degenerate. Almost all spores were cleared from the injection site within the 28-day observation period. Spread to other organs of the body was not observed, except by macrophage transport to regional lymph nodes. At the low dose rate, most spores were cleared within 12 h to 2 d, leaving only mild focal edema and inflammation. Viable fungal colonies could be recovered up to 3 d after injection from the high dose site, but only up to 12 h from the low dose site. It was concluded that B. bassiana does not cause infection, nor multiply, nor survive for more than 3 days when injected intramuscularly into healthy mice. PMID- 1621479 TI - Seroprevalence survey for Anaplasma marginale-infection of Austrian cattle. AB - A serologic survey study of 5,076 Austrian cattle farming herds was carried out in the period of December 1988 till March 1990. One animal was randomly selected from each herd and the antibody titer against Anaplasma marginale in blood serum samples was evaluated by means of the complement fixation test. The number of these tested blood samples was 3.6% of 140,081 cattle herd farms of Austria. 109 (2.1%) of the tested animals showed positive titers (1:10) against Anaplasma marginale, in relation to the 140,081 cattle herds 0.08%, 4,786 (94.3%) blood serum samples were sero-negative, 188 (3.8%) reacted anticomplementary. The highest number of antibody-positive animals of 8 tested Austrian districts could be found in Carinthia (46 = 5.7%). In Burgenland all tested sera turned out to be negative. Concerning the distribution of sero-positive animals in Austria it can be stated that a decrease of positive reactors from southern to northern region is evident. A connection between the occurrence of anaplasmosis in Italy, Yugoslavia, Switzerland and Hungary, is postulated as a result of the different systems of keeping cattle in the provinces and the regional increase of tick invasion. Possibly an intensive animal transportation is of importance due to the introduction of the disease mentioned before. The results obtained show that anaplasmosis does occur in different areas of Austria. For control of this disease in Austria it is proposed that all imported cattle should be tested serologically for antibodies against Anaplasma marginale. Other diseases in connection with anemia should be excluded by clinical, serological, blood-, as well as pathological examinations. PMID- 1621480 TI - Potent effect of recombinant growth hormone on bone mineral density and body composition in adults with panhypopituitarism. AB - Six patients (21-50 years) with growth hormone deficiency and panhypopituitarism were given recombinant growth hormone, somatotropin, 0.04-0.1 U.kg.body wt-1.day 1, for 12 months. All patients reported improved well-being with increased working capacity. Bone mineral density, as measured by single photon absorptiometry at two sites on the forearm, showed increased values in 5/6 patients after 12 months when measured at the most distal site (predominantly trabecular bone) and in 4/6 at the more proximal site (predominantly cortical bone). Five patients continued therapy for an additional year and after 18 months a significant increase in bone mineral density was seen at both the distal and proximal sites. The mean annual increase in bone mineral density was 12.0 +/- 0.6 (SEM)% and 3.8 +/- 1.3% at the distal and proximal sites, respectively. In a growth hormone deficient control group without growth hormone therapy, the corresponding values were -2.4 +/- 0.6% and -1.9 +/- 0.4%, respectively. Lean body mass, estimated anthropometrically, increased significantly after 12 months and total body potassium, measured by whole body counting technique, increased in 4/6 patients. During growth hormone treatment, the IGF-1 values were above the mean values for age and 50% of the values were above the mean +2 SD. B-glucose, P insulin, serum IGF-2, procollagen-III peptide and phosphate increased and urea, creatinine and IGF-binding protein-1 decreased during treatment. The beneficial effects of growth hormone substitution, especially on bone mineral density, indicate that growth hormone substitution should be considered in all patients with hypopituitarism and growth hormone deficiency, irrespective of age. PMID- 1621481 TI - Humoral immunity and retrobulbar fibroblasts in endocrine ophthalmopathy. AB - The exact role of retrobulbar fibroblasts in the immunopathogenesis of endocrine ophthalmopathy still remains to be elucidated. To evaluate the in vitro influence of humoral immunity on retrobulbar fibroblasts, the effects of immunoglobulin G as well as of the sera of 50 euthyroid patients with endocrine ophthalmopathy and 30 controls on both porcine and human (patients' and controls') retrobulbar fibroblasts were measured by means of several assays: a colorimetric test involving a heterocyclic chemical, a tetrazolium bromide, was applied to quantify the activity of mitochondrial dehydrogenases; the incorporation of 3H-thymidine was determined as a sensitive parameter for cell proliferation, and an enzyme linked immunosorbent assay was to reveal specific binding of antibodies to the cells. There was consistently no significant difference between patients' (untreated or treated) and controls' IgG to bind to, to activate or to stimulate the proliferation of porcine and human (patients and controls) retrobulbar fibroblasts. The effects of patients' heat-inactivated and non-inactivated sera were indistinguishable from those of the controls. Incubation of autologous sera, however, led to an activation of retrobulbar fibroblasts which was both higher than the median caused by the patients' group and that engendered by incubation of autologous IgG. Yet, a significant role that humoral immunity might play directly on retrobulbar fibroblasts could not be detected in the experiments conducted in this study. PMID- 1621482 TI - Arginine-vasopressin and endothelium-associated proteins in thyroid disease. AB - Plasma concentrations of endothelium-derived proteins (fibronectin and von Willebrand factor), liver synthesized proteins (haptoglobin, transferrin, ceruloplasmin, alpha 1-antitrypsin, antithrombin III and factor VIII-coagulant) and plasma arginine-vasopressin (AVP) were measured in 12 hyperthyroid, 9 hypothyroid and 15 age- and sex-matched normal controls. In hyperthyroid patients the plasma concentrations of AVP and endothelium-associated proteins (EAP) were significantly higher than in the control group (p less than 0.05 and p less than 0.01 respectively). Rendering hyperthyroid patients into the euthyroid state significantly lowered AVP (p less than 0.01), fibronectin (p less than 0.05) and von Willebrand factor (p less than 0.01) compared with pretreatment levels. Hypothyroid patients were studied at diagnosis and after replacement therapy with levothyroxine. Compared with pretreatment values, significant increases were noted in plasma concentrations of von Willebrand factor, fibronectin and AVP (p less than 0.01). With the exception of factor VIII-coagulant, the concentrations of hepatic synthesized proteins did not deviate from normal values in hyperthyroid and hypothyroid patients. Significant correlations were found between serum-free thyroxine on the one hand and the plasma concentrations of fibronectin (p less than 0.005), von Willebrand factor (p less than 0.001) and AVP (p less than 0.0001). Similarly, there was significant correlation between the plasma concentrations of AVP on the one hand and fibronectin (p less than 0.002) and von Willebrand factor (p less than 0.01). The results demonstrate elevated plasma levels of AVP in hyperthyroid patients and an increase during levothyroxine treatment of hypothyroid patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621483 TI - An investigation of LH pulsatility in burned men by bioassay and radioimmunoassay. AB - LH pulsatility studies were performed in six burned patients by removing blood samples at 10 min intervals over a 6 h period. All samples were assayed for LH by bioassay (B-LH), LH by radioimmunoassay (I-LH) and testosterone. Mean serum testosterone concentrations of the burned patients were low (6.7 +/- 1.6 nmol/l). I-LH levels were lower than B-LH in all samples. Frequency of bioactive or immunoreactive pulses as well as mean B-LH and I-LH concentrations were similar to previously published data from normal men examined in the same laboratory. The mean biological activity of LH (expressed as the ratio of B-LH to I-LH, the B:I ratio) was lower in burned subjects (1.9 +/- 0.1) than previously reported in normal men. The B:I ratios of burned men were lower (p less than 0.01) at pulse peaks than at nadirs (1.8 +/- 0.1 vs 2.0 +/- 0.1) and an increase in serum testosterone concentration did not follow an LH peak. Serum testosterone concentrations did not cross-correlate with B-LH or I-LH. This contrasts with the findings in normal subjects where the B:I ratios have been found to be higher at pulse peaks than at nadirs and an increase in serum testosterone concentration follows a pulse peak and serum testosterone cross-correlates with B-LH and I-LH. LH secreted in a pulse peak in normal men may contain a particularly biologically potent form of the molecule but this may not be the case in burned men. PMID- 1621484 TI - Ovulation induction with a single-blind treatment regimen comparing naltrexone, placebo and clomiphene citrate in women with secondary amenorrhea. AB - Secondary amenorrhea is often associated with emotional stress, weight loss, eating disorders or polycystic ovary-like disease. Involvement of the endogenous opioids in the pathophysiology of hypothalamic amenorrhea, by inhibition of hypothalamic GnRH secretion, has been demonstrated in some cases. Chronic blockade of the endogenous opioids with the long-acting opioid antagonist naltrexone could result in increased gonadotropin secretion and ovulation induction in these cases. A single-blind ovulation induction protocol comparing naltrexone, placebo and clomiphene citrate was evaluated in eight patients with secondary amenorrhea. Naltrexone proved not to be more effective than placebo in our study. Only one patient ovulated on naltrexone, one on placebo and four on clomiphene citrate. The latter therapy caused a better endocrine response. In conclusion, although ovulation could be incidentally induced by naltrexone, this drug did not appear to be more successful than placebo and clomiphene citrate for ovulation induction in this population of patients. PMID- 1621485 TI - Evidence of intrathyroidal accumulation of TSH receptor antibody in Graves' disease. AB - To clarify the intrathyroidal accumulation of TSH receptor antibody (TR-ab) produced in the thyroid, adrenalin was injected directly into the thyroid artery of patients with Graves' disease during surgery, allowing serial determination of the TR-ab levels in the thyroidal venous blood. Nine surgical patients (3M and 6F) with Graves' disease and receiving anti-thyroid drugs preoperatively for a period of one to four years were enrolled in this study. Comparison between pre- and posttreatment TR-ab levels revealed continuous increments from the pretreatment levels within 15 min of the injection in five (55.6%) of the nine patients. In three of the five patients, TR-ab levels that had been negative before adrenalin injection became positive 1 min after injection. It is assumed that the increase in the TR-ab level is due to adrenalin-induced constriction of the capillaries in the thyroid tissues, resulting in a voluminous flow of the TR ab retained in the thyroid into the vein. These findings indicate that the TR-ab level in the peripheral blood does not necessarily reflect precisely the abnormal immunological condition in the Graves' thyroid. PMID- 1621486 TI - Hormonal gradients between inferior petrosal sinuses in various pituitary diseases. AB - The aim of this retrospective study was to evaluate the existence of a multihormonal gradient between the inferior petrosal sinuses in various pituitary diseases: Cushing's disease (8 cases), acromegaly (4 cases), prolactinomas (7 cases), GH, PRL-secreting adenoma (1 case), functionless adenoma (2 cases), empty sella (3 cases) and in non-tumoral hyperprolactinemia (5 cases). A significant intersinus gradient (more than 1.4:1) was recorded for GH, ACTH and PRL in 16 patients (80%), but in only 9 patients (45%) out of the 20 with hormone-secreting tumors for TSH, FSH and LH. Moreover, of the 10 patients in the remaining groups, only in two cases was a significant intersinus gradient present: one for GH and one for LH. In conclusion, the finding of a multihormonal release in the inferior petrosal sinus ipsilateral to the adenoma is reported, for the first time, in patients with GH- and PRL-secreting adenomas. The possible explanation for such a finding may be either an increased blood flow in this site of sampling or a pituitary multihormone release through a paracrine mechanism primed by the tumoral hypersecreted hormone. In addition, the pulsatile secretory pattern and the short half-life of polypeptide hormones may contribute to better demonstrate this phenomenon in respect to glycoprotein hormones. PMID- 1621487 TI - Plasma oxytocin during the first and second stages of spontaneous human labour. AB - A technique for complete oxytocinase inhibition has been combined with a rapid serial sampling strategy to determine plasma oxytocin concentrations in twelve women during the early and late first stage and in eight women throughout the second stage of labour. The progress of labour is not related to an increase in oxytocin concentration, uterine contractions are not associated with changes in plasma oxytocin concentration and hypocontractile labour does not appear to be the result of a deficit of oxytocin. The majority of patients do not demonstrate an increase in plasma oxytocin concentration during the second stage of labour; however, a minority produce a large surge immediately before delivery. The results do not support a role for oxytocin during spontaneous labour unless uterine activity is controlled by extremely low plasma hormone concentrations or the uterus becomes sensitive to a constant oxytocin concentration. PMID- 1621488 TI - Brown adipose tissue thermogenesis in testosterone-treated rats. AB - The participation of sexual hormones in body weight regulation is partly accomplished by altering food intake. Nonetheless, female sexual hormones also alter brown adipose tissue thermogenesis in females. This study was aimed to find out if male hormones could alter brown adipose tissue thermogenesis in male rats. Testosterone was administered by means of Silastic capsules in adult male rats acclimated either at 28 degrees C (thermoneutrality) or at 6 degrees C (cold), treatment lasting 15 days. Food intake and body weight gain were reduced by hormonal treatment. However, brown adipose tissue mass, protein content, mitochondrial mass and GDP-binding were unchanged at both environmental temperatures. Accordingly, testosterone participation in body weight regulation is thought to be carried out without altering brown adipose tissue thermogenesis. A reduction in the weight of the sex accessory glands was also observed after cold acclimation. PMID- 1621489 TI - Dose-dependent stimulatory effect of human growth hormone on the strength and collagen deposition of colonic anastomoses in the rat. AB - The effects of treatment with four different doses of biosynthetic human growth hormone (b-hGH; 0.125 mg kg-1 d-1, 0.5 mg kg-1 d-1, 2.0 mg kg-1 d-1, 8.0 mg kg-1 d-1) on the bursting strength and collagen deposition of rat colonic anastomoses were studied. Rats receiving 2.0 mg and 8.0 mg b-hGH demonstrated increases in the pre- and postoperative body weights, and the bursting strength and hydroxyproline content of the anastomotic segments in these groups were significantly higher than controls on day 4 postoperatively. The serum levels of insulin-like growth factor I (IGF-I) were significantly higher than the controls after four days of preoperative treatment in the groups receiving 2.0 mg and 8.0 mg b-hGH, and postoperatively the IGF-I levels were significantly higher than those of the controls in the groups receiving 0.5 mg, 2.0 mg and 8.0 mg b-hGH per kg. Consequently, positive correlations were found between treatment doses of b hGH and anastomotic defatted dry weight, hydroxyproline content and bursting strength of colonic anastomoses. PMID- 1621490 TI - Fetal resorption in rats treated with an antiestrogen in relation to luteal phase nidatory estrogen secretion. AB - Centchroman was administered to rats in relation to luteal phase nidatory estrogen secreted between 21.00 on day 4 and 10.00 on day 5 of pregnancy. A single oral dose of 1.25 mg/kg before the secretion of nidatory estrogen, i.e. until 21.00 on day 4, prevented implantation in 100% of the rats without altering plasma estradiol or progesterone concentration. Administration of a dose of up to 62.5 mg/kg at 10.00 on day 5 even failed to inhibit implantation, but caused dose dependent resorption of implantations. Resorption of all implantations at a dose of 62.5 mg/kg was associated with a decrease in circulating progesterone levels, but was only partially reversed by progesterone or progesterone + estrone supplementation. Apparently normal morulae and blastocysts recovered between days 4 and 10 from rats treated with anti-implantation doses before release of nidatory estrogen, when transferred to the uteri of control rats exhibited lower pregnancy, implantation and development rates with increasing confinement in the genital tract of treated donors. None of the embryos recovered from control or centchroman treated females implanted in the uteri of treated rats. Centchroman administration on day 1, but not on day 5, abolished endometrial receptivity to an artificial stimulus for decidualization. All term fetuses were apparently normal and their weight comparable to that of control fetuses. The study provides evidence of post-implantation fetal resorption, occurring primarily between days 10 and 19 post-coitum, in rats treated with a potent antiestrogen before or immediately after the prenidatory estrogen secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621491 TI - High-dose intravenous immunoglobulin treatment in Graves' ophthalmopathy. PMID- 1621492 TI - Mechanisms of baclofen action on spasticity. AB - This investigation estimated the mechanisms of baclofen action on spasticity using a battery of electromyographic methods. Thirty patients with old post stroke spastic hemiparesis took part in the investigation. They were treated with baclofen-mean daily dose 54.3 alpha 11.6 mg for a mean of 26.3 alpha 4.9 days. A questionnaire for assessment of subjective improvement after treatment used a 5 point scale. For standardization of the neurological examination 5-point scales were used to assess muscle tone, muscle force and tendon reflexes. A battery of electromyographic methods was used to analyse different mechanisms of spasticity: for alpha motoneurone activity--the F wave parameters; for gamma motoneurone activity--the T/H reflex amplitude ratio; for presynaptic inhibition--the ratio of H reflex amplitudes before and after vibration on the achilles tendon (Hvibr./Hmax); for common interneurone activity--the flexor reflex parameters. Our results revealed that baclofen reduces spastically increased muscle tone and Babinski sign. It has no influence on muscle force, tendon reflexes and ankle clonus. Baclofen acts by normalizing the altered interneurone activity and decreasing of alpha motoneurone activity. When spasticity has altered interneurone activity and increased motoneurone activity, it is better to treat with baclofen. PMID- 1621493 TI - Cerebral blood flow findings in moyamoya disease in adults. AB - Three adult patients with moyamoya disease are described. They presented with intracerebral hematoma, cerebral infarction and subarachnoid hemorrhage, respectively. Subarachnoid hemorrhage is rare in moyamoya and is usually the result of aneurysm rupture. No aneurysm was found in our patient. Regional cerebral blood flow (rCBF) and the cerebral perfusion reserve assessed by the acetazolamide test, were significantly reduced in all three patients. The areas with most reduced baseline rCBF and most impaired vasoreactivity did not always correspond to the site of the vascular accident, indicating that these CBF changes were at least in part due to the moyamoya disease and/or its underlying causes, and not solely to the vascular accidents. PMID- 1621494 TI - Allelic heterogeneity in group A xeroderma pigmentosum. AB - The molecular basis of Group A xeroderma pigmentosum was investigated by restriction fragment length polymorphism analysis of PCR-amplified DNA sequences using the two restriction enzymes, endonucleases AlwN I and Hph I. The clones of a patient with Group A xeroderma pigmentosum who had typical symptoms showed a G C substitution at the 3' splice acceptor site of intron 3. However, of the two atypical Group A xeroderma pigmentosum patients with mild skin lesions and minimal neurological abnormalities, the milder one showed homozygosity for the nonsense mutation of exon 6, while the other patient with slightly greater central nervous involvement was shown to be a compound heterozygote for the splicing mutation of intron 3 and the nonsense mutation of exon 6, thus indicating an allelic heterogeneity in group A xeroderma pigmentosum. PMID- 1621495 TI - Neurological complications after thrombolytic treatment for acute myocardial infarction: emphasis on unprecedented manifestations. AB - We examined 348 patients who underwent thrombolytic treatment for acute myocardial infarction. Nine patients (2.58%) developed neurological complications related directly or indirectly to this procedure. Cerebral hemorrhage occurred in 3 patients; 2 patients had transient ischemic attacks, 1 had syncope, another had psychomotor agitation and 2 patients presented seizures during the infusion of the thrombolytic agent, without hemodynamic abnormalities. This latter feature had never been described before. PMID- 1621496 TI - Effects of perineural opioids on nerve conduction of N. suralis in man. AB - In this study the effects of agonist acting drugs (morphine sulphate, fentanyl citrate and meperidine hydrochloride) on nerve conduction were studied in 43 healthy young volunteers divided into four groups randomly. According to analgesic equivalent doses, the first group received 2 mg morphine sulphate, the second group 0.02 mg fentanyl citrate, the third group 20 mg meperidine hydrochloride, and as control the fourth group received 2 ml of saline. The latencies, amplitudes of the responses and nerve conduction velocities were obtained immediately before and every 5 min after injections up to 30 min. No significant change was observed within or among the morphine sulphate, fentanyl citrate and saline groups whereas in the meperidine hydrochloride group the amplitudes diminished significantly and this finding was still apparent at 30 min. Four of the cases displayed complete blocks. Nerve conduction velocity did not change in the other 6 cases. The significant decrement of the amplitude of the compound nerve action potential in the meperidine hydrochloride group is probably due to local anesthetic-like action of this drug. Morphine sulphate, fentanyl citrate or saline did not show this effect. PMID- 1621497 TI - Variations of homovanillic acid levels in ventricular cerebrospinal fluid. AB - We studied the nycterohemeral variations of homovanillic acid (HVA) in ventricular cerebrospinal fluid (CSF) in 24 patients undergoing monitoring of intracranial pressure as part of the normotensive hydrocephalus (NTH) work-up. CSF samples were obtained every 4 h in each patient. The mean individual values of HVA in the ventricular CSF ranged from 133 to 421 ng/ml, and they could not be correlated to any clinical feature. The intraindividual levels of HVA were stable throughout 24 hours, with a variation coefficient inferior to 10% in 63% of cases, and inferior to 20% in all the patients. PMID- 1621498 TI - Endocrine function in multiple sclerosis. AB - In 31 patients with multiple sclerosis (MS) the endocrine functions of the hypothalamus, the pituitary and several peripheral endocrine glands were assessed with a combined pituitary test; 3/31 patients had an endocrine disease: one primary hypothyroidism, one primary amenorrhea and one primary male hypogonadism. We found no patient with endocrine disease of the hypothalamus, the pituitary or the adrenals. However, the poststimulatory secretion of cortisol, growth hormone or thyroid-stimulating hormone was impaired in 7/31 patients, suggesting a possible preclinical endocrine insufficiency in these patients. PMID- 1621499 TI - Attentional processing in cervical spine syndromes. AB - Fifty-four patients suffering from "common whiplash" were compared with 28 patients complaining of cervical spine syndrome caused by rheumatism (Barre-Lieou syndrome). All patients underwent clinical interview and formal testing. Formal testing included personality profile, self ratings of cognitive impairment and well-being, and tasks on divided attention and speed of information processing. In the "common whiplash" group higher relative incidences of adjustment disorder were found. In both groups scoring for divided attention was low. With regard to self-ratings, the group suffering from Barre-Lieou syndrome hardly indicated any problems while the "common whiplash" group showed significant impairment. This difference of self-ratings was assumed to reflect the different modes of development of the investigated syndromes: in the group with cervical syndrome due to rheumatism the condition gradually developed giving the patient the possibility to adapt, while in the "common whiplash" group cervical pathology emerged abruptly by impact injury. Adaptation in the latter group was inadequate which in particular explains the appearance of adjustment disorders amongst "common whiplash" patients. Results indicated that headache due to cervical pathology is likely to be responsible for impaired attentional functioning of "common whiplash" patients. PMID- 1621500 TI - Opsoclonus in a patient with Guillain-Barre syndrome. AB - A 54 year-old woman showed the unusual association of a Guillain-Barre syndrome and opsoclonus, a rare eye movement characterized by involuntary bursts of jerking, ataxic and multidirectional saccades, without an intersaccadic interval. Since opsoclonus is a phenomenon described exclusively in CNS diseases, the case reported supports the hypothesis of CNS involvement in some cases of Guillain Barre syndrome. The latter is generally considered an immune-mediated disease and an immune pathogenesis is also supposed in opsoclonus associated with systemic malignancies; besides, in the patient reported, the self-limiting nature of the disturbance and the lack of MRI lesions suggest that opsoclonus may result from an immune-related phenomenon causing a functional and transitory dysfunction of the CNS. PMID- 1621501 TI - Immunoreactive leukotriene C4 levels in CSF of MS patients. AB - Using a sensitive and specific radioimmunoassay levels of leukotriene (LT)C4-like material were estimated in lumbar cerebrospinal fluid (CSF) samples from patients with multiple sclerosis (MS) in comparison to control patients with or without inflammatory processes in the central nervous system (CNS). Levels of LTC4-like material were significantly elevated (p less than 0.01) in CSF from patients with inflammatory diseases such as meningitis, polyradiculitis or meningoencephalitis (57 +/- 53 pg/ml, n = 16) as compared to those from control patients without inflammatory or immunological CNS diseases (21 +/- 16 pg/ml, n = 42). By contrast, LTC4-like material was 16 +/- 7 pg/ml in first manifestations of MS (n = 7). 21 +/- 16 pg/ml in remitting-relapsing MS (n = 15) and 10 +/- 6 pg/ml in chronic progressive MS (n = 8). These results argue against a significant pathophysiological role of cysteinyl-LT in MS. PMID- 1621502 TI - Malignant meningioma metastasizing through the cerebrospinal pathway. AB - A case of malignant meningioma metastasizing through the cerebrospinal pathway is presented. The primary tumor was a parasagittal malignant meningioma invading into the brain. The tumor seeded to the cerebellopontine angle cistern and thoracic spine after multiple operations. Although this type of tumor borders the CSF, metastasis through the cerebrospinal pathway is rare, and only 18 such cases have been reported (2, 3, 10, 12). PMID- 1621503 TI - The adult and a new late adult forms of neuronal ceroid lipofuscinosis. AB - Three cases of the late adult form of neuronal ceroid lipofuscinosis (NCL) are reported. Two of these are siblings with a late clinical onset at ages 26 and 44 years. The third case, sporadic, has the oldest reported age for the onset of NCL, at 63 years and may be regarded as the first example of the "presenile" form of NCL. The clinical, morphological, histochemical, ultrastructural and genetic features of these three cases are discussed. The literature of the clinicopathological NCL cases with an onset at age of 25 and older is reviewed. The clinical and morphological differences between the late adult form and the presenile form of NCL as well as the difficulties in making the diagnosis are discussed. PMID- 1621504 TI - The role of extracellular matrix in peripheral nerve regeneration: a wound chamber study. AB - A wound chamber model was used for the study of the interaction between axon, Schwann cell and extracellular matrix during peripheral nerve regeneration. Impermeable silicone tubes, 8 mm long and 1.4 mm in internal diameter were sutured to transected rat sciatic nerve and the contents of the tubes were removed at intervals for chemical, histological, immunocytochemical and electron microscopic studies. There was an initial phase of fluid accumulation and the formation of a fibrin/fibronectin clot or cable which connected the cut ends of the nerve. The chamber fluid was shown to have a protein profile similar to that of rat serum. Schwann cells, endothelial cells and fibroblasts migrated first into the cable, apparently mediated by cell-fibrin interaction. Axons buried within the Schwann cell cytoplasm were led into the cable but an axon-fibrin interaction was not observed. After 1 week, the fibrin matrix underwent dissolution, with replacement by collagen. This marked the onset of myelination and the organization of nerve fibers into fascicles. The findings from the present study suggest that the interactions between axon and Schwann cell and between Schwann cell and a changing extracellular matrix are the essential driving force in nerve growth and differentiation during peripheral nerve regeneration. PMID- 1621505 TI - The changing pattern of human immunodeficiency virus-associated cerebral toxoplasmosis: a study of 46 postmortem cases. AB - Frequency, pathogenesis and morphological features of toxoplasmosis were assessed in a consecutive autopsy study. Among 204 patients who died from AIDS in Zurich during 1981-1990, 46 (23%) showed morphological evidence of cerebral toxoplasmosis. In 38 out of 46 cases (83%), toxoplasmosis was restricted to the central nervous system (CNS) and, therefore, pathogenetically classified as reactivation of a latent infection. Acute, systemic toxoplasmosis most frequently involved heart and lungs in addition to the CNS and was observed in 7 cases (15%). These patients probably acquired the infection during HIV-induced immunosuppression. Latent infection with intracerebral tissue cysts but no inflammatory response was present in only one case. Diffuse, necrotizing toxoplasma encephalitis with widespread, confluent areas of necrosis was mainly observed during the early period of the AIDS epidemic and restricted to 6 patients (13%) who did not receive chemotherapy. The majority of patients (83%) had multiple, macroscopically well-circumscribed abscesses with preferential location in the cerebral hemispheres. Of all CNS regions, the rostral basal ganglia were most frequently affected (78% of cases). Since 1989, chronic, burnt out lesions were observed. These were mainly composed of lipid-laden macrophages and immunocytochemistry for Toxoplasma gondii usually failed to detect the parasite. This changing pattern of CNS lesions probably reflects improved clinical management of patients with AIDS. PMID- 1621506 TI - Formation of "dark" (argyrophilic) neurons of various origin proceeds with a common mechanism of biophysical nature (a novel hypothesis). AB - Based on recent findings described in accompanying reports as well as on relevant observations in the literature we hypothesize that: (1) the fundamental elements in the mechanism of the formation of "dark" (argyrophilic) neurons are independent of the causative conditions including post-mortem or in vivo mechanical injuries and various in vivo pathometabolic processes such as blood recirculation following ischemia; (2) the causative conditions, each in its own mechanical or metabolic way, induce the same morphopathological damage at one point only within each affected neuron; (3) this damage spreads throughout the respective somato-dendritic or axonal domain and entails type III argyrophilia; (4) the intraneuronal spread of the morphopathological damage consumes mechanical energy stored by the neurofilaments in the form of a metastable inner structure, and (5) is propagated by a process working, in certain structural and energetical respects, on the domino principle; and (6) the primary neuronal damage caused in the above manner might be secondarily modified in different directions by different postcausation conditions. PMID- 1621507 TI - The effect of age and Alzheimer's disease on pyramidal neuron density in the individual fields of the hippocampal formation. AB - Pyramidal neuron density was determined at autopsy in the brains of 12 neurologically normal patients (age range 6-87 years) and 18 patients with histopathologically confirmed Alzheimer's disease (AD; age range 62-89 years). Paraffin wax sections were cut at the level of the central part of the cornu ammonis and stained with cresyl fast violet. Pyramidal neuron density was determined in the stratum pyramidale of the presubiculum, subiculum, prosubiculum and CA1-4. The width of the stratum pyramidale in these areas was also determined. There was no significant effect of age on pyramidal neuron density in any of the fields of the hippocampal formation. However, there was a significant decrease in pyramidal neuron density in the subiculum (44%), prosubiculum (28%) and CA1 (41%) of AD brains compared to controls. There was no significant effect of AD on pyramidal neuron density in the presubiculum, CA2 and CA3, but in CA4 it increased (23%) significantly. Pyramidal band width decreased significantly with age in the presubiculum but there was no effect of age on any other region of the hippocampal formation investigated. The width of the stratum pyramidale was significantly lower in the presubiculum (19%), subiculum (30%) and CA3 (17%) of AD compared with control brains. These data suggest that a reduction in pyramidal neuron density within the hippocampal formation does not occur in the absence of underlying pathology. In AD, pyramidal neuron loss predominantly occurs from that sector of the hippocampal formation which comprises the subiculum, prosubiculum and CA1. PMID- 1621508 TI - Hippocampal pathology in fatal non-missile human head injury. AB - The hippocampus has been known to be involved in fatal non-missile human head injury, although detailed histopathology of this lesion has yet to be described. This report documents the frequency and distribution of hippocampal damage in a consecutive series of 112 fatal human non-missile head injuries. Damage to the hippocampus was noted in 94 cases (84%). Lesions always involved the CA1 subfield and were bilateral in 70 cases. Other subfields of the hippocampus were involved less frequently. Lesions were focal in the majority of cases (58%). Pathological evidence of high intracranial pressure was present in 86% of the cases. Hypoxic brain damage in other regions of the brain was present in 74% of cases. Thus, the hippocampus is frequently damaged in fatal non-missile human head injury. The pattern of this damage is similar to that observed in experimental head injury. Hypoxia and high intracranial pressure are likely to contribute to the occurrence of human traumatic hippocampal damage but other mechanisms, such as excitotoxicity, are likely to be operative. PMID- 1621509 TI - Affection of the hippocampal granule cells in pontosubicular neuron necrosis. AB - The dentate fascia of the hippocampus was studied in 25 infants with pontosubicular necrosis and in 21 control cases without hypoxic cerebral lesions. Of the control cases 19 were completely normal and 2 showed one single necrotic cell in the granule cell layer. In contrast 15 of the cases with pontosubicular necrosis showed varying degrees of neuronal karyorrhexis in the dentate fascia. The severity of these changes largely parallelled those in the subiculum but there were exceptions to this rule. It is concluded that the dentate fascia is frequently involved in pontosubicular necrosis. PMID- 1621510 TI - Primary leptomeningeal glioma: ultrastructural and laminin immunohistochemical studies. AB - We studied a case of primary leptomeningeal glioma (PLG) on the left parietal lobe of a 74-year-old woman and compared the tissue with heterotopic glial tissue from another case. The PLG tumor consisted of spindle-shaped cells with marked nuclear atypism, which tended to be arranged in a fascicular pattern, and the majority of its cells were positive for glial fibrillary acidic protein. Ultrastructural examination demonstrated that most of the tumor cells contained intermediate filaments and often junctional complexes were present on their plasma membranes. Frequently, basal lamina-like structures surrounding the tumor cell surfaces were observed. Laminin immunohistochemistry clearly demonstrated a fine network of linear positive staining around the cytoplasm and processes of the tumor cells. The ultrastructure of the heterotopic glial tissue consisted of many astrocytes partially surrounded by basal lamina. These findings strongly suggest that PLG is a distinct tumor, which arises from the heterotopic astrocytes within the subarachnoid space. PMID- 1621511 TI - Giant axonal neuropathy: report on a case with focal fiber loss. AB - We report on a 5 1/2 year-old boy with chronic progressive polyneuropathy, ataxia, and pyramidal signs. His hair was not curled. Sural nerve biopsy disclosed many axons enlarged by accumulation of 10-nm neurofilaments and a marked variability in the number of myelinated fibers as well as in the amount of axonal enlargements among different fascicles. These findings and the electrophysiological data were consistent with a giant axonal polyneuropathy with a multifocal fiber loss. PMID- 1621512 TI - Creutzfeldt-Jakob disease with amyloid angiopathy: diagnosis by immunological analyses and transmission experiments. AB - It was difficult to make a definite pathological diagnosis in a 73-year-old man with Creutzfeldt-Jakob disease (CJD) due to extensive amyloid angiopathy which lacked any severe spongiform changes. Immunostaining using anti-prion protein (PrP) antibody revealed fine granular deposits in the gray matter, after hydrolytic autoclaving pretreatment on tissue sections. Western blotting also revealed an abnormal isoform of PrP, but PrP gene analysis did not show any abnormalities. The primary transmission experiments were repeated three times and induced spongiform encephalopathy in a few mice after a long incubation period. PMID- 1621513 TI - Prepontine cyst lined by respiratory epithelium with squamous metaplasia: immunohistochemical and ultrastructural study. AB - An 8.5-year-old female presented with multiple episodes of aseptic meningitis and was found to have a cystic lesion in the prepontine region. Microscopic examination revealed a respiratory-type epithelium with squamous metaplasia. Like its normal analogue in the respiratory tract, the epithelium of these intracranial cysts can undergo squamous metaplasia when chronically irritated. The ultrastructural and immunohistochemical characteristics of the transition from ciliated epithelium to squamous metaplasia are described. PMID- 1621514 TI - The acoustic cortex in Alzheimer's disease. AB - The morphology of the acoustic cortex was studied in light and electron microscopy, in 6 post mortem cases of Alzheimer's disease. Silver impregnation techniques and routine stainings were applied for the study of the cytoarchitecture and the cellular morphology of the acoustic cortex. Samples from every part of the acoustic cortex were processed for electron microscopy. The morphological findings were correlated with those of normal controls of relevant age, as well as with the temporal isocortex of the anterior part of the superior temporal gyrus. Silver impregnation techniques revealed a marked loss of dendritic spines in the second, third and fourth cortical layers. An obvious decrease of the axonic collaterals of the large triangular and round neurons was also seen. Neurofibrillary tangles were found in the soma and the initial part of the axon in a large number of neurons, being more prominent in the neurons of the second and third cortical layers. Senile plaques were dispersed all over the acoustic cortex. Electron microscopy revealed numerous paired helical filaments (PHF) located mostly in the soma and the axons of the large neurons as well as numerous Hirano bodies. Synaptic alterations, such as polymorphism of the synaptic vesicles in the presynaptic terminals, dilatation of the synaptic cleft and accumulation of osmiophilic material in the postsynaptic terminals were seen in numerous synaptic profiles in the acoustic cortex. The rare dendritic spines developed synaptic contact practically only with one presynaptic terminal, in contrast to the normal controls which demonstrated numerous dendritic spines developing synapses with more than one presynaptic terminal. The morphological alterations in the acoustic cortex might explain the profound deficit in verbal memory and the language disturbances that are hallmarks in early cases of Alzheimer's disease. PMID- 1621515 TI - Vitamin K deficiency in infancy: the Japanese experience. PMID- 1621516 TI - Prophylaxis of vitamin K deficiency in infancy. AB - A prospective study was performed in Okazaki, Japan, to attempt to establish a more effective system of prophylaxis for vitamin K deficiency in infancy (VKDI). During the first year, a Normotest (Hepaplastintest) was performed in all infants at one week and at one month of age. Two mg of vitamin K was administered orally to those whose Normotest values were below 40%. i.e., the non-prophylactic administration of vitamin K (NPVK). During the second year of the study, all newborn infants received prophylactic vitamin K (PVK) within 24 hours of birth and at one week of age. The dosage was repeated at one month of age depending on the Normotest value. A total of 7,059 infants, comprising 93.3% of the live births in the city of Okazaki, were enrolled in this study. Data from 5,431 of these infants were used in the analysis of the results. In the NPVK group, 20 of the 2,791 infants had Normotest values below 40% at one month of age while 20 of the 2,640 in the PVK group had low values despite the prophylactic administration of vitamin K. Considering the prevalence of low Normotest values (less than or equal to 40%) at one month of age and the predicted Normotest values, it was concluded that the month of birth (June-September), the age of the mother (21-29 years), the birth order (first-born) and male sex are risk factors for vitamin K deficiency in infancy. PMID- 1621517 TI - Analysis of blood spot 17 alpha-hydroxyprogesterone concentration in premature infants--proposal for cut-off limits in screening for congenital adrenal hyperplasia. AB - Blood Spot 17 alpha-hydroxyprogesterone (17-OHP) concentrations in neonates, especially in premature babies, were determined in relation to 1) the gestational age at birth, 2) the equivalent age of gestation at blood sampling and 3) the birth weight. The 17-OHP concentrations were found to be higher with prematurity. Accordingly, the cut-off limit in screening for congenital adrenal hyperplasia (CAH) in premature infants is proposed as 20 ng/ml. Ideal cut-off limits were set by the equivalent age of gestation at blood sampling. Cut-off limits on the basis of gestational age at birth and birth weight are also suggested, where the sampling age is not so advanced. The rate of false positivity in premature infants can be reduced by this method. PMID- 1621518 TI - Development of sound localization. AB - Perceptual sound localization is determined from differences in time and loudness of signals arriving separately at bilateral ears, with the time difference being the more important one. The author examined the development of sound lateralization using a self-recording device developed by Sato. It measures the sensitivity of sound lateralization on the basis of time and loudness differences separately. Subjects were 59 children aged 2 to 18 years and 12 adults who were audiologically and neurologically normal. Sound stimulus was 500 Hz continuous band noise. (1) The testable rate was increased in children older than the age of 4, and all children over 7 years of age could be tested. (2) Children over 4 years of age could lateralize sound on the basis of time difference. Sensitivity to time differences improved rapidly, showing a steep curve, in children from the ages of 4 to 6, and then increased slowly until adulthood. (3) Sensitivity to loudness differences increased and standard deviation decreased with age. There is a possibility that children aged 4 can discriminate loudness difference almost as well as adults. PMID- 1621519 TI - Severe neonatal nemaline myopathy--histological and histochemical studies of respiratory muscles. AB - The histological and histochemical findings in the respiratory muscles of a patient with severe neonatal nemaline myopathy are described. The patient suffered from frequent pneumonia associated with vomiting due to gastroesophageal reflux and died at 3 months from respiratory failure. The diaphragm was moderately involved and the intercostal muscles mildly involved. Core/targetoid structures were observed in the diaphragm and intercostal muscles. PMID- 1621520 TI - Methicillin-resistant Staphylococcus aureus empyema in children. AB - Over a 14 year period, there were 20 patients who presented with staphylococcal empyema from whom methicillin-resistant Staphylococcus aureus (MRSA) was isolated. Twelve cases were community-acquired and 8 were hospital-acquired infections. Patients were treated with penicillinase-resistant penicillin, cephalosporin or carbapenem in combination with or without aminoglycoside. They were also treated with drainage or thoracentesis. However, they were refractory to treatment and 7 patients, 6 of whom were suffering from bacteremia, died. One bacteremic patient was treated with vancomycin and was cured. In an area of endemic MRSA, vancomycin may be the first choice in the initial treatment of staphylococcal empyema until antimicrobial susceptibility can be determined. PMID- 1621521 TI - An unusual variant of chromosome 16 in three generations. AB - An unusual variant of chromosome 16, 16p+, in three generations is described. This is the first clinical report of 16p+ in Japan. PMID- 1621522 TI - Inherited deficiency of the ninth component of complement associated with streptococcal infection. AB - A 7 year old boy, who presented with streptococcal infection, was found to have a low serum complement level (CH50). The C9 component was undetectable. His CH50 rose to the normal value and remained normal for at least three weeks, but decreased to one-third of the normal level three months later. Family studies were consistent with a familial C9 deficiency, with autosomal co-dominant inheritance. PMID- 1621523 TI - Meningeal malignant melanoma in a child: immunocytological diagnosis. AB - A 10 year old boy, who was thought to have had a traumatic intracranial hemorrhage, was transferred to our Children's Medical Center. In spite of conservative treatment, he developed dysarthria, systemic convulsions, unconsciousness, quadriplegia, and consecutive paralysis of the cranial nerves. Magnetic resonance imaging scans demonstrated areas of increased signal intensity around the brain stem. The cerebrospinal fluid (CSF) contained a few large cells with abundant melanin-like granules, and numerous bizarre cells. The latter were considered to be malignant melanoma cells on immunocytological examination. Chemotherapy with dimethyltriazenoimidazole carboxamide (DTIC) and interferon beta (IFN-beta) was ineffective and he expired. Autopsy revealed diffuse infiltration of malignant melanoma cells into the meninges. We think that immunocytological examination of CSF is advisable for correct and rapid diagnosis. PMID- 1621524 TI - Intravenous gamma-globulin therapy in Diamond-Blackfan anemia. AB - Pure red cell aplasia (PRCA) is a rare disorder of erythrocyte production which is believed to have an autoimmune basis in most cases. Diamond-Blackfan anemia (DBA) is one type of congenital PRCA. Since PRCA has been reported to respond to intravenous gamma-globulin (IVGG) therapy, we administered IVGG to a 2 year old girl with DBA resistant to corticosteroids and observed slight therapeutic effect. PMID- 1621525 TI - Estrogen therapy in Turner's syndrome. AB - Girls with Turner's syndrome are born short, grow slowly, and usually fail to enter puberty spontaneously and to undergo a pubertal growth spurt. The goal of estrogen therapy is to correct estrogen deficiency in a manner that optimizes height potential, permits attainment of normal bone mass, and provides appropriate feminization with minimal risk of adverse effects. The issues to be resolved include the age at which treatment should be begun, the preparation, route of administration, and dosage to be given, the effect on concurrent growth hormone administration, the rate of dose increase during treatment, the timing and nature of progestin administration, and the total duration of treatment. The available data suggest that treatment should be initiated between the ages of 12 and 14 years. The dose-response relationship between growth rate and estrogen dose is biphasic. Optimal growth stimulation for ethinyl estradiol occurs at approximately 100 ng/kg body weight per day, which is below the dose that produces full feminization. Although suboptimal doses of estrogen and growth hormone appear to have additive effects, estrogen causes only a minor increase in the short-term growth response to an optimal dose of growth hormone. The long term effects of estrogen combined with growth hormone are unknown. In the absence of data concerning the outcome of different dose schedules, we treated for 2 years at 100 ng/kg/day of ethinyl estradiol, then double the dose annually until menstruation, at which time cyclic monthly progestin therapy is added (medroxyprogesterone acetate 10 mg daily from days 16 to 25). The importance of estrogen in maintaining normal bone mass suggests that treatment should be lifelong. Current research in our clinic is assessing the long-term effect on adult height of ultra-low-dose treatment (25 to 50 ng/kg/day of ethinyl estradiol) during the childhood years (ages 5 to 11), alone or in conjunction with supplemental growth hormone. PMID- 1621526 TI - Standards for growth and growth velocity in Turner's syndrome. AB - Turner-specific natural growth and growth velocity curves based on the retrospectively surveyed growth data of 704 Japanese patients in a mixed cross sectional and longitudinal mode are reported. There was no significant difference in growth between the patients with karyotype 45,X and non-45,X. Twenty-three patients had a history of genital bleeding between the ages of 11 and 14 years (12 years +/- 9 months). The mean height of the patients with genital bleeding did not differ significantly from that without bleeding from birth until 1 year 3 months of age but thereafter the former were always significantly taller than the latter. The former ceased growing after 18 years; on the other hand the latter were still growing after 18 years and then the final height of each group of patients became almost the same (139.6 +/- 3.5 cm in the former and 139.1 +/- 5.6 cm in the latter). A slight and gentle growth spurt was observed during the expected adolescent period in both groups, with and without genital bleeding. However, the mean height of peak (1.3 +/- 0.95 cm/year) and the mean peak velocity (5.2 +/- 1.1 cm/year) in the patients with genital bleeding were significantly higher than those (0.7 +/- 0.36 and 3.8 +/- 0.6 cm/year, respectively) in the patients without genital bleeding. PMID- 1621527 TI - Characteristics of pubertal growth in Japanese children from the standpoint of skeletal growth. AB - Since the end of the 2nd World War, Japan has seen quite rapid socioeconomical development. With this development the physical size of Japanese children has increased, but the final size, especially the stature, is still shorter than that of Americans or Europeans. Bone maturation velocities were compared among Japanese and Chinese children and adolescents aged 7 to 18 (in 1986) and English TW2-subjects, using the TW2 method. Asian children and adolescents may have a different tempo of skeletal maturation during pubertal growth from that of English children and adolescents. This, probably genetic, difference in the tempo of skeletal maturation, especially that of RUS, between Japanese and English during pubertal growth may be one of the main causes of the final difference in the stature of the two groups. PMID- 1621528 TI - Combined human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) treatment in gonadotropin-deficient males with pituitary dwarfism. AB - The effects of hCG-hMG treatment in 13 boys with pituitary dwarfism associated with gonadotropin deficiency, were assessed. No patients except one showed signs of puberty at a bone age of 13 years or above. The one patient with some signs of puberty did not become fully mature. The hCG-hMG was started at a mean age of 20.4 years. The hCG at a dose of 5,000 IU was injected intramuscularly twice a week and the hMG at a dose of 75 IU was given once a week at first. During treatment, the frequency of hMG injections was increased to twice a week in six patients who still had not produced normal sperm counts. After a mean duration of 19.23 months, spermatozoa appeared in eight patients, of whom four showed more than 20 x 10(6) sperm/ml. Among six patients who did not have normal sperm counts and had increased hMG injections, one produced a pregnancy and four achieved sperm counts of more than 35 x 10(6)/ml. One patient had refractory azoospermia. In 13 boys with growth hormone and gonadotropin deficiency, hCG-hMG treatment produced normal spermatogenesis in nine patients, one of whom fathered a girl. Thus, hCG-hMG treatment, especially twice-a-week injections of both hCG and hMG, appears to be effective for gonadotropin deficiency in males. PMID- 1621530 TI - The roles of community practice-based research. PMID- 1621529 TI - Sports medicine: a research agenda for primary care. PMID- 1621531 TI - Single-subject experimental designs: a practical research alternative for practicing physicians. AB - Single-subject research designs offer a viable alternative to the more customary group-comparison designs. The flexibility and practicality of these designs make them particularly well suited for practicing family physicians interested in testing their clinical hunches. Three designs are described that are feasible in a practice setting: ABAB (reversal), multiple-baseline, and the alternating treatment design. Either visual inspection or statistical approaches can be used to evaluate these designs. By being aware of their limitations and by following simple practical steps, the practicing physician can use these designs to improve care of individual patients while simultaneously contributing to our general knowledge. PMID- 1621532 TI - Community and university--partners in research. AB - Community-based and university-based family practice researchers must come together and merge into a synergistic partnership. Community-based researchers often need the special expertise of university statisticians, epidemiologists, and research methodologists, and the enthusiasm of fellow researchers. University based researchers look to the community for subjects and the all-important factor of generalizability. We must no longer rely on serendipity to bring community- and university-based researchers together. Community-based people must acknowledge their needs and actively seek out assistance. The university-based departments can respond by deliberately starting outreach programs, setting up buddy systems, engaging community research consultants, and tracking residents and urging them to continue to do research. Sentinel networks can increase the depth of involvement community researchers have with their own, and others', projects. Such efforts will lead to a creative interrelationship that will be rewarding and enjoyable for us all. PMID- 1621534 TI - Expectations and satisfaction of runners with injury treatments. AB - Seventy-eight runners competing in three Iowa races were surveyed concerning their most recent running injury for which they sought medical care from a family physician, an orthopedic surgeon, or a podiatrist. Their reasons for choosing a doctor, expectations of care, and satisfaction with treatment received were assessed. Most patients selected the orthopedic (50%) or podiatric (42%) physicians upon the recommendation of other runners; only 13% of the family physicians were selected from recommendations. Orthopedic and podiatric patients were more likely than family physician patients to expect x-rays. There was no difference in overall patient satisfaction with treatment received from the three groups of physicians. The runners felt that all physician groups treated their running injuries equally well. PMID- 1621533 TI - High-school football injuries: effects of a post-halftime warm-up and stretching routine. AB - There are 300,000 to 1,215,000 high-school football injuries each year in the United States. These injuries have an important effect on player participation and health care costs. This study investigates what portion of injuries occur during the third quarter of a game, and if completing a warm-up and stretching routine after halftime reduces the incidence of third-quarter injuries. Intervention-group teams participated in a prescribed three-minute warm-up and stretching routine following the halftime break. The control group received no warm-up and stretching intervention. Fifty-five games with 108 total injuries were examined. Overall, ligament sprains and muscle strains were the most common type of injury (38%). In the nonintervention group, injuries occurred most often in the third quarter. Intervention teams sustained significantly fewer third quarter sprains and strains per game (p less than 0.05), although no significant difference in total third-quarter injuries was noted. These findings suggest an association between post-halftime warm-up and stretching and reduced third quarter sprain and strain injuries. We suggest a larger-scale, randomized confirmatory study. PMID- 1621535 TI - Diagnostic and therapeutic tools for the family physician's office of the 21st century. AB - Several new technologies are available to family physicians; however, numerous factors influence a physician's decision to adopt them. This study sought to determine interests and problems related to adopting new technology. The survey population was a group of family physicians who visited our scientific exhibit at the 1990 meeting of the American Academy of Family Physicians (AAFP). A 13-item questionnaire collected information on their use of and/or interest in technological procedures and equipment. Respondents were interested in a variety of new technological procedures. The most important criteria when considering new technology were training, costs, and office scheduling. The emphasis on outpatient care makes it increasingly important for family physicians to use modern technology in their offices and for departments of family medicine to offer training in these procedures. Our study provides a springboard for a broader discussion of the problems involved in selecting and implementing new technology in family practice. PMID- 1621536 TI - Do-not-resuscitate discussions: a qualitative analysis. AB - The literature to date on Do-Not-Resuscitate (DNR) decision-making is based upon data derived from structured questionnaires, hypothetical scenarios, descriptive epidemiology, or simulated discussions. Lacking in the literature has been a critical examination of the health care professional-patient-family relationship and its impact on decision-making regarding resuscitation. The purpose of this study is to identify and describe organizational and communication factors that affect the process and outcome of DNR discussions and decision-making. Individual and focus-group interviews were conducted with sixteen key informants professionally knowledgeable about resuscitative issues. Thematic analysis of these interviews revealed that a variety of cultural and professional values, as well as previous personal experiences, influenced the assumptions that providers made when engaging in DNR decision-making. Specific recommendations are made to help family physicians identify communication strategies that foster understanding and lead to participatory decisions about resuscitation among patients and families. PMID- 1621537 TI - Failures to keep primary care appointments in Saudi Arabia. AB - A prospective study of sociodemographic characteristics and morbidity of 3,292 patients given appointments at the primary care clinics of King Khalid and King Abdulaziz University Hospitals was conducted in 1990. The appointments were made from one to four weeks before the scheduled visit. After the first visit the patients were then followed up for 4 months to record their characteristics and reasons for failing to keep the appointments. The study showed an appointment failure rate of 29.5%. Telephone calls were made to 15.4% of the nonattenders to ask about their reasons for nonattending. Patients over 65 years old and those in the more highly educated group had the highest rates of default. Failures to keep appointments increased for afternoon sessions and toward the end of the week. The 128 nonattenders variously cited transport difficulties (particularly among women), unclear appointment details, and forgetfulness as main reasons for defaulting. PMID- 1621538 TI - Does practice location or academic connection affect recruitment of patients as research subjects? AB - Recruitment rates of study subjects are important planning and validity issues for many research projects. The Community Cholesterol Survey Project (CCSP) offered an opportunity to examine recruitment rates by type of study practice. The CCSP used six primary care practices (2 urban, 2 suburban, 2 rural), including a suburban academic residency program. Recruitment into the study was performed by a single dietician who followed the same procedure at each site. The overall recruitment rate of subjects was 79%. The residency site had the lowest recruitment rate (59%), which was significantly lower than any of the other sites (79% to 90%, average 84%, p less than 0.001). No demographic factors provided an explanation for this finding. The demographic factors examined included patient age, gender, race, social status, marital status, years in the practice, and presence of underlying medical conditions. These results add to the evidence that recruitment rates in nonacademic practices may be substantially better than those in residency practices and other academic sites. PMID- 1621539 TI - Can NBME scores distinguish students who choose a practice-based clerkship? AB - The National Board of Medical Examiners (NBME) examination Part II scores of students taking a two- to three-month community practice-based third-year family practice clerkship were compared with the scores of comparison students who had been matched on the basis of NBME Part I results. No significant differences between groups were seen for the total score or the scores in medicine or surgery. Significantly higher scores were seen for the clerkship students in the public health section. Significantly lower scores were obtained by this group on the psychiatry section, probably since many of the clerkship students did not take the regular psychiatry clerkship prior to taking the NBME Part II examination. No significant changes were seen in the scores for medicine or surgery. The results for ob/gyn and pediatrics were inconsistent. Taking this community practice-based clerkship appears to provide an equivalent amount of cognitive information. PMID- 1621540 TI - Screening for alcohol abuse in primary care: current status and research needs. AB - Alcohol dependence and abuse are current problems for about 10% of the American population. Patients with alcohol involvement are over-represented in primary care settings. However, a number of these patients may not be detected as being alcohol abusing/dependent by their physicians. Current alcohol screening measures are reviewed. It is likely that a systematic combination of psychosocial self report data and biomedical information can improve detection of alcohol-abusing patients. Future directions for primary care research include further development of psychosocial screening measures, determining common clinical presentations of alcohol-abusing patients, and evaluating the effectiveness of brief counseling and physician education. PMID- 1621541 TI - An epidemiologic study of neural tube defects: Delta County, Michigan, 1969-1988. AB - We determined the incidence of neural tube defects (anencephaly, spina bifida, hydrocephalus) in a rural county in the Upper Peninsula of Michigan because several local physicians perceived that the incidence in this area might be high. To assure that all neural tube defects that occurred were noted, data for the study were collected from hospital birth-log books, patient records of all neural tube defect births, all stillbirth records, and from records of babies transferred to other regional hospitals. A reference group consisting of 10% of all nonneural tube defect births during the 20 years of the study was selected at random and used to make comparisons to the case group. During the twenty-year period 1969-1988, the incidence of neural tube defects (NTDs) was found to be 2.09 per 1000 total births. The incidence of anencephaly was 1.05/1000; of spina bifida, 0.56/1000; and for hydrocephalus, 0.48/1000. Seasonal variations by month of conception were noted for anencephaly and spina bifida, confirming previous findings in the literature. Study results showed that between 1972 and 1976 there was a cluster of NTDs, but the NTD incidence was not statistically different from what might be expected over a twenty-year period. The incidence of NTDs in Delta County was found to be normal for this part of North America. The results of this study indicate that physicians should be cautious when attempting to interpret rare events, which often occur in clusters, leaving the impression that their incidence is excessive. PMID- 1621542 TI - Family practice specialty preference before and after a required clerkship. AB - Medical students' specialty preferences before and after participation in a required third-year family practice (FP) clerkship were compared to National Resident Matching Program (NRMP) results. Of 714 students studied, 18 (2.5%) changed their specialty preference away from FP during the clerkship and 66 (9%) changed their preference to FP. Sixty-nine (70%) of students who maintained a preference for FP pre- and post-clerkship matched in FP. Seventy-two students changed their specialty preference to FP and 19 changed their preference from FP during the clerkship; 32% of each of these groups matched in FP. Those with both pre- and post-clerkship preferences for other specialties matched in FP at a rate of only 4% but constituted 18% of everyone entering the specialty. PMID- 1621543 TI - [Diagnostic evaluation of closed renal trauma]. AB - Renal traumatism is a relevant entity, its early and precise diagnosis having great weight in the initiation of appropriate treatment and its success. All 189 contained renal traumatisms seen in our service between 1981 and 1989, are studied. The purpose of the present work is to determine the diagnostic reliability of the different tests available, chiefly comparing echography versus urography, as well as CT. The method used is measurement of Sensitivity, Specificity and Predictive values, arranged by grades and compared using the squared-chi method (Fisher's exact test). Regarding the primary results we must emphasise the rejection of a void hypothesis in grades II and III with an error level lower than 0.01 for positive predictive values in echography vs. urography; as well as the high values of sensitivity and specificity of CT in high degree traumatisms. To conclude, those traumas where a complementary study is necessary urography may provide more information than echography; although in traumatisms where high degree lesions are suspected, CT will provided the most valuable information. PMID- 1621544 TI - [Renal carcinoma. Our experience of 20 years]. AB - Review of 174 renal parenchyma adenocarcinoma surgically removed over a period of 20 years with follow-up ranging from 1 to 20 years. Age, sex, time from onset of symptoms and treatment, tumour size and cell type did not influence survival. This was improved the lower the stage was at surgery (80% at 5 years in I, 56% in II, 55.5% in III-A, 11% in III-B+C, 0% in IV). The lack of differences in survival between stages II and III-A is conditioned by the fact that III-A included cases with and without perirenal fat involvement but with a common factor of renal vein involvement. Such factor modifies survival with equal local size (80% at 5 years for T1-2 VO and 83% for T1-2 V1; 56% for T3 VO and 44% for T3 V1. Survival for G1+2 was 66% at 5 years, versus 33% for G3+4. Initial therapy was radical nephrectomy with hilar lymphadenectomy, and there was no difference in survival with regard to the access route used. PMID- 1621545 TI - [Prospective study of the effectiveness and side effects of intracavernous prostaglandin E1 versus papaverine or papaverine phentolamine in the diagnosis and treatment of erection dysfunction. Review of the literature]. AB - E1 prostaglandins (E1-PG) by intracavernous injection has been given for diagnostic purposes to 70 randomly selected patients visiting the practice with erectile dysfunction (ED). Sixty-one were suggested to begin a weekly intracavernous self-injection (WICSI) according to the established protocol. Fifty-one patients (83.6%) started the therapy and within an 18-months follow-up interval only 2 (3.27%) preferred to return to papaverine, since 20 patients had previously undergone the papaverine test and 6 were on WICSI with this preparation. Fifty-three patients (75%) achieved complete erection, 8 (11.4%) enough erection to penetrate without manual help, representing a total efficacy of 87%. E1-PG dosage varied from 10 to 40 mcg based on diagnosis, and was readjusted in 6 of the 9 patients which in the initial tests had not obtained sufficient erection, therefore bringing about a final 91.4% erections of sufficient characteristics for intercourse to be considered normal. During the year and a half follow-up a total of 2,880 E1-PG self-injections were injected without during this time cases of priapism, systemic reactions, cavernous bodies infections, arteriovenous fistulae, fibrosis of the cavernous bodies, etc, being observed. Two patients showed prolonged erections of 3-5 hours during the E1-PG tests which remitted spontaneously without sequelae and now continue the WICSI programme after dosage readjustment. In our experience, E1-PG intracavernous injection has proven to be more effective than papaverine in the treatment of erectile dysfunction and therefore, added to its safety and degree of acceptance, we consider it a first choice approach in the diagnosis and treatment of erectile dysfunction in males. PMID- 1621546 TI - [Carcinoma of the penis. Our experience with 22 cases]. AB - The penis carcinoma is a neoplasia representing 0.7% of all male neoplasias, with an annual incidence between 1 and 2 cases per 100,000 inhabitants/year. The present study compiles the authors' experience in treating 22 patients presenting this neoplasia in the period between 1977-90. The procedures carried out included local resection, partial amputation, radical penectomy with lymphadenectomy plus radiotherapy, and palliative surgery plus radiotherapy all based on staging made following TNM grading. Therapy complications, follow-up, and survival results are explained. There were 5 occasions of spinocellular carcinoma co-existing with other neoplasias: 1 colon adenocarcinoma, 1 prostate carcinoma, 1 cleaved small cell centrocytic diffuse lymphoma, and 2 skin epithelioma in other sites, and relevant literature was reviewed. A background of psoriasis treated with psoralens plus UV was present in 4 cases, and caution was advised towards genital protection in patients undergoing UV radiations whether for therapeutic, recreational or cosmetic reasons. PMID- 1621547 TI - [Management of pancreatic lesions in urologic surgery]. AB - Surgical trauma of the pancreas cauda can occur when the renal hilum is dissected during left radical nephrectomy, mainly when normal anatomy is altered by the tumoral or inflammatory pathology. This lesion can be appreciated during the surgical procedure or else a pseudocyst or pancreatic fistula can become evident post-operatively. The urologist's knowledge of what the correct management both intra-operatively and postoperatively of this pathology should include will lessen the significant morbidity it implies. Presentation of a series of 6 patients presenting pancreatic trauma during left radical nephrectomy. Comments on the pathophysiology of this disorder, intra-operative management and post operative treatment, specifically emphasizing the use of Total Parenteral Nutrition and Momatostatin IV. PMID- 1621548 TI - [Predisposing factors for the development of acute severe tubular necrosis in the immediate post-transplantation period]. AB - Retrospective study on the incidence of severe acute tubular necrosis (ATN), defined as the need for dialysis on the first week post-transplantation ruling out acute rejection or technical complication, in our series of 81 renal transplantations from corpse donor. It includes an evaluation of the influence on severe ATN presentation of parameters such as recipient and donor's age, level of plasma creatinine prior to extraction, whether the corpse had hypotension, duration of both vascular anastomosis and procedure, type of removal (single or multiorgan) and cold ischaemia. We conclude that in our experience, cold ischaemia of the graft is the only determining factor among the cases studied for ATN presentation conditioning a reduced long-term survival of the graft (0.758 vs 0.971 at 18 months: p.05). Peripheral blood typing of corpse donor would allow us to shorten cold ischaemia duration, and thus achieve a low rate of severe ATN (13.6%). PMID- 1621549 TI - [True value of the liquid supply and its quality, in the lithiasic population]. AB - The chemical composition of 29 of the bottled mineral waters available in the Spanish market are analyzed, including composition of the tap water supplied by Canal de Isabel II, which provides drinkable water to Madrid with a population close to 5 million inhabitants. The literature relevant to the influence water and its composition may have on the lithiatic prophylaxis is reviewed, exploring data related to our waters, and offering an approach on their use in the different types of lithiasis. PMID- 1621550 TI - [Non-radical treatment and bladder conservation in infiltrating tumor of the bladder]. AB - The fate of some infiltrant tumours of the bladder locally advanced (pT2-3NxM0) which were radically resected, with or without association to other treatments, has been similar to those in which initial radical treated was used. To carry out simultaneously a radical RTU as a local action plus systemic chemotherapy (M VAC), for microscopic metastasis, clinically undetected, seems to us the most effective combination. In our Urology Unit, the evolution (September 88-January 91) of 9 patients presenting this tumour and preservation of the bladder is being followed-up. The primary tumour was treated with radical RTU in 7 cases and partial cystectomy in 2. There are 5 tP2, 1 pT2 + "in situ" carcinoma (Ca) and 3 pT3, 4 G1, 4 G2 and 1 G3. All tumours were single, small (2-4 cm), with varied location and nearly all with medium to low differentiation. Later all patients underwent systemic chemotherapy with M-VAC (3 cycles). Following RTU and QMT every three months, the likely local and systemic progression of the disease has been evaluated through cystoscopy and multiple biopsies including from the prostatic urethra, RTU of anterior scar, two-hand palpation, urinary cytology, blood testing, CAT, abdominal ECO, chest X-ray and laparoscopic lymphadenectomy (coinciding with its development within the Unit) in the last case. Average follow-up (at the time of the review) has been 15.77 months (6-28 months).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621551 TI - [Chyluria of non-parasitic origin. Presentation of a case and review of the literature]. AB - Chyluria is defined as the lymph reflux to the urinary collecting system through fistulous communications secondary to lymphatic stasis caused by obstruction of the lymphatic flow. Filariasis is the most frequent cause of chyluria, which is endemic in some areas, mainly in the Asian continent. In our environment chyluria is extremely rare, most cases being due to non-parasitical causes: tumours, abscesses, trauma, tuberculosis, congenital, etc. A patient case of chyluria in a 39 year-old male with background of chest trauma in which the source of chyluria was discovered to be an obstruction of the chest duct due to post-traumatic aneurysm of the aortic notch. The picture of chyluria ceased immediately after surgery, an aneurysmal resection with replacement with an aortic prosthesis. Considering the infrequency of chyluria in our environment, a literature review is made, explaining the most frequent etiological data, as well as accompanying clinical signs, diagnostic means and conservative and surgical procedures in the treatment of this process. PMID- 1621552 TI - [Cutaneous metastasis of epithelioid sarcoma of the penis: report of a case]. AB - Exposition of one case of skin metastasis in a 35 year-old patient, diagnosed 10 years previously with epithelioid sarcoma of the penis, which was treated with total penectomy. The singularity of this case lies in the rarity of a pineal site for this tumour, as well as the infrequency of the skin metastasis. It should be noted the significance of long-term follow-up in this patients, since quite frequently they develop metastasis following a long asymptomatic period. PMID- 1621553 TI - [Drug-induced fever caused by prophylactic isoniazid in bladder instillations with BCG]. AB - We present of one patient with isolated pharmacological fever probably caused by Isoniazid given prophylactically 24 hours prior to each vesical instillation with BCG as maintenance therapy for in situ vesical carcinoma. The fever appeared in two occasions before the instillation and did not returned once the drug was discontinued. We Review this adverse effect which may lead to diagnostic error. PMID- 1621554 TI - [Kidney pelvis tumor in ectopic kidney. Report of a case]. AB - A case of urothelial carcinoma in pelvic ectopic kidney is described. The low incidence of both pathologies and their rare association justifies the description. PMID- 1621555 TI - [Sjogren's syndrome associated with renal lithiasis. Report of a case and review of the literature]. AB - Presentation of a case of Sjogren syndrome associated to urinary lithiasis. This is a very rare association, of which only 4 cases have been described worldwide, ours being the second report in Spain. Discussion of the pathogenic mechanisms responsible for the urolithiasis, including distal renal tubular acidosis, hypercalciuria and hypocitraturia, as well as therapy followed in this case. Finally, a review is made of the scarce literature available on this rare association, and renal involvement of the syndrome is discussed. PMID- 1621556 TI - [Intradiverticular lithiasis in female urethra. Report of a case]. AB - Presentation of one case of lithiasis as complication of female urethra diverticulum. Etiopathogenic factors, signs and symptoms, diagnosis, complications and therapy options are commented. PMID- 1621557 TI - [Metastasis in maxillary sinus as presentation form of adenocarcinoma of the prostate]. AB - Presentation of one case of prostate adenocarcinoma its initial clinical manifestation being the appearance of facial tumour secondary to metastatic affectation of left maxillar sinus. After stressing its rarity, the relevance of immunohistochemical studies for the specific prostatic antigen and acid phosphatase in determining the unconnected origin of metastatic lesions is addressed. PMID- 1621558 TI - The relationship of assertiveness to college students' safer sex behaviors. AB - Educational programs designed to curtail the present sexually transmitted disease (STD) epidemic emphasize the role of assertiveness in reducing personal risk. This study investigated the relationship between assertiveness tendencies and safer sex behaviors in heterosexual college students. It was predicted that assertiveness would vary positively, and nonassertiveness negatively, with three types of precautionary behaviors: caution about engaging in sexual intimacy, inquiry about a potential partner's STD risk history, and frequency of condom use. A convenience sample of 253 undergraduates (159 females and 94 males) anonymously completed a sexual behavior/demographic questionnaire and the Intimate Relationships Questionnaire (IRQ), designed for this study and involving assertive, nonassertive, and aggressive responses to scenarios relevant to safer sex. The findings confirmed the hypothesized relationships between IRQ assertiveness tendencies and safer sex practices. Gender differences were discovered on the IRQ and in the health-protective behaviors of using caution and inquiring about a prospective partner's STD risk history. Implications for STD prevention strategies are discussed. PMID- 1621559 TI - The Code Blue report: call to action, or unwarranted "dirism"? AB - The Code Blue report, recently issued by a distinguished panel formed by national medical and educational associations, paints a dire picture of the state of adolescent health and recommends far-reaching measures to reverse "dangerous trends." However, analysis of the report's findings reveals serious flaws in its presentation of nearly every youth problem cited, and its recommendations are much less original and workable than portrayed. A more moderate and positive approach toward youth problems is suggested. PMID- 1621560 TI - Deviant adolescent subcultures: assessment strategies and clinical interventions. AB - Alienation is a contributing factor in adolescents' participation in Satanism, the neo-Nazi skinhead movement, and violent street gangs. Many of their needs are met by gang and/or cult affiliation, including a sense of belonging, self-worth, companionship, and excitement. Emphasizing prevention may minimize deviant subculture involvement, but some adolescents require clinical intervention, ranging from a few outpatient sessions to lengthy inpatient hospitalization. Therapists must be knowledgeable about adolescents' involvement, empathic to their circumstances, and sophisticated in the approach to treatment. PMID- 1621561 TI - Educational effects of interscholastic athletic participation on African-American and Hispanic youth. AB - This study examined the educational effects of interscholastic athletic participation on a national, stratified, probability sample of African-American and Hispanic boys and girls drawn from the High School and Beyond Study (U.S. Department of Education, 1987). This two-year longitudinal analysis was based on questionnaire data from 3,686 minority youth who were sophomores in 1980 and seniors in 1982. The independent variable was athletic participation, and the dependent variables included senior year popularity, extracurricular involvement, grades, achievement test performance, dropout rates, and educational expectations. The control variables were socioeconomic status, school location, and sophomore measures of the dependent variables. In general, athletic participation enhanced popularity and contributed to greater involvement in extracurricular activities. Sports participation was generally unrelated to grades and standardized test scores. Depending on school location (i.e., urban, suburban, rural), athletic participation was significantly related to lower dropout rates for some minority youth. High school athletic participation was unrelated to educational expectations in the senior year. These findings show that high school athletic participation was a social resource for many minority youth, but only a modest academic resource for others. Equally clear, however, is the fact that not all racial or ethnic groups reap the same benefits from sport. More importantly, these findings strongly suggest that high school sport should only be considered one of many institutional forces converging in the lives of American minority youth. To assign sport more significance than these findings call for is to run the risk of oversimplifying and trivializing the very complex psychosocial processes which attend high school athletic participation. PMID- 1621562 TI - Psychopathology in incarcerated juvenile delinquents: does it extend beyond externalizing problems? AB - The present study attempted to delineate factors that are associated with and may contribute to juvenile delinquency. Delinquents were compared to a matched control group of nonoffenders on a measure of mental health problems. Twenty-four male and female incarcerated juvenile offenders and 24 nonoffending adolescents were evaluated on the Revised Behavior Problem Checklist (RBPC). As expected, the offenders scored higher (an indication of more psychopathology) on the subscales of the RBPC which represent externalizing types of problems. The offenders also scored significantly higher on the subscales reflecting internalizing problems and psychotic behavior. The results of this study point to the importance of assessing and treating offenders, especially those who are incarcerated, for difficulties other than externalizing problems. PMID- 1621563 TI - Perceptions of parenthood: similarities and differences between 15-year-old girls and boys. AB - Similarities and differences between the contributions of both parents, and some reasons for these similarities and differences, are explored through the responses of a cohort of Dunedin teenagers to questions about their expectations of becoming parents, their relevant experience and knowledge, and their future needs for information. It is concluded that both sexes have a commitment to parenting and expectations of sharing the tasks of parenthood, and that they expect the basis of sharing to be expediency as dictated by economic and other factors rather than any inherent superiority of one sex for the tasks. PMID- 1621564 TI - Development of self-monitoring behavior from early to late adolescence. AB - The purpose of this study was to examine the development of self-monitoring behavior during adolescence. Due to limitations of the widely used Revised Self Monitoring Scale (Lennox & Wolfe, 1984), the construct of self-monitoring has not been successfully examined in individuals younger than college age. For the purpose of expanding our knowledge regarding the developmental aspects of self monitoring, the Adolescent Self-Monitoring Scale (ASMS) was developed, administered to young (junior high) adolescents, and found to be internally consistent and highly correlated with the Revised Self-Monitoring Scale. Factor analysis identified two subscales: (1) Ability to Modify Self-Presentation and (2) Sensitivity to Expressive Behavior of Others. An examination of 490 adolescents from 12 to 18 years of age provided support for the hypothesis that self-monitoring behavior does increase from early to late adolescence. ANOVAs produced a significant difference by age in overall self-monitoring behavior and in sensitivity to the expressive behavior of others. No age differences in the ability to modify self-presentation were found. The development of behavioral measures is suggested to determine more accurately the developmental aspects of the ability to modify self-presentation. PMID- 1621565 TI - Psychosocial characteristics of institutionalized adolescents: resilient or at risk? AB - The primary purpose of this investigation was to provide a psychosocial description of 187 institutionalized adolescents (ages 11-17). The findings suggest that these adolescents may not be as psychologically dysfunctional as is commonly surmised, considering their accumulated life events, family problems, and current displacement. Although the literature is replete with studies that describe characteristics purported to typify at-risk adolescents, there is no substantive demographic base concerning institutionalized adolescents. The authors acknowledge the limitations inherent in their sample and, consequently, offer their findings as a "place to start," and encourage others to follow this line of research. PMID- 1621566 TI - A comparison of the psychological profiles of teenage mothers and their nonmother peers: II. Responses to a set of TAT cards. AB - In Part I of this investigation (Oz, Tari, & Fine, 1992), it was found that, in comparison with nonmother peers, teenage mothers demonstrated a higher degree of ego development. This was in contradiction to most of the literature on the subject. In the second part of the study, the Thematic Apperception Test was employed to examine defenses and motivations which may impact upon the young girls' functioning within family and heterosexual relationships. Results confirmed reports in the literature which have indicated that adolescent mothers attempt to resolve autonomy-dependence conflicts in heterosexual relationships, whereas nonmothers do so within the family of origin. Consistent with their enhanced ego maturity, teenage mothers were more likely to confront their conflicts than were nonmothers. However, whereas nonmothers reacted to environmental stressors by rejecting the source of the stress, teenage mothers tended to react with self-abasement. It is recommended that further research be directed toward uncovering the emotional and cognitive resources of teenage mothers rather than focusing on their more obvious weaknesses. PMID- 1621567 TI - Student evaluation of sex education programs advocating abstinence. AB - This research examined the attitudes of students who were enrolled in three different sex education programs that emphasize abstinence. Data were examined to determine whether secondary school students responded positively to the programs. The programs examined were Values and Choices, Teen Aid, and Sex Respect. Results of the study indicated that all three programs were rated positively, with female, younger (junior high school age), and virgin-naive students rating the programs more highly. PMID- 1621568 TI - Predisposition factors in anorexia nervosa. AB - Since its first recognition, a number of researchers have endeavored to link anorexia nervosa to underlying pathology. For example, in the past, attempts were made to associate anorexia with such psychiatric disturbances as schizophrenia, anxiety disorders, and obsessive-compulsive and antisocial personality disorders. Most recent efforts have focused on the possible link between anorexia nervosa and affective disorders. This article reviews the literature concerned with investigating psychiatric disturbances and genetic variables hypothesized as predisposing factors in the etiology of anorexia nervosa. Particular emphasis is given to research which discusses the association between anorexia nervosa and depression. Psychopharmacological evidence and family genetics studies are reviewed. Suggestions for future research are also made. PMID- 1621569 TI - Runaway girls in distress: motivation, background, and personality. AB - This paper deals with girls aged 13 to 21 who have run away from home. Social workers who work with such girls point out that they are not a homogeneous population and that their motives can be very different. This study divides their motives for running away into two types, "running from" and "running to," and describes the specific personality traits associated with each. Findings indicate that girls who "run to" are younger, more impulsive, have an internal locus of control and a history of more runaways and longer periods of staying away from home. Girls who "run from," on the other hand, are older, more reflective, have an external locus of control and a history of fewer runaways and shorter periods away from home. PMID- 1621570 TI - Attitudes of American youth concerning military and civilian jobs. AB - This study of 306 youths compared the attitudes toward military and civilian jobs among blacks, Hispanics, whites, and Asian-Americans, and for males versus females. Results indicated that blacks and Hispanics, but not Asian-Americans, had a more favorable attitude toward military service than did whites, and males viewed military service more favorably than did females. Military service was seen as patriotic and providing leadership training, while civilian jobs were seen as allowing for more freedom and being more enjoyable. PMID- 1621571 TI - Comparison of public and parochial school patterns of student affect. AB - The MAACL-R scores of 139 middle and senior high public school students (76 females, 63 males) were compared with those of 403 parochial school students (196 females and 207 males). Parochial school students scored significantly higher on depression, hostility, and dysphoria, and significantly lower on positive affect and overall positive mood. Possible explanations for this pattern are discussed. PMID- 1621572 TI - Adolescent parental affinity-seeking: age- and gender-mediated strategy use. AB - The focus of the present study was the use of parental affinity-seeking strategies by adolescents. Both the type of strategies used and the degree to which age and gender factors mediated their use were examined. The results were consistent with Bell and Daly's (1984) constraints dimension of the affinity seeking process, with adolescents employing a narrower range of strategies with the parent as a familiar target. Additionally, significant differences in the use of strategies were apparent on the basis of adolescent's age and gender and parent's gender. PMID- 1621573 TI - The psychosocial characteristics of at-risk high school students. AB - This study examined differences between high school students who were at risk for school failure and a control group of peers. Statistically significant differences were found with respect to locus of control, self-concept, and personal styles of learning. Implications focused upon approaches and suggestions regarding the use of such knowledge in facilitating improved adjustment and achievement in at-risk students. PMID- 1621574 TI - Treating the adolescent victim-turned-offender. AB - Many juvenile sex offenders are also victims of sexual abuse. However, treatment primarily focuses on the juvenile's criminal acts in a confrontational, nonsympathetic manner. In the present paper, a survey of professionals in the sexual abuse treatment field assessed attitudes toward juvenile sex offender treatment. Those in the corrections field were the greatest supporters of confrontational and punitive therapy methods, while the majority favored flexibility in treatment. PMID- 1621575 TI - Dropout--Mertonian or reproduction scheme? AB - This article reports on dropouts in four schools in Israel. Two main research questions were addressed: (1) Is it possible to identify a potential dropout through examination of his/her attitudes and competence before the actual act of leaving school? (2) Is there a difference between dropouts and persistent students in different educational settings (academic, vocational, agricultural, and comprehensive high schools)? Significant differences were found in the attitudes of persistent students and dropouts even before the act of dropping out occurred. In the vocational, comprehensive, and agricultural schools, the dropouts scored more positively on the self-estrangement, meaninglessness, and misfeasance scales. In the academic school, the dropouts scored positively on the anxiety scale. Results were interpreted in light of the Mertonian scheme of ends and means as well as the reproduction scheme. The Mertonian scheme was deemed more applicable. PMID- 1621576 TI - Sources of stress and coping responses of high school students. AB - A series of focus group interviews was used to identify major sources of stress and coping responses of Grade 10 students. Relationships with parents and family, work, and lack of money were found to be important sources of stress. Major coping responses included substance use and diversionary activities. Differences between academic streams (tracks) in sources of stress and coping responses were examined. PMID- 1621577 TI - Adolescent sexual and emotional intimacy. AB - Teenage pregnancy is a major societal concern. Adolescents are sexually active at younger ages and many become mothers and fathers before age sixteen. While much has been written on adolescent sexual intimacy, little has been said about the issue of mature, appropriate, interpersonal emotional intimacy. The present paper addresses this issue and calls for emotional education in addition to sex education. PMID- 1621578 TI - Chinese teenagers' concerns about the future: a cross-national comparison. AB - Teenagers in the U.S., U.S.S.R., Eastern Europe, Western Europe, and New Zealand have consistently rated death of a parent and nuclear war as their greatest concerns about the future. In the present study, however, Chinese teenagers rated overpopulation and environmental pollution as their greatest concerns; these were usually rated quite low by teenagers in other countries. While still of concern to Chinese teenagers, nuclear war seemed more remote to them than it did to U.S. and U.S.S.R. teenagers and therefore more survivable. Speculation is offered as to how teenagers' concerns reflect those of a country's general population. PMID- 1621579 TI - [Vitreous surgery and eye research]. PMID- 1621580 TI - [Gene organization of HLA and its association with ocular disease]. AB - It is now evident that the human major histocompatibility complex (MHC), human leucocyte-associated antigen (HLA), regulates the immune response through discrimination between autologous and non autologous substances thereby displaying a high degree of genetic polymorphism. In recent years, the three dimensional structure of HLA has been clarified by crystal analysis and provides the attractive hypothesis, the so-called hotdog model, explaining the interactions of foreign antigens (or autologous antigens), HLA and T cell receptors and has a great impact on various studies on immunogenetic mechanisms underlying the development of many diseases. Thus, several HLA-associated ocular diseases such as Behcet's disease and Harada's disease have also been analyzed from this point of view by means of recombinant DNA techniques, enabling elucidation of molecular mechanisms of susceptibility to these diseases. This paper describes a general outline of HLA, especially its genetical structure, as well as recent analysis of molecular mechanisms of the predisposition to representative ocular diseases. PMID- 1621581 TI - [Immunoresponses to the external antigen in conjunctival-associated lymphoid tissue]. AB - The local immunity of the ocular surface is governed by conjunctival-associated lymphoid tissue (CALT), secretory IgA and immunocytes. The authors performed a histological investigation of the time-course changes in CALT caused by invasion of antigen to the ocular surface through the instillation of horseradish peroxidase (HRP) into the guinea pig eye. We used PAS staining, peroxidase staining, alkaline phosphatase staining. The lymphoepithelial cells of CALT phagocytized HRP 30-60 min after the instillation, and formed intraepithelial pockets 24 hours after instillation. The follicular area of CALT was strongly positive for alkaline phosphatase 2 weeks after instillation. These changes were considered to be the first step in the manifestation of local immunity on the ocular surface. Each staining technique revealed differences between the lymphoepithelium and conjunctival epithelium, suggesting that lymphoepithelium has characteristics different from those of conjunctival epithelium. PMID- 1621582 TI - [Differences in cataractogenesis according to neodymium-YAG laser injury site]. AB - The author examined morphological changes of the lens induced by mechanical damage with a Q-switch Nd-YAG laser (anterior capsule, anterior subcapsular deep cortex, posterior capsule). In the ruptured anterior capsule group, epithelial cell proliferation covered the ruptured capsule, and separation of posterior subcapsular sutures and swelling of the posterior subcapsular end of lens fiber cells were observed. In the ruptured subcapsular deep cortex group, swollen lens fiber cells were observed in both the anterior subcapsular and the posterior subcapsular cortex. In the ruptured posterior capsule group, the ruptured cortex was not repaired. Swollen lens fiber cells were first recognized in areas surrounding the ruptured capsule, then at the posterior side of the equator, and finally at the anterior subcapsular cortex. The continuity of the lens capsule and lens fiber cells themselves is very important part to maintain lens clarity. The destruction of this feature induced swelling of fiber cells on the opposite side of the injury area. PMID- 1621583 TI - [Effects of prostaglandin E2 on intraocular pressure, anterior chamber depth and blood flow volume of the iris and the ciliary body in rabbit eyes]. AB - The effects of prostaglandin E2 (PGE2) on intraocular pressure (IOP), anterior chamber depth, and blood flow volume of the iris and the ciliary body of albino rabbits were investigated. Swelling and marked capillary dilatation of the ciliary body were observed after topical application of PGE2. IOP increased immediately by 200 micrograms, 400 micrograms, and 1,000 micrograms of PGE2, reached a peak within 30 minutes; then decreased gradually. The anterior chamber depth decreased only at 5 and 10 minutes after 1,000 micrograms of PGE2. The blood flow volume of the iris and the ciliary body immediately increased, and kept it up for 3 hours. Changes of IOP may be associated with an increase of blood flow attendant upon capillary dilatation of the ciliary body, and an increase of aqueous outflow due to breakdown of the blood-aqueous barrier. In addition to morphological and functional changes of the ciliary body, further factors which promote vitreous volume expansion may play an essential part in the development of malignant glaucoma. PMID- 1621584 TI - [The intraocular pressure lowering effects of UF-021, a novel prostaglandin related compound, in animals]. AB - The ophthalmic solution of UF-021, a novel prostaglandin (PG) related compound, was investigated for its intraocular pressure (IOP) reducing activity and local ocular side effects in different species of animals. UF-021 ophthalmic solution (0.03 to 0.24%), when topically applied to the eyes of rabbits, caused dose dependent IOP reduction (2.8 to 5.2 mmHg), without transient IOP rise. Both in cats and monkeys, UF-021 ophthalmic solution (0.12%) elicited rapid, significant IOP reduction (ca. 9 mmHg and 2 mmHg, respectively), without any controversial, local ocular side effects being revealed. On the other hand, PGE2, PGF2 alpha isopropyl ester all brought about marked increases in IOP prior to development of their IOP reducing activities. In addition, these primary PGs showed intense local ocular irritation, which presented a striking contrast with UF-021. Enhancement of IOP reducing activity, coupled with freedom from any significant ocular side effects, as described above, suggests that UF-021 ophthalmic solution could be promising as a new anti-glaucoma agent. PMID- 1621585 TI - [Effects of endothelin on retinal blood vessels]. AB - Endothelins (ETs), which are one of the most potent vasoconstrictors, were discovered in 1988. ETs are involved in the regulation of vascular smooth muscle and are thought to function like a local hormone. In this study, we measured changes in the caliber of retinal blood vessels caused by the intravitreal injection of ET 1 in rabbits, using fundus photography. The retinal artery showed an immediate vasoconstriction after the injection (0.1 ml) of ET 1 at 10(-6)M. However, ET 1 in lower concentrations (10(-7)M and 10(-8)M) caused vasodilations initially and subsequently vasoconstrictions. A dose-response relation was found. The blood vessel caliber reduced maximumly to 53% the value before injection. The vasoconstriction due to ET 1 may induce retinal ischemia and hypoxia. We speculate that ET 1 may be involved in the regulation of retinal blood vessels. PMID- 1621586 TI - [Light response of the interphotoreceptor matrix in inherited degenerative retina]. AB - The light-evoked distributional changes of the interphotoreceptor matrix (IPM) in mice with three types of inherited retinal degeneration were examined by histochemistry using fluorescence isocyanate-labeled wheat germ agglutinin. In mice with nervous and Purkinje cell degeneration, the light response of the IPM was still somewhat preserved during the early stage of photoreceptor degeneration, whereas it became extinct when the outer segments (OS) became moderately or markedly shortened. In mice with slow retinal degeneration mice without development of OS, the light response of the IPM was absent throughout the developmental stages. These findings suggest that the presence of normal OS is necessary for the light response of the IPM to occur. PMID- 1621587 TI - [Retinochoroidal adhesions of diode laser endophotocoagulation lesions. 1. Histopathology of rabbit eyes]. AB - I experimented with a prototype diode laser in order to determine how effective it is for intraocular endophotocoagulation of the retina and how much energy is required to produce chorioretinal adhesions. Retinal endophotocoagulation was performed in all 8 eyes of 4 rabbits. I used power settings at 100-140, 200 and 300 mW and an exposure time of 0.2 seconds. The lesions produced with powers of 100-140 mW were faint whitish spots surrounded by grayish rings. One month after photocoagulation, there were chorioretinal adhesions histologically. The lesions produced with powers of 200-300 mW were characterized by intense whitish spots surrounded by grayish rings and histologically they were over-irradiated ones. One month after photocoagulation, rupture of the internal limiting membrane could be seen in one of the 300 mW lesions. It can be said that the retinal burn which appeared ophthalmoscopically as a faint whitish spot surrounded by a grayish ring may be the most useful to produce chorioretinal adhesion. PMID- 1621588 TI - [Age effects of topical tyramine and cocaine on the pupil]. AB - In order to obtain the age distribution of normal values of the effects of topical tyramine or cocaine on the pupil, we measured the pupillary light reflexes of 50 normal volunteers before and 45 minutes (tyramine) or 90 minutes (cocaine) after the topical instillation in right eyes. Left eyes were used as controls. An infrared videopupillogram (HTV-C301) was used. Topical tyramine as well as cocaine caused mydriasis, increase of maximum %-velocity of dilatation (% VDmax), reduction of %-amplitude of constriction (%-A) and decrease of maximum % velocity of constriction (%-VCmax). These alternations of pupillary parameters coincided with the changes induced by topical epinephrine. The effects of tyramine or cocaine significantly increased as the age of the subjects increased, though the increase of %-VDmax caused by cocaine was only related to age. Age related augmentation of pupillary changes were also been observed in a previous study using topical epinephrine or topical pilocarpine which concluded that the effects of any topical autonomics were increased by aging. No physiological senile Horner's syndrome was detected. It was concluded that the age-related augmentation of pupillary changes caused by topical autonomics probably resulted from the increment of corneal permeability in the aged which was confirmed in the previous fluorophotometric study by the authors following topical fluorescein administration. It is possible to assess the pupillary sensitivity to topical adrenergics of the patients with bilateral Horner's syndrome by comparing the age related normal values obtained in this study. PMID- 1621589 TI - [Subjective detection of visual field defects using the noise-field on a home TV set in low-tension glaucoma]. AB - The usefulness of the Noise-Field Test was studied in 196 normal eyes and 146 eyes of low-tension glaucoma patients (including 74 eyes of early glaucoma) who had never perceived their filed defects. The noise-field spontaneously generated on a 21-inch home television screen through a non-transmitting channel was utilized for the test. A white mark 5 mm in diameter was stuck on the center of the screen as a fixation point. At a distance of 30 cm, the subjects were asked to watch the screen, gazing at the fixation point with one eye for 3-5 seconds, checking to see whether the flickering area on the noise-field diminished or disappeared. The test was performed 3 times on each eye. In 136 glaucoma eyes, the field defects detected by static perimetry (Humphrey) were clearly identified in the Noise-Field Test. In normal eyes, a scotoma was noted on the blind spot in 6 eyes, The sensitivity and specificity was 93.2% and 96.9%, respectively. The Noise-Field Test can be an excellent method in screening for low-tension glaucoma which is easily missed by tonometric screening only. PMID- 1621590 TI - [A mechanism for reducing intraocular pressure in normal volunteers using UF-021, a prostaglandin-related compound]. AB - The mechanism of reduction of intraocular pressure (IOP) and other ocular effects were studies after topical application of prostaglandin (PG) F2 alpha and UF-021, a new PG related compound, in eight normal volunteers. IOP, aqueous humor flow rate and outflow rate were evaluated during a period of four hours after the application. Both PGF2 alpha and UF-021 caused significant and similar IOP reduction for four hours. Neither compound produced any significant change in the aqueous humor flow rate or outflow rate, suggesting the increase of unconventional outflow rate as being the possible mechanism of IOP reduction in normal human eyes. PMID- 1621591 TI - [The diagnosis of sarcoidosis based on ocular manifestations]. AB - A total of 131 patients with typical ocular manifestations of sarcoidosis were studied. From systemic examinations, 56 cases were confirmed histologically as sarcoidosis, 59 cases were clinically diagnosed as sarcoidosis and 16 cases were not diagnosed as sarcoidosis. There were no differences among the three groups in terms of laterality of eye involvement, sex distribution, ocular findings and prognosis. The only difference was that the age of patients not diagnosed as sarcoidosis was lower than the other two groups. In systemic examinations, patients diagnosed as sarcoidosis histologically or clinically had higher ratios of positive findings of bilateral hilar lymphadenopathy, 67Ga scanning, bronchoalveolar lavage fluid and serum angiotensin converting enzyme than patients who were not diagnosed as sarcoidosis. Some cases of the third group may be diagnosed as sarcoidosis in the future by repeated systemic examinations. The difficulty of diagnosis of sarcoidosis from ocular findings alone was discussed. PMID- 1621592 TI - [The immunosuppressive acidic protein in the vitreous of fundus diseases]. AB - Immunosuppressive acidic protein (IAP) is known to be a useful marker for malignant tumors and inflammatory diseases. We have previously reported that serum IAP level was increased in cases of Behcet's disease, especially in the acute phase, and those of retinoblastoma with extraocular infiltration. We assayed IAP levels in the vitreous body of various ocular diseases, including five cases of proliferative vitreoretinopathy (PVR), five cases of vitreous hemorrhage including four cases of branch retinal vein occlusion (BRVO) and one case of Terson's syndrome, four cases of proliferative diabetic retinopathy (PDR) and five cases of acute retinal necrosis syndrome. The single radial immunodiffusion method was used. The vitreous IAP level ranged from 5 to 130 micrograms/ml according to each case. Statistical analysis revealed that the vitreous IAP level was significantly higher in the group of PDR (p less than 0.05) and in the group of acute retinal necrosis syndrome (p less than 0.01) compared to the group of vitreous hemorrhage. In all cases, serum IAP levels were within normal limits. These results suggested that IAP might be produced within the ocular tissue, possibly by the activation of suppressor macrophages and migration of polymorphonuclear leukocytes in the vitreous with pathologic condition. PMID- 1621593 TI - [Vitreous oxygen tension of proliferative diabetic retinopathy]. AB - The authors investigated the vitreous oxygen tension in 30 eyes of 29 cases of proliferative diabetic retinopathy patients in order to determine the distribution of oxygen tension and the possible role of neovascular tissue in tissue oxygenation. Vitreous oxygen tension was measured using a polarographic oxygen electrode and a PO2 monitoring system (PO-2080). Prior to pars plana vitrectomy, the oxygen electrode was inserted into the vitreous cavity under microscopic observation with dim illumination transmitted fiberoptically. The respective oxygen tension at the mid-vitreous cavity, above the optic disc, above the macula, above the neovascular tissue, in the peripheral vitreous, above the photocoagulated retina and above the non-photocoagulated retina were 15.8 +/- 4.7 mmHg, 31.2 +/- 10.0 mmHg, 17.1 +/- 4.0 mmHg, 32.0 +/- 9.9 mmHg, 15.6 +/- 5.1 mmHg, 16.5 +/- 5.5 mmHg and 18.6 +/- 4.9 mmHg. The oxygen tension values above the neovascular tissue and above the optic disc showed statistically significantly higher values than that of midvitreous cavity. We assume this to be due to differences between the oxygen demand and supply on the neovascular tissue, because in these tissues there are large amounts of vessels and blood flow compared to oxygen consumption. Therefore residual oxygen causes oxygen flow from the neovascularization to the mid-vitreous. This outcome is one of the facts which supports the hypothesis that neovascular tissues develop in order to compensate for retinal ischemia by releasing oxygen. PMID- 1621594 TI - [Electrically evoked responses in patients with macular holes]. AB - The Electrically Evoked Response (EER) was analyzed in 7 patients with macular holes in order to determine whether EER reflects macular function. The EER was recorded from an occipital electrode (Oz) by applying a constant electric current of 1.0 mA with a duration of 5 msec and frequency of 1.85 Hz. In five patients with unilateral complete break of macula, each amplitude for the P2 component from the affected eyes was significantly smaller than that from contralateral eyes. However there was no such difference in both eyes of two patients with bilateral macular holes. No significant difference was shown in the amplitude for the P1 and P3 components of EER. These results strongly suggest that the retinal origin of P2 may mainly be in the macular area and that analysis of P2 might be useful to determine further clinical applications of EER. PMID- 1621595 TI - [The properties of visual functions and familial analysis in blue cone monochromatism]. AB - The diagnosis of blue cone monochromatism (BCM) is based on severely affected color vision with preserved blue function, nearly absent photopic ERG, and a family pedigree compatible with X-linked inheritance. In the past, there has been no familial report of BCM in Japan. We found a Japanese family with BCM and studied the ocular findings of three affected members and a female carrier. Two of three affected members showed unique properties of BCM in their visual functions, including color vision and ERG. One affected member, a brother of their mother (43 years old), showed achromatic color vision. He had diabetic retinopathy and moderate cataract, which, might have disturbed his preserved blue cone function, resulting in the achromatic vision. A female carrier showed normal visual function, except that her photopic ERG was slightly reduced in amplitude. PMID- 1621597 TI - [The cytopathological features of the pseudohypopyon in a patient with acute monoblastic leukemia]. AB - The authors cytopathologically examined pseudohypopyon in a 10 year-old boy with acute monoblastic leukemia. The ultrastructural investigation showed that the stage of leukemic cells was monoblastic, which resembled promonocytes. The ultrastructural findings of pseudohypopyon in acute monoblastic leukemia has never been reported. PMID- 1621596 TI - [Control of blood pressure by a calcium antagonist during cataract surgery]. AB - The authors evaluated the systemic and ocular hypotensive effects of nicardipine hydrochloride (Perdipine:NH) in 31 cases with acute hypertension (over 160/95 mmHg) during cataract surgery. All cases received an intravenous bolus injection of NH 30 micrograms/kg. Blood pressure and intraocular pressure were compared with level at rest, a preoperatively and 5 minutes after the administration of NH. Blood pressure significantly elevated from 136.9 +/- 10.6/73.4 +/- 10.2 mmHg at rest to 187 +/- 11.5/98 +/- 13.1 mmHg preoperatively (p less than 0.001), but it significantly reduced to 125.6 +/- 13.1/67.1 +/- 8.3 mmHg 5 minutes after the administration of NH (p less than 0.001). On the other hand, in the same way an blood pressure changed, intraocular pressure significantly elevated from 13.3 +/- 2.8 mmHg at rest to 19.8 +/- 2.9 mmHg preoperatively (p less than 0.001), but significantly reduced 17.1 +/- 3.0 mmHg 5 minutes after administration of NH (p less than 0.001). The hypotensive effect of NH continued for over 90 minutes. There were no side effects apart from mild tachycardia in all cases. NH is safe, easy to administer and useful for control of acute hypertension during limited period surgery such as cataract surgery. PMID- 1621598 TI - [Two cases of isolated avulsed retinal vessels]. AB - Two cases of isolated avulsed retinal vessels without retinal breaks or any other vitreoretinal disorders are reported. Case 1: a 57-year-old woman developed acute vitreous hemorrhages in the right eye associated with an avulsed retinal artery in the superior equatorial region. Case 2: a 74-year-old man had an asymptomatic avulsed retinal vein in the superior midperiphery. Repeat argon laser photocoagulation resulted in uncomplicated occlusion of the avulsed retinal vessels and reduced the risk of recurrent vitreous hemorrhage. PMID- 1621599 TI - [Experimental autoimmune uveitis]. PMID- 1621600 TI - [Studies on ocular alkali burn estimated by the component change of tear fluid and aqueous humor]. AB - In this report, we aimed at examining biochemically the ocular surface damage caused by alkali burn. We used a low concentration of NaOH (less than 0.1 N) and examined the relationship between the ocular surface damage and the concentration of NaOH by examining the changes in components that have been released from corneoconjunctival tissues to the tear fluids by alkali burns, and we also examined the effects of eye rinsing and using topical ophthalmic agents. As a result, NaOH of more than 0.03 N was proven to cause the ocular surface damage. The changes of glutathione in tear fluids showed two peaks during the repair process and that coincided with the morphological changes. By measuring the released quantities of three components (glutathione, ascorbic acid and protein) with the use of three methods of alkali burns (corneoconjunctival pooling method, corneal cylinder method and conjunctival pooling method), we could estimate the slight corneoconjunctival damage using one sample biochemically. Moreover, the importance of eye rinsing was quantitatively demonstrated. PMID- 1621601 TI - [Epidermal growth factor receptor in conjunctiva]. AB - Epidermal growth factor receptor (EGFR) was studied in conjunctiva. Two specimens of normal conjunctiva and eleven of diseases ones, consisting of 2 pingueculas, 4 healing traumatic conjunctiva , and 5 proliferative disorders, were studied immunohistochemically using rabbit anti-human EGFR antibody with avitin-biotin and diaminobentizin method. These investigations revealed that the immunoreactive EGFR was identified only in the conjunctiva of 2 of the 3 cases of granuloma following pterygium surgery but not in the other specimens, including the normal conjunctiva. This fact suggests that abnormal expression of the EGFR could play a role in pathological status of conjunctiva. PMID- 1621602 TI - [Power spectral analysis of electromyograms in fast and slow fibers of cats extraocular muscles]. AB - Electromyogram (EMG) was recorded from the muscle fibers in the orbital layers through the global layers of superior rectus muscle of the cat. Power spectrum analysis was applied to investigate the quantitative differences between EMG patterns in both layers. The median of the power spectrum in frequency from the global layers was 400-700 Hz, which was considered to be an EMG pattern of the fast fibers. On the other hand, EMG from the orbital layers showed a small amplitude of 35-70 microV and two different types of power spectrum; one had the median frequency of more than 1,000 Hz and the other, about 500 Hz. It was suggested that the high frequency component was due to multi-innervated slow fibers and the low frequency component was due to singly innervated and intermediate fibers. The study of the power spectrum of interference electromyograms provides an advantage to differentiate the electrical activities of the slow fibers from the fast ones. PMID- 1621603 TI - [Effects of atropine on acetylcholine levels in the rat iris-ciliary body]. AB - In an attempt to estimate the in vivo acetylcholine level in rat iris-ciliary body, animals were sacrificed by microwave irradiation which rapidly inactivates metabolic enzymes. Acetylcholine levels in the iris-ciliary body were determined by high-performance liquid chromatography with electrochemical detection. The acetylcholine level in rat iris-ciliary body per gram tissue protein was 58.8 +/- 5.0 nmol/g (mean +/- SEM, n = 9). A single instillation of 5 microliters of an 0.05% atropine to one eye of a rat decreased acetylcholine level in the iris ciliary body by 17% half an hour after administration (p less than 0.02). PMID- 1621604 TI - [A novel model of autoimmune uveo-retinitis in nude mice grafted with embryonic rat thymuses]. AB - When the T cell functions of congenitally athymic nude (nu/nu) mice were reconstituted by implantation of embryonic rat thymi (thymus grafted nude mice), uveoretinitis histologically characterized by complete loss of photoreceptor layer was found to develop spontaneously in 4.0, 18.2, 42. 9 and 70.4% of the mice at 3, 5, 7 and 12 months of age, respectively. In mice with uveoretinitis serum IgG antibody reacted with the retinal photoreceptor layer, and with interphotoreceptor retinoid-binding protein, but not with retinal S-antigen by immunoblot analysis and ELISA. The lesions could be transferred to syngeneic nude mice by splenic CD4+ T cells. This suggest that an autoimmune response to IRBP induced the uveoretinitis in thymus grafted nude mice. PMID- 1621605 TI - [Suppression of interphotoreceptor retinoid-binding protein (IRBP)-induced experimental autoimmune uveitis by pretreatment with anti-idiotypic monoclonal antibody]. AB - In an experimental model of interphotoreceptor retinoid binding protein (IRBP) induced experimental autoimmune uveitis (EAU) in Lewis rats, EAU onset was suppressed by pretreatment with anti-idiotypic antibody (TRD3). In the pretreated group, the titers of anti-IRBP antibody and idiotypic antibody were lower and the titer of anti-idiotypic antibody was higher than in the control group, and the skin test (DTH) against IRBP was also suppressed. Histopathological findings of the control group showed destruction of retinal outer granular layer, loss of the outer segment and lymphocytic infiltration, although no definite inflammatory signs appeared in the pretreated group. We suppose that the mechanism of idiotypic suppression is via induction of idiotype-specific or idiotype-related suppressor T cells. PMID- 1621606 TI - [Experimental proliferative vitreoretinopathy in rabbits after intravitreous gas injection and creation of retinal hole: ophthalmic findings and localization of fibronectin]. AB - An animal model of rhegmatogenous retinal detachment and proliferative vitreoretinopathy (PVR) has been developed by the creation of a retinal hole (4 disc diameter) 4 days after the intravitreous injection of 0.4 ml of 100% of perfluoropropane (C3F8) in pigmented rabbits. Ophthalmic and histological examination showed detached retina with associated preretinal, intravitreous membranes containing pigmented fibroblast-like cells. Fibrovascular membranes were noted within the puckered medullary wings. Fluorescein angiography revealed profuse leakage from detached medullary wings. Using immunofluorescence, fibronectin was localized on preretinal, intravitreous, and fibrovascular membranes. These results suggested that the breakdown of the blood-retinal barrier and fibrovascular proliferation in addition of previously recognized cell types may be the important factors in this reliable model of PVR. PMID- 1621607 TI - [Histopathology of retinochoroidal adhesions of diode laser endophotocoagulation lesions in monkey eyes]. AB - Retinochoroidal coagulation effect of 810 nm diode laser was studied using monkey eyes to determine the energy necessary to produce retinochoroidal adhesion safely. Power settings were at 100, 200 and 300 mW. The lesions produced with a power of 100 mW were faint grayish spots. One month after photocoagulation, there was degeneration from the outer granular layer to the superficial choroidal layer. However, chorioretinal adhesion was not obtained due to external limiting membrane formation. The lesions produced with a power of 200 mW were characterized by small whitish spots surrounded by grayish rings and retinochoroidal adhesions were produced by proliferated cells. However choroid were intensely coagulated, and there was a rupture of Bruch's membrane in one lesion. The lesions produced with a power of 300 mW were intense white spots surrounded by grayish rings. Histologically, severe cell loss of the retina was seen and three was no retinochoroidal adhesion. It can be said that it is difficult for 810 nm diode laser to obtain adequate retinochoroidal adhesion safely. PMID- 1621608 TI - [The viability of the detached retina of the rabbit eye--electrophysiological observation of influence of duration of the detachment]. AB - The influence of the duration of the retinal detachment on the function of detached retina was electrophysiologically investigated in the rabbit eye. Experimental retinal detachment with a diameter of 4 mm was made by injecting sodium hyaluronate into the subretinal space. The transretinal ERG (TR-ERG) was recorded from the detached retina between a pair of double-barreled microelectrodes of which the longer tip was positioned into the subretinal space, penetrating the detached retina and the shorter tip in the vitreous body. The vitreal ERG (VERG) from the undetached retina was simultaneously recorded between the shorter tip and a scleral electrode. The amplitude of the TR-ERG b-wave significantly decreased 2 hours after the onset of the detachment, and was gradually reduced to minimal value until 96 hours after the detachment. The amplitude of the VERG b-wave remained unchanged. The slow P III amplitude of the TR-ERG gradually decreased and extinguished 96 hours after the detachment, while the c-wave amplitude of the VERG showed no significant changes. The results suggested that the viability of the detached retina reduces rapidly and extinguishes within 96 hours in the rabbit eye. PMID- 1621609 TI - [Changing glucose concentration affects rod-mediated response in the perfused cat eye]. AB - The effects of changing glucose concentration on the ERG b-wave and optic nerve response (ONR) were studied in dark adapted, arterially perfused cat eyes. Changes in glucose concentration in the perfusate induced remarkable effects on both electrical responses. The ERG b-wave and ONR amplitudes were enhanced with increasing the glucose concentration above the standard level (5.5 mM), and were transiently decreased below the control after termination of the increase in glucose. Furthermore, a control perfusate with higher glucose concentrations (8 10 mM) was used, transient addition of glucose failed to elicit consistent increase in amplitudes of the b-wave and ONR. We conclude that the optimal supply of glucose to the mammalian retina is crucial for recording b-wave and ONR in vitro under dark adaptation. A higher glucose level (8-10 mM) than 5.5 mM in the standard tissue culture medium is suggested for maintaining the retinal function in-vitro. PMID- 1621610 TI - [Conductivity of sodium hyaluronate solution]. AB - In order to elucidate the property of water contained by the stereoic network in the vitreous gel, the conductivity of sodium hyaluronate solutions was measured in various concentrations at 25 degrees C and the relationship between concentrations of sodium hyaluronate and conductivity was evaluated. Each conductivity curve was divided into three stages. Equivalent conductivity was highly dependent upon the concentration of sodium hyaluronate at high and low concentrations, but was rather independent of it in intermediate concentrations. These results suggest that there are three types of water dependent upon the concentration of sodium hyaluronate, indicating physical variety, and that sodium hyaluronate solution in the intermediate concentration may possibly have a buffer homeostatic action on the ionic environment in the vitreous body. PMID- 1621611 TI - [A pupillographical study on the effects of cataract surgery on the contralateral eye]. AB - In order to estimate the effect of cataract surgery on the contralateral eye, we examined pupillary light reflex and performed laser flare-cell measurement. The subjects were nine patients who underwent extracapsular cataract extraction (ECCE) and fourteen patients who underwent ECCE with intraocular lens implantation. Pupillary light reflexes of the contralateral eyes were examined using a computerized videopupillogram (HTV C-301). Aqueous cells and flare of both eyes were measured by a laser flare-cell meter (KOWA FC 100). The author performed five successive measurements before and 1, 3 days, 1, 2 weeks and 1, 2, 3 months after surgery and statistically estimated the consensual effect of cataract surgery. As a result of contralateral cataract surgery, pupils became significantly miotic from the first postoperative day for more than 3 months without any alteration of other parameters of light reflex. On the contrary aqueous cells and flare significantly raised from the first postoperative day and disappeared within 3 months. Consensual miosis was considered to be sensitive indicator of postoperative inflammation of cataract surgery as well as contralateral increase of aqueous cells and flare. PMID- 1621612 TI - [Presence of human epidermal growth factor (hEGF), basic fibroblast growth factor (bFGF) in human aqueous]. AB - Thirty-eight cataract eyes and 15 artificial aphakic or pseudophakic eyes were enrolled in this study to determine levels of human epidermal growth factor (hEGF) and basic fibroblast growth factor (bFGF) in human aqueous, using a radioimmunoassay. Neither hEGF nor bFGF were detected in either congenital cataract eyes or senile cataract eyes without any complication. In cases of senile cataract complicated with glaucoma and traumatic cataract, bFGF range from 0.4 to 0.8 ng/ml whereas hEGF was not detected. In cases of senile cataract with myocardial or brain infarction and anterior subcapsular cataract, bFGF was detected ranging from 0.4 to 1.0 ng/ml and in some of the cases hEGF was detected at a level of 1.0 ng/ml. hEGF was detected at 1.0 ng/ml in some cases of secondary cataract after uveitis, cataract complicated with retinal detachment, cataract after scleral buckling or vitrectomy, and aphakic or pseudophakic eyes after extracapsular cataract extraction or phacoemulsification. These results showed that hEGF and bFGF exist at a level of about 1 ng/ml in human aqueous in some pathological states and it seems possible that proliferation of lens epithelial cells is promoted by the growth factors, with the result that after cataract, anterior capsular opacities and shrinkage become severe. PMID- 1621613 TI - [Effects of aging on fluorescein iris and angle photography in normal subjects]. AB - In the present study we took the fluorescein iris and angle photography of normal eyes and studied them according to different age groups. The range of age in 108 eyes of 92 subjects was from 20 to 93 years. They were free from any systemic diseases or ophthalmic diseases which would cause iris rubeosis. Fluorography was carried out using a Mizuno Trabeculens to determine the leakage points of fluorescence from the iris and the angle. In the angle there were gonio vessels which revealed no leakage of fluorescein. They were observed in 8 of 30 eyes (27%) for subjects in the fifth decade of life or less and in 24 of 78 eyes (31%) for subjects aged 50-90. No significant difference was seen between the two age groups. As to variations of gonio vessels, radial ciliary body vessel was found in 23 eyes, radial iris vessel or trabecular vessel in 10 eyes, and circular ciliary band vessel in 7 eyes. In the pupillary margin no leakage was seen in 30 eyes of 30 cases in the fifth decade of life or less, while leakage was found in 33 of 78 eyes, 42 of 62 cases over the fifth decade of life. In the angle leakage was seen in 4 of 30 eyes, 13 of 30 cases in the fifth decade of life or less, while leakage was observed in 43 of 78 eyes over the fifth decade of life. These results suggested that leakage of fluorescence from the pupillary margin, the angle or both increases with age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621614 TI - [In vivo observation of crystalline lens changes in the early post-vitrectomy stage]. AB - Crystalline lens changes of 17 cases of eye undergoing simple vitrectomy were observed from the post-operative 1st to 21st month. Changes in the crystalline lenses were detected through a slitlamp microscope or by methods of image analysis, the Opacity Lensmeter and the laser scattering spectroscopy. Increases of the scattering light intensity of the anterior and posterior deep cortical layers were observed from the early post-operative stage in 9 cases. Seven cases progressed to nuclear opacification during the observation period, however, one case showed no nuclear changes even at the 12 post-operative month. No relationships were observed between the early cortical changes and surgical invasion, patient age, or cause of vitreous opacification. Quantitative evaluation by image analysis revealed early post-operative crystalline lens changes in cases undergoing vitreous surgery. PMID- 1621615 TI - [Retinal circulation and ocular blood barrier in diabetic retinopathy]. AB - Macular capillary blood flow velocity, the score of fluorescein angiography in posterior region and aqueous flare intensity were investigated in 38 diabetics (41 eyes) and 6 normal subjects (6 eyes) to clarify the relationship among retinal circulation, blood-retinal barrier and blood-aqueous barrier. Macular capillary blood flow velocity was measured by means of the blue field entoptic phenomenon, the score of fluorescein angiography was graded by the extent of edema in the posterior region, aqueous flare intensity was measured with a flare cell meter. The results showed that the reduction of macular capillary blood flow is significantly associated with an increase in fluorescein angiography score and aqueous flare intensity via diabetic retinopathy (p less than 0.01). PMID- 1621616 TI - [De novo retinal break associated with excessive cryotherapy]. AB - Three patients who had been treated with transscleral cryotherapy for retinal breaks and associated retinal detachment developed de novo retinal breaks and/or retinal thinning at the site of cryotherapy in the early postoperative period. Additional surgical interventions were required because retinal detachment had extended or remained unchanged postoperatively. We think that this may be due to excessive cryotherapy and is an early postoperative complication transscleral cryotherapy that to our knowledge has not previously been reported. This would suggest that when performing cryotherapy for retinal breaks and associated retinal detachment, care should be taken not to treat excessively. PMID- 1621617 TI - 'The tort system is the problem'. PMID- 1621618 TI - A procedure to assist impaired colleagues. PMID- 1621619 TI - Our great heritage. PMID- 1621620 TI - Life after medicine. PMID- 1621621 TI - Fitness and Healthy Alabama 2000 health objectives. PMID- 1621622 TI - Addressing Alabama advocacy for the impaired physician. PMID- 1621623 TI - Under pressure. Soaring costs in health care will require some tough decisions. PMID- 1621624 TI - Diary from a week in practice. PMID- 1621625 TI - Responses to questions about family practice as a career. PMID- 1621626 TI - Temporomandibular joint disorder. AB - Temporomandibular joint disorder is a common clinical entity with diverse etiologies and symptoms. The hallmarks on physical examination are reduced or dysfunctional mandibular range of motion, malocclusion, and joint or preauricular tenderness. The diagnosis is made when a history of craniofacial symptoms or headache is linked with temporomandibular joint dysfunction. Temporomandibular joint disorders usually respond to medical treatment with anti-inflammatory medications, soft diet and occlusal therapy, without the need for surgical intervention. These disorders must be considered in the differential diagnosis of chronic headache, facial pain and compromised mandibular movement. PMID- 1621627 TI - Managing tricyclic antidepressant overdose. AB - Tricyclic antidepressant overdose is the most common cause of death from prescription drugs. Clinical presentation of overdose from the tricyclic agents includes cardiac arrhythmias, hypotension, seizures, coma and anticholinergic signs such as hyperthermia, flushing and intestinal ileus. The highly toxic/lethal level (greater than 1,000 ng per mL) is manifested on electrocardiograms as prolongation of the QRS interval to 100 milliseconds or more. Treatment includes establishment of an airway, proper oxygenation and ventilation, fluid replacement at maintenance levels, cardiac monitoring, gastric lavage and charcoal administration, alkalinization to a blood pH of 7.5 with intravenous sodium bicarbonate, supportive therapy and continued cardiac monitoring after clinical recovery. PMID- 1621628 TI - Common skin tumors in the elderly. AB - Skin tumors can have an epidermal, melanocytic or mesodermal origin. Lesions frequently encountered in elderly patients include benign tumors such as seborrheic keratoses, lentigo, keratoacanthoma, epidermal cyst and sebaceous hyperplasia. Premalignant and malignant tumors that often occur in the elderly include actinic keratosis, Bowen's disease, basal cell carcinoma, squamous cell carcinoma and melanoma. Diagnosis depends on the tumor's characteristics and morphology, although in some cases biopsy is required. Treatment depends on the character of the lesion, its location and the patient's general condition and includes curettage, cryosurgery, chemosurgery, excision and radiotherapy. PMID- 1621629 TI - Pectus excavatum. AB - Pectus excavatum is a congenital chest wall defect that can cause a marked cosmetic defect with attendant psychologic trauma and limitations of peak physical performance. Close observation of pectus excavatum is indicated, because this condition may improve or even disappear without treatment in some patients. However, in appropriate patients, timely surgical repair can give good cosmetic results and improve cardiorespiratory function, providing both physical and psychologic benefits. PMID- 1621631 TI - Recognition of retropharyngeal abscess in children. AB - Retropharyngeal abscess is a rare deep-neck infection that usually affects young children. Swelling in the neck can lead to sudden and fatal airway obstruction. Enlargement of lymph nodes located between the posterior pharyngeal wall and the prevertebral fascia occurs secondary to infection of the nasopharynx, paranasal sinuses or middle ear. Penetrating trauma or foreign-body penetration may also lead to abscess formation. Common symptoms include fever, swollen neck, difficult swallowing, muffled voice and hyperextension of the head and neck. Lateral neck radiographs confirm the diagnosis. Early surgical treatment prevents serious complications, such as mediastinal spread, aspiration of pus, airway obstruction or erosion into a major vessel. PMID- 1621630 TI - Methemoglobinemia: nitrate toxicity in rural America. AB - Nitrates are frequently found in vegetables and ground water. Nitrate levels in ground water have increased over the past two decades because of the heightened use of nitrogenous fertilizers. Following ingestion, nitrates are converted to nitrites by fecal organisms. Nitrites are absorbed and form methemoglobin, which interferes with the oxygen-carrying capacity of hemoglobin. Infants are particularly susceptible to nitrate poisoning because fetal hemoglobin is more readily oxidized to methemoglobin. In infants, the most common source of nitrate exposure is well water, which is mixed with infant formula. Affected infants may present with asymptomatic cyanosis, which can progress to dyspnea and lethargy or coma. Blood methemoglobin concentrations are elevated. Treatment consists of the administration of oxygen and intravenous and oral methylene blue. PMID- 1621632 TI - Human ehrlichiosis: a newly recognized tick-borne disease. AB - Human ehrlichiosis was first described in the United States in 1986. Since then, more than 215 cases have been reported, including some fatalities. Ehrlichia species belong to the same family as the organism that causes Rocky Mountain spotted fever. Human ehrlichiosis occurs most frequently in the southern mid Atlantic and south-central states, during spring and summer months. The clinical presentation is similar to that seen in Rocky Mountain spotted fever although, with ehrlichiosis, leukopenia is more often found and skin rash is less often noted. Definitive diagnosis is based on acute and convalescent serum antibody titers. Ehrlichiosis cannot reliably be distinguished from other common febrile illnesses on the basis of clinical, epidemiologic or laboratory features. Therapy must be initiated empirically in suspected cases. Both ehrlichiosis and Rocky Mountain spotted fever respond well to tetracycline and chloramphenicol, but not to penicillins or cephalosporins. PMID- 1621633 TI - Peptic ulcer disease. AB - Peptic ulcer disease affects between 5 percent and 10 percent of Americans during their lifetime. There are a variety of predisposing factors, including nonsteroidal anti-inflammatory drug (NSAID) use, Helicobacter pylori infection, tobacco use and, possibly, certain dietary practices. While H2-receptor antagonists remain the mainstay of therapy, the selection of an antiulcer drug should be individualized. Famotidine is preferred in persons who use alcohol, sucralfate may be preferred for maintenance therapy in smokers and omeprazole is useful in hypersecretors of acid and in patients with resistant ulcers. Antacids remain an effective treatment for uncomplicated duodenal ulcer in motivated patients. Eradication of H. pylori using a bismuth preparation plus one or two antibiotic agents should be considered in patients who have frequent recurrences and evidence of infection. Finally, risk factors such as tobacco or NSAID use should be modified whenever possible to reduce the risk of ulcer recurrence. PMID- 1621634 TI - Surfactant: clinical applications. AB - Pulmonary surfactant is an important chemical component of the lung. It decreases surface tension in the alveolar cells to help stabilize the alveoli, and it may help prevent pulmonary edema. Currently, naturally and synthetically derived surfactants are being used to treat neonatal respiratory distress syndrome, a leading cause of death in premature infants. Surfactant is recommended for prophylactic therapy in infants weighing less than 1,350 g (3 lb) and in infants weighing more than 1,350 g who show signs of pulmonary immaturity and for rescue therapy in infants with respiratory distress syndrome. Surfactant is administered by endotracheal tube, and the recommended dose is 5 mg per kg. Three doses, given 12 hours apart, is the recommended regimen for prophylactic therapy. Rescue therapy consists of one dose of surfactant given at the onset of respiratory distress and another dose given 12 hours later. PMID- 1621635 TI - ACIP issues statement on acellular pertussis vaccine. PMID- 1621636 TI - Low-dose interferon alpha and HIV infection. PMID- 1621637 TI - Adolescent sexuality. PMID- 1621638 TI - LDH as a marker for P. carinii pneumonia. PMID- 1621639 TI - Questions about family practice. PMID- 1621640 TI - AHCPR clinical practice guidelines. PMID- 1621641 TI - Monitoring physician use of new CPT codes by Medicare. PMID- 1621642 TI - Violence: a public health problem. PMID- 1621643 TI - An act of faith. PMID- 1621644 TI - Responding to tragedy in Evansville, Indiana. PMID- 1621645 TI - Mechanical rotational atherectomy. AB - Percutaneous transluminal coronary angioplasty (PTCA) is practiced widely in the United States and is indicated for the majority of stenosed vessels that have de novo, type A lesions. Despite extensive experience with the procedure and improvements in balloon technology, periprocedural dissection and restenosis remain major limitations of PTCA. Research indicates that certain lesion types and patient populations may be treated more effectively with other technologies. New mechanical devices have been designed to help improve the safety of PTCA and hold promise for correcting coronary dissection and abrupt closure--the sources of such angioplasty complications as myocardial infarction, urgent bypass surgery, and death. Among the results achieved with the new atherectomy techniques are a more stable lumen after atherectomy; a decrease in elastic recoil; a smoother, less thrombogenic lumen; and the feasibility of extensive debulking or endarterectomy. Experience indicates that mechanical rotational atherectomy will be an extremely useful addition to the armamentarium for percutaneous revascularization. PMID- 1621646 TI - Cardiopulmonary support. AB - Cardiopulmonary support (CPS) has been shown to be a useful addition to interventional cardiology when considering alternatives for high-risk patients. Cardiopulmonary support systems are capable of up to 6 liters/min output and can be used prophylactically to prevent hemodynamic collapse following balloon occlusions or acute vessel closure. The technique, supported angioplasty, results in reductions of preload and afterload and allows prolonged balloon inflations in critical coronary vessels. Although it provides excellent support for most high risk patients, CPS is a technically challenging and expensive procedure associated with significant patient morbidity. Standby CPS patients are prepared for institution of CPS, but bypass is not actually initiated unless the patient sustains irreversible hemodynamic compromise. In this study, standby and prophylactic patients had comparable success and major complication rates, but procedural morbidity was more frequent in prophylactic patients. Further study will better define appropriate patient selection for standby versus prophylactic CPS. PMID- 1621647 TI - Complex angioplasty: a surgeon's perspective. AB - Surgeons commonly have reacted with skepticism to the introduction of catheter based interventional approaches to treating coronary artery disease, prompted apparently, by a desire to protect what had been exclusively their turf. Reasonable surgeons now largely accept the concept of nonoperative mechanical treatment of coronary heart disease, and their constructive criticisms regarding amelioration of coronary anatomy without thoracotomy remains valuable. The value of catheter-based techniques compared with operative or noninterventional treatment has not been defined in many clinical settings. The complexity of evaluating these rival technologies increases as the complexity of cases progresses from simple 1-vessel disease to more extensive coronary artery disease. Ongoing randomized trials may help define indications for these procedures, but patients entering these trials represent a highly select subset. Therefore, applications to broader patient populations will likely require analysis of observational data. Newer catheter-based technologies introduce modes of injury to the coronary arterial system that have not been encountered previously in medical practice. As technologies evolve, decisions about the need for operative intervention become increasingly complex. In the many clinical settings resulting from efforts to improve angioplasty, optimal patient care occurs in environments with good communication and cooperation between all physicians involved in interventional treatment of coronary artery disease. PMID- 1621648 TI - Changing trends for surgical standby in patients undergoing percutaneous transluminal coronary angioplasty. AB - In 1988 the American College of Cardiology/American Heart Association (ACC/AHA) task force subcommittee on Guidelines for Percutaneous Transluminal Coronary Angioplasty (PTCA) recommended that an experienced cardiovascular surgical team be available within the institution for emergency surgery for all angioplasty procedures. The subcommittee felt strongly that this requirement allowed for no exception, stating that it could not condone existing arrangements that required the transportation of patients to off-site surgical facilities for emergency cardiac surgery. Such arrangements failed to meet the necessary standards of care exercised by prudent physicians. Interventional cardiologists are recognizing that it may be prudent for the ACC/AHA task force to revise its 1988 guidelines. Improved operator technique and new technologic advances, such as lasers, atherectomy devices, stents, and perfusion pumps and balloons, have helped extend the reach of PTCA to more seriously ill patients. With new technologies for angioplasty and an increased awareness of risk factors, active standby can be markedly reduced, thereby resulting in enormous cost reductions and in more appropriate patient care. PMID- 1621649 TI - Excimer laser coronary angioplasty. AB - Recent experience with excimer laser coronary angioplasty (ELCA) has shown the safety and efficacy of the technique in the treatment of coronary stenosis, with results similar to percutaneous transluminal coronary angioplasty (PTCA). Several advantages of the excimer laser for intravascular use have been identified by the ELCA Registry, a group of 15 institutions nationally that have pooled data on their cooperative experience with ELCA. Advantages include the ability of the laser to ablate atheroma with microscopic precision without thermal injury and the ability of vessel surfaces to heal without scarring. The initial results of the multicenter investigation of ELCA in 958 patients indicate that ELCA may be indicated particularly for long, diffuse lesions. With the advent of larger diameter catheters, ELCA is a viable alternative to PTCA. Restenosis was seen as a significant problem, and it remained problematic at 6-month follow-up. In comparison with conventional balloon angioplasty, ELCA may eliminate that component of restenosis due to inadequate dilation or elastic recoil, but it does not appear to affect restenosis caused by smooth muscle proliferation. Catheter design and energy delivery continue to evolve and may affect future results of laser coronary angioplasty. PMID- 1621650 TI - FNA identification of familial breast disease. PMID- 1621651 TI - A second look at breast-feeding and full-time maternal employment. PMID- 1621652 TI - Fluid management and arginine vasopressin in bacterial meningitis. PMID- 1621653 TI - Working hours for pediatric residents. PMID- 1621654 TI - The role of general pediatrics in an academic department. PMID- 1621655 TI - Safety and immunogenicity of high-dose Edmonston-Zagreb measles vaccine in children with HIV-1 infection. A cohort study in Kigali, Rwanda. AB - OBJECTIVE: To compare the reactogenicity and immunogenicity of high-dose Edmonston-Zagreb (EZ) measles vaccine in children with and without human immunodeficiency virus, type 1 (HIV-1), infection. DESIGN: Prospective cohort study. SETTING: General pediatric clinic and home visits in Kigali, the capital of Rwanda. PARTICIPANTS: Infants born to HIV-1-seropositive and -seronegative mothers were vaccinated with a 10(5.0) 50% tissue culture infective dose of EZ measles vaccine at 6 months of age. Control visits were made 10 and 14 days later to monitor local and general reactions. Measles serum antibodies were measured by an enzyme-linked immunosorbent assay technique at birth and at 6 and 9 months of age. Three groups were compared: infected children (n = 43), uninfected children born to seropositive mothers (n = 135), and uninfected children born to seronegative mothers (n = 194). RESULTS: Three hundred twenty-three children (86.8%) were available for the reactogenicity study. No statistically significant difference between the three groups was found in the occurrence of minor adverse reactions. No severe adverse reaction was observed. One hundred ninety children (51.1%) were available for the immunogenicity study. The percentage of infants negative for measles antibody at 6 months was significantly higher (P = .021) in HIV-infected children (85%) and in uninfected children born to seropositive mothers (90%) than in uninfected children born to seronegative mothers (75%). The overall seroconversion rate at 9 months was 90% (95% confidence interval, 85.7% to 94.3%), without any statistically significant difference between the three groups. CONCLUSION: High-dose EZ vaccine administered at 6 months of age is safe and highly immunogenic in both HIV-infected and uninfected children. PMID- 1621656 TI - Clinical reactions and immunogenicity of the BIKEN acellular diphtheria and tetanus toxoids and pertussis vaccine in 4- through 6-year-old US children. AB - OBJECTIVE--To compare the immunogenicity and reactogenicity of a two-component acellular pertussis vaccine with a whole-cell diphtheria and tetanus toxoids and pertussis vaccine (W-DTP) when administered as a booster to children 4 through 6 years of age. DESIGN--This was a randomized, double-blind study. SETTING- Children in this study were from three general pediatric practices (two were private, one was university-affiliated). PARTICIPANTS--Three hundred and sixteen 4- through 6-year-old children who had received four previous W-DTP immunizations at the recommended times were studied. SELECTION PROCEDURES AND INTERVENTIONS- Children were randomly assigned in a 1:3 ratio to receive either W-DTP or one of three lots of acellular diphtheria and tetanus toxoids and pertussis vaccine (A DTP). The A-DTPs contained 3.75 micrograms each of lymphocytosis promoting factor and filamentous hemagglutinin protein nitrogen per 0.5 mL and the same concentrations of diphtheria and tetanus toxoids as W-DTP. Serum samples were obtained on the day of immunization and 4 to 6 weeks later. Adverse reactions were recorded by parents at 6, 24, 48, and 72 hours. MEASUREMENTS AND RESULTS--An indirect enzyme-linked immunosorbent assay (ELISA) method determined IgG antibody response to lymphocytosis promoting factor, filamentous hemagglutinin, and tetanus toxoid; a CHO cell assay measured neutralizing antibodies to pertussis toxin; and serum neutralization on VERO cells assayed diphtheria antitoxin. One month after booster doses were administered, the geometric mean antibody levels for A-DTP vs W-DTP were IgG filamentous hemagglutinin, 362 vs 104 ELISA U/mL; IgG lymphocytosis promoting factor, 408 vs 81 ELISA U/mL; CHO cell, 210 vs 107; diphtheria, 21.7 vs 12.1 U/mL; and tetanus, 2.86 vs 2.04 Eq/mL. Following immunization with A-DTP, local and systemic adverse experiences were 30% to 50% and 20% to 30% fewer, respectively, as compared with W-DTP. CONCLUSIONS--The BIKEN A-DTP vaccine used in this study demonstrates enhanced immunogenicity to lymphocytosis promoting factor, filamentous hemagglutinin, and other measured antigens and less reactogenicity compared with licensed W-DTP [corrected]. PMID- 1621657 TI - Severity and frequency of sequelae of bacterial meningitis in Alaska Native infants. Correlation with a scoring system for severity of sequelae. AB - OBJECTIVES: To (1) determine the frequency and severity of sequelae of Haemophilus influenzae type b and Streptococcus pneumoniae meningitis in Alaska Native children, (2) compare morbidity and mortality of H influenzae b and S pneumoniae meningitis, and (3) evaluate the applicability of the Herson-Todd prognostic score (HTPS) to both H influenzae b and S pneumoniae meningitis in this population. DESIGN: A retrospective study of all cases of H influenzae b and S pneumoniae meningitis in Alaska Native children younger than age 5 years. Data on meningitis sequelae, obtained from medical charts and records of the Infant Learning Program, were collected, and incidence of sequelae tabulated. Data obtained on admission to the hospital were used to calculate HTPS. SETTING: Indian Health Service facility for the Yukon-Kuskokwin Delta region of southwest Alaska. STUDY SUBJECTS: 51 of 63 Alaska Native children with H influenzae b meningitis and 13 of the same 63 Alaska Native children with S pneumoniae meningitis occurring between 1980 and 1988. One child was infected with both organisms, producing a total of 64 cases for study. SELECTION PROCEDURES: Cases were identified by surveillance for these diseases between January 1, 1980, and December 31, 1988, maintained by the Arctic Investigations Program, Centers for Disease Control. MEASUREMENTS AND RESULTS: Sequelae of bacterial meningitis caused by H influenzae b were equal to or exceeded rates of sequelae described in other children in the United States. After H influenzae b meningitis, motor abnormalities (29%) and hydrocephalus (7%) occurred two to four times more often in Alaska Native children than in children in other parts of the United States. Differences in severity of H influenzae b sequelae could not be accounted for by microbiologic markers of the H influenzae b strain, including ampicillin sensitivity, biotype, outer membrane protein type, or electropherotype. Numbers of cases of S pneumoniae meningitis were too small for statistically valid comparison, but sequelae of S pneumoniae meningitis occurred in roughly equal proportion as sequelae of H influenzae b meningitis. The HTPS was applied to Alaska Native children with H influenzae b meningitis and was found to be very accurate in predicting children with major sequelae. Analysis of the prognostic factors used in deriving the HTPS revealed a unique set of predictors for sequelae in Alaska Native children: seizures at admission, glucose levels in cerebrospinal fluid of less than 1.1 mmol/L; and male gender, with a significant predictive interaction between male gender and age less than 6 months at admission. CONCLUSIONS: Alaska Native children suffer greater neurologic morbidity as a result of H influenzae b meningitis than do their non-Native counterparts. The HTPS was a good predictor of major sequelae in Alaska Native children with H influenzae b or S pneumoniae meningitis and could be useful in determining which patients need referral to a tertiary care center. PMID- 1621658 TI - Long-term outcome of neonatal meningitis. AB - OBJECTIVE: To determine the long-term outcome of neonatal bacterial meningitis and the relationship between the outcome and specific features in the acute stage of the disease; and to compare the outcome between infants with neonatal meningitis and high-risk infants without meningitis. DESIGN: Prospective clinical evaluations of 21 survivors of meningitis and 21 matched controls who were retrospectively selected from a high-risk patient population. SETTING: Program of follow-up performed at the Children and Youth Project's High Risk Center of the Department of Pediatrics, University of Louisville, Louisville, Ky. Neonates were inborn at a university hospital with a high-risk obstetric unit and level III nursery. PATIENTS: Twenty-six consecutive neonates born between 1970 and 1980 with culture-proven bacterial meningitis, excluding neonates with congenital neurologic defects. Nineteen of 21 survivors and 21 controls matched by age, sex, race, birth weight, and gestational age were followed up from 1 to 14 years (mean, 7.8 years). Both survivors and controls fell below the federal poverty guidelines. RESULTS: Gram-positive meningitis was twice as common as gram negative meningitis with co-occurrence of meningitis and sepsis in half of the cases. Neonates with gram-positive meningitis and higher birth weight had a higher survival rate, but this finding was not statistically significant. The mortality rate in neonates with gram-negative meningitis was almost three times higher than that of neonates with gram-positive meningitis, but no significant difference was observed between their morbidity rates. Eight (38%) of 21 survivors were normal, while another eight (38%) and five (24%) had mild and moderate to severe sequelae, respectively. Survivors of meningitis had lower IQ scores and more severe sequelae than matched controls. CONCLUSION: Neonatal bacterial meningitis results in poorer long-term outcome than in controls, but improved outcome compared with previous studies of neonatal meningitis. PMID- 1621659 TI - Factors influencing the choice of a residency training program. A student's perspective. AB - Current trends in pediatric residency training have shown that a growing number of programs have been unable to fill their available positions through the National Resident Matching Program, Evanston, Ill. This has caused a competitive climate among programs to attract medical students as potential residents. The purpose of this study was to learn what factors are important to all students in determining the rank order of the residency training programs to which they have applied. Analysis of data obtained from 600 survey respondents (40%) showed that program curriculum was most important. Factors, such as night call and benefits, took on much less importance. Differences did exist between students who applied for pediatric vs other residencies. The balance between primary and tertiary care and a university setting are examples of variables that had a greater influence on aspiring pediatricians. This information has important implications for training program directors. PMID- 1621660 TI - Effect of somatotropin of mammalian cell origin in growth hormone deficiency. AB - Sixty-nine growth hormone-deficient patients were treated for 1 year with somatotropin (recombinant DNA-derived human growth hormone) produced in mouse cells. The growth velocity of the 50 patients (72%) in whom the effectiveness of this growth hormone could be evaluated increased from a mean (+/- SD) of 3.5 +/- 1.1 to 8.7 +/- 1.6. cm/y. An enhanced rate of weight gain was also observed. Bone age was not unduly accelerated. One of 66 patients developed antibodies to recombinant growth hormone, which did not affect the response to therapy. No patient developed antibodies to host cell proteins. An increased insulin response to a standard glucose load, without any change in glucose tolerance, was observed after 1 year of treatment. This authentic sequence human growth hormone preparation produced in mammalian cells is both effective and safe in the treatment of children with growth hormone deficiency. PMID- 1621661 TI - Calcium and zinc retention from protein hydrolysate formulas in suckling rhesus monkeys. AB - OBJECTIVE: To determine calcium and zinc retention from infant formulas based on protein hydrolysates. DESIGN: Randomized, crossover. SETTING: Newborn nursery at the California Primate Research Center, Davis. PARTICIPANTS: Suckling infant rhesus monkeys (N = 7), aged 6 weeks at the beginning of the study. Each infant received seven different formulas. INTERVENTIONS: Fasted infant monkeys were fed diets radiolabeled with calcium 47 and zinc 65. Retention was determined by counting whole body radioactivity immediately after dosing and 7 days after dosing. MEASUREMENTS AND RESULTS: Retention of 47Ca was a mean (+/- SEM) of 79% +/- 4% from casein hydrolysate and 72% +/- 6% from the whey protein hydrolysate formula. Calcium 47 retention from hydrolysates based on whey protein/casein mixtures (a ratio of 60:40 or 50:50) was similar despite differences in protein sources and calcium content. Calcium 47 retention from two types of soy/collagen hydrolysate formula was found to be 68% +/- 6% and 59% +/- 4%, respectively, which is significantly lower than retention from casein hydrolysate. Considering the different calcium content of these formulas, total calcium retention from milk protein hydrolysates was higher than from soy/collagen products. Retention of 65Zn from milk protein hydrolysates ranged from 18% +/- 3% to 29% +/- 4% and was higher than that from soy/collagen formulas with a mean retention of 7% +/- 3% and 10% +/- 4%, respectively. Despite these differences in 65Zn retention, total zinc retention from all soy/collagen formulas was similar due to their higher zinc content. CONCLUSIONS: Calcium and zinc bioavailability was high from formulas based on milk protein hydrolysate, but was considerably lower from soy hydrolysates. Higher levels of calcium and zinc provided in soy hydrolysate formula compensated for the lower bioavailability and resulted in similar amounts of calcium and zinc retained. PMID- 1621662 TI - Male pseudohermaphroditism resulting from 17 alpha-monooxygenase (P-450C17) deficiency in two unrelated Guamanians. AB - OBJECTIVE: To report the cases of and to describe two unrelated Guamanian patients with an unusual form of congenital adrenal hyperplasia resulting from 17 alpha-monooxygenase deficiency (P-450C17). DESIGN: Patient series. SETTING: Referral center. PATIENTS: Two phenotypic females of Guamanian descent, unrelated, and referred for evaluation of hypertension and delayed sexual development. INTERVENTIONS: Diagnosis by measurement of specific adrenocortical precursors and initiation of therapy with dexamethasone. Documentation of response by decrease in circulating concentrations of metabolites and decrease in blood pressure. CONCLUSIONS: The finding of a rare autosomal recessive disorder in two unrelated persons from a small genetic pool in Guam suggests that this may result from the same molecular defect and may be present in this population at an unexpectedly high incidence. Lack of suspicion frequently leads to unnecessary delay in diagnosis of this condition. PMID- 1621663 TI - The pediatrician's documentation of child maltreatment. AB - Pediatricians are increasingly involved in the assessment of suspected child maltreatment. These assessments are a crucial component of the overall evaluation of the patient and provide the basis for interventions to protect the child. An accurate documentation of the pediatrician's assessment is important to convey the information to professionals in the public agencies involved, including the legal system. However, there may be uncertainty among pediatricians concerning what should be documented in the medical record in cases of child maltreatment. The objectives of this article are to provide a detailed but generic description of the information that should be gathered during the evaluation of children who show signs of any form of child abuse and neglect and to provide clear guidelines for the proper written documentation of child maltreatment. PMID- 1621664 TI - Lacerations involving glass. The role of routine roentgenograms. AB - OBJECTIVE: To determine, when evaluating a laceration caused by glass, whether seeing that the bottom of the wound is free of glass eliminates the possibility that glass is present in the wound. RESEARCH DESIGN: Prospective patient series. SETTING: Two pediatric emergency departments. PARTICIPANTS: 226 children with lacerations due to glass occurring in a period of 21 months. SELECTION PROCEDURES: Consecutive sample. INTERVENTIONS: Before obtaining a roentgenogram, the triage nurse or the managing physician visually inspected each wound and recorded whether the bottom of the wound was seen, if glass was seen in the wound, and the length and depth of the wound. Further treatment of the wound was at the discretion of the managing physician. MEASUREMENTS/MAIN RESULTS: Glass was seen in the wounds of 10 children on initial inspection. Of the remaining 216 injuries, glass was contained in 12 (21.4%) of the 56 lacerations when the bottom of the wound was not visualized, and in 11 (6.9%) of the 160 lacerations when the bottom of the wound was visualized. There was a significant association between the depth of the wound and an inability to see the bottom of the wound, and deeper wounds were significantly more likely to contain glass. All but one of the lacerations containing glass had a depth of at least 0.5 cm. CONCLUSIONS: In the population studied, seeing that the bottom of the laceration was free of glass reduced, but did not eliminate, the possibility that glass was present in the wound. In addition, superficial lacerations (less than 0.5 cm) rarely contained undetected glass fragments. We recommended that further investigation concerning the mechanism of injury, the depth of the wound, and the type of glass involved is needed before physicians abandon routine roentgenography for lacerations due to glass. PMID- 1621665 TI - The physical health of children in kinship care. AB - OBJECTIVE: The objectives of this study were to assess the current and chronic health problems and the adequacy of primary health care of children placed with a relative (kinship care) by a public agency. RESEARCH DESIGN: Population survey. SETTING: Children in kinship care in Baltimore, Md. PARTICIPANTS: Four hundred seven (78%) of 524 children in kinship care in 1989. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Information on the child's health status and care was obtained via a review of medical records; questionnaires sent to primary care physicians, parents, care givers, and caseworkers; and clinical assessment of the child by a nurse, pediatrician, and child psychologist. The children were found to have health problems similar to those in foster and poor children, but more problems than American children in general. Frequent diagnoses included impaired visual acuity and hearing, obesity, dental caries, and asthma; often, these problems had not been identified or treated. Gaps in the medical records precluded firm conclusions concerning the children's primary care, but suggest an inadequate system for ensuring their health care. CONCLUSIONS: There is a need for improving the system of health care for children in kinship care. There is also a need for additional research on this high-risk group of children. PMID- 1621666 TI - Equestrian injuries in children and young adults. AB - We reviewed the English language scientific literature about equestrian injuries among children and young adults. All studies showed that more females than males were injured, with falls from horses being the most common cause of injury. Fractures were common, and head injuries were associated with the vast majority of deaths (72% to 78%) and hospitalizations (55% to 100%). Although the overall injury rate was low, equestrian athletes are at risk for serious injuries. Pediatricians should know the medical contraindications for participation in equestrian sports and encourage riders to obtain horse safety training and use protective headgear (helmets) approved by the American Society for Testing Materials when riding or working around horses. Pediatricians can play an active role in increasing public awareness of equestrian injuries and in reducing risk of injury. PMID- 1621667 TI - School-based adolescent health care. Review of a clinical service. AB - OBJECTIVE: To provide recommendations regarding the establishment and maintenance of school-based clinics, based on analysis of data from a clinic located in a New York City high school. DESIGN: Review of demographic, medical, and psychosocial data collected during student visits. SUBJECTS: During 2 1/2 years, 1283 students were seen. The students were 53% girls and 47% boys; 65% black and 25% Hispanic; and 65% grades 9-10 and 35% grades 11-12. RESULTS: There were 7920 visits. Visits were for acute or chronic medical problems (44%), physical examinations and immunizations (25%), gynecologic or sexuality-related issues (17%), and mental health concerns (14%). Psychosocial characteristics of the 378 students who enrolled during the 1989-1990 academic year indicated that only 27% lived with both natural parents, 55% were foreign-born, 37% had repeated a grade at least once, 44% were sexually active, 13% drank alcohol, and 14% had past or present suicidal ideation. CONCLUSIONS: These data demonstrate that a school-based clinic can be involved in the management of a wide range of health care needs for large numbers of at-risk youth. In addition, school-based clinics can serve as a major site for the teaching of medical students and residents, and as a valuable resource for clinical research. PMID- 1621668 TI - Antipyretic efficacy of ibuprofen vs acetaminophen. AB - OBJECTIVE: To compare the antipyretic efficacy of ibuprofen, placebo, and acetaminophen. DESIGN: Double-dummy, double-blind, randomized, placebo-controlled trial. SETTING: Emergency department and inpatient units of a large, metropolitan, university-based, children's hospital in Michigan. PARTICIPANTS: 37 otherwise healthy children aged 2 to 12 years with acute, intercurrent, febrile illness. INTERVENTIONS: Each child was randomly assigned to receive a single dose of acetaminophen (10 mg/kg), ibuprofen (7.5 or 10 mg/kg), or placebo. MEASUREMENTS/MAIN RESULTS: Oral temperature was measured before dosing, 30 minutes after dosing, and hourly thereafter for 8 hours after the dose. Patients were monitored for adverse effects during the study and 24 hours after administration of the assigned drug. All three active treatments produced significant antipyresis compared with placebo. Ibuprofen provided greater temperature decrement and longer duration of antipyresis than acetaminophen when the two drugs were administered in approximately equal doses. No adverse effects were observed in any treatment group. CONCLUSION: Ibuprofen is a potent antipyretic agent and is a safe alternative for the selected febrile child who may benefit from antipyretic medication but who either cannot take or does not achieve satisfactory antipyresis with acetaminophen. PMID- 1621669 TI - Comparison of multidose ibuprofen and acetaminophen therapy in febrile children. AB - OBJECTIVE: To determine whether febrile children receiving 2.5-, 5-, or 10-mg/kg ibuprofen therapy via a liquid or 15-mg/kg acetaminophen therapy via an elixir every 6 hours for 24 to 48 hours show equivalent fever reduction or suffer adverse effects of the drug administered. DESIGN: Randomized, double-blind, multidose, parallel-group, variable-duration (24 to 48 hours) clinical trial. SETTING: The academically affiliated Children's Hospital in Columbus, Ohio. PARTICIPANTS: 64 febrile (defined as oral or rectal temperature of 39 degrees C to 40.5 degrees C) but otherwise healthy children aged 6 months to 11 years 7 months randomly assigned to one of the four drug regimens. INTERVENTIONS: Treatment with either ibuprofen or acetaminophen as described above. Administration of antibiotics or intravenous fluids was allowed only after at least 24 hours of treatment with the assigned drug. MEASUREMENTS/MAIN RESULTS: In 61 of the 64 evaluable patients, treatments were effective and well tolerated during the entire study. While the rates of temperature reduction and maximal reduction of fever after administration of the initial dose were equal for patients receiving 10-mg/kg ibuprofen therapy and 15-mg/kg acetaminophen therapy, and both regimens were more effective than smaller doses of ibuprofen in reducing fever, after the second dose (and continuing to the end of the study) there were no statistically significant differences in temperature response among the treatment groups. Six children were withdrawn from the study, two because of dosing errors, three because of hypothermia (temperature of less than 35.6 degrees C; all three patients were in the acetaminophen group), and one because of gastrointestinal distress (this child was in the group receiving 2.5-mg/kg ibuprofen therapy). No other significant symptoms or adverse laboratory or physical findings were noted. While further confirmatory studies are needed, ibuprofen liquid (10 mg/kg) and acetaminophen elixir (15 mg/kg) administered every 6 hours for 24 to 48 hours appeared to be most effective in reducing fever. These two regimens were equally effective and equally tolerated in febrile children. Lower ibuprofen doses (2.5 and 5 mg/kg) were less effective than acetaminophen and 10-mg/kg ibuprofen therapy after the initial dose but were at least equally effective as these two higher-dose regimens thereafter. PMID- 1621670 TI - Radiological case of the month. Pica. PMID- 1621671 TI - Radiological case of the month. Extensive neonatal subarachnoid hematoma. PMID- 1621672 TI - Picture of the month. Erythema marginatum in acute rheumatic fever. PMID- 1621673 TI - Pathological case of the month. Chronic granulomatous disease with histologic features of pulmonary sequestration. PMID- 1621674 TI - Tubulointerstitial changes as a major determinant in the progression of renal damage. AB - Tubulointerstitial injury is an invariant finding in the chronically diseased kidney, irrespective of the type of disease or the compartment in which the disease originates. Such histologic changes are functionally significant in that scores for such damage, rather than glomerular injury, correlate with decline of renal function. This review summarizes (1) clinical evidence attesting to tubulointerstitial changes as an index of functional impairment, (2) mechanisms by which tubulointerstitial injury impairs renal function, and (3) interactions of pathologic processes in the vascular, glomerular, tubular, and interstitial compartments that culminate in tubulointerstitial injury. This report concludes with a review of interstitial fibrosis, a pathologic process regarded as an irreversible outcome from tubulointerstitial injury. PMID- 1621675 TI - The Modification of Diet in Renal Disease Study: design, methods, and results from the feasibility study. AB - The Modification of Diet in Renal Disease (MDRD) Study is a multicenter clinical trial designed to assess acceptance, safety, and efficacy of restricted protein and phosphorus diets in patients with progressive renal disease. The Feasibility Study was designed to test procedures and recruitment strategies and to estimate sample size for the Full-Scale Trial. The Feasibility Study was not designed to compare rates of progression of renal disease among diet groups. Patients aged 18 to 75 years, with a glomerular filtration rate (GFR; measured by 125I-iothalamate clearance) between 7.5 and 80 mL/min/1.73 m2, and a previous progressive increase in serum creatinine, were eligible for enrollment. Compliance with prescribed dietary protein intake was calculated from urea nitrogen appearance (UNA). Nutritional status was monitored by anthropometry and serum proteins. Progression of renal disease was calculated as the rate of decline of GFR. Ninety-six patients met all of the eligibility requirements and were randomized to study diets. Follow-up was conducted for a mean duration of 14 months (range, 2 to 22 months). Although most patients did not achieve the prescribed protein intake, marked changes in intake were observed among patients assigned to the low-protein diets, and mean estimated protein intake differed significantly among diet groups. No patients became malnourished. Mean rates of decline in GFR were relatively slow, and variability among individuals was high. As expected, the number of patients enrolled was too small to determine if the rate of decline in GFR was significantly slower among patients assigned to the restricted protein and phosphorus diets. The rate of decline in GFR was significantly inversely correlated with long-term average mean arterial blood pressure (MAP), even among patients whose blood pressure was controlled to levels within the normal range. However, because patients were not randomly assigned blood pressure goals, it was not possible to determine whether a causal relationship exists. Based on the experience gained during the Feasibility Study, the design for the Full-Scale Study includes two studies of defined by patients' baseline levels of renal function. Within each study, patients will be assigned randomly to one of two diets, and within each diet group, to one of two levels of blood pressure control. Based on variability of rates of decline in GFR slopes observed during the Feasibility Study, 800 patients with follow-up periods of up to 4 years will be required for the Full-Scale Trial. PMID- 1621676 TI - Long-term follow-up and response to chemotherapy in patients with light-chain deposition disease. AB - Nineteen patients with light-chain deposition disease (LCDD) were studied retrospectively. This report presents data on long-term patient and renal survival and the response to intermittent administration of melphalan and prednisone. Immunoelectrophoresis or immunofixation demonstrated a monoclonal protein in the serum of 78% and in the urine of 84% of the patients; 16% had no demonstrable monoclonal protein in serum or urine. The median age at presentation was 51 years (range, 37 to 77 years). Twelve (63%) of the patients had a monoclonal protein of undetermined significance without evidence of myeloma. The typical glomerular lesion was a diffuse mesangial nodular lesion that was positive for periodic acid-Schiff (PAS) stain with acute and chronic tubulointerstitial changes. Fifteen patients had kappa light-chain deposition and four had lambda light-chain deposition. Five-year actuarial patient survival and survival free of end-stage renal disease were 70% and 37%, respectively. Seventeen patients received melphalan and prednisone, and one patient received chlorambucil and prednisone. All of the patients had some impairment of renal function at presentation, and 58% had a serum creatinine concentration greater than 354 mumol/L (4.0 mg/dL). There was either stabilization or improvement in renal function after chemotherapy in five of eight patients who had a serum creatinine concentration less than 354 mumol/L (4.0 mg/dL) at the initiation of therapy. Of the 11 patients with a high serum creatinine concentration (greater than 354 mumol/dL [4.0 mg/dL]), 82% progressed to end-stage renal disease despite therapy. Follow-up urine protein studies demonstrated at least a 50% decrease in urine protein excretion in five of 15 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621677 TI - Effects of ascorbic acid and pyridoxine supplementation on oxalate metabolism in peritoneal dialysis patients. AB - We studied the effect of vitamin C and B6 supplementation on oxalate metabolism in seven patients receiving chronic peritoneal dialysis therapy. The study was divided into three phases, each lasting 4 weeks. Plasma oxalate, total ascorbic acid, and pyridoxal-5'-phosphate (PLP) were measured at the end of each phase. Twenty-four-hour urinary excretion and dialysate removal rates of oxalate were also obtained. At the end of phase I (supplement-free period), plasma oxalate levels were markedly elevated at 47.6 +/- 7.1 mumol/L (437 +/- 66 micrograms/dL) (normal, 3.4 +/- 0.4 mumol/L [30.3 +/- 1.6 micrograms/dL]). Plasma total ascorbic acid levels were 62 +/- 6 mumol/L (1.0 +/- 0.1 mg/dL) (normal, 45 to 57 mumol/L [0.8 to 1.0 mg/dL]), while plasma PLP levels were markedly reduced to 24 +/- 5 nmol/L (normal, 40 to 80 nmol/L). Daily supplements of 0.57 mmol (100 mg) ascorbic acid orally (phase II) resulted in a 19% increase in the plasma oxalate levels to 57.8 +/- 6.1 mumol/L (520 +/- 55 micrograms/dL) (P less than 0.03), with a concomitant 60% increase in the plasma ascorbate levels (91 +/- 6 mumol/L [1.6 +/- 0.1 mg/dL], P less than 0.01). Plasma PLP values remained low. Finally, during phase III (0.57 mmol or 100 mg ascorbic acid plus 59.6 mumol or 10 mg pyridoxine HCI orally daily), plasma oxalate levels declined by 17% to 47.9 +/- 5.2 mumol/L (431 +/- 47 micrograms/dL) (P greater than 0.05 v phase II).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621678 TI - Modest reduction of serum albumin in continuous ambulatory peritoneal dialysis patients is common and of no apparent clinical consequence. AB - It is commonly assumed that a reduction in serum albumin is a reliable sign of nutritional inadequacy affecting prognosis in continuous ambulatory peritoneal dialysis (CAPD) patients. We studied prospectively 19 patients starting CAPD and monitored them for a minimum of 15 months. Serum albumin, changes in dry weight, morbid events, and, where possible, protein catabolic rates (PCR) and urea nitrogen appearance (UNA) were determined. A modest reduction in serum albumin (25 to 33 g/L [2.5 to 3.3 g/dL]) was found in the majority of patients 3 months after starting CAPD, which persisted for 12 months. Most of these patients gained weight and were not hospitalized in that period. PCR and UNA values showed adequate nutrition. Two patients developed serious medical problems leading to clinical malnutrition and serum albumin rapidly falling below 20 g/L. A modest reduction in serum albumin (25 to 33 g/L) is common in healthy CAPD patients and, if stable, does not indicate a poor prognosis or nutritional inadequacy. PMID- 1621679 TI - Patterns of low incidence of treated end-stage renal disease among the elderly. AB - We present US county-level maps of the 1983 to 1988 incidence of treated end stage renal disease (ESRD) among white and nonwhite persons 65 years of age and older (N = 66,129). Recent statistical advances permit the investigation of geographical patterns of unusually low disease incidence. Our maps highlight those US counties which have been determined to have rates of ESRD treatment incidence that are low relative to those of all counties, revealing several interesting geographic patterns. For whites, low rates are found in the Northwest, the Midwest, and the South. Nonwhite rates are seen to be low primarily in the South and Alaska. Low treatment incidence could be due to a combination of (1) low true incidence, (2) lack of access to health care services, (3) insufficient diagnosis and referral, and (4) patients' reluctance to accept ESRD therapy, due to cultural or personal concerns. A state-level regression of elderly rates on those aged 40 to 64 years indicates the variation in treatment incidence among the elderly may be due to factors other than variation in true incidence, which the middle-aged rates reflect more closely. Residual analysis corroborates the visual impression of the maps of low ESRD treatment incidence in several southern states, where referral to dialysis may be as much as 40% lower than the national level. Further research on factors contributing to low treatment incidence, including competing risks, regional lags relative to the national trend to dialyze more elderly patients, and lack of access to health care resources, is indicated. PMID- 1621680 TI - Patients with a low income have reduced renal allograft survival. AB - The impact of socioeconomic factors on long-term outcome after renal transplantation is unknown. We examined the effects of family income among 202 patients transplanted between 1976 and 1982 who had an allograft that functioned for at least 1 year. Compared with patients with an adequate income, recipients of medical assistance at the time of transplantation were more likely to return to dialysis after 1 year (16/45 [36%] v 26/157 [17%], P less than 0.01), or after 5 years of graft function (10/38 [26%] v 12/116 [10%], P less than 0.01). Patients who complied with fewer than 85% of visits during the first 2 years were also more likely to return to dialysis after 1 year (17/49 [35%] v 25/153 [16%], P less than 0.01), or after 5 years (8/31 [26%] v 14/123 [11%], P less than 0.05) than were more compliant patients. However, noncompliance was not different in patients with and without a low income (37/157 [24%] v 12/45 [27%], P greater than 0.05). The relative risk for returning to dialysis after 5 years was 2.4 (P less than 0.05) for low income and 3.0 (P less than 0.05) for less than 85% compliance using a Cox proportional hazards model. These effects were independent of prior transplantation, mismatches, pre-formed antibodies, delayed graft function, age, sex, diabetes, alcohol or drug abuse, education, race, distance from the transplant center, and living in an urban environment (relative risk = 2.5, P less than 0.05). Neither income nor compliance could be linked to death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621681 TI - The effect of aging on glomerular hemodynamics in the rat. AB - Glomerular hemodynamics were measured in male Sprague-Dawley rats, aged 4 to 5 months (young) or 20 to 22 months (old). Body weight (BW) and left kidney weights (KW) were higher in old rats than young (BW: 507 +/- 12 g v 342 +/- 11 g, P less than 0.001; KW: 2.0 +/- 0.1 g v 1.3 +/- 0.1 g, P less than 0.001). Arterial blood pressure (AP) was slightly higher in old rats, but within the normotensive range (106 +/- 4 mm Hg v 94 +/- 4 mm Hg, P less than 0.05). Glomerular filtration rate (GFR; factored for KW) was lower in old versus young rats (0.67 +/- 0.05 mL/min/gKW v 1.00 +/- 0.08 mL/min/gKW, P less than 0.02). The cortical surface of the kidney in old (but not young) rats showed marked heterogeneity and single nephron (SN)GFR was measured only in filtering nephrons and was higher and more variable in old versus young rats. Glomerular blood pressure (PGC) was unchanged in old compared with young rats (53 +/- 4 mm Hg v 55 +/- 2 mm Hg). There was a significantly greater level of glomerular sclerosis (in outer cortical glomeruli) in old versus young rats, and glomerular volume was substantially greater in old rats. This study suggests that age-related glomerulopathy is not primarily mediated by glomerular capillary hypertension. PMID- 1621682 TI - The albumin dilemma. PMID- 1621683 TI - Looking upon the water. It's our Gummit and we're stuck with it! PMID- 1621684 TI - Diabetic glomerulosclerosis and chronic renal failure with absent-to-minimal microalbuminuria. AB - We report the case of an elderly black woman with a 20-year history of insulin independent diabetes mellitus (IDDM), chronic renal failure, hypertension, proliferative retinopathy, and classical histologic features of diabetic glomerulosclerosis on renal biopsy. Repeat determinations of urinary albumin excretion rates failed to disclose significant microalbuminuria. This presentation should remind the clinician that a small minority of patients with IDDM of long duration may have severe diabetic glomerulosclerosis and renal insufficiency without detectable microalbuminuria. PMID- 1621685 TI - Glomerulonephritis and non-Hodgkin's lymphoma: a report of two cases and review of the literature. AB - Two cases of glomerulonephritis associated with non-Hodgkin's lymphoma (NHL) are described. The first patient presented with the nephrotic syndrome and normal renal function, whereas the second suffered from recurrent acute renal failure together with a unique pattern of IgM deposition within glomerular capillaries. Our review of the literature suggests that this association, although rare, has been documented in a sufficient number of cases to show that it is more than coincidental. Whereas the most common renal lesion associated with Hodgkin's disease is minimal change disease, more advanced glomerular changes are found in the patients with NHL. This is reflected in the higher incidence of renal failure in the latter patients. Treatment of the lymphomas has been shown to result in improvement or even cure of the renal disease, although long-term follow-up is rarely available in the reported cases. PMID- 1621686 TI - Erosive spondyloarthropathy in primary hyperparathyroidism without renal failure. AB - A patient with erosive spondyloarthropathy (ESA) and primary hyperparathyroidism is described. In the past, ESA has been described exclusively in patients with chronic renal failure (CRF) and has been attributed to crystal deposition, amyloidosis, severe secondary hyperparathyroidism, or other abnormalities of chronic renal failure. This patient with normal renal function suggests that secondary hyperparathyroidism plays the major pathogenetic role in ESA in patients with renal failure. PMID- 1621687 TI - Acute glomerulonephritis following infection with Chlamydia psittaci. PMID- 1621688 TI - A strategy for delineating risks due to exposure to neurotoxic chemicals. AB - A method for delineating the risks due to exposure to neurotoxic chemicals based upon the linkage of four national computer-based registers is described. The four registers are: the Danish Product Register database, PROBAS; Register of air pollution measurements in Danish workplaces, ATABAS; Register of notified occupational diseases; and Register of work force. Based on the information from the four registers, risk profiles for neurotoxic chemicals in 69 industrial groups were generated. The risk profiles describe the number of neurotoxic chemicals, their potency, the number of exposure measurements exceeding the occupational exposure limit (OEL), and the total and relative number of diseases caused by the chemicals in each group. Based on this linkage, twelve industries are noted to be potentially at high risk due to exposure to neurotoxic chemicals; therein, 18 chemicals are identified as "risk chemicals," primarily used in 8 main groups of products. The goal of the evaluation is to develop a tool for priority setting of preventive measures. The evaluation may also serve as a tool for assessing improvements and selecting areas for further epidemiological studies. PMID- 1621689 TI - Assessment of occupational exposure to cadmium in The Netherlands, 1980-1989. AB - One thousand five hundred fifty urine samples and 1,295 blood samples, collected from 919 workers, were analyzed for cadmium (Cd). The workers were employed at 16 different types of workplaces. In about 7.5% of the samples, the concentration of Cd exceeded the biological limit values proposed by the Dutch Expert Committee for Occupational Standards. Levels higher than these values were measured in both urine samples and blood samples of workers involved in electrochemical plating, in production of Cd-stabilizers and enamels, and in soldering with silver-cadmium solder. Significantly higher concentrations of beta 2-microglobulin (MG) were found in urine samples with CdU greater than 10 micrograms/g creatinine. Cd levels in urine increased with age. PMID- 1621690 TI - Lung cancer risk among workers exposed to man-made mineral fibers (MMMF) in the Swedish prefabricated house industry. AB - Mortality and cancer incidence was investigated among 2,807 workers, employed for at least one year before 1972, at 11 Swedish companies manufacturing prefabricated wooden houses. A total of 1,068 workers had been exposed to man made mineral fibers (MMMF) used for insulation. Mortality was followed from 1969 to 1988 and cancer incidence from 1969 to 1985. Exposure conditions were investigated at all plants. There were 14 deaths from lung cancer in the total cohort, whereas 20.7 would be expected (SMR = 68; 95% CI:37-113), based on regional mortality. After a latency of 20 years of more, two lung cancer cases had occurred among all workers exposed to MMMF, whereas 4.3 would be expected (SMR = 46; 95% CI: 5-168). The exposure levels that have prevailed do not seem to be associated with an increased lung cancer rate, but extended follow-up is necessary for a definitive evaluation. PMID- 1621691 TI - Accelerated loss of lung function and alveolitis in a longitudinal study of non smoking individuals with occupational exposure to asbestos. AB - Long-term asbestos workers who insulate pipes and boilers may develop interstitial lung disease associated with loss of lung function. To quantitate annual loss of lung function, 77 individuals with chest X-rays greater than or equal to 1/0 ILO category who were life-long non-smokers or ex-smokers for greater than 5 years were evaluated. Study parameters included pulmonary function tests and bronchoalveolar lavage for a mean of 3 visits over 30 +/- 2 months. The study participants were 56 +/- 1 years old and had 31 +/- 1 years' occupational exposure to asbestos. At the first visit, multiple regression analysis revealed significant associations between rales or radiographic opacities and VC, FEV1, and total lung capacity; significant associations were also found between neutrophils/ml lavage fluid with FEV1 and diffusing capacity (all p less than 0.05). Annual declines for the asbestos-exposed were VC -92 +/- 28 ml/yr and FEV1 -66 +/- 21 ml/yr. Declines in VC and FEV1 were less in those with reduced lung function at the initial visit. There were no significant associations between any of the annual declines and cells recovered by bronchoalveolar lavage. Compared to other asbestos-exposed cohorts followed longitudinally, asbestos insulators with radiographs greater than or equal to 1/0 and exposure greater than or equal to 20 years have larger rates of FVC and FEV1 decline for both non-smokers and ex smokers. PMID- 1621692 TI - Irregular opacities in the lung, occupational asthma, and airways dysfunction in aluminum workers. AB - We examined chest X-rays, measured expiratory flows and FVC by spirometry and TLC by projected lung area, ascertained respiratory data by questionnaires, and performed chest examinations in 670 Southeastern aluminum workers and 659 unexposed regional controls. Both groups were asbestos exposed. More aluminum workers had irregular opacities and fewer had pleural abnormalities than did regional pipefitter referents. The pulmonary function tests were expressed as percentage of predicted to adjust for height, age and duration of smoking based on a randomly selected U.S. reference population. Data from aluminum workers were compared to regional controls with students "t" tests run for unequal size groups. Aluminum workers had significant reductions in FEV1 of 3.2% predicted (p less than .003), FEF25-75 of 11.3% predicted (p less than .0001), FEF75-85 of 22.5% predicted (p less than .0001), and an increased TLC of 2.0% predicted (p less than .005). The 145 who had never smoked (NS) were compared with 124 NS controls and showed this same pattern of differences; but in smokers, the differences were significant for mid and terminal flows, but not for FEV1. In aluminum workers who never smoked, asthma prevalence by history was 7.6% vs. 4.0% in controls, and wheezes were heard in 21.4% vs. 2.4% in controls. In aluminum workers who were current smokers, asthma prevalence was 16.4% vs. 9.4% in controls, and wheezes were heard in 43.7% vs. 21.1% in controls. Aluminum workers had significantly more asthma, wheezing, airways obstruction, and pulmonary parenchymal abnormalities similar to asbestosis than did regional blue collar controls not melting and casting aluminum. PMID- 1621693 TI - Chest radiographs in subjects with asbestos-related abnormalities: comparison between ILO categorizations and clinical reading. AB - The findings of a previous chest X-ray screening, determined without using standardized criteria, were reassessed by means of the ILO classification. Of 470 radiographs that had been determined as showing asbestos-related changes, 430 were categorized according to the ILO Classification. Small opacities with profusion greater than or equal to 1/0 were described in 39 (52%) of 75 participants who, on the original clinical reading, had been determined as having lung fibrosis, and in 45 (12.7%) of 355 who were determined as having pleural changes only. When considering circumscribed pleural thickening at the chest wall or diaphragm, as categorized by the ILO Classification, such changes were present in 401 (93.7%) of 428 subjects with pleural changes as determined on the clinical reading. In addition to the improved sensitivity and specificity achieved, the ILO Classification also allows comparison with other studies. The most apparent disadvantage of the ILO system is that it cannot firmly separate the various types of asbestos-related pleural changes. The study revealed that the previous asbestos exposure of the case subjects had occurred in many different workplaces and occupations. PMID- 1621695 TI - Renal cell cancer among architects and allied professionals in Sweden. AB - The Swedish Cancer-Environment Registry was used to evaluate a recent report of a large excess risk of renal cell cancer among architects in Los Angeles. We identified 131 renal cell cancers among male Swedish architects and allied professionals during a 19-year follow-up period (1961-1979). Compared with the Swedish population, there was no significant excess of renal cell cancer among architects and allied professionals (standardized incidence ratio (SIR) = 1.15; 131 cases). Although it was not possible to estimate the risk for architects alone, the SIR was only 1.06 (16 cases) in a subset of professionals employed in architectural and engineering firms. However, a significant increase in risk (SIR = 1.38) was observed in a related group of workers employed as engineers and construction supervisors in the home construction industry. PMID- 1621694 TI - A mortality cohort study of seamen in Italy. AB - A total of 2,208 male subjects, enrolled as merchant marine seamen at the Civitavecchia (Italy) harbor from 1936 to 1975 were followed up through 1989 in order to evaluate their mortality experience. Available information about the number of sailings made it possible to divide subjects into two subgroups: 948 workers with at least one sailing (cohort A) and 1,260 with no reported sailing (cohort B). Fewer than expected overall deaths were observed in both cohorts (cohort A: SMR = 0.83; cohort B: SMR = 0.81), mainly due to a lower mortality from circulatory, respiratory, and digestive diseases. Lung cancer deaths were significantly increased in cohort A (O = 30, SMR = 1.71, 95% CI = 1.15-2.44), whereas no excess was observed in cohort B (O = 6, SMR = 0.57, 95% CI = 0.21 1.26). Among subjects employed aboard ship, a trend in SMRs for lung cancer increasing with duration of employment was observed. Furthermore, three neoplasms of other parts of the respiratory system (including one mesothelioma) were detected in cohort A (SMR = 5.87), and one in cohort B. The study substantiates an increased risk of respiratory cancer among subjects with an occupational history of sailing; past exposure to asbestos and to other environmental carcinogens aboard could be implicated. PMID- 1621696 TI - Bladder cancer and occupation in Shanghai, 1980-1984. AB - To investigate occupational determinants of bladder cancer in the urban area of Shanghai, occupation and industry information for 1,219 incident bladder cancer cases diagnosed during the period 1980 to 1984 were compared with 1982 census data on employment. Standardized incidence ratios (SIR) for bladder cancer were estimated for occupation and industry classifications. Significant excess risks were observed for plastic products workers (male: SIR = 432; female: SIR = 368); textile bleachers, dyers, and finishers (male: SIR = 169); metal refining and processing workers (male: SIR = 139; female: SIR = 197); petroleum refining workers (male: SIR = 2152); railway engine drivers and firemen (male: SIR = 683); and workers employed in industries of apparel and other textile products manufacturing (female: SIR = 204); paper processing (male: SIR = 146; female: SIR = 226); organic chemical manufacturing (male: SIR = 186); plastic product manufacturing (male: SIR = 218; female: SIR = 272); and metallurgy (male: SIR = 107; female: SIR = 561). This study indicates that many of the industries and occupations that are responsible for increased risk throughout the world are also associated with occupational bladder cancer in Shanghai. PMID- 1621697 TI - Exposure to diesel exhaust in the trucking industry and possible relationships with lung cancer. AB - We previously reported that long-term truck drivers and mechanics in the Teamsters Union had higher lung cancer risks than Teamsters outside the trucking industry. We now summarize results from an industrial hygiene survey of current exposures to diesel exhaust in the trucking industry, and relate these to our prior results pertaining to lung cancer risk. PMID- 1621698 TI - On the need for reform of the OSHAct. PMID- 1621699 TI - Epidemiology of work-related musculoskeletal disorders of the neck and upper limbs: a response. PMID- 1621700 TI - Non-back occupational injuries. PMID- 1621701 TI - Case comment: Moore v. Regents of the University of California. AB - The increasing use of human tissues in medical research has spawned a host of ethical and legal debates. Legal analysis in this area has almost exclusively focused on the question of property rights in both the tissues used in research and in the resulting products. One illustrative case is Moore v. Regents of the University of California, in which a patient sued his doctor for conversion of his spleen which had been removed for therapeutic purposes. The doctor later used the spleen to develop a patented and profitable cell-line. This Comment examines and rejects the property law approach to this issue. Instead, this Comment proposes two legislative changes which would 1) eliminate any trade in human tissues and 2) require doctors to inform their patients of any research interest in proposed medical procedures. These proposals resolve the problem presented in Moore, and avoid the misleading, and inevitably unanswerable, question of property rights. PMID- 1621702 TI - Medically futile care: the role of the physician in setting limits. AB - In an effort to clarify the concept of "medically futile care," two types of futile care are identified: 1) care that produces no demonstrable effect; and 2) care that produces an effect that is believed by the speaker to be of no net benefit. It is the second type of futile care, when a patient or surrogate and the clinician disagree over the benefit that the patient will receive from an intervention, that is most interesting morally and that cannot properly be labelled medically futile. As such, decisions to limit access to care deemed futile should not rest with medical professionals. This Article argues for a limited duty of clinicians to provide life-prolonging and some other fundamental care that is equitably funded and desired by the patient while competent, even if the clinician believes that such interventions will produce no net benefit. PMID- 1621703 TI - Denial of health care and informed consent in English and American law. AB - Health care rationing has gained greater visibility in the United States and the United Kingdom, for quite different reasons. As patients in both countries become more aware that potentially beneficial medical services can be denied them on economic--as opposed to purely medical--grounds, they are beginning to seek help from the judiciary. This Article contends that as rationing becomes more explicit, the doctrine of informed consent will come under increased pressure. The Article suggests that courts and legislatures consider imposing a legal obligation on physicians to inform their patients when potentially effective treatment is to be withheld for economic or other non-clinical reasons. PMID- 1621704 TI - Emerging parallels in the American health care and legal-judicial systems. AB - The structure and principal decision-making processes of the American health care system have, in recent years, evolved to closely resemble those of the legal judicial system. This transformation reflects important common values that underlie both systems, including the values of life and liberty. This Article analyzes quasi-legal features of the health care system and draws conclusions about how those features might be used to address the problem of health care rationing. It concludes that coverage rules, if properly developed, can provide the sort of objective framework necessary to evaluate claims of health care needs. This Article also demonstrates that by defining legitimate health care needs, society can thereby potentially eliminate or forestall the need to ration necessary care. This can be achieved by using carefully developed coverage rules, rather than the informal rules currently in place, in conjunction with already existing due process methods for interpreting and implementing those rules. PMID- 1621706 TI - Patient care compromised in college athletics programs. PMID- 1621707 TI - Hospital told to hire HIV+ pharmacist. PMID- 1621708 TI - Electronic cap device helps medication compliance in hypertensive patients. PMID- 1621705 TI - Mothers and children last: the Oregon Medicaid experiment. AB - In 1989 and 1991, the Oregon legislature enacted a series of initiatives to extend health coverage to uninsured state residents. Among these initiatives is an act that seeks to extend a modified set of Medicaid benefits to state residents with family incomes below the federal poverty level. This act also reduces benefits the state is now required to provide to Medicaid-enrolled women of childbearing age and children. This Article explores the legal context in which the Oregon Medicaid experiment must be evaluated. It argues that by reducing the level of coverage to which tens of thousands of exceedingly poor, Medicaid-eligible women and children are entitled, the experiment falls outside the scope of valid research that the United States Department of Health and Human Services may either sanction or fund. The Article also discusses the implications of the Oregon experiment, if approved, for the future direction of the Medicaid program in particular, and for health care reform for the poor, generally. PMID- 1621709 TI - Searle starts telephone reminder program for patients taking verapamil product. PMID- 1621710 TI - Lederle program promotes pharmacist's role in helping smokers quit. PMID- 1621712 TI - Schering report looks at pharmacist's role in improving patient compliance. PMID- 1621711 TI - To help curb TB, New York workers will watch patients take their medicine. PMID- 1621713 TI - Acceptability of a deemed-signed policy for oral orders. PMID- 1621714 TI - Making the transition from intern to pharmacist. PMID- 1621715 TI - Overcoming resistance to change. PMID- 1621716 TI - How to achieve teamwork between pharmacists and technicians: a pharmacist's perspective. PMID- 1621717 TI - Cisplatin overdosage. PMID- 1621718 TI - Pharmacists as managers of risk, quality, and cost. PMID- 1621719 TI - Planning for financial impact of antiendotoxin monoclonal antibodies. PMID- 1621720 TI - Department of pharmacy practice chairpersons' opinions of the joint statement. PMID- 1621721 TI - Pharmacists and postmarketing restriction of drug products. PMID- 1621722 TI - AJHP's mission as a membership journal. PMID- 1621723 TI - Effects of pharmaceutical care on medication cost and quality of patient care in an ambulatory-care clinic. AB - The effects of pharmaceutical care on medication cost and quality of care in a university-based family-practice clinic were studied. Prognostic indicators were used to target patients who should receive pharmaceutical care. Those patients who received care. Those patients who received pharmaceutical care over a 14 month period during 1988-89 were included in the study. A pharmacist interviewed each targeted patient, obtained the patient's medication history, made therapeutic recommendations to the patient's physician, and counseled the patient on his or her therapy. The pharmacist's recommendations were noted, and the outcome of each recommendation was documented on subsequent patient visits. For each recommendation, drug cost avoidance was calculated and patient outcome was analyzed. For quality assessment, a panel of three health-care professionals reviewed the pharmacist's recommendations for 25% of the study patients (randomly selected) and noted their agreement or disagreement with the pharmacist's actions. Over the study period, 184 targeted patients received pharmaceutical care. Clinic physicians accepted 297 (82.5%) of 360 pharmacist recommendations. Annual extrapolated cost avoidance associated with the pharmacist's recommendations was $19,076. For 213 (80.4%) of the 265 accepted recommendations for which outcome data were available, improvement or resolution of the patient's disease state occurred. For 8 (16%) of 50 unaccepted recommendations, the patient's status declined. The peer review panel agreed with 86% of the pharmacist's recommendations. The provision of comprehensive pharmaceutical care in an ambulatory-care clinic can both reduce medication costs and improve quality of care. PMID- 1621724 TI - Drive-up prescription refill service at a large Navy medical facility. AB - A drive-up prescription refill service at a large naval medical facility is described. A pharmacy drive-up refill service was created to reduce customer congestion, to reduce demand for parking, and to improve customer service. The drive-up program is staffed by a full-time pharmacy technician, a full-time volunteer, and a part-time pharmacy technician who assists during lunches, breaks, and peak hours. Customers must request refills by telephone, and requests are recorded by a pharmacy answering machine. Recorded requests are transcribed, processed, and checked by a pharmacist in the main pharmacy. Refills ready for pickup are transported to the drive-up site twice daily. If a refill is missing, the customer is asked to park, fill out a missing refill form, and pick up the refill at the main pharmacy. Approximately 700 prescription refills are processed and filled daily at the drive-up service. The addition of a drive-up refill service reduced customer visits to the outpatient pharmacy department by about one third and reduced demand for parking by a projected 360-400 parking spaces per day. The error rate for missing refills is less than 0.5%. The only negative consequence of the drive-up service is less interaction between the customer and the pharmacy staff for counseling. A drive-up refill service at a large naval medical facility reduced customer congestion, reduced parking demand, and improved customer service at the outpatient pharmacy department. PMID- 1621725 TI - Use of prescription-refill records to assess patient compliance. AB - Prescription-refill records were used to assess patient compliance, to evaluate factors previously associated with compliance, and to determine the association between selected drugs and compliance. Records were selected from a computerized database containing prescription-coverage claims, based on the following criteria: (1) the prescriptions were refilled during 1987-1989 and within two times the days' supply after the dispensing date, (2) they involved any of 12 drugs selected for study, (3) they required one to four doses per day, and (4) at least 20 records with the same regimen were available. Compliance was defined as refill within 0.2 times the days' supply after the refill-due date, and it was assessed by calculating the compliance rate and the compliance index (which describes the relationship between the refill-due date and the actual refill date). Data from 19,118 prescription-refill records were analyzed. The compliance index improved slightly as the number of concurrent medications increased, worsened as the number of doses per day increased, and improved as the immediacy of the risk of noncompliance increased. Different medications and indications were associated with different degrees of compliance. Medication compliance generally improves as the number of daily doses decreases, may improve slightly as the number of concurrent medications increases, and varies with the particular drug and indication. PMID- 1621726 TI - Drug-related emergency department visits and hospital admissions. AB - The incidence and causes of drug-related hospital admissions and visits to an emergency department were evaluated. A retrospective chart review was conducted to identify drug-related visits and admissions for all patients who visited the emergency department of a 517-bed tertiary-care institution during a four-month period. Drug-related illnesses were classified as adverse drug reaction (ADR), overdose or abuse, noncompliance, drug interaction, or toxicity. Patient data included demographic characteristics, medication history, serum drug concentrations, length of hospital stay, and hospital admission charges. Of 10,184 patients who visited the emergency department, 293 (2.9%) had drug-related illnesses; 71 (24%) of these patients were admitted. The drug classes most commonly involved were drugs of abuse (23.2%), anticonvulsants (17.1%), antibiotics (12.6%), respiratory drugs (8.9%), and pain medications (8.9%). The most common category of drug-related illness was overdose or abuse (35%) followed by noncompliance (28%), ADR (28%), toxicity (8%), and drug interaction (1%). The average length of stay for patients who were admitted was 5.8 days, and the average cost of admission was $8888. Drug-related illnesses accounted for 2.9% of hospital admissions and visits for patients in the emergency department. The most commonly identified drug-related illnesses were overdose or abuse, noncompliance, and ADRs; the drug classes most commonly implicated were drugs of abuse, anticonvulsants, and antibiotics. PMID- 1621727 TI - Pharmacy-based antimicrobial-monitoring service. AB - A pharmacy-based antimicrobial-monitoring service at a university teaching hospital is described. The service was developed and implemented by the pharmacy department in 1987. Antimicrobial drugs that can be misused, that are expensive, or for which bacterial resistance is a concern were targeted. When a pharmacist receives an order for a targeted antimicrobial, an antimicrobial-monitoring card is completed. Monitored drugs meeting approved criteria are dispensed as ordered. When the antimicrobial does not meet the criteria, the pharmacist contacts the physician and suggests an alternative. If the alternative is not accepted, the infectious diseases service is contacted and then informs the pharmacy department about the status of the drug. The agent is dispensed if no response is received within two hours. Qualified staff pharmacists rotate through the position of antimicrobial pharmacist, whose responsibilities include reviewing antimicrobial use throughout the hospital, checking relevant laboratory test results, and recommending adjustments to regimens. From July 1989 to June 1990, 3546 orders for monitored antimicrobials were reviewed; of these, 86% met the criteria, 9% did not meet the criteria but were approved, 2% were for drugs that were replaced by alternative therapies, 1% were for agents that were dispensed because the pharmacist was not contacted, and 2% represented medical staff overrides or drugs dispensed inappropriately. Pharmacist and physician compliance with the monitoring policy has been high. A positive, constructive, and educational relationship exists between pharmacists and physicians vis-a-vis the service. A pharmacy-based antimicrobial-monitoring service has been accepted by pharmacists and physicians and appears to be having a positive impact on prescribing habits. PMID- 1621728 TI - Hospital selection of home infusion therapy companies as preferred providers. AB - The process by which a hospital selected home infusion therapy providers is described. Administrators at a 379-bed teaching hospital decided to attempt to reduce the high mean length of stay by expanding the use of home infusion therapy. Direct diversification into this field by the hospital was not feasible, so it was decided to establish contractual agreements with providers. A task force was appointed to evaluate and choose vendors in the area and to increase the number of patient referrals. The task force examined reports on past experience with providers, price lists, the range and level of services offered, and the amount of free care given and visited the companies' facilities. The group designated three providers as preferred and two as unacceptable. The number of patients referred increased from 21 during the 12 months before the task force was convened to 46 in the first 9 months afterward, for a saving of 2198 patients days. After one year the task force met again to consider company requests for evaluation or reevaluation, establish a plan for publicizing the benefits of home infusion therapy, and replace the site visits with a requirement for accreditation by the Joint Commission. After two years, the task force developed provider-evaluation criteria to streamline the process and reflect the experience gained. The responsibility for reviewing providers was transferred to the P&T committee. When a direct venture into home infusion therapy is not fiscally desirable, contracting for services can still offer the advantages of reduced length of stay and decreased drug expenses. PMID- 1621729 TI - Evaluation of a disposable, elastomeric infusion device in the home environment. AB - The use of a disposable, elastomeric infusion device was evaluated in 55 patients receiving home antimicrobial therapy. During a 30-day period, all patients referred to five service centers to receive home antimicrobial therapy for at least one week were enrolled in the study. Pharmacists used an automated pump to fill 110-mL, 100-mL/hr elastomeric devices (Homepump; Block Medical, Carlsbad, CA). Nurses trained patients to use the device. Nurses and pharmacists completed an evaluation form for each patient. Fifty-five patients received a total of 1938 doses; a fresh device was used to administer each dose. Nurses described patient teaching for the device as easy (51) or no different from that for other devices (4). Patient acceptance was reported to be good in 54 patients and poor in 1 patient. A total of 91 restarts were required; 36 patients needed more than one restart. The failure rate of the device was 1.6%; 25 of 44 reported problems occurred in devices that were frozen and thawed before use. The Homepump was determined to be an acceptable device for the intermittent infusion of small volume antimicrobial solutions in the home environment because of its low failure rate and high degree of patient and nursing preference; its drawbacks include high cost and slowed infusion rates for units that are not thawed properly after freezing. PMID- 1621730 TI - Stability of procainamide hydrochloride in an extemporaneously compounded oral liquid. AB - The stability of procainamide hydrochloride 5, 50, and 100 mg/mL in an extemporaneous oral liquid formulation was studied. Oral liquids containing procainamide hydrochloride 5, 50, or 100 mg/mL were compounded from procainamide hydrochloride capsules, sterile water for irrigation, and cherry syrup or a 70:30 mixture of 1% methylcellulose and cherry syrup. The pH values of the liquids were 6 (unadjusted) and 5 (adjusted). The liquids were stored at 4-6 degrees C or 24 25 degrees C and tested for drug concentration by stability-indicating high performance liquid chromatography at 0, 7, 14, 21, 28, 34, 147, and 180 days. The relationships among the variables drug concentration, type of vehicle, pH, and temperature and their effects on drug stability were analyzed by using repeated measures analysis of variance. With respect to effects on stability across time, there was a significant three-way interaction among drug concentration, type of vehicle, and temperature. The effect of concentration on stability seemed to depend on the vehicle used, but this dependence was different for different temperatures and different pH values. When trends over time were considered, a significant interaction among time, vehicle type, and temperature was found. This reflected the stability of the concentration of procainamide hydrochloride over time under refrigeration for both vehicles, compared with the steady decline in drug concentration at room temperature. Overall, drug concentration was fairly stable over time in the 5- and 50-mg/mL oral liquids but declined steadily in the 100-mg/mL liquid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621731 TI - Pharmacist's responsibility for providing drug information to be used for questionable purposes. PMID- 1621732 TI - Pharmacy-based medication administration program. PMID- 1621733 TI - U.S. system for organ procurement and transplantation. AB - The establishment and responsibilities of the organ procurement and transplantation network in the United States are discussed, and the process of receiving an organ transplant through the system is described. The National Organ Transplant Act of 1984 provided for a federally funded network for organ procurement and transplantation, which would function as a private, non-profit organization. This organization is the United Network for Organ Sharing (UNOS). UNOS monitors the activities of and provides service to transplant centers and organ procurement organizations (OPOs). The names of all candidates awaiting cadaveric organ transplants are placed on a central waiting list maintained by UNOS; UNOS also is responsible for maintaining a scientific registry to collect relevant data from transplant centers on the recipients of organ transplants. Although there is a national list of more than 25,000 persons waiting at any given time for a cadaveric organ, there are far fewer actual organ donors (less than 5000 in 1991). The hospital's best resource with respect to the donation process is the local OPO, which provides services related to organ donor referral, evaluation, and surgical recovery. The organ donation process consists of eight components: donor identification, referral, evaluation, consent, management, recovery of organs, allocation, and follow-up. An organ recovery coordinator from the local OPO helps the hospital staff in determining donation potential, seeking consent from the next of kin, and managing the donor after consent has been obtained. The OPO--never the donor's family or their insurer--is billed for charges relating to the donation. The OPO then bills the costs associated with the donation to the transplant centers receiving each organ for implantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621734 TI - Guidelines for performing a pharmacoeconomic analysis. AB - The fundamentals of pharmacoeconomics are presented. Pharmacoeconomic research is used to identify, measure, and compare the costs, risks, and benefits of programs, services, or therapies and determine which alternative produces the best health outcome for the resources invested. Each pharmacoeconomic method measures costs in monetary terms; the differences lie in the valuation of outcomes. In cost-minimization analysis, the outcomes are considered to be equal and therefore are not measured. Cost-benefit analysis measures outcomes in dollars, whereas cost-effectiveness analysis measures outcomes in nonmonetary units. In cost-utility analysis, outcomes expressed in nonmonetary units are adjusted for health-related quality of life. A well-designed pharmacoeconomic analysis involves 10 steps: (1) defining the problem, (2) determining the study's perspective, (3) determining the alternatives and outcomes, (4) selecting the appropriate pharmacoeconomic method, (5) placing monetary values on the outcomes, (6) identifying study resources, (7) establishing the probabilities of the outcomes, (8) applying decision analysis, (9) discounting costs or performing a sensitivity or incremental cost analysis, and (10) presenting the results, along with any limitations of the study. By adhering to the analytic steps described, the pharmacist undertaking a pharmacoeconomic evaluation has the greatest likelihood of obtaining valid and useful results. PMID- 1621735 TI - Government liable for failure to monitor a patient's serum gentamicin concentration in an Army hospital. PMID- 1621736 TI - Pharmacy, politics, and public policy. PMID- 1621737 TI - Pharmacy implications of clinical guideline development. PMID- 1621739 TI - Advances in outpatient antimicrobial therapy: loracarbef. June 12-15, 1991, San Francisco, California. Proceedings. PMID- 1621738 TI - Programs for monitoring inappropriate prescribing of controlled drugs: evaluation and recommendations. PMID- 1621740 TI - Pharmacokinetic profile of loracarbef. AB - Loracarbef, the first beta-lactam antibiotic of the carbacephem class to undergo clinical evaluation, has been the subject of extensive clinical pharmacology studies. Loracarbef is well absorbed: virtually all of an orally administered dose is excreted in the urine unchanged. Following administration of a 400 mg capsule to adults twice a day for 10 days, no accumulation of drug is noted. In one study in children, following the administration of 15 mg/kg of loracarbef suspension, the mean maximum plasma concentration (Cmax) was 20.3 micrograms/mL. In adults, the Cmax following administration of the suspension or solution formulations is higher than that achieved following administration of the capsule formulation, and the time to reach peak concentration (Tmax) is increased when loracarbef is administered as a capsule; however, the area under the curve, plasma half-life, and percentage of oral dose excreted in the urine are comparable among all formulations. The ingestion of food decreases the Cmax and delays the Tmax compared with the fasting state. The pharmacokinetic profile of loracarbef in adults is comparable with that in children or the elderly. Because loracarbef is eliminated primarily by the kidney, dosage must be reduced in patients with moderate-to-severe renal insufficiency. Loracarbef achieves middle ear and interstitial-fluid levels that generally exceed the minimum inhibitory concentrations for common bacterial pathogens. Loracarbef possesses a pharmacokinetic profile consistent with the efficacy and safety profile documented in controlled clinical trials. PMID- 1621741 TI - The carbacephems: a new beta-lactam antibiotic class. AB - The carbacephems are a new class of beta-lactam antibiotics that are similar in structure to the cephalosporins. Carbacephems differ from cephalosporins, however, in the substitution of a sulfur atom in the dihydrothiazine ring with a methylene group to form a tetrahydropyridine ring. The result of this structural difference is the carbacephem class. Carbacephems have remarkable chemical stability that allows for structural manipulation in a manner that could not be done previously with the cephalosporin ring system. Potent broad-spectrum antibiotics result from the incorporation at the 3 position of substituents that include quaternary pyridinium or imidazole, sulfones, and heterocyclic thiazole structures. Because of the chemical stability of the carbacephems, these highly electronegative side chains can be added to the 3 or 3' position of the tetrahydropyridine ring system. Increasing the electronegativity of these side chains can increase the microbiologic activity of the compounds. In addition, utilizing the side chains that have traditionally conferred good oral absorption on the cephalosporins offers the possibility of a new series of broad-spectrum oral antibiotics. Loracarbef is the first carbacephem to undergo clinical development, and other experimental carbacephems are being produced with the aim of developing potent oral antibiotics that can be used against pathogens that cause infections commonly found in the outpatient setting. PMID- 1621742 TI - The safety profile of loracarbef: clinical trials in respiratory, skin, and urinary tract infections. AB - The efficacy and safety of the antibiotic loracarbef have been demonstrated in a series of 22 clinical trials involving over 9,000 patients. The data compiled from these trials indicate that loracarbef is well tolerated by the majority of patients, including children and elderly patients. Most adverse events in patients receiving loracarbef were mild and transient in nature; only 1.5% of patients discontinued therapy because of drug-related adverse events. The frequency of adverse events associated with this agent compares favorably with that reported for the other antibiotics in these trials. The most commonly reported adverse reaction in the loracarbef study group was diarrhea, but this condition occurred less frequently in patients who received loracarbef than in those treated with the comparative agents. Other gastrointestinal events, such as nausea and vomiting, were reported infrequently. Headache was the second most common adverse event reported and occurred at a slightly higher frequency in the loracarbef-treated group than in patients receiving comparative antibiotics. No clinically significant alterations in laboratory parameters or gastrointestinal flora were observed following loracarbef administration. The compiled data indicate that loracarbef is a safe therapeutic option for the treatment of a wide spectrum of bacterial infections. PMID- 1621743 TI - Pathogenesis of fibrosis in acute lung injury. AB - The anatomic changes that occur in response to acute lung injury significantly impair gas exchange. As is the case with skin wounds, a fibroproliferative response follows lung injury. In the lungs, however, this can result in life threatening obliteration of alveolar air spaces. A better understanding of the mechanisms involved in lung repair may allow the development of therapies that regulate the fibroproliferative response. Studies from our laboratory have identified a peptide in bronchoalveolar lavage fluid from patients with acute lung injury that promotes the migration and replication of lung fibroblasts. This peptide is related to platelet-derived growth factor (PDGF) antigenically as well as by receptor-binding criteria; its molecular weight is 14 kilodaltons (kDa) as compared to 29 kDa for PDGF. Despite the potent activity of the 14 kDa peptide, however, such a growth signal may not be absolutely required for tissue granulation. The possibility that lung fibroblasts from patients with acute lung injury might be capable of dividing without exogenous stimulation will be examined. Another theoretical consideration is the signals that regulate termination of the fibroproliferative response. Insights into the molecular mechanisms involved in lung repair may result in therapies that modulate the sometimes maladaptive fibroproliferative response following acute lung injury. PMID- 1621744 TI - Gene therapy strategies for pulmonary disease. AB - The two most common hereditary lung disorders in Caucasians, alpha 1-antitrypsin (alpha 1-AT) deficiency and cystic fibrosis, have their major clinical manifestations in the lung. Rapid advances in biotechnology have resulted in a variety of gene therapy strategies for the potential treatment of these disorders. Three vector systems--plasmid, retrovirus, and adenovirus--have been evaluated for their possible utility in transferring genes in a fashion that would either alter the milieu of the lung or directly alter the genetic program of lung parenchymal cells. Two general strategies can be used: ex vivo modification of autologous cells with subsequent transplantation to the patient and in vivo modification with an appropriate vector containing the exogenous gene. Studies carried out in experimental animals show that it is theoretically possible to treat both alpha 1-AT deficiency and cystic fibrosis with gene therapy if the safety hurdles can be overcome to minimize the risks involved. PMID- 1621745 TI - Acute bronchitis: results of U.S. and European trials of antibiotic therapy. AB - Acute bronchitis, an illness frequently encountered by primary-care physicians, is an inflammation of the tracheobronchial tree that results from a respiratory tract infection. It is characterized by persistent cough and sputum production and is occasionally accompanied by fever and/or chest pain. Acute bronchitis may have a viral or bacterial origin and is often treated with antibiotics. Four clinical trials were conducted to compare high and low doses of loracarbef, a new oral beta-lactam antibiotic, with three agents commonly used to treat acute bronchitis: amoxicillin/clavulanate, cefaclor, and amoxicillin. Results of these studies indicated that loracarbef, 400 and 200 mg twice daily, had clinical and bacteriologic efficacy against the common respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella (Branhamella) catarrhalis that was comparable with that of the comparative agents. Loracarbef was as well tolerated as cefaclor and amoxicillin; moreover, it produced a significantly lower incidence of diarrhea than did amoxicillin/clavulanate. Loracarbef may be considered a safe and effective alternative agent for the treatment of patients with acute bronchitis. PMID- 1621746 TI - Loracarbef (LY163892) in the treatment of acute exacerbations of chronic bronchitis: results of U.S. and European comparative clinical trials. AB - Two controlled clinical trials compared loracarbef (LY163892 with amoxicillin/clavulanate or amoxicillin in the treatment of acute exacerbations of chronic bronchitis. Collectively, of 1,057 patients enrolled, 390 qualified for analysis: group 1 comprised 200 patients treated with loracarbef (400 mg twice daily); group 2, 120 patients treated with amoxicillin/clavulanate (500 mg three times daily); and group 3, 70 patients treated with amoxicillin (500 mg three times daily). Symptomatic and bacteriologic outcomes were assessed at post therapy (within 72 hours of therapy completion), and at late-posttherapy (10-14 days after therapy completion). These evaluations were combined to provide an "overall" evaluation that accounted for all unfavorable outcomes occurring at either the posttherapy or late-posttherapy visit. At the posttherapy evaluation, 93.0% of group 1 patients, 95.0% of group 2 patients, and 88.6% of group 3 patients demonstrated favorable clinical outcomes (cure or improvement). "Overall" favorable clinical outcomes were achieved in 88.0% of group 1 patients, 90.0% of group 2 patients, and 81.4% of group 3 patients. Bacteriologic results from the two studies could not be merged due to marked differences in how posttherapy bacteriologic results were assessed. The clinical significance of positive posttherapy sputum cultures was doubtful: 90% of patients with a positive sputum culture at the posttherapy visit who returned for the late posttherapy visit had successful clinical outcomes documented at the late posttherapy evaluation. Loracarbef was associated with a lower incidence of diarrhea and a higher incidence of headache as compared with amoxicillin/clavulanate. These results suggest that 400 mg loracarbef twice daily for 7 days is effective and safe in the treatment of acute exacerbations of chronic bronchitis. PMID- 1621748 TI - In vitro activity of loracarbef and effects of susceptibility test methods. AB - Loracarbef is a new oral antimicrobial of the carbacephem class with in vitro activity against the common pathogens associated with skin infections, otitis media, sinusitis, bronchopulmonary infections, and urinary tract infections. A review of the literature shows the following ranges for 90% minimum inhibitory concentration (MIC90) values (microgram/mL) against the organisms that commonly cause these illnesses: Streptococcus pneumoniae, 0.25-2.0; Moraxella (Branhamella) catarrhalis (beta-lactamase positive), 0.5-8.0; M. catarrhalis (beta-lactamase negative), 0.12-0.25; Haemophilus influenzae (beta-lactamase positive), 0.5-16.0; H. influenzae (beta-lactamase negative), 0.25-8.0; Escherichia coli, 2.0-25; Klebsiella pneumoniae, 0.25-8.0; Proteus mirabilis, 1.0 8.0; Streptococcus pyogenes, less than or equal to 0.06-1.0; Staphylococcus aureus (beta-lactamase positive), 8.0; S. aureus (beta-lactamase negative), 1.0 2.0. The in vitro activity of loracarbef against these common outpatient pathogens is similar to that of other oral antimicrobials such as cefaclor, cefuroxime axetil, cefixime, amoxicillin/clavulanate, and trimethoprim/sulfamethoxazole. The results of in vitro susceptibility tests with any antimicrobial, including loracarbef, are somewhat dependent on the specific test method that is employed in the laboratory. This is particularly true with H. influenzae. Furthermore, the results of loracarbef susceptibility tests are of uncertain value in predicting therapeutic outcome. PMID- 1621747 TI - Efficacy and safety of loracarbef in the treatment of pneumonia. AB - The treatment of bacterial pneumonia requires an agent with activity against a wide range of bacterial pathogens, including pathogens that produce beta lactamase. Loracarbef, a member of the carbacephem class of antibiotics, was tested in a series of clinical trials for its efficacy and safety in the treatment of lobar and bronchial bacterial pneumonia. Successful clinical responses were achieved in 97.6% of the evaluable patients receiving 400 mg twice daily of loracarbef. This compared favorably with the respective response rates of 92.3% for patients receiving 500 mg three times a day of amoxicillin/clavulanate and 95.0% for patients receiving 500 mg three times a day of amoxicillin for the same illnesses. Proven or presumed elimination of the pretherapy pathogen was found in 89% of the patients receiving loracarbef, 92.3% of the amoxicillin/clavulanate-treated patients, and 70.0% of those receiving amoxicillin. Loracarbef was also well tolerated, although nausea and vomiting were associated with the use of all three agents. Nevertheless, treatment with loracarbef resulted in the lowest rate of discontinuation of therapy due to drug related adverse events. Thus, these clinical trials support the conclusion that loracarbef is a safe and effective treatment for bacterial pneumonia. PMID- 1621749 TI - Acute bacterial maxillary sinusitis: results of U.S. and European comparative therapy trials. AB - Loracarbef, which is the first agent of the carbacephem class of beta-lactam antibiotics to be developed, provides good activity against a broad spectrum of bacteria. A single-blinded, randomized, parallel clinical trial in 10 centers in the United States compared the efficacy and safety of loracarbef with that of amoxicillin/clavulanate potassium in the treatment of acute bacterial maxillary sinusitis. A 7-10-day regimen of loracarbef (400 mg twice daily) was as effective as amoxicillin/clavulanate (500/125 mg three times a day) and resulted in somewhat fewer side effects. The results of a European trial in Sweden, Finland, and Iceland showed that loracarbef was clinically more effective than doxycycline in the treatment of acute bacterial maxillary sinusitis. PMID- 1621750 TI - Loracarbef versus penicillin VK in the treatment of streptococcal pharyngitis and tonsillitis in an adult population. AB - Loracarbef, a member of the carbacephem class of beta-lactam antibiotics, is a potent anti-bacterial agent. In a double-blind, randomized clinical trial to assess the efficacy and safety of loracarbef in the treatment of streptococcal pharyngitis and tonsillitis, 107 adult patients were treated with loracarbef (200 mg capsules twice a day or 15 mg/kg/day suspension) and 111 patients were treated with penicillin VK (250 mg capsules four times a day or 20 mg/kg/day suspension) for 10 days. In the loracarbef treatment group, 96.6% of the evaluable patients had a favorable clinical response 3-5 days after therapy, a result that compared favorably with the 93.9% response rate achieved in the penicillin group. The clinical failure/relapse rates were 3.4% for loracarbef-treated patients and 6.1% for patients receiving penicillin. Bacteriologic response data approximated the clinical results, with a successful response in 89.9% of the loracarbef-treated patients and 91.5% of the penicillin recipients. Two (1.9%) loracarbef-treated patients with rash and one (0.9%) penicillin-treated patient with diarrhea discontinued the study early because of these adverse events. The incidence of adverse events was comparable in the two treatment groups except for increased cough, which was reported by 3.7% of the loracarbef-treated patients and none of the penicillin recipients. These data support the conclusion that loracarbef is comparable to penicillin VK in the treatment of streptococcal pharyngitis and tonsillitis in adults. PMID- 1621751 TI - Loracarbef (LY163892) versus cefaclor in the treatment of bacterial skin and skin structure infections in an adult population. AB - Loracarbef (LY163892), a member of the class of beta-lactam antibiotics known as carbacephems, is characterized by a high level of chemical stability and a broad spectrum of antibacterial activity that persists in the presence of beta lactamase. The efficacy and safety of loracarbef, 200 mg (twice daily), and cefaclor, 250 mg (three times daily) (one patient received 178 mg of cefaclor suspension, three times daily), were compared in a randomized, double-blind, multicenter trial conducted in adults with skin and skin-structure infections due predominantly to Staphylococcus aureus. Examination within 72 hours after the completion of therapy indicated a favorable clinical response in 84 (93.3%) of the 90 loracarbef-treated patients evaluable for efficacy and in 79 (95.2%) of the 83 evaluable patients treated with cefaclor. Pathogens were eradicated in 83 (92.2%) of the patients in the loracarbef group and 74 (89.2%) of those in the cefaclor group. Only four adverse events--headache/migraine, diarrhea, abdominal pain, and nausea--occurred in greater than 2% of the total study population. The overall incidence of adverse events in the 201 loracarbef-treated and 192 cefaclor-treated patients evaluated for safety was 19.9% and 24.5%, respectively. Adverse events that required hospitalization or discontinuation of treatment occurred in four patients in the cefaclor group but in none of those treated with loracarbef. There were no statistically significant differences in the clinical or bacteriologic response or the incidence of side effects between the two treatment groups. These findings indicate that loracarbef given twice daily is comparable in safety and efficacy to cefaclor given three times daily in the treatment of adults with skin and skin-structure infections. PMID- 1621752 TI - Loracarbef (LY163892) versus cefaclor and norfloxacin in the treatment of uncomplicated pyelonephritis. AB - Optimal therapy for pyelonephritis requires the immediate administration of an effective broad-spectrum antibiotic. Because conventional oral antibiotics such as the sulfonamides and the aminopenicillins are limited by the development of resistant bacteria associated with this common disease, the therapeutic effectiveness of a new oral carbacephem antibiotic was investigated. Two double blind, randomized clinical trials of loracarbef (LY163892) were conducted. A total of 245 patients (greater than or equal to 18 years old) with uncomplicated pyelonephritis were enrolled in parallel studies. One study compared loracarbef with cefaclor; the other compared loracarbef with norfloxacin. In the combined patient population, 119 patients were treated with loracarbef (400 mg twice daily), 43 with cefaclor (500 mg three times daily), and 83 with norfloxacin (400 mg twice daily). All treatment regimens continued for greater than or equal to 14 days. A total of 68 patients in the loracarbef group, 25 in the cefaclor group, and 43 in the norfloxacin group qualified for efficacy analysis. Escherichia coli was the causative pathogen in 85.0% of these patients. Successful posttherapy clinical and bacteriologic responses were similar for all three study drugs: 94.1 and 86.8%, 96.0 and 80.0%, 97.7 and 88.4% for loracarbef, cefaclor, and norfloxacin, respectively. Late posttherapy clinical responses were 87.4, 83.3, and 91.7% for the loracarbef, cefaclor, and norfloxacin groups, respectively. Bacteriologic responses for the three groups were 79.6, 60.0, and 88.9%. The most frequent adverse effects (headache, diarrhea, and nausea) were experienced by three patients (2.5%) in the loracarbef group; headaches were noted in two (4.7%) cefaclor patients, diarrhea was noted in three (7.0%) patients in the cefaclor group, and nausea was noted in four (9.3%). Gastrointestinal events were noted in four patients (4.8%) in the norfloxacin group. The data demonstrate that loracarbef is comparable in efficacy and safety to both cefaclor and norfloxacin as oral therapy for uncomplicated pyelonephritis. PMID- 1621753 TI - Antibiotic therapy for urinary tract infections. AB - Loracarbef, a member of the carbacephem class of beta-lactam antibiotics, was tested in randomized, double-blind, parallel studies for the treatment of uncomplicated urinary tract infections (UTIs). In one study conducted in the United States, a 7-day course of once-daily doses of loracarbef (200 mg) was compared with a 7-day course of multiple daily doses of cefaclor (250 mg three times a day). Analysis of data from a small, homogeneous patient population of 108 college-aged women showed that loracarbef produced clinical and bacteriologic responses similar to those produced by cefaclor. At 5-9 days posttherapy, bacteriologic cure was observed in 96% of patients in the loracarbef group and 90% of patients in the cefaclor group (p = 0.614); at 4-6 weeks post-therapy, the same cure rate (81%) was observed in both groups. Analysis of the larger (333 patients) and more heterogeneous study population containing several male and elderly female patients showed that loracarbef again produced responses similar to those produced by cefaclor, with no statistically significant differences seen between the groups at 5-9 days or at 4-6 weeks posttherapy. The adverse events reported by the loracarbef and cefaclor groups were also comparable in both the small and large patient populations analyzed. Similarly favorable results were seen when a 7-day regimen of loracarbef (200 mg once a day) was compared with a 7 day regimen of norfloxacin (400 mg twice a day) in a large European study of approximately 300 patients with uncomplicated cystitis. These studies demonstrate that the safety and efficacy of once-daily loracarbef are comparable to the safety and efficacy of multiple-dose/day therapy with other antimicrobial agents commonly used in the treatment of uncomplicated UTIs. PMID- 1621754 TI - Hypothesis: Jadassohn nevus phakomatosis: a paracrinopathy with variable phenotype. AB - It has been postulated that the phakomatoses are paracrine growth regulation disorders (paracrinopathies). To determine how Jadassohn nevus phakomatosis (JNP) may fit such a pathogenetic model, a phenotype analysis of 13 propositi with JNP and a review of most reported JNP patients were done. The phenotypes of the propositi and the reviewed patients showed a great variability from a solitary congenital epidermal nevus to extensive cutaneous lesions with associated severe non-cutaneous anomalies. Review of long-term observations of JNP patients demonstrated considerable phenotypic changes within and beyond the boundaries of the nevi. The changes included a multitude of postnatal rare benign and/or malignant tumors and unusual manifestations: renal rickets, hepatomegaly, visceral cysts, vasculopathy, and even gangrene. Thus, a life-long predisposition to dysregulation of paracrine growth factors (GFs, regulatory peptides, peptide regulatory factors, and cytokines), foremost somatomedin-C (Sm-C, IGF-I), epidermal, fibroblast, platelet-derived GFs, and transforming GF-beta is implied. Laboratory evidence for the presumed GF dysregulation in the phakomatoses came from tissue culture study of patients with neurofibromatosis type 1 (NF-1). Compared to controls their "normal" skin showed ultrastructural changes of markedly increased number of melanin macroglobuli within the melanocytes. Paracrine GFs as relevant to hamartomatous growth were incriminated by radioimmunoassays of cutaneous neurofibromas showing two-fold or greater increase of Sm-C levels compared to the levels in the adjacent skin. Thus, NF-1 appears to be a paracrinopathy. JNP shows many more dynamic changes throughout the life span of the patients than NF-1. In the near future paracrinology may aid endocrinology and oncology in treating patients with disorders of these three growth mechanisms in man. PMID- 1621755 TI - Encephalocraniocutaneous lipomatosis and the Proteus syndrome: distinct entities with overlapping manifestations. AB - We have studied three children with cutaneous (epidermal nevi), subcutaneous (lipomas, plantar skin thickening), vascular (hemangioma, lymphangioma), skeletal (osteoma, exostosis, localized hypertrophy), and neurological (hydrocephaly, lissencephaly, partial agenesis of the corpus callosum) developmental defects associated with the Proteus syndrome and related hamartoneoplastic conditions. We compared our findings in these three patients with those of 50 others with Proteus syndrome and nine with encephalocraniocutaneous lipomatosis (ECCL) reported in the literature. We found that Proteus syndrome and ECCL have distinct identities even though some clinical manifestations are shared by both and a few patients have manifestations of both conditions. PMID- 1621756 TI - Variability versus heterogeneity in syndromal hypothalamic hamartoblastoma and related disorders: review and delineation of the cerebro-acro-visceral early lethality (CAVE) multiplex syndrome. AB - We report on a case of neonatal hypothalamic hamartoblastoma with holoprosencephaly, Hirschsprung disease, and tetramelic postaxial polydactyly. Twenty-seven previous cases of congenital hypothalamic embryonic tumours with associated congenital defects are reviewed. A classification in isolated, associated, and syndromal forms is proposed. The difficulties encountered in differential diagnosis between the syndromal form (mainly represented by the Pallister-Hall syndrome) and related diseases as Smith-Lemli-Opitz type II, holoprosencephaly-polydactyly, orofaciodigital type VI and hydrolethalus syndromes are outlined. Two pathogenic mechanisms are discussed: a classical pleiotropic model and single sequence model. The latter is sufficient to delineate syndromal hypothalamic hamartoblastoma. With the former, syndromal hypothalamic hamartoblastoma cannot be clearly recognized in the absence of a CNS tumour, a child with syndromal hypothalamic hamartoblastoma cannot be reliably diagnosed as Pallister-Hall rather than another MCA syndrome, and, ultimately, the existence of Pallister-Hall syndrome could be questioned, as it could only be the extreme expression of one or several other syndromes. As this hypothesis cannot be proven or disproven at this point, the authors suggest creating the concept of multiplex phenotype. "Cerebro-Acro-Visceral Early lethality multiplex syndrome" is suggested to encompass all the ambiguous cases. Within this complex, an operative classification key is proposed. PMID- 1621757 TI - New multiple congenital anomalies: mental retardation syndrome (MCA/MR) with facio-cutaneous-skeletal involvement. AB - Five unrelated patients (a male and 4 females) were affected with a previously undefined multiple congenital anomalies/mental retardation syndrome which has been designated the facio-cutaneous-skeletal (FCS) syndrome and which includes mental retardation with specific sociable, humorous behavior, characteristic facial appearance, excessive generalized skin, postnatal growth failure, and skeletal involvement. Consanguinity was noted in 2 patients, thus autosomal recessive inheritance is suggested. PMID- 1621758 TI - Craniosynostosis associated with partial duplication of 15q and deletion of 2q. AB - We report on an infant with multiple congenital anomalies including complex craniosynostosis associated with an unbalanced karyotype, 46,XY, 2,+der(2),t(2;15)(q37;q26)pat. The previous report of a child with cloverleaf skull and partial duplication of 15q25----qter and the Man-on-Mouse Homology map suggests that a critical segment for synostosis of sutures may be in this region. PMID- 1621759 TI - Nail-patella syndrome in a spontaneously aborted 18-week fetus: ultrastructural and immunofluorescent study of the kidneys. AB - Nail-patella syndrome (NPS), hereditary onycho-osteodysplasia, is an autosomal dominant disorder of nail dystrophy, patellar absence or hypoplasia, incomplete elbow extension, conical posterior iliac horns, and nephropathy. We studied the kidneys of an 18-week spontaneously aborted fetus of a mother with the NPS. Ultrastructural examination of the kidney showed thickening of the capillary walls of the glomeruli and mesangium. There was irregular thickening of basement membranes with subendothelial fibrillar electron-dense deposits. Immunofluorescence showed fibrinogen deposition in glomerular basement membranes. Fibrinogen deposition in utero may ultimately lead to glomerular fibrosis and intrabasement membrane collagen deposition as seen in the adult renal lesion of this syndrome. This is the first report of the NPS in which the renal abnormalities have been studied in a fetus. These findings provide support for possible prenatal diagnosis of NPS by intra-uterine kidney biopsy. PMID- 1621760 TI - Trisomy 8: an additional case with unique manifestations [correction]. AB - We report on an infant with multiple congenital anomalies and mosaic trisomy 8 [corrected]. Clinical findings are presented, and compared with those of the 24 cases previously reported. Some unusual characteristics found in this patient include macrocephaly, an extreme degree of palatal hypoplasia, and abnormally shaped long bones. PMID- 1621761 TI - Interstitial deletion of 10q: clinical features and literature review. AB - We report on a patient with interstitial deletion of 10q and compare her to 8 previously described patients, 2 of whom have chromosomal breakpoints similar to our patient. Minor anomalies including broad forehead, hypertelorism, strabismus, prominent philtrum, and "dysplastic" pinnae are present in our patient. Psychomotor retardation and hypotonia are universal findings in 10q interstitial deletion. Growth retardation, not present in our patient, is seen in some. These clinical findings are sufficiently distinct to suggest early chromosome studies. PMID- 1621762 TI - Cervical spine in the Apert syndrome. AB - Radiographs of the cervical spine--in many cases longitudinal--were available for study in 68 cases of Apert syndrome. Autopsy material was available in one of these cases, and a 3-dimensional reconstruction from a CT scan was also studied in one case. Variable degrees of fusion were observed, involving the articular facets, the neural arch or transverse processes, or block fusion of the vertebral bodies. Ossification may not always be evident in some early radiographs. However, early radiographic signs of impending fusion may be irregularity in vertical orientation of the vertebral bodies and narrowing of the involved intervertebral spaces. Cervical fusions occurred in 68%, single fusions being found in 37%, and multiple fusions in 31%. C5-C6 fusion was most common, alone or in combination with other fusions. In contrast, cervical fusions are known to occur in 25% of Crouzon patients, most commonly involving C2-C3 only. It appears that when fusions are present, C5-C6 involvement in the Apert syndrome and C2-C3 involvement in the Crouzon syndrome separate the 2 conditions in most cases. Because cervical anomalies may complicate an already compromised airway in any form of acrocephalosyndactyly, it is imperative to initiate radiographic study of the cervical spine before undertaking anesthesia for surgery. PMID- 1621763 TI - Pigmentary dysplasias and chromosomal mosaicism: report of 9 cases. AB - Chromosomes were studied in 9 individuals with pigmentary dysplasias of the skin and other abnormalities. Of the 9 individuals, 5 were chromosomal mosaics in both blood lymphocytes and skin fibroblasts (46,XY/47,XY, + 13;46,XX/47,XX, + 14;46,XY/47,XY, + 18;46,XX/47,XX, + 18;46, XX/47,XX, + mar), while the other 4 individuals were chromosomally normal in both tissues studied. The pigmentary dysplasias involved hypo- or hyperpigmented patches/flecks or lines/whorls. The latter ran along Blachko lines on the back, abdomen and the limbs. These patterns varied not only between individuals but also between different regions of an individual. The possibility of chimerism was studied but ruled out (1/32 to 1/256) in 7 individuals, using chromosomal heteromorphisms in the patients and their parents as markers. PMID- 1621764 TI - Reciprocal translocation t(1;15)(p36.2;p11.2): confirmation of a suggestive cytogenetic diagnosis by in situ hybridization and clinical case report on resulting monosomy (1p). AB - A newborn girl with generalized muscular hypotonia and minor anomalies was referred for chromosome analysis. Cytogenetic investigation showed a satellite and an Ag-positive NOR on the distal short arm of one chromosome 1, thus indicating an unbalanced translocation involving the short arm of an acrocentric chromosome. The phenotypically normal mother had the same satellited chromosome 1 with Ag-positive NOR. One chromosome 15 was the only acrocentric chromosome in her karyotype lacking recognizable satellites and an Ag-positive NOR. Thus a balanced reciprocal translocation between the short arms of chromosomes 1 and 15 in the mother was suggested. The cytogenetic diagnosis was confirmed by nonradioactive in situ hybridization with the most distal DNA probe on chromosome 1, the probe p1-79, localized at chromosome band 1p36.3. The probe was biotinylated by nick-translation, and detection was done by FITC labelled avidin binding. Hybridization signals were observed on both the mother's normal chromosome 1 and the derivative chromosome 15 but not on her derivative chromosome 1. Consequently, the index patient has an unbalanced karyotype with monosomy (1p36.3). Comparing their clinical reports shows that patients with similar terminal deletions of 1p share several manifestations. PMID- 1621765 TI - Craniorachischisis totalis and sirenomelia. AB - We report on a male infant with craniorachischisis totalis and sirenomelia, an association that seems to have been observed only 5 times before. In addition to these anomalies, the patient had hypoplasia of the phalanges of the right thumb. The pattern of associated malformations in infants with anencephaly and sirenomelia is reviewed. This condition, which combines cephalic and caudal defects of the embryo, could be considered an example of the "axial mesodermal dysplasia spectrum" and may be related to the midline developmental field concept. PMID- 1621766 TI - Hans-Rudolf Wiedemann: an appreciation. PMID- 1621767 TI - Hans-Rudolf Wiedemann in a half century of German pediatric genetics. PMID- 1621768 TI - Two patients with chromosome 6q terminal deletions with breakpoints at q24.3 and q25.3. AB - We report on 2 patients with de novo terminal deletion of 6q. The first was a 4 month-old boy whose karyotype was 46,XY,del(6)(q24.3); the second a 2-year-old girl whose karyotype was 46, XX, del(6)(q25.3). The main anomalies in both patients included mental retardation, minor craniofacial and cerebral anomalies, and cardiac defects. The characteristic manifestations were imperforate anus in the first patient, and retinitis proliferans and a triatrial heart in the other. Comparison of clinical findings of our 2 patients with those of 18 previously reported patients with similar phenotypes suggests that terminal deletion of the 6q23 or 6q25 band is critical in producing the main anomalies of del(6q) syndrome. PMID- 1621769 TI - Paraplegia and congenital contractures as a consequence of intrauterine trauma. AB - We present a newborn infant with paraplegia and contractures of the lower limbs, consistent with neurologic injury rather than malformation. The mother was involved in a severe motor vehicle accident during the sixth month of pregnancy. We propose that this infant's injuries are a result of that accident. PMID- 1621770 TI - Trisomy 18 and a constitutional maternal translocation (2;18). AB - Parental chromosomes are usually not analyzed in cases of trisomy 18 because the extra 18 is assumed to have arisen through a meiotic nondisjunctional event. We report on a case of a trisomy 18 and a maternal translocation (2;18)(q34;q12). PMID- 1621771 TI - Familial aplasia cutis congenita and coarctation of the aorta. AB - We report on the association of aplasia cutis congenita (ACC) in the midline of the scalp vertex and coarctation of the aorta (CA) in mother and son. The acronym of ACCCA syndrome is proposed for this condition. Autosomal dominant inheritance is most commonly implicated in the familial cases of ACC. The familial aggregation of CA is attributed, in general, to a multi-factorial causation, with a few reported families suggesting autosomal dominant inheritance. The ACCCA syndrome could be due to a Mendelian mutation. PMID- 1621773 TI - Therapeutic index of pilocarpine, carbachol, and timolol with nasolacrimal occlusion. AB - We assessed the effect of nasolacrimal occlusion on the therapeutic index of various antiglaucoma medications in healthy volunteers and patients with glaucoma. Nasolacrimal occlusion used with pilocarpine 2% every 12 hours gave the maximal ocular hypotensive response. Carbachol 1.5% every 12 hours with nasolacrimal occlusion gave the maximal response for this drug. For timolol, nasolacrimal occlusion collapsed the dose-response curve and extended the duration of action. A final trial of carbachol added to timolol with nasolacrimal occlusion showed that timolol 0.25% and carbachol 1.5% every 12 hours gave the maximal response for this combination. Our findings suggest that most of the commercially used ocular hypotensive agents can achieve the same maximal effect with lower concentrations and less frequent administration (never exceeding every 12 hours) than are currently recommended should nasolacrimal occlusion be performed. Furthermore, nasolacrimal occlusion should markedly decrease the systemic absorption of topical ocular drugs and lessen the chance of systemic side effects. PMID- 1621772 TI - Albright hereditary osteodystrophy with hypothyroidism, normocalcemia, and normal Gs protein activity: a family presenting with congenital osteoma cutis. AB - The syndrome of Albright hereditary osteodystrophy (AHO), pseudohypoparathyroidism (PHP) and pseudopseudohypoparathyroidism (PPHP) is clinically and genetically heterogeneous. Classically, patients with PHP have the skeletal features of AHO, resistance to multiple hormones that work via cAMP such as parathyroid hormone and thyroid stimulating hormone, and deficient activity of Gs protein, the guanine nucleotide-binding protein that stimulates adenylate cyclase. However, patients without hormone resistance but with AHO and Gs deficiency were described (PPHP), as well as patients with multiple hormone resistance but without AHO or Gs deficiency. In a few patients with deficient Gs activity, hypothyroidism rather than hypocalcemia was the initial presentation of the disorder. We describe here a new variant of the syndrome, affecting 5 individuals in a 3 generation family with AHO, normal Gs activity and hypothyroidism. In the first 2 generations, mild features of AHO were present. The 2 sibs in the third generation had severe manifestations of AHO, including mild mental retardation as well as hypothyroidism. Diagnosis of congenital osteoma cutis at birth of the proband led to the diagnosis of the family. Elucidation of the molecular defect will shed light on the relationship between hormone resistance and AHO, as well as on the physiological mechanism of hormonal signal transduction. PMID- 1621774 TI - Ocular injuries caused by misuse of an immersion heater. PMID- 1621775 TI - Removable ligature during Molteno implant procedure. PMID- 1621777 TI - Localized distichiasis after tarsorrhaphy. PMID- 1621776 TI - Multifunction endolaser probe. PMID- 1621778 TI - Paroxysmal eyelid retractions. PMID- 1621779 TI - Position-dependent Parinaud's syndrome. PMID- 1621780 TI - Trabeculectomy without conjunctival incision. PMID- 1621781 TI - Argon laser gonioplasty in the treatment of angle-closure glaucoma. AB - We used argon laser gonioplasty to treat angle-closure glaucoma unrelieved by patent iridectomy. Laser energy (mean; 30 spots, 723 mW, and 0.2 second) was applied to the peripheral iris stroma to open the anterior chamber angle. Twenty of 32 eyes were successfully treated. After a median follow-up period of 18 months, 17 of these 20 successfully treated eyes (85%) had an intraocular pressure less than or equal to 19 mm Hg, and 19 of these 20 successfully treated eyes (95%) had an intraocular pressure less than or equal to 21 mm Hg. The 20 successfully treated eyes had a median duration of angle closure of 12 days. Twelve unsuccessfully treated eyes had a median duration of angle closure of 90 days. All successfully treated eyes had more than 50% of the treated angle opened by argon laser gonioplasty and all but three successfully treated eyes had more than three clock hours opened by argon laser gonioplasty. Argon laser gonioplasty may be successful in treating angle-closure glaucoma unrelieved by iridectomy, especially in cases that are recognized and treated soon after onset. PMID- 1621782 TI - Successful therapy for trilateral retinoblastoma. AB - Trilateral retinoblastoma, the intracranial malignancy associated with bilateral retinoblastoma, is an uncommon and clinically aggressive malignancy with a uniformly fatal outcome. Three children with newly diagnosed trilateral retinoblastoma were treated with systemic (cyclophosphamide and vincristine) and intrathecal (methotrexate, hydrocortisone, and cytarabine) chemotherapy, as well as craniospinal irradiation (one patient) in addition to therapy of the eye lesions. All three patients have had partial or complete response of the pineal tumors to chemotherapy, with no active disease eight or more years, 33 or more months, and 12 or more months, respectively, after diagnosis of the lesions. PMID- 1621783 TI - Hereditary microphthalmia with colobomatous cyst. AB - We examined five members of a highly inbred kinship who had isolated microphthalmia associated with colobomatous cysts and various other ocular lesions. They were all offspring of consanguineous (first cousins) and unaffected parents. Microphthalmia in this kindred was transmitted as an autosomal recessive trait. Ultrasonography was effective for prenatal diagnosis in two pregnancies at risk. PMID- 1621784 TI - A new, band-shaped and whorled microcystic dystrophy of the corneal epithelium. AB - Five family members and three unrelated patients (four women, four men, 23 to 71 years old) had a dystrophy of the corneal epithelium. Direct slit-lamp examination showed bilateral or unilateral, gray, band-shaped, and feathery opacities that sometimes appeared in whorled patterns. Retroillumination showed intraepithelial, densely crowded, clear microcysts. Light and electron microscopy disclosed diffuse vacuolization of the cytoplasm of epithelial cells in the affected area. Visual acuity was so reduced in three patients that abrasion of the corneal epithelium was performed. The corneal abnormalities recurred within months, with the same reduction in visual acuity as before. The corneal opacities were progressive in two patients but diminished noticeably in another after he began using a hard contact lens. We found no other ophthalmic irregularities or associated systemic abnormalities and no indication of drug-induced keratopathy. PMID- 1621785 TI - Corneal sensitivity after photorefractive keratectomy. AB - Corneal anesthesia or hypesthesia can complicate refractive surgical procedures such as epikeratophakia and radial keratotomy. An esthesiometer was used to measure the corneal sensitivity in unoperated-on corneas and fellow corneas after excimer laser photorefractive keratectomy. Decrease in corneal sensitivity was noted within six postoperative weeks, with mean sensitivity being 75.2% +/- 13.3% of normal. Within the first three postoperative months, the patients operated on for correction of compound astigmatism recovered 95.7% +/- 5.3% of the corneal sensitivity, whereas the patients operated on for correction of severe myopia recovered 86.2% +/- 11.2% (P = .07). None of the patients had delayed epithelial healing or recurrent corneal erosions during the time of decreased corneal sensitivity. In otherwise normal myopic eyes, photorefractive keratectomy measurably reduced corneal sensitivity for several postoperative weeks. PMID- 1621786 TI - Six cases of scleritis associated with systemic infection. AB - Isolated scleritis (without keratitis) associated with infections is uncommon, and correct diagnosis and appropriate therapy for it are often delayed. Six patients with infection-associated scleritis were seen at our institution between May 1983 and May 1990 (these patients represented 4.6% of all patients with scleritis [six of 130 patients] in that period). Three of these cases were associated with systemic infections. One was associated with syphilis, one was associated with tuberculosis, and one was associated with toxocariasis. Three cases resulted from local infections. One was associated with infection with Proteus mirabilis, one was associated with infection with herpes zoster virus, and one was associated with infection with Aspergillus. The Aspergillus infection developed after trauma and the P. mirabilis-induced infection developed after strabismus surgical procedures. Four of the six cases were initially misdiagnosed and inappropriately managed. Correct diagnosis was made seven days to four years after onset of symptoms. Review of systems, scleral biopsy, culture, and laboratory investigation were used to make the diagnosis. Differential diagnosis of scleritis must include infective agents. PMID- 1621787 TI - Visual outcome after penetrating keratoplasty with double continuous or combined interrupted and continuous suture wound closure. AB - We reviewed the consecutive records of 296 patients who underwent corneal transplantation at our institution to compare visual outcome between those who underwent double continuous suture wound closure and those who underwent a combination of interrupted and continuous suture wound closure. Of 156 patients on whom one of these closure techniques was performed, 33 patients satisfied our inclusion and exclusion criteria. Visual outcome between the two groups was compared at three, six, and 12 months. We found significant differences (P less than .05) in average corneal curvature and refractive spherical equivalents (steeper and more myopic, respectively, for double continuous suture wound closure); keratoscopic astigmatism, refractive cylindrical error; and average number of postoperative visits (greater for combined interrupted and continuous suture wound). Visual acuity without correction was significantly better at three months in the group that received double continuous sutures (P = .026). We found no marked difference in best-corrected visual acuity, frequency of graft rejection, requirement for contact lens fit, ratio of refracted vs potential visual acuity, or intraocular pressure. Patients who underwent double continuous suture closure had more rapid visual rehabilitation, had steeper corneas, and less astigmatism than patients who underwent the combined technique suture closure. PMID- 1621788 TI - Superior rectus muscle overaction after cataract extraction. AB - Four patients with an ipsilateral hypertropia after cataract extraction consistent with superior rectus muscle overaction were identified between March 1990 and April 1992. Operative trauma was the most likely causative factor, as other likely conditions were excluded. The proposed pathogenesis for all cases is similar to that of botulinum type-A toxin therapy: a transient postoperative weakness of the ipsilateral inferior rectur muscle leads to a contracture or strengthening of the ipsilateral antagonist (the superior rectus muscle). Possible mechanisms of injury that would result in a transient inferior rectus muscle palsy would include anesthetic myotoxicity or direct trauma to the muscle and related structures from the retrobulbar injection (or subconjunctival injection). Surgical intervention consisting of an ipsilateral superior rectus muscle recession and posterior fixation sutures (when the vertical incomitance was large) yielded excellent results in restoring single binocular vision. Possible preventive measures would include using a minimal volume of anesthetic along with careful needle placement. PMID- 1621789 TI - Therapeutic index of epinephrine and dipivefrin with nasolacrimal occlusion. AB - We assessed the effect of nasolacrimal occlusion on the therapeutic index of the adrenoreceptor agonists in healthy volunteers and patients with glaucoma. Nasolacrimal occlusion did not significantly alter the response to 2% epinephrine or to 0.1% dipivefrin in healthy subjects, suggesting that both 2% epinephrine and 0.1% dipivefrin are at the top of the dose-response curve. When 0.5% epinephrine with nasolacrimal occlusion was tested in patients with glaucoma, effects were noticeable at four and eight hours (P less than .05), but not at 12 hours. For 2% epinephrine, there was no significant difference at any measurement time. Epinephrine (1%) with and without nasolacrimal occlusion gave results similar to those of 2% epinephrine, suggesting that 1% epinephrine is also at the top of the dose-response curve. Nasolacrimal occlusion did not increase the ocular hypotensive effect of either of these concentrations. Because dipivefrin, the most widely used formulation in this class, is a prodrug of epinephrine that has a corneal penetration approximately 17 times that of epinephrine, 0.05% dipivefrin, every 12 hours, might be an adequate dosage for maximal effect. Although nasolacrimal occlusion did not alter the drug effect of 0.1% dipivefrin, preventing as much drug as possible from reaching the systemic circulation is desirable. PMID- 1621790 TI - Vitrectomy for perforating eye injuries from shotgun pellets. AB - Pars plana vitrectomy and scleral buckling were performed on 22 eyes of 19 patients for treatment of perforating eye injuries from shotgun pellets. We reviewed the intraoperative findings at the time of vitrectomy to determine what factors might influence final visual acuity. The presence of a total retinal detachment at vitrectomy portended a poor prognosis when compared with eyes without total retinal detachment, as only one of ten eyes with total retinal detachment obtained useful vision (P = .002). Preoperative separation of the posterior vitreous was associated with a favorable outcome when compared with the absence of posterior vitreous detachment (P = .035), as ten of 16 eyes with posterior vitreous detachment at the time of vitrectomy ultimately achieved functional vision. The locations of the exit wounds did not affect visual success in the overall series of patients. However, in the patients who achieved visual success, exit wounds outside the vascular arcades were more likely to be associated with final visual acuities of, or better than, 20/70 than were those within the arcades (P = .022). Other prognostic factors, such as the number of perforations and the use of cryotherapy, were also examined for their effects on final visual outcome. However, these factors did not appear to affect visual outcome statistically. PMID- 1621791 TI - Streptococcus viridans-induced crystalline keratopathy and fungal keratitis. PMID- 1621792 TI - Intraocular trauma from a microwave oven. PMID- 1621793 TI - Occupational therapy entry-level program applicants: a survey of northwest schools. AB - Recruitment of occupational therapy students requires both expansion and broadening of ethnic, cultural, age, sex, and geographic distribution. Information used to guide recruitment activities can be limited, quickly outdated, and regionally nonspecific. Applicants to all entry-level programs in the Northwest were surveyed to assess trends that could influence recruitment practices. One hundred thirty-five (82.8%) of the 163 applicants surveyed responded to a questionnaire that probed for sources of exposure to occupational therapy, career goals, and educational preferences. Applicants indicated having an initial interest in allied health or education fields, yet only 36% began college with occupational therapy education in mind. Volunteer or work experience in specific practice settings was identified by approximately 80% of the applicants as an influence in seeking an education in occupational therapy. Career influences, goals, and educational program preferences did not differ among applicants based on age, residential background, grades, or previous degree. An absence of applicants of ethnic minority allows limited application of findings to these targeted groups. PMID- 1621794 TI - Relaxation training: a self-help approach for children with headaches. AB - Children and adolescents frequently complain about recurrent nonmalignant headaches. Relaxation exercises are one possible treatment for these headaches. As the role of occupational therapy in pediatric pain management emerges, relaxation training is becoming one of the treatment activities. The present study investigated the efficacy of progressive relaxation exercises in reducing headache complaints, particularly those headaches of a mixed variety. Ten subjects with a mean age of 11.5 years completed the 6-week self-help program. A multiple-baseline across-subjects design was used. Baseline periods were randomly assigned and ranged from 7 to 25 days with treatment introduced in a time staggered fashion across subjects. After completing their treatment, 8 of the 10 subjects had a mean increase of 15% in headache-free days. Specific guidelines for relaxation training are provided in the outlined treatment program. PMID- 1621795 TI - A validity study of the posture and fine motor assessment of infants. AB - This study investigated the concurrent and construct validity of the Posture and Fine Motor Assessment of Infants (PFMAI) (Case-Smith, 1991). The subjects were 90 infants, 65 of whom were healthy and full-term and 25 of whom were premature and had medical risk factors. Concurrent validity was investigated through administration of the Peabody Developmental Motor Scales (Folio & Fewell, 1983) and the PFMAI (n = 25). Strong positive correlations resulted between the Peabody Gross Motor scale and PFMAI Posture scale and between the Peabody Fine Motor scale and PFMAI Fine Motor scale. Concurrent validity was also measured through correlation scores on the Bayley Scales of Infant Development (Bayley, 1969) with scores on the PFMAI. The correlations between the Bayley Motor scale and the PFMAI Posture scale and between the Bayley Mental scale and the PFMAI Fine Motor scale were high. Construct validity was estimated through an evaluation of how accurately the PFMAI discriminated between the premature subjects and the full term subjects. A discriminant analysis indicated that the PFMAI accurately classified 78% of the subjects as being either premature or full-term (i.e., 80% of the full-term subjects and 72% of the premature subjects). When the premature subjects were categorized as low-risk or high-risk according to their medical histories, the PFMAI accurately classified 66.7% of the total subject population as full-term, low-risk premature, or high-risk premature. These results indicate that the PFMAI has the adequate reliability and validity necessary for use as a clinical and a research instrument.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621796 TI - Comparison of performance in materials-based occupation, imagery-based occupation, and rote exercise in nursing home residents. AB - Materials-based occupation, imagery-based occupation, and rote exercise have been examined individually by several researchers. The present study compares all three approaches with one another (i.e., kicking a balloon, imagining kicking a balloon, and a control rote exercise) in nursing home residents. The dependent variable was the number of exercise repetitions. The subjects were 12 women and 3 men between 56 and 93 years of age residing in two nursing homes. All subjects experienced the three approaches but in different orders. One-way analysis of variance for related measures indicated a significant difference among conditions (p = .004). The Tukey procedure (Stevens, 1986) determined that the materials based occupation condition elicited significantly more repetitions than the other two conditions. The difference between the imagery-based occupation and rote exercise was not statistically significant. These findings support our profession's historical emphasis on the use of physical materials to enhance performance. PMID- 1621797 TI - Occupational therapists in private practice. AB - Although increasing numbers of occupational therapists are choosing to work in private practice, little data exist describing this sector of the profession. In the present study, experienced occupational therapists were asked about their moves into private practice, including (a) their motivation, (b) their preparation, and (c) their perceptions of the move's risks and benefits before and after the move. A survey was sent to a national random sample of 105 occupational therapists, 74 of whom responded. According to the survey, autonomy was the most important motivating factor for occupational therapists moving into private practice. However, once they were in private practice, the occupational therapists noted that increased income was a major benefit. These occupational therapists had planned for the risks of reimbursement, referral sources, and overhead but had not anticipated problems with staffing shortages. Incomes increased for occupational therapists who moved into private practice. The survey compared the incomes of occupational therapists before and after they entered private practice. It also compared their income and educational levels. Other comparisons included income and work experience, income and work role, and income and geographic location. Autonomy and financial considerations appear to be the overriding issues for occupational therapists choosing careers in private practice. Almost unanimously, the survey respondents said that private practice was a good career choice. PMID- 1621798 TI - Outcomes assessment and program evaluation: partners in intervention planning for the educational environment. AB - Accountability of educational institutions is a current trend in academia. Outcomes assessment provides a method of evaluating educational programs to ensure they are meeting their objectives. This paper presents an overview of outcomes assessment and describes its relationship to and integration with program evaluation. It also describes the implementation of an outcomes assessment program at Kean College of New Jersey, Union, New Jersey. A model for assessment within occupational therapy programs, which parallels a model for intervention planning, is introduced and discussed. PMID- 1621799 TI - Why students choose occupational therapy as a career. AB - To recruit students to occupational therapy, we need to know what prospective students seek in careers. A survey consisting of an attitude inventory was sent to 403 current occupational therapy students with a response rate of 54%. Earlier research identified that students had primarily altruistic goals in selecting occupational therapy as a profession, and this study continued to find that students wanted to help others; however, this was not a predictor of their favoring the profession. A factor analysis of the inventory revealed that students chose occupational therapy as a career because they liked the salaries, nationwide job availability, regular hours, and prestige that is associated with the profession. Students were more positive about the profession if they had experience working in occupational therapy departments, and 40% reported that no specific persons had influenced their career decision. PMID- 1621800 TI - Treatment choices: rehabilitation services used by patients with multiple personality disorder. AB - This article identifies mental health rehabilitation services for patients with multiple personality disorder. Through the use of a literature review and a retrospective examination of 20 patients' records, the frequency of discipline specific services is noted in occupational therapy, art therapy, movement therapy, vocational counseling, and recreational therapy. Recommendations for practice and program development include ongoing education about multiple personality disorder and continual assessment of the patient's functional level to identify subsequent treatment needs and services. PMID- 1621801 TI - Stability of the Jebsen-Taylor Hand Function Test across three test sessions. PMID- 1621802 TI - Views on physical agent modalities and specialization within occupational therapy: a rebuttal. PMID- 1621803 TI - Structuring education: development of the first educational standards in occupational therapy, 1917-1930. AB - The movement to standardize educational preparation in occupational therapy grew as the profession developed following World War I. This paper explores the debates that surrounded the evolution of occupational therapy's first sanctioned educational system. A variety of professionals involved in the formation of occupational therapy engaged in these debates. They focused their attention primarily on whether education should be regulated and, if so, how that education might be structured. Each coveted different views about how the fledgling profession might develop. These early debates signify one of the first attempts to identify a vision for the evolution of occupational therapy. PMID- 1621804 TI - Universities, accreditation, essentials, and the American Occupational Therapy Association. PMID- 1621805 TI - Specialization is not narrow. PMID- 1621806 TI - Regulation of glutamine metabolism in dog kidney cortex: effect of pH and chronic acidosis. AB - To examine the interrelationships of proton compartmentation and ammoniagenesis, experiments were performed in tubules and mitochondria isolated from dog kidney cortex. Tubules were incubated in Krebs-Henseleit buffer at different pH (pHe), and cytosolic pH (pHi) was estimated with the fluorescent probe 2',7'-bis(2 carboxyethyl)-5(6)-carboxyfluorescein. Mitochondrial pH (pHm) was determined simultaneously in intact tubules by use of dimethyloxazolidine-2,4-dione. Over the pHe range 6.9-7.7, pHi was similar in control and acidotic dogs and linearly related to pHe. At pHe 7.4 in control tubules. pHm was 7.78 +/- 0.07, and varied little over the pHe range of 7.0-7.7. The pH gradient across the mitochondrial membrane rose at acid pHe. pHm was more alkaline when estimated in tubules from acidotic dogs compared with controls. Ammonium and glucose productions from glutamine were inversely related to pHe and pHi in tubules from both control and acidotic animals and were higher in acidosis. In contrast, ammonium production by isolated mitochondria did not vary as pHe was altered. Enzyme fluxes, calculated from metabolite changes, demonstrated that glutamate dehydrogenase (GDH) flux was altered. Enzyme fluxes, calculated from metabolite changes, demonstrated that glutamate dehydrogenase (GDH) flux was inversely and glutaminase (PDG) flux was linearly related to pHe. Ammonium production was significantly greater in mitochondria from acidotic dogs because of accelerated flux through PDG but not GDH. The present study demonstrates significant difference between proton compartmentation and regulation of ammoniagenesis in kidneys from acidotic dog compared with rat. PMID- 1621807 TI - Increased distal nephron EGF content and altered distribution of peptide in compensatory renal hypertrophy. AB - Epidermal growth factor (EGF) precursor is synthesized within kidney in the thick ascending limbs of Henle's loop and in distal tubule. Under baseline conditions EGF precursor is localized to the luminal membrane. In contrast, functional EGF receptors are present in basolateral membranes of sensitive renal cells. Immunostainable EGF is increased in contralateral kidneys following uninephrectomy of rats. To confirm this increase and determine whether the distribution of EGF changes in this setting, we measured immunostainable EGF in kidneys originating from rats 1, 2, 5, or 14 days following unilateral nephrectomy or sham surgery. There was a suggestion of an increase in immunostainable EGF in distal tubules 5 days postnephrectomy and a definite increase 14 days postnephrectomy. At 1 or 2 days postnephrectomy, and following sham surgery, immunostainable EGF was present predominantly at luminal membranes. In contrast, immunostainable EGF was present more diffusely throughout distal tubular cells at 5 and 14 days postnephrectomy and clearly localized adjacent to both luminal and antiluminal membranes in kidneys obtained 14 days postnephrectomy. EGF extractable from kidneys was increased significantly 5 and 14 days postnephrectomy. This material is the size of mature EGF. The altered localization of immunostainable peptide indicates that a redistribution of intracellular EGF accompanies increased synthesis postnephrectomy. Antiluminal EGF precursor or mature EGF present within kidney could act as a paracrine growth factor. PMID- 1621808 TI - Substrate responses to acid-base alterations in dog renal proximal tubules. AB - Proximal tubules from dog kidney were incubated for 2-6 min with low concentrations of pyruvate, glutamine, and malate. When initial medium citrate was between 0 and 0.5 mM and alpha-ketoglutarate was between 0 and 0.1 mM, concentrations of these two substrates in tubules and media after incubation were lower with 10 than with 40 mM HCO3-. Malate levels in tubules and media changed in the opposite direction. CO2 formation from labeled citrate or alpha ketoglutarate was greater at low than at high HCO3-. In tubules treated with digitonin to disrupt the cell membrane, differences in citrate and alpha ketoglutarate concentrations in tubules at high and low HCO3- were eliminated. The effects of acid-base changes seen in intact tubules on malate levels and on the rate of oxidation of labeled citrate persisted after digitonin pretreatment. These results show that acute effects of acid-base changes on citrate, alpha ketoglutarate, and malate levels observed in intact renal cortex can be reproduced in isolated tubules. They suggest that these changes are related to changes in levels of citrate and alpha-ketoglutarate in cytoplasm without corresponding changes within mitochondria. PMID- 1621809 TI - Renal effects of endogenous prostaglandin synthesis promoter ONO-3122. AB - The renal effects of a prostaglandin synthesis agonist, 1-iodo-3-aminomethyl 5,6,7,8-tetrahydro-2-naphthol (ONO-3122), were investigated in anesthetized rats. ONO-3122 (0.3 mg/kg + 0.3 mg.kg-1.h-1 iv) doubled the urinary excretion of the main metabolites of prostaglandin F, and induced transient increases in renal blood flow and glomerular filtration rate (GFR) with a marked, stable natriuresis. Indomethacin suppressed the natriuresis. When the diuretic fluid losses were replaced, micropuncture showed an unaltered reabsorption of sodium in the proximal tubule but reductions in the loop of Henle (86 +/- 1 vs. 76 +/- 1%) and in the more distal segments (98 +/- 1 vs. 83 +/- 3%) with comparable reductions in water reabsorption. Potassium secretion was seen in the distal and collecting tubules. Without fluid replacement, sodium reabsorption was reduced in the loop and more distal nephron but increased in the proximal tubule. Differences between proximal and distal nephron GFR were unaffected by systemic ONO-3122. Loop perfusion with ONO-3122 did not change tubuloglomerular feedback responses, which were, however, completely suppressed by furosemide. It is concluded that ONO-3122 stimulates renal prostaglandin biosynthesis, transiently dilates renal vasculature, and induces natriuresis mainly by suppressing sodium and water reabsorption in the loop of Henle and the more distal nephron. Luminal ONO-3122 does not affect the tubuloglomerular feedback. PMID- 1621810 TI - Characteristics of osmolarity-stimulated urea transport in rat IMCD. AB - Urea transport across the terminal inner medullary collecting duct (IMCD) is mediated by a urea transporter that is stimulated by vasopressin (AVP) or hyperosmolarity. To determine whether hyperosmolarity stimulates urea transport by an adenylyl cyclase-dependent or -independent mechanism, terminal IMCDs were perfused with 10 microM forskolin followed by an increase in osmolality or with increasing osmolality followed by 10 nM AVP. In both protocols, stimulating adenylyl cyclase caused an additive increase in urea permeability (Purea) to that stimulated by hyperosmolarity. Next, we investigated whether hyperosmolarity stimulates the same urea transporter as AVP by studying the inhibitor profile and IMCD subsegment response of hyperosmolarity-stimulated urea transport and comparing it to properties already demonstrated for AVP-stimulated urea transport. In terminal IMCDs, luminal phloretin (250 microM) reversibly inhibited Purea by 63%. Thiourea (100 mM) inhibited Purea by 73% at two different levels of osmolality, 690 and 290 mosmol/kgH2O. The half-maximal inhibitory concentration (K1/2) for thiourea at 690 mosmol/kgH2O was not significantly different from the K1/2 value at 290 mosmol/kgH2O, suggesting that stimulation by hyperosmolarity is related to an increase in the Vmax for the urea transporter. Finally, we found that hyperosmolarity did not stimulate Purea in the initial IMCD. In summary, the data suggests that hyperosmolarity stimulates urea transport by an adenylyl cyclase-independent mechanism. However, the inhibitor profile and the IMCD subsegment response for hyperosmolarity-stimulated and AVP-stimulated Purea are similar, suggesting that both hyperosmolarity and AVP stimulate the same urea transporter. PMID- 1621811 TI - Role of paraventricular nucleus in control of blood pressure and drinking in rats. AB - The present investigation examined the abilities of angiotensin (ANG) II and III to produce increases in blood pressure and drinking when microinfused into the paraventricular nucleus (PVN) of the hypothalamus of the Sprague-Dawley rat. Dose dependent elevations in systemic blood pressure and heart rate were measured to both ANG II and III in the anesthetized rat, with ANG II more potent than ANG III at the two highest doses examined. Pretreatment with the specific ANG receptor antagonist [Sar1,Thr8]ANG II (sarthran), blocked subsequent ANG II- and III induced elevations in blood pressure, suggesting that these responses were dependent on the activation of ANG receptors. A similar analysis in awake rats yielded nearly equivalent results. A final experiment demonstrated that microinfusions of ANG II and III into the PVN produced drinking in a dose dependent manner, with greater consumption to ANG II than ANG III. Again, sarthran was found to block the dipsogenic response. Histological examination revealed that the location of the injection site was linked to the character of the ANG-dependent response. These data suggest that the PVN may play a critical role in mediating central ANG effects on body water homeostasis and blood pressure regulation. Furthermore, it appears that subnuclei of the PVN may participate differentially in ANG-mediated actions. PMID- 1621812 TI - Luminal influences on potassium secretion: chloride, sodium, and thiazide diuretics. AB - In the presence of Cl-, K+ secretion by the distal tubule saturates with increasing luminal Na+ concentration. Apparent maximal K+ secretion is attained with luminal Na+ concentrations of 40 mM. The results of the present study show that lowering the Cl- concentration of luminal fluid can increase the level of Na(+)-stimulated K+ secretion beyond the maximal level attained in the presence of Cl-. The effect of lowering luminal Cl- concentration to less than 10 mM on K+ secretion is greater with higher Na+ concentration. Under these conditions, chlorothiazide decreases K+ secretion. When chlorothiazide is present, changing the Na+ concentration does not affect K+ secretion. Because in rats a thiazide effect is attributed primarily to the distal convoluted tubule (DCT), we postulate that it is primarily DCT cells that increase K+ secretion when Na+ concentration is raised in the presence of low luminal Cl- concentration. We propose that the rat DCT cells have both an absorptive Na(+)-Cl- cotransport mechanism and a secretory K(+)-Cl- cotransport mechanism in the luminal membrane that can mediate the apparent exchange of Na+ for K+. PMID- 1621813 TI - Role of nucleoside uptake in renal postischemic ATP synthesis. AB - The role of nucleoside uptake in the enhanced metabolic recovery seen with postischemic ATP.MgCl2 was assessed by determining the effect of S-(p nitrobenzyl)-6-thioinosine (NBTI) on postischemic ATP recovery in rats given normal saline (NS), ATP.MgCl2, or adenosine after 45 min of bilateral renal ischemia. In NS-infused animals, postischemic administration of NBTI (250 nmol) had no significant effect on the pattern of ATP recovery. In animals given 50 mumol ATP.MgCl2, coinfusion of NBTI significantly reduced the renal ATP content 2 h after reperfusion but blocked only one-half of the enhancement in renal ATP content compared with animals given ATP.MgCl2 alone. In animals postischemically infused with [2,5,8-3H]ATP.MgCl2 (50 mumol) there was significant labeling of nucleotides, nucleosides, and bases after 2 h of reperfusion. The specific activity of the adenosine pool was consistent with significant label uptake in the form of adenosine. Coinfusion of NBTI led to a significant reduction in label incorporation into renal ATP and total adenine nucleotide pools. These data are consistent with an important role for an NBTI-sensitive nucleoside uptake mechanism in the enhanced metabolic and functional recovery observed in ischemically injured kidney treated by postischemic infusion of ATP.MgCl2. PMID- 1621814 TI - Cyclic nucleotides alter intracellular free Mg2+ in renal epithelial cells. AB - Intracellular Mg2+ plays an important role in cell physiology. Studies were performed on MDCK cells and primary cortical thick ascending limb (CTAL) cells to determine hormonal influences on intracellular Mg2+ control. Free Mg2+ ([Mg2+]i) was measured by fluorescence with mag-fura-2. Addition of 8-bromoguanosine 3',5' cyclic monophosphate (8-BrcG-MP, 10(-4) M) to subconfluent MDCK cells resulted in rapid increases in [Mg2+]i from basal levels of 552 +/- 6 microM to peak concentrations of 682 +/- 5 microM, whereas 8-BrcAMP (10(-4) M) led to significant decreases in [Mg2+]i from 538 +/- 5 to 362 +/- 17 microM. These effects of cyclic nucleotides were dose dependent with half-maximal concentrations (EC50) of approximately 10(-5) M for both increments in [Mg2+]i with cGMP and decrements in [Mg2+]i with cAMP. Atrial natriuretic peptide (ANP) and cGMP increased Mg2+ in porcine primary CTAL cells from 525 +/- 12 to 592 +/- 18 microM and from 538 +/- 8 to 609 +/- 18 microM, respectively. The increment in [Mg2+]i with ANP was dose responsive with EC50 values of approximately 10(-11) M suggesting that these effects may be of physiological importance. Parathyroid hormone and calcitonin and their second messenger, cAMP, diminished Mg2+ by approximately 80 microM. The EC50 value for calcitonin was in the order of 10(-9) M. The changes in [Mg2+]i, whether increases with ANP or cGMP and decreases with PTH, calcitonin, or cAMP, were rapid in nature and independent of changes in intracellular free Ca2+ concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621815 TI - cDNA cloning of a renal Na(+)-Ca2+ exchanger. AB - In the present study, the polymerase chain reaction (PCR) and library screening were used to clone a cDNA for a rabbit kidney Na(+)-Ca2+ exchanger on the basis of homology with the canine cardiac sarcolemmal sequence (D. A. Nicoll, S. Longoni, and K. D. Philipson. Science Wash. DC 250:562-565, 1990). There is a high degree of similarity between the two sequences, with nucleotide identities of 95, 89, and 90% in the hydrophobic membrane-associated domain, cytoplasmic domain, and 3'-untranslated region, respectively. The rabbit kidney cDNA encodes a predicted protein of 941 amino acids, 29 amino acids shorter than the canine sequence, with a relative molecular weight of 105,121. The deduced amino acid sequence is 96% identical in the membrane-associated domain and 94% identical in the cytoplasmic domain. Northern blot analysis reveals that the cDNA is expressed in the renal cortex. No expression is detected in the medulla. This result is in agreement with micropuncture studies that show Na(+)-Ca2+ exchanger activity in cortical but not medullary nephron segments. PMID- 1621816 TI - Glomerular basement membrane: in vitro studies of water and protein permeability. AB - The glomerular basement membrane (GBM) is an integral structural component of the glomerular filter, but its contribution to the hydraulic and macromolecular permeability properties of the glomerulus has been the subject of much controversy. We have modified previously reported methods to develop a technique with which to study filtration properties of microgram quantities of isolated GBM in vitro at physiological pressures. Rat glomeruli were sieved, and cells were removed with N-laurylsarcosine and DNase. GBM (150 micrograms; greater than 95% pure) were added to a mini-ultrafiltration cell and consolidated under pressure to form a continuous filter at the base of the cell. Water flux was identical to inulin clearance at applied pressures less than 150 mmHg and increased with progressive increments in the transmembrane pressure. Hydraulic conductivity of GBM was inversely related to the prevailing transmembrane pressure gradient. The hydraulic conductivity depended on albumin concentration in a manner that was not monotonic, with the conductivity being lower at 4 g/dl albumin than at 0 or 8 g/dl. When plasma was utilized as the retentate, the fractional clearance of albumin was over twice that of immunoglobulin G, and the fractional clearance of each protein was much higher than that in the intact glomerulus. On the basis of these results, both the hydraulic and macromolecular permeability of an individual layer of GBM are much greater than that reported for the intact glomerulus. The large quantitative differences between GBM permeability and that of intact glomeruli suggest a major contribution of cellular elements to glomerular permeability properties. PMID- 1621817 TI - Corticosterone 6 beta-hydroxylation correlates with blood pressure in spontaneously hypertensive rats. AB - Evidence for increased glucocorticoid 6 beta-hydroxylation (enhanced family 3A cytochrome P-450 activity) is found in certain reversible forms of human hypertension. This association was investigated in the spontaneously hypertensive rat (SHR). The proportion of injected [3H]corticosterone excreted in urine as 6 beta-[3H]OH-corticosterone was four- to fivefold higher in SHR than in control Wistar-Kyoto rats, before and after development of overt hypertension. Both hypertension and 6 beta-hydroxylation were inhibited by troleandomycin (a selective inhibitor of family 3A cytochromes P-450), consistent with a role for increased steroid 6 beta-hydroxylation in the genesis of hypertension in the SHR. PMID- 1621818 TI - Endothelium modulates renal blood flow but not autoregulation. AB - Inhibition of the production of the endothelium-derived relaxing factor (EDRF) nitric oxide using N omega-nitro-L-arginine methyl ester (L-NAME) increases blood pressure (BP) and decreases renal blood flow (RBF), suggesting that basal EDRF can modulate both systemic resistance and renal perfusion. We tested whether L NAME inhibition of EDRF could also change the autoregulation of RBF. Blood pressure and RBF were measured in Inactin-anesthetized Sprague-Dawley rats. A bolus of 10 mg/kg body wt of L-NAME produced the maximum pressor response (23 +/- 3 mmHg) and blocked acetylcholine-induced renal vasodilation. In control rats, sequential changes in renal perfusion pressure showed that RBF was well autoregulated down to 95 +/- 2 mmHg. L-NAME increased BP, decreased RBF by 33% (P less than 0.005), and increased renal vascular resistance twofold. Although RBF was decreased, the kidney was still able to autoregulate RBF, although reset around the lower flow. Acute hypertension by carotid occlusion and vagotomy increased BP by 26 +/- 6 mmHg (P less than 0.005) and slightly increased RBF, while autoregulation was maintained. The pressor response to L-NAME was amplified to 38 +/- 6 mmHg (P less than 0.001), but RBF decreased by 35% (P less than 0.01). Autoregulation of RBF was maintained, although reset around the lower flow. We conclude that, although endothelial EDRF production may help maintain RBF, it does not seem to mediate the intrinsic autoregulatory responses of the renal vasculature to altered renal perfusion pressure. PMID- 1621819 TI - Signal transduction events whereby PGF2 alpha inhibits the ammoniagenic response to acute acidosis. AB - Subconfluent cultures of LLC-PK1 cells were incubated for 1 h in Krebs-Henseleit buffer (KHB) of pH 7.4 or 6.8 to investigate the signal transduction events associated with prostaglandin F2 alpha (PGF2 alpha) inhibition of ammonia metabolism. Exposure of these cultures to PGF2 alpha (0.1 ng/ml) inhibited the acute low pH stimulation of ammonia production and to a lesser degree alanine formation in a manner analogous to the response exhibited with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Pretreatment with an inhibitor of protein kinase C [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, i.e., H-7] or utilization of cultures with downregulated protein kinase C activity abolished the inhibitory response to PGF2 alpha. Exposure to PGF2 alpha for 10 min in KHB of pH 6.8 resulted in an activation of protein kinase C, as demonstrated by a significant increase in membrane-bound enzyme activity. Incubation of the cells with PGF2 alpha in KHB of pH 6.8 also resulted in a significant increase in inositol trisphosphate formation. Treatment of the cultures with verapamil in calcium-containing medium or removal of calcium from the incubating medium resulted in a significant loss of the PGF2 alpha inhibitory response on both ammonia and alanine production. Furthermore, under conditions of calcium-free incubation, PGF2 alpha had no significant effect on protein kinase C activity. Because both PGF2 alpha- and TPA-induced inhibition of ammoniagenic response to acute acidosis was prevented by amiloride, the underlying mechanism may involve protein kinase C-mediated changes in intracellular pH. These results indicate that the activation of protein kinase C plays a key role in mediating PGF2 alpha inhibition of ammoniagenesis. PMID- 1621820 TI - Sequential changes in renal oxygen consumption and sodium transport during hyperdynamic sepsis in sheep. AB - The sequence of changes in systemic and renal oxygen delivery (QO2) and consumption (VO2) and renal function in an ovine model of progressive hyperdynamic sepsis was investigated. Nine chronically instrumented awake sheep were given a continuous intravenous Escherichia coli endotoxin infusion (20 ng.kg 1.min-1) for 3 days. After 8 h of the infusion, systemic arterial blood pressure and vascular resistance stayed decreased by 30% (P less than 0.001). Systemic QO2 progressively increased to a maximum of 157% of baseline values at 24 h and was associated with a decreased O2 extraction ratio from 33 +/- 2 (SE) to 23 +/- 2% (P less than 0.05), resulting in an unchanged systemic VO2. Renal blood flow and renal QO2 decreased by 40% during the first 12 h, returning to and staying at baseline values after 24 h. Renal VO2 decreased significantly by 35% at 12 h and then partially recovered to baseline values. Plasma creatinine clearance was maximally reduced to 25% of baseline values at 12 h and thereafter remained significantly (P less than 0.01) below 50% of baseline values. Both total and fractional sodium excretion fell at 12 h by 95 and 74%, respectively, and remained reduced over time, indicating conserved tubular function. The ratio of moles of sodium reabsorbed to moles of O2 consumed by the kidney was transiently reduced, from 33.4 +/- 4.1 to 12.4 +/- 3.6 at 12 h (P less than 0.05), indicating a relative increase in energy expenditure for tubular transport or renal synthetic activities, but recovered to baseline values after 24 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621821 TI - Dynamics of TGF-initiated nephron-nephron interactions in normotensive rats and SHR. AB - Proximal tubular pressure, glomerular filtration rate, and early distal tubule Cl oscillate at 35 mHz in normotensive rats because of tubuloglomerular feedback (TGF); the oscillation bifurcates to chaos in spontaneously hypertensive rats (SHR). To examine the importance of TGF-initiated vascular interactions between nephrons in these dynamics, we measured tubular pressure simultaneously in two or more nephrons. The oscillations were synchronized in nephrons supplied by a common cortical radial artery. The correlation coefficient of pressure records from coupled nephrons was 0.86 +/- 0.02. Intratubular furosemide perfusion diminished the oscillation in both the perfused and the coupled nephron; total autospectral power in each of the nephrons and cross-spectral power were reduced to 45% of control. The correlation between noncoupled nephrons was not significant, and intratubular furosemide perfused in one nephron had no effect on adjacent but noncoupled nephrons. In SHR, the correlation coefficient of tubular pressure records was high from coupled nephrons only; furosemide diminished the autospectral power of pressure fluctuations to approximately 60-75% of control in both perfused and coupled nephrons, and cross-spectral power was affected by a similar amount. Nephron-nephron interactions, specific to vascular connectivity, persist in SHR and appear to be stronger than in normotensive rats. PMID- 1621822 TI - Time course of renal glutamate dehydrogenase induction during NH4Cl loading in rats. AB - To study mechanisms involved in renal glutamate dehydrogenase (GDH) regulation in response to systemic acid loading, we have measured blood pH, ammonium excretion, renal GDH mRNA levels, and GDH activity in rats. Acid intake (0.28 M NH4Cl in drinking water for 3 days) increased GDH mRNA levels in the renal cortex, but had no effect in the outer stripe of the outer medulla, inner stripe of the outer medulla, or the inner medulla. Rats were subjected to a step change in acid intake by alkali loading for 3 days (7.2 meq NaHCO3 per day in food slurry) and shifting to acid loading for up to 7 days (7.2 meq NH4Cl in food slurry). Ammonium excretion rose rapidly, increasing by 14-fold in the first 24-h period and 38-fold in the second 24-h period. Cortical GDH mRNA levels were increased relative to alkali-loaded values by 3.7-fold in 24 h, 4.3-fold in 4 days, but only 2.2-fold in 7 days. GDH activity was unchanged after 24 h of acid intake, but was significantly increased after 48 h. We concluded the following: 1) GDH mRNA is present in all regions of the kidney, but levels increase in response to acid loading only in the renal cortex; 2) GDH mRNA levels increase within 1 day after the initiation of acid loading, but the associated increase in functional enzyme activity takes 2 or more days; and 3) the large increases in ammonium excretion that occur in the first day after initiation of acid loading are not dependent on increased GDH activity. PMID- 1621823 TI - Ca2+ signaling mechanisms of vascular endothelial cells and their role in oxidant induced endothelial cell dysfunction. AB - Endothelial cell function may be compromised in disease states as a result of oxidative injury, which may arise from a variety of sources. Oxidant stress appears to influence vascular reactivity and permeability via alteration in the production, release, or effect of endothelium-derived paracrine substances. An early event associated with endothelial cell dysfunction involves alteration in transmembrane signaling mechanisms. In particular, substantial evidence suggests that oxidant stress alters Ca2+ homeostatic mechanisms of the endothelial cell. Because an increase in the free cytosolic Ca2+ concentration ([Ca2+]i) of the endothelial cell is important for release of paracrine factors responsible for regulation of vascular tone and reactivity, oxidant stress-induced changes in Ca2+ signaling could explain much of the observed pathophysiology associated with oxidative injury. Under normal conditions, agonists such as bradykinin and ATP cause a biphasic increase in [Ca2+]i of the endothelial cell; an initial transient component reflects release of Ca2+ from internal stores, whereas a more long-lasting elevation in [Ca2+]i reflects Ca2+ influx from the extracellular space. After incubation with tert-butyl hydroperoxide, a time-dependent inhibition of the agonist-stimulated changes in [Ca2+]i is observed. The underlying molecular mechanisms associated with normal Ca2+ signaling and how these may be altered in the endothelial cell by oxidative stress is the subject of this review. PMID- 1621824 TI - Single perturbed beat vs. steady-state beats for assessing systolic function in the isolated heart. AB - Single-beat and steady-state techniques for evaluating end-systolic pressure volume relationship (ESPVR) and Frank-Starling mechanism (FSM) in the crystalloid perfused isolated rabbit heart were compared. In the single-beat technique, a train of stable isovolumic beats was interrupted with a single perturbed beat that either ejected against various levels of imposed isobaric load (ESPVR protocol) or beat isovolumically against various levels of end-diastolic volume (V(ED); FSM protocol). In steady-state technique, sustained beating was established, isobarically, at each of various loads (ESPVR protocol) or, isovolumically, at each of various V(ED) values (FSM protocol). ESPVR from steady state technique lay above and to the left of that from single-beat technique. Contractile state was not uniform within steady-state technique, whereas it was uniform within single-beat technique. In the FSM protocol, single-beat technique exhibited the following features relative to steady-state technique: 1) greater range of developed pressures, 2) steeper ascending limb and more sharply defined maxima, 3) higher maximal developed pressure (Pdmax), and 4) greater volume at Pdmax(Vmax). Again. a common contractile state existed within single-beat technique but not within steady-state technique. It was concluded that single beat technique was preferable to steady-state technique for evaluating ESPVR and FSM because 1) single-beat technique required less time for obtaining data, 2) single-beat technique allowed identification of uncomplicated values of Pdmax and Vmax, and 3) single-beat technique provided a common contractile-state reference for all data, whereas steady-state technique did not. PMID- 1621825 TI - Endothelial dysfunction of hindquarter resistance vessels in experimental heart failure. AB - Local vascular alterations may contribute to increased peripheral vasoconstriction in chronic heart failure. To test whether endothelial dysfunction might be involved, the effect of acetylcholine, nitroglycerin, and NG monomethyl-L-arginine (L-NMMA) was investigated in a constant-flow perfused hindquarter of rats with and without chronic heart failure (CHF) due to myocardial infarction. Changes in perfusion pressure were measured as an index of changes in hindlimb vascular resistance. The endothelium-dependent vasodilator effect of acetylcholine was significantly reduced in rats with large infarcts (greater than 40% of the left ventricle). However, the endothelium-independent vasodilator effect of nitroglycerin and the vasoconstrictor effect of L-NMMA were similar for infarct and normal animals. The vasodilator response to acetylcholine was partially inhibited by pretreatment with L-NMMA. Thus the basal release of nitric oxide from hindquarter resistance vessels is preserved in CHF. However, the endothelium-mediated dilation in response to acetylcholine is attenuated, in part, due to a depressed stimulated release of nitric oxide. The latter mechanism might be involved in the impaired vasodilatory capacity in the peripheral circulation in CHF, e.g., during exercise. PMID- 1621826 TI - Elevation of organ resistance due to leukocyte perfusion. AB - Leukocytes are larger and considerably less deformable than erythrocytes, thereby causing a disproportionate effect on local blood flow, which despite their low concentration, may be significant at the organ level. To investigate the degree to which circulating leukocytes affect whole organ resistance, a hemodynamically isolated rat gracilis muscle was perfused in situ under well-controlled conditions. Comparison of organ pressure-flow data from vasodilated vasculature using normal physiological cell concentrations and perfusion pressures indicates that leukocytes (60-75% neutrophils) provide approximately 22% of the whole blood resistance despite their relatively small cell volume fraction of approximately 0.1%. On a single cell basis, each leukocyte imposes a resistance elevation equivalent to that of approximately 750 erythrocytes. Furthermore, when leukocytes are activated via pretreatment using N-formyl-methionyl-leucyl phenylalanine or endotoxin, they show a higher resistance, accounting for 50-60% of the total resistance. These findings indicate that leukocytes play a significant role in normal skeletal muscle organ perfusion and may be a major determinant of organ perfusion during disease states. PMID- 1621827 TI - Endothelial modulation of porcine coronary microcirculation perfused via immature collaterals. AB - Porcine hearts have relatively few native collateral vessels and lack the propensity to develop normal perfusion to the collateral-dependent myocardium. To examine microvascular responses in the collateral-dependent region, collateral vessels were stimulated in pigs by the Ameroid constrictor technique. After 4-7 wk, isolated microarterial vessels (90-170 microns ID) were studied in a pressurized (40 mmHg), no-flow state. Microvessels from noninstrumented pigs were used as controls for vascular studies. Although myocardium in the collateral dependent region showed minimal evidence of infarction, percent systolic shortening was reduced at rest and after pacing compared with myocardium in the normally perfused region. Relaxations to the receptor-mediated endothelium dependent agents ADP and bradykinin were impaired in collateral-dependent coronary microvessels. Relaxations to the calcium ionophore A23187, which acts through a non-receptor-mediated mechanism, were similar in control and Ameroid microvessels. Relaxations to the endothelium-independent agent sodium nitroprusside were markedly enhanced in microvessels from the collateral dependent region compared with microvessels from control hearts. In conclusion, receptor-mediated endothelium-dependent relaxation is impaired and endothelium independent relaxation to sodium nitroprusside is enhanced in microvessels from myocardium perfused by immature collateral vessels. PMID- 1621828 TI - Different endothelial mechanisms involved in coronary responses to known vasodilators. AB - The role of the endothelium in mediating flow responses to acetylcholine (ACh), bradykinin (BK), adenosine (Ado), and the poorly hydrolyzable ATP-derivative beta,gamma-methylene-ATP (MeATP) was evaluated in the intact coronary system of the isolated perfused guinea pig heart. In the presence of superoxide anions, known to inactivate the endothelium-derived relaxing factor nitric oxide (NO), only steady-state dilatation induced by ACh (1 microM) was fully inhibited and that of BK (0.1 nM) attenuated. Similar effects were obtained with methylene blue and N omega-nitro-L-arginine; however, the latter also reduced the actions of Ado (0.1 microM) and MeATP (0.5 microM). Conversely, perfusion with the NO precursor L-arginine (10 microM) resulted in a potentiated relaxation by ACh, whereas steady-state responses to BK and Ado remained unchanged. Pretreatment of hearts with hydroxyl radicals (.OH) elevated vascular permeability. Under this condition, flow increases induced by ACh, BK, and Ado were enhanced by 130, 89, and 47%, respectively, whereas the effect of MeATP (0.5 microM) was reduced by 45%. Preexposure of hearts to the oxidant hypochlorous acid (HOCl) prevented dilatations by ACh, BK, MeATP and Ado (0.1 microM), and the response to Ado (5 microM) was reduced by 68%; postischemic hyperemia was attenuated. Glyburide, an inhibitor of ATP-sensitive K+ channels, halved the flow response to infused Ado (0.1 and 5 microM), inhibited MeATP, and abolished reactive hyperemia. We conclude that in the guinea pig coronary system ACh, BK, MeATP, and Ado (0.1 microM) induce endothelium-dependent vasodilatation, some step(s) of the signal transmission being vulnerable to oxidative attack by HOCl.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621829 TI - Effect of coronary stenosis on phasic pattern of septal artery in dogs. AB - To analyze the effect of coronary stenosis on the phasic pattern of blood flow velocity into the myocardium, we measured septal artery blood velocities under control conditions, i.e., no stenosis (N), with moderate (S1) and severe (S2) proximal coronary arterial stenosis, and during complete occlusion. In eight anesthetized open-chest dogs, the blood velocity measurements were performed using our 20-MHz multichannel pulsed Doppler method before and after intracoronary adenosine administration. Under N, the coronary perfusion pressure was set to approximately 100 mmHg, with S1 the poststenotic pressure was approximately 60 mmHg, and with S2 it was decreased to 35 mmHg. Septal arterial blood velocity area, which is the time-integrated envelope of the velocity, was divided into three components; systolic retrograde velocity area, systolic anterograde velocity area, and diastolic anterograde velocity area. There were no significant changes from N to S1 in any of the three velocity areas, which is a measure of the flow. Total inflow decreased from N to S2 by 52% (P less than 0.05). Diastolic anterograde flow decreased from N to S2 by 32% (P less than 0.05). Systolic retrograde flow increased from N to S2 by 75% (P less than 0.05). Systolic anterograde flow was almost unchanged by increasing stenosis. After complete occlusion, the septal artery exhibited a to-and-fro flow pattern. Adenosine-induced vasodilation reduced poststenotic pressure (P less than 0.05) and enhanced systolic retrograde flow without a significant increase in diastolic anterograde flow. Systolic retrograde flow increased at S1 by 49% (P less than 0.05) and at S2 by 27% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621830 TI - Effect of general anesthesia on cardiac vagal tone. AB - Although it is accepted that general anesthetics alter cardiac vagal tone, the magnitude of this effect was difficult to quantify by noninvasive methods until recently. Twenty-eight mongrel dogs were anesthetized using one of four representative anesthetics: pentobarbital sodium (25 mg/kg iv), morphine (1 mg/kg sc) with alpha-chloralose (50 mg/kg iv), urethan (500 mg/kg iv), thiopental sodium (25 mg/kg iv), and halothane (2% inhalation). Heart period (R-R interval) was recorded, from which the amplitude of the respiratory sinus arrhythmias (RSAs; frequency 0.24-1.04 Hz) was determined by time-series analysis. Morphine with alpha-chloralose-urethan significantly (P less than 0.01) increased RSA (control 8.3 +/- 0.6 ln ms2, anesthesia 9.4 +/- 0.3 ln ms2), whereas thiopental and halothane both significantly (P less than 0.01) decreased RSA (control 8.7 +/ 0.4 ln ms2, thiopental 1.3 +/- 0.4 ln ms2; and control 8.5 +/- 0.6 ln ms2, halothane 3.6 +/- 0.8 ln ms2). Pentobarbital failed to elicit a consistent change in RSA. These data suggest that vagal tone was maintained during morphine with alpha-chloralose-urethan anesthesia but was reduced during thiopental and halothane anesthesia. PMID- 1621831 TI - Restraining effect of intact pericardium during acute volume loading. AB - To determine the effect of the intact pericardium on ventricular end-diastolic pressures (EDP) during acute volume loading, we measured left ventricular (LV) and right ventricular (RV) micromanometer pressure and LV volume using a conductance catheter in eight open-chest, anesthetized dogs. A range of LV pressure and volume was obtained by intravascular volume expansion with the pericardium intact and then over a similar range after removal of the pericardium. Pericardial pressure (Pper) was calculated using static equilibrium analysis as the difference between LVEDP with the pericardium present and absent at a constant LV volume. At the beginning of the fluid infusion (LVEDP 7.3 +/- 1.7 mmHg and RVEDP 4.4 +/- 2.6 mmHg, mean +/- SD), Pper was not different from zero (-1.0 +/- 2.3 mmHg, P not significant). The onset of pericardial restraint (Pper greater than or equal to 0 mmHg) occurred when LVEDP was 9.1 +/- 2.9 mmHg and RVEDP was 4.1 +/- 2.9 mmHg. At low cardiac volumes before fluid infusion, RV transmural pressure was positive and significantly greater than the near zero Pper. After the onset of pericardial restraint, however, RVEDP and Pper increased similarly and were related according to Pper = 1.1 (+/- 0.34) RVEDP - 4.2 (+/- 2.6) mmHg, standard deviation 0.6 +/- 0.8 mmHg, r = 0.98 +/- 0.10. These data indicate that the intact pericardium behaves in two functionally distinct ways. At low cardiac volumes, Pper is zero and the pericardium does not affect LV filling. RV transmural pressure is positive and greater than Pper.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621832 TI - Comparable efficiencies of chemomechanical energy transduction between beating and fibrillating dog hearts. AB - We have recently proposed a mechanical index, equivalent pressure-volume (PV) area (ePVA), as a measure of the total mechanical energy during ventricular fibrillation (VF). ePVA, an analogue of the PV area (PVA) of a beating heart, is the area surrounded by the isobaric line drawn at the VF pressure, the end systolic and end-diastolic PV relations of the beating state. In the present study, using a closed-air chamber system, we actually produced isobaric contractions, PVAs of which were identical with ePVAs during VF. Myocardial O2 consumption (VO2) during VF was measured and compared with the estimated value from VO2 of isobaric contraction with identical PVA and equivalent heart rate (eHR). eHR, an estimate of the contraction frequency of each myocyte during VF, was determined from unloaded VO2 in beating and fibrillating states. The efficiency of the energy conversion from VO2 for mechanical purposes to the total mechanical energy (contractile efficiency) during VF was calculated as the reciprocal of the slope of the VO2-ePVA relation. The estimated VO2 during VF agreed with measured VO2 (r = 0.96, regression coefficient = 1.13). The slope of the VO2-ePVA relation during VF was not different from that in the beating state in all hearts by analysis of covariance, and mean contractile efficiency during VF (51 +/- 23%) was not significantly different from that in the beating state (40 +/- 12%). We conclude that 1) ePVA is considered to represent the total mechanical energy during VF, and 2) contractile efficiency during VF is comparable to that in the beating state. PMID- 1621833 TI - Pressure-maximal coronary flow relationship in regionally stunned porcine myocardium. AB - In view of variable results on maximal coronary blood flow in stunned myocardium, we studied the pressure-maximal coronary flow (PMCF) relationship in stunned myocardium in 12 anesthetized swine by using intracoronary adenosine (20 micrograms/kg). Subendocardial systolic segment shortening (SS) measured with sonomicrometry was 19 +/- 5% (means +/- SD) at baseline and 7 +/- 6% (P less than 0.01) at 30 min of reperfusion after 15 min of low-flow ischemia, at which time postsystolic shortening was present. Myocardial stunning increased the slope of the PMCF regression line (alpha PMCF) from 3.34 +/- 1.03 to 3.89 +/- 1.33 ml.min 1.mmHg-1 (P less than 0.01). Atrial pacing at 40 beats/min above spontaneous heart rate (n = 6) further reduced subendocardial SS to 6 +/- 6% (P less than 0.05). Dobutamine (4 micrograms.kg-1.min-1; n = 6) increased subendocardial SS to 13 +/- 5% (P less than 0.05) and abolished postsystolic shortening. Both interventions left alpha PMCF unchanged. In conclusion, myocardial stunning was associated with an increase in alpha PMCF that most likely resulted from the decreased contractile function. The absence of an effect of dobutamine may be due to its predominant action on diastolic function. PMID- 1621834 TI - Does systolic subepicardial perfusion come from retrograde subendocardial flow? AB - To examine the influence of cardiac contraction on systolic coronary flow and transmural blood flow distribution, we measured phasic blood flow velocity in distal extramural coronary arteries by Doppler velocimeter and regional myocardial blood flow by radiolabeled microspheres while the heart was beating and during prolonged diastoles in 12 dogs. A servo-controlled coronary perfusion circuit allowed mean coronary pressure to be selected and maintained during beating and diastolic conditions. In epicardial arteries just proximal to their entrance into the myocardium, blood flow was either negligible or reverse in direction during systole. When the heart was beating, subepicardial blood flow was 24.2 +/- 12.3% higher than during asystole (5.05 +/- 0.91 and 4.11 +/- 0.79 ml.min-1.g-1 for beating and prolonged diastoles, respectively; P less than 0.01). In the subendocardium, flow was 49.8 +/- 14.7% lower in the beating condition than during prolonged diastoles (4.23 +/- 1.46 and 8.26 +/- 1.71 ml.min 1.g-1 for beating and asystole, respectively; P less than 0.01). When heart rate was increased stepwise from 60 to 150 beats/min, subendocardial flow fell approximately linearly; flow to the superficial layer was relatively unaffected. In beating hearts, lowering mean left main coronary artery (LMCA) pressure from 80 to 50 mmHg resulted in more systolic reverse flow and a fall in inner-to-outer flow ratio from 0.82 +/- 0.18 to 0.66 +/- 0.34 (P less than 0.05). Because mean LMCA pressure was held constant when the heart was stopped, differences in regional blood flow between beating and diastolic conditions were primarily due to cardiac contraction. Because little or no blood entered the myocardium from the extramural arteries during systole, we conclude that the decrease in subendocardial flow and the increase in subepicardial flow were caused by retrograde pumping of blood from the deep layer to the superficial layer of the left ventricle. Systolic retrograde flow to the subepicardium may help explain this layer's relative protection from ischemia. PMID- 1621835 TI - Cellular mechanisms of ventricular failure: myocyte kinetics and geometry with age. AB - To determine whether heart failure is a consequence of alterations in cardiac cellular performance, myocytes were isolated from Fischer 344 rats at 4, 12, 20, and 29 mo of age and studied mechanically and morphometrically. Left ventricular myocyte length increased by 14.5, 14.4, and 24.0% at 12, 20, and 29 mo when compared with 4-mo-old animals. An 11.4 and 14.2% increase in length was seen for right ventricular myocytes from 4 to 12 mo and from 20 to 29 mo, respectively. Although no change in cell width was seen in either ventricle as a function of age, myocardial cells were more irregular in shape and consistently longer in the left ventricle at 20 and 29 mo. Left myocytes at 29 mo revealed diminished velocities of shortening (31.7%) and relengthening (59.5%). Contraction duration increased due to a 28.9% prolongation of time to peak shortening and a 26.5% increase in time to relengthening, resulting in a 25.8% decrease in myocyte shortening at 29 mo. Similar changes were observed in right ventricular myocytes, but they occurred later in life. Thus the alterations in myocyte geometry and depression in contractile performance seen here are major contributors to the eccentric dilated ventricular chamber and diminished pump function previously documented in the age-related transition from normal cardiac dynamics to left ventricular dysfunction and failure. PMID- 1621836 TI - Effects of endothelin on resistance arteries of DOCA-salt hypertensive rats. AB - The effect of endothelin (ET)-1 was investigated on resistance arteries of less than 300-microns lumen diameter from the mesenteric circulation, mounted on a wire myograph, in deoxycorticosterone acetate (DOCA)-salt hypertensive rats within 2 wk of developing hypertension and in uninephrectomized controls. Arteries from DOCA-salt hypertensive rats presented a significantly reduced external and lumen diameter and increased media width and wall cross-sectional area. Vessels from DOCA-salt hypertensive rats responded to ET-1 with lower active wall tension and media stress. Because the lumen diameter was significantly decreased in DOCA-salt hypertensive rats, the active pressure developed in response to ET-1 was similar in both groups. In contrast, the maximal tension response to arginine vasopressin was enhanced in DOCA-salt hypertensive rats. The sensitivity to both peptides and norepinephrine (NE) was similar in both groups. After removal of endothelium by exposure to the nonionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, ET-1 elicited tension responses that were also lower in DOCA-salt hypertensive rats, whereas NE responses were similar in both groups. These results demonstrate significant morphological and functional changes in small arteries of DOCA-salt hypertensive rats within 2 wk of developing hypertension and blunted reactivity to ET-1. Because similar results were found after removal of endothelium, it is likely that neither prior receptor occupation by endogenous ET nor acute effects of other endothelial cell products play a role in the reduced responsiveness to ET of vascular smooth muscle of small resistance arteries of DOCA-salt hypertensive rats. PMID- 1621837 TI - Transforming growth factor-beta 1 inhibits L-arginine-derived relaxing factor(s) from smooth muscle cells. AB - The effects of human recombinant interleukin-1 beta were investigated on the release of nonprostanoid relaxing substances from cultured aortic smooth muscle cells from Wistar rats. Cells cultured on microcarrier beads were packed in columns. The perfusate over these beads was bioassayed by measuring changes in isometric tension of contracted arteries without endothelium. The perfusates from interleukin-1 beta-treated smooth muscle cells, but not from control cells, evoked relaxations. The relaxations persisted when the transit time between the cultured smooth muscle cells and the detector was increased to 5 min. The effect of relaxing substance(s) was inhibited by cycloheximide, nitro-L-arginine, methylene blue, and transforming growth factor-beta 1. L-Arginine but not D arginine overcame the blockade by nitro-L-arginine. Superoxide dismutase potentiated the relaxations. In cells cultured in multiwell plates, interleukin-1 beta evoked a time- and concentration-dependent accumulation of nitrite in the extracellular medium that was inhibited dose dependently by transforming growth factor-beta 1. These studies demonstrate that cultured smooth muscle cells can be stimulated to produce nitric oxide-related substances and that the inducible pathway is modulated by transforming growth factor-beta 1. PMID- 1621838 TI - Effect of exogenous fatty acids on reperfusion arrhythmias in isolated working perfused hearts. AB - Exogenous fatty acids may promote arrhythmias during ischemia and reperfusion, perhaps by increasing myocardial concentrations of long-chain acylcarnitines. We therefore studied the effects of high concentrations of fatty acids on reperfusion arrhythmias and acylcarnitine accumulation in isolated working rat hearts subjected to regional ischemia and reperfusion. Hearts were perfused with buffer containing 3% albumin, 5.9 mM K+, and either 11 mM glucose or 11 mM glucose plus 1.2 mM palmitate. After 15 min of aerobic work, the left anterior descending artery was reversibly ligated for 10 min and released, and the hearts were subsequently reperfused for 3 min. Although ischemic zone acylcarnitine accumulation after reperfusion was significantly greater in glucose plus palmitate-perfused hearts (247 +/- 149 vs. 717 +/- 176 nmol/g dry wt in glucose- vs. palmitate-perfused hearts, respectively), no significant differences in the incidence (67 vs. 44%) or duration (95 +/- 17 vs. 56 +/- 17 s) of ventricular fibrillation (VF) were seen in glucose or glucose plus palmitate hearts, respectively. Because low K+ concentration ([K+]) has been reported to increase reperfusion arrhythmias in similar models, we reduced perfusate [K+] to 4.0 mM. This significantly increased the incidence and duration of VF in hearts perfused with glucose alone but had no effect in palmitate-perfused hearts. We conclude that acylcarnitine accumulation is not arrhythmogenic in this model and that fatty acids may actually have antiarrhythmic effects if exogenous [K+] is low. PMID- 1621839 TI - Hemodynamic studies in DOCA-salt hypertensive rats after opening of an arteriovenous fistula. AB - We determined the cardiovascular responses in normal and deoxycorticosterone acetate (DOCA)-salt hypertensive rats with reduced total peripheral resistance due to an arteriovenous (a-v) fistula. Animals were divided into four groups: control, fistula, DOCA-salt, and DOCA-salt fistula. The fistula was made by anastomosing the aorta and vena cava below the renal arteries. Four weeks after the creation of the fistula both DOCA-salt and DOCA-salt fistula animals received DOCA and salt for 6-8 wk. At the end of 10-12 wk we measured mean arterial pressure, cardiac output, tissue flows, and right atrial pressure. Flow measurements using radioactive microspheres were made in anesthetized animals. Cardiac index (CI) was 202% higher in the fistula group than in the control animals and 165% higher in the DOCA-salt fistula than in the DOCA-salt animals. There was no difference in cardiac output between the control and DOCA-salt animals. The increase in cardiac output was due to the fistula flow as evidenced by a significant increase in the number of microspheres in the lung. Mean arterial pressure was 115 +/- 4 mmHg (control) and 108 +/- 5 mmHg (fistula) in non-DOCA rats but increased in both DOCA groups, 159 +/- 3 mmHg (DOCA-salt) and 145 +/- 5 mmHg (DOCA-salt fistula). Right atrial pressure was increased above control in both fistula animals but was normal in DOCA-salt animals. Total peripheral resistance (TPR) was higher than control in DOCA-salt animals, but TPR in both the fistula and DOCA-salt fistula animals was lower than control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621840 TI - Kidney cross transplants in Dahl salt-sensitive and salt-resistant rats. AB - Previous kidney cross-transplant studies have demonstrated that the genotype of the kidney plays a role in determining the blood pressure of the recipient in Dahl salt-sensitive (S) and salt-resistant (R) rats. The present studies were designed to elucidate this role. Kidney cross transplants were performed in unilaterally nephrectomized male recipients (John Rapp strains), such that each rat had a native kidney and a transplanted kidney of the opposite genotype. S and R rats with a native kidney and a transplanted kidney of the same genotype served as controls. After 4 wk on a 7.8% NaCl diet, rats were anesthetized and renal clearance studies were performed. S kidneys had lower glomerular filtration rate (GFR) and renal plasma flow (RPF) than R kidneys, and these differences were determined by the kidney's genotype rather than the recipient's, since S kidneys in R recipients tended to have lower GFR and RPF than R kidneys in S recipients. In contrast, independent of the kidney's genotype, the kidneys in S rats tended to have higher fractional excretion of H2O and Na (FEH2O and FENa) than the kidneys in R rats. Thus there were genetically determined differences in renal function between S and R rats; some (RPF and GFR) were intrinsic to the kidney, whereas others (FEH2O and FENa) were intrinsic to the host.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621841 TI - Mechanism of impaired energy metabolism during acidosis: role of oxidative metabolism. AB - Isolated perfused rat hearts were used to study the effects of metabolic acidosis on energy metabolism. Hearts perfused with different substrates (glucose, pyruvate, and succinate) were subjected to metabolic acidosis. With all substrates, there were comparable decrements in oxygen consumption (approximately 35%), cardiac function (decrease in first derivative of pressure of 65%), and similar changes in high-energy phosphates (approximately 150% increases in inorganic phosphate and 25% decreases in phosphocreatine concentrations) with metabolic acidosis. To further investigate the metabolic effects of acidosis, isolated cardiac mitochondria were exposed to different incubation media pH conditions and given simple metabolites (glutamate/malate, succinate, or pyruvate) or fatty acids (octanoate). Reduction of incubation media pH to 6.0 did not significantly affect either coupled respiration rate or the respiratory control ratio (RCR) with any substrate. These data suggest that metabolic acidosis induces decreases in energy production in the isolated perfused heart by inhibiting mitochondrial substrate utilization and not by impairing glycolysis. However, this impairment of mitochondrial function is not a direct effect of acidosis itself but appears to occur secondarily to some other effects of acidosis which are, as yet, incompletely understood. PMID- 1621842 TI - Endotoxin impairs flow-induced vasodilation of porcine coronary arterioles. AB - The purpose of this study was to test the hypothesis that endotoxemia impairs endothelium-dependent (both receptor-mediated and flow-induced) vasodilation in porcine coronary arterioles. Coronary arterioles were isolated from three groups of 4- to 8-wk old (10.3 +/- 0.8 kg) pigs: endotoxemic (E; 250 micrograms/kg endotoxin iv), control (C; equal volume of saline), and untreated pigs (UT). Subepicardial arterioles (60-120 microns) were isolated and cannulated with two micropipettes that were connected to two independent reservoir systems. Intraluminal pressure was set at 60 cmH2O throughout the experiments. All C vessels developed spontaneous tone and exhibited flow-induced vasodilation from 65 to 95% maximal diameter. Spontaneous tone developed in only three of five arterioles from E pigs, and flow-induced vasodilation was not observed in any arteriole from E pigs. Spontaneous tone developed in all six arterioles isolated from UT pigs but disappeared in four of these vessels as a result of 1 h of in vitro incubation with endotoxin (2.5 micrograms/ml). Flow-induced vasodilation was also abolished in these vessels after 1 h of endotoxin exposure. Incubation with 3 mM L-arginine, in vitro, restored flow-induced vasodilation in E arterioles and endotoxin-treated UT arterioles. Vasoconstriction induced by acetylcholine (ACh) and vasodilation induced by nitroprusside (NP) and bradykinin (BK) were similar in arterioles from all groups. In contrast, endotoxin impairs flow-induced vasodilation of coronary arterioles. The mechanism responsible for the impairment of flow-induced vasodilation seems to reside in disruption of the L-arginine/nitric oxide pathway. PMID- 1621843 TI - Training effects on the regional blood flow response to exercise in myocardial infarcted rats. AB - The regional blood flow (BF) response to submaximal exercise was determined for sedentary and trained myocardial infarcted (MI) rats. Training consisted of treadmill running (10% grade, 30 m/min) for 1 h/day, 5 days/wk for 12-14 wk and produced decreases in resting heart rate and increases in maximal O2 uptake and endurance capacity. BF determined at 2 and 6 min of exercise (via radiolabeled microspheres) demonstrated that trained rats maintained greater BF to organs found in the abdominal region when compared with their sedentary counterparts. BF to the total hindlimb musculature at 2 min of exercise was greater in sedentary rats when compared with their trained counterparts and was the consequence of greater BF to 10 of the 27 muscle or muscle parts investigated. At 6 min of exercise, BF to the total hindlimb musculature was similar between trained and sedentary rats, as BF in 9 of 27 muscles or muscle parts investigated decreased from 2 to 6 min of exercise for the sedentary group. In general, the BF patterns within and among the individual muscles of the hindlimb were different between the two groups. Trained rats tended to maintain greater BF to the predominantly red muscles, whereas the sedentary rats maintained greater BF to the predominantly white muscles at 6 min of exercise. In conclusion, the training induced changes in BF found in this study are similar to those found previously for normal rats, and they demonstrate that endurance training produces changes in the regional distribution of BF during exercise in MI rats. PMID- 1621844 TI - Interaction of lysophosphatidylcholine with aortic endothelial cells. AB - To better understand the vascular actions of lysophosphatidylcholine (lysoPC), we studied the interaction of [1-14C]palmitate-labeled lysoPC with bovine aortic endothelial cells. These cells took up lysoPC from media containing albumin, low density lipoproteins (LDL), or acetyl-LDL. Uptake occurred faster than conversion to phosphatidylcholine (PC), leading to some lysoPC accumulation in endothelial lipids. Endothelial cell monolayers grown on micropore filters took up lysoPC from both apical and basolateral surfaces, preventing substantial amounts from passage across the endothelial monolayer. However, lysoPC present in the interstitial medium of an endothelial-smooth muscle coculture was incorporated primarily by the smooth muscle cells. Endothelial cells grown on filters released lysoPC into both the apical and basolateral medium in the presence of albumin or lipoproteins. Exposure to 50 microM lysoPC produced no evidence of endothelial cytotoxicity, but prostaglandin (PG)I2 production was reduced. These studies suggest that the endothelium can participate in the processing of circulating lysoPC and, through basolateral uptake, can facilitate the removal of lysoPC formed within the arterial wall. By decreasing PGI2 output, however, exposure to high concentrations of lysoPC may reduce the antithrombotic and vasodilator capacity of the endothelium. PMID- 1621845 TI - Effects of chronic hypoxia on capillary flow and hematocrit in rat skeletal muscle. AB - The cremasteric microcirculation was studied in rats exposed to chronic hypoxia. Control male weanling Sprague-Dawley rats (n = 8) were raised for 42-49 days at 752 mmHg. Hypoxic rats (n = 9) were reared for 3 days at 551 mmHg, 4 days at 461 mmHg, 3 days at 371 mmHg, and 31-38 days at 311 mmHg (6,000 m). Red blood cells labeled with fluorescein isothiocyanate were injected. The exposed cremaster was observed using fluorescence microscopy. Rats acutely breathed 10, 21, and 30% O2 spontaneously in random order. Hypoxia-adapted animals had greater (P less than 0.01) red cell flux (10.6 +/- 1.0 vs. 5.7 +/- 0.4/s), capillary hematocrits, capillary-to-systemic hematocrit ratios (0.42 +/- 0.02 vs. 0.33 +/- 0.02), and reduced red cell spacing (11.4 +/- 1.3 vs. 22.3 +/- 2.0 microns) than controls under 21% O2. Chronically hypoxic rats also demonstrated significantly (P less than 0.05) larger capillary diameters (6.52 +/- 0.04 vs. 6.15 +/- 0.06 microns) and greater perfused (135 +/- 5 vs. 94 +/- 3 mm/mm3) and anatomic (182 +/- 5 vs. 151 +/- 8 mm/mm3) microvessel length-densities at 21% O2. Results were generally similar for 10 and 30% O2. Bulk capillary blood flow was significantly (P less than 0.01) greater in controls (2.75 +/- 0.32 vs. 1.87 +/- 0.12 pl/s) only under 30% O2. Our experiments demonstrate that numerous physiological, in addition to anatomic, alterations can occur in the cremasteric microcirculation in response to chronic hypoxia. PMID- 1621846 TI - Beat-to-beat changes in AV nodal refractory and recovery properties during Wenckebach cycles. AB - The roles of changes in refractory and recovery properties of the atrioventricular node as affected by facilitation and fatigue in the genesis of Wenckebach periodicity were studied in isolated rabbit heart preparations. The contribution of nodal recovery time, facilitation, and fatigue to beat-to-beat changes in nodal conduction time (NCT) and effective (ERPN) and functional refractory periods of node (FRPN) occurring during stable 4:3 Wenckebach cycles was determined with premature stimulation protocols performed during these cycles. Fatigue prolonged, equally for each beat, NCT, ERPN, and FRPN, and therefore did not contribute to Wenckebach periodicity. Beat-to-beat increases in facilitation broadened the range of recovery times for which conduction was successful and decreased NCT, ERPN, and FRPN below the values expected from fatigue alone. However, ERPN and NCT increased overall from beat to beat because of NCT-induced (effects of NCT on ensuing refractoriness) increases in nodal refractoriness and consequent shortenings of the recovery time. These findings establish a complementary role for the recovery and refractory properties in generating the Wenckebach periodicity and demonstrate the modulating roles of facilitation and fatigue on this phenomenon. PMID- 1621847 TI - Effects of graded hypotension on cerebral blood flow, blood volume, and mean transit time in dogs. AB - This study tested the hypothesis that cerebral blood flow (CBF) is maintained by vasodilation, which manifests itself as a progressive increase in mean transit time (MTT) and cerebral blood volume (CBV) when cerebral perfusion pressure is reduced. Cerebral perfusion pressure was decreased in 10 pentobarbital anesthetized dogs by controlled hemorrhage. Microsphere-determined CBF was autoregulated in all tested cerebral regions over the 40- to 130-mmHg cerebral perfusion pressure range but decreased by 50% at approximately 30 mmHg. MTT and CBV progressively and proportionately increased in the right parietal cerebral cortex over the 40- to 130-mmHg cerebral perfusion pressure range. Total hemoglobin content (Hb1), measured in the same area by an optical method, increased in parallel with the increases in CBV computed as the (CBF.MTT) product. At 30 mmHg cerebral perfusion pressure, CBV and Hb were still increased and MTT was disproportionately lengthened (690% of control). We conclude that within the autoregulatory range, CBF constancy is maintained by both increased CBV and MTT. Outside the autoregulatory range, substantial prolongation of the MTT occurs. When CBV is maximal, further reductions in cerebral perfusion pressure produce disproportionate increases in MTT that signal the loss of cerebral vascular dilatory hemodynamic reserve. PMID- 1621848 TI - Mathematical modeling of human cardiovascular system for simulation of orthostatic response. AB - This paper deals with the short-term response of the human cardiovascular system to orthostatic stresses in the context of developing a mathematical model of the overall system. It discusses the physiological issues involved and how these issues have been handled in published cardiovascular models for simulation of orthostatic response. Most of the models are stimulus specific with no demonstrated capability for simulating the responses to orthostatic stimuli of different types. A comprehensive model incorporating all known phenomena related to cardiovascular regulation would greatly help to interpret the various orthostatic responses of the system in a consistent manner and to understand the interactions among its elements. This paper provides a framework for future efforts in mathematical modeling of the entire cardiovascular system. PMID- 1621849 TI - Cardiac microdialysis in isolated rat hearts: interstitial purine metabolites during ischemia. AB - Cardiac microdialysis is a recently developed technique that allows intramyocardial interstitial fluid (ISF) to be sampled via the implantation and perfusion of a small, hollow dialysis fiber within the myocardium. The purpose of this paper is to describe initial studies using cardiac microdialysis in the isolated perfused heart. Microdialysis probes, constructed in the laboratory, were implanted in the left ventricular myocardium of isolated perfused rat hearts and perfused at 0.5 microliter/min with Krebs-Henseleit buffer. The effluent dialysate, assayed for adenosine, inosine, hypoxanthine, xanthine, and uric acid, was used as an index of intramyocardial levels of these purine metabolites. All metabolites were elevated initially after implantation, declined rapidly in the first 45 min, and were then stable for the next 90 min. Based on in vitro percent recovery data, baseline dialysate concentrations were extrapolated to yield estimates of intramyocardial ISF (in microM) 0.47 adenosine, 0.85 inosine, 0.29 hypoxanthine, 0.49 xanthine, and 8.6 uric acid. During global zero-flow ischemia (37 degrees C), dialysate levels of all purine metabolites were elevated, with inosine being the predominant compound. Pretreatment of the hearts with 50 microM erythro-9-(2-hydroxy-3-nonyl)adenine, an adenosine deaminase inhibitor, markedly enhanced ISF adenosine accumulation and attenuated the accumulation of inosine, hypoxanthine, and xanthine. The simplicity and versatility of cardiac microdialysis in the isolated perfused heart suggest that this technique may be a valuable adjunct to the many studies performed using this preparation. PMID- 1621850 TI - Simple circuit for pacing hearts of experimental animals. AB - In this paper we describe a simple pacing circuit which can be used to drive the heart over a wide range of rates. The circuit is an astable multivibrator, based on an LM555 integrated circuit. It is powered by a 9-V battery and is small enough for use in rabbits. The circuit is easily constructed and inexpensive, making it attractive for numerous applications in cardiovascular research. PMID- 1621851 TI - Novel technique to load indo-1 free acid into single adult cardiac myocytes to assess cytosolic Ca2+. AB - This report introduces a novel method to load indo-1 "free acid" selectively into the cytosol of cardiac myocytes, presumably by diffusion through momentarily permeable gap junction sites during mechanical dissociation after low-Ca2+ collagenase treatment. Calibration of indo-1 fluorescence in these cells has been accomplished after subtracting average autofluorescence (AF) from time-matched non-indo-loaded cells, taking into account apparent changes in cell AF due to indo-1. There is wide variation in the degree of uncertainty of individual intracellular Ca2+ concentration ([Ca2+]i) determinations among cells, related principally to differences in cellular indo-1 content, to nonlinear aspects of the [Ca2+]-to-fluorescence ratio relationship, and to the uncertainty in the AF subtraction. Consequently, a quantitative estimate of uncertainty also may be employed in formulating weighted estimates of cytosolic [Ca2+]i. The following [Ca2+]i values in rat ventricular cells (nM; in 1 mM bathing extracellular Ca2+ concentration, 25 degrees C) are given as weighted means +/- 95% confidence intervals (unweighted values in parentheses): 138 +/- 5 (136 +/- 6, n = 44) in quiescent cells, 435 +/- 74 (482 +/- 76, n = 43) at the [Ca2+]i-transient peak during 0.5 Hz steady-state stimulation, and 760 +/- 124 (1,027 +/- 250, n = 42) at the [Ca2+]i-transient peak, postrest. Moreover, these peak [Ca2+]i values fall near the steepest portion of the force-Ca2+ curve (from intact cardiac muscle), consistent with sensitive inotropic regulation and maximal contractile reserve. PMID- 1621852 TI - In vivo 31P-NMR spectroscopy of right ventricle in pigs. AB - The energy metabolism of the right ventricle (RV) in vivo has been largely unexplored. The goal of this study was to develop and implement techniques for in vivo 31P nuclear magnetic resonance (NMR) spectroscopy of the RV free wall. A two turn, crossover-design elliptical surface coil was constructed to provide high sensitivity across the thin RV wall but minimal sensitivity in the blood-filled RV cavity. In 36 open-chest, anesthetized pigs, 31P spectroscopy of the RV free wall was performed with this coil at a field strength of 2 Tesla. Spectra were obtained from 800 acquisitions in 24 min with an average signal-to-noise ratio of 13.2 for phosphocreatine (PCr). The PCr-to-ATP (PCr/ATP) ratio of porcine RV was 1.42 +/- 0.05 (mean +/- SE), uncorrected for saturation at a repetition time of 1.8 s. With the use of literature values of the time constant of longitudinal relaxation (T1) to correct for partial saturation, the RV PCr/ATP was estimated to lie between 1.7 and 2.3. Decreased RV PCr/ATP was observed during RV ischemia and pressure overload. Thus in vivo 31P spectroscopy of the RV is readily accomplished with an appropriate surface coil and can provide new information about RV energy metabolism. PMID- 1621853 TI - Food deprivation and refeeding in the camel (Camelus dromedarius). AB - Camels thrive in arid and semiarid areas, although food and water frequently are scarce. However, the mechanisms enabling camels to withstand food deprivation are poorly understood. In this study four female camels were totally deprived of food for 4 days. Their body weight decreased by 6%. Food deprivation caused no change in total plasma protein concentration in the camel, indicating that no alterations in plasma volume occurred. When the first meal was withheld water intake was unchanged. Next day the camels showed signs of hydration with a decreased plasma Na+ concentration and an increased excretion of diluted urine. In the afternoon water intake decreased. Urine K+ excretion fell the first day and urine volume and Na+ excretion from the third day. No activation of the renin angiotensin-aldosterone system (RAAS) was observed. Plasma and urine urea concentration increased during food deprivation. Plasma glucose concentration and plasma cortisol and thyroxine levels did not change. Body temperature decreased during food deprivation. After refeeding, total plasma proteins increased temporarily by 12%, and a threefold increase in RAAS was seen, implying that both plasma volume and RAAs changed rapidly. Our results show that fluid balance was only slightly affected in the food-deprived camel. We suggest that strategies for the camel to endure food deprivation include maintenance of plasma volume and glucose concentration and a lowering of the body temperature. PMID- 1621854 TI - The 10-Hz rhythm in sympathetic nerve discharge. AB - Frequency-domain analysis was used to characterize the relationships among the rhythmic discharges recorded simultaneously from two to four sympathetic nerves in unanesthetized decerebrate cats. The major new findings were as follows. 1) The 10-Hz rhythmic discharges of different nerves cohered strongly in baroreceptor-innervated and -denervated cats. 2) The interval between the discharges of two nerves was frequency dependent in the 10-Hz band in some cats, supporting the view that the 10-Hz rhythm is generated by multiple central circuits that are coupled. 3) In some cases the central circuits responsible for the 10-Hz rhythms nonuniformly affected different nerves. 4) In baroreceptor innervated cats the coherence values for the cardiac-related discharges of any two nerves were significantly higher than those for the 10-Hz rhythms. 5) In baroreceptor-denervated cats the 10-Hz rhythmic discharges of different nerves cohered more strongly than the 2- to 6-Hz rhythms. 6) The 10-Hz rhythm usually was not a harmonic of the 2- to 6-Hz or cardiac-related rhythm. Thus these rhythms are generated independently. PMID- 1621855 TI - Effects of brain stem lesions on 10-Hz and 2- to 6-Hz rhythms in sympathetic nerve discharge. AB - We studied the effects of brain stem lesions or transection on the 10-Hz and 2- to 6-Hz rhythms in sympathetic nerve discharge (SND) in baroreceptor-denervated unanesthetized decerebrate cats. The results indicate that these two rhythms depend in part on different brain stem regions. The 10-Hz rhythm was eliminated by ablation of the rostral ventrolateral medulla (RVLM), medullary raphe complex, or pontine parabrachial and Kolliker-Fuse complex (PB/KF) or by pontomedullary border transection. Except for RVLM lesions, these procedures did not disrupt the 2- to 6-Hz rhythm in SND. In fact the power in SND at frequencies less than 6 Hz was increased by raphe or PB/KF lesions. Total power in SND was not significantly affected by raphe or PB/KF lesions, but mean arterial pressure was significantly reduced. Field potentials recorded from the RVLM (11 of 26 sites) and raphe (10 of 20 sites) were correlated to the 10-Hz rhythm in SND, further supporting a role of these areas in either generating or relaying this rhythm to sympathetic nerves. In contrast, field potentials recorded from the PB/KF were not correlated to the 10-Hz rhythm in SND. Thus this region may provide a tonic drive to the 10 Hz generator located elsewhere in the brain stem. PMID- 1621856 TI - Dietary obesity in nine inbred mouse strains. AB - The effect of 7 wk consumption of a diet containing 32.6% of kilocalories as fat [condensed milk (CM) diet] on body composition and energy intake was evaluated in nine strains of inbred mice (AKR/J, C57L/J, A/J, C3H/HeJ, DBA/2J, C57BL/6J, SJL/J, I/STN, and SWR/J). Control animals were fed a high-carbohydrate diet containing 11.6% of energy as fat (Purina Rodent Chow diet). Relative to Chow diet controls, the CM diet significantly increased carcass lipid content in six strains (AKR/J, C57L/J, A/J, C3H/HeJ, DBA/2J, and C57BL/6J), but had no or a marginal effect on adiposity in three strains of mice (SJL/J, I/STN, and SWR/J). The obesity produced by the CM diet in six strains was not due to hyperphagia. Only one of six (AKR/J) of the strains that increased adiposity on the CM diet consumed more energy than controls during the 7 wk of the experiment. The identification of inbred mouse strains that are sensitive to dietary obesity, vs. others that are resistant, provides a useful tool to pursue the metabolic and genetic basis of this trait in the mouse. PMID- 1621857 TI - Metabolism and ventilation in acute hypoxia: a comparative analysis in small mammalian species. AB - O2 consumption (VO2), CO2 production (VCO2), and minute ventilation (VE) have been measured during normoxia and hypoxia (10-20 min in 10% O2) in specimens of 27 species from 6 mammalian orders, ranging in body mass (M) from a few grams to several kilograms. In normoxia, both metabolism and VE scaled close to M3/4, VE/VO2 and VE/VCO2 therefore being independent of M. In hypoxia, VE/metabolism increased in all species (on average greater than 100%), mostly because of a drop in VO2. On average, VE was 23% above the normoxic value but in some species decreased below normoxia. VO2 dropped in all but one species, on average 35%. Body temperature decreased by variable amounts, usually more in the smallest species. The decrease in metabolism during hypoxia was positively correlated with the resting metabolic rate of the species in a manner very similar to what can be calculated from data of previously studied newborn mammals. Hence hypoxia may decrease metabolic rate by decreasing thermogenesis, with larger effects in smaller animals, whether newborns or adults, because of their higher thermogenic requirements. We conclude that 1) hypoxic hypometabolism is a general characteristic of the mammalian response to hypoxia and cannot be neglected in the interpretation of ventilatory and cardiovascular responses and 2) its magnitude is inversely related to the resting VO2 of the species and therefore could be less prominent or possibly absent in adults of larger species. PMID- 1621858 TI - Concentration thresholds for fetal swallowing and vasopressin secretion. AB - In adults, plasma osmolality thresholds for hypernatremia-induced arginine vasopressin (AVP) secretion are similar or less than thresholds for stimulation of thirst. In the fetus, the thresholds for swallowing stimulation and AVP secretion have not been defined. Fetal swallowing and AVP secretory responses to hypertonic NaCl and urea were determined in six fetuses (130 +/- 1 1 days) chronically prepared with thyrohyoid, nuchal and thoracic esophagus, and diaphragm electromyograms (EMG), an esophageal flow probe, and vascular catheters. Fetuses received intracarotid injections (0.15 ml/kg) of increasing concentrations of NaCl (0.15, 0.30, 0.45, 0.60, 0.75, and 0.90 M), administered at 2-min intervals. A swallow was defined as a coordinated time-sequence of fetal thyrohyoid, nuchal esophagus, and thoracic esophagus EMG activity. The threshold saline concentration for swallowing was defined as the minimum NaCl dose eliciting swallow responses (within 20 s) after four of five injections at each dose. During a 2-h control period swallowing averaged 25.0 +/- 10.1 ml/h and 39.4 +/- 14.6 swallows/h. The mean NaCl threshold concentration for swallowing stimulation was 0.56 +/- 0.06 M. Fetal plasma AVP (2.6 +/- 0.9 pg/ml) increased significantly at the maximum subthreshold (7.6 +/- 4.0 pg/ml) and the threshold NaCl concentration (8.2 +/- 4.0 pg/ml) that stimulated swallowing. On a subsequent day, equiosmolar urea injections increased plasma AVP (from 2.2 +/- 0.7 to 7.6 +/- 2.6 pg/ml) but had no effect on swallowing activity. Fetal mean arterial blood pressure increased after injections of threshold saline and urea concentrations. Fetal arterial blood osmolality and sodium concentration did not change during any study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621859 TI - Central nervous system catecholamine content and norepinephrine release after AV3V ablation. AB - Electrolytic ablation of the periventricular tissue surrounding the anteroventral third cerebral ventricle (AV3V-X) results in immediate increases in norepinephrine release in the paraventricular hypothalamic nucleus/anterior hypothalamus (P/A) and in the dorsomedial medulla (DM) and depletion of norepinephrine and epinephrine throughout the brain. The present study determined whether catecholamine depletion and/or altered norepinephrine release persisted after recovery from the acute effects of AV3V-X. Fourteen to eighteen days after surgery, catecholamine concentrations throughout the brain and norepinephrine release in the P/A and DM during hemorrhage were measured in control-operated and AV3V-X rats. AV3V-X decreased epinephrine content only in the midbrain, increased norepinephrine only in the cortex, and produced no differences in central nervous system dopamine. Hemorrhage-induced norepinephrine release was significantly greater in the P/A of AV3V-X rats than in control animals, whereas norepinephrine release in the DM increased equally in both groups. Thus AV3V-X does not result in chronic global central nervous system catecholamine depletion and enhances norepinephrine release in the P/A during hemorrhage. PMID- 1621860 TI - Sham feeding in intact and chronic decerebrate rats. AB - In the traditional sham-feeding paradigm, the amount of sugar solution consumed by the rat is influenced by its concentration and the open or closed condition of the gastric fistula. The present experiments examine: 1) whether sham intake effects obtained under the "intraoral intake" paradigm, developed to explore controls of ingestion in otherwise aphagic preparations such as the decerebrate, are similar to those of previous studies in which intact rats obtained the fluid stimulus by spout licking; and 2) whether chronic decerebrate and intact rats show a similar elevation of their sucrose intake when ingesting with an open (sham intake) vs. closed gastric fistula. Experiment 1 showed that sham intraoral intake exceeded intake in the closed condition only for sucrose concentrations greater than 0.1 M. After it was established that the results obtained with the intraoral paradigm were consistent with those reported in the literature, the new paradigm was applied to the chronic decerebrate rat in experiment 2 to determine whether forebrain structures are necessary for sham-feeding effects. The effect of sucrose concentration and fistula condition on the behavior of chronic decerebrates was similar to that of intact rats. Like intact rats, decerebrate rats consumed more sucrose in the open condition but only for concentrations exceeding 0.1 M. This concentration-dependent sham sucrose intake of chronic decerebrate rats provides compelling evidence that the integration of sucrose's taste and postingestive effects that modulates ingestive behavior can be accomplished by the caudal brain stem. PMID- 1621861 TI - Expiratory bulbospinal neurons of dogs. I. Control of discharge patterns by pulmonary stretch receptors. AB - To better understand expiratory bulbospinal (EBS) neuronal processing of afferent patterns from slowly adapting pulmonary stretch receptors (PSRs), the responses of these caudal medullary neurons to various inflation patterns were analyzed in thiopental sodium-anesthetized paralyzed dogs. Normocapnic ventilation was obtained from lung inflations delivered during the neural inspiratory phase of control respiratory cycles by a solenoid ventilator triggered by the onset of phrenic nerve activity. Test inflation patterns, delivered during the neural expiratory (E) phase of specific cycles, were separated by 6-10 control cycles and consisted of slow augmenting and decrementing ramps and steps. Transpulmonary pressure (Pt) was used as an index of PSR activity, and the discharge patterns of single EBS neurons were quantified using cycle-triggered histograms. Based on the time course of the discharge pattern during no-inflation cycles, two types of neurons were identified. Type D, the most common, exhibited a decrementing-like pattern, while type A exhibited an augmenting-plateau pattern. Plots of discharge frequency vs. Pt for type D neurons consisted of a linear excitatory phase (1 less than Pt less than 4.6 mmHg) and a linear inhibitory phase (4.6 less than Pt less than 12 mmHg). Type A neurons exhibited only a linear inhibitory phase for 3.3 less than Pt less than 12 mmHg. Because the responses to step inflations (4 s duration) exhibited only a small amount of time dependency, and the activation Pt of PSRs, but not of the other pulmonary receptors with vagal fibers, is in the proper range, it appears that PSRs may mediate both excitatory and inhibitory components of the neuronal response. These data suggest that discharge patterns of the caudal EBS neurons in dogs are highly dependent on the time course of Pt in a predictable manner, and implicate the importance of instantaneous lung volume in the control of the E musculature and the optimization of the breathing pattern. PMID- 1621862 TI - Expiratory bulbospinal neurons of dogs. II. Laterality of responses to spatial and temporal pulmonary vagal inputs. AB - Pulmonary mechanoreceptors with vagal fibers produce a combination of excitation and inhibition in the majority of the expiratory bulbospinal (EBS) neurons of dogs. Both aspects of this transpulmonary pressure-dependent neuronal response appear to be slowly adapting and activated at low pressure levels, suggesting the involvement of the slowly adapting pulmonary stretch receptors (PSRs). The purpose of the present study was to determine the contribution of different afferent pathways to each of the response components and to characterize the spatial and temporal processing of ipsi-, contra-, and bilateral vagal afferent inputs by two types of EBS neurons. For this purpose low-intensity electrical stimulation of the intact, desheathed, vagus nerves was used in thiopental sodium anesthetized paralyzed dogs. The phrenic neurogram was used to synchronize both ventilation and stimulation. During test respiratory cycles, pulse trains (4-5 s duration) were applied during the neural expiratory phase to each and both vagus nerves. The mean discharge frequency (Fn) during the stimulus period was obtained from cycle-triggered histogram data. Plots of Fn vs. stimulus strength and Fn vs. stimulus frequency suggest that inhibition of both type D and type A EBS neurons is mediated mainly by the ipsilateral vagus nerve, and that the excitation of type D neurons is mediated bilaterally. These conclusions are also supported by inflation responses obtained before and after unilateral vagotomies. Differences in latencies and spatial and temporal summation characteristics suggest the possible involvement of different 1) types of PSRs, 2) central pathways, and/or 3) synaptic mechanisms in the biphasic response of the caudal ventral EBS neurons to lung inflation. PMID- 1621863 TI - Estradiol phase-shifts circannual rhythms of golden-mantled ground squirrels. AB - Ovariectomized golden-mantled ground squirrels (Spermophilus lateralis) were implanted with estradiol benzoate (EB)-filled or empty capsules. Body weight was monitored for at least 1 yr before, during, and after hormone treatment. EB treatment of 6-7 mo duration, restricted to the weight-gain phase, decelerated weight gain and delayed attainment of peak weight by 34 days; the period of the circannual rhythm, measured between successive trough weights, was 36 days longer in squirrels treated with estradiol than in untreated animals. EB treatment of 2- to 4-mo duration, restricted to the weight-loss phase, accelerated weight loss, advanced attainment of trough weights by 57 days, and decreased the period of the circannual rhythm by 66 days. Estradiol-induced phase delays and advances were preserved in the year after discontinuation of hormone treatment. These results favor the existence of circannual phase-response curves to hormones and provide a system for pharmacological manipulation of circannual rhythms. PMID- 1621864 TI - Effect of sinoaortic denervation on pressor responses in pregnant rats. AB - We tested the hypothesis that augmented arterial baroreflex activity contributes to attenuation of pressor responses in intact pregnant animals by comparing changes in blood pressure and heart rate during infusions of angiotensin II, phenylephrine, and vasopressin in chronically instrumented pregnant and virgin rats approximately 5 wk after sinoaortic denervation (SAD) or sham surgery. Baseline mean arterial pressure was significantly lower in pregnant animals in both the sham-operated (pregnant 91.7 +/- 1.7 mmHg, virgin 103.7 +/- 2.5 mmHg) and SAD states (pregnant 107.3 +/- 4.0 mmHg, virgin 114.1 +/- 4.0 mmHg). Pressor responses to all three agents were significantly blunted in pregnant animals compared with similarly treated virgins, with the magnitude of attenuation similar in both sham and SAD states. Heart rate decreased similarly in reflex intact pregnant and virgin animals during pressor infusions. These findings suggest that attenuated pressor responses in the pregnant rat are due primarily to mechanisms other than augmentation of arterial baroreflex activity and are consistent with a generalized reduction in vascular sensitivity during gestation. PMID- 1621865 TI - Mifepristone (RU 486), a blocker of type II glucocorticoid and progestin receptors, reverses a dietary form of obesity. AB - The effect of mifepristone (RU 486), a blocker of type II glucocorticoid receptors on the development of obesity that follows the feeding of a high-fat (HF) diet to Osborne-Mendel (OM) rats, has been investigated. OM rats fed a HF diet gained more weight and had larger retroperitoneal and parametrial fat pads than OM rats fed a high-carbohydrate low-fat (LF) diet. RU 486 (30 mg.kg-1.day-1) for 14 days completely reversed the body weight gain and the increase in fat pad size of OM rats fed a HF diet. RU 486 had no effect on body weight of OM rats fed a LF diet, but did reduce fat pad weights. The data suggest that type II glucocorticoid receptor activity modulates body fat deposition and is essential for the development of obesity, although a minor role for progestin receptor activity cannot be ruled out. PMID- 1621866 TI - Differential inhibition of fat intake in two strains of rat by the peptide enterostatin. AB - The effect of enterostatin, the amino-terminal pentapeptide of pancreatic procolipase, on food intake was investigated in two strains of rat, the dietary fat-sensitive Osborne-Mendel (OM) rat and the dietary fat-resistant S5B/Pl rat. After an overnight fast, enterostatin inhibited intake of high-fat (HF) but not low-fat (LF) diets in OM rats, but had no effect in S5B/Pl rats. When fed a macronutrient three-choice diet, OM rats selected fat preferentially, whereas S5B/Pl rats selected carbohydrate. Enterostatin specifically inhibited the intake of fat in OM rats but not S5B/Pl rats fed a three-choice macronutrient diet. The activity of pancreatic colipase was increased in S5B/Pl rats on both HF and LF diets compared with OM rats. Pancreatic colipase activities were negatively related to the voluntary intake of fat on three-choice macronutrient diets. The data support the hypothesis that enterostatin may control the intake of dietary fat. PMID- 1621867 TI - Effects of intravenous saline infusion on fetal ovine lung liquid secretion. AB - These studies were designed to investigate the relationship between body fluid volume expansion and secretion of lung liquid in fetal sheep. Twelve fetal animals were used for saline infusion studies after providing them with indwelling vascular catheters and an exteriorized tracheal loop. An additional 10 animals were used as controls. Lung liquid production was measured using an impermeant tracer technique (Blue Dye Dextran). Saline infusion at 1.6, 4.0, 15.6, and 19.2 ml.kg-1.h-1 did not alter significantly lung liquid secretion rates. These results demonstrate that 1) intravenous infusion of saline at relatively high rates in the ovine fetus does not affect net fetal lung liquid formation rate, and 2) the lungs of chronically catheterized, unanesthetized fetal sheep probably do not participate in regulation of excess fluid and electrolytes. PMID- 1621868 TI - Models of neurohypophyseal homeostasis. AB - Rats subject to prolonged (3-6 days) hypernatremia show significantly decreased pituitary vasopressin content as well as increased levels of hypothalamic vasopressin mRNA; these values return to baseline levels after the stimulus is removed. In this paper, we tested whether a single cellular mechanism for regulation of synthesis could account for the experimental observations of both pituitary hormone depletion-repletion and hypothalamic mRNA content. We developed several "minimal" models of vasopressin synthesis in which control of hormone synthesis was regulated exclusively by transcription, translation, or mRNA decay and tested each model to see which best emulated the dynamics of neuro hypophyseal vasopressin content and hypothalamic vasopressin mRNA. Experimental data provided parameters for pituitary content, baseline and stimulated release rates, mRNA decay, transcription, and translation. Models based exclusively on translation and mRNA decay failed to produce predictions similar to experimental observations. Of the models tested, the transcription model provided predictions most consistent with laboratory data, although some quantitative differences remain. The results of the computer modeling strongly suggest that transcription represents the predominant means by which magnocellular neurons regulate vasopressin synthesis. PMID- 1621869 TI - Verapamil prevents insulin antinatriuresis in euglycemic rats. AB - To determine whether calcium entry is necessary for insulin antinatriuresis, urinary sodium excretion was determined before and during euglycemic insulin administration in rats receiving verapamil (10 micrograms.kg-1.min-1) or vehicle. In vehicle rats, insulin reduced sodium excretion from 2.7 +/- 0.5 to 0.98 +/- 0.2 mu eq/min (P less than 0.05) without altering arterial pressure or inulin clearance. Insulin did not reduce sodium excretion in rats receiving verapamil. Baseline mean arterial pressure was lower in verapamil rats than in vehicle rats. To exclude the possibility that lower baseline arterial pressures prevented insulin antinatriuresis, insulin's effect on sodium excretion was determined in rats receiving captopril at a dose that reduced arterial pressure to the level observed in verapamil rats, and in verapamil rats with angiotensin II levels fixed to maintain arterial pressure equivalent to vehicle rats. In captopril rats, insulin reduced (P less than 0.05) sodium excretion from 1.07 +/- 0.3 to 0.3 +/- 0.01 mu eq/min, even though arterial pressure was not different from that in verapamil rats. Insulin failed to reduce sodium excretion in verapamil rats receiving angiotensin II. Thus verapamil prevents insulin antinatriuresis by renal mechanisms related to inhibition of calcium entry. Additionally, insulin antinatriuresis is independent of angiotensin II. PMID- 1621870 TI - Two families of phase-response curves characterize the resetting of the hamster circadian clock. AB - Phase-response curves (PRCs) have been reported for a wide variety of agents that induce phase shifts in the circadian rhythm of locomotor activity in the golden hamster. Many of these PRCs appear to be quite similar to one another. Because of the important role that the interpretation of PRCs has played in understanding the dynamics of the mammalian circadian pacemaker, a review of PRCs for the golden hamster reported from 1964 to 1991 was conducted to systematically summarize the common characteristics among these PRCs. Plots of phases associated with the peak of the advance portions, or of phases associated with the transitions between the delay and advance portion of the PRCs, revealed bimodal distributions of PRCs 11-13 h apart. Mardia-Watson-Wheeler circular test statistics indicated that the PRCs were distributed as two distinct populations. PRCs were either characteristic of those for light pulses (L-PRCs), or of those for dark pulses (D-PRCs). Taken with anatomical and physiological evidence, these data suggest that either one or two final common pathways may exist to mediate the phase-shifting effects of different stimuli. PMID- 1621871 TI - CCK-A receptors mediate the effect of cholecystokinin on vasopressin but not on cortisol in pigs. AB - Bolus intravenous injections of cholecystokinin (CCK) octapeptide induce a rapid rise in plasma vasopressin and a later increase in cortisol in the prepubertal pig. To determine whether these endocrine responses involve CCK-A or CCK-B receptors, this experiment investigated the effect of CCK (1 microgram/kg) in pigs (n = 7) pretreated with the CCK-A antagonist L 364718 (70 microgram/kg) or the CCK-B antagonist L 365260 (10 ng/kg and 10 micrograms/kg). The animals were prepared with jugular vein catheters and given the antagonist vehicle, L 364718, or L 365260 10 min before administration of CCK or saline. Analysis of hormone concentrations in blood samples taken 2, 5, 10, and 20 min after the second injection indicated that an abrupt rise in vasopressin, detectable within 2 min of CCK administration, occurred after vehicle or L 365260 pretreatment but not when CCK was preceded by L 364718. In contrast, the rise in plasma cortisol that was observed approximately 15 min after CCK injection was not prevented by either antagonist. Thus peripherally administered CCK induces vasopressin release by CCK A receptor activation, in agreement with its inhibitory effect on food intake in this species. However, the effect of CCK on cortisol secretion does not appear to involve either CCK-A or CCK-B receptors. PMID- 1621872 TI - Short-term effect of aldosterone on Na-Cl transport across equine colon. AB - In ponies fed concentrated (pelleted) meals, postprandial increases of plasma aldosterone have been temporally associated with a decrease in colonic fluid volume that parallels the conclusion of postfeeding fermentation. To determine the significance of short-term increases of plasma aldosterone on the rate of colonic Na absorption, in vitro transport studies were conducted on the mucosae of three morphologically distinct colonic segments (i.e., ventral, dorsal, and small colons) from ponies infused with a high physiological concentration of aldosterone for an 8-h period. In control ponies, basal NaCl absorption across the proximal colon (ventral and dorsal colons) was amiloride-insensitive and electroneutral. In aldosterone-treated ponies, the rate of electroneutral Na absorption was doubled in both segments and a small, amiloride-sensitive current was detected in the dorsal colon. However, consistent with previous observations [Clarke and Argenzio. Am. J. Physiol. 259 (Gastrointest. Liver Physiol. 22): G62 G69, 1990], expression of electroneutral Na absorption in the ventral colon required pretreatment of the tissues with an inhibitor of prostaglandin synthesis, i.e., indomethacin. In the distal (small) colon, basal absorption was entirely electrogenic and amiloride-sensitive, and aldosterone treatment tripled the rate of absorption. The above findings are consistent with the notion that postprandial hyperaldosteronism can significantly increase colonic Na absorption and, thereby, may facilitate colonic fluid absorption during the concluding period of meal-induced fermentation (8-12 h postfeeding). However, in the ventral colon (i.e., the principal site of fermentation), mineralocorticoid action does not dominate control of electroneutral Na transport because accelerated absorption could be abolished by the antiabsorptive effect of local prostanoids. PMID- 1621873 TI - Absence of focal glomerulosclerosis in aging analbuminemic rats. AB - The Nagase analbuminemic rat (NAR), a mutant of the Sprague-Dawley (SD) strain, exhibits high levels of plasma cholesterol (Chol), thrombocytosis, and enhanced platelet aggregability, which might promote glomerulosclerosis (GS). To determine whether NAR are more susceptible than SD rats to aging GS, young (3-mo-old) and aging (18-mo-old) SD rats and NAR were studied. In young NAR, glomerular pressure and glomerular volume were lower, whereas total and high-density lipoprotein plasma Chol levels were higher than in young SD rats. Aging SD rats developed glomerular hypertension and hypertrophy. Less glomerular enlargement and subnormal glomerular pressures were seen in aging NAR. Enhanced platelet aggregation developed in aging SD rats, approaching the values seen in NAR. Similarly elevated levels of low-density lipoprotein Chol were seen in additional SD rats and NAR studied at 12 mo of age. Plasma triglyceride (TG) levels were lower in NAR at this age. Only SD rats developed proteinuria and exhibited GS and glomerular lipid deposits at 18 mo of age. Reduced glomerular wall stress due to lower glomerular pressure and volume as well as lower TG levels may explain the absence of GS in aging NAR despite plasma lipid and platelet abnormalities. PMID- 1621874 TI - Geometry of blood-tissue exchange in bat flight muscle compared with bat hindlimb and rat soleus muscle. AB - We investigated the relationship between capillary-to-fiber geometry and muscle aerobic capacity by comparing the bat flight muscle (pectoralis muscle), i.e., an ultimate case of extreme O2 demand in a mammalian skeletal muscle, with bat hindlimb and rat soleus muscles. At a given sarcomere length (2.1 microns), fiber cross-sectional area was considerably smaller in bat muscles (pectoralis 318 +/- 10 microns 2, hindlimb 447 +/- 35 microns 2) than in rat soleus muscle (2,027 +/- 125 microns 2). Capillary number per fiber cross-sectional area was much greater in bat pectoralis (6,394 +/- 380/mm2) than in bat hindlimb and rat soleus muscle (2,865 +/- 238 and 1,301 +/- 129/mm2, respectively; all values normalized to 2.1 microns sarcomere length). At the same sarcomere length (2.1 microns), the degree of tortuosity and branching of capillaries were significantly greater in bat pectoralis than in bat hindlimb and rat soleus muscle. In bat flight muscle, capillary length per fiber volume was very high (9,025 +/- 342/mm2). It was 2.2- and 5.4-fold larger than in bat hindlimb and rat soleus, respectively. Mitochondria occupied 35.3 +/- 1.2, 16.5 +/- 1.3, and 6.1 +/- 0.9% of the muscle fiber volume in bat pectoralis, hindlimb, and rat soleus muscles, respectively. There was a strong correlation between capillary length (as well as capillary surface) per fiber volume and mitochondrial volume density in all muscles. Considering capillary supply and mitochondrial volume on an individual fiber basis, we found that 1) the number of capillaries around a fiber was linearly related to mitochondrial volume per micron length of fiber in the muscles but that 2) capillary surface per fiber surface, at given mitochondrial volume per micron length of fiber, was about twice as large in bat pectoralis as in rat soleus muscle, whereas in bat hindlimb it was intermediate between that in bat pectoralis and that in rat soleus muscle. This was due to the differences in fiber size (rat soleus greater than bat muscles) and capillary-to-fiber ratio (bat pectoralis greater than hindlimb) between the muscles. It is notable that in the bat, the substantially greater O2 transfer capacity of the flight muscle compared with hindlimb was achieved by increasing the size of the capillary-to fiber interface, i.e., capillary-to-fiber surface, via an increase in capillary number rather than by substantially reducing fiber size. PMID- 1621875 TI - Human placental vitamin B6 (pyridoxal) transport: normal characteristics and effects of ethanol. AB - The aims of this study were to define normal human placental transport of pyridoxal, an important form of vitamin B6 in pregnancy, and to determine the effect of short-term alcohol on this process. Our studies used the isolated single cotyledon from the term placenta. Pyridoxal crossed the human placenta readily in both directions, but the transfer was a little less than half that of antipyrine and was significantly greater in the direction of the fetus. Pyridoxine appeared to have a similar clearance from the maternal compartment as pyridoxal, but transport of intact pyridoxal 5'-phosphate was much smaller. There was no saturable transfer of pyridoxal, and it was not transferred from the maternal to fetal compartments against a concentration gradient. Placental concentration of pyridoxal exceeded both maternal and fetal perfusate pyridoxal concentrations, but this concentration was equal for both perfusion directions. These composite data are most suggestive of passive transport of pyridoxal across the placenta, binding of the vitamin in the placenta as an explanation for its concentration there, and greater phosphorylation of pyridoxal in the placenta when the compound is transferred in the fetal direction, possibly displacing pyridoxal from its binding sites and permitting its greater release into the fetal compartment. Alcohol, 400-250 mg/dl over 2.5 h, inhibited the transport of pyridoxal from the maternal to fetal compartments by approximately 42% (P = 0.03) and resulted in a lower transfer of pyridoxal 5'-phosphate into the fetal perfusate (P = 0.02). PMID- 1621876 TI - Individual, but not simultaneous, glucagon and cholecystokinin infusions inhibit feeding in men. AB - Pancreatic glucagon and cholecystokinin octapeptide (CCK-8) were intravenously infused (1 ml/min for 10 min) alone or in combination beginning 15 min after normal-weight men had eaten a 500-ml tomato soup preload and 5 min before they were served a lunch of macaroni and beef with tomato sauce. Infusion of approximately 3 ng.kg-1.min-1 glucagon or approximately 2 ng.kg-1.min-1 CCK-8 each reduced test meal size. However, simultaneous infusion of these peptide doses reduced meal size less than the sum of the peptides' individual effects. Infusions of approximately 1.5 ng.kg-1.min-1 glucagon or approximately 1 ng.kg 1.min-1 CCK-8 had neither individual nor interactive effects on meal size. Psychophysical ratings failed to detect nonspecific side effects after any of the infusions. That exogenous glucagon and CCK-8 each reduced meal size without side effects suggests that these peptides may participate in the physiological control of human appetite; that their simultaneous infusion resulted in an infra-additive reduction in meal size suggests that they can interact antagonistically. PMID- 1621877 TI - Exercise-induced sympathetic FFA mobilization in VMH-lesioned rats is normalized by fasting. AB - This study investigates whether reduced sympathetic responses during physical exercise in ventromedial hypothalamus (VMH)-lesioned obese rats are the direct result of damage to hypothalamic circuits or a secondary effect of the altered metabolism in obesity. Obese, VMH-lesioned rats and lean controls were deprived of food for 48 h and submitted to 15 min of swimming. Food-deprived lean and obese rats displayed increased free fatty acid mobilization and utilization, whereas blood glucose concentrations were decreased. Basal plasma insulin levels were reduced by fasting in both groups, when compared with the ad libitum situation, but remained higher in the obese animals. Fasting augmented the norepinephrine response of the obese rats, resulting in equal profiles in lean and obese animals. These results indicate that VMH-lesioned animals are able to increase the sympathetic activation of adipose tissue during exercise to overcome an energy deficiency. Therefore, the function of the VMH in the regulation of the sympathetic nervous system controlling metabolism can be taken over by redundant mechanisms. The reduced sympathetic activity in ad libitum fed VMH-lesioned animals is therefore likely to be the result of the altered metabolism. PMID- 1621878 TI - Mechanism of intracardiac shunting in the turtle Pseudemys scripta. AB - Two principal hypotheses account for right-left (R-L) intracardiac shunting in reptiles. The "pressure shunting" hypothesis proposes no functional separation between the ventricular cava during systole. The "washout shunting" hypothesis suggests that during systole, the cavum pulmonale (CP) is functionally separate from the rest of the ventricle. The purpose of this study was to test these hypotheses during control, after acetylcholine (ACh) administration, after epinephrine (Epi) administration, and during apnea. Anesthetized (pentobarbital) turtles (Pseudemys scripta) were mechanically ventilated and three nonocclusive catheters were implanted into the right atrium (RAt), left atrium (LAt), and CP. In addition, three blood gas catheters connected to a mass spectrometer were implanted into the RAt, LAt, and right or left aortic arch for measurement of PO2. A tracer gas, He dissolved in saline, was sequentially injected into the three cardiac chambers and was detected by the mass spectrometer. The presence of R-L shunting was assessed with the blood PO2 and PHe measurements. ACh produced R L shunting in all animals. No R-L shunting occurred after Epi administration and 20 min of apnea. In all animals after ACh administration, He was detected in an aorta after He infusion in the RAt and LAt, but never after infusion of He into the CP. These results from this preparation are inconsistent with the pressure hypothesis and support the washout hypothesis of intracardiac shunting. PMID- 1621879 TI - Automaticity and the ACT* theory. AB - An explanation of automaticity within the framework of the Adaptive Control of Thought (ACT*) production system theory (Anderson, 1983, 1987) is presented. There is no automaticity mechanism per se in ACT*. This is as we would expect it to be. It would be the exception rather than the rule that we would find in a scientific theory mechanisms that directly correspond to natural language concepts. The critical question is whether ACT* can give an account of the phenomena associated with the term automaticity. This article is structured as follows: First, I will try to identify the phenomena of automaticity to be explained, then give a brief overview of the ACT* theory, and finally explain how these phenomena of automaticity are to be understood in terms of the theory. PMID- 1621880 TI - The ecology of automaticity: toward establishing the conditions needed to produce automatic processing effects. AB - In the past 15 years, the single term automatic has been applied to a diversity of laboratory phenomena that differ as to the preconditions necessary for their occurrence. Several major strains of automaticity are distinguished, based on the experimental conditions under which they are obtained: preconscious automatic processes, requiring only the proximal stimulus event; postconscious automatic processes, similar to preconscious effects but needing a recent activation or "priming" event for their operation; and goal-dependent automatic processes, which occur only when a specific, intentional processing goal is in place. It is argued that to more accurately specify the conditions under which an automatic effect will occur in the natural environment, greater attention needs to be given to aspects of the experimental paradigm (e.g., subjects' task goal, questionnaire administrations, previous tasks) that might be necessary to produce the effect. PMID- 1621881 TI - Automaticity and cognitive anatomy: is word recognition "automatic"? AB - Recent progress in neural imaging technologies such as positron emission tomography and dense-array recording of event-related potentials has greatly increased the capacity for in vivo measurement of cognitively relevant processing activity within the human brain. Data from these neural imaging technologies can be combined with behavioral data from standard chronometric techniques to enhance computational modeling of human cognition. Applications of neural data to issues of attention and automaticity are illustrated in the domain of visual word recognition, addressing the question "Is word recognition automatic?" PMID- 1621882 TI - A parallel distributed processing approach to automaticity. AB - We consider how a particular set of information processing principles, developed within the parallel distributed processing (PDP) framework, can address issues concerning automaticity. These principles include graded, activation-based processing that is subject to attentional modulation; incremental, connection based learning; and interactivity and competition in processing. We show how simulation models, based on these principles, can account for the major phenomena associated with automaticity, as well as many of those that have been troublesome for more traditional theories. In particular, we show how the PDP framework provides an alternative to the usual dichotomy between automatic and controlled processing and can explain the relative nature of automaticity as well as the fact that seemingly automatic processes can be influenced by attention. We also discuss how this framework can provide insight into the role that bidirectional influences play in processing: that is, how attention can influence processing at the same time that processing influences attention. Simulation models of the Stroop color-word task and the Eriksen response-competition task are described that help illustrate the application of the principles to performance in specific behavioral tasks. PMID- 1621883 TI - Automatization and training in visual search. AB - In several search tasks, the amount of practice on particular combinations of targets and distractors was equated in varied-mapping (VM) and consistent-mapping (CM) conditions. The results indicate the importance of distinguishing between memory and visual search tasks, and implicate a number of factors that play important roles in visual search and its learning. Visual search was studied in Experiment 1. VM and CM performance were almost equal, and slope reductions occurred during practice for both, suggesting the learning of efficient attentive search based on features, and no important role for automatic attention attraction. However, positive transfer effects occurred when previous CM targets were re-paired with previous CM distractors, even though these targets and distractors had not been trained together. Also, the introduction of a demanding simultaneous task produced advantages of CM over VM. These latter two results demonstrated the operation of automatic attention attraction. Visual search was further studied in Experiment 2, using novel characters for which feature overlap and similarity were controlled. The design and many of the findings paralleled Experiment 1. In addition, enormous search improvement was seen over 35 sessions of training, suggesting the operation of perceptual unitization for the novel characters. Experiment 3 showed a large, persistent advantage for CM over VM performance in memory search, even when practice on particular combinations of targets and distractors was equated in the two training conditions. A multifactor theory of automatization and attention is put forth to account for these findings and others in the literature. PMID- 1621884 TI - Attention and preattention in theories of automaticity. AB - The theoretical relation between preattentive processes and automatic processes is different in different approaches to attention and automaticity. In the modal view, automatic and preattentive processes are one and the same; automatic processing is preattentive. In recent views that treat automaticity as a memory phenomenon, automatic processing is postattentive. These views are described and evidence for them is discussed. Two experiments are reported that test whether the training that makes processing automatic also makes it preattentive. The data suggest a dissociation between automatic and preattentive processes that is more consistent with the memory view of automaticity than with the modal view. PMID- 1621885 TI - Automaticity and preattentive processing. AB - The characteristics of automatized performance resemble those of preattentive processing in some respects. In the context of visual search tasks, these include spatially parallel processing, involuntary calling of attention, learning without awareness, and time-sharing with other tasks. However, this article reports some evidence suggesting that extended practice produces its effects through different mechanisms from those that underlie preattentive processing. The dramatic changes in search rate seem to depend not on the formation of new preattentive detectors for the task-relevant stimuli, nor on learned abstracted procedures for responding quickly and efficiently, but rather on changes that are very specific both to the particular stimuli and to the particular task used in practice. We suggest that the improved performance may depend on the accumulation of separate memory traces for each individual experience of a display (see Logan, 1988), and we show that the traces differ for conjunction search in which stimuli must be individuated and for feature search where a global response to the display is sufficient. PMID- 1621886 TI - Introduction of the Soper Lecture. PMID- 1621887 TI - Results of a community-based Aedes aegypti control program in Merida, Yucatan, Mexico. AB - This report describes the results of a community-based Aedes aegypti control program in Merida, Yucatan, Mexico. Baseline surveys concerning knowledge, beliefs, and practices of 577 women and a larval survey of 616 house lots were carried out in October 1989. Following development of a public health communication intervention from this data, the program was implemented in six communities. Evaluation used an untreated control group design with pretest and two post-tests, one at completion and one six months later. Significant changes in knowledge and behavior were seen in the treatment group in both post-tests. Women in the intervention group were able to identify the Ae. aegypti mosquito, the larval production sites of the mosquito, and appropriate control methods. A behavior change proxy was measured by examining changes in the Breteau (number of positive containers/100 houses surveyed) and container indices. The Breteau index remained the same in the intervention group while it increased significantly in the comparison group. Changes were also seen with respect to individual containers. This project demonstrated that a community-based communication program aimed at larval production site elimination or control can be effective in changing behavior and reducing larval production sites. PMID- 1621888 TI - Malaria chemoprophylaxis using proguanil/dapsone combinations on the Thai Cambodian border. AB - The Thai-Cambodian border is a difficult area in which to provide adequate malaria chemoprophylaxis because of multiple drug-resistant Plasmodium falciparum. In 1990-1991, Thai soldiers were randomly selected to receive proguanil (200 mg/day) combined with dapsone (4 mg or 12.5 mg/day) (n = 184) or pyrimethamine/dapsone (12.5 mg and 100 mg/week) (n = 177). Doxycycline (100 mg/day) was given to men with glucose-6-phosphate dehydrogenase deficiency (n = 77). Falciparum malaria attack rates were the same whether proguanil/dapsone (10.3%) or pyrimethamine/dapsone (11.3%) was used. However, proguanil/dapsone was more effective than pyrimethamine/dapsone in preventing vivax malaria (1.6% versus 12.4%). Men receiving doxycycline had falciparum malaria (3.9%) and vivax malaria (1.3%) at low rates. Adjusting the dapsone component from 4 mg to 12.5 mg did not improve the prophylactic effectiveness. Hematologic toxicity was not observed with the proguanil/dapsone combination. We conclude that proguanil/dapsone is not a useful alternative for malaria chemoprophylaxis on the Thai-Cambodian border. PMID- 1621889 TI - First reported outbreak of classical dengue fever at 1,700 meters above sea level in Guerrero State, Mexico, June 1988. AB - An outbreak of classical dengue fever occurred from March to August 1988 in the city of Taxco, Guerrero State, Mexico. Taxco is at an elevation of 1,700 meters above sea level, and this study represents the highest altitude at which an outbreak of dengue has been documented. An investigation was conducted to obtain serologic confirmation of dengue infection, determine the extent of the outbreak, and identify risk factors for dengue illness. Toxorhynchites cell lines were used for viral isolation, and hemagglutination inhibition was used to measure anti dengue antibody titers. The case definition used in the investigation was any person with fever, headache, myalgias, and arthralgias, or rash or retroocular pain. Dengue virus type 1 was isolated from five acute cases. Of 1,686 persons living in the affected area, 42% (715) met the case definition. Large (200-liter) water containers were significantly associated with infection (relative risk = 1.7, 95% confidence interval 1.5-1.9). The effect of altitude on epidemic transmission is most likely modulated by seasonal temperatures. The epidemiologic and serologic confirmation of a dengue outbreak at 1,700 meters above sea level represents the capability of Aedes aegypti to adapt to new environments, and the potential for epidemic spread in cities at comparable altitudes or higher. PMID- 1621890 TI - Outbreak of fatal illness among captive macaques in the Philippines caused by an Ebola-related filovirus. AB - Following the detection of an Ebola-like virus in cynomolgus macaques recently imported into the United States from The Philippines, studies were initiated to document transmission at export facilities located in the latter country. At one export facility, 52.8% of 161 monkeys that died over a 2.5-month period were shown to be infected with this virus using an enzyme-linked immunosorbent assay to detect antigen in liver homogenates. A case fatality rate of 82.4% was documented for the infected monkeys. The initial anti-viral antibody prevalence among the captive macaques at this facility was 25.9% (indirect fluorescent antibody titer greater than or equal to 1:16). Followup documented infection of 24.4% of initially seronegative animals and 8.7% of initially seropositive monkeys. Being held in a gang cage versus a single cage was found to be a significant risk factor for subsequent virus infection, and the presence of IFA antibody was shown to predict protection. This study documents unequivocally for the first time the presence of an Ebola-related filovirus in Asia. PMID- 1621891 TI - Population dynamics of Loa loa and Mansonella perstans infections in individuals living in an endemic area of the Congo. AB - A follow-up of Loa loa and Mansonella perstans microfilaremia was carried out in an adult population living in a highly endemic area of the Congo. Infection rates and parasite loads were found to be stable in the general population, both in the short-term (two months) and long-term (3-4 years) followup. The microfilarial status of most of the subjects examined did not change between tests. At the individual level, the microfilarial densities of L. loa and M. perstans also remained remarkably constant over time. This results in a qualitative and quantitative stability of the parasitic material available for the vectors. PMID- 1621893 TI - Mortality trends of American missionaries in Africa, 1945-1985. AB - Mortality trends of missionary staff serving in sub-Saharan Africa were tracked for the period 1945-1985. For 1945-1970, when more complete incidence data were available, the missionary death rate was approximately 40% lower, after adjustment, than would be expected in a comparable US population. This trend persisted through 1985. Between 1945 and 1970, the largest number of fatalities was attributable to malignancy, atherosclerosis, accidents, and infectious disease, and the greatest mortality risks, compared with the US experience, were from homicides, the complications of pregnancy, and infections, notably malaria, hepatitis, and polio. Beginning in the late 1950s, motor vehicle accidents became the leading cause of death. Since the 1960s, accidental causes of death have been approximately 50% higher than in the US, and homicides have been four times higher. During this same period, the infectious disease death rate decreased to approximately that within the US. Currently, the leading causes of mortality are motor vehicle accidents, malignancy, and atherosclerosis, followed by other accidental causes, notably aircraft mishaps and drownings. Viral hepatitis is presently the leading infectious disease cause of death. Other contemporary lethal infections include malaria, rabies, typhoid, Lassa fever, and retroviral infection. It was concluded that missionaries in sub-Saharan Africa had a death rate approximately half that expected in a comparable domestic control population. Preventive strategies, particularly relative to accident and infectious disease prevention, could effectively reduce mortality risk further. PMID- 1621892 TI - Prevalence and risk factors for Taenia solium taeniasis and cysticercosis in humans and pigs in a village in Morelos, Mexico. AB - In a Mexican village in which Taenia solium infection was known to be endemic, we selected a cluster sample of 368 households (21% of the total) for demographic, environmental, and diagnostic surveys, and medical histories for taeniasis and cysticercosis. Coproparasitologic studies of 1,531 participants revealed infection by Taenia sp. in four (0.3%) individuals; however, 5.8% of the respondents reported a history of having passed tapeworm proglottids in feces. Of 1,552 human serum specimens, 10.8% tested positive in the cysticercosis immunoblot assay. Seropositivity increased with age and reached a maximum in subjects ages 46-55 years. Risk factors associated with seropositivity included a history of passing tapeworm proglottids, frequent consumption of pork, and poor personal and household hygiene (P less than 0.05). A history of seizures was also significantly associated with seropositivity (P less than 0.05); approximately one-third of persons with such histories were seropositive. Of 571 pigs examined by tongue inspection, 23 (4.0%) had cysticerci; infection rates increased with the age of pigs, and were higher in pigs that habitually ran loose or were fed human feces (P less than 0.05). Goodness of fit analysis confirmed that seropositive persons (but not infected pigs) were significantly clustered within households, particularly, in households in which a member reported a history of having passed tapeworm proglottids. The results of this study have identified community behavioral and environmental practices that must be modified to prevent continued transmission of cysticercosis and taeniasis. PMID- 1621894 TI - Immunogenicity and efficacy trials in Aotus nancymai monkeys with model compounds representing parts of a 75-kD merozoite surface antigen of Plasmodium falciparum. AB - We tested the ability of a recombinant DNA-encoded fragment (C7Ag) of a Plasmodium falciparum merozoite protein (p75) and of two carrier-free peptide models (28-mer and 76-mer) to stimulate boostable antibody responses in Aotus nancymai monkeys. In addition, we evaluated protection against challenge with the Uganda Palo Alto (FUP) strain of this parasite. The data indicate that C7Ag elicited a strong and boostable IgG antibody response in all the monkeys immunized. However, studies with the peptide models demonstrated that various animals produce antibodies to different portions of this structure. When the post boost sera from monkeys immunized with C7Ag were analyzed for reactivity against two major portions of C7Ag, most of the antibody response was observed against the disulfide-bonded 76-residue region that forms a conformational immunogenic epitope. In the same sera, antibody levels against the charged helical region modeled with a 28-mer were generally low. Immunization with synthetic peptides revealed that the 76-mer stimulated an antibody response almost as strong as C7Ag, with substantial cross-reactivity against the parasite antigen. The 28-mer evoked a response that was not efficient or uniform, and showed little reactivity with the authentic parasite antigen. Aotus nancymai was shown to be susceptible to infection with the Uganda Palo Alto strain of P. falciparum; however, maximum parasitemia varied markedly in both immunized and control monkeys. Statistical analysis failed to recognize differences in maximum parasitemia between the vaccine and control groups. The variation in maximum parasitemia suggests that the FUP strain in this species of Aotus is a poor model for the detection of differences in efficacy based on maximum parasitemia. This initial study with structures based on parts of the 75-kD merozoite surface antigen of P. falciparum indicated that both the recombinant-produced protein C7 and the 76-mer synthetic peptide, when combined with a Syntex adjuvant formulation, were safe and immunogenic in A. nancymai monkeys. However, the data emphasize the problems of using animal models to evaluate the potential effects of immunogens in humans. PMID- 1621895 TI - Prevalence of antibody to the variant repeat of the circumsporozoite protein of Plasmodium vivax in Peru. AB - Individuals living in a malaria-endemic area in northern Peru were found to have antibodies to the variant repeat sequence of the circumsporozoite (CS) protein of Plasmodium vivax. The presence of IgG antibody to the predominant repeat sequence GDRAA/DGPA represented by the recombinant protein NS1(81) V20 (V20), and the variant repeat sequence ANGAGNQPG contained in the synthetic peptide Pvk247, was determined by enzyme-linked immunosorbent assay. IgG antibodies to the repeats were present in 78 (26%) of 298 serum samples; 56% of the positive serum samples had antibodies to V20 and 60% had antibodies to Pvk247. These findings stress the importance of considering the variant epitope in designing a vaccine based on the repeat region of the vivax CS protein. In a malaria-endemic area such as the one in this study, in which exposure to the variant repeat epitope may be as frequent as exposure to the predominant repeat, a vaccine based solely on the predominant repeat epitope may be ineffective against the variant form. PMID- 1621896 TI - Low frequency of anti-Plasmodium falciparum circumsporozoite repeat antibodies and rate of high malaria transmission in endemic areas of Rondonia State in northwestern Brazil. AB - In areas studied in the Rondonia State of Brazil, a high rate of malaria transmission and a low prevalence of anti-(NANP)4 antibodies are reported. The entomologic data are comparable to those observed in some malaria-endemic areas of Africa and Asia. However, the frequency of individuals with antibodies to the immunodominant epitope of the circumsporozoite protein of Plasmodium falciparum recorded in the four localities of Rondonia state was very low when compared with the frequencies recorded in other African and Asian endemic areas. Most of the studies performed in Africa and Asia concerned the native population of hyperendemic areas, whereas we studied a migrant population who were mostly from malaria-free areas of Brazil and living in Rondonia State for 2-4 years. In positive individuals the antibody production was influenced by previous malaria experience, suggesting that infective bites must occur in cumulative numbers before anti-(NANP)4 antibodies are detected. Therefore, it is possible that the individuals described in this report have not been exposed long enough to malaria infection to develop detectable levels of anti-(NANP)4 antibodies. PMID- 1621897 TI - Ultrasonography as a diagnostic aid for a district hospital in the tropics. AB - To improve diagnostic capabilities, an ultrasound unit was installed at a major hospital in Wad Medani, Sudan. During the implementation period (October 1986 to March 1987) of ultrasound service, 863 patients were examined cooperatively by Sudanese and German physicians. The service covered internal medicine (47.5%), obstetrics and gynecology (31.6%), surgery (12.5%), and pediatrics (8.4%). Pathologic findings were seen in 75% of the patients. In obstetrics, the rate of pathologic findings was 40%. Five hundred eighty-three pathologic findings were detected in organ systems that constituted the primary indication for ultrasonography (of a total of 1,009 indications). The clinical benefit of ultrasonography was evaluated in 289 randomly selected patients in a standardized questionnaire completed by the attending physicians. The final clinical diagnosis was established or substantially revised in 21.5% of the patients, based on the ultrasonographic report. The previously reported diagnosis was supported in 69.5% of the patients. Medical management was directly influenced in 26% of the patients. We conclude that the clinical benefit of ultrasonography at a district hospital in the tropics is substantial, providing cost-effective, immediate therapeutic benefits in 25% of the patients examined. The technique thereby contributes to better and more rational patient management in institutions with limited resources. PMID- 1621898 TI - Evaluation of eosinophiluria in the diagnosis of schistosomiasis hematobium: a field-based study. AB - Using Hansel's stain, eosinophiluria greater than 5% of total urinary white blood cells was found in 59% of a randomly selected population sample in an area endemic for schistosomiasis hematobium. The prevalence and mean level of eosinophiluria were significantly higher in infected subjects than in noninfected subjects (P less than 0.05). The sensitivity (80%), specificity (86%), and positive predictive value (82%) of eosinophiluria as a diagnostic index for schistosomiasis hematobium were significantly higher (Youdin index 0.66; P less than 0.05) than those of proteinuria, hematuria, and leukocyturia taken singly or in combination. However, unlike the latter three measurements, this method involves microscopy. There is a great need for a chemical method for measuring eosinophiluria. PMID- 1621899 TI - Circulating schistosomal antigen in diagnosis and assessment of cure in individuals infected with Schistosoma mansoni. AB - The effectiveness of praziquantel in treating schistosomiasis is most commonly assessed by quantitating egg production or anti-schistosome antibodies in serum. We have used a monoclonal antibody (MAb)-based antigen-capture enzyme-linked immunosorbent assay (ELISA) for the serologic diagnosis of schistosomiasis, and to monitor the efficacy of praziquantel therapy in 49 individuals with parasitologically proven schistosomiasis. The MAb used, 128C3/3/21, recognizes a repeating carbohydrate epitope expressed at all stages of parasite development, and antibodies recognizing this epitope are found in the serum of infected humans. The overall sensitivity of the ELISA was 78%, with a sensitivity of 100% for patients excreting greater than 100 eggs/g of feces and 72% for those excreting less than 100 eggs/g of feces. The positivity of the ELISA was directly related to the fecal egg counts obtained on days -3, -2, and -1 before treatment with praziquantel, but there was no correlation between antigen levels and the clinical stage of the disease. After praziquantel treatment, we observed a highly significant correlation (P less than 0.0001) between the time elapsed since treatment and the decrease in antigenemia. Furthermore, although no eggs were detected in any of the stool specimens at week 12 after treatment, the antigen was detected in 21% of the treated patients (seven of 33 ELISA-positive patients). Antigen levels decreased over the 12-week period in six of these patients, whereas the antigen level increased with time in one individual. The persistence of antigenemia suggests that these individuals are either still clearing antigen or remain infected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621900 TI - Renal abnormalities in microfilaremic patients with Bancroftian filariasis. AB - To determine the frequency of renal abnormalities occurring with Bancroftian filarial infections and to assess the effects of treatment on such abnormalities, we initiated a prospective, hospital-based study of 20 microfilaremic and five amicrofilaremic patients with Wuchereria bancrofti infections. Thorough clinical evaluations and detailed renal assessments were made prior to treatment and at multiple time points for 60 days following a standard twelve-day course of treatment with diethylcarbamazine (DEC). There were two important findings. First, even prior to DEC treatment, almost half of the microfilaremic patients had hematuria and/or proteinuria. Second, treatment with DEC induced these same abnormalities in almost all of the remaining microfilaremic patients. However, this DEC-induced hematuria and/or proteinuria was transient, and the long-term response to DEC in all of the microfilaremic patients was resolution of the abnormal renal findings during the two-month followup period. In the amicrofilaremic study patients, no hematuria or proteinuria was detected before, during, or after treatment with DEC. PMID- 1621901 TI - Amebiasis complicating carcinomas: a diagnostic dilemma. AB - Two black African women and one black American man had carcinomas of cervix, perineum, and sigmoid colon, respectively. In each of these patients, trophozoites of Entamoeba histolytica had invaded the surface of the tumor, and in some areas had invaded more deeply into the stroma between the tumor cells. Although it is well known that cutaneous amebiasis of anus, penis, vulva, and cervix can mimic squamous cell carcinoma, it may be, perhaps, less well known that carcinomas at these sites may be colonized by trophozoites of E. histolytica. In patients with amebiasis but without an associated carcinoma, a correct diagnosis of amebiasis spares the patient unnecessary and sometimes mutilating surgery. But a diagnosis of amebiasis, when there is an unrecognized underlying carcinoma, delays effective treatment of the carcinoma. A smear that establishes a diagnosis of cutaneous amebiasis, therefore, should be followed by biopsy to exclude or confirm an underlying carcinoma. PMID- 1621902 TI - [A biological rhythm approach to psychological correction of postural tone disorders in pregnant women with arterial hypotension]. AB - The studies have demonstrated a correcting and synchronizing effect of differentiated psychotherapy and dosed exercise on the maternal and fetal reactions to active postural load in women with gestational arterial hypotension, developing a blood circulatory disadaptation in the mother-fetus system and circadian desynchronization of the postural tone. Traditional physiopsychoprophylactic preparation to labor, carried out in the reference group of pregnant women, was of no avail in this respect. PMID- 1621903 TI - [Prevention of disorders of the functional state of blood coagulation and fetoplacental complex in pregnant women with late toxicosis]. AB - Analysis of the basic parameters of coagulogram and the fetoplacental system in pregnant women with late gestosis has lead the authors to a conclusion that chronic disseminated intravascular blood coagulation (DIC syndrome), frequently resulting in abnormal blood loss in the early postpartum period, develops in severe gestosis. Combined therapy with estrogens, rheopolyglucin, heparin, curantil, essentiale, administered for 6-8 days before delivery, normalized the hemostasis system and reduced uterine bleedings. PMID- 1621904 TI - [Circulating immune complexes and immunoglobulins A, M and G in the mother-fetus system in normal pregnancy and gestosis]. AB - Circulating immune complexes (CIC) and immunoglobulins A, M, and G were measured in the maternal peripheral blood, mixed umbilical blood, and amniotic fluid in women with normal pregnancy and gestosis. CIC concentrations in the examined fluids did not surpass the levels typical of healthy donors. Maternal blood CIC levels were higher in gestosis than in normal pregnancy, and CIC levels in the umbilical blood and amniotic fluid were always lower than in maternal blood serum. IgG levels were found the most shifted. These data evidence changes of the humoral immunity in normal pregnancy, this being, probably, one of the mechanisms providing its favorable course. PMID- 1621905 TI - [Doppler-metric and Doppler echocardiographic study of the nature and stage of disorders of fetal hemodynamics in intrauterine fetal growth retardation]. AB - Pregnancy course, labor outcome, and doppler-metric findings were analyzed in 174 women, 98 with normal pregnancy (controls) and 76 with small-for-date fetuses when examined on weeks 28-41; the aim of the study was to analyze the pattern of hemodynamic disorders in small-for-date fetuses. A classification of fetal hemodynamic disorders has been developed, that distinguishes three types of disorders differing in severity: first degree--disordered fetoplacental circulation not reaching the critical values and satisfactory fetal hemodynamics; second degree--compensated disorders of fetal hemodynamics; third degree- critical state of fetal hemodynamics. Use of this classification in clinical practice will help define rational strategy of pregnancy follow-up. PMID- 1621906 TI - [Biophysical activity of the fetus during labor in EPH-gestosis]. AB - Fetal respiratory and motor activities were studied in 105 parturients with EPH gestosis of varying severity and in 25 reference ones. The results evidence that, in contrast to the antenatal period, normal fetal condition in labor is associated with biophysical inertness, this fact confirming the known viewpoint on the intranatal fetal hibernation. Active management of labor in parturients with doubtful and abnormal biophysical parameters on the eve of delivery impairs the natural mechanisms of fetal defense in labor. Respiratory or motor activity of the fetus should be regarded as a prognostically unfavorable sign in respect of hypoxic involvement of the CNS and the newborn aspiration syndrome. PMID- 1621907 TI - [WHO activities in the area of adolescent reproductive health protection]. PMID- 1621908 TI - [Experience in the use of vaginal and intracervical enzaprost suppositories in preparation for labor]. AB - To improve the efficacy of prelabor treatment of pregnant women with some obstetrical abnormalities, such as over-term pregnancy, AB0- and Rh isosensitization, anemia, gestosis of the second half of pregnancy, vaginal and intracervical suppositories containing 0.1 mg of enzaprost were administered to 102 women for 1-5 days. In 30 (29.4%) cases such treatment induced spontaneous labor. In 64 (62.7%) women labor was induced by deoxy-amino oxytocin, and in 8 (7.8%) women this latter drug had to be administered repeatedly to induce labor. The babies born to the women under observation had the Apgar score of 6-10, 92 (90.2%) of them had the score of 8-10. No stillbirths or early infant mortality cases were recorded. Therefore prelabor treatment with vaginal or intracervical suppositories with enzaprost is effective and safe for both mother and newborn. PMID- 1621909 TI - [Effects of leukinferon on the phagocytic function of puerperal blood]. AB - Leukinferon effects on the phagocytic activities of the monocytes and polymorphonuclear leukocytes of 12 pregnant women and puerperants with various chronic infectious diseases were studied in vitro. Blood samples of 5 female donors were examined for control. It was found possible to stimulate and correct phagocytic function by leukinferon, proceeding from the initial function of the blood cells and the presence of serum factors. The immunocorrecting properties of leukinferon were found particularly valuable in cases with immunodeficiencies, for infectious diseases and labor complications could thus be prevented in this high-risk group of puerperants. PMID- 1621910 TI - [A combined reflex method in the treatment of suppurative-infectious diseases in the postpartum period]. AB - The purpose of this study was to develop an effective pathogenetically validated method for the treatment of puerperants with pyoseptic diseases, making use of reflex therapy, and clinical assessment of this method. The study has involved 190 puerperants, in 50 of them the postpartum period ran a normal course and the rest 140 developed pyoseptic complications. Case histories were analyzed, clinical and laboratory tests (blood proteins, Mancini's test for immunoglobulins, Dorofeichuk's blood plasma lysozyme test) were carried out. Vegetative regulation was studied with the use of a vegetative test kit. A method for reflex therapy of the detected disorders of the vegetative regulation associated with puerperal pyoseptic diseases has been developed, resulting in strengthening of the defense potential of the body. Clinical assessment of the method has confirmed its high efficacy. PMID- 1621911 TI - [Clinical-morphological parallels in postpartum endometritis]. AB - Clinicomorphologic parallels were studied in 45 puerperants with postpartum endometritis. This condition was histologically confirmed in 42 of the 45 patients with its clinical symptoms (in 100% of patients with the grave, in 95% with the medium-severity, and in 83% of those with the benign form of the disease). The authors came to the conclusion that the severity of postpartum endometritis was directly dependent on the extent and depth of the uterine wall involvement in the inflammatory process. By the end of treatment the morphologic signs of inflammation persisted in 40% of patients even without clinical signs of endometritis. Such women should be referred to a group at high risk of developing chronic endometritis. PMID- 1621912 TI - [Significance of catecholamine levels in the diagnosis and prognosis of dysadaptation of preterm newborn infants]. AB - Analysis of the clinical status of preterm newborns and the results of histochemical studies of the red cell catecholamine depositing function has led the authors to a conclusion that the Apgar score is reliable only in case of the newborn's critical condition. In slight and medium-severity asphyxia high red cell satiation with catecholamine granules was associated with a favorable outcome for the newborns. The authors claim that analysis of red cell catecholamine-depositing function is a sufficiently reliable diagnostic and prognostic criterion for the assessment of a preterm newborn's status. PMID- 1621913 TI - [Morphological analysis of the state of the ovaries of the newborn infants]. AB - Studies of 98 newborn ovaries included measurements of their mass, estimation of follicle number in a standard section size, of the integral parameter reflecting the total number of follicles in the ovary and the count of follicular cells adjacent to the oocyte in the primary follicle. The count of follicular cells was found to be a permanent value, not related to the newborn's mass; ovarian mass, number of follicles in a standard section, and the integral parameter were growing together with the newborn's mass, changing within the range from 900-1000 to 2500-4000 g, increasing particularly intensively within the body mass range of 1000 to 2500 g. In fetuses weighing 2500-4000 g, dead from multiple developmental defects, these characteristics are essentially lower than in those dead from birth injuries. PMID- 1621914 TI - [Fibrinogen metabolism in juvenile uterine bleeding]. AB - The levels of fibrinogen, monomeric fibrin soluble complexes (MFSC), fibrin fibrinogen degradation products (FDP), and the status of blood coagulation and fibrinolytic systems were studied in girls suffering from juvenile uterine bleedings. Fibrinogen and MFSC levels were found lowered and FDP concentration increased in such bleedings. Fibrinogen concentration correlated with the activities of the coagulating and fibrinolytic systems, and the MFSC level only with the coagulating system activity. Mathematical analysis has revealed a relationship between blood fibrinogen metabolism and the activities of the coagulating and fibrinolytic systems, whose functions in this condition are relatively autonomous. PMID- 1621915 TI - [Criteria for singling out groups of pregnant women at risk of obstetric complications]. PMID- 1621916 TI - [General principles of the pathogenesis of vegetovascular and psychoemotional disorders during menstrual cycle and methodological approaches to their study]. AB - Analysis of charts filled in by 79 women (mean age 31.5 +/- 4.0 years) over the course of 2-3 menstrual cycles has demonstrated the regular manifestation of various psychosomatovegetative symptoms over the entire course of the cycle (in the follicular, lutein phases, and during ovulation). Study of the brain electric activity and of the function of various sections of the autonomic nervous system, as well as examination of the emotional and mental sphere of the patients has revealed the contribution of the brain suprasegmental sections to the pathogenetic mechanisms of these disorders. PMID- 1621917 TI - [Incidence of gynecologic diseases in multiparae during the climacteric period]. AB - The structure and incidence of gynecologic diseases were studied in 796 women aged 40 to 60. The results were computer-processed. A significant (by 3.5 times) increase of the incidence of atrophic changes of the vagina and vulva and genital dystopia were revealed in multiparae, which fact evidenced unqualified labor management and neglect of hygienic measures in the postpartum period. Cervix uteri abnormalities were also more often detected in multiparae. A direct correlation between the number of pregnancies, deliveries, and abortions, on the one hand, and incidence of diseases of the cervix uteri, on the other, was revealed; uterine myoma was more frequently found in multiparae than in women who had one or two deliveries. A direct relationship was established between the duration of lactation period and incidence of ovarian tumors. Mammary diseases were more frequently detected in women with a history of one or two deliveries. PMID- 1621918 TI - [Macromastia]. PMID- 1621919 TI - [Ovarian and endometrial status in tubal and peritoneal sterility]. AB - A total of 97 patients with laparoscopically confirmed tubal and peritoneal sterility were examined. Thirty-six patients presented with a normal biphasic menstrual cycle, the rest 61 with the lutein phase insufficiency. Follicular presence and size were examined by ultrasonography, the dominant follicle and endometrium volumes were estimated. Only in 17 of the 97 examinees all the examined parameters were found normal, in the rest deviations from the normal echographic picture were revealed. More marked changes were detected in the patients with the lutein phase insufficiency. The findings evidenced a direct correlation between ultrasonic data and rectal temperature, adhesion process severity and the results of ovarian biopsy specimen histologic examination. The authors recommend ultrasonic examination for the assessment of ovarian function in patients suffering from tubal and peritoneal sterility. PMID- 1621921 TI - [Management of pregnancy and labor in obese women]. PMID- 1621920 TI - [Rectosigmoid vaginoplasty in children and adolescents]. AB - The authors analyze the results of vaginal plasty with grafts from the rectosigmoid portion of the large intestine, carried out in 279 girls aged 3 to 18 with abnormalities of the genitals and vaginal aplasia, including that with a functioning uterus. They have developed new modifications of such surgery, that facilitate sexual social adaptation of the patients when they reach puberty. PMID- 1621922 TI - [Moscow delivery asylums at the end of the 19th and beginning of the 20th centuries]. PMID- 1621923 TI - [Methodological approaches to early detection of benign epithelial tumors of the ovaries]. PMID- 1621924 TI - Neurological impairment in congenital bilateral ptosis with ophthalmoplegia. AB - A case is described of congenital bilateral ptosis and ophthalmoplegia due to incomplete bilateral paralysis of the third cranial nerve associated with dysmorphisms, brain malformations and epileptiform EEG abnormalities. We hypothesize that in our case the ophthalmological disturbance is due to mesencephalic impairment. In literature there are few reports of congenital bilateral paralysis of the third cranial nerve and they lack detailed MRI findings. We stress in patients with congenital third cranial nerve palsy the importance of thorough neurological investigations including prolonged wake-sleep EEG monitoring as well as CT scan and MRI to establish the origin of the disorder. PMID- 1621925 TI - Color Doppler flow imaging of CSF flow in an infant with intraventricular hemorrhage. AB - Evaluation of CSF flow was performed by means of the color Doppler flow imaging (CDFI) technique. The motion of CSF was examined in an infant with intraventricular hemorrhage (IVH). With the aid of CDFI, CSF flow in the aqueduct, 3rd ventricle and foramen of Monro could be demonstrated. CSF flow in both upward and downward directions was clearly visualized, primarily reflecting cardiac pulsation and respiration. When he was subjected with intermittent positive pressure ventilation, during inspiration there was upward flow in the aqueduct, while during expiration there was downward flow. Our experience indicates that CDFI is a useful technique for examining the CSF circulation in infants with IVH. PMID- 1621926 TI - Congenital focal muscle dysplasia in the lower extremities from probable abnormal innervation: a case report. AB - A two-year-seven-month-old girl with pes equinovarus congenita, muscle hypotonia and weakness limited to the lower extremities is presented. Upon admission to our hospital, she could stand with support but could not walk alone. Serum creatine kinase level was normal and the electromyogram was nondiagnostic. The muscle CT disclosed an almost total absence of bilateral vastus lateralis and medialis, rectus femoris and gastrocnemius muscles. The biopsied vastus lateralis muscle was almost completely replaced by fat tissue, and a small amount of muscle tissue showed uniform type 1 fiber and an aggregate of atrophic fibers in one fascicle. Because of an absence of progressive muscle weakness and neurogenic EMG findings, the authors conclude that the muscle pathology was due to the congenital anomalous condition of probable abnormal innervation to developing muscles. PMID- 1621927 TI - Hyperthyroid-induced chorea in an adolescent girl. AB - Hyperthyroidism is invariably accompanied by nervous system dysfunctions. Irritability, emotional lability and hyperkinesia are the signs and symptoms most frequently observed. Chorea or choreoathetosis are only rarely associated with hyperthyroidism. It is the purpose of this work to describe the case of a young girl in whom chorea was the main manifestation of thyrotoxicosis. The chorea receded and disappeared as the patient became euthyroid. Hyperthyroidism, therefore, is to be considered an unusual cause of chorea and every patient with choreiform movements should be examined also for thyroid function. PMID- 1621928 TI - Tongue dyskinesia in Wilson disease. PMID- 1621929 TI - Carrier detection of Duchenne/Becker muscular dystrophy: computer-assisted direct quantitation of gene amplification products. AB - An improved method by quantitative dystrophin gene deletion analysis was developed for the detection of Duchenne/Becker muscular dystrophy (DMD/BMD) carriers. Exon 52, which had been found to be deleted in DMD probands, was amplified for female family members, together with exon 60 as a reference, at the exponential phase of polymerase chain reaction. The products were separated by electrophoresis, the band intensities on gel photographs were quantitated, and the target/control ratios were calculated. The values for three heterozygous mothers were approximately half those for normal individuals and two definite non heterozygous mothers. This procedure is easy, rapid and useful for the carrier diagnosis of DMD/BMD. PMID- 1621930 TI - Selective involvement of the quadriceps muscle in congenital muscular dystrophies: an ultrasonographic study. AB - Muscle ultrasound scanning is a non-invasive and painless technique for evaluating muscle disorders in childhood. We have performed ultrasound scans of the quadriceps muscle in 26 children with various forms of congenital muscular dystrophies. There were 8 patients clearly showing selective involvement within the components of the quadriceps. In all cases showing selective involvement, the rectus femoris was spared and the vastus muscles were the affected group. Our findings support the concept of heterogeneity, often encountered in congenital muscular dystrophies. PMID- 1621931 TI - Factors influencing the clinical type and course of myasthenia gravis. AB - Myasthenia gravis is considered to be an autoimmune disease in which several factors reciprocally influence the clinical type and course. We investigated the relative importance of the following factors: anti-acetylcholine receptor antibody (AChR Ab), HLA, age at onset, autoimmunity, thymic abnormality, duration of treatment, change in AChR Ab titer and immunosuppressive therapy. The pretreatment-AChR Ab titer and HLA were shown to significantly influence the clinical type. On the other hand, the age at onset significantly influenced the clinical course. The finding that with an onset at less than 5-year-old there was a tendency for a good prognosis suggests an association between the immaturity of the muscle and immune systems, and the clinical course. PMID- 1621932 TI - Reduced brainstem size in children with autism. AB - Recently, structural brain abnormalities as well as functional abnormalities of the brainstem have been reported in autistic children. The authors undertook an analytic study of the brainstem in autistic children by means of magnetic resonance imaging (MRI). The MRI scans of 29 autistic children were compared with 15 control MRI scans. The autistic children were divided into two groups according to DQ (IQ) level: the DQ (IQ) greater than or equal to 80 group and the DQ (IQ) less than 80 group. The midbrain and pons were measured, and the ratio of the midbrain and pons sizes versus the cranium size were calculated. The brainstem size was found to be significantly smaller in the autistic group. In particular, the reduction in brainstem size tended to be greater in the low DQ (IQ) group when compared with the high DQ (IQ) one, though there was no significant difference (p less than 0.1). This suggests that the brainstem is anatomically altered in autistic children. PMID- 1621933 TI - The Rett girls with preserved speech. AB - In addition to a total population of 102 classic Rett syndrome girls who visited our department in the last 8 years, 3 were observed showing some of the features typical of this syndrome, including hand-washing activities, but also some atypical features, the most notable of which was their ability to speak in fully formed phrases. One of these girls has a sister with the typical features of classic Rett syndrome. Atypical variants of the Rett syndrome are discussed and the possibility of a "speaking" variant is considered. PMID- 1621934 TI - International Consensus Report on Diagnosis and Management of Asthma. International Asthma Management Project. PMID- 1621935 TI - A quality improvement process team. PMID- 1621936 TI - Successful implementation of a CQI process. AB - Managers and CQI facilitators must be equipped to understand both the pain and joy inherent in the organizational change process. The organizational caveats associated with successful implementation of CQI include the following: Expect resistance to change, especially if your current situation is comfortable. Be patient--the change process is an evolution, not a revolution. Plan well in a multidimensional format--you are changing more than policies and procedures when adopting CQI. Shape a culture that will support CQI, actively plan to expand communication opportunities, enhance training programs, and increase recognition modalities. Anticipate and deal with the stress that will accompany change. Don't forget to celebrate successes as transformation occurs! PMID- 1621938 TI - Approaches to quality improvement. PMID- 1621937 TI - Overcoming skepticism about quality improvement. PMID- 1621939 TI - From QA to CQI: a retrospective review. PMID- 1621940 TI - Some implications of CQI for nursing administration. PMID- 1621941 TI - A quality initiative for enterostomal therapy nursing. PMID- 1621942 TI - Quality improvement: the nurse's role. AB - Continuous quality improvement is a concept which includes: Quality assurance- the provision of services that meet an appropriate standard. Problem resolution- including all departments involved in the issue at hand. Quality improvement--a continuous process involving all levels of the organization working together across departmental lines to produce better services for health care clients. Deming (1982b) and others have espoused total system reform to achieve quality improvement--not merely altering the current system, but radically changing it. It must be assumed that those who provide services at the staff level are acting in good faith and are not willfully failing to do what is correct (Berwick, 1991). Those who perform direct services are in an excellent position to identify the need for change in service delivery processes. Based on this premise, the staff nurse--who is at the heart of the system--is the best person to assess the status of health care services and to work toward improving the processes by which these services are provided to clients in the health care setting. The nurse manager must structure the work setting to facilitate the staff nurse's ability to undertake constructive action for improving care. The use of quality circles, quality councils, or quality improvement forums to facilitate the coordination of quality improvement efforts is an effective way to achieve success. The QA coordinator assists departments in documenting that the quality improvement efforts are effective across all departments of the organization, and aggregates data to demonstrate that they meet the requirements of external regulatory agencies, insurers, and professional standards. The nurse executive provides the vision and secures the necessary resources to ensure that the organization's quality improvement efforts are successful. By inspiring and empowering the staff in their efforts to improve the process by which health care is provided, nurse managers participate in reshaping the health care environment. The professional nurse plays a vital role in the quality improvement of health care services. However, nurses cannot make these improvements in a vacuum; they must include other professionals and ancillary personnel in their efforts. Total quality commitment must include all levels of an organization's structure. Quality patient care services will be achieved as the result of positive interactions among departments working together to build a dynamic mechanism that continuously improves the processes and outcomes of health care services. PMID- 1621943 TI - From QA to QI in a home health agency. PMID- 1621944 TI - Measurement and standards in continuous quality improvement. AB - So where does all of this lead us? Many QA professionals are currently concerned that CQI will displace their role. Nurses are concerned that they will have to learn an entirely new process and language. In a National Association of Quality Assurance Professionals position paper, Martin (1990) points out that CQI builds on and strengthens the weaknesses of traditional quality assurance approaches. Quality improvement is not a substitute for quality assurance; it is a supplement to expand health care providers' understanding of the components of excellent patient care. Change and variation surrounds us at all times. Continuous quality improvement teaches the premises of variation and change. Through a better understanding of variation and application of this understanding to continuous improvement of the system of care, we will help assure better outcomes for our clients. Nurse administrators and staff nurses should endorse the arrival of continuous quality improvement. As leaders in QA, we are indeed positioned to become leaders in CQI. PMID- 1621945 TI - Using the long-term care minimum data set as a tool for CQI in nursing homes. PMID- 1621946 TI - Purification of sheep immunoglobin G using protein A trapped in sol-gel glass. AB - An effective method for purifying immunoglobulins has been developed utilizing a sol-gel glass support system. Sol-gel glass is an effective support for chemically active ligands entrapped in this medium at room temperature. There are two problems associated with the utilization of such sol-gel glasses for entrapping macromolecules. One is the phenomenon of nonspecific absorption of proteins onto the glass. The second is that only a portion of the entrapped molecules may retain their biological activity. In the present study a sol-gel glass was treated with gamma-aminopropyltriethoxysilane to provide a matrix that eliminated nonspecific absorption of proteins. The method of entrapping molecules was modified to increase the proportion of entrapped molecules that retained their reactivity. Protein A was entrapped in the modified sol-gel glass column and used to purify IgG from sheep sera by affinity chromatography. The purity of the IgG, as determined by SDS-PAGE, was comparable to that obtained from commercially available protein A columns and, if the capacity of the column was not exceeded, the yield approached 100%. Although the quality and quantity of the yields were comparable, the methodology described herein can be accomplished more rapidly and with greater ease. Furthermore, the sol-gel glass ligand preparation is extremely stable and can be reused for isolation of gamma-globulin. The technique has great potential for isolating macromolecules utilizing various ligands. PMID- 1621947 TI - Subtraction of background fluorescence in multiharmonic frequency-domain fluorimetry. AB - Background fluorescence is a major concern in time-resolved microfluorimetry studies of biological samples. A general method for subtraction of an arbitrary background signal in measurements of lifetime and anisotropy decay by multiharmonic Fourier transform spectroscopy is presented. Multifrequency phase and modulation values are measured in parallel by transformation of digitized time-domain waveforms into the frequency domain. For subtraction of background, time-domain waveforms are acquired for emission and reference photomultipliers for sample (e.g., cell containing fluorophore) and blank (e.g., unlabeled cell). Time-domain waveforms obtained in a series of measurements (e.g., sample and blank for parallel and perpendicular orientations of an emission polarizer) are time-justified by least-squares fitting of reference channel waveforms or by phase comparison of the first Fourier harmonics of the reference channel. Background is then subtracted directly in the time domain, and the subtracted waveform is Fourier transformed to the frequency domain for analysis of lifetime or anisotropy decay. This approach yielded excellent background correction over a wide range of background intensities and decay profiles. The method was tested in cuvette fluorimetry with fluorescein and acridine orange and in fluorescence microscopy with living MDCK cells loaded with the pH indicator BCECF. Sample lifetimes and rotational parameters could be recovered accurately with greater than 50% of the signal arising from background. These results establish a direct and practical approach to subtraction of background in complex biological and chemical samples studied by frequency-domain fluorimetry. PMID- 1621948 TI - Monitoring gene expression in Chinese hamster ovary cells using secreted apoaequorin. AB - A luminescence method for monitoring gene expression in Chinese hamster ovary cells using apoaequorin as a secreted reporter enzyme is described. In this method, the cell is not disrupted prior to assay as in the earlier aequorin procedure and in the firefly method. The apoaequorin secretion vector is constructed by fusing the DNA fragment of the signal peptide sequence of human follistatin to the apoaequorin gene. Transfection of Chinese hamster ovary cells with the vector causes the apoaequorin to be secreted directly into the culture medium. Assay is carried out by removing a small aliquot of the culture medium, incubating it with coelenterazine, and adding Ca2+ to trigger light emission from the regenerated aequorin. The light intensity is measured with a photomultiplier photometer and is proportional to the amount of apoaequorin present. The method is highly specific and sensitive and can be carried out in a relatively short period of time. PMID- 1621949 TI - Bound and determined: a computer program for making buffers of defined ion concentrations. AB - A computer program that allows the preparation of buffers containing known concentrations of metal-ligand complexes at defined pH values and temperatures is described. Ligands are defined as compounds that bind metals and may include AMP, ADP, ATP, GMP, GDP, GTP, EGTA, EDTA, BAPTA, phosphate, sulfate, chloride, monocarboxylic acids, dicarboxylic acids, organophosphates, and/or citric acid. Metals may include sodium, potassium, magnesium, calcium, and/or manganese. The program uses association constants corrected for temperature and ionic strength so that solutions between 0 and 40 degrees C and between pH values of 4 and 10 can be defined. The program can perform the following: (i) calculate the concentration of all metal-ligand complexes when total metal and total ligand concentrations are known, (ii) calculate the concentration of metal ion required to make a solution of known free metal ion concentration when total ligand concentrations are known, (iii) calculate the concentration of ligand required to make a solution of known free metal ion concentration when total metal concentrations are known, and (iv) calculate the total concentrations of metal and ligand required to make a buffer of known metal-ligand concentration. Options i-iii are useful for making buffers of defined free metal ion concentrations; option iv is useful for making buffers of defined metal-nucleotide concentrations. PMID- 1621950 TI - Detection of 8-hydroxyguanine in small amounts of DNA by 32P postlabeling. AB - A method for the sensitive detection of 8-hydroxyguanine residues in small amounts of DNA (0.2-2 micrograms) was developed. It comprises (i) the enzymatic hydrolysis of DNA to 2'-deoxyribonucleotide 3'-monophosphates, (ii) degradation of the bulk amount of normal purine and pyrimidine deoxyribonucleotides in the DNA digest by treatment with trifluoroacetic acid and hydrazine, respectively, under conditions retaining the structure of d(8-OH-G)p necessary for 5' phosphorylation by T4 polynucleotide kinase (PNK), (iii) 5' phosphorylation of d(8-OH-G)p by T4 PNK-catalyzed transfer of 32P from [gamma-32P]ATP, and (iv) 2D thin-layer chromatography on polyethyleneimine-cellulose sheets to purify and resolve 32P-postlabeled d(8-OH-G)p. Model experiments with mixtures composed of synthesized d(8-OH-G)p and DNA hydrolysate indicate that it is possible to detect one 8-hydroxyguanine residue out of 2 x 10(6) normal bases starting with 1 microgram DNA. The methodology, which allows for a further decrease of this detection limit, might be very useful for the sensitive detection of DNA damage induced by activated oxygen species in small amounts of DNA. We demonstrate the formation of 8-OH-G in DNA in vitro by low doses of 60Co gamma-rays. PMID- 1621951 TI - One-hour downward alkaline capillary transfer for blotting of DNA and RNA. AB - The downward alkaline capillary transfer of DNA and RNA from agarose gel to a hybridization membrane was performed using a transfer solution containing 3 M NaCl and 8 mM NaOH. Under mild alkaline conditions, DNA and RNA were completely eluted from the agarose gel and bound to a hybridization membrane within 1 h. On the basis of this new method of transfer a blotting protocol, downward alkaline blotting, was elaborated. It provides a fast and efficient alternative to commonly used Southern and Northern blotting protocols. The downward alkaline blotting of DNA and RNA can be completed in 2.5 and 1.5 h, respectively, and can be used with both plastic and nitrocellulose membranes. In addition, the downward alkaline blotting protocol allows for a hybridization efficiency of DNA and RNA higher than that of the standard blotting protocols performed at neutral pH. PMID- 1621952 TI - The synthesis of high-specific-activity UDP-[6-3H]galactose, UDP-N-[6 3H]acetylgalactosamine, and their corresponding monosaccharides. AB - Tritiated uridine-5'-diphosphogalactose (UDP-[3H]Gal) has been widely used to study oligosaccharide biosynthesis and structure. It can be synthesized either chemically or enzymatically using galactose oxidase to oxidize the hydroxyl moiety at C-6 to an aldehyde (6-aldo-UDP-Gal), which is then reduced back to the alcohol with tritiated sodium borohydride. Although the enzymatic approach is simple and efficient, there are several problems associated with it. First, incomplete oxidation to the aldehyde reduces the final specific activity. Second, if the galactose oxidase is not removed from the 6-aldo-UDP-Gal prior to reduction, the resulting UDP-[6-3H]Gal can be reoxidized to 6-aldo-UDP-[6-3H]Gal. We present evidence for the occurrence of this compound in one commercially obtained preparation of UDP-[6-3H]Gal. Finally, if an excess of 6-aldo-UDP-Gal is used for good yield, it is necessary to quench the reduction with nonradioactive borohydride, again reducing the final specific activity. We have devised a rapid, inexpensive, and efficient synthesis of UDP-[6-3H]Gal that circumvents all of these problems. Galactose oxidase is used to produce 6-aldo-UDP-Gal and the completeness of this reaction is confirmed on polyethyleneimine (PEI) cellulose TLC plates. The 6-aldo-UDP-Gal is purified on silica gel 60 TLC plates. This purified compound is then reduced with tritiated sodium borohydride, with the aldehyde present in excess. Unreacted 6-aldo-UDP-Gal is then purified away from the product UDP-[6-3H]Gal by chromatography on PEI cellulose. Radiochemically pure UDP-[6-3H]Gal with a specific activity of 10 Ci/mmol was obtained using the above scheme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621953 TI - Determination of cysteine plus half-cystine in protein and peptide hydrolysates: use of dithiodiglycolic acid and phenylisothiocyanate derivatization. AB - Cysteine and half-cystine in proteins and peptides can be determined by acid hydrolysis in the presence of dithiodiglycolic acid, derivatization with phenyl isothiocyanate, and HPLC separation of the phenylthiocarbamyl amino acids. The determination requires no additional sample handling, oxidation, reduction, alkylation, or desalting. Samples containing cystine are treated in the same manner as those containing cysteine. Derivatization of cysteine or half-cystine by dithiodiglycolic acid has no effect on any other amino acids. Recovery of the PTC-cysteine derivative is greater than 90% over the linear range of 5 pmol to 1 nmol. Precision of the cysteine plus half-cystine determination is equivalent to that observed for all other amino acids. Structure work on the derivative indicates that it is a mixed disulfide containing cysteine and thioglycolic acid. PMID- 1621954 TI - Detection and possible origins of aminomalonic acid in protein hydrolysates. AB - Aminomalonic acid (Ama) was first detected in alkaline hydrolysates of proteins in 1984. In this work we describe our search for the origin of aminomalonic acid in alkaline hydrolysates of proteins. We have developed a technique for quantitation of aminomalonic acid based upon gas chromatography/mass spectrometry. Using this technique, we find approximately 0.3 Ama/1000 amino acids in hydrolysates of Escherichia coli protein. We have demonstrated that Ama is not formed from any of the 20 major amino acids during the hydrolysis procedure. Furthermore, the amount of Ama found does not depend on the presence of small amounts of O2 during the hydrolysis. Thus far, we have not been able to demonstrate an artifactual origin for Ama. The results described above suggest that Ama may indeed be a constituent of proteins before the hydrolysis procedure. Possible origins of Ama include errors in protein synthesis and oxidative damage to amino acid residues in proteins. PMID- 1621955 TI - Magnetic bead purification of M13 DNA sequencing templates. AB - A method for the preparation of multiple M13 DNA sequencing templates is described. No phenol extraction is required and the procedure can be carried out in Eppendorf tubes or 96-well microtiter plates. Starting with a phage supernatant, the entire procedure is carried out in the same reaction vessel and all separation steps are based on a novel application of magnetic bead separation. The design of a 96-well magnetic separator is presented and the application of the method for large-scale sequencing is discussed. PMID- 1621956 TI - A semi-micromethod for the determination of the extinction coefficients of duplex and single-stranded DNA. AB - We have developed a rapid and convenient procedure for the determination of concentrations and extinction coefficients of oligo- and polynucleotides. It offers significant advantages over other methods in terms of precision and the ability to detect artifactual or erroneous results. Samples are first completely digested with appropriate enzymes to mononucleotides and nucleosides. Using the multicomponent linear regression capabilities of commonly available spreadsheet programs, the absorbance spectrum of the digest can be analyzed as a linear combination of the contribution of the possible constituent monomers. If all the spectral components present have been included, the analysis yields the concentration of each of the monomer species whose sum is the concentration (in monomer units) of the original undigested sample. When combined with the predigest absorbance spectrum, the extinction coefficients of the intact sample can then be calculated. The analysis also yields the fractional base composition of the oligomer or polymer. The extensive spectral data provided by digital read outs of modern spectrophotometers permit the application of sensitive tests of the goodness of fit, thus facilitating the detection of artifacts and sample inhomogeneity. Both single-strand and duplex structures can be analyzed comfortably in sample sizes of 25 to 35 nmol (total) of mononucleotides with a precision of 1%. The concentrations obtained by this method agree, on the average, within 0.2% with those determined by phosphate analysis of the same sample. The method also yields the base composition with an accuracy of ca. 5% for high-molecular-weight polymers and 2% for short oligomers (15-20 bp) when compared to the predicted values. PMID- 1621957 TI - Sulfone-aromatic ligands for thiophilic adsorption chromatography: purification of human and mouse immunoglobulins. AB - New thiophilic matrices and new procedures were used for the purification of immunoglobulins both from human serum and from hybridoma cell cultures containing fetal calf serum. A range of aromatic and heteroaromatic ligands containing hydroxyl or amino groups have been coupled to divinyl sulfone-activated agarose. The resulting affinity matrices have the general formula M-O-CH2-CH2-SO2-CH2-CH2 X-Y, where M is the agarose matrix, X is oxygen or nitrogen, and Y is an aromatic or heteroaromatic compound. Contrary to earlier expectations these matrices showed pronounced thiophilic binding patterns when tested for the selective binding of immunoglobulins from human serum. The binding is influenced by the structure of the aromatic part of the ligand, the ligand concentration, and the concentration and type of lyotropic salt. 2-Hydroxypyridine coupled to divinyl sulfone-activated agarose was used to purify murine monoclonal antibodies (IgG1 and IgM) from hybridoma cell cultures containing fetal calf serum. Compared to previous methods, significantly increased binding capacity (300-1500%) was obtained by using 1.0-1.2 M ammonium sulfate. Purity of the monoclonal antibody may be optimized for each individual clone by washing the column with either a low concentration of ammonium sulfate or polyethylene glycol before elution. PMID- 1621958 TI - Simultaneous electroelution of proteins from denaturing or native gels into a well matrix. AB - An electroelution device that is based on a semidry blotter and that allows the simultaneous elution of proteins or other charged macromolecules from one dimensional gels is described. It consists of a central plate that has a matrix of oblong wells arranged in eight columns of 32 wells each, such that when a gel is placed on the plate each lane of bands is underlaid by a column of wells. The plate is placed between the electrodes of a semidry blotter and the wells are sealed by a dialysis membrane resting on polyacrylamide gel block, prior to being filled with transfer buffer. Using radiolabeled molecular weight standards resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, elution is shown to require 30-60 min for 90% or better of proteins between 10 and 120 kDa to be removed from the gel. The recovery volume is 200 microliters per well and losses due to adsorption onto the dialysis membrane are minimal. beta Galactosidase eluted from a nonreducing, nondenaturing gel was shown to be quantitatively active. The advantages of the device include its ease of assembly and operation, its speed, its reproducibility, and the fact that no gel slicing is required since all proteins are eluted simultaneously, allowing large-scale screening of multiple protein fractions. PMID- 1621959 TI - A colorimetric method for the quantitation of uronic acids and a specific assay for galacturonic acid. AB - A method of quantitating uronic acids and uronic acids from pectin in particular is described. The method uses carbazole in 80% sulfuric acid with borate ions added. The assay is carried out at 60 degrees C. This assay has some cross reactivity with aldose sugars and must be timed precisely. A further method that is specific for galacturonic acid is also described. This method uses concentrated sulfuric acid and carbazole only. Of the biological substances tested, only formaldehyde and glyceraldehyde showed a reactivity of more than 10% that of galacturonic acid on a weight to weight basis. PMID- 1621960 TI - para-sulfobenzoyloxybromobimane: a new membrane-impermeable reagent useful for the analysis of thiols and their export from cells. AB - para-Sulfonylbenzoyloxybromobimane (sBBr) was shown to be similar to the fluorescent labeling agent monobromobimane (mBBr) in reacting rapidly and selectively with thiols to produce stable derivatives which are readily separated by HPLC. Chromatography of the sBBr derivative provides a useful means of confirming the identification of an unknown thiol based upon the chromatography of its mBBr derivative and can be useful for quantitative determination of polycationic thiols for which chromatography of the mBBr derivative is unsatisfactory. Unlike mBBr, which readily penetrates cells, sBBr was found not to be taken up by cells. These characteristics allow sBBr to be used, in conjunction with mBBr, to quantify the export of thiols from cells, as illustrated for GSH and the radioprotective drug WR1065, from V79 cells. Simultaneous determination of GSH and glutathione disulfides in cell culture medium could be achieved by labeling of thiols with sBBr followed by reduction of disulfides with dithiothreitol, labeling of the resulting thiols with mBBr, and HPLC analysis for both glutathione derivatives. PMID- 1621961 TI - Deuterium exchange on micrograms of proteins by attenuated total reflection Fourier transform infrared spectroscopy on silver halide fiber. AB - We illustrate the use of polycrystalline silver halide fibers (2-20 microns transparency range) for attenuated total internal reflection Fourier transform infrared (IR) spectroscopic measurements of microsamples (10 micrograms of protein). A powerful adjunct technique is a simple method for carrying out deuterium for proton exchange. Spectra of trypsin, soybean trypsin inhibitor, and their complex are easily obtained. Two kinds of difference spectra (DS) are revealing: DS1 (changes in protein on combination with ligand), IR of the trypsin soybean trypsin inhibitor complex (T.SBTI complex)--sigma [IR of trypsin (T) + IR of soybean trypsin inhibitor (SBTI)], the small values at all wavelengths indicating no conformational change of the proteins upon complexation, and DS2 (changes in materials on deuteration), IR of protioprotein--IR of deuterioprotein, which reveals the infrared bands affected by deuteration. The rate and the extent of the exchange are additional valuable parameters readily measured with this technique. In the present instance, the rate and the amount of the exchange for T.SBTI complex after 30 min was substantially less than that expected from the simple sum of the same parameters for the two individual proteins, T and SBTI. The enzymatic activity of trypsin on the fiber survived for more than a day, no autodegradation being detected by SDS-gel electrophoresis. PMID- 1621962 TI - The determination of intracellular sodium concentration in human red blood cells: nuclear magnetic resonance measurements. AB - The intracellular sodium concentration and intracellular volume of human red blood cells were determined from 23Na and 1H NMR spectra. It is shown that sodium dissolved in the intracellular water has a concentration higher than that previously published. The intracellular sodium concentration measured was 11.4 +/ 3.1 mM. A comparison of different NMR methods used to determine sodium concentration is given. PMID- 1621963 TI - Radioactive assay of 2,4-dienoyl-coenzyme A reductase. AB - A radioactive method for assaying 2,4-dienoyl-CoA reductase, also referred to as 4-enoyl-CoA reductase (EC 1.3.1.34), is described. The assay measures the incorporation of tritium from [4B-3H]NADPH into 2-trans,4-cis-decadienoyl-CoA or 2-trans,4-trans-decadienoyl-CoA which, after cleavage of the thioester bond with hydroxylamine, can be separated from the radioactive coenzyme by extraction with toluene. This assay is at least 30 times more sensitive than the spectrophotometric assay, even though rates determined by the radioactive method are 10 times lower than rates obtained spectrophotometrically due to a primary kinetic isotope effect. The linearity of this assay with respect to time and protein concentration is sufficient for determining 2,4-dienoyl-CoA reductase activities in extracts from small samples of human fibroblasts, which were found to contain reductase activities between 1.8 and 5.8 mU/mg of protein. PMID- 1621964 TI - Mechanical detection of interaction of small specific ligands with proteins and DNA in cross-linked samples. AB - Cross-linked crystalline and amorphous films of different proteins and cross linked DNA gels were found to change their mechanical properties when soaked in solutions of specific ligands at nearly physiological concentrations. This chemomechanical effect may be used to rapidly (within a few minutes) detect the ability of macromolecules to bind small (less than 1 kDa) ligand molecules, to measure concentrations of ligands (higher than 10 nM), and to estimate binding constants (lower than 10(7) M-1). Only 0.1-1 mg of protein or DNA is needed to prepare more than 10 samples sufficient for a large number of tests, provided binding is reversible. The method is recommended for rapid primary screening in search of new drugs, in biochemical studies, and as a basis for designing biosensors and other analytical instruments. PMID- 1621965 TI - Quantification and comparison of chloramphenicol acetyltransferase activity in transformed plant protoplasts using high-performance liquid chromatography- and radioisotope-based assays. AB - Rice and petunia leaf and cell suspension protoplasts were transformed by electroporation in the presence of pDW2. This plasmid contains a chloramphenicol acetyltransferase (CAT) coding region under the control of a promoter constructed from sequences of the cauliflower mosaic virus genome. We have compared two different approaches to measuring CAT activity in this system, namely high performance liquid chromatography (HPLC) and a radioisotope-based method. Our results show that both techniques have a similar detection limit of 10 mU CAT and (with an activity greater than 10 mU CAT) the standard error for measuring known amounts of CAT activity was less than +/- 12% for both assays. The HPLC technique, however, has a greater linear response range of 10-600 mU CAT than the radioisotope method, which has a range of 10-400 mU CAT. The HPLC assay also requires a shorter assay time. As a result of this work we believe that HPLC is a viable alternative to the radioisotope-based assay described. PMID- 1621966 TI - Evaluation of aminolysis of anilinothiazolinones to phenylthiocarbamoyl amino acid methyl amides as an alternative conversion method in protein sequencing. AB - The aminolysis of products of sequential degradation of proteins and peptides by methylamine is an alternative method of conversion of the unstable 5-alkyl-2 anilino-4-thiazolinones into the stable methyl amides of N alpha phenylthiocarbamoyl amino acids. The volatility of methylamine permits use in the gas phase during both manual and automatic sequential degradation. Two procedures were studied: (mode A) aminolysis by methylamine in the sequencer reaction chamber after liberation of the thiazolinones by trifluoroacetic acid and (mode B) aminolysis by methylamine vapors passed through a 1-chlorobutane solution of thiazolinones in the conversion flask of the sequencer. The sequencing program was modified for both procedures by making use of the standard sequencer functions. The yields of aminolysis in the conversion flask (mode B) are comparable to those obtained by standard conversion in 25% trifluoracetic acid and the procedure does not affect the repetitive yield. Aminolysis on the glass filter (mode A) requires a major modification of the degradation process, yet gives higher yields of the degraded amino acid derivatives. A disadvantage of both procedures, especially of mode A, is the presence of N-methyl-N' phenylthiourea in the methyl amide samples. We have not been able to achieve the expected improvement of the yields of degraded hydroxy amino acids. Therefore the replacement of acid conversion of anilinothiazolinones to phenylthiohydantiones by aminolysis for routine degradation cannot be recommended. High yields of methyl amides make aminolysis a promising candidate for the incorporation of fluorescent or other labels in the products of sequencing degradation. PMID- 1621967 TI - The structure of glutaraldehyde in aqueous solution determined by ultraviolet absorption and light scattering. AB - The structure of glutaraldehyde (GA) in aqueous solutions has been the subject of much debate. Since there were fundamental problems in the experiments in the preceding studies, in this article, the structure of GA was investigated with uv absorption and light scattering to avoid those problems. It was discovered that 70% glutaraldehyde solution contains a large quantity of polymeric species with cyclic hemiacetal structure. On dilution, the polymerized glutaraldehyde slowly converted to monomers. In dilute solution, glutaraldehyde is almost monomeric at pH 3-8, the major portion taking the cyclic hemiacetal structure. The structure of GA in 20% solution is similar to that in more dilute solution. alpha, beta Unsaturated structure does not exist in aqueous solution regardless of the concentration of glutaraldehyde. PMID- 1621968 TI - Microanalysis of beta-cyclodextrin and glucosyl-beta-cyclodextrin in human plasma by high-performance liquid chromatography with pulsed amperometric detection. AB - High-performance liquid chromatography with pulsed amperometric detection was applied to the determination of beta-cyclodextrin (beta-CD) and glucosyl (G)-beta CD in human plasma. They were well resolved from each other and from background components of plasma on a polymer-based reversed-phase column with 0.6% acetonitrile aqueous solution containing 1 mM sodium hydroxide as an eluent. The samples in the effluent were detected with a pulsed amperometric detector after postcolumn alkalization. The detection limits of beta-CD and G-beta-CD in plasma at a signal-to-noise ratio of 3 were 11 and 5 pmol, respectively. PMID- 1621969 TI - Trypsin-induced lysis of lipid vesicles: effect of surface charge and lipid composition. AB - We have made a curious observation that the proteolytic enzyme, trypsin, induced a rapid and complete release of the contents of vesicles composed of dioleoylphosphatidylethanolamine (DOPE) and oleic acid (OA). Content release at 37 degrees C, monitored by the release of an entrapped fluorescence marker (calcein), was accompanied by an extensive vesicle aggregation. The lytic activity of trypsin on the vesicles depended on pH and liposome composition. The optimal pH for vesicle lysis was below pH 7.4, which was different from the optimal pH for catalytic activity of trypsin. The lytic activity of trypsin was specific for vesicles composed of DOPE and fatty acids such as OA and palmitoleic acid; vesicles composed of dioleoylphosphatidylcholine, N-methyl-DOPE, and OA, or DOPE combined with other negatively charged lipids such as phosphatidylserine and phosphatidic acid were not sensitive to trypsin. Inhibition of enzyme activity by trypsin inhibitors did not abolish the lytic activity, suggesting that the lytic activity of trypsin is not related to the catalytic activity. However, the lytic activity of trypsin on vesicles composed of DOPE and OA was inhibited in the presence of excess vesicles containing negative charges, or by a pretreatment of trypsin with acylating reagent to reduce the positive-charge content of trypsin. These data demonstrate that vesicle aggregation and lysis are the results of electrostatic interactions of positive charges on trypsin and negative charges on the vesicles. Phase separation and transition to nonbilayer phases of the vesicle lipids are likely involved. PMID- 1621970 TI - Design and implementation of a particle concentration fluorescence method for the detection of HIV-1 protease inhibitors. AB - A critical step in the replicative cycle of the human immunodeficiency virus HIV 1 involves the proteolytic processing of the polyprotein products Prgag and Prgag pol that are encoded by the gag and pol genes in the viral genome. Inhibitors of this processing step have the potential to be important therapeutic agents in the management of acquired immunodeficiency syndrome. Current assays for inhibitors of HIV-1 protease are slow, cumbersome, or susceptible to interference by test compounds. An approach to the generation of a rapid, sensitive assay for HIV-1 protease inhibitors that is devoid of interference problems is to use a capture system which allows for isolation of the products from the reaction mixture prior to signal quantitation. In this paper, we describe a novel method for the detection of HIV-1 protease inhibitors utilizing the concept of particle concentration fluorescence. Our approach involves the use of the HIV-1 protease peptide substrate Ser-Gln-Asn-Tyr-Pro-Ile-Val which has been modified to contain a biotin moiety on one side and a fluorescein reporter molecule on the other side of the scissile Tyr-Pro bond. This substrate is efficiently cleaved by the HIV-1 protease and the reaction can be readily quantitated. Known inhibitors of the protease were readily detected using this new assay. In addition, this approach is compatible with existing instrumentation in use for broad screening and is highly sensitive, accurate, and reproducible. PMID- 1621971 TI - 31P NMR analysis of red blood cell UDPGlucose and UDPGalactose: comparison with HPLC and enzymatic methods. AB - The levels of uridine diphosphogalactose (UDPGal) and uridine diphosphoglucose (UDPGlu) in trichloroacetic acid extracts of human red blood cells (RBC) were measured by 31P NMR spectroscopy. Individual determinations were compared to results obtained by enzymatic and high-pressure liquid chromatographic (HPLC) methods. The characteristic doublet of the P beta resonance signals of both UDPGal and UDPGlu were detected in proton-decoupled spectra of extracts. Quantitative analyses were obtained by employing a standard, methylene diphosphonate, in an external capillary tube during data acquisition for periods of 14 to 24 h using an "inverse-gated" pulse sequence. The ratio of the integrated area of each of the uridine sugar nucleotide doublets to the area of the external reference peak was linear with concentrations between 0.03 and 0.50 mM. There was no difference between the mean value obtained by 31P NMR of 6.6 +/- 1.4 mumol UDPGlu/100 g Hgb or 2.1 +/- 0.6 mumol UDPGal/100 gHgb and the corresponding levels determined enzymatically or by HPLC in identical RBC extracts. When analyzed as paired data, only UDPGlu by NMR was found to be lower than the value obtained by HPLC. As a quantitative analytical tool, NMR spectrometry validated both the enzymatic and HPLC methods used for measurement of uridine sugar nucleotides in our laboratories. PMID- 1621972 TI - Detection of nicotinic receptor ligands with a light addressable potentiometric sensor. AB - The nicotinic acetylcholine receptor, purified from Torpedo electric organ, was coupled to a light addressable potentiometric sensor (LAPS) to form a LAPS receptor biosensor. Receptor-ligand complexes containing biotin and urease were captured on a biotinylated nitrocellulose membrane via a streptavidin bridge and detected with a silicon-based sensor. Competition between biotinylated alpha bungarotoxin and nonbiotinylated ligands formed the basis of this assay. This biosensor detected both agonists (acetylcholine, carbamylcholine, succinylcholine, suberyldicholine, and nicotine) and competitive antagonists (d tubocurarine, alpha-bungarotoxin, and alpha-Naja toxin) of the receptor with affinities comparable to those obtained using radioactive ligand binding assays. Consistent with agonist-induced desensitization of the receptor, the LAPS receptor biosensor reported a time-dependent increase in affinity for the agonist carbamylcholine as expected, but not for the antagonists. PMID- 1621973 TI - A specific and inexpensive assay of radiolabeled long-chain acyl-coenzyme A in isolated hepatocytes. AB - A simple procedure for determining radiolabeled long-chain acyl-CoA levels in isolated rat hepatocytes has been developed. It consists of a classical extraction of long-chain acyl-CoAs after preliminary removal of the excess labeled free fatty acid. A two-step TLC purification ensures elimination of long chain acylcarnitine, the main interferent in most methods, and other common lipids. The purity of the acyl-CoA was confirmed by a second TLC system and by spectral analysis. Overall recovery was approximately 70%. PMID- 1621974 TI - A group additivity model for analyzing absorption spectra of organic compounds: applications to partial structural analysis and molecular weight determinations of polymers, nucleotides, and peptides. AB - A new method for the analysis of organic structural groups from absorption spectra is described. The method is based on the integrated intensity of absorption. It requires only micrograms of analyzed compound, which may be fully recovered after analysis from its solution. The method can be used for different kinds of structural and/or kinetic studies. For example, the reaction kinetics and tautomeric equilibria can be easily studied by this method. The method can also be used for the determination of molecular weight and quantitative composition of polymers, nucleotides, and/or peptides. Hydrolysis or derivatization of the studied compounds is not necessary. On the basis of this method, automatic molecular weight, nucleotide, and peptide analyzers can be constructed. PMID- 1621975 TI - Solid-phase time-resolved fluorescence detection of human immunodeficiency virus polymerase chain reaction amplification products. AB - A new assay system for the detection of polymerase chain reaction (PCR) amplification products is presented. This single-pot sandwich assay system employs solid-support oligonucleotide-coated capture beads, a rare earth metal chelate-labeled probe, and a time-resolved fluorescence detection. The new assay system was evaluated for various reaction conditions including, DNA denaturation time, hybridization salt concentration, probe concentration, and hybridization time, all of which are important in designing an assay with a high level of sensitivity for the detection of duplex DNA. This nonisotopic assay system was applied to the detection of purified human immunodeficiency virus (HIV) DNA and sensitivity was compared with agarose gel electrophoresis and slot blot hybridization using a 32P-labeled probe. We were able to detect the amplified product from one copy of HIV DNA after 35 cycles of PCR amplification in less than 30 min using this assay, which compared with one copy by gel electrophoresis after 40 cycles of PCR amplification and one copy by slot blot hybridization after 35 cycles of PCR amplification and an overnight exposure of the autoradiogram. Thus, this assay is rapid, sensitive, and easy to use. PMID- 1621976 TI - HPLC analysis of free amino acids and amino acids of total proteins in cultured cells: an application to the study of rat Sertoli cell protein metabolism. AB - A simple, rapid and, sensitive HPLC method, coupled with fluorometric detection, has been worked out and employed to determine the intracellular free amino acid concentrations and the amino acid composition of total proteins in rat Sertoli cell primary culture. Sertoli cells were isolated enzymatically from testes of 20 and 28-day-old rats and cultured at 32 degrees C in Eagle's minimum essential medium. On the second day of culture, cell monolayers were quickly rinsed with ice-cold saline, immediately frozen in liquid nitrogen, accurately harvested, and homogenized in 10% trichloroacetic acid. Tissue free amino acids were determined in the acidic soluble fraction following neutralization, while the precipitate was hydrolyzed for the evaluation of the fractional content of amino acids into total proteins. Amino acid samples were derivatized with o-phthaldialdehyde/3 mercaptopropionic acid and resolved by a linear one-step acetonitrile gradient in 12.5 mM sodium phosphate buffer, pH 7.2, employing a 5-microns particle size reversed-phase column. Fluorescence was monitored with excitation at 330 nm and emission at 450 nm. Under these conditions all major physiological amino acids could be satisfactory separated, identified, and subsequently quantified with the aid of standards. The run time was about 50 min; the linearity was excellent over a large range of concentrations (1-800 pmol) and the lower limit of sensitivity appeared to be 0.5 pmol. This method permits us to demonstrate age-dependent modifications in the intracellular amino acid pool and to adequately evaluate the process of protein synthesis in cultured Sertoli cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1621977 TI - Recombination and amplification of multiple portions of genomic DNA by a modified polymerase chain reaction. AB - A novel method, a modified polymerase chain reaction (mPCR), is reported for in vitro recombination and amplification of two or more regions of DNA located in distinct parts of a genome such as exons of a gene. The reaction consists of three stages. In the first stage, the portions are amplified individually with the aid of four or more primers. Of the primers, two (outside primers) are complementary to 3'-terminal parts of the objective, recombinant DNA, and the others (inside primers) are complementary to 3'-terminal parts of the other portions. Some of the inside primers have extra nucleotide sequences at their 5' termini which are complementary to 5'-terminal parts of the portions to be recombined. In the second stage, the strands with complementary sequences in their 3'-terminal parts are annealed sequentially to one another and are converted to recombinant DNA with DNA polymerase. In the final stage, the objective DNA is amplified with the excess outside primers. The application of this method for in vitro recombination and amplification of three exons of the gene for human muscle-specific phosphoglycerate mutase is described. PMID- 1621978 TI - Solubilized substrates for the on-line measurement of lipases by flow injection analysis during chromatographic enzyme purification. AB - A flow injection analysis (FIA) system for the on-line measurement of lipases in chromatographic processes has been developed. The photometrically detectable substrates para-nitrophenylpalmitate, S,O,O'-tripropyryl-1-thioglycerol, and 1,2 O-dilauryl-rac-glycero-3-glutaric-resorufinester were investigated. Different detergents and qualities of assay emulsions were tested for optimal results in FIA applications. Emphasis was placed on increasing the stability of the assay emulsion. Lipases of different origin and specificity were detected. The linear detection range was adapted to the requirements of the chromatographic purification procedures. The connection of the FIA with a fast protein liquid chromatography system permitted the automatization of lipase purification by monitoring protein content, salinity, and enzyme activity of the effluent from column chromatography. PMID- 1621979 TI - Evaluation of a procedure for the simultaneous determination of oxidized and reduced pyridine nucleotides and adenylates in organic phenol extracts from mitochondria. AB - An extraction procedure using mixtures of phenol, chloroform, and isoamyl alcohol originally applied to quench mitochondria for determining adenylates proved suitable also for the quantification of reduced and oxidized pyridine nucleotides yielding recoveries of more than 90%. In combination with HPLC, this approach allows the simultaneous determination of NAD+, NADP+, NADH, and NADPH as well as of adenylates within one extract. A comparison of this extraction method with fluorimetric measurements of pyridine nucleotide reduction in intact mitochondria revealed that about 30% of the fluorescence signal in the resting state of liver mitochondria is caused by NADPH. PMID- 1621980 TI - Lectin-based homogeneous enzyme-linked binding assay for estimating the type and relative amount of carbohydrate within intact glycoproteins. AB - The feasibility of using a new lectin-based homogeneous enzyme-linked binding assay for estimating the type and relative amount of specific carbohydrate structures within intact glycoproteins is examined. Malate dehydrogenase galactose, -mannose, and -N-acetylglucosamine conjugates are utilized in conjunction with Jacalin, concanavalin A, and wheat germ agglutinin, respectively. The catalytic activity of the glyco-enzyme conjugates is inhibited significantly (greater than 60%) in solution in the presence of the respective lectins. The observed inhibition for each reagent set is reversed in proportion to the type and relative amount of specific carbohydrates present within test glycoproteins added to the assay mixture. Competitive binding ED50 values for a number of synthetic and native model glycoproteins correlate well with the known carbohydrate content of these species. The proposed method is much faster than previous solid-phase lectin-based enzyme-linked methods used to probe carbohydrate content/structure (less than 15 min) and has the potential to be fully automated. PMID- 1621981 TI - Polyisobutylmethacrylate modifies glycolipid binding specificity of verotoxin 1 in thin-layer chromatogram overlay procedures. AB - Verotoxins (or Shiga-like toxins) are a family of closely related toxins elaborated by Escherichia coli. At least three toxins have been described, VT1, VT2, and SLTII, in addition to Shiga toxin itself, and all bind to globotriaosyl ceramide, Gb3. Some discrepancies exist in the literature regarding the binding of the toxins to Gb4 as monitored by TLC overlay procedures. These procedures are widely used to investigate the specificity of carbohydrate-binding ligands. Polyisobutylmethacrylate, PIBM, is generally used in TLC overlay procedures to prevent silica loss and orient carbohydrate moieties for the binding of various ligands to glycolipids. We now report that pretreatment of chromatograms with PIBM modifies binding of VT1 to include Gb4 and decreases binding to Gb3 and the P1 glycolipid. We suggest that PIBM can alter the conformation of the glycolipid oligosaccharide, and therefore caution is advised in analysis of ligand binding to glycolipids after treatment with this compound. PMID- 1621982 TI - The 5'-terminal phosphates slow migration of single-stranded DNA fragments during electrophoresis in nondenaturing acrylamide gels. AB - Removal of the 5'-terminal phosphate results in an observable acceleration of the migration of single-stranded DNA fragments in the course of electrophoresis in nondenaturing acrylamide gels. This effect was observed with fragments 30-450 nucleotides in length. The relative difference in the migration of dephosphorylated and phosphorylated fragments depends on their length and primary structure and on the conditions of electrophoresis. The distinct mobility can advantageously be used to determine the level of terminal phosphorylation of DNA fragments during the work with phosphatases and polynucleotide kinases. PMID- 1621983 TI - Use of Marfey's reagent to quantitate racemization upon anchoring of amino acids to solid supports for peptide synthesis. AB - A chromatographic assay has been developed to quantitate racemization occurring during attachment of protected amino acids to peptide synthesis resins. Acidolytic cleavage of deprotected amino acids from supports and subsequent derivatization with 1-fluoro-2,4-dinitrophenyl-5-L-alanine amide (Marfey's reagent) gave diastereomers separable by reverse-phase HPLC using aqueous acetonitrile. The assay is reliable to 0.1% racemate with a detection limit of approximately 100 pmol. The technique was applied to several acid-labile resins and was used to evaluate the racemizing characteristics of various anchoring methods. PMID- 1621984 TI - Detection, isolation, and characterization of oligo/poly(sialic acid) and oligo/poly(deaminoneuraminic acid) units in glycoconjugates. AB - We have evaluated methods for separation, preparation, and characterization of alpha-2----8-linked oligomers of sialic acids (Neu5Ac and Neu5Gc) and deaminated neuraminic acid (KDN; 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid) recently found as a naturally occurring novel type of sialic acid analogue. (A) We examined preparative anion-exchange chromatography for fractionation and preparation of oligo(Neu5Ac), oligo(Neu5Gc), and oligo(KDN). (B) We also examined the TLC method for separation and differentiation of the partial acid hydrolysates of colominic acid, as well as polysialoglycoproteins (PSGP) and poly(KDN)-glycoproteins (KDN-gp) isolated from rainbow trout eggs, and for discrimination of lower oligomers of Neu5Ac, Neu5Gc, and KDN. (C) We developed the high-performance adsorption-partition chromatographic method for (a) separation of monomers and oligomers of three nonulosonates according to the difference in substituents at C-5 and the presence or absence of 9-O-acetyl groups in oligo(KDN) and (b) separation of three homologous series of lower oligomers according to the degree of polymerization. (D) We examined and compared high-performance anion-exchange chromatographic separation of 3H-labeled oligo(Neu5Ac), oligo(Neu5Gc), and oligo(KDN) alditols by using Mono-Q HR 5/5 resin. (E) We examined a method of selective and quantitative microprecipitation for separation and purification of oligomers and polymers of Neu5Ac by treating them with cetylpyridinium chloride. We also used PSGP and KDN-gp to test both the sensitivity and the selectivity of this method. PMID- 1621985 TI - Detection of catalytic monoclonal antibodies. AB - Several laboratories have now shown that monoclonal antibodies having enzyme-like properties can be generated. The generation of catalytic antibodies makes use of the same basic procedures that have been used for the generation of binding monoclonal antibodies, yet the process involves an additional crucial step: screening for catalytic activity. In this paper we address the unique problems involved in the detection of inefficient catalytic activity that is accompanied by uncatalyzed background reaction. An analysis that allows optimization of assay conditions and estimation of the minimal antibody concentration required to observe catalysis is presented. The results indicate that the structure of the substrate should be optimized to increase its affinity (i.e., decrease its Km) and reduce its concentration to pseudo-first-order conditions (S(O) much less than Km) so that the signal observed in the presence of a catalytic antibody (delta Pcat) is significantly higher than that of the background (delta P(uncat)). Other factors involved in the screening procedures, e.g., sensitivity of the assay, solubility and reactivity of the substrate, and purity of the antibody preparation, are also discussed. The effect of these assay parameters on the ability to detect catalytic activity is demonstrated with p-nitrophenyl ester hydrolyzing antibodies. PMID- 1621986 TI - A general method for preparation of peptides biotinylated at the carboxy terminus. AB - A method for the preparation of a biotinylated resin that can be elongated by standard methods of solid-phase peptide synthesis to give peptides biotinylated at the carboxy terminus is described. This methodology is particularly important for the preparation of biotinylated peptides in which a free amino terminus is required. Coupling of N epsilon-9-fluorenylmethoxycarbonyl-(Fmoc)-N alpha-tert butyloxycarbonyl(Boc)-L- lysine to p-methylbenzhydrylamine resin, followed by removal of the Fmoc protecting group and reaction with (+)-biotin-4-nitrophenyl ester yielded N alpha-Boc-biocytin-p-methyl-benzhydrylamine resin. The utility of this resin was tested by the synthesis of a biotinylated peptide, Gly-Asn-Ala-Ala Ala-Ala-Arg-Arg-biocytin-NH2, for use as an in vitro substrate for myristoyl CoA:protein N-myristoyltransferase (NMT), the enzyme that catalyzes protein N myristoylation. Analysis of the peptide derivative by HPLC and mass spectrometry revealed a single major product of the expected mass, indicating that the biotin group survived cleavage and deprotection with HF. The biotinylated peptide served as a substrate for NMT, and the resulting myristoylated peptide could be quantitatively recovered by adsorption to immobilized avidin. PMID- 1621987 TI - Characterization of human follicle-stimulating hormone binding to human granulosa cells by an immunoenzymological method. AB - An original, nonradiometric method has been developed for studying the binding parameters of native follicle-stimulating hormone (FSH) to its specific receptors in human ovarian granulosa cells. After binding and washing of the cells, hFSH was desorbed from its receptors and quantitatively measured by a specific enzyme immunoassay (EIA) in which nonspecific binding was estimated in the presence of an excess of equine chorionic gonadotropin (eCG/PMSG), which binds to human FSH receptors but does not interfere in the hFSH EIA. This method makes use of native nonmodified hFSH molecules (in contrast to radiometric methods) and permits direct estimation of the binding parameters (Kd and total number of sites). The Kd of hFSH for its human granulosa receptors measured by this technique (4.8 +/- 0.3 x 10(-10) M) is close to that determined by other methods. However, we found a total number of specific FSH receptors per granulosa cell (1 to 6 x 10(4) higher than that reported by others by Scatchard analysis of competition dose response curves in radioreceptor assays. The method is also sensitive enough to measure the in vivo occupancy of receptors by endogenous hFSH, which was found to be less than 6% in women undergoing hormonal treatment for in vitro fertilization. PMID- 1621988 TI - Detection of amplified HTLV-I/-II viral sequences using time-resolved fluorometry. AB - Since its discovery, the polymerase chain reaction (PCR) has been used for different purposes in the field of DNA research. We tested the PCR for the diagnosis of HTLV-I/-II infections. PCR was used to amplify 141- and 149-base pair regions from the HTLV-I and HTLV-II virus genomes, respectively. The annealing temperature in the PCR amplification was optimized using 20% polyacrylamide gels and silver staining. Even a slight change (3 degrees C) in the annealing temperature had an effect on the specificity of the reaction. The PCR products were detected with biotin and Eu-labeled oligonucleotide probes in a solution hybridization format. The linearity of the assay was tested with serial dilutions of purified chromosomal DNA containing integrated HTLV-II sequences. The linearity was found to be dependent on the number of cycles used in the PCR amplification. The best linearity, at a target level of a few copies, was achieved using a low number of cycles. The specificity of the assay was tested using HTLV-I and HTLV-II-infected lymphocytes from the cell lines Hut102 and MO480, respectively. No cross reactivity between these analytes was observed. PMID- 1621989 TI - Synthesis of (6S)-5-formyltetrahydropteroyl-polyglutamates and interconversion to other reduced pteroylpolyglutamate derivatives. AB - 5-Formyltetrahydropteroylpolyglutamates can be synthesized and purified directly from dihydropteroylpolyglutamates in a single-step procedure without purification of intermediates and with yields greater than 90%. The procedure involves a coupled enzymatic synthesis of 10-formyltetrahydropteroylpolyglutamates using the enzymes dihydrofolate reductase, serine hydroxymethyltransferase, and C1 tetrahydrofolate synthase with catalytic amounts of NADPH. The 10 formyltetrahydropteroylpolyglutamates are subsequently converted to 5 formyltetrahydropteroylpolyglutamates at 90 degrees C with near quantitative yields. 5-Formyltetrahydropteroylpolyglutamates are the only stable reduced derivatives of tetrahydropteroylpolyglutamates and can be purified and stored indefinitely without decomposition. Additionally, 5 formyltetrahydropteroylpolyglutamates can be readily converted to other derivatives of tetrahydropteroylpolyglutamates with yields greater than 95%. Also described is the synthesis of tetrahydropteroylglutamates labeled at C-11 with either 14C or 13C. Rapid purification procedures for serine hydroxymethyltransferase and C1-tetrahydrofolate synthase from frozen rabbit livers are presented. PMID- 1621990 TI - Extraction and isolation of mRNA from adult articular cartilage. AB - We have developed a method to isolate RNA in high yield from adult articular cartilage. Homogenization of the articular cartilage with a freezer mill, extraction with 4 M guanidinium isothiocyanate/acid-phenol, and ultracentrifugation in cesium trifluoroacetate was found to be an effective and practical method for isolating a high yield of intact RNA from adult canine articular cartilage. The total RNA was suitable for Northern blot analysis. The mRNA that could then be isolated by oligo-dT affinity chromatography was found to be a suitable substrate for in vitro translation, for making a cDNA library, and for PCR amplification. PMID- 1621991 TI - A transfer membrane method for in situ detection and quantification of trehalase. AB - A method for the detection and quantification of trehalase activity (EC 3.2.1.28) by immobilization to a membrane support has been developed. Protein samples partly enriched for porcine and Galleria mellonella wax moth larvae trehalase activities were fractionated by polyacrylamide gel electrophoresis, followed by electrophoretic transfer to PVDF membranes, and incubated in a solution containing trehalose (20 mg/ml), glucose oxidase (40 U/ml), phenazine methosulfate (0.06 mg/ml), and nitro blue tetrazolium (0.24 mg/ml) in 20 mM sodium phosphate buffer, pH 6.5. The intensity of the red-colored bands, developed directly on the membrane, was quantified using a computing, laser densitometer and shown to be linearly proportional to the original enzyme activity in extracts determined by liquid assay. The temperature inactivation profile of wax moth trehalase was measured. Alteration of the electrophoresis sample buffer composition further revealed the presence of putative trehalase isoforms in wax moth larval extracts whose relative levels of activity were altered during the course of starvation and infection with Tipula iridescent virus. PMID- 1621992 TI - Polymeric porogens used in the preparation of novel monodispersed macroporous polymeric separation media for high-performance liquid chromatography. AB - A novel approach to monosized macroporous polymeric separation media with vastly enhanced pore size distributions and chromatographic properties has been developed. Key to this approach is the combined use of monodispersed polymeric particles and suitable solvents as porogens in the copolymerization of styrene and divinylbenzene. Following polymerization, the polymeric porogen is dissolved, leaving behind the monosized beads with a controlled pore structure. The exact pore size and pore size distribution of the final beads are largely controlled by the amount of soluble polymer in the polymerizing mixture: the larger the proportion of soluble polymer in the system, the larger the pores. The uniformly sized macroporous beads prepared with an optimized ratio of polymeric and low molecular weight porogens proved to be very efficient even in short columns for the separation of polystyrene standards in the SEC mode and the separation of proteins in the reversed-phase mode. The relationship between pore size and specific surface area, on one hand, and chromatographic properties of the stationary phase, on the other, have been clearly documented. PMID- 1621993 TI - Electrochemical characteristics of amino acids and peptides derivatized with naphthalene-2,3-dicarboxaldehyde: pH effects and differences in oxidation potentials. AB - The electrochemical oxidations of the cyanobenz[f]isoindole (CBI) derivatives of 18 amino acids and 15 peptides, including enkephalins and several enkephalin fragments, were studied. Cyclic voltammetry indicated that the oxidation potentials of derivatized amino acids were virtually independent of pH. The utility of this pH-independence was demonstrated by controlling, through varying the pH, the selectivity with which CBI derivatives could be detected in the presence of phenolic compounds. In addition, hydrodynamic voltammograms of derivatized amino acids and peptides were constructed from chromatographic data and compared. The E1/2 values among the derivatized amino acids covered a range of 215 mV, with the derivatives of the basic amino acids being the easiest to oxidize and those of the acidic amino acids being the most difficult to oxidize. The E1/2 values of the derivatized peptides examined varied by 270 mV, with minor variations in structure capable of producing marked changes in oxidation potential. These results indicate that voltammetry can aid in identification or selective detection of CBI derivatives of amino acids or peptides. PMID- 1621994 TI - Evaluation of transient responses of ammonia-selective potentiometric electrodes for quantitative applications. AB - An error-compensating, predictive kinetic method is adapted and evaluated for quantitative applications based on transient responses from an ammonia-selective electrode. Transient data collected during the early part of the electrode response are used with a curve-fitting method and appropriate mathematical models to predict the signal that would be measured if the response were monitored to equilibrium. Several different theoretical and empirical models were evaluated, and all but one of the models tested permitted reliable prediction of equilibrium potentials for most responses. Predicted values of equilibrium signal were close to measured values and exhibited the expected logarithmic dependence on ammonia concentration in the range from 0.1 to 100 mmol/L. Slopes of calibration plots E infinity vs log C, varied from about 50.5 to 65.0 mV per decade with an average value of 56.9 +/- 4.2 mV per decade. Quantitative data are used to rank the different models in terms of their utility for kinetic-based determinations of ammonia by using the ammonia-selective electrode. PMID- 1621996 TI - Random breakage. PMID- 1621995 TI - Steric factors affecting the discrimination of isomeric and structurally related olefin gases and vapors with a reagent-coated surface acoustic wave sensor. AB - An investigation of steric factors affecting the olefin-olefin selectivity of a surface acoustic wave (SAW) sensor coated with reagents of the general formula trans-PtCl2(ethylene)-(substituted-pyridine) is described. Detection is based on the mass increase accompanying replacement of ethylene by other gas-phase olefins to form the corresponding olefin-substituted products. Selectivity depends on the relative reaction rates of the different olefins. Within series of structurally similar butenes, acrylates, and aromatic olefins, unusually high selectivity is observed for the less hindered olefins and complete discrimination of isomers is achieved in certain cases. Replacing pyridine by 2-methylpyridine and 2,6 dimethylpyridine in the reagent complex progressively reduces the sensor response. Sensitivities increase with increasing temperature and limits of detection ranging from about 2 to 70 micrograms/L are achieved with modest heating (30-40 degrees C) using a 30-MHz SAW oscillator. Initial results with a 52-MHz sensor shows a 3.4-fold increase in sensitivity compared to the 30-MHz sensor in rough agreement with theory. PMID- 1621997 TI - Collisionally induced dissociation in the study of A-ring hydroxylated vitamin D type compounds. AB - Collisionally induced dissociation (CID) is often used to determine the structure of ions based on comparison with the CID spectra of known ions. The latter are generated from judiciously selected compounds taking into account basic principles of ion chemistry. We report here on the use of this approach toward determination of the site of A-ring hydroxylation of vitamin D. Although not intrinsically an aromatic compound, vitamin D gives rise in its mass spectrum to an aromatic methylstyryl cation at m/z 118. A-ring hydroxylated metabolites of vitamin D would thus incorporate the extra OH group on the ion at m/z 118, shifting it to m/z 134. The position of substitution of the extra OH group on a metabolite could then be ascertained by comparing the CID spectrum of its m/z 134 fragment to those of the four possible (hydroxymethyl)styryl cations generated from synthesized authentic compounds. Because of their propensity to polymerize, these cations were generated in situ via the McLafferty rearrangement of the corresponding (hydroxyphenyl)ethanols. For optimum differentiation of isomeric ions, preparation of permethylated derivatives of vitamin D was necessary. The validity of the hypothesis was verified using 1,25-dihydroxy-vitamin D3 as a test compound. This method provides a viable approach for the characterization of A ring hydroxylated metabolites of vitamin D as well as for related aromatic compounds. PMID- 1621998 TI - Supercritical carbon dioxide extraction of 2,4-dichlorophenol from food crop tissues. AB - Supercritical fluid extraction with carbon dioxide has been found to be effective for the isolation of residue levels (0.1-1 ppm) of 2,4-dichlorophenol from selected plant tissues. The 2,4-dichlorophenol residues were incompletely extracted with supercritical CO2 alone, since a substantial fraction of the 2,4 dichlorophenol was covalently attached to the plant matrix. An acid pretreatment procedure was developed to partially hydrolyze the plant tissue prior to extraction, releasing the bound 2,4-dichlorophenol residues. Steam distillation showed higher residue levels for field-treated straw samples. This is attributed to the greater degree of hydrolysis inherent in the steam distillation procedure. Supercritical CO2 extraction of field-treated seed samples showed higher levels of 2,4-dichlorophenol residues than did steam distillation. The supercritical fluid extractant was able to solvate 2,4-dichlorophenol residues in the interior of the seed and transport them to the surface for collection. The aqueous medium used in steam distillation was unable to penetrate the hydrophobic seed matrix to the same degree. While the actual extraction time experienced in supercritical fluid extraction was far less than that of steam distillation (45 min vs 6 h, respectively), the total sample preparation time was similar in both methods. PMID- 1622000 TI - Development of an eluotropic series for the chromatography of Lewis bases on zirconium oxide. AB - Ligand-exchange interactions, which dominate the retention characteristics of Lewis base solutes on zirconium oxide, can be strongly attenuated by the addition of a competing Lewis base to the eluent. The chromatographic effects of these competing bases vary significantly in their thermodynamics and kinetics depending on their structure and Lewis basicity. An eluotropic scale of mobile-phase strength for ligand-exchange/ion-exchange chromatography on zirconia has been developed which ranks the overall elution strength of a variety of Lewis bases in terms of their ability to elute a wide variety of benzoic acid derivatives. This series generally holds true for similar solutes; however, deviations are noted with some solutes and eluents where chelation and steric factors alter the kinetic and thermodynamic characteristics of the retention process. PMID- 1621999 TI - The role of Lewis acid-base processes in ligand-exchange chromatography of benzoic acid derivatives on zirconium oxide. AB - Porous microparticulate zirconium oxide shows very different selectivities and pH dependencies for the separation of benzoic acid derivatives than do conventional bonded-phase anion-exchange supports. This results from a very significant ligand exchange contribution to the retention of hard Lewis bases on the surface of transition-metal oxide supports. We have found that the capacity factors of a wide variety of derivatives of benzoic acid are closely correlated with their Bronsted acidities. The eluent pH is also a critical factor in determining the magnitude of the capacity factor, but it does not have much influence on chromatographic selectivity. The differential selectivity of this phase in comparison to conventional polymeric and bonded-phase anion exchangers can be attributed to complexation and steric effects which profoundly alter the elution patterns of certain solutes. PMID- 1622001 TI - Peptide mapping of complex proteins at the low-picomole level with capillary electrophoretic separations. AB - A variety of different peptide-mapping schemes are presented, with emphasis on the development of procedures which can be done with limited quantities (i.e. 5 pmol) of protein. Results are obtained from model proteins which contain disulfide bonds, which must be broken prior to fragmentation of the protein. A reaction involving the simultaneous use of tributylphosphine and 2 methylaziridine to reduce and alkylate the disulfide bonds is employed, due to favorable attributes of these reagents for the scaled-down procedure. The traditional performic acid oxidation reaction to cleave cystine groups is also successfully used with low-picomole quantities of protein. Three different protein digestion reagents are used: trypsin, chymotrypsin, and cyanogen bromide. Each reagent produces a unique mixture of peptides. Capillary electrophoresis is used to separate the peptides, offering high separation efficiencies, short analysis times, and compatibility with small sample sizes. In addition to the conventional use of UV detection for underivatized peptides, laser-induced fluorescence detection is employed in conjunction with an arginine-selective derivatization reaction. This latter procedure for derivatization and detection offers an alternative peptide-mapping mode, in which only the arginine-containing peptides are detected, and is useful in simplifying the peptide maps of large proteins. PMID- 1622002 TI - Hartley/Hilbert transform spectroscopy: absorption-mode resolution with magnitude mode precision. AB - Fourier transformation (FT) of an N-point time-domain discrete signal produces, after phase correction, two independent data sets: an N/2-point absorption spectrum, A(omega), and an N/2-point dispersion spectrum, D(omega), each with the same information content. Usually only A(omega) is kept. The dispersion-mode information has conventionally been recovered in either of two ways. First, the N/2-point magnitude-mode spectrum, M(omega) = ([A(omega)]2 + [D(omega)]2)1/2, offers a square root of 2 improvement in precision compared with the original N/2 point absorption spectrum, but with poorer resolving power (factor ranging from square root of 3 to 2 for unapodized data). Alternatively, zero-filling the initial time-domain data to 2N data points prior to Fourier transformation results in an N-point absorption-mode spectrum with the same peak width and peak height-to-noise ratio as the original N/2-point absorption spectrum, but with a square root of 2 improvement in precision. Thus, magnitude-mode display improves FT spectral precision at the expense of a loss in resolving power, whereas zero filling improves precision at the expense of having to store twice as many data points. In this paper, we present a third method of recovering the dispersion information.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1622003 TI - Tandem mass spectrometric analysis of peptides at the femtomole level. AB - In the sequential analysis of peptides by fast atom bombardment (FAB) tandem mass spectrometry (MS/MS), the principal obstacle to decreasing sample quantities was determined to be the signal-to-background ratio of the ionization/desorption process. By decreasing the background ion current, continuous-flow FAB allows complete analysis (both MS and MS/MS) to be performed on 25-75% less sample than required for a conventional FABMS/MS experiment alone. The combination of CF-FAB with array detection permitted sequential analysis of several peptides (900-2000 Da) at the 900 fmol to 5.8 pmol level, without interference from the background. These levels do not produce a molecular ion species easily discernible above the background in conventional FAB. PMID- 1622004 TI - Raman spectrometry with metal vapor filters. PMID- 1622005 TI - Sensitive, laser-assisted determination of complex oligosaccharide mixtures separated by capillary gel electrophoresis at high resolution. PMID- 1622006 TI - Technique for packing the perineal wound after a wide perineal dissection for adenocarcinoma of the rectum. AB - A technique for packing the perineal wound after a wide perineal dissection performed as part of an abdominoperineal resection is described. An isolation bag is filled with rolled gauze and positioned in the pelvis beneath the sacral promontory. The packing and the bag are removed on the fifth postoperative day. This technique is safe and more tolerable to patients with an open perineal wound after an abdominoperineal resection. PMID- 1622007 TI - Selective versus routine antibiotic use in acute appendicitis. AB - Whether prophylactic antibiotics should be employed routinely in all patients with presumed appendicitis rather than be administered selectively to those with suspected perforation remains a controversial issue. The outcome of 312 adult patients undergoing appendectomy during periods of selective (I, n = 153) and routine (II, n = 159) antibiotic use were compared. Although the rates of misdiagnosis were comparable (9% vs 13%), significantly more patients with appendicitis in Period II had perforated appendicitis (29 of 139 vs 44 of 139, P less than 0.05). Prophylactic antibiotics were given to 43 (28%) patients in Period I compared to 132 (83%) in Period II (P less than 0.001). This, increased frequency was true for both simple (21% vs 81%, P less than 0.001) and perforated (66% vs 86%, P less than 0.05) appendicitis. A single antibiotic, most frequently a cephalosporin, was used significantly more often in Period II (44% vs 82%, P less than 0.001). There was no significant difference in the methods of wound closure between the two periods. The incidence of infectious complications was similar in patients with simple appendicitis in both periods (8% vs 11%), but it was significantly greater during Period I in patients with perforated appendicitis (45% vs 20%, P less than 0.05). The overall infection rate was similar in both periods (16% vs 22%). Thus, high-risk patients with perforated appendicitis were more likely to receive antibiotics and had a lower infection rate with routine antibiotic use. Furthermore, there was no overall change in the infection rate during this period, despite the use of less toxic, single drug regimens and a greater percentage of perforated appendicitis. PMID- 1622008 TI - Gangrenous cholecystitis: five patients with intestinal obstruction. AB - Gangrenous cholecystitis, a disease more common in older patients and diabetics, may be complicated by perforation, pericholecystic abscess, and fistula. Intestinal obstruction has rarely been reported as a complication and only in cases involving perforation or acute, nongangrenous cholecystitis. A retrospective review of hospital records between 1961 and 1989 identified 126 patients with gangrenous cholecystitis, five of whom came to the hospital with intestinal obstruction. Three were cases of paralytic ileus and two of simple mechanical obstruction without perforation. The latter group may represent the first such cases reported. Gallbladder perforation occurred in two patients and cholelithiasis was found in three. The mean age of the total patient cohort was 70.6 years; patients were predominantly male and black. Hypertension and diabetes were common concomitant diseases. Patients commonly came to the hospital with nausea and vomiting, increasing abdominal girth, and obstipation. A leukocytosis on admission was more common than fever or hyperbilirubinemia. The clinical presentation of intestinal obstruction and the lack of objective data specific for gangrenous cholecystitis made a preoperative diagnosis impossible. Thus, a high index of suspicion should increase diagnostic accuracy. The incidence of intestinal obstruction (at presentation) in cases of gangrenous gallbladders was 4 per cent. Morbidity and mortality are reduced with early operation. PMID- 1622009 TI - Perforated ulcers related to smoking "crack" cocaine. AB - This article describes four patients with perforated gastroduodenal ulcers related to smoking "crack" cocaine. All patients came to the hospital with acute abdominal pain; only one patient had a history of ulcer disease. Only one patient had an elevated white blood cell count, and two patients had depressed white blood cell counts. In three patients, the x ray showed that pneumoperitoneum was present. Upon surgical exploration of the abdomen, all patients were found to have extensive peritoneal contamination. Operative repair consisted of omental patching with or without primary closure of the perforation. A history of cocaine smoking should be sought in patients with unexplained abdominal pain or pneumoperitoneum. In patients with acute abdominal pain and a history of smoking cocaine, a perforated gastroduodenal ulcer may be present, despite normal or low white blood cell counts and the lack of pneumoperitoneum on x-ray examination. PMID- 1622010 TI - Subtotal colectomy as a last resort for unrelenting, unlocalized, lower gastrointestinal hemorrhage: experience with 12 cases. AB - A 7-year experience involving 12 cases of massive, unrelenting lower gastrointestinal hemorrhage is presented. In these patients, the bleeding could not be localized by multiple diagnostic modalities and was managed by blind subtotal colectomy. While the procedure was efficacious in arresting bleeding in all cases, a resultant mortality of four cases (33%) ensued. Morbidity among the survivors was significant. Only three patients (25%) survived without complications, which enabled an early discharge from the hospital. Diverticulosis was the most common cause (83%) of uncontrollable and preoperatively undiagnosed bleeding in this group of patients. These 12 cases of blind subtotal colectomy for massive lower gastrointestinal bleeding represent one of the larger series in the literature. These data are consistent with more recent reports that indicate that subtotal colectomy for lower gastrointestinal bleeding is an effective but a formidable procedure. This is contrary to the earlier published results. PMID- 1622012 TI - Absence of intestinal bile promotes bacterial translocation. AB - Previously, the authors documented that extrahepatic biliary obstruction promotes the systemic translocation of bacteria from the intestine to visceral tissues. The current experiments were performed to determine whether it was the absence of intestinal bile or the presence of biliary obstruction that promoted bacterial translocation. Four groups of rats were studied: 1) nonoperated controls (n = 20), sham common bile duct-ligated (n = 22), common bile duct-ligated (n = 25), and common bile duct-diverted (choledochovesical bypass) (n = 23). The sham ligated group underwent laparotomy and manipulation of the portal region; whereas the ligated group had their common bile ducts ligated, while the choledochovesical group had a silastic tube placed from the common bile duct to the bladder. Seven days later, at death, the incidence of bacterial translocation was higher in the groups of rats subjected to common bile duct ligation (41%) or diversion (32%) than in the control (3%) or sham-ligated (5%) groups (P less than 0.05). Histologic sections of ileums of ligated and diverted animals both showed subepithelial edema. These findings suggest that it is primarily the absence of bile in the intestine that promotes mucosal injury and bacterial translocation and not biliary obstruction. PMID- 1622011 TI - Management of benign, giant gastric ulcers. AB - Giant gastric ulcers (greater than 3 cm in diameter) have traditionally been considered to be refractory to medical therapy and were commonly thought to initially appear as life-threatening hemorrhage requiring emergent operative therapy. This study was undertaken to evaluate the results of medical and surgical treatment of benign, giant gastric ulcers and the validity of these traditional teachings. A retrospective review of 44 patients with giant gastric ulcers was performed to evaluate the results of medical and surgical therapy at Hartford Hospital (Hartford, CT). The majority of these patients received medical therapy. Over 57 per cent received only medical therapy, while 25 per cent received primary, operative therapy. Contrary to popular belief, the authors found that patients who received initial medical therapy did not have high morbidity or mortality rates. Therefore, while the necessity of early surgical intervention following perforation or in patients with signs of hemorrhagic shock can not be refuted, the authors conclude that medical therapy of benign, giant gastric ulcers is often effective and not unduly hazardous. Giant gastric ulcers, in and of themselves, are not an indication for surgery. PMID- 1622013 TI - Leiomyosarcoma of the rectum. AB - Leiomyosarcoma of the rectum is a rare entity. Approximately 150 cases have been described in the literature. Differentiation from its benign counterpart, leiomyoma, and other connective-tissue tumors is often difficult, but it is important because each tumor has an entirely different prognosis. The case of a patient in whom an 11 x 5.5 cm leiomyosarcoma of the rectum was surgically excised by abdominoperineal resection is presented. Literature review shows disagreement over the therapeutic approach, most likely due to the lack of a large series of patients with this disease. At present, a selective treatment approach appears to be the most advocated. Lesions less than 2.5 cm in size and limited to the bowel wall can still be treated by wide local excision. More radical surgical resection is indicated for larger tumors and those extending outside the bowel wall. PMID- 1622014 TI - Contemporary management of amebic liver abscess. AB - In a retrospective review covering 16 years divided into two time periods, 133 patients with amebic liver abscess were evaluated. Most of the patients were young, Hispanic men, and one-third had coexistent disease. A reliable diagnosis can be established in 24 hours using ultrasound or computed tomography scans. Over the entire time period, antiparasitic therapy was evolved to occupy a primary role and surgery was reserved for management of abscess complications. PMID- 1622015 TI - Changes in biliary bacteria after endoscopic cholangiography and sphincterotomy. AB - This prospective study consisted of 32 patients. In each patient, bile was collected during two separate endoscopic retrograde cholangiopancreatographies (ERCP) to study changes in biliary bacteriology and cytology. The mean interval between ERCPs was 20 months (15-29 months). Twenty-three patients had gallstones in the gallbladder, bile ducts, or both. Nineteen of them had bactibilia compared to none of the 9 patients with normal ERCP (P less than 0.001). Fifteen patients had normal bile ducts in ERCP (Group 1). Four of these patients (27%) had bactibilia initially and 9 (60%) at follow-up (P = 0.069). Seventeen patients had bile duct stones and underwent endoscopic sphincterotomy (Group II). Fifteen of these patients (88%) had bactibilia initially, and 15 (88%) also had bactibilia at follow-up. Initially, anaerobic bacteria were detected in 37 per cent of Group I patients with bactibilia and in 50 per cent of Group II patients with bactibilia. At follow-up, the bile in Group I patients infrequently (11%) contained anaerobes, whereas in Group II patients anaerobes predominated (67%; P less than 0.011). Clear correlation between the biliary cytology and bacteriology could not be observed. The authors conclude that ERCP may result in increased incidence of long-term bactibilia and suggest that contamination occurred during ERCP. The bactibilia associated with bile duct stones does not subside after endoscopic treatment of the common duct stones. PMID- 1622016 TI - Noncompression unicortical miniplate osteosynthesis of mandibular fractures. AB - The use of transoral noncompression unicortical miniplates in treating 42 consecutive patients with 64 displaced mandibular fractures (excluding subcondylar) was reviewed. Titanium miniplates (Wurzburg) were used for fixation. The principles set forth by Champy and colleagues, with two plates for body and symphyseal fracture fixation and one plate superiorly along the oblique ridge for angle fractures, were performed. Intermaxillary fixation was not used postoperatively. Results compared favorably with other forms of treatment with no evidence of postoperative malocclusion, with an overall complication rate of 3%. The advantage of no external incision, avoidance of intermaxillary fixation, and normal postoperative incisal opening and occlusion make this technique our treatment of choice. PMID- 1622017 TI - Thyroid disorders masquerading as aging changes. AB - Some (2.6%) patients seeking aesthetic blepharoplasty had undiagnosed hypothyroidism contributing to periorbital aging changes; 0.3% had undiagnosed hyperthyroidism. Characteristic features suggesting the possibility of hypothyroidism were edema, "festoons," and "secondary" bags. The characteristic features of hyperthyroidism were proptosis and edema. Treatment of the underlying medical condition reversed the changes to a variable extent. Aesthetic surgery was not necessary in some patients. PMID- 1622018 TI - Rhinoplasty and facial expression. AB - Based on the philosophical concept that facial beauty is not merely harmony of static anatomical structures but also the dynamic expression of the face (especially when one smiles), I propose that plastic surgeons approach the problem of aesthetic improvement of the human face not only in response but also when the face moves. I call this "surgery of the facial expression." I describe here the use of a new surgical procedure to correct a certain condition with which plastic surgeons are frequently confronted when patients consult and request rhinoplasty. Many patients have added defects that are exposed only when they begin to make facial movements and gestures; moreover, these added defects become even more manifest when they smile. I call this phenomenon "rhino gingivolabial syndrome of the smile," and describe the technique I have used not only to improve the form of the nose but also to enhance the patient's smile. PMID- 1622019 TI - Total lower lip reconstruction in advanced squamous carcinoma: application of the gate-flap technique. AB - During the years 1986 to 1988, seven patients with advanced squamous cancer of the lower lip were operated on in our department and the defects were reconstructed by the gate-flap technique. We found that this method affords satisfactory total reconstruction of the lower lip. Better results may be obtained if more attention is given to details such as the thickness of the pedicles, the opening of Stensen's duct, and advancement of the mucosa to form the vermilion. Late distortion due to scar contracture can be corrected by defatting and W plasty. PMID- 1622020 TI - Panniculus morbidus. AB - Eight patients with large panniculi are described where severe problems with hygiene, immobility, and chronic infection were caused by the lymphedematous, chronically infected pannus. Protracted nonsurgical management of the infected panniculus had failed in all 8 patients. Wedge resection without fat undermining removed diseased tissue. Infection and sepsis were eliminated and ambulation was restored in all patients. Formerly immobile patients were returned to normal activity. Significant self-induced weight loss was not observed in a 2-year follow-up period; weight gain, however, was not experienced. The primary anesthetic method was thoracic epidural reducing the requirements for general endotracheal anesthesia. The chronically infected pannus is a surgical problem deserving earlier recognition and resection. PMID- 1622021 TI - Experience with novel uses of tissue expanders in burn reconstruction of the face and neck. AB - Total or subtotal resurfacing of the face with suitable, well-matched skin from the upper trunk and neck is usually difficult because of the dearth of unscarred donor site. Tissue expanders have been used primarily to construct local advancement flaps of tissue immediately adjacent to a tissue defect or deformity. These flaps often lack adequate mobility to allow coverage of large areas. In this report, I describe a clinical experience of 11 patients followed for 27 to 75 months in whom tissue expanders were used to develop large, full-thickness skin grafts or transposition flaps for total or subtotal resurfacing of the face and neck. Large, full-thickness skin grafts were developed from relatively small donor sites using tissue expanders. They behaved identically to unexpanded full thickness skin grafts. They were found not to shrink with storage. The donor sites were closed primarily, obviating the need to graft the donor site. The tissue expander-enhanced transposition flaps appeared to have enhanced vascularity and provided ample, suitable tissue for reconstruction of the face and neck. Tissue expansion resulted in very mobile, thin, hearty flaps that provided excellently matched skin cover for the face and neck. Complications, some of which are unique to these techniques, and indications for the techniques are reviewed. PMID- 1622022 TI - Two devastating complications of carpal tunnel surgery. AB - Two devastating complications of carpal tunnel release are presented. In 1 patient, the median nerve was completely transected; in another, massive necrosis of the palm required free flap coverage. PMID- 1622023 TI - Plantar fibromatosis and bilateral flexion contractures: a review of the literature. AB - Plantar fibromatosis is a benign multinodular lesion occurring in the plantar fascia. It is generally an asymptomatic lesion or may occasionally cause discomfort or pain in the foot. We present a man who has bilateral flexion contractures of his great toes as a result of his plantar fibromatosis. A review of the literature indicates that this is a very rare presentation of plantar fibromatosis. PMID- 1622024 TI - Subdermal liposuction to enhance skin contraction: a preliminary report. PMID- 1622025 TI - Nipple-areola reconstruction with a custom-made silicone ectoprosthesis. AB - The use of a custom-made silicone ectoprosthesis of the nipple-areola complex is presented. It is suggested, after completion of breast mound reconstruction, for those women who cannot undergo or refuse to undergo any further surgical procedure, or else for the interim until the final reconstruction is performed. It is convenient to use and the aesthetic appearance is pleasing. PMID- 1622026 TI - Temporary tarsorrhaphy "zipper". AB - Reconstructive eyelid procedures on occasion justify the concomitant use of a temporary, reversible tarsorrhaphy to provide corneal protection. A dilemma ensues in the trauma patient when frequent neurological evaluations simultaneously requires examination of the pupils. To circumvent the inconvenience of repeated suturing of the eyelids as in an occlusive suture, a technique with the facility of the opening and closing of a zipper is reviewed that allows rapid removal and reestablishment of the desired temporary tarsorrhaphy. PMID- 1622027 TI - Silicone breast implants and immune disease. AB - Silicone was originally regarded as inert in the human body. Silicone medical devices have been associated with various complications that may involve an immune reaction to silicone or a silicone organic complex. There have been more than 80 cases reported in the medical literature of a varied systemic autoimmune illness in patients who have had various foreign materials placed in the breast. Controversy exists as to which complications have a cause and effect relationship, and which represent coincidental findings. It is difficult to distinguish between nonspecific local reactions and reactions that have an immunological basis. Approximately 1,000,000 to 2,000,000 women in the United States have had silicone breast implants inserted for reconstruction or augmentation mammaplasty; 28 of those patients have been reported to have developed a systemic autoimmune disease. Data on the 28 reported cases do not in any way prove a causal relationship between breast implants and immune disease. Given the natural incidence of autoimmune diseases, we would expect a coincidental occurrence in the United States of more than 1,000 cases of autoimmune disease in women who had undergone breast implant surgery. Additional information must be obtained to resolve the question. The true incidence of autoimmune disease in patients with implants needs to be determined. A prospective registry of implant patients should be established and comprehensive retrospective information obtained on the implant patient population. Further experimental work is necessary on the bioreactivity of silicone. Patients with implants and autoimmune disease, once identified, must be carefully evaluated by physicians who are experienced in the treatment of autoimmune disease. PMID- 1622028 TI - Re: Firestorm fibrosis: the fast fibrotic phenomenon. PMID- 1622029 TI - Re: Buccal fat pad excision: aesthetic improvement of the midface. PMID- 1622030 TI - The role of cutaneous lymphoscintigraphy in determining regional lymph node drainage of truncal melanomas. AB - In the absence of clinically positive regional nodes, any value of prophylactic dissection in malignant melanomas depends on accurate preoperative determination of the pathway of lymphatic drainage. We report on the use of noninvasive radionuclide lymphoscintigraphy in the determination of regional patterns of lymph node drainage in patients with melanomas. Ten patients were studied; treatment was altered by test results in 2. Eleven node groups were excised in 7 patients. There have been no metastatic melanomas found in any nodal basins not detected by lymphoscintigraphy 23 to 42 months after operation. PMID- 1622031 TI - Muscle flap monitoring in a rat model with a variable gain quantitative fluorometer. AB - A variable gain dermofluorometer with a wide range of sensitivities capable of quantifying fluorescein emission from both skin and muscle was tested in a rat latissimus dorsi island muscle flap model. Quantitative fluorometric readings directly from muscle and skin sites that did not undergo surgery were taken at intervals over 2 hours after intravenous fluorescein injection. Muscle flaps with intact pedicles gave an inflow-outflow pattern. A no-outflow pattern was seen in muscle flaps with ligated pedicle veins and a no-inflow pattern was seen in muscle flaps with ligated pedicle arteries. These patterns were similar to the flow pattern seen with quantitative fluorometric monitoring in flaps with cutaneous components. These results suggest that quantitative fluorometry may be applicable to circulation monitoring in muscle flaps. PMID- 1622032 TI - Elliptical breast reconstruction: an improved and simplified technique. AB - An improved and simplified postmastectomy reconstruction by tissue expansion is presented. Utilizing a uniquely designed matched tissue expander and prosthesis, the technique is based on an elliptical concept of breast shape and corresponding volumetric relationships and permits controlled expansion of the lower chest skin. Horizontal and vertical base dimensions and the volume of the contralateral breast are used to determine the size and volume of the appropriate elliptically shaped tissue expander and, subsequently, of the mammary implant. This approach permits surgeons to achieve symmetry more readily by matching the implant to the patient, rather than the patient to the implant. PMID- 1622033 TI - Ciprostene and indomethacin partially reverse the mechanisms of distal end necrosis in the rat random skin flap. AB - Survival of random skin flap distal end depends on hemodynamic, cellular, and coagulation mechanisms. This study was designed to evaluate whether administration of ciprostene, a stable prostaglandin I2 analogue, and indomethacin, a cyclooxygenase-hydroperoxydase enzyme inhibitor, would improve the survival rate of random skin flaps. Forty-five male rats were divided into nine groups and injected with sesame oil (control), ciprostene (20 micrograms/kg/day), and/or indomethacin (2 mg/kg/day). Injections were done before (pretreatment for 4 days), after (posttreatment for 6 days), and before/after (pre/posttreatment for 4 and 6 days, respectively) the elevation of random dorsal skin flaps. In the pretreatment and pre/posttreatment studies, the flap survival rate of all drug-injected groups was significantly higher than that of the control group (p less than 0.02). In addition administration of ciprostene alone yielded a trend of better flap survival rate, which, however, was not statistically significant (p less than 0.12). Of interest in the posttreatment study, only the simultaneous administration of ciprostene and indomethacin significantly increased skin flap viability compared with the other groups (p less than 0.02). Therefore, the results demonstrated that administration of ciprostene and indomethacin either alone or together partially reversed the pathophysiological mechanisms that cause necrosis of random skin flap distal end. These pharmacological changes significantly improved random skin flap survival rate. PMID- 1622034 TI - Macrophage interleukin 1 response to injected silicone in a rat model. AB - Observations of silicone granuloma formation and migration of silicone to regional lymph nodes have indicated a need for more research into the possible immunological responses to silicone. The present study was undertaken to assess the effect of injected silicone particles on the ability of splenic macrophages to produce interleukin 1 (IL-1) and to determine the relative quantities produced. Lewis rats were divided into 4 groups: Group 1 animals (n = 3) were injected subcutaneously with sterile saline (2.5 ml) and served as control animals; Group 2 animals (n = 3) also served as control subjects, but macrophages isolated from these animals were exposed to lipopolysaccharide (LPS); Group 3 animals (n = 3) were injected subcutaneously with Freund's complete adjuvant (FCA) (2.5 ml) to serve as FCA control animals; and Group 4 animals (n = 3) received a subcutaneous injection of a sonicated slurry of equal parts FCA and silicone (2.5 ml each). IL-1 production was not significantly increased in splenic macrophages from animals exposed to the silicone slurry (p greater than 0.20) 8 months after injection as compared with control animals or animals given FCA alone. Macrophages exposed to LPS, a known mitogen, had significantly elevated IL-1 production. Subcutaneously injected silicone particles did not elicit an increase in IL-1 production in rat macrophages. PMID- 1622035 TI - Strain differences in autotomy in rats undergoing sciatic nerve transection or repair. AB - The degree of self-mutilation (autotomy) following sciatic nerve injury was assessed in 6 rat strains. Experimental groups included sciatic nerve transection with and without repair and crush lesions. The degree of autotomy was measured using a standard grading system. There were statistically significant differences between the strains in the transected group in terms of both degree of autotomy and the time of onset of its appearance. The repair group showed a shorter mean time of onset, lower maximal scores, and lower percentage of affected animals. Autotomy was absent in the nerve crush group and in all Lewis rats. In experimental studies when the status of the foot is critical (e.g., to evaluate functional walking patterns) Lewis rats appear to be the most appropriate strain to utilize. These results suggest that there are definite strain differences in the degree of autotomy following nerve transection or repair. PMID- 1622036 TI - Evaluation of failed sphincter pharyngoplasties. AB - A review of 30 failed sphincter pharyngoplasties is presented. Failure may be caused by inappropriate surgical planning, inadequate surgical technique, or inappropriate patient selection. Problems with surgical planning and technique that lead to failure were low flap placement, flap dehiscence, and flaps not approximated in midline. Problems with patient selection that lead to failure were large velopharyngeal gap on videofluoroscopy, and residual speech (articulation) deficits. Careful pre- and postoperative evaluation has led to refinement of the surgical procedure and improved outcome. Success rate improved from 67.65% in the first 5 years to 86% in the last 5 years of this 15-year series. PMID- 1622037 TI - Hand rejuvenescence by fat filling. AB - The advantages of fat filling for hand rejuvenescence are discussed. Seventy-two patients treated by this method are presented, including their follow-up, complication rate, and details of combined operations. Preference is given to local anesthesia when no other major surgeries are associated with the method. A highly satisfactory rate was obtained (98.62%) with a low complication rate (4.15%). PMID- 1622038 TI - Free ascending scapular flap. AB - Four patients with free tissue transfer using ascending cutaneous branches of circumflex scapular vessels are herein presented. The free ascending scapular flap is located on the superior vertical axis, differentiated with the scapular flap horizontally and the parascapular flap vertically designed. The flap is an excellent choice because of easy dissection, a constant artery and venous system, 2- to 3-mm-diameter vessels, and sufficient length of the vascular pedicle. All flaps survived completely with a fairly thin skin. The shoulder donor site could be closed primarily. No functional deficit of the shoulder was observed. PMID- 1622039 TI - Management of traumatic supraorbital neuroma. AB - Traumatic neuromas represent proliferative overgrowth of axons, Schwann cells, and fibroblasts at the proximal end of nerve injury or transsection. Although common elsewhere, traumatic neuromas have rarely been noted in the orbits. All but one of these reported lesions occurred after orbital surgery. We present a patient with a painful traumatic neuroma of the supraorbital nerve due to application of a halo fixation device. Neuroma resection and microneural repair resulted in prompt resolution of symptoms without compromise of nerve function. PMID- 1622040 TI - Embolization in high-flow arteriovenous malformations of the face. AB - Five patients with arteriovenous malformations of the face (4 males and 1 woman; age range, 11-38 years) were treated by selective embolization through the feeding arteries with polyvinyl alcohol particles. Immediate gross angiographical obliteration was obtained in 4 patients, with pronounced reduction of the arteriovenous shunt in the fifth. Clinical symptoms including bleeding, swelling, pulsations, bruit, and disfigurement improved in all the patients followed up for a period of 6 to 21 months. Polyvinyl alcohol particle embolization, without surgical resection, though palliative could be useful in select patients. The classification and diagnosis of congenital vascular malformations is briefly reviewed and treatment discussed. PMID- 1622041 TI - Reconstruction of children's scalp defects with the Orticochea flap. AB - From January 1985 to February 1990, 4 children with scalp defects were selected for use of the Orticochea flap technique for reconstruction. The ages ranged from 15 months (the youngest in the literature) to 7 years. The defects ranged from 6 x 7 to 11 x 13 cm. Three defects were traumatic and 1 was acute lymphocytic leukemia septic emboli in cause. All these children got satisfactory results with follow-up periods ranging from 5 months to more than 5 years. With these preliminary experiences, we have verified that the Orticochea flap scalp reconstruction surgery described 20 years ago can be performed safely even in children, especially when tissue expansion is not suitable or readily available. PMID- 1622042 TI - Re: Which dressing for split-thickness skin graft donor sites? PMID- 1622043 TI - Re: Traumatic hemipelvectomy. PMID- 1622044 TI - Re: Plastic surgery endeavors in Estonia. PMID- 1622045 TI - Haemostatic responses to desmopressin acetate after primary coronary artery bypass surgery. AB - Previous studies have suggested that the administration of desmopressin (DDAVP) may reduce blood loss after cardiac surgery. The present double-blind, randomized, placebo-controlled trial was performed to determine the effect of DDAVP on haemostasis during and after primary coronary artery bypass surgery. Fifteen patients received an infusion of DDAVP 0.3 microgram/kg and 15 patients received a placebo infusion over 15 min after cardiopulmonary bypass. Following DDAVP administration, the increase in factor VIII:C plasma level was greater than after placebo (the increase at 90 min after treatment 1.10 +/- 0.11 vs. 0.45 +/- 0.09 IU/ml, P less than 0.01). A difference between the treatments tended to occur also in the increase of von Willebrand antigen (0.64 +/- 0.08 vs. 0.23 +/- 0.07 IU/ml, P = 0.0556). A detailed evaluation of various haemostatic parameters showed no significant changes towards hypercoagulability or fibrinolysis. Inspite of the observed potential haemostatic effect of DDAVP, patients treated with DDAVP and placebo had similar postoperative blood losses (950 +/- 185 vs. 1034 +/ 321 ml), similar total haemoglobin losses (45.9 +/- 11.1 vs. 54.7 +/- 25.9 g) and similar red cell transfusion requirements (1.3 (range 0-2) vs. 1.1 (range 0 3) units). The plasma concentrations of factor F VIII:C and von Willebrand factor antigen after cardiopulmonary bypass may explain the failure to achieve a therapeutic effect with DDAVP. PMID- 1622046 TI - Peripheral excimer laser-assisted angioplasty. Preliminary clinical experience. AB - A non-thermal Xenon-Chloride excimer laser was used for peripheral arterial recanalization in eight patients with obliterating atherosclerosis of the superficial femoral artery. All patients had a total occlusion with severe claudication or pain at rest. There were three complications, which all led to thrombosis of the irradiated artery. In one, the puncture site in the artery had to be closed operatively. All vessels were followed up radiographically three months after the procedure. In seven patients the vessel was patent. Several investigators have warranted caution in using thermal lasers (continuous wave Nd:YAG or argon) for angioplasty. The non-thermal excimer laser is a viable alternative--although not without problems. Initial experiences with the new device are described. PMID- 1622047 TI - Septic complications of endoscopic laser treatment of gastrointestinal diseases. AB - This study was designated to establish the incidence of septic complications associated with Nd:YAG-laser treatment of varied gastrointestinal lesions. A total of 30 laser procedures were performed for 27 patients with both upper and lower gastrointestinal diseases. Thirty minutes after the completion of laser therapy, blood culture was obtained from each patient. Only one patient developed sepsis with fever, chills and positive blood culture, the organism isolated was Streptococcus mitis. All the other patients tolerated the treatment well and without signs of septic complications. According to this study, antibiotic prophylaxis is not necessary for gastrointestinal laser treatment. However, the conclusions must be cautious due to the small number of patients included in this study. PMID- 1622048 TI - Complications of endoscopic retrograde cholangiopancreatography in jaundiced and cholestatic patients. AB - The purpose of this prospective study was to investigate the complication rate of endoscopic retrograde cholangiopancreatography (ERCP) in the management of jaundiced and unjaundiced patients with laboratory findings suggesting cholestasis. ERCP was performed in 144 jaundiced patients and in 27 patients with unjaundiced cholestasis (age range 18-89 years, mean 66 years). Endoscopic papillotomy was performed in 45 patients, three for spasm of the sphincter of Oddi and the rest for choledochal stones. Seven bile duct prostheses were inserted endoscopically, all for treatment of malignant obstruction. The complications of ERCP were as follows: four cases of pancreatitis (2.3%), five cases of cholangitis (2.9%), two cases of bleeding (1.2%) and two perforations (1.2%). The overall complication rate was thus 7.6% (13/171) and there was no primary mortality. ERCP seems to be a safe and effective method in the diagnostic study and management of bile duct obstruction even in the elderly patients with jaundice or unjaundiced cholestasis. PMID- 1622049 TI - Acute surgical treatment of bleeding peptic ulcer. A retrospective analysis of 193 patients. AB - A retrospective analysis of 193 consecutive patients over an 11 year period operated on for continued bleeding from gastric or duodenal ulcer is presented. All patients were operated on within the first 48 hours after hospitalization. Preoperative endoscopic examination was performed in 108 patients and it was diagnostic in 79% of the cases. A sole duodenal ulcer was responsible for bleeding in 59 patients (31%) and in 50 patients (26%) the bleeding ulcer was located in the lesser curvature of the stomach. Other gastric ulcerations were scattered irregularly in different parts of the stomach. Gastric resection and Billroth II reconstruction were the most common procedures performed. Vagotomy, either truncal or gastric, was added to the resection in 31 (16%) cases. Primary mortality rate within 45 days from the operation was 15%. The survivors were on the average ten years younger (mean 58 years) than those who died. Forty one (21%) of the patients were operated on as emergency cases. These patients survived significantly better than those operated on after an observation period. It is concluded, that aggressive surgical treatment immediately after fluid resuscitation was associated with a reduction in mortality and morbidity rates in patients with bleeding peptic ulcer. PMID- 1622050 TI - Management of fulminating ulcerative colitis. AB - A series of 69 patients with fulminating ulcerative colitis (UC), treated in 1976 89, was reviewed to evaluate the lines of conservative and surgical methods used. Fifty-six of the patients (81%) were operated on during the first hospitalization period: 33 patients (48%) underwent an emergency or urgent operation, and 23 (33%) received elective surgical treatment. The mortality rate was 4.3%; three patients died after emergency operations. Excluding the 14 patients who underwent immediate surgery within the first 48 hours, a significant difference could be observed in the response to conservative treatment with and without TPN: with TPN remission was achieved in 34 of 44 cases (77%), without it in only two cases of 11 (18%), P less than 0.001. Proctocolectomy used as an emergency or urgent measure resulted in two deaths, and 93% of the patients showed complications, whereas subtotal colectomy with ileostomy resulted in no deaths and significantly fewer patients (31%) had complications, P less than 0.001. The findings suggest that TPN and bowel rest, in addition to corticosteroid treatment, may be advantageous in all cases of fulminant UC. If this 'Oxford regimen' is insufficient, subtotal colectomy with ileostomy is the safest emergency operation. PMID- 1622051 TI - Anorectal function in Crohn's disease. AB - Anorectal function was assessed in 63 patients with Crohn's disease and in 10 controls. Eleven patients with Crohn's disease (17%) were partially and three (5%) totally incontinent. The results of anal sphincter function studies of continent patients with Crohn's disease were similar to those of partially incontinent patients and controls. Incontinent patients had significantly lower maximal basal pressure (P less than 0.01) and significantly lower maximal squeeze pressure (P less than 0.05) as compared to controls. There was no significant difference in rectal capacity between continent, partially incontinent and totally incontinent patients and controls. There were significantly more patients with symptoms of anal incontinence in the group of patients with anal Crohn's disease as compared to the Crohn's group with normal anorectum (P less than 0.001). Risk factors for total anal incontinence in Crohn's disease were severe anorectal stenosis and previous surgery for anal abscesses. The most important reason for partial incontinence was diarrhoea. In conclusion, Crohn's disease without macroscopic lesions in the anorectum and without diarrhoea does not affect anorectal function. PMID- 1622052 TI - Stapling in thyroid surgery. A prospective study. AB - In a prospective study, resection of the thyroid gland by means of a linear stapling device was compared with the conventional resection technique in 12 consecutive patients with thyreotoxicosis. The median time for resection of the stapled lobe was shorter than for the conventionally resected right lobe, although the difference was not statistically significant. The median preoperative bleeding during resection of the stapled left lobe was 42 ml (range 15-126 ml), compared with 78 ml (range 34-247 ml) during the conventional resection of the right lobe (P less than 0.05). Median postoperative bleeding was somewhat less from the stapled side compared with the conventionally resected side, but did not reach statistical significance. The study thus demonstrates the feasibility of carrying out resection of the thyroid gland with a linear stapling device. The technique minimizes peroperative bleeding. It could therefore be used in thyroid surgery. PMID- 1622053 TI - Aortic valve replacement in patients aged over 70 years. AB - During a 12-year period, 58 patients aged over 70 years underwent aortic valve replacement. Sixty-six % of them had pure stenosis, 24% were with combined aortic valve disease, and six patients had only regurgitation. Preoperatively, 81% were in NYHA III and the remaining in NYHA IV. The pressure gradient in the AS-group was 105 +/- 27 mmHg and in combined-group, 99 +/- 32 mmHg. The mean ejection fraction was 54 +/- 14%. Thirty-seven mechanical and 21 biological prostheses were placed. Concomitant procedures consisted of annular dilating plasty for five patients while 16 others had coronary by-pass grafting. Hospital mortality was 12%, with the leading causes being low output syndrome and infection complications. The causes of all late deaths were non-cardiac. During the follow up period of 2.8 +/- 2.5 years, 74% of patients with mechanical valves and 62% of patients with bioprostheses were free from late complications. Prosthetic valve endocarditis (two patients) and valve failure (one patient) occurred only in patients with tissue valves. Embolic complications were equally distributed between the groups. All patients with mechanical valves were placed on permanent anticoagulation therapy, with two of them developing significant complications. On echocardiographic examination, moderate periprosthetic leakage was found in three patients, two of them having mechanical valves. There was a significant increase in EF and regression of left ventricular hypertrophy. At follow-up examination, all 47 living patients found their performance capacity improved. PMID- 1622054 TI - Lumbar disc herniation in the elderly: a rare and rewarding object for surgery. AB - We carried out a four to twelve year follow-up study in thirteen patients aged 63 years and over who were operated on for lumbar disc herniation. In eleven cases the herniation was at the L 4-5 level and in two at the L 5--S 1 level. Additional bony entrapment was present in eight cases. Simple disc removal through a small laminotomy was performed in eight patients, with a good or excellent result in four cases. Disc removal through a hemilaminectomy or laminectomy with the necessary lateral decompression of the bony entrapment gave a good or excellent result in each of the five patients. It is concluded that disc operation in the elderly usually gives acceptable late results. When even a minor bony stenosis is present at the disc herniation level, hemilaminectomy or even laminectomy should be considered. PMID- 1622055 TI - Should the glenoid be replaced in shoulder arthroplasty with an unconstrained Dana or St. Georg prosthesis? AB - Twenty-six patients, 11 with rheumatoid arthritis and 15 with osteoarthritis, have been operated on with an unconstrained total shoulder arthroplasty. Mean follow-up was 47 months. Three prostheses have been extracted. All patients stated that they had pain relief after surgery. At three year follow-up all except one had developed radiolucent zones around the glenoid component. No zones were observed around the humeral component. In shoulders with preserved glenoid surface replacement of only the humeral head might provide better long-term results than a total shoulder arthroplasty. PMID- 1622056 TI - Histology and histomorphometry of bone regeneration after experimental injuries. AB - Reparative callus formation upon tubular bone was studied after surgical injuries of different degrees. Thirty-seven young rats were divided into three groups. In the periosteum group the bone was scraped, in the fissure group we made a slit reaching the medulla, and in the defect group a standard defect was sawn. Rats were killed at 6, 12 and 18 days. The formed callus was studied histologically and histomorphometrically. The results suggest than even the primary osteochondrogenic callus formation is dependent on the mode of injury. At six days the three groups differed both qualitatively and quantitatively in regard to callus formation. At 12 and 18 days the total area of woven bone was proportional to the degree of trauma according to the linear regression line Y = 0.883 x X + 0.226 (r = 0.876, P less than 0.001). In the fissure and defect groups reparative bone filled the hole proportionally to the same extent. Periosteal and endosteal woven bone formed round the bone. Medullary bone formation was limited mainly to the area immediately adjacent to the trauma, the result being a cylinder-shaped callus. Cartilage formation was most abundant at six days and was related to the amount of woven bone in the external callus (r = 0.854, P less than 0.001) and to the trauma area (r = 0.707, P less than 0.05). PMID- 1622057 TI - Clinical features and walking ability in the early postoperative period after treatment of trochanteric hip fractures. Results with special reference to fracture type and surgical treatment. AB - The purpose of this study was to analyze the functional outcome during the early postoperative period (six weeks) in patients with trochanteric fractures. A consecutive series of 149 patients were randomized to treatment with either the DHS or Ender operative technique. 120 patients were available at review six weeks after surgery. Groups were comparable with respect to age (mean 77 years), sex ratio (73% women), type of fracture (59% and 55% unstable), experience level of the surgeon, prefracture health condition and ambulatory status. During follow-up eight patients died and there were 19 complications of neurologic and cardiovascular types equally spread among the two groups. All four infections were found in the DHS group. Orthopaedic hospital stay averaged 19 days and more patients in the Ender group could return to their previous home at time of discharge. At the six week visit 14% in the Ender group compared to 33% in the DHS group had not recovered functional walking distance (less than 15 m). All patients in the Ender group managed to walk, but 11% of the patients in the DHS group could not walk. Walking ability was most impaired for unstable fractures. It is concluded that the Ender technique will involve less operative trauma (shorter operations with less blood loss) and in the early postoperative period it can provide better conditions for walking and less need for further hospitalization than the DHS technique. PMID- 1622058 TI - Effect of perivascular sympathectomy on distal blood flow in the rabbit forepaw. A dynamic isotope experiment with Tc99m. AB - Perivascular sympathectomy, used for treating patients suffering from vasospastic disorders of the hand, is believed to cause an increase in the distal blood flow. Its effects were examined here by performing the operation on the metacarpal arteries of the left forepaw of ten New Zealand White rabbits, the right forepaw serving as a control. Blood flow was measured by Tc99m radionuclide angiography five days before the operation and three days and two and a half weeks after it. There was no statistically significant postoperative increase in blood flow in the distal parts, so that it may be concluded that at least in this experimental model, the distal sympathectomy did not have any such effect. PMID- 1622059 TI - Effect of risk factors on outcome in patients with peripheral arterial occlusive disease. PMID- 1622060 TI - Thrombogenic and vasoactive effects of smoking--with special reference to peripheral arterial occlusive disease. PMID- 1622061 TI - Differential diagnosis of intermittent claudication and the adequacy of epidemiological studies. PMID- 1622062 TI - Detection of asymptomatic arterial disease. PMID- 1622063 TI - Assessment of the microcirculation and its value for the vascular surgeon. PMID- 1622065 TI - Angiography--a diagnostic tool or a road map. PMID- 1622064 TI - Etiology and assessment of ischemia in the diabetic. PMID- 1622066 TI - Diagnosis of multilevel disease. PMID- 1622067 TI - Optimal evaluation before infrapopliteal bypass surgery. PMID- 1622068 TI - Venous evaluation for in situ bypass surgery. PMID- 1622069 TI - Differentiation between acute and acute on chronic limb ischaemia. PMID- 1622071 TI - Carotid surgery without angiography. PMID- 1622070 TI - How to select the treatment of choice in critical leg ischaemia. PMID- 1622072 TI - Optimal method for imaging of abdominal aortic aneurysms. PMID- 1622073 TI - Preoperative risk factors among vascular surgical patients. PMID- 1622074 TI - Decision analysis in vascular surgery. PMID- 1622075 TI - Intraoperative Doppler. PMID- 1622076 TI - Intraoperative angiography and endovascular ultrasound imaging. AB - Endovascular ultrasound imaging is a new technique that can be used to monitor intraoperatively the effects of balloon angioplasty or to inspect the quality of vascular reconstruction, such as endarterectomy or bypass surgery. The technique is based on high frequency ultrasonic imaging (30-40 MHz) using a rotating single element transducer mounted in an 8F catheter tip, providing 360 degrees cross sectional real time images. The clinical application is based on the high correlation between the ultrasonic images and the histological characteristics of the corresponding vessel wall tissue and lumen geometry, as has been established in previous in vitro studies. Endovascular ultrasound assessment of percutaneous angioplasty procedures or intraoperative vascular reconstruction has become an adjunct to angiographic and/or angioscopic monitoring. PMID- 1622077 TI - Outflow resistance measurements. PMID- 1622078 TI - Intraoperative flow measurements in vascular reconstruction. PMID- 1622079 TI - Angioscopy after carotid endarterectomy. PMID- 1622080 TI - Choice of intraoperative diagnostic methods. PMID- 1622081 TI - Prerequisites for screening. PMID- 1622082 TI - Is screening for abdominal aortic aneurysms worth while? PMID- 1622083 TI - Why asymptomatic carotid artery stenoses should be screened. PMID- 1622084 TI - Why asymptomatic carotid artery stenoses should not be screened. PMID- 1622085 TI - Follow-up after vascular surgery--a life-time commitment? PMID- 1622086 TI - Surveillance for failing graft. PMID- 1622088 TI - Frequency and clinical implications of recurrent carotid artery stenosis. PMID- 1622087 TI - Noninvasive impedance in graft surveillance. PMID- 1622089 TI - Smoking and factors influencing the outcome of arterial reconstruction. PMID- 1622090 TI - Who needs vascular registers? PMID- 1622091 TI - Experiences from Swedvasc/VRISS. PMID- 1622092 TI - Vascular registers in Denmark based on personal computers. PMID- 1622093 TI - National vascular registry in Finland--FINNVASC. FINNVASC Study Group. PMID- 1622094 TI - Vascular register within a well defined geographic area. PMID- 1622096 TI - Special issue on diagnosis, screening and follow-up in vascular surgery. PMID- 1622095 TI - Diagnosis, screening and follow-up in vascular surgery. PMID- 1622097 TI - Natural history of patients with peripheral occlusive arterial disease. PMID- 1622098 TI - Natural history of carotid artery disease. PMID- 1622099 TI - Natural course of abdominal aortic aneurysm. PMID- 1622100 TI - Natural history of renal artery stenosis. AB - The natural history of various types of renal artery stenosis is reviewed. Atherosclerotic renal artery stenosis is obviously a progressive disease, with a relatively high incidence of occlusions, particularly when the stenosis is narrow. Much less is known about other types of renal artery stenosis. Medial fibroplasia is obviously a disease which progresses during fertile life, but the course is rather unpredictable. Very little is known about the developmental types of renal artery stenosis. PMID- 1622101 TI - [Digestive echography is not only a diagnostic method anymore]. PMID- 1622102 TI - [Gastroduodenal tuberculosis. Report of 6 cases]. AB - The authors report a retrospective study of 6 cases suffering from gastroduodenal tuberculosis which occurred in our gastroenterology department during a period of 14 years. This affection is rare and set a lot of diagnosis problems with a gastroduodenal neoplastic affection because of its clinical polymorphism and its radio endoscopic aspects which are very confusing. The association with a localisation of another tuberculosis has been found in all cases and this allowed us to guide the diagnosis. The specific medical treatment by antibacillaires rely on histologic evidence, either by epidemiologic arguments, clinic, paraclinic and therapeutic evidence. PMID- 1622103 TI - [Diagnostic value of abdominal echography in cirrhosis of the African black. A study of 99 cases]. AB - We reviewed sonographic findings and evaluated the impact of conventional ultrasound (US) in the management of 99 consecutive black africans with liver cirrhosis. Patients were studied in the University teaching Hospital of Yaounde (Cameroon). There were 73 males and 26 females, with a mean age of 49 years (range 15 to 71 years). 90 p. cent patients presented with symptoms suggestive of liver disease. The commonest sonographic liver abnormalities were: echo coarseness with poor depiction of intrahepatic vessels, irregularity of the liver surface, hypertrophy of caudate lobe, hepatomegaly, and decreased beam penetration through the liver. Ascitis and other signs of portal hypertension were present respectively in 44 p. cent and 33 p. cent of subjects. 15 p. cent of subjects had hepatocellular carcinoma. Choletithiasis was seen in 6 subjects (6%), and chronic pancreatitis in 3 patients (3 p. cent). For 21 patients (21 p. cent), US depicted significant abdominal disease which was not clinically suspected, and for 10 patients (10 p. cent), it discovered silent liver cirrhosis. Our findings suggest that conventional US may be a useful tool in the management of some black african subjects with liver cirrhosis. PMID- 1622104 TI - [Biermer anemia associated with Kahler disease]. AB - The authors report a simultaneous observation of Biermer's anaemia and myeloma in a 77 year old woman. There are now 22 cases known to this association. A relationship between the two immunological diseases was suggested but the authors think that there is no proof of such a relationship. PMID- 1622105 TI - [Isolated intramural hematoma of the sigmoid. A rare complication of anticoagulant treatment]. AB - The authors report a case of intra-mural hematoma of the sigmoid associated with anticoagulant therapy. The small intestine is the site of predilection for intra mural hematoma and the colonic site is very unusual. Our case was revealed by an obstructive syndrome. The diagnosis, suggested by the increased prothrombin time, was confirmed by ultrasonography and endoscopy. The treatment was symptomatic with nasogastric suction and correction of any hemostatic disorders. PMID- 1622106 TI - [Hemorrhagic pseudo-cyst of the pancreas caused by erosion of the gastroduodenal artery during chronic calcifying pancreatitis]. AB - A hemorrhagic pseudo cyst of pancreas, due to a gastro duodenal artery erosion, is presented in a patient presenting a chronic pancreatitis. The diagnosis was suspected by means of clinical, ultrasound, TDM signs and was confirmed by coeliomesenteric angiography. The surgical treatment was successfully performed by local hemostasis and cystojejunal Roux-loop anastomosis. PMID- 1622107 TI - [Crohn disease and enteral nutrition: elemental or non-elemental?]. AB - Analysis of controlled trials from the literature shows that enteral nutrition is an effective treatment of active Crohn's disease. Elemental and non-elemental diets are both effective, and studies comparing the two types of mixtures have failed to reveal any significant difference. However, elemental diets appear to act more rapidly and have a more marked effect on the inflammatory syndrome and exudative enteropathy. They should therefore be preferred whenever enteral nutrition is used with the aim of influencing the inherent progression of Crohn's disease. PMID- 1622108 TI - [Current status and perspectives in intestinal transplantation]. PMID- 1622109 TI - [Development of genetic and molecular approaches for the diagnosis and the study of the pathogenic power of Helicobacter pylori, agent of inflammatory gastric diseases]. AB - Helicobacter pylori (H. pylori) is a small Gram negative bacillus, recently discovered, found in the stomach of patients with active chronic gastritis and duodenal ulcers. Production of a potent urease has been described as a trait common to all H. pylori so far isolated. To clarify the role of urease in the pathogenic process, as well as to engineer genetic tools useful for the diagnosis of H. pylori, we cloned the genes responsible for urease activity. A genomic library was constructed in Escherichia coli (E. coli) from the chromosomal DNA of the H. pylori stain 85P using a shuttle cosmid vector that we constructed in vitro capable of replicating both in E. coli and Campylobacter jejuni (C. jejuni). The genes responsible for the urease biosynthesis were cloned into E. coli host, then mobilized into C. jejuni where they were expressed. At least six different genes were shown to be required for the expression of the synthesis of an active enzyme: these genes belong to the same cluster and are regulated at the transcriptional level. The two genes encoding the two subunits of the urease enzyme were identified and sequenced; the products of these genes were compared to be other bacterial ureases. The genetic approach allowed to determine the amino-acid sequence of the most immunogenic antigens of H. pylori. In addition, it provides us with genetic tools: a 294-base pairs (bp) DNA fragment internal to one of the urease genes, was shown to be specific of H. pylori strains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1622110 TI - [Hirschsprung disease]. AB - From fourty years new knowledges about Hirschsprung's disease have dramatically transformed classical concepts of congenital megacolon. The author emphasizes successive steps of knowledges from his personal experience of 500 patients observed at Pediatric Surgical Department, Hopital des Enfants Malades, Paris, and his own contribution at several research programs on this topic. They concern Radiology, Manometry, Histochimy, Immunocytochimy. Using technics of molecular biology, recent progress in knowledge of neural crest cells migration towards myenteric plexus, light etiopathogenesis of the disease. Several pathological associations suggest the genetic origin of the neuro transducers defect. Whatever be the scientific interest of it, clinical lethal risk of early enterocolitis remains a daily evidence. Simple routine precocious deflation of colonic hyperpression is still the most important message to be stressed. PMID- 1622111 TI - Immunohistochemistry, in situ hybridization and polymerase chain reaction (PCR) in detecting c-myc expression in human malignancies. AB - The assessment of oncogene expression at cellular level is important in understanding the role of those genes in carcinogenesis. Using in situ hybridization and immunohistochemistry, the expression of oncogenes can be visualized in topographic relation to tissue morphology. In the present study, c myc overexpression was studied in ten carcinomas of different origin (6 mammary adenocarcinomas, 2 vulvar and 2 bronchial squamous cell carcinomas) by in situ hybridization (ISH) with 35S-labeled RNA probes and by immunohistochemistry (IHC). DNA amplification and transcription of c-myc oncogene were also studied with polymerase chain reaction (PCR) using beta-globin as an intrinsic standard for DNA amplification. The effect of formalin fixation of c-myc expression was simultaneously studied. Half of the tumours (5/10) demonstrated c-myc mRNA overexpression by ISH performed on frozen sections and two of the samples were shown to over-express c-myc protein by IHC. Only two samples fixed in formalin showed positive signals for c-myc mRNA. None of the biopsies showed DNA amplifications either with ISH or PCR. The present results suggest that ISH with RNA probes is a useful method for detecting the transcription of activated oncogenes in malignant tissues, especially when applied on frozen sections. The results also indicate that in some cases, c-myc gene may be adequately transcribed to mRNA but the latter is not translated to the appropriate oncoprotein. PMID- 1622112 TI - Peritumoural IL-4 treatment induces systemic inhibition of tumour growth in experimental melanoma. AB - We have examined the ability of interleukin-4 (IL-4) to inhibit the growth of the B.16 melanoma in C57BL/6 mice. Tumours were allowed to become established and then treated locally with 50 ng/day IL-4. Treatment was continued for 7 days and then the tumours were removed and weighed. The results showed that recombinant murine IL-4 (rmIL-4) strongly inhibited tumour growth, with some complete resolutions. In addition, the effect of IL-4 treatment was seen to be systemic; in mice bearing two tumours (neck and thigh), which had been innoculated simultaneously, treatment at the neck site resulted in reduced tumour growth at both sites. This effect was accompanied by an increase in the proportion of lymphocytes in the spleen, particularly T-cells, although tumours at neither site showed much evidence of leucocytic infiltration. These results suggest that local treatment with IL-4 is able to profoundly reduce the rate of tumour growth, even of nodules not receiving treatment directly. PMID- 1622114 TI - Antiestrogenic effects of Z-1, 1-dichloro-2,3 diphenyl-2-(4 methoxyphenyl)cyclopropane(5a) on human breast cancer cells in culture. AB - Compound 5a ([Z]-1, 1-Dichloro-2,3 diphenyl-2-(4-methoxyphenyl)cyclopropane) is a novel cyclopropyl compound which was shown to be a pure antiestrogen. In the present study, the antiproliferative activity of 5a was examined on estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 human breast cancer cells and A-549 human lung cancer cells using the hemocytometric trypan blue exclusion method. Compound 5a inhibited the growth of MCF-7 cells in a dose-related manner over a concentration range of 10(-9) to 10(-5) M, but did not alter the growth of MDA-MB-231 or A-549 cells. Co-administration of estradiol (10(-8) M) reversed the antiproliferative activity of 5a (10(-7) M) on MCF-7 cells. Further, an ER dependent mechanism of action is supported by the specific ER binding of 5a in MCF-7 cells observed in this study. The influence of 5a on the cell surface morphology of MCF-7 and MDA-MB-231 cells was studied using scanning electron microscopy (SEM). Compound 5a at 10(-6) M reduced the length and density of microvilli (MV) on MCF-7 cells, which was reversed by co-administration of estradiol (10(-8) M). This compound did not alter the cell surface morphology of ER-negative MDA-MB-231 cells. In conclusion, 5a and tamoxifen inhibited the growth of ER-prositive MCF-7 cells in an estradiol-reversible manner, and had no effect on ER-negative MDA-MB-231 cells. The results of this study with human breast cancer cells suggest that 5a may be highly effective in the treatment of estrogen-dependent breast cancer and/or in the prophylactic treatment of women with a high risk of breast cancer development. PMID- 1622113 TI - Response of subpopulations of the FSall C fibrosarcoma to low dose x-rays and various potential enhancing agents. AB - The effectiveness of various oxygen carrying treatments in sensitizing subpopulations of the FSallC fibrosarcoma to low doses of radiation was assessed, and compared with survivals obtained with the same cells after in vivo irradiation under normally oxygenated or hypoxic conditions. FSallC tumors were treated with 2-10 Gray then the Hoechst 33342 dye diffusion method was used to separate the tumor into bright (enriched in normally oxygenated cells) and dim (enriched in hypoxic cells) subpopulations. There was good agreement between the survival of normally oxygenated cells in culture and bright cells from tumors and between hypoxic cells in culture and dim cells from tumors over a radiation dosage range of 2-5 Gray. At 10 Gray bright cells from tumors were minimally less sensitive to the radiation dose than normally oxygenated cells in vivo. When maximally effective doses of perfluorochemical emulsions (F44E at 4 g PFC/kg or Fluosol-DA at 2.4 g PFC/kg) or a purified bovine hemoglobin solution (PBHS at 1.32 g protein/kg) were administered 1 hr. prior to radiation therapy with carbogen (95% O2, 5% CO2) breathing prior to and during radiation delivery, low single doses of x-ray (2-5 Gray) were measurably more cytotoxic toward both FSallC tumor cell subpopulations. These results indicate that perfluorochemical emulsions or purified bovine hemoglobin preparations along with carbogen breathing may be able to increase tumor radiosensitivity to the relatively low radiation doses per fraction used in the clinic. PMID- 1622115 TI - Weekly regimen of 5-FU vs 5-FU + intermediate dose folinic acid in the treatment of advanced colorectal cancer. AB - Sixty-four patients with advanced colorectal cancer were randomized to receive 5 fluorouracil (5-FU) at the dose of 600 mg/sm weekly or the same regimen of 5-FU administered halfway through a 1 hour i.v. infusion of folinic acid (FA) at the dose of 200 mg/sm. A partial remission (PR) was obtained in 1/30 patients (3%) treated with 5-FU and in 9/34 patients (26%) treated with 5-FU + FA (P = 0.028). The objective response was accompanied by an improvement in subjective status and general conditions. The median duration of PR in 5-FU + FA arm was 10 months (range: 6-17). The median time to progression was 5 and 6 months in patients treated with 5FU and 5FU + FA, respectively (not a statistically significant difference). There were no cases of grade 4 toxicity. A higher, but not statistically significant, incidence and intensity of diarrhoea was observed in the 5-FU + FA arm. However, 14 patients on 5-FU + FA as opposed to 3 on 5-FU had to stop the treatment temporarily because of side-effects (P = 0.011). Median survival was higher with 5-FU + FA treatment (10 vs 7 months), but the difference is not statistically significant. This study confirms that the addition of an intermediate dose of FA enhances the cytotoxicity of 5-FU. Although its clinical advantage was limited, this weekly 5-FU + FA regimen appears useful in the treatment of advanced colo-rectal cancer on a outpatient basis. PMID- 1622116 TI - Amplification of the N-myc oncogene in an adenocarcinoma cell line of the lung. AB - Myc gene abnormalities were studied in 30 human lung cancer cell lines. N-myc gene amplification was found in an adenocarcinoma cell line, VMRC-LCD. Neither c- or L-myc gene amplifications nor K-ras codon 12, 13, 61 point mutations were observed in this tumor. Cytomorphologically the VMRC-LCD cells had positive characteristics of typical adenocarcinoma, and the carcinoembryonic antigen in the culture medium was strongly positive. N-myc gene amplification in adenocarcinoma of the lung is extremely rare, therefore we report herein on this case. PMID- 1622117 TI - Fluorescent location of abnormal cells in cell smears obtained from the lungs of patients with lung cancer. AB - A bronchoscope fitted with a brush was used to collect cells from patients with lung tumours. The cells were either made into smears or deposited as monolayers on microscope slides. Using a fluorescent probe for the cell surface enzyme, referred to as guanidinobenzoatase, abnormal cells were readily distinguished from normal cells which lacked this enzyme. PMID- 1622118 TI - The effect of Dilazep on F10 cells in vitro. AB - Experiments on F10 cell growth, colony ability, cell adhesion and ultramorphology at SEM have been performed. The effect of Dilazep (DIL) has been compared with that of well known modulating agents such as Flunarizine (FLU) and Verapamil (VER) on cells cultured in high Ca++ medium (HCM) and in low calcium medium (LCM). While in HCM there is no difference among the three drugs, FLU and VER had a stronger effect on cell growth inhibition in LCM. Cell adhesion to the growth substratum, evaluated by the technique of spontaneous detachment in culture medium, is reduced in DIL treated cells in comparison to the controls. PMID- 1622119 TI - Interaction of cytotoxic agents: a rule-based system for computer-assisted cell survival analysis. AB - The actual effectiveness of environmental noxious agents or anticancer drugs can be fully determined only by knowing if the effects (in the present case, the cytotoxic effects) induced by a given agent are enhanced by exposure to another (or other) agent(s). Given a certain combination of agents, it is possible to distinguish three types of interaction: (a) zero interaction or additivity; (b) positive interaction or synergism; and (c) negative interaction or antagonism. In this work, the methodological problems involved in evaluating the type and level of interaction between biologically active agents are discussed and an "intelligent" approach to the problem is proposed. In particular, a prototype of a computer-assisted rule based system, named CISA (Cytotoxic Interaction and Survival Analysis), designed in a KES environment (Knowledge Engineering System) and implemented on a personal computer, is described. By constructing isoboles based on experimental cell survival data and taking into account the relative confidence intervals, the system can indicate the appropriate combinations of dosages to be tested and finally determine the type and level of interaction. The system, which represents an attempt to administer "intelligently" the experimental data, is therefore able to identify the best strategy of analysis, to carry out the data processing and to offer suggestions to the investigator about the usefulness of the data and the planning of further experiments. PMID- 1622120 TI - Postoperative adjuvant immunochemotherapy and infiltration of dendritic cells for patients with advanced gastric cancer. AB - To determine the group of patients for whom a biological response modifier is useful, the efficacy of postoperative adjuvant immunotherapy was investigated with regard to infiltration of dendritic cells (DC) in patients with advanced gastric cancer who underwent absolute curative resection. The infiltration of DC was classified into marked and slight. The chemotherapy group was prescribed mitomycin C and tegafur, while for the immunochemotherapy group a biological response modifier, PSK, was also prescribed in survival between the chemotherapy and immunochemotherapy groups. In patients with slight infiltration, however, the 5 - year survival rates were 0% in the chemotherapy and 15% in the immunochemotherapy group. Patients given PSK survived longer than those given chemotherapy only (P less than 0.05). Therefore, adjuvant immunotherapy may be considered for patients with advanced gastric cancer with slight infiltration of DC. PMID- 1622121 TI - Multidrug resistance in Yoshida rat ascites hepatoma cell lines. AB - Rat ascites hepatoma (AH) cell lines that were induced by dimethylaminoazobenzene and established as transplantable tumors had different sensitivities to vinblastine (VBL). The most VBL-resistant cells, AH66, showed more cross resistance to vincristine and anthracyclines than AH66F cells. The resistance of AH66 cells was significantly decreased by verapamil. VBL-resistance of AH66 cells was inhibited by other drugs reported as overcoming acquired multidrug resistance, while the sensitivity of AH66F cells was hardly influenced by these drugs. The lowered uptake and enhanced extrusion of the antitumor drug in AH66 cells were suppressed by verapamil. M(r) 160,000 protein in the plasma membrane from AH66 was labeled with a photoactive VBL analog and was immunopositive to a monoclonal antibody against P-glycoprotein, C219. The sensitive cells had barely detectable levels of the surface membrane components. Specific photo-labeling with a VBL analog of P-glycoprotein of AH66 cell membrane was inhibited by reserpine and verapamil which restored the VBL resistance. These results indicate that AH66 cells are a naturally acquired multidrug-resistant cell line overexpressing a P-glycoprotein, and AH cell lines are useful to study multidrug resistance of hepatic carcinomas and development of counteracting drugs. PMID- 1622122 TI - Increasing peak levels of vinblastine given in repeated divided doses. AB - Pharmacokinetics of vinblastine were assayed in 9 patients, using a high pressure liquid chromatography method. Patients were treated in three different ways: the first 3 patients received bolus injections of vinblastine at a fixed dose of 2 mg/day for 5 consecutive days. Three other patients were treated with 3 mg/m2 vinblastine as a bolus injection on day 1, day 3 and day 8. The remaining 3 patients received a bolus injection of vinblastine of 6 mg/m2 on day 1, day 8 and 15. Blood samples were taken on days 1, 3 and 5 for the first group and on every treatment day for the other groups. The early phase peak levels obtained during the 5 day-treatment increased progressively during repeated treatments, probably due to decreased central compartment volumes and not to drug accumulation. There was no relation between vinblastine levels and orosomucoid levels. The rise in peak level was less predictable during the other methods of treatment (once or twice weekly). This observation calls attention to the necessity of performing drug level monitoring at very early time points, as increasing peak levels during repeated administration may explain unexpected toxicities. PMID- 1622123 TI - Stable expression of a cDNA encoding rat brain protein kinase C-beta I confers a multidrug-resistant phenotype on rat fibroblasts. AB - Protein kinase C (PKC) is a Ca++- and phospholipid-dependent protein kinase that plays an important role in signal transduction pathways that regulate cell growth. Tumor cells selected for a multidrug resistant (MDR) phenotype often express elevated levels of PKC activity. To directly test whether PCK overexpression can produce an MDR phenotype, we studied rat embryo fibroblasts that were infected with the full-length cDNA clone RP58 encoding the beta I form of rat brain PKC. The PKC-beta I gene recipient R6-PKC3 cells are stable, overproduce PKC, and express an elevated level of PKC activity. R6-PKC3 cells exhibited significant resistance to adriamycin, actinomycin D, vinblastine, and vincristine but not to 5-fluorouracil. Intracellular accumulation of adriamycin, vinblastine, and vincristine was decreased in the R6-PKC3 cells, but this was not associated with an altered level of P-glycoprotein expression. Moreover, the reduction in drug accumulation appeared to be a consequence of a decreased rate of drug uptake. The data indicate that overexpression of PKC in rat fibroblasts produces an MDR phenotype without altering P-glycoprotein expression. PMID- 1622124 TI - The immunomodulatory beta-galactoside-specific lectin from mistletoe: partial sequence analysis, cell and tissue binding, and impact on intracellular biosignalling of monocytic leukemia cells. AB - Nanogram quantities of the beta-galactoside-specific lectin from mistletoe (ML-I) that is composed of two different types of subunits exhibit immunomodulatory potency and enhance cytokine secretion in vitro and in vivo. Partial sequence analysis of the carbohydrate-binding B chain revealed a ragged N-terminus and overall homologies to the B subunit of Ricin D and Ricin E. Two evolutionarily neutral substitutions were apparent in the otherwise identical N-terminal sequences of the two toxic chains within the lectin preparation. On the basis of the influence of chemical modification by group-specific reagents on ligand binding, the lectin was biotinylated with biotinyl-N-hydroxysuccinimide ester to allow monitoring of cell binding. Monocytic leukemia cells (THP-1) specifically bound the lectin with positive cooperativity at low lectin concentrations. Radiolabelled lectin could be found in several organs and in an experimental solid tumor in biodistribution in mice. Its presence in a notable amount in spleens is especially noteworthy with respect to the already reported immunomodulation. To determine intracellular responses that precede the lectin dependent augmentation of cytokine secretion, phosphorylation of proteins and phospholipids as well as Ca(2+)-mobilization were assessed in THP-1 cells. Quantitative increases of [32P]-phosphate incorporation were determined for a 28 kDa protein and for phosphatidylinositol-4,5-biphosphate. Similarly, the fluorescence activity of the intracellular Ca(2+)-indicator fluo-3 is elevated by approximately 25% after lectin treatment. Apparently, cell binding of the lectin is followed by modulation of biosignalling processes. PMID- 1622125 TI - Sex steroid receptors, S-phase fraction and DNA ploidy as determinants of the risk of relapse and death of female breast cancer. AB - S phase fraction (SPF) and DNA ploidy were related to disease outcome by a separate analysis of sex steroid receptor positive and negative tumours in a series of 232 patients with breast carcinoma followed-up for over 8 years in our clinic. SPF was significantly higher in receptor-negative tumours than in receptor-positive ones (p = 0.037). SPF predicted recurrence only in ER+ or PR+ patients (p = 0.02-0.003). Recurrence-free survival (RFS) was significantly related to SPF only in ER+ (p = 0.001) and PR+ (p less than 0.001) tumours. In survival analysis, ER+ (p = 0.002) and PR+ (p less than 0.001) patients were efficiently divided into prognostic groups by SPF, whereas in ER- and in PR- tumours SPF had only suggestive predictive value. In N- tumours, SPF predicted recurrence-free survival and disease-related survival in ER+ (p = 0.003) (p = 0.039) and in PR+ (p = 0.003) (p = 0.012) tumours, respectively, whereas in ER-, PR-, tumours, SPF had no predictive value. In pN+ tumours, SPF also predicted survival in ER+ (p = 0.03) and in PR+ (p = 0.024) tumours. Thus the prognosis of ER+ or PR+ tumours with an SPF less than 9% is favourable with a risk of death of about 20%, in contrast to that of about 70% in tumours with an SPF greater than 9% during the follow-up period. To conclude, the proliferation rate as measured by S phase fraction by FCM is a highly significant prognostic factor in breast cancer. The prognostic value of S phase fraction is confined to steroid receptor positive tumours, whereas in receptor-negative tumours SPF has no predictive value. The results thus suggest that all women with steroid receptor-negative breast tumours and those receptor-positive tumours with an SPF higher than 9% should be subjected to postoperative adjuvant chemotherapy immediately. PMID- 1622126 TI - Interrelation between Western type cancers and non-Western type cancers as regards their risk variation in time and space. IV. Hormonal transition of Japanese women from the pro-cervical cancer age through the pro-endometrial cancer age to the pro-hypogonadism age. AB - Chronological trend of urinary steroid excretions in Japanese women was investigated during the period of June 1972 to August 1986 using healthy women of urban and rural origins, patients with breast cancer and patients with either cervical cancer or endometrial cancer. The excretions of 14 neutral steroids were estimated by gas liquid chromatography, and the obtained data were tentatively correlated with the epidemiological backgrounds. In the course of the chronological transition from the 1st stage (1972-1974) to the 2nd stage (1975 79), the urinary steroid pattern of Japanese women with and without cancer experienced a common change to produce specific deviations that were in agreement with the hormonal characteristics of a pill user or of an endometrial cancer patient. At the 3rd stage (1980-86), patients with either cervical cancer or endometrial cancer were distinguished from 1st stage controls by non-specific depression of all androgens, progestins and corticosteroids in urine. Throughout the whole period, both the risk for cervical cancer and the reproductive activity (birth rate) were found to decrease continuously in Japanese women. Evidence was presented to suggest that the above deterioration of the hormonal environment in Japanese women could be related to the stress of modern life rather than to defects in the diet. On the basis of the above findings, the 1st, 2nd and 3rd stages of our investigation were tentatively termed the pro-cervical cancer age, the pro-endometrial cancer age and the pro-hypogonadism age. The relation between the chronological change of urinary steroids and that of the epidemiological background was analyzed from the view point of population ecology. PMID- 1622127 TI - Cytosolic and nuclear androgen receptors in colorectal adenomas. AB - The aim of this study was to verify the presence of androgen receptors (AR) in human colorectal adenomas and in normal adjacent mucosa, and to determine whether there is any difference in AR tissue content between females and males. Our data show higher levels of nuclear AR in normal mucosa than in adenomas (p less than 0.001). A significant difference was also present in males between normal and pathological tissue both in cytosolic (p less than 0.05) and nuclear receptors (p less than 0.01). In female subjects this difference was also evident, but not significant. Our results seem to support the hypothesis of protective effects of androgens in colonic mucosa. PMID- 1622128 TI - Circulating mucins as tumor markers in ovarian cancer (review). AB - Because a highly sensitive and specific serum marker for ovarian carcinoma has not been reported, it is unlikely that there will be an application of serum markers for screening for this disease in asymptomatic women. However, many oncologists use serum tumor markers initially to differentiate epithelial ovarian carcinoma from benign gynecological conditions prior to surgery, so as to ensure appropriate surgical referral, and then to monitor the clinical course of disease during and after adjuvant therapy. The most commonly performed tumor marker assay in ovarian cancer (CA125) has been extremely valuable in patient management, but this marker is also elevated in a considerable proportion of patients with benign gynecologic diseases and endometriosis, and a relatively small proportion of patients with early stage disease. A new class of serum tumor markers, the highly glycosylated, high molecular weight mucins, have enormous potential in the management of ovarian cancer patients, since the use of assays for these markers may overcome many of the problems associated with CA125. Indeed, when used in combination with CA125, some mucin-based assays have increased the sensitivity and specificity of detection, thereby eliminating many false positive results seen with patients with benign disease and endometriosis, and also predicted disease recurrence in the majority of patients before clinical symptoms became apparent. These markers are the subject of this review, with particular attention to the commercially-available mucin-based assays. PMID- 1622129 TI - An evaluation of CA 549, a circulating marker of breast cancer using a procedure for comparison with CA 15.3. AB - A serum assay of CA 549 (Hybri-BREScan CA 549 degrees, Hybritech), a new tumor marker, was performed in 129 patients with breast cancer and 35 healthy women, in parallel with CA 15.3 (ELSA-CA 15.3 degrees, CIS Biointernational). Comparing 95 women with primary breast carcinoma and 35 controls, Relative (or Receiver) Operating Characteristic (ROC) analysis revealed that the Area Under ROC Curve (AUC) of CA 15.3 was significantly higher than that of CA 549, indicating that, for our population, the first marker was more effective. Parallel and series analyses were also performed using ROC AUC and revealed that the combination of these two tests did not give more information than the CA 15.3 test alone; however, they did not in any way constitute diagnostic tools. In our experience, the best field of application for CA 549 seems to be the therapeutic monitoring and early detection of breast cancer recurrences. However, further investigations on a larger scale are necessary to assess more precisely the place of CA 549 in following the clinical course of breast cancer patients. PMID- 1622130 TI - Prognostic significance of flow cytometric and clinical variables in endometrial adenocarcinoma stages I and II. AB - In a prospective study comprising 447 women with endometrial carcinoma stages I II, the prognostic significance of clinical and flow cytometric variables was evaluated in univariate and multivariate analyses. The parameters studied included age, uterine cavity depth, clinical stage, histopathologic grade, myometrial invasion, weight, body mass index (BMI), parity, diabetes, oestrogen treatment, DNA - content and S-phase fraction. Patient selection for surgery influenced prognosis with a better survival in operated patients. In the univariate analysis the following parameters correlated with survival: age, grade, myometrial invasion, DNA - content and S- phase fraction. In the multivariate analyses which included clinical variables only, age, grade and myometrial invasion remained significant, but when flow cytometric variables were added, only S-phase fraction and myometrial invasion contained prognostic information. S-phase fraction also generally correlated with time of recurrence. PMID- 1622131 TI - Large scale expansion of human tumor infiltrating lymphocytes with surface modified stimulator cells for adoptive immunotherapy. AB - Expansion of tumor infiltrating lymphocytes (TIL) in vitro is hampered by several factors, including a limited amount of lymphocytes obtained from different tumors, unknown target antigens and limited supply of antigen-presenting cells (APC) which are generally believed to be essential in the classical way of T cell stimulation and expansion. In approaching these difficulties, we have recently used surface-oxidized allogeneic PBL to stimulate the TIL periodically in the presence of a low dose of rIL-2 (200 IU/ml). TIL derived from 22 (out of 23) tumor specimens could be expanded with 20 -10(7) fold increases over 6-16 weeks to a sufficient amount of 10(9) -10(11) cells for adoptive immunotherapy. In contrast, only 2-100 fold increase were observed in six tumor specimens (out of 23) when 200 IU/ml rIL-2 was used only. The phenotypes, autologous tumor reactivity and cytolytic capability of TIL propagated with surface-oxidized stimulators were similar to those expanded in the presence of IL-2 alone. These data suggest that expanding TIL with surface-modified stimulator cells could be a useful alternative method to obtain a large amount of tumor specific cytolytic T cells for clinical immunotherapeutic use, irrespective of tumor-antigen stimulation and MHC restriction. PMID- 1622132 TI - Chlorophyllin, an antimutagen, acts as a tumor promoter in the rat dimethylhydrazine colon carcinogenesis model. AB - Chlorophyllin (CHL), the water soluble sodium/copper salt of chlorophyll, was investigated for its effect on colorectal cancer risk in the rat-dimethyldrazine colon carcinogenesis model. Ninety weanling Fisher 344 male rats were treated with five weekly injections of 1,2 dimethylhydrazine (DMH), 20 mg base/kg body weight. Rats had been previously divided into three groups, consuming either rat chow and water (Group I), rat chow and CHL 1.5 mM in water throughout the experiment (Group II), or water and rat chow during DMH injection, adding CHL 1.5 mM to the drinking water after completion of the DMH treatments. At sarcifice, the incidence and yield of colorectal tumors were as follows: Group I 10% and 0.1; Group II, 23% and 0.27; and Group III, 47% and 0.53 (p less than 0.005 for incidence and = 0.003 for yield). These data demonstrate that, though it is well established that CHL is an antimutagen, CHL in this colorectal carcinogenesis model acted as a tumor promoter. PMID- 1622133 TI - Evaluation of the safety of recombinant interleukin-2 (rIL-2) and rIL-2 plus 5 fluorouracil (5-FU) in the adjuvant treatment of gastric cancer patients. AB - Eight patients received either recombinant Interleukin-2 (rIL-2) alone or rIL-2 plus 5-Fluorouracil (5-FU) by constant infusion after undergoing potentially curative surgery for gastric cancer. rIL-2, given at a dose of 18 x 10(6) IU/m2/24 hours, was safely tolerated and only two episodes of WHO grade 3 toxicities occurred, both of which promptly responded to treatment and temporary interruptions of rIL-2 infusions. 5-FU infusions given at 12.5 mg/kg/24 hours did not alter the rebound lymphocytosis seen after completion of rIL-2 infusions. We conclude that the administration of rIL-2 and rIL-2 plus 5-FU to cancer patients recovering from major surgery is safe and well tolerated. PMID- 1622134 TI - Dopa inhibits induced proliferative activity of murine and human lymphocytes. AB - L-DOPA, the product of enzymatic hydroxylation of L-tyrosine, is released by melanotic melanoma cells in vivo and in vitro. Here we report that DOPA at pharmacologically relevant micromolar doses dramatically inhibits the stimulation of DNA synthesis by lipopolysaccharide and concanavalin A in murine splenocytes and human lymphocytes, having little or no effect on unstimulated (control) lymphocytes or proliferating fibroblasts. Therefore we propose that melanogenically active melanoma cells can inhibit the host's immune response via the release of DOPA and/or its oxidation products. PMID- 1622135 TI - Stress response, survival and enhancement of heat sensitivity in a human melanoma cell line treated with L-canavanine. AB - L-Canavanine, like other aminoacid analogs, induces the synthesis of heat shock proteins (HPSs) but, unlike heat or other stressing agents, it fails to induce thermotolerance. We have studied the synthesis and the intracellular distribution of HSPs induced by canavanine, the effects of this analog on the viability and thermal sensitivity of a human melanoma cell line (M14) and the capacity of canavanine-induced HSPs to self regulate their own synthesis. Evidence indicates that the HSP induction is time--and dose--dependent and, also in the presence of arginine, is not associated with the development of thermotolerance. On the contrary, cells become more heat sensitive and are less efficient in the control of the feed-back mechanism that regulates HSP synthesis. The possible utilization of this substance as a potential aid for the treatment of tumors, in association with heat, was examined. PMID- 1622136 TI - Induction of HLA class II antigens in osteosarcoma cells by interferons and tumor necrosis factor alpha. AB - In this study we have evaluated the ability of interferons (IFNs) alpha, beta, gamma and Tumor Necrosis Factor (TNF) alpha to modulate the expression of the Major Histocompatibility Complex (MHC) antigens in human osteosarcoma cells. The osteosarcoma cell lines Saos-2 and U-2 OS, treated in vitro with IFNs and TNF alpha, showed an increased expression of class I HLA antigens. However, only IFN gamma and, to a lower extent, IFN beta induced the expression of class II HLA antigens. These effects were dose and time-dependent. Simultaneous treatment with IFN gamma and IFN beta or TNF alpha, which by itself was unable to induce the expression of class II HLA antigens, produced different effects on the two osteosarcoma cell lines: in Saos-2 IFN beta and TNF alpha amplified the effects obtained with IFN gamma alone; in U-2 OS, TNF alpha increased the expression induced by IFN gamma on class II HLA antigens, whereas IFN beta antagonized the effects of IFN gamma. IFN alpha did not influence the induction of class II HLA antigens by IFN gamma in the two osteosarcoma cell lines. IFNs have been introduced in some clinical protocols for the treatment of osteosarcoma, based on their antiproliferative activity. Our findings may contribute to a better knowledge of the effects of IFNs and TNF alpha in osteosarcoma by showing the existence of more complex interactions. PMID- 1622137 TI - The induction of apoptosis by chemotherapeutic agents occurs in all phases of the cell cycle. AB - A1.1 T-cell hybridoma cells exposed to either actinomycin D (1 microgram/ml), camptothecin (200 ng/ml) or aphidicolin (10 micrograms/ml) for 16 hrs at 37 degrees C die via apoptosis. The cell death was independent of RNA synthesis, in contrast to previous data reported for other forms of apoptosis in murine lymphocyte cells and their derived lines. Each of the three agents described appeared to induce death in all phases of the cell cycle in asynchronously proliferating cells. G1 cells appeared to be more susceptible to the effects of camptothecin and contrasts with other reports which detail its selectivity for S and G2 phase cells. This might indicate that cells are progressing into S phase before dying or, alternatively, cells may indeed be dying in G1. When elutriated synchronised cells were exposed to each of the three cytotoxic agents cell death occurred in all phases of the cell cycle. In view of the fact that G1 and S phase cells did not cycle to any appreciable extent during drug exposure, it was likely that ensuing death, occurred specifically from these phases. G2/M cells, however, moved rapidly into G1 in the presence of each drug, thus making it difficult to determine whether G2/M cells were capable of undergoing drug-induced apoptosis. To overcome this problem, nocodazole (50 ng/ml) was used to block asynchronous cells in M phase. When these cells were exposed to actinomycin D, aphidicolin or camptothecin, cell death ensued via apoptosis. PMID- 1622138 TI - Growth factor-like activity of phenol red preparations in the MCF-7 breast cancer cell line. AB - Hormonal responsiveness of the estrogen-sensitive MCF-7 human breast cancer cell line is known to vary between laboratories although the causes and implications of these variations remain unclear. Our findings lead us to conclude that the pH indicator phenol red (PHR) has growth factor-like effects in addition to its well known estrogen-like effects. To demonstrate this hypothesis, we have assessed the importance of PHR either in the absence or in the presence of the estrogens contained in the serum added to the culture medium. The basal growth rate of MCF 7 cells was significantly reduced by short-term or long-term withdrawal of PHR. The stimulatory effects of estradiol and the inhibitory effects of the antiestrogen 2-CH3,4-OH-tamoxifen (MHT) were not significantly affected by long term withdrawal of the dye. Moreover, long-term cell maintenance without PHR alone or in complete estrogen-depleted medium did not change their basal steroid receptor content. The molecular structure of the estrogen receptor which is usually modified under estrogenic stimulation remained identical whether or not the cells were maintained in the presence of the dye. Maintaining cells without the dye in the presence of serum estrogens led to the death of the cell line after 50 transfers. Lastly, addition of PHR had clearcut growth stimulatory effects on the hormono-independent cell line Evsa-T. PMID- 1622139 TI - Reduction of VX2 transplanted tumor by granulocyte depletion using extracorporeal circulation on rabbit models. AB - To investigate the role of granulocytes and the effect of granulocytosis on malignancies, we studied the relationship between white blood cell and granulocyte (Gr) counts, and tumor size. As we have reported that cancer patients with high granulocyte (G/L) ratio have a poor clinical prognosis, normalization of the G/L ratio could contribute to improvement in their condition. Tumor bearing rabbits treated with the extracorporeal granulocytte depletion device showed a decrease in tumor size and no tumor necrosis. Tumor-bearing rabbits with no extracorporeal granulocyte depletion showed a remarkable tumor progression and an increase in Gr count. Depletion of granulocytes considerably improved the survival ratio of tumor-bearing animals. The device used in this study could be a potential treatment for malignant tumors. PMID- 1622140 TI - Hyperthermochemoradiotherapy for esophageal cancer (review). AB - Hyperthermia is effective for the treatment of cancer when applied concomitantly with chemotherapy and irradiation. However, it is difficult to heat deep portions of the body including the esophagus. Cancer of the esophagus still poses considerable treatment problems, with a poor 5-year survival rate after surgery, an even worse outlook after radiation and surgery, and a not very satisfactory response to chemotherapy. We, therefore, devised an electrode for radio frequency, and we have been successfully using this electrode in the treatment of esophageal cancer. The 5-year survival rates of patients with esophageal cancer, given either preoperative hyperthermochemoradiotherapy or chemoradiotherapy, were 43.2 and 14.7%, respectively. Immediate improvement of subjective complaints and decrease or elimination of the cancer lesion are so distinct that this treatment, by means of an endotract antenna, shows promise as a modality for esophageal lesions. PMID- 1622141 TI - Recombinant human interleukin-3 opposes the effects of vitamins A and D on HL-60 human myeloid leukaemia cells. AB - Interleukin-3 (IL-3), retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (calcitriol) (vitamin D) have achieved objective responses in phase I/II clinical trials in myeloid leukaemia and preleukaemia patients. In an effort to explore any additive or synergistic interactions between these biological agents which could provide the basis for improved therapeutic regimens for myeloid leukaemia patients, we have investigated the effects of IL-3 on both RA- and vitamin D induced actions in HL-60 human myeloid leukaemia cells, which have receptors for these three agents, in both clonogenic microassays and liquid suspension cultures. The proliferative stimulus of IL-3 overrode and reversed the antiproliferative actions of both RA and vitamin D, the latter being more sensitive to the counter-acting effect of IL-3. Whereas only high concentrations of IL-3: 1000 or more U/ml were able to oppose the antiproliferative effect of RA, all concentrations of IL-3 including the low concentration of 10 U/ml, significantly counteracted the anti-proliferative action of vitamin D. RA restrained the proliferative stimulus of IL-3 partly at low physiological concentrations and almost completely at high pharmacological concentrations. The same results were reproduced in liquid suspension culture. Whereas RA restrained the proliferative stimulus of IL-3, vitamin D failed to restrain it. However, IL 3 did not induce differentiation or affect RA- or vitamin D-induced differentiation of HL-60 cells. The present results suggest that the clinical use of the combination of low concentration of IL-3 with RA and not with vitamin D might restrain the progression of myeloid leukaemia incurred during the treatment with IL-3 in some preleukaemic patients. PMID- 1622142 TI - Effect of hypoxia and acidosis on the cytotoxicity of mitoxantrone, bisantrene and amsacrine and their platinum complexes at normal and hyperthermic temperatures. AB - In an effort to synthesize drugs which would become much more cytotoxic at clinically achievable hyperthermic temperatures, complexes of the tetrachloro platinum(II) dianion were made with two anthracene dye derivatives, MITOX and BISANT, and the acridine dye derivative m-AMSA. As compared with the parent drug, PtCl4(MITOX)2 was less cytotoxic at 37 degrees C and more cytotoxic at 42 degrees C and 43 degrees C especially at pH 6.45. In contrast, the PtCl4(BISANT)2 was more cytotoxic than BISANT under all conditions. M-AMSA was again shown to be less cytotoxic at elevated temperatures but PtCl4(m-AMSA)2 was more cytotoxic especially at 43 degrees C and pH 6.45. Platinum levels in cells treated for 1 hr with 25 microM at 37 degrees C, 42 degrees C and at pH 7.40 versus pH 6.45 demonstrated no significant differences depending on temperature or pH except for PtCl4(MITOX)2 where approximately 4 times higher intracellular platinum levels were present at pH 6.45 versus pH 7.40, although this finding did not correlate with cytotoxicity. These results suggest that PtCl4(MITOX)2 and PtCl4(m-AMSA)2 may be highly interactive drugs with local hyperthermia. PMID- 1622143 TI - Antitumor agent, physalin F from Physalis angulata L. AB - Physalin F and physalin D were isolated and characterized from the ethanolic extract of the whole plant of Physalis angulata L. (Solanaceae). Systematic fractionation of the ethanolic extract of the plant led to characterization of physalin F from the fraction PAIV-2 as an active ingredient which showed cytotoxicity in vitro by DEA and MTT assays on 8 cancer cell lines, five human cancer cell lines: HA22T(hepatoma), HeLa(cervix uteri), KB(nasopharynx), Colo 205(colon) and Calu-1(lung); and three animal cancer cell lines: H1477(melanoma), Hep-2(laryngeal) and 8401(glioma). It was found that the anti-hepatoma action is the strongest, and the anti-HeLa is the next. Physalin F also had an antitumor effect in vivo against P388 lymphocytic leukemia in mice whereas physalin D was inactive both in vitro and in vivo. PMID- 1622144 TI - A role for plasma membrane potential in doxorubicin--induced cytotoxicity. AB - Using a modifier of membrane function, we have shown that plasma membrane potential plays an important role in doxorubicin (DOX) - induced cytotoxicity through its connection with cell metabolism and through its effect on drug accumulation. Membrane potential of K562 cells, measured using 3, 3'-dihexyl oxacarbocyanine (DiOC6 (3)), was increased in the presence of non-toxic cepharanthin or N-1379 and decreased in the presence of non-toxic K252a. Correlated with the level of the potential, DOX efficacy was enhanced by cepharanthin or N-1379 and decreased by K252a associated with an increase or decrease of the percentage of cells in S-phase and of intracellular DOX accumulation. PMID- 1622145 TI - Combination of beta-interferon and tamoxifen as a new way to overcome clinical resistance to tamoxifen in advanced breast cancer. AB - This paper shows that the response to tamoxifen (T) can be improved and the resistance to the antiestrogen can be overcome, in advanced breast cancer, by a pretreatment with natural beta-interferon (nIFN-beta) followed by the association of nIFN-beta with T. Forty-three patients with advanced breast cancer, both progressive (group A) and stable or partially responsive (group B) to previous treatment with T received nIFN-beta i.m. 3 x 10(6) IU/day for 14 days and, subsequently, T30 mg/day and nIFN-beta once a week. The overall objective response rate was 26% (95% Confidence Interval = 13-39) with 8 PR obtained in group A and 3 CR in group B. The median duration of response was 6 months (range 3-12+). Stabilization of disease was observed in 44% of cases. Toxicity was mild. PMID- 1622146 TI - Tolerance to long-term treatment of malignant midgut carcinoid with a highly purified human leukocyte alpha-interferon. AB - We report here the long-term toleration of treatment with a highly purified human leukocyte alpha-interferon (Interferon Alfanative) in patients with midgut carcinoid tumours with liver metastases. During an 18-month period, 13 consecutive patients with this diagnosis commenced treatment with a-interferon. Five patients died during the first 2 years of treatment due to tumour progression, and in 2 patients the treatment with a-interferon had to be stopped due to severe adverse effects (mainly joint pain and tiredness). Hence, 6 patients tolerated the treatment for a long-term period (greater than 2 years), and in these patients the treatment has continued for more than 3 years; in 3 of them for more than 4 years. In these 6 patients, adverse effects of mild or moderate degree have been observed in 2 patients: itching and hair loss in one and joint pain and hair loss in another. Except for a significant reduction in the blood number of WBC and thrombocytes (although in no patient did leukocytopenia or thrombocytopenia develop) and the development of hypothyroidism in one patient, no biochemical tests have shown significant changes during the long-term treatment. In these 6 patients, objective tumour regression has been observed in 2 patients, stable disease in 3 patients and progression in 1 patient. We conclude that, of the patients initiated on treatment with a interferon for midgut carcinoids with liver metastases, only approximately 50% are still on the treatment after 2 years. These patients, on the other hand, may continue for a longer period of time with a low degree of adverse effects. PMID- 1622147 TI - The expression of mRNA for glucocorticoid receptor gene and functional glucocorticoid receptors detected in PA-III rat prostate adenocarcinoma cells. AB - The metastatic capacity of PA-III rat prostate adenocarcinoma cells has been well documented, although little is known about the biological and biochemical characteristics of PA-III cells. This study characterizes PA-III cells with regard to the presence or absence of glucocorticoid and androgen receptors. Cytosols of PA-III cells possessed [3H]-dexamethasone binding sites with association constant (Ka) 0.46 +/- 0.17 x 10(9) M-1 and number 341 +/- 175 fmols/mg protein. Displacement of [3H]-dexamethasone binding from PA-III cytosols achieved by increasing doses of unlabelled dexamethasone, corticosterone, cortisol, progesterone, deoxycorticosterone and aldosterone documented glucocorticoid binding specificity. Northern and dot blot analyses detected the expression of mRNA for glucocorticoid receptor using a 750 bp cDNA probe of the glucocorticoid receptor gene. Twenty-four hours incubation of PA-III cells with increasing amounts of dexamethasone resulted in a remarkable inhibition of the growth of PA-III cells. Binding studies with [3H]-R1881 as well as dot blot and Northern blot analyses using a 500 bp cDNA probe of androgen receptor gene could not detect the presence of androgen receptors in PA-III cells. The present study documented functional glucocorticoid receptors in the androgen-independent PA-III rat prostate adenocarcinoma cells. These results suggest that glucocorticoids may regulate important aspects of androgen-independent prostate cancer cells growth and functions. PMID- 1622148 TI - Penta-acetyl geniposide: isolation, identification and primary effect on C6 glioma cells in vitro. AB - A new compound, penta-acetyl geniposide [(Ac)5-GP], was obtained from modified extract of Gardenia Fructus (San-jee-chee in Chinese). Spectral studies including ultraviolet (UV), mass (MS), nuclear magnetic resonance (NMR), infrared (IR) and elemental analysis (EA) have suggested the chemical structure of the compound as 1-(beta-D-2',3',4',6'-tetraacetyl- glucopyranosyloxy)-1,4a,5,7a-tetrahydro-7 (acetomethyl)-c yclopentapyran-4-carboxylic acid methyl ester. The antitumor bioactivity of (Ac)5-GP in vitro was studied. It exhibited the activities of reduced plating efficiency and inhibition of DNA synthesis in cultured C-6 glioma cells, but had little effect on RNA and protein synthesis. These results implied that the acetylated iridoid glycoside of Gardenia Fructus is biologically active as an antitumor agent against C-6 glioma cells in culture. PMID- 1622149 TI - Growth inhibitory and differentiating effects of sodium butyrate on human neuroblastoma cells in culture. AB - The effect of sodium butyrate (NaB) on cell growth and expression of morphological and biochemical properties was examined in the human neuroblastoma cell lines AF8 and SJ-N-KP. The obtained data show that NaB induced a marked growth inhibition and morphological differentiation, while it was ineffective in inducing biochemical differentiation. PMID- 1622150 TI - Therapeutic efficacy of interleukin-2 activated killer cells against adriamycin resistant mouse B16-BL6 melanoma. AB - Development of multidrug-resistance (MDR) remains a major cause of failure in the treatment of cancer with chemotherapeutic agents. In our efforts to explore alternative treatment regimens for multidrug-resistant tumors we have examined the sensitivity of MDR tumor cell lines to lymphokine activated killer (LAK) cells. Adriamycin (ADM) resistant B16-BL6 melanoma, L1210 and P388 leukemic cell lines were tested for sensitivity to lysis by LAK cells in vitro. While ADM resistant B16-BL6 and L1210 sublines were found to exhibit at least 2-fold greater susceptibility to lysis by LAK cells, sensitivity of ADM-resistant P388 cell was similar to that of parental cells. Since ADM-resistant B16-BL6 cells were efficiently lysed by LAK cells in vitro, the efficacy of therapy with LAK cells against the ADM-resistant B16-BL6 subline in vivo was evaluated. Compared to mice bearing parental B16-BL6 tumor cells, the adoptive transfer of LAK cells and rIL2 significantly reduced formation of experimental metastases (P less than 0.009) and extended median survival time (P less than 0.001) of mice bearing ADM resistant B16-BL6 tumor cells. Results suggest that immunotherapy with LAK cells and rIL2 may be a useful modality in the treatment of cancers with the MDR phenotype. PMID- 1622151 TI - Effect of metabolic inhibitors, methylxanthines, antioxidants, alkali metals, and corn oil on 1,2-dimethylhydrazine carcinogenicity in rats. AB - The effect of the oral administration of 10 compounds on 1,2-dimethylhydrazine (DMH) carcinogenesis was investigated in 180 male Wistar rats and 510 male BD6 rats. DMH, administered s.c. once per week for 20 consecutive weeks (20 mg/kg body wt/dose), produced intestinal (mainly colon) tumors of various histological type in 100% of both rat strains and, in addition, caused Zymbal gland carcinomas in 79.7% of Wistar rats. Pretreatment with disulfiram (DSF, 500 mg/kg), a known inhibitor of DMH metabolism, totally prevented intestinal and Zymbal gland tumors in Wistar rats. When DSF treatment started after the first DMH injection, the protective effect was not total, the incidence and multiplicity of both types of tumors being comparable to those observed following a single injection of the carcinogen alone. This confirms the involvement of DSF in the initiation stage only of DMH carcinogenesis. A complete prevention of intestinal tumors in BD6 rats was also produced not only by the DSF metabolite carbon disulfide (250 mg/kg) but also by the hepatotoxic agent carbon tetrachloride (1.5 ml/kg), which suggests that the block of DMH metabolism in rat liver is not an exclusive property of thiono-sulfur compounds. Butylated hydroxytoluene (BHT) decreased the multiplicity of intestinal tumors, but not to a significant extent. BHT and the aforementioned metabolic inhibitors were administered by gavage in corn oil, which per se did not significantly decrease intestinal or Zymbal gland tumors. All remaining modulators were administered with drinking water. Two additional antioxidants triggered opposite effects on the multiplicity of intestinal tumors. In fact, sodium selenite (10 mg/l) significantly decreased the number of tumors, whereas ascorbic acid (10 g/l), irrespective of its combination with CaCl2, produced a marked enhancement. The alkali metal salts CaCl2 and KCl (both at 5 g/l) as well as the methylxanthines caffeine and theophylline (both at 600 mg/l) were devoid of significant effects. Neither treatment with DMH alone nor its association with test modulators was accompanied by significant changes in body weight gain or survival of animals. On the whole, depending on the mechanisms involved, the comparative study of test compounds led to a broad array of effects on DMH carcinogenesis, ranging from complete inhibition to significant enhancement. The resulting picture can be visualized at a glance in Figure 1 of this article. PMID- 1622152 TI - Morphologic differences in leukemic cells (L1210) exposed to 1-beta-D arabinofuranosylcytosine and daunorubicin. AB - To compare the morphologic differences in leukemic cells exposed to a nucleotide synthesis inhibitor and a DNA strand damage inducer, L1210 cells incubated with 1 beta-D-arabinofuranosylcytosine (ara-C) or daunorubicin (DNR) were investigated by time-lapse video microscopy, flow cytometry and transmission electron microscopy. At 1.0 microgram/ml of ara-C, cells could be separated into two populations, with some becoming ballooned and deformed, i.e. irreversibly damaged, and others remaining unchanged, i.e. in a proliferative state. In contrast, at 0.10 microgram/ml of DNR, nearly all cells were remarkably enlarged and did not proliferate during 72 hours of observation. Such morphologic changes induced at clinically achievable concentrations of each agent seemed to reflect their differing mechanisms of action on the synthesis of DNA. The methods described may allow the characterization of antileukemic agents as well as the development of clinical designs for their rational application in leukemia patients. PMID- 1622154 TI - Experimental tumor inhibitory and toxic properties of the mitomycin A analogue 7 (2-hydroxyethoxy) mitosane (BMY-25551). AB - BMY-25551, 7-(2-hydroxyethoxy)mitosane, was selected from a series of mitomycin A (MMA) analogues for more detailed study. As with other members of this class, it was shown to be 8 to 20 times more potent than mitomycin C (MMC) in cytotoxicity to murine and human tumor cell lines in vitro, in causing DNA cross links in vitro, and in dose levels for tumor inhibition in vivo. BMY-25551 appeared to be more effective in tumor inhibition than MMC against P388 leukemia and B16 melanoma in mice and comparable to MMC against L1210 leukemia and Madison 109 lung carcinoma. BMY-25551 was also comparable to MMC in hematologic depression in mice. Factors affecting its possible utility in humans are discussed. PMID- 1622153 TI - Immunomodulators from Paris formosana Hayata. AB - Eight glycosides PF-1 to PF-8 were isolated from the leaves and stems of Paris formosana Hayata (Liliaceae), of which PF-3 (III) was the main compound. It was found that PF-1 to PF-3 (I-III) caused proliferative responses of mouse lymphocytes to concanavalin A and augmentation of mouse granulocyte/macrophage colony forming cells in mouse fibroblast cell L929 conditioned medium. PF-4(IV) and PF-8 showed significant immunomodulatory effects with very low toxicity: they not only caused the same immune responses as PF-1, 2 & 3 but also enhanced the proliferative response of human peripheral whole blood to phytohemagglutinin. PF 5 (V) also increased 3H-thymidine incorporation in ConA-stimulated lymphocytes and in PHA-stimulated human peripheral whole blood, and enhanced the proliferative response of granulocyte/macrophage colony stimulating activity. PF 6(VI) and PF-7(VII) augmented 3H-thymidine incorporation in granulocyte/macrophage colony-forming cells and mitogenic response of PHA stimulated human peripheral whole blood cells from healthy adults. However, PF-1, 2 and 3 showed hemolytic action, while PF-4 to PF-8 had no hemolytic action at all. On the other hand, the hemolytic action of PF-3 derivatives was reduced as compared with PF-3 but their immune responses did not equal those of PF-3, only showing granulocyte/macrophage colony stimulating activity. PMID- 1622155 TI - Activation and phenotyping of LAK generated by exposure to product of cells transformed by interleukin 2 cDNA. AB - It has been previously found that local administration of X63-m-IL-2 cells transformed by interleukin 2 (IL-2) cDNA and constitutively producing large quantities of IL-2 mediated regressions of murine plasmacytomas and 3-methyl cholanthrene-induced sarcomas transplanted in syngeneic mice. Here we show that killer cells generated by cultivation of spleen cells in supernatants from X63-m IL-2 cultures (LAK) or by co-cultivation of murine splenocytes with X63-m-IL-2 cells were cytolytic for natural killer (NK)-sensitive as well as NK-resistant target cells, including the IL-2-producing X63-m-IL-2 cells. Spleen cells cultured in X63-m-IL-2 supernatants or co-cultivated with X63-m-IL-2 cells yielded predominantly Thy 1.2+, CD3+, LFA-1+ lymphocytes. The in vitro results suggest that the LAK cells generated due to the IL-2 production by genetically engineered cells probably help to terminate the treatment by killing the IL-2 producers. PMID- 1622156 TI - Growth inhibition of human malignant glioma cells in vitro by agents which interfere with biosynthesis of eicosanoids. AB - In an attempt to find new methods for the treatment of malignant gliomas a number of tests have been performed to learn whether growth of such cells in vitro may be affected by agents which interfere with the biosynthesis of eicosanoids. It was observed that DNA-synthesis of short-term monolayer cultures could be blocked by compounds which inhibit cyclooxygenase and/or lipoxygenase dependent arachidonic acid metabolism. The strongest inhibitory activities were noted in serum-free culture medium using compounds interfering with the activity of lipoxygenases. One explanation of these results could be that the growth of human malignant gliomas is dependent on certain eicosanoids which may be synthesized by the malignant cells themselves. PMID- 1622157 TI - Neoglycoprotein binding to normal urothelium and grade-dependent changes in bladder lesions. AB - Chemical conjugation of carbohydrate derivatives to a labelled carrier protein makes it possible to monitor the presence of specific sugar-dependent binding to routinely processed tissue sections. Different levels of cytoplasmic staining were observed in normal urothelium for the applied probes that expose a beta-D galactoside, alpha- or beta-N-acetyl-D-galactosaminide, beta-N-acetyl-D glucosaminide, alpha-D-mannoside, alpha-L-fucoside or a-D-glucoside, respectively. These moieties are crucial parts of the recognition sites in cellular glycoconjugates for plant lectins. The extent of staining invariably increased from the basal to the luminal cell layer. No nuclear staining was observed. Within the 18 cases of bladder lesions studied, the appearance of nuclear staining was characteristic of transitional cell carcinoma, its correlation to the histologic grade being dependent on the type of neoglycoprotein. Cytoplasmic staining revealed at least two patterns of grade dependent variations, namely rather constant expression for lactose-mannose-, fucose- and maltose-specific sites and an initial increased followed by a loss of binding activity at the highest level of cellular atypia for the other three types of probe. Intratumoral heterogeneity was especially visible in tumors of this group. Interestingly, the known positive correlation of presence of the Thomsen-Frieden rich antigen with the level of cellular atypia, monitored with peanut agglutinin, could be extended to the expression of respective receptor sites, which was experimentally feasible due to the synthesis of this disaccharide structure and its immobilization to the carrier protein. PMID- 1622158 TI - 1H-NMR spectroscopy of urinary components of SHN mice in the course of spontaneous mammary tumourigenesis. AB - Proton nuclear magnetic resonance (1H-NMR) spectroscopy of urine was studied before and after the development of spontaneous mammary tumours in SHN mice. Urinary allantoin and lactic acid levels declined from 2 weeks before mammary tumour appearance and increased with the tumour growth after its appearance. The level of component at 3.4 ppm, which reacted with Ninhydrin and was possibly assigned to taurine, continued to decline beginning 2 weeks before tumour appearance. No considerable changes were observed in urinary levels of creatine and creatinine before and after tumour development, however, these components as well as allantoin or lactic acid had positive correlations with mammary tumour size. A negative correlation was observed between the level of 3.4 ppm component and tumour size. Surgical removal of tumours resulted in an apparent decline in urinary levels of allantoin and lactic acid. At all stages, urinary allantoin level was approximately 4 times as high as the levels of lactic acid and 3.4 ppm component. All results suggest that urinary allantoin would be a good indicator for the development of spontaneous mammary tumours of mice. PMID- 1622159 TI - Identification of a clustering of chromosomal breakpoints in the analysis of 203 human primary solid tumor non specific karyotypic rearrangements. AB - The distribution of 271 chromosomal breakpoints involved in 203 clonal structural non "specific" rearrangements identified in 82 human primary solid tumors of various histologies has been analyzed. According to the "mean + 1 SD" criterion the normalized breakpoint frequency was significantly higher for chromosomes 1p, 3p, 3q, 4q, 6q, 7q, and 11p. Clusters of 3 or more breakpoints were assigned to only 24 of the 329 bands (7%) of the standard karyotype, and 9 high density breakpoint segments have been identified. These results indicate that a nonrandom pattern of chromosomal rearrangements can be extracted from the complex karyotypic changes observed in solid tumors, which suggest that the involved regions play a general role in tumorigenesis. PMID- 1622160 TI - Bactericidal titers of loracarbef (LY 163892) in serum and killing rates in volunteers receiving 400 versus 200 milligrams. AB - In a randomized crossover trial, six volunteers received 200- and 400-mg doses of loracarbef (LY 163892), a new oral cephalosporin. Mean +/- standard error of the mean concentrations in serum obtained after 1.5 and 3 h were 13.2 +/- 2.8 and 4.3 +/- 0.7 mg/liter, respectively, after the 400-mg dose and 6.9 +/- 1.0 and 1.7 +/- 0.2 mg/liter, respectively, after the 200-mg dose. Bactericidal reciprocal titers measured against respiratory pathogens in serum suggested that loracarbef would be highly effective against Streptococcus pneumoniae and Streptococcus pyogenes (median titers, 8 to 128 at 1.5 h and less than 2 to 32 at 3 h) and beta lactamase-negative Haemophilus influenzae (median titers, 4 at 1.5 h and 2 to 4 at 3 h). Other species (Branhamella catarrhalis, Streptococcus anginosus, Staphylococcus aureus) were associated with lower bactericidal titers. Killing curves performed against 12 strains demonstrated that the bioactivity of loracarbef (measured by the reduction in the area under the control growth curve) was significantly correlated with the concentration/MIC ratio, whereas the initial rate of killing was not, once the concentration was greater than the MIC. Our results suggest that administration of 400 mg of loracarbef every 8 h might be associated with more favorable pharmacodynamic parameters against target bacteria. PMID- 1622161 TI - Construction of a water-soluble form of penicillin-binding protein 2a from a methicillin-resistant Staphylococcus aureus isolate. AB - The mecA gene from methicillin-resistant Staphylococcus aureus 27r, which encodes the membrane-bound penicillin-binding protein 2a (PBP 2a), was cloned, sequenced, and expressed in Escherichia coli. PBP 2a is the major factor that mediates methicillin resistance in staphylococci. The DNA sequence of the mecA gene from strain 27r was greater than 99% identical to the DNA sequence of other S. aureus mecA genes and the mecA gene from Staphylococcus epidermidis. Analysis of the deduced amino acid sequence of PBP 2a from strain 27r revealed a hydrophobic region at the amino terminus that possessed characteristics of an uncleaved signal peptide such as those found in type II integral membrane proteins. Site specific mutagenesis was used to modify the strain 27r mecA gene to permit removal of the region encoding the putative transmembrane region (amino acids 2 to 22). When it was expressed in E. coli, the modified mecA gene from strain 27r encoded a water-soluble form of PBP 2a that was detectable in the cytoplasm of transformants. The water-soluble form of PBP 2a protein from S. aureus 27r retained the same binding efficiency for beta-lactam antibiotics as the unmodified membrane-bound PBP 2a from S. aureus 27r. PMID- 1622162 TI - Correlation of various in vitro testing methods with clinical outcomes in patients with Bacteroides fragilis group infections treated with cefoxitin: a retrospective analysis. AB - There is limited information regarding the correlation of anaerobic susceptibility testing and outcome in the treatment of Bacteroides fragilis infections. We retrospectively analyzed the clinical outcomes of B. fragilis infections in patients treated with cefoxitin; the analysis was blinded for susceptibility results. Isolates of B. fragilis were tested by multiple agar dilution methods, disk elution, and commercial broth microdilution methods. Of 19 patients analyzed, 11 were cured and 8 were treatment failures. No significant differences existed between the groups with respect to age, sex distribution, weight, APACHE II score, dose of cefoxitin, or bacteremia. Failure was associated with a longer cefoxitin dosing interval (P = 0.019), a longer duration of hospitalization (P = 0.038), and decreased duration of cefoxitin treatment (P = 0.05). Four agar dilution systems (brucella plus blood, Wilkins-Chalgren, Wilkins Chalgren plus blood, brain heart infusion plus blood) and two broth systems (Wilkins-Chalgren microdilution and a commercial system [Micromedia; Beckman, Carlsbad, Calif.]) all demonstrated lower geometric mean MICs for isolates from the group of patients that could be cured. Only the commercial broth microdilution medium (Micromedia) demonstrated a significantly reduced geometric mean MIC (P = 0.056). By using a logistic regression analysis, the shorter cefoxitin dosing interval (P = 0.0004) and the lower geometric mean MIC (P = 0.0088) in the commercial broth microdilution system were shown to be independent predictors of treatment success. These data suggest that the time that the concentration of cefoxitin is over the MIC for B. fragilis may be an important predictor of treatment success. PMID- 1622163 TI - Duration of rifampin chemoprophylaxis for contacts of patients infected with Haemophilus influenzae type B. AB - Rifampin is recommended as a prophylactic treatment for intimate contacts of young children who develop invasive infections with Haemophilus influenzae type B (Hib). A 4-day course of rifampin (20 mg/kg of body weight per day, not to exceed 600 mg as a maximum single daily dose) is 95% effective in eradicating pharyngeal colonization with Hib, thus effectively reducing the risk of both associated patients and recurrent illness in index patients less than 2 years old. This study compares rates of eradication of pharyngeal colonization with Hib for 2- and 4-day courses of rifampin therapy. One hundred sixty-three patients with Hib infection were treated at Children's Hospital of Pittsburgh between January 1986 and December 1988; prophylaxis was recommended for 128. Participating families were randomized to receive either 2- or 4-day therapy. Throat swabs were obtained from contacts prior to therapy. Repeat cultures were obtained from colonized contacts 2 days after completing rifampin and again on all contacts 7 to 10 days after completing therapy. Of 68 participating families, 34 received 2-day and 34 received 4-day therapy with rifampin. Twenty-two of 24 colonized contacts in the 2-day group and 17 of 18 in the 4-day group had negative cultures for Hib on follow-up. Two-day therapy with rifampin appears to be as effective as 4-day treatment in the eradication of Hib pharyngeal colonization. PMID- 1622164 TI - Antagonism between isoniazid and the combination pyrazinamide-rifampin against tuberculosis infection in mice. AB - Mice that had been inoculated intravenously with 6.30 log10 Mycobacterium tuberculosis H37Rv 14 days earlier were administered one of three combinations of drugs, i.e., isoniazid (INH)-rifampin (RMP)-pyrazinamide (PZA), INH-RMP, and RMP PZA, during an initial 2-month period to mimic the initial phase of chemotherapy for human tuberculosis and during a later 4-month period to mimic the continuation phase of chemotherapy. At the end of the initial phase, all three combined regimens were found to have been highly effective in terms of the number of CFUs in the spleens of infected mice. The bactericidal activities of INH-RMP PZA and INH-RMP were similar, whereas that of RMP-PZA was significantly greater. The spleens of all of the mice that had been treated initially with INH-RMP-PZA were culture negative by the end of 6 months of treatment, regardless of the regimen employed during the continuation phase. However, after an additional period of 6 months without treatment, the proportion of spleen culture positivity, or relapse rate, was significantly smaller in the subgroup treated with RMP-PZA during the continuation phase than in the subgroups treated with INH RMP-PZA or INH-RMP; the relapse rate did not differ significantly between the latter two subgroups. These results suggest that antagonism occurs between INH and the combination RMP-PZA during both the initial and continuation phases of chemotherapy, compromising the benefit conferred by the addition of PZA to the combined regimen. The preliminary pharmacokinetic analysis suggested that the pharmacological interaction between INH and RMP was very likely to be involved in the mechanism of antagonism, as concomitant treatment with INH had significantly reduced the peak serum level and the area under the serum concentration-time curve of RMP in mice. PMID- 1622165 TI - Pharmacokinetics of cefepime after single and multiple intravenous administrations in healthy subjects. AB - The pharmacokinetics of cefepime in 31 young, healthy volunteers were assessed after the administration of single and multiple 250-, 500-, 1,000-, or 2,000-mg intravenous doses. Each subject received a single dose of cefepime via a 30-min intravenous infusion on day 1 of the study. Starting from day 2, subjects received multiple doses of cefepime every 8 h for 9 days, and on the morning of day 11, they received the last dose. Serial blood and urine samples were collected after administration of the first dose and on days 1, 6, and 11. Cefepime concentrations in plasma and urine were assayed by using reverse-phase high-performance liquid chromatography with UV detection. Data were evaluated by noncompartmental methods to determine pharmacokinetic parameters. The mean half life of cefepime was approximately 2 h and did not vary with the dose or duration of dosing. The regression analyses of peak levels (Cmax) in plasma at the end of the 30-min intravenous infusion and the area under the plasma concentration versus-time curve (AUCo-infinity) showed a dose-proportional response. The steady state volume of distribution (Vss) was approximately 18 liters and was independent of the administered dose. The multiple-dose pharmacokinetic data are suggestive of a lack of accumulation or change in clearance of cefepime on repeated dosing. Cefepime was excreted primarily unchanged in urine. The recovery of intact cefepime in urine was invariant with respect to the dose and accounted for over 80% of the dose. The values for renal clearance ranged from 99 to 132 ml/min and were suggestive of glomerular filtration as the primary excretion mechanism. It is concluded that cefepime linear pharmacokinetics in healthy subjects. PMID- 1622166 TI - Nucleotide sequence and phylogeny of the tet(L) tetracycline resistance determinant encoded by plasmid pSTE1 from Staphylococcus hyicus. AB - The nucleotide sequence of the tetracycline resistance (tet) gene and its regulatory region, encoded by the plasmid pSTE1 from Staphylococcus hyicus, was determined. The tet gene was inducible by tetracycline and encoded a hydrophobic protein of 458 amino acids. Comparisons between the predicted amino acid sequences of the pSTE1-encoded Tet from S. hyicus and the previously sequenced Tet K variants from Staphylococcus aureus, Tet L variants from Bacillus cereus, Bacillus stearothermophilus, and Bacillus subtilis, Tet M variants from Streptococcus faecalis and Staphylococcus aureus as well as Tet O from Streptococcus mutans were performed. An alignment of Tet amino acid sequences revealed the presence of 30 conserved amino acids among these Tet variants. On the basis of the alignment, a phylogenetic tree was constructed. It demonstrated large evolutionary distances between the Tet M and Tet O variants on one hand and the Tet K and Tet L variants on the other hand. The pSTE1-encoded Tet proved to be closely related to the Tet L proteins originally found on small Bacillus plasmids. The observed extensive similarities in the nucleotide sequences of the tet genes and in the deduced Tet amino acid sequences allowed the assignment of the pSTE1-encoded Tet to the Tet proteins of class L. PMID- 1622167 TI - In vitro evaluation of E1077, a new cephalosporin with a broad antibacterial spectrum. AB - E1077 is a novel parenteral cephalosporin with a wide spectrum of potent antibacterial activity against aerobic and anaerobic gram-positive and gram negative bacteria. Against methicillin-susceptible Staphylococcus aureus, E1077 was twice as active as cefpirome, with an MIC for 90% of strains tested (MIC90) of 0.78 micrograms/ml. Methicillin-resistant S. aureus was moderately to highly resistant to E1077, but E1077 was at least twice as active as other beta-lactams tested. Against Enterococcus faecalis, E1077 was the most active of the cephalosporins tested (MIC90, 12.5 micrograms/ml) and was at least fourfold more active than cefpirome and ceftazidime. At concentrations of less than or equal to 0.78 micrograms/ml, E1077 inhibited 90% of streptococci and most of the members of the family Enterobacteriaceae tested, with the exceptions of Serratia marcescens and Proteus vulgaris, for which the MIC90s of E1077 were both 3.13 micrograms/ml. Against Pseudomonas aeruginosa, E1077 was two- to fourfold more active than cefpirome and ceftazidime. For the anaerobes, E1077 was as active against Bacteroides fragilis as was cefuzonam, and its activity was fourfold higher than those of cefpirome and ceftazidime. E1077 was at least as resistant as cefpirome to hydrolysis by various beta-lactamases, and these enzymes had a low affinity for E1077. PMID- 1622168 TI - Effects of cefetamet (Ro 15-8074) on Treponema pallidum and experimental syphilis. AB - Cefetamet pivoxil (Ro 15-8075) is a newly developed, expanded-spectrum cephalosporin that is orally active. In vitro, the active form, cefetamet (Ro 15 8074), at a concentration of 0.05 micrograms/ml killed and lysed Treponema pallidum. Rabbit serum did not diminish its effectiveness. The antibiotic rapidly entered the circulation following intramuscular injection into rabbits, attaining its highest levels of 24 to 37 micrograms/ml within 10 to 30 min. Animals were infected intradermally with T. pallidum and then treated with different doses of cefetamet. Accelerated healing was detected following treatment with 15 and 30 mg/kg of body weight. The antibiotic was also effective in killing organisms that had disseminated to distant tissues. In three separate sets of experiments, rabbits were infected with treponemes and then treated with cefetamet intramuscularly at 1, 15, or 30 mg/kg as follows: (i) after lesions had just become clinically apparent, (ii) after lesions were enlarged and well developed, or (iii) prior to the appearance of clinical lesions. Antibiotic effectiveness was determined by sacrificing the animals 1 week after antibiotic treatment and examining splenic tissue for residual, disseminated treponemes. Cefetamet was treponemicidal in all three situations. Maximum effects occurred when the antibiotic was injected before lesions had become clinically apparent (incubation period). These results suggest that cefetamet pivoxil might be useful for treating syphilitic infections. PMID- 1622169 TI - Assay of fluconazole by high-performance liquid chromatography with a mixed-phase column. AB - A mixed-phase liquid chromatographic column was used to assay fluconazole in plasma, serum, and cerebrospinal fluid. The assay was linear from 0.2 to 20 micrograms/ml, with an average coefficient of variation of less than 5%. The partitioning of the drug between serum and cerebrospinal fluid was determined for 34 patients. The method was demonstrated to be suitable for both pharmacokinetic studies and monitoring of patients receiving treatment with this antifungal agent. PMID- 1622170 TI - Pharmacokinetics of L-671,329 in rhesus monkeys and DBA/2 mice. AB - The time course of plasma drug levels and urinary recovery for two lipopeptide antifungal antibiotics, L-671,329 and cilofungin, were measured in male rhesus monkeys (Macaca mulatta) and in female DBA/2 mice. The antibiotics were administered intravenously at 10 mg/kg of body weight in phosphate-buffered saline-26% polyethylene glycol for the rhesus monkeys and in 5% dimethyl sulfoxide for the mice. Plasma and urine drug concentrations were determined by high-pressure liquid chromatography and/or a microbiological assay versus Aspergillus niger, and pharmacokinetic parameters were determined for both species. In each of the two rhesus crossover tests as well as in the mouse studies, the pharmacokinetics of the two compounds were similar; however, a marked difference was evident between species. The half-lives of L-671,329 and cilofungin in plasma were 39 and 34 min in the mice and averaged 1.8 and 2 h in the rhesus monkeys, respectively. In mice and rhesus monkeys, urinary recovery was less than 4% for both compounds. PMID- 1622171 TI - Identification and cloning of a tetracycline resistance gene from the fish pathogen Vibrio salmonicida. AB - Vibrio salmonicida is the causative agent of cold-water vibriosis in farmed Atlantic salmon. We cloned a 6.9-kb PstI fragment from the 170-MDa plasmid (pRVS1) containing a tetracycline resistance determinant. A subcloned 1.96-kb HindIII fragment was found to mediate the tetracycline resistance. The 2.5-kb ClaI-PvuI fragment carrying the Tet E determinant from Escherichia coli hybridized under stringent conditions with the cloned 1.96-kb HindIII fragment from V. salmonicida. The 1.96-kb HindIII fragment codes for a protein of 26.5 kDa which represents a candidate for the structural TetA protein of the class E determinant. Deletion of a 0.28-kb BalI fragment from the middle of the HindIII fragment resulted in the loss of tetracycline resistance. We were able to show that when E. coli carries the cloned 6.9-kb PstI fragment, expression of tetracycline resistance is regulated by the concentration of tetracycline in the medium. In contrast, tetracycline resistance was constitutively expressed in the E. coli isolate carrying the 1.96-kb HindIII fragment. The tetracycline resistance gene isolated from the 170-MDa R plasmid of the marine fish pathogen V. salmonicida was characterized and shown to be a class E determinant. PMID- 1622172 TI - Influence of angiotensin II-induced alterations in renal flow on excretion of cefonicid in isolated perfused rat kidneys. AB - The effects of variations in renal perfusate flow on the excretion of cefonicid was examined in isolated perfused rat kidneys. Cefonicid, an expanded-spectrum cephalosporin, is primarily eliminated by active tubular secretion and is neither metabolized nor reabsorbed in the isolated kidney. We used angiotensin II (AII), a strong vasoconstrictor hormone of the afferent and the efferent arterioles in the kidney, to determine whether the renal and secretion clearances, as well as the excretion ratio (ER = CLR/[fu x GFR], where CLR is renal clearance, fu is the unbound fraction, and GFR is glomerular filtration rate), of this low-extraction compound can be altered by a decreased perfusion flow. Control studies were performed in the absence (n = 5) and presence (n = 4) of AII; cefonicid studies were performed in the absence (n = 4) and presence (n = 5) of AII. AII (1 to 4 ng/min) and cefonicid (5 to 10 micrograms/min) were infused into the perfusate. Cefonicid was assayed by high-performance liquid chromatography, and its protein binding was determined by ultrafiltration. AII decreased the perfusate flow rate and increased the renal vascular resistance and filtration fraction of the isolated kidney in the presence and absence of cefonicid. The glomerular filtration rate remained unchanged among the groups. The fractional excretion of glucose was low and steady, indicating a well-preserved tubular function. Although the unbound fraction was unchanged between treatments, the renal and secretion clearances and the excretion ratio of cefonicid were reduced by about 40% in the presence of AII (excretion ratios, 10.3 without AII versus 6.03 with AII). These results suggest that the altered clearance parameters of cefonicid are the result of a flow-induced change in the intrinsic secretory transport of the drug. PMID- 1622173 TI - Addition of rifampin to combination antibiotic therapy for Pseudomonas aeruginosa bacteremia: prospective trial using the Zelen protocol. AB - A multicenter, prospective randomized trial was conducted to determine if the addition of rifampin to a combination therapy of an antipseudomonal beta-lactam agent and aminoglycoside improves the outcome of patients with Pseudomonas aeruginosa bacteremia. The Zelen protocol for randomized-consent design was used. Consent was sought only from patients randomized to the experimental therapy (rifampin+). If the experimental therapy was refused, the patient would then receive the standard combination therapy (control); however, when outcome was evaluated, all patients randomized to the rifampin+ group, including those that declined rifampin, were compared with the control group. One hundred twenty-one consecutive hospitalized patients with positive blood cultures for P. aeruginosa were enrolled. Entry was stratified for prior use of empiric antipseudomonal antibiotics, neutropenia, severity of illness, and presence of pneumonia. Fifty eight patients were randomized to receive rifampin (600 mg orally every 8 h for the first 72 h and then every 12 h for a total of 10 days) plus a beta-lactam agent plus an aminoglycoside. Sixty-three received the standard therapy of a beta lactam plus an aminoglycoside agent (control). Bacteriologic cure occurred significantly more frequently in patients randomized to the rifampin+ regimen. Breakthrough or relapsing bacteremias occurred in 2% of the three-drug (rifampin+) group, compared with 14% for the two-drug (standard therapy) group. Despite this favorable trend in bacteriological response, no significant differences in survival were seen for the two treatment groups. Rifamycin derivatives warrant further clinical study as antipseudomonal agents. The Zelen protocol appears well suited for comparative trials of antimicrobial agents. PMID- 1622174 TI - Effect of glycerol monolaurate on bacterial growth and toxin production. AB - Glycerol monolaurate (GML) is a naturally occurring surfactant that has potential use as an additive to tampons and wound dressings to reduce the incidence of certain bacterial toxin-mediated illnesses. In vitro studies were undertaken to evaluate the effect of GML on the growth of and toxin production by potentially pathogenic bacteria. GML inhibited the growth of clinical isolates of group A, B, F, and G streptococci at concentrations of 10 to 20 micrograms/ml. Exotoxin production, including that of pyrogenic exotoxins and hemolysins, was reduced by concentrations of GML that were below those inhibitory for growth as well as growth inhibitory. The growth of Staphylococcus aureus strains from patients with toxic shock syndrome and scalded skin syndrome was inhibited or delayed in the presence of 100 to 300 micrograms of GML per ml. Growth inhibition by GML could be overcome by the production of lipase. S. aureus elaboration of hemolysin, toxic shock syndrome toxin 1, and exfoliative toxin A was inhibited at GML concentrations below those necessary to inhibit growth. Results similar to those for S. aureus were obtained in tests of S. hominis. Escherichia coli growth and Salmonella minnesota growth were unaffected by GML, but an S. minnesota Re mutant was susceptible to growth-inhibitory activity. Endotoxin release into the medium from E. coli cells was also unaffected by GML, but the release or activity of E. coli hemolysin was increased by GML. Streptococcal pyrogenic endotoxin A production by an E. coli clone was not affectd by GML. These studies indicate that GML is effective in blocking or delaying the production of exotoxins by pathogenic gram-positive bacteria. PMID- 1622175 TI - Fleroxacin pharmacokinetics in patients with liver cirrhosis. AB - In this open-label study, the disposition of fleroxacin in liver disease in 12 healthy male volunteers, 6 male cirrhotics without ascites (group A), and 6 male cirrhotics with ascites (group B) was evaluated. Fleroxacin (400 mg) was administered orally and intravenously to each subject in a random crossover fashion. Fleroxacin was completely absorbed and achieved similar peak concentrations in plasma in all three study groups (P greater than 0.05). The volume of distribution exceeded 1 liter/kg in healthy controls and was not affected by liver impairment (P greater than 0.05). Only group B demonstrated differences in the pharmacokinetic parameters evaluated: the systemic and renal clearances of fleroxacin and the renal clearances and clearances of the two major metabolites of fleroxacin formed, N-demethyl fleroxacin and fleroxacin N-oxide, were significantly lower and the half-lives of the parent drug and its metabolites were significantly longer in group B than in healthy controls and group A (P less than 0.05). The elimination of the two metabolites appeared to be formation rate limited in all three study groups. It was concluded from this study that a 50% reduction in the fleroxacin maintenance dose in patients with liver disease appears justified only in patients with ascites. However, no change in the fleroxacin loading dose is needed in patients with compromised liver function. PMID- 1622176 TI - Inducible expression of ribosomal clindamycin resistance in Bacteroides vulgatus. AB - The abilities of erythromycin and clindamycin to act as inducers of clindamycin resistance in the strain Bacteroides vulgatus RYC18F6 is evaluated in vivo (efficiency of plating of inhibitory clindamycin concentrations) and in vitro [efficiency of poly(U)-directed polypeptide synthesis by ribosomes]. Uninduced cells failed to grow during the first 72 h, even at a very low clindamycin concentration (0.1 microgram/ml); after induction with erythromycin or clindamycin, cells were able to form colonies at 32 micrograms/ml after 48 h. The in vitro polymerization test with B. vulgatus RYC18F6 ribosomes (S-30 extract) showed that ribosomes from uninduced cells were fully sensitive to the inhibitory effect of clindamycin. Ribosomes obtained from erythromycin- or clindamycin induced cells presented a reduced sensitivity to clindamycin inhibition. These results show that resistance to clindamycin in B. vulgatus RYC18F6 is an inducible phenomenon involving a ribosomal modification, probably similar to that previously described for gram-positive bacteria. PMID- 1622177 TI - Effects of immunoglobulin G and low-dose amphotericin B on Candida albicans infections in burned mice. AB - Candidiasis causes serious problems for compromised hosts. Effective treatments for Candida albicans infections are few. To see if immunoglobulin (Ig) therapy could be beneficial, burn-immunocompromised mice were treated intravenously with 2.5 mg of five different IgG preparations 48 h postburn and post-C. albicans challenge. Despite up to fourfold differences in titer (1:1,600 to 1:6,400) to C. albicans, all preparations improved 10-day survival about 30% (P less than 0.0001). Treatment with a low dose of amphotericin B (AmB; 0.09 mg/kg of body weight) intravenously 24 and 48 h after burn and challenge improved survival 9 to 45% (P less than 0.0001). Treatment with a low dose of AmB plus IgG showed the same results as treatment with AmB alone and better results than treatment with IgG alone. Quantitative renal cultures from burned mice treated with AmB plus one IgG preparation, Sandoglobulin, showed that C. albicans counts decreased in sham treated mice from 7.21 +/- 0.15 log10 CFU/g (mean +/- standard error of the mean) to 5.31 +/- 0.34, which was significantly less than counts with AmB (6.11 +/- 0.35) or Sandoglobulin (6.39 +/- 0.18) treatment alone. We conclude that (i) by using decreases in mortality and in renal fungal load as end points, treatment with IgG preparations alone or with a low dose of AmB alone protected burn immunocompromised mice from candidiasis; (ii) though AmB plus one IgG preparation significantly decreased renal fungal load, the combination did not significantly decrease mortality beyond that found with AmB alone; and (iii) survival data did not correlate with IgG titers to C. albicans. PMID- 1622178 TI - Rapid and sensitive assay for fluconazole which uses gas chromatography with electron capture detection. AB - Fluconazole, an orally active antifungal agent, has been shown to be clinically beneficial for maintenance therapy of cryptococcal meningitis. A sensitive gas liquid chromatographic assay with electron capture detection, which required only a single extraction step and precluded any pretreatment of the chromatographic column, was developed for fluconazole. The assay was linear from 0.1 to 20 micrograms/ml, with a correlation coefficient of 0.999. The intraassay and interassay coefficients of variation were less than 9%. The measured values on average were within 8% of the target values. The extraction recoveries ranged from 87 to 106%. Steady-state plasma fluconazole levels (mean +/- standard deviation) in three AIDS patients with cryptococcal meningitis receiving 200 mg of fluconazole per day ranged from 8.95 +/- 1.32 to 11.41 +/- 0.63 micrograms/ml and were within the expected range for this dosing rate, on the basis of previous studies. The ratio of fluconazole concentration in cerebrospinal fluid to fluconazole concentration in plasma in one patient receiving 400 mg/day was 0.73 at steady state and was consistent with published reports. PMID- 1622179 TI - Penetration of fleroxacin and ciprofloxacin into skin blister fluid: a comparative study. AB - The penetration of multiple-dose concentrations of oral fleroxacin (400 mg every 24 h) and ciprofloxacin (500 mg every 12 h) into skin blister fluid in 12 healthy volunteers was determined in a randomized crossover study. Serum, blister fluid, and paper disk samples were analyzed by large-plate microbiologic assay. The mean areas under the concentration-time curve (AUC) for serum were 88.6 and 18.2 micrograms.h/ml/70 kg for fleroxacin and ciprofloxacin, respectively. The mean AUC for blister fluid and paper disks were 71.2 and 15.0 micrograms.h/ml/70 kg and 77.8 and 15.4 micrograms.h/ml/70 kg for fleroxacin and ciprofloxacin, respectively. Calculated penetration into interstitial fluid ranged from 74 to 92% for fleroxacin and 56 to 96% for ciprofloxacin; penetration was calculated by using the ratio of maximum drug concentration or AUC in blister fluid and paper disks to maximum drug concentration or AUC in serum. There was no significant difference between fleroxacin and ciprofloxacin in the percent penetration into skin blister fluid. PMID- 1622180 TI - Characterization of penicillin-binding protein 2 of Staphylococcus aureus: deacylation reaction and identification of two penicillin-binding peptides. AB - Penicillin-binding protein (PBP) 2 is the major PBP of five that have been identified in susceptible strains of Staphylococcus aureus. Beta-lactam antibiotic binding to PBP 2 is important for the antibacterial effect. Antibiotic binding to PBP 2 in strain 209P was examined with sodium dodecyl sulfate polyacrylamide gel electrophoresis in competition assays using [3H]penicillin as the radiolabel. Clavulanic acid, which is specifically bound by PBP 2, and cefaclor, which is specific for PBP 3, were studied. Cefaclor, which alone appeared not to bind PBP 2, in combination inhibited PBP 2 binding of clavulanic acid. By varying the temperature during radiolabeling with [3H]penicillin in cefaclor competition assays and in direct radiolabeling assays with [3H]cefaclor, it was shown that cefaclor was bound by PBP 2 with high affinity (50% inhibitory concentration, less than or equal to 0.1 microgram/ml) and that the apparent low affinity binding (50% inhibitory concentration, greater than 10 micrograms/ml) in competition assays performed at 37 degrees C was due to rapid deacylation. Two penicillin-binding peptides of PBP 2 also were identified in fluorographs of PBPs separated by nonequilibrium pH gradient gel and two-dimensional electrophoresis. Rapid deacylation for some antibiotics and the presence of two penicillin-binding peptides are two properties of PBP 2 that should be considered when correlating results of binding assays with effects of beta-lactam antibiotics on S. aureus. PMID- 1622181 TI - Resistance of Peptostreptococcus spp. to macrolides and lincosamides: inducible and constitutive phenotypes. AB - The activities of erythromycin and clindamycin against 350 Peptostreptococcus strains were studied during a 5-year period (1986 to 1991). In 5.1% of the Peptostreptococcus strains, which presented dissociated resistance (clindamycin MIC, less than or equal to 1 microgram/ml; erythromycin MIC, greater than 8 micrograms/ml), evidence of inducible macrolide-lincosamide resistance was shown. A total of 17.7% of the strains presented a constitutive phenotype; the clindamycin and erythromycin MICs for these strains were greater than 8 micrograms/ml. PMID- 1622182 TI - Lack of pharmacokinetic interaction between intravenous 2',3'-dideoxyinosine and 3'-azido-3'-deoxythymidine in rats. AB - We investigated the pharmacokinetic interaction between 3'-azido-3' deoxythymidine (AZT) and 2',3'-dideoxyinosine (ddI), given to rats by intravenous injection. For both compounds, the clearances, terminal half-lives, and fractions of the dose excreted unchanged in urine were not altered by the other drug (P greater than 0.05), indicating no pharmacokinetic interaction between the two drugs. PMID- 1622183 TI - Susceptibility of Xanthomonas maltophilia to six quinolones and study of outer membrane proteins in resistant mutants selected in vitro. AB - The in vitro susceptibilities of 75 clinical isolates of Xanthomonas maltophilia to nalidixic acid, five fluoroquinolones, latamoxef, and doxycycline were determined. Spontaneous mutants were selected, at a frequency of about 10(-5) to 10(-7) from four strains by culturing the strains in the presence of each quinolone. Selection in the presence of nalidixic acid provided mutants that were either resistant only to that compound or that exhibited cross-resistance to all the fluoroquinolones tested. Cross-resistance was always observed for mutants selected on any of the five fluoroquinolones. It was always associated with chloramphenicol resistance and, frequently, with doxycycline resistance. The electrophoretic alterations of the outer membrane proteins of the mutants suggest that different mechanisms may be involved in quinolone resistance in X. maltophilia. PMID- 1622184 TI - Distribution of ciprofloxacin in ascitic fluid following administration of a single oral dose of 750 milligrams. AB - The penetration of ciprofloxacin into the ascitic fluid of eight patients was studied. Serum and ascitic fluid samples were obtained before and at 1, 2, 3, 6, and 12 h following administration of a single oral dose of 750 mg. Peak levels (mean +/- standard deviation) were 4.0 +/- 0.7 micrograms/ml in serum and 2.6 +/- 0.6 micrograms/ml in ascitic fluid; the areas under the curve (0 to 12 h) were 29.1 +/- 6.5 micrograms.h/ml in serum and 20.7 +/- 5.0 micrograms.h/ml in ascitic fluid. The concentrations that were achieved are well above the MICs of ciprofloxacin for the members of the family Enterobacteriaceae that cause spontaneous bacterial peritonitis. PMID- 1622185 TI - Variation in the pharmacokinetics of gentamicin and tobramycin in patients with pleural effusions and hypoalbuminemia. AB - The pharmacokinetic parameters of gentamicin and tobramycin were evaluated and compared for 260 patients with pleural effusions and 1,049 patients without pleural effusions by chest radiograph. Pharmacokinetic data were collected prospectively and analyzed by using our aminoglycoside data base. Univariate analysis revealed that the patients with pleural effusions demonstrated significantly lower serum albumin concentrations, greater aminoglycoside volumes of distribution, longer elimination half-lives, and lower peak and higher trough concentrations in serum than the patients without pleural effusions. Patients with pleural effusions were significantly older and had lower total body weight. Stepwise multiple linear regression analysis revealed that lower total body weight and serum albumin concentration, presence of pleural effusion, and greater age were associated with significantly greater volumes of distribution. Calculated creatinine clearance, age, total body weight, and shock were associated with reduced aminoglycoside clearance in these patients. PMID- 1622186 TI - In vitro activity of E1040 against imipenem-resistant Pseudomonas aeruginosa strains. AB - E1040 showed the most potent activity (MIC for 90% of strains, 6.25 micrograms/ml) among beta-lactams tested against 70 strains of imipenem-resistant Pseudomonas aeruginosa. Two strains showed high-level resistance to E1040; one strain produced a type II oxyiminocephalosporin-hydrolyzing beta-lactamase (group 3), and the other produced an enzyme similar to a type II penicillinase (OXA-1). Both beta-lactamases contributed to resistance to E1040. PMID- 1622187 TI - Absolute bioavailability of cefprozil after oral administration in beagles. AB - The absolute bioavailability of cefprozil, a new oral cephalosporin, in four beagles was evaluated. In this two-way crossover study, each dog received a 125 mg dose of cefprozil either as an oral aqueous solution or as a 15-min intravenous infusion. A high-performance liquid chromatographic assay with UV detection was employed for the determination of cefprozil concentrations in plasma and urine. Key pharmacokinetic parameters were calculated by noncompartmental methods. Cefprozil was well absorbed after oral administration, and peak concentrations of 17.6 to 26.6 micrograms/ml were attained at 60 min after drug administration. The apparent elimination half-life of cefprozil was about 70 min. The renal clearance was about 60% of total body clearance and is suggestive of significant nonrenal clearance. The absolute bioavailability of cefprozil ranged from 67.1 to 79.1% in the dogs. PMID- 1622188 TI - Use of high-dose fluconazole as salvage therapy for cryptococcal meningitis in patients with AIDS. AB - Eight patients with AIDS were treated orally with 800 mg of fluconazole daily for cryptococcal meningitis for a mean duration of 4.5 months. Previous antifungal treatment had failed for all of the patients. No major toxicity was observed. Three patients died from cryptococcal infection. High-dose fluconazole may be effective salvage therapy for cryptococcal meningitis. PMID- 1622189 TI - Let's give the feds credit for useable, credible clinical practice guidelines. PMID- 1622190 TI - Proposed recommended practices. Universal precautions. PMID- 1622191 TI - Issues regarding parents in the operating room during their children's care. AB - The presence of parents in the operating room does have possible legal ramifications. Taking an upset child from a parent's arms, however, is not a positive situation either. Perioperative nurses should not automatically weigh legal implications more heavily than the patient benefit that may be derived from the presence of parents. Whether parents should or should not be allowed to accompany their children into the operating room should be a carefully considered institutional policy. PMID- 1622192 TI - Symposium offers nurses from around the country valuable information, opportunities to network with colleagues. May 7 to 9, 1992. PMID- 1622193 TI - States address a variety of health care issues. PMID- 1622194 TI - Cancer of the penis. Perioperative interventions. PMID- 1622195 TI - Number of new AIDS cases increasing. PMID- 1622196 TI - Kidney cancer. An overview of the disease, treatment. PMID- 1622197 TI - Cytoreductive surgery and intraperitoneal chemotherapy. Treatment for peritoneal carcinomatosis. PMID- 1622198 TI - Head and neck cancer. An overview for the perioperative nurse. PMID- 1622199 TI - Getting students into the OR is only half the battle. PMID- 1622200 TI - Documenting nursing process in the perioperative setting. Continuity of care, patient evaluation. AB - Using our Perioperative Nursing Process form in addition to intraoperative and PACU flow sheets allows us to document the nursing process in a manner that satisfies the goals for documentation established by our committee. Because we place all forms in the patients' medical records, they are available for review by the JCAHO to prove that we comply with their standards and the standards of AORN and ANA. The nurses have been satisfied with the documentation system because it can be used efficiently and does not require redundant documentation as the patient transfers into each perioperative area. PMID- 1622201 TI - Hemicellulose bioconversion to polyanionic heteropolysaccharides. AB - Anionic polysaccharides, traditionally obtained from plant or algal sources, have a variety of commercial uses. Such gums from microorganisms have received increased recent interest. We have initiated a program to investigate the bioconversion of pentosans to rheologically useful anionic extracellular polysaccharides (AEPS). A number of earlier-described species, including Cryptococcus laurentii, Klebsiella pneumoniae, Arthrobacter viscosus, and Pseudomonas ATCC 31260, appear to have potential in this regard. These organisms can individually convert either xylose, enzymatic oligomeric hemicellulose digests, dilute mineral acid hemicellulose ("TVA") hydrolysates, or a five monosaccharide mixture simulating sulfite process liquors to AEPS. The formation parameters, compositions, mol-wt distributions, and the intrinsic viscosities of these purified AEPS are exemplified. Substitution of pentose as the major substrate for glucose can result in changes in mol-wt distribution or in the percentage of noncarbohydrate substituents in some AEPS. Pursuit of these observations may lead to interesting structure-property relationships and toward rheological applications for pentosan-derived AEPS. PMID- 1622202 TI - Enhancement of 1,3-propanediol production by cofermentation in Escherichia coli expressing Klebsiella pneumoniae dha regulon genes. AB - 1,3-Propanediol (1,3-PD) is an intermediate in chemical and polymer synthesis. We have previously expressed the genes of a biochemical pathway responsible for 1,3 PD production, the dha regulon of Klebsiella pneumoniae, in Escherichia coli. An analysis of the maximum theoretical yield of 1,3-PD from glycerol indicates that the yield can be improved by the cofermentation of sugars, provided that kinetic constraints are overcome. The yield of 1,3-PD from glycerol was improved from 0.46 mol/mol with glycerol alone to 0.63 mol/mol with glucose cofermentation and 0.55 mol/mol with xylose cofermentation. The engineered E. coli also provides a model system for the study of metabolic pathway engineering. PMID- 1622203 TI - Effect of acetic acid on xylose conversion to ethanol by genetically engineered E. coli. AB - Efficient utilization of the pentosan fraction of hemicellulose from lignocellulosic feedstocks offers an opportunity to increase the yield and to reduce the cost of producing fuel ethanol. During prehydrolysis (acid hydrolysis or autohydrolysis of hemicellulose), acetic acid is formed as a consequence of the deacetylation of the acetylated moiety of hemicellulose. Recombinant Escherichia coli B (ATCC 11303), carrying the plasmid pLO1297 with pyruvate decarboxylase and alcohol dehydrogenase II genes from Zymomonas mobilis (CP4), converts xylose to ethanol with a product yield that approaches theoretical maximum. Although other pentose-utilizing microorganisms are inhibited by acetic acid, the recombinant E. coli displays a high tolerance for acetic acid. In xylose fermentations with a synthetic medium (Luria broth), where the pH was controlled at 7, neither yield nor productivity was affected by the addition of 10.7 g/L acetic acid. Nutrient-supplemented, hardwood (aspen) hemicellulose hydrolysate (40.7 g/L xylose) was completely fermented to ethanol (16.3 g/L) in 98 h. When the acetic acid concentration was reduced from 5.6 to 0.8 g/L, the fermentation time decreased to 58 h. Overliming, with Ca(OH)2 to pH 10, followed by neutralization to pH 7 with sulfuric acid and removal of insolubles, resulted in a twofold increase in volumetric productivity. The maximum productivity was 0.93 g/L/h. The xylose-to-ethanol conversion efficiency and productivity in Ca(OH)2-treated hardwood prehydrolysate, fortified with only mineral salts, were 94% and 0.26 g/L/h, respectively. The recombinant E. coli exhibits a xylose-to ethanol conversion efficiency that is superior to that of other pentose-utilizing yeasts currently being investigated for the production of fuel ethanol from lignocellulosic materials. PMID- 1622204 TI - Purification and characterization of a xylanase from the thermophilic ascomycete Thelavia terrestris 255B. AB - Thielavia terrestris 255B, a thermophilic ascomycete, produced two major forms of xylanase with pIs of 4.6 (xylanase I) and 6.1 (xylanase II). The latter enzyme could be purified to greater than 99% homogeneity using anion-exchange chromatography and gel filtration. Xylanase II had a mol wt of 25.7 kDa (SDS PAGE) and a pH and a temperature optimum of 3.6-4.0 and 60-65 degrees C, respectively. The ratio of the enzyme's activity against xylan and carboxymethylcellulose was 500-1000 to 1, indicating a possible application of this enzyme in biobleaching processes. The amino acid sequence of this protein is being determined, and initial data suggest that the enzyme belongs to a group of low-mol wt xylanases that have been isolated from both bacteria and fungi. PMID- 1622205 TI - Properties of the seed gum of Strypnodendron barbatiman (barbatimao). PMID- 1622207 TI - Isolation and characterization of an acidophilic, heterotrophic bacterium capable of oxidizing ferrous iron. AB - A heterotrophic bacterium, isolated from an acidic stream in a disused pyrite mine which contained copious growths of "acid streamers," displayed characteristics which differentiated it from previously described mesophilic acidophiles. The isolate was obligately acidophilic, with a pH range of 2.0 to 4.4 and an optimum pH of 3.0. The bacterium was unable to fix carbon dioxide but oxidized ferrous iron, although at a slower rate than either Thiobacillus ferrooxidans or Leptospirillum ferrooxidans. Elemental sulfur and manganese(II) were not oxidized. In liquid media, the isolate produced macroscopic streamerlike growths. Microscopic examination revealed that the bacterium formed long (greater than 100 microns) filaments which tended to disintegrate during later growth stages, producing single, motile cells and small filaments. The isolate did not appear to utilize the energy from ferrous iron oxidation. Both iron (ferrous or ferric) and an organic substrate were necessary to promote growth. The isolate displayed a lower tolerance to heavy metals than other iron-oxidizing acidophiles, and growth was inhibited by exposure to light. There was evidence of extracellular sheath production by the isolate. In this and some other respects, the isolate resembles members of the Sphaerotilus-Leptothrix group of filamentous bacteria. The guanine-plus-cytosine content of the isolate was 62 mol%, which is less than that recorded for Sphaerotilus-Leptothrix spp. and greater than those of L. ferrooxidans and most T. ferrooxidans isolates. PMID- 1622206 TI - Purification and characterization of a new bacteriocin isolated from a Carnobacterium sp. AB - A bacteriocin-producing Carnobacterium sp. was isolated from fish. The bacteriocin, termed carnocin UI49, was purified to homogeneity by a four-step purification procedure, including hydrophobic interaction chromatography and reverse-phase chromatography. Carnocin UI49 has a bactericidal mode of action. It was shown to be heat tolerant and stable between pH 2 and 8. At pH above 8, carnocin UI49 was rapidly inactivated. Amino acid analysis revealed a composition of about 35 to 37 amino acids in addition to an unidentified peak which migrates at the position of lanthionine. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis suggests a molecular weight of about 4,500 to 5,000. Mass spectrometry gave a molecular weight of 4,635, which is about 1,000 larger than that calculated from the amino acid analysis data. Performic acid oxidation of carnocin UI49, followed by amino acid hydrolysis, revealed the presence of cysteic acid. The sequence of the first seven amino acid residues was determined to be N-Gly-Ser-Glu-Ile-Gln-Pro-Arg. After the seventh amino acid, carnocin UI49 was not available for further Edman degradation. The results suggest that carnocin UI49 belongs to the class of bacteriocins termed lantibiotics. PMID- 1622208 TI - Lactococcus lactis release from calcium alginate beads. AB - Cell release during milk fermentation by Lactococcus lactis immobilized in calcium alginate beads was examined. Numbers of free cells in the milk gradually increased from 1 x 10(6) to 3 x 10(7) CFU/ml upon successive reutilization of the beads. Rinsing the beads between fermentations did not influence the numbers of free cells in the milk. Cell release was not affected by initial cell density within the beads or by alginate concentration, although higher acidification rates were achieved with increased cell loading. Coating alginate beads with poly L-lysine (PLL) did not significantly reduce the release of cells during five consecutive fermentations. A double coating of PLL and alginate reduced cell release by a factor of approximately 50. However, acidification of milk with beads having the PLL-alginate coating was slower than that with uncoated beads. Immersing the beads in ethanol to kill cells on the periphery reduced cell release, but acidification activity was maintained. Dipping the beads in aluminum nitrate or a hot CaCl2 solution was not as effective as dipping them in ethanol. Ethanol treatment or heating of the beads appears to be a promising method for maintaining acidification activity while minimizing viable cell release due to loosely entrapped cells near the surface of the alginate beads. PMID- 1622209 TI - Pathovar-specific requirement for the Pseudomonas syringae lemA gene in disease lesion formation. AB - The lemA gene is conserved among strains and pathovars of Pseudomonas syringae. In P. syringae pv. syringae B728a, a causal agent of bacterial brown spot disese of bean, the lemA gene is required for lesion formation on leaves and pods. Using lemA-containing DNA as a probe, we determined that 80 P. syringae pv. syringae strains isolated from bean leaves could be grouped into seven classes based on restriction fragment length polymorphism. Marker exchange mutagenesis showed that the lemA gene was required for lesion formation by representative strains from each restriction fragment length polymorphism class. Hybridization to the lemA locus was detected within six different P. syringae pathovars and within Pseudomonas aeruginosa. Interestingly, a lemA homolog was present and functional within the nonpathogenic strain P. syringae Cit7. We cloned a lemA homolog from a genomic library of P. syringae pv. phaseolicola NPS3121, a causal agent of halo blight of bean, that restored lesion formation to a P. syringae pv. syringae lemA mutant. However, a lemA mutant P. syringae pv. phaseolicola strain retained the ability to produce halo blight disease symptoms on bean plants. Therefore, the lemA gene played an essential role in disease lesion formation by P. syringae pv. syringae isolates, but was not required for pathogenicity of a P. syringae pv. phaseolicola strain. PMID- 1622210 TI - Purification and characterization of two alpha-L-arabinofuranosidases from Streptomyces diastaticus. AB - A nonsporulating strain of Streptomyces diastaticus producing alpha-L arabinofuranosidase activity (EC 3.2-1.55) was isolated from soil. Two alpha-L arabinosidases were purified by ion-exchange chromatography and chromatofocusing. The enzymes had molecular weights of 38,000 (C1) and 60,000 (C2) and pIs of 8.8 and 8.3, respectively. The optimum pH range of activity for both enzymes was between 4 and 7. The apparent Km values with p-nitrophenyl arabinofuranoside as the substrate were 10 mM (C1) and 12.5 mM (C2). C1 retained 50% of its activity after 8 h of incubation at 25 degrees C, while C2 retained 80% activity. After 3 h of incubation at 50 degrees C, C1 lost 90% of its initial activity while C2 lost only 40%. The purified enzymes hydrolyzed p-nitrophenyl alpha-L arabinofuranoside and liberated arabinose from arabinoxylan and from a debranched beta-1,5-arabinan. PMID- 1622211 TI - Production of citric and oxalic acids and solubilization of calcium phosphate by Penicillium bilaii. AB - An isolate of Penicillium bilaii previously reported to solubilize mineral phosphates and enhance plant uptake of phosphate was studied. Using agar media with calcium phosphate and the pH indicator alizarin red S, the influence of the medium composition on phosphate solubility and medium acidification was recorded. The major acidic metabolites produced by P. bilaii in a sucrose nitrate liquid medium were found to be oxalic acid and citric acid. Citric acid production was promoted under nitrogen-limited conditions, while oxalic acid production was promoted under carbon-limited conditions. Citric acid was produced in both growth and stationary phases, but oxalic acid production occurred only in stationary phase. When submerged cultures which normally produce acid were induced to sporulate, the culture medium shifted toward alkaline rather than acid reaction with growth. PMID- 1622212 TI - Effect of inoculant strain and organic matter content on kinetics of 2,4 dichlorophenoxyacetic acid degradation in soil. AB - We monitored rates of degradation of soluble and sorbed 2,4-dichlorophenoxyacetic acid (2,4-D) in low-organic-matter soil at field capacity amended with 1, 10, or 100 micrograms of 2,4-D per g of wet soil and inoculated with one of two bacterial strains (MI and 155) with similar maximum growth rates (mu max) but significantly different half-saturation growth constants (Ks). Concentrations of soluble 2,4-D were determined by analyzing samples of pore water pressed from soil, and concentrations of sorbed 2,4-D were determined by solvent extraction. Between 65 and 75% of the total 2,4-D was present in the soluble phase at equilibrium, resulting in soil solution concentrations of ca. 8, 60, and 600 micrograms of 2,4-D per ml, respectively. Soluble 2,4-D was metabolized preferentially; this was followed by degradation of both sorbed (after desorption) and soluble 2,4-D. Rates of degradation were comparable for the two strains at soil concentrations of 10 and 100 micrograms of 2,4-D per g; however, at 1 microgram/g of soil, 2,4-D was metabolized more rapidly by the strain with the lower Ks value (strain MI). We also monitored rates of biodegradation of soluble and sorbed 2,4-D in high-organic-matter soil at field capacity amended with 100 micrograms of 2,4-D per g of wet soil and inoculated with the low-Ks strain (strain MI). Ten percent of total 2,4-D was present in the soluble phase, resulting in a soil solution concentration of ca. 30 micrograms of 2,4-D per ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1622213 TI - Modelling of mixed chemostat cultures of an aerobic bacterium, Comamonas testosteroni, and an anaerobic bacterium, Veillonella alcalescens: comparison with experimental data. AB - A mathematical model of mixed chemostat cultures of the obligately aerobic bacterium Comamonas testosteroni and the anaerobic bacterium Veillonella alcalescens grown under dual limitation of L-lactate and oxygen was constructed. The model was based on Michaelis-Menten-type kinetics for the consumption of substrates, with noncompetitive inhibition of V. alcalescens by O2. The growth characteristics of the aerobic and anaerobic organisms were determined experimentally with pure cultures of the individual species in (oxygen-limited) chemostats. Using these pure-culture data in the model of the mixed culture resulted in a good description of the actual mixed cultures of the two bacteria. In the actual mixed-culture experiments, coexistence of the two species occurred only when the cultures were oxygen limited. With increasing oxygen supply (the actual oxygen concentration in the culture remaining at less than 0.2 microM), the biomass of C. testosteroni increased, whereas that of V. alcalescens decreased. Apparently, C. testosteroni protected V. alcalescens from inhibition by oxygen by maintaining sufficiently low oxygen concentrations. The model calculations indicated that competition between the aerobic and the anaerobic bacterium for common substrates (L-lactate and oxygen) occurred and that the anaerobe was the better competitor. Analysis of the culture fluid indicated that C. testosteroni grew primarily at the expense of the fermentation products of V. alcalescens, i.e., propionate and acetate. The model further indicated that with different values of several growth parameters (e.g., substrate affinity and/or inhibition constants), the affinity of the aerobic organism for oxygen and the sensitivity of the anaerobic organism for oxygen were the most important properties determining the coexistence of these two physiologically different types of bacteria. PMID- 1622214 TI - Characterization of two nisin-producing Lactococcus lactis subsp. lactis strains isolated from a commercial sauerkraut fermentation. AB - Two Lactococcus lactis subsp. lactis strains, NCK400 and LJH80, isolated from a commercial sauerkraut fermentation were shown to produce nisin. LJH80 was morphologically unstable and gave rise to two stable, nisin-producing (Nip+) derivatives, NCK318-2 and NCK318-3. NCK400 and derivatives of LJH80 exhibited identical morphological and metabolic characteristics, but could be distinguished on the basis of plasmid profiles and genomic hybridization patterns to a DNA probe specific for the iso-ISS1 element, IS946. NCK318-2 and NCK318-3 harbored two and three plasmids, respectively, which hybridized with IS946. Plasmid DNA was not detected in NCK400, and DNA from this strain failed to hybridize with IS946. Despite the absence of detectable plasmid DNA in NCK400, nisin-negative derivatives (NCK402 and NCK403) were isolated after repeated transfer in broth at 37 degrees C. Nisin-negative derivatives concurrently lost the ability to ferment sucrose and became sensitive to nisin. A 4-kbp HindIII fragment containing the structural gene for nisin (spaN), cloned from L. lactis subsp. lactis ATCC 11454, was used to probe genomic DNA of NCK318-2, NCK318-3, NCK400, and NCK402 digested with EcoRI or HindIII. The spaN probe hybridized to an 8.8-kbp EcoRI fragment and a 10-kbp HindIII fragment in the Nip+ sauerkraut isolates, but did not hybridize to the Nip- derivative, NCK402. A different hybridization pattern was observed when the same probe was used against Nip+ L. lactis subsp. lactis ATCC 11454 and ATCC 7962. These phenotypic and genetic data confirmed that unique Nip+ L. lactis subsp. lactis strains were isolated from fermenting sauerkraut. PMID- 1622215 TI - Novel paired starter culture system for sauerkraut, consisting of a nisin resistant Leuconostoc mesenteroides strain and a nisin-producing Lactococcus lactis strain. AB - Nisin-resistant Leuconostoc mesenteroides NCK293 and nisin-producing Lactococcus lactis subsp. lactis NCK401 were evaluated separately and in combination for growth and nisin production in a model sauerkraut fermentation. Strains were genetically marked and selectively enumerated by using antibiotic-containing media. The growth and survival of L. mesenteroides were similar in the presence and absence of Lactococcus lactis subsp. lactis. The growth of Lactococcus lactis subsp. lactis was not inhibited, although the maximum cell density was reduced and the population decline was more pronounced in the presence of L. mesenteroides. Nisin was detected within 24 h, and levels were relatively constant over the 12-day test period. The maximum cell populations and nisin level achieved could be altered by changing the initial cell ratios of L. mesenteroides and lactococcus lactis subsp. lactis. Isogenic nisin-producing and nisin-negative Lactococcus lactis subsp. lactis derivatives were used in combination with nisin-resistant L. mesenteroides to demonstrate that nisin levels produced in mixed culture were sufficient to retard the onset of the growth of nisin-sensitive, homofermentative Lactobacillus plantarum ATCC 14917. PMID- 1622216 TI - Production of manganic chelates by laccase from the lignin-degrading fungus Trametes (Coriolus) versicolor. AB - Many ligninolytic basidiomycete fungi have been shown to secrete a group of peroxidase isozymes whose sole function appears to be the peroxide-dependent oxidation of manganous [Mn(II)] to manganic [Mn(III)] ions. Manganic chelates and these Mn peroxidases have been implicated as central to the degradation of various natural and synthetic lignins and lignin-containing effluents by white rot (ligninolytic) fungi. Another group of enzymes, the laccases, are commonly secreted by wood-rotting fungi, but are generally regarded as being able to oxidize (and usually polymerize) only phenolic substrates. In this report it is shown that in the presence of appropriate oxidizable phenolic accessory substances or primary substrates, a variety of laccases and peroxidases catalyzing one-electron oxidations can also produce Mn(III) chelates from Mn(II). PMID- 1622217 TI - Bacterial migration along solid surfaces. AB - An in vitro system was developed to study the migration of uropathogenic Escherichia coli strains. In this system an aqueous agar gel is placed against a solid surface, allowing the bacteria to migrate along the gel/solid surface interface. Bacterial strains as well as solid surfaces were characterized by means of water contact angle and zeta potential measurements. When glass was used as the solid surface, significantly different migration times for the strains investigated were observed. Relationships among the observed migration times of six strains, their contact angles, and their zeta potentials were found. Relatively hydrophobic strains exhibited migration times shorter than those of hydrophilic strains. For highly negatively charged strains shorter migration times were found than were found for less negatively charged strains. When the fastest-migrating strain with respect to glass was allowed to migrate along solid surfaces differing in hydrophobicity and charge, no differences in migration times were found. Our findings indicate that strategies to prevent catheter associated bacteriuria should be based on inhibition of bacterial growth rather than on modifying the physicochemical character of the catheter surface. PMID- 1622218 TI - Persistence of Vibrio vulnificus in tissues of Gulf Coast oysters, Crassostrea virginica, exposed to seawater disinfected with UV light. AB - Vibrio vulnificus is an estuarine bacterium which can cause opportunistic infections in humans consuming raw Gulf Coast oysters, Crassostrea virginica. Although V. vulnificus is known as a ubiquitous organism in the Gulf of Mexico, its ecological relationship with C. virginica has not been adequately defined. The objective of the present study was to test the hypothesis that V. vulnificus is a persistent microbial flora of oysters and unamenable to traditional methods of controlled purification, such as UV light depuration. Experimental depuration systems consisted of aquaria containing temperature-controlled seawater treated with UV light and 0.2-microns-pore-size filtration. V. vulnificus was enumerated in seawater, oyster shell biofilms, homogenates of whole oyster meats, and tissues including the hemolymph, digestive region, gills, mantle, and adductor muscle. Results showed that depuration systems conducted at temperatures greater than 23 degrees C caused V. vulnificus counts to increase in oysters, especially in the hemolymph, adductor muscle, and mantle. Throughout the process, depuration water contained high concentrations of V. vulnificus, indicating that the disinfection properties of UV radiation and 0.2-microns-pore-size filtration were less than the rate at which V. vulnificus was released into seawater. Approximately 10(5) to 10(6) V. vulnificus organisms were released from each oyster per hour, with 0.05 to 35% originating from shell surfaces. These surfaces contained greater than 10(3) V. vulnificus organisms per cm2. In contrast, when depuration seawater was maintained at 15 degrees C, V. vulnificus was not detected in seawater and multiplication in oyster tissues was inhibited. PMID- 1622219 TI - Enhanced heterologous gene expression in novel rpoH mutants of Escherichia coli. AB - Extragenic temperature-resistant suppressor mutants of an rpoD800 derivative of Escherichia coli W3110 were selected at 43.5 degrees C. Two of the mutants were shown to have a phenotype of enhanced accumulation of heterologous proteins. Genetic mapping of the two mutants showed that the mutation conferring temperature resistance resided in the rpoH gene. P1-mediated transduction of the rpoD+ gene into both of the rpoD800 rpoH double mutants resulted in viable rpoH mutants, MON102 and MON105, that retained temperature resistance at 46 degrees C, the maximum growth temperature of W3110. The complete rpoH gene, including the regulatory region, from MON102, MON105, and the parental W3110 was cloned and sequenced. Sequencing results showed that a single C----T transition at nucleotide 802 was present in both MON102 and MON105, resulting in an Arg(CGC)--- Cys(TGC) substitution at amino acid residue 268 (R-268-C; this gene was designated rpoH358). Heterologous protein accumulation levels in both MON102 and MON105, as well as in rpoH358 mutants constructed in previously unmanipulated W3110 and JM101, were assessed and compared with parental W3110 and JM101 levels. Expression studies utilizing the recA or araBAD promoter and the phage T7 gene 10L ribosome-binding site (g10L) showed that increased accumulation levels of a number of representative heterologous proteins (i.e., human or bovine insulin like growth factor-1, bovine insulin-like growth factor-2, prohormone of human atrial natriuretic factor, bovine placental lactogen, and/or bovine prolactin) were obtained in the rpoH358 mutants compared with the levels in the parental W3110 and JM101. The mechanism of enhanced heterologous protein accumulation in MON102 and MON105 was unique compared with those of previously described rpoH mutants. Pulse-chase and Northern (RNA) blot analyses showed that the enhanced accumulation of heterologous proteins was not due to decreased proteolysis but was instead due to increased levels of the respective heterologous mRNAs accompanied by increased synthesis of the respective heterologous proteins. The plasmid copy number remained unaltered. PMID- 1622220 TI - Rapid detection of members of the family Enterobacteriaceae by a monoclonal antibody. AB - Six monoclonal antibodies directed against enterobacteria were produced and characterized. The specificity of one of these antibodies (CX9/15; immunoglobulin G2a) was studied by indirect immunofluorescence against 259 enterobacterial strains and 125 other gram-negative bacteria. All of the enterobacteria were specifically recognized, the only exception being Erwinia chrysanthemi (one strain tested). Bacteria not belonging to members of the family Enterobacteriaceae were not detected, except for Plesiomonas shigelloides (two strains tested), Aeromonas hydrophila (five strains tested), and Aeromonas sobria (one strain tested). This recognition spectrum strongly suggested that CX9/15 recognized the enterobacterial common antigen. By sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot (immunoblot) experiments, the six antienterobacteria antibodies presented similar specificities; they all revealed only one band with an apparent molecular weight of about 20,000 from the crude extract of an enterobacterium. The six monoclonal antibodies, and especially CX9/15, can be used to develop new tests for rapid and specific detection of enterobacteria. PMID- 1622221 TI - Comparison of an in vitro method and an in vivo method of Giardia excystation. AB - An in vitro method and an in vivo method of excystation were compared to determine the most useful method for the retrieval of Giardia duodenalis isolates. Cysts from 11 Giardia strains were used. In vitro excystation produced motile trophozoites in 16 sets, while in vivo excystation produced trophozoites in all of the 21 comparative sets of excystations. Few cultures were lost because of contamination by either method (17% of in vitro-derived trophozoites versus 23% of in vivo-derived trophozoites; P greater than 0.05). Both methods demonstrated comparable isolate retrieval rates (15% of in vitro-derived trophozoites adapting to culture compared with 29% of in vivo-derived trophozoites; P greater than 0.05), although analysis of the strains retrieved showed that two isolates were retrieved from in vitro excystation alone, compared with four from in vivo excystation. Analysis that included results of extra in vivo cultures showed that a total of nine isolates were retrieved by using this type of excystation. Despite the disadvantages of cost and labor, in vivo excystation appears to be more useful than in vitro excystation for isolate retrieval at the present time. PMID- 1622222 TI - Analysis of proteins associated with growth of Bacteroides ovatus on the branched galactomannan guar gum. AB - Bacteroides ovatus, a gram-negative obligate anaerobe from the human colon, can ferment the branched galactomannan guar gum. Previously, three enzymes involved in guar gum breakdown were characterized. The expression of these enzymes appeared to be regulated; i.e., specific activities were higher in extracts from bacteria grown on guar gum than in extracts from bacteria grown on the monosaccharide constituents of guar gum, mannose and galactose. In the present study, we used two-dimensional gel analysis to determine the total number of B. ovatus proteins enhanced during growth on guar gum. Twelve soluble proteins and 20 membrane proteins were expressed at higher levels in guar gum-grown cells than in galactose-grown cells. An unexpected finding was that the expression of the two galactomannanases was induced by glucose as well as guar gum. Three other proteins, one membrane protein and two soluble proteins, had this same expression pattern. The remainder of the guar gum-associated proteins seen on two dimensional gels and the guar gum-associated alpha-galactosidase were induced in cells grown on guar gum but not in cells grown on glucose. Two transposon generated mutants (M-5 and M-7) that could not grow on guar gum were isolated. Both mutants still expressed the galactomannanases and the alpha-galactosidase. They also still expressed all of the guar gum-associated proteins that could be detected in two-dimensional gels of glucose-grown or galactose-grown cells. A second transposon insertion that suppressed the guar gum-negative phenotype of M 5 was isolated and characterized. The characteristics of this suppressor mutant indicated that the original transposon insertion was probably in a regulatory locus. PMID- 1622223 TI - Cloning and partial characterization of two chromosomal loci from Bacteroides ovatus that contain genes essential for growth on guar gum. AB - Previously, we isolated three transposon insertion mutants of Bacteroides ovatus (M-4, M-5, and M-7) that were unable to grow on the branched polysaccharide guar gum. In this study, we used a tetracycline resistance gene on the transposon to clone chromosomal DNA adjacent to the transposon insertions in each of the three mutants. Restriction analysis of the flanking chromosomal DNA in M-4 and M-7 revealed that the insertions in these two mutants were in the same location. The cloned DNA adjacent to the insertions in M-5 and M-7 was used as a hybridization probe to clone the wild-type loci. Two clones of about 10 kbp in size were obtained. Restriction analysis showed that these two clones did not overlap. The clone of the M-5 locus appeared to contain all of the genes affected by the M-5 insertion, but we were unable to demonstrate complementation of the M-5 mutation because of the instability of the clone in this background. Analysis of the clone of the M-7 locus showed that it contained a guar gum-regulated promoter, but the transcript originating from this promoter was not affected by the transposon insertion. Thus, the M-7 locus apparently contains at least two separate transcriptional units, the one defined by this promoter and the one interrupted by the transposon insertion. Insertion mutations downstream of the guar gum regulated promoter demonstrated that there were essential guar gum utilization genes in this region. The M-7 mutant was eliminated by the wild type in the intestinal tracts of germfree mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1622224 TI - Comparison of contact angles and adhesion to hexadecane of urogenital, dairy, and poultry lactobacilli: effect of serial culture passages. AB - The aim of this study was to examine the hydrophobicities of 23 urogenital, dairy, poultry, and American Type Culture Collection isolates of lactobacilli and to determine the effect on hydrophobicity of serially passaging the strains in liquid medium. To this end, strains were grown after isolation and identification and then serially passaged up to 20 times. Hydrophobicity was assessed through contact angle measurements on lawns of cells by using water, formamide, methylene iodide, 1-bromonaphthalene, and hexadecane as wetting agents and through measurement of their partitioning in a hexadecane-water system. The hydrophobicities of these strains varied widely, with Lactobacillus casei strains being predominantly hydrophilic and L. acidophilus strains being mostly hydrophobic. For some isolates, serial passaging was accompanied by a clear loss of hydrophobic surface properties, whereas for other strains, cultures became heterogeneous in that some cells had already lost their hydrophobic surface properties while others were still hydrophobic. Adhesion of this collection of lactobacilli to hexadecane droplets in microbial adhesion to hexadecane (MATH) tests was driven by their aversion to water rather than by their affinity for hexadecane, as concluded from the fact that hexadecane contact angles were zero for all strains. Furthermore, adhesion of the lactobacilli to hexadecane in MATH tests occurred only when the water contact angle on the cells was above 60 degrees. PMID- 1622225 TI - Mineralization of glucose and lignocellulose by four arctic freshwater sediments in response to nutrient enrichment. AB - Microbial biomass and activity were examined in four different arctic sediments: littoral lake sediment and profundal lake sediment from Toolik Lake, Alaska, thaw pond sediment, and eroding river bank peat. The thaw pond sediment had the largest viable microbial biomass, while the profundal sediment had the smallest. Rates of glucose or acetate incorporation into lipids, glucose mineralization, and lignocellulose mineralization (all normalized per unit of biomass) were highest in the river peat sample, however. The kinetics of glucose mineralization in the profundal sediment were very different from those in the other three samples: although the initial rate of mineralization was five times lower than that in the peat and two times lower than that in the littoral and thaw pond sediments, the maximum amount of 14CO2 evolved from [14C]glucose eventually equaled that in the peat and exceeded that in the littoral and thaw pond sediments by 2.0 and 3.5 times, respectively. Carex aquatilis [14C-cellulose]- and [14C-lignin]lignocellulose mineralization rates in the profundal sediment equaled or exceeded those in the littoral sediment after 16 and 46 days, but the pattern of nutrient limitation differed: the profundal sediment was the only one sampled that exhibited nitrogen limitation, while the other three sediments appeared to be limited primarily by phosphorus. The addition of nitrogen and phosphorus together had no cumulative effects on lignocellulose mineralization. When the rates of mineralization or incorporation of glucose are compared with those of lignocellulose, the results of this study indicate that profundal sediment communities may be better able to utilize the more recalcitrant substrates relative to the labile substrates than microbial communities from sediments rich in detritus and standing macrophytes. PMID- 1622226 TI - Use of polymerase chain reaction for detection of Listeria monocytogenes in food. AB - A previously described polymerase chain reaction (PCR) assay (B. Furrer, U. Candrian, C. Hofelein, and J. Luthy, J. Appl. Bacteriol. 70:372-379, 1991) was used to analyze food for the presence of Listeria monocytogenes. Food samples were artificially contaminated to develop two procedures to detect the organism following enrichment steps. Procedure A was based on dilution of the enrichment broth followed by lysis of the bacteria and direct analysis of the lysate with PCR. With procedure A and artificially contaminated food samples, it was possible to detect fewer than 10 bacteria per 10 g of food. In procedure B, centrifugation was used to concentrate bacteria before lysis and PCR. With procedure A, 330 naturally contaminated food samples of several types were analyzed. Twenty samples were found to be positive for L. monocytogenes, which was in agreement with the classical culture technique. By using procedure B on a subset of 100 food samples, 14 were found to be positive by PCR whereas the classical culture method detected only 13. Analysis times, including enrichment steps, were 56 and 32 h with procedures A and B, respectively. PMID- 1622227 TI - Styrene formation by the decomposition by Pichia carsonii of trans-cinnamic acid added to a ground fish product. AB - It is not well known how the formation of styrene by microorganisms can occur in foods. In this study, we described and characterized the production of styrene by a yeast isolated from chikuwa fish paste. The styrene was not detected in fresh and normal food products nor in the food package's plastic film. The food containing styrene contained cinnamic acid as an antimicrobial agent and spice, and it was contaminated by 5.4 x 10(6) CFU of a yeast per gram. On the basis of morphological and biochemical features, the yeast isolated was determined to be a strain of Pichia carsonii, now designated strain CHI. Strain CHI, which was able to grow on cinnamic acid, had the ability to form styrene from trans-cinnamic acid via trans-p-coumaric and caffeic acids. The MIC of trans-cinnamic acid against strain CHI was 230 micrograms/ml. Strain CHI thrived well at pH 5.0 and 26.0 degrees C and was tolerant to 20% NaCl. Styrene was subsequently produced in ground fish meat containing cinnamic acid into which strain CHI had been inoculated. The yeast was found to be an environmental contaminant in food processing plants of the chikuwa manufacturer. PMID- 1622228 TI - Insecticidal properties of genetically engineered baculoviruses expressing an insect juvenile hormone esterase gene. AB - Exploring the possibility of enhancing the properties of baculoviruses as biological control agents of insect pests, we tested the effect of expressing an insect gene (jhe) encoding juvenile hormone esterase. Juvenile hormone esterase inactivates juvenile hormone, which regulates the outcome of an insect molt. A cDNA encoding the juvenile hormone esterase of Heliothis virescens was inserted into the genome of Autographa californica nuclear polyhedrosis virus such that the gene was expressed under the control of a strong, modified viral promoter. This virus, however, naturally encodes an ecdysteroid UDP-glucosyltransferase which inactivates ecdysone, the hormone which initiates molting. Since ecdysteroid UDP-glucosyltransferase could mask the effects of jhe expression by blocking molting entirely, jhe-expressing viruses in which the ecdysteroid UDP glucosyltransferase gene was deleted or disrupted were constructed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of proteins from infected cells revealed several intracellular proteins and two major secreted proteins which reacted with antibodies to authentic juvenile hormone esterase. Western blot analysis coupled with tunicamycin treatment indicated that differential glycosylation was responsible for the multiple products. Hemolymph of recombinant virus-infected fourth-instar Trichoplusia ni larvae contained levels of juvenile hormone esterase activity 40-fold higher than maximal levels found in uninfected larvae. However, little or no difference in developmental characteristics, weight gain, or time of mortality was observed between insects infected with the jhe-expressing viruses and control viruses. PMID- 1622229 TI - Heavy metals alter the electrokinetic properties of bacteria, yeasts, and clay minerals. AB - The electrokinetic patterns of four bacterial species (Bacillus subtilis, Bacillus megaterium, Pseudomonas aeruginosa, and Agrobacterium radiobacter), two yeasts (Saccharomyces cerevisiae and Candida albicans), and two clay minerals (montmorillonite and kaolinite) in the presence of the chloride salts of the heavy metals, Cd, Cr, Cu, Hg, Ni, Pb, and Zn, and of Na and Mg were determined by microelectrophoresis. The cells and kaolinite were net negatively charged at pH values above their isoelectric points (pI) in the presence of Na, Mg, Hg, and Pb at an ionic strength (mu) of 3 x 10(-4); montmorillonite has no pI and was net negatively charged at all pH values in the presence of these metals. However, the charge of some bacteria, S. cerevisiae, and kaolinite changed to a net positive charge (charge reversal) in the presence of Cd, Cr, Cu, Ni, and Zn at pH values above 5.0 (the pH at which charge reversal occurred differed with the metal) and then, at higher pH values, again became negative. The charge of the bacteria and S. cerevisiae also reversed in solutions of Cu and Ni with a mu of greater than 3 x 10(-4), whereas there was no reversal in solutions with a mu of less than 3 x 10(-4). The clays became net positively charged when the mu of Cu was greater than 3 x 10(-4) and that of Ni was greater than 1.5 x 10(-4). The charge of the cells and clays also reversed in solutions containing both Mg and Ni or both Cu and Ni (except montmorillonite) but not in solutions containing both Mg and Cu (except kaolinite) (mu = 3 x 10(-4)). The pIs of the cells in the presence of the heavy metals were at either higher or lower pH values than in the presence of Na and Mg. Exposure of the cells to the various metals at pH values from 2 to 9 for the short times (ca. 10 min) required to measure the electrophoretic mobility did not affect their viability. The specific adsorption on the cells and clays of the hydrolyzed species of some of the heavy metals that formed at higher pH values was probably responsible for the charge reversal. These results suggest that the toxicity of some heavy metals to microorganisms varies with pH because the hydrolyzed speciation forms of these metals, which occur at higher pH values, bind on the cell surface and alter the net charge of the cell.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1622230 TI - VIRTUS, a model of virus transport in unsaturated soils. AB - As a result of the recently proposed mandatory groundwater disinfection requirements to inactivate viruses in potable water supplies, there has been increasing interest in virus fate and transport in the subsurface. Several models have been developed to predict the fate of viruses in groundwater, but few include transport in the unsaturated zone and all require a constant virus inactivation rate. These are serious limitations in the models, as it has been well documented that considerable virus removal occurs in the unsaturated zone and that the inactivation rate of viruses is dependent on environmental conditions. The purpose of this research was to develop a predictive model of virus fate and transport in unsaturated soils that allows the virus inactivation rate to vary on the basis of changes in soil temperature. The model was developed on the basis of the law of mass conservation of a contaminant in porous media and couples the flows of water, viruses, and heat through the soil. Model predictions were compared with measured data of virus transport in laboratory column studies and, with the exception of one point, were within the 95% confidence limits of the measured concentrations. The model should be a useful tool for anyone wishing to estimate the number of viruses entering groundwater after traveling through the soil from a contamination source. In addition, model simulations were performed to identify parameters that have a large effect on the results. This information can be used to help design experiments so that important variables are measured accurately. PMID- 1622231 TI - Some growth and metabolic characteristics of monensin-sensitive and monensin resistant strains of Prevotella (Bacteroides) ruminicola. AB - New strains with enhanced resistance to monensin were developed from Prevotella (Bacteroides) ruminicola subsp. ruminicola 23 and P. ruminicola subsp. brevis GA33 by stepwise exposure to increasing concentrations of monensin. The resulting resistant strains (23MR2 and GA33MR) could initiate growth in concentrations of monensin which were 4 to 40 times greater than those which inhibited the parental strains. Resistant strains also showed enhanced resistance to nigericin and combinations of monensin and nigericin but retained sensitivity to lasalocid. Glucose utilization in cultures of the monensin-sensitive strains (23 and GA33) and one monensin-resistant strain (23MR2) was retarded but not completely inhibited when logarithmic cultures were challenged with monensin (10 mg/liter). Monensin challenge of cultures of the two monensin-sensitive strains (23 and GA33) was characterized by 78 and 51% decreases in protein yield (milligrams of protein per mole of glucose utilized), respectively. Protein yields in cultures of resistant strain 23MR2 were decreased by only 21% following monensin challenge. Cell yields and rates of glucose utilization by resistant strains GA33MR were not decreased by challenge with 10 mg of monensin per liter. Resistant strains produced greater relative proportions of propionate and less acetate than the corresponding sensitive strains. The relative amounts of succinate produced were greater in cultures of strains 23, GA33, and 23MR2 following monensin challenge. However, only minor changes in end product formation were associate with monensin challenge of resistant strain GA33MR. These results suggest that monensin has significant effects on both the growth characteristics and metabolic activities of these predominant, gram-negative ruminal bacteria. PMID- 1622232 TI - Long-term starvation survival of Yersinia ruckeri at different salinities studied by microscopical and flow cytometric methods. AB - Cultures of three strains of the fish pathogenic bacterium Yersinia ruckeri survived starvation in unsupplemented water for at least 4 months. At salinities of 0 to 20/1000 there were no detectable changes in CFU during the first 3 days of starvation and only a small decrease during the following 4 months, whereas at 35/1000 salinity, the survival potential of the cultures was markedly reduced. These results suggest that Y. ruckeri may survive for long periods in freshwater and brackish environments after an outbreak of enteric redmouth disease. Survival was also examined by use of the direct viable count method, and we show that this method can be combined with flow cytometry for automatic counting of viable bacteria. By flow cytometry, it was shown that genome replication initiated before the onset of starvation was completed, during the initial phase of starvation, and that starved cells could contain up to six genomes per cell. PMID- 1622233 TI - Enrichment and properties of an anaerobic mixed culture reductively dechlorinating 1,2,3-trichlorobenzene to 1,3-dichlorobenzene. AB - Hexachlorobenzene (HCB), pentachlorobenzene (QCB), all three isomers of tetrachlorobenzene (TeCB), 1,2,3-trichlorobenzene (1,2,3-TCB), and 1,2,4-TCB were reductively dechlorinated by enrichment cultures in the presence of lactate, glucose, ethanol, or isopropanol as the electron donor. The enrichment cultures originated from percolation columns filled with Rhine River sediment in which dechlorination of TCBs and dichlorobenzenes (DCBs) occurred. A stable consortium obtained by transfer on lactate as the energy and carbon source in the presence of 1,2,3-TCB dechlorinated this isomer stoichiometrically to 1,3-DCB. Dechlorinating activity could only be maintained when an electron donor was added. Lactate, ethanol, and hydrogen appeared to be the best substrates. Optimal temperature and pH for dechlorination were 30 degrees C and 7.2, respectively. The specificity of the enrichment on lactate and 1,2,3-TCB was tested after approximately 60 transfers (after 2.5 years). HCB and QCB were stoichiometrically dechlorinated to 1,3,5-TCB and minor amounts of 1,2,4-TCB. 1,3,5-TCB was the sole product formed from 1,2,3,5-TeCB, while 1,2,3,4-TeCB and 1,2,4,5-TeCB were converted to 1,2,4-TCB. 1,2,4-TCB, 1,3,5-TCB, and the three isomers of DCB were not dechlorinated during 4 weeks of incubation. For further enrichment of the 1,2,3-TCB-dechlorinating bacteria, a two-liquid-phase (hexadecane-water) system was used with hydrogen as the electron donor and 1,2,3-TCB or CO2 as the electron acceptor. Methanogens and acetogens were the major substrate-competing (H2-CO2) microorganisms in the two-liquid-phase system. Inhibition of methanogenesis by 2 bromoethanesulfonic acid did not influence dechlorination, and acetogens which were isolated from the enrichment culture did not have dechlorinating activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1622234 TI - Characteristics of a new cellulolytic Clostridium sp. isolated from pig intestinal tract. AB - Gram-positive, spore-forming, motile, cellulolytic rods were isolated from 10(7) dilutions of pig fecal samples. The pigs had previously been fed pure cultures of the ruminal cellulolytic organism Clostridium longisporum. Isolates formed terminal to subterminal spores, and a fermentable carbohydrate was required for growth. Besides cellulose, the isolates utilized cellobiose, glycogen, maltose, and starch. However, glucose, fructose, sucrose, pectin, and xylose were not used as energy sources. Major fermentation products included formate and butyrate. The isolates did not digest proteins from gelatin or milk. Unlike C. longisporum, which has limited ability to degrade cell wall components from grasses (switchgrass, bromegrass, and ryegrass), the swine isolates were equally effective in degrading these components from both alfalfa and grasses. The extent of degradation was equal to or better than that observed with the predominant ruminal cellulolytic organisms. On the basis of morphology, motility, spore formation, fermentation products, and the ability to hydrolyze cellulose, the isolates are considered to be a new species of the genus Clostridium. It is unclear whether C. longisporum played a role in the establishment or occurrence of this newly described cellulolytic species. This is the first report of a cellulolytic Clostridium sp. isolated from the pig intestinal tract. PMID- 1622235 TI - Cloning and expression of the cryIVD gene of Bacillus thuringiensis subsp. israelensis in the cyanobacterium Agmenellum quadruplicatum PR-6 and its resulting larvicidal activity. AB - A mosquitocidal cyanobacterium has been developed by introducing the mosquito toxic cryIVD gene from Bacillus thuringiensis subsp. israelensis into the unicellular cyanobacterium Agmenellum quadruplicatum PR-6 (Synechococcus sp. strain PCC 7002). The cryIVD gene was introduced into the cyanobacterium on a derivative of the PR-6 expression vector pAQE19 delta Sal in which the cryIVD gene was translationally fused to the initial coding sequence of the highly expressed PR-6 cpcB gene. Coomassie blue staining and immunoblot analysis of gel fractionated cell extract polypeptides indicate that the cpcB-cryIVD gene fusion is expressed at high levels in the cyanobacterial cells, with little or no apparent degradation of the cryIVD gene product. Larvicidal assays revealed that freshly hatched Culex pipiens mosquito larvae readily ingested the transformed cyanobacteria and that the cells proved to be toxic to the larvae. PMID- 1622236 TI - Isolation and characterization of acetic acid-tolerant galactose-fermenting strains of Saccharomyces cerevisiae from a spent sulfite liquor fermentation plant. AB - From a continuous spent sulfite liquor fermentation plant, two species of yeast were isolated, Saccharomyces cerevisiae and Pichia membranaefaciens. One of the isolates of S. cerevisiae, no. 3, was heavily flocculating and produced a higher ethanol yield from spent sulfite liquor than did commercial baker's yeast. The greatest difference between isolate 3 and baker's yeast was that of galactose fermentation, even when galactose utilization was induced, i.e., when they were grown in the presence of galactose, prior to fermentation. Without acetic acid present, both baker's yeast and isolate 3 fermented glucose and galactose sequentially. Galactose fermentation with baker's yeast was strongly inhibited by acetic acid at pH values below 6. Isolate 3 fermented galactose, glucose, and mannose without catabolite repression in the presence of acetic acid, even at pH 4.5. The xylose reductase (EC 1.1.1.21) and xylitol dehydrogenase (EC 1.1.1.9) activities were determined in some of the isolates as well as in two strains of S. cerevisiae (ATCC 24860 and baker's yeast) and Pichia stipitis CBS 6054. The S. cerevisiae strains manifested xylose reductase activity that was 2 orders of magnitude less than the corresponding P. stipitis value of 890 nmol/min/mg of protein. The xylose dehydrogenase activity was 1 order of magnitude less than the corresponding activity of P. stipitis (330 nmol/min/mg of protein). PMID- 1622237 TI - Conjugal transfer in Lactococcus lactis of a 68-kilobase-pair chromosomal fragment containing the structural gene for the peptide bacteriocin nisin. AB - Nisin-producing transconjugants were generated by mating nisin-producing strains of Lactococcus lactis subsp. lactis with derivatives of L. lactis subsp. lactis LM0230. The sucrose-utilizing ability and reduced bacteriophage sensitivity were also transferred with the nisin-producing character. Pulsed-field gel electrophoretic analysis of genomic DNA from donor, recipient, and nisin producing transconjugants indicated that 68 kbp of DNA was transferred from the chromosome of the donor into the chromosome of the recipient in the conjugation process. The location of the transferred nisin structural gene spaN in the transconjugant HID500 was not stable, and cultures of strain HID500 were a mixture of different genotypes in which spaN was located at different positions in the chromosome on different SmaI fragments. ApaI, BglI, BssHII, NciI, SalI, and SmaI digests of genomic DNA were used to map the location of spaN in a donor (DL11) and a nisin-producing transconjugant (HID504). PMID- 1622238 TI - Overproduction of threonine by Saccharomyces cerevisiae mutants resistant to hydroxynorvaline. AB - In this work, we isolated and characterized mutants that overproduce threonine from Saccharomyces cerevisiae. The mutants were selected for resistance to the threonine analog alpha-amino-beta-hydroxynorvalerate (hydroxynorvaline), and, of these, the ones able to excrete threonine to the medium were chosen. The mutant strains produce between 15 and 30 times more threonine than the wild type does, and, to a lesser degree, they also accumulate isoleucine. Genetic and biochemical studies have revealed that the threonine overproduction is, in all cases studied, associated with the presence in the strain of a HOM3 allele coding for a mutant aspartate kinase that is totally or partially insensitive to feedback inhibition by threonine. This enzyme seems, therefore, to be crucial in the regulation of threonine biosynthesis in S. cerevisiae. The results obtained suggest that this strategy could be efficiently applied to the isolation of threonine-overproducing strains of yeasts other than S. cerevisiae, even those used industrially. PMID- 1622239 TI - Bioremediation of soils contaminated with the herbicide 2-sec-butyl-4,6 dinitrophenol (dinoseb). AB - A novel soil treatment method for achieving the removal of dinoseb (2-sec-butyl 4,6-dinitrophenol) from contaminated soils was investigated. One soil contained dinoseb as the major contaminant, although several other hazardous compounds were also present. A second soil was highly contaminated with dinoseb. Dinoseb was not degraded in these soils under the aerobic conditions at each site. Pretreatment of the soils by the addition of a starchy potato-processing by-product and flooding with phosphate buffer stimulated the consumption of oxygen and nitrate from the soils, thereby lowering the redox potential and creating anaerobic conditions. Anaerobiosis (Eh less than -200 mV) promoted the establishment of an anaerobic microbial consortium that degraded dinoseb completely, without the formation of the polymerization products seen under aerobic or microaerophilic conditions. When dinoseb was present at low concentrations in a chronically contaminated soil, the natural microflora was capable of establishing anaerobic conditions and degrading dinoseb as a result of starch degradation. Inoculation of this soil with an aerobic starch-degrading microorganism and then an acclimated, anaerobic, dinoseb-degrading consortium did not improve dinoseb degradation. In a second acutely contaminated soil, these inoculations improved dinoseb degradation rates over those of uninoculated controls. PMID- 1622240 TI - Effect of bacterial extracellular polymers on the saturated hydraulic conductivity of sand columns. AB - Columns were packed with clean quartz sand, sterilized, and inoculated with different strains of bacteria, which multiplied within the sand at the expense of a continuous supply of fresh nutrient medium. The saturated hydraulic conductivity (HCsat) of the sand was monitored over time. Among the four bacterial strains tested, one formed a capsule, one produced slime layers, and two did not produce any detectable exopolymers. The last two strains were nonmucoid variants of the first two. Only one strain, the slime producer, had a large impact on the HCsat. The production of exopolymers had no effect on either cell multiplication within or movement through the sand columns. Therefore, the HCsat reduction observed with the slime producer was tentatively attributed to the obstruction of flow channels with slime. Compared with the results with Arthrobacter sp. strain AK19 used in a previous study, there was a 100-fold increase in detachment from the solid substratum and movement through the sand of the strains used in this study. All strains induced severe clogging when they colonized the inlet chamber of the columns. Under these conditions, the inlet end was covered by a confluent mat with an extremely low HCsat. PMID- 1622241 TI - Acyloin formation by benzoylformate decarboxylase from Pseudomonas putida. AB - Whole cells and cell extracts of Pseudomonas putida grown in a medium containing ammonium mandelate have the capacity to produce the acyloin compound 2 hydroxypropiophenone when incubated with benzoylformate and acetaldehyde. Benzaldehyde and benzyl alcohol were formed as reaction by-products. The enantiomeric excess of the 2-hydroxypropiophenone product was found to be 91 to 92%. The absolute configuration of the enzymatically prepared product at the carbinol carbon was found to be S. The thiamine PPi-linked enzyme benzoylformate decarboxylase, purified to give a single protein band on polyacrylamide gel electrophoresis, was shown to be responsible for the catalysis of this novel condensation reaction. PMID- 1622242 TI - Isoliquiritigenin, a strong nod gene- and glyceollin resistance-inducing flavonoid from soybean root exudate. AB - Isoflavonoid signal molecules from soybean (Glycine max (L.) Merr.) seed and root exudate induce the transcription of nodulation (nod) genes in Bradyrhizobium japonicum. In this study, a new compound with symbiotic activity was isolated from soybean root exudate. The isolated 2',4',4-trihydroxychalcone (isoliquiritigenin) is characterized by its strong inducing activity for the nod genes of B. japonicum. These genes are already induced at concentrations 1 order of magnitude below those required of the previously described isoflavonoid inducers genistein and daidzein. Isoliquiritigenin is also a potent inducer of glyceollin resistance in B. japonicum, which renders this bacterium insensitive to potentially bactericidal concentrations of glyceollin, the phytoalexin of G. max. No chemotactic effect of isoliquiritigenin was observed. The highly efficient induction of nod genes and glyceollin resistance by isoliquiritigenin suggests the ecological significance of this compound, although it is not a major flavonoid constituent of the soybean root exudate in quantitative terms. PMID- 1622243 TI - Excretion of ammonium by a nifL mutant of Azotobacter vinelandii fixing nitrogen. AB - A mutation in the gene upstream of nifA in Azotobacter vinelandii was introduced into the chromosome to replace the corresponding wild-type region. The resulting mutant, MV376, produced nitrogenase constitutively in the presence of 15 mM ammonium. When introduced into a nifH-lacZ fusion strain, the mutation permitted beta-galactosidase production in the presence of ammonium. The gene upstream of nifA is therefore designated nifL because of its similarity to the Klebsiella pneumoniae nifL gene in proximity to nifA, in mutant phenotype, and in amino acid sequence of the gene product. The A. vinelandii nifL mutant MV376 excreted significant quantities of ammonium (approximately 10 mM) during diazotrophic growth. In contrast, ammonium excretion during diazotrophy was much lower in a K. pneumoniae nifL deletion mutant (maximum, 0.15 mM) but significantly higher than in NifL+ K. pneumoniae. The expression of the A. vinelandii nifA gene, unlike that of K. pneumoniae, was not repressed by ammonium. PMID- 1622244 TI - Chlorobenzene degradation by bacteria isolated from contaminated groundwater. AB - Bacterial isolates were obtained from groundwater and soils contaminated with chlorobenzene (CB). The isolates were tested to determine whether the natural community could remove the groundwater contaminants. These isolates were identified and characterized as to their ability to grow on CB and related aromatic compounds. The complete consortium could mineralize approximately 54% of the CB within 7 days, with no accumulation of 3-chlorocatechol. Metabolic pathways were evaluated for several isolates. One phenotype was characterized by the ability to degrade CB by the modified ortho pathway. One strain also degraded p-dichlorobenzene by using the same pathway. Isolates exhibiting a second phenotype degraded p-cresol, benzene, and phenol by the classical ortho pathway and accumulated 3-chlorocatechol when grown in the presence of CB. Strains of the third phenotype grew on complex media in the presence of CB but did not transform any of the aromatic compounds tested. The results suggest that the indigenous microbial community at the contaminated site would be able to degrade CB if provided with the appropriate conditions. PMID- 1622245 TI - Immunocytochemical localization of laccase L1 in wood decayed by Rigidoporus lignosus. AB - The cellular distribution of laccase L1 during degradation of wood chips by Rigidoporus lignosus, a tropical white rot fungus, was investigated by using anti laccase L1 polyclonal antisera in conjunction with immunolabeling techniques. The enzyme was localized in the fungal cytoplasm and was associated with the plasmalemma and the fungal cell wall. An extracellular sheath, often observed around fungal cells, often contained laccase molecules. Diffusion of laccase within apparently unaltered wood was seldom observed. The enzyme penetrated all degraded cell walls, from the secondary wall toward the primary wall, including the middle lamella. Xylem cells showing advanced stages of decay were sometimes devoid of significant labeling. These data suggest that the initial attack on wood was not performed by laccase L1 of R. lignosus. Previous alteration of the lignocellulose complex may facilitate the movement of laccase within the wood cell walls. This immunogold study revealed that laccase localization during wood degradation seems limited not in space but in time. PMID- 1622246 TI - Determination of the respiration kinetics for mycelial pellets of Phanerochaete chrysosporium. AB - In mycelial pellet cultures of the white rot basidiomycete Phanerochaete chrysosporium, low oxygen concentration negatively affects the production of the extracellular lignin peroxidases and manganese peroxidases which are key components of the lignin-degrading system of this organism. To test the hypothesis that oxygen limitation in the pellets is responsible for this effect, oxygen microelectrodes were used to determine oxygen concentration gradients within the mycelial pellets of P. chrysosporium. Pellets were removed from oxygenated cultures, allowed to equilibrate with air, and probed with oxygen microelectrodes. The oxygen profiles were modelled assuming that O2 uptake follows a Michaelis-Menten relationship. The Vmax and Km values for oxygen uptake were 0.76 +/- 0.10 g/m3 of pellet per s and 0.5 +/- 0.3 g/m3, respectively. These kinetic values were used to predict respiration rates in air-flushed cultures, oxygen-flushed cultures, and cultures with large pellets (diameter greater than 6 mm). The predicted respiration rates were independently validated by experimentally measuring the evolution of carbon dioxide from whole cultures. PMID- 1622247 TI - Inhibition of existing denitrification enzyme activity by chloramphenicol. AB - Chloramphenicol completely inhibited the activity of existing denitrification enzymes in acetylene-block incubations with (i) sediments from a nitrate contaminated aquifer and (ii) a continuous culture of denitrifying groundwater bacteria. Control flasks with no antibiotic produced significant amounts of nitrous oxide in the same time period. Amendment with chloramphenicol after nitrous oxide production had begun resulted in a significant decrease in the rate of nitrous oxide production. Chloramphenicol also decreased (greater than 50%) the activity of existing denitrification enzymes in pure cultures of Pseudomonas denitrificans that were harvested during log-phase growth and maintained for 2 weeks in a starvation medium lacking electron donor. Short-term time courses of nitrate consumption and nitrous oxide production in the presence of acetylene with P. denitrificans undergoing carbon starvation were performed under optimal conditions designed to mimic denitrification enzyme activity assays used with soils. Time courses were linear for both chloramphenicol and control flasks, and rate estimates for the two treatments were significantly different at the 95% confidence level. Complete or partial inhibition of existing enzyme activity is not consistent with the current understanding of the mode of action of chloramphenicol or current practice, in which the compound is frequently employed to inhibit de novo protein synthesis during the course of microbial activity assays. The results of this study demonstrate that chloramphenicol amendment can inhibit the activity of existing denitrification enzymes and suggest that caution is needed in the design and interpretation of denitrification activity assays in which chloramphenicol is used to prevent new protein synthesis. PMID- 1622248 TI - Tannin-protein complex-degrading enterobacteria isolated from the alimentary tracts of koalas and a selective medium for their enumeration. AB - Tannin-protein complex (T-PC)-degrading enterobacteria (T-PCDE) were isolated from the feces and from a layer of bacteria attached to the cecal wall of koalas. The T-PCDE were facultatively anaerobic, gram-negative, pleomorphic, nonmotile bacilli. The bacteria were also oxidase and catalase negative and resistant to vancomycin, reduced nitrates to nitrites, and grew on MacConkey agar. Growth on tannin-treated agar media showed a distinctive clear zone around the colony. From these observations, a selective agar plate medium (vancomycin- and tannin-treated Wilkins-Chalgren anaerobe agar) was developed to enumerate T-PCDE isolated from the feces of koalas. This medium was highly selective in the enumeration of the fecal T-PCDE and inhibited the growth of concomitant T-PC-degrading Streptococcus bovis. The T-PCDE were isolated from 10 of the 12 captive koalas studied; in 8 of these 10 koalas, the facultatively anaerobic bacterial flora was dominated (more than 60%) by T-PCDE. Viable numbers of T-PCDE were, in most of the animals, much larger (more than 100 times) than the numbers of T-PC-degrading S. bovis, suggesting that T-PCDE played a more active role in digesting T-PC in the alimentary tracts of koalas. PMID- 1622249 TI - Dipstick immunoassay to detect enterohemorrhagic Escherichia coli O157:H7 in retail ground beef. AB - A sensitive and easy-to-perform dipstick immunoassay to detect Escherichia coli O157:H7 in retail ground beef was developed by using a sandwich-type assay (with a polyclonal antibody to E. coli O157 as the capture antibody and a monoclonal antibody to E. coli O157:H7 as the detection antibody) on a hydrophobic polyvinylidine difluoride-based membrane. E. coli O157:H7 in ground beef could be detected within 16 h, including incubation for 12 h in enrichment broth and the immunoassay, which takes 4 h. Pure culture cell suspensions of 10(5) or 10(6) E. coli O157:H7 organisms per ml produced intense color reactions in the immunoassay, whereas faint but detectable reactions occurred with 10(3) CFU/ml. The sensitivity of the combined enrichment-immunoassay procedure as determined by using ground beef inoculated with E. coli O157:H7 was 0.1 to 1.3 cells per g, with a false-positive rate of 2.0%. A survey of retail ground beef using this procedure revealed that 1 of 76 samples was contaminated by E. coli O157:H7. PMID- 1622250 TI - Rapid genomic fingerprinting of Lactococcus lactis strains by arbitrarily primed polymerase chain reaction with 32P and fluorescent labels. AB - Arbitrarily primed polymerase chain reaction, with incorporation of either radioactive or fluorescent labels, was used as a rapid and sensitive method for obtaining genomic fingerprints of strains of Lactococcus lactis. Closely related strains produced almost identical fingerprints. Fingerprints of other strains showed only some similarities. PMID- 1622251 TI - Degradation of triglycerides by a pseudomonad isolated from milk: molecular analysis of a lipase-encoding gene and its expression in Escherichia coli. AB - Psychrotrophic lipolytic bacteria represent a significant problem in the storage of refrigerated dairy products. A lipase-encoding gene has been cloned and characterized from a highly lipolytic strain of Pseudomonas. The nucleotide sequence of the gene predicts a polypeptide of M(r) 49,905, which was identified when the gene was expressed in Escherichia coli. PMID- 1622252 TI - Evidence for a correlation between auxin production and host plant species among strains of Pseudomonas syringae subsp. savastanoi. AB - Auxin production by 131 strains of Pseudomonas syringae subsp. savastanoi was investigated with the aim of looking for correlations among this characteristic and the origin of the strains, the types of symptoms, and the host plant. Most of the P.syringae subsp. savastanoi strains, except those isolated from ash, produced auxin and harbored iaa genes. Among ash strains, which were pathogenic only on ash, only 2 out of 33 were found to produce auxin and to harbor iaa genes. PMID- 1622253 TI - Demonstration of cel operon expression of Escherichia coli, Salmonella typhimurium, and Pseudomonas aeruginosa at elevated temperatures refractory to their growth. AB - When Escherichia coli was incubated at the growth-refractory temperatures of 48 and 54 degrees C, expression of the cel operon was demonstrated by phospho-beta glucosidase activity. This enzyme activity was also detected at the growth refractory temperatures in Salmonella typhimurium and Pseudomonas aeruginosa. Thermotolerant and mesothermophilic mutants of E. coli, S. typhimurium, and P. aeruginosa, able to grow with generation times of 30 to 40 min at 48 and 54 degrees C, exhibited phospho-beta-glucosidase activity at their growth temperatures of 48 and 54 degrees C. Thus, the cel operon previously described as a cryptic operon in E. coli and S. typhimurium was found to be expressed at growth-refractory temperatures of the mesophilic parent and growth-permissive temperatures (48 and 54 degrees C) of the thermotolerant and mesothermophilic mutants. PMID- 1622254 TI - Antimicrobial action of nisin against Salmonella typhimurium lipopolysaccharide mutants. AB - The antimicrobial activity of nisin against outer membrane lipopolysaccharide mutants of Salmonella typhimurium LT2 was investigated. Nisin sensitivity was associated with the extent of saccharide deletions from the outer membrane core oligosaccharide. The results indicated that the core oligosaccharide in lipopolysaccharide plays a role in nisin sensitivity. PMID- 1622255 TI - High-pressure, high-temperature bioreactor for comparing effects of hyperbaric and hydrostatic pressure on bacterial growth. AB - We describe a high-pressure reactor system suitable for simultaneous hyperbaric and hydrostatic pressurization of bacterial cultures at elevated temperatures. For the deep-sea thermophile ES4, the growth rate at 500 atm (1 atm = 101.29 kPa) and 95 degrees C under hydrostatic pressure was ca. three times the growth rate under hyperbaric pressure and ca. 40% higher than the growth rate at 35 atm. PMID- 1622256 TI - Use of a fluorescent redox probe for direct visualization of actively respiring bacteria. AB - The redox dye 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) was employed for direct epifluorescent microscopic enumeration of respiring bacteria in environmental samples. Oxidized CTC is nearly colorless and is nonfluorescent; however, the compound is readily reduced via electron transport activity to fluorescent, insoluble CTC-formazan, which accumulates intracellularly. Bacteria containing CTC-formazan were visualized by epifluorescence microscopy in wet mount preparations, on polycarbonate membrane filter surfaces, or in biofilms associated with optically opaque surfaces. Counterstaining of CTC-treated samples with the DNA-specific fluorochrome 4',6-diamidino-2-phenylindole allowed enumeration of active and total bacterial subpopulations within the same preparation. Municipal wastewater, groundwater, and seawater samples supplied with exogenous nutrients yielded CTC counts that were generally lower than total 4',6-diamidino-2-phenylindole counts but typically equal to or greater than standard heterotrophic (aerobic) plate counts. In unsupplemented water samples, CTC counts were typically lower than those obtained with the heterotrophic plate count method. Reduction of CTC by planktonic or biofilm-associated bacteria was suppressed by formaldehyde, presumably because of inhibition of electron transport activity and other metabolic processes. Because of their bright red fluorescence (emission maximum, 602 nm), actively respiring bacteria were readily distinguishable from abiotic particles and other background substances, which typically fluoresced at shorter wavelengths. The use of CTC greatly facilitated microscopic detection and enumeration of metabolically active (i.e., respiring) bacteria in environmental samples. PMID- 1622257 TI - Cell-associated pectinolytic and cellulolytic enzymes in Rhizobium leguminosarum biovar trifolii. AB - The involvement of Rhizobium enzymes that degrade plant cell wall polymers has long been an unresolved question about the infection process in root nodule symbiosis. Here we report the production of enzymes from Rhizobium leguminosarum bv. trifolii that degrade carboxymethyl cellulose and polypectate model substrates with sensitive methods that reliably detect the enzyme activities: a double-layer plate assay, quantitation of reducing sugars with a bicinchoninate reagent, and activity gel electrophoresis-isoelectric focusing. Both enzyme activities were (i) produced commonly by diverse wild-type strains, (ii) cell bound with at least some of the activity associated with the cell envelope, and (iii) not changed appreciably by growth in the presence of the model substrates or a flavone that activates expression of nodulation (nod) genes on the resident symbiotic plasmid (pSym). Equivalent levels of carboxymethyl cellulase activity were found in wild-type strain ANU843 and its pSym-cured derivative, ANU845, consistent with previous results of Morales et al. (V. Morales, E. Martinez Molina, and D. Hubbell, Plant Soil 80:407-415, 1984). However, polygalacturonase activity was lower in ANU845 and was not restored to wild-type levels in the recombinant derivative of pSym- ANU845 containing the common and host-specific nod genes within a 14-kb HindIII DNA fragment of pSym from ANU843 cloned on plasmid pRt032. Activity gel electrophoresis resolved three carboxymethyl cellulase isozymes of approximately 102, 56, and 33 kDa in cell extracts from ANU843. Isoelectric focusing activity gels revealed one ANU843 polygalacturonase isozyme with a pI of approximately 7.2. These studies show that R. leguminosarum bv. trifolii produces multiple enzymes that cleave glycosidic bonds in plant cell walls and that are cell bound. PMID- 1622258 TI - Biodegradation of bisphenol A and other bisphenols by a gram-negative aerobic bacterium. AB - A novel bacterium designated strain MV1 was isolated from a sludge enrichment taken from the wastewater treatment plant at a plastics manufacturing facility and shown to degrade 2,2-bis(4-hydroxyphenyl)propane (4,4'-isopropylidenediphenol or bisphenol A). Strain MV1 is a gram-negative, aerobic bacillus that grows on bisphenol A as a sole source of carbon and energy. Total carbon analysis for bisphenol A degradation demonstrated that 60% of the carbon was mineralized to CO2, 20% was associated with the bacterial cells, and 20% was converted to soluble organic compounds. Metabolic intermediates detected in the culture medium during growth on bisphenol A were identified as 4-hydroxybenzoic acid, 4 hydroxyacetophenone, 2,2-bis(4-hydroxyphenyl)-1-propanol, and 2,3-bis(4 hydroxyphenyl)-1,2-propanediol. Most of the bisphenol A degraded by strain MV1 is cleaved in some way to form 4-hydroxybenzoic acid and 4-hydroxyacetophenone, which are subsequently mineralized or assimilated into cell carbon. In addition, about 20% of the bisphenol A is hydroxylated to form 2,2-bis(4-hydroxyphenyl)-1 propanol, which is slowly biotransformed to 2,3-bis(4-hydroxyphenyl)-1,2 propanediol. Cells that were grown on bisphenol A degraded a variety of bisphenol alkanes, hydroxylated benzoic acids, and hydroxylated acetophenones during resting-cell assays. Transmission electron microscopy of cells grown on bisphenol A revealed lipid storage granules and intracytoplasmic membranes. PMID- 1622259 TI - Oxidative degradation of phenanthrene by the ligninolytic fungus Phanerochaete chrysosporium. AB - The ligninolytic fungus Phanerochaete chrysosporium oxidized phenanthrene and phenanthrene-9,10-quinone (PQ) at their C-9 and C-10 positions to give a ring fission product, 2,2'-diphenic acid (DPA), which was identified in chromatographic and isotope dilution experiments. DPA formation from phenanthrene was somewhat greater in low-nitrogen (ligninolytic) cultures than in high nitrogen (nonligninolytic) cultures and did not occur in uninoculated cultures. The oxidation of PQ to DPA involved both fungal and abiotic mechanisms, was unaffected by the level of nitrogen added, and was significantly faster than the cleavage of phenanthrene to DPA. Phenanthrene-trans-9,10-dihydrodiol, which was previously shown to be the principal phenanthrene metabolite in nonligninolytic P. chrysosporium cultures, was not formed in the ligninolytic cultures employed here. These results suggest that phenanthrene degradation by ligninolytic P. chrysosporium proceeds in order from phenanthrene----PQ----DPA, involves both ligninolytic and nonligninolytic enzymes, and is not initiated by a classical microsomal cytochrome P-450. The extracellular lignin peroxidases of P. chrysosporium were not able to oxidize phenanthrene in vitro and therefore are also unlikely to catalyze the first step of phenanthrene degradation in vivo. Both phenanthrene and PQ were mineralized to similar extents by the fungus, which supports the intermediacy of PQ in phenanthrene degradation, but both compounds were mineralized significantly less than the structurally related lignin peroxidase substrate pyrene was. PMID- 1622260 TI - Conversion of cis unsaturated fatty acids to trans, a possible mechanism for the protection of phenol-degrading Pseudomonas putida P8 from substrate toxicity. AB - A trans unsaturated fatty acid was found as a major constituent in the lipids of Pseudomonas putida P8. The fatty acid was identified as 9-trans-hexadecenoic acid by gas chromatography, argentation thin-layer chromatography, and infrared absorption spectrometry. Growing cells of P. putida P8 reacted to the presence of sublethal concentrations of phenol in the medium with changes in the fatty acid composition of the lipids, thereby increasing the degree of saturation. At phenol concentrations which completely inhibited the growth of P. putida, the cells were still able to increase the content of the trans unsaturated fatty acid and simultaneously to decrease the proportion of the corresponding 9-cis-hexadecenoic acid. This conversion of fatty acids was also induced by 4-chlorophenol in nongrowing cells in which the de novo synthesis of lipids had stopped, as shown by incorporation experiments with labeled acetate. The isomerization of the double bond in the presence of chloramphenicol indicates a constitutively operating enzyme system. The cis-to-trans modification of the fatty acids studied here apparently is a new way of adapting the membrane fluidity to the presence of phenols, thereby compensating for the elevation of membrane permeability induced by these toxic substances. PMID- 1622261 TI - API Listeria, a new and promising one-day system to identify Listeria isolates. AB - API Listeria is a new 10-test strip for 24-h biochemical identification of Listeria isolates. With this commercial system, 85% of 646 Listeria strains, including atypical isolates selected for this study, were recognized at the species and subspecies level without a complementary test. A new test differentiates Listeria monocytogenes from L. innocua on the basis of the absence of arylamidase from the former. With this system, 97.7% (252 of 258) of the L. monocytogenes strains tested were correctly identified and differentiated from 99.4% (175 of 176) of the L. innocua strains also tested. Gram-positive bacteria other than Listeria spp. gave quite different biochemical patterns. This system considerably reduced the time needed for conventional identification, since results were available within 18 to 24 h. PMID- 1622262 TI - Heat susceptibility of aquatic mycobacteria. AB - An investigation was carried out to measure the heat susceptibility of opportunistic mycobacteria frequently isolated from domestic water supply systems. The study was conducted under standardized conditions designed to resemble those found in oligotrophic aquatic habitats. Strains of the following species were tested: Mycobacterium avium, M. chelonae, M. fortuitum, M. intracellulare, M. kansasii (two strains), M. marinum, M. phlei, M. scrofulaceum, and M. xenopi. Suspensions of the test strains were exposed to temperatures of 50, 55, 60, and 70 degrees C; samples were taken at defined intervals to determine the concentration of survivors. From these data, the decimal reduction times were calculated for each test strain and test temperature. The results indicate that M. kansasii is more susceptible to heat than Legionella pneumophila, whereas the heat susceptibilities of M. fortuitum, M. intracellulare, and M. marinum lie in the same order of magnitude as that of L. pneumophila. The strains of M. avium, M. chelonae, M. phlei, M. scrofulaceum, and M. xenopi were found to be more thermoresistant than L. pneumophila, with the highest resistance being found in M. xenopi. Thermal measures to control L. pneumophila may therefore not be sufficient to control the last five mycobacterial species in contaminated water systems. PMID- 1622263 TI - Naphthalene degradation via salicylate and gentisate by Rhodococcus sp. strain B4. AB - Rhodococcus sp. strain B4, isolated from a soil sample contaminated with polycyclic aromatic hydrocarbons, grows with naphthalene as the sole source of carbon and energy. Salicylate and gentisate were identified as intermediates in the catabolism of naphthalene. In contrast to the well-studied catabolic pathway encoded by the NAH7 plasmid of Pseudomonas putida, salicylate does not induce the genes of the naphthalene-degradative pathway in Rhodococcus sp. strain B4. The key enzymes of naphthalene degradation in Rhodococcus sp. strain B4 have unusual cofactor requirements. The 1,2-dihydroxynaphthalene oxygenase activity depends on NADH and the salicylate 5-hydroxylase requires NADPH, ATP, and coenzyme A. PMID- 1622264 TI - Hyperreiterated DNA regions are conserved among Bradyrhizobium japonicum serocluster 123 strains. AB - We have identified and cloned two DNA regions which are highly reiterated in Bradyrhizobium japonicum serocluster 123 strains. While one of the reiterated DNA regions, pFR2503, is closely linked to the B. japonicum common and genotype specific nodulation genes in strain USDA 424, the other, pMAP9, is located next to a Tn5 insertion site in a host-range extension mutant of B. japonicum USDA 438. The DNA cloned in pFR2503 and pMAP9 are reiterated 18 to 21 times, respectively, in the genomes of B. japonicum serocluster 123 strains. Gene probes from the reiterated regions share sequence homology, failed to hybridize (or hybridized poorly) to genomic DNA from other B. japonicum and Bradyrhizobium spp. strains, and did not hybridize to DNA from Rhizobium meliloti, Rhizobium fredii, Rhizobium leguminosarum biovars trifolii, phaseoli, and viceae, or Agrobacterium tumefacians. The restriction fragment length polymorphism hybridization profiles obtained by using these gene probes are useful for discriminating among serologically related B. japonicum serocluster 123 strains. PMID- 1622265 TI - Study on the epidemiology and control of Campylobacter jejuni in poultry broiler flocks. AB - Broiler flocks are frequently infected with Campylobacter jejuni. The origin of the infection is still unclear. The question of whether colonization of flocks results from transmission of C. jejuni from breeder flocks to progeny (vertical transmission) or from environmental sources (horizontal transmission) remains to be answered. Therefore, in this study samples were taken from successive broiler flocks in two broiler houses (house A on farm A and house B1 on farm B) as well as from the environment of the houses. All C. jejuni isolates were typed by using the Penner serotyping system, and part of the isolates from farm B were typed by using a randomly amplified polymorphic DNA-typing system. In poultry house A, C. jejuni was isolated from the first flock but not from subsequent flocks. In poultry house B1, C. jejuni strains of the same Penner serotypes and exhibiting identical DNA profiles were isolated from successive flocks. Infection of the flocks from a common source via horizontal pathways is suspected, while a vertical route of infection is not likely to exist. Application of measures to control horizontal transmission of C. jejuni on farm B was successful. PMID- 1622266 TI - Extracellular protease from the antarctic yeast Candida humicola. AB - The psychrotrophic, dimorphic yeast Candida humicola, isolated from Antarctic soil, secretes an acidic protease into the medium. The secretion of this protease by C. humicola was found to be dependent on the composition of the medium. In YPD or yeast nitrogen base medium containing either amino acids or ammonium sulfate as the nitrogen source, the activity of the protease in the medium was low (basal level). However, when yeast nitrogen base medium was depleted of amino acids or ammonium sulfate and supplemented with proteins, the activity of the enzyme increased. The secretion of the enzyme was greater during exponential growth at low temperatures than during growth at higher temperatures. The purified protease had a molecular mass of 36,000 Da and was inhibited by pepstatin, iodoacetamide, and sodium dodecyl sulfate. Despite the prevalent cold temperatures in Antarctica, this extracellular protease of the psychrotrophic yeast C. humicola was active at temperatures ranging from 0 to 45 degrees C, with an optimum activity at 37 degrees C. PMID- 1622267 TI - Monoclonal antibody specific for Listeria monocytogenes associated with a 66 kilodalton cell surface antigen. AB - A monoclonal antibody (MAb), EM-7G1, specific for Listeria monocytogenes was developed by using a previously developed MAb, C11E9 (A. K. Bhunia, P. H. Ball, A. T. Fuad, B. W. Kurz, J. W. Emerson, and M. G. Johnson, Infect. Immun. 59:3176 3184, 1991), to mask epitopes shared by L. monocytogenes and Listeria innocua in a 66-kDa cell surface protein. MAb EM-7G1 was an immunoglobulin subclass G1 antibody with kappa light chains. This MAb reacted with all 34 strains of L. monocytogenes tested and showed no cross-reaction with other Listeria spp. or other gram-positive or gram-negative organisms tested by enzyme-linked immunosorbent assay, dot blotting, and colony blotting. A second MAb, EM-6E11, reacted with all Listeria spp. tested but no other bacteria. In a Western blot (immunoblot) assay, EM-7G1 reacted with a crude cell surface protein of 66 kDa with a pI value of 6.7, while EM-6E11 reacted with two protein bands of 43 and 94 to 97 kDa with pI values of 4.0 and 4.3, respectively. Results with trypsin or pronase treatments indicated that the cell antigen reacting with EM-7G1 was on the surface of L. monocytogenes V7 and Scott A cells. PMID- 1622268 TI - Transformation of Bacillus subtilis by DNA bound on montmorillonite and effect of DNase on the transforming ability of bound DNA. AB - The equilibrium adsorption and binding of DNA from Bacillus subtilis on the clay mineral montmorillonite, the ability of bound DNA to transform competent cells, and the resistance of bound DNA to degradation by DNase I are reported. Maximum adsorption of DNA on the clay occurred after 90 min of contact and was followed by a plateau. Adsorption was pH dependent and was greatest at pH 1.0 (19.9 micrograms of DNA mg of clay-1) and least at pH 9.0 (10.7 micrograms of DNA mg of clay-1). The transformation frequency increased as the pH at which the clay-DNA complexes were prepared increased, and there was no transformation by clay-DNA complexes prepared at pH 1. After extensive washing with deionized distilled water (pH 5.5) or DNA buffer (pH 7.5), 21 and 28%, respectively, of the DNA remained bound. Bound DNA was capable of transforming competent cells (as was the desorbed DNA), indicating that adsorption, desorption, and binding did not alter the transforming ability of the DNA. Maximum transformation by bound DNA occurred at 37 degrees C (the other temperatures evaluated were 0, 25, and 45 degrees C). DNA bound on montmorillonite was protected against degradation by DNase, supporting the concept that "cryptic genes" may persist in the environment when bound on particulates. The concentration of DNase required to inhibit transformation by bound DNA was higher than that required to inhibit transformation by comparable amounts of free DNA, and considerably more bound than free DNase was required to inhibit transformation by the same amount of free DNA. Similarly, when DNA and DNase were bound on the same or separate samples of montmorillonite, the bound DNA was protected from the activity of DNase. PMID- 1622269 TI - Application of ribotyping for differentiating aeromonads isolated from clinical and environmental sources. AB - We have investigated the usefulness of ribotyping for the differentiation of aeromonads isolated from five patients with gastroenteritis and from the source water, treatment plant, and distribution system of a small public water supply. Aeromonas hydrophila and Aeromonas caviae were isolated from fecal specimens preserved in Cary-Blair transport medium by using blood ampicillin agar or alkaline peptone water (pH 8.4) subcultured to blood ampicillin agar plates. A. hydrophila, Aeromonas sobria, and A. caviae were isolated from duplicate 100-ml water samples by the membrane filter technique by using ampicillin dextrin agar for quantitative determination of growth and alkaline peptone water enrichment for detection of the presence or absence of aeromonads below the detection limit of the membrane filter method. In addition, free chlorine residuals and pH values were determined for all water samples and heterotrophic plate counts and total and fecal coliform analyses were performed on them. Ribotyping patterns of aeromonads recovered from well 1, detention basin, sand filter, softener, and distribution samples were compared with those of the five clinical isolates. All patient strains were unique; however, identical ribotypes of A. hydrophila and A. sobria isolated from multiple sites in the water system indicated colonization of a well, sand filters, and the softener, with the potential for sporadic contamination of distribution water. Plant operational deficiencies were noted and corrected. Ribotyping can effectively differentiate otherwise indistinguishable strains of bacteria, thus providing a powerful tool for investigation of waterborne diseases and bacteriological problems within water treatment plants and distribution systems. PMID- 1622270 TI - Reduction of nitroaromatic compounds mediated by Streptomyces sp. exudates. AB - Exudates from Streptomyces griseoflavus Tu 2484 effectively mediated electron transfer between hydrogen sulfide and various nitrobenzenes. In general, pseudo first-order kinetics were observed, except for the initial phase of the reaction at higher pH values. Under fixed pH and Dh conditions, linear free energy relationships were found between the logarithms of the reaction rate constants and the one-electron reduction potentials of the nitroaromatic compounds. No competition was observed between various compounds. Comparison of the results of this study with the results of experiments conducted with model quinones and an iron porphyrin suggest that the secondary metabolites cinnaquinone and dicinnaquinone, excreted by strain Tu 2484 on the order of 100 mg/liter, are responsible for the catalytic activity of the exudate. Further support for this hypothesis comes from the facts that the catalytic activity of the exudate became prominent only after the growth phase of the microorganisms and that the mediating substances have a molecular weight of less than 3,000. PMID- 1622271 TI - Molecular analyses of the lactococcin A gene cluster from Lactococcus lactis subsp. lactis biovar diacetylactis WM4. AB - The genes responsible for bacteriocin production and immunity in Lactococcus lactis subsp. lactis biovar diacetylactis WM4 were localized and characterized by DNA restriction fragment deletion, subcloning, and nucleotide sequence analysis. The nucleotide sequence of a 5.6-kb AvaII restriction fragment revealed a cluster with five complete open reading frames (ORFs) in the same orientation. DNA and protein homology analyses, combined with deletion and Tn5 insertion mutagenesis, implicated four of the ORFs in the production of and immunity to lactococcin A. The last two ORFs in the cluster were the lactococcin A structural and immunity genes, lcnA and lciA. The two ORFs immediately upstream of lcnA and lciA were designated lcnC and lcnD, and the proteins that they encoded showed similarities to proteins of signal sequence-independent secretion systems. lcnC encodes a protein of 716 amino acids that could belong to the HlyB family of ATP-dependent membrane translocators. LcnC contains an ATP binding domain in a conserved C terminal stretch of approximately 200 amino acids and three putative hydrophobic segments in the N terminus. The lcnD product, LcnD, of 474 amino acids, is essential for lactococcin A expression and shows structural similarities to HlyD and its homologs. On the basis of these results, a secretion apparatus that is essential for the full expression of active lactococcin A is postulated. PMID- 1622272 TI - An enzyme immunoassay of phaseolinone and its application in estimation of the amount of toxin in Macrophomina phaseolina-infected seeds. AB - A microtiter plate-based enzyme immunoassay has been developed for phaseolinone, a phytotoxin isolated from the culture filtrate of the plant-pathogenic fungus Macrophomina phaseolina (Tassi) Goid. The smallest amount of phaseolinone detectable by the method is 5 pg per well. The method is validated by comparison with high-performance liquid chromatography and used to confirm and estimate phaseolinone production in seeds infected with the fungus. The degree of seed inhibition correlated well with the amount of toxin produced in infected seeds, 50% inhibition being observed at a toxin concentration of 0.60 micrograms/g of wet tissue. PMID- 1622273 TI - Characterization of form variants of Xenorhabdus luminescens. AB - From Xenorhabdus luminescens XE-87.3 four variants were isolated. One, which produced a red pigment and antibiotics, was luminescent, and could take up dye from culture media, was considered the primary form (XE-red). A pink-pigmented variant (XE-pink) differed from the primary form only in pigmentation and uptake of dye. Of the two other variants, one produced a yellow pigment and fewer antibiotics (XE-yellow), while the other did not produce a pigment or antibiotics (XE-white). Both were less luminescent, did not take up dye, and had small cell and colony sizes. These two variants were very unstable and shifted to the primary form after 3 to 5 days. It was not possible to separate the primary form and the white variant completely; subcultures of one colony always contained a few colonies of the other variant. The white variant was also found in several other X. luminescens strains. DNA fingerprints showed that all four variants are genetically identical and are therefore derivatives of the same parent. Protein patterns revealed a few differences among the four variants. None of the variants could be considered the secondary form. The pathogenicity of the variants decreased in the following order: XE-red, XE-pink, XE-yellow, and XE-white. The mechanism and function of this variability are discussed. PMID- 1622274 TI - Development of a gene transfer system for curing of plasmids in the marine fish pathogen Vibrio salmonicida. AB - All reported natural isolates of the marine fish pathogen Vibrio salmonicida contain plasmids, and in another marine fish pathogen, Vibrio anguillarum, it has been shown that a plasmid is important for expression of virulence by the organism. To study the function of the plasmids in V. salmonicida, we developed a gene transfer system based on the plasmid RSF1010 replicon. The gene transfer system was used to construct a plasmid-free strain, and this strain was found to behave similarly to the wild type in a fish pathogenicity test based on intraperitoneal injection of the bacteria. We were unable to detect any other phenotypic differences between the two strains. It could therefore be concluded that at least in the V. salmonicida strain tested, extrachromosomal DNA is not required for expression of virulence. PMID- 1622275 TI - Biological suppression of potato ring rot by fluorescent pseudomonads. AB - Three strains of fluorescent pseudomonads (IS-1, IS-2, and IS-3) isolated from potato underground stems with roots showed in vitro antibiosis against 30 strains of the ring rot bacterium Clavibacter michiganensis subsp. sepedonicus. On the basis of morphological and biochemical tests and fatty acid analysis, IS-1 and IS 2 were identified as Pseudomonas aureofaciens and IS-3 was identified as P. fluorescens biovar III. IS-1 was the most inhibitory to C. michiganensis subsp. sepedonicus strains in vitro, followed by IS-3 and IS-2. Suppression of ring rot by these antagonists was demonstrated in greenhouse trials with stem-cultured potato (cv. Russet Burbank) seedlings. Although each antagonist significantly reduced C. michiganensis subsp. sepedonicus populations, only IS-1 reduced infection by C. michiganensis subsp. sepedonicus. In a second experiment, treatment with IS-1 (10(9) CFU/ml) significantly reduced ring rot infection by 23.4 to 26.7% after 5 to 8 weeks. The average C. michiganensis subsp. sepedonicus population was also significantly reduced by 50 to 52%. Application of different combinations of antagonist strains was not more effective than single-strain treatment. PMID- 1622276 TI - Growth phase, cellular hydrophobicity, and adhesion in vitro of lactobacilli colonizing the keratinizing gastric epithelium in the mouse. AB - Lactobacillus strains of numerous species isolated from several animal sources exhibited cellular hydrophobicities that differed from those expected on the basis of their abilities to colonize the keratinizing stratified squamous epithelium in the mouse stomach. Cells of Lactobacillus fermentum 100-33, grown to either exponential or stationary phase, were strongly hydrophilic. By contrast, cells of L. fermentum RI and six transformant derivatives of strain RI and 100-33, strains DM101 through DM106, were hydrophobic to various degrees in either growth phase. Most of them were less hydrophobic, however, when in the stationary phase than in the exponential phase. Cells of strains RI and 100-33 in the exponential phase adhered in the same number in vitro to disks of keratinized mouse gastric mucosa. By contrast, when in stationary phase, strain RI and two transformants, DM103 and DM104, adhered to the surface in higher numbers than 100 33. In contrast to their cellular progenitor, 100-33, the transformant strains share with their DNA donor, RI, the capacity to colonize the keratinizing gastric epithelium in mice. These findings indicate that lactobacilli able to colonize the surface of the keratinocytes in the murine stomach can adhere to that surface by either hydrophilic or hydrophobic molecules. PMID- 1622277 TI - Complete biological reductive transformation of tetrachloroethene to ethane. AB - Reductive dechlorination of tetrachloroethene (perchloroethylene; PCE) was observed at 20 degrees C in a fixed-bed column, filled with a mixture (3:1) of anaerobic sediment from the Rhine river and anaerobic granular sludge. In the presence of lactate (1 mM) as an electron donor, 9 microM PCE was dechlorinated to ethene. Ethene was further reduced to ethane. Mass balances demonstrated an almost complete conversion (95 to 98%), with no chlorinated compounds remaining (less than 0.5 micrograms/liter). When the temperature was lowered to 10 degrees C, an adaptation of 2 weeks was necessary to obtain the same performance as at 20 degrees C. Dechlorination by column material to ethene, followed by a slow ethane production, could also be achieved in batch cultures. Ethane was not formed in the presence of bromoethanesulfonic acid, an inhibitor of methanogenesis. The high dechlorination rate (3.7 mumol.l-1.h-1), even at low temperatures and considerable PCE concentrations, together with the absence of chlorinated end products, makes reductive dechlorination an attractive method for removal of PCE in bioremediation processes. PMID- 1622278 TI - Incubation of water samples containing amoebae improves detection of legionellae by the culture method. AB - Some protozoans isolated from aquatic habitats, including domestic water supplies, can support the intracellular replication of autochthonous legionellae in vitro. We studied the effect of incubating water samples containing amoebae on the sensitivity of culture for legionellae. Samples collected during investigations of legionellosis epidemics and shown by conventional culture procedures to contain amoebae, but not legionellae, were incubated at 35 degrees C and replated. Legionellae were recovered from 59 of 144 such samples. Species isolated included L. pneumophila, L. anisa, L. bozemanii, L. gormanii, L. micdadei, L. rubrilucens, L. sainthelensi, L. steigerwaltii, and an unnamed species. Acanthamoeba polyphaga, Acanthamoeba hatchetti, a Rosculus sp., Hartmannella vermiformis, and Vahlkampfia spp. were among the autochthonous amoebae identified. Legionellae were recovered by this procedure from only 3 of 63 samples that were negative for amoebae by conventional culture procedures. These results show that water samples negative for legionellae, but positive for amoebae, by standard culture techniques should be incubated and replated to maximize the sensitivity of culture for legionellae. PMID- 1622279 TI - 1,3-Propanediol:NAD+ oxidoreductases of Lactobacillus brevis and Lactobacillus buchneri. AB - In the cofermentation of glycerol with a sugar by Lactobacillus brevis and Lactobacillus buchneri, a 1,3-propanediol:NAD+ oxidoreductase provides an additional method of NADH disposal. The enzyme has been purified from both L. brevis B22 and L. buchneri B190 and found to have properties very similar to those reported for the enzyme from Klebsiella pneumoniae. The enzymes required Mn2+ and are probably octamers with a molecular mass of 350 kDa. Although not absolutely specific for 1,3-propanediol when tested as dehydrogenases, the enzymes have less than 10% activity with glycerol, ethanol, and 1,2-propanediol. These properties contrast sharply with those of a protein isolated from another Lactobacillus species (L. reuteri) that ferments glycerol with glucose and previously designated a 1,3-propanediol dehydrogenase. PMID- 1622280 TI - Evaluation of the Organon-Teknika MICRO-ID LISTERIA system. AB - The MICRO-ID LISTERIA system, designed to identify Listeria isolates to species level within 24 h, was compared with conventional biochemical identification. MICRO-ID LISTERIA used in combination with the CAMP test correctly identified 409 (98.8%) of 414 strains isolated from human, animal, food, and environmental sources belonging to the seven species currently defined within the genus Listeria. The kit was easy to use and simple to interpret. However, 8 of the 15 tests (i.e., phenylalanine deaminase, hydrogen sulfide, indole, ornithine decarboxylase, lysine decarboxylase, malonate, urease, and o-nitrophenyl-beta-D galactopyranoside) were considered superfluous for the differentiation of Listeria spp. The CAMP test was indispensable when using the MICRO-ID LISTERIA system, in particular to differentiate CAMP test-positive L. monocytogenes from the nonhemolytic, rhamnose-positive L. innocua. The hemolytic L. seeligeri and L. ivanovii strains and the nonhemolytic, non-rhamnose-acidifying L. welshimeri strains could also be differentiated from one another only on the basis of their CAMP test results. The very few strains of L. grayi and L. murrayi were easily differentiated from the other nonhemolytic species. Catalase-negative cocci should not be tested, because 12 out of 19 catalase-negative strains (all enterococci) in our test were misidentified as Listeria spp. The MICRO-ID LISTERIA system identified strains within 18 to 24 h and is thus less time consuming than conventional tests. The system could, therefore, be used together with correctly done CAMP tests for the rapid identification of Listeria isolates, especially food and environmental isolates, for which rapid species differentiation is important. PMID- 1622281 TI - Utilization of cyanide as nitrogenous substrate by Pseudomonas fluorescens NCIMB 11764: evidence for multiple pathways of metabolic conversion. AB - The growth of Pseudomonas fluorescens NCIMB 11764 on cyanide as the sole nitrogen source was accomplished by use of a modified fed-batch cultivation procedure. Previous studies showing that cyanide metabolism in this organism is both an oxygen-dependent and an inducible process, with CO2 and ammonia representing conversion products, were confirmed. However, washed cells (40 mg ml-1 [dry weight]) metabolized cyanide at concentrations far exceeding those previously described; 85% of 50 mM KCN was degraded in 6 h. In addition, two other C1 metabolites were detected in incubation mixtures; their identities were confirmed as formamide and formate by 13C nuclear magnetic resonance spectrocopy, high pressure liquid chromatography, radioisotopic trapping experiments, and other analytical means. The relative yields of all four metabolites (CO2, formamide, formate, and ammonia) were shown to be dependent on the KCN concentration and availability of oxygen; at 0.5 to 10 mM substrate, CO2 was the major C1 product, whereas at 20 and 50 mM substrate, formamide and formate were principally formed. The latter two metabolites also accumulated during prolonged anaerobic incubation, suggesting that P. fluorescens NCIMB 11764 can elaborate several pathways of cyanide conversion. One is formally similar to that proposed previously (R. E. Harris and C. J. Knowles, FEMS Microbiol. Lett. 20:337-341, 1983), involving the oxygen-dependent conversion of cyanide to CO2 and ammonia. The other two, occurring in the presence or absence of oxygen, involve separate reactions to yield, respectively, formate plus ammonia or formamide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1622282 TI - Protein-mediated adhesion of Lactobacillus acidophilus BG2FO4 on human enterocyte and mucus-secreting cell lines in culture. AB - The adhesion of Lactobacillus acidophilus BG2FO4, a human stool isolate, to two human enterocytelike cell lines (Caco-2 and HT-29) and to the mucus secreted by a subpopulation of mucus-secreting HT29-MTX cells was investigated. Scanning electron microscopy revealed that the bacteria interacted with the well-defined apical microvilli of Caco-2 cells without cell damage and with the mucus secreted by the subpopulation of HT29-MTX cells. The adhesion to Caco-2 cells did not require calcium and involved an adhesion-promoting factor that was present in the spent supernatant of L. acidophilus cultures. This factor promoted adhesion of poorly adhering human Lactobacillus casei GG but did not promote adhesion of L. casei CNRZ 387, a strain of dairy origin. The adherence components on the bacterial cells and in the spent supernatant were partially characterized. Carbohydrates on the bacterial cell wall appeared to be partly responsible for the interaction between the bacteria and the extracellular adhesion-promoting factor. The adhesion-promoting factor was proteinaceous, since trypsin treatment dramatically decreased the adhesion of the L. acidophilus strain. The adhesion promoting factor may be an important component of Lactobacillus species that colonize the gastrointestinal tract. PMID- 1622283 TI - Application of DNA probes to analysis of bacteriophage distribution patterns in the environment. AB - Radiolabeled bacteriophage DNA probes have been used in this study to determine the distribution of Pseudomonas aeruginosa-infecting bacteriophages in natural samples of lake water, sediment, soil, and sewage. The sensitivity of detection of bacteriophage with the DNA probes was between 10(3) and 10(4) PFU and 10(6) to 10(7) CFU of lysogenized bacteria detectable with a homologous phage DNA probe. Analyses of environmental samples suggest that up to 40% of P. aeruginosa in natural ecosystems contain DNA sequences homologous to phage genomes. By using different bacteriophage DNA probes, the diversity of the bacteriophage population in sewage was estimated to be higher than that in other natural samples. The indication that transducing phages and prophages are widely distributed in the Pseudomonas populations investigated has considerable implications for the frequency of natural gene transfer by transduction and of lysogenic conversion of host bacteria in natural ecosystems. PMID- 1622284 TI - Temperature and structural effects on transfer of double-stranded RNA among isolates of the chestnut blight fungus (Cryphonectria parasitica). AB - Cryphonectria parasitica is a unique fungus which can serve as a model for understanding transfer of genes between eukaryotic microorganisms. We studied transfer of double-stranded RNA (dsRNA) between compatible and incompatible strains of C. parasitica to determine whether hyphal types or temperature could restrict that exchange. Hyphal connections between incompatible strains occurred at about 30% of the frequency of connections between compatible strains and differed morphologically. Gel electrophoresis and in situ hybridization confirmed that dsRNA was transferred through substrate hyphae but not through aerial hyphae. Freezing temperatures resulted in the loss of dsRNA from the new mycelium of the donor colony and stimulated the production of virulent pycnidiospores. These temperature and structural restrictions may help to explain the lack of spread of the dsRNA despite its presence in the field. PMID- 1622285 TI - An inducible, nondegradative phytoalexin resistance mechanism in Dictyostelium discoideum is suppressed by mutations that alter membrane sterol composition. AB - Pretreatment of Dictyostelium discoideum amoebae with a sublethal concentration of the pea phytoalexin pisatin was shown to induce nondegradative resistance to subsequent challenges with inhibitory concentrations. An alteration of membrane sterol composition either with the azasterol A25822B or by mutations in nysC that confer resistance to the polyene antibiotic nystatin suppressed the induction of pisatin resistance. Wild-type cells grown on pisatin medium acquired resistance to nystatin; however, after transfer to nystatin medium, they lost their pisatin resistance phenotype but remained nystatin resistant. To account for this asymmetry in the induction and maintenance of cross-resistance after growth on pisatin and nystatin media, we propose a model in which the two resistance phenotypes are governed by distinct mechanisms. This model presumes that growth on pisatin induces membrane alterations that predispose cells to acquire nystatin resistance but that the pisatin-induced membrane alterations are not maintained in the absence of pisatin. PMID- 1622286 TI - Acid adaptation promotes survival of Salmonella spp. in cheese. AB - Salmonella typhimurium was adapted to acid by exposure to hydrochloric acid at pH 5.8 for one to two doublings. Acid-adapted cells had increased resistance to inactivation by organic acids commonly present in cheese, including lactic, propionic, and acetic acids. Recovery of cells during the treatment with organic acids was increased 1,000-fold by inclusion of 0.1% sodium pyruvate in the recovery medium. Acid-adapted S. typhimurium cells survived better than nonadapted cells during a milk fermentation by a lactic acid culture. Acid adapted cells also showed enhanced survival over a period of two months in cheddar, Swiss, and mozzarella cheeses kept at 5 degrees C. Acid adaptation was found in Salmonella spp., including Salmonella enteritidis, Salmonella choleraesuis subsp. choleraesuis serotype heidelberg, and Salmonella choleraesuis subsp. choleraesuis serotype javiana, associated with food poisoning. These observations support the theory that acid adaptation is an important survival mechanism enabling Salmonella spp. to persist in fermented dairy products and possibly other acidic food products. PMID- 1622287 TI - Acquisition of a sucrose utilization system in Escherichia coli K-12 derivatives and its application to industry. AB - An Escherichia coli strain, B-62, that was isolated from a clinical source and was epidemiologically unrelated to E. coli K-12 was the source of chromosomal DNA for a sucrose utilization system (Scr+) in the construction of a plasmid, pST621. The cloned insert of a gene encoding Scr+ in pST621 conferred a sucrose-positive phenotype onto transformed cells of E. coli K-12 derivatives. Sucrase activity of the transformants was as high as that which would correspond to a "gene dosage effect" of a vector plasmid pBR322, whereas the transformants' sucrose uptake activity was always lower than that of E. coli B-62. A region within an XhoI-SacI fragment (3.2 kb) of pBR322-glyA was replaced in the construction of another plasmid, pST5R7, by a fragment (about 2.6 kb) of pST622 containing the gene encoding Scr+. A genetically stable Scr+ derivative of E. coli K-12 was obtained by introducing the gene encoding Scr+ onto E. coli chromosome via homologous recombination between pST5R7 and the chromosome and subsequent plasmid segregation. The use of low-copy-number plasmid RP4 as a cloning vector was also effective for enhancing the stability of Scr+. Tryptophan producers E. coli SGIII1032S, in which the gene encoding Scr+ was cloned onto the chromosome, and E. coli SGIII1032, which carried Scr+ plasmid RP4.5R7, produced from 6% sucrose in shake flasks (33 degrees C, 96 h) 2.3 and 5.7 g of tryptophan per liter, respectively. PMID- 1622288 TI - Thermotolerance of heat-shocked Listeria monocytogenes in milk exposed to high temperature, short-time pasteurization. AB - The effect of prior heat shock (48 degrees C for 15 min) on the thermotolerance of Listeria monocytogenes at the minimal high-temperature, short-time (71.7 degrees C for 15 s) parameters required by the Pasteurized Milk Ordinance was examined. The mean D71.7 degrees C value for heat-shocked L. monocytogenes was 4.6 +/- 0.5 s (control D = 3.0 +/- 1.0 s); the ratio of D to control D was 1.5. The increased thermotolerance of heat-shocked Listeria cells was not significant and appeared unlikely to have practical implications, in terms of risk assessment, for the safety of pasteurized milk. PMID- 1622289 TI - The family as an advocate for the mentally ill. PMID- 1622290 TI - Biological psychiatry and psychiatric nursing in America. AB - First psychiatry and then psychiatric nursing have moved into an era of psychobiology. In many cases, psychiatric nurses are leaving behind their appreciation of the mind-body-brain connection in favor of a purely biological approach to the etiology and treatment of mental illness. This article is an attempt to show the interrelatedness of these concepts and includes a clinical case example of an "endogenously" depressed man who was treated for a period of 15 years. PMID- 1622291 TI - Researching and evaluating model geriatric mental health programs. Part III: Statistical analysis issues. AB - The third and final article in this three-part series on researching and evaluating geriatric mental health programs focuses on statistical analysis issues. Analysis of data from experimental and quasi-experimental studies is discussed involving inferential statistical techniques such as t test, analysis of variance, chi-square, and analysis of covariance, and interrupted time series techniques. PMID- 1622292 TI - Nurses as patient assault victims: an update, synthesis, and recommendations. AB - The literature documenting the incidence and reactions of nursing staff who have been assaulted by patients is increasing. Before 1980 very little work was done in the area. What did appear generally indicated that patient violence against staff was infrequent, and on the rare occasion when it did occur the staff member was usually in some way responsible. Current research shows that assault is a serious risk factor for nurses. The incidence of assault is high and vastly underreported. Staff members experience short- and long-term emotional, social, biophysiological, and cognitive reactions to being assaulted. Interventions to help the staff victim in the recovery process are increasingly used. PMID- 1622293 TI - Sense of belonging: a vital mental health concept. AB - Sense of belonging is a concept that has not been researched in psychiatric nursing practice. Using a concept-analysis strategy proposed by Walker and Avant, the authors present a detailed description of the concept that evolved from a series of inductive and deductive strategies. Sense of belonging is defined as the experience of personal involvement in a system or environment so that persons feel themselves to be an integral part of that system or environment. Sense of belonging has important applicability for clinical use as well as continued theory development in psychiatric nursing. PMID- 1622294 TI - Self-destructive and impulsive behavior in the patient with a borderline personality disorder: rethinking hospital treatment and management. AB - This article reconsiders current approaches to the inpatient treatment and management of the patient with a borderline personality disorder. It is suggested that current approaches tend to be reactive rather than proactive. An alternative model based on a behavioral therapy program for chronic parasuicidal borderline women, is suggested. The approach reframes self-destructive behavior as a habitual response to overwhelming affect. By targeting core problems such as self destructive and impulsive behaviors, nurses can help patients begin to consider alternative behavioral responses to intense stress. PMID- 1622295 TI - Maintenance of therapeutic community principles in an age of biopharmacology and economic restraints. AB - The therapeutic community has changed significantly since its development in England more than 40 years ago. However, the hallmarks of the therapeutic milieu, such as patient participation in decision making, a multidisciplinary staff, and a belief that the environment is the treatment agent, remain part of many psychiatric settings. The therapeutic community will continue to undergo alteration to adapt to changes in society. It will continue to be a viable treatment modality as long as the value system of the organizational culture and the internal structure of the community are included as basic concepts. Systems theory and organizational culture concepts are used to explore the factors that enhance the functioning of a therapeutic community in an era of biological treatment and rising health care costs. PMID- 1622296 TI - Overcoming stigmatization: social and personal implications of the human immunodeficiency virus diagnosis. AB - All diseases have attached metaphors. Social and personal reactions to people with human immunodeficiency virus are influenced by the metaphor, "fear of polluting people," and have in common with sexually transmitted diseases, the irrational fear of easy contagion. These issues negatively affect clients' response to their diagnosis and their treatment and care. Many clients have suffered as a result of receiving care from professionals who are condemning of the person with the disease. Others, though have found supportive care givers and have experienced positive reactions to the diagnosis through achieving emotional and spiritual development. The response of nursing to this stigmatized disease is explicated. PMID- 1622297 TI - An examination of factors influencing the diagnosis and treatment of black patients in the mental health system. AB - The Civil Rights Movement, which began in the 1950s and lasted through the mid 1970s played a major role improving the quality of life for black Americans. Although much has changed since the 1950s the roots of racism are deep and change occurs slowly. Race exerts an overwhelming influence on popular ideology and medical thinking. Many researchers have speculated that a strong association exists between race and diagnosis. Understanding the sociocultural background of the patient would aid in the distinguishing culturally bound behavior from behavior that reflects actual psychopathology. This review examines the professional literature on racial and ethnic factors as they pertain to the diagnosis and treatment of black patients in the mental health system. PMID- 1622298 TI - Applying psychometric criteria to functional assessment in medical rehabilitation: II. Defining interval measures. AB - The use of functional assessment total scores in arithmetic operations has proliferated despite the lack of evidence supporting their use as interval measures of patient ability. Such evidence is minimally necessary to assure the validity of functional assessment total scores for clinical and management decision-making. Two requirements of interval measurement are explained and a set of Rasch analyses of 5,500 assessments using the Patient Evaluation and Conference System (PECS) are presented. The analyses were performed to determine the extent to which four item subsets identified in a previously reported factor analysis of the PECS comprise interval measures of functional independence status. Results indicate that the PECS scales meet these requirements to varying degrees. The analyses also identify areas in which measurement quality can be improved. PMID- 1622299 TI - Quantifying handicap: a new measure of long-term rehabilitation outcomes. AB - According to the World Health Organization (WHO), handicaps exist when individuals are unable to fulfill expected social roles. Although ameliorating handicaps is one of the prime goals of rehabilitation, its effectiveness in this area is poorly measured and has not been documented empirically. Therefore, the Craig Handicap Assessment and Reporting Technique (CHART) was designed to quantify the extent of handicap in individuals. Using dimensions of handicap identified and described by the WHO, CHART uses measurable, behavioral terms to compare such individuals with the norms of able-bodied members of society. Test retest, proxies, and independent raters have established the validity and reliability of CHART. Rasch analysis has verified the CHART scaling and scoring procedures. In addition, an initial application of CHART, with a group of 342 spinal cord injured individuals, is described. Beyond demonstrating the instrument's effectiveness in assessing the extent of handicap or social disadvantage, this application, by documenting rehabilitation outcomes, demonstrates the potential usefulness of CHART for program evaluation. PMID- 1622300 TI - Upper extremity functional assessment scales in children with Duchenne muscular dystrophy: a comparison. AB - Twenty-three subjects were assessed using the already established Brooke Upper Extremity Functional Rating Scale and the timed Jebsen Hand Function Test to determine whether the Jebsen test was a more discriminative measure of upper extremity function in patients with Duchenne muscular dystrophy (DMD). The data were analyzed using univariate and forced-entry multiple regression analyses to determine the relationship between the Jebsen and Brooke scales while removing the effects of the other independent variables: age, hand dominance, and visit number. The univariate regression results suggested a positive relationship between the Brooke and Jebsen scales. Discrete sublevels of time on the Jebsen Hand Function Test were not found within the Brooke functional levels. However, the Jebsen test was found to be a more sensitive assessment of hand function than the Brooke scale among the DMD population. Parametric data were gathered, nondominant and dominant hand functions were differentiated, and a constant set of muscle groups was used to complete the tasks of the Jebsen Hand Function Test. The Jebsen Hand Function Test might be used instead of the Brooke scale as a more discriminative method of following DMD patient progress over time, both clinically and during drug treatment trials. PMID- 1622301 TI - Validity and reliability of a hand-held dynamometer applied to adults with mental retardation. AB - The purpose of this study was to determine the validity and reliability of the Nicholas Manual Muscle Tester (MMT) as applied to ten adults with mild to moderate mental retardation between the ages of 18 to 39 years with an intelligence quotient (IQ) range of 36 to 69. Using stabilization techniques, isometric torque values were taken of knee extension and elbow flexion on separate days with the Nicholas MMT and a Cybex II dynamometer. Pearson product moment correlations of these two instruments ranged from .64 to .76 (p less than 0.05). Based on 1 day of testing intrarater correlation coefficients for the Nicholas (MMT) ranged from .97 to .99 (p less than 0.05). In like fashion interrater generalizability coefficients were quite high (G = .97 - 98). Measurements of adults with mental retardation taken by two experienced evaluators with a Nicholas MMT seem to evaluate the component-isometric strength. Highly reliable measurements with stabilization techniques were obtained with this instrument. PMID- 1622302 TI - Severity of pediatric traumatic brain injury and early neurobehavioral outcome: a cohort study. AB - Traumatic brain injury (TBI) is a major cause of pediatric disability. Its neurobehavioral sequelae can often be difficult to distinguish from premorbid problems. To establish the early neurobehavioral consequences of TBI, we compared a cohort of brain injured children with controls, individually matched on premorbid characteristics. Ninety-eight children, aged 6 to 15 years, with mild, moderate, and severe closed head injuries, were consecutively identified on presentation to two regional medical centers. Individually selected controls were matched for age, gender, school grade, behavior, and academic performance. Intellectual, neuropsychologic, and academic assessments were undertaken 3 weeks after full orientation was achieved. No significant case-control differences were found on 20 variables measuring premorbid status. The pattern of decline in performance with increasing severity of brain injury was consistent for measures assessing intelligence, memory, speeded motor performance, adaptive problem solving, and academic performance. Moderately and severely injured patients performed at normal levels in reference to standardized intellectual norms, but they showed impairment when compared with their matched controls. The impairments uncovered in this study place moderately and severely brain injured children at risk for problems in the acquisition of academic skills and higher-order cognitive abilities. PMID- 1622303 TI - Factors influencing reintegration to normal living after amputation. AB - This study identified factors affecting reintegration to normal living (RNL) after lower extremity amputation. A questionnaire was used to evaluate RNL at a veterans' medical center and private rehabilitation clinic. The patients were 42 elderly individuals (68 +/- 1.5 years). Eighty-eight percent were men and 76% had additional health problems. Unilateral below-knee amputations, unilateral above knee amputations, and bilateral amputations accounted for 38%, 36%, and 26% of subjects, respectively. Eleven questions were asked to evaluate mobility, self care, work, recreation, social activities (daily functioning), relationships, social self, and life events (perception of self). The median overall RNL score was 16 of 22 (range, 5 to 22). Poor reintegration occurred in community mobility, work, and recreation. Perception of self questions showed satisfactory reintegration. Examination of variables impacting reintegration showed only additional illness significantly reducing the RNL score. It was concluded that current rehabilitative efforts regarding home mobility and psychological adjustment are satisfactory. More attention to community mobility, recreation, and additional illnesses would improve RNL after amputation. PMID- 1622304 TI - Relationship of life satisfaction to impairment, disability, and handicap among persons with spinal cord injury living in the community. AB - The level and correlates of the life satisfaction of persons with spinal cord injury who are residing in the community were investigated. One hundred men and 40 women were chosen randomly from a cohort of 640 persons with spinal cord injury residing in a 13-county area in southeast Texas. The mean Life Satisfaction Index-A (LSIA-A) was lower than reported previously for persons in the general population. The LSIA-A was not correlated significantly with chronologic variables, the ASIA Total Motor Index Score, or a self-report version of the Functional Independence Measure. The LSIA-A was associated positively with self-assessed health, perceived control, and social support, as well as with the Social Integration, Occupation, and Mobility dimensions of the Craig Handicap Assessment and Reporting Technique. From the standpoint of an augmented version of the World Health Organization model of disablement, the life satisfaction of persons with spinal cord injury appears to be influenced, albeit indirectly, by selective aspects of their social role performance (handicap), but not by their degree of impairment or disability. PMID- 1622305 TI - Mortality after spinal cord injury: a four-year prospective study. AB - Research has suggested that mortality after spinal cord injury (SCI) is correlated with lower levels of social and vocational activities and lower life satisfaction. The purpose of this study was to use prospective data from a 1985 SCI follow-up study to identify predictors of survival status four years later. In 1985, responses to the revised Life Situation Questionnaire were obtained from 347 participants with SCI. Survival status was ascertained in 1989; 89% (n = 309) were known to be alive and 6% (n = 22) were deceased. Multivariate ANOVA was used to compare the surviving and deceased participant groups using the 1985 data. Results suggested that survivors had superior adjustment on many of the variables tested in 1985. In particular, the survivors were more active, rated their adjustment as better, were more satisfied with many areas of life, and reported fewer problems (especially with emotional distress). Recent medical history (ie, nonroutine doctor visits and hospitalizations) was not related to survival. This study reaffirms the importance of psychologic, social, and vocational variables as predictors of survival. A call is made for rehabilitation psychologists to address tough issues (eg, substance abuse) and to thoroughly study more specific health behaviors as they relate to survival after SCI. PMID- 1622306 TI - Longitudinal changes in adjustment after spinal cord injury: a 15-year study. AB - Research on changes in adjustment after spinal cord injury (SCI) has produced mixed results. Whereas cross-sectional research has suggested that adjustment declines with increasing age, but improves with greater time since injury, longitudinal research has suggested that some limited positive changes in adjustment occur over an 11-year period. The purpose of the current study was to identify the stability of adjustment over a 15-year period after SCI. One hundred thirty-five participants with SCI completed Life Situation Questionnaires (LSQ) in both 1974 and 1989. T-test comparisons were made on five adjustment scales and 15 individual items. The results suggested several positive changes in adjustment during the 15 years including increased sitting tolerance, more years of education, greater satisfaction with finances and employment, and a higher percentage of persons working. Decreases were noted in the number of hospitalizations and the number of days hospitalized. Given the average number of years since injury (9.3 years in 1974; 24.3 years in 1989), the results suggest that adjustment will at worst be stable, and at best will improve significantly with time. PMID- 1622307 TI - Postural organization in patients with hereditary motor and sensory neuropathy. AB - The postural organization in patients with hereditary motor and sensory neuropathy (HMSN) type I or II was studied clinically by means of a force platform. Balance was registered in 14 barefooted HMSN patients and healthy matched control subjects during quiet stance. The effect of visual deprivation was tested to determine the degree of visual dependency. The effect of the simultaneous performance of a concurrent attention-demanding task (Stroop task) was tested to estimate the level of balance automaticity. In comparison with control subjects, the HMSN patients showed a basically decreased efficiency of postural control (p less than .01) as well as an increased visual control of posture (p less than .05) in both directions of sway. No loss of balance automaticity was found, which suggested an on-line central adaptation to the slowly developing peripheral impairments. The results provide a starting point for understanding the balance problems and gross motor disabilities in HMSN patients. PMID- 1622308 TI - Social support intervention after stroke: results of a randomized trial. AB - The purpose of this study was to determine if social support intervention would improve the support experienced by stroke survivors and if improvement would result in better psychosocial outcome. Subjects were drawn from a community-based sample that had received rehabilitation services in the hospital and at home. The study was a randomized trial (n = 48 experimental group, n = 40 control group), and measures were taken at entry into the study, immediately after intervention (or, at a comparable time for the control group), and again 3 months later. No significant differences were found between groups either on social support measures or psychosocial outcomes. Secondary analyses showed that significant changes in support had been experienced within the sample as a whole in relation to the subjects' gender, living situation, marital status, and employment status. Findings are discussed in terms of methodologic and programmatic concerns, and recommendations are made for further research with this potentially valuable intervention. PMID- 1622309 TI - Geriatric rehabilitation: perspectives from the United Kingdom. AB - Although rehabilitation professionals acknowledge the need for more services for the aging American society, only recently has there been large-scale discussion on the state of geriatric rehabilitation in the United States. In contrast, geriatric rehabilitation has been a central component of British health planning since the beginning of the National Health Service in 1948. In the hope of stimulating discussion, this article examines geriatric rehabilitation services in the United Kingdom. Contrasts between the UK and US are drawn to highlight the relative strengths and weaknesses of each system of care. The importance of cultural determinants to health care services is emphasized. PMID- 1622310 TI - Emotional dysfunction in a geriatric population: staff observations and patients' reports. AB - This study was designed to determine the following about a geriatric rehabilitation population: (1) the relationship between patients' self-reports of depression and anxiety and staff observations of compromised participation in treatment secondary to emotional dysfunction; (2) the relationship of observations among different disciplines; and (3) changes that may occur to staff observations during the patient's hospitalization. The Geriatric Depression Scale, the depression and anxiety subtests of the Brief Symptom Inventory, and the Modified Mini-Mental State Exam were administered to geriatric patients on admission to and discharge from two DRG-exempt acute rehabilitation units. In addition, day nurses, evening nurses, occupational therapists, and physical therapists rated the same geriatric patients on how frequently their emotional functioning interfered with rehabilitation. Significant correlations were obtained between staff observations and patients' reports of emotional dysfunction, with occupational therapists' ratings generally the most highly correlated with patients' reports. At admission, day and evening nurses reported significantly greater patient emotional dysfunction than did occupational therapists, who reported significantly greater emotional dysfunction than did physical therapists. These differences, however, were not evident by time of discharge. Thus, staff members can provide reliable information to mental health professionals in determining the effect of emotional functioning on rehabilitation participation. However, level of compromised participation secondary to emotional dysfunction reported by staff appears to be contingent on which rehabilitation discipline is asked and when during the patient's hospitalization the inquiry is made. Also, patients who generally participated less in treatment tended to be older, depressed women with less education and greater cognitive impairment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1622311 TI - Spontaneous coping strategies to manage acute pain and anxiety during electrodiagnostic studies. AB - Electrodiagnostic studies produce both anxiety and pain, which can prevent adequate examination and limit the usefulness of test results. This study examined the spontaneous coping strategies used to manage the pain and anxiety experienced during electrodiagnostic testing. Fifty patients (26 women and 24 men) evaluated in our electrodiagnostic laboratory were administered visual analogue scale (VAS) pain and anxiety measures and the Spielberger State-Trait Anxiety Inventory (STAI) before the procedure. Immediately after the procedure, subjects reported pain, anxiety, and coping strategies used during electrodiagnostic testing using the VAS, the STAI, and a situation-specific version of the Coping Strategies Questionnaire (CSQ-S). The CSQ-S appears to be a valid and reliable measure of spontaneous coping strategies. Multiple-regression analyses revealed that frequent use of catastrophizing, diverting attention, and coping self-statement strategies was significantly and positively correlated with pain, whereas reinterpreting pain was significantly and negatively associated with pain. Judgments of control over pain were also significantly and negatively associated with anxiety experienced during electrodiagnostic studies. Physicians' ratings of pain and anxiety were highly correlated with patients' self-reports. This study suggests that ineffective coping strategies may enhance the pain and anxiety experienced during electromyography. Alternatively, teaching subjects active self-control skills and increasing patients' self-efficacy beliefs may help manage this situation-specific acute anxiety and, possibly, the associated pain. PMID- 1622312 TI - Coronal computerized tomography and cerebrospinal fluid rhinorrhea. AB - Accurate diagnosis of cerebrospinal fluid rhinorrhea (CSFR) is a challenge for physicians caring for patients with traumatic brain injury. Failure to recognize this condition may result in significant medical complications and prolong hospitalization. Two male patients who developed CSFR within 2 months of severe head injury are described. A clear nasal discharge was noted on examination approximately 30 and 35 days after head injury in both patients and a CSF fistula was suspected. High-resolution computerized tomography (CT) with coronal sections confirmed the diagnosis. Both patients underwent neurosurgical intervention to repair the fistulous tracts without recurrence. Sequelae of CSFR in one case included meningitis and pneumocephalus. Literature review shows water-soluble contrast CT cisternography (CTC) to be the gold standard for the diagnosis of CSFR. However, other diagnostic studies may include immunoelectrophoresis of rhinorrhea, use of isotope tracers, plain x-rays, tomography, and noncontrast high-resolution CT. More invasive studies like CTC are often recommended in the diagnosis of this condition, but are more costly, painful, and carry a small risk of infection. Our two case reports emphasize that high-resolution CT may be performed as a primary noninvasive diagnostic procedure before more invasive studies, and the results obtained may be sufficient for therapeutic planning. PMID- 1622313 TI - Physical training effects on the fitness and habitual activity patterns of elderly women. AB - This study investigated the effect of a twice-weekly, six-month progressive walking program on 80 healthy women aged 60 to 70 years. Aerobic fitness, blood pressure, skinfold thickness, spirometric variables, and activity profile were studied. No significant differences existed between the training group (TG) and the control group (CG) at the commencement of the study. However, after 26 weeks of training, the TG registered significantly lower heart rates than the CG, both at rest (p = .019) and during the five to six minutes of an ergometer work test (p = .003). A Mann-Whitney U test on the difference scores (26 weeks-0 week) indicated higher scores for the TG compared with the CG for Maximum Current Activity (p = .001) and Normative Impairment Index (p = .002), which are both components of the Human Activity Profile. These data suggest that adherence to a low-frequency training program can elicit positive physiologic changes in elderly women. Furthermore, increased habitual activity patterns are likely to be indicative of improvements in functional ability, lifestyle, and independence. PMID- 1622314 TI - Biomechanical analysis of the sit-to-stand motion in elderly persons. AB - The sit-to-stand motion of ten healthy subjects, 65 to 76 years old, was evaluated using kinematic, force plate, and electromyographic data to characterize the sit-to-stand motion. Kinematic data collected by video, muscle activity monitored by surface electromyography, and ground reaction forces analyzed by a piezoelectric force plate were used for analysis. Using these synchronized data, three phases of the sit-to-stand motion were identified--phase 1, weight shift; phase 2, transition; and phase 3, lift. A consistent pattern of trunk and lower extremity motion was observed, and two distinct upper extremity movement strategies were identified. The onset of muscle activity occurred in the following order: erector spinae, rectus femoris, and vastus medialis (phase 1); biceps femoris, gluteus maximus, and rectus abdominus (phase 2). This characterization of the sit-to-stand motion for a small population of healthy elderly subjects serves as a basis for identifying problems in elderly patients who demonstrate difficulty getting up from a chair. PMID- 1622315 TI - Sensory root level recovery in patients with Frankel A quadriplegia. AB - This prospective study was designed to demonstrate root level recovery of sensation in the zone of partial preservation in patients with C4 through C8, Frankel A spinal cord injuries. Subjects were evaluated for pin (n = 18) and light touch (n = 17) sensation. All subjects had normal sensation at the level of injury, and decreased or absent sensation at all levels caudal to that level within the zone of partial preservation; they had absent sensation at all levels below the zone of partial preservation. After the initial examination, patients were evaluated weekly for four weeks, and then at 2, 3, 6, 12, 18, and 24 months postinjury. Six of 18 patients recovered pin sensation and five of 17 recovered light touch within three months of injury. Most subjects who recovered had injuries from C5 through C8. Eleven of 12 C4 patients did not recover pin sensation, and 11 of 11 failed to recover light touch. However, five of six C5 to C8 patients recovered both pin and light touch. The p values (Fisher-Exact tests) for the C4 vs C5 to C8 groups were .004 and .001 for pin and light touch, respectively. In conclusion, approximately 30% of the total population improved one sensory root level, with the C5 to C8 injured patients comprising the majority of this improvement. PMID- 1622316 TI - Hypoxia episodes during sleep in high tetraplegia. AB - To determine whether oxygen desaturation occurs during sleep in high tetraplegics, 10 neurologically stable male patients (aged 17 to 55 years) with complete motor lesions (C4 to C6) had continuous pulse oximetry recordings and sleep observations on two nights. The patients were studied during admissions for nonrespiratory problems (eg, pressure sores, urinary infection, respite). Lung function tests and daytime arterial blood gases were also measured. Mean forced vital capacity was 46% of predicted, but mean awake PaO2 and PaCO2 were normal (95.0 mmHg and 42.8 mmHg, respectively). Three subjects showed severe nocturnal oxygen desaturation spending greater than 10% of the time overnight with arterial oxyhaemoglobin saturation (SaO2) levels of less than 90%. For the group as a whole, the percentage of time spent under 90% SaO2 correlated with body mass index. Mean overnight SaO2 correlated inversely with body mass index and directly with maximal expiratory pressure, a measure of respiratory muscle strength. Low overnight SaO2 was also associated with higher levels of injury. The pattern of nocturnal oxygen desaturation observed was episodic and was suggestive of obstructive sleep apnoea during rapid eye movement (REM) sleep. Levels of nocturnal oxygen desaturation similar to those observed in the three most severely affected patients have been shown, in other disorders, to be associated with cognitive impairment, cardiovascular disease and increased mortality. Our results suggest up to a third of high tetraplegics may be at risk of potentially serious nocturnal hypoxic episodes. PMID- 1622317 TI - Evaluation of coma and vegetative states. AB - The Coma/Near-Coma (CNC) scale was designed to measure small clinical changes in patients with severe traumatic and nontraumatic brain injuries who were functioning at very low levels characteristic of near-vegetative and vegetative states. In 20 patients followed for 16 weeks the scale identified 25% who ultimately showed modest improvement. Interrater reliability was high (r = .95); validity was supported by significant correlations between CNC- and brain multimodality evoked potential abnormality scores as well as between scores on the CNC and the Disability Rating Scale. The CNC scale was easily learned and it could be completed quickly and cost effectively. Staff found it useful in recognizing among relatively homogeneous low-level patients those most likely to respond to further rehabilitation care. The CNC appears to be useful for justifying ongoing intensive rehabilitation and for preventing premature transfer to lower levels of care. PMID- 1622318 TI - Early intervention in severe head injury: long-term benefits of a formalized program. AB - With traumatic brain injuries numbering more than two million per year, health professionals are faced with the challenges of restoring and maximizing quality of life. This study quantifies the benefits of a formalized head injury program, including the concept of trauma rehabilitation, defined as early, aggressive rehabilitation during acute hospitalization. Thirty-eight severely head injured patients received treatment at the same rehabilitation facility. Twenty-one of these patients received acute care services at ten different hospitals without formalized traumatic brain injury programs, and 17 received services at a hospital with a formalized early intervention program. Comparison of outcome data for the two programs revealed that patients in the formalized program had comas and rehabilitation stays approximately one third the length of patients in nonformalized programs (18.9 vs 53.8 days and 106.5 vs 239.5 days, respectively). Mean cognitive levels at discharge from the acute hospitals (5.6 vs 4.0) and the rehabilitation facility (7.4 vs 6.7) were significantly higher for the formalized program, and they facilitated a significantly higher percentage of discharges to home vs extended care facility (94% vs 57%). PMID- 1622319 TI - Value of gait analysis in the assessment of surgery in cerebral palsy. AB - Twenty-three ambulatory children with cerebral palsy were assessed preoperatively by a detailed clinical examination and by gait analysis using a video-based gait analysis system (VICON). Surgery was then performed based on either the clinical assessment alone or a combination of clinical evaluation and gait analysis. About one year after surgery, a postoperative clinical and gait analysis assessment was performed. Sixteen children had improved and seven children had not improved after surgery. Most of the children who had not improved were found to have had operations that differed from those recommended by gait analysis. Dynamic EMG studies were found to be useful in preoperative planning but did not show any consistent improvement even in the children with good results. The combination of a careful clinical assessment and gait analysis can produce better results in surgery for children with cerebral palsy. PMID- 1622320 TI - Effect of lower limb on body propulsion. AB - The purpose of this study was to analyze and compare the effects of the leg during swing and stance phases of forward propulsion of the body for both men and women. Twelve able-bodied subjects, six men and six women, were studied with a Vicon(a) gait-analysis system. A two-dimensional, sagittal-plane biomechanical analysis featuring a link-segment model was used to determine the force at the hip in the horizontal direction. Integrating this force curve over time during the swing and stance gait phases produced linear impulses, representing swing and stance contributions to the propulsion of the body, and it allowed quantitative comparisons using student t and Fisher tests. The deceleration of the swing leg was found to be the major contributor to the forward propulsion of the body. The stance leg initially exerted the major restraining or negative impulse during early stance; then it generated a positive impulse during push-off in late stance. A typical pattern of gait impulses was defined for normal gait. Male and female gait impulses were not significantly different for all gait phases. PMID- 1622321 TI - Complications of intracavernous injections and penile prostheses in spinal cord injured men. AB - Erectile dysfunction is a common complication in men who have had spinal cord injury (SCI). This retrospective study focuses on the complications encountered at our institution with both penile prostheses and intracavernous injections in men with SCI. Seventy-two men with SCI were treated with intracavernous injections for erectile dysfunction, and 30 penile prostheses were implanted in 19 men with SCI. Twenty-two of the 72 patients in the intracavernous injection program had adverse effects; none were severe. Prolonged erections lasting four to six hours and ecchymosis were the most common complications. No complication required discontinuation of treatment. There were 23 inflatable prostheses and seven semirigid rods. Mechanical failures occurred in 15 instances, infection occurred in nine, and late erosion occurred in three. Although multiple revisions and replacements were necessary, 14 of the 19 patients had satisfactorily functioning implants at their last outpatient visit. Patients were selected carefully for penile implant placement and yet significant complications and expense were incurred to obtain satisfactory results. Although follow-up has been relatively short, the intracavernous injections of vasoactive medications appear to be a more attractive initial means of treating the erectile dysfunction in men with SCI. The complications are relatively minor and the incidence of prolonged erections has decreased with increased experience. Furthermore, the cost of treatment will be considerably less than that with implant surgery, particularly in view of the high drop-out rate. Although improved implants have decreased the occurrences of mechanical failure, it seems likely that infection and extrusion will continue to be significant problems among men with SCI. PMID- 1622322 TI - Low-dose ultrasound effects on wound healing: a controlled study with Yucatan pigs. AB - This study reports on the effect of low-dose ultrasound in accelerating wound healing in matched pairs of surgically induced incisions and full-thickness and partial-thickness lesions in 11 Yucatan mini-pigs after 7 days of healing and 5 days of sonation. Tensile strength, collagen deposition (hydroxyproline), reduction in wound size (full-thickness lesion), and mast-cell degranulation were significantly greater in the sonated lesions than in the sham-treated controls (p = 0.01). Sonation enhanced strength by 24% and collagen deposition by 29%, when compared with controls. There were no significant differences in the quality of healing as measured by an ordinal scale. The results suggest that within the first week of healing, low-dose ultrasound facilitates wound healing. More research is needed to confirm the most effective dose, frequency, and treatment duration and intervention time for maximum healing. PMID- 1622323 TI - Functional electric stimulation: its efficacy and safety in improving pulmonary function and musculoskeletal fitness. AB - The efficacy and safety of functional electric stimulation (FES) in improving cardiovascular and musculoskeletal fitness in individuals with spinal cord injury was evaluated. Ten males and two females aged 16 to 46 years began an FES program from three months to 22 years after injury. Seven patients had paraplegia and five had quadriplegia. The FES protocol consisted of three phases: (1) leg extension, the stimulation of the quadriceps muscle group only, first without and then with weights; (2) ergometry, the stimulation of quadriceps, hamstrings, and gluteal muscles to produce a bicycling motion; and (3) resistance, the addition of resistance during the bicycling motion described in phase 2. Values for tidal volume, oxygen consumption, and the respiratory quotient were obtained during each phase. Tidal volume and oxygen consumption levels increased significantly (p less than .001) from the start of FES to both the ergometry and the resistance phases. The respiratory quotient improved significantly (p less than .001) from the start of FES to resistance but not from the start of FES to ergometry. Thigh and calf girths were measured at the start of FES and during resistance. Thigh girths increased significantly from the beginning of the program to the resistance phase, p less than .002 for the right leg and p less than .001 for the left. Calf girth, however, showed no significant increase. Based on these improvements and the absence of any serious complications, we believe that FES is an effective and safe method to improve cardiovascular and musculoskeletal fitness in individuals with spinal cord injury. PMID- 1622325 TI - Anger management training for brain injured patients and their family members. AB - Anger dyscontrol is a common occurrence after brain injury. The anger problems of brain injured persons create a burden for their caretakers who most frequently are their family members. Two single-case design studies are presented that demonstrate the efficacy of behavioral interventions for the control of anger problems in brain injured adults. Anger control was accomplished by training the patients in skills to control their own anger, and teaching family members behavior modification principles. In each case, the patient was taught to implement a self-talk method to decrease tension during the escalation period of an anger episode and to execute a time-out when aware of increased anger. Family members were trained in ways to monitor such problems and to identify antecedents to an outburst. They were given feedback and suggestions to modify their communication style with the patient so as to reduce patient irritability, and were taught ways to use a verbal cue to remind the patient to use pretrained self control methods. Patients and family members were also asked to increase the number of pleasant events in which they engaged as a general means to decrease the patients' anger outbursts. These cases showed evidence that the treatment program reduced the frequency of anger outbursts and, in one case, increased the social participation by the patient immediately after treatment and at one-month and three-month follow-up assessments. The importance of having key family members involved in anger management training for brain injured patients is underscored, particularly when cognitive impairment limits patients' ability to benefit from and to retain the content of psychotherapy. PMID- 1622324 TI - Interdisciplinary management of hemicorporectomy after spinal cord injury. AB - Hemicorporectomy (HCP) is infrequently used, but its effects can devastate the patient's body image, autonomic function, and physical abilities even more than a spinal cord injury of comparable level. Interdisciplinary management is of the utmost importance. This report describes the 2 year course, including four separate rehabilitation admissions, of a patient who was initially paraplegic, and then underwent a HCP for complications secondary to a cauda equina ependymoma. The patient's expectations for functional independence were established by his successful initial spinal cord rehabilitation. The HCP was performed 6 months after initial discharge secondary to infected Harrington rods and rapid spread of the tumor. Extensive use of the interdisciplinary team approach allowed comprehensive analysis and treatment of the patient's comfort, mobility, skin tolerance, and upper extremity functional abilities. Four successive prostheses were developed and modified, until all concerns were successfully addressed. The patient ultimately became completely independent at the wheelchair level. The evaluations, treatment plan, and emphasis of each discipline, including physical therapy, occupational therapy, rehabilitation nursing, therapeutic recreation, social work, vocational rehabilitation, and physiatry are summarized. Differences between the patient's course and standard spinal cord rehabilitation are detailed. PMID- 1622326 TI - Laryngeal diversion in the treatment of intractable aspiration in motor neuron disease. AB - Motor neuron disease/amyotrophic lateral sclerosis (MND/ALS) often causes bulbar palsy with subsequent aspiration. Laryngeal diversion procedures are not commonly mentioned in the literature. However, they are viable but infrequently used surgical treatment options that have several advantages over a routine tracheostomy. We report a case of a 67-year-old man with MND/ALS and severe aspiration. He underwent a laryngeal diversion procedure with complete relief of signs and symptoms of aspiration. Laryngeal diversion, unlike tracheostomy, completely eliminates the possibility of aspiration as well as the need for suctioning. The primary disadvantage is complete loss of phonation. These procedures appear worthy of trial in patients with MND/ALS, and may ultimately be the preferred treatment in this setting. PMID- 1622327 TI - Evaluation of a vocational robot with a quadriplegic employee. AB - A vocational robotic workstation capable of performing activities of daily living (ADL) and vocational tasks was placed for 18 months in the work site of an employee with C4 to C5 quadriplegia. A single-subject study was conducted to evaluate the performance of the robot vs that of a human attendant. The employee preferred the robot over the attendant for performance of all vocational tasks and ADLs, with the exception of feeding. Results indicated that the robot was capable of safely replacing the attendant for two five-hour periods during the workday, thus proving to be a cost-effective alternative to full-time, on-the-job attendant care. The study demonstrated the potential of robotics technology for returning independence and control to disabled employees and for offering corporate employers a solution to the problem of reasonable accommodation in the workplace. PMID- 1622328 TI - Cervical flexor strength. PMID- 1622330 TI - [Outbreaks of asthma attack and meteorological parameters--comparison between two areas]. AB - The correlation between patient visits and meteorological parameters were analyzed regarding asthmatic children who visited the outpatient emergency clinics at Teikyo University Hospital in Tokyo and Ogaki Municipal Hospital in Gifu, during the two years of 1986 and 1987. The yearly climatological changes are quite similar in both areas. Moreover, variations in the number of patient visits were also remarkably similar in both areas. High temperatures and high vapor pressure significantly correlated with increased numbers of visits in both areas. High humidity and high barometric pressure had some correlation with increased numbers of visits in both areas. As for wind direction, northerly synoptic winds had a significant correlation with increased numbers of visits in Tokyo, while contrarily, southerly winds produced the same effect in Ogaki. Precipitation and cloud density showed no correlation with the number of patient visits in either area. PMID- 1622329 TI - [Standardization of allergens]. PMID- 1622331 TI - [Infection and asthma. V. Study of childhood asthma and viral infection by cytological analysis of nasal smears]. AB - Cytological analysis of nasal smears was carried out for 295 asthmatic children aged 2 to 15 years old at the time of asthma attack and non-attack, in combination with blood tests and chest roentgenograms. Damaged ciliated cells (ciliocytophhthoria, CCP) were looked for as a marker of viral infections. The appearance rate of greater than 2+ of CCP was higher among children during attack (38/70, 54.3%) than that among children not suffering an attack (6/29, 20.7%); this was pronounced among young children under five. However, the results of blood examinations and chest roentgenograms did not correlate with the rate of positive signs of infections in CCP positive- or negative-attack. These results suggest that the cytological examination of nasal smears in useful in evaluating the presence of viral infections during asthma aggravation among young children, whereas evaluation of these infections may be difficult by blood tests or chest roentgenograms. PMID- 1622332 TI - [Asthma classification by score calculated from clinical findings and examinations. Comparison between clinical diagnosis and score diagnosis]. AB - Asthma classification by clinical symptoms and signs (clinical diagnosis) was compared with the classification by score calculated from clinical findings and examinations (score diagnosis) in 25 patients with bronchial asthma. 1. Ten subjects classified as Ia (simple bronchoconstriction type) by clinical diagnosis were divided into 6 cases with expectoration of less than 49 ml a day and 4 cases with expectoration of between 50 and 99 ml. The level of serum IgE and number of eosinophils in BALF were significantly higher in the latter cases than in the former cases. The cases whose expectoration was from 50 to 99 ml a day were classified as Ib (bronchoconstriction with hypersecretion type) by score diagnosis. 2. The six subjects who were classified as type Ib by clinical diagnosis were also evaluated as type Ib by score diagnosis. 3. Nine of the 10 subjects classified as type II by clinical diagnosis were evaluated as type II by score diagnosis. One case, whose score was under 12 points, was evaluated as questionable type II by score diagnosis. PMID- 1622333 TI - [Graduated psychosomatic treatment and quality of life in asthmatics]. AB - We investigated the quality of life (QOL) in 72 patients with bronchial asthma who are under our gradational psychosomatic treatment (GPT) by means of an 11 item questionnaire. The results were summarized as follows: 1) Ninety-two percent of the subjects showed a good understanding of mind-body relations and modified their stressful adaptive patterns. 2) Asthmatic symptoms improved in 86 percent of the subjects. Other symptoms also improved in 72 percent of the subjects. 3) In 81 percent of the subjects, their daily life improved. Furthermore 96 percent of the subjects obtained some advantages through GPT. 4) There were various improvements in psychological states, personal relations and life style in most of the subjects. 5) The attitudes of their families toward the patients improved in 46 percent of the subjects, however 71 percent of the families developed a better understanding of the cause of asthma from the psychosomatic point of view. 6) Most of the subjects with moderate or severe symptoms were considered to have reduced the grade of severity of their symptoms from the doctor's standpoint. PMID- 1622334 TI - [Basic research into the measurement of eosinophil cationic protein (ECP) in blood samples]. AB - Eosinophil cationic protein (ECP), which is one of the eosinophil granule proteins, can now be measured with a radioimmunoassay kit. However, the level of ECP in blood samples is affected by the method of treatment of the samples. We investigated the effect on ECP level of a variety of treatment methods to establish the fundamental condition for the measurement of ECP level in blood samples. ECP levels in serum or heparin plasma increased time-dependently until 2 hr. This increase was considered to be due to active in vitro release of ECP from eosinophils. Serum ECP level at 1 hr was temperature-dependent, being higher at 37 degrees C than at 25 degrees C. On the other hand, ECP level in EDTA plasma did not change significantly during a 3 hr period, and this level of ECP was considered to be that which had been released into the blood in vivo. ECP levels were always in the order of serum greater than heparin plasma greater than EDTA plasma. Though there was a positive correlation between serum ECP level and peripheral blood eosinophil count, the degree of correlation was not strong (r = 0.46, 6, 0.05 greater than p less than 0.01). This suggests that the serum level of ECP, or the "releasibility" of ECP from eosinophils, may reflect the activation of eosinophils. PMID- 1622335 TI - [Induction of IL2 responsiveness in allergen-stimulated lymphocytes from children with post respiratory syncytial virus (RSV) infection]. AB - Induced interleukin 2 (IL2) responsiveness in allergen-stimulated lymphocytes from children with post respiratory syncytial virus (RSV) infection was studied. Induction of IL2 responsiveness in the patients lymphocytes was observed upon stimulation with allergens such as Dermatophgoides farinae (Df) antigen, ovalbumin (OVA) and alpha-casein. Such responses were not induced in age-matched normal lymphocytes. Maximum response was shown in lymphocytes from children who had been suffering from the infection for approximately one month, and the response gradually decreased over the course of eight months. The frequency of induced IL2 responsiveness was unrelated to family history of atopic diseases, although there was a high incidence (67%) of family history among the patients. These results indicate that RSV-sensitized lymphocytes from the patients have acquired hypersensitivity to allergens such as food and mite antigens, factors which are commonly involved in the onset of atopic diseases. PMID- 1622336 TI - Effects of maternal caffeine intake during lactation on molar enamel surfaces in new-born rats. AB - Dams were fed normal laboratory chow until delivery. At birth, the litters were combined, and eight pups were randomly assigned to each dam. Dams with the recombined litters were divided into two groups. Dams of group 1 were fed a 20% protein diet as a control; dams of group 2 were fed a 20% protein diet supplemented with caffeine (2 mg/100 g of the dam's weight). On day 22, the dams of group 2 were anaesthetized with ether. They were injected with 2 iu of oxytocin in order to collect milk. Blood was collected from pups and dams to determine its caffeine concentration. The first and second molars were removed from each pup's mandible and maxilla. Radiographs were taken of 10 randomly selected first or second molars from each group. Four randomly selected molars from each litter were placed in a specially designed chamber and bathed with a constant flow of acid solution to determine the amount of mineral dissolved from the enamel surfaces. The remaining non-acid exposed molars were pulverized in freezer mills. A small portion of this powder was then analysed for the total amount of minerals. No differences were found in the radiographic density of enamel between the groups. The amount of dissolved calcium, phosphorus and magnesium from enamel surfaces in the caffeine group was consistently greater than that of the non-caffeine group in the first molars, whereas, in the second molars, there was no difference between the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1622337 TI - Physical examination of caffeine's effects on the enamel surface of first molar in new-born rats. AB - Samples of the first molars of offspring whose dams were fed a diet supplemented with caffeine were examined by scanning electron microscopy, X-ray diffractometry and electron microprobe analysis. Scanning microscopy of the enamel surface of the caffeine group revealed a consistently rougher surface than in the non caffeine controls, both before and after acid exposure. X-ray diffraction analysis of the pulverized whole tooth in the caffeine group showed broader diffraction peaks for the lattice plane reflections (202) and (300), indicating smaller crystallites. Pure enamel samples of the caffeine group examined with a Gandolfi X-ray camera also revealed more diffuse diffraction lines than in the non-caffeine controls, further indicating smaller crystallites in the enamel. The calcium and phosphorus contents of the acid-exposed samples in both control and caffeine groups were lower than the non-acid exposed control and caffeine groups by electron microprobe analysis. After exposure to acid, the calcium and phosphorus contents of the outer surface of the enamel in the caffeine group were greatly reduced as compared to that of the non-caffeine controls. Thus various methods consistently indicate that caffeine ingestion during early growth affects the enamel surface of the first molars, resulting in impaired mineralization. Caffeine intake may therefore have a negative effect on amelogenesis and possibly increases susceptibility to dental caries. PMID- 1622338 TI - Short-term dentinogenic response of dog dental pulp tissue after its induction by demineralized or native dentine, or predentine. AB - The events initiating the expression of odontoblastic potential by pulpal ectomesenchymal cells were investigated by exposing the pulp to demineralized, native and unmineralized autogenous dentine. The pulp responses to implants were histologically evaluated 3, 7 and 10 days postoperatively, while the surface structure of the newly mineralized matrices was examined 12 and 28 days after implantation. Differentiation of odontoblast-like cells in close proximity to the implanted matrix was consistently demonstrated after exposure to predentine. Scattered columnal cells undergoing polarization, characterized ultrastructurally by the orientation of their rough endoplasmic reticulum, were also found in direct contact with the demineralized dentine. However, in response to demineralized implants, groups of differentiated odontoblast-like cells were clearly seen only in association with a zone of matrix secreted in a polar, predentine-like pattern, indicating an asynchronous inductive influence of this type of implant on pulp cells. Further, the response of pulp cells to native dentine was characterized by the elaboration of a two-layered matrix (a fibrous and a polarly deposited matrix) before initiation of secondary dentinogenesis. Scanning electron microscopy of the newly deposited matrices revealed differences between the indirect matrix synthesis, observed in short-term response to implants of demineralized or native dentine, and the specific, dentinogenic function of the odontoblast-like cells. These observations indicate that the dentine-induced dentinogenesis is initiated by two mechanisms--direct induction of odontoblast-like cells as well as indirect matrix synthesis, which further controls cell polarization. Immobilization of the cells on implanted matrix seems to be the critical requirement for direct expression of the odontoblastic phenotype. PMID- 1622339 TI - Alteration of murine odontogenic patterning and prolongation of expression of epidermal growth factor mRNA by retinol in vitro. AB - Retinoids alter the patterning of murine odontogenesis in vivo and stimulate epithelial proliferation. Because odontogenesis is dependent on proliferation of mandibular epithelium, the effects of retinol on the patterning of odontogenic epithelium were studied. These experiments control for developmental stage, applied retinoid concentration and duration of exposure. Explants exposed for 24 h to 0.1 micrograms/ml of retinol exhibited enhanced odontogenesis. Day-9 mandibles exposed to retinol at 1-5 micrograms/ml had altered epithelial patterns consistent with those in previous in vivo experiments, including supernumerary epithelial buds in regions associated with supernumerary incisors in vivo. These changes were associated with a dose-dependent increase in epithelial proliferation and a prolonged expression of epidermal growth factor (EGF) mRNA. Altered expression of EGF mRNA may be responsible for the disrupted pattern of the dental lamina. This is the first report of a retinoid-induced alteration in EGF mRNA expression. PMID- 1622340 TI - Synergistic effects of dexamethasone on platelet-derived growth factor mitogenesis in vitro. AB - Platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I) interact to stimulate proliferation of fibroblasts in culture. Glucocorticoids variably effect the response of cultured fibroblasts to polypeptide growth factors. This study determined the effects of dexamethasone on growth-factor stimulation of gingival, periodontal ligament and pulp fibroblast proliferation in vitro. Cultures of quiescent, low-passage, human fibroblasts were treated for varying periods of time with transforming growth factor-beta 2 (TGF-beta 2), PDGF and IGF-I: (1) alone, (2) in combination with each other, (3) singly plus dexamethasone, (4) in combination plus dexamethasone. Combinations of human, recombinant PDGF and IGF-I (10-1000 ng/ml) induced significantly higher rates of cell proliferation than either factor alone. Dexamethasone at doses ranging from 10(-5) to 10(-8) M substantially enhanced cell proliferation induced by these combinations and by PDGF without IGF-I but not IGF-I alone. By 6 days after a single application, 2-3 times as many cells were present in the PDGF and dexamethasone cultures as compared to PDGF without IGF-I. TGF-beta 2 specifically blocked the effects of dexamethasone added to PDGF-stimulated cells. Collagen and non-collagenous protein synthesis was not affected by the addition of PDGF and IGF-I with or without dexamethasone. These data suggest that dexamethasone may substitute for IGF-I in PDGF stimulation of cell proliferation. PMID- 1622341 TI - Analysis of major histocompatibility complex (MHC) class I antigen in the rat salivary gland. AB - This antigen was examined in rats of different ages (new-born, 3, 5, 7, 10, 12 and 14 days after birth and adult) by immunofluorescence and immunoelectron microscopy. Changes in each kind of salivary gland when graft versus host disease was induced in recipient rats were also investigated. Monoclonal antibodies (HAM 2 or OX 18) specific to rat MHC class I antigen were used and these were detected by FITC-conjugated anti-mouse immunoglobulin. With HAM 2, MHC class I antigen in the submandibular gland was mostly located in the secretory duct cells; this expression was first found 10 days after birth. The antigen was found on the cell surfaces of the secretory duct cells by immunoelectron microscopy. With OX 18, MHC class I antigen was mainly found in the secretory duct cells, but weak expression was also found in the acinar cells. Localization of the antigen, by HAM 2 and OX 18 was less evident in the secretory duct cells of parotid and sublingual glands. When graft versus host disease was induced, MHC class I antigen (HAM 2) was observed in both acinar and secretory duct cells of the submandibular gland. PMID- 1622342 TI - Bioassay of interleukin 1 (IL-1) in human gingival crevicular fluid during experimental gingivitis. AB - The cytokine IL-1 was demonstrated in crevicular fluid during a 14- and 21-day experimental gingivitis in healthy human volunteers. A sensitive and specific bioassay allowed detection of biologically active IL-1 at levels ranging from 0.18 ng/microliters at baseline to 1.70 ng/microliters in inflamed gingiva. Levels of IL-1 increased rapidly with plaque accumulation and in advance of the subsequent gingival inflammation, peaking within 7 days of the start of gingivitis. As changes in IL-1 were detected before clinically recognizable gingival changes, IL-1 may have potential as an early marker of gingival inflammatory changes. PMID- 1622343 TI - Immunocytochemical localization of growth hormone receptor in rat maxillary teeth. AB - To address the question of what role growth hormone may have in stimulating tooth formation, the distribution of its receptor/binding protein in developing rat incisors and molars was studied immunocytochemically using well-characterized monoclonal antibodies. Ten female 45-day-old Wistar rats were perfused with 4% paraformaldehyde. Five-microns paraffin sections of the growing end of maxillary incisors and molars were cut, deparaffinized and incubated with mouse anti-growth hormone receptor antibodies or control antibodies. A three-layer streptavidin peroxidase technique was used to detect bound antibody. Immunoreaction product was associated primarily with the cytoplasm of cells at certain stages of differentiation. Dividing cells, differentiating preameloblasts and preodontoblasts, secretory ameloblasts and odontoblasts showed immunoreactivity. Undifferentiated dental epithelium cells, stellate reticulum, external dental epithelial cells, mature odontoblasts, and most of cells in the dental papilla were non-reactive. However, at certain stages of tooth development, the stratum intermedium and the external dental epithelium also stained positively. The presence of growth hormone receptor/binding protein in tooth cells at different stages of their development indicates that growth hormone may influence cell proliferation, differentiation and differentiated functions of ameloblasts, odontoblasts and cementoblasts independent of a systemic mediator, and thus may be involved in stimulating odontogenesis directly. PMID- 1622344 TI - Epithelial expression of major histocompatibility complex (MHC) antigens in normal rat salivary and lacrimal glands. AB - The presence and distribution of MHC class I and class II antigens within these glands of Wistar and Lewis rats was studied using monoclonal antibodies and an indirect immunoperoxidase technique. In rats of both strains and sexes, MHC class 1 antigens were expressed by ductal epithelium in addition to vascular endothelium and other connective tissue elements. Except for a small proportion of secretory cells within lacrimal glands, acini were uniformly negative for class I antigen. MHC class II immune response-associated (Ia) antigens were expressed by stromal dendritic cells in all glands. Glandular expression of Ia was limited to submandibular glands of the two strains. In Lewis rats, staining was detected in some striated and collecting ducts, whereas positive glandular reactivity in Wistar rats was predominantly within the granular-cell tubules. Quantitative histomorphometric studies of Wistar submandibular glands, taken from 2.5-60-week-old male and female animals, demonstrated a close relationship between the extent of glandular Ia reactivity and postnatal granular-cell tubule development. These results indicate that whilst constitutive expression of Ia is a feature of rat submandibular epithelium, the glandular components involved are strain dependent. PMID- 1622345 TI - Latex agglutination test for detection of mutans streptococci in relation to dental caries in children. AB - A simple and rapid system based on a latex agglutination (LA) reaction was devised for the detection of mutans streptococci in dental plaque. Latex particles were sensitized with antibodies against whole cells of Streptococcus mutans strains MT8148 (serotype c), MT703R (e) and OMZ175 (f) and Strep. sobrinus strains B13 (d) and 6715 (g). These sensitized particles were agglutinated within a few minutes after addition of 1.0-10 ng serotype-specific antigen from the homologous organisms or the nitrous acid extract of whole cells at 10(5)-10(6) c.f.u. The LA test specifically differentiated not only mutans streptococci from the other oral streptococci but also Strep. sobrinus from Strep. mutans. The LA test was also applicable to extracts of plaque from 206 human subjects who harboured mutans streptococci. In clinical trials, the outcome of the LA test correlated significantly with the number of mutans streptococci found in plaque (p less than 0.0001), which was quantified by the selective cultivation of mutans streptococci. Furthermore, the LA test discriminated between Strep. mutans and Strep. sobrinus from human dental plaque. The sensitivity and the specificity of the LA test for detection of mutans streptococci were 78.9 and 100%. The degree of reactivity in the LA test correlated significantly with the number of decayed tooth surfaces (p less than 0.0001) and decayed and filled tooth surfaces (p less than 0.0001). These results suggest that the LA test could be useful clinically for the detection of mutans streptococci in dental plaque as well as serving as a caries-activity test. PMID- 1622346 TI - The effect of an educational intervention on the use of peri-operative antimicrobial agents. AB - The objective of this study was to evaluate the effect of an educational intervention on the prescribing behaviour of doctors who order antimicrobial therapy for patients undergoing abdominal surgery. Two confidential criterion audits were separated by the intervention which involved completion of a 10-item questionnaire followed by a fully referenced answer sheet. The results showed a significant improvement in the prescribing habits of the junior surgical staff after the educational intervention. The overall error rate decreased from 50% to 20% (P = 0.003). PMID- 1622347 TI - Child-care needs of patients at the Royal Women's Hospital, Brisbane. AB - Eight hundred and ninety-eight patients of the Royal Women's Hospital, Brisbane were surveyed by phone and questionnaire to identify their hospital related child care needs. In addition, staff in acute admitting areas of the hospital were asked to provide details of child-care problems. Twenty-five (5.2%) of the sample reported hospital related child-care problems, 166 (39.7%) respondents stated that they would use a hospital child-care service on a casual basis and 45 (10.8%) that they would use one for the duration of their stay. PMID- 1622348 TI - The application of continuous quality improvement tools in reducing the length of stay for hip replacement patients: a base hospital's experience. AB - The quality assurance (QA) initiative has been slow to show results. Quality assurance tools have been underdeveloped, and quality by inspection unacceptable to clinicians. A base hospital's experience with continuous quality improvement (CQI) as a means to more effective quality assurance is described. Discharge data grouped into diagnosis related groups (DRG) and analysed for inter-hospital comparison provided reliable statistical data with which to monitor the hospital's performance. The CQI tools were used to analyse the nature of the problem, and correct the deficiency. The new methodology would seem to indicate greater promise for successful quality assurance programmes in the future. PMID- 1622350 TI - Administering non-restricted medications in hospital: the implications and cost of using two nurses. AB - In an effort to improve patient safety, some hospitals require that two nurses rather than one administer all medications. Such a policy has not been subjected to an economic evaluation. The authors conducted a cross-over study comparing error rates when medication was administered by two nurses as against a single nurse. During a 46 week study period, 319 errors were detected among 129,234 medications administered in a geriatric assessment and rehabilitation unit, giving an overall error rate of 2.5 per 1000 medications. The vast majority of errors detected were relatively minor and had no serious adverse consequences. The error rate per 1000 medications administered by a single nurse was 2.98 (95% CI: 2.45-3.51) and was statistically significantly higher than 2.12 (95% CI: 1.69 2.55) per 1000 for two nurses. A time and motion study indicated that when two nurses rather than one administered medication an additional 17.1 h of nursing time was required per 1000 medications administered. The authors conclude that the use of two nurses to administer medication does statistically significantly reduce the medication error rate, but the clinical advantages are dubious and in our view such a policy cannot be recommended. PMID- 1622349 TI - Colonoscopy in a private hospital: continuous quality improvement in practice. AB - This paper documents serial audits on technical aspects of the performance of fibre-optic examination of the large intestine by a number of proceduralists, in one institution, over 7 years. The completeness of the procedure and the associated morbidity are recorded and compared with results reported in the world literature. The study provides a clear demonstration of continuous quality improvement in practice. PMID- 1622351 TI - Concurrent case note screening: failure to demonstrate benefit. AB - In 1991 the third of a series of trials of concurrent case note screening was conducted over a 4 month period in one surgical and one medical unit of a busy metropolitan public teaching hospital in South Australia. The conclusion reached was that there is insufficient evidence of consistent improvement to justify the continuation of this expensive method of quality assurance. Traditional monitoring of performance by consultants, perhaps with the aid of computer assisted management information, should achieve similar results. PMID- 1622352 TI - The paediatric hospital medical record: a quality assessment. AB - The objective of this study was to assess the quality of the medical contribution to patient records in a children's department. It was carried out in a tertiary level teaching hospital. A structured audit of 100 randomly selected case records, with independent observers using a grading system for 3 of the measures, was performed. The outcome provides a comparison with the hospital's guidelines for case histories and notes. The results of this study show inadequate documentation of basic information. Communication was hindered by poor hand writing and the use of abbreviations. Overall comprehension of the course of the patients' illnesses was regarded as only fair to average. Recording of diagnosis and initial plans of management were present in over 70% of records. While discharge information was well recorded, the recommendation for the duration of drug therapy was inadequate. Mediocre handwriting and poor documentation are still prevalent in medical records. Strict supervision of this important area of medical practice is mandatory. PMID- 1622354 TI - Serial killers and sexual violence. The whys and wherefores. PMID- 1622355 TI - Are you seeing a mass killer? AB - Whatever the underlying reasons, we have to be prepared for more episodes of this nature, and as medical practitioners do what we can to prevent them. With the wisdom of hindsight it is possible to suggest that the Knight and Vitkovic killings could have been avoided. Knight had a history of violence causing him to leave Duntroon Military College. Despite this, he was not prevented from holding a shooter's licence in his own State, and in particular nothing was done to stop him having a collection of weapons. Vitkovic sought help from a university psychology clinic and from the Church of Scientology. Coroner Hal Hallenstein criticised the Church of Scientology for failing to help Vitkovic after he failed their personality test on 8 October 1987, and also suggested that a general obligation be placed on psychologists to refer to a psychiatrist if they think that is required. Practitioners' concern for their own safety must be considered. It would have been an extraordinarily difficult and possibly risky task to try to deter Julian Knight from persisting in his adoration of aggression and love of weapons, or to talk Frank Vitkovic out of watching violent films and videos and later purchasing a semi-automatic weapon. Nevertheless, the practitioner's responsibility remains, and as a last resort notification to police of the risk posed by the person might have to be considered. Unfortunately the anonymity of a practitioner making such a notification might not be able to be guaranteed, given current freedom of information legislation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1622353 TI - Adult discharge planning and nursing home placement: a study of risk factors for quality assurance. PMID- 1622356 TI - The prediction of violence. AB - Violence is prevalent in Australian society. Victims often present to general medical practitioners for care of the physical, psychological and social consequences. It is, therefore, important to be able to identify potential offenders in order to anticipate aggression and prevent it, if possible. A motivational cycle for violence is proposed, some common predictors examined and the problem of reliable prediction discussed. PMID- 1622357 TI - On understanding homicide. AB - There are many faces of homicide, and there are no simple preventive cures. There is scarce comfort in knowing the homicide is, in fact, rare (there being roughly 60 cases per year in Victoria), or that a person is several times more likely to die by his or her own hand than that of someone else. Our current research suggests that there are some consistent patterns in the form that homicide takes. Hopefully, the more we understand these scenarios, the better we will be able to recognise the underlying conditions that push people to the point where they will think the unthinkable, and knowingly take the life of another person. PMID- 1622358 TI - 'No longer nineteen'. A review of Vietnam veterans in everyday practice. AB - After working with a number of Vietnam veterans I was confronted with my ignorance of the war and its aftermath. I hope this article helps others wishing to improve their understanding of these patients. PMID- 1622359 TI - Management of the traumatised patient. AB - I have tried to present a range of suggestions for the therapeutic management of traumatised victims and have used illustrations based on my work with victims of armed robbery. In general, however, I believe that the principles outlined are applicable to a wide range of trauma and I have found these ideas valuable in dealing with victims of crime in general, in counselling staff involved in industrial accidents and in providing support to those involved in natural or man made disasters. The key principles include: a prompt and timely intervention; the use of properly trained professional staff to provide a structured debriefing programme that focuses on the opportunity to discuss feelings; providing information and education about normal responses to trauma and helping to normalise the individual's response to the situation. Re-establishing a normal lifestyle as soon as possible has been shown to be critical to speedy recovery; as has professional support, continuing follow up and reassurance that most victims recover without going on to develop a post traumatic stress disorder. An integrated team approach to the management of traumatised victims is critical and there must be communication between the general practitioner, any counsellors involved in providing services to the traumatised person and, of course, the victim. The general practitioner is often the primary link in the management chain and the positive relationship that many people have with their general practitioner can be used to great effect in helping to manage a recovery from crisis. PMID- 1622360 TI - Carbamazepine and sciatica. AB - Carbamazepine is useful in the management of various painful conditions. The mechanism of its action is not known. Whatever its mechanism, Carbamazepine appears to have a good chance of relieving painful disorders with episodic, flashing pain. Two cases of sciatica responding favourably to carbamazepine are presented in detail. PMID- 1622362 TI - The first 100 independent quality assurance options. AB - The independent option route to quality assurance is attracting projects from general practitioners interested in a wide variety of clinical, educational and community roles. Despite the worthwhile increase in confidence and satisfaction claimed by participants, few projects attempt to measure objectively the impact on patient care. Following an analysis of the first 100 completed independent option projects, the Quality Assurance Unit is in a position to offer better guidelines to help future participants gain maximum benefit from their projects. PMID- 1622361 TI - Communication problems of the chronically ill. AB - Patients with severe pain have a reduced capacity to communicate with doctors. These patients have depleted resources. Doctors are pressed for time. Patients not responding to treatment present doctors with communication tasks. Doctors need to persist gently in telling the 'unacceptable' bad news until it is reluctantly accepted. PMID- 1622363 TI - Injection for Achilles tendinitis. PMID- 1622365 TI - Great expectations. PMID- 1622364 TI - Neil Edwin Carson. Academic general practitioner, leader and achiever. AB - Professor Neil Carson, who is to retire as Chairman of Monash University's Department of Community Medicine at the end of this year, has completed a significant and successful term marked by many achievements. His energy, vision and ability to acquire and channel resources have helped develop a vibrant and productive department. His wise counsel and negotiating skills have led to important achievements for the cause of general practice in both the political sphere and in academic institutions. He was the founder and first president of the Australian Association for Academic General Practice. His impact on medical education, especially for general practice in Australia, has been far reaching. PMID- 1622366 TI - Attitudes of Victorian rural GPs to country practice and training. AB - This article reports findings from a study undertaken in early 1991 about attitudes of rural general practitioners in Victoria to country practice and training. A questionnaire was sent to all rural general practitioners and two random samples of metropolitan GPs: one group in suburban practice and another group in fringe metropolitan areas. A 75% response rate was achieved providing information representative of most general practitioners in Victoria. Study findings cover aspects of rural GPs' personal background including training; practice description including continuing education; reasons for choosing country practice; reasons for staying in country practice; reasons for leaving country practice; and suggestions for improving recruitment, training and retention of rural GPs. PMID- 1622368 TI - Patient education. Hiatus hernia. PMID- 1622367 TI - Basic management of myocardial infarction. PMID- 1622369 TI - Excision of lipomas. PMID- 1622370 TI - Awakenings from within and without. PMID- 1622371 TI - Atrio-ventricular (A-V) block. PMID- 1622372 TI - The mouth ulcer that would not heal. PMID- 1622374 TI - Hip and buttock pain in adults. AB - Hip and buttock pains in adults require careful evaluation to determine exactly what anatomical structure the patient is referring to when presenting with 'pain in the hip'. Pain in the posterior hip region and buttocks usually originates from dysfunction of the lumbosacral spine. Osteoarthritis of the hip is an important disorder that can refer pain to the anteromedial aspect of the knee. PMID- 1622373 TI - Slowing up--it's just old age ... or is it? PMID- 1622375 TI - Sampling bias in asthma surveys of patients attending general practitioners in south-western Sydney. AB - Results from asthma surveys in patients attending general practitioners were compared with data from population-based samples. The prevalence of asthma symptoms and optimal asthma management were more common in the GP attenders. Attention should be paid to potential sources of sampling bias in chronic disease prevalence research in primary care settings. PMID- 1622376 TI - Breastfed infants. PMID- 1622377 TI - [Latent Chlamydia infections as the cause of health disorders in swine, cattle and sheep breeders in Czechoslovakia]. AB - For a twelve year period the health condition of a large group of pig-, cattle- and sheep-breeder was controlled and at the same time an inquiry was carried out why these people suffer from high occurrence of specific health problems which among the rest of the population appear in smaller extent. The performed investigation shows that the primary cause of the specific problems is a latent infection caused by the chlamydia microorganism, namely by the Chlamydia trachomatis group, that can be transferred from animals on people. These microorganisms survive permanently and parasite in the living cells of animals and people and they cause a wide range of specific health difficulties, often subjective, painful and very unpleasant ones, without any manifestation of clinical symptoms which could suggest an infectious disease. These properties of the agent and the fact, that neither human nor veterinary medicine inquire the problems of the relationship between the latent infection and the health of people, makes Chlamydia an extremely dangerous factor affecting people's health. Our paper includes anamnestic data of specific health problems of 746 breeders from 31 farms and results of serological examinations of a group of people with antigens Chlamydia psittaci and Chlamydia trachomatis. The paper also includes a biological experiment which the rise of antibodies of a guinea pig kept and fed with table scraps in the family of one the afflicted breeders as well as the results of serological examinations of a group of animals, the most frequent health problems at the latent course of disease, the course of the disease itself and the author's opinions on necessity of further investigation of the human medicine problems. PMID- 1622378 TI - [The effect of a restriction of nutrient intake on the composition of the blood and on the development and composition of different tissues of sheep during growth. 1. The level of the hematocrit and hemoglobin in the blood, that of protein, alpha amino-N, remaining N, glucose, FFA, insulin, beta-hydroxybutyrate, Na, K, Ca, Mg, Pa, Fe, iron-binding capacity, Cu and Zn and the activities of ALT, AST, LDH, GGT and AP in plasma at slaughter]. AB - In lambs after weaning with a body weight of 16.3 +/- 1.5 kg (group 1) and in sheep after a period of fattening with an increase of the body weight of 72.2 +/- 13.6 (group 2), of 184.4 +/- 12.2 (group 3) respectively of 302.1 +/- 24.3 g per day (group 4) the concentration of the components mentioned in the title was analysed in blood and plasma. The hematocrit, the concentration of Hb in the blood and that of total protein, of nonprotein-N, of Na, of Ca, of the iron binding capacity and of Zn as well as the activity of the 5 enzymes in the plasma of the sheep of group 4 were higher than that of the group 2. Stress by the transport and stunning increased the concentration of free fatty acids in the plasma. The significance of the results for the clinical-chemical diagnosis is discussed. PMID- 1622379 TI - [The significance of small mammals in the epizootiology of leptospirosis in livestock]. AB - 1. Favourite species of rodents in sheds and their surroundings are rats (Rattus norvegicus, R. rattus) and house mouse (Mus musculus). From the epizootiological point of view only R. norvegicus is important as the maintenance host of L. copenhageni. 2. In surrounding of sheds vole (Microtus arvalis) and back-striped field mouse (Apodemus agrarius) are sources of infection for livestock. 3. Transmission of leptospira occurs via infected environment. The tenacity of Leptospira mozdok and L. grippotyphosa under field conditions suffices to maintain the chain of infections. PMID- 1622380 TI - [Bacterial studies on the occurrence of Mycobacterium paratuberculosis in fecal samples of zoo ruminants]. AB - Mycobacterium (M.) paratuberculosis was isolated from fecal samples of 3 (21.4%) from 14 mouflons, of 10 (20.4%) from 49 dwarf goats, of 5 (14.3%) from 35 Cameroon sheep and of 1 (9.1%) from 11 alpine ibex. M. paratuberculosis could not found by cultural method in fecal samples of 22 Pinzgauer goats, of 15 bantengs, of 9 wild goats, of 9 skuddens, of 6 four-horned sheep, of 3 red-head sheep, and of 1 chamois. From all 19 animals with cultural positive fecal samples complement binding antibodies against M. paratuberculosis could not be found in the corresponding serum samples. The results confirm that M. paratuberculosis is more frequently in small zoo ruminants than up to now was suspected. The cultural examination of fecal samples has been proved to be a better method for detecting animal excretors than serological investigations by means of the complement fixation test. PMID- 1622381 TI - [Scanning electron microscopic studies of the odontoblasts and the pulpodentinal border in domestic sheep (O. ammon aries Linnaeus, 1758)]. AB - In order to investigate odontoblasts and predentin surfaces using SEM techniques, teeth of sheep with one or several roots were subjected to critical point drying. The odontoblasts of the root pulp are distinguished in their shape and arrangement pattern from those in the crown pulp. They regularly are detaching only one process of Tomes, which is extending up to the border between dentin and enamel and which shows a dendritic ramification in the dentin next to the enamel. The distal cell portions of the odontoblasts are joined together by a system of terminal bars. The collagen structures observed between the odontoblasts and predentin are considered to be von Korff's fibres as found in man. PMID- 1622382 TI - [Friedrich Ludwig Urban--from blacksmith to veterinarian. The history of his life]. AB - Friedrich Ludwig Urban lived from 1808 to 1879. There is documentary evidence that he worked as a veterinary surgeon in Berlin and fought here on the barricades in 1848. Little is known about either his professional career or his private life. The author uses hitherto unpublished facts to present a detailed picture of the professional work and private life of Friedrich L. Urban, making a contribution to the historiography of veterinary surgery. PMID- 1622383 TI - Targeting proteins to mitochondria: a current overview. PMID- 1622384 TI - Stimulation of NADH oxidase activity from rat liver plasma membranes by growth factors and hormones is decreased or absent with hepatoma plasma membranes. AB - Plasma membranes of rat liver isolated by aqueous two-phase partition exhibited basal levels of NADH oxidase activity that were increased approx. 2-fold by addition of hormones and growth factors to which liver cells were known to respond. In contrast, hepatoma plasma membranes demonstrated an intrinsically increased level of NADH oxidase, which was not stimulated further by addition of growth factors. The results suggest that the NADH oxidase of the hepatoma plasma membrane is no longer correctly coupled to hormone and growth-factor receptors. This biochemical defect may parallel the loss of growth control that is characteristic of neoplastic transformation in hepatocarcinogenesis and other transformation systems. PMID- 1622385 TI - Leukoregulin down-regulates type I collagen mRNA levels and promoter activity in human dermal fibroblasts, and counteracts the up-regulation elicited by transforming growth factor-beta. AB - Leukoregulin (LR), a T-cell-derived growth factor, modulates fibroblast functions in vitro [Mauviel, Redini, Hartmann, Loyau & Pujol (1991) J. Cell Biol. 113, 1455 1462]. In the present study, incubation of human dermal fibroblasts with LR (0.1 2 units/ml) resulted in decreases in the mRNA steady-state levels for alpha 1(I), alpha 2(I) and alpha 1(III), but not alpha 2(V), collagen genes. LR also down regulated alpha 2(I) collagen promoter activity in transient cell transfections of control cells as well as those incubated with transforming growth factor-beta, a potent up-regulator of collagen type I gene expression. Thus LR is a strong inhibitor of type I collagen gene expression, acting at the level of transcription. PMID- 1622386 TI - Identification of cytosolic protein tyrosine kinases of human prostate by renaturation after SDS/PAGE. AB - The identification of protein tyrosine kinases (PTKs) was successfully achieved by renaturation in gels after SDS/PAGE. To this effect, samples were mixed with a PTK substrate, namely the polydispersed co-polymer of glutamic acid and tyrosine [poly(Glu, Tyr), M(r) from 30,000 to 94,000], and were simultaneously submitted to electrophoresis. Following guanidine hydrochloride denaturation, renaturation and phosphorylation with [gamma-32P]ATP, kinase activity was detected by autoradiography. When applied to cytosol from human hyperplastic prostate, eleven protein kinases were detected, among which one major (M(r) 50,000) and two minor proteins (M(r) 40,000 and 38,000) were identified as PTKs by the presence of phosphotyrosine. Incubation of the gel in hot alkali after glutaraldehyde cross linking almost completely eliminated the detection of non-PTK enzymes. On the other hand, in the absence of poly(Glu,Tyr), no PTK activity was detected. Partial purification of cytosolic PTKs indicates that the native M(r) of the major phosphotransferase was 44,000, as estimated by gel filtration following ammonium sulphate precipitation and anion-exchange chromatography. Upon renaturation after electrophoresis, this fraction showed only one major band active on poly(Glu,Tyr) which was associated with the polypeptide of M(r) 50,000. This enzyme was also identified following two-dimensional electrophoresis and renaturation in the presence of poly(Glu,Tyr), allowing the determination of a pI in the range 7.5-7.8. Thus PTKs can be easily renatured following electrophoresis and rapidly identified on the basis of their M(r) and pI in both crude or partially purified preparations. With the crucial role played by PTKs in the activation of cell function and carcinogenesis, this procedure could be useful in the identification of such enzymes and in distinguishing them from their substrates in gels. PMID- 1622387 TI - Effect of permethylation on the haemolytic activity of melittin. AB - The cytolytic activity of the bee venom toxin, melittin, is abolished on permethylation of the ammonium groups into quaternary trimethylammonium groups. The loss of activity in permethylated melittin may result partly from the absence of the hydrogen bonding potential and partly from steric effects involving the bulky trimethylammonium groups. Displacing the trimethylammonium groups away from the backbone to relieve steric effects (by acylating melittin with glycine or 5 aminopentanoic acid followed by permethylation) restored moderate activity at 5 fold increase in concentration. PMID- 1622388 TI - Polyclonal antibody-catalysed amide hydrolysis. AB - 1. The activated amide (4-nitroanilide), N-(4-nitrophenyl) N'-butyl-1,4 phenylenediacetamide (III) was synthesized. 2. A polyclonal antibody preparation (PCA 270-29) was elicited in a multigeneration cross-bred sheep (no. 270) and isolated 29 weeks into the immunization schedule by procedures described previously for PCA 270-22 [Gallacher, Jackson, Searcey, Badman, Goel, Topham, Mellor & Brocklehurst (1991) Biochem J. 271, 871-881]. These involved the use of an amide conjugate bonded through the carboxy group of 4-nitrophenyl 4' carboxymethylphenyl phosphate and an amino group of keyhole-limpet haemocyanin as the immunogen. 3. PCA 270-29 was shown to catalyse the hydrolysis of both the carbonate ester substrate 4-nitrophenyl 4'-(3-aza-2-oxoheptyl)phenyl carbonate (I) and the amide substrate (III). Both catalyses obeyed the Michaelis-Menten equation with the following values of the parameters at 25 degrees C: for the hydrolysis of (I) at pH 8.0, Km = 3.96 +/- 0.28 microM and k(cat.) = 0.135 +/- 0.004 s-1 (k(non-cat.) = 1.99 x 10(-4) s-1); for the hydrolysis of (III) at pH 9.0, Km = 5.4 +/- 1.4 microM and k(cat.) = (5.95 +/- 0.75) x 10(-5) s-1 (k(non cat.) = approx. 2 x 10(-7) s-1). 4. The finding that PCA 270-29 is almost equally effective as a catalyst for the hydrolysis of the amide (III) as for that of the carbonate ester (I) when allowance is made for the different intrinsic reactivities of the two types of substrate is discussed. The catalytic characteristics of PCA 270-29, the first example of a polyclonal catalytic antibody preparation shown to catalyse the hydrolysis of an amide and the first example of an antibody preparation (monoclonal or polyclonal) with such catalytic character to be produced by use of a phosphate immunogen, are compared with those of the small number of other antibody-mediated hydrolyses of amides in the literature. PMID- 1622389 TI - Identification of a protein transiently phosphorylated by activators of endothelial cell function as the heat-shock protein HSP27. A possible role for protein kinase C. AB - Several agonists of endothelial cell function (thrombin, histamine, dioctanoylglycerol, phorbol 12-myristate 13-acetate, interleukin-1) have previously been shown to enhance the level of phosphorylation of an undefined 29,000-M(r) protein (P29). Comparison of this protein with other phosphoproteins suggested that it may be related to the mammalian heat-shock protein HSP27. Immunoprecipitation and immunoblot analysis with antibodies specific for human HSP27 demonstrated that P29 was immunochemically identical with HSP27. Further characterization of agonist-induced phosphorylation of HSP27 indicated that phosphorylation occurred exclusively on serine residues, and phosphopeptide analysis of tryptic- and chymotryptic-cleavage products demonstrated that the phosphopeptides generated were identical for each agonist and okadaic acid. Down regulation of protein kinase C-alpha by prolonged treatment with phorbol esters eliminated the ability of phorbol 12-myristate 13-acetate, dioctanoylglycerol, thrombin and histamine to phosphorylate HSP27 above background levels and deceased interleukin-1-stimulated HSP27 phosphorylation by 60%. These data suggest that the various agonists employed stimulate HSP27 phosphorylation through similar mechanisms and that protein kinase C is probably involved. PMID- 1622390 TI - Mammary development and milk secretion in transgenic mice expressing the sheep beta-lactoglobulin gene. AB - Mammary development and milk secretion were studied in transgenic mice which exhibited mammary tissue-specific expression of the sheep beta-lactoglobulin gene, and secreted significant quantities of the foreign protein in milk. Mammary development was unaffected by transgenesis. Tissue DNA content and the activities of several key enzyme markers of cell differentiation were similar in transgenic mice and non-transgenic controls. Milk yield, whether estimated by pup weight gain or measured by a 3H2O-dilution method, was unchanged by foreign gene expression. Gross milk composition, including milk protein concentration, was also similar in transgenic and non-transgenic animals, even though beta lactoglobulin accounted for 29% of total milk protein. Therefore the foreign gene product was synthesized at the expense of endogenous milk proteins. However, transgenic mammary tissue in vitro exhibited a significantly higher rate of total protein synthesis than did control tissue. This suggested that a factor limiting milk protein synthesis or secretion in transgenic mice in vivo may have been removed by short-term explant culture of mammary tissue. The results emphasize that the use of transgenesis for manipulating milk composition may depend not only on high-level mammary-specific expression of the foreign gene, but also on the biosynthetic capacity of the mammary gland itself. PMID- 1622391 TI - Variations in hepatic carbon flux during unrestricted feeding. AB - Previous findings have established a pivotal role for hepatic pyruvate dehydrogenase complex (PDH) in regulating hepatic carbon flux during the starved to-fed and fed-to-starved nutritional transitions [Holness, McLennan, Palmer & Sugden (1988) Biochem. J. 252, 325-330; Holness & Sugden (1990) Biochem. J. 268, 77-81]. We have therefore examined liver PDH activities during the light and dark phases of the feeding cycle in the adult rat in relation to hepatic glycogenesis, fatty acid synthesis and cholesterogenesis. There was significant synchronous suppression of lipogenesis and glycogenesis during the light phase; rates were restored asynchronously during the dark (feeding) phase. Glycogen concentrations declined during the light phase and increased during the dark phase. Despite quite dramatic changes in rates of glycogen and lipid synthesis and hepatic glycogen concentrations during the light and dark phases, hepatic PDHa (active form) activity remained relatively unchanged. Qualitative and quantitative differences in the pattern of change in rates of synthesis of fatty acid and cholesterol suggested regulation at pathway-specific sites distal to PDH. PMID- 1622392 TI - Novel linear and branched polyamines in the extremely thermophilic eubacteria Thermoleophilum, Bacillus and Hydrogenobacter. AB - Novel tertiary branched tetra-amines, quaternary branched penta-amines, linear penta-amines and linear hexa-amines were distributed as the major polyamines in six obligately extremely thermophilic eubacteria belonging to Thermoleophilum, Bacillus or Hydrogenobacter. The major polyamine of Thermoleophilum album and Thermoleophilum minutum was identified as a quaternary branched penta-amine, 4,4 bis(3-aminopropyl)-1,8-diamino-4-azaoctane (NH2[CH2]3N+([CH2]3NH2)2[CH2]4NH2) by h.p.l.c., t.l.c. and g.c.-m.s. Hydrogenobacter thermophilus and Hydrogenobacter halophilus contained another quaternary branched penta-amine, 4,4-bis(3 aminopropyl)-1,7-diamino-4-azaheptane (NH2[CH2]3N([CH2]3NH2)2[CH2]3NH2) as the major polyamine, and tertiary branched tetra-amines (4-(3-aminopropyl)-1,7 diamino-4-azaheptane (NH2[CH2]3N([CH2]3NH2)[CH2]3NH2), 4-(3-aminopropyl)-1,8 diamino-4-azaoctane (NH2[CH2]3N([CH2]3NH2)[CH2]4NH2)) and 4,4-bis(3-aminopropyl) 1,8-diamino-4-azaoctane were confirmed as minor components. Bacillus schlegelii contained a branched tetra-amine, 4-(3-aminopropyl)-1,8-diamino-4-azaoctane, a branched penta-amine, 4,4-bis(3-aminopropyl)-1,8-diamino-4-azaoctane, a linear penta-amine, 1,16-diamino-4,8,13-triazahexadecane (NH2[CH2]3NH[CH2]3NH[CH2]4NH[CH2]3NH2) and linear hexa-amine(s), 1,20-diamino 4,8,12,17-tetra-azaeicosane (NH2[CH2]3NH[CH2]3NH[CH2]3NH[CH2]4NH[CH2]3NH2 ) and/or 1,20-diamino-4,8,13,17-tetra-azaeicosane (NH2[CH2]3NH[CH2]3NH[CH2]4NH[CH2]3NH[CH2]3NH2 ). PMID- 1622393 TI - Activation of calpain I in thrombin-stimulated platelets is regulated by the initial elevation of the cytosolic Ca2+ concentration. AB - The source and concentration of Ca2+ required to activate calpain I were investigated in thrombin-stimulated platelets. The concentration of cytosolic free Ca2+ ([Ca2+]i) was measured in platelets containing fura-2-AM, and exhibited a biphasic response after stimulation with 0.05, 0.1 or 0.5 NIH units of thrombin/ml. An initial transient elevation, which was predominantly dependent upon Ca2+ released from the internal stores into the cytosol, peaked at 15 s after stimulation, and a secondary sustained elevation, which was due to Ca2+ influx, was observed following the initial elevation. Calpain I was present at about 540 ng/10(8) unstimulated platelets, as measured by immunoblotting using rabbit anti-(human calpain I) IgG. Calpain I was activated 10 s after thrombin stimulation, as determined by the appearance of the 78 kDa and 76 kDa forms on immunoblots. The activation ratio of calpain I was calculated as the amount of the 78 + 76 kDa forms as a percentage of the total (80 + 78 + 76 kDa), and was influenced by the extent of the initial transient [Ca2+]i elevation after stimulation. An initial increase in [Ca2+]i of 300 nM was required to achieve the maximal activation (60%) of calpain I, and half-maximal activation occurred at 160 nM- Ca2+]i. These results suggest that the activation of calpain I in platelets is regulated by the initial elevation in Ca2+]i after thrombin stimulation, and does not necessarily require a Ca2+ influx. PMID- 1622394 TI - A novel mechanism for isoprenaline-stimulated proliferation of rat parotid acinar cells involving the epidermal growth factor receptor and cell surface galactosyltransferase. AB - Chronic injections of epidermal growth factor (EGF) or the beta-adrenergic receptor agonist isoprenaline resulted in rat parotid gland hypertrophy and hyperplasia. Introduction of a polyclonal antibody to EGF or the EGF-receptor (EGF-R) caused a specific retardation of acinar cell proliferation when injected along with the growth factor. Meanwhile, only the antibody to EGF-R caused a dose dependent retardation of proliferation on co-administration with isoprenaline both in vivo and in vitro. The antibody injected alone had no effect on cell growth. When cells were incubated in the presence of EGF, plasma membranes from isoprenaline-treated and control animals showed phosphorylation of the EGF-R tyrosine moieties and transient increases in membrane-associated phospholipase C gamma. Isoprenaline did not stimulate phosphorylation of the EGF-R in isolated plasma membranes. However, activation of the phosphotyrosine-signalling pathway could be duplicated by incubating isoprenaline-treated acinar cells, but not control cells, with bovine galactosyltransferase. Immunopurified EGF-R demonstrated variations in reactivity with two different lectins after treatment of the cells with the beta-agonist as well as increased galactosyltransferase substrate capacity in vitro. In addition, incubation of intact acinar cells and isolated plasma-membrane fractions from isoprenaline-treated rats with UDP [14C]galactose resulted in an increased incorporation of label into the EGF-R. The results suggest that the carbohydrate moiety of the EGF-R has been altered in isoprenaline-treated animals allowing galactosyltransferase now to recognize this receptor. This interaction may in part mediate proliferation of parotid acinar cells. Indeed, we have previously shown that an antibody to galactosyltransferase is capable of blocking isoprenaline-mediated acinar cell proliferation in vivo [Humphreys-Beher, Schneyer, Kidd & Marchase (1987) J. Biol. Chem. 262, 11706 11713]. PMID- 1622395 TI - Mechanism linking glycogen concentration and glycogenolytic rate in perfused contracting rat skeletal muscle. AB - The influence of differences in glycogen concentration on glycogen breakdown and on phosphorylase activity was investigated in perfused contracting rat skeletal muscle. The rats were preconditioned by a combination of swimming exercise and diet (carbohydrate-free or carbohydrate-rich) in order to obtain four sub-groups of rats with varying resting muscle glycogen concentrations (range 10-60 mumol/g wet wt.). Pre-contraction muscle glycogen concentration was closely positively correlated with glycogen breakdown over 15 min of intermittent short tetanic contractions (r = 0.75; P less than 0.001; n = 56) at the same tension development and oxygen uptake. Additional studies in supercompensated and glycogen-depleted hindquarters during electrical stimulation for 20 s or 2 min revealed that the difference in glycogenolytic rate was found at the beginning rather than at the end of the contraction period. Phosphorylase alpha activity was approximately twice as high (P less than 0.001) in supercompensated muscles as in glycogen-depleted muscles after 20 s as well as after 2 min of contractions. It is concluded that glycogen concentration is an important determinant of phosphorylase activity in contracting skeletal muscle, and probably via this mechanism a regulator of glycogenolytic rate during muscle contraction. PMID- 1622396 TI - Effects of calmodulin antagonists on antibody binding to calmodulin. Distinct conformers of calmodulin induced by the binding of drugs. AB - An indirect enzyme-linked immunosorbent assay has been used to study the interactions between calmodulin and two calmodulin antagonists, trifluoperazine and a neuropeptide isolated from the hypothalamus. The binding of a monospecific anti-calmodulin antibody, raised in rabbit against dinitrophenylated calmodulin, to calmodulin was tested at various concentrations of these drugs under equilibrium conditions. Trifluoperazine at low concentrations stimulated, but at relatively high concentrations inhibited, immunocomplex formation. The neuropeptide displaced the antibody from calmodulin at nanomolar concentrations. Enzyme-linked immunosorbent assays were also carried out with the large tryptic fragments of calmodulin. The results suggest that (i) the C-terminal fragment binds the antibody with an affinity which is comparable with that of intact calmodulin; (ii) the neuropeptide can form complexes with both N- and C-terminal fragments, but with two orders of magnitude less activity in case of the C terminal fragment; and (iii) trifluorperazine does not stimulate antibody binding to the C-terminal fragment. Therefore the tertiary structure of calmodulin must be intact to ensure long-distance interactions between the binding sites of trifluoperazine, the neuropeptide and the antibody. These interactions may produce distinct conformers of calmodulin which may exhibit altered potency, not only for antibody binding but also for stimulation/inhibition of target enzymes. PMID- 1622397 TI - Purification and characterization of variants of acyl-CoA-binding protein in the bovine liver. AB - Four differently modified forms of acyl-CoA-binding protein (ACBP) were identified in ACBP purified from bovine liver. The majority of the purified ACBP was focused at pH 5.9 in isoelectric focusing and could be shown to be N acetylated ACBP without any further modifications. Two minor peaks were focused at pH 5.25 and 4.85 respectively. Mass spectrometry and sequence determination showed that the pI 5.25 form was acetylated at Lys18 and that the pI 4.85 form was malonylated in the same position. Furthermore, it could be shown that non enzymic glycosylation occurred during purification. The acetylated and malonylated variants of ACBP were only found in adult cattle. PMID- 1622398 TI - Differential polypeptide expression in adipose tissue of lean and obese Zucker rats. Evidence of specifically repressed peptides in 7-day-old pre-obese rats. AB - Using two-dimensional electrophoresis on total extracts of adipose tissue from young lean (Fa/fa) and obese (fa/fa) Zucker rats, we have investigated the existence of early events at the protein level, before obvious obesity. Our results indicate that the two genotypes do not differ at 3 days of age in terms of polypeptide pattern. By 7 days of age, two polypeptides are transiently repressed in the fatty genotype, leading us to suggest their potential involvement in the onset of obesity. However, most of the differences between the lean and obese rats are detected at 30 days of age, characterized by an increase in the accumulation of several peptides in the adipose tissue of obese rats, in good agreement with the multiple biochemical changes previously identified at this stage of the disease. These results present evidence of new peptides that may be of interest in the study of the obesity syndrome. PMID- 1622399 TI - Some properties of murine selenocysteine synthase. AB - Selenocysteine (Scy) was synthesized on natural opal suppressor tRNA(Ser) by conversion from seryl-tRNA. We studied the mechanisms of the synthesis of mammalian Scy-tRNA using hydro[75Se]selenide (H75Se-). We found Scy synthase activity in the 105,000 g supernatant of a murine liver extract. The supernatant was chromatographed on DEAE-cellulose, and the activity was eluted at 0.12 M-KCl. The reaction mixture for synthesis of Scy-tRNA contained suppressor tRNA, serine, ATP, seryl-tRNA synthetase (SerRS), HSe- and the enzyme to synthesize Scy-tRNA. These are all essential for the synthesis of Scy-tRNA. Scy in the tRNA product was confirmed by five t.l.c. systems. The conversion from seryl-tRNA to Scy-tRNA was also confirmed with the use of [14C]- and [3H]-serine. The apparent Km values for the substrates serine, tRNA, ATP and HSe- were 30 microM, 140 nM, 2 mM and 40 nM respectively. The active eluates from DEAE-cellulose contained no tRNA kinase. This result showed that Scy-tRNA was not synthesized through phosphoseryl-tRNA. ATP was necessary when Scy-tRNA was synthesized from seryl-tRNA and HSe-. Therefore ATP is used for not only the synthesis of seryl-tRNA but also for the synthesis of Scy-tRNA from seryl-tRNA. The active fraction from DEAE-cellulose was chromatographed on Sephacryl S-300, but the activity disappeared. However, the activity was recovered by mixing the eluates corresponding to proteins of 500 kDa and 20 kDa. In order to examine the binding of HSe- to proteins, a mixture of the active fraction, H75Se- and ATP was analysed by chromatography on Sephacryl S 300. The 75Se radioactivity was found at the position of a 20 kDa protein in the presence of ATP. Thus the 20 kDa protein plays a role in binding HSe- in the presence of ATP. The 500 kDa protein must have a role in the synthesis of Scy tRNA. There are two natural suppressor serine tRNAs, tRNA(NCA) and tRNA(CmCA), in cell cytosol. The present paper shows that the suppressor tRNA fraction, eluted later on benzoylated DEAE-(BD-)cellulose, is a better substrate with which to synthesize Scy-tRNA. Thus we consider that murine Scy-tRNA is synthesized from a suppressor seryl-tRNA on the 500 kDa protein with the activated HSe-, which is synthesized with ATP on the 20 kDa protein. This mammalian mechanism used to synthesize Scy is similar to that seen in Escherichia coli. PMID- 1622400 TI - Prenylated protein methyltransferases do not distinguish between farnesylated and geranylgeranylated substrates. AB - Proteins that are post-translationally modified by prenylation can be either farnesylated (C-15) or geranylgeranylated (C-20) by separate prenyltransferase enzymes. Prenylated proteins are also methylated at their C-terminal residue by S adenosylmethionine-linked methylation. In this paper we show that the methylation of farnesylated and geranyl-geranylated substrates can be accounted for by the presence of a single enzyme. It is demonstrated that the Km and Vmax. values for the retinal rod outer segment methyltransferase, measured with small molecule farnesylated and geranylgeranylated substrates, are identical. These substrates mutually inhibit each other's methylation, with KI values being equal to their Km values. The Km for S-adenosylmethionine was measured to be the same with either farnesylated or geranylgeranylated substrates. Competitive inhibitors of the methyltransferase containing either a geranylgeranyl or a farnesyl group equally block the methylation of synthetic geranylgeranylated and farnesylated substrates of the enzyme. Importantly, these inhibitors are also equipotent at inhibiting the methylation of the physiological substrates of the rod outer segment methyltransferase. These substrates are both farnesylated and geranylgeranylated. One of these substrates had previously been identified as the farnesylated gamma subunit of transducin. Therefore it appears that the same enzymic activity can methylate both farnesylated and geranylgeranylated substrates. PMID- 1622401 TI - Expression of rat liver NAD(P)H:quinone-acceptor oxidoreductase in Escherichia coli and mutagenesis in vitro at Arg-177. AB - A prokaryotic expression plasmid, pKK-DT2, containing the cDNA of rat liver NAD(P)H:quinone-acceptor oxidoreductase (EC 1.6.99.2; DT-diaphorase) was constructed and used to transform Escherichia coli strain JM109. The rat liver quinone reductase was expressed in strain in JM109 and was inducible with isopropyl beta-D-thiogalactopyranoside (IPTG). The expressed rat protein was purified by affinity chromatography and had kinetic and physical properties identical with the protein purified from rat liver in that it could utilize either NADH or NADPH as the electron donor and its activity was inhibited by dicoumarol. In addition, we have generated four mutants, Arg-177----His (R177H), Arg-177----Ala (R177A), Arg-177----Cys (R177C) and Arg-177----Leu (R177L), using this expression system. Several of the mutants behaved anomalously on SDS/PAGE, but all of the mutant proteins had the expected M(r) as determined by electrospray m.s. These results and those obtained from enzyme kinetic analysis, u.v./visible absorption spectral analysis, and flavin and tryptophan fluorescence analysis of the wild-type enzyme and four mutants indicated that mutations at Arg 177 changed the conformation of the enzyme, resulting in a decrease in enzyme activity. Replacing Arg-177 with leucine altered the protein conformation and decreased FAD incorporation. PMID- 1622402 TI - Duck liver 'malic' enzyme. Expression in Escherichia coli and characterization of the wild-type enzyme and site-directed mutants. AB - A cDNA for duck liver 'malic' enzyme (EC 1.1.1.40) was subcloned into pUC-8, and the active enzyme was expressed in Escherichia coli TG-2 cells as a fusion protein including a 15-residue N-terminal leader from beta-galactosidase coded by the lacZ' gene. C99S and R70Q mutants of the enzyme were generated by the M13 mismatch technique. The recombinant enzymes were purified to near homogeneity by a simple two-step procedure and characterized relative to the enzyme isolated from duck liver. The natural duck enzyme has a subunit molecular mass of approx. 65 kDa, and the following kinetic parameters for oxidative decarboxylation of L malate at pH 7.0: Km NADP+ (4.6 microM); Km L-malate (73 microM); kcat (160 s-1); Ka (2.4 microM) and Ka' (270 microM), dissociation constants of Mn2+ at 'tight' (activating) and 'weak' metal sites; and substrate inhibition (51% of kcat. at 8 mM-L-malate). Properties of the E. coli-derived recombinant wild-type enzyme are indistinguishable from those of the natural duck enzyme. Kinetic parameters of the R70Q mutant are relatively unaltered, indicating that Arg-70 is not required for the reaction. The C99S mutant has unchanged Km for NADP+ and parameters for the 'weak' sites (i.e. inhibition by L-malate, Ka'); however, kcat. decreased 3 fold and Km for L-malate and Ka each increased 4-fold, resulting in a catalytic efficiency [kcat./(Km NADP+ x Km L-malate x Ka)] equal to 3.7% of the natural duck enzyme. These results suggest that the positioning of Cys-99 in the sequence is important for proper binding of L-malate and bivalent metal ions. PMID- 1622403 TI - Alterations in the mucosal processing of iron in response to very-short-term dietary iron depletion and repletion. AB - The transfer of control rats to a low-iron diet for only 24 h resulted in a 2 fold increase in iron uptake by brush-border membrane vesicles. Extension of the low-iron feeding period to 72 h or 2 weeks resulted in only small additional increases in iron uptake by vesicle preparations. In contrast, the transfer of iron-deficient rats to a control diet resulted in a progressive decrease in iron uptake by vesicles that reached a level equivalent to that of control rats in 2 weeks. 59Fe labelling of detergent extracts of these vesicle preparations provided evidence for the presence of an iron-binding protein composed of subunits of 52,000 Da. The changes in the 59Fe labelling of this protein component were consistent with the changes observed in iron uptake by intact brush-border membrane vesicles. The 59Fe-labelling profiles of mucosal ferritin and transferrin from a test dose also were changed substantially in response to very-short-term alterations in dietary iron. Even though changes in dietary iron rapidly altered iron uptake by brush-border membrane vesicles and the incorporation of 59Fe from the test dose into mucosal transferrin, changes in the incorporation of 59Fe into mucosal ferritin best reflected the actual changes in the transfer of iron from dose to plasma. PMID- 1622404 TI - Characterization of two dipeptidases purified from hepatic schistosome egg granulomas in mice. Leukotriene D4 hydrolases of granulomatous tissue. AB - Extracts prepared from tissue with granulomatous inflammation experimentally produced in liver of CBA-strain mice showed increased hydrolysis of leukotriene D4 (LTD4), Leu-Leu and Ala-Gly as compared with normal hepatic cells. Two dipeptidases, Leu-Leu dipeptidase and Ala-Gly dipeptidase, were purified from hepatic granulomas, and quantitative conversion of LTD4 into leukotriene E4 (LTE4) by both enzymes was demonstrated. M(r) values of the purified enzymes were 178,000 for Leu-Leu dipeptidase and 183,000 for Ala-Gly dipeptidase. The enzymes showed homogeneity, appearing as a single band on SDS/PAGE, and the M(r) values of the subunits were 56,000 and 57,000 for Leu-Leu and Ala-Gly dipeptidase respectively. The amino acid compositions of the two enzymes differed considerably from each other. The activity of Leu-Leu dipeptidase was inhibited by bestatin and captopril and stabilized with MnCl2. The Km for LTD4 was 25 microM with a V(max.) of 49.0 mumols/min per mg. In contrast, the activity of Ala Gly dipeptidase was inhibited by cilastatin, cytinylglycine, EDTA and dithiothreitol, and also by captopril. The Km for LTD4 was 5.3 microM with a V(max.) of 50.4 mumols/min per mg. The findings indicate that the conversion of LTD4 into LTE4 by microsomal dipeptidases is elevated during granulomatous tissue reaction. This enzyme activity may become useful for biochemical quantification of the pathological tissue reaction that occurs in organized granulomas. PMID- 1622405 TI - Direct demonstration that increased phosphorylation of 3-hydroxy-3-methylglutaryl CoA reductase does not increase its rate of degradation in isolated rat hepatocytes. AB - Increased phosphorylation of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase has been suggested to target the protein towards an increased rate of degradation. Our previous observations [Zammit & Caldwell (1990) Biochem. J. 269, 373-379] suggested that, although Ca(2+)-mobilizing hormones and other effectors can alter both the phosphorylation state of the enzyme and its total activity in isolated rat hepatocytes, there appears to be no causal correlation between the two parameters. In the present paper we set out to make direct measurements of the specific rate of degradation of 35S-labelled HMG-CoA reductase in hepatocytes treated with agents that produced very marked and prolonged increases in the degree of phosphorylation of the protein, through different mechanisms. Okadaic acid (which inhibits phosphatases 1 and 2A), fructose (which increases cellular AMP through its metabolism to fructose 1-phosphate) and the Ca2+ ionophore A23187 (which also raises cellular AMP through an unknown mechanism) were all unable to alter the rate of HMG-CoA reductase degradation. We conclude that the basal rate of degradation of HMG-CoA reductase is unaffected by its phosphorylation state and that a transiently increased degree of phosphorylation cannot be the mechanism through which mevalonate increases the rate of degradation of the enzyme in rat hepatocytes and other cell types. PMID- 1622406 TI - Oligomeric tumour necrosis factor alpha slowly converts into inactive forms at bioactive levels. AB - The stability of oligomeric human tumour necrasis factor alpha (TNF) at bioactive levels has been studied by two immunoenzymatic assays: one able to specifically detect oligomeric and not monomeric TNF (O-e.l.i.s.a.) and the other able to detect both forms (OM-e.l.i.s.a.). The selectivity of O-e.l.i.s.a. and OM e.l.i.s.a. for oligomeric and monomeric TNF was demonstrated with isolated forms prepared by partial dissociation of recombinant TNF with 10% (v/v) dimethyl sulphoxide and gel-filtration h.p.l.c. Evidence for instability of oligomeric TNF were obtained in physiological buffers, as well as in serum and cell-culture supernatants, as a function of TNF concentration. In particular, only a half of the TNF antigen was recovered in the oligomeric form after 72 h incubation (37 degrees C) at 0.12 nM, whereas no apparent dissociation was detected at 4 nM. The structural changes observed at picomolar concentrations were rapidly reversed by raising the concentration of TNF to about 2 nM by ultrafiltration, suggesting that subunit dissociation and reassociation reactions occur in the picomolar and nanomolar range respectively. The cytolytic activity of L-M cells correlates with oligomeric-TNF levels after incubation at picomolar concentrations. Moreover, isolated oligomeric TNF was cytotoxic towards L-M cells, whereas monomeric TNF was virtually inactive. In conclusion, the results suggest that bioactive oligomeric TNF is unstable at picomolar levels and slowly converts into inactive monomers, supporting the hypothesis that quaternary-structure changes in TNF may contribute to the fine regulation of TNF cytotoxicity. PMID- 1622408 TI - Mechanism of action of purpuromycin. PMID- 1622407 TI - Functional implications of tyrosine protein phosphorylation in platelets. Simultaneous studies with different agonists and inhibitors. AB - During activation of platelets by agonists, a number of proteins become phosphorylated at tyrosine residues. Using immunoblotting with a monoclonal anti phosphotyrosine antibody, we have compared the different phosphotyrosine-protein (PTP) profiles of platelets stimulated with thrombin, collagen, ADP, arachidonic acid, phorbol myristate acetate and P256, an anti-glycoprotein-IIb-IIIa (GPIIb IIIa) monoclonal antibody (mAb). Only a few PTPs were observed in resting platelets, of molecular masses 130, 64, 56-60 and 36 kDa. After stimulation by different agonists these proteins were more intensely phosphorylated and additional PTPs appeared with molecular masses of 170, 150, 140, 120, 105/97 (doublet), 85, 80, 75 and 45 kDa. The kinetics of phosphorylation differed from one agonist to another, but no significant differences in the overall patterns were detected, except in presence of ADP and P256-F(ab')2, which induced only the additional tyrosine phosphorylation of the 64 kDa protein and to a lesser extent that of a 75 kDa protein. The use of various agonists and the inhibitors (staurosporine, ajoene and RGDS) permitted a better characterization of the relationship between the different steps of activation and phosphorylation on tyrosine residues. The studies suggest the following conclusions: (i) stimulation of tyrosine phosphorylation occurs after activation of protein kinase C; (ii) there is a relationship between ligand binding to GPIIb-IIIa and the tyrosine phosphorylation of the 64 kDa protein; and (iii) there is a close relationship between PTP formation and the intensity of platelet activation and aggregation. PMID- 1622409 TI - The importance of the T cell in initiating and maintaining the chronic synovitis of rheumatoid arthritis. AB - We hope that this short review has produced convincing, although indirect, evidence that in the case of rheumatoid synovitis, the T cell is the conductor of an orchestra playing a tune written by an antigen-presenting cell. The tune develops and becomes modified with time, so that it is difficult to discern with clarity much of the original melody. We believe that it may be possible to substitute a new score that will bring this symphony to a harmonious end. We also strongly believe that this is preferable to augmenting the string section or suppressing the percussion section of the orchestra in the vain hope that in the end harmony can be achieved. The final musical analogy must be the hope that the first page of the score can be found, so that we may discover the main theme, the leitmotif, of the rheumatoid-specific antigenic peptide. PMID- 1622410 TI - Precision of the Larsen and the Sharp methods of assessing radiologic change in patients with rheumatoid arthritis. AB - OBJECTIVE: To compare the sensitivity of Sharp's and Larsen's radiographic scoring methods for detecting change in rheumatoid arthritis (RA) over time. METHODS: Radiographs of the hands and wrists were taken at the beginning and at the end of a 2-year followup period, in 42 patients with active RA. Films were scored blindly using both scoring methods. Patients were under treatment with methotrexate (intramuscular injections). RESULTS: Radiographic evidence of progression or amelioration was detected in 25 patients by Larsen's method and in 35 patients by Sharp's method. The relative sensitivity to change over time was greater for Sharp's method (0.01 less than P less than 0.025). CONCLUSION: Sharp's radiographic scoring method seems to be more sensitive to change over time than is Larsen's method. The clinical importance of the change needs to be definitively established. PMID- 1622411 TI - Glucocorticoid receptors in rheumatoid arthritis. AB - OBJECTIVE: Increasing evidence suggests that there is a close interrelationship between the immune system and the hypothalamic-pituitary-adrenal axis. One way these systems are linked is through specific receptor proteins for glucocorticoid hormones in lymphocytes. We sought to determine whether the levels of these receptors differ in patients with rheumatoid arthritis (RA), compared with levels in healthy subjects. METHODS: We determined the density and affinity of lymphocyte glucocorticoid receptors, as well as basal cortisol levels, in 90 patients with active RA and in 200 healthy controls, using a whole cell binding assay. RESULTS: The number of glucocorticoid receptors in RA patients was significantly lower than in controls (mean +/- SD 2,144 +/- 500 per cell versus 5,619 +/- 1,373 per cell; P less than 0.001), whereas there were no differences in binding affinity or cortisol levels. Glucocorticoid receptor density did not correlate with inflammatory disease activity. CONCLUSION: Since glucocorticoids are potent immunosuppressive agents, the decrease in their receptors suggests an impairment of the immune-hypothalamic-pituitary-adrenal axis in patients with RA. PMID- 1622412 TI - Rheumatoid arthritis in Greek and British patients. A comparative clinical, radiologic, and serologic study. AB - OBJECTIVE: To compare the clinical, radiologic, and serologic expression of rheumatoid arthritis (RA) in 2 different populations. METHODS: Standard protocols and assessment criteria were used in this study of 108 Greek and 107 British patients with RA. RESULTS: British patients had more severe articular involvement than did Greeks, as judged by the duration of morning stiffness (P less than 0.005), grip strength (P less than 0.0001), and the numbers of swollen (P less than 0.001) and tender (P less than 0.0001) joints. The British RA patients also had more severe joint damage on radiologic examination, as evidenced by Steinbrocker stage III (P less than 0.005) and IV (P less than 0.025) disease and had more extraarticular manifestations (P less than 0.0001), including rheumatoid nodules (P less than 0.0001) and Raynaud's phenomenon (P less than 0.05). Greek RA patients, however, more frequently presented with sicca manifestations (P less than 0.001) and serum antibodies to Ro/SS-A (P less than 0.025). Furthermore, Ro/SS-A antibodies were associated with a high incidence of side effects to D penicillamine only in the Greeks. CONCLUSION: Genetic and environmental factors may be responsible for these striking differences in disease expression between these 2 European populations with RA. PMID- 1622413 TI - The effect of food on the absorption of methotrexate sodium tablets in healthy volunteers. AB - OBJECTIVE: To examine the effect of food on the absorption and bioavailability of low-dose orally administered methotrexate sodium tablets. METHODS: In this randomized, 2-way crossover study, a 7.5-mg dose of methotrexate (three 2.5-mg tablets) was administered to 12 healthy male volunteers after an overnight fast or within 10 minutes of consuming a high fat-content breakfast. Serum methotrexate concentrations over the next 24 hours were used to determine the area under the concentration-time curve (AUC), the maximum concentration, the time to maximum concentration (tmax), and the serum half-life for each phase. RESULTS: Food delayed the tmax by approximately 30 minutes, but the extent of absorption, as measured by the AUC, for both phases was similar. CONCLUSION: These results demonstrate that the bioavailability of low-dose orally administered methotrexate sodium tablets is not influenced by food. PMID- 1622414 TI - Isolated diffusing capacity reduction in systemic sclerosis. AB - OBJECTIVE: To determine the long-term outcome of patients with systemic sclerosis (SSc) and an isolated reduction in the diffusing capacity for carbon monoxide (DLCO) at the time of initial evaluation. METHODS: Patients with an isolated reduction in DLCO (i.e., normal forced vital capacity [FVC] and normal ratio of the forced expiratory volume in one second [FEV1] to the FVC) on initial evaluation were identified from among 815 patients with SSc who were carefully followed up throughout their illness. We requested that patients have repeat pulmonary function testing (PFT), and the outcomes of these tests, as well as cardiopulmonary and survival outcomes, were determined. RESULTS: An isolated reduction in DLCO, with a normal FVC was detected in 152 (19%) of the 815 patients. A subset of those with an isolated reduction in DLCO (11%) developed isolated pulmonary hypertension and had severely reduced survival rates. Pulmonary hypertension was strongly associated with an initial DLCO of less than 55% of predicted normal and a FVC (% predicted)/DLCO (% predicted) ratio of greater than 1.4. Among all patients in whom this ratio was greater than 1.4, 22% developed isolated pulmonary hypertension, compared with only 2% of those whose ratio was less than 1.4 (P less than 0.01). Of the 152 patients with isolated DLCO reduction, 73 (48%) underwent PFTs a mean of 5.4 years (range 2.0-13.2) after the initial PFT. Only 6 (8%) of these 73 patients ever had serious pulmonary disease: 5 had isolated pulmonary hypertension, and 1 had severe pulmonary fibrosis. Half of the patients with a low initial DLCO demonstrated a significant improvement (greater than 20%) at followup testing that could not be explained by the demographic, clinical, or laboratory findings at the first visit. CONCLUSION: Isolated reduction in DLCO is a frequent abnormality in SSc. Overall, it is associated with a good prognosis for survival and for pulmonary morbidity. A small subset of patients (11%) who have a very low DLCO (less than 55% of predicted) have developed isolated pulmonary hypertension, all of whom had limited scleroderma. PMID- 1622415 TI - Adhesion of peripheral blood mononuclear cells to vascular endothelium in patients with systemic sclerosis (scleroderma). AB - OBJECTIVE: Perivascular infiltrates in skin, subcutaneous tissue, and internal organs are a characteristic feature of early systemic sclerosis (SSc). We studied the first step of migration of peripheral blood mononuclear cells (PBMC) through the vessel wall to the extravascular space, i.e., adhesion of PBMC to endothelial cells (EC), in patients with various forms of SSc (limited scleroderma, diffuse scleroderma, and the transitional form). METHODS: Radioisotope-labeled patient PBMC were coincubated with umbilical cord EC in vitro, and the percentage adhesion was measured. RESULTS: Adhesion of PBMC to EC was markedly decreased, while adhesion of isolated active rosette-forming cells (ARFC) was significantly increased, in SSc patients compared with healthy controls. Decreased adhesion of PBMC to EC was found to correlate with a diminished percentage of ARFC in the peripheral blood. Preincubation of PBMC from healthy donors with interleukin-2 (IL-2) enhanced their adhesion to EC, while preincubation of PBMC from SSc patients with this cytokine resulted in a decrease in adhesion in 10 of 14 individuals. IL-1, interferon-gamma, and transforming growth factor beta had no significant effect on adhesion of SSc patient PBMC to EC. Differences in adhesion of PBMC to EC among the SSc subgroups were not significant. CONCLUSION: Our findings suggest that in SSc, activation of subpopulations of PBMC leads to their enhanced adhesion to vascular endothelium in vivo and to migration of these cells to the extravascular space, resulting in the elimination from the peripheral blood of those PBMC with high ability to adhere to EC. PMID- 1622416 TI - A controlled study of the prevalence of cognitive dysfunction in randomly selected patients with systemic lupus erythematosus. AB - OBJECTIVE: To investigate the prevalence of cognitive dysfunction in randomly selected patients with systemic lupus erythematosus (SLE). METHODS: Randomly selected, ambulatory patients with SLE (n = 49) or with rheumatoid arthritis (RA) (n = 40) completed neuropsychological tests. These included Associate Learning, Switching Attention, Continuous Performance, Associate Recall, Hand-Eye Coordination, Pattern Comparison, Pattern Memory, the Stroop Color and Word Test, and the Symptoms Checklist-90R. Results were evaluated by multiple linear regression analysis. RESULTS: SLE patients had poorer performance than RA patients on the test of attention (P = 0.002) and tests of visuospatial ability (P = 0.03) and P = 0.04), independent of age, education, or steroid use. The conservative level of statistical significance, adjusting for multiple comparisons, was 0.005. SLE patients reported more symptoms of cognitive difficulty. CONCLUSION: Cognitive dysfunction is common in ambulatory SLE patients as measured by standardized tests and is a cause of distress and impaired functioning. Self-reported cognitive difficulty appears to correlate with objective performance. PMID- 1622417 TI - Connective tissue activation. XXXV. Detection of connective tissue activating peptide-III isoforms in synovium from osteoarthritis and rheumatoid arthritis patients: patterns of interaction with other synovial cytokines in cell culture. AB - OBJECTIVE: To determine whether extracts of unincubated osteoarthritis (OA) and rheumatoid arthritis (RA) synovial tissue contain connective tissue activating peptide-III (CTAP-III) isoforms and prostaglandin E2 (PGE2), and whether such extracts have growth-promoting activity, and to determine whether binary combinations of CTAP-III with other cytokines reported to be present in synovial tissue lead to synergistic, additive, or inhibitory effects on growth. METHODS: Acid-ethanol extracts of human synovium were examined for growth-promoting activity by measuring formation of 14C-glycosaminoglycan (14C-GAG) and 3H-DNA in synovial cell cultures; PGE2 was measured by enzyme immunoassay, and CTAP-III isoforms were identified by Western blotting of extracted proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Growth-promoting activity of CTAP-III and other cytokines was tested in synovial cultures treated with the agonists singly and in binary combination, by measuring changes in synthesis of 14C-GAG and 3H-DNA. RESULTS: Platelet-derived CTAP-III and a cleavage isoform with the electrophoretic mobility of CTAP-III-des 1 15/neutrophil-activating peptide-2 (NAP-2) and PGE2 were found in biologically active extracts of synovial samples from patients with RA and OA. Five growth factors (recombinant epidermal growth factor [rEGF], recombinant interleukin-1 beta [rIL-1 beta], basic fibroblast growth factor [bFGF], PGE1, and PGE2) in binary combination with CTAP-III showed synergism in stimulating GAG synthesis; two (recombinant platelet-derived growth factor type BB [rPDGE-BB] and recombinant transforming growth factor beta [rTGF beta]) had an additive effect. In combination with CTAP-III, rEGF and rPDGF-BB had a synergistic effect in promoting DNA synthesis, rTGF beta and rbFGF had an additive effect, and rIL-1 beta, PGE1, and PGE2 were antagonistic. CONCLUSIONS: The results suggest that, in addition to endogenous factors, CTAP-III and other platelet-derived cytokines may play roles in regulating synovial cell metabolism in RA and OA, and that combinations of growth factors may be more significant than single agents in amplification or suppression of important cell functions. PMID- 1622418 TI - Are we losing focus on the internal elastic lamina in giant cell arteritis? PMID- 1622419 TI - Type X collagen synthesis in human osteoarthritic cartilage. Indication of chondrocyte hypertrophy. AB - OBJECTIVE: To investigate the appearance of hypertrophic chondrocytes in osteoarthritic (OA) cartilage, using type X collagen as a specific marker. METHODS: The biosynthesis of type X collagen was examined by metabolic labeling of freshly isolated articular chondrocytes with 3H-proline, immunoprecipitation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the synthesized collagens. Extracellular deposition of types X and II collagen was analyzed immunohistochemically. RESULTS: Immunostaining revealed an irregular distribution of type X collagen, which was localized around chondrocyte clusters in fibrillated OA cartilage, but was absent from the noncalcified region of normal articular cartilage. Freshly isolated OA chondrocytes synthesized predominantly type X collagen, while control chondrocytes synthesized mostly type II collagen. CONCLUSION: Our findings indicate focal premature chondrocyte differentiation to hypertrophic cells in OA cartilage. PMID- 1622420 TI - Progressive aortic valve inflammation occurring despite apparent remission of relapsing polychondritis. AB - We describe a patient with relapsing polychondritis in whom aortic valve inflammation developed 3 years after diagnosis, when the polychondritis had been in apparent remission for an extended period of time. Infection and cardiac involvement can be significant complications of relapsing polychondritis. Recommendations for monitoring and treatment of patients with this disease are discussed. PMID- 1622421 TI - Antibodies to glycyl-transfer RNA synthetase in patients with myositis and interstitial lung disease. AB - OBJECTIVE: We have previously described anti-EJ antibodies, and provided evidence that these antibodies react with glycyl-transfer RNA (gly-tRNA) synthetase. The aim of the present study was to identify patients with anti-EJ antibodies and describe the clinical associations of the antibody, in particular, whether it is associated with the syndrome of myositis and interstitial lung disease (ILD) that has been previously associated with autoantibodies to the aminoacyl-tRNA synthetases for histidine, threonine, and alanine. METHODS: Sera from patients with suspected or proven polymyositis or dermatomyositis (DM), sera with anticytoplasmic patterns, and control sera were tested for anti-EJ antibodies by immunoprecipitation (IPP). Positive sera and controls were tested for the ability to inhibit gly-tRNA synthetase by preincubation of the enzyme source with the serum. RESULTS: Anti-EJ antibodies were demonstrated in the sera of 5 patients, by IPP of characteristic tRNAs and protein. Original serum EJ and each of the new sera significantly inhibited the enzymatic activity of gly-tRNA synthetase but not histidyl-tRNA synthetase. All 5 of the new patients had inflammatory myopathy, a typical DM rash, and ILD. One, who had an overlap syndrome with systemic lupus erythematosus, had anti-EJ at least 4 months before the development of clinical myositis. Arthritis and Raynaud's phenomenon, other features associated with antisynthetases, were also seen. CONCLUSION: Anti-EJ is associated with the syndrome of myositis and lung disease that is seen in association with other antisynthetases. The finding of specific inhibition of gly tRNA synthetase by all anti-EJ-positive sera strongly supports the identification of EJ antigen as gly-tRNA synthetase. PMID- 1622422 TI - FDA Arthritis Advisory Committee meeting: guidelines for clinical evaluation of therapies for scleroderma. PMID- 1622423 TI - Does tumor necrosis factor protect against lupus in west Africans? PMID- 1622424 TI - Relationship between interleukin-6 levels and platelet counts in systemic juvenile rheumatoid arthritis: comment on the article by De Benedetti et al. PMID- 1622425 TI - Comment on the study of deflazacort versus prednisone in the treatment of chronic inflammatory disorders. PMID- 1622426 TI - Pharmacologic desensitization by intravenous protocols. PMID- 1622427 TI - Interpreting brain scans of lupus patients taken after seizures or migraines. PMID- 1622428 TI - The use of classification criteria in the diagnosis of rheumatoid arthritis: comment on the article by Katz and Liang. PMID- 1622429 TI - DR-DQ variants in rheumatoid arthritis and Felty's syndrome: comment on the article by Wallin et al. PMID- 1622430 TI - Entry criteria influence conclusions about rates of flare in lupus pregnancy: comment on the article by Petri et al. PMID- 1622431 TI - Levofloxacin, a new quinolone antibacterial agent. An introductory overview. PMID- 1622432 TI - Levofloxacin (DR 3355), a new quniolone antibacterial agent. PMID- 1622433 TI - Acute oral toxicity of the new quinolone antibacterial agent levofloxacin in mice, rats and monkeys. AB - Acute oral toxicity of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4- methyl-1 piperazinyl)-7-oxo-7H-pyrido [1,2,3-de][1,4]benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4), a new quinolone antibacterial agent, was studied in ddy mice, SD rats and cynomolgus monkeys. LD50 values were 1,881 mg/kg for males and 1,803 mg/kg for females in mice, 1,478 mg/kg for males and 1,507 mg/kg for females in rats and more than 250 mg/kg in females monkeys. Toxic signs included the decrease in locomotor activity, ptosis, tremor, tonic convulsion and respiratory depressed in rodents and soft feces or vomiting in monkeys. At necropsy, no treatment-related changes were observed in any species except for the enlargement of the cecum in rats. PMID- 1622434 TI - Twenty-six-week oral toxicity of the new quinolone antibacterial agent levofloxacin in rats and cynomolgus monkeys. AB - The oral 26-week toxicity of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4- methyl 1-piperazinyl)-7-oxo-7H-pyrido [1,2,3-de][1,4]benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4) was investigated in rats and monkeys. Rats receiving higher doses of DR-3355 exhibited an increased number of larger fecal pellets, salivation, lower neutrophil counts, enlargement of the cecum and prominent goblet cells in the cecal mucosa. Monkeys did not show any changes due to DR-3355 treatment. Therefore, a no-effect dose of DR-3355 under these conditions was determined as 20 mg/kg in the rat and 62.5 mg/kg in the cynomolgus monkey. PMID- 1622435 TI - Reproductive toxicity of the new quinolone antibacterial agent levofloxacin in rats and rabbits. AB - The reproductive toxicity of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4- methyl 1-piperazinyl)-7-oxo-7H-pyrido [1,2,3-de][1,4]benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4) was investigated in rats and rabbits. DR-3355 was administered orally prior to and in the early stage of pregnancy to male and female rats at doses of up to 360 mg/kg. No adverse effects on fertility or teratogenicity were noted at any dose. DR-3355 elicited no evidence of teratogenicity when administered during the fetal organogenesis period to pregnant rats at doses of up to 810 mg/kg, or to pregnant rabbits at doses of up to 50 mg/kg. However, female rats receiving 810 mg/kg showed salivation, soiled coats, soft stools and decreases in body weight and food intake. Rat fetuses in the 810 mg/kg group exhibited decreased body weight and retardation of ossification, and showed increases in mortality and skeletal variations. Decreases in maternal body weight and food intake were observed in rabbits in the 50 mg/kg group. No adverse effects were observed in perinatal and postnatal toxicity studies in rats using doses of up to 360 mg/kg. PMID- 1622436 TI - Mutagenicity of the new quinolone antibacterial agent levofloxacin. AB - A new quinolone antibacterial agent (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10- (4 methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6- carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4), was studied for mutagenicity using the following short-term in vitro and in vivo tests. 1. IN VITRO STUDIES: reverse mutation test (Ames method) on S. typhimurium and E. coli; and HGPRT forward mutation test, cytogenetic test, and sister chromatid exchange (SCE) test, all on Chinese hamster cells. 2. In vivo studies: mouse micronucleus test, SCE test on mouse bone marrow cell, in vivo-in vitro unscheduled DNA synthesis (UDS) test on rat primary hepatocytes, and dominant lethal test in BDF1 mice. In the in vitro tests for SCE and for chromosomal aberration, DR-3355 gave dose-dependent positive responses, but no mutagenicity was observed in the same indicators of the in vivo studies, even at the maximum tolerated doses. This strongly suggested that DR-3355 would have no mutagenic effects when used in the treatment of infectious diseases. DR-3355 did not show any positive response in the reverse mutation test, the HGPRT mutation test, the in vivo-in vitro UDS test or the dominant lethal test. These results suggest that chemotherapy with DR-3355 should have no mutagenic effect in man. PMID- 1622437 TI - Antigenicity of the new quinolone antibacterial agent levofloxacin. AB - An antigenicity study of a new quinolone antibacterial agent, (-)-(S)-9-fluoro 2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo- 7H-pyrido[1,2,3 de][1,4]benzoxazine-6-carboxylic acid hemihydrate (lefovloxacin, DR-3355, CAS 100986-85-4), was carried out in mice, guinea pigs and rabbits with passive cutaneous anaphylaxis (PCA), systemic anaphylaxis (SA) and enzyme linked immunosorbent assay (ELISA). Mice were sensitized with DR-3355 (1-100 mg/kg) or DR-3355-ovalbumin (OA) conjugate (DR-3355-OA; 500 micrograms/kg). No IgE antibodies to DR-3355 were detected in the sera obtained from the DR-3355 sensitized mice, indicating that DR-3355 has no immunogenicity in mice. By using DR-3355-OA as a sensitizing antigen, DR-3355-specific IgE was produced successfully in 7 out of 10 sera, and 4 sera showed positive responses in 24-h PCA on intravenous injection of DR-3355 (40 mg/kg). These responses disappeared on challenge with a dose of 2.5 mg/kg. Guinea pigs or rabbits were sensitized with DR-3355 (2-100 or 2-20 mg/kg) or DR-3355-OA (2 mg/kg). No SA was observed in the sensitized guinea pigs after the intravenous injection of DR-3355 (40 mg/kg). No antibodies to DR-3355 were detected in the sera obtained from the sensitized guinea pigs and rabbits by PCA or ELISA. These results suggest that DR-3355 may not possess antigenicity in guinea pigs and rabbits. On the other hand, the results of PCA in mice suggest that DR-3355 may have eliciting antigenicity potential. PMID- 1622438 TI - Effect of the new quinolone antibacterial agent levofloxacin on multiple organ carcinogenesis initiated with wide-spectrum carcinogens in rats. AB - A multiple organ carcinogenesis model was used in male F344 rats to test the carcinogenic potential of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1 piperazinyl)-7-oxo- 7H-pyrido[1,2,3-de][1,4] benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 10086-85-4). After sequential treatment with diethylnitrosamine (DEN: carcinogen for the liver), N-methylnitrosourea (MNU: carcinogen for the esophagus, forestomach and thyroid) and dihydroxy-di-N propylnitrosamine (DHPN: carcinogen for the lungs, kidney and urinary bladder), rats were treated with DR-3355, N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN), N methyl-N'-nitro-N-nitrosoguanidine (MNNG), catechol (CC) or phenobarbital (PB) to examine whether these compounds modified the carcinogenesis in multiple organs. As a result of histopathological examinations at study week 20, DR-3355 did not induce neoplastic lesions, nor did it enhance the occurrences of proliferative preneoplastic lesions. In contrast, BBN increased the incidences of hyperplasias and papillomas of the urinary bladder. CC enhanced the occurrences of hyperplasias and papillomas of the forestomach as well as submucosal glandular growth for the glandular stomach. PB increased the number of altered cell foci in the liver and the incidence of follicular cysts and hyperplasias of the thyroid. These results indicate that DR-3355 is not capable of promoting the development of tumors in rat multiple organs. PMID- 1622439 TI - Lack of nephrotoxic effects of the new quinolone antibacterial agent levofloxacin in rabbits. AB - The nephrotoxicity of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1- piperazinyl)-7-oxo-7H-pyrido [1,2,3-de][1,4]benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4), a new quinolone antibacterial agent, was evaluated in male New Zealand White (NZW) rabbits after oral administration of 30 or 120 mg/kg for 10 days. Although reduced body weight gain was observed in the 120 mg/kg, DR-3355 induced no change in function and morphology of the kidneys at both doses. PMID- 1622441 TI - Phototoxic potential of the new quinolone antibacterial agent levofloxacin in mice. AB - The phototoxic potential of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4- methyl-1 piperazyl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6- carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4) was evaluated by the mice ear swelling reaction. Results were compared with those for enoxacin (ENX). Mice were orally administered DR-3355 or ENX and immediately exposed to ultraviolet-A for 4 h. Phototoxicity was determined by measuring ear thickness developing 24 h after irradiation. DR-3355 provided no changes in the ear at 200 mg/kg, but caused ear swelling at 800 mg/kg. ENX caused severe phototoxicity in a dose dependent manner from 50 mg/kg. These data suggest that DR-3355 has minor phototoxic potential, but is approximately 4-fold less toxic than ENX in these experimental conditions. PMID- 1622440 TI - Ophthalmotoxicity and ototoxicity of the new quinolone antibacterial agent levofloxacin in Long Evans rats. AB - An ophthalomo- and ototoxicity study of a new quinolone antibacterial agent, (-) (S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1- piperazinyl)-7-oxo-7H pyrido[1,2,3-de] [1,4]benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR 3355, CAS 100986-85-4) was investigated in Long Evans rats. The rats were orally administered 100 mg/kg of DR-3355, ciprofloxacin (CPFX), norfloxacin (NFLX) or nalidixic acid (NA) for 2 weeks, and the effects on visual and auditory functions were examined. Examination of electroretinograms (ERGs) revealed a decrease in the amplitudes of the a- and b-waves, a prolongation of the latency and diminution or disappearance of oscillatory potential waves in NA treated rats. Similar but milder changes were also noted in the NFLX treated rats. ERGs from DR 3355 or CPFX treated rats were normal. Histopathological examination revealed no changes suggestive of ophthalmotoxicity or ototoxicity in the rats treated with DR-3355, CPFX or NFLX. On the other hand, NA treated rats showed partial loss of the outer hair cells of the organ of Corti in the cochlea, suggesting that NA had slight ototoxicity. DR-3355 did not show any deleterious visual or auditory effects at the dose used in this study. PMID- 1622442 TI - Interaction of the new quinolone antibacterial agent levofloxacin with fenbufen in mice. AB - The interaction of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1- piperazinyl)-7-oxo-7H-pyrido[1,2,3-de] [1,4]benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4) with fenbufen, a nonsteroidal anti-inflammatory agent, in mice was assessed by convulsive seizure and subsequent death in comparison with that of other new quinolones such as DR 3354 (the R-(+)-isomer of ofloxacin), ofloxacin, norfloxacin, enoxacin and ciprofloxacin. Although treatment with each quinolone or fenbufen alone at a dosage level tested in mice showed no changes, coadministration of a large dose of all quinolones and fenbufen caused convulsant death. When compared with the severity of this interaction, it was in the order of enoxacin greater than norfloxacin greater than ciprofloxacin greater than DR-3354 greater than ofloxacin greater than or equal to DR-3355 under these experimental conditions. PMID- 1622444 TI - Get involved: multiculturally. PMID- 1622443 TI - General pharmacology of the new quinolone antibacterial agent levofloxacin. AB - The general pharmacological properties of (-)-(S)-9-fluoro-2,3-dihydro-3- methyl 10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4] benzoxazine-6 carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4), an optically active isomer of ofloxacin, were examined. 1. Central nervous system (CNS): DR-3355 at 200-600 mg/kg p.o. showed depressant activity on the CNS, as was indicated by the depressant syndrome (mice), decreased spontaneous motor activity (mice) and hypothermia (mice and rabbits). In the cat behavior and EEG experiments, it had both stimulant and depressant effects at 30-100 mg/kg i.p., and caused transient slow waves followed by seizures at 20-30 mg/kg i.v. DR-3355 had no effect on convulsion, hexobarbital anesthesia, pain reaction to a tail pinch, or conditioned avoidance response, except that it showed mild analgesic activity in acetic acid writhing at 600 mg/kg p.o. 2. Respiratory and cardiovascular system: DR-3355 produced a hypotensive and a bradycardiac effect after the rapid i.v. injection of 6 mg/kg or more in anesthetized dogs, accompanied by an increase in plasma histamine concentration. Both changes were markedly reduced when the test drug was administered by continuous i.v. infusion. 3. Autonomic nervous system: DR-3355 inhibited nictitating membrane contraction induced by both pre- and post-ganglionic stimulation, and inhibited the depressor response to acetylcholine at 20 mg/kg i.v. It had no influence on pupil size or on pressor response to norepinephrine. 4. Gastrointestinal system: DR-3355 at 600 mg/kg p.o. inhibited gastric secretion. Dog gastrointestinal motility was slightly inhibited, and was then stimulated over the dose range of 2-20 mg/kg i.v. It had no influence on gastrointestinal propulsion, the gastric emptying rate or the gastric mucosa. 5. Isolated smooth muscle: At a concentration of 5 x 10(-4) g/ml, DR-3355 was devoid of spasmogenic or smasmolytic activity, except for showing a slight relaxation effect (trachea), inhibition of nicotine-induced contraction (ileum) and spontaneous or oxytocin-induced motility (pregnant uterus). 6. Miscellaneous: DR-3355 inhibited the urine output and carrageenin induced paw edema at 600 mg/kg p.o. It had no effect on skeletal muscle contraction or the corneal reflex. PMID- 1622446 TI - National health reform: a national debate. PMID- 1622445 TI - Use of laryngeal imaging procedures. PMID- 1622447 TI - Undergraduate education. The beginning of the educational continuum. PMID- 1622448 TI - The AuD discussion. PMID- 1622449 TI - The AuD discussion. PMID- 1622450 TI - The AuD discussion. PMID- 1622451 TI - The AuD discussion. PMID- 1622452 TI - The AuD discussion. PMID- 1622454 TI - Make room for language. PMID- 1622453 TI - The AuD: another approach. PMID- 1622455 TI - Support for AuD. PMID- 1622456 TI - Support for AuD. PMID- 1622457 TI - Support for AuD. PMID- 1622458 TI - Animal research. PMID- 1622459 TI - New RPO. PMID- 1622460 TI - Vision screening. PMID- 1622461 TI - A new pocket camera with macro facility. PMID- 1622462 TI - HIV scheme. PMID- 1622463 TI - Vasospasm and transient monocular blindness. PMID- 1622464 TI - Re: Postoperative follow-up of patients with colorectal cancer. PMID- 1622465 TI - "Fast track" admission for acute myocardial infarction. PMID- 1622466 TI - Topical application of bichloroacetic acid. PMID- 1622467 TI - Children and smoking: how doctors can help. PMID- 1622468 TI - Frequent-user subgroups. PMID- 1622469 TI - Overuse syndrome? PMID- 1622470 TI - RBRVS: objections to Maloney, II. PMID- 1622471 TI - A comparison of repair and replacement for mitral stenosis with partially calcified valve. PMID- 1622472 TI - Premedication before antivenom therapy. PMID- 1622473 TI - Lip enlargement. PMID- 1622475 TI - Dysphagia in the elderly. PMID- 1622474 TI - Priority regarding transconjunctival blepharoplasty. PMID- 1622476 TI - Antidiarrhoeal drugs for acute diarrhoea in children. PMID- 1622477 TI - Airs, waters, places, and doctors. PMID- 1622478 TI - Bronchodilator treatment in asthma: continuous or on demand? PMID- 1622479 TI - Sexual selection and MHC genes. PMID- 1622480 TI - Conduction block in vasculitic neuropathy. PMID- 1622481 TI - Histochemistry of tartrate-resistant acid phosphatase and carbonic anhydrase isoenzyme II in osteoclast-like giant cells in bone tumours. PMID- 1622482 TI - Is pentane produced by colonic bacteria? PMID- 1622483 TI - Colonic motility and functional diarrhea. PMID- 1622484 TI - Seidlmayer's syndrome: postinfectious cockade purpura of early childhood. PMID- 1622485 TI - Few are malingering. PMID- 1622486 TI - Neurobehavioral sequelae of fetal cocaine exposure. PMID- 1622487 TI - Re: Odontogenic myxoma. Report of a periodontally-located case. PMID- 1622488 TI - The association of antiphospholipid antibodies with pregnancies complicated by fetal growth restriction. PMID- 1622489 TI - Orbital inflammation and inflammatory bowel disease. PMID- 1622490 TI - Treatment of tendonitis in horses. PMID- 1622491 TI - Provocative test for chronic mesenteric ischemia. PMID- 1622492 TI - Severe endobronchial hemorrhage. PMID- 1622493 TI - 'Orthodontic relapse'. PMID- 1622494 TI - Acute infectious erythemas in children. PMID- 1622495 TI - Statistical aspects of research methodology. PMID- 1622496 TI - Report of a national workshop on screening for cancer of the cervix. PMID- 1622497 TI - Effects of digitalis and dobutamine. PMID- 1622498 TI - Effects of amrinone in patients recovering from cardiac surgery. PMID- 1622499 TI - Study of aortic stenosis. PMID- 1622500 TI - Total peripheral parenteral nutrition in pregnancy. PMID- 1622501 TI - New schizophrenia booklet. PMID- 1622502 TI - Effect of alcohol on action myoclonus in Lance-Adams syndrome and progressive myoclonus epilepsy. PMID- 1622503 TI - Confidential HIV testing. PMID- 1622504 TI - Cholesterol screening. PMID- 1622505 TI - The understandings of common health terms by doctors, nurses and patients. PMID- 1622506 TI - Contemporary results of carotid endarterectomy. PMID- 1622507 TI - Residual intrascleral and intraretinal melanoma. A concern with lamellar sclerouvectomy for uveal melanoma. PMID- 1622508 TI - Anterior uveitis and hypopyon. PMID- 1622509 TI - Diabetic ketoacidosis in an Addis Abeba children's hospital. AB - A retrospective study was carried out to determine the precipitating factors and clinical profiles of diabetic ketoacidosis (DKA) among 46 paediatric patients (mean age 9 yrs) with 52 episodes admitted to the Ethio-Swedish Children's Hospital (ESCH) from January 1, 1982 to December 30, 1988. Thirty (58%) episodes occurred in newly diagnosed diabetics and 22 (42%) episodes in known diabetics. The most common precipitating factors were infection (52%), omission of insulin (16%) and parasitic infection (12%). The mortality rate was 6%, with all fatal cases occurring in previously undiagnosed diabetics. Several of these episodes of DKA may have been prevented by prompt and effective treatment of infections and proper health education. PMID- 1622510 TI - Changes in sexual behavior and condom use associated with a risk-reduction program--Denver, 1988-1991. AB - Human immunodeficiency virus (HIV) risk-reduction programs have been developed to discourage homosexual/bisexual men (i.e., men who have sex with men) from engaging in anal and oral sexual intercourse with partners who are infected with HIV or whose infection status is unknown (1). The consistent and proper use of latex condoms with adequate lubrication may reduce the risk for HIV transmission during intercourse (2). To assist these men in understanding and following "safer" sexual behaviors, the Denver Disease Control Service conducted a longitudinal cohort study as part of CDC's Demonstration Projects for HIV Prevention and Risk Reduction. This report describes the effects of individual counseling sessions--including a basic introduction to the availability and proper use of condoms and lubricants--on short- and long-term behavior change among a group of homosexual/bisexual men in Denver during 1988-1991. PMID- 1622511 TI - Role of human fetal ependyma. AB - Fetal ependyma is an active secretory structure for the programming of developmental events, including the arrest of neuronogenesis, the guidance of axonal growth cones, motor neuron differentiation, and probably also the maintenance and transformation of radial glial cells that guide migratory neuroblasts. The floor plate, induced by the notochord, is the first part of the neuroepithelium to differentiate. It establishes polarity and growth gradients of the neural tube and has immunohistochemical features that differ from all other regions of the ependyma. The dorsal and ventral median septa, formed by floor and roof plate ependymal processes, prevent aberrant decussations of developing long tracts, but permit the passage of commissural axons. Fetal ependyma synthesizes several intermediate filament proteins absent from mature ependymal cells, although some are also expressed in undifferentiated neuroepithelial cells. Fetal ependyma also produces diffusible molecules, such as neural cell adhesion molecule, proteoglycans, nerve growth factor, and S-100 protein, all in specific temporal and spatial distributions. Maturation of the ependyma is not complete until the postnatal period. An abnormal fetal ependyma may play a primary role in the pathogenesis of some cerebral malformations, such as lissencephaly/pachygyria and holoprosencephaly. PMID- 1622512 TI - Nephrocalcinosis complicating medical treatment of posthemorrhagic hydrocephalus. AB - Furosemide and acetazolamide are often used concurrently to treat posthemorrhagic hydrocephalus in premature infants with intraventricular hemorrhage. Eleven premature infants with posthemorrhagic hydrocephalus were monitored for the development of hypercalciuria during treatment using urine calcium/creatinine (Ca/Cr) ratios (normal: less than or equal to 0.21). Seven of 11 infants (64%) developed hypercalciuria; 5 of those 7 infants had nephrocalcinosis on renal ultrasonography. Infants who developed nephrocalcinosis had urine Ca/Cr ratios of 0.5-4.0. In all 5 infants with nephrocalcinosis, renal calculi decreased and urine Ca/Cr improved after drug therapy was discontinued. The combined use of acetazolamide and furosemide as therapy for posthemorrhagic hydrocephalus places premature infants at high risk for nephrocalcinosis. It is suggested that urine Ca/Cr be monitored closely in infants receiving these drugs and that other treatment modalities be considered when the urine Ca/Cr ratio exceeds 0.21. PMID- 1622513 TI - Developmental change in type VI collagen in human cerebral vessels. AB - Vascular development in the human brain was studied by immunohistochemistry using an anti-type VI collagen antibody. Positive vessels were evident from an early gestational age in the meninges, from 21 weeks gestation in the basal ganglia and deep white matter, and from 38 weeks gestation in the cerebral cortex and superficial white matter; however, type VI collagen never appeared in the subependymal germinal layer. The absent or scarce type VI collagen in the subependymal germinal layer may be one of the important factors of subependymal/intraventricular/periventricular hemorrhage in premature neonates. The earlier appearance of positive vessels in the deep white matter than in the cortex and superficial white matter suggests that the medullary vein develops earlier than the cortical and subcortical veins and arteries. These characteristics of the developing vascular structure may be one cause of perinatal brain damage. PMID- 1622514 TI - Utility of serial EEGs in neonates during extracorporeal membrane oxygenation. AB - We found electroencephalographic (EEG) studies to be useful for monitoring cerebral function, for confirming seizure activity, and for limited prediction of short-term outcome in 145 neonates who required extra-corporeal membrane oxygenation (ECMO) of reversible respiratory failure. The EEG tracings were classified as normal or as mildly, moderately, or markedly abnormal; abnormal recordings were further classified as focal, diffuse, or predominantly lateralized. A significant decrease in frequency and degree of EEG abnormalities was observed in recordings obtained after ECMO compared to those obtained prior to (P = .001) or during ECMO (P = .001). There was no significant increase in marked EEG abnormalities when recordings obtained before and during ECMO were compared (P = 0.41). Of 11 infants with electrographic seizures during ECMO, 7 (64%) either died during their nursery courses or were developmentally handicapped at age 1 year which is a significantly greater adverse outcome than that observed in infants without EEG seizure activity (P less than .003). No consistently lateralized EEG abnormalities were observed during or after ECMO when compared to tracings obtained before cannulation of the right common carotid artery. There was no acute change in EEG rhythm or amplitude over the right cerebral hemisphere during right common carotid artery cannulation. Our observations support the value of serial EEG in the assessment of cerebral function in critically ill infants undergoing ECMO. They further suggest that, in this patient population, cannulation of the right common carotid artery is a safe procedure that does not result in lateralized abnormalities of cerebral electrical activity. PMID- 1622515 TI - Handwringing in Rett syndrome: a normal developmental stage. AB - Handwringing, a characteristic clinical finding in Rett syndrome, appears typically after the loss of hand function. Available data suggest that original hand function never proceeds beyond elementary grasping. Handwringing and hand mouthing are normal developmental stages occurring at about 14 weeks of age in normal infants. The distressed behavior that characterizes the clinical onset of the disorder often turns attention away from the underlying severe apraxia. The confusion is further compounded by the fact that handwringing is also an elementary expression of stress in normal individuals. PMID- 1622516 TI - Internal carotid arterial blood flow velocity in infants. AB - The differences in the velocity and pulsatility indexes in the internal carotid artery were evaluated in 62 normal controls, 42 infants with cerebral palsy, and 22 infants with mental retardation, all within the first year of life. In the normal controls, the average maximal blood flow velocity (A/L), and the maximal end-diastolic flow velocity increased during the first year of life. Pulsatility index decreased significantly between the ages of newborn to 2 mos and 3-5 mos, and remained constant thereafter. Compared with normal controls, the average maximal blood flow velocity and the maximal end-diastolic flow velocity values were significantly reduced in infants with cerebral palsy during the first 6 months of life, while no differences in these values were observed in infants with mental retardation. There were no differences in the pulsatility index values in the 3 subject groups throughout the first year of life. Flow velocity in the internal carotid artery could reflect the status of the cerebral circulation in infants within the first year of life. PMID- 1622517 TI - Etiologies and distribution of neonatal leukomalacia. AB - Neonatal leukomalacia was classified into 4 groups: focal (F), widespread (W), diffuse (D), and multicystic encephalomalacia (MCE) according to the distribution of ischemic necrosis in the cerebral hemisphere. The highest and lowest values of PaCO2, PaO2, and pH and the lowest systolic and diastolic blood pressures were compared among each group and controls. The lowest PaCO2 values were significantly lower in MCE than in the F, W, and D (F + W + D) group or controls. The lowest values of systolic and diastolic blood pressures in the W and F + W + D groups were significantly lower than in the controls; therefore, hypocarbia can be an etiologic factor of MCE rather than periventricular leukomalacia. Hypotension may be closely related to a causal factor of neonatal leukomalacia. PMID- 1622518 TI - Aerobic and anaerobic bacteriology of intracranial abscesses. AB - The bacteriologic and clinical findings of 39 pediatric patients with intracranial abscess are presented. Twenty-three children presented with brain abscess and 16 with subdural empyema. Predisposing conditions were present in all instances. Sinusitis was present in 25 children and 4 patients each had chronic otitis media, dental abscess, and congenital heart disease. The abscess was located in the frontal area in 14 patients, parietal in 13, and temporal in 12. Anaerobic organisms alone were recovered in 22 patients (56%), aerobic bacteria alone in 7 (18%), and mixed aerobic and anaerobic bacteria in 10 (26%) patients. There were 79 anaerobic isolates (2 per specimen). The predominant anaerobes were anaerobic Gram-positive cocci (29 isolates); Bacteroides sp. (12, including 5 Bacteroides fragilis group), Fusobacterium sp. (14 isolates); and Prevotella sp. and Actinomyces sp. (6 isolates each). A total of 17 aerobic or facultative isolates (0.4 per specimen), including 11 Gram-positive cocci and 6 Haemophilus sp., were recovered. Antimicrobial therapy was administered to all patients. Nine patients (i.e., 6 with sinusitis and subdural empyema, 3 with sinusitis and brain abscess) did not respond to antimicrobial therapy and aspiration of the abscess, and required surgical drainage of inflamed sinuses. These findings indicate the major role of anaerobic organisms in the polymicrobial etiology of intracranial abscess in children. PMID- 1622519 TI - Midazolam in treatment of epileptic seizures. AB - Midazolam (Versed), the first water-soluble benzodiazepine, has had widespread acceptance as a parenteral anxiolitic agent. Its antiepileptic properties were studied in adult patients with good results. Midazolam was administered intramuscularly to 48 children, ages 4 months to 14 years, with 69 epileptic episodes of various types. In all but 5 epileptic episodes, seizures stopped 1-10 min after injection. These results suggest that midazolam administered intramuscularly may be useful in a variety of epileptic seizures during childhood, specifically when attempts to introduce an intravenous line in convulsing children are unsuccessful. PMID- 1622520 TI - Neurologic complications in galactosemia. AB - Two siblings, a 27-year-old man and his 24-year-old sister were diagnosed with classic transferase deficiency galactosemia at birth and were treated with strict lactose restriction. Despite well-documented dietary management, both siblings are mentally retarded and manifest a progressive neurologic condition characterized by hypotonia, hyperreflexia, dysarthria, ataxia, and a postural and kinetic tremor. Magnetic resonance imaging revealed moderate cortical atrophy, a complete lack of normal myelination, and multifocal areas of increased signal in the periventricular white matter on T2-weighting. These patients suggest that even with early diagnosis and treatment, individuals with galactosemia may have significant neurologic morbidity with abnormalities of white matter development. This finding raises the possibility of biochemical heterogeneity within the classic transferase deficiency group, as well as the possibility of a lack of available galactose metabolites necessary for glycolipid synthesis causing a disruption of normal myelin development. PMID- 1622521 TI - Hyperekplexia and sudden neonatal death. AB - Fifteen patients with hyperekplexia were identified in 3 families; diagnostic clinical characteristics were defined which allowed for early recognition and treatment. During the first 24 hours of life, spontaneous apnea and sluggish feeding effort were observed. After the first 24 hours, surviving infants exhibited the hyperekplexic startle response to nose tapping. This startle response is characterized by sudden muscular rigidity, feeding-induced oropharyngeal incoordination, and poor air exchange often with apnea, persisting with repetitive nose tapping. Untreated infants experienced recurring apnea until 1 year of age. Three of 15 patients died unexpectedly during the neonatal period. Patients treated with clonazepam (0.1-0.2 mg/kg/day) had no serious apneic episodes and startle reflexes were diminished. The pathophysiologic mechanism for hyperekplexia remains obscure. Electroencephalographic studies were consistently normal. The response to and tolerance of benzodiazepines are striking in newborns and infants and suggest an aberrant central nervous system reflex as the etiology; therefore, hyperekplexia should be considered in the evaluation of neonates and infants with apnea, aspiration pneumonia, episodic muscular rigidity, hyperexcitability, and near-miss sudden infant death syndrome. The need for immediate monitoring of at-risk infants, observation for signs of hyperekplexia, and initiation of clonazepam in these patients are emphasized. Hyperekplexic startle response to nose tapping should be included in the routine examination of all newborns. PMID- 1622522 TI - Benign familial neonatal convulsions: generalized epilepsy? AB - A 3-year-old girl is presented with benign familial neonatal convulsions. She had seizures during the neonatal period and at age 3 months. Seizure manifestations and ictal electroencephalography indicated that she had not experienced generalized seizures but partial seizures, although international classifications of epilepsy define benign familial neonatal convulsions as generalized epilepsy. PMID- 1622523 TI - Pubertal arrest associated with valproic acid therapy. AB - Valproic acid has previously been demonstrated to decrease the secretion of multiple pituitary hormones; however, clinical symptoms associated with decreased hormone secretion have not been described. A girl is reported with complex partial seizures who was treated with valproic acid from age 10 years, 7 months to 12 years, 1 month and during this time had an arrest of both growth and secondary sexual development. Two months after discontinuing valproic acid she had resumption of both pubertal growth and maturation. A prospective controlled study is needed to determine more precisely the effects of valproic acid on growth and development. PMID- 1622524 TI - Autosomal recessive cerebellar hypoplasia and tapeto-retinal degeneration: a new syndrome. AB - Two sisters with autosomal recessive cerebellar hypoplasia and severe nonprogressive retinal pigmentary disease are presented. This syndrome has been previously described in only 1 patient. The retinal changes may be difficult to discern and we suggest that all patients with congenital ataxia have a detailed ophthalmologic assessment, including electroretinography. PMID- 1622525 TI - Asymptomatic cerebral infarction in Kawasaki disease. AB - Meningitis, facial palsy, subdural effusion, and cerebral infarction have been reported to be some of the nervous system complications of Kawasaki disease which usually are clinically obvious. A 22-month-old boy with Kawasaki disease, who developed asymptomatic cerebral infarction, is reported. Hyperpyrexia persisted for 57 days; echocardiography and magnetic resonance imaging revealed the presence of aneurysms in the coronary, axillary, and internal iliac arteries. This study indicates that patients with Kawasaki disease may have silent cerebral infarction. PMID- 1622526 TI - Internal carotid artery occlusion associated with Mycoplasma pneumoniae infection. AB - A 12-year-old girl with serologically-proved Mycoplasma pneumoniae infection developed right-sided hemiparalysis 10 days after the onset of the disease. Cerebral infarction was documented by cranial computed tomography; cerebral angiography revealed left carotid artery occlusion. Cerebrospinal fluid examination was normal. Cerebral infarction is a rare central nervous system complication of M. pneumoniae infection; however, occlusion of the internal carotid artery near the bifurcation has never been demonstrated; therefore, this patient with central nervous system complication of M. pneumoniae infection is unique. PMID- 1622527 TI - Central nervous system tuberculosis. PMID- 1622528 TI - Greenlandization of the Greenland Health Service. PMID- 1622529 TI - Substance abuse among Greenlandic school children. AB - 1934 school children 12 to 19 years of age answered anonymously a questionnaire, which was sent to all towns and the larger settlements in Greenland. The questionnaire was administered by teachers in the classroom to all pupils in grades seven to eleven. The survey was conducted in November 1990. 1557 students were Greenlandic and 377 were Danish. There were 774 Greenlandic boys and 783 girls. There were 208 Danish boys and 169 girls. The questionnaire had questions about age, sex, social background and use of substance. The substances surveyed for were tobacco, alcohol, hashish/marihuana and different substances for sniffing. 26% of the Danish boys and 45% of the Greenlandic boys were smokers compared to 39% of the Danish girls and 61% of the Greenlandic girls. In the 15 19 age group about 75% were smokers. 71% of the smokers smoked more than three cigarettes a day. 87% of the Danish pupils and 63% of the Greenlandic had used alcohol. Greenlandic students had more often used beer than any other beverage, Danish students had wine more often than the Greenlanders. Out of the total 13% of the boys and 4% of the girls regularly took more than ten times 2cc of pure alcohol on each occasion. 6% of the Danish students and 25% of the Greenlandic students had tried sniffing. They mostly used lighter-gas or glue. Boys used sniffing more often than girls. 25% of the Greenlandic students had tried smoking hashish, in the age group 16-17 about 50%. Cigarette smokers more often than non smokers used other substances.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1622530 TI - Men who never married. A socio-medical study in northern Sweden. AB - In a population-based study 50 never-married men aged 40-64 years were compared with 503 similarly aged other men (married, co-habitant, divorced or widowed). The never-married had shorter education than other men, and had been unemployed more often. The never-married mens' emotional relationships were of lower quality. There was modest tendency towards higher blood pressures and higher serum cholesterol levels among the never-married men, but the differences did not reach statistical significance. In conclusion, never-married men were found to be worse off in terms of social support, education, employment status and health knowledge. Differences in health status, however, were small. It is possible that positive factors, not fully elucidated in this study, counterbalance the adverse socio-medical characteristics. Another possibility is that differences will become manifest at an older age which could be surveyed in a follow-up study. PMID- 1622531 TI - Saami and Norwegian clients' use of a treatment facility for drug and alcohol problems in northern Norway. AB - Saami people ("Lapps") and Norwegians make different use of primary health care services, and Larsen and Nergard (1) reported an under-representation of Saami clients at a treatment facility for drug and alcohol problems in Northern Norway in the years 1986-1988. However, Saami and Norwegian groups did not differ in number of days in treatment, number of treatment incidents, mean age or self reported years of problem drinking. Since it is believed that Saami clients are under-represented in Norwegian treatment facilities because of cultural differences, the location of treatment facilities within a Saami municipality was expected to increase the incidence of Saami clients. The present study investigated the incidence of Saami clients at Karasjok treatment facility during 1988 and 1989, 8 and 9 years after the opening of this treatment centre. All clients registered at Finnmark County's treatment facility for drug and alcohol problems during 1988-89 were categorized as either Saami or Norwegian by their language preference. Unfortunately, the Saami group was still under-represented among clients at this treatment facility. In addition, a significant difference in the sex-ratio between the two groups was found, indicating that Saami women do not use the institution at all. Results are discussed in terms of availability of health services for minority groups. PMID- 1622532 TI - Mortality among the Baffin Inuit in the mid-80s. AB - This article proposes to describe mortality among the Inuit of the Baffin region during the 1983-1987 period and to compare it with that of Canadians as a whole. Mortality among the Baffin Inuit is clearly higher than that of the Canadian population as a whole. Life expectancy at birth is 66.6 years, approximately 10 years lower than that for the general Canadian population (76.3 years). Injuries and poisoning, neoplasms, and diseases of the respiratory system are the leading causes of death observed among the Baffin Inuit. For each of these causes, the rates obtained for the Inuit are significantly higher than those for the total population of Canada. PMID- 1622534 TI - Adaptive changes of membrane lipid composition in humans living in the north. AB - Some parameters of red cell membrane lipid composition as well as intensiveness of lipid peroxidation and activity of its regulatory factors were assessed in northern aborigines, newcomers and alcohol abusers. It is proposed that the increased lipid peroxidation is responsible for the cholesterol and monoenic fatty acid accumulation in membranes of all groups studied. The data obtained make it possible to consider the lipid peroxidation as a mechanism for adaptive membrane lipid modification in humans. PMID- 1622533 TI - Primary angle-closure glaucoma and mononuclear blindness. Clinical pattern in 2 Inuit women from Greenland. AB - Primary angle-closure glaucoma (PACG) occurs in various clinical forms and is a permanent challenge for medical personnel responsible for eye care in elderly persons, for medical officers in the Arctic in particular. A clinical report is given of two cases: one with a destructive attack of classical acute glaucoma in a 46 year old woman versus another with a totally symptomless, gradual monocular blindness in a woman, aged 56. In both patients the fellow eye showed incipient chamber angle synechia formation. Peripheral iridectomy has given fully normal fellow eye function in the first woman, now for 22 years. The other had a recent YAG laser iridotomy in her fellow eye. The patients are described on the background of PACG population studies performed in Greenland since the 1960'ies, including gonioscopy and extensive anterior chamber depth measurements as attempts of early PACG detection. PMID- 1622535 TI - An educational program for school nurses caring for the pediatric client with a tracheostomy. Training the school nurse to care for a child re-entering the public education system with a tracheostomy. PMID- 1622536 TI - Pressure ulcers and the elderly. A review of the literature, 1980-1990. PMID- 1622537 TI - Product notebook: a new fecal containment device. A case study describing one use of the Bard FCD fecal containment device. PMID- 1622538 TI - Evaluation and cost analysis of a pressure reduction mattress. One hospital's study of a pressure reduction mattress and its effectiveness. PMID- 1622539 TI - The power to influence politics. PMID- 1622540 TI - Controlling cancer pain with patient-controlled analgesia. PMID- 1622541 TI - Platelets and blood vessels: the adhesion event. AB - Circulating blood platelets attach to damaged blood vessels by specific adhesion molecules. In the human arterial circulation, a unique 'shear-dependent' mechanism governs adhesion by a single receptor-ligand (glycoprotein Ib-von Willebrand factor) pair. Here, Gerald Roth reviews recent data that provide insights into the functions of these molecules. PMID- 1622542 TI - Lymphocyte interactions with endothelial cells. AB - Adhesion of lymphocytes to endothelium is vital to lymphocyte migration into lymphoid tissue and into inflammatory sites. In this review, Yoji Shimizu and colleagues identify the molecules that mediate lymphocyte-endothelial cell adhesion, describe the underlying principles of lymphocyte migration, and discuss a model of the sequence of events that allow a lymphocyte to successfully attach to endothelium and migrate into the surrounding tissue. PMID- 1622543 TI - T-cell-targeted immunotherapy. AB - The pace of T-cell research is matched only by the speed with which fundamental advances are being developed as new therapies. This report from a recent meeting updates developments in a number of immunointervention strategies. PMID- 1622544 TI - A case for chaperones in antigen processing. AB - The assembly of peptide-MHC-class-II molecule complexes by antigen-presenting cells is far more efficient than would be predicted from studies of peptide binding to purified MHC class II molecules in vitro. One possible explanation for this discrepancy is that proteins in the antigen-presenting cell facilitate the assembly process. Here, Diane DeNagel and Susan Pierce present the case for involvement of members of the chaperone/heat shock protein 70 family in the intracellular assembly of processed-antigen-MHC-class-II-molecule complexes. PMID- 1622545 TI - The regulation and function of p21ras in T cells. AB - In T cells, activation of the guanine-nucleotide-binding proteins encoded by the p21ras proto-oncogenes is a common response to triggering of the T-cell antigen receptor, the adhesion molecule CD2 and the receptor for the cytokine interleukin 2. This article by Julian Downward and colleagues describes the mechanisms of p21ras regulation and the potential function of p21ras in T cells, and discusses the evidence that multiple intracellular pathways may be involved in the coupling of cell surface receptors to p21ras. PMID- 1622546 TI - Imaging features of infiltrating renal lesions. PMID- 1622547 TI - CT and MR evaluation of posterior mediastinal masses. PMID- 1622548 TI - Ultrasound of the scrotum. AB - High-resolution real time ultrasound of the scrotum, including gray-scale and color Doppler sonography is presented. The normal anatomy of the scrotum with sonographic correlation is reviewed. The sonographic features of scrotal pathology, including congenital, neoplastic, inflammatory, and traumatic conditions are presented. PMID- 1622549 TI - Behaviourally derived estimates of excitability in striatal and medial prefrontal cortical self-stimulation sites. AB - The refractory periods of the substrate underlying brain-stimulation reward were investigated in three rats with moveable electrodes implanted in the rostral caudate-putamen and the medial prefrontal cortex. Acquisition of caudate-putamen self-stimulation occurred within the first session, while self-stimulation for medial prefrontal cortex was observed only after three sessions of caudate putamen stimulation. The currents required for self-stimulation ranged from 300 to 800 microA (0.1 ms pulse duration) across animals; the maximum response rates averaged roughly 40 bar presses per minute for both structures. Refractory period estimates were obtained from ten caudate-putamen and four medial prefrontal cortex sites. The time course of recovery had the following profile: the curves began to rise at 0.65 ms and 0.95 ms for caudate-putamen and medial prefrontal cortex stimulation, respectively, thereafter increasing to approach an asymptote at 6.00 ms for the caudate-putamen and 6.25 ms for the medial prefrontal cortex. The mean effectiveness value corresponding to the asymptotic portion of the curves was 73% for the caudate-putamen and 69% for the medial prefrontal cortex. Like other forebrain structures, the behaviourally derived refractory periods underlying caudate-putamen and medial prefrontal cortex stimulation, at least at these particular sites, are significantly longer than those observed in most medial forebrain bundle areas, both beginning and ending later. One interpretation for the similarity in their refractory period profiles and the apparent facilitating effect of caudate-putamen stimulation on acquisition of medial prefrontal cortex self-stimulation is that these two regions form part of the same reward substrate. PMID- 1622550 TI - Hippocampal nerve growth factor levels are related to spatial learning ability in aged rats. AB - Brain nerve growth factor (NGF) was determined in two groups of aged rats: 'good' and 'poor' performers. The animals were selected out of a population of 40 aged rats (26-28 months old) trained in a spatial learning task. Animals performing well in the test had significantly higher NGF in the hippocampus when compared to 'poor' performers. No differences in the levels of NGF were found in the cortex, septum and cerebellum. The results implicate hippocampal NGF in cognitive functioning of aged rats, and suggests that the forebrain cholinergic neuronal atrophy which has been observed in cognitively impaired aged rats may be due to reduced availability of target-derived NGF. PMID- 1622551 TI - Muscle activity during unconditioned and conditioned eye blinks in the rabbit. AB - EMGs were recorded from the orbicularis oculi, retractor bulbi and superior rectus muscles in rabbits to investigate the time course of muscle activation during unconditioned and conditioned eye blinks. EMGs from the three muscles showed two responses, with the responses of the orbicularis oculi and retractor bulbi showing the same latency, and the responses of the superior rectus lagging. The latency of responses to periorbital electrostimulation was about 5 ms, and to air puff stimulation about 10 ms. Results showed a tight coupling of activity between muscles, with cross-correlograms peaking at 0.65 to 0.85 and showing little time shift. Stimulus-response curves showed clear non-linearities in the response of the muscle to changes in stimulus strength. Local anesthesia of the cornea had little effect on unconditionally evoked responses. The form of unconditionally evoked responses was similar with periorbital electrostimulation and air puff stimuli but differed in latency. These results show the form of the eye blink reflex response and will be of importance in interpreting electrophysiological studies of the classically conditioned eye blink of rabbits. PMID- 1622552 TI - Motor activity and the mesotelencephalic dopamine function. II. Multivariate analysis of genetically segregating generations. AB - Previous experiments on genetically different inbred strains of mice demonstrated parallel variations between the activity of regional brain tyrosine hydroxylase (TH) and locomotor behavior. Based on these associations, it was hypothesized that genetic variations in mesotelencephalic TH activity, an index of dopamine neurotransmitter function, would correlate positively with exploratory and locomotor behavior. In order to test this hypothesis, open-field motor behaviors and mesencephalic and striatal TH activities were analyzed by multivariate statistical methods in genetically segregating (C57BL/6ByJ X BALB/cJ)F2 and (C57BL/6ByJ X CXBI/ByJ)F2 generations. Factor analysis, based on correlation matrices of variables with significant genetic dominance or additive effects, demonstrated that locomotor activity and frequency of occurrence of various motor patterns were not correlated with mesencephalic and striatal TH activity. These results indicate that the assumption of a positive phenotypic correlation between spontaneous motor activity and mesotelencephalic TH activity does not hold in genetically segregating populations. Strategies and problems in revealing the behavioral consequences of genetically based variations in the mesotelencephalic DA system are briefly discussed. PMID- 1622553 TI - New insights into behavioral evaluation of audiogenic seizures. A comparison of two ethological methods. AB - Wistar male rats were tested for susceptibility to audiogenic seizures (AS) and classified into sensitive (S) and resistant (R) groups by means of a severity index (SI). Susceptible animals were those which displayed wild running behavior (gyri, jumping and atonic falling) followed by generalized tonic-clonic seizures and consequently had an SI = 0.85 (maximum; n = 10). Resistant animals were considered those with no convulsive response to the acoustic stimulation having an SI = 0 (n = 10). Behavioral sequences of susceptible and resistant animals were recorded and analyzed using two ethological methods which basically considered behavior item frequency and statistical interactions of sequential patterns. Both methods include the concept of cluster analysis but do not include a simultaneous analysis of behavior frequency and time spent in each behavior. Thus, a third method is proposed to graphically display both frequency and temporal patterns in a more complex cluster analysis. The methods discussed here allow comparisons of behavioral sequences in a given experimental situation such as susceptible against resistant animals, acute and chronic seizures, comparison of pre- and postdrug effects, etc. Consequently, they may be the micro-behavioral substrate for correlation with contemporary molecular analysis of epileptic seizures. PMID- 1622554 TI - Locomotor development in undernourished rats. AB - The effects of undernutrition on the development of locomotion were studied in fourteen rats. Mothers received about 40% of normal quantities of standard laboratory food from the 5th day of gestation until weaning at the 21st day after birth. Qualitative as well as quantitative aspects of locomotion were studied from the 12th to the 30th day and compared to data from ten control rats. Undernutrition leads to delayed and prolonged developmental changes in locomotion. The adult type of locomotion, which in normal rats develops from the 14th day occurs after the 15th or 16th day in undernourished rats and this development also lasts longer. Locomotion remains mildly abnormal, at least until the 30th day. Especially at lower speeds, walking is clumsy because of an unusual brisk onset, a slightly unsteady gait and non-fluent paw movements. These results are discussed in the perspective of data on brain and muscle development in rats after early undernutrition. PMID- 1622555 TI - Functional dissociation of acute and persistent cognitive deficits accompanying amygdala-kindled seizures. AB - The effects of amygdala-kindled seizures on cognitive function were examined using long-delay flavor-aversion and passive-avoidance conditioning paradigms in rats. Experiments were conducted to compare the functional consequences of unilateral and bilateral kindled seizures (transient deficits) with those due to a kindling history only (persistent deficits). Animals with a history of unilateral or bilateral kindling demonstrated flavor-aversion conditioning that varied inversely with the delay separating saccharin (CS) and lithium (US). Unilateral stimulation during the CS-US interval produced an attenuation of flavor-aversion conditioning that was independent of delay value; bilateral stimulation eliminated conditioning all together. The effects of kindling and kindled seizures on passive-avoidance conditioning were functionally identical. Animals with a history of unilateral kindling demonstrated strong evidence of conditioning with no effect of posttraining seizures. In contrast, animals with a history of bilateral kindling were impaired in a passive-avoidance task. The impairment was evident in the presence or absence of seizure induction during training. Electrographic and behavioral indices of epileptiform activity produced by unilateral and bilateral stimulation failed to reveal any differences in seizure duration or severity. The results support the conclusion that cognitive disruption by amygdala-kindled seizures is task-dependent, does not show a temporal dependence, and cannot be explained on the basis of electrographic or behavioral measures of seizure severity alone. PMID- 1622556 TI - Behavioural strategies, sensorial processes and hippocampal mossy fibre distribution in radial maze performance in mice. AB - Eight isogenic mice groups (6 inbred strains and 2 F1 hybrid generations) were tested on an eight-arm radial maze, using either a procedure of confinement (C) or a non-confinement (NC) to the central platform between trials, in order to control for the use of response strategies in learning. On the 6th day of training, the spatial surrounding was impoverished by removing the most salient visual cues of the room; thus allowing testing for the effective use of spatial cues during learning. Results showed that learning profiles and performance levels varied between strains within each procedure. These variations could correspond to a heterogeneity of the underlying perceptual processes involved in learning, since only some strains in each procedure were disturbed by the removal of spatial cues. Correlations between behavioural results and the distribution of mossy fibres in the hippocampus were analysed. The intercorrelation matrix revealed that correlations between the size of the infra-intrapyramidal synaptic field (IIP-MF) and some behavioural indices occurred only during the first trial on the maze, whatever the procedure. Learning performances on the 5th day of training did not correlate with any hippocampal measure. When the spatial surrounding was impoverished, on the 6th day of training, correlations with mossy fibres appeared only in the confinement procedure. PMID- 1622557 TI - Vestibular-neck interaction of human ocular counterroll. AB - Compensatory rolling of the eye about the line of sight (ocular counterroll, OCR) was studied in four normal human subjects during 10 min of lateral tilt (20 degrees to the left/right) of body, head and trunk. OCR was objectively measured at 1-min intervals by determining the rotation of a circular sample of iris pattern using a videocamera and digital image processing. Body and head tilt caused symmetrical OCR (range 2.4 to 9.5 degrees) to either side, whereas trunk tilt induced no significant change in torsional eye position. No adaptation in OCR was found during the time spent in tilted orientation in neither paradigm though unsystematic torsional fluctuation was a regular finding in all subjects. These findings are taken as evidence that only the non-adapting otolith system, as opposed to the proprioceptive system of the neck, contributes to the generation and maintenance of OCR. PMID- 1622558 TI - Hemispheric specialization for the control of copulation in the young chick and effects of 5 alpha-dihydrotestosterone and 17 beta-oestradiol. AB - After intramuscular treatment with either oestradiol (1 mg/day for 4 days) or 5 alpha-dihydrotestosterone (0.5 mg/day for 7 days) the copulatory behaviour of young male chicks was tested monocularly using removable eye-patches. From day 11 to 14 copulation scores were significantly elevated in chicks treated with oestradiol or 5 alpha-dihydrotestosterone (5 alpha-DHT) and tested either binocularly or monocularly using the left eye. There was no elevation of copulation when the treated chicks were tested monocularly using the right eye. Thus, in the binocular condition neural circuits receiving input from the left eye, and therefore likely to be on the right side of the brain, are specialized for the activation of copulation. This result confirms previous findings using chicks treated with testosterone. On day 14 the eye-patches were changed to the other eye. For chicks treated with oestradiol, those now tested using the left eye showed significantly higher levels of copulation than those now using the right. In other words, there was very little interocular transfer from left eye to right eye. However, after transferring the eye patches, the chicks treated with 5 alpha-DHT had high copulation scores irrespective of the eye used. This suggests that there may be an interaction between prior copulatory experience and 5 alpha-DHT levels which leads to either interocular transfer of copulation behaviour or equal access of both eyes to the brain regions which control copulation. PMID- 1622559 TI - C-fos protooncogene expression in rat brain after long-term training of two-way active avoidance reaction. AB - C-fos nuclear protooncogene encodes a regulatory protein (Fos), able to directly influence both expression of itself and other genes. It has been repeatedly shown that c-fos expression coincides with different forms of cell activation, probably being functionally involved in the coupling of extracellular ligands to long-term cellular responses. In this study it has been found that c-fos mRNA accumulation in rat brain, as measured by northern blotting coincides with increase of performance level of learned behavior of a two-way active avoidance task. We have previously reported (Nikolaev et al., Brain Res. Bull., in press) that a single training session of two-way active avoidance strongly induces c-fos mRNA accumulation but that after long-term training up to the asymptotic level of performance no c-fos expression was detectable. In this paper we show that c-fos still remains inducible even after long-term, asymptotic training to darkness as conditioned stimulus (CS), provided that a novel stimulus, wide band noise, which elevated performance level, was given together with darkness as compound CS. PMID- 1622560 TI - Behavioral factors in stress-induced immunomodulation. AB - Individual differences in the exploratory response to novelty were found to be related with the vulnerability to develop stress-induced immunological alterations. We studied the effect of exposure to inescapable shock on antibody formation against sheep red blood cells (SRBC) in rats selected according to their locomotor activity in a novel situation. Interestingly, antibody titers were only enhanced in shocked animals with the highest locomotor activity. These results emphasize the importance of taking into account individual differences for the study of the mechanisms involved in stress-induced immunomodulation, suggesting a behavioral procedure (novelty reactions) to deal with individual variability in the effects of stress on the immune system. PMID- 1622561 TI - The role of ozone in tracheal cell transformation. AB - This project examined the potential role of ozone as a respiratory carcinogen by characterizing its ability to induce or modulate the preneoplastic transformation of rat tracheal epithelial cells. The chemical reactivity of ozone and the types of damage it can cause suggest that it may have a role in environmental carcinogenesis. Previous reports have described an increase in the incidence and number of lung tumors per animal in strain A mice exposed to ozone. However, the role of ozone in the development of the tumors has not been clear. Ozone also has been reported to act alone and synergistically with ionizing radiation to induce changes related to neoplasia in primary hamster embryo cells and in the mouse C3H/10T1/2 cell line in culture. Few other studies have examined the direct cytotoxic or transforming effects of ozone after in vivo or in vitro exposure of cells, and no studies have been reported on the comparative effects of ozone on respiratory cells exposed in vivo or in vitro. The induction of early preneoplastic changes in populations of rat tracheal epithelial cells by carcinogens can be detected and quantified in vitro after exposures in vivo or in vitro of tracheal epithelial cells. This cell culture and transformation system was used to characterize the transforming potency of ozone. Tracheal epithelial cells were isolated from Fischer-344/N rats that had been exposed for six hours per day, five days per week for one, two, or four weeks to 0, 0.12, 0.5, or 1.0 parts per million (ppm)* ozone (sea-level equivalents). Cell populations were examined in culture for increases in the frequency of preneoplastic variants. Rats exposed to ozone did not exhibit an increase in the frequency of preneoplastic tracheal cells, although exposed tracheas did exhibit dose dependent morphological changes. Rat tracheal epithelial cells were given single, 40-minute in vitro exposures to concentrations of ozone that did not result in any detectable decrease in colony-forming efficiency (approximately 0.7 ppm) and to concentrations that resulted in approximately a 40% decrease (approximately 10 ppm). Exposed cultures were examined for increases in the frequency of preneoplastic variants. The results of these experiments, like those for the in vivo experiments described above, suggest that a single ozone exposure does not induce preneoplastic variants of rat tracheal epithelial cells. In contrast, cultures of rat tracheal cells exposed to 0.7 ppm ozone twice weekly for about five weeks exhibited approximately a twofold increase in the frequency of preneoplastic variants compared with control cultures.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1622562 TI - Basics of instrument sterilization. PMID- 1622563 TI - Disinfection in the dental office. PMID- 1622564 TI - Perilous root canals. PMID- 1622565 TI - Associateships: is there an end in sight. 2. PMID- 1622566 TI - Aseptic techniques for dental radiology. PMID- 1622567 TI - Dentists nationwide are finding a new way to help tobacco chewers practice safe snuff. PMID- 1622568 TI - An overview of dental office infection control. PMID- 1622569 TI - The W-5 dilemma of medical waste in the dental office: Who, What, When, Where and Why? PMID- 1622570 TI - Curved root canals: treating the most common endodontic complexity. PMID- 1622571 TI - Immediate-load implant quickens integration. PMID- 1622572 TI - Single tooth implants: difficult, yet overused. PMID- 1622573 TI - Enamel microabrasion in conjunction with carbamide peroxide bleaching. PMID- 1622574 TI - Patient-centered practices. PMID- 1622575 TI - Non productive staff meetings. The beginning of the end. PMID- 1622576 TI - Mandatory sterilization. Washington State forces dentists to autoclave handpieces after every use. PMID- 1622577 TI - High-copper casting alloys stir debate. PMID- 1622578 TI - Troubleshooting problem bonding cases. PMID- 1622579 TI - Power bleaching attempts to make a comeback. PMID- 1622580 TI - All-porcelain bonded restorations. PMID- 1622581 TI - An aesthetic alternative to crown and bridge. PMID- 1622582 TI - Aesthetics and function meet to "bridge" a molar gap. PMID- 1622583 TI - Snoring and obstructive sleep apnea. PMID- 1622585 TI - Guided tissue regeneration. PMID- 1622584 TI - Advancements usher in new era of periodontal care. PMID- 1622586 TI - Using the laser for implant maintenance. PMID- 1622587 TI - Choosing an ideal practice model. PMID- 1622588 TI - The team approach to cosmetic dentistry. PMID- 1622590 TI - Fear and AIDS: a deadly duo. PMID- 1622589 TI - Patient newsletters: why do they work for some practices and not for others. PMID- 1622591 TI - Custom mouthguards increase may increase player strength. PMID- 1622592 TI - The Wolfe nerve block: a modified high mandibular nerve block. PMID- 1622593 TI - The perfect material. The restorative maturation of resin inlays and onlays. PMID- 1622594 TI - Thermoplastic impression and temporary matrix materials. PMID- 1622595 TI - Eliminating sensitive composites. PMID- 1622596 TI - The keys to successful endodontics. PMID- 1622598 TI - Salaries--what is the normal limit? PMID- 1622597 TI - Pain control: dentistry's everyday challenge. PMID- 1622599 TI - Advances in the use of in vivo sensors. PMID- 1622600 TI - Biosensors based on the energy metabolism of living cells: the physical chemistry and cell biology of extracellular acidification. AB - The silicon microphysiometer is a biosensor-based instrument that detects changes in the physiological state of cultured living cells by monitoring the rate at which the cells excrete acidic products of metabolism. This paper discusses the chemical and biological factors that determine the performance and applications of such a system. Under typical culture conditions, extracellular acidification is dominated by the excretion of lactic and carbonic acids formed during the energy metabolism, using glucose and glutamine as carbon sources. The maintenance of transmembrane ionic gradients is an important use of energy, as is cell growth. The activation of cellular receptors usually causes transient or sustained increases in acidification rate. The energetic cost of generating second messengers is probably too small to account for either change, so events more distal to the receptor-activation process must be responsible. The opening of ion channels may cause the increases in some cases. In others, changes in intracellular pH and loose coupling between ATP hydrolysis and synthesis may be involved; models for these processes are presented. PMID- 1622602 TI - Covalent immobilization of avidin on glassy carbon electrodes as the basis for multivalent biosensors. AB - One of the most crucial steps for the successful construction of a biosensor is the appropriate and reproducible coupling of the biological part (e.g. enzyme, antibody) to the inorganic moiety of the device (e.g. electrode, microchip). In this paper three methods of immobilization of avidin to a glassy carbon electrode are described. Depending on the type of immobilization, avidin may lose its biological activity as determined by an enzyme immunoassay, using biotinylated reagents. If avidin is covalently bound to the glassy carbon electrode via the bridge molecule 4.4'-diaminodiphenylamine, the biological activity is retained. About 1.5 pmol of avidin can be bound to the electrode (3 mm in diameter), resulting in a nearly complete monolayer of protein. PMID- 1622601 TI - A novel microbial sensor using luminous bacteria. AB - A novel microbial sensor system that uses luminous bacteria was developed for the determination of both glucose and toxic compounds. The sensor system consisted of a membrane with luminous bacteria immobilized upon it and a photomultiplier. Measurements were based on the in vivo intensity of the light emitted by the bacteria, as this is affected by their environment. A linear relationship was observed between increased luminescence and concentrations of glucose between 0.05 mM and 0.55 mM. The relative standard deviation was 10% for 0.55 mM glucose (n = 10). Toxic compounds such as benzalkonium chloride, sodium dodecyl sulphate and chromium(VI) were also detected by measuring the decrease in luminescence in their presence. PMID- 1622603 TI - The electrical conductivity of phospholipid films as an iodine-sensing mechanism. AB - The d.c. electrical conductivity of dry phospholipid films is increased by some 8 11 orders of magnitude by the adsorption of iodine vapor. The conductivity of these films has been found to increase as a function of iodine 'vapor pressure' and the quantitative relationship between electrical conductivity and the adsorbed iodine has been determined. Films composed of phospholipids with unsaturated hydrocarbon chains are some three orders of magnitude more electrically conductive than are films of phospholipids containing saturated hydrocarbon chains. Optical spectroscopic measurements show the development of absorption bands centered near 294 nm and 365 nm, upon iodine adsorption. These bands are much more intense for unsaturated phospholipids than for saturated ones. X-ray diffraction studies show that exposure to iodine decreases the thickness of phospholipid bilayers containing unsaturated hydrocarbon chains but does not change the thickness of bilayers containing only saturated chains. The electrical response of the lipid films, upon exposure to iodine, suggests their possible use as iodine sensors. PMID- 1622604 TI - A new approach to the construction of potentiometric immunosensors. AB - An electrochemical immunosensor based on a new detection principle was developed. Laccase, which is able to catalyse the electroreduction of oxygen via the direct (mediatorless) mechanism was used as an enzyme label. The new detection method does not require the presence of an electrochemically active mediator, and the reaction substrates are atmospheric oxygen and electrons, the latter being taken by the active site of the enzyme label directly from the electrode. The formation of the complex between laccase-labelled antibody and antigen on the electrode surface resulted in a considerable (more than 300 mV) shift of the electrode potential. The rate of the increase of the electrode potential was inversely proportional to the concentration of the free antigen in the sample. The non specific adsorption of conjugate and other proteins on the electrode could be eliminated by using a polyethylenimine-based polymer on the electrode surface. Insulin was used as a model analyte. The sensitivity limit for this antigen was approximately 3 micrograms ml-1. PMID- 1622605 TI - Ellipsometric immunosensors for the determination of gamma-interferon and human serum albumin. AB - Ellipsometric immunosensors for gamma-interferon (gamma-INF) and human serum albumin (HSA) have been developed using gamma-INF and HSA covalently immobilized onto silicon plates. Detection is achieved by measuring the adsorption decrease (gamma, mg m-2) of monoclonal immunoglobulin G against gamma-INF or immunoglobulin fraction of rabbit blood serum against HSA when the concentration of antigen in mixtures of antibody-antigen is increased. The time of analysis is 50 min, the detection limit of gamma-INF is 15 nM (sensitivity -0.01 mg m-2 nM-1) and of HSA 2.5 nM (-0.06 mg m-2 nM-1). PMID- 1622606 TI - In-vitro binary release kinetics of sulphamethoxazole and trimethoprim microcapsules. AB - Sulphamethoxazole and trimethoprim are separately microencapsulated with polyacrylic resin: Eudragit RS 100. The data so obtained from the drug release have been analyzed according to the different existing kinetic models (1) Zero order (2) First order and (3) Higuchi Matrix Kinetics. It is observed that in both the cases of single component and binary release of sulphamethoxazole (SMZ) and trimethoprim (TMP), Higuchi mechanism predominates. Lastly, a comparative study is made between The Single and Binary release kinetics to correlate the diffusivity rate constant (KBL) and diffusion Coefficient (Da) which have been estimated according to Baker-Lonsdale method at pH 1.2. PMID- 1622607 TI - Validation of a HPLC method for the determination of bendazac and its main metabolite 5-hydroxybendazac in human plasma. AB - The purpose of this study was to validate an analytical method for the determination of bendazac and its main metabolite 5-hydroxybendazac in human plasma. The results obtained indicate that the method is reproducible, accurate, precise, sensitive and specific for the measurement of bendazac and 5 hydroxybendazac in the human plasma. Therefore it can be considered suitable for experimental purposes, routine application for drug monitoring and regulatory requirements. PMID- 1622608 TI - [Photostability of drugs]. PMID- 1622609 TI - [Transgenic animal systems in the expression of recombinant proteins of pharmaceutical interest]. PMID- 1622610 TI - Mechanism of physiologic and pathologic S3 gallop sounds. AB - Although the S3 gallop sound has long been used clinically as an indicator of left ventricular systolic dysfunction, the mechanism responsible for its production remains controversial. The same sound is often found in young healthy individuals, and whether a similar mechanism is responsible is also unknown. The relationship of the S3 gallop sound to the dynamics of left ventricular filling was compared in 18 healthy young triathletes and 15 older subjects with cardiac disease. Twenty healthy normal subjects without an S3 were included as controls. Phonocardiographic, two-dimensional echocardiographic, and Doppler echocardiographic analysis of left ventricular inflow were evaluated. The S3 in both groups always occurred close to peak early filling velocity (E), during early flow deceleration. Mean E deceleration rate was higher in the subjects with S3 (726 +/- 153 cm/sec2 in the triathletes and 819 +/- 274 cm/sec2 in those with cardiac disease) than in control subjects (563 +/- 131 cm/sec2, p less than 0.001 in both cases). Ten triathletes underwent examination both before and immediately after 30 degrees head-up tilt. E deceleration rate dropped significantly with head-up tilt (720 +/- 137 vs 590 +/- 174 cm/sec2, p less than 0.01), while concurrently the S3 disappeared or was diminished in amplitude. Similar changes were seen in subjects with cardiac disease. We conclude that both the "pathologic" and "physiologic" S3 are related to abnormally rapid deceleration of early diastolic left ventricular inflow. Although the presence of the S3 is not dependent on the state of left ventricular systolic function, diastolic filling is characterized by a predominance of early inflow with a rapid flow deceleration rate. PMID- 1622611 TI - Doppler-derived aortic flow measurements during and after heavy isometric exercise in healthy men versus men with myocardial infarction. AB - Doppler echocardiography is a useful noninvasive determination of left ventricular function during dynamic exercise. Scarce data are available for the use of this technique during heavy isometric exercise. Therefore, Doppler-derived aortic flow indexes were assessed during and after 50% maximal upper-body isometric exercise in 25 healthy men (aged 47 +/- 6 years) and compared with those of 22 men (aged 48 +/- 9 years) who had suffered myocardial infarction. The heart rate increased (p = 0.01) in each of the groups from a mean of 68 +/- 12 at rest to 84 +/- 11 during isometric exercise. At rest, systolic blood pressure was higher (p = 0.05) in the patients with coronary artery disease. During exercise, the patients with cardiac disease, compared with the healthy volunteers, demonstrated a lesser reduction in flow velocity integral, stroke volume, and cardiac indexes (p = 0.001). Immediately on recovery, the patients with cardiac disease, compared with the healthy group, showed significantly greater (p = 0.001) increase in stroke volume and cardiac indexes. At 3 minute's recovery, the stroke volume index continued to increase in the patients with cardiac disease, while the healthy group showed a decrease to below its resting value. Although 50% of maximal upper-body isometric exercise caused similar heart rate and systolic blood pressure responses in healthy patients and patients with cardiac disease, there were significant group differences in Doppler-derived left ventricular systolic function indexes, which were greatest on immediate and 3 minute's recovery. The results suggest that this novel isometric test may be useful in clinical testing. PMID- 1622612 TI - Exercise Doppler echocardiography as an aid to clinical decision making in mitral valve disease. AB - The timing of valve replacement in patients with mitral valve disease, severe resting pulmonary hypertension, and severe symptoms is usually straightforward. However, this may not be true for patients with mild to moderate resting pulmonary pressures and symptoms that are difficult to evaluate. The measurement of hemodynamic parameters with exercise has been useful during cardiac catheterization. The purpose of this study was to evaluate the hemodynamic significance of dyspnea provoked by exercise in patients with mitral valve disease using exercise Doppler echocardiography. Nineteen tests were done in 17 patients (two patients had repeat studies 1 year after the first test). Dyspnea developed in patients during exercise in 11 tests, and the others were limited by fatigue (and angina in one patient). There was a significantly greater increment in pulmonary artery systolic pressure during exercise in the patients who developed dyspnea (24 mm Hg) than in those who did not (15 mm Hg, p = 0.04). The two groups exercised to approximately the same heart rate and blood pressure, but the dyspneic patients had a significantly shorter exercise capacity (p = 0.04). Furthermore, clinical decision making was affected by the test results in 84% (only three tests did not affect patient management) and included a decision to proceed to invasive testing and surgery in seven patients, and a decision to treat the patient medically in nine. In conclusion, exercise Doppler echocardiography is a useful adjunct in the diagnosis and treatment of patients with mitral valve disease and an aid to clinical decision making. PMID- 1622613 TI - Diagnosis of coronary artery disease using exercise echocardiography and positron emission tomography: comparison and analysis of discrepant results. AB - Both exercise echocardiography and rubidium-82 positron emission tomography are used in the detection and characterization of coronary artery disease. This study compared results of both in 74 patients with known coronary anatomy, by use of exercise echocardiography before and after treadmill exercise and positron emission tomography with intravenous dipyridamole-handgrip stress. Significant (greater than 50%) coronary stenoses were present in 70 patients; exercise echocardiography and positron emission tomography each identified 63 patients (sensitivity 90%). Significant stenoses without previous myocardial infarction were present in 34 patients; 29 (85%) were identified by exercise echocardiography and 28 by positron emission tomography (82%, p = NS). Four patients had no significant coronary disease, and were all identified as normal by both methods. Segments were classified as either normal or showing stress or resting abnormalities, and the diagnoses were compared in the territories of the three major coronary arteries. Results were concordant with respect to the presence or absence of coronary disease in 185 of 222 territories (83%). The remaining 37 regions had abnormalities by exercise echocardiography or positron emission tomography but not both. Stress defects were identified by only one of the tests in 24 areas (in 12 [50%], angiographic findings correlated with positron emission tomography). Resting defects were diagnosed by only one modality in 13 regions (angiographic findings correlated with the results of positron emission tomography in 9 [69%] of these). Both exercise echocardiography and positron emission tomography are sensitive for the identification of coronary artery disease, although on a regional basis, positron emission tomography appears to be more specific for the diagnosis of resting perfusion defects. PMID- 1622614 TI - Value of pulmonary venous flow characteristics in the assessment of severity of native mitral valve regurgitation: an angiographic correlated study. AB - To evaluate the relation between left ventricular angiography and pulmonary venous flow velocity in native mitral valve regurgitation, 28 patients with sinus rhythm and valvular and/or coronary artery disease underwent transesophageal echocardiography within 24 hours after cardiac catheterization. Group I consisted of 17 patients, seven patients without (grade 0) and 10 patients with angiographically mild to moderate mitral regurgitation (grades 1 and 2). Group II consisted of 11 patients with angiographically severe mitral regurgitation (grades 3 and 4). Mitral regurgitation by transesophageal echocardiography was evaluated by measuring the regurgitant jet sizes and color-guided pulsed Doppler pulmonary venous flow velocities. Multivariate analysis revealed that the most powerful predictor (p less than 0.001) of angiographically severe (grades 3 and 4) mitral regurgitation was reversed systolic flow into the left upper pulmonary vein (sensitivity 82%, specificity 100%, positive predictive value 100%). If this variable was excluded from analysis, jet area and jet length (p less than 0.001) were the next best predictors for angiographically severe mitral regurgitation. Mean values of systolic peak pulmonary venous flow velocities were significantly lower in patients from group II, 13.0 +/- 11.1 cm/s versus 43.4 +/- 20.6 cm/s (group I) with p less than 0.005. This finding was also true for systolic time velocity integral, 1.3 +/- 1.3 cm (group II) versus 7.8 +/- 5.3 cm (group I) with p less than 0.005.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1622615 TI - Attachment of a balloon to a transesophageal echocardiographic transducer for improvement of contact with the esophageal wall. AB - We attached a water-inflated balloon to a transesophageal probe to improve contact of the transducer with the esophageal wall and used it in 26 patients with congenital heart disease. Balloons for this study were made for use in hemostatic therapy for esophageal varix. The contact of the transducer with the esophageal wall was successfully improved in all the patients, which resulted in improvement of the signal-to-noise ratio in both two-dimensional and Doppler echocardiography. The appropriate filling volume of water was within 5 ml to avoid compression of the left pulmonary vein and to avoid the artifact of multiple reflection. PMID- 1622616 TI - Cardiovascular changes in pregnancy evaluated by two-dimensional and Doppler echocardiography. AB - During pregnancy significant cardiovascular changes occur. To study these anatomic and physiologic changes we performed two-dimensional and Doppler echocardiography in 28 women during the third trimester (34.4 +/- 1.9 weeks) of pregnancy and then again after delivery (7.8 +/- 2.2 weeks). Fourteen nonpregnant age- and sex-matched subjects served as controls. Left ventricular diastolic and systolic dimensions were similar among pregnant, postpartum, and control subjects. Left atrial area as determined by two-dimensional echocardiography was significantly larger during pregnancy (16.7 +/- 4.0 cm2) compared with measurements postpartum (13.8 +/- 3.1 cm2) and with controls (15.5 +/- 3.5 cm2) (p less than 0.01). Doppler study showed that the ratio of early diastolic flow velocity to late diastolic flow velocity (E/A max) and E/A integral were lower among pregnant subjects (1.3 +/- 0.3, 2.0 +/- 0.5) compared with postpartum subjects (1.6 +/- 0.4, 2.5 +/- 1.5) and controls (1.9 +/- 0.5, 3.0 +/- 0.8) (p less than 0.05). Heart rate was higher among pregnant subjects (84 +/- 10 beats/min) compared with postpartum subjects (70 +/- 16) and controls (69 +/- 13) (p less than 0.05). In summary, in pregnant subjects during late third trimester left ventricular chamber dimensions were similar to these postpartum measurements in control subjects; however, the left atrium is dilated during pregnancy. Although there are significant alterations in Doppler-derived left ventricular diastolic parameters during the third trimester, increased heart rate and a dilated left atrium may explain these findings. PMID- 1622617 TI - Patent foramen ovale: a nonfunctional embryological remnant or a potential cause of significant pathology? AB - A patent foramen ovale (PFO) is an embryological remnant found in 27% of adults. It is a potential right-to-left intracardiac shunt. Shunting may be the result of reversal in the interatrial pressure gradient or abnormal streaming of blood in the right atrium. The pathologic consequences of right-to-left shunting include hypoxemia and paradoxical embolism. PFO may exacerbate preexisting hypoxemia or be its primary cause. Paradoxical embolism through a PFO is well documented. Its role in cryptogenic stroke remains controversial. A PFO may be detected by both invasive and noninvasive techniques. Contrast transesophageal echocardiography with provocative maneuvers is the diagnostic method of choice allowing visualization of the shunt. Patients with cryptogenic stroke should be screened for a PFO. If detected, noninvasive studies for deep vein thrombosis are recommended. Treatment must be tailored to the presentation. Surgical or transcatheter closure is recommended for hypoxemia. Prevention of venous embolism (air or thrombus) with or without closure of the PFO is recommended for paradoxical embolism. PMID- 1622618 TI - Embolization of a left atrial ball thrombus during transesophageal echocardiography. AB - We report a case of systemic embolization of a left atrial ball thrombus during transesophageal echocardiography (TEE). A 49-year-old man with rheumatic mitral stenosis and atrial fibrillation underwent TEE to evaluate a transient cerebral ischemic attack. TEE demonstrated a free-floating left atrial thrombus. Disappearance of the thrombus during the study occurred after tachycardia and was associated with acute hemiplegic stroke and an absent radial pulse. The possible mechanism of embolization and the implications for the selection and management of patients undergoing TEE are discussed. PMID- 1622619 TI - Free vortex ring formation in the left atrium originating in the left auricle. AB - An 80-year-old woman was evaluated by transesophageal echocardiography after coronary artery bypass surgery and subsequent cardioembolic stroke. In addition to spontaneous echo contrast demonstrating a counterclockwise rotating blood flow pattern, we observed free vortex ring formation in the left atrium, originating in the left auricle. To our knowledge, this is the first reported case of abnormal free vortex ring type flow pattern in the left atrium. PMID- 1622620 TI - Coronary artery fistula: diagnosis by biplane transesophageal echocardiography. AB - A 56-year-old man underwent coronary angiography during evaluation of severe mitral regurgitation. A right coronary artery fistula was incidentally discovered but its site of termination was uncertain. Transthoracic echocardiography also did not reveal the location of its drainage. The correct diagnosis of a right coronary artery to left atrial fistula was made using biplane transesophageal echocardiography. This case demonstrates the utility of biplane transesophageal echocardiography in the diagnosis of the origin and termination of congenital coronary artery anomalies. PMID- 1622621 TI - Cardiac assessment in Turner's syndrome: a case for the inclusion of coronary angiography. AB - This case reveals a 25-year-old woman presenting with a supraventricular tachycardia who was found to have Turner's syndrome. Color flow Doppler echocardiography revealed diastolic jets, which cardiac arteriography confirmed as coronary artery-pulmonary artery fistulas. PMID- 1622622 TI - Prophylaxis or no prophylaxis before transesophageal echocardiography? PMID- 1622624 TI - Extraordinary spring meeting of the Spanish Society of Neurology and the 1st joint meeting of the Spanish Society of Neurology and the Neurological Section of the Austrian Society of Neurologists and Psychiatrists. Platja d'Aro, 3-6 June 1992. PMID- 1622623 TI - Critical appraisal of transesophageal echocardiography: limitations, pitfalls, and complications. AB - Because transesophageal echocardiography is invasive, it has the potential for serious complications. Limitations occur because of the restricted transducer mobility within transducers for special situations. Pitfalls (potential erroneous diagnoses resulting from misinterpretation of normal and abnormal anatomy) are prevalent with this new technology. This report critically reviews transesophageal echocardiography and discusses and illustrates commonly encountered limitations, pitfalls, and complications. PMID- 1622625 TI - The biology of breast tumor progression. Acquisition of hormone independence and resistance to cytotoxic drugs. AB - Many breast tumors appear to follow a predictable clinical pattern, being initially responsive to endocrine therapy and to cytotoxic chemotherapy but ultimately exhibiting a phenotype resistant to both modalities. Using the MCF-7 human breast cancer cell line as an example of an 'early' phenotype (estrogen and progesterone receptor positive, steroid responsive, low metastatic potential), we have isolated and characterized a series of hormone-independent but hormone responsive variants (MIII and MCF7/LCC1). However, these variants remain responsive to both antiestrogens and cytotoxic drugs (methotrexate and colchicine). MIII and MCF7/LCC1 cells appear to mimic some of the critical aspects of the early progression to a more aggressive phenotype. An examination of the phenotype of these cells suggests that some hormone-independent breast cancer cells are derived from hormone-dependent parental cells. The development of a hormone-independent phenotype can arise independently of acquisition of a cytotoxic drug resistant phenotype. PMID- 1622626 TI - Biological and clinical significance of cathepsin D in breast cancer. AB - Cathepsin D, an aspartyl protease of lysosomes, is overproduced and hypersecreted by breast cancer cells. The prognostic value of its immunoassay in breast cancer cytosol is reviewed from the first retrospective clinical studies available, which show a strong correlation between high concentrations of cathepsin D in the cytosol of primary tumor and further occurrence of metastasis. This new prognostic factor is induced by estrogen in hormone dependent breast cancer but expressed at a high level in hormone independent breast cancer and appears to be independent of other more classical factors. Its value in node negative patients varies according to the studies. In nude mice, transfection of cathepsin D cDNA into tumor cells increases their metastatic potential, suggesting that overexpression of this protease may be one of the factors responsible for metastasis in human breast cancer. The mechanism by which this protease might facilitate metastasis in vivo is still unknown, even though cathepsin D has the potential to initiate a proteolytic cascade, to degrade extracellular matrix and to liberate FGFs like growth factors from the matrix. These studies should stimulate the search for new therapeutical agents in order to inhibit cathepsin D action. PMID- 1622627 TI - Effect of estrogen and antiestrogens on cell proliferation and synthesis of secreted proteins in the human breast cancer cell line MCF-7 and a tamoxifen resistant variant subline, AL-1. AB - The human breast cancer cell line MCF-7 contains estrogen receptors and responds to estrogens with an increase in growth rate and to antiestrogens with a decrease in growth rate. Estrogen stimulation of cell proliferation is concomitant with an increase in the synthesis and secretion of three proteins with mol. wt 52 kDa, 61 kDa and 66 kDa and a decrease in the synthesis and secretion of a 42 kDa protein. The antiestrogen ICI 164,384 has a complete estrogen antagonistic effect on the synthesis of these secreted proteins, whereas the antiestrogen tamoxifen has an agonistic effect on the synthesis and secretion of the 52 kDa protein. We believe that the above mentioned estrogen regulated secreted proteins are either directly or indirectly involved in control of cell proliferation, and the less pronounced inhibitory effect of tamoxifen on cell proliferation compared to ICI 164,384 may be due to agonistic effects of tamoxifen. A tamoxifen resistant variant of the MCF-7 cell line, the AL-1 subline, can be growth inhibited by ICI 164,384, although a higher concentration is needed to inhibit the AL-1 cells compared to the parent MCF-7 cells. Tamoxifen has no effect on secreted proteins from the AL 1 cells, whereas ICI 164,384 has a complete estrogen antagonistic effect on secreted proteins, indicating that the mechanisms by which estrogens and antiestrogens influence cell proliferation may be via up and down regulation of secreted proteins with growth regulatory functions. PMID- 1622628 TI - Analysis of hormone receptors and proliferation fraction in fine-needle aspirates from primary breast carcinomas during chemotherapy or tamoxifen treatment. AB - Twelve postmenopausal women (54-93 years) with primary breast carcinoma were treated with tamoxifen due to infirmity or refusal to undergo surgery. Seven premenopausal patients (32-50 years) were given preoperative chemotherapy because of large tumors or inflammatory carcinoma. Fine-needle aspiration biopsy was used to procure tumor cells for diagnosis, hormone receptor determination and analysis of proliferation fraction. Aspirations were repeated every 3 months in the tamoxifen group and each month in patients receiving chemotherapy. Two patients who responded to tamoxifen had tumors with more than 75% estrogen receptor positive cells. A decreased proliferation fraction was observed in two tumors responding to tamoxifen. Eight patients, all with estrogen receptor positive tumors, had stable disease. Progressive disease was observed in two patients with less than 25% receptor positive cells. In these tumors the percentage of proliferating cells remained high during therapy. Objective response was recorded for six patients treated with chemotherapy. The clinical response was reflected in a decreased proliferation fraction. No correlation was observed between response and percentage of proliferating cells in the untreated tumor. The results suggest that analysis of tumor cell characteristics such as hormone receptor content and proliferation fraction can be used to predict and monitor response to endocrine treatment and chemotherapy in breast carcinomas. PMID- 1622629 TI - Role of genetic factors in breast cancer susceptibility. AB - Hereditary breast cancer is common and accounts for approximately 10-14% of all breast cancers. Knowledge of a family history of breast cancer may significantly influence diagnosis and therapy. Genetic heterogeneity has been demonstrated in familial breast cancer. Recently inherited mutations in the tumor suppressor gene p53, have been shown to be the underlying defect in the Li-Fraumeni syndrome. We have shown that defects in this gene also play a role in the predisposition to other familial breast cancers. The gene responsible for early onset familial breast and ovary cancer has recently been mapped to chromosome 17q21. For most of the sporadic breast cancers a multifactorial model, including variable genetic and environmental factors, has been considered. Two genetic risk factors which may predispose for a considerable portion of breast cancers are the gene causing ataxia telangiectasia (AT) and the gene that gives rise to proliferative breast disease (PBD). Identification of distinct genes enhancing the risk of breast cancer will give us the opportunity to identify high risk individuals. Such individuals may benefit from periodic examination affording the possibility of early diagnosis and treatment. PMID- 1622630 TI - Flow cytometric DNA index and S-phase fraction in breast cancer in relation to other prognostic variables and to clinical outcome. AB - One frequently used classification of flow cytometric DNA ploidy status (diploid versus nondiploid) was compared with a division into seven ploidy classes based on DNA index (DI) and number of cell populations (hypodiploid, diploid, near hyperdiploid, hyperdiploid, tetraploid, hypertetraploid, and multiploid). The latter ploidy classification showed a better correlation with prognosis and other prognostic factors (i.e., lymph node involvement, estrogen and progesterone receptor status, and S-phase fraction). The improvement in correlation was mainly due to the identification of near-hyperdiploid cases (DI 1.00-1.14) which could be combined with the diploid cases to form a group with favourable prognosis. In contrast to cases with a small increase in DNA content (near-hyperdiploid), those with a small decrease of DNA content (hypodiploid) manifested a more aggressive disease. In multivariate analysis, S-phase fraction (SPF) was a more important prognostic factor than both the improved or the conventional ploidy classification. PMID- 1622632 TI - Oral contraceptives and breast cancer. A review with some comments on mathematical models. AB - The relationship between oral contraceptive use and breast cancer is discussed on the basis of information given in review articles, meta-analyses and editorials emphasizing methodological problems related to bias and confounding. Over the last few years a shift in opinion has taken place. Most reviewers now consider that long-term use of oral contraceptives is associated with an increased risk of premenopausal breast cancer and no effect among postmenopausal breast cancer. This result is compatible with an additive effect (in rate measure scale) of oral contraceptive use on breast cancer risk. PMID- 1622631 TI - The prevention of breast cancer through reduced ovarian steroid exposure. AB - Analysis of epidemiologic data on cancers of the breast, ovary and endometrium; the effects of endogenous hormones on cell proliferation; and current carcinogenesis concepts, suggest that hormonal contraceptives can be developed that will reduce lifetime risk of all 3 cancers. The 'unopposed-estrogen hypothesis' accounts for endometrial cancer risk factors. Ovarian cancer risk is closely related to the total frequency of ovulation. The risk of breast cancer can be explained by an 'estrogen-plus-progestogen hypothesis'. On the basis of this analysis an hormonal contraceptive regimen has been developed consisting of a gonadotropin-releasing hormone agonist (GnRHA) plus continuous low-dose add back estrogen and a short course of progestogen every fourth month. The total dose of add-back estrogen is estimated to be approximately 38% that in present day low-dose combination-type oral contraceptives (COCs). The total dose of progestogen is approximately 15% that in COCs. This regimen prevents ovulation and should thus reduce ovarian cancer risk. It also reduces the exposure of the endometrium to unopposed estrogen, and the exposure of the breast to estrogen plus-progestogen. It is estimated that use of such a regimen for 10 years will only reduce lifetime risk of endometrial cancer by one-sixth, but lifetime risk of ovarian cancer is estimated to be reduced by two-thirds, and lifetime risk of breast cancer is estimated to be reduced by one-half. PMID- 1622633 TI - Reproductive factors in breast cancer epidemiology. AB - There is abundant epidemiologic evidence showing that early menarche, late menopause, low parity and late age at first birth are related to increased risk of breast cancer. However, in younger age groups, uniparous women seem to be at higher risk than nulliparous, and the effect of later pregnancies is less clear in this group. Intervals between pregnancies may modify the general protective effect. Some studies have indicated an adverse effect of late age at pregnancies after the first. Further studies are necessary to determine if the general protective effect of pregnancies after the first is preceded by a transient increase in breast cancer risk. No clear association has been established with number of abortions. Results from two large prospective studies suggest that breast feeding is not strongly related to risk of breast cancer among Western populations. PMID- 1622634 TI - Prospective study of height, body mass index and risk of breast cancer. AB - The associations of breast cancer risk with height and body mass index have been examined in 291 cases of breast cancer that occurred among 25,967 Norwegian women during a mean follow-up of approximately 14 years (range 12-16 years). There was an overall increased risk of breast cancer with increasing body height, and the relative risk of women in the fourth quartile of height (mean = 170 cm) was 1.43 (95% confidence limits, 1.18-1.73) compared to women in the lowest quartile (mean = 155 cm), after adjusting for age, parity, age at first birth, and county of residence. Simultaneously, there was an overall inverse relation between body mass index (BMI) and breast cancer risk, which, however, was confined to women 50 years or younger. After adjustment for age, parity, age at first birth, and county of residence, the relative risk of women (less than or equal to 50 years) in the highest quartile of BMI (mean Quetelet = 30) was 0.63 (95% confidence limits, 0.48-0.82), compared to women in the lowest (mean Quetelet = 21). We propose that the lower breast cancer risk in shorter women may reflect caloric restriction during the pre- and peripubertal period, which may affect hyperplastic growth, and lead to a reduced number of breast tissue cells. The negative association with BMI may be related to a lower rate of cell division of breast tissue among obese premenopausal women. PMID- 1622635 TI - Risk of breast cancer among female teachers of physical education and languages. AB - A retrospective follow-up study on 924 physical education (PE) and 3,239 language (L) teachers was performed to study whether life-long high physical activity affects the risk of breast cancer. The Finnish Cancer Registry found 128 malignant breast cancers among these women in a follow-up during 1967-1987. The standardized incidence ratio (SIR) for all PE teachers was 1.28 (n.s.) and for L teachers 1.59 (p less than 0.001). Before the menopause (below age 50) SIR for PE teachers was 0.93 (n.s.) and for L teachers 1.51 (p less than 0.05). These results suggest that before menopause the risk of breast cancer in physically active PE is smaller than in the less active L. A Poisson regression analysis, taking into account the reproductive factors together with age and observation period, did not show any significant difference between PE and L teachers, probably due to the relatively small number of cases (n = 22) in the PE teacher group. PMID- 1622636 TI - Indications for cytostatic therapy in metastatic breast cancer. AB - Generalized breast cancer is always incurable. The heterogeneity of this disease is reflected by wide variation in treatment response and survival duration. No well-defined factors have been found which can distinguish the patients most likely to benefit from chemotherapy. No superior drug combination or schedule has been convincingly established, and basic facts on quality of life issues are still lacking. The most important treatment goal is to provide meaningful palliation for the individual patient. Indications for chemotherapy are life threatening disease, distant metastases in receptor-negative disease, and clinically hormone resistant disease. In future trials the importance of potentially relevant biological factors for treatment should be evaluated, and such analyses should, at least partly, replace the presently conducted phase II and phase III studies. PMID- 1622637 TI - Cytotoxic treatment of metastatic breast cancer. Which drugs and drug combinations to use? AB - Although the optimal efficacy of cytotoxic therapy plateaued in the 1970s, no consensus yet exists regarding which cytotoxic combination to offer as first-line therapy for metastatic breast cancer. Comparison of a combination of CAF/CEF with other cytotoxic combinations reveals that an anthracycline-containing regimen not only increases response rate, but also improves time to progression and survival. Regarding appropriate duration of cytotoxic therapy, randomized trials indicate that therapy in excess of 6 months is beneficial. Although the main objective of cytotoxic therapy in patients with metastatic disease is to palliate symptoms at the least toxic cost, the finding that adjuvant cytotoxic therapy improves survival provides a clinical and ethical rational for continued research into new drugs and combinations in the hope that new strategies can be employed not only against metastatic breast cancer but may be applied with benefit also in the adjuvant situation. PMID- 1622638 TI - Site-specific effect of chemotherapy in patients with breast cancer. AB - The efficacy of cytotoxic therapy in different anatomical sites can be studied by analyzing the anatomical distribution of recurrences following adjuvant therapy or the rate of response according to site of metastasis. Cumulated data from 7 adjuvant studies showed that the relative reduction in the rate of recurrence was 37% for local and regional recurrences versus 25% for distant metastases. There are only sparse and inconclusive data concerning the anatomical pattern of recurrence according to type of adjuvant chemotherapy. Thus, the majority of trials have not demonstrated significant differences in distribution of metastases in patients receiving different types of adjuvant systemic therapy. The available data on the rate of response in relation to metastatic site showed higher response rates in soft tissue metastases (55%), compared to visceral and bone metastases (40%). Cumulated data from 12 trials showed no differences in response rates between different soft tissue lesions (skin, subcutaneous tissue, lymph nodes, breast), or between metastases demonstrated by paraclinical tests (lung, liver, bone). However, there was a tendency for soft tissue lesions to have a higher response rate (55-60%) than visceral and bone metastases (31-44%). The reason for the observed differences is unknown. At the time of diagnosis soft tissue lesions may be smaller (with better blood supply) than visceral lesions. This might increase the likelihood of response, since experimental data show that the response rate is inversely correlated with tumour burden and tumour size. Another explanation is based on the hypothesis of site-specific clonal selection of tumour cells, which differ with respect to sensitivity to cytotoxic agents. However, the observed differences can also be ascribed to methodological errors or differences in assessing response of tumours at specific sites. Thus, the false positive response rate in soft tissue lesions, evaluated by physical examination, is approximately 20% compared with less than 10% in lung lesions evaluated by x-rays. PMID- 1622639 TI - FEC (5-fluorouracil-epirubicin-cyclophosphamide) monthly versus FEC weekly in metastatic breast cancer. First results of a randomized trial. AB - Patients (n = 174) with metastatic breast cancer previously untreated with anthracycline cytotoxic agents were randomized into two groups: Group 1 received FEC (5-fluorouracil 500 mg/m2, epirubicin 60 mg/m2 and cyclophosphamide 500 mg/m2) once every fourth week and group 2 received the treatment once weekly in the same monthly dosage. Treatment was recommended to continue until disease progression or to a cumulative epirubicin dose of 1,000 mg/m2, but could be discontinued at any time at the patient's request or at the treating physician's judgement. An interim analysis was made when 131 patients were evaluable for response, and 128 patients for toxicity. Hematological toxicity was significantly more severe in the monthly group, as was nausea and vomiting. Of the monthly treated patients 76% had total alopecia compared to 14% in the weekly group. There were no statistically significant differences in the occurrence of mucositis. Monthly FEC gave significantly higher response rate than weekly treatment (52 vs 34%, p = 0.01). Time to progression was significantly (p = 0.004) longer with monthly FEC. Patients in the monthly treated group lived significantly (p = 0.02) longer than patients in the weekly group. These results indicate that both toxicity and efficacy of epirubicin-containing combination therapy in breast cancer is dependent on the treatment schedule, not merely on dosage. Both efficacy and toxicity increased when the treatment was given once monthly compared to the weekly schedule. PMID- 1622640 TI - Late effects of radiotherapy in the treatment of breast cancer. AB - Late effects after radiotherapy for breast cancer include radiation induced malignancy and changes in irradiated tissues leading to e.g. edema of the arm, decreased mobility of the shoulder joint, brachial plexus neuropathy, pulmonary fibrosis, telangiectasia or atrophic ulceration of the skin. While radiation induced malignancy depends on the volume of tissue irradiated and the total dose, other late effects are also fractionation dependent. Several reports have shown increased rates of such late effects after changes of the fractionation schedule which should be isoeffective according to the mathematical models commonly used to predict early effects. Although knowledge of the relation between total dose, number of fractions and radiation effects in late responding tissues has increased, extrapolations from the models should be used cautiously. The dose response curve seems to be steeper for late effects than for tumour control. The possibility of late effects should be included in the decision as to when and how to treat breast cancer with radiotherapy. PMID- 1622641 TI - Long-term effects of adjuvant chemotherapy in breast cancer. AB - Late effects of adjuvant chemotherapy (ACT) may include second malignant neoplasms (SMN), cardiotoxicity and ovarian suppression. Effects on the biology of residual tumour may be important in protocol design. Studies of SMN need large and reliable data sets. The leukaemia risk with current ACT is likely to be less than a five-fold increase. Leukaemia is predominantly a result of alkylating agents and peaks before 10 years. Solid SMN result also from radiotherapy and this risk continues after 10 years. Cardiotoxicity can be caused by anthracyclines but should not be a problem with current ACT regimens. It can be reduced by careful monitoring and by the cardioprotector ICRF-187. Amenorrhoea is a crude marker of ovarian suppression which may explain conflicting data on its relationship to outcome after ACT. Ovarian suppression following ACT is more likely and more permanent in older premenopausal women, but only explains a part of the ACT effects on outcome. Effects of early ACT on residual tumour are important for planning retreatments and combined modality protocols. PMID- 1622642 TI - Results of the Cancer Research Campaign Adjuvant Trial for Perioperative Cyclophosphamide and Long-Term Tamoxifen in Early Breast Cancer reported at the tenth year of follow-up. Cancer Research Campaign Breast Cancer Trials Group. AB - Over 2,000 patients with early breast cancer were recruited into a trial between 1980 and 1985. This trial was of a factorial 2 x 2 design to investigate the benefits of a short course of perioperative cyclophosphamide or tamoxifen 20 mg daily for 2 years. At the tenth year of follow-up no significant benefit is noted for perioperative cyclophosphamide, however the main effect analysis for adjuvant tamoxifen demonstrates a significant improvement in disease-free survival which increases with time during the follow-up period. These results are in keeping with the World Overview of Trials of Adjuvant Tamoxifen. However, this study is unique, having a large number of node negative patients and over 500 premenopausal women in a comparison of tamoxifen and control. The relative risk reductions for the node negative patients for disease-free survival are greater than for the node positive patients. This might suggest that the absolute benefit for adjuvant tamoxifen is similar in both groups of patients, bearing in mind the increased risk of relapse with the node positive patients. No trend for interaction emerges according to age or menopausal status suggesting an identical benefit for premenopausal women. Of particular interest is the development of contralateral breast cancer. The initial overall effect which emerged at the third year of follow-up ceases to be apparent. However, subgroup analysis according to menopausal status suggests a trend for interaction with a reduction in the risk of contralateral breast cancer in the postmenopausal women and an increase in the risk of contralateral breast cancer in premenopausal women. Plausible mechanisms exist to explain this difference in outcome and these data need to be checked against other large trials of adjuvant tamoxifen at a time when we are considering the chemoprophylaxis of breast cancer in high risk premenopausal women. PMID- 1622643 TI - Carcinogenic effects of adjuvant tamoxifen treatment and radiotherapy for early breast cancer. AB - The occurrence of new primary tumours among postmenopausal patients with primary breast cancer subsequent to adjuvant treatment in Denmark was assessed by linkage to the cancer registry. Following primary surgery, patients in low risk of recurrence (n = 1,828) received no further treatment while patients in high risk randomly received either adjuvant radiotherapy alone (n = 846) or radiotherapy + tamoxifen 30 mg daily for 48 weeks (n = 864). With a median follow-up of 8 years, the incidence of tumours in the contralateral breast was similar among tamoxifen treated, and non-treated high-risk patients even after adjusting for tumours arising within the first year. The standardized incidence ratio for endometrial cancer was 1.9 (95% confidence interval 0.8-3.9) among tamoxifen treated, the cumulative incidence 1% compared to 0.3% among non-treated patients (p = 0.11). The cumulative risk of non-lymphocytic leukaemia was 0.9% and 0.1% among irradiated and non-irradiated patients respectively (p = 0.4). Prolonged follow up of tamoxifen-treated patients with regard to new tumours is recommended. PMID- 1622644 TI - Randomized trial of adjuvant tamoxifen in node negative postmenopausal breast cancer. Stockholm Breast Cancer Study Group. AB - The paper presents long-term results of a randomized trial of adjuvant tamoxifen (40 mg daily for 2 or 5 years) versus surgery alone including 1,347 postmenopausal patients with histologically negative axillary nodes and a tumour diameter less than or equal to 30 mm. Data on the estrogen receptor status of the primary tumour were available in 1,136 patients (84%). At a median follow-up of 7 years (range 1.7-13.0 years) there was a significant prolongation of the recurrence-free survival among those allocated to tamoxifen (p less than 0.01), significantly fewer deaths due to breast cancer (p = 0.02) and a trend towards improved overall survival (p = 0.11). The treatment benefit was restricted to patients with ER-positive tumours. There was no significant reduction of breast cancer recurrences in the tamoxifen group among patients whose tumours were classified as ER-negative. The results support and extend previous studies in showing a long-term benefit of tamoxifen in postmenopausal breast cancer patients with node-negative, estrogen receptor positive disease. PMID- 1622645 TI - Long-term effects of adjuvant tamoxifen and/or radiotherapy. The South Sweden Breast Cancer Trial. AB - In a multicenter trial of adjuvant therapy in stage II breast cancer, 719 postmenopausal patients were randomized to one of three treatment regimens: radiotherapy only or in combination with adjuvant tamoxifen for one year, or adjuvant tamoxifen without radiotherapy. At twelve years of follow-up (median 9 years), no statistically significant differences in survival or recurrence-free survival were observed. However, the rate of loco-regional recurrency was lower among patients treated with both radiotherapy and tamoxifen. The rate of bilateral breast cancer was reduced in tamoxifen-treated patients whereas the rate of new primary malignancies other than breast cancer was somewhat higher in tamoxifen-treated patients. Adjuvant therapy in breast cancer may influence not only breast cancer recurrences and mortality but also later disease patterns and cause-specific mortality. PMID- 1622646 TI - Lymphoma incidence in a Swedish county during 1969-1987. AB - The incidence of lymphoid malignancies (acute leukemias and myelomatosis excluded) during 1969-1987 in the County of Uppsala was calculated on the basis of the regional cancer register and local registers from the only oncological, hematological, dermatological and pathological departments in this well-defined geographical area. Of the 774 patients included, 639 had histopathological specimens available, all of which were re-examined. Seventy-nine patients were diagnosed on the basis of bone marrow investigations (greater than 70% re examined, all had a low-grade non-Hodgkin's lymphoma = NHL) and 54 on fine-needle aspiration biopsies (not re-examined). Seventy-nine of the lymphoma diagnoses were based on autopsy specimens. The overall age standardized incidence was 16.2/100,000/year (NHL: 13.6, Hodgkin's disease = HD: 1.5) according to the Swedish 1970 census (according to world standard population: 10.2); male: 20.9 (12.9) and female: 12.4 (7.9). The annual change in trend was +3.0% +/- 2.6 (NHL: +3.6% +/- 2.4, HD: no change). The omission of the 54 'fine needle cases' led to an overall incidence of 15.0 (9.7) and an annual change in trend of +3.5% +/- 1.9. Among the histopathological specimens, an NHL was found in 524 patients and HD in 69. In 46 registered patients, the diagnosis malignant lymphoma was wrong. The diagnosis changed to NHL in 43 patients registered as HD. PMID- 1622647 TI - Interrelations between cellular DNA content, S-phase fraction, hormone receptor status and age in primary breast cancer. A series of 1,342 consecutively detected tumors. South-East Sweden Breast Cancer Group. AB - Estrogen and progesterone receptors were assessed by an immuno-biochemical method and DNA content was analysed by flow cytometry in a consecutive series of 1,342 frozen breast cancer samples. Forty-six percent of the ER-positive tumors were DNA diploid compared to 23% among ER-negative cases. The proportion of ER-/PR- cases was highest among hypertetraploid tumors (45%) and lowest among DNA diploids (13%). While receptor positivity and DNA ploidy were strongly related, no differences in mean receptor levels were detected when comparing DNA diploid and aneuploid cases of receptor positive tumors. In receptor positive tumors ER content--but not PR content--increased with age. S-phase fraction (SPF) was estimated in 1,165 cases (87%) with an overall mean of 8.6%. Tumors with high S phase levels and DNA hypodiploid tumors were significantly more often found in younger than in older patients. The frequency of DNA hypodiploidy was less than 1% among women older than 75 years, while it was 8% among those aged 40 years or younger. S-phase fraction was inversely related to ER and PR status. However, while mean SPF gradually decreased with increasing levels of PR, no significant difference in S-phase fraction was seen for ER concentrations just above the cut off level for receptor positivity. Tumors positive for both receptors showed the same pattern of DNA ploidy as ER+/PR- tumors while differences in S-phase fraction were observed between the groups. These results support that PR status better than ER status reflects hormone dependent growth in breast cancer. PMID- 1622648 TI - Identification of subgroups with favorable prognosis in breast cancer. AB - The prognostic significance of 16 factors was investigated in a series of 311 women with unilateral, invasive breast carcinoma without distant metastases (M0) and treated with mastectomy. The series consisted of 93% of such cases diagnosed histologically in the city of Turku, Finland, from 1980 to 1984. Mitotic count, histological and nuclear grades, extent of tumor necrosis, axillary nodal status (pN), tumor size (pT), estrogen and progesterone receptor (PR) contents, and S phase fraction were the most powerful single factors (p = 0.0001 or less). Axillary node negative cancers with no or only spotty tumor necrosis (92% of all pN0 cases) were associated with a 96% 5-year survival rate corrected for intercurrent causes. Among the axillary node positive cases the combination of high PR content (greater than 60 fmol/mg protein) and a low mitotic count could identify a subgroup with a 96% 5-year corrected survival rate (25% of all pN+ cases). It is concluded that both pN0 and pN+ breast cancer contain identifiable subgroups with greatly different prognosis. PMID- 1622649 TI - External and interstitial radiation therapy of locally advanced carcinoma of the breast. AB - The present report concerns 164 cases of locally advanced breast cancer (stage III), treated between December 1977 and January 1987. The local therapy consisted exclusively of radiation therapy including external beam irradiation (60Co) up to 45-50 Gy supplemented with a boost, delivered either by interstitial 192Ir (30-40 Gy) or by external irradiation from limited fields (15-22 Gy). Eighty-one patients also received adjuvant systemic chemotherapy. A total of 51 local failures (31%) occurred. The actuarial rate of survival with local tumor control was 53% at 5 years and 49% at 6.5 years. A total of 69 patients developed distant metastases (42%). The actuarial survival without distant failure was 43% at 5 years and 37% at 6 years. The actuarial survival rate at 5 years was 53% and 38% at 7 years. The cosmetic results were excellent in 58 patients and poor in 13 patients (9.7%). The result suggests that stage III breast cancer can be satisfactorily treated with radiation therapy alone as local treatment. PMID- 1622650 TI - Getting free of breast cancer. An eight-year perspective of the relapse-free patients. AB - Twenty-two breast cancer patients who were relapse-free and had no need for cancer-related treatment were interviewed 8 years after mastectomy in order to evaluate their feelings of getting free of breast cancer and the meaning of breast cancer in their lives. The study is a part of an intervention and follow up study of 57 breast cancer patients. Half of the 22 patients still had frequent or occasional thoughts of recurrence and over two-thirds still thought they had not been 'cured' of cancer. More than half of the patients admitted that going through breast cancer had made them more mature. Women who had less thoughts of recurrence belonged to a group that had gone through an eight-week group psychotherapy intervention, were less depressed and had more other illnesses. Women who felt 'cured' had less limitations and restrictions due to cancer and belonged more often to higher social classes than the others. PMID- 1622651 TI - Psychometric validation of the EORTC Core Quality of Life Questionnaire, 30-item version and a diagnosis-specific module for head and neck cancer patients. AB - A cancer-specific self-reporting quality of life questionnaire has been validated. The questionnaire is designed to assess physical functioning, role functioning, cognitive functioning, emotional functioning, social functioning, pain, fatigue, emesis and quality of life by means of multi-item scales, and other disease- and treatment-related symptoms by means of single items. The questionnaire was completed by 126 head and neck cancer patients with a mean age of 67 years. The internal consistency (scale reliability) was satisfactory for all scales but one. Correlations between scales and items assessing the same underlying dimension were also satisfactory. The questionnaire discriminates between patient subgroups and between acute, subacute and late toxicity. Patient compliance was high. The questionnaire provided valuable information, and most of the scales/items functioned well. A few problems were found, especially with the modified visual analogue scales, and minor modifications will be made. PMID- 1622652 TI - Emotional and social aspects of cancer pain. AB - The emotional and social consequences of pain were studied in 93 consecutive in patients, 44 males and 49 females, suffering from cancer-related pain. The methods used were Visual Analogue Scales (VAS), standardized interviews and comprehensive self-questionnaires. Forty-seven patients (51%) experienced certain or pronounced anxiety (4-6 or 7-9 on a 9-grade scale) because of their pain and 66 patients (71%) expressed depressive pain-associated symptoms, which had a high correlation with the intensity of their pain. Physical activities such as movements, dressing/undressing, washing, cooking were hampered in about 2/3 of the patients and mental activities such as reading were significantly disturbed in 48% of the cases. For every social activity listed in the questionnaires (hobbies, seeing friends, etc) most patients reported a decreased activity because of pain and in most cases the decrease correlated significantly with the intensity of the pain. The family roles had changed since the patient could not participate in a usual manner. The study underlines the profound consequences of pain: physical suffering, emotional distress, social handicap and altered family roles. Thus, pain control should be a high-priority matter in palliative care. PMID- 1622653 TI - Urinary polyamines in patients with advanced cervical cancer or pelvic cancer recurrence during and after radiotherapy. AB - The urinary excretion of polyamines was evaluated before, during and after radiotherapy in 16 patients with advanced squamous cell carcinoma of the uterine cervix (stage IIb or IIIb) and in 7 cases with pelvic recurrence after surgery for various types of carcinoma. The concentration of spermidine was significantly higher in the patients with primary tumors than in those with recurrent tumors. After the first radiation fractions putrescine increased in the patients with primary tumors whereas it decreased in patients with recurrent tumors. The values tended to return to baseline levels with time following treatment initiation. Polyamine increased markedly during treatment in patients who remained disease free for at least 5 years but not in the patients with progressive disease or relapse. The results suggest a different polyamine metabolism and a different response to radiotherapy of recurrent tumors compared to primary tumors. The increase of urinary polyamines, but not the baseline values, seemed to be correlated to the response after radiotherapy. PMID- 1622654 TI - Carcinoembryonic antigen in anal carcinoma. AB - Patients with squamous cell carcinoma of the anal canal occasionally present with an elevated level of carcinoembryonic antigen (CEA) in serum. The present study was performed to evaluate the clinical importance of this observation. Serum CEA was measured in 106 patients prior to chemo- and radiotherapy and during follow up. Twenty patients had elevated serum CEA level before treatment. In 6 of 12 cases, serum CEA did not normalize after successful treatment and in 4 of 7 cases it rose no further despite progressive disease. CEA-positive tumours were more often poorly differentiated than CEA-negative tumours. There was no significant correlation between serum CEA, tumour CEA and prognosis. We conclude that measurement of serum CEA and staining of tumour CEA lack clinical importance. PMID- 1622655 TI - Weekly oral idarubicin in advanced prostatic cancer. A phase II study. AB - Twenty-five patients with advanced prostatic cancer progressing after one course of endocrine treatment entered a phase II study of weekly administration of 30 mg Idarubicin orally. Twenty-two patients were evaluable for response and partial response (PR) was noted in 2 patients and stable disease (NC) in 10 patients. Median survival was 31 weeks and median time to progression was 14 weeks. Twenty three patients were eligible in a score system combining analgetic consumption and pain reduction measured on a Visual Analogue Scale (VAS) and 30% achieved a subjective response. Fifteen patients fulfilled treatment with the planned dose and 10 patients had dose reduction to a median of 23.8 mg Idarubicin. Haematological toxicity was greater than or equal to grade 3 (WHO) in 20% of the patients. Non-haematological toxicity was dominated by nausea/vomiting with 48% grade 3 (WHO). In conclusion, Idarubicin seems of limited value in the treatment of patients refractory to first line endocrine treatment. PMID- 1622656 TI - Squamous cell carcinoma of the oropharynx. Results of primary radiotherapy. AB - During the six-year period in 1979 through 1985, 226 patients (67 females and 159 males) with squamous cell carcinoma of the oropharynx were treated at the Finsen Institute in Copenhagen. Ages ranged from 35 to 86 years with an average of 64 years for females and 61 years for males. The primary tumour was most often situated in the lateral wall (55%) and the anterior wall (25%). Thirty-nine per cent of the tumours were in stage III and 40% in stage IV. The primary treatment was radiotherapy, in this period given with three different treatment schedules, one continuous and two split-course. The 5-year crude survival rate in the total material was 36% and the corrected 5-year survival rate 45%. Females had a higher loco-regional control rate than males, but there was no significant differences between the sexes concerning survival. The tumour stage (IUCC, 1978) was an important prognostic factor for both loco-regional control and survival. No significant differences could be found between the three treatment schedules concerning loco-regional control or survival. PMID- 1622657 TI - Cisplatin and hyperthermia treatment of a C3H mammary carcinoma in vivo. Importance of sequence, interval, drug dose, and temperature. AB - The effect of combining cisplatin and hyperthermia was investigated in a C3H mammary carcinoma in vivo, using a regrowth delay assay. Cisplatin (6 mg/kg) was given i.p. at intervals ranging from 24 h before to 24 h after a 43.5 degrees C/60 min treatment. A supra-additive effect was obtained by giving cisplatin 15 min before heat, whereas an additive effect was obtained at all other intervals. The importance of cisplatin dose and heating temperature were investigated by giving variable cisplatin doses (2-8 mg/kg) 4 h or 15 min before a 60 min heating at temperatures in the range 40.5-43.5 degrees C. Linear relationships between length of regrowth delay and cisplatin dose were obtained both for cisplatin alone and for the combined treatment. The effect of the combined treatment could therefore be quantitated by a ratio (ER) between the slopes of dose-response curves. The ER values for cisplatin give 4 h before a 60 min heating at 42.5 or 43.5 degrees C were not significantly different from 1 (p greater than 0.5). In contrast, significant ER values were obtained above 40.5 degrees C (p less than 0.05) for cisplatin given 15 min before heat. The data demonstrates the possibility of achieving chemosensitization at clinically relevant temperatures. PMID- 1622658 TI - Fractionated irradiation and early changes in noradrenaline induced potassium efflux (86Rb+) in rat parotid gland. AB - The effects of fractionated irradiation on the electrolyte fluid secretion from rat parotid gland were studied. Secretion was measured as noradrenaline stimulated potassium efflux in vitro with 86Rb+ as tracer for potassium. The irradiation was delivered either as a five-day schedule (total dose 20, 25, 30, 35, 40, 45 Gy) or a two-day schedule (total dose 24, 32 Gy). The noradrenaline stimulated efflux was decreased in comparison with contralateral controls 10 days after the last irradiation. The effect was dose-dependent. Based on the data available, alpha/beta ratio of the used system was calculated to about 20 Gy, which corresponds to other results regarding early radiation effects. PMID- 1622659 TI - Treatment response to natural leukocyte interferon-alpha in relapsing malignant insulinoma with severe hypoglycemia. PMID- 1622660 TI - Cardiac tamponade in testis cancer--an autopsy case. PMID- 1622662 TI - 'References'. PMID- 1622661 TI - 'Post-qualification training for dental hygienists'. PMID- 1622663 TI - 'The Sick Dentist Trust'. PMID- 1622664 TI - 'Community dentistry in the dental faculties'. PMID- 1622665 TI - 'Cut in the GDS fee scale'. PMID- 1622666 TI - Community dentistry in the dental faculties. PMID- 1622667 TI - 'Osteomyelitis following third molar surgery'. PMID- 1622668 TI - 'The prescription and timing of bitewing radiography in the diagnosis and management of dental caries: contemporary recommendations'. PMID- 1622669 TI - Needle guard. PMID- 1622670 TI - Oral infections in the immunocompromised patient. AB - The number of immunocompromised patients is increasing because of iatrogenic immunosuppression and HIV infection. Most have T lymphocyte defects and are prone to develop persistent and severe fungal and viral infections. Oral candidosis and peri-oral herpes simplex infections are particularly common. Other oral lesions may be seen: mouth ulceration is common and periodontal health is impaired. PMID- 1622671 TI - The Scottish Health Boards' Dental Epidemiological Programme: initial surveys of 5- and 12-year-olds. AB - The Scottish Health Boards' Dental Epidemiological Programme, a joint venture between the Scottish Chief Administrative Dental Officers and the Dental Health Services Research Unit at the University of Dundee, was instigated in 1987 in response to the Chief Dental Officer's concern at the lack of any coordinated dental health information about children residing in the 15 Scottish Health Board areas. Each year a standardised dental survey of a random sample of children is now undertaken across Scotland. This paper reports, principally, the caries results of the first three surveys of 5, 12 and 5-year-olds undertaken at the end of 1987, 1988 and 1989, respectively. Marked variations in caries prevalence were found in different parts of Scotland, higher levels being recorded in the urbanised central belt and in the West. While there have been overall improvements since 1983, caries prevalence in Scotland remains substantially higher than in many other parts of the UK (mean DMFT for 12-year-olds in 1988 = 2.23, mean dmft for 5-year-olds in 1989 = 2.82), with 67.8% of 12-year-olds and 59.2% of 5-year-olds (in 1988 and 1989, respectively) still suffering from dentinal caries or past caries experience (DMFT/dmft greater than 0) when assessed by clinical examination alone. No continued improvement in caries prevalence was seen in the 1989 survey of 5-year-olds compared to the 1987 examination. Continued monitoring of this situation is indicated. PMID- 1622672 TI - Prevention of endocarditis: communication between doctors and dentists. AB - Successful implementation of guidelines to prevent infective endocarditis (IE) depends upon the dental practitioner being aware of which of his patients are at risk. This was studied by sending a questionnaire to at risk patients and their dentists in the Grampian area. Of 145 respondents (53% response rate) with predisposing cardiac disorders, only 63 reported having seen their dentist in the past 2 years, although for dentate patients 47/61 had seen a dentist in the past 2 years. The dentists of 59 of these cases were then surveyed and replies received in 53 cases. Nineteen had no record of the patient having a cardiac disorder. In only 17 of the remaining cases was information on the cardiac disorder well enough recorded to warrant prophylaxis for at risk procedures. The dentist was usually told of the disorder only by the patient. Sixty-three per cent of dentists felt that communication between them and the patient's doctor was unsatisfactory. It is necessary to improve doctor/patient/dentist communication so that current recommendations on prophylaxis can be implemented to the full. This should be done through the patient's GP or consultant, who should communicate directly with the dentist. Details could also be inserted on warfarin cards and 'cardiac alert cards' expanded. PMID- 1622674 TI - 'Orthodontic relapse'. PMID- 1622673 TI - The specialisation of oral surgery in general practice. AB - Much has been written recently on the subject of introducing a specialist title in oral surgery and the establishment of specialist oral surgery practices. The aim of my elective was to conduct a literature review, interview general practitioners involved in oral surgery, and examine the feasibility of undertaking oral surgery in a specialist practice. PMID- 1622675 TI - Fit to train? PMID- 1622676 TI - Light check. PMID- 1622677 TI - The pathophysiology of cardiorespiratory arrest and principles of post resuscitation intensive care. AB - Oxygen supply to the tissues is dependent on both cardiac output (which is determined by blood volume and myocardial function) and the oxygen tension of arterial blood (which reflects respiratory status). Abnormalities of these parameters may occur individually or together to progress ultimately to combined cardiorespiratory collapse. Life support measures are then required to restore the oxygen supply to vital organs, such as the brain, heart, kidneys and liver while attempts to restore normal cardiorespiratory status are made. Survival following cardiorespiratory arrest is enhanced if resuscitation is promptly instituted by skilled resuscitators, and a clear understanding of the mechanisms of cardiorespiratory collapse are essential to the efficient management of these patients. PMID- 1622678 TI - Compliance with infection control procedures in a dental hospital clinic. AB - Dental hospital staff and students were observed during clinical work for their compliance with infection control procedures, as recommended by the British Dental Association. A total of 183 contacts between health care worker and patient were scrutinised during December 1990. Nearly all health care workers (96%) wore gloves to carry out dental treatment, but in some cases gloves were neither changed nor hands washed between patients. Only one half wore protective eyewear and about one third (38%) wore no mask. Some dental surgery assistants used heavy duty gloves and some even scrubbed dirty dental instruments without wearing any gloves. Strict audit is clearly needed in every clinical setting in order to ensure compliance with infection control. PMID- 1622679 TI - Dentistry in Dohnavur, 1955-1992. AB - In October 1955 I arrived here in Dohnavur, India, as a young, reluctant dental missionary! My first hurdle was to learn the language--Tamil--said to be one of the most difficult languages in the world. For the first year I was given one hour 'off' language study to do dentistry. In that hour I began to see our large family, which then numbered about 900. In the second year, still in a room with only the dental chair and a foot engine for temporary use, I spent half the time in dentistry and continued to learn Tamil the rest of the time. The dental surgery was built, and the equipment that I had brought with me from UK had been installed, and on December 17, 1957, we had the dedication of the dental surgery and I had the joy of having my parents with me from the UK for that special day. PMID- 1622680 TI - A new dental health project in Zambia. AB - In Zambia's population of 8 million, 69% are under 24 years of age. The country has a crippling foreign debt, and consequently public services are poorly funded. From March this year my wife and I have been working in Zambia. I have been asked to establish and develop a dental service based at Mukinge Hospital in the North Western Province. Zambia borders eight other countries on the central African plateau and lies at an altitude of between 3000 and 6000 feet. PMID- 1622681 TI - 'Low-energy lasers in dentistry'. PMID- 1622682 TI - 'Alternatives to toothpaste'. PMID- 1622683 TI - Hazards in the dental surgery and safe practices. PMID- 1622684 TI - Team tactics. PMID- 1622685 TI - 2-(Trimethylsilyl)ethyl glycosides. Synthesis of the asialo-GM1-tetrasaccharide, spacer glycoside, and BSA and Sepharose glycoconjugates. AB - The tri and tetra-saccharide glycosides beta-D-GalNAc-(1-4)-beta-D-Gal-(1-4)-beta D-Glc-1-OTMSEt and beta-D-Gal-(1-3)-beta-D-GalNAc-(1-4)-beta-D-Gal-(1-4)-beta-D Glc-1-OT MSEt (asialo-GM1) have been synthesized by sequential glycosylations of a suitably protected 2-(trimethylsilyl)ethyl (TMSEt) lactoside with 3,4,6-tri-O acetyl-2-deoxy-2-phthalimido-beta-D-galactopyranosyl chloride and 2,3,4,6-tetra-O acetyl-beta-D-galactopyranosyl bromide. The tetrasaccharide glycoside was transformed into the corresponding hemiacetal sugar as well as the 1-chloro sugar. The latter was used for glycosylation of 2-bromoethanol. The resulting glycoside was used to alkylate methyl 3-mercaptopropionate and the resulting spacer glycoside was used for the preparation of the title glycoconjugates. PMID- 1622686 TI - Intracoronary stents. PMID- 1622687 TI - Diagnostic techniques in suspected thoracic aortic dissection. PMID- 1622688 TI - Exercise training as therapy for chronic heart failure. PMID- 1622689 TI - Occurrence of valvar heart disease in acute rheumatic fever without evident carditis: colour-flow Doppler identification. AB - OBJECTIVE: To determine the frequency of occurrence of mitral and aortic valvar regurgitation in rheumatic children in whom there was no evidence of carditis acutely or at an earlier attack. DESIGN: Colour flow Doppler imaging was used in a non-randomised study of sequentially admitted children who met the criteria for acute rheumatic fever without clinically evident carditis and patients in whom the disease was quiescent after a previous attack of rheumatic fever. Two separate control groups were used for comparison of the echocardiographic findings, and a group of patients with confirmed rheumatic carditis was included for comparison of acute phase and antistreptococcal reactants. SETTING: A general hospital with the only paediatric inpatient department in Qatar. PATIENTS: From November 1988 to October 1990, 11 children were studied during the acute rheumatic period. In seven additional children the disease was quiescent when they were studied 18 to 36 months after a documented episode of acute rheumatic fever in which there was no evidence of carditis. The control patients were all studied during the same period. MAIN OUTCOME MEASURE: Detection of mitral and aortic regurgitation in patients without clinical evidence of rheumatic carditis in the acute or quiescent stages of the disease. RESULTS: Mitral or mitral and aortic regurgitation was found in 10 of the 11 children studied in the acute rheumatic period. None had a murmur or other evidence of carditis. In all the cases studied the valvar insufficiency was mild. Four of the children studied late in the quiescent period had either aortic or mitral insufficiency by colour flow Doppler evaluation; two children who had previously had valvar insufficiency no longer showed this, and one child without positive findings in the acute phase remained without insufficiency. None of the non-rheumatic control subjects showed mitral or aortic regurgitation. CONCLUSIONS: Colour flow Doppler imaging is a useful method of identifying subclinical mitral and aortic valvar disease at all stages of rheumatic fever when carditis cannot be otherwise detected and is a valuable addition to current diagnostic criteria. PMID- 1622690 TI - Aortic valve regurgitation and the congenitally bicuspid aortic valve: a clinico pathological correlation. AB - OBJECTIVE: To investigate the morphology of congenitally bicuspid aortic valves causing pure valve regurgitation. DESIGN: A case series collected over five years. SETTING: An academic hospital. PATIENTS AND METHODS: One hundred and forty eight excised congenitally bicuspid aortic valves. The morphological findings were correlated with sex, age, clinical history, and data on haemodynamic function before operation. Pure valve regurgitation was defined as grade 3-4/4 with a gradient less than 30 mm Hg. Aortic root dilatation was evaluated angiographically or echocardiographically or both. RESULTS: Three types were recognised: valves that were purely bicuspid (23%), bicuspid valves with a raphe (34%), and valves with an additional indentation of the free edge of the conjoined cusp (43%). In 14 cases pure valve regurgitation was present. Dilatation of the aortic root was present in 47 cases. The relative risk for regurgitation when the aortic root was dilated (compared with no dilatation) was 3.99. The relative risk for valve regurgitation when there was indentation of the conjoined cusp (compared with no indentation) was 4.95. The mean age at operation in patients with pure regurgitation was 56 years, which is significantly younger (p = 0.0008) than that of patients with a congenitally bicuspid valve with combined valve stenosis and regurgitation (64.7 years). CONCLUSIONS: Congenitally bicuspid aortic valves with a central indentation of the free edge of the conjoined cusp seem particularly likely to develop pure aortic valve regurgitation. PMID- 1622691 TI - Can mitral regurgitation after balloon dilatation of the mitral valve be predicted? AB - OBJECTIVE: To determine which factors predict the occurrence of mitral regurgitation after balloon dilatation of the mitral valve for rheumatic stenosis. DESIGN: Analysis of a case series of patients with rheumatic mitral valve stenosis who had had successful balloon dilatation of the mitral valve. SETTING: A tertiary care centre with an experience of over 150 balloon dilatations of the mitral valve. PATIENTS: 70 young patients with non-calcified rheumatic mitral stenosis, who had undergone successful balloon dilatation of the mitral valve. No patient had mitral regurgitation or atrial fibrillation before dilatation. INTERVENTION: Dilatation of the mitral valve by the transvenous, transatrial double balloon technique. MAIN OUTCOME MEASURE: Development of mitral regurgitation after balloon dilatation of the mitral valve and its relation to age, mitral valve area before dilatation and after dilatation, the degree of mitral subvalvar pathology, and the size of balloon used for dilatation. RESULTS: In 10 patients (14%) mitral regurgitation developed after balloon dilatation of the mitral valve. No statistically significant differences were found between patients who did not develop regurgitation and those who did in terms of age (mean (SD)) (19.9 (6.46) v 19.4 (5.5)), mitral valve area before dilatation (1.05 (0.33) v 0.94 (0.4) cm2) and after dilatation (2.52 (1.06) v 2.45 (1.1) cm2), mitral subvalvar pathology assessed by the mitral subvalvar distance ratio (0.116 (0.03) v 0.118 (2.32), or balloon diameter corrected for body surface area (21.37 (3.5) v 20.57 (2.32) mm/m2. CONCLUSIONS: In this subset of children and young adults with non-calcified mitral stenosis, none of the morphological, technical, or patient characteristics studied predicted the development of mitral regurgitation after balloon dilatation. The low incidence of mitral regurgitation may have reduced the discriminatory power of this study. None the less, the means and standard deviation for each factor in each group suggest that even in a larger sample size the variables would have little predictive capacity. PMID- 1622692 TI - Histological changes in the aortic valve after balloon dilatation: evidence for a delayed healing process. AB - OBJECTIVE: To investigate whether balloon dilatation of the aortic valve induces long-term macroscopic or histological changes or both to explain the restenosis process. DESIGN: Prospective study of 39 consecutive patients. Sixteen later (mean (SD) 12 (10) months) required operation. This non-randomised subgroup was compared with 10 patients who had aortic valve replacement without prior dilatation. SETTING: University cardiology and cardiac surgery centre and pathology department. PATIENTS: 16 patients who had aortic valve replacement because of failure of or restenosis after balloon dilatation of the aortic valve. Twelve resected valves were examined. INTERVENTIONS: Percutaneous balloon dilatation of the aortic valve (maximal balloon size: trefoil 3 x 12 mm balloon or bifoil 2 x 19 mm balloon) and surgical inspection before excision of the aortic valve leaflets during open-chest aortic valve replacement. Fixation, decalcification, and staining for histology. MAIN OUTCOME MEASURES: Presence of long-term pathological changes in the resected valve and their relation to restenosis after balloon dilatation. RESULTS: Macroscopically the previously dilated valves were indistinguishable from valves from the patients who had valve replacement only. Microscopically, the dilated aortic valves showed areas of young scar tissue that were not seen in a control group of surgically excised stenotic aortic valves. This persistent scarring reaction was seen around small tears or lacerations of the collagenous valve stroma, fractures in calcified areas, and splits in commissures. Young scar tissue without collagenisation was still present 24 months after dilatation. CONCLUSION: Organisation and collagenisation of scar tissue develops slowly after balloon dilatation of the aortic valve. This prolonged scarring reaction may explain the late development of restenosis in some patients. PMID- 1622693 TI - Failure of balloon dilatation of the pulmonary valve in carcinoid pulmonary stenosis. AB - BACKGROUND: Carcinoid heart disease typically results in pulmonary stenosis and tricuspid incompetence. Percutaneous balloon dilatation is an effective treatment for congenital pulmonary stenosis and has been applied successfully to tricuspid stenosis caused by carcinoid heart disease. The value of balloon dilatation of the pulmonary valve in carcinoid pulmonary stenosis was assessed. METHODS: Two patients with severe congestive heart failure secondary to carcinoid heart disease and with documented pulmonary stenosis had balloon dilatation of the pulmonary valve. In both cases tricuspid regurgitation was also present together with reduced cardiac output. RESULTS: The procedure was technically successful in both patients. One patient experienced symptomatic benefit for two months and the other experienced no improvement. Both patients subsequently required combined tricuspid and pulmonary valve replacement from which good results and symptomatic improvement were obtained. CONCLUSION: Though balloon dilatation of the pulmonary valve is technically feasible it is unlikely to provide useful palliation in carcinoid heart disease. Valve surgery should be considered in patients in whom the malignancy is controlled but carcinoid heart disease is producing drug resistant congestive heart failure. PMID- 1622695 TI - Closing sounds and related complaints after heart valve replacement with St Jude Medical, Duromedics Edwards, Bjork-Shiley Monostrut, and Carbomedics prostheses. AB - OBJECTIVE: To measure the noise produced and related subjective complaints after implantation of four different mechanical heart valve prostheses and to identify further factors related to the patient and prosthesis that influence noise generation and complaints. DESIGN: Sound pressure was measured 5 and 10 cm and 1 m from the point of maximal impulse on the body surface by a calibrated meter in quiet rooms with either a decibel(A) filter or octave filters. The patients were asked about their complaints and examined physically. SETTING: The measurements were conducted in silent rooms of ear, nose, and throat departments. The patients had been operated on either in a university hospital or a community hospital. MAIN OUTCOME MEASURES: Sound pressures of frequency bands and sound pressures measured in dB(A) at various distances. Complaints registerd were: sleep disturbance, disturbance during daytime, "wants a less noisy prosthesis," and "can hear the closing click". PATIENTS: 143 patients after heart valve replacement with St Jude Medical (n = 35), Duromedics Edwards (n = 38), Carbomedics (n = 34) and Bjork-Shiley Monostrut (n = 36) prostheses operated on between 1984 and 1988 were matched for valve position, ring size, and body surface area. RESULTS: Duromedics Edwards (33.5 (6) dB(A)) and Bjork-Shiley Monostrut valves (31 (4) dB(A)) were significantly louder than St Jude Medical (24 (4) dB(A)) and Carbomedics (25 (6) dB(A)) prostheses (p = 0.0001) (mean (SD)). The louder valves were significantly more often heard by the patients (p = 0.0012) and caused more complaints both during sleep (p = 0.024) and during the daytime (p = 0.07). Patients with these valves were more likely to want a less noisy valve (p = 0.0047). Patients with symptoms were younger, had better hearing, and were more likely to be in sinus rhythm. As well as the type of prostheses, the valve diameter and body height also had an effect on sound emission. CONCLUSIONS: The intensity of the closing click of mechanical valve prostheses was significantly different for various designs. Patient complaints were related to the objectively measured sound pressure. Noise production should be considered when a mechanical valve is selected. PMID- 1622694 TI - Percutaneous balloon dilatation of the mitral valve in patients who were unsuitable for surgical treatment. AB - OBJECTIVE: To assess the effects on haemodynamic function and symptoms of percutaneous balloon dilatation of mitral stenosis in patients unable to undergo surgical treatment because of associated medical/cardiac problems. DESIGN: A review of clinical outcome in 28 patients (of 108 undergoing balloon dilatation of the mitral valve) who were unsuitable for surgery. SETTING: A tertiary cardiac referral centre: some patients referred were from other cardiac centres in Scotland. PATIENTS: 28 patients judged by cardiac surgeons to be unsuitable for valve replacement or valvotomy because of respiratory disease (15 patients), nonmitral cardiac disease (6), multi-organ impairment (5), psychiatric problems (1) or dense intrathoracic adhesions (1). INTERVENTIONS: Percutaneous anterograde balloon dilatation of the mitral valve with polyethylene/polyvinyl balloons in 20 patients and the Inoue balloon in eight patients. MAIN OUTCOME MEASURES: Haemodynamic variables were measured before and immediately after mitral valve dilatation. Patient survival and symptom class (New York Heart Association) were followed for a year after the procedure. RESULTS: Dilatation at the mitral orifice was achieved in all cases. The mean (SD) pressure drop across the valve fell from 13.9 (5.3) to 5.6 (2.5) mm Hg, cardiac output rose from 3.18 (1.02) to 3.96 (2.5) l/min, and valve area increased from 0.78 (0.32) to 1.58 (0.56) cm2. The procedure was well tolerated by most patients, even those with metabolic/electrolyte disturbance, severe obstructive airways disease, myocardial impairment, and coronary disease. In three patients a small shunt developed at the atrial level: none developed severe mitral reflux. The two patients who required assisted ventilation died soon after the procedure and in one patient with severe coronary artery disease myocardial infarction developed and she died in cardiogenic shock. Early symptomatic improvement was reported by 23 of the 25 survivors, though the increase in exercise capacity was often limited by their non-mitral disease. At one year follow up a further 6 patients had died because of their additional disease: 15 continued to show symptomatic improvement. CONCLUSIONS: Percutaneous balloon dilatation of the mitral valve is a useful new option in patients who are too ill to undergo cardiac surgery; but longer term benefit can be limited by the associated disease. PMID- 1622696 TI - Doppler sonographic evaluation of mechanical and bioprosthetic mitral valve prostheses during exercise with a rate corrected pressure half time. AB - OBJECTIVE: To compare the effect of exercise on pressure half time in patients with mechanical or bioprosthetic mitral valves. A relative pressure half time (pressure half time as a percentage of RR interval) was used in an attempt to correct for the shortening of the diastolic time interval caused by the increase in heart rate during exercise and thus to uncover the effects of valve design on pressure half time during exercise. PATIENTS: Twenty clinically stable (New York Heart Association grade I-II) patients with mechanical (n = 12) or bioprosthetic (n = 8) mitral valves (median age 51) years. The median time since valve replacement was 42 months. METHODS: Continuous wave Doppler echocardiography from the apical view at rest and during moderate supine bicycle exercise (50 W). RESULTS: During exercise the mean (SD) heart rate increased from 79 (12) to 101 (12) beats per minute (95% confidence interval (95% CI) of difference, 15 to 29/min) and the peak pressure gradient from 11 (5) to 18 (6) mm Hg (95% CI of difference 5 to 9 mm Hg). The pressure half time decreased from 114 (30) to 78 (26) ms (95% CI of difference (30-42 ms). There was no difference between the valve types. The relative pressure half time remained unchanged in patients with mechanical valves during exercise (13 (4) rest and 13 (5)% exercise, respectively) and decreased in patients with bioprostheses (17 (3) and 12 (3)%, respectively (95% CI of difference 2 to 8%, p = 0.025). CONCLUSIONS: In patients with mechanical mitral valves the decrease in the pressure half time during exercise is probably mostly the result of the shortening of the diastolic time interval with increasing heart rate whereas in patients with bioprosthetic valves an increase in functional valve area may contribute to the shortening of pressure half time during exercise. PMID- 1622697 TI - Exercise capacity after complete repair of tetralogy of Fallot: deleterious effects of residual pulmonary regurgitation. AB - OBJECTIVE: To determine the effects of residual pulmonary regurgitation on exercise tolerance after complete repair of tetralogy of Fallot. DESIGN: Prospective study of symptom free patients more than five years after complete repair. Graded exercise performance was measured with standard Bruce protocol. Maximal oxygen uptake and ventilatory anaerobic threshold were measured by respiratory mass spectrometry. Measurement of pulmonary regurgitant fraction was from pressure-volume loops constructed from measurements of right ventricular volume obtained from biplane angiograms and simultaneous pressures measured with a micromanometer. SETTING: Tertiary referral centre. PATIENTS: 16 patients were studied. Two patients had been excluded because of residual cardiac lesions or inadequate data from cardiac catheterisation. Four were later excluded because they failed to reach a respiratory quotient of greater than 1.0 during graded exercise. RESULTS: There was a significant negative correlation between the degree of residual regurgitation and both total duration of exercise and maximal heart rate achieved. Maximal heart rate and total duration of exercise were significantly lower in the patients than in normal controls. Patients with an abnormal maximal oxygen uptake (less than 85% of the predicted normal value) had significantly greater residual pulmonary regurgitation than those in whom oxygen uptake was normal. CONCLUSIONS: Impaired exercise capacity after complete repair of tetralogy of Fallot is directly related to the degree of residual pulmonary regurgitation. These data should be taken into account when deciding the optimal timing and nature of corrective surgery. PMID- 1622698 TI - Regional blood flow in chronic heart failure: the reason for the lack of correlation between patients' exercise tolerance and cardiac output? AB - BACKGROUND: In patients with chronic heart failure there is no relation between cardiac output and symptom limited exercise tolerance measured on a bicycle or treadmill. Furthermore, the increase in cardiac output in response to treatment may not be matched by a similar increase in exercise tolerance. More important in determining exercise capability is blood flow to skeletal muscle. This implies that the reduction in skeletal muscle blood flow is not directly proportional to the reduction in cardiac output and that there are regional differences in blood flow in patients with heart failure. METHODS: Cardiac output and regional blood flow measured in 30 patients with chronic heart failure were compared with values obtained from 10 healthy controls. Measurements were made at rest and in response to treadmill exercise and were all made non-invasively. RESULTS: Cardiac output was lower in the patients at rest and during exercise. Blood flow in the superior mesenteric and renal arteries was also lower in the patients and represented a different proportion of cardiac output than in the controls. In response to exercise the increase in blood flow to the calf and therefore to skeletal muscle, was reduced in the patients. In the patients there was no correlation between resting cardiac output and blood flow in the superior mesenteric artery, renal artery, or calf. CONCLUSIONS: Because blood flow to skeletal muscle and to the kidneys is likely to be important in determining patients' symptoms this factor may explain why central haemodynamic variables do not correlate with the exercise tolerance in patients with chronic heart failure. PMID- 1622699 TI - Decreased cardiac parasympathetic activity in chronic heart failure and its relation to left ventricular function. AB - BACKGROUND: Activation of the sympathetic nervous system has been extensively studied in patients with chronic heart failure, but the parasympathetic nervous system has received relatively little attention. The objective in this study was to investigate cardiac parasympathetic activity in chronic heart failure and to explore its relation to left ventricular function. METHODS: Heart rate variability was measured from 24 hour ambulatory electrocardiograms by counting the number of times each RR interval exceeded the preceding RR interval by more than 50 ms (counts). This method provided a sensitive index of cardiac parasympathetic activity. RESULTS: Mean (range) of counts were: waking 48 (1 275)/h, sleeping 62 (0-360)/h, and total 1310 (31-7278)/24 h. These were lower than expected, and in 26 (60%) of the 43 patients counts fell below the lower 95% confidence intervals (95% CI) for RR counts in normal subjects. A significant correlation between total 24 hour RR counts and left ventricular ejection fraction was present (r = 0.49, p less than 0.05). CONCLUSIONS: These results indicate that most patients with chronic heart failure have reduced heart rate variability and therefore reduced cardiac parasympathetic activity. The degree of parasympathetic dysfunction is related to the severity of left ventricular dysfunction. This may be relevant to the high incidence of ventricular arrhythmias and poor prognosis of patients with chronic heart failure. PMID- 1622700 TI - Lack of variation in venous tone potentiates vasovagal syncope. AB - OBJECTIVE: To investigate the peripheral venous response to head up tilting in malignant vasovagal syndrome. PATIENTS: 31 Patients with unexplained syncope or dizziness referred from the cardiology department. METHODS: Changes in calf venous volume were studied by a radionuclide technique during 45 degrees head up tilt testing. RESULTS: During tilt testing six patients became syncopal but 25 were symptom free. The syncopal group had greater increases in calf venous volume after the change in posture and perhaps more importantly considerably less variability in the venous volume during the tilted period. CONCLUSIONS: The venous response was different in the syncopal patients. The lack of response of the peripheral venous circulation to changes in the central circulation may be responsible for triggering the Bezold-Jarisch reflex and malignant vasovagal syncope. PMID- 1622702 TI - Streptokinase treatment of a thrombosed Bjork-Shiley prosthesis in the aortic position. AB - Dysfunction of a mechanical prosthetic valve caused by thrombus formation is usually treated surgically. A patient with a thrombosed Bjork-Shiley valve in the aortic position was treated successfully with intravenous streptokinase. The considerable improvement in the patient's clinical condition and the phonocardiographic, echocardiographic, and cinefluoroscopic evidence of normalisation of prosthetic valve function established the efficacy of thrombolytic therapy of a thrombosed prosthetic valve in this patient. PMID- 1622701 TI - Short-term and long-term treatment with propafenone: determinants of arrhythmia suppression, persistence of efficacy, arrhythmogenesis, and side effects in patients with symptoms. AB - OBJECTIVE: To assess the clinical criteria predicting the short and long-term efficacy of propafenone, an agent with class IC antiarrhythmic activity and a broad pharmacological profile. DESIGNS: Prospective study of propafenone at doses of 450 to 900 mg/day during a six week dose titration period (including a placebo phase with two separate 24 Holter recordings). Responders to treatment were followed for one year. PATIENTS: One hundred patients with frequent ventricular arrhythmias (greater than 30 extrasystoles/h) of Lown class III and IVA/B and without evidence of myocardial infarction within the past six months. ANALYSIS: Multivariate regression analysis of spontaneous arrhythmia variability and of different clinical variables to determine the short and long-term efficacy and safety of propafenone. MEASUREMENTS AND MAIN RESULTS: Propafenone 450 mg/day was effective in 30/100 patients (30%), and at 600 mg/day another 14 responded. The efficacy of propafenone correlated with a low spontaneous arrhythmia variability and, as shown by multivariate analysis, with a lower patient age (p less than 0.05). When the dose was increased to 900 mg/day a further six (12%) patients responded. However, with increasing doses of propafenone, the one year probability of effective treatment decreased from 86% (450 mg/day) to 67% (600 mg/day) and to 44% (900 mg/day). After restudying the patients at three, six, and 12 months and after dose adjustment in 11/44 patients (25%), 31 patients (70%) remained responders. Loss of permanent antiarrhythmic efficacy was best predicted by the initial dose that achieved a response. No patient died suddenly or had arrhythmogenic effects during Holter monitoring. Side effects occurred in 36% of patients but these rarely limited long-term treatment. CONCLUSIONS: A younger age, low spontaneous arrhythmia variability, and particularly a low titration dose were the best predictors of the short and long term efficacy of propafenone. All other responders should have repeated Holter recordings during the first year of treatment. PMID- 1622703 TI - Infected interventricular Teflon patch: repair and closure of fistula with omentum. AB - A pericardiocutaneous fistula five years after repair of a rupture of the ventricular septum was managed by removing all foreign material (Teflon). The resulting defect was repaired with part of the central tendon of the diaphragm and a pedicle of omentum was used to cover the heart. This radical approach was found necessary after other measures, including surgical excision of the fistula, had failed. PMID- 1622704 TI - Subaortic stenosis caused by an unusual fibrous blood-filled cyst of the left ventricle with outflow tract obstruction associated with a ventricular septal defect. AB - A large blood-filled cyst formed from a fibrous tissue tag of a right ventricular septal aneurysm was successfully resected. This cyst, which was causing subaortic stenosis, was attached to the margin of the closed ventricular septal defect and not to the mitral valve itself nor the papillary muscle of the left ventricle. PMID- 1622705 TI - The natural course of osteoarthritis of the hip due to subluxation or acetabular dysplasia. AB - In 59 patients, 86 hips with subluxation or hip dysplasia were examined to determine the natural course of the condition and select suitable treatment. Thirty-three percent of the joints (13/39 hips) developed early osteoarthritis from pre-osteoarthritis within an average term of 9.2 years, while the remaining, sixty-six percent (31/47 hips) developed advanced-stage osteoarthritis from early osteoarthritis within an average term of 7.8 years. Patients were classified into advanced and non-advanced groups according to radiographic analysis of the advanced groups according to radiographic analysis of the advance of the disease and statistical analysis was performed. In pre-osteoarthritis, centre-edge angle, slope of the acetabular roof, acetabular head index, acetabular depth ratio and Japanese Orthopaedic Association (JOA) hip score were significant predictors, while in early osteoarthritis, a broken Shenton's line, cranial joint space and JOA score were significant. On the basis of multiple parameters, formulas for predicting development in patients with pre-osteoarthritis, those with early osteoarthritis, and all patients together were established, with an accuracy of 87%, 71%, and 68%, respectively. PMID- 1622706 TI - A surgical approach in total shoulder arthroplasty. AB - The long deltopectoral approach promoted by Neer is the standard for performing a total shoulder arthroplasty. However, this exposure is inadequate for preparation and bone grafting of the glenoid cavity or repairing an associated large rotator cuff tear. In the anatomy laboratory we looked for an alternative approach to the glenohumeral joint which would accommodate these difficulties. Afterwards we used this approach in 7 of 13 patients in whom a Biomet Bio-modular shoulder arthroplasty was planned. The study is prospective with a 1-year follow-up of 12 cases. PMID- 1622707 TI - Bad results after anterior advancement of the tibial tubercle for patello-femoral pain syndrome. AB - Seventy-one patients with patello-femoral pain syndrome were re-examined an average of 10 (range 8-12) years after anterior advancement of the tibial tuberosity. The clinical results were excellent in 8 (11%), good in 20 (28%), fair in 16 (23%), and poor in 27 (38%). Twenty patients had had a second operation. The results were worse in patients with Outerbridge grade III-IV cartilage damage. Since the clinical results deteriorated with time, this surgical procedure should no longer be used to treat patients with patello femoral pain syndrome. PMID- 1622708 TI - Training in basic microsurgical techniques without experiments involving animals. AB - Until recently, anaesthetised rats have been the usual material employed for learning basic microvascular and microneurosurgical techniques. However, ethical considerations, the costs involved and legislation controlling experiments with animals allow training in microsurgery for extended periods of time at a few medical centres only. This paper reports on our experience of an alternative training programme largely conducted without using live animals. As the basic material we selected legs of slaughtered pigs. According to the developing skill of the trainee, basic microsurgical techniques can be practised on arteries and veins of various sizes in these legs. To verify positive results, the vessels are subsequently perfused with human blood under pressure. The model described is particularly suited to the acquiring of skills in microneurosurgery. Mono-, oligo and polyfascicular nerves, structurally similar to the configurations found in human extremities, are found in pig legs. The ever-increasing importance of microsurgery in modern medicine requires more and more surgeons and orthopaedists to familiarize themselves with these techniques. The model we propose for teaching and training substantially facilitate such further professional training in an efficient way, and at the same time allows a substantial reduction in the number of experiments conducted on animals. PMID- 1622709 TI - Three-dimensional kinematics of total knee replacement systems. AB - In an in vitro study we collected data relating to three-dimensional kinematics and stability patterns in 40 knee joint specimens. The specimens were tested in an apparatus: the femur was flexed on a fixed transverse axis, while a freely mobile tibial assembly allowed measurement of all passive translational and rotational movements. Translational forces, torques and compression forces were introduced and the results compared with the measurements taken after implantation of different arthroplasty devices. This study compares the kinematics of a knee with mobile meniscal bearings (low contact stress, LCS) with the data relating to a more constrained system (Tricon M). The LCS knee showed the better kinematic behavior compared to the natural knee. PMID- 1622710 TI - Complications of high tibial osteotomy and internal fixation with staples. AB - Osteotomy for osteoarthritis of the knee has established itself well since its first description by Jackson and Waugh [8, 9]. Internal fixation with staples allows early functional treatment with only a minimum of operative intervention. Removal of the metal is optional. In the 5-year period from 1986 to 1990, 182 high tibial osteotomies were performed at the Orthopaedic Department of the University Hospital of Freiburg. In four cases internal fixation was done with plates; in 178 cases two or more staples were used; in 3 cases a screw was additionally inserted for better hold. The staples became loose intraoperatively in eight cases (4.5%); only once did a dislocated staple have to be reoperated on post-operatively. Further complications which are independent of the method of internal fixation are summarized in the article. Complications of surgery on the long bones of the leg are inevitable, but with only one postoperatively dislocated staple and one case of non-infected pseudarthrosis (i.e. a method related complication rate of 1.1%), internal fixation with staples for high tibial osteotomy presents itself as a reliable and safe procedure. PMID- 1622711 TI - Physiopathology of the knee joint after distal iliotibial band transfer. AB - In an experimental study of 14 cadaver knee joints, the pressure load on the joint surface after distal iliotibial band transfer was measured using Fuji Prescale foils. With an intact anterior cruciate ligament, increases of up to 153% for the average pressure load and of 225% for the total pressure in the lateral compartment were found in relation to the fixation point chosen. At point P3--slightly dorsal to the insertion of the lateral collateral ligament--the area loaded with maximum pressure increased to six-fold. Fixation at the transition of the lateral femoral condyle to the femoral shaft at the start of the linea aspera was associated with the least pressure increases in both the lateral and the medial compartments. Under all experimental conditions, lateral extra-articular stabilization with fixation at the insertion of the fibular collateral ligament was shown to be associated with significantly higher load increases. While a shift of pressure load to the dorsal third was seen in the lateral compartment, the mid-third remained the focus of the pressure load in the medial compartment. After transection of the anterior cruciate ligament and iliotibial band transfer at the "over-the-top" point, a significant shift of pressure towards the medial compartment was seen, while the lateral pressure load decreased. Medially, the area loaded with peak pressure remained constant, while the corresponding area in the lateral joint space showed a highly significant decrease to nearly one-third of normal. After additional bilateral meniscectomy this tendency was even more pronounced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1622712 TI - The transgluteal approaches to the hip. AB - The transgluteal approach to the hip, first described by Bauer et al. in 1979, has since become a recognized routine method. Its longitudinal incision of the fibers of the gluteus medius and minimus and the vastus lateralis muscles takes advantage of the tendinous junction of these muscles over the greater trochanter. This paper describes the modifications of the transgluteal approach described in the literature and compares them to the original procedure. In 52 hip specimens, including attached muscles, the insertions and different variations of the junction of the gluteus medius, minimus and vastus lateralis muscles over the greater trochanter are described and statistically analysed. In 59.6% of all specimens there proved to be a united tendinous junction of all the muscles referred to above, while in 40.4% autonomous insertions of the gluteus medius and/or gluteus minimus were seen. In accordance with the anatomical results, the form of incision described by the original authors can be considered the most favourable. In roughly one-third of all hip operations, autonomous insertions of gluteus medius and minimus must be taken into account, since otherwise total or partial upward displacement of the autonomous muscle insertions could occur. PMID- 1622713 TI - Non-invasive treatment of long-bone pseudarthrosis by shock waves (ESWL). AB - Non-invasive treatment of non-union of diaphyses by application of the shock waves known from lithotripsy has proved successful in three out of four cases. Two thousand shock waves with a single-wave energy of 18 kV were applied by the MFL 5000 and HM3 Lithotripters of the Dornier Medizintechnik Company with manual detection of the lesion. The shock waves induced a kind of callus formation in the non-union soft tissue within about 6 weeks, which was successfully maintained and transformed into bony union in all cases but one by dynamic fixation less rigid than a plaster cast. Four cases are documented and the effects of the shock waves and principles of bony union discussed. PMID- 1622714 TI - Relationship between the pivot shift and the configuration of the lateral tibial plateau. AB - Twenty patients with a chronic anterior cruciate ligament tear were studied. First they were interviewed on the preoperative history of unexpected giving way (pivot shift), then they were tested for clinical pivot shift sign, and last, the configuration of the lateral tibial plateau was studied using magnetic resonance imaging. A connection could be noticed between the history of instability symptoms and the pivot shift sign at clinical examination (P less than 0.001). Interestingly, there was also a link between the instability history and the configuration of the lateral tibial plateau (P = 0.0021), and, further, between the clinical pivot shift sign and the configuration of the lateral tibial plateau (P = 0.0002). The variation in the shape of the convexity of the lateral tibial plateau seems to be associated with the symptoms and prognosis of the patients with rupture of the anterior cruciate ligament. PMID- 1622715 TI - Radiographic assessment of cup migration in bipolar hip arthroplasty: intra observer and interobserver errors and tolerance limits. AB - Statistical methods were used to calculate the possible observer error in measuring cup migration in bipolar hip arthroplasty from follow-up radiographs. Finding the "tolerance limits" by such methods helped in assigning the true significance of any observed change. PMID- 1622716 TI - Treatment of femoral supracondylar unstable comminuted fractures. Comparisons between plating and Grosse-Kempf interlocking nailing techniques. AB - A prospective study was done of 66 consecutive unstable comminuted supracondylar femoral fractures in adults, fixed with either plates (28 cases) or Grosse-Kempf interlocking nails (38 cases). Patients were followed up for at least 1 year (average 44 months). Interlocking nails led to a higher union rate and more satisfactory functional results. Nevertheless, the first distal transverse screw hole took a potential risk of breakage due to stress concentration. The authors conclude that for a cooperative patient, a closed static interlocking nail with strict non-weight-bearing should be the treatment of choice, and for an uncooperative patient, a closed static interlocking nail should be supplemented with a cast brace to reduce the complication rate. PMID- 1622717 TI - Intra-articular injections and articular cartilage metabolism. An experimental study in rabbits. AB - We studied the effects of repeated intra-articular injections of sterile 140 mM NaCl solution on articular cartilage in adult rabbits. After 20 injections into the knee joints over a period of 4 weeks, chondrocyte glucosaminoglycan synthesis was evenly reduced in all cartilage layers, accompanied by a significant proteoglycan depletion of the matrix which was most marked in the superficial half of the cartilage. These and other changes only partially reversed during a further 4-week period after the injections had been stopped. Our data underline the need for a clear-cut indication for intra-articular injections. The microtrauma caused by injection, in conjunction with the introduction of a carrier solution into the joint, may, at least when repeated at short intervals, lead to measurable damage to the articular cartilage. PMID- 1622718 TI - Bilateral thoracic outlet syndrome with bilateral radial tunnel syndrome: a double-crush phenomenon. Case report. AB - A case of bilateral thoracic outlet syndrome combined with bilateral radial tunnel syndrome is reported. Persisting complaints in the upper extremities after bilateral first-rib resection and scalenotomy were due to radial nerve entrapment in the radial tunnel. Although this bilateral double-crush phenomenon is extremely rare, and has not been reported previously, persistence of symptoms after initial treatment of a nerve entrapment is an indication to search for another site of compression. PMID- 1622719 TI - Irreducible palmar epiphyseal fracture-dislocation of the distal interphalangeal joint of a finger. AB - A case of irreducible palmar epiphyseal fracture-dislocation of the distal interphalangeal joint is reported. The intact collateral ligaments and flexor digitorum profundus tendon did not permit adequate distraction of the joint, thereby preventing reduction of a displaced epiphyseal fracture. PMID- 1622720 TI - S. Suzuki et al.: Ultrasound diagnosis of pathology of the anterior and posterior cruciate ligaments of the knee joint. PMID- 1622721 TI - Neuronurses bask in certification glory--can Canadian nursing afford the growing demands? PMID- 1622722 TI - Providing hemodialysis to a schizophrenic patient--an ethical dilemma. PMID- 1622723 TI - Standardized teaching plans: the best way to document patient teaching. PMID- 1622724 TI - Inadequate funding of r-HuEPO treatment for anemia in dialysis patients. PMID- 1622725 TI - Perfusion and mechanical analysis with technetium-99m 2-methoxy-isobutyl isonitrile in a case of dilated cardiomyopathy. AB - With technetium-99m 2-methoxy-isobutyl-isonitrile (99mTc-MIBI), regional wall thickening in a patient with dilated cardiomyopathy was analyzed by the first component Fourier method. The regional wall thickening was compared with thallium 201 and 99mTc-MIBI SPECT imaging. Thallium-201 SPECT images showed mildly reduced perfusion in the posterior wall and redistribution in the septum, whereas 99mTc MIBI images showed heterogeneous accumulation around the left ventricular circumference. By means of phase analysis, diffusely decreased wall thickening and discontinuity of percent wall thickening in neighboring segments were observed throughout the left ventricle. Regional wall motion and wall thickening correlated roughly. However, discrepancies between the mechanical function and myocardial perfusion, and discrepancies in regional myocardial perfusion between thallium-201 and 99mTc-MIBI were observed. PMID- 1622726 TI - Transient thyrotoxicosis in a patient with a functioning nodule; a possible occurrence of silent thyroiditis. AB - A 48-year-old woman with diffuse goiter presented with typical symptoms and signs of thyrotoxicosis. Thyroid scanning with I-123 revealed a localized accumulation of the radionuclide in the left lobe which corresponded to a small nodule later detected by ultrasonography, with suppression of the remaining tissues. Owing to the overall reduced radioactivity in the thyroid, she was suspected of having silent thyroiditis causing thyrotoxicosis. Meanwhile, the thyrotoxicosis subsided concurrently with an increase in radioactivity in the extranodular area that had initially been suppressed. The histology of thyroid tissues obtained at the time of operation revealed follicular adenoma or hyperplasia in the area of the localized I-123 uptake and findings similar to those in Hashimoto's thyroiditis in the remaining tissues, supporting our clinical diagnosis of silent thyroiditis together with a functioning nodule. PMID- 1622728 TI - Serum thymidine kinase, a possible marker for monitoring the effect of bone marrow transplant treatment in early recovery phase. AB - We measured serum thymidine kinase (TK) activity with a radioenzyme assay system employing [I-125]-iododeoxyuridine as the tracer on serial specimens from five bone marrow transplant (BMT) patients before and after transplantation. The serum level of TK activity in the 4 patients with effective BMT treatment ranged from 3.0 to 16.9 U/L (mean, 7.80 U/L) before transplantation and from 27.3 to 236.1 U/L (mean, 82.95 U/L) after the BMT treatment. Mean serum TK activity increased 13.17-fold (range, 1.68 to 29.14-fold). In contrast, the activity in the patient with ineffective BMT treatment was not significantly different during, before, or after BMT treatment. In addition, serum TK activity in BMT patients was well correlated with the change in the number of leukocytes before and after BMT treatment [r = +0.709 (p less than 0.01), y = 0.012 x +0.87]. We conclude that the determination of serum TK activity in BMT patients is very useful in monitoring the course of bone marrow transplantation in the early recovery phase. PMID- 1622729 TI - Esophageal clearance scintigraphy, in diabetic patients--a preliminary study. AB - The aim of this preliminary study was to evaluate the predictive value of esophageal clearance scintigraphy (ECS) in the diagnosis of esophageal autonomic neuropathy in diabetic patients without any esophageal symptoms. A single swallow ECS was performed in 12 diabetic patients and 15 normal volunteers, and esophageal transit time (ETT) and esophageal (Es) T 1/2 values were calculated. ETT and Es T 1/2 were found to be significantly prolonged in the diabetic group (p less than 0.01 and p less than 0.05, respectively). In this preliminary study, our results strongly suggest that ECS may be an important noninvasive diagnostic tool in the evaluation of diabetic patients with asymptomatic esophageal autonomic neuropathy. PMID- 1622727 TI - Quantitative phase analysis of myocardial wall thickening by technetium-99m 2 methoxy-isobutyl-isonitrile SPECT. AB - Regional wall thickening was assessed by ECG-gated SPECT using technetium-99m 2 methoxy-isobutyl-isonitrile (99mTc-MIBI). For myocardial segments with an optimal short axis, regional count changes from end-diastole to end-systole were used to calculate the regional wall thickening. Functional images displaying amplitude, % wall thickening (% WT), and phase were generated by a fundamental Fourier analysis. In the control subjects, % WT analysis showed heterogeneous contraction among the left ventricular wall segments. The amplitude values showed a similar pattern to the %WT values. Phase images demonstrated that the timing of ventricular contraction was almost homogenous between the various wall segments. In the CAD patients, regional decreases in amplitude and %WT corresponding to zones of reduced perfusion were shown in the ischemic segments. Phase images also indicated asynchronous contraction in these segments. Phase analysis of regional wall thickening in 99mTc-MIBI scintigraphy seems to be useful for understanding regional myocardial function in combination with perfusion scanning. PMID- 1622730 TI - Demonstration of systemic lymphnodes by bone scintigraphy in amyloidosis. AB - We report a case of primary amyloidosis with calcification of systemic lymphnodes which were demonstrated as positives by bone scintigraphy. Positive sites delineated by bone scintigraphy would seem likely to reflect avid calcification of amyloid deposits. The discovery of positive systemic lymphnodes by bone scintigraphy is very rare in a routine study and may allow for amyloidosis in a differential diagnosis. PMID- 1622731 TI - SPECT demonstration of splenosis. AB - Splenosis is defined as the heterotopic autotransplantation of splenic tissue. The main cause of splenosis is splenic rupture following abdominal trauma, in which fragments of splenic tissue are seeded throughout the peritoneal cavity. Demonstration of splenosis by scintigraphy or CT imaging has been reported, but there is no previous report of simultaneous demonstration by SPECT and CT imaging. Autotransplantation of splenic tissue in the abdominal cavity forms a solid tumor-like image on CT and is difficult to differentiate from other abdominal masses. In such cases, SPECT demonstration of splenosis is very important for identification of its exact site. A case report of splenosis is presented, in which simultaneous demonstration by SPECT and CT was performed. This was confirmed at laparotomy for gastrectomy. PMID- 1622732 TI - The combined effect of lymphokine activated killer cell and radiation therapy on rat brain tumor in vitro. AB - The in vitro effect of a combined treatment with lymphokine activated killer (LAK) cell and radiation therapy on rat brain tumor was examined using 51Cr release assay. The tumor cell-line used in this experiment was 9L rat brain tumor derived from a Fischer 344 rat. LAK cells were obtained by culturing rat lymphocytes with recombinant human interleukin 2 for at least 3 days. The cytotoxic activity of the LAK cells was examined by 51Cr release assay. Irradiation was done by exposing the microtiter plate in which the 51Cr labeled 9L cells and LAK cells were cultured to a 137Cs gamma cell unit. Without irradiation, there was 18% cytotoxicity in the 1:100 tumor-to-LAK cell ratio specimen after 24 hrs cocultivation. However, if 5 Gy of irradiation was given, followed by 12 hrs incubation, the cytotoxicity was enhanced significantly at the same cell ratio (30%). This enhancement effect was the most prominent when the cell ratio was 1:100 and the irradiation dose was 5 Gy. To generate the enhancement effect, an incubation time of over 8 hrs both before and after irradiation was required. The supernatant of the LAK cells showed 19.8% and 11.4% cytotoxicity with and without irradiation, respectively. This result indicates the participation of a cytotoxic factor released from LAK cells. PMID- 1622733 TI - Immunomodulation by orally administered protein-bound polysaccharide PSK in patients with gastrointestinal cancer. AB - The present study was designed to assess the effects of the protein-bound polysaccharide PSK on the immunological status of patients with gastrointestinal cancer. Twenty-nine gastric and 18 colorectal cancer patients were randomly assigned to either the control or PSK group. Patients in the PSK group were given 3.0 g of PSK orally before surgery, either daily or every other day. Patients in the control group received no PSK. The data of peripheral blood lymphocytes (PBL) were compared before and after administration of PSK, and those of the regional node lymphocytes (RNL) were compared between the control and the PSK group. The results indicate that the effects of PSK were significantly influenced by the duration of administration, but not by the frequency of administration. In the patients belonging to the short term PSK group (administration less than 14 days), the response of the PBL to PSK and Con A become significantly stronger compared to before the administration of PSK, whereas the cytotoxicity against K562 and KATO-3, and the proportion of CD16+ cells increased significantly in those patients belonging to the long term PSK group (greater than or equal to 14 days). In addition, the proportion of CD9 + 11b + suppressor T cells decreased in the RNL of the short term PSK group, whereas the proportion of CD4 + Leu8 - helper T cells in the RNL increased in the long term PSK group. These results suggest that the oral administration of PSK leads to the suppression of suppressor cells in the RNL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1622734 TI - Antitumor effect of RBS (rice bran saccharide) on ENNG-induced carcinogenesis. AB - We examined whether orally administered RBS (rice bran saccharide), prepared from rice bran by hot water extraction, increases immunocompetence, inhibits gastrointestinal carcinogenesis with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) or shows an antitumor effect. After the administration of RBS, phytohemagglutinin (PHA)- and pokeweed mitogen (PWM)-stimulated blastogenesis of lymphocytes derived from the mesenteric lymph nodes and peripheral blood was enhanced, and the helper/suppressor T-cell ratio was elevated, and migration activity of peritoneal macrophages was also increased in rats treated continuously with ENNG. ENNG induced gastrointestinal carcinomas were observed in 43% of those administered RBS (ENNG-RBS) as compared with 88% in the control (ENNG) and 94% in the prednisolone (PRD) group (ENNG-PRD). The 12-month survival rate of rats bearing gastrointestinal cancer was 58% in the ENNG-RBS group as compared with 25% in the ENNG group and 15% in the ENNG-PRD group. RBS prevented the reduction in immunocompetence in the course of carcinogenesis, suppressed carcinogenesis, and prolonged the survival of rats with gastrointestinal cancer. Antitumor activities of RBS are thought to be a kind of host mediated action. The growth inhibition ratio of transplantable ENNG-induced cancer in Wistar rats was 42.1% in the RBS and 51.8% in the 5-FU group. Since little is known about the potent antitumor activity of alpha-glucan, it would be interesting to consider the relationship between the structure and the biological activities of polysaccharides. PMID- 1622735 TI - Human blood monocyte activation by Nocardia rubra cell wall skeleton for productions of interleukin 1 and tumor necrosis factor-alpha. AB - Human blood monocytes were obtained from peripheral blood of healthy donors by counter-flow centrifugal elutriation. Functional integrity of monocytes for production of interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) in response to Nocardia rubra cell wall skeleton (N-CWS) was examined by bioassay and enzyme immunoassay. Monocytes treated with N-CWS at more than 0.5 microgram/ml produced IL-1 and TNF-alpha extracellularly. Extracellular TNF activity appeared within 4 h, and maximally, 16 h after N-CWS stimulation, whereas longer time was needed for IL-1 activity to appear, the peak production being at 24 h. The neutralizing experiment also showed that anti TNF-alpha antibody did not affect IL-1 production by the monocytes treated with N-CWS, suggesting independency of IL-1 production of TNF-alpha. These results suggest that the therapeutic antitumor effect of N-CWS is due, in part at least, to the augmented production of these monokines. PMID- 1622736 TI - Combination therapy of radiation and Sizofiran (SPG) on the tumor growth and metastasis on squamous-cell carcinoma NR-S1 in syngeneic C3H/He mice. AB - The efficacy of Sizofiran(SPG), a highly purified beta-1,3-D-glucan from the culture broth of basidiomycetes Schizophyllum commune Fries, in combination with local irradiation was investigated using squamous-cell carcinoma NR-S1 and syngeneic hosts of C3H/He mice. NR-S1 tumor was implanted sc in the thigh of C3H/He mice. When tumor grew to 4 mm in diameter, the local irradiation of 55 Gy was delivered. SPG was injected im at a dose of 5 mg/kg. When SPG was administered after irradiation, remarkable inhibition of tumor growth was observed in comparison with the radiation alone group. Furthermore, the combination effect of radiation and active immunotherapy using mitomycin C treated NR-S1 cells as vaccine was examined. When radiotherapy and active immunotherapy were combined with SPG, suppression of tumor growth was observed from an early stage in comparison with the group which was not administered SPG. SPG also inhibited the pulmonary metastasis of NR-S1 tumor after radiotherapy. PMID- 1622737 TI - Therapeutic evaluation of interleukin-1 for stimulation of hematopoiesis in primates after autologous bone marrow transplantation. AB - A multiple dose IL-1 therapy was evaluated for its capability to stimulate hematopoiesis in normal primates and to restore hematopoiesis after autologous bone marrow transplantation. The administration of IL-1 to normal animals over a dose range of 0.5 to 10 micrograms/kg/d led to a 7-12 fold increase in peripheral blood neutrophil and monocyte counts after 24 hours. This increase in the mature peripheral blood myeloid cells was followed by changes in the myeloid composition of the bone marrow, where the percentage of myeloid elements increased along with a transient increase in myeloid progenitor cell activity. IL-1 treatment also led to an initial decrease in platelet counts of 10-30% during the first 3 days of treatment. However, a striking finding was a significant and long lasting stimulation of increased platelet production with platelet counts increasing to 77% of baseline 3 days after cessation of treatment and remaining elevated for the next 10 days. The therapeutic potential of the IL-1 regimen to restore hematopoiesis was further evaluated in an established autologous bone marrow transplantation model. In monkeys receiving IL-1 doses, 1.0 and 5.0 ug/kg/d, neutrophil counts recovered to greater than 0.5 x 10e9/1 on day 16, one day earlier than control, but the recovery to baseline neutrophil counts occurred 5 days sooner than control. IL-1 therapy had its greatest effect on the restoration of platelet counts after transplantation, reaching greater than 100 x 10e9/1 by day 21, two weeks earlier than control. This work demonstrates that IL-1 therapy stimulates myelopoiesis but its most promising clinical application is the stimulation of platelet production. PMID- 1622738 TI - Endolymphatic delivery of IL2 in patients with melanoma and lymphoma. AB - During this phase I/II study, enodolymphatic cannulae were placed in the iliac lymphatics under general anaesthesia. IL2 was then infused via this route at escalating doses until the highest tolerated dose was achieved; then, continuous infusion was maintained for 2 to 3 weeks. Seven patients with advanced cancer (3 lymphoma, 4 melanoma), resistant to all other modalities of treatment received such therapy. Most patients tolerated 4 to 5 x 10(6) u/day of IL2 for 2 to 3 weeks with less toxicity as compared to the equivalent dosage given intravenously. No severe perioperative morbidity was experienced. One melanoma patient had a minor clinical response. Changes in circulating lymphocyte numbers and cytotoxicity demonstrated a systemic effect of endolymphatic IL2 therapy. CONCLUSIONS: The endolymphatic administration of IL2 is associated with less toxicity than the intravenous route but still achieves a systemic effect; a lower tumour burden may prove more responsive to this therapy. PMID- 1622739 TI - Clinical trials of intrasplenic arterial infusion of interleukin-2 (IS-IL-2) to patients with advanced cancer. AB - We tried a infusion of interleukin-2 (IL-2) of a relatively low dose via an intrasplenic arterial catheter connected to a chronometric infusion (IS-IL-2). Eighteen patients of colorectal cancer with metastases to the liver or lung or of unresectable hepatoma received a 24 hour continuous infusion with low dose recombinant of IL-2 (mainly 8 x 10(5) JRU/day) for 25-40 days. All patients tolerated this protocol of the therapy and the main toxic effects were fever and general fatigue. Such serious toxicity as previously reported by high dose IL-2 therapy was not observed. Data of hepatic and renal functions were normal. IS-IL 2 therapy induced a high incidence of eosinophilia (12/18) and thrombocythemia (12/18). Peripheral natural killer (NK) and LAK activities were augmented in all patients and total white blood cell counts were increased during IS-IL-2 therapy. An increase in IL-2 receptor expression of peripheral blood mononuclear cells and significant rises in numbers of Leu11 (CD16)+, OKM1(CD11)+ and OKIa1(HLA-DR)+ were observed. Of 18 patients 12 were evaluable for their response to therapy. Partial response (PR) was observed in one unresectable hepatoma and 11 demonstrated no change (NC) or progressive disease (PD). Six patients were not evaluable because of additional therapy (3 cases) or decreasing tumor cell markers having no measurable lesions (3 cases). Three patients of colorectal cancer from an unresectable group were presumed to have micrometastases to the liver as suggested by an elevated serum CEA level. After receiving IS-IL-2 therapy they demonstrated a decrease in the serum CEA level for more than 3 years after treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1622740 TI - Inhibition of proliferation of retrovirus-immortalized macrophages by LPS and IFN gamma: possible autocrine down-regulation of cell growth by induction of IL1 and TNF. AB - The GG2EE macrophage tumor cell line was previously established by immortalization of C3H/HeJ mouse bone marrow cells with the J2 retrovirus which contains the v-myc and v-raf oncogenes. Studies on the control of GG2EE cell proliferation in vitro have recently been performed. We observed that the combination of 5-25 U/ml recombinant mouse interferon-gamma (rmIFN-gamma) plus 0.03-0.3 micrograms/ml lipopolysaccharide (LPS) markedly inhibited the proliferation of GG2EE cells (by greater than 95%) in vitro, while either agent alone inhibited only by less than 40% and 0-10%, respectively. Subsequent studies established that biologically active IL1-like (2-4 U/ml) and TNF alpha-like (50 100 U/ml) activities were released into the supernatants of LPS-treated GG2EE cells. The combination of IFN-gamma + LPS induced more (6-8 U/ml) IL1 release. These results suggested that the inhibition of proliferation of GG2EE cells by IFN-gamma + LPS could have been mediated in part by cytokines produced by the cells themselves. rhIL1 alpha at a concentration of 10 U/ml inhibited GG2EE proliferation by 25-30%, while rmIFN-gamma (25 U/ml) + rhIL1 alpha (10 U/ml) inhibited proliferation by 98%. Thus, 10 U/ml rhIL1 alpha could completely replace LPS in the LPS + rmIFN-gamma combination. Further, the combination of low doses of rhIL1 alpha (0.1 to 1 U/ml) plus rmTNF alpha (250 U/ml), which together inhibited proliferation by less than 20% synergized with doses of 5 to 25 U/ml rmIFN-gamma to inhibit proliferation of GG2EE cells by 98-99%. These results suggest that cytokines produced by the cells themselves can synergize with rmIFN gamma to inhibit the oncogene-driven proliferation of GG2EE cells. PMID- 1622741 TI - Effect of a 12 Hz and of a 460 Hz pulsed magnetic field on the weight of AKR mice. AB - AKR mice were exposed to a 6 mT, 12 Hz or 460 Hz pulsed magnetic field (PMF) 30 minutes twice a week. The exposure took place in utero and/or during the life span for four consecutive generations. The adult mice exposed to the 460 Hz PMF only after the birth time were lighter than the controls; for the two frequencies the decrease in weight with the ageing was less pronounced than in the controls. When the exposure took place in utero the exposed new-born mice were heavier than the controls. The difference in weight progressively disappeared when the mice were exposed to the 12 Hz PMF, persisted when the mice were exposed to the 460 Hz PMF. PMID- 1622742 TI - Treatment with tumour infiltrating lymphocytes and interleukin-2 in patients with metastatic melanoma: a pilot study. AB - Tumour infiltrating lymphocytes (TIL) were isolated and expanded from biopsy samples of 4 patients with metastatic melanoma. The patients were treated with autologous expanded TIL and continuous or bolus infusion of Interleukin 2 (IL-2) at a dose of 18 x 10(6) International Units/m2/day for 5 days starting 36-48 hours after administration of cyclophosphamide at a dose of 1 g/m2. The number of TIL infused ranged from 10(10) to 5.56 x 10(10) cells. Two patients had stable disease (SD) lasting for 2 1/2 and 4 months respectively and they died 24 and 13 months after therapy. One patient died during therapy due to a pseudomonas septicaemia and another patient developed progressive disease (PD). He died 3 months after the start of therapy. The side effects were substantial but most of them were reversible upon cessation of the treatment. The majority of the expanded TIL of all patients were of the CD8+ phenotype. Cutaneous metastases from two patients, removed after treatment with IL-2 and TIL, showed moderate lymphocytic infiltration also mainly of CD8+ T cells. The treatment with IL-2 and TIL is feasible, but further investigations should continue in an attempt to improve the efficacy of the therapy, to reduce toxicity and to diminish the costs and labour of the culture methods. PMID- 1622743 TI - Predictive indicators for the therapeutic effect of OK-432 in patients with chronic active type B hepatitis. AB - Twenty-two patients with chronic type B hepatitis were treated with OK-432. Immunological parameters were serially measured to find predictive indicators for the seroconversion from hepatitis B envelope antigen (HBe Ag) to anti-HBe. In patients who achieved the disappearance of HBe Ag associated with or without the appearance of anti-HBe, the numbers of CD8+DR+ and CD4+DR+T cells in peripheral blood increased gradually during OK-432 therapy and then reduced subsequently to the seroconversion from HBe Ag positive to anti-HBe positive. Increases of DR positive T cells in numbers were significantly correlated with increased amounts of IFN-gamma produced in response to in vitro OK-432 stimulation. In vitro OK-432 stimulated IFN-gamma production and the increase of CD8+DR+T cells in number in peripheral blood could be proposed as predictive indicators for the disappearance of HBe Ag. PMID- 1622744 TI - Hyperthermia in cancer growth regulation. AB - With present techniques, hyperthermia used alone can cause complete clinical regression in 10-15% of tumours but the duration of response is very short. The greatest advantage for hyperthermia at the present time appears to be in combination with radiation in the local control of cancer growth. Currently, large randomised phase III studies are in progress to determine whether the addition of local hyperthermia to radiation or chemotherapy yields significant advantage. Phase III studies of wholebody hyperthermia in combination with chemotherapy are planned for the future and will include tumours with a high growth fraction such as small cell lung cancer and high grade non Hodgkins lymphoma. PMID- 1622745 TI - The M20 IL-1 inhibitor prevents onset of adjuvant arthritis. AB - Cytokines, specifically IL-1 and TNF, have been implicated as important mediators of joint destruction in rheumatoid arthritis (RA). Elevated levels of IL-1 in the joint fluid of patients with RA have been reported, as well as the presence of IL 1 inhibitory activity. We have reported the characterization of an inhibitor derived from a myelomonocytic cell line cloned in our laboratory which is specific for IL-1. This IL-1 inhibitor is protein in nature which specifically inhibits activity in vitro and in vivo. Previous studies showed that the inhibitor reduced acute inflammatory reactions associated with IL-1 (fever, leukocytosis, local foot pad swelling, lymph node enlargement and acute phase reactants). Thus it was of interest to study whether the M20 IL-1 inhibitor could modify adjuvant-induced chronic inflammation in rats, which is often used as a model for human RA. Administration of complete Freund's adjuvant (CFA) into Lewis rats, resulted in a severe adjuvant arthritis (AA) which reached peak severity after 14 days. Daily administration of IL-1 inhibitor, beginning after injection of CFA, abolished the appearance of AA. The parameters investigated were: joint swelling (the increase in diameter of joints), peri-articular erythema, limping of the rats and histological examination. The effect of the M20 IL-1 inhibitor was shown to be dose dependent and the IL-1 inhibitor alone had no adverse effects. These results indicate that the M20 IL-1 inhibitor may have a role in the treatment of AA and may be used to reduce pathological processes in joint inflammation. PMID- 1622746 TI - Control of the transmission of Vibrio cholerae and other enteropathogens by foods originating from endemic areas in South America and elsewhere as a model situation. AB - The cholera-pandemic raging in South and Middle America and endemic cholera in other countries call for measures of health protection of the local population, but particularly with respect to the young, old, pregnant and immunocompromised citizens of countries importing food from the areas where the disease has struck. Instead of harshly barring importation, a more humanitarian policy is recommended, relying on assistance of areas presenting risks, with the introduction of and adherence to rigorous measures of longitudinally integrated microbiological safety assurance. This model is equally applicable to other enteric diseases transmitted by food. Examples are given of how canned foods of neutral pH, fishery products, vegetables and certain fruits should be processed for safety. Importation monitoring strategies, linked to this proactive approach to consumer protection, are briefly summarized. PMID- 1622748 TI - Efficacy of prolonged (48 h) selective enrichment for the detection of foodborne Salmonella. AB - The effect of prolonged (48 h) incubation on the productivity of five enrichment temperature conditions (tetrathionate brilliant green, 35 and 43 degrees C; Muller-Kauffman tetrathionate brilliant green, 43 degrees C; Rappaport Vassiliadis, 43 degrees C; selenite cystine, 35 degrees C) was compared to homologous results obtained under standard (24 h) conditions of selective enrichment. Of 797 high moisture and 166 low moisture foods tested, 171 (21.5%) and 80 (48.2%), respectively, were found to contain salmonellae by one or more analytical condition. Combined results of the five enrichment conditions after 24 and 48 h of incubation identified 247 (98.4%) and 250 (99.6%) of the 251 contaminated samples identified in this study. Our results are at variance with earlier reports on the greater method sensitivity with extended (greater than or equal to 48 h) periods of selective enrichment. The productivities of individual enrichment conditions after each period of incubation varied markedly where recovery rates with TBG43 and MKTBG43 exceeded that obtained with SC35 and TBG35. Our findings also underline the determinant role of enrichment at an elevated temperature (43 degrees C), and use of multiple enrichment and plating media for the optimal recovery of foodborne Salmonella. PMID- 1622747 TI - Sites of action by propionate on Listeria monocytogenes. AB - Exposure of Listeria monocytogenes to a solution of sodium propionate (8% w/v) for 60 min caused 87% of the population to be injured. Injury was evidenced by inability of the bacterium to tolerate 6% sodium chloride in tryptose agar as compared to ability to grow on tryptose agar with no added salt. Injured cells were allowed to repair in tryptose broth and the repair process was studied by addition to tryptose broth of sublethal amounts of metabolic or synthetic inhibitors. Repair of injured cells did not require electron transport or synthesis of cell wall components, mRNA or protein. No changes which may have occurred in the cell membrane of injured cells, allowed leakage of proteins or nucleotides into the medium. Exogenous cation salts enhanced the rate of recovery of injured cells. The specific activity of lactic dehydrogenase was reduced in propionate-injured L. monocytogenes. PMID- 1622749 TI - Application of predictive microbiology to assure the quality and safety of fish and fish products. AB - Predictive microbiology offers an alternative to traditional microbiological assessment of food quality and safety. The concept is that a detailed knowledge of the microbial ecology of a food product can be expressed as a mathematical model to enable objective evaluation of the effect of processing, storage and distribution operations on microbial development. Experience to date indicates the need initially to derive a mathematical model in laboratory studies, to validate the model in food products and to incorporate the information into monitoring devices. These may be chemical or physical indicators or electronic integrators or loggers. To enable a correct decision on quality or safety, it is essential that the response of the monitoring device to environmental changes mimics exactly that of the organism of concern. Most monitoring devices currently available record temperature history, but not other environmental factors that influence growth and that, in some circumstances, change during storage. The next generation of monitoring devices may be required to monitor several parameters to take full advantage of increasingly accurate and sophisticated models. PMID- 1622750 TI - Evaluation of a commercial process for collection and cooling of beef offals by a temperature function integration technique. AB - The hygienic adequacy of a commercial process for the collection and cooling of beef offals was assessed by a temperature function integration technique. The diverse operations for collection of offals were inspected. The rates of product movement through those operations, and the temperatures of products at the time of their being packed, were determined. From that information, four of the nine product types were selected for examination of their temperature histories during the assembly and cooling of the cartoned products. The products selected encompassed product at near-body and near-air-ambient temperatures at the time of packaging, product in the largest and smallest cartons used in the process, and product with relatively short and long residence times in an unchilled carton stack assembly area. Twenty-one temperature histories were collected for each of the products, and the possible proliferation of an indicator organism, Escherichia coli, calculated for each temperature history. The results were assessed against a temperature function integration criterion derived from studies of beef carcass and cartoned meat cooling processes. Products packaged at near-ambient temperature readily met with the criterion, but products packed at near-body temperatures did not comply. The latter non-compliance was extreme for product packaged in large cartons. However, the principal cause of non-compliance was identified as highly variable cooling conditions in the carton freezing facility. A brief survey of air speeds and temperatures within that facility indicated means by which product cooling could be better controlled. PMID- 1622751 TI - Headspace flavour compounds produced by yeasts and lactobacilli during fermentation of preferments and bread doughs. AB - Production of volatile flavour compounds during fermentation with pure cultures of Saccharomyces cerevisiae and Candida guilliermondii, Lactobacillus brevis and Lactobacillus plantarum have been investigated, using wheat doughs and several preferements as substrates. For yeast, preferments consisted of 10% (w/v) glucose, maltose and sucrose solutions, whereas for lactobacilli they consisted of supplemented and unsupplemented (3% and 10% (w/v)) glucose solutions, and a 10% (w/v) wheat flour slurry. Seven volatile compounds (acetaldehyde, acetone, ethyl acetate, ethanol, hexanal+isobutyl alcohol, and propanol) were detected when using yeasts. All these compounds, except propanol, appeared for all the substrates assayed, with ethanol as the predominant component. Generally, S. cerevisiae produced higher amounts of the different components than C. guilliermondii. Both yeasts produced larger amounts of volatile flavour compounds during fermentation in glucose and sucrose solutions than in maltose or wheat dough. In general the yeasts examined produced more flavour components than the lactobacilli. For the lactobacilli the highest number of volatile flavour compounds were observed for substrates containing flour. PMID- 1622752 TI - Campylobacter jejuni non-culturable coccoid cells. AB - The behaviour of Campylobacter jejuni in the environment is poorly documented. Rapid loss of viability on culture media is reported. This phenomenon is associated with the development of so-called coccoid cells. It has been suggested that these cells can be infective to animals and man. Results obtained with ATP measurements of coccoid cells and Direct Viable Count (DVC) support this hypothesis. Introduction of coccoid cells into simulated gastric, ileal and colon environments did not result in the presence of culturable cells. Oral administration to laboratory animals and volunteers caused no typical symptoms of campylobacteriosis. Until 30 days after uptake of the cells antibodies against C. jejuni could not be detected in the blood, and the presence of this microorganism in stool samples could not be demonstrated. PMID- 1622753 TI - Testing multiple variables on the growth of a mixed inoculum of Salmonella strains using gradient plates. AB - Six Salmonella strains were grown on two-dimensional sodium chloride-pH and temperature-pH gradient plates. Using image analysis the results were expressed in the form of three-dimensional wire frame graphs. On the temperature-pH gradient plates the optimum growth range was 20-30 degrees C and the minimum pH for visible growth was ca. pH 4, except for strain S. typhimurium CRA63 which grew over a narrower temperature and pH range. On the NaCl-pH gradient plates (whose NaCl gradient began at 2.75% (w/v) NaCl) the maximum concentration of salt at which growth was visible varied from 3.9% to 6.0%, and the minimum pH at which growth was observed varied from pH 4.7 to 5.4 according to the strain used. The incorporation of 0.02% (w/v) sodium nitrite reduced the maximum salt concentration and increased the minimum pH at which the strains could grow. The strains were combined and used in a mixed inoculum on NaCl-pH gradient plates containing 6 different concentrations of NaNO2 incubated at 6 different temperatures. Comparison of the data from the mixed inoculum with data from individual strains showed that, apart from one case, the mixed inoculum represented the extremes of the growth domains of the individual strains. The effect of NaNO2 on the ability of the strains to grow at different pH, NaCl concentrations and temperatures, was more clearly shown by subtracting the data of plates containing NaNO2 from the data of plates without NaNO2. PMID- 1622754 TI - The effect of resuscitation and the incubation-temperature on recovery of uninjured, heat injured and freeze injured enterococci. AB - Five strains of enterococci were inoculated on the Slanetz and Bartley enterococcus agar (EA), and incubated at 37 degrees C and 44 degrees C following: no injury, heat-injury and freeze-injury. The experiments were repeated introducing a 2 h resuscitation step in Tryptic Soy Agar (TSA) at 37 degrees C and subsequent overlay with EA (TSA/EA) followed by incubation at both 37 degrees C and 44 degrees C. The TSA/EA method gave a significantly better recovery (1% confidence level) than the EA method at both 37 degrees C and 44 degrees C. The effect of incubation-temperature was only significant for two strains of Enterococcus durans, as one strain showed no growth at 44 degrees C and the other strain was recovered significantly (5% confidence level) better at 37 degrees C that at 44 degrees C when employing the EA method. Interpretation of the results using TSA/EA method was easier than that of the EA. Different lactic streptococci and lactobacilli commonly employed in the dairy industry did not develop false positive colonies in TSA/EA incubated at 37 degrees C. PMID- 1622755 TI - Bacteriological composition of pigskin surfaces during cold storage at various degrees of relative humidity. PMID- 1622756 TI - Contamination of pig hindquarters with Staphylococcus aureus. AB - Swab specimens from 4357 pig hindquarters provided for production of cured raw ham were contaminated with Staphylococcus aureus in 22.7%. The bacterial counts for S. aureus on the rind surface of the raw, uncured ham were between 10(1) and 10(3) cfu/cm2 in 89% of the positive samples. In the remaining 11% of contaminated ham counts of 10(3) to 10(6) cfu/cm2 were determined. There were major differences in the rate of contamination between pork from different suppliers. Questioning the suppliers revealed that pork highly contaminated with S. aureus could be traced back to certain abattoirs. This suggests that the technique of slaughter, concomitant hygiene precautions and the subsequent refrigeration of the carcasses affect the contamination of the meat with staphylococci. PMID- 1622757 TI - Development and use of the HACCP concept in fish processing. PMID- 1622758 TI - Distribution and numbers of Campylobacter in newly slaughtered broiler chickens and hens. AB - If Campylobacter is present in the intestinal tract, broiler carcasses become extensively contaminated during the slaughter process. To determine the distribution and numbers of Campylobacter jejuni/coli in newly slaughtered broiler chickens and hens, a total of 100 birds from six Campylobacter-positive flocks were sampled at three Swedish processing plants. Campylobacters were isolated in 89% of neck skins, 93% of peritoneal cavity swab samples and in 75% of subcutaneous samples. Muscle samples were only very sparsely contaminated. It is likely that the feather follicles are the orifices where C. jejuni/coli is introduced into the subcutis layer. PMID- 1622760 TI - Isolation and characterization by conventional methods and genetic transformation of Psychrobacter and Acinetobacter from fresh and spoiled meat, milk and cheese. AB - Of 126 samples of fresh and spoiled meat and dairy products, 40% were positive for the presence of Moraxella-like bacteria and 64% of Acinetobacter; 279 and 466 strains, respectively, were isolated and a part of these were tested by biochemical methods and DNA transformation assays. In some cases, the Moraxellaceae in the samples examined reached considerable quantitative levels, but their percentage in the microflora was generally low. Moraxella-like bacteria were predominant in fresh meat, Acinetobacter in spoiled meat and milk. Most acinetobacters belonged to biotype lwoffii (sensu lato) and all 90 strains tested were positive for DNA transformation with an auxotrophic Acinetobacter. Moraxella like bacteria were identified as Psychrobacter immobilis in 96% of 103 transformation assays. Moraxellaceae show lipolytic activity but they are considered of low incidence in food spoilage. Only 3.7% of acinetobacters from dairy sources was able to produce ropy milk. Unlike strains from clinical isolates, psychrobacters and acinetobacters isolated from food often do not grow at 37 degrees C. PMID- 1622759 TI - Characterisation of Danish isolates of Listeria monocytogenes by multilocus enzyme electrophoresis. AB - A total of 84 strains of Listeria monocytogenes were analysed by multilocus enzyme electrophoresis at twelve enzyme loci. Eight enzyme loci were polymorphic with between 2 and 4 alleles per locus. Fourteen electrophoretic types (ETs) were identified. Among 62 human clinical isolates from Denmark, 8 different ETs were defined. Two ETs, designated ET 1 and ET 6, accounted for 77% of the human clinical isolates investigated. These ETs are identical with those responsible for several epidemics in Switzerland and in the United States. Comparison of 58 isolates of L. monocytogenes, typed by MEE, in relation to phage typing showed that phage typing was more discriminatory than MEE. The ability of MEE to distinguish between phage types of Epi-type and other phage types, however, was almost optimal. MEE typed 23 of 24 strains of Epi-type as belonging to ET 1. In contrast ET 1 was not found in 26 strains with phage types other than the Epi type. PMID- 1622761 TI - Evaluation of substrates and storage conditions for preparing and maintaining starter cultures for tempeh fermentation. AB - Heat-pasteurized cassava root, cowpeas, partially defatted peanuts, rice and soybeans were evaluated for their suitability to support growth and sporulation of the tempeh mold, Rhizopus microsporus var. oligosporus, and the oncom mold, Neurospora intermedia, at 25, 30 and 37 degrees C. The molds grew best and sporulated most luxuriantly on cassava and rice incubated at 37 degrees C. Viability of molds remained high for up to 30 weeks when dried (a(w) 0.48), powdered substrates on which the molds had been cultured, were stored at 5, 25 and 37 degrees C. Survival was best when powders were stored at 5 degrees C, although storage at 25 degrees C did not cause a marked decline in CFU/g. R. microsporus var. oligosporus starter cultures produced on rice and then stored for 20 weeks at these temperatures compared most favorably with commercial starter cultures for preparing high-quality soybean tempeh. The simple technology required to prepare these starter cultures enhances the potential for their application in developing countries where the introduction of nontraditional fermented legume foods to low-protein diets could help to ameliorate malnutrition. PMID- 1622762 TI - Purification of X-prolyl dipeptidyl aminopeptidase from Lactobacillus casei subspecies. AB - Prolyl dipeptidylaminopeptidases from two subspecies of Lactobacillus casei were purified and biochemically characterized. L. casei ssp. casei UL21 (a debittering strain) and L. casei ssp. rhamnosus UL26 (a non-debittering strain) were the source bacteria for this study. Purification of the enzymes from both the sources was effected by a gel filtration step through Sephacryl S-300 followed by ion exchange chromatography through DEAE Sephacel. This rendered an electrophoretically homogeneous enzyme preparation. The purified enzymes from both the sources showed similar temperature optimum (45 degrees C) and pH optimum (7.0). Their activity profiles on various substrates and the nature of inhibition by different inhibitors were also found to be similar, indicating that this enzyme is perhaps not significantly involved in the debittering process during the maturation of cheese. PMID- 1622763 TI - Chemical, microbial and sensory changes during the anaerobic cold storage of beef inoculated with a homofermentative Lactobacillus sp. or a Leuconostoc sp. AB - Slices of beef were inoculated with about 3.5 log cfu/cm2 of Lactobacillus sp. 93 SMRICC 235 (homofermentative) or Leuconostoc sp. 89 SMRICC 189 and stored in 5% CO2 + 95% N2 at 4 degrees C. The microbial, chemical (glucose, L-lactate, D lactate, acetate, formate, ethanol, H2S) and sensory changes of the beef slices were studied. For beef inoculated with Lactobacillus sp. 93 the flavour score started to decrease when the maximum bacterial count was reached. Leuconostoc sp. 89 caused a rapid decrease in the flavour score before reaching the maximum bacterial count. Concentrations of acetate and D-lactate increased while glucose and L-lactate decreased in beef slices inoculated with Lactobacillus sp. 93. In the presence of Leuconostoc sp. 89 ethanol and D-lactate increased while glucose decreased. Lactobacillus sp. 93 formed the highest level of H2S, and a sulphurous off-odour was noted only in the presence of this strain. D-Lactate and acetate indicated high numbers of Lactobacillus sp. 93 on the meat surface, while D lactate and ethanol indicated high numbers of Leuconostoc sp. 89. More studies are needed in order to correlate levels of D-lactate, acetate and ethanol with sensory changes. PMID- 1622764 TI - 19F NMR studies of enflurane elimination and metabolism. AB - The elimination and metabolism of enflurane, a fluorinated ether anaesthetic, was studied by 19F NMR in vivo in both rat liver and brain as well as human body fluids. In the liver of thiobarbitone-anaesthetized rats the half-life for enflurane following exposure to 0.15% (v/v) for 30 min was 76 min but this could be decreased to 39 min by pretreatment of the animals with isoniazid (0.1% in the drinking water for 7 days), an agent known to enhance enflurane metabolism. In these animals the major organic metabolite difluoromethoxy difluoroacetate (DFMDFA) was also detected by 19F NMR in vivo. This metabolite was detected along with fluoride ion in rat and human urine and plasma by high resolution 19F NMR. Human urine also contained signals from a probable DFMDFA conjugate and unexpectedly from trifluoroacetate. PMID- 1622765 TI - Assessment of magnesium concentrations by 31P NMR in vivo. AB - 31P NMR spectra obtained in vivo reveal the presence of a few reasonably well defined chemical species, namely, ATP, orthophosphate (Pi), and, in brain, phosphocreatine. The chemical shifts of these resonances respond to changes in concentrations of ions such as H+ and Mg2+ in a manner that depends on both the chemical shifts intrinsic to individual complexes and the formation or binding constants for the several complexes. Values of the appropriate formation constants are well established in the literature. We have derived estimates of the chemical shifts intrinsic to the individual complexes by analyzing high resolution spectra of solutions whose composition brackets the domain of physiological relevance. This provides information sufficient to estimate intracellular concentrations of H+ and Mg2+ from chemical shifts seen with in vivo spectra. The primary finding is an estimate of 0.3 mM for the concentration of free magnesium in human brain. Differing values are obtained from other tissues. PMID- 1622766 TI - Perfluorocarbon temperature measurements using 19F NMR. AB - Measuring the T1 of the fluorine resonances of perfluorocarbons (PFC) is a unique method for monitoring oxygen tension in vivo. However, because T1 is also temperature sensitive, error in the pO2 determination due to animal-to-animal temperature variation may arise. Pathophysiologic conditions, such as ischemia, where temperature is not known a priori may also introduce error. Thus, measuring the PFC temperature is clearly desirable in order to correct for tissue temperature variations during the pO2 determination. Because the fluorine chemical shift of various fluorinated compounds has a significant temperature dependence, we evaluated the effect of temperature on the chemical shift of the fluorine resonances of perfluorotributylamine (FTBA). A linear relationship was found between chemical shift and temperature in vitro. In addition, the relative FTBA chemical shifts were essentially independent of pO2. Chemical shift temperature measurements in vivo, obtained from a 10 microL FTBA bubble in the preretinal vitreous space of the rabbit eye, were in good agreement (+/- 0.5 degrees C) with thermocouple measurements from the same location. Good agreement between the NMR determined temperature and core body temperature was also found. The implication of such temperature measurements for the ultimate accuracy of the pO2 determination based on PFC T1 measurements is discussed. To the best of our knowledge, this report describes the first absolute temperature measurement in vivo by NMR. PMID- 1622767 TI - Comparison of double and zero quantum NMR editing techniques for in vivo use. AB - Several multiple quantum editing techniques for in vivo proton NMR are discussed and compared using simulated and experimental data. Extensions of these techniques for improved editing are given. Relative S/N ratios, modulation characteristics, metabolite selectivity, B0 and B1 inhomogeneity and motion effects are considered. Frequency selective read pulses can be used for signal enhancement and lipid suppression. Extra suppression of undesired signals can be obtained with a two-shot t1 cycle which gives good results for both the zero and double quantum sequences. These sequences give at most 50% signal intensity and lipid suppression factors of ca 2000 and 7000, respectively. A sequence which selects zero and double quantum coherences yields 100% signal intensity but only gives a good lipid suppression factor (7000) in combination with phase cycling. It is shown that the multiple quantum modulation can be used to obtain specific metabolite editing. Corrections can be made for the effects of B0 inhomogeneity on the multiple quantum coherences; B1 inhomogeneity affects the investigated multiple quantum sequences in about the same way and decreases the volume of interest. In vivo measurements show the good performance of the proposed zero and double quantum sequences for lactate. PMID- 1622768 TI - Quantitative magnetic resonance spectroscopy by optimized numerical curve fitting. AB - A technique is reported for generating the quantitative area under selected peaks within a 31P NMR spectrum. A numerical iterative method generates the fitted curve so as to minimize the RMS deviation between the fit and the experimental data. The curve is constructed from elemental grains of spectral density ('spexels'), each of which represents an elemental Lorentzian distribution, where the centre frequency and line width of the spexel may be varied within predetermined limits. This provides a fit that in principle is not restricted to a Lorentzian model. The method allows peak areas to be estimated, including the case of overlapping peaks. The method has been tested using simulated spectra containing six overlapping spectral lines each of known amplitude (ranging from 367 to 661 mV) and area; together with additional Gaussian noise with a standard deviation ranging from 30 to 646 mV. The results of fitting both unfiltered and filtered spectra were compared. The variation of quality of fit with spectral noise and filtering has been evaluated. In all cases, the method fitted the peak amplitudes to within 1% of the simulated value. The optimization processes provide an excellent non-linear spectrum filtering algorithm. Provided the noise in the spectra did not exceed ca 400 mV, prefiltered data could be adequately fitted. PMID- 1622769 TI - A two-point volume localized T1 measurement sequence for in vivo spectroscopy using a surface coil. AB - A technique for obtaining T1 values from well localized regions using surface coils and with a clinically practicable measurement time is described. The method uses a two-point Inversion-Recovery/Saturation-Recovery (IR/SR) sequence in conjunction with the image-selected in vivo spectroscopy localization scheme. T1 values are obtained by comparing the ratio of peak areas with those in a pre computed look-up table. The method was tested by measuring the T1s of six calibrated water phantoms doped with different concentrations of gadolinium. This indicated an accuracy of 3% for T1 values in the range 400-1500 ms. 31P spectra and T1 values of Pi, phosphocreatine and alpha-, beta- and gamma-NTP metabolites from the calf muscle of healthy volunteers were obtained with the sequence employing beta 1-insensitive excitation pulses and a surface coil. The T1 values fall within the range of published values obtained by other techniques. PMID- 1622770 TI - Rabies. Oral immunization of foxes in Europe. PMID- 1622772 TI - Migration and health. Immigrant suicide rates: a comparative study. PMID- 1622771 TI - Suicide attempts. PMID- 1622773 TI - Rubella. Winter outbreak in the Australian Capital Territory (ACT). PMID- 1622774 TI - Magnetization transfer contrast in magnetic resonance imaging. AB - Magnetization transfer contrast (MTC) in magnetic resonance imaging (MRI) is the result of selectively observing the interaction of bulk water protons with the protons contained in macromolecules of a tissue. Since different tissues have different macromolecular compositions, the MTC can generate very high tissue contrast that is based on well-defined physiochemical properties. This is accomplished by combining a saturation transfer technique with standard MRI procedures. The specific practical and theoretical aspects of saturation transfer as it applies to the generation of MTC are reviewed and discussed. In the last 3 years, MTC has been applied to the study of the body, with useful applications demonstrated in evaluating the morphology of the knee joint, eye, brain, breast, and heart. The application of MTC to accentuate MR angiography and contrast agent studies has also been demonstrated. Thus, MTC is becoming another tool towards maximizing the quality and diagnostic potential of MRI. Recent studies on isolated macromolecules have suggested that the MTC effect is specific to the surface chemistry and correlation time of the macromolecules. These latter results indicate that the magnetization transfer process may provide a unique quantitative method of MR tissue characterization based on macromolecule dynamics and chemistry. PMID- 1622775 TI - Magnetic resonance imaging of the wrist. AB - Magnetic resonance (MR) imaging has developed rapidly as a diagnostic tool in the evaluation of the wrist. In this article, the authors review simple high resolution technique and appropriate surface coils to aid in wrist evaluation. Evaluation of the wrist is facilitated by an understanding of the anatomy of the carpal ligaments, the triangular fibrocartilage, and the carpal tunnel, and the anatomic features of the distal radioulnar joint. Triangular fibrocartilage tears, which represent an important cause of ulnar wrist pain, are well evaluated on MR. These appear as a linear band of increased signal on the short repetition time/echo time (TR/TE), proton density weighted spin echo, or gradient echo images. True tears should be differentiated from degenerative changes, which do not demonstrate increase in signal on T2 or T2* weighted images. With good technique, accuracies approaching 90% have been reported. MR is also useful in evaluating injuries of the interosseous ligaments and volar and dorsal radiocarpal ligaments and distal radioulnar joint instability. MR also has a role in evaluating the carpal tunnel syndrome. This is especially true with patients for whom symptoms suggest the diagnosis of carpal tunnel syndrome but for whom few objective findings exist. Findings suggestive of carpal tunnel syndrome include diffuse swelling of the median nerve, flattening of the median nerve at the level of the hamate, and increased signal of the median nerve on the long TR/TE images. MR is also indicated in avascular necrosis of the carpal bones and occult carpal fractures. MR is useful in evaluating bone tumors, particularly with regard to their extent. With the advent of more rapid scanning techniques, kinematic studies are feasible. For these, fast gradient echo techniques are employed and serial images are acquired during radial and ulnar deviation. These images may be helpful in observing integrity of intercarpal ligaments and evaluating dynamic instability. With proper attention to technique, and an understanding of wrist pathophysiology, MR is a valuable diagnostic tool. PMID- 1622776 TI - Magnetic resonance imaging of the foot and ankle. AB - Technical considerations for the magnetic resonance imaging of the foot and ankle are discussed, including the selection of the appropriate surface coil, the importance of stabilizing the anatomic region, and the principles guiding the choice of pulse sequences. The anatomy of the foot and ankle are reviewed, and the normal appearance and important variations of the different structures on magnetic resonance images are discussed. Pathology of the foot and ankle are then discussed. Topics covered include osteochondral and radiographically occult fractures, tears and inflammation of the Achilles and posterior tibial tendons, tears of the lateral collateral ligaments and sinus tarsi syndrome, primary tumors (in particular, those of the foot), synovial diseases such as pigmented villonodular synovitis, congenital abnormalities, and disorders such as tarsal tunnel syndrome and plantar fasciitis. PMID- 1622777 TI - Mental health: living in two worlds. PMID- 1622778 TI - Learning is for life. PMID- 1622779 TI - Health Visitors' Association: thriving on challenge. PMID- 1622780 TI - IV drugs: assessing pupils in Botswana. AB - This small study set out to establish the abilities of a group of pupil nurses in a rural hospital in Botswana to accurately calculate intravenous driprates and drug dosages, and how targeted teaching could improve their performance. Thirteen pupils were asked to complete a seven-item questionnaire comprising set questions on intravenous therapy, then take a second questionnaire after receiving targeted teaching. Comparison revealed that two specific problems, related to dripsets and dilutent displacement, remained after teaching, but that improvements in scores in the 'incorrect with little immediate risk' and 'correct' categories had been achieved. The author suggests that formal testing and targeted teaching are appropriate methods of helping pupil nurses evaluate and improve their skills and knowledge base. PMID- 1622781 TI - Developing nurse and midwife teachers. PMID- 1622782 TI - Complementary therapy: using music in hospital settings. AB - The therapeutic use of music in hospitals has been explored within the context of highly specific situations. Here, the author explores the place of music in improving the general ambience of the clinical scene, and investigates the sometimes conflicting results from research into its physiological benefits to patients. Music in hospitals, he argues, is an area ripe for further exploration. PMID- 1622783 TI - Vivisection: points of view. PMID- 1622784 TI - Empathy: relative nursing care. PMID- 1622785 TI - Living-in: this abode's not well. PMID- 1622786 TI - Practice: soup nurse or supernurse? PMID- 1622787 TI - A day in the life--who was that caped person? PMID- 1622788 TI - Informed consent: New formula Zealand. PMID- 1622789 TI - Education: mixed-ability tutors. PMID- 1622790 TI - Little chance of HIV from health workers. PMID- 1622791 TI - UKCC: new statement launched on HIV/AIDS. PMID- 1622792 TI - Heart health (continuing nursing education). PMID- 1622793 TI - Assessing elderly people (continuing nursing education). AB - Community nurses are increasingly likely to be involved in assessing the health status of elderly people in a number of care settings. It is important that the assessment is relevant and useful, not only for the primary health care team, but also for the elderly person and any involved carers. PMID- 1622794 TI - Quality assurance. Winning support. PMID- 1622795 TI - Quality assurance. Stateside standards. PMID- 1622796 TI - Quality assurance. Homing in on quality care. PMID- 1622797 TI - Quality assurance. Working towards change. PMID- 1622798 TI - Escape from riot zone. PMID- 1622799 TI - Secure environments: out of the dark age. PMID- 1622800 TI - Information technology: implementing a nurse information system. AB - This article explains the remit of a specially designated project nurse in preparing for the implementation of a nurse information system. The main components of a system--rostering/staff planning, workload/dependency levels and care planning--are defined and the project nurse's role in educating ward-based staff is described. The key to successful management of the necessary changes, the author argues, is adopting a 'bottom-up' approach to implementation in which nurses are encouraged to develop a sense of ownership of the selected system. PMID- 1622801 TI - Malignant disease of the prostate gland. AB - The incidence of prostate cancer is rising in the West, but information about developing treatment options and nursing care is limited. The author examines early disease detection and treatment, and discusses care for patients with locally advanced disease. The need for emotional support for sufferers and their families is stressed, and the importance of good patient education is highlighted. PMID- 1622802 TI - The role of the nurse in rehabilitation. AB - Although nurses make a valuable contribution to the process of rehabilitation, the parameters of that contribution have yet to be defined. This article describes a small study, undertaken on a care of elderly people ward, designed to elicit nurses' understanding of their role in rehabilitation. Interdisciplinary relations and patient care, the authors conclude, would be improved if nurses were taught, and developed the confidence, to implement rehabilitation techniques in practice. PMID- 1622803 TI - Nurse mobility and employment patterns. AB - There are a number of answers to the question 'what happened to nursing shortages?', says James Buchan in his regular monthly column. PMID- 1622804 TI - Managing mass casualties in Israel. AB - The author relates her experiences as an observer at an Israeli mass casualty simulated exercise in a general hospital. Israeli people, who have seen their country engaged in several major wars over the last 40 years and who live with the potential for terrorist atrocity as a daily threat, treat such exercises with great seriousness. The scale and realistic nature of the exercise was impressive, and while such activities may not be directly translatable to a British situation, the energy, commitment and systematic approach of the Israeli personnel are qualities which British hospital and military staff could adopt. PMID- 1622805 TI - Guidelines on staff with HIV. PMID- 1622807 TI - Project 2000. Be proud of the project. PMID- 1622806 TI - Reviews must be viewed positively. PMID- 1622808 TI - Project 2000. Growing pains and gains. PMID- 1622809 TI - Mental health. Psychiatric nursing in the nineties. PMID- 1622810 TI - Mental health. Nurses responding to substance misuse. PMID- 1622811 TI - Mental health. The effectiveness of community teams. PMID- 1622812 TI - The value of nursing: invisible mending. PMID- 1622813 TI - In her own right. Interview by Charlotte Alderman. PMID- 1622814 TI - Romania: story of a lost life. PMID- 1622815 TI - Foot problems in people with diabetes. AB - People with diabetes are liable to suffer potentially disastrous foot problems, including gangrene with subsequent amputation. This article describes the risk factors, management, and ulcer-prevention methods which are essential knowledge for nurses working with this patient group. PMID- 1622816 TI - Management. Setting priorities in health: the Oregon experiment (Part 1). AB - Increasing emphasis on obtaining consumer opinion in relation to needs assessment and decision making has led to interest in this country about the Oregon experiment in the US. Despite controversies over the efficacy of such approaches, it seems likely that future emphasis will be placed on devising systematic means of gathering information about societal preferences for care. In two articles, Ann Bowling reviews the evidence from America and relates it to the ongoing changes in the British health service. Part 1 introduces the ideas behind the Oregon experiment and examines similar initiatives in the UK. PMID- 1622817 TI - Psychiatric nurses' use of working time. AB - How nurses spend their time at work is an issue increasingly under scrutiny. This small study, undertaken by a nursing development team, examined the activities of staff and patients on five admission, rehabilitation and continuing care psychiatric wards. The results, sure to stimulate debate and encourage further research, suggest nurses spend less time than might have been expected doing the job for which they were trained. PMID- 1622818 TI - Improving library services for nurses. AB - Developments in pre- and post-registration nurse education mean greater demands on library resources. This article describes a survey undertaken to elicit nurses' views on the provision of library services, and includes their suggestions for improving those services. The author suggests the demands nurses make on existing resources will, in part, shape the future of nursing libraries. PMID- 1622819 TI - Trevor Clay: the Clay column. PMID- 1622820 TI - Information technology: data day implementation. PMID- 1622821 TI - Nursing in Europe: applying French dressings. PMID- 1622822 TI - Professional status: is professionalism a con? PMID- 1622823 TI - Employment: doling out patient care. PMID- 1622824 TI - Diet and nutrition (continuing nursing education). AB - Nurses, midwives and health visitors are ideally placed to give individualised dietary advice to patients and clients. Supporting people as they try to alter their eating behaviour requires up to date knowledge of nutrition and an awareness of the process of change. PMID- 1622825 TI - Wound care (continuing education nursing). AB - Nurses have the potential for preventing wounds in many of the most vulnerable patients, and improving the quality of life for patients with wounds by applying management techniques which meet the patient's actual needs. PMID- 1622826 TI - Members demand fast action on HIV spread. PMID- 1622827 TI - Anal intercourse risk of HBV in women. PMID- 1622828 TI - Community care: raising the alarm. PMID- 1622829 TI - Community care: prepared for change? PMID- 1622830 TI - Contracting for a continence service. PMID- 1622831 TI - Management. Setting priorities in health: the Oregon experiment (Part 2). AB - Increasing emphasis on obtaining consumer opinion in relation to needs assessment and decision making has led to interest in this country about the Oregon experiment in the US. In spite of controversies over the efficacy of such approaches, it seems likely that future emphasis will be placed on devising systematic means of gathering information about societal preferences for care. In two articles, Ann Bowling reviews the evidence from America and relates it to the ongoing changes in the British health service. Part 2 examines the methods, results and controversies generated by the Oregon experiment. PMID- 1622832 TI - Gestalt therapy: theory and practice. AB - Gestalt therapy, a particular type of psychotherapy, draws on existential and various Eastern philosophies, and aims to enable the individual to seek his or her own solutions to personal problems. Literally translated as 'whole', Gestalt focuses the individual to appreciate and experience the present. This article examines the Gestalt theory and considers its application to a terminally ill client and his wife. PMID- 1622833 TI - Oncology/quality assurance: a quality system for oncology nursing. AB - The benefits of three quality monitoring systems, Monitor, Qualpacs and the Dynamic Standards Setting System are explored in relation to oncology nursing. The author concludes that the flexibility provided by the 'bottom-up' design of the Dynamic Standards Setting System is admirably suited to the needs of nurses working with cancer patients. PMID- 1622834 TI - A specialist role in patient nutrition. AB - This article explores the role of the nurse as a clinical specialist in patient nutrition. The author, who also holds the position of sister in charge of a medical ward, explains the benefits of nursing input to a multidisciplinary nutrition team with a hospital-wide remit. Research carried out by the team shows that improvements in patient care and financial savings can be made through skilled management of patient nutritional needs. PMID- 1622835 TI - General practitioner contracts do not fragment individuals' care. PMID- 1622836 TI - Working parents: turning against rotation. PMID- 1622837 TI - Nursing founders on basics. PMID- 1622838 TI - Psychiatry: European freedoms. PMID- 1622839 TI - AIDS focus. Positive at school. PMID- 1622840 TI - AIDS focus. The South African dimension to caring. PMID- 1622841 TI - Differential metastatic capacity of three AKR lymphoma variants. AB - The comprehension of tumour progression has advanced due to the use of various models, the most rewarding being probably the study of malignancy variants derived from the same tumour. In the present study the biological behaviours of three AKR lymphoma variants were compared. The three variants, TAU-33, TAU-38 and TAU-39, differed markedly in biological behaviour. The TAU-39 variant formed very large 'primary tumours', TAU-33 produced local growths of intermediate size, and TAU-38 formed small s.c. tumours. However, the metastatic potentials of the variants were inversely related to their ability to produce local tumours. According to various parameters (spread to organs, cachexia and mice mortality rate), the variant of highest metastatic potential was TAU-38, the one of intermediate ability TAU-33 and the TAU-39 had the least aggressive behaviour. A lack of difference in invasive capacity as well as a similar ranking of malignancy by both s.c. and i.v. inoculation indicate a differential behaviour in late metastasis phase. Tumour progression models may contribute to a better understanding of this threatening process and to testing of new treatment modalities suitable for cancer at different stages. PMID- 1622843 TI - Enzyme histochemical reactions at the demarcation line in frostbite: an experimental study on rabbits. AB - Eleven frostbites were induced on the ears of seven New Zealand White rabbits and specimens were taken from the lesion after 1, 4 and 8 hours, and from ten further frostbites on the ears of six rabbits for examination 1, 3 and 7 days later. The specimens were taken at the border between the frozen and non-frozen skin. NADH diaphorase, alkaline phosphatase and esterase were demonstrated histochemically in the sample, which was also studied by haematoxylin and eosin staining. Five ears served as controls. Some granulocytes could be seen accumulating in the vessels and in the dermis at the border of the frostbite area after only 1 hour, and other enzyme rich cells (macrophages) also began to appear. After 4 hours the inflammation was quite obvious with the enzyme reactions clearly observable in the sections. After 8 hours there was no marked difference compared with the 4 hour picture. It was only after 3 days that the line of demarcation between the normal and frostbite tissue could be seen clearly. This was oblique in some specimens and vertical in others. The degeneration in the lesion could best be demonstrated by the NADH-diaphorase and esterase reactions and the early inflammation by the alkaline phosphatase reaction. PMID- 1622842 TI - Acute serum sickness in normal and C6 deficient rabbits: role of membrane attack complex. AB - Acute serum sickness was induced in New Zealand White (NZW) and in C6 deficient (C6D) rabbits, to compare the histology, immunofluorescence, especially distribution of poly C9 (MAC), and electron microscopic characteristics of the disease in each strain. Glomerulonephritis and albuminuria of comparable extent occurred in 13/17 NZW and 4/8 C6D rabbits. In NZW rabbits with albuminuria an early intense glomerular infiltration by mononuclear cells was associated with focal small fine granular glomerular basement membrane (GBM) deposits of IgG and BSA and more diffuse and larger deposits of C3 and MAC. After the disappearance of monocytes and decrease in mesangial cell proliferation, development of large subepithelial GBM deposits rich in all immune reactants was observed in NZB rabbits. In C6D rabbits with albuminuria a similar monocytic infiltrate occurred, but no association with IgG and C3 GBM immune deposits was noted. No deposits of MAC and no large subepithelial GBM 'humps' were observed in C6D rabbits. We conclude that the exudative (monocytic) phase of glomerular injury and albuminuria in acute serum sickness nephritis are not dependent upon terminal complement components, but the subsequent formation of large subepithelial GBM deposits does not occur in this model in the absence of MAC. PMID- 1622844 TI - Lung protein leakage in respiratory failure induced by a hybridoma making monoclonal antibody to the hydrophobic surfactant-associated polypeptide SP-B. AB - Adult mice were inoculated intraperitoneally with a hybridoma (8B5E) making monoclonal antibody to the porcine surfactant-associated polypeptide SP-B; this antibody cross-reacts with the corresponding polypeptide in the mouse surfactant system. Respiratory failure, developing 7-9 days after inoculation, was associated with a decrease in lung-thorax compliance determined during artificial ventilation, and an increase in the amount of protein including the specific antibody in lung lavage fluid. There was a statistically significant negative correlation between the compliance and the amount of protein as well as antibody recovered by lung lavage: r (log scale) = -0.69 and -0.82, respectively (P less than 0.01, both), but no decrease in the amount of phospholipids in lung lavage from animals inoculated with the hybridoma. Treatment with a large dose of porcine surfactant (about 320 mg phospholipids/kg body weight) had no positive effect on lung-thorax compliance during artificial ventilation; on the contrary, surfactant-treated animals showed a decrease in compliance similar to that seen in control animals after instillation of a similar volume of saline into the airways. We conclude that respiratory failure developing after inoculation with this hybridoma is probably at least in part mediated by flooding of the airspaces with antibody interfering with surfactant function. PMID- 1622845 TI - Effects of microbial stimulation on the number, size and activity of bronchus associated lymphoid tissue (BALT) structures in the pig. AB - The development of bronchus-associated lymphoid tissue (BALT) was investigated in the pig, which is a species in which BALT is not found constantly. Different routes of contact with a specifically lung-pathogen bacterium Actinobacillus (Haemophilus) pleuropneumoniae were tested. Pigs, selected by bacteriological screening methods and the number of granulocytes in the bronchoalveolar lavage (BAL), were infected by aerosol. They were compared to previously enterally immunized pigs using active and inactivated bacteria. The development of BALT after the infection was compared to that in pigs with a single enteral, or no, contact with the bacterium. BALT was less frequent in these groups than in the infected pigs. Previously immunized pigs developed the highest number and the largest BALT with the most prominent morphological signs of activation. Immunization with living or inactivated bacteria did not cause histological differences. BALT was preferentially located around bronchioli and small bronchi. Additional BALT predominantly occurred in the walls of larger bronchi. Definite compartments of T and B lymphocytes were not found in immunohistological studies of BALT. It was concluded that the development of BALT can be induced by different modes of microbial stimulation. PMID- 1622846 TI - Epithelial-mesenchymal interactions in experimental oral mucosal carcinogenesis: establishing a technique. AB - The carcinogen 4-nitroquinoline-1-oxide was applied to the palatal mucosa of rats for varying periods of time. This tissue was separated into epithelial and connective components and then recombined in various combinations and implanted into hypothymic mice. Seventy-two per cent of the implants were recovered and were suitable for detailed histological analysis. The technique provides a suitable model for the assessment of epithelial-connective tissue interactions in experimental oral mucosal carcinogenesis. PMID- 1622847 TI - Chronic rejection of rat renal allograft. III. Ultrastructure of vascular and glomerular changes. AB - The main histological features for 'chronic' rejection of rat renal allograft are ongoing perivascular and interstitial inflammation, vascular intimal hyperplasia and glomerular sclerosis. In this communication we have investigated the ultrastructural features of renal parenchyma by comparing chronically rejecting rat renal allografts immunosuppressed initially with cyclosporine to similarly immunosuppressed syngeneic transplants. Electron microscopy confirmed that the primary arterial change was smooth muscle cell proliferation in media, thickening and focal destruction of the internal elastic lamina, and influx of smooth muscle cells and their proliferation in the intima, leading to a nearly complete occlusion of the lumen. In the glomeruli, the most prominent features were mesangial matrix increase, narrowing of capillary lumen, and basement membrane thickening with a double contour appearance in capillary walls. A thin membrane, similar to lamina densa, appeared beneath the endothelium in some segments. Mesangial interposition, formation of new basement membrane and mesangial widening due to increase of basement membrane-like material was nearly always present. As none of these vascular and glomerular changes were observed in similarly immunosuppressed syngeneic transplants, we consider these ultrastructural alterations characteristic for chronic rejection in a rat renal allograft. PMID- 1622848 TI - Present trends on osteosarcoma and adult soft tissue sarcomas. PMID- 1622849 TI - Postoperative radiation therapy for adult soft tissue sarcomas: a retrospective study. AB - From 1977 to 1988, 81 adult patients with localized soft tissue sarcomas at different sites received postoperative external beam radiotherapy (55 Gy median dose) following primary conservative surgery. Sixty were new referrals after primary surgery and 21 were irradiated after excision of recurrent disease. With a median follow-up of 4 years (range: 2-13) the 5-year overall survival (Kaplan Meier) and local control were 55.5% and 56% respectively, while 5-year disease free survival is 49%. There were 26 (32%) local relapses and 22 (27%) distant failures. Local recurrence was the sole pattern of failure in 16 patients (20%). Functional and cosmetic results were good to excellent in most cases. In our series local control is the main prognostic variable influencing survival (P less than 0.0001), and its probability seems to show a link with the type of surgical procedure, with a trend (P less than 0.13) in favor of wide total excision. Postoperative radiation therapy represents an acceptable treatment strategy for ASTS, but further improvements are expected from future controlled clinical trials, aiming at the achievement of the definitive cure of these tumors. PMID- 1622850 TI - Osteosarcomas and adult soft tissue sarcomas: is there a place for high LET radiation therapy? AB - The treatment policy for non-operable or unresectable osteosarcoma and adult soft tissue sarcoma remains unclear or controversial, despite the progress achieved in multimodality treatments. The poor results obtained by radiotherapy alone led to consider these tumours as radioresistant and to use high Linear Energy Transfer (LET) particles, such as neutrons. These particles benefit from a higher Relative Biological Efficiency (RBE) and other biological properties tending to decrease radioresistance phenomenas. From the non randomized studies previously published, neutron-therapy seems to give better local control rates, compared to photons and/or electrons. But these results are not strongly convincing, due to the large heterogeneities in patient recruitment, histological types, sizes, sites and moreover to the high complication rates encountered in some studies, even if they are mainly imputable to the use of low energy machines. The use of high-energy hospital-based accelerators combined to the possibilities of accurate dose distribution offered by conformal therapy, the potential value of light ion beam therapy combining the dose distribution advantages of protons to the biological properties of high LET particles, represent the directions in which progresses might be made for further improvement of non-operable or unresectable osteosarcoma and soft tissue sarcomas treatment results. PMID- 1622851 TI - Adriamycin in hyperthermic perfusion for advanced limb sarcomas. AB - From February 1989 to April 1991, 12 hyperthermic limb perfusions (HLP) with adriamycin (ADR) were performed in 12 patients with high grade soft tissue sarcomas (9 in the leg and 3 in the arm); two were at A.J.C. stage IIb, eight stage IIIb and two stage IV. ADR (0.7-1.5 mg/kg) was administered in bolus at a mean temperature of 41.5 degrees C and perfused for 60 min. No systemic toxicity was reported; seven patients had grade II locoregional toxicity, another four grade III and one grade IV. Tumor necrosis (radiological evaluation) was less than 25% in two patients, 25% to 50% in two, 50% to 75% in five and greater than 75% in three. Limb sparing surgery was feasible in ten patients. At present eight patients are alive; three had local recurrence and four distant metastases. PMID- 1622852 TI - Feasibility and efficacy of arginine 2-mercaptoethanesulfonate (ARGIMESNA) in the prevention of hemorragic cystitis from ifosfamide (IFO). AB - Tolerability and efficacy of the new uroprotective agent ARGIMESNA was assessed within a randomized cross-over study comparing it to sodiummercaptoethanesulfonate (MESNA), in patients treated with IFO. MESNA i.v., 20% of IFO dose, was given to all patients before chemotherapy; 4 h later, at random, they received ARGIMESNA p.o., 20% of IFO dose every 2 h x 4, or MESNA p.o., 40% of IFO dose every 4 h x 2. Overall, 78 cycles of oral uroprotection were administered: 37 for ARGIMESNA capsules; 41 for MESNA vials p.o. ARGIMESNA was subjectively better tolerated, determining gastro-intestinal discomfort in only 12 out of 37 cycles versus 34/41 of MESNA p.o. (p less than 0.001). Both preparations were equivalent for subjective and objective efficacy since no cycles were complicated by urinary symptoms (dysuria, stranguria, or hematuria). Nevertheless, 2 patients (7.7%) refused further oral assumption of both uroprotectors, whereas MESNA i.v. was added in other 7 patients because of nausea and vomiting caused by chemotherapy. In conclusion, this new oral preparation of mercaptoethanesulfonate turned out to be well tolerated, safe and active in the prevention of haemorrhagic cystitis from IFO. PMID- 1622853 TI - Doxorubicin (or epidoxorubicin) combined with ifosfamide in the treatment of adult advanced soft tissue sarcomas. AB - The results of the association of doxorubicin plus ifosfamide in the treatment of locally advanced and/or metastatic adult soft tissue sarcomas as reported in the literature from 1986 up to the present time are reviewed. The data confirm the effectiveness of the association doxorubicin plus ifosfamide, with an objective response rate of 33.25% (range, 22% to 42%), with 9.3% of complete responses. The highest percentages were reported in studies using doses of doxorubicin of 60 mg/m2 or higher, with a suggested dose-response correlation. The pattern is generally well tolerated, with a prevalently haematological toxicity. Results being equal, the use of epidoxorubicin seems to allow a lower incidence of high grade leukopenia, and an higher dose-intensity of the drug administered. The two randomized studies by EORTC and ECOG indicate superiority of this combination compared to doxorubicin on its own or with other polychemotherapeutic regimens containing doxorubicin, without ifosfamide. However, the actual contribution of ifosfamide deserves further investigation. The impact on long-term disease-free survival is, however, poor and median survival time ranges from 8 to 12 months in responder patients. Future studies should be aimed at increasing the dosages of the drugs without a significant increase of toxicity, by administering them in continuous infusion or by the use of growth factors. PMID- 1622854 TI - Epirubicin plus ifosfamide and dacarbazine (EID) in advanced soft tissue sarcomas. PMID- 1622855 TI - Neoadjuvant intraarterial chemotherapy of soft tissue sarcomas. AB - A group of 51 patients with extremity sarcomas of soft-tissue origin received preoperative intraarterial (i.a.) chemotherapy via a percutaneously placed catheter. Treatments were performed as a series of chemotherapy cycles, giving a total of 129, and were carried out in the form of short-term infusions consisting of doxorubicin and cisplatin, which lasted for 20-40 min. These i.a. infusions were combined with complementary methods, such as a tourniquet, occlusion infusion and chemoembolization. In 3 patients complete remission and in 21 partial remission was registered, while in 27 patients only minimal response could be achieved, although in this latter group necrosis of eight tumors proved to be of significant value. In 43 of 51 patients successful limb salvage surgery was carried out. PMID- 1622856 TI - The treatment of localized osteosarcoma of the extremities: the Italian experience. Studies of the National Research Council. PMID- 1622857 TI - Treatment of pelvic osteosarcoma. AB - Pelvic osteosarcoma is a very rare disease, with poor prognosis affecting young people. Since June 1987 we have observed 26 patients, F/M: 12/14, median age 23 years (range 14-55), 7 with lung metastases at diagnosis. Four patients underwent surgery as first line treatment; 4 patients received intravenous (i.v.) chemotherapy; eighteen out of 26 received 1-3 cycles of neoadjuvant chemotherapy consisting of high dose i.v. methotrexate plus leucovorin rescue, intraarterial cisplatin and i.v. epidoxorubicin. We obtained 8 PR, 9 SD, 1 PD. Hemipelvectomy has been performed in 4 cases (0%, 0%, 50%, 70% necrosis). The other 14 patients, judged not operable, received radiotherapy plus daily low doses of cisplatin. All patients have been treated with i.v. epidoxorubicin, ifosfamide, high dose methotrexate, cisplatin and etoposide. Two out of four patients who underwent surgery died at 17 and 18 months, 2 are alive and free of disease at 28+ and 17+ months from surgery. Among the 14 patients treated with radiotherapy, 9 died with a median survival of 18 months (5-22); 5 are alive with a median survival of 20 months (14-31). Although pelvic osteosarcoma has a limited cure rate at present, results could be improved in the future by means of earlier diagnosis and better combined treatment. PMID- 1622858 TI - Limb sparing versus amputation in osteosarcoma. Correlation between local control, surgical margins and tumor necrosis: Istituto Rizzoli experience. AB - Three hundred fifty-five patients with osteosarcoma were surgically managed at the Istituto Ortopedico Rizzoli between 1983 and 1988. Three hundred two patients performed two cycles of neoadjuvant chemotherapy according to two different protocols consecutively activated; the remaining 53 patients were immediately operated on without neoadjuvant treatment. Follow-up ranged from 19 to 88 months, with a mean of 51 months. Demolitive surgery was performed in 116 patients (33%), while conservative in 239 patients (67%). A radical margin was achieved only in patients undergoing amputations: no radical surgical margins were achieved by local resection: 174 resected patients (73%) had wide margins, while 34 (14%) had marginal margins; 20 patients had contaminated margins and 11 patients (5%) had intralesional margins. Wide or marginal margins were achieved in 208 (87%) of the patients managed by local resection. Local recurrence was identified in 24 of 355 patients (7%). Incidence of local recurrence is strictly related to surgical margin, but above all, to tumor necrosis induced by neoadjuvant chemotherapy. In fact, neoadjuvant chemotherapy makes limb salvage feasible in the majority of cases without increasing the risk of local recurrence: in the group of patients immediately operated on without neoadjuvant chemotherapy, the incidence of local recurrence is dramatically high even when the surgical margins are adequate. PMID- 1622859 TI - SARG: a new human osteosarcoma cell line. Expression of bone markers and of major histocompatibility antigens. AB - A new cell line (SARG) was established from a human radiation-induced osteosarcoma (OSA). It showed an epithelial-like morphology with polymorphous and sometimes bizarre nuclei. SARG had an osteoblastic differentiation pattern: almost 100% of the cells were positive for alkaline phosphatase, type I and III collagens and osteonectin. The expression of class I HLA antigens was detectable even after 40 in vitro passages. The expression of MHC antigens was greatly increased after in vitro treatment with interferon gamma (IFN-gamma), whereas interferon alpha (IFN-alpha) and tumor necrosis factor alpha (TNF-alpha) increased the expression of class I antigens, but not of class II antigens. SARG was tumorigenic after subcutaneous injection in nude mice. Experimental metastases were never detected. PMID- 1622860 TI - Preoperative chemotherapy for osteosarcoma with intravenous adriamycin and intra arterial cis-platinum. AB - Ninety-seven patients with primary osteosarcoma of the extremities, all age 16 or older, were treated with adriamycin, 90 mg/m2, continuous i.v. infusion over 96 h, followed by cis-platinum, 120-160 mg/m2 by intra-arterial infusion. The first 37 patients, treated from 1979-1982, had a 59% complete response rate and a 54% 5 year continuous disease free survival (CDFS). Patients with complete response had an 85% 5-year CDFS compared with 13% for patients with partial and poor response. Patients treated between 1983-1988 with an intensified regimen have a 68% complete response rate and a 69% 3-year CDFS. Those who did not achieve complete remission were switched to an alternating chemotherapy program emphasizing the use of high-dose methotrexate. Limb salvage has been accomplished in 59% of patients in the first group and 80% in patients of the second group. Preoperative chemotherapy allows informed decisions to be made in postoperative management which can influence overall cure rates. Long-term follow-up is essential before final interpretation of the data. PMID- 1622861 TI - Osteonectin in osteosarcomas: a marker for differential diagnosis and/or prognosis? AB - Seventy-five osteosarcomas at various grades of histologic differentiation were investigated for evidence of osteonectin. According to the results of the study, osteonectin was present in all osteosarcomas. An association between the intensity of the osteonectin antibody reaction and prognosis could not be established. Evidence of osteonectin was also found in other bone tumors. Osteonectin is therefore unsuitable for differential diagnosis, cannot be regarded as a bone specific protein and has not prognostic value. PMID- 1622862 TI - Chemofiltration and chemoembolization: new techniques in advanced pelvic bone malignancies. Case report on three cases. AB - The survival time and the quality of life in patients with advanced pelvic bone malignancies are still challenges for oncologists. In order to ameliorate the poor results that surgery and chemotherapy can routinely offer, we developed new loco-regional approaches like intra-arterial chemotherapy, alone or combined with chemofiltration of venous return, and chemoembolization. Chemofiltration makes it possible to cut off the high systemic drug peaks by filtering the venous drainage of a body area arterially infused. Chemoembolization causes a reduction of blood flow and therefore a prolongation of the transit time through the neoplasm vascular bed; this will increase the contact time between the drugs and the tumor cells. Three patients were treated with our loco-regional treatments and the results are reported below. PMID- 1622863 TI - Primary chemotherapy and delayed surgery for osteosarcoma of the extremities with synchronous metastases. AB - From September 1986 to September 1989 11 patients affected by osteosarcoma of the extremities with synchronous metastases were treated with two cycles of high-dose methotrexate i.v., cisplatin i.a. and adriamycin i.v. followed by simultaneous resection of the primary and metastatic tumor. A complete histological examination of the resected specimens was always performed to evaluate the percentage of necrosis produced by chemotherapy on both the primary and metastatic tumor. After surgery the patients received 3 more cycles of the same drugs as used preoperatively plus ifosfamide. The histological response of the primary tumor was 'good' (90% or more tumor necrosis) in 4 patients and 'poor' (less than 90% of tumor necrosis) in 7, while in the 34 metastatic nodules the resulting necrosis was good in 8 and poor in 26. A good correlation between the histological response in the primary and metastatic tumor was observed, particularly for poor responders (91% of poor responses also in metastatic nodules). At an average follow-up of 42 months, only 3 patients are alive, 2 disease-free, and one with uncontrolled disease. These data suggest that the prognosis of osteosarcoma of the extremities with synchronous metastases remains poor, even with a very aggressive treatment. Our results also seem to confirm the validity of the present strategy in the treatment of non-metastatic osteosarcoma: introducing new drugs post-operatively in poor responding patients can allow a better treatment of microscopic disease and can improve the prognosis for these patients. PMID- 1622864 TI - Primary childhood osteosarcoma: the role of salvage surgery. AB - The overall results of salvage surgery for lung metastases were evaluated on 174 consecutive patients with primary osteosarcoma below the age of 20, resected in Milan between 1970 and 1988. Seventy-two children treated in the years 1970-1981 were compared with 102 children treated in the years 1982-1988. In the latter period, adjuvant chemotherapy was replaced by neo-adjuvant programs and salvage surgery was applied systematically to all patients with resectable lung metastases through median sternotomy. During the last period, the overall 5 year survival improved significantly from 35% to 58% (P less than 0.001), while the disease free survival rose from 38% to 45% (median 15 vs. 33 months, P = 0.3). The proportion of patients with completely resected lung metastases rose from 17% (7/42) to 55% (27/49), without operative mortality, and the overall survival from detection of lung metastases (including unresected cases) improved from 0 to 28% at 5 years (P less than 0.001). The survival benefit was observed only in the group of children with resected metastases. These data indicate that systematic bilateral pulmonary resection, combined with neoadjuvant chemotherapy, has contributed to improve the final cure rate of childhood osteosarcoma. PMID- 1622865 TI - Osteosarcoma of the facial bones. AB - Maxillo-facial osteosarcoma is a rare primary tumor in adults. Between 1980 and 1990, 11 patients were considered; 6 had primary tumors in mandible and 5 in the maxillo-paranasal region. All cases were treated with surgery as the primary modality. Resection was radical in 8 patients and palliative in the other 3. Adjuvant postoperative chemotherapy with adriamycin was administered for 6 months in the 8 patients treated with complete resection. After a median follow-up of 3 years, 7 patients are still alive and 4 died of progressive disease. In the group of patients treated with radical surgery and adjuvant chemotherapy only one died for distant metastases, and 7 are living free of disease. With complete surgical resection long term local tumor control was achieved in all patients. No patient treated with incomplete resection achieved local tumor control with subsequent radiotherapy. The possibility of performing a complete surgical resection of the primary appears to be an essential step to obtain long term local control and survival in maxillo-facial osteosarcoma. Our series is, however, too limited to evaluate the therapeutic benefit of adjuvant chemotherapy. PMID- 1622866 TI - The value of immunohistochemistry in the diagnosis of soft tissue sarcomas. AB - Histological classification of soft tissue sarcomas can be made by light microscopy alone for those tumors with unique appearances, while a significant proportion of sarcomas require the implementation of electron microscopy or immunohistochemistry to obtain a final diagnostic classification. Immunostaining methods are particularly valuable in certain classes of sarcomas such as epithelioid sarcomas, malignant schwannomas, hemangiosarcomas, clear cell sarcomas, rhabdomyosarcomas, pleomorphic liposarcomas, leiomyosarcomas and synovial sarcomas through documentation of their cellular products. Immunohistochemistry is not a substitute for skilled interpretation of conventionally stained microscopic specimens; however, the availability of more specific determinants in the soft tissue neoplasms will expand the value of this approach in this area of diagnostic pathology. PMID- 1622867 TI - Soft tissue sarcomas. Imaging: an integrated approach. PMID- 1622868 TI - Soft tissue lesions in adults: biopsy--yes or no? PMID- 1622869 TI - Surgical approach to soft tissue sarcomas of the extremities. AB - Authors emphasize the primary role of surgery in the treatment of soft tissue sarcoma, confirming the recent acquisition that conservative surgery and adjuvant therapy yield results comparable to those of more extensive surgery. Subsequently, the authors delineate the general guidelines in the surgical treatment of soft tissue sarcoma, depending on the anatomic location of the tumor, and point out the main goals: first to provide local control of the tumor, and second to preserve as much function as possible without jeopardizing the adequacy of the procedure. PMID- 1622870 TI - Soft tissue sarcomas: experience with intraoperative brachytherapy in the conservative management. AB - Forty-eight patients with soft tissue sarcomas were treated with Iridium implant after wide local excision between 1980 and 1990 at our institution. External irradiation was also given postoperatively in 33 patients with initially resectable tumours (treatment A) and preoperatively in 3 with initially unresectable tumours (treatment C); brachytherapy was the only treatment in 12 patients presenting small superficial tumours or recurring after previous irradiation (treatment B). Median follow up was 51 months (range 6-148). Fifteen patients (31%) failed; local recurrence was present in 9 (18.8%) and distant metastases in 11 (22.9%). Local failures were 3/33 (9%) after the treatment A, 4/12 after the treatment B, 3/2 after the treatment C. The incidence of local failures was affected by the tumor size, the presence of positive histology at the resection margins, and the total radiation dose. There was no impairment of wound healing and no necrosis; a severe sclerosis was observed only in the 3 patients receiving preoperative irradiation probably because large size fractions were used. We concluded that brachytherapy should be included in the radiation program for soft tissue sarcomas when a satisfactory geometry may be achieved and in particular when the tumor is located in sites where external irradiation only has a higher probability of producing major side effects. PMID- 1622871 TI - Intra-arterial induction chemotherapy for soft tissue sarcomas. AB - One hundred-one patients were treated in our institution with intra-arterial preoperative adriamycin (i.a. ADR) for large soft tissue sarcomas of the extremities, 45% recurrent at entry. Of the 78 high grade evaluable patients 38% had clinical and 45% had pathological responses to chemotherapy. Limb conservative surgery was performed in 80% of cases, with about 10% improvement made possible by the preoperative treatment. The local recurrence rate was 29%, and 50% five-year actuarial survival with a median follow-up of 68 months. These poor results are related to the severe selection of high risk cases. The clinical parameter of response was highly predictive of survival: 63% versus 36% (p = 0.01) 5-year survival in the group of responders and non-responders, respectively, whereas the pathological parameter of response was not so predictive. The improved effect of delivering the drug intra-arterially is theoretically expected but not proved in our experience. The major practical effect of this induction chemotherapy is the selection of patients with better prognosis and the possibility of perform, in some cases, easier limb salvage procedures. The last regimen combining i.a. ADR + i.v. Ifosfamide seems to provide little better but not yet significant results. PMID- 1622872 TI - The treatment of osteosarcoma: present trends. The Scandinavian Sarcoma Group experience. AB - The study comprised 97 patients treated by the Scandinavian Sarcoma Group for high-grade, extremity-localized osteosarcoma. Chemotherapy was according to the T 10 protocol, with four courses of high-dose methotrexate (HDMTX) given preoperatively at weekly intervals. Seventeen percent of the patients obtained a good (grade III or IV) histologic response, 62% a moderate (grade II) response and 21% a poor (grade I) response. Grade II-IV responders had significantly higher serum MTX levels than grade I responders. Good responders had significantly better survival than moderate/poor responders, and had a trend towards both lower recurrence rate and longer time to recurrence. Five-year overall and relapse-free survival for all patients was 63% and 53%, respectively. Within a group of patients with similar primary tumour response, there was a trend for better survival with increasing serum MTX levels, indicating that individualization of MTX doses according to renal excretion rates may be indicated. The present results underline the importance of introducing effective chemotherapy from the start of osteosarcoma treatment, and that HDMTX alone seems to be insufficient preoperative therapy. The toxicity of HDMTX is generally mild, but we have by cerebral MRI found signal changes in white matter in 14/22 patients; changes that may represent subclinical MTX CNS toxicity. In the subsequent SSG osteosarcoma protocol, cisplatin and doxorubicin has been added to HDMTX from the start of treatment. Our data also suggest that an aggressive approach involving second-line chemotherapy and surgery is indicated for metastatic disease and that such an approach may lead to long-term survival in up to 30% of patients. PMID- 1622873 TI - Hyperthermic antiblastic perfusion for the treatment of soft tissue limb sarcoma. AB - Eighty patients with locally advanced, high grade soft tissue sarcoma of the extremities were studied prospectively in order to determine the efficacy of hyperthermic antiblastic perfusion (H.A.P.) as the first step of a combined multimodality therapy. All of the patients have been evaluated in terms of functional results, loco-regional control and survival according to the different treatment schedules adopted. The first clinical trial employed H.A.P., followed by surgery alone. Because the results obtained were unsatisfactory, the protocol was modified to include a continuous intra-arterial (i.a.) infusion of doxorubicin (dx) or radiotherapy before surgery. The best results have been obtained with the radiotherapy-including protocol showing a conservative surgery rate of 100% and a 94% rate of loco-regional control. The disease-free, distant disease-free and overall survival rates were 68%, 75% and 70%, respectively. The importance of the treatment protocol has been confirmed in a multivariate analysis which demonstrated that the treatment protocol adopted is one of the prognostic factors with an independent value (p = 0.06). PMID- 1622874 TI - Chemotherapy in the multidisciplinary approach to soft tissue sarcomas. EORTC Soft Tissue and Bone Sarcoma Group studies in perspective. PMID- 1622875 TI - Standard and high dose chemotherapy for advanced soft tissue sarcomas. AB - While significant improvements have been made in the management of localized soft tissue sarcomas, enabling the realization of better functional results and a better overall outcome, progress in metastatic disease has been less than impressive. Adriamycin and DTIC based chemotherapy programs have resulted in response rates of upto 50%, with a small but finite cure fraction, especially in conjunction with surgical resection of residual abnormalities. The decade of the 80s experienced a considerable amount of enthusiasm in exploring the role of ifosfamide and mesna, and identified its definite usefulness as an effective salvage regimen with response rates of approximately 25%-30% in adriamycin failures. Studies evaluating the role of ifosfamide as up-front line agent in combination with adriamycin have met with increased toxicities without a significant additive therapeutic benefit, probably as a result of compromised dose intensity of each individual agent. The steep linear log-dose response relationship of alkylating agents and adriamycin constitutes the theoretical rationale for use of higher doses of chemotherapy, which have become feasible, with the advent of growth factors for bone marrow support. While this approach seems promising in its infancy, with improved complete and overall response, its ultimate effect on survival is anxiously awaited. The limited experience available in the literature with even more aggressive approaches like marrow ablative doses of chemotherapy followed by bone marrow transplantation, have been uniformly disappointing, with extremely short lived responses and extremely high morbidity and cost. As clinical research continues to improve our understanding and ability to implement the currently available therapeutic armamentarium, the search for newer and better drugs needs to continue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1622876 TI - Risk factors for adult soft tissue sarcoma in northern Italy. AB - The role of several potential risk factors in the etiology of soft-tissue sarcoma (STS) was examined in a hospital-based case-control study, conducted in the Friuli-Venezia Giulia region, northeast Italy, between 1985 and 1991. A total of 93 STS cases (53 males and 40 females, median age: 52 years) and of 721 controls (371 males and 350 females, median age: 54 years) were interviewed. Significant increased risks were associated with a history of herpes zoster infection (odds ratio (OR): 2.3, 95% confidence interval (CI): 1.1-4.9), chicken-pox (OR: 2.1, 95% CI: 1.2-4.1) and mumps (OR: 2.0, 95% CI: 1.1-3.8). None of the other medical conditions investigated - socio-economic and anthropometric indicators, tobacco smoking, consumption of alcoholic beverages, coffee and tea - seemed to affect STS risk. No risk elevation was found in subjects employed in agriculture (OR - for greater than 10 years employment = 0.8, 95% CI: 0.4-1.5), nor in those who reported exposure to pesticides or herbicides (OR = 0.4, 95% CI: 0.1-1.2). Workers who reported exposure to chemical agents or to benzene or other solvents for more than 10 years had, respectively, a 1.8-fold (95% CI: 0.7-4.4) and a 2.2 fold (95% CI: 0.9-5.5) higher risk of developing STS. PMID- 1622877 TI - The prognostic value of DNA content measured by image cytometry in soft tissue sarcomas. AB - Nuclear DNA content in soft tissue sarcoma was determined by image cytometry using archival, paraffin embedded material. In a retrospective study 138 specimens of 81 patients have been analysed. The ploidy level was correlated to clinical outcome regarding tumor volume and histological grading, the most important prognostic parameters. Ploidy has a significant prognostic value and correlates well with histological grading (p = 0.01). Tumour volume was found to be an independent prognostic factor (p = greater than 0.1) [chi 2 test]. The DNA content of the primary tumour and of multiple local recurrences remained similar. PMID- 1622878 TI - Surgery and radiation therapy in the treatment of soft tissue sarcomas of extremities. AB - Between January 1979 and December 1987, 99 patients (pts.) with a diagnosis of localized soft tissue sarcoma of the extremities received preoperative radiation therapy (Preop. RT, 50 pts.) or postoperative irradiation (Postop. RT, 49 pts.). In the preop. RT group, doses ranged from 42 Gy/17 fractions to 51 Gy/17 fractions; pts. treated with RT after surgery, received a dose comprised between 46 Gy/23 fractions to 66 Gy/33 fractions. The surgical procedure consisted of making a wide resection of the mass with preservation of the affected limb, in each patient. The main cause of failure was dissemination of the disease (33.3%). The incidence of local failures was low (7.1%). Recurrences were related to the size of the disease (5 cm: 0/12; 5-10 cm: 2/45 2.3%; 10 cm: 5/42, 11.9%), as were also distant metastases. The incidence of distant failures was higher in the group treated with preop. RT (44.0% vs. 22.4%), probably because a higher percentage of patients in this group had large volume diseases. Late sequelae were evaluable in 59 pts. with a follow up longer than 24 months. The incidence of complications was low (10.1%, 6/59); it was higher in the preoperative than in the postoperative group (15.4% vs. 6.1%); this observation is probably related to the different modalities of fractionation. PMID- 1622879 TI - Radiation therapy and conservative surgery for soft tissue sarcomas of the extremities, torso and head and neck. AB - Between May 1985 and July 1990, 45 patients (pts.) with primary (39) or recurrent (6) soft tissue sarcomas of the extremities (82%), torso (11%) and head and neck (7%) were treated with radiation therapy and conservative surgery. Seven pts. not amenable to conservative surgery underwent preoperative radiation therapy whereas 38 pts. underwent local excision and post-operative radiation therapy. Out of the 38 pts. managed by postoperative radiation, 24 (63%) showed negative surgical margins and 14 (37%) positive margins, their tumor being adjacent to vital structures. Preoperative radiation allowed conservative surgery in all 7 pts. with initially inoperable tumor; surgical margins were negative in 5 and positive in 2 pts. Twenty-six pts. (58%) had tumor greater than or equal to 5 cm (5-24) and 19 (42%) less than 5 cm (2.5-4.5) in diameter. High grade tumors (G2-G3) were reported in 41 pts. (90%). In pts. treated postoperatively the radiation dose was 64-66 Gy/32-33 fractions and the pts. treated preoperatively received a dose of 50 Gy/25 fractions. Median follow-up was 33 months and all pts. had a minimum follow-up of 12 months (12-72). Three pts. (6.5%) had local failure and 9 (20%) developed distant metastases with local tumor control. All distant metastases occurred in AJC stage IIIB, 9/18 (50%), with an increased frequency by tumor size. Overall local control and disease free survival rates at 5 years (product limit method) were 93% and 73%, respectively. An evident decrease in disease-free survival rate (33%) was noted for stage IIIB pts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1622880 TI - Training in clinical oncology: results of a Junior Radiologists' Forum Questionnaire. PMID- 1622881 TI - Sites of relapse in seminoma treated with single agent carboplatin chemotherapy: implications for further management. AB - Between 1983 and 1990, 66 patients were treated with single agent carboplatin for advanced seminoma, and sites of relapse have been analysed with respect to sites involved before chemotherapy. Fourteen relapses were evaluable, and relapse was confined to node groups affected before chemotherapy, or those immediately adjacent, in seven patients. At present it is unclear whether single agent carboplatin should be the initial chemotherapy for seminoma, but if it is employed there may be a role for local adjuvant radiotherapy after carboplatin chemotherapy. PMID- 1622882 TI - The problem of cigarette smoking in radiotherapy for cancer in the head and neck. AB - Smoking cigarettes during radiotherapy prolongs the period of reaction and may reduce the chance of cure. Of a group of 48 patients with advanced head and neck cancer 35 were smoking at the time of diagnosis, but 17 were persuaded to stop, although 7 relapsed later. Interviews conducted in 35 of the 48 patients revealed the problems which must be overcome if such patients are to cease smoking. PMID- 1622883 TI - Primary radiotherapy for T4 breast cancer. AB - In Edinburgh in 1982, radiotherapy for patients with T4 breast cancer was modified by an increase in tumour absorbed dose from 42.5-45.0 Gy to 60-75 Gy by using tumour boosts and changing from alternate day to daily fractions. To assess whether this improved local control or survival, the records of all females with T4-N0-3M0 breast cancer referred between January 1978 and December 1985, who received radiotherapy without initial mastectomy or adjuvant chemotherapy, were reviewed. There were 193 patients in the study. Minimum follow-up was 36 months. Actuarial survival at 5 years was 27.1% and median survival 29 months. Local control was achieved by 25.9%. On multivariate analysis, the probability of survival fell with increasing tumour size, advanced clinical node status and the presence of inflammatory change. Radiotherapy technique also affected prognosis. Four-field techniques were associated with a better chance of survival than the breast and axillary jig or other treatment methods. The probability of local control increased with reduced tumour size and showed the same relationship to radiotherapy technique as did survival. Dose was not a significant variable for either survival or local control. No improvement in survival or local control was apparent in comparison with a previous study. It is concluded that radiotherapy alone at a dose of 60 Gy is insufficient to produce durable local control for the majority of women with T4 breast cancer. PMID- 1622884 TI - The use of isodose curves on radiographs and on CT scans in interstitial brachytherapy. AB - In brachytherapy an accurate dose distribution is usually not definable, and therefore not required. If flexible catheters are implanted, such as in head and neck cancer, resulting isodose curves only rarely fit exactly to radiographic films, and the target volume is not easily reconstructed. Usually no clear relationship exists between the three-dimensional (3D) dose distribution and target volume on the one hand and the two-dimensional (2D) radiographic films on the other. Dose distributions on radiographs are not sufficient to define the target absorbed dose and doses that critical areas will receive. A 3D imaging system, like computed tomographic (CT) scans, is needed in order to visualize underdosage inside the target volume and non-tolerable hot spots outside the tumour. Large-scale and expensive techniques exist to tackle these problems. Our inexpensive and verifiable approach to solve these problems combines localization radiographs with CT scans. Whereas tumour and critical areas are displayed on CT scans, flexible catheters loaded with dummy sources are best seen on radiographic films. With the help of a self-developed computer program, dose distributions are superimposed on CT scans. Doses to the target and critical organs are easily read and verified by external and internal detectors. PMID- 1622885 TI - The role of a radiographer counsellor in a large centre for cancer treatment: a discussion paper based on an audit of the work of a radiographer counsellor. AB - It is widely accepted that cancer patients have unmet psychosocial needs. There are as yet few guidelines on the appropriate role of a counsellor in centres for cancer treatment. In this study the activities of a radiographer counsellor were audited to try to identify the proportion of patients who would benefit from seeing a counsellor, to estimate the cost of such a service, and to obtain indications of how the effects of counselling could be evaluated. The study suggested that 44% of patients attending for routine radiotherapy have abnormally high levels of anxiety and might benefit from counselling. The Hospital Anxiety and Depression Scale (HADS) is proposed as an objective measure of benefit. Costing and resource allocation are discussed. PMID- 1622886 TI - Irradiation of the pinna with superficial kilovoltage radiotherapy. AB - Excellent local control can be achieved by treating superficial carcinomas of the skin with superficial kilovoltage radiotherapy. The results of this study support the use of 100-140 KV photons to treat carcinomas of the skin of or around the pinna. This achieves a local control rate of 97% and the radionecrosis rate of 10% could be halved if all patients were treated with 3500 cGy in 5 fractions over one week, or to a maximum area of 5 cm2 of irradiated pinna. An audit of the running cost reveals that this method of treating superficial carcinomas is highly cost effective and can be recommended for all suitable patients. PMID- 1622888 TI - The 1991 George Edelstyn Memorial Lecture: needles, wires and chips--advances in brachytherapy. AB - The majority of quantitative data on the effects of dose-rate come from experiments with cultured cells in vitro. These data are reviewed, and it is concluded that results obtained from the in vitro experience may be carried over, in a quantitative manner, to guide clinical radiotherapeutic design. As an example, there are contradictory guidelines suggested to compensate for changes in dose-rate in interstitial wire-implant brachytherapy. The Paris group has suggested no dose correction is required for implant times from 3 to 8 days, while the Paterson/Ellis school suggests a significant correction. It is shown that, based on known radiobiological principles, this controversy can be resolved. These same radiobiological notions, as well as advances in computer technology, have led to the technique of pulsed brachytherapy, which allows the average dose-rate to be maintained at a constant rate, even when the wire activities have decayed. PMID- 1622887 TI - The management of tumours arising in the maxillary antrum. AB - Eighty-eight cases of tumours arising in the maxillary antrum undergoing treatment between 1967 and 1989 are reported. The series comprised 34 females and 54 males. Sixty-two patients had squamous cell carcinoma (SCC). Forty of those with SCC were treated by XRT only, four cases by surgery only, while the remaining 18 patients had surgery and post-operative XRT as a combined modality treatment. Early SCC (T2N0) was adequately controlled by radical radiotherapy alone with a 5-year survival of 69.1%. In more advanced SCC (T3N0 and (T4N0) radical radiotherapy alone was less successful with the 5-year survival falling to 19%. Combined modality treatment comprising radical surgery followed by radical postoperative radiotherapy improved 5-year survival in advanced SCC to 61%. It is therefore recommended that if patients are treated for cure, major surgery followed by radical postoperative radiotherapy is preferable in advanced squamous tumours ((T3/T4) of the maxillary antrum. PMID- 1622889 TI - Are we winning the war against cancer? A review in memory of Keith Durrant. PMID- 1622890 TI - Hypertrichosis lanuginosa acquisita following cytotoxic chemotherapy. AB - Hypertrichosis lanuginosa acquisita (HLA) refers to abnormal and excessive growth of fine downy hair. It is a rare condition which has been reported in association with both malignancy and certain drug therapy. We report three cases occurring after administration of cytotoxic chemotherapy for cancer. A possible relationship is discussed and previous literature reviewed. PMID- 1622891 TI - Demonstration of the requirement for self antigen in the activation of autoreactive T cells. AB - An HLA-DR4-restricted T cell clone (26G11), which was reactive to autologous non T cells without any nominal antigens, was established from an unimmunized normal subject that was DR1/4 positive. The reactivity of the clone was examined against L cells (LDR4) transfected with the particular DR4 genes obtained from the same subject. 26G11 cells proliferated slightly in response to LDR4 cells, but the proliferation was markedly augmented by the addition of cell lysate from an autologous B cell line. In addition, 26G11 cells killed LRD4 cells sensitized by preincubation with the cell lysate more efficiently than LDR4 cells without treatment. When LDR4 cells were preincubated with cell lysate from allogenic B cell lines, effective killing of the target cells by clone 26G11 was also observed. These data strongly suggest that this autoreactive T cell clone (26G11) recognizes endogenous antigen in the context of the DR4 molecule. This directly demonstrates the requirement for self antigen in the activation of human autoreactive T cells from a normal subject. PMID- 1622892 TI - Characterization of private and cross-reactive idiotypes associated with human antibodies to hepatitis B surface antigen. AB - Four mouse monoclonal anti-idiotypic antibodies (anti-Id) were generated against human monoclonal and polyclonal antibodies to hepatitis B surface antigen (HBsAg). These monoclonal anti-Id, along with a polyclonal anti-Id raised in rabbits, were used to characterize the idiotype (Id) specificity of the human antibody response to HBsAg (anti-HBs). The anti-Id reagents identified distinct private and cross-reactive Id expressed on monoclonal and polyclonal human anti HBs preparations respectively. The anti-Id recognized both HBsAg combining site and non-combining site related private Id, and HBsAg combining site related cross reactive Id. The Id specificities recognized by two of the monoclonal anti-Id were associated with the H chain alone, whereas two of the monoclonal anti-Id, along with the polyclonal anti-Id appeared to recognize Id determinants associated with both isolated H and L chains. These data suggest that Id heterogeneity exists within the human antibody response to HBsAg. The knowledge that Id heterogeneity exists is of importance in understanding the observed variability in the immune response during hepatitis B virus infection. PMID- 1622893 TI - Antigen recognition by the T cell receptor is enhanced by CD8 alpha-chain binding to the alpha 3 domain of MHC class I molecules, not by signaling via the cytoplasmic domain of CD8 alpha. AB - The binding specificities and function of mouse CD8 were studied using a CD4-CD8- allospecific T cell hybridoma, chimeric class I MHC molecules, and a CD8 alpha deletion mutant. By transfecting the mouse CD8 alpha gene into a IL-2 producing, H-2Kb specific hybridoma, IL-2 production was increased when L cells expressing Kb were used as stimulators. However, no increase in IL-2 was observed when a KbKbB7 hybrid molecule, composed of the alpha 1 and alpha 2 domains of H-2Kb, and the alpha 3 domain of HLA-B7, was used as a stimulator. Comparison between T cell hybridomas that expressed full-length CD8 alpha and a deletion mutant lacking part of the cytoplasmic domain revealed identical responsiveness for H-2Kb. The data suggest that the mouse CD8 alpha homodimer does not bind to the alpha 3 domain of HLA class I molecules and that CD8 alpha acts as a co-receptor with the TCR by binding the same MHC molecule for alloantigen recognition. Our data also provide evidence that CD8 alpha signal transduction through its cytoplasmic tail by association with p56lck is not an absolute requirement for antigen recognition by T cells. PMID- 1622894 TI - Development and follicular localization of tolerant B lymphocytes in lysozyme/anti-lysozyme IgM/IgD transgenic mice. AB - To analyse mechanisms of immunological self-tolerance, a detailed comparison of the development and fate of lysozyme-specific B lymphocytes was carried out in transgenic mice expressing rearranged anti-lysozyme IgM/IgD Ig transgenes in the absence or presence of an additional transgene encoding lysozyme itself. In the absence of lysozyme, B cell development, localization, and differential expression of transgene-encoded IgM and IgD occurred in the normal sequence in Ig transgenic mice, establishing that these animals provide a physiological model for studies of B cell selection in vivo. By contrast, in lysozyme-expressing double-transgenic mice, tolerant lysozyme-reactive B cells persisted within the follicular mantle zones in the spleen, lymph nodes, and Peyer's patches, but were eliminated from the splenic marginal zones. It could be shown that lysozyme binding and induction of tolerance occurred as soon as surface Ig was expressed on immature B cells in the bone marrow of the double-transgenic mice although this did not prevent maturation, emigration from the bone marrow, and localization in peripheral lymphoid follicles. These findings, together with recent examples of aborted maturation of self-reactive B cells, indicate two functionally distinct antigen receptor signalling events in immature B cells and suggest a unique role for the follicular microenvironment. PMID- 1622895 TI - Characterization of lymphoid cell lines from murine spleen which can localize in thymus. AB - Several murine lymphoid cell lines have been tested for specific capacity to localize in thymus. These are all continuous, cloned Radiation leukemia virus induced cell lines which have a common phenotype resembling lymphoid stem cells or immature T cells. Since each of these cell lines has a cloning efficiency approaching 100%, the number of cells which enters thymus during a 3 h homing assay has been estimated by limit dilution cloning analysis taking into account extra-binomial variation caused by individual mice. Only two out of seven of these cell lines have been found to have this specific property. These two cell lines, 16C1 and 5C2B, have been characterized as immature lymphoid cells, bearing no rearrangement at the TCR gamma and beta loci, and having the phenotype of CD3+CD4-CD8-, immature T cells. A maximum number of 2000 16C1 cells and 2500 5C2B cells can enter thymus during a 3 h homing assay, suggesting a limited number of sites in thymus to which these cells can bind. The capacity of 16C1 to enter thymus in low frequency has been found to be a stable property and was not increased by repetitive passage through mouse thymus. Using this assay, we have also been able to confirm that entry of 16C1 cells into thymus can be inhibited by antibody specific for the Ly24 (Pgp-1) molecule. PMID- 1622896 TI - Effect of in vivo hyperthermia on thymocyte maturation and selection. AB - Two-month-old male mice were exposed to whole-body hyperthermic treatment in a circulating water bath. After 1 h exposure to 41 degrees C, mice were kept at room temperature for 24, 48, 72, and 96 h before thymus examination. The total thymocyte number progressively decreased after 24 and 48 h, reached a minimum value at 72 h, and returned to almost normal value after 96 h. Similar changes occurred in the CD4+CD8+ cell subset. Conversely, the percentage of CD4-CD8- cells rose to a maximum at 48 h and then declined to normal value at 96 h. The percentage of CD4-CD8+ and CD4+CD8- cell subsets increased to a maximum at 48 h and then declined to normal value at 96 h. These variations in single positive cell subsets correlated well with similar changes in the thymocyte mitotic response to concanavalin A. The observed effects on thymocytes were heat dose dependent, and suggest that hyperthermia induces the development of the most primitive thymocytes and positively selects mature T cells with high mitotic responsiveness. It is proposed that heat shock proteins might be involved in the hyperthermia-induced alterations of thymocyte maturation and selection. PMID- 1622897 TI - The effect of p56lck, a lymphocyte specific protein tyrosine kinase, on the syncytium formation induced by human immunodeficiency virus envelope glycoprotein. AB - A human CD4+ T cell line, Jurkat, was transfected with a constructed plasmid, which has the envelope gene of the human immunodeficiency virus (HIV) under the transcriptional control of the human metallothionein IIA promoter, and these transfected cells were then cloned. JME2, one of the cloned cell lines, expressing the envelope glycoprotein after induction with metal ions, showed the ability to form syncytia involving other CD4+ cells not expressing the HIV envelope protein. When several CD4+ cell lines were examined for their susceptibility to syncytium formation by JME2 cells, the p56lck-expressing cell lines were found to be more susceptible to syncytium formation than the p56lck non-expressing cell lines. To substantiate the role of p56lck in the syncytium formation, a CD4+, p56lck-non-expressing monocytoid cell line, U937 clone 2, was transfected with an lck-expressing construct. Using such transfectant cell clones, it was demonstrated that p56lck-positive cells are markedly more susceptible to the syncytium formation than p56lck-negative cells, implying a regulatory role for p56lck in syncytium formation mediated by the HIV envelope and CD4 molecule. Moreover, it was suggested, in the experiments using CD45 cross linking or a protein tyrosine kinase inhibitor, genistein, that p56lck affects syncytium formation through its protein tyrosine kinase activity. A putative mechanism by which p56lck affects the syncytium formation is also discussed. PMID- 1622898 TI - Characterization and partial purification of a high molecular weight tumoricidal activity secreted by murine bone marrow macrophages. AB - Cultured murine bone marrow-derived macrophage (BMM phi) can be induced to secrete tumoricidal activity in vitro when activated with recombinant IFN-gamma and bacterial lipopolysaccharide (LPS). We have analyzed this activity for tumor specificity, relationship to tumor necrosis factor-alpha (TNF-alpha), serine proteases, and reactive nitrogen intermediates, and partially purified this activity by high pressure liquid chromatography. Cytolytic activity was recovered in conditioned culture supernatants of serum-free cultivated BMM phi treated with a combination of IFN-gamma and LPS but was not inducible by either stimulant alone. It selectively affected tumor cells of murine as well as human origin irrespective of sensitivity towards recombinant murine TNF-alpha (r-muTNF-alpha), but did not significantly affect non-tumorigenic cells of either species. It was inactivated by 56 degrees C, trypsin, and neuraminidase treatment, but could not be inhibited by neutralizing antibodies against r-muTNF-alpha or serine protease inhibitors. Tumoricidal activity was purified approximately 10-fold by gel filtration and eluted as a major peak with a Mr of 170 kDa, containing a single predominant protein band of approximately 170 kDa on SDS-PAGE analysis, which is shown to be a disulfide linked glycoprotein heterodimer of 110 and 58 kDa subunits (gp170). Expression of this glycoprotein was strongly dependent on activation of BMM phi by a combination of IFN-gamma and LPS but was only marginally induced by either stimulant alone. Furthermore, the level of gp170 expression was quantitatively correlated with the tumoricidal activity of BMM phi culture supernatants, whereas no such correlation was found with respect to the amount of secreted TNF-alpha or reactive nitrogen intermediates. These data demonstrate that activated murine BMM phi secrete a tumoricidal activity, which is not related to TNF-alpha, serine proteases, or reactive nitrogen intermediates, but is closely associated with a 170 kDa glycoprotein composed of two subunits with Mr's of 110 and 58 kDa. PMID- 1622899 TI - Binding of low concentration of peptide to H-2Kd produced in insect cells requires mouse beta 2-microglobulin co-expression. AB - A recombinant baculovirus expressing the murine class I MHC heavy chain H-2Kd cDNA under the transcriptional control of Autografa californica nuclear polyhedrosis virus (AcNPV) polyhedrin promoter has been isolated and used to infect Sf9 lepidopteran cells either alone or in association with a previously isolated virus expressing mouse beta 2-microglobulina (beta 2-ma). When infected with the heavy chain-encoding virus alone, H-2Kd was produced in a beta 2-m-free conformation detected on the surface of infected cells by conformation independent antibodies. When Sf9 cells were co-infected with both viruses, approximately 10% of the heavy chain pool was engaged in the formation of native heterodimeric MHC class I molecules, which were glycosylated and transported to the cell surface as demonstrated by radio-binding experiments and flow cytometry. The assembly of the recombinant class I molecule was dependent on peptide, since heterodimer formation was brought about by H-2Kd-specific peptide ligands both in vivo, upon incubation with dually infected cells, and in vitro, in cell-free detergent extracts. In addition, a change in heavy chain conformation was brought about upon incubation with high concentrations (100 microM) of an H-2Kd restricted octapeptide epitope from Plasmodium berghei. Furthermore, using low concentrations (3 nM) of a photoaffinity label derivative of this peptide, we show direct binding to cells co-expressing class I heavy chain and mouse beta 2-m but not to cells expressing free heavy chain only. PMID- 1622900 TI - Isolation of human minor histocompatibility peptides. AB - Incompatibility of human minor histocompatibility (hmH) antigens induces rejection of grafts in organ transplantation and graft versus host disease in bone marrow transplantation if donor and recipient are matched for human leukocyte antigen (HLA) genes. These antigens are recognized only by T cells. We describe here the isolation of hmH peptides recognized by a hmH antigen specific, HLA-B35 restricted CTL clone which was derived from a patient who rejected the kidneys from two HLA-identical sisters. Naturally occurring hmH peptides were isolated from a donor derived B cell line and an HLA-B35 transfected human B cell line by acid elution. Analysis of various HLA class I transfectant cells demonstrated that MHC class I molecules themselves determine the peptides which are naturally processed and presented to T cells. PMID- 1622901 TI - Eclampsia in the United Kingdom. The 'BEST' way forward. PMID- 1622902 TI - Terminology used in early pregnancy loss. PMID- 1622903 TI - Action in international medicine and maternal health care in developing countries. PMID- 1622904 TI - A randomized prospective study comparing delivery with metal and silicone rubber vacuum extractor cups. AB - OBJECTIVE: To determine the relative benefits and complications of assisted vaginal delivery with metal and silicone rubber vacuum extractor cups. DESIGN: Prospective randomized controlled study. SETTING: A busy referral maternity hospital in Kathmandu, Nepal. SUBJECTS: 101 women were assigned to delivery with the Silc-cup and 98 to delivery with the metal cup. MAIN OUTCOME MEASURES: Success rate at achieving delivery with the assigned instrument and incidence of neonatal trauma. Analysis was by 'intention to deliver' with women remaining in their original group regardless of the eventual mode of delivery. RESULTS: Randomization resulted in two groups of women similar in respect of age, parity, gestation and indication for delivery. The overall success rate was similar for the two instruments (Silc-cup 85% and metal cup 87%). The Silc-cup was more likely to fail if there was excessive caput (seven failures compared with one in the metal cup group). The frequency of clinically significant maternal trauma was low in both groups. There were fewer babies with clinically significant scalp trauma in the Silc-cup group (22%), compared with the metal cup group (37%). CONCLUSIONS: The data indicate a greater tendency for the Silc-cup to fail when excessive caput is present but that metal cups are associated with increased scalp injuries. PMID- 1622905 TI - Intra-operative blood loss during elective lower segment caesarean section. AB - OBJECTIVE: To measure intra-operative blood loss at elective lower segment caesarean section and to compare estimated with measured blood loss. DESIGN: Prospective observational study. Blood loss was measured in patients who underwent lower segment caesarean section in the course of routine hospital activity. SETTING: Tsan Yuk Hospital (Hong Kong), which is affiliated to the University of Hong Kong, 1990-1991. SUBJECTS: Forty women (mean age 29 years) with singleton pregnancies (mean gestation 38 weeks) delivered by elective lower segment caesarean section under general anaesthesia (mean birthweight 3177 g). MAIN OUTCOME MEASURE: Intra-operative blood loss measured by the alkaline haematin method (intra-assay co-efficient of variation 2.2%). RESULTS: The mean measured blood loss was 487 ml (SE 40, range 164-1438). The mean estimated blood loss was 425 ml (SE 31) range 100-1300; mode 400). Observer error in estimating blood loss was higher if measured blood loss greater than 600 ml. One patient received a blood transfusion and another had a post-operative haemoglobin level less than 10.0 g/dl. CONCLUSION: Blood loss at elective lower segment caesarean section was usually less than 500 ml and was estimated with reasonable accuracy. However, there was a tendency to under-estimate blood loss when the measured loss exceeded 600 ml. PMID- 1622906 TI - Thyroxine dosage during pregnancy in women with primary hypothyroidism. AB - OBJECTIVE: To assess whether pregnancy changes the thyroxine requirements of hypothyroid women. DESIGN: A retrospective, longitudinal study. SETTING: Queen Charlotte's and Chelsea Hospital for Women. SUBJECTS: 32 women referred for antenatal care during 35 pregnancies. MAIN OUTCOME MEASURES: Changes in thyroid stimulating hormone (TSH) and free thyroxine (fT4) levels as pregnancy progresses. RESULTS: In most of the pregnancies (80%), no change in thyroxine dose was required (mean dose 129 micrograms). The mean TSH levels in early (1.8 mU/l) and in late pregnancy (1.5 mU/l) were unchanged (P greater than 0.5). In the remaining pregnancies, thyroxine dose was increased after the first antenatal clinic appointment, on the basis of thyroid function test results, from a mean of 104 micrograms to a mean of 172 micrograms (P less than 0.01). These women had a mean early pregnancy TSH of 12.3 mU/l, which decreased by 95% to 1.3 mU/l (P less than 0.01). CONCLUSIONS: Most of the hypothyroid patients presenting to an antental booking clinic are well controlled in early pregnancy and will remain so throughout pregnancy. The dose of thyroxine does not need to be changed, and further assessments of thyroid function should not be necessary. It is unlikely that the patients were all 'overtreated' before conception, since they were referred to us by a large number of independent doctors. Women who are under treated before the pregnancy are likely to require both increased thyroxine dose and further thyroid function assays. They can generally be easily detected, biochemically, at the first hospital visit. PMID- 1622907 TI - A randomized placebo-controlled study of the effect of low dose aspirin on platelet reactivity and serum thromboxane B2 production in non-pregnant women, in normal pregnancy, and in gestational hypertension. AB - OBJECTIVE: To investigate the effect of 60 mg aspirin daily on platelet reactivity and prostaglandin production in various groups of patients. Similar regimens, which are thought to act through inhibition of platelet thromboxane production, are currently undergoing clinical assessment for the prevention of pre-eclampsia and intrauterine growth retardation. DESIGN: A prospective randomized placebo controlled study. SETTING: University Hospital, Nottingham. SUBJECTS: 12 non-pregnant female volunteers, 18 normal primigravidae before 16 weeks gestation and 16 pregnant women admitted with gestational hypertension (GH) at a mean gestation of 38 weeks. INTERVENTIONS: In the non-pregnant women blood samples were taken before and after a 10-day course of 60 mg aspirin daily. The primigravidae had blood samples taken at 16 weeks and then they were randomized to receive either 60 mg aspirin daily or a matched placebo. Further blood samples were obtained at 28, 32 and 36 weeks. MAIN OUTCOME MEASURES: Changes in platelet reactivity and release reaction, and serum thromboxane production, were estimated in whole blood. RESULTS: 60 mg aspirin daily significantly inhibited cyclo oxygenase dependent platelet aggregation, release reaction and serum thromboxane production in non-pregnant and pregnant women, and in women with GH (P less than 0.01). When adrenaline was used as the aggregating agent, the cyclo-oxygenase pathway was recruited in the increased reactivity seen in the third trimester of normal pregnancy, and was sensitive to inhibition by low dose aspirin. CONCLUSION: Low dose aspirin would appear to be an appropriate agent for the inhibition of platelet reactivity associated with hypertensive pregnancy. PMID- 1622908 TI - The characteristics of the second stage of labour in 25,069 singleton deliveries in the North West Thames Health Region, 1988. AB - OBJECTIVE: To define the contemporary characteristics of the second stage of labour in one Health Region. DESIGN: Retrospective analysis of a regional obstetric database. SETTING: Seventeen maternity units in the North West Thames Health Region. SUBJECTS: Selected from 36,727 consecutive singleton deliveries in 1988. The analysis was confined to the 25,069 women delivered of an infant of at least 37 weeks gestation with a cephalic presentation following the spontaneous onset of labour. MAIN OUTCOME MEASURES: Second stage duration, obstetric intervention and maternal and fetal morbidity. RESULTS: The duration of the second stage and the use of operative intervention were strongly negatively associated with parity and positively associated with the use of epidural analgesia. Maternal age, fetal birthweight and maternal height were also independently associated with the duration of the second stage. There were small but significant differences in the characteristics of women using epidural analgesia and those using alternative methods of pain relief. Parous women using epidural analgesia behaved in a similar manner to nulliparae without epidurals. Despite the longer second stages observed in women using epidural analgesia there appeared to be no significant increase in fetal morbidity. Within the region the epidural rate in individual units positively correlated with the overall forceps rate, the rate of caesarean section in the second stage of labour and the duration of the second stage. CONCLUSIONS: In our study the duration of the second stage in women not using epidural analgesia was similar to previous findings, but in those using epidural analgesia, the duration of the second stage was longer than has been reported previously, possibly reflecting a more conservative approach to operative intervention. Survival analysis indicates that in multiparae not using epidural analgesia the likelihood of spontaneous vaginal delivery after 1 h in the second stage was low, but in those multiparae using epidural analgesia and in all nulliparae there was no clear cut-off point for expectation of spontaneous delivery in the near future; they continue to give birth at a steady rate over several hours. While maternal and fetal conditions are satisfactory, intervention should be based on the rate of progress rather than the elapsed time since full cervical dilatation. PMID- 1622909 TI - Neonatal and maternal morbidity in relation to the length of the second stage of labour. AB - OBJECTIVE: To investigate the relation between the duration of the second stage of labour and subsequent early neonatal and maternal morbidity. DESIGN: Retrospective analysis of a regional obstetric database. SETTING: 17 maternity units in the North West Thames Health Region. SUBJECTS: Selected from 36,727 consecutive singleton deliveries in 1988. The analysis was confined to the 25,069 women delivered of an infant of at least 37 weeks gestation with a cephalic presentation following the spontaneous onset of labour. MAIN OUTCOME MEASURES: The relative risk of early maternal morbidity, postpartum haemorrhage (PPH) and postpartum infection, and neonatal morbidity, as judged by low Apgar scores or admission to the special care baby unit (SCBU), in relation to anthropomorphic characteristics (parity and birthweight), interventions (epidural analgesia, episiotomy and operative delivery), signs of fetal compromise (meconium staining of the amniotic fluid or abnormal cardiotocography (CTG)), maternal morbidity in labour (pyrexia) and the duration of the second stage of labour. RESULTS: The duration of the second stage of labour had a significant independent association with the risk of both PPH and maternal infection after adjustment for other factors. However, there was a similar or greater risk of PPH in association with operative delivery or a birthweight greater than 4000 g. Both maternal pyrexia in labour and primiparity were associated with a greater risk of post partum maternal infection than was the duration of the second stage, although all these factors were statistically significant. In contrast, the duration of the second stage was not significantly associated with the risk of a low Apgar score or admission to SCBU after adjustment for other factors. CONCLUSIONS: The duration of the second stage of labour has a positive independent association with early maternal morbidity. We could show no such relation between time spent in the second stage of labour and the frequency of low Apgar scores or the rate of admission to SCBU. With current management approaches, in the absence of factors suggesting fetal compromise, second stage labours of up to 3 h duration do not seem to carry undue risk to the fetus. PMID- 1622910 TI - Falling incidence of hypoxic-ischaemic encephalopathy in term infants. AB - OBJECTIVE: To examine trends in the incidence of hypoxic-ischaemic encephalopathy over a 13-year period. DESIGN: A retrospective analysis of medical records of all infants admitted in the years 1976-1980 and 1984-1988. SETTING: A large non teaching district health authority in central England. SUBJECTS: Infants admitted to a district general hospital neonatal unit with clinical features of hypoxic ischaemic encephalopathy. MAIN OUTCOME MEASURES: Incidence of three grades of hypoxic-ischaemic encephalopathy, handicap and mortality. RESULTS: During the first 5-year period the overall incidence of hypoxic-ischaemic encephalopathy was 7.7 per 1000 live births with 2.6 per 1000 live births being severely affected (grades II and III). In the second 5-year period the overall incidence was 4.6 per 1000 live births with 1.8 per 1000 live births being severely affected. The difference in the overall rate is statistically significant. Of the infants with severe encephalopathy 61% had Apgar scores below 4 at 1 min and 60% were born by instrumental or operative delivery. CONCLUSIONS: The fall in incidence of hypoxic ischaemic encephalopathy has occurred during a period of falling perinatal mortality rate. It was instructive to find that infants born vaginally and without obstetric intervention formed a larger fraction of the severely affected infants in the later period. PMID- 1622911 TI - Abdominal irradiation in childhood; the potential for pregnancy. AB - OBJECTIVE: To investigate the impact of premature ovarian failure due to whole abdominal radiotherapy (DXT) in childhood on uterine physical characteristics and blood flow and measuring the uterine response to exogenous sex steroid replacement. DESIGN: A comparative observational study SUBJECTS: 10 women with premature ovarian failure due to treatment with whole abdominal irradiation in childhood. A comparison group of 22 women with premature ovarian failure who had not received whole abdominal DXT. MAIN OUTCOME MEASURES: Uterine length and uterine blood flow measurement plus serial assessment of endometrial thickness during a cycle of exogenous sex steroid replacement. RESULTS: Uterine length was significantly less (P less than 0.01) in women who had been exposed to whole abdominal DXT in childhood (mean 4.1 cm, 2SE 0.8) compared with a mean of 7.3 cm (2SE 0.6) in the comparison group. The three women in the DXT group who were studied serially had no increase in endometrial thickness in response to physiological sex steroid replacement therapy and most of the 10 irradiated women had no detectable uterine blood flow with Doppler ultrasound. CONCLUSIONS: Uterine musculature and blood flow are irreversibly affected by high dose irradiation in childhood. Non-invasive assessment of this nature may predict potential for pregnancy following ovum donation and embryo transfer. PMID- 1622912 TI - Epidermal growth factor receptor expression in normal endometrium and endometriosis: an immunohistochemical study. AB - OBJECTIVE: To study epidermal growth factor (EGF) receptor expression in endometrium throughout the menstrual cycle and to compare EGF-receptor expression in endometrium from patients with endometriosis with receptor expression in synchronously sampled endometriosis and in endometrium from healthy women. DESIGN: An immunohistochemical study of receptor expression using murine monoclonal antibodies and timed endometrial and endometriotic biopsies. SUBJECTS: 25 healthy women and 27 patients with a diagnosis of endometriosis. RESULTS: Positive staining for EGF receptors was observed in 24 of 25 samples from normal women and in 26 of 27 endometrial samples from patients with endometriosis. In neither group was there any variation in the intensity of staining throughout the menstrual cycle and both glands and stroma were stained. EGF-receptor expression was observed in the glands of 15 out of 17 endometriotic lesions and in 12 of these biopsies positive staining was also present within endometriotic stroma. CONCLUSION: This study shows no difference in the intensity of staining of EGF receptors in endometrium throughout the menstrual cycle or between the glands of normal endometrium and those of endometriosis. PMID- 1622913 TI - The epidemiology of hysterectomy: findings in a large cohort study. AB - OBJECTIVE: To examine patterns of hysterectomy in the Oxford-Family Planning Association (Oxford-FPA) study in relation to age, parity, social class and calendar period (-1974, 1975-79. 1980-84, 1985-89). DESIGN: The Oxford-FPA study is a large scale prospective study of 17,032 women recruited from 1968-74 and still under observation. SETTING: Seventeen family planning centres throughout England and Scotland. SUBJECTS: At recruitment the 17,032 women were all white, British, married, aged 25-39 and willing to co-operate. In addition, they were using the pill or an intrauterine device or a diaphragm as their method of contraception. MAIN OUTCOME MEASURE: Hysterectomy rates per 1000 woman-years of observation in various subclasses of the data. RESULTS: Up to the end of 1989, 1885 (11.1%) of the 17,032 women in the study were known to have undergone hysterectomy. Fibroids were the most common cause followed closely by menstrual disturbances in the absence of fibroids (hereafter referred to as 'menstrual disturbances'). Social class had a modest influence on hysterectomy rates. Hysterectomy for fibroids, prolapse, endometriosis and 'other reasons' showed little trend with calendar period while hysterectomy for menstrual disturbances and for cancer showed a sharp increase with calendar time especially at ages 30 39. Hysterectomy generally tended to increase with age and showed a strong relation to parity; in particular, hysterectomy for fibroids fell with parity and hysterectomy for menstrual disturbances rose sharply with parity. Using lifetable methods, it was estimated that almost 20% of the women in the study would have had a hysterectomy by age 55. CONCLUSIONS: The results give insights into factors affecting hysterectomy rates. Of particular interest is the modest influence of social class, the strong influence of parity and the rise in rates with calendar time at ages 30-39 for those undergoing hysterectomy for menstrual disturbances or cancer, but since the cohort is not directly representative of the population, some caution is required in extrapolating these findings. The estimated hysterectomy rate of about 20% by age 55 is in line with other similar estimates for the United Kingdom. PMID- 1622914 TI - Study of the birthweight of parents experiencing unexplained recurrent miscarriages. AB - OBJECTIVE: To examine birthweight and preterm birth rates in couples with unexplained recurrent miscarriages. DESIGN: A case control study. Birth data of couples with recurrent miscarriages were obtained from midwife records. Time and sex-matched births from the same records served as controls. SETTING: A Regional Hospital in Denmark. SUBJECTS: 79 singleborn women with recurrent miscarriages and 60 of their male partners comprised the main study groups. Two control groups comprised 474 female and 360 male singleborn infants who survived day 7 postpartum. MAIN OUTCOME MEASURES: Mean birthweight in the two main study groups and in subgroups with histories of 3, 4 and greater than or equal to 5 miscarriages. RESULTS: The mean birthweight of the women with recurrent miscarriages was 3265 g (SE 70) and in female controls 3414 g (SE 23) (P less than 0.025). The 17 women with five or more miscarriages had a mean birthweight of 2991 g (SD 140) (P less than 0.001 compared with controls). Of the women in the study group 10.8% were born preterm compared with 2.9% of the controls (P = 0.01). The mean birthweight of the male partners in the study group, 3470 g (SE 68), did not differ significantly from that of 3504 g (SE 31) in the male controls (P less than 0.5). CONCLUSIONS: Women suffering unexplained recurrent miscarriages have on average had a significantly lower than normal birthweight themselves, whereas this was not observed in their male partners. This points towards the existence of a birthweight-reducing trait associated with recurrent miscarriages, the trait being manifest only in the woman. PMID- 1622915 TI - Calcium homeostasis in pregnancy during long-term heparin treatment. AB - OBJECTIVE: To investigate the effect of subcutaneous heparin treatment on calcium homeostasis in pregnancy. DESIGN: A longitudinal case-control observational study. SETTING: Department of Obstetrics and Gynaecology, Karolinska Hospital, Stockholm, Sweden. SUBJECTS: 36 pregnant women with previously verified thromboembolic complications and 23 healthy pregnant control women similar in age, parity, weight, and smoking habit. INTERVENTIONS: Thromboprophylaxis during pregnancy and 6 weeks post partum was given with subcutaneous heparin twice daily to the 36 women with a history of thromboembolic complications, 16 received an average dose of 24,500 IU/day and 20 a mean dose of 17,300 IU/day. Venous blood and urine samples were obtained every 4 weeks. MAIN OUTCOME MEASURES: Serum concentrations of total calcium, ionized calcium, calcitonin and urinary calcium. RESULTS: Women on high-dose heparin treatment showed significantly higher concentrations of total and ionized calcium and of calcitonin in serum and significantly lower concentrations of calcium in urine than did 23 normal pregnant controls. The differences were most pronounced in the third trimester. The results obtained in the low-dose heparin group were between those in the high dose and the control groups. At 8 weeks postpartum there were no significant differences between the heparin-treated women and the controls. No significant differences were found during pregnancy in haematocrit, liver or renal function, serum levels of albumin, phosphate, magnesium, alkaline phosphatase, parathyroid hormone or urinary cyclic AMP. CONCLUSIONS: Heparin treatment during pregnancy results in changes in calcium homeostasis and a dose-dependent response is suggested. PMID- 1622916 TI - Vaginosonographic velocimetry in uterine arteries before and after administration of beta-mimetics. AB - OBJECTIVE: To investigate the effect of surgical procedures at 15 weeks gestation (amniocentesis or cervical cerclage), with or without post-operative ritodrine prophylaxis, on uterine blood flow velocity waveforms and maternal heart rate. DESIGN: A quasi-randomized observational study. SETTING: University Department of Obstetrics and Gynaecology, Vienna. SUBJECTS: Sixty women having a genetic amniocentesis for advanced maternal age and 57 women having elective cervical cerclage for previous preterm labour or recurrent miscarriage. INTERVENTIONS: The women in each group were allocated either to receive prophylactic ritodrine postoperatively or to receive no ritodrine treatment. Allocation used the year of birth of the woman (odd years received ritodrine, even years received no treatment). All the women had vaginal ultrasound velocimetry studies in both mainstem uterine arteries through the parametrium before the surgical procedure and again after the procedure. The ritodrine-treated women in the cerclage group received intraveneous ritodrine hydrochloride (0.2 mg/min) and those in the amniocentesis group received 60 mg ritodrine/day orally. MAIN OUTCOME MEASURES: Uterine artery blood flow velocity waveform indices: A/B ratio and pulsatility index (PI) and maternal heart rate before and after the surgical procedure. RESULTS: The only statistically significant difference in haemodynamic values between those obtained before the procedure and those obtained after the procedure with or without prophylactic ritodrine was seen in the women who had cervical cerclage with postoperative intravenous ritodrine. The mean A/B ratio decreased from 2.69 (SD 1.17) to 2.11 (SD 0.44), and the mean PI from 1.62 (SD 0.47) to 1.21 (SD 0.3) and the mean maternal heart rate increased from 82.6 (SD 11.1) to 99.4 (SD 15.7). There were no other statistically significant differences between before and after haemodynamic values. CONCLUSIONS: There are no clinically relevant effects of amniocentesis and cervical cerclage on uterine blood flow velocity waveforms. PMID- 1622917 TI - Length and variation in the menstrual cycle--a cross-sectional study from a Danish county. AB - OBJECTIVE: To investigate the current epidemiology of menstrual patterns among women of fertile age. DESIGN: Cross-sectional postal questionnaire study. SETTING: County of Copenhagen, Denmark. SUBJECTS: 3743 women, aged 15-44, selected at random from a Danish county, who were asked to provide information on menstrual pattern during the preceding year, 1981. The response rate was 78%. Information from non-responders was obtained via telephone interviews. RESULTS: In women with regular menstrual cycles, the 5th-95th centile range of usual cycle length decreased from 23-35 days in the 15-19 years age group to 23-30 days in the 40-44 years age group. Only 0.5% of regular menstruating women had a usual cycle length of less than 21 days and 0.9% had a usual cycle length of greater than 35 days. At least one cycle length of less than 21 days was experienced by 18.6%, whereas 29.5% had at least one cycle of greater than 35 days. Menstrual cycle variation of greater than 14 days was present in 29.3% of all women. Cycle length variation of greater than 14 days was 2.7 times more frequent in women from lower social groups (controlled by age). CONCLUSION: The study confirmed the normally used definitions of polymenorrhoea (cycle length less than 21 days) and oligomenorrhoea (cycle length between 36 and 90 days), as these very short or long menstrual cycle lengths were very seldom recorded for a longer period. However, the high frequency in a normal population of large menstrual cycle length variation challenges the view that an intra-individual variation of greater than 5 days should be regarded as a sign of disease in the woman. PMID- 1622918 TI - Secondary amenorrhoea: prevalence and medical contact--a cross-sectional study from a Danish county. AB - OBJECTIVE: To examine the prevalence of secondary amenorrhoea and the patterns of seeking medical advice for secondary amenorrhoea in an unselected population. DESIGN: Cross-sectional postal questionnaire study. SETTING: County of Copenhagen, Denmark. SUBJECTS: 3743 women, aged 15-44, selected at random from a Danish county who were asked to provide information on menstrual patterns for the preceding year, 1988. The response rate was 78%. Information from non-responders was obtained via telephone interviews. RESULTS: One-year period prevalence of secondary amenorrhoea of more than 3 months duration was 4.6% and was 7.6%, 3.0%, and 3.7% in women aged 15-24, 25-34, and 35-44 respectively. The duration of secondary amenorrhoea was 6 months or less in 75% aged 15-34 years, but longer than 6 months in 55% of those aged 35-44 years. A social gradient was found of the prevalence of secondary amenorrhoea (odds ratio 3.3, 95% CI 1.5-8.3) in the lowest social group compared with the highest social group; controlled by age. Only 39% of women with secondary amenorrhoea had contacted a doctor. Educational level or social status did not seem to influence the frequency of medical contact in women with amenorrhoea. CONCLUSION: Spontaneous return of the menstrual cycle occurs within 6 months in many amenorrheic women below the age of 35. The detailed investigation of secondary amenorrhoea in this age group can be postponed until it is of 6 months duration, unless there is clinical suspicion of disease. The relative infrequency with which women with secondary amenorrhoea seek medical advice constitutes an important source of selection bias in hospital based clinical research on this topic. PMID- 1622919 TI - A double-blind randomized study of the effect of erythromycin in preventing pelvic inflammatory disease after first trimester abortion. AB - OBJECTIVE: To assess the prophylactic use of erythromycin in prevention of post abortal pelvic inflammation disease (PID) in first trimester abortion. DESIGN: Double-blind, randomized controlled trial. SETTING: Department of Surgery, County Hospital, Denmark. SUBJECTS: Four hundred and thirty two women who were to undergo induced abortion before 12 weeks gestation were randomized to be treated either with prophylactic erythromycin or a placebo. INTERVENTION: The women were randomized to receive a placebo or erythromycin, 500 mg twice a day for 7 1/2 days starting the evening before the abortion. All the women were investigated for Chlamydia trachomatis and Neisseria gonorrhoea before the abortion. MAIN OUTCOME MEASURES: Frequency of cervical C. trachomatis and N. gonorrhoea and frequency of PID after abortion. RESULTS: Fifty four women were excluded after randomization. The frequency of PID was 11% (20/189) in the erythromycin group and 16% (30/189) in the placebo group (P = 0.13, chi 2-test). The prevalence of C. trachomatis was 19% (15/78) in women less than or equal to 20 years of age, 13% (14/109) in women between 21 and 25 years and 2% (5/241) in women greater than or equal to 26 years of age. In women positive for C. trachomatis erythromycin prophylaxis significantly reduced the frequency of PID to 8% (1/13) compared with 43% (6/14) in the placebo group (P = 0.051, logistic regression analysis). Erythromycin had no effect on other potential high risk groups (first pregnancy, nulliparous, less than 20 years of age, and women with previous PID). CONCLUSION: Prophylactic erythromycin is not warranted for all women having an abortion. Cervical C. trachomatis is a risk factor for postabortal PID, and prophylaxis with erythromycin significantly reduces the frequency of PID. However, only a few women with PID had cervical C. trachomatis, and the prevention of post-abortal PID remains a major challenge requiring further studies. PMID- 1622920 TI - Ovarian hyperstimulation syndrome and deep cerebral venous thrombosis. PMID- 1622921 TI - The flying squad--an expensive and potentially dangerous practice in modern obstetrics. PMID- 1622922 TI - The flying squad. Commentary. PMID- 1622923 TI - The flying squad. Commentary. PMID- 1622924 TI - The Stamey endoscopic bladder neck suspension: a clinical and urodynamic investigation, including actuarial follow-up over four years. PMID- 1622925 TI - Colposcopically directed punch biopsy: a potentially misleading investigation. PMID- 1622926 TI - Vaccine development: necessity as the mother of invention. PMID- 1622927 TI - The Y-box factors: a family of nucleic acid binding proteins conserved from Escherichia coli to man. AB - The Y-box factors interact specifically with both DNA and RNA. Biologically they have roles in both transcriptional and translational regulation. Conserved through evolution from prokaryotic to eukaryotic organisms they represent a new family of nucleic acid binding proteins. PMID- 1622928 TI - DNA damage, mutations, cancer, and aging. American Association for Cancer Research Special Conference: Cellular Responses to Environmental DNA Damage, Banff, AB, Canada, December 1-6, 1991. PMID- 1622929 TI - Cell cycle regulation of vertebrate p34cdc2 activity: identification of Thr161 as an essential in vivo phosphorylation site. AB - The protein kinase p34cdc2 is a key regulator of the cell cycle in all eukaryotes. Its activity is controlled by cell cycle-dependent interactions with other proteins, notably cyclins, and by changes in its phosphorylation state. Two inhibitory phosphorylation sites in chicken p34cdc2 have previously been mapped to threonine 14 and tyrosine 15. Here we describe the identification of threonine 161 as an additional in vivo phosphorylation site in vertebrate p34cdc2. Phosphorylation of this site is cell cycle dependent and likely to be required for p34cdc2 activity. PMID- 1622930 TI - DNA binding, multimerization, and transcription stimulation by the Xenopus Y box proteins in vitro. AB - The Y box factors bind to a specific DNA sequence (the Y box, containing a reverse CCAAT element) and have been implicated in the regulation of transcription. We have used deletion mutagenesis to define the protein domains of two Xenopus Y box factors, FRG Y1 and FRG Y2, that are essential for DNA binding, multimerization, and transcription. A domain of the Y box factors homologous to an Escherichia coli cold shock protein is required for DNA binding. Both the E. coli protein and the Y box factors recognize DNA sequences with similar selectivity. The conserved region between these proteins does not contain any previously defined DNA-binding motifs. The hydrophilic C-terminal tail of the proteins contributes to the assembly of nucleoprotein complexes. This region contains an unusual pattern of basic and acidic amino acids and represents a new type of domain mediating protein-protein interactions in transcription factors. Both the DNA-binding and the multimerization domains are important for stimulating transcription from the Xenopus hsp70 promoter in vitro. PMID- 1622931 TI - Dominant negative mutants of transcription factor mXBP (CRE-BP1, ATF-2). AB - Transcription factors of the CREB/ATF family bind to a consensus DNA sequence TGACGTCA (cyclic AMP response element) found in the promoters of numerous genes. Transcriptional activation by one of these proteins, CREB, has been extensively analyzed, but the function of the other family members is not well understood. We have analyzed the function of mXBP (CRE-BP1, ATF-2), one member of the CREB/ATF family of transcription factors. Overexpression of mXBP resulted in the transcriptional activation of a promoter containing cAMP response elements which bind mXBP. Mutagenesis of the mXBP DNA-binding domain identified residues important for binding to the cyclic AMP response element. Mutants that did not bind specifically to DNA were not able to activate transcription. Several of these mutants suppressed both DNA binding and transcriptional activation by wild type mXBP. These dominant negative mutants will be useful in further analysis of mXBP function. PMID- 1622932 TI - Multiple SP1 binding sites confer enhancer-independent, replication-activated transcription of HIV-1 and globin gene promoters. AB - We demonstrate that multiple SP1 protein:DNA binding sites confer enhancer independent activation on the HIV-1 and globin gene promoters. This activation process can be achieved either by DNA replication of the promoter-containing plasmid or by high concentrations of input plasmid DNA used in the transfections. In the case of HIV-1, the three SP1 sites adjacent to the promoters TATA box are essential for this activation process. Furthermore, the human beta globin gene, which is normally dependent on a linked enhancer for transcriptional activity, can be made enhancer independent by insertion of SP1 binding sites adjacent to its TATA box. We speculate that (SP1)n-TATA type RNA polymerase II promoters may be generally permissive when present on actively replicating DNA templates and that this property of the HIV-1 promoter may be of importance to the activation of the DNA provirus in latently infected T cells. PMID- 1622933 TI - The product of unr, the highly conserved gene upstream of N-ras, contains multiple repeats similar to the cold-shock domain (CSD), a putative DNA-binding motif. AB - We show that the open reading frame transcribed from the unr gene (immediately upstream of N-ras) in mammals consists of multiple repeats similar to the cold shock domain (CSD), a putative DNA-binding motif found in prokaryotic cold-shock proteins, and eukaryotic DNA-binding proteins. Alignment of the CSD sequences of unr with those from other proteins reveals a core of similarity for which a consistent secondary structure prediction can be derived. This prediction suggests that the CSD consists primarily of beta-sheet, in contrast to most known eukaryotic DNA-binding proteins. Sequence analysis of the 3' end of the guinea pig unr gene shows that the core of one CSD repeat is encoded in a single exon, consistent with the modular assembly of the gene from ancestral CSD-coding units. PMID- 1622934 TI - Molecular model for DNA recognition by the family of basic-helix-loop-helix zipper proteins. AB - The basic-helix-loop-helix-zipper (bHLH-Zip) motif is a conserved region of approximately 70 amino acids that mediates both sequence-specific DNA binding and protein dimerization. This motif is found in protein sequences from many eukaryotic organisms and is contained in the protein sequence of the oncogene myc and its partner max, and a shortened version of the motif (bHLH) is found in the muscle determination factor myoD and its partner E12. An evaluation of the conserved amino acids that define the motif coupled with the published mutagenic studies of this region has led to our formulation of a molecular model for the binding of this motif as a dimer to specific sequences of DNA. This model has the dimeric protein interacting with an abutted, dyad-symmetric DNA sequence. Helix 2 of each monomer is modeled as a coiled-coil extension of the C-terminal "leucine zipper." Helix 1 does not interact with helix 1 from its partner in the dimer but with the hydrophobic surface created when the helix 2 regions of the dimer interact with each other as a coiled-coil. Sequence-specific interactions are proposed between the basic region and the invariant cis elements that all bHLH Zip proteins bind. PMID- 1622935 TI - Hypothesis: is eukaryotic initiation factor 2 the scanning factor? PMID- 1622936 TI - Novel repetitive sequence motifs in the alpha and beta subunits of prenyl-protein transferases and homology of the alpha subunit to the MAD2 gene product of yeast. PMID- 1622937 TI - Cataract management. PMID- 1622938 TI - The sensitive period in infancy. PMID- 1622939 TI - Current practice of cataract extraction and anaesthesia. AB - A questionnaire regarding preferred methods of cataract extraction and anaesthesia was sent to 456 consultant ophthalmologists in England and Wales. Replies were received from 86% (n = 392), 83% (n = 380) having completed the questionnaire in full. The most frequently employed surgical approach was non automated extracapsular cataract extraction. Only 2% of surgeons (n = 8) used phacoemulsification routinely and 2% (n = 7) used intracapsular extraction. Intraocular lens implantation was the standard practice of 99% of surgeons (n = 376). There has been a dramatic increase in the popularity of local anaesthesia, which was employed routinely (in more than three-quarters of their cases) by 20% of surgeons (n = 76). Retrobulbar infiltration remains the most common method of administration. Sedation was given routinely by 45% of surgeons (n = 171) when using local anaesthesia. Medical contraindications and patient preference were considered the most important reasons for selecting local anaesthesia rather than general. The exclusive use of general anaesthesia in cataract surgery appears to be diminishing. PMID- 1622940 TI - Clinical evidence for the onset of the sensitive period in infancy. AB - Seven neonates had a IIIrd or VIth nerve palsy or afferent visual pathway pathology at birth. These abnormalities resolved within 6 weeks and the children have developed normal visual acuity, motor fusion, and stereopsis. We conclude that there is a latent period of 6 weeks before the onset of the sensitive period. PMID- 1622941 TI - Sequential argon-YAG laser iridotomies in dark irides. AB - Laser iridotomies in dark coloured irides are associated with higher complication and failure rates. A prospective clinical study to evaluate the use of the argon and Nd:YAG laser in sequential combination for iridotomy was carried out on 20 eyes of 13 patients with dark irides. Patent iridotomies were achieved in single treatment sessions for all the eyes. Iridotomy closure was observed in one eye during a mean follow-up period of 14 months (range 6-20 months). Complications from the treatment occurred in five eyes and were minor. Total mean energy used for the argon and Nd:YAG stages respectively were a third of most studies on pure argon and Nd:YAG iridotomies. Sequential argon-YAG laser iridotomy combines most of the advantages of both laser types while avoiding some of their disadvantages. We find it a safe and effective tool for iridotomy in otherwise difficult dark irides. PMID- 1622942 TI - Dapsone therapy for the acute inflammatory phase of ocular pemphigoid. AB - Oral dapsone was used to treat five patients who presented in the acute inflammatory phase of ocular pemphigoid. The diagnosis was made clinically by identifying cicatricial changes which were in some cases difficult to find. In all cases it was the inflammatory rather than the cicatricial features which responded to treatment. An initial dose of 100 mg/day was effective without toxicity. When 150 mg/day was used patients experienced side effects. A clinical response was obtained after 1-4 weeks and could be maintained on a dose of between 50 mg on alternate days and 100 mg/day. Therapy was withdrawn during remissions which lasted up to 32 weeks but all cases required continuing therapy which has remained effective. Immunopathological examination was carried out on two occasions in all cases and although positive on at least one occasion the results did not correlate with disease activity or treatment. The inflammatory phase of ocular pemphigoid should be added to the list of diseases responsive to dapsone. PMID- 1622943 TI - Diffractive multifocal intraocular lens implants for unilateral cataracts in prepresbyopic patients. AB - Multifocal intraocular lenses allow pseudophakic patients to obtain good near and distance visual acuities without an additional near correction. We report our experiences in implanting diffractive multifocal intraocular lenses in prepresbyopic patients with acquired unilateral cataracts and assess their postoperative visual acuities and stereoscopic vision. Accommodative function in patients following cataract surgery is discussed. PMID- 1622944 TI - Synthesis of interleukin-1 and prostaglandin E2 by lens epithelial cells of human cataracts. AB - To test our hypothesis that pseudophakic inflammation, including the fibrin reaction, may be caused by cytokines, prostaglandins (PG), or both, synthesised by residual lens epithelial cells (LECs), we measured interleukin-1 alpha (IL-1 alpha) and PGE2 in the incubation medium of cultures of human LECs obtained by capsulotomy during cataract surgery. After 1 week radioimmunoassay showed that there were 1.46 (0.62) ng of PGE2/10(6) cells (mean (SD) six cultures), and after 4 weeks, there were 5.50 (2.20) ng of PGE2/10(6) cells (seven cultures). During culture the cells proliferated and underwent fibroblast-like cell changes on exposure to the plastic of the wells. In the medium of control plates to which sodium diclofenac had been added PGE2 was not detected. Some IL-1 alpha was found in four of 10 samples, each of which contained media from 12 cultures; 207 pg/10(6) cells in one of the two pools of 2-week cultures, 120 pg/10(6) cells in one pool and 139 pg/10(6) cells in another of the three pools of 3-week cultures, and 111 pg/10(6) cells in the one pool of 4-week cultures. PGE2 and IL-1 alpha may therefore be produced in vivo by residual LECs after cataract surgery, and may be involved in postoperative inflammation, including the fibrin reaction. PMID- 1622945 TI - Outcome of strabismus surgery in congenital esotropia. AB - The results of squint surgery in 40 children with congenital esotropia are analysed. A 'favourable outcome' was achieved in 23 (57.5%) children. The factors affecting the final outcome including ocular alignment in the immediate postoperative period, age at the time of surgery, amblyopia, associated inferior oblique overaction, dissociated vertical deviation, latent or manifest latent nystagmus, and the surgical procedures used are discussed. PMID- 1622946 TI - Full thickness macular breaks in rhegmatogenous retinal detachment with peripheral retinal breaks. AB - Between 1975 and 1989, 11 eyes were treated for retinal detachments with both peripheral and full thickness macular breaks. Long term retinal reattachment was dependent on successful closure of peripheral retinal breaks. Direct treatment of the macular break was necessary in only one case, which redetached 3 months after vitrectomy. Vitrectomy is not the initial treatment of choice for uncomplicated retinal detachments with both peripheral and full thickness macular breaks, unless required for the closure of the peripheral retinal breaks. PMID- 1622947 TI - Management of traumatic optic neuropathy--a study of 23 patients. AB - Twenty three patients with traumatic optic neuropathy were managed by medical and surgical treatment as follows. High dose intravenous steroids were initiated in all patients. If visions did not improve significantly after 24 to 48 hours decompression of an optic nerve sheath haematoma by medial orbitotomy and neurosurgical decompression of the optic canal were considered based on computed tomographic scan findings. Nine of 16 patients who received steroids only showed significant improvement. One of three showed improvement on optic nerve decompression after steroid failure; three or four showed improvement on optic nerve decompression after steroid failure; three or four showed improvement with combined optic nerve sheath decompression by the medial orbitotomy and decompression of the optic canal by frontal craniotomy. A lucid interval of vision after injury and an enlarged optic nerve sheath were associated with an improved prognosis. Five of the 23 patients had a lucid interval and all five had a final improved vision, while only five of 18 patients without a lucid interval improved. Similarly seven of the nine with an enlarged optic nerve sheath showed improvement while only three of 10 patients (three bilateral cases) who presented with no light perception improved with medical and surgical treatment. While a prospective controlled study of the management of traumatic optic neuropathy is necessary this preliminary study suggests that treatment of traumatic optic nerve sheath haematoma by optic nerve sheath decompression should be considered in selected patients. PMID- 1622948 TI - Modification of trabeculectomy to avoid postoperative hyphaema. The 'guarded anterior fistula' operation. AB - The effect of varying the position of a trabeculectomy fistula on the rate of postoperative hyphaema was studied in a prospective randomised trial. One eye of each of 78 consecutive patients with primary open angle glaucoma and exfoliation glaucoma was allocated to one of two groups. In group A the fistula was fashioned anterior to the scleral spur, entirely in corneal tissue. In group B the fistula included cornea and sclera with trabecular meshwork and scleral spur. Seven out of 39 eyes (18%) in group A developed a postoperative hyphaema with detectable blood level, compared with 22 out of 39 eyes (56%) for group B (p less than 0.001). In addition, the severity of the bleeding was greater in group B, and the three cases of recurrent bleeding were all in this group. Group B patients remained in hospital for an average of 3.9 days, which was significantly longer (p = 0.004) than the average of 2.9 days for group A. This difference was related to the frequency and severity of the hyphaema. The type of dissection or the occurrence of hyphaema did not influence the intraocular pressure at 4 months after surgery. PMID- 1622950 TI - Nasal and orbital recurrence of conjunctival melanoma 21 years after exenteration. AB - In our experience 5% of invasive malignant melanomas of the conjunctiva arising from areas of primary acquired melanosis with atypia spread to the ipsilateral nasal cavity and paranasal sinuses. Twenty one years after orbital exenteration for multicentric conjunctival melanoma an 82-year-old man was seen with an orbital recurrence, which had extended to the nasal cavity and paranasal sinuses through the nasolacrimal duct without invading the mucosa. This previously undescribed way of spread after the longest symptom-free interval following exenteration ever reported is illustrated. PMID- 1622949 TI - Microwave plaque thermoradiotherapy for choroidal melanoma. AB - Microwave thermoradiotherapy was used as a primary treatment for 44 patients with choroidal melanoma. An episcleral dish-shaped microwave antenna was placed beneath the tumour at the time of plaque brachytherapy. While temperatures were measured at the sclera, the tumour's apex was targeted to receive a minimum of 42 degrees C for 45 minutes. In addition, the patients received full or reduced doses of plaque radiotherapy. No patients have been lost to follow-up. Two eyes have been enucleated: one for rubeotic glaucoma, and one for uveitic glaucoma. Though six patients have died, only one death was due to metastatic choroidal melanoma (39 months after treatment). Clinical observations suggest that the addition of microwave heating to plaque radiation therapy of choroidal melanoma has been well tolerated. There has been a 97.7% local control rate (with a mean follow-up of 22.2 months). We have reduced the minimum tumour radiation dose (apex dose) to levels used for thermoradiotherapy of cutaneous melanomas (50 Gy/5000 rad). Within the range of this follow-up period no adverse effects which might preclude the use of this microwave heat delivery system for treatment of choroidal melanoma have been noted. PMID- 1622951 TI - Pseudopapilloedema in the linear naevus syndrome. AB - This case report describes the ophthalmic findings in a child with the linear naevus syndrome. The patient was referred by the Department of Paediatric Neurology with 'unilateral papilloedema'. This was thought to be a form of pseudopapilloedema, a finding that has not been previously described in this syndrome. PMID- 1622952 TI - Fundus albipunctatus associated with cone dystrophy. AB - We describe five unrelated patients in whom the typical signs of fundus albipunctatus were accompanied by colour vision defects, bull's eye or similar macular lesions, and severely diminished full-field cone electroretinograms indicating widespread damage to cones outside the macula. All patients had noticed night blindness from childhood. Signs of retinitis punctata albescens, a disease of similar appearance but with characteristics resembling retinitis pigmentosa, were absent. We cannot be sure whether these patients represent a process of fundus albipunctatus or a distinct disease entity or a casual combination of fundus albipunctatus and cone dystrophy. PMID- 1622954 TI - Alternative method for laser treatment of superior retinal tears in eyes with gas tamponade. PMID- 1622953 TI - Titanium tetrachloride burns to the eye. AB - We present eight cases of chemical burns of the eyes from titanium tetrachloride, an acidic corrosive liquid. However it causes severe chemical burns which have a protracted course and features more akin to severe alkali burns. Injuries related to titanium tetrachloride should be treated seriously and accordingly appropriate management is suggested. PMID- 1622955 TI - Workload in oral and maxillofacial surgery: analysis of time trends from linked statistics in a defined population. AB - Data from the Oxford Region were used to study trends in hospital admission rates and demographic profiles of hospital care in the National Health Service in oral and maxillofacial surgery. In a defined population of 1.9 million people, admission rates for inpatient care, day case care, and outpatient attendance rates all almost doubled between 1975-1985. Population-based age-specific admission rates were much higher in teenagers and young adults than in other age groups. In these age-groups admission rates for females were about double those for males. Whilst perhaps not surprising to the oral and maxillofacial surgeon, these demographic profiles of workload are strikingly different from those found in most other hospital specialties. PMID- 1622956 TI - The use of mandibular symphyseal bone in maxillofacial surgery. AB - Mandibular symphyseal bone (MSB) is useful in alveolar cleft grafting and orthognathic surgery. This paper reports on the application and techniques using MSB. PMID- 1622957 TI - Topical application of 5% eutectic mixture of lignocaine and prilocaine (EMLA) before removal of arch bars. AB - The analgesic effect of topical application of a 5% eutectic mixture of lignocaine and prilocaine (EMLA) was studied in 45 patients undergoing removal of oral arch bars used for the treatment of mandibular fractures. Employing a double blind technique, either 4 g of the eutectic mixture (EMLA group, n = 15) or 4 g of a similar emulsion containing no local anaesthetic (placebo group, n = 15) was applied to the gingivae using a toothbrush and a standardised technique. In the control group (n = 15), infiltration anaesthesia with lignocaine was used only if requested by the patient during the removal of the arch bars. The patients in the EMLA group had significantly better analgesia (P less than 0.005) of the gingivae just before removal of the arch bars than patients in the placebo group, but by the end of the procedure the difference in analgesia was not significant. The number of patients who found the procedure pain-free was significantly higher in the EMLA group (7/14) than in the placebo group (2/15) (P less than 0.005). The plasma concentrations of both lignocaine and prilocaine were well below the toxic levels. Topical application of EMLA can be recommended for short procedures as an alternative to infiltration. PMID- 1622958 TI - A prospective study of 134 consecutive patients requiring diagnosis, excision and repair of a facial cutaneous lesion. AB - A prospective study of 134 patients undergoing excision of a facial lesion was undertaken. Considerable clinical diagnostic difficulty was experienced, with 21% of clinical diagnoses being incorrect. A tendency towards a clinical over diagnosis of basal cell carcinoma was noted and whilst this is not unreasonable, a number of benign lesions inevitably were diagnosed as malignant with unnecessary sacrifice of tissue. Incisional biopsy of lesions should be considered when sited close to important anatomical structures to enable accurate diagnosis prior to definitive surgery. Although a few definite indications for a particular reconstructive technique exist (Table 1), a choice is more often available. Repair of the excisional defect with a local flap as opposed to a skin graft resulted in a reduced length of hospital admission with fewer postoperative complications and better final cosmesis. As a consequence, a local flap is recommended as the method of repair where direct closure is not feasible. PMID- 1622959 TI - Oral carcinoma in pregnancy. AB - Oral cancer presenting in pregnancy is a rare combination which, because of current epidemiological changes in the disease, may present more often in the future. Treatment of the condition can be very difficult. Decisions have to be made about terminating the pregnancy or finding a balance between the treatment of the mother and protecting the foetus from the effects of various treatment modalities. This may result in a compromise treatment of the disease. To illustrate the problems, we discuss a case of carcinoma of the tongue presenting in a 23-week pregnant Gravida 1 Para 0 lady, and review the literature. PMID- 1622960 TI - Gram negative aerobic bacillus pneumonia in oral and maxillofacial surgery--a case for comment. AB - A case illustrating the potentially fatal complication of endogenous Gram Negative Aerobic Bacillus (GNAB) septicaemia secondary to nosocomial pneumonia is presented along with current theories as to its aetiology. The technique of selective decontamination of the digestive tract is designed and advocated to prevent such occurrences; oral and maxillofacial surgeons should be aware of this approach. It may be, however, that by using much simpler manoeuvres such as changes in policy regarding gastric stress ulcer prophylaxis, the already small risk of such an occurrence will be further reduced. Awareness of this condition will allow a higher index of suspicion when presented with catastrophic septic complications on the ITU and aid in more rational planning of antimicrobial therapy. PMID- 1622961 TI - Orbital lymphoma: blindness as a presenting symptom. AB - A case of isolated orbital lymphoma presenting as blindness is reported. An unusual feature of bone erosion is highlighted and the difficulty in the histological interpretation is discussed. PMID- 1622962 TI - Effects of bilateral jugular vein ligation on intracranial pressure and cerebrospinal fluid outflow resistance in cats. AB - In order to study the effect of jugular venous outflow obstruction on intracranial pressure and cerebrospinal fluid (CSF) reabsorption capability, changes in epidural pressure (EDP) and CSF outflow resistance (Ro) were examined following bilateral jugular vein ligation in cats. EDP increased significantly (P less than 0.01) immediately after ligation from the control value of 4.9 +/- 0.5 mmHg (mean +/- SEM) to 15.9 +/- 0.9 mmHg. Thereafter, EDP gradually decreased back toward the control value. The pressure level had decreased to 6.7 +/- 0.5 mmHg by 20 minutes after ligation. The mean Ro was significantly (P less than 0.01) higher in the ligation group (200.4 +/- 9.7 mmHg/ml/min) that in the non ligation group (120.0 +/- 9.9 mmHg/ml/min). These results suggest that bilateral jugular vein ligation impairs CSF reabsorption. PMID- 1622963 TI - The caudal mandibular reconstruction plate: a radiographic and histologic study of an autopsy specimen. AB - During autopsy, a reconstructed partial mandibular resection was recovered and subjected to histological examination. The mandible had been reconstructed 12 weeks earlier with a caudal plate and autologous cancellous bone from the iliac crest. Undecalcified microsections showed that the plate was firmly anchored by screws on both sides and on one side there was bony union. However, most of the free transplant bone had undergone 'unreplaced resorption.' Nevertheless, this method offers advantages over the conventional method of seating the plate on the buccal aspect and has interesting potential for further development. PMID- 1622964 TI - An evaluation of bone healing in cavities in the jaws implanted with a collagen matrix. AB - Bony defects in the jaws after surgery may show poor healing especially in the maxilla and the area may never completely be replaced by bone. 50 patients with pathological bony cavities in the jaws were used to assess the efficacy of a collagen matrix implanted into the treated bony defect and 50 patients in whom no material was implanted were used as controls. The results were assessed radiographically at 3, 6 and 12 months. At 3 months, bone deposition in the control group was in advance of the implanted group, but after 6 and 12 months healing appeared to be similar in both groups. No adverse effects were found due to the presence of the collagen implant. Collagen delayed the early osteogenic healing period, indicating that only when it has been resorbed can the area heal with osteogenic granulation tissue. As some radiolucent areas still remained in the healed implant group after 12 months it must be assumed that the collagen implant has only been replaced by host fibrous tissue and therefore does not possess osteoinductive properties. PMID- 1622965 TI - Report of an audit into third molar exodontia. AB - A postal audit of the main surgical variables in third molar exodontia under general anaesthesia was undertaken on consultants holding a National Health contract within the British Isles. This first paper presents the results. A response rate of 175 returned questionnaires from the 247 consultants was obtained (70.9%). Analysis revealed that the majority of consultants use antibiotics, mouthwashes, sutures, analgesics and postoperative review and the minority steroids and peroperative local anaesthetic, routinely in the majority of cases. Approximately half routinely use a chisel as opposed to a bur for bone removal. The consultants who gave all their patients steroids were significantly (p less than 0.01) more likely to possess a medical qualification than the consultants who did not. PMID- 1622966 TI - Complications of use of carbon fibre in the temporomandibular joint: a case report. AB - The aetiology of recurrent temporomandibular joint dislocation is numerous. A case is described of frequent dislocation which was finally treated using a carbon fibre sling. However this was removed 3 years later due to the presence of a radiolucency in the head of the condyle. Radiographic and photographic appearances of this carbon fibre induced radiolucency are shown. PMID- 1622967 TI - Intra-masseteric actinomycosis: report of a case. AB - A case of actinomycosis arising within the masseter following extraction of a lower second molar is reported. The most likely cause was a needle tract infection from the planned administration of the local anaesthetic. PMID- 1622968 TI - Intramuscular haemangioma of the orbicularis oris muscle. AB - The intramuscular haemangioma is a relatively uncommon benign vascular tumour which accounts for less than 1% of all haemangiomas. It is a rare lesion in the orofacial muscles. A case is reported arising in the orbicularis oris muscle presenting in a 9-month-old child. PMID- 1622969 TI - A modified arch bar for use in patients with anterior crowns or bridgework. PMID- 1622970 TI - Our experiences with monocortical wire osteosynthesis in the treatment of mandibular angle fractures. PMID- 1622971 TI - A central venous catheter complicating head and neck surgery. PMID- 1622973 TI - The ethics of peer review. PMID- 1622972 TI - Cancrum oris-like lesions. PMID- 1622974 TI - Studies of method of conserving grass herbage and frequency of feeding in cattle. 1. Voluntary feed intake, digestion and rate of passage. AB - The effect of method of conserving grass herbage and the frequency of feeding on digestion in and passage from the rumen was studied in growing cattle. A single sward of perennial ryegrass (Lolium perenne cv. Endura) was cut on 1 d and conserved as silage or hay. These forages were offered as the only feed to twelve rumen-cannulated Friesian steers (average initial live weight (LW) 128 kg) either at a restricted level of intake (20 g dry matter (DM)/kg LW; Expt 1) or ad lib. (Expt 2). In Expt 1 the forages were offered either once or eight times daily. When fed once or eight times daily, in vivo digestibility of DM was very similar for hay and silage (0.771 and 0.783 respectively), while the fractional rate of digestion measured by incubation in Dacron bags was significantly (P less than 0.05) higher for silage (0.069) than hay (0.057). The rate of passage of mordanted feed out of the rumen was significantly (P less than 0.01) faster for silage when determined from concentrations of marker in the rumen (0.034 v. 0.028/h). The volume of liquid in the rumen was lower (P less than 0.01) for animals consuming silage (27.51) compared with hay (37.11), while the fractional rate of passage of liquid from the rumen was higher (0.141 v. 0.098/h, P less than 0.05). The volume of liquid in the rumen was also lower (P less than 0.05) in steers offered feed eight times daily (29.5 l), compared with once daily (35.1 l), but frequency of feeding had no significant effect either on total digestibility or on rate of digestion in the rumen. The ad lib. intake of silage was significantly (P less than 0.01) lower than that of hay (4.53 v. 5.16 kg DM/d) in Expt 2. PMID- 1622975 TI - Studies of method of conserving grass herbage and frequency of feeding in cattle. 2. Eating behaviour, rumen motility and rumen fill. AB - The influence of the method of conserving grass herbage and the frequency of feeding on eating behaviour, rumen motility and rumen fill was studied in growing steers. Silage and hay were offered to twelve rumen-cannulated Friesian steers (average initial live weight (LW) 128 kg) at a restricted level of intake (20 g dry matter (DM)/kg LW) either once or eight times daily. With once daily feeding, the daily intake of hay was consumed in a single large meal which lasted about 2 h, while silage was eaten in many small meals throughout the day. The proportion of the day spent ruminating was higher (0.39) for steers offered hay once daily than for those offered silage (0.28) or hay eight times per day (0.29). There was little effect of conservation method on frequency of rumen contraction, but contractile intensity (integration of frequency and amplitude) increased during the second half of the 24 h feeding cycle in steers offered hay either once daily or eight times daily, while the same effect was only observed when silage was offered once daily. Total daily contractile activity (the integration of the frequency and duration of myoelectric spike bursts) was significantly (P less than 0.05) higher in steers offered hay, compared with silage, once daily. The mean weight of organic matter in the reticulo-rumen of steers offered hay was significantly higher than for silage both with once (1593 v. 1326 g organic matter (OM)/100 kg LW, P less than 0.01) and eight (1367 v. 1160 g OM/100 kg LW, P less than 0.05) times daily feeding. The proportion of the particulate pool which was present as small (less than 1.2 mm) particles was always greater than 0.60. PMID- 1622976 TI - The effect of forage and forage-concentrate diets on rumen fermentation and metabolism of nutrients by the mesenteric- and portal-drained viscera in growing steers. AB - Growing Friesian steers chronically catheterized in the anterior mesenteric and portal veins were used to study the influence of feeding with either a forage or forage-concentrate diet on nutrient utilization by mucosal tissue. When animals were consuming the forage-concentrate diet the molar proportion of propionate in rumen fluid was significantly increased, although production rate as measured by isotope dilution was not altered. Net rates of absorption of VFA into portal blood when compared with rumen production rates underlined the extent to which metabolism within mucosal tissue modifies the propionate supply to the liver. Net glucose utilization by splanchnic tissue was shown to be significantly lower on the forage-concentrate diet. There were no effects of diet on whole-body glucose turnover or on the proportion of glucose derived from propionate. Animals fed on the forage-concentrate diet had significantly lower concentrations of circulating essential amino acids, due mainly to a reduction in branched-chain amino acid levels. There was net absorption of all amino acids by animals on both diets except for glutamate, glutamine and taurine in forage-fed animals. PMID- 1622977 TI - Influence of the amount of starch on the glycaemic index to rice in non-insulin dependent diabetic subjects. AB - To test whether the glycaemic index is altered by the amount of carbohydrate, meals containing 25 and 50 g carbohydrate as white rice and white bread were taken by seven non-insulin-dependent diabetic subjects. The glycaemic indices to parboiled white rice corresponding to 25 and 50 g carbohydrate were similar, being 55 (SE 10) and 60 (SE 8) respectively. The incremental areas of blood glucose (above basal) to parboiled white rice were significantly lower than to white bread after both an amount corresponding to 25 g carbohydrate (85 (SE 24) mM x 180 min v. 181 (SE 55) mM x 180 min; P less than 0.01) and to 50 g carbohydrate 226 (SE 29) mM x 180 min v. 423 (SE 76) mM x 180 min; P less than 0.01). Similar insulin response areas to 25 g carbohydrate given as parboiled white rice and white bread were found, whereas 50 g carbohydrate as white bread caused a significantly higher insulin response area than parboiled white rice (P less than 0.05). In conclusion, the glycaemic index of parboiled white rice is not affected by the amount of carbohydrate ingested, at least under the present study conditions. PMID- 1622978 TI - Influence of amount of dietary fat and protein on esterase-1 (ES-1) activities of plasma and small intestine in rats. AB - The objective of the present study was to characterize nutritionally esterase-1 (ES-1). For this purpose, the effects of replacement of dietary carbohydrates by isoenergetic amounts of either fat or protein on ES-1 activities of plasma and small intestine were studied in male rats. Purified diets differing in the amounts of maize starch plus dextrose, casein and various types of fat were used. Plasma and jejunal ES-1 activities were found to be increased with increasing fat intakes. As to the type of fat, increasing plasma ES-1 activities were induced by coconut fat, olive oil, maize oil and medium-chain triacylglycerols, in this order. Maize oil induced higher jejunal ES-1 activities than coconut fat and olive oil, but had similar effects to medium-chain triacylglycerols. Maize oil was more powerful in increasing plasma ES-1 activity than isoenergetic amounts of casein, but with respect to jejunal ES-1 activity these dietary components were equally effective. It is concluded that the amounts of fat and protein in the diet are important determinants of ES-1 activities in plasma and jejunum. PMID- 1622979 TI - Muscle protein degradation assessed by Nt-methylhistidine excretion in mature White Leghorn, dwarf broiler and normal broiler males maintained on either low- or high-protein diets. AB - Protein degradation rates were assessed by the excretion of Nt-methylhistidine (NtMH) in four strains of mature chickens, two White Leghorns and two broilers (dwarf and normal), fed on diets containing two levels of dietary protein. Over 0.9 of labelled NtMH was recovered within 7 d of injection from three White Leghorn, three dwarf and three normal broiler males. Protein degradation, measured by NtMH output, was related to adult body-weight by the power 0.71 and strain intercepts were significantly different. Strain differences disappeared when the rate of output of NtMH per unit lean was evaluated. The rate of output of NtMH per unit muscle was higher in birds fed on a low-protein diet of 100 g crude protein (nitrogen x 6.25; CP)/kg compared with males fed on 150 g CP/kg. It was concluded that the lower rate of protein degradation in broiler compared with layer strains at young ages is related to increased adult body-weight in agreement with well-established biological principles. PMID- 1622980 TI - The availability of lysine in diets for pigs: comparative methodology. AB - Four experiments were conducted to compare different methods for estimating the availability of lysine in protein feeds. The same feeds were used in all experiments. In the first experiment the apparent digestibility of lysine to the ileum of growing pigs was found to be 0.92, 0.69, 0.73, 0.85, 0.84 and 0.97 for soya-bean meal, cottonseed meal 1, cottonseed meal 2, meat meal, sunflower meal and skim milk respectively. In the second experiment the utilization of lysine (relative to free lysine) for weight gain, as measured in weaner pigs, was found to be 0.68, 0.73, 0.81, 0.86 and 1.00 for cottonseed meal 1, cottonseed meal 2, meat meal, sunflower meal and skim milk respectively. In Expt 3 diets were formulated to contain soya-bean meal, sunflower meal or cottonseed meal 2 with the same available lysine content from the measurements made in Expts 1 and 2. The feed conversion ratios of weaner pigs given these diets were similar for the three sources of protein when the values were adjusted for the differences in digestible dry matter intake. In the fourth experiment isoenergetic and isonitrogenous diets were formulated with increasing amounts of lysine from synthetic lysine or cottonseed meal 2. The diets were given to weaner pigs and resulted in a curvilinear response to lysine particularly for the cottonseed meal, so that the availability of lysine in cottonseed meal was similar to that of synthetic lysine at low lysine intakes and much lower than synthetic lysine at higher lysine intakes. Possible reasons for the curvilinear responses are discussed. PMID- 1622981 TI - Zinc absorption in adult men from a chicken sandwich made with white or wholemeal bread, measured by a double-label stable-isotope technique. AB - Eleven fasted adult men consumed a chicken meat sandwich made with white or wholemeal bread, extrinsically labelled with 2 mg 67Zn, on two different occasions. Immediately after eating the sandwich they were given an intravenous injection of 1.5 mg 70Zn. True Zn absorption (which was approximately 7% higher than apparent absorption) was determined by the faecal balance technique by making an allowance for endogenous excretion from measurements of faecal excretion of 70Zn. There was no significant difference in mean true Zn absorption from the white or wholemeal bread sandwich, 33.6 and 25.4% respectively. It was concluded that the substitution of wholemeal for white bread does not reduce Zn absorption from meat-based sandwiches. PMID- 1622982 TI - Calcium and phosphorus requirements of the very young turkey as determined by response surface analysis. AB - The first experiment was a central composite rotatable design with calculated calcium levels of 6.2, 7.0, 9.0, 11.0, and 11.8 g/kg diet and total phosphorus levels of 5.2, 6.0, 8.0, 10.0, and 10.8 g/kg diet (2.8 g phytin-P/kg by analysis). This design involved three replicates for each rotatable point and fifteen replicates of the central point. The second experiment was a 4 x 4 factorial design with calculated Ca levels of 8.0, 10.0, 12.0, and 14.0 g/kg diet and calculated total P levels of 7.0, 9.0, 11.0, and 13.0 g/kg diet (2.5 g phytin P/kg by analysis). There were four replicates for each treatment. In both 16 d experiments maize-soya-bean diets were used and each replicate consisted of one pen containing 10-d-old broad-breasted, white tom turkeys. The Ca and total P requirements for optimum growth were estimated to be 12.5 and 10.0 g/kg diet respectively. Bone ash was adequate at these levels of Ca and total P, but maximum bone ash was not achieved until much higher levels of Ca and total P were employed. At the required levels of Ca and total P for growth the incidences of Ca- and P-deficiency rickets were very low. There were no treatment effects on feed efficiency. Increasing dietary Ca decreased the incidence of the Ca deficiency lesion. There was a quadratic response due to dietary total P on both P-deficiency rickets and plasma dialysable P; intermediate levels of dietary P resulted in low incidence of the P-deficiency lesion and high levels of plasma dialysable P. There was a strong negative correlation between the incidence of P deficiency rickets and plasma dialysable P. Percentage retention was very low at high levels of dietary P and low levels of Ca which corresponded with slightly higher P-deficiency rickets and low plasma dialysable P. No such obvious relationships existed between Ca retention, incidence of Ca-deficiency rickets, and plasma Ca. The incidence of tibial dyschondroplasia was very low in the present study. There were pronounced dietary treatment effects on phytin-P retention; at 14 d percentage phytin-P retention treatment means ranged from 18 to 46 in Expt 1 and from 0 to 40 in Expt 2 with the highest retention of phytin-P at low levels at both Ca and total P. PMID- 1622983 TI - Application of selective extraction to the study of iron species present in diet and rat gastrointestinal tract contents. AB - Iron speciation in rodent diet and rat gastrointestinal tract lumen during dietary digestion and absorption was investigated with a novel selective extraction technique. Five Fe fractions were identified, namely exchangeable (soluble in 1 M-magnesium chloride), carbonate-bound (soluble in mild acid), oxide-bound (soluble in hydroxylamine-acetic acid), organic-bound (soluble after treatment with peroxide in nitric acid) and residual. Fe from the pelleted diet was mobilized by rat stomach to the exchangeable fraction, then redistributed to the carbonate- and oxide-bound fractions on passage through the proximal small intestine. In vitro incubation of diet with hydrochloric acid failed to mimic the in vivo effect of the stomach. In vitro neutralization of stomach contents with bicarbonate was found to produce a similar effect on Fe speciation to that seen when diet passed the proximal small intestine in vivo. Comparison of 59Fe speciation in extrinsically labelled diet with endogenous Fe speciation showed that extrinsic labelling does not uniformly label all endogenous species. The experiments suggest that selective extraction may provide a useful approach to the study of Fe species present in diets, in vitro digestions and gastrointestinal contents. PMID- 1622984 TI - Tissue alpha-tocopherol status during late fetal and early neonatal life of the guinea-pig. AB - The alpha-tocopherol content of a number of different fetal, neonatal and maternal guinea-pig tissues was determined and compared with plasma and erythrocyte alpha-tocopherol values. During late gestation, the fetal liver appears to act as a storage site for alpha-tocopherol, the majority of which is released immediately following birth. In contrast, lung and brain vitamin E levels are relatively constant over the final period of gestation and during early neonatal life. The ontogeny of alpha-tocopherol in brain and lung was similar to that for erythrocytes while plasma alpha-tocopherol content varied considerably and did not accurately reflect tissue alpha-tocopherol status. Surprisingly, fetal and maternal lung alpha-tocopherol concentrations were similar at all time-points considered, whereas fetal liver alpha-tocopherol status was always considerably greater than maternal liver alpha-tocopherol content. These results, if representative of the human fetus, suggest that preterm infants may not have tissue alpha-tocopherol concentrations as low as previously assumed and that during the perinatal period erythrocyte alpha tocopherol content is a more accurate indicator of tissue alpha-tocopherol concentration than plasma alpha-tocopherol content. PMID- 1622985 TI - Digestion of complex carbohydrates and large bowel fermentation in rats fed on raw and cooked peas (Pisum sativum). AB - Rats were fed on four semi-purified diets in which raw or cooked peas (Pisum sativum var. Sentinel) provided 250 or 500 g/kg diet. Pressure-cooking of peas followed by rapid freezing and freeze-drying increased the proportion of starch resistant to alpha-amylase (EC 3.2.1.1) without previous treatment with dimethyl sulphoxide. There were only minor effects of cooking on the digestibilities of non-starch polysaccharides and their constituent sugars. With the higher dietary pea concentration there were marked increases in the flow of organic matter to, and fermentation in, the large bowel. These increases were associated with significant increases in colonic tissue and contents weights, and in colonic transit time. Both cooking and dietary pea inclusion rate altered the pattern of volatile fatty acids in caecal contents and in portal blood. PMID- 1622987 TI - Transplant coronary artery disease. PMID- 1622986 TI - The effects of acute and chronic administration of n-6 and n-3 polyunsaturated fatty acids on ethanol-induced gastric haemorrhage in rats. AB - Female weanling rats in three equal groups (n 12) were given orally by intubation 1 ml micellar solution of taurocholic acid (10 mM) and either arachidonic acid (20:4 n-6), linoleic acid (18:2 n-6) or eicosapentaenoic acid (20:5 n-3) at a concentration of 120 mM. After 1 h the rats were given intragastrically 2 ml absolute ethanol and were killed 1 h later. Rats given oral 20:4 n-6 showed a significant reduction (P less than 0.05) in the extent (%) of gastric mucosal haemorrhage compared with either the rats given 20:5 n-3 or 18:2 n-6 (8.3 (SD 7.3), 23.2 (SD 10.4) and 21.4 (SD 10.4) respectively. In a second experiment, four equal groups (n 12) of female Wistar rats were fed for 5 weeks on either a control diet of standard laboratory rat food, or the same diet enriched with either maize oil or fish oil or butterfat at a level of 100 g/kg. Following a 24 h fast the rats received an intragastric dose of 2 ml ethanol and were killed 1 h later. Examination of the extent (%) of gastric lesion showed a significant reduction (P less than 0.05) with the feeding of either maize oil or fish oil compared with the controls (12.2 (SD 8.2), 15.3 (SD 13.2) and 29.3 (SD 14.0) respectively). The butterfat diet was not significantly different from the control diet (23.8 (SD 8.1)). PMID- 1622988 TI - Graft atherosclerosis: effects of cellular rejection and human lymphocyte antigen. AB - Graft atherosclerosis after heart transplantation is a problem that may limit long-term survival. The objective of this study was to establish whether an association exists between graft atherosclerosis, cellular rejection, HLA compatibility, or antilymphocyte antibodies in recipient serum. Results of cineangiograms from 306 recipients were available. Life table and logistic regression analysis identified only a significant effect of cellular rejection on development of angiogram-evident graft vessel disease. A total of 146 allografts obtained at another transplantation or autopsy were also available. Coronary vessel narrowing was measured by planimetry. Linear regression with coronary narrowing as dependent variable established a positive association with history of cellular rejection. No effect was documented for panel reactive antibody level obtained before or after transplantation. We also did not show an impact of HLA mismatch on this process. The lack of HLA antigen effect prompts us to be cautious about linking graft atherosclerosis directly to the rejection event. PMID- 1622989 TI - Vascular rejection and its relationship to allograft coronary artery disease. AB - We have prospectively monitored 268 patients by our previously described method of routine immunofluorescence of endomyocardial biopsy specimens. We have classified these patients according to their rejection pattern: cellular, vascular, and mixed. The criteria for these designations have been previously described. In this study we retrospectively reviewed coronary angiograms of these patients to assess the presence and time-course of developing allograft coronary artery disease. All available explanted hearts and postmortem hearts were also assessed by light microscopic examination for acute coronary vasculitis and allograft coronary artery disease and by immunofluorescent microscopy for vascular immune complex deposition in a manner identical to immunofluorescent microscopic examination of endomyocardial biopsy specimens. Patients were also monitored for sensitization to immunoprophylactically administered murine monoclonal CD3 antibody (OKT3) and those demonstrated to be sensitized were separately analyzed. Clinical features and treatment of patients were retrospectively reviewed. We found that 141 patients could be classified as having cellular rejection, 76 as having vascular rejection, and 52 as having a mixed rejection pattern. The allograft survival in vascular rejection patients was significantly worse than in allografts of patients with cellular or mixed rejection, confirming our earlier results. Most importantly, we found a significant difference in the time to the development of allograft coronary artery disease based on the rejection pattern. This difference existed whether or not patients sensitized to OKT3 were excluded from evaluation. Patients with mixed rejection had an intermediate time to the development of allograft coronary artery disease between that of patients with cellular and vascular rejection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1622990 TI - Relation of HLA antibodies and graft atherosclerosis in human cardiac allograft recipients. AB - Although cyclosporine has helped make heart transplantation a clinical reality, long-term survival remains limited by rejection and graft atherosclerosis. We have previously demonstrated the development of alloreactive lymphocytotoxic antibodies in baboon recipients of heterotopic heart transplants despite cyclosporine administration. The hypothesis of the present study is that cyclosporine-treated human heart transplant recipients are also capable of generating strong humoral immune responses that might adversely affect clinical outcome. Serial serum specimens from 240 heart transplant recipients were tested against a reference panel of 70 cells for anti-HLA lymphocytotoxic antibodies. Patients with serum panel reactive antibody levels greater than 10% were considered antibody producers, whereas those with serum panel reactive antibody levels less than 10% were considered nonproducers. To establish the time course of post-transplantation sensitization, we have tested anti-HLA antibodies in sequential sera at 3-month intervals after transplantation. The 4-year actuarial survival rate of those patients whose panel reactive antibody levels were greater than 10% during the first 6 months after transplantation was 70%, whereas the survival rate of patients whose levels were less than 10% during this time was 93%. The results were significantly different (p less than 0.01). Further heterogeneity among the patients was demonstrated by differential analysis of survival in patients who showed (1) panel reactive antibody levels less than 10% in any of the sera obtained during the first year after transplantation, (2) panel reactive antibody levels greater than 10% in sera obtained during the first 6 months but not thereafter, and (3) panel reactive antibody levels greater than 10% throughout the first year after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1622991 TI - Transplant coronary disease: nonimmunologic risk factors. AB - Since the time that coronary artery disease was first described in the transplanted human heart, attempts have been made to define risk factors for its development. Although recent reports have emphasized immunologic and infectious (i.e., cytomegalovirus) mechanisms in the development of transplant coronary disease, the influence of several nonimmunologic risk factors has also been studied. Some of the nonimmunologic risk factors that have been evaluated include recipient characteristics (age, sex, obesity, hyperlipidemia, hypertension, smoking, diabetes mellitus, pretransplantation heart disease), donor characteristics (age, sex), immunosuppressive agents/protocols, and nonimmune mechanisms of endothelial injury (cyclosporine, ischemic time). Studies evaluating the role of these risk factors have produced variable results. One or more studies, however, have suggested an effect of recipient age and sex, donor age and sex, obesity, hyperlipidemia, pretransplantation diagnosis, and ischemic time on the development of transplant coronary disease. The most consistently described relationship has been between hyperlipidemia and transplant coronary disease. Hyperlipidemia is common after heart transplantation, with elevations noted in total cholesterol, low-density lipoprotein cholesterol, and triglycerides. The cause of posttransplantation hyperlipidemia is not well defined, but obesity and the immunosuppressive agents prednisone and cyclosporine play a role. Treatment of posttransplantation hyperlipidemia can be difficult because commonly used lipid-lowering agents have side effects and interactions with immunosuppressive drugs that necessitate caution in their use in the posttransplantation population. Transplant coronary disease almost certainly has a multifactorial cause, with endothelial injury and nonimmunologic risk factors, particularly hyperlipidemia, playing contributory roles. Because hyperlipidemia and the obesity that commonly accompany it are modifiable risk factors, weight loss and treatment of hyperlipidemia are recommended.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1622992 TI - Multicenter evaluation of percutaneous transluminal coronary angioplasty in heart transplant recipients. Cardiac Transplant Angioplasty Study Group. PMID- 1622993 TI - Predictors of survival after repeat heart transplantation. The Registry of the International Society for Heart and Lung Transplantation, and Contributing Investigators. AB - To examine factors potentially predictive of outcome after repeat heart transplantation, data were analyzed for 449 recipients of second allografts reported to the registry of the International Society for Heart and Lung Transplantation and a matched group of 421 primary transplant recipients. Survival was markedly decreased in repeat transplantation patients (1 year actuarial survival rate, 48% vs 79%; p less than 0.001). Univariate analysis showed no impact on survival of recipient age or gender, ischemic time, or transplant center experience. Accelerated coronary artery disease as the cause of allograft failure, longer interval between transplants, lack of preoperative mechanical assistance, and second transplantation after 1985 were predictive of increased survival after repeat transplantation. An "ideal candidate" defined by these predictive variables had a 1-year survival rate of 64%. In addition to the International Society for Heart and Lung Transplantation registry, a multicenter data base was developed with data for 125 repeat transplant recipients and 1325 primary transplant recipients at 13 transplant centers in the United States. In this group of patients the 1-year survival rate was greater than that in the International Society for Heart and Lung Transplantation registry (60% vs 48%), and the impact of the predictive variables listed previously was decreased. The incidence of rejection, infection, and accelerated coronary artery disease was not different between secondary and primary allograft recipients. Nonskin malignancies occurred more frequently in repeat transplantation patients (8% vs 4%; p less than 0.05). Recipients of second allografts were more likely to have major surgical complications, had a higher level of sensitization to HLA antigens, and were more likely to have a positive donor-specific crossmatch (17% vs 2%). A trend toward improved survival was noted in patients with repetition in the second donor of mismatched HLA antigens present in the first donor (1-year survival rate of 68% vs 47%; p = 0.06). We conclude that longer interval between transplants, accelerated coronary artery disease as cause of allograft loss, and lack of preoperative mechanical assistance are predictive of longer survival after repeat transplantation. Nonetheless, the "ideal candidate" for repeat transplantation has an anticipated survival rate significantly less than that expected for primary transplant recipients. PMID- 1622994 TI - Control of intimal hyperplasia by heparin. PMID- 1622995 TI - Preventive treatment of graft coronary vascular disease: the potential role of vasodilator therapy. AB - The prevention or treatment of graft coronary vascular disease is one of the major challenges facing cardiovascular medicine today. Further investigation is necessary to elucidate the mechanisms by which myointimal hyperplasia develops within the coronary vasculature of heart transplants. Studies of several models of the vascular disease, however, suggest that there is an interaction between vasoactive substances, hemodynamic stimuli, and autocrine/paracrine growth factors that governs the vascular remodeling response to vessel injury. In this review I will focus primarily on the role of vasoactive substances and hemodynamic stimuli as determinants of vascular structure. In addition, this review will provide substantiating evidence that advances the postulate that vasodilator therapy may have an adjunctive role in the prevention and treatment of graft coronary vascular disease. It is hoped that this provocative concept will stimulate further investigation of novel therapeutic strategies in the treatment of this disease. PMID- 1622996 TI - Allograft vascular disease: a disease not limited to hearts. PMID- 1622997 TI - Histopathology of graft coronary disease. PMID- 1622998 TI - Cardiac events after heart transplantation: incidence and predictive value of coronary arteriography. AB - Cardiac events from graft arteriopathy, including myocardial infarction, heart failure resulting from previous myocardial infarction, and sudden death, may limit long-term survival after heart transplantation. To determine the incidence of cardiac events and the use of coronary arteriography in predicting these events, the long-term results (mean follow-up, 3.5 years; standard deviation +/- 2.0) of heart transplantation in 427 patients were reviewed. Cardiac events included 19 cases of myocardial infarction, 13 cases of sudden death, and 10 cases of congestive heart failure. All these events occurred after the first year except for three cases of sudden death and one case of myocardial infarction. Cumulative incidence of cardiac events per patient year was 0.9% within the first year, increasing to 1.9% by 5 years. Cardiac events accounted for 3.8% of the deaths by the end of the first year, rising to 18% of total mortality by 7 years after heart transplantation. In patients dying after the first year of transplantation, deaths from sequelae of coronary artery disease occurred in 36% (20/55). The relative risk ("odds ratio") of any cardiac event was 3.44 (p less than 0.05) in patients with angiographic evidence of obstructive disease compared with those without evidence of disease, risk of cardiac death 4.6 (p less than 0.05) and risk of sudden death, 2.4 (not significant). Of the 13 patients who died suddenly, five seen at autopsy were found to have had a recent myocardial infarction. Of all patients who died of heart disease, recent myocardial infarction was detected in nine who were seen at autopsy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1622999 TI - Immunopathology of coronary arteriosclerosis in transplanted hearts. PMID- 1623000 TI - Serial quantitative coronary angiography in the assessment of coronary disease in the transplanted heart. AB - Quantitative angiographic studies with use of cine-videodensitometry after maximal coronary vasodilation with nitroglycerin in 18 "angiographically normal" heart transplant recipients demonstrated significant loss of lumen diameter between years 1 and 3. When sensitive angiographic techniques are used, graft arteriopathy appears to be ubiquitous in heart transplant recipients. PMID- 1623001 TI - Necropsy versus angiography: how accurate is angiography? PMID- 1623002 TI - Intracoronary ultrasound imaging in heart transplant recipients: the Stanford experience. PMID- 1623003 TI - Coronary angiography after heart transplantation: should perioperative study be the "gold standard"? AB - The fact that allograft coronary arteriopathy is frequent and has a poor prognosis means early diagnosis is critical. Furthermore, because of important distinctions between native heart coronary artery disease and allograft arteriopathy, standard noninvasive diagnostic tests seem less sensitive and specific. Assuming that coronary angiography is the optimal method for detection and staging of allograft arteriopathy, one must establish the point at which an initial study should be performed and the incidence of abnormalities in donor hearts. Review of perioperative coronary angiograms in 75 consecutive patients undergoing heart transplantation (within 8 weeks) demonstrated that only six hearts had coronary artery abnormalities: two had focal coronary artery disease, one had an anomalous circumflex coronary artery, and three had nonobstructive calcification of the coronary arteries. To determine if serial quantitative angiography was helpful in detecting progression of coronary disease during a 12 month period, 28 patients underwent baseline and repeat quantification of mean luminal diameter of predetermined segments of the mid and distal portions of the left anterior descending artery. No patient had identifiable disease on the first angiogram, and 12 were studied in the first year of their transplants. During the interval, mean mid left anterior descending coronary diameter was 3.17 +/- 0.6 mm on the first study and 3.06 +/- 0.7 on the second study. Visual assessment of the angiograms, however, identified allograft arteriopathy when two studies were available for inspection in 7 of 28 patients despite no significant diameter reduction of identified coronary segments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623004 TI - Endothelial dysfunction in the development and detection of transplant coronary artery disease. PMID- 1623005 TI - Growth factors and cell proliferation in human transplant arteriosclerosis. PMID- 1623006 TI - The relationship of soluble interleukin-2 receptor levels to allograft arteriopathy after heart transplantation. AB - Certain dynamics of rejection after heart transplantation can be characterized by measuring soluble interleukin-2 receptor levels. To determine whether elevated levels could predict development of coronary artery disease, the mean of three weekly determinations the first month after heart transplantation, as well as values obtained at 6 months, 12 months, 18 months, and 24 months after the procedure, were evaluated. Comparison was made between the groups in whom allograft arteriopathy did or did not develop. Concomitant endomyocardial biopsy scores also were evaluated. Fifty-five patients surviving the initial 30 days after heart transplantation were prospectively followed up. Eighty-five percent were male, and the median age was 51 years. Coronary arteriopathy developed in 15 patients (27%) during a mean follow-up period of 26 months (range, 1 to 54 months). For the early follow-up point, mean (+/- standard deviation) receptor levels for those patients without allograft arteriopathy were 880 +/- 846 U/ml and for those with arteriopathy, 1410 +/- 590 U/ml (p = 0.001). At each follow-up point thereafter, soluble interleukin-2 receptor levels were greater in the group with allograft arteriopathy. Indeed, at all observation points, the group in whom disease developed had levels greater than 1000 U/ml, and these values were, from a statistical standpoint, always greater than the group without detectable arteriopathy. In contradistinction, endomyocardial biopsy scores were no different at either early or late follow-up periods. Allograft arteriopathy after heart transplantation seems predicted by early elevation of plasma soluble interleukin-2 receptor levels, and patients with this difficulty generally have elevated levels during long-term follow-up. PMID- 1623007 TI - Proximal and mid-vessel coronary artery disease in the transplanted heart. PMID- 1623008 TI - Sympathetic reinnervation after heart transplantation in human beings. PMID- 1623009 TI - Cardiac allograft vasculopathy: relationship with acute cellular rejection and histocompatibility. AB - This article reviews the literature and summarizes the data obtained at Loyola University of Chicago about the relationship between rejection, histocompatibility, and cardiac allograft vasculopathy. Both the studies concerning the relationship between rejection and cardiac allograft vasculopathy and those evaluating the impact of histocompatibility on cardiac allograft vasculopathy have produced conflicting results. Most studies are retrospective and include a small number of patients followed up for short periods of time and treated with variable immunosuppressive regimens. In addition, the diagnosis of cardiac allograft vasculopathy is based on angiographic detection of coronary arterial abnormalities, a method that is known to underestimate the presence and severity of cardiac allograft vasculopathy. The ability to assess the impact of histocompatibility on the development of cardiac allograft vasculopathy is also limited by the lack of uniformity in the type and number of HLA variables analyzed, the extreme polymorphism of the HLA antigens and variability in serologic tissue typing techniques and quality. The results of our study suggest that complete mismatch at the HLA-B and -DR loci is associated with higher rejection rates and severity and with increased mortality. We also noted a trend toward a higher incidence of cardiac allograft vasculopathy in patients with complete mismatch at the HLA-DR locus. Future experimental and clinical studies should be done with use of molecular tissue typing techniques to further elucidate the impact of histocompatibility on cardiac allograft vasculopathy. The role of non-HLA antigens in the development of cardiac allograft vasculopathy requires further definition. Because in heart transplantation the short donor ischemic times compatible with a successful outcome limit the feasibility of prospective donor/recipient tissue typing, the development of immunosuppressive drugs that effectively reduce the detrimental effects of tissue incompatibility is crucially needed. PMID- 1623010 TI - Transport of a large neutral amino acid in a human intestinal epithelial cell line (Caco-2): uptake and efflux of phenylalanine. AB - The processes of L-phenylalanine (Phe) uptake and efflux from the apical (AP) and basolateral (BL) sides of an intestinal epithelial cell line (Caco-2) were investigated to further characterize the mechanism of transcellular transport of this amino acid. The results indicated that the initial uptake rates of Phe were saturable with a Km of 2.7 mM for AP uptake and 0.18 mM for BL uptake. Unlike the uptake, the initial efflux rates were shown to be proportional to the intracellular concentrations of Phe. Based on these kinetic studies and determination of other characteristics (e.g., Na+ dependency) of the uptake and efflux processes, it was concluded that AP uptake, BL uptake and BL efflux were distinctly different. This suggests that either different carriers or a different combination of carriers are responsible for the transmembrane transport of this amino acid. When the results of kinetic studies of Phe uptake and efflux were used to determine the rate-limiting step in the AP-to-BL transcellular transport of this amino acid, it was concluded that the BL efflux is the rate-limiting step in the transcellular transport of Phe in the Caco-2 cell monolayers. PMID- 1623011 TI - Effects of culture temperature on the expression of heat-shock proteins in murine ts85 cells. AB - The murine temperature-sensitive cell-cycle mutant, ts85, shows an abnormal induction of heat-shock proteins which is different from the wild type FM3A cells. This paper explores the effect of culture temperature on the expression of heat shock proteins in ts85 cells. When ts85 cells were maintained at 33 or 37 degrees C, these cells synthesized heat-shock protein (hsp) 70 following continuous heating at 39 degrees C or subsequent incubation after heating at 42 degrees C for 15 min. In contrast, these conditions are not conducive for hsp70 synthesis by FM3A cells. Moreover, ts85 cells which were maintained at 37 degrees C synthesized hsp70 following continuous heating at 42 degrees C or subsequent incubation after heating at 45 degrees C for 15 min. The synthesis of hsp70 in these cells corresponded to an increased level of hsp70 mRNA. Furthermore, the constitutive hsp105 level of cells maintained at 33 degrees C was only half of that of cells which were maintained at 37 degrees C, and cells maintained at 33 degrees C were more sensitive to subsequent heat treatment than those maintained at 37 degrees C. These results indicate that culture temperature not only affects the induction of hsp70 mRNA, but also cellular levels of hsp105 and the resulting thermal sensitivity of ts85 cells. These findings suggest that the other phenotypic characteristic of the mutant ts85 cells is also affected by culture temperature. PMID- 1623012 TI - Inhibition of human lymphocyte coproporphyrinogen oxidase activity by metals, bilirubin and haemin. AB - Coproporphyrinogen III oxidase activity in human lymphocytes was found to be inhibited by cadmium and mercury but not by lead. The organo-metal compounds tributyltin and methylmercury were effective inhibitors of this haem biosynthetic pathway enzyme. Haemin (the ultimate product of the pathway) and bilirubin (a product of haem catabolism) were also shown to be inhibitory. Kinetic studies performed under initial velocity conditions showed that bilirubin was a non competitive inhibitor and that one bilirubin molecule was bound to both the enzyme and enzyme substrate complex. The analysis also showed haemin to be a non competitive inhibitor in which two haemin molecules bind to the enzyme whereas the enzyme substrate complex accepts only one haemin molecule. The possible physiological significance of the inhibition of coproporphyrinogen III oxidase activity by haemin and bilirubin is discussed. PMID- 1623013 TI - Opsonophagocytosis of liposomes by peritoneal macrophages and bone marrow reticuloendothelial cells. AB - We investigated the opsonic effect of serum on the phagocytosis of cholesterol poor and cholesterol-rich liposomes with freshly prepared rat bone marrow and peritoneal phagocytes in suspension. The presence of serum in incubation increased the uptake of cholesterol-rich but not cholesterol-poor liposomes in bone marrow cells, whereas serum enhances phagocytosis of both liposome preparations in peritoneal phagocytes. The opsonic activity of serum on the uptake of liposomes by both cell types is destroyed by heat, ammonium hydroxide, and zymosan treatments of serum, which suggests the involvement of complement in phagocytosis of liposomes. However, bone marrow cells and peritoneal macrophages responded differently when incubated with dialysed or EGTA-chelated serum. These treatments result in complete loss of the opsonic effect of serum on the uptake of liposome in bone marrow cells. Addition of serum dialysate or divalent cations to dialysed serum do not reinstall its lost opsonic activity. Thus these results shade doubt on possibility of involvement of complements in phagocytosis of liposomes by bone marrow cells. Dialysed or EGTA-treated serum also failed to promote liposome uptake by peritoneal macrophages but unlike in the case of bone marrow cells replacement of divalent cations to such sera reinstalls its opsonic activity and enhances phagocytosis of liposomes by peritoneal macrophages. These observations suggest the involvement of different serum components on liposome uptake by bone marrow cells and peritoneal macrophages, and emphasize the complexities associated with RES-mediated blood clearance of the intravenously injected liposomes. The properties of these opsonins are compared with those of 'liver-' and 'spleen-specific' opsonins responsible for phagocytosis of liposomes by Kupffer cells and spleen macrophages, respectively [4]. It is suggested that these tissue specific opsonins are responsible for distribution of intravenously injected liposomes in various organs of the reticuloendothelial system. PMID- 1623014 TI - Electron transfer in chromaffin-vesicle ghosts containing peroxidase. AB - In chromaffin vesicles, the enzyme dopamine beta-monooxygenase converts dopamine to norepinephrine. It is believed that reducing equivalents for this reaction are supplied by intravesicular ascorbic acid and that the ascorbate is regenerated by importing electrons from the cytosol with cytochrome b-561 functioning as the transmembrane electron carrier. If this is true, then the ascorbate-regenerating system should be capable of providing reducing equivalents to any ascorbate requiring enzyme, not just dopamine beta-monooxygenase. This may be tested using chromaffin-vesicle ghosts in which an exogenous enzyme, horseradish peroxidase, has been trapped. If ascorbate and peroxidase are trapped together within chromaffin-vesicle ghosts, cytochrome b-561 in the vesicle membrane is found in the reduced form. Subsequent addition of H2O2 causes the cytochrome to become partially oxidized. H2O2 does not cause this oxidation if either peroxidase or ascorbate are absent. This argues that the cytochrome is oxidized by semidehydroascorbate, the oxidation product of ascorbate, rather than by H2O2 or peroxidase directly. The semidehydroascorbate must be internal because the ascorbate from which it is formed is sequestered and inaccessible to external ascorbate oxidase. This shows that cytochrome b-561 can transfer electrons to semidehydroascorbate within the vesicles and that the semidehydroascorbate may be generated by any enzyme, not just dopamine beta-monooxygenase. PMID- 1623015 TI - Recent progress in structure-function and molecular analyses of the pituitary/placental glycoprotein hormone receptors. PMID- 1623016 TI - Effect of insulin-like growth factor-I on the synthesis and distribution of link protein and hyaluronan in explant cultures of articular cartilage. AB - Addition of 20% (v/v) fetal calf serum or insulin-like growth factor-I (IGF-I; 20 ng/ml) to the medium of explant cultures of adult articular cartilage resulted in an increased rate of synthesis of the three components of the proteoglycan aggregate-namely link protein, hyaluronan and aggrecan. Fetal calf serum also stimulated the synthesis of other matrix proteins by articular cartilage compared with tissue maintained in medium alone or medium containing IGF-I. Although addition of fetal calf serum or IGF-I to the culture medium of cartilage explant cultures stimulated both hyaluronan and aggrecan synthesis, no change in the distribution of these two macromolecules between tissue and medium was observed. Approx. 50% of the newly synthesized hyaluronan was retained by the tissue compared to 93% of the labelled aggrecan. Culture conditions had some influence on the distribution of link protein, in cultures maintained in medium alone or in medium containing IGF-I, less than 12% of the newly synthesized link protein was lost to the medium of the cultures. However, in cultures maintained with fetal calf serum between 25% and 19% of the radiolabelled link protein was lost from the matrix of the explants. This work suggests that the chondrocyte synthesizes the macromolecules that make up the proteoglycan aggregate in a co-ordinated manner, thereby retaining the relative amounts of each component of this functionally important complex. PMID- 1623017 TI - Acute and long-term biphasic volume alterations in rat type-II somatotrophs during GH secretory stimulation. AB - The size and shape of growth hormone (GH)-producing rat (type II)-somatotrophs was studied during secretory stimulation by either human GH-releasing hormone (hGHRH(1-29)) or 50 nM extracellular potassium. A new type of perfusion chamber for light microscopy allowed the interpretation of early changes in cell morphology. The exposure to 10 nM hGHRH caused a significant transient decrease in cell volume to 94.4 +/- 2.1% within 2 s. The cell volume recovered to 99.2 +/- 1.3% at 30 s. A second, more gradual volume decrease then followed (60 s), which stabilized at about 92.5 (8 min) and was still present after 20 min of continuous hGHRH exposure. Potassium, 50 mM, gave an immediate and persistent cell volume increase of about 5%. The fluctuation in rat somatotroph volume after hGHRH exposure correlates to a previously observed biphasic GH-secretory pattern involving an initial burst secretion and a second slow phase secretion. The transient early volume decrease may reflect ion fluxes across the membrane and/or the response of the cytoskeleton to calcium mobilization during the GH-secretory onset. The second, persistent, volume decrease closely correlates to the calculated volume of lost GH vesicles. PMID- 1623018 TI - An analysis of rising health care costs. AB - Why are medical costs rising so rapidly? What are the factors involved that influence those costs? Does inflation affect health care costs? Can anything be done? The solutions to these complex issues are not clearly understood. It is clear, however, that the resolutions to these questions must be found quickly. If the causes of rising medical care costs are not promptly diagnosed and treated, we may find our economic health to be in critical condition. This paper attempts to better understand the reasons for increasing health care costs. The role that inflation plays relative to health care costs is investigated. PMID- 1623019 TI - Organization of endoscopic retrograde cholangiopancreatography accessories: designing your own cart. AB - The increasing complexity of endoscopic retrograde cholangiopancreatography procedures has resulted in an ever-widening array of accessories to provide the endoscopist with the necessary equipment to diagnose and treat biliary and pancreatic disorders effectively. The need to organize this volume of accessories efficiently has become a primary concern for gastrointestinal laboratories. GI nurses can work together with physicians to design an organizational system to meet these increasing demands, while at the same time addressing quality assurance and supply inventory. PMID- 1623020 TI - Nutritional assessment in nursing. AB - Patients with gastrointestinal disorders are at high risk for malnutrition. Malnutrition results in an increased length of stay by contributing to the development of complications of disease or surgery. Nurses can help prevent complications by reporting signs and symptoms in hospitalized gastrointestinal patients suffering from malnutrition. Recognition of the methods of nutritional assessment and awareness of the shortcomings of each are needed for accurate assessment of the clinical status. PMID- 1623021 TI - The role of nursing in clinical research trials. AB - The role of nurses and their scope of practice in various clinical settings have become better defined in recent years. Research for most nurses is either new or unfamiliar, despite the fact that research will in some way affect every nurse in clinical practice. The majority of analysis in the literature of nursing research has focused on the relationship between research and clinical practice. What abilities nurses possess and how they can be put into practice for the success of a clinical research trial are the subjects of this article. PMID- 1623022 TI - NuLYTELY (PEG 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution). AB - NuLYTELY (PEG 3350, Sodium Chloride, Sodium Bicarbonate, and Potassium Chloride for Oral Solution), a product from Braintree Laboratories, Inc. is a modification of GoLYTELY (PEG 3350 and Electrolytes for Oral Solution) that has been found to have the same therapeutic advantages in terms of safety, efficacy, speed and patient acceptance. This product was developed to improve upon the taste of GoLYTELY. NuLYTELY represents an effective alternative for bowel cleansing prior to colonoscopy that may be more acceptable to some patients. PMID- 1623023 TI - The role of the pediatric clinical nurse specialist in gastroenterology. AB - Clinical nurse specialists have been employed by hospitals for many years. However, very little published information exists specifically describing the role of the pediatric clinical nurse specialist in the field of gastroenterology. The pediatric GI staff nurse and/or GI assistant may be uncertain as how to best utilize this important nursing resource. The author discusses her own role implementation as a pediatric gastroenterology/nutrition clinical nurse specialist and highlights in particular her role as a resource to the GI nurses. PMID- 1623024 TI - The stomach and effects of surgical alteration. PMID- 1623025 TI - Continuing education for gastroenterology recertification. PMID- 1623026 TI - Primary sclerosing cholangitis: what are the nursing implications? AB - Primary sclerosing cholangitis is characterized by inflammation and fibrotic strictures of the intra- and extrahepatic bile ducts. The diagnosis is confirmed by cholangiography, either endoscopic or percutaneous. An association between primary sclerosing cholangitis and chronic ulcerative colitis has been recognized by physicians for years. To date, there is no known cure for this disease. Several drugs are currently being utilized for symptomatic relief. Therapeutic radiologic and endoscopic procedures are performed to relieve obstruction of the bile ducts and reduce the back pressure on the liver. Surgical procedures are also designed to relieve biliary obstruction and to protect hepatic function. Recently, liver transplantation has become an option for some patients. PMID- 1623027 TI - Odor control in the GI laboratory. PMID- 1623028 TI - Writing for GNJ. PMID- 1623029 TI - Preparatory information and anxiety before sigmoidoscopy: a comparative study. AB - This study compared selected types of information given before sigmoidoscopy to determine if one intervention was superior to the other in decreasing anxiety. The design was two-group, pre- and posttest quasi-experimental. Anxiety was measured by the State-Trait Anxiety Inventory (STAI) and heart rate monitoring. Preparatory information consisted of 3 to 5 min audiotaped messages. Subjects in a convenience sample of 22 men were randomly assigned to one of two information conditions, procedure (control) or procedure plus sensation (experimental). t tests and analysis of variance were used to analyze the data. Data analysis revealed no significant difference (p = .05) in anxiety between groups postintervention. There were no significant changes in heart rate between groups by time or within groups over time. Subjective comments on postsigmoidoscopy questions were strongly positive regarding the benefits of both types of preparatory information. PMID- 1623030 TI - Endoscopy nurses and research. AB - Six staff registered nurses completed research projects related to nursing responsibilities and patient responses in the endoscopy department of an urban hospital. The methodologies, conclusions, and nursing implications of these projects are summarized in this article. PMID- 1623031 TI - Glutaraldehyde: a potential health risk to nurses. AB - This article discusses the potential toxicity of glutaraldehyde, a chemical commonly used in endoscopy units. The literature review cites adverse health effects experienced by workers exposed to glutaraldehyde. The sampling methodology for glutaraldehyde relative to the Occupational Safety and Health standard for glutaraldehyde is presented. Air monitoring should be performed to assess employee exposure to airborne glutaraldehyde in endoscopy departments. Recommendations for reducing exposure to glutaraldehyde in endoscopy units are included. PMID- 1623032 TI - Infectious gastroenteritis in infants and children. AB - Infectious gastroenteritis is a frequent recurring illness in young children. It is caused by a viral agent in 70 to 80% of cases. Bacteria, parasites, and toxins account for the remaining 20 to 30%. A careful history and complete physical examination are the first steps to diagnosing acute gastroenteritis and establishing a treatment plan. The majority of infants and children with infectious gastroenteritis are successfully managed at home. The care of these children focuses on accurately assessing hydration status, maintaining adequate hydration and caloric intake to promote recovery, educating the family about the infection and the treatment plan, and preventing the spread of the infection. PMID- 1623033 TI - Omnipaque (iohexol). AB - The largest nationwide comparative clinical study evaluated 337,647 patients receiving high-osmolar ionic contrast media or low-osmolar nonionic contrast media and the incidence of adverse drug reactions. The overall prevalence of adverse drug reactions was 12.66% in the ionic contrast media group and 3.13% in the nonionic contrast media group. Severe adverse drug reactions occurred in 0.22% of examinations in the ionic contrast media group and in 0.04% of examinations in the nonionic contrast media group. Thus, the use of nonionic contrast medium significantly reduces the frequency of severe and potentially life-threatening adverse drug reactions to contrast media. PMID- 1623034 TI - Listening: what are the listener's responsibilities? PMID- 1623035 TI - Giardiasis. PMID- 1623036 TI - Overtime problems: moving toward better management. PMID- 1623037 TI - Name of organization. PMID- 1623038 TI - Evaluation of teleradiology for interpretation of intravenous urograms. AB - The diagnostic yield of a commercial teleradiology/picture archiving and communication system (ATT-Philips Comm View T/PACS) was evaluated for 100 urograms. A single image from each examination was digitized (2048 x 1684 x 12 bit pixels) and transmitted from a satellite hospital over a T-1 line using the T/PACS system. The video display of each digitized image was reviewed independently by four radiologists. The same four radiologists reviewed the original film images at a different time without knowledge of their T/PACS interpretation. There was no statistically significant difference in the sensitivity for clinical findings between T/PACS (86%) and film (89%). The false positive rate, however, was significantly higher with T/PACS than with film (44 versus 32 false positive findings per 100 films). We conclude that T/PACS of the type studied here demonstrates sufficient sensitivity for the detection of clinically important urographic findings in the emergency setting. A final reading of the original films is still necessary, however, to assure appropriate specificity. PMID- 1623039 TI - Hardware and software requirements for a picture archiving and communication system's diagnostic workstations. AB - Electronic systems (picture archiving and communications systems [PACS]) for image and multimedia data distribution, archiving, and transmission, represent the future of radiology. The workstation is the point of contact between a PACS and the radiologist or referring physician. Therefore, the acceptance of PACS is highly dependent on workstation functionality and performance. This paper, based on our experience in evaluating commercial workstations and on a review of recent literature, describes hardware and software requirements for diagnostic workstations that could be used for making primary diagnoses in a radiology department. Requirements for PACS workstations for use in referring clinics are also briefly described. These workstations must be able to handle the large volume of images to be viewed efficiently, add new functionality to improve the productivity of physicians, technologists, and other health care providers, and provide enough flexibility to allow the electronic systems to grow as medical imaging technology evolves. PMID- 1623041 TI - Automated solid models from serial section images. AB - A new method for creating unambiguous and complete boundary representation solid models with a hybrid polygonal/nonuniform rational B spline representation was developed and tested using computed tomography scans of the wrist. Polygon surface approximation was applied to a sequence of parallel planar outlines of individual bone elements in the wrist. An automated technique for the transformation of edge contours into solid models was implemented. This was performed using a custom batch file command sequence generator coupled to a commercially available mechanical computer-aided design and engineering software system known as I-DEAS (Structural Dynamics Research Corporation, Milford, OH). This transformation software allows the use of biomedical scan slice data with a solid modeler. PMID- 1623040 TI - Clinical impact of picture archiving and communication systems: evaluation of a prototype system. AB - Opinion surveys were gathered before and 6 months after installation of a prototype picture archiving and communication system (PACS) (PACS/1, Siemens Medical Systems, Iselin, NJ). Median turnaround times and the percent of delayed or missing reports were calculated for 1,026 baseline and 8,438 follow-up studies at 6 months. Neuroradiological (neuro) computed tomography (CT) used PACS, while neuro magnetic resonance (MR), body CT, and body MR served as controls. The opinion surveys showed improved service in all categories, including those not directly affected by PACS. PACS images favorably impressed 86% of respondents, but most considered the system too slow, unreliable, and the storage capacity too low. A majority of 81% recommended against purchase of PACS now. There was an overall increase in the median report turnaround time for both neuro CT and the controls. Neuro CT showed a 41% decrease in delayed or missing reports, but controls also showed similar decreases. The effects of this prototype PACS on turnaround time or on report delivery could not be distinguished from section wide changes in CT and MR services. Future improvements in PACS should vigorously address increased speed, reliability, and storage capacity. PMID- 1623042 TI - Chest imaging within the radiology department by means of photostimulable phosphor computed radiography: a review. AB - Photostimulable phosphor computed radiography has been clinically used outside of Japan for more than 8 years. Results of at least 35 quantitative or semiquantitative studies have been published so far in which the clinical utility of computed radiography (CR) is compared with that of conventional screen/film radiography (FR) for the study of the adult chest within the radiology department. The results can be summarized as follows: CR is superior to FR in the mediastinum, retrocardiac region, and subdiaphragmatic recesses, as well as in the evaluation of coronary artery calcifications. CR is reported to be generally superior or equivalent in the detection and evaluation of pulmonary nodules and larger pulmonary opacities. Equivocal results have been reported for pathologies requiring the inspection of fine details, such as interstitial infiltrates or pneumothorax. The studies indicate that image processing algorithms dedicated to the delineation of specific anatomies or pathologies improve clinical performance. PMID- 1623043 TI - Digital imaging in pediatric hospitals. AB - Thirty-nine of 65 children's hospitals in North America responded to a questionnaire regarding their use of digital fluoroscopy and computed radiography (CR) systems. Both digital modalities are very favorably rated by institutions that have them. Budget constraints limit purchases in the other institutions. Picture archiving and communication systems (PACS) networking is not the primary reason for installation of digital systems. Fourteen of 39 hospitals have digital fluoroscopy and another 9 plan installation within 12 months. The three most highly rated benefits of digital fluoroscopy were decreased radiation dose, immediate visualization of the acquired image on the monitor, and the ability to alter image contrast and density. Four of 39 hospitals have computed radiography. The three most highly rated benefits of computed radiography were more stable image quality, ability to alter contrast and density, and PACS networking. PMID- 1623044 TI - A strategy for the progressive introduction of picture archiving and communication systems for a radiology department. AB - An example of strategy for the progressive introduction of picture archiving communication systems (PACS) into a complete global image management system for a Department of Radiology has been developed and quantitatively examined. In general the strategy is based on the earliest reasonable implementation consistent with the evolution of the usage patterns and the state of the technology and its economics. The progressive implementation schedule and the associated numerical estimates of memory requirements in this paper are based on a series of qualitative and quantitative assumptions. The development of the projected strategy and schedule suggests that a time period of 1 1/2 to 2 decades would be required for an aggressive institution to achieve an operational global PACS system. PMID- 1623045 TI - Neural network synthesis of spin echo multiecho sequences. AB - Spin echo multiecho sequences are not frequently used in clinical practice, because they allow the observation of one single slice, imaged at different echo times, for each acquisition. To limit examination time, multislice sequences that include only images derived from one or two echoes are usually acquired. Nevertheless, the strong T2 dependence of multiecho sequences can be used effectively to enhance the contrast between tissues with different T2 and to gather useful diagnostic information. Artificial neural networks can offer new interesting facilities to the radiologist. In fact, the learning capabilities of neural networks allow them to extract the prototypical behavior of a system from a set of examples. After learning, artificial neural networks can emulate the system behavior even in the presence of new inputs, as far as these are not too different from those included in the training set. A conveniently trained neural network can synthesize a multiecho sequence for each slice of a multislice sequence, requiring only two images for each slice to achieve reliable results. When compared with a true multiecho sequence, the images generated by the network preserve the contrast characteristics of the original ones and have a better signal-to-noise (SNR) ratio. In this paper we report the results achieved by using a neural network to reconstruct synthetic spin echo multiecho images of the brain. PMID- 1623046 TI - Tools for medical informatics. AB - Informatics uses words, terms and expressions of various scientific disciplines. The proposed tools, hermeneutics and phenomenology, generate a basis for quality control by establishing the authenticity and validity of such expressions. Without such tools there is the danger that poorly defined expressions obscure true meaning and prevent progress. The method is demonstrated on "objects" as used in "object oriented programming" and on "open systems" as used in the International Standards Organization model for "open system interconnection." PMID- 1623047 TI - [The prevalence of malnutrition in hemodialysis]. AB - Uremic patients undergoing hemodialysis are often catabolic and malnourished. To treat malnutrition effectively, a preliminary nutritional assessment is needed. In a group of 61 chronic uremic patients undergoing maintenance hemodialysis, the authors evaluated the nutritional status with the following indices: 1) assessment of the somatic fat and protein compartments by means of anthropometric measurements (body mass index: BMI, triceps skinfold thickness: TST, and arm muscle circumference: AMC); 2) assessment of the visceral protein compartment (serum albumin); 3) assessment of cell-mediated immunity by means of skin tests and 4) assessment of the dietary intake of nutrients with dietary diaries. BMI and TST were subnormal in 57 and 72% of patients, respectively. CMB and albumin were normal in most. The protein intake was normal, whereas the energy intake tended to be low. Correlations were observed among different anthropomorphic measurements and dietary intake of nutrients. We conclude that there is a tendency to caloric, and in a lower degree protein malnutrition in our patients. PMID- 1623048 TI - [The nutritional status and immunological situation of cancer patients]. AB - A study was performed on the nutritional state of a sample of 138 patients with digestive and extradigestive neoplasias. The study protocol was based on anthropometric, analytical and immunological tests. The main criteria for malnutrition were as follows: loss of 10% or more in normal weight and/or albumen levels of less than 3.5 gr/dl. A global malnutrition percentage of 56.5% was obtained. The highest malnutrition percentages were found among patients with neoplasia of the oesophagus (78.9%) and the lowest in neoplasias of the breast (9.1%). From the nutritional standpoint, neoplasias of the rectum showed an extradigestive behaviour, with a low malnutrition percentage (40%) compared to digestive tumors. The global malnutrition level for the sample studied was 56.6%. The muscular compartment was the most affected in cases of malnutrition. In the PCHR results, no evidence of the effect of the nutritional state on the alteration of these was recorded (Chi 2 = 6.42, p = 0.207). PMID- 1623049 TI - [Parenteral nutrition: a utilization study in a general hospital]. AB - A follow-up of 116 patients initiating parenteral nutrition was performed from December 1990 to March 1991 (average of 18 patients on parenteral nutrition per day, which accounted for a prevalence of 2% compared to total patients admitted), in order to determine a series of characteristics related to the use of parenteral nutrition in our hospital, by means of obtaining concrete, updated information. With regard to the patients, it was observed that 37% of these were suffering from chronic ailments, with more or less incapacitating pathologies. The nutritional state prior to parenteral nutrition was normal in 53% of cases, and the most common reasons for admittance to hospital were neoplasias (27%) and digestive pathology (18%). 42% of the patients were admitted to the ICU and 34% to General Surgery. Indication for parenteral nutrition was intestinal pathology in 23% of cases, followed by pancreatic pathology in 16% of cases and pathology of the oesophagus in 10%; in 45% of cases, it was commenced during the postoperative period. With regard to the composition of the parenteral nutrition, we should mention the use of polyols instead of glucose in 80% of diabetic patients and 75% of patients with pancreatitis, the widespread use of mixture of 50% medium and long chain triglycerides and the use of amino acid solutions with 20% branched chain in most patients, both in situations of stress and maintenance. PMID- 1623050 TI - [The consumption of commercial foods in childhood. The influence of a nutritional information program]. AB - In order to perform an in-depth study on food standards among school children and evaluate the effect of a nutritional educational programme on eating habits, an analysis was made of the data on the intake of foods over a period of 1,890 days, in 187 school children from 2 schools in the Leganes-Fuenlabrada area. The consumption of global and stratified rations was quantified based on age, commercial foods (buns, fried foods and sweets) accounting for a large part of the children's diet, as well as dairy products, vegetables, fruit and fish, representing basic foodstuffs supposed to form part of their diet. The consumption of these was compared in two stages, before and after receiving the educational programme. It was observed that there was an excessive consumption of foodstuffs considered as lacking in nutritional value (commercial), which increased with age and a lack of natural foods evaluated in their food standards. We also observed that the applied health intervention modified the consumption of these foods recently incorporated into the children's diet, without achieving results with regard to family eating habits. PMID- 1623051 TI - [The development of an informational logic support for aiding diagnosis and treatment. The Edecan-Med program. I. The assessment of nutritional status]. AB - We present the elaboration of an informatic program (Informatic Logic Support [SLI]) as a clinical help in diagnosis and treatment, for use by compatible computers PC. In this first part dedicated to artificial nutrition, we explain the scientific support, the capture of anthropometric and biochemical data, the processing, the results and the conclusions delivered by the computer that inform us about all the calculated nutritional parameters the type of malnutrition, the surgical risk of morbimortality (nutritional prognostic), and the caloric needs. PMID- 1623052 TI - [A comparative study of 5 infusion pumps: an evaluation of their suitability for administering parenteral nutrition]. AB - To facilitate the control of administering parenteral nutrition (PN), the tendency is to replace traditional infusion equipment with infusion pumps. The aim of this study is to determine the characteristics that a pump should have for infusing PN mixtures and, based on these, to evaluate five models available on the market. The pumps evaluated, all with volumetric programming were: Becton Dickinson VIP II (Prim); Life-Care Pump Model 4 (Abbot-Shaw); Infusomat Secura 1.000 (Braun); Flo-gard (tm) 6,200 (Baxter) and IVAC-591 (Ivac). The following method was used: a) Definition of 16 basic requisites and 7 secondary requisites considered necessary in a PN pump, in accordance with the following criteria: safety, practical usage, comfort and hospital circuits. b) Review and checking of the technical reports on each pump. c) Laboratory tests simulating PN infusion, evaluating the regularity and precision of the infusion speed, and d) Subjective evaluation survey. All the pumps under study complied with the basic requisites. There were differences in the subjective evaluation, although with regard to all concepts and models a score of over 2.5 was reached in a scale of 0 to 5. The highest and lowest values with regard to regularity and precision were within the following ranges: +/- 0.6 ml/h(-)+/- 0.0 ml/h and + 3.4%(-)-1.6% respectively, and no instance of values outside the established ones was detected. The pumps only partly complied with the secondary requisites. Finally, the criteria for defining the most significant requisites was reviewed, based on the services offered by the existing pumps, as well as techniques for determining regularity and precision.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623053 TI - [The effect of the customary intake of energy and nutrients on the nutritional status of schoolchildren 6 to 15 years old]. AB - An investigation was performed with regard to the effect of consuming energy and energetic nutrients, cholesterol and fibre in 187 children aged from 6 to 15 years in the Leganes-Fuenlabrada Health Area (Madrid) on the build and nutritional state of the children. An excessive global intake of calories, total and saturated fats, cholesterol and proteins was observed, and a deficit of carbohydrates, with a corresponding loss of nutritional balance. It should be mentioned that 74% of the children studied could be considered normal from the nutritional standpoint, with 18% of overweight children and 8% of children suffering from malnutrition. The results also provided information on the effect of the consumption of energy and fats on the weight and obesity of the children, as well as the interesting relationship between the habitual intake of proteins and carbohydrates on the children's build. PMID- 1623054 TI - A long-term clinical trial of interferon alpha-therapy in essential thrombocythemia. AB - In a prospective clinical trial involving six patients suffering from essential thrombocythemia (ET), recombinant human interferon alpha 2b significantly and consistently lowered highly elevated peripheral platelet numbers over long time periods. One patient has now been on continuous treatment for 4 years. During the treatment phase none of the patients suffered from bleeding episodes, thrombosis or disturbances of the microcirculation. The interferon maintenance dose varies considerably from patient to patient, but it is usually much lower than the induction dose. One of the patients had to be withdrawn from the study due to interferon-specific chronic toxicity concomitant with the development of non neutralizing interferon antibodies. With the exception of one patient, stopping interferon treatment led to an increase in peripheral platelet numbers of up to one million cells per microliter of blood within 4 to 12 weeks. We conclude that interferon alpha can correct peripheral thrombocytosis in selected patients with essential thrombocythemia over a period of years and prevent morbidity attributable to this disease. PMID- 1623055 TI - Differences of cellular composition and adhesion molecule expression in "leukemic" as compared with "normal" human long-term bone marrow cultures. AB - Human long-term bone marrow cultures (HLTBMCs) were established with bone marrow samples collected from 15 patients with acute myeloid leukemia (AML) and compared with HLTBMCs from eight healthy volunteers. During 6 weeks of culture, the cellular composition of HLTBMCs was quantitatively studied. The cells of the HLTBMCs were divided into three main categories: fibroblasts, macrophages, and 'other cells' (endothelial cells, hematopoietic cells and undefined cells). HLTBMCs derived from healthy volunteers demonstrated a very consistent development. The number of fibroblasts increased during culture and the number of macrophages decreased, resulting in a steady state after 3 weeks of culture. In contrast, HLTBMCs derived from patients with AML showed a strikingly different pattern of irregular development and a steady state was not reached under our conditions. The APAAP technique was used to demonstrate expression of adhesion molecules. VLA2, VLA5, VLA6, LFA1, Mac1, p150/95, beta 2-chain, HCAM, ICAM1, NCAM, and VCAM1 were more expressed on 'normal' as compared with 'leukemic' bone marrow stromal cells, although this reached significance only for beta 2-chain and NCAM. VLA1, 3, and 4 were expressed in a higher percentage on 'leukemic' stroma (not significant). More expression was seen on 'normal' as opposed to 'leukemic' macrophages for the adhesion molecules tested, except for VLA5. The differences reached significance for the majority of molecules tested. It is concluded that striking differences exist in cellular composition and adhesion molecule expression between HLTBMCs from healthy individuals and those from patients with AML. This may have an impact on the pathogenesis of AML. PMID- 1623056 TI - Effect of cimetidine on burst-promoting activity of normal T lymphocytes. AB - The effect of cimetidine, an inhibitor of suppressor T lymphocytes, on the burst promoting activity (BPA) of normal T lymphocytes has been studied. Cimetidine has been shown to increase the BPA of normal T lymphocytes, both when added to the culture and when T lymphocytes were preincubated for 1 h with it. Cimetidine had no direct effect on the in vitro growth of burst-forming units (BFU-E). Our results show that CD8 suppressor T lymphocytes inhibit the in vitro growth of BFU E in normal conditions, either directly or through inhibition of BPA of CD4 helper T lymphocytes. Cimetidine has proved to be a useful tool for investigating the hematological role of T-lymphocyte subsets in normal and pathological conditions. PMID- 1623057 TI - Improved microbioassay for plasma erythropoietin based on CFU-E colony formation. AB - We examined the conditions necessary for performing a reliable erythropoietin (EPO) assay based on CFU-E colony formation in fetal mouse liver cell (FMLC) microcultures using 96-well microtiter plates. Both linearity of colony numbers with the number of cells plated and comparison among the colony ratios at various densities of seeding cells indicated that the colonies originated from a single progenitor cell when 7500 or fewer cells were plated into individual microtiter wells. About a twofold CFU-E enrichment in 12- to 13-day FMLC was achieved by Ficoll-Paque centrifugation. Plasma treated with acid-boiling stimulated the colony formation most and contained no colony inhibitor. Dose-response curve for the plasma was parallel to the EPO standard curve. The "erythroid colony stimulating activity" in the plasma was additive to that in the standard EPO, and was completely neutralized by a monoclonal antibody against recombinant human EPO. Using the assay procedure thus established, plasma EPO titer was determined in normal subjects, in patients with nonuremic anemia and polycythemia vera, and in dialysis patients with chronic renal failure. The use of different preparations of standard EPO resulted in a significant difference in the titers because their dose-response curves differed from one another. An inverse relationship was found between EPO titers and hemoglobin concentrations in the nonuremic anemic patients, but not in the dialysis patients with about one half the normal EPO level. PMID- 1623059 TI - Chronic systemic candidiasis in acute leukemia. AB - In the past few years a new syndrome of invasive Candida infection, the so-called hepatosplenic or chronic systemic candidiasis (CSC), has been recognized with increasing frequency in neutropenic patients. From January 1985 to December 1990, ten of 305 acute leukemia (AL) patients treated at our institution were diagnosed as having CSC. In contrast, during the same period this type of Candida infection was not observed in any patient with hematological diseases other than AL treated in our center, including 277 patients who underwent bone marrow transplantation. All patients with CSC had fever and hepatomegaly, and five complained of abdominal pain. Seven patients had neutrophilic leukocytosis and six an increased serum alkaline phosphatase activity. Abdominal computed tomography and ultrasound study showed typical lesions in eight and seven patients, respectively. In four patients a laparoscopy-guided needle liver biopsy displayed yellowish nodules on the liver surface, and the histologic study revealed large granulomas with yeasts and pseudohyphae. All patients were given amphotericin B (mean: 4.6 g, range: 1 12.5 g) and 5-fluorocytosine, and five received fluconazole. No patient died as a direct consequence of CSC and in six the infection resolved. Finally, once controlled, the infectious complication did not preclude subsequent intensive antileukemic therapy, including bone marrow transplantation. PMID- 1623058 TI - The growth capacity of hematopoietic progenitor cells in severe neutropenia induced by famotidine. AB - In four cases of severe neutropenia of unknown origin we found a strong inhibition of the growth of granulocyte-macrophage (GM) progenitor cells. The development of GM colonies in culture (GM-CFU-c) was more than 80% reduced in comparison to the control group. In particular, the interleukin 3-(IL-3) and granulocyte macrophage colony-stimulating factor-(GM-CSF) dependent growth was affected; a combination of growth factors (IL-3, GM-CSF, and G-CSF, the granulocyte colony-stimulating factor) resulted in a less reduced growth. The findings were primarily compatible with drug-induced bone marrow failure. Among the medications given to the patients, famotidine, an H2-receptor blocker, was discussed as an agent which possibly triggers off this process. After the withdrawal of famotidine, in three cases a continual increase of the growth of GM precursors was detected, reaching the normal level 7-17 days later. In one case, further investigations of the progenitor cells could not be carried out due to the death of the patient, but the rapid increase of neutrophils in the peripheral blood after withdrawal of famotidine pointed to the recovery of hematopoiesis. In vitro studies showed that famotidine, depending on the dose, inhibits the single growth factor-dependent colony growth (IL-3, GM-CSF, or G-CSF) of bone marrow progenitors from a concentration as low as 10 micrograms/ml. With the combination of all three growth factors only slight inhibitory effects were detectable (up to 150 micrograms/ml famotidine). These results indicate that famotidine, in common with other H2-receptor antagonists, can affect hematopoietic progenitor cells. However, the plasma concentration of famotidine normally used in ulcer therapy does not seem to influence the hematopoiesis. Apparently, the progenitor cells of only a few patients possess a higher sensitivity to the blockade of H2-receptors at this concentration of famotidine. This was demonstrated in one case (patient 3) 2 years after the patient had recovered from famotidine-induced neutropenia. The growth of peripheral myeloid, erythroid, and multilineage progenitor cells of this patient was remarkably reduced even at famotidine concentrations of 0.1-5.0 micron/ml whereas in the control group no inhibition was detected at these famotidine concentrations. Again, the IL-3-dependent colony formation was more affected than in the case of the combination of IL-3, GM-CSF, and G-CSF. After the removal of accessory cells the inhibitory effect of famotidine persisted, demonstrating that accessory cells do not play a major role in this process. PMID- 1623060 TI - Thrombotic thrombocytopenic purpura in early pregnancy with maternal and fetal survival. AB - Thrombotic thrombocytopenic purpura (TTP) is a hematologic disorder which is clinically characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurologic symptoms, and cardiac and renal involvement. The pathogenic mechanisms of this disease are poorly understood. It is well known that TTP is associated with pregnancy and that prognosis for the mother and child is poor. We present the first case of a severe TTP diagnosed in the first trimester of pregnancy (13th week of gestation) with maternal survival and birth of a healthy child which required continuous and intensive treatment with plasma therapy until delivery. During a period of 24 weeks several attempts to discontinue plasma therapy failed because of continuous active disease, and it became evident that plasma infusions were not as effective as plasma exchanges. The fact that the patient entered into remission soon after delivery of a healthy child by cesarean section in the 37th gestational week shows that in this case pregnancy activated an unknown factor which does not cross the placenta and which can be removed by plasmapheresis. PMID- 1623061 TI - Use of a synthetic protease inhibitor for the treatment of L-asparaginase-induced acute pancreatitis complicated by disseminated intravascular coagulation. AB - In two patients receiving L-asparaginase therapy, severe acute pancreatitis complicated by disseminated intravascular coagulation (DIC) developed. In both cases it was successfully treated with continuous infusion of a synthetic protease inhibitor, nafamostat mesilate. In this report, we briefly discuss the clinical efficacy of the synthetic protease inhibitor in treating such cases. PMID- 1623062 TI - Career alternatives. The role of the case manager. PMID- 1623063 TI - Make competition your friend. PMID- 1623064 TI - Timeline helps put case in perspective. PMID- 1623065 TI - Admissibility of expert evidence in toxic tort cases. PMID- 1623066 TI - CPITN application in regular dental practice. AB - The periodontal status of 8862 dentulous and partially dentulous inhabitants of the Federal Republic of Germany was investigated in various dental practices, using the CPITN, developed by the World Health Organization. The results show that a total of only 4.3% of those examined have a healthy periodontal apparatus and thus require no periodontal treatment. At least detailed oral hygiene instruction needs to be given to 95.7% of all subjects. Furthermore, 80% patients with periodontal disease require scaling or root planing, and 10% of them require periodontal surgery. The treatment of shallow gingival pocketing (CPITN 3) is predominant in every age group, and every fifth patient aged 35 years or more is need of periodontal surgery. This high frequency rate of periodontal disease illustrates the urgent necessity in regular dental practice for each and every patient to undergo periodontal screening. Such screening, based on the time saving CPITN, is to be recommended as it ensures fast, reliable determination of the periodontal status of each individual patient and the treatment needs involved. PMID- 1623067 TI - [The stereognathograph PC--test results with the new version of the device]. AB - The PC stereognathograph was investigated for measurement errors in laboratory experiments on an optical bench as well as on an articulator. The values obtained were compared with the data of the predecessor model. A substantial reduction in the linearity in transverse measurements has been effected, so that these are now within acceptable limits. A variation of linearity factors which can be avoided by electronic fine adjustment still arises owing to incongruence of the six measurement channels. The hinge axis can be localized very well on the articulator. By and large, the announced correction of the projection error which we have demanded has not been implemented up to now. In view of the clear imaging of condylar movement in space and time on the monitor and the adequate precision of the clinical measurements effected, the PC stereognathograph appears to be a valuable system for instrumental diagnostics. PMID- 1623068 TI - [The experiences of 10 years of an interdisciplinary dysgnathia consultation]. AB - We regard the down-fracture technique in maxillary osteotomy of the Le Fort-I plane, the possibility of simultaneous bimaxillary procedure as well as adaptation osteotomy in the maxillary region, semirigid osteosynthesis technique with miniplates and miniscrews and consistent interdisciplinary cooperation in planning and therapy as the most important advances during the last ten years. A joint dysgnathia clinic has proved to be of great benefit. Sagittal and vertical recurrences are avoided in particular using the bimaxillary procedure and a timely and consistent orthodontic follow-up treatment. The quality of the definitive result crucially depends on the consistency and quality of the immediate postoperative orthodontic follow-up treatment. PMID- 1623070 TI - [The therapy and prognosis of birth-injury-related joint dislocations and fractures]. PMID- 1623069 TI - [Histological study of the resorbed dental crowns of impacted wisdom teeth]. AB - Undecalcified sections of 31 impacted third molars are examined histologically for signs of resorption. Resorption starts at small spots in enamel, progresses to dentin and may even penetrate the pulp cavity. The incidence of such resorption processes increases after the age fifty. A prerequisite for resorption is the loss of reduced ameloblastic epithelium. Histological examination reveals multinuclear giant cells and apposition of spongious bone to destroyed dental substances. The results is dental ankylosis. Because partially resorbed teeth or ankylosed teeth may lead to serious surgical difficulties, impacted wisdom teeth without any clinical symptoms and without pathologic radiological findings should always be extracted at a young age. PMID- 1623071 TI - [Individual plaque flora determination in periodontal diseases. Methods and standardization]. AB - The dental plaque of 15 patients with gingivitis and of 15 patients with marginal periodontitis was won by means of two different methods of isolation and sampling. Either the plaque was sampled by a scaler with and without covering the crown. The estimation of plaque-microflora was done by microscopical and cultural bacteriological methods. Differences in the composition of plaque-microflora could be found in dependence of method used in isolation and sampling. Also differences in bacterial colonisation of different regions were found using the same technique of sampling. The subgingival plaque in marginal periodontitis was different of the plaque in gingivitis. In plaque-microflora of periodontitis the percentage of gram-positive cocci and rods was decreasing, the percentage of gram negative and mobile bacteria was increasing compared with the bacterial flora in gingivitis. In the subgingival plaque in gingivitis streptococci and actinomyces were the predominant bacteria. PMID- 1623072 TI - Emergence of Enterococcus as a significant pathogen. PMID- 1623074 TI - The disappearance of multiresistant Staphylococcus aureus in Denmark: changes in strains of the 83A complex between 1969 and 1989. AB - During the 1960s multiresistant strains of Staphylococcus aureus were problematic in Denmark and other countries. An analysis of the phage types and antibiotic resistance patterns of S. aureus strains collected from approximately 20,000 Danish patients per year has given us a general picture of the evolution of S. aureus in Denmark during the last 30 years. Multiresistant S. aureus (i.e., strains resistant to penicillin, streptomycin, and tetracycline and often to methicillin and erythromycin as well) belonged mostly to the 83A complex, a relatively homogeneous subset of group III strains that can be further divided into six subtypes. The disappearance of multiresistant strains in Denmark began with a decline in the frequency of isolation of the most resistant subtypes, which was followed by a gradual decrease in the resistance of all 83A subtypes; thus strains of the 83A complex ultimately became no more resistant than other strains. As the proportion of strains of S. aureus accounted for by the 83A complex declined from 24% in 1969 to 6% by the late 1980s, this complex was replaced by strains of type 95, the 94,96 complex, and group II, all of which only rarely show resistance to multiple agents. PMID- 1623073 TI - Management of occupational exposures to bloodborne pathogens: hepatitis B virus, hepatitis C virus, and human immunodeficiency virus. AB - Being a health care worker in today's world is not without risks. Accidental exposure to blood carries with it a definite risk of transmission of infection by various bloodborne pathogens, especially the hepatitis B, hepatitis C, and human immunodeficiency viruses. While infectious disease specialists, hospital epidemiologists, and infection control clinicians can develop many important strategies to reduce this risk--aggressive training, utilization of safer needles, identification of high-risk activities, and efficient disposal systems- their overriding responsibility is to design and implement a comprehensive plan for expeditiously and effectively dealing with accidental exposures when they occur. Among other things, the plan must address a number of key issues, including testing, administering postexposure prophylaxis, providing short- and long-term follow-up care, and, particularly, counseling for helping the health care worker deal with the tremendous anxiety associated with the injury. Drs. Julie L. Gerberding of the University of California, San Francisco, and San Francisco General Hospital and David K. Henderson of the National Institutes of Health and the Warren G. Magnuson Clinical Center have both made significant contributions in this area; in this month's AIDS Commentary they discuss the essential elements of such a plan. PMID- 1623075 TI - Varied presentations and responses to treatment of infections caused by Mycobacterium haemophilum in patients with AIDS. AB - We describe three patients with AIDS who developed clinically significant infection with Mycobacterium haemophilum. One patient had skin and bone involvement and suspected laryngeal involvement; the second had extensive abdominal adenopathy with partial bowel obstruction; and the third presented with limited skin involvement. Each patient responded transiently to antimycobacterial therapy, but disease recurred and progressed in all three cases. Recovery of M. haemophilum requires a high level of clinical suspicion and special handling of mycobacterial cultures by the microbiology laboratory, including cultivation on enriched chocolate agar or heme-supplemented media and incubation at 30 degrees C for up to 8 weeks. Characteristic patterns of drug susceptibility for this organism have been only partially defined. Reported responses to antimycobacterial therapy in AIDS patients with M. haemophilum infection have been poor, and the optimal therapeutic regimen is not yet known. The prognosis for recovery appears to depend heavily on host-related factors, particularly the degree of immunosuppression. PMID- 1623076 TI - Septicemia and shock syndrome due to viridans streptococci: a case-control study of predisposing factors. AB - Between 1972 and 1989, the incidence of viridans streptococcal bacteremia at the University of Texas M. D. Anderson Cancer Center in Houston increased from one case per 10,000 admissions to 47 cases per 10,000 admissions (P less than .0001). A shock syndrome characterized by hypotension, rash, palmar desquamation, adult respiratory distress syndrome, and occasionally death developed in 26% of cases of streptococcal septicemia but in only 4% of cases of septicemia involving other gram-positive bacteria (P = .0005). The risk of streptococcal infection increased with the prophylactic administration of trimethoprim-sulfamethoxazole or a fluoroquinolone (P less than .0001) and with profound neutropenia (P less than .0001). Treatment of chemotherapy-induced gastritis with antacids or with histamine type 2 (H2) antagonists was associated with a sevenfold increase in risk (P less than .001), while sucralfate therapy did not increase risk (P = .65). Streptococcal infection may result from gastric overgrowth of organisms resistant to trimethoprim-sulfamethoxazole in an antacid- or H2 antagonist induced alkaline environment, with the gastrointestinal tract ulceration caused by antineoplastic therapy providing a convenient portal of entry. In patients receiving chemotherapy, replacement of antacids or H2 antagonists by an acid sparing regimen should be considered to preserve the natural acidic barrier to infection. PMID- 1623077 TI - Infection caused by Mycobacterium chelonae: a diagnostic and therapeutic problem in the neutropenic patient. AB - Mycobacterium chelonae, a rapidly growing species, is a significant cause of fever in neutropenic patients. We describe three febrile neutropenic patients at the Royal Free Hospital from whom this organism was isolated on several occasions. The condition of the first patient improved as the neutrophil count recovered. The second patient developed pulmonary disease and required surgical resection of a pulmonary lesion. The third patient, who had rapidly progressive, diffuse pulmonary disease, responded to an antibiotic regimen including erythromycin and ciprofloxacin. Both our findings and reports in the literature suggest that neutropenia may be a major risk factor for disseminated infection due to M. chelonae and that treatment is effective only after the recovery of the neutrophil count. PMID- 1623078 TI - Gram-negative sepsis and the adult respiratory distress syndrome. AB - Gram-negative sepsis has dramatically increased in frequency throughout the twentieth century in the United States. Currently, approximately 200,000 patients develop gram-negative sepsis each year in this country. Of these, about one quarter develop the adult respiratory distress syndrome (ARDS). Among these critically ill patients, mortality is estimated at 60%-90%. In the complex series of events leading to acute lung injury in gram-negative sepsis, endotoxin is the proximal mediator. Although endotoxin may be capable of causing direct injury to the pulmonary endothelium, its primary role is as a trigger activating inflammatory agents, including complement, neutrophils, and platelets, and inducing the production of cytokines and arachidonic acid metabolites. The end results are impairment of the endothelial barrier, diffusely increased capillary permeability, and adherence of neutrophils to the endothelium with subsequent migration into the tissues. The consequent clinical syndrome is one of acute respiratory distress with pulmonary edema, poorly compliant lungs, and refractory hypoxemia. Endothelial injury often becomes widespread, leading to the failure of multiple organs, including the kidneys, brain, intestine, and liver. Conventional therapy consists of supplemental oxygen, positive end-expiratory pressure, inotropic agents, fluid management, and antibiotics aimed at the offending pathogen. Recent discoveries regarding the mediators of sepsis as well as the expansion of the biotechnological armamentarium have provided clinicians with a plethora of new tools with which to manipulate the host's inflammatory response. The challenge for the next decade will be to ensure the safety, efficacy, and cost-effective use of these expensive but potentially lifesaving immunomodulators, singly or in combination, as adjuvant therapy. PMID- 1623079 TI - Disseminated infection with Mycobacterium gordonae: report of a case and critical review of the literature. AB - Mycobacterium gordonae is only rarely a cause of infection despite its ubiquity in the environment. We describe an 11-year-old girl with disseminated infection due to M. gordonae whose course was complicated by renal failure requiring hemodialysis but who recovered after 15 months of chemotherapy. In a literature search we identified 23 additional cases of infection attributed to M. gordonae, with involvement of the lungs (eight), soft tissue (seven), the peritoneal cavity (three), the cornea (one), and with disseminated disease (five patients, including ours). Two patients were infected with human immunodeficiency virus. We assessed the patterns of infection characteristic of each site and the antibiotic sensitivities of the isolates. Adequate documentation of M. gordonae infection (e.g., amount of growth per culture, detection of specific biochemical characteristics, and confirmation of the organism's identity by a reference center) was lacking in many reports. M. gordonae should not automatically be dismissed as a contaminant when isolated from clinical material. Additional studies are required to establish the extent of this organism's pathogenic role. PMID- 1623080 TI - Infection with Borna disease virus: molecular and immunobiological characterization of the agent. AB - Borna disease virus (BDV), which seems to be distinct from all other known viruses, exhibits a unique mechanism of pathogenesis. This review highlights several aspects of the biology of infection with this virus and summarizes the preliminary characterization of the agent. Studies on BDV may help to illuminate several important areas of neurobiology, including the mechanisms regulating the replication of a new type of RNA virus in the nuclei of neural cells, the neuroinvasiveness and neurotropism of such viruses, their T cell-mediated immunopathology, tolerance in newborn animals to persistent viral infection of the central nervous system, and behavioral diseases and eating disorders induced by such agents. PMID- 1623081 TI - Antimicrobial treatment of orthopedic implant-related infections with rifampin combinations. AB - The purpose of this prospective clinical study is to evaluate the role of combination chemotherapy with rifampin in the treatment of orthopedic device related infections in which the implant could not be removed. Eleven patients with orthopedic implant-related infections due to staphylococci or streptococci were treated with the implant in situ. Each antimicrobial regimen included rifampin in combination with a beta-lactam antibiotic or ciprofloxacin. The median duration of treatment with rifampin was 86 days (range, 15-336 days) with a median follow-up of greater than 24 months after cessation of therapy. Treatment was successful for 82% of patients. Failures were associated with documented inappropriate treatment. These preliminary clinical data are supported by data from in vitro studies and animal experiments. Combination therapy with rifampin, in particular rifampin and a quinolone, should be considered for patients with orthopedic implant-related infections if the implant cannot be removed. PMID- 1623082 TI - Fever in a couple vacationing in the mountains of southern California. PMID- 1623083 TI - Optimal duration of therapy for catheter-related Staphylococcus aureus bacteremia. PMID- 1623084 TI - Meningitis caused by group B streptococcus in association with cerebrospinal rhinorrhea. PMID- 1623085 TI - Immunity to measles during pregnancy. PMID- 1623086 TI - Mixed bacterial meningitis associated with CSF leak. PMID- 1623087 TI - Infections due to Stomatococcus mucilaginosus: report of two new cases and review. PMID- 1623088 TI - Splenic tuberculous abscess in patients positive for human immunodeficiency virus: report of two cases and review. PMID- 1623089 TI - Pasteurella multocida infection after a Tasmanian devil bite. PMID- 1623090 TI - Response to treatment of infection due to Mycobacterium avium complex with trimethoprim-sulfamethoxazole. PMID- 1623091 TI - Exchange transfusion as an adjunct to the treatment of severe falciparum malaria. PMID- 1623092 TI - Herpes zoster-induced acute hyperparathyroid crisis. PMID- 1623093 TI - Acute bacterial gastroenteritis caused by Hafnia alvei. PMID- 1623094 TI - [Reactive thrombocytosis verses primary thrombocythemia]. PMID- 1623095 TI - [Clinical-endoscopic-histological correlations in gastric pathology. I]. AB - We have conducted a blind cross-selectional study with 150 consecutive patients undergoing fibrogastroscopy and biopsy of the antral mucosa. The endoscopic sensitivity for the diagnosis of the several types of gastritis, is low (63%), although this technique is highly sensitive for other types of pathology. Consequently, we conclude that, in all endoscopic explorations, at least one biopsy of the antral mucosa must be done, given the anatomopathological definition of gastritis. In addition, the clinical use of this term should be restricted to the histologically demonstrated cases. PMID- 1623096 TI - [Effectiveness of the concentrator as a supply source in home oxygen therapy]. AB - The oxygen concentrator is an effective supply source in home oxygen-therapy (HO). In order to study the effectivity of the concentrator in HO, we visited at home 31 patients using the concentrator as the only oxygen supply source in the exit gas and counted the hours of concentrator usage. Only 13 concentrators (41.9%) supplied a percentage of oxygen higher than 87% at a flow of two liters per minute. In three cases (9.7%), sporadic control measures of the percentage of oxygen in the exit gas were being taken and only four patients (12.9%) said that these controls were made monthly. The concentrator did not supply the adequate percentage of oxygen in 12 out of the 29 patients correctly taking the HO, so the effectivity of the treatment can only be expected in 28.6% of studied cases. The concentrator operates well under ideal conditions, but potential breakdowns in standard conditions of use must be considered. The efficiency of the HO with concentrator in our environment is very low, but it can be improved with regular controls of the concentrators or the introduction of devices warning the patient when they detect a reduction of the percentage of oxygen in the exit gas. PMID- 1623097 TI - [What is the normal threshold of glycemia in our elderly?]. AB - The aim of this paper is to study the evolution of basal glucemia and TTOG with age, as well as the prevalence of diabetes in different age groups. A cross sectional descriptive study was designed, with a polystratified random sampling method among the whole adult population of Leon. In addition to fill in a questionnaire, basal glucemia was measured with a capillary reflectometer and a TTOG with 75 g. The effect of age on the average values of basal glucemia and on TTOG glucemia was no demonstrated. A significant correlation between the prevalence of the disease and the age of subjects was also observed, being maximum in the age group 60-69 (14.50%). After discussing the results, we conclude that only prospective studies will be able to establish the threshold of glucose tolerance-intolerance, beyond which the risk increases. PMID- 1623098 TI - [Lung cancer in Internal Medicine]. AB - In order to study the several forms of presentation of lung cancer in our environment, we have analyzed characteristics, age, tobacco consumption, stage of onset and location of initial metastasis in 20 patients in whom the diagnosis of this neoplasia had been established. The still low incidence of lung cancer among the female population is the more significant feature of our group of patients, compared with other series from Anglo-Saxon countries. PMID- 1623099 TI - [Intraparenchymal cerebral hemorrhage and cocaine]. AB - Medical problems related to cocaine consumption are not rare in our environment; however, to this respect, descriptions in the spanish literature are scarce. We present three cases of intracerebral hemorrhage which occurred after cocaine consumption (intranasal route in two cases and intravenous route in one case). In the three cases, another associated risk factor was observed (alcohol in one case, hypertension in other case, arteriovenous malformation in the third case). We comment on the pathophysiological theories of the cause of bleeding, high lighting the routine search of this association. PMID- 1623100 TI - [Ehlers-Danlos's syndrome type II. A family study]. AB - We describe the presence of EDS type II in a family whose diagnosis was lately established by medical consultation of one of its members suffering from hyperuricemia and gout. We stress the relevance of an early diagnosis of this syndrome as a means to prevent and reduce as much as possible cardiovascular, hemorrhagic and surgical systemic complications associated to this disease. PMID- 1623101 TI - [Osteoporosis as the first manifestation of minor beta-thalassemia]. AB - We present the case of a 48-year-old premenopausal woman with right lumbosciatalgia secondary to osteoporosic vertebral collapses. Two of her three offsprings, a 31-year-old man and a 16-year-old woman, had chronic dorsolumbalgia, the study of which suggested the diagnosis of minor beta thalassemia. As opposed to thalassemic osteoarthropathy, frequently observed in the forms of "major" and "minor" beta-thalassemia, rheumatic manifestations have almost never been described in the "minor" forms. We highlight the possibility of symptomatic osteoporosis as the first manifestation and we review the locomotive disorders associated to this hemoglobinopathy. PMID- 1623102 TI - [Rare manifestations of diabetic neuropathy]. AB - Up to 50% of diabetic patients develop neuropathies during their lives. Distal symmetric polyneuropathy is the most frequent variety, but there are other forms that are not exceptional and must be considered for the differential diagnosis of these patients. In this paper, the authors present three clinical cases of rare types of diabetic neuropathy: oculomotor cranial neuropathy (Case 1), diabetic amyotrophia (Case 2) and mixoide type with proximal asymmetrical locomotor neuropathy and distal polyneuropathy (Case 3). Their most relevant clinical characteristics are described, along with their differential diagnosis, evolution and therapeutical alternatives, in order to contribute to a better management of these patients. PMID- 1623104 TI - [Bronchial asthma. New ideas on pathogenicity and treatment]. AB - New insights on the pathogenicity of asthma have derived the attention to the inflammatory changes observed in the airways of asthmatic patients. The cellular and biochemical mechanisms that take place in them are not well enough understood and, thus, new questions have been added to the ones that existed before the asthma was considered an inflammatory disease. The interactions between cells and inflammation mediators, and between both of them and the autonomous control of the bronchial tree, are still adding new questions and preventing the working-out of a comprehensive theory explaining all the changes observed in asthma. In addition, the recent insights on the relationship between asthma, athopy and hereditary conditionings of both, have significantly increased our body of knowledge on the disease and have open new perspectives that now can be only foreseen. The new concepts related to the pathogenicity of asthma have placed the anti-inflammatory therapy in the first line of the anti-asthmatic therapy. The development of new agonists of the platelet activation factor, leukotriens or tromboxanes and the therapeutical strategies based on the control of IgE hypersecretion, may be relevant advances for the future control of this disease. PMID- 1623103 TI - [Thyrotoxic hypokalemic periodic paralysis]. AB - A case of palsy without family history associated to hyperthyroidism, is described. This is an rare entity in our environment (only two cases have been previously described) and may develop with hypo, normo or hyperkalemia. Its potential pathogenicity is discussed, which finally results in a disorder of the ionic interchange at the level of the muscle membrane. The need to identify these secondary forms of recurrent palsy is stressed, given that it may benefit from an adequate treatment. In the case presented here, the normalization of the thyroid function was followed by the sustained elimination of the muscle symptomatology. PMID- 1623105 TI - [2 new cases of male 46 XX syndrome]. PMID- 1623106 TI - [Stoke and idiopathic hypereosinophilic syndrome]. PMID- 1623107 TI - [De Quervain's subacute granulomatous thyroiditis: cause of fever of unknown origin]. PMID- 1623108 TI - [Hypoglycemia from a pleural fibrous tumor]. PMID- 1623109 TI - [Pure red cell aplasia associated with systemic lupus erythematosus]. PMID- 1623110 TI - [Septic arthritis from Streptococcus pneumoniae in rheumatoid arthritis]. PMID- 1623111 TI - Effects of the clotting process on endothelium-dependent relaxation of human middle cerebral artery. AB - Clotted blood decreased acetylcholine-induced relaxations of strips of human middle cerebral artery precontracted with noradrenaline, although histologically the endothelial layer was preserved. This effect was not prevented by catalase, superoxide dismutase or aspirin. Nifedipine reduced the decrease in acetylcholine induced relaxation. PMID- 1623112 TI - Annexins I to VI: quantitative determination in different human cell types and in plasma after myocardial infarction. AB - Concentrations of annexins I to VI were quantitatively determined in extracts of placenta and different human cell types. They were detectable in all extracts studied, but lymphocytes/monocytes, endothelial cells and fibroblasts had very high annexin contents. The results indicate cell type specific annexin repertoires. Annexins are intracellular proteins lacking signal sequences but which are detectable in trace amounts in plasma of healthy humans. The majority of plasma samples drawn from 14 patients suffering from myocardial infarction had elevated annexin III, IV and V concentrations. Shortly after infarction increased annexin levels were detected, reaching maximal values 24 to 48 h later. In the course of the following days annexin concentrations returned towards normal plasma levels. PMID- 1623114 TI - Improved lupus anticoagulant assay. PMID- 1623113 TI - Oral contraceptives caused thrombosis in a monoovular twin with protein C deficiency, while the other, without medication, remained asymptomatic. PMID- 1623115 TI - Thrombonostika F1.2. PMID- 1623116 TI - Bacterial lipopolysaccharide induces phosphatidylcholine breakdown in human leukaemia monocytic U937 cells. AB - We investigated the effect of bacterial lipopolysaccharide (LPS) on phospholipid (PL) turnover in human monocytic leukaemia U937 cells. Cells were pre-labelled with [3H]choline, [14C]ethanolamine and [3H]inositol for 24 h. By monitoring the radiolabel association with cellular PL, the data indicated that LPS (10 micrograms/ml) drastically altered the catabolism of choline-containing PL; it induced their breakdown by 50% within 20 min. The reutilization of choline or its phosphates for PL synthesis was also suggested as a result of regaining radiolabel in the next 40 min. Choline-containing PL then underwent a second degradation after 60 min; 50% decline in radiolabel was detected at 120 min. In contrast, LPS did not induce the breakdown of phosphatidylethanolamine and phosphatidylinositol through phospholipase C/phospholipase D (PLC/PLD). No significant redistribution of the radiolabel in PL was detected in any cases during chasing. The data clearly indicate that LPS stimulates phosphatidylcholine breakdown, implying that the liberation of phosphatidic acid or diacylglycerol via PLC/PLD reaction may be relevant to the initiation of LPS-induced monocytic activation. PMID- 1623117 TI - Measurement of crosslinked fibrin derivatives in patients undergoing abdominal surgery: use in the diagnosis of postoperative venous thrombosis. AB - Levels of plasma crosslinked fibrin derivatives, a sensitive and direct marker of the lysis of intravascular crosslinked fibrin, were measured serially in 135 patients undergoing major abdominal surgery to determine their behavior and their use as a screening test for postoperative venous thrombosis. Preoperative levels and levels on the first postoperative day were significantly higher by both enzyme immunoassay and latex assay in 31 patients who developed venous thrombosis (positive venography) than in 104 patients who did not (negative 125I fibrinogen leg scan). Preoperative XLFDP levels 400 ng/ml (enzyme immunoassay) had a sensitivity to the diagnosis of postoperative venous thrombosis of 58%, specificity 74%, positive predictive value 41% and negative predictive value of 85%. The sensitivity of XLFDP levels over 1200 ng/ml on the first postoperative day was 65%, specificity 73%, positive predictive value 38% and negative predictive value 89%. These cutoff values were chosen (high negative predictive value) to allow identification of patients who were unlikely to have venous thrombosis. Measurement of plasma XLFDP, a simple inexpensive test, could be used as a screen to select patients for surveillance procedures (IPG or duplex ultrasonography). A substantial increase in XLFDP levels (greater than 500 ng/ml) occurred in virtually all patients, suggesting that fibrinolysis is not 'shutdown' postoperatively and that these assays reflect lytic activity at the fibrin surface more accurately than do measurements of plasminogen activators and their inhibitors. PMID- 1623118 TI - The release of plasminogen activators (t-PA and u-PA) and plasminogen activator inhibitor (PAI-1) after venous stasis. AB - The aim of the present study was to compare plasma levels of urokinase-type plasminogen activator (u-PA), before and after 20 min of venous stasis, with those of tissue-type plasminogen activator (t-PA), type 1 plasminogen activator inhibitor (PAI-1) and t-PA/PAI-1 complexes, to determine whether both plasminogen activators and their inhibitor respond similarly to the same stimulus. We studied 36 patients with recurrent venous thrombosis in whom no coagulation defects predisposing them to thrombosis had been detected (mean age 38.2 years, range 15 70 years). Twenty healthy individuals (mean age 34.3 years, range 20-60 years) served as a control group. t-PA, PAI-1 and u-PA activity and antigen, as well as the t-PA/PAI-1 complex antigen, were measured before and after venous stasis. Post-stasis fibrinolytic parameters were corrected for the haemoconcentration which occurred during the venous occlusion test. Pathologically high PAI-1 levels (antigen and activity) were found in four out of 36 patients who were excluded from study. Functional and antigenic u-PA increased significantly after venous stasis when analysed as the absolute differences between paired samples (P less than 0.01). This increase in u-PA did not correlate with changes in t-PA or PAI-1 (r = 0.28 and r = 0.36 respectively). This leads us to suggest that different mechanisms relating to clearance and/or release from diverse sources might be involved in elevations of u-PA in response to a local endothelial stimulus. We conclude that venous stasis might not be the elective choice when evaluating 'bad responders' predisposed to thrombosis. PMID- 1623119 TI - Exploration of rapid bedside monitoring of coagulation and fibrinolysis parameters during thrombolytic therapy. AB - Monitoring coagulation parameters during thrombolytic therapy could be useful for prediction and treatment of haemorrhagic episodes. Technology based on dry reagent chemistry has been developed that allows rapid (less than 10 min) assays on small samples of whole blood. The assay principle is based on the restriction of motion of paramagnetic particles during fibrin polymerization, and subsequent liberation of particle motion during fibrinolysis. This technology was used to monitor prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen levels and fibrinolysis profiles during thrombolytic therapy with tissue plasminogen activator for acute myocardial infarction. The PT and aPTT obtained with the COAG-1 correlated well with conventional assays (r = 0.93 and 0.92 for PT and aPTT, respectively; p = 0.0001). Fibrinogen estimates, obtained by COAG-2 also correlated well with modified Clauss assays (r = 0.86, p = 0.0001). The rapid determination of the aPTT may improve management of adjunctive anticoagulant therapy following thrombolysis. The fibrinolysis profile may be useful during thrombolytic therapy to verify that a lytic state has been achieved, to monitor the lytic state throughout therapy, and to verify that the lytic state normalizes once therapy has been completed. PMID- 1623120 TI - Fibrinolysis factors and lipid composition of the blood in treated and untreated hypertensive patients. AB - The correlations between the cardiovascular risk factors hypertension, overweight, hyperlipidemia and fibrinolysis parameters were studied in a group of 54 otherwise healthy patients (age 19 to 70 years) with essential hypertension of moderate severity. Of the 54 patients 43 were treated with antihypertensive drugs and eleven were not. The patients included in this study who were treated with antihypertensive drugs were, in spite of their treatment, still hypertensive. Lipoprotein levels and fibrinolysis parameters did not differ between the untreated and treated patients. In the patient group we found significant incidence of hypertriglyceridemia (46%) elevated LDL-cholesterol (28%) and elevated lipoprotein (a) levels (43%). In comparison with a healthy control group the hypertensive patient group showed a decreased median tissue plasminogen activator activity (interquartile range): 0.23 (0.79) IU.10(3)/l vs 1.5 (0.47) IU.10(3)/l in the controls (p less than 0.0001), an increased tissue plasminogen activator antigen concentration: 8.2 (4.5) micrograms/l vs 5.1 (3.9) micrograms/l in the controls (p less than 0.0001), an elevated plasminogen activator inhibitor 1 level: 2.8 (2.5) AU.10(3)/l vs 1.1 (2.0) AU.10(3)/l in the controls (p less than 0.01) and a slightly increased alpha 2-antiplasmin concentration: 110 (8)% vs 98 (16)% in the controls (p less than 0.0001). Median D-dimer concentration levels were substantially increased in the hypertensive patients: 315 (263) micrograms/l vs 199 (146) micrograms/l in the controls (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623121 TI - Anticoagulants from marine algae. AB - Anticoagulant properties were first described in extracts from marine algae over 50 years ago. Currently over 60 species, representing the three major divisions of marine algae, have been reported to have such properties. The major active components are a variety of sulphated polysaccharides, some of which characterize as proteoglycans. These sulphated polysaccharides/proteoglycans exert antithrombin properties, primarily mediated by heparin cofactor II (HCII). However antithrombin III (ATIII) mediated anticoagulant activities, as well as an element of direct antithrombin activity, have also been observed. PMID- 1623122 TI - The Porton Medal Award in conjunction with the Haemostasis Club. PMID- 1623123 TI - Studies on the functionality of fibrinogen during rt-PA therapy: results of three different methods of fibrinogen determination. AB - The conversion of soluble fibrinogen to insoluble fibrin is a crucial event in the process of haemostasis. In the present study three different methods were used for the determination of plasma fibrinogen levels in 12 patients with acute myocardial infarction during rt-PA therapy. Two methods were based on fibrin formation and thus measured 'functional' fibrinogen: a clotting rate assay according to the Clauss method and a photometric polymerization rate assay. Thirdly, fibrinogen antigen was measured with a new enzyme immunoassay (EIA) for immunologically intact fibrinogen. The levels of functional and intact fibrinogen were strikingly different: 4.1 g/l (Clauss) and 3.6 g/l (photometric) vs 2.6 g/l (EIA) at baseline, 2.2 g/l (54% of preinfusion value) and 2.1 g/l (59%) vs 2.1 g/l (81%) at 90 min, 5.7 g/l (146%) and 4.5 g/l (130%) vs 2.7 g/l (106%) at 72 h. The rebound phenomenon exhibited by functional fibrinogen (130-150%) was not observed for levels of intact fibrinogen. A ratio was calculated of functional (Clauss method) to intact fibrinogen (EIA) for each individual patient and each time point. The mean ratio (n = 12 patients) was 1.6 at baseline, 1.0 at 90 min, and increased markedly between 8 and 24 h to a maximum of 2.1 (P less than 0.01). Our data indicate that the 'functionality', i.e. the clotting rate per unit concentration of circulating fibrinogen, changed during acute myocardial infarction and subsequent thrombolytic therapy. This is in keeping with data from literature that the relative amount of fast clotting high molecular weight (HMW) fibrinogen of total fibrinogen was increased in the initial phase of acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623124 TI - Peptide models for the membrane destabilizing actions of viral fusion proteins. AB - The fusion of enveloped viruses to target membranes is promoted by certain viral fusion proteins. However, many other proteins and peptides stabilize bilayer membranes and inhibit membrane fusion. We have evaluated some characteristics of the interaction of peptides that are models of segments of measles and influenza fusion proteins with membranes. Our results indicate that these models of the fusogenic domains of viral fusion proteins promote conversion of model membrane bilayers to nonbilayer phases. This is opposite to the effects of peptides and proteins that inhibit viral fusion. A peptide model for the fusion segment of the HA protein of influenza increased membrane leakage as well as promoted the formation of nonbilayer phases upon acidification from pH 7-5. We analyze the gross conformational features of the peptides, and speculate on how these conformational features relate to the structures of the intact proteins and to their role in promoting membrane fusion. PMID- 1623125 TI - Normal mode refinement: crystallographic refinement of protein dynamic structure applied to human lysozyme. AB - A new method of dynamic structure refinement of protein x-ray crystallography, normal mode refinement, is developed. In this method the Debye-Waller factor is expanded in terms of the low-frequency normal modes and external normal modes, whose amplitudes and couplings are optimized in the process of crystallographic refinement. By this method, internal and external contributions to the atomic fluctuations can be separated. Also, anisotropic atomic fluctuations and their interatomic correlations can be determined experimentally even with a relatively small number of adjustable parameters. The method is applied to the analysis of experimental data of human lysozyme to reveal its dynamic structure. PMID- 1623126 TI - Vibrational studies of the disulfide group in proteins. Part V. Correlation of SS stretch frequencies with the CCSS dihedral angle in known protein disulfide bridges. AB - Normal mode calculations have been done on 92 disulfide bridges in 25 known protein structures in order to correlate the SS stretch frequency with the CCSS dihedral angle. It is possible to classify the frequencies into four major categories, which provide a more detailed classification scheme than previously proposed from dialkyl disulfide correlations. PMID- 1623127 TI - A general approach for determining scalar coupling constants in polypeptides and proteins. AB - A general approach is described for measuring homo- and heteronuclear spin coupling constants in polypeptides and small proteins. This method uses selective magnetization transfer to generate cross peaks similar to exclusive correlated spectroscopy (E.COSY) and a large direct spin coupling (1J) in one dimension to "pull apart" cross-peak components by frequencies much larger than the resonance line width. A general description of this method is presented, along with a brief discussion of spin topology and relaxation effects that must be considered in designing multidimensional nmr pulse sequences for measuring vicinal coupling constants. The principles are demonstrated in designs of several two-dimensional nmr experiments for determining coupling constants in polypeptides and proteins. These include experiments for measuring 3J(HN-H alpha), 3J(H alpha i-1-15Ni), 3J(15N-H beta), and 3J(H alpha-H beta) coupling constants, which depend on the polypeptide dihedral angles phi, psi, and chi 1. Multidimensional nmr experiments developed with this approach will allow measurements of many vicinal coupling constants in peptides, proteins, and other molecules. Coupling constants measured in these spectra can be used to determine backbone and side-chain conformations, to obtain stereospecific resonance assignments of prochiral atoms, and to characterize conformational distributions of dihedral angles. Combined with information obtained from nuclear Overhauser effect measurements, these data will provide more precise determinations of protein solution structures by nmr spectroscopy. PMID- 1623128 TI - Studies on the yeast alpha-mating factor: a model for mammalian peptide hormones. AB - Small peptides initiate sexual conjugation in the yeast Saccharomyces cerevisiae and this phenomenon is an ideal paradigm for studying the mode of action of mammalian peptide hormones. 1H-nmr spectroscopy was used to examine the conformation of linear and cyclic analogues of the alpha-factor (WHWLQLKPGQPMY) in aqueous solution. In all cases peptides that exhibit nmr parameters expected for a type II beta-turn have higher biological activities than those that do not appear to assume this conformation. Based on a simple model for the interaction of the pheromone with its receptor, we prepared fragments of the alpha-factor. Several of these fragments either antagonize or potentiate the activity of the alpha-factor. The latter represent the first example of peptide fragments that synergize the activity of the parent pheromone. PMID- 1623129 TI - Conformation of uteroglobin fragments. AB - The conformation of three fragments of uteroglobin in aqueous solution and in the presence of SDS micelles is described. Two of these fragments correspond to helix II and helix III of uteroglobin, the crystal structure of which is made of four helices. The third peptide comprises helices II and III, with the connecting beta turn. While helix II does not interact strongly with the micelles, helix III adopts a rather clear alpha-helix in this system. The elongation of helix III with the addition of helix II at the N-terminus somewhat stabilizes the ordered structure. It is possible that the beta-turn found in the crystal is also present in solution. PMID- 1623130 TI - Conformational study of endothelins and sarafotoxins with the cystine-stabilized helical motif by means of CD spectra. AB - A series of CD measurements were carried out on members of peptides in the endothelin and sarafotoxin families. The helical structures taken by these peptides containing the helical motif with the sequences of Cys-X-X-X-Cys and Cys X-Cys [Y. Kobayashi et al. (1991) Neurochemistry International Vol. 18, pp. 525 534] are classified into three groups: a group of structures of ET-1, ET-2 and vasoactive intestinal contractor (VIC), a group of sarafotoxin, and a group of ET 3. PMID- 1623131 TI - Refinement of the thrombin-bound structure of a hirudin peptide by a restrained electrostatically driven Monte Carlo method. AB - Energy refinement of the structure of a linear peptide, hirudin56-65, bound to thrombin was carried out using a conformational search method in combination with restrained minimization. Five conformations originated from nmr data and distance geometry calculations having a similar global folding pattern but quite different backbone conformations were used as the starting structures. As a result of this approach, a series of low-energy conformations compatible with a set of upper and lower bounds of interproton distances determined from transferred nuclear Overhauser effects were found. A comparison among the lowest energy conformations of each run showed that the combination of energy refinement plus distance constraints led to a very well-defined structure for both the backbone and the side chains of the last 7 residues of the polypeptide. Furthermore, the low energy conformations generated with this technique contain a segment of 3(10) helix involving the last 5 residues at the COOH terminal end. PMID- 1623132 TI - Conformational analysis of an opioid peptide in solvent media that mimic cytoplasm viscosity. AB - Many neuropeptides exert their action between the presynaptic vesicles and postsynaptic transmembrane receptors, crossing different layers of specialized cytoplasm. Biomimetic media usually employed to study bioactive peptides do not reproduce the physico chemical environment of cytoplasm--in particular, the high viscosity of this biological fluid. Here we describe a conformational study of a delta-selective opioid peptide, deltorphin I, at variable temperatures in several biocompatible media characterized by varying values of viscosity and dielectric constant. It was found that only viscosity, among these parameters, induces ordered conformations; that is, it acts as a conformational sieve. This finding suggests that the high viscosity of the intersynaptic fluid contributes, in addition to the membrane catalysis proposed by Schwyzer, in overcoming the so called entropic barrier to the transition state of peptide-receptor interaction by selecting ordered conformations prior to receptor interaction. The folded conformer found in the 80:20 (v:v) DMSOd6/H2O cryoprotective mixture at 265 K has a shape consistent with those of rigid nonpeptidic opiates. PMID- 1623133 TI - Hydrophobicity-induced pK shifts in elastin protein-based polymers. AB - Three polypentapeptides--poly[0.8(GVGVP), 0.2(GEGVP)], poly[0.8(GVGIP), 0.2(GEGIP)], and poly[0.75(GFGVP), 0.25(GEGVP)]--all analogues of the polypentapeptide of elastin--(Val1-Pro2-Gly3-Val4-Gly5)n or poly(VPGVG)--have been prepared to determine the effect of changing the hydrophobicity, i.e., Val1- --Ile1 (I) and Val4----Phe4 (F), on the pKa and the temperature dependence of pKa of the Glu (E) residue. Shifts in pKa as large as 1.7 units are observed and the temperature dependence is much steeper for the structure-dependent proximity of the more hydrophobic Ile1 residues to the Glu4 residue. Even though this system is dominated by the inverse temperature transition of hydrophobically driven folding on raising the temperature, the effect of adding 0.15 N NaCl is to suppress the hydrophobicity-induced pKa shift. PMID- 1623134 TI - Stoichiometry of calcium binding to a synthetic heterodimeric troponin-C domain. AB - In this work we describe calcium binding to two synthetic 34-residue peptides, determined by 1H-nmr spectroscopy. The peptides investigated, SCIII and SCIV, encompass the calcium-binding sites III and IV, respectively, of troponin-C. In the absence of calcium it has previously been shown that each of these peptides possesses little regular secondary structure. Further, the 1H-nmr spectra of an equimolar mixture of both of these apo-peptides (apo-SCIII/SCIV) shows that little interaction occurs between peptides. Upon calcium binding the spectral changes that occur to SCIII/SCIV are consistent with global conformational changes in both peptides. We have shown previously that these conformational changes are a product of calcium binding to SCIII and SCIV to form a two-site heterodimer Ca2-SCIII/SCIV. It is proposed that this calcium-induced folding proceeds via calcium binding to SCIII to form Ca-SCIII, peptide association with apo-SCIV to form the heterodimer Ca-SCIII/SCIV, and calcium binding to form Ca2 SCIII/SCIV. The dissociation constants involved in this pathway, K1, Kd, and K2, respectively, have been determined by stoichiometric calcium titration of SCIII/SCIV, monitored by 1H-nmr spectroscopy. Using this procedure it has been determined that K1 = 3 microM, Kd = 10 microM, and K2 = 2 microM. PMID- 1623135 TI - Minimum energy conformations of proline-containing helices. AB - Proline occurs frequently in transmembrane alpha-helices of transport and receptor proteins even though statistical surveys demonstrate the overwhelming preference of this residue for a non-alpha-helical, hydrophilic environment. As a result, membrane-buried proline has been proposed to be functionally important, with function arising from structural discontinuity or destabilization of the helix. Destabilization may occur by Pro-mediated conformational transitions between discrete states, and may be manifested in membrane protein systems through reversible processes such as channel opening and closing or signal transduction. In this study, computer modeling of a model transmembrane alpha helix, (Ala)8-Leu-Pro-Phe-(Ala)8, in a medium of low polarity (dielectric = 2), is used to examine the occurrence and energetic accessibility of Pro-mediated conformational interconversions. Leu psi and chi 1, Pro psi, and Phe phi and chi 1 torsion angles were assigned random values so that a data base of 200 conformations for each of the cis and trans states was generated. The conformations were minimized and low-energy structures organized into families. This analysis demonstrated that the most populated lowest energy family is the Trans-I conformation, corresponding to proline in a kinked alpha-helix. Two additional trans structures, Trans-II and Trans-III, as well as a cis conformation, Cis-I, are also energetically competitive. Interconversions between the trans states could thus be mediated by changes at a single torsion angle, accompanied by minor local hydrogen-bonding rearrangements. This work substantiates that membrane-buried proline can provide the basis for conformational transitions between discrete alpha-helix-based structures in a nonpolar environment. PMID- 1623137 TI - The two-stranded alpha-helical coiled-coil is an ideal model for studying protein stability and subunit interactions. AB - We have designed de novo a two-stranded alpha-helical coiled-coil which consists of two identical 35-residue polypeptide chains arranged in a parallel and in register alignment. Their structure is stabilized by interchain hydrophobic interactions from hydrophobes at positions "a" and "d" of a repeating heptad sequence. The formation and stability of the coiled-coil is dependent on peptide concentration due to the monomer-dimer equilibrium. In contrast, that coiled-coil containing an inter-helical disulfide bond does not show any concentration dependence in the guanidine hydrochloride denaturation experiments as expected. Replacement of one large hydrophobic Leu residue in each chain with Ala significantly decreases coiled-coil stability in both the reduced and oxidized coiled-coils [decreases in transition midpoint of 1.6M (2.3-0.7) and 2.4M (5.3 2.9), respectively]. A large pH dependence on coiled-coil stability is observed over the pH range 4 to 7 (transition midpoints at pH 4, 5, 5.5, 6 and 7 were 3.8, 3.2, 2.0, 1.2 and 0.7M, respectively). The increasing stability with decreasing pH correlates with the protonation of the Glu acid side-chains and reduction of intrachain repulsions between Glu-Glu side-chains in positions i, i + 3 or i, i + 4 along each alpha-helix of the coiled-coil. In addition, coiled-coil stability increases with increasing ionic strength. PMID- 1623136 TI - Tyrosine-derived polycarbonates: backbone-modified "pseudo"-poly (amino acids) designed for biomedical applications. AB - Starting from L-tyrosine (Tyr) and its metabolites desaminotyrosine (Dat) and tyramine (Tym), four structurally related model dipeptides were prepared: Dat-Tym (neither N- or C-terminus present), Z-Tyr-Tym (N-terminus protected by benzyloxycarbonyl), Dat-Tyr-Hex (C-terminus protected by a hexyl ester group), and Z-Tyr-Tyr-Hex (both N- and C-termini present, protected by benzyloxycarbonyl and hexyl ester, respectively). The model dipeptides were used as monomers in the synthesis of polycarbonates. The polymerization reaction in the presence of either phosgene or triphosgene proceeded via the phenolic hydroxyl groups. Polymers with molecular weights of 105,000-400,000 da (by gel permeation chromatography, relative to polystyrene standards) were obtained. The physicomechanical properties (solubility, mechanical strength, glass transition and decomposition temperature, processibility) of the polymers were determined, and an attempt was made to correlate the polymer properties with the nature of the N- and C-terminus protecting groups. The presence of the urethane bond at the N-terminus protecting group was found to reduce solubility, ductility, and processibility, probably due to interchain hydrogen bonding. The presence of a C terminus alkyl ester group increased solubility and processibility. Thus, the most promising candidate polymer for biomedical applications was obtained from Dat-Tyr-Hex, the monomer carrying a C-terminus protecting group only. Since very similar results had recently been obtained for a series of structurally related polyiminocarbonates, the structure property correlations seem to be generally valid. PMID- 1623138 TI - The structure of Ro 09-0198 in different environments. AB - The constitution and configuration of Ro 09-0198 (cinnamycin) have been determined in DMSO. Further investigations in aqueous solution, in SDS micelles and in a lipid bilayer have been done to study the influence of different environments on the conformation of the peptide. It turned out that in spite of the polycyclic structure of the molecule, the conformation is drastically changed going from water to SDS micelles. Ro 09-0198 orients itself in lipid bilayers as expected from its amphiphilic structure. According to a nuclear Overhauser effect spectroscopy experiment under magic angle spinning (MAS) conditions, the molecule is incorporated into the membrane with its hydrophobic part inside the bilayer. PMID- 1623139 TI - Determination of the phi angle in a peptide backbone by NMR spectroscopy with a combination of homonuclear and heteronuclear coupling constants. AB - The phi angle in a cyclic peptide is determined by the combined use of homonuclear and heteronuclear coupling constants. Two of the four coupling constants that define the phi angle in a peptide are determined exactly, two qualitatively. Via Karplus-type equations, they are transformed into dihedral angles and a good agreement is found, allowing for a determination of the phi angle with a certain range of degrees. PMID- 1623140 TI - The structure of a rhombohedral R6 insulin hexamer that binds phenol. AB - Different hexameric forms of insulin have been crystallized from a variety of conditions. In the presence of 1% phenol, 1.0 M sodium chloride, and at a pH of 8.5, a rhombohedral form is produced with two monomers in the asymmetric unit, space group R3, a = 79.92 A and c = 40.39 A. The structure has been solved and refined, using data between 8.0 and 2.5 A resolution, to a residual of 0.157. Each of the monomers adopts an R conformation, that is residues B1-B8 are alpha helical. As a result of the T to R transition, an elliptical cavity is created between symmetry-related monomers and is occupied by a phenol molecule. A region of density within bonding distance to one of the zinc ions has been interpreted as an additional phenol molecule. PMID- 1623141 TI - NMR and CD studies of triple-helical peptides. AB - Triple-helix formation of the peptide (Pro-Hyp-Gly)10 was monitored by nmr and CD spectroscopy. The two-dimensional nmr spectra indicated that the Gly C alpha H and Pro C delta H proton resonances shift upfield in going from the nonhelical to helical form, while hydroxy-proline resonances are unchanged. The integrated areas of the helical and nonhelical resonances could be monitored in the one dimensional nmr spectrum, and indicate that in the (Pro-Hyp-Gly)10 about 90% of the residues are in a defined triple-helical conformation. The introduction of a glycine to alanine substitution or the deletion of a single hydroxyproline residue in the stable triple-helical peptide (Pro-Hyp-Gly)10 still allows trimers to be formed, but the trimers show a substantial loss of triple helix and decreased thermal stability compared with (Pro-Hyp-Gly)10. Two computer models were generated for the Gly----Ala peptide, one with the Ala side chains packed inside the helix and the other with the region containing the alanines forming a beta-bend that loops out from the helix. The nmr data is more consistent with the latter model. PMID- 1623142 TI - Characterization at atomic resolution of peptide helical structures. AB - A survey of literature for the various types of helices experimentally observed in high-resolution single crystal x-ray diffraction analyses of peptides has allowed to determine accurate conformational and helical parameters for the various secondary structures such as the alpha-helix, the 3(10)-helix, the fully extended conformation (2(5)-helix) and the beta-bend ribbon spiral. For each of these structures the characteristic phi, psi conformational parameters, n, the number of residues per turn, h, the height per residues and p, the pitch of the helix are described. PMID- 1623143 TI - Three-dimensional structure and active site of three hydrophobic molecule-binding proteins with significant amino acid sequence similarity. AB - We review our work on bovine and human retinol-binding protein (RBP), bovine beta lactoglobulin (BLG), and bovine odorant-binding protein (OBP). These three proteins share a sequence similarity high enough to justify the proposal that their three-dimensional structure ought to be quite similar, and they also share the function of similar or even identical hydrophobic ligand binding, although with a very different degree of specificity. Thus they constitute an ideal system to exhaustively explore the question of three-dimensional structure prediction from sequence similarity and the related question of binding site prediction for similar ligands. We have used x-ray diffraction techniques on single crystals of human and bovine RBP, bovine milk BLG, and bovine nasal mucosa OBP to investigate this problem. The results of these crystallographic studies indicate that to the level of resolution so far attained, the three-dimensional structure of these three proteins is reasonably predicted from the sequence similarity. The fold is the same and structural differences are rather subtle. Finally, we present experimental evidence that the binding sites of RBP, BLG, and OBP are in different regions of the molecules. Thus, it appears that although sequence alignment has correctly predicted the protein fold, it has incorrectly predicted the hydrophobic ligand-binding sites. PMID- 1623144 TI - Menopause: new indications and management strategies. AB - Postmenopausal women may benefit from estrogen replacement. In addition to the well-established treatment indications of vasomotor symptoms, genitourinary atrophy, and osteoporosis, studies also suggest improvement in psychologic well being and prevention of coronary heart disease. The potential cardioprotective effects of estrogen do not appear to be solely from alterations in lipid metabolism. Major risks of estrogen replacement including breast cancer continue to be a concern. Strategies of management including continuous estrogen and progestin regimens are reviewed. There exists an increasing body of evidence that successful treatment for estrogen-dependent tumors including endometrial carcinoma is not a contraindication to estrogen replacement therapy. The potential use of tamoxifen to relieve symptoms and prevent bone loss in women with breast cancer is suggested. PMID- 1623145 TI - Current status of in vitro fertilization and the new reproductive technologies. AB - The rapid pace of development and refinement of in vitro fertilization and ancillary assisted reproductive techniques warrants periodic review to keep the reader abreast of the growth in this clinical and scientific arena. Although not exhaustive, this review targets key areas of special interest and significance, including oocyte and embryo micromanipulation for assisted fertilization and genetic analysis, advances in the approach to ovarian stimulation, and examination of the scientific model afforded by ovum donation. PMID- 1623146 TI - Advances in reproductive toxicology. AB - Research in reproductive toxicology has relied on several animal models as well as on the more difficult-to-perform human studies. In animals, ovarian toxicity is being investigated in more detail, with investigation of characteristics of reversibility. Epidemiology studies using time-to-pregnancy techniques have been useful in identifying potential at-risk populations for further study. Male toxicology research has concentrated on defining normal sperm parameters in experimental animals and in men, particularly when those parameters are evaluated by computer-assisted techniques. PMID- 1623147 TI - New concepts in oral contraceptive pill use. AB - Over 30 years have elapsed since the introduction of the combination oral contraceptive pill. During this time, the estrogen and progestogen components of the pill have been reduced 80% and 90%, respectively. An improved understanding of the mechanisms involved in the metabolism of the oral contraceptive pill steroids now exists that allows us to better understand interactions of the pill with other drugs and medications. In an effort to reduce adverse reactions to the oral contraceptive pill, new progestogens have been developed for contraceptive pills soon to become commercially available. These issues as well as the concept of the pill-free interval are discussed in this review. PMID- 1623148 TI - Hyperandrogenism: new insights into etiology, diagnosis, and therapy. AB - Mutations in the genes for the insulin receptor, 21-hydroxylase, 11 beta hydroxylase, and 3 beta-hydroxysteroid dehydrogenase isomerase enzymes are associated with hyperandrogenism. These genetic causes of hyperandrogenism account for less than 10% of all cases. A major goal of future research will be to identify other genetic causes of hyperandrogenism. Evidence continues to accumulate that luteinizing hormone, insulin-like growth factor I, and insulin are major factors regulating ovarian androgen production. Optimal therapy for hyperandrogenism probably includes simultaneous suppression of androgen production and blockade of androgen action. PMID- 1623150 TI - Gynecologic surgery and endoscopy. PMID- 1623149 TI - Endometriosis: advances in understanding and management. AB - Endometriosis is a commonly encountered disease, yet most aspects of its pathogenesis, pathophysiology, and treatment remain controversial. Recent advances, however, have increased our understanding of this enigmatic disorder. While many theories persist regarding the pathogenesis of endometriosis, the transplantation hypothesis is by far the most widely accepted. Evidence continues to accumulate in support of this theory as the primary mode of generating ectopic endometrium. In addition, recent work has begun to uncover factors critical to the growth and maintenance of such implants. Advances in pathophysiology have strongly suggested a cause-effect relationship between endometriosis and pelvic pain; conversely, such a relationship between implants and infertility is becoming more tenuous. Treatment trials, in both animals and humans, have begun to clarify the role of specific interventions in combating endometriosis. In addition, as new pathophysiologic mechanisms have been proposed, an intriguing array of new modalities have been developed as treatment options. PMID- 1623151 TI - Infertility surgery: microsurgery. AB - Tubal and peritoneal factors continue to be a leading cause of infertility. In vitro fertilization, operative laparoscopy, and microsurgery are alternatives, but they are frequently complimentary therapeutic approaches. Proper investigation is the key to select the primary treatment modality. A well performed hysterosalpingography is most valuable in the initial assessment of the tubes and uterus. Hysterosalpingosonography, radionuclide hysterosalpingography, and falloposcopy are experimental investigative tools that may be useful in selected circumstances. Effective adjuvants to reduce postoperative adhesions continue to elude the surgeon and new substances are being experimented with. In proximal tubal obstruction, selective salpingography and tubal catheterization may differentiate cornual spasm from pathologic tubal occlusion and may be therapeutic when viscous material or endotubal synechia are the cause of obstruction. Microsurgery remains the effective approach for significant lesions such as salpingitis isthmica nodosa, endometriosis, obliterative fibrosis, and chronic follicular salpingitis. Distal tubal occlusion is amenable to treatment via either laparoscopy or microsurgery. The functional status of the oviduct appears to be the most important prognostic factor in subsequent pregnancy outcome. PMID- 1623152 TI - Falloposcopy. AB - This review discusses advances in falloposcopy over the past 10 years. Refinements in instrumentation, including fiberoptics, have allowed visualization of the endosalpinx, a portion of the reproductive tract that has evaded endoscopic evaluation. A coaxial system of falloposcopic placement may give way to a linear everting catheter that does not require hysteroscopic guidance. Tubal endoscopic applications are discussed, including correlating hysterosalpingogram findings with those findings at salpingoscopy. Endosalpingeal changes can be quantitated in the presence of hydrosalpinges, and possibly with endometriosis. A scoring system to measure changes has been described. Using this scoring system, endosalpingeal findings at salpingoscopy have been compared with histologic and electron microscopic findings. PMID- 1623153 TI - Gynecologic malignancy and surgery: from quantity to quality of life. AB - With modern anesthesia and better postoperative care, the mortality and morbidity of radical surgery have been markedly reduced during the last decades. With the maximum quantity of life achieved from radical surgery, increasing emphasis is now being placed on the quality of life. A better understanding of tumor biology and the consideration of different clinicopathologic factors that bear prognostic significance in therapeutic modalities will allow individualization of treatment. This will lead to less surgical morbidity and less functional and psychosexual impairments without sacrificing benefits of survival. PMID- 1623154 TI - Hysteroscopic surgery. AB - Because a wide variety of conditions can be diagnosed hysteroscopically, hysteroscopy has become a diagnostic gold standard. Through "operative" hysteroscopes, both the electrical current of the resectoscope and the energy of the neodymium:yttrium-aluminum-garnet laser have been effective tools in many cases and presented a new alternative to laparotomy and hysterectomy. The most frequent procedures are 1) endometrial ablation and partial endometrial ablation, 2) myomectomy for submucous myomas, 3) two-step myomectomy for large submucosal and intramural myomas, 4) hysteroscopic management of mullerian defects, and 5) hysteroscopic management of intrauterine adhesions. PMID- 1623155 TI - Embryoscopy: new developments in prenatal medicine. AB - Embryoscopy is a new technique that allows direct visualization of the embryo/fetus as early as the first trimester. A rigid fiberoptic endoscope is passed transcervically into the extracoelomic cavity and has been utilized to identify developmental milestones from weeks 4 to 8 following conception. All major external and internal structures develop during this period. With this technique, it is possible to both identify anomalies and confirm those diagnosed by ultrasound. Fetal blood sampling has also been preformed utilizing this technology and has established the feasibility of access to the human embryonic circulation. Future applications for embryoscopy include first-trimester prenatal diagnosis and therapeutic interventions such as gene or cell therapy at a time when the embryo is immunologically tolerant. PMID- 1623156 TI - Surgery for female urinary incontinence. AB - There has been very little advance in the surgery of female urinary incontinence over the past 20 years. In our opinion this is due to 1) uncritical acceptance of the intraabdominal pressure transmission theory, 2) uncritical acceptance of the concept of "detrusor instability," and 3) limited and uncritical evaluation of results of surgery. A new theory for female urinary incontinence is presented. This theory explains existing phenomena in terms of anatomic defects in the vagina and its supporting ligaments. Based on this theory, a new classification of female urinary incontinence and several new minimally invasive surgical procedures are briefly introduced. PMID- 1623157 TI - Reproductive endocrinology. PMID- 1623158 TI - Gynecologic surgery and endoscopy. PMID- 1623159 TI - Abstracts for the VIIIth Biennial Scientific Meeting, Asian-Pacific Association for the Study of the Liver. Seoul, Korea, 6-8 April 1992. PMID- 1623160 TI - Effects of diazepam and D-amphetamine on rhythmic pattern of eye movements in goldfish. AB - The effects of diazepam and D-amphetamine on spontaneous, vestibular- and visually-induced eye movements were studied in the restrained goldfish. These animals showed a stereotyped pattern of spontaneous eye movements that scanned the visual field in the horizontal plane. Fourier analysis of these eye movements revealed a rhythmic pattern of about 5 cycles per minute, whose frequency increased to double and decreased to half following treatment with diazepam and D amphetamine, respectively. However, the fast and slow components of vestibulo ocular and optokinetic reflexes, as well as peculiar blink-like movements, remained unchanged at the same drug doses. These results suggest the presence of a central pattern generator for spontaneous eye movements in the goldfish, whose oscillation frequency is pharmacologically modifiable. PMID- 1623161 TI - Phorbol ester and lignocaine or pentobarbitone interactions at presynaptic axons. AB - The interaction between anaesthetics and protein kinase C activation was studied in unclamped field currents from unmyelinated axons which give rise to en passant synapses. Electrical responses could be resolved into Na, K and Ca components revealed by electrode polarisation pretreatment with blockers of K-conductances. In the presence of phorbol dibutyrate, there was an increase in the potency of lignocaine, pentobarbitone and tetrodotoxin: for the Na current, the potency increased by 2.67 +/- 0.64, 2.35 and 2.47 fold respectively. The potentiation does not appear to be any indirect result of changed membrane potential. It is suggested that protein kinase C phosphorylation of membrane channel proteins increases the effectiveness of these substances. PMID- 1623162 TI - Pre-treatment with a Ca2+ channel antagonist facilitates vestibular compensation. AB - A single injection of the Ca2+ channel antagonist verapamil (0.4 or 0.8 mg kg-1, i.m.) was given to adult guinea-pigs 1 h before a unilateral labyrinthectomy and the effects on the compensation of spontaneous ocular nystagmus (SN) were measured. At the 0.8 mg kg-1 dose, pre-treatment with verapamil significantly reduced SN frequency compared to saline controls; however, it also reduced the rate of SN compensation, resulting in no significant difference in the time required to reach maximal compensation. These results suggest the possibility that voltage-dependent Ca2+ channels may be involved in vestibular compensation. PMID- 1623163 TI - Modification induced in visual cortical activity of rat by neonatal monocular enucleation. AB - Monocular enucleation was performed on rats at birth. The animals were raised and from the age of 3 months the evoked activity was tested in the contralateral visual cortex both by mapping of evoked potentials and by autoradiography. It was found that monocular enucleation changed the distribution of the evoked activity characteristically. The focus of activity shifted laterally and was restricted to the binocular part of the primary visual cortex, while hardly any evoked activity or labelled neurons were found in its medial part. PMID- 1623164 TI - A K+ current in Xenopus muscle cells which shows inactivation. AB - The purpose of this study was to describe an inactivating potassium current that is present in Xenopus muscle cells in culture. Whole cell currents were recorded from muscle cells grown in culture for 16-30 h. The majority of muscle cells had an outward current which inactivated during a 100 ms maintained depolarization. The outward current was reduced by tetraethylammonium or the aminopyridines, but not completely eliminated by either agent. Depolarizing prepulses reduced both the peak current and the late component of the current. The results suggest that by one day in culture these skeletal muscle cells develop an inactivating outward potassium current. PMID- 1623165 TI - Function-blocking antibodies against cholinergic neuronal differentiation factor. AB - Cholinergic neuronal differentiation factor, CDF, causes a transition from noradrenergic to cholinergic phenotype in cultured sympathetic neurons. Moreover, its identification with leukemia inhibitory factor has shown that CDF is a multifunctional cytokine. To examine the physiological role of CDF and to further elucidate the as yet unknown effects of CDF on the nervous system, two kinds of function-blocking antibodies were generated. One type, raised against whole native CDF, completely blocks CDF activity, whereas the other type, raised against a synthetic peptide corresponding to the N-terminal amino acid region of CDF, blocks activity partially. All three anti-CDF and two antipeptide polyclonal antibodies tested in this study significantly inhibit CDF function. PMID- 1623166 TI - A rostrocaudal gradient in the synthesis of enkephalin in nucleus accumbens. AB - A subpopulation of projection neurons in the nucleus accumbens uses the neuropeptide enkephalin as a neurotransmitter. The synthesis of enkephalin in striatal neurons is regulated by dopaminergic inputs. In the present study quantitative in situ hybridization histochemistry was used to examine the effects of unilateral 6-hydroxydopamine lesions of the ascending dopaminergic fibres on levels of enkephalin mRNA in subregions of the nucleus accumbens. It was found that the levels of enkephalin mRNA were increased throughout the nucleus after the lesion. However, the increase appeared to be much higher in rostral parts of the nucleus than in caudal parts, indicating regional differences in the effects of blockade of the dopaminergic neurotransmission. Possible causative factors for these differences are discussed. PMID- 1623167 TI - A role for interleukin-2 in the regulation of striatal dopaminergic function. AB - The present study determined whether interleukin-2 (IL-2) is endogenous to the normal adult rat striatum and whether IL-2 regulates striatal dopaminergic tone. IL-2 mRNA (1.5 kb size), endogenous IL-2 and IL-2 receptors were found to be distributed throughout the rat striatum in moderate densities. Application of exogenous IL-2 to striatal slices in in vitro produced significant increases in both spontaneous and potassium (25 mM)-evoked [3H] dopamine release. The modulatory effect of IL-2 was dependent on the presence of external calcium and required axonal nerve activity, since IL-2 was unable to increase transmitter release under low external calcium conditions or in the presence of tetrodotoxin. Overall, this study indicates that IL-2 may be an endogenous neurokine that regulates striatal dopaminergic function in normal animals. PMID- 1623168 TI - Isolated p65 protein reproduces membrane binding activity of synaptic vesicles. AB - Purified synaptic vesicles are highly enriched with a protein which binds cell plasma membranes. The binding is selective for acidic phospholipids and sialoglycosphingolipids. In partition chromatography of vesicle proteins, the binding activity was co-eluted with a limited set of proteins. Among them the most abundant species were two vesicle-specific proteins: p65 and synaptophysin. In affinity chromatography of vesicle proteins, only p65 bound to a column of immobilized lysoganglioside. The same protein, purified by preparative electrophoresis, retained the binding activity and fully reproduced the hemagglutinating property and the selectivity for acidic lipids of whole vesicles. The results suggest that the (hemagglutinating) lipid binding properties of the vesicles are mainly if not exclusively due to p65. PMID- 1623169 TI - CRF increases protein phosphorylation and enhances retention performance in rats. AB - This study examines the roles of PKC and protein phosphorylation in the retention performance of a passive avoidance learning (PAL) task in rats. Results revealed that H7 injected into the dentate gyrus (DG) of the hippocampus impaired retention in a dose-dependent manner. Corticotropin-releasing factor (CRF) injected into the DG improved retention and this facilitation was antagonized by H7 pretreatment. CRF increased phosphorylation of five proteins, whereas H7 decreased phosphorylation in three of these proteins in both the cytosol and the membrane fractions of hippocampus. These effects were shown not to be associated with stress. These results demonstrate that CRF increased protein phosphorylation associated with enhanced retention of PAL task in rats. PMID- 1623170 TI - Subcortical mechanisms in orientation sensitivity of cat visual cortical cells. AB - The orientation biases seen in the responses of neurones of the dorsal lateral geniculate nucleus (dLGN) can be reduced by the local application of the GABA antagonist, bicuculline methiodide. This fact was exploited to investigate whether these biases are important for cortical orientation selectivity by measuring the orientation sensitivity of cortical cells before and during iontophoretic administration of bicuculline in the topographically corresponding region of the dLGN. This procedure led to a significant reduction in the orientation sensitivity of the cortical cell. The results suggest that subcortical orientation biases are at least partly responsible for the orientation sensitivity seen at the level of the striate cortex. PMID- 1623171 TI - Slow modulation of EEG. AB - Time variation of the successive 2.5 s long EEG theta and alpha band powers during 5 min rest and 4 min hyperventilation (HV) was analyzed by modified Wigner distribution (WD) in 22 subjects. Two main peaks at frequency 0.02 Hz and 0.068 Hz were detected in the WDs of both alpha and theta powers at rest. The HV increased the magnitude of the faster (0.068 Hz) component of both theta and alpha WD's while the slower (0.02 Hz) component was increased only in the theta WD. We hypothesize that this slow brain activity reflects spontaneous periodic changes of cortical excitability with control at the brain stem level. PMID- 1623172 TI - The hippocampo-septal projection in mice: long-term potentiation in the lateral septum. AB - In anaesthetized young mice, the fimbria was stimulated and field potentials were recorded ipsilaterally in the lateral septum (LS). Evoked responses were typically characterized by a two-component negative wave (N2 and N3) followed by a low amplitude positive wave. The amplitudes and latencies were highest and shortest respectively in the dorsal LS for the N3 component and in the ventral LS for the N2 component. Tetanic stimulation of the fimbria induced long-term potentiation (LTP) only in the case of the N3 component. The differential changes in N2 and N3 following tetanic fimbrial stimulation are discussed in the context that the dorsal LS appears to exhibit a higher density of LTP-mediating receptors. PMID- 1623173 TI - Whole-cell membrane current and membrane resistance during hypoxic spreading depression. AB - In rat hippocampal tissue slices we recorded extracellular potential (Vo) and whole-cell patch clamp current of CA1 pyramid cells. During hypoxic spreading depression (SD)-like depolarization, the holding current (Ih) increased sharply. Membrane 'slope' resistance (Rm) decreased to 10-67% (mean 39%) of the resting value. The SD-related membrane current (ISD) reversed near zero mV. With voltage dependent K+ and Na+ currents blocked by Cs+ and QX-314, shifts of Ih and decrease of Rm during SD were not suppressed. We conclude that hypoxic SD of CA1 pyramidal cells is associated with a large non-selective inward current through yet to be identified membrane mechanisms, which cannot fully explain the SD related Vo shift. PMID- 1623174 TI - Alpha 1-antitrypsin and alpha 1-antichymotrypsin are in the lesions of Alzheimer's disease. AB - We performed immunocytochemistry to localize alpha 1-antichymotrypsin and alpha 1 antitrypsin in tissue sections of Alzheimer disease patients. Our results show that both serine protease inhibitors are localized in neurofibrillary tangles and senile plaques. Using various monoclonal and polyclonal antibodies, immunolabeling was evident in formalin, methacarn or acetone-fixed sections. Brief pretreatments of sections with either formic acid or guanidine-HCl were also necessary to reveal clear immunostaining of the lesions with two of the antibodies. We suggest that both alpha 1-antitrypsin and alpha 1-antichymotrypsin may be functionally involved in the pathogenesis of the lesions of Alzheimer's disease. Like alpha 1-antichymotrypsin, the major cell producing alpha 1 antitrypsin is likely to be astrocytes since the protein was localized there and astrocytes are involved in both lesions. PMID- 1623175 TI - Impaired acquisition of the Morris water maze following global ischemic damage in the gerbil. AB - Five minutes of global ischemia in the Mongolian gerbil impaired acquisition of a Morris water maze task when testing began 72 h after surgery. In spite of extensive damage to CA1 pyramidal cells, ischemic animals eventually learned to locate a submerged platform and performed normally on a subsequent retention test. Animals that were allowed a more protracted recovery period (21 days) acquired the task as readily as control gerbils. These results suggest that undamaged structures within and external to the hippocampal formation allow spatial learning to proceed at a somewhat reduced rate. PMID- 1623176 TI - Prolactin similar to ectopic pituitary isograft restores responsiveness in Snell dwarf mice. AB - The effects of ovine prolactin (PRL) (2 x 5 IU a day) and an ectopic pituitary isograft on the responsiveness were examined using locomotor and exploratory activities as measures in PRL-growth-hormone-thyrotropin-deficient Snell dwarf mice (dw/dw). After 5 weeks of treatment, both PRL and the graft restored the two behavioural measures to normal levels. Results clearly demonstrate the involvement of PRL in global behavioural responsiveness and suggest a possible role for PRL in the changes induced by the graft. PMID- 1623177 TI - The carboxy-terminal extension of the D1-precursor protein is dispensable for a functional photosystem II complex in Chlamydomonas reinhardtii. AB - The D1-precursor protein of the photosystem II reaction centre contains a carboxy terminal extension whose proteolytic removal is necessary for oxygen-evolving activity. To address the question of the role of the carboxy-terminal extension in the green alga Chlamydomonas reinhardtii, we truncated D1 by converting codon Ser345 of the psbA gene into a stop codon. Particle gun transformation of an in vitro modified psbA gene fragment also carrying mutations conferring herbicide resistance yielded a homoplasmic transformant containing the stop codon. Since oxygen evolution capacity is not affected in this mutant as compared with herbicide-resistant control cells, the carboxy-terminal extension is dispensable for a functional photosystem II complex under normal growth conditions. PMID- 1623178 TI - Functional analysis of the regulatory region of a zein gene in transiently transformed protoplasts. AB - The transcription of zein genes in maize is tissue-specific and developmentally regulated. The 5' regulatory region of many zein genes contains two promoters, P1 and P2, lying approximately 1000 bases apart. The promoter/enhancer activity of various fragments of the two promoter regions of the zein gene E19 have been analysed by means of transient expression experiments. The results indicate that the various regions differentially affect the expression of the GUS reporter gene activity in protoplasts from tobacco leaves, maize immature endosperms and in vitro endosperm cell cultures. In tobacco protoplasts only the proximal promoter region, P2, activates GUS expression, while in endosperm culture cells only the distant promoter, P1, gives significant activity. The P1 region, both in direct and opposite orientation, stimulates a low level of GUS expression in protoplasts from immature endosperms. PMID- 1623179 TI - Isolation and characterization of a gene encoding a chlorophyll a/b-binding protein from mustard and the targeting of the encoded protein to the thylakoid membrane of pea chloroplasts in vitro. AB - Three independent clones carrying a mustard gene coding for the chlorophyll a/b binding protein were isolated by screening a genomic library of mustard with a heterologous cDNA probe from pea. All of them encode the same CAB gene, which, as shown by sequence analysis and comparison with published CAB sequences, belongs to the family of type I PSII CAB genes, encoding a precursor protein of 266 amino acids. Several conserved sequence motifs are observed in the 5' and 3' non-coding region of the gene. The putative transcription start site could be localized to 60 bp upstream of SA-CAB1 initiator codon by S1 mapping. Plasmids were constructed which allow in vitro transcription and translation of the whole chlorophyll a/b-binding protein and of truncated species which lack increasing portions of the C-terminus. Whereas the in vitro import into pea chloroplasts is not affected by these C-terminal deletions, targeting to the thylakoid membrane is abolished by the removal of the C-terminal helical domain. Accordingly, the 54 amino acids which contain the C-terminal membrane-spanning helix and flanking regions is an essential component of the thylakoid targeting signal. PMID- 1623180 TI - Construction and characterisation of a yeast artificial chromosome library containing three haploid maize genome equivalents. AB - We have constructed a yeast artificial chromosome (YAC) library using high molecular-weight DNA prepared from agarose-embedded leaf protoplasts of the maize inbred line UE95. This library contains 79,000 clones with an average insert size of 145 kb and should therefore represent approximately three haploid genome equivalents. The library is organised as an ordered array in duplicate microtitre plates. Forty-one pools of DNA from 1920 individual clones have been prepared for rapid screening of the library by the polymerase chain reaction (PCR). Using this approach, together with conventional colony hybridisation, we have been able to identify between one and eight positive clones for every probe used. PMID- 1623181 TI - Combination of in vitro capping and ribonuclease protection improves the detection of transcription start sites in chloroplasts. AB - A primary transcript from the chloroplast rpl32 gene was labelled at its 5' end using a capping enzyme and [alpha-32P]GTP followed by hybridization to a cold RNA probe. A RNase protection assay gave a clear protected band and its initiation site of transcription could thus be estimated, which had not been possible by using DNA probes. The combination of in vitro capping and RNase protection is an excellent method for mapping transcription initiation sites on the chloroplast genome and shows a high improvement relative to the DNA-employing strategies. PMID- 1623182 TI - Sequence analysis and developmental expression of an alfalfa protein disulfide isomerase. PMID- 1623183 TI - Nucleotide sequences of two cDNA clones encoding different Cu/Zn-superoxide dismutases expressed in developing rice seed (Oryza sativa L.). PMID- 1623184 TI - Sequence analysis of five new field isolates demonstrates that the chain length of potato spindle tuber viroid (PSTVd) is not strictly conserved but as variable as in other viroids. AB - The sequence analysis of five new field isolates of potato spindle tuber viroid (PSTVd) of different virulence revealed that the length of their RNA chain is not strictly conserved to 359 nucleotides (nts), as one could have inferred from the previously sequenced PSTVd strains. It was now found that the chain length is strain-specific like in the case of practically all other viroids, and that it may vary, so far, between 356 and 360 nts. Taking our previously sequenced and least virulent mild strain PSTVd KF6-M as standard, the new mild strains PSTVd WA M and PSTVd F-M differ from it by one or two nts. The new intermediate-severe strains PSTVd F-IS and PSTV-F 88-IS differ from the standard mild strain by eight and nine nts, respectively, whereas the new severe-lethal strain PSTVd F-SL differs in seven nts. Most of these mutations are located within the virulence modulating (VM) region and within the variable region (VR), and only in two strains a single mutation is found in the right terminal domain. PMID- 1623185 TI - Nucleotide sequence of the rice (Oryza sativa) Em protein gene (Emp1). PMID- 1623186 TI - Complete nucleotide sequence of a sorghum gene coding for the phosphoenolpyruvate carboxylase involved in C4 photosynthesis. PMID- 1623187 TI - Amino acid sequence of the N-terminal domain of yam (Dioscorea japonica) aerial tuber acidic chitinase. Evidence for the presence of a wheat germ agglutinin domain in matured acidic chitinase from unstressed tuber. AB - The amino acid sequence of the N-terminal domain of acidic chitinase from unstressed aerial tuber was determined and proved the presence of an N-terminal domain in acidic chitinase. The amino acid sequence was determined on a pyroglutamylaminopeptidase-treated N-terminal fragment of V8 protease and on chymotryptic peptides of this fragment. The sequence determined revealed 8 residues deletion and 2 residues insertion as compared with the N-terminal domain of tobacco basic chitinase. The N-terminal domain determined showed a homology of 40% and 52% with the N-terminal domain of tobacco basic chitinase and wheat germ agglutinin, respectively. PMID- 1623188 TI - Conserved relationship between psbH and petBD genes: presence of a shared upstream element in Prochlorothrix hollandica. AB - Prochlorophytes are an unusual group of prokaryotic oxygenic photoautotrophs that morphologically appear to bridge the gap between cyanobacteria and the chloroplasts of eukaryotic plants. Molecular data place this group evolutionarily within the cyanobacteria, but they have a photosynthetic apparatus that is very similar to that found in chloroplasts. We have sequenced from the prochlorophyte Prochlorothrix hollandica a set of genes (psbB, psbH, petB and petD) that has a conserved organization in chloroplast genomes that is different from the organization in cyanobacterial genomes. The four genes are linked as an operon in chloroplasts, but only petB and petD are closely linked and cotranscribed in cyanobacteria. Although the prochlorophyte gene arrangement resembles that of cyanobacteria, one feature suggests the coordinated regulation of the unlinked genes. A 93 bp region of absolute conservation occurs upstream of the psbH gene and the petBD operon, near the site of transcription initiation in each gene set. This conserved element may indicate an alternative to cotranscription for achieving co-regulation of the psbH and petBD genes in the prochlorophyte. PMID- 1623189 TI - Cloning and characterization of a gene involved in phytoene synthesis from tomato. PMID- 1623191 TI - Molecular basis for novel root phenotypes induced by Agrobacterium rhizogenes A4 on cucumber. AB - We have used the wild-type Agrobacterium rhizogenes strain A4 to induce roots on cucumber stem explants. Cultures of transformed roots obtained that were capable of hormone-autonomous growth could be grouped in three phenotypic classes. Of particular interest were extremely thick roots of a type not previously described. Characterization of the transferred DNA and of the expression of the corresponding genes allowed us to determine that the genes rolABC of the TL region of the Ri plasmid are sufficient to induce thin roots similar to those observed in other species, while the aux genes of the TR region are sufficient to induce thick roots. Among clones bearing the aux genes, there was a correlation between level of expression of aux2 and root phenotype. PMID- 1623190 TI - Structure of the pine (Pinus thunbergii) chlorophyll a/b-binding protein gene expressed in the absence of light. AB - A gene for chlorophyll a/b-binding protein (cab) of pine (Pinus thumbergii) was isolated and sequenced. The gene (cab-6) contains an intron at a position equivalent to the type II cab genes of angiosperms. Transcript mapping analyses show that the amount of the mRNA in the dark is about half of that in the light. The cab-6 gene is expressed in dark-grown seedlings at a very high level, differing from angiosperm cab genes which are induced by light. The cab-6 gene typifies the coniferous plant cab genes in light-independent gene expression. PMID- 1623192 TI - Molecular cloning of a cDNA encoding aspartate aminotransferase-P2 from lupin root nodules. AB - Two isoenzymic forms of aspartate aminotransferase are present in the plant fraction of developing lupin root nodules. One of these forms, aspartate aminotransferase-P2 (AAT-P2), increases dramatically with the onset of biological nitrogen fixation and is associated with the assimilation of ammonia by the plant in the Rhizobium-legume symbiosis. A day 18 lupin nodule cDNA library in the lambda ZapII vector was immunoscreened with a monoclonal antibody specific for AAT-P2 and yielded two near-full-length 1700 bp clones. These clones were sequenced. Amino acid sequences from three peptides derived from immunopurified AAT-P2 were aligned, and showed 100% homology with the amino acid sequence deduced from the cDNA clones. The DNA sequence showed 50% homology with AAT sequences from a range of animal sources. Conversion of the clones to the phagemid form allowed their expression in Escherichia coli where both exhibited enzyme activity that could be immunoprecipitated with AAT-P2-specific monoclonal antibodies. Western blot analysis revealed protein moieties with molecular masses of 39, 43, 45 and 55 kDa. The 5' end of the clones coded for a hydrophobic leader sequence of about 50 amino acids indicative of a targeting sequence and consistent with the plastid localisation of nodule AAT-P2. PMID- 1623193 TI - Nucleotide sequence of a gene from Arabidopsis thaliana encoding a myb homologue. AB - A gene encoding a proto-oncogene, a myb-related gene named Atmyb1, was cloned from Arabidopsis thaliana, and its nucleotide sequence was determined. The Atmyb1 gene contains an intron of 494 bp, and there are no highly homologous sequences present in the A. thaliana genome, but evidence was found that other myb-related genes exist. In the 5' flanking region, we found several typical cis-acting elements found in plant promoters. Sequence comparisons revealed that the ATMYB1 protein has a putative DNA-binding domain with two repeats of tryptophan clusters, which is common in MYB-related proteins in plants, while animal MYB related proteins contain DNA-binding domains with three repeats of tryptophan clusters. The putative DNA-binding domain of the ATMYB1 protein has higher homology with that of the human c-MYB protein than with those of other plant MYB proteins. PMID- 1623194 TI - An alfalfa cDNA encodes a protein with homology to translationally controlled human tumor protein. PMID- 1623195 TI - Complete nucleotide sequence of the 22 kDa coat protein of Andean potato mottle virus. PMID- 1623196 TI - Nucleotide sequence of the mitochondrial 18S rRNA gene from lupine (Lupinus luteus). PMID- 1623197 TI - Construction of in-frame chimeric plant viral genes by simplified PCR strategies. AB - The use of polymerase chain reaction (PCR)-based mutagenesis to create chimeric genes is presently not cost-effective because of the size and number of primers as well as the number of PCRs required. We have developed two strategies based on inverse PCR that exploit limited homologies between two DNA molecules to create in-frame chimeric plant viral genes. This report also contains a compilation of information useful for determining possible restriction sites at a given common dipeptide coding motif between any genes of interest. PMID- 1623198 TI - Nucleotide sequence of a cDNA encoding an Arabidopsis cyclophilin-like protein. PMID- 1623199 TI - Structure and sequence of a dehydrin-like gene in Arabidopsis thaliana. PMID- 1623200 TI - Isolation of a gene from maize encoding a chlorophyll a/b-binding protein. PMID- 1623201 TI - The nucleotide sequence of the rDNA spacer region between the 25S and 18S rRNA genes in a species of the genus Vicia, V. hirsuta. PMID- 1623202 TI - Isolation and sequence analysis of a cDNA clone encoding ethylene-forming enzyme in Brassica juncea (L.) Czern & Coss. PMID- 1623203 TI - The cell-cell channel in the control of growth. AB - Several lines of evidence indicate that the cell-cell channels in gap junction are conduits for growth-regulating signals. Experimental upregulation of the channels by retinoids causes inhibition of cellular growth and, conversely, their downregulation by oncogenes, e.g. activated src, stimulates growth. In either direction, the extent of growth correlates tightly with the degree of communication. Cogent evidence of the channel's function in growth regulation is now on hand: incorporation of a channel-protein gene into the genome of a transformed communication-deficient cell line normalizes communication and growth. The current data conform to a model of growth control with discrete regulatory centers. PMID- 1623204 TI - Classical cadherins. AB - Cadherins represent a gene family of Ca(2+)-dependent cell adhesion molecules (CAMs) identified during development and in adult organs. They generally mediate cell-cell adhesion by homotypic interaction, although heterotypic binding between different cadherin molecules is possible. Molecular cloning and sequence comparison has led to the characterization of a highly homologous group of 'classical' cadherins and more distantly related members, together composing a gene superfamily. The classical cadherins are transmembrane glycoproteins which exhibit, in addition to the structural homologies, a very similar overall protein topology. Protein sequence comparison has led to the identification of domains of common functional importance. The cytoplasmic domains of cadherins associate with peripheral cytoplasmic proteins termed catenin alpha, beta and gamma with molecular weights of 102, 88 and 80 kDa respectively. This complex formation seems to regulate the adhesive function of cadherins, most likely by connecting cadherins with actin microfilaments. Possible implications of catenins for cadherin function are discussed. PMID- 1623205 TI - Structure and interactions of desmosomal and other cadherins. AB - The cadherin superfamily of cell-cell adhesion molecules is now known to include proteins of the desmosome as well as of the adherens type of junction. The desmosomal cadherins consist of two families of proteins, the desmocollins and the desmogleins, both of which are represented by different isoforms which are differentially expressed in epidermis. The desmocollins are quite similar to the classic cadherins in overall structure, but with alternatively spliced variants; the desmogleins have extra cytoplasmic sequences added onto the basic cadherin structure. The cytoplasmic domains are specialized for binding to 'mediator' proteins, such as plakoglobin, which interconnect to the intermediate filament system rather than the actin filaments as do the classic cadherins. PMID- 1623206 TI - Cell adhesion in invasion and metastasis. AB - Metastatic cells exhibit considerable flexibility in their adhesive interactions with other cells or components of the extracellular matrix. This review will describe the involvement of specific adhesion receptors, extracellular matrix molecules and cell dissociating cytokines in the metastatic cascade. We will particularly focus on disturbance of intercellular adhesion as a prerequisite for the release of invasive cells from carcinomas. We suggest that cell dissociation in these tumours is accomplished by loss of function or expression of the epithelial cell adhesion molecule E-cadherin, and through the activity of cell motility factors such as the scatter factor. PMID- 1623207 TI - Immunoglobulin superfamily: structure, function and relationship to other receptor molecules. AB - The immunoglobulin superfamily includes the most diverse group of receptors known. They are united by the possession of a common structural feature, the immunoglobulin homology domain. They are found in species from insects to man. They are central to both the humoral and cell mediated immune reactions; they serve as cell surface receptors responsible for positional ques during embryonic development, as well as viral and growth factor receptors. They function in conjunction with other receptor families including the integrins and selectins. Thus, they are frequently parts of adhesive cascades and as such activate signal transducing systems required for the expression or activation of other cell surface receptors. They continue to be the targets of intense investigation into the molecular basis of adhesive interactions. PMID- 1623208 TI - NCAM: structural diversity, function and regulation of expression. AB - NCAM is a large family of structurally closely related proteins with cell-cell adhesive properties and a temporo-spatially regulated expression throughout development. This review covers recent work on NCAM with an emphasis on the still open questions of the full extent of structural diversity and the mechanism whereby it arises, the chemistry and functional consequences of the binding event and the intricacies of the developmental regulation of NCAM, all of which have ramifications in its likely role as an effector of morphogenesis. PMID- 1623209 TI - Selectins: cell surface lectins which mediate the binding of leukocytes to endothelial cells. AB - The selectins are the most recently identified family of cell adhesion molecules. The three known members of this family (L-, E- and P-selectin) mediate the binding of leukocytes to endothelial cells and are involved in the homing of lymphocytes to lymph nodes, as well as the extravasation of neutrophilic granulocytes into inflamed tissues. The lectin character of these cell adhesion molecules (CAMs) makes the selectin protein family unique among all known CAM families. The review will summarize present knowledge about the structural organization, the ligands identified (carbohydrates and glycoproteins) and the different regulation mechanisms of the cell surface activity of the three selectins. PMID- 1623210 TI - Local therapy of malignant pleural effusion with mitoxantrone. AB - Twelve patients received intrapleural instilments of the cytostatic agent mitoxantrone in a total dosage of 30 mg for locoregional palliative therapy of malignant pleural effusion. Effusion could be stopped for a mean period of 3.2 months in 11 patients. PMID- 1623211 TI - Clinical pharmacokinetics of ifosfamide in combination with N-acetylcysteine. AB - The pharmacokinetics of ifosfamide were studied in 20 patients with soft tissue and bone sarcomas. Drug was administered as a 30-60 min i.v. infusion at 1.2 or 2.0 mg/m2/day for five consecutive days. Some patients also received 1.5 g/m2 of N-acetylcysteine (NAC) administered 3 times per day during the course of therapy. NAC had no effect on ifosfamide pharmacokinetics. There were significant differences in plasma half-life, area under the concentration-time curve and plasma clearance on day 1 versus day 5 of ifosfamide administration. Myelosuppression and granulocytopenia correlated better with day 1 versus day 5 ifosfamide pharmacokinetics suggesting that the alteration of ifosfamide pharmacology with multiple dosing has a significant effect on drug activity. PMID- 1623212 TI - Effects of the Ru(III) complexes [mer-RuCl3(DMSO)2Im]degrees and Na[trans RuCl4(DMSO)Im] on solid mouse tumors. AB - The effects of two new Ru(III) complexes, [mer-RuCl3(DMSO)2Im] degrees and Na[trans-RuCl4(DMSO)Im], were investigated on primary tumor growth and on the survival time using three solid metastasizing tumors of the mouse: Lewis lung carcinoma, B16 melanoma and MCa mammary carcinoma. Na[trans-RuCl4(DMSO)Im] appears to be the most promising compound, in that: (1) it is soluble in water and therefore easy to handle in comparison with the neutral species [mer RuCl3(DMSO)2Im]degrees or to the already described BBR2382; (2) similarly to cisplatin, though at a lower level, it reduces tumor growth in its primary site in each tumor model employed; (3) unlike cisplatin, it increases the life span of tumor-bearing hosts in all tumors used, independently of the effects on primary tumor growth; and (4) it is also effective in reducing spontaneous metastasis formation when the effects on primary tumor growth are completely absent. Dimethylsulfoxide (DMSO), used for solubilizing poorly water-soluble compounds (i.e. [mer-RuCl3(DMSO)2Im]degrees) or for stabilizing the compound in the solution before injection (i.e. Na[trans-RuCl4(DMSO)Im]), reduces the anti-tumor potency. Conversely, the antitumor effects of Na[trans-RuCl4(DMSO)Im] are more pronounced in mice hydrated with isotonic saline. We conclude that Na[trans RuCl4(DMSO)Im] is a good candidate for further investigations aimed at ascertaining the mechanism of the anti-metastatic activity and of the positive effects on survival time of mice bearing solid metastasizing tumors. PMID- 1623213 TI - Relationship between tumor histopathology and in vitro sensitivity to antitumor drugs in gastric cancer. AB - The in vitro drug sensitivity of gastric cancer tissues obtained from 40 patients with advanced cancer was compared in terms of the pathological classifications which were assigned according to the General Rules for the Gastric Cancer Study in Surgery and Pathology in Japan. Cases of poorly differentiated adenocarcinoma which had penetrated the serosa were evaluated using the succinate dehydrogenase inhibition (SDI) test for determining the in vitro chemosensitivity. The sensitivity of the stage III group to cisplatin was higher than that of the stage IV group. Although there were no statistical differences in drug sensitivities according to macroscopic findings (Borrmann's classification), the expanding growth type was more susceptible that the infiltrating type to cisplatin, aclacinomycin A (ACR) and carboquone (CQ) microscopically. In cases of lymph node metastasis [n(+)] the sensitivity to cisplatin, ACR, CQ, adriamycin and mitomycin C was less than in those with or without primary lymph node metastasis [n(-)]; lymphatic invasion in the gastric wall (ly) was a significant factor linked to drug resistance. Our findings indicate that the evaluation of tumor pathology is important in predicting the chemosensitivity of poorly differentiated gastric cancers. PMID- 1623214 TI - Effects of intravesical Corynebacterium parvum on recurrences of superficial tumors of the urinary bladder. AB - We studied 96 patients with superficial tumors of the urinary bladder treated by transurethral resection in order to investigate the value of intravesical Corynebacterium parvum (CP) to prevent recurrences. In 52 cases, two vials (2 ml, 4 mg CP) diluted in 60 ml buffer saline were intravesically administered weekly 12 times and then monthly for a period of 2 years. All patients were studied in a 3 year follow-up by cytology, histology and endoscopy. Recurrences were observed in 21.1% of cases in the CP treated group and in 54.5% of cases in the untreated group. CP immunostimulation is less effective in preventing recurrences in patients with malignant cells as indicated by urine smears in the post-operative period. Morphological changes of the bladder wall due to CP administration in patients without recurrences are described. Chronic lymphocyte infiltrate appears to be an essential event for the action of CP as an adjuvant therapy in urinary bladder cancer. PMID- 1623215 TI - Preclinical activity of ilmofosine against human tumor colony forming units in vitro. AB - Ilmofosine (BM 41.440, 1-hexadecylthio-2-methoxymethyl-rac-glycero-3 phosphocholine) is a synthetic alkyl lysophospholipid analog with activity against a variety of tumor models in vitro and in vivo. The i.v. form is presently undergoing early clinical investigation in phase I trials. In order to help define types of tumors that might be clinically sensitive to this agent we have studied the anti-tumor effects of ilmofosine against a variety of freshly explanted human tumor specimens using an in vitro soft agar cloning system. Final concentrations of 1.0-30 microgram/ml were used in continuous incubations experiments. Of 348 specimens tested, 134 (39%) were evaluable for determination of tumor growth modulating activity. The most common tumor types recruited included non-small cell lung, breast, colorectal, ovarian, renal cell cancer and melanoma. A concentration-dependent increase in the frequency of inhibited tumor specimens was observed with 6/134 (4%) sensitive specimens at 1 microgram/ml as compared with 113/133 (85%) sensitive specimens at 30 micrograms/ml (p less than 0.0000005). We conclude that ilmofosine is active against a variety of tumors in vitro. Clinical phase II trials with ilmofosine including the tumor types with in vitro sensitivity are warranted if adequate plasma concentrations of this agent can be reached in patients. PMID- 1623217 TI - The anti-neoplastic activity of 2,3-dihydrophthalazine-1,4-dione and N-butyl-2,3 dihydrophthalazine-1,4-dione in human and murine tumor cells. AB - 2,3-Dihydrophthalazine-1,4-dione derivatives demonstrated potent cytotoxicity against the growth of murine leukemia cells and human single cell suspension, i.e. Tmolt3 leukemia and HeLa-S3, as well as colon adenocarcinoma and KB nasopharynx. However, only select compounds demonstrated activity against bronchogenic lung, osteosarcoma and glioma growth. 2,3-Dihydrophthalazine-1,4 dione was active in vivo against L1210 leukemia, Lewis lung and Ehrlich ascites carcinoma growth. In L1210 cells the agents inhibited both DNA and RNA synthesis, and a few of the compounds were capable of inhibiting protein synthesis at 3 times their ED50 values. When 2,3-dihydrophthalazine-1,4-dione and N-butyl-2,3 dihydrophthalazine-1,4-dione were examined for their mode of action in the L1210 lymphoid leukemia cells, the sites of inhibition by the agents appear to be the de novo purine pathway at the enzymes IMP dehydrogenase and PRPP amido transferase. IMP dehydrogenase activity was inhibited at least 45% by 45 min at 100 microM concentration of drugs whereas the remaining enzymes that were affected by the drugs were not inhibited as early. Secondary sites were dihydrofolate reductase and thymidylate synthetase. The d(NTP) levels were also reduced specifically dATP and dCTP levels. PMID- 1623216 TI - Dose response and toxicity of doxorubicin microspheres in a rat tumor model. AB - The therapeutic response and toxic effects of chemotherapy using several doses of doxorubicin in conventional solution form or bound to an ion-exchange resin were compared in a rat tumor model, to assess the relationship of drug dose to therapeutic efficacy and associated toxicity. Single bolus injections of 3.0, 4.5, 6.0, 7.5 and 9.0 mg/kg were administered via the abdominal aorta to rats bearing hindlimb tumors. Tumor size was measured serially and the growth rates of treated groups were compared with a control growth curve. In addition, the effect of empty microspheres on tumor growth rate was assessed. The levels of circulating white blood cells were measured and compared to control levels to provide an indication of the severity of bone marrow toxicity experienced by each form of treatment. Finally, any difference in the distribution of doxorubicin to tumor, hindlimb and cardiac tissue following administration of doxorubicin as free drug or on microspheres was ascertained. Empty ion-exchange resin exerted a small although significant detrimental effect on tumor growth which may be explained by the embolization of microspheres in the precapillary blood vessels of the tumor resulting in a transient delay in tumor growth rate. The lowest dose of doxorubicin produced a significantly better therapeutic response when administered in the free drug form, but higher doses elicited an equivalent delay in tumor growth for both drug microsphere and free drug groups in a dose dependent manner, with the maximum anti-tumor response occurring at the highest dose. Treatment with free doxorubicin at high doses resulted in significant reductions of circulating white blood cells suggesting the occurrence of bone marrow toxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623218 TI - 9-Hydroxybenfluron: effect on energy-yielding processes in Ehrlich ascites and P388 murine leukemia cells. AB - The main purpose of the present investigation was to study the effect of 9 hydroxybenfluron (HBF) on aerobic glucose consumption, lactic acid formation, content of total (T-SH) and non-protein thiol groups (NP-SH), endogenous respiration and levels of ATP in both Ehrlich ascites and P388 murine leukemia cells. The lowest concentrations of HBF significantly stimulated both glucose consumption and lactate formation in Ehrlich ascites cells. HBF decreased the level of both T-SH and NP-SH in Ehrlich cells. However, the decrease in the level of NP-SH was significantly higher. Both respiration and ATP levels were inhibited more markedly in Ehrlich than in P388 cells. In P388 cells a significant decrease in ATP level (67%) was noted only at the highest concentration of HBF (100 mumol/l). PMID- 1623219 TI - Anti-tumor properties of the organometallic complex cis dimethylbis[sulfinylbis[methane]-S]platinum(II). AB - The water-soluble organometallic complex cis-[Pt(Me)2(Me2SO)2] (Me = methyl; Me2SO = dimethyl sulfoxide) (cis-dimethyl platinum(II); CDMP) was evaluated for its toxicity on the rat and for its efficacy against two tumors of this animal: the Yoshida ascites sarcoma and the T8 sarcoma of Guerin. The lethal dose for 50% of normal animals was 46.4 mg/kg; the predominant toxic effects were loss of weight, decrease in leukocytes and necrosis of the kidneys after i.v. or of the liver after i.p. administration. Doses of drug varying from 2 to 40 mg/kg were administered once by i.p., i.v., i.m. and intra-tumor (i.t.) route from 1 to 7 days after i.p. injection of 10(6) Yoshida ascites sarcoma cells and s.c. implantation of approximately 300 mg of T8 sarcoma of Guerin. The compound showed anti-tumor activity increasing both the average life span and survival of the rats. A comparison between the therapeutic properties of the title complex with those of cis-[PtCl2(NH3)2] (CDDP) reveals that cis-dimethyl platinum(II) exhibits the same anti-tumor activity associated with 6 times reduced toxicity. PMID- 1623220 TI - Lipophorin lipase from the yolk of Manduca sexta eggs: identification and partial characterization. AB - In the hawkmoth Manduca sexta high density lipophorin from adult insects (HDLp-A) delivers lipids to developing oocytes. During this lipid delivery HDLp-A is taken up by the oocyte and converted to a very high density lipophorin (VHDLp), which is stored in protein storage granules (yolk bodies). A membrane-free lysate of isolated M. sexta yolk bodies was demonstrated to contain lipoprotein lipase activity that hydrolyses the diacylglycerol of HDLp-A. With HDLp-A as a substrate yolk body lipophorin lipase (YBLpL) activity was shown to be maximal between pH 9 and pH 9.5. NaCl concentration was optimal between 0.7 M and 1 M. YBLpL activity required neither bovine serum albumin nor calcium ions but appeared to be stimulated by 5 mM EDTA. Diisopropyl fluorophosphate effectively inhibited YBLpL activity, indicating the presence of a serine in the active site of the enzyme. The identified lipase activity co-eluted with lipophorins and vitellins from the yolk in the void volume of a Sephadex G-75 gel filtration column. This observation suggests that the lipase has a Mr of more than 80,000, or that the enzyme is associated with the lipoproteins. Incubation of HDLp-A with yolk body lysate converted HDLp-A to two classes of higher density lipophorins. The highest density lipophorins produced during this incubation approached the density of VHDLp as it is isolated from mature eggs. The possible role of YBLpL activity in the delivery of lipids to developing oocytes is discussed. PMID- 1623221 TI - Serum alanine aminotransferase levels among volunteer blood donors: effect of sex, alcohol intake and obesity. AB - Serum alanine aminotransferase (ALT) activity and antibody to hepatitis B core antigen (anti-HBc) were proposed as surrogate markers of non-A, non-B (NANB) infection. In this study we analyzed 649 consecutive repeat blood donors to define the possible exclusion rate if both surrogate markers were implemented in our Blood Service, and to assess risk factors associated with elevated ALT levels. One hundred and seven blood donors (16.5%) had slightly elevated ALT levels (higher than the upper reference value, but less than twice this level), but only 15 (2.3%) had a level higher than mean log + 2.25 SD. Seventy-seven (11.8%) resulted anti-HBc positive. Blood donors with elevated ALT levels and those who were anti-HBc positive belonged to different populations, being only 6 (0.9%) positive for both surrogate markers. Only two known donors (0.3%) resulted anti-HCV positive, and each of them was implicated in one of the four post transfusion hepatitis (PTH) cases observed in 200 recipients of blood from these 649 donors. Both were negative for anti-HBc but one had elevated ALT levels. Male sex, age, alcohol use and obesity resulted all independently and significantly associated with elevated ALT levels. For both alcohol use and body weight we observed a significant linear relationship with serum ALT levels. These findings suggest that in our Region the exclusion of blood donors with ALT levels above the reference value, or those anti-HBc positive, would exclude an unacceptably high rate of blood donors without proven evidence of post-transfusion hepatitis prevention.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623222 TI - Treating chronic liver disease: lessons from a day hospital. AB - The relationship between the professional background of the physician requesting the biopsy procedure (whether non-specialist or specialist in hepatology/gastroenterology) and the subsequent decision of treatment of the patients was analyzed. Treatment was divided into two categories named arbitrarily "no therapy" (general supportive measures) or "therapy" (causal treatment based on active drugs or measures aimed at affecting the cause of the disease). Of the 204 cases of outpatient needle biopsies available for study, 157 were made by specialist request and 47 were made by a non-specialist request. Sixty-eight (43%) of the former, but only 3 (2%) of the latter had "therapy" (p = 0.0001). Also, patients in which histology showed chronic active liver disease had "therapy" more frequently (49 of 109, 44.9%) than those without chronic active liver disease (22 of 95, 23%) with p less than 0.01. However, patients with histological active chronic disease were not more frequent among specialist requests (56.6%) than among the non-specialist requests (42.5%). But among patients attended by the specialist, there were more patients (31.8%) with positive serum markers of Hepatitis B virus infection than among those sent by others (12.7%) with p less than 0.01. We conclude that at least in the premises in which this study was carried out, blind liver biopsies will lead to active treatment more often in patients treated by a specialized physician, because these patients are more likely to have a virus identified as the cause of their liver disease and consequently will receive antiviral treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623223 TI - Anticonvulsant-induced chronic pancreatitis. A case report. AB - We report the case of a young man suffering from epilepsy who developed chronic calcified pancreatitis after ten years of therapy with the anticonvulsant drugs carbamazepine and phenytoin. Long-term anticonvulsant drug therapy may have a contributory role in the development of chronic pancreatitis by chronic stimulation of cytochromes P-450. PMID- 1623224 TI - Endoscopy and gastroenterology. PMID- 1623225 TI - Italian Association for the Study of the Liver. XXV annual meeting. Rome, June 18 19, 1992. Abstracts. PMID- 1623226 TI - Experimental endoscopic subcutaneous surgery. AB - Endoscopic techniques have found increasing applications in general surgery. In this article, an attempt has been made to utilize endoscopy via a subcutaneous approach in an experimental pig model for dissection of fat, muscle, and fascia. PMID- 1623227 TI - New drug interventions in Alzheimer's disease. PMID- 1623228 TI - Coma, intracranial pressure, intensive care, head injury and neoplasia. PMID- 1623229 TI - Long-term head injury problems. AB - Areas of current research in the nature and remediation of the long-term sequelae of traumatic brain injury (TBI) are reviewed. Studies identifying features that predict outcome still greatly outnumber those of efficacy of rehabilitation. A growing interest is in acute biochemical change that may exacerbate poor outcome. PMID- 1623231 TI - Neuropsychology, dementia and aging. PMID- 1623230 TI - Cerebrovascular disease. PMID- 1623232 TI - Disorders of cerebrospinal fluid circulation and edema. AB - An assessment of contemporary techniques for the diagnosis and management of hydrocephalus and brain edema are reviewed. Further refinements in magnetic resonance imaging (MRI) techniques may aid in the selection of patients with normal pressure hydrocephalus (NPH) who respond to shunting. PMID- 1623233 TI - Paediatric neurosurgery. AB - Surgical disorders of the central nervous system of children differ significantly from those of adults. The management of these disorders requires an integrated multidisciplinary practice of paediatric specialists in an appropriate paediatric environment. An increasing number of neurosurgeons are now restricting themselves to this field resulting in the more effective diagnosis and treatment of children with neurosurgical disorders. PMID- 1623234 TI - The early management of head injury. AB - Acute management involves triage, well directed investigation and timely surgical intervention when necessary. All are discussed in this review. Cerebral blood flow (CBF) and flow velocity assessment are among the other investigations mentioned. Other topics include paediatric head injury, cerebrospinal fluid (CSF) fistulae, stab wounds and post-traumatic epilepsy. PMID- 1623235 TI - Protection against ischaemia: the basis of acute stroke therapy. AB - The search for effective therapy of acute stroke, centres on the two strategies of restoring blood flow before ischaemia causes irreversible infarction, and moderation of the biochemical changes in ischaemic tissue that cause neuronal death. This review concentrates on the role of lactacidosis, calcium ions, free radicals, and excitatory neurotransmitters in the pathogenesis of neuronal death, and on the therapeutic possibilities in acute stroke emerging from studies in animal models. PMID- 1623236 TI - The cardiac factor in stroke. AB - Cardiac disorders associated with cerebral embolism including cardiac surgery, myocardial infarction, endocarditis and non-valvular atrial fibrillation (NVAF) are reviewed along with methods to detect cardioembolic sources. Warfarin and aspirin are effective in the primary prevention of stroke in NVAF but the relative efficacy remains to be determined. PMID- 1623237 TI - Rheology and strokes. AB - Further evidence is presented that rheological abnormalities antedate stroke and are not just a consequence of stroke. Whether these abnormalities should be corrected in the acute phase after stroke is still uncertain. Until more data are available haemodilution is not to be recommended in most cases of acute stroke. PMID- 1623238 TI - Imaging in cerebrovascular disease. AB - High-resolution structural imaging of ischemic lesions now enables the assignment of complex ischemic clinical symptoms to cortical and subcortical lesions. Functional imaging shows some new features of cerebral ischemia which can be directly investigated in the individual patient. Vascular imaging is rapidly improving with the introduction of magnetic resonance angiography (MRA). Today its diagnostic value is unsettled but promising, in particular if used in combination with other techniques like ultrasonography and positron emission tomography (PET). PMID- 1623240 TI - Neuropsychology, dementia and aging. PMID- 1623239 TI - Clinical trials in cerebrovascular disease. AB - Randomized clinical trials provide the most reliable evidence of the risks and benefits of a treatment or management plan. Often it is necessary to have information from many thousands of patients in a clinical trial to know how to manage the next patient in the clinic. Recent trials in stroke prevention will change clinical practice by the more appropriate use of carotid endarterectomy and the use of anticoagulation in non-rheumatic atrial fibrillation. Other studies have indicated that modification of risk factors, such as decreased salt consumption, is important. Despite many new trials there is still no proven treatment for acute ischaemic stroke. To provide reliable evidence on the risks and benefits of treatment of acute stroke we need much larger randomized controlled trials. PMID- 1623241 TI - Neuropsychology of vision. AB - A selection of the literature on vision published in the last 2 years from various neuroscience disciplines is reviewed. It is organized around the notion of independent processing mechanisms for sensory cues such as wavelength, intensity and orientation; these are subsequently integrated for the perception of colour, brightness and contours, for example, which then feed into higher order systems for visual recognition (words and objects) and visuospatial cognition. A strict hierarchical system is, however, not plausible. Apart from the physiological evidence against such a concept, the widespread observations of 'knowledge without awareness' suggest direct links between different levels, which by-pass conscious experience. PMID- 1623242 TI - Neurology of developmental dyslexia. AB - Developmental dyslexia has until recently been considered to belong solely in the domain of educational psychology. With the advent of better theories on language and reading, and better methods for assessing the structure and function of living human brains and for determining genetic transmission, dyslexia is now poised to become a focal concern of cognitive neuroscience and genetic research. Recent findings from neuroanatomy, neurophysiology, neuropsychology, and genetics research are reviewed. PMID- 1623243 TI - Neurology of memory. AB - This review discusses the neurological basis of human memory focusing on brain behavior relations as revealed in patients with memory disorders due to brain lesions. A few relevant animal studies are also discussed. Recent studies are reviewed that provide new insights into the anatomic, chemical, and psychological organization of memory in health and neurological diseases. PMID- 1623244 TI - Amyloid, dementia and Alzheimer's disease. AB - Senile plaques (SP) and neurofibrillary tangles (NFT) are the major histopathological changes that occur in Alzheimer's disease (AD). How these two different types of lesions are related to each other and to the dementia of AD is unknown. Recent studies lead to paradoxical conclusions: NFT and neuronal alterations such as synapse loss are much more closely related to the symptoms of dementia than are SP. However, mutations in the beta-amyloid protein of SP have been found in some patients with familial AD, suggesting that an abnormality in amyloid causes the development of SP, NFT and AD dementia. Examination of transgenic animals that produce amyloid precursor protein (APP), or altered forms of APP, may lead to the development of an animal model of AD, and ultimately to answers that link amyloid production to neuronal alterations, and cognitive impairments. PMID- 1623245 TI - Epidemiology and genetics of multiple sclerosis. AB - Epidemiological data suggest an aetiological role for both genetic and environmental factors in multiple sclerosis (MS), but these have yet to be fully characterized. It is probable that MS susceptibility is determined by polygenes but specific loci need to be identified. PMID- 1623246 TI - Virus-induced demyelination in man: models for multiple sclerosis. AB - Epidemiologists have long worked at the limit of their powers to invoke an infectious agent to explain some of the epidemiological features of multiple sclerosis (MS). No virus has yet been definitively assigned a causal role in the pathogenesis of MS. Many viruses, however, have been incriminated, but it has not been possible to reproduce every single observation. Nevertheless, important lessons have been learned from the quest to identify such agents. Other kinds of demyelinating disease within the central nervous system (CNS) have been clearly linked to direct or indirect effects of viral infection. An understanding of the pathogenesis of these models affords possible insights into the mechanisms by which viruses or other agents might be operative in MS and other chronic diseases of the nervous system. PMID- 1623247 TI - Immunology of multiple sclerosis. AB - Recent advances in the understanding of the immunology of multiple sclerosis (MS) are discussed. In the central nervous system (CNS) major histocompatibility complex (MHC) class I and II antigens, and lymphocyte adhesion molecules are expressed. Furthermore, there are cells present which produce important effector molecules such as interferon (IFN)-gamma and tumor necrosis factor (TNF). A role for myelin antigen-specific autoimmunity is supported, but not proven, by the presence of a marked quantitative increase of T and B cells with such specificities, enriched to the CNS. Several myelin antigens, as well as a multitude of peptide parts of these, are apparently recognized. It will be of interest to study the functional abilities of these cells and how they are regulated. PMID- 1623248 TI - Pain and disorders of consciousness. PMID- 1623249 TI - Clinical epilepsy. AB - Advances in the understanding and treatment of human epilepsy published in the preceding year are discussed. The review focuses on three topical areas: epidemiological studies pertinent to clinical management decisions; new information on the pathophysiology and genetics of human epilepsy; and new information on vagal nerve stimulation as a potential treatment for medically intractable epilepsy. PMID- 1623250 TI - Pain mechanisms and the management of neuropathic pain. AB - The nociceptive system is not fixed, but changes in response to its input and activity. This 'plasticity' comprises dynamic developments of both pro- and antinociceptive processes. Recent advances in the understanding of these processes have important implications for the treatment of persistent neuropathic pain. PMID- 1623251 TI - Sleep disorders. AB - Advances in knowledge of brain regulation of sleep and wakefulness have led to greater understanding of the effects of such diseases as narcolepsy and sleeping sickness on brain function. Treatment of the two most common sleep disorders, insomnia and obstructive sleep apnea syndrome (OSAS), is often but not always effective; promising new approaches are under investigation. PMID- 1623252 TI - Infections and demyelinating disease. PMID- 1623253 TI - Pain and disorders of consciousness. PMID- 1623254 TI - Parkinson's disease: clinical and therapeutic aspects. AB - Recent developments on the clinical and therapeutic aspects of idiopathic Parkinson's disease (IPD) have focused on the role of monoamine oxidase B inhibition in IPD, strategies to manage the long-term levodopa (L-dopa) syndrome and attempts to replace nigral tissue by grafting. In addition, tools for community screening and possible identification of an 'at-risk' as well as presymptomatic population of sufferers have been suggested. PMID- 1623255 TI - Pathogenesis of Parkinson's disease. AB - The importance of genetic aspects, ageing, environmental factors, head trauma, defective mitochondrial respiration, altered iron metabolism, oxidative stress and glutamatergic overactivity of the basal ganglia in the pathogenesis of Parkinson's disease (PD) are considered in this review. PMID- 1623256 TI - The dystonias. AB - The various dystonias have been found in at least five different hereditary backgrounds. The gene responsible for one of the dystonias, idiopathic torsion dystonia (ITD), lies on chromosome 9q32-34, with flanking markers now 1-2 cM apart. Magnetic resonance imaging and computerized tomography (CT) abnormalities in the basal ganglia, especially in the putamen, are found in many secondary dystonias. Botulinum toxin therapy is proving very useful in the treatment of focal dystonias. PMID- 1623257 TI - Tics and myoclonus. AB - This article describes advances occurring over the last year in the pathophysiology, etiology and treatment of tics and myoclonus. Progress is being made in the clinical definition of Tourette syndrome (TS). The search for the TS gene has already excluded more than 50% of the autosomal genome. Progress in the understanding of myoclonus is slow but continuous. Several paper are devoted to clinical aspects but much recent attention has been focused on the pathophysiological mechanisms underlying myoclonus. PMID- 1623258 TI - Non-parkinsonian tremor. AB - Tremor may be seen not only in association with Parkinson's disease but also as an idiopathic disorder or in association with a variety of neurologic diseases. Our knowledge of these associations and of effective treatments for various types of tremor has increased. PMID- 1623259 TI - Genetic considerations in movement disorders. AB - Certain genetic aspects of the movement disorders, including parkinsonism, dystonia, ataxia, chorea, tics, and others, are reviewed. Clinical features, diagnostic techniques, and laboratory tests of newly recognized inherited syndromes are discussed. Progress in linkage analysis in several disorders is also presented. PMID- 1623260 TI - The impact of intensive neonatal care on the frequency of mental and motor handicap. AB - Recent outcome data on infants who were born extremely premature and who required extracorporeal membrane oxygenation (ECMO) are reviewed with particular reference to the design of follow-up studies. It is suggested that outcome data are an important medical audit measure. PMID- 1623261 TI - Migrational disorders of the brain. AB - Migrational disorders are the result of a wide range of fetal diseases that become manifest before midgestation. Recognition may not tell us everything about the etiology of these disorders, but it certainly tells us their time of origin. More diagnostic clues may be added to the case of an individual patient if the type of migrational disorder is taken into consideration. PMID- 1623262 TI - Epileptic encephalopathies of early childhood. AB - The epileptic encephalopathies of infancy and childhood include West syndrome, Lennox-Gastaut syndrome, severe myoclonic epilepsy of early childhood and related syndromes. The exact limits of these syndromes are still a subject of debate. The clinical features include several types of brief, frequently repeated seizures associated with mental retardation. The causes are multiple and brain malformations and dysplasias play an important role. Treatment remains unsatisfactory and the place of surgery seems limited. PMID- 1623263 TI - Neurological diseases in disorders of organic acids. AB - Organic acidemias remain a significant cause of mortality and morbidity, particularly resulting in neurological sequelae. The rapid recent expansion of technology has resulted in significant advances in the diagnosis of the disorders, but it can still be quite difficult. Recognition of specific features on neuroimaging can complement the biochemical and clinical assessment. Disorders of fatty acid oxidation have recently been recognized. It has become apparent that they occur more frequently and with a much wider clinical and biochemical spectrum than previously thought. PMID- 1623264 TI - New concepts in the diagnosis and treatment of lysosomal and peroxisomal disorders. AB - For the 36 known lysosomal disorders the main diagnostic advance is the identification of the gene defect with the demonstration of heterogeneity for each. Therapies that involve enzyme replacement or bone marrow transplantation are evolving. An increasing number of peroxisomal disorders are being identified. Combined liver-kidney transplantation are beneficial for hyperoxaluria type I, and dietary therapy and bone marrow transplantation appear to benefit patients with X-linked adrenoleukodystrophy. PMID- 1623265 TI - Multiple sclerosis in childhood. AB - The occurrence of multiple sclerosis (MS) in childhood is described. An increasing number of cases with onset before puberty have been published. The results of an ongoing study in Gottingen, which includes 20 patients so far are described and the potential value of childhood MS for research is stressed. PMID- 1623266 TI - Hereditary disorders including mitochondrial diseases. AB - Correlation between mitochondrial DNA (mtDNA) mutations and biochemical defects associated with several mitochondrial disorders is now possible using cybrid fusions. An understanding of the clinical heterogeneity of many inherited disorders may begin from the observation that different manifestations parallel different mutations in the same gene and, consequently, different activities of the aberrant enzyme in the body. PMID- 1623267 TI - Neuroendocrinology: clinical and experimental. AB - There have been several important publications concerning the aetiology of human pituitary tumours, in particular, delineating some of the gene mutations which may underlie this clinical problem. There have not been any major developments in clinical neuroendocrinology although advances have been made in the pharmacological development of dopaminergic drugs and the diagnosis of Cushing's disease. PMID- 1623268 TI - Alcohol and drug abuse. AB - Neurological complications are well recognized with alcohol abuse, and an increasing amount of literature is emerging describing neurological disease as a complication of other drugs of addiction (recreational drugs). This review covers recent papers related to alcohol and drug abuse. PMID- 1623269 TI - MPTP and other Parkinson-inducing agents. AB - The ability of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to produce parkinsonism has focused attention on potential endogenous or exogenous toxins that may follow similar uptake and conversion pathways to selectively target mitochondrial function in dopaminergic neurones. Exposure to such agents, together with a genetically determined susceptibility, is an attractive working hypothesis for the cause of Parkinson's disease. New insights into the mechanism of action of MPTP and its analogues are presented together with evidence supporting the potential role of endogenously produced toxins in the death of dopaminergic neurones in Parkinson's disease. PMID- 1623271 TI - Movement disorders. PMID- 1623270 TI - Neurotoxins and environmental poisons. AB - Recent applications of modern neurobiological techniques have provided an impetus to understanding mechanisms of neurotoxicity. Environmental chemicals, including aluminium, and the organocompounds of mercury, lead and tin, may trigger neurodegenerative disorders. Regional differences in toxicity may be related to the complexity of the amino acid excitatory systems and the ability of individual cell systems to handle long-term abusive stimulation. PMID- 1623272 TI - Pediatric and developmental neurology. PMID- 1623273 TI - Metabolic disorders and neurotoxicology. PMID- 1623274 TI - It is increasingly difficult for doctors to keep up to date with the growing volume of medical literature. PMID- 1623275 TI - The trouble with spectroscopy papers. AB - Writing a critique and guide for authors of clinical spectroscopy research papers is a likely way of ensuring that one never sees another of one's own papers published in this field. Nevertheless, it is disappointing, though perhaps predictable, that despite its historical foundations in quantitative spectroscopy, the field has its fair share of findings that are not so obviously reconciled. Here is the view of one author, one referee, and one spectroscopy protagonist about what might be expected of a clinical spectroscopy paper. In addition to novelty, the fundamental criteria for acceptance should be that the conclusions are supported by properly and objectively quantified results, and that sufficient experimental detail is provided so that one skilled in the art could reproduce the study and its findings. PMID- 1623276 TI - Dynamic study of the upper airway with ultrafast spoiled GRASS MR imaging. AB - Dynamic magnetic resonance (MR) imaging of the upper airway was not possible previously because of poor temporal resolution. Recently, a rapid technique has been developed that provides the means to obtain multiple images at different section locations with sufficient image quality and temporal resolution to allow a comprehensive, dynamic study of the upper airway. The authors describe an ultrafast spoiled GRASS (gradient-recalled acquisition in the steady state) pulse sequence for dynamic studies of the upper airway. The authors believe that this procedure has potential for identifying and characterizing upper airway abnormalities such as nonfixed occlusions and/or narrowings that may exist in patients with obstructive sleep apnea. PMID- 1623277 TI - Efficacy of nonionic low-osmolar gadodiamide injection in animals with intracranial mass lesions. AB - Gadodiamide injection is a nonionic, low-osmolar formulation of a paramagnetic metal chelate complex consisting of gadodiamide and caldiamide sodium. The efficacy of gadodiamide injection as a magnetic resonance (MR) imaging enhancement medium was evaluated by imaging intracranial 9L-glioma lesions induced in rats and naturally occurring lesions in dogs. T1- and T2-weighted spin echo images were obtained before and after administration of gadodiamide injection at doses of 0.1 and 0.2 mmol/kg. On the precontrast T1-weighted images, the intracranial lesions were not well seen, appearing isointense to normal brain parenchyma. Although the presence of disease was shown unequivocally on the T2 weighted images, the margins of the masses could not be delineated. Postcontrast T1-weighted images were characterized by marked enhancement of the tumor, with no change in signal intensity in the surrounding edematous brain tissue. Gadodiamide injection was efficacious in identifying areas of blood-brain barrier breakdown associated with intracranial masses. PMID- 1623278 TI - OMR, a positive bowel contrast agent for abdominal and pelvic MR imaging: safety and imaging characteristics. AB - To determine the safety and imaging characteristics of OMR--an effervescent solution of ferric ammonium citrate--as a bowel contrast agent, magnetic resonance (MR) imaging at 1.5 T was performed in 29 volunteers. T1- and T2 weighted images of the upper abdomen and pelvis were obtained before and after oral administration of OMR at doses of 100-400 mg of iron in 300-600 mL of water. Respiratory-ordered phase encoding and presaturation pulses were used routinely for artifact suppression. All dose levels of OMR provided marking of the bowel by increasing intraluminal signal intensity; however, the degree and percentage of small bowel opacification appeared more prominent at higher dose levels of iron. Semisolid or watery bowel movements were noted in 31% of subjects, but no clinically important laboratory abnormalities were seen. OMR improved delineation of the head of the pancreas on T1-weighted images in 72% of subjects but was less useful in defining the body and tail. OMR is a safe and effective bowel contrast agent for MR imaging. Because artifacts due to movement of hyperintense bowel may degrade the images, OMR may be most useful on short TR/TE or fast imaging pulse sequences or when combined with antiperistaltic agents. PMID- 1623279 TI - Normal and degenerating articular cartilage: in vitro correlation of MR imaging and histologic findings. AB - Histologic correlation of the different magnetic resonance (MR) appearances of articular cartilage has not been studied extensively. Therefore, the authors correlated thin (high-resolution) MR sections of articular cartilage with histologic sections. Human cadaver lumbar facet joints were imaged with a 1-mm section thickness and a 4-cm field of view, then sectioned and stained for histologic comparison. MR imaging patterns were identified that correlated with normal cartilage and three histologically different patterns of degeneration. PMID- 1623280 TI - Boron-11 imaging with a three-dimensional reconstruction method. AB - A three-dimensional projection reconstruction technique is described for imaging boron-11 distributions, with potential application to boron neutron capture therapy. The method samples a spherical volume of k space uniformly to obtain a 32 x 32 x 32 matrix with voxel size of 0.42 cm3. A signal-to-noise ratio (S/N) of 3 was obtained in 8.5 minutes in a phantom containing 75 micrograms/mL of boron in borocaptate sodium (BSH). Images were obtained in a dog after cessation of an intravenous infusion of BSH and again 30 minutes later, with a maximum boron S/N of about 12. Boron levels in the brain dropped about 6%-8% and were more diffusely distributed on the images obtained 30 minutes after BSH infusion. PMID- 1623281 TI - Reblurred deconvolution method for chemical shift removal in F-19 (PFOB) MR imaging. AB - Perfluorocarbons such as perfluoroctylbromide (PFOB) can be used as contrast agents in the vascular system for fluorine-19 magnetic resonance imaging or as synthetic oxygen carriers. F-19 imaging has been proposed for studying the vascular system, capillary flow, tissue perfusion, and tumor oxygenation. A major difficulty is that F-19 compounds often have complex multipeak spectra. These peaks result in chemical shift artifacts, lower signal-to-noise ratios, and blurred images. Each peak also excites a different section when a section-select gradient is applied. Direct inverse filtering is the simplest deconvolution method for correcting such artifacts; however, two major difficulties present themselves: functional singularity and noise amplification at high frequencies. The use of a new reblurred deconvolution (RED) method appears to overcome these problems. Although this method is based on iterative deconvolution in the spatial domain, the computational overhead is negligible. Since the point spread function and object data are already available in the time domain as FID data, RED appears to be useful for eliminating chemical shift artifacts and suppressing noise amplification while restoring the original image without loss of resolution. PMID- 1623282 TI - MR imaging appearance of intraperitoneal gelatin sponge in mice. AB - Intraperitoneal gelatin sponge can mimic a mass lesion on magnetic resonance (MR) images. To determine the MR imaging characteristics of gelatin sponge over time, a 15 x 10 x 4-mm piece of gelatin sponge soaked in saline was surgically implanted in the peritoneal cavity of 14 mice. Two mice underwent a sham operation. Contiguous axial spin-echo images of the abdomen were obtained with T1 weighted, spin-density, and T2-weighted sequences preoperatively and over a 6 week period postoperatively. Gelatin sponge initially appears as a heterogeneous mass of low signal intensity on T1-weighted images and increasing intensity on spin-density and T2-weighted images, containing multiple round foci of very low signal intensity, attributable to air, at all sequences. Over time, signal intensity further increases and becomes more homogeneous on spin-density and T2 weighted images, although foci of air persist to 3 weeks. By 2-4 weeks, the mass is no longer discrete. Foci of air should help differentiate gelatin sponge from tumor and add gelatin sponge to the differential diagnosis of abscess. PMID- 1623283 TI - Effects related to temperature changes during MR imaging. AB - Magnetic resonance (MR) imaging has been proposed as a method of monitoring the interstitial laser heating of tissue for the clinical treatment of tumors (laser hyperthermia). The treatment causes considerable temperature changes over the time that image data are acquired, and therefore an analysis of the time dependent effects of heating is required. The problem is expressed mathematically, and computer-simulated images are compared with those obtained from experimental heating and imaging of gel phantoms. Results show that at the rates of heating typical for laser hyperthermia and even with the relatively slow standard imaging techniques used, generation of artifact is not a major concern. It is also shown that a spatial spin signal magnitude distribution, evolving in time, is effectively sampled at the time to when the low-numbered phase-encoding steps are collected at to. It is noted, however, that substantial temperature changes during image data acquisition make accurate temperature determination difficult and place limits on MR imaging for quantitative spatial temperature mapping. PMID- 1623284 TI - Quantitative MR signal behavior in cardiac cine loops as a function of heart rate. AB - To evaluate the heart cycle-dependent signal intensity changes in the cardiac chambers, the aorta, and the pulmonary artery, five healthy volunteers were studied with gradient-echo magnetic resonance cine loops at different heart rates. Quantitative evaluation of signal intensity on each side of the cardiac valves showed that there were changes in signal intensity due to section-entry and spin-phase phenomena but none due to the increase in heart rate. The authors conclude that there is no heart rate-dependent signal loss in healthy persons that simulates valvular dysfunction, thus suggesting that signal intensity change can be used as an indicator for this disease, independent of heart rate. PMID- 1623285 TI - Hepatic focal nodular hyperplasia: MR imaging at 1.0 and 1.5 T. AB - Ten cases of hepatic focal nodular hyperplasia (FNH) were studied with magnetic resonance (MR) imaging. Proof of diagnosis was by needle biopsy or follow-up of as long as 5 years. Both short TR/TE and long TR/TE images were obtained. The most common finding was isointensity of the lesion relative to liver parenchyma with all pulse sequences. A central scar was seen in only one patient and was hyperintense on long TR/TE images. Slight hyperintensity of the lesion on short TR/TE and long TR/TE images was seen in two cases. Textural heterogeneity was present in only one of these. The most common presentation in our series was a visually isointense lesion relative to liver on short TR/TE images and an isointense or slightly hyperintense lesion on long TR/TE images. A review of the literature and the present findings suggest that FNH has a variable appearance on MR images. PMID- 1623286 TI - Comparison of MR imaging after barium administration with CT in pelvic disease. AB - The use of magnetic resonance (MR) imaging for evaluating the abdomen and pelvis has been limited by the lack of a suitable contrast agent. The purpose of this study was to compare axial MR imaging after rectal barium administration with computed tomography (CT) for delineation of normal anatomy and lesions of the pelvis. MR images and CT scans of 11 patients were studied retrospectively and independently by four radiologists. No substantial differences in the visualization of normal bowel, iliac vessels, lymph nodes, bladder, prostate, seminal vesicles, uterus, and cervix and in detection of abnormalities were seen between CT scans and axial MR images obtained after barium administration. This preliminary study suggests that axial MR imaging with rectal barium is a useful alternative to CT in evaluating pelvic disease. PMID- 1623287 TI - High-dose gadoteridol in MR imaging of intracranial neoplasms. AB - Twelve patients with a high suspicion of brain metastases by previous clinical or radiologic examinations were studied in a phase III investigation with magnetic resonance (MR) imaging at 1.5 T after a bolus intravenous injection of 0.1 mmol/kg gadoteridol followed at 30 minutes by a second bolus injection of 0.2 mmol/kg gadoteridol. All lesions were best demonstrated (showed greatest enhancement) at the 0.3-mmol/kg (cumulative) dose, with image analysis confirming signal intensity enhancement in the majority of cases after the second gadoteridol injection. More lesions were detected with the 0.3-mmol/kg dose than with the 0.1-mmol/kg dose, and more lesions were detected with the 0.1-mmol/kg dose than on precontrast images. In this limited clinical trial, high-dose gadoteridol injection (0.3-mmol/kg cumulative dose) provided improved lesion detection on MR images specifically in intracranial metastatic disease. PMID- 1623288 TI - MR-guided aspiration cytology in the head and neck at high field strength. AB - Published reports of magnetic resonance (MR)-guided needle biopsy have involved low- and mid-field-strength systems because of the concern of needle artifact and risk of increased needle torque at higher field strengths. To the authors' knowledge, this is the first report of a high-field-strength (1.5-T) system used to guide aspiration cytology in the head and neck in a patient. The procedure was successfully accomplished without additional needle torque or substantial increase in image artifact relative to lower-field-strength imaging. PMID- 1623289 TI - Ionic versus nonionic MR imaging contrast media: operational definitions. AB - An experimental rationale is provided to differentiate between the terms ionic and nonionic for magnetic resonance (MR) imaging contrast media such as gadodiamide and gadopentetate dimeglumine. Four independent types of physical measurements (electric conductivity, osmolality, electrophoresis, and ion exchange) were performed on a range of test compounds, including D-glucose, iohexol, gadopentetate dimeglumine, and gadodiamide. Iohexol, D-glucose, and gadodiamide are shown to be nonionic species at physiologic pH (7.4), not measurably dissociating in solution. A range of gadopentetate salts behave as electrolytes, dissociating into constituent charged ions in aqueous media. Operational definitions for the terms ionic and nonionic are provided, and the terms neutral and net zero charge are compared with nonionic for accuracy. The nomenclature nonionic and ionic is deemed appropriate for differentiating MR imaging contrast media. PMID- 1623290 TI - Temperature monitoring during MR imaging: comparison of fluoroptic and standard thermistors. AB - Temperature readings from standard wire lead thermistor probes and a fluoroptic temperature probe were compared before, during, and after exposure to a spin-echo imaging sequence at 2.35 T. All the probes were placed in saline-filled vials (1 mL capacity) surrounded by dense foam rubber to isolate and preserve local heating effects. There were no consistent differences in the temperatures recorded by the various probes. The authors conclude that wire lead thermistor probes do not exhibit substantial heat deposition when exposed to a standard spin echo imaging sequence at 2.35 T. PMID- 1623291 TI - Dynamic properties of cardiovascular systems. AB - A recently derived mathematical model of an isolated heart is extended here to a closed-loop cardiovascular system. Taking the end-diastolic volume as state variable, the authors show that the closed-loop cardiovascular system can be described by a one-dimensional nonlinear discrete dynamical system that depends on parameters describing the systolic and diastolic properties of the heart, heart rate, total peripheral resistance, and arterial capacitance. Studies of this model show that the system possesses a rich spectrum of dynamical behavior, from stable points through stable cycles to a "chaotic" behavior. It is shown that such an analysis of dynamic behavior yields those domains in the parameter space that correspond to a normal and abnormal beating heart, when the heart ejects time-invariant and time-variant (periodic or aperiodic) stable stroke volumes, respectively. Determination of such domains may lead to better understanding of the specific pathologic mechanism involved in the evolution of an abnormal beating heart. PMID- 1623292 TI - Variance components for discordances. AB - Tests for biotyping isolates give a result that is classified as either positive or negative, indicative of growth or nongrowth of bacteria. The reproducibility of such tests is measured by the number of discordances in replicates of the same measurement. In this analysis the probability distribution of the number of discordances is estimated for each of several tests in the presence of possible random between-laboratory effects as well as random laboratory-test interactions, which are also estimated. PMID- 1623293 TI - Remarks on "persistence in models of three interacting predator-prey populations". AB - For models of three interacting predator-prey populations, a result on the boundedness of solution orbits and a result on ultimate boundedness are presented. A counterexample to another result is also given for comparison. PMID- 1623294 TI - R0 bounds for worst-case endemic mixing models. AB - Upper and lower bounds are presented for the worst endemic prevalence possible in nonrandom mixing models. The bounds require only the value of the reproductive number R0 for the corresponding homogeneous epidemic model. For R0 values of 4 or larger, the difference between the upper and lower bounds on the worst-case prevalence is at most five percentage points. PMID- 1623295 TI - Periodic solutions of population models in a periodically fluctuating environment. AB - A periodically fluctuating environment is assumed in a population-modeling process that generates nonautonomous difference equations. The existence and uniqueness of periodic solutions are studied. A sufficient condition for existence and a necessary condition for uniqueness are obtained. Stability of the periodic solutions is investigated. Several numerical examples are given to illustrate the basic results, and a brief discussion is presented. PMID- 1623296 TI - Decomposition-based qualitative experiment design algorithms for a class of compartmental models. AB - Qualitative experiment design, to determine experimental input/output configurations that provide identifiability for specific parameters of interest, can be extremely difficult if the number of unknown parameters and the number of compartments are relatively large. However, the problem can be considerably simplified if the parameters can be divided into several groups for separate identification and the model can be decomposed into smaller submodels for separate experiment design. Model decomposition-based experiment design algorithms are proposed for a practical class of large-scale compartmental models representative of biosystems characterized by multiple input sources and unidirectional interconnectivity among subsystems. The model parameters are divided into three types, each of which is identified consecutively, in three stages, using simpler submodel experiment designs. Several practical examples are presented. Necessary and sufficient conditions for identifiability using the algorithm are also discussed. PMID- 1623297 TI - The subcritical collapse of predator populations in discrete-time predator-prey models. AB - Many discrete-time predator-prey models possess three equilibria, corresponding to (1) extinction of both species, (2) extinction of the predator and survival of the prey at its carrying capacity, or (3) coexistence of both species. For a variety of such models, the equilibrium corresponding to coexistence may lose stability via a Hopf bifurcation, in which case trajectories approach an invariant circle. Alternatively, the equilibrium may undergo a subcritical flip bifurcation with a concomitant crash in the predator's population. We review a technique for distinguishing between subcritical and supercritical flip bifurcations and provide examples of predator-prey systems with a subcritical flip bifurcation. PMID- 1623298 TI - Compensation and stability in nonlinear matrix models. AB - Stability, bifurcation, and dynamic behavior, investigated here in discrete, nonlinear, age-structured models, can be complex; however, restrictions imposed by compensatory mechanisms can limit the behavioral spectrum of a dynamic system. These limitations in transitional behavior of compensatory models are a focal point of this article. Although there is a tendency for compensatory models to be stable, we demonstrate that stability in compensatory systems does not always occur; for example, equilibria arising through a bifurcation can be initially unstable. Results concerning existence and uniqueness of equilibria, stability of the equilibria, and boundedness of solutions suggest that "compensatory" systems might not be compensatory in the literal sense. PMID- 1623299 TI - 2D-NMR and molecular dynamics analysis of the Torpedo californica acetylcholine receptor alpha 67-76 fragment and of its [Ala76]-analogue. AB - The alpha 67-76 fragment (Trp67-Asn68-Pro69-Ala70-Asp71-Tyr72 -Gly73-Gly74- Ile75 Lys76) of the Torpedo californica acetylcholine receptor (AChR) is selectively recognized by antibodies against the main immunogenic region of the AChR. The antibody binding capacity of its [Ala76]-analogue is usually higher than that of the natural fragment. A conformational analysis of these two decapeptides has been carried out in Me2SO by 2D-NMR and molecular dynamics using the SYBYL and BIOGROMOS programs. The natural sequence presents the most numerous and strongest NOE connectivities and is accordingly less flexible than the [Ala76]-analogue. Due to the flexible orientation of the side chains in both peptides, the NOE backbone side chain and side chain-side chain connectivities have not been introduced as distance constraints in the molecular dynamics calculations. It appeared that the N-terminal heptapeptide in both sequences assumes two very similar folded conformations, whereas the Ala substitution induces conformational flexibility in the C-terminal tripeptide sequence. The most flexible [Ala76] analogue is the most tightly bound to the monoclonal mAb6 anti-AChR antibody, and the transferred NOEs from the bound to the free peptide in D2O reveal some similarity with the intrinsic NOEs for the free natural sequence in Me2SO, suggesting that the bound conformation of the [Ala76]-analogue could not be very different from that of the free natural fragment. PMID- 1623300 TI - Analysis of synthetic peptides using matrix-assisted laser desorption ionization mass spectrometry. AB - Matrix-assisted laser desorption ionization mass spectroscopy (LDI MS), a novel method for analysis of large molecules, has been used for characterization of synthetic peptides and their by-products. The potential of LDI MS is demonstrated by analyzing crude synthetic peptides representing typical members of newly designed peptides and proteins. In the first case, a fragment condensation reaction yielding a highly hydrophobic six-helic bundle template-assembled synthetic protein (TASP) is monitored. Then, a crude 19-mer peptide designed to adopt an amphiphilic alpha-helical structure and its by-products from SPPS are identified. Finally, analysis of crude hirulog-1, a 20-mer peptide designed as a thrombin inhibitor, using C18 reversed phase high performance liquid chromatography (RP HPLC), capillary electrophoresis (CE) and LDI MS, manifests the potential of the latter method. PMID- 1623301 TI - Reduced peptide bond pseudopeptide analogues of neurotensin. AB - Pseudopeptide analogues of the C-terminal hexapeptide of neurotensin (H-Arg-Arg Pro-Tyr-Ile-Leu-OH) were obtained by replacing each peptide bond by the reduced peptide bond CH2NH. The resulting analogues were then examined for their ability to inhibit binding of labeled neurotensin to new-born mouse brain membranes and for stimulation of guinea pig ileum contraction. Replacement of the Ile12-Leu13, Tyr11-Ile12, Pro10-Tyr11 and Lys9-Pro10 peptide bonds resulted in about 2000-, 3400-, 200- and 3400-fold losses, respectively, in binding affinity and 400-, 750 , 250- and 300-fold losses, respectively, in biological activity. Replacement of both Arg8 and Arg9 by lysine led to an analogue exhibiting the same pharmacological profile as the C-terminal hexapeptide of neurotensin. Interestingly, replacement of the Lys8-Lys9 peptide bond by the CH2NH bond produced an analogue exhibiting the same affinity for neurotensin receptors, but 10 times more potent in stimulating guinea pig ileum contraction. N-terminal protected analogues (by the Boc group) showed decreased potency as compared with their amino-free corresponding compounds. PMID- 1623302 TI - Synthesis of neo-glycosylated L-alanyl-D-isoglutamine derivatives as potential immunoadjuvants. AB - The synthesis is described for muramyl-dipeptide-related amphiphilic analogs, where 1,10-diaminodecane served as a lipophilic C-terminal linker for the preparation of a bidentated L-alanyl-D-isoglutamine derivative and incorporation of aldonic and uronic acids at the N-termini as hydrophilic cores. For the N acylation steps via lactones, suitable conditions were elaborated to allow for the use of unprotected or minimally protected aldonic and uronic acid lactones, respectively. These procedures may represent a useful general approach for the synthesis of neoglycopeptides. PMID- 1623304 TI - Synthesis, characterization, and solution conformational analysis of C alpha methyl-, C alpha-benzylglycine [(alpha Me)Phe] model peptides. AB - We have synthesized, by solution methods, and fully characterized a variety of (alpha Me)Phe derivatives and model peptides (to the pentapeptide level). The results of the solution conformational analysis, performed by using infrared absorption and 1H nuclear magnetic resonance, support the view that the (alpha Me)Phe residue is a stronger beta-turn and helix promoter than the unmethylated Phe analog. A comparison is also made with the conclusions extracted from published work on peptides rich in other C alpha-alkylglycyl residues. PMID- 1623303 TI - Solution structure of deltorphin I at 265 K: a quantitative NMR study. AB - Deltorphin I, a delta-selective opioid peptide, has been studied in a DMSOd6/H2O cryoprotective mixture by two-dimensional (2D) NMR spectroscopy in the temperature range 260 K to 305 K. The high viscosity of the solvent at low temperature mimics a distinctive physico-chemical feature of cytoplasm and allows the measurement of a NOESY spectrum rich in intra- and inter-residue effects. Backbone NOEs at 265 K can be calculated with good accuracy in terms of only two limiting conformers: one folded, with a mole fraction of 0.30, and another extended with a mole fraction of 0.70. This calculation is still a rough approximation of the complex conformational equilibria existing in solution but, to the best of our knowledge, is the first one for a flexible peptide, and represents an encouraging starting point for a quantitative evaluation of NMR data of small, flexible peptides in solution. The folded conformer consistent with observed NOEs has a shape surprisingly similar to those of unrelated, rigid, delta-selective opiates. PMID- 1623305 TI - Convergent solid-phase peptide synthesis IX: application to the synthesis of peptides with repetitive sequences. AB - The synthesis of a 36 amino acid peptide containing six conserved repeats of Val His-Leu-Pro-Pro-Pro which corresponds to the glutelin-2 protein of maize has been carried out using a convergent approach. The protected single sequence repeat has been synthesized using a combination of a 9-fluorenylmethyloxycarbonyl (Fmoc) protection scheme and a p-alkoxybenzyl resin. The final peptide, as well as the different intermediate peptides, has been characterized by fast atom bombardment mass spectrometry (FAB-MS) and by co-elution with another sample obtained by stepwise continuous flow synthesis. PMID- 1623306 TI - [Sexually transmittable diseases and the public health service--recommendations for the reorganization of counseling centers for sexually transmittable diseases]. AB - Sexually transmitted diseases (STD), including HIV infection, are a major and increasing health problem in Germany. Primary infection, complications and sequelae of STD are causative for an increasing economic burden. In addition a considerable part of the normal population suffer from persistent refractory virus infections and associated sequelae. The epidemic of both HIV and other STD and iv-drug abuse are closely related. The Public Health strategy in Germany is regulated by an outdated legislation to fight venereal diseases (Gesetz zur Bekampfung der Geschlechtskrankheiten, July 1953) and traditionally consisted in screening tests for bacterial STD in female prostitutes and in case-finding produres. Results of recent epidemiological, social and behavioural research urgently suggest a new approach for STD programmes on the lines of recommendations by the World Health Organization. PMID- 1623307 TI - [Prevalence of asthma in 6,000 10-year-old children in Munich and Upper Bavaria based on physicians' diagnoses and a symptom score]. AB - In the Munich Survey on Asthma and Allergy the parents of 9,349 fourth-class schoolchildren (mean age 9.8 years) in Munich and Southern Bavaria were addressed by a questionnaire to which 8,204 responded (87%). In 7,192 children (76%) a skin prick test was performed and 7,284 (77%) had pulmonary function tests with maximum expiratory flow-volume loops before and after cold air challenge. Of the 6,083 children of German nationality, 160 children (2.6%) had physician-diagnosed asthma, 79 (1.3%) so called asthmoid bronchitis and 373 children (6.1%) spastic bronchitis. Since physician-diagnosed diseases does not reflect all children with respiratory disease, symptoms reported in the questionnaire, results of skin prick and pulmonary function tests were combined to a score of probable asthma (VSA) with 9 items. Of the group with physician-diagnosed asthma, 79.4% of the children (127) have an elevated VSA, of 68.4% (54) of asthmoid bronchitis, 35.9% (134) of spastic bronchitis, 11.4% (192) of simple bronchitis and 3% of (114) never-diagnosed bronchial disease. The cumulative prevalence of asthma in ten year-old children is therefore estimated at 10.2%. Only half of these children have been diagnosed with asthmatic disease. PMID- 1623308 TI - [Acceptance of social security by the German population]. AB - Against the background of persistent problems of financing and monitoring the system of social security as practised in the Federal Republic of Germany, empirical research into preferences and acceptance has gained increasing importance. The acceptance of social security by the population has been checked empirically by means of data of the Socio-Economic Panel. The following questions have been studied: Which degree of acceptance applies generally speaking to the existing system? Are there differences in respect of acceptance regarding the various subdivisions of social insurance and how are they to be explained? What are the conclusions that can be arrived on the basis of these results? Overall assessment of the indicators employed shows that on the whole a high degree of acceptance is accorded to the existing security system. It cannot be concluded from the results that a fundamental reorganisation of the entire system towards security mainly on the individual's own responsibility would be in accordance with the preferences of the great majority of the population. Reorganisation would have to reckon with a low acceptance level. However, the monthly contributions--especially in respect of sickness insurance--are considered to be too high by part of the population. PMID- 1623309 TI - [Recent psychiatric classification systems and their significance for forensic psychiatry]. AB - The influence of operationalized diagnostic systems is growing steadily in general and forensic psychiatry. This article discusses the historical context and the advantages and problems that may occur in the application of the new diagnostic systems. It is of special importance that the improvement of communication and reliability within psychiatry does not lead to an uncritical or even dogmatical understanding of the new diagnostic categories. PMID- 1623310 TI - [Summary of important results of the Kasseler Symposium 28/29 June 1991 on the current status of endoscopic surgery. 34th symposium in Kassel--endoscopic surgery--progress or method? A critical evaluation of its status]. PMID- 1623311 TI - [Comments on the development of a new public health regulation for the Mecklenburg-Vorpommern district]. PMID- 1623312 TI - Subgroups in autism: are there behavioural phenotypes typical of underlying medical conditions? AB - Fifty-nine cases with infantile autism/autistic disorder were subclassified according to associated medical condition (fragile-X, tuberous sclerosis, neurofibromatosis, hypo-melanosis of Ito, Moebius syndrome, Rett syndrome, and a 'new' syndrome associated with a marker chromosome). It was concluded that, even within a group of cases fitting currently accepted criteria for autism, there is considerable variation in symptom profile depending on the exact type of associated medical condition. PMID- 1623313 TI - Properties of perception of laterally moving objects in persons with profound retardation. AB - Twenty-two persons with profound retardation were assessed for their perception of moving objects at a velocity of 5 degrees s-1. Abnormalities were not found in the ocular structures and optic discs of subjects upon ophthalmological examination. Stimuli consisted of six habituation trials and two test trials. Duration of eye movement in pursuit of stimulus was estimated by calculating the linearity and gradients of electro-oculograms. Subjects were divided into three groups based on the change of estimated time of pursuit eye movement. Those showing habituation as well as dishabituation (group 1) had higher developmental communicative ages than subjects with only habituation (group 2) and subjects who did not exhibit habituation (group 3). The results indicated a relationship between the perception of moving objects and the development of communication level in persons with profound retardation. The present study investigated abnormalities in the computer tomographic scanning of the subjects' heads and found cerebral disturbance of the visual cognition of moving objects in persons with profound retardation. PMID- 1623315 TI - The test-retest reliability and stability of the WAIS-R in a sample of mentally retarded adults. AB - Fifty mentally retarded adults were administered the Wechsler Adult Intelligence Scale-Revised (WAIS-R) on two separate occasions, with the mean amount of time between testings being 2 years, 8 months. The data were examined in an effort to study the test-retest reliability and stability of the WAIS-R with the mentally retarded. Based on correlational, t-value and percentage of scale score change information, the authors concluded that the WAIS-R IQs appeared to possess good test-retest reliability and stability over an approximate 2.5 year period for the present sample of mentally retarded adults. PMID- 1623314 TI - Violence, death and associated factors on a mental handicap ward. AB - The characteristics of all the patients admitted to a high-dependency mental handicap ward over a 21-month period were examined. The patients that had been responsible for acts of violence on the ward were compared with those who had not. Violent patients were significantly younger and more likely to have an abnormal electroencephalogram. Meningoencephalitis as the aetiology of mental handicap was over-represented in the violent group. The level of violence was alarmingly high with 620 violent incidents over 21 months (30 per month). Four patients accounted for 74% of the violence and two of these four patients suffered sudden, unexpected deaths. The relationship between violence and sudden death is examined, and the implications of pharmacological intervention with anticonvulsants for violent patients with abnormal electroencephalogram results are discussed. PMID- 1623316 TI - Severe behaviour problems associated with rapid cycling bipolar disorder in two adults with profound mental retardation. AB - The authors report the clinical histories of two adults with profound mental retardation, features of rapid cycling bipolar disorder, and periodic maladaptive behaviour. In each case, primary features of mania and depression were identified, operationally defined and measured with an ongoing data system, which was used to track SIB and aggression. In the first case, data analysis across days showed that 1-week episodes of depressive features alternated with 2-week episodes of manic features and that SIB was only associated with the depressive features. In the second case, episodes of manic and depressive features alternated every few days, and aggression was only associated with the manic features. These cases suggest that severe behaviour problems can be a state dependent phenomenon of bipolar disorder. The behaviour monitoring system provided an objective methodology for aiding in the diagnosis of bipolar disorder with profoundly handicapped adults. PMID- 1623317 TI - [Current aspects of preoperative autologous blood donation with legal implications]. PMID- 1623318 TI - [Erythropoiesis and iron metabolism in autologous blood donation]. AB - Autologous blood donation before elective surgery has been widely endorsed as good transfusion practice. Although only 6 percent of patients undergoing elective orthopedic surgery are unable to donate 3 autologous units, 40 percent cannot donate 4 units because they become anemic [1,2]. According to the results of our study this must be due to different problems in bone marrow dynamics, which cannot be overcome by unselected use of human recombinant erythropoietin alone [3]. PMID- 1623319 TI - Comparison of plateletpheresis using Cobe Spectra System and Fresenius AS 104. AB - To evaluate separation efficiency and concentrate purity, each of 50 donors underwent platelet (PLT) collection on both the Cobe Spectra and Fresenius AS 104 with the constancy of processed blood volume, ACD/blood ratio 1:10 and a blood flow of 50 ml/min. For the Fresenius AS 104 two protocols - V 4.11 and V 4.4 - were evaluated. Both systems provided high quality PLT collection: PLT yield 3.91 +/- 0.74 x 10(11) (Cobe); 4.16 +/- 1.12 x 10(11) (V 4.11); 4.66 +/- 0.89 x 10(11) (V 4.4). The mean cell contamination was low with all procedures, resulting in less WBC contamination with the Fresenius AS 104, whereby the higher efficiency obtained by the protocol version V 4.4 correlated with an increased of WBC contamination. PMID- 1623320 TI - [Importance of the interface position in thrombocytapheresis with the AS 104 cell separator]. AB - In plateletpheresis with the Fresenius AS 104 the interface position influences the separation efficiency and the cell contamination of the platelet concentrate. The aim of the present study is to improve the purity of the platelet concentrate by changing the interface position. Increasing interface position results in rising separation efficiency and cell contamination. Alternating interface position gives the best result with significantly lower leukocyte contamination and only a slight decrease of separation efficiency. Nevertheless we prefer separations with variable interface position to reduce an immunisation of the recipient by white blood cells. PMID- 1623321 TI - Teflon bags for 5-day storage of platelet concentrates (PC) from cell separator. AB - There exist no data yet about platelet storage in teflon bags. Therefore, a paired study has been performed to evaluate their suitability for the 5 days storage of platelet concentrates (PC) from the cell separator Fresenius AS-104. The PC's of the AS-104 were stored in teflon as well as in polyolefin bags each (PL-732). In addition, PC's of the Baxter CS-3000 were stored in PL-732. PH, cell counts, platelet morphology, aggregation, adherence and ADP/ATP concentration, plasma beta TG, glucose, lactate and thrombin-antithrombin III complexes were investigated at day 0, 3 and 5 of storage. The results show that the teflon bags are quite suitable for 5 day storage of the PC's. But the functional superiority of fresh PC's from the AS-104 seemed to be reduced by storage in teflon bags compared to storage in PL-732. The unfavorable size and geometry of the teflon bags used could have been the cause. Therefore, size and geometry were consequently changed in the meantime. PMID- 1623322 TI - Leukocytapheresis: evaluation of a new procedure for the blood cell separator Fresenius AS 104. AB - For granulocyte separation from peripheral blood with the Fresenius blood cell separator AS 104 a new procedure and a new tubing set were developed and evaluated. Separation is done in cycles of 400 ml of whole blood processed, with continuous blood flow of 50-55 ml/min, speed 750 rpm. HES-450 is added for sedimentation acceleration together with citrate, ratio 1:10. At the end of each cycle granulocytes were pumped out of the separation chamber into the collection container. After processing 13 cycles of 400 ml whole blood/HES-citrate-volume a total yield of 9.20 +/- 2.80 x 10(9) white cells were collected in volumes of 125 ml. 47 +/- 9% of the leukocytes collected were granulocytes, this corresponds to collection of 1.05 +/- 0.09 x 10(9) granulocytes per liter of processed blood. The efficacy of granulocyte collection is 22.5 +/- 5.6%, viability is more than 95%. With this procedure it is possible to collect granulocytes with the blood cell separator Fresenius AS 104 in therapeutical doses. PMID- 1623324 TI - Virus inactivated single-donor fresh plasma preparations. AB - Photodynamic virus inactivation of single units of human fresh plasma in their plastic containers can be achieved by illuminating the plasma with visible light in the presence of low concentrations of one of the phenothiazine dyes methylene blue or toluidine blue. This procedure abrogates the infectivity of numerous lipid-enveloped viruses including that of human immune deficiency virus-1. In contrast, the functional activities and immunological properties of plasma proteins are only moderately influenced. Animal studies and the first clinical data suggest that photodynamically virus inactivated fresh plasma is as well tolerated as conventional fresh frozen plasma. PMID- 1623323 TI - [Experiences with a simple microtiter plate technique for GPT screening of blood donors]. AB - A simple microtiterplate method to screen blood-donors for elevated alanine transaminase (ALT) was developed. The method permits a sufficiently precise measuring at room temperature without temperature control and has a high performance. The method was validated by comparison with a standardized method. PMID- 1623325 TI - [Initial experiences with methylene blue virus inactivated fresh frozen plasma: results of a clinical and in vitro study]. AB - Methylene blue (MB) has recently been introduced to inactivate viruses in single donor fresh frozen plasma (FFP) units. In the first clinical study 519 units of MB-treated FFP were given to 103 patients. No specific clinical side effects with adverse reactions were recorded. However, after thawing, clots were observed in 9 of the first 110 units, although the medical staff had thawed the MB-FFP in exactly the same manner as the conventional FFP in which clots are extremely rare. The possible effects of methylene blue were investigated by subsequent in vitro experiments: Methylene blue together with light led to generation of fibrin(ogen) derivatives which have an increased tendency for aggregation but cannot be normally clotted by thrombin and even seem to interfere with normal fibrin polymerization. Inadequate conditions during plasma preparation such as long illumination or temperatures above 40 degrees C enhanced the generation of these fibrin(ogen)-derivatives. In addition, special requirements for producers and users of MB-FFP and further investigations are necessary in order to prevent complications. PMID- 1623326 TI - A pasteurized therapeutic plasma. AB - A process to subject pooled human plasma to a viral inactivation treatment by heating in the liquid state for 10 hrs at 60 degrees C (pasteurization) has been designed and evaluated. Activity recovered from clotting factors and protease inhibitors exceeded 80%. Overall clotting activity remained good. No activation of coagulation factors was detected. The process did not generate aggregates. No side effects (toxicity, hypotension, variation in heart rate, thrombogenicity) could be detected in animal models. Virus kill studies, using 7 lipid-enveloped and non-enveloped viruses including HIV-1 and Sindbis virus, revealed inactivation levels similar to those obtained for plasma derivatives. Thus, pasteurisation of human plasma can be achieved in conditions that allow good recovery of biological properties while ensuring a high degree of inactivation of lipid-enveloped and non-enveloped viruses. PMID- 1623327 TI - Autocrine inhibition of parathyroid cell secretion requires proteolytic processing of chromogranin A. AB - Chromogranin A (CgA, Secretory Protein-I) is a protein of about 450 amino acids representing a major soluble component of the secretory granules of parathyroid and other endocrine and neuroendocrine cells. In the parathyroid, CgA is costored and cosecreted with parathormone (PTH). We earlier found that CgA and the derived peptide, pancreastatin, inhibited secretion of PTH and CgA by parathyroid cells in culture and that CgA antiserum stimulated secretion above the maximum achieved at low (0.5 mM) Ca2+. In the present study, porcine parathyroid cells were incubated at different cell concentrations at low Ca2+. The amount of secreted CgA increased over the 6-h incubation period at 1 x 10(6) to 4 x 10(6) cells/ml, but plateaued after 3 h at 6 x 10(6) cells/ml. Secretion did not plateau when antisera were added at 3 h. Conditioned medium contained a factor or factors that blocked secretion by fresh parathyroid cells at 0.5 mM Ca2+. Pulse-chase studies revealed that 40% of the secreted CgA was processed after 6 h of chase. alpha-2 macroglobulin, an inhibitor of proteolytic processing, increased the amount of CgA in the medium by 30% at 1 h of chase and decreased the amount processed to 20% by 6 h. Other protease inhibitors similarly enhanced the amount of CgA in the medium. These data indicate that proteolytic processing of intact CgA is requisite for its autocrine inhibitory activity. PMID- 1623328 TI - Pancreastatin and bovine parathyroid cell secretion. AB - Chromogranin A (CgA) is an acidic glycoprotein found in secretory granules of multiple peptidergic tissues and cosecreted with the resident peptide hormones. Pancreastatin is an amidated, biologically active peptide whose sequence is contained within CgA. We investigated the effect of the C-terminal fragment of bovine pancreastatin (bP32-47) on bovine parathyroid cell secretion. bP32-47 amide inhibited low-calcium-stimulated PTH secretion by 44% and chromogranin A (CgA) secretion by 33%. We were able to identify a pancreastatin-like peptide as a very minor component of the endogenous breakdown peptides from CgA. However, using several approaches, we were unable to detect pancreastatin in secretory granule extracts or in incubation media. We conclude that although exogenous bovine pancreastatin has inhibitory effects on secretion, detectable pancreastatin is not secreted under normal incubation conditions. Based on our current data, we would question the physiologic importance of pancreastatin in bovine parathyroid glands. PMID- 1623330 TI - Bone remodelling does not decline after menopause in vertebral fracture osteoporosis. AB - There is considerable current interest in whether activators of bone remodelling, such as IL-1 and other cytokines, are involved in the pathogenesis of osteoporosis. We have therefore studied indices relating to remodelling activation in 50 patients with postmenopausal vertebral osteoporosis and 12 with hip fracture osteoporosis in comparison with 25 age- and sex-matched controls. Because of uncertainty regarding the accuracy of current biochemical markers of bone formation with respect to the estimation of whole body rates of bone formation, a 85Sr-based radioisotopic method was used. This method was previously validated by comparison with data obtained after double in vivo labelling of transiliac biopsies taken nearly simultaneously. Bone resorption was estimated from urinary hydroxyproline data. Controls selected for their continued good health showed a progressive and statistically highly significant decline in indices of bone formation with time after menopause. No such decline was seen in the vertebral fracture patients (P less than 0.005). There were no hip fracture patients within 10 years of menopause so this statistical test could not be applied appropriately to them. The hydroxyproline data were consistent with the suggestion arising from the bone formation data that remodelling declines progressively after menopause in the controls but not in the vertebral fracture patients. The data also suggested that these two fracture groups were in more negative calcium balance than the controls, this being particularly marked in the hip fracture cases. Plasma osteocalcin data correlated moderately well with the kinetic measurements of bone formation. It is concluded that vertebral fracture osteoporosis is associated with prolongation of menopausal levels of bone remodelling which is inappropriate by comparison with healthy controls. PMID- 1623329 TI - A simple method to assess osteoclast-mediated bone resorption using unfractionated bone cells. AB - To determine osteoclastic bone resorption we established a simple assay system in which unfractionated cells obtained from femora of 13-day-old mice were cultured on a dentine slice and the number of osteoclasts and their induced pit area on the slices were measured. When the bone cells (1 x 10(5) cells/dentine slice) were cultured in the presence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or human parathyroid hormone (hPTH) for 4 days, at which time newly-formed osteoclasts were not detected, the pit area was dose-dependently increased, being a 4.3- or 4.1-fold respective increase over the control at a 10(-8) M concentration of hormones. Chick calcitonin (cCT) inhibited the osteoclastic bone resorption induced by either of these hormones. cCT alone also suppressed the bone resorption by the cells (3 x 10(5) cells/dentine slice). These findings indicate that 1,25(OH)2D3 or hPTH may mainly activate pre-existing osteoclasts, resulting in increased bone resorption, and that cCT may suppress this osteoclastic activity. When 1,25(OH)2D3 or hPTH was added to the cells pre-cultured in factor free medium for 6 days, at which time pre-existing osteoclasts had almost degenerated, new osteoclasts were formed, resulting in an increase in pit formation. Thus this system is a useful method which could more sensitively evaluate the effects of hormones or factors on osteoclast formation and activation than other previous systems. PMID- 1623331 TI - Biochemical assessment of bone loss in patients on long-term thyroid hormone treatment. AB - To test conditions under which thyroid hormone might be deleterious to bone, we studied a group of 58 patients who had undergone thyroidectomy because of thyroid cancer 1 to 21 years previously and were treated with steady doses of exogenous thyroid hormone. Vertebral bone density (BMD Z-score) was significantly reduced and biochemical indices of bone resorption (urinary hydroxyproline and plasma tartrate-resistant acid phosphatase activity) and of osteoblastic activity (plasma osteocalcin and bone isoenzyme of serum alkaline phosphatase) as well as the calculated prevalence of bone resorption relative to osteoblastic activity (HBP) were significantly increased in thyroid hormone-treated post-menopausal women but not in men and premenopausal women. The HBP as well as the biochemical indices of bone remodeling were significantly negatively correlated with serum TSH levels. In treated patients, BMD Z-score was significantly dependent on the HBP, menopausal state, duration of treatment and serum TSH levels. In conclusion, the further increase in bone resorption by thyroid hormone is predisposed by menopausal changes in bone turnover. The simultaneous evaluation of biochemical indices of bone resorption and formation improves the assessment of bone loss in patients treated with thyroid hormone in a suppressive dose. PMID- 1623332 TI - Evaluation of vitamin D-binding protein and vitamin D metabolite loss in children on continuous ambulatory peritoneal dialysis. AB - We measured the serum concentration of vitamin D-binding protein (DBP) in children with chronic renal failure (CRF). We also evaluated the relationships between the peritoneal loss of vitamin D metabolites, DBP and albumin in nine children on continuous ambulatory peritoneal dialysis (CAPD). The serum levels of DBP in children with CRF were significantly higher than in normal children. The mean serum DBP level in CRF children undergoing CAPD was slightly lower than in CRF patients who were not on dialysis. In patients on CAPD, the peritoneal loss of 25-hydroxyvitamin D (25OHD) showed a significant positive correlation with the DBP concentration in the dialysate (r = 0.855, P less than 0.005). In contrast, the peritoneal loss of 1,25-dihydroxyvitamin D (1,25(OH)2D) showed a significant correlation with the loss of albumin in the dialysate (r = 0.779, P less than 0.01). The synthesis of 1,25(OH)2D3 is reduced in advanced renal failure, and the peritoneal losses of the active vitamin D sterols in patients on CAPD may aggravate this deficiency. We recommend that supplementation of active form of vitamin D, such as 1 alpha-hydroxyvitamin D3 or 1,25(OH)2D3, is important in CAPD patients, particularly those with elevated peritoneal loss of DBP and/or albumin. PMID- 1623334 TI - Dietary calcium as a statistical determinant of spinal trabecular bone density in amenorrhoeic and oestrogen-replete athletes. AB - A study investigating the relationship between spinal trabecular bone density (measured by QCT), dietary calcium (measured by questionnaire) and menstrual status in 67 elite female athletes was undertaken. Twenty-five athletes were amenorrhoeic, 27 eumenorrhoeic and 15 were taking an oral contraceptive. The mean bone density was significantly lower (P less than 0.0001) in the amenorrhoeics (168 mg/cm3; 95% confidence interval 154-182) than in the eumenorrhoeics (211 mg/cm3; 197-224) and oral contraceptive takers (215 mg/cm3; 197-233). There was also a significant positive linear correlation between trabecular bone density. However, factors with which calcium intake may be linked, such as energy intake and expenditure, were not measured and therefore it is possible that this relationship is indirect. Further studies on the relationship between dietary calcium and bone mineral density in young women are needed. PMID- 1623333 TI - Bone hypertrophy and trabecular generation in Paget's disease and in fluoride treated osteoporosis. AB - The replacement of lost trabeculae characteristic of postmenopausal osteoporosis is problematic, since a biological pathway has not been established for trabecular regeneration de novo in the healthy, intact, mature skeleton. Possible pathways for trabecular replacement may occur under pathological conditions, in particular those associated with bone hypertrophy. The topography of trabecular hypertrophy was compared in two groups of subjects with disease- or treatment induced osteosclerosis following a period of atrophy. In Paget's disease and fluoride-treated osteoporosis a thickening of rarefied trabeculae in both was associated in Paget's disease only with an increase in the trabecular number and the transformation of a discontinuous arrangement into a more continuous network. The sequence seems to be a progression of intratrabecular resorption normally attendant upon a period of trabecular thickening. The failure of fluoride-treated bone in this respect, due to the unusual stability of the fluorotic skeleton, may provide insight to more effective anabolic regimens. PMID- 1623335 TI - Selected bibliography. PMID- 1623336 TI - Junior doctors on the warpath. PMID- 1623337 TI - Cognitive-behavioral approaches to panic disorder and social phobia. AB - In the past several years, substantial progress has been made in developing relatively efficient and seemingly effective brief psychosocial treatments for anxiety disorders. Knowledge has advanced along both biological and psychological fronts, although the greater effort has been put into understanding the neurobiological basis of anxiety disorders and developing appropriate, effective pharmacological treatment. Nevertheless, psychological knowledge has also advanced, and a more recent trend is to integrate psychological and biological advances at the level of psychopathology and treatment. The author highlights recent developments in understanding the psychological basis of two anxiety disorders: panic disorder and social phobia. He then describes psychosocial treatment protocols for these disorders that have been developed at the Center for Stress and Anxiety Disorders at the State University of New York at Albany, and reviews data on their effectiveness. PMID- 1623339 TI - Psychodynamics of panic disorder and social phobia. AB - d psychological treatments of psychiatric disorders are often wrongly polarized. The related anxiety disorders, panic disorder and social phobia, illustrate the interdependence of biology and psychology. The author describes current psychodynamic understanding of the factors that contribute to the etiology and pathogenesis of these disorders. He concludes by stressing the value of integrated, psychodynamic treatment. PMID- 1623338 TI - Psychopharmacological treatment of panic disorder. AB - Panic disorder is a serious, often chronic condition that warrants vigorous treatment. The benzodiazepines, particularly the high-potency compounds alprazolam and clonazepam, provide prompt relief, often with few side effects. Tricyclic antidepressants and monoamine oxidase inhibitors are also effective, although patient acceptance may be limited by a slower response and side effects that mimic some symptoms of panic attacks. The author suggests strategies for the most effective use of these agents. PMID- 1623340 TI - Evaluation and management of the treatment-resistant anxiety disorder patient. AB - Effective evaluation and management of patients with anxiety disorders require an integrated theoretical model that predicts risk for the disorder as a consequence of constitutional vulnerability shaped by developmental experience and activated or influenced by environmental factors. From this perspective, the author describes a rational therapeutic strategy with treatment-resistant patients. He particularly urges a careful evaluation of risk factors and associated conditions that may contribute to persisting distress. PMID- 1623342 TI - Subungual melanoma: a clinico-pathological study of 24 cases. AB - Twenty-four patients with subungual melanoma (13 women and 11 men) had a mean age of 61.6 years. Twenty-two lesions arose either on the thumb or hallux. The mean delay before diagnosis was 30 months. Two patients presented with stage two melanoma and three of the melanomas were in situ lesions (Clark level 1). Nineteen melanomas were Clark level 4 or 5 and the mean thickness of the invasive melanomas was 4.7 mm. Seven patients died of metastatic disease (mean survival 10 months, range 6-50 months). Clark level, thickness and mitotic activity of the melanomas correlated with poor clinical outcome. Delay in presentation and the presence of advanced disease contribute to the poor prognosis of this tumour. PMID- 1623341 TI - Integrated treatment of panic disorder and social phobia. AB - The integrated treatment of disabling anxiety disorders such as panic disorder and social phobia draws on an understanding of psychodynamic theory, cognitive behavioral theory, and psychopharmacology. Regardless of the treatment employed, clinicians are encouraged to focus on interrelated factors affecting the course of the illness and its treatment, including differential diagnosis, etiology, patient education, symptomatic relief, underlying causes, and therapist anxiety. The author delineates eight key principles that foster the optimal choice or combination of treatment methods, and gives a case example to illustrate how these principles apply. PMID- 1623343 TI - Delay between expansion and expander/implant exchange in breast reconstruction--a prospective study. AB - It has been suggested that delay between expansion and insertion of the definitive prosthesis in breast reconstruction reduces the incidence of adverse capsular contracture. We have carried out a prospective trial to examine this hypothesis. 65 patients were randomly allocated into two groups; in one, insertion of the definitive prosthesis was 2 weeks following expansion ("immediate") and in the other, 6 months ("delayed"). The incidence of adverse capsular contracture assessed both by the Baker Scale and a linear analogue scale showed no difference between the two groups. A new objective method for measuring ptosis using a specially designed template is described. The degree of ptosis was not affected by the delay. PMID- 1623344 TI - The distally based posterior tibial arterial adipofascial flap. AB - A distally based posterior tibial artery adipofascial flap with skin graft was used for the reconstruction of soft tissue defects over the Achilles tendon in three cases and over the heel in three cases. Good resurfacing with protective sensation of these wounds was achieved. There was no breakdown of the graft or morbidity of donor sites, which were closed primarily. We believe there were many advantages to this adipofascial flap and that it is an ideal choice for the reconstruction of soft tissue defects in the lower third of the leg and foot, especially over the Achilles tendon. PMID- 1623345 TI - The V.L.S. classification for secondary deformities in the unilateral cleft lip. AB - A classification designed to be used as a simple and reproducible method to evaluate the residual lip deformities following unilateral cleft lip repair is presented. It was developed by analysing the appearance of the upper lips of 81 patients referred to the author with repaired unilateral clefts. The assessment of each lip was divided into 3 separate components: the vermilion (V), the lip itself (L), and the scar (S), and the resulting classification was termed the V.L.S. classification. PMID- 1623346 TI - The V.L.S. classification for secondary deformities in the unilateral cleft lip: clinical application. AB - Results obtained in 70 cleft lip and palate patients who were assessed using the V.L.S. classification are presented. Of these 70 patients, 24 (34%) had had a Millard repair, 13 (19%) a straight line repair, and 33 (47%) had had a repair incorporating a Z-plasty. Both the Millard repair and the Z-plasty repair were associated with a lip of equal height in 54% of patients, whilst in the straight line repair group, 69% of patients had lips of equal height. A long lip was more often associated with the Z-plasty type repair group (27%) of patients, and short lips were more associated with Millard type repair (33%), and straight line repair (31%). Irrespective of the technique used, a notch at the site of the scar was the most common defect found at the vermilion. Wideness and irregularity were the most common unaesthetic features of the scar. PMID- 1623347 TI - Idiopathic muscular torticollis in children: the Cape Town experience. AB - 54 cases of Idiopathic Muscular Torticollis (IMT) referred for surgery over a 23 year period and 134 cases referred for physiotherapy over a 5-year period have been reviewed. Long-term cosmetic and functional results for 30% of the surgical cases are presented, with a mean follow-up time of 10.5 years. Demographic features, the role of physiotherapy, the timing of surgery and serial assessment are discussed and results are compared with similar studies from other centres. Locally, of the 134 cases referred primarily for physiotherapy, 36% defaulted from treatment, 60% enjoyed lasting benefit and 4% required subsequent surgical intervention. In the surgical cases, while early surgery appears preferable, delayed operation, even up to the ages of 4 or 5 years did not seem to prejudice long-term results, providing that the advent of facial hemihypoplasia did not precede surgery. Delay beyond this point, or roughly 6 or 7 years of age, would seem to prejudice function and/or cosmesis. PMID- 1623348 TI - Are rhinoplasty patients potentially mad? AB - Rhinoplasty patients have long been considered to be psychologically unstable and therefore a "risky" group upon which to operate. Patients who had rhinoplastic operations more than 5 years ago were contacted by post and their psychological health assessed by the use of psychometric tests. The results show no evidence to support earlier suggestions that requests for rhinoplasty may be early symptoms of severe psychiatric disease. However, several points do emerge. Male patients show more symptoms of anxiety and depression than normal, and female patients who give no history of injury preceding their operation behave in a more extrovert and sociable manner than normal. Furthermore, patients of both sexes who give no history of injury before their operation, even though pleased with the operative results, are more self-conscious of their appearance than those who were injured prior to their rhinoplasty. PMID- 1623350 TI - The radial forearm--flexor carpi radialis myocutaneous flap: case report. AB - A patient sustained a compound fracture of the elbow resulting in a deep soft tissue defect with exposed bone, joint and nerve. The flexor carpi radialis (FCR) muscle was incorporated within the radial forearm island flap to cover the defect. Wrist flexion was not compromised by this procedure. The blood supply and applications of the radial forearm--flexor carpi radialis myocutaneous flap are described. PMID- 1623349 TI - Xeroderma pigmentosum: resurfacing versus dermabrasion. AB - Three patients of Xeroderma Pigmentosum (XP) have been managed for recurrent tumours. Improvement in pigment pattern was observed at both the donor as well as the recipient sites. An attempt has been made to prevent further occurrence of tumours over the exposed parts of the body by resurfacing and also by dermabrasion. A comparative study of the two procedures is being carried out and the preliminary results are discussed. Deep dermabrasion appears to be preferable as a prophylactic procedure. PMID- 1623352 TI - 'Angiosome theory'. PMID- 1623351 TI - Posterior pharyngeal tattooing: localising the implant in velopharyngeal incompetence. AB - A technique of preoperative localisation of pharyngeal wall implants for velopharyngeal incompetence is described. The nasal approach in the non-sedated patient permits precise and permanent posterior pharyngeal wall tattooing for accurate implant location. PMID- 1623353 TI - Breast implant seroma in pregnancy. PMID- 1623354 TI - Landing patterns in netball: analysis of an international game. AB - The passing and landing patterns among netball players were investigated by examining all the 595 passes in an international match between Australia and New Zealand. Intra-class correlations were used to test inter-observer reliability. The independence of two variables was tested using a Pearson chi 2 test and a contingency coefficient was used to assess the degree of association between variables. An inter-rater reliability in the identification of movement patterns was 0.99. Most of the landings observed in this match were on the forefoot and not the hindfoot as generally reported in controlled experiments. Only 14% of the players leapt to receive a pass compared with 76% reported earlier under controlled environments. The distribution of passing techniques unexpectedly showed that approximately 50% of all the players did not reach for the ball as it was thrown directly to them. However, over 70% of the players threw straight passes which were mainly received in the chest quadrant and other types of passes such as loop, bounce and rebound were used less frequently. Nearly 50% of all players used a right-handed pass to dispose of the ball, while the next most popular pass was to use both hands (40.2%). Landing and passing patterns differed between players in different positions. Footfall patterns on landing after a catch were associated with the trajectory of the ball. PMID- 1623355 TI - Making weight: a case study of two elite wrestlers. AB - Two mature elite Sambo wrestlers were studied during a 22-day pre-European Championship period, during which they were to lose weight and maintain their top physical performance characteristics. During this time the athletes underwent intensive training coupled with a hypocaloric diet. Both lost approximately 8% of their initial body weight, while maintaining their pre-weight loss maximum oxygen uptake, anaerobic threshold and maximum isometric strength. These variables therefore increased when expressed relative to the lower body weight. Isometric endurance and short-term sprinting ability, however, were compromised by the weight-loss regimen, decreasing by up to 7% and 13% respectively. Following a well-planned weight-reduction programme coupled with serious training, aerobic power and isometric strength were unaffected and/or improved, but prolonged anaerobic exercise performance was impaired. PMID- 1623356 TI - Effect of caffeinated coffee on running speed, respiratory factors, blood lactate and perceived exertion during 1500-m treadmill running. AB - Using a motorized treadmill the study investigated the effects of the ingestion of 3 g of caffeinated coffee on: the time taken to run 1500 m; the selected speed with which athletes completed a 1-min 'finishing burst' at the end of a high intensity run; and respiratory factors, perceived exertion and blood lactate levels during a high intensity 1500-m run. In all testing protocols decaffeinated coffee (3 g) was used as a placebo and a double-blind experimental design was used throughout. The participants in the study were middle distance athletes of club, county and national standard. The results showed that ingestion of caffeinated coffee: decreases the time taken to run 1500 m (P less than 0.005); increases the speed of the 'finishing burst' (P less than 0.005); and increases VO2 during the high-intensity 1500-m run (P less than 0.025). The study concluded that under these laboratory conditions, the ingestion of caffeinated coffee could enhance the performance of sustained high-intensity exercise. PMID- 1623357 TI - Accuracy of Borg's ratings of perceived exertion in the prediction of heart rates during pregnancy. AB - When using Borg's 6-20 scale during pregnancy, ratings of perceived exertion (RPE) did not significantly correlate with exercise heart rates (HR) (P greater than 0.05). The HR predicted from RPE significantly (P less than 0.05) underestimated the exercise HR in the second trimester during walking (Group 1: mean difference 16 beats min-1, n = 11), aerobics classes (Group 4: mean 15 beats min-1, n = 48) and circuit training (Group 3: mean 18 beats min-1, n = 24); and in the third trimester during cycling (Group 2: mean 16 beats min-1, n = 12) and aerobics classes (Group 5: mean 11 beats min-1, n = 29). Maximal individual HR under-estimations were large for each physical activity during pregnancy, with values up to 54 beats min-1. Consequently, exercise intensity should not be monitored solely with RPE during pregnancy. PMID- 1623358 TI - Does exercise reduce all-cancer death rates? AB - A reanalysis is made of earlier data relating to initial physical fitness and the likelihood of death from all forms of cancer. It is argued that the original analysis may have been biased by an association between initial fitness and other health habits, particularly cigarette smoking. The association with fitness status remains after reanalysis of the data on the assumption that current smoking leads to a uniform doubling of the risk of cancer death, but the effect is weaker than previously reported. There remains some potential bias, in that the quantity of current smoking may have been linked to fitness status. Some 55% of deaths were untraced, but it is argued that any socioeconomic or other bias from this cause is likely to account for the association between cancer risk and low fitness status. Any reduction of cancer risk is associated with the change from an extremely sedentary to a moderately sedentary lifestyle. It thus cannot be explained in terms of the mechanisms previously invoked to explain low risks of colonic and reproductive cancers in endurance athletes. PMID- 1623359 TI - Menarcheal age among Indian sportswomen. AB - The subjects of the study were 85 Indian sportswomen from Delhi and the states of Uttar Pradesh, Punjab and Gujarat, and included outstanding players of cricket, hockey, kho-kho and table-tennis, who were winners of university, state or national championships. A sample of 77 subjects selected at random was used as the control. The recall procedures suggested by Damon and Bajema (1974) were used. The combined mean age at menarche for sportswomen is 13.56 years and for the control sample is 12.7 years. Menarche was significantly delayed in those sportswomen who embarked on physical training activities before the onset of menstruation. There are also variations in the mean menarcheal age between participants in different sports specialities. PMID- 1623362 TI - Sports medicine--where are the specialists? PMID- 1623361 TI - Volleyball injuries: a survey of injuries of Scottish National League male players. AB - Injuries sustained in male volleyball players in the first division of the Scottish National League during the 1989-1990 season were investigated by means of a questionnaire survey. Forty-six injuries were reported, representing an incidence of 0.53 injuries per player. Damage to muscles, tendons and ligaments accounted for most of the injuries. The cause of most injuries was blocking or spiking. In 74% of cases the injured players were able to resume training and playing within 2 weeks of the injury. In 10% of cases the injured players were unable to train or play for 7-14 weeks. PMID- 1623360 TI - Efficacy of perceptual versus heart rate monitoring in the development of endurance. AB - The purpose of this investigation was to compare the effectiveness of using ratings of perceived exertion (RPE) with heart rate in the monitoring of exercise intensity during aerobic dance instruction. Thirty-eight students who enrolled in aerobic dance classes used heart rate to monitor exercise intensity while 38 additional students used RPE to monitor exercise intensity during a 14-week course. Classes met twice a week for 50 min and all outside workouts were recorded. The groups did not differ with respect to the number of outside workouts. The dependent variable was endurance performance as measured by the distance run in 15 min. Data were analysed with a repeated measures analysis of variance (ANOVA) for multifactor experiments. There were significant trials (P less than 0.0001) and interaction (P less than 0.05) effects, and both groups improved significantly in endurance performance during 14 weeks of training. However, the group using RPE to monitor exercise intensity had a significantly greater gain in endurance. The heart rate group had a mean increase of 6% (166 m) whereas the RPE group increased 11% (274 m). It is concluded that during aerobic dance the monitoring of exercise intensity with RPE is associated with greater improvement in endurance than is heart rate monitoring. PMID- 1623363 TI - The National Sports Medicine Institute. 1. BASM's contribution to its formation. PMID- 1623364 TI - Parachuting injuries: a follow-up communication. PMID- 1623365 TI - Ocular fundus lesions in sports divers using safe diving practices. AB - Ocular fundus fluorescein angiography was performed on 26 divers, who had used safe diving practices for at least 10 years, and on seven controls. There was no significant difference in the incidence of macular abnormalities between these groups and those of a previous study. Adherence to safe diving practice confers some protection against the macular abnormalities known to occur in divers with a history of decompression sickness. PMID- 1623367 TI - Effect of breathing techniques on blood pressure response to resistance exercise. AB - Twenty novice male weight lifters performed resistance exercises using three different breathing techniques to determine the effects on blood pressure. Systolic and diastolic blood pressures were measured by an automated non-invasive method while subjects performed the single arm curl and double knee extension using the different breathing techniques. Performing the Valsalva manoeuvre (breath-holding) during either the single arm curl or double knee extension produced the highest blood pressure responses. Inhaling during the concentric phase of the exercise was associated with blood pressure elevations that were similar to the elevations observed with exhaling during the concentric phase. The heart rate response was slightly higher with inhalation. These results suggest that performing the Valsalva manoeuvre exaggerates the blood pressure response to resistance exercise. In addition, coupling inhalation with the concentric phase of the lift offers no cardiovascular advantage over coupling exhalation with the concentric phase of the lift. PMID- 1623366 TI - Ultrasonographic scan in knee pain in athletes. AB - Fifty-two knees were examined using real-time high-definition ultrasonography with a 7.5 MHz probe. The extra-articular structures were easily visualized and diagnosis of patellar tendon lesions and Baker's cysts formulated. While the meniscal cartilages were shown as a homogeneous triangular structure between the femoral condyle and the tibial plateau, no lesions were detected. Deeper intra articular structures, such as the cruciate ligaments, were not shown by the scan, thus their evaluation was not possible. Given its low cost, wide availability, non-invasiveness and patients' acceptability of the technique, ultrasonography may play an important role in the diagnosis of soft tissue lesions in and around the knee joint. PMID- 1623368 TI - A longitudinal study of the effects of television viewing on aggressive and prosocial behaviours. AB - A longitudinal study investigated the extent to which children's exposure to aggressive and prosocial television models in drama programmes influences their aggressive and prosocial behaviour. In The Netherlands we did not find significant positive correlations between prosocial behaviour and the viewing of prosocial behaviour on television. Positive correlations were found, however, between aggression and television violence viewing. This relationship disappeared almost completely when corrections for the starting level of aggression and intelligence were applied. The hypothesis, formulated on the basis of social learning theory, that television violence viewing leads to aggressive behaviour could not be supported. Our findings are further discussed and compared with the results found in the other countries participating in the international study. PMID- 1623370 TI - Personal computers and urological research. AB - The value of a computer in urological research depends not only upon an appropriate and informed choice of hardware, but also the purchase of software programs which will facilitate input, manipulation and transfer of relevant data. Acquaintance with the Data Protection Act is essential, as is registration as a data user in most cases. PMID- 1623369 TI - Transrectal ultrasound 1992. PMID- 1623371 TI - Psychological factors in recurrent uncomplicated urinary tract infection. AB - Recurrent urinary tract infection (UTI) is a very common medical complaint among women. A large proportion of such recurrence is attributable to a small sub-group of sufferers. Medical factors have proven insufficient to explain all such cases, and a number of psychological factors have been suggested as having a causal role. This study examines the evidence for the effects of behavioural and personality factors. Neuroticism and specific "risky" behaviours are identified as particularly important, being related to both the diagnosis of recurrent UTI and the frequency of infection. These findings suggest that treatment of recurrent, intractable UTI might include a psychological component. PMID- 1623372 TI - Extracorporeal shock wave lithotripsy with the Storz Modulith SL20: the first 500 patients. AB - Our initial experience of extracorporeal shock wave lithotripsy (ESWL) with the Storz Modulith SL20 is reported. A total of 500 patients with 551 renal and 120 ureteric stones, mean diameter 11.9 mm, underwent 746 treatments; 68.2% of patients required a single treatment. The mean treatment rate for renal calculi was 1.4 and for ureteric calculi it was 1.5, rising to 4.2 for staghorns; 62.2% of treatments were performed on an out-patient basis. Analgesia (intravenous fentanyl) was required in 60.9% of treatments for renal calculi but in only 38.2% of those for ureteric calculi. The overall stone-free rate at 3 months was 77.6%, with a further 14.7% of patients having fragments less than 3 mm in diameter that required no further treatment. The stone-free rate was dependent on the site of the stone, with the majority of residual fragments lying in a lower pole calix. There were few complications. The Modulith is an efficient and safe lithotripter capable of treating stones in the kidney and throughout the ureter. PMID- 1623373 TI - Percutaneous nephrolithotripsy for renal stones in over 1000 patients. AB - Over a period of 5 consecutive years, 1039 renal units were treated by percutaneous nephrolithotripsy for stone disease of the kidney. The success rate was 93.7%. Residual stones remained in 4.2% of patients and in 2.1% we failed to remove the stones. The complication rate was 17.8%. Complications were treated conservatively in most cases but nephrectomy was required on one occasion to control severe bleeding. The average hospital stay was 6.9 days. Follow-up of 339 renal units (333 patients), for a minimum of 60 months, revealed minor late sequelae such as pelviureteric junction obstruction in 1 patient (0.3%) and post catheterisation strictures of the anterior urethra in 4 (1.2%). Stone recurrence was observed in 9.1% of patients. Percutaneous nephrolithotripsy is an effective, safe treatment for renal stones with minimal late sequelae and is still required even in the era of extracorporeal shock wave lithotripsy. PMID- 1623374 TI - Hydatid disease of the urinary tract: evaluation of diagnostic methods. AB - Eight patients with histologically proven hydatid disease of the urinary tract underwent eosinophil count, ultrasonography (US) and computed tomography (CT). The findings were compared with those in 8 age-matched controls with simple renal cysts. Eosinophilia was not significantly different in the 2 groups. Mixed echogenicity on US and multivesicular cyst with mixed density on CT were the diagnostic features of hydatid cysts. Using these factors, both US and CT could diagnose or exclude hydatid disease in a significant number of patients with renal cysts. However, CT was more sensitive (88 vs 50%) and accurate (94 vs 75%) than US in the diagnosis of urinary tract hydatid disease. Retrograde pyelography confirmed communicating renal hydatid cysts in 2 patients. A practical algorithm for the investigation of urinary tract hydatid disease is suggested. PMID- 1623375 TI - Prognostic value of renal venous involvement in renal carcinoma. AB - A series of 108 renal tumour nephrectomies carried out between 1975 and 1984 was studied to determine the prognostic statistical significance of the relationship between venous involvement and various pathological features. Tumour size, spread, histological grade and lymph node involvement were compared between V0 tumours (58%), V1 (32%) and V2 tumours (10%). Actuarial 5-year survival rates revealed a poor prognosis with venous involvement (V0 66%, V1 27%, V2 33%). Tumours larger than 10 cm with perirenal spread and of higher histological grade were significantly related to venous involvement. Survival between renal vein involvement and inferior vena caval extension was statistically similar, but it was influenced by tumour size and higher grade. Perirenal spread and nodal involvement were poor indicators. PMID- 1623376 TI - Long-term results of surgical treatment of renal carcinoma in solitary kidneys by extracorporeal resection and autotransplantation. AB - We describe the technique and present the long-term results of extracorporeal partial nephrectomy and autotransplantation in 6 patients with renal carcinoma. During a follow-up period exceeding 5 years, dialysis was not required and the patients' blood pressure improved or remained within normal limits. One patient died post-operatively from gastrointestinal bleeding. The mean duration of follow up was 54 months (range 14-97). The alternatives to extracorporeal resection and autotransplantation (such as complete nephrectomy and in situ resection of the tumour) are discussed. PMID- 1623378 TI - Endometriosis of the ureter. AB - Five patients with ureteric endometriosis are described. Extensive pre-operative investigation failed to reveal the aetiology of the unilateral upper urinary tract obstruction seen in all of these patients. Due to the dense fibrosis that invariably accompanies ureteric endometriosis, early surgical excision of the ureteric stricture permits effective resolution of upper tract dilatation and improved renal salvage. PMID- 1623377 TI - Phase II clinical trial of recombinant alpha-2 interferon for biopsy-proven metastatic or recurrent renal carcinoma. AB - Twenty patients with histologically confirmed metastatic or recurrent renal carcinoma were treated in a phase II study with alpha-interferon (2-5 x 10(6) U/m2 subcutaneously, 3 times a week). Nineteen patients had multiple sites of disease and 18 had previously undergone nephrectomy; 9 had an ECOG performance status of 0.1, and 11 had a performance status of 2-3. There was one partial response, yielding an overall response rate of 5%. Treatment was well tolerated, although 7 patients developed influenza-like symptoms, and in 2 cases this was sufficiently severe for the patients to request cessation of treatment. As a single agent at this dose schedule, alpha-interferon has minimal activity in the treatment of renal carcinoma and cannot be recommended as standard therapy. The difference in outcome between this and some published series may reflect the stringent requirement for histological proof of the presence of metastases. PMID- 1623379 TI - Induction of carcinoma at ureterosigmoid anastomosis--with and without faecal stream. AB - The induction of tumours at the site of uretero-intestinal anastomosis was investigated in Hannover: WISTAR rats. The rats were divided into 3 groups. In one group (n = 70) the ureter of the left kidney was implanted into the colon, using microsurgical techniques developed for humans. In 13% of the rats in this group benign tumours developed; in 16% malignant tumours occurred. In a second group (n = 76) the ureter was implanted into a rectal bladder; the faeces were excluded from the anastomosis by a descending colon anus praeter. In this group benign tumours developed in 17% and malignant tumours in 8%, all of them being situated at the site of the anastomosis. In a control group (n = 80) no colonic tumour could be identified. PMID- 1623380 TI - Anti-reflux surgery by injection of Teflon paste. AB - Over a 3-year period, 55 refluxing ureters in 36 patients were treated by the endoscopic injection of Teflon paste. Although reflux was corrected immediately in 54 ureters (98%), reflux recurred 3 to 4 months later in 18 ureters. Reinjection was carried out once in 5 ureters and twice in 1. The success rate was 71% in primary reflux and 53% in secondary reflux. Significant side effects were encountered post-operatively in 3 patients: vesicoureteric junction obstruction in 2 and urethral stricture in 1. We recommend that the results of surgery should not be evaluated until at least 3 to 4 months after operation. A review of the literature shows that the overall success rate was 92% in 367 ureters with primary reflux and 70% in 181 ureters with secondary reflux. Because of the uncertain outcome of surgery and the possibility of adverse side effects, one should be cautious when considering this form of treatment in young children. PMID- 1623381 TI - Abscess of urachal remnant mimicking urinary bladder neoplasm. AB - Three cases of urachal abscess with extensive interstitial inflammation and fibrosis are reported. Clinically, all patients had a lower abdominal mass and CT scan and ultrasonic examination revealed a large tumour located anterior or superior to the bladder. They all underwent laparotomy and had either a partial cystectomy or an en bloc resection of the bladder and adjacent organs due to severe adhesions. Microscopic examination of the specimens revealed no evidence of carcinoma and only abscess formation with extensive chronic interstitial inflammation and fibrosis were seen. In one case, residual columnar epithelium suggestive of urachal origin was identified in the abscess cavity. Urachal abscess should be considered when dealing with lower abdominal masses. PMID- 1623382 TI - Continent urinary reservoirs. AB - We report our experience of 30 continent urinary reservoirs (CURs) after radical cystectomy. The patients ranged in age from 35 to 70 years. There were 22 males and 8 females. Pre-operative urograms showed normal upper tracts in 22 patients, unilateral hydronephrosis in 4 and bilateral hydronephrosis in 4. The first 20 patients had a standard CUR procedure and the last 10 had a modified CUR. The mean operative time, blood loss and post-operative stay were 6.6 h, 900 ml and 25 days respectively for standard CURs and 5.7 h, 825 ml and 21 days respectively for the modified CURs. Post-operative, urinary leaks from the caecostomy site occurred in 2 patients (1 of which was fatal) while 3 other patients had prolonged ileus, burst abdomen and intestinal obstruction probably due to non demonstrable urinary leaks. All 5 complications occurred in the first 20 patients. Upper tract status was evaluated in 28 patients 3 months after surgery and showed normal upper tracts in 19 patients, improvement in 6 (35%) and worsening in 3 (12.5%). Pouchograms showed no reflux in 25 patients, unilateral reflux in 2 and bilateral reflux in 1. Complete continence was achieved in 25 patients--2 of them had revision surgery, giving a success rate of 89% with a follow-up of 6 to 48 months (median 24). The remaining 3 patients were incontinent. PMID- 1623383 TI - Cystodiathermy under local anaesthesia using the flexible cystoscope. AB - The use of the flexible cytoscope in the follow-up of patients with bladder carcinoma is becoming more widespread. In a series of 17 patients, cystodiathermy of small recurrent tumours using the flexible cytoscope and topical urethral anaesthesia proved to be a safe, effective and well tolerated procedure. PMID- 1623384 TI - Natural history and prognosis of prostate carcinoma in adolescents and men under 35 years of age. AB - Prostate cancer is extremely rare in men under 35 years of age. The tumour is invariably poorly differentiated and aggressive, with rapidly growing bulky soft tissue metastases and negative tumour markers. Bone metastases develop late and are usually osteolytic. The disease responds poorly to radiation or hormonal therapy and is too advanced at presentation for radical surgery. Chemotherapy appears to be of some benefit, though in the majority of cases death occurs within a year. We describe a 31-year-old man with carcinoma of the prostate. A review of the literature is presented. This is the first patient in whom the epithelial origin of the prostate cancer was confirmed by immunoperoxidase staining with prostatic specific antigen. Plasma prostatic specific antigen was normal despite a large tumour burden and widespread metastases. He did not respond to conventional treatment. The phenotypic expression and biological behaviour of these tumours are distinct from those occurring in men beyond the fourth decade. PMID- 1623385 TI - Vesicoureteric reflux in sibships. AB - A family with 4 of 6 siblings manifesting vesicoureteric reflux is presented. Reflux could not be demonstrated in preceding and succeeding generations in this family. Genetic analysis suggests that most instances of familial vesicoureteric reflux arise secondary to expression of autosomal dominant single genes with incomplete penetrance. Screening of sibships for reflux might be most appropriately carried out by urine analysis, culture and ultrasound imaging. PMID- 1623386 TI - Multicystic renal dysplasia detected by prenatal ultrasonography. Natural history and results of conservative management. AB - In a review of 44 infants with multicystic renal dysplasia diagnosed prenatally by ultrasonography, contralateral anomalies, bilateral disease and other non urinary congenital anomalies were rare. In approximately two-thirds of infants the lesion was impalpable and in 2 cases involution had occurred prenatally. All but 5 were managed conservatively and without complications, and partial or complete involution of the lesion occurred in more than 50% during follow-up. It was concluded that the natural history of this anomaly is usually benign and that conservative management is advisable. PMID- 1623387 TI - Localised infarction of the testis. PMID- 1623388 TI - Perforation of bladder carcinoma presenting as acute abdomen. PMID- 1623389 TI - Generalised seizure after extracorporeal shock wave lithotripsy. A complication easy to prevent? PMID- 1623390 TI - Fournier's gangrene: an aetiological hypothesis. PMID- 1623391 TI - Paneth and argyrophil cells in prostatic carcinoma. PMID- 1623392 TI - Giant bladder diverticulum causing urethral obstruction in an infant. PMID- 1623393 TI - Abdominoscrotal hydrocele. PMID- 1623394 TI - Why renography can fail in the diagnosis of upper urinary tract obstruction. PMID- 1623395 TI - Reverse supine position on lithostar for lower ureteric stones. PMID- 1623397 TI - Re: A comparison of aspiration, antazoline sclerotherapy and surgery in the treatment of hydrocele. PMID- 1623396 TI - One-step dilatation of the corpus cavernosum by cardiac valve dilators. PMID- 1623398 TI - Different populations of cells in the suprachiasmatic nuclei express c-fos in association with light-induced phase delays and advances of the free-running activity rhythm in hamsters. AB - Circadian rhythmicity is controlled by a light-entrainable pacemaker located in the suprachiasmatic nuclei (SCN) of the mammalian hypothalamus. Brief light exposure during the subjective night causes phase shifts of the free-running activity rhythm and expression of c-fos-related proteins (Fos) among a population of cells in the hamster SCN. Light exposure (30 lux for 15 min) during the early subjective night (CT13) causes phase delays (-60 +/- 12 min), while exposure at mid-subjective night (CT18) causes phase advances (114 +/- 48 min) of the free running activity rhythm. Light exposure at mid-subjective day (CT6) does not cause phase alterations of the rhythm. Similarly, only light exposure at CT13 or CT18 induces Fos expression in the SCN. The distribution of Fos-immunoreactive cells in the SCN is more widespread in animals stimulated with light at CT18. In addition, a group of cells located dorsal and anterior to the SCN express Fos only after stimulation at CT18. The data are consistent with the hypothesis that Fos expression represents an event in the signal transduction pathway leading to light-induced alterations in circadian pacemaker function. Furthermore, the data raise the possibility that different populations of cells in the suprachiasmatic hypothalamus may participate in light-induced phase advances and delays of the circadian pacemaker. PMID- 1623399 TI - The functional relationship between antidromically evoked field responses of the dentate gyrus and mossy fiber reorganization in temporal lobe epileptic patients. AB - Field recordings from the dentate granule cell layer of in vitro brain slices of temporal lobe epileptic patients were evoked by antidromic stimulation. Tissue from the same specimen was stained by the Timm-sulfide method to assess the pattern and degree of mossy fiber reorganization into the supragranular layer. A wide range of physiological responses and Timm staining patterns was present across patients. A significant correlation was observed between the abnormality of antidromic responses, reflected by multiple secondary population spikes, and the degree of Timm staining of the supragranular layer. This relationship lends support to the hypothesis that mossy fiber synapses located in the supragranular layer may have functional implications for granule cell excitability in human epileptic tissue. PMID- 1623400 TI - Ectopic discharge in injured nerves: comparison of trigeminal and somatic afferents. AB - Using the teased fiber recording method, we have compared pathophysiological properties of afferent axons injured in the infraorbital nerve (ION) vs the sciatic nerve in rats. Both myelinated and unmyelinated axons ending in ION neuromas produced much less ongoing discharge than those ending in sciatic nerve neuromas. Similarly, mechanosensitivity and acute injury discharge in ION neuromas were minimal. These differences may be related to the different spectrum of neuropathic symptomatology associated with nerve injury in the trigeminal vs the segmental innervation fields. PMID- 1623401 TI - Interactions of fluoxetine with metabolism of dopamine and serotonin in rat brain regions. AB - Given evidence of inhibitory effects of serotonin on dopaminergic neurotransmission, a series of experiments sought neurochemical evidence of interactions between the selective serotonin transport inhibitor fluoxetine and the metabolism of dopamine (DA) or serotonin (5-HT) in regions of rat brain that might account for extrapyramidal side-effects associated with clinical use of fluoxetine. There were significant inhibitory effects of acute or repeated fluoxetine treatment on the turnover of 5-HT (accumulation of 5 hydroxytryptophan, or ratio of [5-hydroxyindoleacetic acid]/[5-HT]) in striatum, nucleus accumbens and frontal cerebral cortex, but only minor effects on metabolism of DA (accumulation of dihydroxyphenylalanine, or [homovanillic acid]/[DA] ratio), even at high doses or with repeated treatment, and no significant inhibition of the DA metabolism-increasing actions of haloperidol. PMID- 1623402 TI - Effects of selective toxic lesions of cholinergic neurons of the laterodorsal tegmental nucleus on experimental seizures. AB - This study determined the effects of bilateral discrete partial lesions of cholinergic neurons of the laterodorsal tegmental nucleus (LDTg) of the pontomesencephalic tegmentum on seizures induced by intravenous pentylenetetrazol (PTZ). Relatively selective lesions produced by bilateral 50 nl microinjections of 75 pmol of the cholinergic neurotoxin ethylcholine mustard aziridinium ion (AF64A) resulted in a significant reduction in the threshold of myoclonic and facial-forelimb clonic seizures but not tonic seizures when PTZ was infused 7 days later. This demonstrates that this cholinergic nucleus is a key site of subcortical seizure regulation. We propose that this control is mediated by ascending projections from the LDTg to the central medial intralaminar nucleus of the thalamus. PMID- 1623403 TI - Spontaneous miniature hyperpolarizations of presynaptic nerve terminals in the chick ciliary ganglion. AB - Intracellular recordings from presynaptic nerve terminals in the chick ciliary ganglion revealed the presence of spontaneous miniature hyperpolarizations in virtually all (approximately 86%) nerve terminals examined. These spontaneous events appeared as small, brief hyperpolarizations at resting potential and were observed to increase or decrease as the membrane potential was depolarized or hyperpolarized from rest, respectively. The hyperpolarizing potentials were sensitive to blockade by tetraethylammonium and Ba2+, while caffeine increased then abolished these events. The voltage fluctuations were unaffected by tetrodotoxin, low Ca2+ external solution or the synaptic blockers, picrotoxin and strychnine. These spontaneous, transient, miniature hyperpolarizations may be due to the brief and co-ordinated activation of between 15-60 Ca(2+)-dependent K+ channels following the release of Ca2+ from internal stores. PMID- 1623405 TI - The effect of direct current field polarity on recovery after acute experimental spinal cord injury. AB - Recent evidence indicates that direct current (DC) fields promote recovery of acutely injured central and peripheral nervous system axons. The polarity of the applied DC field may play an important role in modulating these effects. In the present study, the effect of DC field polarity on recovery of injured spinal cord axons was examined anatomically, electrophysiologically and behaviourly in a rat model. After a 53 g clip compression injury of the cord at T1, 30 adult rats were randomly and blindly allocated to one of three groups (n = 10 each): one group received implantation of a DC stimulator (14 microA) with the cathode caudal to the injury site; the second group received implantation of a similar stimulator with the cathode rostral to the injury site; and the third group received a sham (O microA) stimulator. Clinical neurological function was assessed by the inclined plane technique and axonal function was assessed by motor- and somatosensory-evoked potentials (MEP and SSEP). A quantitative assessment of axonal integrity was performed by counting neurons in the brain retrogradely labelled by the axonal tracer horseradish peroxidase (HRP) and by counting axons at the injury site. The inclined plane scores (P less than 0.0001), MEP amplitude (P less than 0.02), counts of neurons retrogradely labelled by HRP (P less than 0.0001), and axon counts at the injury site (P less than 0.01) were significantly greater in the group treated with a DC field with the cathode caudal to the lesion than in the other two groups. Conversely, the cathode rostral DC field caused a decrease in the number of neurons retrogradely labelled by HRP (P less than 0.05) compared to the sham and cathode caudal groups. These data confirm our previous finding that DC fields promote recovery of acutely injured spinal cord axons. Furthermore, the polarity of the applied field is of critical importance to this effect. PMID- 1623404 TI - Co-localization of hyaluronic acid and chondroitin sulfate proteoglycan in rat cerebral cortex. AB - The distribution of hyaluronate (HA) and chondroitin sulfate (CS) proteoglycan in the rat cerebral cortex was compared. For the localization of HA, the sections were incubated with human glial hyaluronate-binding protein (GHAP) and then reacted with monoclonal or polyclonal antibodies to GHAP. Polyclonal antibodies raised in rabbit were used for double-labeling experiments with monoclonal antibodies raised in mice and reacting with CS proteoglycans. Little reactivity was observed in rat cerebral cortex with polyclonal GHAP antibodies if the sections were not incubated with GHAP. Monoclonal antibodies to GHAP did not react with murine tissues. CS proteoglycans were localized in chondroitinase digested sections with monoclonal antibodies reacting with the 4-sulfated oligosaccharide stubs formed by the digestion with chondroitinase ABC of CS side chains. In the rat cerebral cortex, the distribution of CS proteoglycans was similar to that reported by Bertolotto, A., Rocca, G. and Schiffer, D., J. Neurol. Sci., 100 (1990) 113-123, and his collaborators using the same antibodies. Many neurons mainly located in the upper and deep cortical layers were surrounded by CS immunoreactive material. Several (but not all) CS-positive neurons also stained for HA with an identical distribution except that in most instances the staining was confined to the periphery of the perikaryon and did not extend to the dendritic tree. The finding suggests that cerebral cortex CS proteoglycan is capable of interacting with HA. PMID- 1623406 TI - Pharmacogenetic assessment of the effects of carbamazepine on cocaine-kindled and cocaine-induced seizures. AB - The effects of chronic carbamazepine (CBZ) on the development and expression of cocaine-kindled seizures and seizures produced by an acute injection of cocaine were evaluated in BALB/cByJ, C57Bl/6J and SJL/J mice. The repeated administration of a subconvulsant dose of cocaine initially resulted in the development of an increased sensitivity to the convulsant effects of cocaine in the three strains. Chronic, dietary carbamazepine attenuated this initial sensitization to cocaine induced seizures. While the continued administration of cocaine resulted in a relatively permanent sensitization to cocaine-induced seizures among SJL mice, tolerance to cocaine-induced seizures ultimately developed among C57 mice and to a lesser degree among BALB mice. Genetic factors were found to mediate the effects of chronic CBZ on the development of sensitization and/or tolerance to the convulsant effects of cocaine. Among BALB mice, chronic CBZ appears to have eliminated the development of tolerance to cocaine-induced seizures and allowed an underlying sensitization to be manifest. Among SJL mice, however, the sensitization observed following repeated cocaine injections was reduced, but not eliminated. Genetic factors were also found to be associated with the effects of CBZ on seizures induced by the acute administration of cocaine. BALB and C57 mice, but not SJL mice, chronically treated with dietary CBZ were less susceptible to a consulvant dose of cocaine than their corresponding dietary controls for at least 72 h after stopping CBZ administration. In addition, there were genotype-specific lethal effects associated with the concurrent administration of CBZ and cocaine. PMID- 1623407 TI - Efferent microvascular responses to electrical stimulation of the area postrema in rats. AB - As part of its role to transduce blood-borne and afferent neural stimuli to the brain, the area postrema conducts efferent projections monosynaptically to individual nuclei of the medulla oblongata and pons. We hypothesized that electrical activation of the area postrema would mimic this transduction process and couple microvascular responses in efferent sites to local increases in tissue metabolism reported previously. We used quantitative autoradiographic techniques and image analysis to measure capillary transfer constants for [14C]alpha aminoisobutyric acid (AIB, a small, neutral amino acid) and blood flow (iodo[14C]antipyrine) in individual brainstem structures of anesthetized rats. The area postrema was stimulated electrically by means of a monopolar microelectrode positioned stereotaxically 100 microns deep in the dorsocentral aspect of the organ. There were no significant effects of stimulation on [14C]AIB influx or blood flow in control hindbrain structures where postremal projections are sparse or absent--the spinal trigeminal nucleus, reticular formation, or cerebellar vermis. Stimulation of the area postrema produced equivalent increases in transcapillary influx of [14C]AIB and capillary blood flow in the nucleus of the solitary tract, dorsal motor nuclei of the vagus nerves, ventrolateral medullary C1 region, locus coeruleus, dorsal tegmental nuclei, and lateral parabrachial nuclei. Formation of ratios interrelating rates of [14C]AIB influx and blood flow with previously assessed values of tissue glucose metabolism indicated that these measures increased proportionately during postremal stimulation. Such proportional increases in capillary [14C]AIB transfer and blood flow during tissue activation by area postrema stimulation are consistent with interpretation that the increase in blood flow resulted from recruitment of unused surface area in the capillary networks of individual efferent nuclei.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623408 TI - Spinal projections of the locus coeruleus and the nucleus subcoeruleus in the Harlan and the Sasco Sprague-Dawley rat. AB - The descending projections of the locus coeruleus (LC) and the nucleus subcoeruleus (SC) to the lumbar spinal cord were examined in rats from two vendors using retrograde transport of fluorescent latex beads. There was a vendor difference observed which agrees with previous findings. The differential dorsal horn and ventral horn projections of the Harlan and the Sasco Sprague-Dawley rats, reported by Fritschy and Grzanna, and Clark and Proudfit were confirmed. In the Harlan rat more cells were labeled in the LC following injections in the dorsal horn. In contrast, in the Sasco rat, more cells were labeled in the LC from injections in the ventral horn. Although, in all studies, the LC in rats from these vendors projected to some extent to both the dorsal and the ventral horn. A difference in labeling was noted also for the depth of placement of the tracer in the dorsal horn. When the site of injection was in the nucleus proprius, a predominantly contralateral projection of the LC was noted. In contrast, when horseradish peroxidase (HRP) gel implants were placed to include the superficial laminae, the cells in the LC were labeled predominantly ipsilaterally. The SC has a major projection to the dorsal horn in the Harlan rats while cells in the SC were predominantly labeled following ventral horn injection in the Sasco rats. These cells send mostly ipsilateral projections to the dorsal and ventral horn of the spinal cord. Double labeled studies confirmed that 91% of LC and 86% of SC neurons projecting to the spinal cord were noradrenergic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623410 TI - Interactions of ibogaine and D-amphetamine: in vivo microdialysis and motor behavior in rats. AB - Ibogaine, an indolalkylamine, has been proposed for use in treating stimulant addiction. In the present study we sought to determine if ibogaine had any effects on the neurochemical and motor changes induced by D-amphetamine that would substantiate the anti-addictive claim. Ibogaine (40 mg/kg, i.p.) injected 19 h prior to a D-amphetamine challenge (1.25 mg/kg, i.p.) potentiated the expected rise in extracellular dopamine levels in the striatum and in the nucleus accumbens, as measured by microdialysis in freely moving rats. Using photocell activity cages, the same ibogaine pretreatment enhanced the stimulatory motor effects induced by a wide range of D-amphetamine doses (0.625, 1.25, 2.5 or 5 mg/kg, i.p.). These findings suggest that ibogaine might increase the reinforcing efficacy of D-amphetamine. However, since high doses of D-amphetamine can be aversive, the potentiation of D-amphetamine's effects by ibogaine might also lead to a decrease in the reinforcing efficacy of D-amphetamine. PMID- 1623409 TI - Studies on long-term potentiation of the population spike component of hippocampal field potential by the tetanic stimulation of the perforant path rats: effects of a dopamine agonist, SKF-38393. AB - Long-term potentiation of the field potentials recorded in the dentate gyrus of the hippocampus was observed in freely-moving rats by delivering a brief tetanic stimulation to the perforant path, and the effects of the D1 agonist, SKF-38393, on it was investigated. The field potential was divided into two components; excitatory postsynaptic potential (EPSP) and population spike. In Expt. I, synaptic stimulus-response (S-R) relationship, spike S-R relationship, and EPSP spike (E-S) relationship were plotted. The estimated slope of the regression line in the spike S-R relationship was enhanced after delivery of the tetanic stimulation (10 pulse at 400 Hz), where that in synaptic S-R relationship was not enhanced. The estimated slope of the regression line in the E-S relationship was also enhanced by the tetanic stimulation. In Expt. II, time-dependent change of the field potential after tetanic stimulation was investigated. The population spike was enhanced significantly for about 2 h following tetanic stimulation, while pEPSP did not change significantly. These changes following tetanic stimulation in Expt. I and II were significantly inhibited by previous administration of SKF-38393 (10 mg/kg, i.p.), and the effect of this drug was dose-dependently antagonized by the D1 antagonist, SCH-23390 (0.1, 0.2 and 0.5 mg/kg, i.p.). These results suggest that a brief tetanic stimulation of the perforant path induces long-term potentiation of the population spike without potentiating the synaptic input in the perforant path-dentate synapses, and that potentiation of the population spike is inhibited by the dopaminergic D1 mechanism. PMID- 1623411 TI - Evidence for two different afferent pathways carrying stress-related information (noxious and amygdala stimulation) to the bed nucleus of the stria terminalis. AB - The bed nucleus of the stria terminalis (BNST) is an important nucleus involved in mediating amygdala-regulated endocrine effects. Since the amygdala is important in mediating the endocrine response to noxious somatosensory stimuli and olfactory stimulation, this experiment studies whether noxious input (tail pinch, TP) and stress-related input (amygdala stimulation, AmygS) will modulate BNST neuronal activity. One hundred and fifty-eight BNST neurons were studied following AmygS, TP and cutaneous stroke. AmygS was effective in 66% of BNST neurons and produced one of the following five responses: oligosynaptic excitation (43%), polysynaptic excitation (5%), time-locked inhibition (4%), generalized increase in firing rate (8%), or generalized decrease in firing rate (6%). TP produced an increase in firing rate in 27% of BNST neurons tested. Analysis of a contingency table constructed to determine the degree of correspondence between neurons responsive to AmygS and neurons responsive to TP showed that the distributions of reactivity to these stimuli in BNST neurons are independent of each other. This suggests that although AmygS and TP are both capable of altering the firing rate of BNST neurons, the pathways by which they reach BNST differ. PMID- 1623412 TI - Regional quantitative permeability of blood-brain barrier lesions in rats with chronic renal hypertension. AB - Blood-brain transfer constants for a small, neutral amino acid tracer, [14C]alpha aminoisobutyric acid (AIB), were measured by quantitative autoradiography and image analysis in 15 individual brain structures of 2-kidney, 1-clip renal hypertensive rats (RHR) and age-matched normotensive controls (NR). Mean arterial pressures (MAP) for 4 month-old RHR and NR were 182 +/- 19 and 121 +/- 3 mmHg, respectively. Most brain structures in RHR had very low [14C]AIB transfer constants similar to those in NR (1-3 microliters.g-1.min-1), indicative of normal blood-brain barrier (BBB) function. Focal lesions, however, having transfer constants 2-7x normal and measuring less than 1.7 mm2 in area, appeared in RHR primarily in the cerebellar vermian and cerebral cortices. Chronic unilateral cervical sympathectomy did not influence the incidence or magnitude of BBB lesions in the denervated hemisphere of RHR. Acute arterial hypertension produced by systemic infusion of phenylephrine (elevation of MAP in RHR by 43%) increased the incidence and magnitude of lesions by 48% and 2-12x, respectively, although many brain regions in acutely hypertensive RHR retained normal permeability to [14C]AIB. The results demonstrate normal BBB permeability for much of the brain in chronic renal hypertension, with focal lesions having 7x or less the normal rate of blood-brain transfer for a small physiological probe. PMID- 1623413 TI - Individual perching behavior of laying hens and its effects in cages. AB - 1. ISA Brown hens were housed, from 18 to 71 weeks of age, as groups of 4 in cages with 675 cm2/bird. There were 7 treatments: control cages and 6 treatments with perches fitted across the rear of the cage. Five treatments had 450 mm wide cages, with perches made from hardwood, textured metal, smooth plastic, softwood and padded vinyl, and one treatment had a 600 mm wide cage, with a softwood perch. There were 4 cages in each of the first 6 treatments and 6 in the last. 2. Overall, birds spent about 25% of the day time on perches. Most time (28 to 41%) was spent perching on the 600 mm softwood perches. Among 450 mm perches, most time (25 to 30%) was spent on the softwood perch and least (13 to 23%) on the plastic; the results suggested that a slightly rough surface was preferred. Individual birds varied considerably in the proportion of day time they spent perching; this variation was relatively consistent over time. 3. Overall, the proportion of birds roosting on the perches at night was 85% in period 1; declined to 76% by period 6, probably because increased body size made it almost impossible for 4 birds to perch in the 450 mm cages. Birds roosting on the floor tended always to be the same individuals. 4. Damage to the soles of the feet was less in all treatments with perches than in control cages. It was least in 600 mm wide cages and showed a negative correlation with time spent perching, both within and between treatments. Long or twisted claws, in contrast, tended to be slightly worse in treatments where there was most perching. 5. Downgraded eggs tended to be slightly more frequent in cages with perches; the greatest proportion (cracked 1.4%, dirty 3.6%) was from the 600 mm wide cages, as a result of hens laying from the perch and a build-up of manure behind it. 6. Although problems remain the findings suggest that provision of perches is important for the welfare of hens; perch space should be sufficient to allow all birds to perch simultaneously. PMID- 1623414 TI - A study of heat production and heat loss in crated broiler chickens: a mathematical model for a single bird. AB - 1. A steady state model of heat production and loss in crated broiler chickens is presented. 2. The model is based on physiological factors and uses experimental data from various sources. 3. Although many of the required parameters are not well defined at present, the model allows a better understanding of the processes which lead to hyperthermic stress in crated broiler chickens, and is relevant to the design of ventilation systems for poultry transporters. PMID- 1623415 TI - Effects of photostimulation at 18, 24 and 30 weeks of age on the productivity of female turkeys fed ad libitum or restricted until point of lay. AB - 1. Turkey females were fed ad libitum or restricted from 6 weeks of age to achieve mean body weights of 0.6 of ad libitum fed birds on photostimulation at 18, 24 or 30 weeks of age. Body weight, food intake, egg production and hatchability were recorded to 54 weeks of age. 2. Restricted turkeys were fed ad libitum after first egg or 36 weeks of age. Food intake after 30 weeks of age averaged 170 g/bird/d and was similar for all treatments. At 54 weeks of age, restricted turkeys photostimulated at 24 and 30 weeks were not as heavy as turkeys photostimulated at 18 weeks and ad libitum fed turkeys. 3. A large proportion of restricted turkeys photostimulated at 18 weeks of age did not commence lay until 30 to 40 weeks and a significant number of restricted birds photostimulated at 24 weeks had short laying cycles. Restricted birds photostimulated at 30 weeks came into lay and showed similar persistency of lay to ad libitum fed turkeys. 4. Ad libitum fed turkeys laid 115.0, 122.0 and 101.0 and restricted turkeys 92.4, 99.5 and 103.4 eggs when photostimulated at 18, 24 and 30 weeks, respectively. The number of non-settable eggs was lower in restricted compared with ad libitum fed turkeys and declined with age at photostimulation. 5. Egg size at the end of the experiment was similar for ad libitum fed turkeys and restricted birds photostimulated at 18 weeks but was 2.3 g lower for restricted birds photostimulated at 24 and 30 weeks of age. 6. Hatchability was higher, and the proportion of second quality poults was lower with eggs from restricted turkeys. The mean numbers of poults hatched were 59.9, 75.1 and 66.0 for ad libitum fed and 71.7, 65.7 and 79.4 for restricted turkeys photostimulated at 18, 24 and 30 weeks of age. PMID- 1623416 TI - Metabolic and behavioral adaptation of light-bodied chicks to meal feeding. AB - 1. Two-week-old male chicks of a light-bodied strain were fed one (1M) or two (2M) 2-h meals per day. An additional group was pair-fed (P1M) the amount consumed by the 1M group on the previous day. 2. After 21 days, final body weight of the 1M and 2M chicks attained 65% and 80%, respectively, of that of the control group fed ad libitum. The weight gain of the P1M chicks was equal to that of the 1M chicks. 3. Food consumption of chicks adapted to meals was not even throughout the feeding period. On day 16 of the experiment, the 1M birds consumed 65% of the meal during the first 30 min. P1M chicks behaved similarly to the 1M ones. The intake of the 2M chicks during each meal was exactly half of their daily consumption, despite the uneven time period between meals. 4. The time during which food remained in the gastrointestinal tract (GIT) was longer under the meal feeding regimes than in the ad libitum-fed groups. 5. Although neither body composition nor metabolisable energy was affected by meal regime, food utilisation was poorer in the 1M and P1M than in the ad libitum and 2M-fed chicks. PMID- 1623418 TI - Incidence of non-laying in domestic hens. AB - 1. Egg production records of 31,455 individually caged hens, 27 to 34 weeks of age and of 4 genotypes, were examined. 2. Sixty-nine non-layers were identified in the 30 to 40 week age group, and examined post mortem; an incidence of 2.1 per 1000. 3. Some of the 69 individuals had more than one abnormality. Forty-two percent were internal layers, 34% had some form of neoplasia, 24% had an abnormal or diseased oviduct, 18% were sex reversals, 16% had a diseased ovary, 8% were of poor condition and considered culls, and 7% were in good condition, but with small, immature ovaries. 4. Of 54 birds not in lay at 27 weeks, 43 (80%) had come into lay by 34 weeks of age. 5. Genotype influenced the incidence of neoplasia and, in turn, the number of non-layers. PMID- 1623419 TI - Enhanced induction of hepatic lipid peroxidation by ferric nitrilotriacetate in chickens susceptible to fatty liver rupture. AB - 1. Two strains of single comb White Leghorn birds, one susceptible to fatty liver rupture (UCD-003) and a normal commercial strain, were injected with iron nitrilotriacetate and the extent of hepatic lipid peroxidation that occurred was estimated by measuring concentrations of malondialdehyde (MDA). 2. Higher concentrations of MDA were found in the livers of the UCD-003 strain than in the normal birds after injection of iron nitrilotriacetate. No differences were found in the activities of glutathione peroxidase, superoxide dismutase and catalase in the livers of untreated birds of either strain. 3. The degree of unsaturation of the fats in the livers of the two strains was similar. However, the UCD-003 birds had a significantly higher content of liver fat than the normal birds. The increased concentrations of liver fat could account for the increased lipid peroxidation in the UCD-003 birds. 4. The increased incidence of liver haemorrhage that occurs in the UCD-003 birds may be caused by the increased susceptibility of these birds to hepatic lipid peroxidation. PMID- 1623417 TI - An allometric-autoregressive approach to poultry development. AB - 1. The relative rates of development in a commercial layer and a broiler strain of chicken fed 180 or 230 g crude protein/kg were investigated by the use of the allometric-autoregressive model. Development was divided into pre-pubertal (0 to 8 weeks) and pubertal phases (8 to 22 weeks). 2. Significant strain effects were observed, at all ages, in rates of gain of live (L) body mass, carcass (C) mass, non-carcase (N) mass and empty-body (EB) mass as well as C, N and EB moisture, protein and fat content. 3. Significant dietary effects were observed in C and EB fat in the pre-pubertal phase and L mass, N protein and C fat in the subsequent pubertal period. PMID- 1623420 TI - Comparison between wheat, triticale, rye, soyabean oil and strain of laying bird on the production, and cholesterol and fatty acid contents of eggs. AB - 1. The effects of feeding three types of cereal grain (wheat, triticale or rye) and soyabean oil (0 or 20 g/kg) over a 12-week period on the production, yolk cholesterol and yolk fatty acid concentrations of three strains of laying pullets were studied. 2. Pullets fed on wheat- or triticale-based diets had higher body weight gains, egg productions, egg weights, egg mass and lower yolk cholesterol concentrations than pullets fed on rye-based diets. However, there were no significant differences between the cereals in yolk cholesterol content. 3. There were no significant differences between the three cereals in total food consumption of pullets nor of yolk weight nor yolk concentration of palmitic, stearic and oleic acids. 4. Pullets fed on triticale-based diets had higher yolk linoleic acid concentrations and lower yolk oleic acid: linoleic acid ratios than pullets fed on rye- or wheat-based diets. 5. Soyabean oil supplementation increased egg production, egg mass, yolk linoleic concentration and yolk unsaturated to saturated fatty acid ratio, but reduced yolk oleic acid: linoleic acid ratio. 6. There were differences between strains of pullets in weight gain, food consumption, rate of lay, egg weight and yolk cholesterol, but not in yolk fatty acid concentrations. 7. It was concluded that wheat- or triticale-based diets gave good production of eggs of lower cholesterol content, that soyabean oil supplementation gave eggs with a high unsaturated to saturated fatty acid ratio and that two strains of layers produced eggs with lower yolk cholesterol concentrations than a third strain. PMID- 1623421 TI - Nutritional value of naked oats (Avena nuda) in laying hen diets. AB - 1. Two experiments were conducted to evaluate the use of naked oats (NO) in layer diets. In experiment 1 the use of NO supplemented with minerals, vitamins and lysine was examined. In experiment 2 layers were fed equicaloric and isonitrogenous diets containing 0-66% NO. 2. Layers fed ground NO supplemented with minerals, vitamins and lysine for 6 weeks exhibited a significant depression in food intake, egg production, egg weight and shell strength. 3. Substitution of NO at 20-66% resulted in performance comparable to that of birds fed a maize soyabean meal diet for 12 weeks. Food intake was reduced in the first week of the experiment in birds fed diets with NO; thereafter, treatment effects were not detected. Yolk colour index progressively decreased as dietary inclusion of NO increased. 4. It is concluded that naked oats can be used at levels up to 66% in layer diets to replace all or part of the maize and part of the soyabean meal without any reduction in performance. PMID- 1623422 TI - Dietary phosphorus and food allowance of dwarf breeders affect reproductive performance of hens and bone development of their progeny. AB - 1. An experiment was conducted with 144 caged hens to study the effects of different dietary concentrations of phosphorus and of food restriction on the reproductive performance of dwarf breeder hens and on the growth and the bone development of their progeny. 2. Severe food restrictions at 105 g/hen day compared to 115 g/hen day, decreased hen body weight and hen day egg production. Fertility was unaffected and hatchability slightly depressed by the more severe restriction. 3. Egg and one-day-old chick weights were decreased by limiting the food intake of the breeders but the negative effect disappeared at slaughter (7 weeks). 4. Shell quality decreased as the dietary phosphorus increased and was not affected by food allowance. Albumen quality was slightly impaired in severely restricted hens. 5. Serum inorganic phosphorus in hens and yolk phosphorus increased with increasing dietary phosphorus. Tibial breaking strength and tibial percentage ash of the progeny at hatching was markedly improved in proportion to maternal phosphorus and food intake. This improvement in bone quality was not maintained at 7 weeks. 6. The number of chicks affected by twisted legs (valgus) and dyschondroplasia were similar whatever the maternal diet. The frequency of valgus was higher in males than in females. 7. It is concluded that maternal food intake and phosphorus supply are of importance for the initial bone development of the progeny. PMID- 1623423 TI - Lack of effect of dietary energy-to-protein ratio and energy concentration on the response of broiler chickens to virginiamycin. AB - 1. Two factorial experiments were carried out with male broiler chicks from 6 to 28 (experiment 1) and from 7 to 49 (experiment 2) d of age to evaluate the combined effect of virginiamycin (VIR), dietary energy concentration, and energy to-protein (E:P) ratio on performance and the utilisation of dietary nutrients. 2. VIR had no significant effect in either experiment on food intake or weight gain, but significantly improved food efficiency up to 28 d of age (P less than 0.001 and P less than 0.05 in experiments 1 and 2, respectively). 3. VIR consistently and significantly (P less than 0.01) decreased fat excretion, improved fat relative retention and increased dietary AMEn. VIR also significantly (P less than 0.01) increased relative retention of dry matter, while it did not affect nitrogen balance. 4. Neither of the variables of performance and utilisation of dietary nutrients was affected by the interactions between VIR and either dietary E:P ratio or energy concentration. It is concluded, therefore, that the effect of VIR in increasing the utilisation of dietary energy does not depend on the above factors. PMID- 1623424 TI - Effect of high concentrations of dietary vitamin E during various age periods on performance, plasma vitamin E and meat stability of broiler chicks at 7 weeks of age. AB - 1. The effect of high concentrations of vitamin E (alpha-tocopheryl acetate) fed during various age periods on the performance and the oxidative stability (thiobarbituric acid [TBA] values) of the drumstick meat of 7-week-old broiler chicks was determined. The basal diets (for the age periods 0 to 3, 3 to 6 and 6 to 7 weeks) contained 60 g soyabean oil and 24 mg vitamin E/kg. The following five treatments were evaluated: (1) the basal diets from 0 to 7 weeks of age (control); (2) vitamin E, 100 mg/kg diet from 0 to 7 weeks of age; (3) vitamin E, 150 mg/kg diet from 0 to 3 weeks of age; (4) vitamin E, 150 mg/kg diet from 0 to 3 weeks of age and 100 mg/kg diet from 6 to 7 weeks of age; (5) vitamin E, 100 mg/kg diet from 5 to 7 weeks of age. 2. Food intake, weight gain and food efficiency were not significantly (P greater than 0.05) affected by the vitamin E treatments. 3. Plasma alpha-tocopherol (AT) concentrations in treatments 2, 4 and 5 were similar, and markedly higher than those in treatments 1 and 3, while those of treatment 3 were significantly (P less than 0.001) higher than those of treatment 1. Plasma retinol concentrations were not significantly (P greater than 0.05) affected by the vitamin E treatments. 4. TBA values of the meat were very low and not significantly affected by the vitamin E treatments. However, after incubation the TBA values were highly significantly (P less than 0.01) negatively correlated with the amount of vitamin E consumed during the experiment. The stability of meat of birds fed the various combinations of vitamin E (treatments 3, 4 and 5) was significantly (P less than 0.05) higher than that of birds which did not receive additional vitamin E (treatment 1), but it was significantly (P less than 0.001) lower than that of birds which received vitamin E continuously (treatment 2). 5. It is concluded that a high concentration of vitamin E fed during 0 to 3 weeks of age may significantly improve AT status of the broiler chick up to 7 weeks of age. PMID- 1623426 TI - The effect of increasing photoperiod and food restriction in sexed broiler-type birds. I. Growth and abdominal fat cellularity. AB - 1. Sexed broiler-type chicks were raised either under a continuous (CON) 23 h Light (L) and 1 h Dark (D) schedule or an increasing photoperiod (INC) consisting of an initial 6 h L and 18 h D which increased by 4 h L per week from 14 to 35 d of age after which a 23 L:1D was maintained to 49 d of age. 2. From 5 to 11 d of age birds were fed either: ad libitum (AL), energy intake (kJ ME) restricted to 9.414 x gBW0.67 (R1) or energy intake (kJ ME) restricted to 6.276 x gBW0.67 (R2). Food intake was ad libitum at all other times. 3. Food restriction reduced growth to 49 d of age although some compensatory growth did occur. Food efficiency was not significantly affected by restriction. 4. Although abdominal fat pad weight was significantly reduced for R2 compared to AL, this was not significant on a percentage body weight basis. 5. Adipocyte number in the abdominal fat pad was similar for AL, R1 and R2, but concomitant with a smaller fat pad weight, R2 showed reduced adipocyte volume compared to AL. 6. INC birds were lighter at 21 d of age, but body weights were equivalent to CON by 42 d of age. 7. Abdominal fat pad weight was some 10% larger at 49 d of age for INC birds. Adipocyte volume was unaffected, the increase in adipocyte being entirely caused by an increase in adipocyte number in INC birds. PMID- 1623425 TI - Follicle stimulating hormone increases serum oestradiol-17 beta concentrations, number of growing follicles and yolk deposition in aging hens (Gallus gallus domesticus) with decreased egg production. AB - 1. The aims of this study were to determine if the number of small yellow follicles (SYF) and large white follicles (LWF) in ovaries of young and old hens differed; and if injection of old hens with follicle stimulating hormone (FSH) changed growth of and yolk deposition into follicles of old hens. 2. Ovaries were removed and follicles were divided according to size and condition and counted. The number of normal SYF and LWF was decreased in old hens compared to young hens, whereas the number of atretic follicles was greater in old hens compared to young hens. 3. Old hens were injected subcutaneously with saline containing 0.1% bovine serum albumin (BSA, vehicle) or 12.5, 50, 200, 400 micrograms porcine (p) FSH or 25 or 50 IU pregnant mare's serum gonadotropin (PMSG) for 5 consecutive days. Blood samples were taken on days 1 and 5 before FSH and PMSG injection and 2 h after FSH and PMSG injection on day 5. Sudan black and Sudan red dyes were injected intravenously on alternative days to monitor yolk deposition into follicles of the hierarchy removed after the fifth day of FSH treatment. 4. Treatment with 200 micrograms pFSH or 25 IU PMSG for 5 d increased serum progesterone (P4) concentrations as compared to controls. Injection of hens with FSH caused a linear dose dependent increase in serum oestradiol-17 beta (E2) concentrations, dose dependent increase in SYF and LWF, and dose related decrease in number of atretic SYF and LWF. The hierarchy of the ovary was disrupted with PMSG, but not FSH. Larger doses of FSH increased the number of small follicles (10 mm diameter) and yolk deposition. 5. We conclude that small follicles which have not entered the rapid growth phase are responsive to FSH. The increased yolk deposition following FSH treatment may have been a direct effect of FSH or may have been caused by the elevation of serum E2 concentrations in response to FSH treatment. It is possible that old chickens may produce inadequate amounts of FSH which result in decreased rate of follicular growth and ultimately decreased egg production. PMID- 1623427 TI - The effect of increasing photoperiod and food restriction in sexed, broiler-type birds. II. Plasma thyroxine, triiodothyronine, insulin-like growth factor-I and insulin. AB - 1. Sexed broiler-type chicks were raised either under a continuous (CON) 23 h light (L) and 1 h dark (D) schedule or an increasing photoperiod (INC). From 5 to 11 d of age birds were fed either: ad libitum (AL), energy intake (kJ ME) restricted to 9.414 x gBW0.67 (R1) or energy intake (kJ ME) restricted to 6.276 x gBW0.67 (R2). 2. Blood samples were taken at 4, 7, 11, 14 d of age and weekly thereafter to 49 d of age. Plasma thyroxine (T4), triiodothyronine (T3), insulin like growth factor-I (IGF-I) and insulin were determined. 3. CON birds had elevated plasma T3 concentrations to 21 d of age, and greater plasma T4 concentrations at 11 and 21 d of age concurrent with greater food intake. Elevated plasma T3 concentrations in INC birds at 28 d of age coincided with lower plasma IGF-I concentrations at a time when growth and food intake were greater than CON birds. 4. Food restriction elevated plasma insulin and T4 but depressed plasma T3 and IGF-I. Plasma T3 was greater for food-restricted birds at 21 d of age, but subsequently, was generally lower than ad libitum-fed birds which may account for a lack of complete 'catch-up' in growth. 5. Plasma T3 was higher in females at 11 d of age when growth was equivalent for both sexes. From 28 to 42 d, when sex differences in growth became most apparent, plasma T3 was greater in males. PMID- 1623428 TI - Genetic and environmental control of ovarian function in turkeys at sexual maturity. AB - 1. The relationships between the numbers of ovarian yellow follicles and body weight was investigated in four strains of turkeys photostimulated at 24 or 30 weeks of age. The birds were fed ad libitum or control fed to reach 0.8 or 0.6 of the body weight of ad libitum-fed birds at 24 weeks of age. 2. There were more yellow follicles at 24 compared with 30 weeks of age. 3. The number of yellow follicles was higher in bigger strains. 4. Body weight control reduced the number and the proportion of similar sized yellow follicles. The effect decreased with increasing strain body weight. 5. There was a linear relationship of 0.633 between log yellow follicle number and log body weight. The intercept was higher in turkeys photostimulated at 24 compared with 30 weeks of age. PMID- 1623429 TI - Preservation of quail blastoderm cells in liquid nitrogen. AB - 1. Quail blastoderm cells isolated from the yolk were preserved in liquid nitrogen. 2. Frozen-thawed blastoderm cells of the quail were viable and survived in vitro. By injecting the frozen-thawed cells into chick embryos, quail-chick chimaeras were produced. PMID- 1623430 TI - Bilateral testicular asymmetry and supernumerary testes in the domestic fowl (Gallus domesticus). AB - 1. The left and right testis weights from 378 males in 7 experiments were recorded. 2. The relationship between the right and left testis weights was similar in males of different ages, strains and body weights. 3. The left as a proportion of total testes weight was approximately normally distributed about a mean of 0.515. 4. The left testis was greater than the right testis weight in 0.67 of males. 5. The linear regression of the natural logarithm of the right on that of the left testis weights was -0.04 + 0.99X (r2 = 0.98) and it was concluded that, in general, the left and right testes were of similar weight. 6. Three cases of triorchidism (two left testes) occurred, suggesting that this may not be a rare condition in the domestic fowl. PMID- 1623431 TI - The role of radical prostatectomy in the treatment of prostate cancer. AB - Recent advances in our understanding of the surgical anatomy of the prostate have led to an improved operative technique for radical prostatectomy. This technique achieves excellent results in terms of urinary continence and preservation of sexual function without compromising cancer control. It is therefore reasonable to offer radical prostatectomy for the cure of localized prostate cancer to patients who are otherwise well and have a life expectancy of more than 10 years. PMID- 1623432 TI - Prostate cancer: evaluation and radiotherapeutic management. PMID- 1623434 TI - The Regulated Health Professions Act. The keynote address to the Operating Room Nurses Association of Ontario. PMID- 1623433 TI - Neurofibromatoses. PMID- 1623435 TI - Value, venture, vision (keynote address). PMID- 1623436 TI - Sharing power: the Healthy Hospital project. PMID- 1623437 TI - Questions on sterile technique can lead to study and research. PMID- 1623438 TI - Principles of aseptic technique. PMID- 1623439 TI - Development of an operating room nursing workload measurement system. PMID- 1623441 TI - Life-style and dietary factors early and late in Parkinson's disease. AB - The study investigated features of life-style and dietary habits early and late in life of patients with idiopathic Parkinson's disease (IPD). Seventy-one patients and 103 controls were interviewed personally with a structured questionnaire. Living in villages during primary school time was significantly more frequent among patients, and in the urban environment patients had lived less frequently in larger-sized towns. Mushroom harvesting during childhood was more frequent among patients. No difference between patients and controls was found in childhood water supply, habits of fishing in the countryside or at the seaside, and eating such fish. Actual food preference in patients was greater for almonds and plums, while no difference was found in the actual intake of mushrooms, peanuts, oil-dressed salad, fish and animal offals. The study did not indicate a higher consumption of foods known to harbour heavy metals and pesticides in IPD patients either long before or during the disease. Reduced consumption of foodstuffs rich in vitamin E, as reported previously for premorbid patients, is no longer observed in patients with overt disease. PMID- 1623440 TI - Neuropsychological and glucose metabolic profiles in asymmetric Parkinson's disease. AB - Patients with predominantly unilateral parkinsonian signs may provide a unique opportunity to evaluate the cerebral representation of cognitive functions characteristically affected in idiopathic Parkinson's disease. Twenty hemiparkinsonian patients (ten left and ten right) and 10 healthy controls, matched for age and education, were studied with neuropsychological tests and positron emission tomography. Both right and left hemiparkinsonians evidenced impairments in visuospatial and verbal episodic memory function, but had no deficits in executive abilities, compared to controls. None of the neuropsychological test scores distinguished right from left hemiparkinsonians. Glucose metabolic profiles were identical for the three groups in all cortical areas assessed; in the subcortex however, lenticular hypermetabolism contralateral to the predominant side of motor involvement was evident in the left hemiparkinsonian group. Correlational analysis revealed that higher glucose metabolic rates in the basal ganglia of these hemiparkinsonians were associated with lower visuospatial test scores. In frontal and parietal cortex, decreasing glucose metabolism was positively associated with neurobehavioral function; in temporal cortex, measures of attention and memory decreased with increasing glucose metabolic rates. PMID- 1623442 TI - Forearm P-31 nuclear magnetic resonance spectroscopy studies in oculopharyngeal muscular dystrophy. AB - Five siblings with autosomal dominant oculopharyngeal muscular dystrophy (OPMD) underwent P-31 Nuclear Magnetic Resonance Spectroscopy studies of forearm flexor muscles. Mean values of PCr/(PCr+Pi) in the patients were reduced (p = 0.01) and pH elevated (p = 0.02) in resting muscle when compared to controls. During exercise PCr/PCr+Pi) fell quickly to values less than controls (p less than 0.0001) despite submaximal exercise output and developed exercise-induced acidosis which exceeded that of controls (p = 0.05). Acidosis recovered slowly despite relatively normal recovery of PCr/(PCr+Pi) following exercise. Within the patient group, however, one member had normal resting, exercise and recovery values. The studies suggest that OPMD is a more widespread disorder of striated muscle than clinically appreciated. The pattern of findings observed in OPMD differs from those identified in denervation, disuse and mitochondrial myopathy. PMID- 1623443 TI - Diagnosis and management of spinal epidural abscess. AB - Twenty-five patients with spinal epidural abscess were treated at the University of Western Ontario hospitals between July 1980 and July 1990. There were eighteen males (72%) and seven females (28%), with a median age of 60 years. Concurrent illness resulting in immunocompromise was present in 60%. Eleven presented with complete myelopathy, thirteen had limb weakness, and one had no neurological deficit. In twenty cases the abscess consisted of frankly purulent material, while in five the epidural collection consisted of chronic granulation tissue. Staphylococcus aureus was isolated in 64% of the abscesses. Twenty-seven surgical procedures were performed on 21 patients. Ten cases occurred in the cervical spine (40%), seven in the thoracic spine (28%), three in both the cervical and thoracic spine (12%) and five in the lumbosacral spine (20%). Fourteen patients (56%) retained or recovered ambulation and there were five deaths (20%). The progression from back and radicular pain to weakness and eventual paralysis continues to be characteristic of spinal epidural infection. Morbidity and mortality remain unacceptably high because of delay in diagnosis and treatment. Magnetic resonance imaging is the radiological investigation of choice for the diagnosis of spinal epidural abscess. Prompt intervention, before the development of severe neurological deficits, can improve outcome. Immediate surgical drainage combined with antibiotics remains the treatment of choice. PMID- 1623444 TI - Intrathecal baclofen for intractable spinal spasticity--a double-blind cross-over comparison with placebo in 6 patients. AB - A group of six subjects with intractable spinal spasticity completed a double blind cross-over paradigm in which they received two intrathecal bolus injections of baclofen solution five hours apart on two different days and two intrathecal bolus injections of placebo saline five hours apart on two other days. Each subject was repeatedly tested with a battery of clinical and physiological tests. In contrast to the placebo injections, the group responded to the baclofen injections with subjective and objective, clinically significant improvement in parameters of spasticity in their lower limbs, including muscle tone, frequency of spasms, hyperreflexia and passive range of joint motion. Furthermore, this improvement was maintained following thirty consecutive days of intrathecal bolus injections of baclofen at a fixed dose. PMID- 1623445 TI - Fracture of temporal bone with exsanguination: pathology and mechanism. AB - Eight cases of basal skull fracture with transverse fracture of the petrous temporal bone with medial extension to the internal carotid artery and lateral extension of the structures of the middle ear are described. Injuries in all cases were due to major blunt impact to the head usually occurring in a motor vehicle accident. General autopsy revealed major blood loss without any obvious external or internal site of hemorrhage suggesting that exsanguination was a complication of the head injury. The internal carotid arteries at the most medial extension of the fractures were lacerated or transected in all cases. In selected cases, the cervical internal carotid arteries were perfused and perfusate escaped rapidly from the ear(s) with the majority of fluid bypassing the cerebral venous system. Magnetic resonance image reconstruction of sequential sections of the fractured base of the skull confirmed the laceration of the internal carotid arteries and disruption of the middle ear. Based on this evidence, we propose that some displaced fractures of the base of the skull produce carotid-middle ear continuities which act as arterial shunts, resulting in rapid fatal exsanguination through the ear. PMID- 1623446 TI - The anticonvulsant effects of vitamin E: a further evaluation. AB - Vitamin E (d-alpha-tocopherol) has proven to be a useful adjunct to anticonvulsant drugs in clinical studies. Improvement has occurred even in patients with complex partial seizures, which are often resistant to drug therapy. In animals, vitamin E is effective against ferrous chloride seizures, hyperbaric oxygen seizures and penicillin-induced seizures. It has failed, however, to show anticonvulsant effects in the standard animal models used for drug screening--the maximal electroshock and threshold pentylenetetrazol tests. The present experiments were designed to further explore the anti-epileptic actions of vitamin E in animals. Three models related to complex partial epilepsy were used: 1) the development of amygdala-kindled seizures; 2) the development of electrically-induced status in kindled animals; and 3) the development of kainic acid seizures. Vitamin E failed to produce significant effects in any of the models. PMID- 1623447 TI - The pharmacology of chewable versus regular carbamazepine in chronically treated children with epilepsy. AB - We report the first comparison of Chewable and Regular Carbamazepine (CBZ) tablets in children with epilepsy. Forty-four children receiving chronic monotherapy CBZ participated. In month 1 children received regular CBZ; in month 2, the same dose of Chewable CBZ. Once per week fasting predose CBZ and CBZ epoxide serum levels were determined. In a subset of 15 children, at the end of each month serum levels were obtained every 2 hours for 12 hours beginning pre dose. Standards for CBZ and CBZ epoxide were tested in each centre. Overall, weekly levels showed no consistent differences between the month on chewable CBZ and regular CBZ. Seizure control and rates of reported side effects were similar. In five patients chewable CBZ produced higher peak CBZ levels while five had higher peaks with regular CBZ. In conclusion, regular and chewable CBZ often have unpredictable differences in peak but not trough levels of CBZ suggesting that peak level side effects with one form of CBZ might be alleviated by changing to the other. PMID- 1623448 TI - The insular cortex and the pathophysiology of stroke-induced cardiac changes. AB - Over the past fifty years considerable clinical evidence has accrued to demonstrate involvement of the cerebral cortex in cardiac function. Hemispheric stroke is often associated with electrocardiographic (ECG) evidence of cardiac repolarisation abnormalities. In addition strokes of all types are associated with specific pathological changes in the ventricular myocardium (myocytolysis). These effects are not attributable to concomitant cardiac ischemic disease in the majority of cases. The insular cortex has recently been shown to contain a site of cardiac representation. Prolonged stimulation of this region in the rat produces ECG and cardiac pathological changes similar to those observed after human stroke. It is suggested that middle cerebral artery stroke in certain cases either directly or indirectly leads to insular disinhibition, and increased autonomic activity represented by cardiac changes which significantly influence prognosis. PMID- 1623449 TI - Photon radiosurgery: a clinical review. AB - The term radiosurgery has been used to describe a variety of radiotherapy techniques which deliver high doses of radiation to small, stereotactically defined intracranial targets in such a way that the dose fall-off outside the targeted volume is very sharp. Proton, charged particle, gamma unit, and linear accelerator-based techniques appear to be equivalent from the standpoint of accuracy, dose distributions, and clinical results. However, capital and operating costs associated with the use of linear accelerators in general clinical use are much lower. Radiosurgery has an established role in the treatment of arteriovenous malformations and acoustic neurinomas. Interest in these techniques is increasing in neurosurgical and radiation oncological communities, as radiosurgery is rapidly assuming a place in the management of several other conditions, including craniopharyngiomas, meningiomas, and selected malignant lesions. PMID- 1623450 TI - Cerebral aneurysms and polycystic kidney disease: a critical review. AB - The pathogenic basis of the association between adult polycystic kidney disease (APKD) and cerebral aneurysms is unknown. We have compared cerebral aneurysms in 79 patients with APKD gleaned from the literature to the sporadic aneurysm cases reported by the Cooperative Study to determine if there are significant biological differences between these two groups. Sixty-eight patients had a single aneurysm and 11 (14%) had multiple aneurysms. In APKD patients with subarachnoid hemorrhage from a single aneurysm there was a significant over representation of males (72%, p less than 0.01); and the APKD group had more aneurysms of the middle cerebral artery (37%, p less than 0.05). The peak decennial incidence and mean age of rupture of APKD-associated aneurysms was younger (mean age 39.7 years, p less than 0.01) and over 77% of APKD-associated aneurysms had ruptured by age 50 versus 42% for sporadic aneurysms (p less than 0.001). Cerebral aneurysms co-existed with APKD in the absence of hypertension in 25% of 45 cases where the presence or absence of hypertension was recorded. These biological differences and the occurrence of aneurysms in normotensive APKD patients suggests an etiology which may be independent of hypertension and that APKD-associated aneurysms may be genetically determined. It is hypothesized that cases of inherited, familial cerebral aneurysms could be linked to a genetic defect resembling that which occurs on chromosome 16 in APKD. PMID- 1623451 TI - Clinically non-functioning human pituitary adenomas. AB - Clinically non-functioning pituitary adenomas are morphologically classified into two groups, those which have hormone immunoreactivity and ultrastructural features of known adenohypophysial cell types but are clinically silent, and those composed of cells that do not resemble nontumorous adenohypophysial cell types. Among the former are the silent somatotroph adenomas, silent corticotroph adenomas and silent gonadotroph adenomas; the latter include the silent type III adenomas, null cell adenomas and oncocytomas. We review their histological, immunohistochemical and ultrastructural features, the results of in situ hybridization to determine hormone synthesis by these tumors and data obtained from tissue culture characterizing their hormone release in vitro. Non functioning adenomas represent a heterogeneous group. The discrepancies between morphology, immunoreactivity and lack of endocrine activity of silent adenomas are not clear. Oncocytomas are variants of null cell adenomas. We suggest that null cell adenomas and oncocytomas originate in uncommitted pluripotent precursor cells capable of undergoing multidirectional differentiation. The progenitor cells differentiate most frequently toward FSH/alpha-subunit producing cells; the mechanism of preferential differentiation is obscure. PMID- 1623452 TI - Tegmental pontine hemorrhages: clinical features and prognostic factors. AB - We report six patients with partial, predominantly paramedian, tegmental pontine hemorrhages. Constant clinical manifestations consisted of: ipsilateral miosis, horizontal gaze paresis, lower motor neuron facial paresis, contralateral hemisensory loss and mild and transitory hemiparesis, dysarthria and mild or no compromise of consciousness. Five out of six were hypertensive. All patients survived with mild sequelae, oculomotor disturbances being the most persistent deficit. We found in our patients that a transverse diameter of less than 17 mm, unilaterality of the injury and absence of coma were the major indicators of a favorable outcome. PMID- 1623453 TI - Chronic lymphocytic leukemia presenting as a pituitary mass lesion. AB - We describe a unique case of chronic lymphocytic leukemia (CLL) in a patient who presented with bitemporal hemianopsia, adrenal insufficiency, and gonadotrophin deficiency. Studies revealed an enhancing intrasellar mass with suprasellar extension and displacement of the optic chiasm. Peripheral blood and cerebrospinal fluid (CSF) studies disclosed a monoclonal IgM kappa expressing B cell CLL. Biopsy of the pituitary mass revealed dense infiltration of the pituitary gland by leukemic cells. This is, to our knowledge, the first reported case of CLL presenting as a pituitary mass lesion. PMID- 1623454 TI - Neuroblastoma and fetal exposure to phenytoin in a child without dysmorphic features. AB - Despite the fact that the teratogenic effects of phenytoin have been suggested in several case reports, the evidence for a possible oncogenic potential of phenytoin has not been widely recognized. Recently, neuroblastoma as well as other neuroectodermal and non-ectodermal tumors has been seen in several children exposed to phenytoin prenatally. Previous cases have been almost uniformly associated with the features of "fetal hydantoin syndrome" and none have been developmentally normal. We report a developmentally-normal boy of 21/2 years with an abdominal neuroblastoma whose mother had been on phenytoin (as well as carbamazepine) throughout gestation. We review the various neoplasms which have been reported in the offspring of mothers receiving phenytoin. PMID- 1623455 TI - Amantadine treatment for refractory pain and fatigue in patients with multiple sclerosis. PMID- 1623457 TI - Canadian Medicare: view from Utopia. PMID- 1623456 TI - Justifying the procedure. PMID- 1623458 TI - A survey of resuscitation training in Canadian undergraduate medical programs. PMID- 1623459 TI - A survey of resuscitation training in Canadian undergraduate medical programs. PMID- 1623460 TI - Women can abuse too. PMID- 1623461 TI - Reproductive hazards and the workplace. PMID- 1623462 TI - Quality of care: 2. Quality of care studies and their consequences. Health Services Research Group. PMID- 1623463 TI - How to diagnose and treat Lyme disease in children. Infectious Diseases and Immunization Committee, Canadian Paediatric Society. PMID- 1623464 TI - Smoking and caffeine and alcohol intake during pregnancy in a northern population: effect on fetal growth. AB - OBJECTIVES: To assess the prevalence of smoking and of caffeine and alcohol intake during pregnancy in a northern population and to determine the relation of these factors to birth weight, length and head circumference. DESIGN: Questionnaire survey and collection of maternal and newborn measurements. SETTING: Ten communities in the Inuvik Zone, NWT. PATIENTS: A total of 162 women (56 Inuit, 38 Indian, 37 white and 31 mixed race) who presented for prenatal care in their community and gave birth in Inuvik between September 1987 and January 1990 and their newborns. RESULTS: In all, 64% (101/159) of the women smoked, 57% (88/154) ingested more than 300 mg of caffeine daily, and 34% (50/145) drank alcohol during their pregnancy. Smoking, caffeine intake and binge drinking were most frequent among the Inuit and Indian mothers. Smoking was significantly associated with decreased birth weight (p less than 0.001) and length (p less than 0.05). Alcohol intake, especially binge drinking, was significantly associated with decreased head circumference (p less than 0.05). Caffeine was found not to be related to any of the outcome variables after smoking was controlled for through stepwise multiple regression. CONCLUSIONS: The marked prevalence of smoking and alcohol intake during pregnancy and their effects on the newborn are public health concerns in the Northwest Territories and warrant intensive countermeasures. PMID- 1623466 TI - Atherosclerosis and aging of the arterial wall. PMID- 1623465 TI - Cardiac arrest in Ontario: circumstances, community response, role of prehospital defibrillation and predictors of survival. AB - OBJECTIVES: To describe the patient characteristics, circumstances and community response in cases of out-of-hospital cardiac arrest; to evaluate the effect on survival of the introduction of prehospital defibrillation; and to identify factors that predict survival. DESIGN: Population-based before-and-after clinical trial. SETTING: Five Ontario communities: London, Sudbury, the Greater Niagara region, Kingston and Ottawa. PATIENTS: A consecutive sample of 1510 primary cardiac arrest patients who were transported to hospital by ambulance over 2 years. INTERVENTION: The use of defibrillators by ambulance attendants. MAIN OUTCOME MEASURES: Patient characteristics (sex and age), circumstances of arrest (place, whether arrest was witnessed and cardiac rhythm), citizen response (whether cardiopulmonary resuscitation [CPR] was started by a bystander, time to access to emergency medical services and time to initiation of CPR), emergency medical services response (ambulance response time, time to initiation of CPR and time to rhythm analysis with defibrillator) and survival rates. MAIN RESULTS: A total of 92.1% of the patients were 50 years of age or older, and 68.3% were men. Overall, 79.6% of the arrests occurred in the home. The average ambulance response time for witnessed cases was 7.8 minutes. The overall survival rate was 2.5%. The survival rates before and after defibrillators were introduced were similar, and the general functional outcome of the survivors did not differ significantly between the two phases. Factors predicting survival included patient's age, ambulance response time and whether CPR was started before the ambulance arrived. CONCLUSIONS: The survival rate was lower than expected. The availability of prehospital defibrillation did not affect survival. To improve survival rates after cardiac arrest ambulance response times must be reduced and the frequency of bystander-initiated CPR increased. Once these changes are in place a beneficial effect from advanced manoeuvres such as prehospital defibrillation may be seen. PMID- 1623467 TI - Consultations then and now. 1963. PMID- 1623468 TI - Turning sickness into art: Robert Pope and his battle with cancer. PMID- 1623469 TI - Medicare turns 30. PMID- 1623470 TI - Ethics "inherently and inevitably" a part of every medical decision, forum told. PMID- 1623471 TI - Sudden death caused by work-related stress one cost of Japan's trade success. PMID- 1623472 TI - Adenocarcinoma of the gastric cardia. Recurrence and survival after resection. AB - Between January 1, 1983, and December 31, 1988, operations were performed on 112 patients with adenocarcinoma of the gastric cardia. Resection of the primary tumor was performed in 93 patients. For these 93 patients, follow-up until July 1, 1989, averaged 24 months, during which time 59 patients died. Positive resection margins carried a greater risk for the development of a local recurrence but did not correlate with survival. The cumulative overall 5-year actuarial recurrence rate was 69%. The cumulative 5-year recurrence rate for metastases was 64% and for locoregional recurrence it was 36%. The overall 5-year survival rate was 24%. Differences in survival were observed between patients with carcinomas of the various subgroups of the 1987 TNM classification system (T1-T2 versus T3-T4, N0 versus N1-N2, M0 versus M1, Stages I-II versus Stages III IV, Grades 1-2 versus Grades 3-4). In particular, lymph node status as correlated with histopathologic grade showed remarkable differences in survival: patients with no positive lymph nodes in the resection specimen and a Grade 1 or 2 tumor had a significantly better 5-year survival rate (53%) than the other subgroups (N0/Grades 3-4: 21%; N1-N2/Grades 1-2: 12%; N1-N2/Grades 3-4: 14%). PMID- 1623473 TI - Primary colorectal lymphoma in Taiwan. AB - BACKGROUND: Sixteen patients with primary lymphoma of the colon and rectum were studied. METHODS: The median age of these patients was 34 years, and 13 were men. These patients often experienced abdominal pain, diarrhea, a palpable abdominal mass, weight loss, bloody stools, and tumor of the cecum. Intermediate or high grade lymphomas occurred in 14 patients, and 5 patients had T-cell lesions. The diagnoses were established by using laparotomy in 14 patients and colonoscopic biopsy in 2 patients. Fourteen patients had surgical resections followed by chemotherapy: cyclophosphamide, doxorubicin, vincristine, and prednisolone in 10; cyclophosphamide, vincristine, and prednisolone (COP) in 2; and cyclophosphamide, vincristine, methotrexate, and prednisolone in 1 patient. Two patients underwent biopsy alone followed by chemotherapy with COP in one and chemotherapy with prednisolone in the other. RESULTS: The median follow-up time was 38 months (range, 2-82 months). Eight patients are alive with no evidence of disease (range, 10-82+ months). Six patients died of disease from 2 to 44 months after diagnosis. One patient who had no evidence of lymphoma died of esophageal carcinoma at 61 months. The median survival time was 59 months. CONCLUSIONS: The authors' experience with colorectal lymphoma in Taiwan is different from that reported from Japan and other countries. The patients of this study were significantly younger and many had T-cell lesions. Despite the frequently poor histologic types, surgical resection and adjuvant chemotherapy can result in long term, disease-free survival in many patients with primary colorectal lymphoma. PMID- 1623474 TI - Experience with high-dose radiation therapy and the intestinal sling procedure in patients with rectal carcinoma. AB - BACKGROUND: Surgery for Dukes' Stage B2 or C rectal carcinoma has a locoregional recurrence rate of 15-67%; this rate is significantly reduced when postoperative radiation therapy (RT) is given. However, RT contributes to radiation-associated small bowel injury in a dose-dependent manner. METHODS: Polyglycolic acid mesh used as an intestinal sling is able to keep the small bowel out of the pelvis during RT, thereby preventing radiation-associated small bowel injury. RESULTS: The authors reviewed the perioperative experiences and acute toxic effects of RT in 53 patients in whom the polyglycolic sling was placed from May 1985 through May 1990 during laparotomy for rectal malignancies (47 primary and 6 recurrent). There were 26 men and 27 women whose ages ranged from 34 to 88 years (mean, 64.7 years). Mild postoperative ileus occurred in most patients, and one patient had an anastomotic leak with a pelvic abscess. Bowel displacement from RT portals was confirmed using radiologic contrast studies. Forty-three patients with primary tumors have completed postoperative RT, and a mean of 5174 cGy has been administered. CONCLUSIONS: After 1-6 years of follow-up (mean, 2.1 years), eight patients have died of systemic disease. There were no cases of radiation associated small bowel injury and only two cases of pelvic recurrence from primary rectal adenocarcinoma (5%). PMID- 1623475 TI - Giant cell carcinoma of the lung. AB - BACKGROUND: Giant cell carcinoma of the lung has been described as an aggressive tumor characterized by extensive local and distant disease and extremely short survival. In 1981, the World Health Organization defined giant cell carcinoma as a variant of large cell carcinoma. Before then giant cell lung cancer was a descriptive term, but it was not considered a separate entity. METHODS: The authors retrospectively studied 16 cases of giant cell carcinoma of the lung. RESULTS: These cases had a prognosis that was not appreciably different from that for lung cancer of other non-small cell histologic types. Of those patients with pathologic Stage I or II at resection, five of nine are alive and disease-free from 20 to 116 months and one has died without evidence of disease at 15 months. CONCLUSIONS: Based on this series and a review of the literature, there appears to be an increased incidence of both clinical and subclinical gastrointestinal tract involvement in patients with this histology, compared with patients with other non-small cell histologic types. The authors conclude that patients with giant cell carcinoma of the lung have a prognosis similar to that of patients with other non-small cell histologic types, and that clinicians should be aware of the increased incidence of gastrointestinal tract involvement in this disease. PMID- 1623476 TI - International trends in the incidence of bone cancer are not related to drinking water fluoridation. AB - BACKGROUND: Because osteosarcomas may develop in rats exposed to fluoridated water, water fluoridation might pose a cancer risk to humans. METHODS: A time trend analysis of the cumulative risk (CR) of bone cancer for the period 1958 1987 for 40 cancer registry areas showed an increased risk for young males in Canada, Europe, and the United States, and a decreased lifetime risk for either sex in Europe. RESULTS: This was unrelated to water fluoridation and may have resulted from changes in coding practices. Bone cancer risk was inversely related to the incidence of cancers of unknown origin, suggesting that bone metastases were erroneously coded as primary bone cancer. In 1968-1972, most areas recorded more bone cancer deaths than new cases of the disease. CONCLUSIONS: The mortality/incidence ratio, but not the incidence rate (IR), has dropped sharply since then, which erodes the basis of past inferences relating cancer mortality to fluoridation. PMID- 1623477 TI - Relationship between chronic lymphocytic leukemia and small lymphocytic lymphoma. A comparative study of membrane phenotypes in 270 cases. AB - BACKGROUND: Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are considered different tissue expressions of the same disease process, although they are clinically separable nosologic entities. A systematic comparison of the membrane phenotypes in the two entities needs to be investigated. METHODS: Cell suspensions from peripheral blood of 184 patients with CLL, bone marrow from 23 patients with CLL, and lymph nodes from 86 patients with SLL were analyzed to compare the membrane phenotypes. RESULTS: There were no significant differences between the three groups in the mean percentages of cells expressing surface immunoglobulin (SIg), CD5, CD19, CD20, and CD2 or in the frequency of cases with weak SIg. Although the mean percentage of mouse rosette forming cells (MRFC) showed no statistical difference between bone marrow from CLL and lymph nodes from SLL, the mean percentage of MRFC in peripheral blood from CLL (48.02 +/- 18.23%) was twice as high as that in bone marrow from CLL (25.27 +/- 21.51%) and lymph nodes from SLL (20.87 +/- 16.72%) (P less than 0.001). Correlation analysis assessing the association of MRFC and residual T cells showed a negative coefficient (r), and the r was statistically significant in bone marrow from CLL and lymph nodes from SLL but not in peripheral blood from CLL. The mean CD4/CD8 ratios in descending order were as follows: the ratio in lymph nodes from SLL (4.25) was greater than that in peripheral blood from CLL (1.70), which was greater than that in bone marrow from CLL (0.82); this followed the same pattern as the respective tissue controls. The mean ratios were not statistically different from those of their respective control groups. CONCLUSIONS: The similarity of membrane phenotypes between CLL and SLL provided evidence that the two are different tissue expressions of the same disease. The alterations in CD4/CD8 ratios were related to the type of tissue analyzed and not to the disease process. The difference in MRFC presumably results from the microenvironment or residual T-cells. PMID- 1623478 TI - Expression of disialogangliosides GD2 and GD3 on human soft tissue sarcomas. AB - METHODS: Fifty-six freshly frozen human sarcomas were studied for expression of disialogangliosides by avidin-biotin immunohistochemical staining with purified monoclonal antibodies (MoAb) 3F8 (antidisialoganglioside GD2) and R24 (antidisialoganglioside GD3). RESULTS: Ninety-three percent of the tumors tested by the immunohistochemical staining expressed GD2 and 88% expressed GD3. The intensity of expression varied among sarcomas of different histologic types. Liposarcoma, fibrosarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and spindle cell sarcoma reacted strongly with 3F8 and R24. Embryonal rhabdomyosarcoma and synovial sarcoma demonstrated substantially weaker staining by either MoAb. Weakly reactive or nonreactive tumors were, in general, high grade or metastatic sarcomas. Ganglioside extraction and thin-layer chromatography/immunothin-layer chromatography of two liposarcomas confirmed the identities of these gangliosides. CONCLUSIONS: GD2 and GD3 may indicate sites for MoAb-targeted imaging and therapy for sarcomas. The association of a diminished stainability by 3F8 and R24 with aggressive sarcomas may indicate prognostic significance. PMID- 1623479 TI - Results of surgical treatment of 1028 cervical cancers studied with volumetry. AB - BACKGROUND AND METHODS: The clinical staging system of cervical cancer according to the International Federation of Gynecology and Obstetrics (FIGO) entails a large measure of subjectivity. This study analyzed the results of 1028 patients with cervical cancer at three reference centers. All patients had radical surgery, and all surgical specimens were processed as histologic giant sections with precise volumetry of the tumor. RESULTS: The interpretation of the histologic findings of parametrial invasion, vascular involvement, and lymph node involvement was found to differ somewhat among the three centers. However, all these findings were associated with tumor size. Survival rates correlated more consistently with tumor volume than with clinical or histologic stage. Five-year survival rates ranged from 91% for patients with tumors smaller than 2.5 cm3 to 70% for those with tumors 10-50 cm3. The 5-year survival rate of 24 patients with tumors larger than 50 cm3 (71% of whom had lymph nodes with positive findings) was 48%. Survival rates were identical among the three centers for patients with tumors smaller than 10 cm3, despite different degrees of surgical radicality. In contrast, more radical surgery was associated with significantly better survival rates in patients with larger tumors. CONCLUSIONS: The results of this study indicate that volumetry of the tumor permits a more accurate assessment of therapeutic results in patients with cervical cancer than does the FIGO classification. Pretherapeutic assessment of tumor volume is possible with magnetic resonance imaging. It seems that maximum parametrial resection is not necessary for patients with smaller tumors (smaller than 10 cm3), but truly radical surgery in patients with bulky tumors achieves better results than those usually expected in Stage IIb cervical cancer and at least comparable to those of radiation therapy. PMID- 1623480 TI - Disseminated intravascular coagulation and excessive fibrinolysis in a patient with metastatic prostate cancer. Response to epsilon-aminocaproic acid. AB - BACKGROUND: Disseminated intravascular coagulation (DIC) and primary fibrinolysis have both been reported in association with prostate carcinoma. The correct diagnosis of the coagulopathy can be difficult and the appropriate management controversial. METHODS: A case is presented of a man in whom DIC and soft tissue hemorrhage developed after prostatic biopsy. The results of therapy and a review of the literature are discussed. RESULTS: Fibrinogen levels continued to decrease despite high-dose estrogen therapy, but they rapidly returned to normal after therapy with epsilon-aminocaproic acid. Although routine coagulation tests were suggestive of primary fibrinolysis, the results of the D-dimer assay confirmed that the patient had DIC associated with excessive fibrinolysis. CONCLUSION: A review of the literature suggests that most cases of primary fibrinolysis are probably DIC with excessive secondary fibrinolysis. In cases in which bleeding is the primary manifestation of DIC and there is a significant reduction in alpha-2 plasmin inhibitor activity, a trial of epsilon-aminocaproic acid and low-dose heparin should be considered. The failure in this case of estrogen therapy to correct the coagulopathy, despite a later good tumor response, is consistent with the delay in which anorchid testosterone levels are obtained after initiating treatment. PMID- 1623481 TI - Urethral diverticular carcinoma. AB - BACKGROUND: Urethral diverticular carcinoma is an unusual finding in a urologic lesion commonly found in female patients. METHODS: This report presents 6 new cases and reviews the other 53 cases in the English literature. RESULTS: Adenocarcinoma occurs more frequently than transitional and squamous cell cancers combined. CONCLUSION: The prognosis of the former is more favorable. In general, radical therapy is recommended. However, in some instances of localized disease, and with careful follow-up, a more conservative approach might be attempted. PMID- 1623482 TI - Cell kinetics of medulloblastomas. AB - BACKGROUND: Cell kinetics and clinical behavior were correlated for 22 primary and 10 recurrent or metastatic medulloblastomas from 30 patients. METHODS: Twenty six patients received bromodeoxyuridine (BUdR) intravenously during craniotomy; excised specimens were stained by the immunoperoxidase method. The BUdR labeling index (LI) was calculated. Four patients received a pulse of tritiated thymidine; LI was calculated autoradiographically. RESULTS: The mean LI for 32 tumors (11.7 +/- 1.3% standard error) indicated high proliferative potential. LI appeared higher in tumors from younger patients and those in the cerebellar hemisphere as compared with those in the cerebellar vermis. LI did not correlate with survival time. In six BUdR-labeled tumors labeled with iododeoxyuridine, the S-phase duration was 6.1-11.3 hours (mean, 8.0 +/- 0.8 hours); the potential doubling time was 25-82 hours. The actual doubling time, estimated in three cases from serial imaging, was 20-24 days. A cell loss factor of approximately 0.90 was assumed. CONCLUSION: A high LI may reflect rapid medulloblastoma growth, but survival seemed more dependent on sensitivity to radiation therapy. PMID- 1623483 TI - Hand-rolled cigarette smoking and risk of cancer of the mouth, pharynx, and larynx. AB - A case-control study, involving 205 patients with cancer of the mouth, pharynx, and larynx and 273 control subjects with conditions considered not related to tobacco or alcohol consumption, was performed in Montevideo, Uruguay, between January 1988 and December 1990. Smokers of hand-rolled cigarettes showed an increased risk of cancer of the mouth and pharynx (odds ratio [OR] = 2.5; 95% confidence limit = 1.2-5.2) when compared with smokers of manufactured cigarettes. Also, the risk of laryngeal cancer was greater among smokers of hand rolled cigarettes (OR = 2.7; 95% confidence limit = 1.3-5.7) as compared with smokers of commercial cigarettes. PMID- 1623484 TI - Documentation of Burkitt lymphoma with t(8;14) (q24;q32) in X-linked lymphoproliferative disease. AB - BACKGROUND: Acquired hypogammaglobulinemia or agammaglobulinemia, aplastic anemia, chronic or fatal infectious mononucleosis (IM), virus-associated hemophagocytic syndrome, and a variety of B-cell malignant lymphomas (ML) develop in boys with X-linked lymphoproliferative disease (XLP) after infection by the Epstein-Barr virus (EBV). They have an inherited immunodeficiency to EBV. Approximately 80% of the patients die during childhood and 100% by the age of 40. The ML occurring in patients with XLP are different from those of other populations in that there is a maternal family history of males with phenotypes of XLP, particularly ML involving the ileocecal region. METHODS: This article describes two brothers with XLP in whom ML developed. Also, a maternally related male cousin had died of aplastic anemia complicating IM. RESULTS: A Burkitt lymphoma (BL)-specific translocation of t(8;14) (q24;q32) was observed in the BL cells of the younger brother. The histopathologic appearance and rapid relapse after complete remission in the patient also are suggestive of this aggressive phenotype. CONCLUSIONS: This tumor in the patient documents that the BL of patients with XLP probably arises from characteristic tumor-specific chromosomal translocations, as hypothesized in 1980. PMID- 1623485 TI - Pregnancy outcome in survivors of advanced Hodgkin disease. AB - BACKGROUND: Pregnancy outcome was reported by 139 survivors of advanced Hodgkin disease treated on nine protocols of Cancer and Leukemia Group B from 1966 to 1986. METHODS: These patients provided data on 302 singleton pregnancies of a duration of at least 20 weeks that occurred before, during, or after treatment for Hodgkin disease (252, 26, and 24 pregnancies, respectively). RESULTS: There were 4 perinatal deaths, as compared with 5.7 expected. Cancer subsequently developed in 2 offspring (expected, 1.2). However, 22 newborn infants had low a birth weight, exceeding the expected number of 13.7 (relative risk 1.6; 95% confidence interval, 1.0-2.4). The excess number of low weight births occurred primarily during the period of Hodgkin disease diagnosis and treatment but is based on small numbers. CONCLUSION: No increase in adverse outcome occurred in pregnancies that antedated the development of Hodgkin disease. PMID- 1623486 TI - The role of radiation therapy in Hodgkin disease: experience and controversy. The 54th annual Janeway Lecture: 1989. AB - BACKGROUND: Beginning in 1970, a series of patients with Hodgkin disease were treated at the University of Minnesota, after staging laparotomy, with radiation therapy (RT) for Stage I, II, and IIIA Hodgkin disease. This report is an analysis of the results of the treatment and of treatment modifications. METHODS: From 1970 to 1974, all patients were treated with standard RT. In 1975, an analysis of these patients indicated that patients with large mediastinal mass (LMM) and patients with Stage IIIA spleen-positive (IIIAS+) disease had a higher recurrence rates than patients without these factors. Subsequently, a schema of radical radiation therapy (RRT) was devised, which included low-dose lung RT for patients with LMM and low-dose liver RT for patients with IIIAS+ disease. RESULTS: Analysis of the results of the two treatments indicates that the use of low-dose lung RT in patients with LMM and low-dose liver RT in patients with IIIAS+ Hodgkin disease produced survival and recurrence-free survival results equivalent to those achieved by use of combined modality treatment (CMT) or chemotherapy (CT) alone. CONCLUSIONS: The use of RT with whole lung and liver irradiation for patients with LMM and IIIAS+ Hodgkin disease, respectively, produces results that are equivalent to those of CMT or CT alone with the advantage of a decreased incidence of second malignant neoplasms. In addition, patients who do not respond to initial RT have a greater chance of being saved with chemotherapy than do patients initially treated with CMT of being saved with RT. The authors suggest that radical RT is the treatment of choice for patients with LMM and/or IIIAS+ Hodgkin disease. PMID- 1623487 TI - Cytogenetic characteristics of childhood non-Hodgkin lymphoma. AB - Cytogenetic studies were performed successfully on 24 patients with non-Hodgkin lymphoma (NHL) who were younger than 15 years of age. Of these, 22 patients (92%) had abnormal clones. With respect to histologic findings, 3 (25%) of the 12 patients with lymphoblastic lymphoma had 14q11 translocations and 2 (17%) had t(9;17) (q34;q23). Four (80%) of the five patients with small non-cleaved cell lymphoma had t(8;14)(q24;q32). With respect to immunologic findings, four (44%) of the nine patients with T-cell lymphoma had abnormalities consisting of 14q11 and 7q36 translocations, in which the T-cell receptor genes resided. Three (33%) of the patients with T-cell lymphoma had t(9;17)(q34;q23). However, three (43%) of the seven patients with B-cell lymphoma had t(8;14) (q23;q32), and two (29%) of the patients with B-cell lymphoma had an extra i(11q) chromosome with a resultant 11q tetrasomy. Non-T-cell non-B-cell lymphomas, which occurred in 21% of all patients, showed various chromosomal abnormalities. This study demonstrated that, in childhood NHL, karyotype correlates closely with immunophenotype, clinical features, and histologic findings. PMID- 1623488 TI - Digital imaging in dermatology. PMID- 1623489 TI - Digital imaging in dermatology. AB - In this article we discuss the recent surge in activity in digital imaging in dermatology. The key role of digital imaging as an adjunct to detection of early malignant melanoma, with application in following patients with the dysplastic nevus syndrome, is explored. Other current and future uses of digital imaging in image archiving, in clinical studies such as hair growth studies, and in telediagnosis are reviewed. We review the varying research activities of image analysis laboratories participating in the dermatology image researching group. Research laboratories included in this group are at Oregon Health Sciences University, Xerox Corporation, University of Arizona, University of Cincinnati, University of Munich, University of Wurzburg, University of Arkansas, Harvard University, Southern Illinois University-Edwardsville, Johns Hopkins University, National Institutes of Health, and University of Missouri at Columbia and Rolla. The role of new imaging devices in dermatology including the "nevoscope" and the dermatoscope is explored. Goals and challenges for the new technology are discussed. PMID- 1623490 TI - Use of computer graphic images in teaching dermatology. AB - A microcomputer-based system for copying, storing, retrieving, and displaying color still images was assembled from commercially available components. The system was tested against 35-mm color photographic transparencies by measuring the performance of 91 medical students in a task of identifying the primary morphology of eight skin lesion images from the displayed images. There was no significant difference in the students' performance between the two display media. PMID- 1623491 TI - Three-dimensional imaging and reconstruction of skin lesions. AB - An optical instrument called a "nevoscope" is used to image skin lesions by transillumination with visible light. The lesion is transilluminated by a fiber optic annular ring light source that directs light into the skin area surrounding the lesion, forming a virtual source just beneath the lesion. Mirrors uniformly spaced around the lesion and tilted at various angles provide orthographic projections of the skin lesion. Additional views are obtained by rotating the mirror assembly. These multiple views are used in a direct three-dimensional (3D) reconstruction of the lesion using a filtered backprojection method. In this paper, we discuss the methodology of direct 3D reconstruction from 2D views of a transilluminated skin lesion as obtained using the new prototype nevoscope. We present the results of direct 3D reconstruction of a simulated phantom and a test object imaged using the nevoscope. In addition, a skin lesion was scanned in situ using the new prototype nevoscope. Results of the reconstruction of this lesion are also presented. PMID- 1623492 TI - Segmentation of images of skin lesions using color and texture information of surface pigmentation. AB - Image segmentation algorithms extract regions on the basis of similarity of a predefined image feature such as gray-level value. In many applications, images that exhibit a variety of structure or texture cannot be adequately segmented by gray-level values alone. Additional features related to the structure of the image are needed to segment such images. Images of skin lesions exhibit significant variations in color hues as well as geometrical appearance of local surface structure. For example, images of cutaneous malignant melanoma exhibit a rich combination of color and geometrical structure of pigmentation. In these images, the local repetition of the geometrical surface structure provides the basis for the appearance of a texture pattern in the neighborhood region. For obtaining meaningful segmentation of images of skin lesions, a multichannel segmentation algorithm is proposed in this paper which uses both gray-level intensity and texture-based features for region extraction. The intensity-based segmentation is obtained using the modified pyramid-based region extraction algorithm. The texture-based segmentation is obtained by a bilevel shifted-window processing algorithm that uses new generalized co-occurrence matrices. The results of individual segmentations obtained from different channels, representing the complete set of color and texture information, are analyzed using heuristic merging rules to obtain the final color- and texture-based segmentation. Simulated as well as real images of skin lesions, representing various color shades and textures, have been processed. We show that using contrast link information in the pyramid-based region extraction process, and using the absolute magnitude and directional information in the generalized co occurrence matrices (GCM) method, significant improvement in image segmentation can be obtained. Further, by incorporating the merging rules better results are obtained than those obtained using the gray-level intensity feature alone. PMID- 1623493 TI - Texture in skin images: comparison of three methods to determine smoothness. AB - Smooth texture, a critical feature in skin tumor diagnosis, is analyzed using three texture measurement methods. A dermatologist classified 1290 small blocks within 42 tumor images as smooth, partially smooth, or nonsmooth. Texture discriminatory power of three methods were compared: the neighboring gray-level dependence matrix (NGLDM) method of Sun and Wee, the circular symmetric autoregressive random field model of Kashyap and Khotanzad, and a new peak variance method. The texture analysis method that allows best prediction of smoothness for our tumor domain is the NGLDM method, affording 98% correct prediction of a smooth block with 21% false positives. We discuss applicability of texture analysis to dermatology. PMID- 1623494 TI - Automatic detection of asymmetry in skin tumors. AB - Asymmetry, a critical feature in the diagnosis of malignant melanoma, is analyzed using a new algorithm to find a major axis of asymmetry and calculate the degree of asymmetry of the tumor outline. The algorithm provides a new objective definition of asymmetry. A dermatologist classified 86 tumors as symmetric or asymmetric. Borders of tumors were found either manually or automatically using a radial search method. With either method, asymmetry determination by the asymmetry algorithm agreed with the dermatologist's determination of asymmetry in about 93% of cases. PMID- 1623495 TI - Automatic detection of irregular borders in melanoma and other skin tumors. AB - An irregularity index previously developed is applied to detect irregular borders automatically in skin tumor images, particularly malignant melanoma. The irregularity index is used to classify various tumor borders as irregular or regular. This procedure processes tumor images with borders automatically determined by a radial search algorithm previously described. Potential use of this algorithm in an in vivo skin cancer detection system and errors expected in the use of the algorithm are discussed. PMID- 1623496 TI - Automatic registration of multiple skin lesions by use of point pattern matching. AB - Computerized comparison of serial skin images is a potentially valuable tool for melanoma screening. In automating this process, matching or "registering" each lesion in a pair of images plays an important role in looking for clinically significant change. We have investigated three practical techniques--a point pattern correlation, a 2-point geometrical transformation, and a 3-point geometrical transformation--for their effectiveness in matching and identifying lesions in pairs of skin images. These techniques view the spots in each image as a point pattern to be matched from image to image. Each of these methods is shown to be quite effective as long as one or more known initial match points can be provided. Experiments performed by imaging actual patients under realistic conditions indicate that the 3-point transformation algorithm performs the best overall, achieving an average matching accuracy of 97%. The nature of these algorithms, their relative performance under a range of conditions, and possible methods for improving accuracies are discussed. PMID- 1623497 TI - Automatic derivation of initial match points for paired digital images of skin. AB - Computerized matching of skin images has been suggested as a means of screening for changes indicative of malignant melanoma. Matching or "registering" each lesion in a pair of images plays an important role in this process. Point-pattern matching algorithms based upon correlation or geometric transformations of the image pairs have been shown to be effective for this registration but require knowledge of one or more "initial match" points which are known to be the same on both images. A method is described for automatically finding these initial match points with a high degree of success. Our algorithm uses the so-called "Gabriel graph" representation of the paired images to select sets of probable matching points. Performance of the algorithm has been measured in realistic trials, using images of patients with large numbers of pigmented lesions. Results show that the single best match chosen is correct greater than 99% of the time, while over 93% of the first three consecutive matches will be chosen correctly. It is likely that these results can be improved through the use of additional nonpositional information or additional image processing. PMID- 1623499 TI - Current bibliography of cell calcium prepared by the University of Sheffield Biomedical Information Service. PMID- 1623498 TI - An automatic color segmentation algorithm with application to identification of skin tumor borders. AB - A principal components transform algorithm for automatic color segmentation of images is described. This color segmentation algorithm was used to find tumor borders in six different color spaces including the original red, green, and blue (RGB) color space of the digitized image, the intensity/hue/saturation (IHS) transform, the spherical transform, chromaticity coordinates, the CIE transform and the uniform color transform designated CIE-LUV. Five hundred skin tumor images were separated into a training set and a test set for comparison of the different color spaces. Automatic induction was applied to dynamically determine the number of colors for segmentation. Ninety-one percent of image variance was contained in the image component along the principal axis (also containing the most image information). When compared to a luminance radial search method, the principal components color segmentation border method performed equally well by one measure and 10% better by another measure, including more near border points outside the tumor. The spherical transform provides the highest success rate and the chromaticity transform the lowest error rate, although large variances in the data preclude definitive statistical comparisons. PMID- 1623500 TI - Ehrlich tumour cells: Ca(2+)-uptake modification by aluminium lactate. AB - Aluminium lactate provokes the same modification of 45Ca(2+)-uptake by Ehrlich ascites tumour cells as does ferric lactate. The increase of uptake is metal complex concentration-dependent, and in contrast to ferric lactate, is only partially inhibited by albumin. Under the same experimental conditions, chromic lactate provoked no modification of that uptake. A plasma membrane rigidity increase provoked by coordination binding of aluminium to phospholipids is likely to be the main cause of Ca(2+)-uptake modification by aluminium lactate. PMID- 1623501 TI - Spectral characterization of the effect of viscosity on Fura-2 fluorescence: excitation wavelength optimization abolishes the viscosity artifact. AB - A systematic study of the spectral characteristics of the viscosity artifact in Fura-2 based [Ca2+] measurements reveals that, by selecting excitation wavelengths approximately 10 nm longer than those routinely employed and modestly reducing excitation bandpasses, the magnitude of the artifact can be reduced to experimentally undetectable levels without greatly impairing [Ca2+] measurements. The feasibility of this approach was confirmed on a ratio imaging microscope; the magnitude of the artifact observed in dextran-conjugated Fura-2 solutions prepared in water or in 50% sucrose was not statistically significant using an excitation wavelength pair of 361/389 nm, whereas at 350/380 nm [Ca2+] was underestimated by 34% in the higher viscosity solution. Thus, provided potential pitfalls are taken into account, a simple change in imaging protocol can avoid the viscosity artifact without recourse to correction factors. This approach may be employed either routinely, or else merely to test whether apparent [Ca2+]i differences observed at more conventional wavelengths arise from the viscosity artifact. PMID- 1623502 TI - Ionomycin produces an improved volume recovery by an increased efflux of taurine from hypoosmotically stressed molluscan red blood cells. AB - Nucleated erythrocytes of the blood clam, Noetia ponderosa, recover cell volume after a hypoosmotic stress by an efflux of K+, Cl- and taurine. When the cells are exposed to ionomycin followed by hypoosmotic stress, swelling is less and volume recovery is both faster and more complete than in control cells without the ionophore. The improved volume recovery is caused by a large increase in the efflux of taurine. The taurine efflux is altered by changing Ca2+ concentrations in the presence of the ionophore. Potassium regulation by the osmotically stressed erythrocytes is also increased in the presence of ionomycin, but only by a small amount, perhaps accounting for the initial decrease in swelling. Variation of Ca2+ in the presence of ionomycin without osmotic stress produces no change in the regulation of either osmolyte. These results indicate that both the osmotic stress and an increase in [Ca2+]i are required for the permeability change that produces taurine efflux. PMID- 1623503 TI - Trigeminovascular system. PMID- 1623504 TI - Cluster headache. PMID- 1623505 TI - Personality factors in recurring and chronic pain. PMID- 1623506 TI - Activation of the trigeminovascular system by mechanical distension of the superior sagittal sinus in the cat. AB - Distension of dural sinuses in man produces migraine-like pain. In eight alpha chloralose anaesthetized cats mechanical distension of the superior sagittal sinus with a small intraluminal device was used to activate single units in the dorsolateral C2 spinal cord. Units in this region have been shown to respond to electrical stimulation of the superior sagittal sinus in the cat model. Linked responses to mechanical dilatation could only be obtained with very rapid stretching stimuli or high amplitudes of distension of the vessel. Lower thresholds for transduction of distension in the vessel wall may depend on transferral to the dura or biochemical or neural pre-sensitization of the superior sagittal sinus. These data are consistent with the view that migraine is not primarily a vascular disorder but requires at least humoral or neural facilitation. PMID- 1623507 TI - Subcortical cerebral blood flow and metabolic changes elicited by cortical spreading depression in rat. AB - Changes in cerebral cortical perfusion (CBFLDF), local cerebral blood flow (lCBF) and local cerebral glucose utilization (lCGU) elicited by unilateral cortical spreading depression (SD) were monitored and measured in separate groups of rats anesthetized with alpha-chloralose. CBFLDF was recorded with laser Doppler flowmetry, while lCBF and lCGU were measured by the quantitative autoradiographic [14C]iodoantipyrine and [14C]-2-deoxyglucose methods, respectively. SD elicited a wave of hyperemia after a latency of 2 to 3 min followed by an oligemic phase. Ninety minutes following the onset of SD cortical (frontal, parietal and occipital) lCBF and lCGU were essentially the same as on the contralateral side and in sham-treated rats. However, alteration in the lCBF and lCGU in upper and lower brainstem persisted. The present results demonstrate, for the first time, that long-lasting cerebrovascular and metabolic alterations take place within the subcortical regions following SD. These regions provide an attractive site to integrate observations in man concerning spreading depression and the aura of migraine with the other features of the syndrome. PMID- 1623508 TI - Pain sensitivity and pain reactivity of pericranial muscles in migraine and tension-type headache. AB - We investigated whether experimentally determined, suprathreshold pain sensitivity of pericranial musculature in patients with tension-type headache differs from that of migraine patients or from that of healthy subjects. Furthermore, we looked to see whether differences could be found in the effects of experimental pain induction on EMG activity of pericranial musculature and whether subgroups could be discovered with higher and lower pericranial pain sensitivity within the three diagnostic groups in terms of neurophysiological, psychological and clinical variables. In 20 patients with tension-type headache, 23 patients with migraine without aura, and 29 healthy individuals experimental pain was induced in the temporal muscle by mechanical pressure; pain sensitivity in the entire metrically subdivided suprathreshold pain sensitivity range was measured. Surface EMG activity of pericranial muscles was determined before, during and after experimental pain induction. In addition, headache characteristics as well as personality and mood states were determined and recorded in a standardized fashion. There were no significant differences in pain sensitivity of pericranial musculature between the three groups. Patients with tension-type headache showed significantly higher EMG scores during suprathreshold pain stimulation than did migraine patients. EMG scores of healthy subjects fell between these two groups. With respect to pericranial tenderness significant differences in clinical, neurophysiological and psychological variables were found only between subgroups within the group of patients with tension-type headache. The results indicate that significant differences in the examined groups are found not in pain perception but in the processing or reaction to experimental headache stimuli. In patients with tension-type headache subgroups evolve based on pericranial pain sensitivity with quantitatively and/or qualitatively impaired reactions; for this reason diagnostic grouping according to the IHS classification seems to be pathophysiologically relevant. The intraindividual phasic comparison of pain reactions appears to be more important than the absolute interindividual tonic comparison. PMID- 1623509 TI - Tension headache and the cervical spine--plain X-ray findings. AB - The aim of the present study was to investigate if there is any causal connection between plain X-ray findings of the cervical spine and tension headache. We evaluated the X-rays of the cervical spine of 243 patients, in 91 of which the diagnosis was "tension headache", in 102 "headache not fulfilling the criteria of tension headache" and in 50 "spondylogenic complaints without headache". We compared these three groups with regard to frequency and severity of radiologically assessable changes of the cervical spine and found that patients with tension headache had normal findings significantly more often and significantly less often functional or organic changes or both than patients of the other two groups. The radiologically assessable changes of the cervical spine are unlikely to have an essential role in the cause or mechanism of tension headache. PMID- 1623510 TI - Cytochrome P-450-dependent hydroxylation in migraine. AB - The hypothesis was tested that an acute oxidation deficiency related to potential dietary trigger factors plays a role in the migraine attack. Migraine sufferers (14F and 4M), fulfilling the criteria for migraine with and without aura according to the classification of the International Headache Society, were coadministered oral mephenytoin (100 mg) and debrisoquine (10 mg) during the initial phase of a typical migraine attack. This was repeated during a period without migraine. The hydroxylation of mephenytoin and debrisoquine hydroxylation did not differ during and without the migraine attack. We conclude that hydroxylation, via cytochrome P-450 (2D6, 2C8 and 9), is not reduced during the migraine attack. The results do not support the hypothesis that oxidation deficiency is involved in the pathophysiology of migraine. PMID- 1623511 TI - Cytochrome-P450-dependent hydroxylation in cluster headache. AB - Two isozymes of the cytochrome-P450-dependent drug oxidizing system exhibit polymorphism. Five to 10% of a Caucasian population are deficient in debrisoquine hydroxylase activity and about 3% in mephenytoin-hydroxylase activity (poor metabolizers). We tested the hypothesis of a possible over-representation of poor metabolizers among patients with cluster headache. The individual metabolic capacity was determined in 30 cluster headache patients after administration of a test dose of 10 mg of debrisoquine and 100 mg of mephenytoin. Two patients (6.7%) were poor metabolizers of debrisoquine and one (3.3%) a poor metabolizer of mephenytoin. This was no different from the rate of poor metabolizers, 7.1% and 3.3% respectively, in a reference panel of healthy Swedish volunteers. PMID- 1623512 TI - Accompanying symptoms of cluster attacks: their relevance to the diagnostic criteria. AB - Two-hundred-and-fifty-one consecutive cluster headache (CH) patients referred to the Pavia and Parma Headache Centers were evaluated in order to verify the presence and recurrence of one or more autonomic symptoms. Data obtained show that in 2.8% of patients cluster attacks were not accompanied by localized autonomic symptoms, thus confirming the report of Ekbom. We observed a high prevalence of photophobia, nausea and vomiting. The IHS diagnostic criteria for CH may need to be modified. The high frequency of "general" autonomic symptoms seems to suggest a component of "central" drive in the physiopathology of cluster headache. PMID- 1623513 TI - A double-blind study of ibuprofen versus placebo in the treatment of acute migraine attacks. AB - The efficacy of ibuprofen, a non-steroidal anti-inflammatory drug, was assessed in the acute treatment of migraine. Twenty-five patients completed a double-blind placebo-controlled multicrossover trial. The initial dose of ibuprofen was 1200 mg. Six migraine attacks were randomly treated in each patient, three with ibuprofen and three with placebo. The results indicated a statistically significant reduction in the duration of the migraine attacks and also a statistically significant reduction in the severity of headache and nausea in the ibuprofen-treated attacks. The use of additional medication was significantly reduced in the ibuprofen-treated attacks (25.6% vs 57.5%). No serious side effects were reported. Ibuprofen is valuable in the treatment of acute migraine attacks. PMID- 1623514 TI - Cluster headache: alterations in heart rate, blood pressure and orthostatic responses during spontaneous attacks. AB - Changes in heart rate and blood pressure (BP) have been monitored beat-to-beat in a cluster headache patient with and without attacks using a non-invasive Doppler servo method. Two attacks were monitored and during one of them a tilt test was carried out. The variability of heart rate and BP was greater during the attack than during the interparoxysmal period. A marked bradycardia occurred during attacks. Systolic BP increased slightly. There was no heart rate increase after tilting during the attack, whereas this was present invariably during tests carried out interparoxysmally. BP changes during "attack tilt" were difficult to evaluate because of large variation. This may be the first observation of a baroreflex arc dysfunction during a cluster headache attack. PMID- 1623515 TI - Unilateral facial pain as the first symptom of lung cancer: are there diagnostic clues? AB - We describe three patients with unilateral facial pain due to non-metastatic lung cancer and review 11 published cases. Pain, most frequently located on the right side and around the ear, as well as digital clubbing can be clues to an early diagnosis. Compression of the vagus nerve by the tumour or by mediastinal adenopathy is most likely responsible for the facial pain and could play a role in pulmonary osteoarthropathy. PMID- 1623516 TI - Nopp140 shuttles on tracks between nucleolus and cytoplasm. AB - Nopp140 is a nucleolar phosphoprotein of 140 kd that we originally identified and purified as a nuclear localization signal (NLS)-binding protein. Molecular characterization revealed a 10-fold repeated motif of highly conserved acidic serine clusters that contain an abundance of phosphorylation consensus sites for casein kinase II (CK II). Indeed, Nopp140 is one of the most phosphorylated proteins in the cell, and NLS binding was dependent on phosphorylation. Nopp140 was shown to shuttle between the nucleolus and the cytoplasm. Shuttling is likely to proceed on tracks that were revealed by immunoelectron microscopy. These tracks extend from the dense fibrillar component of the nucleolus across the nucleoplasm to some nuclear pore complexes. We suggest that Nopp140 functions as a chaperone for import into and/or export from the nucleolus. PMID- 1623517 TI - Regulation of the cdc25 protein during the cell cycle in Xenopus extracts. AB - The cdc25 protein is a highly specific tyrosine phosphatase that triggers mitosis by dephosphorylating the cdc2 protein kinase. Using Xenopus extracts, we have found that the cdc25 protein is active at a low level throughout interphase. Near the onset of mitosis, the cdc25 protein undergoes a marked elevation in phosphatase activity that coincides with an extensive phosphorylation of the protein in its N-terminal region. In vitro dephosphorylation of this hyperphosphorylated form of cdc25 reduces its phosphatase activity back to the interphase level. Moreover, treatment of interphase Xenopus extracts with okadaic acid, a phosphatase inhibitor that accelerates the entry into mitosis, elicits both the premature hyperphosphorylation of cdc25 and the stimulation of its cdc2 specific tyrosine phosphatase activity. These experiments demonstrate the existence of a cdc25 regulatory system consisting of both a stimulatory kinase that phosphorylates a putative regulatory domain of the cdc25 protein and an inhibitory serine/threonine phosphatase that counteracts this kinase activity. PMID- 1623518 TI - Ras-induced hyperplasia occurs with mutation of p53, but activated ras and myc together can induce carcinoma without p53 mutation. AB - Using a reconstituted mouse prostate organ, the effects on endogenous p53 expression of the ras oncogene or of the ras + myc oncogenes were investigated. In this system the ras gene alone causes mild hyperplasia, but the combination of ras and myc leads to the formation of carcinomas. Surprisingly, while p53 mutations were found in cells derived from the reconstituted organs containing ras alone, no such mutations were found in the ras + myc-transformed cells. Their growth, unlike that of the cells containing ras alone, was not inhibited by transfection with plasmids encoding wild-type human p53. We suggest that expression of both activated ras and myc genes bypasses the need for p53 mutation by neutralizing the tumor suppressor activity of normal p53. PMID- 1623519 TI - A role for RNAase MRP in mitochondrial RNA processing. PMID- 1623520 TI - The pie-1 and mex-1 genes and maternal control of blastomere identity in early C. elegans embryos. AB - During C. elegans embryogenesis an 8-cell stage blastomere, called MS, undergoes a reproducible cleavage pattern, producing pharyngeal cells, body wall muscles, and cell deaths. We show here that maternal-effect mutations in the pie-1 and mex 1 genes cause additional 8-cell stage blastomeres to adopt a fate very similar to that of the wild-type MS blastomere. In pie-1 mutants one additional posterior blastomere adopts an MS-like fate, and in mex-1 mutants four additional anterior blastomeres adopt an MS-like fate. We propose that maternally provided pie-1(+) and mex-1(+) gene products may function in the early embryo to localize or regulate factors that determine the fate of the MS blastomere. PMID- 1623521 TI - Elicitor- and wound-induced oxidative cross-linking of a proline-rich plant cell wall protein: a novel, rapid defense response. AB - Treatment of bean or soybean cells with fungal elicitor or glutathione causes a rapid insolubilization of preexisting (hydroxy)proline-rich structural proteins in the cell wall. This insolubilization, which involves H2O2-mediated oxidative cross-linking, is initiated within 2 min and is complete within 10 min under optimal conditions, and hence, precedes the expression of transcription-dependent defenses. Cross-linking is also under developmental control during hypocotyl growth and in tissues subject to mechanical stress such as the stem-petiole junction. Stimulus-dependent oxidative cross-linking of wall structural proteins is a novel site of cellular regulation with potentially important functions in cell maturation and toughening of cell walls in the initial stages of plant defense. PMID- 1623522 TI - Cell death and control of cell survival in the oligodendrocyte lineage. AB - Dead cells are observed in many developing animal tissues, but the causes of these normal cell deaths are mostly unknown. We show that about 50% of oligodendrocytes normally die in the developing rat optic nerve, apparently as a result of a competition for limiting amounts of survival signals. Both platelet derived growth factor and insulin-like growth factors are survival factors for newly formed oligodendrocytes and their precursors in culture. Increasing platelet-derived growth factor in the developing optic nerve decreases normal oligodendrocyte death by up to 90% and doubles the number of oligodendrocytes in 4 days. These results suggest that a requirement for survival signals is more general than previously thought and that some normal cell deaths in nonneural tissues may also reflect competition for survival factors. PMID- 1623523 TI - Two distinct members of the ADP-ribosylation factor family of GTP-binding proteins regulate cell-free intra-Golgi transport. AB - We have used an intra-Golgi transport assay to identify GTP-binding proteins involved in regulation of protein traffic. Two soluble proteins of 20 kd were purified by their ability to mediate GTP gamma S-dependent inhibition of transport. These GTP-dependent Golgi binding factors, or GGBFs, exhibit a 3-fold difference in activity and are differentiated by their hydrophobicity, isoelectric points, and apparent size. Removal of 80% of GGBFs from cytosol abolishes GTP gamma S sensitivity but does not affect inhibition by aluminum fluoride. We demonstrate that GGBFs are members of the ADP-ribosylation factor (ARF) family. Recombinant ARF1 exhibits GGBF activity and myristoylation is required. The distinct biochemical properties of GGBFs indicate that members of the ARF family may have related but distinct functions in intracellular transport. PMID- 1623524 TI - An actin-binding site containing a conserved motif of charged amino acid residues is essential for the morphogenic effect of villin. AB - The actin-binding protein villin induces microvillus growth and reorganization of the cytoskeleton in cells that do not normally produce this protein. Transfection of mutagenized villin cDNAs into CV-1 cells was used to show that a conserved, COOH-terminally located cluster of charged amino acid residues (KKEK) is crucial for the morphogenic activity of villin in vivo. In vitro experiments with a 22 amino acid synthetic peptide corresponding to this region of villin provide evidence that this motif is part of an F-actin-binding site that induces G-actin to polymerize. Chemical cross-linking of actin to this peptide, the effects of amino acid substitutions in peptides, and the behavior of villin variants further corroborate the participation of the KKEK sequence in actin contacts. PMID- 1623525 TI - A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction. AB - A new SH2-containing sequence, SHC, was isolated by screening cDNA libraries with SH2 representative DNA probes. The SHC cDNA is predicted to encode overlapping proteins of 46.8 and 51.7 kd that contain a single C-terminal SH2 domain, and an adjacent glycine/proline-rich motif with regions of homology with the alpha 1 chain of collagen, but no identifiable catalytic domain. Anti-SHC antibodies recognized three proteins of 46, 52, and 66 kd in a wide range of mammalian cell lines. These SHC proteins complexed with and were phosphorylated by activated epidermal growth factor receptor. The physical association of SHC proteins with activated receptors was recreated in vitro by using a bacterially expressed SHC SH2 domain. NIH 3T3 mouse fibroblasts that constitutively overexpressed SHC acquired a transformed phenotype in culture and formed tumors in nude mice. These results suggest that the SHC gene products couple activated growth factor receptors to a signaling pathway that regulates the proliferation of mammalian cells. PMID- 1623526 TI - Dentistry in paradise. PMID- 1623528 TI - Pro bono treatment as a marketing tool. PMID- 1623527 TI - The non-complying patient. PMID- 1623529 TI - A comprehensive approach to restorative dentistry. PMID- 1623531 TI - Confronting the AIDS issues. PMID- 1623530 TI - Sales transition for the retiring dentist. PMID- 1623532 TI - Tooting the profession's horn by taking dentistry to the airwaves. PMID- 1623533 TI - Legal aspects of the doctor-patient relationship. PMID- 1623534 TI - Patient retention. PMID- 1623535 TI - Hiring the best. PMID- 1623536 TI - Miracle on 87th street. PMID- 1623537 TI - Lasers in dentistry: soft tissue procedures. PMID- 1623538 TI - Lasers in dentistry: an overview. PMID- 1623540 TI - Periodontal regeneration. PMID- 1623541 TI - Seniors serving society and dentistry. PMID- 1623539 TI - Clinical applications of the law. PMID- 1623542 TI - Juliann S. Bluitt, DDS President 1992-93. PMID- 1623543 TI - Successful marketing on a shoestring: internal marketing. PMID- 1623544 TI - Treating periodontal pockets. PMID- 1623545 TI - The glass ceiling. PMID- 1623546 TI - Parents, children and dentistry. PMID- 1623547 TI - Productive staff meetings. PMID- 1623548 TI - A common sense approach to investing for income. PMID- 1623549 TI - Detection of Fc receptors for IgA on rat alveolar and peritoneal macrophages. AB - The presence of Fc receptors for IgA on alveolar macrophages was determined by rosette assay and immunogold labeling. IgA-mediated phagocytosis by alveolar macrophages was observed. Results of these assays were compared between rats receiving no treatment and those receiving long-term cortisone administration. Sheep erythrocytes coated with dextran and an IgA monoclonal antibody specific for the alpha 1,3 linkages of dextran bound to 16% of alveolar macrophages. However, peritoneal macrophages did not form rosettes with dextran-IgA-coated erythrocytes. Immunogold labeling by transmission electron microscopy revealed that most Fc receptors for IgA were found on the membrane of pseudopodia of activated alveolar macrophages. Long-term cortisone administration diminished the phagocytosis and phagocytic index of alveolar macrophages, thereby contributing to decreased host resistance to infection (e.g., Pneumocystis carinii pneumonia). PMID- 1623550 TI - Different time course patterns of local expression of delayed-type hypersensitivity to sheep red blood cells in mice. AB - The delayed-type hypersensitivity (DTH) reaction, a peripheral expression of cell mediated immunity is still a crucial in vivo immunological test. Nevertheless, the biological significance of its time course remains unclear. Thus, an exhaustive study of DTH was undertaken in mice immunized with increasing doses of sheep red blood cells (SRBC) inoculated intravenously (iv) or subcutaneously. The results showed that overall DTH reactions peaked at 18 hr except in mice iv immunized with the lowest doses (10(5) and 10(6)) and elicited at Day 4. The protracted DTH reaction was shown to be associated with an histological picture of tuberculin-type reaction. A part of the 18-hr DTH reaction is mediated by serum in mice inoculated with large doses of SRBC; nevertheless, numeration by limiting dilution analysis of circulating DTH cells showed that the frequency of these cells correlates with the 18-hr DTH level. The protracted DTH shown at 42 and 48 hr, 4 days after immunization with 10(5) and 10(6) SRBC, could not be transferred in naive recipients with immune spleen cells; it was independent of the antigen life span and did not result from immunization modulation at the bone marrow level on recruitable cells. PMID- 1623551 TI - Genetic control of immune responses to the 18-kDa protein of Mycobacterium leprae. Different TH1 subsets may be involved in proliferative and delayed-type hypersensitivity responses. AB - In vitro and in vivo responses to the 18-kDa protein of Mycobacterium leprae have been analysed in different strains of mice. Lymphocytes from BALB/cJ (H-2d), BALB.B (H-2b), B10.BR (H-2k), and B10.M (H-2f) mice primed with 18-kDa protein yielded high T cell proliferative responses, while those from C57BL/10J (H-2b) mice yielded lower responses. Both H-2 and non-H-2 genes contributed to the magnitude of responsiveness. F1 mice from high and low responder strains showed high responsiveness to the 18-kDa protein. Supernatants from lymph node cell cultures prepared from 18-kDa protein-immunised BALB/cJ, B10.BR, and C57BL/10J mice contained IL-2 but no IL-4, indicating that activated T cells from both high and low responder mice were of a TH1 phenotype. Cell cultures from low responder C57BL/10J mice produced less IL-2 than those from high responders. The low responsiveness to the 18-kDa protein in proliferative assays might be due to a low frequency of antigen-specific T cells in the C57BL/10J mouse strain. BALB/cJ, C57BL/10J, and F1 (BALB/cJ x B10.BR) mouse strains were tested for in vivo DTH reactions to the 18-kDa protein. All strains, including C57BL/10J, were high DTH responders. Although DTH effector cells and 18-kDa protein-specific proliferative T cells belong to the TH1 subset, our data comparing high and low responder status indicate that distinct TH1 subpopulations are stimulated in response to the 18-kDa protein of M. leprae. PMID- 1623552 TI - The proportion of symmetric and asymmetric IgG antibody molecules synthesized by a cellular clone (hybridoma) can be regulated by placental culture supernatants. AB - The purpose of the present work was to establish whether the placenta is producing factors favoring an increased synthesis of asymmetric IgG antibodies which are known to assume a protective effect upon paternal antigens to which they largely are specific. In this way they can contribute to fetal survival in the maternal uterine environment. The hybridoma cell lines OKT8 (anti-CD8) and 112B4 (anti-DNP) were used in this respect since they synthesized both symmetric and asymmetric molecules of the IgG2a and IgG1 subclasses, respectively, murine isotypes in which anti-paternal antibodies have been detected. The cells were cultured in RPMI 1640 medium supplemented with 10% BCS and different amounts (5, 10, and 20%) of human placental supernatant. After incubation for 3 days at 37 degrees C in a humid chamber containing 5% CO2 the cells were centrifuged and the antibodies were obtained from the culture medium by a purification procedure involving precipitation at 50% ammonium sulfate saturation followed by DEAE cellulose chromatography. Symmetric and asymmetric antibodies were separated by Con A-Sepharose affinity chromatography, the latter lectin retaining selectively only asymmetric IgG molecules. Both OKT8 and 112B4 hybridomas presenting a stable background synthesis of 15-17% of asymmetric antibodies have shown an increased level reaching 27-28% of these molecules in the presence of 5-10% placental supernatant added to the RPMI 1640 culture medium. These results clearly show that placental factors can up-regulate efficiently the synthesis of asymmetric IgG molecules of different isotypes secreted by plasma cells. PMID- 1623553 TI - Assembly of MHC class I molecules in ex vivo carcinoma cells induced by IFN-gamma or by a binding peptide. AB - It has been reported that the assembly of MHC class I molecules in mutagenized cell lines could be induced by specific binding peptides. We have now demonstrated that the defect in assembly between heavy and light chains of class I molecules naturally occurred in tumor cells of one spontaneous ovarian carcinoma detected by one-dimensional isoelectric focusing of immunoprecipitates with anti-monomorphic class I MAb (W6/32) and by immunostaining with free heavy chain and beta 2m-specific MAbs. In vitro treatment of the tumor cells with IFN gamma induced the assembly and surface expression of majority class I molecules (A2.1, B7, B15, Cw6, Cw7 out of A2.1, A2*, B7, B15, Cw6, Cw7). Moreover, assembly of A2 and Cw6 was induced by exposure of the tumor cells to a HLA A2-binding peptide K62 derived from influenza A matrix protein. Autologous blood T lymphocytes were activated in mixed lymphocyte-tumor cell culture (MLTC) by the IFN-gamma-treated but not by the unmanipulated tumor cells. Although activated lymphocytes damaged both IFN-gamma-treated and untreated tumor cells, the alpha class I MAb (W6/32) efficiently inhibited the lysis of IFN-gamma-treated targets, but not the untreated targets. These results indicate that the defect of MHC class I assembly may result in the escape of tumor cells from immune response. PMID- 1623554 TI - Transient down-regulation of PKC-zeta RNA following crosslinking of membrane IgM on WEHI-231 B lymphoma cells. AB - Regulation of protein kinase C (PKC) isoform mRNAs has been studied in the immature, murine B lymphoma WEHI-231 by the MAPPing protocol and by slot blot analysis of unamplified mRNA. This membrane IgM (mIgM)-positive cell line has been previously used as a model to study signal transduction by mIgM in immature B lymphocytes and the role of those signals in the induction of immune tolerance in the B cell compartment. Stimulation of the cells by anti-mu antibodies, phorbol ester, or Ca2+ ionophore caused growth arrest and death of the cells. IL 4 and IL 5 slowed the growth of the cells. Of these stimuli, only anti-mu stimulation affected PKC mRNA levels. Anti-mu treatment caused a transient decrease in the amount of PKC-zeta isoform mRNA within 3 hr. Within 24 hr levels returned toward normal. Anti-mu had little or no effect on the expression of mRNA for the alpha, beta, delta, or epsilon isoforms of PKC. WEHI-231 cells do not express PKC-gamma. Although anti-mu treatment blocked progression of the cells from the G0/G1 stage into the S phase of cell cycle, viable sort selected cells in either the G0/G1 or the S/G2/M phases showed no clear difference in the expression of PKC-zeta message. Thus, there is not preferential regulation of expression of PKC-zeta during stages of the cell cycle. The results show that mIgM on WEHI-231 cells can transduce a signal that is not mediated by PKC or Ca2+ mobilization alone. The signal causes transient, selective down-regulation of mRNA encoding the zeta PKC isoform. PMID- 1623555 TI - Persistence of lpr/lpr-derived IgG2a secreting B cells in normal----lpr/lpr adult radiation chimeras or lpr/lpr----normal kidney capsule chimeras. AB - Lethally irradiated MRL/lpr mice reconstituted with bone marrow stem cells from a normal mouse strain develop a state of split hematopoietic chimerism; erythrocytes, granulocytes, and macrophages are derived from the normal stem cell inoculum while the peripheral T lymphocytes are derived from radioresistant lpr host cells. Moreover, these mice have normal levels of serum IgM and IgG2a produced by radioresistant host B cells, even though they have relatively few sIgM+ B cells. In order to better understand the differentiation and regulation of B cells present in these chimeric mice, the current study was undertaken to localize and to assess the functional capacity of the lpr B cells producing the serum antibodies. Surface IgG2a+ cells could not be found in the spleen or lymph nodes of these mice, but large lymphocytes containing cytoplasmic IgG2 of host (lpr) allotype could be readily detected, even though they constituted less than 1% of the total spleen population. The host-derived serum IgG2 and IgG2+ cells were even present in the spleens of "leaky" mice that had relatively normal numbers of donor-derived sIgM+ B cells. These lpr B cells secreted IgG2a antibody that bound ssDNA, but they could not respond to immunization with SRBC. These results indicate that the lpr-derived radioresistant B cells have a limited capacity for proliferation and are already committed to the memory lineage. The presence of similar B cells in normal mice transplanted with neonatal lpr/lpr spleen fragments suggests that lpr/lpr B cell development is inherently abnormal. PMID- 1623556 TI - Production of macrophage colony-stimulating factor (M-CSF) by human monocytes is differentially regulated by GM-CSF, TNF alpha, and IFN-gamma. AB - Macrophage colony-stimulating factor (M-CSF) stimulates the survival, proliferation, and differentiation of mononuclear phagocytes. In this study, the qualitative and relative quantitative ability of various cytokines to induce and to synergize in M-CSF production by monocytes was studied. GM-CSF and the phorbolester PMA were strong inducers of M-CSF m-RNA expression. This was correlated closely with the secretion of M-CSF protein as measured in the murine M-NFS-60 cell line bioassay. Both TNF alpha and IFN-gamma enhanced M-CSF message levels induced by GM-CSF, but only TNF alpha synergized with GM-CSF in the induction of M-CSF protein secretion. M-CSF transcripts induced by TNF alpha and IFN-gamma were much lower compared to those induced by GM-CSF and PMA and were not accompanied by the secretion of M-CSF protein. In addition, costimulation of cells with TNF alpha and IFN-gamma did not result in M-CSF production. Although M CSF did not induce its own message, it further enhanced M-CSF transcripts induced by GM-CSF. LPS also failed to induce M-CSF message or secretion. These results show that cytokines differ in their ability to induce or to synergize in the induction of biologically active M-CSF protein. They further demonstrate that M CSF message expression, induced by cytokines, does not always correlate with M CSF protein secretion. PMID- 1623557 TI - The unique killing of embryo-derived teratocarcinoma cells by nonactivated murine macrophages is not due to a lack of H-2 antigen expression. AB - It is well documented that activated macrophages, but not nonactivated ones, kill tumor cells in vitro without damaging normal cells. We, however, have previously shown that embryo-derived teratocarcinoma cells (F9, P19, PCC4) are efficiently killed by nonactivated macrophages as well as by activated ones. Whereas other tumor cells are killed extracellularly by macrophages, we found that F9 teratocarcinoma cells are phagocytosed alive by macrophages and subsequently killed intracellularly by a process dependent on intact lysosomal function. Neither the H-2 antigens nor the mRNAs for the alpha-chain and beta 2 microglobulin are detectable in embryo-derived teratocarcinoma cells. An obvious explanation for this unique killing is that the nonactivated macrophages recognize and kill these cells due to their lack of class I MHC antigen expression, assuming that class I MHC gene products on the target cells switch off the cytolytic machinery of nonactivated macrophages. Our present findings demonstrate that there is no correlation between H-2 antigen expression on tumor cells and their susceptibility to killing by macrophages. Retinoic acid differentiated F9 cells and P19 cells expressing H-2 antigen after exposure to MAF (IFN-gamma) were sensitive to the killing by nonactivated macrophages. Hybrids that arose from fusion of P19 teratocarcinoma cells with embryonal normal fibroblasts (C57BL/6), which displayed the morphology of embryonal carcinoma stem cells and expressed H-2 antigens, were also sensitive to the killing by nonactivated macrophages. On the other hand, the H-2-negative testicular 402AX teratocarcinoma cells and K1735P melanoma cells were both resistant to the killing by nonactivated macrophages. We concluded that the unique killing of embryo-derived teratocarcinoma cells by nonactivated murine macrophages is not related to a lack of H-2 antigen expression. PMID- 1623558 TI - Effect of priming with a thymus-independent antigen on susceptibility to B-cell tolerance. AB - The effects of priming on the susceptibility of B-cell subsets to tolerance induction have been tested in a model system in which anti-immunoglobulin (anti Ig) has been employed as a surrogate for tolerogen. T-cell-depleted B cells were primed in vitro with fluorescein or trinitrophenylated Ficoll (a thymus independent (TI) antigen) and then exposed overnight to anti-Ig to attempt to induce B-cell anergy. Primed cells were relatively resistant to this tolerance protocol and resistance was hapten specific. The dose response and kinetics suggested that this process was not due to receptor blockade or modulation, but was an active process. Moreover, this priming for resistance to tolerance was reproduced in vivo upon intraperitoneal treatment with haptenated Ficoll. Such in vivo priming for tolerance resistance was long-lasting and did not occur with a thymus-dependent priming protocol with fluoresceinated hemocyanin. These results are discussed in terms of TI priming to drive B cells into cycle and express novel functional and phenotypic properties. PMID- 1623559 TI - A nonspecific inhibitor of contact sensitivity elaborated by macrophages: genetic restriction in its production but not in its action. AB - It is known that macrophages armed with hapten-specific T suppressor factor (TsF) and then exposed to antigen (haptenized spleen cells) liberate a nonspecific inhibitor of the transfer of contact sensitivity (CS). This is called macrophage suppressor factor (MSF). This paper shows that MSF is only released when the source of the TsF and the haptenized spleen cells share the same I-J subregion. This is based on the comparison of B10.A(3R) and B10.A(5R) mice. In contrast, the action of MSF is antigen nonspecific and genetically unrestricted. In these respects it resembles the antigen-nonspecific inhibitor (nsTsF-1) made by the T acceptor cell when armed with TsF. However, it differs from nsTsF-1 in acting directly on the I-A- population which transfers contact sensitivity and not indirectly via I-A+ T cells. In vitro, MSF fails to inhibit the proliferative response of lymph node cells to specific antigen and their production of IL-3 activity, IFN-tau, and IL-2. This indicates that MSF is not a global inhibitor of T cell activity. The finding that MSF inhibits systemic passive transfer of contact sensitivity, but has no effect on local passive transfer strongly supports the view that MSF affects the arrival of certain cells critical for the development of the reaction to the skin challenge site. PMID- 1623560 TI - Interferon-gamma stimulates lipid metabolism in human monocytes. AB - In nonactivated human monocytes, radiolabeled oleic, arachidonic, and palmitic acids are primarily incorporated into neutral lipids and phosphatidylcholine. Each of these fatty acids is also incorporated into phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and sphingomyelin in characteristic proportions which do not differ between donors. The phospholipid head group precursors, choline and serine, are incorporated into phosphatidylcholine, and phosphatidylserine and serine is incorporated into phosphatidylethanolamine and sphingomyelin. The incorporation of these lipid precursors and the total lipid content of monocytes activated with interferon-gamma were compared to those of nonactivated monocytes. Fatty acid incorporation into interferon-gamma-activated monocytes was dramatically increased, particularly for palmitic acid. Palmitic acid incorporation into phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and sphingomyelin was increased in activated cells by 167-387% at 2 hr and 215-274% at 4 hr compared to that of controls. The greatest increase in incorporation was for palmitic acid into sphingomyelin. Incorporation of arachidonic acid into phosphatidylinositol and serine into phosphatidylethanolamine was also increased in the interferon-gamma activated monocytes. The total lipid content of activated and nonactivated monocytes did not differ. These results suggest that IFN-gamma activation induces a short-term stimulation of phospholipid metabolism which does not alter the gross lipid composition. Such modifications of phospholipid metabolism may be important in signal transduction as well as an indication of functional changes in the membranes of activated macrophages. PMID- 1623561 TI - Interleukin 6 modulates c-sis gene expression in cultured human endothelial cells. AB - Human vascular endothelial cells secrete platelet-derived growth factor (PDGF) like polypeptides which may mediate some of the vascular effects in the inflammatory process. We have demonstrated that IL-6 caused a significant increase in the mRNA level of the c-sis gene (PDGF B chain) in cultured human endothelial cells. IL-1 alpha and IL-1 beta also increased c-sis mRNA transcripts after an extended incubation period and both cytokines acted synergistically with IL-6 in increasing c-sis expression. Tumor necrosis factor enhanced the accumulation of c-sis mRNA and interferon-gamma decreased its level. In the inflammatory process specific cytokines can modulate c-sis expression in human endothelial cells. Their subsequent production of PDGF-like polypeptides could stimulate cell migration and proliferation, and cause the release of vascular inflammatory mediators. PMID- 1623562 TI - In vivo synergistic effect of the immunomodulator AS101 and the PKC inducer bryostatin. AB - The immunomodulator AS101 has recently been found to have radioprotective properties when injected prior to sublethal and lethal doses of irradiation. In addition, this compound was found to protect mice from hemopoietic damage caused by sublethal doses of cyclophosphamide (CYP) and to increase the rate of survival of mice treated with lethal doses of CYP. AS101 was previously shown to exert a synergistic effect with the PKC-inducer bryostatin in cytokine secretion in vitro. The present studies were designed to evaluate the effects of in vivo combined treatment with AS101 and bryostatin on bone marrow and spleen cellularity and on the number of committed progenitors in the bone marrow at various points of time after their treatment with a sublethal dose of CYP or irradiation. In addition, the combined effect was tested on the survival of mice irradiated with a lethal dose of irradiation. Our data show the presence of synergism which greatly enhances the number of bone marrow and spleen cells 48 hr and 9 days after CYP treatment or irradiation. The combined effect was also demonstrated when bone marrow colony-forming units granulocyte-macrophage (CFU GM) progenitor cells were evaluated. Moreover, AS101 and bryostatin synergized in their protective effects against lethal damages of irradiation. These results strongly suggest that bryostatin, which lacks tumor-promoting activity, is a particularly good candidate in combination with AS101 for treatment in vivo in counteracting chemotherapy- or radiation-induced hematopoietic suppression or in generally improving the restoration of immune response under conditions involving immune or hemopoietic damage. PMID- 1623563 TI - Identification of functional T cell subsets and surface antigen changes during activation as they relate to RT6. AB - The functional and phenotypic heterogeneity of the rat peripheral T lymphocyte antigen RT6 has been examined. The in vivo popliteal graft-vs-host reaction (GvHR), in vitro MLR, and the generation and effector populations of cytotoxic T lymphocyte were used to examine the response of RT6-positive (RT6+) or -negative (RT6-) subsets of CD4 and CD8 T cells to alloantigen. T lymphocytes with the CD4+RT6+ surface phenotype are necessary and sufficient for inducing a strong GvHR. T lymphocytes with the CD4+RT6-, CD8+RT6+, and CD8+RT6- surface phenotypes do not contribute or induce a strong GvHR. Both the CD4+RT6+ and the CD4+RT6- T cells proliferate in the MLR assay. CTL precursors are a mixture of CD8+RT6+ and CD8+RT6- phenotypes, but only cells bearing the RT6- phenotype are potent CTL effector cells. Data presented in this paper also demonstrate that the RT6.1 alloantigen, present on the majority of rat T cells, modulates on cortisone resistant thymocytes (CRT) and peripheral T cells. Although freshly isolated CRTs do not express the RT6.1 epitope, RT6+ cells develop when CRTs are placed into culture. Peripheral T cells that are RT6- will also become RT6+ in culture. Stimulation of T cell cultures with a mitogen causes the loss of the RT6.1 antigen, as detected by the DS4.23 mAb. The effect is more pronounced in cultures of CRTs than peripheral T cells. Following a return to a nonactivated state, the T cells reexpress RT6. The loss and reexpression of RT6 may be related to activation and/or differentiation of T cells. PMID- 1623564 TI - Stimulation of interleukin-6 production by corticotropin-releasing factor. AB - Based on the immune-modulating properties of corticotropin-releasing factor (CRF), the effect of this peptide for interleukin-6 (IL-6) production was investigated. Using human peripheral blood mononuclear cells (MNC), the amount of bioactive IL-6 produced was significantly (P less than or equal to 0.05) increased by CRF (10(-10) to 10(-7) M range). However, the IL-6 production of lipopolysaccharide-treated MNC cultures was not modified. At concentrations of greater than or equal to 10 nM, CRF and two analogous peptides (Tyr-CRF and alpha helical CRF) elicited 16- to 21-fold stimulation of IL-6 production by MNC. Purified monocytes, but not purified lymphocytes, were the cells that responded to CRF action exhibiting nearly 19-fold stimulation at 100 nM concentration. The CRF-induced production of IL-6 cytokine by peripheral blood MNC may suggest a messenger role for this neurohormone in the feedback control of neuroendocrine immune circuitry. PMID- 1623565 TI - Role of uncultured human melanoma cells in the proliferation of autologous tumor specific cytotoxic T lymphocytes. AB - The role of uncultured melanoma cells in the proliferation of autologous tumor specific cytotoxic T lymphocytes (CTLs) was investigated. Uncultured autologous tumor cells by themselves induced modest, but significant, proliferation in 10 of 13 (77%) CTL clones and in only two of nine non-CTL clones. Uncultured allogenic melanoma cells mostly failed to induce CTL proliferation. Autologous tumor induced CTL proliferation declined with increasing age of the culture. It did not correlate with IL-2 receptor-alpha expression or was not inhibited by addition of anti-IL-2 antibody to the culture. It was inhibited by pretreatment of tumor cells with anti-MHC class II, but not -MHC class I mAb. IL-2 alone was sufficient for the potent proliferation of five of nine CTL clones. In all these five CTL clones, autologous tumor cells suppressed IL-2-induced proliferation. The remaining four CTL clones, however, required both uncultured autologous melanoma cells and IL-2 for the proliferation. IL-4 or IL-6, in particular IL-6, facilitated IL-2-induced CTL proliferation, but not their cytotoxicity. In summary, uncultured melanoma cells by themselves induced modest levels of CTL proliferation in the context of MHC class II antigens, whereas they suppressed IL 2-induced CTL proliferation in more than half of the clones. PMID- 1623566 TI - Adoptive transfer of the entire gld (generalized lymphoproliferative disease) syndrome in nude beige mice by a single gld thymocyte graft. AB - C57BL/6 nude beige mice (B6 nubq; no T cell, no NK activity) were used as recipients for the adoptive transfer of thymocytes from B6 gld mice (generalized lymphoproliferative disease) which are a model of systemic lupus erythematous. The [gld----nubg] chimeras showed several similarities with gld control mice including the T cell disorders (lymphoproliferation and Con A-response deficiency of splenocytes) and B cell disorders (hyperglobulinemia and elevated anti-single stranded DNA antibody titers). This suggests that the gld lymphoproliferative disorder has a thymic origin (and does not result from an abnormally extrathymic T cell development) and that the gld T cells have an essential role for the emergence of the disorders of both the T and B cells. PMID- 1623567 TI - Failure of signaling through a chimeric class I-immunoglobulin molecule expressed on the surface of transfected B lymphoma cells and cells of transgenic mice. AB - To test the possibility that the crosslinkage of molecules expressing a transmembrane region derived from the membrane form of the mu immunoglobulin heavy chain would be sufficient for signal transduction in B cells, a chimeric gene (Kk-mu) consisting of extracellular exons of the class I gene H-2Kk and the transmembrane and cytosolic exons of the mu constant region gene was introduced into WEHI-231 B lymphoma cells and into mouse blastocysts. A protein consistent with the predicted product of the Kk-mu gene was expressed in a transfected cell clone (S18) and in transgenic mice. Crosslinkage of Kk-mu protein with soluble, Sepharose-bound, or dextran-conjugated anti-H-2Kk antibodies failed to induce the accumulation of inositol phosphates or to elevate intracellular calcium concentrations in either S18 cells or B lymphocytes from transgenic mice. Furthermore, crosslinkage of Kk-mu did not inhibit growth of S18 cells or stimulate DNA synthesis by transgenic B cells, in the presence or absence of interleukin-4. The failure of crosslinkage of Kk-mu to initiate detectable intracellular biochemical change or to effect cellular growth suggests that simple crosslinkage of molecules expressing the mu transmembrane region is not sufficient to transduce signals in B cells. PMID- 1623568 TI - Joseph Discipio is Alumnus of the Year. PMID- 1623569 TI - Respiratory system mechanics in patients treated with isotonic or hypertonic NaCl solutions. AB - Twenty-one patients who underwent elective surgery for coronary artery bypass were studied right after chest wall closure. They were anesthetized, paralyzed, and artificially ventilated with a constant-flow ventilator. Airflow, changes in lung volume, and tracheal pressure were measured. Respiratory system resistance (Rrs,max) was partitioned into its homogeneous (Rrs,min) and uneven (Rrs,u) components. Respiratory system elastance (Ers) was also measured. The subjects were randomly divided into two groups injected with test solutions just after chest wall closure: eleven patients received isotonic saline (0.9% NaCl solution), whereas the remaining ten were injected with hypertonic saline (7.5% NaCl solution). In all patients, mechanical parameters were measured at six different times: just before infusion, at 5 and 10 min (end of infusion); and at 15, 20, and 25 min after beginning of injection. No statistically significant differences were observed in respiratory system mechanical parameters between groups or between different times within each group. Our data suggest that hypertonic saline infusion does not result in significant changes in respiratory system mechanics in patients submitted to coronary artery bypass. PMID- 1623570 TI - Relationship between changes in serum estrone levels and outcome in human males with septic shock. AB - The effect of septic shock on the production of estrogens, other steroid hormones, and gonadotropins in men was investigated. Two groups of male patients in the early septic shock were studied over 3 days following their admission to the Intensive Care Unit. Group I (n = 9) patients recovered and group II (n = 6) patients died. The simplified acute physiological score was 13.5 +/- 1.5 for group I and 21.2 +/- 2.3 for group II (P less than .05). In group I patients, estrogen levels (particularly E1) were high on day 1 and decreased progressively (day 1: 3,515 +/- 884 pmol/L, day 2: 2,450 +/- 292 pmol/L, and day 3: 1,043 +/- 255 pmol/L). In group II patients, estrone levels were as high as in group I on day 1, but increased throughout the 3 days (day 1: 3,250 +/- 1,200 pmol/L, day 2: 4,495 +/- 930 pmol/L, and day 3: 6,123 +/- 966 pmol/L). There were few changes in gonadotropins and other steroid hormones, except that the testosterone levels were below normal in both patient groups, while cortisol was elevated in group II. The changes in serum E1 may provide an accurate marker of individual outcome. PMID- 1623571 TI - ATP-MgCl2 restores the depressed cardiac output following trauma and severe hemorrhage even in the absence of blood resuscitation. AB - A number of beneficial effects of ATP-MgCl2 administration have been demonstrated in preheparinized models of shock and ischemia. However, it is not known whether ATP-MgCl2 restores and maintains the depressed cardiac output in a nonheparinized model of trauma and severe hemorrhage in which resuscitation following shock was provided only with crystalloid. To study this, rats underwent a midline laparotomy (i.e., trauma induced) and were then bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximum shed blood volume was returned in the form of Ringer's lactate (RL). Animals were then resuscitated with 4 times the volume of shed blood with RL (4 X RL) during and following which ATP-MgCl2 (50 mumol/kg body weight each or an equivalent volume of normal saline) was infused intravenously. Cardiac output was determined every 15-30 min for 4.5 hr, using an in vivo hemoreflectometer and indocyanine green dilution technique. Resuscitation with 4 X RL transiently restored but did not maintain cardiac output; however, ATP-MgCl2 treatment restored and maintained cardiac output at control values. ATP-MgCl2 infusion also significantly decreased total peripheral resistance and attenuated tissue water content. Thus, ATP-MgCl2 appears to be a promising adjunct to the treatment of trauma-hemorrhage even in the absence of blood resuscitation. PMID- 1623572 TI - Differentiation of the anti-shock effect of ulinastatin from steroid hormone, by the continuous observation of microcirculation dynamics. AB - The effects of ulinastatin (UST) and methyl prednisolone (MPS) on endotoxin induced shock were compared by the criterion of microcirculation dynamics in rat mesenterium and plasma phospholipase A2 (PLA2) activity in modified Shwartzman reaction model. The mean arterial pressure and red cell velocity were well maintained when MPS was administered during endotoxin induced shock. In the case of UST, superior anti-shock effects, indicated by reduced vasoconstriction, were obtained when it was administered prior to endotoxin induced shock. The anti shock effect of UST, similar to MPS, was supported by the change of serum PLA2 activity. Therefore, concerning the administration timing of anti-shock drugs, MPS should be administered after shock occurs, and UST is most effective as a prophylactic treatment. UST has an anti-shock effect like steroid hormone. PMID- 1623573 TI - Effects of hepatic inflow occlusion on changes in plasma potassium, histamine, and norepinephrine in rats. AB - To evaluate the effects of hepatic inflow occlusion without the shunt, the physiological differences were compared in three groups of rats in which the hepatoduodenal ligament was occluded for 15 min, 30 min, and 60 min. The survival rate significantly decreased in the 60 min occlusion group (53.6%) when compared with that of the 15 min and 30 min occlusion groups (95% and 91.6%, respectively). The significant differences in the changes in blood pressure (BP), the values of plasma potassium, histamine (HIS), norepinephrine (NE), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the values of hematocrit (HT) were also observed between the 30 min and 60 min occlusion groups. The results indicate that, in rats, there is a high probability of an irreversible state to shock after 30 min hepatic inflow occlusion when veno venous bypass is not applied. The values of plasma HIS and NE and the values of HT in portal blood were significantly greater than those in the general circulation. The results suggest that splanchnic congestion may have a greater influence than hepatic ischemia has in contributing to the deterioration of the physiological state. PMID- 1623574 TI - A nonlethal intravenous dose of endotoxin influences opsonized zymosan-stimulated [32P]phospholipid turnover in rat alveolar macrophages. AB - The opsonized zymosan-stimulated turnover of 32P-labeled phospholipids was examined in alveolar macrophages from rats 3 hr after intravenous administration of saline or a nonlethal dose of endotoxin. Stimulation resulted in increased incorporation of [32P]PO4 into phosphatidic acid and phosphatidylinositol. Also a decreased [32P]phosphatidylcholine and an increased [32P]lysophosphatidylcholine labeling were observed, suggesting an increased activity of phosphatidylcholine specific phospholipase A2. Endotoxin attenuated these changes in 32P-labeled phospholipids, demonstrating the ability of a nonlethal dose of endotoxin to perturb phospholipid-dependent signal transduction mechanisms in cells isolated from a compartment other than the one in which endotoxin was administered. PMID- 1623575 TI - Pharmacotherapy in shock syndromes: the neglected field of pharmacokinetics and pharmacodynamics. AB - Promising effects of adjuvant drugs in experimental shock models often are not confirmed in subsequent clinical trials, e.g., steroids, fibronectin, naloxone, immunotherapeutics. A key difficulty in establishing a therapeutic benefit in clinical studies, apart from study design shortcomings, is the lack of knowledge and application of principles of clinical pharmacokinetics and -dynamics. In shock states the relationship between an administered fixed dose regimen and the drug effect is strongly influenced by dynamic changes in absorption, distribution, metabolism, and elimination of the drug, all of which vary between individual patients. This article describes several neglected aspects of clinical pharmacology relevant to shock research under clinical conditions and discusses the indications, prerequisites, and limitations of "applied pharmacokinetics." The inclusion of therapeutic drug monitoring in clinical shock studies should be applied more frequently to establish experimental results in the "real world" of ICU settings. PMID- 1623577 TI - The Shock Society. Directory. PMID- 1623576 TI - Shock Society, 15th Annual Conference on Shock. Alabama, June 7-10, 1992. Abstracts. PMID- 1623578 TI - Semi-automated assay of erythrocyte Cu-Zn superoxide dismutase activity. AB - A semi-automated enzymatic colorimetric method for determining Cu-Zn superoxide dismutase (SOD) in erythrocytes using an FP9 parallel analyzer is described. The method is based on the reaction described by McCord and Fridovich (xanthine/xanthine oxidase, ferricytochrome C), which permits kinetic measurements to be determined colorimetrically for the assay of enzyme activity. The coefficients of variation for within- and between-run analyses were less than 6%. The limit of linearity is 3.5-times the mean value of the normal range while recovery of added SOD ranged from 91 to 120%. The method, which is both reliable and simple, allows rapid, simultaneous measurements of multiple samples. PMID- 1623579 TI - Role of serum fasting gastrin in screening for hypergastrinemic syndromes in duodenal ulcer disease. AB - Basal serum gastrin levels were measured in 237 patients with endoscopically confirmed duodenal ulcer and were higher than normal in 16 cases. Protein meal gastrin stimulation was performed on this group of 16 patients and on a control group of 48 patients with normal basal gastrin concentrations but high rates of either ulcer recurrence or of complications (e.g., bleeding or perforation); 21 patients from the two groups were also tested for serum gastrin inhibition with secretin. Four cases (25%) of antral G-cell hyperfunction were found in the first group, plus 1 case compatible with Zollinger-Ellison syndrome (6.2%). Only 1 case (2%) of antral G-cell hyperfunction was found among the 48 controls. These results suggest the clinical utility of routine basal gastrin measurement in screening for hypergastrinemic patients with duodenal ulcer disease. PMID- 1623580 TI - The biochemistry of mammalian senescence. AB - Senescence is a process which, until quite recently, has been the subject of little scientific investigation. Even the word "senescence" is difficult to define, and complex methodological pitfalls have impeded progress. In the past few years, there have been exciting advances in understanding the physiological, cell biological, biochemical, and molecular biological nature of senescence. Changes in membrane function, protein synthesis, DNA structure (including glycosylation, altered tertiary structure, free-radical effects, and loss of telomeric DNA), and changes in gene regulation with age are reviewed. Recent work on changes in responses to transcriptional regulatory proteins and cellular senescence factors, some of which have been identified, is particularly promising and leads to the conclusion that senescence, at least in part, is a programmed process. Despite these advances, the fundamental cause of senescence remains elusive but might, as in the case of other biological processes which are phylogenetically widespread, turn out to be quite simple, and perhaps, even modifiable. PMID- 1623581 TI - Antibody multispecificity in immunoassay interference. AB - Recent findings indicate that many endogenous antibodies exhibit multispecificity. These antibodies exhibit a potential for interference with immunoassays. Antibodies that interfere with immunoassays have been called heterophile or heterophilic antibodies. The purpose of this review is: (1) to identify the nature of heterophile antibodies; (2) to delineate the processes that produce them; (3) to examine the mechanisms by which these antibodies cause interference; and (4) to explore how this information can be used to reduce immunoassay interference. In addition to producing specific antibodies, the process of antibody production gives rise to rudimentary antibodies that are polyspecific; e.g., the antigen-combining site has an affinity for antigens of different chemical composition. This process also generates idiotypic antibodies containing cross-reactive idiotopes. These antibodies along with rheumatoid factors, which are themselves polyspecific and rich in cross-reactive idiotopes, are inherent parts of the process of antibody production, and exhibit multispecificity. Mechanisms by which these antibodies cause immunoassay interference are outlined. These properties of antibodies may have substantial consequence in directing future assays toward greater clinical predictive value. PMID- 1623582 TI - Clinical usefulness of high-pressure liquid chromatographic determination of serum pentamidine in AIDS patients. AB - We have developed a reproducible HPLC method to determine serum pentamidine, which demonstrates good chromatographic performance, and is sensitive enough to measure therapeutic doses. Pentamidine is first extracted from serum by passage through a C-18 extraction cartridge. Potential interfering substances are then removed by washing with 100% methanol. Pentamidine is eluted from the extraction cartridge with 1-heptanesulfonic acid. The extract is chromatographed on a highly deactivated column for basic compounds in the presence of minimal concentrations of 1-heptanesulfonic acid as the pairing agent. Detection is by fluorescence. The method can determine serum pentamidine levels in the range of 15-600 ng/mL free of interference from other drugs. In monitoring pentamidine levels in AIDS patients with Pneumocystis carinii, we found that trough serum levels over 100 ng/mL were associated with toxicity (hypoglycemia or azotemia) in 100% of patients. With levels under 100 ng/mL, signs of toxicity were observed in only 29% of the patients. We conclude that dose adjustment based on serum levels reduces the incidence of toxicity and enhances pentamidine therapy. PMID- 1623583 TI - 1992 Clinical Chemistry Forum: Government regulation: can it guarantee quality in the clinical laboratory? Bethesda, Maryland, November 18-19, 1991. PMID- 1623584 TI - The history of proficiency testing/quality control. AB - The history and origins of proficiency testing of clinical laboratories are reviewed. Since the introduction of proficiency testing in the late 1940s, dramatic improvement in laboratory performance has been demonstrated. Nonetheless, the poor performance found two decades earlier was summoned to support the passage of the Clinical Laboratory Improvement Act of 1967 (CLIA '67). PMID- 1623585 TI - How good are clinical laboratories? An assessment of current performance. AB - The Clinical Laboratory Improvement Act of 1967 and Amendments of 1988 (CLIA '67 and CLIA '88) were enacted to ensure that clinical laboratories within the U.S. provide a quality of service that meets clinical needs for good patient care. Approved proficiency-testing programs are to judge the quality of laboratory testing by promulgated performance criteria. We examine the quality of analytical results reported in 1991 to the New York State Department of Health Proficiency Testing program in light of these criteria and analytical goals, based on medical usefulness. Analytical performance is examined for cholesterol, potassium, sodium, calcium, glucose, aspartate aminotransferase, digoxin, and theophylline. In general, proposed CLIA '88 performance standards are compatible with the current state of practice for the population of laboratories examined. Exceptions appear to be digoxin and sodium (failure rate exceeding average) and most therapeutic substances (low failure rate). Sources of analytical bias relative to an accuracy-based target value must be characterized as method-, laboratory-, or matrix-dependent if regulatory programs are to achieve the objective of improving analytical accuracy across all testing sites. PMID- 1623586 TI - Charts of operational process specifications ("OPSpecs charts") for assessing the precision, accuracy, and quality control needed to satisfy proficiency testing performance criteria. AB - "Operational process specifications" have been derived from an analytical quality planning model to assess the precision, accuracy, and quality control (QC) needed to satisfy Proficiency Testing (PT) criteria. These routine operating specifications are presented in the form of an "OPSpecs chart," which describes the operational limits for imprecision and inaccuracy when a desired level of quality assurance is provided by a specific QC procedure. OPSpecs charts can be used to compare the operational limits for different QC procedures and to select a QC procedure that is appropriate for the precision and accuracy of a specific measurement procedure. To select a QC procedure, one plots the inaccuracy and imprecision observed for a measurement procedure on the OPSpecs chart to define the current operating point, which is then compared with the operational limits of candidate QC procedures. Any QC procedure whose operational limits are greater than the measurement procedure's operating point will provide a known assurance, with the percent chance specified by the OPSpecs chart, that critical analytical errors will be detected. OPSpecs charts for a 10% PT criterion are presented to illustrate the selection of QC procedures for measurement procedures with different amounts of imprecision and inaccuracy. Normalized OPSpecs charts are presented to permit a more general assessment of the analytical performance required with commonly used QC procedures. PMID- 1623587 TI - Proficiency testing as a regulatory device: a CAP perspective. AB - The history and development of the proficiency testing programs of the College of American Pathologists are reviewed. Important considerations of external surveys include target value assignment and determination of acceptable ranges. "Blind" proficiency testing and on-site evaluation provide alternative methods of laboratory evaluation but are limited by practical logistics. PMID- 1623588 TI - Limitations of proficiency testing under CLIA '67. AB - Proficiency testing (PT), recognized as a quality-assurance (QA) and quality improvement tool, also has become the cornerstone of the Health Care Financing Administration's (HCFA) regulatory strategy under the revised Clinical Laboratory Improvement Act of 1967 (CLIA '67) and the proposed Clinical Laboratory Improvement Amendments of 1988 (CLIA '88). Use of PT as a regulatory tool corrupts it for things it can do better. PT as a primary regulatory strategy has severe limitations. We explore the nature of these limitations and their implications for clinical laboratories as they impact on the long-term success of HCFA's approved regulatory PT programs in 1991 and beyond, and CLIA '88 PT, which is to be implemented in 1994. PMID- 1623589 TI - Regulation of proficiency testing under the March 14 rule. PMID- 1623590 TI - Review of actual proficiency-testing performance under CLIA '67 (March 14, 1990) rules: perspective from the first year's data. AB - Under the Clinical Laboratory Improvement Act of 1967 the Health Care Financing Administration's proficiency-testing requirement applies to approximately 12,000 hospital, reference, and large-clinic laboratories in the United States. The Wisconsin State Laboratory of Hygiene is approved by the Health Care Financing Administration to provide proficiency testing in all specialties and subspecialties. The focus of the program is to provide highly specialized service and support to a limited number of participants in order to assess intralaboratory performance correctly. We report the findings over the four proficiency-testing events in 1991 for the subspecialty of routine chemistry, which serves approximately 470 participants. Failure rates for individual analytes on single proficiency testing events ranged from 0% to 13%. After four events or one year, if the mandated evaluation criteria and failure rules were strictly applied, as many as 11% of the laboratories could have found themselves involuntarily suspended from offering all routine chemistry testing. PMID- 1623591 TI - Proficiency testing linked to the national reference system for the clinical laboratory: a proposal for achieving accuracy. AB - I propose using proficiency testing (PT) to achieve one of the important goals of CLIA: accurate and reliable clinical testing. Routine methods for the clinical laboratory are traceable to Definitive (DM) or Reference Methods (RM) or to Methodological Principles (MP) through a modification of the National Reference System for the Clinical Laboratory. PT is the link used to monitor consistent field performance. Although PT has been effective as a relative measure of laboratory performance, the technical limitations of PT fluids and of routine methods currently in use make it unlikely that PT alone can be used as a reliable measure of laboratory accuracy. Instead, I recommend calibration of routine systems through correlation to DM, RM, or MP with use of patients' specimens. The manufacturer is in the best position to assume this responsibility because of also being responsible for consistent, reliable product. Analysis of different manufactured batches of reagent would be compared with predetermined goals for precision and accuracy, as illustrated with data from product testing of Kodak Ektachem clinical chemistry slides. Adoption of this proposal would give manufacturers of PT materials, manufacturers of analytical systems, PT providers, and government agencies time to understand and resolve sources of error that limit the utility of PT for the job required by law. PMID- 1623592 TI - The impact of new regulations on laboratory testing in physicians' offices. AB - The reaction of the clinician to the specter of regulation of any part of his or her practice mirrors the reaction of the laboratorian to the implementation of Medicare and Clinical Laboratory Improvement Amendments legislation in 1965 and 1967, respectively. Whether the regulatory burdens that will be visited upon these laboratories are justified or necessary is arguable; the fact of the upcoming regulation is not. The volume and breadth of testing in physicians' office laboratories (POLs) has increased exponentially since passage of the Diagnosis Related Group legislation by Congress in 1983, an increase made possible by remarkable developments in technology. State regulatory initiatives and private accrediting agencies have been perceived as being inadequate to prevent the proliferation of poorly controlled testing in the nontraditional laboratory environment. The testing menu of a given POL varies according to the scope of clinical services offered; the size of the practice group; the funding available for equipment and personnel acquisition; and the general availability of hospital, reference, and consultative laboratory services. Physicians who offer laboratory services as part of their practices must now prepare their laboratories to meet whatever requirements are mandated by regulation. This will include acquisition of trained personnel, improvement of instrumentation and methodologies, participation in proficiency testing, establishment of comprehensive quality-assurance programs, and adequate documentation of laboratory services. Organized medicine should devote its energies to assisting with needed educational processes to assure the survival of POLs. PMID- 1623593 TI - The impact of legislation on future technology development. AB - In this paper I examine some of the factors influencing technology development and attempt to explain whether CLIA '88 enhances the opportunities or exacerbates the problems for U.S.-based technology development. The viewpoint I express is concentrated on the clinical chemistry segment of the diagnostics arena. PMID- 1623594 TI - Dependence of free thyroxine estimates obtained with equilibrium tracer dialysis on the concentration of thyroxine-binding globulin. AB - Some equilibrium dialysis determinations of free thyroxine (T4) vary directly with thyroxine-binding globulin (TBG) concentration. This apparent TBG dependence has been limited to methods involving radiolabeled T4 added to the dialysis system (tracer dialysis). In this study we compared tracer dialysis with direct dialysis for determining free T4 and obtained the following results (mean +/- SD) for patients with hypothyroxinemia of nonthyroidal illness (23.8 +/- 10.7 vs 24.2 +/- 10.9 pmol/L, P greater than 0.8), patients with congenital TBG deficiency (11.4 +/- 2.2 vs 16.2 +/- 7.1 pmol/L, P greater than 0.05), normal control subjects (32.7 +/- 6.5 vs 18.5 +/- 5.8 pmol/L, P less than 0.001), and pregnant women (31.2 +/- 8.7 vs 12.1 +/- 2.6 pmol/L, P less than 0.001). Direct dialysis determinations were independent of TBG and total T4. Tracer determinations were greater than direct determinations in normals, a discrepancy that increased in pregnancy. Tracer determinations correlated significantly with total T4 and TBG concentrations (P less than 0.001). TBG and total T4 dependence in the tracer method was attributable to small overestimations of the free fraction of T4. Similar overestimations multiplied by increasing total T4 concentrations resulted in greater errors. Relative to results for normal sera, the tracer method overestimated free T4 when total T4 was increased and underestimated free T4 when total T4 was decreased. PMID- 1623595 TI - Failure of common glycation assays to detect glycation by fructose. AB - Serum albumin was modified by in vitro glycation with either fructose or glucose, to see whether the common clinical assays for glycation were able to detect both fructose- and glucose-induced changes in protein structure in diabetes. Although fluorescence measurements showed that fructose causes far more protein damage than glucose, neither serum fructosamine (SFA) nor phenylboronate affinity (PBA) glycation assays reflected these changes. The SFA method implied that fructose causes only about 5% of the glycation induced by glucose; with PBA the proportion was 25%. The thiobarbituric acid- and periodate-based assays also greatly underestimated the true extent of fructation. We discuss these discrepancies with respect to the underlying chemistry, emphasizing the difference between aldehydic and ketonic Amadori products (exemplified by fructose and glucose derivatives, respectively). The implications for detecting fructose-induced secondary diabetic complications are also discussed. PMID- 1623596 TI - Homocysteine export from erythrocytes and its implication for plasma sampling. AB - The concentration of free and total homocysteine in plasma increases in time if blood is stored uncentrifuged after sampling. The increase is temperature dependent and the maximal increase in total plasma homocysteine at 37 degrees C was 3.0 mumol.L-1.h-1. Even at 4 degrees C there is a substantial increase, particularly of free plasma homocysteine. Plasma glutathione, cysteinylglycine, and gamma-glutamylcysteine also show an increase in time if whole blood is stored, whereas cysteine decreases. We show that the erythrocytes are responsible for most of the increase in plasma homocysteine and suggest that homocysteine is derived from adenosylmethionine-dependent protein carboxymethylations in the cells. We conclude that strict sampling conditions are necessary when plasma homocysteine and especially its free fraction are assayed. PMID- 1623597 TI - Dynamic relation between reduced, oxidized, and protein-bound homocysteine and other thiol components in plasma during methionine loading in healthy men. AB - We used a newly developed procedure to determine reduced, oxidized, and protein bound forms of homocysteine, cysteine, cysteinylglycine, and glutathione to measure the plasma concentrations of these species during methionine loading in six young healthy men with normal fasting concentrations of plasma homocysteine and cysteine. The methionine loading induced a transient increase in total homocysteine, which peaked after approximately 6-8 h. All six subjects showed a concurrent significant increase in reduced homocysteine and cysteine, which peaked 2 h after loading, and a rapid decrease in protein-bound cysteine and cysteinylglycine. The concentration of reduced cysteinylglycine was not altered. Plots of protein-bound cysteine and cysteinylglycine vs total homocysteine formed hysteretic loops, showing a time-dependent relation between these analytes. After the initial decrease, protein-bound cysteine and cysteinylglycine showed a slight, transient increase. From 12 to 24 h after loading, protein-bound cysteine approached preloading concentrations in two subjects and declined further in four subjects. The response pattern was similar for cysteine and cysteinylglycine in each subject. Simple displacement could not account for these effects, which suggests that plasma homocysteine may affect the disposition of other thiols through complex mechanisms. The presence of reduced homocysteine and the dynamic relation that exists between homocysteine, cysteine, and related compounds in plasma should be taken into account when evaluating plasma homocysteine as an indicator or causative agent of human disease. PMID- 1623598 TI - Serum adenosine deaminase: isoenzymes and diagnostic application. AB - Human adenosine deaminase (ADA; EC 3.5.4.4) consists of three isoenzymes: ADA1, ADA1+CP, and ADA2. We developed an electrophoretic technique to distinguish between these three isoenzymes. The isoenzyme pattern was studied in tissue and cell homogenates, as well as in serum from normal subjects and from patients with increased serum ADA who had either hepatitis, infectious mononucleosis, tuberculosis, pneumonia, rheumatoid arthritis, or acute lymphoblastic leukemia (ALL). The highest ADA activity was found in lymphocytes and monocytes. ADA2 could be detected only in monocytes (18% of total ADA activity). It was also the predominant isoenzyme in the sera of controls and all disease groups, except for ALL--the only condition evaluated that is not of an inflammatory nature. We conclude that serum ADA reflects monocyte/macrophage activity or turnover in most diseases studied. The exception is ALL, where serum ADA most probably originates from lymphocyte precursors. PMID- 1623599 TI - Temperature effects on free-thyroxine measurements: analytical and clinical consequences. AB - We compared the analytical and clinical performance of two free-thyroxine (FT4) assays--a solid-phase radioimmunoassay, Spectria, and a time-resolved fluoroimmunoassay, Delfia, both of them two-step methods--with the performance of a direct radioimmunoassay, Nichols, to measure FT4 concentration in equilibrium dialysate of undiluted serum. The three assays showed comparable analytical performance. We tested clinical utility in sera from 135 healthy subjects with and without thyroxine-binding abnormalities and in 61 patients with and without thyroidal illnesses. We found significant differences for FT4 measured by different assays in sera from the same euthyroid patients. To explain the differences, we studied the influence of temperature on performance and calibration. Most important was the neglected fact that the association constant for the binding of thyroxine to thyroxine-binding globulin decreases when the temperature rises from 20 to 37 degrees C, causing a doubling of FT4. The two step assays, if performed at room temperature without a well-defined calibration, can give misleading FT4 concentrations. This is the case when sera from patients with thyroxine-binding abnormalities are measured against kit standards, made up in normal human sera. If an assay is to reflect the in vivo FT4 concentration at body temperature in all types of samples, it should be performed at body temperature. For practical reasons 37 degrees C is recommended, and reference values should be defined at 37 degrees C. The same might be valid for other free hormone assays. PMID- 1623600 TI - Design and preliminary performance characteristics of a newly proposed reference cell for ionized calcium in serum. AB - A novel flow-through design for a calcium ion-selective liquid membrane and half cell is proposed. The membrane is based on a neutral carrier for calcium and has the same quantitative chemical composition as that used in most commercial analyzers for ionized calcium (iCa2+). The membrane and half-cell follow the specifications in the Stage 1, Draft 4 document for a Reference Method for iCa2+ of the IFCC Expert Panel on pH, Blood Gases, and Electrolytes. Measurements of iCa2+ in serum with this cell confirm prior observations that protein adsorption on the membrane surface causes a rapid but reversible shift in the cell calibration signal and possible systematic errors in the measurement of iCa2+ in serum. When the protein adsorption phenomenon is maintained at equilibrium during calibrations and sample measurements, the new cell can be used to reproducibly assign iCa2+ concentrations to serum pools. These calibrated pools may then be used as reference materials and to resolve the biases known to exist among commercial iCa2+ analyzers. PMID- 1623601 TI - Changes in alkaline phosphatase and 5'-nucleotidase multiple forms after surgical management of biliary obstruction. AB - Serial measurements of alkaline phosphatase and 5'-nucleotidase multiple forms in two patients undergoing surgical procedures to release biliary obstruction suggested an inverse relationship between high-M(r) isoforms and serum bile acids concentrations. Furthermore, the study of several groups of patients with cholestatic disorders confirmed this inverse correlation. Mechanisms responsible for these observations are discussed. PMID- 1623602 TI - Measuring albumin and calcium in serum in a dual test with the Hitachi 704. AB - We describe a method for simultaneously determining albumin, by using bromcresol purple, and calcium, by using Arsenazo III, in the same analytical cuvette on the Hitachi 704. Both assays agree well with accepted procedures. The standard curves for the albumin and calcium assays are linear from 0 to 60 g/L and 0 to 5.0 mmol/L, respectively. Calibration is stable for 7 days with use of open reagent in the instrument. Both assays are unaffected by hemoglobin less than or equal to 5 g/L and Intralipid less than or equal to 4 g/L; calcium is unaffected by bilirubin less than or equal to 600 mumol/L. PMID- 1623603 TI - Interassay variability of immunometric methods for thyrotropin in an external quality assessment survey: evidence that functional sensitivity is not always adequate for clinical decisions. AB - We investigated the ability of current immunometric methods for thyrotropin (TSH; thyroid-stimulating hormone) to distinguish between low-normal and subnormal hormone concentrations by using the data from an external quality assessment (EQA) survey in 1990. We computed the interassay (between-run) precision profiles from results from 101 laboratories, which used the five most popular kits in the survey; during the control period (one year) each laboratory assayed 4 EQA pools distributed (as hidden replicates) in five occasions. The interassay CV was relatively low (9-13%) for three pools in the normal TSH range (greater than 0.8 milli-int. unit/L) but markedly higher (30-40%, except for one more precise kit) in the subnormal range (0.2 milli-int. unit/L). We calculated the effect of the between-run variability on the diagnostic accuracy (discrimination between normal and subnormal values) for three representative TSH concentrations: 0.2, 0.4, and 0.5 milli-int. unit/L (0.3 milli-int. unit/L was considered the lower normal limit). The three concentrations were reasonably discriminated (P less than or equal to 5%), and only one kit showed a between-run CV less than 18% at 0.2 milli int. unit/L. For the other four less-precise kits, only the higher TSH value (0.5 milli-int. unit/L) could be classified with an acceptable diagnostic reliability. With the most precise kit, one can distinguish two TSH concentrations in the 0.3 0.5 milli-int. unit/L range that differ by at least 30%; with the other kits, differences greater than 50-60% are needed for reliable discrimination. Thus many laboratories fail to achieve the functional sensitivity of a second-generation assay, even if they use immunometric methods. TSH assays with a better interassay precision in the low concentration range are needed. PMID- 1623604 TI - Detection of hepatitis B virus DNA in serum by a nonisotopic hybridization technique. AB - We developed a nonisotopic technique, Hepagene, for measuring hepatitis B virus (HBV) DNA in human serum by using a sulfonated probe that is detected by a sandwich immunoenzymatic reaction. The detection limit, determined by serum dilution tests, was 2.5 ng/L. The precision of the Hepagene test was demonstrated by the accurate reproducibility observed for low (3 ng/L) and medium (38 ng/L) concentrations of HBV DNA assayed in 24 different series. Specificity was established by assaying HBV DNA in sera from 98 patients by the Hepagene technique or by a solution hybridization assay with an 125I-labeled probe. Results by both techniques agreed for 94 sera (96%), with 68 being concordant for HBV DNA negativity and 26 for positivity. HBV DNA titers assayed by both methods also agreed. Hepagene represents the first nonisotopic HBV DNA assay involving a sulfonated probe and with performance characteristics equivalent to those of classical radioactive hybridization techniques. PMID- 1623605 TI - Effects of temperature on optical absorbance spectra of oxy-, carboxy-, and deoxyhemoglobin. AB - The optical absorbance spectra of oxy-, carboxy-, and deoxyhemoglobin were recorded at wavelengths from 479 to 651 nm and at temperatures of 20, 30, and 40 degrees C. As noted in earlier reports, a major effect of lowering the temperature was an increase in the absorptivities at or near the absorbance maxima. However, at other wavelengths, reducing the temperature increased, decreased, or caused no change in absorbance. At wavelengths where temperature induced shifts did occur, the absorbance change appeared to be a linear function of temperature. Unlike previous reports, the data presented here are quantitative and thus can be used to predict temperature-induced errors in spectrophotometric measurements of the relative concentrations of these hemoglobin species. Examples are given of the error that would occur in a widely used CO-Oximeter, the IL482, if it were not temperature controlled. Thus, the data presented here should be particularly useful to the operators and designers of spectrophotometric instruments such as oximeters, CO-Oximeters, and hemoglobinometers. PMID- 1623606 TI - Testing for creatine kinase and creatine kinase-2 in Ontario: reference ranges and assay types. AB - In 1991, 246 and 136 Ontario laboratories performed total creatine kinase (CK; EC 2.7.3.2) and creatine kinase-2 (CK-2) assays, respectively. A questionnaire mailed to these laboratories requested information about the types of assay used, the origin of their reference ranges, and the source of their instruments and reagents. All laboratories used current test formulations for CK, although seven laboratories did not assay at 37 degrees C. For CK, 69% of all laboratories reported different upper reference limits for men and women (5th-95th percentiles: 160-250 and 115-215 U/L, respectively); 31% reported similar ranges for both sexes. Fifty-six percent derived their own ranges; the remainder used either kit inserts or literature references, and nearly 60% of this latter group claimed to have validated these suggested ranges before use. For 6% of all laboratories, their pediatric ranges were similar to their adult ranges. For CK 2, only 32% used their own reference range; the remainder used kit inserts or literature references, but only 49% of this group validated these ranges before use. Reference limits (5th-95th percentiles) for CK-2 were as follows: activity 6 24 U/L; fraction of CK, 0.022-0.06; and, for mass assays, 5-10 micrograms/L and relative index 0.015-0.04. PMID- 1623607 TI - Colorimetric determination of potassium in plasma and serum by reflectance photometry with a dry-chemistry reagent. AB - We evaluated a colorimetric assay of potassium in plasma and serum with the Boehringer Mannheim Reflotron reflectance photometric analyzer, which is designed for near-patient testing in hospitals and physicians' offices. This potassium method does not require calibration or instrument maintenance by the operator. Analysis of 30 microL of plasma or serum takes approximately 140 s. Within-day imprecision (CV) was 1.0-1.2%. Total CVs over a 1-month period were 1.0-1.4%. Patients' results from the Reflotron correlated well with those from the IL 643 flame photometer and the Beckman Synchron CX3 ion-selective electrode methods. The accuracy of Reflotron values was also verified with Standard Reference Material 956 from the National Institute of Standards and Technology. PMID- 1623608 TI - Sensitive, direct procedures for simultaneous determinations of iron and copper in serum, with use of 2-(5-nitro-2-pyridylazo)-5-(N-propyl-N sulfopropylamino)phenol (nitro-PAPS) as ligand. AB - We developed a direct, simple, and sensitive procedure for the simultaneous colorimetric assay of iron and copper in serum, using sodium dodecyl sulfate ascorbic acid to dissociate iron and copper from transferrin and ceruloplasmin, respectively. We also use a new water-soluble reagent, 2-(5-nitro-2-pyridylazo)-5 (N-propyl-N-sulfopropylamino)phenol disodium salt (nitro-PAPS) and thioglycolic acid to eliminate interference from copper in the measurement of iron. Within- and between-run precisions of the present method were 2.5-2.8% for iron and 1.8 4.6% for copper. The proposed method is susceptible to interference by hemoglobin and lipemia, especially for the iron assay. Linear-regression analyses of results of the proposed method with those of the bathophenanthroline method for iron and of the atomic absorption spectroscopic method for copper correlated well (r = 0.996, Sy/x = 0.73 and r = 0.959, Sy/x = 1.11, respectively). PMID- 1623609 TI - Immunoturbidimetry of apolipoprotein B in lyophilized human serum pools using primary standard. PMID- 1623610 TI - Error detection of high concentrations of endogenous free glycerol in determination of serum triglyceride with the TBA-80S automated discrete analyzer. PMID- 1623611 TI - Impact of inhibition of angiotensin-converting enzyme on urinary excretion of proteins in chronic heart failure. PMID- 1623612 TI - Multiple occurrence of macro creatine kinase in one family. AB - We measured creatine kinase (CK, EC 2.7.3.2), CK-MB isoenzyme activity and mass concentration, and distribution of CK isoenzymes (by electrophoresis) in serum from five members of one family. The mother and two young children showed CK-IgG complexes in their sera. The concentration of the CK-IgG complexes in the children decreased over time, suggesting that the complex involved maternal IgG and had been transferred across the placenta from the mother to her children. PMID- 1623613 TI - Actual ionized calcium (at actual pH) vs adjusted ionized calcium (at pH 7.4) in hemodialyzed patients. PMID- 1623614 TI - Atypical electrophoretic and isoelectrophoretic patterns of neutrophil alkaline phosphatase in a case of subacute myelomonocytic leukemia. PMID- 1623615 TI - Caffeine concentrations in adult patients chronically taking theophylline. PMID- 1623616 TI - Variability of glucose tolerance test in pregnancy diminished by use of a glucose polymer. PMID- 1623617 TI - "Half-life" is erroneously used to describe the disappearance of erythrocytes and hemoglobin from the circulation. PMID- 1623618 TI - Rapid diagnosis of mitochondrial mutation at position 11778-associated Leber hereditary optic neuropathy. PMID- 1623619 TI - Multiple serum protein abnormalities in carbohydrate-deficient glycoprotein syndrome: pathognomonic finding of two-dimensional electrophoresis? PMID- 1623620 TI - Increases in CA-125 concentrations in children. PMID- 1623621 TI - Familial spastic paraplegia with neuropathy and poikiloderma. A new syndrome? AB - We report a case study spanning three generations of familial spastic paraplegia, distal amyotrophy and poikiloderma. This study is the first description of an association between these three disorders. The gait disorder, the sensory and motor involvement and the skin disorder coincide in all the affected members, suggesting autosomal dominant inheritance with complete penetrance. PMID- 1623622 TI - 20 p duplication as a result of parental translocation: familial case report and a contribution to the clinical delineation of the syndrome. AB - We report two related patients, presenting duplication 20p, with a characteristic phenotype including normal growth pattern, mental and psychomotor retardation, reduced motor coordination, poor language development, round face and prominent cheeks, vertebral and dental anomalies, and renal malformations. Familial chromosome analysis showed a balanced translocation t(20;21)(p11;q22) in three members of the family. These cases, together with those previously reported in the literature, allow us to make a better delineation of the duplication 20p syndrome, identifying more clearly the symptoms that must be considered as characteristic of this clinical picture. PMID- 1623623 TI - Identical twins with an autosomal recessive form of spondylocostal dysostosis. AB - A form of spondylocostal dysostosis, marked by multiple vertebral clefts, costal bifurcation, and fusion was observed in identical male twins whose parents were first cousins. The lack of previous anomalies in the family, the high degree of parental inbreeding and the absence of deformities in a 3-year-old brother indicated an autosomal recessive mode of inheritance. PMID- 1623624 TI - A syndrome of progressive sensorineural deafness and cataract inherited as an autosomal dominant trait. AB - In 1982, Nadol & Burgess reported a new syndrome of cataract and progressive sensorineural hearing loss, inherited in an autosomal dominant fashion. Extensive histopathologic studies of the inner ear of the proband revealed severe cochleosaccular degeneration. No other sporadic or familial cases of such a genetic syndrome have subsequently been described. We report here a second family in which the syndrome of cataract and progressive sensorineural deafness is observed in eight members, and is inherited according to an autosomal dominant pattern. PMID- 1623625 TI - Hair-nail dysplasia--a new pure autosomal dominant ectodermal dysplasia. AB - An apparently hitherto undescribed pure ectodermal dysplasia of the tricho onychic subgroup is described. Its cause is an autosomal dominant gene with complete penetrance and variable expressivity. Differential diagnosis considered 18 conditions belonging to the same subgroup, as well as Clouston syndrome. This report increases the number of conditions of the tricho-onychic subgroup to 19, and the total number of ectodermal dysplasias to 155. PMID- 1623626 TI - Intrachromosomal insertion of chromosome 7. AB - A direct intrachromosome insertion of chromosome 7 is described, and previous reports of intrachromosomal insertions are listed. All others were ascertained through a phenotypically abnormal proband. Ours is the first presenting with multiple pregnancy losses. Since the risk of chromosomally abnormal liveborns is appreciable, prenatal diagnosis should be made available to known carriers of chromosome insertions. PMID- 1623627 TI - Differentiated recurrence risk estimations in the Prader-Willi syndrome. AB - The Prader-Willi syndrome usually occurs sporadically. About 60% of the patients show a chromosomal deletion of proximal 15q. There are only a few reports on familial recurrence. Two previous estimates give either a low but recognizable recurrence risk of 1.6% or a risk of less than 0.1%. The inconsistency is obviously due to differences in the stringency of the diagnostic criteria used and to different modes of ascertainment of cases. This gave rise to a review of the literature, leading to the following suggestions: (1) A deletion at 15q has not been found in a familial case of PWS, except in those cases where del(15q) is due to familial structural chromosome rearrangements. Hence, with de novo deletion, the recurrence risk should be nearly zero. (2) In cases with familial translocation, risk estimates depend on the variable nature of the familial chromosome mutation. (3) If only one child is affected and has no deletion at 15q, this may be a sporadic or an isolated familial case. For this situation I estimated an overall recurrence risk of 0.4%. (4) If two or more sibs are affected, I consider a risk of 50% that the next sib may also be affected. This estimate reflects the observed segregation ratio and is in accordance with the proposed genomic imprinting model in the etiology of PWS. Prenatal cytogenetic diagnosis in a pregnancy at risk for PWS is hampered since del(15q) is almost exclusively found in sporadic cases. Hence, this method is limited to those very rare cases where del(15q) is due to familial structural chromosome rearrangements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623628 TI - Cytogenetic and dermatoglyphic findings in a familial case of hypomelanosis of Ito (incontinentia pigmenti achromians). AB - Cytogenetic and dermatoglyphic investigations were performed in a mother (M.B.) and her daughter (D.B.), who were both suffering from hypomelanosis of Ito (incontinentia pigmenti achromians; HI). Whereas quite normal chromosomal results could be obtained after culture of peripheral lymphocytes, a diploid/tetraploid mosaicism (46,XX/92,XXXX) was found in cultured skin-fibroblasts derived from a hypopigmented skin area of M.B., with a slowly decreasing tetraploidy rate in the course of passaging: #2 23%, #5 11%, #11 and #14 6% and #18 and #21 2%. In cultures of normally pigmented skin, only single tetraploid cells could be detected. Dermatoglyphic examinations in both patients showed single transverse creases, a high number of secondary creases and a longitudinal alignment of the main line A bilaterally, and there was a tricentric fingertip pattern on the right digit III of M.B., i.e. a pattern which occurs very seldom in human beings. The results are discussed in respect to the clinical-diagnostic overlap of HI and incontinentia pigmenti Bloch-Sulzberger. PMID- 1623629 TI - Population variation and genetics of plasma homocyst(e)ine level. AB - A high level of plasma homocyst(e)ine (H(e)) has been reported to be an independent risk factor for coronary heart disease (CHD), at least in some populations. We have determined the H(e) concentration in the plasma of two series of Norwegians in order to establish a baseline for future analysis of people with CHD. The mean sex- and age-adjusted homocyst(e)ine level was 10.6 (range 4.84-29.88) in one series and 10.5 (range 3.76-40.57) in the other. The H(e) level appeared to be independent of other proven or potential risk factors or protective factors with respect to CHD. The intraclass correlation coefficient in monozygotic (MZ) twins is a (possibly inflated) estimate of heritability. We have examined two series of MZ twins. The intraclass correlation coefficient was significant in both series. In one series, the Pearson correlation coefficient was 0.53 and the Kendall correlation coefficient 0.38. In the other, the values were 0.56 and 0.46, respectively. We conclude that in the population examined, H(e) levels exhibit significant heritability. PMID- 1623630 TI - Retinitis pigmentosa, AD type I: exclusion of linkage to D3S47 (C17) in a large South African family of British origin. AB - Linkage analysis has been performed on a large South African family of British origin in which 39 persons in 6 generations had early onset Type I autosomal dominant retinitis pigmentosa (ADRP). Tight linkage was excluded between the disease and the D3S47 locus on chromosome 3. This finding is further evidence for genetic heterogeneity in ADRP. PMID- 1623631 TI - Human beta-mannosidosis: a 3-year-old boy with speech impairment and emotional instability. AB - Beta-mannosidosis is a recently described inherited disorder with predominantly neurological signs and symptoms as the major manifestations of the disorder. The heterogeneous manifestations of the disease have been presented in seven previous patients. We describe a further case of European descent with an infantile onset of the disease, with the features of speech impairment as the first symptom. Beta mannosidase activity was completely deficient in the patient and a heterozygote level was found in the parents. In addition, mannosyl-N-acetylglucosamine was identified in the patient's urine in keeping with the diagnosis of beta mannosidosis. PMID- 1623632 TI - Chromosomal aberrations in Sotos syndrome. PMID- 1623633 TI - Chemical design of peripherally acting compounds. AB - 1. Some guanidines, related in structure to mianserin and to 2-methyl-1,2,9,13b tetrahydro-3H-dibenz[c,f]imadazo[1,5a] azepin-3-imine hydrobromide (WAL 801), have been synthesized and shown to be peripherally acting 5-HT2 antagonists. Structurally related compounds but not bearing a charged ionic group have been shown to have central activity. 2. Computer-aided molecular modelling has been used to establish a 5-HT2 pharmacophore. 3. The principle of exclusion from the CNS by incorporating a highly polar group to a biologically active molecule has been extended to the design and synthesis of a peripherally acting analgesic. PMID- 1623634 TI - The evolution of hypertensive therapy. AB - 1. During the past 30 years many antihypertensive agents, acting at differing levels on the mechanisms controlling arterial blood pressure, have been introduced. 2. Whereas the usefulness of early drugs was limited by side effects, the discovery of successive classes of agents has resulted in the gradual introduction of drugs causing fewer adverse effects with consequent improvements in patient compliance. 3. The recent appearance of angiotensin II antagonists and potassium channel openers, together with increased knowledge of the roles played by atrial natriuretic factor and endothelial cell-derived autacoids in control of vascular tone, hold prospects for still further improvements in therapy. PMID- 1623635 TI - Buprenorphine and gastrointestinal transit in rats: effect of naloxone on the biphasic dose-response curve. AB - 1. Buprenorphine (0.01-10 mg/kg, subcutaneous [s.c.]) slowed the passage of a charcoal meal along the gastrointestinal tract in rats. The dose-response relationship was U-shaped. 2. When rats were pretreated with naloxone (0.30 mg/kg, s.c.), both the descending and ascending components of the buprenorphine dose-response curve were displaced to the right. 3. Buprenorphine-induced delay of transit was maximal at a dose of 0.10 mg/kg. In rats pretreated with naloxone, a 30-fold higher dose of buprenorphine was required for a comparable peak effect. 4. Moderate-high doses of buprenorphine may be acting on a functionally related binding site which non-competitively inhibits the usual buprenorphine-mu opioid receptor interaction. PMID- 1623636 TI - An industrial approach to drug discovery: a pharmacologist's eyeview. AB - 1. The pressures on the pharmaceutical industry to produce novel, safe and effective therapeutic agents have provoked management to rethink the way in which drug discovery is undertaken. 2. Advances in drug therapy are likely to come from the application of new technologies and leading-edge science, perhaps in collaboration with academia. 3. Close collaboration between biologists and medicinal chemists is a proven way to discover new products. 4. The complexity of the modern industrial discovery process, due to the interaction of many disciplines, requires matrix-style management. 5. The early demonstration of efficacy in human subjects is considered essential for providing feedback to the basic scientists about the validity of hypotheses, and the relevance of the methods utilized, as well as whether a decision should be allowed to advance to full development. PMID- 1623637 TI - Government initiatives in the development of a pharmaceutical industry in Australia. AB - Government policy recognizes that the purchasing power of the government, through the Pharmaceutical Benefits Scheme, has suppressed prices and returns to the pharmaceutical industry in Australia, and that research, development and export activities have been low. The factor (f) scheme is designed to provide some pricing relief to those companies willing and able to undertake particular industry development activities. This scheme, together with the other changes implemented by the government, will result in the restructuring and development of the pharmaceutical industry in Australia. PMID- 1623638 TI - AMRAD: the first 4 years. AB - 1. AMRAD (Australian Medical Research and Development) Corporation is a Melbourne biomedical research and development based pharmaceutical company that has successfully completed the first 4 years of its activities. 2. The success of the company is a result of a number of factors including the association with world class medical research institutes, adequate seed capital and sound management skills. PMID- 1623639 TI - Symbiotic relationship between a research institute and a pharmaceutical company: the Baker Institute/Glaxo Australia story. AB - 1. The Baker Medical Research Institute is a non-profit, charitable institution to advance knowledge and solve problems in the area of cardiovascular medicine. This allows scientists to collaborate within a critical mass and be flexible in their approach to research. 2. The Institute has interactions with the pharmaceutical industry at three levels: (i) contract research on a specific molecule; (ii) clinical trials; and (iii) collaborative basic research agreements. 3. The Glaxo Australia-Baker Medical Research Institute Agreement is for curiosity driven research in specified areas of vascular pharmacology of interest to Glaxo Group Research. 4. The relationship between universities, research institutes and the pharmaceutical industry is discussed in terms of the starting point for drug development. 5. The enormous cost (US$100 million), lead time (10 years) and uncertainty of a successful profitable drug are compelling reasons why an independent pharmaceutical company is unlikely to succeed in Australia today. PMID- 1623640 TI - Cardiovascular sensitivity changes to eicosanoids in rats with experimentally induced diabetes mellitus. AB - This paper attempts to provide a short review of the evidence for: 1. Increased platelet production of thromboxane A2 and reduced vascular production of prostacyclin in the human and also animal models of diabetes. 2. Reduced depressor responsiveness to arachidonic acid of anaesthetized alloxan- and streptozotocin-induced diabetic rats. 3. Enhanced constrictor responsiveness to arachidonic acid in blood-perfused hindquarters of alloxan-induced diabetic rats. 4. Potentiation by the thromboxane A2-mimetic, U46619, of constrictor responses to 5-hydroxytryptamine in Krebs'-perfused hindquarters and kidneys of both control and alloxan-induced diabetic rats. 5. Alterations during diabetes in production of, and responsiveness to, eicosanoids may contribute to the cardiovascular changes which occur in this disease. PMID- 1623641 TI - The atherogenic effect of lupus sera: systemic lupus erythematosus-derived immune complexes stimulate the accumulation of cholesterol in cultured smooth muscle cells from human aorta. AB - The influence of systemic lupus erythematosus (SLE) patients' sera on lipid accumulation in the cultured smooth muscle cells (SMC) from unaffected human aortic intima was examined. It was demonstrated that the cholesterol uptake in the SMC cultured in the presence of SLE sera is 1.5- to 6-fold higher than in the cells cultured with normal human sera (NHS) obtained from healthy donors. Incubation of the SMC with circulating immune complexes (CIC) isolated from lupus sera by precipitation with 2.5% polyethylene glycol 6000 (PEG) caused a 3- to 4 fold rise in the intracellular cholesterol level. The atherogenic effect of lupus sera, as well as isolated CIC, strongly correlated (r = 0.98) with the low density lipoprotein (LDL) content in the PEG-precipitated CIC. The cholesterol level in cultured SMC also increased 2- to 3-fold when growth medium was supplemented with LDL, DNA, and anti-DNA autoantibodies (IgG) affinity isolated from lupus sera. Using immunofluorescent staining, it was shown that the addition of a DNA-anti-DNA IgG mixture to the growth medium, together with NHS, stimulated LDL incorporation in the SMC. The results of double-label staining suggest the formation of LDL-DNA-IgG complexes which seem to be entrapped in cells more actively than free LDL. The composition of PEG-precipitated CIC was studied by electrophoresis and immunoblotting. Significant amounts of apolipoprotein B, as well as low molecular weight DNA and immunoglobulins, were found in SLE-derived CIC. The data obtained suggest that the atherogenic effect of human lupus sera in vitro is generally due to the appearance of LDL-containing immune complexes. Different mechanisms possibly involved in the lupus atherogenesis are discussed. PMID- 1623642 TI - Prostaglandin E2 induces apoptosis in immature normal and malignant B lymphocytes. AB - The purpose of this research was to determine whether prostaglandin E2 (PGE2), a major product of macrophages which can kill certain murine B cell lymphomas, induces death by a necrotic mechanism or by an alternate pathway called apoptosis. CH31 is a phenotypically "immature" B cell lymphoma which resembles immature neonatal B cells in its susceptibility to killing by reagents which cross-link surface immunoglobulin (sIg). In the present study we first show that PGE2, but not the closely related prostanoid, PGF2 alpha, kills CH31 lymphoma cells. In contrast, CH12, a phenotypically "mature" lymphoma which is not negatively affected by sIg cross-linking, is not induced to die after exposure to PGE2. Agarose gel electrophoresis demonstrated that the DNA of PGE2-treated CH31, but not CH12 cells, is cleaved into characteristic 200 base pair oligonucleosomal fragments indicative of an apoptotic mechanism of death. However, a necrotic form of death, indicated by random DNA cleavage which produces a smear following electrophoresis, could be induced by treatment of CH12 or CH31 with anti-class II MHC antibodies and complement. The apoptotic mechanism of CH31 cell killing by PGE2 was confirmed using scanning electron microscopy which demonstrated the unique membrane blebbing and bubbling pathognomonic of this form of death. Finally, using a recently devised flow cytometric method to study apoptosis in heterogeneous cell populations, we compared the ability of anti-IgM, PGE2, or PGF2 alpha to induce apoptosis in B lymphocytes from neonatal or adult mice. Anti IgM, and to a lesser extent PGE2, but not PGF2 alpha, induces apoptosis in a fraction of neonatal B cells. None of these treatments induced cell death in B lymphocytes from mature mice. Overall, these observations suggest that PGE secreting cells such as macrophages, which inhabit the B cell microenvironments of lymphoid organs, may eliminate a subset of immature B lymphocytes and may be important in controlling the spread of PGE-sensitive malignant B lymphoma cells. PMID- 1623643 TI - Immune complexes and antibody levels in blisters over human leprosy skin lesions with or without erythema nodosum leprosum. AB - Erythema nodosum leprosum (ENL) is a serious complication of lepromatous leprosy, affecting skin and peripheral nerves in a large percentage of these patients, and is presumed to result from spontaneous immunologic changes. Its pathogenesis is poorly understood, although histopathologic features have suggested immune complex (IC)-mediated injury. Abundant circulating antibody is present but no convincing correlation has been established between circulating IC and ENL. We have examined cutaneous leprosy lesions in vivo using blisters induced by prolonged gentle suction to determine whether or not IC are demonstrable in lesions with or without ENL, using an IC assay based on monoclonal rheumatoid factor binding. We also examined whether antibodies involved in such IC are produced locally or reach the skin via the circulation. Surprisingly large quantities of IC were found in ENL lesions, and in some cases the quantities were significantly higher than in matching serum. Total IgG, IgA, and IgM in the skin were not higher than expected, however. Attempts to demonstrate increases in intracutaneous levels of specific anti-Mycobacterium leprae antibodies were unsuccessful. This is the first report of the demonstration of IC in suction blister fluid. The results indicate that large quantities of IC may be present in cutaneous leprosy lesions and are consistent with the hypothesis that they are formed in situ when circulating antibody combines with antigen in the skin. The nature of the antigen in these IC remains undefined. PMID- 1623644 TI - A controlled study of lymphocyte subsets in rheumatoid arthritis. AB - The purpose of this study was to determine if patients with rheumatoid arthritis (RA) exhibited unique patterns of peripheral blood lymphocyte (PBL) subsets in comparison to patients with osteoarthritis (OA) and, further, if such differences related to disease activity or nondisease factors. Data from 63 RA patients and 47 OA patients revealed that the RA patients had lower absolute numbers of CD2+ and CD4+ lymphocytes. Small differences also were found in selected B-cell subsets and subsets of lymphocytes expressing CD16 and/or CD57 antigens. Further analysis revealed that these differences were due primarily to the effects of cytotoxic medications in the RA group. However, there were also alterations in some subsets independent of medication groups. PBL subsets in RA patients did not relate to chronic low-dose prednisone or measures of disease activity. This study demonstrated the need to control carefully for variables such as age and medication in immunophenotypic investigations of RA. PMID- 1623645 TI - Nucleosomes and DNA bind to specific cell-surface molecules on murine cells and induce cytokine production. AB - The molecular basis for the cellular interaction of DNA and nucleosomes and the physiological consequences of this binding were examined. Both DNA and nucleosomes were demonstrated to bind specifically to the surface of human peripheral blood mononuclear cells and the murine T cell line S49. Western blots of S49 cell membranes, using probes of biotin-labeled DNA and nucleosomes, showed reactivity at 29 and 69 kDa. Functionally, the interaction of DNA and nucleosomes with murine spleen cells stimulated the release of significant amounts of IL-6 activity. There is evidence that nucleosomes, a product of apoptosis, are the major component of circulating DNA found in the plasma of patients with systemic lupus erythematosus (SLE). The interaction of nucleosomes with cell-surface DNA binding molecules may have physiological relevance to some of the immune aberrations observed in patients with SLE. PMID- 1623646 TI - Antibodies to endothelial cells in primary vasculitides mediate in vitro endothelial cytotoxicity in the presence of normal peripheral blood mononuclear cells. AB - Twenty-eight out of 62 patients with Wegener's granulomatosis and micropolyarteritis display circulating antiendothelial cell antibodies (AECA) detectable by a cell surface radioimmunoassay. These antibodies do not induce an in vitro endothelial damage either alone or in the presence of fresh complement; however, 50% of IgG-AECA positive sera can be cytotoxic in the presence of human normal peripheral blood mononuclear cells (PBM) at high effector/target ratios. The specificity of the PBM-mediated cytotoxicity is supported by the absence of the phenomenon in AECA negative sera, by the disappearance of the lytic effect after absorption of AECA, and by the finding that cellular-mediated cytotoxicity can be reproduced by purified IgG-AECA positive fractions. On the contrary, polymorphonuclear leukocytes or adherent mononuclear cells are not involved in such a cytotoxic activity. AECA seem to be directed against determinants consitutively expressed on the endothelial surface since the activation of endothelial cells by interleukin-1 beta or interferon-gamma affects neither the antibody binding nor their ability to mediate 51Cr release in the presence of PBM. These findings favor the hypothesis for a possible direct pathogenetic role of circulating AECA in the in vivo vascular damage. PMID- 1623647 TI - Peripheral B cells with intracytoplasmic mu chains in HIV infection. AB - Besides the major alteration of T lymphocytes, B-cell anomalies have been reported in HIV infection, related to late stages of B-cell maturation, and considered to result from the dysregulation of T/B interactions. Because T cells are also involved in the control of lymphopoiesis and/or because of specific alterations of the B lineage, anomalies of B-cell maturation could occur in HIV infected patients. We investigated the presence of immature pre-B lymphocytes, characterized by cytoplasmic mu chains, in 35 peripheral blood samples from healthy controls, 82 from HIV-positive/non-AIDS patients, and 45 from AIDS patients. Significant numbers of such cells were observed in 48% of HIV seropositive patients and in 40% of the patients with AIDS disease. The presence of pre-B cells correlated with higher numbers of CD8+ and/or CD57+ cells and of peripheral lymphocytes. These data suggest that B-cell dysregulation in HIV infection may lead to the abnormal release of immature B cells in the peripheral blood. This observation may be interpreted as a sign of bone marrow activity. PMID- 1623648 TI - Tumor necrosis factor-alpha inhibitory activity in urine of Kawasaki disease. AB - Recently it has been reported that naturally occurring inhibitors of tumor necrosis factor alpha (TNF-alpha) were demonstrated in urine of some acute febrile patients. We investigated whether TNF-alpha inhibitory activity in urine increases during acute Kawasaki disease (KD). TNF-alpha inhibitory activities in urine were measured by a cytotoxicity assay on the TNF-susceptible cell line L929. KD patients had increased TNF-alpha inhibitory activities in urine during the acute stage and returned to a normal range during the convalescent stage. Our results suggest that the TNF-alpha inhibitor in urine is part of the regulatory system of TNF-alpha, which might be responsible for vascular injury during acute KD. PMID- 1623649 TI - Frequency of selective IgG subclass deficiency: a reappraisal. PMID- 1623650 TI - Heparin and myocardial infarction. PMID- 1623651 TI - PTCA in patients with stable angina pectoris and multivessel disease: is incomplete revascularization acceptable? AB - Of all coronary angioplasties performed nowadays, 40% of the patients have multivessel disease. Angioplasty in patients with multivessel disease can be performed with a high immediate clinical success rate and an acceptable major complication rate. However, complete anatomic revascularization with coronary angioplasty is achieved in only 32 to 59%. This raises concern about the immediate and long-term outcome of patients in whom incomplete revascularization is achieved. This report reviews the literature and provides evidence that incomplete revascularization with coronary angioplasty is a safe and effective treatment in selected patients with multivessel disease, provided that adequate (functional) revascularization can be achieved. Adequate revascularization includes dilation of all significant lesions supplying large areas of viable myocardium. PMID- 1623652 TI - The effect of treatment on survival in congestive heart failure. AB - Congestive heart failure (CHF) is a disorder characterized by a variety of clinical, biochemical, electrophysiological, and hemodynamic abnormalities. During the past two decades, numerous drugs have been employed in the treatment of this complex syndrome, and many agents have been shown to improve symptoms and ventricular function in patients with CHF. Because CHF is associated with a high risk of death, treatment should be directed not only toward the relief of symptoms, but also toward a reduction in mortality. Many variables have been shown to be related to survival; taken individually, however, each is limited in its utility in predicting prognosis. In recent years, large-scale studies with large sample sizes have directly assessed the effects of treatment on mortality in CHF. Results from these trials indicate that vasodilators and angiotensin converting enzyme (ACE) inhibitors may improve mortality in patients with symptoms of heart failure. Additional trials are now in progress to evaluate the effect of treatment on patients with asymptomatic left ventricular dysfunction. PMID- 1623654 TI - Multifocal atrial arrhythmia--a frequent misdiagnosis? A correlative study using the computerized ECG. AB - All computerized ECGs taken over a 17-week study period were reviewed for the detection of multifocal atrial arrhythmia (MAA)--tachycardia or rhythm--and correlated with the diagnostic statement of the ECG computer system. MAA was identified by the authors in 96 of 11,610 (0.8%) computerized ECGs. In all instances, this specific arrhythmia was misclassified by the computer system as atrial fibrillation. Moreover, during the over-read, only 27.1% of ECGs were correctly diagnosed by the assigned electrocardiographers blinded to this study. MAA is not an uncommon atrial arrhythmia since it was identified in 14% of computerized ECGs interpreted as atrial fibrillation. This study supports the inference that MAA is indeed frequently misdiagnosed by most physicians and the need for improved ECG computer analysis programs for reliable detection of MAA. PMID- 1623653 TI - The effects of captopril on training in patients with ischemic heart disease. AB - We studied a group of 30 patients to determine the effect of captopril on the exercise training response after a period of training in patients with ischemic heart disease but without cardiac failure. The study was a double-blind placebo controlled comparison of captopril and placebo. The patients studied were 28 men and 2 women, mean age 53.6 +/- 6.9 years. All were 8 to 12 weeks postmyocardial infarction or coronary artery bypass surgery. These patients underwent an organized exercise training program consisting of exercise training sessions 3 times weekly for a period of 8 weeks. On commencement and completion of the program patients were assessed for exercise tolerance using submaximal exercise stress testing. Patients were assessed in the untreated state. Both groups showed a statistically significant training effect with increased exercise duration, decreased heart rate for equal workload, increased energy expenditure, and reduced functional aerobic impairment. There was no statistically significant change in systolic blood pressure, but the captopril group alone showed a significant reduction in diastolic blood pressure (p less than 0.001). The change in heart rate at rest over the 8-week period was not significant in both groups. In summary, this study shows that treatment with captopril does not affect the exercise training response in patients with ischemic heart disease undergoing an organized exercise training program. PMID- 1623655 TI - Clinical significance of serum colloid osmotic pressure in relation to pulmonary edema and coronary instability in patients with unstable angina. AB - Several investigators demonstrated that severe reduction of colloid osmotic pressure (COP) predicts a fatal outcome in patients with cardiopulmonary failure. To evaluate the clinical significance of COP in relation to pulmonary edema, we studied 117 patients with unstable angina admitted in the hospital within 24 h after the chest pain. The mean COP of all 117 patients was 24.8 +/- 3.7 mmHg. COP was significantly lower in patients with pulmonary edema, according to the chest x-ray findings, compared with the patients without it. Among 26 patients with emergency coronary arteriography, a fairly good correlation was observed between coronary jeopardy score and COP (r = -0.57, p less than 0.005). Furthermore, COP in patients who survived 26 months after the hospital discharge was significantly higher than that of the nonsurvivors. Thus, measurement of COP is advised for monitoring patients with unstable angina. PMID- 1623656 TI - Blood coagulability and fibrinolytic activity before and after physical training during the recovery phase of acute myocardial infarction. AB - The effects of physical training on hemostatic parameters were evaluated in 56 postmyocardial infarction (MI) patients before and after one month of systematic physical training and in 30 control post-MI patients, who did not undergo such training. There were no significant changes in prothrombin time (PT) and alpha 1 antitrypsin (alpha 1AT) at the beginning and end of the study in either group. Levels of fibrinogen, Factor VIII: C (VIII:C) and von Wildebrand antigen (vWf:Ag), and activities of ATIII and plasminogen (Plg) were significantly decreased in the group with physical training (p less than 0.05), while values were unchanged in the control group. Hematocrit, platelet counts, and alpha 2 plasmin inhibitor (alpha 2PI) activities also decreased in the physical training group (p less than 0.05). In contrast, these variables increased in the control group (p less than 0.05). Activated partial thromboplastin time (aPTT) tended to be prolonged in the group with physical training, while it was shortened in the control group. In a subset of 20 patients with physical training, resting levels of plasmin-alpha 2PI complex (PIC), thrombin-antithrombin III complex (TAT), protein-C (P-C:Ag), plasminogen activator inhibitor-1 (PAI-1), VII:C, and P-C activities had significantly decreased after one month of physical training (p less than 0.05), although tissue plasminogen activator activities remained unchanged. Physical training appeared to suppress coagulability as indicated by the decrease in fibrinogen, VIII:C, vWf:Ag, VII:C, and TAT, and prolongation of aPTT. The decrease in plasminogen, t-PA:Ag, alpha 2PI, PAI-1, and PIC after physical training may result from the decreased coagulability. In conclusion, physical training appears to induce a suppression of the coagulation system in patients in the recovery phase of MI. PMID- 1623657 TI - 24-hour efficacy of once-daily diltiazem in essential hypertension. AB - The safety and effectiveness of a once daily formulation of diltiazem hydrochloride (diltiazem CD) in the treatment of essential hypertension was assessed in a total of 127 patients with supine diastolic blood pressures (DBP) of 95 to 110 mmHg randomized to diltiazem CD (n = 61) or placebo (n = 66). Patients were titrated to doses of 120, 240, or 360 mg to achieve DBP reduction to less than 90 mmHg. At end study diltiazem CD changed trough supine SBP and DBP by -8.4 +/- 1.7 (p = 0.0009) and -8.6 +/- 1.1 mmHg (p = 0.0075), respectively. Heart rate was not significantly changed (-1.3 +/- 1.1 beats/min, p = 0.4362). The average dose of diltiazem CD was 268 mg with 69% achieving a clinical response. A subset of 47 patients underwent ambulatory blood pressure monitoring to assess the consistency of the effect over the full 24-h dosing interval. Diltiazem CD lowered DBP and SBP throughout the dosing interval. The overall side effect profile was similar to placebo. This study provides evidence of 24-h efficacy of this new, once daily formulation of diltiazem. PMID- 1623658 TI - A critical appraisal of indications for the implantable cardioverter defibrillator (ICD). AB - The implantable cardioverter defibrillator (ICD) is a remarkably effective therapy for reducing sudden cardiac death in patients with malignant ventricular arrhythmias. The indications for implantation of the ICD were approved in 1985 by the United States Food and Drug Administration; it could be implanted in patients who have experienced cardiac arrest or in those with recurrent ventricular arrhythmias which are not suppressed by anti-arrhythmic drugs in the electrophysiology laboratory. These established indications have not changed in the last seven years. In the near future, the release of third-generation ICDs (with antitachycardia pacing) will likely further expand indications for the device. Many patients with stable ventricular tachycardia who have not had syncope or cardiac arrest will receive a third-generation defibrillator. Also, three clinical trials now in progress--CABG-PATCH, Multicenter Automatic Defibrillator Implantation Trial (MADIT) and Multicenter Unsustained Tachycardia Trial (MUSTT)--are studying "pre-event" patients with low ejection fraction and electrical instability; some of the patients in each trial are being prospectively randomized to the ICD. Within the next five years we will have a better understanding of the role of ICD therapy in such patients. Until these studies are completed, it is important that the indications for the ICD not be expanded. PMID- 1623659 TI - Acute circumferential subendocardial infarction. AB - A 48-year-old black man had his first attack of chest pain on exertion, radiating to both arms, in December 1982 (angina pectoris). It was undoubtedly preceded by a period of asymptomatic coronary atherosclerosis of unknown duration. The first anginal attack was followed by three to four similar episodes over the next four months. The attacks became more prolonged, frequent, and severe thereafter (so called "pre-infarct" angina), and six days later the patient showed signs of having developed actual myocardial necrosis. The patient underwent saphenous vein coronary artery bypass surgery but could not be weaned from the pump. He died late on the day of surgery. He was found at autopsy to have severe old three vessel coronary artery disease with the myocardial changes that would be expected from the severe global ischemia to which this heart was undoubtedly subjected. Several basic and important differences between this sort of a circumferential subendocardial infarct and a transmural infarct are discussed, as is the basis for the striking subendocardial hemorrhage. PMID- 1623660 TI - Black scorpion envenomation: two cases and review of the literature. AB - Scorpion envenomation is quite common in India, southeast Asia, the U.S. southwest, and Israel (in the Negev and around Jerusalem). Yellow scorpion is considered the most dangerous scorpion that causes cardiac toxicity. Two patients are described, who lived in a nonendemic area of yellow scorpions and were envenomated by the black scorpion. Both suffered temporary cardiac involvement (manifested by electrocardiographic changes) which reverted to a normal pattern within 24 h. These are the first two cases that have been reported (from black scorpion envenomation) and indicate that the toxin of the black scorpion is also cardiotoxic, but much less than the "yellow scorpion" toxin. PMID- 1623661 TI - The transesophageal echocardiographic diagnosis of left atrial myxoma simulating a left atrial thrombus in the setting of mitral stenosis. AB - We report a case of left atrial myxoma simulating a thrombus on transthoracic echocardiography, but correctly diagnosed using transesophageal echocardiography. As this tumor is usually fatal unless surgically resected, a correct diagnosis is essential. Myxomas which do not prolapse between the mitral valve leaflets and coexist with mitral stenosis may be difficult to diagnose accurately using transthoracic echocardiography. The advantages of transesophageal compared with transthoracic echocardiography in the diagnosis of nonclassical left atrial myxoma are discussed. PMID- 1623662 TI - Intermittent coronary spasm during graded exercise. AB - We report a patient with Prinzmetal's angina with nearly normal coronary angiogram who not only developed severe myocardial ischemia during exercise, documented both electrocardiographically (ST elevation) and scintigraphically (with thallium-201), but also did so intermittently as the graded exercise progressed. Diagnostic coronary angiography showed spontaneous focal spasm of the proximal left anterior descending coronary artery. This unique response to exercise in a patient with variant angina suggests that factors other than catecholamine stimulation alone are active and rapidly attenuated in some patients. This phenomenon could be overlooked without appropriate electrocardiographic monitoring. PMID- 1623663 TI - Spontaneous and induced vasodepressor/vasovagal syncope in hypertrophic cardiomyopathy. AB - We describe a 47-year-old man affected with hypertrophic cardiomyopathy and frequent episodes of syncope. During ambulatory Holter monitoring and head-up tilt test, a syncopal attack was associated with sinus arrest and hypotension. This case suggests an additional mechanism of syncope in hypertrophic cardiomyopathy. PMID- 1623664 TI - William C. Roberts. PMID- 1623665 TI - Epidemiology of hypertrophic osteoarthropathy. PMID- 1623666 TI - Hypertrophic osteoarthropathy in the paediatric age. AB - Hypertrophic osteoarthropathy should be considered in any child who presents with a non-inflammatory synovitis of the knees, ankles and wrists and particularly if there is finger clubbing or soft tissue hypertrophy of the fingers. It is rare to get the typical facial appearances until after adolescence. Alteration in epiphyseal growth is associated with the periosteal reaction, as is change in the shape of the patella; whether this leads to premature osteoarthrosis is not yet certain. Secondary disease is common in cyanotic congenital heart disease, but its frequency appears to be decreasing with early treatment of such children. Chest infections are also better controlled so again it is less common, but does still occur, particularly in cystic fibrosis in the older age group who have intractable chest infections. It is seen but rarely in disorders such as inflammatory bowel disease or pulmonary metastases, particularly from bone tumours. PMID- 1623667 TI - Cardiogenic hypertrophic osteoarthropathy. AB - It has been a generally held notion that the association of cyanotic congenital heart diseases with hypertrophic osteoarthropathy (HOA) is exceptional. However, recent prospective studies have demonstrated the opposite to be true. More than a third of patients with cyanotic heart diseases have HOA. The skeletal changes are more prevalent, more persistent and more severe than in any other internal illness. The clinical features of cardiogenic HOA are here discussed. PMID- 1623668 TI - Lung diseases associated with digital clubbing. AB - Clubbing is classified into conditions in which it is commonly, occasionally, rarely and never observed. Hypertrophic osteoarthropathy may be a more extreme form of clubbing, but is more likely to be a related but nevertheless qualitatively different phenomenon. Megakaryocytes or platelet clumps impacting in a digital stratum are plausible causes of clubbing, through the local release of platelet-derived growth factor (PDGF). PMID- 1623669 TI - Diagnostic imaging in hypertrophic osteoarthropathy. AB - This review discusses our experience with conventional radiography and advanced imaging techniques in the evaluation of diverse soft tissue, skeletal and joint abnormalities frequently observed in patients with both the primary and secondary forms of hypertrophic osteoarthropathy. The manifestations include finger clubbing, elephant feet, cutis verticis gyrata, synovial effusion, periostosis, tuftal hypertrophy and acro-osteolysis. Its coexistence with other skeletal and joint diseases and its imaging differential diagnosis are also reviewed. PMID- 1623670 TI - History of hypertrophic osteoarthropathy (HOA). AB - Hypertrophic osteoarthropathy (HOA) was first described in 1868 as "hyperostosis of the entire skeleton". It has also been mistaken for acromegaly. In 1887-1888 the first description was given of a dermatological disorder "cutis verticis girata" which coexisted with the peculiar bone anomalies of HOA. In 1890 HOA was named "osteoarthropatie hypertrophiante pneumique". Later a distinction was made between the rare idiopathic (or primary) form, also called "pachydermoperiostosis" and the more common secondary form due to concomitant disorders involving the lungs and pleura. The primary form usually develops shortly after puberty or during adolescence and has not been found associated with underlying disease. Secondary HOA was initially called "hypertrophic pulmonary osteoarthropathy" because it is frequently associated with various malignancies or chronic infections of the lung and pleura. Later, since the site of primary disease may be elsewhere, involving the gut and the cardiovascular, hepatobiliary and endocrine systems, this designation fell into disuse. In some cases of secondary HOA, the osteoarthropatic and facial skin changes subside after pneumonectomy or other procedures. A disease resembling human HOA has been also described in dogs. PMID- 1623671 TI - Hypertrophic osteoarthropathy: rheumatologic manifestations. AB - Arthropathy can occasionally be an early clue to the diagnosis of hypertrophic osteoarthropathy (HOA). Joint effusions are typically relatively non inflammatory, while synovial membrane biopsies show a variety of vascular changes that suggest the consideration of several factors possibly involved in the pathogenesis of HOA. PMID- 1623672 TI - An historical approach to pachydermoperiostosis. PMID- 1623673 TI - The spectrum of dermatological symptoms of pachydermoperiostosis (primary hypertrophic osteoarthropathy): a genetic, cytogenetic and ultrastructural study. AB - Pachydermoperiostosis (PDP) is characterized by finger clubbing, periostosis and peculiar skin involvement (pachydermia, seborrhea and folliculitis). The aim of our work was to determine the occurrence of dermatological symptoms in patients with PDP and their relatives, and to study ultrastructural skin changes in the complete and incomplete forms of the disease. A genetic and cytogenetic study was performed in order to identify the mechanism of transmission, to discover possible links to other genetic and non-genetic diseases and to determine the chromosomal complement and eventual chromosomal anomalies. Pachydermia was the most frequent skin alteration together with seborrhea; folliculitis was present in five patients. In the relatives mild pachydermia was detected in 2 out of 26, while seborrhea was present in 6 subjects. Light microscopic observation showed acanthotic epidermis and endothelial hyperplasia in the dermis with partial occlusion of the lumen, lymphohistiocytic infiltrate, and thickening and packing of collagen fibers. Electron microscopy showed fibroblast activation with increased fibrillogenic activity as shown by hypertrophic Golgi complexes and rough endoplasmatic reticulum with cisternae filled with microfibrils. Endothelial cells partially or completely occluded the capillary lumen and presented an increased amount of Weibel Palade bodies. These data show that skin involvement in PDP is a prominent feature, that sometimes these symptoms may also be present in their relatives, and that endothelial and fibroblast activation is present in the skin. Unfortunately the cytogenetic study did not provide any information about possible karyotype abnormalities. PMID- 1623674 TI - Pathogenesis of hypertrophic osteoarthropathy. AB - The systematic study of patients with cyanotic heart diseases has led to a better understanding of the pathogenesis of hypertrophic osteoarthropathy (HOA). Current evidence suggests that in cases of right-to-left shunts of blood, HOA develops as a result of faulty pulmonary clearance of macrothrombocytes. There are theoretical grounds to suggest that a platelet-derived growth factor is also responsible for the acropachy associated with other types of internal illnesses. PMID- 1623675 TI - The role of vascular endothelium in fibroblast activation and tissue fibrosis, particularly in scleroderma (systemic sclerosis) and pachydermoperiostosis (primary hypertrophic osteoarthropathy). AB - The vascular endothelium is an organ that is distinguished by its versatility and ability to modulate its surroundings. Endothelial cells (EC) interact with a variety of cell types including fibroblasts (FB), smooth muscle cells, circulating mononuclear cells, platelets and other cell types. This paper will focus on the interaction between endothelial cells and fibroblasts in the process of fibrosis. Vascular changes are described in most human fibrotic models, i.e. radiation, bleomycin, wound healing and particularly in scleroderma. FB migration to the perivascular spaces and proliferation is seen in the early settings of tissue fibrosis. The role of EC in this process is not precisely known; however, the EC contribution to fibrosis is likely to be multifactorial and may involve a spectrum of delicate mechanisms and an array of chemical signals. The induction of FB chemotaxis and FB proliferation by the EC's release of chemotactic factors and mitogens is one possible pathway of FB activation. Another major mechanism involves EC mobilization, guidance and regulation of mononuclear cell infiltration in the perivascular spaces and the subsequent impact of that process on FB activation. Histologic studies of human fibrotic disorders have emphasized early FB proliferation. The role of EC in the induction of FB proliferation should be evaluated carefully in order to understand human fibrosis. PMID- 1623676 TI - Pachydermoperiostosis (primary hypertrophic osteoarthropathy): in vitro evidence for abnormal fibroblast proliferation. AB - Pachydermoperiostosis (PDP) is a disease characterized by the presence of pachydermia, periostosis and finger clubbing. Evidence that the skin and soft tissues are involved in the disease prompted the in vitro investigation of the behaviour of fibroblasts obtained from cutaneous biopsies of involved and apparently uninvolved PDP skin. PDP fibroblasts from affected skin demonstrated an abnormal proliferation, very rapid and tumultuous when compared to the growth of fibroblasts derived from apparently uninvolved skin and fibroblasts from the skin of healthy subjects. This characteristic was confirmed by the rate of thymidine incorporation, which was increased in PDP-affected fibroblasts (1152 dpm) compared to apparently non-PDP involved fibroblasts (273 dpm) and controls (262 dpm). Ultracentrifuged and non-centrifuged conditioned medium (CM) of fibroblasts affected or apparently not affected with PDP were used to evaluate the effect on the proliferation of healthy skin fibroblasts, compared to the effect of CM derived from healthy fibroblasts and from healthy fibroblasts incubated with 10% and 1% foetal calf serum. The CM of non-centrifuged PDP fibroblasts resulted in a statistically significant stimulation of fibroblast growth when compared to that expressed by ultracentrifuged PDP CM, healthy fibroblast CM and 10% stimulated CM. These data show that PDP fibroblasts maintain in vitro the capacity to proliferate at a higher rate than healthy fibroblasts and that in the CM residual cells and/or their debris may be present, inducing the abnormal growth of healthy fibroblasts. This evidence suggests that fibroblasts in PDP may play a role in the development of the disease. PMID- 1623677 TI - The "endothelium/platelet unit" in hypertrophic osteoarthropathy. AB - Various pathogenetic theories of hypertrophic osteoarthropathy (HOA) have been proposed (neurogenic, hormonal, artero-venous shunts, genetic theory), but none of them is able to satisfactorily explain the genesis of HOA. The hypothesis of a central role of the "endothelium/platelet unit" was recently discussed. Above all, the release of the platelet derived growth-factor (PDGF) contained in platelet granules is particularly interesting. In order to assess the microvascular involvement in HOA we set up a research project whose aims were to evaluate the morphology of the capillary network at the nailfold, the dynamic aspects of microcirculation and in vivo platelet function. Since this study is still in progress, for the time being we present only a few preliminary results. PMID- 1623678 TI - The medical and surgical treatment of finger clubbing and hypertrophic osteoarthropathy. A blind study with colchicine and a surgical approach to finger clubbing reduction. AB - In fourteen patients affected with pachydermoperiostosis (PDP), or primary hypertrophic osteoarthropathy, the efficacy of colchicine (0.5 mg day for one month) versus placebo on the main clinical features of the disease (finger clubbing, arthritis and pachydermia) was evaluated. In addition, in one patient the usefulness of surgical reduction of clubbed fingertips was investigated. Colchicine did not demonstrate any appreciable effect on finger clubbing (expressed in degrees) or pachydermia, while an effect on arthralgia (as evaluated by the Ritchie Index and Pain Scale) was observed. The surgical treatment of clubbed fingertips failed to show a satisfactory and stable reduction of the fingertips; two months after surgery the nail matrix apparently produced new tissue, once again enlarging and deforming the finger. These results suggest that low dose colchicine cannot be considered the drug of first choice for the treatment of PDP, while higher dosages, although effective, are not tolerated because of the severe side effects. An effective medical and surgical treatment for PDP will be found only when the pathogenetic mechanisms of the disease are clarified. PMID- 1623679 TI - The contribution of French researchers to hypertrophic osteoarthropathy. PMID- 1623680 TI - French practitioners in mid 18th century London. PMID- 1623681 TI - Dentistry for the nation. PMID- 1623683 TI - Shortcuts in drug evaluation. PMID- 1623684 TI - Clinical use of the Medication Event Monitoring System: a new window into pediatric compliance. PMID- 1623685 TI - Statistics and clinical trials. PMID- 1623686 TI - Drug clearance in patients with cystic fibrosis. PMID- 1623687 TI - Theophylline metabolism affected by mexiletine. PMID- 1623688 TI - HMG-CoA reductase inhibitors and sleep. PMID- 1623689 TI - Adaptive control with feedback strategies for suramin dosing. AB - Suramin, a drug used in the treatment of parasitic diseases, is currently being evaluated in clinical trials as an antineoplastic agent. The use of therapeutic drug monitoring and adaptive control with feedback in clinical trials of suramin was initially motivated by an association between acute neurologic toxicity and plasma suramin concentrations in excess of 350 micrograms/ml. We have prospectively examined the performance of both two- and three-compartment population pharmacokinetic models in controlling plasma suramin concentrations and have found that a three-compartment model best describes this drug. No correlation was found between the clearance of suramin and creatinine clearance, as had been previously hypothesized. The low systemic clearance of suramin and the number of parameters required to describe the three-compartment model suggest the need for a bayesian approach to the estimation of individual pharmacokinetics. PMID- 1623690 TI - Single-dose pharmacokinetics of cefpirome in patients with renal impairment. AB - The pharmacokinetic parameters of cefpirome (HR 810) were examined in 22 patients with different degrees of renal impairment. HPLC was used to analyze samples of blood and urine for cefpirome; and enzymatic assay of creatinine in serum and urine was used to assess kidney function. Creatinine clearance correlated linearly with both total and renal clearance of cefpirome. The loss of kidney function resulted in a decreased renal clearance, whereas the volume of distribution remained the same. This result led to an increase in the terminal half-life of the drug, from 2 hours in healthy subjects to 14 1/2 hours in patients with uremia. This increase also resulted in a prolonged high serum concentration well above the minimum inhibitory concentration. The following dosages are thus recommended: (1) creatinine clearance greater than 50 ml/min: normal daily dose, (2) creatinine clearance from 20 to 50 ml/min: 50% of normal daily dose, and (3) creatinine clearance less than 20 ml/min: 25% of normal daily dose. An initial loading dose of 1 gm, independent of renal function, is advised. Cefpirome was safe and well tolerated. PMID- 1623691 TI - Failure of controlled clinical trial data to reach the literature. PMID- 1623692 TI - Verapamil inhibits ethanol elimination and prolongs the perception of intoxication. AB - Ten young healthy men received verapamil (80 mg every 8 hours for 6 days) or placebo in a blinded, randomized, crossover design. On the sixth day, ethanol was administered as a single oral dose (0.8 gm/kg), and blood samples were collected over the following 12 hours for determination of verapamil, norverapamil, and ethanol concentrations. Compared with placebo, verapamil increased the peak blood ethanol concentration (106.45 +/- 21.40 to 124.24 +/- 24.74 mg/dl, p less than 0.05) and area under the ethanol concentration versus time curve (365.67 +/- 93.52 to 475.07 +/- 97.24 mg.hr/dl, p less than 0.005). Verapamil areas under the concentration versus time curves (AUC) were positively correlated (r = 0.71, p less than 0.05) to increased ethanol blood AUC values. Each subject's perception of ethanol intoxication was measured by use of a simple visual analog scale. Compared with placebo, verapamil significantly increased area under the effect versus time curve (10.19 +/- 7.6 to 13.83 +/- 7.81 cm.hr, p less than 0.002) but did not change the peak effect or time to peak effect. Ethanol effect versus concentration plots were not significantly different between verapamil and placebo treatment phases when increased ethanol concentrations during verapamil therapy were taken into account. The findings of our study suggest that verapamil significantly inhibits ethanol elimination, resulting in elevated blood ethanol concentrations that prolong the intoxicating effects of alcohol. PMID- 1623693 TI - Effect of carbetocin, a long-acting oxytocin analog on the postpartum uterus. AB - Carbetocin, a long-acting oxytocin analog, was administered by intravenous and intramuscular injection to 40 women 24 to 48 hours postpartum. Intravenous injection of 8 to 30 micrograms produced a tetanic uterine contraction within 2 minutes, lasting about 6 minutes, followed by rhythmic contractions for a further 60 +/- 18 minutes. Intramuscular injection of 10 to 70 micrograms also produced tetanic contraction in less than 2 minutes, lasting about 11 minutes, and followed by rhythmic contractions for an additional 119 +/- 69 minutes. The prolonged duration of activity after intramuscular compared with the intravenous carbetocin was significant (p = 0.020). Carbetocin produced mild lower abdominal cramping in most patients and severe pain in three patients who received 50 or 100 micrograms intravenously or 70 micrograms intramuscularly. Approximately half of the patients also experienced flushing and warmth. Although carbetocin has not yet been studied immediately postpartum, its prolonged uterine activity suggests that carbetocin may offer advantages over oxytocin in management of the third stage of labor. PMID- 1623694 TI - Differential effects of two dihydropyridine calcium antagonists in humans. AB - We studied the effects after single doses of niguldipine (0.3, 0.6, and 0.9 mg intravenously; 8 and 16 mg orally) and nifedipine (2 mg intravenously; 20 mg orally) in healthy male volunteers in randomized placebo-controlled experiments. Total peripheral resistance (TPR), heart rate-corrected electromechanical systole (QS2c), and preejection period (PEPc) were assessed noninvasively. Both drugs induced a similar pronounced decreased in TRP, indicating peripheral vasodilation, followed by increasing heart rate and cardiac output, a decrease in diastolic blood pressure, and a shortening of the PEPc. QS2c was unchanged after niguldipine. The prolongation of QS2c after oral nifedipine is suggestive of a negative inotropic effect. We conclude that the vasodilatory effects of dihydropyridines may (as for nifedipine) or may not (as for niguldipine) be associated with changes that are suggestive of negative inotropic effects, and that this difference is detectable by noninvasive methods in healthy subjects. PMID- 1623695 TI - Treatment of opioid-induced constipation with oral naloxone: a pilot study. AB - Opioids cause constipation by binding to specific opioid receptors in the enteric and central nervous systems. First-pass glucuronidation limits systemic bioavailability of oral naloxone. This study was designed to determine if oral naloxone could reverse opioid-induced constipation without precipitating abstinence or recrudescence of pain in opioid-dependent individuals. Concentrations of unmetabolized and total naloxone, including naloxone glucuronide, were measured by radioimmunoassay. A dose-related increase in symptoms of laxation resulted in all three opioid-dependent patients studied that paralleled the increase in active and total naloxone plasma levels. Withdrawal symptoms occurred with plasma naloxone area under the plasma concentration-time curves above 550 ng.min/ml and with dosing intervals less than 3 hours. Peak plasma levels did not predict withdrawal. Oral naloxone ameliorates opioid induced constipation in opioid-dependent persons. Titration of dose to a maximum of 12 mg at least 6 hours apart may be needed to avoid adverse reactions. PMID- 1623696 TI - AIDS debate continues. PMID- 1623697 TI - OSHA workplace requirements in effect: direct impact on physician offices. PMID- 1623698 TI - Cumulative contents of volumes 1 to 40 and cumulative author index of volumes 1 40. PMID- 1623699 TI - Variation in restorative treatment decisions: application of Receiver Operating Characteristic curve (ROC) analysis. AB - It has been evident for many years that dentists, when planning treatment for patients, do not act in a standard manner, and previous research has shown there to be wide variations in treatment planning amongst groups of dentists. Signal detection theory and Receiver Operating Characteristic (ROC) analysis allows measurement of an observer's ability to detect a lesion, while at the same time allowing examination of how a lesion, once perceived, is judged to be in need of treatment. An ROC curve is constructed by plotting the sensitivity (or true positive rate) of decisions made, against the false positive rate (equivalent to 1-specificity) when various decision attitudes, from interventionist to non interventionist, are held. Fifteen pairs of simulated bitewing radiographs were shown to 20 dentists, who were asked to specify, for each approximal lesion, whether or not they would place a conventional restoration. The 7200 decisions made by the dentists were validated by sectioning and microscopically examining the teeth. The mean sensitivity of the dentists' decisions, when the strictest operating thresholds were held and caries into dentine was the validating criterion, was 0.26 and the mean specificity was 0.96. ROC analysis shows that when operating at the strictest threshold, the dentists were implying that specificity was weighted as being 2.7 times more important than sensitivity. ROC analysis leads to insight into how dentists differentially weight the true and false, positive and negative, outcomes of their decisions and thus allows explanation of why two dentists would rarely make exactly the same treatment plan for one patient, and also why different treatments might be offered to two patients exhibiting the same levels of disease. PMID- 1623700 TI - Caries development after termination of a fluoride rinsing program. AB - In a municipality near Copenhagen, Denmark, where fortnightly fluoride rinses with 0.2% neutral sodium fluoride had been performed for more than a decade, 1306 children from kindergarten through 6th grade were stratified by school and grade and randomly distributed into two groups. One group continued the fluoride rinses, the other group had the fluoride solution replaced with distilled water. Both solutions were slightly flavored. 1083 children completed the 3-yr trial. Caries was recorded clinically by the dentists in the municipal dental service using the diagnostic criteria for the Child Dental Health Services, and on bitewing radiographs by one of the authors applying the criteria developed by GRONDAHL et al. Permanent molars and premolars were included in the study. Clinically, caries increment in the two groups was the same with pits and fissures containing 94% of the DMFS. According to the radiographs, caries progression in the water group was higher than in the fluoride group. This difference was statistically significant for the surfaces erupting during the study (P less than 0.05). PMID- 1623701 TI - Extending recall intervals--effect on resource consumption and dental health. AB - The dental health of children has improved in recent years. This has stimulated more flexible planning and implementation of public dental care programs. The aim of the study was to compare time required for dental care and changes in dental health over a 2-yr period for patients examined and treated every 12 months and patients examined and treated every 24 months. The material comprised 185 children aged 3, 16 and 18 yr. Children with high caries prevalence were not included in the material. Time used for examination and treatment and dental health parameters were recorded. The data were analyzed using multiple linear regression analysis. Mean time used for examinations and mean total time used by the dental health service over the 2-yr period were significantly less for patients examined every 24 months than for patients examined every 12 months, while the treatment times did not differ between the groups. The longer recall interval was associated with greater DMFS increment but this was not statistically significant. The study indicates that the dental health service in Norway could save resources, i.e. increase the productivity in the short term by extending the intervals between examinations. PMID- 1623702 TI - Dental health behavior in fathers of young families in Finland. AB - The purpose of this study was to examine dental health behavior in young fathers by means of a questionnaire for subjective evaluation of dental status, frequency of caries and visits to the dentist. Cariogenic diet was estimated by the consumption of sweets, confectionary and soft drinks. The participation rate 18 months after the birth of the family's first child was 73.1%. The mean age of the respondents was 28.1 yr (range 17-49; SD 4.6). When background factors were considered, it was observed that cariogenic diet was more often mentioned by participants from the lower social groups. The standard of the wife's knowledge level was an important indicator of dental care behavior in the fathers. If the wife's knowledge level was high, the father assessed the future condition of his child's teeth as good. PMID- 1623703 TI - Validity of a patient self-completed health questionnaire in a primary care dental practice. AB - 1500 patient medical histories derived from self-completed health questionnaires alone and from a combination of questionnaire, structured interview by a dentist, and selective reference to family doctors were compared. In 4.25% of cases, the questionnaire medical history was significantly deficient. Such questionnaires yield an inadequate medical history when used on their own. PMID- 1623704 TI - Prevalence of caries in adolescents in relation to diet. AB - The aim of the present study was to compare dietary habits between adolescents with high or low dental caries prevalence. All 15-yr-old adolescents living in a small community in Northern Sweden were studied in 1987, 1988, and 1989. The median values for energy and nutrient intake exceeded or were close to the recommendations (SNR89) given by the Swedish National Food Administration. The fiber intake did not reach the recommended daily amount even for the 90th percentile of the studied cohort. Nineteen percent of the adolescents had caries free teeth and 10% had nine or more decayed or filled surfaces. There was no difference in daily sucrose intake or average number of meals per day between these two groups. The group with nine or more decayed or filled surfaces had worse dietary habits, expressed as a higher fat intake, lower intake of complex carbohydrates, and lower density of iron (mg/MJ) than the group with no dental caries. Dietary counseling by dentists should be a valuable addition to other caries prophylactic measures taken by the dentists. PMID- 1623705 TI - Effect of conventional dental restorative treatment on bacteria in saliva. AB - Dental caries results from the dissolution of mineralized dental tissues by the metabolic by-products of oral bacteria colonizing the surface of teeth. The principal modality for dealing with this infectious process is through restorative treatment which removes the pathologic tissue and replaces it with a variety of inert materials. The purpose of this study was to evaluate the effect of traditional restorative treatment on select oral bacterial populations. Fifty two females demonstrating high levels of mutans streptococci (greater than or equal to 2.5 x 10(4) colony forming units (cfu) per ml saliva) with no more than four missing posterior teeth were recruited for this study. Salivary levels of mutans streptococci, lactobacilli, total streptococci, and total cultivable bacteria were evaluated before, during, and after restorative treatment. Initial DMFS scores were established by two standardized examiners using bitewing radiographs and clinical examination, which was conducted under optimal conditions. All restorative treatment was completed by faculty members of the University of Alabama School of Dentistry using treatment plans developed by the DMFS examiners. The participants received a mean of 16.4 restored surfaces, which resulted in significant reductions of all the bacterial populations tested. All microbial populations monitored were predicted to return to their baseline levels within 151 days after restorative treatment in 50% of the participants. This study shows that conventional restorative treatment results in a significant reduction of bacterial populations including those associated with the dental caries process, i.e., mutans streptococci and lactobacilli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623706 TI - Investigation of delay in utilization of government dental services in Malaysia. AB - Although delays in seeking dental care among patients are frequently observed in daily practice, this problem has never been investigated in other utilization studies. This study attempts to establish the magnitude and severity of the problem of delay in a delivery system where cost is not a major barrier to utilization. 555 users of Government dental services were interviewed. Only 37% of them came promptly within 6 days of perceiving a dental need. The majority (63%) had delayed their dental visit for more than 1 week. In fact, the highest frequency of delay was for more than 1 month. Prompt attendance was found to be associated with people who regularly came for asymptomatic check-ups. In contrast, more than 50% of those who thought they needed fillings and extractions had delayed their visit for more than a month. The main causes of delays were attributed to work commitments and the lack of perceived need for urgent care. Barriers related to transport or financial problems were ranked very low. The implications of these findings are discussed. PMID- 1623707 TI - Evaluation of appropriate use of dietary fluoride supplements in the US. AB - Recent epidemiologic and related evidence suggests the following trends: 1. the prevalence of caries continues to decline in children of the US and several other developed countries; 2. the prevalence of mild dental fluorosis is increasing; 3. the majority of the cariostatic effects of fluoride are topical; and 4. dietary fluoride supplements are a risk factor for dental fluorosis. These trends, and the scientific evidence on fluoride and fluorosis, suggest that it is time to re evaluate the use of dietary fluoride supplements. This paper examines the evidence for each of the four trends and the use of fluoride supplements in caries prevention today. PMID- 1623708 TI - Prevalence of dental caries in school children of Lahore, Pakistan. PMID- 1623709 TI - Periodontal conditions of 6-15-yr-olds in various fluoride areas in Greece. PMID- 1623710 TI - Caries, gingivitis and oral hygiene in urban and rural pre-school children in Indonesia. PMID- 1623711 TI - Periodontal status of adults in central Saudi Arabia. PMID- 1623712 TI - Possible explanations for decline in tooth decay in New Zealand. PMID- 1623713 TI - Agreement between oral contraceptive users and prescribers: implications for case control studies. AB - Case-control studies examining the effects of oral contraceptives (OC) are prone to misclassification bias due to errors in assessment of OC use. Concern about inaccurate exposure histories has increased since current studies require women to recall OC use over prolonged periods of time. In preparation for a case control study of breast cancer and OC use, an investigation was carried out to assess agreement between women's lifetime histories of OC use (covering a period of up to 20 years) and prescribers' records. OC histories were obtained during personal interview with 218 women who had used OC at some point in their lives (127 breast cancer patients, 91 controls). Recall was aided by an album with color photographs of all OC marketed in the Netherlands from 1962 onwards (n = 65), and a calendar that covered the women's life span from date of birth to menopause. The participants were asked for the names of all physicians who prescribed OC for them. The rate of response from the prescribers was high (94%), but only half of the forms provided useful information. Patient-prescriber agreement on brand names (including dosage) was 70%. About half of the women agreed with their prescribers on starting dates to within less than a year's difference. Approximately the same percentage of agreement was found for stopping dates. Multiple linear regression indicated that agreement on brand names and dates of usage was lower for women of low socioeconomic status, for healthy women (as compared to breast cancer patients) and for periods of pill use that had to be recalled from the more distant past. Agreement on total duration of use was high enough to permit testing of a moderately strong duration-response relationship in a case-control study. PMID- 1623714 TI - Contraceptive use in Vietnam: the effect of individual and community characteristics. AB - Data from the 1988 Vietnamese Demographic and Health Survey and the 1990 Vietnam Study of Accessibility of Contraceptives were used in this analysis to determine how selective individual and community characteristics influenced the use of modern methods of contraception in Vietnam. Although there were no significant differences in the use of contraceptives between women with a primary education and those with a higher educational attainment, the illiterate women with no formal education were significantly less likely to use modern methods of contraception. Women living in provinces with high infant mortality rates were significantly less likely to use modern methods of contraception than women in low-infant-mortality provinces. Independent of other individual and community characteristics, there were no significant differences in the use of contraception between urban and rural women. PMID- 1623715 TI - Comparison of condom breakage during human use with performance in laboratory testing. AB - This paper combines results from a study of the determinants of condom quality and use conducted by The Population Council in two countries in the Caribbean with results from a condom breakage study conducted by Family Health International (FHI) in the United States. The studies, conducted two years apart, compared the breakage rates of condoms from the same lot during human use to their performance in laboratory test results. Breakage rates of 12.9% for Barbados, 10.1% for St. Lucia and 6.7% for the United States compared to passing ASTM laboratory tests suggest that existing laboratory tests as used with the current pass/fail standards are either not sufficiently sensitive or not well defined to reliably predict condom performance during human use. The study also suggests that user behaviors and practices may be a factor in condom breakage. If the condom is to be an effective method against unplanned pregnancy and STD/HIV infection, and if consumer confidence is to be retained, condom breakage during sexual intercourse must be reduced. PMID- 1623716 TI - Contraceptive efficacy of polyester-induced azoospermia in normal men. AB - The contraceptive effect of a polyester sling applied to the scrotum was studied in 14 men. The suspensor was worn for 12 months. Follow-up investigations comprised periodic check of semen character, testicular size, rectal-testicular temperature difference, serum reproductive hormones and testicular biopsy. The electrostatic potentials generated by friction between the polyester suspensor and the scrotal skin were determined. Female partners used contraceptives until the men became azoospermic. After 12 months, the suspensor was abandoned and the aforementioned investigations were performed again. In the suspensor-wearing period, all men became azoospermic after a mean of 139.6 +/- 20.8 sd days, with decrease in both testicular volume (P less than 0.05) and rectal-testicular temperature difference (P less than 0.001). Serum reproductive hormones showed no significant change (P greater than 0.05). Seminiferous tubules revealed degenerative changes. No pregnancy occurred during this period. The polyester suspensor generated electrostatic potentials (mean 366.4 +/- 30.5 sd volt/cm2 by day and 158.3 +/- 13.6 sd volt/cm2 by night). In the suspensor-release period, the sperm concentration returned to the pre-test level in a mean period of 156.6 +/- 14.8 sd days. Likewise, the testicular volume and rectal-testicular temperature difference were normalized. The 5 couples, who had planned to become pregnant, conceived. The azoospermic effect of the polyester sling seems to be due to two mechanisms: 1) the creation of an electrostatic field across the intrascrotal structures, and 2) disordered thermoregulation. To conclude, fertile men can be rendered azoospermic by wearing the polyester sling. It is a safe, reversible, acceptable and inexpensive method of contraception in men. PMID- 1623717 TI - Acceptability of Norplant-2 rods as a method of family planning. AB - The Norplant-2 rod system consists of two silastic rods in which levonogestrel has been incorporated with the polymer. The continuation rate at the end of five year was 62%. No accidental pregnancies occurred throughout the five years of use. The post-removal conception rate in women desiring pregnancy was 70.8% at the end of two years. The majority of acceptors were happy with the rods and 86.8% expressed the desire to have another set of implants inserted following removal of the first set. The study shows the Norplant-2 rod system to be a well accepted method of family planning. PMID- 1623718 TI - Effect of Norplant-2 rods on liver, lipid and carbohydrate metabolism. AB - The effect of Norplant-2 rods on liver, lipid and carbohydrate metabolism was evaluated in 100 women using Norplant-2 rods. Besides a significant increase in serum bilirubin, there was no other obvious evidence to suggest any possible hepatocellular dysfunction with the use of Norplant-2 rods. As regards lipid metabolism, decreases in total triglycerides, cholesterol and LDL-cholesterol and HDL-cholesterol were initially seen. These parameters returned to their preinsertion mean at the end of five years. As a result, the value of the HDL cholesterol/total cholesterol - HDL-cholesterol and LDL-cholesterol/HDL cholesterol ratios remained around their preinsertion value at the end of five years. All this appears to indicate that the use of Norplant-2 rods is not directly contributory to cardiovascular risk. The use of Norplant-2 rods was not associated with any significant effect on carbohydrate metabolism. PMID- 1623719 TI - Effects of STS-557 and 20 Aet-1 on sperm functions and serum level of testosterone in bonnet monkey (Macaca radiata). AB - Treatment of adult male bonnet monkeys with STS-557 (17 alpha-cyanomethyl 17 beta hydroxy estra-4, 9(10)-dien-3-one; 12 mg/monkey daily for 15 weeks; i.m.) reduced the sperm count from the 9th week, leading close to azoospermia on the 2nd post treatment week which persisted until the 10th post-treatment week and normalcy was restored on the 13th post-treatment week. The sperm motility was reduced from the 9th week of treatment to 8th post-treatment week. The fertilizing ability of spermatozoa (formation of swollen sperm head or pronuclei in zona-free hamster eggs) was abolished from the 8th week of treatment to the 7th post-treatment week. The serum level of testosterone was reduced from the 2nd to 12th week of treatment (data on subsequent weeks were not collected). When 20 Aet-1 (testosterone-trans-4-n butyl cyclohexyl carboxylate; 40 mg/monkey, single; i.m.) was administered on the first day of STS-557 treatment, the sperm count was reduced from the 10th week, with near azoospermia ensuing on the 13th week which continued until the 8th post-treatment week; recovery was observed on the 12th post-treatment week. The motility was low from the 8th week of treatment to 6th week after withdrawal of treatment. The fertilizing ability of spermatozoa was abolished from the 8th week to the 12th week of treatment (data on last week of treatment were not collected). The serum level of testosterone was maintained within normal range except on the 2nd, 6th and 12th week of treatment. 20 Aet-1 alone had no significant effect on these parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623720 TI - Histopathological and biochemical effects of gossypol acetate on pituitary gonadal axis of male albino rats. AB - Histopathological and biochemical effects of gossypol acetate (GA) on pituitary gonadal axis were investigated. 10 and 25 mg GA/kg were administered orally to sexually mature adult male Wistar rats for 4 and 5 weeks, respectively. STH and LTH/PRL cells showed no significant changes as compared to those of controls while TSH cells showed hypertrophy, hyperplasia and degranulation in both experimental groups. Pituitary FSH, LH/ICSH cells showed progressive regression. Gonosomatic indices of sex accessory glands at 25 mg showed significant reduction in the experimental animals as compared to those of controls. The diameter of seminiferous tubules reduced and azoospermia developed. Sertoli and Leydig cells also regressed. At 10 and 25 mg GA treatment, spermatogenesis ceased at secondary spermatocytes and spermatogonia stages, respectively. Epididymis and prostate regressed. Seminal vesicle showed no significant histological variations as compared to that of control except reduction in secretion. Biochemical observations revealed increased levels of acid phosphatase, fructose and citric acid and significant reduction in glycerylphosphoryl choline in reproductive glands of both experimental groups as compared to those of controls. Possible mechanism of antifertility action of GA is discussed. PMID- 1623722 TI - Introduction of ultrasound examination. PMID- 1623721 TI - The effects of a combined contraceptive vaginal ring releasing ethinyloestradiol and 3-ketodesogestrel on vaginal flora. AB - Fifty nine women with documented normal ovulatory cycles and with no symptoms of vaginal infection were divided into four groups. Each group used a combined contraceptive vaginal ring (CCVR) with a mean daily release rate of 0.015 mg of ethinyloestradiol (EE) and 0.120 mg of 3-ketodesogestrel (3-KDG) per day, for one cycle of either 21, 28, 42, or 56 days. Cultures from the posterior vaginal fornix and from the endocervical canal were obtained immediately before insertion of the ring and on removal of the ring. Changes in the numbers of vaginal cells, aerobic and anaerobic bacteria, Chlamydia trachomatis, Gardnerella vaginalis, yeasts and Trichomonas vaginalis were documented at the end of each treatment. Intra- and inter- group changes in the vaginal flora were assessed at the end of each treatment. The comparison between the number and type of flora showed no significant change between the pre-treatment population and the post-treatment population. The results of this study suggest that the use of this CCVR for 21, 28, 42 and 56 days is not associated with an increase in inflammatory cells or pathogenic bacteria. PMID- 1623723 TI - Leukocyte adhesion deficiency among Holstein cattle. PMID- 1623724 TI - Endocrine-immune interactions: potential role for somatotropic axis in modulating responses to endotoxemia in cattle. PMID- 1623725 TI - Thymoma in a domestic rabbit. AB - Thymic tumors are uncommon in small domestic animals, and thymomas are infrequently reported in rabbits. This report presents a 7-year-old Netherland dwarf rabbit with an anterior mediastinal mass which caused hyperpnea, open-mouth breathing, swelling of the head, and exophthalmos. The mass was composed predominantly of lymphocytes, but the presence of thymic epithelial cells established the histologic diagnosis of thymoma. PMID- 1623726 TI - Swine models for cardiovascular research: a low stress transport and restraint system for large swine. AB - A restraint and transport system was developed for handling large swine during cardiovascular research studies. The major design criteria provided for comfortable, low stress restraint of the swine, safety for laboratory personnel and ability to perform a wide variety of hemodynamic and echocardiographic measurements in the standing, supported standing and sedated, or in Panepinto sling positions. A head gate is provided for venipuncture procedures, and an auxiliary feeding and watering front panel can replace the head gate for use of the system as a post-operative "recovery room". Using this system animals weighing 22 to 150 kg can be easily managed. PMID- 1623727 TI - Rectovaginal fistula with atresia ani in three kittens. AB - Rectovaginal fistula with atresia ani was diagnosed in 3 kittens. Physical abnormalities included abdominal distension, bulging of the perineum, and lack of an anal opening. Vaginography was helpful in determining the type of malformation present in 2 cases. In each kitten attempts were made to surgically correct the anatomic malformations. Various post-operative complications such as fecal incontinence, would dehiscence, constipation, and excessive scar tissue formation occurred and are discussed. PMID- 1623728 TI - Mycoplasma felis pleuritis in two show-jumper horses. AB - Mycoplasma felis was identified as the cause of acute pleuritis in 2 show-jumping horses. The pleural exudate was proteinaceous, contained large numbers of neutrophils, and had a markedly increased lactate concentration. M. felis was isolated in pure culture from pleural fluid. Rising serum antibody titers to M. felis as well as a precipitous decline in titers to equine influenza virus were demonstrated in both horses. Pleural effusion in both horses and a pneumothorax detected in one of the horses resolved following a single drainage of pleural fluid and intravenous fluid, antibiotic, and analgesic therapy. PMID- 1623729 TI - Intestinal myxosarcoma in a thoroughbred mare. AB - A large fibrotic mass originating from the cecal base was discovered upon surgical exploration of the abdomen in a Thoroughbred mare with a history of chronic colic and weight loss. The mass protruded intraluminally resulting in partial obstruction. Surgical excision was not feasible due to the location of the mass and the inability to exteriorize it adequately from the abdominal cavity. The mass was fibrous with a shiny, gelatinous material present throughout the neoplasm. Histologically, large confluent spaces filled with mucopolysaccharides were identified by staining with Alcian blue. The diagnosis of myxosarcoma was based upon finding of atypical fibroblastic cells, mucinous stroma, local invasiveness, and metastasis to the regional lymph nodes. Myxomatous tumors have not previously been documented to occur in the equine intestinal tract. PMID- 1623730 TI - A leg restraint system for prevention of peripheral edema and limb trauma in swine. PMID- 1623731 TI - Hypoglycemia and hepatic ischemic necrosis after small intestinal incarceration through the epiploic foramen in a horse. AB - A 16-year-old stallion was presented to the Louisiana State University Veterinary Teaching Hospital for evaluation of acute abdominal pain. Physical examination and diagnostic procedures indicated a strangulating obstruction of the small intestine. At exploratory celiotomy, a strangulating incarceration of the jejunum through the epiploic foramen was found. The incarcerated small intestine was reduced, then resection of the nonviable bowel and anastomosis performed. After surgery, the horse exhibited clinical signs and laboratory findings associated with hypoglycemia and died in spite of emergency treatment. On post-mortem examination, a large thrombus was present in the portal vein at the level of the epiploic foramen and the liver had multiple large infarcted areas. The post operative signs of hypoglycemia and necropsy findings of widespread hepatic ischemic necrosis are complications of epiploic foramen incarceration of the small intestine not previously reported and may in part explain the high mortality rate described for this lesion. PMID- 1623732 TI - Intraluminal hemorrhage from small intestinal ulceration in two cows. AB - Two adult Holstein cows were admitted with signs of acute gastrointestinal hemorrhage. Abomasal ulceration was diagnosed tentatively in both cows, but was later ruled out in 1 cow that had an abomasotomy performed through a right paramedian approach. Both cows failed to respond to treatment of blood loss and hypovolemic shock and became recumbent; one cow died and the other was euthanatized. Post-mortem examination determined the source of hemorrhage in both cows to be ulcerated small intestine with severe intraluminal hemorrhage. The cause of ulceration was undetermined. Small intestinal hemorrhage should be considered in cattle with signs of acute gastrointestinal hemorrhage. PMID- 1623733 TI - The teniae of the equine intestinal tract. AB - At several locations along the equine cecum and colon, the outer longitudinal portion of the tunica muscularis is gathered into discrete bands of smooth muscle and connective tissue called "teniae". In this study, the disposition of the teniae ceci and coli was traced along the equine intestinal tract. It was discovered that, in several instances, arrays of teniae converge toward the valves and sphincters which separate the various intestinal compartments. The teniae may also provide support for and directionality to, peristaltic contraction waves. The tissue proportions of the teniae vary in different locations. The tenia libera lateralis of the ventral colon is rich in elastic connective tissue, while that of the right dorsal colon is primarily composed of smooth muscle. This may reflect the different responsibilities of these two compartments. The teniae are innervated and their smooth muscle cells are joined by many gap junctions. The connective tissue constituents afford intestinal support while yielding to intestinal distension. The smooth muscle and neural elements may foster active tenial participation in peristalsis. This premise must be tested by electrophysiological experimentation. Further experimentation is also necessary to ascertain whether injury to the teniae might predispose a horse to colic. PMID- 1623734 TI - Bronchoalveolar lavage in the study of asthma. PMID- 1623735 TI - Endoscopic management of bronchial stenosis after double lung transplantation. AB - Double lung transplantation with bilateral bronchial sutures is an increasingly popular therapeutic alternative for endstage, bilateral, septic pulmonary disease; however, surgical outcome has been hampered by mechanical complications at the level of the airway anastomoses. In our institution, therefore, the protocol for surveillance includes frequent flexible fiberoptic and rigid bronchoscopy under general anesthesia in all patients. Since 1988, there were 24 double lung transplantations (mean age, 19 yr) performed at the University of Marseille Hospitals using bilateral sutures without omental wrapping. Nineteen patients had cystic fibrosis; of the ten individuals (53 percent) with cystic fibrosis who ultimately developed bronchial stenosis, six required therapeutic endoscopic intervention including dilatation or Nd:YAG laser resection. Five patients required endobronchial silicone stents. Statistically significant risk factors for postsurgical airway narrowing included young age (mean, 14.3 yr vs 24.0 yr in patients without stenosis) and prolonged mechanical ventilation prior to transplant (all five patients ventilated before surgery developed stenosis). Results of interventional bronchoscopy were good, and an excellent level of physical activity was maintained in most patients. A team familiar with all aspects of therapeutic bronchoscopy is essential to ensure proper management of airway complications in patients after lung transplantation. PMID- 1623736 TI - Ventricular function in snorers and patients with obstructive sleep apnea. AB - We hypothesized that intermittent hypoxemia and increased ventricular afterload due to obstructive apnea during sleep (OSA) would cause chronic left ventricular dysfunction. Overnight polysomnography, M-mode and two-dimensional echo-Doppler studies while awake were performed on 51 consecutive snorers, 30 with OSA and 21 without apnea. Patients with previous myocardial infarction, awake hypoxemia or hypercapnia, or other causes of nocturnal hypoxemia were excluded. Echo-Doppler measurements included end-diastolic right and left ventricular dimensions and wall thickness, indices of left ventricular systolic performance (fractional shortening, ejection fraction and ejection time and diastolic performance, (isovolumic relaxation time, ratio of peak early [E] to late [A] diastolic transmitral flow and mitral pressure half-time). Both OSA patients and nonapneic snorers were of similar age. Although OSA patients were heavier, had a greater apnea-hypopnea index, and significant nocturnal hypoxemia, their echo-Doppler measurements were within normal limits and were not significantly different from nonapneic snorers. It is concluded that isolated obstructive sleep apnea does not cause chronic left ventricular dysfunction. PMID- 1623737 TI - Glucose homeostasis. Comparison between hypothermic and normothermic cardiopulmonary bypass. AB - STUDY OBJECTIVE: Disturbance in blood glucose homeostasis during cardiac surgery may cause visceral and metabolic alterations. Hypothermic CPB induces glucose and hormonal changes. As normothermic CPB is used at some institutions, a comparison of blood glucose and plasma hormones between hypothermic and normothermic CPB was performed. DESIGN: Prospective nonrandomized study. SETTING: University cardiac center. PATIENTS: Twenty-two nondiabetic adults undergoing elective coronary bypass and/or valvular surgery. INTERVENTIONS: Group 1 (n = 12) underwent hypothermic CPB (25 degrees C) and group 2 (n = 10) normothermic CPB (37 degrees C). In both groups nonpulsatile CPB was achieved with a membrane oxygenator and dextrose-free crystalloid priming. Dextrose was not administered during surgery but was infused postoperatively (125 mg/kg/h). MEASUREMENTS AND RESULTS: Eight blood samples were drawn during the period of arrival in the operating room (control) to the third postoperative hour. During hypothermic CPB in group 1, blood glucose level increased to 154 +/- 20 mg/dl (mean +/- SD) associated with a decrease in plasma insulin and an increase in epinephrine, despite a decrease in cortisol and growth hormone. During rewarming, the blood glucose value continued to increase (to 197 +/- 35 mg/dl) associated with an increase in glucagon, growth hormone and catecholamines, despite a 374 percent increase in insulin. During CPB in group 2, insulin, glucagon, cortisol and catecholamines were significantly higher than during hypothermic CPB so that the blood glucose level was not significantly different between the two groups during CPB. Blood glucose value was higher in group 1 than in group 2 at closure of the chest (208 +/- 30 vs 175 +/- 19 mg/dl, respectively, p less than 0.02) and at the third postoperative hour (271 +/- 30 vs 221 +/- 51 mg/dl, p less than 0.01). In both groups, however, the postoperative increase in blood glucose was accompanied by a similar increase in insulin, cortisol and catecholamines but glucagon was lower after hypothermic CPB. CONCLUSIONS: Hyperglycemia occurred perioperatively in cardiac surgery with dextrose-free priming both during hypothermic and normothermic CPB but normothermic CPB resulted in a slow and steady increase in both glucose and insulin concentrations without the major perturbations that occurred with hypothermic CPB. Postoperatively, higher blood glucose was observed in the hypothermic CPB group. PMID- 1623738 TI - A two-bag system for continuous measurement of oxygen uptake. AB - Collection of mixed expired gas in a bag has been a classic method for the estimation of VO2 during the steady state but has not been employed during unsteady state exercise in part because there is a need for suspending the acquisition of data during the period of gas analysis unless many bags are used. In this study a two-bag system is described in which one bag fills while the other is analyzed. Bag volume is under the control of the operator, and we employed volumes of 30 to 50 L. Thirty-one subjects were studied with this circuit in a progressive treadmill test. Although VO2 could be falsely elevated during periods of overbreathing, this source of error could be identified and its effect reduced if VO2 was plotted against both ventilation and power requirement. Plateau values of VO2 were identified only in six subjects and the ventilatory threshold in 16. PMID- 1623739 TI - Elevation of plasma truncated elastase alpha 1-proteinase inhibitor complexes in patients with inflammatory lung diseases. AB - Human neutrophil elastase plays an important role in the development of several inflammatory lung diseases; however, there have been relatively few investigations using plasma samples. In this report, we describe alterations in the plasma elastase:alpha 1-PI complex in patients with chronic obstructive pulmonary disease (COPD) (15 cases), COPD with infection (8), diffuse panbronchiolitis (DPB) (8), bronchiectasis (9), pneumonia (10), and the adult respiratory distress syndrome (ARDS) (14), and in 15 normal volunteers. The elastase:alpha 1-PI complex concentration was determined by an enzyme-linked immunosorbent assay. Western immunoblot analysis of the elastase:alpha 1-PI complex was also performed. Plasma elastase:alpha 1-PI complex was also performed. Plasma elastase:alpha 1-PI complex levels in patients with COPD with infection (504 micrograms/L +/- 93 micrograms/L) were significantly higher, as compared with those with COPD but without infection (118 micrograms/L +/- 9 micrograms/L) and normal volunteers (122 micrograms/L +/- 4 micrograms/L). Increased complex concentrations were also found in patients with DPB and bronchiectasis (643 micrograms/L +/- 222 micrograms/L and 558 micrograms/L +/- 198 micrograms/L, respectively) as compared with normal volunteers. Increased complex concentrations were also found in patients with pneumonia and ARDS (450 micrograms/L +/- 101 micrograms/L and 1,400 micrograms/L +/- 438 micrograms/L, respectively). Western immunoblot analysis using anti-alpha 1-PI antibody and antineutrophil elastase antibody showed two types of elastase:alpha 1-PI complexes, one with a molecular weight of 60,000 daltons (60 kilodaltons [KD]) and the other at 50,000 daltons (50 KD). Although the native 80-KD elastase:alpha 1-PI complex was detected in bronchoalveolar lavage fluid, it was not found in plasma. In summary, these results demonstrated that levels of the truncated complex were increased in patients with various inflammatory lung diseases. This truncated form may play an important role in the pathophysiology of inflammatory processes. PMID- 1623740 TI - Cerebral vascular responsiveness in chronic hypercapnia. AB - To assess the responsiveness of the cerebral vessels to chronic hypercapnia, we measured middle cerebral artery flow velocity by transcranial Doppler ultrasound in 20 normal subjects and in 14 COLD patients before and after stimulation by progressive hypercapnia (rebreathing test) or by intravenous administration of an acetazolamide bolus. The results showed no statistically significant difference in baseline flow velocity between the normal subjects and the COLD patients. The COLD patients showed a reduced cerebral vascular responsiveness to both stimuli. Cerebral blood flow is normal in chronic hypercapnia and the mechanism by which compensation is achieved leads to a decrease in cerebral vascular responsiveness. PMID- 1623741 TI - Effects of body position and age on membrane diffusing capacity and pulmonary capillary blood volume. AB - The effects of body position and age on the membrane diffusing capacity (Dm), pulmonary capillary blood volume (Vc), and the single breath carbon monoxide diffusing capacity (Dco) were evaluated in the erect (sitting) and supine positions in 16 normal young men (under 40 years old, younger group) and in 13 older men (over 40 years old, older group). Dm and Vc were estimated by several measurements of the Dco at increasing alveolar oxygen tension (PAO2). The results showed that Dco, Dm, Vc, and Kco (Dco corrected by alveolar volume) decreased with age in both positions. The differences in Dco, VC, and Kco between the two positions (supine minus the erect position) also decreased with age. The mechanisms of the increases in Dco in the supine position remain to be explained but may be due to a change in pulmonary capillary shape from an elliptical (erect position) to a circular configuration (supine position) since Vc increased more than Dm on assuming the supine position. The findings may be of clinical importance since many physicians have attempted to utilize a reduction in the positional change in Dco as a potential marker of disease. PMID- 1623742 TI - The role of bronchoscopy in the diagnosis of pulmonary tuberculosis in patients at risk for HIV infection. AB - The present study was undertaken to clarify the role of bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) in the diagnosis of pulmonary tuberculosis in patients at risk for human immunodeficiency virus (HIV) infection. We retrospectively identified 31 patients at risk for HIV who proved to have Mycobacterium tuberculosis on culture of at least one pulmonary specimen. All had pulmonary symptoms but initial sputum smears negative for acid-fast bacilli (AFB). All underwent fiberoptic bronchoscopy (FOB), including BAL and TBB; postbronchoscopy sputum was also collected in 19 patients. A specimen was considered to yield an immediate diagnosis when positive for AFB either on smear or histologic study; granulomas alone were considered positive when no other causes were identified. Overall, an immediate diagnosis was made by bronchoscopic specimens in 15 (48 percent) of 31 cases. TBB was the sole positive specimen in seven patients (23 percent). For comparison, similar specimens from 40 patients in whom M avium complex (MAC) grew on culture were also evaluated. An immediate identification of AFB was made in only four patients (10 percent). We conclude that the finding of AFB on staining of any pulmonary specimen is highly suggestive of tuberculosis, rather than MAC, and warrants institution of antituberculosis therapy. Of all bronchoscopic specimens, TBB provides the highest yield for an immediate diagnosis of tuberculosis. PMID- 1623743 TI - Evaluation of breath-by-breath measurement of respiratory gas exchange in pediatric exercise testing. AB - In adults, breath-by-breath analysis has been used for measuring respiratory gas exchange during exercise. The present study evaluates the validity and reproducibility of this method in children. In 21 patients with various types of congenital heart disease, steady state exercise testing was performed on a motor driven treadmill. Based on simultaneous measurements of VO2, VCO2, VE and R, comparisons were made between the breath-by-breath and Douglas bag methods. No significant differences were found between both methods for any of the variables. In seven other patients the reproducibility of cardiorespiratory variables during exercise was assessed. No significant difference was found for the cardiorespiratory variables during any of the tests and the coefficients of variation were comparable to data obtained in adults. It is concluded that the breath-by-breath method for measuring respiratory values can be applied in children with an acceptable degree of validity and reproducibility. PMID- 1623744 TI - Reliability of a respiratory history questionnaire and effect of mode of administration on classification of asthma in children. AB - Because there is no consensus definition of asthma for epidemiology, we have examined the reliability of a questionnaire and the effect of its mode of administration on classification of asthma in children. A symptom history questionnaire was parent self-administered and then readministered within three months by a nurse. The questions of diagnosed asthma, cumulative wheeze, and recent wheeze (wheeze in the previous 12 months) were more repeatable than questions of night cough, but 7 percent of children changed diagnosed asthma category, 13 percent changed cumulative wheeze category, and 9 percent changed recent wheeze category at second questionnaire. Because the numbers who changed from symptom positive to negative roughly equalled the changes from negative to positive, prevalence estimates were not affected. Methods of measuring asthma with greater precision are urgently needed. Because of reporting bias, epidemiologic information collected by current questionnaires should be treated with some caution. PMID- 1623745 TI - Risk factors for reduced pulmonary function in women. A possible relationship between Pi phenotype, number of children, and pulmonary function. AB - Smoking and severe deficiency of protease inhibitor (Pi Z phenotype) both contribute significantly to the development of chronic obstructive pulmonary disease (COPD). The role of moderate Pi deficiency (Pi MZ phenotype) remains controversial. During a community-wide study of respiratory health which included 1,633 individuals, of whom 897 were women, we measured forced vital capacity (FVC), forced expired flow in 1 s (FEV1), midmaximum expired flow rate (MMFR), flow rate at 50 percent of FVC (Vmax50%) and flow rate at 25 percent of FVC above residual volume (Vmax25%). We carried out Pi phenotyping on 544 of these women, including 22 who were Pi MZ or FZ phenotypes. There were no statistically significant differences in mean pulmonary function (pf) values between the Pi MZ and Pi M women. Examination of residual pf values (difference between observed and expected) by means of multiple multivariate regression analysis revealed that in Pi MZ women, FEV1/FVC%, MMFR, Vmax50%, and Vmax25% had significantly greater values with increasing numbers of children, whereas there was no relationship in the Pi M women. These results suggest that some factors may interact differently in individuals with Pi M and MZ phenotypes. In addition, the results suggest that pregnancy or pregnancy-induced increased Pi levels may have significant effects on the pulmonary health of Pi MZ women. PMID- 1623746 TI - Survival of patients with severe thoracic spine deformities receiving domiciliary oxygen therapy. AB - Scoliosis can lead to respiratory failure and premature death. Alveolar hypoventilation is a dominant cause and artificial ventilation at home (AVH) is probably the treatment of choice. It has been suggested that long-term domiciliary oxygen therapy (LTO) is of little value because of the worsening of hypercapnia. We analyzed survival and predictors of death among 80 patients with scoliosis and other severe thoracic spine deformities receiving LTO for chronic hypoxia. The survival rate was higher in patients under the age of 65 (p = 0.01) and in patients without concomitant pulmonary or airways disease. Likewise, the survival rate was higher in patients with a PaCO2 of greater than 7.4 kPa than in patients with a lesser degree of hypoventilation and hypercapnia (p less than 0.05). The risk of developing life-threatening hypercapnia during well-controlled LTO appeared to be small. In younger patients without complicating disease, long term survival was achieved with LTO, but with time, an increasing proportion of the patients changed to AVH, with or without LTO. PMID- 1623747 TI - Use of arm crank exercise in the detection of abnormal pulmonary gas exchange in patients at low altitude. AB - BACKGROUND: The measurement of arterial blood gases, P(A-a)O2 and VD/VT, during cycle ergometry is the "gold standard" for the assessment of pulmonary gas exchange. However, some patients are unable to perform cycle ergometry because of other medical problems. STUDY OBJECTIVE: To determine whether arm crank exercise could be used to reliably detect gas exchange abnormalities compared to cycle ergometry. PARTICIPANTS: Fifteen patients with a variety of pulmonary disorders, who were referred for exertional dyspnea. DESIGN: All patients performed maximal arm crank and cycle exercise. Arterial blood gases, VO2, VCO2, and VE were measured at rest and during exercise. RESULTS: Compared to peak cycle exercise (mean +/- SD), PaO2 (85 +/- 14 vs 75 +/- 13 mm Hg), SaO2 (94 +/- 2 vs 91 +/- 4 percent), VD/VT (0.21 +/- 0.07 vs 0.19 +/- 0.08), and pH (7.37 +/- 0.04 vs 7.34 +/- 0.03) were significantly higher during peak arm crank exercise. The P(A-a)O2 (18 +/- 13 vs 29 +/- 12 mm Hg) was narrower, and PaCO2 (29 +/- 3 vs 29 +/- 4 mm Hg) and PAO2 (104 +/- 4 vs 103 +/- 4 mm Hg) were similar. Six patients had normal gas exchange during cycle exercise at low altitude (P[A-a]O2 less than or equal to 27 mm Hg, PaO2 greater than or equal to 65 mm Hg, VD/VT less than or equal to 0.18) and nine were abnormal. Utilizing criteria specific for arm crank at low altitude, the same six patients had normal gas exchange (P[A-a]O2 less than or equal to 13 mm Hg, PaO2 greater than or equal to 85 mm Hg, VD/VT less than or equal to 0.26), and the remaining nine were abnormal. The P(A-a)O2 during peak arm crank was the most useful criterion in identifying patients with abnormal gas exchange. CONCLUSION: Proposed criteria for arm crank exercise testing accurately identified all patients with normal and abnormal pulmonary gas exchange during cycle exercise. The data from the present study suggest that arm crank can be an acceptable alternative exercise testing modality for the assessment of pulmonary gas exchange. PMID- 1623748 TI - The diagnosis of acute pulmonary embolism in patients with chronic obstructive pulmonary disease. AB - The clinical features and noninvasive tests, including ventilation perfusion (V/Q) lung scans, were assessed in 108 patients with chronic obstructive pulmonary disease (COPD) suspected of having pulmonary embolism (PE). Twenty-one (19 percent) of 108 patients had PE. In the majority of patients, it was impossible to distinguish between patients with and without PE by clinical assessment alone. However, when a high clinical index of suspicion was present, PE was confirmed by angiography in three of three patients, but the V/Q scan was of intermediate probability. No roentgenographic abnormalities distinguished between PE and no PE. There was no difference between the alveolar-arterial oxygen gradients in either group, nor was there evidence of a reduction in the PaCO2 in patients with PE who had prior hypercapnia. Among the 108 patients with COPD, high, intermediate, low, and normal/near normal probability scans were present in 5 percent, 60 percent, 30 percent, and 5 percent, respectively. The frequency of PE in these V/Q scan categories was five (100 percent) of five, 14 (22 percent) of 65, two (6 percent) of 33, and zero (0 percent) of five, respectively. In conclusion, in the majority of patients, the V/Q scan diagnosis is usually intermediate and such patients require further investigational studies, including angiography. However, among the few patients who demonstrated a high probability lung scan, there was a high positive predictive value for PE effectively avoiding the need for further studies. In those patients with low probability or near normal/normal V/Q scans, the negative predictive value was not lower than the general hospital population. PMID- 1623749 TI - Changes in crackle characteristics during the clinical course of pneumonia. AB - Recorded crackling lung sounds of 11 patients with pneumonia were studied with phonopneumography, FFT spectrography and time-expanded waveform display. The sounds were recorded on average six days after the onset of pneumonia and the recording was repeated two to four days later. In the first recording the crackles were coarse and midinspiratory. The patients with unilateral pneumonia had a significant difference in the upper frequency limit of inspiratory sound of the FFT spectrum between the healthy and diseased lung (p less than 0.01). In the second recording, the beginning of crackling had shifted later (p less than 0.01) and the end point of crackling also became later (p less than 0.05). The largest deflection width of the individual crackles became shorter (p less than 0.05). The results indicate that the pneumonic crackles vary markedly during the clinical course of pneumonia. The duration of the individual crackles became shorter and the timing of the crackles shifted toward the end of inspiration. PMID- 1623750 TI - Gastric tonometry in patients with sepsis. Effects of dobutamine infusions and packed red blood cell transfusions. AB - We wanted to determine the efficacy of dobutamine infusions and Prbc transfusions on splanchnic tissue oxygen utilization by measuring gastric pHi. Physiologic parameters and pHi measurements via the use of a gastric tonometer were obtained in 21 septic patients before and after the administration of a dobutamine infusion (5 micrograms/kg/min) or the transfusion of two units of Prbc. Subsets of measurements with normal (greater than 7.32) and with low (less than 7.32) pHi were separately analyzed for each intervention. In the dobutamine low pHi group, pHi increased significantly from 7.16 +/- 0.03 to 7.24 +/- 0.03 (n = 9, p less than 0.05). In contrast, pHi failed to increase in the Prbc low pHi subgroup (7.16 +/- 0.05 to 7.17 +/- 0.04 [n = 10, p greater than 0.80]). We conclude that dobutamine rather than Prbc transfusions should be administered to reverse gastric intramucosal acidosis. PMID- 1623751 TI - Respiratory muscle strength in hypothyroidism. AB - To investigate respiratory muscle strength in patients with hypothyroidism, global respiratory muscle strength was assessed by measuring mouth pressure during PImax and PEmax efforts. Maximum pressures, VC, FEV1, FVC, T3, T4, and TSH were measured in 43 hypothyroid patients. Measurements were made before and three months after replacement therapy with thyroxine. The results showed that the mean value of PImax and PEmax increased after treatment. Significant change was found in the mean value of VC, FEV1, and FVC after treatment but not in the FEV1/FVC ratio. A highly statistically significant linear relationship was found between PImax and TSH and between PEmax and TSH as well as between PImax and T3 and PEmax and T3. We conclude that hypothyroidism affects respiratory muscle strength and that this weakness is linearly related to thyroid hormone levels. Respiratory muscle weakness is present in both inspiratory and expiratory muscles and is reversible with treatment. PMID- 1623752 TI - Lung density and lung mass in emphysema. AB - Mean lung density (dm) and radiologic (VLx) lung volume can be calculated using CT scan data. As many emphysematous patients are overdistended, the analysis of dm alone could be meaningless. However, lung mass (m) can be calculated as the product of dm and VLx. Twenty-four patients suspected of mild or severe emphysema as judged by roentgenographic and physiologic examinations as well as 16 healthy subjects were included in the protocol. They all underwent both a CT scan of the whole lung and functional tests from which the following were derived: airway resistance, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), total lung capacity (TLC), CO transfer capacity, quasi-static compliance at functional residual capacity (FRC), and blood gases. All CT scans were performed at the FRC of each patient. The dm was lower in emphysema patients than in healthy subjects, as m was greater in patients than in healthy subjects; 1,303 +/ 398 g and 997 +/- 133 g, respectively. Although dm values were significantly correlated to FEV1, FEV1/FVC, and TLC, m values were not correlated to any of these functional indices. Unexpectedly, these results show that most patients (22/24) with emphysema have a normal or increased lung mass. Normal or above normal m values might be due to oversecretion in some patients. Nevertheless, the synthesis of new tissue due to chronic inflammation is the most likely explanation that could account for this finding. PMID- 1623753 TI - Long-term oxygen therapy. When to leave well enough alone. PMID- 1623754 TI - Clinical utility of thoracoscopy. PMID- 1623755 TI - Role of oxygen debt in the development of organ failure sepsis, and death in high risk surgical patients. AB - In a series of 253 high-risk surgical patients, we measured the oxygen consumption (VO2) at frequent intervals before, during, and immediately after surgical operations and calculated the rate of VO2 deficit from the measured VO2 minus the VO2 need estimated from the patient's own resting preoperative control values corrected for both temperature and anesthesia. The calculated oxygen deficit was related to multiple organ failure, complications, and outcome. The 64 patients who died all had organ failure; their cumulative VO2 deficit averaged 33.2 +/- 4.0 L/m2 (+/- SEM) at its maximum, which occurred 17.8 +/- 2.2 h after surgery. In the 31 survivors with organ failure, the cumulative VO2 deficit averaged 21.6 +/- 3.7 L/m2 at its maximum, which occurred 10.1 +/- 2.7 h after surgery (p less than 0.05). In the 158 survivors without organ failure or major complications, the maximum cumulative VO2 deficit averaged 9.2 +/- 1.3 L/m2 at 4.1 +/- 0.6 h after surgery (p less than 0.05). In a prospective randomized clinical trial, a protocol group maintained at supranormal hemodynamic and oxygen transport values had significantly reduced oxygen debt (7.6 +/- 3.4 L/m2 vs 17.3 +/- 6.8 L/m2; p less than 0.05), fewer organ failures, and lower mortality (4 percent vs 33 percent; p less than 0.05) compared with a control group maintained at normal hemodynamic values. The data demonstrate a strong relationship between the magnitude and duration of the VO2 deficit in the intraoperative and early postoperative period and the subsequent appearance of organ failure and death. The latter may be reduced when oxygen debts were prevented or minimized by augmenting naturally occurring compensations that increased oxygen delivery. PMID- 1623756 TI - Elevation of cardiac output and oxygen delivery improves outcome in septic shock. AB - Septic shock is characterized by hypoperfusion and tissue energy defects. We prospectively evaluated the therapeutic benefit of augmenting cardiac output and therefore oxygen delivery (DO2) on mortality in patients with septic shock. Twenty-five patients were randomized to a normal treatment (NT) group and 26 patients were randomized to an optimal treatment (OT) group. All patients had a clinically evident site of infection, sepsis as defined by a systemic response to the infection, and shock indicated by systemic hypoperfusion. Patients were treated during the initial 72 h by an algorithm differing only in the end point of resuscitation. The cardiac index (CI) was increased to 3.0 L/min/m2 in the NT group and to 6 L/min/m2 in the OT group. There were no significant differences in cardiorespiratory parameters in the NT and OT groups on entrance into the study. During treatment, CI averaged 3.6 +/- 0.2 L/min/m2 and DO2 averaged 8.6 +/- 0.8 ml/min/kg in the NT group and CI averaged 5.1 +/- 0.2 L/min/m2 and DO2 averaged 12.2 +/- 0.7 ml/min/kg in the OT group (p less than 0.01). A significant correlation between DO2 and survival was observed. Seventy-two percent of the OT patients died vs 50 percent of the NT patients (p = 0.14). Surviving NT patients stayed 13.7 +/- 3 days in the ICU vs 7.4 +/- 0.6 days (p less than 0.05) for the OT patients. Since some of the NT patients were spontaneously hyperdynamic and some of the OT patients did not achieve their desired end point, patients were arbitrarily subsetted using a midpoint CI of 4.5 L/min/m2. The NT less than 4.5 group had a CI of 3.1 +/- 0.2 L/min/m2 and DO2 of 10.9 +/- 1.0 ml/min/kg while the OT group greater than 4.5 L/min/m2 had a CI of 5.7 +/- 0.2 L/min/m2 and a DO2 of 13.8 +/- 0.7 ml/min/kg (p less than 0.01). Mortality in the NT less than 4.5 group was 74 percent as compared with 40 percent in the OT greater than 4.5 group (p less than 0.05). PMID- 1623757 TI - Modification of oxygen extraction ratio by change in oxygen transport in septic shock. AB - To help clarify the oxygen uptake/transport (VO2/TO2) relationship and because the oxygen extraction ratio (OER) and TO2 share no common variable such as cardiac index, we examined the changes in OER when TO2 was decreased in 12 patients with sepsis in whom a PEEP trial was performed. From zero end-expiratory pressure (ZEEP) to PEEP (12 +/- 3 cm H2O), a significant increase in OER from 30 +/- 10 percent to 38 +/- 12 percent (p less than 0.005) was observed, and individual percentage changes in OER were well correlated with individual percentage changes in TO2. The VO2 measured (VO2m) by respiratory gas analysis was unchanged, while VO2 calculated by the Fick equation (VO2f) decreased, suggesting a mathematical coupling between VO2f and TO2. Patients with hyperlactacidemia (n = 5) exhibited the same relationships between OER, VO2m, and TO2 as those without hyperlactacidemia. Our results suggest an adaptive response in the OER when TO2 is decreased in patients with established septic shock. PMID- 1623758 TI - Effects of PEEP on respiratory mechanics after open heart surgery. AB - Respiratory dysfunction, particularly atelectasis, is common after open heart surgery. Routine use of PEEP (5 to 10 cm H2O) in these patients has been advocated. We studied the effects of different levels of PEEP on respiratory mechanics in ten mechanically ventilated open heart surgery patients in the immediate postoperative period. PEEP was studied in increasing increments and decreasing decrements. This procedure was repeated three times. Flow, tidal volume, and airway pressure were measured. We used the rapid airway occlusion technique to determine static compliance of the respiratory system (Cst,rs) and intrinsic PEEP (PEEPi). The changes in end-expiratory lung volume (delta EELV) were measured with respiratory inductive plethysmography. Recruitment of lung units (Vrec) was estimated as the difference in lung volume between PEEP and zero end-expiratory (ZEEP) for the same static inflation pressure (15 cm H2O). We found that (1) Cst,rs at ZEEP was significantly reduced (60 +/- 2 ml/cm H2O); (2) while PEEP of 5 cm H2O did not cause significant recruitment, higher levels of PEEP (10 to 15 cm H2O) were effective; (3) Cst,rs, Vrec, and delta EELV were higher during stepwise PEEP decrease; (4) after the first and second stepwise PEEP increase-decrease run, there was a small persistent increase in EELV and Cst,rs at ZEEP. No further changes were found after the third run. We conclude that after open heart surgery, PEEP less than 10 cm H2O is not effective to reopen atelectatic lung units. PMID- 1623759 TI - P wave height during incremental exercise in patients with chronic airway obstruction. AB - We examined changes in P wave height in lead 2 of an ECG obtained during progressive exercise in 23 patients with COPD, and measured both P wave changes and pulmonary hemodynamics during exercise at a constant workload corresponding to approximately 50 to 60 percent of VO2 max in nine patients. The P wave response to exercise (delta P/delta VO2, %/ml/min), estimated by the relationship between percentage of change in P wave height and VO2, was significantly greater (p less than 0.01) in 15 patients who had a decrease in PaO2 with exercise (group A) than eight patients who did not have a fall in PaO2 with exercise (group B). There was a significant negative correlation between change in PaO2 and change in P wave height from rest to maximal exercise (r = -0.68, p less than 0.001). Oxygen therapy in nine patients in group A reduced the increase in P wave height during exercise. Furthermore, change in P wave height from rest to exercise correlated significantly with that of mean pulmonary artery pressure (r = 0.75, p less than 0.01). These results suggest that increase in P wave height during exercise in COPD patients is related partly to oxygen desaturation during exercise, and continuous measurement of P wave change may be useful for noninvasively predicting the pulmonary vascular pressure response to exercise. PMID- 1623760 TI - Evaluation of respiratory inductive plethysmography in the measurement of breathing pattern and PEEP-induced changes in lung volume. AB - STUDY OBJECTIVE: To assess the accuracy of the respiratory inductive plethysmography in the measurement of PEEP-induced changes in end-expiratory lung volume during mechanical ventilation and its accuracy and stability in the measurement of ventilation during controlled mechanical ventilation and spontaneous breathing. DESIGN: An open comparison between two methods using a criterion standard. Either a pneumotachometer (mechanically ventilated patients) or a spirometer (spontaneously breathing subjects) was used as the reference method. SETTING: Tertiary care center; a multidisciplinary intensive care unit and a metabolic research unit. PATIENTS: Six mechanically ventilated, paralyzed postoperative open heart surgery patients, six spontaneously breathing COPD patients, and eight healthy volunteers. INTERVENTIONS: Stepwise increases and reductions of PEEP from zero to 12 cm H2O during controlled mechanical ventilation; repeated validation of the calibration of the respiratory inductive plethysmography (RIP) in both mechanically ventilated and spontaneously breathing subjects. MEASUREMENTS AND RESULTS: The baseline drift of the RIP in vitro was 10 ml/150 min and in a ventilated model it was 20 ml/150 min. In mechanically ventilated patients, the mean error of the calibration after 150 min was within +/- 5 percent. Change in end-expiratory lung volume (EELV) during the stepwise increase of PEEP up to 12 cm H2O was 849 +/- 136 ml with the RIP and 809 +/- 125 ml with the pneumotachometer (PT), and during the stepwise reduction of PEEP it was 845 +/- 124 ml and 922 +/- 122, respectively (not significant [NS]. The mean difference between methods in the measurement of change in EELV was -6.6 +/- 3.5 percent during increasing and 6.6 +/- 6.7 percent during decreasing PEEP (NS). Both in mechanically ventilated and spontaneously breathing subjects, the difference between methods was significant for VT and VT/TI. The difference in VT was -2.2 +/- 0.2 percent during mechanical ventilation, -1.1 +/- 0.5 percent in spontaneously breathing COPD patients, and 2.9 +/- 0.4 percent in healthy volunteers (NS between groups). CONCLUSIONS: The RIP is sufficiently accurate for the measurement of PEEP-induced changes in EELV during controlled mechanical ventilation. The accuracy of tidal volume measurement is similar during mechanical ventilation and spontaneous breathing. The calibration of the RIP is stable enough for bedside monitoring of changes in lung volumes. PMID- 1623761 TI - Drug-induced pulmonary disease. An update. PMID- 1623762 TI - The significance of irregular opacities on the chest roentgenogram. AB - Scanty irregular opacities are not uncommonly observed on the chest roentgenogram in the absence of interstitial fibrosis of the lungs. In such circumstances the irregular opacities, when present, tend to be relatively scanty and seldom, if ever, exceed an ILO category of 1/1. They are found in association with cigarette smoking, especially when emphysema is also present. The development of irregular opacities is also related to exposure to various mineral and other dusts, and although their prevalence increases with cumulative dust exposure, in general the type of dust, whether fibrogenic or relatively inert, seems to be of little moment. The presence of irregular opacities remains a troublesome confounding factor in epidemiologic studies of both dust-exposed and nonexposed populations. The morbid anatomic changes that occur in the lungs of nondust-exposed workers and which are responsible for the development of irregular opacities in the chest roentgenogram remain unknown. PMID- 1623763 TI - Upper lobe cystic lesions and cough in a young woman. PMID- 1623764 TI - Chronic, progressive, bibasilar infiltrates in a woman with constipation. PMID- 1623765 TI - Ethical relationships between drug companies and the medical profession. PMID- 1623766 TI - The effects of pharmaceutical firm enticements on physician prescribing patterns. There's no such thing as a free lunch. AB - We examined the impact on physician prescribing patterns of pharmaceutical firms offering all-expenses-paid trips to popular sunbelt vacation sites to attend symposia sponsored by a pharmaceutical company. The impact was assessed by tracking the pharmacy inventory usage reports for two drugs before and after the symposia. Both drugs were available only as intravenous preparations and could be used only on hospitalized patients. The usage patterns were tracked for 22 months preceding each symposium and for 17 months after each symposium. Ten physicians invited to each symposium were interviewed about the likelihood that such an enticement would affect their prescribing patterns. A significant increase in the prescribing pattern of both drugs occurred following the symposia. The usage of drug A increased from a mean of 81 +/- 44 units before the symposium to a mean of 272 +/- 117 after the symposium (p less than 0.001). The usage of drug B changed from 34 +/- 30 units before the symposium to 87 +/- 24 units (p less than 0.001) after the symposium. These changed prescribing patterns were also significantly different from the national usage patterns of the two drugs by hospitals with more than 500 beds and major medical centers over the same period of time. These alterations in prescribing patterns occurred even though the majority of physicians who attended the symposia believed that such enticements would not alter their prescribing patterns. PMID- 1623767 TI - Hemodynamic effects of amrinone in a canine model of massive pulmonary embolism. AB - Amrinone, an inotrope with vasodilating properties, is of potential use in managing the right ventricular failure and pulmonary vasoconstriction induced by massive pulmonary embolism (PE). Therefore, to determine the hemodynamic effects of amrinone in a canine model of massive PE, autologous blood clot was infused into ten dogs (eight treated and two control animals) in an amount sufficient to decrease mean systemic arterial pressure (MAP) by at least 25 percent. This resulted in an increase in mean pulmonary artery pressure (MPAP) from 13.4 +/- 3.7 mm Hg to 44.4 +/- 4.8 mm Hg (p less than 0.01), a decrease in MAP from 122 +/ 9.5 mm Hg to 35.6 +/- 9.8 mm Hg (p less than 0.01), and a decrease in cardiac output from 2.73 +/- 0.834 L/min to 1.22 +/- 0.61 L/min (p less than 0.01). Amrinone was administered in an initial bolus of 0.75 mg/kg followed by an infusion of 7.5 micrograms/kg/min, which resulted in significant hemodynamic improvement in all subjects, with a fall in MPAP to 35.3 +/- 5.1 mm Hg (p less than 0.01), an increase in MAP to 98.1 +/- 31.1 mm Hg (p less than 0.01), and an increase in cardiac output to 2.01 +/- 0.7 L/min (not significant) at 5 min. Cardiac output continued to increase to 2.56 +/- 0.16 L/min (p less than 0.01) at 35 min. We conclude that amrinone alleviated pulmonary hypertension, systemic hypotension, and low cardiac output in a canine model of massive PE. PMID- 1623768 TI - Ciliary function, cell viability, and in vitro effect of ribavirin on nasal epithelial cells in acute rhinorrhea. AB - Nasal epithelial (NE) cells were collected from the nasopharynx of 25 individuals with symptomatic colds and 27 healthy volunteers (controls), and ciliary beat frequency (CBF) was assessed by microscopy employing video motion analysis techniques. Baseline CBF was statistically significantly elevated in the group with colds compared to the control group (14.6 +/- 1.5 Hz [mean +/- SD] vs 13.8 +/- 0.9 Hz; p = 0.02). After four days of incubation in culture, there was a significant decrease in the CBF in both groups, with a change from baseline of 1.9 Hz for the cold group, compared to 1.0 Hz for the control group (p = 0.0001). The in vitro addition of ribavirin at 500 micrograms/ml to NE cells from individuals with colds preserved the viability of the cells and maintained the CBF at baseline values. Twenty-four (96 percent) of 25 ribavirin-treated specimens from the cold group survived for four days in culture, compared with 17 (68 percent) of 25 untreated cold specimens. In addition, the ribavirin-treated cells had a mean CBF of 14.2 +/- 1.3 Hz, compared with 12.7 +/- 1.9 Hz for the untreated cell samples (p = 0.0005). Ribavirin had no effect on NE cells from the control group. These results suggest that ribavirin in a concentration of 500 micrograms/ml may have some benefit in the treatment of acute rhinorrhea. PMID- 1623769 TI - Polysomnography in acutely ill intensive care unit patients. PMID- 1623770 TI - Abdominal placement of tube thoracostomy due to lack of recognition of paralysis of hemidiaphragm. AB - Tube thoracostomy is an invasive procedure that carries a risk of complications. We report a patient with liver cirrhosis, ascites and large left-sided pleural effusion, in whom a trocar type chest tube was inserted at the seventh left intercostal space in the midaxillary line. Chest roentgenogram revealed that the drainage tube was placed into the abdominal cavity because of a misrecognized elevation of the left hemidiaphragm. This case demonstrates that the placement of a tube thoracostomy requires caution in the identification of possible abnormalities which can lead to dangerous complications. PMID- 1623772 TI - Pleural effusion as first sign of extramedullary plasmacytoma. AB - A patient with mediastinal EP with extension to pleural spaces and subsequent pleural effusion is described. The finding of many plasma cells in pleural fluid led to diagnosis. Similar histologic findings such as multiple myeloma and immunoblastic lymphoma were ruled out by clinical approach and immunochemistry, respectively. This pleural effusion represents the first case described caused by EP. PMID- 1623771 TI - Acute eosinophilic pneumonia due to toxocariasis with bronchoalveolar lavage findings. AB - A previously healthy young man presented with breathlessness, diffuse pulmonary infiltrates on the chest x-ray film, and a high degree of peripheral blood eosinophilia. Analysis of bronchoalveolar lavage (BAL) fluid showed 64 percent eosinophils. A diagnosis of toxocariasis was eventually reached on the basis of a positive enzyme-linked immunosorbent assay (ELISA) for Toxocara canis. The routine performance of the ELISA test for Toxocara in the diagnostic approach to pulmonary infiltration with eosinophilia could reveal an undetermined, sometimes unsuspected, number of cases of adult toxocariasis with pulmonary involvement. A high degree of eosinophilia in the differential cell count of BAL fluid may eventually prove to be a useful clue in favor of such a diagnosis. PMID- 1623773 TI - Transesophageal echocardiography to diagnose and demonstrate resolution of an acute massive pulmonary embolus. AB - A 54-yr-old man presented with acute respiratory failure and hemodynamic collapse. Acute massive pulmonary embolus was confirmed with visualization of the thrombus by transesophageal echocardiography. Successful resolution after thrombolysis was confirmed by a repeat study. Transesophageal echocardiography can be used for both diagnosis and assessment of therapy in select cases of acute massive pulmonary embolism. PMID- 1623774 TI - Heart-lung transplantation in a 16-month-old infant. AB - A 16-month-old boy who had a heart-lung transplantation is doing well 16 months postoperatively. The HLT can be a successful treatment for very young patients. Most of the postoperative management can be assessed with noninvasive techniques. Normally, the allograph grows with the recipient. PMID- 1623775 TI - Long-term severe pulmonary hypertension associated with right atrial myxoma. AB - An 18-year-old black woman presented with marginally compensated right heart failure, severe pulmonary hypertension, tricuspid incompetence, and right atrial myxoma. Catheterization suggested a substantial reactive component to her P-HTN, especially to nifedipine. Initial management consisted of excision of two right atrial myxomas and tricuspid annuloplasty, and postdischarge management with nifedipine, 30 mg four times daily. Emergency pulmonary thromboendarterectomy was required two weeks later for acute cor pulmonale. It is suggested that concomitant procedures are mandatory in this setting because of the otherwise accelerated adverse pathophysiology of obliterative pulmonary vascular obstructive disease. PMID- 1623776 TI - Amyloid heart disease manifested by systemic arterial thromboemboli. AB - Amyloid heart disease characteristically produces a stiff heart syndrome whereby diastolic filling is impaired yet systolic function is well preserved. We report two patients with this pattern of amyloid heart disease, both of whom developed cardiogenic thromboemboli. The rarity of this complication is striking given the pathophysiologic bases of amyloid heart disease. Investigation of contributing causes revealed that the phenomena appeared to represent the cumulative effects of disorders producing stasis, endothelial disturbance, and probable abnormalities in blood coagulability, the classic Virchow's triad revisited. Understanding of the pathophysiologic basis of this event leads to specific suggestions for workup and management in this patient population. PMID- 1623777 TI - Massive intraoperative pulmonary embolism. AB - Intraoperative massive pulmonary embolism is extremely rare. We describe such a case in a patient treated for a prolonged period preoperatively with intravenous heparin after an acute myocardial infarction and unsuccessful attempt at angioplasty, emphasizing that the problem should be borne in mind to facilitate expeditious and appropriate management. A clue to the diagnosis is interruption of venous return that is not due to a kink in the cannulae. PMID- 1623778 TI - High dose rate brachytherapy improves resectability in squamous cell lung cancer. AB - A 44-year old man with squamous cell carcinoma of the left lower lobe extending to the mucosa of the main carina, was treated with high dose rate brachytherapy prior to surgery. A significant reduction of tumor infiltration was achieved allowing a radical pneumonectomy instead of a sleeve pneumonectomy with resection of the main carina. He remains disease-free after a follow-up period of 43 months. PMID- 1623779 TI - The effect of short-term nasal CPAP on Cheyne-Stokes respiration in congestive heart failure. AB - We studied male patients (BMI = 27.6 +/- 3.4, mean +/- SD), mean age 54.1 +/- 8.9 years, with stable NYHA class 3-4 congestive heart failure (CHF) (LVEF = 24.3 +/- 11.5 percent) and normal daytime arterial blood gas values. These patients underwent three consecutive nights of full polysomnography; adaptation, control, and treatment with nasal CPAP. Each night's study was followed during the day by cognitive testing and multiple sleep latency tests (MSLT). The purpose of the study was to document the effect of nasal CPAP on these variables. The main findings of the study showed no significant differences between control and treatment nights with respect to the amount of Cheyne-Stokes respiration (CSR) observed, the nocturnal oxygenation, or sleep quality. Both subjective and objective measures of sleep quality showed no change from night to night. In addition, the degree of cognitive functioning and daytime sleepiness (as measured by MSLT) showed no significant differences between control and treatment nights. We conclude that short-term treatment with nasal CPAP in patients with CHF does not improve either CSR, nocturnal oxygenation, or sleep quality. Furthermore, most of our patients did not tolerate nasal CPAP therapy. PMID- 1623780 TI - Bilateral proximal pulmonary artery aneurysms simulating hilar adenopathy. AB - Proximal pulmonary artery aneurysms (PAAs) are rare. Most are associated with secondary pulmonary hypertension or a variety of rare systemic disorders. An asymptomatic adult patient presented with bilateral hilar enlargement on a routine chest roentgenogram. Computed tomography of the chest revealed 5 cm bilateral proximal PAAs with a normal pulmonary trunk. The clinician should consider proximal PAA in the differential diagnosis of hilar enlargement. PMID- 1623781 TI - Implantation metastasis of carcinoma after percutaneous fine-needle aspiration biopsy. AB - Implantation of malignant cells along the needle tract is an extremely rare but potential complication following percutaneous needle aspiration biopsy of malignant lesions. Percutaneous fine-needle aspiration biopsy (FNAB) has recently received more attention for cytologic diagnosis of bronchogenic carcinoma because of its high diagnostic yield, simplicity, and low morbidity. On the other hand, dissemination of cancer cells by needle aspiration biopsy can change a potentially resectable localized lung cancer to an unresectable one. We report two cases: one patient underwent FNAB of a metastatic left adrenal mass that seeded a paraspinal muscle implantation of malignant cells that subsequently developed a tumor mass, and the second patient had tumor cell implantation in the chest wall after FNAB of a pleural-based adenocarcinoma of the lung. The theoretical and practical importance of tumor cell spread along the needle tract is discussed. Because of its rare incidence, however, this complication should not affect the use of needle aspiration biopsy in bronchogenic carcinoma, although care should be undertaken during the procedure. PMID- 1623782 TI - Erythropoietin therapy obviates the need for recurrent transfusions in a patient with severe hemolysis due to prosthetic valves. AB - Erythropoietin has been proved extremely effective in ameliorating the anemia of chronic renal failure and is currently under intensive investigation. We describe a patient with severe anemia and secondary hemochromatosis due to prosthetic valves, who has been successfully treated with erythropoietin. During 12 months' follow-up, an acceptable hemoglobin level was maintained without any need for blood transfusions; in addition, there was evidence indicating regression of hemochromatosis. This patient illustrates that erythropoietin therapy might prove beneficial for similar cases. PMID- 1623783 TI - Intramyocardial calcification in the elderly. A diagnostic and therapeutic puzzle. AB - A 70-year-old woman presented with anular and progressive intramyocardial calcification within a five-year period. She had become increasingly symptomatic with mitral regurgitation and coronary insufficiency during the same period. The subvalvular (mitral) calcified intramyocardial mass was found to be "grumous atherosclerosis." This was obliterated while the mitral valve was replaced with a prosthetic valve and the coronary arteries were bypassed x3. She is surviving and well four years postoperatively. PMID- 1623784 TI - Left coronary dominance due to direct continuation of the left anterior descending to form the posterior descending coronary artery. AB - Continuation of the left anterior descending to form the posterior descending artery is rarely observed. We describe the first patient with this variant in whom the coronary artery extends beyond the crux, supplying branches to the atrioventricular node and both atrioventricular grooves. PMID- 1623785 TI - Silent maladie de Roger. AB - A patient with no cardiac murmur was found to have a ventricular septal defect by Doppler echocardiography yet no evidence of pulmonary or right ventricular hypertension. This array of findings is distinctly unusual and appears to be at odds with the clinical teachings concerning small ventricular septal defects. PMID- 1623786 TI - Severe hypoxia due to ventilation-perfusion mismatch caused by aortic arch aneurysm. AB - We report a very rare case of hugh aortic arch aneurysm associated with aortic restenosis, which caused severe hypoxia due to ventilation-perfusion mismatch by compression of the left main bronchus and the right pulmonary artery. Aortic arch replacement was performed under circulatory arrest and deep hypothermia in addition to aortic valve replacement as a redo operation, and consequently such hypoxia was relieved. PMID- 1623787 TI - Pacemaker-induced friction rub and apical thrill. AB - A patient with acute myocardial infarction developed a loud systolic sound and apical thrill. Doppler ultrasound excluded interventricular septal rupture and significant mitral or tricuspid regurgitation. Auscultatory abnormalities disappeared after removal of a temporary pacing electrode, suggesting that the friction it created with intracardiac structures was responsible for these findings. PMID- 1623788 TI - Adenosine deaminase in pleural effusion. PMID- 1623789 TI - Reversible dilated cardiomyopathy due to growth hormone deficiency. PMID- 1623790 TI - Sudden apnea following attempted central line placement. PMID- 1623791 TI - Preventive pulmonary medical education. PMID- 1623792 TI - Morbidity and duration of ICU stay after cardiac surgery. A model for preoperative risk assessment. AB - Although risk factors for mortality after cardiac surgery have been identified, there is no widely applicable method for readily determining risk of postoperative morbidity based on preoperative severity of illness. The goal of this study was to develop a model for stratifying the risk of serious morbidity after adult cardiac surgery using readily available and objective clinical data. After univariate analysis of risk factors in 3,156 operations, 11 variables were identified as important predictors by logistic regression (LR) analysis and used to construct an additive model to calculate the probability of serious morbidity. Reliable correlation was found between a simplified additive model for clinical use and the LR model. The clinical and logistic models were then tested prospectively in 394 patients and demonstrated a pattern of increasing morbidity with ascending scores similar to that predicted by the reference group. Increasing clinical risk score was also associated with a greater frequency of individual complications as well as prolongation of ICU stay. This study demonstrates that it is feasible to design a simple method to stratify the risk of serious morbidity after adult cardiac surgery. With further prospective multicenter refinement and testing, such a model is likely to be useful for adjusting severity of illness when reporting outcome statistics as well as planning resource utilization. PMID- 1623793 TI - Don't get run over by the bandwagon. PMID- 1623794 TI - Recovery of pulmonary function in patients undergoing extended left ventricular assistance. AB - Heart transplantation should follow the implantation of a left ventricular assist device (LVAD) only after optimal postoperative recovery of pulmonary function. We reviewed hospital records of 12 patients who underwent extended (greater than 30 days) left ventricular support before transplantation to determine the rate of return of pulmonary function. The mean cardiac index and pulmonary capillary wedge pressure returned to normal in all patients within three days after LVAD implantation. The mean pulmonary artery pressure and pulmonary vascular resistance decreased but did not return to normal. The mean central venous pressure remained elevated throughout the first month but decreased by the time of transplantation. Supplemental oxygen requirements and peak airway pressures improved, and ten of the 12 patients were extubated by the fifth postoperative day. Preoperative roentgenographic evidence of pulmonary edema was present in eight patients, and pulmonary hilar prominence was present in the remaining four patients. Roentgenographic resolution of the pulmonary edema occurred slowly, persisting for one week after surgery in seven of eight patients. Ten patients were able to exercise strenuously 30 days after surgery, and 11 were returned to excellent condition before undergoing heart transplantation. Although the hemodynamic status in these patients significantly improved shortly after LVAD implantation, optimal recovery of pulmonary function required several weeks. Therefore, we advocate delaying transplantation after LVAD implantation to allow optimal pulmonary recovery. PMID- 1623795 TI - Reoperation, emergency and urgent open cardiac surgery in Jehovah's Witnesses. AB - Progressive advances in perfusion technology and perioperative supportive management have made it possible for members of the Jehovah's Witnesses religious group to undergo open cardiac operations with remarkable safety. However, hospital mortality remains high in (1) patients requiring reoperation (in whom both technical and bleeding problems tend to be more frequent) and (2) patients with significantly compromised cardiac performance requiring urgent or emergency operation. Employing a number of perioperative measures designed to minimize blood loss and maintain hematocrit levels (including use of the recently available recombinant human erythropoietin in two patients whose cases are reported herein), 13 reoperations and five urgent or emergency operations were performed. The one death in the entire series occurred in a patient (reoperation group) who died of a cerebrovascular accident of presumed embolic etiology, having undergone combined debridement of a stenotic heavily calcified aortic valve and a second coronary artery revascularization procedure. None of the patients required surgical exploration for bleeding. We suggest that currently available methodology permits Jehovah's Witnesses to undergo reoperation, emergency surgery, or urgent open cardiac operation at a level of risk not dissimilar to that seen in patients who permit use of homologous blood and products in their treatment. PMID- 1623796 TI - Differential cell analysis in bronchoalveolar lavage fluid from pulmonary lesions of patients with tuberculosis. AB - To obtain information on the cellular reactions to Mycobacterium (M) tuberculosis in the lung, we analyzed the cells in bronchoalveolar lavage (BAL) fluid from pulmonary lesions in comparison with those in BAL fluid from nonaffected regions of the lungs, and control lungs, and in peripheral blood of patients with tuberculosis. Neutrophils and lymphocytes were increased in number in BAL fluid from affected lesions of the lungs of patients with miliary tuberculosis and patients with active pulmonary tuberculosis compared with those in BAL fluid from control patients, but the number of alveolar macrophages was decreased in BAL fluid from tuberculous lesions. However, the numbers of these cells were not changed in the BAL fluid from nonaffected regions of the lungs of patients with active or inactive pulmonary tuberculosis. The numbers of lymphocytes were decreased and the numbers of monocytes were increased in peripheral blood from patients with miliary tuberculosis and with active tuberculosis, indicating inverse changes in the numbers of lymphocytes and monocytes in the peripheral blood to those in the BAL fluid of patients with tuberculosis. These results indicate characteristic redistributions of immune or inflammatory cells in response to infection with M tuberculosis and suggest that these changes are important for understanding the pathophysiology of pulmonary tuberculosis. PMID- 1623797 TI - Imaged thoracoscopic lung biopsy. AB - Imaged thoracoscopic surgery is a technique utilized to operate on the intrathoracic organs without making a formal thoracotomy incision. Eleven patients underwent lung biopsy with this procedure and each had markedly reduced postoperative pain. Each patient resumed preoperative activity levels within one week of discharge from the hospital. Besides thoracotomy and thoracoscopy, imaged thoracoscopic surgery provides another option for approaching the intrathoracic organs. PMID- 1623798 TI - Correlation of bronchoalveolar lavage findings to severity of Pneumocystis carinii pneumonia in AIDS. Evidence for the development of high-permeability pulmonary edema. AB - We correlated bronchoalveolar lavage findings with the clinical course and outcome of Pneumocystis pneumonia. Forty-eight patients with AIDS and a confirmed diagnosis of P carinii pneumonia were studied. Patients with additional pulmonary infections were excluded. On the basis of BAL findings, they were divided into those with a low neutrophil count (less than 5 percent) and those with a high neutrophil count (greater than or equal to 5 percent). Sixteen patients with AIDS but without PCP served as a control group. All BAL fluid samples from the control group showed a low neutrophil count. The group with PCP and a high neutrophil count had more severe respiratory compromise and greater morbidity than the group with PCP and a low neutrophil count. Mortality rate was not different. The group showing a high BALF neutrophil count also showed a higher BALF protein concentration, a higher ratio of BALF protein concentration to plasma protein concentration, and the presence of alpha 2-globulins compared with other groups. These findings suggest that increased alveolar-capillary permeability occurs during severe PCP. PMID- 1623799 TI - Nontuberculous mycobacteria in adult patients with cystic fibrosis. AB - Because patients with cystic fibrosis (CF) may be predisposed to airway infections with unusual microorganisms, we screened the sputum of adult CF patients for mycobacterial organisms. Acid-fast bacilli (AFB) smears and mycobacterial culture were performed on 297 sputum specimens from 87 patients. Cultures for mycobacteria were frequently overgrown with other bacteria; 22.6 percent of cultures were contaminated. Despite this limitation of mycobacterial culture, 17 patients had at least one positive culture for a Mycobacterium other than tuberculosis (MOTT). Eleven patients were positive for Mycobacterium avium intracellulare (MAI), two for MAI and M chelonei, three for M chelonei, and one for M fortuitum. None was positive for M tuberculosis. Patients with CF with MOTT were similar to patients with CF without MOTT; only a slightly different (older) age distribution was recognized. The clinical significance of MOTT was difficult to determine in any individual patient, but patients with positive AFB smears appeared more likely to suffer pathogenic effects. We conclude that MOTT is frequently recovered from adult CF patients in the southeastern United States. A specific risk factor for colonization and/or pathogenic infection in this patient group was not evident. The general prevalence and clinical pathogenesis in CF patients in the United States remains to be determined. PMID- 1623800 TI - Diagnostic value of telescoping plugged catheters in HIV-infected patients with pulmonary infiltrates. AB - To assess the diagnostic value of telescoping plugged catheters (TPC) in human immunodeficiency virus (HIV)-infected patients with pulmonary infiltrates (PI), we performed a prospective clinical study in 71 episodes of fever and PI in 66 HIV-infected patients (five patients had two different episodes of fever and PI). A control group of 12 HIV-infected patients with fever and normal chest roentgenogram was also studied. In all patients and prior to antibiotic treatment (except in mechanically ventilated patients), a TPC using quantitative cultures (cutoff point established at 10(3) CFU/ml) and a bronchoalveolar lavage (BAL) sampling were performed via fiberoptic bronchoscope. The overall incidence of bacterial pneumonia in the study group was 21 percent. The TPC cultures resulted in a microbiologic diagnosis of bacterial pneumonia in eight patients (11 percent) from the study group and in one patient (8 percent) from the control group. The TPC sensitivity in diagnosing bacterial infections was 53 percent and specificity was 76 percent. Negative predictive value was 85 percent and positive predictive value was 38 percent. By means of BAL, 35 episodes from the study group and two from the control group were diagnosed as nonbacterial or mycobacterial pulmonary infections. Considering TPC and BAL together, diagnosis was performed in 42 cases of PI (59 percent). Twenty percent (17/83) of HIV infected patients suffered from bacterial colonization of their lower airways (a TPC culture greater than or equal to 10(3) CFU/ml without clinical evidence of bacterial infection). We conclude that the combined use of TPC and BAL may be useful in HIV-infected patients with PI, since this combined use allows the proper diagnosis of bacterial and nonbacterial infections, thereby increasing the overall diagnostic accuracy. To distinguish bacterial colonization from pulmonary infection in HIV-infected patients with PI, the cutoff point of quantitative cultures of TPC may be 10(4) CFU/ml. PMID- 1623801 TI - Comparison of prognosis of pulmonary diseases caused by Mycobacterium avium and by Mycobacterium intracellulare. AB - A total of 55 patients with pulmonary disease caused by Mycobacterium avium and by Mycobacterium intracellulare were compared for their prognosis. Causative mycobacteria were identified by the DNA probes (Gen-Probe) method. Of the 55 patients, 28 had pulmonary disease caused by M avium and the remaining 27, by M intracellulare. Of the former group, four patients had progressive disease, and three of them died during the observation period. In contrast, only one of the latter group had progressive disease. On the other hand, only one of the former group was cured. In contrast, six of the latter group were cured, showing the closure of cavity and the disappearance of mycobacteria from the sputum. The prognosis of pulmonary disease caused by M avium appears to be worse than that caused by M intracellulare. PMID- 1623802 TI - The effects of enalapril and spironolactone on terbutaline-induced hypokalemia. AB - OBJECTIVE: To investigate whether enalapril (E) 10 mg and spironolactone (S) 100 mg attenuate the hypokalemic effect of inhaled terbutaline (T). DESIGN: Randomized single-blind crossover. Subjects received the following treatment combinations: (a) placebo (P), (b) T alone, (c) T + E, or (d) T + S. SETTING: University Department of Clinical Pharmacology. PARTICIPANTS: Twenty healthy volunteers (ten male, ten female) of mean age 22.8 +/- 3.1 years. MAIN OUTCOME MEASURES: Serum potassium, magnesium, ECG changes (R-R interval, T wave, and QTc interval) for 4 h after terbutaline inhalation. MAIN RESULTS: Baseline serum potassium levels were higher following prior treatment with E and S; P, 3.78 mmol/L (3.67 to 3.88); T + E, 3.93 mmol-1 (3.82 to 4.03); and T + S, 4.03 mmol/L (3.93 to 4.14) (p less than 0.05). Mean potassium concentrations over 4 h were also higher following prior treatment with E and S; T, 3.58 mmol/L (3.54 to 3.63); T + E, 3.68 mmol/L (3.64 to 3.72) (p less than 0.05); and T + S, 3.73 mmol/L (3.68 to 3.78) (p less than 0.01). CONCLUSIONS: Enalapril and spironolactone protect against the fall in serum potassium over 4 h by elevating baseline potassium concentration. These potassium-sparing drugs, however, should not be used to prevent the hypokalemic and electrocardiographic sequelae of inhaled beta 2-agonists. PMID- 1623803 TI - Spontaneous clinical and hemodynamic improvement in patients on waiting list for heart transplantation. AB - Heart transplantation is currently the most effective therapy for patients with severe heart failure due to dilated cardiomyopathy, although long-term survival without transplantation has been described in a few patients. We have identified five patients with severe heart failure who experienced a significant clinical and hemodynamic improvement while they were waiting for heart transplantation. At initial assessment, all five patients were symptom-class 4; left ventricular end diastolic pressure was 33 +/- 4 mm Hg, left ventricular ejection fraction was 0.20 +/- 0.01, left ventricular end-systolic volume was 130 +/- 3 ml/min/m2, and cardiac index was 2.1 +/- 0.1 L/min/m2. These patients showed a marked improvement at two to ten months after initial assessment, while they were waiting for a donor heart. After a follow-up of 10 to 31 months (mean follow-up, 20 months), the five patients were still alive and their clinical and hemodynamic condition remained stable. On the contrary, survival was less than 15 percent at six months for the remaining patients with indications for heart transplantation but in whom transplant could not be performed because of the existence of contraindications or lack of donors; all these patients were dead at 18 months after initial assessment. The five patients who developed spontaneous favorable outcome showed a trend to have higher serum sodium values, shorter symptomatic history, lesser need for intravenous inotropic support, and better response to medical therapy than the other patients. Our findings suggest that some patients with transplants could have experienced a sustained and spontaneous clinical and hemodynamic recovery with medical therapy alone, although it seems currently difficult to identify patients with this favorable outcome. PMID- 1623804 TI - BOOP in Europe. PMID- 1623805 TI - Bronchiolitis obliterans organizing pneumonia: definition and clinical features. AB - There are several bronchiolar diseases with different pathologic and clinical findings. Idiopathic BOOP is a distinct entity consisting of a flu-like illness, late inspiratory crackles, patchy infiltrates roentgenographically, and physiologically decreased vital capacity and diffusing capacity. Response to corticosteroid therapy is good and relapse does not occur if sufficient therapy is given. Bronchiolitis obliterans organizing pneumonia is an appropriate description of this entity. The term is specific because it includes bronchioles and alveoli and excludes disorders involving only alveoli such as organizing pneumonitis or organizing diffuse alveolar damage. The term is general enough to include a sufficient number of patients with a homogenous disorder. Furthermore, the entity can be described to clinicians and pathologists throughout the world in such a fashion that patient care and research can be standardized. Researchers from different centers studying the cause or utilizing treatment protocols are able to discuss a single BOOP entity rather than comparing results of a heterogeneous group of many different types of interstitial lung disorders. This will lead to breakthroughs in discovery of etiologic causes and new effective therapeutic regimens. PMID- 1623806 TI - Clinical features of BOOP in Japan. PMID- 1623807 TI - High-resolution computed tomographic features of bronchiolitis obliterans organizing pneumonia. PMID- 1623808 TI - Bronchoalveolar lavage cell findings in patients with BOOP and related diseases. PMID- 1623809 TI - Pathologic aspects of bronchiolitis obliterans organizing pneumonia. PMID- 1623810 TI - Differential diagnosis of bronchiolitis obliterans organizing pneumonia. AB - The disease concept of idiopathic BOOP has emerged from a study of many open lung biopsy cases of diffuse infiltrative lung disease. The histopathologic features of idiopathic BOOP have several components: bronchiolitis obliterans, organizing pneumonia, accumulation of foamy cells in the peripheral air spaces, and interstitial infiltration of mononuclear cells. These pathologic findings are nonspecific and many conditions show such a BOOP pattern. Idiopathic BOOP has been discussed in the context of bronchiolitis obliterans, organizing pneumonia, and interstitial pneumonia. While clinically idiopathic BOOP has a relatively broad spectrum of manifestation, BOOP stands as a clinicopathologic disease entity among diffuse infiltrative lung diseases of unknown etiology. PMID- 1623811 TI - Bronchiolitis obliterans organizing pneumonia. A British view. PMID- 1623812 TI - Cryptogenic organizing pneumonitis. The North American experience. AB - Cryptogenic organizing pneumonitis is a clinical and pathologic syndrome characterized by a "pneumonia-like" illness with excessive proliferation of granulation tissue within small airways and alveolar ducts associated with chronic inflammation in the surrounding alveoli. The duration of illness prior to lung biopsy is short, usually less than 2 months, and it is markedly different from that of IPF. Interestingly, unlike in IPF where the patient has difficulty remembering the exact onset of symptoms, patients with COP are frequently very specific about the timing of their disease onset. This is because the disease onset is recent and is often dramatic with the development of a severe flulike illness, ie, cough, fever, malaise, fatigue, and weight loss. Inspiratory crackles are frequently present on chest examination. Pulmonary function is usually impaired with a restrictive defect being most common. Gas exchange abnormalities are extremely common with a reduction in Dco and resting hypoxemia being almost universal findings. The roentgenographic manifestations are quite distinctive with a pattern of bilateral, diffuse but inhomogeneous, ground-glass or alveolar opacities being present in the majority of the cases. Bronchoalveolar lavage findings are nonspecific but usually reveal a lymphocytosis. The response to corticosteroid treatment is quite favorable and death from progressive disease is uncommon in COP, especially if treatment is instituted early in the course of the disease. In our experience, the cases with the worse prognosis are those associated with another disease process, in particular, connective tissue disorders like rheumatoid arthritis. In fact, these patients are prone to develop a rapidly progressive form of BOOP with a clinical course similar to the "Hamman Rich syndrome." Recurrences are relatively frequent, consequently, withdrawal of treatment should be done with extreme caution. Corticosteroids have been the conventional initial treatment of COP, although to our knowledge, there are no controlled clinical trials to support it use. Antibiotics are not effective in treating this syndrome. Thus, based solely on our experience and that of others, we believe that high-dose corticosteroid therapy should be used to treat COP, usually initiated with 1 to 1.5 mg/kg/day (using ideal body weight) not to exceed 100 mg/day. Prednisone is given as a single oral dose in the morning. We recommended maintaining this dose for 4 to 8 weeks. If the patient's condition is stable or improved, the prednisone dosage is gradually tapered to 0.5 to 1 mg/kg/day (using ideal body weight) for the ensuing 4 to 6 weeks.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1623813 TI - Risks and rewards of resin bonded bridges: a review of the literature and some conclusions. PMID- 1623814 TI - Etidronate for vertebral osteoporosis after the menopause. PMID- 1623815 TI - Terbinafine for dermatophytes in skin and nail. PMID- 1623816 TI - Management of early breast cancer. PMID- 1623817 TI - Postscript: starting oral contraceptives. PMID- 1623818 TI - [The difficult process of a woman's subjectivation. Sermon on 1. Samuel 1 to 2, 11]. PMID- 1623819 TI - ["Siamese twins". The connection between sterility and reproductive technics]. PMID- 1623820 TI - [Treatment of infertility by in-vitro fertilization]. PMID- 1623821 TI - [Laboratory methods for the treatment of women who desire children]. PMID- 1623822 TI - [Help me to have children; if not I shall die. Report of one afflicted]. PMID- 1623823 TI - [Nursing problems in the care of in vitro fertilized women]. PMID- 1623824 TI - [Fertilization in vitro from the chaplain's viewpoint]. PMID- 1623825 TI - [Artificial insemination and ethics. Thoughts on the ethical justification of a progressive medical technology]. PMID- 1623826 TI - [Reproduction medicine and feministic opposition]. PMID- 1623827 TI - [Multiple births and their problems from the view point of the neonatologist]. PMID- 1623828 TI - [Law for the protection of embryos. Targets and methods of legal regulations for dealing with human life in vitro]. PMID- 1623829 TI - [Workloads of male and female nurses in Austria]. PMID- 1623830 TI - [Transfer of duty at the bedside. Report of experiences]. PMID- 1623831 TI - [Primary care--an alternative?]. PMID- 1623832 TI - [The theory of nursing--further need of clarification]. PMID- 1623833 TI - [Pulmonary thrombendarterectomy in thromboembolic pulmonary hypertension. The indications and early results]. AB - Pulmonary thrombendarterectomy was performed in 32 patients (14 men and 18 women; mean age 38 +/- 15 years) with thromboembolic pulmonary hypertension (New York Heart Association stage III: n = 22; stage IV: n = 10). The preoperative arterial pO2 averaged 59 +/- 11 mm Hg; pulmonary vascular resistance (PVR) and mean pressure (MPAP) were increased to 1,045 +/- 430 dyn.s.cm-5 and 53 +/- 12 mm Hg, respectively. The perioperative death rate was 22% (7 of 32). In the 25 survivors the pulmonary hypertension was reduced to a PVR of 194 +/- 75 dys.s.cm-5, MPAP of 28 +/- 6 mm Hg. Subsequent re-examination in 15 patients (NYHA stage I: n = 14, stage II: n = 1) after a mean of 17 +/- 5 months demonstrated an arterial pO2 averaging 92 +/- 6 mm Hg and, in 14 patients, echocardiographically normal right ventricular volumes and function. The primary success was confirmed in eight patients by haemodynamic measurements. These data indicate that thrombendarterectomy can effectively treat the increased PVR in most patients at all stages of the disease. PMID- 1623834 TI - [Endocrinously active parathyroid cysts. Their diagnosis by the determination of intact parathormone in the cyst fluid]. AB - A 53-year-old woman with recurrent nephrolithiasis was found to have hypercalcaemia of 3.12 mmol/l and an intact parathormone level of 166 pg/ml, indicating primary hyperparathyroidism. Preoperative ultrasound examination to localize the parathyroid adenoma revealed a clear fluid-containing cyst in the right lobe of the thyroid. The aspirated fluid had an intact parathormone level of 306 pg/ml, twice that in serum. The cyst was removed surgically. 14 days postoperatively calcium and parathormone levels in serum had become normal without any calcium administration. Measuring the concentration of intact parathormone in the aspirated cyst fluid made possible not only the distinction from a thyroid cyst but also the precise preoperative localization of the parathyroid cyst. PMID- 1623835 TI - [Liver transplantation in erythrohepatic protoporphyria]. AB - A 51-year-old man had for 5 years been known to have erythropoietic protoporphyria. GPT levels were raised up to 40 U/l, gamma-GT up to 120 U/l. After lengthy exposure to sun radiation an erythema with blisters, abdominal discomfort and jaundice developed (total bilirubin 7.3 mg/dl) and biliary liver cirrhosis with portal hypertension and splenomegaly were diagnosed. Because the acute hepatobiliary complications were not improved by conservative treatment (daily 750 mg ursodeoxycholic acid and 12 g colestyramine), an orthotopic liver transplantation was performed without complication. The excised liver showed small nodular parenchymal transformation and contained reddish brown protoporphyrin pigment in the hepatocellular cytoplasm, the Kupffer cells, the canaliculi and in some biliary ducts. Bilirubin and transaminase levels in blood became normal after the transplantation, as did the urinary excretion of coproporphyrin. However, isomer I was still dominant. The protoporphyrin level in erythrocytes and plasma remained elevated. After a symptom-free interval of one year biochemical and histological tests demonstrated protoporphyrin-induced damage in the transplanted liver. PMID- 1623836 TI - [Fever: the expression of a cytokine-mediated defense reaction]. PMID- 1623837 TI - [When and how should a fever be reduced?]. PMID- 1623838 TI - [The risk profile of low-dose methotrexate in the therapy of chronic polyarthritis]. PMID- 1623839 TI - [The fee in treatment according to the rules of naturopathy. The judgement of the Stuttgart District Court of 1 March 1991]. PMID- 1623840 TI - [Protein C deficiency in ulcerative colitis]. PMID- 1623841 TI - [Acute photodermatosis (sun allergy)]. PMID- 1623842 TI - [The vertical transmission of HIV-1]. PMID- 1623843 TI - Impulse pattern, innervation density and two point discrimination of skin and mucosal afferents in humans. Considerations for a sensory reinnervation of urinary bladder and anal canal in spinal cord lesions. IV (IV). AB - 1. Single fiber action potentials (Ap's) were recorded with 2 pairs of wire electrodes from a coccygeal nerve root. Simultaneous impulse patterns of 3T0 + 6T1 + 3T2 + 11T3 + 5T4 and 4P single skin afferent units were separated by their different Ap wave forms and conduction velocities. For a rapid touch or pin-prick the afferent units fired on average with 2 Ap's. 2. The touch units had most likely the following receptor properties. T1: rapidly adapting, medium high threshold, sensitive to skin traction over a distance of more than 10 cm. T2: rapidly adapting, high threshold. T3: slowly adapting, lowest threshold among T afferents for a light touch with no movement along the skin. T4: slowly adapting, lowest threshold among T afferents for a light touch with a movement component parallel to the skin surface. The T1 to T4 afferent receptors are the PC, RA, SAI and SAII receptors respectively. The correspondence is not safe. 3. With nerve fibre diameter distribution histograms (morph), myelinated fibre numbers, conduction velocity distribution histograms (electro) and Ap occurrence patterns, innervations were determined. With estimated dermatome areas, innervation densities i of skin dermatomes were calculated for nerve fibre diameters larger than 5 microns: i(electro, morph; Co) = (0.6T0 + 1.2T1 + 2.8T2 + 2.4T3 + 1.2T4 + 1.6P)/cm2, i(morph; S4) = (0.4T0 + 1T1 + 0.8T2 + 1.1T3 + 0.5T4)/cm2, i(electro; S4) = 0.4T0 + 2.3T1 + 2.1T2 + 2T3 + 1.5T4)cm2, i(morph; T9) (lateral)) = (0.8 (T0 or hair follicle) + 1.7T1 + 0.9T2 + 0.7T3 + 0.4T4)/cm2. 4. Innervation densities of mucosal afferent units M of urethra, trigonum vesicae and anal canal through S3 and S4 roots had the following lower limits: i(electro; urethra + trigonum) = 2 M/cm2, i(electro; anal canal) = 3 M/cm2. The innervation density of skin like receptors of the anal canal through an S4 ventral root was with i(electro; anal canal) = (0.5T0 + 2.4T1 + 1.6T2 + 1.2T3 + 0.8T4)/cm2 at least as high as the innervation density of the S4 dermatome. The urethra possesses no skin like receptors in the mucosa. Mechanoreceptor afferents of the mucosa (M) of urethra and anal canal had thresholds similar to those of T3 and T4 afferents. 5. The two point discrimination of a volunteer was for a light touch 30 mm in the S3 and S4 dermatomes and reduced to 25 mm with faster and stronger touch. In the direction of the anus and the os coccygeum the two point discrimination reduced to 25 mm.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1623844 TI - The effect of muscle fiber length change on motor units potentials propagation velocity. AB - The influence of the muscle length on the propagation velocity of the extraterritorial action potentials was studied. Single low--threshold motor units (MUs) from m. biceps brachii, both with superficially and deeply situated fibers were investigated. The velocity of excitation propagation decreases with the muscle elongation. This dependence is not so prominent for MUs having more deeply situated fibers. In case of superficial MUs the experimentally obtained values are in better agreement with the core conductor model (v = k.square root of r), than with the linear dependence of the propagation velocity (v) on the muscle fiber radius (r) (v = k.r) observed by Hakansson (1957) on frog muscles. The observed difference between superficial and deep MUs was discussed. At least two factors may be responsible for greater changes of the excitation propagation velocity along the fibers of the superficially situated MUs during the muscle elongation. One possible factor is the essential change in the external resistance due to the decrease of distance from the fibers to the skin surface. The greater change of the muscle length during a passive muscle stretching might be another reason. PMID- 1623845 TI - Peripheral nerve conduction and central motor conduction after magnetic stimulation of the brain in myotonic dystrophy. AB - Central motor conduction time was calculated after magnetic stimulation of the brain in 15 patients with myotonic dystrophy and in 38 healthy voluntaries of the same age. Conventional electromyography and motor and sensory conduction velocities were also performed. Central motor conduction time from vertex to C8 was within the normal range in all patients whereas motor conduction velocity of the peripheral nerve and amplitude of the nerve evoked potentials were slightly reduced in 3 and 2 cases respectively, supporting peripheral nerve involvement in some subjects. Our results suggest that the reported central nervous system involvement in myotonic dystrophy, including the nonspecific white matter lesions showed by magnetic resonance imaging, would not affect the conduction of the corticospinal tracts. Magnetic stimulation on the motor cortex is a painless method to study the central nervous system and apports a satisfactory approximation to central motor pathways conduction. PMID- 1623846 TI - Electrophysiological assessment of spinal cord lesions by means of transcranial cortical stimulation. AB - Central Motor Conduction Time (CMCT) was assessed in 30 healthy volunteers and 22 patients with spinal cord lesions due to compressive, degenerative and demyelinating disease. To obtain the CMCT, electrical Transcranial Stimulation and Percutaneous Spinal Stimulation or F wave calculations were employed. Pyramidal Tract (PT) conduction was always abnormal in the clinically impaired corticospinal tracts of all the studied patients. This results correlated with the degree of muscle weakness specially in those having compressive lesions. Subclinical evidence of pyramidal damage was also observed in two patients with Multiple Sclerosis. As opposed to the other groups, patients with degenerative spinal disease, showed essentially symmetric abnormalities. An important overlap of CMCT slowness was seen among the three studied groups, suggesting that this isolated clue is not valuable enough for aetiological suspicion. Double muscle responses due to single TCS were obtained, during rest, in some patients from each group, but never in controls. This pathological feature, not reported by others, could represent the excitation of indirect corticospinal connections, partially responsible for the residual motor function after PT damage. PMID- 1623847 TI - Brain-stem auditory evoked potentials in supratentorial brain tumors. AB - A group of 42 adult patients with supratentorial brain tumors were studied with computed tomography (CT or/and NMR) and brain-stem evoked potentials (BAEPs). 12 patients had meningiomas and 30 had malignant tumors (gliomas and metastases). The latencies of wave V and of the interpeak latency I-III, III-V and I-V were evaluated both on the lesion side and the opposite side. In meningiomas mean latencies did not show significant differences from normal, while mean latencies in malignant tumors were significantly prolonged, except for the I-III interpeak latency. The results of this study demonstrate that BAEPs may be altered by supratentorial brain tumors. This examination appears to be useful in the monitoring of these lesions after treatment. PMID- 1623848 TI - High frequency vibration induced gating of subcortical and cortical median nerve somatosensory evoked potentials: different effects on the cervical N13 and on the P13 and P14 far-field SEP components. AB - Subcortical and cortical somatosensory evoked potentials (SEP) to median nerve stimulation were recorded before, during and after high frequency (270 Hz) vibration of the fingers 1-3 in 8 healthy subjects. A marked decrease of the amplitude of all potentials was observed. The attenuation of the sensory nerve action potential (SNAP) of the median nerve and the attenuation of SEP components N9, N11 and N13 showed no differences, while the attenuation of the subcortical P14 component was significantly higher. This is in accordance with a generator of the cervical N13 in the interneurons beside the lemniscal pathway. The cortical N20 (post-rolandic) was significantly more decreased in amplitude than P14 while P22 (pre-rolandic) remained reduced in amplitude like P14. An increased latency of the far-field subcortical P14 was observed, while P13 recorded in the same montage remained unchanged in latency. These findings suggest different generators of these peaks. A generator of P14 above the nucleus cuneatus is confirmed. A presynaptic generator of P13 is suspected. PMID- 1623849 TI - Miller Fisher syndrome: etiological significance of serial blink reflexes and MRI study. AB - We studied a patient with Miller Fisher syndrome using a serial MRI and electrophysiological procedures. There were peripheral nerve pathology and CNS dysfunction. In particular, MRI showed a lesion at the level of the 3rd nerve nucleus. PMID- 1623850 TI - Feeding problems in children with congenital heart disease: the impact on energy intake and growth outcome. AB - Cross-sectional data on growth outcome, upper-arm measurements and energy intake have been analysed according to the presence or absence of early feeding problems and poor appetite in 40 children (0.9-13 years) with congenital heart disease (CHD). At the time of study, refusal to eat or poor appetite was reported as a significant problem in 19 children and subnormal height and/or weight were recorded in 11 children. The children ate considerably less calories than recommended for healthy children. The cross-sectional analyses showed that children with poor appetite had significantly (P less than 0.05 and P less than 0.01) lower outcome values of growth and upper-arm measurements than their disabled counterparts with no feeding problems and good appetite. Children with feeding problems also tended to eat less than children without feeding problems. For most parents (65%) feeding of infants and children with CHD involves difficulties, time and anxiety. This study has shown that the parents' experience about feeding problems may be a good predictor for low growth outcome and low voluntary food intake of the child. Whenever feeding problems are reported, nutritional intervention should be offered in order to increase the caloric intake of the child and to develop a sound feeding relationship in the family. PMID- 1623851 TI - Effect of family size and income on the biochemical indices of urban school children of Bangladesh. AB - The relationship between family size and income and the biochemical indices of 242 children (aged from 5 to 12 years) from five schools in Dhaka City, Bangladesh, was investigated. Socio-economic data were collected by questionnaire and blood samples were drawn by visiting each school on a prefixed date. Mean levels of all measures, except for serum zinc, fell within the normal range. Older boys, but not girls (10-12 years of age) had statistically significantly higher haemoglobin, serum protein and serum vitamin A levels compared with those of the younger boys (5-9 years of age). The children were divided into three family size groups (small, up to 4 members; medium, 5-7 members; and large, 8 or more) to investigate the effect of family size on the biochemical data. The children from smaller families showed significantly higher levels of haemoglobin and serum vitamin A compared with the children from large families. For serum protein, copper and zinc, there was no statistically significant difference between the children of different family size groups. To analyse the effect of family income, children were divided into three income groups (low, up to taka 2000; medium, taka 2001-4500; and high, 4501 or more). The children from the low family income group had significantly lower serum protein (7.5 g/100 ml) and haemoglobin (13.4 g/100 ml) levels compared with those of the children from the high family income group (for protein, 7.7 g/100 ml and haemoglobin, 14.1 g/100 ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623852 TI - Observations on the development of stunting in children of the Khon Kaen region of Thailand. AB - A cohort of children in North-East Thailand was followed from birth to 2 years of age in an attempt to throw light on factors determining the development of stunting in linear growth. By 2 years the group as a whole had an average deficit in height of nearly -2 standard deviations. Those index children whose sibs were stunted had larger deficits than those with normal sibs. Their mothers were also shorter and lighter. These findings suggest that it is possible to think in terms of stunted families. No differences were identified in socio-economic factors and the prevalence of infection was in general low. Dietary intakes estimated by 24 hour recall, supplemented at 1 and 2 years by 24 h weighing, were satisfactory for most nutrients except iron, calcium and niacin. Intakes of Ca and P were lower in the more stunted children. A number of variables were measured in urine and blood at 1 and 2 years but few relationships could be established with the degree of stunting. Excretions of calcium and phosphorus showed weak negative correlations with height. On average the serum concentration of calcium was satisfactory but that of phosphorus was somewhat low. Concentrations of somatomedin C, thyroxin and vitamin D were within reported normal ranges, with no relation to the degree of stunting. From a comparison of the linear growth of these children with the results of other reports from Thailand it is suggested that environmental factors have produced stunting in the cohort as a whole, but the cohort is essentially homogeneous, showing within it a normal range of genetic variation. If that is so, major differences in intake or biochemistry between the taller and shorter children would not be expected. The problem remains of why the group as a whole is stunted. This is the first systematic attempt to assess biochemical factors that may be related to stunting in Third World children; these results are essentially negative, although there are hints that point at a possible deficiency of calcium. PMID- 1623853 TI - Weight-for-height in children aged 4-12 years. A new index compared to the normalized body mass index. AB - Data from the 1990 survey of the National Study of Health and Growth, comprising 3357 white English boys and 3050 white English girls, were used to construct and evaluate a new index of weight-for-height. Prediction of triceps + subscapular skinfold thickness, using half of the data, led to the index (weight 9)/height3.7, where weight was in kilograms, height in metres. Using the second half of the data the index was shown to have almost as good a correlation with normalized (triceps + subscapular skinfold) as the body mass index (BMI) in children aged 4-12 years. The new weight-for-height index had stable variance from age 4 to 12 years after simple log transformation, unlike the BMI which required transformation via three age-related parameters prior to analysis or centile calculation. Neither index was a good proxy for skinfold measurements for comparison of ethnic groups. From data from inner city areas surveyed in 1989 children of Indian subcontinent origin had substantially lower weight-for-height, but only Gujarati children were thinner than white children, whereas Afro Caribbean children were slightly heavier for their height, but thinner. Centiles of weight-for-height, and of BMI by age, for ages 4-12 years, were calculated for white English boys and white English girls. PMID- 1623854 TI - Energy and macronutrient intake in relation to cancer incidence among Swedish women. AB - Two dietary reporting methods were used to examine associations between macronutrient intake and subsequent cancer incidence in a cohort of Swedish women born between 1908 and 1930. 1361 subjects gave 23-h dietary recalls at their baseline examinations in 1968-1969, and 412 of them also provided detailed dietary histories. The cohort was followed up 19 years later by means of linkages with the National Cancer and Death Registries. Both dietary methods indicated that subjects who were ranked in the highest tertile of energy intake, relative to the lowest, were at significantly greater risk of developing cancer (all site). Relative risks across energy intake tertiles were 1, 1.15 and 2.04, respectively, using the dietary history method and 1, 1.02 and 1.55 using the 24 h recall data. Examination of specific macronutrient energy sources indicated that dietary fat and carbohydrate are likely to have made the largest contribution to this association. However, after adjustment for total energy, none of the individual macronutrients was significantly associated with all-site cancer, by either dietary reporting method. When expressed as a percentage of total energy, low protein density of the diet was associated with increased cancer risk, by both dietary methods. However, this appeared to be a function of high energy intake rather than low protein intake. Simultaneous statistical adjustment for seven potential confounders of the association between energy intake and cancer was performed using both the 24-h recall and the dietary history data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623855 TI - Blunted seasonal variation in serum 25-hydroxy vitamin D and increased risk of osteomalacia in vegetarian London Asians. AB - Serum 25-hydroxy vitamin D levels were measured in 297 adult Asians and 68 white subjects at different times of year and seasonal variation compared between subjects grouped according to ethnic origin, religion and dietary habit. A sub group of Asians with symptoms and biochemical changes suggestive of osteomalacia underwent bone biopsy, and static bone histomorphometry was performed. Histological osteomalacia was detected in 15 Asians and borderline changes in 13. The majority of these cases were among vegetarian Hindus. Significant seasonal variation in 25-hydroxy vitamin D was observed in all groups, but with lower peak and trough levels among Asians, and especially the Hindus and vegetarian Asians. Summer rises in 25-hydroxy vitamin D levels were blunted among Hindus and vegetarian Asians, compared to whites, Muslims and non-vegetarian Asians. Vegetarian Asians had significantly lower serum calcium and higher PTH levels than non-vegetarians, but multivariate analysis indicated that this was an effect of osteomalacia, not vegetarianism. We conclude that solar exposure has a significant effect on vitamin D status in Asians resident in London. Non vegetarian Asians have similar rise and peak levels to whites, but those taking a vegetarian diet (in particular, Hindus) have an impaired seasonal rise in 25 hydroxy vitamin D levels, and are at particular risk of metabolic bone disease. This effect did not appear to be mediated through secondary hyperparathyroidism consequent on a vegetarian diet. PMID- 1623856 TI - Nutritional profiles of chronic alcoholics. AB - An epidemiological study of 58 variables from 300 chronic alcoholic and normal subjects was carried out in the Cardiology, Gastroenterology, Neurology, Psychiatry and Alcohology Departments in order to research, within this chronic alcoholic population, a correlation between diet, alcohol intake, tobacco use and the various alcohol-related diseases. A standardized questionnaire (previously tested) was used to relate dietary intakes (proteins, fats, carbohydrates, water and energy) to drinking and smoking habits. Discriminant analyses were used as appropriate. The alcoholic population is made up of subjects with strong oral intake behaviour and can be classified in relation to their alcohol-related diseases. The alcoholics with cardiovascular and digestive diseases have the two (1st and 2nd) richest diets, respectively, consisting mainly of saturated fats and animal proteins, together with the lowest daily alcohol intake, the highest recorded total quantities of alcohol intake and the longest period of alcohol abuse before alcohol-related disease diagnosis. The 4th and 5th places can be reserved for the alcoholics with neurological and psychiatric diseases with opposite eating and drinking behaviours, i.e. with the poorest diet (less in terms of proteins and fats, although more than the normal population), the highest daily alcohol intake, the lowest quantities of total alcohol intake and the shortest time of alcohol abuse before disease diagnosis. The alcoholic population with subjects free of alcohol-related disease including mixed subjects, who either had not yet started or will never present any alcohol related disease, occupy the intermediate place (3rd) in this classification. PMID- 1623857 TI - Interleukin-1 in alcoholic cirrhosis of the liver: the influence of nutrition. AB - Interleukin-1 (IL-1) is a cytokine produced by the macrophage-monocyte system that has important effects on immunological responses and inflammatory reactions. Several clinical studies have shown that severe protein energy malnutrition adversely effects cell-mediated immune responses and the functional state of macrophages. The objective of this study was to analyse IL-1 production by adherent cells stimulated in vitro with lipopolysaccharide B (LPS) from patients with alcoholic cirrhosis of the liver and its possible relationship with nutritional states. Forty-five patients with alcoholic cirrhosis and 28 healthy donors were investigated. A combined index of nine anthropometric and biochemical parameters was used to evaluate nutritional status of cirrhotic patients, allowing a distinction to be made between those patients with acceptable nutrition (group I: 40%), those with slight malnutrition (group II: 37.7%), and those with severe malnutrition (group III: 22.3%). IL-1 activity was significantly lower in the cirrhosis patients than in the controls (P less than 0.001). This activity also was significantly lower in samples obtained from cirrhotics with severe malnutrition than in those with acceptable nutrition (P less than 0.05); the combined index and the sole anthropometric index gave the same results, suggesting that malnutrition may play a role in the immunoregulatory disturbances in the pathogenesis of alcoholic liver disease. PMID- 1623858 TI - Cardiovascular mortality and morbidity in seven counties in Sweden in relation to water hardness and geological settings. The project: myocardial infarction in mid Sweden. AB - An east-west regional gradient in cardiovascular mortality was found within seven counties in mid-Sweden during the years 1969-1983. The mortality differences were of considerable magnitude for ischaemic heart disease (IHD) as well as for stroke. In previous reports, in which the distribution of risk factors among middle-aged men was presented, the moderate variation among the communities could not explain the mortality variation. Water hardness has previously been reported to be inversely related to cardiovascular mortality in several countries. In this paper, water samples from all 76 communities in seven counties were analysed in relation to mortality rates from IHD and stroke for men and women. Water hardness (Ca+Mg and other minor constituents), and the sulphate and bicarbonate concentrations of the drinking water were inversely related to IHD as well as stroke mortality. The water factors were also inversely related to non-fatal IHD even when account was taken of the age variation and the traditional risk factors as measured by a postal questionnaire. Variation of the water factors accounted for 41% of the variation in IHD mortality rate and 14% of the variation in stroke mortality rate over the 76 communities. PMID- 1623859 TI - The Tromso study: the prevalence of exercise-induced silent myocardial ischaemia and relation to risk factors for coronary heart disease in an apparently healthy population. AB - A random population sample of 294 men and 312 women aged 20-64 years, all apparently healthy, were examined following a screening to determine the prevalence of silent ischaemia and its relations to coronary risk factors. Based on exercise testing, the prevalence of silent ischaemia was 2.5% in men and 3.4% in women. In men, silent ischaemia was positively related to systolic blood pressure (P less than 0.001). The other risk factors did not show any significant associations with silent ischaemia. However, the men with silent ischaemia had a higher coronary heart disease risk score, and a tendency towards more symptoms and signs suggesting a poorer health status than the other men and the women. In the 21 men classified as 'hypertensives', silent ischaemia was more common than in the normotensive men (14% versus 2%, P less than 0.001). No such difference was observed in women. In conclusion, silent ischaemia may be a sign of hypertension and a generally increased risk of coronary heart disease in men, but probably not in the majority of women. This further supports that exercise electrocardiography has no role in screening asymptomatic persons for coronary heart disease, probably with the exception of middle-aged men with an increased risk. PMID- 1623860 TI - Left ventricular diastolic and systolic function in normotensive obese subjects: influence of degree and duration of obesity. AB - The present study was carried out to evaluate systolic and diastolic parameters in overweight and moderately obese, but otherwise healthy subjects, and in a lean control group, to determine whether degree and duration of obesity can influence left ventricular function. A total of 27 subjects, 17 overweight or with moderate obesity and 10 lean, healthy subjects were included. Patients were divided into three groups according to their body mass index (BMI) and to Garrow's criteria as follows: lean control group (BMI less than 25 kg.m-2); overweight subjects (BMI from 25 to 30 kg.m-2); moderately obese subjects (BMI greater than 30 less than 40 kg.m-2). Systolic and diastolic parameters were measured using blood pool gated radionuclide angiography. Left ventricular (LV) ejection fraction (EF), peak ejection rate (PER), time to PER (tPER), peak filling rate (PFR) and time to PFR (tPFR) were evaluated. PER and PFR values were normalized for end-diastolic volume (EDV). EF and PFR were significantly lower (P less than 0.05) both in moderately obese and in overweight subjects and tPFR was significantly (P less than 0.05) prolonged in both groups in comparison to lean controls. Only in moderately obese subjects was PER significantly (P less than 0.05) decreased and tPER significantly (P less than 0.05) prolonged in comparison to lean controls. As compared to overweight individuals, moderately obese subjects were characterized by a significant decrease (P less than 0.05) in LVEF and PER and by a significant increase (P less than 0.05) in tPER, without relevant change in PFR and in tPFR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623861 TI - Acute effects of cigarette smoking on left ventricular diastolic function. AB - Cigarette smoking increases coronary resistance in patients with coronary artery disease, causing profound disturbances in myocardial perfusion. The acute effects of smoking a single cigarette on left ventricular diastolic function were studied in 20 smokers with typical angina pectoris and angiographically documented coronary artery disease. Twenty healthy smokers served as a control group. We used simultaneous M-mode echocardiography of the mitral and aortic valves to measure isovolumic relaxation time, and pulsed Doppler echocardiography of transmitral blood flow was recorded to evaluate left ventricular filling before and immediately after smoking. In the patients with coronary artery disease, systemic blood pressure and heart rate significantly increased after smoking. The isovolumic relaxation time, the deceleration time as well as peak A velocity remained unchanged. The peak E velocity decreased by 0.06 m.s-1 (P = 0.02) and the peak E/A velocity ratio by 0.17 m.s-1 (P = 0.01). There were no significant changes in left ventricular diastolic function indexes in the controls. These results indicate that in patients with coronary artery disease, each cigarette provokes disturbances of left ventricular diastolic function. PMID- 1623862 TI - Abnormal diastolic filling patterns in chronic heart failure--relationship to exercise capacity. AB - Abnormal patterns of diastolic ventricular filling are well recognized in chronic heart failure, but their relationship to the severity of heart failure is not known. The present study evaluates the relationship of diastolic filling indices to the severity of heart failure and to exercise capacity. In 40 patients with chronic heart failure secondary to ischaemic left ventricular impairment, exercise capacity was measured as peak oxygen consumption (VO2max) by progressive treadmill exercise. Left ventricular function was assessed by M-mode and Doppler echocardiographic indices. Peak aortic velocity correlated weakly with VO2max (R = +0.38, P less than 0.05). VO2max did not correlate with other systolic indices, including mean aortic acceleration, time to peak velocity, or isovolumic contraction time. VO2max correlated with the mitral inflow E/A ratio (R = -0.57, P less than 0.005) and with the Doppler estimate of isovolumic relaxation time (R = -0.48, P less than 0.01). Two distinct patterns of diastolic filling were observed: subjects with mild-to-moderate heart failure (NYHA grade II, VO2max 15 20 ml.kg-1.min-1) had abnormally low E/A ratios and long isovolumic relaxation times, whereas those with severe heart failure (NYHA grade III-IV, VO2max less than 12 ml.kg-1.min-1) had abnormally high E/A ratios and short isovolumic relaxation times. Different patterns of abnormal diastolic filling with different degrees of severity of heart failure may explain some of the previous controversy as to the prevalence of abnormal diastolic function in chronic heart failure. Exercise capacity in chronic heart failure appears more closely related to abnormalities of diastolic filling pattern than to indices of systolic function. PMID- 1623863 TI - Ischaemic heart disease, skeletal muscle fibres and exercise capacity. AB - Twenty-eight male patients with ischaemic heart disease (IHD) performed OBLA (onset of blood lactate accumulation) exercise stress tests and had muscle biopsies taken from their vastus lateralis muscle the day before coronary bypass grafting. All 28 patients showed the same exercise performance pattern as compared to healthy sedentary, age-matched, controls: a low exercise intensity eliciting a blood lactate concentration of 2.0 mmol x l-1 (WOBLA), WOBLA corresponded to a high fraction (% WOBLA) of WSL (symptom limited or 'maximal' capacity), and a low peak blood lactate concentration. The high % WOBLA and low peak blood lactate indicated a reduced glycogenolytic capacity ('anaerobic' performance). Muscle fibre composition disclosed a high mean value of fast twitch (FT), type II or 'white' muscle fibres, as compared to sedentary healthy controls. This indicated that this patient group constituted an extreme subgroup of the age-matched population. The distorted muscle fibre composition in IHD could reflect both heredity as well as adaptation to physical inactivity, degenerative cytosolic properties, etc. Muscle and blood contents of a mitochondrial electron translocator and nonspecific radical scavenger, ubiquinone or coenzyme Q10(CoQ10), were low, which coincided with an elevated frequency of the fibre subgroup FT(c). The presence of the FT(c) fibre type is assumed to reflect histological trauma. PMID- 1623864 TI - Electropharmacological testing by transoesophageal atrial pacing in inducible supraventricular tachyarrhythmias. A good approach for selection of long-term anti-arrhythmic therapy. AB - Sixty-eight patients with disabling episodes of inducible supraventricular tachyarrhythmia were tested electropharmacologically by transoesophageal atrial pacing. Using this technique we induced clinical arrhythmia in 67 (98.5%); 26 (38.8%) had a reciprocating tachycardia due to AV node reentry and 41 (61.2%) a by-pass tract. In the latter we induced a reciprocating tachycardia in 12 (29.3%), atrial fibrillation in 25 (36.5%) and both in 14 (34.2%). We then performed an anti-arrhythmic drug test and a transoesophageal reevaluation either after acute intravenous drug administration or during oral steady state. Altogether we tested 111 drugs or a combination of drugs before the results were considered positive; all patients tolerated the procedure well and were discharged with the drug or combination of drugs judged effective. At follow-up of 16.6 +/- 8.5 months, 42 patients (62.7%) were symptom-free, 17 (25.3%) had minor and non-disabling relapses, six (9%) stopped the drug because of inefficacy (1-1.5%) or side effects (5-7.5%); two (3%) dropped out. We conclude that electropharmacological testing with transoesophageal pacing constitutes a very good approach for inducible supraventricular tachyarrhythmias: it permits selection of optimal long-term anti-arrhythmic treatment and is well tolerated, only slightly invasive and without adverse effects. PMID- 1623865 TI - Thrombolysis and coronary occlusion: effects upon the non-infarct zone. AB - Regional wall motion was examined by angiography after 3 weeks in 154 patients taking part in the Thrombolysis in Coronary Occlusion (TICO) Trial. Coronary patency rate was greater after administration of recombinant tissue plasminogen activator, (rt-PA 62/77pts 81%) than after a placebo (P 49/77pts 64% P = 0.02), particularly for the left anterior descending artery compared with the right coronary artery (LAD 27/28 96% vs RCA 28/40 70% P = 0.006). Left ventricular ejection fraction (LVEF) was preserved after rt-PA (rt-PA 59 +/- 14% vs P 53 +/- 15% P = 0.01), predominantly because of more effective non-infarct zone contraction (rt-PA 0.52 +/- 1.16 SD/cord vs P 1.01 +/- 1.07 SD/cord P = 0.008). Infarct zone scores differed little (rt-PA 2.88 +/- 0.95 SD/cord vs P 3.16 +/- 1.11 SD/cord P = 0.09). Left ventricular ejection fraction and non-infarct zone function were best preserved after rt-PA compared with the placebo, particularly in patients with single vessel disease and in patients in whom the infarct related artery was the left anterior descending vessel. PMID- 1623866 TI - Drug-testing in patients with pulmonary hypertension of unknown cause. AB - The acute haemodynamic effects of seven different drugs were serially evaluated in eight patients suffering from pulmonary hypertension of unknown cause. The following drugs were tested in randomized order: nifedipine, amrinone, isoproterenol, captopril, prostacyclin, dihydralazine and nitroglycerin. Only a reduction in pulmonary vascular resistance (PVR) of more than 30% of baseline was considered a satisfactory response. Overall, the decrease in PVR ranged from 9 +/ 12% (nitroglycerin) to 38 +/- 23% (prostacyclin). However, marked inter- and intra-individual variability in the efficacy of all drugs was observed, making cross reactivity totally unpredictable. The number of responders for each drug varied between five (prostacyclin) and zero (dihydralazine, nitroglycerin). Conversely, a maximum of three drugs was capable of eliciting a response in an individual patient, with only two out of eight patients being total non responders. A reduction in PVR of more than 30% (n = 16) was associated with a significant decrease in mean pulmonary artery pressure (49.1 +/- 8.2 versus 39.4 +/- 6.4 mmHg) and a significant increase in cardiac index (2.5 +/- 0.6 versus 3.4 +/- 0.8l.min-1.m-2). Overall, none of the drugs tested proved to be clearly superior. However, because of marked inter- and intra-individual variability, the therapeutic approach must be based on trial and error and the evaluation of all drugs is indicated if one fails. PMID- 1623867 TI - Comparative long-term results of coronary angioplasty in single and multivessel disease. AB - The comparative long-term clinical results of coronary angioplasty in 448 patients with single-vessel and 451 patients with multivessel disease are reported. Clinical status was determined at census for 898 patients (99.9%). Actuarial survival at 5 years was 92.7% for single-vessel and 85.6% for multivessel disease patients (relative risk 2.1). Patients with multivessel disease had higher rates of cardiac death and non-fatal myocardial infarction (relative risk 1.8), and coronary artery bypass surgery (relative risk 2.5) than patients with single-vessel disease. At follow-up 72.6% of single-vessel and 61.3% of multivessel disease patients had no angina and 43.3% and 35.8%, respectively, were taking no regular anti-anginal medication. Treatment by coronary angioplasty is associated with a good long-term prognosis, but survival and event-free survival rates are lower in patients with multivessel disease than in patients with single-vessel disease, even after correction for differences in other baseline characteristics. PMID- 1623868 TI - Logistical problems in prehospital thrombolysis. AB - In this study we compared efficacy and safety of prehospital with in-hospital thrombolytic treatment with anistreplase in patients with acute myocardial infarction (AMI). Three-hundred and fifty patients with chest pain were screened for eligibility by the municipal ambulance staff and/or the general practitioner. Patients were included in the absence of contraindications and if the telephone transmitted ECG showed AMI. In a 6 month period 16 patients (5%) were eligible, but only seven (2%) were randomized. Age over 70 years, duration of chest pain for longer than 4 h and logistic problems were the major factors responsible for the low inclusion rate. The mean time spent at home with and without the ECG procedure was 38 +/- 14 and 14 +/- 8 min, respectively (P less than 0.001). These results demonstrate that in a medium sized town prehospital delivery of intravenous thrombolytic therapy by paramedics and/or the general practitioner is not feasible, leads to unnecessary time delay and may therefore yield no clinical benefits. PMID- 1623869 TI - Oxygen consumption during corridor walk testing in chronic cardiac failure. AB - We have examined the use of a 6-min corridor walk test in the assessment of functional capacity in 16 patients with chronic cardiac failure. VO2 was determined concurrently by a portable 'Oxylog'. Three tests were performed sequentially, and although there was a significant increase in distance walked and highest VO2 achieved between the first and second tests, good reproducibility was attained between the second and third tests. Both walk test variables correlated well with previously determined peak achieved VO2, and NYHA classes were separated adequately. Corridor walk testing, with or without measurement of VO2 should be a useful adjunct to maximal exercise testing in interventional studies. PMID- 1623870 TI - Comparison of thallium myocardial scintigraphy after exercise and transoesophageal atrial pacing in the diagnosis of coronary artery disease. AB - Forty-nine patients admitted for assessment of chest pain underwent coronary angiography, planar Thallium 201 myocardial scintigraphy after submaximal exercise (TE) and transoesophageal atrial pacing (TAP). Early hypofixation with redistribution after 4 h indicated ischaemia. The criterion for a myocardial infarction (MI) was a fixed perfusion defect. Coronary angiography was carried out in all patients. Sixteen patients (group 1) had no MI and over 50% narrowing of at least one main coronary vessel. Ischaemia was noted in 10 of the 16 patients during exercise, and in 14 of the 16 patients during atrial pacing. The sensitivity for the prediction of coronary stenosis was 62% for TE and 87% for TAP. Nineteen patients (group 2) had had a previous MI. Reversible ischaemia was noted in 10 of the 19 patients during exercise, and in 11 of the 19 patients during TAP. Four of 14 patients with normal coronary arteries (group 3) had a reversible ischaemia with TE, and three of these same patients developed a positive scan with TAP. The respective specificities were 71% and 78%. Comparison of segmental hypoperfusion after TE and TAP gave identical results in 72 of the 80 segments studied in group I (90%), and in 88 of the 95 segments studied in group 2 (92%). The localizing value of TAP was good in left anterior descending (12 out of 18) and right coronary disease (16 out of 19), but poor in left circumflex stenosis (3 out of 9) misclassified as right coronary disease in four patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623871 TI - Further evidence supporting the concept of T-wave memory: observation in patients having undergone high-energy direct current catheter ablation of the Wolff Parkinson-White syndrome. AB - Following successful high-energy direct current catheter ablation of posterior septal accessory pathways, serial T-wave changes were observed in seven patients with Wolff-Parkinson-White syndrome, but not in two patients with a concealed accessory bypass pathway. Following catheter ablation in the patients with Wolff Parkinson-White syndrome, the previously upright T-waves in the inferior electrocardiographic leads became inferiorly directed. Serial electrocardiograms following catheter ablation revealed slow regression of these T-wave changes over time. In contrast, in the two patients in whom a concealed accessory pathway was present, the T-waves prior to and following the procedure were upright. In these two patients, serial electrocardiograms showed no evolution of the T-wave vector over the same time period. Although a small rise in myocardial CK enzymes was observed, ischaemic injury in the area of catheter ablation could not be documented by post-procedure echocardiography, tomographic thallium scintigraphy, technetium pyrophosphate scintigraphy or coronary angiography with left ventriculography. We conclude that the observed T-wave changes in the patients with Wolff-Parkinson-White syndrome may be a result of the change in depolarization sequence resulting from loss of pre-excitation, and that the time dependent nature of these T-wave changes is consistent with the concept of T-wave 'memory'. PMID- 1623872 TI - Flecainide-related alterations in the signal-averaged electrocardiogram: similarity between patients with or without ventricular tachycardia. AB - The signal-averaged electrocardiogram (SAECG) identifies patients at risk of sustained ventricular tachycardia (VT), but the influence of anti-arrhythmic agents on the SAECG is not yet established. We have evaluated the effects of flecainide on the SAECG (XYZ leads, high-pass filters 25 Hz and 40 Hz, noise level 0.2 microV-0.4 microV, Model 1200 EPX, ART) in 25 patients: 15 (VT group) had documented sustained VT (nine post-MI, two dilated cardiomyopathy, four normal hearts) and 10 (control group) had supraventricular arrhythmias and structurally normal hearts. The SAECG was recorded in all patients prior to, and 5 min following a flecainide infusion (2 mg.kg-1 over 10 min). Before flecainide administration an abnormal SAECG was recorded in six patients from the VT group and in no control patient. Following flecainide, 13 patients from the VT group and eight control subjects demonstrated abnormal SAECG. Flecainide produced similar significant percentage changes in all SAECG indices in both the VT and control groups: total QRS duration was prolonged by 26.0 +/- 10.4% vs 26.7 +/- 15.7%, late potential duration under 40 microV was prolonged by 55.5 +/- 62.0% vs 106.1 +/- 61.4%, and the root mean square voltage of the last 40 ms of the QRS was reduced by 42.1 +/- 34.9% vs 55.3 +/- 24.4%, respectively. We conclude that flecainide significantly changes the SAECG parameters in patients with and without a history of VT, irrespective of the underlying disease. PMID- 1623873 TI - Absence of pre-dose rebound phenomena with once daily 5-ISMN in a controlled release formulation. AB - To avoid the development of nitrate tolerance secondary to relatively constant elevated plasma nitrate concentrations, intermittent nitrate dosing has been advocated. However, a nitrate-free interval may induce a rebound increase in myocardial ischaemia, and thus increase anginal symptoms during the latter portion of the dosing interval. This was suggested by the results of recent studies in which nitroglycerin patches were administered intermittently with a 12 h nitrate-free interval. The present investigation was carried out to determine whether a controlled-release formulation of 60 mg isosorbide-5-mononitrate (5 ISMN) would produce such a rebound phenomenon. Seventy-nine patients, who had participated in four crossover, placebo-controlled studies in which the treatment arms lasted for between 1 and 2 weeks, were reviewed. These studies had assessed the efficacy of this nitrate preparation by exercise testing and each had included exercise testing at the end of each treatment phase, 24 h after the last medication had been administered. There were no differences noted in the time to onset of angina, the time to onset of 1 mm ST segment depression or the total exercise duration between the two treatment phases, indicating an absence of rebound phenomena at the end of the dosing interval. The reason for the absence of a detectable pre-dose rebound is unclear, but the plasma concentration profile of 5-ISMN produced by the presently used preparation, resulting in a nitrate-low instead of nitrate-free interval, may have contributed. PMID- 1623874 TI - Efficacy and safety of APSAC in the treatment of acute myocardial infarction. AB - A prospective, open, multicentre post-marketing surveillance on the efficacy and safety of intravenous APSAC in the treatment of acute myocardial infarction was performed in 2436 patients. Reperfusion suggested by non-invasive parameters was achieved in 77.3% of patients. In-hospital mortality was low (7.1%). After exclusion from analysis of patients greater than 70 years of age and those reported to be in cardiogenic shock, mortality rate was 2.9%. More importantly, non-invasive evidence for successful thrombolysis resulted in a significantly lower mortality (3.3%) compared with patients without evidence of successful reperfusion (17.2%). The incidence of serious adverse events was low (132 in 2436 patients, 8/2436 = 0.3% fatal). The data from this post-marketing surveillance conducted under every-day clinical conditions confirm the efficacy and safety of APSAC as a thrombolytic agent in acute myocardial infarction, as demonstrated previously in controlled clinical trials. PMID- 1623875 TI - Paradoxical vasoconstriction as result of acetylcholine and serotonin in diseased human coronary arteries. AB - In experimental atherosclerosis, impairment of endothelium-dependent vasodilation results in an unmasking of potent vasoconstrictor responses to serotonin, a substance released by aggregating platelets. To determine whether similar changes occur in diseased human coronary arteries, the responses to selective intracoronary infusions of acetylcholine and serotonin (both endothelium dependent vasodilators) and to isosorbide dinitrate (a dilator directly acting on the smooth muscle) were assessed by quantitative coronary arteriography in 16 patients with angiographically normal coronary arteries, in 10 patients with minimal (less than 30% narrowing) and in five patients with more advanced (greater than 50% narrowing) coronary atherosclerosis. Acetylcholine induced constriction in diseased coronary arteries, but in patients with normal coronary arteriograms, it caused dilatation in seven patients (smooth dilators) and constriction in nine patients (smooth constrictors). In the smooth dilators, however, serotonin evoked no significant changes (+1.4 +/- 4.1%), whereas in the smooth constrictors and in patients with diseased coronary arteries, serotonin caused dose-dependent constriction. The vasoconstrictor responses to serotonin were similar in patients with minimal (-26.5 +/- 4.7%) and more advanced atherosclerosis (-30.9 +/- 5.3%). In one patient with coronary artery disease, serotonin caused a temporary coronary occlusion. All other patients dilated in response to isosorbide dinitrate. The vasomotor responses to acetylcholine and to serotonin were thus shown to be completely in parallel. CONCLUSION: impairment of endothelium-dependent vasodilation unmasks potent vasoconstrictor responses to serotonin both in early and advanced coronary atherosclerosis. These changes may play an important role in the pathogenesis of a dynamic coronary artery stenosis. PMID- 1623876 TI - Fatal haemostatic complications due to thrombolytic therapy in patients falsely diagnosed as acute myocardial infarction. AB - This report describes the fate of two young men wrongly treated with thrombolysis for suspected myocardial infarction. Both had electrocardiographic changes upon admission. Correct diagnosis of aortic dissection and haemorrhagic pericarditis was obtained within a few hours, but due to the prolonged disturbance of haemostasis, appropriate therapy could not be instituted, and outcome was fatal for both patients. These cases underline the importance of rigid ST criteria, and procedures for neutralization of thrombolysis are proposed. PMID- 1623877 TI - Myocardial dissection following successful chemical ablation of ventricular tachycardia. AB - We describe a case of fatal myocardial rupture and tamponade following a successful transcoronary chemical ablation of incessant ventricular tachycardia. Pathological examination showed a subepicardial dissection of the heart at the ablation site with fibrous and fatty degeneration of the myocardium. The present report calls for caution, underlying a possible lethal complication of ethanol ablation which has not been described before. PMID- 1623878 TI - Emergency mitral valve replacement immediately following caesarean section. AB - Cardiopulmonary bypass immediately post-partum could carry the risk of severe uterine bleeding. We report the case of a woman who successfully underwent emergency replacement of a thrombosed mitral prosthesis immediately after Caesarean section. PMID- 1623879 TI - Total occlusion of the left main coronary artery and normal LV function despite critical narrowing of the right coronary artery. PMID- 1623880 TI - Development of nitrate tolerance and usefulness of pulse therapy in a patient with vasospastic angina. AB - In a 58-year-old man with vasospastic angina, we investigated the relationship between the antianginal effects of isosorbide dinitrate (ISDN) and plasma ISDN concentration. Despite adequate plasma ISDN levels, sustained therapy using ISDN tapes and oral ISDN (transcutaneously 160 mg and orally 100 mg ISDN day-1) failed to exhibit antianginal effects. However, pulse therapy using sublingual short acting ISDN prevented anginal episodes, although the plasma ISDN levels were less than those of sustained therapy. Nitrate tolerance of the antianginal effects was avoided by creating an abrupt plasma ISDN concentration gradient using sublingual ISDN. PMID- 1623881 TI - Fatal anaphylactoid response to protamine after percutaneous transluminal coronary angioplasty. AB - A generalized skin erythema and severe hypotension developed following administration of protamine for the reversal of heparin anticoagulation after an unsuccessful attempt at percutaneous transluminal angioplasty in a patient who had never been exposed to protamines before. Evidence of classical pathway complement activation was present indicating that this reaction could have been triggered by a non-immunological mechanism. The patient could not adequately be resuscitated because of the presence of severe coronary artery disease. PMID- 1623882 TI - Pleuritis-pericarditis--an unusual initial manifestation of mixed connective tissue disease. AB - Cardiac involvement has been reported in mixed connective tissue disease (MCTD). We describe a 16-year-old girl in whom pleuritis and pericarditis occurred as the initial clinical manifestations of MCTD. Although pleuritis and pericarditis form a common clinical entity in MCTD, it is rarely seen as an initial manifestation. If MCTD is suspected, the diagnosis can be made by the clinical findings and the occurrence of a high titre of antibody against ribonuclease-sensitive ribonucleoprotein (RNP). This report emphasizes the importance of screening for connective tissue disease in patients with pericarditis/pleuritis. PMID- 1623883 TI - From Harvard to Minnesota: keys to our history. PMID- 1623884 TI - Sport and the mass media. PMID- 1623885 TI - Regulation of hormonal and metabolic responses during exercise in humans. PMID- 1623886 TI - Human energy expenditure from Australopithecus afarensis to the 4-minute mile: exemplars and case studies. PMID- 1623887 TI - Anxiety and sport performance. AB - From the findings summarized in this review, it appears that there is little evidence in support of the inverted-U hypothesis. Available research indicates that there is considerable variability in the optimal precompetition anxiety responses among athletes, which does not conform to the inverted-U hypothesis. Many athletes appear to perform best when experiencing high levels of anxiety and interventions that act to produce quiescence may actually worsen the performance of this group. These findings indicate that there is a need to shift the research paradigm away from theories of anxiety and performance based on task characteristics or group effects and, instead, employ theoretical models that account for individual differences. Hanin's [39, 40] ZOF theory appears to be a good candidate for furthering our knowledge in this area. It was developed on the basis of research with athletes and it explicitly incorporates the concept of individual differences in the anxiety-performance relationship. Most important, because an individual's optimal range of anxiety is precisely defined, the validity of ZOF theory can be directly examined through hypothesis testing, whereas it has been argued that the inverted-U hypothesis is effectively shielded against falsification [84]. Although the findings of ZOF theory indicate that a significant percentage of athletes perform best at high levels of anxiety, Hanin's translated writings do not provide an explanation of why this is so. Further research is clearly indicated, but one explanation for this finding may involve how the athlete interprets or conceptualizes anxiety. For example, Mahoney and Avener [64] found that, although the absolute level of precompetition anxiety was similar between successful and unsuccessful Olympic gymnasts, there were differences in the way the athletes conceptualized the anxiety they were experiencing. The better performers viewed their anxiety as desirable, whereas anxiety was associated with self-doubts and catastrophizing in the unsuccessful gymnasts. Similar differences have been observed in the test anxiety literature where it has been found that poorer test takers perceive their anxiety to be more threatening and debilitating than do better performers [45]. Furthermore, temporal differences in the patterning of anxiety [64], fear responses, or cardiorespiratory measures [28] have been found between successful and unsuccessful performers; this may reflect a difference in the ability to regulate anxiety. It may also be the case that performance is not so much affected by the absolute level of precompetition anxiety as the consistency in the anxiety level across competitions. Athletes may also develop coping strategies that exploit consistent changes in attentional focus that result from elevated anxiety.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1623888 TI - Genetics of aerobic and anaerobic performances. PMID- 1623889 TI - Oxygen transport during exercise at altitude and the lactate paradox: lessons from Operation Everest II and Pikes Peak. AB - It seems unlikely that oxygen-limited metabolism explains the increased lactate concentrations in blood or muscle during exercise at high altitude compared with sea level values because: 1. Even marked hypoxia equivalent to that at the summit of Mt. Everest may not be sufficiently severe to impair function or to impair muscle oxidative metabolism markedly during exercise; 2. At this very high altitude, muscle hypoxemia is probably not the limiting factor for exercise performance; other systems, i.e., the cerebral cortex [24, 33], probably fail before hypoxemia impairs muscle metabolism; 3. The traditional view of oxygen limited aerobic metabolism during exercise at high altitude does not explain a long-standing dilemma in altitude physiology, the lactate paradox (in which blood lactate accumulation during exercise is increased on arrival at high altitude but falls with acclimatization), because the lactate fall is independent of muscle oxygenation; 4. Net lactate release by the leg during exercise is independent of oxygenation; 5. Kinetic studies show that lactate appearance and disappearance are closely linked and both increase with acute altitude exposure and decrease with acclimatization; 6. Lactate appearance rate is strongly correlated with, and may be influenced by, the extent of beta-adrenergic stimulation; 7. The beta adrenergic stimulation may be, in part, determined by the degree of arterial oxygenation. PMID- 1623890 TI - Responses of the cardiac transplant patient to exercise and training. AB - Total denervation persists in the human heart following cardiac transplantation. At rest, there is some increase of heart rate and blood pressure. with a low normal cardiac output. The donor heart remains capable of a satisfactory acute response to exercise, based upon an increase of venous return (acting through the Frank-Starling mechanism) and slower chronotropic and inotropic responses to circulating catecholamines. During submaximal exercise, the stroke volume is greater than normal, but the cardiac output is somewhat reduced, leading to a widening of arteriovenous oxygen difference. Peak heart rate, peak stroke volume, and peak cardiac output are all less than in age-matched normals. Peak power output and peak oxygen intake are also subnormal immediately following cardiac transplantation. The poor ventricular performance reflects, in part, the condition of the transplanted myocardium and, in part, the increased afterloading associated with a loss of lean tissue mass. Although there have, as yet, been no controlled experiments, there is suggestive evidence that an appropriately graded training regimen facilitates restoration of lean tissue and, thus, functional recovery (including the correction of postoperative psychological disturbances). A suitably adapted exercise prescription is thus recommended as a useful component of treatment following cardiac transplantation. There is good evidence that a well-designed training program improves the quality of life for the recipient, although further study is needed to determine the impact of such therapy upon morbidity and mortality. PMID- 1623891 TI - Epidemiology, pathomechanics, and prevention of football-induced cervical spinal cord trauma. PMID- 1623892 TI - Exercise and diabetes mellitus. PMID- 1623893 TI - Exercise and the cutaneous circulation. AB - Our understanding of the control of the cutaneous circulation has increased over the past decade, but is still far from complete. There is a cutaneous vasoconstriction at the beginning of exercise that usually effectively competes with concurrent thermoregulatory drives for vasodilation. This cutaneous vasoconstrictor response, however, requires dynamic activity by a significant muscle mass as small muscle groups or isometric exercise are ineffective or nearly so. Also, exercise causes the threshold internal temperature relative to rest such that SKBF is lower during exercise than in resting conditions for a given thermal stimulus. A further influence by exercise on the cutaneous circulation is to limit the degree of cutaneous vasodilation when heat stress and exercise are combined. These three roles for exercise compete with the thermogenic role that promotes vasodilation. The previously described effects act through the adrenergic vasoconstrictor system and the separate active vasodilator system. The increase in SKBF with heat stress represents the combination of withdrawal of vasoconstrictor activity and elevation of active vasodilator activity. The vasoconstrictor effect of the initiation of exercise is accomplished strictly through enhanced vasoconstrictor activity; vasodilator withdrawal does not participate [72]. However, both the exercise-induced elevation in thermoregulatory threshold for raising SKBF and the limitation to cutaneous vasodilation during exercise are strictly functions of the active vasodilator system [69, 73, 78]. In the first case, active vasodilation is delayed until a higher (relative to rest) level of internal temperature is reached. In the second case, the plateau in SKBF during exercise in the heat is due to a similar plateau in active vasodilator activity. Exercise has also served as a tool for the study of other influences on the cutaneous circulation. The influences of alterations in body fluid volumes, osmolarity, acclimatization, hypertension, time of day, menstrual phase, and others on the control of SKBF have been assessed by using exercise as a calorigenic source. The question as to whether the nonthermoregulatory influences of exercise interact with these other influences to give a modification of the pattern of control different from what might be observed at rest is largely unanswered. Future directions for research are numerous, but several fundamental questions are outstanding. The mechanism of active cutaneous vasodilation has been elusive since its discovery and remains an exceptionally important question. Second, the sensory elements associated with exercise giving rise to the alterations in the pattern of control are unclear. This problem is made challenging by the fact that the efferent control by exercise differs between its initiation and events later in exercise.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1623894 TI - Musculoskeletal adaptations and injuries due to overtraining. AB - Overtraining places a demand on the musculoskeletal system that may lead to damage to the musculoskeletal system, as well as to clinical, functional, and biomechanical adaptations that may be detrimental to sport performance. The types of injuries identified range from overt, which are obvious injuries that will usually prevent athletic performance for some period of time, to the subclinical, which decrease performance, but may be seldom recognized. These injuries apparently may be avoided or lessened in severity by a combination of several methods. A thorough preparticipation evaluation is important to detect subtle adaptations in strength and flexibility that can result from overtraining and may increase the athlete's chances of injury. A good sport-specific conditioning program is necessary to give the athlete a strong musculoskeletal base on which to build athletic skills and to decrease the risk of overtraining adaptation. In many sports, prehabilitation exercises can be performed for those musculoskeletal areas that are under high stress in a particular sport. Also, a maintenance conditioning program that extends through the season may be important to maintain fitness throughout the season. Following proper principles of conditioning, including specificity, recovery, and progression, are important. A complete and accurate diagnosis of the injuries that do occur is necessary so that proper treatment may follow. This can be facilitated by understanding the types of clinical presentations of injuries, and the different anatomical and functional alterations that may be acting to cause or to continue the clinical presentation. By following these general guidelines, safe participation in sporting activities as well as performance will be enhanced. The exact point where "training" becomes "overtraining" is difficult to define, especially prospectively. An exciting area of sports medicine research will be to define the anatomic parameters and exercise doses that will cause overtraining, and to devise fitness examinations and training programs that will allow maximal performance with minimal overload risk. At the present time, retrospective studies do indicate that adaptations occur in muscles, tendons, and bones in response to high training loads, and these particular adaptations are not beneficial to performance and may be associated with increased injury risk. Since the optimal exercise dose is not known, provision for evaluation of these adaptations and prehabilitation of all noninjured areas or proper rehabilitation of all injured areas will best prepare the musculoskeletal system for training. PMID- 1623895 TI - Clinical pharmacology and the provision of drug information. AB - Clinical pharmacologists have a service role in the provision of drug information to individuals both in hospitals and primary health care. We present here a systematic approach in answering questions in a drug information centre (DIC), and describe the working method and the documentation of the work in a question answer (Q/A) data base. Drugline is a full-text data base offering problem oriented drug evaluation comparable to a clinical consultation. The drug information is produced in a non-commercial drug information centre sponsored by the national health care sector and the National Corporation of Swedish Pharmacies, and run jointly by clinical pharmacologists and pharmacists. A minor part of Drugline is available in English for online searching, in parallel with Medline at the database host, the Medical Information Centre at the Karolinska Institute Library and Information Centre, and the users represent mainly medical libraries, hospital pharmacies, university clinics, and the pharmaceutical industry. A network of DICs has been organized in Swedish university hospitals with access to Drugline for searching and the storage of questions and answers. This network has the potential for expansion throughout Europe. It offers the unique possibility of complementing drug product information with problem oriented drug information emerging from cases in the real world of prescribing. PMID- 1623896 TI - Terodiline causes polymorphic ventricular tachycardia due to reduced heart rate and prolongation of QT interval. AB - Recent reports have suggested an association between terodiline hydrochloride and cardiac arrhythmias. We report 4 patients presenting over a six month period who developed polymorphic ventricular tachycardia (polymorphic VT) while receiving treatment with this agent. In each case there was prolongation of QT interval on electrocardiogram (ECG). Two patients had hypokalaemia associated with diuretic therapy. In the 3 cases in which follow-up ECG was available, QT interval returned to normal after discontinuation of terodiline. In order to define the effects of terodiline on corrected QT interval (QTc) and heart rate in the elderly, a prospective study was performed in 8 elderly in-patients treated with terodiline for urinary incontinence. After 7 days treatment with terodiline 12.5 mg twice daily, there was a significant increase in QT by a mean of 29 ms, QTc by 15 ms and a decrease in resting heart rate by a mean of 6.7 beats.min-1. Terodiline increases QTc and reduces resting heart rate in elderly patients. Both these effects may be associated with polymorphic VT, a potentially life threatening arrhythmia. This drug should be avoided in patients with other known risk factors for polymorphic VT, particularly hypokalaemia and cardiac disease. PMID- 1623897 TI - The influence of posture on the response to loop diuretics in patients with chronic cardiac failure is reduced by angiotensin converting enzyme inhibition. AB - The diuretic and natriuretic response to an intravenous dose of frusemide 40 mg was assessed in the erect and supine positions in 10 patients with cardiac failure who were being treated with enalapril 10 mg twice daily in addition to diuretics (Enalapril group) and in 10 patients with cardiac failure taking diuretics alone (Control group). Total 4 h diuresis in the erect position was 728 ml and in the supine position was 824 ml in the patients taking enalapril compared to 655 ml in the erect position and 1166 ml in the supine position in those patients taking diuretics alone. Total 4 h natriuresis in the erect positions was 78 mmol and in the supine position was 85 mmol in patients taking enalapril 10 mg twice daily but in those patients taking diuretics alone total 4 h natriuresis in the erect position was 67 mmol increasing to 120 mmol in the supine position. Measurements of plasma renin activity and plasma angiotensin II concentration confirmed effective converting enzyme inhibition, in the group of patients taking enalapril, but in those patients taking diuretics alone the erect position was associated with an increase in plasma renin activity, and plasma concentrations of angiotensin II and aldosterone. We conclude that the renin angiotensin system is a major factor in mediating the effect of posture on loop diuretic drugs. PMID- 1623898 TI - The effect of quinidine on the analgesic effect of codeine. AB - We have studied the hypoalgesic effect of codeine (100 mg) after blocking the hepatic O-demethylation of codeine to morphine via the sparteine oxygenase (CYP2D6) by quinidine (200 mg). The study was performed in 16 extensive metabolizers of sparteine, using a double-blind, randomized, four-way, cross-over design. The treatments given at 3 h intervals during the four sessions were placebo/placebo, quinidine/placebo, placebo/codeine, and quinidine/codeine. We measured pinprick pain and pain tolerance thresholds to high energy argon laser stimuli before and 1, 2, and 3 h after codeine or placebo. After codeine and placebo, the peak plasma concentration of morphine was 6-62 (median 18) nmol.l-1. When quinidine pre-treatment was given, no morphine could be detected (less than 4 nmol.l-1) after codeine. The pin-prick pain thresholds were significantly increased after placebo/codeine, but not after quinidine/codeine compared with placebo/placebo. Both placebo/codeine and quinidine/codeine increased pain tolerance thresholds significantly. Quinidine/codeine and quinidine/placebo did not differ significantly for either pin-prick or tolerance pain thresholds. These results are compatible with local CYP2D6 mediated formation of morphine in the brain, not being blocked by quinidine. Alternatively, a hypoalgesic effect of quinidine might have confounded the results. PMID- 1623899 TI - Metamizole-furosemide interaction study in healthy volunteers. AB - The pharmacokinetic and pharmacodynamic interactions between metamizole (dipyrone) and furosemide were investigated in 9 of 12 healthy female subjects able to complete the study. They received oral metamizole 3 x 1 g for 3 days or placebo (cross-over) and on the last day of both study periods furosemide 20 mg IV. On the last two days a balanced sodium diet (120 mEq) and on Day 3 an oral water load (600 ml) were given. Metamizole significantly inhibited basal urine flow, whereas the fractional excretion of sodium and chloride and the 12 h-GFR remained unchanged. Metamizole significantly reduced furosemide clearance (175 vs 141 ml.min-1), furosemide-stimulated plasma renin activity (1.42 vs 0.79 ng AI.ml 1.h-1) and the urinary excretion of prostacyclin metabolites and of prostaglandin F2 alpha (by 70-81%). The renal clearance and terminal half-life of furosemide, peak renal chloride and volume excretion were unchanged. Thus, metamizole did not interact with the renal excretion and the diuretic effect of furosemide, although prostaglandin synthesis was significantly reduced. PMID- 1623900 TI - Effect of dexfenfluramine treatment on body weight, blood pressure and noradrenergic activity in obese hypertensive patients. AB - The effect of dexfenfluramine (dF) on body weight, blood pressure and noradrenergic activity were studied in 30 obese hypertensive patients randomly divided into two groups and treated for 3 months either with dF (30 mg daily; 16 subjects) or placebo (Pl; 14 subjects). 11 patients from the dF group and 9 patients given Pl completed the entire experimental protocol, including monthly visits for metabolic and hormonal measurements, as well as a bicycle exercise test with arterial catheterisation for haemodynamic and catecholamine measurements performed before and after 3 months of treatment. A progressive significant decrease in body weight, averaging 6.0 kg after 3 months was observed in the dF-treated group, whereas loss of weight in the placebo group (1.4 kg) was not significant. While blood pressure and noradrenergic activity, assessed as changes in the plasma levels and urinary excretion of norepinephrine, remained unaffected in the Pl group, a significant drop in the supine systolic and diastolic blood pressures, as well as in the resting venous norepinephrine level and in urinary norepinephrine excretion was found after the first month of dF administration. In addition, the exercise-induced rise in systolic and diastolic blood pressure, as well as in arterial plasma norepinephrine and epinephrine concentrations, was significantly reduced after 3 months of dF administration; there were no such changes in the Pl-treated group. The results of the present study indicate that, in addition to the weight-reducing effect of dexfenfluramine, its hypotensive effect may be mediated by a decrease in noradrenergic activity. PMID- 1623901 TI - Rectal bioavailability of 6-mercaptopurine in children with acute lymphoblastic leukaemia: partial avoidance of "first-pass" metabolism. AB - Plasma levels and the area under the plasma concentration-time curve (AUC) values of 6-mercaptopurine (6-MP) were determined in a balanced crossover study of oral (powder) and rectal (macrogol suppository) administration to 5 children with acute lymphoblastic leukaemia (ALL). The AUC (538.6 ng.h.ml-1) after the rectal dose of 30 mg/m2 was approximately 1.5-times of that (365.5 ng.h.ml-1) after the oral dose of 87.5 mg/m2. The coefficients of variation of interindividual variability of the AUCs were 21.5% and 32.3%, respectively. The relative bioavailability of the macrogol suppository compared to the powder was approximately 4.39. These findings indicate that rectal administration of 6-MP could avoid the first-pass effect of this drug in the alimentary canal and/or liver, resulting in a large AUC of 6-MP, and so could reduce interindividual variability in plasma 6-MP concentrations. Rectal administration of 6-MP may be more effective than empirical oral dosing for the treatment of children with ALL, especially for patients with nausea and/or vomiting. PMID- 1623902 TI - In vitro generation of activated natural killer cells and cytotoxic macrophages with lentinan. AB - The in vitro effect of lentinan in inducing activation of killer cells and cytotoxic macrophages has been examined. Human peripheral blood mononuclear cells were cultured with lentinan for 2, 4 and 8 days. After 4 days cytotoxicity was increased 4% by lentinan less than 1,000 ng/ml. After 8 days, it was increased 12% by 25 and 1,000 ng/ml lentinan. The phenotype of the killer cells induced by lentinan was CD2+, CD16+ and CD56+, suggesting that they were natural killer cells. Macrophages separated from the spleens of 6 patients with gastric cancer were cultured with lentinan for 7 days, and their cytotoxicity increased 19%. The optimal concentration of lentinan was from 25 to 100 ng/ml. The findings suggest that the antitumour effect of lentinan is due to the activation of killer cells in vivo, because the optimal concentration of lentinan for the induction of killer cells in vitro was equivalent to the plasma concentration obtained after clinical doses of this agent. PMID- 1623903 TI - The inhibitory effects of a positive inotropic quinolinone derivative, 3,4 dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)- quinolinone (OPC-8212), on bone-marrow progenitor cells and peripheral lymphocytes. AB - 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone (OPC 8212) is a quinolinone derivative with positive inotropic properties. In order to elucidate the effect of OPC-8212 on the haemopoietic system we studied its in vitro effect on bone-marrow progenitor cells (granulocyte/monocyte colony-forming units [CFU-GM] and erythroid burst-forming units [BFU-E]), on the proliferation and secretion of granulocyte/monocyte colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) by peripheral lymphocytes, and on GM-CSF secretion by fibroblasts from healthy individuals. The dose-effect relations of OPC-8212 on CFU-GM proliferation and on lymphocytic GM-CSF secretion showed no effect at very low drug concentrations, with a threshold at the lower end of the therapeutic range and highly significant dose-dependent inhibition at concentrations above that threshold. BFU-E, peripheral lymphocyte proliferation and lymphocytic IFN gamma secretion were depressed, although to a lesser extent, in a linear dose dependent fashion. OPC-8212 did not affect GM-CSF secretion by one strain of fibroblasts but reduced it at higher concentrations in assays with another strain of cells. We conclude that direct toxic effects on bone-marrow progenitor cells, in combination with the inhibition of cytokines involved in the regulation of haemopoiesis in certain susceptible individuals, may be responsible for idiosyncratic reactions to OPC-8212. PMID- 1623904 TI - Rebound of plasma vancomycin levels after haemodialysis with highly permeable membranes. AB - Vancomycin is usually given only once a week to haemodialysis (HD) patients. If highly permeable dialysis membranes are used, however, high clearance values have been reported, so the aim of the study was to determine whether high clearance of vancomycin resulted in sufficient drug elimination to induce subtherapeutic plasma levels after one week. In 18 chronic HD patients, treated with polysulfone dialyzers (1.2 m2), the pharmacokinetics of vancomycin were studied after administration of 1 g. Concentrations were determined by fluorescence polarisation immunoassay. At a blood flow of 219 ml.min-1, HD clearance of vancomycin was 62.3 ml.min-1. Immediately after dialysis plasma concentrations were 38% lower than predialysis levels. However, marked rebound in the vancomycin level was observed 5 h later, resulting in plasma levels only 16% lower than prior to dialysis. 3 HD treatments in 1 week removed about one third of the initial dose. After one week 15 of 18 patients still had a therapeutic plasma level (greater than 4 micrograms.ml-1). In conclusion, polysulfone membranes show high clearance of vancomycin. However, transfer of drug from blood to dialysate appears to be faster than from tissues to blood. Because of a marked rebound in plasma level after treatment, therapeutic drug concentrations will still be present in most patients after one week. PMID- 1623905 TI - Divergent effects of different enzyme-inducing agents on endogenous and exogenous testosterone. AB - The effects of three different enzyme-inducing drugs (antipyrine 1200 mg, phenobarbital 100 mg, rifampicin 600 mg per day for 7 days) on plasma and urinary testosterone concentrations, plasma gonadotropin levels, antipyrine kinetics, and urinary 6 beta-hydroxycortisol excretion were studied in 18 healthy volunteers. Changes in plasma and urinary testosterone concentrations following exogenous testosterone undecanoate (TU) were also investigated. Although both antipyrine and rifampicin increased antipyrine clearance by about 60%, they produced contrary effects on testosterone: antipyrine lowered the total morning plasma testosterone and plasma testosterone AUC following TU, while rifampicin led to increases of about 20% and 78%, respectively. By contrast, phenobarbital did not significantly alter the endogenous and exogenous plasma testosterone concentrations, but it increased the urinary excretion of testosterone by more than 60%. The other two enzyme inducers did not alter this parameter. Gonadotropin levels remained unchanged. The results indicate that different enzyme-inducing agents exert divergent effects on endogenous and exogenous testosterone concentrations and suggest that the effect of enzyme induction on endogenous testosterone depends on the type of microsomal enzyme-inducing drug used rather than on the extent of the induction achieved. PMID- 1623906 TI - A comparison of the relative sensitivities of factor VII and prothrombin time measurements in detecting drug interactions with warfarin. AB - We have studied the comparative abilities of the prothrombin time and factor VII clotting activity, measured using a chromogenic assay, to detect drug interactions with warfarin. Pharmacokinetic and pharmacodynamic data were collected from studies involving the single administration of 25 mg of warfarin in the absence and presence of fengabin, cimetidine, ranitidine, and enoxacin. Fengabin caused changes in both the pharmacokinetics and pharmacodynamics of warfarin, whereas cimetidine and enoxacin only caused changes in its pharmacokinetics. Ranitidine had no effect on either the pharmacokinetics or pharmacodynamics of warfarin. In general, factor VII clotting activity showed greater sensitivity but also greater variability than the prothrombin time to changes in clotting activity. Consequently, factor VII clotting activity did not have greater discriminatory power than the prothrombin time in detecting drug interactions involving warfarin. PMID- 1623907 TI - Dipyridamole increases human red blood cell deformability. AB - An automated filtration technique has been used to investigate the effect of dipyridamole (DP) on red blood cell deformability in patients identified as having rigid red cells. They were patients on haemodialysis (HD) for chronic renal failure (n = 18), patients with peripheral vascular disease (PVD, n = 23) and controls (hospital outpatients, n = 33). Leucocytes and platelets were removed from heparinised blood by filtration through Imugard wool. Washed red cell suspensions in buffer at 5% haematocrit, without or with 5 microM DP, were filtered through Nuclepore Hemafil Membranes with 4.7 microns pores. The initial steady state relative filtration pressure (iRFP) was used to assess cell deformability. A low iRFP value reflects increased deformability and vice versa. The mean iRFP values were 0.33, 0.393 and 0.403 for controls, PVD and HD patients respectively, indicating that the red cells in the two groups of patients were significantly more rigid. DP reduced the iRFP to 0.266, 0.278 and 0.263 for controls, PVD and HD patients respectively. The results suggest that DP may be beneficial when red cell rigidity contributes to impaired microvascular perfusion. PMID- 1623908 TI - Pharmacokinetic-pharmacodynamic modeling of the effects of clonidine on pain threshold, blood pressure, and salivary flow. AB - Although clonidine analgesia appears to be mediated by the same central alpha 2 adrenoceptors that mediate its hypotensive effect, it is short-lasting when compared to the fall in blood pressure. This has been investigated by combined pharmacokinetic-pharmacodynamic analysis in 10 healthy volunteers who received (double-blind and crossover) clonidine 200 micrograms orally + placebo i.v. and clonidine orally + naloxone i.v. (2.8 mg/5 h). Analgesia was assessed by measuring the subjective (VAS) and objective (RIII) pain thresholds after transcutaneous electrical stimulations of the sural nerve; the mean arterial blood pressure (MAP), salivary flow (SF), and plasma clonidine concentrations were also monitored. A combined pharmacokinetic (first order absorption - 1 compartment) - pharmacodynamic (linear) model, including a hypothetical effect compartment with and without tolerance, were fitted to the data. Clonidine and clonidine + naloxone increased subjective and objective pain thresholds for 4 h. The concentration-effect plot for MAP showed distinct hysteresis. The t1/2s for effect compartment equilibration were 29 and 42 min for clonidine + naloxone and clonidine. The concentration-effect curves for RIII had the same shape as MAP but the starting hysteresis suddenly collapsed, suggesting acute tolerance. The best fit was obtained with a model where the linear relationship between concentration in the effect compartment and analgesia changed acutely after the third hour. The short-lived analgesia was probably related to an acute change in pain sensitivity induced by food, suggesting that it is not mediated solely by the alpha 2 adrenoceptors responsible for hypotension. PMID- 1623909 TI - The postoperative pharmacokinetics of codeine. AB - The metabolism and systemic availability of codeine have been studied in 12 patients after cholecystectomy. They were given 20 mg codeine as an IV bolus dose on the first day after surgery and 50 mg codeine as a single oral on the fourth day after surgery. Codeine had a medium to high extraction ratio and a total plasma clearance of 10.8 (4.3) ml.min-1.kg-1. The clearance varied four-fold between subjects. All the patients were extensive metabolizers with regard to the debrisoquine/sparteine polymorphism, as tested using dextromethorphan as the probe drug. Nevertheless, the formation of morphine from codeine was very small and plasma morphine concentrations were below the detection limit of 3.3 nmol.l-1 (1 ng.ml-1). As a corollary, the morphine/codeine ratio in the the concentration time curves was less than 3% in all the patients. The systemic availability of codeine varied extensively between subjects (range 12-84%). This might partly explain differences in the dose of codeine required as an analgesic. PMID- 1623910 TI - The pharmacokinetics of fluconazole during haemodialysis in uraemic patients. AB - We have studied the pharmacokinetics of fluconazole in five patients on long-term haemodialysis. The single-pass extraction rate of the dialyzer was 59 (3.5)% (n = 4), and the serum concentration was reduced by haemodialysis for 3 or 4 h by 26 (3.2)% (n = 5) and 39 (2.2)% (n = 9) respectively. The estimated amount extracted by a dialysis of 4 h was 33 (3.2)% (n = 4) of the dose. During repeated administration the serum fluconazole concentration increased, reaching a plateau at about 4 times the peak concentration after the first dose. After discontinuing administration the serum fluconazole concentration fell by 25% in every 3 h dialysis session. We conclude that fluconazole should be given in the usual dose of 100 or 200 mg at the end of every haemodialysis session. PMID- 1623911 TI - The pharmacokinetics of nifurtimox in chronic renal failure. AB - The pharmacokinetics of nifurtimox, a drug used in the treatment of Trypanosoma cruzi infections, has been studied in seven patients with chronic renal failure undergoing haemodialysis, and in seven healthy subjects. Each subject took nifurtimox 15 mg.kg-1 orally and blood samples were obtained for 10 h after administration. Nifurtimox in serum was analyzed by HPLC. The patients with chronic renal failure had a higher Cmax than the control subjects due to a change in systemic availability. An alternative explanation would be that both the distribution volume and the clearance had changed. The mean half-life in the patients with chronic renal failure was similar to that in the healthy subjects. PMID- 1623912 TI - Effect of magnesium hydroxide on the absorption and efficacy of tolbutamide and chlorpropamide. AB - The effect of magnesium hydroxide on the absorption and efficacy of tolbutamide and chlorpropamide was examined in a total of 32 healthy volunteers in two separate, randomized parallel-group studies, with 16 subjects in each study. After an overnight fast, the first group of 8 volunteers ingested 500 mg tolbutamide or 250 mg chlorpropamide with 150 ml water, and the second group the same doses of the active drugs with 150 ml water containing 850 mg magnesium hydroxide. Magnesium hydroxide increased the area under the plasma tolbutamide concentration-time curve (AUC) from 0 to 1 h and from 0 to 2 h by 5-fold and 2.5 fold, respectively. The peak plasma concentration, peak time and total AUC were not significantly altered. The incremental insulin area and the decremental glucose area from 0 to 1.5 h were significantly larger in the magnesium hydroxide group than in the controls. The maximum insulin response to tolbutamide was increased fourfold by coadministration of magnesium hydroxide, and it occurred about 1 h earlier than in the control group. In addition, the maximum fall in plasma glucose concentration was attained about 1 h earlier in the antacid group. A tendency to an increased rate of chlorpropamide absorption was observed after magnesium hydroxide, but it did not appear to affect the insulin and glucose responses to chlorpropamide. It is concluded that magnesium hydroxide increased the early bioavailability of tolbutamide, resulting in enhanced insulin and glucose responses. A tendency toward accelerated chlorpropamide absorption by magnesium hydroxide was also observed, but the efficacy of chlorpropamide was unaffected. PMID- 1623913 TI - Inhibition of cyclooxygenase attenuates baroreceptor function and increases the pressor response to norepinephrine in man. AB - The possible influence of prostaglandins on baroreceptor function in man has been investigated. Baroreceptor reflex was activated by intravenous infusion of norepinephrine and the pressor response was measured, both before and after administration of indomethacin. Resting blood pressure remained unchanged after indomethacin while resting heart rate was significantly decreased as compared to placebo and the norepinephrine-induced rise in mean arterial blood pressure was significantly more pronounced. The baroreceptor-mediated decrease in heart rate tended to be smaller. Baroreceptor sensitivity (delta heart rate/delta blood pressure) was significantly reduced by indomethacin to about half of the control value. In addition to attenuation of sensitivity, the findings represent resetting of the baroreceptor setpoint and a more pronounced pressor response to norepinephrine after cyclooxygenase inhibition. Thus, eicosanoids originating via the cyclooxygenase pathway of arachidonate metabolism may modulate the vascular response to adrenergic stimulation and may participate in the regulation of baroreceptor reflex setpoint and sensitivity. PMID- 1623914 TI - Endoscopic evaluation of the effect of ketoprofen, ibuprofen and aspirin on the gastroduodenal mucosa. AB - Endoscopic lesions of the gastric mucosa were evaluated in 12 healthy volunteers after administration of single doses of ketoprofen (25 mg), ibuprofen (200 mg) and aspirin (500 mg) in a randomized, double-blind, cross-over study. The grades of the lesions (according to Lanza's scale) were lower after the administration of ketoprofen than aspirin and were comparable to ibuprofen. An endoscopic score greater than 1 was observed in 3 cases after ibuprofen or ketoprofen, and in 8 cases after aspirin. At a time when low, single doses of NSAIDs are widely used as analgesics, gastroscopy makes it possible directly to assess the local aggressivity of these molecules. In this way it was possible to demonstrate that the local toxicity of NSAIDs was lower than that of aspirin. PMID- 1623915 TI - Pharmacokinetics of diphemanil methylsulphate in healthy subjects. AB - The pharmacokinetic parameters of oral diphemanil methylsulphate have been evaluated in six healthy male volunteers. Absorption of the drug was slow (tmax = 2 to 4 h), the mean half-life was 8.35 h, and the amount of the drug recovered in urine within 48 h ranged from 0.6 to 7.4% of the administered dose. The results suggest low bioavailability, assuming that the drug is poorly metabolized. PMID- 1623916 TI - Dose proportionality study of loperamide following oral administration of loperamide oxide. AB - The pharmacokinetics of loperamide, after oral administration of increasing doses (1 to 16 mg) of loperamide oxide, has been investigated in 10 healthy male volunteers, using a randomised cross-over design. Comparison of the maximum plasma loperamide concentration and AUC demonstrated that the bioavailability of loperamide was proportional to the dose of loperamide oxide administered. PMID- 1623917 TI - Secretion of the antidiarrhoeal agent loperamide oxide in breast milk. PMID- 1623918 TI - Anti-arthritic effects demonstrated by an interleukin-2 receptor-targeted cytotoxin (DAB486IL-2) in rat adjuvant arthritis. AB - DAB486IL-2 is an interleukin-2 receptor-specific cytotoxin which selectively targets and kills cells which bear the high-affinity form of the IL-2 receptor. Since elimination of activated T lymphocytes may be useful in the treatment of rheumatoid arthritis, the effect of DAB486IL-2 treatment in an animal model of arthritis was investigated. We demonstrated that rats treated with DAB486IL-2 during the induction phase of disease have delayed onset of symptoms and significantly reduced severity of inflammation as well as a depressed proliferative response to mycobacterial stimulation in vitro. In addition, the presence of preexisting antibodies to the molecule had no impact on the anti arthritic effects observed in this model. These data suggest that DAB486IL-2 may have therapeutic potential in the treatment of rheumatoid arthritis. PMID- 1623919 TI - A V region-connected autoreactive subfraction of normal human serum immunoglobulin G. AB - Mouse and human natural IgM autoantibodies have been shown to be polyreactive and "connected" through V region-dependent interactions. In the present study, we have identified a connected subfraction of normal human serum IgG by using affinity chromatography of F(ab')2 fragments of pooled IgG (IVIg) or of IgG from a single donor on Sepharose-bound F(ab')2 fragments of the same source of IgG. The connected fraction of IgG exhibited a high content of autoantibodies directed against a wide panel of evolutionarily conserved self antigens and of self antigens that may be targets of autoantibodies in autoimmune diseases. Connected IgG also contained higher amounts of antibodies directed against commonly encountered microbial antigens than unfractionated IgG. The connected fraction did not, however, differ from unchromatographed IgG nor from non-connected IgG in its content of antibodies to vaccinal antigens and to distant foreign antigens. Thus, in humans as in mice, connectivity is a prominent feature of autoantibodies. Our observations are suggestive of a tight control by IgG of the expressed autoreactive repertoire in healthy individuals and strengthen the concept that the therapeutic infusion of pooled normal IgG (IVIg) may be effective in autoimmune diseases by bringing to patients normal regulatory components of the immunoglobulin network. PMID- 1623920 TI - Analysis of immunoglobulin variable region genes from human IgG anti-DNA hybridomas. AB - The molecular mechanisms leading to anti-double-stranded (ds) DNA antibody production in systemic lupus erythematosus (SLE) are poorly understood. We describe here the immunoglobulin variable region genes of six human hybridomas secreting IgG anti-dsDNA antibodies derived from three SLE patients. The monoclonal IgG anti-dsDNA antibodies have been shown to be of high affinity and no multireactivity was observed (Winkler et al., Clin. Exp. Immunol., 1991. 85: 379). The comparison of the variable region genes expressed in the hybridomas with known germ-line genes as well as with the germ-line counterparts from one patient shows that the VH and VL sequences are somatically mutated. The pattern and extent of the observed somatic mutations are suggestive for an antigen-driven selection of at least four of these B cell clones. Several VH and VL genes used by the hybridomas were found to be expressed in the natural antibody repertoire, in the restricted fetal repertoire and in B cell malignancies expressing the CD5 antigen. PMID- 1623921 TI - Interleukin-4-mediated tumor suppression in nude mice involves interferon-gamma. AB - The molecular events during the anti-tumor response induced by interleukin (IL)-4 were investigated by quantitative polymerase chain reaction. The growth of Chinese hamster ovary cells transfected to produce IL-4 (CHO.T1) was strongly suppressed when cells were injected intraperitoneally into nude mice and this suppression was accompanied by the rapid accumulation of activated macrophages. Peritoneal cells from such mice were analyzed for mRNA induced by IL-4. Correlating with a high local IL-4 concentration, several transcripts were found to be up-regulated during the early phase of the anti-tumor response [IL-4 receptor, IL-5, tumor necrosis factor (TNF) and interferon (IFN)-gamma]. The functional relevance of the elevated mRNA levels was analyzed by injection of CHO.T1 cells together with anti-cytokine monoclonal antibodies (mAb). In contrast to anti-IL-5 and anti-TNF mAb, an anti-IFN-gamma mAb interfered with the anti tumor response demonstrating the involvement of IFN-gamma during the IL-4-induced tumor suppression. Tumor growth in anti-IFN-gamma mAb-treated animals was significantly delayed in comparison to anti-IL-4 mAb-treated mice, suggesting that IFN-gamma-independent effector cells may also be involved. PMID- 1623922 TI - Human peripheral blood leukocytes transplanted on CB17 scid-scid mice are transferred to their offspring. AB - Severe combined immunodeficient (scid) mice are deficient in functional T cells and B cells. Hence, scid mice reconstituted with human peripheral blood leukocytes (scid-huPBL) provide an excellent model for analysis of the human immune response under in vivo conditions. We have investigated this model further by analyzing human immune responses in the progeny of scid-huPBL (termed scid humo). We find markedly elevated levels of human immunoglobulins (Ig) in the serum of scid-humo for more than 12 weeks indicating materno-fetal transfer of human B lymphocytes. Consistent with this finding we obtained evidence for the existence of human lymphocytes in scid-humo. Murine Ig levels in scid-humo were also elevated and surface Ig-expressing cells (probably B cells) were demonstrable. In this respect scid-humo resembled "leaky" scid. In contrast to "leaky" scid, scid-humo accepted transfer of human blood leukocytes. Not only leukocytes from autologous but also those from heterologous donors were accepted. Human Ig levels in scid-humo increased more rapidly as compared to normal scid mice. Thus, despite these increased B cell activities in scid-humo, transferred human leukocytes were not affected indicating that materno-fetal transfer of human cells had caused tolerization or conditioning. This is in contrast to scid mice in which elevated Ig levels correlate with increased failure rates of reconstitution with human blood leukocytes. We propose that scid-humo provide an improved model for studying the human immune responses in an in vivo setting. PMID- 1623923 TI - An anti-B cell autoantibody from Wiskott-Aldrich syndrome which recognizes i blood group specificity on normal human B cells. AB - We previously identified IgM autoantibodies in the sera of patients with Wiskott Aldrich syndrome (WAS) that react with a subset of normal human B lymphocytes and induce B cell differentiation in vitro. From splenocytes of a patient with WAS we generated heterohybridomas (HY18 and HY21) and a lymphoblastoid cell line (LWA10) that produce human IgM lambda or IgM kappa anti-B lymphocyte autoantibodies, respectively. Immunohistochemical and multiparameter flow cytometric analyses demonstrate that these autoantibodies are specific for lymphocytes of the B lineage and preferentially stain B cells that reside in the mantle zone of secondary follicles and that constitutively co-express the CD5 surface antigen and most major autoantibody-associated cross-reactive idiotypes; in addition, these antibodies stain most pre-B cells in adult bone marrow. Molecular studies show that these anti-B lymphocyte autoantibodies are encoded by a highly conserved VH4 gene, designated VH4.21. The gene encodes a number of autoantibodies, especially anti-i and anti-I IgM cold agglutinins. Hemagglutination and surface labeling studies reveal that HY18 and LWA10 recognize the "i" carbohydrate antigenic determinant(s) which is classically found on human cord red blood cells and, as shown now by this study, on a subpopulation of human B cells which expresses it early in B cell development. These studies raise the possibility that the gene product encoded by this highly conserved germ-line VH4 gene may play a physiological role in B cell development and/or differentiation. PMID- 1623924 TI - Specificity, T cell receptor diversity and activation requirements of CD4+ and CD8+ clones derived from human melanoma-infiltrating lymphocytes. AB - To try to understand the functional significance of human melanoma-infiltrating lymphocytes (TIL), a clonal analysis of the specificity, T cell receptor (TcR) diversity and activation requirements of these lymphocytes isolated from four different tumors was carried out. Supporting the presence of in vivo primed tumor specific T lymphocytes in these four tumors, a high frequency of the Cd8+ and CD4+ clones, obtained from the TIL cultured for a few days with recombinant interleukin (rIL)-2 and autologous tumor cells, exhibited a restricted lysis or proliferation in response to the autologous tumor cell line. In contrast, no tumor-specific clone was obtained from freshly extracted TIL, suggesting that the frequency of tumor-specific effectors remained low in these tumors. Only the CD8+ clones lysed the autologous tumor cells and their activity was major histocompatibility complex MHC class I restricted. Significant expansion of CD4+ and CD8+ tumor-specific clones required regular restimulation by autologous melanoma cells but also the addition of exogenous IL-2 and of Epstein-Barr virus transformed B feeder cells. Five different tumor-specific clones, three CD8+ and two CD4+ clones were identified in a single tumor on the basis of their TcR gene configuration. Together, these data suggest that a spontaneous and diverse immune response, mediated by tumor-specific CD4+ as well as CD8+ T lymphocytes, arises in most MHC-bearing human melanomas but that antigen-MHC complex presentation by tumor cells does not, at least in vitro, allow a significant proliferation of these lymphocytes. PMID- 1623925 TI - Immunosuppression by lymphocytic choriomeningitis virus infection: competent effector T and B cells but impaired antigen presentation. AB - Lymphocytic choriomeningitis virus (LCMV) may cause a severe immunosuppression in mice. Its pathogenesis is apparently dependent on LCMV-specific CD8 effector T cells that mediate the destruction of virus-infected cells which are normally essentially involved in immune responses. Evaluation of various LCMV isolates in this study established a general correlation between their tropism for lymphohemopoietic cells and immunosuppression. When immune responses were assessed as the capacity of mice to mount an anti-vaccinia virus cytotoxic T cell response or an IgG response to vesicular stomatitis virus (VSV), after a primary LCMV infection, LCMV-Armstrong, WE, Clone 13 and Docile were increasingly immunosuppressive in a dose-dependent fashion with respect to both extent and duration. Analysis of lymphocyte subpopulations showed variable effects of the various LCMV isolates that did not reveal patterns readily explaining immunosuppression. To evaluate whether LCMV infection affected T and/or B cell functions directly or whether antigen presentation was impaired, adoptive transfer experiments were performed. Untreated or irradiated but uninfected normal recipient mice receiving adoptively transferred T or B cells from LCMV-WE or Docile-infected immunosuppressed donor mice responded within 30%-100% of normal ranges in both assay systems. In contrast, when T or B cells from normal donors were transferred to irradiated or non-irradiated LCMV-immunosuppressed recipients, they failed to mount a significant cytotoxic T cell response against vaccinia virus or an IgG response to VSV. Thus, the T and B cells from LCMV immunosuppressed mice were able to function within normal ranges; in contrast, histologically and functionally, antigen presentation was severely impaired in LCMV-immunosuppressed mice. PMID- 1623926 TI - The murine IgG1/IgE class switch program. AB - Immunoglobulin class switching is controlled by cytokines. Thus, interleukin-4 (IL-4) directs class switching to both IgG1 and IgE. Consistent with this are the results reported here on restriction endonuclease analysis of active and inactive alleles of the IgH locus in IgE-producing cells. In cells that were stimulated in vitro by lipopolysaccharide and IL-4 the silent alleles preferentially switched to gamma 1, whereas in cells that were stimulated by antigen in vivo both active and inactive alleles switched to epsilon. Thirty percent of the recombined switch regions (S mu/S epsilon) contain S gamma 1 sequences, which we interpret as footprints of a previous switch to gamma 1. Since this percentage is a minimum estimate, between 30% and 100% of switching to epsilon must occur sequentially via gamma 1. PMID- 1623927 TI - Electroporation of exogenous antigen into the cytosol for antigen processing and class I major histocompatibility complex (MHC) presentation: weak base amines and hypothermia (18 degrees C) inhibit the class I MHC processing pathway. AB - While endogenous antigens are presented by class I major histocompatibility complex (MHC) molecules, exogenous antigens generally require a means for penetration into the cytosol for processing prior to class I MHC presentation. We have optimized conditions for electroporation as a means to experimentally introduce exogenous antigens into the cytosol, providing a system with a number of advantages for dissecting the class I MHC processing pathway. Presentation was assessed by the response of class I or class II MHC-restricted T hybridoma cells. Essentially instantaneous antigen delivery by electroporation facilitated kinetic analysis of the class I pathway and investigation of the effects of various inhibitors or hypothermic conditions on class I MHC antigen processing. This pathway was inhibited by weak base amines (e.g. chloroquine and NH4Cl), cycloheximide, and hypothermia (18 degrees C, which inhibits certain intracellular vesicular processing pathways). The electroporation technique provides a simple, consistent approach for rapid cytosolic antigen delivery for analysis of class I MHC processing. PMID- 1623928 TI - Regulation of interleukin-2 responses by phosphatidic acid. AB - Interleukin-2 (IL-2) plays a central role in the immune system by regulating the proliferation and differentiation of T lymphocytes. However, the molecular mechanism of the signal transduction through the IL-2 receptor is poorly understood. We have studied the role of phosphatidic acid (PA) on IL-2 signal transduction using cloned T lymphocytes. IL-2 stimulated a transient increase in the PA concentration in resting CTLL-2 cells prelabeled with [3H]palmitic acid. This effect was detected as early as 1 min after IL-2 addition and peaked at 5 min. IL-2 similarly increased phospholipase D activity in intact CTLL-2 cells, as inferred by phosphatidylethanol production. By contrast, IL-2 did not affect [3H]palmitic acid-labeled diacylglycerol levels. Furthermore, exogenous addition of several natural or synthetic PA to T cells mimicked IL-2 activity. Thus, PA were able to induce DNA synthesis on CTLL-2 cells, although this effect was only 10%-20% of that observed with IL-2. PA showed a synergistic effect with low doses of IL-2. In addition, PA was able to induce c-myc RNA transcription in CTLL-2 cells as well as IL-2 receptor (CD25) expression on the cell membrane with equal potency as saturating doses of IL-2. It is likely that IL-2-induced PA accumulation is a consequence of phospholipase D activation. This hypothesis is further supported by the fact that the addition of exogenous phospholipase D but not phosphatidylinositol-specific phospholipase C also reproduced the IL-2 or PA effects mentioned above. In summary, our results suggest a role of phospholipase D activation and PA formation as second messengers of IL-2 activity. PMID- 1623929 TI - The use of a non-depleting anti-CD4 monoclonal antibody to re-establish tolerance to beta cells in NOD mice. AB - The use of immunosuppressive drugs in the management of autoimmunity penalizes a large part of the immune system for the misdemeanors of a small minority of T cells. An ideal form of therapy would be one in which it were possible to render the immune system tolerant of the inciting antigens with minimal effects on other responses. We here show that it is possible to re-establish self tolerance in an animal model of insulin-dependent diabetes mellitus without prior deletion of CD4+ T cells using a short course of therapy with a non-lytic monoclonal antibody to the CD4 adhesion receptor on T cells. This tolerance can be achieved even when diabetogenic cells are already in the pancreas. Primary responses to antigens given after therapy has ceased are normal and secondary responses to antigens seen prior to, but not during, the period of antibody therapy can remain unaffected. This suggests that intervention with selected CD4 antibodies may have significant advantages over and above that provided not only by conventional immunosuppression but also over that provided by a depleting antibody. PMID- 1623930 TI - Eosinophil as antigen-presenting cell: activation of T cell clones and T cell hybridoma by eosinophils after antigen processing. AB - We have studied the role of murine eosinophils as antigen-presenting cells (APC). Eosinophils have several characteristics that support the hypothesis of its function as potential APC: they have phagocytic capacity, express adhesion molecules and major histocompatibility complex (MHC) class II antigens and can produce and release interleukin-1 (IL-1). We have obtained several T cell clones specific for Mesocestoides corti antigens and used T cell hybridoma specific for ovalbumin (OVA) to test this hypothesis. Granulocyte-macrophage colony stimulating factor-activated pure eosinophils (99.9%), express class II antigens and are able to present M. corti antigens to specific T cell clones or OVA to T cell hybridoma 3DO 11.10, inducing the proliferation of T cell clones and IL-2 release by the T cell hybridoma. Proliferation of T cells clones is dependent on the number of eosinophils used as APC. We have compared the efficiency of the same number of macrophages and eosinophils as APC, and have found that macrophages are more efficient than eosinophils. Lysosomotropic agents, such as chloroquine and ammonium chloride, that inhibit antigen processing, impaired eosinophil presentation. This presentation is restricted by MHC class II and inhibited by anti-I-Ad monoclonal antibody. The present study provides clear evidence of APC function for eosinophils. Our investigation points to a new role for eosinophils in the immune response. PMID- 1623931 TI - Low-molecular weight B cell growth factor (BCGF-12KD) as an autocrine growth factor in B cell chronic lymphocytic leukemia. AB - The role of cytokines in the growth and spreading of human hematologic malignancies has been underlined in recent years. Here we report evidence that a human 12-kDa B cell growth factor (BCGF-12KD) may function as a growth stimulatory factor in B cell chronic lymphocytic leukemia (B-CLL). First, recombinant BCGF-12KD induced dose-dependent DNA synthesis in neoplastic B cells of four B-CLL patients tested. Second, seven different B-CLL clones secreted a BCGF-12KD-like product that accounted for their proliferation. A neutralizing monoclonal antibody (mAb; Ac8) directed against a BCGF-12KD synthetic peptide inhibited the spontaneous growth of the leukemic B cells. The same mAb blocked DNA synthesis in normal tonsillar B lymphocytes induced by the culture supernatant of spontaneously proliferating B-CLL cells. Finally, BCGF-12KD mRNA was expressed in freshly isolated (two of three patients) as well as in vitro proliferating B-CLL cells (three of three patients). These findings strongly suggest that BCGF-12KD can modulate the growth of B-CLL cells in vivo as well as in vitro. They may offer significant insights into the biology of this frequent B lymphoproliferative disorder. PMID- 1623933 TI - Complexes of IgG molecules and C3a and C4a complement components in human serum. AB - A heterogeneous group of proteins was separated from human serum IgG using 5 M guanidine hydrochloride solution in 0.1 M acetic acid. The protein mixture was fractionated by reverse-phase high-performance liquid chromatography and two proteins were isolated and identified as the C3a and C4a complement components (anaphylatoxins) according to their molecular masses and N-terminal sequences. Using a chemical cross-linking technique, the capacity of C3a and C4a to reassociate with the heavy and the light chains of IgG was shown. On the basis of the molecular masses of reconstituted complexes one molecule of C3a (or C4a) was bound to one heavy or one light chain of IgG. PMID- 1623932 TI - In vivo responses of CD4+ and CD8+ cells to bacterial superantigens. AB - Staphylococcal enterotoxin B (SEB) is a bacterial superantigen that binds to major histocompatibility complex (MHC) class II molecules and specifically activates T cells bearing V beta 8 T cell receptor domains. We have compared several aspects of the response of CD4+ and CD8+ T cell subsets to SEB in vivo. V beta 8+ cells in both subsets proliferated to a similar extent upon SEB injection. Furthermore, mRNA for interferon-gamma was induced in both subsets with similar kinetics and SEB dose-response. Finally CD8+ (but not CD4+) T cells from SEB-injected mice exhibited SEB-specific lysis of MHC class II-bearing target cells. Collectively, these data indicate that the CD4: MHC class II interaction confers no detectable selective advantage to CD4+ cells in the in vivo response to SEB. The observed effector functions of both subsets may contribute to SEB-induced immunopathology. PMID- 1623934 TI - Synthesis of retinoic acid from retinol by cultured rabbit Muller cells. AB - Previous observations have shown that Muller glial cells of the vertebrate retina contain cellular retinoid-binding proteins, that the retina contains retinoic acid, and that cellular retinoic acid-binding protein is present in amacrine neurons (and, in some species, Muller cells) within the retina. These findings led to the suggestion that Muller cells may synthesize retinoic acid and release it for use by other retinal cells. To test this possibility, we cultured Muller cells from adult rabbit retinas, incubated the cultures with radioactive retinol, and identified and quantified the resultant radioactive retinoids by HPLC. Retinaldehyde was rapidly synthesized from retinol, reaching a plateau of 1-2 pmol mg-1 cell protein by 30 min. Retinoic acid initially accumulated more slowly, but by 30 min constituted most of the synthesized retinoid. While the retinaldehyde remained within the cells, retinoic acid was rapidly released into the medium; extracellular retinoic acid exceeded the intracellular amount after 30 min of incubation. Smaller amounts of retinyl esters were also synthesized and retained by the cells. These results are consistent with the suggestion that Muller glia are a source of retinoic acid in the retina. The synthesis of retinoic acid by these cells, and the presence of retinal neurons that contain cellular retinoic acid-binding protein, raise the possibility that retinoic acid plays a role in the retina, although this role is not presently known. Furthermore, these results may have implications for other parts of the adult nervous system. Adult brain contains retinol- and retinoic acid-binding proteins, and, therefore, may also be a site of retinoic acid metabolism. Because of the relatively simple cellular organization of the retina and its demonstrated capacity to synthesize retinoic acid, the retina may be a system of choice for further studies of the synthesis and function of retinoic acid in adult neural tissue. PMID- 1623935 TI - Calbindin D-28k and parvalbumin immunohistochemistry in developing rat retina. AB - The developmental profiles of two calcium-binding proteins, calbindin-D28k (CaBP) and parvalbumin (PV), were investigated immunohistochemically in the developing rat retina. CaBP-immunoreactivity appeared first on embryonic day 17 in the horizontal, amacrine and ganglion cells; on embryonic day 21 in the inner plexiform layer; and on post-natal day 6 in the outer plexiform layer. The reaction intensity had increased to its maximum level by post-natal day 10. PV immunoreactivity was first noted on embryonic day 19 in the amacrine and ganglion cells and reached its maximum on post-natal day 10. Two distinct subpopulations of amacrine cells were clearly recognized after post-natal day 6; one was positive for CaBP and the other for PV. Some morphological differences were noted between the two. PMID- 1623936 TI - Polypeptide profiles of normal and inflamed rabbit aqueous humor: identification of catabolic products of immunoglobulin G in the normal eye. AB - The anterior segment of the eye is isolated from the bloodstream by anatomic barriers. These barriers break down during inflammation elicited by muramyl dipeptide (MDP), a component of the cell walls of bacteria. The protein composition of normal aqueous humor and inflamed aqueous were characterized using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. The presence of transferrin, albumin, IgG and IgM were demonstrated in normal and inflamed aqueous. Normal aqueous additionally contained seven polypeptides (35, 31, 29, 25, 22, 21 and 19 kDa, respectively) that were not observed in inflamed aqueous. Four of these peptides (31, 29, 25 and 19 kDa) were identified as fragments of IgG heavy chains based on their reactivity with anti-IgG antibodies and staphylococcal protein A. Immunoglobulin catabolism has been noted to occur in tissues diffusely throughout the body; this is the first report of it occurring in the eye. This phenomenon appears to be circumvented on breakdown of the blood-aqueous barrier. These observations may relate to the immunoprivilege of the eye and its modulation in inflammation. PMID- 1623937 TI - Prevention of cataract in diabetic rats by aspirin, paracetamol (acetaminophen) and ibuprofen. AB - Evidence from epidemiological, in vitro and animal studies has accumulated to support the idea that aspirin, ibuprofen and paracetamol protect against cataract. In this study rats made diabetic with streptozotocin were given these drugs in their drinking solution for up to 160 days. All three drugs delayed cataract formation assessed by slit-lamp examination for a large part of this time. Blood glucose levels were a little lower in diabetic rats treated with aspirin and ibuprofen than in untreated diabetic rats although all groups remained diabetic. Similarly, the increased glycation (non-enzymic glycosylation) of lens proteins caused by diabetes was less in the diabetic rats treated with aspirin and ibuprofen. The fall in glutathione induced by diabetes was also alleviated by aspirin and ibuprofen. Paracetamol appeared to afford similar protection against the biochemical changes but its effect was not statistically significant. The decrease in glutathione and increase in glycation were related to the progression of lens opacification. The greatest loss of glutathione occurred at an early stage, whereas glycation had its greatest change at the later stages--nuclear and mature cataract. These results encourage the view that ibuprofen, aspirin and paracetamol could protect against cataract in man: a hypothesis that could be tested in a properly-conducted clinical trial. PMID- 1623938 TI - Effect of EGF on the corneal wound healing of alloxan diabetic mice. AB - We identified the local treatment effect of epidermal growth factor on corneal wound healing of alloxan diabetic mice. The corneal wounds were induced by 0.5 M NaOH solution on the corneal surfaces of the diabetic and non-diabetic groups. The local epidermal growth factor solution (100 ng ml-1) was dropped in 5 microliters aliquots into the eye twice a day. The corneal wounds were measured daily for 15 days and examined histologically at the end of 15th day of experimental period. The results indicated that topical epidermal growth factor treatment of diabetic and non-diabetic mice greatly improved the incidence of healing of wounded corneas. PMID- 1623939 TI - Does the lens serve as a 'sink' for iron during ocular inflammation? AB - Twenty-four hours after induction of ocular inflammation by intravitreal injection of endotoxin (10 ng), the intraocular fluid (IOF, aqueous and vitreous humors) concentration of iron (Fe) increased. This was presumably due to entry of the plasma Fe-binding protein, transferrin, into the IOFs through disrupted blood ocular barriers. After 1 day of inflammation the Fe concentration in lenses from the inflamed eye was 60% greater than that measured in contralateral control lenses. By day 15, lens Fe concentration had returned to levels of the contralateral control lenses. There was a distinct relationship between the dose of endotoxin used and the amount of Fe accumulated by the lens. The Fe concentration in lenses from eyes injected with 100 ng endotoxin was 0.376 +/- 0.027 micrograms g-1 wet weight compared to 0.214 +/- 0.014 micrograms g-1 in lenses from eyes injected with 0.25 ng endotoxin. In a previous study, copper (Cu) concentration in the IOFs was elevated to the same extent as Fe in response to intravitreal injection of endotoxin. However, in the present study, lenticular Cu concentration was unaltered at the highest (100 ng) dose of endotoxin. Since the increase in lens uptake was selective for Fe, there may be a specific Fe uptake mechanism in this ocular tissue. The physiological reasons for and possible pathological consequences of such a process are discussed. PMID- 1623940 TI - Contractile cells in the human scleral spur. AB - The scleral spur in 37 human (age 17-87 years) and six cynomolgus monkey eyes (2 4 years) was investigated. Serial meridional and tangential sections were studied with ultrastructural and immunocytochemical methods. The bundles of the ciliary muscle do not enter the scleral spur, but their tendons, which consist of elastic fibres join the elastic fibres in the scleral spur. Within the scleral spur a population of circularly oriented and spindle-shaped cells is found. In contrast to the ciliary muscle cells, the scleral spur cells form no bundles, but are loosely aggregated. They have long cytoplasmic processes and are connected to each other by adherens-type and gap junctions. They stain intensely for alpha smooth muscle actin, myosin and vimentin. In contrast to the ciliary muscle cells, they do not stain for desmin. Ultrastructurally, the scleral spur cells contain abundant thin (actin) filaments, but do not otherwise show the typical ultrastructural features of ciliary muscle cells. The scleral spur cells do not express a complete basal lamina. They form individual tendinous connections with the elastic fibres in the scleral spur, which are continuous with the elastic fibres of the trabecular meshwork. The scleral spur cells are in close contact with nerve terminals containing small agranular (30-60 nm) and large granular (65 110 nm) vesicles but also with terminals containing small granular (30-60 nm) vesicles which are regarded as typical for adrenergic terminals. We conclude that the scleral spur cells are contractile myofibroblasts. Their contraction might influence the rate of the aqueous outflow. PMID- 1623941 TI - Temporally correlated expression of nAChR genes during development of the mammalian retina. AB - In situ hybridizations and RNase protection assays have been used to characterize nicotinic acetylcholine receptor (nAChR) gene expression in the developing and adult rat retina. At the earliest time examined (embryonic day 13) a low level of alpha-3 and beta-4 gene expression could be detected. During the next 48 hr there was a dramatic induction of the alpha-3, alpha-4, beta-2, beta-3 and beta-4 genes in the recently differentiated retinal ganglion cells. By post-natal day 4 we detected nAChR gene expression in the inner nuclear layer. In the adult retina, in situ hybridizations showed these genes are expressed by cells residing in the ganglion and inner nuclear layers. These results suggest a common regulatory mechanism for the induction of nAChR expression in retinal ganglion cells during development. In addition, the variety of nAChR genes expressed in the retina imply a relatively large number of different types of nAChRs can be expressed by these cells. PMID- 1623942 TI - The effect of urea on the aggregate state and elastase inhibitor activity of the water-insoluble fraction from bovine and human lens. AB - Preparations of alpha-crystallin from bovine and human lens exhibited elastase inhibitor activity with a specific activity of 100-250 U mg-1 protein. A washed water-insoluble fraction from bovine, human and cataractous lens nuclei, when solubilized by sonication, gave specific activities of 910, 950 and 1270 U mg-1, respectively. Disaggregation of these water-insoluble fractions in 8.0 M urea, with subsequent reaggregation by urea removal, resulted in a decrease in inhibitor activity. Agarose A-5m gel filtration chromatography after the urea treatment resolved a residual high molecular weight (HMW) fraction and a peak which eluted at the position of water soluble alpha-crystallin. Assays showed that the urea-induced 'alpha-crystallin' peaks from all three preparations had specific activities, equivalent to native alpha-crystallin, whereas the HMW fractions retained their original high specific activity. We conclude that the increased elastase inhibitor activity of the water-insoluble fraction is a property of the aggregate state of the component alpha-crystallin molecules, which is lost upon reaggregation to an 800-kDa alpha-crystallin. Amino acid analysis of the bovine water-insoluble fraction suggested a content of 85-90% alpha-crystallin and 10-15% beta H-crystallin, which was confirmed by SDS PAGE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623943 TI - Dexamethasone ameliorates retinal photic injury in albino rats. AB - The effect of dexamethasone in two regimens on retinal photic injury was studied in Lewis albino rats that were exposed to 24 hr of continuous green fluorescent light. Under regimen 1, dexamethasone was given at a daily dosage of 1 mg kg-1 for 8 days, starting 6 days before light exposure. Under regimen 2, dexamethasone was given at the same daily dosage for 3 days, started 1 day before light exposure. Pathologic study of the light-exposed retina, morphometric evaluation of the photoreceptor cell loss, cell counts of the macrophages in the subretinal space, and measurements of rhodopsin levels were undertaken in the dexamethasone treated and control retinas at various times. The administration of dexamethasone in both regimens did not produce pathologic changes in the retina before light exposure, but rhodopsin levels were significantly lowered in both treated groups when compared to corresponding vehicle treated control animals. Under regimen 1, at 6 hr after light exposure, both the treated and the control groups showed comparable loss of photoreceptor cells, degeneration of the photoreceptor elements and retinal pigment epithelium, but a significantly lowered level of rhodopsin in the treated group was noted. At 6 days after exposure, the outer nuclear layer thickness, and the outer and inner segments showed significant preservation in the treated group. Also in the treated group, the number of macrophages was significantly reduced and the retinal pigment epithelial (RPE) vacuolation was markedly less. However, there was no difference in rhodopsin levels. At 14 days after exposure, the outer nuclear layer thickness and rhodopsin levels of the treated rats had significantly higher values than the controls. Under regimen 2, however, at 6 days after exposure, an ameliorative effect in the RPE was observed but there were no differences of rhodopsin levels, the outer nuclear thickness and number of macrophages between the treated and control groups. Regimen 1 was associated with a significantly higher retinal level of dexamethasone when compared with regimen 2. The ameliorative effect of dexamethasone on rat retinal photic injury may be through inhibition of lipid peroxidation, in which a high retinal level of the steroid is required. PMID- 1623945 TI - Flavin levels in the rat retina. AB - Exposure of riboflavin and its coenzymes adenine dinucleotide (FAD) and riboflavin-5'-phosphate (FMN) to UV and visible light results in the generation of radicals and photodegradative products that can damage surrounding macromolecules. Vertebrates and invertebrates have lost the ability to synthesize riboflavin and must obtain it or its coenzymes from food. The present study evaluated the relationship between FAD, FMN, and riboflavin concentrations in retina and blood of male Sprague-Dawley rats. Rations were provided in the form of purified diets containing 0, 3, 6, 30, and 300 mg riboflavin kg-1 diet. Analysis of flavins by HPLC showed that saturation levels of FAD, FMN and riboflavin in the retina and blood were achieved with diets containing 3 mg riboflavin kg-1. Retinal flavins were not significantly elevated by further increases in dietary riboflavin concentration, but an unidentified flavin appeared in the blood of rats given rations containing concentrations above 3 mg kg-1. The concentration of this unknown flavin varied in proportion to the level of dietary riboflavin. PMID- 1623944 TI - Modulation of macrophage colony stimulating factor in cultured human retinal pigment epithelial cells. AB - Steady-state mRNA expression and protein production of macrophage colony stimulating factor were measured in visually confluent monolayers of unstimulated cultured human retinal pigment epithelial cells and after cells were stimulated with recombinant cytokines. Using reverse transcription polymerase chain reaction, macrophage colony stimulating factor mRNA expression was detected in unstimulated cells obtained from each of four separate donors. In these cells, mRNA expression was accompanied by secretion of macrophage colony stimulating factor protein into cell-conditioned medium; 48 hr after cells were switched to fresh medium, the mean (+/- S.D.) quantity of macrophage colony stimulating factor, measured by enzyme-linked immunoassay, was 5.1 +/- 2.3 ng 10(-6) cells. There was a dose- and time-dependent induction of macrophage colony stimulating factor mRNA after cells were exposed to recombinant human interleukin-1 and tumor necrosis factor alpha. Maximal mRNA induction was observed in cells exposed for 4 hr to interleukin-1 beta (5 U ml-1) or for 4-8 hr to tumor necrosis factor alpha; under these conditions, macrophage colony stimulating factor mRNA was induced up to 23- and 46-fold after exposure to interleukin-1 beta and tumor necrosis factor alpha, respectively. Similarly, macrophage colony stimulating factor protein production was enhanced after cells were exposed to recombinant cytokines. Protein secretion increased 1.3-2.5-fold (P less than 0.001) after exposure to interleukin-1 beta (5 U ml-1), and 1.2-1.6-fold after exposure to tumor necrosis factor alpha (P less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623946 TI - Progressive modifications of mouse lens crystallins in cataracts induced by buthionine sulfoximine. AB - L-buthionine-S,R-sulfoximine (BSO), a specific inhibitor of GSH biosynthesis, was administered four times daily to mouse pups on post-natal days 7 and 8, inducing initiation of opacification on day 9. The initial progression of the cataract (less than 24 hr) was divided into four stages: (1) developing floriform; (2) mature floriform; (3) degenerate floriform; and (4) amorphous translucent cataract. Following this, dense corticonuclear opacities developed within several days. Two-dimensional gel electrophoresis of water-soluble whole lens extracts indicated that the most rapid early cataractous changes, occurring mainly during stage 2, were loss of the two major components of the heavy beta-crystallin fraction, a 31-kDa basic polypeptide and an acidic component at 27 kDa, concomitant with the appearance of new species at 30 and 25 kDa. This was followed by more extensive modification of both alpha and beta-crystallins during stages 3 and 4 and the appearance of abnormal species at 26, 19 and 18 kDa, which were slightly more acidic than the major normal alpha A-crystallin polypeptide. The gamma-crystallin components, relatively unaffected at stage 4, were then lost rapidly as dense opacities ensued. By contrast with the water-soluble fraction, the normal day 9 urea-soluble fraction was deficient in gamma-crystallin polypeptides and enriched in anodic components whose relative electrophoretic mobilities were similar to those reported previously for phosphorylated bovine alpha A-crystallin and several cytoskeletal polypeptides. At stage 4 of the cataract, the modifications of normal alpha and beta-crystallin components in the urea-soluble fraction paralleled those in the water-soluble fraction, but the products seen were more numerous. In addition, the cytoskeletal proteins were no longer detectable. Substantial increases in lens Ca2+ that precede all of the above changes in lens polypeptide composition suggest that Ca(2+)-activated proteolysis may play a major role in development of BSO cataracts. PMID- 1623947 TI - Lens GSH depletion and electrolyte changes preceding cataracts induced by buthionine sulfoximine in suckling mice. AB - Cataracts were induced in suckling mice by multiple injections of L-buthionine S,R-sulfoximine (BSO), a specific inhibitor of GSH biosynthesis, starting on post natal day 7. The earliest visible lens aberrations began approximately 2 days after t(o), following 99% depletion of lens GSH. Cataract development then proceeded through four stages within less than 24 hr. Elevated Na+ and Ca+ and decreased K+ were first detected in pre-cataractous (stage 0) lenses. During stage 0, lens Na+ and K+ levels displayed a significant inverse correlation; by contrast, Ca2+ levels were poorly correlated with those of Na+. The initial increase in Na+ exceeded the decrease in K+. This suggested the presence of osmotic stress prior to cataract stage 1 (developing floriform). Increased lens hydration was first apparent in stage 1, coincident with a marked elevation of Ca2+, further increase in Na+ and decrease in K+. These trends persisted in the stage 2 cataract (completed floriform). Subsequent changes in lens hydration and cation content during cataract stages 3 (degenerate floriform) and 4 (amorphous translucent) suggested substantial influx of extracellular fluid into the affected lenses. The BSO cataract may represent a useful in vivo model to study the functions of GSH in maintaining normal lens cation balance and transparency. PMID- 1623948 TI - Mutant zeta-crystallin from guinea-pig hereditary cataracts has altered structural and enzymatic properties. PMID- 1623949 TI - A device for quantitative measurement of the opacity of small animal lenses: application to Xenopus laevis. PMID- 1623950 TI - Retinal degeneration in the pcd/pcd mutant mouse: accumulation of spherules in the interphotoreceptor space. AB - The Purkinje cell degeneration (pcd) mutant mouse rapidly loses cerebellar Purkinje cells and about 50% of its retinal photoreceptor cells at between 3 and 5 weeks of age, and thereafter slowly loses the remaining photoreceptor cells during the first year of life. An ultrastructural study of the developing photoreceptor cells of the pcd/pcd retina was undertaken using both transmission and scanning electron microscopy to characterize further the previously reported retinal vesicles associated with this mutation. Transmission electron microscopy (TEM) revealed an abundance of 'bead-like' vesicles or excrescences in the extracellular matrix surrounding the inner segment region at post-natal day (P) 25. The vesicles are membrane bound, amorphous in appearance and vary in size from 125 to 370 nm. Scanning electron microscopy suggests that the vesicles seen with TEM are actually spherules formed from outpocketing and pinching off of the plasma membrane in the mitochondria-rich region of the rod inner segment. At P25, the spherules are concentrated in the interphotoreceptor space at the level of rod inner segments; at P40, however, they are displaced from their origin and appear mostly at the level of rod outer segments and in the subretinal space. PMID- 1623951 TI - Early expression and localization of rhodopsin and interphotoreceptor retinoid binding protein (IRBP) in the developing fetal bovine retina. AB - Differentiation and maturation of the photoreceptor outer segments are key steps in the development of the visual system. Morphological studies presented here show that the cow and human are nearly identical in the timing of outer segment appearance during fetal development, implying that the bovine retina is a good model system for the final stages of human photoreceptor development. To study photoreceptor maturation, rhodopsin and interphotoreceptor retinoid-binding protein (IRBP) were quantified by ELISA in a developmentally staged series of fetal bovine retinas. In addition, their localization within these retinas was determined by immunogold electron microscopy. Rhodopsin, as detected by antibodies directed against either the N- or C-terminal portions of the molecule, is first found at about 5.5 months gestation. It is first detected on the plasma membrane of the immature cilia and on the earliest emergent outer segment membrane, even before organized disk membranes are apparent. In contrast, whereas rhodopsin levels and outer segments are nearly undetectable before 5 months gestation, IRBP accumulates to a significant level (4-5% of the adult) as early as 3 months gestation. Immunogold electron microscopy confirmed this finding, with localization of IRBP predominantly in the subretinal space. PMID- 1623952 TI - Structural alterations in retinal tissues from rats deficient in vitamin E and selenium and treated with hyperbaric oxygen. AB - Vitamin E and selenium play key roles in preventing in vitro lipid peroxidation and free radical damage to retinal tissues. In this research, we studied the effects of hyperbaric oxygen on retinal structure in rats fed diets deficient in vitamin E and/or selenium. We also correlated any alterations in retinal structure with previously measured alterations in electroretinograms (ERGs). Age matched rats were fed a basal diet deficient in both vitamin E and selenium (B diet), a basal diet supplemented with vitamin E alone (B+E diet), or selenium alone (B+Se diet), or with both micronutrients (B+E+Se). Half the rats in each group were treated (+HBO) with hyperbaric oxygen (100% O2 at 3 ATA for 1.5 per hr day, 5 days per week) and half were not (-HBO). We previously found that the rats fed the B diet for 6 weeks and treated with HBO for 4 weeks (B+HBO group) had diminished a-wave ERG amplitudes. At this time point all rats in the B group and half of the rats in the B+E+Se group were killed for the structural studies reported here. Surprisingly, we found no evidence of photoreceptor cell necrosis [i.e. a decreased thickness of the outer nuclear layer (ONL)] in retinas from rats in the B+HBO group despite the diminished amplitude of the a-wave which arises from this retinal layer. Quantitative structural analyses of retinas from rats in the B+HBO, B-HBO, B+E+Se-HBO and B+E+Se+HBO groups also failed to reveal any significant differences in the cell height of the retinal pigmented epithelium (nasal, central or temporal regions) or the number of mitochondria, phagosomas or inclusion bodies in the central retinal pigment epithelium (RPE). The inner nuclear layer (INL) thickness was, however, consistently decreased in all retinal regions for the rats in the B+HBO group. Our previous work also showed that only rats fed the B+Se diet for 17 weeks and treated with HBO for 15 weeks (B+Se+HBO group) showed diminished a-wave and b-wave ERG amplitudes. At this time point rats in the B+E+Se, B+E, and B+Se groups were killed for structural studies reported here. Only rats in the B+Se+HBO group showed a significantly decreased (about 20%) thickness of the central ONL. This evidence of photoreceptor cell necrosis correlated very well with our previous observation of diminished a- and b-wave amplitudes only in the B+Se+HBO group (at week 17).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1623953 TI - Effects of light and darkness on pH outside rod photoreceptors in the cat retina. AB - We recorded pH in the extracellular space surrounding rod photoreceptors in the dark-adapted eye of the cat and during illumination with double-barreled H(+) selective microelectrodes. A pH of 7.17 was recorded in the vitreous at the retinal surface of the dark-adapted eye and this became more alkaline during light adaptation. In dark adaptation, a pH close to 7.00 was recorded in a region of maximal acidity in the extracellular space surrounding rods in the outer nuclear layer (ONL). pH steeply alkalinized as the microelectrode was moved more distally towards the retinal pigment epithelium (RPE), and almost reached the pH of the arterial blood at the apical surface of the RPE. Illumination produced an intraretinal alkalinization that was largest (up to 0.2 pH units) in the ONL, maximal in amplitude at rod-saturating intensities, and that was sustained during steady background illumination. The light-evoked alkalinization was relatively slow in onset, having a time constant (1/e) of 64 sec, and took 8-12.5 min to return to the dark-adapted level after the offset of maintained illumination. These results show that acid production by cat rods is highest in the dark, reflecting a high rate of energy metabolism, and suggest that glycolysis is required to support the dark current. Illumination, by suppressing both glycolysis and respiration, alkalinizes the extracellular space surrounding rods. The substantial change in pH outside rods from dark to light could alter pH dependent properties of the interphotoreceptor matrix. PMID- 1623954 TI - Effects of systemic hypoxia on pH outside rod photoreceptors in the cat retina. AB - We studied the effect of systemic hypoxia on intraretinal pH in the intact cat eye using double-barreled H(+)-sensitive microelectrodes. Hypoxia in the dark further acidified the extracellular space surrounding rods in the distal retina and this effect was maximal in the outer nuclear layer (ONL). An acidification occurred in response to essentially any decrease in PaO2 below the normoxic level. Light-evoked alkalinizations in the ONL were larger in amplitude during hypoxia than in normoxia and this difference increased with the severity of hypoxia. Background illumination suppressed the hypoxic acidification of the ONL, completely inhibiting it at rod saturating intensities, at levels of hypoxia down to PaO2s of 40 mmHg. Systemic hyperoxia produced a small alkalinization in the ONL, and a reduction in the amplitude of the light-evoked alkalinizations. This suggests that systemic hyperoxia can partially suppress the ongoing glycolysis of dark-adapted rods. Changes in blood flow during hypoxia also altered intraretinal pH. Hypoxia led to an alkalinization in the choroid in both dark and light adaptation that spread into the distal retina. This alkalinization is most likely caused by the increase in CO2 removal that occurs as systemic blood pressure, and as a consequence, choriocapillaris blood flow increase during hypoxia. The alkalinization attenuated the acidification that was observed outside rods during hypoxia. There was also an alkalinization of the proximal portion of the retina, which spread into the vitreous. This alkalinization was attributed to the autoregulatory increase in blood flow that occurs in the retinal vessels during hypoxia. These findings provide further evidence for the hypothesis that the energy metabolism of dark-adapted rods is exquisitely sensitive to systemic hypoxia so that any small decrease in PaO2 increases rod glycolysis. Rod saturating illumination can completely suppress this increase in glycolysis for all but severe hypoxia. An increase in blood flow in the choriocapillaris during hypoxia appears to mitigate the effects of hypoxia on the distal retina. PMID- 1623955 TI - Effects of intravenous acetazolamide on retinal pH in the cat. AB - Double-barreled H(+)-selective microelectrodes were used to study the effect on intravenous acetazolamide on intraretinal pH in the cat. Acetazolamide (11.4-27.8 mg kg-1 intravenously) caused a rapid acidification of the subretinal space. This change in pH originated in the most distal portion of the subretinal space and could not be attributed to a change in pH or PCO2 of the arterial blood. Slow light-evoked alkalinizations in distal retina, attributable to a decrease in rod photoreceptor energy metabolism, were relatively unaltered by acetazolamide. This result indicated that acetazolamide had not crossed the blood-retinal barrier in sufficient amounts to change this response. In time, following intravenous perfusion of acetazolamide, continuous depth profiles of intraretinal pH showed an acidification of the entire retina and the vitreous also became more acidic. These results indicate that the rapid or primary effect of acetazolamide is an acidification of the distal portion of the subretinal space, which is thought to originate in a change in the transport of H+ or HCO3- by the retinal pigment epithelium. This is followed by an acidification of the entire retina and vitreous, presumably due to diffusion of acid from the distal retina, although there could be additional causes. PMID- 1623956 TI - Spectroscopic studies on the interaction of calf lens membranes with crystallins. AB - The interaction of crystallins with lens membranes and liposomes was studied by fluorescence and circular dichroism (CD) measurements. Two extrinsic fluorescence probes ANS (1-anilino-naphthalene-8-sulfonic acid) and DPH (1,6-diphenyl, 1,3,5 hexatriene) were used to detect the binding and to explore the binding site. The ANS fluorescence intensity is greater in membranes than in liposomes, but is reverse for DPH. Among alpha, beta and gamma-crystallins, only alpha c-crystallin decreased the ANS fluorescence intensity in membranes, indicating a binding between membranes and alpha c-crystallin. The binding site appears to be at the polar-apolar interface in membrane protein (MIP26) and alpha c-crystallin. Fluorescence polarization measurements show that lipid bilayer becomes less mobile with alpha c-crystallin binding. The change in the near UV CD due to the binding also indicates a decreased freedom of rotation of aromatic amino acid residues either in MIP26 or in alpha-crystallin. PMID- 1623957 TI - Fatty acid composition of phospholipids from chick neural retina during development. AB - The fatty acid composition of retina phospholipids from developing chicks was investigated to determine what changes, if any, occur in the relative levels of polyunsaturated fatty acids. Embryonic chicks were killed at 3-day intervals from day 6 through hatching (day 21), and at 1 week post-hatch. Fatty acids were prepared from retina phospholipids and were analysed by capillary gas-liquid chromatography. A comparison of the composition of yolk taken on day 6 with retinas isolated on that day revealed a much greater proportion of polyunsaturated fatty acids in the latter, suggesting an ability of the embryo to metabolize selectively unsaturated fatty acids at this early stage of development. Throughout the time course studied, saturated fatty acids constituted 50% of all fatty acids, most of which was due to palmitic acid (16:0; 33-41%). Among other saturated fatty acids, myristic acid (14:0) increased to maximal levels by day 18, then declined, while stearic acid (18:0) was minimal on day 12 and then increased. Polyunsaturated fatty acids varied between 14 and 23% of total fatty acids, depending on the developmental stage. One of the most remarkable changes in polyunsaturated fatty acids occurred in the levels of 22:4 (n-6). The proportion of this single fatty acid decreased from 9.4 to 2.4% between days 15 and 18. Relative levels of 22:5 (n-6) increased significantly between day 21 and 1 week post-hatch, from 1.1 to 3.2%. In this same time period, the proportion of 22:6 (n-3), the fatty acid known to be prominent in the outer segments of rod-dominant retinas, did not change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623958 TI - Pressures in the anterior ciliary arteries, choroidal veins and choriocapillaris. AB - A micropuncture technique was used to measure the pressure in the anterior ciliary arteries of monkeys as well as the pressures in the choroidal veins and in the choriocapillaris of rabbits. Monkeys were used to measure the pressure in one of the anterior ciliary arteries at three different points, First at a scleral 'well', and then at 2 and 5 mm from the same 'well'. It was found that the pressures recorded increased proportionally to the distance from the scleral 'well'. Afterwards the intraocular pressure (IOP) was increased stepwise and the arterial pressure was measured at each increment (from spontaneous IOP to 50 cmH2O). When compared, it was found that an increase in IOP was not followed by a statistically increased anterior ciliary artery pressure. The pressure in the choroidal veins and the choriocapillaris was measured in rabbits through a scleral window positioned between the two superior veins at about 4 mm from the nearest. The pressure recorded in the choroidal vein was found to be 3.3 +/- 0.4 cmH2O higher than the spontaneous IOP (20.3 +/- 1.6). However, when the IOP was increased stepwise it was found that this difference diminished as the value for the IOP neared the arterial pressure. Thus, the pressure gradient for flow from the intermediate-seized choroidal veins to the intraocular origin of the vortex veins is only a few cmH2O under normal conditions and is reduced at very high intraocular pressures at which the blood flow is markedly reduced or stopped.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623959 TI - Phospholipid composition of myeloid bodies from chick retinal pigment epithelium. AB - The phospholipid composition of a myeloid body (MB) enriched subcellular fraction of chick retinal pigment epithelium (RPE) was determined in order to further characterize the origin and functional significance of these lamellar membrane organelles. The major MB phospholipids found were phosphatidylcholine and phosphatidylethanolamine which represented 43% and 34% of the total MB lipids respectively. Sphingomyelin and phosphatidylinositol comprised the remaining detectable phospholipids. The fatty acyl chain composition of all detected phospholipids showed that the long-chain polyunsaturated fatty acids [arachidonic (20:4 n-6), docosapentaenoic (22:5 n-3) and docosahexaenoic (22:6 n-3)] account for greater than 45% of the fatty acids in MB membranes. This high proportion of long-chain polyunsaturated fatty acids in MBs is particularly striking when compared to the long-chain fatty acid composition of the photoreceptor outer segments from this predominantly cone retina which contains less than 25% long chain polyunsaturated fatty acids. The results from this study clearly demonstrate that MB lipids represent a significantly enriched pool of long-chain polyunsaturated fatty acids. PMID- 1623960 TI - Improving the safety of topically applied timolol in the pigmented rabbit through manipulation of formulation composition. AB - The objective of this study was to compare the efficiency of various formulations in maximizing the ratio of ocular to systemic absorption of topically applied timolol in the pigmented rabbit. Formulations of various pHs, tonicities, and concentrations of benzalkonium chloride, EDTA, poly(vinyl alcohol), poly(vinylpyrrolidone), hydroxypropylcellulose, and Na hyaluronate were tested. Ocular absorption was determined by monitoring the timolol concentration in various anterior segment tissues 30 min after instillation of timolol solution, while systemic absorption was determined by monitoring the time course of timolol concentration over 120 min. Timolol was assayed by reversed-phase HPLC. Lowering the solution tonicity to 80 mosmol kg-1 and incorporating polymers into the formulation were the only approaches that promised to improve the safety of topically applied timolol, since they afforded the desired increase in ocular absorption and reduction in systemic absorption. Lowering the solution pH to 6.4 and increasing the tonicity of the solution to 600 mosmol kg-1 reduced systemic absorption but caused either no change or a decrease in ocular absorption. Raising the solution pH to 8.4 and incorporating 0.025% benzalkonium chloride and 0.5% EDTA into the formulation led to an undesirable increase in systemic absorption although ocular absorption was also increased. In the final analysis, the net effect of formulation changes on the ratio of ocular to systemic absorption depended on the interplay of changes in solution drainage; permeability of the cornea, conjunctiva, and nasal mucosa; and fraction of drug in the preferentially absorbed form. PMID- 1623961 TI - Ageing and changes in protein conformation in the human lens: a Raman microspectroscopic study. AB - Using confocal Raman microspectroscopy with laser light of 660 nm the secondary and tertiary conformation of crystallins was studied in human lenses of varying age (20-75 years). Differences in cortical and nuclear proteins in individual lenses and among lenses of different age and differences between small equatorial opacities and adjacent clear sites were analysed using a difference spectrum approach. Intensity calibration allows assessment of local variations in protein content. The main findings and conclusions are as follows. (1) Irrespective of the age of the lens nuclear proteins proved to contain more aromatic amino acids, i.e. tryptophan, tyrosine and phenylalanine. This change most probably reflects differences in crystallin composition between nucleus and cortex as described in biochemical studies. (2) Changes in the amide bands indicate a more pronounced beta-sheet conformation of the nuclear proteins. Taking into account available biochemical evidence this most probably reflects a true post-translational change in the secondary conformation of the crystallins. (3) Cortical proteins in 'old' and 'young' lenses are largely identical indicating that ageing is not accompanied by gross alterations in the transcription/translation of the crystallin genes. (4) 'Old' and 'young' nuclear proteins deviate with respect to the amount of aromatic amino acids, being more abundant in 'young' nuclear proteins. (5) Proteins in small early opacities do not exhibit alterations in conformation. (6) A pronounced peak in the difference spectra in the region 1425 1435 cm-1 for nuclear proteins especially when compared with equatorial cortical proteins may be considered as evidence for the advanced photooxidation of tryptophan and/or deamidation of asparagine from superficial to deep regions of the lens. PMID- 1623962 TI - Temporal and regional production of 12(S)hydroxyeicosatetraenoic acid [12(S) HETE] in rat lens. AB - Enzymatic production of 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] from exogenous arachidonic acid (AA) was studied in the 9000 g supernatant fraction of either whole rat lens or the capsule-epithelium and cortex-nucleus regions with age (4-180 days). Whole rat lens 12(S)-HETE synthetic capacity measured either by RIA or HPLC was significantly decreased with lens growth. 12(S)-HETE production was highest in the 4-day-old rat lens, the earliest time point measured, and declined to background levels by 6 months of age. Regional studies demonstrated that the capsule-epithelium possessed a higher specific activity in comparison to the cortex-nucleus. However, lipoxygenase activity decreased significantly faster in the capsule-epithelium compared to the cortex-nucleus. The bulk of the 12 lipoxygenase activity was located in the cortex-nucleus due to the higher amount of tissue in the region. The elevated lipoxygenase activity in the neonate and its rapid decline with growth suggests that the enzyme may contribute in transforming the epithelial cells to fiber cells. PMID- 1623963 TI - Characterization and application of an in vitro detection system for studying the binding and phagocytosis of rod outer segments by retinal pigment epithelial cells. AB - Direct and indirect radioactivity and fluorescent assays have been developed to study the interaction of rod outer segments (ROS) with retinal pigment epithelial (RPE) cells. In the direct assays ROS labelled with 125I or fluorescein isothiocyanate (FITC) have been used to measure total phagocytosis, i.e. surface binding and ingestion. In the indirect assays RPE cells were first treated with unlabelled ROS or biotinylated ROS and subsequently probed with [125I]Rho 4D2 antirhodopsin antibody or [125I]streptavidin for radioactivity measurements or with the Rho 4D2 antibody and FITC-goat anti-mouse Ig or FITC-streptavidin for fluorescent counting. In these indirect methods the number of surface bound ROS were distinguished from the number of ingested ROS by comparative labelling of non-permeabilized and permeabilized ROS-treated RPE cells. Using these assays, we have studied the binding and ingestion of bovine ROS with cultured bovine RPE cells. As in the case of newborn cultured rat RPE cells [Hall and Abrams (1987) Exp. Eye Res. 45, 907-22], binding and ingestion of bovine ROS by bovine RPE cells was saturable with respect to ROS concentration and time. At 37 degrees C ROS binding reached a saturating concentration at 1 x 10(7) ROS per well; the number of bovine ROS ingested by bovine RPE cells, however, was less than the number of rat ROS ingested by rat RPE cells. When 1 x 10(7) ROS per well was used, maximal surface binding of bovine ROS to bovine RPE cells was obtained after 2-3 hr, whereas after an initial delay, ingestion rapidly increased to a maximum at 1-2 hr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623964 TI - Temporal regulation of six crystallin transcripts during mouse lens development. AB - Using the polymerase chain reaction (PCR) and RNA blot analysis, we have examined the differential expression patterns of the gamma-crystallins during lens development. Since only four of these genes had been previously characterized, the cDNAs for the remaining two genes, gamma C and gamma F, were isolated and sequenced. The steady-state mRNA profiles were then determined by RNA blot analysis of samples from embryonic stages to 180 days after birth, with gene specific probes for gamma A, gamma B, gamma C, and gamma D, and a common probe for gamma E and gamma F. Due to the paucity of mismatches between the gamma E and gamma F-crystallin genes, the PCR technique was exploited to determine their relative abundance. The data showed that while all six gamma-crystallin genes were expressed in the embryonic lens, they were differentially regulated during development. At early stages, the levels of gamma B and gamma C mRNAs were found to be relatively low in comparison to those for gamma A, gamma D, gamma E and gamma F. After 30-40 days, however, the levels of gamma A, gamma E, and gamma F mRNAs declined rapidly, and the gamma B, gamma C and gamma D transcripts became the major gamma-crystallin mRNA species. The utility of the PCR technique in studying the relative abundance of steady-state gamma-crystallin mRNAs was also investigated. PMID- 1623965 TI - Regional variations in electrolytes related to resistivity during bovine lens maturation. AB - Little is known regarding the behavior of ions in protein-rich cytoplasm characteristic of lens fiber cells. Resistivity is dependent upon the electrolyte concentration available to conduct an applied current and the mobility of these electrolytes. In the present study, the relative importance of these factors in the increasing cortico-nuclear resistivity gradient reported for both calf and bovine lens homogenates was analysed. Relative ion mobility for regions of the lens was determined by the calculation of the ratio of resistivity of lens homogenates to resistivity of aqueous solutions of freely mobile KCl at the same molarity. The increasing resistivity ratios in the calf cortex, transition zone and nucleus suggest an increasingly impaired ion mobility from the outer to the inner lens regions. PMID- 1623966 TI - The second human beta B2-crystallin gene is a pseudogene. AB - Comparison of the partial sequences of the human beta B2-1- and beta B2-2 crystallin genes with orthologous rat or calf sequences shows that the fourth exon sequence of the human beta B2-2 gene contains a one triplet deletion and a mutated splice acceptor site. No transcripts from the beta B2-2-crystallin gene could be detected in the human lens. These data suggest that the human beta B2-2 crystallin gene is a pseudogene. PMID- 1623967 TI - A reassessment of protein synthesis by lens nuclear fiber cells. PMID- 1623968 TI - The effect of 12(R)-hydroxyeicosatetraenoic acid on aqueous humor dynamics in the rabbit and cynomolgus monkey. PMID- 1623969 TI - Phospholipid distribution among bovine rod outer segment plasma membrane and disk membranes. PMID- 1623970 TI - Rapid PCR-based construction of specifically enriched libraries from small retina samples. PMID- 1623971 TI - Frontal units of the monkey coding the associative significance of visual and auditory stimuli. AB - Two monkeys were trained on both visual and auditory association tasks. Single unit activity of the frontal (prefrontal and post-arcuate premotor) cortex was recorded in these monkeys to investigate the convergence of visual and auditory inputs and to examine whether the frontal units are involved in coding the meaning (associative significance) of the stimulus, independent of its modality. A total of 289 units showed changes in firing rate after the cue presentation on the visual and/or auditory tasks and were examined on both modalities of tasks, 175 of them showing differential activity in relation to either the associative significance and/or physical properties of the visual and/or auditory cues. Of the 289 units, 136 (47.0%) were responsive only to the visual cue (76 of them showing cue-related differential activity), 13 units (4.5%) only to the auditory cue (6 of them showing cue-related differential activity) and the remaining 140 units (48.5%) to both modalities of cues (18 of them showing visual, 7 of them showing auditory and 68 showing both modalities of cue-related differential activity). Fifty of the 68 bimodal differential units showed changes in firing in relation to the associative significance of both modalities of cues independent of the cue's physical properties, and are considered to be involved in the crossmodal coding of the associative significance of the stimulus. The proportion of bimodal differential units was higher in the pre- and post-arcuate areas than in the principalis and inferior convexity areas of the frontal cortex. The results indicate that some frontal units participate in the crossmodal coding of the associative significance of the stimulus independent of its physical properties, and most frontal units play different roles depending on the modality of the stimulus. PMID- 1623972 TI - Statistical analysis of long-term potentiation of large excitatory postsynaptic potentials recorded in guinea pig hippocampal slices: binomial model. AB - Excitatory postsynaptic potentials (EPSPs) were recorded in guinea pig hippocampal slices (area CA1) from 15 neurons after stimulation of stratum radiatum (str. rad.) and stratum oriens. EPSP amplitudes increased in 8 neurones (10 post-tetanic regions) recorded 15 to 45 min after tetanic stimulation of str. rad. The increase was considered to represent long-term potentiation (LTP). Quantal analysis was performed by two methods assuming binomial statistics: the histogram method using deconvolution of noise and the variance method. According to both methods, LTP was associated with an increase in mean quantal content (m) which correlated with LTP magnitude. A statistically significant increase in quantal size (v) was found only by the histogram method and the increase was not correlated with LTP magnitude. A separate analysis of EPSPs with small LTP magnitude demonstrated that with the histogram method only v was increased but not m. A smaller increase in m for the pooled data of both methods did not correlate with LTP magnitude for this EPSP subset. The increase in m for the whole EPSP set corresponds to previous results on the quantal analysis of LTP in in vivo preparations and favours a presynaptic location of major mechanisms underlying LTP maintenance. The increase in v indicates the existence of another mechanism responsible for the maintenance of a small part of LTP. This mechanism might involve either pre- or postsynaptic changes or both. PMID- 1623973 TI - Quantal analysis of long-term potentiation of "minimal" excitatory postsynaptic potentials in guinea pig hippocampal slices: binomial approach. AB - "Minimal" excitatory postsynaptic potentials (EPSPs) were recorded from 13 neurones in area CA1 of guinea pig hippocampal slices after double-pulse stimulation of stratum radiatum (str. rad.) and stratum oriens (str. or.). Amplitudes of EPSPs significantly increased in 8 neurones 5 to 55 min after 9 tetanizations in str. rad.. The increase was considered to represent long-term potentiation (LTP). Altogether 26 EPSPs (42 post-tetanic regions) were statistically analysed by four methods of the quantum hypothesis assuming the binomial model of transmitter release: the deconvolution (histogram), the variance, the failures, and the combined (variance-failures) methods. The mean quantal content (m) significantly increased after LTP induction according to all methods used. Quantal size (v) also tended to increase but according to some methods, the increase was not statistically significant and it did not correlate with LTP magnitude. However, for an EPSP subset with a LTP magnitude of less than 1.55, the increase in v correlated with LTP magnitude, whereas the increase in m did not. The relative contribution of the increase in v to LTP magnitude was larger for cases with small LTP than for the whole EPSP set. In general, the increase in m corresponds to previous studies and favours the presynaptic location of major mechanisms of LTP maintenance, i.e. an increase in the average number of transmitter quanta released by each presynaptic volley. The post tetanic increase in v might reflect some additional mechanisms which presumably include an increase in the amount of transmitter in one quantum. PMID- 1623974 TI - Analysis of fluctuations of "minimal" excitatory postsynaptic potentials during long-term potentiation in guinea pig hippocampal slices. AB - In previous studies, quantal analysis assuming a simple binomial model has shown that long-term potentiation (LTP) is accompanied by an increase in both mean quantal content (m) and quantal size (v), whereby the increase in m predominates. In the present study, "compound" binomial distributions with variable probabilities were convolved with Gaussian distributions in computer experiments to simulate amplitude histograms of intracellular excitatory postsynaptic potentials (EPSPs). A deconvolution procedure assuming equal "quantal" separation (v) between discrete components, but without assuming binomial statistics, was applied to the simulated distributions to determine v. It was found that with a small ratio of standard deviation of noise to v (Sn/v less than 0.4), a reliable estimate of v can be obtained even for small samples (N = 100). When Sn/v was larger (0.4-0.6), approximate v estimates (within +/- 10-20% of the simulated v) could be obtained by averaging estimates from about 10 small samples (N = 100). "Minimal" EPSPs were recorded in area CA1 of guinea pig hippocampal slices. 37 EPSP amplitude samples of 9 neurones were measured before and up to 55 min after 10 tetanizations of stratum radiatum. In accordance with the previous data, the increase in v accounted for only about 10% of the average post-tetanic increase in EPSP amplitude and was not correlated with the latter. However, for an EPSP subset with small LTP magnitude, the increase in v accounted for an essential part of the LTP magnitude while the increase in m did not correlate with it. The results are in agreement with previous data obtained in the context of the simple binomial model and are interpreted as indicating primarily a presynaptic mechanism of LTP maintenance. The results suggest two types of synaptic mechanism of LTP maintenance related to the increases in m and v, respectively. The latter mechanism is saturated at about 10 to 30% increase in post-tetanic amplitude above the pre-tetanic EPSP amplitude. PMID- 1623975 TI - The frontal eye field provides the goal of saccadic eye movement. AB - Microstimulation of oculomotor regions in primate cortex normally evokes saccadic eye movements of stereotypic directions and amplitudes. The fixed-vector nature of the evoked movements is compatible with the creation of either an artificial retinal or motor error signal. However, when microstimulation is applied during an ongoing natural saccade, the starting eye position of the evoked movement differs from the eye position at stimulation onset (due to the latency of the evoked saccade). An analysis of the effect of this eye position discrepancy on the trajectory of the eventual evoked saccade can clarify the oculomotor role of the structure stimulated. The colliding saccade paradigm of microstimulation was used in the present study to investigate the type of signals conveyed by visual, visuomovement, and movement unit activities in the primate frontal eye field. Colliding saccades elicited from all sites were found to compensate for the portion of the initial movement occurring between stimulation and evoked movement onset, plus a portion of the initial movement occurring before stimulation. This finding suggests that activity in the frontal eye field encodes a retinotopic goal that is converted by a downstream structure into the vector of the eventual saccade. PMID- 1623976 TI - Responses of neurons in the caudal medullary raphe nuclei of the cat to stimulation of the vestibular nerve. AB - In the decerebrate cat, recordings were made from neurons in the caudal medullary raphe nuclei to determine if they responded to electrical stimulation of the vestibular nerve and thus might participate in vestibulosympathetic reflexes. Many of these cells projected to the upper thoracic spinal cord. The majority (20/28) of raphespinal neurons with conduction velocities between 1 and 4 m/s received vestibular inputs; 13 of the 20 were inhibited, and 7 were excited. Since many raphespinal neurons with similar slow conduction velocities are involved in the control of sympathetic outflow, as well as in other functions, these cells could potentially relay vestibular signals to sympathetic preganglionic neurons. The onset latency of the vestibular effects was long (median of 15 ms), indicating the inputs were polysynaptic. In addition, 34 of 42 raphespinal neurons with more rapid conduction velocities (6-78 m/s) also received long-latency (median of 10 ms) labyrinthine inputs; 26 were excited and 8 were inhibited. Although little is known about these rapidly-conducting cells, they do not appear to be involved in autonomic control, suggesting that the function of vestibular inputs to raphe neurons is not limited to production of vestibulosympathetic reflexes. One hypothesis is that raphe neurons are also involved in modulating the gain of vestibulocollic and vestibulospinal reflexes; this possibility remains to be tested. PMID- 1623977 TI - Vocalizations in the cat: behavioral methodology and spectrographic analysis. AB - Attempts to understand the neural mechanisms underlying mammalian vocal behaviors, including speech, require study of the neural activity and anatomy of vocalization-controlling brain structures. Such studies necessitate the application of invasive neurobiological techniques in animal models. In the current study, cats are used in the development of an animal model of vocal tract control. The animals are instrumentally conditioned to vocalize for food reward. Acquisition of this task can occur within a few minutes, although additional training generally is required to solidly establish the behavior and to train subjects to produce consistently high rates of vocalization for prolonged periods of time. Following training, animals can generally sustain a rate of two calls per minute for a period of over two hours. Optimal task performance is partly dependent on motivation level. Although there is considerable variation between animals, the vocalizations produced have an average duration of 600 ms and a fundamental frequency of around 500 Hz. In addition, during a typical vocalization, there are dynamic variations of about 150 Hz for fundamental frequency and 17 dB for sound intensity. These variations provide opportunities for relating neural and muscular activity to different aspects of the vocal behavior they control. Based on a number of considerations, the model and techniques discussed here probably are most applicable to studying the neurobiology of sub-cortical nuclei subserving vocal control. Similar mechanisms might well be present in other species, including humans. Thus, data obtained from study of this model may be applicable to understanding the processes underlying vocal tract control during human speech. PMID- 1623978 TI - Factors influencing neural activity in parabrachial regions during cat vocalizations. AB - The parabrachial nucleus in mammals is intimately connected with other vocalization controlling brainstem structures. It, along with ventromedially adjacent structures, also has been identified as the pneumotaxic center, and as such shows strong respiratory related activity in the anesthetized cat. The current study examines the neuronal activity in cat parabrachial regions during production of instrumentally conditioned vocalizations. Most of the units in our sample show considerable activity during periods between vocalizations. For many units, firing rate fluctuates during the respiratory cycle, although apparently not as strongly as reported in the decerebrate cat. Also, there is often strong phasic activity during periods where animals are licking to ingest their food rewards. During the peri-vocalization period, various neural activity patterns can be recorded. Most common is an activity increase during the vocalization itself. Moreover, in some units, this activity increase has an auditory component. A smaller number of units show other activity patterns, including a suppression of activity during vocalization and activity increases preceding the vocalization. Overall, our results suggest that the parabrachial region's involvement in vocal control is quite complex, involving convergence of respiratory, acoustic, vocalization-related, and perhaps somatosensory influences. PMID- 1623979 TI - Multiple representation in the nucleus lateralis of the cerebellum: an electrophysiologic study in the rat. AB - The motor organization of the nucleus lateralis (NL) of the rat's cerebellum was investigated by observing the motor effects of electrical microstimulations of the NL. The movements evoked by the NL mainly concerned forelimb and head segments. Only in a few cases were movements of hindlimb segments evoked. Motor effects were obtained according to a precise topographical pattern. This pattern delimited functional zones, or representations, within the NL, each zone being specifically related to a particular segment of the body. A few body segments were activated from single zones only (single representation) whereas some other body segments could be activated from different zones of the NL. Among them, the axio-proximal body segments were activated in a similar way from all sites (multiple representation) whereas the distal body segments were differently activated from the various representation zones (specific representation). The multiple and specific representations were distributed between the 3 cytoarchitectonic subregions of the NL (NLm, DLH and slp) in such a way that the body segments were usually represented only once in each individual NL subregion. Each NL subregion included sets of representations concerning body segments characterized by a topographical continuity (e.g. the different segments of the forelimb in both DLH and slp). Thus, the individual NL subregions may bring into play coordinate plurisegmental muscular activities of the limbs and/or of the head. The NLm controls movements of all the segments of the head and those of axio-proximal segments of both limbs. The DLH particularly controls movements of the head, including both the proximal (neck) and the oral regions. To a lesser degree, DLH controls movements of the various segments of the forelimb, including synchronous flexion of all the digits. The slp is specifically involved in the control of motor activities of: i) the proximal segment of the head (rotation of the neck) as well as its distal segments (displacement of individual vibrissae, rotation of the ear pinna) and ii) the various segments of the forelimb including individual digits. Functionally, the proximal segments would be concerned in the spatial displacement of the limbs or of the head whereas the distal segments would be involved in the realization of precise and discrete movements related to specific functions of the distal segments concerned. The 3 subregions of the NL may be concerned in different motor functions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1623980 TI - Direct retinal projections of the "non-image forming" system to the hypothalamus, anterodorsal thalamus and basal telencephalon of mink (Mustela vison) brain. AB - The retinal projections of the "non-image forming" system to the hypothalamus, anterodorsal thalamus and basal telencephalon were visualized in adult mink using the anterograde transport of cholera toxin conjugated to horseradish peroxidase injected intraocularly. A major and nearly symmetrical bilateral input of labeled retinal fibers to the suprachiasmatic nuclei was observed. A dense innervation was also evident in both paraventricular nuclei, and in the anterior, lateral and mediobasal hypothalamus on the side contralateral to the injection. Two projections leaving the optic tract at the level of the lateral hypothalamus or after crossing the geniculate body entered the anterior thalamus and ran in a ventro-dorsal or a caudorostral direction before terminating in the stria terminalis. Fibers were also observed in the horizontal limb of the diagonal band of Broca. These observations are compared to those in other mammalian species and discussed according to their possible implication in photoperiodic signal processing. PMID- 1623981 TI - Changing patterns of binocular visual connections in the intertectal system during development of the frog, Xenopus laevis. III. Modifications following early eye rotation. AB - In the frog, Xenopus laevis, a system of intertectal connections underlies the visual projection from an eye to its ipsilateral tectal lobe and is involved in the topographic representation of binocular visual space. Rotation of one eye in early life may be followed by a radical rearrangement of the connections in this system. The modified pattern which later emerges is that which keeps the visual projection through the ipsilateral eye in topographic registration with the direct visual projection from the contralateral eye to the same tectal lobe. This plasticity requires visual experience. In this paper we describe the time-course and sequence of events by which this plasticity is effected. Following rotation of one eye in larval animals or in animals undergoing metamorphic climax, the earliest evidence of intertectal modification was found 3-4 weeks after metamorphosis. With increasing intervals after metamorphosis an increasing proportion of animals displayed modified intertectal systems. At intermediate intervals many animals showed partial modifications, which were interpreted as transitional stages in the modification process. Analysis of these transitional stages indicated that the sequence of events involved in the elaboration of a modified intertectal system following the experimental alteration of eye alignment exhibits features in common with rearrangements of the system that occur during normal development in response to growth-related alterations in eye alignment. PMID- 1623982 TI - Characterisation of a human glioblastoma cell line (LI) expressing hypothalamic and pituitary hormones. AB - The human glioblastoma cell line LI showed morphological features typical of its neuroectodermal origin. Cells were positive by immunofluorescence to GFAP, MHC class II, and L1 determinants. Cytogenetic analysis showed the presence of a modal chromosome number of 63, ranging from 58 to 69 chromosomes (DNA index was 1.6). Northern blot analysis demonstrated the presence of mRNA transcripts specific for transglutaminase C (type II or "tissue"), growth-hormone releasing hormone (GHRH), insulin-like growth factor II (IGF-II), and proopiomelanocortin (POMC). The GHRH mRNA was present in two different sizes, one similar to the normal hypothalamic species of 0.75 kb, whilst the second species was a large transcript of approximately 10 kb size. Treatment with 5 microM retinoic acid or 5 mM alpha-difluoromethylornithine for 5 days sharply reduced the growth rate and also induced modulation of the ultrastructure and antigenic profile. This cell line may be useful to study glial differentiation and the relationship of GHRH, IGF-II and POMC expression with differentiation in neuroectodermal tumours. PMID- 1623983 TI - Characteristics of "anti" saccades in man. AB - Four subjects - all made large numbers of Express saccades in the normal gap task - were instructed to make saccades in the direction opposite to the side where a visual stimulus appeared ("anti" task). Gap and overlap trials were used. Saccadic reaction time (SRT), velocity and amplitude of the corresponding eye movements were analysed and compared to those of saccades made in the normal task. The velocity of "anti saccades" was found to be slightly (up to 15%) but significantly slower in two subjects. The distributions of SRTs in normal gap tasks show a small group of anticipatory saccades (with SRT below 80 ms and slower velocities) followed by a group of saccades with fast reaction times between 80 ms and 120 ms (Express saccades) followed by another large group ranging up to 180 ms (regular saccades). In the gap anti task there are anticipatory saccades and saccades with SRTs above 100 ms; Express saccades are missing. The distribution of SRTs obtained in the overlap anti task was unimodal with a mean value of 231 ms as compared to 216 ms in the normal task. The introduction of the gap therefore clearly decreases the reaction times of the anti saccades. Control experiments show that the delay of anti saccades is not due to an interhemispheric transfer time but must be attributed to the saccade generating system taking more time to program a saccade to a position where no visual stimulus appears. These data are discussed as providing further evidence for the existence of a reflex-like pathway connecting the retina to the oculomotor nuclei mediating the Express saccade. PMID- 1623984 TI - Eye position signals in human saccadic processing. AB - 1. We studied saccades to briefly flashed targets in 8 human subjects. The target flash occurred (i) during smooth pursuit ("ramp-flash"), (ii) just before a saccade to another target ("step-flash"), or (iii) during steady fixation ("flash only"). All lights were extinguished after the target flash so that smooth pursuit or saccadic eye movements occurred during the interval of complete darkness between the target flash and the saccade to it. We compared these saccades to those made without intervening eye movement (flash only), and quantified the extent to which the saccadic system compensated for the change in eye position that occurred during the dark interval. 2. Saccades to control flashes were reasonably accurate (mean gain 0.87) and consistent. Compensation for the intervening eye movement in the ramp-flash and step-flash paradigms was highly variable from trial to trial. On average, subjects compensated for 27% of the intervening pursuit eye movement on ramp-flash trials and for 58% of intervening saccadic movement on step-flash trials. 3. Multiple regression analysis showed that the variability did not depend on factors such as variations in underlying saccadic gain, response latency, timing of stimuli or size of the required response. We conclude that this variability is intrinsic to saccadic responses that require the use of an eye position signal. 4. These results show that an eye position signal is available to the saccadic system but that this signal has low fidelity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623985 TI - Changes of cortical activity when executing learned motor sequences. AB - Fifteen right-handed subjects performed a learned sequence of four movements (flex index finger, extend hand, extend index finger, flex hand) either with their left or their right hand. The sequence of movements had to be continuously repeated for 20 s (period of execution). In the beginning of each period of execution large negative DC potentials were recorded in positions located above the mesial fronto-central cortex (Cz) and the sensorimotor hand areas of either hemisphere (C3 and C4). In contrast, DC potentials were absent in Cz at the end of the period of execution. In recordings from a position above the sensorimotor hand area contralateral to the performing side, negative DC potentials declined to some extent during task execution but were still present at the end of the period. Variations of both the amplitude and topography of negative cortical DC potentials during task-execution indicate changes of both the size and pattern of cortical activity. These findings were consistently found at both the beginning and end of the experiment. Motor performance as quantified by movement times and inter-onset latencies of movements showed no change, either during the periods of execution or when comparing the beginning of the experiment with the end. Conclusions are: (1) the execution of a learned motor sequence task cannot be associated with a particular size and pattern of cortical activity. (2) A pronounced decline of neural activity in the mesial, fronto-central area constitutes the predominant feature of the changes of cortical activity during the period of execution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1623986 TI - A frontal cortical potential associated with saccades in humans. AB - We describe a frontal EEG potential which begins 25-35 ms before intentional saccadic eye movement. It consists of a 15-20 muvolt monophasic positive waveform with peak during or just after movement, and returns to EEG baseline 150-200 ms after its onset. The waveform is largest at a midline position just anterior to FZ (10-20 system), is independent of visual input such as fixation guides, and is not related to saccade direction or amplitude. The potential is difficult to observe in some subjects and is independent of the "pre-saccadic spike potential". It may be related to the discharge of single cortical neurons that signal the initiation of saccadic movements, but not their exact metrics; a possible generator is the supplementary eye fields of the dorsomedial prefrontal cortex. PMID- 1623987 TI - Lowered cutaneous sensitivity to nonpainful electrical stimulation during isometric exercise in humans. AB - The effect of isometric exercise on cutaneous sensitivity to nonpainful electric stimulation was studied in human subjects. The exercises consisted of brief (duration: 1-10 s) palmar flexions of the hand or foot against varying loads (10 30% of the maximal force). A visual "go" cue was used to indicate the start and end of the exercise. Isometric hand exercise produced a load-dependent increase of electrotactile thresholds of the fingers. The threshold elevation was rapidly attenuated with prolonged duration of the exercise. The hand exercise-induced threshold elevation was of equal magnitude in the glabrous and hairy skin of the fingers. Thresholds were not changed for the hand contralateral to the exercising hand. Passive static pressure of the hand did not produce threshold changes, whereas activation of afferent inhibition by a vibrotactile stimulus (100 Hz, 0.1 mm) did produce a significant threshold elevation. Exercise-induced threshold elevation was also significant immediately prior to the EMG response of the arm but not at the time of the visual "go" signal, or before it. The threshold increase found during the EMG response was not significantly stronger than that found prior to the EMG response. These results suggest that isometric exercise load-dependently produces a phasic, rapidly attenuating increase in cutaneous tactile thresholds in the exercising limb but not multisegmentally. Corollary efferent barrage from motor to sensory structures of the brain could be underlying the threshold changes produced by isometric exercise, whereas afferent inhibitory mechanisms seem to have only a minor role. PMID- 1623988 TI - Miniature excitatory postsynaptic potentials in embryonic motoneurons grown in slice cultures of spinal cord, dorsal root ganglia and skeletal muscle. AB - Miniature excitatory postsynaptic potentials (mEPSPs) were recorded in motoneurons grown in organotypic cocultures of embryonic rat spinal cord, dorsal root ganglia and muscle in the presence of TTX. The motoneurons were electrically compact with a mean electrotonic length of 0.6. Spontaneous EPSPs were found in most of these motoneurons. With TTX the large EPSPs disappeared, whereas in more than half of the experiments mEPSPs persisted with a range in size of 1 to 4 mV (mean: 2.1 mV), probably originating from the spontaneous release of single vesicles. The net inward charge transfer at the soma ranged from 0.12 to 0.34 pC. The mEPSPs were heterogeneous in size even within pools of potentials that were homogeneous in shape. They had similar shapes and amplitudes as the smallest spontaneous unitary EPSPs mediated by presynaptic impulses, suggesting that for the smallest afferents not more than one vesicle was released per afferent impulse. Both the miniature and the TTX-sensitive EPSPs were readily blocked by the glutamate antagonist DNQX. PMID- 1623989 TI - In vitro study of central respiratory-like activity of the fetal rat. AB - A fetal rat brain stem-spinal cord in vitro preparation (15-20 days) which retains for several hours respiratory-like discharges on cervical and cranial ventral roots has been developed for analysing fetal central respiratory activity. Two different patterns of easily distinguishable rhythmic activity were recorded. The first, of spinal origin, appeared every 2-10 min as long bursts of potentials (3-30 s) on cervical, but not hypoglossal, roots. The second pattern corresponded to brief bursts (1 s) of potentials occurring on both cervical and hypoglossal roots at a frequency ranging from 3-4 cycles min-1. The second type of activity was likely to be respiratory since it originated from the medulla, and behaved similarly to the respiratory activity recorded in vitro from newborn rats. The fetal respiratory-like activity was never observed at day 15, appeared at day 16 in 30% of the preparations with fluctuating frequency and amplitude bursts, and stabilised at day 20 where it was usually present and resembled newborn rat respiratory activity: its frequency was stable but was reduced by withdrawal of CO2 and pH stimuli and modulated by a pontine noradrenergic influence. This fetal preparation offers many advantages for studying the ontogeny of the central respiratory activity because of the background knowledge available on the adult and newborn rat respiratory centers and the possibility of performing electrophysiological, morphological and pharmacological fetal studies directly at the central level without any feedback from the periphery. PMID- 1623990 TI - Myomectomy for fertility enhancement and preservation. AB - OBJECTIVE: To review, evaluate, and synthesize current published reports assessing the value of abdominal myomectomy in infertile women and those desiring to preserve fertility potential. DATA IDENTIFICATION: Major studies dealing with myomectomy were identified through Medline Searches. STUDY SELECTION: Those papers reporting the results of myomectomy, factors influencing them, and potential future innovations were obtained. RESULTS: More than half of women not previously pregnant and undergoing myomectomy to preserve childbearing capacity for treatment of recurrent pregnancy wastage or previous infertility conceive. The long duration of infertility before surgery, absence of other factors to explain their not conceiving, and short time interval subsequent to surgery in which conception occurs suggests myomectomy has value in treatment of patients with leiomyomata and otherwise unexplained infertility. The operation carries acceptable risk. Approximately 25% of women undergoing myomectomy have recurrent leiomyomata, but most recurrences are sufficiently delayed to allow adequate opportunity for conception. CONCLUSIONS: Abdominal myomectomy is an appropriate alternative to hysterectomy for most women who wish to preserve childbearing potential or enhance it. For the future, myomectomy by endoscopic techniques may hold similar potential. PMID- 1623991 TI - Human embryos produce transforming growth factors alpha activity and insulin-like growth factors II. AB - OBJECTIVE: To assess whether growth factors are produced by early human embryos in culture. DESIGN: We studied various growth factors in the culture media of human embryos (n = 6) cultured from days 3 to 8 after fertilization. MAIN OUTCOME MEASURES: Four growth factors were measured: Insulin growth factors I and II (IGF I and IGF-II), epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) activity. RESULTS: Nonconditioned INRA Menezo B2 (Biomerieux, S.A., Paris, France) culture medium contained significant levels of TGF alpha activity (5.2 ng/mL) and low levels of IGF-I (1.02 ng/mL) and IGF-II (2.8 ng/mL), whereas EGF was below detection of our assay. With human embryo, the culture media contained lower TGF alpha activity on days 3 and 4 after fertilization (2.5 ng/mL and 2.8 ng/mL, P less than 0.05). From days 5 to 8 after fertilization, a significant increase in TGF alpha activity and IGF-II was detected (TGF alpha activity: day 5: 3.7 ng/mL; day 6: 4.4 ng/mL; day 7: 6.4 ng/mL; day 8: 8.4 ng/mL) (IGF-II: day 5: 3.4 ng/mL; day 6: 3.1 ng/mL; day 7: 4.1 ng/mL; day 8: 4.2 ng/mL). Epidermal growth factor was undetectable, and IGF-I did not vary significantly. CONCLUSION: Transforming growth factor alpha activity and IGF-II are produced by human embryos in culture at a time when they could play a role in morula to blastocyst transformation. PMID- 1623992 TI - Specific binding sites for insulin in the human myometrium and leiomyomas of the uterus. AB - OBJECTIVE: To investigate whether there are increased binding sites for insulin in the leiomyomas of the uterus. STUDY DESIGN: Samples of myomas and myometrium were obtained from seven patients with myomas at the time of hysterectomy. Binding studies were performed with [125I] insulin. RESULTS: The percent total binding of [125I] insulin in the myomal tissues (mean +/- SE 20.7% +/- 2.3%/100 micrograms protein) was significantly higher (P less than 0.01) than that in the myometrium (14.7% +/- 1.3%/100 micrograms protein). Scatchard analysis revealed that the increase in binding is because of increase in receptor affinity. CONCLUSIONS: There is increased binding of insulin in the myomas because of increase in receptor affinity. This could increase the sensitivity of the biological response of the myomal cells to insulin. PMID- 1623993 TI - Nonclassical 3 beta-hydroxysteroid dehydrogenase deficiency: a review of our experience with 25 female patients. AB - OBJECTIVE: To report 15 new menarcheal women affected with nonclassical 3 beta hydroxysteroid dehydrogenase deficiency (nonclassical 3 beta-HSD) and evaluation of glucocorticoid therapy in treated patients. DESIGN: Diagnosis of these new patients using a standard adrenocorticotropin test. Effects of glucocorticoid therapy on clinical hormonal and sonographic features of each patient are appreciated for periods varying between 4 months and 7 1/2 years. SETTING: All at The New York Hospital-Cornell Medical Center. The Pediatric Endocrinology Ambulatory Service; the Children's Clinical Research Center Core Laboratories; and the Department of Radiology. PATIENTS, PARTICIPANTS: Fifteen menarcheal women (14 to 30 years of age) newly diagnosed and 10 women previously diagnosed were evaluated for symptoms of hyperandrogenism and/or irregular menses. MAIN OUTCOME MEASURE(S): Positive effect of glucocorticoid therapy on signs and symptoms, hormonal levels, and ovarian imaging. RESULTS: Polycystic ovarian syndrome is noted in approximately half the cases. Glucocorticoid treatment greater than 3 months duration results in a reversal of symptoms in most cases. PMID- 1623994 TI - Evaluation of a 1-year levonorgestrel-releasing contraceptive implant: side effects, release rates, and biodegradability. AB - OBJECTIVE: To determine the release rates, effects on ovulation, and side effects of two lengths of a biodegradable, subdermal contraceptive implant containing levonorgestrel in a caprolactone capsule. DESIGN: Phase II randomized clinical trial. SETTING: Public family planning clinic at an urban general hospital. PARTICIPANTS: Forty-eight healthy, parous, ovulating volunteers. INTERVENTION: Subjects were randomly assigned either a 2.5- or a 4.0-cm contraceptive capsule that was worn under the skin of the upper arm for 1 year if not removed earlier for other reasons. MAIN OUTCOME MEASURES: Serum concentrations of levonorgestrel, progesterone, estradiol, and lipoproteins were measured as were metabolic parameters. Vaginal bleeding and other side effects were recorded. After implant removal, remaining levonorgestrel, capsule viscosity, and molecular weight were measured. RESULTS: The 4-cm implant provided serum concentrations of levonorgestrel ranging from 0.65 ng/mL shortly after insertion to 0.20 ng/mL at 12 months, but the 2.5-cm implant resulted in levels too low for contraception. The 4-cm implant suppressed ovulation in approximately 80% of cycles over 1 year of use, but the 2.5-cm implant failed to suppress ovulation. The implants were rapidly and easily inserted and removed. They retained structural integrity through 1 year of use. Of 48 subjects, 32 had abnormal bleeding patterns; the mean number of days of bleeding per month was 7 with 23 days between episodes. Women using capronor maintained normal metabolic parameters except that low density lipoprotein decreased slightly. CONCLUSIONS: The 4.0-cm implant is a promising contraceptive. There were no important metabolic effects, but there were bothersome minor side effects typical of progestin-only contraception. PMID- 1623995 TI - Psychological improvement in infertile women after behavioral treatment: a replication. AB - OBJECTIVE: To replicate previously reported psychological improvements in infertile women attending a group behavioral treatment program. DESIGN: Psychological and demographic data were collected before entering and again upon completion of a behavioral medicine program on a second cohort of patients. SETTING: The program was offered in the Division of Behavioral Medicine, an outpatient clinic of the Department of Medicine at New England Deaconess Hospital. All patients were receiving care from infertility specialists not affiliated with this hospital. PATIENTS: Fifty two self-referred women receiving medical treatment for infertility attended the program. INTERVENTION: A 10-week group behavioral treatment program. MAIN OUTCOME MEASURES: Three validated psychological instruments. RESULTS: Psychological improvement was statistically significant (Profile of Mood States Tension/Anxiety: P less than 0.0001; Depression/Dejection: P less than 0.0122; Vigor/Activity: P less than 0.0431; Confusion/Bewilderment: P less than 0.0057; Spielberger Anger Expression: P less than 0.0013; Spielberger State Anxiety: P less than 0.0037, and Trait Anxiety: P less than 0.0001). CONCLUSIONS: Behavioral treatment is associated with significant decreases in negative psychological symptoms. PMID- 1623996 TI - The ratio of androstenedione:11 beta-hydroxyandrostenedione is an important marker of adrenal androgen excess in women. AB - OBJECTIVE: To determine if the ratio of serum androstenedione (A):11 beta hydroxyandrostenedione (OHA) would be helpful in differentiating adrenal from ovarian hyperandrogenism. DESIGN/SETTING: Prospective study of outpatients being evaluated for hyperandrogenism. PATIENTS/PARTICIPANTS: Normal women (n = 27), those with hyperandrogenic chronic anovulation (n = 25), and 7 with adult onset of congenital adrenal hyperplasia (CAH) because of 21-hydroxylase deficiency. INTERVENTIONS: Fasting serum between 8:00 A.M. and 9:00 A.M. Patients with hyperandrogenic chronic anovulation and CAH received dexamethasone (DEX) 2 mg for 7 days. MAIN OUTCOME MEASURES: Serum testosterone (T), unbound T, dehydroepiandrosterone sulfate (DHEAS), A, and 11 beta-OHA by radioimmunoassay. RESULTS: Serum 11 beta-OHA and DHEAS were elevated in 52% and 40% of patients with hyperandrogenic chronic anovulation and in 7 of 7 and 1 of 7 patients with CAH. The ratio of A:11 beta-OHA was significantly higher (P less than 0.05) in hyperandrogenic chronic anovulation and significantly lower (P less than 0.05) in CAH compared with controls. Serum A:11 beta-OHA correlated with T (r = 0.58, P less than 0.05). The ratios of A:11 beta-OHA were similar and significantly lower in CAH and hyperandrogenic chronic anovulation patients who were DEX sensitive compared with those who were not DEX sensitive. The ratio correlated with the percentage suppression of T, unbound T, and A after DEX (P less than 0.01). There were no differences with measurements of DHEAS and 11 beta-OHA. Using the mean ratio of controls (1.3) as a cutoff value, the sensitivity of the A:11 beta-OHA in detecting adrenal hyperandrogenism, as assessed by DEX sensitivity, was 100%, the specificity was 84%, and the predictive value was 67%. CONCLUSIONS: The ratio of A:11 beta-OHA appears to be an excellent marker for identifying patients with adrenal hyperandrogenism and CAH. PMID- 1623997 TI - Transport in vitro fertilization--a novel scheme for community-based treatment. AB - OBJECTIVE: To provide an inexpensive and extensive in vitro fertilization (IVF) service for the Mersey Region, United Kingdom. DESIGN: Twenty-four transport IVF patients treated in two district general hospitals using the central university laboratory as co-ordination point for treatment schedule and embryology. Outcomes were compared with 26 control patients treated in the central unit. SETTING: Royal Liverpool University Hospital, a central IVF unit, and two district general hospitals in the Mersey Region. PATIENTS: Fifty patients under 35 years of age with irreversible tubal damage selected and treated by IVF, half in the central unit and the other half in two district general hospitals. MAIN OUTCOME MEASURES: Pregnancy rate (PR) in the different centers. RESULTS: A PR of 42.3% per cycle in the peripheral hospitals compared with 30.7% per cycle in the central unit. CONCLUSION: Transport IVF is an inexpensive and feasible alternative to standard IVF in a central unit for patients without access to central units. PMID- 1623998 TI - Subtle rise in serum progesterone during the follicular phase as a predictor of the outcome of in vitro fertilization. AB - OBJECTIVE: To investigate the effects of subtle rises in serum progesterone (P) during the follicular phase on the outcome of in vitro fertilization and embryo transfer (IVF-ET). DESIGN, PATIENTS: One hundred one patients underwent IVF-ET for 170 cycles and were stimulated with a combination of clomiphene citrate and human menopausal gonadotropin. Based on their hormonal data, we divided the patients into two groups: those who had a cycle with an increase in serum P concentration (1.0 to 2.0 ng/mL) that was not associated with a pituitary LH release (subtle P rise) and those who had a cycle without any increase in serum P concentration (no P rise). MAIN OUTCOME MEASURES: The daily serum estradiol (E2) concentration and the results of IVF-ET (number of developed and collected oocytes, rates of mature oocytes, fertilization, and pregnancy) were compared between the two groups. RESULTS: Subtle P rises were observed in 31.7% (32/101) of the patients and 20.5% (36/170) of the cycles evaluated during the IVF-ET programs. A significantly higher serum E2 concentration (P less than 0.001) and a greater number of developed and collected oocytes (P less than 0.001 and P less than 0.05, respectively) also were observed in those cycles with a subtle P rise. The rates of mature oocyte formation and fertilization were significantly lower in cycles with a subtle P rise (P less than 0.001 and P less than 0.05, respectively). A lower pregnancy rate was observed in cycles with a subtle P rise, and all 12 ongoing pregnancies occurred only in cycles with a no P rise. CONCLUSION: These results suggest that the development of an increased number of follicles may not necessarily improve the outcome of IVF-ET and that the measurement of serum P may be a better predictor for successful pregnancy. PMID- 1623999 TI - Understanding the current status of oocyte donation in the United States: what's really going on out there? PMID- 1624000 TI - A prospective, randomized study of pregnancy rates after transuterotubal and intrauterine insemination. AB - OBJECTIVE: To assess the relative efficacy, in terms of clinical pregnancy rates (PRs), of transuterotubal insemination versus the more traditional intrauterine insemination (IUI) procedure. DESIGN: Prospective, randomized, cross-over. SETTING: University-affiliated tertiary care center. PATIENTS: One hundred sixty infertile patients underwent 414 inseminations with or without controlled ovarian hyperstimulation. INTERVENTIONS: All patients were randomized in their initial cycle to transuterotubal insemination or IUI then crossed-over in subsequent cycles (n = 191 total cycles of transuterotubal insemination and n = 223 total cycles of IUI). Transuterotubal insemination was performed initially with ultrasound guidance, and then a tactile technique was used for the last 6 months of the study. MAIN OUTCOME MEASURES: Clinical PRs and complications after both insemination methods. RESULTS: The clinical PR per treatment cycle was 7% (13/191) after transuterotubal insemination and 7% (16/223) after IUI. The overall PR per patient was 18% (29/160). The incidence of ectopic pregnancy was 1 in 191 for transuterotubal insemination cycles and 0 in 223 for IUI cycles. Other complications included 3 vasovagal episodes with transuterotubal insemination and 1 with IUI. There was no clinical evidence of tubal infection, trauma, or perforation in either group. CONCLUSION: Transuterotubal insemination did not appear to be associated with a higher PR when compared with IUI in this study. The potential for increased risk from complications related to the more invasive tubal technique does not appear to justify its use presently. PMID- 1624001 TI - Internal quality control of semen analysis. AB - OBJECTIVE: To test a scheme for quality control of semen analysis. DESIGN: The reproducibility of assessment of sperm concentration, motility, and morphology was obtained for the same sample measured by different technicians (between or intertechnician variation) and for different samples assessed by each technician with time (within or intratechnician variation). SETTING: Andrology Laboratory. PATIENTS: Semen samples were analyzed from all patients attending the clinic. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Within technician and between technician coefficients of variation for concentration, motility, and morphology. RESULTS: When 100 sperm were routinely assessed, both intratechnician variation, as assessed from the precision of duplicate measurements, and intertechnician variation revealed hyperbolic curves with increasing variation at low percentages (less than 20) of motile or morphological forms. When these low values were excluded, mean intratechnician variations were 5.0%, 8.4%, and 2.8% for concentration, motility, and morphology, respectively, and mean intertechnician variations were, respectively, 6.1%, 5.6%, and 5.6%. Similar mean intertechnician variation for morphology was obtained for repeated assessment of prestained (7.3%) or presmeared (5.9%) slides. The use of cryopreserved semen to monitor longitudinal changes in the technicians' assessments revealed variations of 8.1% to 12% in concentration and 9.7% to 14% in motility. Computing the monthly means for sperm concentration, motility, and morphology over a 4.5-year period revealed a marked reduction in percentage of normal morphological forms, unrelated to the sperm count or mean age of the men attending the clinic. This was shown to be a result of a shift in the assessment by technicians. CONCLUSIONS: Quality control is necessary and possible in an andrology clinic. PMID- 1624002 TI - Spermatozoal characteristics from fresh and frozen donor semen and their correlation with fertility outcome after intrauterine insemination. AB - OBJECTIVE: To determine if conventional sperm parameters, specific characteristics of sperm motion determined by computer-aided semen analysis (CASA), sperm penetration assay (SPA), and/or spontaneous acrosome reaction assay could best predict fertility outcome after intrauterine insemination (IUI) from frozen donor sperm. DESIGN: A retrospective analysis of 2,245 cycles of therapeutic donor IUIs were initially studied; 1,147 cycles that met selection criteria were used in this report. SETTING: A university-based assisted reproductive technology center. PATIENTS, PARTICIPANTS: All IUIs were performed on women with documented patency of at least one fallopian tube, ovulatory cycles, and who did not receive human menopausal gonadotropins. Sperm donors had to be used for at least four different recipients (mean of 15) and at least 14 different cycles of insemination (mean of 41). INTERVENTIONS: None. MAIN OUTCOME MEASURE: Pregnancy. RESULTS: Statistical comparisons were made between donors of different relative fertility by using the Mann-Whitney test, Spearman's rank correlation, and multiple regression analysis. These analyses demonstrated that the most significant predictors of the fertility of frozen-thawed donor sperm were curvilinear velocity, straight line velocity, and the total number of motile sperm inseminated. The number of sperm with spontaneous acrosome reactions negatively correlated with fertility outcome, and SPA provided no predictive value. CONCLUSIONS: Our study supports the hypothesis that the study of sperm motion characteristics using CASA after thawing and washing of cryopreserved sperm is a better predictor of fertile outcome after IUI than analysis of fresh semen. PMID- 1624003 TI - Failure to fertilize in vitro in couples with male factor infertility: what next? AB - OBJECTIVE: To assess the predictive value of a failure to fertilize in vitro in couples with sperm abnormalities on future fertility. DESIGN: Retrospective file review. SETTING: In vitro fertilization and embryo transfer (IVF-ET) program in the Sheba Medical Center during the years 1983 to 1990. PATIENTS: Seventy-six couples with sperm abnormalities who had at least one IVF cycle during which fertilization did not occur. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Occurrence of fertilization, percentage of fertilization, and pregnancies in additional IVF-ET cycles. RESULTS: Of 44 couples who underwent an additional IVF attempt with husband's sperm, 36 (81.2%) fertilized, with a mean fertilization rate of 47.7% +/- 26.6%. Of 17 couples who failed twice, 11 attempted IVF again with husband's sperm and 7 fertilized, with a median rate of 33%. A higher sperm concentration was found on the cycles during which fertilization occurred. Men with single parameter abnormalities did not fertilize better than those with two or three defective parameters. CONCLUSIONS: Failure to fertilize in vitro in couples with male factor infertility does not seem to predict future fertilization in IVF. At least two cycles of IVF should be tried before reverting to other options such as insemination by donor sperm or gamete micromanipulation. PMID- 1624004 TI - Early pregnancy wastage: the role of repetitive human chorionic gonadotropin supplementation during the first 8 weeks of gestation. AB - OBJECTIVE: To determine if repetitive administration of hCG causes decreased pregnancy wastage rates in patients who are at a high risk of luteal inadequacy. DESIGN: Ovulation induction using human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) or clomiphene citrate (CC) is associated with luteal phase defects that may cause increased pregnancy wastage. An increased risk of abortion exists also in pregnancies in patients with previous repeated miscarriage, women older than 37 years, and various causes of infertility such as hyperprolactinemia. Because the presumed common denominator to the increased rate of pregnancy wastage in all these cases is luteal dysfunction, repetitive hCG administration, 2,500 U two times weekly, was carried out between the 4th and 8th week of gestation in 249 cases of ovulation induction and/or previous abortions, whereas 198 gestations served as controls (no hCG administration). RESULTS: In the hCG treatment group, 43 ended in miscarriage (17.3%) versus 97 abortions in the control group (49%, P less than 0.01). In 160 cases of hMG/hCG generated gestations, 94 received hCG and 66 did not. The pregnancy wastage rates were 21.3% and 42.4%, respectively (P less than 0.05). In 144 cases of CC/hCG-induced pregnancies, 95 received hCG and 49 served as controls. The respective abortion rates were 15.8% and 44.8% (P less than 0.01). The remaining 143 spontaneous conceptions occurred in infertile patients with previous repeated abortions. In 60 of these conceptions, hCG was administered during the first 4 weeks of gestation and 83 cases served as control. The pregnancy wastage rates were 13.3% versus 56.6%, respectively (P less than 0.001). CONCLUSION: Repetitive administration of hCG during the early gestation in cases that are at high risk of luteal inadequacy may significantly decrease the pregnancy wastage rate. PMID- 1624005 TI - Ultrastructure of human sperm in men with congenital absence of the vas deferens: clinical implications. AB - OBJECTIVE: To determine the ultrastructural features of epididymal and vasa efferentia sperm in men with congenital absence of the vas deferens. DESIGN: Prospective. SETTING: University of California Irvine Center for Reproductive Health. PATIENTS: Thirteen men with surgical diagnosis of congenital absence of the vas deferens undergoing epididymal and vasa efferentia aspiration for assisted reproductive technology procedures. RESULTS: The morphological quality and the integrity of the spermatozoa aspirated from the extratesticular segment of the rete testis, the vasa efferentia, and the caput epididymis were always markedly superior to those of sperm aspirated from the corpus and cauda epididymis, where the vast majority, if not all, were degenerating or frankly necrotic. The aspirates obtained from the distal segments of the epididymis also contained large numbers of sperm-laden macrophages; these were instead absent or exceptional in the fluids aspirated from the pre-epididymal portions of the excurrent pathways and from the caput of the epididymis. CONCLUSIONS: This study demonstrates that the ultrastructural morphology of spermatozoa obtained by aspiration from the rete testis, vasa efferentia, and caput epididymis of individuals with congenital absence of the vas deferens is indistinguishable from that of spermatozoa in the semen. PMID- 1624006 TI - Improved fertilization rate in an in vitro fertilization program by egg yolk treated sperm. AB - High fertilization and PRs have been achieved by using thawed donor sperm cryopreserved with medium containing EY. The aim of our study was to examine the possible effect of EY on the fertilizing capacity of fresh sperm in an IVF program. Preincubation of spermatozoa in EY for 2 hours at room temperature significantly improved fertilization (P less than 0.001) in couples who had low fertilization rates in previous cycles, whereas no effect was found concerning couples with high fertilization rates. PMID- 1624007 TI - White blood cell immunization and anticardiolipin antibody levels in women with recurrent miscarriages. AB - To determine whether WBC immunization stimulates production of anticardiolipin antibodies, anticardiolipin antibodies were measured before and 6 weeks after WBC immunization. Twenty-four non-pregnant women, who had had recurrent miscarriages for which a definitive cause could not be determined, were immunized with their partner's WBC. No significant differences in levels of anticardiolipin antibodies were detected between paired samples of sera obtained before and 6 weeks after WBC immunization. White cell immunization in nonpregnant women did not stimulate production of anticardiolipin antibodies. PMID- 1624008 TI - Concurrent hyperprolactinemia and sperm autoimmunity in a man with secondary infertility. AB - A case is presented of secondary infertility due to the concurrence of sperm autoimmunity and hyperprolactinemia. Treatment of his hyperprolactinemia with bromocriptine did not improve his fertility; however, concurrent treatment of both conditions resulted in improved semen quality, conception, and the birth of a healthy baby girl. PMID- 1624009 TI - Recurrence of myomas after myomectomy in women pretreated with leuprolide acetate depot or placebo. AB - The recurrence of myomas and myoma-related symptoms was evaluated in women participating in a randomized, double-blind, P-controlled study of the efficacy of LA depot before myomectomy. After 27 to 38 months of follow-up, the recurrence of myomas was found to be greater when at least four myomas were resected. Myoma recurrence was not associated with pretreatment or preoperative uterine volume, resected myoma mass, or preoperative medical therapy. PMID- 1624010 TI - The effect of varicocelectomy on testicular volume in 89 infertile adult males with varicoceles. AB - The presence of a varicocele has been associated with reduced testicular volumes both in the adult and pediatric patient populations. An increase in testicular volume after varicocelectomy, however, has been documented only in the latter group and then only in the ipsilateral testicle. We present our experience with 89 infertile male patients with varicoceles who underwent operative repair. An increase in testicular volume was observed in 72 of the 89 patients, with the right side showing a greater increase, regardless of whether bilateral or unilateral left varicoceles were present preoperatively. No greater increase in testicular volume was noted among the patients who went on to achieve a pregnancy with their spouses. In addition, the age of the patient did not influence the observed change in testicular volume. No correlation between varicocele grade and pregnancy nor between improvement in semen parameters and improvement in testicular volume could be demonstrated. PMID- 1624011 TI - Successful clinical application of laser for micromanipulation in an in vitro fertilization program. AB - This is a report of our preliminary experience with assisted hatching by laser with a case of an ongoing twin pregnancy. We used an erbium laser to create a 20 to 30-micrometer opening in the zona pellucida of human embryos to facilitate the embryonic hatching after the embryo transfer. Our report proves that it is possible to obtain a pregnancy using a simple and quick laser method instead of mechanical or chemical procedures within the scope of micromanipulation. PMID- 1624012 TI - Early diagnosis of ovarian torsion by color Doppler ultrasonography. AB - Ovarian torsion is often difficult to diagnose because of the nonspecific nature of the clinical findings. We report on the use of color Doppler ultrasonography in diagnosing early ovarian torsion. This technique provides a highly specific finding, the absence of blood flow to the ovary, that greatly facilitates the diagnosis of ovarian torsion. PMID- 1624013 TI - Ovarian failure and G-proteins--do we really need to know how they work? PMID- 1624014 TI - A simpler technique for reduction of uterine septum. PMID- 1624015 TI - Visual diagnosis of endometriosis--reliability? PMID- 1624016 TI - Reliability of the visual diagnosis of ovarian endometriosis? PMID- 1624017 TI - Value of sperm filtration? PMID- 1624018 TI - Defective oocytes: a new subgroup of unexplained infertility. AB - OBJECTIVE: To define a new category of unexplained infertility and its potential treatment. DESIGN: Normal infertile couples underwent prospectively, cross fertilization attempts in which the wife's oocytes were inseminated by the husband and donor semen. After recurrent failure of fertilization, cross insemination of donor oocytes was attempted with the husband sperm. SETTING: In vitro fertilization unit at a teaching hospital. PATIENTS: Three couples who were diagnosed as suffering of unexplained infertility and treated by in vitro fertilization (IVF). RESULTS: The female partner of these couples produced morphologically normal oocytes that were demonstrated to be functionally defective and failed to fertilize in vitro with both husband and donor sperm. Donated oocytes inseminated by the husband's sperm were fertilized in all patients, demonstrating the normal fertilizing ability of the husbands' semen. One patient conceived and delivered after an oocyte donation. CONCLUSIONS: Conclusive diagnosis of defective oocytes as a cause of infertility may be made only after IVF and oocyte donation. PMID- 1624019 TI - Superovulation with human menopausal gonadotropins in the treatment of infertility associated with minimal or mild endometriosis: a controlled randomized study. AB - OBJECTIVE: To determine the efficacy of superovulation with buserelin acetate, human menopausal gonadotropins (hMG), and human chorionic gonadotropin (hCG) in the treatment of infertility associated with minimal or mild endometriosis. DESIGN: Prospective, randomized, controlled study. SUBJECTS: Forty-nine infertile women with a laparoscopic diagnosis of endometriosis stage I (n = 29) or II (n = 20) according to the revised American Fertility Society classification, randomly assigned to three superovulation cycles (n = 24) or 6 months' expectant management (n = 25). MAIN OUTCOME MEASURES: Cycle fecundity rates and cumulative pregnancy rates (CPR) in the two groups. RESULTS: Nine pregnancies were obtained in the superovulation-treated patients and six in the nontreated ones. The cycle fecundity rates and CPR were 0.15% and 37.4% after three superovulation cycles and 0.045% and 24% after 6 months of expectant management (P less than 0.05 and P = not significant, respectively). The women who did not achieve a pregnancy after three cycles of superovulation were followed for a total of 50 months during which no therapy was given. One pregnancy started in this period (cycle fecundity rate = 0.020). One spontaneous abortion occurred in each group. Three treated patients had multiple pregnancies, and four had ovarian hyperstimulation syndrome. CONCLUSION: Superovulation seems to be associated with a better cycle fecundity rate but not a better CPR than expectant management in infertile women with endometriosis stages I and II. The efficacy and side effects of this therapeutic approach should be evaluated in larger series. PMID- 1624020 TI - Ovarian responses to menopausal gonadotropins in groups of patients with differing basal growth hormone levels. AB - OBJECTIVE: To investigate the relationship between endogenous serum levels of human growth hormone (hGH) and ovarian response to human menopausal gonadotropins (hMG). DESIGN: Retrospective analysis of patient response to hMG. SETTING: Center for assisted reproductive technology. PATIENTS: Eighty women who had undergone controlled ovarian hyperstimulation with hMG. Basal levels of hGH in sera from 40 of these patients were less than 5.0 microIU/mL (low hGH), values for the remaining 40 were greater than 5.0 microIU/mL (high hGH). Levels of hGH in day 2 sera were analyzed against numbers of oocytes recovered in an additional 182 patients. MAIN OUTCOME MEASURES: Serum estradiol (E2) levels and numbers of oocytes recovered at oocyte pick-up. RESULTS: Average (+/- SE) levels of hGH in sera of high-hGH and low-hGH patients were 10.2 +/- 0.6 and 2.47 +/- 0.3 microIU/mL, respectively (P less than 0.05). Respective peripheral levels of insulin-like growth factor-I were 105.3 +/- 2.9 and 97.2 +/- 2.8 ng/mL. Levels of E2 in serum of high-hGH patients exceeded respective (P less than 0.05) low-hGH values throughout folliculogenesis, and more oocytes were recovered from high-hGH patients (8.1 +/- 0.9 versus 4.7 +/- 0.5 for low-hGH patients; P less than 0.05). Serum progesterone values did not differ. Higher day 2 hGH levels were associated with higher numbers of oocytes recovered after controlled ovarian hyperstimulation. CONCLUSIONS: The present findings indicate that endogenous hGH may augment gonadotropins during follicle recruitment and during multiple folliculogenesis in women. The phase of maximum ovarian sensitivity to hGH/gonadotropin synergism and the nature of synergism remain unclear. PMID- 1624021 TI - Polycystic ovaries in patients with hypogonadotropic hypogonadism: similarity of ovarian response to gonadotropin stimulation in patients with polycystic ovarian syndrome. AB - OBJECTIVE: To characterize the ovarian response in patients with isolated hypogonadotropic hypogonadism with ultrasound (US) findings of polycystic ovaries (PCO). DESIGN: Twenty-seven treatment cycles in patients with hypogonadotropic hypogonadism and US findings of normal ovaries were compared with 31 cycles in patients with hypogonadotropic hypogonadism and US-diagnosed PCO. Forty-one cycles in the hypogonadotropic hypogonadism and US-diagnosed PCO were compared with 59 cycles of patients with polycystic ovarian syndrome (PCOS) to examine pattern of response after ovulation induction. SETTING: Specialist Reproductive Endocrine Unit. PATIENTS, PARTICIPANTS: Twenty hypogonadotropic patients in whom 10 had US findings of PCO and 13 patients with PCOS. MAIN OUTCOME MEASURE: Serum estradiol (E2) concentration, number of leading follicles on US, cancellation, and pregnancy rate. RESULTS: Hypogonadotropic patients with US-diagnosed PCO had higher baseline ovarian volume (P less than 0.02) compared with patients with hypogonadotropic hypogonadism with normal ovaries. After ovarian stimulation, a higher mean serum E2 concentration (P less than 0.001), endometrial thickness (P less than 0.001), and increased number of leading follicles (P less than 0.0001) were found in hypogonadotropic patients with US-diagnosed PCO, compared with hypogonadotropic patients with US findings of normal ovaries. Patients with PCOS had a higher serum E2 concentration (P less than 0.008), although they were treated for fewer days (P less than 0.0001) and with fewer ampules of gonadotropin (P less than 0.001) compared with patients with hypogonadotropic hypogonadism with US-diagnosed PCO. CONCLUSIONS: We have characterized a group of hypogonadotropic patients with US findings of PCO, in which the ovarian response to ovulation induction was similar to patients with PCOS. The results have practical and theoretical implications for the etiology and treatment of patients with PCO. PMID- 1624022 TI - Prediction and prevention of ovarian hyperstimulation by monitoring endogenous luteinizing hormone release during purified follicle-stimulating hormone therapy. AB - OBJECTIVE: To elucidate whether early detection of premature luteinizing hormone (LH) release can be useful for prediction and prevention of ovarian hyperstimulation during purified follicle-stimulating hormone (FSH) therapy. DESIGN: Retrospective and prospective study. PATIENTS: Infertile women with polycystic ovarian syndrome. MAIN OUTCOME MEASURES: Correlation between rate of endogenous LH release and incidence of excessive ovarian enlargement. In the prospective study, LH was measured by fluorometric enzyme immunoassay to obtain real-time concentration. Maximal ovarian diameter by ultrasonography. RESULTS: The rate of excessive ovarian enlargement (greater than or equal to 60 mm) in cycles that were treated by a daily administration of purified FSH and accompanied by premature LH release was 83.3%. This rate was significantly higher than that in cycles without premature LH release (24.1%, P less than 0.001). Interruption of FSH administration or alternate day FSH administration in cycles with premature LH release reduced the rate of ovarian enlargement to 45.5% (P less than 0.05). CONCLUSION: Early detection of premature LH release is useful for prediction of ovarian hyperstimulation. Ovarian hyperstimulation can be reduced by modulating the dose of FSH and the interval of administration in cycles with premature LH release. PMID- 1624024 TI - Distribution of follicle-stimulating hormone and luteinizing hormone isoforms in sera from women with primary ovarian failure compared with that of normal reproductive and postmenopausal women. AB - OBJECTIVE: To demonstrate if molecular heterogeneity of gonadotropins correlates with the type of primary gonadal failure. DESIGN AND METHODS: Aliquots of sera from women with hypogonadism were subjected to gel filtration chromatography to be assayed for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by the use of radioimmunoassay. Molecular weight (MW) of isoforms was calculated on a calibration curve obtained with molecular markers. The molecular variants were characterized on the basis of elution volume, MW, and partition coefficient. RESULTS: Chromatographic profile of sera from four women with natural menopause exhibited two FSH peaks of immunoreactivity and a heavier LH isoform. This pattern was different from that obtained in sera from women of reproductive age who presented a single peak that eluted after the corresponding standard. In six cases of idiopathic premature menopause and three more with gonadotropin resistant ovary, the chromatographic profile showed a marked and remarkable molecular heterogeneity, particularly LH, and this was more apparent in women with resistant ovary. CONCLUSIONS: Our investigation confirms the relationship between the gonadotropin heterogeneity with the gonadal failure. The duration of the ovarian failure may influence the molecular proportion of gonadotropins and the predominance of heavier MW isohormones. PMID- 1624023 TI - Pulsatile secretion of gonadotropins and prolactin during the follicular and luteal phases of the menstrual cycle: analysis of instantaneous secretion rate and secretory concomitance. AB - OBJECTIVE: To characterize the pulsatile secretions of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) during the menstrual cycle and to statistically evaluate their secretory concomitance. DESIGN: Pulsatility study performed during the midfollicular and midluteal phases of a same menstrual cycle, blood samples being collected every 10 minutes for 6 hours. SETTING: Participants investigated in the Division of Endocrinology, University Hospital. PARTICIPANTS: Nine healthy women (22 to 38 years) with regular menstrual cycles. MAIN OUTCOME MEASURES: Plasma LH, FSH, and PRL values were analyzed as raw and deconvoluted data, and the specific (nonrandom) secretory concomitance was evaluated statistically. RESULTS: The pulsatile secretion of LH was confirmed, and that of FSH and PRL was clearly established during both phases of the cycle by characterization of peak frequency, period, and amplitude. A specific secretory concomitance was assessed between LH and FSH in the follicular but not the luteal phase, and a tight concomitance between LH and PRL was demonstrated during both phases. CONCLUSIONS: These results are supportive of significant pulsatile secretions of the three hormones during the menstrual cycle, and they are demonstrative of a definite copulsatility of these hormones, suggestive of common regulatory factors in the complex temporal patterns of gonadotropin and PRL secretions along the cycle. PMID- 1624025 TI - Efficacy of a low-dose leuprolide acetate depot in the treatment of uterine leiomyomata in Japanese women. AB - OBJECTIVE: To compare the efficacy of two different doses, 1.88 mg and 3.75 mg, of a monthly depot injection of a gonadotropin-releasing hormone agonist (GnRH-a) in the treatment of uterine leiomyomata. DESIGN: A prospective randomized study. SETTING: Hospital department of gynecology and obstetrics. PATIENTS: Forty-one premenopausal Japanese women, 25 to 53 years of age, with uterine leiomyomata. INTERVENTIONS: Depot type of GnRH-a, leuprolide acetate (LA) 1.88 mg or 3.75 mg was administered subcutaneously every 4 weeks for 24 weeks. MAIN OUTCOME MEASURES: Efficacy of treatment was assessed in terms of uterine volume, serum levels of estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and adverse symptoms during treatment. RESULTS: In both groups, a significant reduction in uterine volume, 52% in 1.88 mg group and 47% in 3.75 mg group, was obtained at week 24, with near maximal reduction (41%, 45%) apparent by 12 weeks. No significant difference was observed between the groups in percent uterine volume reduction at each treatment week. Both groups showed significant and equal suppression of serum levels of E2, LH, and FSH. In addition, the incidence of adverse symptoms was not significantly different between the two groups. CONCLUSIONS: Monthly injection of 1.88 mg or 3.75 mg LA depot has equivalent treatment efficacy in reducing uterine volume. Twelve weeks of treatment is enough to obtain near maximal reduction. PMID- 1624026 TI - Clinical history and outcome of 59 patients with idiopathic hyperprolactinemia. AB - OBJECTIVE: To investigate the clinical course of hyperprolactinemia without demonstrable cause. DESIGN: Prospective study of all patients with idiopathic hyperprolactinemia first seen between 1974 and 1985. SETTING: Outpatient Department of University Hospital. PATIENTS: Fifty-nine patients followed for 6 to 190 months (median 78 months). Medical treatment given only in case of anovulatory infertility or hypogonadism. OUTCOME MEASURES: Development of pituitary (micro)prolactinoma, prolactin (PRL) levels, and clinical signs of menstrual dysfunction. RESULTS: With exception of one woman in whom it probably had been missed by hypocycloidal tomography, no demonstrable prolactinoma developed. Prolactin levels rose in two patients, one using oral contraceptives and the other with prolactinoma. At the end of follow-up, 15 of 16 patients using a dopaminergic drug had a normal cycle; 13 had normal final PRL levels. From the 43 patients off medication, 28 (66%) had normal PRL levels and 23 (54%) had a normal cycle. There were no significant differences between women who had and had not been pregnant. Dopaminergic medication had no appreciable influence on the course of the disease. CONCLUSION: In idiopathic hyperprolactinemia, progression to pituitary prolactinoma seldom, if ever, occurs. There is a high tendency to spontaneous cure, and pregnancy or medication have no apparent effect. Frequent pituitary imaging was found to be not necessary in our patient population. It may best be reserved for situations in which the PRL level in symptomatic hyperprolactinemia is inconsistent with pituitary imaging results. PMID- 1624027 TI - On the nature of serum prolactin in two patients with macroprolactinemia. AB - OBJECTIVE: To further characterize the high molecular weight (MW) forms of prolactin (PRL) present in patients with macroprolactinemia. DESIGN: Case reports with laboratory investigations. SETTING: Academic medical centers. PATIENTS: Two patients with macroprolactinemia. INTERVENTIONS: Measurements of PRL concentrations before and after chromatographic separations. RESULTS: The majority of serum PRL had an estimated MW of at least 669 kd in the first patient and approximately 171 kd in the second. During a pregnancy, a new form of PRL (MW 291 kd) appeared in the first patient's serum and persisted for at least 3 years. Immunoprecipitation and polyacrylamide gel electrophoresis under reducing and denaturing conditions revealed that the largest form of PRL (MW 669 kd) was composed mostly of 25 kd glycosylated PRL; intermediate forms (171 kd and 291 kd) were composed of roughly equal portions of 25 kd glycosylated PRL and 23 kd nonglycosylated PRL, whereas "little" PRL in these patients was composed primarily of 23 kd nonglycosylated PRL. Injection of the first patient's serum into rats demonstrated that the human PRL (hPRL) immunoreactivity was cleared from the serum more slowly than the PRL from sera containing predominantly little hPRL; after stimulation with thyrotropin-releasing hormone in the second patient, serum PRL concentrations decayed more slowly than observed in normal subjects. CONCLUSIONS: Large forms of serum PRL are at least partially glycosylated. These large forms are heterogeneous, both within and among patients. Delayed clearance may account for increased serum PRL concentrations in patients with macroprolactinemia. PMID- 1624028 TI - A comparison of the reproductive outcome between women with a unicornuate uterus and women with a didelphic uterus. AB - OBJECTIVE: To compare the reproductive performance of women with a unicornuate uterus with the reproductive performance of women with a didelphic uterus. DESIGN: Retrospective. SETTING: Reproductive endocrinology service of a tertiary referral hospital. MAIN OUTCOME MEASURES: The proportion of pregnancies resulting in spontaneous abortion, preterm delivery, term delivery, and living children was determined for each group. RESULTS: Twenty-nine women with a unicornuate uterus and 25 women with a didelphic uterus were identified. Twenty women with a unicornuate uterus produced a total of 40 pregnancies, whereas 13 women with a didelphic uterus produced a total of 28 pregnancies. The 33% spontaneous abortion rate in the unicornuate group was not significantly different from the 23% rate in the didelphic group. The proportion of pregnancies resulting in preterm delivery, term delivery, and living children was similar in both groups. CONCLUSIONS: The reproductive performance of women with a unicornuate uterus is similar to the performance of women with a didelphic uterus. PMID- 1624029 TI - Transvaginal ultrasonography in the diagnosis of diffuse adenomyosis. AB - OBJECTIVE: To evaluate the diagnostic capability of transvaginal ultrasonography in detecting diffuse adenomyosis. DESIGN: We compared the preoperative transvaginal ultrasound (US) findings and the pathological findings of the surgical specimen in a series of women who underwent hysterectomy for menorrhagia. PATIENTS: Forty-three women (mean [+/- SD] age of 46 +/- 5) with recurrent menorrhagia and enlarged uterus, without evidence of uterine leiomyomas at abdominal US and of endometrial disease at vabra curettage. SETTING: Tertiary care center, university medical school. MAIN OUTCOME MEASURES: Sensitivity, specificity, predictive positive and negative values of transvaginal US in the diagnosis of diffuse adenomyosis. RESULTS: The sonographer diagnosed adenomyosis in 22 patients, whereas the pathologist found adenomyosis in 20 women, confirming the US findings in 16 cases and making an ex novo diagnosis in 4. The sensitivity of transvaginal US was 80%, the specificity 74%, the predictive value of a normal test 81%, and that of an abnormal test 73%. CONCLUSIONS: Transvaginal US seems to represent a real advance in the preoperative diagnosis of diffuse adenomyosis. PMID- 1624030 TI - Transvaginal intratubal methotrexate treatment of ectopic pregnancy. AB - OBJECTIVE: To evaluate the efficacy of transvaginal intratubal methotrexate (MTX) treatment of tubal ectopic pregnancy (EP). SETTING: Outpatient setting in University Hospital. PATIENTS: Forty women with early EP and rising serum beta human chorionic gonadotropin (beta-hCG) levels. INTERVENTION: Transvaginal intratubal administration of MTX (1 mg/kg body weight). MAIN OUTCOME MEASURES: Success was defined as declining serum beta-hCG to undetectable levels, no tubal dilatation on ultrasound examination, and no further intervention was required. RESULTS: Treatment was associated with a 70% success rate. No difference was found in the success rate between women with an embryo (76.9%) and those with no embryo in their fallopian tubes (66.7%). The initial serum beta-hCG levels were also not different between patients who were successfully treated and those who failed to respond to the treatment. Despite declining serum beta-hCG levels, tubal rupture occurred in two patients. CONCLUSIONS: Treatment of EP by transvaginal MTX administration is associated with a 70% success rate. This is independent of the presence of an embryo or the initial serum beta-hCG levels. Rupture of EP can still occur despite low and declining serum beta-hCG levels. PMID- 1624031 TI - The neonatal eye. PMID- 1624032 TI - Recent progress on the mechanisms of embryonic lens formation. AB - Formation of the lens during embryonic development depends on tissue interactions as shown clearly both from teratological data and from extensive experimental analysis. Recent work has, however, altered our view of the importance of particular tissue interactions for lens formation. While earlier work emphasises the role of the optic vesicle in lens induction, more recent studies argue that lens-inducing signals important for determination act before optic vesicle formation. Evidence is given for a four stage model in which ectoderm first becomes competent to respond to lens inducers. It then receives inductive signals, at least in part emanating from the anterior neural plate, so that it gains a lens-forming bias and subsequently becomes specified for lens formation. Complete lens differentiation does require signals from the optic vesicle, and in addition an inhibitory signal from head neural crest may suppress any residual lens-forming bias in head ectoderm adjacent to the lens. PMID- 1624033 TI - Cellular organisation of the optic nerve and the implications for optic neuritis. AB - Opportunities for studying growth, degeneration and repair in the central nervous system have altered over the last decade with the development of techniques for culturing neurones and glia and the availability of immunological or molecular markers that identify separate lineages and their progeny. Much pioneering work has been carried out in the rodent optic nerve but the principles that emerge are representative for other parts of the nervous system; development of neurones and glia may differ substantially in rats and man, so that assumptions must be made in extrapolating from properties of the rat optic nerve to diseases of the human central nervous system. PMID- 1624034 TI - Early visual development: differential functioning of parvocellular and magnocellular pathways. PMID- 1624035 TI - A morphological comparison of foveal development in man and monkey. AB - The fovea can first be identified in both monkey and human retina at 26-30% gestation as a region containing all adult retinal layers and only cone photoreceptors. A shallow foveal pit and cone outer segments appear by 63-65% gestation in both species. Prenatal development continues rapidly in the monkey, so that by birth a single layer of inner retinal neurons are present in the fovea, cones are three cells deep, inner segments are elongated, and outer segments are up to 50% of inner segment length. In contrast, human fovea does not reach a similar stage until several months after birth. The fovea is adult-like in monkey at 12 weeks and in human at 11-15 months, although human will mature further up to four to five years. This study shows that human fovea is less mature at birth than monkey but develops rapidly in infancy, suggesting that it may be even more susceptible to postnatal environmental influences than the commonly-used monkey model. PMID- 1624036 TI - Electrophysiological assessment of visual pathway function in infants. AB - The flash ERG and VEP have conspicuous immature features during the first 4 months following birth. The most marked maturational changes occur in ERG amplitude and VEP latency. Concurrent recording of the skin ERG and VEP provides information which is very useful in helping to arrive at a diagnosis in the young infant with nystagmus who appears to be blind and has a fundus of normal appearance. ERG and VEP features associated with Leber's Amaurosis, congenital cone dysfunction, albinism, optic nerve hypoplasia and unilateral hemisphere dysfunction are described. PMID- 1624037 TI - Neonatal eye growth and emmetropisation--a literature review. AB - The refractive development of the neonatal eye has been the subject of much study and debate. In this paper the hypothetical mechanisms of emmetropisation and their relationship to the development of refractive errors will be reviewed. The evidence supporting visual feedback control of eye growth will be described, and the role of ocular accommodation will be discussed. PMID- 1624038 TI - The premature retina: a model for the in vivo study of molecular genetics? AB - Retinopathy of prematurity is a disease of developing blood vessels. Although it is seen predominantly in premature infants requiring life support systems to survive, it does occur in full-term infants, infants with hypoxia, cyanotic heart disease and in stillborn infants. Although oxygen has been considered to be the prime aetiologic agent, evidence for this, particularly in recent years, is not compelling. The timing of the occurrence of the disease is closely related to the conceptional age of the infant rather than weeks post birth, birth weight, gestational age at birth. In addition, the case to case similarity of the disease, as well as the diverse cell types produced in unfavourable outcomes (cicatricial ROP), point to the possibility of an in utero insult to the clone of cells giving rise to the vascular endothelium providing blood supply to the neural retina. PMID- 1624039 TI - Light and the immature visual system. AB - Preterm neonates are cared for in an environment which is continuously and brightly lit, and is very different to that experienced at any other time of life. The amount of light reaching the neonatal eye is governed by two groups of factors. Physical factors include intensity, spectral characteristics and duration of light exposure. Physiological factors are: Frequency of eyelid opening, transmission of light through the closed eyelid, pupil reactivity and area, transmission by the ocular tissues and retinal surface area. Retinal irradiance declines with increasing postmenstrual age. Mechanisms by which light may affect the neonatal eye and clinical conditions in which light have been implicated are considered. PMID- 1624040 TI - Epidemiology of childhood blindness. PMID- 1624041 TI - Ocular teratology. Observations, speculations, questions, principles reaffirmed. AB - Teratology is most simply defined as "the study of environmental agents which disturb development". A more comprehensive definition is "the study of causes, mechanisms, and manifestations of developmental deviation, structural or functional." Teratology has several important purposes. Obviously, the most important is to protect future generations by identifying environmental agents that cause malformations. In this sphere, ophthalmologists are generally not the primary detectors. One notable exception is when Gregg, in 1941, recognised that an increase in congenital cataracts was due to a viral agent and brought rubella embryopathy to the attention of the medical community. Another pertinent reason for teratology is that it gives us insights into normal development. As Harvey said with such flair, "nature is nowhere accustomed more openly to display her secret mysteries than in cases where she shows tracings of her workings apart from the beaten path". PMID- 1624042 TI - Congenital extraocular muscular defects. PMID- 1624043 TI - Neonatal cataract: aetiology, pathogenesis and management. AB - We review the epidemiology, aetiology, pathogenetic mechanisms and clinical management of neonatal cataract. Visual development and the effects of visual deprivation in the infant with congenital cataract are discussed and related to the timing of surgery. Surgical techniques and the important operative and post operative complications are discussed. We review post-operative management and compare the different techniques available for aphakic correction, and describe the VEP changes found in patients with monocular cataract. PMID- 1624044 TI - Relapse following goniotomy for congenital glaucoma due to trabecular dysgenesis. AB - Three hundred and thirty-five eyes of 210 patients with congenital glaucoma due to trabecular dysgenesis were treated by goniotomy as the primary procedure in infancy. In 313 eyes (93.5%) glaucoma was controlled at one year following surgery. Using Kaplan Meier actuarial survival analysis we found that eyes controlled in infancy by one or more goniotomies are at risk of relapse of glaucoma for at least 15 years although 93% of eyes are still controlled five years after the initial surgery. Patients whose symptoms of congenital glaucoma presented at birth were more likely to relapse than those whose symptoms developed in the first few months of life. Eyes requiring multiple goniotomies in infancy were more likely to relapse than those controlled by a single procedure. PMID- 1624045 TI - Do we really understand the difference between optic nerve hypoplasia and atrophy? PMID- 1624046 TI - Intrauterine infection and the eye. PMID- 1624047 TI - Congenital lacrimal fistula. AB - Congenital lacrimal fistula is a rare developmental condition. Patients may be asymptomatic or have tearing from the fistula, the eye or both. The clinical features of 60 patients are reviewed, including presenting symptoms, presence of other lacrimal or systemic anomalies and morphology of the fistula. A detailed description is given of the surgical technique utilised in patients whose symptoms warrant surgical intervention. The results of this technique are presented and alternative treatment strategies are discussed. Theories of the aetiology of the condition are reviewed and morphological and histological evidence is presented to support our belief that congenital lacrimal fistulae represent aberrant canaliculi. PMID- 1624048 TI - Cryosurgery for acute retinopathy of prematurity: factors associated with treatment success and failure. AB - Cryosurgery for stage 3 plus acute retinopathy of prematurity (ROP) increases the probability of disease regression, but up to 25% of eyes may progress to retinal detachment and blindness in spite of treatment. In a series of 37 eyes in 23 patients treated at the Hammersmith Hospital an overall 75% of eyes reached a favourable outcome. We present these results in detail and analyse the apparent causes of treatment failure. Poor anatomical results (total retinal detachment and traction detachment involving the macula) were associated with inappropriate cryoprobe design and with zone 1 and rush-type disease. Poor functional results in the presence of a largely flat retina (marked macular ectopia and high myopia) appeared to be associated with delayed treatment during the period of evolution of the stage 3 lesion, and with the appearance of a more highly differentiated vascular shunt with early localised forward vitreous invasion. Suggestions for the refinement of existing gradings of acute ROP are made. PMID- 1624049 TI - Vitamin E therapy in retinopathy of prematurity. AB - Vitamin E is a fat soluble antioxidant and as a result it is able to scavenge free radicals derived from oxygen. The premature infant and the retina are likely to be particularly vulnerable to the deleterious effects of these oxygen derived free radicals, and as a result prophylactic vitamin E has been suggested for the management of retinopathy of prematurity (ROP). However, despite numerous trials, prophylactic supplementation with vitamin E remains controversial. This paper will critically review the use of vitamin E in ROP and consider the risk/benefit relationship of such treatment in premature infants. PMID- 1624050 TI - How do retinoblastoma tumours form? AB - The causes of retinoblastoma (RB) can now be described with considerable accuracy, although many details are still unclear. Understanding the genetic changes leading to RB has provided an awareness of general mechanisms of cancer development and progression, previously only suspected. From the basic understanding have come new diagnostic technologies that are now ready to be applied directly to RB patients and their families, and a rational approach, based on this understanding, will help us to develop new therapies that avoid the severe complications of conventional treatment. PMID- 1624051 TI - Federal support for dental education? PMID- 1624052 TI - Local analgesia infiltration. PMID- 1624053 TI - Health and safety in the laboratory. PMID- 1624054 TI - Laboratory technique for the construction of large scale teaching models. PMID- 1624055 TI - Ultrasonic vocalizations by rat pups: the primary importance of ambient temperature and the thermal significance of contact comfort. AB - We investigated the effects of isolation, huddling, and air temperature on ultrasound production by rat pups. Experiment 1 showed that ultrasound production by 8- to 9-day-olds was minimal at thermoneutrality and increased in response to small deviations of air temperature on either side of the thermoneutral zone. Experiments 2 and 3 showed that suppression of ultrasound production by contact with littermates is consistent with the thermal consequences of huddling. Experiment 4 showed that, contrary to previous conclusions, ultrasound production is not independent of ambient temperature in pups older than 10 days of age. Taken as a whole, these experiments emphasize (1) the importance of ambient temperature for the elicitation of ultrasound by rat pups of all ages studied, (2) the importance of thermal factors in the suppression of ultrasound by littermate contact, and (3) the manner in which different methods can change interpretations of the behavior and physiology of infant rats. PMID- 1624056 TI - The effects of early social isolation on the motivation for social play in juvenile rats. AB - Fifteen-day-old rats were subjected to one of three housing conditions: mother and-peer (family), peer, and isolation conditions. At 24 days of age, all subjects were rehoused individually. In Experiment 1, play behaviors were monitored in like-raised pairs. Despite their gross lack of social experience, isolation-reared subjects did not exhibit a deficit in frequencies of rough-and tumble play. It is concluded that the fundamental motivation for rough-and-tumble play is relatively independent of prior learning in rats. Indeed, their elevated dorsal contacts suggested that isolation-raised subjects may have higher appetitive motivation for play. In Experiment 2, the levels of social motivation were compared between family- and isolation-raised animals, using a T-maze. The isolation-raised animals made reliably more choices for social interaction reward over food reward than family-raised animals. Although inconclusive, the results from the two experiments suggest that prolonged social isolation increases the appetitive motivation for social play. PMID- 1624057 TI - Blood pressure increases in response to feeding in the term neonate. AB - We studied blood pressure and heart rate of 18 medically well newborn babies before, during, and after feeding. Seven were breast-fed and 11 bottle-fed and all were studied between 24 and 92 hr of age. There was an increase in heart rate associated with sucking on a pacifier but no additional increase with feeding. By 30-60 min after feeding, heart rate had returned to baseline value. Blood pressure, however, did increase in response to feeding and showed a greater increase in the breast-fed group than in the bottle-fed group. Systolic blood pressure rose from 72 mmHg in the basal state to 85 mmHg during the first 3 min of feeding in the bottle-fed babies and from 73 to 99 mmHg during comparable periods in the breast-fed babies. The results for diastolic blood pressure were similar except that changes within the bottle-fed group were not statistically significant. Bottle-fed babies rose only from 42 to 47 mmHg while breast-fed babies rose from 42 to 61 mmHg from basal conditions to feeding. Blood pressure responses to feeding may have implications for susceptibility to necrotizing enterocolitis, for future blood pressure liability in adulthood and for later hypertensive disease. PMID- 1624058 TI - Faces as reinforcers: effects of pairing condition and facial expression. AB - The reinforcing properties of faces were investigated in two experiments in which tones were first paired with an adult female face and subsequently tested for their ability to potentiate visual fixation when compounded with a checkerboard pattern. In Experiment 1, infants who had been presented six pairings of a 65-dB, 1000-Hz tone with a smiling face later fixated a checkerboard pattern significantly more when it was compounded with the tone than when it was tested alone. Infants in random and backward controls fixated the checkerboard pattern roughly equal amounts in the presence absence of the tone, and infants in a no tone control did not exhibit a novelty response when shifted from the face to the checkerboard pattern. In Experiment 2, facial expression was varied across groups and the effects on conditioning of a 65-dB tone that immediately preceded the face were studied. On test trials, greater fixation in the presence of the tone than in its absence was observed when a smiling or a surprised expression was presented, but not when a neutral expression was presented. Differences scores (fixation on tone minus no tone test trials) were significantly greater than zero in the smiling and surprised conditions, and significantly greater in the surprised condition than in the neural condition. These findings demonstrate the feasibility of a conditioned visual fixation paradigm for the study of the reinforcing properties of faces and of infant associative learning in general, and suggest that the expression portrayed by a face contributes to its effectiveness as a reinforcer. PMID- 1624059 TI - Analysis of the expression of a glucose-regulated protein (GRP78) promoter/CAT fusion gene during early Xenopus laevis development. AB - Developmental regulation of the expression of a glucose-regulated gene encoding a 78 kd protein, GRP78, has been characterized by microinjection of a rat GRP78/CAT chimeric gene into early Xenopus embryos. Tunicamycin-induced expression of the chimeric gene during Xenopus development was similar to the pattern of endogenous GRP78 protein synthesis, with expression first being detected at gastrula and increasing at least until the tailbud stage. Deletion analysis of the rat GRP78 promoter revealed that sequences between -154 and -130 were necessary for full tunicamycin-inducible and constitutive expression of the fusion gene. These results suggest that there is conservation of regulatory elements of the GRP78 promoter between rat and Xenopus. PMID- 1624060 TI - In vitro regulation of the innervation pattern of quail muscle fibers by quail and mouse neurons. AB - Myoblasts from rudiments of slow and fast muscle, anterior latissimus dorsi (ALD) and posterior latissimus dorsi (PLD) respectively, of 9-day-old quail embryos were cultured in vitro for a period of up to 60 days in order to give rise to well-differentiated muscle fibres. These fibres were innervated by neurons from either quail or mouse embryo spinal cord and their innervation pattern was examined by the visualization of acetylcholine receptors (ACh-R) and of acetylcholinesterase (ACh-E) activity at the neuromuscular contacts. In the culture system used, quail neurons always innervated muscle fibres at several sites and only when a fast-type activity was imposed on these neurons did a reduction in the number of the previously established neuromuscular contacts take place. In contrast, in the muscle fibres innervated by mouse neurons, a spontaneous reduction in the number of the previously established neuromuscular contacts occurred but this spontaneous reduction depended upon the level of differentiation reached by the muscle fibres in vitro. In the cultures of muscle fibres previously innervated by mouse neurons, the addition of quail neurons did not provoke any modification in the initial innervation pattern, and no quail ACh R cluster was observed. In contrast, in the muscle fibres previously innervated by quail neurons, the mouse neurons contacted these fibres, resulting in a decrease in the number of quail ACh-R clusters. These results emphasize the part played by neurons in the establishment of the innervation pattern when muscle fibres have reached a high level of differentiation. In vitro, the slow and fast characteristics of the muscle fibres do not influence this pattern. PMID- 1624061 TI - Immunohistochemical localisation of monoclonal antibody R 24-recognized ganglioside Glac2 in early chick embryos. AB - The spatio-temporal cellular expression and biosynthesis of ganglioside Glac2 was investigated in early chick embryogenesis. For demonstration of embryonic Glac2 biosynthesis, chick embryos of stage 0 and of stages 4-5 were incubated in vitro in the presence of radioactive sugar precursors. It was found that chick embryos synthesize Glac2 as early as at the blastula stage as well as at the gastrula stage, both within the area pellucida and the area opaca. In contrast to the biosynthetical findings immunohistochemical staining of the chick embryos at various stages by aid of the mouse monoclonal antibody (mAb) R 24, specific for the immunoepitope NeuAc alpha, 8NeuAc alpha, 3Gal beta less than, as present on the ganglioside Glac2, revealed a spatio-temporal cellular pattern of expression of this ganglioside in early chick embryos. Immunohistochemical staining of the chick embryo at stage 0 shows that all cells of the embryo, the extraembryonic epiblast and the yolk endoderm included, are mAb R 24-positive. At the intermediate streak stage (stage 3), the cranial part of the deep layer, the so called endophyll, is strongly mAb R 24-positive, whereas at the end of gastrulation (stage 5), mAb R 24-recognized epitopes appear to be restricted to a narrow band of deep-layer cells in the endophyllic crescent and to the yolk endoderm of the area opaca. At this stage, no labelling by the antibody is observed in cell layers of the future embryo. The beginning of neurulation (stage 7) is characterized by the expression of the mAb R 24-recognized epitope in the notochord, whilst the deep layer in the cranial part of the neural fold still expresses this epitope. No ecto- or mesodermal structures are stained by the antibody at this developmental stage. During further development (stage 12 and 13), mAb R 24-reactivity is restricted to the cranial part of the embryo with a preferential staining of cells of endodermal origin. At these stages, the notochord expresses mAb R 24 binding sites only in its cranial region. The spatial and temporal correlation between the presence of mAb R 24-recognized epitopes and the morphogenetic positioning of tissues may be indicative for a possible role of the ganglioside Glac2 in corresponding cellular interactions. PMID- 1624062 TI - [The role of the author in biomedical journals--I]. PMID- 1624063 TI - [The enigma of mild hypertension]. PMID- 1624064 TI - [Tossing pebbles into a pond, or ethics seen by a heretic]. PMID- 1624065 TI - [Further comments on the classification of stenocardia syndromes]. PMID- 1624066 TI - [Left ventricular false tendon: the most frequent cause of "innocent" murmur in childhood?]. AB - BACKGROUND: The left ventricular false tendon (FT) is an anomalous fibrous or fibromuscular band stretching across the left ventricle. The false tendons extend from the septum to the left ventricular free wall or, more rarely, from the septum to a papillary muscle. The association between FT and innocent cardiac murmur has been pointed out. The aim of the present study was to assess the incidence of FTs in children with a murmur classified as innocent. METHODS: Two groups of subjects were selected. Group A consisted of 253 children with: 1) systolic ejection murmur; 2) normal electrocardiogram and 3) absence of clinical data suggesting cardiac disease. Group B consisted of 240 children clinically free of cardiac disease, and without any cardiac murmur. A FT was diagnosed by means of 2D echocardiogram whenever a linear band stretching across the left ventricular chamber was evident in at least two sections. RESULTS: One hundred and sixty-one children of group A (63.6%) reflected a left ventricular FT; only in 3 patients out of 161 the FT was associated with a small ventricular septal defect, whereas in 158 children the FT was the only abnormal finding. A normal echocardiogram was observed in 71 children (28.1%) of group A; whereas in 21 patients (8.3%) a congenital heart disease was diagnosed. In group B, only 33 subjects (13.8%) had a FT. The different incidence of FT in the two groups (63.6% versus 13.8%) was statistically significant (p less than 0.01). CONCLUSIONS: The study shows that about two thirds of children with innocent heart murmur reflect a left ventricular FT. Furthermore, FT is far more common in subjects with innocent cardiac murmur than in normal subjects. The relationship between FT and murmur thus appears very likely, although not definitely proven. PMID- 1624067 TI - [Verapamil-induced gingivitis hypertrophica: a clinical case]. PMID- 1624068 TI - [Asymptomatic aortic dissection associated with a mitral prosthetic leak: a clinical case report]. AB - A case of aortic dissection ("DeBakey type III") in an asymptomatic 78-year-old woman is described. The patient underwent a mitral valve replacement (bioprosthesis Sorin) in June 1990 for severe mitral stenosis; in October 1990 she was admitted to our hospital for severe dyspnea and cardiac failure with good response to medical treatment. The routine echo color Doppler examination showed only a hint of paraprosthetic leak, which required further investigation by transesophageal echocardiography. This approach revealed the presence of a regurgitant jet extending from the prosthetic mitral valve toward the atrial septum. The examination of the thoracic aorta revealed the presence of a dissection flap; the color Doppler technique showed a bidirectional flow through the site of communication between the two lumina. The extension of the dissection from the aortic arch to the origin of the renal branches was confirmed by computerized axial tomography. We emphasize the importance of the transesophageal approach in elderly patients with aortic dissection, often asymptomatic. PMID- 1624069 TI - [The pathogenesis of dilated cardiomyopathy: current progress]. AB - The pathogenesis of dilated cardiomyopathy (DCM) is still unknown; however, some factors that seem to play an important role in the development of the disease have recently been identified: they are enteroviral infections, immune mechanisms and genetic factors. Enteroviral infection (particularly due to Coxsackie virus B) has long been suspected to be the cause of myocarditis and subsequent DCM. However, only recent techniques of genetic engineering have been able to demonstrate the presence of enteroviral RNA in endomyocardial biopsy of patients with DCM. The role of the viral particles contained in the myocardium is still undetermined. Changes in the immune system concerning cell-mediated and humoral immunity have been recently detected. It has been suggested that an autoimmune process could be the actual cause of DCM in some patients, rather than the consequence. The immune system is strictly related to the major histocompatibility complex. As in some autoimmune diseases, a relationship between DCM and HLA class II phenotype has been found: particularly the DR4 antigen seems to be associated with a high risk of disease. Besides immunogenetic factors, other genetic factors seem to play a role in the pathogenesis of DCM. In 6-8% of cases a familial history of cardiomyopathy has been observed. In clinical studies on familial DCM different phenotypes have been shown, suggesting that different genetic mechanisms are involved in the pathogenesis of the disease. At least two main mechanisms can be hypothesized: the transmission of "predisposing" factors or a defect in proteins essential for the cardiac muscle cell function. Viral agents, autoimmune reactions, immunogenetic and genetic factors seem to cause myocardial damage individually or with complex interactions: the research should be devoted to these topics in the future. PMID- 1624070 TI - [Idiopathic dilated cardiomyopathy: a persistent viral infection or an organ specific autoimmune disease? The trial of 2 major pathogenetic hypotheses]. AB - Aetiology and pathogenesis of idiopathic dilated cardiomyopathy (DCM) are uncertain. The two major pathogenetic hypotheses are: 1) autoimmunity; 2) persistent viral infection. Indirect evidence for virus association comes from the finding of raised titres of antibody to coxsackievirus in DCM, but infectious virus has never been isolated in myocardium from DCM patients. Bowles et al. using the slot-blotting technique reported that enteroviral RNA was commonly detectable in the myocardium of patients with myocarditis (53%) and with DCM (52%). Other groups using this as well as more refined hybridization techniques have failed to confirm such a high prevalence. Detection of enteroviral genomic RNA in cardiac tissue does not, however, imply active infection or pathogenicity. Thus the mechanisms of chronic myocardial damage in the absence of whole competent infectious virus remain uncertain. The other major pathogenetic hypothesis in DCM involves autoimmune mediated damage to myocytes. Circulating organ specific autoantibodies have been reported in a quarter of a group of patients with idiopathic DCM. This suggests that there may be autoimmune mechanisms operating at least in this subset of patients, but the exact relation of these antibodies to the pathogenesis and prognosis needs to be defined. The abnormal expression of major histocompatibility complex class II antigens on cardiac microvascular endothelium in endomyocardial biopsy tissue from DCM patients, and the reported association with HLA-DR4 phenotype lend further support to the autoimmune hypothesis. The viral and the autoimmune hypothesis in chronic myocarditis and in DCM are not mutually exclusive. In experimentally murine virus-induced myocarditis infectious virus can no longer be recovered from the myocardium after two weeks, although nucleic acid sequences of the viral genome are still detectable. The development of chronic inflammation takes place only in mice with a predisposing genetic background. Chronic myocyte damage is associated with the production of circulating heart-specific autoantibodies and autoreactive lymphocytes. In this animal model chronic myocarditis appears to be a virus-triggered or precipitated autoimmune disease, rather than a persistent viral infection with tissue damage due to active virus synthesis and replication. A similar transition from acute myocarditis into DCM may occur in man. PMID- 1624071 TI - [Surgical revascularization in acute myocardial infarct]. AB - To determine the potential role of emergency surgical revascularization as treatment of acute myocardial infarction (AMI), results in 79 patients undergoing operation for myocardial revascularization during AMI from January 1986 to January 1991 were reviewed. Clinical characteristics for inclusion in the study were: 1) emergency operation; 2) persistent angina not controlled by medical therapy; 3) fixed ST segment elevation until surgical procedure, independently from magnitude of enzymatic levels. The 79 patients were divided in 2 groups: 27 with AMI or evolving AMI (Group 1); 52 with AMI due to complications during PTCA (Group 2). Twenty-eight patients had extremely severe clinical conditions. Mean interval between the beginning of AMI and operation was 4.2 +/- 6.7 hours, with a statistically significant difference between Group 1 (8.7 +/- 10.0) and Group 2 (1.9 +/- 1.0). One hundred ninety-two grafts were performed (2.4 +/- 1.1 grafts/patient). Overall hospital mortality was 10.1% (CL 6.7-13.3) (8 deaths) with a difference between Group 1 [18.5% (CL 10.7-25.3)] and Group 2 [5.8% (CL 4.7-6.6)] (p = 0.074). The incidence of perioperative myocardial infarction was 30.4% (CL 24.9-35.1) for that one in the area of ischemic muscle and 2.6% (CL 0.8 4.1) for infarction in remote muscle. Multivariate analysis for the entire series (79 patients) identified as independent predictors of increased in-hospital mortality: preoperative cardiogenic shock (p = 1.000E-4) and hyperlipidemia (p = 0.008). In Group 1 multivariate analysis identified as independent predictors of increased in-hospital mortality: the attempt of revascularization by PTCA and hyperlipidemia; in Group 2: preoperative need of mechanical ventilatory support.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1624072 TI - [HLA polymorphism in the susceptibility or resistance to dilated cardiomyopathy]. AB - Much of the surrounding studies on the association between HLA and diseases reflects a new insight into the key role of HLA molecules in the generation and regulation of the immune response. HLA molecules, on the surface of antigen presenting cells, bind foreign peptides. This HLA-antigen complex is then recognized by T lymphocytes and triggers the alloresponse against the peptide. Since many diseases associated with peculiar HLA antigens are thought to be autoimmune, the idea that certain Major Histocompatibility Complex (MHC) molecules could form complexes with self-peptides in anomalous ways, leading to an autoimmune reaction, is particularly attractive. Recent advances in molecular technology, x-ray crystallography and DNA studies have allowed the determination of the three-dimensional structure of some HLA class I and II molecules and also the amino acid sequences involved in binding of antigen fragments. This new information has prompted a search for differences, at the amino acid level, between HLA alleles previously shown to be positively or negatively associated with a pathology. Our own experience on the immunogenetic aspect of dilated cardiomyopathy (DCM) allowed us to assess some predisposing (HLA-DR4, DR5, C4A4) and protective (HLA-DR3) factors for DCM. Clinical heterogeneity also seems to imply a peculiar genetic background. The actual research is addressed to the study of the antigen binding site sequences and to the consideration of other new loci such as those entrapped within the HLA class III subregion (HSP70) and those lying within the class II region (PSF). PMID- 1624073 TI - Gm and Km allotypes in autoimmune diseases. AB - The associations or linkages between the polymorphisms of the Gm and Km immunoglobulin allotypes and the susceptibility to autoimmune diseases, including diseases with immuno-pathological pathogenesis are reported in this review. These diseases include multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, insulin-dependent diabetes mellitus, Crohn's disease, coeliac disease, Graves' disease, atrophic thyroiditis, Hashimoto's thyroiditis, myasthenia gravis, chronic active hepatitis, alopecia areata, uveitis, vitiligo, Turner's syndrome, glomerular nephritis, Berger's disease and idiopathic dilated cardiomyopathy. Immunoglobulin allotypes are described as well as the statistical methods used to analyse the data. PMID- 1624074 TI - [The monitoring of plasma digoxin levels during acute digitalis poisoning treated with Fab anti-digoxin fragments]. AB - Life-threatening digitalis intoxication is treated using digoxin specific antibody fragments (Fab) that bind and inactivate the drug. The free digoxin serum concentration could be useful in the management of Fab-treated patients, but the standard methods of measurement can be clinically misleading because Fab anti-digoxin interferes with digitalis immunoassay measurements. A case involving Fab therapy of a digoxin overdosed patient, in which two laboratory methods gave very different results, is reported. The radioimmunologic assay (RIA), widely used in laboratories, yielded high values without relation to true serum free digoxin concentration. On the contrary, the recently introduced fluoroenzymatic sequential immunoassay (FEIA), which accurately measures free glycoside concentration, was a valuable aid in monitoring Fab treatment. Therefore, cardiologists' knowledge of a possible interference of specific anti-digoxin fragment treatment with many immunoassays may greatly enhance the rational management of these patients. PMID- 1624075 TI - Experimental study on the effects of sclerosants for esophageal varices on blood coagulation, fibrinolysis and systemic hemodynamics. AB - The effects of five sclerosants used for treating esophageal varices on blood coagulation and fibrinolysis, systemic hemodynamics, and vascular endothelial cells were studied in mongrel dogs. With each sclerosant, hemolysis and a decrease in the platelet count were observed. Changes in the blood coagulation system occurred immediately after sclerosant administration. Prolongation of the PT and APTT and decreases in fibrinogen and alpha 2-PI were seen in the thrombin (TH), sodium tetradecyl sulfate (STS), and ethanolamine oleate (EO) groups. Polidocanol (PO) and absolute ethanol (ET) had less pronounced effects on these systems. A transient decrease in the cardiac index (CI), pulmonary artery pressure (PAP) and pulmonary artery resistance (PAR) was observed with the administration of the sclerosants, especially in the TH and STS groups. Excessive vascular endothelial damage was observed in the ET group, marked damage was seen in the EO and STS groups and slight damage was recorded in the PO and TH groups. PMID- 1624076 TI - Human pancreatic polypeptide, neuropeptide Y and peptide YY reduce the contractile motility by depressing the release of acetylcholine from the myenteric plexus of the guinea pig ileum. AB - Transmural stimulation (TS; 15 V, 0.5 msec, 1-5 Hz, for 30 sec) caused a contraction in a frequency-dependent manner of the longitudinal muscle with myenteric plexus of the guinea pig ileum. Two-min premedication with human pancreatic polypeptide (HPP, 10(-8) M-10(-6) M), neuropeptide Y (NPY, 10(-8) M 10(-6) M), and peptide YY (PYY, 10(-8) M-10(-6) M) partially, by less than 35%, reduced TS (15 V, 0.5 msec, 10 Hz)-evoked contraction in a dose-dependent manner without affecting the resting tensions. Hexamethonium, phentolamine, prazocine, yohimbine, propranolol, naloxone and theophylline had no effects on the inhibitory actions of these peptides on TS-evoked contractions. TS (15 V, 0.5 msec, 10 Hz)-evoked 3H-ACh release was significantly reduced by 2-min premedication of HPP (10(-6) M), NPY (10(-6) M) and PYY (10(-6) M). The order of potency of these depressant effects on TS-evoked contraction and 3H-ACh release was PYY greater than NPY greater than HPP. It is suggested that the members of PP family have inhibitory effects on the contractile motility by depressing ACh release from myenteric plexus of the guinea pig ileum. PMID- 1624077 TI - Prostaglandin E1 enhances hepatic portal venous flow by dilating the portal vascular bed in 70% hepatectomized dog. AB - The effects of portal, hepatic arterial and femoral venous administration of prostaglandin E1 (PGE) on portal venous flow (PVF) and hepatic arterial flow HAF were examined before and after 70% hepatectomy in anesthetized dogs. In the hepatectomized condition, portal venous administration of PGE (0.5 microgram/kg/min) caused an increase in PVF without any change in systemic arterial pressure (SAP). HAF was unchanged following the injection. The portal effect of PGE on PVF was dose-dependent, and a reduction in portal venous resistance was seen. However, the same dose of PGE failed to change PVF under intact liver conditions. Hepatic arterial administration of PGE (0.5 microgram/kg/min) brought no significant change in PVF or HAF, with or without hepatectomy. Femoral venous administration of PGE (0.5 micrograms/kg/min) produced an increase in PVF concomitant with a significant decrease in SAP. HAF showed no change after the injection. A decrease in PVR was seen only in the hepatectomized condition. It is concluded that PGE is potent in increasing PVF in the hepatectomized condition, and the portal vasculature is involved as the site of action. PMID- 1624078 TI - Endotoxin levels in cirrhotic rats with sterile and infected ascites. AB - Endotoxin levels were measured in sterile and bacterially infected ascites in a rat model of phenobarbital and carbon tetrachloride induced cirrhosis was used. An improved chromogenic substrate assay was used to measure endotoxin. All rat ascites specimens were positive for endotoxin. In culture-negative ascites (n = 8), it ranged from 0.05 EU/ml to 0.14 EU/ml (0.08 +/- 0.04 EU/ml, mean +/- SD) (Escherichia coli 0111:B4 endotoxin was used as a reference). In culture-positive ascites (premortem n = 3, postmortem n = 1), it ranged from 0.78 EU/ml to 1.8 EU/ml (1.29 +/- 0.59 EU/ml, mean +/- SD). All rats with premortem culture positive ascites died within two days. This model is useful to study ascites endotoxin levels. In this study, increasing levels of ascites endotoxin correlated with spontaneous bacterial peritonitis and death. PMID- 1624079 TI - Abnormal GH secretion in liver cirrhosis: evaluation of using GRF test and TRH test. AB - To evaluate abnormal secretion of growth hormone (GH) in cases of liver diseases, the authors performed a loading test of growth hormone-releasing factor (GRF) and approximately one week later, a loading test of thyrotropin-releasing hormone (TRH), and measured serum GH in 15 cases of liver cirrhosis (LC), 5 with chronic active hepatitis (CAH), and 5 controls. In the TRH test, 8 of 15 LC patients showed a peak GH value of 6 ng/ml or more and were classified as the TRH responder group (LC-R). Seven other LC patients showing a peak GH value of less than 6 ng/ml were classified as the TRH-non-responder group (LC-NR). None of the CAH cases or controls showed a peak GH value of 6 ng/ml or more. In GRF test, the response of GH was poor in all 8 in the LC-R group. The responses in the LC-NR group were significantly greater than those in the LC-R group from 15 to 90 minutes after the GRF loading. In the LC-R group, greater impairment of liver function was indicated by total bilirubin, serum protein and cholinesterase values compared to the LC-NR group. Fischer's ratio was significantly lower in the LC-R group. In cases of liver diseases, Fischer's ratios negatively correlated with the peak GH values in the TRH test (r = -0.679, P less than 0.01). These results suggest that in LC cases showing a paradoxical GH response to TRH, the GH response to GRF which is a GH stimulatory hormone, is decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1624080 TI - The relationship between biliary secretion of bilirubin and glutathione in the rat. AB - The relationship between biliary secretion of bilirubin and glutathione was investigated by infusing bilirubin solution (200 nmol/min/100 g body wt) into Sprague-Dawley rats and measuring bilirubin and glutathione in the bile. Hepatic glutathione level, when modified between the range of 1-10 mumols/g liver wt, did not affect biliary maximal secretory rate (Tm) of bilirubin (80 nmol/min/100 g body wt). However, when biliary secretion of bilirubin exceeded 10 mM or 30 nmol/min/100 g body wt, biliary secretion of glutathione was markedly impaired while the bile flow remained relatively constant. Thus, bilirubin impaired the biliary secretion of glutathione selectively compared to its effect on bile formation. The results indicate that the mechanisms of biliary secretion of the two physiological substances, bilirubin and glutathione, are closely related. PMID- 1624081 TI - Effects of secretin on bile production in two kinds of cholestatic models by choledocho-caval fistula and bile duct ligation in rats. AB - Secretin is known to stimulate bile flow from the bile duct epithelium. To investigate the effects of secretin in cholestasis, we studied the response of the bile flow and the excretion of biliary components to secretin using two cholestatic models with or without damage to the bile duct epithelium. The model without bile duct epithelial damage was a choledocho-caval (CC) fistula over a 24 hour period, and the model with bile duct damage was a bile duct ligation over a 48-hour period. Secretin was administered by intravenous infusion for 30 minutes and bile was collected for 120 minutes. Controls were given saline similarly. The bile flow and biliary bicarbonate excretion rate were significantly increased after secretin infusion in the CC fistula rats when compared with the control rats, but no stimulation by secretin was observed in the ligated rats. These data indicate that secretin-induced bile production was enhanced under cholestatic conditions with no bile duct epithelial disturbance. PMID- 1624082 TI - A case of jejunal gastrinoma diagnosed by percutaneous transhepatic portal venous sampling. AB - A 63-year-old male was admitted to our department for further examination of hypergastrinemia. Secretin provocation test and calcium infusion test suggested Zollinger-Ellison syndrome and percutaneous transhepatic portal venous sampling (PTPVS) demonstrated gastrinoma in the jejunum, although CT, ultrasonography and angiography could not accurately detect the location of the gastrinoma. Laparotomy findings showed a solid tumor 1.5 cm in diameter in the jejunal mesentery 5 cm distal to the ligament of Treitz, and primary gastrinoma was confirmed in the submucosa of the jejunum immediately adjacent to this tumor. An immunohistochemical study using the PAP method revealed gastrin secreting cells in the tumor. In addition to this case of jejunal gastrinoma, a review of literature in Japan and other countries was presented. PMID- 1624083 TI - Adult descending colocolic intussusception caused by a large lipoma. AB - Adult intussusception is uncommon and varies considerably from the more common occurrence of this disorder in infants and children. Although lipoma represents the most common benign tumor of the colon, it is a relatively rare cause of gastrointestinal symptoms. A rare case of adult intussusception of the descending colon caused by a giant lipoma is presented and discussed. PMID- 1624084 TI - Sarcoidosis with tumorous hepatic and bone lesions mimicking disseminated malignancy: a case report. AB - An asymptomatic 49-year-old woman with a diffuse abnormal shadow detected on a routine chest rentogenogram was referred for evaluation. Ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) revealed space occupying lesions in the liver and spleen. Lymphadenopathy was observed in the mediastinum and abdomen on CT, and multiple lesions of low signal intensity were observed in the spine on MRI. Furthermore, the presence of multiple tumorous nodules in the liver suggesting metastatic hepatic cancer was demonstrated on laparoscopy. Biopsy of the liver tumors revealed sarcoidosis; transbronchial biopsy specimens showed identical histological features. After administration of prednisolone for one month, the space-occupying lesions in the liver, spleen and spine improved. This case of sarcoidosis exhibited hepatic tumorous nodules and space-occupying lesions in the spleen and the spine which mimicked the presence of metastatic hepatic cancer. PMID- 1624085 TI - Does H2 receptor antagonist-resistant ulcer exist?--A review based on bioavailability in man. AB - Recently the term H2 receptor antagonist-resistant (H2RA-resistant) ulcer has been used increasingly commonly, instead of the conventional term of intractable ulcer, to designate an ulcer which does not respond to treatment with an H2 receptor antagonist (H2RA). However, many authors report that an H2RA resistant ulcer can be cured by increasing the dosage of H2RA, or using another H2RA. In this study, the absorption and bioavailability of oral doses of each of three H2RAs, which are possible factors in these effects, were studied in healthy volunteers. The results showed that there was a great difference in bioavailability between cimetidine (80%), famotidine (39%) and ranitidine (50%). The lower bioavailability of famotidine and ranitidine may be partially explained by the following facts: 35.8% to 57.8% of orally administered famotidine is decomposed in gastric acid (pH 1) before absorption; and about 50% of ranitidine is metabolized in the liver before distribution (first-pass effect). Thus famotidine and ranitidine should be carefully administered to patients with slow gastric emptying and hepatic dysfunction, respectively. In general practice, many patients may not respond well to treatments because of their poor absorption, or extensive metabolism. In such cases, further effectiveness and safety could be expected if another H2RA, appropriately tailored to patients' conditions, were chosen. On the basis of these findings, it would seem premature to conclude that H2RA-resistant ulcer exists. PMID- 1624086 TI - Protective effect of deferoxamine for acetaminophen induced liver injury. PMID- 1624087 TI - Canalicular transport mechanisms of fluorescent bile acid in hepatocyte doublets. PMID- 1624088 TI - Somatolactin stimulates in vitro gonadal steroidogenesis in coho salmon, Oncorhynchus kisutch. AB - Somatolactin (SL), a newly discovered pituitary hormone of the teleost pars intermedia, is structurally similar to prolactin and growth hormone. The function(s) of SL are not yet established, although evidence suggests that it may play a role in reproduction. Possible steroidogenic activity of coho salmon SL was tested and compared with gonadotropin I (GTH I) in incubations of ovarian follicles or testicular fragments. SL stimulated production of 11 ketotestosterone and testosterone by testicular fragments, and production of estradiol by ovarian follicles in a concentration-dependent manner. However, the steroidogenic activity of SL was considerably less than that of GTH I. These results suggest that SL may play a role in regulation of gonadal function in salmon. PMID- 1624089 TI - Tissue-specific sensitivity of chromatin and the vitellogenin gene to micrococcal nuclease after continuous exposure of salmon (Salmo salar) to 17 beta-estradiol. AB - Smoltified Atlantic salmon (Salmo salar), 2 years old and weighing 217 +/- 13 g, were treated for 2 weeks with 17 beta-estradiol containing silastic capsules implanted intraperitoneally. Control fish received empty capsules. Vitellogenin, present in the blood of both groups of fish, was enhanced by estradiol treatment. Nuclei were isolated from liver, blood cells, and brain and incubated with increasing concentrations of micrococcal nuclease (EC 3.1.31.1). In liver there were more mononucleosomes as a percentage of total chromatin in hormone-treated than in control fish. Using vitellogenin cDNA as a probe the highest hybridization signals were seen when 2 to 4% of the chromatin was digested to mononucleosomes. In blood cell and brain nuclei independent of the extent of the chromatin released the hybridization signals remained low. The expression of the vitellogenin gene in immature females was potentiated by exogenous estradiol to give increased micrococcal nuclease sensitivity of the chromatin without enhancement of the hybridization level. Micrococcal nuclease digestion and hybridization of the vitellogenin gene demonstrated that the hepatic specificity of vitellogenin synthesis is manifested as structural modulations of the chromatin containing the vitellogenin gene. PMID- 1624090 TI - Effects of melatonin implants on insulin-like growth factor 1 in male red deer (Cervus elaphus). AB - Red deer stags have a seasonal pattern of growth, alternating between periods of summer weight gain and winter weight loss that are influenced by photoperiod and by exogenous melatonin. A seasonal pattern of plasma insulin-like growth factor 1, also influenced by photoperiod, underlies the seasonal growth pattern. The present studies aimed to determine the influence of exogenous melatonin, administered at various times of the year, on plasma IGF1 in adult red deer stags in New Zealand at 45 degrees S. In one study, 7-year-old stags (N = 9) were allocated to one of three treatment groups, either control or subcutaneous melatonin (3 x 18-mg coated implants (Regulin) per month) from November to February or from December to February. Blood was sampled, the stags were weighed, and antler status was recorded over 17 months. Melatonin treatment advanced the seasonal patterns of rise and fall of plasma IGF1 and of weight gain and loss. The cessation of melatonin treatment in February produced early antler casting and a second (out-of-season) antler and increased IGF1. In a second study, 4-year old stags (N = 30) were allocated to one of six treatment groups as follows: three melatonin implants per months for 6 consecutive months beginning on 22 June, i.e., winter solstice, 4 August, 16 September, and 23 October; three melatonin implants per month for 12 months beginning on 22 June; and an untreated group. All animals were sampled as before for 12 months. Melatonin treatment beginning in July and August did not prevent the seasonal peak in IGF1, but the amplitude was lowered and antler casting delayed. PMID- 1624091 TI - Some polypeptides in the nervous system of the marine worm, Nereis diversicolor, are related to the sodium influx stimulating peptide of the pulmonate freshwater snail, Lymnaea stagnalis. AB - Total mRNA, extracted from brain of the marine worm, Nereis diversicolor (Annelida, Polychaeta), was translated either in vitro using a rabbit reticulocyte lysate or in ovo (Xenopus laevis oocyte). The synthesized polypeptides were analyzed by electrophoresis and Western blotting techniques using polyclonal antisera raised against three peptides: sodium influx stimulating peptide (SISP) sequences 10-19 and 67-76 and a monoclonal antibody raised against purified native SISP (1-77) of Lymnaea stagnalis. Among the products translated in vitro, three polypeptides of 80, 72, and 64 kDa were recognized by the anti-SISP (10-19) polyclonal antiserum and by the monoclonal antiserum, but not by anti-SISP (67-76). Some of the in ovo translated products showed almost identical immunoreactivity to both the anti-SISP (10-19) and the monoclonal antibody. These polypeptides have molecular masses of 80, 72, and 43 kDa. No polypeptides were recognized by anti-SISP (67-76). Western blotting analysis of brain extracts revealed a number of proteins that reacted with the antiserum raised against SISP (10-19) and the monoclonal antiserum. Several perikarya of brain ganglionic nuclei and ventral nerve cord were immunoreactive to anti-SISP (10-19). The monoclonal antiserum gave similar results, although with a less intense immunoreaction. The infracerebral region was also stained, suggesting that the immunoreactive material is released as a true neurohormone into the hemolymph. The largest polypeptides, in particular those translated from brain mRNA, could be neuropeptide precursors containing a SISP-related sequence. PMID- 1624092 TI - Evaluation of a radioimmunoassay for the measurement of amphibian parathyroid hormone. AB - A commercial mid-region to carboxyl-region parathyroid hormone (PTH) radioimmunoassay (RIA) for measurement of PTH concentration in serum of humans was evaluated for its ability to detect amphibian PTH. The recovery of known amounts of human PTH added to aliquots of pooled frog serum demonstrated that frog serum does not interfere with the RIA system. The mean intraassay coefficient of variation was 0.11. During the spring and summer removal of the parathyroid glands from frogs resulted in significant decreases in serum calcium levels which the RIA revealed were associated with significant decreases in PTH levels. In the winter the parathyroid glands of frogs showed histological changes associated with inactivity. Also, parathyroidectomy of winter frogs did not affect serum calcium concentrations, and PTH levels of experimental and control animals were below or near the level of detection. PMID- 1624093 TI - Calcitonin gene-related peptide: an inhibitor of bullfrog (Rana catesbeiana) gallbladder contraction in vitro. AB - The presence of a calcitonin gene-related peptide (CGRP)-like material was demonstrated in the gallbladder of the bullfrog, Rana catesbeiana, using immunocytochemistry and confirmed by radioimmunoassay. An intense immunocytochemical reaction was observed in nerves located in the smooth muscle layers and associated with blood vessels. No immunoreactive nerve fibers were associated with ganglia, nor were immunoreactive cell bodies observed. Radioimmunoassay showed that 25.03 +/- 2.5 pmol/g tissue of CGRP-like material was present. In vitro tension studies using gallbladder strips showed that CGRP exerted an inhibitory effect on both acetylcholine- and cholecystokinin octapeptide-induced tension but had no effect on KCl-, norepinephrine-, or cerulein-induced tension. CGRP may act directly on the gallbladder smooth muscle to inhibit contraction. PMID- 1624094 TI - The pressor response to exogenous angiotensin I and its blockade by angiotensin II analogues in the American alligator. AB - We examined the pressor response to exogenous, nonnative angiotensin I (ANG I; bullfrog, turtle, and fowl) in the conscious American alligator, Alligator mississippiensis. In addition, the inhibitory effects of three ANG II analogues ([Sar1, Ala8], [Sar1, Thr8], and [Sar1, Ile8]ANG II) on the pressor responses to angiotensin I (fowl ANG I, [Asp1, Val5, Ser9]) were also examined. Intravenous administration of bullfrog, turtle, and fowl ANG I at 0.1, 0.5, and 1.0 micrograms/kg produced dose-dependent increases in arterial blood pressure. [Val5]ANG II at 0.05, 0.1, and 0.5 micrograms/kg, or NE at 2 micrograms/kg also produced dose-dependent increases in blood pressure. [Sar1, Ile8]ANG II and [Sar1, Ala8]ANG II (10 micrograms/kg/min) both attenuated the pressor response to fowl ANG I whereas [Sar1, Thr8]ANG II (10 micrograms/kg/min) produced no significant blockade. These data demonstrate: (1) All three exogenous ANG I molecules exert potent vasopressor responses in the alligator, (2) [Sar1, Ile8]ANG II is the most effective ANG antagonist, and (3) the alligator appears to possess a renin-angiotensin system similar to that found in other vertebrates. PMID- 1624095 TI - Prostaglandins and teleost neurohypophyseal hormones induce premature parturition in the guppy, Poecilia reticulata. AB - Administration of PGE2, PGF2 alpha, isotocin, and vasotocin to pregnant guppies during late gestation induced premature parturition. Indomethacin (10 micrograms/g body wt), the cyclooxygenase inhibitor, did not inhibit parturition at term, suggesting that some lipoxygenase metabolites may be involved in the induction of parturition. Pituitary extract, as well as LH-RH, did not induce premature parturition. It may be that in the guppy, in which ovulation occurs at the end of gestation just prior to parturition, gonadotropin is not involved in the induction of ovulation and parturition. PMID- 1624096 TI - In vitro bioactivities of various forms of GnRH in relation to their susceptibility to degradation at the pituitary level in the rainbow trout, Oncorhynchus mykiss. AB - In vitro potencies of native and modified forms of salmon and mammalian gonadotropin-releasing hormone (GnRH) were studied in relation with their susceptibility to degradation by intact pituitary cells maintained in culture. The kinetics of degradation and the origin of the proteases involved in this process were examined. All the molecules tested (native and modified forms) were equipotent at doses between 10(-6) and 10(-7) M in inducing GtH release by cultured pituitary cells. On the other hand, their effectiveness differed at 10( 9) and 10(-8) M leading to the establishment of the following hierarchy of bioactivity: the native forms, LHRH and sGnRH, were the less potent, the fish analogues (DAla6Pro9Net)sGnRH and (DArg6Pro9Net)sGnRH were the more potent, and mammalian analogues with substitutions at position 6 and/or 10 were intermediate in potency. The native form sGnRH was weakly degraded while no degradation of the modified molecules was observed. The degradation of the native sGnRH occurred after 12 and 24 hr of incubation and the results indicate that the peptidases involved are released from the cells into the incubation medium. PMID- 1624097 TI - Hormonal effects on glycogen metabolism in isolated hepatocytes of a freeze tolerant frog. AB - To determine whether specific hormonal responses were involved in the production of cryoprotectant (glucose) by liver of the freeze tolerant wood frog, Rana sylvatica, metabolically active hepatocytes were isolated in reasonable yields (mean 20.1 +/- 1.30% SEM, n = 29) by in situ liver perfusion with collagenase. Freshly isolated cells from autumn-collected frogs contained large amounts of glycogen (650 mumol glucosyl units/g packed cells) and produced glucose from this endogenous reserve at a rate of 10 mumol g-1 hr-1 at 0 degrees. Glucose output from cells was highly responsive to the addition of hormones; rates of glucose release increased 2.1-, 1.7-, and 1.7-fold with the addition of 10(-7) M bovine glucagon, 10(-7) M epinephrine, and 5 x 10(-6) M dibutyryl-cyclic AMP, respectively. Norepinephrine, 5-hydroxytryptamine, and bovine insulin were without effect at 0.1 microM/l. Hormone stimulation of glucose release was correlated with an increase in both the total activity and the percentage a of glycogen phosphorylase in hepatocytes. However, none of the hormones tested affected the kinetic properties of hepatocyte pyruvate kinase, suggesting the absence of covalent modification control of the enzyme. The data indicate that the freezing-stimulated production of large quantities of glucose as a cryoprotectant by R. sylvatica liver does not involve qualitative differences in the hormonal control of liver glycogenolysis, compared with other lower vertebrates. However, quantitative differences were seen, such as the much greater phosphorylase activity, 4.38 +/- 0.33 mumol min-1 g-1 packed cells, in freshly isolated R. sylvatica hepatocytes compared with 0.36 +/- 0.06 mumol min-1 g-1 in Rana pipiens hepatocytes. PMID- 1624098 TI - Corticotropin-releasing factor stimulates metamorphosis and increases thyroid hormone concentration in prometamorphic Rana perezi larvae. AB - Attempts to identify a hypothalamic molecule that stimulates thyrotropin (TSH) secretion from amphibian pituitary have been unsuccessful to date. The effects of mammalian (ovine and human) corticotropin-releasing factor (CRF) on the thyroid function of prometamorphic (Taylor & Kollros stages XI-XVII) (Taylor and Kollros, 1946) Rana perezi larvae were studied. Chronic treatments with both ovine and human CRF (oCRF, hCRF) stimulated metamorphosis while delaying larval growth. Chronic hCRF (1 microgram) administration induced 3.2- and 5.3-fold increases in whole body concentration of thyroxine (T4) and triiodothyronine (T3), respectively. In contrast, the 0.5-microgram dose of hCRF stimulated a significant (3.4-fold) increase in whole body concentration of T4 but not of T3. Histological studies of the thyroid gland revealed a 22% increase in the number of follicles per section as a result of the chronic treatment with oCRF (1 microgram). Acute oCRF (2 micrograms) treatment induced a significant increase in T4 concentration at 4 hr (1.3-fold) and 8 hr (2.3-fold) postinjection. T3 concentration was not altered. These results support previous reports and lead us to conclude that a CRF-like peptide, and not TRH, is involved in the regulation of thyroid activity in anuran amphibians during metamorphosis. PMID- 1624099 TI - Serum gonadotropins and gonadal steroids associated with ovulation and egg production in sea turtles. AB - Changes in serum concentrations of gonadotropins and gonadal steroids during the periovulatory period were monitored in green, Chelonia mydas, and loggerhead, Caretta caretta, sea turtles. Turtles were from natural populations that nest on a coral island on the Great Barrier Reef. After nesting, each turtle was transferred to a holding tank and held for a maximum of 8 days. A time series of blood samples was obtained from each of five sea turtles (three C. mydas and two C. caretta) starting immediately after nesting and then at approximately 12-hr intervals until the time of release. Prior to release back into the ocean, each turtle was examined by laparoscopy to verify that ovulation had occurred. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (PRO), and testosterone (T) in both species exhibited significant changes during this period. Surges of FSH, LH, and PRO were evident within approximately 20 to 50 hr after each turtle had nested. The significant change in FSH concentration during the periovulatory period is the first such report for a reptile. Coincident with maximal concentrations of FSH, LH, and PRO was a decline in T concentrations in both species. Estradiol-17 beta concentrations were near or below assay sensitivity in the C. mydas, whereas those in the C. caretta were detectable but exhibited no significant changes. The dynamic changes in FSH, LH, PRO, and T concentrations are consistent with the hypothesis that these hormones facilitate specific physiological events during ovulation and egg production. PMID- 1624100 TI - Biosynthesis and axonal transport of multiple molluscan insulin-related peptides by the neuroendocrine light green cells of Lymnaea stagnalis. AB - The neuroendocrine light green cells (LGCs) control body growth and metabolism of the freshwater snail, Lymnaea stagnalis. These cells, located in the cerebral ganglia, use the peripheries of the median lip nerves (MLNs) as the neurohemal area. The LGCs express four members of a gene family encoding the precursors of distinct though related molluscan insulin-related peptides (MIPs). The molecular characterization and biosynthesis of MIPs have been investigated. MLN extracts were first size fractionated using gel permeation chromatography, and a major peak that coeluted with bovine insulin was further resolved using reverse phase high performance liquid chromatography. Amino acid composition analysis revealed that the four MIPs were present, as encoded by the MIP genes. Biosynthesis and axonal transport of the MIPs were studied in vitro with LGC systems in a series of pulse-chase incubations in combination with gel permeation chromatography analysis. During the pulse period of 20 min MIP precursors were formed in the LGC cell bodies. During the subsequent chase period these precursors were converted to MIPs and C peptides, which were transported to the LGC axon terminals in the MLNs for storage and release. The MIP precursors seem to be processed similarly to the insulin precursor in pancreatic islets. PMID- 1624101 TI - Estrogen and a calcium flux dependent factor modulate the calbindin gene expression in the uterus of laying hens. AB - The dependency of calbindin 28K synthesis on estrogen and vitamin D and its relationship with calcium transfer were investigated in the uterus of laying hens by dot blot hybridization analysis using as a probe a cDNA coding for calbindin. Estrogen stimulated growth of the oviduct and uterine calbindin synthesis in juvenile D-deficient female chicks. In laying hens, calbindin mRNA increased most markedly during shell deposition but calbindin concentrations did not fluctuate during the ovulatory cycle. Suppression of shell formation within a few hours reduced calbindin mRNA levels and lowered uterine calbindin concentrations when egg expulsions were continued for several days. The concentration of calbindin and its mRNA increased when shell formation resumed in hens previously laying shell-less eggs. These increases were maintained in hens parathyroidectomized just before shell resumption. Lowering dietary calcium decreased uterine calcium transfer and calbindin concentration but its mRNA level was unaffected. It is suggested that uterine calbindin synthesis is regulated in a tissue-specific manner through transcriptional mechanisms irrespective of change in vitamin D; calbindin synthesis is stimulated by estrogens as part of its effect on oviductal growth but its regulation predominantly involves a calcium flux dependent factor associated with shell calcification. PMID- 1624102 TI - Competitive exclusion of diarrheagenic Escherichia coli (ETEC) from human enterocyte-like Caco-2 cells by heat-killed Lactobacillus. AB - Diarrheagenic Escherichia coli (ETEC) bearing CFA/I or CFA/II adhesive factors specifically adhere onto the brush border of the polarized epithelial human intestinal Caco-2 cells in culture. Heat-killed Lactobacillus acidophilus strain LB, that adheres onto Caco-2 cells, inhibits diarrheagenic Escherichia coli adhesion in a concentration-dependent manner. Since the L. acidophilus does not express ETEC-CFA adhesive factors, it can be postulated that the heat-killed L. acidophilus LB cells inhibit diarrheagenic E. coli attachment by steric hindrance of the human enterocytic ETEC receptors. PMID- 1624103 TI - Cloning of the phospho-beta-galactosidase gene in Escherichia coli from lactose negative mutants of Streptococcus mutans isolated following random mutagenesis with plasmid pVA891 clone banks. AB - In order to mutagenize Streptococcus mutans a marker rescue plasmid, pVA891, was employed. The plasmid was ligated with Sau3AI digested chromosomal DNA fragments from S. mutans GS-5IS3 and the resultant plasmids were amplified in Escherichia coli. These plasmids were then randomly integrated into the chromosome of strain GS-5IS3 following transformation. Lactose-negative transformants were isolated as white colonies on lactose-BTR-Xgal agar plates containing erythromycin. Six lactose-negative mutants representing three different chromosomal sites of integration were isolated from about eight thousand transformants. Mutant chromosomal DNA fragments flanking the plasmids were recovered by a marker-rescue method in E. coli and exhibited phospho-beta-galactosidase activity. PMID- 1624104 TI - Eukaryotic cell components that bind to chlamydial elementary bodies: the histones. AB - HeLa-cell-membrane fractions isolated by sonication as used previously to identify chlamydial adhesins were examined by a blotting technique for binding chlamydial elementary bodies (EB). One HeLa cell protein with apparent molecular mass of 32 kDa was found to bind native EB. A monoclonal antibody (mAb) raised against this chlamydial binding host-cell protein reacted with eucaryotic histones. Histone fractions were capable of binding EB in an ELISA assay and histone H1 was identified as the chlamydial-binding host cell protein in the Hela cell membrane fraction. Probing with specific mAbs against histone H3 and DNA confirmed that chromatin components were present in the host-cell membrane extract. These data suggest that the HeLa-cell-binding chlamydial proteins were previously identified by their reaction with chromatin and not with membrane components. PMID- 1624105 TI - Bioluminescent Listeria monocytogenes provide a rapid assay for measuring biocide efficacy. PMID- 1624106 TI - Physical characterisation and over-expression of the Bacillus caldotenax superoxide dismutase gene. AB - The gene (sod) encoding Bacillus caldotenax (BC) Mn-superoxide dismutase (MnSOD) has been cloned in Escherichia coli and its entire nucleotide sequence determined. Within the coding region of the gene there were 21 nucleotide differences to the previously sequenced sod of Bacillus stearothermophilus (BS). The predicted amino acid sequence of BCMnSOD had two amino acid dissimilarities to the BSMnSOD, containing Asp and Val at positions 13 and 188, respectively, compared to Glu and Ile at the respective equivalent positions of BSMnSOD. Recombinant BCMnSOD was shown to be functionally active in E. coli, both in vitro and in vivo, and was produced at levels representing over 40% of the cells' soluble protein by coupling sod transcription to the E. coli trp promoter. The sequenced region of DNA was also found to encompass part of a second open-reading frame, of unknown function, previously noted 3' to the B. stearothermophilus gene. PMID- 1624107 TI - Inactivation of a Serpula (Treponema) hyodysenteriae hemolysin gene by homologous recombination: importance of this hemolysin in pathogenesis in mice. PMID- 1624108 TI - Selection of a Borrelia burgdorferi antigenic variant by cultivation in the presence of increasing amounts of homologous immune serum. AB - This investigation was undertaken to select antigenic variants of a Borrelia burgdorferi strain in vitro. The original strain BITS was cultivated in BSK medium supplemented with increasing concentrations of homologous hyperimmune serum raised in rabbits. After a few serial passages starting from a subinhibitory serum dilution of 1:800 in BSK up to 1:200, a variant named BITSv was obtained; it grew abundantly like the control culture in the presence of hyperimmune serum. Analysis of the antigenic pattern of the original and derived variants by Western blotting revealed that BITSv, compared to the original strain BITS, had lost the reactivity with the immune serum at the level of the oligosaccharide moiety. These experiments, designed to mimic the possible action of antibodies that arise during a Borrelia infection, suggest that lipopolysaccharides are surface located and that they play a role in the integrity of the outer membrane during the multiplication of Borrelia burgdorferi. PMID- 1624109 TI - Fine-structure mapping of cis-acting control sites in the lysC operon of Bacillus subtilis. AB - Mutations at the aecA locus of Bacillus subtilis lead to derepression of the lysC operon, which encodes aspartokinase II, and analysis of three independent aecA mutations has shown them to be nucleotide substitutions in the lysC leader region (Y. Lu, N.Y. Chen and H. Paulus (1991) J. Gen. Microbiol. 137, 1135-1141). DNA sequence analysis of the lysC control region of nine other mutants with derepressed levels of aspartokinase II revealed each of the mutations to be associated with changes in one or a few nucleotide residues. The nucleotide substitutions were clustered at two sites in the lysC leader: in a region of imperfect dyad symmetry about 40 base pairs from the transcription start site, and in the open reading frame for a putative leader peptide, which starts about 40 residues further downstream. The effect of nucleotide substitutions at the two sites differed in that those at the upstream site gave twice the degree of derepression. A mutant with a small deletion in the leader peptide coding region potentially affecting RNA secondary structure also had a higher level of lysC derepression. These results suggest that the lysC leader region contains at least two cis-acting control sites that play important and perhaps independent roles in the repression of the lysC operon by lysine. PMID- 1624110 TI - Typing of toxic strains of Clostridium difficile using DNA fingerprints generated with arbitrary polymerase chain reaction primers. AB - Clostridium difficile is the causative agent for pseudomembranous colitis in humans. Toxic strains of C. difficile produce two toxins, toxin A and toxin B. A reliable and definitive method of typing the toxic strains of C. difficile is needed since nosocomial cross infection is a primary concern in hospitals and other health care facilities. A method for typing toxic strains of Clostridium difficile using arbitrary polymerase chain reaction (PCR) primers is presented in this study. The C. difficile strains were initially characterized for the toxin A genetic determinant using specific PCR primers which differentiate toxin positive from toxin negative strains. These toxic strains were then PCR typed using six arbitrary primers which generated DNA patterns that were unique for all toxic strains examined. The use of this typing scheme in clinical applications is discussed. PMID- 1624112 TI - Trypanosoma cruzi 5S rRNA genes: molecular cloning, structure and chromosomal organization. AB - To further study the ribosomal RNA genetic system in Trypanosoma cruzi, the 5S rRNA gene family was characterized. We found that this gene family is reiterated about 1600 times per diploid nuclei and is mostly organized as a tandem repeat of 481 base pairs. These gene clusters were assigned to two chromosomes of about 1500 and 1400 kilobase pairs. We found that the 5S rRNA-coding region is comprised of 120 nucleotides, and contains the well-known internal control regions of eukaryotic RNA polymerase III. The two gene-spacer regions analysed exhibit a putative signal for transcription termination and six sites homologous to the consensus sequence for the binding of transcription factor Sp1. PMID- 1624111 TI - The promoter element GTACAAG of the SGA and STA2 genes is a possible target site for repression by the STA10 gene product from Saccharomyces cerevisiae. AB - The SGA and STA2 genes that, respectively, encode the intra- and extracellular glucoamylases of Saccharomyces cerevisiae are coregulated negatively, at the level of transcription, by the STA10 gene. This finding was re-examined by determining the effects of STA10 on the expression of gene constructs containing different fragments from the SGA and STA2 promoter regions fused to the lacZ gene. Repression was observed only for promoter fragments carrying the sequence GTACAAG indicating that this element is responsible for the coregulation of SGA and STA2 by STA10. PMID- 1624113 TI - Combined influence of magnesium concentration and polymerase chain reaction specificity enhancers. PMID- 1624115 TI - Does high level production of SHV-type penicillinase confer resistance to ceftazidime in Enterobacteriaceae? AB - We report the isolation of a clinical isolate of Klebsiella pneumoniae that showed resistance to ceftazidime (MIC: 8 micrograms/ml), susceptibility to aztreonam (MIC: 2 micrograms/ml) and cefotaxime (MIC: 0.015 micrograms/ml). A synergistic effect between clavulanic acid and ceftazidime or aztreonam against this strain was also observed. The strain hyperproduced SHV-1 penicillinase (990 U/g) which is encoded by a self-transferrable plasmid of at least 150 kb. That the ceftazidime-resistance phenotype could be due to hyperproduction of SHV-1 penicillinase is supported by the study of a spontaneous ceftazidime-resistant mutant in vitro obtained from an Escherichia coli strain containing plasmid p453 encoding the SHV-1. Indeed, this mutant hyperproducing SHV-1 (2200 U/g) was resistant to ceftazidime (MIC: 16 micrograms/ml) and aztreonam (MIC: 8 micrograms/ml) but susceptible to cefotaxime (MIC: 0.03 ng/ml). Clavulanic acid showed a synergistic effect when associated with ceftazidime or aztreonam. In contrast, the hyperproduction of TEM-1 (790 U/g) did not confer a ceftazidime- and aztreonam-resistant phenotype while hyperproduction of both TEM-1 and SHV-1 increased the resistance to amoxycillin/clavulanic acid and to cephalothin. PMID- 1624114 TI - A non-covalent NH2-terminal pro-region aids the production of active aqualysin I (a thermophilic protease) without the COOH-terminal pro-sequence in Escherichia coli. AB - The precursor of aqualysin I, an extracellular protease produced by Thermus aquaticus, consists of four domains: an N-terminal signal peptide, an N-terminal pro-sequence, the protease domain and a C-terminal pro-sequence. In an Escherichia coli expression system, mature and active aqualysin I is formed by treatment at 65 degrees C and the N-pro-sequence is required for its production. Complete deletion of the C-pro-sequence did not affect the production of active aqualysin I, indicating that the C-pro-sequence is not essential. A non-covalent N-pro-region was separately synthesized from the protease domain with or without the C-pro-sequence. In this system, mature and active aqualysin I was detected only when the C-pro-sequence was deleted. PMID- 1624116 TI - Mutation of serine residue 318 in the class C beta-lactamase of Enterobacter cloacae 908R. AB - The involvement of the serine residue 318 in the specificity of a class C beta lactamase was investigated. Multiple site-directed mutants at this position were generated using a polymerase chain reaction technique. These mutants were then probed for their activity towards various beta-lactam compounds. One mutant, S318G was further purified and its physico-chemical and catalytic properties determined. It was shown that the observed minimal inhibitory concentration values of this mutant could be correlated to its kinetic properties using a 'diffusion-hydrolysis' model. However, the data showed that residue 318 has little influence on the specificity of class C beta-lactamases. PMID- 1624117 TI - Characterization of lipopolysaccharides from four Pasteurella haemolytica serotype strains: evidence for presence of sialic acid in serotypes 1 and 5. AB - Highly purified lipopolysaccharides (LPS) obtained from four strains of Pasteurella haemolytica representative of four different serotypes were studied to ascertain their overall structural elements and sugar and fatty acid compositions. SDS-PAGE analysis revealed that each LPS was of the smooth-type although they differed in migration patterns. Somewhat unusual features of these LPS included the presence of: (a) rhamnose in the core oligosaccharides of serotypes 2 and 3; and (b) sialic acid in the LPS of serotypes 1 and 5. The fatty acids, myristic, hydroxymyristic and palmitic occur in essentially equivalent amounts in each of these LPS. In addition, stearic acid was present in small amounts of serotypes 1 and 5. PMID- 1624118 TI - Virulence phenotypes of Shigella flexneri 2a avirulent mutant 24570 can be complemented by the plasmid-coded positive regulator virF gene. AB - Avirulent mutation of an opaque colony variant of Shigella flexneri 2a designated 24570 has been believed to be linked with the glpK locus of the chromosome. However, avirulent phenotypes of the 24570 strain could be complemented by the invasion plasmid-coded virF gene, a positive regulator for invasion genes. The 24570 strain had a DNA structural alteration upstream of the virF gene. PMID- 1624119 TI - Evidence for a methicillin-hydrolysing beta-lactamase in Staphylococcus aureus strains with borderline susceptibility to this drug. AB - A new beta-lactamase that hydrolyses methicillin was found in the membrane fraction of two clinical isolates of Staphylococcus aureus with borderline susceptibility to this drug. 'Methicillinase' activity was detected in renatured sodium dodecyl sulfate polyacrylamide gel electrophoretograms of staphylococcal membrane proteins. The enzyme activity appeared to be inducible and was more easily detected using penicillin G (or methicillin) rather than nitrocefin as substrate. Similar activity was not detected in the membrane fraction of a methicillin-susceptible strain. These results suggest that, in the two borderline susceptible strains, rather than a hyperproduction of the penicillinase a specific methicillin-hydrolysing activity is responsible for the borderline susceptible phenotype. PMID- 1624120 TI - Biosynthesis of glyantrypine by Aspergillus clavatus. AB - The biosynthesis of glyantrypine from radiolabelled amino acid precursors has been shown experimentally to involve anthranilic acid, tryptophan and glycine. Low values for percentage incorporation of radiolabel into glyantrypine were partly influenced by a complex array of other novel alkaloids shown by the radiolabelling experiments to be related to glyantrypine. Interpretation of radiolabel incorporation from [14C-carboxyl]-anthranilic acid into microbial metabolites seen to contain an anthranilyl moiety in various biosynthetic arrangements is discussed. The possibility of diversion of anthranilic acid from the kynurenine pathway to glyantrypine biosynthesis is recognised. PMID- 1624121 TI - Susceptibility of biofilm cells of Pseudomonas aeruginosa to bactericidal actions of whole blood and serum. AB - The planktonic and young biofilm cells (harvested on day 2) of mucoid Pseudomonas aeruginosa were susceptible to the bactericidal actions of whole blood and serum. Aging biofilms of this organism (harvested on day 7) were very resistant to the killing effect of whole blood and serum. From this study we propose that the establishment of aging biofilms may contribute to persistence of this organism in biofilm-associated infections. PMID- 1624122 TI - Auxotrophy of Pseudomonas aeruginosa in cystic fibrosis. AB - Seventy-four of 403 (18.4%) sputum isolates of Pseudomonas aeruginosa from 49 of 136 (36.0%) adults with cystic fibrosis (CF) were auxotrophic mutants. Two of 11 (18.2%) isolates of P. aeruginosa taken from patients with non-CF bronchiectasis were also auxotrophic. All 99 strains taken from non-bronchiectatic sources were prototrophic. Forty-six of 55 (83.6%) CF auxotrophs required one or more of 36 growth factors tested; the requirements for the remaining 9 isolates were not identified. Methionine was the sole factor required by 17 of 22 (77.3%) isolated which depended on a single factor. We conclude that auxotrophy is a feature of P. aeruginosa infection in cystic fibrosis. PMID- 1624123 TI - Choline transport in Fusarium graminearum A 3/5. AB - Fusarium graminearum A 3/5 possesses a high affinity system (Km = 32 +/- 8 microM; mean +/- SE) for uptake of choline, which was shown to be energy dependent and constitutive. The maximum rate of choline uptake by this system was repressed by ammonia and glucose, showing a three-fold increase in maximum activity after nitrogen (2 h) or carbon (4 h) starvation. The system was highly specific for choline with only dimethylethanolamine (Ki = 198 +/- 29 microM), betaine aldehyde (Ki = 95 +/- 14 microM) and chlorocholine (Ki = 352 +/- 40 microM) acting as competitive inhibitors. Hemicholinium-3 acted as a mixed (non competitive) inhibitor (KIES = 1.9 +/- 0.6 microM; KIE = 3.6 +/- 1.9 microM). PMID- 1624124 TI - Isolation and properties of a low molecular mass endoglucanase from Trichoderma reesei. AB - Optimal culture conditions for obtaining low molecular mass endoglucanase (EG) from culture fluids of Trichoderma reesei were determined. The purification of this unglycosylated EG in a two-step procedure is described. In contrast to most cellulases, this EG did not bind to ConA-affinity columns. The unglycosylated fraction of the culture fluid proteins was further purified by preparative isoelectric focusing. Conditions relevant to an enzyme assay for this EG were determined (pH optimum 5.8, temperature optimum 52 degrees C). PMID- 1624125 TI - Aspergillus niger G proteins: subcellular localization. AB - Aspergillus niger postmitochondrial fraction, which contains high GTPase activity and high GTP binding capacity, has been subjected to subcellular fractionation on a sucrose gradient. A cytosolic and four membranous populations have been separated according to their relative density. The main difficulty has been the characterization of the plasma membrane of the fungus. This fraction, which does not contain any typical enzyme, has been identified after iodination of the outer proteins of protoplasts from A. niger. The immunological detection has shown the occurrence of cytosolic G proteins and membranous small G proteins located not only in the plasma membrane but also in the membranes of the endoplasmic reticulum. PMID- 1624126 TI - Gallium toxicity and adaptation in Pseudomonas fluorescens. AB - When cultured in a defined citrate medium supplemented with 1 mM gallium (III) Pseudomonas fluorescens ATCC 13525 experienced a lag phase of 40 h with no apparent diminution in cellular yield. Following initial uptake of the metal ligand complex, gallium was secreted in the spent fluid. This lag phase was abolished either by inoculating the medium with gallium adapted cells or by inclusion of iron (III) (20 microM) in the growth medium. In the culture enriched with both gallium and iron (III), X-ray fluorescence spectra revealed a gradual decrease of gallium from the spent fluid as growth progressed. In a phosphate deficient medium, no cellular multiplication was observed in the presence of gallium. The inhibitory influence mediated by the trivalent metal was reversed by the addition of (20 microM) iron (III). Although bacterial growth was accompanied by an initial decrease in exocellular gallium, a marked increment in the concentration of this metal was observed in the spent fluid at stationary phase of growth. Citrate was not detected in the exocellular fluid at cessation of bacterial multiplication. Electrophoretic analyses revealed numerous variations in the cytoplasmic protein profiles of the control and metal stressed cells. Gallium induced the syntheses of polypeptides with apparent molecular masses of 89 kDa, 50 kDa, 39 kDa, 26 kDa and 12 kDa. PMID- 1624127 TI - Outer membrane components of Campylobacter hyointestinalis. AB - Outer membranes were isolated, by sodium lauryl sulphate extraction, from the American type strain, five Australian, and four English isolates of Campylobacter hyointestinalis. On SDS-PAGE examination, the protein profiles of seven strains (including the type strain) were similar, and were dominated by two major proteins of 47 and 50 kDa. Three other isolates had unique major protein profiles. The largest of these proteins was heat-modifiable in these isolates, and in the type strain. The flagellin of three isolates screened was of similar M(r) to that of Campylobacter jejuni/Campylobacter coli. The lipopolysaccharides of C. hyointestinalis isolates were heterogeneous in structure; 5/10 isolates synthesised material of M(r) value greater than that of the low M(r) C. jejuni/C. coli lipopolysaccharide. By gel excision and re-electrophoresis, it was shown that the higher M(r) materials of one isolate were not artifactual aggregates of lower M(r) species. PMID- 1624128 TI - Localization and distribution of hopanoids in membrane systems of the cyanobacterium Synechocystis PCC 6714. AB - Intracellular localization of triterpenic membrane stabilizers of the hopane series is described for the first time for a cyanobacterium. In Synechocystis PCC 6714, a bacteriohopanetetrol derivative (main compound) and diplopterol were detected in cell wall (CW) and thylakoid membrane (TM). Both hopanoids were enriched 4.5-fold and 9.0-fold in CW and outer membrane (OM) fractions, respectively, compared to TMs. PMID- 1624129 TI - Salt tolerance and glycerol accumulation of a respiration-deficient mutant isolated from the petite-negative, salt-tolerant yeast Zygosaccharomyces rouxii. AB - A respiration-deficient (RD) mutant was isolated from the petite-negative, salt tolerant yeast Zygosaccharomyces rouxii. One strain among sixteen glycerol-non utilizing mutants exhibited vigorous liberation of CO2 but no uptake of O2. Furthermore, this strain lacked cytochrome aa3 and had a reduced level of cytochrome b. The few mitochondria found in cells of this strain contained few or no cristae. Salt tolerance and intracellular accumulation of glycerol by the RD strain were almost equal to that of the wild-type strain in media containing NaCl up to 2.5 M. In media with more than 3 M NaCl, the growth of the RD mutant was retarded and the intracellular accumulation of glycerol was depressed in spite of ample production. PMID- 1624130 TI - Mitotic and polytene chromosome analysis in Dacus oleae (Diptera: Tephritidae). AB - The present study constitutes the first attempt to construct a photographic map of the polytene chromosomes of Dacus oleae, a pest of the olive tree that causes serious financial damage in all olive oil producing countries. The map was constructed by using the larval fat body cells, the chromosomes of which are representative of the polytene chromosomes of other polytene tissues. In addition, the mitotic chromosomes of brain ganglia were examined, permitting tentative correlations between mitotic and polytene elements. This investigation shows that D. oleae is suitable for cytogenetic analysis in both mitotic and polytene chromosomes, a fact that may prove very useful for obtaining more detailed genetic information on the pest's natural populations. PMID- 1624131 TI - Chromosomal synapsis and the meiotic process in male mesquite lizards, Sceloporus grammicus complex. AB - Meiosis in males of the F5 cytotype of Sceloporus grammicus was examined through the analysis of synaptonemal complexes (SCs), diakinetic (metaphase I) nuclei, and secondary spermatocytes (metaphase II configurations). These data allowed the establishment of criteria for substaging of zygonema and pachynema, morphological characterization of the SC complement, and comparison of the orientation and segregation of the autosomes and sex chromosomes. The analysis of nuclei from all stages of meiotic prophase I (leptonema through diakinesis) provided a useful means of partitioning the temporal sequence of early meiotic events. Three substages of zygonema (Z1-Z3) were established, based on the extent of synapsis of the microchromosomal and macrochromosomal elements. Synaptic initiation of the autosomes and sex chromosomes was synchronous. Two patterns of macrochromosomal synapsis were observed. Whereas synapsis of the biarmed elements was biterminal (i.e., progressing from both ends of the homologs), synapsis of the acrocentric elements was uniterminal involving only the distal (noncentromeric) ends of the homologs. Unique sex-chromosomal characteristics were not observed in S. grammicus and, therefore, the substaging of pachynema was based on subjective criteria. Examination of diakinesis--metaphase I and metaphase II configurations indicated low levels of diakinetic irregularities with balanced segregation of the autosomal bivalents and the sex-chromosomal trivalent. PMID- 1624132 TI - New equations and a method for finding nine parameter values for two alleles at one locus to study gene conversion using Ascobolus immersus. AB - A quantitative treatment is given for meiotic gene conversion with its parameters and equations for their interactions to determine allele segregation class frequencies from heterozygotes. The possible pairing of both pairs of nonsister chromatids in a bivalent at exactly the same point is included. Using sets of data from Ascobolus immersus, it is shown that values for all nine parameters for hybrid DNA models of recombination can be obtained using an iterative computer program. The accuracy of the values is estimated and the double-strand gap repair model is considered. The parameter values obtained invalidate most of the simplifications used in previous quantitative analyses of gene conversion data. They showed total bias in strand preference in asymmetric hybrid DNA formation and some bias in which type of chromatid is the invading one. There were slight differences in repair frequency between the two types of mispair and very large differences in the direction of repair. Conversion control factors had major effects on hybrid DNA formation and repair of mispairs. PMID- 1624133 TI - The sequential appearance of components of the synaptonemal complex during meiosis of the female rat. AB - This paper describes the light microscopy (LM) and electron microscopy (EM) localization of synaptonemal complex (SC) antigens in oocytes of rats. For this purpose, we used monoclonal antibodies (Mabs) that recognize components of 30 + 33, 125, and 190 kDa antigens of SCs of rat spermatocytes. The LM localization was performed by immunofluorescence and the EM localization by immunogold staining. The reaction of the Mabs with oocytes was similar to the reaction with spermatocytes, but weaker. The 30 + 33 kDa as well as the 190 kDa antigens could always be demonstrated if axial elements of the SC were present, irrespective of whether these were paired or unpaired. Thus, these antigens could be detected from leptotene--early zygotene until diplotene. The 190-kDa antigen appeared in a diffuse manner just before the appearance of the 30 + 33 kDa antigens. The 30 + 33 kDa antigens were not only detected in the axial elements of SCs but also in characteristic aggregates, which appeared in zygotene and persisted until after the SCs had disappeared. Such aggregates had rarely been observed in spermatocytes. The 125 kDa antigen was only present in the tripartite segments of SCs, at the inner edge of the lateral elements. Thus, the reaction of the Mab against the 125 kDa antigen was detectable in zygotene, pachytene, and very early diplotene. It appeared later than 30 + 33 kDa and 190 kDa antigens and it disappeared earlier. We found that several steps of the immunostaining procedure could cause variation in the intensity of the Mab reaction. PMID- 1624134 TI - Two types of mouse (Mus musculus domesticus) Y chromosomes in Quebec. AB - A Y chromosomal repetitive sequence identified two types of Y chromosomes in mice (Mus musculus domesticus) caught near Ste. Anne de Bellevue, Quebec. One type is apparently identical to the Y chromosome found in Maryland, Delaware, and California, whereas the other type is similar, but not identical, to the Y chromosome present in M.m. poschiavinus, an Alpine race of M.m. domesticus. These findings suggest that the domesticus Y chromosome is highly polymorphic and thus useful for elucidating the relationships among American and European house mouse populations. PMID- 1624135 TI - Chromosome segregation from cell hybrids. VII. Reverse segregation from karyoplast hybrids suggests control by cytoplasmic factors. AB - Using human and Chinese hamster established lines as cell parents, we constructed hamster-human cell hybrids and human cell - hamster karyoplast hybrids. The cell hybrids retained one or two sets of hamster chromosomes and lost most of the human chromosomes. The karyoplast hybrids, however, retained a full set of human chromosomes and lost most of the Chinese hamster chromosomes. This reverse segregation pattern implies that cytoplasmic factors are major determinants of the direction of chromosome segregation. PMID- 1624136 TI - Partner choice in heterologous chromosome segregation of the Y chromosome in competitive situations in the oocyte of Drosophila melanogaster. AB - Heterologous segregation of the Y chromosome and secondary non-disjunction of the X chromosomes in female meiosis of Drosophila melanogaster was investigated in ten different crosses where different constellations of translocation/inversion or translocation/translocation systems of the large autosomes were present in the female parent. It appeared that the Y chromosome always segregates from the shortest of the possible heterologous pairing partners. This may be due to size dependent mechanism of so-called 'distributive disjunction' or to the possibility that the shorter the chromosome element is, the more easily it moves in the nucleus of the oocyte. Secondary non-disjunction of the X chromosomes appeared to be lower the more possible autosomal pairing partners the Y chromosome had, suggesting that the autosomes effectively compete with the X chromosomes for pairing with the Y chromosome. An alternative explanation is that, due to interchromosomal effect on recombination, crossing over in the X chromosomes was different in different experiments. PMID- 1624137 TI - A selective method for studying primary sex chromosome non-disjunction in females and males and X-Y exchange in males of Drosophila melanogaster including a demonstration of euchromatic X-Y exchange. AB - A selective method was developed, based on negative complementation of the Abruptex alleles of the Notch locus, for studying primary sex chromosome non disjunction in females and males of Drosophila melanogaster and X-Y exchange in males. The results show that the frequency of primary non-disjunction of structurally normal X chromosomes was lower than the frequency of X-derY non disjunction in males. Double exchange between the X and the derY chromosome in the male occurs with a frequency of at least 0.091%. Single exchanges are naturally expected to occur with even higher frequency. Exchanges were interestingly at least partly of euchromatic nature. The origin of these exchanges is at least partly of gonial origin. PMID- 1624138 TI - Gene flow by immigrants into isolated recipient populations: a laboratory model using flour beetles. AB - The effectiveness of immigrants as agents of gene flow was investigated in a laboratory model, using mutant marker strains of the flour beetle, Tribolium castaneum (Herbst). We show that immigrants had an advantage over residents. The proportion of hybrid offspring (PHO), resulting from immigrant mating with residents, was higher than expected from their frequency in the parental population. This advantage was observed regardless of immigrant sex and immigrant strain. The advantage seems to result from immigrant mating advantage (although not a rare-male phenomenon) and not from better survival of hybrid offspring. However, hybrid offspring seem to be more resistant to sporozoan infection, resulting in higher PHO in sporozoan-infected cultures. PMID- 1624139 TI - On fluctuation analysis: a new, simple and efficient method for computing the expected number of mutants. AB - Fluctuation analysis, which is often used to demonstrate random mutagenesis in cell lines (and to estimate mutation rates), is based on the properties of a probability distribution known as the Luria-Delbruck distribution (and its generalizations). The two main new results reported in this paper are (i) a simple, completely general, and computationally efficient procedure for calculating probability distributions arising from fluctuation analysis and (ii) the formula for this procedure when cells in a colony have only grown for a finite number of generations after initial seeding. It is also shown that the procedure reduces to one that was developed earlier when an infinite number of generations is assumed. The derivation of the generating function of the distribution is also clarified. The results obtained should also be useful to experimentalists when only a relatively short time elapses between seeding and harvesting cultures for fluctuation analysis. PMID- 1624140 TI - Effects of increasing age on vascular responses of the in vivo femoral artery of adult beagles. AB - One of the problems associated with using random-source dogs to study in vivo vascular responses is their unknown background. Since aging is known to influence vascular responses, unknown variations in age could influence experimental results. The vast majority of aging studies examine arteries in vitro. This study was undertaken to determine if increasing age of adult beagles influences in vivo femoral artery responses to acetylcholine, norepinephrine, and nitroglycerin. Experiments were performed on three groups: young (3.2 years), middle aged (6 years), and old age (8.7 years). Femoral artery responses (change in diameter, mm) to topical application of increasing concentrations of vasoactive drugs were measured by sonomicrometry. Dose-response relationships to acetylcholine were not different between groups, except at the lowest concentration (-8 log M) where young dogs had enhanced relaxation responses. Constriction to norepinephrine and relaxation to nitroglycerin were not altered by age. Thus, in the in vivo canine femoral artery of adult beagle dogs, vascular responses are essentially unaffected by increasing age. PMID- 1624141 TI - Effect of aging on enzymatic antioxidant defenses in rat liver mitochondria. AB - Antioxidant defenses within liver mitochondria are pivotal in preventing liver damage from oxidative toxicants. In this study we determined the activities of glutathione peroxidase (GPO), superoxide dismutase (SOD) and glutathione reductase (GRD) in mitochondria from livers of variously aged Fischer 344 rats. A mixed pattern of age-associated alterations in mitochondrial antioxidant activities was observed. In male rats, GRD activity decreased in old age, whereas GPO and SOD activities increased. In female rats, GPO activity decreased with age, but SOD activity increased and GRD activity was unchanged. Age-associated decreases in antioxidant protection from mitochondrial enzymes appeared to be counterbalanced by increases in protection from other enzymes. PMID- 1624142 TI - Hyaluronic acid in progeria and the aged phenotype? AB - Hyaluronic acid (HA) is implicated in functions such as vascularity, morphogenesis, repair, and the general integrity of the extracellular matrix. Hence, it is considered possible that HA is involved in the most conspicuous features of the progeroid phenotype. However, it is not known whether the increase in HA excretion seen in progeria patients is due to a primary genetic defect or is a secondary effect due to some deeper problem. The phenomenon of 'normal' aging is suggested to have a more complex etiology and phenotype than progeria and the role of HA levels is less well-defined. PMID- 1624143 TI - The fate of the quiescent surfaces of lamellar bone. AB - Microradiographic and histologic analysis of undemineralized bone was performed in 62 subjects aged 18-97 years. Ten of these samples were also submitted to scanning electron microscopy. Besides the usual lamellar bone remodeling, all types of bone surfaces, namely both haversian and vascular canals and the endosteal and trabecular surfaces, were involved in weathering alterations of the superficial lamellae, resulting in eroded outlines, less deeply notched than the Howship lacunae and devoid of osteoclast. Present as soon as early adult life and randomly distributed, these aspects were recorded in all the bone pieces examined. These observations were consistent with the hypothesis of a particular destructive process in all the quiescent lamellar bone surfaces without osteoclast participation, termed delitescence, which could be partly responsible for age-related bone loss. PMID- 1624144 TI - Clinical correlates of sway in elderly people living at home. AB - Postural sway has been noted to increase with advancing age and to correlate with a wide variety of clinical features. The relationships between sway and various clinical features were explored in a group of elderly subjects living at home and free from neurological illness and severe incapacity. Each subject underwent a thorough physical examination and sway was measured in the anteroposterior and lateral planes with eyes open and closed using a modified Wright's ataxiameter. Vibration sense was the only clinical feature to show a consistent relationship with all 4 measurements of sway in men. Age showed only a weak and inconsistent relationship to sway in both men and women. Weak but inconsistent relationships were noted between sway and mental function, tone, passive joint movement, antidepressant and tranquilliser therapy. This suggests that dorsal column function is of prime importance in the maintenance of balance and that the previously noted increase in postural sway with advancing age may have been exaggerated by the presence of disease processes. PMID- 1624145 TI - Role of obesity in development of ischemic heart disease in elderly diabetic patients. AB - The influence of obesity on the development of ischemic heart disease (IHD) was studied in 103 diabetic patients over 65 years of age. The patients were divided into three groups on the basis of their body mass index: lean, less than 20; normal, 20-25; obese, greater than 25. The incidence of IHD was significantly (p less than 0.01) higher in the obese group than in the other groups (43.2 vs. 18.8 and 16.3%). The age, sex distribution, duration and control of diabetes mellitus, methods of diabetic therapy, and prevalence of hypertension, hyperuricemia and smoking were not significantly different in the three groups. The level of serum triglyceride was higher and that of high-density lipoprotein cholesterol (HDL-C) was lower in the obese group than in the other groups, but the prevalence of IHD was significantly higher in the obese patients without hypertriglyceridemia and/or low HDL-C than in the normal group (p less than 0.05). These results suggest that obesity is a risk factor for development of IHD in elderly diabetic patients independently of other known risk factors. PMID- 1624146 TI - Quantitative computer tomography in Alzheimer's disease: a re-evaluation. AB - This investigation addresses the question of usefulness of computer-tomographic (CT) scanning in discriminating patients with Alzheimer's disease (AD) from healthy, aged controls. Quantitative measures of brain volume loss found to be significant by other investigators as well as additional unique variables are used to discriminate 58 longitudinally studied patients meeting NINCDS-ADRDA criteria for the clinical diagnosis of probable AD from 59 controls. The sensitivity and specificity of both single CT scan parameters and multivariate models comprised of such CT parameters are explored. Reasons for diagnostic misclassification are also illuminated. PMID- 1624148 TI - Optimal number of biopsy specimens in the diagnosis of carcinoma of the oesophagus. AB - The study evaluated 48 patients with carcinoma of the oesophagus to assess the optimal number of biopsy specimens required to obtain the highest yield. Eight specimens were obtained from each patient and two specimens were placed serially in each of four vials. The first vial provided a positive diagnosis in 95.8% of cases. The addition of two more specimens (second vial) increased the yield to 97.9% and the fifth and sixth specimens increased the positive yield to 100%. There was no statistically significant difference in the yield according to the site and the type of growth. PMID- 1624147 TI - Cigarette smoking and intestinal defences. PMID- 1624149 TI - Oesophageal propulsive force and its relation to manometric pressure. AB - A fixed volume capsule incorporating a force transducer and a side hole for manometric measurements was constructed and calibrated. Simultaneous measurements of the propulsive (aboral) force and the manometric pressure (intraluminal pressure) were made at 5, 10, and 15 cm above the lower oesophageal sphincter and in response to dry and wet (5, 10, and 15 ml) swallows. The propulsive force and manometric pressure waves had a simultaneous onset and were of similar duration. Peak values of propulsive force for wet swallows increased significantly as measurements were made progressively more distally within the oesophagus and were greatest in the distal oesophagus. The association between manometric pressure and propulsive force is not strong (r = 0.61) suggesting that intraluminal pressure is a poor predictor of propulsive force and hence an unreliable measure of oesophageal 'function'. PMID- 1624150 TI - Assessment of proliferation of squamous, Barrett's and gastric mucosa in patients with columnar lined Barrett's oesophagus. AB - There is no satisfactory biomarker yet available for predicting the likelihood of premalignant changes or carcinoma developing in Barrett's or columnar lined oesophagus. In this study we have evaluated the proliferation of squamous epithelium, columnar epithelium from columnar lined oesophagus and gastric columnar epithelium from 23 Barrett's patients using positive immunoreactivity with the mouse monoclonal antibody Ki67 (which recognises an antigen associated with proliferative cells) with a view to using this parameter as a biomarker. Squamous epithelium had significantly higher Ki67 immunostaining as compared with columnar epithelium from columnar lined oesophagus (when examining the tissue with greater than 15% cells staining positive for Ki67, Fisher's exact test p = 0.004) but there was no difference found between the epithelium from the columnar lined oesophagus and gastric columnar epithelium. There was no correlation between histological inflammation and Ki67 immunoreactivity of Barrett's mucosa, and the Ki67 immunostaining of two patients with dysplasia was no different from the rest of the group. There was, however, a significant correlation between the Ki67 immunoreactivity of columnar epithelium from columnar lined oesophagus and columnar epithelium from the stomach (correlation coefficient = 0.44, p = 0.03) suggesting that epithelium from columnar lined oesophagus behaves in a similar fashion to gastric epithelium. PMID- 1624151 TI - Chemotactic activity of Helicobacter pylori sonicate for human polymorphonuclear leucocytes and monocytes. AB - The immunopathology of Helicobacter pylori associated active chronic gastritis, which is characterised by predominance of polymorphonuclear leucocyte infiltration, is largely unknown. To evaluate the role of bacterial components as inflammatory mediators ultracentrifuged sonicated preparations were made of clinical isolates of Helicobacter pylori. The crude sonicates were shown to exhibit chemotactic activity for human polymorphonuclear leucocytes and blood monocytes in a concentration dependent fashion. The potency was comparable with previously described bacterial derived cytotaxins. The cytotaxin(s) was non dialysable and completely destroyed by proteinase. Heat treatment did not decrease the chemotactic activity, but in sonicate subjected to 100 degrees C for 15 minutes all activity disappeared after dialysis suggesting the breakdown of a larger protein to small fragments that are still biological active. By ammonium sulphate precipitation at increasing concentrations the cytotaxin(s) was selectively found in 10% ammonium sulphate saturation, and by further molecular gel separation the chemotactic activity was found in the molecular size range from 25 to 35 kDa. The demonstration of a polymorphonuclear leucocyte and monocyte cytotaxin from Helicobacter pylori sonicate may help in understanding the mucosal immune response in gastric inflammatory diseases. PMID- 1624152 TI - Chronic upper abdominal pain: site and radiation in various structural and functional disorders and the effect of various foods. AB - Pain site and radiation and the effect of various foods were studied prospectively in a consecutive series of patients with chronic upper abdominal pain. Patients followed for less than one year were excluded unless peptic ulcer or abdominal malignancy had been diagnosed or laparotomy had been carried out. A total of 632 patients were eligible for the first study and 431 for the second. Gastric ulcer pain was more likely to be left hypochondrial (17%) compared with pain from duodenal ulcer (4%) or from all other conditions (5%). It was less likely to be epigastric (54%) compared with duodenal ulcer pain (75%). Oesophageal pain was more likely to be both retrosternal and epigastric (25%) compared with non-oesophageal pain (2%). Radiation to the back was more common in peptic ulcer (31%) and biliary pain (35%) compared with functional pain (20%). Pain precipitation by fatty foods was commoner in biliary disease (40%) than in duodenal ulcer (11%), peptic ulcer (9%), or non-ulcer dyspepsia (19%). Orange, alcohol, and coffee precipitated pain more frequently in duodenal ulcer (41%, 50%, and 43% respectively) than in biliary disease (17%, 0%, and 14% respectively). Chilli precipitated pain in one quarter to one half of subjects regardless of diagnosis. Approximately one tenth of all subjects avoided chilli, curry, coffee, and tea because of medical or other advice. PMID- 1624153 TI - Near infrared reflectance measurement of nitrogen faecal losses. AB - Chemical methods of measuring nitrogen in stools are complex, unpleasant, and therefore rarely performed. Recently, near infrared reflectance (NIRA) has been suggested for stool analysis. The aim of this study was to evaluate the possible application of this method in routine faecal nitrogen measurement. Nitrogen concentration and daily output were measured in the stools of 83 patients using NIRA and, for comparison, the Kjeldahl method. Nitrogen concentration and output ranged between 0.4-2.72 g% and 0.45-8.96 g/day respectively. Correlation coefficients (r), of 0.89 and 0.97 were found between the two methods for concentration and output respectively, and similar values were found in patients on enteral nutrition. Repeated measurements from the same stool collection, requiring only a few minutes, allowed homogenisation to be avoided. NIRA seems to be an easy, fast, and reliable alternative to chemical assays of nitrogen measurement in the management of patients with digestive disorders. PMID- 1624155 TI - Oral salt supplements to compensate for jejunostomy losses: comparison of sodium chloride capsules, glucose electrolyte solution, and glucose polymer electrolyte solution. AB - Six patients with jejunostomies and residual jejunal lengths of 105 to 250 cm took the same food and water each day for eight study days. In random order, three methods of salt replacement were tested, each over 48 hours, against a period without added salt. During the three test periods the patients took 120 mmol of sodium chloride daily, as salt in gelatine capsules, as an isotonic glucose electrolyte (280 mOsmol/kg; 30 kcal) solution, and as a glucose polymer (Maxijul) solution (280 mOsmol/kg; 200 kcal). The daily stomal output remained constant for each patient during the four test periods but varied between patients from 0.60 to 2.84 kg (daily intestinal fluid balance 0.74-2.61 kg). Without a salt supplement, three patients lost more sodium from the stoma than they took in by mouth (-25, -94, and -101 mmol/day) and the mean sodium balance for all six subjects was -16 mmol (range -101 to 79) daily. Extra salt was absorbed with each form of supplement (p less than 0.05); no patient with the glucose electrolyte solution (mean 96, range 0 to 226 mmol), but one patient with the glucose-polymer solution (mean 96, range -25 to 164 mmol) and two with the salt capsules (mean 66, range -8 to 145 mmol) were in negative balance. Two patients vomited with the salt capsules. There was only a small increase in energy absorption (mean 115 kcal) with the glucose polymer solution compared with the glucose electrolyte solution. A sipped glucose electrolyte solution seems to be the optimal mode of sodium replacement in patients with a high output jejunostomy. PMID- 1624154 TI - Effects of acetorphan, an enkephalinase inhibitor, on experimental and acute diarrhoea. AB - Acetorphan is an orally active inhibitor of enkephalinase (EC 3.4.24.11) with antidiarrhoeal activity in rodents apparently through protection of endogenous enkephalins and a purely antisecretory mechanism. Its antidiarrhoeal activity in man was assessed in an experimental model of cathartic induced secretory diarrhoea as well as in acute diarrhoea of presumed infectious origin. In six healthy volunteers receiving castor oil and pretreated with acetorphan or placebo in a crossover controlled trial, the drug significantly decreased the number and weight of stools passed during 24 hours. About 200 outpatients with severe acute diarrhoea (more than five stools per day) were included in a randomised double blind study of acetorphan against placebo. The significant antidiarrhoeal activity of acetorphan was established using a variety of criteria: (i) the duration of both diarrhoea and treatment were diminished; (ii) no acetorphan treated patient withdrew from the study whereas five dropped out because of worsening in the placebo group; (iii) the frequency of symptoms associated with diarrhoea--for example, abdominal pain or distension, nausea and anorexia- remaining after two weeks was nearly halved; (iv) using visual analogue scales acetorphan treatment was found more effective than placebo by both investigators and patients. There was statistically no significant difference between acetorphan and placebo in respect of side effects, particularly constipation, which often accompanies the antidiarrhoeal activity of mu opioid receptor agonists this difference is attributable to the lack of antipropulsive activity of acetorphan in man. The efficacy and tolerance of acetorphan suggest that enkephalinase inhibition may represent a novel therapeutic approach for the symptomatic management of acute secretory diarrhoea without impairing intestinal transit. PMID- 1624156 TI - Determination of a critical level of tissue oxygenation in acute intestinal ischaemia. AB - Tissue oxygen tension (PtO2) was measured using a miniaturised polarographic oxygen electrode in 134 segments of rat small intestine of varying degrees of ischaemia. Without knowledge of the PtO2 levels, the viability of each segment was scored using clinical parameters and tissue damage scored by independent histological examination. Histologically non-viable bowel had significantly impaired tissue oxygenation when compared with viable bowel (t test, p less than 0.001). Marked degrees of tissue hypoxia were frequently tolerated before major histological damage became apparent, a critical PtO2 level of 1.9 mmHg being identified. The overall accuracy rate of PtO2 measurement in the operative prediction of intestinal viability was 92.5%, which contrasts with a rate of only 57.7% for clinical criteria alone. PMID- 1624157 TI - Occurrence of large granular lymphocytes and natural killer cells in the epithelium of the gut distinguishes two different coeliac diseases. AB - In a longterm study, we have divided coeliac disease into two distinct entities (abortive and permanent) based on the occurrence of large granular lymphocytes and natural killer cells within the epithelium of the gut. The natural killer and large granular lymphocytes cells were characterised by either immunohistochemical or phase contrast microscopical procedures on the initial biopsies from 15 children with coeliac disease. They were compared with seven individuals with partial villus atrophy and eight with normal villous morphology. Although the histological findings were similar in the initial biopsies of all patients with coeliac disease, the patients with permanent coeliac disease had a significantly lower number (0.41(0.61)cells/mm2) of large granular lymphocytes and natural killer cells compared with those patients with abortive coeliac disease (11.93 (6.23) cells/mm2). Those in the permanent group developed a significantly more pronounced flat mucosa after gluten challenge or provocation compared with the abortive group and had to remain on a strict gluten free diet in contrast with those in the abortive group. Thus, the occurrence of intraepithelial large granular lymphocytes and natural killer cells characterises two distinctly different coeliac diseases. Based on our results neither the histological evaluation of the biopsy nor the utilisation of the revised European Society for Paediatric Gastroenterology and Nutrition (ESPGAN) Criteria are adequate in diagnosing the two types of coeliac disease. PMID- 1624158 TI - Peripheral blood monocyte cytokine production and acute phase response in inflammatory bowel disease. AB - Cytokines released from activated mononuclear leukocytes are involved in triggering the acute phase response and many of the inflammatory manifestations of ulcerative colitis and Crohn's disease. The ability of circulating monocytes from patients with ulcerative colitis and Crohn's disease to generate the cytokines interleukin 1 beta (IL 1 beta) and tumour necrosis factor alpha (TNF alpha), both spontaneously and in response to stimulation by lipopolysaccharide, was compared. IL 1 beta generation in response to lipopolysaccharide was significantly higher in Crohn's disease than in ulcerative colitis and normal controls, with a dramatic increase in patients with active disease. There was a significant reduction in lipopolysaccharide stimulated TNF alpha generation in ulcerative colitis patients compared with Crohn's disease and normal control subjects. IL 1 beta and TNF alpha release correlated significantly with serum C reactive protein and serum alpha 1 acid glycoprotein in Crohn's disease. The ability of conditioned medium from monocytes in Crohn's disease to enhance release of alpha 1 acid glycoprotein from the liver cell line HepG2 in culture was assessed. There was a significant positive correlation between TNF alpha and IL 1 beta presence in the supernatant and alpha 1 acid glycoprotein production. The differences in the cytokine profile in patients with Crohn's disease compared with ulcerative colitis suggest an intrinsic difference in the ability to produce cytokines in patients with these two forms of inflammatory bowel disease, and may explain features such as the enhanced ability to generate a brisk C reactive protein response in Crohn's disease. PMID- 1624159 TI - Smoking in Crohn's disease: effect on localisation and clinical course. AB - The effects of smoking on the localisation and clinical course of Crohn's disease is evaluated in 231 patients. Heavy smokers (greater than 10 cigarettes/day) had an increased risk of operation at least once--odds ratios for heavy smokers compared with never smokers after five and 10 years were 1.14 and 1.24 respectively (p = 0.03 and p = 0.017). The risk of further operations was even higher and after 10 years the odds ratio was 1.79 (p = 0.015). The accumulated number of fistulae and/or abscesses was higher for smokers than for never smokers (p = 0.046). Patients with a high life time tobacco exposure (greater than 150 cigarette years) and heavy smokers (greater than 10 cigarettes/day) had small bowel disease more often than patients with lower life time exposure (less than or equal to 150 cigarette years) and patients smoking less than or equal to 10 cigarettes/day (p = 0.002 and p = 0.045 respectively). The course of Crohn's disease analysed in different ways was unfavourable for smokers, especially heavy smokers. Patients with Crohn's disease should be dissuaded from smoking. PMID- 1624160 TI - Evolution of hereditary non-polyposis colorectal cancer. AB - The prevalence of colorectal adenoma in 23 affected patients with hereditary non polyposis colorectal cancer (HNPCC) was compared with that in an age matched forensic autopsy population. The mean ages at diagnosis of colorectal cancer in men (13) and women (10) were 39 and 37 years respectively. In HNPCC patients who presented below the age of 50 years, at least one adenoma was found in 3 of 10 (30%) men and in 4 of 9 (44%) women. In the age matched autopsy specimens of large bowel, a solitary adenoma was found in 2/42 (5%) men (p = 0.015) and 1/21 (5%) women (p = 0.0075). Of the 11 adenomas from HNPCC patients, nine were greater than 1 cm and six showed a pure villous architecture. Contiguous adenocarcinoma was observed with six adenomas. Adenomas do not occur in large numbers in HNPCC, but develop at a young age, attain a large size, often show a villous configuration, and are more prone to malignant conversion than sporadic adenomas. PMID- 1624161 TI - Families at risk of colorectal cancer: who are they? AB - The first degree kinships of 305 index cases have been studied to determine whether an early age of onset or a particular site distribution characterizes familial aggregations of colorectal cancer. The probands comprised 100 patients aged 55-74 years and 205 patients under 55 years at diagnosis and were drawn from a large population database. Ascertainment and verification were complete for 2566 of 2657 first degree relatives. The history of cancer in 296 relatives was validated in 96% of cases from medical or other records. Among kinships ascertained through index cases under 55 years of age, less than 5% had three or more individuals affected by colorectal cancer. The comparable proportion of older probands' families was 3%. Probands with proximal disease were no more likely to have a positive family history of bowel cancer than those with disease distal to the splenic flexure. These findings are consistent with other population based studies of the epidemiology of familial colorectal cancer but contrast with reviews from referral centres and family cancer clinics. PMID- 1624162 TI - Effect of electrohydraulic and extracorporeal shock waves on gastrointestinal cancer cells and their response to cytotoxic agents. AB - Electrohydraulic and extracorporeal shock waves were used to treat the colorectal and gastric cancer cell lines LIM 2412 and MKN45. The effect on viability, cell proliferation, and the action of antitumour drugs was studied. Results showed that electrohydraulic and extracorporeal shock waves were cytotoxic to all cell lines and also caused considerable inhibition of cell proliferation. A significant additional reduction in cell viability was achieved by shock waves in cancer cells treated with methotrexate, 5-fluorouracil, and vincristine. These data indicate that shock waves may be worthy of further evaluation in the treatment of gastrointestinal cancers. PMID- 1624163 TI - Mucosal immune defence mechanisms in enterocolitis complicating Hirschsprung's disease. AB - Enterocolitis remains an important cause of morbidity and mortality in Hirschsprung's disease. The aetiology of enterocolitis is uncertain-ischaemic and bacterial causes and recently, rotavirus infections, have been suggested. Bowel tissue from 12 patients with Hirschsprung's disease who underwent Swenson's operation (five of whom had clinical evidence of enterocolitis) and colon from six controls subjects were examined to investigate possible immunopathological mechanisms associated with the disease. IgA, IgM, and J chain (but not IgG) containing plasma cells were significantly increased in the lamina propria along the entire length of resected bowel in enterocolitis patients, compared with non enterocolitis patients and controls (p less than 0.01). Luminal secretory component staining of the anganglionic segment of colon from enterocolitis patients was considerably reduced. Lamina propria CD68 positive monocyte/macrophages and CD45RO positive leukocytes were increased in enterocolitis patients compared with non-enterocolitis patients (p less than 0.01). CD57 positive natural killer (NK) cells showed a unique distribution pattern compared with other cell types. Patients with enterocolitis showed a significant increase in CD57 positive NK cells in the lamina propria of ganglionic bowel only (p less than 0.05). NK cell values in ganglionic bowel of non-enterocolitis patients and in aganglionic bowel in all patients were similar to controls. The diversity of altered local immune response seen in this study may reflect a multifactorial microbial aetiology in enterocolitis associated with Hirschsprung's disease. PMID- 1624164 TI - Utility of a combined test of anorectal manometry, electromyography, and sensation in determining the mechanism of 'idiopathic' faecal incontinence. AB - Combined tests of anorectal manometry, sphincter electromyography and rectal sensation were carried out in 302 patients with faecal incontinence (235 women, 67 men). The results obtained were compared with 65 normal subjects (35 women, 30 men). A mechanism for incontinence was identified in all and the majority of patients had more than one abnormality. Two hundred and seventy eight patients (92%) had a weak external anal sphincter, 185 of these (67%, mostly women) also showed abnormal perineal descent, and 14 women showed clinical evidence of sphincter damage as a result of obstetric trauma. Ten per cent of patients with impaired external anal sphincter contraction showed associated evidence of spinal disease (impaired rectal sensation plus attenuated or enhanced reflex external anal sphincter activity). Unlike the other groups, the 'spinal' group contained equal numbers of men and women. Ninety seven patients (32%) had evidence of a weak internal anal sphincter. The external sphincter was also very weak and 92% of these patients also had perineal descent. Eighty two patients (27%) showed an unstable internal sphincter, characterised by prolonged 'spontaneous' anal relaxation under resting conditions and an abnormal reduction in anal pressure after conscious contraction of the sphincter or an increase in intraabdominal pressure. One hundred and forty two patients (47%) had a hypersensitive rectum associated with enhanced anorectal responses to rectal distension. All these patients had an abnormally weak external sphincter, suggesting that the hypersensitive or 'irritable' rectum should not be regarded as a cause of faecal incontinence unless accompanied by external sphincter weakness. Twenty four patients (8%) showed a normal basal and squeeze pressures and impaired rectal sensation; six showed giant rectal contractions during rectal distension. The results show that idiopathic faecal incontinence is not caused by a single abnormality, and it is suggested that combined anorectal manometry, electromyography, and sensory testing is a useful technique to identify the causes of faecal incontinence and provide a basis for appropriate treatment. PMID- 1624165 TI - Relation between hysterectomy and the irritable bowel: a prospective study. AB - Some women with irritable bowel syndrome date the onset of symptoms to previous hysterectomy. To assess prospectively the incidence of gastrointestinal symptomatology arising de novo after hysterectomy, and to study the effect of surgery on pre-existing symptoms, 205 women completed a symptom questionnaire before and six weeks and six months after surgery. Beforehand, symptoms suggestive of irritable bowel syndrome occurred in 22% of patients. At six months after operation, 60% of these had improved or were symptom free while 20% had increased symptomatology. New gastrointestinal symptoms were present more than once per week in 10% of previously asymptomatic women. Constipation predominant irritable bowel syndrome was the commonest symptom complex seen de novo, occurring more than once per week in 5% of the group. No relation was found between new symptomatology and the type of hysterectomy, oophorectomy, or the administration of perioperative antibiotics. This study suggests that many women with pre-existing gastrointestinal symptomatology improve after hysterectomy. However, symptoms suggestive of irritable bowel syndrome do arise de novo in 10%. As hysterectomy is common, gastroenterologists can expect to see women presenting with post-hysterectomy problems. PMID- 1624166 TI - Defecation frequency and timing, and stool form in the general population: a prospective study. AB - Because the range of bowel habits and stool types in the community is unknown we questioned 838 men and 1059 women, comprising 72.2% of a random stratified sample of the East Bristol population. Most of them kept records of three consecutive defecations, including stool form on a validated six point scale ranging from hard, round lumps to mushy. Questionnaire responses agreed moderately well with recorded data. Although the most common bowel habit was once daily this was a minority practice in both sexes; a regular 24 hour cycle was apparent in only 40% of men and 33% of women. Another 7% of men and 4% of women seemed to have a regular twice or thrice daily bowel habit. Thus most people had irregular bowels. A third of women defecated less often than daily and 1% once a week or less. Stools at the constipated end of the scale were passed more often by women than men. In women of child bearing age bowel habit and the spectrum of stool types were shifted towards constipation and irregularity compared with older women and three cases of severe slow transit constipation were discovered in young women. Otherwise age had little effect on bowel habit or stool type. Normal stool types, defined as those least likely to evoke symptoms, accounted for only 56% of all stools in women and 61% in men. Most defecations occurred in the early morning and earlier in men than in women. We conclude that conventionally normal bowel function is enjoyed by less than half the population and that, in this aspect of human physiology, younger women are especially disadvantaged. PMID- 1624167 TI - Effects of stressful life events on bowel symptoms: subjects with irritable bowel syndrome compared with subjects without bowel dysfunction. AB - A standardised inventory of stressful life events and a bowel symptom questionnaire were administered at three month intervals for one year to 383 women who were unselected with respect to bowel symptoms. A NEO Personality Inventory was given initially to assess neuroticism. Subjects who satisfied restrictive diagnostic criteria for irritable bowel syndrome were compared with those who complained of abdominal pain plus altered bowel habits but who did not meet restrictive diagnostic criteria (functional bowel disorder) and with controls without bowel dysfunction. The irritable bowel group showed significantly higher levels of stress than the other two groups even when the confounding effects of neuroticism were statistically controlled for. Time lagged correlations showed that stress in one three month interval was significantly correlated with bowel symptoms in the subsequent three month interval for all groups. The slope of the regression line relating stress to bowel symptoms was significantly steeper for the irritable bowel group than for the other two groups at three and six months, suggesting that subjects with irritable bowel syndrome show a greater reactivity to stress. Stress scores were also significantly correlated with the number of disability days and the number of medical clinic visits for bowel symptoms. PMID- 1624168 TI - Effect of in vivo administration of an antibody to epidermal growth factor on the rapid increase in DNA synthesis induced by partial hepatectomy in the rat. AB - Recent reports indicate that transforming growth factor alpha (TGF-alpha) is produced within the liver and acts as the natural ligand of the epidermal growth factor (EGF) receptor causing the EGF receptor down regulation and the hepatocyte proliferation observed after partial hepatectomy. The reported phenomenon that an antibody to EGF inhibits the regenerative response to partial hepatectomy was therefore re-investigated. The IgG fraction of an anti-rat EGF antibody was injected intravenously at the time of partial hepatectomy, and its effects on regenerative DNA synthesis were compared with those of non-immune IgG. Injection of IgG reduced the DNA synthetic response to partial hepatectomy, assessed 24 hours after resection by 3H-thymidine incorporation, but the effects of normal and anti-EGF IgG were not statistically different, despite the presence of excess anti-EGF IgG in the circulation throughout the experimental period. However, anti EGF IgG could completely block the proliferative response of hepatocytes in culture to EGF. These results support the suggestion that EGF is not the major mediator of hepatocyte DNA synthesis in the early stages of liver regeneration (less than 24 hours). PMID- 1624169 TI - Aminopyrine breath test in the prognostic evaluation of patients with cirrhosis. AB - This prospective study assessed the role of aminopyrine breath test in the prognosis of patients with cirrhosis, and evaluated whether the test provided useful information not included in the Pugh score. During a period of 36 months, 125 patients with biopsy proven liver cirrhosis were included, and followed for up to 48 months (median 17 months). During follow up 43 patients died (20 of liver failure). Survival was univariately related to aminopyrine breath test (p less than 0.02), Pugh score (p less than 0.01), presence of ascites (p less than 0.01), and sex (p less than 0.05). Using Cox's regression analysis, Pugh score, aminopyrine breath test, and sex, were independent significant predictors of survival. From the Cox's model a prognostic index was computed. According to a receiver operating characteristic curve analysis, the prognostic index predicting death showed an improvement in area under the curve when compared with a prognostic index calculated excluding aminopyrine breath test, but the improvement did not reach statistical significance (p = 0.12). A similar prognostic index was calculated to predict death from liver failure. Cox's regression analysis selected aminopyrine breath test, Pugh score, and aetiology as the best set of predictor covariates. According to a receiver operating characteristic curve analysis, a prognostic index cut off value of 2.6 had a 94% sensitivity and a 88% specificity. The prognostic index significantly improved prognostic accuracy when compared with a prognostic index calculated from Pugh score and aetiology, but excluding aminopyrine breath test (p = 0.05). These data disclose that the aminopyrine breath test offers additional prognostic information to the Pugh score, and the prognosis of patients with cirrhosis. PMID- 1624170 TI - Pancreatic surgery, not pancreatitis, is the primary cause of diabetes after acute fulminant pancreatitis. AB - Acute fulminant pancreatitis is associated with significant morbidity and mortality. To examine the outcome of conservative and surgical treatment of this disorder, 36 patients who survived an initial episode were restudied after a mean of six years. Fifty three per cent had developed diabetes mellitus, half of whom required insulin therapy. Pancreatic resection was associated with a 100% frequency of diabetes, while only 26% of those treated with peritoneal lavage developed this (p less than 0.001). Insulin secretion and sensitivity were assessed using the hyperglycaemic glucose clamp technique. First phase insulin secretion was impaired in surgically treated patients (mean (SEM) 14 (5) microU/ml x 10 minutes) compared with conservatively treated patients and control subjects (144 (66) and 87 (12) microU/ml x 10 minutes, respectively; p less than 0.05). Second phase and 'maximal' insulin secretion were also impaired among the surgically treated patients compared with the conservatively treated patients and the controls. Insulin sensitivity was reduced among the surgically treated patients (2.88 (58) mg/kg.minute) when compared with conservatively treated patients and healthy control subjects (5.87 (1.02) and 6.45 (0.66) mg/kg.minute; p less than 0.05). Pancreatic resection is associated with a very high frequency of diabetes compared with peritoneal lavage, and these results favour conservative treatment of active fulminant pancreatitis whenever possible. PMID- 1624171 TI - Glycine nitrogen in total parenteral nutrition: two prospective clinical trials comparing the efficacy of high and low glycine containing amino acid solutions. AB - Glycine has been regarded as a poor source of nitrogen for total parenteral nutrition. Two prospective randomised cross over controlled clinical trials were undertaken to compare the efficacy of high and low glycine containing amino acid solutions in parenterally fed malnourished hypoalbuminaemic patients with gastrointestinal disease. In the first study (n = 9), amino acid solutions in which glycine accounted for 23% and 4% of total nitrogen were compared. No statistically significant difference was found in urea nitrogen/total urinary nitrogen excretion (mean (SEM) 83.4 (1.4) v 81.6 (1.7)%, p = 0.31), nitrogen balance (-1.9 (2.4) v -0.6 (2.0) g/day, p = 0.31) or plasma protein concentrations and blood urea nitrogen. In the second extended study (n = 5), there was no significant difference in net whole body protein synthesis (+1.3 (4.7) v-0.2 (3.7) mg/kg/hour, p = 0.69) or fractional (0.403 (0.070) v 0.480 (0.41)%/hour, p = 0.68) and absolute albumin synthesis rates (6.0 (0.9) v 7.2 (0.06) mg/kg/hour, p = 0.22), on comparing solutions of 25% and 8% glycine nitrogen. In addition, a significantly higher proportion of total urinary nitrogen comprised urea when patients received the low glycine containing amino acid source (81.4 (2.5) v 83.8 (3.2)%, p = 0.04). It is concluded that there are no apparent short term nutritional or metabolic disadvantages to using amino acid solutions that contain up to 25% of nitrogen as glycine in total parenteral nutrition. PMID- 1624172 TI - Sustained hypothyroidism induced by recombinant alpha interferon in patients with chronic hepatitis C. AB - Thyroid dysfunction has been reported in patients with malignant disease treated with recombinant alpha interferon. Two cases of hypothyroidism in patients with chronic hepatitis C treated with recombinant alpha interferon are reported. In one patient, interferon induced hypothyroidism in the absence of pre-existing thyroid dysfunction and in the other it aggravated a pre-existing thyroid dysfunction. Both patients developed a severe, sustained hypothyroidism requiring thyroxine treatment for one year or more after stopping alpha interferon. Diagnosis of hypothyroidism during treatment can be difficult because of the common side effects of alpha interferon. Thyroid function should be assessed before and during alpha interferon therapy in patients with chronic hepatitis C. PMID- 1624173 TI - Thrombotic thrombocytopenic purpura mimicking acute small bowel Crohn's disease. AB - A 39 year old woman presented with a short history of bloody diarrhoea. She subsequently developed microangiopathic haemolysis, platelet consumption, and renal impairment. Initial investigations suggested underlying Crohn's disease of the terminal ileum complicated by sepsis and disseminated intravascular coagulation. However, after resection of a perforated caecum and terminal ileum, the diagnosis of thrombotic thrombocytopenic purpura was made. There was weak serological evidence of yersinia infection, this may have caused the early localisation of the lesions to the terminal ileum. This is believed to be the first report of thrombotic thrombocytopenic purpura affecting the small bowel alone at presentation. PMID- 1624174 TI - Oesophageal candidiasis after omeprazole therapy. AB - Oesophageal candidiasis was diagnosed incidentally at endoscopy in two patients receiving omeprazole therapy. There were no other predisposing factors for the development of candidiasis. The infection was resolved rapidly by anti-candidal therapy and by stopping omeprazole. These findings suggest that gastric acid secretion and physiological reflux of acid into the oesophagus may play a protective role in preventing candida infection. PMID- 1624175 TI - Adenocarcinoma and Barrett's oesophagus. PMID- 1624177 TI - [Proceedings of the Regional Meetings of the Italian Society of Hematology. Abstracts]. PMID- 1624176 TI - Omeprazole versus ranitidine in the treatment of resistant duodenal ulcer. PMID- 1624178 TI - Preventing lead poisoning. PMID- 1624179 TI - Safety and health in the health care setting. PMID- 1624180 TI - Bottled water--consumers beware. PMID- 1624181 TI - A greener workplace at NH Hospital: a model for environmental action. PMID- 1624182 TI - MedCycle offers waste strategies for hospitals. PMID- 1624183 TI - HIV transmission in the environment: risks to public health. PMID- 1624184 TI - Potential hazards with protective restraint devices. PMID- 1624185 TI - Investigations into the fat pads of the sole of the foot: heel pressure studies. AB - The fat pads of the heel have a structure that is optimized for load bearing. In various diseases and aging, the load-carrying ability of the heel pad is clinically impaired. The loading pattern was examined in subjects having normal heel pads and those with atrophic heel pads, both with and without clinical symptoms. Normal heel pads showed a broad region of high pressure, which accounted for a high percentage of the total load transmission. In contrast, the atrophic heels showed a high but narrow peak pressure. However, most of the load was transmitted over a large area of low pressure. There was no difference between symptomatic and asymptomatic heels. The mechanical behavior of the fat pad is discussed with particular reference to the anatomic structure of the pads. Pad thickness and septal integrity are both important to the mechanical characteristics of the fat pad. The load-bearing patterns observed are discussed in terms of the mechanical components influencing fat pad resilience. These results have direct relevance to understanding the pathophysiology of heel pain secondary to degeneration of the fat pad. PMID- 1624186 TI - Investigations into the fat pads of the sole of the foot: anatomy and histology. AB - Anatomical, histological, and histochemical studies were performed on normal and abnormal fat pads of the sole of cadaver feet. The fat pads were found to contain a significant nerve and blood supply separate from that to the surrounding musculature and skin. Pacinian corpuscles and free nerve endings within the fat were identified. Histological analysis indicated a meshwork of fibroelastic septae arranged in a closed-cell configuration. The mechanical consequences of this organization are discussed in the context of the weightbearing role of the fat pads of the feet. Alterations seen in dysvascular or senescent feet are consistent with the hypothesis that the septal anatomy of the fat pads is central to their cushioning function. PMID- 1624187 TI - Salvage of failed first metatarsophalangeal joint implant arthroplasty by implant removal and synovectomy: clinical and biomechanical evaluation. AB - Implant removal and synovectomy were used to treat the failure of 14 first metatarsophalangeal joint implant arthroplasties. Revision surgery was performed at an average of 3.1 years after arthroplasty. Follow-up (average 4.9 years) was possible in 10 patients, and clinical results were excellent in seven patients, good in one patient, fair in one patient, and poor in one patient. No significant changes in alignment occurred, although a trend toward toe extension was noted. Dynamic force plate studies in these patients demonstrated less pressure under the first metatarsal head and greater loading under the lateral forefoot. The great toe had less contact time during gait in the involved feet than in the control feet. PMID- 1624188 TI - Talocalcaneal coalition: diagnosis and surgical management. AB - The authors studied 22 patients who had 32 feet with symptomatic talocalcaneal coalition. All feet were treated with excision of the bar and interposition of an autogenous free fat graft. These cases were assessed clinically and radiographically before and after the operation. They conclude that this technique is a good surgery with gratifying results. In the final outcome, 78.1% of feet became completely painless and 21.8% achieved relief of pain. There was improvement of the deformity in 68.7% and of range of motion in 75%. PMID- 1624189 TI - The art and science of fitting shoes. AB - The two primary components of achieving proper shoe fit are shoe shape and shoe size. Shoe shape refers to the shape of both the sole and the upper. Proper fit is achieved when shoe shape is matched to foot shape. Shoe size is determined by arch length rather than overall foot length. The proper shoe size is the one that accommodates the first metatarsal joint in the widest part of the shoe. A set of seven guidelines for achieving proper shoe fit is offered. Properly fitting shoes are important in avoiding foot discomfort and deformity, and are absolutely essential in patients with arthritis, diabetes, and other foot disorders. PMID- 1624190 TI - A method for measuring foot pressures using a high resolution, computerized insole sensor: the effect of heel wedges on plantar pressure distribution and center of force. AB - A new, high resolution, pressure-sensitive insole was tested and found to provide reproducible measurements of static and dynamic plantar pressures inside the shoe of normal test subjects under certain conditions. However, calibration between separate sensors was poor and the sensor pads showed significant wear with use. This system was also used to investigate the effect of heel wedges on plantar foot pressure to determine whether this system was sensitive enough to detect the effect of a gross shoe modification on plantar foot pressure. Medial heel wedges decreased plantar pressures under the first and second metatarsals as well as under the first toe, and shifted the center of force laterally in all portions of the foot. Lateral heel wedges decreased pressures under the third, fourth, and fifth metatarsals, increased pressures under the first and second metatarsals, and shifted the center of force medially in all portions of the foot. Our evaluations indicate that it is possible to measure static and dynamic plantar foot pressures within shoes and to study the possible effect of shoe modifications on plantar pressures in controlled gait trials. PMID- 1624191 TI - Transcutaneous oxygen as a predictor of wound healing in amputations of the foot and ankle. AB - Thirty-eight amputations of the foot and ankle were performed in patients with peripheral vascular insufficiency over a 20-month period. Amputation level selection was based on clinical examination, a minimum ankle-brachial index of 0.5 as a measure of vascular supply, serum albumin of 3.0 gm/dl as a measure of tissue nutrition, and a total lymphocyte count of 1500 as a measure of immunocompetence. Transcutaneous oxygen tension was measured at the midfoot and ankle levels prior to surgery. Thirty-two of 38 patients (84.2%) healed their amputation wounds. When the transcutaneous oxygen tension was greater than 30 mm Hg, 24 of 26 patients (92.3%) healed. When the value was below 30 mm Hg, only eight of 12 patients healed. When the propensity to support wound healing is factored out, with patients having the metabolic capacity to heal an amputation wound in the foot and ankle, it appears that transcutaneous oxygen tension is an accurate measure of vascular inflow to support amputation wound healing. PMID- 1624192 TI - Silicone lymphadenopathy associated with failed prosthesis of the hallux: a case report and literature review. AB - Three years after replacement of a first metatarsophalangeal joint with a silicone prosthesis, a tennis player developed an enlarged ipsilateral femoral lymph node. The implant was also noted to have failed. Fine needle aspiration of the node revealed a foreign body giant cell reaction to particulates morphologically compatible with silicone elastomer. This finding suggests the potential utility of fine needle aspiration in the evaluation of patient response to foreign materials used in prosthetic devices. The lymphadenopathy also suggests that prosthetic metatarsophalangeal replacement in patients with high demand activities run the risk not only of failure of the prosthesis, but also of central migration of the particulate debris resulting from silicone elastomers. PMID- 1624193 TI - Excision of the fractured os peroneum: a report on five patients and review of the literature. AB - Five patients sustained fractures of the os peroneum after supination and plantarflexion injuries. Two of the injuries involved the knee in hyperflexion and the foot under the buttock. Four of the five were treated with immobilization for 6 weeks. All five required operative excision of the fractured sesamoid 8 months to 8 years after the initial injury. Three fractures were bipartite and there were two multipartite fractures. At 12- to 28-month follow-up, all patients were pain-free over the lateral midfoot and four patients returned to preinjury activity levels. PMID- 1624194 TI - Regional anesthesia for foot and ankle surgery. AB - We present our experience with the use of regional anesthesia in 1295 of 1862 (69.5%) surgical procedures of the foot and ankle between 1986 and 1989. Regional anesthesia was used for surgical procedures of the forefoot, midfoot, hindfoot, and ankle in the setting of elective surgery and trauma. From the viewpoint of the surgeon, regional anesthesia was completely successful in 95% of the procedures performed. Sample patient surveys confirmed that 87% of patients were satisfied with the use of regional anesthesia for their operative procedure. There were four (0.3%) minor complications, one being lidocaine toxicity. With increasing experience, the expanded indications and uses of regional anesthesia for foot and ankle surgery are proving to be simple, safe, reliable, and well tolerated by the patient. PMID- 1624195 TI - [Differential therapy with calcium antagonists]. PMID- 1624196 TI - [Basic therapy of bronchial asthma. Evaluation of therapeutic alternatives: dosing aerosols, powder inhalation systems, nebulizers. Conference proceedings. Frankfurt-Gravenbruch, 13-14 March 1992]. PMID- 1624197 TI - Progression of periodontal pockets in the age cohort 35-44 years. AB - In 1985 the Health Department of the Italian Telephone Company decided to launch an oral health programme for all its employees and their relatives, with the collaboration of the WHO Collaborating Centre of the Clinica Odontoiatrica Ospedale S. Paolo, Milan. The programme started with an epidemiological survey of dental and periodontal condition; following data analysis, the company also contracted with private dentists to provide oral care. Four years later, in 1989, several studies were set up to evaluate the programme. The WHO Collaborating Centre Milan was requested to evaluate the periodontal care given to a sample of persons living in the Milan area. Seventy-seven individuals with established periodontal lesions were selected out of a group of 678 aged between 35 and 44 years examined in 1985. The same periodontal and dental indices used in 1985, CPITN (Community Periodontal Index of Treatment Needs) and DMFT (decayed, missing, filled teeth), were re-evaluated in these 77 persons and information about any periodontal care since 1985 was collected and checked against the reimbursement records of the Telephone Company. There was an increase in the percentage of persons with deep pockets (from 55.8 to 72.7 per cent), and of the mean of sextants affected (from 0.9 to 1.9). These individuals had been treated for dental problems, as demonstrated by an increase in the F component and a reduction of the D component of the DMFT, but had undergone virtually no treatment for periodontal problems. This may be considered as a longitudinal study on the natural progression of periodontal pathology in individuals with established periodontal lesions. PMID- 1624199 TI - The Swedish patient insurance scheme and guarantee insurance for prosthodontic treatment. AB - During 1975-76 a no-fault compensation system for treatment injuries in dentistry and failures within prosthodontics was introduced in Sweden. The guarantee insurance scheme for prosthetic treatment has changed somewhat during the years and, in 1987, became mandatory for all dentists in Sweden. All necessary retreatment not included in the National Dental Insurance Scheme (eg allergy to dental materials, all treatment following radiotherapy-related xerostomia) is included. For fixed prosthodontics, all replacements are covered by the scheme for the first 2 years. For removable prosthodontics, this is limited to the first year. A patient may choose any dentist in Sweden to carry out the retreatment. The claim system is simple and the number of cases has steadily increased, probably because dentists are becoming more familiar with the system and are willing to use it. The costs are paid for by private practitioners, the Public Dental Service and private dental laboratories. The insurance files are available for research purposes. PMID- 1624198 TI - The biological effects of fluoride on tooth development: possible use of cell culture systems. AB - The action of fluoride on tooth development and the observed side-effects of fluorosis are not yet fully understood. The authors briefly review the literature relating to hypotheses on dental fluorosis and describe in vitro cell culture techniques which could help to clarify the biological effect of fluoride on dental pulpal cells. PMID- 1624200 TI - Fear of amalgam: dentists' experiences in the Nordic countries. AB - The purpose of the present investigation was to study Nordic dentists' experiences with patients concerned about the possible adverse effects of dental restorations, their perceived ability to deal with this problem and their views as to the suitability of amalgam as a filling material. A random sample of practising dentists in Denmark, Finland, Norway and Sweden were sent a questionnaire in spring 1990. Responses were received from 1732 dentists (65 per cent). In 1989, virtually every dentist had seen patients concerned about possible adverse effects of their dental restorations. The reported mean number of such patients per dentist per year was 80.5 (SD = 128.1) in Denmark, 39.3 (SD = 68.4) in Finland, 83.3 (SD = 194.1) in Norway, and 124.4 (SD = 210.3) in Sweden. Ninety-two per cent of the patients' questions concerned amalgam fillings. About 70 per cent of the dentists believed that inexplicable symptoms associated with amalgam fillings had a psychosomatic background. Only about a fifth of the respondents felt able to examine such patients without seeking medical expertise. In the absence of oral or medical indications, 65 per cent of the respondents in Sweden and 77 per cent in the other countries considered that dentists should advise patients against having their amalgam fillings replaced. About 5 per cent of the respondents were ready to stop using amalgam in the near future. PMID- 1624201 TI - New attachment and tissue regeneration. AB - In periodontology, the possibility of stimulating new connective tissue attachment to previously diseased root surfaces, and the regeneration of the supporting periodontal tissues destroyed by periodontitis have been under study for some years. This paper reviews the different experimental methods used to prepare root surfaces for optimal regeneration and attachment of periodontal tissues. The mechanisms of blood clot formation, adhesion to the root surface and wound maturation are considered, as are the future needs for research in this subject. PMID- 1624202 TI - The effectiveness of the newly designed 'Concept 45 degrees' toothbrush for removal of dental plaque in primary schoolchildren. AB - A single-blind, two-period cross-over study involving 36 primary schoolchildren, grade 6, aged 11-12 years, was conducted to evaluate the effectiveness of the newly designed 'Concept 45 degrees' toothbrush. This toothbrush, with straight, multi-tufted bristles and a specially designed handle, was compared with a control toothbrush with straight, multi-tufted bristles and a conventionally designed handle for removing dental plaque. All subjects were instructed to brush their teeth using the Bass technique. The subjects were asked to refrain from brushing for 24 hours before the study, to provide an indication of which subjects had the greatest potential for plaque development. Dental plaque was scored before and after brushing for 2 minutes. Results indicated that the use of the 'Concept 45 degrees' toothbrush removed significantly more dental plaque when compared to a standard, conventional toothbrush. PMID- 1624203 TI - Prevention as a treatment of excellence--a view from Mexico City. AB - Using survey data from Mexico City recorded in 1982 and 1989, the results of this paper suggest that practice-based, disease-orientated, one-to-one technical dentistry is failing to solve the problems of oral health. Prevention constitutes a much better alternative as it can be provided for a greater number of people, more easily and more cheaply. Recommendations are made on how dental practitioners can adopt measures to change professional behaviour in order to institute preventive measures. PMID- 1624204 TI - Periodontal treatment needs, by CPITN, among employees of a Jerusalem hospital. AB - A survey, employing the Community Periodontal Index of Treatment Needs (CPITN), was conducted among 344 employees of a Jerusalem hospital. Of the population surveyed, 2.2 per cent demonstrated totally healthy mouths, 1.5 per cent had, at the worst, bleeding symptoms, 13.3 per cent had calculus, 53.4 per cent had 4-5 mm ('shallow' according to WHO) pockets and 29.6 per cent had deep pockets (6 mm or more) as their worst CPITN scores. Results revealed an average of 0.55 edentulous sextants, 0.68 healthy sextants, 0.87 sextants with bleeding symptoms, 1.36 with calculus, 1.95 with 4-5 mm pockets and 0.61 sextants with deep pockets. In general, females were healthier than males, had a significantly greater number of healthy sextants, less sextants with calculus and less sextants with deep pockets. A deterioration in periodontal health with age was evident, according to mean number of sextants per person by CPITN scores. Associations were also analysed between CPITN and demographic variables. Few significant associations were revealed. Based on FDI and WHO estimates, the calculated periodontal treatment needs for the hospital employees was found to be about 2 hours per person. Compared with data for other countries, as reported by the WHO, this status demands serious efforts to be made towards periodontal health promotion. PMID- 1624205 TI - Disparity between medical and dental care of institutionalised elderly in Singapore. AB - Elderly persons tend to give dental care a lower priority than medical care. This study examined existing arrangements for and financial support of dental and medical care to elderly persons living in 68 long-term care facilities in Singapore. The chief administrators of all the homes for the aged were interviewed regarding the provision of physical and financial access to dental and medical care for their residents. Information was verified with a random selection of their residents. Results showed that a significantly higher number of homes (93 per cent) assumed responsibility for the provision of medical care than for dental care (70.7 per cent). A significantly greater proportion of them offered in-house medical care (42.6 per cent) than in-house dental care (5.9 per cent). Financial support for payment of providers' fees, hospitalisation and the transportation costs of ambulatory visits for both medical and dental care was found to be similar but generally inadequate. Greater commitment towards improving physical and financial access to dental care for the institutionalised elderly is necessary. PMID- 1624206 TI - LSA: a new liver-specific antigen in the rat. I. Purification and characterization. AB - A liver-specific antigen (LSA) was purified to homogeneity from rat liver by conventional methods of protein chemistry. By consecutive 100,000 g centrifugation, ammonium sulfate precipitation, ion-exchange chromatography on DEAE-cellulose, gel filtration on Sephadex G-200, ion-exchange chromatography on CM-cellulose and affinity chromatography on concanavalin-Sepharose, it has been possible to isolate a preparation that migrated as a single band on SDS-PAGE. This preparation gave a complete identity pattern with the original crude rat liver extract when tested by double immunodiffusion. This antigen has a molecular weight of 72.5 kD with an electrophoretic mobility in the region of alpha 2 globulins. The LSA proved to be thermolabile since exposure to 55 degrees C completely destroyed the antigen. Exposure of the LSA to different pH ranging from 4 to 10 had no detrimental effect on its antigenic activity. The amino acid composition of the LSA revealed that the acidic amino acids out-number the basic amino acids, with glutamic acid being the most abundant of them. Failure of beta mercaptoethanol to split the LSA molecule suggests the absence of sulfhydryl groups related to its antigenic activity. Subcellular fractionation of rat liver revealed most of the antigenic activity in the 100,000 g supernate, i.e. the soluble cytoplasmic fraction of the liver (cytosol). By contrast, the LSA was absent from isolated Kupffer cells from rat liver. The absence of any carbohydrate or lipid from the purified preparation of this antigen, in conjunction with the destructive effects of trypsin suggest that the LSA is a protein or a moiety closely associated with proteins. PMID- 1624207 TI - Frequency analysis of allergen-reactive T-lymphocytes in individuals allergic against the house-dust mite Dermatophagoides pteronyssinus. AB - We have investigated the frequencies of Dermatophagoides pteronyssinus (Dpt) reactive circulating T cells in individuals allergic to this house dust mite and in asymptomatic controls. In allergic patients the median for frequencies of Dpt reactive T cells (80/10,000 T cells) was significantly higher (p = 0.0001) than that in the controls (19/10,000 T cells). Frequencies of spontaneously proliferating T cells were also determined. Here too, marked differences (p = 0.0001) were observed between the allergics (median = 32/10,000 T cells) and the non-allergics (median = 7.5/10,000 T cells). The allergen-reactive T cells tended to occur at a higher frequency with increasing serum level of Dpt-specific IgE. Thus the median value for Dpt-reactive T cells in patients showing RAST class greater than or equal to 4 (176.5/10,000 T cells) was higher than that shown by patients with RAST class 3 (62/10,000 T cells). Frequency estimations of allergen reactive T cells before, during and after the completion of hyposensitization therapy might help to clarify their possible role in the allergic symptoms. PMID- 1624208 TI - Regulation of intestinal immunoglobulin production in response to dietary ovalbumin. AB - The effects of oral administration of ovalbumin (OVA) on intestinal immunoglobulin production was examined. Balb/c mice, bred and reared on an OVA free diet, received either one dose or 14 consecutive daily intragastric doses of 25 mg OVA/dose. Single dose administration of OVA resulted in significant suppression of total immunoglobulins in the intestinal mucosa, particularly of the IgA isotype, although a very low titre anti-OVA IgG class antibody response was induced. After multiple peroral immunisations, there was more intestinal anti OVA antibody induction and less suppression of total immunoglobulins. However, all the anti-OVA antibody was of the IgG isotype. In vitro production of mucosal immunoglobulins was not significantly reduced over 5 days, compared with controls, in either single or multiple administration groups, suggestive of a loss of T suppressor cell function in culture. Prior adoptive transfer of splenic and lymph node cells from mice preimmunised with OVA was capable of abrogating the local suppression of immunoglobulin production in vivo. Although adoptive transfer of bovine serum albumin-sensitised cells could also overcome some of the local suppression, complete restoration of normal immunoglobulin levels was not achieved. These data suggest that single oral administration of a novel dietary antigen induces a transient, non-specific suppression of intestinal immunoglobulin production, which can be overcome by antigen-specific T cells. PMID- 1624209 TI - Bronchoconstriction in helminthic infection. AB - In order to determine whether infection by helminthic parasites can be associated with a state of bronchoconstriction, we evaluated the response to the inhalation of a bronchodilator before and after long-term anthelmintic treatment of children in a urban slum of Caracas, Venezuela. In untreated children, a direct association was found between the degree of helminthic infection and the increase in peak expiratory flow rates caused by the bronchodilator. The elimination of the infections was accompanied by a significant decrease in response to the bronchodilator. These results indicate that helminthic infection could contribute to the development of asthmatic conditions in areas where these parasites are endemic. PMID- 1624210 TI - Grass aeropollen of the western United States Gulf Coast. AB - Volumetric air sampling was performed at Corpus Christi, Tex., September 1987 to August 1989. Grass aeropollen during all of 1988 accounted for 15.3% of total pollen captured during two major peaks, one in May and another during September and October. The remaining grass pollen, about one-quarter of the total, was found throughout the year with low levels in the winter and mid-summer. This bimodal pollen release corresponds to the flowering of two major types of grasses occurring in the western Gulf Coast region, the cool temperate species which are predominantly spring flowering in response to long-day photoperiodicity, and the more common warm temperate and subtropical species flowering by and large in the fall as short-day plants. Supplementing the already rich grass flora and adding to the high proportion of total aeropollen was the long distance dispersal of grass pollen found perhaps in sufficiently high quantities to trigger allergic symptoms and to cause grass pollinosis out of season, at least in acutely sensitive individuals. This occurred in late March, well before the spring peak in May. Correlations existed between near-drought conditions and reduced pollen shed in 1988, and normal precipitation and much higher pollen shed during parts of 1987 and 1989, illustrating the importance of environmental factors such as moisture on annual pollen frequency and level of pollinosis which can be variable and annually unpredictable. What is predictable is the genetically controlled timing of pollen maturation and release which will be generally the same year by year.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1624211 TI - Complete clarification of a case of farmer's lung. AB - The diagnostic curriculum to clarify a case of farmer's lung in a fibrotic stage is presented, including clinical functional tests, X-ray, analysis of cellular elements recovered from bronchioalveolar lavage, determination of precipitating antibodies in the circulation, histological and immunohistological studies of transbronchial lung biopsies. The patient had precipitating antibodies against several species of hay molds, especially Micropolyspora faeni, and immune complex deposition in the lung. Elution experiments on frozen sections of the lung biopsies and subsequent administration of patient's serum- or mold antigen specific antibodies combined with appropriate serum absorption experiments allowed the identification of the relevant antigen, i.e. M. faeni, in the deposited immune complexes. The immunohistological analysis of extracellular matrix components revealed an interstitial increase in procollagen and collagen type I and an even more pronounced augmentation of procollagen type III and fibronectin, i.e. a constellation characteristic for a chronic, active lung fibrosis that developed on the basis of an immune complex disease. PMID- 1624212 TI - The T-lymphocyte is the primary cellular target for potentiation of the in vitro T-dependent IgM antibody response by the B subunit of cholera toxin. AB - The B (or binding) subunit of cholera toxin (CTB) was reported previously to potentiate the in vitro T-dependent IgM antibody response by a mechanism independent of the cyclic AMP-generating capacity of the intact toxin. In the present report, experiments were designed to determine the immune cell type mediating potentiation by CTB. Firstly, CTB did not potentiate T-independent antibody responses at concentrations that effectively enhanced T-dependent responses. Secondly, separation/reconstitution studies with splenocytes from CTB- and vehicle-treated mice demonstrated potentiation of T-dependent responses by CTB treatment of either the Sephadex G10 non-adherent population or the T lymphocyte + macrophage population of cells. Potentiation was not observed by CTB treatment of the plastic adherent population or the B-lymphocyte + macrophage population. The evidence indicates that the T-lymphocyte is the primary cellular target for CTB-induced effects on the T-dependent IgM antibody response. Monosialoganglioside GM1, the putative binding site for CTB, is most likely the site of action for CTB on T-lymphocytes. These studies provide new insight on the mechanism of immunomodulation by cholera toxin, and CTB should provide a useful tool for further understanding the role of gangliosides in cellular immune responses. PMID- 1624213 TI - Modulation of tumor necrosis factor release from alveolar macrophages treated with pentamidine isethionate. AB - Alveolar macrophages in AIDS patients have a marked increase in tumor necrosis factor release in active Pneumocystis carinii pneumonia. We have demonstrated that pentamidine, an aromatic diamidine currently used to treat AIDS-related P. carinii pneumonia, is an effective inhibitor of cellular tumor necrosis factor release from lipopolysaccharide-stimulated rat alveolar macrophages at concentrations greater than 10(-8) M. Inhibition of release is not dependent upon the continued presence of pentamidine in the culture medium during the release phase. In addition, this blockage occurs at neither the transcriptional level as determined by Northern blot analysis nor the translational level as determined by Western blot analysis. Timed addition studies suggest that pentamidine is targeting relatively early events following lipopolysaccharide administration. Pentamidine appears to alter early lipopolysaccharide-induced cellular processes associated with the release of tumor necrosis factor from macrophages. PMID- 1624214 TI - Molecular requirements of endotoxin (ET) actions: changes in the immune adjuvant, TNF liberating and toxic properties of endotoxin during alkaline hydrolysis. AB - The effect of alkaline pH and alkaline hydrolysis on the physico-chemical and biological properties of endotoxin (ET) isolated from Serratia marcescens ATCC 13477 by the Biovin procedure was studied. Major emphasis was put on the ion exchange column chromatography and immune adjuvant activity (ADA) of the alkali treated samples. To measure changes in some endotoxicity parameters, Limulus lysate clotting (LAL), chick embryo lethality, Shwartzman skin reactivity and in vitro TNF release were measured. The toxic properties of ET, with the unique exception of the Shwartzman skin reactivity, rapidly diminished during alkaline treatment. As immunogen CBre3, a recombinant HIV glycoprotein which spans the C terminus of gp 120 and the N terminus of gp 41, was used in CD-1 mice, alkali treated and immediately neutralized ET samples (zero time) were inactive as adjuvants, in some cases immunosuppression could be clearly seen. But if the alkaline hydrolysis was continued for 6 h, the ADA became higher than it had been for the starting ET sample. Further alkaline hydrolysis eliminated the ADA of the samples. Both NaOH and propylamine acted similarly on the ET preparation. Reaction kinetic studies of the NaOH detoxification indicated the cleavage of ester bound acyl groups with low binding energy. Chemical analyses of the samples revealed that changes occurred in the fatty acid composition, characterized by a loss of approximately half of the 3-OH myristic acid content. PMID- 1624215 TI - Adjuvant activity of all-trans-retinoic acid in C57Bl/6 mice. AB - The effects of all-trans-retinoic acid were investigated on the immune responses in C57Bl/6 mice after daily oral administration for one week. In selected experiments the immunosuppressive chemicals, cyclophosphamide and cyclosporin A were used in conjunction with retinoic acid. Retinoic acid stimulated the production of antibodies against sheep red blood cells and DNP-Ficoll; however, retinoic acid did not reverse the depression caused by immunosuppressive chemicals. In non-immunized animals retinoic acid stimulated the production of IL 1 but not of IL-2. The mitogenic responses of splenocytes against concanavalin A, phytohemagglutinin and pokeweed mitogen were depressed after the retinoic acid treatment; those against lipopolysaccharide were not influenced. Treatment with retinoic acid did not alter the mixed leukocyte responses but increased the activity of NK cells. Results indicate that retinoic acid may act as an adjuvant via activating macrophages, however, retinoic acid cannot reverse the immunosuppression induced by potent chemicals. PMID- 1624216 TI - Detection of circulating anodic antigen before and after specific chemotherapy in experimental murine Schistosomiasis mansoni. AB - In two groups of mice infected with 60 (group I) and 120 (group II) Schistosoma mansoni cercariae, respectively, the effects of intensity and duration of infection, and of praziquantel therapy (curative vs subcurative dose) on the levels of circulating anodic antigen (CAA), were studied. CAA was measured in trichloracetic acid-treated serum samples with an avidin-biotin enzyme-linked immunosorbent assay (AB-ELISA) using the monoclonal anti-CAA antibody. Total worm burdens, oogram patterns and ova counts/g liver and intestine were followed up. The lowest detectable level of CAA was about 1.0 ng/ml, and was positive with a worm load of 3-5/mouse. CAA levels became already detectable as early as 1-2 weeks post-infection (pi) before any parasitological parameter and showed a significant drop from the 11th-12th week pi onwards. A positive correlation was demonstrated between the CAA level and worm load. Following successful praziquantel therapy, CAA disappeared earlier than any of the other parameters studied. PMID- 1624217 TI - Muramyl dipeptide-induced changes in murine splenocyte responses to concanavalin A. AB - The effect of muramyl dipeptide (MDP) on Con A-stimulated activation of murine spleen cells was studied. MDP was found to enhance or suppress the proliferative response of splenocytes when different concentrations of Con A were used. MDP was shown to change the IL-2 content in culture supernatants of stimulated cells and to influence IL-2-dependent proliferation of Con A-blasts. A high degree of correlation was found between the proliferation of Con A-blasts and the expression of IL-2 receptors on Con A-blasts. This correlation, however, disappeared in the presence of MDP. The effects of MDP were shown to depend on the level of initial cell activity or rather on conditions leading to a given initial activity of cells. PMID- 1624218 TI - Dose-related effects of oestradiol on rat thymic and splenic T-lymphocyte responsiveness to mitogens. AB - The dose-related effects of oestradiol on responses of thymic and splenic lymphocytes to mitogenic stimulation were studied in immature female Wistar rats. An attempt was made to relate responses not merely to dose but also to the circulating levels of the steroid. Lymphocytes were prepared from thymus and spleen and stimulated with phytohaemagglutinin (PHA) and concanavalin A (Con A) prior to measurement of 3H-thymidine incorporation. Oestradiol suppressed lymphoid tissue weight and cell number in a dose-related manner, but it was found, unexpectedly, that the dose of oestradiol used actually stimulated responsiveness of lymphocytes to mitogenic stimulation. Log dose-response curves indicate that the effects of oestradiol on responsiveness are complex, and the results suggest that the atrophic effects of oestradiol on lymphoid tissue and its enhancement of response to mitogens might be mediated by different mechanisms. Since the stimulant effects of the steroid were observed with serum levels of oestradiol attained both physiologically and pharmacologically, the results suggest a possible mechanism of action of oestradiol in abnormal cell proliferation, as occurs in neoplastic tissues, and might also help to explain certain sex-linked immune-related disorders. PMID- 1624219 TI - Potentiation of IL-2-induced t-cell proliferation by retinoids. AB - We evaluated the capacity of retinoids to potentiate proliferative responses of murine T-cells to recombinant human interleukin 2 (rIL-2). Concanavalin A (Con A) prestimulated spleen cells responded in a dose-dependent manner to added rIL-2. All-trans-retinoic acid (RA) at 10(-8) M potentiated the proliferative response by fivefold at saturating levels of IL-2. In similar experiments, two closely related retinamides, all-trans-(phenyl)retinamide (PR) and N-(4 hydroxyphenyl)retinamide (4-HPR), also potentiated murine splenocyte rIL-2 responses. Potentiation of IL-2-induced proliferation was dose-responsive to the concentration of added retinoid with peak potentiation occurring at 10(-10) - 10( 8) M in the presence of 10 U/ml rIL-2. Significant potentiation was observed at retinoid concentrations as low as 10(-14) M. Fluorescence flow cytometry of the responding cells revealed that among L3T4+, Lyt-2+ or total T-cells, at 72 h following Con A stimulation, essentially all of the cells expressed IL-2 receptors (IL-2R). This apparently represents near maximum IL-2R expression and treatment of the cells with retinoids did not increase IL-2R expression at that time point. The potentiation of IL-2 responses by retinoids was also observed with IL-2-dependent HT-2 cells, 98% of which were IL-2R positive. HT-2 proliferative responses to rIL-2 were potentiated as much as fourfold by 10(-10) M RA. HT-2 proliferative responses to rIL-2 were potentiated by all three retinoids dose dependently. Significant potentiation was observed with as little as 10(-14) M retinoid. Retinoids in the absence of IL-2 induced no proliferative responses. These data suggest that retinoids can augment the capacity of IL-2 to induce T-cell proliferation using Con A-activated murine splenic T-cell blasts and a long-term-cultured T-cell line. PMID- 1624220 TI - Oral administration of a streptococcal agent OK-432 activates alveolar macrophages in mice. AB - The effect of orally administered OK-432, a streptococcal preparation, on the functions of alveolar macrophages in mice was examined. The oral administration of OK-432 (1, 2 or 4 KE, four times every 3 days) augmented phagocytic activity, lysosomal enzyme activity and interleukin 1 (IL-1) production of murine alveolar macrophages recovered 5 days after the final administration while it did not augment H2O2 production. The number of alveolar macrophages was not affected by the same treatment. These results suggested that oral administration of OK-432 activates alveolar macrophages qualitatively to protect the lung from the metastasis of cancer cells and infectious diseases by pathogenic micro-organisms. PMID- 1624221 TI - Age-related influence of piracetam on mitotic index and number of silver-stained nucleolus organizer regions. AB - Mitotic indices and the number of silver-positive nucleolus organizer regions (AgNORs) were scored in phytohemagglutinin-stimulated cultures of peripheral lymphocytes from two age groups of females (mean = 23.1 and 84.0 yr, respectively) under the influence of Piracetam (2-oxo-pyrrolidine-1-acetamid; Nootropil, Reg. No. 17051) and in simultaneously set up control cultures without Piracetam addition. Piracetam concentrations of 10, 14 and 16 mg/ml culture medium produced a highly significant, decreasing effect on both parameters tested, without an age-related difference. Lower Piracetam concentrations (2 and 4 mg/ml culture medium) showed a depressant effect on some of the cultures only; but, on average, there was a rather equal, significant, dose-dependent, linear decrease of the mitotic indices of both age groups, whereas the suppressive effect on the number of AgNORs was significant in cultures from the young females only. PMID- 1624222 TI - Biological activity of chemically synthesized core sugar linked lipid A analog, heptose-(alpha 1----5)-2-keto-3-deoxyoctonic acid-(alpha 2----6)-2,3 diacyloxyacylglucosamine-4-phosphate. AB - The mitogenicity, lethal toxicity and antitumor activity against Meth A fibrosarcoma and the induction of tumor necrosis factor (TNF) of chemically synthesized compounds designated as A-103, 2,3-diacyloxyacylglucosamine-4 phosphate (GlcN-4-P), and A-503), heptose-(alpha 1----5)-2-keto-3-deoxyoctonic acid (KDO)-linked GlcN-4-P (A-103), were determined. Compound A-103 induced significant incorporation of [3H]thymidine of C57BL/6 mice at 25-100 micrograms/ml, and A-503 showed the highest incorporation of [3H]thymidine at 100 micrograms/ml. The mitogenicity of A-503 exhibited a lower activity than of A 103. Compound A-503 showed no lethality at high doses of 25 and 50 micrograms/mouse in C57BL/6 mice loaded with D-galactosamine, whereas A-103 caused the death of one of three mice at a dose of 50 micrograms/mouse. Although, the two compounds with or without muramyl dipeptide showed weak antitumor activity against Meth A fibrosarcoma in BALB/c mice, but there were no remarkable differences between the compounds on antitumor activity. Peritoneal macrophages, stimulated with A-103 or A-503 caused no production of TNF which induces L929 cell lysis in vitro. These findings indicate that the addition of heptose and KDO to GlcN-4-P seems not to affect mitogenic activity, lethal toxicity, antitumor activity and TNF-production of the GlcN-4-P compound (A-103). PMID- 1624223 TI - Mechanism of immunosuppressive effect of alprazolam: alprazolam suppresses T-cell proliferation by selectively inhibiting the production of IL2 but not acquisition of IL2 receptor. AB - The purpose of this study was to elucidate the mechanism of action of alprazolam on concanavalin A (Con A)-induced murine T-cell proliferation. Splenic cells of BALB/c mice were first cultured with an optimum dose of Con A in the presence or absence of varying doses of alprazolam to assess effects of alprazolam on T-cell proliferation, interleukin 2 (IL2) production and IL2 receptor (IL2R) expression. Then, Con A-induced T-blast cells from BALB/c mice were cultured with an excess dose of human recombinant IL2 (rIL2) or crude rat IL2 supernate in the presence or absence of alprazolam to assess the effects of alprazolam on the interaction of IL2 and IL2R. The results of these studies clearly demonstrated that alprazolam can inhibit the T-cell proliferation in response to Con A but not to IL2. Alprazolam also reduced the production of IL2 by splenic T-cells, but did not alter the expression of IL2R on Con A-induced T-blast cells. Furthermore, the results also showed that (a) alprazolam did not inhibit the proliferative response of splenic T-cells to a combination of phorbol 12-myristate-13-acetate (PMA) and ionomycin, and (b) the addition of exogenous IL2 reversed the inhibitory effect of alprazolam on T-cell proliferation. Finally, the addition of alprazolam produced a time-dependent inhibiting effect on T-cell proliferation. However, this inhibitory effect of alprazolam was abolished when the drug was added to the cultures of competent cells that fully expressed IL2R. Taken together, these results suggest that alprazolam inhibits murine T-cell proliferation by affecting the mitogenic receptor-mediated events (initiation) rather than the IL2R-mediated events (progression) of ligand-activated T-cells through the cell cycle. PMID- 1624224 TI - The unique interaction with immunity of FCE 24517, an antitumor drug with a novel mode of action. AB - The present study was designed to characterize in mice the effects on the immune system of the antineoplastic agent FCE 24517, a benzoic acid mustard derivative of distamycin A with specificity for AT-rich base pair sequences of beta-DNA. At antitumorally therapeutic doses, single injections of FCE 24517 caused profound leukopenia and a decrease of spleen cell numbers. However, primary and secondary antibody production to the T-dependent antigen sheep red blood cells were markedly increased by FCE 24517 given before or together with antigen. Antibody production to the T-independent antigen type III pneumococcal polysaccharide was not appreciably affected by FCE 24517. The delayed type hypersensitivity response to sheep erythrocytes was only marginally decreased, whereas proliferation of spleen cells to mitogens was markedly depressed. The ability of natural killer cells and macrophages to mediate cytotoxicity was not affected by FCE 24517 treatment. The ability of carrier-primed cells from drug-treated mice to cooperate for anti-trinitrophenyl antibody production increased twofold over that of vehicle-injected controls, suggesting an increase in T-helper cell activity. Serum cytokine levels were studied in mice injected with bacterial lipopolysaccharide used as a model stimulus. Peak levels of TNF and IL-6 were not modified by FCE 24517, but at later times higher amounts of cytokines were found in drug-treated mice compared with the control, suggesting a longer exposure of immunocompetent cells to these factors. Two compounds (FCE 24561 and CC-1065), also capable of binding AT-rich sequences in the minor groove of beta-DNA and containing an alkylating moiety, had immunomodulatory activity similar to FCE 24517 in increasing primary anti-sheep erythrocytes response. It is concluded that FCE 24517 exhibits a unique interaction with the immune system, markedly different from that of alkylating agents and may be representative of a novel group of antiproliferative-immunomodulating agents. PMID- 1624225 TI - Testosterone inhibits the immunostimulant effect of thymosin fraction 5 on secondary immune response in mice. AB - The purpose of the present investigation was to examine the in vivo influence of testosterone on the immune properties of a thymic factor (thymosin fraction 5, TF5) a partially purified thymic preparation in male Swiss IOPS/OF1 mice (5-10 weeks old). Testosterone administration (100 micrograms/ml) significantly inhibited the enhanced anti-sheep red blood cell antibody response induced by TF5 (100 micrograms/ml); this inhibition was only observed on the secondary antibody response and not on the primary. These results suggest that gonadal steroids can affect the immune response by modulating the activity of thymic factors. PMID- 1624226 TI - Anti-leprosy drugs inhibit the complement-mediated solubilization of pre-formed immune complexes in vitro. AB - Incubation of pre-formed immune complexes (IC) (125I-HSA--anti-HSA) with normal human serum resulted in solubilization of IC. When various anti-leprosy drugs were added to human sera, solubilization of IC was fairly explicit with clofazimine, whereas this effect was marginal with dapsone. Rifampicin hardly displayed this effect. Aspirin, chloroquine, and prednisolone, the drugs used in addition to multi-drug therapy to control reactions in leprosy, were in a position to inhibit the solubilization of 125I HSA--anti-HSA by normal serum only at a very high dose. From the current data of the inhibition of solubilization of pre-formed IC along with our earlier observations on the modulation of complement mediated haemolysis by these drugs, it may be possible to postulate that clofazimine as well as chloroquine affect early complement components. This may in turn be responsible for preventing the deposition of C3 complement onto IC. PMID- 1624227 TI - The toxicity of chemically deglycosylated ricin A-chain in mice. AB - Tumor-reactive antibodies coupled to ricin or its A-chain (immunotoxins) have been used in rodents and humans to treat a variety of neoplastic diseases. Side effects of such treatment include hepatotoxicity, vascular leak syndrome, myalgia and low grade fever. At high doses, severe toxicities include liver damage, pulmonary edema, aphasia, rhabdomyolysis and kidney failure. There have been a limited number of toxicologic studies on uncoupled ricin or its A-chain and none on deglycosylated A-chain. Since the latter has been utilized in "second generation" immunotoxins, the current studies were carried out to evaluate the toxicities induced by deglycosylated ricin A-chain (dgA) in mice. The administration of dgA to normal BALB/c mice causes early (24 h) weight loss and late (10 day) accumulation of ascites. These effects could be partially altered by changing the route of injection of dgA from i.v. to i.p. Thus, i.p. administration caused weight loss but not ascites, whereas i.v. administration caused both. Weight loss was associated with reduced fluid intake by the treated mice, and was not associated with increased levels of serum TNF-alpha. SCID mice injected with the same dose of dgA as normal BALB/c mice developed ascites, but it was of lesser severity, suggesting that a functional immune system, differences in microbial flora, or strain differences may be involved in the development of ascites. PMID- 1624228 TI - Studies on the immunological effects of fatty alcohols--I. Effects of n hexacosanol on murine macrophages in culture. AB - n-Hexacosanol (hexa), a long chain fatty alcohol extracted from Hygrophila erecta, has proved to possess neurotrophic activities on cultured neurons, and to attenuate the degeneration of cholinergic neurons after injury. In the present study, we show that hexa has also interesting properties on macrophages, a cell type largely represented in the brain: when added to mice resident peritoneal macrophages, it provokes significant morphological changes, and increases their phagocytosis capacity. These results may indicate that some membrane properties involved in these different effects and in macrophage functions are affected by n hexacosanol, but other sites of action could also be considered. PMID- 1624229 TI - Prenatal exposure to alcohol enhances thymocyte mitogenic responses postnatally. AB - Previous studies have shown altered cell-mediated immune responses in animals prenatally exposed to ethanol. The present study was designed to determine the ontogeny of proliferative responses of thymocytes postnatally following prenatal exposure to ethanol. Thymocytes obtained from 44-day old Sprague-Dawley male rats exposed to 5% (w/v) ethanol during the last two weeks of gestation had a significantly greater response to mitogenic stimulation by concanavalin A (Con A, 5.0 micrograms/ml) than controls. A similar trend was observed in rats at postnatal days 30 and 72, but not at day 16. Con A-conditioned thymoblasts from day-44 fetal alcohol-exposed animals were less responsive to further activation by a crude Con A supernatant than controls, but this response normalized by day 72. These findings reveal that the effects of ethanol exposure in utero in male rats include alterations in the development of thymoproliferative responses to mitogen which persist through the peripubertal period and normalize in part by young adulthood. PMID- 1624230 TI - [Multiple codification of the causes of death: from dying "of" to dying "from"]. AB - Multiple-cause mortality data is examined in the Valencian Region. In addition to coding the underlying cause of death (UCD), all causes of death which appeared mentioned on death certificates (MCD) were coded according to preliminary rules established by the Mortality Statistics Office. Specific diseases were selected to explore mortality patterns. The average number of conditions coded per death certificate was 2.7. Two or more conditions on the lowest used line appeared in 33.8% of all medical certificates. Septicaemia, high blood pressure and arteriosclerosis stand out among the conditions more often coded as MCD than coded as UCD. Exploring for mortality patterns a statistical association between coronary heart disease and diabetes emerged (p less than 0.0001). Multiple-cause mortality coding allow to discriminate mortality patterns and show a new magnitude to some specific causes of death. PMID- 1624231 TI - [Smoking habits in nursing students: prevalence, attitudes and knowledge]. AB - The purpose of this study has been to evaluate the prevalence of smoking habit, knowledge on the adverse health effects and attitudes towards it among nurses students in their three years of study (University School of Girona). A self administrated questionnaire was used. A total of 135 questionnaires were answered (88%) from an estimated available population of 154 students (94% females with 21 years old of mean age). The prevalence of current smoking was 34.3%; ex smokers 23.3% and non smokers 42.5%. The mean of tobacco consumption was 367.6 cigarettes/month. 92% no smokers, 91% ex smokers and 76% smokers thought that smoking has adverse health effects (p less than 0.001). They consider the health protection like the first reason to give up smoking. 38% will advise their healthy smokers patients about the risk of their habit. We conclude: 1.-Low prevalence of smoking habit; 2.-Nurses should know methods aimed at lowering smoking rates, assuming that they have determined influence on the population behavior. PMID- 1624232 TI - [Hospital utilization and increasing old age in the user of care?]. AB - Data are presented on hospital stay for the population 65 years-old and over, measured in percentage over the total for Spain, for the 1978 to 1988 period, by gender, for each province and autonomous region (Comunidad Autonoma). The country's total for the last available year was 35%. Except in Baleares and Murcia, the proportion of hospital stays increased in all Regions, especially in Navarra, where it increased from 23% to 51%. After adjusting for age, the increase in the proportion of hospital stays in the study population was due to an increase in utilization per person. The proportion, which was 13.3% in 1978, raised to 23.8% in 1988, with an adjusted value of 21.3%. PMID- 1624233 TI - [Primary-care morbidity and true morbidity due to acute respiratory infections]. AB - The present work presents the study of morbidity due to acute respiratory infections (ARI) in areas of the town of Lisa in Ciudad Habana, and Isla Juventud (Cuba), to characterize different aspects of morbidity measured by health care attendance and to measure true morbidity. About 90% of consultations for ARI were first-time consultations, while their ratio to further consultations was 5.3. True morbidity rates (TMR), obtained trough active research, ranged from 110.4 to 163.4 cases per 1000 inhabitants, considerably higher than morbidity rates measured by primary care consultations (MRPCC) in the same time period. The true morbidity index (TMI), as measured by the ratio of the two previous rates, ranged from 5 to 15. A high proportion (47.6%) of cases reported no medical care attendance. These results provide approximate estimates of true morbidity in the study area, and allow the establishment of a new control program, also improving epidemiologic surveillance within primary care activities. PMID- 1624234 TI - [Strategies in measuring nursing care]. AB - When resources are limited, the balance between the supply and the demand of nursing care is becoming more and more necessary. This situation justifies the use of tools to measure work charges in nursing. This article analyses the relationship between work charges and time estimation in nursing care. From a bibliographical review on this topic it discusses possibilities and techniques of time estimation for the nursing care given to a patient, as well as the caring time he or she requires. Two different approaches and some conclusions from the analysis of both of them are showed: first; the direct method, i.e. that of measuring caring levels; and secondly, the indirect method, that is a system for classifying patients. The interest of the direct method is advocated because of its clarity, external validation possible integration in nursing care plans. PMID- 1624235 TI - [An analysis of survival data in the epidemiological context]. AB - The present work reviews the methodology of survival analysis in the epidemiological field, especially within the framework of cancer registries. The main concepts used in survival analysis are presented, and the problems of competing mortality, as well as variable and stage adjustment are also discussed. Although the estimation and comparison of survival data distributions obtained from epidemiologic observations is technically possible nowadays thanks to a variety of statistical methods which take into account multiple proGnostic factors, it is proposed that pilot studies should be undertaken to look at the main problems related with potential selection biases and the standardization of prognostic factors to be evaluated. PMID- 1624236 TI - [A consensus on consensus conferences]. PMID- 1624237 TI - An unusual complication of extracorporeal shock wave lithotripsy: urinoma due to rupture of the renal pelvis. AB - A case of a female patient with urinoma due to rupture of the renal pelvis after extracorporeal shock wave lithotripsy is described. Although temporary perirenal fluid accumulations after extracorporeal shock wave lithotripsy have been reported previously, possibly this is the first case presenting with an abdominal mass due to retroperitoneal urine collection. PMID- 1624238 TI - In situ extracorporeal shock wave lithotripsy for upper ureteral stones: experience with 65 patients. AB - A total of 65 patients with 67 upper ureteral stones underwent in situ extracorporeal shock wave lithotripsy (ESWL) between March 1990 and September 1990. For stone disintegration the electrohydraulic shock wave lithotripter Tripter XI (Direx) was used. Eighty-seven per cent of stones showed satisfactory disintegration after the first treatment and a further 9 per cent after repeat treatments. The stone-free rate at 12 weeks was 85 per cent. General anaesthesia was needed in only 12 per cent of patients. The retreatment rate was 13 per cent. It was concluded that in situ ESWL is an effective procedure with negligible morbidity for treating upper ureteral stones. PMID- 1624239 TI - Ureteral incarceration in the symptomatology of hydronephrosis. AB - Renal colic symptoms may be caused by an aberrant vascular bundle that intermittently incarcerates the pyeloureteral junction. The authors describe 6 patients who were complaint free except for the period of fits and routine urological examinations showed normal findings. The patients had no subjective complaints after open surgery. PMID- 1624240 TI - Ureteral fibroma: an unusual clinical symptomatology. AB - The authors describe a case of ureteral fibroma. The aetiology, clinical symptomatology and diagnosis are discussed, and differentiation between benign and malignant lesions is emphasized. PMID- 1624241 TI - Nitrofurantoin versus trimethoprim for low-dose long-term prophylaxis in patients with recurrent urinary tract infections. A prospective randomized study. AB - In a prospective randomized study 38 patients with recurrent urinary tract infections (rUTI) were included to take either 50 mg Nitrofurantoin (n = 19) or 50 mg Trimethoprim (n = 19) as low-dose long-term prophylaxis for half a year. Compliance was checked weekly by Bacillus subtilis spore test strips sent in by mail. The infection rate was reduced from more than three per patient year to 0.01. There were no significant differences between the two groups concerning the recurrence rate (Nitrofurantoin: one rUTI; Trimethoprim: three rUTI) or side effects. Under Nitrofurantoin treatment 3 symptomatic fungal infections occurred. Trimethoprim and Nitrofurantoin are equally suitable for low-dose long-term prophylaxis in rUTI. Surveillance of compliance gives important hints for failure of prophylaxis. PMID- 1624242 TI - Severe obstruction of the urinary tract due to talcum powder granuloma after surgery. A case report. AB - Talcum powder which is generally used for lubrication of surgical gloves can be responsible for granuloma formation with subsequent complications. This is the report of a case with progressive urinary tract obstruction. PMID- 1624243 TI - Cytologic findings of fine needle aspirates in chronic prostatitis. AB - Cytologic studies in patients with prostatic infection, primarily those with chronic prostatitis, were conducted on samples obtained by the fine needle aspiration method. Infiltration of inflammatory cells such as polymorphonuclear leukocytes and macrophages was observed to a greater extent in patients with chronic bacterial prostatitis as compared to those with chronic nonbacterial prostatitis or prostatodynia. The pathogen was isolated in only one out of 28 patients with chronic bacterial prostatitis. We concluded that fine needle biopsy is useful for assessing patients with prostatic inflammation, but not for detecting microorganisms because of focal colonization of the organisms in the glands. PMID- 1624244 TI - Uroflow via stenotic urethra. AB - A DANTEC 2100 mictometer type 21C10 with uroflow transducer type 21KO2 was used for investigation of 50 men with urethral strictures (mean age 59 +/- 14 years). The patients underwent a total of 334 clinical evaluations of replicate voiding (minimum 4, maximum 16) before and after successful urethral dilatation on an outpatient basis. Using t-paired comparison test, significant increase in maximum urinary flow rate (P less than 0.01) after the treatment procedure was evidenced in each of the patients. The variability of other urinary flow parameters suggested a lower significance in evaluation of urine stream quality. The McNemar test showed a significant shift from one to another zone of classification suggested by Drach et al. (P less than 0.01), i.e. 64% of patients reached normal or overlap zone in the first spontaneous voiding after urethral dilatation. Furthermore, no significant difference could be established with one-way ANOVA between urodynamic variables of mean values of repetitive voidings in cases of urethral stenosis of different aetiology either before or after urethral dilatation (P greater than 0.05), suggesting that urethral stenoses of different aetiology are characterized by similar urodynamic features. A highly significant linear correlation was found between the maximum flow rate and the voided volume only after urethral dilatation (r = 0.522, P less than 0.01), while correlation with urethral sound sizes could not be established (r = 0.207, P greater than 0.5). We conclude that uroflowmetry provides reliable information on the patient's ability to void. The use of maximum flow rate may predict the time at which urethral dilatation becomes necessary and provides objective evidence of the efficacy of treatment. PMID- 1624245 TI - Erectile dysfunction due to venous incompetence treated by dorsal vein ligation. AB - The authors describe 14 cases of erectile dysfunction. The sites of leakage were detected by duplex or colour flow Doppler sonography. Treatment by dorsal vein ligation resulted in fairly good early responses, however, at 4-month follow-up the great majority of patients returned to the original functional state. PMID- 1624246 TI - Pituitary and gonadal functions in patients with chordee without hypospadias. AB - Pituitary and gonadal functions in 16 prepubertal boys with chordee without hypospadias by stimulation of gonadotropin releasing hormone or human chorionic gonadotropin were compared to those of age-matched normal boys. The patients with chordee without hypospadias had poor follicular stimulating hormone response but pituitary luteinizing hormone reserve function was normal. Testosterone response by stimulation of human chorionic gonadotropin was not impaired in patients with chordee without hypospadias. The results suggested that chordee without hypospadias may also be categorized into hypospadias from the aspect of its pituitary and gonadal functions in addition to the embryogenesis of chordee. PMID- 1624247 TI - Two-stage surgical treatment for male transsexuals. AB - A plan for complex treatment of male-to-female transsexuals is presented. On the basis of our experience in the management of 15 patients, two-stage surgical treatment aiming at the change of external genitals, as well as the obtained cosmetic and functional results are described. PMID- 1624249 TI - Multiple bone fractures following an epileptic seizure in renal osteodystrophy. AB - Seizure induced bone fractures in patients with renal osteodystrophy are uncommon. A case is described where multiple bone fractures occurred following convulsions which appeared shortly after haemodialysis. PMID- 1624248 TI - Influence of antiplatelet drugs on occlusion of arteriovenous fistula in uraemic patients. AB - A long-standing arteriovenous (A-V) fistula may develop thrombotic complications. In 20 patients on intermittent peritoneal dialysis (IPD) arteriovenous fistula was made surgically. We evaluated the efficacy of three antiplatelet drugs: Ibustrin (Group A), sulphinpyrazone (Group B) and alpha-tocopherol (Group C) in preventing thrombotic occlusion of A-V fistulas. Results of the trial indicate that the three drugs significantly reduce spontaneous platelet aggregation and ADP induced aggregation. The heparin neutralizing activity was significantly increased during treatment. Significant prolongation of bleeding time was observed only in Groups B and C. In patients receiving antiplatelet drugs no occlusion of A-V fistulas was observed. In the control group such complications occurred in 3 of the 20 patients. Our results indicate that antiplatelet drugs by inhibiting the platelet function may prevent thrombotic occlusions of A-V fistulas in IPD patients. PMID- 1624250 TI - Deoxyribonuclease activity in T and B lymphocytes of haemodialysed patients with uraemia. AB - Deoxyribonuclease (DNase) activity and metal ion concentrations in lymphocytes of patients with chronic renal failure and in healthy controls were studied. The data suggest that T and B lymphocyte nuclei of patients with renal failure show increased DNase activity when compared to their healthy counterparts. It is suggested that the enhancement of enzyme activity is a result of increased metal ion concentration rather than increased enzyme copy count. The data strongly suggest that haemodialysis of uraemic patients is more effective for improvement of lymphocyte metabolism than the conservative chemical treatment. PMID- 1624251 TI - Endopyelotomy for ureteropelvic junction stenosis. AB - The authors review their experience with percutaneous endopyelotomy in the treatment of ureteropelvic junction (UPJ) stenosis. The method was used in 64 patients of whom 59 had also renal stones. There was only one patient with secondary UPJ stenosis following pyeloplasty. The total success rate was 61%. It is pointed out that the results depend in a great part on the skill of the surgeon. PMID- 1624252 TI - Calculous pyelonephritis. AB - The authors report on 48 patients with calculous pyelonephritis. Urinary obstruction was caused by renal calculi in 21 patients and ureteral calculi in 27. Urine cultures were positive in 87.5% and bacteremia was seen in 70%. The common organisms in urine and blood culture were E. coli, Proteus and Klebsiella. Septic shock occurred in 10 (20.8%) out of 48 patients. Calculous pyelonephritis with urinary obstruction is a very serious condition. PMID- 1624253 TI - Diclofenac sodium suppository in the treatment of primary nocturnal enuresis. AB - The prostaglandin synthesis inhibitor diclofenac sodium was given as suppository in the treatment of primary nocturnal enuresis in 24 patients. The statistically significant difference in response to diclofenac sodium and to placebo leads us to use diclofenac sodium in primary nocturnal enuresis. PMID- 1624254 TI - Urovaginal fistulas: experience with the management of 41 cases. AB - In a retrospective analysis the authors have evaluated their experience with the management of urovaginal fistulas in 41 patients. Of them 34 had vesicovaginal, 3 ureterovaginal, 2 urethrovaginal, 1 ureterovesicovaginal and 1 ileovasicorectovaginal fistula. Fistulas occurred most frequently after gynaecological operations for benign and malignant diseases and after radiotherapy. Reconstructive operations were performed in 37 patients, mostly from the vaginal approach. Primary repair of fistulas was successful in 35 patients. In 2 patients reoperation was required. Due to good experience the authors recommend the transvaginal approach, which in their opinion is suitable for repair of the prevailing part of vesicovaginal fistulas. PMID- 1624255 TI - The significance of serum lipid-bound sialic acid in bladder tumours. AB - Tumour markers with high sensitivity and specificity for bladder cancer are still lacking and several markers have been investigated up to now. Serum lipid-bound sialic acid (LSA) was claimed to be a tumour marker by some investigators and this study tried to assess the value of LSA as a tumour marker in patients with bladder cancer. The results obtained from 27 patients and 30 controls showed that serum LSA levels remained within the suggested normal limits of the method used but they were significantly higher than in the controls. The value of serum LSA is questionable as an initial tumour marker for bladder cancer, but variations from the basal level may indeed be helpful in monitoring the efficacy of the therapy and in detecting relapses during follow-ups. PMID- 1624256 TI - Long-term BCG immune therapy of superficial bladder tumours. AB - Long-term local BCG treatment of superficial bladder tumours is described and the 5-year results are reviewed. Complications of major significance in the course of immune therapy did not occur, loss due to death was not recorded. PPD skin test failed to furnish extra information regarding the biologic behaviour of the tumour. Annual repeats of the therapy promise better results than one single 6 week course. PMID- 1624257 TI - A simple modification using the appendix as efferent limb in ileocolonic reservoir (Mainz pouch). AB - The appendix was used as an efferent limb of the ileocolonic pouch (Mainz pouch) in two patients who underwent radical cystectomy for invasive bladder cancer. The pouch has a low pressure character and sufficient capacity as well as complete continence. This procedure is relatively simple to perform and considered to be a useful modification of ileocolonic pouch. PMID- 1624258 TI - In vitro study of rat prostate 5 alpha-reductase activity and its inhibition. AB - A simple and rapid method of measuring 5 alpha-reductase (5 alpha-R) activity and of determining the kinetic parameters (KM and Vmax) of the enzyme is described. The 5 alpha-R activity in the homogenate of the prostate of Wistar rats aged 8-12 weeks was established, and the effects of natural and synthetic steroids and of non-steroidal antiandrogens (IC50) upon the 5 alpha-R activity were studied. Of the natural steroids, 17-OH-progesterone was found to have the highest inhibitory effect (IC50 = 1.35 microM), followed in decreasing order by progesterone (IC50 = 5.0 microM) and 4-androstene-3,17-dione (IC50 = 21.6 microM). Oestradiol-17 beta had practically no inhibitory effect. Of the synthetic steroids, 4-MA had the highest inhibitory effect (IC50 = 0.068 microM), followed by nortestosterone (IC50 = 7.4 microM) and RU-486 (Mifepristone) (IC50 = 115 microM). Even at 1000 microM, cyproterone acetate exerted no inhibitory effect. Of the nonsteroidal compounds, ketoconazole proved a weak inhibitor (IC50 = 115 microM), while flutamide was practically ineffective. PMID- 1624259 TI - The cost and availability of therapeutic options in advanced prostatic carcinoma in Turkey. AB - Advanced prostatic carcinoma may be treated by a variety of methods of endocrine manipulation which affect the production of androgens. This can either be done by bilateral orchiectomy or by a number of drugs. Orchiectomy has two advantages: low cost and being a once-only procedure. This report outlines the costs of various methods of hormonal treatment and compares them with each other in Turkey. PMID- 1624260 TI - Genital infections in men associated with Chlamydia trachomatis. AB - The advent of new diagnostic procedures has made it possible for urologists to detect chlamydial presence in genital infections. Many studies have shown chlamydial association with urethritis. However, its presence in prostatitis and epididymitis has not been clearly defined yet. In this study we investigated the presence of Chlamydia trachomatis using enzyme linked immuno assay (ELISA) antigen and antibody detection method in sexually active men with different genital infections. We have found that in 32.1% of patients with non-gonococcal urethritis chlamydial antigen is detectable. We also have been able to detect chlamydial antigen in two patients with chronic non-bacterial prostatitis, but in no patients with epididymitis. We conclude that besides its presence in urethritis, there is an association between chlamydia and chronic prostatitis. Yet, further studies are needed to delineate this association more clearly. PMID- 1624261 TI - Long-term results of treatment of male urethral strictures using direct vision internal urethrotomy. AB - This study presents long-term results of treatment of urethral strictures in 178 men who underwent direct vision cold urethrotomy between January 1, 1979 and December 31, 1984. Satisfactory urodynamic results were achieved in 69.7% of cases. PMID- 1624262 TI - Definition and treatment of chordee without hypospadias: a report of 5 cases. AB - The controversies in chordee without hypospadias are mostly focussed on the definition and treatment of type I and type IV chordee. In this respect we believe that surgical exploration is necessary to make a precise classification leading to the most appropriate therapy. We present 5 cases, 3 of which had type I chordee, 1 had type II and 1 had type III. In the 2 cases with type I chordee, type IV chordee coexisted. Although all the patients have had satisfactory cosmetic results, 3 of them should be reevaluated after puberty since they are prepubertal yet. PMID- 1624263 TI - Different types of median raphe cysts in the penis. AB - We report a case of different types of median raphe cysts in the penis. The literature is reviewed and the origin of these cysts is discussed. PMID- 1624264 TI - Squamous cell carcinoma of the penis. Analysis of 24 cases. AB - The authors evaluated retrospectively 24 cases of spinocellular carcinoma of the penis, trying to detect aetiological carcinogenic factors of the disease. Phimosis persisting since childhood was reported by ten men, whereby in five of them circumcision was performed during puberty. The duration of symptoms up to the time of biopsy and histological verification of differentiated spinocellular carcinoma of the penis varied from one month to thirteen years. Eight patients (33.3%) belonged to category T1, 8 (33.3%) to T2 and 8 (33.3%) to T3. Fifteen tumours (62.5%) were G1, 5 (20.8%) G2 and 4 (16.7%) G3. In 5 men print cytology was negative. PMID- 1624265 TI - Diagnostic value of creatine phosphokinase in testicular torsion. AB - In an experimental study on 36 male guinea pigs testicular torsion was induced in 10, epididymitis in 10, surgical trauma in 6 and only ether anaesthesia was given to 10 animals. Serum creatine phosphokinase (CPK) levels at 0, 4, 8, 20, 28 and 40 hours were determined in each group. Serum CPK levels were found to rise significantly in the torsion group. Determination of serum CPK levels may be an auxiliary alternative in the diagnosis of testicular torsion. PMID- 1624266 TI - Liposarcoma of the perineum and scrotum. AB - A case of liposarcoma of the perineum and scrotum, which presented as a huge haematoma and was left in place for three years prior to excision, is presented. The patient was treated by wide excision of the tumour, orchiopexy to the inguinal region and radiotherapy. To date, 30 months following surgery, the patient is completely asymptomatic and no tumour recurrence is evident either on physical and rectal examinations or on chest X-rays, ultrasonography and abdominal and pelvic computerized tomography. PMID- 1624267 TI - [Introductory Press Conference: Toratex--the new mono-analgesics in acute, intense pain. Frankfurt, 21 February 1992]. PMID- 1624268 TI - Donaldson v. Van de Kamp. PMID- 1624269 TI - Ragona v. Preate. PMID- 1624270 TI - Beverly Hills Bar Association report to the House of Delegates. PMID- 1624271 TI - American Bar Association. Commission on Legal Problems of the Elderly. PMID- 1624272 TI - Reimbursement rates and quality of care in the dialysis industry: a policy discussion. PMID- 1624273 TI - 4th meeting of the Sardinian Group of the Italian Biochemical Society, Cagliari, June 13-14, 1991 and meeting on "Macromolecular Interactions" of the Lazio Abruzzi-Molise Group of the Italian Biochemical Society, Rome, June 14, 1991. Abstracts. PMID- 1624274 TI - Interaction of tonic labyrinth and neck reflexes in man. AB - Interaction of tonic labyrinth and neck reflexes was studied in 3 healthy volunteers by analyzing changes in Soleus H-Reflex (SHR) area in relation to both lateral tiltings and neck rotations. By using a Kermath chair each subject was tilted laterally from the vertical to the left and to the right up 15 degrees in steps of 5 degrees and at the same time the longitudinal body axis, keeping the head fixed, was rotated to the right and to the left up to 15 degrees in steps of 5 degrees. All combinations of lateral tiltings and neck rotations were tested. Each test position was followed by a return to 0 degree for both rotation and tilting (control position). Twelve H-reflexes of right soleus muscle were recorded in each test and control position and the changes in RSHR area were expressed as percentage variations from the mean value absorbed in the pretest and post-test control position. Our data indicate that in man, as in animals, labyrinth and neck reflexes act in the opposite direction, and that in the static condition their contribution to postural stabilization is equal. PMID- 1624275 TI - The tilting cardiovascular response in orthostatic syncope. AB - 159 patients with a previous discharge diagnosis of recurrent vasodepressor syncope associated with prolonged standing or other circumstance known to trigger the condition were examined in order to isolate the orthostatic form. 72 patients with a history of at least two episodes of loss of consciousness after standing still for at least 10' were selected for testing by head-up tilt. Those who showed signs or symptoms during the test were tested a further twice, the third time after atropine administration. This process resulted in the diagnosis of orthostatic vasodepressor syncope in 28 patients who presented both 1) a positive test associated with hypotension and bradycardia and 2) bradycardia-free hypotention on repetition of the test with atropine. PMID- 1624276 TI - Cerebrovascular disorders and alcohol intake: preliminary results of a case control study. AB - The role of alcohol as a risk factor for cerebral infarction and hemorrhage has been assesed in 200 middle-aged and elderly stroke patients and 200 controls matched for age, sex and hospital admission date. Computed tomographic brain scans were done in all but 10 of the stroke patients. Alcohol intake was reckoned on the 12 months preceding hospitalization and expressed in grams daily according to a standard nomogram. The Michigan Alcoholism Screening Test was used for the diagnosis of alcoholism. Cerebral infarction was present in 59% of the stroke patients and cerebral hemorrhage in 9%. The role of alcohol as risk factor for stroke proved to be small (Odds Ratio 1.86) and was practically lost after adjustment for the most common risk factors for cerebrovascular disorders (previous strokes, arterial hypertension, diabetes, obesity and hyperlipidemia). Our findings seem to suggest that alcohol is not an independent risk factor for stroke in the middle-aged and elderly. The data are, however, preliminary and are discussed in the light of methological problems. PMID- 1624277 TI - Prevalence of moderate and severe Alzheimer dementia and multi-infarct dementia in the population of southeastern Sicily. AB - We have calculate the prevalence rates of moderate and severe dementia of the Alzheimer type (DAT) and of multi-infarct dementia (MID) in a Sicilian population sample aged 40 and over. For DAT the prevalence rate is 0.80% among the over 40s and 2.42% among the over 65s. The prevalence rates for both types, but especially for DAT, increase higher prevalence of primary degenerative dementia among females. PMID- 1624278 TI - Localization of the pathological process in Miller Fisher syndrome. AB - A 64 year old woman died at the third attack of MFS. Histological examination demonstrated segmental demyelination and axonal swelling of the peripheral nerves studied, oculomotor included. In the C.N.S. only mild chromatolytic changes and rare pyknosis of the nerve cells in the midbrain were found without signs of primary inflammation. We reviewed the findings in all the 4 anatomoclinical cases of MFS and in 2 cases of GBS with ophthalmoplegia or ataxia. With one exception, they appear to be concordant with those of our case. As the histological examination showed CNS involvement consequent upon peripheral nerve impairment, we are bound to change our opinion on the nosological position of MFS. Any small CT enhancements in the brain in MFS may be due, as in some cases of demyelinating polyneuropathy, to focal rupture of the blood-brain barrier. PMID- 1624279 TI - Dexamethasone suppression test, melatonin and TRH-test in cluster headache. AB - The origin of Cluster Headache (CH) is still unknown. The periodicty and presence of symptoms due to both sympathetic and parasympathetic activity suggest the involvement of central nervous system structures, particularly the hypothalamus. To investigate hypothalamic involvement in CH, we employed a neuroendocrinological approach. We observed a normal dexamethasone suppression test (DST) in all patients, increased cortisol plasma levels in remission patients at 8.00am before and at the end of the DST, while only in CH patients during cluster period did we find a reduced TSH response to TRH and a reduced night-time melatonin peak. The neuroendocrinological derangements found in CH may be consistent with hypothalamic involvement. PMID- 1624280 TI - A case control study of CSF copper, iron and manganese in Parkinson disease. AB - To elicit possible variations in the CSF concentrations of copper, iron and manganese due to Parkinson disease (PD) or to the stage reached, we tested 11 patients with idiopathic PD, 6 untreated and 5 on long term L-dopa, versus 22 age and sex matched patients with other neurological disorders (control group-CG). The CSF levels of the three metals, measured by electrothermal atomization, did not differ significantly between the PD group and CG or between either of the PD subgroups and CG. Our findings therefore do not support the hypothesis that CSF Cu is a marker of PD. PMID- 1624281 TI - A case of diffuse lupus encephalopathy successfully treated with high-dose intravenous methylprednisolone. AB - We report a case of systemic lupus erythematosus (SLE) in a young woman who presented a serious encephalopathy with respiratory distress and coma, after arbitrary interruption of oral corticosteroid therapy when her first pregnancy ended in abortion. The patient showed rapid improvement on methylprednisolone pulse therapy. The case suggests the utility of such a therapy in severe, non focal, CNS complications of SLE. PMID- 1624282 TI - Calf hypertrophy due to a iatrogenic sciatic nerve lesion: case report. AB - We report a case of calf hypertrophy due to a iatrogenic sciatic nerve lesion. Nerve damage may cause hypertrophy rather than the atrophy usually seen. Ephaptic transmission among nerve fibers at the point of lesion may cause the hypertrophy. The inability of the hypertrophic muscle fibers to compensate for the atrophic fibers accounts for the muscle weakness. PMID- 1624283 TI - Alternating hemiplegia of childhood: case report. AB - We report the case of a 3 1/2 year old girl who had had attacks of alternating hemiplegia from the age of 6 months. Peculiar features from the etiopathogenetic angle seem to be the presence of a ring of mild stenosis of the vertebral artery on the right side, the influence of the upright posture on the onset of the attacks and perhaps also of variations in atmospheric pressure. The only drug that had some effect was flunarizine. Phenobartbital, haloperidol and nadolol had no appreciable effect. PMID- 1624284 TI - Giant congenital nevus and chronic progressive ascending hemiparesis (Mills syndrome). Report of a case. AB - We describe the case of a 20 year old boy with a giant congenital nevus who developed a chronic progressive ascending hemiparesis. The association of the pigmented lesion with a focal neurological deficit is pathognomonic for neurocutaneous melanosis complicated by a leptomeningeal melanoma. MR imaging at 1.5 tesla ruled out such a possibility and showed a small aspecific pontine lesion along the route of the corticospinal tract. We discuss possible etiologies. PMID- 1624285 TI - Reflex sympathetic dystrophy in a child. AB - We describe a 9 1/2 year old girl who suffered from severe recurrent pain and functional limitation in her right leg with hyperesthesia, hyperalgesia, color change and edema as the presenting symptoms, during the previous two months. All laboratory tests were found to be normal and diagnosis of reflex sympathetic dystrophy was made. PMID- 1624286 TI - Transient abnormalities on magnetic resonance imaging after partial status epilepticus. AB - We report two patients who developed focal abnormalities on MRI after partial status epilepticus. Maximum radiological modification occurred in the area of maximal epileptic discharge. Subsequent MRI failed to demonstrate persistent abnormalities. These transient abnormalities on MRI could be an expression of cerebral edema caused by focal epileptic status. PMID- 1624287 TI - Neuroborreliosis: a Sardinian case with cerebellar symptoms. AB - We report the case of a patient long resident in Sardinia in whom the clinical history, neurological symptoms, serological and neuroradiological investigations pointed to the diagnosis of neuroborreliosis. We emphasize the rarity of cerebellar involvement in this disease. PMID- 1624288 TI - Head and neck sarcoma: report of the Head and Neck Sarcoma Registry. Society of Head and Neck Surgeons Committee on Research. AB - A Head and Neck Sarcoma Registry was established by the Society of Head and Neck Surgeons to review treatment results of a rare tumor by surgeons with special interest in this anatomic site. Two hundred fourteen patients were analyzed. There were 194 adult tumors and 20 pediatric tumors. The major sites included parotid and neck, 20%; face and forehead, 18%; maxilla and palate, 13%; scalp, 12%; mandible, 11%; paranasal sinuses, 7%; larynx, 2%; and oral cavity, 5%. Eighty-four percent were resectable. The disease-free survival was 56%; overall survival was 70% at 5 years. Major determinants of survival were adequacy of resection (margins free of tumor) and tumor type. Survival differed according to tumor cell type (tumor grade was not available). Patients with chondrosarcoma and dermatofibrosarcoma had survival approaching 100%. Patients with malignant fibrous histiocytoma (MFH) and fibrosarcoma (FSA) had intermediate survival of 60% to 70%. The worst survival, less than 50% at 5 years, occurred in patients with osteosarcoma, angiosarcoma, and rhabdomyosarcoma in decreasing order. This suggests a rationale for identifying high-risk patients for prospective adjuvant protocols. This study emphasizes the value of recording uncommon tumors to provide relevant information for future study and possibly therapy. PMID- 1624289 TI - Effect of advanced age and medical disease on the outcome of microvascular reconstruction for head and neck defects. AB - During the 5-year period from July 1984 to 1988, 72 patients over the age of 50 underwent microvascular free tissue transfers for head and neck reconstruction. There were 22 patients aged 50-59 years, 31 patients aged 60-69 years, and 19 patients aged 70-79 years. Seventy of these procedures (97%) were done at the time of ablative surgery utilizing a two-team approach. There was 1 total flap loss for a flap viability rate of 99% (73/74). There were 46 complications in 40 patients: 21 surgical and 25 medical. Twelve of the surgical complications required reoperation for a major surgical complication rate of 16%. Major medical complications developed in 12 patients (16%). Medical complications more commonly were observed in patients aged 60-69 years who had significant preoperative comorbidity and were classified as ASA class 3 or greater. There were 5 postoperative deaths for a mortality rate of 7%. Advanced chronologic age does not compromise the technical success of microsurgical free tissue transfer in the elderly patient with head and neck cancer. The risk of medical complications is significant and is directly related to concurrent illness of the individual patient rather than to age alone. PMID- 1624290 TI - Serous otitis media and paranasopharyngeal extension of nasopharyngeal carcinoma. AB - Two hundred thirty-two patients with nasopharyngeal carcinoma were evaluated for serous otitis media (SOM) at diagnosis. The diagnosis of SOM required the detection of effusion behind the tympanic membrane in association of air-bone gap of 10 dB or more in pure tone audiogram. These patients were also evaluated by computed tomography for the degree of tumor extension. By stepwise logistic regression analysis, the degree of paranasopharyngeal extension of tumor, erosion of petrous temporal bone, and the obliteration of pharyngeal recess were significantly related to the development of SOM, but sex and age were not. The findings of computed tomography may influence the plan of management for SOM in patients with nasopharyngeal carcinoma at diagnosis. PMID- 1624291 TI - Sensitivity of biopsy using local anesthesia in detecting nasopharyngeal carcinoma. AB - Flexible and rigid endoscopes allow good visualization of the nasopharynx using local anesthesia, and permit biopsies to be taken under direct vision. Little information is available on the accuracy of biopsies taken using local anesthesia, and general anesthesia is usually recommended for evaluation and biopsy of the nasopharynx to avoid missing small or submucosal lesions. We report the results from 260 patients biopsied using local anesthesia (188) and general anesthesia (72). All biopsies were taken using large nasal biopsy forceps under direct vision. The sensitivity of this technique in diagnosing nasopharyngeal carcinoma was 95.1% using local anesthesia and 95.6% using general anesthesia. We suggest that general anesthesia is rarely necessary for definitive biopsy of the nasopharynx. In the majority of patients, an accurate diagnosis can be obtained using large biopsy forceps under direct vision using local anesthesia. PMID- 1624292 TI - Botulinum a toxin for spasmodic torticollis: multiple vs single injection points per muscle. AB - Eighty-six injections in 49 patients with adult onset spasmodic torticollis were evaluated for efficacy with respect to single point per muscle versus multiple point per muscle injection techniques. Parameters of the syndrome assessed were pain, posture deformity, range of cervical motion, disfigurement, cervical muscle hypertrophy, activity limitation, and degree of involuntary movement. The multiple point per muscle injection strategy appeared superior to the single injection per muscle technique with respect to pain (p less than 0.002, chi square), posture deformity (p less than 0.001), range of motion (p less than 0.001), and improvement in activity endurance (p less than 0.001). No significant differences were noted with respect to cervical muscle hypertrophy or degree of involuntary movements, although the injections were considered beneficial in both groups to these syndrome components. PMID- 1624293 TI - Muscle tumors in the parapharyngeal space. AB - Tumors arising in the parapharyngeal space are rare. Even more rare are those which originate from the pharyngeal and parapharyngeal musculature. Three examples of muscle tumors presenting as parapharyngeal masses are reported, ie, a rhabdomyoma, rhabdomyosarcoma, and a leiomyosarcoma, and the literature pertaining to these tumors is reviewed. To the best of our knowledge, this represents the first case of a parapharyngeal leiomyosarcoma reported in the literature. PMID- 1624294 TI - Bilateral tonsillar metastasis of gastric adenocarcinoma. AB - The occurrence of metastatic tumors in the tonsils, although rare, must be considered in the differential diagnosis of tonsillar lesions. In particular, the review of the literature reports only 7 cases of tonsillar metastasis of gastric carcinoma. The authors describe a case of adenocarcinoma involving bilaterally the palatine tonsils and the lingual tonsil, in a patient previously operated due to gastric adenocarcinoma. The clinical appearance of the lesion could be also consistent with lymphoproliferative or infectious diseases. The clinical and pathologic differential diagnosis of this peculiar case is discussed, together with a brief review of the literature. PMID- 1624296 TI - 37th Annual Meeting of the Health Physics Society. Columbus, Ohio, 21-25 June 1992. Abstracts. PMID- 1624295 TI - Gene amplification and overexpression of epidermal growth factor receptor in squamous cell carcinoma of the head and neck. AB - The degree of gene amplification for epidermal growth factor receptor (EGFR) and its expression levels were examined in 4 cases of tumor lesions and their cell lines of human squamous cell carcinoma (SCC) of the oral cavity. The amplification was detected in 1 case (ZA), but not significantly in 3 other cases (HOC605, HOC815, and HOC927) in which the amplification did not occur during the cell line establishment. In those 3 cases, levels of EGFR synthesis and human EGF (hEGF) binding capacity were varied: HOC605 and HOC815 had slightly increased levels of hEGF binding capacity and EGFR synthesis, respectively. While HOC927 had the lowest levels of both, the hEGF binding capacity was elevated in the tumor lesion when compared with the normal counterpart of the same patient. These results suggest that the increased capacity for EGF binding plays a more important role than does gene amplification on the tumorigenesis of SCC of the head and neck. PMID- 1624297 TI - Educationalists express their concerns. AB - The UKCC has received well over a thousand responses to their proposals for community education and practice (CEP). Here we reproduce an extract from the response of the United Kingdom Standing Conference on health visitor education (UKSC) by Frances Appleby and Joy Merrell, UKSC chair and honorary treasurer respectively. PMID- 1624298 TI - A route from two roots. PMID- 1624299 TI - Clues to the detection of fragile X syndrome. AB - Ioanna Giannopoulou and Jeremy Turk outline the clues to the detection of fragile X syndrome, the commonest cause of familial mental handicap. Health visitors have a crucial role in the early diagnosis of the syndrome. PMID- 1624301 TI - Supporting teenage mothers. PMID- 1624300 TI - Health visitors and child accident prevention. AB - Yvonne H Carter, Michael J Bannon and Peter W Jones explore the role of health visitors in child accident prevention in North Staffordshire, to assess their knowledge and awareness of local data and to facilitate more effective planning of educational provision for health visitors and other primary health care workers. PMID- 1624302 TI - Sickle cell disorders and the schoolchild. PMID- 1624303 TI - Cervical screening: default and compliance. AB - Health visitors could play a key role in educating at risk women about the benefits of cervical screening. Jane Martin and Peter J Main examine some of the models which outline barriers to screening uptake and consider which will help the health visitor to increase the knowledge and understanding of at risk clients. PMID- 1624304 TI - Cigarette butts in 'Coughee jar' and 'Packet in': a roadshow. PMID- 1624305 TI - The meaning of health promotion. PMID- 1624306 TI - Caring for the carers. PMID- 1624307 TI - MPs boost midwives role but warn on threat to neonatal care. AB - Midwives received a boost for their profession with the house of commons' second health committee report on maternity services. If MPs get their way midwives will hold their own caseloads, recommend whether pregnant women should be seen by an obstetrician, and play a greater part in referring women to hospital. Women should be seen by fewer professionals with greater continuity of care, says the report. A midwife known to the family should be the key worker supervising labour -a role eroded over the years with the shift away from home births and small maternity units to larger institutions and a doctor-dominated system. But MPs also issued a stern warning about the threat the NHS changes present to effective neonatal care of at risk babies. PMID- 1624309 TI - HIV infection: the issues for women and children. AB - HIV is now a worldwide pandemic, affecting some ten million adults and one million children--the overwhelming majority from sub-Saharan Africa. In Africa equal numbers of men and women are infected: in Europe just ten per cent of all cases of Aids are among women and two per cent among children. PMID- 1624308 TI - A landmark for people with AIDS. PMID- 1624310 TI - Women, AIDS and reproduction. AB - Relatively little has been written about how Aids affects women. When women are mentioned it is primarily as carers of people with Aids or as possible transmitters of the HIV virus, with the focus largely on prostitutes and pregnant women. The concern overwhelmingly is about how to protect the health of men and children, writes Diane Richardson. Here she examines the implications of Aids and HIV infection for women's health and reproductive rights. PMID- 1624311 TI - Sexuality and sexual health: an issue for community nurses. AB - Kate Butcher, health promotion worker in Calderdale, outlines the philosophy behind her work on sexual health. She argues that even in areas with a low incidence currently of people who are HIV positive, work on sexual health and sexuality by community nurses is a crucial aspect of health promotion activity. PMID- 1624312 TI - ME: is it a genuine disease? AB - Myalgic encephalomyelitis (ME) is a postviral syndrome whose dominant clinical features are exercise-induced muscle fatigue, disturbances in cognitive functioning and symptoms of overactivity of the autonomic nervous system. The syndrome tends to affect previously fit young adults between the ages of 20 and 40 but no age group is excluded. One recent epidemiological survey suggested a prevalence rate of 1.3 per 1000 adults, with females outnumbering males by 1.8:1. ME is currently the subject of intense medical (and media) debate, especially over its pathophysiology and management. It has also become known as the postviral/chronic fatigue syndrome (PVFS/CFS). PMID- 1624313 TI - Health visiting on a playbus: a community approach. AB - Inappropriate and overcrowded housing, poverty and lack of social support can affect the health and development of young children and their mothers. Such factors may prevent those families who most need health resources from using them. Rosalind Edwards and Stephanie Ramsey describe a project that attempts to encourage the use of health-related information by families with young children through taking an inter-agency and community-based approach. PMID- 1624314 TI - From claimant to customer. PMID- 1624315 TI - Unity in action. PMID- 1624316 TI - Taking the early way out. AB - Health visitors and school nurses forced to take time off sick need to know their pay and leave entitlements. Some may be contemplating--or coming under pressure to take--early retirement on grounds of ill-health. Here we look at the issues of long-term sick leave and early retirement. PMID- 1624317 TI - Health gain versus equity. AB - A new organisation, the Association for Public Health, has just been formed 'to help deliver real health gain for the population'. Alex Scott-Samuel suggests that the concept of 'health gain' is counter to health equality and needs wider debate. PMID- 1624318 TI - Ehlers-Danlos syndrome support group. PMID- 1624319 TI - Thinking as a profession. PMID- 1624320 TI - Punished for caring. PMID- 1624321 TI - 'Jump the gun' call. PMID- 1624322 TI - Twins in the family. AB - The key role of the health visitor in supporting families with multiple births was highlighted in the recent OPCS study Three, four or more. JUDI LINNEY, president of the Twins and multiple births association (TAMBA), outlines the health visitor's role in these circumstances. PMID- 1624323 TI - Supporting parents who wish to breastfeed twins. AB - Parents expecting twins need special support from health visitors to prepare them for the changes to their lives. A sound knowledge of the mechanics of breastfeeding and an empathetic understanding of their hopes and fears will prepare them for the months ahead, writes Alison Spiro. Health visitors may also be able to mobilise statutory and voluntary resources in the community to provide extra practical or emotional help. PMID- 1624324 TI - Community mothers: trick or treat? AB - To many health visitors they are a threat. To others they are a unique and invaluable resource. Cath Jackson talks to the health visitors and women involved in two projects pioneering community mother programmes in England. PMID- 1624325 TI - Towards a child health audit. AB - Child care can be improved by using a child health summary card, writes Sheila Jeffries. This would highlight the common needs of all children and their families, the special needs of certain types of families and the evaluation of methods employed. Additionally this scheme would provide data to help define the purpose of the work of the health visitor and school nurse. PMID- 1624326 TI - Education for school nurses. PMID- 1624327 TI - A checklist of benefit options. PMID- 1624328 TI - Unnatural selection. PMID- 1624329 TI - Health promotion in the global village. PMID- 1624330 TI - The village that refused to die. PMID- 1624331 TI - It could be ME. PMID- 1624333 TI - Livestock Conservation Institute supports AVMA legislative initiative. PMID- 1624332 TI - Confronting cosmetic surgery: cropping and docking not clear-cut issues. PMID- 1624334 TI - Ethical considerations in clinical research. PMID- 1624335 TI - Smorgasbord of activities. PMID- 1624336 TI - Diagnosis of copper deficiency in cattle. PMID- 1624337 TI - Some legal implications in biotechnology. PMID- 1624338 TI - Urine cortisol:creatinine ratio as a screening test for hyperadrenocorticism in dogs. AB - A urine cortisol:creatinine (c:c) ratio, determined from a free-catch morning sample, was evaluated in each of 83 dogs as a screening test for hyper adrenocorticism. The dogs evaluated were allotted to 3 groups, including 20 healthy dogs, 40 dogs with confirmed hyperadrenocorticism (HAC), and 23 dogs with polyuria and polydipsia not attributable to HAC (polyuria/polydipsia group; PU/PD). Overlap in the urine c:c ratios (mean +/- SEM), comparing results from the healthy dogs (5.7 x 10(-6) +/- 0.9) with those from the HAC dogs (337.7 x 10( 6) +/- 72.0) was not found. However, 11 (64%) of the 18 values from the PU/PD dogs (42.6 x 10(-6) +/- 9.4) were above the lowest ratio in the HAC group and 50% of the HAC group had a urine c:c ratio below the highest value in the PU/PD group. When the mean urine c:c ratio (+/- 2 SD) for the group of healthy dogs was used as a reference range, 100% of the HAC dogs and 18 (77%) of 23 dogs in the PU/PD group had abnormal urine c:c ratios. The sensitivity of the urine c:c ratio to discriminate dogs with HAC was 100%. The specificity of the urine c:c ratio was 22% and its diagnostic accuracy was 76%. On the basis of our findings, a urine c:c ratio within the reference range provides strong evidence to rule out HAC. However, abnormal urine c:c ratios are obtained from dogs with clinical diseases other than HAC. Therefore, measurement of a urine c:c ratio should not be used as the sole screening test to confirm a diagnosis of HAC. PMID- 1624339 TI - Determination of the number of mast cells in lymph node, bone marrow, and buffy coat cytologic specimens from dogs. AB - Cytologic samples of popliteal lymph node, proximal femoral bone marrow, and the buffy coat fraction of blood were obtained from 56 dogs. The number of mast cells on 1 slide of each sample was determined by microscopic examination. Eleven of 46 slides of lymph node aspirate contained mast cells (range, 1 to 16; mean, 6.4; median, 5 mast cells/slide). Fifty-one bone marrow aspirate slides were evaluated. Two of these contained a single mast cell. None of the 53 buffy coat smear slides examined contained any mast cells. These results indicated that in clinically normal dogs, a few to several mast cells may be encountered in smears of lymph node aspirate, mast cells are rare in smears of bone marrow aspirate, and mast cells are absent from smears of buffy coat. PMID- 1624340 TI - Evaluation of biocompatible osteoconductive polymer as an orthopedic implant in dogs. AB - The biocompatibility and osteoconductive properties of biocompatible osteoconductive polymer (BOP), a synthetic implant, were evaluated. Bilateral oval cortical defects (1 x 2 cm) were made in the lateral subtrochanteric area of the proximal portion of the femur in 16 dogs that later were treated with BOP fiber (n = 16) or autogenous cancellous bone (n = 11), or were not treated (n = 5). The BOP block was attached extraperiosteally to the proximal portion of the humerus in 6 dogs. Radiographic assessment of surgery sites was performed at 4 week intervals, and histologic evaluation was performed at 4, 8, 16, and 24 weeks after surgery. Radiographic signs of bone healing were not observed in defects treated with BOP fiber. Defects treated with cancellous bone or not treated had radiographic signs of progressive bone ingrowth. Radiographic evidence of periosteal new bone formation near control and BOP-treated defects was observed 4 weeks after surgery; increased periosteal reaction was associated with BOP fiber. This new bone had resorbed by week 24, except bone adjacent to BOP fiber, where continued periosteal reaction was apparent. Histologic evidence of bone formation was observed extending to, but not incorporating, BOP fibers. The BOP fibers became surrounded by a fibrous capsule, and fibrovascular connective tissue infiltrated between and into BOP fibers, but minimal bone formation incorporated the BOP material during the follow-up period. During that time, active periosteal new bone formation was evident adjacent to the BOP fibers. Defects treated with cancellous bone or not treated healed by ingrowth of cancellous bone during the first 12 weeks after surgery and by reformation of the lateral cortical wall by week 24. The BOP blocks became surrounded by a fibrous capsule, but connective tissue or bone ingrowth into BOP blocks was not observed. Results indicate that BOP is not osteoconductive within a 6-month time frame when used in subtrochanteric femoral defects or when placed extraperiosteally on the proximal portion of the humerus of clinically normal dogs. PMID- 1624341 TI - Anesthetic management of ostriches. AB - We evaluated and characterized several anesthetic induction protocols used to facilitate intubation and anesthetic maintenance with isoflurane in 7 adult ostriches and 1 juvenile ostrich. Induction protocols included IV administration of zolazepam/tiletamine, IV administration of diazepam/ketamine with and without xylazine, IV administration of xylazine/ketamine, IM administration of carfentanil or xylazine/carfentanil, and mask induction with isoflurane. General anesthesia was maintained with isoflurane in 100% oxygen for various procedures, including proventriculotomy (6 birds), tibial (1 bird) or mandibular (1 bird) fracture repair, and drainage of an iatrogenic hematoma (1 bird). Heart rate and respiratory rate varied greatly among birds. The arterial blood pressure values recorded from 6 of the birds during maintenance of general anesthesia were higher than values recorded for most mammalian species, but were comparable to values reported for awake chickens and turkeys. PMID- 1624342 TI - Health risks of housing small psittacines in galvanized wire mesh cages. AB - Each week over a 6-week period, 80 adult cockatiels (Nymphicus hollandicus) of either gender were dosed orally with fine particles of pure zinc or galvanized coating removed from welded wire mesh. At dosage of 32 mg/wk, all birds became severely ill and either died or were euthanatized within 2 weeks. Dosage of 2 mg/wk induced chronic illness marked by dullness, weight loss, and intermittent excretion of greenish droppings. Necropsy findings were unremarkable, except for signs suggestive of impaired gastrointestinal tract motility and histologic degenerative changes associated with focal mononuclear infiltration in the liver, kidneys, and pancreas. Tissue, especially pancreatic, contents of zinc were markedly high. Pure zinc was as toxic as galvanizing zinc. White rust, an oxidation product, also was toxic. The galvanized coating on cages and flights must be carefully wirebrushed and examined before housing psittacine birds. PMID- 1624343 TI - Mammary adenocarcinoma in four mares. AB - Mammary gland adenocarcinoma in 4 horses was characterized by firm swelling of the gland and serosanguineous discharge from the teat orifice. Two of the mares had ulcerative lesions of the mammary gland. Palpation of the affected gland typically elicited signs of pain. Diagnosis was assisted by cytologic evaluation of the fluid discharge, but definitive diagnosis was based on histologic examination. Treatment included mastectomy and lymphadenectomy. PMID- 1624344 TI - Immunotherapy of periocular squamous cell carcinoma with metastasis in a pony. AB - A 5-year-old Pony of America mare was referred for evaluation of inflamed upper and lower right eyelids. Squamous cell carcinoma of the eyelids and ulcerative keratitis secondary to self-trauma were diagnosed. Initial treatment of the eyelid neoplasia with 2 applications of cryotherapy failed to resolve the lesions, and immunotherapy with bacillus of Calmette-Guerin (BCG) was instituted. Multiple injections of BCG over a 17-week period resulted in progressive shrinkage of the tumor mass, but regional metastasis to the ipsilateral submandibular lymph node occurred. Six months later, ocular neoplastic lesions were not evident, and the lymph node had regressed in size. Eighteen months after the diagnosis of metastatic disease, signs of recurrence were not noticed in either the primary or secondary tumor sites. Squamous cell carcinoma of the equine eyelid historically carries a poor prognosis for resolution. Immunotherapy for equine ocular squamous cell carcinoma should be considered as a treatment alternative to cryosurgery, radiotherapy, hyperthermy, and CO2 laser ablation, especially in cases involving the eyelid. PMID- 1624345 TI - Steroid hepatopathy in a horse with glucocorticoid-induced hyperadrenocorticism. AB - Steroid hepatopathy was diagnosed in a horse with glucorticoid-induced hyperadrenocorticism on the basis of anamnesis, serum biochemical data, and histologic findings of hepatic biopsy. Initially, clinical signs of polyuria, polydypsia, and muscular degeneration were seen. The horse developed laminitis during hospitalization. PMID- 1624346 TI - Septic metritis secondary to torsion of a pedunculated uterine fibroleiomyoma in a filly. AB - A 2-year-old Arabian filly was referred for evaluation of a serosanguineous vaginal discharge. Palpation per rectum revealed a large, fluid-filled uterus and a uterine mass. The filly developed septic metritis and secondary laminitis as a result of torsion and necrosis of a pedunculated uterine mass. Ovariohysterectomy was performed. The entire cervix was removed with the uterus. Gross examination of the excised uterus revealed 3 intraluminal masses. Histologic evaluation identified the tumors as fibroleiomyoma. The filly recovered completely, and there was no recurrence of the tumor. PMID- 1624347 TI - Testicular feminization syndrome in a mare. AB - Testicular feminization syndrome was diagnosed in a mare with aggressive, stallion like behavior and a history of infertility. She was found to have a high baseline testosterone concentration suggesting that testicular tissue was present, and ovarian-like structures examined by use of transrectal ultrasonography had the appearance typical of testicular tissue. Although her external female genitalia appeared normal, her vagina ended in a blind sac, and no cervix or uterus were identified. Surgery was performed, and structures removed from the abdominal cavity were determined to be hypoplastic testicles. Removal of the testicular tissue resulted in complete resolution of her aggressive behavior. Chromosomal evaluation revealed that the mare had 64X,Y (normal male) karyotype. Testicular feminization syndrome is a condition characterized by insensitivity of reproductive tissues to androgens during development because of an abnormality in androgen receptors. This androgen insensitivity results in development of normal external female genitalia, with high testosterone concentrations being released from developing testicles. Testicular feminization syndrome has not been commonly diagnosed in horses, but should be considered as a differential diagnosis for overly aggressive mares with a history of infertility. PMID- 1624348 TI - Conservative management of uroperitoneum in a gelding. AB - Uroperitoneum as a sequela to urethral calculus in an adult gelding was successfully managed by use of subischial urethrotomy and abdominal drainage. Necrosis of bladder mucosa was seen endoscopically, but a tear or rupture was never identified. Peritonitis developed but was controlled with antibacterial treatment. Although uroperitoneum is usually a sequela to bladder rupture and the ideal treatment is surgical repair, conservative management may be warranted in selected cases. PMID- 1624349 TI - Arthroscopic removal of an osteochondral fragment from the caudal pouch of the lateral femorotibial joint in a colt. AB - An osteochondral fragment was removed from the caudal pouch of the lateral femorotibial joint in a 2-year-old Trakehner colt by use of arthroscopic surgery and a lateral approach. The approach to this aspect of the femorotibial joints was developed in another horse. The fragment was not attached and resembled an osteochondritis dissecans lesion. The intermittent lameness associated with the fragment resolved after surgical removal. A positive response to diagnostic anesthesia of the femorotibial joint in the absence of a confirmed diagnosis (following radiographic and arthroscopic evaluations of the other aspects of the stifle joint) is an indication for arthroscopic exploration of the caudal pouches of the femorotibial joints of stifles in horses. PMID- 1624350 TI - Tracheal obstruction from tracheal collapse associated with pneumonia in a horse. AB - A 20-month-old Quarter Horse stallion was admitted for evaluation of labored breathing, honking cough, and bilateral epistaxis that were caused by pneumonia and collapsed trachea. A transtracheal aspiration revealed highly cellular, serosanguineous fluid. Radiography revealed a patchy alveolar pattern and a narrowed tracheal lumen. Endoscopy confirmed narrowing of the tracheal lumen. Streptococcus zooepidemicus was isolated on culture of the transtracheal aspirate. The horse responded to penicillin treatment, and the tracheal collapse improved endoscopically after 4 days, with complete recovery within 1 year. Tracheal collapse has been reported to be a disease of older horses associated with degenerative cartilage. The findings in the horse of this report suggested that tracheal collapse may result from inflammation secondary to pneumonia and, therefore, may be reversible. PMID- 1624351 TI - Repair of a proximal diaphyseal femoral fracture in a calf, using intramedullary pinning, cerclage wiring, and external fixation. AB - Repair of a comminuted, spiral oblique, proximal diaphyseal femoral fracture in a 7-day-old calf was achieved by use of an intramedullary pin, cerclage wires, and external fixator. Six stainless steel wires were used for full cerclage to secure a long butterfly fragment and multiple incomplete and complete nondisplaced fragments to the femur in order to create 2 principal fragments. Axial alignment and resistance to bending was provided by a round, double-pointed, end-threaded intramedullary pin (6.35 mm in diameter), which was inserted in a retrograde fashion. A type-1, double-connecting-bar external fixator, using 4 round pins (4.8 mm in diameter), was used to provide supplemental stabilization against shear and torsional forces. At 45 days after surgery, healing at the fracture site was seen on radiography of the limb, and the external fixator was removed. Eight months after surgery, the calf had a normal gait. PMID- 1624352 TI - Cholangiohepatitis in a dog. AB - Cholangiohepatitis was diagnosed in a dog with a 4-day history of anorexia, vomiting, fever, and icterus. Additional findings included signs of depression, dehydration, hepatosplenomegaly, and abdominal discomfort. Exploratory laparotomy was performed, and specimens of liver, spleen, and bile were obtained. Histologic evaluation of liver and spleen revealed acute, suppurative cholangio-hepatitis and splenitis, respectively. Cultures of liver and bile yielded Klebsiella sp. The dog responded to rehydration and intravenous administration of chloramphenicol. Although uncommon, cholangiohepatitis should be suspected in dogs with anorexia, fever, vomiting, icterus, and signs of abdominal discomfort. Definitive diagnosis requires bacterial cultures of liver and bile. Administration of an appropriate antibiotic should resolve clinical signs. PMID- 1624353 TI - Intermittent gastric dilatation after gastropexy in a dog. AB - Gastroperitoneal adhesions, which developed after tube gastrostomy in a 3-year old dog, caused an inverted L configuration of the pyloric antrum and duodenum, resulting in periodic episodes of gastric dilatation. The dog had undergone tube gastrostomy for treatment of gastric dilatation/volvulus, but gastropexy adhesions broke down 27 months later, necessitating a second pexy procedure. Adhesions then developed, constricting gastric outflow and trapping gas in the stomach and proximal duodenum. When the ventral row of adhesions was surgically dissected, the angle between the pyloric antrum and the duodenum was straightened, facilitating flow of digesta. Gastropexy rarely causes the degree of adhesion formation and the complications reported in this dog. PMID- 1624354 TI - Closure of the iliac crest ossification center in dogs: 750 cases (1980-1987). AB - Radiographs of 750 dogs were examined to determine whether the iliac crest ossification center was open or closed. The center was closed in most dogs by 2 years of age. Eighteen percent of dogs greater than or equal to 10 years old had open iliac crest ossification center; 10% of dogs greater than or equal to 14 years old had open iliac crest ossification center. Closure of the iliac crest ossification center is extremely variable and, in many dogs, occurs at later age than has been previously reported. PMID- 1624355 TI - Lymphocytic/plasmacytic gastroenteritis in cats: 14 cases (1985-1990). AB - Over a 5-year period, lymphocytic/plasmacytic gastroenteritis was diagnosed in 14 cats. Purebred cats were affected significantly (P less than 0.025) more often than nonpurebred cats. Mean age at onset of clinical signs was 6.8 years (range, 1 to 13 years); 11 cats were male. Vomiting and weight loss, each reported in 10 of 14 cats, were the most common clinical signs. Diarrhea was reported in 7 of 14 cats. Alopecia was found in 4 of 14 cats. High hepatic enzyme activities and low plasma protein concentrations were frequent biochemical findings. Hyperemia, hemorrhage, and a roughened or "cobblestone" mucosa were visualized by endoscopy in only 2 of 8 cats with duodenal disease and in 2 of 5 cats with gastric disease. Lymphocytic/plasmacytic inflammation was detected in biopsy specimens from the stomach or duodenum or both in all cats; the duodenum was affected most commonly. Degree of inflammation frequently varied among gastric, duodenal, and colonic specimens from the same cat. Glucocorticoid treatment and dietary management adequately controlled clinical signs in 7 cats, but treatment was ineffective in 6 cats, 5 of which were euthanatized because of severity of clinical signs. PMID- 1624356 TI - Actinomycetales infections in slender-horned gazelles: six cases (1987-1989). AB - Disseminated Actinomycetales infections were diagnosed in 6 slender-horned gazelles at a zoologic park over a 17-month period. Nocardia and Mycobacterium spp were isolated. Possible predisposing causes leading to infection were investigated. Environmental contamination where the gazelles were housed was not high, and other breeds of gazelles at the park did not become infected, indicating that environmental exposure was not the sole factor involved. Information gathered from questionnaires sent to other zoologic parks and personnel communications indicated that this was not an isolated incident. Investigation into the genetic lineage of the gazelles revealed substantial inbreeding in prior generations. These findings suggested inbreeding may have been an important predisposing factor leading to infection. Careful scrutiny to ensure maximal heterozygosity of future breedings is warranted. PMID- 1624357 TI - Blindness associated with toxoplasmosis in canaries. AB - Seven of 30 canaries in an aviary in New Zealand developed ophthalmic problems. Clinically, 5 birds had unilateral and 2 birds had bilateral lesions characterized by conjunctivitis, crusty exudates on eyelids, and collapse of the eyeball. Microscopic lesions in 12 of 14 eyes examined included inflammation of the choroid and retina, with osseous replacement of the globe in some. Numerous Toxoplasma gondii tachyzoites were seen in the detached retina and vitreous humor of acutely affected birds. The diagnosis of toxoplasmosis was confirmed by immunohistochemical staining with T gondii antiserum. Affected birds had encephalitis, and T gondii was localized in the brains of these by immunohistochemical examination and by use of bioassays in mice. Toxoplasmosis should be considered in differential diagnosis of ophthalmitis in canaries. PMID- 1624358 TI - Treatment of lead poisoning in wild geese. AB - Twenty-seven wild geese (Anser albifrons) suffering from lead poisoning caused by ingestion of lead shot were treated with disodium calcium ethylenediaminetetraacetate. The concentration of lead in blood ranged from 0.4 to 23.0 micrograms/ml, with a mean concentration of 5.6 micrograms/ml. In 22 of the birds, 1 to 48 lead pellets (mean, 10.5 pellets/bird) were seen on radiographs of their gizzards. Eleven of 27 birds recovered 3 to 8 weeks after the initiation of treatment. In the birds that recovered, the lead pellets were rapidly eroded as the birds recovered their appetites in response to treatment, and disappeared radiographically between treatment days 17 and 52. The birds that did not survive died within 4 weeks, despite decreased concentrations of lead in blood. Of these 16 birds, 15 had radiographic evidence of impaction of the proventriculus at the first examination and no evidence of resolution of the impaction at the time of death. In contrast, only 2 of the 11 geese that recovered had impaction of the proventriculus at the time of admission. Thus, the condition of the proventriculus seems to be the first consideration to evaluate in the prognosis of lead poisoning in geese. PMID- 1624359 TI - What is your diagnosis? Osteomyelitis of the distal portion of the radius, with associated soft tissue swelling. PMID- 1624360 TI - Sporeamicin A, a new macrolide antibiotic. I. Taxonomy, fermentation, isolation and characterization. AB - Sporeamicin A, a novel antibiotic, was isolated from the culture filtrate of an actinomycete. The producing organism, strain L53-18, was taxonomically assigned as a species of the genus Saccaropolyspora. The antibiotic was extracted with chloroform and was then purified by crystallization. It was obtained as colorless prisms from ethanolic solutions. Sporeamicin A exhibited a strong UV absorption peak at 276 nm. The molecular formula of sporeamicin A was determined to be C37H63NO12. PMID- 1624361 TI - Sporeamicin A, a new macrolide antibiotic. II. Structure determination. AB - Structure of a novel antibiotic, sporeamicin A (SRM-A), was determined by a combination of spectroscopic and X-ray crystallographic studies. SRM-A has a unique structure containing a 2,3-dihydro-3-oxofuran moiety as part of a 14 membered macrolide ring. PMID- 1624362 TI - Sporeamicin A, a new macrolide antibiotic. III. Biological properties. AB - Sporeamicin A is a new erythromycin-type antibiotic isolated from a species of Saccharopolyspora. It was active in vitro against a wide variety of Gram-positive bacteria. In vitro studies indicated that the sporeamicin A was stable in the presence of human serum, although it was bound to serum proteins. Sporeamicin A was effective in the mouse protection test against Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae. Sporeamicin A attained higher plasma and tissue levels in the rat than did erythromycin stearate. PMID- 1624363 TI - Deoxymulundocandin--a new echinocandin type antifungal antibiotic. AB - A new echinocandin type antifungal antibiotic, deoxymulundocandin, C48H77N7O15, was isolated from the culture filtrate and mycelia of a fungal culture, Aspergillus sydowii (Bainier and Sartory) Thom and Church var. nov. mulundensis Roy (Culture No. Y-30462). The structure was established by comparative GC-MS analyses of the derivatized acid hydrolysates of deoxymulundocandin and mulundocandin as well as by the high field NMR experiments (COSY, NOESY and DEPT). PMID- 1624364 TI - Macrolactams: a novel class of antifungal antibiotics produced by Actinomadura spp. SCC 1776 and SCC 1777. AB - Three novel antifungal antibiotics, Sch 38518, Sch 39185 and Sch 38516 were isolated from the fermentation broths of two actinomycetes identified by chemical, morphological and physiological analysis as a new species of Actinomadura. The compounds were isolated from broth by solvent extraction and purified by silica gel chromatography. Physico-chemical properties, mass spectral analysis, IR and UV suggested the compounds were similar. Sch 38518 and Sch 39185 have a molecular formula of C25H48N2O5. 1H NMR, 13C NMR and hydrolysis indicated the aglycones were identical, however the compounds differed in containing isomeric sugar moieties. Sch 38518 contains mycosamine while Sch 39185 contains 3,6-dideoxy-3-amino-L-talopyranose. Sch 38516 has a molecular formula of C24H46N2O5 and is a lower homolog of Sch 39185. The three compounds, Sch 38518 (1), Sch 39185 (2), and Sch 38516 (3) exhibit similar activity against Candida spp. with geometric mean MICs of 1.81, 2.00 and 0.91 micrograms/ml, respectively. PMID- 1624365 TI - Macrolactams: two novel homologous series of compounds produced by Actinomadura sp. SCC 1778. AB - Eight antifungal compounds were identified from the fermentation of Actinomadura sp. SCC 1778. This culture produces four homologous compounds (C22H42N2O5 approximately C25H48N2O5) containing the sugar, mycosamine, and four homologous compounds (C22H42N2O5 approximately C25H48N2O5) containing the sugar, 3,6-dideoxy 3-amino-L-talopyranose. Five of the compounds identified were novel macrolactams. All these compounds exhibit antifungal activity against Candida spp. with geometric mean MICs ranging from approximately 1.0 micrograms/ml for the higher homologs to 30 micrograms/ml for the lower homologs. PMID- 1624366 TI - The squalestatins, novel inhibitors of squalene synthase produced by a species of Phoma. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activity. AB - During the screening of fungi for inhibitors of squalene synthase, Phoma sp. C2932 was found to produce three structurally related novel inhibitors. These compounds, designated the squalestatins, exhibited potent activity against both mammalian (rat liver) and fungal (Candida albicans) squalene synthase. Furthermore, they also had broad spectrum in vitro antifungal activity. PMID- 1624367 TI - The squalestatins, novel inhibitors of squalene synthase produced by a species of Phoma. II. Structure elucidation. AB - Three novel fungal metabolites 1-3 isolated from cultures of a Phoma sp. C2932, are potent and selective inhibitors of squalene synthase. Their structures have been determined by a combination of spectroscopic, X-ray crystallographic and chemical methods; these natural products incorporate the highly functionalised bicyclic core, [1S-(1 alpha, 3 alpha, 4 beta, 5 alpha, 6 alpha, 7 beta]-4,6,7 trihydroxy- 2,8-dioxabicyclo-[3.2.1]octane-3,4,5-tricarboxylic acid. PMID- 1624368 TI - C-13 beta-acyloxymilbemycins, a new family of macrolides. Discovery, structural determination and biological properties. AB - A family of novel milbemycins possessing C-13 beta-acyloxy substitution was produced by Streptomyces hygroscopicus ATCC 53718. These compounds were detected by HPLC diode array analysis and possess anthelmintic and ectoparasiticidal activity. The origin of the oxygen atom at C-13 is discussed. PMID- 1624369 TI - L-696,474, a novel cytochalasin as an inhibitor of HIV-1 protease. I. The producing organism and its fermentation. AB - A novel cytochalasin, L-696,474, (18-dehydroxy cytochalasin H) that inhibits HIV 1 protease was discovered in fermentations of a bark-inhabiting Ascomycete, Hypoxylon fragiforme. The product was first identified from extracts of an agar medium. Fermentation studies on a number of media indicated that the product can be made on several solid and liquid media. Optimum production was obtained from growth in a complex medium composed of glycerol, glucose, citrate, Ardamine, soybean meal, tomato paste, and inorganic salts. Other Hypoxylon spp., related species of Xylariales, and other fungi known to produce cytochalasins, were also surveyed for their ability to make L-696,474. Only one other Hypoxylon fragiforme isolate was found to make this novel cytochalasin; none of the other cultures surveyed made L-696,474 or any other compounds which inhibit HIV-1 protease. PMID- 1624370 TI - L-696,474, a novel cytochalasin as an inhibitor of HIV-1 protease. II. Isolation and structure. AB - A novel HIV-1 protease inhibitor, L-696,474 (C30H39NO4, 477), was isolated from the fermentations of the fungus Hypoxylon fragiforme (ATCC 20995, MF5511) and purified by silica gel chromatography followed by crystallization. Spectroscopic studies have shown the competitive inhibitor L-696,474 to be a novel cytochalasin. Two related novel cytochalasins were also isolated and had no effect on the enzyme. PMID- 1624371 TI - L-696,474, a novel cytochalasin as an inhibitor of HIV-1 protease. III. Biological activity. AB - L-696,474, an inhibitor of the HIV-1 protease, was discovered in extracts of the fungal culture Hypoxylon fragiforme (MF5511; ATCC 20995). L-696,474 is a novel cytochalasin with a molecular weight of 477 and an empirical formula of C30H39NO4. L-696,474 inhibited HIV-1 protease activity with an IC50 of 3 microM and the mode of inhibition was competitive with respect to substrate (apparent Ki = 1 microM). Furthermore, L-696,474 was not a slow-binding inhibitor. The inhibition due to L-696,474 was also independent of the HIV-1 protease concentration. L-696,474 was inactive against pepsin, another aspartyl protease; stromelysin, a zinc-metalloproteinase; papain, a cysteine-specific protease or human leucocyte elastase, a serine-specific protease. Two other novel cytochalasins (L-697,318 and L-696,475) isolated from the same culture were inactive against the HIV-1 protease. Commercially available cytochalasins B, C, D, E, F, H and J were inactive while cytochalasin A was as active as L-696,474 against the HIV-1 protease. PMID- 1624372 TI - A new anthelmintic cyclodepsipeptide, PF1022A. AB - The novel anthelmintic cyclodepsipeptide PF1022A was isolated from cultured mycelia of Mycelia Sterilia PF1022 (FERM BP-2671). It showed strong anthelmintic activities against Ascaridia galli in chickens. The structure of PF1022A was determined to be cyclo(D-lactyl-L-N-methylleucyl-D-3-phenyllactyl-L-N-meth ylleucyl-D-lactyl-L-N- methylleucyl-D-3-phenyllactyl-L-N-methylleucyl) by spectroscopic analyses and chemical studies. PMID- 1624373 TI - Studies on condensed-heterocyclic azolium cephalosporins. IV. Synthesis and antibacterial activity of 7 beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)- alkoxyiminoacetamido]-3-(condensed-heterocyclic azolium)methyl cephalosporins including SCE-2787. AB - The synthesis and in vitro antibacterial activity of 7 beta-[2-(5-amino-1,2,4 thiadiazol-3-yl)-2(Z)-alkoxyiminoacetami do] cephalosporins bearing various condensed-heterocyclic azolium groups at the 3 position in the cephalosporin nucleus are described. The thiadiazolyl cephalosporins showed good antibacterial activity against both Gram-positive and Gram-negative bacteria and the MICs of the thiadiazolyl cephalosporins against Pseudomonas aeruginosa was more potent than that of the corresponding 7 beta-[2-(2-aminothiazol-4-yl)-2(Z) alkoxyiminoacetamido]-3- (condensed-heterocyclic azolium)methyl cephalosporins. Also, the thiadiazolyl cephalosporins bearing (imidazo[1,2-b]-pyridazinium-1 yl)methyl groups at the 3 position showed antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Among the cephalosporins tested, 7 beta-[2-(5- amino-1,2,4-thiadiazol-3-yl)-2(Z)-methoxyiminoacetamido]-3 (imidaz o[1,2- b]pyridazinium-1-yl)methyl-3- cephem-4-carboxylate (4, SCE-2787) which exhibited the most potent antibacterial activity and the broadest antibacterial spectrum was selected as a parenteral cephalosporin candidate for further biological evaluation. PMID- 1624374 TI - Studies on condensed-heterocyclic azolium cephalosporins. V. Synthesis and antibacterial activity of 3-(condensed-triazolo-pyridinium, -pyrimidinium, and pyridazinium)-methyl cephalosporins. AB - As a part of our studies on cephalosporins bearing condensed-heterocyclic azolium methyl groups at the 3 position in the cephalosporin nucleus, we describe here the synthesis and antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)2(Z) methoxyiminoacetamido] cephalosporins (1-16, 7 beta-[2-(2-amino-5-chlorothiazol-4 yl)-2(Z)- methoxyiminoacetamido] cephalosporins (17,18) and 7 beta-[2-(5-amino- 1,2,4-thiadiazol-3-yl)-2(Z)-methoxyiminoacetamido) cephalosporins (19-23) containing a variety of condensed-heterocyclic triazolium methyl groups at the 3 position in the cephalosporin nucleus. These cephalosporins exhibited potent antibacterial activity, and it appears that condensed-heterocyclic triazolium as well as condensed-heterocyclic imidazolium rings are effective moieties for improving antibacterial activity and the spectrum of activity. Among the cephalosporins tested, 7 beta-[2-(2-aminothiazol-4-yl)-2(Z) methoxyiminoacetamido]-3-(5- methyl[1,2,3]triazolo-[1,5-alpha]pyridinium-1 yl)methyl-3-cephem-4- carboxylate (9) and 7 beta-[2-(2-aminothiazol-4-yl)-2(Z) methoxyiminoacetamido]-3-(6- methoxy[1,2,4]triazolo[1,5-alpha]pyridinium-1 yl)methyl-3-cephem-4- carboxylate (11) showed good antibacterial activity. PMID- 1624375 TI - Syntheses and activities of some bactobolin derivatives. AB - Some derivatives of bactobolin were prepared from bactobolin by dehydration or substitution reactions through tris(dimethylamino)alkoxyphosphonium salt formation. A derivative with low toxicity, 6-deoxybactobolin, showed moderate activity against Gram-positive and Gram-negative bacteria including methicillin resistant Staphylococcus aureus. PMID- 1624376 TI - Polymyxin B octapeptide and polymyxin B heptapeptide are potent outer membrane permeability-increasing agents. AB - Polymyxin B octapeptide (PBOP) and polymyxin B heptapeptide (PBHP) were found to be effective permeabilizers of the outer membrane of Escherichia coli and Salmonella typhimurium. PBOP was as effective as polymyxin B nonapeptide (PMBN), the known very potent permeabilizer. As low a PBOP concentration as 1 microgram/ml sensitized E. coli to rifampicin by a factor of 100. Three micrograms of PBOP per ml was sufficient to sensitize this target to all the other tested hydrophobic antibiotics (erythromycin, fusidic acid, clindamycin, and novobiocin) by a factor of 30. Only a slightly higher (3-fold) concentration of PBHP was required for a similar sensitizing effect. PMID- 1624377 TI - Biochemical studies on 2-deoxy-scyllo-inosose, an early intermediate in the biosynthesis of 2-deoxystreptamine. I. Chemical synthesis of 2-deoxy-scyllo inosose and [2,2-2H2]-2-deoxy-scyllo-inosose. AB - A practical preparative method for 2-deoxy-scyllo-inosose, the earliest key intermediate leading to 2-deoxystreptamine, was devised as a prerequisite to more detailed biochemical studies on the biosynthesis of 2-deoxystreptamine. [2,2-2H2] 2-Deoxy-scyllo-inosose was also synthesized through a modified Ferrier reaction. PMID- 1624378 TI - Biochemical studies on 2-deoxy-scyllo-inosose, an early intermediate in the biosynthesis of 2-deoxystreptamine. II. Quantitative analysis of 2-deoxy-scyllo inosose. AB - A practical quantitative analysis of 2-deoxy-scyllo-inosose by means of GC-MS selected-ion monitoring (SIM) was exploited in order to assay the enzymatic 2 deoxy-scyllo-inosose formation, the first stage of the 2-deoxystreptamine biosynthesis. Mass spectral fragmentations of 2-deoxy-scyllo-inosose tetra-O trimethylsilyl (TMS) ether was also investigated by the use of [2,2-2H2]-2-deoxy scyllo-inosose. PMID- 1624379 TI - Confirmation of in vitro synthesis of 2-deoxy-scyllo-inosose, the earliest intermediate in the biosynthesis of 2-deoxystreptamine, using cell free preparations of Streptomyces fradiae. PMID- 1624380 TI - Studies on the biosynthesis of bialaphos (SF-1293) 12. C-P bond formation mechanism of bialaphos: discovery of a P-methylation enzyme. AB - An enzymatic activity catalyzing P-methylation of N acetyldemethylphosphinothricin, a biosynthetic intermediate of the herbicide bialaphos, was detected in a cell extract of Streptomyces hygroscopicus SF-1293, a bialaphos producing organism. The gene coding for this P-methylation enzyme in the bialaphos biosynthetic gene cluster was also expressed in Streptomyces lividans. The methyl donor of the reaction was determined to be methylcobalamin. The P-methylation enzyme utilized both N-acetyldemethylbialaphos and N acetyldemethylphosphinothricin as substrates. PMID- 1624381 TI - WS-7338, new endothelin receptor antagonists isolated from Streptomyces sp. No. 7338. III. Structures of WS-7338 A, B, C and D and total synthesis of WS-7338 B. PMID- 1624382 TI - Studies on bottromycins. I. 1H and 13C NMR assignments of bottromycin A2, the main component of the complex. PMID- 1624383 TI - Synthesis and biological properties of FCE 25199, a new oral penem. PMID- 1624384 TI - Microbial conversion of milbemycins: 29-hydroxylation of milbemycins by genus Syncephalastrum. PMID- 1624385 TI - Chronotoxical study of gentamicin induced nephrotoxicity in rats. PMID- 1624386 TI - Isolation and characterization of sporeamicin B. PMID- 1624387 TI - The production of semduramicin by direct fermentation. PMID- 1624388 TI - The Garrod Lecture. Understanding the chemotherapy of tuberculosis--current problems. PMID- 1624389 TI - BSAC, third combined British Scandinavian Hellenic Conference, May 1991: immunotherapy of infectious disease. PMID- 1624390 TI - The binding of amikacin to macromolecules from the sputum of patients suffering from respiratory diseases. AB - Antibiotics bind to whole cystic fibrosis sputum, however, the composition of sputum varies from one patient to another, making the interpretation of binding studies difficult. This problem has been examined by standardizing the macromolecule concentration of sputum from 13 patients suffering from cystic fibrosis, chronic bronchitis or bronchiectasis and adding amikacin to the sputum components. Also binding to fractions of sputum was studied before and after treatment with DNase or chondroitinase. These studies indicated that the degree of amikacin binding is dependent on the DNA concentration and the presence of acidic mucins. PMID- 1624391 TI - Antibacterial properties of SCE-2787, a new cephem antibiotic. AB - The in-vitro antibacterial properties of SCE-2787, a new semi-synthetic parenteral cephalosporin, were evaluated by comparing its affinities for penicillin-binding proteins (PBPs), its bactericidal activity and its effects on morphology with those of ceftazidime, cefpirome and E-1040. SCE-2787 and cefpirome had higher affinities for PBPs 1 and 2 of Staphylococcus aureus, and a more potent anti-staphylococcal activity, than ceftazidime and E-1040. All four antibiotics had similar activity against Escherichia coli, and showed similar affinities for PBP 3 of this organism. SCE-2787, ceftazidime and E-1040 were more potent than cefpirome against Pseudomonas aeruginosa, and showed higher affinities for the P. aeruginosa PBP 3. The wide-spectrum antibacterial activity of SCE-2787 can be explained, in general, by its high affinities for PBPs, SCE 2787, at half its MIC level or higher, was bactericidal against all the bacterial strains examined, as were the other antibiotics tested. Exposure of S. aureus to SCE-2787 resulted in the formation of cell walls with irregular septa which subsequently thickened and collapsed. Elongation was the major morphological change of E. coli and P. aeruginosa cells treated with SCE-2787. E. coli cells were converted to 'ghosts', infrequent in P. aeruginosa, after prolonged incubation with higher concentrations of SCE-2787. PMID- 1624392 TI - Antimicrobial resistance in Haemophilus influenzae from England and Scotland in 1991. AB - Twenty-two laboratories in England and Scotland sent 2212 clinical isolates of Haemophilus influenzae to The London Hospital Medical College (LHMC) between 1 January and 31 March 1991. After confirmation of identity, the prevalence of resistance was determined and compared with results from previous similar surveys. beta-Lactamase was produced by 8.3% of non-capsulate isolates and 21% of 52 type b isolates; both figures were higher than the 6% and 18% figures recorded, respectively, in 1986. There was an increase in the prevalence of non beta-lactamase-mediated diminished susceptibility to ampicillin (5.8%) and co amoxiclav (6.1%) compared with 1986 (4%). Whereas fewer H. influenzae isolates were resistant to tetracycline (1.4%) or chloramphenicol (0.8%), there was an increase in resistance to trimethoprim (6.8%) and to sulphamethoxazole (16.9%) compared with 1986 (4.2% and 3.5% respectively). In addition, 95 isolates (4.3%) were resistant to both of these anti-folate antimicrobials. Six isolates (one type b from CSF) were resistant to all drugs tested, except for co-amoxiclav. Overall, the results demonstrated that changes have occurred in the last decade in England and Scotland, such that H. influenzae isolates are increasingly likely to be resistant to ampicillin, co-amoxiclav and co-trimoxazole. PMID- 1624393 TI - Activity of rifapentine against Mycobacterium avium infection in beige mice. AB - The activity of rifapentine (MDL 473) was evaluated in the beige (C57BL/6J bgj/bgj) mouse model of disseminated Mycobacterium avium infection. Approximately 10(7) cfu of M. avium, serotype 1, were given iv. Seven days later treatment was started with intraperitoneal rifapentine at 20 mg/kg of body weight. Treatment was given daily for five days followed by twice weekly for three weeks. The mice were killed two days after the last dose. Spleens, livers and lungs were homogenized and cfu/organ determined. Analysis of variance and Tukey honestly significant difference tests indicated that rifapentine reduced cfu in each of the organs compared with untreated controls. A dose-response experiment was performed with a daily rifapentine dose of 10, 20 or 40 mg/kg administered intraperitoneally. Dose-related reductions in cfu counts were observed in each of the organs. The activity of oral rifapentine at 20 mg/kg was demonstrated in a comparative experiment with rifampicin at 20, 40 or 60 mg/kg. Rifapentine significantly reduced cfu counts in organs compared with rifampicin. Rifapentine should be considered for further evaluation in the treatment of M. avium complex infection in humans. PMID- 1624394 TI - Development of resistance during ceftazidime and cefepime therapy in a murine peritonitis model. AB - Resistance emerging after ceftazidime or cefepime therapy was investigated in a peritonitis model. Mice were given a peritoneal challenge (10(8) cfu plus talcum) and treated by either antibiotic (50 mg/kg/dose, which produced similar antibiotic concentrations in peritoneal fluid in both cases). After one or three doses, resistance never developed in Serratia marcescens or Citrobacter freundii infections. After Enterobacter cloacae and Pseudomonas aeruginosa challenge, ceftazidime selected more resistance (21/36 cases) than did cefepime (1/36 cases). In mice challenged with resistant strains selected by ceftazidime therapy, cefepime (six doses) successfully treated 7/18 E. cloacae infections but 0/18 P. aeruginosa infections; ceftazidime was never effective. Neither cefepime nor ceftazidime cured mice infected with the resistant strain selected by cefepime. MICs were poor predictors of further emergence of resistance in mice inoculated with strains classified as susceptible, but antibiotic-containing agar gradients plated with a high inoculum (10(8) cfu) allowed better prediction. In selected clinical situations, cefepime may be preferable because it may be associated with less frequent emergence of resistance. PMID- 1624395 TI - Sampling time for serum gentamicin levels. AB - A survey in 53 UK hospitals showed that 44% of clinical microbiologists recommended post-dose serum gentamicin concentrations to be measured at less than 40 min after an iv bolus dose. Serum gentamicin concentrations were measured in ten patients following bolus iv and im injections. Distribution of the drug occurred for up to 45 min following iv doses and maximum serum concentrations occurred at 45 to 60 min after im injection. The data validate current guidelines to sample at 60 min post bolus iv and im doses. Earlier sampling after iv bolus injections may result in significantly higher gentamicin concentrations, leading to potential interpretive errors of clinical significance. PMID- 1624396 TI - Penetration of pefloxacin into gynaecological tissues. AB - In a prospective pharmacokinetic study, the plasma and tissue concentrations of pefloxacin were studied. Twelve patients were premedicated with pefloxacin 400 mg bd orally for three days followed by 400 mg iv preoperatively. Tissue samples during surgery were taken from the skin, peritoneum, ovary, myometrium and fallopian tubes. Pefloxacin concentrations were measured by high performance liquid chromatography with fluorescence detection. The mean elimination half-life of pefloxacin was 11.3 h, the mean residence time (MRT) was 15.8 h and the apparent volume of distribution 1.52 +/- 0.525 L/kg. Pefloxacin concentrations in myometrium, ovary and fallopian tubes exceeded four- to six-fold the corresponding plasma concentrations 3.5 h after the last drug intake. At the start of surgery, about 2.5 h after the last dose, the skin/plasma concentration ratio and the peritoneum/plasma concentration ratio were 2.65 and 1.18, respectively. At the end of surgery, these ratios were 4.65 and 1.5. The tissue concentrations exceeded the MIC90 for most common pathogens implicated in gynaecological infections. PMID- 1624397 TI - A novel plasmid-mediated extended-spectrum beta-lactamase not derived from TEM- or SHV-type enzymes. PMID- 1624398 TI - beta-Lactamases and susceptibility phenotypes to beta-lactam antibiotics in Escherichia coli strains. PMID- 1624399 TI - In-vitro activity of LY264826, an investigational glycopeptide antibiotic, against gram-positive bloodstream isolates and selected gram-negative bacilli. PMID- 1624401 TI - Tetracycline resistance in Bacteroides ureolyticus. PMID- 1624400 TI - In-vitro antimicrobial activity of the penem BRL-42715, alone and in combination with ampicillin, against respiratory tract pathogens. PMID- 1624402 TI - Intraperitoneal penetration of FCE 22101. PMID- 1624403 TI - Communication abilities and Rett syndrome. AB - Investigated 6 girls with Rett syndrome (RS), ages between 2 and 13 years, to provide comprehensive descriptions of their communicative behaviors. Previous studies have not focused on communicative competence nor on the intentionality of the language used by children with RS. This study concluded that all members of the group investigated were at a preintentional level of communication. Intentional communication has previously been reported to develop in normally developing and intellectually disabled children attaining Piagetian Sensorimotor Stage V in Means-End behavior. The present study also investigated the cognitive performance of the group. We concluded that the preintentional level of communication noted was consistent with the subjects' profound intellectual disability. No Means-End (i.e., purposeful) behavior beyond Piagetian Sensorimotor Stage III could be elicited from the 6 girls. The relevance of this study for therapeutic intervention is discussed. PMID- 1624404 TI - Cognitive abilities of patients with Lesch-Nyhan disease. AB - Parents of 42 patients with Lesch-Nyhan disease completed a questionnaire systematizing caregiver observations of the subject's behavior during a wide variety of daily events. Responses were grouped in nine categories reflecting different aspects of cognitive skills. Only 1 boy appears to have any significant generalized cognitive impairment. The patients' memory for both recent and past events is excellent, their emotional life has a normal range of reactions and is appropriate; they have good concentration, are capable of abstract reasoning, have good self-awareness, and are highly social. However, they are behind in academic ability, with only 15% at grade level for math and reading. Implications for designing educational activities, parenting or caregiver strategies, and research methodology are discussed. PMID- 1624405 TI - Consistent stress profiles in mothers of children with autism. AB - The present study extends the area of research on stress in parents of autistic children. In this study we used the Questionnaire on Resources and Stress (Holroyd, 1987) to compare the stress profiles across mothers (a) who lived in different cultural and geographic environments; (b) who had children of different ages; and (c) who had children with different functioning levels. Results showed a characteristic profile that was highly consistent across each of these subgroups. Major differences from the normative data occurred on scales measuring stress associated with dependency and management, cognitive impairment, limits on family opportunity, and life-span care. Results suggest the importance of developing treatment programs aimed at reducing stress in specific areas in families with autistic children. PMID- 1624406 TI - Assessing resources and stress in parents of severely dysfunctional children through the Clarke modification of Holroyd's Questionnaire on Resources and Stress. AB - The Holroyd (1974) Questionnaire on Resources and Stress (QRS) although clinically useful may be too inclusive and not exclusively relevant to severely dysfunctional individuals. Hitherto, efforts at shortening and psychometrically validating the QRS have met with some success: the shorter forms however still target both mentally and physically handicapped children and are clinically not as useful as the original instrument. The 78-item Clarke modification of the QRS, mainly a subset of the original, was an attempt to remedy these problems. It was validated with mothers and fathers of autistic, mentally retarded, learning disabled, and asymptomatic children. Good internal consistency, split-half reliability, and coefficient of stability were obtained. Construct and concurrent validities were also acceptable. The questionnaire discriminated best between the two more severely affected groups and the controls. Group differences were found for 8 of its 9 scales and sex of parent differences were found for 3. The Clarke modification of the QRS is recommended for clinical use with parents of children with autism and mental retardation. PMID- 1624407 TI - Stress and family functioning in parents of girls with Rett syndrome. AB - Mothers and fathers of 29 girls with Rett syndrome provided data about their levels of parenting stress, marital adjustment, and family functioning. Their scores were compared to normative and clinical samples. The parents of girls with Rett syndrome reported more stress, lower marital satisfaction, and certain adaptations in family functioning compared to norms. However, most parents scored in the normal range on most measures and their scores were not related to SES. There was little relationship between specific characteristics of the daughter with Rett syndrome, such as her age and level of functioning, and her parents' scores on these measures. There were few significant differences between mothers' and fathers' scores. Results are discussed in terms of patterns of family adaptation and coping. Clinical implications are also discussed. PMID- 1624408 TI - Toilet training and behaviors of people with autism: parent views. AB - Individuals with autism often present with toileting problems, yet there is little information about the nature of these problems. This investigation surveyed 100 parents of people with autism of a mean age of 19.5 years. Results indicated that lower cognition and lower verbal levels were significantly correlated with age of accomplishment of bowel and urine training; some subjects were not trained at the time of the study. The average duration of urine training was 1.6 years, bowel training 2.1 years. On the average, training started more than 2 1/2 years before the average age of diagnosis of autism. Fifty-six percent of the sample had to be taught to self-initiate, 42% were taught to ask to use the toilet, and 49% were taught using a schedule. Reinforcement was used by 78% of the parents of males and by 100% of the parents of females. Punishment, primarily scolding was used by 37% of the parents. The most common problems reported were urinating in places other than the toilet, constipation, stuffing up toilets, continually flushing, or smearing feces. More fears related to toileting were noted for verbal subjects. PMID- 1624409 TI - Academic and environmental effects of small group arrangements in classrooms for students with autism and other developmental disabilities. AB - The use of small group instructional formats with children who have autism and developmental disabilities has received mixed results in the research literature (Reid & Favell, 1984). The purpose of the two studies reported herein was to address this controversy by comparing the performance of students in one-to-one instruction to those transitioned to small groups for a variety of teachers, students, settings, and under different training circumstances. In the first study, 41 students, ranging in age from 5 to 21 years old, from six classrooms, participated; and 25 students from six classrooms participated in the second study. Measures of environmental effects included academic gains via pre- and posttests, on-task and self-stimulatory behavior levels, correct responding, and frequencies of teacher behaviors during both one-to-one and small group formats. Results of both experiments indicated that students were able to successfully transition to small group formats across several curriculum areas including language, math, readiness, and shopping. Further, experienced teachers and administrators were able to train a second group of staff to use the small group procedures effectively. The successful application for this number of students and teachers within natural learning environments is unprecedented and provides important documentation for both the utility and practicality of small group instruction with students who have developmental disabilities. PMID- 1624410 TI - Plasma and urinary levels of biopterin, neopterin, and related pterins and plasma levels of folate in infantile autism. AB - Tetrahydrobiopterin is essential for brain cells to make monoamine neurotransmitters. It has been reported that the concentrations of tetrahydrobiopterin in plasma and urine are low in certain mental disorders and that oral supplements are beneficial. A group of Japanese investigators have been conducting clinical trials of the effect of administration of tetrahydrobiopterin to autistic children and reported that it is beneficial with no significant side effects. We, therefore, initiated a study to assess plasma and urinary levels of tetrahydrobiopterin in infantile autism to see if they are reduced. Besides tetrahydrobiopterin, we also determined plasma and urinary levels of neopterin and monapterin in these individuals in order to evaluate the status of dihydroneopterin triphosphate, a key biosynthetic precursor of tetrahydrobiopterin. Sixteen autistic children and 12 healthy controls were included in this study. Results indicated that the plasma and urinary levels of tetrahydrobiopterin are not statistically different between the two groups and, therefore, no simple explanation for the beneficial effects of administration of tetrahydrobiopterin on autistic children can be offered at the present time. In contrast, plasma and urinary levels of neopterin were depressed (.01 less than p less than .05) and plasma monapterin was also significantly depressed (p less than .01) in autistic subjects compared with controls. Levels of other pterins, including folate, were not statistically different between the two groups. The basis for this depression in neopterin and monapterin is unknown. It does not seem likely that this depression could be attributed to a difference in age or T lymphocyte/macrophage activity. However, further studies are needed to investigate these possibilities. PMID- 1624411 TI - Brief report: analysis of the internal consistency of three autism scales. PMID- 1624412 TI - Stress and immunological recognition in host-pathogen interactions. PMID- 1624413 TI - An operon of Bacillus subtilis motility genes transcribed by the sigma D form of RNA polymerase. AB - Two genes controlling motility functions in Bacillus subtilis were identified by DNA sequence analysis of a chromosomal fragment containing a strong promoter for sigma D RNA polymerase. Previous studies had shown that this sigma D-dependent promoter controls synthesis of a 1.6-kb transcript in vivo and in vitro. Sequence analysis revealed that the 1.6-kb transcript contains two open reading frames coding for protein sequences homologous to the Escherichia coli motA and motB gene products, respectively, and ends in a rho-independent termination site. Direct evidence linking these genes to motility functions in B. subtilis was obtained by precise localization by polymerase chain reaction of Tn917 transposon insertion mutations of Mot- strains, isolated by Zuberi et al. (A. R. Zuberi, C. Ying, H. M. Parker, and G. W. Ordal, J. Bacteriol. 172:6841-6848, 1990), to within this mot. operon. Replacement of each wild-type gene by in-frame deletion mutations yielded strains possessing paralyzed flagella and confirmed that both motA and motB are required for the motility of B. subtilis. These current findings support our earlier suggestions that sigma D in B. subtilis plays a central role in the control of gene expression for flagellar assembly, chemotaxis, and motility functions. Sigma F, the enteric homolog of sigma D, controls similar functions in E. coli and Salmonella typhimurium, and these factors appear to be representative of a family of factors implicated in flagellar synthesis in many bacterial species, which we propose to designate the sigma 28 family. PMID- 1624414 TI - The stable maintenance system pem of plasmid R100: degradation of PemI protein may allow PemK protein to inhibit cell growth. AB - We constructed plasmids carrying heat-inducible pemI and pemK genes, which were fused with the collagen-lacZ sequence in frame. The PemK-collagen-LacZ (PemK*) protein produced from the fusion gene upon heat induction inhibited the growth of cells and killed most of the cells in the absence of the PemI protein but did not do so in the presence of the PemI protein. This supports our previous assumption that the PemK protein inhibits cell division, leading to cell death, whereas the PemI protein suppresses the function of the PemK protein. We also constructed the plasmid carrying the heat-inducible pem operon which consists of the intact pemI gene and the pemK gene fused with collagen-lacZ. The simultaneously induced PemI and PemK* proteins did not inhibit the growth of cells. However, the temperature shift to 30 degrees C after induction of both proteins at 42 degrees C caused inhibition of cell growth and death of most cells. This suggests that the PemI protein is somehow inactivated upon the arrest of de novo synthesis of the PemI and PemK* proteins, allowing the PemK* protein to function. We observed that the PemI-collagen-LacZ (PemI*) protein was degraded faster than the PemK* protein, perhaps by the action of a protease(s). In fact, the lon mutation, which caused no apparent degradation of the PemI* protein, did not allow the PemK* protein to function, supporting the suggestion described above. Instability of the PemI protein would explain why the cells which have lost the pem+ plasmid are preferentially killed. PMID- 1624415 TI - Influence of attractants and repellents on methyl group turnover on methyl accepting chemotaxis proteins of Bacillus subtilis and role of CheW. AB - The ability of attractants and repellents to affect the turnover of methyl groups on the methyl-accepting chemotaxis proteins (MCPs) was examined for Bacillus subtilis. Attractants were found to cause an increase in the turnover of methyl groups esterified to the MCPs, while repellents caused a decrease. These reactions do not require CheW. However, a cheW null mutant exhibits enhanced turnover in unstimulated cells. Assuming that the turnover of methyl groups on the MCPs reflects a change in the activity of CheA, these results suggest that the activation of CheA via chemoeffector binding at the receptor does not require CheW. PMID- 1624416 TI - Characterization of a Bradyrhizobium japonicum ferrochelatase mutant and isolation of the hemH gene. AB - A Tn5-induced mutant of Bradyrhizobium japonicum, strain LORBF1, was isolated on the basis of the formation of fluorescent colonies, and stable derivatives were constructed in backgrounds of strains LO and I110. The stable mutant strains LOek4 and I110ek4 were strictly dependent upon the addition of exogenous hemin for growth in liquid culture and formed fluorescent colonies. The fluorescent compound was identified as protoporphyrin IX, the immediate precursor of protoheme. Cell extracts of strains LOek4 and I110ek4 were deficient in ferrochelatase activity, the enzyme which catalyzes the incorporation of ferrous iron into protoporphyrin IX to produce protoheme. Mutant strain I110ek4 could take up 55Fe from the growth medium, but, unlike the parent strain, no significant incorporation of radiolabel into heme was found. This observation shows that heme was not synthesized in mutant strain I110ek4 and that the heme found in those cells was derived from exogenous hemin in the growth medium. The putative protein encoded by the gene disrupted in strain LORBF1 and its derivatives was homologous to ferrochelatases from eukaryotic organisms. This homology, along with the described mutant phenotype, provides strong evidence that the disrupted gene is hemH, that which encodes ferrochelatase. Mutant strain I110ek4 incited nodules on soybean that did not fix nitrogen, contained few viable bacteria, and did not express leghemoglobin heme or apoprotein. The data show that B. japonicum ferrochelatase is essential for normal nodule development. PMID- 1624417 TI - Variation in antigenicity and molecular weight of Campylobacter coli VC167 flagellin in different genetic backgrounds. AB - Campylobacter coli VC167 has been shown to undergo a reversible flagellar antigenic variation between antigenic type 1 (T1) and antigenic type 2 (T2). VC167 contains two flagellin genes, and the products of both genes are incorporated into a complex flagellar filament in both antigenic types. Although there are only minor amino acid changes in the flagellins expressed by T1 and T2 cells, the two antigenic types of flagellins can be distinguished by differences in apparent M(r) on sodium dodecyl sulfate-polyacrylamide gels and by immunoreactivity with T1-specific (LAH1) or T2-specific (LAH2) antiserum. The isolation of stable variants of T1 and T2 has allowed for the transfer via natural transformation of the flagellin structural genes from the T1 background into the T2 background and from the T2 background into the T1 background. In addition, the flagellin genes from VC167 T1 and T2 have been transferred into strains of Campylobacter jejuni. The results indicate that the observed antigenic variations of VC167 flagellins are dependent on the host genetic background and independent of the primary amino acid sequence. These data provide evidence that posttranslational modifications are responsible for the antigenic variation seen in VC167 flagellins. PMID- 1624419 TI - Methylation of FrzCD, a methyl-accepting taxis protein of Myxococcus xanthus, is correlated with factors affecting cell behavior. AB - Myxococcus xanthus, a nonflagellated gliding bacterium, exhibits multicellular behavior during vegetative growth and fruiting body formation. The frizzy (frz) genes are required to control directed motility for these interactions. The frz genes encode proteins that are homologous to all of the major enteric chemotaxis proteins, with the exception of CheZ. In this study, we characterized FrzCD, a protein which is homologous to the methyl-accepting chemotaxis proteins from the enteric bacteria. FrzCD, unlike the other methyl-accepting chemotaxis proteins, was found to be localized primarily in the cytoplasmic fraction of cells. FrzCD migrates as a ladder of bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, reflecting heterogeneity due to methylation or demethylation and to deamidation. FrzCD was shown to be methylated in vivo when cells were exposed to yeast extract or Casitone and demethylated when starved in buffer. We used the methylation state of FrzCD as revealed by Western blot (immunoblot) analyses to search for stimuli that are recognized by the frz signal transduction system. Common amino acids, nucleotides, vitamins, and sugars were not recognized, but certain lipids and alcohols were recognized. For example, the saturated fatty acids capric acid and lauric acid stimulated FrzCD methylation, whereas a variety of other saturated fatty acids did not. Lauryl alcohol and lipoic acid also stimulated methylation, as did phospholipids containing lauric acid. In contrast, several short-chain alcohols, such as isoamyl alcohol, and some other solvents caused demethylation. The relatively high concentrations of the chemicals required for a response may indicate that these chemicals are not the relevant signals recognized by M. xanthus in nature. Isoamyl alcohol and isopropanol also had profound effects on the behavior of wild-type cells, causing them to reverse continuously. Cells of frzB, frzF, and frzG mutants also reversed continuously in the presence of isoamyl alcohol, whereas cells of frzA, frzCD, or frzE mutants did not. On the basis of the data presented, we propose a model for the frz signal transduction pathway in M. xanthus. PMID- 1624418 TI - Expression of recombinant proteins on the surface of the coagulase-negative bacterium Staphylococcus xylosus. AB - An expression system to allow targeting of heterologous proteins to the cell surface of Staphylococcus xylosus, a coagulase-negative gram-positive bacterium, is described. The expression of recombinant gene fragments, fused between gene fragments encoding the signal peptide and the cell surface-binding regions of staphylococcal protein A, targets the resulting fusion proteins to the outer bacterial cell surface via the membrane-anchoring region and the highly charged cell wall-spanning region of staphylococcal protein A. The expression system was used to secrete fusion proteins containing sequences from a malaria blood-stage antigen and a streptococcal albumin-binding receptor to the cell surface of S. xylosus. Analysis of the recombinant cells by immunogold staining and immunofluorescence revealed that both the receptor and the malaria peptide were properly processed and exposed on the surface of the host cells. However, only approximately 40 to 50% of the recombinant cells were strongly stained with antiserum reactive with the albumin-binding receptor, while approximately 10 to 15% of the cells were stained with antiserum reactive with the malaria peptide. The incomplete staining of some of the cells suggests steric effects that make the recombinant fusion proteins inaccessible to the reactive antibodies because of variable cell wall structures. However, the results demonstrate for the first time that recombinant techniques can be used to express heterologous receptors and immunogens on the surface of gram-positive cells. PMID- 1624420 TI - Use of hupS::lacZ gene fusion to study regulation of hydrogenase expression in Rhodobacter capsulatus: stimulation by H2. AB - The Escherichia coli beta-galactosidase enzyme was used as a reporter molecule for genetic fusions in Rhodobacter capsulatus. DNA fragments that were from the upstream region of the hydrogenase structural operon hupSLM and contained 5' hupS sequences were fused in frame to a promoterless lacZ gene, yielding fusion proteins comprising the putative signal sequence and the first 22 amino acids of the HupS protein joined to the eight amino acid of beta-galactosidase. We demonstrate the usefulness of the hupS::lacZ fusion in monitoring regulation of hydrogenase gene expression. The activities of plasmid-determined beta galactosidase and chromosome-encoded hydrogenase changed in parallel in response to various growth conditions (light or dark, aerobiosis or anaerobiosis, and presence or absence of ammonia or of H2), showing that changes in hydrogenase activity were due to changes in enzyme synthesis. Molecular hydrogen stimulated hydrogenase synthesis in dark, aerobic cultures and in illuminated, anaerobic cultures. Analysis of hupS::lacZ expression in various mutants indicated that neither the hydrogenase structural genes nor NifR4 (sigma 54) was essential for hydrogen regulation of hydrogenase synthesis. PMID- 1624421 TI - Mycoplasma pneumoniae cytadherence phase-variable protein HMW3 is a component of the attachment organelle. AB - The subcellular location of the phase-variable cytadherence-accessory protein HMW3 in Mycoplasma pneumoniae has been examined by biochemical and immunoelectron microscopic techniques. Analysis by Western blot (immunoblot) with HMW3-specific antiserum established the presence of this protein within the M. pneumoniae Triton X-100-insoluble fraction or triton shell. Immunogold labeling of Triton extracted mycoplasmas with affinity-purified antibodies localized HMW3 to the terminal knob on the rodlike extensions of the triton shell, a location that would correspond to the adherence organelle in whole mycoplasmas. Treatment of triton shells with KI resulted in the selective removal of the adherence accessory proteins HMW1 to HMW4. Analysis of these triton shells by transmission electron microscopy revealed dramatic ultrastructural changes in the filamentous network and core structure. Immunogold labeling of KI-extracted shells reflected the removal of HMW3 from the disrupted tip structure. An examination of ultrathin sections of wild-type cells by transmission electron microscopy following labeling with HMW3-specific antibodies provided further evidence for the nonrandom distribution of HMW3 and its localization to the terminal portion of filamentous cell extensions. Most colloidal gold molecules were associated with the cell interior, but limited peripheral labeling of the terminal region was also observed. Postfixation antibody labeling of whole cells suggested limited exposure of HMW3 on the mycoplasma surface at the tip structure. However, prefixation antibody labeling failed to indicate surface exposure, raising some uncertainty regarding the relationship of HMW3 with the mycoplasma membrane. PMID- 1624422 TI - Temperature sensing in Yersinia pestis: regulation of yopE transcription by lcrF. AB - In Escherichia coli, a yopE::lacZ fusion was found to be regulated by temperature in the presence of the cloned BamHI G fragment of Yersinia pestis plasmid pCD1, which contains the lcrF locus. Increasing the copy number of lcrF relative to that of the yopE reporter had a negligible effect on the induction ratio (26 versus 37 degrees C) but caused large reductions in the absolute levels of yopE transcription. We localized the lcrF gene by monitoring the induction phenotype of BamHI G deletion derivatives. Sequencing revealed an open reading frame capable of encoding a protein of 30.8 kDa. A protein product of this size was detected in a T7 expression system, and LcrF-dependent yopE-specific DNA binding activity was observed. As expected, LcrF exhibited 98% homology to VirF of Yersinia enterocolitica and significant homology to the carboxy termini of other members of the AraC family of transcriptional regulatory proteins. These proteins could be divided into two classes according to function: those regulating operons involved in catabolism of carbon and energy sources and those involved in regulating virulence genes. lcrF::lacZ transcriptional fusions were constructed and analyzed in Y. pestis and E. coli. The activity of the fusions was not affected by the native pCD1 virulence plasmid, an intact lcrF gene, or temperature. Thus, induction of lcrF transcription is not essential for temperature-dependent activation of yopE transcription. A portion of LcrF was found associated with the membrane fraction in E. coli; however, pulse-chase experiments indicated that this result is an artifact of fractionation. PMID- 1624423 TI - Identification of a protein-binding sequence involved in expression of an esterase gene from Streptomyces scabies. AB - Expression of an esterase gene from Streptomyces scabies is regulated by zinc in both Streptomyces scabies and Streptomyces lividans. A specific protein-binding site was identified on an esterase promoter fragment by using an S-30 extract from S. scabies. The location of the protein-binding site was determined by gel shift assays of promoter deletion fragments and by DNase I footprinting analysis. The protein-binding site maps from nucleotides -59 to -81 relative to the start of transcription. An esterase gene construct cloned and expressed in S. lividans was used to assess the importance of the protein-binding site. Deletion of the 23 bp protein-binding site resulted in a 10-fold decrease in esterase production when cells were grown in zinc-inducing conditions. The protein-binding site may represent a region involved in positive regulation of the S. scabies esterase gene. PMID- 1624424 TI - Disruption of the gene for Met-tRNA(fMet) formyltransferase severely impairs growth of Escherichia coli. AB - In bacteria, as well as in chloroplasts and mitochondria, the free amino group of the methionylated initiator tRNA(fMet) is specifically modified by the addition of a formyl group. The importance of this modification remains unclear. With the availability of pure Escherichia coli 10-formyltetrahydrofolate:L-methionyl tRNA(fMet) N-formyltransferase, the enzyme catalyzing Met-tRNA(fMet) formylation, the corresponding fmt gene and its flanking regions were cloned and sequenced. The chromosomal fmt gene was disrupted, and strains modified in their formylation activity were constructed. A depletion of the cellular formylation activity was accompanied by a decrease in the growth rate of the bacteria. At 37 degrees C, in a rich medium, the absence of a functional fmt gene reduced the growth rate to 0.28 doubling per h, from 2.3 for the control strain. At 42 degrees C, the studied fmt mutant strain did not grow further. PMID- 1624425 TI - TmrB protein, responsible for tunicamycin resistance of Bacillus subtilis, is a novel ATP-binding membrane protein. AB - tmrB is the gene responsible for tunicamycin resistance in Bacillus subtilis. It is predicted that an increase in tmrB gene expression makes B. subtilis tunicamycin resistant. To examine the tmrB gene product, we produced the tmrB gene product in Escherichia coli by using the tac promoter. TmrB protein was found not only in the cytoplasm fraction but also in the membrane fraction. Although TmrB protein is entirely hydrophilic and has no hydrophobic stretch of amino acids sufficient to span the membrane, its C-terminal 18 amino acids could form an amphiphilic alpha-helix. Breaking this potential alpha-helix by introducing proline residues or a stop codon into this region caused the release of this membrane-bound protein into the cytoplasmic fraction, indicating that the C-terminal 18 residues were essential for membrane binding. On the other hand, TmrB protein has an ATP-binding consensus sequence in the N-terminal region. We have tested whether this sequence actually has the ability to bind ATP by photoaffinity cross-linking with azido-[alpha-32P]ATP. Wild-type protein bound azido-ATP well, but mutants with substitutions in the consensus amino acids were unable to bind azido-ATP. These C-terminal or N-terminal mutant genes were unable to confer tunicamycin resistance on B. subtilis in a multicopy state. It is concluded that TmrB protein is a novel ATP-binding protein which is anchored to the membrane with its C-terminal amphiphilic alpha-helix. PMID- 1624426 TI - Effect of Salmonella typhimurium ferric uptake regulator (fur) mutations on iron- and pH-regulated protein synthesis. AB - Fur is an important regulatory protein known to function in the presence of iron as a repressor of iron-controlled genes. It was recently discovered that Fur is also essential to Salmonella typhimurium for mounting an adaptive acid tolerance response (J. W. Foster, J. Bacteriol 173:6896-6902, 1991). Because little is known about the effect of Fur on the physiology of this enteric pathogen, a systematic two-dimensional polyacrylamide gel electrophoresis (PAGE) analysis was conducted to identify proteins whose synthesis is linked to iron levels. Mutations in the fur locus were identified and used to classify which proteins are controlled by Fur. Thirty-six proteins were overtly affected by iron availability, most of which were clearly under the control of Fur. Although most of the Fur-dependent proteins were under negative control, a significant portion (15 of 34) appeared to be under a form of positive control. Nine of the positively controlled proteins required Fur and iron for expression. However, Fur lacking iron was also required for the induction of six gene products. Surprisingly, not all iron-regulated proteins were controlled by Fur and not all Fur-dependent proteins were obviously regulated by iron status. Because fur mutants fail to mount an effective acid tolerance response, we made a comparative two-dimensional PAGE analysis of 100 total acid- and iron-regulated gene products. Production of most of these proteins was regulated by only one of the two stresses, yet a clear subset of seven genes were influenced by both acid and iron and were also controlled by fur. These proteins were also members of the acid tolerance response modulon. Consistent with the fur effect on pH-regulated protein synthesis, fur mutants lacked the inducible pH homeostasis system associated with the acid tolerance response. The results provide further evidence that Fur has an extensive impact on gene expression and cellular physiology and suggest an explanation for the acid-sensitive nature of fur mutants. PMID- 1624427 TI - Klebsiella aerogenes urease gene cluster: sequence of ureD and demonstration that four accessory genes (ureD, ureE, ureF, and ureG) are involved in nickel metallocenter biosynthesis. AB - The region located immediately upstream from the Klebsiella aerogenes urease structural genes was sequenced and shown to possess an open reading frame capable of encoding a 29.8-kDa peptide. Deletions were generated in this gene, denoted ureD, and in each of the genes (ureE, ureF, and ureG) located immediately downstream of the three structural genes. Transformation of the mutated plasmids into Escherichia coli resulted in high levels of urease expression, but the enzyme was inactive (deletions in ureD, ureF, or ureG) or only partially active (deletions in ureE). Ureases were purified from the recombinant cells and shown to be identical to control enzyme when analyzed by gel filtration chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis; however, in every case the activity levels correlated to nickel contents as analyzed by atomic absorption analysis. UreD, UreE, UreF, and UreG peptides were tentatively identified by gel electrophoretic comparison of mutant and control cell extracts, by in vivo expression of separately cloned genes, or by in vitro transcription translation analyses; the assignments were confirmed for UreE and UreG by amino terminal sequencing. The latter peptides (apparent M(r)s, 23,900 and 28,500) were present at high levels comparable to those of the urease subunits, whereas the amounts of UreF (apparent M(r), 27,000) and UreD (apparent M(r), 29,300) were greatly reduced, perhaps because of the lack of good ribosome binding sites in the regions upstream of these open reading frames. These results demonstrate that all four accessory genes are necessary for the functional incorporation of the urease metallocenter. PMID- 1624428 TI - Increase of sensitivity to aminoglycoside antibiotics by polyamine-induced protein (oligopeptide-binding protein) in Escherichia coli. AB - The sensitivity of Escherichia coli to several aminoglycoside antibiotics was examined with E. coli DR112 transformed by the gene for polyamine-induced protein (oligopeptide-binding [OppA] protein) or polyamine transport proteins. The results clearly showed that sensitivity to aminoglycoside antibiotics (gentamicin, isepamicin, kanamycin, neomycin, paromomycin, and streptomycin) increased due to the highly expressed OppA protein. When the gene for OppA protein was deleted, sensitivity to aminoglycoside antibiotics was greatly decreased. It was also shown that isepamicin could bind to OppA protein with a binding affinity constant of 8.5 x 10(3) M-1 under the ionic conditions of 50 mM K+ and 1 mM Mg2+ at pH 7.5, and isepamicin uptake into cells was greatly stimulated by the OppA protein. These results, taken together, show that the OppA protein increases the uptake of aminoglycoside antibiotics. In addition, the OppA protein increased the transport of spermidine and an oligopeptide (Gly-Leu-Tyr). The uptake of isepamicin into cells was partially inhibited by spermidine, suggesting that the binding site for isepamicin overlaps that for spermidine on the OppA protein. Spermidine uptake activity by the OppA protein was less than 1% of that of the ordinary spermidine uptake system. Aminoglycoside antibiotics neither stimulated the synthesis of OppA protein nor increased spermidine uptake. PMID- 1624430 TI - Tyrosine phosphorylation of a membrane protein from Pseudomonas solanacearum. AB - We have investigated a tyrosine kinase activity from Pseudomonas solanacearum, an economically important plant pathogen. In vitro incubation of membrane fractions with [gamma-32P]ATP and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed an 85-kDa phosphoprotein. Phosphorylation of this protein on tyrosine residues was demonstrated by phosphoamino acid analysis of base hydrolysis products and by immunoanalysis of Western blots (immunoblots) with antiphosphotyrosine monoclonal antibody. In vitro incubation of membranes with ATP was not required for recognition by the antibody, indicating that the 85 kDa protein is phosphorylated in vivo. These results demonstrate that membranes from P. solanacearum exhibit a tyrosine kinase activity toward an endogenous membrane protein. This bacterium provides an opportunity to study the structure and function of a prokaryotic tyrosine kinase. PMID- 1624429 TI - Molecular and functional characterization of the Salmonella invasion gene invA: homology of InvA to members of a new protein family. AB - One of the earliest steps in the pathogenic cycle of the facultative intracellular pathogen Salmonella spp. is the invasion of the cells of the intestinal epithelium. We have previously identified a genetic locus, inv, that allows Salmonella spp. to enter cultured epithelial cells. invA is a member of this locus, and it is the first gene of an operon consisting of at least two additional invasion genes. We have constructed strains carrying nonpolar mutations in invA and examined the individual contribution of this gene to the invasion phenotype of Salmonella typhimurium. Nonpolar S. typhimurium invA mutants were deficient in invasion of cultured epithelial cells although they were fully capable of attaching to the same cells. In addition, unlike wild-type S. typhimurium, invA mutants did not alter the normal architecture of the microvilli of polarized epithelial cells nor did they cause any alterations in the distribution of actin microfilaments of infected cells. The invasion phenotype of invA mutants was readily rescued by wild-type S. typhimurium when cultured epithelial cells were simultaneously infected with both strains. On the contrary, in a similar experiment, the adherent Escherichia coli strain RDEC-1 was not internalized into cultured cells when coinfected with wild-type S. typhimurium. The invA locus was found to be located at about 59 min on the Salmonella chromosome, 7% linked to mutS. The nucleotide sequence of invA showed an open reading frame capable of encoding a polypeptide of 686 amino acids with eight possible membrane-spanning regions and a predicted molecular weight of 75,974. A protein of this size was visualized when invA was expressed in a bacteriophage T7 RNA polymerase-based expression system. The predicted sequence of InvA was found to be homologous to Caulobacter crescentus FlbF, Yersinia LcrD, Shigella flexneri VirH, and E. coli FlhA proteins. These proteins may form part of a family of proteins with a common function, quite possibly the translocation of specific proteins across the bacterial cell membrane. PMID- 1624431 TI - Role of the Bacillus subtilis gsiA gene in regulation of early sporulation gene expression. AB - The Bacillus subtilis gsiA operon was induced rapidly, but transiently, as cells entered the stationary phase in nutrient broth medium. A mutation at the gsiC locus caused sporulation to be defective and expression of gsiA to be elevated and prolonged. The sporulation defect in this strain was apparently due to persistent expression of gsiA, since a gsiA null mutation restored sporulation to wild-type levels. Detailed mapping experiments revealed that the gsiC82 mutation lies within the kinA gene, which encodes the histidine protein kinase member of a two-component regulatory system. Since mutations in this gene caused a substantial blockage in expression of spoIIA, spoIIG, and spoIID genes, it seems that accumulation of a product of the gsiA operon interferes with sporulation by blocking the completion of stage II. It apparently does so by inhibiting or counteracting the activity of KinA. PMID- 1624432 TI - Physical and functional maps of the luminescence gene cluster in an autoinducer deficient Vibrio fischeri strain isolated from a squid light organ. AB - Vibrio fischeri ES114 is an isolate representing the specific bacterial light organ symbiont of the squid Euprymna scolopes. An interesting feature of this strain of V. fischeri is that it is visibly luminous within the light organ of the squid host but is nonluminous when grown under standard laboratory conditions. Luminescence can be restored in laboratory culture, however, by the addition of autoinducer, a species-specific inducer of the V. fischeri luminescence (lux) genes. Most other isolates of V. fischeri produce autoinducer in sufficient quantities to induce luminescence in laboratory culture. We have cloned an 8.8-kb DNA fragment from V. fischeri ES114 that encodes all of the functions necessary for luminescence in Escherichia coli in the absence of exogenous autoinducer. This DNA contains both of the recognized V. fischeri lux regulatory genes, one of which (luxI) directs E. coli to synthesize autoinducer. The organization of the individual lux genes within this DNA fragment appears to be the same as that in the other strains of V. fischeri studied; the restriction map of the V. fischeri ES114 lux DNA has diverged substantially, however, from the largely conserved maps of V. fischeri MJ1 and ATCC 7744. Although E. coli containing the V. fischeri ES114 lux DNA synthesizes considerable amounts of autoinducer, V. fischeri ES114 synthesizes autoinducer only in small amounts, even when transcription of the lux genes, including luxI, is activated by the addition of exogenous autoinducer. Nonetheless, transconjugants of V. fischeri ES114 that contain multicopy plasmids bearing the ES114 lux genes synthesize sufficient autoinducer to induce luminescence. These results suggest that V. fischeri ES11r does not lack a functional luxl, nor is it deficient in the ability to synthesize metabolic precursors for autoinducer synthesis. PMID- 1624433 TI - Fusion-mediated transfer of plasmids into Spiroplasma floricola cells. AB - We have developed and characterized a system for the transfer of plasmids encapsulated in large unilamellar vesicles (LUV) into Spiroplasma floricola BNR1 cells. The approach is based on the ability of S. floricola-derived LUV to fuse with S. floricola cells. The fusion was continuously monitored by an assay for lipid mixing based on the dequenching of the fluorescent probe octadecylrhodamine B (R18) that was incorporated into LUV at self-quenching concentrations. The fusion was also evaluated by fluorescence-activated cell sorter measurements and by sucrose density gradient analysis. LUV-cell fusion occurred only in the presence of low concentrations (5%) of polyethylene glycol (polyethylene glycol 8000) and depended on temperature, the LUV/cell ratio, and divalent cations in the incubation medium. Throughout the fusion process, spiroplasma cells remained intact and viable. Under optimal fusion conditions, the plasmid pACYC, encapsulated in LUV by reversed-phase evaporation, was transferred into live S. floricola cells and expressed chloramphenicol acetyltransferase activity. The expression was transient with maximal chloramphenicol acetyltransferase activity observed after 6 h of incubation of the transfected cells. PMID- 1624434 TI - Evidence for the involvement of corrinoids and factor F430 in the reductive dechlorination of 1,2-dichloroethane by Methanosarcina barkeri. AB - Cobalamin and the native and diepimeric forms of factor F430 catalyzed the reductive dechlorination of 1,2-dichloroethane (1,2-DCA) to ethylene or chloroethane (CA) in a buffer with Ti(III) citrate as the electron donor. Ethylene was the major product in the cobalamin-catalyzed transformation, and the ratio of ethylene to CA formed was 25:1. Native F430 and 12,13-di-epi-F430 produced ethylene and CA in ratios of about 2:1 and 1:1, respectively. Cobalamin dechlorinated 1,2-DCA much faster than did factor F430. Dechlorination rates by all three catalysts showed a distinct pH dependence, correlated in a linear manner with the catalyst concentration and doubled with a temperature increase of 10 degrees C. Crude and boiled cell extracts of Methanosarcina barkeri also dechlorinated 1,2-DCA to ethylene and CA with Ti(III) citrate as the reductant. The catalytic components in boiled extracts were heat and oxygen stable and had low molecular masses. Fractionation of boiled extracts by a hydrophobic interaction column revealed that part of the dechlorinating components had a hydrophilic and part had a hydrophobic character. These chemical properties of the dechlorinating components and spectral analysis of boiled extracts indicated that corrinoids or factor F430 was responsible for the dechlorinations. The ratios of 3:1 to 7:1 of ethylene and CA formed by cell extracts suggested that both cofactors were concomitantly active. PMID- 1624435 TI - Methyl-coenzyme M reductase of Methanobacterium thermoautotrophicum delta H catalyzes the reductive dechlorination of 1,2-dichloroethane to ethylene and chloroethane. AB - Reductive dechlorination of 1,2-dichloroethane (1,2-DCA) to ethylene and chloroethane (CA) by crude cell extracts of Methanobacterium thermoautotrophicum delta H with H2 as the electron donor was stimulated by Mg-ATP. The heterodisulfide of coenzyme M (CoM) and 7-mercaptoheptanoylthreonine phosphate together with Mg-ATP partially inhibited ethylene production but stimulated CA production compared Mg-ATP alone. The pH optimum for the dechlorination was 6.8 (at 60 degrees C). Michaelis-Menten kinetics for initial product formation rates with different 1,2-DCA concentrations indicated the enzymatic character of the dechlorination. Apparent Kms for 1,2-DCA of 89 and 119 microM and Vmaxs of 34 and 20 pmol/min/mg of protein were estimated for ethylene and CA production, respectively. 3-Bromopropanesulfonate, a specific inhibitor for methyl-CoM reductase, completely inhibited dechlorination of 1,2-DCA. Purified methyl-CoM reductase, together with flavin adenine dinucleotide and a crude component A fraction which reduced the nickel of factor F430 in methyl-CoM reductase, converted 1,2-DCA to ethylene and CA with H2 as the electron donor. In this system, methyl-CoM reductase was also able to transform its own inhibitor 2 bromoethanesulfonate to ethylene. PMID- 1624436 TI - Cloning of a methanol-inducible moxF promoter and its analysis in moxB mutants of Methylobacterium extorquens AM1rif. AB - In Methylobacterium extorquens AM1, gene encoding methanol dehydrogenase polypeptides are transcriptionally regulated in response to C1 compounds, including methanol (M. E. Lidstrom and D. I. Stirling, Annu. Rev. Microbiol. 44:27-57, 1990). In order to study this regulation, a transcriptional fusion has been constructed between a beta-galactosidase reporter gene and a 1.55-kb XhoI SalI fragment of M. extorquens AM1rif DNA encoding the N terminus of the methanol dehydrogenase large subunit (moxF) and 1,289 bp of upstream DNA. The fusion exhibited orientation-specific promoter activity in M. extorquens AM1rif but was expressed constitutively when the transcriptional fusion was located on the plasmid. However, correct regulation was restored when the construction was inserted in the M. extorquens AM1rif chromosome. This DNA fragment was shown to contain both the moxFJGI promoter and the sequences necessary in cis for its transcriptional regulation by methanol. Transcription from this promoter was studied in the M. extorquens AM1rif moxB mutant strains UV4rif and UV25rif, which have a pleiotropic phenotype with regard to the components of methanol oxidation. In these mutants, beta-galactosidase activity from the fusion was reduced to a level equal to that of the vector background when the fusion was present in both plasmid and chromosomal locations. Since both constitutive and methanol-inducible promoter activities were lost in the mutants, moxB appears to be required for transcription of the genes encoding the methanol dehydrogenase polypeptides. PMID- 1624437 TI - Multiple mutant of Escherichia coli synthesizing virtually thymineless DNA during limited growth. AB - The dut gene of Escherichia coli encodes deoxyuridine triphosphatase, an enzyme that prevents the incorporation of dUTP into DNA and that is needed in the de novo biosynthesis of thymidylate. We produced a conditionally lethal dut(Ts) mutation and isolated a phenotypic revertant that had a mutation in an unknown gene tentatively designated dus (for dut suppressor). The dus mutation restored the ability of the dut mutant to grow at 42 degrees C without restoring its enzymatic activity or thymidylate independence. A strain was constructed bearing, in addition to these mutations, ones affecting the following genes and their corresponding products: ung, which produces uracil-DNA N-glycosylase, a repair enzyme that removes uracil from DNA; deoA, which produces thymidine (deoxyuridine) phosphorylase, which would degrade exogenous deoxyuridine; and thyA, which produces thymidylate synthase. When grown at 42 degrees C in minimal medium containing deoxyuridine, the multiple mutant displayed a 93 to 96% substitution of uracil for thymine in new DNA. Growth stopped after the cellular DNA had increased 1.6- to 1.9-fold and the cell mass had increased 1.7- to 2.7 fold, suggesting a general failure of macromolecular biosynthesis. DNA hybridization confirmed that the uracil-containing DNA was chromosomal and that new rounds of initiation must have occurred during its synthesis. PMID- 1624438 TI - Replication of prophage P1 is cell-cycle specific. AB - P1 prophage replication during the Escherichia coli division cycle has been analyzed by using the membrane-elution technique to produce cells labelled at different times during the division cycle and scintillation counting for quantitative analysis of radioactive prophage DNA. P1 prophage replicates during a restricted portion of the bacterial division cycle, like the minichromosome, but at a time during the division cycle different than the time at which the minichromosome replicates in the same cell. A high-copy mini-R6K plasmid present in the same cell replicates throughout the division cycle. Over a wide range of growth rates, the P1 prophage replicates approximately one-half generation after the minichromosome replicates. Thus, the mechanisms underlying P1 replication are similar to those for the F plasmid and the chromosome. Replication occurs when some property related to cell size or cell mass reaches a constant value per origin. PMID- 1624439 TI - Heat killing of bacterial spores analyzed by differential scanning calorimetry. AB - Thermograms of the exosporium-lacking dormant spores of Bacillus megaterium ATCC 33729, obtained by differential scanning calorimetry, showed three major irreversible endothermic transitions with peaks at 56, 100, and 114 degrees C and a major irreversible exothermic transition with a peak at 119 degrees C. The 114 degrees C transition was identified with coat proteins, and the 56 degrees C transition was identified with heat inactivation. Thermograms of the germinated spores and vegetative cells were much alike, including an endothermic transition attributable to DNA. The ascending part of the main endothermic 100 degrees C transition in the dormant-spore thermograms corresponded to a first-order reaction and was correlated with spore death; i.e., greater than 99.9% of the spores were killed when the transition peak was reached. The maximum death rate of the dormant spores during calorimetry, calculated from separately measured D and z values, occurred at temperatures above the 73 degrees C onset of thermal denaturation and was equivalent to the maximum inactivation rate calculated for the critical target. Most of the spore killing occurred before the release of most of the dipicolinic acid and other intraprotoplast materials. The exothermic 119 degrees C transition was a consequence of the endothermic 100 degrees C transition and probably represented the aggregation of intraprotoplast spore components. Taken together with prior evidence, the results suggest that a crucial protein is the rate-limiting primary target in the heat killing of dormant bacterial spores. PMID- 1624440 TI - Leuconostoc lactis beta-galactosidase is encoded by two overlapping genes. AB - A 16-kb BamHI fragment of the lactose plasmid pNZ63 from Leuconostoc lactis NZ6009 was cloned in Escherichia coli MC1061 by using pACYC184 and was found to express a functional beta-galactosidase. Deletion and complementation analysis showed that the coding region for beta-galactosidase was located on a 5.8-kb SalI BamHI fragment. Nucleotide sequence analysis demonstrated that this fragment contained two partially overlapping genes, lacL (1,878 bp) and lacM (963 bp), that could encode proteins with calculated sizes of 72,113 and 35,389 Da, respectively. The L. lactis beta-galactosidase was overproduced in E. coli by using a lambda pL expression system. Two new proteins with M(r)s of 75,000 and 36,000 appeared upon induction of PL. The N-terminal sequences of these proteins corresponded to those deduced from the lacL and lacM gene sequences. Mutation and deletion analysis showed that lacL expression is essential for LacM production and that both the lacL and lacM genes are required for the production of a functional beta-galactosidase in E. coli. The deduced amino acid sequences of the LacL and LacM proteins showed considerable identity with the sequences of the N- and C-terminal parts, respectively, of beta-galactosidases from other lactic acid bacteria or E. coli. DNA and protein sequence alignments suggest that the L. lactis lacL and lacM genes have been generated by an internal deletion in an ancestral beta-galactosidase gene. PMID- 1624441 TI - Thin aggregative fimbriae from diarrheagenic Escherichia coli. AB - Four strains of diarrheagenic Escherichia coli originally isolated from distinct geographic regions were found to produce unusual thin aggregative fimbriae requiring depolymerization in formic acid prior to analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunoelectron microscopy of native fimbriae and Western blot (immunoblot) analysis of the corresponding 18-kDa fimbrins showed that these E. coli fimbriae were serologically cross-reactive with SEF 17 (Salmonella enteritidis fimbriae with a fimbrin molecular mass of 17 kDa). The E. coli and S. enteritidis fimbrins had similar total amino acid compositions and highly conserved N-terminal amino acid sequences. These results indicate that E. coli and S. enteritidis produce biochemically related, aggregative fimbriae which constitute a new type of intergenerically distributed fimbriae for which we propose the descriptive name GVVPQ fimbriae on the basis of the conserved N-terminal amino acid sequence. PMID- 1624442 TI - Transformation of the gram-positive bacterium Clavibacter xyli subsp. cynodontis by electroporation with plasmids from the IncP incompatibility group. AB - We report the transformation of a gram-positive bacterium, Clavibacter xyli subsp. cynodontis, with several plasmids in the IncP incompatibility group from gram-negative bacteria. Our results suggest that IncP plasmids may be transferable to other gram-positive organisms. After optimizing electroporation parameters, we obtained a maximum of 2 x 10(5) transformants per microgram of DNA. The availability of a transformation system for this bacteria will facilitate its use in indirectly expressing beneficial traits in plants. PMID- 1624443 TI - Genetic and morphological characterization of an Escherichia coli chromosome segregation mutant. AB - The temperature-sensitive nucleoid segregation mutant of Escherichia coli, PAT32, formerly described as a parA mutant, has been shown to carry a mutation near 66 min on the genetic map. Fine mapping with phages from the collection of Kohara et al. is consistent with its being a parC allele. Observation by fluorescence microscopy revealed the formation, at a nonpermissive temperature, of filaments containing one or two large nucleoids and of normal-size anucleate cells. There was also a significant loss of viability. PMID- 1624444 TI - Nucleotide sequences of genes encoding penicillin-binding proteins from Streptococcus pneumoniae and Streptococcus oralis with high homology to Escherichia coli penicillin-binding proteins 1a and 1b. AB - The nucleotide sequence of a 3,378-bp DNA fragment of Streptococcus pneumoniae that included the structural gene for penicillin-binding protein (PBP) 1a (ponA), which encodes 719 amino acids, was determined. Homologous DNA fragments from an S. oralis strain were amplified with ponA-specific oligonucleotides. The 2,524-bp S. oralis sequence contained the coding region for the first 636 amino acids of a PBP. The coding sequence differed by 437 nucleotides (27%) and one additional triplet, resulting in 87 amino acid substitutions (14%), from S. pneumoniae PBP 1a. Both PBPs are highly homologous to bifunctional high-M(r) Escherichia coli PBPs 1a and 1b. PMID- 1624445 TI - Short, interspersed repetitive DNA sequences in prokaryotic genomes. PMID- 1624446 TI - Nucleotide sequences and genetic analysis of hydrogen oxidation (hox) genes in Azotobacter vinelandii. AB - Azotobacter vinelandii contains a heterodimeric, membrane-bound [NiFe]hydrogenase capable of catalyzing the reversible oxidation of H2. The beta and alpha subunits of the enzyme are encoded by the structural genes hoxK and hoxG, respectively, which appear to form part of an operon that contains at least one further potential gene (open reading frame 3 [ORF3]). In this study, determination of the nucleotide sequence of a region of 2,344 bp downstream of ORF3 revealed four additional closely spaced or overlapping ORFs. These ORFs, ORF4 through ORF7, potentially encode polypeptides with predicted masses of 22.8, 11.4, 16.3, and 31 kDa, respectively. Mutagenesis of the chromosome of A. vinelandii in the area sequenced was carried out by introduction of antibiotic resistance gene cassettes. Disruption of hoxK and hoxG by a kanamycin resistance gene abolished whole-cell hydrogenase activity coupled to O2 and led to loss of the hydrogenase alpha subunit. Insertional mutagenesis of ORF3 through ORF7 with a promoterless lacZ-Kmr cassette established that the region is transcriptionally active and involved in H2 oxidation. We propose to call ORF3 through ORF7 hoxZ, hoxM, hoxL, hoxO, and hoxQ, respectively. The predicted hox gene products resemble those encoded by genes from hydrogenase-related operons in other bacteria, including Escherichia coli and Alcaligenes eutrophus. PMID- 1624447 TI - Physical mapping of repetitive extragenic palindromic sequences in Escherichia coli and phylogenetic distribution among Escherichia coli strains and other enteric bacteria. AB - Repetitive extragenic palindromic (REP) sequences are highly conserved inverted repeat sequences originally discovered in Escherichia coli and Salmonella typhimurium. We have physically mapped these sequences in the E. coli genome by using Southern hybridization of an ordered phage bank of E. coli (Y. Kohara, K. Akiyama, and K. Isono, Cell 50:495-508, 1987) with generic REP probes derived from the REP consensus sequence. The set of REP probe-hybridizing clones was correlated with a set of clones expected to contain REP sequences on the basis of computer searches. We also show that a generic REP probe can be used in Southern hybridization to analyze genomic DNA digested with restriction enzymes to determine genetic relatedness among natural isolates of E. coli. A search for these sequences in other members of the family Enterobacteriaceae shows a consistent correlation between both the number of occurrences and the hybridization strength and genealogical relationship. PMID- 1624448 TI - Cloning of the HSP70 gene from Halobacterium marismortui: relatedness of archaebacterial HSP70 to its eubacterial homologs and a model for the evolution of the HSP70 gene. AB - Heat shock induces the synthesis of a set of proteins in Halobacterium marismortui whose molecular sizes correspond to the known major heat shock proteins. By using the polymerase chain reaction and degenerate oligonucleotide primers for conserved regions of the 70-kDa heat shock protein (HSP70) family, we have successfully cloned and sequenced a gene fragment containing the entire coding sequence for HSP70 from H. marismortui. HSP70 from H. marismortui shows between 44 and 47% amino acid identity with various eukaryotic HSP70s and between 51 and 58% identity with its eubacterial and archaebacterial homologs. On the basis of a comparison of all available HSP70 sequences, we have identified a number of unique sequence signatures in this protein family that provide a clear distinction between eukaryotic organisms and prokaryotic organisms (archaebacteria and eubacteria). The archaebacterial (viz., H. marismortui and Methanosarcina mazei) HSP70s have been found to contain all of the signature sequences characteristic of eubacteria (particularly the gram-positive bacteria), which suggests a close evolutionary relationship between these groups. In addition, detailed analyses of HSP70 sequences that we have carried out have revealed a number of additional novel features of the HSP70 protein family. These include (i) the presence of an insertion of about 25 to 27 amino acids in the N terminal quadrants of all known eukaryotic and prokaryotic HSP70s except those from archaebacteria and the gram-positive group of bacteria, (ii) significant sequence similarity in HSP70 regions comprising its first and second quadrants from organisms lacking the above insertion, (iii) highly significant similarity between a protein, MreB, of Escherichia coli and the N-terminal half of HSP70s, (iv) significant sequence similarity between the N-terminal quadrant of HSP70 (from gram-positive bacteria and archaebacteria) and the m-type thioredoxin of plant chloroplasts. To account for these and other observations, a model for the evolution of HSP70 proteins involving gene duplication is proposed. The model proposes that HSP70 from archaebacteria (H. marismortui and M. mazei) and the gram-positive group of bacteria constitutes the ancestral form of the protein and that all other HSP70s (viz., other eubacteria as well as eukaryotes) containing the insert have evolved from this ancient protein. PMID- 1624449 TI - Genetic analysis of absB, a Streptomyces coelicolor locus involved in global antibiotic regulation. AB - The filamentous soil bacterium Streptomyces coelicolor is known to produce four antibiotics which are genetically and structurally distinct. An extensive search for antibiotic regulatory mutants led to the discovery of absB mutants, which are antibiotic deficient but sporulation proficient. Genetic analysis of the absB mutants has resulted in definition of the absB locus at 5 o'clock on the genetic map. Multiple cloned copies of the actII-ORF4 gene, an activator of synthesis of the antibiotic actinorhodin, restore actinorhodin biosynthetic capability to the absB mutants. These results are interpreted to mean that the failure of absB mutants to produce antibiotics results from decreased expression of the antibiotic genes. The absB gene is proposed to be involved in global regulation of antibiotic synthesis. PMID- 1624450 TI - Mutational analysis of the precursor-specific region of Bacillus subtilis sigma E. AB - sigma E is a sporulation-specific sigma factor of Bacillus subtilis that is formed from an inactive precursor protein (pro-sigma E) by the removal of 27 to 29 amino acids from the pro-sigma E amino terminus. By using oligonucleotide directed mutagenesis, sequential deletions were constructed in the precursor specific region of sigE and analyzed for their effect on the gene product's activity, ability to accumulate, and susceptibility to conversion into mature sigma E. The results demonstrated that the first 17 residues of the pro sequence contribute to silencing the sigma-like activity of pro-sigma E and that the amino acids between positions 12 and 17 are also important for its conversion into sigma E. Deletions that remove 21 or more codons from sigE reduce sigma E activity in cells which carry it, presumably by affecting pro-sigma E stability. A 26-codon deletion results in a gene whose product is not detectable in B. subtilis by either reporter gene activity or Western blot (immunoblot) assay. The primary structure as well as the size of the pro region of sigma E contributes to the protein's stability. The placement of additional amino acids into the pro region reduces the cell's ability to accumulate pro-sigma E. Additional sigE mutations revealed that the amino acids normally found at the putative processing site(s) of pro-sigma E are not essential to the processing reaction; however, a Glu residue upstream of these sites (position 25) was found to be important for processing. These last results suggest that the pro-sigma E processing apparatus does not recognize the actual site within pro-sigma E at which cleavage occurs but rater sequence elements that are upstream of this site. PMID- 1624451 TI - Molecular characterization of the Entner-Doudoroff pathway in Escherichia coli: sequence analysis and localization of promoters for the edd-eda operon. AB - The nucleotide sequence of the entire Escherichia coli edd-eda region that encodes the enzymes of the Entner-Doudoroff pathway was determined. The edd structural gene begins 236 bases downstream of zwf. The eda structural gene begins 34 bases downstream of edd. The edd reading frame is 1,809 bases long and encodes the 602-amino-acid, 64,446-Da protein 6-phosphogluconate dehydratase. The deduced primary amino acid sequences of the E. coli and Zymomonas mobilis dehydratase enzymes are highly conserved. The eda reading frame is 642 bases long and encodes the 213-amino-acid, 22,283-Da protein 2-keto-3-deoxy-6 phosphogluconate aldolase. This enzyme had been previously purified and sequenced by others on the basis of its related enzyme activity, 2-keto-4-hydroxyglutarate aldolase. The data presented here provide proof that the two enzymes are identical. The primary amino acid sequences of the E. coli, Z. mobilis, and Pseudomonas putida aldolase enzymes are highly conserved. When E. coli is grown on gluconate, the edd and eda genes are cotranscribed. Four putative promoters within the edd-eda region were identified by transcript mapping and computer analysis. P1, located upstream of edd, appears to be the primary gluconate responsive promoter of the edd-eda operon, responsible for induction of the Entner-Doudoroff pathway, as mediated by the gntR product. High basal expression of eda is explained by constitutive transcription from P2, P3, and/or P4 but not P1. PMID- 1624452 TI - Regulation of transcription of the cell division gene ftsA during sporulation of Bacillus subtilis. AB - Three distinct 5' ends of ftsA mRNA were identified by S1 mapping and by primer extension analysis. These are thought to represent three transcription start sites. The transcripts from the downstream and upstream sites were detected throughout growth. The transcript from the middle site was not detected during exponential growth but was detected within 30 min of the start of sporulation, when it was the predominant transcript. Insertion of a cat cassette in the middle promoter, ftsAp2 (p2), did not affect vegetative growth but prevented postexponential symmetrical division and spore formation. Transcription from p2 was dependent on RNA polymerase containing sigma H, and promoter p2 resembled the consensus sigma H promoter. Transcription from p2 did not require expression of the spo0A, spo0B, spo0E, spo0F, or spo0K loci. Northern (RNA) blot analysis indicated that ftsA is cotranscribed with the adjacent ftsZ gene. Multiple promoters provide a mechanism by which essential vegetative genes can be subjected to sporulation control independent of control during vegetative growth. In the case of ftsA,Z, the promoters provide a mechanism to permit septum formation in conditions of nutrient depletion that might be expected to shut down the vegetative division machinery. PMID- 1624453 TI - Characterization of the genes encoding beta-ketoadipate: succinyl-coenzyme A transferase in Pseudomonas putida. AB - beta-Ketoadipate:succinyl-coenzyme A transferase (beta-ketoadipate:succinyl-CoA transferase) (EC 2.8.3.6) carries out the penultimate step in the conversion of benzoate and 4-hydroxybenzoate to tricarboxylic acid cycle intermediates in bacteria utilizing the beta-ketoadipate pathway. This report describes the characterization of a DNA fragment from Pseudomonas putida that encodes this enzyme. The fragment complemented mutants defective in the synthesis of the CoA transferase, and two proteins of sizes appropriate to encode the two nonidentical subunits of the enzyme were produced in Escherichia coli when the fragment was placed under the control of a phage T7 promoter. DNA sequence analysis revealed two open reading frames, designated pcaI and pcaJ, that were separated by 8 bp, suggesting that they may comprise an operon. A comparison of the deduced amino acid sequence of the P. putida CoA transferase genes with the sequences of two other bacterial CoA transferases and that of succinyl-CoA:3-ketoacid CoA transferase from pig heart suggests that the homodimeric structure of the mammalian enzyme may have resulted from a gene fusion of the bacterial alpha and beta subunit genes during evolution. Conserved functional groups important to the catalytic activity of CoA transferases were also identified. PMID- 1624455 TI - The catalytic domain of endoglucanase A from Clostridium cellulolyticum: effects of arginine 79 and histidine 122 mutations on catalysis. AB - Sequence analysis of the endoglucanase EGCCA of Clostridium cellulolyticum indicates the existence of two domains: a catalytic domain extending from residue 1 to residue 376 and a reiterated domain running from residue 390 to 450. A small deletion in the C terminal end of the catalytic domain inactivated the protein. From the analysis of the sequences of 26 endoglucanases belonging to family A, we focused on seven amino acids which were totally conserved in all the catalytic domains compared. The roles of two of these, Arg-79 and His-122, were studied and defined on the basis of the mutants obtained by introducing various substitutions. Our findings suggest that Arg-79 is involved in the structural organization of the protein; the His-122 residue seems to be more essential for catalysis. The role of His-123, which is conserved only in subfamily A4, was also investigated. PMID- 1624454 TI - Acetyl-coenzyme A synthesis from methyltetrahydrofolate, CO, and coenzyme A by enzymes purified from Clostridium thermoaceticum: attainment of in vivo rates and identification of rate-limiting steps. AB - Many anaerobic bacteria fix CO2 via the acetyl-coenzyme A (CoA) (Wood) pathway. Carbon monoxide dehydrogenase (CODH), a corrinoid/iron-sulfur protein (C/Fe-SP), methyltransferase (MeTr), and an electron transfer protein such as ferredoxin II play pivotal roles in the conversion of methyltetrahydrofolate (CH3-H4folate), CO, and CoA to acetyl-CoA. In the study reported here, our goals were (i) to optimize the method for determining the activity of the synthesis of acetyl-CoA, (ii) to evaluate how closely the rate of synthesis of acetyl-CoA by purified enzymes approaches the rate at which whole cells synthesize acetate, and (iii) to determine which steps limit the rate of acetyl-CoA synthesis. In this study, CODH, MeTr, C/Fe-SP, and ferredoxin were purified from Clostridium thermoaceticum to apparent homogeneity. We optimized conditions for studying the synthesis of acetyl-CoA and found that when the reaction is dependent upon MeTr, the rate is 5.3 mumol min-1 mg-1 of MeTr. This rate is approximately 10-fold higher than that reported previously and is as fast as that predicted on the basis of the rate of in vivo acetate synthesis. When the reaction is dependent upon CODH, the rate of acetyl-CoA synthesis is approximately 0.82 mumol min-1 mg-1, approximately 10 fold higher than that observed previously; however, it is still lower than the rate of in vivo acetate synthesis. It appears that at least two steps in the overall synthesis of acetyl-CoA from CH3-H4folate, CO, and CoA can be partially rate limiting. At optimal conditions of low pH (approximately 5.8) and low ionic strength, the rate-limiting step involves methylation of CODH by the methylated C/Fe-SP. At higher pH values and/or higher ionic strength, transfer of the methyl group of CH3-H4folate to the C/Fe-SP becomes rate limiting. PMID- 1624456 TI - Immunochemical differences among Methanosarcina mazei S-6 morphologic forms. AB - Methanosarcinae are the only archaeobacteria known to undergo major morphologic changes during growth involving unicellular and multicellular forms, and Methanosarcina mazei S-6 is the only strain for which three distinct forms, packets, single cells, and lamina, have so far been observed. It is reported that two pairs of these forms, either packets and single cells or single cells and lamina, grew and interconverted in medium with the same composition, Ca2+ and Mg2+ concentrations, and growth substrate, and that the two forms in each pair displayed distinctive differences revealed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting, the same growth medium substrate notwithstanding. PMID- 1624457 TI - A new mercury-penicillin V derivative as a probe for ultrastructural localization of penicillin-binding proteins in Escherichia coli. AB - The precise ultrastructural localization of penicillin-binding protein (PBP) antibiotic complexes in Escherichia coli JM101, JM101 (pBS96), and JM101(pPH116) was investigated by high-resolution electron microscopy. We used mercury penicillin V (Hg-pen V) as a heavy-metal-labeled, electron-dense probe for accurately localizing PBPs in situ in single bacterial cells grown to exponential growth phase. Biochemical data derived from susceptibility tests and bacteriolysis experiments revealed no significant differences between Hg-pen V and the parent compound, penicillin V, or between strains. Both antibiotics revealed differences in the binding affinities for PBPs of all strains. Deacylation rates for PBPs were slow despite the relatively low binding affinities of antibiotics. Cells bound most of the Hg-pen V added to cultures, and the antibiotic-PBP complex could readily be seen by electron microscopy of unstained whole mounts as distinct, randomly situated electron-dense particles. Fifty to 60% of the antibiotic was retained by cells during processing for conventional embedding so that thin sections could also be examined. These revealed similar electron-dense particles located predominantly on the plasma membrane and less frequently in the cytoplasm. Particles positioned on the plasma membranes were occasionally shown to protrude into the periplasmic space, thereby reflecting the high resolution of the Hg-pen V probe. Moreover, some particles were observed free in the periplasm, suggesting, for the first time, that a proportion of PBPs may not be restricted to the plasma membrane but may be tightly associated with the peptidoglycan for higher efficiency of peptidoglycan assembly. All controls were devoid of the electron-dense particles. The presence of electron-dense particles in cells of the wild-type JM101, demonstrated that our probe could identify PBPs in naturally occurring strains without inducing PBP overproduction. PMID- 1624458 TI - A positive regulatory gene, THI3, is required for thiamine metabolism in Saccharomyces cerevisiae. AB - We have isolated a thiamine auxotrophic mutant carrying a recessive mutation which lacks the positive regulatory gene, THI3, which differs in the regulation of thiamine transport from the THI2 (PHO6) gene described previously (Y. Kawasaki, K. Nosaka, Y. Kaneko, H. Nishimura, and A. Iwashima, J. Bacteriol. 172:6145-6147, 1990) for expression of thiamine metabolism in Saccharomyces cerevisiae. The mutant (thi3) had a markedly reduced thiamine transport system as well as reduced activity of thiamine-repressible acid phosphatase and of several enzymes for thiamine synthesis from 2-methyl-4-amino-5-hydroxymethylpyrimidine and 4-methyl-5-beta-hydroxyethylthiazole. These results suggest that thiamine metabolism in S. cerevisiae is subject to two positive regulatory genes, THI2 (PHO6) and THI3. We have also isolated a hybrid plasmid, pTTR1, containing a 6.2 kb DNA fragment from an S. cerevisiae genomic library which complements thiamine auxotrophy in the thi3 mutant. This gene was localized on a 3.0-kb ClaI-BglII fragment in the subclone pTTR5. Complementation of the activities for thiamine metabolism in the thi3 mutant transformed by some plasmids with the THI3 gene was also examined. PMID- 1624459 TI - Chlorosis induced by nutrient deprivation in Synechococcus sp. strain PCC 7942: not all bleaching is the same. AB - Cell coloration changes from normal blue-green to yellow or yellow-green when the cyanobacterium Synechococcus sp. strain PCC 7942 is deprived of an essential nutrient. We found that this bleaching process (chlorosis) in cells deprived of sulfur (S) was similar to that in cells deprived of nitrogen (N), but that cells deprived of phosphorus (P) bleached differently. Cells divided once after N deprivation, twice after S deprivation, and four times after P deprivation. Chlorophyll (Chl) accumulation stopped almost immediately upon N or S deprivation but continued for several hours after P deprivation. There was no net Chl degradation during N, S, or P deprivation, although cellular Chl content decreased because cell division continued after Chl accumulation ceased. Levels of the light-harvesting phycobiliproteins declined dramatically in a rapid response to N or S deprivation, reflecting an ordered breakdown of the phycobilisomes (PBS). In contrast, P-deprived cultures continued to accumulate PBS for several hours. Whole PBS were not extensively degraded in P-deprived cells, although the PBS contents of P-deprived cells declined because of continued cell division after PBS accumulation ceased. Levels of mRNAs encoding PBS polypeptides declined by 90 to 95% in N- or S-deprived cells and by 80 to 85% in P-deprived cells. These changes in both the synthesis and stability of PBS resulted in a 90% decline in the PC/Chl ratio of N- or S-deprived cells and a 40% decline in the PC/Chl ratio of P-deprived cells. Therefore, although bleaching appears to be a general response to nutrient deprivation, it is not the same under all nutrient-limited conditions and is probably composed of independently controlled subprocesses. PMID- 1624460 TI - Identification of the rph (RNase PH) gene of Bacillus subtilis: evidence for suppression of cold-sensitive mutations in Escherichia coli. AB - A shotgun cloning of Bacillus subtilis DNA into pBR322 yielded a 2-kb fragment that suppresses the cold-sensitive defect of the nusA10(Cs) Escherichia coli mutant. The responsible gene encodes an open reading frame that is greater than 50% identical at the amino acid level to the E. coli rph gene, which was formerly called orfE. This B. subtilis gene is located at 251 degrees adjacent to the gerM gene on the B. subtilis genetic map. It has been named rph because, like its E. coli analog, it encodes a phosphate-dependent exoribonuclease activity, RNase PH, that removes the 3' nucleotides from precursor tRNAs. The cloned B. subtilis rph gene also suppresses the cold-sensitive phenotype of other unrelated cold sensitive mutants of E. coli, but not the temperature-sensitive phenotype of three temperature-sensitive mutants, including the nusA11(Ts) mutant, that were tested. PMID- 1624461 TI - Structures of the rfaB, rfaI, rfaJ, and rfaS genes of Escherichia coli K-12 and their roles in assembly of the lipopolysaccharide core. AB - Analysis of the sequence of a 4.1-kb rfa region downstream from rfaP revealed four genes. The first of these encodes a basic protein of 36,730 Da and does not correspond to any known rfa gene. It has been designated rfaS. The second gene was identified as rfaB on the basis of its ability to complement a Salmonella typhimurium rfaB mutant and encodes a 42,060-Da protein. The third and fourth genes encode proteins of 39,423 and 36,046 Da which are strongly homologous to the RfaI and RfaJ proteins of S. typhimurium. Escherichia coli K-12 restriction fragments carrying these genes complement an S. typhimurium rfaI mutant and, at lower efficiency, an rfaJ mutant. The difference in complementation efficiency suggests that the rfaI and rfaJ genes of E. coli K-12 have sugar and acceptor specificities different from those of S. typhimurium, as predicted from the different lipopolysaccharide (LPS) core structures of the two organisms. Defined mutations affecting all four genes were constructed in vitro and crossed onto the chromosome. The phenotypes of these mutations suggest that extension of the core may require protein-protein interactions between the enzymes involved in core completion as well as the interaction of these enzymes with their specific acceptor molecules. Mutants blocked at rfaI or genes encoding earlier steps in core biosynthesis exhibited a single predominant LPS band on gels while mutants blocked at rfaJ or genes encoding later steps produced multiple strong bands, indicating that one of the processes generating core heterogeneity requires a functional rfaI gene. PMID- 1624462 TI - Comparison of lipopolysaccharide biosynthesis genes rfaK, rfaL, rfaY, and rfaZ of Escherichia coli K-12 and Salmonella typhimurium. AB - Analysis of the sequence of a 4.3-kb region downstream of rfaJ revealed four genes. The first two of these, which encode proteins of 27,441 and 32,890 Da, were identified as rfaY and rfaZ by homology of the derived protein sequences of their products to the products of similar genes of Salmonella typhimurium. The amino acid sequences of proteins RfaY and RfaZ showed, respectively, 70 and 72% identity. Genes 3 and 4 were identified as rfaK and rfaL on the basis of size and position, but the derived amino acid sequences of the products of these genes showed very little similarity (about 12% identity) between Escherichia coli K-12 and S. typhimurium. The next gene in the cluster, rfaC, encodes a product which also shows strong protein sequence homology between E. coli K-12 and S. typhimurium, as do the rfaF and rfaD genes which lie beyond it. Thus, the rfa gene cluster appears to consist of two blocks of genes which are conserved flanking a central region of two genes which are not conserved between these species. Although the RfaL protein sequence is not conserved, hydropathy plots of the two RfaL species are nearly identical and indicate that this is a typical integral membrane protein with 10 or more potential transmembrane domains. We noted the similarity of the structure of the rfa gene cluster to that of the rfb gene cluster, which has now been sequenced in several Salmonella serovars. The rfb cluster also contains a gene which lies within a central nonconserved region and encodes an integral membrane protein similar to protein RfaL. We speculate that protein RfaL may interact in a strain- or species-specific way with one or more Rfb proteins in the expression of surface O antigen. PMID- 1624463 TI - Characterization of the periplasmic flagellum proteins of Leptospira interrogans. AB - The structure and composition of periplasmic flagella (PF) from Leptospira interrogans serovar pomona type kennewicki were characterized. Electron microscopic observations showed that leptospiral PF were complex structures composed of an 11.3-nm-diameter core surrounded by two sheath layers with 21.5- and 42-nm diameters. Two-dimensional gel electrophoresis of isolated PF showed the presence of seven different proteins ranging in mass from 31.5 to 36 kDa. Rabbit polyclonal and mouse monoclonal antibodies against PF proteins were prepared and were used to localize specific proteins to portions of the PF structure by immunoelectron microscopy. A 34-kDa protein was associated with the 11.3-nm-diameter core filament, while a 36-kDa protein was associated with a PF sheath (21.5-nm-diameter filament). The amino termini of the 34- and 35.5-kDa proteins were homologous to PF core proteins of other spirochetes. The experimental data suggested that L. interrogans PF contains 2 proteins (34 and 35.5 kDa) in the PF core. PMID- 1624464 TI - Identification of a novel promoter in the replication control region of plasmid R6K. AB - A novel source of transcription has been detected in the replication region of plasmid R6K by using fusions involving the galK reporter gene. The -35 and -10 consensus RNA polymerase binding sites were identified in the region overlapping the binding sites for the R6K-encoded replication protein pi. Transcription from this promoter, designated P2, is repressed in vivo by pi-protein levels that are inhibitory for replication. Promoter-down mutations in P2 induced in vitro by bisulfite mutagenesis result in a reduced copy number of a beta-replicon but not of a gamma-replicon. Implications of the role of P2 in R6K replication are discussed. PMID- 1624465 TI - Ferric iron uptake in Erwinia chrysanthemi mediated by chrysobactin and related catechol-type compounds. AB - Erwinia chrysanthemi 3937 possesses a saturable, high-affinity transport system for the ferric complex of its native siderophore chrysobactin, [N-alpha-(2,3 dihydroxybenzoyl)-D-lysyl-L-serine]. Uptake of 55Fe-labeled chrysobactin was completely inhibited by respiratory poison or low temperature and was significantly reduced in rich medium. The kinetics of chrysobactin-mediated iron transport were determined to have apparent Km and Vmax values of about 30 nM and of 90 pmol/mg.min, respectively. Isomers of chrysobactin and analogs with progressively shorter side chains mediated ferric iron transport as efficiently as the native siderophore, which indicates that the chrysobactin receptor primarily recognizes the catechol-iron center. Free ligand in excess only moderately reduced the accumulation of 55Fe. Chrysobactin may therefore be regarded as a true siderophore for E. chrysanthemi. PMID- 1624466 TI - Molecular modelling of the three-dimensional structure and conformational flexibility of bacterial lipopolysaccharide. AB - Molecular modelling techniques have been applied to calculate the three dimensional architecture and the conformational flexibility of a complete bacterial S-form lipopolysaccharide (LPS) consisting of a hexaacyl lipid A identical to Escherichia coli lipid A, a complete Salmonella typhimurium core oligosaccharide portion, and four repeating units of the Salmonella serogroup B O specific chain. X-ray powder diffraction experiments on dried samples of LPS were carried out to obtain information on the dimensions of the various LPS partial structures. Up to the Ra-LPS structure, the calculated model dimensions were in good agreement with experimental data and were 2.4 nm for lipid A, 2.8 nm for Re LPS, 3.5 nm for Rd-LPS, and 4.4 nm for Ra-LPS. The maximum length of a stretched S-form LPS model bearing four repeating units was evaluated to be 9.6 nm; however, energetically favored LPS conformations showed the O-specific chain bent with respect to the Ra-LPS portion and significantly smaller dimensions (about 5.0 to 5.5 nm). According to the calculations, the Ra-LPS moiety has an approximately cylindrical shape and is conformationally well defined, in contrast to the O-specific chain, which was found to be the most flexible portion within the molecule. PMID- 1624467 TI - Candida albicans produces a cystatin-type cysteine proteinase inhibitor. AB - A cysteine proteinase inhibitor was found in culture media of Candida albicans. Purification to homogeneity of the inhibitor was performed by carboxymethyl papain-Sepharose affinity, DE-52 ion-exchange, and reverse-phase high performance liquid chromatographies. The purified inhibitor had an M(r) of 15 kDa and a pI of 4.9. It was more stable to heat and pH than most proteins. The N-terminal sequence of the first 30 residues demonstrated high similarity with that of human cystatin A. Thus, C. albicans cysteine proteinase inhibitor seems to belong to the cystatin superfamily. The inhibitor activity of the yeast cellular form was 4.0 times higher than that of the hyphal cellular form in 7-day culture media. It is suggested that the inhibitor has regulatory functions similar to those of its counterpart proteinases in the invasion of host cells. PMID- 1624468 TI - Elasticity of the sacculus of Escherichia coli. AB - Preparations of purified peptidoglycan of Escherichia coli (i.e., sacculi) were studied by low-angle laser light scattering. Control experiments and theoretical calculations based on the Rayleigh-Gans theory showed that the mean sacculus surface area could be accurately inferred from measurements with our apparatus by using computer routines developed previously. Large changes in the mean saccular surface area resulted from alterations in the stress caused by varying the net charge on the sacculi. The net charge was affected by altering the suspending medium pH, causing carboxyl and amino groups in the peptidoglycan to gain or lose protons, or by acetylation or succinylation of the amino groups. A preponderance of either plus or minus charges caused an expansion of the mean sacculus surface area. The largest increase in area probably represents the elastic limit of the peptidoglycan and was 300% above the area of isoionic sacculi. This degree of expansion is consistent with possible conformations of the intact peptidoglycan structure without necessitating rupture of the wall fabric. Our findings concerning saccular elasticity provide support for the surface stress theory. It provides a mechanism so that bacteria can grow and divide while maintaining turgor pressure, without the necessity of having and using proteins to do the mechanical work. PMID- 1624469 TI - Structure and regulation of the Yersinia pestis yscBCDEF operon. AB - We have investigated the physical and genetic structure and regulation of the Yersinia pestis yscBCDEF region, previously called lcrC. DNA sequence analysis showed that this region is homologous to the corresponding part of the ysc locus of Yersinia enterocolitica and suggested that the yscBCDEF cistrons belong to a single operon on the low-calcium response virulence plasmid pCD1. Promoter activity measurements of ysc subclones indicated that yscBCDEF constitutes a suboperon of the larger ysc region by revealing promoter activity in a clone containing the 3' end of yscD, intact yscE and yscF, and part of yscG. These experiments also revealed an additional weak promoter upstream of yscD. Northern (RNA) analysis with a yscD probe showed that operon transcription is thermally induced and downregulated in the presence of Ca2+. Primer extension of operon transcripts suggested that two promoters, a moderate-level constitutive one and a stronger, calcium-downregulated one, control full-length operon transcription at 37 degrees C. Primer extension provided additional support for the proposed designation of a yscBCDEF suboperon by identifying a 5' end within yscF, for which relative abundances in the presence and absence of Ca2+ revealed regulation that is distinct from that for transcripts initiating farther upstream. YscB and YscC were expressed in Escherichia coli by using a high-level transcription system. Attempts to express YscD were only partially successful, but they revealed interesting regulation at the translational level. PMID- 1624470 TI - Purification and partial characterization of a penicillin-binding protein from Mycobacterium smegmatis. AB - Penicillin-binding proteins (PBPs), although characterized from several organisms, have so far not been studied in mycobacteria. The present study is the first characterization of a PBP from Mycobacterium smegmatis. The PBP was purified by solubilization of the membranes with Triton X-100 and successive chromatography of the solubilized proteins on ampicillin-linked CH Sepharose 4B and DE-52. The purified PBP (M(r), 49,500) catalyzed a model transpeptidase reaction with the tripeptide acetyl2-L-Lys-D-Ala-D-Ala as the substrate and Gly Gly as the acceptor. The transpeptidase activity was inhibited by 50% at a benzylpenicillin concentration of 1.8 x 10(-7) M, which was similar to the concentration (1.1 x 10(-7) M) of benzylpenicillin required to saturate to 50% this PBP. Of several antibiotics tested, the concentration of antibiotic required to inhibit [35S]penicillin binding by 90% was found to be the lowest for cefoxitin and Sch 34343. PMID- 1624471 TI - Isolation, characterization, and physiological role of the pyruvate dehydrogenase complex and alpha-acetolactate synthase of Lactococcus lactis subsp. lactis bv. diacetylactis. AB - The pyruvate dehydrogenase complex of Lactococcus lactis subsp. lactis bv. diacetylactis has a specific activity of 6.6 U/mg and a Km of 1 mM for pyruvate. The specific activities of E2 and E3 in the complex are 30 and 0.36 U/mg, respectively. The complex is very sensitive to NADH inhibition and consists of four subunits: E1 alpha (44 kDa), E1 beta (35 kDa), E2 (73 kDa), and E3 (60 kDa). The L. lactis alpha-acetolactate synthase has a specific activity of 103 U/mg and a Km of 50 mM for pyruvate. Thiamine pyrophosphate (Km = 3.2 microM) and divalent cations are essential for activity. The native enzyme measures 172 kDa and consists of 62-kDa monomers. The role of both enzymes in product formation is discussed in view of NADH inhibition and competition for pyruvate. PMID- 1624472 TI - The replication initiator operon of promiscuous plasmid RK2 encodes a gene that complements an Escherichia coli mutant defective in single-stranded DNA-binding protein. AB - The amino acid sequence of the 13-kDa polypeptide (P116) encoded by the first gene of the trfA operon of IncP plasmid RK2 shows significant similarity to several known single-stranded DNA-binding proteins. We found that unregulated expression of this gene from its natural promoter (trfAp) or induced expression from a strong heterologous promoter (trcp) was sufficient to complement the temperature-sensitive growth phenotype of an Escherichia coli ssb-1 mutant. The RK2 ssb gene is the first example of a plasmid single-stranded DNA-binding protein-encoding gene that is coregulated with replication functions, indicating a possible role in plasmid replication. PMID- 1624473 TI - Interallelic complementation of dnaE(Ts) mutations. AB - Some Escherichia coli dnaE(Ts) alleles will functionally complement in trans. The complementation is not due to copy number and is compatible with dimeric interaction. PMID- 1624474 TI - Transfer of conjugal elements in oral black-pigmented Bacteroides (Prevotella) spp. involves DNA rearrangements. AB - Conjugal genetic elements in isolates of oral black-pigmented Bacteroides denticola (Prevotella denticola) and B. intermedius (P. intermedia) transfer tetracycline and penicillin resistance in the absence of plasmids. Transverse alternating-field electrophoresis of restricted chromosomal DNAs from transconjugants revealed arrangements indicating that transfer and insertion can involve more than one 60-kb copy of the elements and occurs at strongly preferred sites in the recipient chromosome. PMID- 1624475 TI - Anaerobic toluene oxidation to benzyl alcohol and benzaldehyde in a denitrifying Pseudomonas strain. AB - The denitrifying Pseudomonas strain K172 was grown with a generation time of 6 h to a cell density of 0.4 g (dry weight) per liter with toluene and nitrate as substrates. We found that anaerobic cell suspensions oxidize [14C]toluene first to [14C]benzyl alcohol and subsequently to [14C]benzaldehyde. This proves that the methyl group of toluene is oxidized without molecular oxygen to a hydroxymethyl group. PMID- 1624476 TI - Designing a user interface and computer screens for instruction: some considerations. AB - Computer-assisted instruction and interactive videodisc are being used more often in allied health sciences education and medical training. Because computer graphics screens can enhance both legibility and readability, an effective computer interface for instruction is basic to the design and development of both. This article discusses guidelines on legibility, which includes the use of graphics, type and text, contrast, and color. PMID- 1624477 TI - Computer-aided forensic facial reconstruction. AB - The reconstruction of facial features on the human skull for identification purposes has, in the past, utilized either two-dimensional drafting or three dimensional sculpting techniques. We have developed two- and three-dimensional computer-aided routines to minimize errors introduced by limits of artistic ability or by inconsistencies in the application of techniques. These routines allow generalized facial features to be manipulated to conform to the size and shape of a specific skull. Subtle alterations of the surface form, texture, and color, based on age, sex, and race, enhance the individuality of the generated facial form. PMID- 1624478 TI - The life and work of James F. Didusch. AB - This retrospective look at the life and work of James F. Didusch emphasizes the brilliance of his talent and the great value of his contribution to the medical sciences. Didusch was the first student of Max Brodel in the Department of Art As Applied to Medicine at Johns Hopkins University from 1911 to 1913. When the Carnegie Institute of Embryology was established at Johns Hopkins in 1913, Didusch was appointed as its illustrator. He remained the Carnegie Illustrator until his death in 1955. His rich treasury of artwork represents a lifelong pursuit and is a vital contribution to the field of medical illustration. PMID- 1624479 TI - Informed consent. PMID- 1624480 TI - The prevalence of seropositivity for human immunodeficiency virus in patients who have severe trauma. AB - Patients who have severe trauma have been reported to have a substantially increased rate of seropositivity for human immunodeficiency virus when compared with the general population. We reviewed the records of 1226 consecutive Code-3 trauma patients who were treated at our institution in San Antonio, Texas, between 1987 and 1989. All of the patients had serum drawn to be tested for the human immunodeficiency virus. In contrast with previously published studies, only 0.8 per cent of these trauma patients were seropositive. There was no appreciable difference between the prevalence of seropositivity in patients who sustained blunt trauma and those who sustained penetrating trauma. Exposure to human immunodeficiency virus for medical personnel who care for trauma patients remains a concern, but the risk may be lower than previously reported. PMID- 1624481 TI - Salvage and reinfusion of postoperative sanguineous wound drainage. A preliminary report. AB - Thirty-five patients who were to have posterior spinal arthrodesis, total hip arthroplasty, or total knee arthroplasty were entered into one of two groups: Group A, to receive unwashed, filtered sanguineous drainage from the wound, or Group B, to receive washed, filtered drainage. The purpose of this prospective study was to evaluate the safety, efficacy, and difficulty of reinfusion of washed compared with unwashed drainage that had been salvaged from the wound after an orthopaedic operation. The sixteen patients in Group A received a mean of 475 milliliters of unwashed drainage for each total knee arthroplasty, 427 milliliters for each total hip arthroplasty, and ten milliliters for the one posterior spinal arthrodesis. The complications included immediate hypotension (two patients), hyperthermia (one patient), and hypotension five hours after reinfusion (one patient). The latter patient died, four days after the operation, of a massive myocardial infarction. The nineteen patients in Group B received a mean of 193 milliliters of washed, filtered drainage for each total knee arthroplasty, 203 milliliters for each total hip arthroplasty, and 179 milliliters for each posterior spinal arthrodesis. Salvage and reinfusion of washed drainage from the wound caused no problems in these patients. PMID- 1624482 TI - Autologous transfusions for orthopaedic procedures at a children's hospital. AB - We conducted a critical review of the use of autologous transfusions in orthopaedics at a tertiary-care children's hospital. The cases of 198 children who deposited blood before an orthopaedic operation were analyzed. There were 175 children who were enrolled in the program of preoperative deposit of autologous blood who later needed transfusion of blood; 73 per cent of them received only autologous blood. Seventy patients also had intraoperative salvage. We were unable to document a proved benefit of intraoperative salvage of blood in this group of patients. Forty patients had some difficulty donating autologous blood preoperatively, but these problems were rarely serious. Major human errors occurred in thirteen patients and resulted in some patients receiving homologous transfusions while autologous blood components were still available. Fifty-five (40 per cent) of all of the transfusions were administered in clinical circumstances that failed to meet generally accepted criteria for transfusion, and fifty-four (38 per cent) of the postoperative transfusions also failed to meet these criteria. This was true of the homologous transfusions in the study as well. Although an autologous blood transfusion is a generally safe procedure, it is not without risk, and human errors can occur. In light of the potential complications, surgeons should adhere to the standard indications for transfusion when administering autologous blood. PMID- 1624483 TI - Anterior decompression and arthrodesis of the cervical spine: long-term motor improvement. Part I--Improvement in incomplete traumatic quadriparesis. AB - Between 1973 and 1983, fifty-eight patients who had an incomplete spinal-cord injury secondary to a fracture or dislocation of the cervical spine were managed by anterior cervical decompression and arthrodesis with iliac bone grafts. In all patients, myelography showed that displaced fragments of bone or disc were compressing the anterior aspect of the spinal cord. Anterior decompression was performed in an attempt to improve function in the upper and lower extremities. The average interval from the injury to the decompression was thirteen months (range, one month to nine years). Two patients died of cardiopulmonary disease within two months after the operation, and one patient died eighteen months after the operation. The remaining fifty-five patients were followed for an average of six years (range, two to seventeen years). Twenty-nine patients became functional ambulators after the operation. An additional six patients who could walk before the operation had improvement in the ability to walk. Noteworthy improvement in motor-root function in the upper extremities was seen in thirty-nine patients. Only nine patients had no signs of improvement of motor function. Improvement was less in the patients in whom operative decompression had been done more than twelve months after the injury. The patients who had an extension injury to a spondylotic spine were older, and fewer of them had improvement. No patient lost neurological function as a result of the operation. Anterior decompression and arthrodesis, even when performed late after the injury, can improve neurological function in both the upper and lower extremities in many patients who have incomplete quadriplegia due to a fracture or dislocation of the cervical spine. PMID- 1624484 TI - Anterior decompression and arthrodesis of the cervical spine: long-term motor improvement. Part II--Improvement in complete traumatic quadriplegia. AB - Fifty-one patients who had complete motor quadriplegia secondary to a fracture or dislocation of the cervical spine were managed by anterior cervical decompression and arthrodesis with iliac bone grafts between 1973 and 1983. In all patients, myelography demonstrated that displaced fragments of bone and disc were compressing the anterior aspect of the spinal cord. Decompression was performed in an attempt to gain further improvement of the motor-roots in the upper extremities and thereby to improve the ability of the patients to care for themselves. The average interval from the injury to the decompression was fifteen months (range, one month to eight years). Two patients died within two months after the operation, one had a respiratory arrest that resulted in brain damage one day after the operation, and two died from cardiovascular disease more than one year after the operation. The remaining forty-six patients were followed for an average of five years (range, two to thirteen years). Neurological improvement of at least two new functional motor-root levels was documented in seven patients and of one level, in eighteen. Increased motor strength by two or three grades was seen in six patients. Noteworthy motor improvement did not occur in the remaining twenty patients. The mean modified Barthel index (used to measure improvement in the ability to perform activities of daily living) increased from 17 to 33 (of a possible 100) points. Functionally important improvement of the caudad part of the cord occurred in only one patient. In one patient, neural injury, with loss of one motor-root level, occurred, with only partial improvement. At the latest follow-up examination, the result was poor in nine of eleven patients who had decompression eighteen months or more after the injury. Only two of these patients had any improvement in the Barthel index, and then of only 5 points each. The result also was poor in the five patients who were more than fifty-three years old; two had no improvement in the Barthel index, one improved by 5 points, and two died. PMID- 1624485 TI - Long-term evaluation of adolescents treated operatively for spondylolisthesis. A comparison of in situ arthrodesis only with in situ arthrodesis and reduction followed by immobilization in a cast. AB - The medical records and radiographs of forty-two adolescents (twenty-three male and nineteen female) who had had a posterolateral spinal arthrodesis for spondylolisthesis between 1950 and 1986 were reviewed to assess the long-term outcome of this form of treatment. The average age of the patients at the time of the operation was fourteen years (range, seven years and nine months to seventeen years and eleven months). The duration of the clinical and radiographic follow-up ranged from two years to twenty-seven years and seven months. All patients had an in situ arthrodesis of the involved vertebrae. Eighteen patients had no additional intervention, and twenty-four patients had reduction and application of a cast. Use of the cast led to a decrease in sagittal translation of more than 5 per cent in eighteen patients and a decrease in lumbosacral kyphosis (the slip angle) of more than 5 degrees in fourteen patients. Of the patients who did not have a cast, eight had an increase in sagittal translation of more than 5 per cent and ten had an increase in lumbosacral kyphosis of more than 5 degrees. There were no neurological problems at the time of the initial operation or after the reduction maneuver. At the most recent clinical follow-up examination, thirty eight patients had no complaints of low-back pain or any restriction of work related or recreational activities. Persistent low-back pain and pain in the lower extremities limited the activities of the remaining four patients, two of whom had another operation to alleviate these symptoms. PMID- 1624486 TI - Tendons, ligaments, and capsule of the rotator cuff. Gross and microscopic anatomy. AB - We investigated the structure of the myotendinous rotator cuff in thirty-two grossly intact cuffs from thirty fresh cadavera of subjects who had been seventeen to seventy-two years old at the time of death. We studied the gross anatomy of the capsule and ligaments of the cuff, as well as histological sections of the tendons of the subscapularis, supraspinatus, and infraspinatus muscles. The tendons were found to splay out and interdigitate to form a common, continuous insertion on the humerus. The biceps tendon was ensheathed by interwoven fibers derived from the subscapularis and supraspinatus tendons. The anterior margin and bursal surface of the supraspinatus tendon were enveloped by a thick sheet of fibrous tissue derived from the coracohumeral ligament. Fibers from the coracohumeral and glenohumeral ligaments were found concentrated in a plane between the capsule and the tendons of the cuff. Microscopically, in the region of the supraspinatus and infraspinatus tendons, the cuff was composed of five layers defined by the attachments and orientations of the fibrous elements in each of these layers. PMID- 1624487 TI - Excision of the radial head for congenital dislocation. AB - Eight elbows in six patients who had had excision of the radial head for congenital dislocation were evaluated an average of seven years postoperatively. The average age of the patients at the time of the excision was thirteen years (range, ten to 15.5 years). The dislocation was posterior in five elbows and posterolateral in three. The over-all increase in the arc of flexion-extension postoperatively compared with preoperatively was 11 degrees (p greater than 0.1): The over-all increase in the arc of rotation was significant at 53 degrees (p less than 0.002). Pain in the elbow had decreased compared with preoperatively, but all patients had minor pain in the wrist. The result was rated good in five elbows, fair in two, and poor in one. One patient had a repeat excision of the radial head after it re-formed, and this was the reason for the poor result. All patients were satisfied with the outcome of the operation. Contrary to previously published data, excision of the radial head for congenital dislocation resulted in an increased range of motion and a decrease in pain in the elbow in our patients. PMID- 1624488 TI - Release of the subscapularis for internal rotation contracture and pain after anterior repair for recurrent anterior dislocation of the shoulder. AB - Ten patients who had an internal rotation contracture and pain after an anterior repair for recurrent dislocation of the shoulder were treated by release of the subscapularis muscle. For six of the patients, radiographs demonstrated severe osteoarthrotic changes in the shoulder as well. The release was done an average of eleven years after the original procedure, which, for most patients, had been a Putti-Platt repair. After release of the subscapularis, each patient had less pain in the shoulder and an average increase of 27 degrees of external rotation. Release of the subscapularis can offer relief of pain and of functional limitations associated with the symptoms caused by an internal rotation contracture after an anterior repair of the shoulder. PMID- 1624489 TI - Frozen shoulder. A long-term follow-up. AB - Sixty-two patients (sixty-eight shoulders) who had been treated non-operatively for idiopathic frozen shoulder were evaluated subjectively and objectively at two years and two months to eleven years and nine months of follow-up (average, seven years). Thirty-one (50 per cent) of these patients still had either mild pain or stiffness of the shoulder, or both. The range of motion averaged 161 degrees of forward flexion, 157 degrees of forward elevation, 149 degrees of abduction, 65 degrees of external rotation, and internal rotation to the level of the fifth thoracic spinous process. Thirty-seven (60 per cent) of the sixty-two patients still demonstrated some restriction of motion as compared with study-generated control values (calculated as the average motion, in each plane, for the thirty seven unaffected shoulders of the patients who had unilateral disease). Ten patients had restriction of forward flexion; eight, of forward elevation; seventeen, of abduction; twenty-nine, of external rotation; and ten, of internal rotation. However, when the motion of each affected shoulder of thirty-seven patients who had unilateral involvement was compared with that of the unaffected contralateral shoulder, eleven (30 per cent) demonstrated some restriction. None of these patients had restriction of forward flexion; two had restriction of forward elevation; two, of abduction; seven, of external rotation; and seven, of internal rotation. The patients who had substantial restriction in three planes or more were thirteen times more likely to be men (p greater than 0.05). Marked restriction, when it was present, was most commonly in external rotation. Only seven patients (11 per cent) reported mild functional limitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1624490 TI - Compressive mechanical properties of human cancellous bone after gamma irradiation. AB - The effect of gamma irradiation on the mechanical properties of human bone was examined. Specimens of cancellous bone were cut from the proximal epiphyseal region of fresh-frozen tibiae and divided into control and irradiated groups according to anatomical region. The irradiated groups were exposed to 10,000, 31,000, 51,000, or 60,000 gray (1.0, 3.1, 5.1, or 6.0 megarad). The specimens were tested in compression to failure to determine failure stress, strain to failure, and elastic modulus. Failure stress and elastic modulus were found to be proportional to the square of the density and were normalized with respect to this property. Significant differences in normalized failure stress (p less than 0.001) and normalized elastic modulus (p = 0.003), when compared with the values for matched control specimens, were found only for the specimens that had been irradiated with 60,000 gray (6.0 megarad). PMID- 1624491 TI - Stabilization of acetabular fractures in elderly patients. AB - Eighteen patients who were sixty years or older and had an acute displaced fracture of the acetabulum were managed with open reduction and internal fixation. The average age of the patients was sixty-seven years (range, sixty to eighty-one years). Nine fractures were a result of a motor-vehicle accident, and nine occurred in a fall. Nine patients had multiple associated injuries, and most (sixteen patients) had other complex acetabular fractures. All of the patients had open reduction and internal fixation with either the ilioinguinal approach (thirteen patients) or the Kocher-Langenbeck approach (five patients). All patients were managed postoperatively with early mobilization and physical therapy. All fractures united, and only one patient had a partial loss of reduction. Four patients who had a concentric reduction had a gap of as much as three millimeters in the articular surface due to comminution of the fracture. The complications included two pulmonary emboli, which resolved with anticoagulation, and one undetected intra-articular fragment, which led to an additional operation. No infections or iatrogenic nerve injuries were noted. Seventeen of the eighteen patients were followed for at least two years (average, thirty-one months). These patients had an average Harris hip-score of 90 points postoperatively. The treatment was regarded as having failed in only one patient. Open reduction and internal fixation of selected displaced acetabular fractures in the elderly can yield good results and may obviate the need for early and often difficult total hip arthroplasty. PMID- 1624492 TI - Shrapnel wounds in children. AB - Nineteen children who had open fractures and skin wounds of at least two centimeters due to shrapnel were followed for one to five weeks after they had been injured. All of the patients were managed with debridement at twenty-four to forty-eight-hour intervals and were given cephalosporin antibiotics. Fourteen patients did well. The wounds in the three patients who had the least severe soft tissue injury were healing well at two weeks, and ten other patients were progressing to soft-tissue and osseous healing at five weeks. One patient had progressive but slower healing, and plastic reconstructive procedures would be advisable. Five patients had major problems. In one of these children, a wound continued to drain after six weeks. Three children had an amputation, and another child died due to a vascular injury. PMID- 1624493 TI - Massive femoral osteolysis and early disintegration of a polyethylene-bearing surface of a total knee replacement. A case report. PMID- 1624494 TI - Bilateral spontaneous lateral compartment syndrome in the legs of a patient who received a kidney and heart transplant. A case report. PMID- 1624495 TI - Unstable fractures of the pelvic ring. PMID- 1624496 TI - Degenerative lumbar spondylolisthesis with spinal stenosis. A prospective study comparing decompression with decompression and inter-transverse process arthrodesis. PMID- 1624497 TI - Magnetic resonance imaging of a rupture of the medial head of the gastrocnemius muscle. A case report. PMID- 1624498 TI - Total acromionectomy. A twenty-year review. PMID- 1624499 TI - Concomitant fractures of the scaphoid and the distal end of the radius: treatment by external fixation. A report of two cases. PMID- 1624500 TI - Fixation is fun. PMID- 1624501 TI - Prognostic factors in soft-tissue sarcoma. PMID- 1624502 TI - Ultrasound in clinical orthopaedics. PMID- 1624503 TI - Staging of soft-tissue sarcomas. Prognostic analysis of clinical and pathological features. AB - In a retrospective study of all 137 patients with soft-tissue sarcoma treated by surgery between 1972 and 1984, the clinical course was related to several host and tumour features, including the Surgical Staging System of Enneking, Spanier and Goodman (1980). Only patients free from metastasis with untreated primary lesions on admission were included. According to the Surgical Staging System, nine tumours were IA, 18 IB, 38 IIA and 72 IIB. Only 12 patients underwent amputation; 125 were treated by local surgery. The mean follow-up time was ten years (minimum five). For the whole series the probability of seven-year survival was 0.65; 42 patients (31%) died from tumour disease. All these had metastases and 24 also had local recurrence. The local recurrence rate was 36%. Multivariate analysis identified large tumour size and high histological grade as significant risk factors for metastatic disease and tumour-related death. Sex, age, tumour site, surgical margin and local recurrence showed no correlation with survival. The prognostic contribution of compartmentality was virtually nil. Histological grade combined with tumour size was found to give better prognostic information than that obtained by the Surgical Staging System. PMID- 1624504 TI - Selection bias in treatment of soft-tissue sarcoma. AB - We analysed 256 patients with primary soft-tissue sarcoma of the extremities diagnosed between 1970 and 1990 to see if tumour-related and host-related prognostic factors influenced both the selection of operation and the margin of clearance obtained at surgery. Amputation was more often performed in young patients, in those with distal tumours, and in those with deep-seated tumours. Inadequate surgical margins (those with a high risk of local recurrence) were more common in patients with deep-seated and large tumours than in patients with superficial and small tumours. These features of the tumour and the host, which have been shown to be prognostic for survival, also influenced the choice and performance of surgical procedures. PMID- 1624505 TI - Epidemiological, clinical and radiological aspects of osteopoikilosis. AB - Osteopoikilosis is a rare condition showing characteristic sclerotic lesions on radiographic examination, which are diagnostic for the trait. We report four patients presenting with various complaints and 49 members of their families who later were found to have osteopoikilosis. The mean age of all 53 was 27.5 years and the male:female ratio was 33:20. Most had lesions in the small tubular bones. We studied the epidemiological, clinical and radiological features of these patients and from the pedigrees conclude that the disease is inherited as an autosomal dominant. PMID- 1624506 TI - Thigh pain despite bone ingrowth into uncemented femoral stems. AB - Six porous-coated, uncemented femoral components were revised at a mean of 34.5 months for persistent thigh pain. At operation the stems were rigidly stable, difficult to extract, and showed good bony ingrowth. The four men and two women, with an average age of 59 years, all had thigh pain starting within the first year, progressive over time and unresponsive to conservative measures. These cases show that rigid fixation with good bony ingrowth does not guarantee the clinical success of a porous-coated uncemented femoral stem. PMID- 1624507 TI - Corrosion between the components of modular femoral hip prostheses. AB - We studied the tapered interface between the head and the neck of 139 modular femoral components of hip prostheses which had been removed for a variety of reasons. In 91 the same alloy had been used for the head and the stem; none of them showed evidence of corrosion. In contrast, there was definite corrosion in 25 of the 48 prostheses in which the stem was of titanium alloy and the head of cobalt-chrome. This corrosion was time-dependent: no specimens were corroded after less than nine months in the body, but all which had been in place for more than 40 months were damaged. We discuss the factors which may influence the rate of these changes and present evidence that they were due to galvanically accelerated crevice corrosion, which was undetected in previous laboratory testing of this type of prosthesis. PMID- 1624508 TI - Plasma viscosity and C-reactive protein after total hip and knee arthroplasty. AB - We studied the changes in plasma viscosity and C-reactive protein to establish normal values after total hip or knee arthroplasty. Viscosity decreased from 1.68 (+/- 0.017) to 1.57 (+/- 0.014) on the first postoperative day and thereafter rose to 1.60 (+/- 0.019), 1.75 (+/- 0.015), and 1.74 (+/- 0.011) on the third, seventh and fourteenth days respectively. Six to eight weeks after operation it had returned to pre-operative levels. A viscosity above the upper limit of the laboratory range, obtained more than two months after operation, may be considered as abnormal. The C-reactive protein level increased significantly on the first postoperative day and then decreased from a peak on the second day, attaining nearly normal levels at six to eight weeks after operation. It may be a more sensitive indicator of deep postoperative infection than plasma viscosity. PMID- 1624509 TI - The influence of footwear on the prevalence of flat foot. A survey of 2300 children. AB - We analysed static footprints of 2300 children between the ages of four and 13 years to establish the influence of footwear on the prevalence of flat foot. The incidence among children who used footwear was 8.6% compared with 2.8% in those who did not (p less than 0.001). Significant differences between the predominance in shod and unshod children were noted in all age groups, most marked in those with generalised ligament laxity. Flat foot was most common in children who wore closed-toe shoes, less common in those who wore sandals or slippers, and least in the unshod. Our findings suggest that shoe-wearing in early childhood is detrimental to the development of a normal longitudinal arch. PMID- 1624510 TI - The Oxford club-foot programme. AB - We treated 63 club feet in 44 patients by a defined programme of strapping from birth followed by one of two operations performed at six weeks, either a simple calcaneal tendon lengthening or a subtalar realignment, and reviewed them prospectively. The decision as to which operation to perform was taken at four weeks after radiographic measurement of the talocalcaneal angle. All but eight patients (ten feet) were followed for a mean of 8.7 years. The overall results after calcaneal tendon lengthening were satisfactory. The re-operation rate after subtalar realignment was high (39%) due to over or undercorrection of the deformity. PMID- 1624511 TI - Arthroscopic lavage and debridement for osteoarthritis of the knee. AB - We measured the effect of arthroscopic lavage and debridement of the osteoarthritic knee by comparing objective measurements of thigh muscle function before and after operation. There was some improvement in quadriceps isokinetic torque at six and 12 weeks after joint lavage but not after debridement. Neither method significantly relieved the patients' symptoms. PMID- 1624512 TI - Hip dysplasia in hereditary motor and sensory neuropathies. AB - Hip dysplasia complicating the hereditary motor and sensory neuropathies is not widely recognised. We describe four patients in whom the neuropathy affected the proximal muscles and we suggest that hereditary motor and sensory neuropathies may be responsible for the failure of the initial treatment of some neonatal dislocated hips. PMID- 1624513 TI - The changing epidemiology of osteomyelitis in children. AB - We reviewed 275 cases and calculated the prevalence of bacteriologically or radiologically confirmed acute haematogenous osteomyelitis in children under 13 resident in Greater Glasgow during 1970 to 1990. In the 20-year period there was a fall of over 50%, mainly involving cases of long-bone infection, and those due to Staphylococcus aureus. There was a reduced incidence of complications. The proportion of cases involving long bones decreased from 84% to 57%, and those of Staphylococcus aureus infection from 55% to 31%. These changes, in what is becoming a rare disease, need to be known to ensure early diagnosis and adequate treatment, particularly of subacute non-staphylococcal infection at unusual sites. PMID- 1624514 TI - Open fractures of the tibia in children. AB - We describe the results of treatment of open tibial fractures in 92 children; 22 fractures were Gustilo type I, 51 type II and 19 type III. All children received tetanus prophylaxis, systemic antibiotics for 48 hours and thorough debridement and irrigation of the wound. Fifty-one wounds with minimal soft-tissue injury were closed primarily. The other 41 were initially left open; of these, 18 small wounds were allowed to heal secondarily and 23 larger wounds required split skin grafts or soft-tissue local or microvascular free flaps. Stable fractures were reduced and immobilised in an above-knee plaster cast (71%) and external fixation (28%) was used for unstable fractures, extensive soft-tissue injury and multiple injuries. Short-term complications included compartment syndrome (4%), superficial infection (8%), deep infection (3%), delayed union (16%), nonunion (7.5%) and malunion (6.5%): these incidences are similar to those reported in adults. Selective primary closure of wounds did not increase the incidence of infection. External fixation was associated with a greater occurrence of delayed and nonunion than plaster immobilisation, but this technique was used most often for the more severe injuries. Late review, at 1.5 to 9.8 years, showed a high incidence of continuing morbidity including pain at the healed fracture site (50%), restriction of sporting activity (23%), joint stiffness (23%), cosmetic defects (23%) and minor leg-length discrepancies (64%). Open tibial fractures in children are associated with a high incidence of early and late complications, which are more frequent in children with Gustilo type III injuries. The Gustilo classification was a useful guide for predicting the outcome and planning treatment. PMID- 1624515 TI - Anterior column fractures of the acetabulum. AB - We retrospectively reviewed 20 patients at three to 19 years after displaced anterior fracture-dislocations of the hip. Eighteen of them were treated by traction, after ensuring that the femoral head was adequately reduced beneath the undisrupted part of the weight-bearing dome. Two required operation. Although none of the 18 conservatively treated fractures was reduced anatomically, the results were good in ten patients and excellent in the seven in whom the fracture did not involve the weight-bearing dome. We conclude that anterior column fractures have a favourable prognosis after conservative treatment. PMID- 1624516 TI - Locked nailing of humeral shaft fractures. Experience in Edinburgh over a two year period. AB - We report the results of locked Seidel nailing for 30 fractures of the humerus. There were frequent technical difficulties at operation especially with the locking mechanisms. Protrusion of the nail above the greater tuberosity occurred in 12 cases, usually due to inadequate locking, and resulted in shoulder pain and poor function. Poor shoulder function was also seen in five patients with no nail protrusion, presumably because of local rotator cuff damage during insertion. Our results suggest that considerable modifications are required to the nail, and possibly to its site of insertion, before its use can be advocated. PMID- 1624517 TI - Hyperextension-dislocation of the cervical spine. Ligament injuries demonstrated by magnetic resonance imaging. AB - We reviewed the magnetic resonance (MR) images of eight adults with acute hyperextension-dislocation of the cervical spine. The images were obtained to evaluate damage to the spinal cord. All eight patients had disruption of the anterior longitudinal ligament and of the annulus of the intervertebral disc, and separation of the posterior longitudinal ligament from the subjacent vertebra. Some, but not all, showed widening of the disc space, posterior bulging or herniation of the nucleus pulposus, and disruption of the ligamentum flavum. The MR demonstration of these ligament injuries, taken with the clinical and radiographic findings, establishes the mechanism of hyperextension-dislocation, confirms the diagnosis, and is relevant to management. PMID- 1624518 TI - Seat-belt injuries of the spine in young children. AB - Seat-belt fractures of the lumbar spine in adolescents and adults are well recognised but there are few reports of these injuries in young children. We reviewed all seat-belt injuries in skeletally immature patients (Risser 0), seen at a tertiary referral centre between 1974 and 1991. There were ten cases, eight girls and two boys, with an average age of 7.5 years (3 to 13). Four distinct patterns of injury were observed, most commonly at the L2 to L4 level. Paraplegia, which is thought to be uncommon, occurred in three of our ten cases. Four children had intra-abdominal injuries requiring laparotomy. There was a delay in diagnosis either of the spinal or of the intra-abdominal injury in five cases, although all had contusion of the abdominal wall, the 'seat-belt sign'. Treatment of the fractures was conservative, by bed rest and then hyperextension casts. The incidence of this potentially devastating injury can be reduced by the optimal use of restraints, but there is often a delay in diagnosis. Our classification system may aid in the early detection and evaluation of this injury. PMID- 1624519 TI - Neurofibromatosis of the cervical spine. A report of eight cases. AB - Eight patients with neurofibromatosis presented with symptoms of cervical spine involvement over a period of 17 years, five of them within the second decade of life. The symptoms included neurological deficit in five, a neck mass in four, and deformity in three; only two complained of pain. Osteolysis of vertebral bodies with kyphosis of more than 90 degrees was the most common radiological feature. Posterior fusion failed in the one patient in whom it was performed. Good results were achieved by anterior fusion, alone, or combined with posterior fusion. Surgical complications included one death in a patient with a malignant neurofibroma, and one case of transient neurological deterioration. PMID- 1624520 TI - Posterior fracture-dislocation of the shoulder. A superior subacromial approach for open reduction. AB - We describe 11 cases of posterior fracture-dislocation of the shoulder that required open reduction and fixation. Difficulties with access through anterior approaches led us to use the superior subacromial approach. This is an extension of the approach often used to expose the rotator cuff; the joint is opened by splitting the supraspinatus tendon 5 mm behind the cuff interval. The glenoid, proximal humerus and any fracture fragments can be seen from above, allowing reduction of the dislocation and osteosynthesis to be performed with minimal risk of damage to the humeral head and its blood supply. The proximity of the axillary nerve limits the exposure of the proximal humeral shaft. The superior subacromial approach is ideal for posterior dislocation with fracture of the articular segment, but is not suitable when there is a fracture of the proximal humeral shaft. PMID- 1624521 TI - The strength of surgical repairs of the rotator cuff. A biomechanical study on cadavers. AB - Using 26 cadaver shoulders, we produced a standard defect in the supraspinatus tendon and performed one of three types of repair. Their strength was found by testing in tension the force required to produce a gap of 3 mm, then 6 mm, and finally total disruption of the repair. The use of a polyethylene patch to spread the forces over the lateral bone surface and of extra sutures to grasp the tendon end raised by 2.6 times the load at which a 3 mm gap in the repair occurred and by 1.7 times the load to failure. PMID- 1624522 TI - Anatomy of the coraco-acromial arch. Relation to degeneration of the acromion. AB - We examined 200 scapular bones for signs of degenerative changes in the coraco acromial arch. The slope and length of the acromion and the height of the arch were found to be most closely associated with degenerative change. These anatomical features are not significantly altered by current techniques of subacromial decompression. PMID- 1624523 TI - Post-mortem description of slipped capital femoral epiphysis. AB - We found, in a museum collection of skeletons, nine adult hips with untreated slipped capital femoral epiphyses. All the specimens were from men, five black and two white. Their mean age at death was 44 years. Seven of the femora were retroverted beyond neutral and five had true varus deformities. Osteoarthritis was detected in eight of the hips and the most severe degeneration was seen in the most deformed hips. Radiography revealed that cysts which appeared to occupy the femoral head in fact lay in the metaphyseal bone of the femoral neck. PMID- 1624524 TI - Anterior cruciate ligament replacement with polyester fibre. A long-term study of tissue reactions and joint stability in sheep. AB - We excised the anterior cruciate ligament from the left stifle of 24 sheep and replaced it by a polyester fibre implant routed 'over the top' of the femoral condyle and fixed, using grommets and screws. All the joints were sound, and the animals moved normally until they were killed at six, 12 and 24 months after operation. We found that the implants were always covered by host tissue, which matured into bundles with a histological appearance similar to the natural ligament. The implants were joined to the bones by organised fibrous tissue and there was no anchorage loosening. There was no synovitis, but the operated joints showed progressive cartilage degeneration. The reconstructed joints became less stable immediately after operation, but regained normal stability as the neoligaments developed. The neoligaments lost strength with time, despite tissue ingrowth. The good functional, biomechanical, and histological results justify clinical trials of this type of implant. PMID- 1624525 TI - Magnetic resonance imaging of anterior cruciate ligament rupture. A new diagnostic sign. PMID- 1624526 TI - Fractures associated with patellar ligament grafts in cruciate ligament surgery. AB - We reviewed retrospectively 490 patellar ligament reconstructions for cruciate ligament injuries performed from 1980 to 1990. There were six cases of patellar splitting and three displaced patellar fractures in donor knees. The fissure fractures all occurred during the removal of the patellar bone block. The displaced fractures were sustained during early rehabilitation, and in two of the three patients, involved the normal contralateral knee. The major reasons for this complication were imprecise saw cuts, spreading osteotomies, and the use of a too large patellar bone block. When a trapezoidal bone block is used to self lock in the femoral tunnel, this should preferably be taken from the tibia. Special care is needed in rehabilitation when the graft has been taken from the contralateral knee. PMID- 1624527 TI - The ossific nuclei and the cartilage anlage of the talus and calcaneum. AB - We studied the ossific nuclei on radiographs of the feet of three stillborn infants, two with club feet, relating the size, position and alignment of each nucleus to the cartilaginous talus or calcaneum in which it lay. Anteroposterior projections of the nucleus of the talus show deformity of that bone as well as subtalar malalignment. Lateral projections of the calcaneal nucleus may underestimate the degree of hindfoot equinus. PMID- 1624528 TI - The innervation of vastus medialis obliquus. PMID- 1624529 TI - Cutting-out of the dynamic hip screw related to its position. PMID- 1624530 TI - Failure of growing endoprosthetic replacement of the humerus. PMID- 1624531 TI - Congenital elevation of the great toe. PMID- 1624532 TI - Aspiration and injection for meniscal cysts. PMID- 1624533 TI - Transgluteal fracture-dislocation of the hip. PMID- 1624534 TI - Pulsed electromagnetic fields. PMID- 1624535 TI - Rocking the foot. PMID- 1624536 TI - Porosis around prosthesis. PMID- 1624537 TI - Replacing the anterior cruciate ligament. PMID- 1624538 TI - Anterior cruciate reconstruction. PMID- 1624540 TI - Antiproliferative effects of free and liposome-encapsulated retinoic acid in a squamous carcinoma model: monolayer cells and multicellular tumor spheroids. AB - Antiproliferative effects of free retinoic acid (RA) and liposome-encapsulated RA (RAlp) were compared in a squamous carcinoma system using both monolayer cells and multicellular tumor spheroids (MTS), an in-vivo-like model with three dimensional histological structure. Initial studies examined the effect of lipid composition on the efficiency of RA encapsulation and on the subsequent toxicity of RAlp to red blood cells. In 5-day growth assays for monolayer cells, RA and RAlp (1 microM-0.1 nM) produced similar growth inhibition. In 6-day growth assays for MTS, RAlp was shown to have increased effectiveness. Liposomal uptake by the squamous carcinoma cells was examined by culturing monolayers and MTS with fluorescence-tagged liposomes and examining them under fluorescence microscopy between days 1 and 6. Phagocytosed liposomes were present, but their low levels suggested that other mechanisms of drug delivery such as adsorption, fusion or direct lipid transfer probably occurred for RAlp. Histological examination of MTS showed that RA and RAlp produced similar alterations. In this squamous carcinoma system, liposomes are effective in delivering retinoic acid and in producing biological effects in monolayer cells and within the three-dimensional structure of MTS. PMID- 1624539 TI - Fifty years of research on N-acetyl-2-aminofluorene, one of the most versatile compounds in experimental cancer research. AB - It is just about 50 years since the publication of the report on the toxicity and carcinogenicity of the potent carcinogen N-acetyl-2-aminofluorene (AAF). In 1940 very few reports on the carcinogenic activity of chemical compounds in experimental animals were available. The discovery of pure chemicals as carcinogens, such as AAF, azo dyes and benzo[a]pyrene, provided cancer researchers with a number of tools whereby the progressive changes involved in the induction of cancer could be studied in experimental systems. Contrary to the results with other carcinogens then known, AAF induced numerous types of tumors, but not at the site of application. This finding stimulated a great deal of interest in its use as an experimental carcinogen to study its metabolic fate and mechanism of action. During the following years an ever increasing number of reports appeared on the carcinogenicity of AAF in various species, on its metabolic fate, on the interaction of reactive metabolites with nucleic acids and proteins, and on its mutagenic activity. Particularly studies on the metabolism of AAF and the interaction with nucleic acids have contributed appreciably to our understanding of the mechanism of action of aromatic amines and also of other chemical carcinogens. It can be expected that AAF and its derivatives will continue to be used for specific applications in experimental cancer research. One of the most recent achievements is the preparation of site-specific AAF- and aminofluorene-modified DNA sequences for mutagenesis studies. PMID- 1624541 TI - The prostacyclin analogue cicaprost inhibits metastasis of tumours of R 3327 MAT Lu prostate carcinoma and SMT 2A mammary carcinoma. AB - Investigations on mechanisms of metastatic tumour spread revealed a role for compounds that inhibit tumour dissemination at the time of hematogenous dissemination. The platelet aggregation inhibitor prostacyclin and its stable analogues were shown to inhibit tumour-cell-induced platelet interaction as well as tumour cell adhesive mechanisms. This study concentrates on the effect of the stable prostacyclin analogue cicaprost: 5-[(E)-(1S,5S,6S,7R)-7-hydroxy-6-[(3S,4S) 3-hydroxy-4-methylnona-1 ,6- diinyl]-bicyclo[3,3,0]octan-3-ylidene]-3 oxapentanoic acid (Schering AG), as cyclodextrin clathrate, on spontaneous tumour metastases of two different carcinomas of the rat. In Cop rats bearing spontaneously metastasizing R 3327 MAT Lu prostate carcinomas, cicaprost (1.0 mg/kg p.o. daily) inhibited the number of lung metastases by about 80%, whereas the lower doses (0.1 and 0.5 mg/kg) exhibited borderline efficacy. In female Wistar-Furth rats bearing s.c. implanted SMT 2A mammary carcinomas, spontaneously metastasizing into regional lymph nodes and lungs, cicaprost (0.1, 0.5 and 1 mg/kg) p.o. daily exhibited a dose-dependent inhibition of the number of lung metastases. Five out of ten animals treated by 1 mg/kg were free of visible lung metastases. The weight of the axillary lymph node was significantly reduced by the 1 mg/kg dose of cicaprost, whereas lower doses had no effect on the weight of the lymph nodes. The growth of the primary tumour was not influenced by cicaprost in the R 3327 MAT Lu prostate carcinoma nor in the SMT 2A mammary carcinoma in the dose range tested. In conclusion, the stable prostacyclin analogue cicaprost exhibits a strong antimetastatic action in two metastasizing tumours of the rat and interferes with the steps not only of haematogenous, but also of lymphogenous metastasis. PMID- 1624542 TI - A new concentrated perfluorochemical emulsion and carbogen breathing as an adjuvant to treatment with antitumor alkylating agents. AB - Many anticancer drugs require oxygen to be cytotoxic or are selectively cytotoxic toward cells under oxygenated conditions. The effects of the dilute perfluorochemical emuolsion Fluosol with a wide variety of chemotherapeutic agents have been explored; however, it has not been possible to determine the optimal level of circulating perfluorochemical emulsion with anticancer drugs because the volume of Fluosol that may be administered is limiting. Using a new concentrated perfluorochemical emulsion, a wide range of perfluorochemical doses has been examined in combination with melphalan, cyclophosphamide and 1,3-bis(2 chloroethyl)-1-nitrosourea (BCNU) in the FSaIIC fibrosarcoma. When the perfluorochemical emulsion was administered by injection i.v. just prior to the injection of melphalan (10 mg/kg), cyclophosphamide (150 mg/kg) or BCNU (50 mg/kg), the greatest tumor growth delays were obtained with dosage levels between 4 g and 12 g of the perfluorochemical perfluorooctyl bromide/kg. With each drug the greatest tumor growth delays were obtained when the drug was prepared in the emulsion and the combination injected i.v. In each case, each dose of drug was followed by 6 h of breathing carbogen. The addition of the perfluorochemical emulsion/carbogen breathing to treatment with melphalan, BCNU or cyclophosphamide resulted in significant increases in the killing of tumor cells by these drugs without a concomitant increase in toxicity to bone marrow granulocyte/macrophage colony-forming units. In each case, preparing the drug in the perfluorochemical emulsion was most effective. These results indicate that clinical trial of this perfluorochemical emulsion/carbogen breathing in combination with cancer chemotherapy may be warranted. PMID- 1624543 TI - Spectrum of cell-cycle kinetics of alkylating agent adolezesin in gynecological cancer cell lines: correlation with drug-induced cytotoxicity. AB - Adolezesin is an analog of CC-1065. These compounds are among the most potent alkylating agents known to date. Currently Adolezesin is undergoing phase I clinical trials at several cancer centers in the USA. While the cytotoxic effects of Adolezesin have been addressed elsewhere, its effects on cell-cycle kinetics have not been reported. Flow cytometry was performed on five human gynecological cancer cell lines: AN3, AE7, BG1, HEC1A, and SKUT1B. Exposure to Adolezesin (U73975, Upjohn Co.) was done at near confluency at 0, 0.1, 0.2, 0.5, 1 and 5x, with x = 10 pg/ml as reference concentration, for 90 min. Cell samples were taken by trypsinization at 0, 24, 48, 72, 96, and 168 h for flow cytometry. The ATP chemosensitivity assays were performed on the above cell lines to establish dose/response curves. Flow-cytometric analyses revealed that there was a spectrum of cell-cycle perturbations, which included biphasic S and G2 blocks, reverse dose-dependent G2 blocks, and a sequential relationship of S and G2 blocks. This study demonstrated that the cell kinetic response to Adolezesin depended on several variables such as cell lines, drug sensitivity, concentrations, and sampling time. Because of this multivariable dependence and the lack of correlation with cytotoxicity, it would be difficult to use cell kinetic pertubations to predict chemotherapeutic response. PMID- 1624544 TI - Laser Doppler flux and tissue oxygenation of experimental tumours upon local hyperthermia and/or hyperglycaemia. AB - Laser Doppler fluxmetry and oxygen partial pressure (pO2) histography have been applied to investigate the acute effects of hyperthermia (HT) and/or hyperglycaemia (HG) on microcirculatory function and tissue oxygenation of subcutaneous rat tumours growing on the dorsum of the hind foot. The experiments were performed to test whether, and to what extent, the two adjunct treatment modalities applied alone or in combination can modify these therapeutically relevant parameters. Local HT was performed in a saline bath (44 degrees C) for 2 h; HG was induced by i.v. infusion of 40% glucose solution for 2.5 h (blood glucose levels: 35-40 mM during heating). Laser Doppler flux (LDF) in superficial tumour tissue regions was recorded over the entire treatment period; tumour pO2 distribution was evaluated immediately after termination of the treatment. HG alone reduced the average LDF signal to 18% of the baseline reading before treatment, but did not influence the tumour oxygenation status and the proportion of pO2 readings occurring in the radiobiologically hypoxic class (pO2 = O-2.5 mm Hg). This phenomenon is most probably due to the occurrence of the Crabtree effect (reduction of the O2 consumption rate when excess glucose is available within a malignant tumour). Hyperthermia alone reduced LDF to approximately the same extent, and led to a rise in the number of pO2 readings in the hypoxic range with only minor changes in the average pO2. The combined treatment (HT/HG) neither increased the fraction of "hypoxic" pO2 readings nor intensified the flow drop already present at the end of the tumour heating. It is thus concluded that under hyperglycaemia the oxygenation status of normothermic and heated tumours is maintained. It may therefore be hypothesized that hyperthermia in conjunction with hyperglycaemia might be a better "radiosensitizer" than hyperthermia alone. PMID- 1624546 TI - Central nervous system metastases in breast cancer. AB - Sixty-two breast cancer patients with central nervous system (CNS) metastases were reviewed. The CNS was the first site of metastatic involvement in 38 cases (61%). The median survival from the primary diagnosis was 3.0 years; from the diagnosis of the CNS metastasis, 6 months. The interval between primary diagnosis and CNS metastasis had a median value of 2.0 years; between the initial extra cranial metastasis and CNS metastasis this was 0.9 years. Prognostic factors for the appearance of CNS metastasis could not be identified. Subsequent to CNS metastasis appearing, the well-known prognostic factors for the survival time and the metastasis-free interval lose their importance. Brain metastases occur, above all, in patients aged between 50 and 55 years, very often in the first 2.5 years after the first distant metastasis and not later than 10 years from the primary diagnosis. PMID- 1624545 TI - Growth-stimulating phase of macrophage response to activation: the phenomenon and its implications for tumour growth and immunotherapy. AB - The dynamics of growth-stimulating and cytotoxic activity of mouse peritoneal macrophages (PMo) in response to in vivo and in vitro bacillus Calmette-Guerin (BCG) or bestatin treatment was studied. It was shown that BCG and bestatin induce cytotoxicity in PMo, and that after the cytotoxic response strong growth stimulating activity develops. PMo, rendered cytotoxic in vivo and afterwards cultivated in vitro, displayed the same switch from a cytotoxic to a growth stimulating phase. These results suggest that the growth-stimulating phase is the obligatory PMo response to biological response modifiers (BRM) at least to BCG and bestatin. The growth rate of tumours, transplanted into mice during the cytotoxic phase of the response to BCG, was suppressed, whereas tumours transplanted during the growth-stimulating phase were stimulated. It appears that the development of a growth-stimulating phase after the cytotoxic phase of response to activation by BRM could be one of the reasons for the limited effectiveness of immunotherapy based on the application of macrophage activators. PMID- 1624547 TI - Efficacy of cisplatin-based intraperitoneal chemotherapy as treatment of malignant peritoneal mesothelioma. AB - In an effort to examine the potential clinical utility of intraperitoneal (i.p.) therapy in the management of patients with malignant peritoneal mesothelioma, 19 individuals with this disease were treated with a cisplatin-based i.p. treatment regimen. All but 1 patient also received i.p. mitomycin. The treatment was generally well tolerated, although a maximum of only four or five courses of cisplatin (100 mg/m2 every 28 days) and mitomycin (5-10 mg/treatment given 7 days after each i.p. cisplatin administration) could be administered, the treatment principally being stopped because of disease progression or catheter failure. Of 15 patients with malignant ascites, 7 (47%) experienced control of fluid reaccumulation ranging from 2 months to 73+ months (median 8 months). While the median survival for the 19 patients was only 9 months, 4 (21%) patients survived for more than 3 years from the initiation of therapy, and 2 patients are currently alive and clinically disease-free more than 5 years from the start of the i.p. treatment program. We conclude that a subset of patients with peritoneal mesothelioma, principally those with small-volume residual disease following surgical tumor debulking, can benefit from a cisplatin-based i.p. treatment strategy with control of ascites and prolonged disease-free survival. PMID- 1624548 TI - Sarcoma of the pulmonary artery: report of two cases and a review of the literature. AB - Primary tumours of the pulmonary arteries are rare neoplasms seldom diagnosed during the patient's life time. We report on two cases of pulmonary artery sarcomas diagnosed during life time of the respective patients in intra-operative frozen sections by histopathological examination. Case 1 was of a 55-year-old man with a fibrosarcoma originating from the main pulmonary trunk. Case 2 was of a 43 year-old woman with a malignant fibrous histiocytoma originating from the right pulmonary artery. In both patients a radical tumour resection under cardiopulmonary bypass was attempted. Both patients, however, had a local tumour recurrence and died 18 months (patient 1) and 6 months (patient 2) after surgery. A review of pulmonary artery sarcomas is given. PMID- 1624549 TI - Clinical neuropsychology: 1960-1990. AB - Clinical neuropsychology has made significant progress during the past 30 years. Practice and research have expanded remarkably in scope and are more incisive and more highly focused. There has been an explosive development of test methods but clinical neuropsychologists have yet to take full advantage of them. An effort should be made to combine the strengths of the "fixed battery" and "flexible" approaches to assessment. Further advances in neuropsychological assessment will come about only to the degree that they are linked to evolving concepts of brain behavior relationships. Neuropsychologists now require a deeper understanding of basic neuroscience and cognitive psychology than was true in the past. Steps should be taken to insure that training to achieve that understanding is provided to the upcoming generation of neuropsychologists. PMID- 1624550 TI - Truth in labeling: are we really an international society? PMID- 1624551 TI - Detection of Babesia bovis carrier cattle by using polymerase chain reaction amplification of parasite DNA. AB - Carrier cattle infected with Babesia bovis are difficult to detect because of the low numbers of parasites that occur in peripheral blood. However, diagnosis of low-level infections with the parasite is important for evaluating the efficacies of vaccines and in transmission and epidemiological studies. We used the polymerase chain reaction (PCR) to amplify a portion of the apocytochrome b gene from the parasite and tested the ability of this method to detect carrier cattle. The target sequence is associated with a 7.4-kb DNA element in undigested B. bovis genomic DNA (as shown previously), and the amplified product was detected by Southern and dot blot hybridization. The assay was specific for B. bovis, since no amplification was detected with Babesia bigemina, Trypanosoma brucei, Anaplasma marginale, or leukocyte DNA. The target sequence was amplified in DNA from B. bovis Mexico, Texas, and Australia S and L strains, demonstrating the applicability of the method to strains from different geographic regions. The sensitivity of the method ranged from 1 to 10 infected erythrocytes extracted from 0.5 ml of blood. This sensitivity was about 1,000 times greater than that from the use of unamplified parasite DNA. By the PCR method, six B. bovis carrier cattle were detected 86% of the time (range, 66 to 100%) when they were tested 11 times, while with microscopic examination of thick blood smears, the same carrier cattle were detected only 36% of the time (range, 17 to 66%). The method provides a useful diagnostic tool for detecting B. bovis carrier cattle, and the sensitivity is significantly improved over that of current methods. The results also suggest that characteristics of the apocytchrome b gene may make this a valuable target DNA for PCR-based detection of other hemoparasites. PMID- 1624553 TI - Factors influencing the infectivity of Chlamydia pneumoniae elementary bodies on HL cells. AB - The influence of variations in the pH, NaCl concentration, temperature, and concentrations of calcium and magnesium ions on the survival of Chlamydia pneumoniae elementary bodies (EBs) outside the host cells was investigated. The survival was determined after various incubation periods by counting the inclusion-forming units after C. pneumoniae was cultured for 72 h on monolayers of HL cells. The normal physiological conditions were restored prior to infecting the HL cells with C. pneumoniae. Declines in the infectivities of C. pneumoniae EBs were observed at pH values of lower than 5 and higher than 8 or at NaCl concentrations of less than 80 mM. The viability of C. pneumoniae EBs in SPG medium decreased as the temperature and/or incubation period increased. Incubation temperatures of up to 20 degrees C and incubation periods of up to 48 h did not affect the viability of C. pneumoniae. One hundred percent of the C. pneumoniae EBs were infective after 1 h of incubation at 35 degrees C, whereas 90, 50, and 40% survived after incubations of 8, 24, and 48 h, respectively. The viability of C. pneumoniae was unaffected within the investigated range of Ca2+ and Mg2+ ion concentrations in the medium. The presence of 10% fetal calf serum in the incubation medium had a stabilizing effect on the viability of C. pneumoniae. This effect became more pronounced as the incubation period increased. PMID- 1624552 TI - Detection of antibodies inhibiting the ADP-ribosyltransferase activity of pertussis toxin in human serum. AB - Bordetella pertussis produces a protein virulence factor termed pertussis toxin. Many candidate pertussis vaccines are based on the rationale that an immune response that neutralizes the virulence activities of this toxin, which are thought to arise from its catalytic ADP-ribosyltransferase activity, would be beneficial. The report describes two methods that quantify the inhibition of this activity by human serum. One, termed a direct assay, involves an initial incubation of toxin with serum, a second incubation that activates the toxin, and a third incubation that measures the ADP-ribosyltransferase activity of the mixture. The other assay, termed a plate assay, involves immobilization of the toxin, exposure of the immobilized toxin to serum and washing of the plate, and then activation and assay of the toxin's ADP-ribosyltransferase activity. The plate assay may be more selective than the direct assay in terms of identifying antibodies that neutralize the toxin in vivo. Sera from controls, selected patients presenting with cough, and vaccinated infants were first analyzed by the direct assay. In contrast to sera from controls, sera from several of the patients and vaccinated infants strongly inhibited activity. Dose-response curves of inhibition were determined for samples from three vaccinated infants by both the direct and plate assays. One of the samples had a dose-response curve of a different shape and thus differed not only in titer but also in functional characteristics. A comparison of inhibition of ADP-ribosyltransferase activity and neutralization in a CHO cell assay indicated that there was incomplete agreement between the two assays. Taken together, these results indicate that measurement of inhibition of ADP-ribosyltransferase activity by human serum is practical and may be useful in the evaluation of responses to pertussis vaccines. PMID- 1624554 TI - Characterization of Pasteurella multocida from nasal cavities of piglets from farms with or without atrophic rhinitis. AB - A total of 137 strains of Pasteurella multocida isolated from the nasal tracts of pigs with and without clinical atrophic rhinitis (AR) were studied for their biochemical, antigenic, and toxigenic characteristics. There were no major biochemical differences among the P. multocida isolates. Capsular antigen types A and D were both present in the nasal cavities of the pigs with or without clinical AR. However, the prevalence of type D was higher on farms with pigs with AR. Types A and D with different somatic antigens could both be present in the same pig. There was no correlation between somatic types and/or capsular types with the clinical AR status of the pigs on the farm. Toxigenic isolates were found only in pigs which had a problem of clinical AR, and a great majority of these isolates belonged to type D. Since there was a high level of heterogeneity of the strains in the P. multocida population on a farm, several strains should be characterized before the diagnosis of AR could be excluded on the basis of the absence of isolation of rhinopathogenic P. multocida strains. PMID- 1624555 TI - Fluorogenic substrates for differentiation of gram-negative nonfermentative and oxidase-positive fermentative bacteria. AB - A total of 803 strains of gram-negative nonfermentative and oxidase-positive fermentative bacteria (38 taxa) were investigated for their ability to hydrolyze 53 different fluorogenic 4-methylumbelliferyl- and beta-naphthylamide-linked substrates within 6 h of incubation. The hydrolysis of 16 fluorogenic substrates showed high separation index values among the tested taxa, was reproducible, and showed good agreement with data in the literature. In combination with other biochemical tests (like carbon substrate utilization tests and classical biochemical tests), hydrolysis profiles can improve the differentiation of gram negative nonfermentative and oxidase-positive fermentative bacteria. PMID- 1624557 TI - Development and application of a new scheme of phages for typing and differentiating Salmonella strains from different sources. AB - A set of 25 phages for typing and differentiating Salmonella strains from different origins (food, water, and disease outbreaks) is described. All the strains were typeable by use of the phages, whereas by the serological method more than 5% of the strains could not be classified. By using the phage typing scheme, 75 phage types were established, and all the results were reproducible 1 and 6 months later. Some phages were serotype and serogroup specific, which may be useful in additional tests for the identification of strains of some Salmonella serotypes. In addition, the strains responsible for an outbreak possessed the same phage type, which implies the potential epidemiological use of these phages. PMID- 1624556 TI - High-performance liquid chromatography of corynomycolic acids as a tool in identification of Corynebacterium species and related organisms. AB - A high-performance liquid chromatography (HPLC) study of 307 strains of Corynebacterium species and related taxa revealed that strains classified as "Corynebacterium aquaticum"; "Corynebacterium asperum"; and Centers for Disease Control (CDC) groups 1, 2, A-3, A-4, A-5, B-1, B-3, E, F-2, and I-2 as well as some unidentified coryneforms do not contain any corynomycolic acids; therefore, they should not be included in the genus Corynebacterium. Such an HPLC method of identification permitted the correct assignment to the genus Rhodococcus of two unpigmented strains of coryneform bacteria whose mycolic acid profiles were comparable to those of Rhodococcus equi. Bacteria belonging to CDC groups ANF-1, ANF-3, F-1, G-1, G-2, and I-1, as well as some other Corynebacterium sp. strains, yielded corynomycolic acid HPLC patterns related to those of Corynebacterium species. Either similarities or differences were observed in the corynomycolic acid profiles of Corynebacterium species tested after culture on sheep blood agar and/or sheep blood agar supplemented with Tween 80, which demonstrated that identification at the species or group level is possible. However, Corynebacterium striatum and CDC group I-1 bacteria as well as CDC group G-1 and group G-2 bacteria had indistinguishable HPLC patterns. Conversely, some variations were observed within some species as Corynebacterium xerosis, C. striatum, and Corynebacterium minutissimum. The evaluation procedure of this HPLC method by mass spectrometry analysis of isolated eluted peaks revealed that analytical reverse-phase HPLC alone does not provide any structural information, since isomers with identical polarities coeluted as a single peak. Nevertheless, HPLC is a rapid and reliable method for identification of corynomycolic acid containing bacteria in the clinical microbiological laboratory. PMID- 1624558 TI - Method for detection of simian immunodeficiency virus neutralizing antibodies using a noncommercial antigen capture enzyme-linked immunosorbent assay. AB - A neutralization test (NT) using a noncommercial antigen capture enzyme-linked immunosorbent assay (ELISA) to detect simian immunodeficiency virus (SIV) growth in vitro was developed. The capture antibody was a mixture of purified macaque anti-SIV immunoglobulin G (IgG) and a monoclonal antibody to SIV p27. Captured antigens were detected by using purified macaque anti-SIV IgG conjugated to horseradish peroxidase. The NT reliably and sensitively detected differences when various amounts of SIV were used with positive and negative control macaque sera. Dilutions of sequential sera from a macaque (Macaca nemestrina) that had been experimentally infected with SIV were tested for neutralizing antibody with 300 50% tissue culture infective doses of SIV. In this macaque, neutralizing activity and anti-SIV IgG levels in serum (detected by ELISA) increased with time after SIV inoculation, and high IgG titers were required in serum before neutralization occurred in vitro. This simple NT, which detects the presence of SIV serum neutralizing antibodies at a low cost, will be useful for investigating the role of neutralizing antibodies in the SIV-infected macaque model for AIDS. PMID- 1624559 TI - Molecular epidemiology of trimethoprim-resistant Shigella boydii serotype 2 strains from Bulgaria. AB - In 1990 an increased number of strains of Shigella boydii serotype 2 were isolated from different regions of Bulgaria. Strains were reported as sporadic, although they showed identical phenotypic characteristics, including resistance to ampicillin, carbenicillin, streptomycin, sulfonamide, tetracycline, ticarcillin, and trimethoprim. The objective of this study was to determine the genetic relatedness of the strains and the mechanism of their antimicrobial resistance. Plasmid fingerprinting showed an identical pattern for 23 of 25 of the selected strains. All 25 strains tested transferred their resistances en bloc to an Escherichia coli recipient. Transconjugants contained a 112-kb R plasmid which carried all the resistance genes, including that conferring type I dihydrofolate reductase-mediated trimethoprim resistance (MIC greater than 2,000 micrograms/ml). Riboprobe analysis showed identical restriction length fragment polymorphisms, suggesting a highly conserved genome. All findings indicate that strains of S. boydii serotype 2 isolated in 1990 from different regions of Bulgaria were highly related genetically and can be considered representatives of a single bacterial clone. The presence of an R plasmid and selection pressure because of the usage of antimicrobial agents, particularly trimethoprim, have likely facilitated the spread of the clone throughout the country. PMID- 1624560 TI - Improved serological diagnosis of Toxoplasma gondii infection by detection of immunoglobulin A (IgA) and IgM antibodies against P30 by using the immunoblot technique. AB - Immunoglobulin M (IgM) and IgA antibodies against the major surface protein of Toxoplasma gondii were determined in a total of 195 human sera and five human cerebrospinal fluids by using a P30 membrane extract and the immunoblot technique. By using two different T. gondii strains (RH and BK) simultaneously as antigens, we were able to demonstrate diagnostically important strain-specific human antibody responses in 4.5% of the samples tested. A comparison of the immunoblot technique with an IgM immunocapture enzyme-linked immunosorbent assay demonstrated that the IgM and IgA immunoblot seems to be of advantage in the diagnosis of acute toxoplasmosis in certain groups of patients, especially in the diagnosis of cerebral toxoplasmosis in patients with AIDS. The immunoblot technique described is easy to perform and might be useful as an additional serological assay for routine diagnosis of T. gondii infections. PMID- 1624561 TI - Antibodies to Borrelia burgdorferi in rodents in the eastern and southern United States. AB - Serologic studies were conducted to determine whether white-footed mice (Peromyscus leucopus) and cotton mice (Peromyscus gossypinus) contained serum antibodies to Borrelia burgdorferi, the causative agent of Lyme borreliosis. Enzyme-linked immunosorbent assays detected antibodies to this spirochete in 35.7 and 27.3% of 56 P. leucopus and 535 P. gossypinus serum samples, respectively, collected in Connecticut, North Carolina, South Carolina, Georgia, Florida, Alabama, and Mississippi. Antibody titers ranged from 1:160 to greater than or equal to 1:40,960. On the basis of adsorption tests, the antibodies detected appeared to be specific to Borrelia spirochetes. Seropositive rodents in the eastern and southern United States, areas where human cases of Lyme borreliosis have been reported, indicate a widespread geographic distribution of B. burgdorferi or a closely related spirochete. PMID- 1624562 TI - Optimal survival of Helicobacter pylori under various transport conditions. AB - The ability of clinical isolates and type strains of Helicobacter pylori to survive in Stuart transport medium, isotonic saline solution, and urea-containing isotonic saline was evaluated. The influences of temperature (4, 10, 15, 20, and 30 degrees C) and holding time (6 to 48 h) and the effect of exposure to air on survival were also studied. The recovery rate of H. pylori was highest from Stuart transport medium in comparison with the recoveries from the other transport media tested. We found that at holding temperatures above 15 degrees C the organisms became noncultivable within 6 h or less, while they survived for 2 days or longer at 10 degrees C. The presence of urea at a concentration of 2% (wt/vol) in isotonic saline resulted in the loss of viability of the organisms tested. PMID- 1624563 TI - Detection of borreliacidal antibodies in hamsters by using flow cytometry. AB - Flow cytometry can be used to detect antibody that kills Borrelia burgdorferi. Borreliacidal activity was detected within 3 h of incubating B. burgdorferi with immune serum and complement. Right-angle light scatter and propidium iodide fluorescence were the cytometric parameters which correlated best with in vitro killing of B. burgdorferi. Flow cytometry is a rapid method for determining the presence of borreliacidal activity and may lead to a better serodiagnostic test for the detection of Lyme disease. PMID- 1624564 TI - Critical assessment of blood culture techniques: analysis of recovery of obligate and facultative anaerobes, strict aerobic bacteria, and fungi in aerobic and anaerobic blood culture bottles. AB - Recent reports have documented a decrease in anaerobic bacteremias and have questioned the need for routine anaerobic blood cultures. At the same time, we and others have noted an increase in fungal bloodstream infections. In this two part study, we first compared recoveries of obligate anaerobic bacteria with those of fungi over a 13-year period and then examined the recoveries of all bacteria and fungi in aerobic and anaerobic blood culture bottles during a 12 month period. During the 13-year period, the number of patients with anaerobic bacteremia remained relatively constant (average, 39 patients per year), while the incidence of fungemia steadily increased, from 12 patients in 1978 to 117 patients in 1990. Of the 1,090 anaerobic isolates, 55.1 and 90.2% were recovered in aerobic and anaerobic bottles, respectively, compared with 98.6 and 37.0% of the 2,582 fungi. During the 12-month period of evaluation, 2,980 bacteria and fungi were recovered in cultures collected from 1,555 patients. Overall, 21.1% more organisms were recovered in aerobic bottles than in anaerobic bottles, including significantly more Staphylococcus species; gram-positive aerobic bacilli; Escherichia, Enterobacter, Pseudomonas, Xanthomonas, and Acinetobacter species; miscellaneous gram-negative bacilli; and yeasts. Only anaerobic gram negative bacilli and non-spore-forming gram-positive bacilli were isolated more commonly in anaerobic bottles. These data support the concepts that bacteremia caused by obligate anaerobic bacteria is decreasing relative to sepsis caused by other bacteria and fungi and that the routine use of unvented anaerobic blood culture bottles reduces the recovery of common aerobic bloodstream pathogens. PMID- 1624565 TI - Tracking laboratory contamination by using a Bacillus cereus pseudoepidemic as an example. AB - From 1 March to 31 May 1990, Bacillus cereus was recovered from 24 of 5,534 (0.49%) blood cultures and 22 of 1,088 (2.02%) other body fluid cultures. The rarity of this organism as a pathogen and comparison with previous baseline rates led to the conclusion that it was a pseudoepidemic involving some form of culture contamination. Generalized precautions taken without specific knowledge of the contaminant source reduced the recovery rate of the organism. Recovery rates for the organism returned to normal baseline prevalence after environmental cultures and epidemiological analysis led to the sterilization of a contaminated water bath used for boiling thioglycollate media. The problems encountered in this investigation are examined, and a systematic approach to clinical laboratory epidemiology is outlined. PMID- 1624566 TI - Characterization of isolates of Mycobacterium avium serotypes 4 and 8 from patients with AIDS by multilocus enzyme electrophoresis. AB - Isolates of Mycobacterium avium serotypes 4 and 8 originating from patients with AIDS in New York City, Los Angeles, or San Francisco were further characterized by multilocus enzyme electrophoresis. Reference strains used to produce typing antisera were also examined. Thirty-one electrophoretic types (ETs) were found among 58 isolates of serotype 4, while 10 ETs were identified among 21 isolates of serotype 8. One major ET was found within each serotype, and these two ETs were closely related, separated by a genetic distance of only 0.05. Six ETs were found in more than one city. In four cases, isolates of serotypes 4 and 8 shared the same ET. Multilocus enzyme electrophoresis in combination with serotyping should be helpful in locating the specific infection sources of these commonly isolated opportunistic pathogens. PMID- 1624567 TI - Immunoglobulin G antibody avidity in patients with respiratory syncytial virus infection. AB - The titer and avidity of respiratory syncytial virus-specific antibodies were measured in 196 serum specimens from 93 children with an acute, laboratory confirmed respiratory syncytial virus infection. An enzyme immunoassay method based on the ability of urea to dissociate the bound antibodies with low avidity from the antigen was used. Three patterns of immune responses were observed. Children less than 6 months of age usually had low titers of antibodies with high avidity in their acute-phase serum samples. These antibodies were concluded to be of maternal origin, since their reaction pattern was similar to that of healthy adults. During the next few weeks, a slight increase in titers with a concurrent decrease in antibody avidity was observed. All children 6 to 24 months of age had low-avidity antibodies in their acute-phase serum samples, which matured to high avidity during the follow-up. On the contrary, about half of the children greater than 24 months of age had high-avidity antibodies already in the acute-phase serum samples. We conclude that the former children were experiencing primary infections with respiratory syncytial virus and the latter were experiencing reinfections. All adults with remote immunity had antibodies with high avidity. PMID- 1624568 TI - Enzyme immunoassay for detection of immunoglobulin G (IgG), IgM, and IgA antibodies against type 6B pneumococcal capsular polysaccharide and cell wall C polysaccharide in chinchilla serum. AB - Conjugation of the capsular polysaccharides of Streptococcus pneumoniae to protein carriers has introduced a new generation of pneumococcal vaccines which may be efficacious in preventing pneumococcal otitis media during infancy. The chinchilla model has been used extensively for studying the pathogenesis of pneumococcal otitis media and for testing the efficacy of early pneumococcal capsular polysaccharide (PCP) vaccines, but immunologic studies in the chinchilla have been limited by the lack of antibodies against specific immunoglobulin isotypes. By using affinity-purified rabbit immunoglobulin G (IgG) anti chinchilla IgG, IgM, and IgA, we developed a sensitive enzyme immunoassay that is highly specific for IgG, IgM, and IgA antibodies against type 6B PCP (anti-6B) and against C polysaccharide in chinchilla serum. Antibody titers increased in serum from five chinchillas immunized with a type 6B outer membrane protein complex vaccine. Increases of anti-6B IgG and IgM antibody titers were more striking than increases of anti-6B IgA or anti-C polysaccharide IgG, IgM, or IgA titers were. PMID- 1624569 TI - Rapid diagnosis of respiratory viral infections by using a shell vial assay and monoclonal antibody pool. AB - We compared the detection of seven respiratory viruses by using a commercially available monoclonal antibody pool in a 2-day shell vial assay with that by using standard cell culture with respiratory syncytial virus (RSV) enzyme-linked immunosorbent assay (ELISA)-negative nasal secretions from hospitalized children. We found 179 respiratory virus isolates by either method in 675 specimens. Overall, the shell vial assay detected 147 of 179 (79%) of the positives after 2 days; cell culture detected 148 of 179 (80%) after a mean incubation period of 7.6 days (range, 1 to 14 days). The sensitivity of the shell vial assay was 78% for RSV, 94% for influenza B virus, 83% for adenovirus, and 80% for parainfluenza viruses. The sensitivity of the cell culture was 70% for RSV, 79% for influenza B virus, 90% for adenovirus, and 89% for parainfluenza viruses. The 2-day shell vial assay allowed the detection of respiratory viruses in a clinically relevant time frame and rapidly detected RSV in specimens lacking RSV antigen by ELISA. PMID- 1624570 TI - Purification of sputum samples through sucrose improves detection of Mycobacterium tuberculosis by polymerase chain reaction. AB - A method is described for the routine preparation of sputum samples for detection of Mycobacterium tuberculosis by using polymerase chain reaction amplification. Liquefaction of sputum samples with NaOH and subsequent removal of inhibitors of the polymerase reaction with a 50% sucrose centrifugation step (5 min) in a desktop centrifuge allow direct amplification of a 123-bp repetitive region of the M. tuberculosis genome. We have evaluated the sensitivity and specificity of the sucrose method with 155 sputum specimens from patients suspected of having tuberculosis and from normal healthy volunteers. This method, in our opinion, is reproducible, sensitive, and reliable. Multiple samples can be handled simultaneously, and results can be obtained in one working day. PMID- 1624571 TI - Evaluation of the performance of commercial test kits for detection of Helicobacter pylori antibodies in serum. AB - We have compared the sensitivities, specificities, and predictive values of three commercial serological assays for the diagnosis of Helicobacter pylori infection. A qualitative latex method (Pyloriset; Orion Diagnostics), a semiquantitative enzyme-linked immunosorbent assay (ELISA) (GAP test IgG; Bio-Rad), and a quantiative ELISA (Helico-G; Porton Cambridge) were used in 109 untreated dyspeptic patients. The presence of H. pylori was established when the results of culture and/or histology of the gastric biopsies taken were positive. The prevalence of H. pylori infection was 62% (52% in 42 patients younger than 45 years of age and 69% in 67 patients older than 45 years of age). Sensitivities and specificities were 68 and 76% for Pyloriset, 89 and 77% for GAP test IgG, and 82 and 83% for Helico-G. The positive predictive values for all three tests were between 85 and 90%. The predictive values for the absence of disease with a negative result were 62, 82, and 74% for Pyloriset, the GAP test, and Helico-G, respectively. With Helico-G in the younger group (less than 45 years), sensitivity significantly lower (71 versus 87%) and a positive predictive value lower than those for the older group (greater than 45 years) were found. Either the sensitivities and specificities of commercial methods for the measurement of antibodies to H. pylori in serum must be improved or the relationship between the presence of antibodies and the presence of bacteria in the stomach at the time of investigation is too weak to allow the use of serological techniques instead of culture and histological investigation of gastric biopsy material. PMID- 1624572 TI - National hospital survey of anaerobic culture and susceptibility testing methods: results and recommendations for improvement. AB - The methods for performing anaerobic bacterial isolation and identification continue to change and improve. Anaerobic susceptibility testing has become controversial, and method-dependent variability has been noted. To assess the status of clinical anaerobic bacteriology in the United States, we surveyed, by means of a questionnaire, 120 hospitals, selected at random, with bed capacities of 200 to 1,000, and we received responses from 88 (73%). All hospitals performed cultures for anaerobes. The media and methods used for transport, initial processing, incubation, and identification varies between the different regions in the United States. Thirty percent of laboratories did not perform susceptibility studies, 16% used a reference laboratory, and 54% performed them in house. For half the laboratories, susceptibility testing was performed on isolates depending on the source; in this case, blood cultures were tested by 97% of the laboratories, serious infections were tested by 60%, sterile body sites were tested by 73%, pure cultures were tested by 47%, and tests were done by physician request by 39%. For laboratories doing testing, the broth disk method, no longer sanctioned by the National Committee for Clinical Laboratory Standards, was used most often (56%), followed by microdilution (33%), beta-lactamase testing (25%), macrotube dilution (2%), and agar dilution (2%). The antimicrobial agents tested were as follows: penicillin-ampicillin, 94%; clindamycin, 94%, metronidazole, 90%; chloramphenicol, 80%; cefoxitin, 76%; tetracyclines, 51%; and erythromycin, 45%. All other agents were tested by less than or equal to 25% of laboratories; the methods used could be improved to make the results more timely and consequently more clinically relevant. PMID- 1624573 TI - Evaluation of the autoSCAN-W/A system for rapid (2-hour) identification of members of the family Enterobacteriaceae. AB - We evaluated the ability of the Baxter autoSCAN-W/A System (MicroScan Division, Baxter Diagnostics, Inc., West Sacramento, Calif.) to use the rapid (2-h) gram negative identification panel for accurate identification of members of the family Enterobacteriaceae. At 2 h, 353 of 467 (75.6%) strains in a challenge set of biochemically typical and atypical stock cultures were correctly identified to genus and species. Another 76 (16.3%) strains were correctly identified to genus and species after the performance of recommended additional biochemical testing. Thus, at 24 h, 91.9% of the 467 strains were correctly identified. Twenty-two strains (4.7%) were identified to the correct genus but the incorrect species, and 16 strains (3.4%) were misidentified. Of these 16 strains, 9 were incorrect at 2 h, and 7 were incorrect after the additional testing. Because the system is based on fluorogenic substrates, no conventional tests were readily available with which to compare aberrant reactions. These results suggest that the autoSCAN W/A with its rapid gram-negative panels is acceptable for the identification of the Enterobacteriaceae in a clinical microbiology laboratory. PMID- 1624574 TI - Enzyme-linked immunoelectrotransfer blot test for diagnosis of human hydatid disease. AB - Sera from 71 patients with surgically confirmed hydatid disease (which is caused by Echinococcus granulosus) were studied by an enzyme-linked immunoelectrotransfer blot (EITB) assay. Sera from patients either with other cestode infections or with another illness were used as controls. Results of the EITB test for hydatidosis were compared with those of the double-diffusion (DD5) test and an enzyme-linked immunosorbent assay (ELISA). In the EITB assay with bovine lyophilized hydatid fluid, three antigen bands of 8, 16, and 21 kDa were diagnostically important. The sensitivity of the assay by using these antigen bands was 80% for hepatic cysts, 56% for pulmonary cysts, and 56% for cysts located in multiple organs. In sera from controls, the specificity of the EITB assay was 100%. Cross-reactions to the 8-, 16-, and 21-kDa bands occurred, respectively, in 12, 4, and 4% of sera from patients with cysticercosis. No cross reactions were noted in patients infected with Hymenolepis nana. The ELISA in which swine hydatid fluid was used as the antigen was as sensitive as the EITB test but was less specific (80%) and frequently cross-reacted with sera from patients with other cestode infections. The sensitivity of the DD5 test, which uses sheep hydatid fluid, was low (47%) , but its specificity was as high as that of the EITB assay. However, in patients with cysticercosis, cross-reactions were observed in 23% of sera tested. Despite the higher sensitivity found with the EITB assay, 23% (n = 5) of the serum samples that were positive by the DD5 test were not detected by the EITB assay. The EITB assay offers greater sensitivity and specificity than do the ELISA and the DD5 test. The highest proportion of hydatid cases is detected when the EITB and DD5 tests are run simultaneously. PMID- 1624575 TI - Evaluation of the Autoscan Walkaway system for rapid identification and susceptibility testing of gram-negative bacilli. AB - We evaluated the performance of the Autoscan Walkaway (W/A) system (MicroScan, Sacramento, Calif.) in conjunction with the fluorometric Neg Combo panels for rapid identification and susceptibility testing of gram-negative bacilli. Fermentative and nonfermentative gram-negative bacilli were tested in parallel with the W/A system and the Cathra Repliscan replicator (C/R) system (Cathra, St. Paul, Minn.). Conventional biochemical testing and agar dilution testing were used to resolve the identification and susceptibility testing discrepancies. Of 495 clinical isolates tested, 445 (90%) were correctly identified by the W/A system and 483 (98%) were correctly identified by the C/R system. Repeat testing by using updated versions of the W/A system's computer identification software failed to demonstrate improved identification accuracy. For susceptibility testing, the W/A system demonstrated 5.6% total interpretative category errors, including only 0.9% major and very major errors. The comparative C/R system produced only 1% errors overall, including 0.2% major and very major errors. Although the W/A system is highly automated and is capable of producing results rapidly, our findings suggest that additional identification and susceptibility testing refinements are needed before the system will be suitable for routine use. PMID- 1624576 TI - Statistical analysis of the incidence of positives in the examination of parasitological specimens. AB - Results of the examination of 2,000 parasitological specimens were analyzed for differences between results obtained by a technologist working in parasitology only and those obtained by general microbiologists who were also performing other laboratory work. The relative share of specimens determined to be positive by the specialist was approximately twice as high as the relative share determined by the general microbiologists. PMID- 1624577 TI - Involvement of Gardnerella vaginalis in urinary tract infections in men. AB - Fifteen male patients from whose urine samples Gardnerella vaginalis was isolated (clinical incidence of 0.1%) were evaluated for clinical signs and symptoms of urinary tract infection and modality of acquisition of the organism. Ten of 15 (67%) patients were symptomatic or had signs of inflammation as manifested by an increased number of urinary neutrophils. One patient had two bouts of infection caused by this organism which required two courses of antibiotic therapy. Colonies of diphtheroidlike organisms found in urine cultures should not be ignored as insignificant but should be further investigated to determine whether G. vaginalis is present. PMID- 1624578 TI - Fatal Legionella maceachernii pneumonia in Canada. AB - A case of pneumonia and acute tubular necrosis was caused by an initially unknown species of Legionella. The organism was later identified as Legionella maceachernii by a combination of cultural, biochemical, and serological methods along with a gas-liquid chromatographic profile. PMID- 1624579 TI - Graft-related endocarditis caused by Neosartorya fischeri var. spinosa. AB - The first case of endocarditis caused by Neosartorya fischeri var. spinosa is reported. The patient was a child who received a calf pericardium graft after removal of a previously inserted Dacron graft associated with deterioration of adjacent tissue. Copious vegetations removed from the heart were found to be composed of septate hyaline fungal filaments. The fungus was recognized in culture by its bivalved, winged, spiny ascospores, its Aspergillus fischerianus anamorph, and its thermotolerance. PMID- 1624580 TI - Pseudomonas mendocina, an environmental bacterium isolated from a patient with human infective endocarditis. AB - Pseudomonas mendocina has been isolated from soil and water samples. Although it has been recovered from some human clinical samples, its pathogenic role has not yet been documented. We report the first known case of endocarditis in humans due to P. mendocina. PMID- 1624581 TI - Epidemiological analysis of serologically determined rotavirus and enterotoxigenic Escherichia coli infections in Ecuadorian children. AB - The statistical association of rotavirus- and enterotoxigenic Escherichia coli specific serum antibody with demographic and hygienic factors was tested in Ecuadorian children enrolled in a cross-sectional survey. In 7- to 10-month-old children, enterotoxigenic E. coli-specific antibody was associated (P less than 0.05) with poor drinking water quality, lack of a sewage system, and feeding of supplementary food. In 7- to 14-month-old children, rotavirus-specific antibody was associated only with family size but notably not with hygienic factors. PMID- 1624582 TI - Evaluation of a competitive enzyme immunoassay for detection of Coxiella burnetii antibody in animal sera. AB - A competitive enzyme immunoassay (CEIA) was established and compared with other serological techniques for detecting Coxiella burnetii antibody in camels, goats, and sheep. This technique was evaluated because a conjugated anti-camel immunoglobulin was not available to serve as a direct signal for the demonstration of antigen-antibody reaction. A C. burnetii antibody-positive human serum and a peroxidase-conjugated anti-human immunoglobulin G were used as an indicator system competing against antibody in animal serum or as an indicator of the absence of antibody. Sera were considered antibody positive when the A414 of the test sera plus the competing positive antibody was less than or equal to 50% of the A414 of the negative-control serum plus the competing antibody. Antibody to C. burnetii was repeatedly demonstrated in 66% of camel serum samples (n = 200) by the CEIA. Among 48 camel serum samples, 71% were positive for antibody by CEIA versus 65% by EIA using peroxidase-labeled protein A. The CEIA detected C. burnetii antibody in 63% of sheep serum samples (n = 40) and in 50% of goat serum samples (n = 96), while the indirect fluorescent-antibody technique detected antibody in 38% of sheep and 34% of goat serum samples and the EIA detected antibody in 50% of sheep and 35% of goat serum samples. These data indicate that the CEIA is a reliable and sensitive technique for demonstrating C. burnetii antibody in camels, sheep, and goats. PMID- 1624583 TI - Isolation of vibriostatic agent O/129-resistant Vibrio cholerae non-O1 from a patient with gastroenteritis. AB - A strain of Vibrio cholerae non-O1 was isolated from a 48-year-old male in California who presented with a chief complaint of watery diarrhea. Laboratory investigations of this strain revealed the bacterium to be resistant to trimethoprim-sulfamethoxazole and to the vibriostatic agent O/129 (2,4-diamino 6,7-diisopropylpteridine). PMID- 1624584 TI - Evaluation of microbiological processing of urine specimens: comparison of overnight versus two-day incubation. AB - In this study the value of urine culture incubation for 1 versus 2 days was determined. The results of the study indicate that 1 day of incubation is reliable if (i) all specimens are incubated for a full 24 h, (ii) all specimens with less than 10(4) uropathogens per ml are incubated for an additional day to ensure accurate quantitation, and (iii) specimens from patients with suspected funguria are incubated for a minimum of 2 days. PMID- 1624585 TI - Sensitive and specific polymerase chain reaction assays for diagnosis of human T cell lymphotropic virus type I (HTLV-I) and HTLV-II infections in HTLV-I/II seropositive individuals. AB - To confirm and differentiate between human T-cell lymphotropic virus type I (HTLV I) and HTLV-II infections, we analyzed by polymerase chain reaction (PCR) samples of peripheral blood lymphocytes from 98 individuals seropositive for HTLV-I/II using pol (SK110/111) and tax (SK43/44) consensus primer pairs. A total of 96 samples (97.9%) were positive by the tax generic probe, while 95 were typed by the HTLV-I and HTLV-II pol probes. The three pol-negative samples were successfully amplified and typed by nested PCR with primers internal to SK110 and SK111. Results of PCR with a lysate of leukocyte nuclei obtained by whole blood lysis were comparable to those obtained with peripheral blood lymphocytes from 16 HTLV-seropositive subjects. PMID- 1624586 TI - Humoral responses against the 85A and 85B antigens of Mycobacterium bovis BCG in patients with leprosy and tuberculosis. AB - Immunoglobulin G antibodies against the 85A and 85B components of the Mycobacterium bovis BCG antigen 85 complex separated by isoelectric focusing were investigated in serum samples from 129 patients representing the major forms of leprosy, 111 tuberculous patients, and 153 healthy subjects. For both of the antigens, a higher degree of staining was observed for lepromatous leprosy patients and patients with active tuberculosis than for the other groups. Because sera from some healthy subjects recognized the 85A antigen, we suggest that antigen 85B is the most useful component of the antigen 85 complex for the serodiagnosis of the multibacillary forms of leprosy or of the active forms of tuberculosis. PMID- 1624587 TI - Comparison of a modified adherence assay with existing assay methods for identification of enteroaggregative Escherichia coli. AB - Localized, diffuse, and aggregative adherence patterns of Escherichia coli identified with specific DNA probes were compared in cell culture adherence assays by using the Center for Vaccine Development, Baltimore, method, the University of Texas Medical School, Houston (UTH), method, and a modified UTH method. Increasing postwash incubation time from 2 to 4 h in the modified UTH method allowed identification of enteroaggregative E. coli, which was otherwise not identified by the original UTH method. PMID- 1624588 TI - Stability of the recombinant hepatitis B core antigen. AB - The recombinant gene for hepatitis B core antigen (HBcAg) was cloned and expressed, and the protein was purified from Escherichia coli cultures. Purified HBcAg was tested for the effects of various physical and chemical agents on its immunoreactivity by a paramagnetic particle-based enzyme immunoassay. Recombinant HBcAg retained its immunoreactivity when heated at 70 degrees C for 60 min but was inactivated at 85 degrees C in 10 min. It was stable between pHs 5 and 10.5 but not at pHs 2 and 13.5. Treatment with sodium dodecyl sulfate (SDS), ethanol, and methanol caused a significant loss in HBcAg reactivity. The proteolytic enzymes papain and bacterial protease (type VIII from Bacillus licheniformis) degraded HBcAg significantly, but trypsin and chymotrypsin did not. The effect of combined SDS and 2-mercaptoethanol on recombinant HBcAg was an immediate loss in immunoreactivity, followed by rapid recovery to about 50% of the initial level. This level was maintained for 24 to 48 h and was followed by an almost total loss of HBcAg in about 120 h. PMID- 1624589 TI - Superficial temporal artery biopsies. PMID- 1624591 TI - Clinical applications of molecular biology to diagnostic microbiology. PMID- 1624590 TI - Pathogenesis of idiopathic myelofibrosis: role of growth factors. PMID- 1624592 TI - Methods used in the United Kingdom for the culture of micro-organisms from blood. AB - AIMS: To survey blood culture methods in use in the United Kingdom. METHODS: A questionnaire was distributed to the 415 United Kingdom laboratories participating in the clinical bacteriology subscheme of the UK National External Quality Assessment Scheme for Microbiology. RESULTS: Two hundred and eighty seven laboratories completed the questionnaire. The responses indicated wide variations in methods used including considerable differences among laboratories using the same basic methods. The most widely used techniques were the Bactec and conventional broth systems. CONCLUSIONS: Although many published comparisons have failed to show that any basic method is outstandingly successful in the isolation of all organisms, there is evidence that several factors can contribute to good performance. In some laboratories suboptimal conditions were in use. The variations in technique probably reflect differences in practical suitability of a system for any particular laboratory, costs, and personal preferences. PMID- 1624593 TI - Clinical comparison of Sentinel, a novel blood culture system, with radiometric Bactec 460 and Isolator 10 in the detection of streptococcal and anaerobic bacteraemias. AB - AIMS: To compare the performance of the Sentinel blood culture system with two other systems for the recovery of streptococci and anaerobes. METHODS: Blood cultures were taken from 55 patients one to two minutes after dental extraction. The samples were tested by the radiometric Bactec 460; the Isolator 10, which works by lysis centrifugation; and Sentinel, a fully automated system, which detects bacterial growth by changes in the voltage between two electrodes in the media. Positive samples were subcultured and streptococci and anaerobes were further identified. Terminal subcultures were performed on all negative samples. RESULTS: Sentinel was comparable with Bactec, with Sentinel recovering 20 streptococci and 14 anaerobes; Bactec isolated 26 streptococci and 15 anaerobes. The recovery of Streptococcus sanguis was significantly better from Bactec than Sentinel. The Isolator 10 recovered significantly fewer streptococci and anaerobes than either Bactec or Sentinel. Sentinel was noticeably quicker in detecting anaerobes than Bactec 460. However, there was no comparable difference with streptococci. Contaminants were recovered from 10% of Isolator 10, 2.7% of Bactec, and 7.2% of Sentinel bottles. CONCLUSIONS: Sentinel and Bactec 460 were broadly comparable in the detection of viridans streptococci and oral anaerobes, and both systems were significantly better than the Isolator 10. However, the prototype Sentinel, was significantly poorer than Bactec for the recovery of S sanguis. PMID- 1624594 TI - Evaluation of an enzyme immunoassay kit for detecting cryptosporidium in faeces and environmental samples. AB - AIMS: To evaluate a commercially available enzyme immunoassay based on a monoclonal antibody to a genus specific Cryptosporidium (IDEIA Cryptosporidium; Dako) antigen for detecting Cryptosporidium oocysts in faecal and environmental samples. METHODS: 435 human faecal samples and post-filtration deposits from 10 reservoir samples, and from six tap water samples seeded with Cryptosporidium oocysts, were examined by EIA according to the manufacturer's instructions, and by microscopic examination of phenolauramine stained smears. Samples giving discrepant results were examined by specific immunofluorescence, before and after concentration of oocysts. RESULTS: Sixteen (3.6%) faecal samples were positive by both microscopy and EIA; five (1.1%) were positive by microscopy of auramine phenol stained smears (but were not confirmed by specific immunofluorescence) and negative by EIA; one (0.2%) was positive by EIA alone, but confirmed by specific immunofluorescence; and 362 (83.2%) were negative by both microscopy and EIA. Compared with immunofluorescence positive faecal samples, the sensitivity of conventional microscopy and EIA were 94% and 100%, and specificity 76.4% and 100%, respectively. Fifty one (11.7%) were not examined by microscopy due to detection of other pathogens in a previous sample from that patient, but were found to be negative by EIA. Ten reservoir water samples (not suspected of being linked to cases of cryptosporidiosis) were negative by both microscopy and EIA. Of six samples of tap water seeded with varying concentrations of Cryptosporidium oocysts, two (10(2) and 10(3) oocysts/l) were positive by both microscopy and EIA, two (10 and 1/l) by EIA alone, and two (0.1/l and unseeded water) were negative by both microscopy and EIA. CONCLUSIONS: The kit is simple and rapid to use and offers a less subjective method than microscopy for detecting Cryptosporidium in faecal samples submitted to a busy diagnostic laboratory. PMID- 1624595 TI - Comparison of relative uses of commercial assays for Toxoplasma gondii IgM antibodies. AB - AIMS: To compare the sensitivity and user friendliness of seven commercially available enzyme linked immunoabsorbent assay (ELISA) kits for toxoplasma specific IgM. METHODS: Five antibody capture assays supplied by Abbott, Mercia, Northumbria, Organon and Sorin, and two indirect ELISA assays from Biostat and Mast, were assessed. Using defined dilutions of Toxoplasma gondii specific IgM, the performance and sensitivity of each assay was established. They were further assessed on a panel of 27 sera with a range of dye test and IgM results (as determined by the Scottish Toxoplasma Reference Laboratory). All of the assays were performed by three experienced operators and assessed for user satisfaction. RESULTS: The Mast, Organon, and Abbott assays were of low sensitivity; the Mercia and Northumbria were of high sensitivity; and the Biostat and Sorin assays produced too many false positive results. The Mercia kit provided most user satisfaction; the Mast and Abbott assays were most difficult to use. CONCLUSIONS: Local laboratories investigating toxoplasma infection should have three tests: one IgG and two IgM (high and low sensitivity) to help in the timing of infection. Alternatively, one sensitive IgM assay, such as that of Mercia, could be used by selecting appropriate high and low thresholds. PMID- 1624596 TI - Comparison of immunodiffusion and enzyme linked immunosorbent assay in the detection of abnormal antibodies in pigeon breeder's disease. AB - AIMS: To compare the sensitivity of two methods for the detection of serum antibodies to pigeon faecal antigens in patients with pigeon breeder's disease. METHODS: Serum samples stored at -20 degrees C from 50 patients with pigeon breeder's disease, 50 control samples from patients with other respiratory diseases, and 50 healthy blood donors were examined for the precipitating antibodies and IgG antibodies to antigens present in extract of pigeon droppings by immunodiffusion and enzyme linked immunosorbent assay (ELISA), respectively. RESULTS: Both antigen preparations of pigeon dropping extract were equally effective. A positive immunodiffusion reaction gave one or more precipitin lines and these antibodies were detected only in undiluted sera from 80% of the patients with pigeon breeder's disease. In the ELISA the sera were tested at a starting dilution of 1 in 100 because positive reactions were observed with sera from healthy blood donors at lower dilutions. All sera which gave optical density readings above 3 SD of the control value were considered to have IgG antibodies. These antibodies were detected in sera from all the patients with pigeon breeder's disease. The antibody titres were much higher in those patients who had precipitating antibodies (range 800-51,200) than those without (range 100-800). The antibodies were not detected in the sera of patients with respiratory diseases or healthy blood donors by either method. CONCLUSIONS: Antibodies to pigeon dropping antigens were detected by immunodiffusion and ELISA in sera from patients with pigeon breeder's disease but not in control sera. ELISA was a more sensitive method for detecting antibodies and therefore seems to have considerable potential as a routine technique in the serological diagnosis of pigeon breeder's disease. PMID- 1624597 TI - Histological and electron microprobe studies of mineralisation in aluminium related osteomalacia. AB - AIMS: To determine a possible mechanism to explain the presence of aluminium lines within fully calcified bone in aluminium-related osteomalacia. METHODS: Fifty five bone cases shown by bone biopsy to be aluminium-related osteomalacia were studied. In 38 specimens aluminium lines were identified within calcified bone by means of the Aluminon stain and a characteristic form of patchy mineralisation was seen within thickened osteoid seams. Five representative examples were analysed quantitatively by histomorphometry and electronprobe X-ray microanalysis and compared with five cases of vitamin D deficiency-related osteomalacia which also had patchy mineralisation. RESULTS: The patchy calcification occupied 40 +/- 8% (mean +/- SEM) of the osteoid and consisted of small focal deposits (less than 40 microns diameter), often (52%) around osteoid osteocytes (probably an underestimate of the association), and larger areas that extended to the aluminium lines at the underlying mineralisation front. Small and large mineralisation nuclei were seen ultrastructurally in the patchy calcification. Quantitative electronprobe X-ray microanalysis showed that calcium concentrations and calcium:phosphorus ratios in the mineralisation nuclei and in the superficial layer of the fully calcified bone of the aluminium-related osteomalacia cases were significantly less than values measured at similar sites in the vitamin D deficiency-related osteomalacia cases. Furthermore, aluminium could not be detected by means of this technique at the mineralisation front or along cement lines in these specimens. CONCLUSIONS: Calcification can occur in thickened osteoid seams in osteomalacia. It can begin around osteoid osteocytes as small deposits that enlarge within the osteoid and extend to the underlying mineralisation front or cement line where aluminium lines may become trapped. Complete calcification of osteoid could account for the presence of aluminium lines within fully calcified bone. The Aluminon stain appears to be a more sensitive method for the detection of aluminium in bone than electronprobe X-ray microanalysis. PMID- 1624598 TI - Expression of HLA-DR antigen in different histological types of gastric polyp. AB - AIMS: To study the expression of HLA-DR antigen in the different histological types of gastric polyps. METHODS: Ninety five cases of gastric polyps were histologically classified and examined for the presence of Helicobacter pylori, and for degree and type of inflammation. Further sections were stained immunohistochemically for HLA-DR antigen expression in the epithelium using a monoclonal antibody that was reactive to formalin-fixed paraffin wax embedded tissue. RESULTS: HLA-DR antigen was expressed in all of the inflammatory polyps studied (20/20), and in most hyperplastic (12/16) and adenomatous (4/6) polyps. Only a few fundic gland polyps (8/51) stained positively for HLA-DR antigen. Gastric polyps seem to have a greater tendency to express HLA-DR antigens than non-polypoid gastric mucosa, even after considering the factors that may affect HLA-DR antigen expression, such as inflammation and the presence of H pylori. CONCLUSIONS: Growth disturbances/polyp formation may be associated with increased HLA-DR antigen expression. PMID- 1624599 TI - Simplified method of grading primary carcinomas of the breast. AB - AIMS: To produce a simplified prognostic index for breast cancer. METHODS: A retrospective study of 105 cases of primary infiltrating breast adenocarcinoma (not otherwise specified) was performed. Mitotic counts and semiquantitative assessment of tumour necrosis, fibrosis tubule formation, nuclear pleomorphism were made in histological sections of the primary tumour. Statistical analysis was performed to determine which of these parameters best predicts the observed survival. RESULTS: Mitotic count and necrosis correlated best with survival. This allowed the formation of a simple prognostic index based on these two parameters. CONCLUSIONS: This new prognostic index, with four tumour grades, seemed to be superior to Bloom's grading method, with greater separation of the prognostic groups. In particular, there is clear segregation of a group of patients with a distinctly poor prognosis. PMID- 1624600 TI - Implications on laboratory workload of breast cancer screening. AB - AIMS: To determine whether the recommended methods for the handling of breast excision biopsy specimens from screening patients cause more laboratory work than those used for non-screening patients. METHODS: All breast excision biopsy specimens from 1990 were identified. Ninety one came from patients identified during the prevalent round of breast screening. These were compared with 127 from non-screening patients operated on by the same surgeon. The workload in terms of initial blocks taken, cases which needed extra blocks or other additional work, and the time taken for delivery of slides to the pathologist were assessed. RESULTS: The screening cases required significantly more initial blocks than the non-screening cases (8.03 v 4.95; p = 0.000001). When looking at the malignant diagnoses this difference was maintained (7.74 v 6.02; p = 0.00014). CONCLUSIONS: Excision biopsy specimens from screening patients require more laboratory work per case than those from non-screening patients. The reasons for these differences lie in the nature of the specimens and their subsequent diagnoses, and in the initial indications for biopsy. PMID- 1624601 TI - Depletion of neuroendocrine cells in rectal biopsy specimens from HIV positive patients. AB - AIMS: To compare the density of neuroendocrine cells in rectal biopsy specimens from human immunodeficiency virus (HIV) infected individuals with that of a control group. METHODS: Neuroendocrine cells in rectal biopsies were identified using an immunohistochemical stain for chromogranin and subsequently quantified using a method of linear intercept. RESULTS: Neuroendocrine cells were found to be significantly decreased in the HIV positive group. CONCLUSIONS: Loss of neuroendocrine cells may contribute to apoptotic bodies seen in this condition. This could be related to infection of these cells with HIV and could contribute to diarrhoeal disease in HIV infection. PMID- 1624602 TI - Fatal case of disseminated infection with the turtle bacillus Mycobacterium chelonae. AB - An apparently immunocompetent 78 year old woman presented with confusion, subcutaneous abscesses, and lesions of the nasopharynx. Gram positive, acid fast bacilli were isolated from her blood after 10 days' incubation. She was treated with trimethoprim-sulphamethoxazole for presumed disseminated nocardiasis but deteriorated and died. A post mortem examination showed skin and pulmonary lesions and endomyocardial fibrous plaques. Organisms isolated from the skin and lung were indistinguishable from those cultured from the blood. The organism was subsequently identified as Mycobacterium chelonae. Primary pulmonary infection and disseminated disease are rarely caused by this organism and bacteraemia is seldom documented. The clinical presentation and bacteriological and histological findings are difficult to differentiate from those of disseminated nocardiasis. Isolation of the organism may fail without prolonged incubation of initial cultures and there is a danger of its being dismissed as medically unimportant. Diagnosis is further hampered because large pulmonary foci may be poorly revealed by conventional radiological examination of the chest. PMID- 1624603 TI - Small numbers of Chlamydia trachomatis elementary bodies on slides detected by the polymerase chain reaction. AB - A method is described in which smears on slides, which had been examined previously in a direct fluorescence antibody (DFA) test for Chlamydia trachomatis, were tested by the polymerase chain reaction (PCR). Twenty four (73%) of 33 smears which contained fewer than 10 elementary bodies when examined by the DFA test were positive by the PCR. Of the nine negative smears, seven contained only one or two elementary bodies. However, single elementary bodies were detected by the PCR in seven of the 24 positive samples. Fifteen smears were negative by both methods. The ability to detect small numbers of elementary bodies by the PCR and its specificity for negative smears indicates its potential for retrospective analysis of stored, archival smears on slides. PMID- 1624604 TI - Rapid method for differentiating strains of Branhamella catarrhalis. AB - The ability of Branhamella catarrhalis to cause nosocomial infections is a matter of some controversy. The API ZYM research kit for detecting 89 enzymes was used on 49 isolates of B catarrhalis to select enzymes of potential use in differentiating clinical isolates. Twenty nine enzymes were produced by all isolates (13 strongly positive) and many of these were esterases; 16 enzymes were not detected in any isolate (40 if a more stringent criterion was used). Twenty enzymes were selected to form a prototype biotyping panel which allowed 17 different patterns of reactivity to be recognised. Of the 49, 34 isolates were confined to the three commonest patterns. Only one isolate was untypable using this panel due to lack of reactivity. A kit with these 20 substrates may be sufficiently discriminatory to be useful in the rapid study of outbreaks of infection caused by B catarrhalis. PMID- 1624605 TI - A viscometric method of measuring plasma fibrinogen concentrations. AB - A technique based on deducing the viscosity of serum from that of plasma was compared with the commonly used Clauss method. The two methods correlated closely (r = 0.914). The reproducibility of the viscometric method was slightly poorer than the Clauss technique at low fibrinogen concentrations, equal to that at medium fibrinogen concentrations, and marginally better at high concentrations. Fibrinogen can therefore be measured reasonably accurately with the viscometric method, and can be recommended as an alternative for laboratories possessing a viscometer. PMID- 1624606 TI - Occult alveolar haemorrhage in bronchopulmonary Kaposi's sarcoma. AB - Evidence of occult alveolar haemorrhage was sought by Perls's staining of bronchoalveolar lavage fluid to detect haemosiderin laden macrophages in 63 human immunodeficiency virus positive (HIV-1) men who underwent bronchoscopy. Twenty three patients had bronchopulmonary Kaposi's sarcoma; occult alveolar haemorrhage was present in 16 of these (including two in whom no tracheobronchial lesions were evident at bronchoscopy, but in whom the diagnosis was confirmed at necropsy). Forty patients had other diagnoses including Pneumocystis carinii pneumonia and bacterial pneumonia; 18 had occult haemorrhage. Occult alveolar haemorrhage seems to be a non-specific finding in HIV-1 positive men undergoing bronchoscopy. PMID- 1624607 TI - Clumping of lymphoma cells in peripheral blood induced by EDTA. AB - A peripheral blood smear from a patient with probable splenic lymphoma with villous lymphocytes (SLVL) showed clumping of lymphoma cells. The clumping was not seen in films made from unanticoagulated blood, and has not been previously described in lymphomas. The patient also had metastatic prostatic adenocarcinoma for 30 months before lymphoma was diagnosed and the clumped cells posed diagnostic problems. PMID- 1624608 TI - Parathyroid hormone related protein in hypercalcaemia of Hodgkin's disease. AB - The role of parathyroid hormone related protein (PTHRP) as a humoral mediator of hypercalcaemia was investigated in a patient with lymphocyte depleted Hodgkin's disease during an episode of hypercalcaemia, using an immunohistochemical staining technique for PTHRP on the tumour tissue and an immunoradiometric (IRMA) assay for PTHRP1-86 on the patient's plasma. The plasma PTHRP was less than 0.23 pmol/l in the range found in normocalcaemic controls, and the immunohistochemical staining was not positive for protein. PTHRP did not have a role in the pathogenesis of hypercalcaemia in this patient. PMID- 1624609 TI - The cyanide poisoning necropsy: an appraisal of risk factors. AB - Blood cyanide concentrations were measured in samples obtained from a pathologist before and after carrying out a necropsy on the body of a victim of cyanide poisoning. There was no significant increase in his blood cyanide concentration after carrying out the procedure. It is suggested that an important factor in determining the risk to those carrying out necropsies of the bodies of victims of cyanide poisoning is the amount of cyanide remaining in the stomach. There are several ways in which the theoretical risk inherent in carrying out such necropsies could be reduced, such as the use of a full face respirator, or the removal, intact, of the upper gastrointestinal tract to a fume cupboard for examination. PMID- 1624610 TI - Glove puncture in the post mortem room. PMID- 1624611 TI - Glove puncture in the post mortem room. PMID- 1624612 TI - Glove puncture in the post mortem room. PMID- 1624613 TI - Diagnostic value of fibronectin determination in cerebrospinal fluid. PMID- 1624614 TI - Audit of necropsies in a British district general hospital. PMID- 1624615 TI - Use of computers in anticoagulant clinics. PMID- 1624616 TI - Tooth fracture in vivo and in vitro. AB - The incidence, causes and methods of investigating tooth fracture are reviewed. This is a problem of increasing clinical significance, with many predisposing factors. Large restorations and extensive carious lesions tend to be associated with most fractures, with fracture incidence being higher in first permanent molars than other tooth types, especially in the lower jaw. Tooth anatomy influences fracture incidence, as does the functional force applied to cusps. Fracture risk in restored teeth may be reduced by cuspal coverage. Traditional tooth fracture investigations using destructive techniques provide valuable information; however, replica and nondestructive techniques are also of value. PMID- 1624617 TI - Wear in dentistry--current terminology. AB - There is some confusion in the dental literature concerning the phenomenon of wear which is usually considered in terms of its clinical manifestations rather than its underlying processes. The parent discipline for the study of these processes is tribology. The terms attrition, abrasion and erosion are common to both dentistry and tribology; however their meanings are different. Even within the various disciplines of dentistry there are differences in the understanding of the same terms. This article relates the dental appreciation of wear to the underlying processes. PMID- 1624618 TI - Development of dental plaque on the incisor teeth of monkeys (Macaca fascicularis). AB - Bacterial plaque which had accumulated for 0.5, 1, 2, 4, 7, 14 and 28 days was cultured from the labial surface of one of the central incisor teeth in 15 monkeys (Macaca fascicularis). Each sampling area was defined by a metal well contained within a custom-made removable acrylic block. The number (log10) of the total colony forming units (c.f.u.) increased significantly from 3.40 to 6.02 between 0.5 and 28 days. Similarly the number of streptococci increased from 2.80 to 4.79 during the same period, although when expressed as a percentage of the total c.f.u., the proportions decreased from 34.9 per cent at 1 day to 6.9 per cent at 7 days and then remained at that level. The number of micro-aerophilic actinomyces increased throughout the period of plaque accumulation and comprised 15.3 per cent of the total c.f.u. at 28 days. Neisseriae were infrequently isolated from 0.5- and 1-day-old plaque and were not recovered at more than 1 per cent of the total c.f.u. during any period of plaque accumulation. The fastest doubling time (median) of the total c.f.u. was 1.9 h (range 1.3-18.5 h). The rapid development of dental plaque after tooth cleaning emphasizes the importance of regular and meticulous oral hygiene to control the accumulation of potentially periodontopathic and cariogenic bacteria. PMID- 1624619 TI - Crown behaviour during cementation. AB - Complete seating of restorations during cementation is hindered by the need for excess cement to be expressed. It has been shown that postcementation seating is usually worse than precementation seating. Techniques have been developed to minimize this problem, including venting, die spacing and limiting cement placement, and these techniques are reviewed. The behaviour of the crown during cementation is considered, and consequences of crown cementation are discussed. PMID- 1624620 TI - Mutans streptococci in margins of fillings and crowns. AB - A significant correlation was found between the number of mutans streptococci in saliva and the proportional distribution of these microorganisms in pooled plaque from the margins of all restorations. At high salivary numbers there was a tendency towards a higher porportion of mutans streptococci in plaque from the margins of separate restorations. At low and medium salivary numbers, plaque samples could, however, contain greater than 10 per cent mutans streptococci and even less than 1 per cent was found in plaque from margins of restorations at high salivary numbers. The reproducibility of the plaque sampling method was good. Plaque material collected on different occasions from the same margins did not vary significantly in terms of proportions of mutans streptococci. The numbers of mutants streptococci in plaque samples from different restorations of the same kind collected on the same occasion in the same mouth could, however, show a considerable variation. The observations made in this study, indicate that a low salivary number of mutans streptococci does not exclude a high proportion of these microorganisms in plaque from the margins of separate restorations. This has to be considered when efforts are made to reduce the risk of recurrent decay. PMID- 1624621 TI - Provision of domiciliary dental care for the older person by general dental practitioners in Scotland. AB - The databank at the Scottish Dental Practice Board (SDPB) was explored to determine the domiciliary care provided, for those patients over 70 years of age, by general dental practitioners under the National Health Service in one year. Three thousand nine hundred and forty-three (3943) courses of treatment were provided, via domiciliary visits to patients in this age category, by 38 per cent (1012) of dentists registered to provide dental care under the National Health Service. Whereas 34 per cent of dentists under 40 years of age provided domiciliary care, 46 per cent of those over 40 years provided such a service (P less than 0.001). In Scotland, approximately 1 per cent of 70-79-year-old patients and 2 per cent of patients over 80 years received domiciliary dental care over a 1-year period. For those elderly people who received such care, the mean percentage doubled for every 5-year increase in patient age. PMID- 1624622 TI - Marginal accuracy of CAD/CAM inlays made with the original and the updated software. AB - The software driving the Cerec CAD/CAM system has recently been updated. In this study, the marginal accuracy of computer-machined porcelain inlays was determined using the original and the updated software. Two types of MOD cavities in Frasaco resin teeth were prepared with either sharp or rounded box corners. The distance of the occlusal and proximal marginal interface was determined using a measuring microscope. The mean occlusal interfacial distance was 52 microns for both programs. Only the box corners showed a significantly larger space, of which the mean value was approximately 200 microns. The updated version improved the marginal accuracy at the box corners. Further reduction of the interfacial distance was accomplished by rounding the sharp box corners. PMID- 1624623 TI - Effects of polymerization contraction in composite restorations. AB - Post-gel polymerization contraction of resin composite induces contraction stresses at the composite-tooth bond and in surrounding tooth structure. Strain gauges have been shown to be an effective method for measuring linear post-gel polymerization contraction of composites. A new model was developed in which the composite sample was bonded to and circumscribed by an acrylic ring. The model simulates a composite restoration surrounded by dentine. A strain gauge measured the deformation of the ring while a second strain gauge simultaneously recorded the dimensional change of the sample. Stresses placed on the acrylic ring as a result of polymerization contraction of the composite were calculated, based on the strains on the ring and the ring's material properties. Four composites (Heliomolar, Vivadent, Tonawanda, NY, USA; Herculite XR, Kerr Manufacturing Co., Romulus, MI, USA; P-50, 3M Co., St Paul, MN, USA; Silux Plus 3M Co.) were evaluated for polymerization contraction strain and stress on the surrounding acrylic ring during polymerization. At the end of the 60 s light application, Heliomolar demonstrated significantly lower post-gel contraction (0.12 per cent, P less than 0.05) when compared to the other materials. When the strain reached an equilibrium at the end of 14 min Heliomolar continued to demonstrate lower post-gel contraction, however this was not statistically significant at P less than 0.05. When the contraction stress on the surrounding acrylic ring was considered, P-50 rapidly developed and produced the largest stress values (1.7 MPa) at the end of the light application while Heliomolar produced the lowest stress values (0.3 MPa). These values, however, were not significantly different when evaluated statistically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1624624 TI - Curing light performance and polymerization of composite restorative materials. AB - The majority of modern composite restorative materials require light activation for polymerization. Variables affecting light energy absorption by the composite have been examined for their effect on the polymerization contraction. Since the polymerization contraction is closely associated in a complex way to the degree of cure of the restoration, this parameter served as an empirical indicator for the extent of polymerization. Variables included the composite shade, distance between the light source and composite sample, and light intensity. Three resin composites are evaluated. Post-gel polymerization contraction was evaluated using a strain gauge method. Curing light intensity diminished rapidly for distances greater than 2 mm between the tip of the light guide and material surface. A linear relationship was demonstrated between polymerization contraction and light intensity. The polymerization contraction of a microfilled composite and posterior composite, using a constant curing time and light intensity, decreased linearly with increasing sample thickness. Less than optimal light output of the curing light source can be compensated by increasing application time within reasonable limits. PMID- 1624625 TI - Effect of impression tray design upon the accuracy of stone casts produced from a single-phase medium-bodied polyvinyl siloxane impression material. AB - The study examined the accuracy of stone casts produced from impressions taken in stock polycarbonate trays, some of which had been strengthened with autopolymerizing polymethyl methacrylate resin and four designs of custom-made trays. Impressions of an acrylic master model of the mandibular arch on which two extracoronal crown preparations and one intracoronal inlay preparation had been carried out were taken using a medium-bodied polyvinyl siloxane material. Each preparation had been intended with a reference point for later measurement. Five impressions were taken for each type of tray and these were cast in die-stone after 24 h. The distances between the points were measured with a reflex microscope and the means determined for each design of tray. The mean difference between casts produced from the various tray designs and the acrylic master model were determined for each of the distances between the three measuring points. Statistical analysis showed that, with the stock trays, there were no significant differences between any of the modifications, or between them and the acrylic model, for any of the three distances (P greater than 0.1). When the results from the custom-made trays were analysed there were statistical differences between the acrylic model and the casts from the unperforated tray with no stops (P = 0.02), and between the unperforated tray with no stops and the perforated with stops for the distance A-B (P less than 0.01). There were no other significant differences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1624626 TI - [Teaching of geriatric dentistry; training of "mobile dental service" dentists]. AB - Quebec presently has 650,000 people over 65 years of age and as many as 900,000 will be alive at the beginning of the 21st century. Quebec epidemiological studies have shown that this group's dental condition is very poor. They feel no need to see a dentist, but 96% of them need treatment and the time elapsed since their last dental visit averages 13 years. It is forecasted that the dental needs of this group will rise, not only because of their increase in number but also because they will retain more teeth. Training in geriatric dentistry is presently deficient in the United States, Canada and particularly Quebec. Researchers have concluded, after studying the U.S. dental schools' current status of geriatric dentistry educational activities, that unless dental students receive training in geriatrics while at dental school, it is likely that they will not treat a lot of seniors in their practice. The teaching of geriatric dentistry is in full swing in the U.S. but knows a difficult birth in Quebec. There is no formal, extensive training program in geriatric dentistry given by the three dental schools in the province. Practicing geriatric dentistry requires special knowledge and skills. If treatment is to be successful, the practitioner must adopt a humanitarian approach and develop close relations and a better understanding of the feelings and attitudes of the elderly. The dentist must know and understand the special dental problems that makes them different from other groups. PMID- 1624627 TI - [Cholesterol demystified]. AB - A favorite subject of newspapers, periodicals or television programs, is that cholesterol has invaded our lives. Although well known as being undesirable, for blocking the arteries and contributing to cardiovascular diseases which kill thousands of Canadians each year, the flood of information of diverse quality leaves most of us puzzled. This paper aims to answer the main questions about cholesterol, trying to better define its relationship to cardiovascular diseases and to provide useful dietary advice to help control this risk factor. PMID- 1624628 TI - Recurrence rates of treated basal cell carcinomas. Part 4: X-ray therapy. AB - This is the fourth report in a series that reviews the experience in the Skin and Cancer Unit, from 1955 through 1982, with the treatment of basal cell carcinomas (BCCs). It concerns 862 primary (previously untreated) BCCs irradiated by a "standardized" x-ray therapy schedule. The overall 5-year recurrence rate for these lesions, as determined by the modified life-table method, was 7.4%. This rate was not significantly different from that experienced with 211 recurrent (previously treated) BCCs with a re-recurrence rate of 9.5% (P = .552). For the primary BCCs, multivariate analysis showed that increasing BCC diameter was the only independent risk factor for high recurrence rates (P = .003). The patient's age or sex, the duration of the BCC, the anatomic site of the BCC, or time-span treated (1955-1963, 1964-1972, 1973-1982) did not significantly affect the recurrence rate. Additional analysis showed that BCCs on the head less than 10 mm in diameter had a 5-year recurrence rate of 4.4% whereas those 10 mm or greater in diameter had a rate of 9.5%. Lastly, the proportion of recurrence-free treatment sites with a good or excellent long-term cosmetic outcome after x-ray therapy (63%) was lower than previous reports in this series with curettage electrodesiccation (91%) and surgical excision (84%). Thus, if the long-term cosmetic outcome after treatment is not an overriding concern to the patient, x ray therapy is an effective modality for many primary and recurrent BCCs. PMID- 1624629 TI - Basal cell carcinoma treated with Mohs surgery. A comparison of 54 younger patients with 1050 older patients. AB - The average age of patients with basal cell carcinoma (BCC) is over 60 years, and fewer than 5% of patients with this tumor are under 30 years of age. A comparison of younger (15 to 30 years) and older (56 to 70 years) patients with BCC was conducted to identify specific tumor or host features associated with BCC occurring early in life. According to data collected over an 11-year period, 54 of 2728 (2%) BCCs occurred "de novo" in younger patients. In contrast to the predominantly male older group, most of the younger patients were female. An increased use of tanning booths and hair-dyes was associated with the younger patients (P less than .001). More overall sunlight exposure and actinic keratoses were associated with the older patients (P less than .01). Defect and lesion sizes were smaller (P less than .01) in the younger group. Location, histology, and clinical morphology did not differ appreciably between the two groups. De novo BCCs in younger and older patients are similar, although some differences do exist. PMID- 1624630 TI - Sunscreens and the prevention of ultraviolet radiation-induced skin cancer. PMID- 1624631 TI - Hyperbaric oxygen and Mohs micrographic surgery in the treatment of osteoradionecrosis and recurrent cutaneous carcinoma. AB - Recurrent basal cell carcinoma (BCC) overlying bony structures which has been treated with radiation may be complicated by tumor invasion of bone and osteoradionecrosis. The authors present a case of recurrent BCC in which Mohs micrographic surgery and reconstructive surgery were augmented with pre- and post operative hyperbaric oxygen therapy. PMID- 1624632 TI - Immunotherapy and skin cancer. PMID- 1624633 TI - Consensus paper on venous leg ulcer. The Alexander House Group. AB - This is a condensed consensus report, summarizing the present status of various aspects of epidemiology, diagnosis, and treatment of venous ulcers. There are conflicting results regarding the prevalence of venous ulcers ranging from 0.18 to 1.3%, depending on the types of ulcers reported. With regard to macrovascular changes preceding venous leg ulceration, ambulatory venous hypertension is the common pathway, usually related to incompetent perforating veins and the deep venous system. Obstruction of the deep venous system seems to be less frequently related to venous ulcers. Microvascular changes have been recently studied in more detail; morphologic as well as functional changes are summarized and considered from the viewpoint of various hypotheses, including fibrin cuff, leukocyte adhesion, etc. Various investigational approaches are summarized and recommendations for the most cost-effective diagnostic tests are given. Finally, conservative medical as well as surgical treatment avenues are evaluated. Emphasis is given to the normalization of ambulatory venous pressure by sclerotherapy, ligation, or other surgical procedures, in addition to compression. The consensus report is concluded by detailed recommendations for future clinical trials. PMID- 1624634 TI - Topical use of human recombinant epidermal growth factor (h-EGF) in venous ulcers. AB - A great deal of interest has been focused recently on the potential use of synthetic polypeptide growth factors to stimulate healing of chronic wounds. In this pilot double-blind randomized study conducted at a single center, we used human recombinant epidermal growth factor (h-EGF) to treat 44 patients with venous ulceration of the lower extremities. An aqueous solution (10 micrograms/mL) of h-EGF was applied topically to the ulcers twice a day until healing occurred or for a maximum of 10 weeks. Patients were evaluated weekly for measurements of ulcer size and for the formation of granulation tissue suitable for grafting. Nine patients were excluded from efficacy evaluation because of protocol violations. Therefore, 35 patients (17 h-EGF, 18 placebo) were evaluable for efficacy, and 44 patients (22 h-EGF, 22 placebo) were available for safety. The median baseline ulcer size for all patients was 18.5 cm2, and was not significantly different between h-EGF and placebo group (12.9 cm2 versus 19.2 cm2, respectively, P = .27). By study end, six (35%) of h-EGF treated patients and two (11%) in the placebo group had healed completely (P = .10). Another 6 patients (2 of 17 h-EGF, 4 of 18 placebo; P = .50) developed healthy granulation tissue that was suitable for grafting. The median ulcer size reduction was 7% for h-EGF versus 3% for placebo per week (P = .29), and 73% versus 33% at study end (P = .32). No untoward side effects were related to the application of h-EGF. We conclude that topical application of h-EGF, in the dose and manner used in this study, was safe but failed to significantly enhance re-epithelialization of venous ulcers. However, a greater reduction in ulcer size and a larger number of healed ulcers with the use of h-EGF are encouraging results. PMID- 1624635 TI - The Bulletin of the North American Society of Phlebology. Insurance Advisory Committee Report. AB - The treatment of varicose veins as taught within the specialty of phlebology consists of the best combinations of sclerotherapy and surgery after a thorough evaluation by physical examination and Doppler ultrasound, as well as other techniques. Although patients can experience some relief of symptoms by external compression hosiery, only treatment that closes up leaky valves will stop the progression of disease. Sclerotherapy is a safe, well-accepted, non investigational, highly effective method to treat abnormally enlarged veins. Surgical procedures may be necessary to supplement sclerotherapy in certain anatomic sites. Varicose veins cause patients to experience pain, lose time from work, and can ultimately lead to permanent disability. Our healthcare system must provide the most high quality cost effective care for these patients. By keeping costs down as compared with full-scale surgical procedures, the approach of sclerotherapy or sclerotherapy with outpatient surgery, performed by properly trained physicians, provides a means to accomplish this. Medical necessity criteria allow exclusion of payments for patients seeking treatment purely for cosmetic needs. PMID- 1624636 TI - Recurrent varicose veins. Part 1: Evaluation utilizing duplex venous imaging. AB - There is the need to develop a universally accepted standard investigation for recurrent varicose veins. Duplex venous imaging offers a precise, non-invasive technique to make anatomic and hemodynamic diagnoses. A routine protocol of duplex imaging of recurrent varicose veins is described based on the known recurrent sources of reflux from deep to superficial veins. Results from this protocol indicate that incompetent perforating veins are the most common site of reflux from deep to superficial veins in patients with recurrent postsurgical varicose veins. Other important sites of reflux detected by this method are recurrent communications with the common femoral vein, the saphenopopliteal junction, and incompetent pelvic veins. Duplex imaging is recommended as a safe, non-invasive method of evaluating recurrent varicose veins. PMID- 1624637 TI - Total upper lip reconstruction with bilateral fan flaps. AB - Reconstruction of the total upper lip may be easily performed using fan flaps. However, two details must be taken into consideration: 1) the wide pedicle in the commissural angle, including the facial artery, must be designed, and 2) the mucosal flap must be 8 mm longer, in the inner portions, than the skin flap used to reconstruct the lip semimucosa. PMID- 1624638 TI - The vertical wedge biopsy. AB - A biopsy technique is described that has been used in my clinical practice thousands of times. This very simple, cost-effective technique employs only one surgical tool, the scalpel blade, and permits a biopsy to be taken with sufficient tissue for histologic analysis. In that there is no disruption of a tumor margin, it permits the physician to make a diagnosis and not limit his or her choice of therapeutic modalities. Again, I wish to stress that appropriate selection of lesions is a critical point of this technique. It is unacceptable for lesions suspected to be malignant melanoma or for dermatoses that may have a deep component. PMID- 1624639 TI - Office varicose vein surgery. PMID- 1624640 TI - Is a second dermabrasion usually necessary or not? PMID- 1624641 TI - Greek Society for Dermatologic Surgery. PMID- 1624642 TI - The Section of Dermatologic Surgery of the Polish Dermatologic Society. PMID- 1624644 TI - Cognitive function in major depression. AB - Forty patients with a major depressive episode were divided into equal endogenous and neurotic sub-groups using the Newcastle scale. They were all rated on the 17 item Hamilton scale and with a variety of neuropsychological tests. They were compared with 20 age- and education-matched control subjects. Both endogenous and neurotic groups had impaired memory function on the auditory verbal learning test; recall and recognition were equally impaired suggesting that effort was not a major determinant of performance. The endogenous group was more impaired on digit symbol substitution and the Trail making test (A and B). Impairment was correlated with symptom scores on the Hamilton and Newcastle scales, even after allowing for the effect of age. It is concluded that the conventional distinction between organic and functional impairment breaks down in severe depressive illness. The implications of this for clinical neuropsychological testing and the anatomy of the brain dysfunction in depressive illness are discussed. PMID- 1624643 TI - Life events and relapse in bipolar affective disorder. AB - In a 2 year study of life events and relapse in a cohort of 62 patients with bipolar affective disorder, an excess of events was found during the month immediately preceding relapse. Of 52 relapses 19% were preceded by a severe event in the previous month, compared to a background rate of 5% of patients experiencing a severe event each month at other times. The rate of life events prior to relapse was not apparently different between manic and depressive relapse, though the number of depressive episodes was small. PMID- 1624645 TI - Post partum blues: depressive disease or pseudoneurasthenic syndrome. AB - Depressive mood disorders following childbirth can be quantified with self-rating and observer-rating scales. During two months, in the period from November 1989 to March 1990, women admitted to the obstetric unit of the University of Wurzburg were examined on days 3 and 5 post-partum with the Hamilton Psychiatric Rating Scale for Depression, the Montgomery-Asberg-Depression-Rating-Scale and the Befindlichkeits-Scale by von Zerssen. Results reveal that during the early puerperium, scores on these scales rarely reach the same severity as in major depressive disorder. The clinical picture is no different from emotional hyperaesthetic hyposthenia following other kinds of physical illness such as endocrine disorders. PMID- 1624646 TI - The Galway Study of Panic Disorder. I: Clomipramine and lofepramine in DSM III-R panic disorder: a placebo controlled trial. AB - Among 79 volunteer, unpaid, family doctor-referred psychiatric out patients with DSM III-R panic disorder, with and without agoraphobia, 66 completed a six week placebo-controlled trial of lofepramine versus clomipramine and 57 survivors were followed up for 6 months. All subjects received one hour per week concurrent behavioural counselling in the acute phase. Of 13 dropouts in the first 3 weeks, 9 (of 27) were on clomipramine, 2 (of 26) were on lofepramine and 2 (of 26) were on placebo. The high (30%) early dropout from the clomipramine group was largely due to medication intolerance. Both drugs were superior to placebo by the end of week 6 on several standard rating scales but not on panic attack frequency. No significant differences in efficacy were found between the two drugs tested to the end of 6 months. No tendency for relapse was noted in the three months following taper-off of medication from week 12 to week 24. The study provides evidence that both drugs, in the dosages used, are superior to placebo in the acute phase of panic disorder in treatment-naive subjects concurrently receiving appropriate psychotherapy. PMID- 1624647 TI - Recall and recognition memory deficits in depression. AB - The aim of the present study was to establish the nature of memory deficits of depressive subjects in word learning tests. A word learning test consisting of 1, 3 or 5 learning trials was used. We found that patients were characterized by inferior memory recall compared to controls when 5 learning trials were given. Patients performed significantly slower than controls on a recognition test but both patients and controls recognized the same number of words. This suggests that the memory deficits that are present in many depressive subjects may be restricted to impaired active retrieval from memory. A second experiment revealed that recognition memory and delayed recall as well as immediate recall were impaired in depressive patients after 1 learning trial. These short-comings vanished after 3 trials, except for immediate recall. These data suggest that not only retrieval but also encoding of information into memory may be impaired in depression, especially in the beginning of a task when demands on cognitive effort are high. The results are discussed in terms of resource allocation and demands on effort that may change in the course of a task. PMID- 1624648 TI - Staffing patterns in hospital clinical dietetics and nutrition support: a survey conducted by the Dietitians in Nutrition Support dietetic practice group. AB - The Dietitians in Nutrition Support dietetic practice group of The American Dietetic Association administered a questionnaire to evaluate changes in nutrition support services provided to hospitalized patients and home patients in 1989 and compared the results with results of a survey administered in 1986. The 1986 survey documented an increase in tube feeding to inpatients during 1984 to 1986 and greater dietitian staffing in tertiary care hospitals than in primary care hospitals and in larger hospitals in 1986. The 1989 questionnaire was mailed to clinical nutrition managers from a nationwide random sample of 1,000 hospitals from American Hospital Association members; 271 responses were received. Full time equivalent (FTE) registered dietitians (RDs)--including clinical RDs, nutrition support service RDs, and clinical nutrition managers--decreased 11% from 1986 to 1989. FTE dietetic technicians decreased 22%. The number of FTE nutrition support service RDs and clinical nutrition managers decreased significantly (P less than .05). The mean number of FTE clinical dietitians per 100 beds decreased from 1.4 to 1.0 from 1986 to 1989. These decreases in dietetics staffing occurred despite an overall increase in total hospital FTE staff of 2.9%. Reported daily provision of nutrition support modalities to inpatients was 3.5% for parenteral nutrition, 4.9% for enteral tube feeding, and 9.6% for oral supplements. Decreased dietetics staffing was accompanied by other factors that negatively affect productivity (and therefore ability to provide adequate patient care), including inadequate delegation of technical tasks to dietetic technicians, limited availability of secretarial and computer support, and minimal provision of pocket pagers. These trends may be evidence of inadequacy of dietetics staffing to meet the needs of the US population for nutrition care. PMID- 1624650 TI - Weight-related behaviors and concerns of fourth-grade children. AB - Behaviors and concerns related to weight were measured among 457 fourth-grade children attending 10 rural schools in central Iowa. A questionnaire was used to gather data on the children's concerns about being overweight, concerns that certain types or amounts of food would contribute to their being overweight, alterations in food intake to avoid being overweight, and perceptions that peers and family members were concerned about being overweight. In addition, each child's height and weight were measured. Weight-related behaviors and concerns increased with increasing weight-for-age and body mass index (BMI) and were more prevalent among girls than boys. The frequency of drinking diet soft drinks was positively correlated with weight-for-age and BMI and tended to increase with an increase in weight-related behaviors and concerns. Girls were more likely than boys to report a desire to be thinner (60.3% vs 38.4%), whereas boys were more likely than girls to want to be taller (67.2% vs 49.1%). The desire for less body fat was significantly associated with an increase in the frequency of weight related behaviors and concerns, the frequency of drinking diet soft drinks, weight-for-age, and BMI. These findings indicate a need for interventions that combat fear of obesity and restrictive eating among growing children. PMID- 1624649 TI - Effectiveness of enteric coated pancreatic enzymes given before meals in reducing steatorrhea in children with cystic fibrosis. AB - In vitro data indicate that length of enzyme incubation with food critically affects enzyme dissolution and presumably effectiveness. This study compared the effectiveness of enteric coated (EC) pancreatic enzymes given before meals with those given during meals (15 minutes after beginning of meal) in reducing steatorrhea in well-nourished children with cystic fibrosis. Eight children (6 years 11 months old to 14 years 7 months old) were studied in the General Clinical Research Center at Indiana University Hospital, Indianapolis. A crossover study design randomly assigned enzymes before or during meals during two consecutive 7-day treatment periods for each child. No difference in fat excretion was documented for the total group when the children who took enzymes before meals were compared with those who took enzymes during meals. However, a stepwise multiple regression analysis of the difference (before minus during) in fat excretion on sex, age, enzyme number, and treatment order documented a positive correlation of age with fat excretion (r = .83). Mean fat excretion in younger children (less than 10 years old) decreased significantly when enzymes were given before meals (7.14 +/- 1.95%) rather than during meals (9.92 +/- 1.61%) (P = .004). The difference in fat excretion (mean = 2.78 +/- 0.55%, range = 1.4% to 4%) translates into a half to one full year's growth potential. Younger children with cystic fibrosis may benefit clinically from taking EC enzymes before meals. PMID- 1624652 TI - Wasting malnutrition and inadequate nutrient intakes identified in a multiethnic homeless population. AB - The few previous studies of the nutritional status and dietary intakes of the homeless have been limited by small sample sizes. We collected information from a multiethnic sample of 277 homeless men and women in Miami, Fla. Data collected included a brief personal history, anthropometric variables, and a detailed 24 hour dietary recall. An additional 24-hour dietary recall was collected from a subsample of 36 men. Socioeconomic characteristics of our sample were similar to that of other samples of the homeless. Using measurements of the upper arm muscle area, we identified wasting malnutrition in 20% of the men. Dietary intakes (percentage of the Recommended Dietary Allowances [RDAs] +/- standard error of the mean) for energy (82 +/- 2.88%), calcium (63 +/- 3.28%), zinc (56 +/- 2.61%), and vitamin B-6 (68 +/- 3.93%) were significantly below RDA guidelines for all ethnic groups. In addition, thiamin (75 +/- 6.34%) intakes for whites and vitamin A (61 +/- 12.53%) and riboflavin (74 +/- 7.72%) intakes for Hispanics were below RDA guidelines. Compared with men, women consumed significantly less energy, calcium, and zinc. PMID- 1624651 TI - A nutrition survey of and recommendations for individuals with Prader-Willi syndrome who live in group homes. AB - The purpose of this study was to describe anthropometric data and identify diet related problems of individuals with Prader-Willi syndrome (PWS) who reside in group homes. A group home is a licensed foster care facility that provides 24 hour care for the developmentally disabled. Questionnaires were sent to dietitians (or the person responsible for nutrition care) of 25 group homes; responses from 18 homes were analyzed. The mean age of residents with PWS was 25 +/- 8.4 years and the mean height was 152.4 +/- 9.7 cm. The mean weight for 19- to 22-year-old men was 75.5 +/- 26.8 kg and that for women of the same age was 74.5 +/- 20 kg. The residents consumed a mean of 1,000 to 1,500 kcal/day. Most of the group homes (n = 16) locked their kitchens at night, and in 12 of the homes stealing and hoarding of food occurred. Pica behavior (eating of nonfoods) was reported in 7 homes. One third of all residents had success in weight loss and were on a maintenance diet, but a major problem was determination of a desirable weight goal. Our key recommendations for dietitians are weigh residents weekly; use the body mass index with prescribed zones for determination of weight goals; monitor change in circumference measurements; follow the guidelines of 7 to 8 kcal/cm of height for weight loss and 10 to 14 kcal/cm of height for weight maintenance; administer 1,000 kcal/day or more and encourage daily aerobic exercise; respect food preferences while adhering to dietary prescriptions; adhere to strict food control procedures; and use nutrition education methods and an interdisciplinary approach for behavior modification. PMID- 1624653 TI - Perspectives on history: military dietetics in the Philippines during World War II. AB - The history of the profession of dietetics is a history of caring, dedicated, and capable individuals. This article examines the experiences of three dietitians during World War II in the Philippines--their pre-war status and their changing environments as the Japanese invaded the Philippines in overwhelming numbers. It recounts the extreme hardships they endured for 3 years as prisoners of war of the Japanese at Santo Tomas Internment Camp (formerly Santo Tomas University) in Manila. The article covers the time before Army dietitians had military status and concludes shortly after the former prisoners returned to the United States, when they were commissioned and promoted to the rank of first lieutenant. PMID- 1624654 TI - Review of L-tryptophan and eosinophilia-myalgia syndrome. AB - The ingestion of L-tryptophan (LT)-containing products has recently been associated with a newly diagnosed disorder known as eosinophilia-myalgia syndrome (EMS). This article reviews the pertinent research concerning the association between LT-containing products and EMS, including (a) the incidence and clinical course of EMS; (b) characteristics (eg, age and sex) of patients with EMS; (c) LT intakes (eg, dose, duration of intake) associated with EMS; (d) tracing of implicated LT-containing products to one raw material manufacturer, (e) theories related to the association, for example, the contamination theory; and (f) regulatory issues surrounding LT-containing products. The importance of this information to the dietitian is twofold. First, because LT is an essential amino acid, questions concerning LT-containing products and EMS are often directed to dietitians. Second, dietitians should be aware of the association to help facilitate the identification and care of patients with EMS. PMID- 1624655 TI - Prevalence of disordered eating in girls: a survey of middle-class children. PMID- 1624656 TI - Effect of level of lesion and quality of ambulation on growth chart measurements in children with myelomeningocele: a pilot study. PMID- 1624657 TI - Elderly veterans at risk for nutrition-related cardiovascular disease. PMID- 1624658 TI - Effect of a state dietetic association's weight management program on its members. PMID- 1624659 TI - Dietary status and eating out practices of college students. PMID- 1624660 TI - President's page: achievement...action...excellence--75 years of food and nutrition leadership. PMID- 1624661 TI - Maternity and medicine. PMID- 1624662 TI - Speak out for reproductive rights. PMID- 1624663 TI - Elizabeth Blackwell medal. PMID- 1624664 TI - Bertha Van Hoosen Award. PMID- 1624665 TI - Calcium Nutrition Education Award. PMID- 1624666 TI - Camille Mermod Award. PMID- 1624667 TI - Can children be a part of medical school? PMID- 1624668 TI - Pregnancy during residency: a look at the issues. PMID- 1624669 TI - When to have a baby: an obstetrical point of view. PMID- 1624670 TI - Who takes care of the caregiver's children? PMID- 1624671 TI - Physician pregnancy: male and female colleagues' attitudes. AB - A survey questionnaire was mailed to residents and faculty at a midwestern medical school to assess male and female attitudes toward colleagues' pregnancies. A total of 67% (N = 97) of the 145 faculty and 48% (N = 103) of the 214 residents completed surveys, yielding an overall return rate of 56% (N = 200). Among faculty, responses on only 1 of the 15 items showed a significant difference by gender. Residents' responses, however, showed statistically significant gender differences on 8 of the 15 items. More female than male residents felt that pregnant physicians maintain job performance and interest in medicine. More male than female residents believed pregnancy was disruptive to relationships with colleagues and viewed women of childbearing age as a risk to the optimum functioning of a department. The authors discuss reasons for the gender differences in attitude found among the residents and suggest possible interventions. PMID- 1624672 TI - Maternity leave: rights, rules and regulations. PMID- 1624673 TI - Physician mothers: a conceptual model for planning and coping with motherhood and medical practice. PMID- 1624674 TI - Finding HIV-infected women--the clinician's role. PMID- 1624675 TI - Plasma growth hormone (GH) responses to corticotropin-releasing hormone in patients with acromegaly--the effect of dexamethasone pretreatment and the comparison with GH responses to thyrotropin-releasing hormone, gonadotropin releasing hormone and GH-releasing hormone. AB - It has been reported that paradoxical GH responses to corticotropin-releasing hormone (CRH) occur in only few patients with acromegaly. However, we have observed such responses in 7 of 14 active acromegalic patients. Therefore, we have studied the GH responses to thyrotropin-releasing hormone (TRH) (500 micrograms, iv), gonadotropin-releasing hormone (LHRH) (100 micrograms, iv) and GH-releasing hormone (GHRH) (100 micrograms, iv) in these patients to examine the relationships between the GH responses to CRH and the responses to these hypothalamic hormones. Further, these patients received human CRH (1-41) NH2 (100 micrograms, iv) with or without dexamethasone (Dex) pretreatment (1 mg/100 ml saline, iv, from -30 to +30 min) to study the mechanism of CRH-induced GH secretion, and a perifusion experiment was performed using adenoma tissue obtained at surgery from one patient (10(-7) M CRH and TRH were added) to elucidate whether CRH acts directly at the pituitary level. Aberrant GH responses induced by CRH were found in 7 of 14 (50%) acromegalic patients (TRH responders: 10/13, 77%; LHRH responders: 2/9, 22%; GHRH responders: 10/12, 83%). In these patients, percent GH increment induced by CRH ranged from 81 to 144% (Mean +/- SE, 118 +/- 8%), and the GH peak (19 +/- 3 min) appeared as early as after TRH (23 +/- 4 min, N = 10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1624676 TI - Effectiveness and long-term tolerability of the slow release oral form of bromocriptine on tumoral and non-tumoral hyperprolactinemia. AB - The effectiveness and long-term tolerability of a new formulation of bromocriptine with slow gastrointestinal release (Parlodel SRO) has been evaluated on ten patients with macroprolactinoma, seven patients with microprolactinoma and five patients with nontumoral hyperprolactinemia during a period of 1-30 months. Six out of ten macroprolactinoma-bearing patients obtained a rapid normalization of plasma PRL levels with reduction of the tumor size recorded by CT scan follow-up. Four of six microprolactinomas and all the five nontumoral hyperprolactinemic patients became normoprolactinemic with recovery of gonadal functions while in two other microprolactinomas Parlodel SRO significantly reduced plasma PRL levels with restoration of menses. Only in two patients the treatment was withdrawn for the appearance of side effects. In conclusion, Parlodel SRO is an effective drug in the management of tumoral and nontumoral hyperprolactinemia. The good long-term tolerability together with the hypoprolactinemic activity makes this drug a very good choice therapy in hyperprolactinemic syndromes even in case of poor tolerability to the standard formulation of the drug. PMID- 1624677 TI - Evaluation of hypothalamic-pituitary function in patients with thalassemia major. AB - The increased survival of patients with thalassemia major, made possible by more adequate therapeutic regimens, has emphasized the importance of the endocrine abnormalities often associated with this disease. In twelve thalassemic patients, we evaluated the hypothalamic-pituitary function by measuring plasma levels of anterior pituitary hormones under basal conditions and in the course of provocative tests. An impairment of growth hormone (GH) secretion was demonstrated in a considerable proportion (7/12) of these patients. In some of them failure of GH response to insulin-hypoglycemia and normal hormone rise after growth hormone-releasing hormone indicate a hypothalamic defect. A defective prolactin secretion was observed in the female hypogonadic but not in the male thalassemic patients. This abnormality appears to be dependent on estrogen deficiency rather than on a hypothalamic-pituitary dysfunction. In our series a high prevalence (8/12) of hypogonadism was also noticed. In these cases, the low gonadotropin levels and their unresponsiveness to gonadotropin-releasing hormone are compatible with a hypothalamic and/or pituitary damage. Lastly, the enhanced ACTH responses to the stimuli associated to a reduced cortisol release suggest the existence, in these patients, of a diminished adrenocortical reserve. On the whole, this study has shown several derangements of the hypothalamic-pituitary function in thalassemia. This emphasizes the need for careful endocrine surveillance in this disease. PMID- 1624678 TI - Octreotide therapy of growth hormone excess in the McCune-Albright syndrome. AB - We report a patient with the McCune-Albright syndrome and growth hormone excess. Biochemical evaluation demonstrated characteristic changes typical of acromegaly, and an unusual pattern of delayed somatotropin response to hGHRH40, not previously described in this syndrome. Therapeutic trial of low-dose octreotide successfully reversed his growth hormone excess, whereas bromocriptine failed to reduce growth hormone levels. Previous reports of acromegaly and McCune-Albright syndrome are reviewed, and the unique features of this case discussed. PMID- 1624679 TI - The evolution of Graves' ophthalmopathy during treatment with antithyroid drug alone and combined with triiodothyronine. AB - We analyzed the evolution of the ophthalmopathy associated with Graves' hyperthyroidism in 45 patients treated with two different antithyroid drug regimens. Group A patients (n = 31) received either methimazole (40-100 mg daily) or propylthiouracil (400-900 mg daily) combined with T3 daily throughout treatment. Group B patients (n = 14) were treated with conventional regimen with lower doses of either methimazole (5-25 mg daily) or propylthiouracil (50-300 mg daily) and no T3 addition. Eye signs and proptosis measurement were evaluated just before the beginning of the treatment and compared with the results after antithyroid drug withdrawal. Improvement of the eye signs considered on grounds of the NOSPECS classification was greater in group A than group B (p less than 0.01). Also, the decrease in proptosis measurement was greater (p less than 0.01) in patients treated with combined regimen (21.5 +/- 2.4 mm to 20.4 +/- 2.3 mm) than in patients receiving conventional therapy (20.4 +/- 1.6 mm to 20.0 +/- 1.7 mm). Serum thyroglobulin concentrations did not correlate with either the severity or the evolution of the ophthalmopathy. Negative serum antithyroglobulin antibody (TgAb) was associated with the improvement of the ophthalmopathy that was noted in 24 out of 27 patients (Chi-Square = 5.84; p less than 0.001). Thus, serum TgAb levels might have some connection with progression of eye signs but serum Tg concentration does not. Our study suggests that in most patients the transition from hyperthyroidism to euthyroidism induced by antithyroid drug therapy is associated with the improvement of the Graves' ophthalmopathy. However, no marked difference can be drawn between the two treatment regimens. PMID- 1624680 TI - Corticosterone methyloxydase deficiency type II in a Croatian girl. AB - This is a brief case report on a four-month-old girl who was admitted for failure to thrive and moderate dehydration. On admission she was mildly dehydrated and undernourished but with otherwise normal physical findings. Laboratory investigation disclosed mild but constant hyponatremia and hyperkalemia, very high plasma renin activity (greater than 900 ng/mL per hour) and low plasma aldosterone concentration (2.5 ng/dL). The plasma 18-hydroxycorticosterone (18-OH B) was very high (1,682 ng/dL), producing thus an abnormally elevated 18-OH-B to aldosterone ratio of 542 (normally 6.3 +/- 3.6). The diagnosis of corticosterone methyloxydase deficiency type II was made, and the administration of fluorohydrocortisone resulted in rapid weight gain with normalization of blood electrolytes and gradual decrease in plasma renin activity. A very efficient catch-up growth resulted in normal body weight and length at the age of 2 years. This is the first well documented case of the disease in the population of Yugoslavia. PMID- 1624681 TI - Deceptively high thyroid hormone levels in a neonate due to autoantibodies against thyroid hormones transferred from a mother with Graves' disease. AB - At birth, a clinically euthyroid male neonate was found to have unexpectedly high levels of free T3 and T4 concurrent with a high TSH level. The mother was treated with propylthiouracil for Graves' disease during and after pregnancy. The neonate also had an extremely high titer of TSH receptor antibodies. He soon became clinically thyrotoxic as TSH levels were suppressed and thyroid hormone levels rose. After instituting antithyroid therapy, TSH levels became elevated again, while thyroid hormone levels decreased but were still above normal. Around 3 months after birth, both TSH receptor antibodies and discordance, between the levels of thyroid hormones and TSH, disappeared. Because of high maternal TSH levels in conjunction with an elevated free T3 level at 7 months postpartum, we suspected the presence of autoantibodies against thyroid hormones (AAb). Maternal and infant blood samples were then examined retrospectively for AAb and were detected in all the samples except those of the infant taken more than 3 months after birth. The authors, therefore, suggest that physicians be aware of the presence of AAb in pregnant women with Graves' disease, in order to avoid inappropriate treatment which could lead to fetal and neonatal hypothyroidism. PMID- 1624682 TI - Transplacental passage of autoantibodies to triiodothyronine. AB - Autoantibodies to T3 (T3Ab) were detected by immunoprecipitation in a 18-year-old female patient affected by Graves' disease. The presence of these antibodies was constantly confirmed during a 7-year follow-up period, independently of therapy and functional thyroid status. Antithyroid microsomal antibodies (McAb) and TSH binding-inhibiting antibodies (TBII) were also present. The title of AbT3, McAb and TBII fluctuated, at times, independently of one another. The patient became pregnant; during pregnancy T3Ab concentration fell and went up again 4 months after delivery. A normal baby was born. T3Ab were present in the cord blood and declined during the following 2-8 months. The T3Ab of both mother and child belonged to the IgG class. The concentrations and the binding affinities of T3Ab in mother and child were identical. The presence of T3Ab in the child did not affect his thyroid function. PMID- 1624683 TI - Gonadotropin evaluation in the diagnosis of polycystic ovary syndrome using either a monoclonal or a polyclonal antibody radioimmunoassay. AB - The LH/FSH ratio values between gonadotropins dosed with a monoclonal antibody assay (IRMA) in the micropolycystic ovary syndrome (PCOS), are discussed and compared to those obtained with the classic assays using polyclonal antibodies. Because of the higher selectivity of this IRMA assay it is noteworthy that the cut-off value between normal and PCOS patients is now equal to or above one. The evaluation of the LH/FSH ratio between the peak values of the two gonadotropins after a GnRH 100 micrograms iv bolus, may be useful in the diagnosis of PCOS in those patients who present an LH/FSH less than 1 in basal conditions even in the presence of clinical and ecographic aspects of PCOS. PMID- 1624685 TI - An emerging hypothesis: synergistic induction of aging by free radicals and Maillard reactions. AB - Most modern theories of aging have centered around the notion that age-related deterioration is primarily due to structural and functional modifications of cellular constituents. Among them are three currently popular hypotheses--the Free Radical, Glycation, and Maillard Theories of Aging. The first proposes that age-related effects are due to free radical reactions that damage cellular constituents, while the latter propose damage induced by nonenzymatic glycation and other Maillard reactions and the consequent modification of macromolecules as the primary cause of aging. Although these hypotheses were formulated independently, recent studies suggest that free radicals, glycation, and Maillard reactions may in fact represent partially interactive elements of a single, more complex biochemical pathway. We therefore propose the Free Radical Glycation/Maillard Reaction Theory of Aging: that age-related deterioration is produced by the sum of the damage induced by free radicals, by glycation, by Maillard reactions, and by their interactions. PMID- 1624684 TI - Diagnosis and treatment of Cushing's syndrome. Cushing's syndrome: current clinical problems, symposium. Padova, October 19-20, 1990. PMID- 1624686 TI - Cellular determinants of age-related decrements in the T-cell mitogen response of B6CBAF1 mice. AB - Age-related changes in the cellular composition of the immune system that are associated with an impaired proliferative response to T-cell mitogens were identified for B6CBAF1 mice. The frequencies of precursors of Con A-induced IL-2 secreting cells (pHTL) and of Con A-induced cytotoxic cells (pCTL), determined by limiting dilution analysis, were lower for splenocytes from old mice, as were the proliferative responses to Con A and PHA, determined in conventional high cell density cultures for the same mice. The pHTL frequency correlated with the proliferative response to Con A (r2 = .94) and to PHA (r2 = .83) among old mice, but not among young; there were no correlations of pCTL frequency with proliferative responses. The reduced pHTL frequency in old mice resulted from: (a) an age-related doubling of the number of splenic B cells that diluted T cells, and (b) a 67% decline in the absolute number of Con A-reactive pHTL cells in the spleen that appeared despite the maintenance of normal numbers of total splenic CD4+ and CD8+ cells. Thus, both a decline in absolute pHTL numbers and an increase in the number of non-T cells in the spleen result in a diminished pHTL frequency that is closely linked to the impaired mitogen response observed for old B6CBAF1 mice. PMID- 1624687 TI - Acute wound repair in an aged animal: a model for accelerated aging of the microvasculature? AB - This study of wound repair in the aged rat is based on increased carbohydrate content of various proteins which occurs with aging and is readily seen in the microvasculature (MV). We have used the periodic acid-Schiff (PAS) reaction to identify histochemically the carbohydrate moiety of the glycoproteins found in these blood vessels. In the young rat, as in other young vertebrates, elements of the MV are PAS negative and become increasingly PAS+ beyond the half life span. During acute wound repair in an old animal, the new capillaries and venules are PAS- 2 weeks after injury, moderately PAS+ at 4 weeks, and intensely PAS+ at 8 weeks. Arterioles are present and PAS+ at 6 weeks, and intensively positive at 8 weeks, comparable to vessels remote from the wound site. The MV in wound repair in a young animal remains PAS- throughout healing. Rapid aging of the microvasculature in wound repair in an old animal reproduces histochemically the aging which occurs progressively during the prior 24 months. These histochemical changes may result from successive enzymatic and nonenzymatic glycosylation of the various basement membrane proteins in the microvasculature in both normal aging and wound repair in the aged animal. The latter may serve as a model for study of accelerated aging. PMID- 1624688 TI - Accumulation of cardiac lipofuscin depends on metabolic rate of mammals. AB - The accumulation of lipofuscin, an important phenomenon during aging, suggests that the sexual maturity (puberty) of mammals is a starting point of the aging process. The rate of cardiac lipofuscin accumulation was not correlated linearly with maximum life span of mammals, but the correlation was a power function of the maximum life span. The rate of lipofuscin accumulation statistically correlated with the specific metabolic rate, and inversely correlated with the brain weight of mammals. The first appearance of lipofuscin showed a good correlation with the brain weight. However, the slope of the line was different between primates and domestic and laboratory animals. From these results, it is suggested that the accumulation of cardiac lipofuscin is dependent on the specific metabolic rate of mammals. PMID- 1624689 TI - Effects of the selective serotonin reuptake inhibitor fluoxetine on baroreceptor reflex sensitivity and body weight in young and old rats. AB - Male F344BNF1 hybrid rats (F1 crosses between female Fischer 344 and male Brown Norway rats) aged 3 or 24 months were treated with vehicle (1 ml water/kg, IP) or fluoxetine (10 mg/kg, IP) once a day for 1 day or 27 consecutive days; body weights were recorded daily. Baroreceptor sensitivity was assessed in conscious unrestrained rats implanted with vascular catheters 24 hours after the single or 27th injection by measuring peak changes in mean arterial pressure (MAP) and heart rate (HR) elicited by graded doses of phenylephrine or nitroglycerin, IV. The results demonstrate that the effects of the serotonin uptake inhibitor fluoxetine, whether administered acutely or for 27 days, are similar in young and old rats: a relative decrease in body weight, a slight decrease in resting MAP without a change in HR, and no effect on baroreceptor sensitivity. In addition, this study in F344BNF1 hybrid rats supports previous reports in inbred rat strains by demonstrating that baroreceptor dysfunction, but not hypertension, is observed in old rats. PMID- 1624690 TI - A comparison of the ventilatory responses to exercise of elderly and younger humans. AB - Elderly adults are assumed to have an exaggerated ventilatory response to exercise. This study sought to examine this assumption by comparing the steady state ventilatory and gas exchange responses of a group of elderly and younger humans. Steady-state ventilatory responses to moderate cycle ergometer exercise were measured in 14 elderly (71.0 +/- 1.3, mean +/- SEM years) and 14 younger (21.8 +/- 0.7 years) subjects. Compared with the younger group, the elderly had a significantly higher VE, VCO2, and VO2 at all work rates. In addition, delta VE/delta VCO2 was significantly higher for the elderly than for the younger subjects (31.07 +/- 1.34 vs 27.16 +/- 1.01, respectively; p less than .03), but the intercept with the ventilation axis was significantly lower (0.81 +/- 0.97 1.min-1 vs 4.15 +/- 0.77 1.min-1, respectively; p less than .015). Consequently, the VE-VCO2 relationships of the two groups crossed and the ventilatory equivalent for CO2 was similar for both groups. Thus, in these elderly subjects, the steeper delta VE/delta VCO2 was misleading because it was not associated with a greater ventilatory equivalent for CO2. In summary, although the ventilatory response of these elderly subjects to a given work rate was greater than that of the younger subjects, this was secondary to a greater metabolic requirement and cannot therefore be considered exaggerated. Furthermore, the data suggest that delta VE/delta VCO2 may be an inappropriate index of the ventilatory response to exercise in the elderly. PMID- 1624691 TI - The association of E. coli peritonitis with an impaired and delayed fever response in senescent rats. AB - Infection is one of the leading causes of death in elderly humans, and the importance of the early diagnosis of severe infection is undisputed. In the elderly a delay in diagnosis is often due to a reduced or absent fever. To understand more fully the pathogenesis of fever in senescence, we assessed the febrile response to E. coli peritonitis in 3-, 12-, and 24-month-old rats. Baseline temperatures were unchanged with age. Following infection with 1 x 10(8) CFU E. coli, a fever was evident in 2.8 h in the young, 3.9 h in the 12-month-old rats, and delayed until 5.8 h in the senescent rats. The magnitude of the fever was quantitatively less in the older rats compared with the two younger age groups throughout the time course of the fever. Because beta-adrenergic-mediated thermogenesis in brown adipose tissue has been implicated in the genesis of fever, we also assessed adenylate cyclase activity in this tissue. There was a progressive age-related decrease in both receptor- and postreceptor-stimulated adenylate cyclase activity. Our findings indicate there is both a delay in the onset of the fever and a reduced febrile response in the senescent rats following E. coli infection. PMID- 1624692 TI - The predictive validity of self-report and performance-based measures of function and health. AB - To learn about the value of self-report and performance-based measures of function in predicting mortality and institutionalization, we conducted a longitudinal study of 149 elderly persons at four sites (a senior citizens housing unit, two ambulatory-based geriatrics practices, and a board-and-care facility). At baseline, all subjects were administered a questionnaire containing Katz, Spector, and Rosow-Breslau scale items as well as the Mini-Mental State Exam and two performance-based measures, the Tinetti gait score and Physical Performance Test. At follow-up (average 22 months; range 17-29 months), 17 subjects (11%) had died and seven (5%) had been institutionalized. Univariate analysis demonstrated significant associations between death and all functional status measures. In logistic regression models, Katz items, Tinetti gait score, and the seven-item Physical Performance Test were independent predictors of "death or nursing home placement"; Katz items and the seven-item Physical Performance Test were independent predictors of mortality. These findings support the use of performance-based as well as self-report measures for clinical and research purposes. PMID- 1624693 TI - Opioid analgesics and the risk of hip fracture in the elderly: codeine and propoxyphene. AB - We studied the risk of hip fracture in elderly persons receiving prescriptions for two commonly prescribed opioid analgesics--codeine and propoxyphene. Using automated prescription and hospitalization data, we identified 4,500 residents of Saskatchewan, Canada, aged 65 or older, who sustained a hip fracture between 1977 and 1985, and 24,041 age- and sex-matched controls. Compared to nonusers, the relative risk (95% CI) of hip fracture in current users of codeine or propoxyphene was 1.6 (1.4-1.9). There was no difference between relative risks of fracture among current users of codeine [1.6 (1.3-1.9)] and propoxyphene [1.6 (1.2-2.2)]. In new users of these opioids, the relative risk of fracture was 2.2 (1.7-2.8), compared to 1.3 (1.0-1.6) in users who received at least one additional prescription for codeine or propoxyphene in the 90-day period prior to the index date. Concurrent users of these opioids and psychotropic drugs (sedatives, antidepressants, or antipsychotics) had a risk of fracture 2.6 (2.0 3.4) times that of nonusers of either drug class. Review of a sample of medical records for 701 cases suggested this finding was not due to confounding by body mass, ambulatory status, functional status, or dementia. Given the essential role of opioids in the management of pain in geriatric practice, further study is needed to determine the psychomotor effects of opioid analgesics in older adults. PMID- 1624694 TI - A bowel symptom questionnaire for the elderly. AB - While functional gastrointestinal complaints are common in the elderly, valid instruments for their assessment are lacking. We have developed the elderly bowel symptom questionnaire (EBSQ) and report its feasibility, reliability, and validity in medical outpatients and a larger sample of the community (aged 65 93). Reliability was measured by a test-retest procedure, while concurrent validity was documented by comparing physician interview and self-report data. Reliability (median kappa 0.65, interquartile range 0.49-0.79), and validity (median kappa 0.68, interquartile range 0.51-0.80) were very acceptable. A random sample of 424 independently living elderly persons was obtained; 77% replied to the mail survey. Medical record review showed that no current diagnosis of irritable bowel syndrome was missed by the questionnaire. Our results confirm that the EBSQ was easy to understand and well accepted, and was a reliable and valid measure of gastrointestinal symptoms in older persons; this instrument may have important clinical and research applications. PMID- 1624695 TI - The association of physical activity with mortality among older adults in the Longitudinal Study of Aging (1984-1988). AB - Self-reported physical activity/exercise and mortality among adults aged 70 and over were examined using data drawn from the 1984-1988 Longitudinal Study of Aging (LSOA). Analyses were conducted for the LSOA sample as a whole (N = 5901), for women (n = 3679) and men (n = 2222), and for persons with 1 + IADL difficulties (n = 1592). Results for the whole sample indicated that less activity/exercise was associated with a higher risk of mortality for each of four questions (activity compared to peers, have regular exercise routine, get enough exercise, days walking a mile per week). Analyses by gender indicated that all four questions were important for women, while the two questions asking for a judgment about activity were important for men. For persons with 1 + IADL impairments, walking was associated with lower mortality. This investigation supports literature on the importance of maintaining physical activity into older adulthood, and suggests that clinicians should attend to reports of activity level by their patients as one of the broader psychosocial domains of patient care. PMID- 1624696 TI - Salivary gland function and glucose metabolic status. AB - To study the relationship between glucose metabolic status and salivary gland function in different-aged persons, subjects with diabetes mellitus (DM = 11), impaired glucose tolerance (IGT = 26), and controls (n = 26), aged 24 to 93, were examined in the oral physiology component of the Baltimore Longitudinal Study of Aging. All were generally healthy (except DM) and nonmedicated. The controls and subjects with IGT were classified using World Health Organization criteria, and diabetic status was assessed using Hb1Ac levels. Unstimulated and 2% citrate stimulated parotid and submandibular salivary flow rates were collected, and subjective responses to questions about salivary hypofunction were evaluated. No statistically significant differences were observed between the three groups, nor between young and old subjects with altered glucose metabolism. These findings suggest that among well-controlled individuals with altered glucose metabolism, salivary gland function is not significantly impaired. PMID- 1624697 TI - Exercise training improves fat distribution patterns in 60- to 70-year-old men and women. AB - Changes in body composition and fat distribution in response to endurance exercise training were compared in 47 men and 46 women, aged 60 to 70 yr. Body composition was assessed by hydrodensitometry and fat distribution was evaluated with skinfold thickness and circumference measures. The 9- to 12-mo exercise program consisted primarily of walking and/or jogging for 46 +/- 5 min.d-1, 4.0 +/- 0.6 d.wk-1, at 80 +/- 5% of maximal heart rate. Although men lost more weight during the exercise program than women (men, -3.4 +/- 4.4 kg; women, -1.6 +/- 3.8 kg), relative changes were not significantly different, averaging -3.7 +/- 4.1% and -2.7 +/- 2.9% of body weight in men and women, respectively. The changes in body weight reflected fat loss, as fat-free mass did not change. The reductions in skinfold thickness and circumferences were similar in men and women, and in both groups the largest absolute and relative changes occurred in the truncal area, indicating a preferential loss of fat from the central regions of the body. The results of this study indicate that endurance exercise training can favorably modify the abdominal fat distribution profile that is typical of older men and women in the United States and thus, perhaps, reduce the risk of the diseases associated with abdominal obesity. PMID- 1624698 TI - Rhythmic vs homeostatic influences on mood, activation, and performance in young and old men. AB - Nine healthy old (80+ years) men were compared with nine healthy young (20-30 years) men in a protocol that required 36 hours of continuous wakeful bedrest. Body temperature rhythm measurement confirmed that the old had as robust an endogenous circadian (approximately 24 hours) rhythm generation mechanism as the young. However, in measures of affect, activation, visual search speed, verbal reasoning speed, manual dexterity, and vigilance hit rate, the old showed a linear decline over the 36 hours of the vigil, with little of the superimposed 24 hour rhythmicity that was apparent in the young. Thus, separate from the endogenous rhythm generation processes, there appeared to be some attenuation with advanced age, which led to the relative absence of rhythmic expression in these mood and performance variables. Such attenuation might contribute to some of the sleep and performance problems reported by elderly adults. PMID- 1624699 TI - The factorial generality of brief positive and negative affect measures. AB - Confirmatory factor analysis was used to test the structure of 5-item affect rating scales designed to measure positive affect and negative affect. A proposed circumplex affect structure was the source of scales constructed to represent a cluster of positive terms, including pleasantness and activation; the negative terms represented anxiety, depression, and hostility. The hypothesized simple structured positive and negative trait affect factors, with a moderate correlation between them, were found in all cases. Equivalent structure was confirmed for younger adults, middle-aged, and older adults of good health and above-average education. Although the hypothesized simple-structured positive and negative factors emerged for all other groups, three other tests of factor equivalence failed to be confirmed: trait and state factors in the older adult group were not identical. Factors derived from healthy and frail elders were structurally different. Variability among frail elders and variability over 30 days within the same person, when factored, also showed nonequivalence. Although the scales are extremely useful in assessing affect, comparisons across some subject groups should be made with caution. PMID- 1624700 TI - Indicators of active and passive coping in myocardial infarction victims. AB - This retrospective study attempted to explore life events, personality factors, subjective perceptions, and coping reactions in myocardial infarction (MI) patients. Seventy-seven MI survivors participated in the study. The PERI Life Events Scale, the 16 PF personality inventory, and a questionnaire covering self ratings of subjective perception and coping reactions were used to assess event related influences. The following results were obtained: Multiple regression analyses yielded strong relationships between insecurity predicting perceived changeability, challenge, and threat. The number of prior events was a good predictor for problem solving and self-reflection, while self-attribution for the occurrence of the MI predicted self-blame and denial. A structural equation model indicated that anxiety and experience with stressful events were salient predictors for appraisal, whereas experience with prior events best predicted active coping, and socioeconomic status negatively predicted passive coping. PMID- 1624701 TI - Caregiver and environmental variables related to difficult behaviors in institutionalized, demented elderly persons. AB - This study describes the relationship between caregiver and elder behavior in institutionalized, cognitively impaired, elderly persons. A repeated-measures design was used to observe interactive behaviors between caregivers and demented elders within three caregiving situations (dressing, toileting, and bathing) and an interpersonal contact in two long-term care facilities. During observations, the caregiver's behaviors were rated using the Interaction Behavior Measure and Health Professional's-Geriatric Patient Behavior Rating scale, whereas the elder's behaviors were rated using a modified version of the Interaction Behavior Measure. The study included 116 subjects (58 elders and 58 caregivers), with each unique caregiver/elder pair being observed in the four situations. All elder behaviors varied according to situation type, with the most difficult elder behaviors occurring during bathing. Ten of the 12 caregiver behaviors included in the analysis varied by situation type. Significant relationships were systematically found between the caregiver's relaxed and smiling behavior and the elder's calm/functional behaviors, r = .42 (dressing) to r = .46 (toileting) for caregiver relaxed behavior and r = .34 (bathing) to r = .58 (dressing) for smiling. The elder's behavior did not vary by type of nursing unit (special dementia unit or general nursing unit), or interruptions to the interaction. PMID- 1624702 TI - Influence of direct computer experience on older adults' attitudes toward computers. AB - This research examined whether older adults' attitudes toward computers became more positive as a function of computer experience. The sample comprised 101 community-dwelling older adults aged 57 to 87. The intervention involved a 2-week computer training program in which subjects learned to use a desktop publishing software program. A multidimensional computer attitude measure was used to assess differential attitude change and maintenance of change following training. The results indicated that older adults' computer attitudes are modifiable and that direct computer experience is an effective means of change. Attitude change as a function of training was found for the attitude dimensions targeted by the intervention program: computer comfort and efficacy. In addition, maintenance of attitude change was established for at least two weeks following training. PMID- 1624703 TI - Adults' reading comprehension: effects of syntactic complexity and working memory. AB - Two experiments investigated the relationship between working memory and reading comprehension. In the first, college students, 18 to 26 years of age, and adults, 60 to 92 years of age, were given a battery of tests of working memory, a standard timed reading comprehension test, and a reading test designed to explore how syntactic complexity affects comprehension. In a follow-up study, the adults were retested on a modified version of the syntax comprehension text. Age group declines in working memory and reading comprehension were obtained in Experiment I; age group declines in reading rate but not comprehension were obtained in Experiment II. The results suggest that working memory limitations affect elderly adults' ability to process complex syntactic constructions, lowering comprehension in the timed test (Experiment I) and reducing reading rates in the untimed test (Experiment II). PMID- 1624704 TI - A comparison of changes in macrolinguistic and microlinguistic aspects of discourse production in normal aging. AB - Middle-aged and elderly healthy subjects were interviewed informally, and their discourse productions were analyzed to test for age-related changes in language specific, microlinguistic, and in higher order organizational, macrolinguistic abilities. No significant age differences were found on microlinguistic measures, including syntactic complexity and syntactic and lexical production errors, and there were also no age differences in the use of lexical cohesive ties, such as anaphora. Older subjects, however, obtained significantly lower ratings on a macrolinguistic measure of global thematic coherence. Elderly subjects failed to maintain coherent reference to the general topic of discourse, although they preserved coherent meaning relationships between contiguous utterances. These results are most compatible with the view that age-related performance declines on language tasks primarily reflect changes in macrolinguistic abilities that require integration of linguistic and nonlinguistic cognitive processes, rather than changes in language-specific cognitive processes. PMID- 1624705 TI - Recall of organizable words and objects in adulthood: influences of instructions, retention interval, and retrieval cues. AB - Young (mean age = 27.3 years), young-old (mean age = 66.3 years), old (mean age = 74.8 years), and old-old adults (mean age = 84.0 years) learned organizable words and objects with standard instructions or organizational instructions. Immediate and delayed free recall and delayed cued recall were assessed. Results indicated equal cue benefits for all age groups for words, although cue benefits increased with increasing age for objects. Instructions to organize the items enhanced memory only for the old-old adults. Young adults forgot fewer items from immediate to delayed free recall than the older age groups. In addition, organizational instructions affected word recall, but not object recall, for all age groups. Although these data indicate both similarities and differences in patterns of performance among age groups, the overall pattern of outcome suggests an age-related increase in the level of cognitive support required to optimize episodic remembering. PMID- 1624706 TI - Age-related changes in the effects of target orientation on word recognition. AB - Twenty-four undergraduates and 24 retired faculty participated in an experiment involving semantic priming of lexical decisions. Age-related differences in the use of semantic information during visual word recognition were examined at varying orientations of the target word. Four main results were found: (1) larger rotation effects for elderly adults; (2) larger priming effects for elderly adults; (3) larger priming effects with increasing Target Orientation; and (4) larger priming effects for the elderly adults as Target Orientation increased. Results are interpreted within an interactive-compensatory framework. PMID- 1624707 TI - Age differences in short-term memory: organization or internal noise? AB - Older and young adults' letter search performances were examined on a short-term memory (STM) task where subjects compared a five-letter target sequence stored in short-term memory to a subsequently presented five-letter probe sequence. The same five letters were always presented on target and probe portions of a given trial, but on half of the trials, two letters were transposed in the first chunk, second chunk, or between the first and second chunks of the probe sequence ("No" trials). On the remaining half of the trials, the target and probe sequences were identical ("Yes" trials). Both young and older adults showed increases in reaction time (RT) when the chunk boundary for "yes" trials was different for the target and probe sequences of a given trial. This finding indicated that both age groups were organizing the sequences in STM in the same qualitative manner. However, older adults showed a relatively greater increase in RT and errors than young adults for second-chunk transpositions than for first-chunk or between chunk transpositions, and this finding suggested that an age difference in task complexity could not account for this effect. We propose, though, that these data are consistent with an internal noise model. PMID- 1624708 TI - Criterion validity of the cross-cultural cognitive examination in Japan. AB - Criterion validity of a two-stage Cross-Cultural Cognitive Examination (CCCE) designed for epidemiologic use was evaluated in Japanese subjects by comparison with a physician's DSM-III-R diagnosis of dementia and the Hasegawa Dementia Rating Scale (the standard Japanese instrument similar to the Mini-Mental State Exam). We report on 188 subjects tested in three locations in Japan: Tokyo area, Ise, and Osaka. Subjects ranged in age (50-93 years) and education (1-22 years) and included neurology outpatients, community volunteers, and inpatients. The CCCE was 97.4% specific for dementia, with sensitivity of 88%. The correlation with the Hasegawa scale was significant (r(175) = .8230, p less than .0001). Diagnosis using the CCCE showed good validity when compared with Japanese criteria for dementia. If the instrument could be shown to be reliable and more "culture fair" than the currently available tests, it may be useful in cross cultural epidemiologic studies of dementia. PMID- 1624710 TI - The dynamics of caregiving for a demented elder among black and white families. AB - Caregiving dynamics were studied in a sample of 157 Black caregivers of elders suffering from Alzheimer's disease and other dementias. By comparison with White caregivers (N = 472), there were fewer spouses and more nonspouse-nonchild caregivers among Blacks. With control exercised on background and socioeconomic variables, race differences in caregiving appraisal were found. Blacks showed more favorable scores on indices of traditional caregiving ideology, caregiving as intrusion, caregiving satisfaction, and caregiving burden. Interactions between race and background factors increased explained variance in caregiving appraisal only slightly. A cultural explanation of the more favorable appraisals of Blacks was sought in the caregiving ideology factor, but this dimension was not associated with caregiving outcomes. The overall hypothesized two-factor model was generally consistent with the observed covariance structures of both Black and White caregivers. Within both White and Black groups, caregivers who provided more care showed simultaneously more satisfaction and more burden. PMID- 1624709 TI - Memories of parental favoritism and the quality of parent-child ties in adulthood. AB - In order to better understand which factors contribute to variations in the quality of adult child-parent bonds, this study considered parental unfairness in the treatment of offspring during childhood. Using social exchange, self-esteem maintenance, and socialization models to predict different outcomes, memories of least favored status (LFS) were examined in relation to affectional intergenerational solidarity. A secondary analysis of a Swedish data set was conducted. Parent-child dyads were studied within three-generational lineages consisting of a grandmother (G1), her adult child (G2), and the grandchild (G3). Comparing parents and children, ratings of LFS were more predictive of the quality of the bond for children. Comparing generations of parents, LFS memories were more predictive for G2 than for G1. Comparing generations of children, there were no differences. The uniqueness of older parents in family research is considered, and an agenda for future research is suggested. PMID- 1624711 TI - Violence and violent feelings: what causes them among family caregivers? AB - We present a conceptual framework for understanding two distinct but related phenomena: violent feelings (i.e., the fear of becoming violent) and violent behaviors by family caregivers toward relatives with dementia. Based on both the literature on family caregiving and on family violence, four factors are hypothesized to explain these two dimensions of violence: caregiving demands, interactional stressors, caregiver characteristics, and caregiving context. Analyses of quantitative and qualitative data on 236 family caregivers to dementia victims revealed several characteristics that were predictive of violent feelings on the part of caregivers, including physical aggression by the care recipient, disruptive behaviors, and a shared living situation. Structural relationship and caregiver's age were found to be related to actual violence; spouses were more likely to engage in violence than other relatives, as were older individuals. In addition, violence by the care recipient was positively related to caregiver violence. PMID- 1624712 TI - The risk of nursing home placement and subsequent death among older adults. AB - This article examines the effects of the characteristics specified in the behavioral model of health services utilization and measured at baseline on the subsequent risk of nursing home placement and death within four years. Analyses of the 5,151 respondents in the Longitudinal Study on Aging indicate that the risk for nursing home placement is greater for older adults, Whites, those who lived alone, persons with telephones, those with fewer nonkin social supports, those who did not feel that they had much control over their future health, those with more household ADL or lower body limitations, and those who had been in the hospital during the year prior to baseline, or in a nursing home at any time before baseline. Among the 549 respondents placed in nursing homes, the risk of dying there was greater for older adults, men, those who had not lived in multigenerational households, persons who did not worry about their health, individuals with more upper body limitations, and respondents having a history of valvular heart disease or cancer. The odds of dying were 2.74 times greater among the 549 respondents placed in nursing homes than among the 4,602 respondents who remained in the community. PMID- 1624713 TI - Social networks, institutionalization, and mortality among elderly people in the United States. AB - This study focuses on the effect of social networks on institutionalization and mortality among elderly people in the United States. Data are from the Longitudinal Study of Aging (LSOA), which incorporates a baseline interview in 1984 and a follow-up interview two years later. The study population consists of a sample of 5,151 noninstitutionalized elderly people who were 70 years of age or older in 1984. Multivariate analyses using logistic regression revealed that social networks are negatively related to the likelihood of institutionalization and mortality when controlling for sociodemographic characteristics and baseline health status. Elderly people who participated in some form of social activity decreased their risk of institutionalization by almost one-half, whereas living alone increased the likelihood of institutionalization. Participating in social activities and visiting or talking with friends or relatives was negatively related to the likelihood of mortality. PMID- 1624714 TI - Gender differences in exposure to life events and adaptation to retirement. AB - Gender differences in the experience of life events surrounding the retirement transition and the effects of such life event experiences on men's and women's adaptation to retirement were investigated. Data based on a stratified random sample of retirees covered by Florida's State Retirement System (n = 452 women and 378 men) indicate that women report more life events than men, particularly during the period preceding retirement. Furthermore, women's retirement adaptation seems more affected than men's by the experience of life events. The major conclusion to be drawn from these results is that better understanding of gender differences in the retirement experience can be achieved only if gender variations in the circumstances of the retirement transition are acknowledged and further explored. PMID- 1624715 TI - Take the money and sun: elderly migration as a consequence of gains in unaffordable housing markets. AB - We tested the hypothesis that elderly migration, both seasonal and permanent, to Sunbelt states such as Arizona is the result, in part, of economic gains made in unaffordable housing markets. The results of a multiple regression analysis of interstate migration flows to Arizona support the hypothesis. Moreover, the stronger relationship for seasonal migration suggests that elderly households are unwilling to realize housing gains in unaffordable markets but, nevertheless, "spend" the gains on seasonal migration. Such behavior is rational if housing is viewed as an investment and expectations of future returns are greater in unaffordable markets. Given that the study was based on housing gains of the 1970s, the results suggest that more recent elderly migration may be even more influenced by such gains, inasmuch as regional differences in housing affordability have become more pronounced. PMID- 1624716 TI - Quality of self-report data: a comparison of older and younger chronically ill patients. AB - This study examined age differences in the quality of self-report data in patients with chronic disease conditions (hypertension, diabetes, heart disease, depression). Data are from 2,304 patients in three health care systems in Los Angeles, Chicago, and Boston. Results support the idea that self-report health data can be gathered from older and younger patients without significant decrements in data quality. Specifically, results showed: (1) small decreases in the reliability of multi-item measures with age, primarily occurring in balanced scales; (2) little evidence of differences among age groups in response set or the tendency to respond "don't know" or "uncertain," although older patients had a greater tendency to respond in a socially desirable manner; (3) higher item nonresponse in older patients; (4) little variation in item nonresponse by type of question or question placement; (5) generally high panel retention in all age groups, supporting the value of repeated follow-up; and (6) similar known-groups validity across age groups. PMID- 1624717 TI - [Training of the gynecologist-oncologist: the American experience]. PMID- 1624718 TI - [Evaluation of a public health measure for the amelioration of birth safety in Martinique: 1977-1984]. AB - A public health programme was instituted on the island of Martinique (in the Carribean archipelago) between 1977 and 1984. Its aim was to reduce the perinatal death rate in Martinique which was 25.7 per thousand in 1977 to the level found in France in the same year, namely 14 per thousand. The measures taken to improve the safety of deliveries included closing small maternity homes and improving the hospitals both public and private. The chief measure however, was to improve the availability of specialised antenatal care chiefly administered by midwives (free care consultations near the homes) for the poor and the less well educated women. The results showed that perinatal deaths in the island dropped to 14.9 per thousand in 1984. The major improvement was that women who had been attended by midwives had 10 per thousand perinatal deaths. This involved half the population of the island and the same results were found as to the wealthier and more educated women who were attended by private obstetricians. It was found to be possible to reduce the difference in the perinatal death rate between an African population in Martinique and an European population in European France. PMID- 1624719 TI - [Biological reference values in the human fetus. 106 cord blood sampling in utero]. AB - The authors give biological reference figures obtained from 106 fetuses that were sampled in utero between the 20th and 34th week of amenorrhoea. These fetuses were considered to be normal because there was no clinical or ultrasound evidence of an abnormality. Furthermore the biological values sought in antenatal testing and the absence of all pathology in the first year of life, confirmed that these were normal fetuses. The result has been expressed as a global figure for all 106 fetuses; then they have been divided up according to the gestational age groups (20-23, 24-27, and 28-34 weeks of amenorrhoea). These biological reference values and their changes as the age of the fetuses advanced are discussed and compared with the figures reported in the literature. PMID- 1624720 TI - [Microalbuminuria and pregnancy. Is microalbuminuria predictive of pregnancy toxemia?]. AB - Several authors have suggested that estimating the levels of microalbuminuria will help in early screening for pre-eclampsia. The purpose of this work has been to look for the absence of microalbuminuria in normal pregnancies and to work out its predictive value for the risk of toxaemia of pregnancy when it does appear. The study was carried out on 257 women of whom 43 were controls and 214 women who were pregnant and had neither diabetes nor hypertension and had no kidney infections. The samples of urine were gathered in a 12 hour period of night and those that gave a positive reaction for albumin were rejected. RIA techniques were used to work out the levels of albuminuria and these were confirmed by immunoassay. We have compared microalbuminuria, the relationship between urine albumin and creatinine and the clearance of albumin in relationship to albuminuria (as defined by the relationship of albumin and creatinine clearance). We have calculated the sensitivity and the specificity and the prognostic value both positive and negative for these four parameters. Our results show that in a normal pregnancy there should not be any microalbuminuria, and on the other hand that if microalbuminuria does appear according to the four parameters studied, they are all equally sensitive for predicting pre-eclampsia. The relative clearance of albumin from the urine seems to be the most interesting parameter as far as we are concerned, and it could lead to early screening for toxaemia. PMID- 1624721 TI - [Contribution of magnesium gluconate in intravenous tocolysis with ritodrine]. AB - The purpose of this randomized study was to compare the efficacy of ritodrine alone (51) versus ritodrine plus magnesium gluconate (56). We concluded that high oral doses of magnesium therapy (4 x 3 gr) potentiate the effects of intravenous beta-agonists, allowing a reduction of the dosage needed and a better "tolerance". Considering the low side effects, it seems reasonable to consider using magnesium in the treatment of premature labour. PMID- 1624722 TI - [Protocol of cervical maturation by acupuncture]. AB - Protocol was carried out on 98 patients who were divided into three groups selected as (one control group, two "placebo" group, and three treated with acupuncture). This protocol showed that it was possible to improve cervical maturation if acupuncture sessions were carried out at the beginning of the 9th month. The Bishop scores in the three groups after 10 days interval show that there was a significant progression of 2.61 points in the group treated with acupuncture as against only 0.89 and 1.08 in the placebo and control groups. PMID- 1624723 TI - [Disseminated lupus erythematosus discovered during delivery: a difficult diagnosis]. AB - The authors report a case of lupus showed in labour by the presence of generalised convulsions and coma after the crisis. This was followed by labile transitory hypertension, by massive proteinuria which cleared in 15 days, by major hyperthermia (higher than 39.5 degrees) and transitory agranulocytosis. The infant had a purely biological neonatal lupus. Pregnancy in a lupus patient has two risks: the mother's relapses of lupus, it is usual that renal failure is the worst of the prognostic features, but in this patient cerebral complications were much more serious. In the fetus there is a risk of spontaneous abortion linked to the anticardiolipin antibody level, and the risk of disease in the heart due to the anti-SSA (or anti-Ro) factor giving rise to congenital auriculo-ventricular blocks. The therapeutic possibilities are classically treated with immunosuppressants, mainly corticoids, which is added to low doses of aspirin. Plasmaphoresis and immunoglobulin treatments are being tried out. PMID- 1624724 TI - [Mycoplasmas and pregnancy. Preliminary study]. AB - The prevalence of genital mycoplasmas was studied among 191 pregnant women followed up at Diaconesses Hospital, Paris. Ureaplasma urealyticum was recovered from 65% of patients, alone (54%) or in association with Mycoplasma hominis (11%). The relationship to pregnancy outcome, the effect of erythromycin treatment, the interest of biological markers of infection (mycoplasmal quantitation and serologic tests, C-reactive protein) and the role of other known genital pathogens were investigated. Vaginal infection with Ureaplasma urealyticum according to biological criteria (i.e. vaginal concentration greater than 10(3) CCU/ml or coisolation of Mycoplasma hominis) was significantly associated with an increased risk of: 1. premature rupture of the fetal membranes; 2. prematurity in cases of preterm labor. Erythromycin treatment was able to prevent only the risk of prematurity. On the other hand, we didn't show any influence of mycoplasmal colonization on birth weight, if expressed with regard to gestational age. An immune response to Ureaplasma urealyticum was demonstrated in 15% of patients; rare fourfold antibody rises were detected specially in the case of a second trimester spontaneous abortion and of an intrauterine death (both were untreated patients) and probably attest an infectious process. A randomized trial with a larger study sample must be undertaken to corroborate these preliminary data. PMID- 1624725 TI - [Bacterial infection of the newborn by maternal fetal contamination: one can depend on the anamnesis]. AB - All babies born in a University maternity unit over a period of four months had bacteriological swabs taken in the labour ward. This was to see whether a list of criteria in the history for bacterial infection of the newborn could be relied on. The criteria were: premature rupture of the membranes (before labour had started at all), rupture of the membranes for more than 12 hours, stained liquor, prematurity, fetal tachycardia of more than 160 per minute or abnormal rhythm of the heartbeat, an Apgar score of less than 7 after 1 minute, maternal genital or urinary tract infection (not cured) in month before delivery, maternal temperature above 38 degrees C in labour. During the study there were: 570 live births of which 222 (39%) were at risk of infection according to the above list of criteria, 35 had bacterial colonies present and 4 were definitely infected. More cultures from the placenta, the gastric fluid and the skin came back positive when there was a recognised risk of infection. Both the clinical and bacteriological results show that the risk was 5.24 of colonisation when the risk of infection had been recognised. These prospective results when checked against the retrospective results already obtained in the same department, suggest that this kind of screening for infection is worthwhile without being too expensive, and one can rely on the history to screen for neonatal bacterial infection. PMID- 1624726 TI - [Weight and length of newborns. Differences between boys and girls]. AB - Examination of 8,312 deliveries shows that the difference in weight between boys and girls at birth can be explained completely by the difference in their length. The sex of the child has no influence on the length of the pregnancy. This is influenced by the birth order, the propensity to smoke (tobacco), the mother's weight gain in pregnancy and her social level. The speed of intrauterine growth is influenced by the sex of the fetus, the number of pregnancies she has had, by tobacco, and by the amount of education she has had and her weight gain in pregnancy. PMID- 1624727 TI - [Esthetic results of breast reconstruction after amputation for cancer. 323 cases]. AB - 323 reconstructions of the breast were carried out at the Gustave-Roussy Institute and were analysed in order to assess the aesthetic results and the sequelae of these reconstruction operations. The majority of the patients were operated on between 1984 and 1989 with a median follow-up of 3.5 years (1 to 9 years). Three types of reconstruction were carried out: simple prosthesis behind the muscle (P, 69% of this population), latissimus dorsi flap (G.D., 11%), or transverse rectus abdominis flap (TRAM, 20%). These reconstructions were either carried out immediately (RMI, 23.5%) or later (RMD, 76.5%). The unanimous enthusiasm of the patients for reconstruction was the greatest encouragement for us to continue in this way. From the aesthetic point of view the transverse rectus abdominis flap (TRAM) proved to be superior to the others. Scar and functional sequelae of the latissimus dorsi flap (GD) were by no means nil in this series (table 9) in contrast with other studies that have been carried out. All the same the majority of these sequelae were larger scars. The functional poor sequelae were minor. TRAM sequelae were less frequent and usually mainly in the abdominal wall. A more accurate technique should lower the incidence. As far as the timing of surgery is concerned, immediate reconstruction did not alter the quality of results which were better (but not significantly statistically). This has already been published. On the other hand patients were more satisfied with RMD (p less than 10(-4)). The analysis of this unexpected result show the great significance of psychological factors in interpreting these results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1624728 TI - [Chromosome X with partial long arm deletion. Three cases]. AB - X deletions result generally in one or many features characteristic of Turner syndrome but each feature cannot be attribute to a well defined deletion. We present 3 cases of Xq partial deletion: 2 in girls with primary amenorrhea and normal stature, 1 in a patient with secondary amenorrhea and short stature. X inactivation is a complex phenomenon, the mechanism is not yet clear. Inactivation center(s) and active genes on inactive chromosome could explain the manifestation or the absence of clinical symptoms in X deletions. PMID- 1624729 TI - [The combined stimulation test sulpiride-TRH in the investigation of prolactin secretion]. AB - We have studied the response of prolactin (PRL) secretion to the test combining i.m. sulpiride in the dose 1 mg/kg followed by 200 micrograms i.v. of TRH, in 12 normal women and 37 patients with hyperprolactinaemia. The response was expressed as a percentage rise in plasma PRL concentration (delta %) 20 minutes after the administration of sulpiride or TRH. In the controls the response in PRL secretion to sulpiride worked out at between 639 and 2,760%. When there was a pituitary adenoma or supra-sellar lesion the PRL response to sulpiride was always less than 481%. On the other hand the PRL response with TRH after sulpiride was not significantly different as between the controls (less than 175%) and the patients (less than 91%). We conclude: 1) the combined sulpiride and TRH test is useless for assessing hyperprolactinaemia; 2) the sulpiride test on the other hand makes it possible to show that hyperprolactinaemia cannot be stimulated and to suspect the presence in this case of a prolactin producing adenoma or a supra-sellar tumour. PMID- 1624730 TI - [Hypertrophic tuberculosis of the cervix. Three cases]. AB - Tuberculosis of the cervix of the uterus is a rare form of genital tuberculosis. The epidemiology does not have any particular specific feature; but the macroscopic appearance gives a first impression of a cancer. Only by carrying out a biopsy of the cervix, followed by study of the histology can the problem be solved so that longterm anti-tuberculous treatment can be started. There is rarely any need for surgery, that only in cases resistant to medical treatment. The authors report three cases of tuberculosis of uterine cervix, found in the university clinic of obstetrics and gynaecology I (Professor Chaoui) during the years 1986-90. The incidence of this condition is 8.5% of genital tuberculosis. The outlook is good with full healing if the treatment is carried out properly. PMID- 1624731 TI - [Ovarian struma: 2 cases]. AB - The authors report two cases of ovarian goiters; they insist upon their rarity and the difficulty of their pre-operatory diagnosis. Only histologic examination can affirm their goitrous origin. The treatment of ovarian goiters is surgical. The evolution is favorable except their exceptional malignant transformation. PMID- 1624732 TI - [Endometrial ablation by fiberoptic hysteroscopy and YAG laser]. AB - The authors report the first cases of the use of operating fibre hysteroscopes with YAG laser to carry out endometrial ablation. Fiberoptic hysteroscopes were used and made it possible to carry out the procedure with much greater precision because of their mobility and flexibility. YAG laser rays are passed down an operating channel and can treat the whole of the endometrium in 20 minutes operating time. This treatment was suggested to 44 patients who had menorrhagia and did not respond to treatment with progestogens as an alternative to hysterectomy. There were 81.7% very good results, 11.3% good results and only 7% failures with a followup period of 3 to 20 months. There was no operative or post operative complication either in the short or the longterm. This technique is a new one and not much used in France, but its advantages have been confirmed by several authors, especially in the United States. PMID- 1624733 TI - [Renal toxicity of intraperitoneal cisplatin: a case report]. AB - The new technique of treating ovarian tumours by giving cisplatin intra peritoneally does have its risks. This case history reports the case of a patient who was treated in this way and following the treatment had renal failure severe enough to require dialyses. The methods of administering cisplatin through this route have not yet been worked out completely. It is absolutely to over hydrate the patient beforehand. PMID- 1624734 TI - [Techniques too advanced (or poorly advanced) in laparoscopy or hysteroscopy? Reflections of an uneasy judicial expert]. PMID- 1624735 TI - [infectious spondylodiscitis after genital prolapse cure]. PMID- 1624736 TI - Abdominal compressions during CPR: hemodynamic effects of altering timing and force. AB - To determine the optimal method of applying abdominal compressions during cardiopulmonary resuscitation (CPR), 3 levels of pressure (25, 50, and 100 torr) were applied to the abdomen a) continuously and b) as 500 msec pulses at 10 different phases during the CPR cycle in 8 anesthetized dogs. Thoracic aortic (Ao) and right atrial (RA) pressures were measured and PAo-PRA was calculated as the coronary perfusion gradient. A pneumatic piston device provided external chest compression (60/min, 120 lbs, for 50% of the cycle) and ventilation (80% O2, 12/min, at 20cm, H2O). Another identical device provided abdominal compression (AC) via an air-filled bladder. High-pressure (100 torr) AC applied for 500 msec commencing 200 msec prior to chest compression demonstrated the best overall profile, raising mean aortic pressure 26 torr (P less than 0.001) and peak coronary perfusion gradient pressure 17 torr (P less than 0.02) from control values during standard CPR of 58 and 41 torr, respectively. We conclude that applying high-pressure, 500-msec pulses of AC 200 msec before chest compressions significantly improves CPR hemodynamics. PMID- 1624737 TI - Clinical indicators of dehydration severity in elderly patients. AB - STUDY OBJECTIVE: To determine which of the signs and symptoms of dehydration obtainable from patient history and physical examination in the emergency department are most useful in assessing the severity of dehydration in elderly patients. DESIGN: Prospective, correlational study. SETTING: Two university teaching hospitals. PATIENTS: Fifty-five patients aged 60 or older presenting to the emergency department with suspected dehydration were studied. MEASUREMENTS AND MAIN RESULTS: In the emergency department, patients were evaluated by a standardized history and physical examination that included assessment of 38 signs and symptoms commonly attributed to dehydration. The relationships between the presence and intensity of these putative dehydration indicators and an independent rating of dehydration severity based on a comprehensive review of the medical record were evaluated. Also evaluated were the relationships between these dehydration indicators and patient age. Indicators that correlated best with dehydration severity but were unrelated to patient age included: tongue dryness (P less than 0.001), longitudinal tongue furrows (P less than 0.001), dryness of the mucous membranes of the mouth (P less than 0.001), upper body muscle weakness (P less than 0.001), confusion (P less than 0.001), speech difficulty (P less than 0.01), and sunkenness of eyes (P less than 0.01). Other indicators had only weak associations with dehydration severity or were also related to age. Patient thirst was unrelated to dehydration severity. CONCLUSIONS: A set of signs and symptoms related to dehydration severity in elderly patients has been identified. These indicators may be more useful for evaluation of dehydration severity in the emergency department than other commonly used indicators. PMID- 1624738 TI - A comparison of diagnostic peritoneal lavage and computed tomography (CT scan) in evaluation of the hemodynamically stable patient with blunt abdominal trauma. AB - The diagnosis of intraabdominal injury in the patient who is victim of blunt trauma is often problematic. Currently, two procedures, diagnostic peritoneal lavage (DPL) and computed tomography (CT scan) are used to evaluate patients with possible intraabdominal injuries after blunt trauma. Controversy exists as to which of these modalities is more efficacious in this setting. There are advantages and disadvantages of both procedures, however, present evidence suggests that the clinician should not rely on the results of the CT scan. The DPL, on the other hand is a sensitive and specific modality in evaluating the patient with blunt abdominal trauma. PMID- 1624739 TI - Functional urinary outlet obstruction causing urosepsis in a male multiple sclerosis patient. AB - Detrusor-external sphincter dyssynergia (DESD) is a neuropathic disorder of micturition that exists when the simultaneous contractions of the detrusor muscle and external urethral sphincter oppose each other. When the external urethral sphincter contracts during a detrusor contraction, functional urinary outflow obstruction occurs by the increased urethral resistance. This loss of coordination between the bladder and its outlet is associated with a high risk for serious urologic complications, such as vesicoureteral reflux, hydronephrosis, and urosepsis. This report describes a male multiple sclerosis patient with DESD who developed functional outlet obstruction with urosepsis and discusses the diagnosis and treatment of this potentially life-threatening voiding dysfunction. PMID- 1624740 TI - Scavenging high-voltage copper wire, a hazardous petty larceny. AB - With the current emphasis on recycling and the establishment of markets for sale of used copper wire, scavenging of copper wire from old buildings and equipment has become common. Although scavenging without permission constitutes theft, a more significant risk to the perpetrator is the potential for electrical burn injury in attempting to remove "hot" wire. A severe high-voltage electrical burn injury sustained while attempting to scavenge wire from an old house is reported. The circumstances surrounding the injury, the clinical management of the case, and the long-term consequences to the patient are presented and discussed. PMID- 1624741 TI - The use of cough-CPR in patients with acute myocardial infarction. AB - A case of a patient with an acute anterior myocardial infarction (MI) and ventricular fibrillation is presented. The patient was resuscitated after cough cardiopulmonary resuscitation (C-CPR) was administered in the emergency department. The patient received thrombolytic therapy without complication. Cough CPR is a technique not in widespread use. With the advent of thrombolytic therapy for patients with acute myocardial infarctions, a relative contraindication to thrombolytic therapy is present in patients who receive "standard CPR." The use of cough-CPR in witnessed dysrhythmias can alleviate this problem. Cough-CPR can also reduce the morbidity of resuscitations. PMID- 1624743 TI - Dual AV nodal paths leading to AV nodal reentrant tachycardia. AB - A 27-year-old white female with a history of paroxysmal supraventricular tachycardia presented to the emergency department complaining of intermittent palpitations. Although no tachydysrhythmia was present, she was noted to have two distinct PR intervals during normal sinus rhythm while in the emergency department. The patient was referred for electrophysiologic study. This study demonstrated dual AV nodal paths, and AV nodal reentrant tachycardia was induced and terminated. She was placed on flecainide for outpatient management of her dysrhythmia. Dual AV nodal pathways leading to AV nodal reentrant tachycardia is discussed. PMID- 1624742 TI - Cinchonism: two case reports and review of acute quinine toxicity and treatment. AB - Two cases of acute quinine toxicity are presented, one from self-poisoning and the other from an unidentified source. Both patients presented with acute bilateral blindness. They also experienced the classic symptoms of cinchonism, including nausea, vomiting, and tinnitus. Prolongation of the Q-T interval developed in both patients. Serum quinine levels of 5.3 mg/L and 13 mg/L were measured. Although their visual acuity improved, both patients had some residual deficit at follow-up. A review of the literature, including clinical presentation and emergency medicine diagnosis and management, is also presented. PMID- 1624744 TI - Influence of emergency physician's tying technique on knot security. AB - The purpose of this study was to determine the influence of emergency physician's tying technique on knot security using 2-0 and 4-0 monofilament and multifilament nylon sutures. Using an Instron Tensile Tester and a portable tensiometer, knot security was achieved with these sutures using four-throw square knots (1 = 1 = 1 = 1). After didactic and psychomotor skill training, medical students were taught to construct the four-throw square knot using either a two-hand tie or an instrument tie. Using the portable tensiometer, their knot tying techniques were judged to be superior to those used by emergency physicians. The emergency physician's faulty technique can easily be corrected by didactic information and psychomotor skill training. PMID- 1624745 TI - Emergency department evaluation and management of dialysis patient complications. AB - The number of dialysis patients in the United States has markedly increased in recent years to more than 100,000. An emergency physician is increasingly likely to be presented with the challenge of handling the emergent problems of the dialysis patient. This article is a review of the complications seen in the population of hemodialysis and peritoneal dialysis patients, with recommendations for emergency department evaluation and management. PMID- 1624746 TI - Suicide: risk factors and therapeutic considerations in the emergency department. AB - Emergency physicians often encounter covertly and overtly suicidal patients, and can thus play a key role in the prevention of suicide. The epidemiology and diverse presentations of suicidal behavior are reviewed. We then provide a detailed approach to the assessment of suicide risk, and criteria for safe discharge from the emergency department (ED). Finally, management considerations for the ED are discussed. PMID- 1624747 TI - The efficacy and safety of tissue plasminogen activator in acute ischemic strokes. AB - Over the past decade there has been an increasing use of thrombolytic agents in the treatment of coronary artery disease, pulmonary embolism, and thromboembolic strokes. The use of thrombolytic agents has been most successful in treating acute myocardial infarction. When treatment with intravenous streptokinase or tissue plasminogen activator (tPA) is initiated within the first 3 to 4 hours from the onset of symptoms, the rate of reperfusion ranges from 60% to 90%, as compared to a rate of 13% to 21% for placebo control. Both streptokinase and tPA have been extensively studied as therapies for acute myocardial infarction, and in general, a higher initial rate of reperfusion is achieved in tPA-treated patients than in streptokinase-treated patients, although the final arterial patency rate may not be different in the two groups due to a higher rate of reocclusion in the tPA-treated population. Furthermore, time dependency for efficacy from the onset of symptoms to the initiation of treatment is less for tPA than for streptokinase. However, the role of thrombolytic agents in the treatment of thromboembolic strokes is more experimental than clinical at the present time. Of all agents, tPA is the most promising and the most extensively studied. This paper will review the experimental data on the use of tPA in acute thromboembolic strokes as well as the existing clinical data on stroke reperfusion. PMID- 1624749 TI - Yet another ACLS!--(advanced "conference" life support) PMID- 1624748 TI - Intravenous adenosine in the treatment of junctional tachycardia. PMID- 1624750 TI - Objectives to direct the training of emergency medicine off-service rotations: anesthesiology. AB - This is the 15th article in a continuing series of "off-service" goals and objectives for resident education in emergency medicine. Knowledge and skills in providing anesthesia and analgesia are essential in managing patients in the emergency department, critical care unit, and surgery. However, Anesthesiology off-service rotations are often limited to a 2-week rotation. Therefore, clear goals and objectives in Anesthesiology are essential for the resident in training. PMID- 1624751 TI - Fast Track in the emergency department: a one-year experience with nurse practitioners. AB - The use of a Fast Track system in the emergency department is becoming increasingly popular in order to provide fast and efficient service to patients with minor emergencies. In this paper we describe the one-year results of our system staffed by nurse practitioners. During the first year of operation, a total of 4468 patients were seen in Fast Track. Approximately 28% of patients are triaged to Fast Track during its hours of operation. The average patient seen in Fast Track was ready for discharge 94.4 minutes after presentation. Fewer than 1% of patients required admission to the hospital. Overall, patients and medical staff were highly satisfied with the Fast Track system. Our experience demonstrates that nurse practitioners can effectively and efficiently staff a Fast Track in an academic emergency department. PMID- 1624752 TI - Intensive care. PMID- 1624753 TI - Sub-types of serotonin receptors: biochemical changes and pharmacological consequences. AB - Thirty-three years ago, Gaddum and Picarelli classified the serotonin receptors in the guinea pig ileum into D and M types based on the activity of dibenzyline and morphine to block contractions of intestinal smooth muscle caused by serotonin. The subsequent location of specific ligand binding sites for serotonin in the brain has led to the identification of at least eight serotonin receptor sub-types in rat brain. While there is some controversy over the functional importance of many of these receptor sub-types, there is evidence that they fall into two major groups according to the nature of their coupling to secondary messengers or ion channels. Thus the 5-HT1 and 5-HT2 receptors appear to occupy the G protein receptor sub-family which may be coupled either to adenylate cyclase (most 5-HT1 sub-types) or phosphatidyl inositol (5-HT2 sub-types). The central "M" receptors (now termed 5-HT3) appear to occupy a ligand gated ion channel super-family. The cloning of three of the serotonin receptor sub-types in 1989 (5-HT1A, 5-HT1C and 5-HT2) has been of importance in enabling the receptor sub-types to be classified as specific protein molecules encoded by specific genes. The problem now arises with regard to the linking of the changes in the cellular activity of the various receptor sub-types with the plethora of behavioural changes that arise as a consequence of the actions of serotonin in the brain. The present review summarizes the evidence implicating the role of specific serotonin receptor sub-types in eating disorders, sleep, sexual activity, anxiety states, aggression, schizophrenia and depression. A summary of the relationship between these receptor sub-types and their possible involvement in the aetiology of these diseases is shown in Table 2. PMID- 1624754 TI - Pharmacokinetics of tetrahydroaminoacridine: relations to clinical and biochemical effects in Alzheimer patients. AB - The pharmacokinetics of tetrahydroaminoacridine (THA) was studied in patients suffering from Alzheimer's dementia. Single doses of the drug were administered by intravenous (15 mg), oral (50 mg) and rectal routes (25 mg). Pharmacokinetic parameters were related to clinical and biochemical effects in patients who, in a separate study, participated in a clinical trial of oral THA. The bioavailability of THA was low and varied considerably between subjects. Clinical improvement and occurrence of elevated liver enzymes correlated positively with drug bioavailability. Acetyl and butyryl cholinesterase activities in the plasma did not change following THA administration. Rectally administered THA had a higher bioavailability than orally administered THA in three subjects who were given the drug by both routes. These results indicate that a clinical trial of rectal THA would be justified as this administration route may improve resorption and diminish first-pass metabolism of the drug in the liver compared with oral administration. PMID- 1624755 TI - Impulsive aggression and central serotonergic system function in humans: an example of a dimensional brain-behavior relationship. AB - A dimensional relationship between central serotonergic (5-HT) system function and indices of suicidal and impulsive aggressive behaviors has been suggested by more than a decade of research in patients with psychiatric disorders. This paper reviews a series of studies conducted in healthy male individuals and in male patients with major mood and/or personality disorder involving pharmacochallenge and neurochemical strategies designed to explore the role of central 5-HT system function in the regulation of suicidal and impulsive aggressive behavior in humans. The results of these studies suggest that reduced overall central 5-HT function in the limbic-hypothalamic system is associated with suicidal and/or impulsive aggressive behaviors in patients with major mood and/or personality disorders and that diminished 5-HT post-synaptic receptor function in this brain region may be an important biological correlate of these behaviors. PMID- 1624756 TI - Buspirone induced prolactin responses in obsessive-compulsive disorder (OCD): is OCD a 5-HT2 receptor disorder? AB - Buspirone (BUSP) is a serotonergic (5-HT) agonist with activity at the 5-HT1A receptor. The BUSP induced prolactin (PRL) response was examined in 10 patients with a DSM IIIR diagnosis of obsessive-compulsive disorder (OCD). The results were compared with PRL responses to BUSP found in 10 age and sex matched healthy controls. The results suggest that the 5-HT1A receptor dysfunction may not be involved in the pathophysiology of OCD. The authors review the literature and consider the hypothesis that in OCD a complex interaction of other 5-HT receptor sub-types may be occurring, possibly with dysfunction primarily of the 5-HT2 receptors. PMID- 1624757 TI - The effects of lithium on body weight and food intake in normal subjects--a pilot study. AB - The possibility of lithium increasing hunger and food intake was examined in an open, pilot study involving five healthy male volunteers each of whom took lithium for 1 month at a dose to give mean 12 h serum lithium level of 0.5-0.8 mmol/l. Before starting lithium, after the first dose and again after 1 and 4 weeks on lithium, subjects attended the unit at lunch time. They were starting lithium, after the first dose and again after 1 and 4 weeks on lithium, subjects attended the unit at lunch time. They were weighed and ate their lunch time meal from a food dispenser similar to those in canteens. Subjective rating scales were completed before and after eating. No change in weight was seen. Food intake was slightly increased at the end of the month on lithium compared with the start but had fluctuated during the intervening weeks. There was no relationship between food intake and weight change. PMID- 1624758 TI - Treatment resistant depression in the elderly: three cases. AB - We report three cases of severe depression in whom ECT was relatively contraindicated, who responded dramatically to switching lithium and fluoxetine to lithium and lofepramine. Possible mechanisms are discussed. PMID- 1624759 TI - Alcohol-free beer and the irreversible monoamine oxidase inhibitors. AB - Three cases of vascular crises associated with the use of MAOIs and the ingestion of alcohol-free beer are reported. PMID- 1624760 TI - Profiles in genetics: J. B. S. Haldane (1892-1964)--a centennial appreciation. PMID- 1624761 TI - An advantage of sexual reproduction in a rapidly changing environment. AB - When an environmental change imposes strong directional selection, there are two advantages of sexual reproduction. First, an asexual population is limited to the most extreme individual in the population, and progress under directional selection can go no farther without mutation; no such limitation applies to a sexual population. Second, more quantitatively, directional selection in an asexual population monotonically decreases the variance, whereas the variance of a sexual population quickly reaches a steady value; this difference remains even if the direction of selection occasionally changes. With realistic environmental changes small alterations in any particular measurement or trait are usually sufficient to keep up with the changes, but fitness, since it depends on a large number of traits, will be selected with greater intensity, which may be enough to confer a distinct advantage on sexual reproduction. This applies particularly to a large or rapid environmental change. Eventually mutation will enhance the variance, but by then it may be too late to prevent extinction of asexual strains. PMID- 1624762 TI - The molecular taxonomy and evolution of the guinea pig. AB - On the basis of 18 protein sequences totaling 2,413 aligned amino acid sites, it is suggested that the guinea pigs and the myomorphs (rat-like rodents) are not monophyletic. Rather, the evolutionary lineage leading to the guinea pig seems to have branched off prior to the divergence among myomorphs, lagomorphs, primates, chiropterans, artiodactyls, and carnivores. It is suggested therefore that the Caviomorpha (guinea pig-like rodents) and possibly the Hystricomorpha (porcupine like rodents) should be elevated in taxonomic rank and conferred an ordinal status distinct from the Rodentia. This suggestion calls for a reevaluation of the morphological evolution of guinea pigs and further molecular studies on the possibility of paraphyly of the order Rodentia. If the monophyly of rodents holds, it must be concluded that the pattern of molecular evolution in many guinea pig genes has been extremely unusual and that the causes for this pattern should be sought. It is also suggested that claims of large differences in the rate of molecular evolution between guinea pigs and myomorphs may have been exaggerated in many cases as a result of an erroneous phylogenetic position for the guinea pig. The average rate of amino acid replacement in the guinea pig seems to be comparable to that in the rat and the mouse. However, the data indicate that myomorph and caviomorph genes evolve, on average, about two times faster than their human counterparts. Finally, our analysis provides evidence against the hypothesis that the gundi (an African rodent) represents the most ancient rodent lineage. PMID- 1624763 TI - Characters and the systematics of Drosophilidae. PMID- 1624764 TI - Signal, noise, and reliability in molecular phylogenetic analyses. AB - DNA sequences and other molecular data compared among organisms may contain phylogenetic signal, or they may be randomized with respect to phylogenetic history. Some method is needed to distinguish phylogenetic signal from random noise to avoid analysis of data that have been randomized with respect to the historical relationships of the taxa being compared. We analyzed 8,000 random data matrices consisting of 10-500 binary or four-state characters and 5-25 taxa to study several options for detecting signal in systematic data bases. Analysis of random data often yields a single most-parsimonious tree, especially if the number of characters examined is large and the number of taxa examined is small (both often true in molecular studies). The most-parsimonious tree inferred from random data may also be considerably shorter than the second-best alternative. The distribution of tree lengths of all tree topologies (or a random sample thereof) provides a sensitive measure of phylogenetic signal: data matrices with phylogenetic signal produce tree-length distributions that are strongly skewed to the left, whereas those composed of random noise are closer to symmetrical. In simulations of phylogeny with varying rates of mutation (up to levels that produce random variation among taxa), the skewness of tree-length distributions is closely related to the success of parsimony in finding the true phylogeny. Tables of critical values of a skewness test statistic, g1, are provided for binary and four-state characters for 10-500 characters and 5-25 taxa. These tables can be used in a rapid and efficient test for significant structure in data matrices for phylogenetic analysis. PMID- 1624765 TI - Cloning and characterization of highly polymorphic porcine microsatellites. AB - A size-fractionated (200-400 bp) porcine genomic library was screened with the dinucleotide motifs (TG)n and (TC)n. The number of TG- and TC-positive clones was 83 and four, respectively, implying that the former motif is more frequent in the porcine genome, as previously reported in other species. Twenty-six TG-clones were sequenced, and the number of repeats varied between 16 and 42 with different compositions of the repetitive sequences; 17 clones had a perfect stretch of TG repeats, four had imperfect stretches, and five had a compound structure with TG repeats followed by TC-repeats. Primers for DNA amplification using the polymerase chain reaction (PCR) were synthesized for six loci. Ten unrelated individuals (two wild boars and eight domestic pigs of the Swedish Yorkshire breed) were screened for microsatellite polymorphism. All six microsatellite loci were polymorphic with two to seven alleles and observed heterozygosities in the range of 0.42-0.84; the inheritance of the observed polymorphism was confirmed by family studies. The characteristics of microsatellites make them highly suitable as genetic markers, and these microsatellites were isolated as a part of a pig gene mapping project. PMID- 1624766 TI - Linkage analysis of five new genetic markers of the oriental fruit fly, Bactrocera dorsalis (Diptera: Tephritidae). AB - Five new autosomal recessive genes are described in the oriental fruit fly, Bactrocera dorsalis (Hendel). These genetic markers are associated into three linkage groups. The matte (mt) gene is linked to the previously described mandarin red (ma) gene, and the white puparium (wp) gene is linked to the white eye (we) and amethyst (am) loci. The third designated linkage group has the yellow eye (ye) marker. The we/we homozygote is epistatic to ye/ye, and each is epistatic to am/am and ma/ma. PMID- 1624767 TI - The inheritance of albinism in a freshwater snail, Physa heterostropha. AB - Complementation tests revealed that albinism in four laboratory strains of Physa (Physella) heterostropha pomilia resulted from two recessive, nonallelic genes. F2 dihybrid progeny displayed the 9:7 ratio classically associated with reciprocal recessive epistasis between unlinked loci. This offers a contrast to the situation in the better known planorbid snails and provides a valuable tool for the study of reproductive biology in these facultatively self-fertilizing hermaphrodites. PMID- 1624768 TI - Biochemical plasticity in the Arizona tiger salamander (Ambystoma tigrinum nebulosum). AB - The Arizona tiger salamander, Ambystoma tigrinum nebulosum, is a developmentally polymorphic species. Some individuals become sexually mature while retaining some larval traits (paedomorphs), while other individuals mature as metamorphosed salamanders. In this study, relative enzyme activities of the products of two duplicate loci in each of three enzyme systems (aconitase, malate dehydrogenase, and isocitrate dehydrogenase) were measured in paedomorphs and in paedomorphs forced to metamorphose by treatment with thyroxine. We found that thyroxine and laboratory conditions affect enzyme activities of four of the six enzymes examined and that activities of products of duplicate loci are altered to different degrees. PMID- 1624769 TI - Further evidence for latitudinal inversion clines in natural populations of Drosophila melanogaster from India. AB - Chromosomal analysis of eight Indian natural populations (six from north India and two from south India) of Drosophila melanogaster revealed the presence of 13 paracentric inversions, including one in the X chromosome. All four types of inversions--common cosmopolitan (4), rare cosmopolitan (3), recurrent endemic (2), and unique endemic (4)--were detected. The frequency of commonly occurring inversions and the level of inversion heterozygosity were found to be higher in the two southern populations. The south Indian populations are genetically more differentiated than those from the north. Also, latitudinal clines in the frequencies of the four common cosmopolitan inversions were detected. These results provide further evidence for the existence of inversion clines in Indian populations of D. melanogaster. PMID- 1624770 TI - Identifying the ptilopody (feathered shank) loci of the chicken. AB - A series of crosses was made involving lightly-, and heavily-, and non-feather shanked chickens in an attempt to clear up the confusion in the literature concerning the inheritance of feathered shanks in chickens. The Langshan and Brahma breeds were both shown to possess the same single shank-feathering locus, but because of their differences in phenotype and penetrance in the genetic crosses it was suggested that they possessed different alleles at this locus. This locus was designated as Pti-1, with Pti-1L being the Langshan allele and Pti 1B the Brahma allele. The Brahma allele was shown to be dominant over the Langshan allele. Both the Sultan and Cochin breeds were shown to possess two shank-feathering loci, and the data suggested that one of the loci in the Sultan contained the Pti-1L allele. It is hypothesized that the comparable allele in the Cochin breed was Pti-1B. It is proposed that the second locus in both of these breeds is similar, and the symbol Pti-2 is suggested. PMID- 1624771 TI - The hypotrophic axonopathy mutant in Japanese quail. AB - A new behavioral mutant showing either head or body quivering, or both, was found in Japanese quail. This trait was characterized by neurofilament deficiency in the axons of the cervical spinal cord and the optic and sciatic nerves and was named "hypotrophic axonopathy." This character was shown to be controlled by an autosomal recessive gene, for which the gene symbol hax was proposed. PMID- 1624772 TI - Mandible shape analysis in a testicular feminization (Tfm) strain of mice. AB - The role of androgens on the sexual dimorphism of mandible shape was investigated in mice carrying the X-linked gene for testicular feminization (Tfm), which is known to determine a profound insensitivity to testosterone and is associated with a severe reduction in androgen receptor levels in Tfm/Y males. Mandible shape analysis in an inbred strain of mice segregating for the Ta (tabby) and Tfm mutations showed that the sexual dimorphism observed between +Ta/+Ta females and +Ta/Y males almost disappeared between Tfm+/+Ta females and Tfm+/Y males. In addition, a canonical discriminant analysis showed that these two closely related classes, Tfm+/+Ta and Tfm+/Y, are readily differentiated from both the +Ta/+Ta and +Ta/Y classes. These results suggest that androgens are involved in the mandible shape sexual dimorphism and play a role in mandibular development in both males and females. PMID- 1624773 TI - On the displacement of single-locus polymorphisms. AB - And where, along the evolutionary track, some mutant gene did arise which was advantageous in its heterozygous degree of expression but deleterious homozygously, that gene, though temporarily multiplied as a make-shift arrangement, would usually have become replaced, after a while, by mutant genes of less deviant expression, occupying the same or other loci, which gave an equivalent advantage when they were present homozygously. For such genes would make possible a more uniform, and therefore (when all individuals were averaged) a closer approach to the adaptational optimum. PMID- 1624774 TI - A computer program for testing pairwise linkage disequilibria in subdivided populations. PMID- 1624776 TI - Health issues of international travelers. PMID- 1624775 TI - CODONS: a microcomputer program for codon usage analysis. PMID- 1624777 TI - General advice for the international traveler. AB - Medical concerns of the traveling patient may be organized into pre-travel medical advice and preparation, maintenance of health and behavioral modification during travel, and post-travel diagnosis and treatment for travelers returning with illness or a significant change in their general health. Pre-travel medical advice and preparation may be done in large part by well-informed primary-care providers, although patients with special health conditions or unusually complicated or high-risk itineraries may be best referred to a travel medicine specialist. Although diagnosis and treatment of exotic and tropical diseases usually falls within the area of expertise of the infectious diseases specialist, primary physicians should be familiar with the geographic distribution and presentation of the more common of these diseases, so that appropriate referrals will be made. PMID- 1624778 TI - Immunizations. AB - The protection of travelers against vaccine-preventable disease is an important part of pre-travel preparation. This review discusses immunizations that should be given as part of routine health maintenance, regardless of whether the individual is traveling. It also covers immunizations that may be required by a country as a condition for entry and those that are recommended because of a risk of acquiring a particular vaccine-preventable illness during travel. Prior to the administration of any of these vaccines, a careful health and immunization history and detailed travel itinerary should be obtained. PMID- 1624779 TI - Prevention of malaria. AB - Malaria is one of the most prevalent infectious diseases worldwide; it is transmitted in over 100 countries, and it is a major cause of serious morbidity and mortality in travelers. Clinicians should inform travelers of their risk, teach them the principles of personal protection, and offer individualized chemoprophylaxis regimens. The increasing prevalence of multiple drug-resistant Plasmodium falciparum in many parts of the world makes nonpharmacologic methods of malaria prevention important. PMID- 1624781 TI - The traveler's medical kit. AB - This article presents a comprehensive list of drugs and other medical supplies that may be of use to travelers for treating common infections and noninfectious travel-related illness. Recommendations are offered for using the medications to treat specific common medical problems while traveling. Sample medical kits, the contents of which vary depending on itinerary and length of stay, are presented. PMID- 1624780 TI - Prevention of traveler's diarrhea. AB - Preventing traveler's diarrhea is usually a matter of common sense, good luck, and the host's ability to defend against enteric pathogens, particularly enterotoxigenic Escherichia coli. Untreated tap water, ice cubes, unpasteurized milk products, salads, food from street vendors, and dining in unhygienic appearing restaurants should be avoided. Well-cooked food that is served hot and carbonated, commercially bottled beverages are usually safe. Food and water precautions, however, are no guarantee of success in preventing traveler's diarrhea. Bismuth subsalicylate used prophylactically is somewhat inconvenient and is only moderately effective. Although antibiotic prophylaxis is very effective for traveler's diarrhea, particularly the quinolones, it should be reserved for high-risk travelers. PMID- 1624782 TI - Medical considerations for the pregnant traveler. AB - The care of pregnant travelers requires clinical information and skills that are derived from many disciplines. Issues to be considered include the safety of both mother and fetus during commercial air travel, vigorous exercise, scuba diving, and even high-altitude trekking. Immunizations require a balanced approach to the risk of disease versus the risks of vaccine complications. Safe or treated water sources are of paramount importance to prevent unnecessary exposure to antimicrobial and antiparasitic agents during pregnancy. Malaria prophylaxis is made even more difficult by an increasingly widespread resistance of Plasmodium species to chloroquine. PMID- 1624783 TI - Medical considerations for international travel with infants and older children. AB - This article reviews preparatory guidelines for international travel with infants and children. Pre-travel immunizations, malaria chemoprophylaxis, and chemotherapy of traveler's diarrhea are reviewed. Dosages and schedules for special vaccines to consider for children are described. Practical advice for air travel and a prolonged overseas stay is offered to ensure safe and healthy international travel with infants and children. PMID- 1624784 TI - Self-help for the traveler who becomes ill. AB - While infections commonly occur in travelers, most can be prevented by avoiding fresh fruit (unless it is peeled), fresh vegetables, unpasteurized milk and cheeses, nonbottled water and ice; by taking antimalarial drugs; by using insect repellents in areas where indicated; and by using common sense. Remember also that travel does not prevent you from getting many of the illnesses you might get at home. It is essential to take any regular medications along with you. I recommend that you take such medications in your carry-on baggage, for airlines have a propensity for losing baggage that contains critical items. If you do become ill, you can take care of most illnesses yourself if you have planned ahead. PMID- 1624785 TI - Evaluation of diarrhea in the returning traveler. AB - Diarrhea in the returned traveler raises the possibility of a wide range of infectious, post-infectious, and idiopathic (e.g., inflammatory bowel disease) disorders that require a thoughtful evaluation. Specific clues in the history and clinical presentation are helpful in distinguishing inflammatory from noninflammatory processes and in suggesting persistent parasitic or other syndromes. The authors describe a practical approach to the diagnosis and management of diarrhea in the returned traveler. PMID- 1624786 TI - The returning traveler with fever. AB - The febrile returning traveler tests a clinician's knowledge of tropical medicine as well as skills in differential diagnosis. A thorough history with special emphasis placed on the patient's travel itinerary and knowledge of the geographic location and incubation times of certain tropical diseases will narrow the diagnostic possibilities. This will allow the clinician to focus the diagnostic work-up and make wise choices of laboratory tests and procedures. PMID- 1624787 TI - Evaluation of skin problems. AB - Travelers frequently return to North America with noninfectious skin problems. However, the physician who evaluates a returning traveler or immigrant with cutaneous abnormalities must also consider the possibility of infection. Attention should be paid to the nature of the skin lesions, the presence or absence of systemic manifestations, and the details of the travel history, e.g., geographic sites visited, duration of travel, activities, and prophylactic medications. This article highlights the conditions most likely to be encountered among typical immunocompetent North American travelers. PMID- 1624788 TI - Evaluation of respiratory problems. AB - Respiratory problems are common in international travelers. Most are self-limited and do not result in significant morbidity. Those that are severe enough to result in fever and an abnormal chest roentgenogram may pose diagnostic difficulties. The familiar bacterial respiratory pathogens found worldwide are the most common causes of this syndrome, but less familiar entities also need to be considered. A careful evaluation, including a thorough travel history, should yield the diagnosis. PMID- 1624789 TI - Eosinophilia in the returning traveler. AB - Eosinophilia in a traveler returning from the developing world should first and foremost suggest the possible presence of a helminth parasite. Protozoal parasites are much less commonly associated with eosinophilia. Other entities to be considered include allergies, drug reactions, and numerous other miscellaneous causes. PMID- 1624790 TI - Different regulation of class I gene expression in the adult mouse and during development. AB - The expression of the class I genes encoding for histocompatibility Ag is complex both in adult and during development. Although ubiquitously expressed in the adult, the mRNA level of class I genes is variable from one organ to another. During development, H-2K mRNA expression has two phases: the first from blastocyst to day 11, where H-2K mRNA level is extremely low, and the second, beginning after day 11, when H-2K mRNA expression increases first dramatically (10x) and then progressively to birth. To localize the sequences responsible for the regulation of H-2K gene expression in the adult and during development, we have constructed a series of transgenic strains carrying 1) a 9-kb native H-2K gene, H-2K LF, corresponding to the entire H-2Kb gene with 2 kb of upstream sequences and 3 kb of downstream sequences, and 2) two hybrid constructs linking the same 5'-flanking region of H-2Kb gene to two reporter genes, the human growth hormone and the human c-myc proto-oncogene. Expression of the transgenes was compared with that of the endogeneous H-2K gene in adult organs and during development of the different transgenic strains. In the adult, the three constructs behave almost like the endogeneous H-2K gene, but the H-2K LF construct is the only one whose expression is independent of the integration site and related to the copy number. During development, both fusion genes are barely expressed in the embryo as well as in the extra-embryonic tissues, whereas the H 2K LF transgene expression parallels that of the endogeneous class I gene. Therefore, our results show that H-2K developmental regulatory sequences are not included in the region that controls H-2K mRNA expression in the adult, indicating that H-2K class I gene expression in adult organs and in development is regulated by different mechanisms. PMID- 1624791 TI - Functional expression of human CD8 in fully reconstituted mice after retroviral mediated gene transfer of hemopoietic stem cells. AB - Retroviral-mediated gene transfer has been used in an attempt to efficiently and stably express functional cell-surface molecules in lymphoid and myeloid cells. The human CD8 molecule is a T cell-specific surface receptor that is intimately involved in class I MHC-restricted Ag recognition and subsequent T cell activation. After infection with a recombinant, replication-defective retrovirus containing the human CD8 alpha cDNA, bone marrow cells were transplanted into lethally irradiated recipients. The majority of lymphoid and myeloid cells of reconstituted animals expressed high levels of human CD8 for at least 8 months after transplantation. Transfer of bone marrow and spleen cells from these recipients 100 days after transplantation into secondary recipients also resulted in long term expression of CD8 in lymphoid and myeloid cells. CD8 expressed in splenic T cells associated with the lymphoid-specific tyrosine protein kinase p56lck, participated in T cell activation and conferred an increased xenogeneic response to human MHC class I Ag. Thus, retroviral-mediated gene transfer allows the long term, functional expression of cell-surface molecules in normal murine lymphoid and myeloid cells. PMID- 1624792 TI - Lectin specificity and binding characteristics of human C-reactive protein. AB - C-reactive protein (CRP) is thought to play an important role in immunomodulation. The exact biologic function of this pentraxin protein is, however, still unclear. Here we report experiments designed to further characterize the binding properties of CRP. Using purified human CRP it could be shown that CRP immobilized onto polystyrene surfaces or onto latex beads binds distinct plasma glycoproteins including IgG, asialofetuin, asialo-beta 2 glycoprotein I and, likewise, synthetic glycoproteins as a lectin, exhibiting binding specificity for terminal galactosyl residues of the glycoprotein glycans. Binding of CRP to IgA, IgM, IgG, asialofetuin, asialo-beta 2-glycoprotein I and to synthetic glycoproteins requires immobilization onto surfaces of both CRP and the ligand. Fibronectin and fibrinogen are bound by surface-immobilized CRP also in soluble phase. Comparing various mono-, di-, and trisaccharides as competitive inhibitors of the lectin binding activity of CRP, only beta-D-Gal-(1-3)-D-GalNAc, beta-D-Gal-(1-4)-D-GalNAc, and beta-D-Gal-(1-4)-beta-D-Gal-(1-4)-D-GlcNAc had significant inhibitory power at a concentration of 8 mmol/liter. Binding activity of CRP was pH-dependent with an optimum at pH 5 to 6 and was reduced by 90% when pH was shifted from 6 to the physiologic pH value of 7.4. CRP exhibited lectin like properties with binding specificity for galactosyl residues also when bound to K-562 erythroleukemia cells. It is therefore suggested that CRP immobilized onto surfaces exhibits lectin activity toward galactosyl groups preferentially in a mildly acidic environment as present at sites of inflammation. PMID- 1624793 TI - Cloning and expression of recombinant Aspergillus fumigatus allergen I/a (rAsp f I/a) with IgE binding and type I skin test activity. AB - Aspergillus fumigatus secretes an 18-kDa nonglycosylated IgE-binding protein. This protein was previously shown to be a ribotoxin, like alpha-sarcin and mitogillin. A 686-bp long A. fumigatus cDNA encoding an 18-kDa ribotoxin was cloned and expressed in Escherichia coli as a fusion protein with six adjacent histidines (rAsp f I/a). rAsp f I/a was purified to homogeneity by Ni(2+)-chelate affinity chromatography and refolded. The recombinant protein was enzymatically active resulting in the cleavage of 28S rRNA within a universally conserved region. rAsp f I/a was cytotoxic for EBV immortalized or PHA stimulated human PBMC. Furthermore, rAsp f I/a was recognized by murine mAb made against an 18-kDa ribotoxin. IgE of individuals allergic to A. fumigatus bound to rAsp f I/a as shown by ELISA, dot blots, and Western blots. rAsp f I/a elicited positive immediate type I skin reactions in individuals allergic to A. fumigatus but not in healthy control individuals. The results show that rAsp f I/a has similar functional characteristics when compared to the native 18-kDa ribotoxin. rAsp f I/a expressed in E. coli can therefore be used as a standardized Ag/allergen for serologic and clinical diagnosis of A. fumigatus-associated diseases. PMID- 1624794 TI - Mhc-DQB repertoire variation in hominoid and Old World primate species. AB - Comparison of 87 distinct Mhc-DQB sequences, obtained from 13 primate species, demonstrates that five out of eight trans-species Mhc-DQB allele lineages are at least 30 million years old and predate divergence of hominoid and Old World primate species. One lineage may be much older because its members are not only traced back in higher primates, but also are present in a New World primate species. Comparing Mhc-DQB repertoire variation in distinct species, allows one to pinpoint when certain polymorphisms were lost or gained in primate evolution. Heterogeneity observed among members of trans-species Mhc-DQB allele lineages can be explained in major part by point mutations, whereas intraexonic crossing-over is a potent mechanism in generating new allele lineages. The stability of Mhc-DQB polymorphisms is influenced by selective forces because distinct allele lineages appear to have accumulated nucleotide substitutions and amino acid replacements at different rates. PMID- 1624795 TI - Rat secretory component binds poorly to rodent IgM. AB - Our previous studies and those of others indicated that human secretory component (SC), the five domain extracellular portion of the poly Ig receptor, binds avidly to both pIgA and IgM. In this study we report that in rodents, SC binds primarily to pIgA. Rat secretory component was isolated from bile and radiolabeled to known specific activity with 125I. Radiolabeled rat SC was incubated with rat and mouse monoclonal proteins for 1 h at room temperature and overnight at 4 degrees D. Binding of 125I-rat SC to Ig was determined in two ways: 1) immunoprecipitation of putative 125I-rat SC-Ig complexes with anti-L chain antibodies; 2) HPLC gel filtration on an analytical TSK 4000 column that separated free 125I-rat SC from 125I-rat SC bound to Ig. Both methods of analysis yielded similar results. Rat and mouse polymeric (p) IgA bound rat SC with high avidity, although the binding activity of the IgM from either species was virtually nil. The number of SC binding sites on rat polymeric Ig was determined by immunoprecipitation of mixtures of rat pIg with saturating concentrations of 125I-rat SC and yielded values of 1.0 and 0.05 for rat pIgA and IgM, respectively. The significance of these findings with respect to the biologic function of the pIg R in rodents and the nature of the pIg R-binding site on pIg is discussed. PMID- 1624796 TI - Sequence analysis of members of the human Ig VH4 gene family derived from a single VH locus. Identification of novel germ-line members. AB - We have generated a mouse x human heterohybridoma that contains a single copy of chromosome 14 and, thus, a haploid set of Ig VH genes. This cell line was used to investigate the germ-line content and nucleotide sequences of members of the VH4 gene family in a polymerase chain reaction-based approach. The analysis of 58 full-length sequences revealed the presence of 12 different germ-line VH4 genes, each of which is potentially functional. These germ-line VH4 genes were compared with the nucleotide sequences of published VH4 genes. Three VH4 genes were 100% identical to previously published sequences and belong to a group of VH4 genes that are strongly conserved and highly prevalent in the human population. Three VH4 genes in our collection displayed greater than 99.3% sequence identity with reported germ-line VH4 sequences and likely represent allelic counterparts of these genes. Six genes displayed less than 97.2% sequence identity with published VH4 genes and were identified as novel members of the human VH4 gene family or more distantly related alleles of known VH4 genes. Collectively, these data suggest that, overall, the human VH4 gene family may be more diverse than hitherto assumed, whereas a number of individual members are nonpolymorphic and extremely well conserved. PMID- 1624797 TI - The pattern of joining (JH) gene usage in the human IgH chain is established predominantly at the B precursor cell stage. AB - Preferential utilization of JH and D genes has been demonstrated in the rearranged IgH chain in human peripheral B cells. We report here that the same hierarchy of JH gene usage is observed in leukemic cells arrested in the B precursor stage of differentiation. Specifically, JH4 and JH6 accounted for 42.9% and 35.7%, respectively, of the JH gene usage in the leukemias compared with an expected frequency of 16.7% assuming unbiased gene usage. Within the D gene families, the DN1 gene appears to be overutilized in both populations, representing about 15% of the total gene usage compared with an expected frequency of 3.2%. Because 21 of the 36 leukemias contained only nonproductive IgH rearrangements, the preferential gene usage could not have arisen from pre-B cells that have undergone clonal selection after a productive rearrangement but before surface Ig expression. Nonproductive rearrangements exhibited the biased gene usage seen for productive rearrangements. These findings suggest that a recombination bias favoring certain segments may be the actual mechanism responsible for the apparent preferential utilization of JH and D genes. PMID- 1624798 TI - Transforming growth factor-beta 1 inhibits murine immediate and delayed type hypersensitivity. AB - Transforming growth factor beta 1 (TGF-beta 1) is a member of a gene superfamily that regulates growth, differentiation, and function of cells including several in vitro immune functions. Our study examined the systemic effect of TGF-beta 1 on murine delayed-type hypersensitivity (DTH), a model of T cell-mediated immunity that may depend on mast cells. Mice were immunized by i.v. injection of SRBC or by topical application of picryl chloride, and the responses were elicited by cutaneous challenge with the appropriate Ag. Systemic administration of TGF-beta 1 at the time of Ag challenge significantly reduced both the early and late phases of DTH. The effect of TGF-beta 1 on the release of serotonin from mouse peritoneal mast cells was examined. Results indicated that in vivo treatment with TGF-beta 1 24 h before mast cell harvest inhibited the in vitro release of serotonin in response to challenge with compound 48/80, or anti-IgE antibody. In contrast, treatment with TGF-beta 1 24 h before Ag challenge did not inhibit DTH indicating that mast cells may not be the direct target for TGF-beta 1 in the DTH models. In vivo treatment with TGF-beta 1 inhibited the IgE mediated, mast cell-dependent, immediate hypersensitivity skin swelling response when injected at the time of, or 24 h before challenge. This suggests an effect on mast cells and a regulatory role for TGF-beta 1 in IgE-mediated responses. PMID- 1624799 TI - IFN-gamma and IL-2 cooperatively activate NF kappa B in murine peritoneal macrophages. AB - The combination of IFN-gamma and IL-2 has been demonstrated to induce or promote transcription from selected inflammatory cytokine genes in both monocytes and macrophages. In the present report, we have evaluated the ability of these agents to activate nuclear proteins, in murine peritoneal macrophages, that are capable of specific binding to the kappa B nucleotide consensus sequence (e.g., nuclear factor binding the kappa B consensus sequence (NF kappa B)), which is present in the region 5' of the transcription start site of many cytokine genes. Both IFN gamma and IL-2 treatments alone caused some activation of NF kappa B, as evidenced by the appearance of a characteristic DNA-protein complex in electrophoretic mobility shift assays; in combination, the two agents cooperated to increase binding activity markedly, to a level equivalent to that seen in macrophages stimulated with LPS, another potent stimulus of macrophage cytokine gene expression. The binding activity was directed toward the kappa B sequence, based upon competition studies with several different oligonucleotide probes containing the kappa B motif in different contexts. The complex formed in cells stimulated with either IFN-gamma/IL-2 or LPS contained two proteins, of approximately 50 kDa and 65 kDa, based upon UV cross-linking experiments with a bromodeoxyuridine-substituted oligonucleotide probe. Although the effects of LPS and IFN-gamma/IL-2 on NF kappa B activity were both transient, response to LPS was detected earlier and declined more rapidly than that seen with IFN-gamma/IL-2 treatment. The cooperative activation of NF kappa B was dose dependent for both IFN-gamma and IL-2. The activation of NF kappa B by IFN-gamma/IL-2 did not depend upon protein synthesis. These results suggest that the induction of cytokine gene expression in macrophages by the combination of IFN-gamma and IL-2 may involve the activation of NF kappa B. PMID- 1624800 TI - Insulin-like growth factor-I inhibits apoptosis in IL-3-dependent hemopoietic cells. AB - The death of hemopoietic cells on withdrawal of CSF occurs by a mechanism known as apoptosis characterized by the early degradation of chromatin into oligonucleosome-length fragments. Insulin-like growth factor I plays a pivotal role in the regulation of somatic cell growth as a mediator of growth hormone action. Animals with low levels of circulating IGF-I are more vulnerable to infections and have diminished immune responses. To analyze the possibility of a regulatory role of IGF-I on hemopoiesis and determine its mechanism of action, we have studied the effect of this growth factor on the survival and proliferation of two IL-3-dependent hemopoietic cell lines and in IL-3-responsive primary cultures of bone marrow-derived mast cells. In IL-3-depleted cultures, IGF-I prevented DNA fragmentation and apoptotic cell death. Insulin at high concentration had a weak protective action and IGF-II was inactive in suppressing apoptosis in these IL-3-dependent hemopoietic cells. Cell proliferation was also stimulated by IGF-I in the absence of other hemopoietic growth factors although it was a weak mitogen when compared with IL-3. These results indicate that circulating or locally produced IGF-I may promote survival of both the steady state hemopoietic precursor population and cytokine-producing cells and could therefore regulate hemopoiesis acting in a concerted manner with other CSF. PMID- 1624801 TI - Cytokine production induced by Mycobacterium tuberculosis lipoarabinomannan. Relationship to chemical structure. AB - Lipoarabinomannan (LAM), a major cell wall component of Mycobacterium tuberculosis, exhibits a wide spectrum of immunoregulatory effects. To identify cytokines produced by human PBMC in response to LAM, we used PCR amplification to detect cytokine mRNA. LAM-induced transcription of mRNA for cytokines characteristically produced by macrophages, including TNF, granulocyte-macrophage CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8, and IL-10. In contrast, LAM did not induce transcription of mRNA for cytokines produced predominantly by lymphocytes, such as lymphotoxin, IFN-gamma, IL-2, IL-3, or IL-4. Measurement of concentrations of TNF, granulocyte-macrophage-CSF, IL-6, IL-10, IFN-gamma, IL-2, and IL-4 in cell culture supernatants indicated that cytokine release correlated with mRNA patterns. Lipomannan (LM) and phosphatidylinositol mannosides (PIM) are simpler versions of LAM. LM lacks arabinan, whereas PIM lacks both arabinan and most mannan residues. LAM, LM, and PIM induced transcription of cytokine mRNA, elicited cytokine production, and suppressed Ag-induced T cell proliferation, indicating that most of the biologic activity of LAM was associated with the phosphatidylinositol end of the molecule. In support of this conclusion, deacylation of LAM abrogated its capacity to induce cytokine production and suppress Ag-induced proliferation. The production of macrophage-derived cytokines induced by LAM may mediate clinical manifestations of tuberculosis such as fever, weight loss, and tissue necrosis, as well as immunoregulatory effects such as inhibition of Ag-induced proliferation and hyperglobulinemia. PMID- 1624802 TI - A carboxyl-terminal fragment of Plasmodium falciparum gp195 expressed by a recombinant baculovirus induces antibodies that completely inhibit parasite growth. AB - The major merozoite surface Ag (gp195) of Plasmodium falciparum has been shown to protect monkeys against parasite infection, and gp195-based synthetic peptides and recombinant polypeptides have been evaluated as potential malaria vaccines. A major problem in developing a gp195-based recombinant vaccine has been the difficulty in obtaining a recombinant polypeptide that is immunologically equivalent to the native protein. In this study, the carboxyl-terminal processing fragment (p42) of gp195 was produced in yeast and in a baculovirus recombinant system. Immunologic analyses indicated that the secreted baculovirus p42 (BVp42) expressed native, disulfide-dependent conformational epitopes, whereas these epitopes were poorly represented in the intracellular yeast p42. BVp42, but not yeast p42, was also recognized by the majority of gp195-specific antibodies of animals immunized with purified native gp195, indicating that the anti-gp195 response of these animals was focused on conformational determinants of the p42 processing fragment. Sera against native gp195 of congenic mice of diverse H-2 haplotypes recognized the BVp42 polypeptide, demonstrating that a genetically heterogeneous population is capable of responding to p42 epitopes. BVp42 was highly immunogenic and induced high titers of antibodies that were cross-reactive with purified native gp195 in an ELISA and also reacted with schizonts and merozoites by immunofluorescence. Anti-BVp42 antibodies completely inhibited the in vitro growth of the malaria parasite, whereas anti-yeast p42 antibodies had no effect. These results indicate that native, conformational epitopes of p42 are critical for the induction of gp195-specific, parasite growth-inhibitory antibodies and that the BVp42 polypeptide efficiently induces antibodies specific for these native determinants. PMID- 1624803 TI - Constitutive IL-2 mRNA expression in lymphocytes, infected with the intracellular parasite Theileria parva. AB - Theileria parva-infected lymphoblastoid cell lines of T or B cell origin were examined for IL-2 mRNA expression. T. parva-infected T cell lines could be of the CD4-CD8-, CD4+CD8-, CD4-CD8+, or CD4+CD8+ phenotype and express alpha beta or gamma delta TCR. By Northern blot analysis and amplification by the polymerase chain reaction, IL-2 mRNA could be detected in all T. parva-infected cell lines tested. IL-2 mRNA expression was also shown to be dependent on the continuous presence of the parasite in the host cell cytoplasm, because elimination of the parasite by treatment of T. parva-infected cell cultures with the theilericidal drug BW720c resulted in the disappearance of detectable IL-2 mRNA. The effect of anti-IL-2 antibodies on the proliferation of T. parva-infected cells was also tested. Inhibition experiments suggest that although IL-2 mRNA can be detected in all cell lines tested, not all T. parva-infected cell lines are dependent on IL-2 for their proliferation. Our data provide the first example for the constitutive expression of IL-2 mRNA in T and B cells caused by infection with an intracellular parasite. PMID- 1624804 TI - Digestion of Histoplasma capsulatum yeasts by human macrophages. AB - The strategies used by Histoplasma capsulatum yeasts to survive and multiply within human macrophages (M phi) are unknown. To better understand these strategies we studied the intracellular fate of viable vs heat-killed (HK) yeasts in human monocyte-derived M phi. Initial studies demonstrated that phagolysosome fusion was present in M phi ingesting either viable or HK yeasts. Viable yeasts multiplied within M phi phagolysosomes, whereas M phi completely digested intracellular FITC-labeled HK yeasts within 24 h after ingestion. This observation was confirmed by electron microscopy. M phi that had ingested colloidal gold-labeled HK yeasts contained gold particles but no visible yeasts at 24 h. Digestion of HK yeasts was evident as early as 4 h after phagocytosis, and was complete by 24 h. M phi digestion of HK yeasts was blocked completely when M phi were cultured for 24 h in the presence of chloroquine. In M phi simultaneously ingesting both viable and HK yeasts, viable yeasts multiplied, but HK yeasts were digested within the same cell. M phi that had ingested viable yeasts digested them completely when M phi were cultured for 24 h in the presence of cycloheximide or amphotericin B. Coculture of infected M phi with nystatin or ketoconazole resulted in inhibition of growth, but the yeasts were not digested. These data indicate that: 1), HK Hc yeasts are easily digested by preformed M phi lysosomal hydrolases; 2), viable Hc yeasts survive and multiply within M phi phagolysosomes, but the yeasts do not secrete a factor(s) that affects the ability of other phagolysosomes within the same M phi to digest killed yeasts; and 3), inhibition of yeast protein synthesis or cell wall biosynthesis is sufficient to render viable yeasts susceptible to digestion by human M phi. PMID- 1624805 TI - Calcium rather than protein kinase C is the major factor to activate phospholipase D in FMLP-stimulated rabbit peritoneal neutrophils. Possible involvement of calmodulin/myosin L chain kinase pathway. AB - In the present study, we first investigated which of the factors, protein kinase C (PKC) or Ca2+, plays an important role in activation of phospholipase D (PLD) of rabbit peritoneal neutrophils stimulated by the chemoattractant FMLP. PLD activity was assessed by measuring [3H]phosphatidylethanol ([3H]PEt), the unambiguous marker of PLD, generated by [3H]lyso platelet-activating factor prelabeled neutrophils in the presence of ethanol. PKC inhibitors, staurosporine and 1-(5-isoquinolinesulfonyl-2-methylpiperazine dihydrochloride, augmented the plateau level of [3H]PEt produced in FMLP-stimulated cells, although they had no effect on the initial rate of the formation. Furthermore, it was found that the FMLP-stimulated [3H]PEt formation was inhibited by pretreatment of cells with PMA, a PKC activator, and exposure of cells to staurosporine before PMA pretreatment moderately blocked the PMA inhibition. Ca2+ ionophore ionomycin, as well as FMLP, stimulated [3H]PEt formation, accompanied by a decrease in [3H]phosphatidylcholine, in a time- and concentration-dependent manner. Both FMLP and ionomycin absolutely required extracellular Ca2+ to increase [3H]PEt formation. These results imply that elevated intercellular Ca2+ by FMLP stimulation is the major factor for PLD activation and that PKC rather negatively regulates the enzyme activity. Interestingly, a calmodulin inhibitor, N-(6 aminohexyl)-5-chloro-1- naphthalenesulfonamide, and a myosin L chain kinase inhibitor, 1-(5-iodonaphthalene-1-sulfonyl)-1H-h exahydro-1,4-diazepine hydrochloride, both inhibited the ionomycin- and FMLP-stimulated [3H]PEt formation in a concentration-dependent manner. Results obtained in this study suggest that, in FMLP-stimulated rabbit peritoneal neutrophils, increased intracellular Ca2+ activates PLD through calmodulin/myosin L chain kinase pathway and, thereafter, the enzyme activation is turned off by simultaneously activated PKC. PMID- 1624806 TI - Release of granule proteins from eosinophils cultured with IL-5. AB - Eosinophils isolated from normal individuals were cultured in the presence of human rIL-5 (hrIL-5) for up to 14 days, and the effects of this exposure were determined. First, the hrIL-5-cultured eosinophils were activated and degranulated more readily than freshly isolated eosinophils. For example, eosinophils cultured for 7 days with hrIL-5 released 30 and 10% of granule eosinophil-derived neurotoxin (EDN) when exposed to Sepharose 4B beads coupled to secretory IgA and IgG, respectively, whereas freshly isolated eosinophils released only 19 and 4%, respectively, of their EDN in response to the same stimuli. Degranulation of hrIL-5-cultured eosinophils was not augmented by further exposure to hrIL-5, whereas degranulation of freshly isolated cells to secretory IgA and IgG beads was increased by exposure to hrIL-5. Second, eosinophils cultured with hrIL-5 had prolonged viability in vitro. For example, after four days of culture with 50 U/ml of hrIL-5, 86% of eosinophils were viable compared to 12% in medium alone. Third, hrIL-5-cultured eosinophils became hypodense, and electron microscopy showed that they contained granules with core and matrix lucency and with evidence of granule fusion. Fourth, hrIL-5-cultured eosinophils spontaneously lost 30 to 60% of their EDN, eosinophil cationic protein, and eosinophil peroxidase and about 50% of their eosinophil granule major basic protein content compared to freshly isolated eosinophils, and all four of the granule proteins were released into the culture medium. Fifth, detailed studies of eosinophils cultured in hrIL-5 showed that 89 +/- 10% of the starting quantity of EDN could be recovered at 7 days. Whereas 99 +/- 1% of the EDN at day 0 was cell associated, by 7 days 60 +/- 9% was in the cell supernatants. Thus, hrIL-5 activates eosinophils, increases their viability, decreases their density, and their content of granule proteins and causes release of the granule proteins into culture fluids. The striking loss of granule proteins during culture with hrIL-5 may be an important mechanism for deposition of these cationic toxins in various diseases where IL-5 plays a role. PMID- 1624807 TI - Eosinophil granule cationic proteins regulate complement. I. Activity on the alternative pathway. AB - Eosinophil granules contain several cationic proteins that mediate tissue damage in allergic disease. The present study examined the capacity and mechanisms by which these cationic proteins regulate activity of the alternative pathway of C. Eosinophil peroxidase and eosinophil cationic protein inhibited formation of cell bound alternative pathway C3 convertase, causing 50% inhibition of lysis at about 0.19 and 0.75 microgram/10(7) cellular intermediates, respectively. Major basic protein inhibited alternative pathway C3 activity by only 19% at 1.5 micrograms/10(7) cellular intermediates. Eosinophil-derived neurotoxin had no activity on the alternative pathway. The eosinophil granule proteins were examined for the mechanism by which they inhibited alternative pathway activity. Eosinophil peroxidase and major basic protein inhibited fluid phase factor B consumption in a reaction mixture that also contained factors D and C3b, eosinophil-derived neurotoxin had no activity on factor B consumption, and eosinophil cationic protein consumed factor B in the absence of C3b and factor D. Both eosinophil cationic protein and eosinophil peroxidase enhanced the decay of preformed alternative pathway convertase. Lysis of EAC4b,3b cellular intermediates formed to contain a low surface amount of C3b was more inhibited than was lysis of cells formed with a standard amount of C3b on the surface. This suggests that these eosinophil proteins acted predominantly on C3b to regulate alternative pathway activity. We also found that none of the eosinophil granule cationic proteins had any effect on later events after the formation of the C3 convertase. We conclude that although eosinophil-derived neurotoxin (isoelectric pH value (pI) = 8.9) does not regulate alternative pathway activity, the more highly charged eosinophil granule cationic proteins--major basic protein (pI = 10.9), eosinophil cationic protein (pI = 10.8), and eosinophil peroxidase (pI = 10.8)--do share the capacity to regulate C activity and may exert this activity in vivo. PMID- 1624808 TI - Evidence for the expression of non-HLA-A,-B,-C class I genes in the human fetal liver. AB - HLA class I Ag expression was investigated in the human fetal liver. By immunostaining, mAb to monomorphic class I Ag showed widespread reactivity with both epithelial and hemopoietic cells. By contrast, mAb to polymorphic determinants showed more restricted reactivity that was confined to a proportion of hemopoietic cells: the hepatic epithelium was essentially unreactive. This suggested that the developing liver might express nonclassical HLA class I. Class I Ag were examined in membrane and cytosol fractions of mid-trimester fetal liver. Because of its broad reactivity with HLA-A,-B, mAb Q1/28 was selected to identify classical class I Ag in these studies. Immunoprecipitations were carried out against radiolabeled glycoprotein extracts of fetal liver membranes. W6/32 detected a 40-kDa product characteristic of nonclassical class I proteins, as well as a 43-kDa product, in lysates immunodepleted with Q1/28. By immunoblotting, an anti-H chain antiserum (HC) identified a Q1/28- 40-kDa component and a 43-kDa Q1/28+ component in fetal liver membrane glycoproteins. The fetal liver cytosol fraction was found to contain a 42- to 43-kDa product by W6/32-chromatography. This component partitioned to the aqueous phase upon condensation in TritonX-114 detergent and by immunoblotting was reactive with monomorphic mAb HC10 but not with Q1/28. Total RNA and polymerase chain reaction amplified class I transcripts of fetal liver were probed using oligonucleotides specific for HLA-E, -F, and -G. HLA-F, was readily detected in total RNAs by Northern analysis. HLA-E, HLA-F, and HLA-G were all detected in fetal liver by polymerase chain reaction. Differential expression of these genes may occur between the first and second trimester of liver development. Overall therefore, the human fetal liver expresses multiple class I protein products and contains transcripts for non-classical class I genes; particularly HLA-F. PMID- 1624809 TI - Production of monocyte chemoattractant protein-1 by inflamed synovial tissue and cultured synoviocytes. AB - This study analyzes the expression of monocyte chemoattractant protein-1 (MCP-1) by inflamed synovial tissue and defines its regulation in cultured synoviocytes. Synoviocytes from patients with rheumatoid arthritis and osteoarthritis express the 0.7-kb MCP-1 mRNA. Stimulation of synoviocytes with IL-1, TNF-alpha, LPS, platelet-derived growth factor, and transforming growth factor-beta-1, but not with basic fibroblast growth factor causes a marked increase in MCP-1 mRNA levels. Expression of the MCP-1 gene is inducible by activators of the protein kinase A (cAMP) and C (PMA) signal transduction pathways and is differentially regulated by the steroids dexamethasone and retinoic acid. Cultured synoviocytes de novo synthesize 12-, 15-, and 15.2-kDa MCP-1 proteins, which increase after stimulation with IL-1. Synovial tissues from donors without joint disease and from patients with rheumatoid or osteoarthritis were analyzed for MCP-1 mRNA expression by in situ hybridization. In these samples MCP-1 mRNA expressing cells were predominantly found in the sublining cell layers, whereas specimens of normal synovial tissue contained only few positive cells. These results identify synoviocytes as a source of MCP-1. Its expression is controlled by peptide regulatory factors that are known to be present in arthritic joints. Detection of cells producing MCP-1 mRNA in synovial tissues from patients with arthritis shows that this gene is expressed in vivo and suggests that MCP-1 can play a role in recruiting monocytes in joint inflammation. PMID- 1624810 TI - Simian immunodeficiency virus-specific cytotoxic T lymphocytes are present in the AIDS-associated skin rash in rhesus monkeys. AB - An infiltration of CD8+ lymphocytes in the dermis and epidermis underlies the skin rash that commonly occurs as a primary manifestation of an AIDS virus infection. These cutaneous lymphocytes were characterized in simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys. Skin rash associated lymphocytes exhibited greater lysis of SIVmac-expressing target cells and a higher cloning efficiency for SIVmac-specific effector T cells than PBL. Moreover, both SIVmac envelope- and gag-specific CTL could be readily cloned from these skin rash-associated lymphocytes. In fact, the skin rash-associated CTL exhibited the same MHC restriction and epitope specificity as those CTL derived from PBL. These studies, therefore, demonstrate that the cutaneous infiltrating CD8+ lymphocytes in SIVmac-infected rhesus monkeys include SIVmac-specific CTL. Thus, whereas virus-specific CTL are likely to represent an important mechanism for controlling AIDS virus infections, they also may play a role in the pathogenesis of the skin lesions that occur after this infection. PMID- 1624811 TI - Varicella in pregnancy, the fetus, and the newborn: problems in management. AB - As many as 9000 pregnancies annually may be complicated by varicella, which creates management problems for the woman and her fetus or newborn. Estimates on risk to the fetus and to neonates vary widely, making counseling difficult. Likewise, the efficacy of passive immunization of pregnant women or their exposed newborns is not precisely known. In addition to these problems in clinical management, questions remain about the developmental immunology of varicella zoster virus infection. For example, why do infants exposed in utero to the virus get zoster at an early age and why does passive immunization of newborns appear to be less effective than immunization of older individuals? PMID- 1624812 TI - A long-term survey of morphine in cancer pain patients. AB - We surveyed 550 cancer patients who experienced pain and were treated with morphine for a total of 22,525 treatment days. Sufficient pain relief was achieved during more than 80% of this time using an average oral morphine dose of 82.4 mg--significantly lower than other studies. The use of this low dose, which was possible due to the concomitant administration of nonopioids and specific coanalgesics in most patients, resulted in a low incidence of side effects. Constipation and nausea/vomiting were the most common of these side effects. Physical dependence posed no practical problem in discontinuation of morphine treatment. Long-term opioid intake and development of tolerance did not appear to be linked; an increase in morphine dosage was most often explained by progression of the terminal disease. Addiction was a negligible problem, with only one observed case. PMID- 1624813 TI - The assessment of pain intensity in patients with cognitive failure: a preliminary report. AB - We reviewed our experience with 14 consecutive patients with cancer pain who developed severe cognitive failure that reverted either spontaneously or after specific treatment. In 3 patients who developed a nonagitated cognitive failure episode (CFE), there was no difference in the pain intensity measured by the patient before and after the episode and that measured by the nurse during the episode. In 11 patients who developed an agitated CFE, pain intensity assessed by a nurse during the CFE was significantly higher than the patient's assessment, both before and after the CFE. Patients who developed agitated CFE received a mean of 5 +/- 2 extra doses of narcotics per day, versus a mean of 2.17 +/- 1.6 doses in the average patient in our unit (P less than 0.01). Upon complete recovery, none of the 14 patients recalled having had any discomfort during the CFE. Problematic conflict between staff and family was detected in 4 of 11 cases of agitated CFE (36%), versus an expected 13 of 260 cases (5%, P less than 0.01). We conclude that (a) patients who recover from a severe CFE have no memory of pain; (b) medical and nursing staff are likely to overestimate the level of pain of patients with agitated CFE; and (c) agitated CFE in patients with cancer pain is a major source of distress for the patients' families and staff. PMID- 1624814 TI - Psychological techniques for controlling the adverse side effects of cancer chemotherapy: findings from a decade of research. AB - Cancer patients receiving chemotherapeutic treatments often experience unpleasant side effects that compromise the quality of their life and may be so severe that they lead to suboptimal drug dosages, missed treatments, or even discontinuation of treatment. In recent years it has been discovered that some of these side effects result from maladaptive learning. This article reviews over 10 years of research conducted at Vanderbilt University on the prevention and treatment of these psychological side effects. This research includes the assessment of the efficacy of a behavioral relaxation technique, the exploration of procedures that make this intervention clinically practical for widespread application, research aimed at predicting which patients will and will not benefit from the intervention, and the comparison of this intervention to alternative treatment approaches. The review of this research generates four major conclusions and points to several important areas for future inquiry. PMID- 1624815 TI - Comprehensive and multidimensional assessment and measurement of pain. AB - Current theories of pain and clinical experience support a multidimensional framework for the experience of pain that has implications for assessment and management in any setting. Six major dimensions have been identified: physiologic, sensory, affective, cognitive, behavioral, and sociocultural. Any clinical assessment process must address relevant dimensions of pain in the given setting. In acute care settings, for example, clinicians may focus on physiologic and sensory dimensions, whereas in chronic care settings, the affective, cognitive, and behavioral dimensions might assume priority. Various tools are available for multidimensional assessment of pain, spanning the dimensions of the experience from physiologic to sociocultural. The clinician in any setting must use appropriate tools that provide useful information. Guidelines helpful in a selection process include identification of relevant dimensions of pain, type of pain, patient population and setting, psychometric properties of the tool, and issues of time, clinical relevance, and feasibility. When a careful selection process occurs, the resulting data should simultaneously meet clinicians' needs for information as well as provide the foundation for initiation of multidisciplinary interventions. PMID- 1624816 TI - Postherpes simplex type 1 neuralgia simulating postherpetic neuralgia. AB - Patients with prodromal neuralgia associated with recurrent herpes simplex type 1 (HST1) infection and chronic facial pain following years of relapsing HST1 have been described. Chronic neuralgia following a single clinical HST1 infection and simulating postherpetic neuralgia has not been previously reported. Such a case is described: A 49-yr-old woman with a 2-mo history of oral-facial dyskinesia developed burning pain and hypersensitivity of the left side of the tongue, lower gum, and inner cheek, followed 1 day later by a vesicular rash in the same painful distribution. Viral cultures of the lesions identified HST1 but not herpes zoster. Cerebrospinal fluid analyses during the vesicular lesion stage and 1 mo later were normal with no viral growth. Oral and facial lesions resolved after 10 days; acyclovir was given for 3 wk. Brain and brainstem magnetic resonance imaging (MRI), electroencephalogram, and brainstem evoked potential studies were normal. Hyperesthesias, allodynia, and burning pain persisted despite nonsteroidal antiinflammatory agents, codeine and hydrocodone. Oral opioids were administered until sedation occurred, with no relief of pain. The burning pain and hyperesthesia resolved after the 16th day of amitriptyline use, 75 mg/day. A trial off amitriptyline 6 mo later resulted in recurrence of pain, and amitriptyline was restarted with good pain control. Post-HST1 neuralgia may simulate postherpetic neuralgia clinically, and painful symptoms may respond to amitriptyline. PMID- 1624817 TI - [Persistent non-inflammatory carriage of group B Streptococcus in organs of newborn mice]. AB - Group B Streptococcus (GBS) is an important pathogen in newborn infants and has shown a remarkable increase in Japan since 1970. It has been reported that the early-onset type of GBS infection may be caused by vertical transmission whereas the late-onset type may be caused by horizontal or nosocomial transmission. However we think that the late-onset type may be caused by continuous carriage of GBS after vertical transmission. Therefore, we studied the continuous carriage of GBS using mice. Mice were separated into two groups, and one was given 10(3) colony-forming units of type Ia and the other type III GBS (isolated from the affected human neonates) by intraperitoneal injection on the first day of life. Then, on the 2nd, the 5th, the 8th and the 10th day after injection, viable counts were obtained per 10 mg of liver, spleen, lung and brain tissues. Each organ was homogenized and dissolved in 1 ml physiological saline per 10 mg of tissue, and 0.1 ml of each was infused into brain-heart infusion agar and incubated for 36 hours at 37 degrees C. The type III GBS isolated from many organs on these days, but type Ia was isolated in only two among 72 mice. These results suggested the possibility that type III GBS acquired by vertical transmission at birth may be carried over in a non-inflammatory state for a long time, and that the symptoms will become manifest only when the host-parasite relationship is disturbed later. PMID- 1624818 TI - [Studies on Clostridium absonum isolates from clinical specimens]. AB - Two strains of Clostridium absonum isolated from clinical specimens and a type strain were tested for heat resistance of spores, biochemical properties and neutralization of their lecithinase by anti-C. perfringens alpha toxin antiserum. In addition, the usefulness of RapID ANA (AMUCO) and ANIDENT (API) kits for the identification of C. absonum was examined. The results were summarized as follows: 1. C. absonum isolates from clinical specimens were resistant against heating at 70 degrees C for 10 min and a type strain against heating at 85 degrees C for 10 min, less resistant than those of C. perfringens BP6K. 2. C. absonum differentiated from C. perfringens in fermentation of trehalose, melibiose and raffinose, and hydrosis of esculin and starch. 3. Lecithinase of C. absonum was not completely neutralized by anti-C. perfringens alpha toxin antiserum. 4. Both RapID ANA and ANIDENT kits were useful for differentiation of C. absonum from C. perfringens but not for the identification of C. absonum. PMID- 1624819 TI - [Tsutsugamushi disease found in Haruna District, Gunma Prefecture--evaluations of the clinical features and the outbreak pattern]. AB - From November to December in 1990, 7 cases of tsutsugamushi disease were found first in the southern foot of Mt. Haruna of Gunma Pref., Japan. The present study was conducted to clarify the clinical features and the outbreak pattern of rickettsial infection in this area. All the patients consisting of 6 males and 1 female farmers were admitted to our hospital, complaining of high fever, chills and skin rash on 5-12 days after working in the field. Based on laboratory examinations and one (or two) typical eschar, a tentative diagnosis of tsutsugamushi disease was made and all patients became better soon after the therapy with intravenous administration of minocyclin (200 mg/day). The high titer of serum antibody to Karp type Rickettsia (Orientia?) tsustugamushi was detected by an immunoperoxidase test (IP) in most of the patients, and also a Karp-like strain was isolated from only one patient, probably due to low virulence to mice. The agricultural areas along the Agatuma and Nakuta rivers in the northern foot of Mt. Haruna have been well known as the most endemic foci of the disease in Gunma Pref. Nevertheless, it was suggested that outbreaks of the disease might be potentially wide-spread throughout this Pref., when the prevalences of the disease were evaluated as incidences to a hundred thousand inhabitants or adjusted by the density of agricultural populations of each administrative divisions. As most of the patients in Gunma Pref. have been officially reported in autumn, a statistical trial indicates that there is a significant correlation between the levels of temperature and outbreaks of the disease in autumn.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1624820 TI - Seroepidemiology status of Nepalese against hemolytic streptococcal infection in Katmandu. AB - Immune status of apparently healthy Nepalese against hemolytic streptococci was studied by measuring antibodies to various streptococcal antigens such as streptolysin-O (SO), streptokinase (SK), deoxyribonuclease-B (DN-B) and streptococcal polysaccharide (SP). The normal range of anti-streptolysin-O (ASO), anti-streptokinase (ASK), anti-deoxyribonuclease-B (ADN-B) and anti-Streptococcus polysaccharide (ASP) was 60-480 (T.U.), 40-1024 (titer), 60-1280 (titer) and less than 2-128 (Unit), respectively. No difference was observed between the two sexes. ASO and ADN-B were measured by the neutralization method. Passive hemagglutination (PHA) was used to measure ASK and ASP. These values were 2-3 fold higher than those obtained on the Japanese subjects. PMID- 1624821 TI - [Serovar distribution and drug resistance of Salmonella isolated from imported and domestic cases in 1980-1989 in Tokyo]. AB - A total of 6,816 strains of nontyphoidal Salmonella isolated from oversea travellers (imported cases) and domestic healthy individuals and sporadic cases (domestic cases) in Tokyo from 1980 to 1989 were studied for their serovar distribution and antimicrobial sensitivity. The serological typing results showed that the Salmonella strains were classified into 22 O groups and 156 serovars. Among serovars identified, S. ser. Anatum, S. ser. Derby, S. ser. Blockley, S. ser. Agona and S. ser. Typhimurium were predominant in imported cases, while S. ser. Litchfield, S. ser. Typhimurium, S. ser. Hadar, S. ser. Infantis and S. ser. Thompson were predominant in domestic cases. It was also noticed that isolation rates of S. ser. Hadar and S. ser. Blockley have tended to increase noticeably in recent years in both cases. From antimicrobial sensitivity testing, 739 (28.1%) of 2,628 strains isolated from imported cases and 1,047 (25.0%) of 4,188 strains isolated from domestic cases were found to be resistant to any one of the drugs tested (CP, TC, SM, KM, ABPC, ST, NA, FOM and NFLX). From 1980 to 1983 the resistance rate was less than 20% for both cases and then the rate was increased year by year, and it became greater than 40% in 1989. Serovars of a high resistant rate during this period were S. ser. Hadar (96.3%), S. ser. Blockley (92.0%), S. ser. Typhimurium (75.7%), S. ser. Kentuckey (64.1%), S. ser. Krefeld (59.3%), and S. ser. Panama (58.3%) for the imported cases and S. ser. Hadar (97.5%), S. ser. Blockley (57.4%), S. ser. Litchfield (44.6%), S. ser. Enteritidis (44.4%), S. ser. Muenchen (42.2%) and S. ser. Typhimurium (40.9%) for the domestic cases. Drug resistance patterns of the resistant isolates varied up to as much as 50 patterns. Prevalent patterns recognized were TC.SM, CP.TC.SM.KM, TC, CP.TC.SM.KM.ABPC and SM for imported cases and TC.SM, TC, TC.SM.KM, SM, and CP.TC for the domestic cases. 21(12.4%) of 170 drug resistant strains were isolated from imported cases from 1988 to 1989 were found to have conjugative transmissible R plasmids. PMID- 1624822 TI - [Serological studies on Campylobacter jejuni/coli: establishment of national reference system for serological typing in Japan]. AB - In order to establish a national reference system for Campylobacter serotyping in Japan, 7 local institutes of public health collaborated to prepare 30 serogrouping antisera including 26 antisera of Lior's serogrouping system and 4 antisera of TCK serogrouping system which was developed by the Tokyo Metropolitan Research Laboratory of Public Health. A total of 603 strains (92.2%) out of 654 isolates from 23 outbreaks of C. jejuni throughout Japan were serogrouped by the 30 antisera. Out of 1,198 strain isolated from sporadic cases of Camplyobacter gastroenteritis, 883 (73.7%) were typed and 298 strains (24.9%) were untypable. The remaining 17 strains belong to rough form were not used for serogrouping. A hundred thirteen out of 883 strains have reacted with more than one typing serum. Among C. jejuni isolated from 7 prefecture, Lior's serogroup 4 was most common followed by Lior's serogroup 4, 2, 11, 1 and TCK serogroup 1 and 12. We conclude from the experiment described above that this Lior's serogrouping system by combining with TCK serogroup for Campylobacter jejuni/coli is useful in epidemiological investigations in Japan. PMID- 1624823 TI - [Contamination of endoscopes and endoscope washers by atypical mycobacteria]. AB - Contamination of endoscopes and endoscope washers by atypical mycobacteria was studied. Large amounts of atypical mycobacteria were detected with high frequency inside endoscopes and endoscope washers. The species of atypical mycobacteria was Mycobacterium chelonae subsp. abscessus. Antibacterial-effects of glutaraldehyde against isolated atypical mycobacteria were checked. Sufficient antibacterial effect was not obtained by 2% glutaraldehyde solution for endoscope sterilization. However, after frequent manual washing and brushing of endoscopes, by using 3% glutaraldehyde solution and 70% alcohol, all endoscopic instruments were completely decontaminated. We must pay attention to contamination of endoscopes and endoscope washer at least once a month. PMID- 1624825 TI - [An outbreak of Pseudomonas folliculitis in children--the first report on Pseudomonas folliculitis in Japan]. AB - An outbreak of Pseudomonas aeruginosa folliculitis in 6 children occurred within 5 days after playing in a tiny vinyl pool. The follicular macular or pustular eruptions were mainly distributed on the trunk. No associated symptoms were seen. The causative Pseudomonas aeruginosa strain isolated from pustules of one case belonged to serogroup E, corresponding to O-11 (Difco). The rash subsided promptly and spontaneously. Furthermore, we have encountered another case of Psedomonas folliculitis caused by P. aeruginosa serogroup G, corresponding to O-6 (Difco). The maculopustular rash was distributed on the trunk and disappeared spontaneously as the cases mentioned above. The folliculitis of this baby were probably associated with the repeated use of family bath without changing water. In U.S. and Europe Pseudomonas folliculitis have been reported very frequently, but our cases were reported for the first time in Japan. PMID- 1624824 TI - [Long term eradication rate of mebendazole therapy for strongyloidiasis]. AB - We treated 245 strongyloidiasis patients with 7 schedules of mebendazole (MBZ) and obtained the eradication rates at 8 months to 2 years after the final treatment as described follows; MBZ (100 mg) was given twice a day orally. [Square bracket shows incidence of liver disfunction.] 1) The eradication rates at 2 years after single course of MBZ therapy for 28 days and a combination therapy (thiabendazole 500 mg powder form three times daily for 5 days followed by MBZ in powder form for 9 days, repeated once) were 93.8% (15 of 16 patients), [71.4%] and 100.0% (16/16), [50.0%]. 2) The eradication rates at 8-15 months after using MBZ alone in varying dosages were as follows: a) MBZ powder was administered for 5 days and was then repeated 1, 3 and 4 weeks later: 87.1 (27/31), [51.1%]. b) MBZ powder was given for 5 days and repeated 1 and 3 weeks later: 100.0% (7/7), [30.8%]. c) MBZ powder was administered for 4 days and repeated 1, 3 and 4 weeks later: 96.3% (26/27), [57.8%]. d) MBZ in tablet form was given for 4 days and repeated 1, 3 and 4 weeks later: 89.6% (43/48). [66.2%]. e) MBZ in tablet form was administered for 4 days and repeated 1 week later: 69.2% (9/13), [25.0%]. As described above, although the incidence of liver disfunction in the 4-day with 2-course therapy was lower than the other schedules, the eradication rate was lower. From these results, MBZ should be given to strongylodiasis patient for 4 days and repeated once, or for 3 days and repeated two or three times with 1 to 2 weeks intervals. PMID- 1624826 TI - [Evaluation of serological and biochemical diagnosis of candidemia]. AB - In order to compare 4 serological and biochemical diagnostic tests, HA-test (Candida-HA-test), Cand-Tec, D-arabinitol detective test and Fungal Index (F.I.) were carried out in a total of 8 patients with candidemia, 6 were diagnosed to have systemic candidosis and 2 transient fungemia due to colonized catheters. Rabbits were given venous injections of 1.0 x 10(6) CFU (1 ml) of living Candida albicans type A to study the 4 diagnostic methods by sequential blood culture. Prior to clinical administration of antimycotics the diagnostic methods produced almost the same positive ratios. After administration of antimycotics, the HA test became positive later than Cand-Tec or D-arabinitol because it detected antibodies in the serum, but its conversion to negative also tended to be slightly slower. Accordingly, the HA-test is considered to be useful for retrospective diagnosis of systemic candidosis. In Cand-Tec, D-arabinitol and F.I., the cases where reversion to normal was not achieved soon after therapy were intractable. In one case, the antigen values after therapy were four times as high as prior to treatment. To differentiate the two cases with transient fungemia from those with systemic candidosis HA- and D-arabinitol tests were considered to be superior to Cand-Tec and F.I. In the experiments with rabbits Cand-Tec was, in spite of its being positive in blood culture, always negative. PMID- 1624827 TI - [Effect of methylrosanilinium chloride to MRSA nasal carriers]. AB - Since the end of 1987, we have noticed an increasing incidence of Methicillin resistant Staphylococcus aureus (MRSA) among the inpatients of Yamanashi Medical College Hospital. MRSA strains were identified in 70-80 percent of the specimens obtained from patients with Staphylococcus aureus. From 1988 we performed yearly bacteriological examinations of the nares of medical personnel at Yamanashi Medical College Hospital. We treated nasal carriers with OFLX drop lotion or Povidone-iodine applied to the nares. In 1991 we treated eight nasal carriers, who had been unsuccessfully treated with Povidone-iodine, with 0.01% Methylrosanilinium Chloride ointment which was applied to the nares once a day for two weeks. A post-bacteriological examination again revealed that MRSA vanished from the nares of six nasal carriers. The minimum inhibitory concentration (MIC) of Methylrosanilinium Chloride was determined by the agar plate dilution method. The 100% MICs of MSSA were 1.0 microgram/ml and of MRSA were 1.0 microgram/ml by Methylrosanilinium Chloride. Moreover we examined the MICs of Methylrosanilinium Chloride against MRSA under the existing 5% Albumin, and consequently the 100% MICs were 4.0 micrograms/ml. Therefore a 0.01% Methylrosanilinium Chloride has sufficient efficacy against MRSA. The reaction of the skin and nasal mucosa to Methylrosanilinium Chloride was examined by using three groups of guinea pigs. 0.1% and 0.01% Methylrosanilinium Chloride ointment and hydrophylic poloid were applied to the nares and skin once a day for two weeks. Post-observation with an opticmicroscope revealed no significant findings. Methylrosanilinium Chloride shows good anti-Staphylococcus aureus ability. Further investigation is needed to determine if Methylrosanilinium Chloride has additional clinical application. PMID- 1624828 TI - [Colonization rates of Mobiluncus spp. in female lower genital tract and its relationship with bacterial vaginosis]. AB - To clarify the colonization rate of Mobiluncus spp., 889 specimens were collected from the vagina and 688 specimens from the cervical canal in three groups of women, namely, non-pregnant women, pregnant women, and patients fulfilling the criteria of bacterial vaginosis. On screening, this organism was detected from the vagina in 18/576 cases (3.2%) in non-pregnant women and in 2/280 cases (0.7%) in pregnant women, and it was detected from the cervical canal in 12/410 cases (2.9%) in non-pregnant women, and 3/278 (1.1%) in pregnant women. Although the positive rates were slightly higher in non-pregnant women from both the vagina and cervical canal, they were not significant. However, in cases of bacterial vaginosis, the positive rate of Mobiluncus spp. was 9/33 cases (27.3%), so that it was significantly higher than in the other two groups. Although the role of Mobiluncus spp. in bacterial vaginosis has not been clarified, our results indicate that the presence of Mobiluncus spp. is abnormal, since its colonization rate in healthy women is too small to be regarded as a member of normal flora. G. vaqinalis and anaerobes (other than Mobiluncus spp.) are also closely connected to bacterial vaginosis. G. vaginalis alone was seen in 7/33 cases (21.3%), anaerobes alone in 7/33 (21.3%), and Mobiluncus spp. alone in 3/33 cases (9.1%). Multiple infections including 2 or 3 of the above organisms were seen in 13/33 cases (39.3%), and all cases had anaerobes. On the other band, only three cases were infected by none of the above organisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1624829 TI - [Evaluation of micro particle enzyme immunoassay (MEIA) for the demonstration of antibody to hepatitis B surface antigen]. AB - A fully automated microparticle enzyme immunoassay (IMx AUSAB, Abbott) has been recently introduced for the detection of the presence of antibody to hepatitis B surface antigen (anti-HBs). The present trial was carried out to determine the feasibility of using the IMx AUSAB with sera and plasma, and for comparison with RIA (AUSAB, Abbott) and EIA (AUSAB EIA, Abbott). According to the kinds of vaccines used and locations of residents, the subjects were divided into six groups. Results obtained were as follows; In the test of 642 sera from 446 vaccines and 196 other inhabitants of Okinawa and Miyazaki prefectures, 388 (87.0%) were found positive for anti-HBs using IMx, 392 (87.9%) with RIA and 359 (80.5%) with EIA. Among those vaccinated with recombinant vaccines, 96.6% were found positive with IMx, 96.2% with RIA and 89.4% with EIA. Among subject vaccinated with plasma derived vaccines, 72.9% were found positive with IMx, 75.7% with RIA, and 68.5% EIA. Quantitative agreement between IMx and RIA among the six groups gave linear correlation coefficients ranging from 0.459 to 0.821. In the group vaccinated with the recombinant vaccine by K company (r = 0.459), anti-HBs was confirmed in many sera by IMx compared to that confirmed by RIA and EIA. In addition, anti-HBs was assayed within one hour by IMx and the procedure was simplified by autoanalyser equipped for this method. The results indicate that the sensitivity of IMx is equal to that of RIA and more than that of EIA, and that quantitative linear correlations were obtained between IMx and RIA, and IMx and EIA. PMID- 1624830 TI - [A clinical study of respiratory tract infection due to Staphylococcus aureus detected by transtracheal aspiration]. AB - A clinical study of 24 patients with respiratory tract infection due to S. aureus detected by transtracheal aspiration (TTA) was conducted, and the following results were obtained. 1) The detection frequency of S. aureus was relatively low (4.6%). 2) Pneumonia was the principal clinical manifestation. 3) Approximately one half of the patients had previously received antimicrobials. 4) Multiple organisms were frequently detected, particularly in cases of hospital-acquired infection. H. influenzae was the most frequently simultaneously detected organism. 5) On sputum examination, approximately 20 ml of purulent sputum was found in most cases, and S. aureus was detected in sputum specimens from 20 of the patients. 6) The largest number of cases was found in 1987. Onset was most common from autumn to spring. 7) Undernutrition was the most frequently associated host factor. As indicated by the above findings, the clinical expression of S. aureus infection is variable, and it is important that it be diagnosed accurately. PMID- 1624831 TI - [The study of pathogenic mechanisms of chronic Pseudomonas aeruginosa lung infections by mucoid strains]. AB - Chronic Pseudomonas aeruginosa lung infection with mucoid strains is the predominant cause of death in cystic fibrosis (CF) or diffuse panbronchiolitis (DPB). This infection is characterized by a chronic course without spread of the bacteria to the blood when compared with other infections due to the non-mucoid strains. However, the mechanism of P. aeruginosa lung infection with the mucoid strains remains obscure. Intra-tracheal and systemic infection in mice, susceptibility to the bactericidal activity of fresh human and mouse serum, and adherent activity to mouse fetal lung cell were examined for mucoid and non mucoid strains of P. aeruginosa. After intra-tracheal infection, the mucoid strains were distributed to other organs anormously but not the non-mucoid stains, and the bacterial number of the mucoid strains in the blood were significantly lower than that of the non-mucoid strains. On the other hand, when these strains were inoculated into the tail vein of mouse, the mucoid strain was eliminated more rapidly from blood as compared with the non-mucoid strain. The mucoid strains showed reduced bacteremic virulence when compared with non-mucoid strains with a 50% lethal dose (LD50) of 1.5 x 10(7) CFU/mouse as the mean value in a systemic infection. In contrast to the non-mucoid strains, the mucoid strains were sensitive to human fresh serum but were resistant to mouse fresh serum. The mucoid strains adhered to the monolayer of the mouse fetal lung cell 7 fold better than did non-mucoid strains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1624832 TI - Abscess formation complicated in ovarian mucinous cystadenoma: a case report. PMID- 1624833 TI - [Pneumonia caused by Moraxella subgenus Moraxella sp]. AB - Moraxella subgenus Moraxella sp. was isolated in pure culture from the sputum of a 43-year-old male with pneumonia and congestive heart failure due to idiopathic dilated cardiomyopathy. In this case, we concluded that the patient's bacterial pneumonia was caused by M. (M.) sp. based on a Gram stain of the sputum smear and bacterial findings, increased WBC count, and elevated CRP. A chest X-ray revealed right middle, and left upper and middle lobe infiltrates. This Moraxella strain produced a BRO-type beta-lactamase, a carbenicillinase-type enzyme. PMID- 1624834 TI - [Epidemiological studies on viral hepatitis among long-term sojourners in the developing countries and evaluation of preventive measures]. AB - It is known that acute viral hepatitis is very common among sojourners in developing countries. In order to conduct effective health control, epidemiological studies were made on viral hepatitis which occurred among Japanese staying in developing countries, and evaluations were carried out on preventive measures. The subjects of present study were a group of Japanese people staying in developing countries for two years. Mid year population of the group was 1732 in 1988. Period of the present study is ten years from 1979 to 1988. The study was conducted based on the reports from offices in each country, survey trips and serological studies on the subjects. In 1979, frequency of hepatitis A (HA) was very high showing 79% of total hepatitides. However after starting of inoculation of human immune serum globulin (ISG), the frequency of HA declined remarkably. Statistical significance was recognized in the efficacy of ISG. Among 35 cases of hepatitis B (HB) (34 males and 1 female), 2 derived from HBe antigen carrier while the remaining 34 were regarded as infected during their stay in developing countries. No cases of HB were recognized among those who received injections of HB vaccine. The rate of people whose HB marker turned positive during their stay is showing a tendency of increase (4.2% in 1987). The frequency of infection with HB virus is especially high in Asian and African countries where the carrier rates of native people were also high. Ten cases of non-A non-B hepatitis were recognized. Among them 7 were infected in Asia, 1 in Africa and 1 in Central America.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1624835 TI - [Sero-diagnosis for human parvovirus B19 infection by IgM and IgG antibody capture method of enzyme-linked immunosorbent assay--study on an epidemic case of erythema infectiosum]. AB - The IgM and IgG antibody capture methods of the enzyme-linked immunosorbent assay (ELISA) for human parvovirus B19 were performed using Horseradish peroxidase (HRPO)-labeled anti B19 monoclonal antibody. Serially obtained serum samples from one erythema infectiosum (E.I.) patient were examined at once by this methods. The dOD values of the IgM and IgG antibodies decreased on the typical curves according to the course of recovery. In the epidemic case of E.I. among students of one nurse school, 1) The first patients was estimated by comparing the change of dOD values of sera obtained at end of the epidemic and 1.5 months later. 2) In the pre-existing antibody positive persons, the dOD values of IgG antibody did not changed during the epidemic. 3) After the E.I. epidemic, and approximately 30% of the students were remained uninfected. PMID- 1624836 TI - [Determination of the neutrophil chemotactic factor in bronchoalveolar lavage fluid in patients with diffuse panbronchiolitis]. AB - It is well known that erythromycin (EM) therapy is effective on chronic lower respiratory tract disease, including diffuse panbronchiolitis (DPB). In this study we investigated the relationship between clinical findings and neutrophil chemotactic activity (NCA) in bronchoalveolar lavage fluid (BALF) in patients with DPB receiving orally EM therapy. The NCA in post-EM therapy BALF was significantly reduced (p less than 0.001) compared with that in BALF before EM therapy (30.17 +/- 7.84% vs 53.05 +/- 10.65%). On the respiratory function before and after EM therapy, DPB patients (20 cases) showed significant improvement of %VC, FEV1.0, RV/TLC (p less than 0.001, each) and V25 (p less than 0.05). And on the post-EM therapy blood gas, PaO2 and AaDO2 level were confirmed to be significantly improved (p less than 0.001). In addition, we examined the correlation between the improvement ratio of clinical finding and the reduction of NCA in BALF after EM therapy in 10 patients with DPB. We found the significant correlation between the improvement ratio of PaO2 and the reduction NCA in BALF of those patients (p less than 0.05). There were no significant relationships between the improvement ratio in other parameters as stated above and the reduction of NCA in BALF. These findings indicate that EM restrains the NCA in BALF of patients with DPB and impairs the accumulation of neutrophils in respiratory tract, ultimately contributes to the improvement of clinical symptoms such as sputum and clinical findings such as PaO2 in patients with DPB. PMID- 1624837 TI - [Isolation of verocytotoxin-producing Escherichia coli from cattle and pets]. AB - During a three-year period (1987 & 1990), a comprehensive attempt was made to isolate verocytotoxin-producing Escherichia coli (VTEC) from 96 bovine, 89 porcine, 67 canine and 18 feline cases suffering from gastroenteritis. VTEC were isolated from 11 cows and 1 cat. Bead-ELISA and oligonucteotide probes were used to type the verotoxins (VT) and it was found that the VTEC strains from cows produced not only the currently recognized VT1, VT2 and VT2vh but also produced two new VT's tentatively designated as VTx and VTy. The strain from the cat produced VTy. Serotyping of the strains revealed that some animal strains belonged to similar serotypes as those isolated from human patients with hemorrhagic colitis and hemolytic uremic syndrome. Cattle, especially cows, and domestic pets apparently are reservoirs of VTEC and probable sources of infection in our country as has been previously documented in Canada and USA. PMID- 1624838 TI - [Rapid differentiation method for Shigella and Escherichia coli--application of Indole (tryptophanase), PGUA (beta-glucuronidase) and ONPG (beta-galactosidase) tests]. AB - For the differentiation of Shigella from Escherichia coli, Indole (tryptophanase), PGUA (beta-glucuronidase) and ONPG (beta-galactosidase) tests were used. A total of 377 Shigella and 124 E. coli strains was examined for each sero- and biosero-type by using these tests. The results were as follows. 1) There were no Shigella strains showing positive reactions for both Indole and ONPG tests. 2) No E. coli strains with Shigella-like characteristics (negative for lysine-decarboxylase, motility and lactose-fermentation tests) showed negative results for both Indole and PGUA tests. 3) The abovementioned strains were classified into twelve types according to the results of these tests. Shigella strains, thus, were differentiated from antigenically Shigella-like E. coli strains. Additional use of these tests together with the conventional methods may valuable for the identification of Shigella strains. PMID- 1624839 TI - [Molecular epidemiological study on Escherichia coli O114 by DNA analyses]. AB - Four strains of Escherichia coli O114:non-motile (NM) were isolated from patients supposed to have endemic diarrhea in 1989. The plasmid DNA profiles and restriction fragment patterns of chromosomal DNA digested with Not I analysed by pulsed-field gel electrophoresis (PFGE) of E. coli O114:NM strains were compared with those of other 9 strains of E. coli O114 isolated elsewhere (O114:H2, 1 strain; O114:H4, 2 strains; O114:H9, 2 strains; O114:H10, 1 strain; O114:H11, 1 strain; O114:H21, 1 strain; O114:H32, 1 strain). All of E. coli O114:NM strains showed the same plasmid DNA profile and chromosomal DNA fragment patterns. The strains of E. coli O114:NM and O114:H11, and O114:H21 and O114:H32 showed the same plasmid DNA profiles, respectively. On the other hand, these strains could be differentiated by the chromosomal DNA fingerprint patterns. The chromosomal DNA fragment pattern of all E. coli O114:NM strains is completely different from those of the other 9 control strains. We suggest that chromosomal DNA fingerprinting is useful for the epidemiological study of E. coli O114 associated endemic diarrhea. PMID- 1624840 TI - Isolation rates and pathogenicity of enterococci in obstetric and gynecological operations. AB - Isolation of enterococci in patients undergoing obstetric and gynecological operations was studied as well as reviewing the postoperative infection due to this organism during the period from 1985 to 1990. 1) In 126 cases undergoing abdominal total hysterectomy, vaginal specimens were obtained before and after (3rd day) the operation. The isolation rates increased after the operation (before 16.7%, after 35.7%). They increased not only in the group using PIPC, CEZ, CEPR, CMZ, and LMOX by drip infusion but also in the group without prophylactic use of antibiotics. On the other hand in the group using CP vaginal suppositories, the isolation rate decreased. However no statistical proof was obtained as to antibiotics especially in regard to cephem drugs as the reason for the increase. 2) Enterococci were isolated from the surgical field during abdominal total hysterectomy in only 2.0% (n = 88). 3) Isolation rates of enterococci inside the transvaginal drain following radical hysterectomy (n = 30) reached 86.7%. 4) E. faecalis was isolated in 20.0% of the cases with wound infection (n = 25). However isolated Enterococcus strains were not regarded to be the causative organism. 5) There was one case of postoperative enterococcal septicemia in treating stage Ib adenocarcinoma of the uterine cervix. PMID- 1624841 TI - [Isolation of Chlamydia pneumoniae and antibodies to the agent in patients with acute bronchitis]. AB - Isolation of Chlamydia pneumoniae and serologic tests were performed on 85 children and adults patients with acute bronchitis admitted to the Kitasato Institute Hospital from January 1989 to May 1991. C. pneumoniae was isolated from sputa or tonsillar swabs in 11 of 57 (19%) patients examined. Of these, 10 patients were tested serologically and 9 (90%) had 16 or higher titer of IgG antibody. A total of 68 patients were tested serologically, and 17 (25%) revealed positive; 14 had a fourfold rise or more in the titer of IgG antibody, or IgM titer of 16 or more, and 3 had IgG antibody with a titer of 512 or greater. In 34 patients, sera were tested for evidence of acute infections not only with C. pneumoniae, but also with Mycoplasma pneumoniae, influenza A virus, influenza B virus, adenovirus, respiratory syncytial virus, coxackie A9 virus, parainfluenza virus type I, II, and III. Two of the 34 patients were associated with influenza A virus, 4 with influenza B virus, whereas 6 were associated with C. pneumoniae. The data available suggest that C. pneumoniae cause bronchitis much more than has been suspected, and also confirm earlier suggestions that the agent played an important role in respiratory tract infections. Chlamydia trachomatis was recovered from sputa and tonsillar swabs in 6 adults patients with acute bronchitis. Studies are needed for a better understanding of the epidemiology and clinical relevance of this microorganism to lower respiratory tract diseases in adults. PMID- 1624842 TI - [The ultrastructural study on the relationship between Chlamydia trachomatis and the host cell in adhesion and during and after invasion]. AB - Chlamydia trachomatis (C. trachomatis) is 0.4-0.5 microns in diameter in the EB stage, with the nucleoid located eccentrically within it. We studied the relationship between the eccentric nucleoid and the host cell surface under electron microscope, when C. trachomatis was in adhesion to the host cell and during and after invasion into the host cell. When C. trachomatis adheres to and invades a host cell, the eccentric nucleoid is located on the side distant from the host cell surface (44 of 66, 66%). The 1 x 3 chi-square test indicates that the difference is significant at p less than 0.001. After C. trachomatis invades a host cell, the eccentric nucleoid is located on the side close to the host cell surface (61 of 138, 44%). The 1 x 3 chi-square test shows the difference to be significant at p less than 0.001. However, since the latter (44%) is less than the former (66%). C. trachomatis revolves between adhesion and the completion of the invasion. The 2 x 3 chi-square test shows a significant difference at p less than 0.001. PMID- 1624843 TI - [Detection of rubella virus antibody by enzyme linked immunosorbent assay with parallel line method]. AB - An attempt was made to measure the antibody to rubella virus in human sera by ELISA by calculating the relative potency by the method of the parallel line assay. As a standard serum, adult serum 8 months after rubella infection was used. Sample sera were collected from 42 infants before MMR vaccination and 8-10 weeks after the vaccination and 48 adults three years or more after rubella vaccination. In addition, three infant sera with rubella 6-19 days after onset of rash and three gamma immunoglobulin products were used. The dose response curve of the standard serum and that of the sample serum showed the lineality and the regression line of the sample serum was parallel to that of the standard serum. And the relative potency of sample sera was successfully calculated. The good correlation was observed between the rubella antibody titer by hemagglutination inhibition test and that measured by ELISA. The coefficients of variance of relative potency obtained from four repeated measurements for two weeks showed from 15% to 25% in four sera of HI high titer. The reproducibility of parallel line assay was also satisfactory. PMID- 1624844 TI - [Shigella flexneri strains having a new type antigen]. AB - Five Shigella strains isolated from stool cultures of two domestic dysentery cases and three imported cases in Tokyo in 1986-1989 had an atypial serotype that agglutinated with only antiserum to S. flexneri group 6 factor antigen. These strains showed typical biochemical reactions of S. flexneri and were biochemically identical. Four of the strains were positive for Sereny test with guinea pig eye and the cell-invasion test with HeLa cells. The strains also had the virulence-plasmid encoding outer membrane proteins, indicating that these were pathogenic. These strains were serologically identical and gave significant cross-reactions with S. flexneri 1b and 4b that had group 6 factor antigen. However, results of reciprocal absorption tests showed that the O antigen of these strains were not identical to S. flexneri 1b and 4b, and were confirmed to have a new type antigen which can not be included among the known S. flexneri type antigen I-VI. Strain 88-893 is designated as the test strain for this new type antigen of S. flexneri. PMID- 1624845 TI - [A case of penicillin-resistant pneumococcal pneumonia and penicillin-binding proteins of the clinical isolates]. AB - We experienced a case of a 68-year-old female with beta-lactam antibiotics including penicillin G (PCG) resistant pneumococcal pneumonia, leading to death during the treatment with ceftizoxime (CZX). We reported the clinical course and the mechanism of resistance of isolated bacteria. The present case is the first in Japan. Minimum inhibitory concentration (MIC) against Streptococcus pneumoniae 88031 isolated from the present case was 1.56 micrograms/ml in PCG and 6.25 micrograms/ml in CZX, showing PCG resistance. The isolate was no beta-lactamase production and serotype 23. The drug susceptibility in 34 strains of S. pneumoniae which were isolated as causative organism of respiratory infection in our department in 1988 was studied. PCG high resistant strain (PCG MIC greater than 1.56 micrograms/ml) was only observed in the isolated strain in the present case and PCG low sensitive strains (PCG MIC = 0.1-1.0 micrograms/ml) were observed in 3 strains (8.8%). The CZX resistance was observed only in the present case. The detection of penicillin-binding protein (PBP) and binding affinity of beta-lactam antibiotics were studied using PCG sensitive strain, S. pneumoniae type I (preserved strain PCG MIC = 0.05 micrograms/ml, CZX MIC = 0.1 micrograms/ml, CMX MIC = 0.025 micrograms/ml) and PCG resistant strain, S. pneumoniae 88031. The result obtained showed that PBP1a, detected in sensitive strain type I, was not detected in resistant strain 88031 and PBP1b was increased. The binding of 14C-PCG of PCG resistant strain to PBP1b showed lower affinity for CZX and CMX than PCG sensitive strain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1624846 TI - [Studies on the effect of combination of amphotericin B and flucytosine on Candida albicans by flow cytometry]. AB - The antifungal effects of amphotericin B (AMPH) and flucytosine (5-FC) on three strains of Candida albicans were studied by flow cytometry (FCM). When the IFM4954 and IFM4949 were treated with AMPH or 5-FC alone, cytograms of cell distribution changed at the concentration of 1/2 MIC, respectively. Next, the effect of combination of AMPH and 5-FC were examined. Cytogram of cell distribution of IFM4954 and IFM4949 changed under the combination of 1/4 MIC of AMPH and 1/4 MIC of 5-FC, namely a synergic effect was observed. In conclusion, FCM is a useful apparatus for analysis of the effect of antifungal agents. PMID- 1624847 TI - [Significance of antimicrobial activities testing of antimicrobial agents in human urine]. AB - In order to clarify the in vivo effect of the new quinolones in the urinary tract, we investigated the antimicrobial activities against Escherichia coli in the human urine. Human urine was prepared from a normal volunteer. After cations were removed by chelating resin, human urine was supplemented with 50, 100, or 500 micrograms of Mg2+ per ml using MgCl2 or 10, 50, or 150 micrograms of Ca2+ per ml using CaCl2. The pH of human urine was adjusted to 5.5, 7.0, or 8.0 with HCl or NaOH. Four clinical isolates of E. coli and E. coli NIHJ JC-2 were used. And antimicrobial activities of the new quinolones (norfloxacin, enoxacin, ofloxacin and ciprofloxacin) against these strains were measured using various urines as mediums. Antimicrobial activities of the new quinolones were reduced in the presence of high concentration of magnesium or low pH of urine. However, there was no influence of calcium concentration of urine on antimicrobial activities of the new quinolones. From these results, the component of the urine should be checked in the treatment of the patients with urinary tract infection. PMID- 1624849 TI - [A case of Candida albicans endocarditis with impaired lung function]. AB - A 53-year-old male was admitted to the hospital because of Candida albicans endocarditis. He had had a thoracoplasty due to pulmonary tuberculosis and showed severe restructive lung function. In 1987 and '89, trachiostomy was made because of respiratory failure. The patient was well until nine months earlier, when he consulted a physician because of fever. The investigations failed in finding the cause of the fever. He was administered antituberculosis agents and antiinflammatory drugs but had a fever every day. Two months before admission, a cardiac ultrasonographic study showed evident vegetations with mitral regurgitation. From the above course and examinations, a diagnosis of Candida albicans endocarditis was made. Infusions of CEZ, TOB, PIPC and miconazole for more than one month was ineffective. In November, 1990, he was referred to our medical center for the purpose of operation. A blood culture proved Candida albicans infection. An intravenous administration of fluconazole 400 mg/day was begun. However, there was pulmonary bleeding probably due to heparin used for prevention of atrial thrombosis and he developed fever, hypoexemia, ventricular tachycardia, and hyponatremia. He underwent mitral-valve replacement with a SJM valve. Culture of the vegetated mitral valve again proved Candida albicans. After operation, hypoexemia, ventricular tachycardia, hyponatremia were improved gradually. However he had an eosinophilia, eruption, and dyspnea. We suspected a drug eruption of fluconazole. Lymphocyte stimulating test of fluconazole proved positive. After the episode, he had no symptoms and was discharged. PMID- 1624848 TI - [Single-dose treatment of tosufloxacin (TFLX) for acute uncomplicated cystitis]. AB - The effectiveness of a single 300-mg dose of tosufloxacin and of 3-day treatment with tosufloxacin (300 mg daily) were compared in a prospective trial in order to clarify the cost-effectiveness of tosufloxacin for acute uncomplicated cystitis. Fifty female patients (25 patients of each group) with acute uncomplicated cystitis received one of these treatment regimens, and the clinical data and follow-up culture results were analyzed. The effectiveness rates of single-dose treatment and 3-day treatment after 3 days were 100% and 96%, respectively. The recurrence rates of single-dose treatment and 3-day treatment after 14 or 28 days were 0% (0/13 patients) and 15% (2/13 patients), respectively. There was no significant difference in the effectiveness rate and the recurrence rate between these two groups, statistically. All isolated strains were eliminated in both regimens. From these results, it is suggested that single-dose treatment of tosufloxacin is effective enough for acute uncomplicated cystitis. PMID- 1624850 TI - Miliary aspergillosis in a patient with acute leukemia. PMID- 1624851 TI - Surgical treatment for ulnar nerve entrapment at the elbow. PMID- 1624852 TI - Subcutaneous or submuscular anterior transposition of the ulnar nerve? AB - Precise clinical and electroneurographic examinations were made of 51 patients before and after anterior transposition of the ulnar nerve. The mean follow-up period was 9.6 years. In 86%, hand function improved, while in 10% it remained unchanged. Subcutaneous transposition was better than submuscular transposition, especially with regard to sensation. This method is simple and involves low morbidity for patients. PMID- 1624853 TI - Simple decompression of the ulnar nerve: an alternative to anterior transposition. AB - Anterior transposition and/or medial epicondylectomy are often considered procedures of choice for ulnar neuropathy at the elbow. Much experience suggests simple decompression to be a comparably effective alternative which involves less trauma, morbidity, and rehabilitation time. The post-operative clinical and electrophysiological results of 52 cases of simple decompression (41 patients) are summarized. Excellent or good clinical results were found in 75% of the nerves. Mean ulnar motor conduction velocities were significantly improved post operatively, although nerve conduction parameters did not consistently correlate with clinical outcome. The average return-to-work time was 5.1 weeks. The advantages of simple decompression make it the procedure of choice for most cases of ulnar neuropathy. PMID- 1624855 TI - Specificity of muscle reinnervation following repair of the transected sciatic nerve. A comparative study of different repair techniques in the rat. AB - Specificity of muscle reinnervation and the recovery of muscle contractility were studied after repair of the transected rat sciatic nerve. Six different techniques were compared: epineurial suture, perineural suture, whole nerve graft, interfascicular grafts, skeletal muscle bridge and tubulization. Muscle tetanic force and specificity of reinnervation were evaluated 12 weeks after nerve repair. Recovery of tetanic force was superior after repair with epineurial sutures. There was no statistical significance between the other methods in respect of tetanic force. The specificity of muscle reinnervation was best after tubulization, repair with interfascicular grafts and perineurial suture. PMID- 1624854 TI - Medial epicondylectomy in cubital tunnel syndrome: an electrodiagnostic study. AB - Prospective analysis of 27 medial epicondylectomies in 22 patients with McGowan grade I ulnar neuropathy demonstrated an improvement in clinical symptoms. In all patients a N.C.V. study, in which compression of the ulnar nerve at the cubital tunnel was evident, has been a prerequisite for operation. Conduction velocity across the cubital tunnel averaged 48% of normal (26.4 +/- 8.7 metres per second) preoperatively and increased to 85% of normal (46.7 +/- 9.7 metres per second) postoperatively. A preoperative N.C.V. study allows the achievement of a high success rate, especially in the less well clinically defined group of patients with grade I neuropathy (subjective complaints without any objective signs of muscle atrophy). Medial epicondylectomy is safe and predictable in the treatment of cubital tunnel syndrome. PMID- 1624856 TI - Perineural pressures under the pneumatic tourniquet in the upper extremity. AB - The literature indicates that tourniquet-induced neurological injuries are relatively common and frequently occur at a subclinical level. In order to evaluate the pressure transmitted to the major peripheral nerves of the arm by an externally applied pneumatic tourniquet, a fully implantable biomedical pressure transducer was placed adjacent the radial, median and ulnar nerves in six cadaver upper extremities of average dimensions. This sensor allowed accurate, reproducible measurements of perineural pressures without requiring significant disruption of the normal anatomical structures of the test limb for its installation. At levels of tourniquet cuff inflation which are commonly used in clinical practice, there was little or no decrease in the pressure detected in the perineural regions over that applied to the surface of the limb. In addition, there was a steep gradient of perineural pressure between locations beneath the edge of the cuff and those under its midpoint. This was most marked at the highest levels of tourniquet inflation. At presently accepted levels of inflation, pneumatic tourniquet cuffs transmit high pressures to the peripheral nerves without any significant attenuation by the intervening soft tissues. The distribution of these forces is one which may subject the underlying nerves to deleterious shear forces, especially at higher levels of inflation. PMID- 1624857 TI - Anatomy of the extensor pollicis brevis muscle. AB - 52 hands have been dissected to check the anatomy and function of the extensor pollicis brevis. Various abnormalities were found: absence of the E.P.B. (two), insertion on the distal phalanx (four), absence of bony insertion on the base of the first phalanx and insertion on the extensor hood (36). In ten cases (in addition to the two with absence of E.P.B.), no function was elicited by pulling the tendon which inserted upon the extensor hood. PMID- 1624858 TI - Vibration-induced muscle injury. An experimental model and preliminary findings. AB - The hind paws of rats were subjected to vibration at a frequency of 80 Hz., an acceleration of 32 m./s.2 rms (i.e. ah.w approximately 6.3 m./s.2 rms) for five hours daily during five consecutive days. Morphological, histochemical and immunohistochemical analyses of the soleus, extensor digitorum longus and the plantar muscles in the vibrated limb and the contralateral control limb were performed. No changes were seen in the soleus or extensor digitorum longus muscles but different degrees of degeneration of the muscle fibres were seen in the plantar muscle sections as well as signs of regeneration. No changes were observed in the contralateral unexposed limb. It is concluded that it is not only nervous tissue but also muscle tissue that can be affected by vibration. The changes seem to be confined to muscles close to the vibration exciter. PMID- 1624859 TI - Intrinsic mitogenic potential of canine flexor tendons. AB - Recent studies have demonstrated an intrinsic neovascular response in intrasynovial healing tendons, introducing the possibility of mitogenic and/or angiogenic capability of intrasynovial tendon. To explore this hypothesis, healing canine flexor tendons were treated with early passive mobilization and the repair sites analysed at three, ten and 17 days. Specimens were mechanically digested and subjected to a standard BALB/c 3T3 mitogenic assay, which measures the capacity of tissue extracts to induce DNA synthesis and cell division in fibroblasts. Results revealed that both control and repaired flexor tendons possessed mitogenic activity, with the greatest activity observed in control specimens. Decreasing activity was noted as the time between repair and analysis increased. These data provide increasing evidence for the flexor tendon's active role in the healing process, and support the concept that mitogenic or growth promoting factors are associated with flexor tendons and may be released following injury, during the early stages of healing. PMID- 1624860 TI - Variation of holding strength of synthetic absorbable flexor tendon sutures with time. AB - This study examined the potential use of absorbable polytrimethylene carbonate (Maxon) sutures for tendon surgery. Flexor tendons of the third toe of 48 chickens were transected and sutured, then evaluated both mechanically and histologically at 0, five, 15 and 45 days after operation. Mechanical testing showed that the suture kept its strength long enough to unite tendon ends. However, high tissue reactivity of polytrimethylene carbonate during its dissolution caused adhesions. PMID- 1624861 TI - Biomechanical analysis of a step-cut technique for flexor tendon repair. AB - We compared the strength of a new step-cut technique for flexor tendon repair with that of the widely used Kessler-Tajima technique, giving special attention to the relative contributions of the core and epitendinous sutures. 36 flexor digitorum profundus tendons from human cadavers were used. Corresponding digits from the same donor were paired, and the two tendons of each pair were placed in the Kessler-Tajima and step-cut groups, respectively. Each group had three subcategories of repair: (1) core repair alone; (2) epitendinous repair alone; and (3) full repair. In the Kessler-Tajima repair, the core stitch contributed more to ultimate tensile strength, while the epitendinous stitch contributed more to gap formation resistance. In the step-cut repair, however, the epitendinous stitch contributed more to both measures of strength. The full step-cut repair was 65% stronger in resisting gap formation and had 84% more ultimate tensile strength than the full Kessler-Tajima repair. We attribute the greater strength of the step-cut repair to the additional number of epitendinous loops, which lie perpendicular to the long axis of the tendon. PMID- 1624862 TI - Scapho-lunate dissociation occurring with scaphoid fracture. AB - In the most widely accepted model of injuries to the carpus, scaphoid fracture and scapho-lunate dissociation are held to be mutually exclusive. Four cases in which they occurred together are reported, and the likely mechanism proposed. PMID- 1624863 TI - Twenty questions about scaphoid fractures. PMID- 1624864 TI - Trans-carpal injuries associated with distal radial fractures in children: a series of three cases. AB - Isolated trans-carpal injuries in children are rare. This paper presents three cases of trans-carpal injury associated with an ipsilateral distal radial fracture. Two cases involved simultaneous fractures of the scaphoid and the capitate. The third case involved the scaphoid and the triquetrum. The full extent of these injuries was not recognized on the initial X-rays. If a child presents with a displaced fracture of one carpal bone it may not be an isolated injury. PMID- 1624865 TI - Normal palmar tilt: is dorsal tilting really normal? PMID- 1624866 TI - Features of algodystrophy ten years after Colles' fracture. AB - The long-term outcome of algodystrophy is unknown. Ten years after Colles' fracture, 26% of 55 cases showed features of the syndrome. The finding of poor finger function three months following the fracture correlated significantly with the presence of components of algodystrophy after ten years. PMID- 1624867 TI - The "S" Quattro in the management of fractures in the hand. AB - The "S" Quattro has shown its value in the management of displaced comminuted intra-articular phalangeal fracture dislocations. Since then the system has been used as a dynamic flexible external fixator in the treatment of five maluniting phalangeal fractures, five comminuted condylar and four severe compound fractures. These challenging fractures have been dealt with by easy operations, taking full advantage of the versatility of the "S" Quattro to achieve good results. PMID- 1624868 TI - The conservative management of proximal phalangeal fractures of the hand in an accident and emergency department. AB - 147 proximal phalangeal fractures of the hand were managed by Accident and Emergency doctors and hand surgeons. Most were treated conservatively with good results. Those treated in A. and E. were usually transverse or basal fractures of the shaft. Articular, oblique, comminuted and compound injuries were associated with greater morbidity and required specialist care. PMID- 1624869 TI - Irreducible distal phalangeal epiphyseal injuries. PMID- 1624870 TI - Conservative surgery in the management of rheumatoid disease of the hand and wrist. PMID- 1624871 TI - Rupture of the flexor carpi radialis tendon associated with scapho-trapezial osteoarthritis. AB - A case of rupture of the flexor carpi radialis tendon in association with scapho trapezial osteoarthritis is reported. The symptoms of pain and swelling contrast with the loss of function which characterizes rupture of other tendons in the hand and wrist. PMID- 1624872 TI - Pisiformectomy in young patients. AB - Pisotriquetral arthrosis in young patients is considered rare and the diagnosis may be difficult to distinguish from other ulno-carpal problems. 12 patients under 40 years of age (15 cases) who underwent pisiformectomy were reviewed at a mean of 41 months. Patients with a good history of trauma and a positive response to intra-articular local anaesthetic injection did well. Others with an indefinite history and bilateral symptoms did not do so well. Trispiral tomography is the radiological investigation of choice. PMID- 1624873 TI - Chromosomal abnormalities in Dupuytren's contracture and carpal tunnel syndrome. AB - The cytogenetics of cell cultures derived from Dupuytren's tissue, adjacent palmar fascia and palmar skin from patients undergoing fasciectomy have been examined and the results compared to cell cultures established from palmar fascia, flexor retinaculum and palmar skin of patients undergoing carpal tunnel decompression. Chromosomal abnormalities were detected in cell cultures from Dupuytren's tissue in eight of the nine patients studied. Clones of cells trisomic for chromosome 8 were found in five of the nine patients. Trisomy 8 was also present in two of five flexor retinaculum cultures from carpal tunnel syndrome cases. These findings in both Dupuytren's contracture and carpal tunnel syndrome suggest the presence of chromosomal instability in the palmar fascia. The significance of the chromosomal abnormalities is however unclear, but they indicate a possible common pathway in the onset of pathological fibrosis. PMID- 1624874 TI - The long-term results of enzymic fasciotomy. AB - We reviewed ten hands in nine patients who had enzymatic fasciotomy for Dupuytren's contracture, with an average follow-up of 6.5 years. While all patients were initially satisfied with the results, the disease recurred quite rapidly to pre-operative levels in seven patients over the subsequent two to three years. PMID- 1624875 TI - Reversal of digital vasospasm by glyceryl trinitrate patch. AB - Localized digital ischaemia following tourniquet deflation is an event producing considerable concern after surgical procedures on the hand, and is more common when severe pre-operative deformity has been radically corrected. We describe three such cases of digital ischaemia, occurring immediately after the release of severe flexion contractures of the digits. Our cases were treated successfully by the application of a proximal cutaneous glyceryl trinitrate patch, which produced prompt recovery of the circulation in the affected digits. We suggest that this simple technique has an important role as theraputically, and possibly also as a diagnostic aid, in the evaluation and management of the post-operative ischaemic digit prior to re-exploration being undertaken. PMID- 1624876 TI - A comparison of arterial and venous flaps. AB - The survival rate and elastic properties of the anterior abdominal skin flap in Sprague-Dawley rats were studied in three groups of animals. In group 1 where the flaps were supplied by a normal artery, arterial flaps (1A) had better survival rate and elastic properties than venous flaps (1B). In group 2, where the flaps were supplied by an artery with diminished perfusion pressure, the arterial flaps (2A) still had slightly better results than venous flaps (2B). However, in group 3 where the flaps were supplied by a vein, venous flaps (3B) had better results than arterial flaps (3A). PMID- 1624877 TI - Congenital palmar nail syndrome. AB - Two patients are described who have a congenital ectopic nail on the little finger associated with absent flexion in this finger. One patient was treated by surgical excision of the nail. PMID- 1624878 TI - Isolated flexor pollicis longus palsy in twin sisters treated by brachioradialis transfer. AB - Isolated paralysis of flexor pollicis longus is an uncommon variation of the anterior inter-osseous nerve compression syndrome. Two cases occurring in twin sisters were treated by brachioradialis tendon transfer when no recovery was evident after six months, with good results. Brachioradialis transfer is technically easy to perform, but complete mobilization of the tendon and muscle is necessary to achieve the desired excursion of the muscle-tendon unit. PMID- 1624879 TI - Correlation between temporal bone pneumatization, location of lateral sinus and length of the mastoid process. AB - The relationship between temporal bone pneumatization and the location of the lateral sinus and length of the mastoid process was investigated in 60 fresh frozen adult temporal bones, by plain X-rays, computed tomography and surgical dissection including otomicroscopic findings. Temporal bone pneumatization was classified as small, moderate and large. After drilling, the shortest distances between the middle fossa dura and mastoid tip representing the mastoid length and between the sigmoid sinus and posterior border of external auditory canal were measured and compared to the degree of pneumatization. The distances in the specimens with pathological eardrum and adhesions in the middle ear were compared to the ones without gross pathology. The length of mastoid process was significantly shorter in specimens with small pneumatization than those with large (Mann Whitney P less than 0.001). The specimens with a pathological eardrum and middle ear adhesions had a significantly shorter mastoid length than those without gross pathology. There was no significant difference between degree of pneumatization and the shortest distance between sigmoid sinus and external auditory canal (Mann Whitney P greater than 0.05). It is demonstrated that the 'under-developed' mastoid process can be a consequence of hampered pneumatization. PMID- 1624880 TI - Recovery of Chlamydia pneumoniae, in six patients with otitis media with effusion. AB - Six cases of otitis media with effusion associated with Chlamydia pneumoniae, a currently recognized respiratory tract pathogen, are presented. The organism was isolated from the middle ear fluids and serological evidence confirmed it as the infectious agent. The study population is small; however, these reports suggest C. pneumoniae as a causative agent of middle ear diseases. PMID- 1624881 TI - Endoscopic transcanal myringoplasty. AB - The role of the rigid endoscope has been evaluated in the management of 36 cases with dry central perforation of the tympanic membrane. The graft take rate was 91.7 per cent and the air-bone gap was closed to less than 10 dB in 83.3 per cent. The use of the rigid endoscope in the management of dry central perforation of the drum represented a significant advance in middle ear surgery. It is used, in correlation with manometry, to evaluate the tubal function before ear surgery and to treat hidden causes of tubal obstruction. It replaces the operating microscope in observation and surgery of the tympanic membrane perforation. It overcomes anatomical variations that hamper access to the entire tympanic membrane during ear surgery. It provides an extremely sharp image with high resolution. PMID- 1624882 TI - Management of posterior mesotympanic cholesteatoma. AB - Contrary to previous practice, the eradication of posterior mesotympanic cholesteatoma can frequently be achieved using a transcanal approach and without the need for more major surgery. For success, certain specific steps are necessary. These are described and the results reported. PMID- 1624883 TI - Criteria for hearing preservation in acoustic schwannoma surgery: the concept of useful hearing. AB - In the quest for hearing preservation in patients with acoustic schwannomas it is essential that surgeons do not lose sight of the concept of 'useful' hearing. There is an important difference between hearing preservation which pleases the surgeon and that which will be appreciated by the patient. Tumour size, pure tone audiogram average differences between ears and speech discrimination scores have been recorded in a series of 114 patients with unilateral acoustic schwannomas. Criteria for useful hearing are presented in terms of pure tone audiogram average difference and speech discrimination scores. There were 11 patients (10 per cent) with a speech discrimination score of 50 per cent or more, a pure tone audiogram average difference of 30 dB or better and a tumour size of no more than 2 cm. Only one patient (0.9 per cent) had a speech discrimination score of 50 per cent or more, a pure tone audiogram average difference of 20 dB or better and a tumour size of no more than 1 cm. It is concluded that hearing preservation techniques may be applicable to between 1 and 10 per cent of patients with unilateral acoustic schwannomas. PMID- 1624884 TI - Use of protein electrophoresis in the diagnosis of cerebrospinal fluid rhinorrhoea. AB - The diagnosis of CSF rhinorrhoea on clinical grounds alone can be difficult. We describe how the use of non-invasive electrophoretic analysis of nasal secretions for tau protein (asialotransferrin) helped in the management of cases where the existence of a CSF leak was in doubt. Patients were thus saved unnecessary invasive investigations or surgery. A modification of the method of analysis, which improves diagnostic accuracy, is described. PMID- 1624885 TI - Combined internal maxillary and anterior ethmoidal arterial occlusion: the treatment of choice in intractable epistaxis. AB - Whilst it is generally accepted that the standard management for anterior or benign epistaxis is either cautery or anterior nasal packing, that of posterior or intractable epistaxis remains controversial. Various modalities of treatment, ranging from posterior nasal packing to arterial ligation and embolization, have been advocated but none have been unanimously accepted as the treatment of choice. The purpose of this paper was to determine the efficacy of internal maxillary arterial ligation versus combined internal maxillary arterial ligation and anterior ethmoid arterial coagulation in intractable epistaxis. Over a six year period, from 1985 to 1990, 454 patients were admitted and treated for epistaxis. Forty-seven patients were diagnosed as having intractable epistaxis on the basis that the epistaxis failed to settle on anterior nasal packing. They were moved to the next step in management, which was combined anterior and posterior nasal packing. There were 30 failures, one was found to have choriocarcinoma of the maxilla, and was treated with cytotoxics, and the other 29 were moved to the next step, which was arterial ligation. Fifteen patients had internal maxillary arterial ligation, and 14 combined internal maxillary arterial ligation and anterior ethmoidal arterial coagulation. Large windows were created in both the anterior and posterior walls of the maxillary sinuses and all identifiable branches of the internal maxillary artery were dissected out carefully and two medium size ligating clips were placed over the main trunk, the sphenopalatine and the descending palatine branches. Single clips were placed on all other identifiable branches. Coagulation of the anterior ethmoidal artery was performed with a bipolar cautery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1624886 TI - Influence of the mode of preparation on the long-term efficacy of homologous costal cartilage implants. AB - Devitalized homologous costal cartilage is widely employed as an implant in the management of the saddle nose. The tissue response induced by the implant is a combination of enveloping fibrosis and implant resorption, which will probably, ultimately, be complete. We have studied the balance between resorption and fibrosis, following different modes of cartilage preparation, in the mouse. Homologous costal cartilage was devitalized by four common methods--irradiation, formalin, glutaraldehyde and alcohol. Segments of this cartilage were inserted at separate sites in the subcutaneous plain of the tail. These implants were harvested after one year for histology. Variations in the mode of cartilage devitalization, while inducing variations in the degree of the tissue response, did not influence the balance between fibrosis and resorption. Thus the long term maintenance of tissue bulk following homologous cartilage implantation is not influenced by the mode of preparation. Evidence suggests that the ultimate cosmetic results of autologous and homologous costal cartilage implantation would be much the same, and the use of homologous cartilage must be justified on other grounds. PMID- 1624887 TI - Leprosy of the larynx. AB - The result of a study conducted on 30 patients of lepromatous leprosy regarding laryngeal involvement is presented. The incidence of leprous laryngitis is 36.6 per cent in this part of India in lepromatous leprosy patients. Leprosy is long standing disease so laryngeal lesions developed gradually and may be asymptomatic in some cases while others have been found to have variety of clinical manifestation in form of congestion, infiltration, nodulation, thickening and fibrosis. Anti-leprosy chemotherapy is equally effective on these lesions. A screening survey of laryngeal pathology in such cases should be done periodically. PMID- 1624888 TI - Characteristics of Groningen tracheo-oesophageal speaking valves prior to insertion and after removal for failure. AB - The Groningen valve was first used in Sheffield in 1986 in a patient who underwent laryngectomy for malignant disease. Since then it has been the main tracheo-oesophageal prosthesis used on our Unit for speech rehabilitation post laryngectomy. This biflanged device inserted primarily or as a secondary procedure remains in situ until failure occurs either because of leakage or because increased effort is required to produce satisfactory phonation. This in vitro study we examined the differences between new valves prior to insertion and those removed for failure. The mean forward opening pressures were shown to be similar in the two populations but the mean forward resistances were increased in those valves which were defective (P less than 0.001). In addition the mean reverse opening pressure was found to be significantly lower in the defective valves when compared with their new counterparts (P less than 0.05). PMID- 1624889 TI - Milk nasendoscopy in the assessment of dysphagia. AB - The bedside assessment of dysphagia may be difficult, due to the inability to witness the act of swallowing directly. The milk test described in this paper gives a good assessment of swallowing, is cheap and easily portable and allows an instant decision to be made without recourse to special investigations. PMID- 1624890 TI - Endoscopic endonasal surgery of posterior choanal atresia. AB - The use of the rigid endoscope in the management of posterior choanal atresia represents a significant advancement in choanal surgery. It provides an extremely sharp image with a magnified overview. It enables the surgeon to see the tips of his instruments, so that the bone is removed safely under direct endoscopic vision. It allows assessment of the size of the opening, in comparison to the normal choana. It ensures greater precision in flap preservation. The technique is short in time and safe, with early recovery and short hospitalization. PMID- 1624891 TI - Audiological, vestibular and radiological abnormalities in Kallman's syndrome. AB - Kallman's syndrome is a multifaceted congenital disorder with predominantly endocrine abnormalities. We have characterized the associated mixed hearing loss and identified consistent radiological evidence of abnormal temporal bone anatomy. Abnormal labyrinthine morphology is accompanied by a complete absence of response to vestibular stimulation with caloric or rotational chair testing. The endocrine abnormalities are correctable and Kallman's syndrome is a diagnosis worthy of consideration when assessing children with congenital hearing loss. PMID- 1624893 TI - Augmentation rhinoplasty in nasal sarcoidosis. AB - We present a case of nasal deformity due to sarcoidosis. The surgical management is discussed. The risk of secondary involvement of implanted autologous cartilage by the disease is emphasized. For this reason an inert allograft (silastic) is recommended for augmentation in this group of patients. PMID- 1624892 TI - Bilateral acute mastoiditis complicated by lateral sinus thrombosis. AB - A case of bilateral mastoiditis with subperiosteal abscesses complicating acute otitis media in a two and a half year old girl is presented. Contrast enhanced computerized tomography confirmed the diagnosis of right lateral sinus thrombosis. The aetiology, diagnosis and management of these conditions are discussed. PMID- 1624894 TI - Radiation-induced antrochoanal fibrosarcoma. AB - Therapeutic radiation for malignant conditions is known to cause sarcomatous change in an irradiated field after a latent period; equally this change may occur following radiotherapy to benign conditions which may result in a more difficult management problem later. Radiotherapy to benign conditions should be reserved for use after failure of conventional surgery or other interventional techniques. PMID- 1624895 TI - Chordoma of the parapharyngeal space. AB - An unusual case of a chordoma of the parapharyngeal space is presented with no direct involvement of the axial skeleton. Diagnosis was confirmed with the aid of immunocytochemical tests. PMID- 1624896 TI - Clear cell neoplasm. AB - We are reporting four cases of clear cell neoplasm. Local infiltration and destruction was observed in one case while in a second case, originating in the sublingual gland, metastasis to the lymph nodes occurred. The behaviour of these neoplasms has prompted the suggestion that these tumours be designated carcinomas rather that noncommittally tumours or neoplasms (Batsakis and Regezzi, 1977). The histopathological characteristics of our four cases conform to those that have been articulated and believed to be the distinctive features of these tumours (Batsakis and Regezzi, 1977). It is hoped that ours and similar reports will be helpful towards clearing the diagnostic and taxonomic confusion regarding these tumours. PMID- 1624897 TI - Oesophageal foreign body: an unusual cause of respiratory symptoms in a three week-old baby. AB - Impaction of a foreign body in the oesophagus is common in children. If the event is not witnessed by an adult or the object is radiolucent the diagnosis is difficult as respiratory symptoms may predominate. We report a three-week-old child with respiratory symptoms who had both a respiratory syncytial virus infection and a radio-lucent oesophageal foreign body. This case is the youngest yet reported and serves as a remainder of the difficulties in the diagnosis of this important condition. PMID- 1624898 TI - Non-occupational recurrent bilateral pneumoparotitis in an adolescent. AB - This is a case report of recurrent bilateral parotid swelling with intraglandular gaseous bubbles in a 14-year-old boy, together with a review of the literature on this condition, which is usually called pneumoparotitis. The disorder has been reported as an occupational hazard in wind instrument players and glass-blowers and also as a rare non-occupational disease, mainly in adolescents and often associated with psychological problems. PMID- 1624899 TI - Ballooned trachea as a consequence of intubation. AB - A case of iatrogenic tracheal dilatation is presented. This potentially fatal complication of endotracheal intubation may escape early detection. It is well demonstrated by CT scanning. PMID- 1624900 TI - Granulomatous cutaneous T-cell lymphoma of the neck. AB - A case of cutaneous T-cell lymphoma is presented in which the diagnosis was obscured by a concomitant granulomatous infiltrate. A working diagnosis of tuberculosis delayed appropriate treatment for several months over which time rapid progression of the disease was seen. Inclusion of overlying skin in the repeat biopsies yielded the histological information to establish the correct diagnosis and there was rapid regression on completion of a course of radiotherapy. PMID- 1624901 TI - Cystic lymphangioma in the adult parotid. AB - Cystic lymphangioma is a congenital lesion which rarely presents in adult life and even less commonly arises within salivary tissue. We report the sudden appearance of a large cystic lymphangioma within the parotid gland of a young man and discuss the management of this rare condition. PMID- 1624902 TI - Necrotizing sialometaplasia. AB - Necrotizing sialometaplasia is a benign self-limiting disorder which can simulate malignancy. We report the third such case of nasal fossa involvement in the literature. The pathology of this condition is discussed. PMID- 1624903 TI - Malignant melanoma of the middle ear. PMID- 1624904 TI - The impact of research on the Tufts College Dental School: from Dean Marjerison to Dean Marshall-Day (1933-1958). PMID- 1624905 TI - Differential diagnosis and treatment planning for edentulous implant candidates. PMID- 1624906 TI - Porcelain fracture: causes, prevention, and repair techniques. PMID- 1624907 TI - A clinico-pathologic presentation. Cherubism. PMID- 1624908 TI - A clinico-pathologic presentation. Ameloblastic fibrous odontoma. PMID- 1624909 TI - Evaluation of the CO2 laser for endodontic root apex welding. AB - A low-wattage carbon dioxide laser was tested as a means of welding (sealing) the apices of unfilled, endodontically prepared teeth. Thirty-five teeth were filed and lased using a variety of power settings. Apical seals were examined microscopically, radiographically, and mechanically for complete welds. Accurately directed laser exposures of 15 or more watts with a 0.5 second duration will completely seal the apical openings of anterior teeth. The ideal treatment for endodontically compromised teeth has always been a completely sealed tooth apex. Usually amalgam, gutta-percha, or resin sealers are used after a lengthy and tedious preparation of the exposed root area. The carbon dioxide laser is designed for soft tissue dental surgery but is capable of melting enamel and dentin which recrystallizes in a dense solid as it cools (fig. 1). The laser, with its potential for accurately delivering a great quantity of energy to a small, exposed surface, appears to be an excellent tool for quick, direct sealing of open apices. This paper will investigate the practicality and best methods of spot welding root apices. PMID- 1624910 TI - Wrongful birth and birth injury claims: new risks for oral surgeons. PMID- 1624911 TI - Synthesis and secretion of low molecular weight cuticular proteins during heat shock in the tobacco hornworm, Manduca sexta. AB - In the tobacco hornworm, Manduca sexta, heat shock normally elicits synthesis of the classic heat-shock proteins. A 1-hr heat shock of 42 degrees C and above can also increase the relative synthesis of certain 12-18 kD proteins in the epidermis. These 12-18 kD proteins were identified as cuticular proteins for several reasons. Like cuticular proteins, they appear only in the epidermis. They can be precipitated from epidermal homogenates with an antiserum to larval cuticle. The same conditions that increased labeled 12-18 kD proteins in the epidermis also increased labeled 12-18 kD proteins in the cuticle. Some of the epidermal increase may result from a partial inhibition of secretion to the cuticle during 46 degrees C heat shock, causing abnormal accumulation in the epidermis. However, slight increases also occur at lower temperatures, which do not inhibit secretion detectably. Preliminary results also indicate that total quantities of at least one cuticular protein mRNA may increase during heat shock, either because of increased transcription or increased mRNA stability. PMID- 1624912 TI - Effects of short-term 17 beta-estradiol treatment on the properties of T4-binding proteins in the plasma of immature rainbow trout, Oncorhynchus mykiss. AB - To determine the effects of 17 beta-estradiol (E2) on the properties of the plasma proteins that bind L-thyroxine (T4) immature rainbow trout, Oncorhynchus mykiss, were injected intraperitoneally on days 0 and 3 with 0.5 mg E2-3 benzoate/100 g body weight, and plasma was sampled on days 4, 7, or 12. Control trout received peanut oil alone. E2 caused a small but significant decrease in the free T4 index. Saturation analysis on miniature G-25 Sephadex columns revealed at least two major T4-binding sites. Filtration on agarose Bio-gel A 1.5 also indicated two major T4-binding protein fractions with molecular weights of 150 and 55 kDa with a small proportion of T4 binding to a 1,500-kDa site presumed to be lipoprotein. Addition of unlabeled T4 displaced [125I]T4 from the 55-kDa site and unmasked an adjacent site of higher molecular weight. E2 increased the proportion of T4 bound to the low-affinity (150 kDa) site relative to that bound to the high-affinity (55 kDa) site, increased the level of protein associated with the 1,500-kDa site and its T4 binding, and also initiated the production of presumed vitellogenin (VTG), which bound a small amount of T4. It is concluded that the E2-induced depression in FT4 is caused by a shift in T4 binding between high-affinity and low-affinity sites, and also by binding of small amounts of T4 to presumed lipoprotein and VTG. PMID- 1624913 TI - Changes in growth hormone and prolactin messenger ribonucleic acid levels during seawater adaptation of amago salmon (Oncorhynchus rhodurus). AB - To examine the changes in secretion of growth hormone (GH) and prolactin (PRL) with reference to their osmoregulatory roles, changes in pituitary mRNA levels and plasma concentrations of these hormones were examined during seawater adaptation in silvery juveniles (smolts) and precociously mature males (dark parr) of amago salmon (Oncorhynchus rhodurus). Transfer to seawater increased plasma sodium levels in both smolts and dark parr. Smolts adjusted their plasma sodium to the level associated with seawater-adaptation (165 mEq/liter) within 3 days, whereas no adjustment was seen in dark parr; the latter failed to survive in seawater for more than 3 days. In smolts, plasma GH levels increased significantly 1 day after transfer, whereas there was no significant change in dark parr. An increase in GH mRNA levels was observed in smolts in association with increased plasma GH, whereas there was no change in dark parr. In contrast, a reduction in plasma PRL levels was consistently observed in both smolts and dark parr after transfer to seawater. However, there was no significant change in PRL mRNA levels in either smolts or dark parr. These results suggest that both gene expression and release of GH are activated by seawater transfer only in smolts with adequate seawater adaptability, whereas PRL gene expression is decreased after seawater transfer regardless of seawater adaptability. PMID- 1624914 TI - In vitro synthesis of oviductal secretory proteins by estrogen-treated ovariectomized gilts. AB - The objective of this study was to identify, characterize, and examine oviductal secretory proteins (OSP) synthesized de novo by whole oviduct (WO), ampulla (A), and isthmic (I) tissue from ovariectomized (OVX), corn oil (CO)-, estrogen (E)-, progesterone (P)-, and E + P-treated gilts. Oviducts were collected from OVX gilts after CO, E, P, or E + P treatment for 11 consecutive days and tissue was incubated with 3H-leucine (3H-leu). Rates of 3H-leu incorporation into nondialyzable macromolecules by WO explants were greater (P less than 0.01) with E- compared to CO-, P-, or E + P-treated gilts and greater (P less than 0.05) by A explants with E- compared to CO-, P-, or E + P-treated gilts. An effect of location was noted, with A having a greater (P less than 0.01) rate of incorporation than WO or I. Conditioned culture medium was analyzed by one (1D)- and two-dimensional (2D) sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) and fluorography. Analyses by 1D-SDS-PAGE revealed three major E-dependent bands (335,000, 100,000, and 80,000 M(r)) in WO and A, and one (335,000 M(r)) in the I. A 20,000 M(r) band found in A was inhibited by E, while a 60,000 M(r) band found in the A was induced by P. Analyses by 2D-SDS-PAGE resolved major E-dependent bands 2 (100,000 M(r)) and 3 (80,000 M(r)) into basic and acidic 100,000 M(r) proteins and a 75,000-85,000 M(r) protein (pI less than 4), respectively, found in WO and A, but not in I. A basic 20,000 M(r) protein and an acidic 45,000 M(r) complex, both found in A, were inhibited by E. Gel filtration of culture medium revealed a high M(r) fraction (greater than 2 x 10(6)) that was induced by E and was 6.8-fold greater in medium from A than from I. This study clearly demonstrates that 1) WO and A tissue from E-treated gilts de novo synthesize and secrete three major proteins (basic 100,000, acidic 100,000, and 75,000-85,000 M(r)); 2) these E-dependent proteins are not found in I or with other treatment; 3) several protein complexes synthesized by A are inhibited by E treatment; and 4) a high M(r) fraction, produced primarily in the A, is induced or amplified by E. PMID- 1624916 TI - Regenerative responses in cultured hindlimb stumps of larval Xenopus laevis. AB - The regenerative capacity of larval Xenopus laevis hindlimbs amputated through the tarsalia at different stages of development and explanted in vitro was tested. In the first experimental series hindlimb stumps from stage 53, 54, 55, and 57 larvae (according to Nieuwkoop and Faber, '56) were cultured in Leibovitz's L-15 medium supplemented with 10% FCS, and 0.04 U of insulin and 10( 8) mg of L-thyroxine per ml of medium. Results showed that the distal part of the limb stumps from stages 53, 54, and 55 formed a regeneration blastema composed of proliferating mesenchymal cells beneath a typical apical cap. No blastema was formed in the proximal part of the stump. In limb stumps from stage 57, a regeneration blastema did not form either in the proximal or in the distal part of the stump. In a second experimental series, hindlimb stumps from stage 55 larvae, denervated 5 days prior to amputation in order to eliminate any residual neurotrophic factor, were cultured in a simplified L-15 medium containing 2% FCS and lacking insulin and thyroxine. Results showed that also in these experimental conditions the stumps from stage 55 formed a conical regeneration blastema at the distal tip. The blastema cells duplicated their own DNA and divided. At the proximal extremity no regeneration blastema was formed. In the same culture medium, the stumps of larvae at stage 57 did not form a regeneration blastema.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1624915 TI - An aerodynamic valve in the avian primary bronchus. AB - The segmentum accelerans in geese is a constriction in the caudal end of the primary bronchus. Experimental evidence suggests that this part of the airway functions as an inspiratory aerodynamic valve, accelerating the incoming airstream past the ventrobronchial openings. The luminal diameter of the segmentum accelerans dilates in the presence of elevated CO2 levels, probably through relaxation of smooth muscle. Physiological control of the segmentum accelerans may permit inspiratory aerodynamic valving to be maintained throughout a wide range of ventilatory flows. PMID- 1624917 TI - Steroid hormone-induced male sex determination in an amniotic vertebrate. AB - In many reptiles, sex is determined by the temperature at which the eggs are incubated (i.e., temperature-dependent sex determination, or TSD). Past studies have shown that exogenous steroid hormones can override the effects of temperature and induce female sex determination. However, past attempts to induce male sex determination have consistently failed. In the present study, sex determination was studied in a turtle with TSD. By utilizing an incubation temperature regimen that resulted in approximately a 1:1 sex ratio in the control group, sex determination was shown to be sensitive to both exogenous androgen and estrogen treatments: androgen induced the production of male hatchlings, whereas estrogen induced the production of female hatchlings. This is the first report of an amniotic vertebrate in which an exogenous steroid hormone induces male sex determination. PMID- 1624918 TI - Immunoglobulin-containing cells in chick embryo urogenital tissues: a new site for early B lineage cells in endothermic vertebrates. AB - We have employed histological and immunofluorescent staining procedures in order to characterize the distribution of mu + B lineage cells in tissue sections prepared from developing chicken embryo urogenital tissues (UGTs) between 14 and 21 days of incubation. B lineage cells were observed in tissue sections prepared from developing UGTs, especially the mesonephros and its associated tissue, throughout the sample period. The highest densities of mu + B lineage cells were observed in tissue sections prepared from 18 day embryos. The mu + UGT cells were distributed singly and in clusters in subcapsular regions and within the peritubular interstitium of the mesonephros. These observations (1) are consistent with those which suggest nonbursal site(s) for origin of cells in B lineage, (2) may help account for the varying effects of embryonic caudectomy performed between the second and third days of incubation and surgical bursectomy performed close to hatching, (3) may help provide new insights on the effects of sex hormones on B cell development, and (4) suggest fundamental ontogenetic and phylogenetic similarities between developing vertebrate immune systems. PMID- 1624919 TI - The role of the adrenal glands in regulating onset of winter fur growth in mink (Mustela vison). AB - The role of the adrenal glands in regulating onset of winter fur growth in mink was investigated in long-term adrenalectomized animals. Bilateral adrenalectomy of adult female standard dark mink between June 23 and July 11, 1990, initiated onset of winter fur growth approximately 6 weeks earlier than controls. One month following completion of the winter fur growth in adrenalectomized mink, molting and growth of a new coat was observed. The type of pelage that grew as a result of the second growth wave was less dense than the normal summer or winter fur. However, this renewed hair growth suggests that adrenal hormones not only inhibit the onset of winter fur growth but also influence the duration of inactivity following each period of hair growth. Administration of deoxycorticosterone as a mineralocorticoid supplement had no effect on initiation of fur growth. It would appear that adrenal hormones are part of the mechanism through which photoperiod regulates fur growth in the mink. The identity of the adrenal hormones and their site of action is unknown. PMID- 1624920 TI - Clinical correlates of cerebral ventricular enlargement in schizophrenia. Further evidence for frontal lobe disease. AB - Numerous studies have shown evidence of cerebral ventricular enlargement in schizophrenia and its relationship to severity of clinical symptoms and psychosocial dysfunction. In this large prospective study, 88 noninstitutionalized DSM-III-R schizophrenic patients were administered a CT scan and rated for positive and negative symptomatology and premorbid adjustment. The CT scans from 14 healthy controls were used for comparison of cerebral ventricular measures. Patients had an enlarged ventricle to brain ratio of the anterior portion of the lateral ventricles, the frontal horns, compared with controls. Patients with larger frontal horns had more severe negative symptoms and poorer premorbid childhood adjustment. The area of the main body of the cerebral lateral ventricles, though not elevated in patients, was correlated with the total number of prior hospitalizations. These results support the hypothesis of a structural and functional "frontal" deficit in schizophrenia. PMID- 1624921 TI - Cerebral blood flow abnormalities in adults with infantile autism. AB - Structural brain abnormalities have recently been discovered using magnetic resonance imaging in infantile autism, a neurodevelopmental disorder of unknown etiology. However, functional neuroimaging studies in autism using positron emission tomography have had conflicting results and have not explained how the known structural brain abnormalities in autism act in a functioning brain to produce autistic behavior. Using a new technology, high-resolution brain single photon emission tomography, we studied and scanned four young adults with infantile autism and four age-matched controls using the labeled ligand 99mTc-D,L hexamethyl-propylene amine oxime (99mTc-HMPAO). Total brain perfusion was significantly decreased in autism subjects (range, 58% to 72% of controls, p less than or equal to .02). In addition to the globally decreased perfusion, the autism group also had regionally decreased flow in the right lateral temporal and right, left, and midfrontal lobes compared with controls (p less than or equal to .02, Mann-Whitney t-test). PMID- 1624922 TI - Neuropsychological and clinical correlates of murder and other forms of extreme violence in a forensic psychiatric population. AB - The neuropsychological and clinical correlates of extreme violence were examined retrospectively in young and older inpatients of a forensic psychiatric hospital. The young group exhibited significantly higher rates of both a learning disability and a history of childhood conduct disorder, whereas the older group had a significantly higher rate of psychosis. The older individuals charged with murder were also more likely to have acted alone and to have had an intimate relationship with the victim. These results suggest that age, specific clinical and neuropsychological variables, and the characteristics of the violent act may represent important variables for risk models of violence. PMID- 1624923 TI - Vulnerability-stress factors in development of posttraumatic stress disorder. AB - Log-linear chi 2 analyses were conducted to examine potential interactions between the presence of precrime axis I psychiatric diagnoses and differential levels of crime stress in association with posttraumatic stress disorder (PTSD) in a community sample of 295 female crime victims. High crime stress was defined as crime that included either perceived life threat, actual injury, or completed rape. Crime stress level was significantly associated with PTSD after the crime. Thirty-five percent of subjects with high crime stress exposure met criteria for PTSD, as opposed to 13% of those with low crime stress exposure. Precrime diagnosis was not associated with high crime stress exposure, indicating that this is not a vulnerability factor for exposure to crime characteristics associated with increased rates of PTSD. There were no significant independent associations between precrime axis I diagnoses and PTSD after the crime. However, a significant interaction was observed among crime stress level, precrime depression, and PTSD such that the rate of PTSD was substantially higher in association with precrime depression only in the high crime stress exposure group. Major findings are consistent with previous results implicating trauma exposure as the primary factor in development of PTSD. However, the results indicate that precrime depression may constitute a vulnerability factor for development of PTSD under conditions of high crime stress exposure. PMID- 1624924 TI - Negative parenting behavior, combat exposure, and PTSD symptom severity. Test of a person-event interaction model. AB - The "personal characteristics" and "extreme event" hypotheses have been proposed as alternative explanations for the development of posttraumatic stress disorder (PTSD) among combat veterans. The person-event interaction model attempts to integrate both perspectives by hypothesizing that premilitary individual vulnerability characteristics play a greater role in influencing risk of PTSD or PTSD symptom severity at lower than at higher levels of exposure to traumatic combat stressors. Focusing on a sample of 57 Vietnam veterans undergoing inpatient treatment for diagnosed PTSD, we assessed this model by examining interactions between negative parenting behaviors in childhood (e.g., inconsistent love) and degree of combat exposure in predicting PTSD symptom severity. Hierarchical regression analyses supported the model, indicating that the father's negative parenting behaviors were more predictive of PTSD symptom severity at relatively lower levels of combat exposure. Implications of the findings for further research on multivariate, interactional models of PTSD etiology among Vietnam combat veterans are discussed. PMID- 1624925 TI - Avoidance and intrusion in posttraumatic stress disorder. AB - Longitudinal data from 290 firefighters who had completed questionnaires 4, 11, and 29 months after exposure to a natural disaster were used to examine the role of intrusive and distressing memories in the etiology of posttraumatic stress disorder. At 42 months, all those who were at risk of having developed a psychiatric disorder (N = 113) and a randomly selected comparison group (N = 34) who had never developed symptoms were interviewed using the Diagnostic Interview Schedule. The intrusion subscale score of the Impact of Events Scale accounted solely for the etiological link between the disaster and posttraumatic disorders. Avoidance had no direct relationship with the onset of symptoms and appeared to be a defensive strategy to contain the distress generated by the re-experiencing of the disaster, indicating the importance of separating these phenomena from disorder mood and arousal in posttraumatic stress disorder. An information processing model was validated using three different data sets, which suggests its robustness. Using cross-lagged panel correlations, a bidirectional relationship was demonstrated between disorder and intrusive recollections, suggesting that the intensity of recurring memories of a traumatic experience is as indicative of a disturbance of mood and arousal as the exposure to the trauma. PMID- 1624926 TI - Testing the validity of the neurotic depression concept. AB - We applied an operational definition of neurotic depression to 185 hospitalized patients who met Feighner and DSM-III-R criteria for unipolar depression. Based on a systematic chart review, 37 patients met the criteria for neurotic depression. As a group, these patients differed from nonneurotics in symptoms, clinical course, outcome, and family history. The neurotic depressives were younger and more likely to identify precipitating factors. They were less likely to meet criteria for melancholia and to have delusions. They were more likely to be ill 3 years later and more likely to have familial alcoholism. These differences help to confirm the validity of the neurotic depression concept. PMID- 1624927 TI - The effects of carbamazepine on stuttering. AB - No pharmacological treatment protocol has proven generally useful for all patients who stutter. Various medications, behavior therapy, relaxation, suggestion, and social-based therapies have been used. For this drug treatment study, two groups of adult stutterers were followed in an 8-week open label protocol. All subjects had in the past received speech therapy; none had been treated previously with medication for stuttering. The first group (N = 12) received a maximum dose of 800 mg of carbamazepine; the second group (N = 8) received a maximum dose of 400 mg of carbamazepine. Each patient served as his or her own control. A series of systematic speech tests was given weekly to determine the variability of fluency for each subject. A statistically significant change occurred for a number of "expectancy to stutter" characteristics. Subjects felt that they stuttered less often while taking carbamazepine. Subjective effects began before medication and continued after patients discontinued the medication. Struggle characteristics also subjectively decreased. However, no objective improvement was found. No change was found in percentage of words stuttered, reading improvement, or improvement in spontaneous speech rate. Interrater reliability showed a correlation of .996. Three carbamazepine serum level therapeutic windows were inspected with negative results. Interestingly, naive listener ratings did show a statistically significant improvement on carbamazepine versus placebo. Future anecdotal reports of pharmacological improvement of stuttering should be subjected to rigorous objective testing before general acceptance. PMID- 1624928 TI - The PEH. A questionnaire to assess acknowledgment of psychiatric illness. AB - The aim of this research project was to develop an instrument to measure acknowledgment and denial of illness in hospitalized psychiatric patients. The investigators developed a 23-item, 4-point self report scale, the Patient's Experience of Hospitalization (PEH), and collected validity data from a sample of inpatients. A total of 29 subjects completed the PEH, the Marlowe-Crowne Social Desirability Inventory (MCSD), the MMPI, and a Global Assessment Scale (GAS) report. The patients' psychotherapists also provided GAS scores. Kuder Richardson split-half reliability and point biserial correlations of 18 items were adequate. The PEH total score correlated significantly and positively with the difference between the GAS scores assigned to the patient by the patient and by the therapist, with the patient's self-report GAS score, with MCSD scores and with the MMPI L and K scales, considered to assess crude and subtle defensive denial. Correlations with MMPI clinical scales (symptom reports) were negative, further supporting the idea of the PEH as a measure of denial. PMID- 1624929 TI - Psychopathology among Jewish Ethiopian immigrants to Israel. PMID- 1624930 TI - Symptoms in nonpatient southeast Asian refugees. PMID- 1624931 TI - A positive correlation between permissiveness of mesoderm to neural crest migration and early DRG growth. AB - The microenvironment created by grafting rostral somitic halves in place of normal somites leads to the formation of nonsegmented peripheral ganglia (Kalcheim and Teillet, 1989; Goldstein and Kalcheim, 1991) and is mitogenic for neural crest (NC) cells that become dorsal root ganglia (DRG) (Goldstein et al., 1990). We have now extended these studies by using three surgical manipulations to determine how additional mesodermal tissues affected DRG growth in chick embryos. The following experimental manipulations were performed: (1) unilateral deletion of epithelial somites, similar deletions followed by replacing the somites with (2) a three-dimensional collagen matrix, or (3) fragments of quail lateral plate mesoderm. When somites were absent or replaced by collagen matrix, ganglia were unsegmented, and their volumes were decreased by 21% and 12%, respectively, compared to contralateral intact DRG. In contrast, when lateral plate mesoderm was transplanted in place of somitic mesoderm, NC cells migrated into the grafted mesoderm and formed unsegmented DRG whose volumes were increased by 62.6% compared to the contralateral ganglia. These results suggest that although DRG precursors do not require sclerotome to begin migration and condensation processes, DRG size is modulated by the properties of the mesoderm. Permissiveness to migration is positively correlated with an increase in DRG volume. This volume increase observed in grafts of lateral plate mesoderm is likely to result from enhanced proliferation of neural crest progenitors, previously demonstrated for DRG cells in rostral somitic grafts. PMID- 1624932 TI - Expression of a novel nuclear protein is correlated with neuronal differentiation in vivo. AB - We report the production of a monoclonal antibody (MAb 526) that recognizes a novel, developmentally regulated nuclear protein expressed in neurons throughout the rat nervous system. Analysis of whole brain and cell nuclear extracts by SDS PAGE and immunoblotting determined that MAb 526 recognizes a single nuclear protein (np) of apparent molecular weight 42 kD, designated np526, as well as a slightly larger (ca. 44 kD) cytoplasmic protein. Light microscopic immunocytochemistry showed np526 to be present in neurons of all types throughout the central and peripheral nervous systems. Nuclei of both fibrous and protoplasmic astrocytes were also immunoreactive, but oligodendrocyte nuclei were negative. Positive, but highly variable immunocytochemical staining of nonneural cell nuclei in a variety of other tissues was also observed. Electron microscopic (EM) immunocytochemistry using pre-embedding peroxidase methods revealed that np526 is associated with euchromatin or with the edges of condensed chromatin bundles in neurons, indicating that it is likely to be a chromosomal protein. Most interestingly, the expression of np526 was found to be developmentally regulated in brain. Immunocytochemical analysis of the developing cerebral cortex from embryonic day (E) 16 to postnatal day (P) 4 and cerebellum from P4 to P18 revealed that np526 first appears in central neurons following the cessation of mitosis and that the intensity of nuclear staining increases during subsequent neuronal maturation. To our knowledge, np526 is the first presumptive chromosomal protein whose expression has been precisely correlated with the early postmitotic differentiation of mammalian neurons. PMID- 1624933 TI - Cholinergic differentiation in neurogenic basal forebrain cultures. AB - To study early events in the central nervous system (CNS) cholinergic development, cells from rat basal forebrain tissue were placed in culture at an age when neurogenesis in vivo is still active [embryonic day (E) 15]. The rapid mortality of these cells in defined medium, with 50% mortality after 5-10 h, was blocked completely by soluble proteins from the olfactory bulb (a basal forebrain target), extending earlier observations (Lambert, Megerian, Garden, and Klein, 1988). Treated cultures were capable of incorporating thymidine into DNA, and most cells incorporating 3H-thymidine (greater than 90%) also stained positive for neurofilament, confirming neuronal proliferation in the supplemented cultures. A small percentage of 3H-thymidine labelled cells were glial fibrillary acidic protein (GFAP) positive, but growth factors that support astroglial proliferation [epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and insulin-like growth factor (IGF-1)] were not sufficient for neuronal support. After 5 culture days with supplemented medium, almost 50% of the cells showed choline acetyltransferase (ChAT) immunofluorescence. The cholinergic neurons typically formed clusters separate from noncholinergic cells. These mature cultures did not develop if young cultures were treated with aphidicolin to block DNA synthesis. The data show that cultures of very young rat basal forebrain cells can be neurogenic, giving rise to abundant cholinergic neurons, and that early cell proliferation is essential for long-term culture survival. PMID- 1624934 TI - Structure of the caudal neural tube in an ascidian larva: vestiges of its possible evolutionary origin from a ciliated band. AB - Ultrastructural analysis and differential immunocytochemical staining with two antitubulin monoclonal antibodies were used to reexamine the organization and development of the neural tube in the larva of an ascidian, Ciona intestinalis, in appraisal of a theory that the dorsal tubular nervous system of the chordates evolved from two halves of a ciliated band in an auricularia-like larva of the kind found in echinoderms and hemichordates. One of the antibodies stained cilia in the nervous system and elsewhere; the other reacted primarily with neuronal axons. The caudal neural tube consists of four rows of large ciliated ependymal glial cells enclosing an axial neural canal into which their single cilia extend. Two ventrolateral nerve tracts, containing axons, arise in the posterior brain region and extend along the length of the caudal tube, partially surrounded by the ependymal cells. The nonnervous, ciliated, ependymal neural tube of the ascidian larva with its two associated nerve tracts survives as a primitive early condition that could result from a ciliated band transformation. Tissues in the distal-most part of the ascidian larval tail have cell lineage origins that indicate an evolutionary history different from those in the proximal majority of the tail. The ependymal cells in this presumed later addition to the tail are not ciliated, although all of the others in the caudal ependymal tube appear to be. PMID- 1624935 TI - Neurite outgrowth on a step gradient of chondroitin sulfate proteoglycan (CS-PG). AB - Sulfated proteoglycans (PGs) may play a significant role in the regulation of neurite outgrowth. They are present in axon-free regions of the developing nervous system and repel elongating neurites in a concentration-dependent manner in vitro. The addition of growth-promoting molecules, such as laminin, can modify the inhibitory effect of PGs on neurite outgrowth (Snow, Steindler, and Silver, 1990b). Substrata containing a high-PG/low-laminin ratio completely inhibit neurite outgrowth, while normal, unimpeded outgrowth is observed on low-PG/high laminin substrata. Therefore, different patterns of neurite outgrowth may result from regulation of the ratio of growth-promoting molecules to growth-inhibiting molecules. Using video microscopy, embryonic chicken dorsal root ganglia neurons (DRG), chicken retinal ganglia neurons (RGC), and rat forebrain neurons (FB) were analyzed as they extended processes from a substratum consisting of laminin alone onto a step gradient of increasing concentrations of chondroitin sulfate proteoglycan (CS-PG) bound to laminin. In contrast to neurite outgrowth inhibition that occurs at the border of a single stripe of high concentration of CS-PG (Snow et al., 1990b and this study), growth cones grew onto and up CS-PG presented in a step-wise graded distribution. Although the behavior of the different cell types was unique, a common behavior of each cell type was a decrease in the rate of neurite outgrowth with increasing CS-PG concentration. These data suggest that appropriate concentrations of growth-promoting molecules combined with growth-inhibiting molecules may regulate the direction and possibly the timing of neurite outgrowth in vivo. The different responses of different neuronal types suggest that the presence of sulfated PG may have varying effects on different aspects of neuronal development. PMID- 1624936 TI - Synthesis, spectroscopic, cytotoxic, and DNA binding studies of binuclear 2,2' bipyridine-platinum(II) and -palladium(II) complexes of meso-alpha,alpha' diaminoadipic and meso-alpha,alpha'-diaminosuberic acids. AB - Four new binuclear complexes of formula [M2(bipy)2(BAA)]Cl2 (where M is Pt(II) or Pd(II), bipy is 2,2'-bipyridine, and BAA is a dianion of meso-alpha-alpha' diaminoadipic acid (DAA) or meso-alpha,alpha'-diaminosuberic acid (DSA) have been synthesized. These complexes have been characterized by chemical analysis and ultraviolet-visible, infrared, and 1H NMR spectroscopy. The mode of binding of ligands in these complexes has been ascertained by infrared and detailed 1H NMR spectroscopy. These complexes are 1:2 electrolyte in conductivity water. They have also been tested against P388 lymphocytic leukemia cells and their target is DNA molecules. [Pt2(bipy)2(DSA)]Cl2, [Pd2(bipy)2(DSA)Cl2, and [Pd2(bipy)2(DAA)]Cl2 show I.D.50 values comparable or lower than cis diamminedichloroplatinum(II) and [Pt(bipy)(Ala)]Cl. In addition, binding studies of [Pt2(bipy)2(DSA)]Cl2 and [Pd2(bipy)2(DAA)]Cl2 to calf thymus DNA have been carried out and the mode of binding seems to be hydrogen bonding, as suggested earlier for analogous mononuclear amino acid-DNA complexes. PMID- 1624937 TI - Specific nickel(II)-transfer process between the native sequence peptide representing the nickel(II)-transport site of human serum albumin and L histidine. AB - The kinetics and mechanism for Ni(II)-transfer of the native sequence tripeptide, L-aspartyl-L-alanyl-L-histidine-N-methylamide (AAHNMA), representing the Ni(II) transport site of human serum albumin (HSA) and L-histidine (L-His) was studied in forward and reverse reactions in the pH range 6.5 to 9.0 at I = 0.2 and 25 degrees C. For the Ni(II)-transfer from Ni(II)-(L-His)2 to native sequence peptide, the rate-determining step is the formation of a mixed-ligand complex of NiH-1AB by deprotonation of peptide nitrogen from NiAB where A and B denote the anionic forms of AAHNMA and L-His, respectively. For the Ni(II)-transfer from Ni(II)-peptide to L-His, the rate-determining step is a bond breaking between Ni(II) and peptide nitrogen to form NiH-1A by protonation to a peptide nitrogen of NiH-2A. The equilibrium constants for the metal-transfer reaction of MH-2A + 2HB in equilibrium MB2 + A (A = Ni(II), Cu(II] were 10(3.29) and 10(0.78) for Ni(II) and Cu(II), respectively. NiB2 is 324 times as stable as CuB2. Furthermore, the ratio of Ni(II)/Cu(II) in the rate constants for the reaction of MB2 with A was found to be 2.8 x 10(-4). Thus, despite the similarities of Cu(II) and Ni(II) in the metal-binding sites of HSA and in reaction mechanism, Ni(II)-(L His)2 complex is so stable thermodynamically and kinetically, compared to the Cu(II)-(L-His)2 complex, that Ni(II) is hardly transferred from Ni(II)-(L-His)2 to native sequence peptide. These findings may support specificities in the Ni(II)-transfer, its organ distribution, and its excretion through urine in vivo. PMID- 1624938 TI - Transgenic medicinal plants: Agrobacterium-mediated foreign gene transfer and production of secondary metabolites. AB - Agrobacterium-Ti/Ri plasmids are natural gene vectors, by which a number of attempts have been made in genetic engineering of secondary metabolism in pharmaceutically important plants in the last few years. Opines are biosynthesized by transformed crown galls and hairy roots integrated with T-DNAs of Ti/Ri plasmids. These opines are classified into five families according to their structures and biogenesis. The production of opines is a natural example of genetic engineering of the biosynthetic machinery of plant cells for the benefit of the bacterial pathogen. One recent advance in transgenic technology of potential value to pharmacognosy is an application of transgenic organ cultures such as hairy roots and shooty teratomas to over-production and biotransformation of secondary metabolites. The hairy roots induced by Ri plasmid of Agrobacterium rhizogenes have been proved to be an efficient means of producing secondary metabolites that are normally biosynthesized in roots of differentiated plants. So far the specific metabolites produced by hairy root cultures and/or plants regenerated from hairy roots of 63 species have been analyzed and reported. As an alternative means of producing metabolites normally produced in leaves of plants, the shooty teratomas incited by the tumor-forming Ti plasmid or a shooty mutant of Agrobacterium tumefaciens have been used for the de novo biosynthesis and biotransformation of some specific secondary products. A second and more direct way to manipulate secondary pathways is performed by transferring and expressing specifically modified genes into medicinal plant cells with Agrobacterium vector systems. The genes encoding neomycin phosphotransferase and beta-glucuronidase have been used as model genes under the transcriptional control of appropriate promoters. Recently some specific genes that can eventually modify the fluxes of secondary metabolism have been integrated and expressed in medicinal plant cells. Future prospects are also discussed. PMID- 1624939 TI - Chemical investigation and anti-inflammatory activity of Vitex negundo seeds. AB - The CHCl3 extract of the defatted seeds of Vitex negundo exhibited anti inflammatory activity and yielded four triterpenoids: 3 beta-acetoxyolean-12-en 27-oic acid [1], 2 alpha, 3 alpha-dihydroxyoleana-5,12-dien-28-oic acid [2], 2 beta,3 alpha-diacetoxyoleana-5,12-dien-28-oic acid [3], and 2 alpha,3 beta diacetoxy-18-hydroxyoleana-5,12-dien-28-oic acid [5]. This is the first report of the isolation of compounds 2, 3, and 5 from a natural source. PMID- 1624940 TI - Four new antibacterial sesterterpenes from a marine sponge of the genus Luffariella. AB - The structures of four new sesterterpenoid compounds 1-4 isolated from a marine sponge of the genus Luffariella, collected from The Great Barrier Reef, Australia, have been determined by analysis of their 1H-nmr, 13C-nmr, ir, uv, and eims spectral data. The new metabolites 1-4 were found to co-occur with the compounds manoalide, secomanoalide, Z-neomanolaide [5], and E-neomanoalide. PMID- 1624941 TI - Anti-HIV and cytotoxic alkaloids from Buchenavia capitata. AB - The anti-HIV activity in the organic solvent extract of leaves of Buchenavia capitata was traced to a series of known flavonoid alkaloids, which represent a new chemotype for anti-HIV activity. The 13C-nmr assignments for this series of compounds have been revised. O-Demethylbuchenavianine [1] was the most active compound of the series but produced only moderate cytoprotective effects against HIV in cultured human lymphoblastoid (CEM-SS) cells. Compound 1 was cytotoxic also in the NCI human disease-oriented in vitro tumor screening panel and produced a pattern of modest differential cellular sensitivity. PMID- 1624942 TI - Isolation and identification of xochitloldione and isoxochitlolone from Cnidosculus urens. AB - Major components of MeOH extracts from the plant roots of Cnidosculus urens purified by cc and tlc and crystallization were lupeol acetate and the previously unreported compounds isoxochitlolone [1] and xochitloldione [2], which were identified through mass, ir, nmr, and uv spectroscopy and X-ray crystallography. In preliminary testing, isoxochitlolone has been found to be active against Escherichia coli and Staphylococcus aureus. PMID- 1624943 TI - Isolation, NMR studies, and biological activities of onopordopicrin from Centaurea sonchifolia. AB - A sesquiterpene lactone, onopordopicrin [1], has been isolated from Centaurea sonchifolia. Its structure was established by 2D nmr (1H-1H and 13C-1H correlations), and the conformation in CHCl3 was examined by nOe studies. Cytotoxic, antibacterial, and antifungal activities are reported. PMID- 1624944 TI - NMR assignments of territrems A, B, and C and the structure of MB2, the major metabolite of territrem B by rat liver microsomal fraction. AB - The 1H- and 13C-nmr assignments of territrems A, B, and C [1-3] were made by using nOe and 2D nmr techniques. Following the same methods, the structure of MB2 [4], the major product of territrem B incubated with rat liver microsomal fraction, was determined as a hydroxylation product at the pro S methyl group of C-4 of territrem B. PMID- 1624945 TI - Distribution of materials from the Natural Products Repository of the National Cancer Institute (NCI) PMID- 1624946 TI - Platelet activity and stroke severity. AB - Although platelets constitute the major component of a thrombus, its role in determining the clinical severity of thrombotic stroke is unknown. Therefore, we investigated the relationship between platelet ionized calcium ([Ca2+i]), a measure of platelet activity and presumably proneness to thrombosis, and clinical stroke severity in 45 consecutively studied acute ischemic stroke patients. Even though there was no correlation between the clinical neurological scores and the levels of baseline and activated platelet [Ca2+i], stroke was less severe in patients who had been taking aspirin at the time of stroke onset. These results raise several important questions: (a) is the extent of platelet activation a reflection of thrombus volume, (b) does the clinical severity of neurological deficit reflect the causative thrombus volume, and (c) whether the beneficial effect of aspirin in stroke prophylaxis is through its inhibition of platelets alone. PMID- 1624947 TI - Cholinergic markers in ALS spinal cord. AB - We analyzed binding sites for quinuclidinyl benzilate (QNB) and hemicholinium-3 (HC-3) by quantitative slice autoradiography and the activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in spinal cord of 5-7 patients with amyotrophic lateral sclerosis (ALS). In the ventral horn, QNB binding sites were markedly reduced (38% of controls; P less than 0.001), whereas HC-3 binding sites were only moderately affected (76%, P less than 0.01). Losses in cholinergic marker enzymes were inconsistent. The loss of muscarinic binding sites in the ventral horn was the most reliable cholinergic disease marker in ALS. PMID- 1624948 TI - Recovery functions of somatosensory evoked potentials in parkinsonian patients. AB - The aim of this study was to analyze the recovery functions of median nerve somatosensory evoked potentials (SEPs) and to clarify changes in the somatosensory system of patients with Parkinson's disease (PD). The central and frontal SEPs and the nerve potential of the median nerve were examined. The latencies and amplitudes of SEPs produced by a single shock in patients with PD were normal. The recovery functions of central SEPs showed a low degree of suppression in patients with PD, although the recovery curve of the nerve potential in PD patients was almost normal. The change in recovery curves of SEPs in patients with sensory complaints were more noticeable than that in patients without sensory disturbance. A low degree of suppression of central SEPs might play a role in the sensory complaints of PD patients. PMID- 1624949 TI - The association of astrocytoma and pituitary adenoma in a patient with alcaptonuria. AB - A female patient with a juvenile pilocytic astrocytoma and a pituitary adenoma is described. The patient also has alcaptonuria, a rare inborn error of metabolism with autosomal recessive mode of inheritance. The association of these three disorders has never been reported previously. The possible existence of a common genetic factor in the development of both tumors and alcaptonuria is discussed. PMID- 1624950 TI - 1-H-localized magnetic resonance spectroscopy: preliminary observations in transient ischemic attacks. AB - Water-suppressed proton magnetic resonance spectroscopy which has recently shown diagnostic potential in human stroke victims was performed in two patients who had suffered a hemispheric transient ischemic attack. Localized spectra were targeted from routine MR images. In one patient lactate could be observed 8 weeks after a transient ischemic attack. Lactate concentration was low compared with that of a patient who had suffered acute stroke. The other TIA patient did not show evidence of lactate production. Although these observations are preliminary, we demonstrated that localized in vivo proton spectroscopy can detect persistent biochemical alterations after transient ischemic attacks. We suggest that non invasive in vivo proton spectroscopy will become a useful method in diagnosis and management of TIA in the future. PMID- 1624951 TI - Pathology of the cerebellar dentate and interpositus nuclei in Joseph disease: a morphometric investigation. AB - Cerebellar dentate and interpositus nuclei pathology was studied morphometrically in 3 patients with Joseph disease compared to 3 control subjects. Size of neurons, number of small neurons (cell body area: 50-199 microns 2) and large neurons (cell body area: 200 microns 2 or greater) at the rostral, medial and caudal levels, neuronal cell density, total volume of the gray bands, and total neuronal cell number were evaluated in the dentate, emboliform, and globose nuclei, using an image analyzer, after making horizontal serial 20-microns thick sections of a unilateral cerebellar hemisphere embedded in celloidin. The number of large neurons in Joseph disease was around 20% of that in the controls at each level in the individual nucleus (P less than 0.05 or P less than 0.01). In contrast, the number of small neurons was significantly reduced only at the caudal level of the dentate nucleus (P less than 0.05). The neuronal cell density was decreased within the nuclei. The total volume of the gray bands was reduced to about 70% within the nuclei (P less than 0.05 or P less than 0.01). The total number of neurons was decreased to about a third, a half, and a third within the dentate (P less than 0.001), emboliform (P less than 0.01), and globose nuclei (P less than 0.001), respectively. The principal pathologic change of the dentate and interpositus nuclei in Joseph disease was severe loss of neurons, with significant loss of the large neurons, indicating that Joseph disease is a type of cerebellar efferent system disorder. PMID- 1624952 TI - Electronmicroscopic observation of amyloid deposits in the vascular walls of the choroid plexus in systemic amyloidosis. AB - This report concerns an ultrastructural study of the vessels of the choroid plexus in 3 cases of systemic amyloidosis, sections of formalin-fixed brains being used. Small-sized arteries and arterioles were mainly affected by deposition of amyloid fibrils. In the arterioles, the amyloid fibrils were often so densely accumulated that they separated individual smooth muscle cells of the media and reached the subendothelial region. The basal surface of the endothelium of such vessels showed frequent invaginations filled with amyloid tufts; some of the tufts displaced the thin cytoplasm of the endothelial cells toward the lumen. Occasionally, tufts of amyloid fibrils were found to be exposed to and to float in the vascular lumen. These observations were made only in severely amyloid laden vessels. Among the several possibilities regarding the tuft-endothelial relationship, the transendothelial transport of amyloid tufts is most likely, but the possibility of intraendothelial processing of amyloid precursor proteins and their secretion to form fibrils extracellularly cannot be excluded. PMID- 1624953 TI - Hyperthermic injury versus crush injury in the rat sciatic nerve: a comparative functional, histopathological and morphometrical study. AB - Functional and morphological changes of the rat sciatic nerve after local hyperthermia (30 min, 45 degrees C) and crush treatment were compared. After hyperthermic injury nerve function loss developed in a time period of about 7 h. Nerve crush led to an immediate loss of nerve function. Nerve function loss was assessed by a motor and a sensory function test. Recovery from function loss took place in both treatment groups and was complete in 4-5 weeks. Early (within 8 h post-treatment) histopathological changes in the nerve after heating included edema, possible blood stasis and changes in the blood vessel wall, like swelling of the media. During this period some axonal changes were observed. Immediate after crushing axons were severely damaged, while many blood vessels remained normal. Within one week after both treatments, degeneration of axons and myelin was observed at the site and distal from the site of the lesion (Wallerian degeneration). Three weeks after treatment a major part of the axons had regenerated and remyelinated. Vascular changes at the site of lesion could still be observed in the heat-treated nerves. Twelve weeks after both treatments, blood vessels appeared to be normal again. Morphometrical analysis of the treated nerves confirmed the histological observations. Three and 12 weeks after treatment average axon diameters were significant smaller and average myelin sheaths were significant thinner compared to untreated nerves. These parameters did not differ significantly when the two treatment groups were compared. PMID- 1624954 TI - Mechanisms of oligodendrocyte interaction with normal human serum--defining the role of complement. AB - The interaction of human serum with oligodendroglia was investigated in vitro using purified cultured neonatal rat oligodendrocytes. Previous evidence for antibody independent classical pathway complement activation was confirmed; the results also showed a deficit in the protection of rat oligodendrocytes from complement attack suggesting a deficiency in the expression of terminal regulatory proteins of the complement cascade. Thus, rat oligodendrocytes are selectively sensitive to normal serum due both to complement activation and impaired protection from terminal complement attack. PMID- 1624955 TI - Computational simulations of the conformational behaviour of the adhesive proteins RGDS fragment. AB - Many adhesive proteins present in extracellular matrices and in blood contain the tetrapeptide sequence -Arg-Gly-Asp-Ser- (or RGDS) at their cell recognition site. Since this sequence, or similar ones, was found in many proteins involved in major biological mechanisms, conformational investigations were performed on the RGDS fragment. A preliminary review of available crystal structures indicates that the RxDy sequences exhibit 3 well-defined structural patterns: one corresponding to a strong interaction between the Arg and Asp ionic side chains which are only about 4 A apart, one with the ions separated by about 8 A, and another in which the side chains are further apart (about 11 A). The conformational behaviour of the isolated RGDS fragment was next tackled using sequential building, Monte Carlo and molecular dynamics computational techniques. Analysis of the RGDS sequence conformational possibilities, as simulated in vacuum and in water solution, indicates that they can be classified into several conformational classes, which correspond roughly to the behaviour of the RGDS fragment as observed in protein matrices. This suggests the possibility of understanding the biological role of the RGDS or parent sequences in recognition processes. PMID- 1624957 TI - Characterization of low-energy conformational domains for Met-enkephalin. AB - An extensive exploration of the conformational hypersurface of Met-enkephalin has been carried out, in order to characterize different low-energy conformational domains accessible to this pentapeptide. The search strategy used consisted of two steps. First, systematic nested rotations were performed using the ECEPP potential. Ninety-two low-energy structures were found and minimized using the CHARMm potential. High and low-temperature molecular dynamics trajectories were then computed for the lowest energy structures in an interative fashion until no lower energy conformers could be found. The same search strategy was used in these studies simulating three different environments, a distance-dependent dielectric epsilon = r, and two constant dielectrics epsilon = 10 and epsilon = 80. The lowest energy structure found in a distance-dependent dielectric is a Gly Gly beta-II'-type turn. All other structures found for epsilon = r within 10 kcal/mol of this lowest energy structure are also bends. In the more polar environments, the density of conformational states is significantly larger compared to the apolar media. Moreover, fewer hydrogen bonds are formed in the more polar environments, which increases the flexibility of the peptide and results in less structured conformers. Comparisons are made with previous calculations and experimental results. PMID- 1624956 TI - In search of new lead compounds for trypanosomiasis drug design: a protein structure-based linked-fragment approach. AB - A modular method for pursuing structure-based inhibitor design in the framework of a design cycle is presented. The approach entails four stages: (1) a design pathway is defined in the three-dimensional structure of a target protein; (2) this pathway is divided into subregions; (3) complementary building blocks, also called fragments, are designed in each subregion; complementarity is defined in terms of shape, hydrophobicity, hydrogen bond properties and electrostatics; and (4) fragments from different subregions are linked into potential lead compounds. Stages (3) and (4) are qualitatively guided by force-field calculations. In addition, the designed fragments serve as entries for retrieving existing compounds from chemical databases. This linked-fragment approach has been applied in the design of potentially selective inhibitors of triosephosphate isomerase from Trypanosoma brucei, the causative agent of sleeping sickness. PMID- 1624958 TI - Structure-activity relationships of pyrethroid insecticides. Part 2. The use of molecular dynamics for conformation searching and average parameter calculation. AB - Molecular dynamics simulations have been performed on a number of conformationally flexible pyrethroid insecticides. The results indicate that molecular dynamics is a suitable tool for conformational searching of small molecules given suitable simulation parameters. The structures derived from the simulations are compared with the static conformation used in a previous study. Various physicochemical parameters have been calculated for a set of conformations selected from the simulations using multivariate analysis. The averaged values of the parameters over the selected set (and the factors derived from them) are compared with the single conformation values used in the previous study. PMID- 1624959 TI - When is an answer the answer? PMID- 1624960 TI - Conformational search by potential energy annealing: algorithm and application to cyclosporin A. AB - A major problem in modelling (biological) macromolecules is the search for low energy conformations. The complexity of a conformational search problem increases exponentially with the number of degrees of freedom which means that a systematic search can only be performed for very small structures. Here we introduce a new method (PEACS) which has a far better performance than conventional search methods. To show the advantages of PEACS we applied it to the refinement of Cyclosporin A and compared the results with normal molecular dynamics (MD) refinement. The structures obtained with PEACS were lower in energy and agreed with the NMR parameters much better than those obtained with MD. From the results it is further clear that PEACS samples a much larger part of the available conformational space than MD does. PMID- 1624961 TI - Dubious evidence of heart and cancer deaths due to passive smoking. PMID- 1624962 TI - Passive smoking causes heart disease and lung cancer. PMID- 1624963 TI - Sleep apnea syndrome symptoms and automobile driving in a general population. AB - Automobile accidents are reported as being overrepresented in those suffering from the obstructive sleep apnea syndrome (SAS), evident by snoring, sleep disturbances and diurnal hypersomnia. An estimation of the prevalence of these symptoms amongst an adult population, predominantly automobile drivers, was assessed by using a one-stage questionnaire procedure. From a national random sample of 1214 persons a weighted reply rate of 76% was achieved. Snoring, breath cessations, mid-sleep awakenings, and diurnal hypersomnia were reported in 24, 3.8, 27 and 9.1%, respectively. The maximum prevalence of SAS was estimated as 2.8-5.5% among men, aged 30-69 years, depending on definition used. Driving frequency in potential sleep apneics was similar to that of the entire population studied. Diurnal hypersomnia, considered a consequence of SAS, was reported as an overall 2.2%, corresponding to 100,000 automobile drivers in Sweden. PMID- 1624964 TI - The differential diagnosis of primary lung cancer: inter-observer agreement and contribution of specific diagnostic procedures. AB - In order to investigate inter-observer variability in the differential diagnosis of primary lung cancer among women and the contribution of specific diagnostic procedures to this diagnosis, a group of 449 suspect cases of this disease was studied. Based on a standard dossier (including clinical data and the reports, if present, of radiology, bronchoscopy and histology) six different physicians independently judged, for each woman, at each diagnostic step, the presence of a primary lung cancer. A final consensus was organized in order to define the true cases. Radiology and especially histology seem to give the most important contribution to the diagnosis. On the other hand bronchoscopy seems to be useful mainly as a guide for biopsy. A predictive value of 90% was found when both radiology and bronchoscopy were positive; in the other cases histology seems to be needed to reach an adequate discrimination. Inter-rater agreement increases with an increasing amount of information but is not very high even when histology is available. PMID- 1624965 TI - Epidemiology of diabetes mellitus in southern Italy: a case-finding method based on drug prescriptions. AB - The study evaluates whether data concerning drug prescriptions available from the National Health System (NHS) can be used to provide an estimate of the prevalence and pattern of treatment of diabetes in a well defined health district in southern Italy. In Italy virtually all drug prescriptions are obtained through the NHS. For a period of three consecutive months all prescriptions of insulin, hypoglycemic agents and strips for blood and urine testing were monitored in a well defined area near Naples. 2958 cases were thus identified giving a prevalence of drug treated diabetes mellitus of 2.01%; prevalence was higher in females than in males (2.68 vs 1.35%) and increased with age from 0.05% in the age group below 9 years to 13.67 in the age group over 70 years. This case finding procedure was validated by cross-check with independent sources of cases. To evaluate the sensitivity of the method a list of 820 "known" cases of drug treated diabetes mellitus was obtained from a random sample of local general practitioners (GPs) and diabetic clinics: 73.5% of these cases were also detected through the analysis of drug prescriptions. To evaluate the probability of misclassification a random subsample of 602 cases identified through prescriptions was submitted to the GPs working in the study area, for 517 the diagnosis of diabetes was confirmed, thus yielding a positive predictive value of 85.9%. After correction for sensitivity and probability of misclassification the prevalence of drug treated diabetes in our population was 2.52%. The pattern of prescriptions in this population is also given.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1624966 TI - Risk factors for cardiovascular disease in the developing world. A multicentre collaborative study in the International Clinical Epidemiology Network (INCLEN). INCLEN Multicentre Collaborative Group. AB - Twelve centres in 7 countries in the Developing World (China, Thailand, the Philippines, Indonesia, Chile, Colombia and Brazil) connected with the International Clinical Epidemiology Network (INCLEN) each measured cardiovascular disease (CVD) risk factors in random samples of approx. 200 men aged between 35 and 65 years. Samples of men aimed to be representative of the population from which they were drawn, but the population in each centre was not designed to be representative of the whole country. Cigarette smoking rates varied from 16 to 78% and mean cholesterol levels varied from 3.8 to 6.4 mmol/l. In Bogota, Colombia, 46% of the men had a cholesterol level greater than 6.5 mmol/l and in another 5 communities 19% or more of the population had these levels. A body mass index (BMI) of greater than 25 was seen in more than 50% of 4 communities and a blood pressure greater than or equal to 160 mmHg systolic and/or 95 mmHg diastolic was found in more than 20% of 6 countries. BMI was strongly correlated with blood cholesterol and blood pressure levels in almost all population groups. It would appear that many communities in the Developing World have high levels of risk factors for CVD and that steps could well start to be taken now to prevent the emergence of CVD epidemics in the future. PMID- 1624967 TI - A coronary primary prevention study of Scottish men aged 45-64 years: trial design. The West of Scotland Coronary Prevention Study Group. AB - This paper describes the design of the West of Scotland Coronary Prevention Study (WOSCOPS) which is a primary prevention trial involving men aged 45-64 yr with raised plasma cholesterol levels. The principal aim is to test the hypothesis that reduction of serum cholesterol by treatment with pravastatin [a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase--a regulatory enzyme in cholesterol synthesis] over an average period of 5 yr will lead to a reduction in fatal and non-fatal myocardial infarction. A trial population of approx. 6500 men have been randomized in equal numbers to treatment with placebo or pravastatin. At the time of randomization, these men have no evidence of previous myocardial infarction. All subjects are given smoking and dietary advice throughout the study. The principal endpoints are: (i) coronary heart disease death plus non-fatal myocardial infarction, (ii) coronary heart disease death, and (iii) non-fatal myocardial infarction. PMID- 1624968 TI - Health and social consequences for relatives of demented and non-demented elderly. A population-based study. AB - A population-based study was performed to investigate the subjective and objective burden due to caring for a demented relative. All the relatives of the subjects with cognitive impairment, detected in a district of Stockholm, living at home, were included in the study. When compared with relatives of elderly, mentally healthy persons living at home in the same district, they had high ORs for subjective burden and for use of psychotropic drugs. Spouses were the most stressed. However, the ORs for use of medical facilities and somatic drugs were close to unity, showing that caring for a demented person did not affect the physical health of the relative. A second comparison between relatives of demented persons living at home and in institutions, showed that the relatives of institutionalized subjects were less frequently spouses and had more problems with their physical health, but both groups had similar subjective feeling of stress. PMID- 1624969 TI - Acute rheumatic fever and the evolution of rheumatic heart disease: a prospective 12 year follow-up report. AB - Sixty four children who presented with the initial attack of acute rheumatic fever and maintained continuous regular secondary prophylaxis, were followed up prospectively for 12.3 years (an observation period of 775 patient-years). The prevalence rate of rheumatic heart disease in the 29 children who had carditis in the initial attack and in the 35 children who had no carditis initially was 49 vs 0%, respectively. The overall prevalence rate of rheumatic heart disease was 20%. Mitral incompetence developed in 11 patients (17%), aortic incompetence in 2 (3%) and mitral stenosis in 2 (3%). None of the patients developed aortic stenosis. Two recurrences developed with a recurrence rate of 0.003 per patient per year. One patient needed cardiac surgery and there was no mortality. These data strongly suggest that continuous regular secondary prophylaxis can prevent or significantly reduce the development of mitral and aortic valve stenosis, the prevalence rate of rheumatic heart disease and mortality. PMID- 1624970 TI - Comparison of two physical activity questionnaires, with a diary, for assessing physical activity in an elderly population. AB - Measurement of physical activity in epidemiological studies is usually achieved by means of a questionnaire. Little work has been done to determine which questionnaire format has greater validity in an elderly population. In this study of elderly subjects, physical activity as reported in two self-administered questionnaires (A and B), which differed in format and length, were compared to activity reported in a 4 day diary. As compared with the diary, moderate/heavy activity was more accurately reported in Questionnaire A (mean difference 5 min), the longer more detailed questionnaire, than B (mean difference 170 min). Light activity was under reported in Questionnaire A (mean difference 68 min) and over reported in B (mean difference 88 min) as compared with the diary. In contrast, time spent sitting was more accurately reported in Questionnaire B (mean difference 40 min) than in A (mean difference 230 min) as compared with the diary. The longer more detailed questionnaire was the more accurate instrument for assessing moderate/heavy activity in this elderly population. The shorter questionnaire was more accurate for assessing time spent sitting. PMID- 1624971 TI - Bias in meta-analytic research. AB - With the proliferation of meta-analyses in the medical literature have come conflicting studies. In addition, observance of guidelines for the performance of meta-analyses has been spotty. Bias may explain conflicting studies and differentiate carefully performed meta-analyses from others. Meta-analysts may fail to anticipate biases which threaten their study's validity. The three stages at which bias can be injected into a meta-analysis are finding studies, selection of the identified studies for the meta-analysis and extraction of data from the selected studies. This manuscript reviews specific types of bias which are common at each of these stages. PMID- 1624972 TI - Laboratory profile of sickle cell disease: a cross-sectional analysis. The Cooperative Study of Sickle Cell Disease. AB - We have collected steady-state laboratory data for over 2600 patients, age 2 years and over, with sickle cell anemia (HbSS), HbSC disease, and HbS-beta(+) thalassemia. The packed cell volume (PCV) is lower in males than in females until 17 or 18 years of age in HbSS and ages 13 to 15 in HbSC, but then becomes consistently higher in males. After age 40, the PCV falls in HbSS. The steady state leukocyte count in HbSS is higher than that in normals, blunting the utility of this measurement in the assessment of infection. In HbSC and HbS beta(+)-thalassemia, the leukocyte counts are more often within the range of normal. Platelet counts in HbSS are often found to be above normal and show a downward trend with age. There is a progressive rise in creatinine with age. In HbSS, this rise begins at age 14 and may be accounted for by the increased muscle mass that occurs with puberty. The further deterioration of renal function in patients over 20 may be a result of the known adverse effects of sickle cell disease upon the kidney. Our data provide a basis to compare perturbations caused by intercurrent complications and new therapies, as well as to contrast with similar information from other populations of patients with sickle cell disease. PMID- 1624973 TI - Soft drink consumption and urinary stone recurrence: a randomized prevention trial. AB - The object of this study was to determine if a strong association between soft drink (soda) consumption and recurrence of urinary stone disease, found in an earlier case-control study of adult males, had a causal component. The study sample consisted of 1009 male subjects, who completed an episode of urinary stone disease, who were aged 18-75 at that time, and who reported consuming at least 160 ml per day of soft drinks. Half of the subjects were randomized to refrain from consuming soft drinks, while the remaining subjects served as controls. The intervention group had an observed 6.4% advantage in actuarial 3 yr freedom from recurrence (p = 0.023 one-sided) over the control group. One important secondary finding was that for those who reported at the time of the index stone that their most consumed drink was acidified by phosphoric acid but not citric acid, the experimental group had a 15% higher 3 yr recurrence-free rate than the controls, p = 0.002, while for those who reported at the time of the index stone that their most consumed drink was acidified by citric acid with or without phosphoric acid, the experimental group had a similar 3 yr recurrence-free rate to the controls, p = 0.55. This interaction was significant, p = 0.019. PMID- 1624974 TI - Prevalence of isthmic lumbar spondylolisthesis in middle-aged subjects from eastern and western Finland. AB - Isthmic spondylolisthesis of the lumbosacral spine is a common radiologic finding in patients with low back pain, but its prevalence in unselected populations is poorly known. We examined X-ray pictures of the lumbosacral region of 1147 randomly selected 45-64-yr-old subjects living in eastern or western Finland. Of them, 69 subjects were found to have isthmic spondylolisthesis. The finding was more common in men (7.7%) than in women (4.6%; p = 0.026). The prevalence of spondylolisthesis was not age-related; it was higher in women with an occupation causing a high back load than in those with a low load occupation (p = 0.049), but this difference was not seen in men. The prevalence of spondylolisthesis tended to be higher in women with multiple pregnancies than in those with less than or equal to 2 pregnancies (p = 0.074). Women from eastern Finland had a higher prevalence of spondylolisthesis (7.2%) than those from western Finland (2.6%; p = 0.007), whereas no such difference was seen in men. The difference in women may partly be explained by factors causing loading of the low back, i.e. heavier work and a higher number of pregnancies. PMID- 1624975 TI - Colon cancer and ulcerative colitis: an epidemiologic exercise revisited. PMID- 1624976 TI - "Prudence" and "evidence" in disease prevention. PMID- 1624977 TI - Community health nursing visits for at-risk women and infants. AB - The purpose of this study was to utilize the Barnard Model of parent-infant interaction and instruments from the Barnard Newborn Nursing Models study to assess 30 pregnancy clients and to help determine appropriate interventions. Upon consent, the 30 study participants were randomly assigned to one of three groups: primiparous, unmarried, or otherwise socially at-risk. Thirty-three percent of the participants were under 19 years of age. A doctorally prepared community health nurse (CHN) completed all interventions, including a comprehensive assessment. Over 20% of participants admitted mild to moderate abuse of alcohol, cigarettes, and/or street drugs during early pregnancy. Counseling/supportive interventions established rapport and encouraged women to develop and maintain healthy life-styles. The control group of 10 were evaluated when their infant reached 6 months. A second group was followed during pregnancy, then evaluated at 6 months. A third group of 10 women were followed through pregnancy and the first 6 months of their babies' lives. Results indicated that substance abuse stopped or substantially decreased during intervention. Mothers in the intervention groups had fewer perinatal complications and better parent-infant interaction scores than the controls. This research supports previous reports that home visitor programs foster more healthy pregnancies and improve child developmental outcomes. PMID- 1624978 TI - Living arrangements, visit patterns, and health problems in a nurse-managed clinic for the homeless. AB - The purpose of this article is to describe living arrangements, clinic visit patterns, and health problems of clients by age and gender in a nurse-managed clinic serving the homeless. The conceptual framework for this project was derived from a nursing perspective of community health. The problem classification scheme used included four domains of community health practice: environmental, psychosocial, physiological, and health-related behavior. Data were collected during each visit to a nurse-managed health clinic for the homeless for 18 months. The findings indicate that living arrangements and visit patterns vary by age and gender. Health problems associated with integument and income were identified as primary and secondary problems across all age groups. Six other health problems were shared across all age and gender groups as either primary or secondary: circulation, respiration, pain, nutrition, communication, and prescription medication. Substance misuse was not a primary problem noted by clients, but was commonly a secondary problem. Genitourinary problems were noted primarily to be problems of younger women. Implications for planning nursing services for the homeless are discussed. PMID- 1624979 TI - Mandatory HIV testing rejected. PMID- 1624980 TI - Expertise in community health nursing. AB - This article reports on a study of expertise in community health nursing. The objective of the study was to develop a model of expertise derived from identification of the characteristics and factors influencing clinical expertise in community health nurses (CHNs) practicing in district nursing, school health, and child health. Participant observations, individual interviews, and written retrospective accounts of clinical episodes were analyzed from 37 nurses (10 novices within the first year of community practice and 27 experts identified by peers and colleagues). The data identified the expert as someone in whom the following characteristics operate synchronously: knowledge; empathy; appropriate communication; holistic understanding; an ability to get right to the problem at hand; and self-confidence in her or his perceptions, judgments, and intervention strategies. The findings suggest that there is a combination of factors which influences the development of expertise. These include educational factors, personal factors, and experience. These factors are incorporated into the model of expertise. The data also suggest that, in order to educate for expert levels of practice, the educational process must be designed to stimulate the learner's perceptual as well as analytic abilities. This can best be achieved through clinical practice opportunities and through demonstrations and case studies which stimulate inferential and intuitive thinking in students. PMID- 1624981 TI - Health perceptions and behaviors of school-age boys and girls. AB - This study described and compared the health perceptions and behaviors of 83 school-age boys and girls. An age-appropriate interview schedule was designed to collect data related to demographic characteristics, health perceptions, safety, life-style practices, nutrition, dental health, and care of minor injuries. Findings indicated that most boys and girls viewed themselves as healthy and managed their own care fairly well in the areas of seat belt use, exercise, and dental health. Nutrition was identified as an area of concern, with 10% of the children skipping breakfast, and over half eating snacks with empty calories. Generally, children were found to be knowledgeable in the management of simple injuries and how to respond in the event of an emergency. Boys and girls were similar in all areas of health perceptions and behaviors except for dental health, with boys reporting more regular visits to the dentist than did girls. Further research is needed to learn more about the process by which school-age children acquire positive health behaviors to assist nurses to design and implement intervention programs that appropriately address the needs of this age group. PMID- 1624982 TI - Injection sites utilized for DPT immunizations in infants. AB - The purpose of this investigation was to determine the site utilized by nurses for administering Diphtheria and Tetanus Toxoids and Pertussis (DPT) injections to infants under 7 months of age. Twenty-six of the 28 agencies identified in a metropolitan area as administering DPT injections chose to participate in the study. Those individuals administering DPT injections in the agencies completed a questionnaire with a return rate of 69% (n = 55). Forty-four participants indicated that they used the anterolateral thigh, the recommended site, 100% of the time. The participants in the study administered a total of 1,453 DPT injections per month. Eighty-seven percent of those injections were administered in the anterolateral thigh, 3.6% were given in the deltoid, 5.1% were given in the dorsal gluteal, and 4% were given in the ventrogluteal. The estimated proportion of DPT injections administered at the correct site was 84.65% which is much lower than the critical value 94.06% for alpha = .05 (p less than .00001). PMID- 1624983 TI - Enuresis: nursing diagnoses and treatment. AB - Living with a child with enuresis is not a major or critical problem, but it is a difficult and frustrating one. Wet sheets, wet pajamas, and rooms that smell of urine all add to the dismay felt by child and parents. Enuresis is a common problem which affects 22% of 5 year olds and 10% of 10 year olds (Scipien, Barnhart, Chard, Howe, & Phillips, 1986). Boys are affected more often than girls. There tends to be few answers given in the health-care system for the problem other than, "he'll out-grow it." Community health nurses (CHNs), working in the clinic, in the school setting, or in the home, may find parents and sometimes the child asking for help with this problem. This article presents the most common nursing diagnoses that apply to the family of an enuretic, and nursing interventions that can guide the nurse in working with the family to secure successful methods of treatment. PMID- 1624984 TI - Acute MI: a review of pathophysiology, treatment, and complications. AB - Few areas of clinical medicine have undergone advancements in the last decade as dramatic as those in the management of acute myocardial infarction (AMI). Nursing care of the AMI patient should be based on a comprehensive knowledge of the pathophysiology involved in order to intervene appropriately, understand medical therapies utilized, and anticipate complications. This article offers an in-depth review and update of the pathophysiology of AMI, current recommendations regarding management of the patient with acute infarction, and an overview of complications that still pose a threat to recovery in some patients. PMID- 1624985 TI - Mitral regurgitation as a complication of MI: pathophysiology and nursing implications. AB - Mitral regurgitation as a complication of myocardial infarction may be caused by papillary muscle dysfunction, papillary muscle rupture, or rupture of the chordae tendineae. Prompt diagnosis and intervention are necessary to reduce associated mortality and morbidity. The cardiovascular nurse is integrally involved in all phases of treatment for this condition. The pathophysiology, clinical course, and current treatment modalities utilized for postinfarction mitral regurgitation are described, enabling the cardiovascular nurse to develop a comprehensive plan of care. PMID- 1624986 TI - Ventricular septal and free wall rupture complicating acute MI. AB - This article discusses rupture of the free wall of the left ventricle and ventricular septal defect (VSD). Although both entities occur infrequently, they remain prominent causes of death from acute myocardial infarction (AMI). Rupture of the free wall varies from an acute tear to a slow, incomplete, or subacute rupture. A VSD resulting from an AMI may be simple or complex. A simple rupture is a direct opening in the ventricular system. A complex rupture ascribes an undulating course. Although VSD is potentially amendable to surgical therapy, free wall rupture is usually immediately fatal. Because rapid identification with aggressive treatment potentially influences patient outcome, cardiovascular nurses need to be able to rapidly identify patients experiencing these cardiac rupture syndromes. Nurses provide the important physiologic and psychosocial support that is necessary for patient survival and successful adaptation. PMID- 1624987 TI - Acute post-MI pericarditis. AB - The diagnosis of acute pericarditis may be difficult to establish in patients with recent transmural infarcts as the symptomatology frequently mimics the clinical presentation associated with recurrent ischemia. A careful assessment of the postmyocardial infarction patient may reveal the clinical and electrocardiographic features associated with developing pericarditis. Prompt and accurate recognition of this complication is critical in order to institute definitive therapy, minimize the risk of hemodynamic compromise, and provide psychological support. PMID- 1624988 TI - Psychosocial adjustment following MI: current views and nursing implications. AB - Psychosocial adjustment following myocardial infarction (MI) has received significant research attention during the past 20 years. This article highlights research addressing the relationship of anxiety, depression, and denial in influencing specific outcomes following MI. Additional research describing patterns of emotional response to MI is also included. Based on reported research, specific nursing interventions, in a care plan format, are suggested to foster positive psychosocial outcomes in the post-MI patient. Even though a significant amount of research has been completed on this subject, definitive conclusions regarding patient management supportive of positive outcomes are not possible. Suggestions for future research focus on this topic area are identified. PMID- 1624989 TI - Reduced cardiac output and exercise capacity in patients after MI. AB - This article summarizes the literature and suggests directions for future research concerning rehabilitation potential, impairment, and reduced cardiac output after myocardial infarction (MI). Current evidence suggests that cardiac output and maximal exercise capacity are reduced in some post-MI patients. The conceptual model of rehabilitation potential presented emphasizes the need for careful assessment of the state of underlying pathology present after MI when evaluating the response to exercise or exercise training. PMID- 1624990 TI - Computerized myocardial ischemia detection. AB - With early detection and timely intervention, the effects of ischemia are reversible. Without intervention, ischemia causes myocardial injury, which is usually evidenced by ST elevation. Computerized ST segment analysis performed by the bedside monitor can assist clinicians in the early recognition of ischemia, allowing prompt intervention and timely evaluation of treatment effectiveness. PMID- 1624991 TI - Depression in the post-MI patient. AB - Current nursing research has focused on the psychosocial complications and adjustment following myocardial infarction (MI). Depression can impair optimal recovery by the patient and family after MI. This article reviews and critiques two nursing studies related to depression. The first study focuses on reliably assessing depression in the post-MI patient. The second study explores the psychophysiologic link between depression and hypoxia. Implications for practice and further research are discussed. PMID- 1624992 TI - Task analysis of the ODU 11/12 explorer. PMID- 1624993 TI - Reasons for changing employment positions among practicing North Carolina dental hygienists. AB - This study sought to identify factors associated with dental hygienists' decisions to leave one dental office and commence practice in another. Although dental hygienists' decisions to leave the profession have been examined in some detail, this more common phenomenon of changing positions has not been carefully examined. All currently practicing dental hygienists in North Carolina were surveyed in 1990, as a part of a cooperative project addressing retention of dental office team members. The survey collected information concerning the 976 respondents' (51% response rate) employment experience, reasons associated with leaving past positions, current job and career satisfaction, and personal characteristics. These data were analyzed to determine factors associated with both reported position changes and respondents' predictions of their professional activity status five years hence. No one reason or group of related reasons predominated among respondents' indicated reasons for leaving past positions. Approximately 25% of all changes were related to family responsibilities or spouse relocation. A larger proportion of changes was associated with a variety of job-related factors. Length of time in current position was not strongly related to job or career satisfaction, or to specific employment arrangements. The satisfaction measures were strongly associated with respondents' predictions of future activity status, while the employment arrangements were not. The results indicate that position changes occur for a variety of reasons, most, but not all, of which represent problems amenable to resolution through interventions designed to improve aspects of management within the practice. PMID- 1624994 TI - Dental hygiene students' and practitioners' resolution of professional issues. AB - The purpose of this study was to investigate the relationship among verbal ability, extent of education and professional experience, level of cognitive development, and age (separately and in combination) and dental hygiene students' and practitioners' ability to resolve professional issues. Forty-five dental hygiene students and graduates participated in this cross-sectional study (15 associate-degree subjects with no professional experience; 15 associate-degree subjects with professional experience; and 15 baccalaureate-degree subjects with professional experience). Ability to resolve professional issues was measured using two professional issues cases developed by the investigator. Protocols were rated separately and blindly by two raters, resulting in high interrater reliability (r = .69) and agreement estimates (80%). Results revealed that subjects with higher levels of education and professional experience achieved higher scores on the professional issues cases. Multiple regression and part correlation analyses revealed that the independent variables, in combination and separately, were of questionable value in predicting ability to respond to professional issues. While no single variable was overwhelmingly predictive, the combination variable extent of education and professional experience appeared to be the best predictor. PMID- 1624995 TI - A national survey of outcomes assessment in dental hygiene programs. AB - The purpose of the study was to document methods of educational outcomes assessment currently utilized in U.S. dental hygiene programs. A survey was mailed in 1989 to 197 dental hygiene program directors. A closed- and open-ended questionnaire requested information on the extent of assessment and kinds of assessment measures in use. Responses were received from 152 directors (77%); frequency and percentage data were reported. Findings reveal that program directors are most often responsible for data collection and analysis. Assessment data are utilized most frequently for program improvement and future program planning; a majority of programs have already made changes due to outcomes assessment. A majority of directors perceive that their assessment measures demonstrate achievement of program goals and objectives. Programs are moving beyond use of licensure tests to assess educational outcomes. Assessment of knowledge and skills is commonly performed, assessment of values/beliefs is performed less frequently, and postgraduate surveys are generally used in the assessment of relationships/behaviors. PMID- 1624996 TI - A short-term epidemiological study of median nerve dysfunction in practicing dental hygienists. AB - The purpose of this study was to assess over time changes in median nerve function in a group of 20 students who entered the University of Minnesota dental hygiene program in 1986. This is a follow-up report on 16 of the 20 students who were evaluated two years postgraduation in 1990. Comparisons were made with prior evaluations of the subjects completed at graduation in 1988, and one year postgraduation in 1989. Digital vibrometry was used to evaluate median nerve sensibility threshold at each of the time periods studied. Analysis revealed that after one year of clinical practice, there was a mean sensibility threshold shift of 11.04% in the left median nerve and 8.42% in the right median nerve as measured by digital vibrometry. Results at two years postgraduation indicated that the threshold shift observed in an earlier study had been arrested. The reasons appeared to be twofold: (1) a period of work hardening with a concept of neuromuscular ligamentous tissue hypertrophy or adaptation to the rigors of dental hygiene practice, and/or (2) the practicing dental hygienist had learned to become more efficient in the provision of hygiene procedures. There were no reported symptoms of median nerve dysfunction and none of the subjects had been diagnosed as having CTS at any time during the two years since graduation. Continued evaluations will be necessary to determine whether the observations noted during the second year postgraduation evaluation indicated temporary or permanent slowing of the conditions necessary for the development of CTS. PMID- 1624997 TI - Factors influencing the selection of dental hygiene as a profession. AB - Since the mid-1970s, the dental hygiene profession has experienced a decline in the number of applicants. Reasons cited for this decline are fewer traditional college-age students, an increase in the career opportunities available to women, and a decrease in student financial aid. Four-year dental hygiene programs have experienced applicant decline faster than two-year programs. The purpose of this study was to determine factors that influenced university freshmen to designate dental hygiene as a career choice. Factors examined included reasons for choosing or not choosing a career in dental hygiene, and retention in the college major chosen. A questionnaire was mailed to three groups of students who entered the University of North Carolina-Chapel Hill as freshmen from 1985 through 1987: (1) all students who designated dental hygiene as a major on their entrance application; (2) a random sample who did not; and (3) all the freshman during that time period who subsequently matriculated into the dental hygiene program. The overall response rate was 78% (n = 80). Subjects began to explore career opportunities at a mean age of 16. Having a family member/friend in the selected field was found to be the most influential factor in career selection. Among dental hygiene students, contact with a dental hygienist was perceived to be influential in their career choice. Entering college freshmen exhibited a lack of knowledge about the dental hygiene profession, and most had not received any information about dental hygiene in high school. These findings can be used to develop recruitment strategies. PMID- 1624998 TI - Carpal tunnel syndrome. Risk factors and preventive strategies for the dental hygienist. AB - Carpal tunnel syndrome (CTS) is well recognized as an occupational risk for dental hygienists. The contributing risk factors fall primarily into two categories: medical and occupational. The purposes of this paper are to examine the factors that predispose one to CTS in order to increase awareness among dental hygienists, and to offer preventive strategies that can be incorporated into daily practice. PMID- 1625000 TI - Use, need and desire for pain control procedures by Iowa hygienists. AB - A survey of dental hygienists licensed and residing in Iowa was conducted in the fall of 1987. The response rate after two mailings was 596 of 705 (84.5%). Of the 596, the responses of those who provided clinical services for adults in Iowa (n = 421) were analyzed for information regarding pain control. The survey was designed to collect demographic information and to determine hygienists' use and perception of the need and desire for pain control measures. Nearly 70% of the practitioners reported that their patients needed anesthesia but did not receive it. The main reason given for not asking their dentist/employer to provide pain control measures was that time did not permit. The estimated numbers of patients who received pain control measures per month was low: a mode of 1 with a median of 1 to 2 for local anesthesia, and a mode of 0 and median of 2 for nitrous oxide analgesia. Investigators examined the strength of correlations between the independent variables of practice and hygienist characteristics, and the dependent variables of use and perception of the need and desire for pain control measures. Hygienists who provided selected periodontal services and those who worked in periodontal practices were more likely to ask the dentist to provide pain control measures. Local anesthesia was used more frequently by those hygienists who saw more patients with pockets equal to or greater than 4 mm. Use of nitrous oxide analgesia in practice was highly correlated with preparation in the use of nitrous.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1624999 TI - Effectiveness of a continuing education course in local anesthesia for dental hygienists. AB - The knowledge, skill level, and clinical practice habits of 97 dental hygienists were assessed after the hygienists completed a 24-hour continuing education course in local anesthesia. Three survey methods were used to assess changes: a written pretest/posttest, self-reports, and employer-reported behavior change. The self-report was completed prior to the course and again one month and six months after completion of the course. The dentists/employers completed the survey after six months. Data were analyzed by paired t-tests. There was a significant improvement in knowledge between the pretest and posttest, an increase in the number of dental hygienists administering local anesthesia, and an increased frequency of its use in the practice setting at both one and six months after the course. The majority of the dentists/employers stated that completion of the course by the dental hygienists had a positive impact on their practices as demonstrated by the practice running more smoothly, improved quality of dental hygiene services, more satisfied patients, and increased productivity of the dental hygienists. PMID- 1625001 TI - Sexual harassment within dental offices in Washington State. AB - Sexual harassment has been identified as a significant problem for women in the work force today. The purpose of this pilot study was to provide a preliminary assessment of the perceived problem of sexual harassment of registered dental hygienists (RDHs) in Washington State. The specific aim of the fall 1990 study was to examine the following variables: incidence of sexual harassment in the dental workplace; frequency and severity; perpetrators; perceptions of the general seriousness of harassment in the oral healthcare professions; different actions taken by victims following harassment; known incidents in the workplace; and demographic characteristics of respondents, including career age, educational level, type of oral healthcare practice setting, and birth year. Data were gathered from a 30% random sample of 2,138 registered dental hygienists in Washington State (n = 650) by means of a questionnaire. An initial mailing plus one follow-up mailing yielded a 72.6% (n = 472) response rate. Examination of the returned surveys disclosed that 26.3% of the respondents had personally experienced one or more forms of sexual harassment in their work settings. The most frequently reported types of sexual harassment perpetrated by both employer and patient were, as defined by Cooper, "aesthetic appreciation" and "active mental groping," followed by "social touching" and "sexual abuse," with "ultimate threat" reported least. Fifty-four percent of the harassed respondents (all women) indicated that they had been harassed by male dentists/employers, and 37.1% reported they had been harassed by male patients, with the remaining 8% harassed by coworkers and others. More severe types of harassment were perpetrated by dentists/employers. PMID- 1625002 TI - Effective smokeless tobacco intervention for dental hygiene patients. AB - This study was designed to test the effectiveness of a smokeless tobacco (ST) intervention delivered in the oral healthcare office setting. A total of 518 male ST users were identified by questionnaire in clinic waiting rooms and then randomly assigned to either a usual-care control group or a special intervention group. Dental hygienists took the primary role in delivering the intervention, which consisted of a soft-tissue examination with special attention to oral lesions, advice to quit ST, distribution of self-help materials, a short video on why and how to stop using smokeless tobacco, and encouragement to set a quit date. Follow-up assessments conducted three months after the office visit showed that a significantly greater proportion of intervention group patients had stopped using ST (32% of the intervention group participants versus 21% of control group patients, kappa 2 = 8.03, p less than .01). The intervention protocol is described in detail so that dental hygienists may adapt it for use in their practice. PMID- 1625003 TI - Surgical repair of a craniofacial trauma patient: a case report. PMID- 1625004 TI - Pathophysiology and treatment of focal cerebral ischemia. Part I: Pathophysiology. AB - This article examines the pathophysiology of lesions caused by focal cerebral ischemia. Ischemia due to middle cerebral artery occlusion encompasses a densely ischemic focus and a less densely ischemic penumbral zone. Cells in the focus are usually doomed unless reperfusion is quickly instituted. In contrast, although the penumbra contains cells "at risk," these may remain viable for at least 4 to 8 hours. Cells in the penumbra may be salvaged by reperfusion or by drugs that prevent an extension of the infarction into the penumbral zone. Factors responsible for such an extension probably include acidosis, edema, K+/Ca++ transients, and inhibition of protein synthesis. Central to any discussion of the pathophysiology of ischemic lesions is energy depletion. This is because failure to maintain cellular adenosine triphosphate (ATP) levels leads to degradation of macromolecules of key importance to membrane and cytoskeletal integrity, to loss of ion homeostasis, involving cellular accumulation of Ca++, Na+, and Cl-, with osmotically obligated water, and to production of metabolic acids with a resulting decrease in intra- and extracellular pH. In all probability, loss of cellular calcium homeostasis plays an important role in the pathogenesis of ischemic cell damage. The resulting rise in the free cytosolic intracellular calcium concentration (Ca++) depends on both the loss of calcium pump function (due to ATP depletion), and the rise in membrane permeability to calcium. In ischemia, calcium influx occurs via multiple pathways. Some of the most important routes depend on activation of receptors by glutamate and associated excitatory amino acids released from depolarized presynaptic endings. However, ischemia also interfers with the intracellular sequestration and binding of calcium, thereby contributing to the rise in intracellular Ca++. A second key event in the ischemic tissue is activation of anaerobic glucolysis. The main reason for this activation is inhibition of mitochondrial metabolism by lack of oxygen; however, other factors probably contribute. For example, there is a complex interplay between loss of cellular calcium homeostasis and acidosis. On the one hand, a rise in intracellular Ca++ is apt to cause mitochondrial accumulation of calcium. This must interfere with ATP production and enhance anaerobic glucolysis. On the other hand, acidosis must interfere with calcium binding, thereby contributing to the rise in intracellular Ca++. PMID- 1625005 TI - Results of anterior temporal lobectomy that spares the amygdala in patients with complex partial seizures. AB - In December, 1980, the authors modified their anterior temporal lobectomies to exclude the amygdala from resection, a decision influenced by the dearth of pathology in the amygdala compared to the hippocampus. Furthermore, it had never been demonstrated that a good result was contingent upon including the amygdala per se in the lobectomy. Fifty-five (79%) of 70 patients in whom the amygdala was not resected were benefited by surgery. This result is similar to that achieved in series of anterior temporal lobectomies that include the amygdala in the resection. The results take on a special significance when considered together with those of amygdala-hippocampectomy which has been effective for controlling complex partial seizures of temporal mesiobasal origin (the region of the hippocampus, parahippocampal gyrus, and amygdala). A survey of the combined results strongly suggests that the anterior hippocampus and/or associated entorhinal cortex may be all that need be removed to control complex partial seizures caused by a temporal mesiobasal focus. PMID- 1625006 TI - Seizure outcome following standard temporal lobectomy: correlation with hippocampal neuron loss and extrahippocampal pathology. AB - The authors reviewed 149 patients who underwent standard anterior temporal lobectomies for intractable complex partial epilepsy with a mean follow-up period of 5 years. Quantitative analyses of hippocampal neuron loss showed that all patients had some cell loss compared to control hippocampi obtained at autopsy. The average hippocampal cell loss was categorized as severe (greater than 30% of autopsy control levels) or mild. Analysis of hippocampal and extrahippocampal pathologies showed that in 109 cases (73%, the hippocampal lesion group) hippocampal cell loss was mild in 17 cases (16%) and severe in 92 cases (84%); in the remaining 40 cases (27%, the extrahippocampal structural lesion group) hippocampal cell loss was mild in 24 cases (60%) and severe in 16 (40%). The first index of surgical outcome was worthwhile seizure reduction, which occurred in 94 cases (86%) with mild or severe hippocampal lesions and in 33 cases (82%) with extrahippocampal pathology. In the hippocampal lesion group, worthwhile seizure reduction occurred in 90% of cases with severe and in only 65% of cases with mild hippocampal cell loss (p = 0.015). In the extrahippocampal pathology group, worthwhile seizure was not statistically different, whether hippocampal cell loss was severe (94% of cases) or mild (75% of cases). The second index of surgical outcome was the occurrence of residual seizures in the patients with worthwhile seizure reduction, which would indicate remaining epileptogenic tissue. In the hippocampal lesion group, the incidence of residual seizures was not statistically different whether hippocampal cell loss was severe (24% of cases) or mild (45% of cases). However, in the extrahippocampal pathology group, residual seizures occurred in 53% of cases with severe cell loss (dual pathology) but in only 11% of cases with mild cell loss (p = 0.025). Worthwhile seizure reduction can be predicted by the presence of either severe hippocampal cell loss or an extrahippocampal structural lesion. However, residual seizures more frequently follow in cases with a combination of both (extrahippocampal pathology associated with severe hippocampal cell loss, or dual pathology), suggesting that epileptogenic tissue more likely extends outside the boundaries of a standard temporal lobectomy. PMID- 1625007 TI - Fentanyl-induced electrocorticographic seizures in patients with complex partial epilepsy. AB - Although electrical seizure activity in response to opioids such as fentanyl has been well described in animals, scalp electroencephalographic (EEG) recordings have failed to demonstrate epileptiform activity following narcotic administration in humans. The purpose of this study was to determine whether fentanyl is capable of evoking electrical seizure activity in patients with complex partial (temporal lobe) seizures. Nine patients were studied in whom recording electrode arrays had been placed in the bitemporal epidural space several days earlier to determine which temporal lobe gave rise to their seizures. The symptomatic temporal lobe was localized by correlating clinical and electrical seizure activity obtained during continuous simultaneous videotape and epidural EEG monitoring. In each patient, clinical seizures and electrical seizure activity were consistently demonstrated to arise unilaterally from one temporal lobe (four on the right, five on the left). During fentanyl induction of anesthesia in preparation for secondary craniotomy for anterior temporal lobectomy, eight of the nine patients exhibited electrical seizure activity at fentanyl doses ranging from 17.7 to 35.71 micrograms.kg-1 (mean 25.75 micrograms.kg-1). More importantly, four of these eight seizures occurred initially in the "healthy" temporal lobe contralateral to the surgically resected lobe from which the clinical seizures had been shown to arise. These findings indicate that, in patients with complex partial seizures, moderate doses of fentanyl can evoke electrical seizure activity. The results of this study could have important implications for neurosurgical centers where electrocorticography is used during surgery for the purpose of determining the extent of the resection. PMID- 1625008 TI - Arteriovenous malformations of the brain: choosing embolic materials to enhance safety and ease of excision. AB - The authors report their experience with surgical resection of 108 previously embolized arteriovenous malformations (AVM's). Embolization was performed via only transfemoral catheterization in 70 lesions and via the surgical exposure of feeding vessels in 32. The remaining six patients were referred for resection following silicone sphere embolization elsewhere. Materials used included polyvinyl alcohol (PVA) foam, platinum microcoils, detachable silicone balloons, surgical silk, a mixture of 33% ethanol and microfibrillar collagen, and isobutyl cyanoacrylate (IBCA). It is believed that proximal arterial occlusion with balloons is an inferior choice for preresection embolization, because the technical difficulty of placement is high and the nidus of the AVM is unaffected. Vascular coagulation and section and AVM retraction are more difficult with IBCA; therefore, this is also considered an inferior choice. Among the materials studied, the combination of PVA for distal occlusion and microcoils for proximal occlusion appears to be the superior choice. Fewer complications (stroke or hemorrhage) are seen when intraarterial Amytal (amobarbital) testing is used to guide the embolization. Data regarding toxicity, oncogenicity, and vascular metabolism or recanalization associated with PVA, IBCA, and n-butyl cyanoacrylate are reviewed. PMID- 1625009 TI - Symptomatic and functional outcome of stereotactic ventralis lateralis thalamotomy for intention tremor. AB - In the past, intention tremor has responded well to selected neuroablative procedures; however, objective symptomatic and functional outcomes of ventralis lateralis (VL) thalamotomy specifically for intention tremor in the post computerized tomography era has rarely been reported. This series explored the symptomatic and functional impact of VL thalamotomy on 14 patients presenting at the Mayo Clinic with severe, refractory intention tremor due to multiple sclerosis (five patients), trauma (four patients), or stroke (five patients). General neurological examinations, psychometric evaluations, speech pathology assessments, and neuroradiological scans were performed. Pre- and postoperative disability were graded according to a modified form of an established rating scale for tremor. All patients received VL radiofrequency thalamotomies utilizing neurophysiological recording and stimulation control. Contralateral targeted upper-extremity tremor remained symptomatically absent or markedly reduced in 81.8% of cases (mean follow-up period 23.4 months). The median disability score was reduced by 12 points (0.02 less than p less than 0.05). Persistent surgical morbidity was limited to two patients with mild, nondisabling dysarthrias. One elderly patient died of pulmonary complications 2 weeks postoperatively. There were no reported surgically induced exacerbations in multiple sclerosis; however, some of these patients exhibited difficulties with electrophysiological localization. These results compare favorably with those reported in the literature and confirm that stereotactic VL thalamotomy for debilitating intention tremor carries a low surgical risk and can be an effective treatment option for properly selected patients. PMID- 1625010 TI - Atretic cephalocele: the tip of the iceberg. AB - Atretic cephalocele appears as an unimportant and benign lesion. This malformation consists of meningeal and vestigial tissues (arachnoid, glial, or central nervous system rests). The authors report the findings in 16 cases (seven parietal and nine occipital) of rudimentary cephaloceles. Twelve patients presented with associated brain abnormalities detected by either computerized tomography (CT) or magnetic resonance imaging (MR). Nine lesions also exhibited an anomalous vascular component demonstrated by CT or MR imaging or at surgery. The existence of this tiny malformation in five cases was the main diagnostic clue to a severe complex of cerebral anomalies, namely cerebro-oculomuscular (Walker-Warburg) syndrome. An occipital location of the atretic cephalocele was associated with the worst prognosis, with only two children developing normally. However, a parietal location carried a better prognosis, which is contrary to the outcome reported in the current literature. The authors classify atretic cephaloceles into two types based on histological examination of the surgical specimens, and suggest that these types represent different stages in the development of this malformation. It is concluded that, in the evaluation of the atretic cephalocele, the neurosurgeon is obliged to proceed to a detailed neuroradiological study of the patient and that the prognosis does not depend on the existence of the cephalocele itself, but rather on associated "occult" brain anomalies. PMID- 1625011 TI - Intrathecal baclofen for spasticity of spinal origin: seven years of experience. AB - A total of 66 consecutive patients with severe spasticity of spinal cord origin were screened with intrathecal baclofen, and all but two responded with a two point decrease in their Ashworth spasticity scale and/or spasm scale score. Of these, 62 elected to receive chronic intrathecal baclofen administration by means of an implanted delivery system. These patients have been followed for an average of 30 months (the first three for 81 months). Intrathecal baclofen has been well tolerated and all serious side effects were transient and have been managed by dose adjustments. The pump presently available has worked safely; the only problem has been stalling in 7% of these devices. The catheter system has had to be repaired in just over one-half of the patients and is the main cause of interruption of drug delivery. Of the 62 patients implanted, 52 (84%) continue to be treated adequately for spasticity; there are three poor long-term responders, four deaths due to underlying disease, and three whose participation has been voluntarily withdrawn. It is suggested that long-term control of spinal spasticity by intrathecal baclofen can be achieved in most patients. PMID- 1625013 TI - On spinal osteochondromas. AB - Osteochondromas (or osteocartilaginous exostoses) make up about 30% to 40% of benign bone tumors. Most are solitary lesions but some are multiple, usually with autosomal dominant inheritance. From 1% to 4% of osteochondromas occur in the spine, where they can cause a variety of signs and symptoms, including those of spinal cord or spinal root compression. The authors present five patients with osteochondromas of the spine and review the findings together with those of over 130 cases reported since 1907. The cases were divided into: 1) spinal osteochondromas in patients with multiple osteochondromas, and 2) solitary osteochondromas occurring in the spine. The age (mean +/- standard error of the mean) of patients in the first group was 21.6 +/- 1.8 years compared to 30.0 +/- 2.1 years for those in the second group (p less than 0.02). There was a significant male predominance overall (M:F = 2.5:1; p less than 0.0005). In both groups, one-half of the lesions involved the cervical spine. Symptoms are caused by pressure on adjacent structures. Spinal cord compression was reported more than twice as frequently in the multiple osteochondroma group as in the single osteochondroma group (77% vs 33%; p less than 0.0005). Computerized tomography (CT) is the imaging procedure of choice. In both groups, the majority of surgically treated patients (90% and 88%, respectively) improve, with about three quarters of the improved patients having no residual disease or only minor deficits. PMID- 1625012 TI - Management of cervical spinal cord injury in ankylosing spondylitis: the intervertebral disc as a cause of cord compression. AB - Twenty-one patients with universal syndesmophytosis due to ankylosing spondylitis were identified in a consecutive series of 1578 patients with acute spine and spinal cord injuries. They were predominantly male, older than spinal cord injured patients in general, and most were injured by falls. Approximately one half were managed by halo-vest immobilization alone with good clinical and radiological outcomes. The remainder required surgery either for recurrent dislocation or for spinal cord compression associated with neurological deterioration. Extradural hematoma, a recognized cause of spinal cord compression in ankylosing spondylitis patients with spinal fractures, was encountered in two patients. Herniated intervertebral disc as a cause of spinal cord compression in ankylosing spondylitis does not appear to have been previously reported and was recognized three times in the present series, once in association with extradural hematoma. The pathology of ankylosing spondylitis is such that the nucleus pulposus tends to be spared, allowing disc herniation to occur in the heavily ossified spine. In virtually all patients, satisfactory correction of the flexion deformity could be safely accomplished following spinal fracture. It is concluded that fracture/dislocations of the cervical spine should be managed initially by halo-vest immobilization, without prior traction and with careful incremental correction of flexion deformity. Decompression is performed as required for extradural hematoma or intervertebral disc herniation, and internal fixation is carried out for recurrent dislocation. PMID- 1625014 TI - Loss of cerebral regulation during cardiac output variations in focal cerebral ischemia. AB - Focal cerebral ischemia was induced in anesthetized macaque monkeys by unilateral middle cerebral artery occlusion. The effect of blood volume expansion by a colloid agent and subsequent exsanguination to baseline cardiac output (CO) on local cerebral blood flow (CBF) was measured by the hydrogen clearance technique in both ischemic and nonischemic brain regions. Cardiac output was increased to maximum levels (159% +/- 92%, mean +/- standard error of the mean) by blood volume expansion with the colloid agent hetastarch, and was then reduced a similar amount (166% +/- 82%) by exsanguination during the ischemic period. Local CBF in ischemic brain regions varied directly with CO, with a correlation coefficient of 0.89 (% change CBF/% change CO), while CBF in nonischemic brain was not affected by upward or downward manipulations of CO. The difference in these responses between ischemic and nonischemic brain was highly significant (p less than 0.001). The results of this study show a profound loss of regulatory control in ischemic brain in response to alterations in CO, thereby suggesting that blood volume variations may cause significant changes in the intensity of ischemia. It is proposed that CO monitoring and manipulation may be vital for optimum care of patients with acute cerebral ischemia. PMID- 1625015 TI - Aneurysm recurrence following endovascular balloon occlusion. AB - Endovascular balloon occlusion is an alternative treatment for surgically unclippable cerebral aneurysms. The results of aneurysm occlusion with either a silicone or a latex balloon in a common carotid artery bifurcation aneurysm model are compared to determine which type of balloon was least likely to result in aneurysm recurrence. Five rabbits each underwent endovascular balloon occlusion with either a silicone or a latex balloon, with seven rabbits serving as controls. At 3 months postocclusion, nine of the 10 balloon-treated aneurysms had recurred. The recurrent aneurysm tended to be larger in animals treated with silicone than with latex balloons. A dense fibrotic response was present around the collar of the latex balloons, but no significant fibrotic response was found in the silicone balloon group. This study suggests that with currently available balloons, the initial complete angiographic obliteration of an aneurysm following balloon occlusion should not be interpreted as a cure and that periodic follow-up angiography should be performed. PMID- 1625017 TI - Oxyhemoglobin stimulation of endothelin production in cultured endothelial cells. AB - Oxyhemoglobin and endothelin have both been linked to the development of the severe and sustained cerebral vasospasm associated with subarachnoid hemorrhage. The effects of oxyhemoglobin on endothelin biosynthesis in cultured endothelial cells were evaluated. Oxyhemoglobin (0.01 to 100 microM) produced concentration dependent increases in immunoreactive endothelin levels in bovine pulmonary artery endothelial cell-conditioned medium. The median effective concentration for oxyhemoglobin-induced increases in immunoreactive endothelin levels was approximately 0.5 microM, and the maximum stimulation of immunoreactive endothelin levels was approximately 5.5-fold over basal conditions. In addition to directly stimulating basal production of immunoreactive endothelin, oxyhemoglobin significantly augmented immunoreactive endothelin production following platelet-mediated stimulation of endothelin production. An l-arginine analog inhibitor of nitric oxide synthase, L-NG-monomethyl arginine (L-NMMA, 200 microM), did not significantly affect basal immunoreactive endothelin levels. However, L-NMMA significantly augmented platelet-induced immunoreactive endothelin production. Methylene blue (10 microM), an inhibitor of soluble guanylate cyclase, did not significantly affect basal immunoreactive endothelin levels, nor did it significantly affect the platelet-mediated stimulation of immunoreactive endothelin production in cultured endothelial cells. The present results reveal that oxyhemoglobin can directly stimulate endothelin biosynthesis in cultured endothelial cells. This newly identified property of oxyhemoglobin suggests a potential mechanism for the sustained and severe cerebral vasospasm associated with subarachnoid hemorrhage. PMID- 1625016 TI - Cytokines and immunoregulatory molecules in malignant glial neoplasms. AB - Cytokines are important regulatory proteins controlling growth and differentiation of normal and malignant glial cells. Astrocytes and microglial cells produce and respond to many of the same cytokines employed by cells of the immune system. The authors have analyzed 15 histologically confirmed malignant glial neoplasms for the presence of infiltrating lymphocytes, macrophages, cytokines, and other immunoregulatory molecules using a panel of specific monoclonal and polyclonal antibodies on frozen-tissue sections. All neoplasms showed focal T-cell infiltration with CD8 cells predominating. Infiltration of activated macrophages (positive for CD11c, class II, and interleukin-2 receptor) was marked in all tumors. Within the neoplasm, tumor necrosis factor-alpha (TNF alpha)- and interleukin (IL)-6-positive macrophages were prominent in five cases, while the tumor cells themselves were only weakly positive. In the other 10 cases, the numerous infiltrating macrophages were only rarely immunoreactive for TNF-alpha or IL-6. Transforming growth factor-beta (TGF-beta) immunoreactivity was most prominent in those tumors with little TNF-alpha-positive macrophage infiltration, although intratumoral variability was present. This study suggests that, in malignant gliomas, the cytokines TNF-alpha and IL-6, although weakly present in neoplastic cells, are most prominent in infiltrating macrophages and in those regions of the tumors that show little immunoreactivity for TGF-beta. The important interactions among neoplastic, reactive glial, and inflammatory cells, which regulate tumor growth, are likely to be in part mediated through these molecules. PMID- 1625018 TI - A morphological and ultrastructural investigation of normal mouse brain tissue after intracerebral injection of tumor necrosis factor. AB - Morphological and ultrastructural changes in normal mouse brain tissue were investigated after intracerebral stereotactic injections of tumor necrosis factor (specific activity: 2.0 x 10(6) U/mg protein) into the right frontal lobe. The mice received either a single infusion or multiple tumor necrosis factor infusions in three different dose groups (10, 100, or 500 U). Compared with sham treated control mice that received adjusted intracerebral injections of purified albumin, the tumor necrosis factor-treated mice in all dose groups did not show any specific in vivo behavioral abnormalities during the 2 months of study following the infusions. Histological studies revealed hemorrhage attributable to the mechanics of the intracerebral infusions, a thickening of the arachnoid membranes, a reactive gliosis, and neutrophilic and/or mononuclear cell infiltration along the infusion pathway. A local neutrophilic response was prominent 1 day after tumor necrosis factor injection. An immunohistochemical analysis indicated that the mononuclear cell infiltration consisted of lymphocytes and macrophages. Except for the transient neutrophilic infiltration, these histological alterations did not differ from those seen in the sham-treated control groups, and most nonspecific reactive changes disappeared within 8 weeks after the injections. Furthermore, an ultrastructural study showed no apparent pathological changes in the cytoplasmic organelles of neuronal, glial, and endothelial cells in the tumor necrosis factor-injected mouse specimens. These results suggest that the tumor necrosis factor injections caused no specific toxicity and did not alter the parenchymal and stromal cells comprising normal mouse brain tissue. PMID- 1625019 TI - Diffuse leptomeningeal involvement by a ganglioglioma in a child. Case report. AB - Gangliogliomas are tumors composed of neuronal and glial elements that typically grow slowly by expansion only. This report describes a 20-month-old girl with a ganglioglioma that extensively involved the subarachnoid space; microscopic foci of tumor were found in the brain and spinal cord. Despite chemotherapy and radiation therapy, the child died 5 months after diagnosis. Molecular genetic analysis showed loss of chromosome 17p DNA sequences in the tumor tissue. PMID- 1625020 TI - Chiari malformation with compression of the medulla oblongata by the vertebral arteries. Case report. AB - A unique case is reported of Chiari malformation and compression of the medulla oblongata by both vertebral arteries. A 39-year-old woman complained of unsteady giant and motor weakness of the legs, and magnetic resonance imaging revealed the malformation and compression. Vascular decompression of the vertebral arteries was performed using synthetic (Gore-tex) vascular strips following posterior fossa decompression. PMID- 1625021 TI - Two fluid-blood density levels in chronic subdural hematoma. Case report. AB - The case of a chronic subdural hematoma is presented in which the computerized tomography scan showed two parallel fluid-blood density levels. The authors emphasize the importance of this finding in the management of such cases. PMID- 1625022 TI - Ruptured dermoid tumor of the cavernous sinus associated with the syndrome of fat embolism. Case report. AB - The syndrome of fat embolism is a well-known clinicopathological entity that may appear 2 to 4 days after skeletal trauma; nontraumatic causes have been recognized, however. This report details the fat embolism syndrome occurring in a patient after surgery within the cavernous sinus to remove a dermoid tumor. PMID- 1625023 TI - Suction control attachment for ultrasonic aspirators. Technical note. AB - A hand control to regulate suction has been developed and refined for use with ultrasonic aspirators. The instrument and its use are described. PMID- 1625024 TI - Barnes Hospital and the Washington University Medical Center. AB - The author documents the development of the Medical School at Washington University since 1891, when the St. Louis Medical College was first included as part of the University. In 1909, Robert Brookings, President of the Corporation of Washington University, acquired a large endowment and moved the clinical and hospital facilities to a new location, enabled by the estate of Robert Barnes. Harvey Cushing was offered the chair of surgery but eventually decided in favor of Harvard University in 1910. Dr. Ernest Sachs was recruited to Washington University by Dr. Fred Murphy, and in 1919 became the first ever Professor of Neurological Surgery. The history of neurosurgery and those who served it at the Washington University Medical Center and Barnes Hospital is recounted. PMID- 1625025 TI - Methylprednisolone for spinal cord injury. PMID- 1625026 TI - Methylprednisolone for spinal cord injury. PMID- 1625027 TI - Comparability of vasospasm in primates. PMID- 1625028 TI - Cruciate paralysis. PMID- 1625029 TI - Periodontoid disc herniation vs. degenerated ligaments presenting as extradural mass. PMID- 1625030 TI - Periodontoid disc herniation vs degenerated ligaments presenting as extradural mass. PMID- 1625031 TI - Facial nerve decompression following a basilar skull fracture. PMID- 1625032 TI - Aortic lysosomal hydrolases and pathological alterations in hypertensive and/or atherogenic diet fed rhesus monkeys. AB - Aortic lysosomal enzyme activities have been evaluated in relation to the extent and severity of aortic atherosclerosis in rhesus monkeys to see the biochemical and pathological effects of renal hypertension in experimental atherogenesis. The frequency and size of atherosclerotic plaques in aortas of atherogenic diet fed and/or hypertensive monkeys were calculated and an overall score of aortic atherosclerosis was computed on the basis of the gamut of pathological findings in relation to the biochemical alterations. This overall score of atherosclerosis was found to be significantly (p less than 0.01) greater in animals of all experimental groups as compared to the controls. PMID- 1625033 TI - Post-vagotomy variations of gastric mucosal mast cells in the rat. AB - The effects of the vagus and its action on the mucosal mast cells (MMC) of the secretory portion of the rat stomach are analyzed by observing the consequences caused by subdiaphragmatic truncal vagotomy on the MMC in terms of cell count and degranulation over a period of four months. Observations showed a gradual decrease in the number of mast cells/mm2, an increase in the percentage of MMC in a state of degranulation, but the same number of degranulated cells/mm2. This suggests that the vagus controls both numerically and functionally the MMC population in the secretory portion of the rat stomach. PMID- 1625034 TI - Tissue binding pattern of plant lectins in benign and malignant lesions of thyroid. AB - N-acetyl D-galactosamine specific lectins were isolated from the seeds of Jack Fruit (Artocarpus integrifolia) and Winged bean (Psophocarpus tetragonolobus) and D-galactose specific lectin was isolated from peanut (Arachis hypogaea). These lectins were conjugated to Horse Radish Peroxidase (HRP) and were used to study the lectin binding properties of benign and malignant lesions of the thyroid. For comparison of the results 10 normal fresh autopsy specimens were included in the study. The Peanut lectin (PNL) and Jack fruit lectin (JFL) conjugates showed positive binding with the cells in different lesions, while Winged Bean Lectin (WBL), despite its having a common inhibitory sugar, showed no binding even after neuraminidase treatment. These lectins revealed difference in the composition of glycoconjugates of benign and malignant thyroid cells. The HRP conjugated JFL and PNL may be of use in distinguishing carcinomatous tissues from benign tissues which makes them potential tools in the differential diagnosis of thyroid lesions. PMID- 1625035 TI - Regenerative capacity of minced muscle tissue in newborn and adult guinea pigs. AB - Our data showed that the regenerative capacity of skeletal muscle in newborn guinea pigs was less than in adults. In newborn guinea pigs the active regeneration of muscle tissue was only observed during the 1st week after mincing of gastrocnemius muscle. The 14-day grafts were characterized by having smaller muscle fibers and greater amounts of interstitial connective tissue. Furthermore, the active growth of connective tissue was more pronounced. The grafts did not recover contractility. In 60 day grafts the ectopic formation of 2-3 bone cartilage nodules was observed. In adult guinea pig grafts the quantity of muscle tissue was twice as great as in newborns. Muscle tissue was formed throughout the graft, but no bone-cartilage nodules were present. All 60 day grafts contracted when the tibial nerve was stimulated, but this contractility was very weak. However, the reestablishment of neuromuscular junctions had occurred. The age characteristics of skeletal muscle regeneration were the same both in the term guinea pig and in the rat. PMID- 1625036 TI - A light and electron microscopic histochemical study on lectin binding to cells with high metastatic potential in Lewis lung carcinoma. AB - Lectin binding to tumor cells in tissue sections of nonmetastatic and metastatic murine Lewis lung carcinoma (LLC) was assessed by light and electron microscopy using a lectin-gold technique. Ulex europaeus agglutinin-I (UEA-I) and peanut agglutinin (PNA) showed no binding, whereas concanavalin A (Con A), soybean agglutinin (SBA), Dolichos biflorus agglutinin (DBA), Maclura pomifera agglutinin (MPA), and Ricinus communis agglutinin-I (RCA-I) bound equally to the transplanted sites and metastases. However, wheat germ agglutinin (WGA) bound to metastases more highly than to the transplanted sites and there was a statistically significant difference (P less than 0.01) between the transplanted sites and metastases with regard to pre-embedding method. The tumor cells binding to WGA clearly decreased in number after sialic acid pretreatment and were rich in more well-differentiated organelle. In the bromodeoxyuridine (BrdUrd) labeling in vivo, cell proliferation was greater in the metastatic sites than in the transplanted sites. The above findings suggest that glycoconjugates on the tumor cell surface are altered in the process of metastasis and correlate with metastatic potential and cell proliferation. PMID- 1625037 TI - An antigranulomatous effect of glycyrrhizin. AB - In our previous study, we reported that monocyte-activation inhibitory factor was produced by stimulated fibroblasts. We also previously found that glycyrrhizin (GL) had an ability to affect fibroblasts because the proliferation of human fibroblasts was increased by GL. In this study, we demonstrated that culture supernatants from the GL-stimulated fibroblasts inhibited the activation of normal human peripheral monocytes in vitro. Then, studies were performed to know whether GL affects fibroblasts to suppress the granuloma formation. Pulmonary granulomas were induced in guinea pigs by Sephadex beads. The formation of granulomas was significantly suppressed by intraperitoneal injections of GL. Thus, GL was shown to have antigranulomatous effects in vivo. PMID- 1625038 TI - Modulation of alpha interferon levels by AZT treatment in HIV-seropositive patients. AB - The effect of AZT on serum HIV p24 antigen and endogenous serum alpha interferon levels was studied in AIDS and ARC patients. Following administration of AZT there was a rapid decline in the serum levels of both HIV p24 antigen and alpha interferon. When AZT treatment was interrupted, the levels of both HIV p24 antigen and of interferon rapidly increased. These findings suggest that HIV or some other AZT sensitive microorganism is the inducer of interferon which is characteristically found in the serum of AIDS and symptomatic HIV infected patients. They also suggest that the rapid decline in interferon levels may underlie some of the symptomatic benefit that follows administration of AZT. PMID- 1625039 TI - Neurotoxic effects of platinum compounds in cultured dorsal root ganglion cells. AB - The neurotoxic cancer chemotherapeutic agent cis-diamminedichloroplatinum (II) (cis-platin) was tested in a model system of cultured embryonic chick dorsal root ganglion cells, in order to investigate cellular mechanisms of toxicity. At 7.5 ug/ml, the drug caused mild toxicity. At doses of 75 ug/ml, cis-platin was toxic to cultures in 6 hours, in both neuronal and non-neuronal cell populations. After 24 hours of incubation with 75 ug/ml cis-platin, there was extensive cell death. The trans isomer of the drug, trans-platin, was less toxic than cis-platin at similar doses, causing less severe damage to the cells as well as less cell death. With both drugs, abnormalities in patterns of nuclear staining were prominent, whereas neuronal cell membrane staining patterns were less affected. Both drugs seemed to affect non-neuronal cells to a greater extent than neurons. Ultrastructural findings with both drugs included nucleolar segregation; mitochondrial changes were nonspecific. In this in vitro system, both cis- and trans-platin are toxic. The toxicity appears to predominantly affect the nucleus, and to preferentially involve non-neuronal cells. PMID- 1625040 TI - The antagonistic effect of interferon-beta on the interferon-gamma-induced expression of HLA-DR antigen in a squamous cell carcinoma line. AB - We examined the effect of type I interferon (IFN) on IFN-gamma-induced HLA-DR antigen expression in A431 cells, a human squamous cell carcinoma line. A431 cells expressed HLA-DR antigen when stimulated with IFN-gamma, but not with IFN beta. Simultaneous addition of IFN-gamma and IFN-beta to A431 cells resulted in significantly decreased HLA-DR antigen expression when compared to treatment with IFN-gamma alone. Kinetic studies revealed that IFN-beta was required concomitantly or prior to stimulation with IFN-gamma in order to down-regulate expression of HLA-DR antigens. IFN-alpha also inhibited IFN-gamma-induced HLA-DR antigen expression in A431 cells. Analysis of cytoplasmic mRNA showed that simultaneous treatment of A431 cells with IFN-gamma and IFN-beta resulted in a marked decrease of the level of DR alpha specific mRNA when compared to a level reached after treatment with IFN-gamma alone. These results suggest that type I IFN antagonize the IFN-gamma-induced HLA-DR antigen expression in human keratinocyte system, and that this antagonistic effect of type I IFN is confirmed as evidenced by a change in HLA-DR mRNA levels. PMID- 1625041 TI - New observations on the distribution of an old and forgotten model of enteritis in rats. AB - Human serum injected intravenously into rats caused multiple foci of acute enteritis. The enteritis had a predilection for the antimesenteric side of the intestine and for the zones between circumferential vessels. Despite their antimesenteric location, Peyer's patches tended to be spared. The details of distribution suggest that a gradient related to intestinal blood flow plays a role in development of the enteritis. PMID- 1625042 TI - Empowering your dental team. PMID- 1625043 TI - Creating the building blocks to running a successful practice--a success story. PMID- 1625044 TI - Anterior maxillary trauma resulting in tooth loss: an alternate treatment. PMID- 1625045 TI - Direct reimbursement vs. conventional dental insurance. PMID- 1625046 TI - Current computer usage in Indiana dental practices. AB - A survey of Indiana dentists reveals that increasing numbers of dental practices are computerized. Computer hardware, software, and various functions within dental practices are identified. Furthermore, the survey indicates future anticipated computer usage and the growing need for personnel to be trained in computers. PMID- 1625047 TI - Dental assistants, radiology, and the Indiana Law. AB - This article reviews the rules, regulations, and procedures which enable dental assistants to become radiology certified in Indiana. Dental assistants must participate in an American Dental Association (ADA)-accredited program or an Indiana State Department of Health (ISDH, formerly the Indiana State Board of Health)-approved on-the-job training program to qualify for the radiology certification examination. PMID- 1625048 TI - Sexual harassment. PMID- 1625049 TI - Sexual harassment. Looking at the law. PMID- 1625050 TI - Infectious waste disposal. PMID- 1625051 TI - The challenge of dental advertising: Oregon and the nation. PMID- 1625052 TI - Senior access program. PMID- 1625053 TI - A treatment rationale for periodontal prosthesis (it's simple, but not easy). PMID- 1625054 TI - GB (guanidinobenzoatase) cell surface protease and serum inhibitors in colorectal neoplasia. AB - Cell surface proteases and their inhibitors are functionally related to the invasive properties and metastatic potential of tumour cells. Epithelial cells of the colorectal mucosa possess a cell surface protease referred to as guanidinobenzoatase (GB), which is similar, if not identical, to plasminogen activator. GB exists in isoenzymatic forms, one of which is associated with epithelial cells of normal colorectal mucosa and of adenomatous polyps, whilst another isoenzymatic form is associated with colorectal adenocarcinoma cells. Normal serum contains inhibitor proteins which recognize the isoenzymatic form of GB found on normal and adenomatous polyp epithelial cells but this inhibitor does not recognize the isoenzymatic form of GB associated with adenocarcinoma cells. The fluorescent probe 9-amino-acridine locates cells possessing active GB in frozen sections of colorectal mucosa. A technique is described which enables colorectal carcinoma cells to be highlighted by fluorescence microscopy whilst normal epithelial cells are distinguished by their lack of fluorescence. This is of biological and possibly diagnostic significance. PMID- 1625055 TI - Reduction in apoptosis relative to mitosis in histologically normal epithelium accompanies fibrocystic change and carcinoma of the premenopausal human breast. AB - The aims of this study in 227 premenopausal women were (a) to determine the mitotic index (MI), the thymidine labelling index (LI), and the apoptotic index (AI) within the epithelial cells of histologically 'normal' human breast biopsy material removed away from the site of either a fibroadenoma or a carcinoma; and (b) to relate differences in the kinetic indices of the 'normal' epithelium to the pathology in the same breast diagnosed as fibroadenoma alone (125 patients), fibroadenoma with accompanying mild fibrocystic change (79 patients), or carcinoma (23 patients). Ratios of the average indices (AI/MI, AI/LI, MI/LI) were also calculated to minimize uncertainties related to the total cell population counted, the denominator in the LI, MI, and AI. All indices and ratios of indices were corrected for age, averaged over the cycle, and expressed as log-transformed values for analysis. Significant (P less than 0.001) reductions in AI and in apoptosis relative to mitosis (reduced AI/MI) were found in 'normal' epithelium from breasts having fibrocystic change (AI = 0.17 +/- 0.02; AI/MI = 1.01 +/- 0.18) and carcinoma (AI = 0.19 +/- 0.04; AI/MI = 0.88 +/- 0.29), compared with breast with fibroadenoma alone (AI = 0.27 +/- 0.03; AI/MI = 1.29 +/- 0.39). In the absence of significant differences in MI and LI between the 'normal' tissue groups, this finding raises the possibility that reduced epithelial cell apoptosis might be causally associated with the development of fibrocystic change and with an increased risk of development of carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625056 TI - Immunoelectron microscopy of cationized bovine serum albumin-induced glomerulonephritis in the rabbit. AB - Chronic immune complex glomerulonephritis was induced in a group of New Zealand white rabbits by daily intravenous injections of cationized bovine serum albumin (cBSA). The animals were serially killed and renal tissue was embedded in the hydrophilic resin Lowicryl K4M for immunoelectron microscopy. The results demonstrate the progressive deposition of rabbit IgG in the glomerular basement membrane in this model, with aggregation of immunoglobulins occurring only in the subepithelial space. Proteinuria developed concurrently with this event. Glomerular visceral epithelial cell (GVEC) endocytosis of immune material was observed at various stages of the disease process, suggesting that GVECs may be part of a clearance mechanism acting within the glomerulus. PMID- 1625058 TI - Diabetic glomerulosclerosis--immunogold ultrastructural studies on the glomerular distribution of type IV collagen and heparan sulphate proteoglycan. AB - We have undertaken an ultrastructural immunogold investigation of the distribution of type IV collagen and heparan sulphate proteoglycan (HSPG) in glomeruli from the kidneys of one normal control and three patients with diabetes mellitus and proteinuria. The sample included both diffuse and nodular diabetic glomerulosclerosis. In the control and diabetic kidneys, the type IV collagen was present predominantly on the endothelial aspect of the glomerular basement membrane (GBM), and by contrast the HSPG was found mainly on the epithelial side. In the mesangium in both control and diabetic glomeruli, type IV collagen was found predominantly in the central regions, while HSPG was mostly restricted to the region beneath the epithelial cells. Consequently, where there is a marked increase in mesangial matrix with nodule formation in diabetics there is a corresponding increase in the amount of type IV collagen but not of HSPG. Although the three diabetic patients were proteinuric, the HSPG was not decreased in the thickened GBMs. PMID- 1625057 TI - The effect of cyclosporin A on cationized bovine serum albumin-induced nephropathy in NZW rabbits. AB - The effect of cyclosporin A (CyA) was studied on the morphology and protein excretion of a rabbit chronic serum sickness nephritis using cationized bovine serum albumin (cBSA). One group of rabbits was given intravenous (i.v.) immunizing doses of cBSA and Escherichia coli endotoxin. One week later, these animals began a 6-week i.v. injection schedule of cBSA only. A second group followed the same injection protocol, but was given intramuscular (i.m.) CyA for 3 days prior to the immunizing dose of cBSA/endotoxin and throughout the subsequent cBSA schedule. A third group was given i.m. CyA only. Regular blood samples for CyA levels were taken from animals given the drug. Two 24-h urine samples were obtained from all animals in the study. Analysis of the blood samples showed that immunosuppressive levels of CyA were achieved after two i.m. doses of CyA. These levels were maintained during the course of the schedule. Morphologically, all rabbits completing the cBSA only injection schedule showed evidence of an immune-mediated glomerulopathy with variably severe membranous and endocapillary proliferative change. Less than half the rabbits in the cBSA/CyA group showed any evidence of membranous change. The glomeruli of animals given CyA only were normal. No morphological evidence of CyA toxicity was seen in any animal given the drug. The proteinuria profiles, however, suggested that as well as reducing protein excretion in rabbits given cBSA, CyA may interact with the immunizing dose of cBSA to produce an early, reversible, nephrotoxic effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625059 TI - Peripolar cells, granulated glomerular epithelial cells, and their relationship to the juxtaglomerular apparatus in malignant hypertension. AB - We have examined 12 autopsy kidneys from cases of malignant hypertension and compared them with normal controls. Peripolar cells and other granulated glomerular epithelial cells were counted in serial paraffin sections, and renin containing cells were quantified using an immunoperoxidase technique and a human renin antiserum. There were significantly more peripolar cells and other granulated glomerular epithelial cells in the cases of malignant hypertension. Most granulated glomerular epithelial cells were podocytes, situated at the periphery of the tuft. Peripolar cells correlated in number with other granulated glomerular epithelial cells and they had a similar distribution within the renal cortex, but there was no correlation between either of these cells and the number of renin-containing cells. There was hyperplasia of renin-containing cells in some juxtaglomerular apparatuses (JGAs), although the proportion of renin positive JGAs was unaltered. These results suggest that peripolar cells and other glomerular epithelial cells react in a similar way in malignant hypertension, but they do not support the hypothesis that peripolar cells are part of the JGA. PMID- 1625060 TI - Fabry's disease without angiokeratomas showing unusual eccrine gland vacuolation. AB - An unusual case of Anderson-Fabry's disease with renal damage and bilateral corneal deposits but without angiokeratomas is presented. Diagnosis was made by renal biopsy. Typical foamy transformation of endothelium, mesangium, tubular epithelial cells, vascular smooth muscle, and fibroblasts of kidney biopsy and similar changes of myoepithelial, perineural, and endothelial cells on the skin biopsy were observed. At electron microscopy, 'fingerprint-like' myelin figures were seen. The epithelial cells of eccrine sweat glands showed striking vacuolation but myelin figures were not seen. We suggest that electron microscopic study of skin biopsies is indicated in the evaluation of patients clinically suspected of having Fabry's disease. PMID- 1625061 TI - The ultrastructure of pulmonary arteries and arterioles in emphysema. AB - The lungs from three cases of pulmonary emphysema obtained at heart-lung transplantation were examined by electron microscopy to determine the origin of intimal longitudinal muscle and the formation of muscular tubes in small pulmonary arteries and arterioles. The earliest change consisted of migration of mature smooth muscle cells from the media of small pulmonary arteries, through gaps in the internal elastic lamina, into the subendothelial space. Most of these cells then adopted a longitudinal orientation, maintained a muscular phenotype, and became enmeshed in a web of elastic fibres. A small minority, immediately subjacent to the endothelium, were orientated circularly and, in some vessels, were enclosed by rudimentary internal and external elastic laminae to form early muscular tubes. Pulmonary arterioles, which are normally devoid of a media, contained several layers of circularly orientated smooth muscle cells, some of which also formed muscular tubes. It is postulated that the limited migration of mature smooth muscle cells seen in states of chronic hypoxia is mediated by a different stimulus from that causing the florid invasion of the intima by immature smooth muscle, with subsequent transformation into myofibroblasts, which characterize plexogenic pulmonary arteriopathy. PMID- 1625062 TI - Membranous expression of carcinoembryonic antigen (CEA) in the normal cervical squamous mucosa. AB - Using a panel of polyclonal and monoclonal antibodies to CEA-related antigens in paraffin-processed cervical biopsies, CEA and NCA expression has been demonstrated on the cell membrane of normal mature cervical squames. Cytofluorimetry of disaggregated cervical squames confirmed membranous expression and immunogold labelling of ultrathin cryostat sections localized CEA to the glycocalyx and to within cytoplasmic membrane-bound vesicles of mature squames. Immunoblotting of cervical tissue showed that most of the CEA reactivity was expressed as a glycoprotein of molecular weight around 180 k, probably CEA itself. Localization of the CEA to the cell membrane of mature cervical squames suggests a key role for these antigens in maintaining the integrity of the squamous mucosa, through the putative function of an adhesion molecule. PMID- 1625063 TI - In situ detection of oxidative stress in rat hepatocytes. AB - In rat hepatocytes in primary culture incubated with nitro blue tetrazolium, formazan content was increased by addition of t-butyl hydroperoxide, a potent oxidant, in a dose-related manner, but not by addition of valinomycin, which kills hepatocytes through mitochondrial damage. This increment after t-butyl hydroperoxide addition was not seen in hepatocytes preincubated with deferoxamine mesylate, a ferric iron chelator which inhibits radical formation. Liver perfusion with nitro blue tetrazolium and t-butyl hydroperoxide in rats produced formazan deposition faintly on the surface of hepatocytes throughout the liver and prominently in the cytoplasm of some hepatocytes, which was attenuated when performed following deferoxamine mesylate perfusion. When liver perfusion with nitro blue tetrazolium was performed in carbon tetrachloride-intoxicated rats, formazan deposition appeared diffusely in hepatocytes in the centrilobular areas. Similar deposition was also observed on the surface and in the cytoplasm of hepatocytes in the periportal and mid-zonal areas in rats undergoing post ischaemic reperfusion. Liver perfusion with nitro blue tetrazolium can detect in situ oxidative stress in hepatocytes and may be a useful tool for studying the role of lipid peroxidation in rat liver injury. PMID- 1625064 TI - Optimization of non-isotopic in situ hybridization on formalin-fixed, paraffin embedded material using digoxigenin-labelled probes and transgenic tissues. AB - The sensitivity of non-isotopic in situ hybridization (NISH), particularly on formalin-fixed, paraffin-embedded (FFPE) clinical tissues, has been the subject of controversy. Generally, NISH has been regarded as being less sensitive than radiolabelled procedures, although some reports have contradicted this. Accordingly, tissues from mice which were transgenic for variable amounts of the human alpha-1-antitrypsin gene were used to optimize the NISH procedure and to estimate the sensitivity. This approach showed that prolonged incubation of slides in final substrate resulted in high sensitivity--about 13 kb of target DNA. However, this prolonged incubation crucially depended on achieving minimal non-specific background staining. Many factors affected the degree of background staining, but five were particularly important. First, the method of mounting cut sections onto slides. Second, the length of the probe (ideally less than 400 bp). Third, the procedure for proteolytic digestion. Fourth, the denaturation technique, and fifth, the quality of the dextran sulphate used in the hybridization mix. The optimized protocol showed variable patterns of mRNA distribution in the transgenic mouse livers, while DNA distribution appeared uniform. PMID- 1625065 TI - Fatty acid oxidation disorders: a new class of metabolic diseases. PMID- 1625066 TI - Effects of neonatal polycythemia and hemodilution on capillary perfusion. AB - The effects of neonatal polycythemia on nutritive capillary perfusion were investigated by a television microscopy technique. The capillary blood flow velocity in skin was measured in 12 neonates with polycythemia before and after treatment with hemodilution, and in 13 healthy control infants. The capillary blood flow velocity in the patients was 0.11 (0.02 to 0.34) mm/sec and in the healthy control infants 0.30 (0.17 to 0.44) mm/sec (p less than 0.01, median and range values). In relation to the absolute hematocrit change after treatment range, -20% to 0%), the capillary blood flow velocity increased nonlinearly (range, +733% to -14%; r = -0.98; p less than 0.001). The postnatal age was found to contribute significantly to the variation in results--the neonates with polycythemia studied during the first day of life had a very slow skin capillary circulation and responded to treatment with a more pronounced increase in capillary blood flow velocity than did the older patients. This in vivo model for capillary perfusion indicates that an insufficient microcirculation may be involved in the pathophysiology responsible for the morbidity associated with neonatal polycythemia. PMID- 1625067 TI - Iron deficiency of liver, heart, and brain in newborn infants of diabetic mothers. AB - Infants of diabetic mothers frequently have polycythemia, elevated serum erythropoietin concentrations, and decreased serum iron and ferritin concentrations, likely representing a redistribution of fetal iron into erythrocytes to support augmented fetal hemoglobin synthesis. We hypothesized that fetal liver, heart, and brain iron concentrations are also reduced in these infants. After obtaining autopsy tissue from infants who had died before 7 days of age, we measured liver, heart, and brain iron concentrations using atomic absorption spectrophotometry. Seven infants of diabetic mothers and seven gestational age-matched control infants were studied. All infants of diabetic mothers had pancreatic islet cell hyperplasia, indicating fetal hyperglycemia and hyperinsulinemia. Liver iron concentrations in the infants of diabetic mothers were 6.6% of control values (489.0 +/- 154.4 vs 7379.7 +/- 1473.8 micrograms/gm dry tissue weight (mean +/- SEM); p less than 0.001), heart iron concentrations were 43.9% of control values (124.7 +/- 20.5 vs 284.1 +/- 34.8 micrograms/gm dry tissue weight; p less than 0.002), and brain iron concentrations were 60.6% of control values (106.1 +/- 13.7 vs 175.2 +/- 10.7 micrograms/gm dry tissue weight; p less than 0.003). Heart and brain iron concentrations were directly correlated with liver iron concentrations (r = 0.80 for both; p less than 0.001) and indicated that hepatic iron was greater than 75% depleted before heart and brain iron reduction. We conclude that severely affected infants of diabetic mothers have reduced liver, heart, and brain iron concentrations. The role of tissue iron deficiency in the genesis of the abnormal clinical findings in these infants deserves further consideration. PMID- 1625068 TI - Unsuspected congenital heart disease in neonates receiving extracorporeal life support: a review of ninety-five cases from the Extracorporeal Life Support Organization Registry. AB - The purpose of this study was to determine the frequency of patients with congenital heart disease who were given extracorporeal life support (ECLS) for respiratory failure. Underlying congenital heart disease "masked" by respiratory failure occurred in 2%. The most frequent pre-ECLS diagnosis that "masked" congenital heart disease was persistent fetal circulation. Of neonates with a pre ECLS diagnosis of persistent fetal circulation, congenital heart disease was found in 56 (9%) of 623 patients. PMID- 1625069 TI - Impairment of lung diffusion capacity in Schonlein-Henoch purpura. AB - Twenty-nine children with typical Schonlein-Henoch purpura (SHP) were tested at the initial phase of the disease for respiratory function. Of the 29 patients, 28 had a decrease of lung transfer for carbon monoxide (TLCO) as measured by a steady-state method. Lung volumes and blood gas values were normal; slight radiologic signs of interstitial lung involvement were observed in 18 of 26 patients. There was a decrease in TLCO to 56.8% of normal values for height and gender and to 58.5% when normal values were volume-adjusted to functional residual capacity. In 19 of 25 patients, TLCO measurements were performed at 3 month intervals during follow-up. In all cases, normalization of TLCO values was observed only after complete clinical recovery from SHP. All children with persisting symptoms, even limited to microscopic hematuria or slight proteinuria, had low TLCO values. In one patient low TLCO during follow-up preceded a late relapse of SHP in the form of acute nephritic disease with characteristic IgA deposits on renal biopsy. We conclude that low TLCO in SHP is probably related to alteration of the alveolar-capillary membrane by circulating immune complexes. This noninvasive technique may be useful in diagnosis, and during the follow-up of the disease as an early indicator of reactivation. PMID- 1625070 TI - Effect of acute versus chronic intoxication on clinical features of theophylline poisoning in children. AB - OBJECTIVES: To determine whether the method of intoxication influences the metabolic disturbances and pattern of life-threatening events that occur after theophylline intoxication in children. METHODS: Five-year prospective observational study of consecutive pediatric patients referred to a regional poison control center with a theophylline concentration (theo) greater than or equal to 30 micrograms/ml. At the time of referral, intoxication was categorized as acute (single toxic exposure), chronic (long-term toxic exposure), or acute-on therapeutic (single toxic exposure superimposed on maintenance therapy). RESULTS: One-hundred twenty-five patients were monitored. Mean age was 12 years (range, 3 days to 20 y). Seventy-four patients (59%) had acute intoxication, 31 (25%) had chronic intoxication, and 20 (16%) had acute-on-therapeutic intoxication. Mean peak serum (theo) was 55 micrograms/ml. Life-threatening events occurred in 12 patients (10%). Patients with acute intoxication had a significantly lower serum potassium level (3.04 vs 3.80 mmol/L; p less than 0.001) and higher serum glucose level (10.8 vs 7.0 mmol/L (194 vs 127 mg/dl); p less than 0.001) than did children with chronic intoxication. Although life-threatening events (seizures or arrhythmias) occurred at a similar rate across categories, the (theo) at which these events occurred was significantly higher in patients with acute intoxication than in those with chronic intoxication (100 vs 42 micrograms/ml; p = 0.02). Among children with chronic intoxication, those who had life-threatening events had (theo) similar to those who remained well (42 vs 47 micrograms/ml) but were significantly younger (1.6 vs 8.0 years; p less than 0.001). CONCLUSIONS: These data indicate that method of intoxication has significant effects on the metabolic and clinical consequences of theophylline poisoning. Life-threatening events occur in those with acute theophylline intoxication at significantly higher (theo) than in those with chronic intoxication. After chronic intoxication, peak (theo) does not identify patients at risk for life-threatening events; young age appears to be the primary risk factor. These findings potentially complicate the management of theophylline poisoning, given the difficulty of extracorporeal drug removal in young infants. PMID- 1625072 TI - Primary and secondary amenorrhea associated with spironolactone therapy in chronic liver disease. AB - Women with severe liver disease often have amenorrhea that resolves as liver disease abates. We describe three patients with mild to moderate chronic liver disease and amenorrhea. In each case amenorrhea resolved when spironolactone therapy was discontinued. We suggest that spironolactone, an androgen inhibitor, may also cause reversible amenorrhea. PMID- 1625071 TI - Heparin-induced thrombocytopenia in a child. AB - We describe a case of thrombocytopenia and deep venous thrombosis in a boy who received heparin to maintain patency of a central venous catheter. Measurement of the release of serotonin labeled with carbon 14 confirmed the presence of heparin induced thrombocytopenia. Children receiving heparin therapy should be monitored for the possibility of heparin-induced thrombocytopenia. PMID- 1625073 TI - Complications of immunosuppression. PMID- 1625074 TI - Unforgettable patients. PMID- 1625075 TI - Diagnosis of Lyme disease in children. PMID- 1625076 TI - Laboratory studies in neonates at risk for sepsis. PMID- 1625077 TI - Prevalence of congenital heart disease in patients with phenylketonuria. PMID- 1625078 TI - Urinary calcium excretion and nonsteroidal antiinflammatory treatment. PMID- 1625079 TI - Screening for glucose-6-phosphate dehydrogenase deficiency. PMID- 1625080 TI - Diagnosis of mitochondrial encephalomyopathies. PMID- 1625081 TI - Testing of bronchoalveolar lavage for the laboratory diagnosis of respiratory syncytial virus infections. PMID- 1625082 TI - Testing of bronchoalveolar lavage for the laboratory diagnosis of respiratory syncytial virus infections. PMID- 1625083 TI - Maternal smoking in early childhood: a risk factor for bronchial responsiveness to exercise in primary-school children. AB - The relationship between maternal smoking and bronchial hyperresponsiveness as assessed by a standardized free running test was investigated in a cohort of 1812 primary-school children in first grade. A child's exposure to maternal smoking during pregnancy, the first year of life, and the study year was recorded. Current exposure was not positively associated with bronchial hyperresponsiveness. The prevalence of this disorder was higher when maternal smoking during the child's first year of life was reported (9%) than when it was not (5.9%). The odds of being hyperresponsive were significantly higher in children exposed to maternal smoking in their first year of life (odds ratio, 2.82; 95% confidence interval, 1.25 to 6.34; p less than 0.01), especially in children with asthma (odds ratio, 20.55; 95% confidence interval, 2.5 to 168.9; p less than 0.01). Current exposure to maternal smoking was associated with less hyperresponsiveness. The effect of current maternal smoking might reflect changes in smoking habits by mothers of children with symptoms, whereas exposure to tobacco smoke in early life might be causally related to bronchial hyperresponsiveness. Our findings support the general hypothesis that early lung injuries have an impact on the later respiratory health of children. PMID- 1625084 TI - Intrapartum asphyxia and cerebral palsy. PMID- 1625085 TI - Growth of breast-fed infants. PMID- 1625086 TI - Chiropractic manipulation in children. PMID- 1625087 TI - Timing of the booster dose with Haemophilus polyribosylribitol phosphate conjugated with Neisseria outer-membrane protein. PMID- 1625088 TI - Correlation between serum immunoglobulin A concentrations and allergic manifestations in infants. AB - We studied the relationship of serum levels of IgA and IgE to allergic manifestations and otitis media in a cohort of 179 Icelandic children, aged 18 to 23 months. Only one of the infants had IgA deficiency (less than 50 micrograms/ml); all the others had IgA levels that were normal for their age. The children were divided into three groups according to their IgA levels (lowest 25%, intermediate 50%, highest 25%) and the clinical findings analyzed accordingly. The cumulative incidence of definite allergic manifestations was 37%. Asthma and otitis media were significantly more common among the infants with low normal IgA levels than among those with intermediate to high IgA levels. There was also a significant association between the severity of allergic manifestations and low IgA levels (p = 0.002). Children with detectable IgE (greater than or equal to 0.23 kilounit/L) had a higher incidence of atopic manifestations than did children in whom IgE was not detectable, but only a weak correlation was found between the occurrence and extent of allergic symptoms and increasing amounts of IgE beyond the 0.23 kilounit/L level. These findings suggest that atopic manifestations in infants may be more dependent on delayed maturation of IgA production than on overproduction of IgE. PMID- 1625089 TI - Hematologic predictors of bone marrow recovery in neutropenic patients hospitalized for fever: implications for discontinuation of antibiotics and early discharge from the hospital. AB - We evaluated the timing and pattern of changes in the complete blood cell count that preceded marrow recovery during 107 consecutive episodes of fever and neutropenia in 64 children with cancer. Four measures derived from serial daily measurement of the complete blood cell count were evaluated: total leukocyte count, absolute neutrophil count, absolute phagocyte count, and platelet count. During 70 (65%) of these 107 episodes, patients were discharged with an absolute neutrophil count of fewer than 500 cells/mm3; 24 patients were discharged from the hospital despite an absolute neutrophil count of fewer than 100 cells/mm3. During all but one of these 70 episodes, however, signs of early marrow recovery were present before discharge; sustained increases were observed in these patients' leukocyte, absolute neutrophil, absolute phagocyte, and platelet counts 2 or more days before their discharge in 41%, 49%, 50%, and 39% of cases, respectively. Although they were neutropenic at discharge, most patients had signs of multilineage marrow recovery at that time; 59 of 70 had increases in three of four of the measurements that we studied. None of the 69 patients who had evidence of marrow recovery at discharge had recurrence of fever. We conclude that children with cancer who were hospitalized for fever during periods of neutropenia have increases in the peripheral blood cell count that herald imminent bone marrow recovery, often several days before the absolute neutrophil count recovers to 500 cells/mm3. Our success in discharging such patients before resolution of neutropenia suggests that further controlled trials are needed to evaluate the safety and feasibility of cessation of antibiotic therapy and early discharge from the hospital. PMID- 1625090 TI - Relative value of diagnostic studies for von Willebrand disease. AB - Laboratory tests recommended to screen patients with mucosal bleeding for hemostatic disorders generally include determinations of prothrombin time, partial thromboplastin time, platelet count, and bleeding time. To determine the best tests to identify patients with von Willebrand disease (vWD), we reviewed the laboratory studies of 24 children with vWD and performed receiver operating characteristic analysis on the diagnostic studies. The vWD disease diagnostic tests included determinations of vWF activity (ristocetin cofactor activity), vWF factor antigen, and factor VIII procoagulant (VIII:c). The diagnosis of vWD required the presence of a personal and family history of bleeding symptoms and a documented abnormality of vWF activity or vWF antigen. vWF activity, vWF antigen, factor VIII:c and blood type were determined in 104 symptom-free children. There were no differences between patients and normal subjects for age, gender, or blood type. The bleeding time was abnormal in 43%, the partial thromboplastin time was abnormal in 25%, and either one or both were abnormal in 58% of the patients. The vWF activity, vWF antigen, and factor VIII:c were abnormal in 79%, 58%, and 33%, respectively. Receiver-operated-characteristic analysis showed the vWF activity to be superior to either the vWF antigen or factor VIII:c in establishing the diagnosis of vWD. The combination of the activity, bleeding time, and partial thromboplastin time successfully identified 92% of the patients as abnormal. Determination of vWF activity should be included routinely in the evaluation of hemostasis in children with symptomatic disease. PMID- 1625091 TI - Predictors of growth response to growth hormone in otherwise normal short children. AB - Sixty prepubertal short children (39 boys) with heights less than 2 SD for age and gender were treated daily for 1 year with recombinant human growth hormone (GH), either 0.1 IU/kg (group 0.1, n = 32) or 0.05 IU/kg (group 0.05, n = 28). Reserve of GH was determined by at least one GH provocative stimulus and 24-hour continuous blood withdrawal to determine the integrated concentration of GH (IC GH). All participants had a GH response to provocative tests greater than 10 micrograms/L. The height velocity (mean +/- SD) of the group as a whole increased from 4.46 +/- 1.02 to 7.59 +/- 1.65 cm/yr (p less than 0.001). The growth velocity of group 0.1 was significantly greater than that of group 0.05 (8.1 +/- 1.5 vs 7.0 +/- 1.65 cm/yr; p less than 0.01). Bone age did not advance more than 1 year during the treatment period. Growth velocity after 1 year of GH therapy was inversely correlated with the IC-GH in both groups, as was the pretreatment height velocity. We found no correlation of growth velocity during GH therapy with other measures such as parental heights, bone age/chronologic age ratio, maximal GH response to provocative tests, chronologic age, or pretreatment insulin-like growth factor I levels. We conclude that the best predictors for the 1-year growth outcome of short children with a normal GH response to provocative tests are the pretreatment growth velocity and the IC-GH. The short-term benefit from GH therapy in children with a normal growth velocity and a normal IC-GH is poor, whereas marked growth acceleration is noted in children with a low growth velocity and a low 24-hour IC-GH. PMID- 1625092 TI - Six-year results of a randomized, prospective trial of human growth hormone and oxandrolone in Turner syndrome. AB - Seventy girls with Turner syndrome, verified by karyotype, were randomly assigned to observation or treatment with human growth hormone (hGH), oxandrolone, or a combination of hGH plus oxandrolone for a period of 12 to 24 months, to assess the effect of treatment on growth velocity and adult height. Subsequently, all subjects received either hGH alone or hGH plus oxandrolone. Data are presented for 62 subjects treated for a period of 3 to 6 years. When compared with the anticipated growth rate in untreated patients, the growth rate after treatment with hGH, both alone and in combination with oxandrolone, showed a sustained increase for at least 6 years. Treatment is continuing in over half of the subjects; at present, 14 (82%) of 17 girls receiving hGH alone and 41 (91%) of 45 girls receiving combination therapy exceeded their expected adult heights. Thirty girls have completed treatment; mean height for these 30 patients is 151.9 cm, compared with their mean original projected adult height of 143.8 cm. We conclude that therapy with hGH, alone and in combination with oxandrolone, can result in a sustained increase in growth rate and a significant increase in adult height for most prepubertal girls with Turner syndrome. PMID- 1625093 TI - Human leukocyte antigen-DRB1*1104 in the chronic iridocyclitis of pauciarticular juvenile rheumatoid arthritis. AB - To determine whether genetic markers for chronic iridocyclitis could be identified, we used both serologic and oligonucleotide dot blot techniques to characterize immunogenetically 164 children with early-onset pauciarticular juvenile rheumatoid arthritis. Seventy-eight children (47.6%) had chronic iridocyclitis and 86 (52.4%) had not had evidence of eye disease during a mean follow-up period after the onset of arthritis of 15.8 years (minimum of 5.5 years). Control subjects were 218 healthy, unrelated individuals. The analysis was limited to alleles known to be associated with an increased or decreased risk of early-onset pauciarticular juvenile rheumatoid arthritis or of chronic iridocyclitis in this form of juvenile rheumatoid arthritis. Only one split of human leukocyte antigen (HLA)-DR5, HLA-DRB1* 1104, showed a statistically significant association with a risk of chronic iridocyclitis (chi-square value = 7.52; p = 0.036 adjusted; odds ratio 3.45); HLA-DQA1* 0501 and HLA-DQB1* 0301, both in linkage disequilibrium with HLA-DRB1* 1104, also were significantly associated with eye disease. Patients with both the DRB1* 1104 and DPB1* 0201 genes had a 7.7-fold increased risk for chronic iridocyclitis compared with that for other patients. The presence of HLA-DRB1* 1104 was about four times as specific, but only about one third as sensitive, as antinuclear antibodies in identifying patients at risk for eye disease. Although all children with early onset pauciarticular juvenile rheumatoid arthritis should undergo periodic slit lamp examinations, those with the HLA class II gene DRB1* 1104 are at particularly high risk for eye disease, and we recommend that they be monitored carefully for its evolution. PMID- 1625094 TI - Acquired cystic kidney disease before and after renal transplantation. AB - To determine the prevalence of acquired cystic kidney disease (ACKD), as reported in adults receiving long-term hemodialysis treatment, we studied 48 pediatric patients (aged 17 +/- 5.1 years) with end-stage renal disease by high-resolution ultrasonography or magnetic resonance imaging or both. Forty patients (83%) had a functioning renal transplant, with a mean transplant survival time of 3.4 years (range, 0.3 to 14.8 years); four patients were treated by hemodialysis and four by peritoneal dialysis. The mean duration of end-stage renal disease was 5.7 +/- 3.8 years. Ultrasonography detected ACKD in 12 (29%) of 42 patients, solitary cysts in 14 patients (33%), and no cysts in 16 patients (38%). In contrast, ACKD was diagnosed in only 3 of 37 patients studied by magnetic resonance imaging. In 31 patients studied by both imaging techniques. ACKD was diagnosed in three patients by magnetic resonance imaging but in 11 by ultrasonography. In patients with ACKD, the duration of end-stage renal disease was significantly longer, but renal (transplant) function was not different from that in patients with solitary cysts or no cysts. One patient with a history of 12 1/2 years of hemodialysis had multiple renal tumors that were diagnosed as renal cell carcinomas after bilateral nephrectomy. These results indicate that young patients with end-stage renal disease should be monitored regularly for the presence of ACKD, preferably by ultrasonography, even after successful renal transplantation. PMID- 1625095 TI - Contralateral renal abnormalities in multicystic-dysplastic kidney disease. AB - Multicystic-dysplastic kidney (MCDK) disease has been associated with contralateral genitourinary tract abnormalities; however, neither the nature nor the prevalence of the contralateral renal lesion has been delineated. We retrospectively studied patients with MCDK disease to determine the prevalence of contralateral renal abnormalities and of other urologic anomalies. Forty-nine patients, ranging in age from neonates to 6 years, were examined by renal ultrasonography, excretory urography or nuclear medicine scanning, and voiding cystourethrography; 51% of the patients had an associated urologic abnormality. The abnormality was contralateral to the MCDK in 19 patients (39%), ipsilateral in 3 patients (6%), and involved the bladder wall in 3 patients (6%). The most common contralateral genitourinary tract abnormality was vesicoureteral reflux (18%) followed by ureteropelvic junction obstruction (12%). We conclude that urologic anomalies are common in patients with MCDK disease; contralateral vesicoureteral reflux is the most common abnormality identified. PMID- 1625096 TI - Assessing the outcome of pediatric intensive care. AB - To describe the short-term outcome of pediatric intensive care by quantifying overall functional morbidity and cognitive impairment, I developed the Pediatric Overall Performance Category (POPC) and the Pediatric Cerebral Performance Category (PCPC) scales, respectively. A total of 1469 subjects (1539 admissions) were admitted to the pediatric intensive care unit of Arkansas Children's Hospital from July 1989 through December 1990. Patients were assigned baseline POPC and PCPC scores derived from historical information and discharge scores at the time of discharge from the hospital (or from the pediatric intensive care unit for patients with multiple hospitalizations). Delta scores were calculated as the difference between the discharge scores and the baseline scores. The changes in POPC and PCPC scores were associated with several measures of morbidity (length of stay in the pediatric intensive care unit, total hospital charges, and discharge care needs) and with severity of illness (pediatric risk of mortality score) or severity of injury (pediatric trauma score) (p less than 0.0001). Interrater reliability was excellent (r = 0.88 to 0.96; p less than 0.001). The POPC and PCPC scales are apparently reliable and valid tools for assessing the outcome of pediatric intensive care. PMID- 1625097 TI - Vitamin A levels in children with measles in Long Beach, California. AB - Studies from Africa suggest that vitamin A supplementation may reduce morbidity and mortality rates associated with measles among poorly nourished children. We studied 20 children with measles in Long Beach, Calif., and found that 50% (95% confidence interval; 28% to 72%) were vitamin A deficient. This frequency among presumably well nourished American children supports evaluation of vitamin A status as a part of acute management of measles in the United States. PMID- 1625098 TI - Glutaric aciduria type I: unusual biochemical presentation. AB - We describe a patient with glutaryl-coenzyme A dehydrogenase deficiency, demonstrated by a residual enzyme activity of only 1% in cultured fibroblasts. Although the clinical presentation was typical of glutaric aciduria type I, the urine concentrations of glutaric, glutaconic, and 3-hydroxyglutaric acids remained normal, even during episodes of clinical decompensation. An increased free glutarate level was demonstrated only in cerebrospinal fluid. PMID- 1625099 TI - Brain dysgenesis and congenital intracerebral calcification associated with 3 hydroxyisobutyric aciduria. AB - Monozygotic male twins born to nonconsanguineous parents had dysmorphic facial features, microcephaly, migrational brain disorder, and congenital intracerebral calcification. They excreted excessive amounts of 3-hydroxyisobutyric acid, a metabolite of valine, and had evidence of impaired oxidative metabolism and metabolic acidosis. The level of 3-hydroxyisobutyrate in stored samples of midtrimester amniotic fluid was found to be high. The association of 3 hydroxyisobutyric aciduria with brain dysgenesis is a newly recognized mendelian disorder; its recurrence in a family at risk is potentially avoidable by prenatal diagnosis. PMID- 1625100 TI - Familial pulmonary nodular lymphoid hyperplasia. AB - We describe three persons in one family with diffuse lung infiltrates, digital clubbing, and chronic hypoxia. Elevated immunoglobulin levels and antinuclear antibodies were found in all patients; pathologic findings included hyperplastic lymphoid follicles infiltrating the epithelium of the small airways. These cases may represent a familial systemic autoimmune disorder seen primarily with pulmonary compromise. PMID- 1625101 TI - Effect of high doses of human recombinant erythropoietin on the need for blood transfusions in preterm infants. AB - To determine whether prophylactic treatment with recombinant human erythropoietin (rHuEPO) and iron would reduce the need for blood transfusions, we randomly assigned 22 premature infants with gestational ages less than or equal to 32 weeks and birth weights less than or equal to 1.75 kg to receive rHuEPO, 400 IU/kg three times a week, plus iron, 20 mg/wk intravenously, from the second day of life (11 infants), or no rHuEPO and no iron (11 infants). The two groups had similar birth weights and clinical variables. The treated infants required fewer blood transfusions (0.8 +/- 1.5 vs 3.1 +/- 2.1; p = 0.01) and less volume of packed erythrocytes (14.2 +/- 25.9 vs 48.4 +/- 34.0 ml/kg; p = 0.02). The amounts of blood sampled were not different (19.5 +/- 21.1 vs 27.8 +/- 19.1 ml/kg; p = 0.35). Reticulocyte and hematocrit values were higher in the treated group (4.46% +/- 0.8% vs 1.49% +/- 1.1% (p = 0.0001) and 48.1% +/- 7.3% vs 43.8% +/- 4.7% (p = 0.004), respectively). No side effects of either rHuEPO or intravenously administered iron were noted. These data indicate that rHuEPO, in combination with iron supplementation, is effective in reducing the need for blood transfusions in the premature infant. More information is needed on dosage, timing, and iron and vitamin supplementation. PMID- 1625102 TI - The influence of manufacturing parameters on the formation and growth on autoclaving of a 40% V/V Bis-Perfluorobutylethene emulsion. AB - The influence of different process variables on the number of large particles before and after autoclaving of a 40% V/V Bis-Perfluorobutylethene emulsion stabilized by egg yolk lecithin, made isotonic with blood, was examined. The concentration of emulsifier, emulsification and autoclaving time and temperature, fill volume and the cooling gradient applied to the emulsion after autoclaving all affect the number of large droplets and hence the stability and acceptability of the finished product. This work suggests that validation of equipment and process to very exacting specifications and strict adherence to specified manufacturing protocol is essential for the reproducible production of fluorocarbon emulsions acceptable for intravenous administration. PMID- 1625103 TI - Preparation and stability of intravenous solutions of sodium dichloroacetate (DCA). AB - An IV injection formulation of sodium dichloroacetate (DCA) was prepared without heat sterilization, and examined for stability. DCA is heat labile in aqueous solutions. Its decomposition involves dehalogenation and production of hydrogen ions. Decomposition occurs relatively rapidly at relatively low pH values, and is promoted by heating. Injection solutions should be prepared aseptically and sterilized by filtration. Solutions prepared aseptically and sterilized by filtration are stable stored at 4 degrees C for at least four yrs. PMID- 1625104 TI - The insufficiency of single point diffusive air flow integrity testing. AB - Filter manufacturers characterize a given filter type by a single acceptable maximum diffusive air flow level. A too high value is prudently rejected as signalling the possible presence of flaws. Values lower than the stipulated maximum are accepted. However, the presence of single pores, whatever their sizes, is not being revealed. Only their influence within the total porosity is measured by the diffusive air flow. Single point diffusive air flow integrity testing may invite misleading conclusions because it offers possibilities for lower air flows to mask the presence of flaws or of outsized pores. This is particularly so where initial (prefiltration) and final integrity are being compared. The filtrative accretion of retained material, viable or not, must inevitably come to block or diminish the size of the pores. This results in decreased total porosity, directly expressed in lower diffusive air flow values. Sufficient drop in such final air flow values may mask the presence of a flaw developed in the filter subsequent to its initial testing. For this reason a filter's entire air flow permeation curve, particularly including its bubble point, must be characterized. It is this measurement, and this measurement alone, that is capable of unambiguously revealing the existence of insufficiently retentive pores. The inquiry into such presence is the very purpose of filter integrity testing. PMID- 1625105 TI - Apples, oranges, and additive assurance. PMID- 1625106 TI - Containment: comprehensive assessment and integrated control. PMID- 1625108 TI - FDA: keynote address, PDA/FDA Conference. PMID- 1625107 TI - Role of calcium and arachidonic acid metabolites in creatine kinase release from isolated rat skeletal muscles damaged by organic cosolvents. AB - The objective of the present work is to provide additional experimental evidence which can help to differentiate between a direct solubilization mechanism versus an intracellular calcium mechanism of organic cosolvent-induced creatine kinase release from isolated rat skeletal muscles. An increase in cytosolic free calcium levels following exposure to propylene glycol was evaluated indirectly through the measurement of skeletal muscle glycogen levels. Skeletal muscle glycogen levels decreased significantly in propylene glycol-treated muscles compared to normal saline-treated controls; providing further evidence for the possible role of increased cytosolic calcium in organic cosolvent-induced muscle damage. The possible involvement of prostaglandins and leukotrienes which disrupt membrane integrity leading to propylene glycol-induced creatine kinase release was investigated via the use of cyclo-oxygenase and lipoxygenase inhibitors. Organic cosolvent-induced creatine kinase release was not significantly reduced when the muscles were incubated in the presence of cyclo-oxygenase inhibitors, lipoxygenase inhibitors, or a combination of a cyclo-oxygenase and lipoxygenase inhibitor. These findings suggest that in this experimental system prostaglandins and leukotrienes do not seem to be involved in organic cosolvent-induced alterations in sarcolemma integrity leading to the release of creatine kinase. PMID- 1625109 TI - Achieving synergy and strength: an industry perspective on the Food and Drug Administration. PMID- 1625110 TI - Empirical calibration of light blockage sensors. AB - The intent of this note is to describe in more detail the calibration process for these sensors with particular emphasis on the method of obtaining the best calibration curve from the raw data. A new method of assessing the accuracy of the calibration curve is also described. PMID- 1625111 TI - Two-year follow-up of a social-cognitive intervention to prevent substance use. AB - This study presents two-year follow-up results of the Adolescent Decision-Making Program initially implemented when students were in their sixth grade. The intervention was found to maintain a positive effect on mean tobacco use, but no differences were observed for mean alcohol, marijuana, or hard drug use. In a test of the differential effectiveness of the intervention, program students living with married parents reported lower mean tobacco use than control students living with married parents and program and control students living with single parents. Logistic regression analyses examining the proportion of users at follow up revealed a negative program effect for alcohol and no differences for the other substances. Subsequent attrition analyses strongly suggested that the positive effect for tobacco use at follow-up was most likely even stronger, and that the negative effect for alcohol was spurious. The importance of examining both program and attrition effects when evaluating the impact of longitudinal preventive interventions was emphasized, and the need to consider alternative models to guide the conceptualization and evaluation of adolescent substance use prevention programs was discussed. PMID- 1625113 TI - Substance use among women at risk for HIV infection. AB - This article reports results from a survey of culturally diverse women at risk for HIV infection in south Florida. Data concerning their substance use and its association with HIV risk behaviors are presented. Results indicate levels of consumption which exceed expectations based on general estimates of female substance use. Further, substance use was associated with specific behaviors and lifestyles which placed the women at increased risk for HIV infection. PMID- 1625112 TI - Race differences in antisocial behaviors and attitudes and early initiation of substance use. AB - This article examines racial differences in self-reported delinquency, school trouble, antisocial attitudes, and toughness and in teacher-rated aggressive and inattentive behaviors among fifth grade black, white, and Asian American subjects. Also examined are the relationships of these variables to substance initiation within each racial group. Controlling for socio-economic status, racial groups differed from one another in self-reported delinquency, school trouble and toughness, and in teacher-rated aggressiveness and inattention. Antisocial behavior and attitudes were stronger predictors of substance initiation for Asian American than for black and white children. For white children both self-reported and teacher-rated behavior were significantly related to substance initiation. For black children, only self-reported antisocial behavior, and for Asian American children only self-reported delinquent behavior and attitudes predicted substance initiation. Implications for prevention and research are discussed. PMID- 1625114 TI - Student perceptions of the danger of drug use: a factor analysis. AB - Australian secondary school students from three Year levels were asked to rate the danger involved in various uses of alcohol, tobacco, inhalants, marijuana and other illicit drugs. These ratings were then factor analyzed for each Year level. The results showed a more refined discrimination among the older students, with type of drug and frequency of use being important considerations. Familiarity was a major consideration for the younger students. The cognitive factors derived from the data are consistent with expectations based on the gateway theory of drug use. PMID- 1625115 TI - Smoking education and prevention: a developmental model. AB - A developmental approach to smoking education and prevention for children and adolescents is proposed. Literature is reviewed concerning the most appropriate agent, content, and presentation, of anti-smoking education for each of three age groups: children to age ten, pre/early adolescents eleven to fifteen, and adolescents fifteen to eighteen. For children to age ten, it is suggested that parents are the best agents of education, with teachers, peers, and the mass media, also playing some role. For pre/early adolescents, peers are suggested as the best agents of education, building onto the earlier and ongoing work of the agents mentioned above. For adolescents, the role of the media hero-figure is discussed. It is emphasized that sources of influence may function additively in affecting the child or adolescent's decisions about smoking, and that education in each stage must build on the stage before. PMID- 1625117 TI - Chest injuries in children: an analysis of 100 cases of blunt chest trauma from motor vehicle accidents. AB - One hundred twenty-eight cases of chest injury were seen in a Paediatric Trauma Unit over a 5 1/2-year period. One hundred patients sustained motor vehicle accident (MVA)-related blunt chest injuries, 91 of them as pedestrians. Nine children had blunt chest injuries from falls, 10 had stab wounds (3 assault, 7 accidental), and 9 had gunshot injuries (6 from birdshot used by police during civil disturbance). MVA-related injuries were studied separately, as an etiologically homogeneous group. Sixty-five of these patients were under the age of 6. All but 3 also had serious extrathoracic injuries. The mean injury severity score (ISS) in MVA-related injuries was 25. Eight patients died, all with an ISS of 34 or more, 7 of whom had fatal head injuries. In MVA-related injuries, pulmonary contusion (n = 73) was the most frequent lesion seen, followed by rib fracture (n = 62), posttraumatic effusion (n = 58), pneumothorax (n = 38), and pneumatocele (n = 5). In MVA-related injuries, 18 children required ventilation. Thirty-nine (69%) of 56 children with radiologically evident posttraumatic pleural effusion had intercostal chest drainage. Analysis suggests that lung injury is a central event in MVA-related blunt chest trauma. Primary lung injury, radiologically visible as contusion, is complicated by hematoma, posttraumatic effusion, and pneumothorax. PMID- 1625116 TI - Bronchoscopy during the first month of life. AB - During the 6-year period from 1984 to 1989, 196 bronchoscopies were performed on 132 neonates. The indications were grouped into four categories: (1) difficulties in artificial ventilation or failure to wean the baby from the ventilator (52); (2) other respiratory difficulties (52); (3) audible stridor (16); and (4) routine preoperative or postoperative examination of esophageal atresia patients (12). The most common finding was laryngomalacia or tracheomalacia (31). Other findings were: obstructing tracheal or bronchial granulation or stricture (23), obstructing mucous plug (22), grave tracheobronchitis (11), tracheoesophageal H fistula (5), laryngeal perforation (3), congenital laryngeal stenosis (2), and complete laryngotracheoesophageal cleft (1). Four patients had miscellaneous pathology. The findings were normal in 30 patients. A therapeutic procedure was included in 99 of the 196 bronchoscopies. Seven serious complications occurred during the operative bronchoscopies, two of them requiring immediate pulmonary surgery. All complications were successfully managed. In contrast, no complications occurred in the 97 purely diagnostic bronchoscopies. In experienced hands, bronchoscopy of the newborn is a safe and useful examination. Complications occur when therapeutic procedures are included. Therefore, operative bronchoscopy should only be performed in conditions in which immediate thoracotomy and pulmonary surgery can be performed. PMID- 1625118 TI - Continuous paravertebral block for postthoracotomy analgesia in children. AB - Six children with a mean age of 10.6 years (range, 7 to 16 years) underwent thoracotomy for pulmonary and esophageal procedures. Postoperatively, continuous paravertebral block using an infusion of bupivacaine via an extrapleural catheter was used. Excellent analgesia was attained in all patients, with no requirement for opiates or other analgesic drugs. There were no pulmonary complications and no complications related to the continuous extrapleural infusion. We conclude that continuous paravertebral block is an effective and safe method for ++post thoracotomy pain relief in children. PMID- 1625119 TI - CHARGE and esophageal atresia. AB - CHARGE association was diagnosed in 61 infants, 20 of whom died, mainly during the first 2 years of life. Esophageal atresia and/or tracheoesophageal fistula were present in 10 neonates. Axial skeletal anomalies occurred in 7 of the 10, but none had preaxial limb defects typical of the VATER association. All had major cardiac anomalies, predominantly tetralogy of Fallot. The majority of patients had primary repair of the esophagus. The postoperative course was stormy in all patients, with a high incidence of complications and 70% died. The recognition of features of the CHARGE association is important because it has major prognostic and therapeutic implications. PMID- 1625120 TI - Prophylactic extrapleural chest drainage following repair of esophageal atresia: is it necessary? AB - In a review of 110 cases of esophageal atresia (EA) and tracheoesophageal fistula (TEF), 15 patients (13.6%) developed anastomotic leakage. All patients had extrapleural surgical exposure and prophylactic extrapleural chest drainage (PEPCD). Despite this precaution, all patients with anastomotic leaks developed a pneumothorax with or without a pleural effusion. This required insertion of an additional drain in 12 (80%) cases. PEPCD following repair of EA and TEF does not appear to prevent pneumothorax or pleural effusion when anastomotic leakage occurs. PMID- 1625121 TI - Reassessment of the end-to-side operation for esophageal atresia with distal tracheoesophageal fistula: 22-year experience with 68 cases. AB - End-to-side anastomosis (ES) and ligation of the tracheoesophageal fistula (TEF) has been the procedure of choice for esophageal atresia at our institution since 1967. This report summarizes our operative and long-term results with the ES operation in 68 babies, including 33 in Waterston group A (50%), 23 in group B (35%), and 12 in group C (15%). An additional 10 patients had a primary end-to end (EE) anastomosis, while 14 others required either staged EE repair or an esophageal replacement procedure. Overall survival rate with ES was 93% including two deaths attributed to major anastomotic leaks and sepsis, and three others in group C from cardiac anomalies. Six (9%) of those having ES anastomosis developed a recurrent TEF between 40 days and 21 months of age, necessitating reoperation. Predisposing factors to recurrent TEF were surgical inexperience (three cases; first operation for each surgeon), forceful vomiting secondary to gastroesophageal reflux (GER) in two, and drug overdose in one. Anastomotic leak occurred in seven (10%) following end-to-side repair and was implicated in two deaths. Three patients developed minor anastomotic stricture requiring less than three dilatations, while one with a tight stricture needed as many as five dilatations over the first 14 months of life. Mild dysphagia and respiratory symptoms were uniformly observed during the first year, but only five patients (7%), including the two with recurrent TEF, required fundoplication for persistent GER. All patients were eating table foods after 1 year of age, while 10 (15%) have required periodic endoscopic removal of solid food lodged at the radiographically unobstructed anastomosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625122 TI - Hypogastrinemia and esophageal atresia. AB - To investigate extraesophageal anomalies in infants with esophageal atresia, preoperative plasma gastrin was measured in 12 infants. The median plasma gastrin was 32 ng/L (interquartile range, 24 to 44). There was significant correlation with birth weight (rs = .73, P less than .05) and gestational age (rs = .74, P less than .05). Within this group 9 infants of greater than 36 weeks' gestation were matched to a group of 20 control infants without esophageal atresia. Infants with esophageal atresia had a significantly lower median plasma gastrin (38 ng/L v 55 ng/L, P less than .05). This may indicate preexisting vagal abnormalities in esophageal atresia unrelated to surgical intervention. PMID- 1625123 TI - Diagnosis and management of common bile duct stones in patients with sickle hemoglobinopathies. AB - Nine of 35 patients with sickle hemoglobinopathies and cholelithiasis were found to have concomitant common bile duct (CBD) stones. We describe the diagnosis and management of these patients with CBD stones. Historical information, physical examination, and routine laboratory tests were unable to identify accurately the patients with CBD stones. Similarly, ultrasonography of the hepatobiliary system was an insensitive method for detecting CBD stones, as only 3 of 8 patients were correctly identified. In contrast, both an intraoperative cholangiogram and endoscopic retrograde cholangiopancreatography were sensitive procedures for detection of CBD stones. We conclude that CBD stones are relatively common in patients with sickle cell disease and cholelithiasis, and clinicians should have a high index of suspicion for their presence. PMID- 1625124 TI - Double duodenal atresia/stenosis: a report of four cases. AB - Four neonates with double duodenal atresia/stenosis are described. Preoperative plain radiographs in two patients demonstrated atypical appearances suggestive of complex pathology. Cystic dilatation of the second part of the duodenum was observed at laparotomy in two patients and in one of these the "cyst" was palpable preoperatively, causing diagnostic confusion. All four patients underwent successful surgery but one infant with Down's syndrome subsequently died of congenital heart disease. PMID- 1625125 TI - Clinical use of the absorbable spleen net in stellate rupture of spleen in children. AB - This paper reports three cases of stellate rupture of the spleen in children treated by wrapping with the omentum, following the use of the absorbable spleen net (ASN), which is made of the ordinary surgical sutures. All patients were cured with spleen preservation. No complications occurred. PMID- 1625126 TI - Intestinal injuries in childhood: analysis of 32 cases. AB - This is a retrospective study of 32 cases of intestinal injuries sustained among 135 children admitted from cases of abdominal trauma in 1976 till 1989. Falls from height or bullock cart and bull-gore injury formed the majority of the cases (21/32; 65%). Clinical thermometer accounted for perforating injuries in 2 neonates. Penetrating injury accounted for 10 cases and blunt trauma was responsible in 19. The site of injury was duodenum 1, jejunum 8, ileum 17, colon 3, rectum 4, and multiple sites 1. Associated injuries included diaphragmatic rupture 1, liver 1, mesentery 4, retroperitoneal hematoma 4, head injury 2, and loss of hand due to blast 1. Diagnosis was made on history, physical examination, pneumoperitoneum in plain x-ray, and diagnostic four-quadrant peritoneal tap. Closure of perforations was done in 21 cases, wedge resection in 3, and resection anastomosis in 5. Protective colostomy had to be done in 5 cases. Four patients died of septicemia (2) and head injury (2). PMID- 1625127 TI - The necessity of prophylactic antibiotics in uncomplicated appendicitis during childhood. AB - A prospective, randomized, clinical study was done to evaluate the place of prophylactic antibiotics in uncomplicated childhood appendicitis. One hundred patients with uncomplicated appendicitis were randomly assigned to one of four groups, each consisting of 25 cases. Group 1 patients did not receive prophylactic antibiotic. Group 2, group 3, and group 4 patients received ornidazole, penicillin plus tobramycin, and piperacillin, respectively. The use of prophylactic antibiotics did not yield better results than the use of placebos. The rarity of infectious complications after uncomplicated appendicectomy may be unique for children. Although the need for antibiotic prophylaxis is well documented in adults, the rarity of infectious complications makes it highly questionable in the treatment of uncomplicated appendicitis in children. PMID- 1625128 TI - Perforation during hydrostatic reduction of intussusception: proposed mechanism and review of the literature. AB - Eight cases of children with intussusception in whom the bowel perforated during attempts at enema reduction are reviewed. Certain features in each case suggest that perforation may not be secondary to increased intraluminal pressure from the enema, but that necrotic perforated bowel is uncovered as the intussusception is reduced. A review of the basis for recommendations about the height of the enema bag during attempted reduction suggests that these guidelines are largely arbitrary and lack scientific support. PMID- 1625129 TI - Short-bowel syndrome: a collective review. AB - Neonates can now be expected to survive with very short lengths of bowel because of advances in pediatric neonatal care and in parenteral and enteral nutrition. Most pediatric surgeons have only a few patients with this problem under their care, so individual experience is limited. This collective survey, carried out by postal questionnaires to pediatric surgeons in the British Association of Paediatric Surgeons in the United Kingdom with an interest in the gastrointestinal tract, documents current techniques of management, the complications encountered, and reviews the clinical and economic consequences of prolonged total parenteral nutrition. We conclude that within the limitations of resources and our understanding of prognosis, neonates, especially if less than 35 weeks' gestation, with remaining jejunoileal segment of greater than 20 cm with an intact ileocecal valve (ICV) or greater than 30 cm without an ICV, should be considered salvageable. PMID- 1625130 TI - Human amniotic membrane as an intestinal patch for neomucosal growth in the rabbit model. AB - This experiment was carried out as a preliminary study, an attempt to grow new intestinal mucosa on human amniotic membrane in the terminal ileum in 37 rabbits. After ketamin sulfate anesthesia at laparatomy, 5-cm ileal defects were patched with human amniotic membrane (5 x 2 cm). These patched intestines were investigated on the first postoperative day and the 2nd, 5th, 10th, and 20th weeks corresponding to 4, 5, 5, 10, and 10 rabbits, respectively. Only three rabbits died in the early postoperative period. There was no evidence of intestinal obstruction or dilatation with barium meal. Microscopically, the neomucosa consisted of a thin layer of columnar epithelial cells at 2 weeks with more maturity of the villi and less irregularity and branching by 20 weeks. All patches were covered with neomucosa commencing at 2 weeks and covering the whole patch area by 20 weeks. This technique's advantages are the large size and the ease of the availability of the human amniotic membrane for neonates at risk without jeopardizing the neonates tissues. It is hoped that this method might be considered when neonatal material is scarce. PMID- 1625131 TI - Patchy distribution of rejection changes in small intestinal transplantation. AB - The aim of this study is to determine the distribution of histological changes of rejection in small intestinal transplantation. Thirty-nine rats were randomized into two groups: group I (n = 15), syngeneic transplants and group II (n = 24), allogeneic transplants. Grafts were excised and examined on days 2, 4, and 8 after transplantation. All grafts of the syngeneic group showed normal mucosa by day 4. However, by this time, all grafts of the allogeneic group demonstrated rejection changes with a patchy distribution in the mucosa. Therefore, with a biopsy from the stoma site there is a risk of missing early rejection. PMID- 1625132 TI - Intraanal ultrasound: a new aid in the diagnosis of pelvic processes and their relation to the sphincter complex. AB - Intraanal ultrasound provides a very accurate structural analysis of the continence organ. In addition it proved to give excellent pictures of solid or fluid intrapelvic, particularly retrorectal, structures. It is superior to computed tomography and magnetic resonance imaging (requiring anesthesia), because the scanner is very close to the structures in question. This allows high scanner frequencies with resolutions of 0.9 mm and better. It is a quick method, avoiding radiation, and can be safely repeated as often as necessary. PMID- 1625133 TI - Comparison of saphenous versus jugular veins for central venous access in children with malignancy. AB - A retrospective analysis was carried out to compare the performance and complications of central catheters inserted into either the saphenous (27) or jugular (52) veins. The saphenous route may be preferred in certain circumstances including extensive mediastinal pathology, prior neck surgery, previous catheter(s), and cosmetic reasons. There was no difference in complications (local or systemic catheter-related infections, catheter occlusions, or venous thrombosis). The incidence of catheter removal due to complications was also not different between sites. Hence, the saphenous route can provide an additional portal of vascular access in selected patients. PMID- 1625134 TI - Therapeutic significance of surgery in advanced neuroblastoma: a report from the study group of Japan. AB - The role of surgery was evaluated in 19 stage III and 102 stage IV neuroblastoma patients, all of whom were treated with intensive induction chemotherapy by the Study Group of Japan between January 1985 and March 1990. For stage III neuroblastoma, surgical intervention at the primary site was performed in 18 of the 19 patients, 9 during and 9 after the first three cycles of A1 regimen, consisting of high-dose cyclophosphamide, vincristine, THP-adriamycin, and cis platinum. Gross complete resection of primary tumor and regional lymph nodes was feasible in 17 of the 19 patients (89%), and the survival rate for the 17 patients were 79%, 70%, and 70% at 2 years, 3 years, and 4 years, respectively. For stage IV, surgical intervention at the primary site was performed in 92 of the 102 patients (90%): 30 cases during the first 3 cycles of A1 chemotherapy and 62 cases after that, with gross complete resection accomplished in 81 of the 102 patients (79%). The 81 patients with gross complete resection achieved had a better prognosis than those 11 patients with partial resection (P less than .05). Overall survival rate was 62% at 2 years for 27 patients who underwent complete resection after 3 cycles of A1 when resolution of all metastases was obtained, whereas the survival was 52% at 2 years for 31 patients who similarly underwent complete resection but when evidence of persistent metastases was present. Patients in whom the ipsilateral kidney was preserved at surgery had an outcome superior to that of those with associated nephrectomy (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625135 TI - Characteristics and management of patients with fetal neuroblastoma. AB - At 35 weeks 6 days of gestational age, ultrasound evaluation of the fetal abdomen showed a mixed cystic mass in the superior pole of the left kidney. The mass was suspected to be an adrenal hemorrhage or neuroblastoma. The diagnosis was fetal neuroblastoma. Differential diagnosis enabled the fetal neuroblastoma to be distinguished from adrenal hemorrhage. The parameters of diagnosis of fetal neuroblastoma include no specific ultrasonographic pattern, lack of palpability, and no tumor markers. However, certain features do characterize fetal neuroblastoma, such as little metastases, complete resection at operation, and excellent prognosis. In cases of suspected neuroblastoma, a laparotomy performed as soon as possible is generally regarded as the best course of treatment. Nonetheless, biological analyses of the tumor may prove in the future to be necessary for determining whether or not laparotomy is the best treatment. PMID- 1625136 TI - Rapid development of an immunoblastic lymphoma and death in children following cadaveric renal transplantation. AB - We report on three children who underwent cadaveric renal transplantation and subsequently developed an immunoblastic lymphoma, leading to death in two patients. The development of the lymphoma occurred following a multi-drug immunosuppression regimen ending with monoclonal antilymphocyte (OKT3) treatment for biopsy-proven cellular and vascular acute rejection. These patients represent three of 11 children who received OKT3 treatment for rejection in the last 18 months at this institution. Following the diagnosis of lymphoma, all three patients were treated by transplant nephrectomy, cessation of immunosuppression, and administration of intravenous acyclovir. The first two patients died at 4 days and 4 weeks, respectively, after the definitive diagnosis was made with widespread metastatic disease. The remaining child is a short-term survivor (13 months), free of demonstrable malignancy. Multidrug regimens for immunosuppression have a profound effects on T cell function. These effects, when combined with a primary infection by the Epstein-Barr virus, are implicated in the rapid development of the lymphomas and are responsible for the death of these two children. PMID- 1625137 TI - Evaluation of factors contributing to mortality in pediatric renal transplant recipients. AB - From 1969 to 1985, 303 renal allografts (290 cadaveric) were placed in 215 pediatric recipients. A review of actuarial recipient and allograft survival 2 years posttransplant showed good results in patients over 6 years of age (greater than 90% for patients, about 70% for allografts) but less satisfactory results in younger patients (75% for patients, about 45% for allografts). Thirty-nine patients died. Loss of allograft function preceded death in 67% of cases and was due to rejection (61%), renal vascular thrombosis (35%), and recurrence of original disease (4%). On retrospective analysis, 13 deaths might have been preventable with current diagnostic and therapeutic modalities. Allograft dysfunction from thrombosis occurs at a higher frequency in the young child and may be confused with rejection. Treatment of rejection without biopsy, overagressive treatment of a chronically failing graft, and failure to withdraw immunosuppressive therapy in face of infection are poorly tolerated in the very young recipient and are prominent causes of preventable mortality. Transplant nephrectomy and repeated attempts at transplantation are poorly tolerated in very young patients. Patient survival is very dependent on the success of the initial allograft in children. PMID- 1625138 TI - Surgical management of duplex ureteroceles. AB - We reviewed the cases of 95 children with duplex ureteroceles treated in this department over an 18-year period. There were 101 ureteroceles (6 bilateral). Diagnosis and treatment were analyzed. Special attention was paid to newborns screened in utero. We always strove to preserve functional renal tissue whenever possible. In keeping with this goal, three surgical techniques were used: (1) upper pole heminephrectomy; (2) ureterocele excision, bladder neck reconstruction, and ureter reimplantation with or without cutaneous ureterostomy of the upper pole ureter; and (3) endoscopic ureterocele incision. Follow-up studies using x-ray and radionuclide imaging demonstrated satisfactory renal function in 86.6% of patients. These findings support a conservative approach to ureteroceles using endoscopic ureterocele incision as the primary treatment. Lower urinary tract reconstruction may be associated in cases involving urinary tract infection, obstruction or incontinence. Upper pole heminephrectomy should be performed only after functional evaluation following ureterocele incision or cutaneous ureterostomy. PMID- 1625139 TI - Ventriculoatrial shunt utilizing the azygos vein. AB - Long-term ventricular cerebrospinal fluid shunting can prove difficult in the neonatal population, particularly in those neonates who have had previous abdominal and vascular procedures. This article presents a technique of providing vascular access for ventriculoatrial shunting via the azygos vein for patients with limited vascular access and in whom ventriculoperitoneal shunting is not feasible. PMID- 1625140 TI - Esophageal tracheoplasty for congenital tracheal stenosis. AB - Two infants with congenital long tracheal stenosis underwent operation by means of an esophageal tracheoplasty. The first patient had previously undergone tracheal reconstruction using the pericardium. Although ventilation improved somewhat following this procedure, the pericardial patch suddenly ruptured 12 days after the operation, requiring an immediate esophageal tracheoplasty. The esophageal portion of the reconstructed trachea epithelialized 1 month later, with the lumen maintaining its proper size. However, the patient died 3 months after the second tracheoplasty. The cause of death was thought to be due to complications arising from prolonged high-pressure use of mechanical ventilation. He had been on a respirator for 6 months before the first tracheoplasty. The second patient has been doing well with no recurring respiratory problems for 25 months now. Her reconstructed trachea has adapted with her growth. This technique should be considered along with other forms of treatment for tracheal reconstruction because it is relatively simple and pliable. PMID- 1625141 TI - Insertion of a soft silastic nasogastric tube at operation for esophageal atresia: a new technical method. AB - A new and simple technical method for insertion of a soft silastic nasogastric tube into the stomach in neonates born with esophageal atresia is described. The technique is simple, easy to perform, and enables feeding the baby through this tube a day after the operation. Our method is based on the principle used in insertion of Broviac-Hickman catheters, namely the use of a "peel-away sheath" through which the silastic feeding tube is threaded. We have used this technique in five patients with esophageal atresia without any complication. PMID- 1625142 TI - The use of endotracheal tubes to assist in manipulation of esophageal strictures, in elongation of the esophagus in esophageal atresia, and in gastrojejunal feeding tube placement. AB - Because of the special qualities of a PVC endotracheal tube (smooth, soft, pliable but still with a patent lumen), it serves very well for the intubation of the esophagus or the duodenum through an established gastrostomy. In this article the use of endotracheal tubes in different manipulations of the esophagus and gastroduodenum is described. PMID- 1625144 TI - Renal infarction associated with an extraadrenal pheochromocytoma. AB - A patient with an abdominal extraadrenal pheochromocytoma showed computed tomography findings of renal infarction. Selective angiography of the affected kidney showed no evidence of arterial occlusion or emboli. We postulate that the renal infarcts were caused by reversible severe vasospasm associated with high systemic blood levels of norepinephrine and angiotensin II. PMID- 1625143 TI - Intestinal button implantation for obstipation and fecal impaction in children. AB - Chronic obstipation and fecal impaction in children can be difficult management problems for pediatricians. We describe a novel approach to the management of obstipation and fecal impaction: the implantation of the button gastrostomy device in the appendiceal stump or the terminal ileum. We report the procedure in two children. One child had pseudoobstruction syndrome complicated by recurrent obstipation; the other had cystic fibrosis complicated by recurrent obstruction from meconium ileus equivalent. Both children received a polyethylene glycol/electrolyte solution, with or without pancreatic enzymes, which was administered through the button. The children have remained essentially asymptomatic for at least 10 months. We believe that this is the first report of the use of a button gastrostomy device to successfully manage chronic obstipation and recurrent fecal impaction in children. PMID- 1625145 TI - Ovarian teratoma with gliomatosis peritonei. AB - Gliomatosis peritonei (GP) is a rare occurrence associated exclusively with ovarian teratoma (OT), in which numerous metastatic nodules composed mainly of mature glial tissue are studded on the peritoneum, omentum, and bowel wall. Two female patients (aged 5 years and 14 years) are reported. Various preoperative examinations confirmed a large abdominal teratoma with normal alpha-fetoprotein and beta-HCG. The OT was excised and partial omentectomy and incidental appendectomy were performed to remove as many metastatic nodules as possible. Pathological examinations including immunostains for glial fibrillary acidic protein showed predominantly mature glial tissue in the OT and in the metastatic nodules. An addition, chemotherapy was given to one of them, but both were well without recurrent diseases 17 months and 12 months postoperatively, respectively. The outcome of these two cases, in contrast to advanced malignancy in widespread intraperitoneal metastases of any other kind, supports the concept of benign nature of GP and a conservative surgical approach to this rare disorder. PMID- 1625146 TI - Recurrent peripheral arterial occlusion by leukemic cells sedimentation in acute promyelocytic leukemia. AB - A 10-year-old boy presenting with recurrent successive events of peripheral arterial occlusion in both legs, more prominent on the left side, was diagnosed as having acute promyelocytic leukemia. Histological examination of the occluding material showed that it was composed of leukemic blast cells. The boy underwent five operations. Each time the arterial flow was reestablished by removing cylindrical hollow white material obstructing the lumen. However, after the last operation, irreversible ischemia developed, necessitating an above-knee amputation. There was no evidence of disseminated intravascular coagulation. Three months later a right lumbar sympathectomy was performed for relief of causalgic-ischemic pains, with successful results. Preoperative angiography demonstrated irregular narrowing of the right iliac arteries and tibioperoneal trunk stenosis. PMID- 1625147 TI - Necrotizing fasciitis in two children with acute lymphoblastic leukemia. AB - Necrotizing fasciitis is a severe, soft tissue infection, and is an unusual condition in children. The cornerstone of therapy is prompt, aggressive surgical treatment. Despite vigorous treatment, mortality rates are high. We report the occurrence of necrotizing fasciitis in two children during the granulocytopenic phase of induction chemotherapy for acute lymphoblastic leukemia. The diagnosis and treatment of necrotizing fasciitis in these two children was made more difficult by their underlying disease and its chemotherapy. The successful treatment of their infections relied on a multimodality approach. Aggressive surgical debridement was the mainstay of therapy. Adjuvant therapy was vital to the successful outcomes and included meticulous wound care, intravenous hyperalimentation, appropriate antibiotics, and granulocyte transfusions. PMID- 1625148 TI - The natural history of periodontal disease in man: prevalence, severity, and extent of gingival recession. AB - This paper describes the occurrence and levels of gingival recession in 2 cohorts of individuals participating in parallel longitudinal studies in Norway (1969 1988) and Sri Lanka (1970-1990), covering the age range from 15 to 50 years. In the Norwegian cohort gingival recession had begun early in life. It occurred in greater than or equal to 60% of the 20 year-olds and was confined to the buccal surfaces. At 30, greater than or equal to 70% had recession, which still was found mainly on buccal surfaces. As the group approached 50 years of age, more than 90% had gingival recession; greater than or equal to 25% of the buccal surfaces were involved, greater than or equal to 15% of lingual, and 3 to 4% of the interproximal surfaces. In the Sri Lankan cohort greater than or equal to 30% exhibited gingival recession before the age of 20 years. By 30 years, 90% had recession on buccal, lingual, and interproximal surfaces; and at 40 years, 100% of the Sri Lankans had recession. As they approached 50 years, gingival recession occurred in greater than or equal to 70% of the buccal, greater than or equal to 50% of the lingual, and 40% of the interproximal surfaces. Based on the special features of the two cohorts, the working hypothesis is advanced that there is more than one type of gingival recession and probably several factors determining the initiation and development of these lesions. PMID- 1625149 TI - In vitro phagocytosis by crevicular phagocytes in various forms of periodontitis. AB - Phagocytes from the gingival crevice fluid (CF-cells) of 11 patients with localized juvenile and post-juvenile periodontitis (LJP/PJP), 14 with rapidly progressive periodontitis (RPP), 11 with adult periodontitis (AP), and 14 controls without periodontal disease were examined. Phagocytic activity in vitro was assessed. Crevicular washings were obtained from healthy sites of controls and diseased sites of patients after completion of the oral hygiene phase (professional and home care). The cells were carefully processed to avoid mechanical damage. The in vitro phagocytosis by uptake of opsonized C. albicans was performed in a moist chamber (30 minutes, 37 degrees C) and examined by light microscopy. CF-cells were differentiated on the basis of their morphological appearance. The majority of cells in crevicular washings were PMNs, some macrophages, and few lymphocytes. Phagocytic activity in patients with LJP/PJP and RPP was significantly decreased in comparison with that from AP and the control group. The decreased percentage of cells phagocytosing opsonized C. albicans was associated with the enhanced adherence of opsonized C. albicans. Moreover cell viability of CF-cells from LJP/PJP sites was significantly reduced. The data from the present study suggest that the in vitro phagocytosis of crevicular phagocytes in juvenile and rapidly progressive periodontitis lesions is diminished. PMID- 1625150 TI - Analysis of site specific periodontal bacteria sampling schemes. AB - A great deal of controversy has existed in the periodontal literature as to whether the site or the subject should be the unit of analysis. Using the site as the unit of analysis assumes that observations of sites within the same subject are independent and ignores between subject variation. The purpose of this report is to evaluate the influence that the unit of analysis has on estimating the number of necessary site specific bacterial samples from each subject. The number of bacterial samples per subject was defined as the number of samples that would insure a clinician at a 95% confidence level that, if the bacteria were present in a subject, it would be discovered. From two data sets in which 20 to 30 bacterial samples were taken from each subject and data generated from a simulation, appropriate within-subject sample size was determined. In one data set the presence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Bacteroides forsythus, and Prevotella intermedia was determined by indirect immunofluorescence. In the other data set the presence of A. actinomycetemcomitans, P. gingivalis, and P. intermedia was determined using DNA probes. Results of this study demonstrate that there is a large between subject variation in site specific bacterial prevalence, as indicated by an elevated intraclass correlation. Simulated data in this report demonstrated that the number of necessary bacterial samples per subject increased with increasing values of intraclass correlation. The number of necessary within subject samples also increased with decreasing prevalence rate. For A. actinomycetemcomitans, which had a low prevalence rate (0.11 to 0.18), the number of necessary samples per subject was very high (31 to 35).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625151 TI - Mitogenic, chemotactic, and synthetic responses of rat periodontal ligament fibroblastic cells to polypeptide growth factors in vitro. AB - The mitogenic, chemotactic, and synthetic responses of rat periodontal ligament (PDL) fibroblastic cells to epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), recombinant human platelet-derived growth factor (rhPDGF) AB, rhPDGF-BB, natural (n) PDGF-AB, and insulin-like growth factor-I (IGF-I) were examined in vitro using PDL cells obtained from the coagulum of healing tooth sockets. PDGFs and IGF-I have potent and comparable mitogenic effects on PDL fibroblastic cells. The maximum mitogenic effect of PDGFs was observed at the concentration of 10 ng/ml, whereas that of IGF-I was seen at concentrations higher than 100 ng/ml. In contrast, EGF induced moderate, and TGF-beta inhibitory mitogenic responses. The combination of rhPDGF-AB with either EGF or TGF-beta demonstrated comparable mitogenic potency, equivalent to the level of PDGF alone regardless of the mitogenic effect of other growth factors. The combination of rhPDGF-AB and IGF-I, however, showed a synergistic effect revealing the highest mitogenic effect among all individual growth factors as well as any combinations of the growth factors tested. Similarly, PDL fibroblastic cells demonstrated strong chemotactic responses to both IGF-I and PDGFs. The maximum effect was observed by IGF-I at concentrations higher than 10 ng/ml, followed by rhPDGF-BB at 0.1 ng/ml, rhPDGF-AB and nPDGF at concentrations ranging from 0.1 to 1 ng/ml. TGF-beta revealed no, and EGF slightly increased, chemotactic effects. IGF-I slightly enhanced the synthesis of total protein, whereas other factors had no significant effect. However, both rhPDGF-AB and TGF-beta stimulated collagen synthesis. On the other hand, IGF-I showed no effect on collagen synthesis, while EGF suppressed collagen synthesis. These findings suggest that rhPDGF-BB and IGF I stimulate proliferation and chemotaxis of PDL fibroblastic cells. In addition, the combination of these growth factors further increases the mitogenic effect. rhPDGF-AB also stimulates collagen synthesis by PDL fibroblastic cells. Thus, rhPDGF-BB and IGF-I may have important roles in promotion of PDL healing, and consequently, may be useful for clinical application in periodontal regenerative procedures. PMID- 1625152 TI - The effects of chlorhexidine digluconate on human fibroblasts in vitro. AB - The drug chlorhexidine has been widely utilized as a wound antiseptic and oral antimicrobial rinse. There have been numerous reports on its safety as an oral rinse, but its effects on wound healing have been contradictory. The present study utilized human fibroblasts derived from skin and oral tissues to test the effects of chlorhexidine on viability, growth, collagen gel contractions, and total protein synthesis. Cells were exposed for an hour to 0.005% and 0.002% chlorhexidine and for 30 seconds to 0.12% chlorhexidine. Our results indicate that a 0.002% concentration of the drug shows minimal cytotoxicity, but is able to suppress cell division almost completely. Collagen gel contraction, as a model of wound contraction, was also severely affected by all of the concentrations of chlorhexidine used. Total protein synthesis was suppressed by chlorhexidine in collagen gel culture. The data support the hypothesis that chlorhexidine is highly cytotoxic to cells in vitro, but various cell functions such as proliferation, collagen gel contraction, and protein synthesis are affected to different degrees by the drug. PMID- 1625153 TI - Clinical and light microscopic observations of gingivitis and early ligature induced periodontitis in the cynomolgus monkey. AB - Clinical and histological observations were made on gingivitis and ligature induced periodontitis in 4 adult female cynomolgus monkeys (Macaca fascicularis) to define the changes occurring in the early periodontitis lesion. Silk ligatures were tied around selected posterior teeth and replaced weekly for 4 weeks. The changes from gingivitis to periodontitis induced by ligation, and back to a state of clinical health after ligature removal, scaling and polishing, were characterized by Plaque Index, Gingival Index, probing pocket depth, attachment loss, and histologic evaluation. A mild, chronic marginal gingivitis was the normal finding in the gingiva of posterior teeth. The inflammatory infiltrate in the connective tissue contained primarily lymphocytes. Hygienic measures once a week reduced the amount of infiltrate and the epithelial proliferation, but did not eliminate it. Placement of silk ligatures rapidly changed the clinical picture to a moderate or severe gingivitis, which presented an almost bizarre response of sulcular and oral epithelium, with an increase in polymorphonuclear neutrophil infiltration. Within 2 weeks there was significant probing attachment loss. The clinical response on removal of ligatures and plaque was almost as rapid as the onset. The animal model is useful for manipulating variables in ways not possible in the study of human periodontitis. PMID- 1625154 TI - Early effects of periodontal therapy on the detection frequency of four putative periodontal pathogens in adults. AB - This study aimed to examine early posttreatment changes in the periodontal microflora. Paper point sampling and conventional bacterial cultivation were used to monitor the effects of surgical and non-surgical periodontal therapy on the detection frequency of Porphyromonas gingivalis, Prevotella intermedia, Actinobacillus actinomycetemcomitans, and Capnocytophaga species in deep periodontal pockets. Ten patients, 5 men and 5 women (mean age 44 years), with advanced periodontal disease were selected from the dental school patient population for the study. A total of 245 teeth in 10 defined areas of the dentition were treated by oral hygiene instruction followed by scaling and root planing alone (121 sites) or with surgical interventions (124 sites). Ninety sites, 47 surgical and 43 non-surgical, with initial pocket depth greater than or equal to 6 mm were sampled at baseline and 3 months after completion of therapy. Treatment by both procedures resulted in significant clinical improvements as assessed by all clinical parameters used. Baseline results may indicate that the level of P. gingivalis was reduced in the presence of P. intermedia, while A. actinomycetemcomitans seemed to be reduced in the presence of P. gingivalis and/or P. intermedia. Three months after therapy, the detection frequency of P. gingivalis was significantly reduced (P less than 0.05) in surgical and non surgical sites while the reduction for P. intermedia was significant only for surgical sites (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625155 TI - Gingival overgrowth among renal transplant recipients related to immunosuppressive medication and possible local background factors. AB - The aim of this study was to determine the occurrence of gingival overgrowth (GO) among renal transplant recipients and to analyze possible background factors causing GO among cyclosporine-treated (CsA) patients as compared with others receiving azathioprine (Aza). A total of 32 recipients, 22 treated with CsA and 10 with Aza (ages 22 to 68 years) participated. The examination included determination of renal function, whole blood CsA concentration, and periodontal status. The tooth surface data were analyzed in terms of the given background variables for GO in the whole patient sample by logistic regression analysis. The occurrence of GO was significantly higher in the CsA group as compared with the Aza group (P less than 0.03). The CsA responders had significantly more gingival units overgrown as compared with the Aza responders (P less than 0.005). There were no differences in age, sex, whole blood concentration of CsA, or duration of CsA medication between the responders and non-responders. Expressed as individual means, the gingival inflammation scores were significantly higher among the CsA responders than among the CsA non-responders (P less than 0.005). Analysis of the surface data showed that CsA had an independent major effect on GO. Furthermore, simultaneous gingival bleeding increased the risk of overgrowth (odds ratio = 2). The results show that CsA medication is a significant factor for GO and the risk of the occurrence of GO is further increased by simultaneous gingival inflammation. PMID- 1625156 TI - Guided tissue regeneration in the treatment of human facial recession. A 12-case report. AB - A guided tissue regeneration procedure was used to treat human buccal recessions, 3 to 7 mm deep, in 12 patients. No procedure for increasing the width of keratinized tissue was performed prior to treatment. A thick bipedicled flap was raised with a semilunar incision in the alveolar mucosa and a marginal incision was extended to the adjacent papilla. The root surface was made concave by curets and burs to create space for regeneration. The membrane was fixed to the cemento enamel junction and covered by the flap which consisted of the residual gingiva and of alveolar mucosa. The membranes were removed 4 weeks after placement. The patients were recalled 6 months after the reentry procedure. The average reduction in recession was 2.50 mm (P less than 0.01) and the average attachment gain was 2.84 (P less than 0.01). Pocket depth was slightly reduced (0.33 mm), although the degree of reduction was not of statistical significance. The width of keratinized tissue increased slightly (0.83 mm). These results demonstrate the possibility of treating human buccal recessions by means of a guided tissue regeneration procedure, with predictable recession reduction and attachment gain. A minimal amount of keratinized tissue was needed. PMID- 1625157 TI - Gingival lesions in lipoid proteinosis. AB - Lipoid proteinosis is a rare heritable disease of the skin and mucous membranes characterized by subepithelial deposits of hyaline material. The morbid factors include disfiguring papulo-nodular lesions particularly of exposed skin, hoarseness of voice due to vocal cord infiltration, nodular deformation of the eyelids, and board-like rigidity of the tongue. Infiltration of the gingiva is usually unreported, and when mentioned has been equivocally related to the overall disease process. This patient demonstrates striking ulceration and hypertrophy with histologic evidence of heavy deposition of amorphous material confirming a gingival component to the lipoid proteinosis entity. PMID- 1625158 TI - [Specific nutrition for the pregnant woman]. PMID- 1625159 TI - [Drug therapy for treatment of obstetrical pathology]. PMID- 1625160 TI - [Treatment of benign symptoms during pregnancy: advice for the community pharmacist]. PMID- 1625161 TI - [Infant sudden death]. PMID- 1625162 TI - [Maternal milk]. PMID- 1625163 TI - [The dietetic basis of infant nutrition]. PMID- 1625165 TI - [Milk substitution and diversification of nutrition]. PMID- 1625164 TI - [Infant digestive intolerance]. PMID- 1625166 TI - [Special milk substitutes]. PMID- 1625167 TI - [Trace elements and vitamins for pregnant women]. PMID- 1625168 TI - Protective effects of benidipine hydrochloride (KW-3049), a calcium antagonist, against experimental arterial calcinosis and endothelial dysfunction in rats. AB - Protective effects of benidipine hydrochloride (KW-3049) against arterial calcinosis and its possible mechanisms of action have been investigated. Arterial calcinosis was induced in rats by combined administration of vitamin D2 (1050000 IU/kg, s.c.) and nicotine (12.5 mg/kg, p.o., b.i.d.) for 6 successive days. Calcium antagonists, benidipine or nifedipine, were given orally twice a day during the same period. The aortic calcium content in vitamin D2 and nicotine treated (control) rats increased to about 25 times that in normal rats, accompanying an increase of serum calcium level. Benidipine (10 mg/kg, p.o., b.i.d.) reduced the aortic calcium content to about 18% of control rats without reducing the serum calcium level. Although the presence of aortic endothelial cells was observed under light microscopy in control rats, their surfaces were degenerated under scanning electron microscopy. Benidipine exerted a protective effect against these degenerative changes. Acetylcholine-induced endothelial dependent relaxation was attenuated in control rats, compared with that in normal rats. Benidipine significantly improved this attenuation of the relaxation. These results suggest that the anticalcinotic effect of benidipine is accompanied by its protective effect on endothelial cells. PMID- 1625169 TI - Selective analysis of mutual displacement effects at the primary binding sites of phenoxymethylpenicillin and cephalothin bindings to human serum albumin. AB - In order to analyze the mutual displacement effects on the protein binding of beta-lactam antibiotics, binding experiments with the human serum albumin (HSA) were performed for cephalothin (CET) and phenoxymethylpenicillin (PCV) by using the centrifugal ultrafiltration method. The numbers of primary and secondary binding sites, n1 and n2, and the affinity constants for the primary and secondary binding sites, K1 and K2 were determined for CET to be 1.00 +/- 0.06 (mean +/- S.D.) and 4.54 +/- 0.12 and 2.59 x 10(3) +/- 0.10 x 10(3) (M-1) and 2.59 x 10(2) +/- 0.16 x 10(2) (M-1), respectively, and for PCV to be 0.94 +/- 0.10 and 5.41 +/- 0.40 and 3.52 x 10(3) +/- 0.25 x 10(3) (M-1) and 4.07 x 10(2) +/- 0.54 x 10(2) (M-1), respectively. Using the predicted optimum unbound concentration of PCV, i.e., 4.6 x 10(-4) M, the displacement effect of PCV to the binding of CET at the primary site has been demonstrated, while no significant effect was observed at the secondary binding site. Moreover, a competitive displacement effect of CET was also demonstrated for the binding of PCV to HSA at the primary binding site, suggesting that CET and PCV bound to HSA at the same primary binding site. PMID- 1625170 TI - Relationship between lipophilicity and binding affinity with human serum albumin for penicillin and cephem antibiotics. AB - Relationship between structure and binding affinity to human serum albumin (HSA) has been studied for penicillin and cephem antibiotics. For penicillin analogs, a good correlation between the apparent affinity constants, Kapp, for HSA binding and the partition coefficient, Papp, determined in isobutyl alcohol-pH 7.4 phosphate buffer system was observed, indicating that the hydrophobic interaction of 6-substituent of penicillins with amino acid of HSA would play an important role for the binding. However, no correlation between the Kapp and Papp values was observed for cephem antibiotics. Mutual competitive displacement effects were demonstrated for the primary binding sites of cephalothin, cefazolin, cefotetan and cefatrizine, suggesting the presence of a common binding region in HSA among these cephem antibiotics examined. Significant differences were observed for the Kapp value among cephems having the same 3-substitute of N-methylthiotetrazole in the molecule, i.e., cefpiramide, cefotetan, cefoperazone, cefamandole, cefmenoxime, cefmetazole and cefbuperazone, suggesting that 7-substitute of cephem would play an important role for the binding with HSA. Moreover, comparing the binding affinity and the structure of 3-substitute for cephems, all of the analogs having a heterocycle bind strongly with HSA in spite of their low lipophilicity. These observations suggest that an interaction between heterocycle at the position 3 and HSA would contribute to an additional binding force for the binding of cephem antibiotics to HSA. PMID- 1625171 TI - A time for action. PMID- 1625172 TI - Children's participation in research: their right to consent. AB - This article discusses the ethical and legal considerations related to the inclusion of children in the research process. Specific attention is paid to situations in which customary guidelines are inappropriate. In addition, the results of a survey to determine the manner in which Institutional Review Boards are addressing these issues is presented with suggestions to assist nurse researchers in acquiring review board approvals. PMID- 1625173 TI - School-aged children's interpretation of their experience with acute surgical pain. AB - This study examined the intensity of pain children experience following surgical procedures, the relationship between analgesic administration patterns and perceived level of pain, and children's affective, cognitive, and sensory interpretation of their experiences with pain. The sample included 24 children between 7 and 11 years of age who were hospitalized after abdominal, orthopedic, or urologic surgery. Children rated the intensity of their pain on a visual analog scale three times on the day after surgery. A chart review examined analgesic administration. On the third day after surgery, children were interviewed about their experiences with pain. The findings provide insight into the content of children's fears and concerns when they have postoperative pain, and how they interpret their responses and the responses of others in the management of their pain experience. PMID- 1625175 TI - The short bowel syndrome: an update and a case study. AB - Infants with the short-bowel syndrome are living longer and are increasing in number due to new medical treatments and a larger number of survivals with very low birth weights. This article reviews the medical and nursing management of these infants. A case study of an infant with the short-bowel syndrome is presented with a detailed nursing care plan emphasizing the physical, emotional, and social care of these infants. PMID- 1625174 TI - Social competence of school-aged children with chronic illnesses. AB - This study examines social competence among 67 chronically ill children, aged 7 to 14 years, whose families participated in a grounded theory study of how families define and manage a child's chronic illness. Child Behavior Check List ratings (Achenbach & Edelbrock, 1983) by both fathers and mothers indicated a significantly greater risk for social competence difficulties among the chronically ill children as compared with the normative sample. Case vignettes, drawn from extensive interviews with family members, are used to show contrasting styles of family management and child coping and to suggest nursing interventions aimed at fostering social competence. PMID- 1625176 TI - Disease patterns in homeless children: a comparison with national data. AB - Although homeless children have increased in numbers as poverty has become feminized, minorities have become poorer, and low-income housing has become less accessible, little is known of their health problems. This study compared the health problems of a group of uninsured and homeless children visiting a free, nurse-managed, primary care clinic on Los Angeles' Skid Row with data from children's primary care visits to pediatricians and general and family physicians sampled in the National Ambulatory Medical Care Survey. Diagnoses were classified into the following health service categories: (a) acute, (b) communicable, and (c) chronic disease; (d) preventive and (e) injury care. Comparisons indicated that services to homeless children differed significantly from reimbursed services in the national sample in all categories except chronic disease. Demographic analysis indicated that homeless children were predominantly Hispanic Americans. When data from Hispanic children were examined, the pattern of differences between the homeless and National Ambulatory Medical Care Survey diagnostic categories persisted. This study shows the variations in nursing care which a group of high-risk, severely impoverished, uninsured children require. PMID- 1625177 TI - The family and chronic sorrow: role theory approach. AB - This article explores the presence of chronic sorrow in families of chronically ill children and applies role theory concepts in the understanding of this phenomenon. Research findings in the area of chronic sorrow, family adaptation, and role theory are used to formulate propositions specific to the application of role theory in the study of chronic sorrow. The clinical and research applicability for nurses working with families of chronically disabled children are discussed to assist in providing quality family-nursing care. PMID- 1625178 TI - Nursing services for children of families living in university housing. AB - A university-based ambulatory pediatric nursing clinic was developed for two purposes: (a) to provide clinical experiences for senior nursing students in pediatric ambulatory care, and (b) to deliver nursing services to families with children for whom no organized health service existed on campus. Topics covered in this article include a literature review, historical background, and description of services delivered. A brief case study depicts use of the nursing clinic by one family. PMID- 1625179 TI - Family foster care: a service under siege. PMID- 1625180 TI - Microcomputers in nursing practice: point of care clinical series software, Part II. PMID- 1625181 TI - Establishing an education program for non-English-speaking families. PMID- 1625182 TI - Effects of L-carnitine on carbon tetrachloride-induced changes in serum and liver lipids and acylcarnitines. AB - Effects of 0.5% L-carnitine-supplemented diet on carbon tetrachloride-induced alterations of hepatic and serum lipids were examined in male rats. Treatment with carbon tetrachloride significantly increased hepatic total lipids, triglycerides, and total carnitine, but these were not significantly altered by 0.5% L-carnitine supplementation. However, in plasma, supplementary carnitine significantly decreased nonesterified fatty acids and increased acylcarnitines. These suggest that carnitine may soften hepatic lipid load by releasing acylcarnitines in blood. PMID- 1625183 TI - Changes of 8-hydroxydeoxyguanosine levels in rat organ DNA during the aging process. AB - We investigated the accumulation of oxidative DNA damage during the aging process by using 8-hydroxydeoxyguanosine (8-OH-dG) as a marker. The 8-OH-dG is one of the oxidative DNA damage products and is supposed to be a critical factor in carcinogenesis involving oxygen radicals. The 8-OH-dG levels in the DNA of liver, kidney, brain, lung, and spleen were measured in male and female F344 rats 6- to 30-month-old. The 8-OH-dG levels in the liver and kidney DNA of male rats increased significantly with age, but did not change in brain, lung, and spleen. Similarly, the 8-OH-dG levels in the liver and kidney DNA of female rats significantly increased with age, while changes in the brain, lung, and spleen DNA were much smaller. These results indicate that the accumulation of oxidative DNA damage during the aging process varies among organs, with slight sex difference. PMID- 1625184 TI - Hepatomegaly is an early biomarker for hepatocarcinogenesis induced by peroxisome proliferators. AB - The relationship between hepatomegaly and the hepatocarcinogenesis associated with by peroxisome proliferators was examined. (1) Male F-344 rats were maintained on diets containing clofibrate, ciprofibrate, nafenopin, gemfibrozil, Wy-14, 643, di(2-ethylhexyl)phthalate (DEHP), or di(2-ethylhexyl)adipate (DEHA) at carcinogenic doses for 1 week. A close correlation between relative liver weights and hepatocarcinogenicity was observed (r = 0.910). (2) Administration of perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA), simfibrate, or DL 040, for which hepatocarcinogenicity is not known, resulted in hepatomegaly in all treated groups, this being especially marked in the PFOA case. Therefore, PFOA may have strong hepatocarcinogenic potential. (3) Administration of the antioxidants butylated hydroxyanisole (BHA) or vitamin E (VE) did not affect the hepatomegaly induced by DEHP. These results suggest that the hepatomegaly may be an early biomarker for prediction of the potential hepatocarcinogenicity of peroxisome proliferators. However, this requires further clarification in terms of its relation to the oxidative stress thought to be involved in peroxisome proliferator-induced hepatocarcinogenesis. PMID- 1625185 TI - Malignancy of proliferative pulmonary lesions in the Syrian hamster following inhalation of 239PuO2. AB - The malignancy of pulmonary lesions induced by inhaled 239PuO2 in the Syrian hamster was tested by transplantation in the hamster cheek pouch. Serving as negative and positive controls, 42 female hamsters were given either 0.9% sodium chloride (NaCl), ferric oxide suspended in NaCl (Fe2O3), or benzo(a)pyrene + Fe2O3 suspended in NaCl (BP), by intratracheal instillation. One hundred female hamsters were given a single, nose-only inhalation exposure to high-fired 239PuO2 (initial lung burden, 2.4 kBq). At intervals from 160 to 425 days after Pu inhalation or instillation, ten 1-mm3 tissue cubes were removed from the lung of each hamster and transplanted into the cheek pouch of male hamsters, for a total of 1320 transplantations. None of the lung transplants from hamsters receiving 239PuO2, NaCl, or Fe2O3 grew in recipient cheek pouches, but 14% of transplants from BP hamsters grew rapidly in the cheek pouch. Lung carcinomas were histologically identified only in BP hamsters and BP transplants. It was concluded that proliferative pulmonary lesions induced by a-irradiation of the lung of hamsters were not malignant, and that the malignancy of lung lesions in the hamster induced by ionizing radiation should be evaluated by transplantation. PMID- 1625186 TI - Breast cancer and diet in Spain. AB - Breast cancer is the foremost cause of cancer death in women. A possible relationship has been suggested between breast cancer and cholesterol-rich diets, although no clear link has been established till now. This is an epidemiological study of the evolution of breast cancer mortality in Spain during the period 1977 to 1985, and it was made in relation to the principal dietary components of this country. The study period involved has made it necessary to take into account the corresponding changes in demographic structure; thus, standardization or specific fitting permitted comparisons. Global energy consumption in Spain is under 150 kcal per person per day for 50% of the population, and less than 180 kcal per person per day for 98% (range: 140 to 162) during the study period involved. Low correlation values were observed in relating mean breast cancer mortality rates for the 50 Spanish provinces to the dietary components studied. However, the most significant correlations relate mean mortality rate to total lipids, fiber, cereals, and Vitamin C intake. PMID- 1625187 TI - Digestive cancer in relation to diet in Spain. AB - Dietary factors are widely considered to be largely responsible for the different cancer incidences observed in different populations. In the present study we investigated the possible influence of dietary habits on the incidence of digestive cancer in the provinces of Spain. Data on specific mortality due to digestive cancer corresponding to the period 1975 to 1985 were obtained from the Instituto Nacional de Estadistica. Nutritional data on the different provinces were in turn gathered from the Instituto de Nutricion del Consejo Superior de Investigaciones Cientificas. The information was processed by the SPSS statistical software package. Lifestyle and socio-cultural factors are found to influence dietary risk factors in digestive cancer, particularly among women. The most significant correlations with the different cancers studied corresponded to total energy intake (responsible for 27.4% of variance), animal fats, and smoked fish and coffee. The latter is related to oral and esophageal cancer in particular (responsible for 15.4% of variance). Consumption of carrots and frozen vegetables is responsible for 6.5% of variance, vs. 4.4% of variance for alcoholic beverages, sugar, and Vitamin D. Differences are noted between both the sexes and their relationship to the different cancers studied. PMID- 1625188 TI - Caffeine, theophylline, theobromine, and developmental growth of the mouse mammary gland. AB - The purpose of this study was to determine the comparative activities of three methylxanthines, i.e., 1,3,7-trimethylxanthine (caffeine), 1,3-dimethylxanthine (theophylline), and 3,7-dimethylxanthine (theobromine) on developmental growth of the mammary gland in ovarian-hormone treated, mature nulliparous female Balb/c mice. When caffeine or theophylline was administered daily (via drinking water, 500 mg/L) for 30 days to 17 beta-estradiol/progesterone-treated intact or ovariectomized mice, a significant (p less than 0.05) enhancement of hormone induced mammary gland lobulo-alveolar differentiation was observed. Caffeine or theophylline thus accelerated and/or intensified mammae lobulo-alveolar differentiation induced by the ovarian steroids. In contrast, theobromine (500 mg/L drinking water) did not significantly modify this developmental process. The stimulatory effect of caffeine and theophylline on mammae development was comparable quantitatively. In an effort to determine whether or not the stimulatory effect of caffeine or theophylline was directly on the mammary gland, small slow-release Elvax-40P pellets containing these methylxanthines were implanted directly into the mammary gland of mice concurrently treated with estrogen and progesterone. No significant stimulatory effect of caffeine or theophylline (or theobromine) was observed. Furthermore, the addition of methylxanthines (caffeine, 100 microM) to the culture media of whole mouse mammary glands (organ cultures) did not enhance lobulo-alveolar differentiation induced by mammotrophic hormones. Thus, while a consistent significant stimulatory effect of caffeine and theophylline on mammary lobulo/alveolar differentiation was observed when the methylxanthines were consumed orally (drinking water), no direct effect of these methylxanthines, when placed directly into the mammary gland or in culture media, on mammae development was observed. These data demonstrate that certain methylxanthines (e.g., caffeine and theophylline) but not others (e.g., theobromine) can significantly enhance mammotrophic hormone-induced mammary lobulo-alveolar differentiation in female Balb/c mice, an effect that appears not to be manifested via a direct action of the methylxanthines on the mammary gland. PMID- 1625189 TI - Development of tolerance to the analgesic activity of mu agonists after continuous infusion of morphine, meperidine or fentanyl in rats. AB - We investigated the role of intrinsic activity in the ability of mu-opioid agonists to produce tolerance to the analgesic effects of other mu agonists. Dose response curves were generated for each test drug before and 24 hr after 1 week s.c. agonist infusions, using a tail-flick procedure in male rats. Morphine tolerance was dose-dependent over a range of doses, 0.3 to 1.4 mg/kg/hr, infused for 7 days by osmotic pump; 0.8 mg/kg/hr (1/4 acute ED50/hr) shifted the morphine dose-response curve roughly 2-fold to the right. Morphine, fentanyl or meperidine were then infused for 1 week to induce tolerance; doses were based on equipotent acute s.c. doses (1/4 ED50/hr). Drugs tested for analgesic activity, using a cumulative dosing procedure, included morphine, fentanyl, meperidine, methadone, buprenorphine, etorphine and levorphanol. The relative potency (RP) was calculated for each animal by dividing the preinfusion analgesic ED50 by the postinfusion ED50. The potency of morphine, fentanyl, meperidine and levorphanol decreased after a 7-day infusion of 0.8 mg/kg/hr morphine (RP = 0.44-0.70), but the potency of etorphine (RP = 0.85) and methadone (RP = 0.78) were not significantly changed. Chronic infusions of 6.25 mg/kg/hr meperidine produced more tolerance than did morphine (RP = 0.11-0.51). No significant change in analgesic potency was seen in six of the seven test drugs after infusions of 0.01 mg/kg/hr fentanyl (RP = 0.81-1.27). Buprenorphine did not produce an analgesic response in rats that received infusions of any of the three mu agonists. The RP of drugs with low intrinsic activity was lower than the RP of high efficacy drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625190 TI - M2 muscarinic receptors inhibit isoproterenol-induced relaxation of canine airway smooth muscle. AB - Classification of muscarinic receptors in the central airways has revealed the coexistence of M2 and M3 muscarinic receptors in this tissue, with the M2 subtype being predominant. Although M3 muscarinic receptors have been linked to airway smooth muscle contraction, a functional role for the M2 subtype in this tissue has been unclear. In nonairway smooth muscle, stimulation of the M2 muscarinic receptor has been shown to be associated with inhibition of adenylyl cyclase. In the present study, characterization of muscarinic receptors in canine tracheal smooth muscle confirmed that the majority of these muscarinic receptors were of the M2 subtype (89 +/- 3%), with a minor population of M3 receptors (11 +/- 3%). In functional studies, both isoproterenol and forskolin cause a dose-dependent relaxation of precontracted airway smooth muscle. In tissues precontracted with methacholine, 11-([[2-(diethylamino)methyl]-1-piperidinyl]acetyl)5,11- dihydro-6H pyrido[2,3-6][1,4]benzodiazepine-6-one (AF-DX 116), a selective M2 antagonist, shifted dose-response curves to both isoproterenol and forskolin significantly to the left. In contrast, AF-DX 116 did not alter relaxation induced by the K+ channel opener BRL 38227. Furthermore, the ability of AF-DX 116 to enhance isoproterenol-induced relaxation appears to be limited to smooth muscle precontracted with muscarinic agonists because AF-DX 116 had no effect on isoproterenol dose-response curves in muscle strips precontracted with histamine. Hexahydrosiladifenidol (HHSiD), a selective antagonist for M3 receptors, did not shift the isoproterenol dose-response curve in muscle precontracted with methacholine. This study demonstrates that stimulation of M2 muscarinic receptors in canine airway smooth muscle plays an important role in functional antagonism by reducing the relaxation caused by agents such as isoproterenol and forskolin. PMID- 1625191 TI - Attenuation of amiodarone-induced lung fibrosis and phospholipidosis in hamsters by taurine and/or niacin treatment. AB - Therapeutic use of amiodarone (AD), an effective antiarrhythmic drug, is associated with serious pulmonary toxicity (e.g., fibrosis and phospholipidosis). In the present study, we tested if taurine and/or niacin, which prevent bleomycin induced lung toxicity, could prevent AD-induced lung toxicity in hamsters. AD alone significantly increased lung hydroxyproline (an index of fibrosis) and lung phospholipid (an index of phospholipidosis) levels to 154 and 133% of their control counterparts at 21 days, respectively. However, treatment of hamsters with taurine, niacin or taurine + niacin for 6 days before AD, and daily thereafter, significantly decreased subsequent AD-induced collagen accumulation. Similarly, phospholipid levels in niacin + AD and taurine + niacin + AD groups were decreased significantly compared to AD alone. We conclude that taurine and niacin administered p.o. either singly or in combination can significantly decrease AD-induced increases in lung collagen deposition and phospholipidosis and may, therefore, be potentially useful in reducing AD-induced pulmonary toxicity. PMID- 1625192 TI - In vitro pharmacology of L-158,809, a new highly potent and selective angiotensin II receptor antagonist. AB - L-158,809 interacted in a competitive manner with rabbit aortic angiotensin II (AII) receptors as determined by Scatchard analysis of the specific binding of [125I]Sar1Ile8-AII. The affinity of L-158,809 (IC50 = 0.3 nM) for AII receptors in this tissue was appreciably greater than that of other reported nonpeptide AII antagonists such as DuP-753 (IC50 = 54 nM) and EXP3174 (IC50 = 6 nM) and similar to the natural ligand, AII. L-158,809 also exhibited a high potency at AII receptors in several other tissues from different animal species (IC50 = 0.2-0.8 nM). In vitro functional assays utilizing AII-induced aldosterone release in rat adrenal cortical cells demonstrated further that L-158,809 acts as a competitive, high affinity antagonist of AII (pA2 = 10.5) and lacks agonist activity. L 158,809 also potently inhibited AII-induced inositol phosphate accumulation in vascular smooth muscle cells and contractile responses to AII in isolated blood vessels. The specificity of L-158,809 for AII receptors was demonstrated by its lack of activity (IC50 greater than 1 microM) in several other receptor binding assays and its inability to affect in vitro functional responses produced by other agonists. L-158,809 demonstrated a very high selectivity for the AT1 compared to the AT2 receptor subtype (AT2 IC50 greater than or equal to 10 microM). The high affinity and selectivity makes L-158,809 a valuable new tool for investigating the physiological and pharmacological actions of AII. PMID- 1625193 TI - In vivo pharmacology of L-158,809, a new highly potent and selective nonpeptide angiotensin II receptor antagonist. AB - L-158,809 (5,7-dimethyl-2-ethyl-3-[[2'-(1H-tetrazol-5yl)[1,1']-bi- phenyl-4-yl] methyl]-3H-imidazo[4,5-b]pyridine) is a potent, competitive and specific antagonist of AT1 subtype of angiotensin II (AII) receptors in in vitro radioligand binding and functional isolated tissue assays. The present study was carried out to characterize the in vivo pharmacology of this potent AII receptor antagonist. In conscious, normotensive and anesthetized pithed rats, L-158,809 inhibits AII (0.1 microgram/kg i.v.) elevations in blood pressure without altering pressor responses to methoxamine or arginine vasopressin. In conscious rats, the relative potencies (ED50) were 29 micrograms/kg i.v. and 23 micrograms/kg p.o. Duration of action with single i.v. or p.o. doses exceeded 6 hr in rats. In similar experiments using rhesus monkeys, the potencies of L 158,809 were 10 micrograms/kg i.v. and approximately 100 micrograms/kg p.o. In these rats and monkeys, L-158,809 was 10 to 100 times more potent than DuP-753 (losartan) and approximately 3 times more potent than the metabolite, EXP3174. AII-induced elevation of plasma aldosterone in rats was also inhibited by L 158,809. Unlike angiotensin converting enzyme inhibitors, L-158,809 did not potentiate the hypotensive responses to i.v. bradykinin. L-158,809 was antihypertensive in high renin hypertensive rats (aortic coarction) and volume depleted rhesus monkeys. The maximum hypotensive responses with acute doses of L 158,809 were equal to those with an angiotensin converting enzyme inhibitor in these renin-dependent animal models. From these in vivo data, L-158,809 is a selective AII receptor antagonist with high potency, good p.o. absorption, long duration and antihypertensive efficacy equal to angiotensin converting enzyme inhibition after single doses. PMID- 1625195 TI - Aminoglycoside-mediated calciuresis. AB - Gentamicin and calcium compete for binding to various tissues including renal tubular brush border. Moreover, gentamicin has calcium channel blocking properties in cardiac and vascular tissue. Calcium channel blockade in vitro by nifedipine or verapamil decreases calcium uptake by renal tubular epithelial cells. To determine the acute in vivo effects of gentamicin on renal calcium handling, we administered gentamicin 10 mg/kg as an i.v. bolus to F344 rats. Within 30 min of administration fractional excretion of calcium increased from a mean of 11 +/- 2% (S.E.M.) to 128 +/- 37%. There was no change in glomerular filtration rate, or urinary sodium, potassium or phosphate excretion. Maximum calciuria occurred immediately after administration, was dose-related and was correlated to preadministration urinary calcium. Urine calcium concentration was also correlated to urinary gentamicin concentration. Urinary calcium returned to base-line values within 90 min of bolus gentamicin administration, but remained elevated if a gentamicin infusion was continued. Parathyroidectomy and dietary calcium content did not affect gentamicin calciuria. Tobramycin, a less nephrotoxic aminoglycoside in the F344 rat, had calciuric effects similar to gentamicin. Verapamil, a calcium channel blocker which is largely excluded from the urine, and potassium dichromate, a nonaminoglycoside proximal tubular nephrotoxin, had no effect on urinary calcium. The mechanism of aminoglycoside calciuria is unclear, but may be related to competition between aminoglycosides and calcium for brush border binding, intraluminal calcium channel blockade by aminoglycosides or aminoglycoside inhibition of basolateral calcium ATPase or Na K ATPase. PMID- 1625194 TI - Protective effects of (2E)-3-[5-(2,3-dimethoxy-6-methyl-1,4- benzoquinoyl)]-2 nonyl-2-propenoic acid on endotoxin-mediated hepatitis in mice. AB - E3330 [(2E)-3-[5-(2,3-dimethoxy-6-methyl-1,4-benzoquinoyl)]-2-nonyl-2- propenoic acid] is a newly synthesized hepatoprotective quinone derivative. We examined the protective effects and possible mechanism of action of E3330 in three different endotoxin (lipopolysaccharide)-induced murine hepatitis models, in which tumor necrosis factor is suggested to play a critical role in the pathogenesis. One of these models was induced by i.v. injection of lipopolysaccharide in combination with D-galactosamine to mice. Oral pretreatment with E3330 improved the survival rate and attenuated the increase in plasma aminotransferase activities of the survivors. The other two models were induced by i.v. injection of lipopolysaccharide or a mixture of D-galactosamine and lipopolysaccharide in Propionibacterium acnes-primed mice. In both of these models, tumor necrosis factor was detected in the plasma within 3 hr of the injection. Oral pretreatment with E3330 attenuated the elevation of plasma tumor necrosis factor activity and protected mice from liver injury. Furthermore, E3330 inhibited the production of tumor necrosis factor from cultured Propionibacterium acnes-elicited murine peritoneal macrophages on stimulation with lipopolysaccharide in vitro. These findings suggest that the inhibition by E3330 of tumor necrosis factor production is the major mechanism of the protective effect of E3330 in these endotoxin mediated hepatitis models in mice. PMID- 1625196 TI - Role of aortic baroreceptors in ethanol-induced impairment of baroreflex control of heart rate in conscious rats. AB - This study investigated the relative contribution of aortic baroreceptors to the depressant effect of ethanol on arterial baroreceptor function. The acute hemodynamic effects of ethanol were studied in conscious freely moving aortic baroreceptor denervated (ABD) and sham-operated (SO) rats. ABD but not the sham operation caused immediate and significant (P less than .05) increases in mean arterial pressure and heart rate (HR) and an impairment of the baroreflex mediated control of HR (baroreflex sensitivity, BRS). Two to three days after ABD, these parameters, except the BRS, subsided to near-control levels. Both operations (ABD and sham) significantly reduced the daily water intake but the reduction was significantly greater in ABD rats. Intravenous administration of ethanol (0.1, 0.5 or 1.0 g/kg) to either SO or ABD rats produced short-lived dose related pressor and bradycardiac responses which correlated well with blood ethanol concentration. In SO rats, ethanol caused dose-related decreases in the slopes of the curves relating increments in mean arterial pressure induced by phenylephrine to corresponding bradycardiac responses; the higher dose significantly (P less than .05) reduced the slope from -2.03 +/- 0.14 to -1.28 +/ 0.18 beats/min/mm Hg, indicating an impairment of BRS. Conversely, in ABD rats, ethanol failed to influence the BRS; the slopes before and after ethanol (1 g/kg) were similar (-1.1 +/- 0.07 vs. -1.0 +/- 0.23 beats/min/mm Hg). The lack of ethanol effect in ABD rats cannot be accounted for by the assumption that aortic barodenervation depressed the baroreceptor reflex to its nadir or by a difference in concentration of blood ethanol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625197 TI - Influence of the adenosine receptor antagonist, CGS 15943A, on renal function after reconstruction of chronic renal artery stenosis in the dog. AB - Surgical reconstruction of chronic renal artery stenosis may correct the anatomical defect but not result in an initial improvement in function of the revascularized kidney. The functional and hemodynamic changes associated with surgical correction of the one-clip, two-kidney, canine model of renovascular hypertension were studied. In 14 dogs, a surgical clip was placed across the proximal renal artery and tightened to decrease perfusion pressure (RPP) and blood flow (RBF). One month later, measurements were obtained distal to the constriction, before and 30 min after vascular reconstruction. Surgical reconstruction was associated with a rise in RPP (86%, P less than .001), renal vascular resistance (47%, P less than .001) and RBF (22%, P less than .05). Creatinine clearance (CCr) remained unchanged, but a significant negative association existed between initial CCr and change in CCr. The role of adenosine in mediating these changes was examined using the selective receptor antagonist, CGS 15943A (CGS), or its vehicle. After vascular reconstruction, vehicle dogs sustained a marked increase in renal vascular resistance, with a 60 +/- 8 mm Hg rise in RPP, but only an 18% rise in RBF. In contrast, renal vascular resistance was unchanged in the CGS group, with a 56 +/- 7 mm Hg increase in RPP and a 69% increase in RBF (P less than .0001). CCr was not changed by either vascular reconstruction or CGS 15943A. Vascular reconstruction was associated with increases in urinary flow rate and sodium excretion in both groups, but this change was significantly greater in the CGS group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625198 TI - Chimeric M1/M2 muscarinic receptors: correlation of ligand selectivity and functional coupling with structural modifications. AB - Chimeric M1/M2 receptors were expressed in murine fibroblasts (B82) transfected with recombinant m1/m2 receptor genes. The binding affinities of a number of muscarinic antagonists and the agonist carbachol for these chimeric receptors were compared with the ligands' affinities for the M1 and M2 receptors expressed in the B82 cells. The tricyclic compounds, namely pirenzepine (PZ), 11-([2 [(diethylamino)methyl]-1-piperidinyl]acetyl)-5,11- dihydro-6H-pyrido-[2,3 6][1,4]benzodiazepine-6-one (AF-DX 116) and himbacine, shared a binding site between transmembrane domains VI and VII. However, the selective interaction of pirenzepine with M1 and AF-DX 116 and himbacine with M2 involved different structural regions. The high-affinity binding for 4-diphenylacetoxy-N- methylpiperidine and hexahydrosiladifenidol was confined to within loop o2 and transmembrane domains V and VI, which were clearly distinguishable from those of the tricyclic compounds. These results support the hypothesis that the ligands' stereochemical features are critical in their optimal alignment within the ligand binding pocket. The cytoplasmic i3 loop modulated the binding of carbachol such that receptors which contained the i3 domain from the M2 receptor exhibited a single high-affinity state, whereas those with the i3 domain from the M1 receptor had an additional low-affinity state for the agonist. The i3 regions are essential for the differential functional coupling of the M1 and M2 receptors to second messenger systems; however, additional upstream regions seem to be essential for a potent and efficacious activation of phospholipase C by the M1 receptor. This study provides new insight into the molecular basis of ligand selectivity. PMID- 1625200 TI - Norepinephrine amplifies angiotensin II-induced vasoconstriction in rabbit femoral artery. AB - Several reports have focused on the ability of angiotensin II to amplify vascular contractile responses to norepinephrine, but none have determined whether norepinephrine enhances angiotensin II-induced vasoconstriction. Measuring isometric contraction in isolated rabbit femoral artery rings, we have found that the angiotensin II-induced contractile response was amplified in the presence of a threshold contraction to norepinephrine, as manifested by a 2.9-fold leftward shift of the midpoint of the concentration-response curve with no change in the maximal response. This amplification was attenuated markedly by nifedipine (0.1 microM), a calcium channel antagonist, implicating calcium channel activation in the amplification phenomenon. Precontracting the smooth muscle with a threshold concentration of angiotensin II had no enhancing effect on further angiotensin responses, indicating that the norepinephrine-induced amplification was due to a specific action of norepinephrine, rather than to a precontraction itself. In experiments in which the angiotensin II response was diminished by the presence of the noncompetitive angiotensin II antagonist [Sar1 Ala8]angiotensin II (0.3 microM), norepinephrine affected the angiotensin II response primarily by increasing the maximal response attainable. Prazosin (0.1 microM) both blocked the norepinephrine threshold contraction and abolished completely the amplification. However, when the norepinephrine concentration was increased until a threshold contraction was elicited in the presence of a fixed concentration of prazosin, amplification of the angiotensin II response was restored. These results indicate that norepinephrine exerts its amplifying effect on angiotensin II via activation of alpha-1 adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625199 TI - Morphine potentiates transforming growth factor-beta release from human peripheral blood mononuclear cell cultures. AB - Opiates modulate a variety of immune responses by peripheral blood mononuclear cells (PBMC). In the present study, we investigated the effect of morphine on the release of several cytokines upon stimulation with mitogens. An interleukin (IL) 4-dependent HT-2 cell proliferation assay was used to quantify transforming growth factor-beta (TGF-beta). IL-6 and tumor necrosis factor-alpha (TNF-alpha) were measured by enzyme-linked immunosorbent assays. Morphine (1 pM and 10 nM) alone did not significantly modulate the release of TGF-beta, IL-6 or TNF-alpha. Upon stimulation with lipopolysaccharide and phytohemagglutinin, PBMC released more (P less than .01) TGF-beta, IL-6 and TNF-alpha than unstimulated PBMC. Exposure of PBMC to morphine (1 pM) for 24 hr substantially amplified (P less than .05) the release of TGF-beta in the following 24 hr incubation period. Morphine did not alter the release of immunodetectable IL-6 or TNF-alpha from stimulated cells. The amplifying effect of morphine on the release of TGF-beta was mediated through a naloxone-sensitive mechanism. Given the fact that TGF-beta has a potent immunosuppressive effect, morphine-potentiated release of TGF-beta from PBMC may be involved in the immunomodulatory activity ascribed to morphine. PMID- 1625201 TI - Toxicity of the 1-methyl-4-phenyl-2,3-dihydropyridinium and 1-methyl-4 phenylpyridinium species in primary cultures of mouse astrocytes. AB - The biochemical and toxic effects of the two monoamine oxidase-generated metabolites of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine were investigated using primary cultures of mouse astrocytes. After the addition of equimolar concentrations (25 microM) of these metabolites, namely 1-methyl-4-phenyl-2,3 dihydropyridinium (MPDP+) ion or 1-methyl-4-phenylpyridinium (MPP+) ion, similar levels of MPP+ accumulated within the astrocytes. Both MPDP+ and MPP+ caused cytotoxicity which was preceded by increased glucose utilization and lactate accumulation. The metabolites were equipotent in producing a rapid decrease in cellular ATP which correlated well with the intracellular accumulation of MPP+ and the loss of cell viability. When astrocytes were incubated in glucose-free medium, both ATP depletion and loss of viability occurred more rapidly. Formation of MPP+ from MPDP+ was not affected by the presence of astrocytes, because MPP+ concentrations increased over time at the same rate regardless of the presence or absence of cells. In contrast to pretreatment of cells with monoamine oxidase inhibitors before addition of MPTP, pretreatment of astrocytes with deprenyl and clorgyline had no effect on intracellular levels of MPP+ after exposure to MPDP+ or MPP+ and did not protect against ATP depletion or cytotoxicity. These results indicate that 1) MPP+ and MPDP+ cause similar metabolic changes leading to cell death probably via ATP depletion; (2) intracellular levels of MPP+ are directly correlated to cytotoxicity; and (3) MPDP+ toxicity is also correlated to intracellular MPP+ accumulation, further confirming that MPP+ rather than MPDP+ is responsible for cell damage. PMID- 1625202 TI - Effects of xylamine on vascular neuroeffector transmission. AB - The effect of xylamine on sympathetic neuroeffector transmission in rabbit isolated blood vessels was examined. Xylamine (10(-8) to 10(-6) M) caused a slowly progressing inhibition of the contractions of pulmonary artery evoked by electrical field stimulation. The inhibition was irreversible. Cocaine (3 x 10( 5) M) prevented the inhibitory action of xylamine (10(-7) M), but it did not reverse the inhibition caused by xylamine (10(-6) M). Xylamine (10(-7) to 3 x 10( 5) M) reduced the accumulation of [3H]norepinephrine (NE) (10(-8) M). In the presence of desipramine (10(-6) M), xylamine (10(-7) to 3 x 10(-5) M) and corticosterone (10(-6) to 10(-4)) reduced the 3H-accumulation. Xylamine (10(-7) to 10(-5) M) reduced the tissue NE content by up to 50%. Xylamine (10(-7) to 10( 6) M) antagonized in a noncompetitive manner the contractions of aorta evoked by NE (10(-9) to 3 x 10(-5) M), histamine (10(-6) to 3 x 10(-4) M) and 5 hydroxytryptamine (10(-8) to 3 x 10(-4) M). In the case of NE, the antagonism was more marked in the presence of either cocaine (3 x 10(-5) M) plus corticosterone (4 x 10(-5) M) or corticosterone (4 x 10(-5) M). In the presence of xylamine (10( 7) to 10(-6) M), cumulative addition of near maximally effective concentrations of NE, 5-hydroxytryptamine and histamine caused a progressive and complete relaxation of aorta. Xylamine (10(-7) to 10(-5) M) did not alter the contractions of aorta evoked by potassium (17-55 mM). The results support the contention that xylamine is an inhibitor of neuronal and extraneuronal uptake, an adrenergic neurone blocking agent and a noncompetitive antagonist of alpha-1 adrenoceptors, histamine and 5-hydroxytryptamine2 receptors. Xylamine is not a direct acting vasodilator on smooth muscle. PMID- 1625203 TI - Endothelin-3 effects on renal function and prostanoid release in the rat isolated kidney. AB - The direct effects of rat endothelin (ET-3) on renal function and prostanoid levels were examined in the isolated, oncotically perfused kidney of the rat. ET 3 at 0.75 and 2.0 ng/ml produced sustained increases in perfusion pressure of 46 and 83 mm Hg, respectively, as compared with control kidneys. Glomerular filtration rate was significantly higher than control after additions of ET-3 as was the absolute and fractional excretion of water and electrolytes. ET-3 increased perfusate 6-keto-prostaglandin (PG)F1 alpha (breakdown product of PGI2) levels and stimulated greater urinary excretion of PGE2 and PGF2 alpha than 6 keto-PGF1 alpha. ET-3 did not affect urinary excretion or perfusate levels of thromboxane B2. Time-dependent increases in renin release were suppressed by ET 3. Indomethacin (10 microM) prevented ET-3-induced increases in urinary and perfusate prostanoids; however, renal vasoconstrictor and excretory responses were the same in the presence or absence of indomethacin. These results indicate that ET-3 acts directly on the perfused rat kidney to increase the release of prostanoids from the vascular and urinary compartments. A modulatory influence of prostaglandins on the acute renal hemodynamic and excretory effects of ET-3 was not observed under these conditions. PMID- 1625204 TI - Effects of cocaine alone and in combination with bromocriptine in human cocaine abusers. AB - This study was conducted to determine whether the acute administration of bromocriptine, a dopamine agonist, modulates the acute pharmacologic effects of i.v. cocaine in humans. Eight current users of i.v. cocaine who were not seeking treatment for their cocaine abuse completed the study while they were inpatients on a research unit. Twelve drug conditions were tested in all subjects in randomized order under double-blind, double-dummy conditions and included cocaine (0, 12.5, 25 and 50 mg, i.v.) in combination with bromocriptine (0, 1.2 and 2.5 mg given orally 2 hr before the cocaine injection). Physiologic and subject- and observer-rated responses were measured. Cocaine alone significantly increased pupil diameter, heart rate and blood pressure, and ratings of drug effect, good effects, liking and rush. Bromocriptine alone significantly increased pupil diameter and heart rate, decreased blood pressure and had only minor effects on subjective measures. There were significant cocaine/bromocriptine interactions on diastolic and mean arterial blood pressure, with combinations producing significantly smaller increases compared to cocaine alone, and on heart rate, with combinations producing significantly larger increases compared to cocaine alone. The physiologic and subjective effects of cocaine were not modified by pretreatment with bromocriptine in any other way that might indicate either a therapeutic benefit or a safety concern. However, bromocriptine alone produced undesirable effects (fainting) that should be considered before administration to outpatient cocaine abusers. Any possible therapeutic benefits of acute administration of bromocriptine in cocaine abuse are not likely to be due directly to modulation of the acute effects of cocaine. PMID- 1625205 TI - Modulation by certain conserved aspartate residues of the allosteric interaction of gallamine at the m1 muscarinic receptor. AB - Muscarinic acetylcholine receptors belong to a superfamily of G-protein coupled receptors and contain within their structure several conserved aspartate residues. These residues have been implicated to play important roles in the interaction of agonists and their competitive antagonists with the receptor. In the present work, we investigated whether the same residues might also serve as important contact points for allosteric antagonists of muscarinic receptors, because the majority of these compounds are cationic in nature, or if such residues are involved in modification of receptor conformation by these antagonists. Gallamine was used as a prototype for these antagonists. Site directed mutagenesis of the m1 muscarinic receptor subtype was utilized to define some of the molecular determinants involved in cooperative allosteric interactions. We report that substitution of the aspartate residue at position 71, but not at positions 99 and 122 with asparagine, affected the affinity of gallamine for the unliganded m1 receptor. A similar substitution at positions 71 and 99 decreased the magnitude of its cooperative effects on the binding of [3H]N methylscopolamine. Our data suggest that these residues are implicated in cooperative interactions. At present, however, we cannot discount a more pivotal role of other residues on the receptor sequence in allosteric interactions. The data also support the notion that different molecular entities are required for the binding of allosteric antagonists as compared to the interaction of agonists and competitive antagonists at the receptor. PMID- 1625206 TI - Selective effects of cocaine on regional cerebral blood flow in the rat. AB - Cocaine is a potent central nervous system (CNS) stimulant whose primary mechanism of action is reuptake inhibition of the monoamines at presynaptic transporter sites. Drug-induced stereotypic motor effects may be due to actions within the dorsal striatum and associated structures while reinforcing properties have been attributed to action in the ventral striatal terminal fields of the mesolimbic system. Recent metabolic mapping studies have revealed activation of a limited number of CNS structures. However, because of the pharmacokinetic properties of cocaine, brief duration of action and complex behavioral actions, regional cerebral blood flow (rCBF), a rapid marker of neuronal activity, was used to identify structures involved in different temporal aspects of its pharmacologic profile. Conscious rats were injected i.v. with either 0, 0.1, 0.5, 0.75, 1.0 or 5.0 mg/kg cocaine, 1 min before administration of [14C]iodoantipyrene. A dose-related increase in rCBF was seen in specific terminal fields of the mesolimbic system such as the basolateral and corticomedial nuclei of the amygdala, ventral pallidum, olfactory tubercle and medial prefrontal cortex. Additional structures became activated at successively higher doses, including the nucleus accumbens and ventral pallidum. Biphasic responses were seen in several structures manifest as increased blood flow at 0.1 mg/kg and a decrease or no effect at the mid doses only to increase again after the two highest doses. Thus, rCBF appears to be a sensitive measure of the neuronal effects of cocaine and, as a brief temporal marker of neuronal activity, has identified activation of several novel CNS structures. PMID- 1625207 TI - Common mechanisms underlying the proconflict effects of corticotropin-releasing factor, a benzodiazepine inverse agonist and electric foot-shock. AB - The effects of corticotropin-releasing factor (CRF), a benzodiazepine inverse agonist (methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; DMCM) and electric foot-shock on rat conflict behavior were characterized and compared. Rats were trained to lever press under a multiple fixed-ratio schedule (FR 20) of food reinforcement in which responses during the first component were not punished, and the first response of each FR during the second component produced electric shock of an intensity sufficient to suppress responding by 10% to 15%. Intracerebroventricular injection of CRF (0.1-5.6 micrograms) caused a dose dependent decrease in the rate of responding in both components of the schedule. However, CRF was more potent in decreasing rates of punished responding (proconflict effect). DMCM (10-100 micrograms; i.c.v.) also decreased rates of punished and nonpunished responding and was more potent during the punishment component. The suppression of punished and nonpunished responding by CRF and DMCM was mimicked by increasing the shock intensity (delta = 0.1 to 0.6 mA) during the punishment component. To determine whether CRF, DMCM and electric shock shared common mechanisms for these effects, rats were pretreated with i.c.v. injections of either a CRF antagonist (alpha helical CRF9-41, 50 micrograms), a benzodiazepine agonist (chlordiazepoxide, 10 micrograms) or a benzodiazepine antagonist (flumazenil, 10 micrograms) before the administration of equieffective doses of CRF or DMCM or an increase in shock intensity. Chlordiazepoxide attenuated the effects of all three stimuli. Flumazenil antagonized DMCM and CRF, but not shock, implicating a pharmacologic interaction between CRF and benzodiazepine systems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625209 TI - Electrophysiologic actions of clofilium and lidocaine in ischemically injured canine epicardium. AB - The electrophysiologic actions of the Class III antiarrhythmic drug, clofilium, and the Class IB antiarrhythmic drug, lidocaine, were examined in ischemically injured canine epicardium, 4 days after coronary artery occlusion. Experiments were performed utilizing 1) composite electrode recordings from the intact heart in the anesthetized dog and 2) intracellular and extracellular recordings from superfused canine epicardium. In intact hearts, both clofilium (2 mg/kg i.v.) and lidocaine (6 mg/kg i.v.) increased refractoriness (188 +/- 16 to 331 +/- 39 and 288 +/- 18 msec, respectively, P less than .01), and produced tachycardia dependent conduction disorders in ischemically injured epicardium. For both drugs, slowing the sinus heart rate with vagus nerve stimulation (32 +/- 6/min) returned activation delays to predrug values. Unlike lidocaine, clofilium failed to increase maximal activation delays in ischemically injured epicardium preceding conduction block (116 +/- 14 msec vs. 71 +/- 7 msec and 147 +/- 16 msec for clofilium and lidocaine, respectively, P less than .01 for both drugs). In superfused epicardium, both clofilium (3 x 10(-7) M) and lidocaine (4 mg/l) prolonged refractoriness in ischemically injured epicardium (175 +/- 16 predrug vs. 273 +/- 33 msec, P less than .01) and (181 +/- 3 predrug vs. 216 +/- 10 msec, P less than .01), respectively, whereas only lidocaine reduced Vmax and prolonged local conduction times in the same tissue. The results demonstrate that 1) lidocaine increases refractoriness in ischemically injured tissue via a decrease in Vmax and conduction velocity and 2) clofilium increases refractoriness in ischemically injured tissue without altering action potential duration, Vmax or conduction velocity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625208 TI - Further studies on the modulation of regional brain neurotensin concentrations by antipsychotic drugs: focus on haloperidol and BMY 14802. AB - Acute and chronic treatment with the antipsychotic drug haloperidol or the potential antipsychotic BMY 14802 produce increases in regional neurotensin concentrations which are similar with respect to regional specificity (nucleus accumbens and caudate), time course, magnitude of increase and precedence by an increase in proneurotensin mRNA. The present study characterizes further the effects of haloperidol and BMY 14802 on regional brain neurotensin concentrations and compares certain of their effects to those of sulpiride. Neurotensin concentrations in discrete brain regions of adult, male, Sprague-Dawley rats were determined by radioimmunoassay. Both acute and chronic treatment with BMY 14802 produced significant decreases in the concentration of neurotensin in the frontal cortex. When administered concomitantly, low doses of haloperidol and BMY 14802 produced additive increases in neurotensin content in the nucleus accumbens and caudate. Increases in neurotensin content resulting from concomitant treatment, or with doses which produce maximal effects individually, were not greater than those produced by either drug alone. Concomitant administration of SCH 23390 and sulpiride attenuated the neurotensin increases observed after treatment with sulpiride. Increases in neurotensin concentrations produced by haloperidol and BMY 14802 were not antagonized by SCH 23390. These findings support the hypothesis that haloperidol and BMY 14802 modulate regional neurotensin concentrations through a common or similar mechanism which is distinct from that of sulpiride. PMID- 1625210 TI - Endothelin-1 stimulates contraction and ion transport in the rat colon: different mechanisms of action. AB - Endothelin-like immunoreactivity has been detected in all regions of the rat gastrointestinal tract. In the present study, we studied the effect of endothelin 1 (ET-1) on muscle contraction and ion transport in the rat colon. Isometric tension was recorded in colonic muscle strips oriented along their longitudinal axis. The effect of ET-1 on ion transport was investigated by assessing changes in short-circuit current in segments of muscle-stripped rat colon in Ussing chambers. ET-1 induced concentration-dependent contraction of the colon (EC50, 3 nM). The concentration-response curve to ET-1 was not modified by the neuronal blocker tetrodotoxin (0.1 microM) or by atropine (1 microM). Pretreatment of colon muscle strips with the calcium channel blockers diltiazem (0.1 microM) or nicardipine (1 microM) had no effect on the contractile response to ET-1. Furthermore, the response was not affected by removal of extracellular calcium. In the ion transport studies, serosal addition of ET-1 produced a transient, bumetanide (chloride secretion inhibitor) -sensitive, increase in transepithelial short-circuit current. The maximal increase was 107 +/- 13 microA/sq. cm, with an EC50 of 2.5 nM. The increase in short-circuit current evoked by ET-1 was not significantly affected by 1 microM atropine, but was reduced by 50% (P less than .05) by 1 microM tetrodotoxin, or removal of extracellular calcium. We conclude that ET-1 stimulates smooth muscle directly, whereas its effect on epithelial chloride secretion is mediated in part via the enteric nerves. Moreover, the effect of ET-1 in these two systems can be differentiated on the basis of sensitivity to extracellular calcium. PMID- 1625211 TI - P-450-dependent arachidonic acid metabolism in rabbit olfactory microsomes. AB - Microsomes isolated from rabbit olfactory epithelium catalyzed the conversion of arachidonic acid to several metabolites at a rate of 692 +/- 106 pmol/min/nmol P 450. The major metabolite was the omega-hydroxylated metabolite, 20 hydroxyeicosatetraenoic acid, accounting for 57% of the total metabolite produced. A putative omega-1 hydroxylated metabolite was also formed to a lesser extent. Epoxyeicosatrienoic acids were not detected with microsomal incubations, although metabolites corresponding to the dihydroxyeicosatrienoic acids were observed and represented about 20% of the total metabolite produced. The metabolism of arachidonic acid was also studied in a reconstituted system with six purified P-450 isoforms that are known to be expressed in rabbit olfactory mucosa. These included P-450NMa, P-450 2G1 (NMb), P-450 1A2, P-450 2B4, P-450 2E1, P-450 3A6 and a partially purified preparation of P-450 4A isoforms. The P 450 4A forms were the only enzymes to produce significant amounts of the omega hydroxylated metabolite of arachidonic acid. The other isoforms were either inactive (P-450NMa and P-450 3A6) or produced metabolites other than the 20 hydroxyeicosatetraenoic acid and, thus, cannot account for the majority of the miscrosomal metabolism of arachidonic acid. Immunoblot analysis with goat anti rat P-450 4A1 identified one major and a second minor protein of the P-450 4A gene family in olfactory microsomes. The same antibody identified two proteins in rabbit renal tissue that were significantly induced by pretreatment with clofibric acid and were present in a partially purified preparation of P-450 4A from rabbit renal cortex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625212 TI - Pharmacokinetic and pharmacodynamic comparisons between human granulocyte colony stimulating factor purified from human bladder carcinoma cell line 5637 culture medium and recombinant human granulocyte colony-stimulating factor produced in Escherichia coli. AB - The pharmacokinetics and biological activities of recombinant human granulocyte colony-stimulating factor (hG-CSF) produced in Escherichia coli were compared with those of hG-CSF purified from human bladder carcinoma cell line 5637 culture medium (5637-hG-CSF). Recombinant hG-CSF was biologically active in a bone marrow cell proliferation assay in vitro, with a dose-response curve similar to that of 5637-hG-CSF. The effects of 5637- and recombinant hG-CSF administered via i.v. injection to rats showed similar response patterns of neutrophil counts in peripheral blood. From these results, it is concluded that the O-linked sugar chain of hG-CSF does not contribute to the in vitro and in vivo biological activities. The pharmacokinetics of both forms of hG-CSF in rats were investigated using a sandwich enzyme-linked immunosorbent assay. After i.v. administration, the serum concentration-time curves of 5637- and recombinant hG CSF declined biexponentially. Total body clearance and steady-state volume of distribution of 5637-hG-CSF were smaller than those for the recombinant form. After s.c. administration, a lower peak serum level, smaller AUC, and lower bioavailability of 5637-hG-CSF were observed compared to recombinant hG-CSF. PMID- 1625213 TI - Metabolic effects of ritodrine in the fetal lamb. AB - Ritodrine infusion to fetal lambs causes numerous metabolic perturbations including hypoxemia. To investigate these changes further and to elucidate a mechanism for the development of hypoxemia, ritodrine was infused at rate of 2.6 micrograms/min into nine chronically catheterized fetal lambs for 8, 12 or 24 hr. Plasma levels of ritodrine (20.0 +/- 2.7 ng/ml) were within the range of those reported in human fetuses exposed to ritodrine tocolysis. Fetal arterial glucose levels nearly doubled (0.72 +/- 0.07 to 1.29 +/- 0.18 mM), whereas lactate levels rose more than 5-fold (1.54 +/- 0.11 to 8.67 +/- 1.12 mM), with the latter change leading to a decline in fetal arterial pH from 7.370 +/- 0.004 to 7.273 +/- 0.033. Fetal oxygen consumption (VO2) rose from 342 +/- 35 to 407 +/- 30 mumol/min.kg via an increase in fetal fractional O2 extraction (32.0 +/- 1.1 to 49.0 +/- 1.7%). The rise in fetal O2 extraction contributed to concurrent declines in fetal arterial PO2 (21.9 +/- 0.6 to 17.0 +/- 0.5 mm Hg) and O2 content (3.7 +/- 0.2 to 2.1 +/- 0.1 mM). Umbilical venous PO2 and O2 content also fell resulting in a decline in fetal O2 delivery (DO2) from 1115 +/- 97 to 838 +/ 68 mumol/min.kg. The rise in fetal VO2 was reflected by a similar rise uterine VO2 (not significant), with the latter being accompanied by a significant increase in uterine O2 extraction and decrease in uterine venous PO2 and O2 content, perhaps contributing to the fall in fetal DO2. In conclusion, fetal hypoxemia during the infusion of ritodrine results from an increase in fetal VO2 that is not compensated for by a similar increase in umbilical or uterine DO2. These metabolic effects may put the fetus at risk, particularly in situations in which fetal DO2 is already reduced, as may occur in compromised pregnancies. PMID- 1625214 TI - Effects of pH upon the inhibition by sulphonylurea drugs of ATP-sensitive K+ channels in cardiac muscle. AB - The effect of pH was tested upon the inhibition of ATP-sensitive K+ (KATP) channels caused by the sulphonylurea drugs tolbutamide and glibenclamide. KATP channels and currents (I-KATP) were activated with SR 44866 in ventricular myocytes isolated from guinea pig hearts. Modification of either external or internal pH had little effect upon the background K+ current (IK1). External pH had no consistent effects upon I-KATP. The application of NH4Cl inhibited I-KATP and its withdrawal caused a slight rebound activation. Compared with the results obtained at pHo 7.4, inhibition of I-KATP by the sulphonylurea drugs was enhanced at pHo 6.5 and reduced at pHo 8.4. The kinetics of the recovery of I-KATP was independent of pHo. Neither internal pH 6.5 nor NH4Cl had any effect upon sulphonylurea-induced inhibition of I-KATP. The dose-response curves for inhibition of I-KATP at different pHo's were found to coincide when plotted for the unionized concentrations of the drugs. It is concluded that it is the unionized forms of the sulphonylurea drugs which are responsible for closure of KATP channels in cardiac muscle. In consequence, extracellular acidification during ischemia will increase the effective concentration of glibenclamide and may be responsible for the cardiovascular disorders associated with this treatment in noninsulin-dependent diabetics. PMID- 1625215 TI - The effect of pulse repetition rate on the delay sensitivity of neurons in the auditory cortex of the FM bat, Myotis lucifugus. AB - 1. Echo delay is the primary cue used by echolocating bats to determine target range. During target-directed flight, the repetition rate of pulse emission increases systematically as range decreases. Thus, we examined the delay tuning of 120 neurons in the auditory cortex of the bat, Myotis lucifugus, as repetition rate was varied. 2. Delay sensitivity was exhibited in 77% of the neurons over different ranges of pulse repetition rates (PRRs). Delay tuning typically narrowed and eventually disappeared at higher PRRs. 3. Two major types of delay sensitive neurons were found: i) delay-tuned neurons (59%) had a single fixed best delay, while ii) tracking neurons (22%) changed their best delay with PRR. 4. PRRs from 1-100/s were represented by the population of delay-sensitive neurons, with the majority of neurons delay-sensitive at PRRs of at least 10 20/s. Thus, delay-dependent neurons in Myotis are most active during the search phase of echolocation. 5. Delay-sensitive neurons that also responded to single sounds were common. At PRRs where delay sensitivity was found, the responses to single sounds were reduced and the responses to pulse-echo pairs at particular delays were greater than the single-sound responses. In facilitated neurons (53%), the maximal delay-dependent response was always larger than the best single-sound responses, whereas in enhanced neurons (47%), these responses were comparable. The presence of neurons that respond maximally to single sounds at one PRR and to pulse-echo pairs with particular echo delays at other PRRs suggests that these neurons perform echo-ranging in conjunction with other biosonar functions during target pursuit. PMID- 1625216 TI - Circadian entrainment by feeding cycles in house sparrows, Passer domesticus. AB - We studied the potential zeitgeber qualities of periodic food availability on the circadian rhythms of locomotor and feeding activity of house sparrows. The birds were initially held in a LD-cycle of 12:12 h, with food restricted to the light phase. After transfer to constant dim light, the birds remained entrained by the restricted feeding schedule. Following an exposure to food ad libitum conditions, the rhythms could be resynchronized by the feeding cycle. Shortening of the zeitgeber period to 23.5 h resulted in the loss of entrainment in most birds, whereas a longer zeitgeber period of 25 h re-entrained the rhythms of most birds. Although these results prove that periodic food availability can act as a zeitgeber for the circadian rhythms of house sparrows, several features of our data indicate that restricted feeding is only a weak zeitgeber. The pattern of feeding activity prior to the daily time of food access shown under some experimental conditions suggests that anticipation is due to a positive phase angle difference of the birds' normal circadian system rather than being caused by a separate pacemaker. PMID- 1625217 TI - Appearance and maturation of voltage-dependent conductances in solitary spiking cells during retinal regeneration in the adult newt. AB - Electrical membrane properties of solitary spiking cells during newt (Cynops pyrrhogaster) retinal regeneration were studied with whole-cell patch-clamp methods in comparison with those in the normal retina. The membrane currents of normal spiking cells consisted of 5 components: inward Na+ and Ca++ currents and 3 outward K+ currents of tetraethylammonium (TEA)-sensitive, 4-aminopyridine (4 AP)-sensitive, and Ca(++)-activated varieties. The resting potential was about 40 mV. The activation voltage for Na+ and Ca++ currents was about -30 and -17 mV, respectively. The maximum Na+ and Ca++ currents were about 1057 and 179 pA, respectively. In regenerating retinae after 19-20 days of surgery, solitary cells with depigmented cytoplasm showed slow-rising action potentials of long duration. The ionic dependence of this activity displayed two voltage-dependent components: slow inward Na+ and TEA-sensitive outward K+ currents. The maximum inward current (about 156 pA) was much smaller than that of the control. There was no indication of an inward Ca++ current. During subsequent regeneration, the inward Ca++ current appeared in most spiking cells, and the magnitude of the inward Na+, Ca++, and outward K+ currents all increased. By 30 days of regeneration, the electrical activities of spiking cells became identical to those in the normal retina. No significant difference in the resting potential and the activation voltage for Na+ and Ca++ currents was found during the regenerating period examined. PMID- 1625218 TI - Calcium is necessary for light excitation in barnacle photoreceptors. AB - Illumination of barnacle (Balanus amphitrite) photoreceptors is known to increase the membrane permeability to sodium and Ca2+ ions resulting in a depolarizing receptor potential. In this report, we show that lanthanum (La3+), a known inhibitor of Ca-binding proteins, reversibly eliminates the receptor potential of barnacle photoreceptors when applied to the extracellular space. Similar reversible elimination of the light response was obtained by removing extracellular Ca2+ by application of the calcium chelating agent EGTA. Iontophoretic injection of Ca2+, but not K+ into the cells protected both the transient and the steady-state phases of the receptor potential from elimination by EGTA while only the transient phase was protected in the presence of La3+. The EGTA experiments suggest that internal Ca2+ is necessary for light excitation of barnacle photoreceptors while the La3+ experiments suggest that La(3+)-sensitive inward current is necessary to maintain excitation during prolonged light. PMID- 1625219 TI - Multiple gate control of the descending statocyst-motor pathway in the crayfish Procambarus clarkii Girard. AB - 1. Synaptic responses of uropod motoneurons and interneurons to magnetic field stimulation of the statocyst were studied in a whole animal preparation using intracellular recording and staining techniques to characterize the descending statocyst pathways controlling uropod steering behavior. 2. When the animal was engaged in abdominal postural movement, all uropod motoneurons received sustained excitatory input. Motoneurons which were to be activated during steering behavior showed excitatory responses to the stimulus superimposed on the sustained excitation. In the resting state, they showed weaker responses or no visible responses to the same stimulation. 3. Motoneurons to be suppressed during steering showed inhibitory responses to the stimulus only during abdominal movement. These included both active inhibition as well as disfacilitatory suppression of excitatory input to the motoneurons. 4. Premotor nonspiking interneurons, like motoneurons, showed greater responses to the stimulus during abdominal movement than at rest. Unlike motoneurons, however, they did not always receive sustained input during abdominal movement. 5. Descending axons which responded to statocyst stimulation independent of abdominal movement were found in the 4th and 5th abdominal ganglia. Other axons showed greater responses during abdominal movement than at rest. 6. A number of intersegmental descending interneurons with cell bodies and dendrites in the 4th or 5th ganglion were found to receive excitatory inputs from both the statocyst and the motor system controlling abdominal posture. These responses were found to summate with each other to generate spikes. 7. Statocyst signals are thus transmitted to uropod motoneurons by two types of descending pathways: one whose operation is affected by the abdominal system and the other which operates independently. The former pathway functions by recruiting intersegmental abdominal interneurons and makes stronger connections with motoneurons than the latter. PMID- 1625220 TI - Regulation of melatonin production by light, darkness, and temperature in the trout pineal. AB - The pineal gland of the rainbow trout, Salmo gairdneri, when kept under in vitro perifusion culture conditions, displays a consistently elevated level of melatonin production in darkness (Gern and Greenhouse 1988). Upon light exposure melatonin production falls and stabilizes at a new lower level that is dependent upon the irradiance of the stimulus. To achieve the maximal response for each irradiance, the duration of the stimulus must exceed 30 min. The response amplitude is maximally sensitive to photons presented over durations of 30-45 min; is very insensitive to shorter light exposures; and is maintained with no evidence of adaptation over longer exposures. Temperature plays a role in regulation of melatonin production both in darkness and during light exposure; increased temperature increases melatonin production in darkness and also increases the sensitivity of the response to light. The action spectrum for the response is best fit by the Dartnall nomogram for a vitamin A1 based rhodopsin with peak sensitivity near 500 nm. The possible adaptive significance of control of melatonin synthesis by light and temperature is considered. PMID- 1625221 TI - Mechanosensory afferents innervating the swimmerets of the lobster. I. Afferents activated by cuticular deformation. AB - The mechanosensory innervation of the lobster (Homarus americanus) swimmeret was examined by electrophysiologically recording afferent spike responses initiated by localized mechanical stimulation of the caudal surface of the swimmeret. Two functional groups of subcuticular hypodermal mechanoreceptors innervate the swimmeret. Afferents of one group innervate the small discrete "ridges" of calcified cuticle lining the margins of both swimmeret rami. Putative ridge receptors are bipolar sensory neurons responding phasically to deformation of the ridge cuticle with the number and frequency of impulses produced dependent on stimulus strength and velocity. Afferents of the second group, which innervate substantial areas of hypodermis underlying the soft, flexible cuticular regions of the swimmeret, were designated "wide-field" hypodermal mechanoreceptors. These neurons have multiterminal receptive fields and respond phaso-tonically to cuticular distortion. The response properties of both types of hypodermal mechanoreceptors imply that they are activated during the characteristic beating movements of the swimmerets. PMID- 1625222 TI - Mechanosensory afferents innervating the swimmerets of the lobster. II. Afferents activated by hair deflection. AB - Feathered hair sensilla fringe both rami of the lobster (Homarus americanus) swimmeret. The sensory response to hair displacement was characterized by recording afferent impulses extracellularly from the swimmeret sensory nerve while deflecting sensilla with a rigidly-coupled probe or controlled water movements. Two populations of hairs were observed: "distal" hairs localized to the distal 1/3 of each ramus and "proximal" hairs near its base. Distal hairs are not innervated by a mechanosensory neuron but instead act as levers producing strain within adjacent cuticle capable of activating a nearby hypodermal mechanoreceptor. Hair deflections of 25 degrees or more are required to evoke an afferent response and this response is dependent on hair deflection direction. The frequency and duration of the afferent discharge evoked are determined by the velocity of hair displacement. Each proximal hair is innervated by a single mechanosensory neuron responding phasically to hair deflections as small as 0.2 degrees in amplitude. Deflection at frequencies up to 5 Hz elicits a single action potential for each hair movement; at higher frequencies many deflections fail to evoke an afferent response. These sensilla, which are mechanically coupled, may be activated by the turbulent flow of water produced by the swimmerets during their characteristic beating movements. PMID- 1625223 TI - The neuroanatomical basis of feeding behavior in the pteropod mollusc, Clione limacina (Phipps). AB - 1. In order to investigate neural mechanisms underlying the switching from hovering-swimming to hunting behavior in the carnivorous mollusc Clione limacina, the innervation of the major muscle bands was studied. The destination of a majority of nerves was traced. 2. Nervous cells sending their processes in the sensory motor nerves were mapped using the retrograde transport of cobalt ions. 3. The combination of morphological investigation, with local extracellular stimulation of groups of cells in semi-intact preparations, provided a detailed description of the functional involvement of the majority of the neural elements in either type of behavior. As a result, detailed diagrams for intracellular investigation of participation of individual cells and functional groups were obtained. PMID- 1625224 TI - Effects of thioridazine on mechanical responses of human vas deferens induced by noradrenaline or potassium. AB - Thioridazine (0.1-10 mumol l-1) inhibited shortening of specimens of human vasa deferentia induced by noradrenaline (100 mumol l-1) or high extracellular potassium (136 mmol l-1). Thioridazine did not inhibit the lengthening response. In Ca(2+)-free media with EGTA (0.5 mmol l-1) similar results were obtained with responses to noradrenaline, but exposure to potassium elicited small contractions that were potentiated by thioridazine. Both shortening and lengthening responses to noradrenaline were antagonized by the alpha-adrenoceptor blockers prazosin (1 10 mumol l-1) and phentolamine (1-10 mumol l-1) and by the Ca2+ antagonists verapamil (10 mumol l-1) and diltiazem (10 mumol l-1). Responses to potassium were virtually abolished by the Ca2+ antagonists. These results show that thioridazine specifically inhibits longitudinal muscle of the human vas deferens and that its action cannot be entirely accounted for by a blockade of voltage gated Ca2+ channels. PMID- 1625225 TI - Effects of ethanol on the decidual cell reaction in rats. AB - The effects of ethanol on uterine sensitivity to induction of decidualization and deciduoma growth were determined. Rats were ovariectomized, given an oestrogen progesterone regimen to optimize induction and growth of deciduoma and randomly assigned to one of three ethanol treatment groups: (i) days 1-4 (pre induction/period of sensitivity), (ii) days 5-9 (post-induction/period of growth), (iii) days 1-9 (periods of sensitivity and growth); or to a control group not treated with ethanol (pair-fed to treated groups). Ethanol (0, 1, 2, or 4 g kg-1) diluted in water was administered by stomach tube on the days prescribed. Decidualization was induced in one uterine horn by intraluminal injection of sodium phosphate buffer. Uterine sensitivity and decidual growth were assessed as cornu weight. Blood alcohol concentrations were measured by gas chromatography. Alcohol treatment reduced uterine sensitivity, but increased deciduoma growth. Blood alcohol concentrations rose to 133 mg% at 30 min, remained high for 90 min and declined to 82 mg% at 120 min. Thus, blood alcohol concentrations sufficient to induce mild intoxication in humans suppressed uterine sensitivity to decidualization and enhanced deciduoma growth in rats. As all ovarian steroid hormone support was exogenous, the effects of ethanol on deciduoma induction and growth were not due to alterations in the hypothalamic pituitary-ovarian axis. PMID- 1625226 TI - Effects of expression of human or bovine growth hormone genes on sperm production and male reproductive performance in four lines of transgenic mice. AB - Reproductive performance was studied in transgenic males from lines expressing and transmitting four hybrid genes: mouse metallothionein-I/human growth hormone (GH) (MT/hGH), MT/hGH placental variant (MT/hGH.V), MT/bovine GH (MT/bGH) and phosphoenolpyruvate carboxykinase/bGH (PEPCK/bGH). Each male was exposed to three normal females for 1 week and to three different normal females for another week. Females were examined for vaginal plugs and necropsied on day 14 of pregnancy. Males were killed for analysis of organ weights, numbers of testicular spermatids, numbers of epididymal sperm and measurements of plasma glucose concentration. Fertility of MT/hGH and MT/hGH.V transgenic males was significantly lower than in normal males, primarily because most males failed to impregnate any females. In females that became pregnant, the numbers of corpora lutea, total fetuses and live fetuses did not differ from those in females mated to normal (nontransgenic) males. Fetal crown-rump length on day 14 of pregnancy did not differ between litters sired by normal or by transgenic males. Weights of testes and seminal vesicles were significantly greater in all four types of transgenic male, but daily sperm production per unit weight (g-1) of testis was not affected and epididymal sperm reserves were either normal or slightly higher than normal. Plasma glucose concentrations were significantly higher in PEPCK/bGH mice than in other mice. Average or individual reproductive performance of transgenic males from the various lines did not correlate with any of the parameters examined except for significantly heavier seminal vesicles in MT/hGH and MT/hGH.V males than in normal males; these transgenic males exhibited a high incidence of infertility. Since hGH and hGH.V, but not bGH, are lactogenic in rodents, it was concluded that chronic stimulation of GH and prolactin receptors by ectopically produced human GHs in transgenic mice compromises male fertility by an unknown mechanism. Reduced fertility of transgenic males with MT/hGH or MT/hGH.V hybrid genes is due to failure to inseminate or impregnate females rather than to reduced numbers of spermatozoa or gross changes in the male reproductive system. PMID- 1625227 TI - Developmental capacity of mouse oocytes matured in vitro: effects of gonadotrophic stimulation, follicular origin and oocyte size. AB - Development of mammalian oocytes is usually correlated with ovarian follicular development. This correlation was tested by determining whether gonadotrophic stimulation of follicular development in immature mice resulted in a coordinated increase in the embryonic developmental capacity of the oocytes. Oocyte cumulus cell complexes were isolated at the germinal vesicle stage from small, medium and large antral follicles of 26-day-old mice and matured and fertilized in vitro. The frequency with which embryos from oocytes from small follicles completed the two-cell to blastocyst transition was lower than for embryos from oocytes from large follicles (33% and 79%, respectively). Germinal-vesicle stage oocyte cumulus cell complexes were isolated from 22-26-day-old mice that were unprimed or primed by injection of equine chorionic gonadotrophin 48 h before isolation. Oocytes were matured in control medium, or in medium containing 1 microgram follicle-stimulating hormone (FSH) ml-1, and then fertilized in vitro. Priming did not increase the number of embryos completing the two-cell stage to blastocyst transition in the 22-day-old group nor did FSH treatment of maturing oocytes when the oocytes were isolated from unprimed 22-day-old mice. In contrast, priming increased the percentage of embryos completing the two-cell stage to blastocyst transition in the 26-day-old group by 20%. FSH treatment of maturing oocytes from the unprimed, 26-day-old group increased the number of embryos completing the transition to the same level as those in the primed 26-day old group, but FSH did not increase the frequency of transition in the primed 26 day-old group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625228 TI - Development from birth to sexual maturity in a semi-free-ranging colony of mandrills (Mandrillus sphinx) in Gabon. AB - This report presents information collected over 7 years (1983-1990) in Gabon, on a breeding group of 14, increasing to 45, mandrills maintained in a rainforest enclosure. Under these conditions, a seasonal cycle of mating (June-October) and birth (January-May) occurred. Females began to exhibit sexual skin swellings at age 2.75-4.5 years (3.6 +/- 0.6 years, mean +/- SD; n = 10) and first delivered offspring when 3.25-5.5 years old (4.4 +/- 0.8 years; n = 9). Gestation periods ranged from 152 to 176 days (167 +/- 9 days; n = 6 accurately dated pregnancies) and interbirth intervals from 11 to 15 months (12.4 +/- 1.3 months; n = 15). Females could reproduce 2 years before attaining adult body weight (10-15 kg) and complete dental eruption by 5.0-5.5 years. Males, by contrast, developed more slowly, reaching adult body weight (30-35 kg) and testicular volume (volume of left testis: 25-30 ml) at 8 years. Consistently high circulating testosterone concentrations (8.17 +/- 2.0 ng ml-1) could be measured by 9 years of age. Fully developed males exhibited fatting of the rump and flanks, as well as striking sexual skin coloration and an active sternal cutaneous gland; little expression of these features was evident during pubertal development. Marked individual age differences occurred with regard to the onset and complete development of these features, suggesting possible interactions between social environment and physical maturation. PMID- 1625229 TI - Ability of nifedipine to prolong parturition in rats. AB - Rats were randomly assigned to treatments: (i) no surgery control; (ii) saline control; (iii) 0.25, 0.5, 1.0 or 2.0 micrograms nifedipine kg-1 min-1; or (iv) 5.0 micrograms ritodrine kg-1 min-1. All drug treatments increased the interval between pup deliveries compared with the no surgery and saline controls. Apparent complete tocolysis was observed in 20, 60, 80 and 80% of the animals receiving 0.5, 1.0 or 2.0 micrograms nifedipine kg-1 min-1 or 5.0 micrograms ritodrine kg-1 min-1, respectively. A positive pharmacodynamic relationship was observed for the nifedipine doses. Analysis of pup viability showed no statistically significant difference among treatments. Treatment with 2.0 micrograms nifedipine kg-1 min-1 gave a delay in pup delivery comparable to that with ritodrine. PMID- 1625230 TI - Androgens in relation to prenatal development and postnatal inversion of the gubernacula in rats. AB - Exposure of male rats to the anti-androgen flutamide during fetal life, from day 10 after conception to the day of birth, allowed quantitatively unaltered development of the gubernacula. Apparently, androgens play no important role or no role at all in their growth. Castration of newborn male rats did not interfere with the inversion during further postnatal life of the gubernacula to create the muscular parts of the scrotum (cremaster muscles). Prenatal exposure to flutamide, followed by castration immediately after birth, also allowed gubernacular inversion and cremaster muscle growth. Neonatal administration of testosterone, after castration at birth, did not enhance gubernacular inversion or promote cremaster muscle growth in infancy or during adulthood. Apparently, postnatal gubernacular inversion and cremaster muscle growth are independent not only of androgens, but also of all testis hormones. Neonatal administration of the potent androgen 5 alpha-dihydrotestosterone propionate suppressed gonadotrophin secretion and, in intact males, inhibited testicular growth. Administration from the day of birth to day 33 delayed testicular descent and enhanced growth of the genital apparatus, but did not affect the size of the cremaster muscles. These experiments indicate that androgens are not involved in the processes that create the cavities into which testes descend to acquire their full reproductive potential. PMID- 1625231 TI - Circadian rhythm of photosensitivity and the adaptation of reproductive function to the environment in two populations of Arvicanthis niloticus from Mali and Burkina Faso. AB - Previous studies have shown that there is a circadian rhythm of photosensitivity in different rodent species of the Sahel (Burkina Faso) and that, despite the low amplitude of seasonal variations in daylength, the photoperiod may control reproductive function. The present investigation of Arvicanthis niloticus provides additional support for this hypothesis. Populations of Arvicanthis niloticus from two regions at the same latitude 1000 km apart but with different climates were studied. Oursi, Burkina Faso, has an arid climate (annual rainfall 315 mm) and Kamale, Mali has a wetter climate (annual rainfall 1114 mm). The circadian rhythm of photosensitivity had the same features in both populations, involving inhibition of testicular activity, but the photosensitive phase began 11 h 30 min after dawn in the population from Burkina Faso and 45 min later in that from Mali. Comparison of these results with the annual variation of daylength showed that the photoperiod inhibits the reproductive activity of A. niloticus from April to December in Burkina Faso and only from mid-May to mid August in Mali. The population of Arvicanthis niloticus living in an environment with a large and seasonally stable food supply (Mali) thus has a longer reproductive period. This corroborates results from field studies on annual variations of population density. PMID- 1625232 TI - Production of prostaglandin by late-gestation porcine placental cells in vitro. AB - Fifteen sows were assigned to three groups of five each, according to gestational age (109 days, 114 days or labour). Two fetuses per sow were chosen at random, and amnion, allantochorion, amniochorion, amniotic fluid and fetal urine were collected. Tissues were enzymatically dispersed and incubated for 1, 2, 3 or 4 h and the prostaglandin (PG) content of the supernatant medium was measured by radioimmunoassay. In general, all placental cell types produced at least three times more prostaglandin E (PGE) and 6-keto-PGF1 alpha than PGF. Production did not vary across gestational age, except that production of 6-keto-PGF1 alpha was lower in cells collected during labour, resulting in a relative increase in PGF and PGE. Aminochorion cells had a lower de novo capacity to synthesize PG than did allantochorion or amniochorion, whereas treatment of allantochorion with preterm amniotic fluid, preterm or term fetal urine resulted in increased PG output. These results demonstrate that porcine placental cells can synthesize and metabolize prostaglandin in late gestation but suggest that their capacity to produce PGI2 (as measured by 6-keto-PGF1 alpha) is lower than for other prostaglandins during labour. PMID- 1625233 TI - Effects of active immunization against a synthetic peptide sequence of the inhibin alpha-subunit on plasma gonadotrophin concentrations, ovulation rate and lambing rate in ewes. AB - Thirty adult Mule (Blue-faced Leicester x Swaledale) ewes were actively immunized against a synthetically produced peptide corresponding to the N-terminus of the alpha-subunit of bovine inhibin conjugated to tuberculin purified protein derivative (PPD). Primary immunization in the late anoestrous period was followed by two booster injections at 5 week intervals. Control groups were either not immunized (n = 15) or received PPD only (n = 15). Ten days after the second booster, oestrus was synchronized using progestagen sponges and ovulation rate was assessed by laparoscopy on days 9-10 of the cycle. Blood samples were taken at the time of each immunization and immediately before laparoscopy. Ewes were mated with fertile rams in mid-November and the resulting conception, pregnancy and lambing rates monitored. All inhibin-immunized ewes generated antibodies that bound 125I-labelled native bovine inhibin (M(r) 32,000), and their plasma follicle-stimulating hormone (FSH) concentrations after the second booster were significantly higher than the preimmunization values (30%; P less than 0.001) and the corresponding value in the controls (25%; P less than 0.025). Inhibin immunization was associated with a 90% increase in ovulation rate (P less than 0.005) and had no adverse effect on conception rate (100%), pregnancy rate (100%) or length of gestation (146 days). However, only a 37% increase (P less than 0.05) in lambing rate was recorded for inhibin-immunized ewes, indicating a higher incidence of wastage of ova, or embryos, or both, in these ewes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625234 TI - Effects of season and testosterone treatment on gonadotrophin secretion and pituitary responsiveness to gonadotrophin-releasing hormone in castrated Romney and Poll Dorset rams. AB - In castrated rams (Romney and Poll Dorset, n = 8 for each breed), inhibition by testosterone treatment (administered via Silastic capsules) of luteinizing hormone (LH) pulse frequency, basal and mean LH concentrations, mean follicle stimulating hormone (FSH) concentration, and the peak and total LH responses to exogenous gonadotrophin-releasing hormone (GnRH) were significantly (P less than 0.01) greater during the nonbreeding than during the breeding season. Poll Dorset rams were less sensitive to testosterone treatment than Romney rams. In rams not receiving testosterone treatment, LH pulse frequency was significantly (P less than 0.05) lower during the nonbreeding season than during the breeding season in the Romneys (15.8 +/- 0.9 versus 12.0 +/- 0.4 pulses in 8 h), but not in the Poll Dorsets (13.6 +/- 1.2 versus 12.8 +/- 0.8 pulses in 8 h). It is concluded that, in rams, season influences gonadotrophin secretion through a steroid-independent effect (directly on hypothalamic GnRH secretion) and a steroid-dependent effect (indirectly on the sensitivity of the hypothalamo-pituitary axis to the negative feedback of testosterone). The magnitude of these effects appears to be related to the seasonality of the breed. PMID- 1625236 TI - Changes related to the oestrous cycle in the expression of endometrial and oviductal proteins of mice. AB - Soluble proteins extracted from the endometria and oviducts of normal sexually mature cycling Swiss Webster mice were analysed by two-dimensional high resolution sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Thirty endometrial and 25 oviductal proteins showed differential expression related to the oestrous cycle. In the endometrium, 19 proteins were maximally expressed in the oestrous phase, and significantly decreased or could not be detected in dioestrus. Eleven additional proteins were more prominent in dioestrus. Most of these endometrial cyclic proteins were acidic. In the oviduct, almost two-thirds of cycle-related, differentially expressed proteins were more strongly expressed in dioestrus and were significantly less prominent or could not be detected in the oestrous phase. In contrast to the endometrial proteins, most of the oviductal cyclic proteins were basic. Fourteen proteins appeared to be identical in both organs, and five of these showed the same cyclic pattern of expression. The remaining cyclic proteins were organ specific and showed uterus- or oviduct-specific changes during the oestrous cycle. Among the cyclic proteins, four endometrial and two oviductal proteins were restricted to oestrus, whereas two endometrial and seven oviductal proteins were restricted to dioestrus. These proteins could serve as markers for specific phases of the oestrous cycle. Our data show that the mouse oestrous cycle is associated with consistent and predictable changes in protein expression in both the endometrium and oviduct. PMID- 1625235 TI - Effects of ovine conceptus secretory proteins and progesterone on oxytocin stimulated endometrial production of prostaglandin and turnover of inositol phosphate in ovariectomized ewes. AB - This study examined the effects of progesterone and intrauterine injection of ovine conceptus secretory proteins (oCSP) on endometrial responsiveness to oxytocin. Twelve ewes were ovariectomized on day 4 of the cycle (oestrus = day 0) and assigned in a 2 x 2 factorial arrangement, to receive either 1.5 mg ovine serum proteins (SP) or oCSP containing 25 micrograms ovine trophoblast protein 1 (oTP-1) (by radioimmunoassay) in 1.5 mg total protein into each uterine horn, via catheters, twice a day on days 11, 12, 13 and 14. Ewes received 200 mg progesterone per day (i.m.) from day 4 to day 10 or 15. Oxytocin-induced prostaglandin F2 alpha was measured as 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) on days 11, 12, 13 and 14 in plasma from three integrated, 10 min (10 ml) blood samples (0-10, 10-20, 20-30 min) obtained after intravenous injection of 20 iu oxytocin, and in a pre-oxytocin (-10 to 0 min) sample collected via an indwelling jugular catheter. The pre-oxytocin samples were also assayed for progesterone. Oxytocin-induced turnover of inositol phosphate was determined in endometrium on day 15 after hysterectomy. In ewes receiving progesterone to day 10, plasma progesterone decreased from about 12 to 2 ng ml-1 (SEM +/- 2.6) during the treatment period (days 11-14), but remained high (12-20 +/- 2.6 ng ml-1) in ewes that received progesterone to day 15. Intrauterine injection of oCSP resulted in high basal concentrations of PGFM on days 12 and 13 compared with SP-treated ewes (P less than 0.01). Treatments with progesterone did not affect basal PGFM concentrations. Treatment with oCSP abolished oxytocin induced endometrial secretion of prostaglandin only if progesterone was maintained to day 15 (P less than 0.01); in ewes receiving such treatment, oCSP inhibited (P less than 0.01), but SP did not inhibit, oxytocin-induced endometrial turnover of inositol phosphate (P less than 0.06), which was greater in ewes treated with progesterone to day 10 than in those treated to day 15 (P less than 0.05). Ewes that responded to oxytocin with increased PGFM exhibited increased oxytocin-stimulated turnover of inositol phosphate on day 15. These results indicate that the antiluteolytic action oTP-1 exerts on the endometrium requires progesterone and that this mechanism involves inhibition of oxytocin stimulated turnover of inositol phosphate. PMID- 1625238 TI - The fate of DNA injected into mammalian oocytes and zygotes at different stages of the cell cycle. AB - The stability of exogenous DNA microinjected into the cytoplasm at different stages of the meiotic cycle and after pronuclear formation was examined in ungulate species. Metabolism of the injected 1201 base pair (bp) DNA was examined by Southern blotting. Similar levels of metabolism of the injected DNA were detected in pig, sheep and bovine oocytes before germinal vesicle breakdown, in which about 30-40% of detected DNA was ligated into higher-molecular-weight forms. Porcine metaphase oocytes and pronuclear zygotes showed a reduced ability to ligate the exogenous DNA. In contrast, sheep and bovine metaphase oocytes and zygotes showed increased levels of ligation and, at the pronuclear stage, generated significant amounts of extremely large (greater than 15 kbp) ligation products. These results are discussed in the context of maternal precursors and metabolic activities in the egg. PMID- 1625237 TI - A new technique for the precise location of lactate and malate dehydrogenases in goat, boar and water buffalo spermatozoa using gel incubation film. AB - Gel incubation film, which contained gelatin to prevent the diffusion of enzyme during chemical reaction and phenazine methosulfate to operate as a hydrogen acceptor between NADH and tetrazolium, was used and light microscopy revealed that lactate dehydrogenase was located in the head and tail of the spermatozoa as well as in the midpiece, whereas malate dehydrogenase was confined to the midpiece in spermatozoa of the animals examined. In goat spermatozoa, lactate dehydrogenase was associated mainly with the inner acrosomal membrane in the head, the mitochondrial matrix in the midpiece and with flagellar fibrils in the tail, whereas malate dehydrogenase was present only in the mitochondrial matrix. PMID- 1625239 TI - Characterization of glutamine uptake in mouse two-cell embryos and blastocysts. AB - Mouse two-cell embryos and blastocysts take up [3H]glutamine in vitro at a constant rate for at least 15 min, depending on the concentration of glutamine and developmental stage of the embryo. Uptake by two-cell embryos can be resolved into two saturable components. The major contributing system is Na+ independent, inhibited by alanine, methionine, 2-amino-2-norbornanecarboxylic acid (BCH) or leucine and has a Km of 3856 +/- 672 mumols l-1 and Vmax of 436 +/- 58 fmol per embryo per 10 min. These features are characteristics of the ubiquitous system L transporter. The second component is Na+ dependent with Km of 1064 +/- 914 mumols l-1 and Vmax 107 +/- 47 fmol per embryo per 10 min. Similar Vmax and inhibition of this component by glycine suggest a low reactivity with the gly-system. Blastocyst uptake of glutamine is mainly by a Na(+)-dependent saturable mechanism with Km of 524 +/- 75 mumols l-1 and Vmax of 1264 +/- 101 fmol per embryo per 10 min which is inhibited by alanine, isoleucine, leucine and BCH, features characteristic of the system B0,+. The increase in uptake capacity as a consequence of the appearance of the system B0,+ may be related to increased metabolic requirements for glutamine, in the rapidly expanding blastocyst. PMID- 1625240 TI - Menstruation in short-tailed fruit bats (Carollia spp.). AB - Uterine function was assessed histologically in Carollia spp. removed from a laboratory breeding colony. The uteri of periovulatory bats examined on days 1-3 post coitum varied considerably depending upon whether regressing corpora lutea were present. In females lacking such corpora lutea, the endometrium was shallow and proliferative. In most of the bats having regressing corpora lutea, the endometrium was thicker and necrotic portions of the superficial lamina functionalis were being sloughed off with associated bleeding (i.e. in the form of a true menstrual process). The presence of regressing corpora lutea and well developed endometria in these animals indicated that short-tailed fruit bats are spontaneous ovulators with a functional luteal phase to their cycles. Menstruation was also observed in some females that were not periovulatory, or that lacked regressing corpora lutea. The endometrium was not vascularized by spiral arterioles, but it did contain distinctive granulocytes similar to those observed in catarrhine primates and other menstruating bats. Most endometrial growth occurred after ovulation and, in pregnant animals, was associated with retention of the embryos in the oviducts for approximately 13-16 days. Carollia perspicillata normally produces one young at a time, after a gestation period of about 4 months, and is a seasonal breeder in the wild. Menstruation probably provides this bat with an efficient mechanism for eliminating a well-developed endometrium from its simplex uterus in the event of fertilization failure or early embryonic loss. This may give the female another chance to establish a pregnancy and produce an infant at a reasonably opportune time during the same breeding season. PMID- 1625241 TI - Effect of different fractions of seminal plasma on the fertilizing ability of fowl spermatozoa stored in vitro. AB - This paper describes the effects of whole seminal plasma and of dialysed seminal plasma on the fertilizing ability of fowl spermatozoa stored for 24 h at 4 degrees C. The fertilizing ability of fowl semen diluted 1:1 with Beltsville Poultry Semen Extender and stored for 24 h at 4 degrees C was enhanced after replacement of the homologous seminal plasma by the diluent (89 versus 77% fertilization rate). Better results were obtained with seminal plasma dialysed against water before sperm storage to discard the less than 1 kDa or the less than 50 kDa fractions. It was concluded that low molecular weight seminal plasma fractions could damage the fertilizing ability of spermatozoa during storage at 4 degrees C, whereas high molecular weight fractions appeared to enhance fertilizing ability. PMID- 1625242 TI - Isolation and culture of glandular epithelial and stromal cells from the endometrium of mares. AB - Glandular epithelial and stromal cells were isolated from the endometrium of mares by collagenase digestion and were incubated on plastic for 7-9 days until the cells formed confluent monolayers. The cells differed in morphology: epithelial cells appeared polyhedral and stromal cells were spindle like. The monolayers were incubated in the presence and absence of oxytocin. Medium was removed from wells after 2, 8 and 24 h of incubation. Concentrations of prostaglandin F (PGF) in the medium increased significantly during this time. Glandular epithelial cells produced significantly more PGF than did stromal cells. Both types of cell responded significantly to oxytocin stimulation by increased secretion of PGF; the response of glandular epithelial cells tended to be greater than that of stromal cells. Secretion of PGF by cultured cells was not affected by cycle stage or pregnancy. PMID- 1625243 TI - Differential binding of (+) and (-) gossypol to plasma protein and their entry into rat testis. AB - Concentrations of (+) and (-) gossypol were measured by high performance liquid chromatography after they were incubated with plasma proteins in vitro. The concentration of (-) gossypol decreased more than the concentration of (+) gossypol. A similar decrease in free gossypol concentrations in the blood plasma of rats was observed after intravenous infusion of gossypol enantiomers. The concentration of (-) gossypol was also found to be lower than the concentration of (+) gossypol at the blood-testis barrier. The biological effect of (-) gossypol probably results from its stereospecific binding to extra- and intracellular proteins in vivo and inhibition of the biological activity of some proteins. PMID- 1625244 TI - Evidence from the oestrous cycle for male-induced ovulation in Bettongia penicillata (Marsupialia). AB - Female brush-tailed bettongs (Bettongia penicillata) housed in a breeding group of one male and one to three females had an average gestation period of 21.2 days (n = 58) and parturition was followed within 24 h by oestrus and mating. If a young was not born as a result of the mating, oestrus recurred after about 21.7 days (n = 12). From removal of pouch young to birth was 17.5 days, on average (n = 85), in females that had mated post partum, but most females that were isolated from a male before parturition returned to oestrus about 6.6 days after simultaneous removal of pouch young and return to the male (n = 9). Females housed in female-only groups appeared not to come into oestrus or to do so irregularly. These females, when returned to the male, usually came into oestrus within 10 days. These data provide evidence that, in most females of B. penicillata, ovulation does not occur in the absence of a male and that previously isolated females return to oestrus within 10 days of return to the male. PMID- 1625245 TI - Evidence from plasma progesterone concentrations for male-induced ovulation in the brush-tailed bettong, Bettongia penicillata. AB - Female brush-tailed bettongs, Bettongia penicillata, were housed with either an intact or vasectomized male or isolated from males in the peripartum period. Development of the quiescent corpus luteum formed at the post partum oestrus was initiated by removing the pouch young. Blood samples for analysis of plasma progesterone were collected from the females 2 days before removal of pouch young, daily for 5 or 6 days and then 2-3 times each week until 19 days after removal of pouch young. Plasma progesterone profiles were similar in pregnant and nonpregnant cycles. There was an early progesterone peak (1206 +/- 121 pg ml-1, mean +/- SEM; n = 16) between days 2 and 5 after removal of pouch young, and a second period of high concentrations (greater than 800 pg ml-1) before birth on day 17.4 +/- 0.2 (n = 16). The interval between the early peak and birth was 14 or 15 days. On five of 34 occasions, no increases in plasma progesterone concentrations occurred after removal of pouch young. On 12 of 15 occasions for 13 females that had been isolated from males post partum, plasma progesterone concentrations also remained low (less than 100 pg ml-1) and did not change after removal of pouch young. Females that showed no increases in plasma progesterone concentration after removal of pouch young had significantly lower (P less than 0.001) plasma progesterone concentrations while lactating than those females that did undergo a cycle after removal of pouch young (60 +/- 4 pg ml-1, n = 17 and 225 +/- 23 pg ml-1, n = 30, respectively). Females isolated from males post partum, and monitored until day 12 after removal of the pouch young, and that showed no increases in progesterone in this period, had ovaries that contained no corpus luteum, only corpora albicantia and numerous atretic or developing follicles. We conclude that brush-tailed bettongs are induced ovulators, a characteristic described for only one other marsupial, Monodelphis domestica, from South America. PMID- 1625246 TI - Hormonal evidence for induced ovulation in Monodelphis domestica. AB - Breeding activity in the South American grey opossum, Monodelphis domestica, is stimulated by the presence of males. This study presents the first analysis of changes in concentrations of plasma progesterone during pregnant and nonpregnant cycles. In Expt 1, females were paired with either intact or vasectomized males to stimulate a reproductive cycle, or were isolated from males. Within 4-8 days of pairing, females showed marked changes in the size of the urogenital opening (vulva), which were paralleled by similar changes in body weight (11.4 +/- 2%; mean +/- SEM; n = 13). There was a second increase and decrease in body weight (21.7 +/- 3.3%; n = 13) in pregnant and nonpregnant cycles during the luteal phase of the cycle. Changes in concentrations of plasma progesterone, determined from samples collected three times a week, were similar in pregnant and nonpregnant cycles. Plasma progesterone concentration, which was increased for 15 18 days, showed two distinct peaks. The first peak, 3-4.5 ng ml-1, occurred immediately after the decrease in vulval swelling, and the second peak (1-2 ng ml 1) occurred 8-12 days later. Concentrations of plasma progesterone were low before parturition occurred. Females isolated from males for 35 days showed no changes in body weight or vulval swelling and concentrations of plasma progesterone remained undetectable. In Expt 2, concentrations of luteinizing hormone (LH) in plasma were determined twice a day for the first few days after pairing. In three of five females an LH peak was detected coincident with the maximal swelling of the vulva. PMID- 1625247 TI - Genetic susceptibility to chlamydial salpingitis and subsequent infertility in mice. AB - Groups of mice from genetically defined inbred strains were infected genitally with a pathogenic human strain of Chlamydia trachomatis and their subsequent fertility was compared. The CBA, C3H (H-2o) and C3H/He-mg (H-2k) mice were less fertile than control mice, at least up to 6 months after infection. In contrast, fertility was not impaired in BALB/c mice or in congenic BALB/K mice, which had the H-2k haplotype. Reduced fertility was paralleled by the extent of histological oviductal inflammation in mice of each strain. No salpingitis was seen 21 days after infection in the BALB strains, but lesions were apparent in CBA and C3H strains up to about 70 days after inoculation and these sometimes developed into hydrosalpinges. These results indicate that susceptibility to chlamydial salpingitis and subsequent infertility is under genetic control. This control was not simply associated with the major H-2 gene complex, as mouse strains of the same haplotype (H-2k) differed in susceptibility. The fertility of BALB/c (H-2d) and BALB/K (H-2k) strains was no different from that of controls, and congenic C3H mice of differing H-2 haplotypes (H-2k and H-2o) showed reduced fertility. Although all the infected F1 (BALB/K x C3H/He-mg) mice produced litters at the same rate as untreated controls, the litters were considerably smaller. This was due to the occurrence of unilateral pregnancies in the mice inoculated under the ovarian bursae and possibly also to early fetal death in mice inoculated directly in the uterus. These findings emphasize the importance of early diagnosis and treatment of infection of the lower genital tract of women. PMID- 1625248 TI - Synchronous division of mouse two-cell embryos with nocodazole in vitro. AB - Mouse two-cell embryos were cultured in a medium supplemented with nocodazole or colcemid for 12.5-14.5 h in vitro, and development after elimination of these drugs was examined. All embryos cultured with nocodazole stopped at the metaphase of the second cell cycle. When nocodazole was removed, almost all embryos divided to the normal four-cell stage within 1 h and then developed into blastocysts (98%). The proportion of embryos that developed into young after transfer to recipients was not significantly different from the control (35 versus 36%), but the developmental ability of the embryos treated with colcemid was reduced, especially after transfer to recipients. PMID- 1625249 TI - A comparison of rate and uniformity of embryo development in Meishan and European white pigs. AB - A comparison was made of the rate and uniformity of development of embryos recovered from Meishan and European white sows. The time of ovulation was estimated to be 34.3 and 49.0 h after the onset of oestrus in large white and Meishan sows, respectively. Embryos were recovered from a total of 38 Meishan and 37 European pigs between 18 and 219 h after the estimated time of ovulation. Embryos recovered after 18-59 or 44-82 h were classified into one of 11 stages (from early fertilization to early blastocyst), and the maximum blastocyst diameter was measured for embryos recovered 140-219 h after ovulation. There was no evidence of a difference between the genotypes in the stage or size of embryos at these times or of large differences between the genotypes in the extent of variation in embryo stage within females, although a minority of European white females had very variable embryos. As the differences between the embryos of the Meishan and the European white were small, it seems unlikely that greater uniformity of Meishan embryo development is a major cause of the higher prenatal survival in that breed. PMID- 1625251 TI - Effects of treatment with butylated hydroxytoluene on the susceptibility of boar spermatozoa to cold stress and dilution. AB - Boar spermatozoa acquired resistance to cold shock immediately after exposure to 2.0 mmol butylated hydroxytoluene (BHT) l-1 when Beltsville thawing solution was used as a basic diluent, as judged by motility (the proportion of motile spermatozoa) and acrosomal integrity. The concentration of BHT could be reduced to 0.2 mmol l-1 without decreasing the protective action. However, motility was altered in the presence of greater than 0.15 mmol BHT l-1. Beltsville freezing 5 (BF5) diluent was more effective than Beltsville thawing solution in protecting spermatozoa from cold shock, but addition of BHT to BF5 diluent did not affect the motility and acrosomal morphology of spermatozoa before or after cold shock. Dilution of BHT-treated spermatozoa with BF5 diluent did not restore motility and did not afford further protection against cold shock; it was detrimental to spermatozoa treated with 2 mmol BHT l-1 for greater than 15 min. Egg yolk or lecithin had a detrimental effect. When spermatozoa were treated with 0.05-0.10 mmol BHT l-1 before slow cooling to 5 degrees C, the progressive motility and acrosomal integrity were maintained better after storage for 6 days than in untreated spermatozoa. PMID- 1625250 TI - A pseudoseasonal reproductive strategy in a tropical rodent, Peromyscus nudipes. AB - A population of cloud forest mice (Peromyscus nudipes) at latitude 10 degrees N near Monteverde, Costa Rica, was sampled four times by live-trapping twice during the 7-8 month wet season and twice during the 4-5 month dry season in 1989 and 1990. Body weights were lower during the early part of the dry season in males and throughout the dry season in females than at other times. Testes and seminal vesicles were somewhat lighter early in the dry season, but epididymal spermatozoa were abundant in most males throughout the year. Adult females ovulated, mated and became pregnant in the wet and dry seasons, but young were produced only during the wet season. Most embryos failed to implant during the dry season, and the few that did complete implantation were reabsorbed before midpregnancy. Apparently, every year, the females in this population spend several months actively engaged in a behavioural and metabolically costly process that is doomed to be unsuccessful. This reproductive strategy is termed pseudoseasonal, because reproductive success is highly seasonal, but attempts to reproduce are nonseasonal. Implantation failures similar to those seen in the wild were induced in the laboratory using mild restriction of food or water. Field evidence points to food restriction as the more important cause of pregnancy losses in the wild. Exposure to the gradually changing daylengths typical of Costa Rica had no effect on the production of young by adults, and maintenance on light cycles of 8 h light: 16 h dark, 11 h light: 13 h dark, 13 h light: 11 h dark and 16 h light: 8 h dark had no effect on the reproductive development of young animals of either sex. PMID- 1625252 TI - Induction of immunity to spermatozoa in male domestic fowl and effects on fertility. AB - Male fowl were immunized intravenously (i.v.) or intramuscularly (i.m.) with spermatozoa to assess the effects of immunity to spermatozoa on fertility. Histological and immunofluorescence evaluations of testis and ductus deferens tissues after 24 weeks of immunizations revealed immune cell infiltration and immunoglobulin associated with spermatozoa. The long-term immunization regimen resulted in significant antisperm antibody titres in the immunized groups. When semen from i.v.-immunized males was used to inseminate females, fertility over 7 days was reduced (P less than 0.05). A subsequent experiment using a 10-week i.v. immunization scheme also led to high antisperm titres. Spermatozoa from these males were characterized by lower fertility and duration of fertility than those of controls (P less than 0.05). As in mammals, a reduction in fertility may result from exposure of avian males to sperm antigens. PMID- 1625253 TI - Effects of age, photoperiod and follicle-stimulating hormone on lactate production by cultured Sertoli cells from prepubertal Siberian hamsters (Phodopus sungorus). AB - To define a functional difference in Sertoli cells of animals exposed to different photoperiodic conditions, we isolated Sertoli cells from the testes of juvenile Siberian hamsters and cultured them in serum-free medium. In all age groups studied, Sertoli cells isolated from hamsters with delayed and normal puberty responded to follicle-stimulating hormone (FSH) with an increase in lactate production. The increase in lactate production induced by 1000 ng FSH ml 1 was significantly greater in Sertoli cells isolated from hamsters with delayed puberty than in those with normal puberty. These results suggest that Sertoli cells of Siberian hamsters exposed to short photoperiod in vivo may respond to increases in plasma FSH concentrations associated with photostimulation or spontaneous sexual maturation by an increase in secretory activity that may be critical for the initiation of spermatogenesis. PMID- 1625254 TI - Frequent semen collection and sperm reserves of the male Angora goat (Capra hircus). AB - Semen was collected from six mature and sexually rested Angora bucks at one-hour intervals five times a day on each of 5 consecutive days in the breeding season. There was a marked decline in semen volume (P less than 0.001), sperm concentration (P less than 0.05) and number of spermatozoa (P less than 0.001) on consecutive days. Successive ejaculates within days differed only in number of spermatozoa (P less than 0.001). The following year at the beginning of the breeding season, the weights of testes and epididymides and the reserves of spermatozoa in these parts were examined after slaughter of the six bucks. The mean number of spermatozoa in the paired testes, capita, corpora and caudae of the epididymides were (22.8 +/- 1.24) x 10(9), (9.4 +/- 1.19) x 10(9), (3.4 +/- 0.22) x 10(9) and (35.0 +/- 2.21) x 10(9), respectively. Epididymal reserves of spermatozoa were correlated with testicular weight (r = 0.50, P = 0.01) and number of spermatozoa in the testes (r = 0.42, P = 0.07), but not with epididymal weight. The daily production of spermatozoa per animal in the breeding season was estimated to be 4.0-6.4 x 10(9). PMID- 1625255 TI - Society for the Study of Fertility. Annual conference. Glasgow, 15-17 July 1992. Abstracts. PMID- 1625256 TI - Excessive fear of dilute radiation. PMID- 1625258 TI - The portrayal of the physician in non-medical literature--the physician and his family. PMID- 1625257 TI - Graft-versus-host disease following liver transplantation. PMID- 1625259 TI - Acute urinary retention secondary to carcinoma of the prostate. Is initial channel TURP beneficial? AB - Over a 2-year period patients presenting with acute urinary retention secondary to locally advanced prostate carcinoma (stage T3/T4) were randomized to one of two treatments. Ten patients underwent channel transurethral resection of prostate (TURP) and bilateral orchidectomy, 12 patients underwent bilateral orchidectomy alone. Treatment by channel TURP and bilateral orchidectomy was complicated by difficulties in voiding in four patients, one requiring a further TURP. Ten of the 12 patients were voiding well one month following bilateral orchidectomy alone. Only two patients in this group required TURP. In patients with acute urinary retention secondary to prostate carcinoma, in whom hormonal manipulation is thought appropriate due to bulk of local tumour or metastatic disease, channel TURP may confer extra morbidity and therefore be held in reserve for those patients unable to void after hormonal manipulation. PMID- 1625260 TI - Percutaneous endoscopic gastrostomy in 41 patients: indications and clinical outcome. AB - Percutaneous endoscopic gastrostomy, under local anaesthetic, was successfully used in 40 out of 41 patients referred for nutritional support. The indications were neurological disorders of swallowing in 32 patients, head and neck cancer in four patients and supplemental feeding in a miscellaneous group of five patients. The main complications of this procedure were one failed insertion and one peritubal infection. At prospective follow-up, the tube continued to function in 16 patients (seven at home) a mean of 184 days post-insertion (range 6-610 days). In 11 patients resumption of swallowing at a mean of 122 (20-390) days allowed tube removal. Thirteen patients died from their disease, a mean of 96 (12-320) days post-insertion. Patient tolerance and patient and carer satisfaction have been excellent and early results suggest that recovery of speech and swallowing in acute neurological disorders may be enhanced. Percutaneous endoscopic gastrostomy should be performed in all patients referred for a gastrostomy and should be considered in all patients requiring long-term tube feeding. PMID- 1625261 TI - Use of a bandage contact lens in perforating injuries of the cornea. AB - Four cases of perforating corneal injuries as a result of work-related injuries are presented. All were managed with a bandage contact lens and surgical intervention was avoided. Topical pilocarpine was used to free incarcerated iris in two cases. All patients received a course of broad-spectrum systemic antibiotics, and also used topical preservative-free chloramphenicol for the duration of contact lens wear. No lens related complications occurred. Final unaided visual acuities were the same or better than at presentation. PMID- 1625262 TI - Inappropriate circumcision referrals by GPs. AB - One hundred and twenty boys were referred by GPs over a 12-month period to a paediatric urologist for circumcision. The reasons for referral were: ballooning in 36, non-retraction in 28, balanoposthitis in 36 or a combination in 15. On examination 53% had a retractile, 21% a partially retractile and 21% a non retractile foreskin. Six patients had obvious balanitis xerotica obliterans. Only one quarter of the patients required a circumcision. The penis was not examined by the referring doctor in 15 patients. The implications of this survey are that a large proportion of general practitioners have difficulty in discriminating between a true phimosis and a developmentally non-retractile foreskin. This diagnostic inaccuracy was greatest when the referring doctor did not examine the patient. PMID- 1625263 TI - Benefits of training junior physicians to detect diabetic retinopathy--the Glasgow experience. AB - The accuracy and appropriateness of 115 consecutive referrals by non-consultant physicians to a specialist Diabetic Retinopathy Clinic were assessed in a retrospective study. The source of the referrals was masked throughout the study. Referrals were classed as 'appropriate' or 'inappropriate' for patient management, and the referral diagnosis (where specified) was compared with the ophthalmologist's initial assessment. It was graded as 'correct', 'partly correct' and 'incorrect'. Referrals from physicians who had received 40-50 hours of outpatient training in the Diabetic Retinopathy Clinic (group A, n = 49) were compared with referrals from doctors without this special instruction (group B, n = 66). Referral was deemed 'appropriate' in 32 (65%) of group A referrals, but in only 22 (33%) of group B (chi 2 = 11.54, df = 1, P less than 0.001). Referral diagnosis (when expressed) was graded as 'correct' in 28 (67%) of group A referrals compared with only 12 (30%) of group B, being 'incorrect' in 10 (25%) of group B referrals and just two (4.5%) of group A (chi 2 = 12.9, df = 2, P less than 0.005). Regular fundoscopy with accurate assessment and appropriate action is vital to prevent loss of vision in diabetic patients. Short-term outpatient training in a Diabetic Eye Clinic leads junior physicians to more appropriate referral and more accurate referral diagnosis. PMID- 1625264 TI - Health of a team competing in the 1990 World Solar Car Challenge. AB - The health of a team participating in the 1990 World Solar Car Challenge was recorded for 10 of the 11 race days. Morbidity was collected during daily consultations with the team doctor and the diagnoses were later converted to the ICPC code. Team members' self-perceived health status was also recorded daily, using the Nottingham Health Profile. Team drivers consulted the doctor more often than the support staff and the three full-time drivers had significantly more diagnoses than the support staff. The Nottingham Health Profile scores on sleep, energy and emotional reactions showed correlations between higher minimum temperatures and sleep for all team members and for the three full-time drivers, there were significant correlations between increasing maximum temperatures and emotional reaction scores. The morbidity records and perceived health scores reflect the conditions of the race. Twenty-five per cent of full-time driver consultations dealt with skin, eyelid or finger infections probably caused by the lack of washing water. The scores on sleep and emotional reactions were affected by temperature and previous research reports degradation in concentration and dual tasks with increasing temperature. This may account for the difficulty some drivers had in continuing their shifts. Close supervision of the drivers and the recording of their perceived health status helped reduce the health problems of the team. PMID- 1625265 TI - Final year medical students' knowledge of practical nutrition. AB - An entire final-class of medical students was set a 6-part question on dietary advice to patients as commonly seen in general practice. The marks were scored by a formal, agreed system. Eighty-two per cent failed though only 2% failed the whole exam. The teaching of practical nutrition needs to be improved. PMID- 1625266 TI - Familial colorectal cancer: discussion paper. PMID- 1625267 TI - The Sherlock Holmes paradigm--detectives and diagnosis: discussion paper. PMID- 1625268 TI - Cerumen: its fascination and clinical importance: a review. PMID- 1625269 TI - 'Value in love poetry?'--an appraisal of Ovid's 'Amores'. PMID- 1625270 TI - Imaginary conversations from the history of medicine: Robert Koch and Wilhelm Conrad Rontgen. PMID- 1625271 TI - Necrobiotic xanthogranuloma with orbital involvement. PMID- 1625272 TI - Idiopathic megarectum treated by Duhamel's operation. PMID- 1625273 TI - Gaucher's disease. PMID- 1625274 TI - Psittacosis and acute thrombocytopenic purpura. PMID- 1625275 TI - Implantation metastasis from adenocarcinoma of sigmoid colon into fistula in ano. PMID- 1625276 TI - Co-existing Listeria and pneumococcal infection in a chronic alcoholic. PMID- 1625277 TI - Ophthalmic manifestations of metastatic carcinoma of the breast. PMID- 1625278 TI - 7th European Conference on Clinical Haemorheology. PMID- 1625279 TI - Haemorheological treatment of ischaemia--facts or fancy? PMID- 1625280 TI - The COMA report: sugars and dental caries. PMID- 1625281 TI - Warts and all. PMID- 1625282 TI - Inhalation therapy in asthma. PMID- 1625283 TI - Inhalation therapy and asthma. PMID- 1625284 TI - Doctors' dress. PMID- 1625285 TI - Neonatal cleft lip repair. PMID- 1625286 TI - Unilateral choanal atresia. PMID- 1625287 TI - Female body size, parity, and malaria infection of Anopheles maculatus (Diptera: Culicidae) in peninsular Malaysia. AB - The relationship among body size (as indicated by wing length), age (as indicated by parity dissections), and malaria infection were observed in host-seeking Anopheles maculatus Theobald females collected in aboriginal villages of peninsular Malaysia. Both ELISA and salivary gland dissections were used to determine malaria infection. The wings of parous females were significantly longer than those of nulliparous females, suggesting that larger females live longer than smaller ones, and thus have a higher vectorial capacity. Body size differences were not detected between infected parous and uninfected parous females. Females infected with only oocysts were significantly larger than females infected with sporozoites. No correlation was found between the number of oocysts or sporozoites and body size in this small sample. PMID- 1625288 TI - Gonotrophic cycle and survivorship of Anopheles albimanus (Diptera: Culicidae) in southern Mexico. AB - The length of the gonotrophic cycle of Anopheles albimanus was estimated by 12 mark-release-recapture studies conducted in corrals in southern Mexico from 1987 to 1990. The initial set of three mark-release studies indicated that the gonotrophic cycle takes at least 4 d based on the day when gravid mosquitoes were first recaptured. However, in later experiments, mosquitoes recaptured seeking hosts at 48 h after release were in Sella's and Christophers' stages I and II, but parity rates had nearly doubled, indicating that eggs may have developed in less than 48 h and that mosquitoes returned to refeed immediately following oviposition. Two gonotrophic cycles probably exist, one of 48 h dominated by parous mosquitoes and one of 4 d comprised of nulliparous, pregravid mosquitoes. Daily survivorship was estimated by regression from the decrease in the daily recapture rate (0.46-0.68) was less than that estimated by the parity rates (0.67 0.69), with no important differences found between wet and dry seasons. Estimates of the probability of a mosquito living long enough to transmit malaria were 2% (range, 1.8-2.5%). PMID- 1625289 TI - Scanning electron microscopic observations of Anopheles albimanus (Diptera: Culicidae) eggs. AB - To investigate the existence of subspecies of Anopheles albimanus Wiedeman in southern Mexico, the egg morphology of specimens obtained from several field populations and from insectary-adapted colonies of uniform pupal phenotype was examined. Scanning electron microscopic observations have shown that the eggs of An. albimanus are polymorphic in respect to the size and shape of their floats, but not in their ornamentation. Four types of eggs were found. Differences in the proportion of the various morphological types were statistically significant, although proportions of egg types were variable among individuals within the same population. These observations are suggestive of distinctive populations and warrant further studies using more sensitive methods to investigate sibling species in An. albimanus sensu lato. PMID- 1625290 TI - Cellular responses of laboratory mice to feedings of Ornithodoros talaje (Acari: Argasidae) larvae. AB - Studies were carried out in which laboratory mice were subjected to sequential feedings by slow feeding Ornithodoros talaje (Guerin-Meneville) larvae to detect and characterize the host cellular response. After the first exposure, histological evidence showed a strong neutrophil infiltration at the site of attachment and feeding. By the third exposure, a marked shift to lymphocytes was noted in the mouse tissues using histological preparations of the feeding ticks. Lymphocyte proliferation tests also provided indirect evidence of a host lymphocyte response as a result of the three tick exposures and feedings. PMID- 1625291 TI - Dormancy, embryogenesis, and hatching of eggs of Prosimulium kiotoense (Diptera: Simuliidae) under natural and experimental conditions. AB - The egg dormancy and embryogenesis of the univoltine black fly, Prosimulium kiotoense Shiraki, in southwestern Japan were examined under natural and laboratory conditions. Eggs laid in April remained dormant until August (approximately 14 wk after oviposition). Hatching commenced in early October (after 23 wk), when air and water temperatures decreased to 20 and 15 degrees C, respectively, and continued until mid-December (32 wk) in the field. Laboratory experiments showed that lower temperatures (10 and 14 degrees C) supported embryogenesis similar to that observed in the field. In contrast, higher temperatures (18 and 22 degrees C) retarded or completely suppressed embryogenesis after the termination of dormancy. However, completion of dormancy was accelerated when eggs were exposed experimentally to these higher temperatures for 3-12 wk, then returned to a constant low temperature (14 degrees C). Daylength did not affect the maintenance and termination of dormancy. Therefore, temperature played an important role differentially affecting completion of dormancy and postdormancy development. Variable lengths of developmental periods among egg batches under the same conditions indicated possible genetic control of dormancy intensity. PMID- 1625292 TI - Aedes aegypti (Diptera: Culicidae) vision: response to stimuli from the optical environment. AB - Although Aedes aegypti (L.) are capable of some wavelength discrimination, behavioral experiments demonstrated that color was not a stimulus to which they responded. Optical stimuli that did affect Ae. aegypti behavior were luminous reflectance, vertical contrast, and movement. Stationary objects of low reflectance and solid color were the most attractive to males and females. PMID- 1625293 TI - Quantitative evaluation of sampling methods for Ixodes dammini and Amblyomma americanum (Acari: Ixodidae). AB - Three tick-sampling methods (dry ice-baited tick traps, cloth drags, and ambulatory human host) were evaluated to determine which technique yielded the greatest capture of host-seeking stages of Ixodes dammini Spielman, Clifford, Piesman & Corwin and Amblyomma americanum (L.). The most reliable method, catching more stages and significantly more numbers of I. dammini and A. americanum; was dry ice-baited tick traps. There were no significant differences between the drag and human-host methods for any stage of ticks (I. dammini and A. americanum) collected. The numbers of ticks caught during the study were 5,052 by dry ice-baited tick traps, 199 by cloth drags, and 89 by ambulatory human host. PMID- 1625294 TI - Morphological and functional classification of the hemocytes of adult female Simulium vittatum (Diptera: Simuliidae). AB - Morphology and function of the hemocytes of 1-d-old, female Simulium vittatum Zetterstedt were studied using light and scanning electron microscopy. Four types of hemocytes, comparable with those of other medically important Diptera, were identified: prohemocytes, plasmatocytes, granulocytes, and spherulocytes. Plasmatocytes and granulocytes contained neutral red granules, but only granulocytes exhibited significant acid phosphatase activity. Plasmatocytes and granulocytes were identified as the primary phagocytes: plasmatocytes and granulocytes of bacteria in vitro and granulocytes of human red blood cells in vivo. Granulocytes also were observed attached to and degranulating into fat body and hemopoieticlike tissue fragments, perhaps assisting in the mobilization of nutrients for egg development and in the release of immature hemocytes into circulation. PMID- 1625295 TI - Reproductive and metabolic differences between Aedes aegypti and Ae. albopictus (Diptera: Culicidae). AB - Aedes albopictus (Skuse) females were more likely to develop eggs after they ingested small blood meals than were Aedes aegypti (L.) when both species were maintained under the same suboptimal adult nutritional regimen. The longevity of adult female Ae. albopictus under conditions of starvation was also significantly greater than that of Ae. aegypti. Analyses of total body proteins, lipids, and glycogen indicated that the increased reproductive efficiency of Ae. albopictus may be a result of its greater reserves accumulated during a longer larval period. PMID- 1625296 TI - Ecological observations on the 1989 outbreak of St. Louis encephalitis virus in the southern San Joaquin Valley of California. AB - Temporal and spatial patterns of St. Louis encephalitis (SLE) virus transmission were compared at permanent study areas in the southern San Joaquin Valley during years with low (1988 and 1990) and elevated (1989) viral activity. During 1989 and 1990, virus appeared first at sentinel chicken flocks exhibiting low to moderate seroconversion rates at the end of the previous season. This finding, and the early season seroconversion of sentinel chickens at a marsh habitat on 5 March and 2 April 1990, circumstantially indicated that SLE virus may have overwintered on the valley during the winters of 1988-1989 and 1989-1990. The mechanism of overwintering was not elucidated further, because virus could not be isolated from overwintering adult mosquitoes or from immatures collected during the spring. An outbreak of 26 confirmed SLE cases occurred in 1989 during a drought year (rainfall 50% of normal) and followed a spring with elevated temperatures (1.7-3.4 degrees C above normal) and Culex tarsalis Coquillett abundance. Cx. tarsalis was the primary vector, being most abundant during the virus amplification period in early summer and most frequently infected (70 SLE virus positive pools/329 tested). SLE virus also was detected in Culex quinquefasciatus Say (14/65) and Cx. stigmatosoma Dyar (1/4); however, both species were distributed focally and increased in abundance only after widespread seroconversions had occurred in sentinel chickens. Increased virus activity during 1989 was not accompanied by marked changes in vector susceptibility or in SLE virus infectivity for mosquitoes. Decreased virus activity in the Bakersfield area during 1990 could not be attributed to immunity in passeriform birds, because a small seroprevalence survey indicated that few adult birds had antibodies to SLE virus. PMID- 1625297 TI - Vector competence of Aedes hendersoni (Diptera: Culicidae) for La Crosse virus: lack of impaired function in virus-infected salivary glands and enhanced virus transmission by sporozoite-infected mosquitoes. AB - Previous research has shown Aedes hendersoni Cockerell to be an incompetent vector of La Crosse (LAC) virus because of a salivary gland escape (SGE) barrier; that is, the salivary glands are infected but the mosquito fails to transmit the virus orally. Intradermal probing behavior and ability to locate blood were studied in infected mosquitoes as indicators of salivary gland impairment to determine if the SGE barrier was due to virus-induced pathology of the salivary glands. No evidence of salivary gland impairment as a result of virus infection was detected in infected Ae. hendersoni. This was also true for Aedes triseriatus (Say), a competent vector of LAC virus, which was used as a control. However, coinfection of Ae. hendersoni with Plasmodium gallinaceum and LAC virus dramatically increased virus transmission (72 versus 8%), whereas transmission by coinfected Ae. triseriatus was not significantly affected. Possible causes for the SGE barrier in Ae. hendersoni are discussed. PMID- 1625298 TI - Biosynthesis of trypsinlike and chymotrypsinlike enzymes in immature Lutzomyia anthophora (Diptera: Psychodidae). AB - The biosynthesis of trypsinlike and chymotrypsinlike enzymes was followed in the four instars and pupa of Lutzomyia anthophora Addis. A 32-fold increase in the biosynthesis of trypsinlike enzymes was observed from the first to the fourth instar. Trypsinlike and chymotrypsinlike isozymes were also synthesized by pupae 1-8 d old. Similarly, a 29-fold increase in the biosynthesis of chymotrypsinlike isozymes also was observed from first to fourth instars. Several different [1,3 3H]DIP trypsinlike and chymotrypsinlike derivatives of first to fourth instars and pupae (1 and 8 d old) were studied using polyacrylamide gel electrophoresis and fluorography. PMID- 1625299 TI - First isolation of Borrelia burgdorferi in southern California. AB - The Lyme disease spirochete, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner, was isolated from the blood of a dusky-footed wood rat, Neotoma fuscipes Baird, in the San Bernardino Mountains of southern California. Antigenic, protein, and molecular analyses demonstrated that the isolate varied slightly from most isolates of B. burgdorferi from northern California and was clearly distinct from other species of Borrelia that are endemic to the state. This is the first reported isolate of B. burgdorferi from southern California and demonstrates that the Lyme disease spirochete is enzootic in mountains near the major human population center of the state. PMID- 1625300 TI - Ecological studies of adult Ixodes scapularis in central Mississippi: questing activity in relation to time of year, vegetation type, and meteorologic conditions. AB - Adult Ixodes scapularis Say were collected weekly during two fall-winter-spring seasons from 1989 to 1991 to assess their temporal and spatial distribution as well as the effects of several meteorologic parameters on questing activity. Collections were made in three 0.4-ha sites in central Mississippi by flagging vegetation with a white flannel cloth. Adult I. scapularis were collected from 25 October through 11 April during the 1989-1990 season and 24 October-1 April in the 1990-1991 season. Peak I. scapularis questing activity occurred on 5 February and 4 February during the two seasons, respectively. Ticks were collected most often at approximately 20 degrees C but seven were collected on a day when the temperature was 6.9 degrees C. Ticks were clustered within the study sites and not evenly distributed. Most I. scapularis were collected from Ligustrum sinense and Chasmanthium sessiliflorum at a height of 31-40 cm. Statistical analyses of the meteorologic factors that affect questing activity are presented and discussed. PMID- 1625301 TI - Ectoparasitic mites (Acari) of sympatric Brazilian free-tailed bats and big brown bats in Alabama. AB - Seven species of mites were recovered from 133 Brazilian free-tailed bats, Tadarida brasiliensis, and 94 big brown bats, Eptesicus fuscus, from February through November 1990 in colonies that shared roosting space in east-central Alabama. The macronyssid Chiroptonyssus robustipes (Ewing) was the most common mite on T. brasiliensis (964 mites, 87% of bats infested) and on E. fuscus (109 mites, 29% of bats infested). However, C. rubustipes normally is a specific parasite of T. brasiliensis. The macronyssids Steatonyssus ceratognathus (Ewing) and S. occidentalis (Ewing) were recovered from both species of bats in low numbers. S. ceratognathus is not a typical parasite of either species of bat, but S. occidentalis normally is specific to E. fuscus. Predictably, S. occidentalis was most frequently collected from E. fuscus (16 mites, 9% of bats infested), but two specimens were recovered from T. brasiliensis. Five specimens of the laelapid Androlaelaps casalis (Berlese) (a mite that is frequently associated with rodents) and one specimen of the myobiid mite Ewingana (Doreyana) longa (Ewing) (a specific ectoparasite of T. brasiliensis) were also recovered from T. brasiliensis. Singletons of the rosensteiniids Mydopholeus sp. and Nycteriglyphites pennsylvanicus Fain, Lukoschus & Whitaker were the only additional mites collected from E. fuscus; both of these mites have previously been collected from bats or their guano but are recorded here from Alabama for the first time. With respect to ectoparasite cross-infestations, E. fuscus appears to be at greater risk from sharing roots with T. brasiliensis. This is highlighted by the comparatively large numbers of C. robustipes that occurred on E. fuscus and the low numbers of S. occidentalis on T. brasiliensis. Although mites were the only arthropods recovered from bats in this study, a separate survey in 1991 revealed that the bat bug Cimex adjunctus Barber infested some other colonies of T. brasiliensis and E. fuscus in Alabama. PMID- 1625302 TI - Inability of Ixodes cookei and Amblyomma americanum nymphs (Acari: Ixodidae) to transmit Borrelia burgdorferi. AB - The vector competency of Ixodes cookei Packard and Amblyomma americanum (L.) for Borrelia burgdorferi was studied using Syrian hamsters. Ixodes dammini Spielman, Clifford, Piesman & Corwin were used as controls. Darkfield and immunofluorescent examinations of midgut diverticula revealed B. burgdorferi spirochetes in 32 of 36 (88.9%) I. dammini larvae, 5 of 36 (13.9%) I. cookei larvae, and 7 of 36 (19.4%) A. americanum larvae within 48 h after feeding on infected Syrian hamsters. B. burgdorferi were also observed in the midguts of 94 of 107 (87.8%) I. dammini nymphs that developed from the fed larvae. However, none of 30 I. cookei nymphs was positive for spirochetes and only 1 of 60 (1.7%) A. americanum nymphs was found positive for B. burgdorferi. Nymphs of each tick species, reared from larvae that had fed on infected hamsters, were allowed to feed on uninfected hamsters to determine their ability to transmit B. burgdorferi. Transmission was demonstrated only by I. dammini nymphs. PMID- 1625303 TI - Population dynamics of adult Culex mosquitoes (Diptera: Culicidae) along the Kern River, Kern County, California, in 1990. AB - The temporal and spatial abundance, dispersal, survivorship, and density of Culex tarsalis Coquillett and Cx. quinquefasciatus Say populations were studied in riparian, agricultural, and residential habitats along the Kern River bed during the drought year of 1990. The temporal abundance of both species was related to cotton agricultural practices and peaked during intensive irrigation after cultivation was terminated in July. Cx. tarsalis peaked in abundance 2 wk earlier than Cx. quinquefasciatus, perhaps because of the advantage of autogenous oviposition, which shortened generation time. Although host-seeking females of both species were most abundant in the riparian habitat, more Cx. quinquefasciatus than Cx. tarsalis were collected in the residential habitat. Marked females released within the riparian habitat were recaptured most frequently within 1 km of the release point; however, flights as far as 12.6 km were documented within the 180-km2 study area. On average, marked Cx. quinquefasciatus dispersed farther and more rapidly than Cx. tarsalis and were recaptured more frequently within the residential habitat. Survivorship, estimated horizontally from the female recapture rate, ranged from 0.60 in May to 0.79 in July for Cx. tarsalis and from 0.74 in September to 0.84 in July for Cx. quinquefasciatus. The estimation of survivorship vertically from the parity rate was complicated by elevated autogeny rates in Cx. tarsalis and by the low parity rate in Cx. quinquefasciatus. Cx. tarsalis population density ranged from 125 females per km2 in May to 65,500 per km2 in August, and was well correlated with relative abundance. Collectively, these ecological data indicated that Cx. tarsalis may be important in disseminating arboviruses within the riparian habitat, but that Cx. quinquefasciatus may be important secondarily by disseminating virus from the riparian habitat to the adjacent residential habitat. PMID- 1625304 TI - Effectiveness of an aerial application of carbaryl in controlling Ixodes dammini (Acari: Ixodidae) adults in a high-use recreational area in New Jersey. AB - Lyme disease risk reduction through the control of the principal tick vector, Ixodes dammini Spielman, Clifford, Piesman & Corwin, has become a major issue facing public health agencies in many endemic states. Where large tracts of land are involved, established methods of I. dammini control are impractical. An aerial application of carbaryl directed against fall populations of I. dammini adults resulted in 93.8% control after 96 h. Control persisted through the following spring. The usefulness of aerial applications may be limited to areas where logistic constraints obviate the use of conventional ground applications. PMID- 1625305 TI - Biosynthesis and metabolism of juvenile hormone III from methyl farnesoate by exposed corpora allata of Lutzomyia anthophora. AB - The in-vitro biosynthesis of [12-3H] juvenile hormone (JH) III by exposed corpora allata (CA) of teneral, sugar-fed, and blood-fed female Lutzomyia anthophora (Addis) was followed by incubating the CA for 4 h with [12-3H]methyl farnesoate. Synthesis of [12-3H]H III was determined by C18 reversed-phase high-pressure liquid chromatography (HPLC) and preparative gas chromatography. The rate of synthesis of JH III by teneral females was 5.6 fmol/h per CA. The CA of 1-d-old females synthesized 17 fmol/h per CA, whereas 3-d-old females synthesized 5.4 fmol/h per CA. The rate of synthesis of JH III 4 h after the blood meal increased to 17.3 fmol/h per CA and then declined to reach a minimum of 1.6 fmol/h per CA at 30 h before increasing again to reach 21.6 fmol/h per CA at 96 h. The concentration of methyl farnesoate in the tissue culture medium during incubation of CA from sugar- and blood-fed females was compared with the rate of synthesis of JH III and its metabolites diol-acid, diol, acid, and bisepoxide. The rate of synthesis of JH III and its metabolites from methyl farnesoate indicated a steady state equilibrium of synthesis and metabolism of JH III by the exposed CA. The rapid increase in JH III synthesis immediately after the blood meal confirmed that in sand flies, like mosquitoes, there is an increase in the rate of synthesis of JH III immediately after the female takes blood. The role of the hormone in vitellogenin biosynthesis is also discussed. PMID- 1625306 TI - New species of the genus Parichoronyssus (Acari: Macronyssidae) on Tonatia evotis (Chiroptera: Phyllostomidae) in southeastern Mexico. AB - The new species Parichoronyssus radovskyi was found on the bat Tonatia evotis in Quintana Roo and Chiapas, Mexico. The female, male, and protonymph are described and illustrated. PMID- 1625307 TI - Facultative myiasis by Megaselia sp. (Diptera: Phoridae) in Texas: a case report. AB - Facultative myiasis caused by larval Megaselia sp. is reported in a human in Texas. On two occasions during 24 h, the youth experienced a "crawling sensation deep in [his] throat" which caused him to cough, expelling a living Megaselia sp. larva. The site of the infestation was presumed to be the sinuses or upper respiratory tract. The symptoms resolved upon expulsion of the larvae, and no additional complications were observed in the patient. PMID- 1625308 TI - Efficient laboratory maintenance of blood-feeding mesostigmatid mites (Acari). AB - A technique is described for colonizing hematophagous mesostigmatid (= gamasid) mites under laboratory conditions. The apparatus consisted of a 473-ml (1 pint) Mason jar with sterilized surgical gauze and corrugated card placed inside on the bottom; these functioned as absorbent and mite bedding materials, respectively. A suckling mouse was placed onto the surgical gauze for 2-24 h to provide a food source for the mites. Stickem adhesive was smeared along the inside neck of the jar, which had a tight-fitting but ventilated screw-cap lid. The apparatus rested in a petri dish filled with water. This system provided excellent containment of the mites. PMID- 1625309 TI - Indoor and outdoor host-seeking rhythms of Anopheles albitarsis (Diptera: Culicidae) in Trinidad, West Indies. AB - The diel host-seeking periodicity of Anopheles (Nyssorhynchus) albitarsis Lynch Arribalzaga (sensu latu) was monitored on humans during a period of 6 mo in Frederick Settlement, County Caroni, Trinidad, West Indies. Similar abundances and periodicities were recorded at indoor and outdoor sites, with peak host seeking occurring at 1900 hours. Only 78 An. albitarsis females were collected resting indoors, indicating that most females rest outdoors and, therefore, may escape contact with residual insecticides applied on wall surfaces. PMID- 1625310 TI - New perspectives in giardiasis. PMID- 1625311 TI - Production of enterotoxin and cytotoxin in Campylobacter jejuni strains isolated in Costa Rica. AB - The production of toxins by 79 strains of Campylobacter jejuni isolated in Costa Rica from children with campylobacter-induced diarrhoea (44 strains) and from chickens (35 strains) was studied. An enterotoxic effect giving a rounding of mouse adrenocortical tumour (Y1) cells, which could be neutralised with antitoxin against Escherichia coli heat-labile enterotoxin, was detected in supernates from 16 (62%) of 26 strains from children with watery diarrhoea, in 5 (28%) of 18 strains from children with bloody or inflammatory diarrhoea, and in 12 (34%) of the 35 strains from chickens. Cytotoxic effects in human lung fibroblasts (MRC 5), African Green monkey kidney (Vero) cells and human cervical carcinoma (HeLa) cells were observed in none of the 26 strains from children with watery diarrhoea, in 2 (11%) of the 18 strains from children with bloody or inflammatory diarrhoea, and in 6 (17%) of the 35 strains from chickens. The simultaneous production of enterotoxin and cytotoxin was detected in four strains. The cytotoxic effect, which was most prominent in cells freshly seeded at a low density, appeared as a lethal rounding of the cells. Fibroblasts were more sensitive than epithelial cells. The effects of the supernates were inactivated by heating at 100 degrees C for 10 min and decreased after 1 week at 4 degrees C. The production of toxins was lost after storage of the strains for one year at 70 degrees C. PMID- 1625312 TI - Killing of alpha-haemolytic and non-haemolytic Escherichia coli strains in human serum and polymorphonuclear leucocytes. AB - The role of alpha-haemolysin (AH) in the resistance of Escherichia coli strains, isolated from patients with extra-intestinal diseases or diarrhoea, to the bactericidal activity of human serum and intracellular killing in polymorphonuclear leucocytes (PMNL) was investigated in vitro. Sets of alpha haemolytic and non-haemolytic E. coli strains and sets of isogenic E. coli strains, which included wild-type alpha-haemolytic strains and derived strains with a reduced production of AH, were used. Compared with non-haemolytic strains, alpha-haemolytic strains were significantly more resistant to the bactericidal activity of 10% and 100% human serum and to intracellular killing in PMNL. Higher resistance to serum killing and to intracellular killing in PMNL was also found in wild-type alpha-haemolytic E. coli than in isogenic bacteria with reduced production of AH. These results provide evidence that production of AH in E. coli strains counteracts both the bactericidal activity of serum and intracellular killing in PMNL. PMID- 1625313 TI - Factors that influence the interaction of Campylobacter jejuni with cultured mammalian cells. AB - Although Campylobacter jejuni is now recognised as a common enteric pathogen, the mechanisms by which this organism produces enteritis remain ill-defined. It has been proposed that its abilities to adhere to and enter epithelial cells represent properties essential to virulence. However, the characteristics of these interactions and factors that may influence the association of C. jejuni with epithelial cells are incompletely described. We have determined that the ability of C. jejuni to bind to epithelial cell lines in vitro is significantly affected by the growth temperature and growth stage of the bacteria, but not by growth-medium composition. Binding of C. jejuni to cultured cells is not affected by temperature or phylogenetic origin of the target cell, and exhibits a non uniform or patchy distribution. In contrast, internalisation is markedly diminished at low temperature, appears to involve active invagination of the target cell membrane via pseudopod formation, and is maximal when cells of human origin are employed. PMID- 1625314 TI - Fibronectin binding of Lactobacillus species isolated from women with and without bacterial vaginosis. AB - Lactobacilli isolated from the vaginas of healthy women (39 strains) and from the vaginal discharge of women with bacterial vaginosis (15 strains) were investigated for their binding to 125I-fibronectin. Nine of the 54 strains bound fibronectin at pH 7.2. The binding capacity of these nine strains was about the same as that observed with Staphylococcus aureas Cowan 1. The binding was specific; an excess of unlabelled fibronectin or its amino-terminal 29-kDa fragment effectively competed for binding, whereas bovine serum albumin, human IgG and orosomucoid did not. Incubation of lactobacilli with fibronectin for different periods revealed a time-dependent increase in binding. Lowering the pH to 4.0 increased the binding capacity of all of the lactobacilli tested; binding occurred with strains that had previously failed to bind at pH 7.2. The increased binding of lactobacilli to fibronectin at a low pH may play a role in the maintenance of the ecological balance of the vagina. PMID- 1625315 TI - Cytopathic effect of Haemophilus ducreyi for human foreskin cell culture. AB - An explant adult foreskin cell culture (FS2-3) was compared with human lung carcinoma cell culture (A549) with regard to the ability of Haemophilus ducreyi to produce a cytopathic effect. The survival of H. ducreyi for up to 26 days in FS2-3 cells was far greater than in any previously described in-vitro culture system. H. ducreyi survived for up to 7 days in A549 cells. The H. ducreyi cells grew and formed "fungal-like" microcolonies on the eukaryotic monolayer. Portions of the microcolonies remained attached despite extensive washing. Transmission electronmicroscopy indicated that, at 48 h after infection, the H. ducreyi cells did not penetrate the FS2-3 cells but they were closely associated with them; there was only a 2-5 nm gap between the H. ducreyi cell wall and the FS2-3 membrane. The virulent H. ducreyi strains RO18 and 35,000 produced a cytopathic effect on FS2-3 cells that did not appear to be due to a soluble toxin. These strains did not produce any CPE on A549 cells. H. influenzae and the avirulent H. ducreyi strain CIP542, inoculated in the same concentration and incubated for the same length of time, did not produce CPE on FS2-3 cells. This study demonstrated that the use of FS2-3 foreskin cell culture provided an in-vitro approach for evaluating the cytopathic effect of virulent H. ducreyi whereby, unlike in other in-vitro systems, viability of the micro-organism could be readily maintained. PMID- 1625316 TI - An analysis of lectin agglutination as a means of sub-dividing gonococcal serovars. AB - Sixteen lectins were examined for their ability to agglutinate 298 strains of Neisseria gonorrhoeae. Seven lectins failed to agglutinate any of the strains; the remaining nine lectins gave 22 different agglutination patterns. The 298 strains were divided into 14 serovars with a single panel of monoclonal antibody typing reagents; lectin agglutination subdivided these into 57 serovar/lectin patterns. A combination of two monoclonal antibody serotyping panels divided the strains into 32 serovar combinations; lectin agglutination further subdivided these into 79 serovar/lectin patterns. There was no correlation between lectin pattern and serovar. Lectin agglutination is a simple supplementary typing method and could be particularly useful in micro-epidemiological studies. PMID- 1625317 TI - Classification of oral pigmented anaerobic bacilli by pyrolysis mass spectrometry and biochemical tests. AB - Clinical (66) and reference (5) strains of pigmented gram-negative anaerobic bacilli, identified as Prevotella intermedia (47), Pr. melaninogenica (1), Pr. corpora (8), Porphyromonas asaccharolyticus (12), P. endodontalis (1) and P. gingivalis (2), were examined by pyrolysis mass spectrometry (PMS) and in conventional tests. Numerical classification based on conventional test reaction patterns (CTRPs) resolved five clusters, four comprising strains identified as Pr. intermedia, Pr. corpora, Pr. melaninogenica, and P. gingivalis respectively, and one comprising strains identified as P. asaccharolyticus and P. endodontalis. Numerical classification based on PMS showed a similar division, with decreasing homogeneity of chemical composition in the order Pr. intermedia, Pr. corpora, P. asaccharolyticus, which agreed with the order of homogeneity in CTRPs. PMS clusters corresponding to the genus Porphyromonas were clearly distinct from those of the genus Prevotella. PMS and CTRP classification disagreed on cluster membership for six strains. PMS identification from blind challenge sets was in agreement with conventional identification for 64 of 67 strains. PMID- 1625318 TI - Radiochemical assay to measure the biofilm produced by coagulase-negative staphylococci on solid surfaces and its use to quantitate the effects of various antibacterial compounds on the formation of the biofilm. AB - A firmly adherent mass of slime plus organisms (biofilm) accumulates on the sides of culture tubes when some strains of coagulase-negative staphylococci are grown in a chemically-defined medium containing [14C]glucose. This mass was washed (to remove labelled medium) and then counted after adding scintillation fluid. Organisms from the liquid culture were also washed and counted to check that [14C]glucose had been utilised to label the bacteria. Nine strains were examined in this way, and the results were compared with those obtained with four older techniques for recognising slime production or adherent bacteria. The new method is quick, and has advantages of reproducibility and good discrimination between strains; there was a 15-fold difference in counts in the biofilm between slime producing and non-producing strains respectively. With the new radiolabel assay, the effects of several antibacterial compounds on the build-up of the biofilm were investigated with four slime-producing strains. Tunicamycin, chloramphenicol and 5-fluorouracil, at levels below their minimum growth-inhibitory concentrations, each greatly diminished biofilm formation; several other drugs had less effect. PMID- 1625319 TI - Characterisation of hospital isolates of Moraxella (Branhamella) catarrhalis by SDS-PAGE of whole-cell proteins, immunoblotting and restriction-endonuclease analysis. AB - Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of whole cell proteins (WCP), immunoblot analysis and DNA restriction-endonuclease analysis (REA) were applied as potential typing methods to 31 clinically significant strains of Moraxella (Branhamella) catarrhalis, five of which came from a suspected outbreak of nosocomial infection in a respiratory-diseases ward. Twelve of 31 isolates were placed in four groups, each of which contained strains indistinguishable by the three typing techniques used. Each of a further two groups contained two strains, and they were similar by at least one technique; the remaining 15 strains were unique by all three methods. Four of five strains from the suspected outbreak were indistinguishable by SDS-PAGE of WCP, immunoblotting and REA. Results show that SDS-PAGE of WCP, immunoblotting and REA are suitable techniques for characterising M. catarrhalis and that there is a considerable degree of strain heterogeneity. Nosocomial infection with M. catarrhalis may be relatively common and further epidemiological studies with a combination of typing techniques are indicated. PMID- 1625320 TI - Cytotoxicity of Bacillus piliformis. AB - Seven isolates of B. piliformis, the agent of Tyzzer's disease, obtained from various host species, were examined for cytotoxic activity by incubating culture filtrates on BRL 3A rat-hepatocyte and 3T3 mouse-fibroblast cell lines. One isolate exhibited cytopathic effects on BRL 3A cells, but not on 3T3 cells. Three other isolates were strongly cytotoxic for 3T3 cells but only slightly so for BRL 3A cells. The remaining three isolates showed no cytotoxicity for either cell line. The cytotoxic products were greater than 100 kDa in mol. wt, thermolabile, and partly destroyed by trypsin treatment. The data show that some B. piliformis isolates produce cytotoxic proteins, which may contribute to the pathogenesis of Tyzzer's disease. PMID- 1625321 TI - Plasmid profiles of "Campylobacter upsaliensis" isolated from blood cultures and stools of paediatric patients. AB - Seventy-three clinical isolates of "Campylobacter upsaliensis" were screened for the presence of plasmids. Plasmid bands were found in 68 (93%) isolates, from which 14 plasmid types were identified. Type 5 was found only in blood-culture isolates, whereas types 7-14 were found only in faecal isolates. Plasmid-free isolates and the other plasmid profiles were present in both faecal and blood isolates. The reproducibility of these profiles was largely dependent on the method of plasmid isolation. The chloroform-phenol lysis method was the most efficient and reliable method of preparing plasmid DNA for plasmid profile analysis. The success of this method may be largely attributable to two factors: (1) the efficacy of cell lysis was independent of either an alkaline agent or of heat; (2) the inactivation of nucleases by the utilisation of chloroform-phenol to lyse the cells. Furthermore, this method of plasmid DNA preparation is ideally suited for use on clinical isolates, especially when rapid plasmid profile analysis may be required. PMID- 1625322 TI - Phospholipid dependence of rat liver microsomal acyl:CoA synthetase and acyl CoA:1-acyl-sn-glycero-3-phosphocholine O-acyltransferase. AB - Investigations were performed on the influence of the phospholipid composition and physicochemical properties of the rat liver microsomal membranes on acyl-CoA synthetase and acyl-CoA:1-acyl-sn-glycero-3-phosphocholine O-acyltransferase activities. The phospholipid composition of the membranes was modified by incubation with different phospholipids in the presence of lipid transfer proteins or by partial delipidation with exogenous phospholipase C and subsequent enrichment with phospholipids. The results indicated that the incorporation of phosphatidylglycerol, phosphatidylserine and phosphatidylethanolamine induced a marked activation of acyl-CoA synthetase for both substrates used--palmitic and oleic acids. Sphingomyelin occurred as specific inhibitor for this activity especially for palmitic acid. Palmitoyl-CoA: and oleoyl-CoA: 1-acyl-sn-glycero-3 phosphocholine acyltransferase activities were found to depend on the physical state of the membrane lipids. The alterations in the membrane physical state were estimated using two different fluorescent probes--1,6-diphenyl-1,3,5-hexatriene and pyrene. In all cases of membrane fluidization this activity was elevated. On the contrary, in more rigid membranes obtained by incorporation of sphingomyelin and dipalmitoylphosphatidylcholine, acyltransferase activity was reduced for both palmitoyl-CoA and oleoyl-CoA. We suggest a certain similarity in the way of regulation of membrane-bound acyltransferase and phospholipase A2 which both participate in the deacylation-reacylation cycle. PMID- 1625323 TI - Purification and characterization of the apical plasma membrane of the rat pancreatic acinar cell. AB - A method is described for the rapid purification of the apical plasma membrane from the rat pancreatic acinar cell. It makes use of wheat germ agglutinin affinity chromatography to selectively bind vesicles with N-acetyl glucosamine present at their surface. Particular conditions (150 mM NaCl) had then to be used to keep membrane vesicles in the coveted orientation, i.e. as right-side-out vesicles. Due to its specific apical location in many epithelial cells, gamma glutamyltranspeptidase was chosen to monitor the purification procedure. The final fraction was enriched in gamma-glutamyltranspeptidase by a factor of 75 relative to the homogenate. Na,K-ATPase, a strict basolateral membrane marker, was not detectable in the fraction. No membranes originating from other compartments, more particularly expected from zymogen granules, or from other cell types, did contaminate the preparation. As expected for an epithelial cell apical plasmalemma, lipid composition showed a very high ratio of glycolipids (37.5%). The absence of membrane-bound GP-2, and the exceptionally high specific activity of gamma-glutamyltranspeptidase suggest that the apical membrane would not be made up by the exocytosis of secretory granule, but instead by the fusion of specialized secretory vesicles very likely originating from the constitutive secretory pathway. In conclusion, this report describes a method of obtaining a fraction highly enriched in the secretory apex of the pancreatic exocrine cell that would be directly involved in exocytosis with zymogen granules and also in local anion transport. PMID- 1625326 TI - Michigan's black dental heritage. PMID- 1625324 TI - Role of Lys 558 and Lys 869 in substrate and inhibitor binding to the murine band 3 protein: a study of the effects of site-directed mutagenesis of the band 3 protein expressed in the oocytes of Xenopus laevis. AB - The effect of mutation of either Lys 558 or Lys 869 or both on mouse erythroid band 3 protein (AE1)-mediated 36Cl- efflux and its inhibition by pyridoxal 5 phosphate (P5-P), DNDS and H2DIDS were studied. Regardless of the mutation, band 3 was always capable of executing Cl- self-exchange. P5-P (5 mM, pH 7.6) produced irreversible inhibition in the wild type (KK) and in the mutant in which Lys 558 (NK) or Lys 869 (KM) had been replaced by asparagine (N) or methionine (M), respectively. However, when both residues were replaced, mutant (NM), irreversible inhibition could no longer be achieved. This shows that P5-P is capable of producing inhibition with either one of the lysine residues, 558 or 869. Inhibition by DNDS changed dramatically upon mutation. The Ki app increased from 6.0 microM in the wild type (KK) to 23 microM in the mutant NK, to 73 microM in the mutant KM and to 474 microM in the double mutant NM. The Km value for activation of the transport system by varying the substrate concentration by isosmotic substitution of Cl- with SO4(2-) decreased from 42 mM in the wild type (KK) to 11.3 mM in the mutant NM. The results show that both Lys 558 and Lys 869 are involved in the maintenance of the structure of the overlapping binding sites for stilbene disulfonates and the substrate Cl-. In the double mutant NM, H2DIDS is no longer able to produce irreversible inhibition at pH 7.6. This is evidently related to the replacement of Lys 558 (pK 8.2) by Asn 558 in this mutant (see Bartel, D., Lepke, S., Layh-Schmitt, G., Legrum, B., Passow, H., 1989. EMBO J. 8:3601-3609). However, at pH 9.5, some irreversible inhibition could still be observed. This suggests that the other lysine residue (pK 10.8) that is known to be involved in covalent binding with the second isothiocyanate group of H2DIDS is still present, and hence, not identical to Lys 869, which had been substituted by a methionine residue. However, this result remains inconclusive since after mutagenesis, the H2DIDS may produce inhibition at a site that is not normally involved in H2DIDS binding. PMID- 1625325 TI - Block of the sheep cardiac sarcoplasmic reticulum Ca(2+)-release channel by tetra alkyl ammonium cations. AB - The purified ryanodine receptor channel of the sheep cardiac muscle sarcoplasmic reticulum (SR) membrane functions as a calcium-activated cation-selective channel under voltage-clamp conditions following reconstitution into planar phospholipid bilayers. We have investigated the effects of the tetra-alkyl ammonium (TAA) cations, (CnH2n+1)4N+ and the trimethyl ammonium cations, ethyltrimethyl ammonium and propyltrimethyl ammonium, on potassium conductance through the receptor channel. Small TAA cations (n = 1-3) and the trimethyl ammonium derivatives act as asymmetric, voltage-dependent blockers of potassium current. Quantitative analysis of the voltage dependence of block indicates that the conduction pathway of the sheep cardiac SR ryanodine receptor channel contains two distinct sites for the interaction of these small organic cations. Sites are located at approximately 50% for tetramethyl ammonium (TMA+) and 90% for tetraethyl ammonium (TEA+) and tetrapropyl ammonium (TPrA+) of the voltage drop across the channel from the cytosolic face of the protein. The chemical substitution of an ethyl or propyl group for one of the methyl groups in TMA+ increases the voltage dependence of block to a level similar to that of TEA+ and TPrA+. The zero voltage dissociation constant (Kb(0)) falls with the increasing number of methyl and methylene groups for those blockers acting 90% of the way across the voltage drop. This is interpreted as suggesting a hydrophobic binding site at this point in the conduction pathway. The degree of block increases as the concentration of small TAA cations is raised. The concentration dependence of tetraethyl ammonium block indicates that the cation interacts with a single site within the conduction pathway with a Km of 9.8 +/- 1.7 mM (mean +/- SD) at 40 mV. Larger TAA cations (n = 4-5) do not induce voltage-dependent block of potassium current of the form seen with the smaller TAA cations. These data support the contention that the sheep cardiac SR ryanodine receptor channel may be occupied by at most one ion at a time and suggest that a large proportion of the voltage drop falls over a relatively wide region of the conduction pathway. PMID- 1625327 TI - Automated endodontics: current concepts. PMID- 1625328 TI - Preventing transmission of hepatitis B. PMID- 1625329 TI - Clinically versus laboratory photocured facings. AB - Acrylic and composite resin facings may fracture or become detached from the metal framework. Insufficient retention, abrasion and trauma are among the causes of these phenomena. Clinical and laboratory techniques have been developed to fabricate facings by means of light-curing composite systems such as the Dentacolor (Kulzer, Inc.) system. The effect of different polishing methods, obtained in both techniques using the same material, was studied with SEM on samples. Finishing and polishing procedures were accomplished using fine finishing diamonds, diamond burs and sof-lex discs. Smooth and lustrous surfaces were obtained with finishing discs, in contrast to techniques using other finishing instruments. Little or no difference in surface texture was observed between samples finished by clinical and those finished by laboratory techniques. PMID- 1625330 TI - Internal management of the implant practice. PMID- 1625331 TI - What is peri-implantitis and how do we prevent and treat it? PMID- 1625332 TI - The technical procedure for the edentulous mandibular overdenture. Simplified procedure for fabrication of an implant overdenture. PMID- 1625333 TI - The key to compliance: MIOSHA requirements for employee training. PMID- 1625334 TI - Guided tissue bone generation. PMID- 1625335 TI - X-ray stereomicroscopy: high resolution 3-D imaging of human spermatozoa in aqueous suspension with natural contrast. PMID- 1625336 TI - An improved cryo-jet freezing method. AB - A new cryo-jet freezing apparatus is described that is easy to use and gives good results using a propane-butene mixture (3:1). Our use of the freezer in the study of mouse spinal cord explant cultures is discussed. At the tissue surface, the quality of tissue preservation from freezing, followed by freeze substitution, rivals that of conventional electron microscopic methods. Certain intracellular structures are better visualized using our methods. There is no evidence of the tissue being distorted by the cryogen jet when the freezer is operated correctly. A new freeze substitution device is also discussed. PMID- 1625337 TI - Coping processes as mediators of the relationship between hardiness and health. AB - Hardiness has been hypothesized to moderate the impact of stress on health by influencing coping responses, but little attention has been focused upon these associations. This study examined the relationship among hardiness, coping, and illness while attending to recent criticisms of the hardiness literature including the potential overlap with neuroticism, whether hardiness is a unitary construct, and the predominant use of male samples. Hardiness was found to be positively related to adaptive coping variables and negatively related to maladaptive coping variables. Problem-focused, support-seeking, and avoidant coping were found to mediate the hardiness-illness relationship. Although these hardiness-coping relationships were partially independent of the influence of neuroticism, the relationship of both coping and hardiness with self-reported illness appeared to result from the common influence of neuroticism. Consistent with previous research, the commitment and control components correlated most consistently with coping variables, and predicted hardiness effects were most consistently demonstrated for males. PMID- 1625338 TI - Dimensions of anger-hostility and cardiovascular reactivity in provoked and angered men. AB - This study investigated the relationship between two dimensions of anger hostility--the expression of anger-hostility and the experience of anger hostility--and cardiovascular reactivity in provoked and angered men. A serial subtraction task was administered to 41 male undergraduates who were provoked and angered. A measure of the expression of anger-hostility correlated positively and significantly with systolic and diastolic blood pressure (BP) reactivity. There were no significant correlations between a measure of the experience of anger hostility and cardiovascular reactivity. The two types of anger-hostility were also found to relate differentially to life-style variables that have been identified as risk factors for coronary heart disease (CHD), with only the expression of anger-hostility showing positive relationships with these life style CHD risk factors. These findings are discussed within the context of a similar differential relationship between the two dimensions of anger-hostility and CAD and CHD. Finally, significant negative relationships were obtained between the experience of anger-hostility and resting BP and heart rate levels. These findings are discussed within the context of other data suggesting that trait anxiety-neuroticism may have protective properties. PMID- 1625339 TI - Anger and impatience/irritability in patients of low socioeconomic status with acute coronary heart disease. AB - This case-control study examines the relationship between anger and impatience/irritability and acute coronary heart disease (CHD) in middle-aged men of low socioeconomic status (SES). Subjects included patients with myocardial infarction (MI) (N = 31) or unstable angina (AP) (N = 26), who were compared with hospital controls (N = 26). In separate multivariate analyses for each anger scale, MI was associated with Anger-Out and Impatience/Irritability, particularly in the subgroup of patients who did not have a previous MI. The same factors were associated with AP, but only when this acute ischemic event was not preceded by a MI. No relationship was found between Trait-Anger and Anger-In and either acute ischemic outcome. The results indicate that particularly overt behavioral expression of anger is related to CHD in lower SES patients and that there is similarity in the behavioral factors associated with acute CHD between low- and high-SES men. PMID- 1625341 TI - A psychophysiological evaluation of female urethral syndrome: evidence for a muscular abnormality. AB - This is a preliminary investigation into a recently defined urological disorder occurring in a subgroup of women with "urethral syndrome" suggestive of pelvic floor muscular (PFM) dysfunction. Symptoms include straining to void, urgency, frequency, hesitation, incontinence and/or retention, and subpubic pain. Finding neither bladder nor urological abnormalities, urologists may consider these women emotionally unstable without organic cause for their symptoms. However, their distress may be a consequence rather than a cause of their voiding problems. Sixteen female urological patients were matched with 16 asymptomatic controls to investigate PFM functioning, psychological status, and symptomatology. Results showed heterogeneity of symptomatology and little elevation of depression or anxiety when comparing patients with controls. Hypotheses of muscular abnormality were confirmed. Patients evidence poor control over testing and relaxing PFM, elevations of PFM activity under various conditions, and chronic pain as a prominent symptom. Treatment approaches specifically designed to address PFM dysfunction are discussed. PMID- 1625342 TI - Primary care physicians in Mississippi: implications for rural health care. AB - Despite a 24% increase in Mississippi primary care physicians during the 1980s, rural areas of the state continue to be underserved with 39 of 82 counties classified as health manpower shortage areas for primary medical care. Utilizing 1980 and 1990 census data and reports from the Mississippi State Department of Health, primary care physician manpower was analyzed to determine where growth and trends occurred. Most of the primary care physician growth occurred in ten populous counties, with family physicians and general practitioners continuing to provide most of the care in the lesser populated counties. Public and private entities are exploring new and innovative methods of delivering health care to rural areas which recognize the changing professional and lifestyle expectations of today's physicians. Multispecialty primary care group practices need to be promoted and innovative financial arrangements provided. Educational systems need to recruit students from rural areas and provide more training experiences in rural areas. PMID- 1625340 TI - Psychological and physiological predictors of lipids in black males. AB - The association between lipids and both psychological and physiological measures were examined in this study of healthy black males. The results revealed that certain psychological measures, namely, State and Trait Curiosity and Trait Anger, explained a significant proportion of the variance in high-density lipoproteins (HDL), low-density lipoproteins (LDL), and triglycerides. Although psychological factors accounted for a significant proportion of the variance in lipids (29% for HDL, 25% for LDL, 64% for LDL/HDL, 29% for triglyceride), the amount of explained variance was significantly increased by the inclusion of both psychological and physiological variables in the regression equation. However, neither of the psychological variables explained any of the variance for total cholesterol when physiological variables were included in the regression analysis. The overall pattern of the findings suggests that black males who are at increased risk for elevated lipid levels may be identified by their level of mental vigilance, the frequency at which their anger is experienced, and the presence of other traditional risk factors. PMID- 1625343 TI - Graduate follow-up in the University of Mississippi family practice residency program. AB - Practice profiles in 120 University Medical Center Department of Family Medicine residency graduates were assessed by questionnaire and follow-up telephone calls. Physician credentials, career satisfaction, and evaluation of residency training were also addressed. Findings include some preferences for partnership or group practice settings and practices in communities of less than 25,000. Eighty percent of graduates remain in Mississippi, and most are satisfied with their careers and the residency training they received. Changing patterns in areas such as obstetrical care provided and Medicare/Medicaid acceptance suggest new surveys may be needed to provide the department with information that will assist in meeting its goals. PMID- 1625344 TI - Report of the AMA Council on Ethical and Judicial Affairs: reporting impaired, incompetent, or unethical colleagues. PMID- 1625345 TI - Feeling like a 'real doctor' again. PMID- 1625346 TI - Bioluminescent measurement in single cardiomyocytes of sudden cytosolic ATP depletion coincident with rigor. AB - The sequence of events that leads to irreversible injury of the ischaemic myocardium is poorly understood but it is axiomatic that lack of oxygen will impair regeneration of ATP. In the globally-ischaemic heart a contracture develops which is independent of raised cytoplasmic free Ca2+ and which has been attributed to activation of actomyosin by nucleotide-free actomyosin cross bridges ('rigor complexes') which form at low ATP concentrations. Single, metabolically-poisoned or anoxic cardiomyocytes show comparable behaviour, shortening before a significant rise in cytoplasmic free Ca2+ occurs. To explain the close temporal relationship that exists between cell shortening and the onset of the free Ca2+ rise we have predicted that, during myocyte shortening, a precipitous fall in cytosolic ATP concentration occurs, the result of rigor complexes activating myosin ATPase, which then perturbs ionic homeostasis. Here we show, by means of continuous measurements of cytosolic ATP using firefly luciferase microinjected into single, isolated cardiomyocytes, that cell shortening coincides with an abrupt fall in cytosolic ATP. PMID- 1625347 TI - Prolonged propionyl-L-carnitine pre-treatment of rabbit: biochemical, hemodynamic and electrophysiological effects on myocardium. AB - Recently it has been reported that prolonged treatment with propionyl-L carnitine, a carnitine derivative, results in a positive inotropic effect. To gain further insight into its mode of action, we pre-treated 253 rabbits for up to 10 days with daily doses of 1 mmol/kg propionyl-L-carnitine or L-carnitine intraperitoneally, using saline-treated animals as control. Twenty-four hours after the last injection, we isolated papillary muscles for electrophysiological investigations. Whole hearts were used in perfusion experiments for biochemical and hemodynamic measurements. In addition, mitochondria were harvested from these hearts for the analysis of their function. Plasma and cardiac levels of free carnitine, along with plasma short-chain acylcarnitines, increased at least two fold after treatment with carnitine or its propionyl-ester, with concomitant rises in tissue long-chain acylcarnitine and long-chain acyl-CoA. At the time of animal sacrifice, treatment did not increase plasma or tissue propionyl-L carnitine content. The studies carried out with perfused hearts and isolated mitochondria failed to show an effect of propionyl-L-carnitine pre-treatment on high-energy phosphate metabolism or respiration. Papillary muscles from animals, treated for 10 days, showed a lengthening of the action potential duration from 63 +/- 4 to 102 +/- 6 ms (P less than 0.001) at -10 mV. Perfused hearts from these rabbits displayed positive inotropy, as indicated by an improved pressure development at higher ventricular filling volumes, e.g., from 39 +/- 4 to 60 +/- 3 mmHg (P less than 0.05) at 3.6 ml. Pre-treatment with L-carnitine or saline failed to affect the electrophysiological and hemodynamic variables. Thus, prolonged treatment of rabbits with propionyl-L-carnitine, but not with L carnitine, improved contractility and lengthened action potential duration in isolated muscle preparations. PMID- 1625348 TI - Evidence for malonyl-CoA-sensitive carnitine acyl-CoA transferase activity in sarcoplasmic reticulum of canine heart. AB - The formation of palmitoylcarnitine is catalyzed by carnitine palmitoyl transferase (CPT-I) and this catalysis is the first committed step in beta oxidation. The malonyl-CoA-inhibited isoform appears to be distinct from latent (CPT-II) activity, which is localized to the matrix side of the mitochondrial inner membrane. Sarcoplasmic reticulum from canine cardiac muscle was fractionated on a discontinuous sucrose density gradient into three major bands, all of which contained Ca(2+)-ATPase activity. Only the fraction that banded at a concentration of 38% surcrose was slightly contaminated by mitochondria. Peroxisomal uricase was low or absent in fractionated SR. All sarcoplasmic reticulum fractions contained malonyl-CoA-sensitive medium- (COT) and long-chain (CPT) carnitine acyltransferase activities. CPT activity decreased in sarcoplasmic reticulum when Triton X-100 was present. Carnitine acyltransferase activities were inactivated by preincubating the sarcoplasmic reticulum with the sulfhydryl reagent, 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB). In contrast, mitochondrial CPT-II activity was stable in the presence of DTNB and activated by Triton X-100. Western blots of mitochondria and sarcoplasmic reticulum fractions showed that the mitochondrial fractions reacted with antibody to mitochondrial CPT-II but not with SR protein when both were added at comparable specific activities. The data suggest that cardiac SR contains a unique malonyl-CoA sensitive isoform of CPT, and that synthesis of acylcarnitine may occur in the microenvironment of Ca2+ transport, where the extent of production of acylcarnitine is controlled by cardiac acetyl-CoA carboxylase activity. PMID- 1625349 TI - Increase in myofilament separation in the "stunned" myocardium. AB - This study explores the effects of ischemic reperfusion injury on the radial separation distance between thick and thin myofilaments. The left anterior descending coronary artery was occluded for 5 mins and reperfused for 10 mins twelve times repetitively in 6 dogs. At the end of a final 90 min reperfusion period, the hearts were fixed by perfusion with glutaraldehyde, and subepicardial and subendocardial tissue from both normal and ischemic areas were prepared for transmission electron microscopy. Quantitative analysis of inter-filament distance (IFD) was performed on micrographs of transverse sections. The center-to center IFD was calculated from the numerical density of thick filaments at the A band level using a hexagonal array conversion formula. Sarcomere length was measured on micrographs of longitudinal sections. The results showed that center to-center thick IFD in the stunned subendocardium was 43.9 +/- 0.8 nm which was significantly greater than the control distance of 40.6 +/- 0.4 nm (P less than 0.001) from normal zone tissue. Thick IFD in the subepicardium was also significantly different: 43.4 +/- 0.6 nm in the stunned tissue as compared with 39.0 +/- 0.7 nm in the non-ischemic tissue (P less than 0.001). Sarcomere length in the normally perfused subendocardium was 2.01 +/- 0.07 micron and was increased to 2.20 +/- 0.08 micron in the stunned subendocardium (P less than 0.005). Sarcomere length in the normal and the stunned subepicardium was also different: 2.02 +/- 0.04 vs. 2.10 +/- 0.09 micron (P less than 0.005). The significant increase in spatial separation between the contractile filaments may affect optimal cross-bridge force generation at the molecular level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625350 TI - Myocardial adenosine formation during hypoxia: effects of ecto-5'-nucleotidase inhibition. AB - Release of adenosine and AMP into epicardial fluid and coronary venous effluent of isovolumic guinea-pig hearts was examined during normoxic (95% O2) and hypoxic (30% O2) perfusion with and without the ecto-5'-nucleotidase inhibitor alpha,beta methylene adenosine diphosphate (AOPCP)*. Normoxic epicardial and venous adenosine levels were 221 +/- 27 and 67 +/- 11 nM, respectively, in untreated hearts. During 15 min of hypoxia, epicardial and venous adenosine levels increased in a phasic manner, reaching maximal values of 498 +/- 32 and 441 +/- 43 nM, respectively, during the initial 5 min of hypoxia. Epicardial and venous adenosine levels then declined slightly during the subsequent 10 min to 332 +/- 33 and 224 +/- 34 nM, respectively. Infusion of 50 microM AOPCP significantly reduced venous adenosine levels during normoxia (less than 50% of control), but was without effect on normoxic epicardial adenosine. Epicardial and venous adenosine levels increased during hypoxia with AOPCP but the increases were lower than those for untreated hypoxic hearts. Epicardial and venous adenosine levels recovered to baseline levels following 30 min of reoxygenation in both groups. Epicardial and venous AMP levels were elevated by AOPCP treatment during normoxia and hypoxia. Coronary vascular resistance decreased during hypoxia but the decline in resistance was less in AOPCP treated hearts. It is concluded that whereas basal interstitial adenosine levels appear to be independent of ecto-5' nucleotidase activity, the hypoxic increase in interstitial adenosine is partially derived from an AOPCP sensitive ecto-5'-nucleotidase. Venous adenosine appears to be significantly dependent on ecto-5'-nucleotidase activity during normoxia and hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625351 TI - The effects of aspartate and 2-oxoglutarate upon glycolytic energy metabolites and mechanical recovery following global ischaemia in isolated rat hearts. AB - The hypothesis that aspartate and 2-oxoglutarate might help to relieve the inhibition of glycolysis during global myocardial ischaemia and improve post ischaemic mechanical recovery was tested in isolated rat hearts. The hearts were attached to a lumped parameter model of the rat vascular impedance and initially perfused in the working mode with buffered Krebs-Henseleit solution containing 10.1 mmol/l glucose, with or without 3.3 mmol/l of aspartate and 3.3 mmol/l of 2 oxoglutarate, prior to imposing global ischaemia for 5, 10 or 15 mins. The addition of aspartate and 2-oxoglutarate improved the preservation of tissue CP after 5 mins of ischaemia and of ATP after 10 mins of ischaemia. The total adenine nucleotide pool was higher in the supplemented hearts after all three periods of ischaemia. Dihydroxyacetone phosphate, alanine, succinate and lactate accumulated during ischaemia, but the dihydroxyacetone phosphate accumulation was reduced while the alanine and succinate concentrations were increased by the addition of aspartate and 2-oxoglutarate to the perfusate. These observations lend support to the hypothesis that ischaemia arrests glycolysis at the glyceraldehyde phosphate dehydrogenase step due to a lack of oxidised nicotinamide adenine dinucleotide. Increasing the substrate concentrations of aspartate and 2-oxoglutarate may permit glycolysis to proceed for longer into the period of ischaemia by stimulating an additional pathway for nicotinamide adenine dinucleotide reoxidation. Small improvements in mechanical recovery were associated with the metabolic changes. PMID- 1625352 TI - Heterogeneous distribution of fatty acid-binding protein in the hearts of Wistar Kyoto and spontaneously hypertensive rats. AB - In the present study we investigated the concentrations of cardiac cytoplasmic fatty acid-binding protein (H-FABPc) in various regions of the left and right ventricles of both Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). To this end, the ventricles of six WKY and six SHR hearts were cut in three slices, which were further dissected in one right ventricular piece and ten left ventricular pieces (five inner layer and five outer layer pieces). After homogenisation. H-FABPc was assessed using an Enzyme Linked Immuno Sorbent Assay (ELISA) of the sandwich type. It was found that, when expressed per gram wet tissue, the overall concentration of H-FABPc tended to be lower in SHR than in WKY hearts (874 +/- 53 micrograms/g and 955 +/- 51 micrograms/g, respectively; 0.1 less than P less than 0.2, means +/- S.E.M. for n = 6 animals in each group). However, due to a 30-35% higher ventricular heart mass in SHR than in WKY, the total H-FABPc content per heart turned out to be about 20% higher in SHR than in WKY rats. No concentration differences could be detected between right and left ventricles in WKY and SHR but a marked difference between the outer layer and the inner layer of the left ventricular wall was monitored in both groups. In general, the concentration in the outer layer was 5-15% higher than in the corresponding inner layer. These differences reached the level of significance (P less than 0.05) in regions close to the basis of the heart. PMID- 1625353 TI - Why do ischemic and hypoxic myocardium lose potassium? PMID- 1625354 TI - Response of the cardiovascular system to stress. Annual meeting of the International Society for Heart Research (American Section). Burlington, Vermont, 17-20 June 1992. Abstracts. PMID- 1625355 TI - Congestive heart failure in the elderly--echocardiographic insights. AB - One hundred and seventy-two patients (110 were greater than or equal to 65 years and 62 were less than 65 years) with congestive heart failure (CHF) were prospectively evaluated to determine various pathophysiologic mechanisms of CHF. The incidence of CHF with normal left ventricular (LV) systolic function was higher in elderly (30% vs 12%, p less than 0.05). Of the 110 elderly patients, LV systolic function was impaired in 77. Fifty-five patients had LV dilatation without increased wall thickness, and the clinical diagnosis was "dilated cardiomyopathy in the elderly". Twenty-two patients had hypertrophied LV and a high incidence of hypertension, and they were diagnosed as "hypertensive heart failure" due to contractile dysfunction. On the contrary, the remaining 33 patients did not have impaired LV contractile function. Thirteen patients lacking LV hypertrophy had enlarged atria. CHF was induced by reduced chamber compliance called "the stiff heart syndrome". Twenty patients had hypertrophied LV and a high incidence of hypertension. They were diagnosed as having "hypertensive hypertrophic cardiomyopathy of the elderly" and abnormalities of diastolic function accounted for the CHF. Since echocardiography can easily and accurately diagnose the pathophysiologic mechanism of CHF, an increased awareness of its occurrence in the elderly and use of echocardiography would reduce diagnostic and therapeutic errors. PMID- 1625356 TI - Intermediate-term results of balloon valvuloplasty for isolated and complicated pulmonary valve stenosis. AB - The purpose of this study is to report our experience regarding the acute and intermediate-term results of balloon pulmonary valvuloplasty (BPV) in various types of congenital pulmonary valve stenosis. METHODS AND RESULTS: Twenty-four consecutive patients with a median age of 6.6 years (ranging from 1 month to 24 years old) underwent BPV between January 1988 and September 1991. These patients were divided into 2 groups; Group 1 consisting of 13 patients with isolated pulmonary valve stenosis, and Group 2 consisting of 11 patients with complicated pulmonary valve stenosis (supravalvular, subvalvular, valved conduit and post right ventricular outflow reconstruction). Mean peak systolic pressure gradients from the right ventricle to the pulmonary artery were as follows: In group 1, 48 +/- 21 (mean +/- SD) mmHg before BPV, 18 +/- 8 mmHg immediately after BPV and 13 +/- 5 mmHg at the longest follow-up based on catheterization or Doppler echocardiographic studies. The gradients in group 2 were 65 +/- 28 mmHg before BPV, 46 +/- 25 mmHg immediately after BPV and 47 +/- 21 mmHg at the longest follow-up. CONCLUSIONS: BPV provides both acute and intermediate-term gradient relief in patients with isolated pulmonary valve stenosis. In complicated pulmonary valve stenosis, on the other hand, the effect of BPV was unsatisfactory and appears to depend on the mechanism of associated obstruction. Therefore accurate evaluation of the anatomy of associated obstruction in the pulmonary valve region is needed to determine that BPV is indicated. PMID- 1625357 TI - Pulmonary arterial flow-pressure characteristics in dogs--effects of hypoxia and nitroglycerin. AB - To investigate the effects of hypoxia and nitroglycerin on pulmonary vascular tone, multipoint mean pulmonary arterial flow-pressure (Q-P relationship) plots were constructed by producing stepwise increments of pulmonary flow with a roller pump installed in a right ventricle-pulmonary artery shunt in 12 mongrel dogs under pentobarbital sodium anesthesia. The normal Q-P relationship was convex to the pressure axis when pulmonary flow was 0-0.2 L/min, but it became linear when pulmonary flow was over 0.2 L/min. The slopes and pressure intercepts extrapolated (RAPI) from linear regression fits to the linear parts of the Q-P relationship were determined to compare the effects of hypoxia and nitroglycerin on pulmonary vascular tone. Hypoxic ventilation (FIO2: 0.1) increased the slope from 8.3 +/- 3.3 to 12.5 +/- 3.6 mmHg/L (p less than 0.01), with no significant effect on PAPI. Nitroglycerin (1 microgram/min/kg as a continuous infusion) decreased the slope from 8.9 +/- 4.4 to 5.8 +/- 2.6 mmHg/L (p less than 0.05), again with no significant effect on PAPI. The results suggest that hypoxia and nitroglycerin, respectively, increased and decreased incremental pulmonary vascular resistance upstream to the site of pulmonary vascular closure. PMID- 1625358 TI - Torsades de pointes in patients with electrical alternans of T-U wave without change in QRS complex. PMID- 1625359 TI - 55th Annual Scientific Session of the Japanese Circulation Society. Kyoto, March 31, 1991. PMID- 1625360 TI - Evaluation of arterial wall histological and physical characteristics using intravascular echography. AB - Using a high-frequency ultrasound intravascular imaging system we evaluated the intravascular echo image by comparing it with histological findings in 57 arterial segments of 17 autopsy cases. Moreover, in 8 dogs we estimated the arterial elastic property by observing the change of the arterial section accompanying a reduction of arterial pressure due to hemorrhage (H) or nifedipine infusion (N). The characteristics of the intravascular echograms were as follows: 1) In a normal artery the arterial wall consisted of the inner high echoic, the medial low echoic and the outer high echoic layers. 2) In an aged artery the fibrous thickened intima was seen as the low echo layer giving an echo about the same as that of the normal media, and the intensity of the echo from the degenerated media was lower than that of the normal media. 3) In atheroma the echo intensity of the elastic fiber-rich region was higher than that of the surrounding region, while the calcified region showed as a brighter echo with outer echo free space due to shadowing. We measured the arterial radius, area and circumferential length on the intravascular echo image and calculated the arterial wall tension-circumferential length and the pressure-arterial area relationships. By analysing each relation, we obtained the stiffness and compliance parameters, respectively. The stiffness parameter with N was lower than that with H [(1.5 +/- 0.5) x 10(-2) vs (2.8 +/- 0.9) x 10(-2)] and the compliance parameter with N was higher than that with H (0.92 +/- 0.28 vs. 0.46 +/- 0.12).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625361 TI - Intravascular ultrasound imaging--in vitro and vivo validation. AB - Intravascular ultrasound imaging is a new technique for visualizing arterial structures. The purpose of this study was twofold; first, to assess the ability of this intravascular ultrasound catheter to generate cross-sectional images of human artery segments in vitro and second, to determine the reliability of intravascular ultrasound technique in the evaluation of human arteries in vivo. For the vitro study, ultrasound images of the arteries were presented as a two dimensional, 360 degrees display of vessel cross-section perpendicular to the long-axis of the probe. The ultrasound scanning provided an accurate description with high resolution of lumen structure and lumen-intima interface in all vessel specimens. There was a good correlation between the planimetric luminal area on the ultrasound images and the area obtained from histologic images (r = 0.92). There was also a good correlation in the plaque thickness between ultrasound and histological examination (r = 0.88). In the in vivo study, the ultrasound catheter was easily introduced, readily manipulated, and images were successfully obtained in all patients. No untoward effects were noted during manipulation of the catheter. There was a good correlation in the arterial dimension between ultrasound and angiographic measurements (r = 0.93). Thus, intravascular ultrasound imaging appears to be useful for characterizing and quantitating arterial lesions. PMID- 1625362 TI - Intravascular ultrasound imaging in human peripheral and coronary arteries in vivo. AB - To determine the feasibility of intravascular ultrasound imaging in vivo, a miniaturized high frequency transducer catheter was introduced into human peripheral (n = 10) and coronary (n = 4) arteries. Cross-sectional ultrasound images were obtained from iliofemoral arteries in 10 patients using a 20 MHz transducer catheter (1.2 mm in diameter) and from coronary arteries in 4 patients using a 30 MHz transducer catheter 5 French size (Fr) following successful coronary angioplasty. Ultrasound images obtained from peripheral arteries showed a three-layered appearance (echo-reflective intima, echo-lucent media and echo reflective adventitia) in the normal arteries. In diseased arteries, the location, amount and extent of atheromatous plaque were clearly documented. The arterial diameters measured by ultrasound closely correlated with the measurements by angiography (r = 0.91) in the peripheral arteries. Coronary angiograms obtained following balloon angioplasty revealed smooth edges at the dilatation sites without significant narrowing in all patients. However, a significant amount of residual atheromatous plaque was clearly observed on the ultrasound images at the previously dilated sites. Coronary dissection, which was identified as an echo-lucent area behind the plaque, was noted in 2 patients. Ultrasound images also revealed the presence of calcium in the plaque which was unrecognized on the angiograms in 3 patients. In addition, direct measurement of the lumen cross-sectional area was possible on the ultrasound images.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625363 TI - The effectiveness of coronary angioscopy in detecting intraluminal pathologic changes. AB - We have evaluated the feasibility of percutaneous transluminal coronary angioscopy for detecting intraluminal pathological changes as a diagnostic tool, and investigated the pathogenesis of two acute coronary disorders, acute myocardial infarction and unstable angina. Twelve patients with an acute coronary disorder and 20 patients who underwent percutaneous transluminal coronary angioplasty were selected for this comparison between the diagnostic accuracy of angioscopy and arteriography. One hundred and thirty patients were investigated by angioscopy as follows in order to investigate the pathogenesis of their acute coronary disorders: 22 within 8 h of onset acute myocardial infarction; 28 from one day to 2 months since onset recent myocardial infarction; 37 with an old myocardial infarction; 26 with unstable angina; and 23 with stable angina. Our results have indicated thrombi were detected more frequently by angioscopy than by arteriography (p less than 0.01). Also, thrombi, intimal irregularities, and xanthomatous atheromas were observed more frequently in patients with acute myocardial infarction, recent myocardial infarction, and unstable angina. It is concluded that coronary angioscopy is a much more sensitive method for detecting intraluminal changes, and that a thrombus overlying a rupture in the lining of plaque plays a major role in an acute coronary disorders, and that the fragile, lipid-rich gruel atheroma may precede its rupture. PMID- 1625364 TI - Advances in transesophageal echocardiography for the evaluation of atherosclerotic lesions in thoracic aorta--the effects of hypertension, hypercholesterolemia, and aging on atherosclerotic lesions. AB - We assessed atherosclerotic lesions in the thoracic aorta in 166 consecutive patients (aged 56 +/- 13 years) by transesophageal echocardiography, and investigated the influences of hypertension, hypercholesterolemia and age on the prevalence of such lesions. Satisfactory images were obtained of all the thoracic aorta, except for a small part of the ascending aorta, by use of a biplane transesophageal probe. We defined atherosclerotic lesions as increased echogenicity of the intima (intimal thickening), raised plaque, calcification, ulceration, or aneurysms. Lesions were observed in 97 patients (58%). The incidence of lesions in patients with hypertension (81%) or hypercholesterolemia (80%) was significantly greater than in those without both conditions (37%, p less than 0.005). The incidence of lesions was significantly increased among patients over 60 years old compared with that in patients under 60 (76% vs 42%, p less than 0.005). Patients without either hypertension or hypercholesterolemia showed a marked increase in the incidence of lesions with age (16% at less than 60 yrs vs. 67% at greater than 60 yrs), and no significant influence of these conditions on the incidence of lesions was found in patients over 60. We conclude that hypertension and hypercholesterolemia might be important risk factors for the development of atherosclerotic lesions in the thoracic aorta in relatively younger patients. Age appears to become a more important determinant of such lesions in Japanese patients over 60 years old irrespective of blood pressure and serum cholesterol levels. PMID- 1625365 TI - Assessment of myocardial viability by using newly developed myocardial SPECT imaging. AB - Thallium myocardial imaging has been widely available for the detection of myocardial ischemia and assessment of myocardial viability in coronary artery diseases. However, myocardial imaging using SPECT and gamma-emitting radiopharmaceuticals has been developed for accurate evaluation of myocardial infarction and ischemia. The present study was undertaken to clinically evaluate myocardial necrosis, metabolism and sympathetic nerve activity. In this study, myocardial fatty acid metabolism was assessed using 123I-BMIPP, myocardial sympathetic neural activity was assessed using 123I-MIBG and myocardial necrosis was assessed using 111-In-antimyosin Fab. Dual energy SPECT using these new agents and thallium gives precise characterization of myocardial viability in coronary artery disease. PMID- 1625366 TI - Positron emission tomography--usefulness in assessing myocardial viability. AB - Positron emission tomography (PET) using N-13 ammonia and F-18 fluorodeoxyglucose (FDG) has been used to evaluate myocardial viability in comparison with thallium 201 single photon emission computed tomography (SPECT), and left ventricular wall motion in comparison with contrast ventriculography. Forty patients with anterior myocardial infarction underwent stress and delayed resting perfusion imaging using Tl-201 SPECT and ammonia PET, a glucose metabolism study using FDG PET, and wall motion assessment with left ventriculography. Out of a total of 600 segments of left ventricular imaging, SPECT demonstrated 197 fixed perfusion defects, 99 with redistribution on delayed imaging and 304 normal segments. Of 197 segments with fixed defects, 24 (12%) were normal and 71 (36%) ischemic according to PET criteria. Nineteen of 28 with infarction and all of 12 with non-Q wave infarction showed a viable myocardium. Left ventricular wall motion was significantly better in patients with normal PET findings compared with those with ischemia or scar on PET. Post-PTCA PET revealed improved ammonia PET in 6 of 11 patients but reduced FDG uptake was noted only in 3. These data suggests that Tl-201 SPECT significantly underestimates myocardial viability and that PET imaging is a promising tool for assessing the presence of salvaged myocardium. PMID- 1625367 TI - In vivo 31P nuclear magnetic resonance spectroscopy in patients with old myocardial infarction. AB - To assess the usefulness of in vivo 31P nuclear magnetic resonance (NMR) spectroscopy, we investigated spectra from the myocardium in 6 patients with old Q-wave infarction (QMI), 6 with old non-Q-wave infarction (NQMI) and 9 controls by ECG-gated depth-resolved surface-coil spectroscopy. External hexamethylphosphoric triamide (HMPT) was used to quantify the signal intensities. Left ventricular weight in the region of interest (LVW) was estimated from 1H magnetic resonance images. The extent score by 201Tl scintigraphy was determined in 3 QMI and 4 NQMI patients. No significant differences were found among the 3 groups in peak area ratios of 31P NMR spectra to phosphocreatine (PCr) or adenosine triphosphate (ATP). Compared with controls, significant reductions were observed in values for the peak areas of PCr normalized by the standard HMPT (PCr/HMPT) or by both HMPT and LVW (PCr/HMPT/LVW) for QMI patients (p less than 0.05), and in ATP/HMPT and ATP/HMPT/LVW for QMI and NQMI patients (p less than 0.01). There was a significant negative correlation between ATP/HMPT and the 201Tl scintigraphy extent score (p less than 0.05). These findings suggest that in vivo 31P NMR spectroscopy can detect high-energy phosphate reduction in the infarcted myocardium and may be useful in evaluating myocardial viability. PMID- 1625368 TI - High-energy phosphate metabolism of the myocardium in normal subjects and patients with various cardiomyopathies--the study using ECG gated MR spectroscopy with a localization technique. AB - Nuclear magnetic resonance spectroscopy (MRS) is a new technique for the evaluation of myocardial metabolism. Recently, localized MRS has been clinically available to measure by a non-invasive method the relative concentrations of the high-energy phosphate metabolites in the myocardium. We performed ECG gated P-31 MRS using ISIS (image-selected in vivo spectroscopy) in 15 normal volunteers, 12 patients with hypertrophic cardiomyopathy, 12 with left ventricular hypertrophy, 6 with dilated cardiomyopathy and 11 with specific heart muscle disease. Myocardial peak height ratios of PCr/gamma-ATP, Pi/gamma-ATP and PCr/Pi were measured. Myocardial P-31 MRS demonstrated a significant decrease in the ratio PCr/ATP in patients with hypertrophic cardiomyopathy and specific heart muscle disease as compared with normal subjects, indicating myocardial metabolic disturbance in these patients. The ratio of PCr/ATP in patients with dilated cardiomyopathy did not differ significantly from that of normal subjects. However, exercise MRS revealed a marked decrease of PCr peak in an asymptomatic patient with dilated cardiomyopathy, which may indicate a latent metabolic disturbance in the myocardium of dilated cardiomyopathy. PMID- 1625369 TI - Evaluation of myocardium in ischemic heart disease by ultrafast computed tomography. AB - In this study we evaluated quantitatively the contrast enhancement of the myocardium of 27 patients with infarction and ischemia by ultrafast CT (Imatron C 100) with a scan time of 100 msec. We defined three parameters from the CT numbers of the myocardium and the ventricle in both the early and the late phase (about 4 min) after the injection of non-ionic contrast material; the difference of the CT numbers of myocardium between the early and the late phase (delta CT#), and the ratios of the CT numbers of the myocardium and the ventricular lumen (M/L) in both the early phase and the late phase. The delta CT# for myocardial infarction and severe ischemia were -20 +/- 10HU and -8 +/- 10HU, respectively. These values were significantly lower than the mild ischemic myocardium and normal myocardium (p less than 0.001). The average M/L values for myocardial infarction and ischemia in the early phase were 19 +/- 8% and 16 +/- 6%, respectively. These values were significantly lower than those in normal myocardium (p less than 0.001). The average M/L values for infarction and severe ischemia in the late phase were 90 +/- 18% and 63 +/- 20%, respectively. These M/L were significantly dissociated (p less than 0.001). Our results indicate that with contrast UFCT it is feasible to detect quantitatively the myocardial characteristics of ischemia and infarction. PMID- 1625370 TI - Evaluation of cardiac motion and function by cine magnetic resonance imaging. AB - Cardiac cine magnetic resonance imaging (MRI) was studied to evaluated the cardiac motion and function, and a water-stream phantom study was performed to clarify whether it was possible to quantitatively assess the valvular regurgitation flow by the size of the flow void. In normal subjects, the left ventricular (LV) epicardial apex swung up to the base only a few millimeters, and the mitral annulus ring moved about 14 mm as mean value toward the apex during systole. Those motions of mitral annulus ring may contribute to the left atrial filling. The LV longitudinal shortening and torsions were shown by the tagging method. This tagging method was the best method for estimating cardiac motions. Cardiac cine MRI using software including a modified Simpson's method program and a wall motion analysis program was useful for routine LV volumetry and wall motion analysis because it was a simple and reliable method. Our water-stream phantom studies demonstrated that it might be difficult to perform quantitative evaluation of valvular regurgitation flow by using only the size of the flow void without acquiring information relating to the orifice area. PMID- 1625371 TI - Correlation of alpha activity between the frontal and occipital cortex. AB - A method of modified coherence analysis was applied to the interpretation of EEG differences between the frontal and occipital cortex. This paper discusses a bidirectional communication model for the frontal and occipital cortex. Directed coherence method was used to analyze alpha activities over the scalp. The results show that both in the left and right hemisphere, slow waves in the alpha frequency band had high correlation in the frontal-occipital direction, and fast waves had high correlation in the occipital-frontal direction. It may suggest that the structure of information transmission is different for fast and slow waves of alpha rhythm. PMID- 1625372 TI - Characteristics of TNF alpha- and TNF beta-induced fever in the rabbit. AB - Febrile responses of rabbits to recombinant human tumor necrosis factors alpha (TNF alpha) and beta (TNF beta) were compared. Intravenous (0.1-30 micrograms/kg, I.V.) and intracerebroventricular (0.01-2.5 micrograms/kg, I.C.V.) injection of TNF alpha and TNF beta both caused monophasic and biphasic fevers depending on the dose. The magnitude of fever induced by I.V. and I.C.V. injection of TNF beta was significantly greater than that induced by TNF alpha. Moreover, the second peak of TNF beta-induced biphasic fever was attained more quickly than that of TNF alpha-induced fever. Indomethacin given subcutaneously inhibited the fevers produced by I.V. and I.C.V. injection of TNF alpha and TNF beta. Fever induced either by intravenously injected TNF beta or by intracerebroventricularly injected TNF beta was significantly inhibited by I.C.V. pre-injection of indomethacin. On the other hand, indomethacin given intracerebroventricularly did not affect the fever induced by I.V. injection of TNF alpha or that induced by I.C.V. injection of TNF alpha. These results suggest that TNF alpha and TNF beta act on the brain sites responsible for the activation of prostaglandin synthesis in somewhat different ways. PMID- 1625373 TI - Effects of increased ureteropelvic pressure on fluid and NaCl absorption across the jejunum. AB - The aim of the present study was to elucidate the effects of an increased ureteropelvic pressure (UPP) on the net jejunal fluid, Na+, and Cl- absorption in anesthetized dogs. UPP was changed under hydrostatic pressure with warmed Ringer's solution. At a UPP of 0 mmHg, the net jejunal fluid, Na+, and Cl- absorption were 10.1 +/- 0.5 ml, 2.4 +/- 0.1, and 2.0 +/- 0.1 mEq, and were significantly reduced to 5.9 +/- 0.4 ml, 2.0 +/- 0.1, and 1.6 +/- 0.1 mEq, respectively, by an increase in UPP to 60 mmHg. After lowering the UPP to 0 mmHg, the net absorption recovered to the control values. The same experiments were performed after ipsilateral renal denervation. Ipsilateral renal denervation completely abolished this response. This result suggests that the afferent pathway of this response is the renal nerves. We also assessed the validity of the method using a jejunal loop by examining the effects of repetition of the absorption experiment on the net absorption. The net absorption was not altered by 6 times repetition of the absorption experiment. To determine the collection ratio, phenol red was used in the first and sixth absorption experiments. The collection ratios were 92.2 +/- 1.1 and 90.3 +/- 0.9%, respectively. There was no significant difference in collection ratio between the first and sixth values. This is the first report in which an increased UPP was found to inhibit the net jejunal fluid, Na+, and Cl- absorption. PMID- 1625374 TI - Decreases in catecholamine concentrations of cisternal cerebrospinal fluid and plasma in rats caused by pentobarbital anesthesia. AB - Pentobarbital anesthesia led to a decrease of noradrenaline concentrations of both cisternal cerebrospinal fluid and plasma and adrenaline concentration of plasma with a concomitant decrease in blood pressure in rats. These data suggest that pentobarbital suppresses both central and peripheral noradrenergic nervous activity. PMID- 1625375 TI - Effect of splanchnic nerve stimulation on epinephrine and norepinephrine release from gastrointestinal sympathetic postganglionic endings in the frog. AB - Gastrointestinal vascular perfusates in bullfrogs before and after splanchnic nerve stimulation were collected and analyzed for epinephrine and norepinephrine. Catecholamine in the perfusate before stimulation was predominantly epinephrine. Upon stimulation a marked increase in epinephrine release without any significant change in norepinephrine release was observed in experiments at 8-10 degrees C as well as 16-21 degrees C, showing that in frogs epinephrine is the sympathetic neurotransmitter and that the release of epinephrine is not affected by low temperatures. PMID- 1625376 TI - Systems analysis of the carotid sinus baroreflex system using a sum-of-sinusoidal input. AB - The purpose of the present study was to determine the dynamic characteristics of the carotid sinus baroreflex system (CS) employing systems analysis. In 28 anesthetized and mechanically ventilated dogs with vagotomy, intracarotid sinus pressure (ICSP) was changed artificially. In protocol 1 (n = 7), we estimated the transfer function of the CS by means of a single sinusoidal input (SIN), the Gaussian white-noise input (GWN), and a sum-of-sinusoidal input (SUM). The transfer function of ICSP to systemic arterial pressure (SAP) was second-order delay with an identical corner frequency of 0.025 Hz and damping ratio of 0.7. The steady-state gain estimated using GWN (1.12 +/- 0.13) or SUM (1.13 +/- 0.08) was significantly smaller than SIN (1.69 +/- 0.25). In protocol 2, to find the reason why there was a difference among the estimated steady-state gains, we investigated the effect of ICSP pulsation on the open-loop gain of the CS. The maximum gain of the gain curve was decreased and the operating range was increased significantly with the 2-Hz pulsation. We could simulate the above phenomena by using a model with a nonlinear sigmoidal relationship between ICSP and SAP. The dynamic characteristics of the CS appeared to be changed by pulsation, but this phenomenon was attributable to the sigmoidal nature of the relationship between ICSP and SAP. Pulsation decreases the maximum gain and increases the operating range, which may contribute to stability of the CS and homeostasis of SAP. PMID- 1625377 TI - Response field of cat trigeminal sensory complex neurons responsive to mechanical stimulation of the canine tooth. AB - Response fields of periodontal mechanoreceptive (PM) neurons in the cat's trigeminal sensory complex were examined while mechanical stimulation was applied to the canine tooth in 12 directions on the horizontal plane. Almost all the slowly adapting PM neurons were directionally selective to stimulation, and their response fields had response angles greater than 180 degrees, i.e. broad type. PMID- 1625378 TI - Effects of chronic administration of noradrenaline and glucagon on in vitro brown adipose tissue thermogenesis. AB - The in vitro brown adipose tissue (BAT) oxygen consumption stimulated by noradrenaline (NA) or glucagon (G) was significantly lower in chronically NA treated rats and that of G-treated rats did not differ as compared with that of vehicle-treated control animals. In vitro thermogenic response of BAT in NA treated rats was consistent with that induced by cold acclimation. PMID- 1625379 TI - Evidence of direct activation of adenosine A1 receptor by 5'-adenosine monophosphate in isolated guinea pig atrial myocytes. AB - The electrophysiological effect of 5'-adenosine monophosphate (AMP) was examined in isolated atrial myocytes of guinea pig. Membrane potential and ionic currents were measured by the tight-seal, whole-cell patch-clamp technique. AMP caused the shortening of atrial action potential in a dose-dependent manner. In voltage clamp experiments, AMP (3-10 microM) caused the activation of IKACh as well as the decrease in basal ICa. Prolongation of action potential duration caused by isoproterenol (20 nM) was antagonized by AMP (10 microM). Isoproterenol (20 nM) occasionally caused the sustained rhythmic activity and the subsequent application of AMP (10 microM) terminated it. AOPCP (10 microM), which inhibits 5'-nucleotidase and hence prevents breakdown of AMP, did not significantly attenuate the effect of AMP on shortening action potential. However, the application of adenosine deaminase (1 U/ml), which deaminates adenosine to inosine, partially reversed the shortening of action potential caused by AMP (10 microM). These results indicate that (1) AMP could activate IKACh and decrease basal ICa simultaneously, and antagonize the isoproterenol-stimulated action potential prolongation; and (2) the observed electrophysiological effect of AMP in whole-cell preparation is attributed to AMP per se as well as its degradative product, adenosine. PMID- 1625380 TI - Biphasic change in plasma potassium concentration by mannitol infusion in rats. AB - Changes in plasma Na+([Na+]pl) and K+([K+]pl) concentrations were continuously measured in nephrectomized rats consequent to intravenous infusion of isosmotic mannitol (M group) or sucrose (S group) at 1.6 ml/100 g body wt. for 10 min, and for the following 30 min. The effect of a Ca2+ channel blocker (diltiazem, 0.1 mg/100 g body wt.) was also evaluated. In the S group, [K+]pl decreased during the infusion and rose above the control level after the discontinuance of infusion. In the M group, [K+]pl gradually increased even during the infusion and reached the same level as the S group at the end of the experiment. In both the S and M groups, [Na+]pl decreased, while PaCO2, pH, and HCO3- did not change. The increase in [K+]pl in the M group had two components. The first was a transient component as presented by the difference of [K+]pl between the M and S group. It might be attributable to K+ release from the intracellular space during a regulatory volume decrease consequent to cell swelling induced by isosmotic mannitol infusion. The second component of the increase in [K+]pl after the infusion was observed in both groups, and this increase might be related to the dilution of ions induced by the large amount of infused nonelectrolyte solution. Diltiazem suppressed both of these changes in [K+]pl, suggesting that they are related to Ca2+ channels. The results suggest that increase in [K]pl by isosmotic mannitol infusion is related to the effects of regulatory volume decrease and dilutional effect. PMID- 1625381 TI - Effects of cold acclimation on cold-induced changes in lipid metabolism of rat brown adipose tissue. AB - Effects of acute cold exposure (0 degree C, 12 h) on lipid metabolism of the interscapular brown adipose tissue (BAT) were studied in warm controls (25 degrees C) (WC) and cold-acclimated rats (5 degrees C, 4 weeks) (CA). 1) We confirmed that cold acclimation brought about decreased BAT triglyceride (TG) level and increased BAT phospholipid (PL) level. The indexes of unsaturation, such as unsaturation index and polyunsaturated fatty acids/saturated fatty acids ratio, of bulky fatty acids (FA) (palmitic, stearic, oleic, and linoleic acids) decreased in TG, while those increased in PL. Rare FA (eicosadienoic acid, homo gamma-linoleinic acid, lignoceric acid) level, which were about five times higher in PL than TG in WC, decreased in both TG and PL in CA. 2) Effect of acute cold exposure in WC: The level as well as the amount of TG in BAT was greatly reduced and the indexes of unsaturation in TG-FA increased. The most part of reduced TG (85%) was explained by the bulky FA. Rare FA explained only 1.1% of reduced TG. PL level in BAT did not change, but its amount decreased. The indexes of unsaturation increased in PL-FA. 3) Effect of acute cold exposure in CA: CA was placed in warm temperature of 25 degrees C before cold exposure. In contrast with the cold-reduced TG in WC, either the level or the total amount of TG in BAT did not change, but the indexes of unsaturation in TG-FA decreased. The level as well as the total amount of PL in BAT increased. The arachidonic index and arachidonate in PL-FA decreased, but the indexes of unsaturation did not change. These results indicate as a whole that acute cold exposure as well as cold acclimation influences BAT lipid metabolism in FA compositions as well as amount of TG and PL, suggesting that such changes are related to thermogenic activity of this tissue. PMID- 1625383 TI - [A case of psittacosis with migratory infiltrates]. AB - A 56-year-old man with fever, headache, cough and sputum was admitted to another clinic. Chest X-ray examination revealed infiltrates in the upper lobe of the right lung. Cefem and aminoglycoside therapy was not effective, and the infiltrates migrated from the right upper lobe to the right middle and lower lobes and then to the left lung. He was transferred to our clinic, and laboratory data showed that CRP was 6+; ESR, 119 mm/1 h; WBC, 3000/mm3; and CAR, 512. The tentative diagnosis of atypical pneumonia was based on the positive agglutination test for Legionella pneumophila, and treatment with erythromycin, minocycline and rifampicin resulted in alleviation of symptoms and resolution of the infiltrates in the lungs. Complement fixation titer for Chlamydia was 128 at admission and was elevated to 512 after 2 weeks. Indirect fluorescent antibody for Legionella was negative. Transient liver dysfunction was also observed. PMID- 1625382 TI - Measurements of CO2 diffusivity and buffering capacity in myoglobin solutions. AB - Diffusion processes of CO2 into or out of a thin layer of myoglobin (Mb) solution were followed by pH-sensitive fluorescence of 4-methylumbelliferone. Mb solutions were prepared by dissolving horse heart Mb at 0.1 to 4 mM in a modified Krebs solution containing NaHCO3 of 30 mM. Carbonic anhydrase was added to observe the diffusion-limited pH changes. The PCO2 in the layer were calculated as the numerical solution of a diffusion equation. For the simulation of the observed pH time curves, the PCO2 changes were converted to the pH changes using a linear relation between logPCO2 and pH. The diffusion coefficients of CO2 and HCO3- (DCO2 and DHCO3) were determined as the optimum parameters to fit the calculated pH-time curves to the observed ones. Both the DCO2 and DHCO3 decreased exponentially as the Mb concentration was increased. At a physiological concentration of Mb in cardiomyocytes (0.2 mM) and at 37 degrees C, the DCO2 and DHCO3 values were 9.8 x 10(-5) and 16 x 10(-5) cm2.s-1, respectively. The buffer value (beta) was calculated as the slope of a pH-bicarbonate diagram by measuring the CO2 content and pH of the Mb solutions equilibrated with known PCO2 gases. The beta was found to increase with increasing Mb concentration with a value of 6.2 mEq.l-1.pH-1 at 0.2 mM. PMID- 1625384 TI - [A case of primary antiphospholipid syndrome with fever, pulmonary thromboembolism and endocardial lesion]. AB - A previously healthy 16-year-old girl complaining of fever, hemosputum, chest pain and dyspnea was hospitalized. On admission, physical examination revealed mental confusion, holosystolic heart murmur, and swelling of the left foot. Laboratory investigations showed anemia, leukocytosis, thrombocytopenia, activation of inflammatory reactions, prolongation of PT and APTT, and hypoxia. Antinuclear antibody test was negative. There were no other findings suggestive of collagen diseases such as SLE. Chest X-ray showed consolidation in the left lower lung field and pleural effusion. Echocardiography disclosed a mass lesion in the left atrium in contact with the mitral valve, and mitral regurgitation. No findings indicative of an infectious etiology were present. The patient rapidly improved with high dose corticosteroid and anticoagulant therapy. A venogram of the lower extremity disclosed deep venous thrombosis. A lung ventilation perfusion scan revealed multiple pulmonary thromboemboli. Elevation of anticardiolipin antibody was noted. Based on these findings, the diagnosis of primary antiphospholipid syndrome was made. Further administration of steroid and anticoagulant resulted in decrease of the titer of anticardiolipin antibody. This is the second report of primary antiphospholipid syndrome in Japan. The clinical significance of this disease is also discussed. PMID- 1625385 TI - [A case of bronchocentric granulomatosis presenting as a tumorous shadow on chest X-ray film]. AB - A 57-year-old woman was admitted to our hospital with cough, sputum and abnormal chest X-ray. In summer, 1989, she developed cough which gradually worsened in autumn. In November, the chest X-ray revealed a tumorous shadow in the left suprahilar region. On admission, there were no symptoms of bronchial asthma. Chest X-ray revealed a subpleural tumorous shadow in the left upper lung field. X ray findings suggested that the tumorous shadow in the suprahilar region moved to the left peripheral upper lung field. Left B1+2 orifice obstruction with necrotic tissue was seen on fiberoptic bronchoscopy. Transbronchial biopsies failed to yield specific diagnostic findings, except for bronchitis with exudate containing eosinophils. In February, 1990, she developed hemosputum and left chest pain. Chest X-ray showed consolidation in the left apical lung field. Left upper lobectomy was performed. Histological examination disclosed many granulomas with central necrosis around the bronchi, and aspergillus hyphae were seen. These findings are compatible with bronchocentric granulomatosis without asthma. PMID- 1625386 TI - [Prophylactic effect of ulinastatin on cisplatin-induced renal disorders in lung cancer patients]. AB - In order to determine whether ulinastatin (US) can prevent renal dysfunction due to cisplatin (CDDP) or not, we comparatively studied serum BUN, serum creatinine (Cr), creatinine clearance (Ccr), urine gamma-glutamyl transpeptidase (gamma-GTP) excretion, urine N-acetyl-beta-D-glucosaminidase (NAG) excretion, fractional excretion of Na (FENa) and urine beta 2-microglobulin excretion between one group of 10 patients receiving single treatment with CDDP and another group of 10 patients receiving combination treatment with CDDP+US, in 20 subjects with primary lung cancer. In the US combination treatment group, urine gamma-GTP excretion, urine NAG excretion, and FENa elevation were significantly inhibited. Urine beta 2-microglobulin excretion was inhibited. In summary, US was considered to have a preventive effect against renal toxicity due to CDDP. PMID- 1625387 TI - [A case of intractable hemoptysis due to malignant hemangioendothelioma]. AB - A 65-year-old man who died of respiratory failure due to malignant hemangioendothelioma is reported. He was admitted to our hospital because of intractable hemoptysis. Chest roentgenogram revealed multiple patchy shadows in both lungs, but we could not make a diagnosis by usual clinical examinations including transbronchial lung biopsy. Since the patient's condition became critical, oxygen therapy, anticoagulants and antibiotics were started. In addition, corticosteroid therapy and double filtration plasmapheresis were performed since immunological disorder was suspected because of positive immunological examinations such as antinuclear antibodies and an increase in circulatory immune complexes. There was little response to the treatments and the patient finally died of respiratory failure. At autopsy, multiple tumor nodules were found throughout the lungs and the liver. Metastasis to mediastinal lymph nodes was also discovered. These findings made it impossible to confirm the primary lesion. Microscopy showed proliferation of anastomosing capillaries encasing tumor cells of unknown origin. Silver staining demonstrated capillaries encompassing the atypical cells, suggesting a vascular origin of the tumor. Furthermore, factor VIII related-antigen in the tumor cells was confirmed by the peroxidase-antiperoxidase (PAP) method. The final diagnosis of malignant hemangioendothelioma was made from these histological findings. Malignant hemangioendothelioma is rare, but is an important cause of intractable hemoptysis. PMID- 1625388 TI - [A case of gold-induced pneumonitis showing a positive reaction in the drug lymphocyte stimulation test (DLST) for gold]. AB - A case of acute interstitial pneumonia developing during gold therapy is reported. A 67-year-old female with rheumatoid arthritis for about twenty years who received a total dose of 80 mg of gold thiomalate (Shiosol) for about two months, developed high fever and dry cough. Exertional dyspnea developed and chest roentgenogram showed diffuse small nodular and reticular shadows. RA and RAPA tests were positive. Drug lymphocyte stimulation test (DLST) for Shiosol was positive. The dyspnea resolved on administration of methylprednisolone. Chest roentgenogram and CT-scan showed improvement. A total dose of 80 mg of gold thiomalate, as administered in this case, is the minimum dose previously reported in Japan. It has been recently reported that allergic reaction is the mechanism of gold lung. In the present case, positive DLST indicated the existence of many activated lymphocytes, and was very useful in the diagnosis of gold lung. PMID- 1625389 TI - [A case of plasmacytoma of the ribs with intrathoracic tumors]. AB - A 75-year-old male was admitted because of two tumors, one in the left middle lung field and one in the right upper lung field. Chest CT revealed intrathoracic tumors extending from destroyed ribs. Biopsy specimens of both tumors showed well differentiated plasmacytoma. Retrospective investigation suggested that solitary plasmacytoma of bone (SPB) originating in the left fourth rib had developed into multiple myeloma (MM). Both tumors were treated with doses of 50 Gy irradiation and responded very well. Intrathoracic plasmacytomas have rarely been observed, so we have no established classification or therapy. According to reported cases, we classified intrathoracic plasmacytomas into 5 groups, and consider that treatment with doses of over 40 Gy irradiation was adequate for local control. PMID- 1625390 TI - [A case of diffuse endobronchial infiltration in a patient with non-Hodgkin's lymphoma]. AB - A 38-year-old man with diffuse endobronchial infiltration with non-Hodgkin's lymphoma (NHL) is reported. He was admitted to our hospital on November 1990 because of lymph node swelling. Physical examination on admission revealed left axillary, bilateral cervical and inguinal lymph node swelling. Chest and abdominal CT scan showed para-aorta lymph node swelling, mild splenomegaly and heterogeneous density of the liver, although hilar and mediastinal lymphadenopathy were not found. Microscopic examination of the biopsy specimen obtained from the right inguinal lymph node and liver revealed NHL (B cell lymphoma, diffuse, mixed type). After two courses of chemotherapy, a chest roentgenogram showed bilateral hilar lymphadenopathy and reticular shadows. CT scan demonstrated a thickening of the left main bronchus. Bronchoscopic examination revealed a small submucosal nodule in the left main bronchus on February 1991, from which the biopsy specimen revealed NHL infiltration similar to that of the lymph node. At follow-up bronchoscopic examination, in spite of chemotherapy, scattered NHL infiltration was found in the submucosal space of the left vocal cord, carina and the bifurcation between left upper and lower bronchi. In patients with NHL, endobronchial involvement is rare. In this case, diffuse endobronchial infiltration was not thought to be direct invasion from the lymph node but hematogenous or lymphatic spread to the bronchi. PMID- 1625391 TI - [A case of carcinosarcoma of the lung]. AB - A 78-year-old man was admitted to our hospital with cough and left anterior chest pain. Chest X-ray examination on admission revealed a tumor shadow in the left upper lobe. Malignant tumor cells were observed on histopathological examination of a specimen obtained by bronchoscopic biopsy. Radiotherapy was performed but was not effective, and the patient died of respiratory failure 4 months after admission. Autopsy revealed a 15 cm diameter tumor with marked local invasion tendency without distant metastasis. Microscopically, the tumor consisted partly of squamous cell carcinomas, and partly of fibrosarcomas, composed of spindle cells and osteo-chondrosarcoma. The tumor was therefore diagnosed as carcinosarcoma. Immunohistochemical examination showed positive keratin and EMA staining only in the squamous cell carcinoma component of the tumor. PMID- 1625392 TI - [A case of localized pleural mesothelioma containing a wedge-shaped area of aeration]. AB - A 32-year-old man was admitted to our hospital because of an abnormal shadow on the chest X-ray film, which was detected on mass survey. The chest X-ray film on admission revealed an irregular mass shadow in the pleural layer between the left upper lobe and the lower lobe, and this shadow had a wedge-shaped area of aeration inside it. Needle biopsy under ultrasonography suggested a localized pleural mesothelioma. Surgery to resect the tumor revealed that it was pedunculated and had developed from the pleura of the left S5 segment. The resected specimen showed lung tissue invaginating into the tumor through a concave area of the tumor. The chest X-ray findings of this case are very unusual, and we were unable to find a similar case of localized pleural mesothelioma in the literature. PMID- 1625393 TI - [Clinical aspects of precapillary pulmonary hypertension]. AB - Cor pulmonale is present in 54-64% of patients with respiratory failure (mean PaO2: 52-54 Torr) receiving home oxygen therapy in Japan. This may imply that the development of clinical symptoms of cor pulmonale in the course of the disease more strongly reflects far advanced stage than the presence of respiratory failure. In this paper, clinical data from subjects with various forms of precapillary pulmonary hypertension were analysed with respect to correlation between the prognosis and the pulmonary vascular response to various therapeutic modalities such as acute administration of oxygen, vasodilator drugs, and surgery. The results were as follows: 1) In subjects with COPD, there was a significant correlation between mean pulmonary arterial pressure (PPA) and prognosis. Patients who showed decreased pulmonary vascular resistance (% delta PVR less than -10) after 100% oxygen inhalation had a good prognosis. 2) In subjects with sequelae of pulmonary tuberculosis, there was no apparent correlation between the prognosis and % delta PVR after 100% oxygen inhalation. 3) In subjects with both COPD and sequelae of pulmonary tuberculosis, the lowest value of desaturation during sleep was significantly correlated to the PPA during wake. 4) Analysis of 232 cases with primary pulmonary hypertension revealed the following prognostic factors: PPA, cardiac output, stroke volume index, pulmonary vascular resistance, mixed venous oxygen tension, right atrial pressure, total bilirubin, and total protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625394 TI - [Experimental study on development and lung injury in pneumonia under neutropenic condition]. AB - This study was performed to demonstrate the characteristic findings in pneumonia under neutropenic condition. The results were as follows. 1) After nebulizing Klebsiella pneumonia DT-S strains, the survival rate in the neutropenic mouse group rapidly decreased compared with that of the control group. 2) In the neutropenic state, a rapid decline of survival rate was demonstrated during the initial stage of infection. Bacteremia and endotoxemia developed earlier than in the healthy control group. 3) In neutropenic pneumonia, the neutrophil cell count in BALF was significantly lower than that in usual pneumonia. Consequently, a large number of bacteria grew in the alveolar spaces during the early period after inhalation. Neither inflammatory cell infiltration nor thickening of the alveolar wall was present; however, structural destruction of alveolar and vascular walls was found. 4) These pathological changes were also seen following intratracheal inoculation of some extracellular enzymes of Klebsiella pneumoniae DT-S into rabbit lung. However, no destruction of alveolar walls was observed after nebulizing the killed Klebsiella pneumoniae DT-S. It was suggested that the significant amount of enzymes produced by the bacteria growing in the alveoli caused tissue damage, especially in the neutropenic state. 5) Thus the typical inflammatory changes that occurred in the usual state, were not seen in neutropenic pneumonia, and a large number of bacteria grew in the alveoli. Marked tissue damage was caused by extracellular enzymes produced by bacteria. Consequently, bacteria entered the blood stream and bacteremia and endotoxemia developed. These processes observed in neutropenic pneumonia readily progressed to bacteremia of endotoxemia, which are more severe in this state. PMID- 1625395 TI - [Assessment of alveolar epithelial permeability in progressive systemic sclerosis (PSS) using 99mTc-DTPA (diethylene triamine penta acetate) aerosol inhalation]. AB - To evaluate alveolar epithelial damage in PSS, we studied pulmonary epithelial permeability by measuring the clearance of inhaled 99mTc-DTPA aerosol and performing thin slice CT scan, pulmonary function tests and right heart catheterization in 28 patients with PSS. The 99mTc-DTPA clearance rate (kep value) in PSS was greater than in 11 non-smoking normal subjects (18.2 +/- 7.63 x 10(-3)/min vs. 9.12 +/- 0.77 x 10(-3)/min, p less than 0.01). In PSS, the kep value did not correlate with age, sex, duration of illness, dermal lesions, % vital capacity, or PaO2. In contrast, the kep value showed significant correlations with %DLco (diffusing capacity for carbon monoxide), extent of interstitial lesions evaluated by CT scan (CT score), and mean pulmonary artery pressure. On the other hand, the kep value was high in some patients with normal CT scan and normal %DLco. These findings indicate that pulmonary interstitial lesions in PSS are accompanied by alveolar epithelial damage, and that the clearance of 99mTc-DTPA may be an early predictor of interstitial change. PMID- 1625396 TI - [Analysis of bronchoalveolar lavage fluid in patients before and after bone marrow transplantation]. AB - We analysed BALF cell findings in 9 patients (group A: 5 patients without lung disease after bone marrow transplantation (BMT), group B: 4 patients with lung disease after BMT) before and after BMT. Before BMT, BALF cell findings in group A were almost normal, whereas a relative increase of lymphocytes was seen in group B. Although total cell counts and cell composition in group A changed little after BMT, CD4/CD8 ratios in BALF lymphocytes decreased. In contrast, a relative increase of lymphocytes and neutrophils was seen in group B and there was variation of CD4/CD8 ratios in BALF lymphocytes after BMT. We there studied the BALF lymphocytes of 3 patients in group A and 4 patients in group B after BMT by means of 2-color analysis. Among CD4+ cell populations, CDw 29+ cells were decreased in both groups after BMT. A relative increase of BALF-CD4+ HLA-DR+ cells and CD8+ HLA-DR+ cells was seen in group A, but was not seen in group B. These findings suggest that there is abnormality of local immunity in the lung after BMT. PMID- 1625397 TI - [Ventricular performance during exercise in patients with chronic obstructive pulmonary disease (COPD)]. AB - We assessed ventricular performance during exercise in 16 COPD patients and 8 normal control subjects by means of radionuclide equilibrium angiography using technetium-99m as a tracer. Supine exercise on a bicycle ergometer was performed until symptom-limited exhaustion. Data were accumulated for 300 heart beats at rest and 150 heart beats during exercise. We used the standard voxel count method to calculate the ventricular volumes. Age, FEV1.0%, %VC, PaO2 and PaCO2 of the COPD patients were 63 +/- 8 yr, 46 +/- 11%, 69 +/- 18%, 68 +/- 11 Torr and 44 +/- 7 Torr (mean +/- SD), respectively. Systolic dysfunction of both the left and right ventricles was well confirmed in the present study. In 12 patients who also underwent hemodynamic studies, resting total pulmonary vascular resistance index (TPVRI) and mean pulmonary artery pressure (Ppa) significantly correlated with right ventricular end-systolic volume index (RVESVI) obtained by RI angiography; gamma = 0.769 (p less than 0.01) and gamma = 0.631 (p less than 0.05), respectively. A significant relationship was also observed between left ventricular dysfunction and the degree of hypercapnia. In response to exercise testing, 10 of 16 patients exhibited insufficient augmentation of stroke volume, and both left and right end-diastolic volumes decreased in half of 10 patients. It is suggested that cardiac function may be disturbed by mechanical factors such as pulmonary hyperinflation in COPD patients. PMID- 1625398 TI - [Eosinophil colony stimulating factor production by lymphocytes from patients with bronchial asthma]. AB - To investigate the eosinophilia in patients with bronchial asthma (BA), we examined the release of eosinophil colony stimulating factor (Eo-CSF) from blood mononuclear cells (MNC) and lymphocytes from BA. We also investigated the effect of specific antigens on the release of Eo-CSF to determine its relation to other known Eo-CSFs. 1) Phytohaemagglutinin (PHA) and interleukin (IL)-2 at optimal concentrations stimulated mononuclear cells from BA, and induced Eo-CSF release. In contrast, MNC from normal volunteers released Eo-CSF with only PHA, but did not release Eo-CSF with IL-2. 2) Lymphocytes from BA who were sensitive to house dust mite and Dermatophagoides farinae (D. farinae) antigens responded to specific antigens with Eo-CSF production, but those from normal volunteers did not. 3) The anti-IL-3, anti-IL-5, and anti-granulocyte-macrophage (GM)-CSF antibody inhibited Eo-CSF activity in culture media of lymphocytes from BA. These results indicate that the increase in responsiveness of lymphocytes from BA to specific antigens and cytokines produced by T cells play an important role in the induction of eosinophilia in BA. PMID- 1625399 TI - [Leukocyte migration inhibition test in drug-induced pneumonitis]. AB - The leukocyte migration inhibition test (LMIT) was performed in 8 cases of presumed drug-induced pneumonitis. The drugs involved were amiodarone in 3 cases, methotrexate in 2 cases, and fenofibrate, nadolol, and gold salt, each in one case. The agarose microdroplet technique for photoelectric readings of leukocyte migration inhibition was applied in the presence of a wide range of drug concentrations. LMIT was found to be positive in 6 of the 8 cases (75%). The presence of a positive LMIT indicates the elaboration of leukocyte migration inhibitory factor. These results suggest that cell-mediated immunity may play a role in the pathogenesis of drug-induced pneumonitis and that LMIT may be useful for the detection of causative drugs in patients with this condition. PMID- 1625400 TI - [Content and localization of leukotriene C4 in lung tissue during biphasic allergic bronchoconstriction in the guinea pig]. AB - Leukotriene C4 (LTC4) is a very potent bronchoconstrictor, and is believed to be an important mediator during immediate (IAR) and late asthmatic response (LAR). No direct measurement of LTC4 in lung tissue during IAR and LAR has been reported, however, and its localized site in the lung remains unclear. In an effort to clarify these issues, the content of LTC4 in lung tissue was evaluated at the onset of antigen-induced IAR and LAR, and the distribution of LTC4 was examined by immunohistochemistry. IAR and LAR were induced by inhalation of aerosolized ovalbumin (OA) in conscious guinea pigs. The development of IAR and LAR following inhaled OA exposure was determined in sensitized guinea pigs by measurement of respiratory resistance using the oscillation method. LTC4 in lung tissue was measured by radioimmunoassay at six different stages (S1: non-treated group; S2: group before OA-challenge following sensitization; S3: IAR group; S4: group two hours after IAR; S5: LAR-positive group; S6: LAR-negative group). For immunohistochemistry, non-treated guinea pigs and the sensitized animals at the onset of LAR were used. Lung sections were stained with anti-LTC4 antibody by avidin biotin peroxidase complex method (ABC method). About 70% of the guinea pigs displayed IAR, followed by LAR that peaked at 6-20 hours after OA challenge. The LTC4 content in lung tissue was significantly increased (p less than 0.01) at the onset of IAR, but was significantly decreased (p less than 0.01) after two hours, and significantly increased (p less than 0.01) at the onset of LAR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625401 TI - [Mediastinitis with bilateral empyemas following neck phlegmon]. AB - A 46-year-old male complaining of fever and neck swelling was transferred to our department because of bilateral empyemas in the pleural spaces following neck phlegmon. A culture of the right pleural effusion obtained at his local hospital revealed Gram-positive anaerobic cocci. Chest roentgenogram showed bilateral effusions and widening of the upper mediastinum. Neck roentgenogram confirmed widening of the retropharyngeal space. CT clearly demonstrated a continuous lesion from the neck to the mediastinum and occupying the pleural spaces bilaterally. The patient responded to intravenous antibiotics and tube drainage of the pleural cavities, and was discharged after 10 weeks of hospitalization. Because no mediastinal abscess requiring drainage was recognized on CT, surgical drainage of the mediastinal space was not performed. Sequential CT was used to follow the lesion in the retropharyngeal space, mediastinum and pleural spaces, to check and reposition the tubes for drainage of pleural exudate. PMID- 1625402 TI - [Pulmonary tuberculosis in youth]. AB - The study of the group younger than 29 years of age with pulmonary tuberculosis was carried out. Thirty seven out of 287 tuberculosis patients who were discharged from National Chiba-Higashi Hospital in 1989 were enrolled. Only 5 patients (13.5%) were associated with complication. The smear and culture of sputum for acid-fast bacilli were positive in 30 cases (81.1%) and chest X-ray films revealed cavitary lesion in 31 cases (83.3%). Many of them were moderately advanced cases. Twenty four of them were found symptomatically, 10 by mass survey and 3 under treatment of other diseases. The total delay of symptomatic patients was 8.5 weeks until 80% of them were definitely diagnosed. The days of hospital stay were 122 until half patients were discharged. Five of them (13.5%) were non Japanese and all stayed in Japan illegally. Their condition was rather severe. PMID- 1625403 TI - [Study on familial attacks of pulmonary tuberculosis in Sapporo City]. AB - We studied familial attacks of pulmonary tuberculosis in Sapporo City from 1987 to 1990. There were 146 sources of infection. Two hundred twenty three were infected secondly. Chemotherapy was given to the 75 out of 223 patients. Chemoprophylaxis was given to the total of 148 children. The average ages of the sources, those who were infected secondly and those who had given chemoprophylaxis were 44.8, 32.2 and 7.7 years of age respectively. The ratio of male vs female was 1:0.4 among the sources. The main routes of transmission of this disease were from husbands to wives, from fathers to children, and from grandfathers to grandchildren. The patients who did not have health examination in the preceding one year of their present diagnoses had more severe state of disease as well as higher Gaffky degrees and were treated for more than one year. The infectious patients accounted for more than 50% of the active pulmonary tuberculosis in Sapporo City in 1990. Tuberculin skin test has been performed in almost cases of family examination and the period of chemoprophylaxis has been standardized along the guideline for the chemoprophylaxis by Japan Tuberculosis Association and the Ministry of Health and Welfare. Family and relatives of the patient who expectorates tuberculosis bacilli should take at least one examination annually. Younger people should take it more frequently and chemoprophylaxis should be given to the child whose reaction of Tuberculin skin test is strongly positive. PMID- 1625404 TI - [Detection of mycobacteria by polymerase chain reaction]. AB - The polymerase chain reaction (PCR) was used to detect mycobacterial DNA sequences in the cultured or the clinical specimens. Four oligonucleotide primers derived from the sequence of a gene coding 65-kilodalton antigen of Mycobacterium tuberculosis amplified DNA samples of all the 11 species of mycobacteria tested. Serial dilution of M. bovis BCG showed that DNA extracted from only 12 bacilli was enough for the detection by PCR method. However, mycobacteria in sputum were detected by PCR when more than 10(3) bacilli were present. The PCR method may become a useful tool for the rapid diagnosis of mycobacterial infections. PMID- 1625405 TI - [A radiographic progression during and after initial chemotherapy for pulmonary tuberculosis]. AB - Transient radiographic progressions during or after antituberculous chemotherapy were observed in 60 (4.5%) out of 1,321 cases with active pulmonary tuberculosis who received an initial combination chemotherapy including INH and RFP. The radiographic patterns of these progressions were classified into a singular and a gregarious pattern. A correlation between the two radiographic patterns and a positive or negative culture in sputum at the time of the radiographic progressions was studied, revealing significantly more frequent singular patterns in culture negative cases while more frequent gregarious patterns in culture positive cases. In a majority of the cases, radiographic progressions developed within 3 months after an initiation of chemotherapy. Either of the increased shadows during chemotherapy or after completion of chemotherapy showed an improvement in a moderate degree or over and a good prognosis thereafter by continuous administration of the same drugs or under observation without retreatment respectively. It is concluded that radiographic progressions appeared during an intensive chemotherapy or after its completion do not always require changing the antituberculous drugs or resumption of chemotherapy. PMID- 1625406 TI - [A case of adenosquamous carcinoma with unknown origin and with superior vena cava syndrome as the first symptom]. AB - This report is concerning a case of adenosquamous carcinoma having unknown origin and showing SVC syndrome as the first symptom. A 44 year-old man was admitted to our hospital because of facial edema at the beginning of April 1990. He was diagnosed as having a mediastinal tumor of the SVC syndrome type. Resection of the SVC tumor and part of the pericardium was performed on June 20, 1990. The operation had extraordinary findings. Lymph nodes adhering to tumor invaded the adjacent right side of the trachea and were situated in a rosette-like form. Furthermore, a part of the tumor stemmed into the lumen of the superior vena cava causing complete obstruction. The pathological diagnosis of the SVC tumor was adenosquamous carcinoma, however, no clinical examinations could identify its original matrix. Mediastinal tumors of unknown origin are reported as about 1% of all mediastinal tumors, and are responsible for 0.68% of all carcinomas in the mediastinum. This was one experience of a rare case of mediastinal tumor having unknown origin and showing SVC syndrome as the first symptom. PMID- 1625408 TI - [PTCA and left ventricular systolic function (evaluation by exercise two dimensional echocardiography)]. AB - Successful transluminal coronary angioplasty (PTCA) should improve left ventricular systolic function. To assess the effect of this procedure 25 patients with coronary heart disease were examined before and 3-to 5 days after successful PTCA with electrocardiographic treadmill exercise test, and exercise two dimensional echocardiography (modified Bruce protocol). Echocardiographic examination was obtained prior to and immediately following exercise. Left ventricular ejection fraction and segmental wall motion at the baseline and immediately after exercise were assessed. Electrocardiographic evidence of ischemia was found in 16 of 25 patients prior to PTCA and in 9 patients after PTCA. Following angioplasty, exercise duration was increased and the exercise induced angina rate was significantly decreased. Ejection fraction did not change significantly in patients prior and after PTCA (52 +/- 10% versus 55 +/- 16%, p = NS). Following angioplasty, ejection fraction increased from 55 +/- 10% (rest) to 64 +/- 11% (exercise) (p less than 0.001). New exercise-induced echocardiographic segmental wall motion abnormalities were found in 16 of 25 patients prior to PTCA and in only one patient following PTCA. Significant improvement of ejection fraction and segmental wall motion were also observed in 11 patients with old myocardial infarction subjected to successful angioplasty of infarct-related coronary artery. Opposite to post-exercise results, the resting mean values of these echocardiographic parameters did not differ significantly between pre and post-PTCA examinations. These data demonstrate an improvement in systolic left ventricular function and better exercise tolerance following successful PTCA. This occurs also in patients with old myocardial infarction after angioplasty of infarct-related coronary artery. Two-dimensional exercise echocardiography may be helpful in assessing the early results of successful angioplasty. PMID- 1625407 TI - [Primary arterial hypertension. Treatment with captopril and function of the left heart ventricle, concentration of catecholamine in blood and activity of renin]. AB - We evaluated the effect of captopril treatment on left ventricular mass (LVM) and function in sustained mild-to-moderate primary hypertension. In 16 men aged 34.5 +/- 6.4 yrs. M-mode echo and pulsed wave Doppler recordings were obtained prior to and after 2 months captopril treatment (50-150 mg daily). No significant changes in heart rate, systolic blood pressure, ejection fraction, fractional shortening, cardiac output, LVM and Doppler-derived indices of mitral inflow were observed. Diastolic blood pressure measured during examination fell from 102.2 +/ 13.3 to 90.3 +/- 9 mmHg (p less than 0.026). No consistent correlations between catecholamines and indexes of left ventricular function were found. Two-month captopril therapy in mild-to-moderate hypertension results in diastolic blood pressure lowering with no effect on LVM or left ventricular function. PMID- 1625409 TI - [Does the appearance of pro-arrhythmic response to anti-arrhythmic drugs have prognostic significance?]. AB - Study was undertaken to assess whether proarrhythmic response to antiarrhythmic drug is a risk factor for cardiac death in patients (pts) with ischaemic heart disease (IHD). In 782 pts with IHD and frequent and/or complex ventricular ectopic beats (VEB) 1041 drug tests guided by 24 hour Holter monitoring were conducted. The following drugs were assessed: propranolol, disopyramide, mexiletine, amiodarone. Pro-arrhythmia was defined according to Velebit: 1/greater than or equal to 4-fold increase in VEBs, 2/greater than or equal to 10 fold increase in repetitive forms of 3/new occurrence of ventricular tachycardia or ventricular fibrillation (VT/VF). Proarrhythmic effect was observed in 8.4% of pts and in 7.9% of drug tests. The frequency with individual drugs ranged from 5.7% to 9%. No drug was completely free of this type of reaction. Antiarrhythmic drugs inducing arrhythmogenic response were eliminated. Pts were followed-up for a mean of 22 months (range 1-49). Chronic antiarrhythmic treatment was conducted. Pts were discharged taking the agent deemed most effective for suppression of arrhythmia. Follow-up visits were made every 6-12 months. All cases of death were verified. In long-term observation cardiac death and sudden death occurred in 53 and 32 pts. With actuarial analysis (Kaplan-Meler method, log rank test) there was significant difference in cardiac death (p less than 0.05) of pro-arrhythmia (+) compared with ++pro-arrhythmia (-) pts at yr (11% v 4%, 7% v 3%) and 3 yr (24% x 11%, 16% v 7%). The relative importance of baseline clinical variables in predicting survival was assessed with a stepwise Cox regression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625410 TI - [Role of collagen in myocardium]. PMID- 1625411 TI - [Renin-angiotensin systems--pathophysiologic, diagnostic and therapeutic aspects]. PMID- 1625412 TI - [Circulatory insufficiency, ischemic disease, arrhythmia and the renin angiotensin-aldosterone system and angiotensin converting enzyme inhibitors]. PMID- 1625413 TI - [Healing with heart]. PMID- 1625414 TI - [Stress and heart disease; it's source and possible defeat]. PMID- 1625415 TI - [Type A behavior and ischemic heart disease]. PMID- 1625416 TI - [How to treat ventricular arrhythmia (comparison of Polish and international inquiry with commentary)]. PMID- 1625417 TI - [In what diseases do the patients have to be provided with a stoma by operative medicine?]. PMID- 1625418 TI - [Children as stoma patients]. PMID- 1625419 TI - [The preoperative tasks of the stoma therapist]. PMID- 1625421 TI - [What are the patient's requirements from modern stoma care materials]. PMID- 1625422 TI - [On the track of the enigma of aging. The personal "un-folding"]. PMID- 1625420 TI - [Innovations for a better quality of life]. PMID- 1625423 TI - [The stoma patient's skin--skin protective materials in conflict with the stoma patient's skin]. PMID- 1625424 TI - [Treatment of skin irritations in stoma patients from a nursing viewpoint]. PMID- 1625425 TI - [Complications and therapy in colostomies and ileostomies]. PMID- 1625426 TI - [Coloplast assura]. PMID- 1625427 TI - [Problems in the selection of stoma care products in fixed payment groups]. PMID- 1625428 TI - [Modern ambulatory care of stoma patients]. PMID- 1625429 TI - [Infections in the area of the stoma and their treatment]. PMID- 1625430 TI - [Information and counseling for stoma patients by the health products industry]. PMID- 1625431 TI - [Care for stoma patients in the new Federal Territories yesterday and today--new concepts in patient care]. PMID- 1625432 TI - [Nutrition for stoma patients]. PMID- 1625433 TI - [Cost containment?]. PMID- 1625434 TI - [Psychological factors in the acceptance of disease in patients with stomas]. PMID- 1625435 TI - [Disclosure by the physician about mortal illness]. PMID- 1625436 TI - [Professional situation and professional perspectives for stoma therapists]. PMID- 1625437 TI - [Experiences with the use of Coloplast Assura]. PMID- 1625439 TI - [Am I what I create out of myself?]. PMID- 1625438 TI - [Brain surgery using endoscopy. Thin and flexible instruments, many functions, fewer tissue injuries]. PMID- 1625440 TI - Intracellular signal transduction and the control of endothelial permeability. PMID- 1625441 TI - Spinal cord microglia in experimental allergic neuritis. Evidence for fast and remote activation. AB - We have studied the response and the spatial distribution pattern of microglial cells during experimental allergic neuritis induced in the Lewis rat by the transfer of varying doses of activated T cells specific either for the P2 or P0 protein. The microglial reaction was studied immunocytochemically at the light and electron microscopic level using a panel of monoclonal antibodies which included two recently produced antibodies against rat microglial cells, Murine Clone 101 and 102. Activation of microglial cells became apparent through changes in their immunophenotype and morphology within 48 hours of T cell transfer and therefore preceded the onset of clinical disease. Activated microglial cells showed an increased expression of the complement type three receptor, the murine clone 101 and 102 determinants and major histocompatibility complex antigens. The microglial reaction in experimental allergic neuritis occurs at a site remote from the inflammatory changes in the peripheral nerve, the microglial reaction being most prominent in the dorsal and ventral grey matter of the lumbar and the thoracic spinal cord. Similar changes were also observed at this time in the terminal projection fields of the primary, afferent, sensory fibers, such as the nucleus gracilis. Subsequently, after 7 days, motoneurons, particularly in the ventral grey matter of the lumbar spinal cord, were ensheathed by perineuronal microglial cells. These perineuronal microglial cells were in close contact with the neuronal plasma membrane and occasionally appeared to detach afferent synaptic terminals from the surface. Microglial responses were not detected in animals injected with nonpathogenic T cells specific either for the purified protein derivative or ovalbumin. This early activation of microglial cells observed in experimental allergic neuritis suggests that a rapid and remote signaling might be operating in the microglial responses during T cell-mediated autoimmune diseases. PMID- 1625442 TI - Mercuric chloride-treated brown Norway rats develop widespread tissue injury including necrotizing vasculitis. AB - BACKGROUND: Mercuric chloride (HgCl2) induces a T cell-dependent autoimmune syndrome in Brown Norway (BN) rats, characterized by polyclonal B cell activation and circulating autoreactive T cells. A number of autoantibodies are produced, including antibodies to glomerular basement membrane, and there are circulating immune complexes. However, histologic evidence of tissue injury in this model has previously been reported to be rare. EXPERIMENTAL DESIGN: Six BN rats were given five injections of HgCl2, each of 1 mg/kg, over 10 days. Controls were four BN rats given equal volumes of saline and 10 Lewis rats given the same amount of HgCl2. Blood samples were taken thrice weekly. Animals were killed at various stages, necropsies performed, and organs histologically examined. The effect of pretreatment with broad spectrum antimicrobial drugs was examined by comparing two further groups of six BN rats: one group was pretreated with tylosin, ivermectin, and metronidazole before HgCl2 was given, and the other group received no pre-treatment. RESULTS: HgCl2-treated BN rats developed inflammation and ulceration of the skin which was most marked at mucocutaneous junctions. Macroscopic examination of internal organs showed hepatomegaly and gross haemorrhagic lesions in the wall of the gut, most marked in the duodenum and caecum. Microscopically, the skin lesions were characterized by a subepidermal mononuclear cell infiltrate with occasional hair shaft necrosis. In the liver there was a periportal mononuclear cell infiltrate, and in the gut there was intense submucosal inflammation and a leucocytoclastic vasculitis accompanied in places by mucosal ulceration. Lewis rats (which are not prone to mercury-induced autoimmunity) showed no such changes after receiving HgCl2, nor did control BN rats given saline. BN rats pretreated with broad spectrum antimicrobial agents and then given HgCl2 showed milder histologic abnormalities, although antimicrobial treatment did not affect the antiglomerular basement membrane autoantibody response. CONCLUSIONS: We have identified a syndrome induced by mercuric chloride in BN rats in which there is evidence of tissue injury in many organs, with some features in common with graft-versus-host disease. There is also necrotizing leucocytoclastic vasculitis affecting the gut, and the importance of this is enhanced by the description in the accompanying paper of autoantibodies similar to those found in human systemic vasculitis. Our observations strengthen the analogies between this model and human autoimmune disease. PMID- 1625443 TI - Growth and dissemination of human malignant melanoma cells in mice with severe combined immune deficiency. AB - BACKGROUND: The severe combined immune deficiency (SCID) mouse is lacking mature B and T lymphocytes and may be permissive for human tumor growth and metastasis. EXPERIMENTAL DESIGN: SCID mice received human melanoma cells of diverse origins including: 2 established cell lines, 4 early passage cell lines, and fresh or cryopreserved cells obtained directly from 9 patient biopsies. They were introduced into SCID mice via intraperitoneal, subcutaneous and intravenous injections. RESULTS: Tumor growth occurred with each of the 15 melanoma specimens for a take rate of 100% considering cell source. In addition, 60% of the 102 total mice injected displayed tumor growth in at least one site. The most consistent tumor growth (77%) occurred after intraperitoneal injection. Tumors developed in 41 and 48% of mice injected subcutaneously and intravenously, respectively. The mice developed both local tumor growth with palpable tumor nodules at injection sites and hematogenous and/or lymphatic dissemination to multiple sites in the abdominal and thoracic cavities. The number of metastases per animal averaged 16.3 and the number per organ ranged from 1 to 38. Melanotic and amelanotic tumor nodules obtained from a single patient retained their original characteristics with regard to melanin production after passage in the SCID mouse. The appearance of the human melanoma cells in SCID mouse tissues ranged from implants on the organ capsule to frank parenchymal organ involvement and vascular invasion. Some small foci of tumor were only detected using immunohistochemistry with monoclonal antibodies against the S-100 and HMB-45 to melanoma-related antigens. CONCLUSIONS: We conclude that the SCID mouse consistently supports growth, invasion, and metastatic spread of human melanoma cells, including specimens obtained from fresh patient biopsies. The SCID mouse will serve as a relevant in vivo model for studying the biology of human malignant melanoma and screening new therapeutic agents. PMID- 1625444 TI - An immune model of beryllium-induced pulmonary granulomata in mice. Histopathology, immune reactivity, and flow-cytometric analysis of bronchoalveolar lavage-derived cells. AB - BACKGROUND: Beryllium compounds can cause acute and chronic lung injury in humans. Although models of chronic granulomatous lung disease have been established in various animal species, a murine model of beryllium-induced chronic lung disease has not been established. EXPERIMENTAL DESIGN: Beryllium was introduced intratracheally either as a soluble salt (BeSO4) or in particulate form (BeO). Various preimmunization protocols were used to enhance immune mediated pulmonary changes. Cells obtained by bronchoalveolar lavage (BAL) were analyzed using flow cytometry, and the observations correlated with in vitro immune responses and with lung histopathology. RESULTS: Histologic changes were consistently found in mice preimmunized with BeSO4.4H2O plus syngeneic serum. Addition of complete or incomplete Freund's adjuvant to the preimmunization protocol was not necessary to induce granulomatous changes. BAL showed a significant increase in lymphocytes at 2, 4, and 8 weeks after intratracheal BeSO4. Approximately one-third of BAL lymphocytes expressed the gamma/delta T lymphocyte receptor at 2 weeks; at 4 weeks the lymphocytes were predominantly Thy1+, L3T4+ (CD4+) and expressed only the alpha/beta T lymphocyte receptor. Only BAL lymphocytes from mice preimmunized with BeSO4/serum and challenged with BeSO4/serum showed significant in vitro proliferation in response to BeSO4. Macrophage activation antigens (Mac-2, Mac-3) were expressed only during the acute inflammatory phase (2 weeks) whereas increased expression of a monocyte/macrophage antigen (Mac-1) remained elevated beyond the inflammatory period in some instances. Attempts to induce similar lesions in BALB/c and C57BL6/J mice were unsuccessful. Genetic differences at the H-2 major histocompatibility complex gene complex may account for the differential responses to BeSO4 among various mouse strains. A single exposure to BeO also induced histopathologic changes in the lung which correlated with BAL cellularity, but these changes were only observed 8 months after exposure and did not proceed to frank granulomas. CONCLUSIONS: A murine model of granulomatous lung disease may prove useful in understanding the genetic and immunologic factors that determine the response to beryllium. The animal model may also have implications for pulmonary sarcoidosis, a disease of unknown cause(s), whose disease manifestations and BAL profiles are difficult to distinguish clinically and pathologically from chronic beryllium disease. PMID- 1625445 TI - Sequential assay of human milk immunoglobulins shows a predominance of lambda chains. AB - BACKGROUND: Little is known of the light chains associated to heavy chains in secretions immunoglobulins. We investigated the partition of light chains in a mucosal fluid of easy access and major physiologic importance: human milk. EXPERIMENTAL DESIGN: This study provides a sequential analysis of IgA, lambda and kappa chains levels in human milk during the first days of lactation. The levels of IgA alpha-chain and of lambda and kappa light chains of immunoglobulins were assayed in 162 samples of normal human milk collected during the first night of lactation, using a classical immunonephelometric assay. A specific enzyme-linked immunosorbent assay was developed to specifically measure the levels of IgA linked light chains, yielding similar values. Ten samples of normal human serum obtained from healthy adults were tested in parallel. RESULTS: The highest levels were observed during the first 3 days of lactation, and a plateau appeared for the three proteins after day 4. Mean lambda chains levels were consistently higher than these of kappa chains, resulting in a reversed kappa/lambda ratio, significantly different from the classical 2:1 serum ratio confirmed with this method on control samples. CONCLUSIONS: This study indicates that milk immunoglobulins use an unusual partition of light chains, especially in IgA. PMID- 1625446 TI - Embryology and morphology of microphthalmia in transgenic mice expressing a gamma F-crystallin/diphtheria toxin A hybrid gene. AB - BACKGROUND: Transgenic mice in which elongating lens fiber cells were ablated resulting in microphthalmia have been reported, however, their embryology and detailed morphology have not. EXPERIMENTAL DESIGN: The morphology of homozygous and hemizygous CDI, transgenic mice carrying the gamma FDT-A gene was studied by light microscopy on different days of gestation as well as postpartum. The findings were compared with normal CD-1 wild type controls. RESULTS: The earliest changes in mouse embryos transgenic for the gamma F-crystallin/diphtheria toxin A transgene are seen on day 12, when apoptotic cells appear in the area of elongation. In hemizygous embryos, ocular development is relatively normal until day 17 when the lens and eye are slightly smaller than normal and the lens vesicle is filled with abnormal lens material. At this time, the posterior capsule of the lens may rupture, releasing abnormal lens material which disperses throughout the eye, perturbing growth and other ocular structures. Additional breaks may subsequently occur and the ultimate morphology of the hemizygotes correlates with when the posterior capsule ruptures, how much lens material is released, and where it disperses. In homozygous embryos, due to extensive ablation of lens fiber cells, the "lens" becomes a diminutive mass of abnormal lens material, posteriorly located within the eye, and otherwise unable to fulfill its mechanical or inductive role in the development of the cornea, anterior chamber, iris, ciliary epithelium, and zonules with the result that all of these structures are markedly abnormal or absent. In addition, the lens is necessary for the accumulation of vitreous which in turn is required for the growth of the eye as a whole. In homozygous animals, vitreous does not accumulate and severe microphthalmia results. CONCLUSIONS: This study confirms and extends previous observations and conclusions on the central, orchestrating role of the lens in the development of the eye and illustrates the power of transgenic technology to elucidate the finer points of mammalian ocular development. PMID- 1625447 TI - Ultrastructural pathology of experimental autoimmune uveitis. Quantitative evidence of activation and possible high endothelial venule-like changes in retinal vascular endothelium. AB - BACKGROUND: Experimental autoimmune uveitis (EAU) is a highly organ-specific autoimmune disease in which the target is the retinal photoreceptors. It is well recognized as a model of uveoretinitis in humans. The mechanisms that control the homing of sensitized lymphocytes and other leukocytes to the retina is unknown. The aim of this study was to investigate changes in the retinal vasculature that may be involved with aiding leukocyte-endothelial cell interactions and subsequent extravasation of leukocytes into the retina. EXPERIMENTAL DESIGN: Lewis rats immunized with S-antigen were used to produce EAU. The retinal vasculature was assessed by morphologic (light and electron microscopy) and morphometric techniques at various stages in the generation and course of the disease (days 3, 7, 11, 14, 21, 28 and 49 postimmunization) for evidence of endothelial cell (EC) activation and leukocyte-EC interaction. Image analysis of the retinal vessels at the electron microscopic level was performed to detect alterations in the thickness and irregularity of the EC surface, both considered to be important in lymphocyte homing in the high endothelial venules (HEVs) of lymphoid tissues. Control values were obtained from normal eyes, pertussis-only treated animals, and normal lymph node HEVs. RESULTS: The clinical and histopathologic changes in the eyes were consistent with previous descriptions of EAU and included perivasculitis, focal mononuclear infiltrate in the outer retina, and choroid with destruction of the photoreceptor outer segments and eventually loss of large portions of the outer retina. During the course of EAU, a significant proportion of retinal venules underwent both qualitative and quantitative morphologic changes including EC activation evident as increased cytoplasmic organelles, a 230% average increase in mean EC thickness, and a concomitant 4-fold increase in irregularity of the EC, that produced plump irregular EC with deep intercellular clefts. These alterations were maximal at day 21, however from day 11 onward, large numbers of lymphocytes and monocytes were observed adhering to or lodged in the clefts of plump EC, migrating through the EC cytoplasm, or lying beneath the EC. CONCLUSIONS: The characteristics acquired by the retinal venules during EAU are reminiscent of HEVs. This study suggests that tissue-specific changes in the endothelial cells of retinal venules may be responsible for the homing of S-antigen specific autoreactive lymphocytes to the target organ in this model of retinal autoimmunity. PMID- 1625449 TI - Expression of type I and III collagens and fibronectin after transection of rat sciatic nerve. Reinnervation compared with denervation. AB - BACKGROUND: The regeneration of transected peripheral nerve is thought to happen with the help of cell-cell and cell-extracellular matrix interactions. We studied the role of axon in controlling the expression of extracellular matrix genes in transected peripheral nerve. EXPERIMENTAL DESIGN: Left sciatic nerves were transected in a total of 132 rats. In half of the animals, regeneration was allowed to occur, while in the other half regeneration was prevented. The expression of type I and III collagen and fibronectin genes was studied proximally and distally to the site of transection up to 8 weeks after the injury both with and without axonal reinnervation. For Northern blotting, the endoneuriums of 10 animals from both groups were used at each time point. For in situ hybridization, transverse sections of the nerves were used to observe cellular source of the mRNA. In addition, immunohistochemistry was performed in sequential sections in order to identify the cells expressing the studied extracellular matrix genes. RESULTS: Northern hybridization showed the highest expression of type I and III collagens in the distal stumps of transected nerves 7 to 14 days after nerve transection both with and without axonal reinnervation. The proximal site of the injury showed strong expression of the extracellular matrix genes which lasted markedly longer than in the distal site. In situ hybridizations showed that epi-, peri-, and endoneurium are active for producing type I collagen. S-100 immunohistochemistry suggested that the cell type responsible for the production of type I collagen in the endoneurium during the peripheral nerve regeneration is endoneurial fibroblast. CONCLUSIONS: During peripheral nerve regeneration the expression of the extracellular matrix genes does not seem to be simply related to the presence of axons. Endoneurial fibroblasts contribute to the production of collagen type I and apparently to that of fibronectin, which thus is not totally derived from plasma. PMID- 1625448 TI - Nasopharyngeal carcinoma and retinoblastoma gene expression. AB - BACKGROUND: The pathogenesis of nasopharyngeal carcinoma (NPC) is not well defined yet. To evaluate oncosuppressor genes in NPC, two NPC cell lines were investigated for expression of the retinoblastoma (RB) gene. EXPERIMENTAL DESIGN: We used Western blotting to identify RB protein species, and checked the RB gene conformation by Southern blotting. We also used immunohistochemistry, in situ nucleic acid hybridization, and in situ extraction of RB protein to observe RB protein in NPC culture cells. RESULTS: Both cell lines as well as sublines could synthesize normal RB proteins of 110, 113 and 114 kilodaltons. These cells showed no RB DNA rearrangement. Most interphase cells showed variable amounts of anti-RB reaction product in their nuclei when immunostained by 13 monoclonal antibodies. However, all mitotic cells contained RB protein either in the cytosol or the chromosomes, depending upon the mitotic phase. The level of RB mRNA increased slightly in mitotic cells as compared with interphase cells. Double localization of bromodeoxyuridine and RB protein in NPC cells and localization of RB protein in synchronized NPC cells in different phases of the cell cycle revealed random RB protein expression in each individual tumor cell. Co-localization of RB mRNA and RB protein in interphase cells showed a different degree of RB message expression in each cell. Low-salt hypotonic buffer could remove a fraction of RB protein from stained interphase nuclei. A similar finding with slight variations was observed in 16 other cancer cell lines. CONCLUSIONS: These data indicate that our NPC cell lines contain no obvious RB gene rearrangement, but each cancer cell may have an abnormal expression of RB mRNA and protein. This phenomenon may also be true in other cancer cell lines with a normal RB gene. PMID- 1625450 TI - Multiple sclerosis. Interactions between oligodendrocytes and hypertrophic astrocytes and their occurrence in other, nondemyelinating conditions. AB - BACKGROUND: The proliferation of oligodendrocytes and their association with hypertrophic astrocytes has been previously described in resolving multiple sclerosis (MS) lesions. EXPERIMENTAL DESIGN: Central nervous system lesions of different ages were examined from 9 cases of MS with clinical histories ranging from 8 weeks to 13 years and in a variety of non-MS conditions. RESULTS: In MS, these associations were found to occur most frequently in acute, actively demyelinating (as opposed to resolving) lesions. They also occurred, albeit rarely, in chronic active and chronic silent MS plaques and in areas showing remyelination or normal myelination adjacent to lesions. Immunocytochemistry revealed that the oligodendrocytes occurred in increased numbers and displayed enhanced reactivity for HNK-1, similar to previous studies that claimed such cells to be of recent origin. Ultrastructurally, hypertrophic astrocytes in the lesion center usually possessed no formed bundles of intermediate filaments, but rather displayed a finely granular cytoplasm. Towards the perimeter, they contained bundles of filaments and showed increased staining with anti-glial fibrillary acidic protein antibody. The interactions involved the close apposition to, and internalization of oligodendrocytes by astrocytes, between which membrane specializations occurred, suggestive of an adhesion event. Identical glial associations were also seen in various non-MS conditions. In most of the latter cases, there was evidence of central nervous system inflammation and/or destruction. CONCLUSIONS: These observations underscore the increased frequency of the glial cell phenomenon in active MS lesions, its ubiquity in diseases of different etiologies and the need for careful scrutiny of control central nervous system tissue in assessing the specificity of phenomena attributed to MS. It is suggested that these glial associations may represent a transient protective mechanism and may be related to local cytokine production. PMID- 1625451 TI - Hyponatremia: manifestations and treatment. AB - All hyponatremic states have in common elevation of vasopressin. Without this the loss of salt would be followed by appropriate diuresis and normonatremia. If hyponatremia is triggered by a volume change as in heart failure or portal cirrhosis not only is ADH released but the mechanisms that control salt retention create an essentially sodium free urine, always less than 20 mEq/L. If the initial event is inappropriate ADH secretion whether it be cerebral disease, neoplasm, a pulmonary lesion or a growing list of drugs; there is no related signal for salt retention and urine sodium and tonicity are high, the latter usually higher than that of plasma. If salt loss is due to intrinsic renal disease, diuretics, osmotic or otherwise, or adrenal failure urinary sodium is variable depending upon the magnitude of the response to volume of salt retaining factors. Because hyponatremia is often present with major illness and because more than one factor may be involved in its genesis, the establishment of its origin and appropriate treatment remain a diagnostic and therapeutic challenge. PMID- 1625452 TI - Medicine, illness, and creativity. PMID- 1625453 TI - Medical burnout. PMID- 1625454 TI - E-Speed dental film, time to take a new look? AB - Although various studies have indicated that there is no statistical difference in the diagnostic value between D- and E-speed films, and resolution and contrast were reported as being identical, the general acceptance of E-speed film has been slow. The dental profession is faced with a decision: Do we use the slower D speed film that might be more "cosmetic" in appearance or use E-speed that can reduce radiation by as much as 50 percent? Recent research has indicated that 85 percent of parotid gland exposure is the result of dental radiography and carries an increased risk for meningiomas and tumors. It is the opinion of some that risk factors now dictate that only the fastest speed (E-speed) film should be used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625455 TI - Nifedipine-induced gingival hyperplasia. AB - Gingial hyperplasia is a complication which may be seen in a significant number of patients taking nifedipine (Procardia, Pfizer) a commonly used medication for cardiac vessel dilitation. This is a report of gingival changes in a 43-year-old hypertensive male who began using the calcium channel blocking agent during his active dental treatment. Gingival hyperplasia developed which was severe enough to alter the course of his dental treatment and prompt his changing to other medications to control his blood pressure. The recognition that the drug was responsible for the hyperplasia led to prompt and effective methods to resolve this problem. PMID- 1625456 TI - Management of penetrating injuries to the carotid artery. PMID- 1625457 TI - A woman with superior vena cava syndrome. PMID- 1625458 TI - The sympathy factor. PMID- 1625459 TI - Norplant. PMID- 1625460 TI - Patients/physicians disagree on definition of quality. TMA Communications and Public Service Committee. PMID- 1625461 TI - Hippocrates lives! PMID- 1625462 TI - Too grievous to bear. PMID- 1625463 TI - Ethics Committee shares ANA's statement on ethics and human rights. PMID- 1625464 TI - Hospice nursing care--comfort--sharing. PMID- 1625465 TI - Kentucky nurse testifies in Washington, D.C. Testimony on nursing education and research funding before the Labor, Health and Human Services, Education and Related Agencies Subcommittee of the House Appropriations Committee, April 28, 1992. PMID- 1625466 TI - Chemical dependency: in the curriculum. PMID- 1625467 TI - In vitro culture of hematopoietic progenitors in the diagnosis of blood disorders. PMID- 1625468 TI - Phenotypic diversity and prognosis of adult T-cell leukemia. AB - We examined phenotypically 107 patients with adult T-cell leukemia (ATL), using a panel of monoclonal antibodies, in order to clarify the occurrence of aberrant phenotypes, and to determine the correlation between phenotypic diversity and prognosis. The incidence of the typical (CD4+.CD8-) phenotype, the double negative (CD4-.CD8-), the double-positive (CD4+.CD8+), and the CD8-positive (CD4 .CD8+) phenotypes was 81%, 7%, 7%, and 4%, respectively. The median survival time (MST) for all patients was 10.0 months with 17% survival at 2 years. The patients with typical phenotypes had a 10.2 month MST with 20% survival at 2 years, significantly better than the patients with the unusual phenotypes whose MST were 4.9, 7.8, and 2.6 months, respectively, for the double-negative, double-positive, and CD8-positive phenotypes. Lack of antigens reactive with CD2, CD3, CD5, and WT31 monoclonal antibody panels was one factor in bad prognosis, but the presence of CD4 and CD8 antigen abnormalities was much more significant. PMID- 1625469 TI - Monocytic differentiation induction of HL-60 cells by MC 903, a novel vitamin D analogue. AB - 1.25 (OH)2D3 is a potent inducer of differentiation of leukaemic cells into a monocytic direction. However, therapeutic application is difficult because of the development of hypercalcaemia. We examined a novel vitamin D analogue, MC 903, which is at least 100 times less effective on calcium metabolism in rats than 1.25 (OH)2D3. Using the HL-60 cell line, differentiation was measured with a comprehensive panel of qualitative and quantitative parameters. Development of monocytic cells was shown morphologically, immunophenotypically and functionally by increased capability of reducing NBT (vs cultures without MC 903, p less than 0.0001) and by qualitatively and quantitatively increased non-specific esterase activity. Furthermore, a concomitant decreased activity of myeloperoxidase and lactate dehydrogenase was noticed. In conclusion, MC 903 is a potent inducer of monocytic differentiation, comparable with 1.25 (OH)2D3 and will therefore be an interesting and potential therapeutic agent for studies in human acute leukaemia. PMID- 1625470 TI - Pyrene butanol--an efficient, selective and non-metabolized photosensitizing agent for human myeloid leukemia cells. AB - Methods for ex vivo purging of neoplastic cells from harvested marrow are being developed to increase the efficacy of autologous transplantation. One approach is selective photosensitization, using sensitizing compounds and light radiation. Pyrene-containing fatty acids and lipids are potent photosensitizers, e.g. 12-(1 pyrene)dodecanoic acid (P12), is taken up preferentially by leukemic cells and undergo photoexcitation when exposed to long wave ultra-violet light, resulting in selective killing of leukemic cells. These compounds are incorporated into the neutral- and phospho-lipids of the cells. The presence of intracellular pyrene linked lipids might present a potential hazard in applying these agents for clinical use. We have, therefore, studied a series of other pyrene-linked compounds with the objective of finding a non-metabolizable photosensitizing agent that can be easily removed from the cells. In the present paper we report the results with pyrene butanol (P4-OH), a pyrene linked short-chain alcohol. When compared to P12, P4-OH was found to be taken up by cells most rapidly and reached saturation within minutes. It did not undergo any metabolism and washing the cells with serum-containing salt solutions removed practically all the P4-OH. This compound was found to be an efficient photosensitizer (in terms of concentrations and time of incubation with the cells) and selective to leukemic cells--it caused a 99% reduction in leukemic clonogenic cells under conditions that normal hemopoietic progenitors remained almost intact. These properties make P4-OH a potential photosensitizer for clinical application. PMID- 1625471 TI - Heterogeneity of acquired idiopathic sideroblastic anaemia (AISA). AB - Clinical, haematological and outcome data were studied in 84 patients with acquired idiopathic sideroblastic anaemia (AISA) from a registry of 613 consecutive myelodysplastic syndromes (MDS) recorded by five institutions in western France. Two groups could be identified and compared: 'pure' erythroblastic AISA (AISA-E: 59 pts), and AISA with myelodysplastic features, i.e. dysgranulo and/or dysmegakaryopoiesis (AISA-M: 25 pts). Results were also compared to those of a series of 71 cases of refractory anaemia without sideroblastosis (RA) carried out from the same registry. Dyserythropoiesis was present in 90% of all AISA subtypes, dysgranulopoiesis in 88% of the AISA-M cases; dysmegakaryopoiesis was observed in 44% of AISA-M. Ten patients with both forms of AISA showed high platelet counts. These cases appeared particular in that four of them were associated with a splenomegaly and/or a hyperleucocytosis. They had to be distinguished from myeloproliferative syndromes. Outcome comparison of AISA-E with AISA-M showed a significant discrepancy of survival duration (60 vs 38 months respectively). Progression towards refractory anaemia with excess of blasts or acute leukaemia, was significantly higher for AISA-M than for AISA-E. The risk of transformation increased to 24% for the AISA-M group similarly to those of RA patients (17%). We conclude that AISA must be divided into two categories, 'pure' AISA and AISA-M, because survival duration and risk of transformation are different. PMID- 1625472 TI - VLA molecule expression may be involved in the release of acute myeloid leukaemic cells from the bone marrow. AB - Acute myeloid leukaemia (AML) cells have a variable capacity to egress from bone marrow into peripheral blood. This may be due to a variable lack of adhesion molecules on leukaemic cells. The expression of VLA1, 3, 4, 5, 6, beta 1-chain, LFA1, beta 2-chain, ICAM1 and NCAM appeared to be higher in bone marrow as compared to peripheral blood leukaemic cells, although this only reached significance for beta 1-chain (p less than 0.01). The number of cases with more than 20% positive cells in bone marrow leukaemic cells was lower in immature FAB subtypes (M1, M5a) as opposed to more mature subtypes (M2, M3, M4, M5b) for the adhesion molecules tested. This reached significance for VLA5 (p less than 0.05) and beta 1-chain (p less than 0.007), while there was trend for VLA4. It is discussed that VLA4 and 5 may play a role in the release of leukaemic cells from the bone marrow. PMID- 1625473 TI - Argininosuccinate synthetase gene expression in leukemias: potential diagnostic marker for blastic crisis of chronic myelocytic leukemia. AB - Argininosuccinate synthetase (ASS) activity is hardly detected in human lymphocytes. In this study, we examined the ASS gene expression of various leukemia cells by a polymerase-chain-reaction method. We demonstrate here that (a) acute lymphocytic and acute myelocytic leukemia cells exhibit the highly elevated expression of the ASS gene and (b) chronic myelocytic leukemia (CML) in blastic crisis also exhibits the increase of ASS gene expression while CML in chronic phase, chronic lymphocytic leukemia and adult T leukemia cells show the similar level to that of normal lymphocytes. These results suggest that the ASS gene expression is of value as a diagnostic marker of acute type leukemia, particularly for blastic crisis of CML. PMID- 1625474 TI - Analysis of mutations in the Gs protein alpha subunit gene in human leukaemia. AB - Mutations at codons 201 and 227 that cause oncogenic activation of the gene encoding the Gs alpha subunit protein occur in a subset of human solid tumours. To determine whether such oncogenic mutations occur in leukaemia we have analysed DNA from leukaemic cells from 59 patients representing a spectrum of acute and chronic leukaemia types by direct nucleotide sequence analysis of polymerase chain reaction (PCR) amplified DNA. No mutations were detected at oncogenic hot spots represented by codons 201 or 227, nor in any other codons extending from nucleotide position 196-230 in the Gs alpha subunit gene. This strongly suggests that this region of the Gs alpha gene is highly nonpolymorphic and that oncogenic mutations in this gene are unlikely to play a significant role in the pathogenesis of leukaemia. PMID- 1625475 TI - The linking of anticancer drugs, cell cycle blocks, and differentiation: implications in the search for antineoplastic drugs. AB - The quest for anticancer drugs has been primarily directed at agents that interfere with cell replication, yet the basis for drug-induced cytotoxicity remains unsolved. In our previous studies we noted a relationship between a mitotic block and commitment to terminal differentiation in the murine (Friend) erythroleukemia (FEL) cell. Since anticancer drugs are known to often block cell cycle transit typically in G2/mitosis, we tested a number of anticancer drugs with various modes of action and found that they all committed FEL cells to differentiate. Furthermore, other G2/mitosis-blocking drugs were also effective in inducing commitment. These results suggest (1) a causal relationship involving anticancer drugs, cell cycle block and differentiation, (2) that the search for new anticancer drugs utilize a differentiation assay and include G2/mitosis blocking agents. PMID- 1625476 TI - The combination of quercetin and cytosine arabinoside synergistically inhibits leukemic cell growth. AB - It has been demonstrated that quercetin (3,3',4',5,7-pentahydroxyflavone) inhibits the growth of several cancer cell lines and that the antiproliferative activity of this substance is probably mediated through a binding interaction with type II estrogen binding sites (type II EBS). The effect of quercetin and cytosine arabinoside (Ara-C) alone or in combination, was tested on HL-60 cell growth. Quercetin significantly synergized the inhibitory activity of Ara-C on HL 60 cell growth while rutin, the 3-rhamnosylglucoside of quercetin, neither competed with [3H]estradiol for type II EBS nor was effective alone or in combination with Ara-C. Based on these results, we studied by a clonogenic assay the effect of quercetin and Ara-C alone and in combination on colony formation by human leukemic cells (CFU-L). In all cases both drugs exhibited a dose-related inhibition of CFU-L in a range of concentrations between 10 nM and 10 microM and 0.01 nM and 10 microM for quercetin and Ara-C, respectively. The combination of the two drugs resulted in a synergistic inhibitory activity on CFU-L. Considering that plasma concentrations of quercetin effective in vitro were obtained in vivo without any apparent side effects, we conclude that this report represents further experimental evidence that quercetin could be used in the treatment of acute leukemias. PMID- 1625477 TI - Predicting remission outcome in acute non-lymphocytic leukemia: general principles and their application to residual marrow leukemia. AB - The objective of this paper is to demonstrate the importance of a rigorous and comprehensive evaluation of predictive tests in acute leukemia, especially when these may influence therapeutic decisions. To illustrate these issues, we have chosen an emerging test, early residual bone marrow leukemia, as the example and we have presented actual data from Leukemia Intergroup Studies of adults with first relapse acute non-lymphocytic leukemia induced with high-dose cytosine arabinoside. We show how the choice of a suitable cut-off value to discriminate between patients predicted to have different remission rates is influenced by several variables including the reasons for remission failure, the estimated efficacy and toxicity of the intervention to be employed, and considerations of resource utilization. We suggest that before applying a new predictive test in practice, clinicians should carefully evaluate its performance, and the consequences of its use in their own clinical settings. PMID- 1625478 TI - Emergence of myeloid stem cell line from T-lymphoid blastic phase of chronic myeloid leukemia in culture. AB - A new cell line designated JA-CML was derived from the peripheral blood of a patient with blastic phase CML. Sequential evolution of phenotypic and genetic markers was demonstrated during adaptation from primary to continuous culture in vitro. In the primary sample the majority of blast cells displayed the early T cell markers, CD7, HLA-DR, and TdT, but were negative for the common ALL antigen (CALLA), CD4 and CD8. Simultaneously, unstimulated metaphase cells showed great karyotypic variation with a range of 43-46 chromosomes per cell. Clonal changes included the Ph chromosome t(9;22), loss of the Y and gain of several altered chromosomes. The cells grew slowly in suspension during the first 10 weeks of culture. During that time, cells still expressed the CD7 and HLA-DR antigens. Karyotypic analysis at ten weeks showed a pattern of 46,X,-Y,t(9;22),+8 in more than 90% of metaphases with disappearance of all other abnormal chromosomes noted in the original sample. A tetraploid subline exhibiting duplication of most chromosomes, including the Ph, comprised the remaining metaphases. Upon further cultivation in vitro, the cells transformed spontaneously over a period of several weeks, from T-lymphoid into myeloid cells. Expression of CD7 was lost, but reactivities with monoclonal antibodies to CD34, CD33 and CD13 were newly acquired. The karyotype was hypertriploid and all cells carried two copies of t(9;22) and lacked normal copies of No. 9 or Y. The cells have since maintained stable cytogenetic and phenotypic profiles. Molecular rearrangement of the breakpoint cluster region was identified in the primary blasts and the established line and T-cell receptor gene rearrangements were not found. These observations suggest that the leukemic blast arose from primitive stem cells, not irreversibly committed T cells, and that these stem cells retained the capacity to differentiate along the myeloid pathway. PMID- 1625479 TI - In vitro suspension culture reactions to 1,25 dihydroxyvitamin D3 in relation to bone marrow morphology and prognosis in patients with myelodysplastic syndromes. AB - Thirty-four patients with MDS or AML following MDS were studied with regard to survival, peripheral blood values and bone marrow morphology. The effects of 1,25 dihydroxyvitamin D3 (D3) on differentiation (NBT positivity) and proliferation (3H-thymidine incorporation) were studied in suspension cultures of bone marrow cells. Twelve bone marrow donors served as controls. Normal cells showed spontaneous differentiation in vitro, but only 2/12 were induced to differentiation by D3. Myelodysplastic cells did not differentiate spontaneously, but cells from 18/34 patients differentiated after incubation with D3. Normal cells showed increased proliferation, myelodysplastic cells showed a heterogeneous response and leukemic cells reacted with decreased proliferation after D3 incubation. Poor survival was associated with low platelet counts, high percentage of bone marrow blasts (BM blast %), low spontaneous in vitro proliferation and absence of hypogranulation of myeloid cells. Platelet counts and hypogranulation retained their predictive value in a multi-variate analysis. Progression to AML was predicted by a high BM blast % and low scores for erythroid and total dysplasia. In conclusion, the pattern of in vitro proliferation showed prognostic value while the pattern of vitamin D3-induced differentiation failed to correlate to other parameters. An estimation of bone marrow dysplasia can be used to predict the development of AML. Our results add to the information about the biology of MDS and may be important for the evaluation of therapeutic trials. PMID- 1625480 TI - Four additional cases of trisomy 14 as the sole anomaly in various haematological malignancies. AB - We report on four cases of trisomy 14 as the sole anomaly. Three cases were myelodysplastic syndromes and one was a non-Hodgkin's lymphoma. This anomaly is mainly in myeloid disorders and still remains to be well documented. On the other hand, we show this anomaly to be also a non-random anomaly in lymphoproliferative disorders. PMID- 1625481 TI - Inversion of chromosome 3 (q21; q26) in a case of secondary acute leukaemia with thrombocythaemia. PMID- 1625482 TI - Sensitivity of flow cytometry. PMID- 1625483 TI - Bone marrow transplants for chronic lymphocytic leukaemia. PMID- 1625484 TI - SCL gene in human tumors. AB - The SCL gene encodes a member of the helix-loop-helix (HLH) family of transcription factors and is reportedly involved in up to 25% of T-cell acute lymphoblastic leukemia (T-ALL). We have surveyed over 120 primary human tumors including melanomas, myeloid, and lymphoid leukemias, and other solid tumors without evidence of rearrangements involving SCL. These results are further supported by low level expression of SCL in these tumors (as assessed by a polymerase chain-reaction-based method). We conclude that rearrangement/translocation with subsequent activation of SCL occurs infrequently in myeloid leukemias and melanomas. PMID- 1625485 TI - Comparison of the effects of all-trans and cis-retinoic acid on the blast stem cells of acute myeloblastic leukemia in culture. AB - Recent work has shown that acute promyelocytic leukemia (APL) cells have a characteristic translocation involving the retinoic acid receptor on chromosome 17 and the myl protein on chromosome 15. Patients with APL respond to the administration of all-trans-retinoic acid. A cell line with t15;17 (NB4) has recently been reported; this line responds to all-trans-retinoic acid with differentiation. There is also a recent report showing that all-trans-retinoic acid is more active than cis-retinoic acid in inducing differentiation in freshly obtained APL cells. All-trans-retinoic and cis-retinoic acid are compared for their effects on growth in culture of freshly obtained AML cells, cell lines without t15;17, and NB4 cells. While all of these AML populations responded to both forms of retinoic acid, NB4 cells only were much more sensitive to all-trans retinoic acid compared to cis-retinoic acid. The difference was seen when the NB4 cells were exposed in suspension and not when colony-formation in methylcellulose was used as an end point. Both forms of retinoic acid increased the sensitivity of blast cells to cytosine arabinoside; for NB4 cells, the sensitization was much greater when all-trans-retinoic acid was used rather than cis-retinoic acid. We conclude that the increased effects of all-trans-retinoic acid are specific for APL cells, and that a major effect of retinoic acid is on blast stem cell self renewal. PMID- 1625486 TI - B-chronic lymphocytic leukemia cells contain both endogenous kappa immunoglobulin mRNA and critical immunoglobulin gene activation transcription factors. AB - B-cell chronic lymphocytic leukemia (B-CLL) is a hematologic malignancy characterized by the proliferation and accumulation of mature-looking B lymphocytes. Patients with B-CLL exhibit a number of immune defects including: auto-antibodies, depressed cell-mediated immunity and hypogammaglobulinemia (HG). We investigated the control of Ig production in the malignant CLL B-cell at a transcriptional and translation level. We isolated fresh leukemic B-cells from CLL patients and analyzed for the presence of nuclear factors OCT-1, OCT-2, and NF-KB. Malignant B-cells were purified to greater than 90% B-cells, and total cellular RNA and nuclear proteins were isolated from these cells. Mobility shift assays were probed with 32P-labeled oligonucleotides specific to the immunoglobulin (Ig) enhancer and promotor regions. We detected endogenous OCT-1, OCT-2, and NF-KB in all patients tested (n = 5). We then evaluated whether activation of CLL B cells could augment kappa-mRNA levels. CLL cells (n = 3) exposed to phorbol ester and A23187 were harvested at 0, 2, 4, 8, and 48 min and examined for kappa-mRNA by Northern blot. All CLL patients (n = 3) had easily detectable levels of endogenous kappa-mRNA. However, only one patient had an obvious increase in kappa-mRNA post-induction with TPA/A23187. There was no concomitant increase in this patient's OCT-1, OCT-2, or NF-KB level. This finding prompted us to survey other B-CLL patients (n = 6) for Ig nuclear transcriptional factors pre- and post-induction. In summary, CLL B cells express Ig transcriptional factor OCT-1, OCT-2, and NF-KB constitutively. The endogenous level of NF-KB may account for the basal kappa-mRNA detected in B-CLL cells. However, the inability to augment NF-KB levels may, in part, explain the low levels of Ig synthesis in CLL B-cells. PMID- 1625488 TI - Partial characterization of a familial B lymphosarcoma with a thymic localization in cattle. AB - We recently described an original epidemiological form of bovine leukosis in cattle. In the young female offspring of one bull, more than 3% of animals developed a thymic lymphoblastic lymphosarcoma. Of these, 31 cases, together with a lymphoid cell line established from one of the tumours, were phenotypically characterized. Characterization was done using a large combination of well clustered monoclonal antibodies, and monoclonal antibodies prepared in our laboratory by immunizing mice either with bovine normal lymphocytes or with tumour thymic cells. The thymic tumours and the cell line did not express any T lymphoid antigens but they did express some B lymphoid markers. The phenotype of the tumour cells was CD45+/-, CD44+/- TdT+, class II-DR+/-, CD19+/-, CD21-, Ig- and HBM 57+ (recognizing the mb-1 chains of the B-cell receptor). The cell line expressed a more mature phenotype: TdT-, CD45-, CD44+, class II-DR+, CD19+, CD21+/- and sIgG+. These results allow us to consider these tumours as B-cell derived. These B lymphosarcomas with a thymic localization are reminiscent of a human mediastinal non-lymphoblastic lymphoma reported as a primary mediastinal clear cell lymphoma. The possibility of a thymic or extrathymic origin for this B lymphosarcoma is discussed. PMID- 1625487 TI - Initiation and promotion in radiation-induced myeloid leukemia. AB - Acute myelomonocytic leukemia develops in 10-30% of irradiated (300 rad) SJL/J mice, after a lag period of around one year. Additional treatment with dexamethasone shortly after irradiation increased leukemia incidence up to 50%. Experiments were conducted in order to demonstrate the existence of preleukemic cells in irradiated mice and to explore the possible role of dexamethasone, cyclophosphamide, and different hemopoietic growth factors on their promotion to overt leukemia. Transplantation of bone marrow cells from mice exposed to 300 rad plus dexamethasone into appropriate recipients, performed 4-5 months after leukemogenic treatment, resulted in acute myeloid leukemia (AML) development of donor origin in 70% of the recipients. Transfer of fractionated preleukemic bone marrow showed that the highest AML incidence developed in the recipients of fractions enriched in early hemopoietic precursors. The promoting effect of dexamethasone on preleukemic cells was confirmed by demonstrating its similar coleukemogenic effect whether administered within several hours or 130 days after radiation. Treatment with cyclophosphamide shortly after radiation could not replace the dexamethasone effect but was found to be complementary to the coleukemogenic effect of dexamethasone. Early administration of hemopoietic growth factors (starting 14 days after radiation and dexamethasone) showed that colony-stimulating factor (CSF) 1 increased the AML incidence (75%) and reduced its latency. Treatment with recombinant granulocyte-CSF (rG-CSF) had a reduced effect and recombinant granulocyte-macrophage CSF (rGM-CSF) had no promoting effect. However, administration of different factors several months after the leukemogenic treatment revealed that rGM-CSF increased AML incidence (75%) and shortened its latency, whereas rG-CSF and CSF-1 had no effect. In contrast, the late administration of recombinant interleukin 6 reduced AML incidence significantly (23%). The present results indicate that murine radiation induced AML is a multiphase process involving radiation induced preleukemia that can be promoted by different treatments. PMID- 1625489 TI - The non-random dic(9;12) translocation in acute lymphoblastic leukemia is associated with B-progenitor phenotype and an excellent prognosis. AB - A dicentric translocation involving the short arms (p) of chromosomes 9 and 12 was identified in 15 of 2303 successfully banded cases of acute lymphoblastic leukemia (ALL) in children, consecutively entered on protocols of the Pediatric Oncology Group (1986-1990) or St Jude Children's Research Hospital (1984 and 1990). The dic(9;12)(p1?1;p1?2) was seen only in patients with a B progenitor cell immunophenotype: the frequency was 0.8% among pre-B cases (4/508) and 0.9% (11/1177) among early pre-B cases. Laboratory and clinical characteristics were similar to those of the general population of children with ALL, with the exception of a marked male preponderance (12/15 cases). Flow cytometric studies revealed a leukemic cell DNA index of 1.0 in all cases. All fifteen patients are in continuous complete remission at a median follow-up duration of 57+ months (range 9-93+ months). These findings suggest that the dic(9;12) is a recurrent chromosomal translocation in pediatric ALL, occurs exclusively in B-progenitor ALL, and unlike other non-random translocations, is associated with an excellent prognosis. PMID- 1625490 TI - Late intensification with POMP chemotherapy prolongs survival in acute myelogenous leukemia--results of a Southwest Oncology Group study of rubidazone versus adriamycin for remission induction, prophylactic intrathecal therapy, late intensification, and levamisole maintenance. AB - Between August 1978 and September 1982, 642 patients with newly diagnosed acute myelogenous leukemia (AML) were entered onto a Southwest Oncology Group Study which addressed four questions. (i) What is the comparative utility of rubidazone versus adriamycin in remission induction? (ii) What is the role of prophylactic intrathecal therapy in AML? (iii) Does late intensification affect treatment outcome? (iv) Does maintenance with levamisole affect disease-free survival or overall survival? Among 611 evaluable patients, 329 (54%) achieved complete remission. There was no difference in the remission rate between those patients receiving rubidazone (54%) and those receiving adriamycin (54%) as part of the induction regimen. Prophylactic intrathecal therapy with cytosine arabinoside had no effect on the incidence of central nervous system disease or survival. After nine months of complete remission, patients were randomized between late intensification with POMP (mercaptopurine + vincristine + methotrexate + prednisone) or continued maintenance with OAP (vincristine + cytosine arabinoside + prednisone). T patients randomized to late intensification had better survival and disease-free survival, compared to those randomized to receive no late intensification (p = 0.027 and 0.030, respectively). At twelve months of remission, surviving patients were randomized to receive levamisole or no further treatment. There was no evidence that levamisole affected survival or disease free survival. PMID- 1625491 TI - Cytogenetic analysis of hemopoietic peripheral blood cells collected by leukapheresis after intensive chemotherapy in advanced phase Philadelphia positive chronic myelogenous leukemia. AB - Peripheral hemopoietic blood cells previously collected by leukapheresis were reinfused in advanced phase Philadelphia (Ph)-positive chronic myelogenous leukemic patients to promote the recovery of bone marrow function after intensive radiochemotherapy. Cytogenetic analysis was performed on these cells, induced to proliferate and to be mobilized by a first administration of marrow toxic drugs and collected when the white blood cell count was very low. In five patients only Ph-negative apparently normal cells were found. In five cases different proportions of Ph+/Ph- cells were observed and in the remaining five cases only Ph+ cells were present. Chromosomal abnormalities other than Ph, not detected in the cytogenetic analysis performed on bone marrow cells before chemotherapy treatment, were found in five cases. These findings confirm that Ph- cells can persist in the marrow of Ph+ patients in the advanced phase of disease and indicate that a high percentage of leukemic cells retain karyotype evolution not detectable using standard drawing and culture techniques. PMID- 1625492 TI - Cost of complete remission induction in acute myeloblastic leukemia: evaluation of the cost-effectiveness of a new drug. AB - The use of new drugs in the treatment of AML could dramatically increase the cost of induction chemotherapy. To evaluate the cost-effectiveness of such new drugs, the overall cost to achieve complete remission (CR) with treatments including these drugs has to be compared to the cost of the daunorubicin-cytosine arabinoside (DNR-AraC) association, considered as the reference treatment. A retrospective analysis of charts from 15 patients treated with DNR-AraC was used to identify 228 items of cost, including general cost, diagnostic, supportive care, and chemotherapy. Eleven patients underwent CR after one course of chemotherapy for a cost of US$16,701 +/- 4451, and four patients achieved CR after two courses for a cost of US$37,130 +/- 4923. The chemotherapy represented only 1.4% of the total cost, supportive care 25% and general cost 56%. According to these data, the projective cost of a treatment with mitoxantrone instead of DNR was simulated in 40 untreated patients with AML. The better rate of CR obtained after one course of chemotherapy leads to a saving of 9% (US$1261) per patient, despite the higher cost of chemotherapy. Cost-effectiveness evaluation should be included in the clinical study of trials with new drugs. PMID- 1625493 TI - Molecular analysis of Philadelphia-positive childhood chronic myeloid leukemia. AB - The breakpoints in chromosome 22 were determined in five children with Philadelphia-positive chronic myeloid leukemia. All had rearrangements within the major breakpoint cluster region (M-bcr). Four patients had breakpoints in the 5' region of M-bcr (zones 1-3), whereas one had a rearrangement in the 3' region (zone 4). The patient with the 3' rearrangement was the only one to develop a lymphoid blast crisis; he also had a substantially longer survival (102 months) than the others (11-54 months). PMID- 1625494 TI - Selective toxicity of ethacrynic acid towards lymphocytes of chronic lymphocytic leukemia in vitro. AB - We have used the MTT colorimetric assay to determine the sensitivity to ethacrynic acid of lymphocytes from normal donors and of peripheral blood cells from leukaemia patients. Whereas normal lymphocytes and cells from acute or chronic myeloid leukaemia showed similar sensitivities (median inhibitory dose, ID50 = 20-22 microM), lymphocytes from chronic lymphocytic leukaemia patients were much more sensitive (ID50 = 6 microM). This result was found irrespective of the assay duration. PMID- 1625495 TI - Haematopoietic stem cell lines activate novel enhancer-dependent expression of reporter DNA immediately after transfection by mechanisms involving interleukin 3 and protein kinase C. AB - Approaches to analysing gene regulation in haematopoietic stem cells are limited by their low concentration and rapid cell death outside of a trophic marrow environment. We have used interleukin 3 (IL3)-dependent cell lines as stem-cell models to investigate gene regulation during signal transduction by growth factors. We report that expression of the bacterial chloramphenicol acetyl transferase reporter gene linked via the weak thymidine kinase promoter to known upstream enhancer regions required for expression of the proliferation-dependent proto-oncogene c-fos occurs almost immediately (within 2 h) after transfection. Expression is stimulated by IL3 or activation of protein kinase C. Our findings indicate that IL3-dependent cell lines possess an extremely rapid transcription mechanism for introduced DNA, which if also present in normal cells may be usefully used to analyse gene regulation during signal transduction leading to growth and differentiation by haematopoietic growth factors. PMID- 1625496 TI - Serum monocyte colony-stimulating factor, erythropoietin and interleukin-6 in relation to pancytopenia in hairy cell leukemia. AB - In patients with hairy cell leukemia (HCL), we measured serum levels of monocyte colony-stimulating factor (M-CSF), interleukin-6 (IL-6), and erythropoietin during various degrees of pancytopenia characteristic for this disease. Serial sera from 12 HCL patients during various stages of the disease were analyzed. No correlation was found between the levels of M-CSF or IL-6 and the numbers of circulating monocytes or platelets, normal values of M-CSF (4 to 10 mg/l), and IL 6 (3-50 U/ml) being detected during all stages of the disease. In contrast, erythropoietin levels were inversely related with the hemoglobin concentration (r = -0.79), indicating the presence of a normal feedback mechanism for this factor in patients with HCL. PMID- 1625497 TI - Transient cytogenetic relapse in a Ph1-positive chronic myelogenous leukemia patient previously treated with alpha-interferon. AB - Therapy with alpha-interferon (IFN alpha) can suppress the Ph1-positive hemopoiesis in a percentage of patients with chronic myelogenous leukemia (CML). We used IFN alpha to treat a 30-year-old CML patient, characterized by favourable prognostic signs (such as low leukocytosis, absence of splenomegaly and no increase in bone marrow blasts) at diagnosis, and obtained a complete remission, as evaluated by Southern blot and cytogenetic analysis, after one year of treatment. However, the polymerase chain reaction (PCR) revealed the persistence of a minimal residual disease. The IFN alpha therapy was stopped and the hematological status remained stable until eighteen months later, when a cytogenetic analysis revealed the appearance of a clone characterized by t(9;22) and trisomy 8, accounting for 30% of bone marrow metaphases. This cell population spontaneously regressed in the following months, before any cytotoxic treatment. However, as leukemic cells, detected by PCR, were still present, the patient received a high dose chemotherapy, which induced the complete eradication of the Ph1-positive clone, as demonstrated by the absence of bcr-abl transcript at the PCR reaction. Molecular and cytogenetic remission persist one year later, without any further therapy. PMID- 1625499 TI - Early afterdepolarization in myocardium and its clinical implications. PMID- 1625498 TI - Monosomy 7 and unbalanced t(1;7) in an adolescent boy with myelodysplastic syndrome. AB - Monosomy 7 occurs in approximately 5% of cases of myelodysplastic syndrome (MDS) in children and is associated with a poor prognosis. The unbalanced translocation t(1;7) is common in therapy-related MDS in adults but is extremely rare in children, with only three cases reported to date. We describe a pediatric case of MDS with the unusual combination of monosomy 7 and unbalanced t(1;7) in two distinct clones. Both clones were detected at diagnosis and have persisted throughout the course of MDS in this patient, a 16-year-old boy without prior exposure to known mutagens. Because of recurrent severe infections associated with neutropenia, he was treated with recombinant human granulocyte-macrophage colony-stimulating factor. This therapy improved the neutrophil count but did not alter the karyotype or the progression of disease. PMID- 1625500 TI - Time-dependence of inducible ventricular tachycardia in a chronic canine model. AB - The natural history of inducible ventricular tachycardia in post-infarction dogs was followed with serial programmed electrical stimulation (PES: 1-3 extrastimuli, 4 msec duration, 2 x diastolic threshold). Arrhythmia inducibility was defined as a minimum of four unstimulated ventricular ectopic beats. Of 119 dogs prepared for chronic electrophysiological study, 87 (73.1%) were ambulant 24 hours after surgery. Mean infarct size was 11.1 +/- 1.5% of left ventricular (LV) mass for animals dying in the first week, before stimulation. 92.4% of 66 animals were inducible when stimulated at one week, 66.7% at two weeks and 64.3% and 55.6% at the third and fourth weeks respectively (p less than 0.01, Chi-square analysis). Infarct sizes fell from 7.0 +/- 0.5% LV mass at first stimulation to 4.6 +/- 0.8% at third stimulation and could not be visualized thereafter (p less than 0.01,ANOVA). There was no statistical difference between infarct sizes for inducible and non-inducible animals, but in both cases infarcts were smaller (p less than 0.01) than for those animals which died suddenly during the first week. This time-dependent decrease in arrhythmia inducibility, which may be related to infarct size, should be considered when similar models are employed for chronic electrophysiological studies. PMID- 1625501 TI - Effect of a new antiarrhythmic BK 129 on canine vascular smooth muscle in vitro. AB - The effect of a new carbanilate derivative BK 129, 1-methoxymethyl-2(1 perhydroazepinyl)ethyl ester 2-(n)-pentyloxycarbanilic acid hydrochloride, was tested on preparations of canine dorsal pedal and coronary artery in vitro. The drug produced relaxation of arterial rings both under resting conditions and under precontraction with KCl. BK 129, at a concentration of 10(-5) mol/l, produced a shift to the right of the concentration-response curve of phenylephrine, with a decrease in the slope and a depression of the maximal response. BK 129 inhibited the response to norepinephrine and blocked histamine- and norepinephrine-induced contractions in Ca(2+)-free physiological salt solution. The electrical stimulation-induced contractions of arterial preparation were also inhibited. BK 129 shifted the concentration-response curve of CaCl2 in Ca(2+)-free depolarizing solution to the right in a non-competitive manner. It may be concluded that BK 129 is a local anesthetic which possesses relaxant properties. It appears to inhibit Ca2+ entry into the smooth muscle cell and Ca2+ release from sarcoplasmic reticulum. PMID- 1625502 TI - Selectivity of a CaCl2 continuous infusion screening method in rats. AB - In albino rats the combined use of two methods based on a continuous perfusion of aconitine nitrate (0.15 mg/ml) or calcium chloride (0.4 M) demonstrated the selectivity of the calcium chloride-induced dysrhythmias model. This rapid screening was carried out with antidysrhythmic agents according to the Vaughan Williams's classification (1): quinidine (class I) 5 mg/kg; atenolol (class II) 2 mg/kg; amiodarone (class III) 10 mg/kg and verapamil (class IV) 2 mg/kg. A compound synthesized in our laboratory was used to verify model selectivity. PMID- 1625503 TI - Effects of amiodarone on the pharmacokinetics and toxicity of digoxin in laboratory animals. AB - Some pharmacokinetic interactions between digoxin and amiodarone were studied in experiments on rabbits. An increase of digoxin serum levels was established in amiodarone-treated rabbits (amiodarone 30 mg/kg s.c. for five days alone or together with digoxin). The calculated elimination half-life (t 1/2) and the area under the curve (AUC) of digoxin were increased and the digoxin clearance was decreased, being most pronounced in animals receiving amiodarone-digoxin combination for five days. There were no changes either in digoxin toxicity in amiodarone-treated guinea pigs or in serum levels of T4, T3 and TTH. The possible mechanisms of digoxin-amiodarone interactions are discussed. PMID- 1625504 TI - Omeprazole-induced changes in gastric mucus secretion. AB - The influence of omeprazole treatment on gastric mucus secretion in man was examined in two separate studies. 24 outpatients with endoscopic duodenitis but normal gastric mucosa were treated under double-blind conditions with either omeprazole 20 mg o.m. or placebo for four weeks. Omeprazole was found to induce a significant reduction (p less than 0.001) in the amount of neutral and total mucoproteins into the gastric juice and in the viscous and protective properties of mucus as assessed by a Mucoprotective Index. In a subsequent study 12 omeprazole-treated patients were re-examined either 10 days (6 patients) or 15 days (6 patients) after the drug withdrawal. A trend towards normalization of mucus secretion was detectable already after 10 days, but only at 15 days did gastric mucus fully revert to normal. The results suggest that the decrease in the quantity and quality of mucus secretion observed with omeprazole is a transient phenomenon, secondary to the sustained acid suppression induced by the drug and clinically irrelevant. PMID- 1625505 TI - Dialysability of dimethindene maleate (Fenistil) from blood after intravenous injection. AB - Dimethindene, an antihistaminic drug, is the treatment of choice in dialysis patients suffering from skin itching. During hemodialysis procedures not only toxic metabolites, but also drugs are extracted from plasma. To answer the question if dimethindene is dialyzable from plasma, three healthy male volunteers received 4 mg of dimethindene solution intravenously. Ten minutes later 100 ml cubital vein blood was taken and 25,000 I.E. Liquemine was added. Plasma was separated and pumped through a cuprophan hollow fiber dialyzing module with an effective surface of 35 cm2. In periods of ten minutes samples of plasma and dialysate were taken to analyze their dimetindene concentrations. A mean clearance of 38 ml/min*m2, SD 10.2 and coefficient of variation [%] 26.8 was found. This is comparable to the well known clearance of theophylline, so it can be considered that dimethindene is eliminated from plasma during hemodialysis procedures. PMID- 1625506 TI - Intracerebroventricular endothelin-1 (ET-1) produces Ca(2+)-mediated antinociception in mice. AB - Intracerebroventricular (i.c.v.) administration of endothelin-1 (ET-1) at doses of 0.313, 0.625, 1.25, 2.5 and 5 pmol/mouse produced a strong antinociceptive effect as evaluated by hot plate method in mice. The effect was dose-dependent and lasted for more than 120 min. The opioid receptor antagonist naloxone did not antagonize, and the cyclooxygenase inhibitors indomethacin and diclofenac slightly inhibited the ET-1 effect. The calcium overload blocker cinnarizine antagonized the antinociceptive effect of ET-1, suggesting that the ET-1 effect might be Ca(2+)-mediated. PMID- 1625507 TI - [Comparative studies of preventive antibiotic administration in ERCP]. AB - In a nonblind nonrandomized clinical trial two groups of patients who were undergoing ERCP - A (n = 182) with antibiotic prophylaxis and B (n = 220) without an antibiotic--were compared on a prospective basis. The efficacy of properly timed prophylaxis with a therapeutically effective antibiotic had previously been established by a pilot study and a definitive trial based on HPLC assays of endoscopic biopsy specimens taken from the duodenal papilla. In Group A (n = 182) there was hyperamylasaemia without a leucocytic reaction in only 18 (14.75%) of the ERP patients and two (3.33%) of the ERC patients, but in Group B (no antibiotic - n = 220) this change was detected in 48 (35.29%) of the ERP patients and 12 (14.28%) of the ERC patients (P = 0.00018 and 0.043 respectively). Hyperamylasaemia with a leucocytic reaction occurred in only one patient with ERP from Group A (0.82%) as compared with 15 patients (11.02%) from the untreated group (P = 0.00047). These results were highly significant. There were three cases of subclinical pancreatitis and two of acute pancreatitis--all of them in the control group. Although these results were not statistically significant (because the number of cases was too small), they are clearly consistent with the growing tendency towards using antibiotic cover. On the basis of these results we regard antibiotic prophylaxis during ERCP as a sensible precaution, and in patients with any concurrent disease which heightens the risk it is essential. PMID- 1625508 TI - [Preoperative hemodilution before elective resections of colorectal cancers for sparing homologous blood transfusion]. AB - The records of 389 patients following elective resection of colorectal carcinoma were analysed in order to examine perioperative transfusion. Preoperative hemoglobin levels of 12.8 g/dl in women and 14.2 g/dl in men were found (p less than 0.01). Only 11% of the patients had an anemia. Increasing age and sex had both a significant relation to decreasing preoperative hemoglobin level and higher frequency of transfusion (p less than 0.01). Women got perioperative more often blood transfusion (84.4%). On an average 2.1 units of blood were transfused. There were no relation to tumor stage or tumor location be found (p greater than 0.01). 48.8% of the patients had attendant diseases. Cardiac insufficiency and pulmonary diseases became more frequent. Excluding all patients with contraindication to preoperative hemodilution it was possible to do preoperative hemodilution by 61.2% of the patients. In conclusion preoperative hemodilution should be done before elective resection of colorectal cancer if there was no contraindications to reduce the number of autologous blood transfusion. PMID- 1625509 TI - [Improved treatment results in advanced gallbladder and bile duct cancer by postoperative combined radiotherapy]. AB - From 1984 to 1990 38 patients had an operation for carcinoma of the gallbladder and bile ducts. The unfavorable prognosis of this type of cancer was improved by a combined treatment, consisting of surgical tumor reduction and implantation of a transhepatic drainage, followed by external radiation and intracatheter brachytherapy. Nine patients were treated in this manner, seven died 6-67 months after operation, two are still alive 7 and 13 months postoperatively. PMID- 1625510 TI - [Chronic reflux esophagitis with endobrachyesophagus and multifocal adenocarcinoma]. AB - In approximately 10% of all cases of endobrachesophagus a malignant degeneration occurs. A frequent endoscopic and bioptic control of the endobrachesophagus is the prognostic decision in order for a developing adenocarcinom to be identified in the early stages. Our casuistry demonstrates the problematic nature of the diagnostic and therapy of a multifocal adenocarcinom in an endobrachesophagus. PMID- 1625511 TI - [Endometriosis of the terminal ileum--differential diagnosis of Crohn disease]. AB - Ileocecal resection was performed in two female patients with stenosis of the terminal ileum. Histological findings confirmed the clinical diagnosis of Crohn's disease in the first case, although focal intestinal endometriosis was detected. The resection specimens of the other patient exclusively showed lesions of endometriosis extending from the subserosa to the mucosal tissue. Typical lesions of Crohn's disease were totally absent in this case. Although not very frequent, endometriosis is an important differential diagnosis of Crohn's disease in young females. PMID- 1625512 TI - [Helicobacter pylori spectrum: from gastritis to malignancy]. PMID- 1625513 TI - [Risk of cancer in chronic inflammatory bowel diseases]. AB - This article summarizes the data concerning cancer risk in chronic inflammatory bowel disease. Cancer risk of ulcerative colitis and Crohn's disease is highly dependent on the duration of the disease, extent of bowel inflammation, and probably also of the age at onset of the disease. Cancer development follows the dysplasia-carcinoma-sequence. Diagnosis of premalignant changes is the basis for follow-up studies in ulcerative colitis as suggested here. PMID- 1625514 TI - Pro- and anti-inflammatory properties of human recombinant IL-1 beta during experimental arthritis in rats: 1. Dependence on dose and severity threshold. AB - The effects of human recombinant interleukin-1 beta (HrIL-1 beta) were investigated in arthritic rats sensitized with type II collagen (CII) and muramyl dipeptide (MDP). When administered subcutaneously (sc) daily during established arthritis, low (0.02 micrograms) and medium (0.2 micrograms) HrIL-1 beta doses exerted paradoxical beneficial properties on paws with moderate and severe inflammation, respectively. In contrast, the highest dose (2 micrograms) had a pejorative effect on developing arthritis. In addition, HrIL-1 beta attenuated paw volume and deterioration of the joints as assessed radiologically. Hence, paw inflammation response to IL-1 exposure depended on the dosage and the severity of previous arthritis prior to the IL-1 challenge. Some of these paradoxical activities may be due to the capacity of IL-1 to induce its own inhibitors or feedback loops thus counterbalancing its phlogistic properties. PMID- 1625515 TI - Failure of the gamma-aminobutyric acid (GABA) derivative, baclofen, to stimulate growth hormone secretion in heroin addicts. AB - In order to establish possible alterations in the gamma aminobutyric acid (GABA)ergic control of growth hormone (GH) secretion in heroin addicts, ten patients (age, 25.8 +/- 1.07 yr (mean +/- SE); duration of heroin addiction, range 3-8 yr; weight, 67.3 +/- 0.87 kg body weight), and ten age (29.1 +/- 0.84 yr)- and weight (69.7 +/- 0.87 kg)-matched normal controls were tested with the GABAergic B-receptor agonist baclofen (10 mg p.o. at 09.00 h) (experimental test) or a placebo (control test). Blood samples for GH assay were taken every 15 min for the next 150 min. Normal controls underwent one control and one experimental test. Heroin addicts were submitted to both baclofen and placebo test twice, once around the time of their admission to a recovery community for drug abusers, when they were still assuming heroin, and again after two months of permanence in the community. From the time of their admission to the community, the patients were forbidden to use heroin. For two weeks after admission they were treated with clonidine and acetylsalicilic acid to attenuate withdrawal symptoms. Thereafter, the patients underwent a period of wash-out of pharmacological treatments for at least 6 weeks before being retested. Basal GH levels were similar in normal controls and heroin addicts in all tests and remained unmodified during control tests in all subjects. The administration of baclofen increased four times the serum GH levels within 120 minutes in the normal controls, whereas it did not modify serum GH concentrations in heroin addicts either during the period of drug abuse or after two months of abstinence. These data show that the control of GH secretion mediated by GABAergic B-receptors is impaired in heroin addicts. It is hypothesized that this neuroendocrine alteration might represent a trait marker of heroin addiction, or more likely, that it was a consequence of a long addiction to heroin persisting after two months of abstinence. PMID- 1625516 TI - Recombinant human superoxide dismutase can attenuate ischemic neuronal damage in gerbils. AB - The effects of recombinant human superoxide dismutase (r-hSOD) on ischemic neuronal injury were examined. Cerebral ischemia was produced in Mongolian gerbils by occluding bilateral common carotid arteries for 5 min. Preischemic treatment with r-hSOD clearly reduced hippocampal neuronal damages while postischemic treatment did not. This result suggests that oxygen free radicals play an important role in selective vulnerability to ischemia and r-hSOD has a potential clinical usefulness against cerebral ischemia. PMID- 1625517 TI - One brief exposure to a psychological stressor induces long-lasting, time dependent sensitization of both the cataleptic and neurochemical responses to haloperidol. AB - Rats were exposed for 10 minutes to one of several enclosures graded in novelty. In one experiment they were then simply sacrificed and plasma corticosterone determinations made in order to obtain an index of the relative stressfulness of these enclosures. In a second experiment the animals received haloperidol and were tested for catalepsy, 2 hours or two weeks following the novel experience. The most novel experience, exposure to a black box, resulted in the highest corticosterone levels and was the only one of our pre-treatments to induce significant enhancement of catalepsy as well as alteration of nucleus accumbens dopamine levels, 2 weeks--but not 2 hours--later. These findings indicate that brief exposure of adult animals to a psychological stressor can induce a long term alteration in both behavioral and neurochemical responses to a drug and that this effect requires a minimum level of stress to get started and once triggered gets stronger with the passage of time. PMID- 1625518 TI - Effects of vinconate on spatial learning impairments induced by medial septal lesion in rats. AB - We investigated the effects of vinconate, a novel vinca alkaloid, on spatial learning deficits induced by medial septal (MS) lesion in rats. MS lesion was produced by passing an anodal DC current. In vehicle-treated MS-lesioned rats impairment of spatial learning was observed, shown by a decrease in correct choices and an increase in total errors during training in a radial arm maze task. Vinconate (10 mg/kg) treatment alleviated the decrease in correct choices and the increase in total errors induced by MS lesion. Vinconate (5 and 10 mg/kg) treatment showed a tendency to reverse the decrease in choline acetyltransferase activity in the hippocampus caused by MS lesion. The present study suggests that vinconate has an anti-amnesic effect on MS lesion-induced amnesia by ameliorating the dysfunction in cholinergic (ACh) neurons. PMID- 1625519 TI - The effect of opiate agonists and antagonists on Na(+)-Ca2+ exchange in cardiac sarcolemma vesicles. AB - Opiate agonists and antagonists inhibit Na(+)-Ca2+ exchange in the isolated cardiac sarcolemma vesicles. Non-opioid stereoisomers (dextrorphan, Mr 1542MS, WIN 44,441-3) display effects similar to their opioid isomers (levorphanol, Mr 1543MS, WIN 44,441-2) suggesting that inhibition is not mediated by opiate receptors. Naloxone (permeable) and methylnaloxone (impermeable) inhibit the Na(+)-Ca2+ exchange similarly, suggesting an extravesicular location of inhibitory site. The inhibitory potency of naloxone is pH-independent in the range of 7.4-9.1, suggesting that the charge-carrying properties of drug-protein interactions are not altered under the tested conditions. Opiates display similar dose-response relationships for Na(+)-Ca2+ exchange and its partial reaction, the Ca(2+)-Ca2+ exchange. The opiate-induced inhibition is complete and noncompetitive in regard to extravesicular calcium. These data suggest that opiates do not bind to the Ca(2+)-binding domain (A-site), but they may interest either with the Na(+)-binding site (B-site) or with a putative opiate-binding site, presumably located outside of the ion-binding vicinity. Further studies on structure-activity relationship might lead to the discovery of potent and more specific inhibitors of cardiac Na(+)-Ca2+ exchanger. A possible relevance of these findings to some non-opioid pharmacological effects of naloxone on the cardiac muscle is suggested. PMID- 1625520 TI - Arginine-vasopressin fragment 4-9 stimulates the acetylcholine release in hippocampus of freely-moving rats. AB - We examined the effects of arginine-vasopressin (AVP) C-terminal fragment 4-9, which facilitates learning and memory, on the extracellular acetylcholine (ACh) release in hippocampus of freely-moving rats using the microdialysis technique. Following administration of AVP4-9, p-Glu-Asn-Cys[Cys]-Pro-Arg-Gly-NH2, through the dialysis probe into the hippocampus, ACh levels in dialysates from the hippocampus increased markedly in dose and time dependent manner at 2-2.5 and 2.5 3 hr. AVP1-9, the parent peptide, has a similar enhancing effect on ACh release as AVP4-9. Stimulated ACh release by AVP4-9 was significantly inhibited by V1 selective receptor antagonist ([1-(beta-mercapto-beta,beta cyclopentamethylenepropionic acid), 2-(O-methyl)-tyrosine]AVP), but not by V2 selective antagonist ([1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-D-Ile, 4-Ile]AVP). From these observations, it is demonstrated that AVP4 9 stimulates the ACh release in rat hippocampus via mediating V1-like vasopressin receptors. PMID- 1625521 TI - Effects of haloperidol and prolactin secreting tumors on cerebrospinal fluid concentrations of prolactin in the female rat. AB - Studies were conducted to determine the effects of acute and chronic elevations in prolactin (PRL) secretion on serum and cerebrospinal fluid (CSF) PRL concentrations in the female rat. Young female rats showed a dose-dependent increase in serum and CSF PRL in response to haloperidol. A time-course evaluation of serum and CSF PRL levels after haloperidol indicated that serum PRL concentrations increased markedly by 30 min and declined thereafter; while CSF PRL increased more slowly, peaking at 2 to 8 h. In young rats with basal serum PRL levels, CSF PRL was maintained at 0.8 to 2.1% of serum PRL levels. During acute hyperprolactinemia, the CSF to serum PRL ratio increased to about 4%. During chronic severe hyperprolactinemia, induced by the growth of a MtT.W15 tumor, CSF PRL concentrations increased to 75 ng/ml, but this represented only 1.5% of serum PRL concentrations. Collectively, these data indicate that the blood-brain barrier effectively limits access to the brain of circulating PRL. PMID- 1625522 TI - Quantitative analysis of platelet-activating factor in rat brain. AB - Age-related decrease of the platelet-activating factor (PAF) content in rat brain was shown by a convenient method consisting of solid extraction of lipids with a Sep-Pak C-18 cartridge, lipid separation by HPLC and bioassay on rabbit platelets. This method was sufficiently sensitive to allow measurement of PAF in a single brain, and the recovery of PAF was quite high throughout the procedure. PMID- 1625523 TI - Effect of contraceptive treatment on thymic glucocorticoid receptors and hepatic microsomal enzyme system of adult rats. AB - Contraceptive steroid treatment accounted for about a 30 per cent decrease in the number of thymic glucocorticoid receptors of adult rats. Neonatal allylestrenol treatment had no influence on that treatment. The activity of the hepatic microsomal (PSMO) enzyme system was not changed by the contraceptive treatment. It appears that contraceptive treatment may account for overlaps on receptors in adulthood. PMID- 1625524 TI - The 5,7-DHT-induced anticonflict effect is dependent on intact adrenocortical function. AB - We have recently reported that the anxiolytic-like effect observed in rats severely depleted of brain serotonin (5-HT) by means of 5,7-DHT is indirect and probably involves the GABA(A)/benzodiazepine chloride ionophore receptor complex (GABAA/BDZ-RC). One tentative explanation for this effect considered the involvement of corticosteroids. In the present series of experiments we have therefore investigated the effect of adrenalectomy (ADX) on the 5,7-DHT-induced anxiolytic-like effect displayed by rats in Vogel's conflict test. ADX totally abolished the anticonflict effect of the 5,7-DHT lesion. Replacement treatment with corticosterone, but not with dexamethasone, reinstated the anticonflict effect. These results indicate that an intact adrenocortical function, possibly via brain steroid type I receptors, is required for the expression of the 5,7-DHT induced anxiolytic-like effect. It is postulated that ADX lowers the concentration of endogenous positive modulators at the GABAA/BDZ-RC to a level no longer sufficient to produce anxiolytic-like effects in 5,7-DHT-lesioned animals. The finding that 5,7-DHT-lesioned animals were more sensitive than sham-lesioned controls to the anticonflict effect of the barbiturate-like corticosteroid THDOC provides further support for the contention that an increased endogenous activity at the GABAA/BDZ-RCes is involved in the anxiolytic-like effect observed in rats with a severe depletion of brain 5-HT. PMID- 1625525 TI - High affinity acylating antagonists for muscarinic receptors. AB - The muscarinic antagonists pirenzepine and telenzepine were derivatized as alkylamino derivatives at a site on the molecules corresponding to a region of bulk tolerance in receptor binding. The distal primary amino groups were coupled to the cross-linking reagent meta-phenylene diisothiocyanate, resulting in two isothiocyanate derivatives that were found to inhibit muscarinic receptors irreversibly and in a dose-dependent fashion. Preincubation of rat forebrain membranes with an isothiocyanate derivative followed by radioligand binding using [3H]N-methylscopolamine diminished the Bmax value, but did not affect the Kd value. The receptor binding site was not restored upon repeated washing, indicating that irreversible inhibition had occurred. IC50 values for the irreversible inhibition at rat forebrain muscarinic receptors were 0.15 nM and 0.19 nM, for derivatives of pirenzepine and telenzepine, respectively. The isothiocyanate derivative of pirenzepine was non-selective as an irreversible muscarinic inhibitor, and the corresponding derivative prepared from telenzepine was 5-fold selective for forebrain (mainly m1) vs. heart (m2) muscarinic receptors. PMID- 1625526 TI - Influence of amygdala catecholamines on ovarian and adrenal medullary secretion. AB - The amygdaloid complex participates in the modulation of endocrine functions, and contains measurable amounts of noradrenaline (NA) and dopamine (DA). This study examined the contribution of the amygdaloid catecholaminergic systems to the regulation of the adrenal medulla and the ovary. To accomplish this the neurotoxin 6-hydroxydopamine (6-OHDA) was bilaterally injected into the basolateral nucleus of the amygdala (ABL) in cycling rats. The contents of NA and DA in right and left amygdala decreased significantly in lesioned animals with respect to sham lesioned animals, but hypothalamic levels were not different between groups. Administration of 6-OHDA to rats increased the NA, DA and adrenaline (A) contents of the adrenals compared to vehicle treated rats. In addition, lesioned animals showed a significant increase of NA and DA contents in the ovary, although A levels did not differ between groups. Serum oestradiol (O) concentrations were significantly lower in lesioned animals than in controls. These data suggest that the amygdaloid catecholaminergic systems exert an inhibitory effect on catecholamine content of the adrenals and the ovary, and influence the ovarian oestradiol secretion mechanism. PMID- 1625527 TI - Whole blood serotonin levels in chronic renal failure. AB - Whole blood serotonin levels were investigated in a control group (n = 35) and in a group of chronic renal failure patients (n = 127) on various treatment regimen i.e. conservative treatment (n = 39), maintenance haemodialysis (n = 35) and after renal transplantation (n = 53). The whole blood serotonin levels, as determined by high performance liquid chromatography, were significantly lower in the chronic renal failure patients than in the control group (p = 0.0001). Whole blood serotonin levels were significantly lower in the white subjects than in the black subjects of the study (p = 0.0001). PMID- 1625528 TI - Association of radiolabeled urogastrone binding with regenerating intestinal mucosa and epidermal growth factor/urogastrone producing organs in rat. AB - In the present study, we have tested the hypothesis that the regeneration of intestinal epithelium is regulated by changes in the uptake of radiolabeled recombinant human urogastrone (125I rhUG) in the regenerating mucosa and epidermal growth factor/urogastrone (EGF/URO) producing organs in the rats. Operations were performed on rats to approximate the ileal mucosa to the serosal surface of the cecum. This procedure allows the regeneration of ileal mucosa onto the serosal surface of the cecum. Groups of 5 rats were killed on the 2nd, 4th, 8th and 12th post-operative days. Two hours before autopsy, rats were given 0.5 ml (50 microCi with 30 micrograms protein) of 125I rhUG intravenously and the following tissues were removed: regenerating mucosa, salivary gland, duodenum, liver and kidney. Results indicated that the uptake of 125I rhUG was significantly greater in the salivary gland and duodenum on the 2nd post operative day which gradually tapered with increasing time after surgery. A similar pattern in the uptake of 125I rhUG was also evident in the regenerating mucosa. Further analysis revealed a significant correlation between the uptake of 125I rhUG in the salivary gland and duodenum vs rate of epithelialization and uptake of 125I rhUG in the regenerative mucosa. These results suggested that the endogenous EGF/URO produced in the salivary gland and duodenum may be a factor in the regulation of intestinal regeneration; however, the mechanism responsible for reflex stimulation of EGF/URO production in these organs is not known. PMID- 1625530 TI - Professional courtesy: a bygone era. PMID- 1625529 TI - Trace dosages of the neurotoxins MPTP and MPP+ may affect brain dopamine in vivo. AB - The present study has examined the effects of systemically administered MPTP and MPP+ upon striatal DA and Dopac of C57 mice, also treated concurrently with either saline or reserpine. MPTP followed by saline did not affect DA level but decreased that of Dopac only at 5.0 mg/kg and higher dosages. The potency of MPTP affecting DA increased greatly when the neurotoxicant was followed by either 5.0 or 10.0 mg/kg reserpine; MPTP at 0.10 mg/kg and higher dosages significantly reversed the DA depleting effects of reserpine. MPP+ (1.0 or 10.0 mg/kg) with saline did not affect either DA or Dopac. In contrast, MPP+ at 0.10 mg/kg and higher dosages, when followed by 10.0 mg/kg reserpine, dose-dependently enhanced the DA depleting effects of reserpine. In agreement with the earlier results obtained in vitro, the present study indicates that MPTP administration at trace level dosages may lead to an inhibition of MAO in vivo. The effect of systemically given MPP+ on DA, however, appears to be more complex in nature, conceivably comprised of actions at the striatal neurones including the intraneuronal vesicles and, possibly, at the substantia nigra which may affect striatum in turn. That MPP+ may have reached brain areas in these experiments is also indicated by the observation of a significant striatal level of 3H-MPP+ after its systemic administration. In conclusion, irrespective of MPTP and MPP+ action mechanisms, trace levels of these neurotoxicants appear to affect brain dopamine neurons. PMID- 1625531 TI - Lyme disease in Maryland: 1987-1990. AB - We describe the epidemiology of Lyme disease in Maryland for 1987 to 1990 when the number of cases reported grew from 23 to 448 and the number of cases meeting the CDC case definition grew from 23 to 238, as well as discuss the implications of increased reporting and diagnosis of Lyme disease. PMID- 1625532 TI - The clinical use of histamine-2 receptor antagonists. AB - Histamine-2 receptor antagonists have been available for fifteen years for the treatment of peptic ulcer disease and related disorders. While very safe, clinicians need to know correct dosing guidelines, drug interactions, and side effect profiles. Long-term therapy should be reserved for patients at high risk of recurrence. PMID- 1625533 TI - Normal sexual development of children: physician roles in bridging gaps in parent child communication. AB - Physicians have opportunities to help a child have pride about his or her body, support the child's sexual self, and encourage shame-free limit setting. By supporting a parental coalition that is resilient and indivisible, physicians help children value their gender role, and may influence the outcome of sexual orientation. PMID- 1625534 TI - Journey of the Maryland International Health Task Force to post-war Kuwait: May 19-27, 1991. AB - Thirty-eight physicians, nurses, hospital administrators, and support personnel- members of the Maryland Medical Task Force--journeyed to Kuwait in May 1991. The experience sensitized members of the Maryland delegation to the specific needs of post-war Kuwait in rebuilding its health care system. PMID- 1625535 TI - James McHenry, M.D. of Fort McHenry in Baltimore Towne. AB - James McHenry, M.D., whose name is best known for the fort immortalized in the Star Spangled Banner, was one of the early members of Med Chi. In addition, he was secretary to George Washington; aide to Lafayette; member of the Maryland Senate, the General Assembly of Maryland, and the US Congress; and signer of the Constitution. PMID- 1625536 TI - Ethical dilemma: a patient refuses a life-saving cesarean. PMID- 1625537 TI - The illiterate client: strategies in patient teaching. PMID- 1625538 TI - Indications, management, and patient education: anticoagulation therapy during pregnancy. AB - Anticoagulation is necessary in a variety of cardiovascular diseases to prevent thromboembolic complications. On a chronic basis, this type of therapy carries with it frustrations and challenges to both the woman and the health care provider related to monitoring, safety, and compliance. These problems are compounded during pregnancy by specific pharmacological considerations that often require substitution of a parenteral agent. Although at first this may seem an additional burden, the clinician can recruit the mother's naturally heightened awareness of health issues, as these extend beyond herself to the well-being of her child, to achieve therapeutic success. PMID- 1625539 TI - Reaching out to mothers with mental retardation. PMID- 1625540 TI - The unheard voices of women: spiritual interventions in maternal-child health. PMID- 1625542 TI - Reviews of research literature: meta-analysis for synthesizing. PMID- 1625541 TI - Issue update: parental notification. PMID- 1625543 TI - Aspirin for prevention of pregnancy-induced hypertension. PMID- 1625544 TI - Physical activity and cardiovascular health. 1st National Meeting of the National Heart, Lung, and Blood Institute. Chevy Chase, Maryland, August 28-28, 1991. PMID- 1625545 TI - Overview of the National Heart, Lung, and Blood Institute Workshop on physical activity and cardiovascular health. PMID- 1625546 TI - The public health burden of a sedentary lifestyle. PMID- 1625547 TI - Cardiovascular benefits and assessment of physical activity and physical fitness in adults. PMID- 1625548 TI - Determinants of physical activity and interventions in adults. PMID- 1625549 TI - Assessment, prevalence, and cardiovascular benefits of physical activity and fitness in youth. PMID- 1625550 TI - Determinants of physical activity and interventions in youth. PMID- 1625551 TI - Acute response and chronic adaptation to exercise in women. PMID- 1625552 TI - Exercise and atherosclerotic heart disease in women. PMID- 1625553 TI - The reproductive system and exercise in women. PMID- 1625554 TI - Exercise in pregnancy. PMID- 1625555 TI - Osteoporosis and exercise in women. PMID- 1625556 TI - Comparison of in vivo and in vitro Hahn T2 measurements in rat lung. AB - We compared in vivo and in vitro Hahn echo T2 measurements in rat lungs in both imaging and nonimaging modes. All measurements could be characterized by multiexponential functions consisting of either two or three exponentials. Essentially the same values of the time constants were observed for spontaneously breathing rats and for excised lungs. PMID- 1625557 TI - 31P magnetization transfer studies in the monkey brain. AB - The forward and reverse rates through the creatine-kinase (CK) catalyzed reaction, phosphocreatine + ADP+ H+ kf in equilibrium with kr creatine + ATP in the in vivo monkey brain were measured using the techniques of saturation transfer (ST) and inversion transfer (IT) 31P nuclear magnetic resonance (NMR) spectroscopy. Independent checks on the ST apparent longitudinal relaxation (tau) data could be obtained from the parameters determined from the IT analyses. At near-equilibrium it is assumed that the forward-to-reverse flux ratio lies close to 1.0. In the monkey brain the value for the forward-to-reverse flux ratio obtained is 1.37 +/- 0.26 calculated from ST with average tau values from IT initial slopes, a value which is not significantly different from unity. The present NMR data point to the CK reaction in the living monkey brain being maintained at or near equilibrium. PMID- 1625558 TI - Modification of the Carr-Purcell sequence for single-shot echo-planar imaging. AB - An artifact caused by the RF field inhomogeneity in echo-planar imaging (EPI) with the CPMG sequence is analyzed. A modified sequence is presented, using 90 degrees phase alternation of the pi pulses, which suppresses the spurious components of the signal. Thus the phase cycling procedure can be avoided and the pi-pulsed EPI experiment can be reduced to a single shot. PMID- 1625559 TI - Magnetization transfer contrast in fat-suppressed steady-state three-dimensional MR images. AB - We demonstrate that magnetization transfer contrast can be used to improve the diagnostic utility of fat-suppressed steady-state three-dimensional gradient recalled images. Fat suppression is achieved using a "jump-return" pair of contiguous shaped pulses. No time interval exists between the pulses, and no RF echo is generated. The sequence normally produces images with "density" weighting. Preparation of the spin magnetization with off-resonance frequency selective excitation creates magnetization transfer contrast which attenuates signal intensity in proportion to the exchange rate of magnetization from free water with magnetization from water bound to macromolecules or protons that have restricted mobility. The resulting images have excellent fat suppression with low sensitivity to motion since no subtraction is used. In addition, the mechanism of signal attenuation is independent of paramagnetic effects, and addition of Gd DTPA produces signal enhancement from vascularized regions of tissue. Examples are presented for the knee and breast, where the observation of pathology with signal enhancement from Gd-DTPA is improved over conventional 3D fat-suppressed images. PMID- 1625560 TI - Factors influencing the accuracy and precision of velocity-encoded phase imaging. AB - Velocity-encoded phase contrast imaging is being used increasingly in clinical imaging for quantization of blood flow. In this study, the accuracy and precision of ascending aorta flow measurements were found to depend on several subtle aspects of the scan prescription and image analysis. While the usual scan parameters such as TR, TE, and flip angle gave incremental changes in the flow measurements, four additional factors that had a much greater effect on the measurements were identified. These factors were (1) the zero velocity (background) pixel value, (2) the size and shape of the vessel region of interest, (3) the maximum velocity encoded in diastole, and (4) the temporal resolution. Statistical analysis was done on a total of 48 scans on nine normal subjects to confirm the significance of the measured differences using the various choices for each of these factors. These factors must be considered if accurate and precise measurements of blood flow are desired. Estimates of accuracy and precision suggest that quantitative flow measurements from velocity encoded MR imaging can be clinically useful. PMID- 1625561 TI - Analysis of hybrid imaging techniques. AB - Hybrid imaging techniques have been proposed as a means of decreasing imaging time without the cost and technical constraints of echo planar imaging. With this technique phase encoding measurements acquired at different echo times in more than one multiecho experiment are used to form a single image. This study analyzes the trade-offs which occur in the selection of this technique over more conventional imaging in terms of signal/noise, contrast, resolution, imaging time, and efficiency. Hybrid imaging is shown to be advantageous when raw speed is essential such as in abdominal or pediatric imaging. When coverage rather than time becomes the important factor, hybrid imaging does not offer a significant advantage over conventional methods. T2 decay will also serve as a roll-off filter which will reduce the spatial resolution, but not the noise, for short TE hybrid imaging. PMID- 1625562 TI - Theory of contrast agents in magnetic resonance imaging: coupling of spin relaxation and transport. AB - The role of diffusive transport on the enhancement of nuclear spin relaxation through NMR contrast agents is described by means of diffusion-Bloch equations. These equations are solved in the mean relaxation time approximation [W. Nadler and K. Schulten, J. Chem. Phys. 82, 151-160 (1985)]. A model presented considers relaxation enhancement in tissue in which contrast agents confined to intravascular spaces affect nuclear spin in the extravascular volume. We show how the mean relaxation time depends on capillary density, on permeability, and on diffusion. A second model describes enhanced phase relaxation of liver tissue in the presence of magnetic particles in Kupffer cells. The relationship between relaxation rate and density of Kupffer cells is investigated. The diagnostic value of enhanced nuclear relaxation in the presence of contrast agents is discussed on the basis of the systematic mathematical results obtained. PMID- 1625563 TI - MR imaging of anisotropic and restricted diffusion by simultaneous use of spin and stimulated echoes. AB - A new magnetic resonance imaging technique for evaluating anisotropic and restricted diffusion effects in a single experiment is described. The method is based on a pulse sequence that simultaneously excites a spin echo (SE) and a stimulated echo (STE) and contains two pairs of diffusion-sensitive gradient pulses. The diffusion attenuation of the SE and STE can be controlled independently by separate adjustment of the parameters associated with each pair of the diffusion-sensitive gradient pulses. This method can be more time efficient than acquiring separate SE and STE images for the same study. Furthermore, the pulse sequence minimizes the effect of motion and instrumental and physiological variations that occur between separate image acquisitions which can give rise to artifactual results when difference imaging is employed. In addition to applications to anisotropic and restricted diffusion, this technique can be used for: (1) simultaneous acquisition of T2-weighted and diffusion weighted images during cerebral ischemia studies; (2) calculation of diffusion coefficients from a pair of diffusion-weighted images; (3) separating fast and slow diffusion components in a single imaging experiment; and (4) two-dimensional velocity-encoded imaging. PMID- 1625564 TI - A fast gradient-recalled MRI technique with increased sensitivity to dynamic susceptibility effects. AB - A fast imaging method that is based on gradient-recalled echoes of spins whose excitation and echo formation are separated by more than one TR period is presented. This method does not incorporate chemical-shift refocusing and thus results in drastically increased sensitivity to dynamic susceptibility effects, while maintaining a short total imaging time. The efficiency of the new technique is demonstrated in dynamic contrast-enhanced experiments (bolus tracking) in the cat brain using a duration of 600 ms for each image. Blood volume maps are derived with expected contrast between white and gray matter. PMID- 1625565 TI - Effects of the interaction between ferric iron and L-dopa melanin on T1 and T2 relaxation times determined by magnetic resonance imaging. AB - T1 and T2 relaxation times of agar phantoms containing L-dopa melanin and Fe3+ were measured under MRI conditions. Fe3+ shortened T1 and T2 relaxation times. Melanin influenced relaxation times only in the presence of Fe3+; thus, contrast in MR images of the basal ganglia may depend upon levels of both paramagnetic iron and neuromelanin. PMID- 1625566 TI - Analysis of phospholipids in brain tissue by 31P NMR at different compositions of the solvent system chloroform-methanol-water. AB - Brain phospholipids can be quantitated by high-resolution 31P NMR of crude brain tissue extracts in the solvent system chloroform-methanol-water (+EDTA) which was introduced recently (P. Meneses and T. Glonek, J. Lipid Res. 29, 679 (1988)). Phospholipid resonance positions depend on the type of tissue extract and on solvent composition. The effects of systematic variation of the solvent system on phospholipid NMR profiles are presented. Resolution can be optimized by adjustment of the solvent composition. Virtually all phospholipid classes can be resolved, and the major phospholipids in brain: sphingomyelin and phosphatidyl choline, -serine, -inositol, -ethanolamine, and -ethanolamine plasmalogen can be quantitated easily. Additional resonances have been assigned to phosphatidylcholine plasmalogen, alkylacyl-phosphatidylcholine and phosphatidylinositolbisphosphate. NMR offers a rapid method for quantitative analysis of the phospholipid composition in brain tissue which requires minimum sample handling. PMID- 1625567 TI - 31P NMR of electrically stimulated rectus femoris muscle: an in vivo graded exercise model. AB - This study reports on the development of a model for studying skeletal muscle metabolism in humans using NMR spectroscopy. Graded exercise was simulated using electrical stimulation in 10 healthy, fit subjects (mean VO2max = 53 +/- 4 ml.kg 1.min-1). The effects of varying the stimulation parameters, namely, the stimulation frequency, the stimulation intensity, and the duty cycle, as well as the spectral interrogation volume, were compared using data acquired from the rectus femoris muscle. With stimulation, the inorganic phosphate to phosphocreatine concentration ratio ([P(i)]/[PCr]) and the intracellular pH both follow curvilinear relationships over the stimulation frequencies from 3 to 30 Hz, with the magnitude of the observed change related closely to stimulation intensity and duty cycle. Oxidative phosphorylation predominates at stimulation frequencies below 12 Hz, while anaerobic metabolism increases sharply above 12 Hz. Our findings show clearly the interdependence of the effects of the various stimulation parameters and emphasize the care that must be exercised in interpreting the physiological significance of the biochemical data obtained from electrical stimulation models used to study skeletal muscle metabolism. PMID- 1625568 TI - Single-input double-tuned Foster-type probe circuit. AB - Synthesizing two different values of inductance from a given sample coil for use in a single-input double-tuned circuit is possible by means of three extra LC elements. A detailed analysis with derived equations shows how to calculate the circuit component values and what to expect from this kind of probe. It also derives the upper limit of the trap coil/sample coil inductance ratio beyond which no solution exists to double-tune the 31P-1H probe. The general expression for the channel efficiency shows that the latter is a function not only of the inductance of the coils, but also of their quality factor and of the operating frequencies. A numerical example is given illustrating good agreement between experiment and theory provided high quality rf capacitors are used. PMID- 1625569 TI - Quantitative MR in the diagnosis of multiple sclerosis. AB - In patients with multiple sclerosis (MS), the apparently uninvolved cerebral white matter between demyelinated plaques may have biochemical abnormalities. To what degree the changes in the white matter contribute to symptomatology in MS is unknown. In 39 patients with multiple sclerosis, and in 39 age-matched nondiseased volunteers, T1 and T2 were calculated from spin-echo images in four regions of apparently uninvolved white matter. In three of four white matter areas, the average T1 and T2 were significantly longer in the patients than in the controls. The T1 correlated with the disability, measured by the Kurtzke Extended Disability Status Scale, although the correlation was marginally significant. The results suggest that in patients with MS, white matter disease that is not visualized in MR as distinct foci of abnormal signal intensity may contribute to disease burden and disability. PMID- 1625570 TI - Fast and accurate measurements of T1 using a multi-readout single inversion recovery sequence. AB - TOMROP is a multiple readout single inversion-recovery sequence which may potentially allow the measurement of multi-exponential T1 recoveries in vivo by NMR imaging. It is shown that several important modifications must be made to this sequence to permit T1 to be measured accurately and reliably. With these modifications it is possible to measure T1 with a mean systematic error of -1.5% (-0.3% for samples with T1 greater than 300 ms), a mean accuracy of 3.1% (2.1% for samples with T1 greater than 300 ms) and a mean repeatability of 1.4% (1.4% for samples with T1 greater than 300 ms), using data collected in 6.4 min from sixteen 128 x 128 matrix images. PMID- 1625571 TI - Proton nuclear magnetic resonance lineshape studies on human blood plasma lipids from newborn infants, healthy adults, and adults with tumors. AB - The usefulness of proton NMR spectroscopy of human blood plasma for cancer research has been extensively studied in recent years. Two main starting points have been offered by Fossel et al. (N. Engl. J. Med. 315, 1369 (1986)) and Mountford et al. (FEBS Lett. 203, 164 (1986)). In this work the experimental proton NMR spectra of blood plasma were analyzed with the aid of the multivariate lineshape fitting method. An appropriate model structure, in terms of the various lipoprotein (VLDL, LDL, and HDL) signals, for the methylene region was used. Neonates, healthy adults, and adults with nonmalignant and malignant tumors were studied. The linewidth of the methylene region was found to be linearly dependent on the relative concentrations of the lipoproteins. The correlation coefficient was -0.89 (P less than 0.001) for VLDL and 0.88 (P less than 0.001) for HDL. A correlation between VLDL concentration and age, 0.76 (P less than 0.001), was also established. VLDL was modeled using two components. The half-linewidth of the lower field component was slightly elevated for the adults with large metastases. This might be in association with the fucose-containing proteolipid complex detected earlier in cancer cells or in sera of cancer patients. Some signals of this complex may fall in the same region of the spectra. The spectra for the neonates were indicated to be totally different from the adults. This and other related questions were explained by means of the model parameters and the relative concentrations of the lipoproteins VLDL, LDL, and HDL. The presented technique can be used as a rapid research tool for figuring out the relative concentrations of the lipoproteins in blood plasma and explaining the reasons behind the changes in the spectra. PMID- 1625572 TI - Control of translation initiation in Saccharomyces cerevisiae. AB - The first observations regarding the control of translation initiation in the yeast Saccharomyces cerevisiae were made by Fred Sherman and his colleagues in 1971. Elegant genetic studies of the CYC1 gene resulted in the formulation of 'Sherman's Rules' for translation initiation as follows: (i) AUG is the only initiator codon. (ii) the most proximal AUG from the 5' end of a message will serve as the start site of translation; and (iii) if the upstream AUG codon is mutated then initiation begins at the next available AUG in the message. Hidden within these rules is the mechanism of eukaryotic translation initiation, as these very same rules were later shown to apply to higher eukaryotic organisms and were formulated into the scanning model. However, only in the past five years has yeast been taken seriously as an organism for studying the mechanism of eukaryotic translation initiation. The basis for this is that the yeast genes for at least four mammalian translation initiation factor homologues have been identified and the number is growing. Similar factors suggest similar mechanisms for translation initiation between yeast and mammals. For some translation initiation factors, the genetics of yeast has provided new insights into their function. A mechanism for regulating translation initiation in mammalian cells is now evident in yeast. It seems clear that the molecular genetics of yeast coupled with the available in vitro translation system will provide a wealth of information in the future regarding translational control and regulatory mechanisms. The purpose of this review is to summarize what is known about translational control in S. cerevisiae. PMID- 1625573 TI - Genomic diversity and organization of virulence genes in the pathogenic anaerobe Clostridium perfringens. AB - Pulsed-field gel electrophoresis has been used to assess genomic diversity and to identify virulence regions in 10 strains, representing all five serotypes, of the anaerobic pathogen Clostridium perfringens. Detailed physical and gene maps of the approximately 3.6 Mb circular chromosomes have been established in eight cases and used to deduce a consensus map. With one exception the chromosomal arrangement was relatively constant and map comparison allowed three hypervariable regions to be identified. One of these was associated with the enterotoxin gene, cpe, which is an important cause of human diarrhoea following the ingestion of food contaminated with C. perfringens. Another variable region spanning the major virulence gene plc, which encodes the cytolytic toxin, alpha, was located near oriC in all cases whereas the gene for another lethal typing toxin, epsilon, was borne by an episome. It now seems likely that the serological variations, and the changes in the pathogenic spectrum which constitute the C. perfringens typing system, may be due entirely to the loss, or acquisition, of extrachromosomal genetic elements. PMID- 1625574 TI - IRE1 encodes a putative protein kinase containing a membrane-spanning domain and is required for inositol phototrophy in Saccharomyces cerevisiae. AB - A novel gene, IRE1, of Saccharomyces cerevisiae was cloned through genetic complementation of a myoinositol auxotrophic mutant. The predicted amino acid sequence indicated that IRE1 encodes a protein of 126983 Da with two highly hydrophobic regions, probably a signal sequence and a membrane-spanning region. The carboxy-terminal region of IRE1 showed close sequence similarity to the catalytic domains of protein kinases. Disruption of the IRE1 locus caused myo inositol auxotrophy. The IRE1 product is very likely a protein kinase required for myo-inositol synthesis. PMID- 1625575 TI - Molecular genetic analysis of the Rhizobium meliloti fixK promoter: identification of sequences involved in positive and negative regulation. AB - Transcription of the Rhizobium meliloti fixK gene is induced in symbiotic and microaerobic growth conditions by the FixL/FixJ modulator/effector pair. Transcription of fixK is also negatively autoregulated. By 5' deletion analysis, the involvement in negative regulation of a DNA region between -514 and -450 with respect to the transcription start was demonstrated. Site-directed mutagenesis allowed us to show that a sequence homologous to the binding site of the Escherichia coli Fnr protein, centred at position -487, participates in this effect. However, deletion or mutagenesis of this Fnr-like sequence does not completely eliminate FixK-dependent repression, which suggests that either an additional DNA region is involved in negative regulation or that it is mediated at the level of fixLJ transcription. Deletion analysis also allowed the definition of a DNA region involved in FixJ-mediated activation of the fixK promoter, between -79 and -42. Different point mutations in the -60, -45 and -35 regions were shown to affect promoter activity. In some cases, the activity of mutant promoters could be partly or fully restored by increasing the expression of the fixLJ regulatory genes, in an E. coli strain harbouring a plasmid with fixLJ under the control of an inducible (p-tac) promoter. PMID- 1625576 TI - Carbon catabolite repression can account for the temporal pattern of expression of a penicillin biosynthetic gene in Aspergillus nidulans. AB - Aspergillus nidulans synthesizes penicillins as secondary metabolites when grown under certain culture conditions. Broths containing carbon (C) sources that give rise to carbon catabolite repression (CCR) support a much lower antibiotic yield than broths with non-repressing C sources. Steady-state levels of the isopenicillin N synthetase (IPNS) gene transcript are considerably reduced in mycelia grown with repressing C sources and are depressed in mycelia grown with sugars which do not cause CCR, indicating that penicillin biosynthesis is regulated by CCR through transcriptional control of structural genes. CCR is sufficient to explain the temporal window of expression of the IPNS gene during the growth cycle since (i) the transcript becomes derepressed as soon as the concentration of a repressing C source drops to non-repressing levels and (ii) derepressing C sources sustain derepressed IPNS transcription at all tested moments of the growth cycle. Several tested hypofunctional mutations in creA (the negatively acting regulatory gene which mediates CCR in A. nidulans) do not cause full derepression of IPNS transcript in the presence of a repressing C source. The slight degree of IPNS derepression caused by some creAd (derepressed) alleles parallels the strength of the mutation (as determined by the morphological effect they elicit). PMID- 1625577 TI - Identification of individual amino acids required for secretion within the haemolysin (HlyA) C-terminal targeting region. AB - The release of haemolysin from Escherichia coli involves direct secretion across both the inner and outer membranes. Secretion of HlyA is dependent upon a specific membrane export complex composed of HlyB, -D and possibly TolC. HlyA is targeted to the medium via the membrane translocation complex, by a novel C terminal secretion signal. Previous studies involving deletion and fusion analyses have given contradictory results for the minimal length (20-60 residues) of this HlyA signal region and little is known of the nature of the specific residues and structural features required for function. In this study we have analysed, quantitatively, the effect upon secretion of many point mutations introduced into the HlyA C-terminus. The results indicate the presence of a minimal secretion signal domain whose proximal boundary extends to at least residue -46 and which contains at least four individual residues essential for maximal secretion levels. We propose that such residues act co-operatively, forming multiple contact points with the translocator proteins, with the 'best fit' promoting maximal levels of secretion. PMID- 1625578 TI - Involvement of the Arc system in redox regulation of the Cob operon in Salmonella typhimurium. AB - Transcription of the cobalamin biosynthetic (cob) genes in Salmonella typhimurium is induced during anaerobic growth. Two mutants defective in induction of the Cob operon were isolated. The mutants showed decreased anaerobic induction, both during conditions of fermentation and anaerobic respiration, relative to the wild type. The mutant genes were localized by Hfr and transduction mapping to 100 minutes and 69 minutes on the chromosome. The mutants were sensitive to the dye toluidine blue. The mapping and the dye sensitivity suggest that these mutants are defective in the arcA and arcB genes, not previously identified in Salmonella typhimurium. Thus the regulatory function of the Arc system is expanded to include anaerobic activation of the Cob operon. PMID- 1625579 TI - The spo0A gene is implicated in the maintenance of non-complementing diploids in Bacillus subtilis. AB - Bacillus subtilis can exist in a diploid state in which two genetically distinct chromosomes co-exist in the same cell and yet only one of them is expressed, thereby determining the phenotype. Such cells are called non-complementing diploids (Ncds). In this study, two types of experiments are reported which indicate that a previously known pleiotropic gene, spo0A, plays a role in the maintaining the diploid state, as follows. (i) When protoplasts of two Spo0A mutant strains were fused, the resulting products continued to segregate cells of both parental phenotypes for many more divisions than had been reported previously. (ii) When a stable Ncd (an Ncd in which the unexpressed markers are not spontaneously activated at a detectable level) harbouring a chloramphenicol acetyltransferase gene on the silent chromosome was transformed with spo0A null alleles the transformants often expressed chloramphenicol acetyltransferase activity. Together these results indicate that the spo0A gene is involved in maintenance of the diploid state in both unstable and stable Ncds. PMID- 1625580 TI - Cloning of genes affecting capsule expression in Staphylococcus aureus strain M. AB - Staphylococcus aureus strain M produces large amounts of capsular polysaccharide. It produces a non-encapsulated variant at a frequency of 0.01% at 37 degrees C. At high temperature (43 degrees C), the frequency of capsule loss was shown to be 1-38%. A 19 kb plasmid and a prophage were found to be carried by the M strain, but curing of these elements did not affect capsular production. To clone the capsular (cap) genes, a plasmid library of S. aureus M was constructed directly in S. aureus RN4200. The library was then infected with phage 80 alpha. After transduction of the phage lysates to a Cap- mutant derived from M strain, a recombinant plasmid was obtained which complemented the mutant to a Cap+ phenotype. Chromosomal walking experiments were used to clone additional nearby cap genes. Complementation tests using a collection of Cap- mutants showed that most of the mutants were complemented by a 19.4 kb DNA fragment, suggesting that the majority of the cap genes affecting capsule production are clustered together. PMID- 1625581 TI - Mutational analysis of the operon (hyc) determining hydrogenase 3 formation in Escherichia coli. AB - In-frame deletions were introduced into each of the eight genes of the hyc operon coding for products required for the formation of the formate hydrogenlyase (FHL) system. The deletions were transferred to the chromosome and the resulting mutants were analysed for development of formate dehydrogenase H and hydrogenase 1, 2 and 3 activity. It was found that hycA, the promoter-proximal gene, is a regulatory gene and that it codes for a product counteracting transcriptional activation by FhlA. Deletions within the hycB to hycH genes specifically affected formate dehydrogenase H activity or hydrogenase 3 activity, or both. None of the mutations affected hydrogenase 1 or 2 activity. A model is proposed for the functional interaction of the different hyc operon gene products in the formate hydrogenlyase complex, which is based on the results of the mutational analysis, on the determination of the subcellular localization of the FdhF, HycE, HycF and HycG polypeptides and on the similarity of hyc gene product sequences with those from other hydrogenase systems. HycH, the product of the most promoter-distal gene, does not seem to form part of the functional FHL complex but rather is required for the conversion of a precursor form of the large subunit of hydrogenase 3 into the mature form. PMID- 1625582 TI - AIDA-I, the adhesin involved in diffuse adherence of the diarrhoeagenic Escherichia coli strain 2787 (O126:H27), is synthesized via a precursor molecule. AB - The adherence mechanisms of enteropathogenic Escherichia coli (EPEC) to epithelial cells are still not understood. To study the molecular basis of the diffuse adherence (DA) phenotype exhibited by diarrhoeagenic E. coli expressing classical EPEC serotypes we investigated strain 2787 (O126:H27) isolated from a case of infantile diarrhoea. A 6.0 kb plasmid-derived DNA fragment mediates the DA phenotype and encodes the 100 kDa adhesin protein AIDA-I (adhesin involved in diffuse adherence). Sequencing of the entire fragment revealed two open reading frames which encoded proteins of 45 kDa and 132 kDa, respectively. The 132 kDa protein has been identified as an AIDA-I precursor protein. After cleavage of the signal sequence further processing at the C-terminus of the 132 kDa precursor leads to the mature approximately 100 kDa AIDA-I. While the exact function of the cytoplasmic 45 kDa protein is not known, preliminary evidence indicates that it is necessary for the correct maturation of AIDA-I. The AIDA-I precursor exhibits significant homology with the virG(icsA) protein of Shigella flexneri which seems to be involved in the intercellular spread of invasive Shigella organisms. PMID- 1625583 TI - nov: a new genetic locus that affects the response of Escherichia coli K-12 to novobiocin. AB - We have identified a new gene locus (nov) affecting the resistance of Escherichia coli K-12 to novobiocin. The gene also affects, although to a lesser extent, tolerance to another gyrase inhibitor coumermycin. Transductional and complementation analysis show that nov is located between att phi 80 and the osmZ (hns) genes at minute 27 of the E. coli K-12 genetic map. In standard laboratory strains of E. coli K-12 nov exists at least in two allelic forms. PMID- 1625584 TI - Insertional mutagenesis in the extreme thermophilic eubacteria Thermus thermophilus HB8. AB - The transcription and translation signals of the S-layer gene (slpA) from Thermus thermophilus HB8 have been used to express a thermostable kanamycin adenyl transferase gene in this organism. The chimaeric resistance gene was inserted in vitro into slpA to produce different inactive forms of the gene, which were used to transform T. thermophilus HB8. After 48 hours of incubation at 70 degrees C, only two constructions that contained the kat gene flanked by Thermus sequences from both sides of slpA were able to produce protein layer (P100)-defective mutants. The mutants obtained with both constructions showed identical protein patterns, in which a major 50 kDa protein and two other minor proteins were tentatively identified as P100 fragments, expressed from the extreme 5' end of slpA. They also exhibited important phenotypic defects, such as slow growth in liquid broth, a tendency to aggregate as 'rotund bodies', a twisted filamentous shape, and an extreme sensitivity to lysozyme, suggesting protective and shaping roles for the S-layer in T. thermophilus HB8. These results also demonstrate for the first time the feasibility of using selective antibiotic-resistance markers in extreme thermophiles. PMID- 1625585 TI - The VirF protein from Shigella flexneri is a member of the AraC transcription factor superfamily and is highly homologous to Rns, a positive regulator of virulence genes in enterotoxigenic Escherichia coli. PMID- 1625586 TI - The provision of the maternity services in the UK. PMID- 1625587 TI - An evaluation of the importance of formal, maternal fetal movement counting as a measure of fetal well-being. AB - Maternal perception of fetal movements has, over the years, become recognised as a valuable tool for early detection of fetal compromise. Several studies published in the mid-1970s have demonstrated that a reduction or cessation in maternally perceived fetal movements may precede antepartum late fetal death by a day or longer. From these findings formal fetal movement counting emerged as a valuable, non-invasive method of assessing fetal well-being; the belief being that clinical actions taken on the basis of reduced fetal movement counting may prevent antepartum death or morbidity. Conversely, more recent studies have failed to demonstrate that there is a beneficial effect of a formal, fetal movement counting policy on antepartum death. It is not disputed that fetal movements are of clinical importance but it seems that routine daily counting of fetal movements by women followed by appropriate action when movements are reduced offers no advantages over formal inquiry about fetal movements during standard antenatal care. Thus, the application of formal, maternal fetal movement counting as a method of fetal surveillance to reduce late antepartum death must be questioned. PMID- 1625588 TI - The role of the midwife and consumer groups as advocates for the rights of the consumer. AB - There has been an increasing number of consumer advocacy groups actively lobbying for the right of women to have an informed choice about care and facilities for their childbearing. Mothers and Midwives Action (MAMA) South Australia Inc was formed in 1989 to campaign for improved childbirth services for the women of South Australia. Although the group has been involved in a number of issues this article will concentrate on two, the group's participation in the planning of a Birthing Unit at the new Adelaide Medical Centre for Women and Children and the setting up of a Childbirth Information Centre. The difficulties and complexities of successful lobbying will be discussed within the context of the Ottawa Charter. Midwives in their advocacy role need to be more aware of consumer issues. They must be prepared to participate actively, supporting the consumer when appropriate, both on a personal level and collectively as a professional group. The MAMA group in Adelaide SA has been both supportive and helpful in the production of this article. PMID- 1625589 TI - An evaluation of pre-registration midwifery education in England. Research design: a case study approach. AB - In this paper some aspects of research design are described and discussed. A national study to evaluate pre-registration midwifery education in England is currently in progress. As part of that study six case study sites have been selected. How those sites were selected and the theory and method of the case study approach are discussed in this paper. The value of the case study approach is discussed as are methodological issues of the case study method. What is a case? Are case studies representative? How can you generalise from case studies? What is theoretical sampling? What is the difference between statistical and logical inference? These are some of the questions raised and examined. It is suggested that an understanding of these theoretical issues and the research process is important to understand the research findings. By making the research design explicit and describing the research process the study also adopts a reflexive approach. PMID- 1625590 TI - A reconsideration of the factors affecting birth outcome in Pakistani Muslim families in Britain. AB - Over recent years, Bradford has had a consistently high perinatal mortality rate (PNMR), especially amongst its Asian population, 66% of whom originate from Pakistan. There is a high incidence of consanguineous marriages reported among Pakistani and Muslim couples. Often, this observation is used to explain their higher PNMR and congenital malformation rates. The factors affecting birth outcome in Pakistani women are complex and interrelated. Socioeconomic, genetic, biological and environmental factors all contribute to adverse birth outcome. In addition, these are complicated by discrimination, communication barriers and culture blaming. The aim of this paper is to challenge midwives and other health professionals to reconsider the overwhelming emphasis placed on consanguinity as a factor affecting birth outcome, and to recognise the impact and interplay of other confounding variables. PMID- 1625591 TI - Temperature changes during the first day of life in the North Staffordshire Maternity Hospital. AB - A prospective study of post-delivery temperature changes from birth to 24 h, carried out in a busy District General Hospital is reported. The temperature fall after delivery was less than expected and reflected a high level of awareness of the dangers of hypothermia. On the basis of the findings of the survey, hypothermia in the first 24 h can be defined as a rectal temperature of less than 36.4 degrees C. Those babies who did become hypothermic were significantly more likely to be of low birth weight or preterm gestation. PMID- 1625593 TI - Case in point: contract protects employee from capricious discipline. PMID- 1625592 TI - Aging population requires increased education in gerontological nursing. PMID- 1625594 TI - The origin and the progression of varicose veins. AB - It is proposed that pathological varicosities begin as acute dilator responses of normal veins to noradrenaline released from the vasa vasorum of the vein; the noradrenaline is part of a circulating pool formed by overflow following adrenergic nerve activity. In health, a minimal quantity of noradrenaline routinely flows by reflux to the vasa where it has a negative feedback, venodilator effect. However, when the volume of reflux becomes excessive, the noradrenaline in it abolishes venoconstrictor tone, thereby creating a varicosity. Excessive venous reflux over a short period causes no significant hypoxic damage to the vein wall or any other tissues and any damage associated with it regresses when the excess reflux ceases. However, if excessive reflux is persistent then a time comes when irreversible hypoxic structural changes occur in the vein wall and in other tissues affected by the reflux. The structural pathology associated with varicose veins reflects the effect of the long-term tissue hypoxia associated with that condition. PMID- 1625595 TI - Manifestations of pediatric AIDS: proposed mechanisms of transmission. AB - Pediatric Acquired Immunodeficiency Syndrome (AIDS) is expected to increase by greater than 75% by 1993. Most of these infants will become infected with the Human Immunodeficiency Virus (HIV) through the mother. It is unclear exactly how the virus is passed from mother to child. The nature of HIV infection is described in this paper, and several mechanisms relevant to its transfer are proposed. PMID- 1625596 TI - Purinergic stimulation of cell division and differentiation: mechanisms and pharmacological implications. AB - Extracellular purine nucleosides and nucleotides in micromolar concentrations stimulate proliferation of a variety of cell types in vitro and in vivo. As well they act synergistically with NGF to stimulate neurite outgrowth from PC12 cells. A variety of purine nucleosides and deoxyribonucleosides promote cell proliferation and increase intracellular cAMP. Their activities are inhibited by adenosine A2 receptor antagonists. Only adenosine interacts with the A2 receptor. We propose that the other nucleosides and deoxyribonucleosides inhibit extracellular adenosine deaminase, thereby increasing the extracellular concentration of adenosine. The nucleotides apparently act by stimulating P2y receptors coupled to inositol phosphate metabolism. We propose that the nucleosides and nucleotides act synergistically with other growth factors because each has distinct but complementary second messenger systems. If our hypotheses are correct, it should prove possible to modulate the growth and morphogenesis in several cell types using drugs that inhibit or stimulate adenosine A2 or purine P2y receptor agonists or the second messenger systems coupled to these receptors. PMID- 1625597 TI - Membrane fluidity, reactive oxygen species, and cell-mediated immunity: implications in nutrition and disease. AB - Membrane-associated functions are profoundly influenced by the fluidity and physical state of the membrane. These two features are in turn determined by the membrane lipid acyl chain profile. Reactive oxygen species (ROS) modify the acyl chains by lipid peroxidation of the unsaturated chains, thus affecting the fluidity and physical state of the membrane. By enhancing endogenous ROS levels, therefore, aging, and disease affect integral membrane function, such as the cell mediated immune (CMI) reaction involving phagocyte membrane NADPH oxidase. This enzyme relies on triggering by membrane-inserted protein kinase C (PKC), for its superoxide (O2-) producing function. The molecular mechanism of the depressed immunocompetence in the aged, and in disease and malnutrition, may reside in the down-regulation of these two enzymes by excess ROS. These excess ROS arise from activated phagocytes in disease states, and from enhanced ROS from other sources in the aged, as well as from the decrease in antioxidants in the aged. Research should be intensified on PKC and NADPH oxidase function with the aim of unravelling the molecular mechanism of the depressed immunocompetence, and thence, of formulating appropriate intervention strategies against it. PMID- 1625598 TI - Some thoughts about the importance of X-ray exposure histories for patients. AB - The controversy regarding the importance of the definition and standardization of a radiation exposure history is identified. Cancer incidence is increasing partly due to increased diagnostic accuracy but some over utilization of diagnostic X ray exposure has been linked with increased breast, brain, thyroid and skin cancer, leukemia and multiple myeloma incidence. Since there is a lack of standardization of radiation histories and lack of knowledge by some physicians of radiation exposure dosages, this practitioner has compiled a suggested practical reference list of common radiation exposure dosages and indications for a detailed radiation history with current references. PMID- 1625599 TI - Extracellular purine nucleosides stimulate cell division and morphogenesis: pathological and physiological implications. AB - Extracellular purine nucleosides and nucleotides are ubiquitous, phylogenetically ancient, intercellular signals. Purines are released from hypoxic, damaged or dying cells. Purine nucleosides and nucleotides are potent mitogens for several types of cells such as fibroblasts, endothelial cells and neuroglia. They also induce other cell types to differentiate. For example, they act synergistically with nerve growth factor to stimulate neurite outgrowth from a pheochromocytoma cell line (PC12). We propose that after injury to tissues, including the central nervous system, purine nucleosides and nucleotides interact synergistically with other growth factors. They stimulate proliferation and morphological changes in the various cell types involved in the wound healing response. In the central nervous system this response includes glial proliferation, capillary endothelial cell proliferation, and sprouting of nerve axons. Since many actions of extracellular purines are mediated through specific cell surface receptors, this hypothesis has broad pharmacological implications. PMID- 1625600 TI - Margarines and coronary artery disease. AB - In a previous paper we predicted that health effects of dietary fats in humans would require half a century or more to be understood, instead of the decade or so predicted during 1956 by an Editorial in The Lancet. It would seem that our prediction may have been optimistic since it has now been reported that trans unsaturated fatty acids present in high concentrations in margarines promote hypercholesterolemia in humans. Consequently, there has been a call for the reclassification of dietary fats upon the basis of their hypercholesterolemic properties. Using the latter criterion, therefore, many margarine brands would be classified as coronary artery disease risk foods. The primary adverse metabolic action of trans unsaturated fatty acids is the competitive inhibition of delta-6 desaturase, the hepatic enzyme responsible for the initial metabolic desaturation of the essential fatty acids cis linoleic and cis alpha-linolenic acid. In addition to margarines, many other common foods such as deep-fried foods, many convenience foods and bakery products contain relatively high levels of trans fatty acids. Therefore, since it has become virtually impossible to avoid a consistent, daily dietary intake of trans fatty acids, it would appear that a precautionary, preventative supplementation of the diet with supplements containing the direct metabolic products of delta-6-desaturation of the essential fatty acids, would be prudent. Such supplements are readily available. PMID- 1625601 TI - Generalizing the control process for embryonic genes. AB - Embryonic genes are considered as a separate subset of genes with unique chromatin properties. There is a problem of defining the duration of perturbations of embryonic gene activity that has been chemically induced and the normal relatively longer lasting changes that occur during differentiation. This problem may be related to unique properties of the chromatin of embryonic genes. Methylation of DNA is thought to be only one level of control and the superstructure of chromatin involving heterochromatin is of equal importance to embryonic gene expression. Proto-oncogenes are considered to be embryonic type genes whose activities are regulated under the same mechanisms by which other embryonic genes are regulated. Control aspects are discussed in the light of i) repressor-derepressor and blocking-deblocking mechanisms, ii) activator genes, pseudogenes, LINES, SINES, v-type position effects, iii) effects of ethionine, and iv) steroid hormone effects especially with respect to a subset of repeated rRNA genes which are considered to be structured in embryonic type chromatin. PMID- 1625602 TI - Maintenance of embryonic gene activity into the adult state. AB - It is now apparent that certain embryonic gene activities may be maintained before the transition from embryonic to the adult state takes place. The consequence of such a condition could have far reaching results and create a totally new approach to biotechnology by dealing with epigenetic methods and not gene-splicing methods. For example, if a group of c-oncogenes, believed to be of the embryonic type (1) that are responsible for growth factors which regulate embryonic rates of growth, then large increases in growth rates during the adult stage should occur. Two major alterations seem to be required. One is the interference of DNA methylation patterns using such agents as ethionine (interfering with S-adenoysl-1-methionine synthesis) or azacytidine (interfering with DNA methylase activity). Secondly, a change in chromatin configuration (deheterochromatization?) with agents such as n-butyrate or hexamethylenebisacetamide (HMBA). Maintenance methylases would make the altered (hypomethylated) pattern of the perturbed chromatin invariant after the initial perturbation. Enhancer-promoter mechanics are probably pertinent to this process. PMID- 1625603 TI - The role of catecholamines in gram-negative sepsis. AB - Recently obtained in vitro evidence has demonstrated that neurochemicals such as the catecholamines can dramatically increase the growth of Gram-negative bacteria. Depending on the catecholamine, an up to 100,000-fold increase in the in vitro growth rate of pathogenic Gram-negative bacteria such as Escherichia coli and Yersinia enterocolitica can be observed. Dramatic elevations in the levels of plasma catecholamines have been amply demonstrated to occur as part of the neurophysiological response to infection. It is proposed that the ability of pathogenic bacteria to utilize the host's neurophysiological response to infection to modulate its own growth may govern the eventual clinical outcome of the infection. PMID- 1625604 TI - The properties of the nervous system and the two-growth-types (egg-sperm) concept of carcinogenesis. AB - Some common morphological and functional features of the sperm and of the neuroblast (above all the resistance of the egg once fertilized to penetration of further sperms and of the embryonic cell once innervated to additional innervation) point to their developmental relationship, viz. to continued existence of the sperm, following temporary disappearance and genetic interaction within the egg, in the form of a neuroblast. The egg and the sperm would thus give origin to the two basic growth types of the vertebrate body, viz. the cellular-divisional (of the non-nervous tissues) related to the egg and the neural-extensive originating in the sperm and characterized by sprouting of processes even several decimeters long from a single nerve cell body. The nervous system, in addition to its intricate functions, represents an extremely dense feltwork of nervous trunks, branches and fibres, the 'nervous skeleton' (6), the product of the extensive neural growth which is 'stuffed' with the products of the cellular divisional proliferation of the other, non-nervous tissues. The absence of nerves (or of normal nerves) within the malignant tumours points to cellular 'escape' from the limiting confines of the nervous skeleton as the biological cause of malignancy: the 'escaped' cells pursue the one-growth type way of life instead of the normal two-growth-types way, viz. they revert back towards the egg-condition and acquire embryonic features. Introduction of neuroblasts into the malignant tumour aimed at re-establishment of its nervous skeleton should convert the malignant lesion into a benign one. PMID- 1625606 TI - Cancer epidemiology in Australia: priorities for the 1990s and beyond. PMID- 1625605 TI - The DDT method: an alternative to the use of radiolabelled microspheres for the determination of regional blood flows in the rat. AB - Intravenous administration of the 14C-radiolabelled insecticide DDT--1,1,1 trichloro-2,2-bis-(p-chlorophenyl)ethane--can be used for the estimation of regional blood flows in small rodents. A mathematical model is presented which enables the conversion of relative into absolute blood flows. PMID- 1625608 TI - Health expenditure in Australia. The current dilemma. PMID- 1625607 TI - Caring for carers--a national problem. PMID- 1625609 TI - Genetics and the risk of coronary heart disease. PMID- 1625610 TI - Rabies case in New South Wales, 1990: public health aspects. AB - OBJECTIVES: To identify the source of rabies in the recent case in New South Wales, and to determine the need for post-exposure rabies prophylaxis among contacts of the patient. DESIGN: Information was obtained by face-to-face interview of the dead girl's family and face-to-face and telephone interviews using a questionnaire of health care workers. Other information was gathered from overseas and local sources through telephone and facsimile contact. RESULTS: The girl had migrated from Vietnam in 1984 to Hong Kong, and from there in 1986 to Australia. No evidence of contact with a rabid animal in Australia or Hong Kong was found. There had also been no organ donations from the girl. Four health care workers were given post-exposure rabies prophylaxis. CONCLUSIONS: Because of the lack of evidence of animal contact in Australia and the fact that extremely long incubation periods for rabies have been documented, it was considered that the most likely source of the rabies virus was North Vietnam. Genetic studies of the virus also supported a South-East Asian source. Nevertheless the presumed incubation period--at least six years and four months--is one of the longest recorded. PMID- 1625611 TI - Detection of reversible platelet aggregates in the blood of smokers and ex smokers with peripheral vascular disease. AB - OBJECTIVE: To demonstrate that smoking increases platelet aggregation in vivo, that smoking cessation reverses platelet aggregation and that this explains, in part, why smoking perpetuates the development of peripheral vascular disease. DESIGN: Prospective case-control study involving three groups of patients: smokers with peripheral vascular disease, ex-smokers with peripheral vascular disease and smokers with peripheral vascular disease who quit smoking during the study. SETTING/PARTICIPANTS: Fourteen smokers and seven ex-smokers, new patients with confirmed peripheral vascular disease, attending the vascular clinic at Fremantle Hospital between February and November, 1988. INTERVENTIONS: Blood samples taken weekly from all subjects for five weeks. Week 1 was taken as the baseline before smoking cessation in the six smokers who were assigned to stop smoking during the study. MAIN OUTCOME CRITERIA: Platelet aggregate ratio, an indicator of in-vivo platelet aggregability where an increase in platelet aggregate ratio suggests a decrease in platelet function. RESULTS: Only three of six smokers stopped smoking for the duration of the study. Median platelet aggregate ratios were: smokers = 0.85 (range, 0.79-0.92) v. non-smokers = 0.93 (range, 0.91-1.00). The difference was statistically significant P less than 0.0002. The difference in platelet aggregate ratios between smokers and quitters was not statistically significant. CONCLUSIONS: This study demonstrated an increase in platelet aggregability in smokers compared to ex-smokers but there was no clear evidence that platelet function was fully reversed after only four weeks cessation of smoking. The data suggested that platelet function of the ex smokers had fully reversed to normal over a longer period. This could explain the decreased incidence of complications of peripheral vascular disease in ex smokers. The small number of patients able to quit smoking impeded this study. PMID- 1625612 TI - Aluminium beverage cans as a dietary source of aluminium. AB - OBJECTIVE: To examine the possibility that aluminium beverage cans contribute to the dietary level of aluminium. METHOD: The aluminium content of a variety of beverages from aluminium cans and glass containers was measured. RESULTS: The contents of 106 aluminium cans and bottles representing 52 different beverages all had a higher aluminium content than Newcastle tap water at 1.4 mumol/L, ranging as high as 385 mumol/L. Non-cola soft drinks averaged 33.4 mumol/L from cans and 5.6 mumol/L from bottles. Cola drinks averaged 24.4 mumol/L from cans and 8.9 mumol/L from bottles, whereas beer in cans or bottles averaged about 6 mumol/L. CONCLUSIONS: In general, the aluminium content of beverages from aluminium cans was higher than that from glass containers, and it rose with decreasing pH. Within a given category there was a wide variation in aluminium content. If the speculative link between aluminium intake and Alzheimer's disease is established then beverages from aluminium cans, particularly soft drinks, may be a risk factor. PMID- 1625613 TI - Sexual activity and condom use in high school students. AB - OBJECTIVE: To determine the level of sexual experience and condom use among Year 9 high school students. DESIGN: Self-administered questionnaire to all Year 9 students attending a personal development workshop. SETTING: The study was carried out in two regional high schools in New South Wales, one in an urban area and the other in a rural area. PARTICIPANTS: A total of 253 students in Year 9 at the two high schools; only two students declined to participate. RESULTS: Seventy one students (28.1%) had had intercourse at least once. There was no statistically significant difference between the percentage of male and female students or rural and urban students who had had intercourse. Thirty students (42.3%) always used condoms, 35.2% used them sometimes and the other sexually active students had never used them. The commonest reasons for non-use were unplanned sex, unavailability or no time. CONCLUSIONS: The unpredictability of teenage sexual activity may mean that condoms are not available at the crucial time. Girls appear to have more difficulty in asking for condoms to be used, but the numbers are two small in this survey to draw definite conclusions. If both pregnancy and sexually transmissible diseases are to be prevented among adolescents, sex education must encourage condom use as the first method of contraception for this group and emphasise the need for consistent availability and use. PMID- 1625614 TI - Mild bleeding disorders. A clinical and laboratory study. AB - OBJECTIVE: To investigate in-vitro haemostasis in subjects with symptoms suggesting a mild bleeding disorder. DESIGN: A prospective study in which an extensive range of in-vitro tests were applied unselectively. SETTING: Patients were referred from community-based practices and hospital outpatient services. PATIENTS: Ninety-three consecutive patients were examined. Hospital patients with severe illness were excluded. CLINICAL FEATURES: Patients presented with easy bruising (68%), epistaxis (12%), excessive operative bleeding (7%), menorrhagia (4%), haematuria (3%), dental bleeding (1%) and bleeding from other sites (5%). In no instance was the bleeding life threatening. OUTCOME MEASURES: Results of laboratory tests for patients presenting with the symptoms of a mild bleeding disorder were compared with the results for a healthy reference group. RESULTS: Abnormal results of in-vitro tests were found in 53% of the subjects. Thirteen per cent had a prolonged bleeding time, of whom the majority had abnormal results of other in-vitro tests. Von Willebrand's disease was diagnosed in 7% of patients, although only half of these had a prolonged bleeding time. CONCLUSIONS: Abnormal results of in-vitro tests were prevalent among subjects with symptoms of mild bleeding disorder. Easy bruising was as powerful a clue as any other bleeding manifestation to the presence of an abnormal in-vitro test result. PMID- 1625615 TI - A memory clinic at a geriatric hospital: rationale, routine and results from the first 100 patients. AB - OBJECTIVE: To describe the operation of a memory clinic with reference to the referral pattern, patient characteristics and psychiatric diagnoses, frequency of reversible dementias and utility of brief cognitive screening tools in the detection of dementia. DESIGN: All patients underwent cognitive screening tests (Mini Mental Status Examination, Abbreviated Mental Test Score, Organic Brain Syndrome Scale of the Brief Assessment Scale) and two activities of daily living instruments. Psychiatric diagnoses were made according to criteria of the Diagnostic and statistical manual, third edition revised, of the American Psychiatric Association (DSM-III-R). SETTING: A large geriatric hospital. SUBJECTS: First 100 patients referred. RESULTS: The mean age of the patients was 75.5 years and 75 were women. Seventy-four met DSM-III-R criteria for dementia and a further 13 had other organic brain syndromes. No case of reversible dementia which recovered was encountered. The cognitive screening tools had a high correlation (r = 0.85-0.89) with one another but a much lower correlation with the activities of daily living instruments (r = 0.27-0.37). CONCLUSION: Reversible dementias are unlikely to be detected in a memory clinic at a geriatric hospital, but the assessment process may have other benefits which will need to be assessed in prospective research. The clinic population represents a unique resource for further research on dementia. PMID- 1625616 TI - Plant hair dermatitis. AB - OBJECTIVE: To survey the ill effects of plant hairs on humans in Australia, incorporating new records. DESIGN: Retrospective analysis of new records, in some cases confirmed and supplemented by experimental skin contacts, along with a general survey of relevant literature. METHODS: Reports of accidental injuries submitted to the authors, through either medical or other sources, and to the Botanic Gardens of Adelaide and State Herbarium of South Australia, were studied and compared with existing literature; in some cases the effects were confirmed experimentally. RESULTS: A general survey of plant hair dermatitis in Australia is offered. Most species included have been referred to in the scattered earlier literature, but a few plants not previously recorded as irritating are included, notably Apalochlamys spectabilis, Wisteria sinensis and Grevillea species. Attention is also called to the penetrating and irritating pod spines of Brachychiton spp. (kurrajongs and relatives) and Lagunaria patersonii (Norfolk Island hibiscus or pyramid tree), which are often planted as ornamental street trees. Generally those most likely to receive these injuries are gardeners and children. PMID- 1625617 TI - Hepatitis B virus markers in children and staff in Northern Territory schools. AB - OBJECTIVE: To measure the prevalence of hepatitis B virus (HBV) infection in children and staff at Northern Territory schools. DESIGN: Children in Years 5-7 in 24 selected primary schools were invited, with parental consent, to provide demographic and ethnic details, and a capillary blood sample for tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B surface antigen (anti-HBs). School staff participated on a similar basis. PARTICIPANTS: 1104 children, comprising 556 from ethnic groups (originating from the United Kingdom, Ireland and northern Europe) previously reported as "low HBV prevalence", 439 Aboriginal Australians, and 109 from "other" ethnic groups (originating from Asia, the Pacific, the Middle East and southern Europe); and 209 school staff, comprising 180 from "low HBV prevalence" ethnic groups, and 29 from Aboriginal and other ethnic groups. RESULTS: Prior HBV infection (i.e. serum positive for HBsAg or anti-HBs) was detected in 28.7% of children (46.9% of 439 Aborigines; 13.7% of the 556 children from the "low prevalence" groups and 32.1% of the 109 from the "other" groups). HBsAg was detected in 8.2% of Aboriginal children, in 0.36% of those from "low prevalence" groups, and in 1.8% of those from the "other" groups. Aboriginal children in rural schools had the highest prevalence of HBV: 5.4% were positive for both HBsAg and anti-HBs, and an additional 9.8% were positive for HBsAg alone. In urban schools, the prevalence was highest in the "other" ethnic groups. For school staff, the prevalence of HBV infection was 12.8% for those from "low prevalence" ethnic groups, and 37.9% for those from all remaining groups (including Aborigines). CONCLUSION: In the Northern Territory the prevalence of past HBV infection is high in children and school staff from ethnic groups previously known to be at higher risk of HBV infection. For students and staff from ethnic backgrounds expected to be at low risk, HBV prevalence is greater than in individuals from similar backgrounds in other parts of Australia. HBV vaccination is now offered to all infants in the Northern Territory. These results also provide a rationale for the more widespread use of HBV vaccine in other situations where significant HBV transmission might occur. PMID- 1625619 TI - Managing sore throat: a literature review. II. Do antibiotics confer benefit? AB - OBJECTIVE: To assess the justification for the use of antibiotics in the management of sore throat in general practice. DATA SOURCES: The literature from 1945 to 1990 was systematically screened to identify studies that addressed the question whether antibiotics reduce non-suppurative and suppurative complications and symptoms of sore throat. The key-words, "pharyngitis" and "tonsillitis" were used to identify trials of antibiotics for the treatment of sore throat. STUDY SELECTION: Studies were included in comparison tables if they involved the trial of one or more antibiotics against a control and there was an outcome in terms of reduction in the incidence of acute rheumatic fever, acute glomerulonephritis, acute otitis media, acute sinusitis, quinsy or any symptoms related to the acute illness. RESULTS: The published literature suggests that antibiotic treatment protects patients with sore throat against acute rheumatic fever and some suppurative complications, but not against acute glomerulonephritis. It does not reduce the symptoms. CONCLUSIONS: In Australia, with the exception of socioeconomically deprived Aboriginal communities, the incidence of acute rheumatic fever is probably not high enough to justify the use of antibiotics for sore throat. Protection against suppurative infection seems to be slight and it is difficult to establish the benefit of antibiotic treatment for reducing the symptoms of sore throat. Until more benefits for antibiotic management of sore throat can be demonstrated, it is recommended that infrequent use be adopted. PMID- 1625618 TI - South Australian hypertension survey. General practitioner experiences with drug treatment. AB - OBJECTIVE: To investigate prescribing habits, educational approaches and perceived needs of general practitioners in the drug treatment of hypertension. DESIGN, SETTING AND PARTICIPANTS: Of 156 randomly selected South Australian general practitioners 132 responded to a questionnaire survey. MAIN FINDINGS: Diuretics are the most commonly chosen drug for the initial management of uncomplicated moderate hypertension. Equivalent patients aged 45, 60 and 75 years would be prescribed a diuretic as drug of first choice in 41%, 55% and 68% of cases respectively. Despite this, there are wide differences in the choice of initial therapy between individual practitioners. These differences can have a substantial cost impact, given that in Australia the cost of diuretic therapy for one month can be as low as $1.97 compared with $34.08 for standard angiotensin converting enzyme inhibitor therapy for one month. There was also a perceived need, and demand, for patient education materials to assist practitioners in the drug treatment of hypertension. PMID- 1625620 TI - A case of murine typhus in Queensland. AB - OBJECTIVE: To present a case of murine (endemic) typhus, the first to be reported within the last 30 years in Australia. CLINICAL FEATURES: A 17-year-old pregnant woman presented with a viral-like illness and later developed a spotted rash, fever and headache. INVESTIGATION AND OUTCOME: Sera taken on Day 7 and Day 30 of the illness showed seroconversion to Proteus OX19 (Weil-Felix) and to Rickettsia typhi (by immunofluorescence), indicating recent infection with Rickettsia of the typhus group. Her illness was clinically compatible with murine typhus. She responded well to erythromycin and delivered a normal infant at term. CONCLUSION: Infection with Rickettsia typhi (murine typhus) still occurs in Australia. It can be diagnosed by means of specific serological tests for rickettsial disease, which are superior to the non-specific Weil-Felix test. PMID- 1625621 TI - Rabies. A second Australian case, with a long incubation period. AB - OBJECTIVE: The description of a second case of rabies in Australia, stressing the clinical features and that long incubation periods are possible. CLINICAL FEATURES: A 10-year-old Vietnamese girl presented with fever, shoulder pain, subcutaneous emphysema, swallowing difficulty and agitation. After a period of maniacal behaviour all peripheral and central nervous system function was lost. INTERVENTION AND OUTCOME: Despite maximal intensive care, the patient died. The diagnosis of rabies was made at autopsy. CONCLUSIONS: Rabies occurs in Australia and needs to be considered in the differential diagnosis of acute encephalitis and/or the Guillain-Barre syndrome. Incubation periods of more than six years can occur. PMID- 1625622 TI - Subdural haematoma presenting with transient neurological deficits. AB - OBJECTIVE: To stress that transient neurological deficits do not always imply transient cerebral ischaemia, and may be produced by subdural haematoma. CLINICAL FEATURES: An 80-year-old man was seen for intermittent gait disturbance, with normal findings on initial examination. He was then admitted after the onset of a fixed neurological deficit which worsened. Subdural haematoma was diagnosed by computed tomography (CT). An 80-year-old woman was seen after she had experienced left hemisphere transient neurological deficits. A CT scan showed a left-sided subdural haematoma. INTERVENTION AND OUTCOME: Both patients underwent successful surgery with complete resolution of their symptoms and signs. CONCLUSION: Subdural haematoma is relatively common and must be considered in those with unexplained transient neurological deficits. Magnetic resonance imaging or CT are the diagnostic procedures of choice. Antiplatelet or anticoagulant therapy must not be instituted until subdural haematoma is excluded. PMID- 1625623 TI - Doctor versus laboratory notification of gonorrhoea in Western Australia. PMID- 1625624 TI - Native valve endocarditis and vertebral osteomyelitis caused by Staphylococcus epidermidis. PMID- 1625625 TI - Resistance to ciprofloxacin of respiratory pathogens in patients with cystic fibrosis. PMID- 1625626 TI - Pap smear reminder systems. PMID- 1625628 TI - Ciprofloxacin in cat-scratch disease. PMID- 1625627 TI - "Holistic" health workers. PMID- 1625629 TI - Tuberculosis in Australia--a forgotten disease. PMID- 1625630 TI - Tuberculosis in Australia--a forgotten disease. PMID- 1625631 TI - Tuberculosis in Australia--a forgotten disease. PMID- 1625632 TI - Tuberculosis in Australia--a forgotten disease. PMID- 1625633 TI - Does the doctor listen? PMID- 1625634 TI - The battle of the couches and the rats. PMID- 1625635 TI - In search of the pathogenesis of refractory cervicobrachial pain syndrome. PMID- 1625636 TI - In search of the pathogenesis of refractory cervicobrachial pain syndrome. PMID- 1625637 TI - Sodium cromoglycate for ACE inhibitor cough. PMID- 1625638 TI - The "Ulysses syndrome" in pathology. PMID- 1625639 TI - Basal cell naevus syndrome. PMID- 1625640 TI - Enuresis and body worn alarms. PMID- 1625641 TI - Stevens-Johnson syndrome induced by verapamil. PMID- 1625642 TI - Oxygenation and carbon dioxide elimination during cardiopulmonary bypass. PMID- 1625643 TI - Inotropic support of the failing heart. PMID- 1625644 TI - Incidence of postoperative hypoxemia as detected by pulse oximetry. PMID- 1625645 TI - Differential diagnosis of delayed return to consciousness. PMID- 1625646 TI - The effect of propofol and thiopentone on pentylenetetrazol seizure threshold in the rat. AB - The protective effects of subanesthetic and anesthetic doses of propofol and thiopentone against pentylenetetrazol (PTZ)- induced seizures were studied in the rat. Intraperitoneal administration of propofol and thiopentone at doses producing comparable levels of sedation prior to intravenous infusion of PTZ, resulted in a marker and significant increase in PTZ seizure threshold. However, at all doses, the effects of propofol on PTZ convulsive threshold were more profound. These data suggest that propofol is an effective anticonvulsant and affords a greater degree of protection than thiopentone against PTZ-induced seizures in the rat. PMID- 1625647 TI - Nosocomial infections in ventilated patients. PMID- 1625649 TI - Neurobiological disorders in children and adolescents. PMID- 1625648 TI - Anesthetic management for cesarean section in a patient with Wilson's disease. AB - We describe the successful management of a 28-year-old female with Wilson's disease who developed gestational pre-eclamptic hypertension (GPH) during pregnancy and who required an urgent cesarean delivery. We discuss the rationale of using magnesium sulphate prior to induction and the importance of adequate monitoring is selecting an anesthetic technique based on the pathophysiology of the disease. PMID- 1625650 TI - Reforming insurance law to provide equitable coverage for persons with neurobiological disorders. PMID- 1625651 TI - Obtaining insurance coverage for bipolar disorder and other neurobiological disorders on a par with other physical illnesses. PMID- 1625652 TI - Parents forced to surrender custody of children with neurobiological disorders. PMID- 1625653 TI - A free, appropriate public education for children with neurobiological disorders- sometimes available only through due process litigation. PMID- 1625654 TI - Professional supportive caring for children and adolescents with chronic neurobiological disorders. PMID- 1625655 TI - Autism. PMID- 1625656 TI - Obsessive-compulsive disorder. PMID- 1625657 TI - Bipolar disorder. PMID- 1625658 TI - Attention deficit hyperactivity disorder. PMID- 1625659 TI - Pharmacological treatment of conduct disorder. PMID- 1625660 TI - Anxiety disorders. PMID- 1625661 TI - Neuroimaging in neuropsychiatry. PMID- 1625662 TI - Brain development: pervasive developmental disorders and infantile autism. PMID- 1625663 TI - Integrating the neurobiological revolution into child and adolescent psychiatry and into society. PMID- 1625665 TI - The development of nursing research--a paradigm shift in nursing. PMID- 1625664 TI - Individualized services for children. AB - In Alaska, the development of a model of individualized services has been beneficial to children with neurobiological disorders. The AYI program has successfully demonstrated that even the most disabled children can be served in communities. This finding promotes a new level of less restrictive and more therapeutic alternatives tailored to the needs of children and their caring families. PMID- 1625666 TI - Student nurses' perceptions of experiential learning. AB - Experiential learning has been widely discussed and recommended in the nursing literature--particularly in the fields of psychiatric nursing and interpersonal skills training. This report offers some of the findings from a research study which is aimed at identifying the perceptions of student nurses towards experiential learning. 12 nursing students were interviewed and the interview transcripts were analysed using a modified grounded theory approach. Findings indicated that these students tended to see experiential learning in terms of clinical learning and learning through working in the wards and community settings. PMID- 1625667 TI - Reflective practice and nursing. AB - Reflective practice is a frequently used but in-frequently defined concept in nursing at the present time. Part of the reason for the lack of definition lies in the fact that there is no theory of practice. This paper lays the foundations for a theory of practice and paves the way for one useful way in which the relationship between theory and practice can be understood. It is suggested that thoughtful practice is often mistaken for reflective practice, but that the latter can only exist where practice is not taken for granted and so the outcome of practice is more learning from experience. The paper also maintains that for reflective practice to be practised within the profession it is necessary both to have the structures within which it can be encouraged and the theoretical foundation whereby efficient practice need not only be judged in terms of 'value for money'. PMID- 1625668 TI - Reflections of a distance education facilitator. AB - After nearly a year of preparation, 'Therapeutic Communication', the first nursing unit in our new Bachelor of Nursing degree was taught for the first time in 1988. The unit has developed and grown since this time, with both educational and financial factors determining such things as design of student materials and assessment mode. The geographically scattered--and often isolated--students are formally recognised for their individuality and their personal and professional life experiences, and given choices within the unit of what they want to learn and how they will present this material, through introduction of a learning contract as part of the unit assessment. Difficulties encountered by these students in maintaining their self-esteem when moving from the demanding and complex world of clinical nursing to the arena of tertiary study are discussed. The provision of speedy, comprehensive feedback with general as well as specific guidance with essay writing and referencing, focuses on the process skills many nurses lack as they enter this unit. The applicability of therapeutic communication to clinical practice and the diversity of projects undertaken by students within the limits of the unit demonstrate its appeal to a wide range of registered nurses. Some of the often ignored or minimised factors that differentiate external study from on-campus work are highlighted for both students and unit facilitator, and the creation of an in-house booklet to assist students in developing their skills in external study is outlined. PMID- 1625669 TI - Nursing students' learning styles: a comparison of degree and non-degree student approaches to studying. AB - This research utilised the Lancaster inventory to investigate the approaches to studying of a group of nurse learners (n = 32) from a college of nursing and midwifery and a group of nursing undergraduates (n = 23) from an institution of higher education. It was hoped that the research would cast some light on whether the two groups approach their studying in similar or different ways, since these approaches may dictate success in educational ventures. The results indicated no statistically significant differences between the two learner groups' approaches to studying. PMID- 1625670 TI - Interaction in the classroom: district nurse students and their teachers. AB - This research project aimed to investigate interaction in the classroom between district nurse students and their teachers and to identify some characteristics of effective teaching and learning. The research explored events in the classroom and relationships between students and teachers, and students and their peers. Symbolic Interactionism was used as the theoretical framework. Ethnographic methods within qualitative research focused on the ways in which teachers and students organise themselves and their environment through roles, rules and procedures. PMID- 1625671 TI - Knowledge about, and attitudes to, HIV/AIDS among students in a Sydney nursing college. AB - The purpose of this study was to assess nursing students' knowledge about HIV infection and AIDS. 231 nursing students at a nursing college in Sydney were invited, and agreed, to participate. They were surveyed on knowledge about transmission, precautions to take when providing nursing care and epidemiology, general attitudes to HIV/AIDS, attitudes to patient-care, risk of infection at work and homosexuality. Two knowledge and four attitude scales were constructed. The students showed a fairly high level of knowledge: a mean percentage score of 78 on the transmission scale and 80 on the precaution scale. They also had some misconceptions about transmission routes. A majority (72%) had favourable attitudes to AIDS patient care; a minority (22%) had a clear fear of contagion through occupational exposure; 26% had negative attitudes to homosexuality. Nursing students with AIDS-care experience had significantly more positive attitudes than those who had no such experience. Knowledge and attitudes were positively correlated (correlation range 0.24-0.46). It is suggested that training programmes include experiential learning to address fear, discomfort and anxieties about HIV/AIDS. PMID- 1625672 TI - AIDS counselling and nurse education. AB - The number of people with AIDS and HIV related disorders is increasing. Nurses are going to be called, increasingly, to act as AIDS counsellors. This paper explores some of the issues involved in counselling people with AIDS and some of the related literature. It suggests that any course for helping nurses to develop such skills will involve at least the following elements: information, values clarification and basic counselling skills. PMID- 1625673 TI - APL: a corporate strategy. AB - This paper is based on, and summarises, papers read at the second annual international conference of Nurse Education Tomorrow held at the University of Durham (UK) September 1991. To this end this paper will offer: Some Accreditation of Prior Learning (APL) definition and process as reflected in the literature available. A distinction will be made between APL and Accreditation of Prior Experiential Learning (APEL) although the procedures and processes for assessing them will be shown to be the same. A brief outline of corporate strategy, as it applies to APL, will be given to form the basis for logical demonstration of how Derbyshire Institute of Health and Community Studies has employed such a corporate strategy. Insights developed and gained from APL research currently being undertaken through the college of nursing and midwifery will be used to inform the development and nature of corporate strategy. A flowchart of the operationalisation of the corporate strategy is offered as an integrative summary of how all the APL ideas have had a positive cumulative effect. The paper finishes by highlighting the possible strengths and limitations of APL corporate strategy. PMID- 1625674 TI - The nurse teacher's role in the practice setting. AB - In the light of the education reforms brought about by the implementation of Project 2000 it is essential that nurse teachers critically appraise their role and function. In particular, they need to give careful consideration to their role in relation to the practice setting. Whilst the English National Board (1989) indicate that nurse teachers should retain their clinical competence and be able to teach in both classroom and practice settings, little has been written in respect of the implications of this directive. This paper considers the issue of clinical competence and explore some of the different dimensions of the nurse teacher's role in the practice setting, in respect of teaching, providing educational support and facilitating good practice. Finally, some of the issues relating to the successful fulfilment of this role are identified for consideration. PMID- 1625675 TI - Getting there by degree . . . a personal view of undertaking a part-time degree course. AB - Nine months ago the author became a student on a part-time Bachelor of Nursing Sciences Course. The author shares her experience in order to encourage nurses to consider undertaking this type of study and at the same time persuade course selector that part-time workers with domestic commitments can cope. PMID- 1625677 TI - Effects of phorbol esters on insulin receptor function and insulin action in hepatocytes: evidence for heterogeneity. AB - We investigated the effect of phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator on insulin receptors and insulin action in freshly isolated and primary cultures of rat hepatocytes. PMA (1 x 10(-7) M) did not alter insulin receptor numbers or affinity either acutely or chronically but within 60 minute inactivated insulin stimulated tyrosine kinase of the insulin receptor. PKC activation inhibited insulin (1 x 10(-7) M) stimulation of glycogen and lipid synthesis with a decrease or no change in basal glycogenesis and lipogenesis respectively. However, PKC activation did not alter insulin stimulated or basal amino acid transport even though PKC activation inhibited insulin stimulation of the insulin receptor tyrosine kinase. Thus, within one tissue, PKC activation has differential effect on insulin action depending on which pathway is examined. Furthermore, insulin stimulation of the insulin receptor tyrosine kinase may not be a necessary step for all insulin signaling pathways. PMID- 1625676 TI - Approaches to the molecular cloning of protein-tyrosine phosphatases in insulin sensitive tissues. AB - The intrinsic tyrosyl kinase activity of the insulin receptor is regulated by a balance between insulin-induced receptor autophosphorylation, which stimulates the receptor kinase, and enzymatic dephosphorylation of the receptor, which deactivates its kinase activity. The cellular protein-tyrosine phosphatase (PTPase) enzymes responsible for reversing the activated state of the insulin receptor have not been characterized. Our laboratory is interested in identifying and cloning the specific PTPase(s) that regulate the phosphorylation state of the insulin receptor. This chapter will summarize the design and results of our initial molecular cloning studies to identify specific PTPases in insulin sensitive tissues that may have a potential physiological role in insulin action and clinical insulin resistance. PMID- 1625678 TI - Insulin resistance and hypertension. PMID- 1625679 TI - Comparative effects of 6 week fructose, dextrose and starch feeding on fat-cell lipolysis in normal rats: effects of isoproterenol, theophylline and insulin. AB - The precise effects of fructose feeding on adipose tissue is not clearly known. Consequently, we studied the effects of fructose feeding on stimulated and inhibited in vitro lipolysis. Twenty seven male Sprague Dawley rats, 5 weeks of age, were fed for 6 weeks on one of three diets containing 57% CHO as fructose (F), dextrose (D) or starch (S). At week 6 the epididymal fat pad weights showed no difference between groups. Stimulation of lipolysis by isoproterenol or theophylline showed: decreased sensitivity of adipocytes to isoproterenol, but not to theophylline, in F (p less than 0.05); the maximal responses were decreased, but NS, after stimulation by either isoproterenol or theophylline. The maximal antilipolytic responses to insulin were increased in F (27%) and D (29%) when compared to S (16%), (p less than 0.05). Only, in F there was an increase (NS) in ED50 (0.63 +/- 0.23 ng/ml) compared to D (0.45 +/- 0.18) and S (0.29 +/- 0.18), indicating decreased sensitivity. Nonfasting plasma insulin and triglycerides were increased at the 6th week in F (p less than 0.01), without any change in plasma glucose levels. However, there was no difference in 12 h fasting plasma glucose, insulin or triglycerides. In conclusion, a 6 week 57% fructose containing diet in normal rats led to: 1) decreased lipid mobilization in the epididymal adipose tissue; and 2) increased nonfasting plasma insulin and triglycerides. Thus fructose, under these experimental conditions, seems to have adverse metabolic effects in normal rats. PMID- 1625680 TI - Vanadate induces the recruitment of GLUT-4 glucose transporter to the plasma membrane of rat adipocytes. AB - In rat adipocytes, the insulin stimulation of the rate of glucose uptake is due, at least partially, to the recruitment of glucose transporter proteins from an intracellular compartment to the plasma membrane. Vanadate is a known insulin mimetic agent and causes an increase in the rate of glucose transport in rat adipocytes similar to that seen with insulin. The objective of the present study was to determine whether vanadate exerts its effect through the recruitment of glucose transporters to the plasma membrane. We report that under conditions where vanadate stimulates the rate of 2-deoxyglucose uptake to the same extent as insulin, the concentration of GLUT-4 in the plasma membrane was increased similarly by both insulin and vanadate, and its concentration was decreased in the low density microsomal fraction. These results suggest that vanadate induces the recruitment of GLUT-4 to the plasma membrane. The effects of vanadate and insulin on the stimulation of 2-deoxyglucose uptake and recruitment of GLUT-4 were not additive. This is the first report of an effect of vanadate on the intracellular distribution of the glucose transporter. PMID- 1625681 TI - The effects of orthovanadate, vanadyl and peroxides of vanadate on glucose metabolism in skeletal muscle preparations in vitro. AB - The insulin-like effects of various vanadium compounds (orthovanadate, vanadyl and peroxides of vanadate) on rates of glucose oxidation, lactate formation and glycogen synthesis were measured in isolated incubated epitrochlearis (mainly type II fibres) and soleus (mainly type I fibres) muscle preparations. There was a small stimulation of the rate of glucose utilisation in soleus muscle preparations in vitro by orthovanadate (1 mM). Orthovanadate or vanadyl, at 1 mM, had little effect on the rates of lactate formation or glycogen synthesis in isolated incubated epitrochlearis muscle preparations. In contrast, peroxides of vanadate (peroxovanadates, at 1 mM) significantly stimulated glucose utilisation in both soleus and epitrochlearis muscle preparations in vitro. The stimulation of the rate of glycogen synthesis was associated with an increase in the percentage of glycogen synthase in the I (or a) form. Peroxovanadates were administered in the drinking water to rats made insulin deficient by streptozotocin treatment. There was no decrease in the elevated level of blood glucose over an 8 day administration period. PMID- 1625683 TI - Impairment of contractility associated with muscarinic supersensitivity in trachea isolated from diabetic rats: lack of correlation with ultrastructural changes or quinuclidinyl benzylate binding to lung membranes. AB - Evolution of cholinergic response of rat isolated trachea was determined after various durations of diabetes (17, 40, 90, 150 and 210 days). Long-term diabetes was associated with both impairment of contractility and supersensitivity to cholinergic stimulation. However, the mechanism of these alterations remains to be determined, as response to field stimulation was not specifically altered while electron microscopy studies could not detect any significant change in the aspect of nerves, smooth muscle or epithelium. As well, binding studies of lung cholinergic receptors using the antagonist ligand [3H]-quinuclidinyl benzylate and the agonist carbachol did not detect any change in diabetic animals. PMID- 1625682 TI - Effects of vanadyl derivatives on animal models of diabetes. PMID- 1625684 TI - Serum lipids and urinary albumin excretion in non insulin-dependent diabetics. AB - The increase of urinary albumin excretion has a predictive value for cardiovascular disease in insulin-dependent and non insulin-dependent diabetics. To study the relationship between urinary albumin excretion and serum lipids, 380 non insulin-dependent diabetics, 40 to 75 yr old, with urinary albumin excretion from 0 to 200 mg/l, and normal serum creatinine (less than 150 mumol/l), were surveyed. Urinary albumin excretion, was related positively to age (r2 = 0.014; p = 0.02), to systolic blood pressure (r2 = 0.073, p = 0.0001) and diastolic blood pressure (r2 = 0.052, p = 0.0001); a negative correlation existed with HDL cholesterol (r2 = 0.043, p = 0.0001) and Apoprotein A1 (r2 = 0.044, p = 0.0001). A stepwise regression analysis was performed and resulted in three independently contributing variables related to urinary albumin excretion: First systolic blood pressure (F = 36), second Apoprotein A1 (F 24), third hemoglobin A1C (F = 6). The presence of hypertension or insulin therapy did not modify these findings. In conclusion, serum lipid seems an important determinant of urinary albumin excretion in non insulin-dependent diabetics. PMID- 1625685 TI - Models of insulin action on metabolic and growth response genes. AB - In ongoing studies aimed at elucidating the mechanism of insulin action on the expression of genes that modulate glucose utilization and cell growth, we have focused on the inductive effect of insulin on transcription of glyceraldehyde-3 phosphate dehydrogenase (GAPDH) and the early growth response gene, Egr-1. Insulin acutely stimulates the expression of both genes in 3T3 adipocytes; however, in primary adipocytes, chronic insulin exposure has opposing effects on the expression of these genes. GAPDH mRNA is decreased in the epididymal fat cells of diabetic animals and is increased over control levels when insulin is replaced, while Egr-1 mRNA levels are increased in diabetic animals. These observations, coupled with the finding that insulin-stimulated Egr-1 gene transcription is impaired in a Chinese hamster ovarian (CHO) cell line that displays normal metabolic responses but impaired ability to regulate DNA synthesis, support the conclusion that insulin regulation of Egr-1, a growth response gene, and GAPDH, a metabolic response gene, are mediated by distinct pathways. We present evidence that supports the role of protein phosphorylation in mediating the effect of insulin on activation of Egr-1 and GAPDH gene transcription. PMID- 1625686 TI - Link studied between maternal behaviors, pregnancy outcome. PMID- 1625687 TI - FDA panel recommends restricted use of breast implants. PMID- 1625688 TI - New organization targets carnitine deficiency. PMID- 1625689 TI - What is the difference between diagnostic mammography and screening mammography? PMID- 1625690 TI - NAACOG position statement. Issue: the HIV-infected health-care worker. PMID- 1625691 TI - Nursing intervention with battered women. Abuse often increases with pregnancy. PMID- 1625693 TI - Clinical issues studies neonates with low birth weights. PMID- 1625692 TI - What drugs are used to prevent and treat chlamydial eye infections in newborns? PMID- 1625694 TI - As breast cancer rates rise, nurses' role increases. PMID- 1625695 TI - What is the role of pelvic muscle exercise (PME) in the prevention and treatment of stress urinary incontinence (SUI)? PMID- 1625696 TI - FDA limits access to breast implants. PMID- 1625697 TI - Mechanistic studies in the transcuticular delivery of antiparasitic drugs. II: Ex vivo/in vitro correlation of solute transport by Ascaris suum. AB - Using live, intact Ascaris suum and a closed perfusion system, the absorption kinetics and tissue distribution of selected radiolabeled permeants were measured to determine the importance of the transcuticular pathway for drug absorption. The data support the conclusions established by previous in vitro transport studies which utilized excised cuticle-hypocuticle tissue preparations. The external surface of A. suum can be breached by drugs and the rate-determining barrier is the lipoidal hypocuticle tissue, provided the permeant is sufficiently small to traverse the aqueous-filled, negatively charged collagen matrix of the cuticle. The ex vivo permeability coefficients of the model permeants for the cuticle-hypocuticle barrier were in good quantitative agreement with the in vitro permeability coefficients. The lipophilic permeants hydrocortisone and p nitrophenol were preferentially distributed in the gut tissue, whereas the hydrophilic permeant urea was distributed evenly throughout the organism and was extensively metabolized. Ligated and nonligated A. suum showed no significant differences in either uptake kinetics or tissue distribution of the permeants. This indicates that the transcuticular pathway is the major route of drug absorption as compared to oral ingestion. PMID- 1625698 TI - A potential hexose transporter gene expressed predominantly in the bloodstream form of Trypanosoma brucei. AB - A cDNA cloned from Trypanosoma brucei brucei codes for a putative membrane protein which is homologous to the erythrocyte glucose transporter and several other sugar transporters from Escherichia coli, yeast, algae and Leishmania. This cDNA hybridizes to a 2.3-kb mRNA that accumulates to a much higher degree in the bloodstream mammalian form than in the procyclic insect form of the parasite. The correlation between the expression of this gene and the hexose metabolism of Leishmania enriettii and T. brucei suggest that these 2 related genes probably encode hexose transporters. The gene encoding this mRNA is a member of a multigene family. The putative hexose transporter gene is highly conserved among Kinetoplastidae, indicating an important role for this protein in the parasite life cycle. PMID- 1625699 TI - Chromosomes of Babesia bovis and Babesia bigemina. PMID- 1625700 TI - Molecular cloning and sequencing of glutathione peroxidase from Schistosoma mansoni. PMID- 1625701 TI - Cloning and characterization of the Wuchereria bancrofti S15 ribosomal protein. PMID- 1625702 TI - Cloning and sequence analysis of a calcium-binding protein gene from a pathogenic strain of Entamoeba histolytica. PMID- 1625703 TI - The protein sequence predicted from a Leishmania guyanensis gp63 major surface glycoprotein gene is divergent as compared with other Leishmania species. PMID- 1625704 TI - Stage-specific expression of aldolase isoenzymes in the rodent malaria parasite Plasmodium berghei. AB - We have cloned two gene (aldo-1 and aldo-2) encoding the glycolytic enzyme aldolase of the rodent malaria parasite Plasmodium berghei. The amino acid sequence of one gene product, ALDO-1, is virtually identical to P. falciparum aldolase whereas ALDO-2, the second gene product, is different and has 13% sequence diversity to ALDO-1. We expressed ALDO-2 as an active enzyme in Escherichia coli and compared the biochemical and kinetic properties to that of P. falciparum recombinant aldolase (ALDO-1 type). Based on the Km and Vmax constants for FMP and FBP, neither ALDO-1 nor ALDO-2 can be clearly assigned to any of the known mammalian isoenzyme classes. We demonstrate that expression of the two isoenzymes is developmentally regulated: specific antibody probes detect ALDO-1 in sporozoite stages of P. berghei and ALDO-2 is found in blood stage parasites. PMID- 1625705 TI - Active site thiol(s) in Leishmania donovani adenosine kinase: comparison with hamster enzyme and evidence for the absence of regulatory adenosine binding site. AB - Adenosine kinase (ATP, adenosine 5'-phosphotransferase, E.C. 2.7.1.20) from Leishmania donovani, unlike adenosine kinase from other known eukaryotic sources, does not elicit an inhibitory response at high concentrations of adenosine. The mechanistic basis for this unique catalytic behavior of the parasite enzyme has been probed with the help of chemical modification and enzyme inhibition kinetics experiments. The use of cysteine-directed reagents has shown that chemical integrity of cysteinyl residues is essential for the expression of functional activity of the enzyme. Thiol group titration revealed that the enzyme contains 3 cysteine residues. However, in contrast to adenosine kinase from other sources, inactivation of the parasite enzyme could be correlated with alkylation of 2 cysteinyl residues. Adenosine, but not ATP, protected 2 thiols against -SH blocker-mediated inactivation of the enzyme. The thiol groups were shown to map at positions corresponding to approximately 16, 22, and 36 kDa sites from the protein's N-terminal end. The functions of 2 thiols at the catalytic site were functional thiol groups yielded a 'protection constant' (KpAd) of 3.4 microM, while the dissociation constant (KsAD) of the enzyme-substrate complex was 2.7 microM, hence supporting involvement of the same in both processes, namely catalysis and protection. The overall results were therefore interpreted as showing that (a) the leishmanial enzyme, in contrast to adenosine kinase from other sources, contains 2 functional thiol groups at the catalytic site; and (b) the enzyme binds adenosine exclusively through the catalytic site and as a consequence is not amenable to inhibition at high adenosine concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1625706 TI - Schistosoma mansoni p48 eggshell protein gene: characterization, developmentally regulated expression and comparison to the p14 eggshell protein gene. AB - Egg production by worm pairs is a major cause of pathogenesis in schistosomiasis. To further the understanding of female reproductive development, we have isolated and characterized a complete copy of an eggshell protein precursor gene, p48. Sequence analysis reveals that the gene has 3 open reading frames and does not contain an intron. One of the open reading frames, ORF1, encodes a polypeptide of 50 kDa which shows strong homology to insect chorion proteins. Determination of the position of the mRNA cap-site facilitated identification of putative regulatory elements in the 5' upstream region of the gene. Some of these elements (e.g., TCACGT) have been shown to play a role in the regulation of chorion gene expression in insects. p48 mRNA is detectable only in mature female worms and the ability to detect the mRNA coincides temporally with worm pairing. Quantitative comparisons, during female reproductive development, of p48 transcripts to those from another eggshell protein precursor gene, p14, show that the p48 mRNA is significantly less abundant than p14 mRNA. In mature female worms, p48 mRNA can only be detected in vitelline cells. Antibodies made against the polypeptide sequence deduced from ORF1 of the p48 gene recognize a 50-kDa molecule in extracts from mature female worms, but not in extracts from immature females or males. PMID- 1625707 TI - Chitinase activity in encysting Entamoeba invadens and its inhibition by allosamidin. AB - Chitinase activity was measured in extracts of Entamoeba invadens cells as a function of time of encystation in axenic conditions using 4-MU(Ch)3 as substrate. Encystment was paralleled by chitinase activity which showed a peak after about 72 h of cultivation where cysts accounted for 63% of cell population. Thereafter, activity fell off rapidly, whereas encystment continued, reaching 80% at the end of the experiment (96 h). Comparison of activity between cysts and the total cell population in 48- and 72-h-old encysting cultures suggested that chitinase may start to accumulate in the pre-cyst forms. About 70% of the enzyme was recovered in the supernatant following low-speed centrifugation of whole extracts. Most of this activity represented soluble chitinase since it was not sedimented by further centrifugation at 105,000 x g. A minor proportion of enzyme activity remained associated to the buffer-washed, high-speed sediment. In addition to 4-MU(Ch)3, chitinase activity was also measured following the hydrolysis of other substrates such as nascent, preformed or colloidal chitin. Like other chitinases, the cyst enzyme preferred nascent over preformed chitin as substrate. Digestion of the former yielded GlcNAc and minor amounts of (GlcNAc)2 as products. Allosamidin strongly inhibited hydrolysis of the fluorogenic substrate by the amebic chitinase in vitro with a Ki of 0.065 microM. IC50 values were 0.085 microM and 0.16 microM at 5 microM and 10 microM 4-MU(Ch)3, respectively. When added to the axenic medium, the drug markedly retarded encystment though it was partially recovered after longer periods of incubation. PMID- 1625708 TI - Changes in the surface composition after transmission of Acanthocheilonema viteae third stage larvae into the jird. AB - This study describes the dynamics and the biochemical nature of changes in the surface of the filarial nematode Acanthocheilonema viteae after its transmission into the vertebrate host. Vector-derived third-stage larvae (mL3) were inoculated into naive Meriones unguiculatus and recovered from the tissues at different times post-infection until their moult to fourth-stage larvae (L4). Surface specific labelling with fluoresceinated lectins revealed that the larvae are covered by a carbohydrate envelope. Although the mL3 envelope was strongly reduced one day after transmission, new surface carbohydrates appeared until the onset of moulting, some of which could also be identified on the surface of L4. In general, surface carbohydrates were partially shed by moving larvae, suggesting a loose association of these components in the epicuticle. The fate of cuticular lipids and proteins of L3 and L4 was monitored by external 125I labelling and differential extraction of the components. Thin-layer chromatography of surface-labelled lipids revealed only minor changes 1 day after parasite transmission. Afterwards the number of lipids accessible to label decreased further until moulting was complete. Two-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis of surface-labelled proteins showed a consistent surface exposure of mL3 specific proteins until 1 day post-infection. Thereafter, the composition of surface-labelled proteins changed rapidly, resembling that of the L4 as early as several days before moulting. During this period individual differences in the composition of surface proteins were evident. PMID- 1625709 TI - Characterization of the rDNA unit and sequence analysis of the small subunit rRNA and 5.8S rRNA genes from Tritrichomonas foetus. AB - The ribosomal RNA gene unit of the protozoan parasite Tritrichomonas foetus has been cloned and analyzed. Southern blot analysis of the genomic DNA showed that the ribosomal RNA gene unit is organized as a tandem head to tail repeat with a unit length of 6 kb. By Northern analysis a primary transcript of 5.8 kb was detected. Copy number analysis showed the presence of 12 copies of the ribosomal RNA gene unit. The lengths of the small subunit ribosomal RNA and 5.8S ribosomal RNA are 1571 bp and 159 bp, respectively, as determined by sequence analysis. The T. foetus small subunit ribosomal RNA sequence is one of the shortest eukaryotic small subunit rRNA sequences, similar in length to those from 2 other amitochondrial protists. Although shorter than the majority of the eukaryotic small subunit ribosomal RNAs, this sequence maintains the primary and secondary structure common to all eukaryotic small subunit ribosomal RNA structures, while truncating sequences found within the eukaryotic variable regions. The length of the large subunit ribosomal RNA was measured at 2.5 kb. PMID- 1625710 TI - Surface-associated antigens of Brugia malayi L2 and L3 parasites during vector stage development. AB - Surface and metabolic labeling procedures were used to characterize the composition and the time of expression of Brugia malayi L2 and L3 surface associated molecules as the larvae develop within the mosquito vector. Larvae were harvested from mosquito tissues at 5 (early L2), 8 (late L2) and 11 (L3) days post-infection and labeled with 125I-Iodo-Gen. The results of one dimensional analysis showed that there is a progressive increase in the complexity of peptides associated with the surface of developing larvae, culminating in the expression of 7 major labeled components on L3s. Both L2 and L3 parasites have surface-associated components of 42, 35, 33, 19 and 17 kDa. Between days 8 and 11 of development in the insect vector, Brugia malayi undergoes the L2 to L3 molt and acquires additional major immunogenic peptides of 40 and 22 kDa. Two-dimensional analyses of extracts from 125I-labeled L2s and L3s revealed that the major 35-, 33-, 19- and 17-kDa molecules are part of a peptide complex that forms a 'ladder' between 17 and 150 kDa. To gain information on the times during which the major surface-associated molecules are produced by the parasite, larvae were labeled with [35S]methionine either in situ as they developed within the mosquito or during culture after exiting the vector. For in situ labeling, [35S]methionine was introduced into the hemolymph of infected mosquitoes by micro-injection at days 2, 5 and 8 post-infection and the larvae were allowed to develop for an additional 3 days. The results of 1- and 2 dimensional analyses of [35S]methionine-labeled extracts from vector-stage or post-vector-stage larvae indicate that the molecules associated with the surface of B. malayi L3s are synthesized between day 5 and day 11 of development in the insect host. Immediately after the larvae exit the vector, the synthesis of the 40 and 22-kDa peptides is drastically reduced or terminated. PMID- 1625711 TI - Mitral annular calcification and the risk of stroke in an elderly cohort. AB - BACKGROUND: Previous clinical studies have suggested that there is an association between mitral annular calcification and the risk of stroke, but it is unclear whether this association is independent of the traditional risk factors for stroke. We examined the relation between mitral annular calcification and the incidence of stroke in a population-based study. METHODS: Subjects in the Framingham Study receiving a routine examination underwent M-mode echocardiography to determine the presence and severity (thickness in millimeters) of mitral annular calcification. The incidence of stroke during eight years of follow-up was analyzed with a proportional-hazards model adjusting for the calcification, age, sex, systolic blood pressure, diabetes mellitus, cigarette smoking, atrial fibrillation, and coronary heart disease or congestive heart failure. RESULTS: Among 1159 subjects whose echocardiograms could be assessed for mitral annular calcification and who had no history or current evidence of stroke at the index examination (51 percent of all subjects), the prevalence of mitral annular calcification was 10.3 percent in the men and 15.8 percent in the women. Multivariate analysis demonstrated that the presence of mitral annular calcification was associated with a relative risk of stroke of 2.10 (95 percent confidence interval, 1.24 to 3.57; P = 0.006). There was a continuous relation between the incidence of stroke and the severity of mitral annular calcification; each millimeter of thickening as shown on the echocardiogram represented a relative risk of stroke of 1.24 (95 percent confidence interval, 1.12 to 1.37; P less than 0.001). Furthermore, even when subjects with coronary heart disease or congestive heart failure were excluded from the analysis, subjects with mitral annular calcification still had twice the risk of stroke. CONCLUSIONS: In an elderly, longitudinally followed population based cohort, mitral annular calcification was associated with a doubled risk of stroke, independently of traditional risk factors for stroke. Whether such calcification contributes causally to the risk of stroke or is merely a marker of increased risk because of its association with other precursors of stroke remains unknown. PMID- 1625712 TI - Brief report: severe symptoms of hyperhistaminemia after the treatment of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid) PMID- 1625713 TI - Brief report: kidney-related Munchausen's syndrome. PMID- 1625714 TI - Effect of cocaine use on the fetus. PMID- 1625715 TI - The Red Baron. PMID- 1625716 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 32-1992. A 72-year-old man with a mass in the posterior thigh. PMID- 1625717 TI - The risk of transfusion-transmitted infection. PMID- 1625718 TI - Lethal food allergy in children. PMID- 1625719 TI - The maturation of differentiation therapy. PMID- 1625720 TI - Gatekeeping revisited--protecting patients from overtreatment. PMID- 1625721 TI - Cancer in the contralateral breast after radiotherapy for breast cancer. PMID- 1625722 TI - Cancer in the contralateral breast after radiotherapy for breast cancer. PMID- 1625723 TI - Cancer in the contralateral breast after radiotherapy for breast cancer. PMID- 1625724 TI - Cancer in the contralateral breast after radiotherapy for breast cancer. PMID- 1625725 TI - Monoclonality of multiple bladder cancers. PMID- 1625726 TI - Monoclonality of multiple bladder cancers. PMID- 1625727 TI - Screening sigmoidoscopy and colorectal cancer. PMID- 1625728 TI - Partner notification in cases of HIV infection. PMID- 1625729 TI - Partner notification in cases of HIV infection. PMID- 1625730 TI - Pneumococcal vaccine for Olympic athletes and visitors to Spain. Barcelona Olympic Organizing Committee. PMID- 1625731 TI - Functional asplenia and vasculitis associated with antineutrophil cytoplasmic antibodies. PMID- 1625732 TI - The American health care system--introduction. PMID- 1625733 TI - Factitious Munchausen's syndrome--a confession. PMID- 1625734 TI - HIV infection among patients in U.S. acute care hospitals. Strategies for the counseling and testing of the hospital patients. The Hospital HIV Surveillance Group. AB - BACKGROUND: Routine, voluntary testing of hospital patients for the human immunodeficiency virus (HIV) has been proposed in order to identify those with early HIV infection in a setting where there is ready access to counseling, appropriate clinical referral, evaluation, and therapy. We studied the pattern of HIV infection among patients in 20 U.S. hospitals, in order to evaluate possible national strategies for the routine, voluntary HIV counseling and testing of hospital patients. METHODS: Blood specimens remaining after clinical use from a systematically selected sample of patients at 20 hospitals in 15 U.S. cities were tested anonymously for antibody to HIV type 1 (HIV-1). Multivariate regression was used to determine which variables best predicted HIV seroprevalence in individual hospitals. Using these data, we estimated the number of HIV-positive patients in all U.S. hospitals and considered the efficiency of routine counseling and testing in different subgroups of patients and hospitals. RESULTS: From September 1989 through October 1991, 9286 of 195,829 specimens (4.7 percent) were positive for HIV-1 in the 20 hospitals. The seroprevalence of HIV at these institutions ranged from 0.2 percent to 14.2 percent. Among HIV-positive patients, 32 percent had symptomatic HIV infection or the acquired immunodeficiency syndrome (AIDS) at the time of admission or evaluation. In the 20 hospitals, HIV seroprevalence was 10.4 times (95 percent confidence interval, 8.8 to 12.0) the AIDS-diagnosis rate (the annual number of patients with new diagnoses of AIDS per 1000 discharges in 1990). In a multivariate model that included 13 hospital-specific variables, only the AIDS-diagnosis rate was associated with the hospital-specific HIV-seroprevalence rate (P less than 0.001). Using these data and the AIDS-diagnosis rates for all U.S. acute care hospitals, we estimated that 225,000 HIV-positive persons were hospitalized (95 percent confidence interval, 190,000 to 260,000) in all 5558 such hospitals in 1990, including 163,000 persons presenting with conditions other than HIV or AIDS (95 percent confidence interval, 130,000 to 196,000). In 1990, in 593 U.S. hospitals with AIDS-diagnosis rates of 1.0 or more per 1000 discharges, HIV testing of patients 15 to 54 years old (3 million patients, or 12.0 percent of all patients in U.S. acute care hospitals) would have identified an estimated 68 percent of all HIV-positive patients (110,000 patients) who were admitted with conditions other than symptomatic HIV infection or AIDS. CONCLUSIONS: We estimate that about 225,000 HIV-positive persons were hospitalized in 1990, of whom only one third were admitted for symptomatic HIV infection or AIDS. Routine, voluntary HIV testing of patients 15 to 54 years old in hospitals with 1 or more patients with newly diagnosed AIDS per 1000 discharges per year could potentially have identified as many as 110,000 patients with HIV infection that was previously unrecognized. PMID- 1625735 TI - Implications of third heart sounds in patients with valvular heart disease. The Veterans Affairs Cooperative Study on Valvular Heart Disease. AB - BACKGROUND: The presence of third heart sounds in patients with valvular heart disease is often regarded as a sign of heart failure, but it may also depend on the type of valvular disease. METHODS: We assessed the prevalence of third heart sounds and the relation between third heart sounds and cardiac function in 1281 patients with six types of valvular heart disease. RESULTS: The prevalence of third heart sounds was higher in patients with mitral regurgitation (46 percent) or aortic regurgitation (28 percent) than in those with aortic stenosis (11 percent) or mitral stenosis (8 percent). The left ventricular ejection fraction was significantly lower (P less than 0.001) when a third heart sound was detected in patients with aortic stenosis (0.38, vs. 0.56 in those without third heart sounds) or mixed aortic valve disease (0.40 vs. 0.55). However, the ejection fraction was only slightly lower in patients with mitral regurgitation and third heart sounds (0.51 vs. 0.57, P = 0.03). The pulmonary-capillary wedge pressure was higher (P less than 0.001) when a third heart sound was detected in patients with aortic stenosis (18.6 mm Hg, vs. 12.1 mm Hg in those without third heart sounds). There was no association between the wedge pressure and third heart sounds in patients with mitral regurgitation. The prevalence of third heart sounds increased with the severity of mitral regurgitation. CONCLUSIONS: In patients with mitral regurgitation, third heart sounds are common but do not necessarily reflect left ventricular systolic dysfunction or increased filling pressure. In patients with aortic stenosis, third heart sounds are uncommon but usually indicate the presence of systolic dysfunction and elevated filling pressure. PMID- 1625736 TI - Elevated arterial blood pressure in cardiac tamponade. AB - BACKGROUND: In cardiac tamponade cardiac output falls, but peripheral vascular resistance increases, so that systemic blood pressure may be maintained at normal or near-normal levels. We recently observed a patient with cardiac tamponade whose blood pressure was markedly elevated. METHODS: To determine the frequency of elevated blood pressure in patients with cardiac tamponade and their hemodynamic characteristics, we studied 18 consecutive patients with cardiac tamponade from a variety of causes using right heart catheterization. RESULTS: Six of the 18 patients had systolic arterial blood pressures ranging from 150 to 210 mm Hg (mean [+/- SD], 176 +/- 26) and diastolic pressures ranging from 100 to 130 mm Hg (mean, 113 +/- 14). All six had previously been hypertensive. After pericardiocentesis there was a significant decrease in blood pressure (to 139 +/- 13 mm Hg systolic, P less than 0.05; and 83 +/- 6 mm Hg diastolic, P less than 0.01) and peripheral vascular resistance (from 2150 +/- 588 to 1207 +/- 345 dyn.sec.cm-5, P less than 0.01). Cardiac output increased in all six. The other 12 patients, 3 of whom had a history of hypertension, had significant increases in cardiac output and systolic blood pressure (from 119 +/- 13 to 127 +/- 7 mm Hg, P less than 0.05) after pericardiocentesis, whereas peripheral vascular resistance decreased. Both groups had similar degrees of cardiac tamponade, as indicated by measurements of cardiac output and intrapericardial, right atrial, and pulmonary-artery wedge pressures. CONCLUSIONS: Elevated blood pressure may occur in some patients with cardiac tamponade who have preexisting hypertension. Moreover, blood pressure may fall after pericardiocentesis in patients who have elevated blood pressure associated with tamponade. PMID- 1625737 TI - Breast cancer (3). PMID- 1625738 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 33-1992. A 34-year-old woman with endometriosis and bilateral hydronephrosis. PMID- 1625739 TI - Screening for HIV infection--benefits and costs. PMID- 1625740 TI - AIDS and absolutism--the demand for perfection in prevention. PMID- 1625741 TI - Transmission of hepatitis B by a finger-stick device. PMID- 1625742 TI - Transmission of hepatitis B by a finger-stick device. PMID- 1625743 TI - Transmission of hepatitis B by a finger-stick device. PMID- 1625744 TI - Pneumocystis carinii pneumonia during cyclosporine therapy for ulcerative colitis. PMID- 1625745 TI - Allopurinol in the treatment of American cutaneous leishmaniasis. PMID- 1625746 TI - Hodgkin's disease. PMID- 1625747 TI - Hodgkin's disease. PMID- 1625748 TI - Successful thrombolysis of an aortic-arch thrombus in a patient after mesenteric embolism. PMID- 1625749 TI - The Guillain-Barre syndrome. PMID- 1625750 TI - AIDS and activists. PMID- 1625751 TI - AIDS and activists. PMID- 1625752 TI - Newspaper reports and suicide. PMID- 1625753 TI - The bite of the spider woman. Loxosceles reclusa (the brown recluse). PMID- 1625754 TI - Does a demented patient lose the right to refuse surgical intervention? PMID- 1625755 TI - Pott's disease revisited. Paravertebral abscess extending into the right lower extremity. PMID- 1625756 TI - Epilepsy--diagnosis and treatment. AB - In summary, a better understanding of seizures, seizure disorders and epilepsy syndromes, as well as the advent of effective medications with generally low toxicity and side effects, now enables most epileptics to lead relatively normal lives. Careful analysis of seizure type, accurate prescription of appropriate medication and precise monitoring of medication are essential. The prognosis of, and lifestyle enjoyed by, individuals with epilepsy is far less grim than the image conjured up in the mind of the average, uninformed person on the street. Prejudice and misunderstanding still exist, however, and further public education and awareness are appropriate goals for the future. PMID- 1625757 TI - Health care of the homeless in the British National Health Service. PMID- 1625758 TI - Diabetes education. An idea whose time has come. PMID- 1625759 TI - Auditing the clinical learning environment in West Glamorgan: evaluating the process. AB - The responsibility for auditing clinical learner areas was developed from the Welsh National Board to individual educational establishments in Wales in 1988. The West Glamorgan College of Nursing and Midwifery designed on audit tool, based on the National Board's guidelines, and have used it in clinical areas since 1990. This paper reports on an evaluation survey carried out after the tool had been in use for one year. The results suggest that the ward/area managers involved have been able to identify a range of benefits for their units with the introduction of the tool, and demonstrate an acceptance of the need to maintain standards of practice and education. PMID- 1625760 TI - A trial of the use of psychodrama for women with alcohol problems. AB - Psychodrama is a method of group psychotherapy in which the subject can be helped to explore the psychological dimensions of his or her problems through the enactment of conflict situations. This study aimed to investigate the perceived effectiveness of psychodrama in the treatment of women with alcohol problems. A group of six women undertaking psychodrama in a centre in Northern Ireland were surveyed by questionnaire and participant observation. It was found that psychodrama was perceived as being useful by the four subjects who had a better education and were demonstrably more verbally expressive and extroverted. Alcohol problems need to be understood and treated in the social context in which they develop and thrive; psychodrama enpowers problem drinkers to explore their unique social context. PMID- 1625761 TI - The efficacy of primary nursing as a foundation for patient advocacy. AB - Modern nursing practice aims at addressing the needs of the client in a way which is consistent with his or her individual views, rights and wishes. Salvage (1) describes these changes in nursing as the advent of 'new nursing.' This has encouraged an interest in the concept of patient advocacy. This article examines the areas of practice which, it is suggested, affect the way in which nurses can take on the role of patients' advocate, the different types of relationship which may be formed between nurses and patients, and the effect of individual nurse's personal values in influencing planning and implementation of care. It is suggested that the organisational mode of primary nursing offers nurses a means to fulfil the role of patients' advocate through its emphasis on the crucial importance of the nurse's responsibilities and relationships with patients. PMID- 1625763 TI - The integration of a database and a statistical program in the analysis of a large scale survey in nursing. AB - Large scale surveys have conventionally been analysed using a statistical package. This saves considerable time and permits many more analyses to be undertaken than with more traditional methods. It does, however, have certain drawbacks. First, it does not help with the problem of data management. SPSS and Epfino, for example, have some facilities for data entry restrictions and cross checking. They are excellent for the static purpose for which they are designed, but rather crude in comparison with those provided by a dedicated database tool. Second, it requires considerable experience to achieve maximum benefit. Third, it does not help at all in the major undertaking of data exploration. The authors have analysed a large scale survey using a statistical package and a database in collaboration. Their experience is reported here. PMID- 1625762 TI - Private patients' perceptions of nursing practice in the National Health Service. AB - A study of private patients (n = 649) was carried out in Wessex Region in January 1991 to discover why patients decide to go private rather than use the NHS for in patient treatment. Relatively few patients complained of the attitudes of nurses in the NHS, but just over one third mentioned nursing as a significant problem in the NHS and, of this group, over half were critical of nurses' attitudes. Further analysis revealed that these perceptions were not based on direct experience (of those who said that nursing was a problem, only 5 per cent had been NHS in patients since 1985), but alarm about the public image of nursing remains. PMID- 1625764 TI - Visually impaired patients' perceptions of their needs in hospital. AB - This article reports on a study of visually impaired patients' perceptions of their social and psychological needs in hospital. A qualitative approach was taken to explore and describe these perceptions, and 18 in-patients from one ophthalmic hospital took part in semi-structured interviews lasting approximately half an hour. Patients did not agree on their most important need. Many stresses and methods of coping were specific to individual patients. Patients reported on three areas in which most of them had problems: behavior of some staff, anxiety, and communication, but most felt their physical needs were met by nurses. Implications and recommendations for nursing practice are discussed. In particular, the results indicate a need for individualised care. It is also apparent that further research is needed to explore nurses' beliefs and feelings towards visual impairment. PMID- 1625765 TI - Deterioration of spatial and nonspatial reference and working memory in aged rats: protective effect of life-long calorie restriction. AB - Two different aspects of learning (spatial and nonspatial) and two different types of memory (reference and working) were simultaneously measured in populations of 3- (young), 11- (adult), and 25-month-old (aged) rats fed ad libitum either a standard (ST) or a hypocaloric (HY) diet. All groups, regardless of age or diet, showed ability in learning all four versions of the task. However, old ST rats were significantly slower and less efficient at learning than the young and adult ST rats. In contrast, senescent HY rats' cognitive abilities did not differ from those of their young and adult counterparts. The decline in reference and working memory in the aged ST rats was more pronounced in the spatial than the nonspatial version of the task. This study confirms and extends to more specific aspects of memory our earlier finding that age-related cognitive deterioration in rats was antagonized by life-long calorie restriction. PMID- 1625766 TI - Regional synaptic pathology in Alzheimer's disease. AB - Synaptic pathology in Alzheimer's disease (AD) may occur diffusely or may have regional predilections. A new antibody called EP10 which detects synaptophysin like immunoreactivity was used to study synapses in postmortem brain tissue. Four brain regions from cases of AD and controls were studied. Controls with a wide range of ages were used to investigate the possibility of age-related changes in synaptophysin-like immunoreactivity. A significant reduction in the EP10 antigen was observed to occur with age in the control caudate but not in the hippocampus or temporal or occipital cortices. Antigen levels were significantly reduced in the hippocampus (77%) and the temporal cortex (54%) in AD. The expected abnormal pallor of the outer two-thirds of the dentate gyrus molecular layer was observed with immunocytochemistry. In the temporal cortex, the reduction in synaptophysin like immunoreactivity was inversely correlated with the neurofibrillary tangle count. No such relationship existed in the hippocampus. These results suggest that at least certain components of the synaptic loss in AD occur regionally and are disproportionately large in the hippocampus. PMID- 1625767 TI - Preservation of the density of the dopamine uptake complex in aging Fischer 344 rat brain. AB - This study was performed to determine if there are selective regional or global changes in the density or pharmacology of the dopamine uptake complex (DAUC) in aged rodent. Fifteen regions of the Fischer 344 rat (aged 4, 12, and 24 months) central nervous system were analyzed for the density of the DAUC employing [3H]GBR 12935 and in vitro quantitative autoradiography. Additionally, cocaine competitions were performed in the striatum of all of the animals. A 26-fold variation in the DAUC density was found in the regions sampled. However, no significant age-related changes were identified. Intrastriatal analysis of the DAUC density revealed binding heterogeneities; decreasing lateral to medial and decreasing dorsal to ventral gradients. No significant effect of aging on striatal gradients was observed. The proportion of high and low affinity sites for cocaine was unchanged in the three age groups. Taken together, these findings suggest a stability of this dopamine presynaptic marker in aging rat central nervous system. PMID- 1625768 TI - Convergent cholinergic activities in aging and Alzheimer's disease. AB - Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities have been examined postmortem in a series of 66 individuals with no evidence of CNS disease, ranging in age from 24 gestational weeks to 95 years and in 33 cases of Alzheimer's disease (AD) aged 57-89 years. In the normal human hippocampus a striking and highly significant age-related decline in ChAT occurred from middle to old age (between 40 and 100 years); a trend apparent at a later stage and to a lesser extent in the hippocampal gyrus. In both areas enzyme activity in AD was inversely related to age at death; reductions compared with the normal were on average 70-80% in the 60-70 year old groups compared with 30-40% in the 80-90 year old group. A similar trend was apparent with respect to acetylcholinesterase (AchE) histochemical activity associated with fibers and terminals (predominantly cholinergic and concentrated in CA3 and 4 of the hippocampus) but not with reactive perikarya (considered to be noncholinergic) present in both hippocampus and cortex. These data indicate that the normal aging human hippocampus may constitute a useful model for investigating the dysfunction or degeneration of basal forebrain cholinergic neurons in AD. PMID- 1625769 TI - Glucose enhancement of memory in elderly humans: an inverted-U dose-response curve. AB - In animals, enhancement of memory with glucose and many other treatments is characterized by an inverted-U dose-response curve. The present experiment examined the dose-response curve for glucose enhancement of memory in elderly humans. Using a repeated measures, counterbalanced, crossover design, the subjects (60-82 year olds) were tested on four sessions, separated by 1 week or more, for performance on the Wechsler Logical Memory Test after ingestion of a fruit drink sweetened with glucose (0, 10, 25, and 50 g) and saccharin matched to comparable taste. The findings indicate that glucose enhanced performance on this test in an inverted-U dose-response manner, with optimal enhancement obtained at the 25 g glucose dose. These findings provide further demonstration of glucose enhancement of memory in elderly humans and also describe an additional analogy between the characteristics of glucose enhancement of memory in animals and humans. PMID- 1625770 TI - Alzheimer's disease and aging: effects on perforant pathway perikarya and synapses. AB - The hippocampal perforant pathway originates in the entorhinal cortex (ERC) and terminates in the outer molecular layer of the dentate gyrus (DG). To compare the effects of normal aging and Alzheimer's disease (AD) on the elements of the perforant pathway, we compared relative perikaryal numbers (determined by counting cell bodies and estimating volumes) in layer II of the ERC with synaptic quantities (estimated from immunoreactivity for the synaptic terminal protein synapsin I and DG volume) in the molecular layer of the DG. The brains of 5 young and 9 elderly cognitively normal individuals, and of 9 AD patients were studied. In normal aging we found a significant age-related decline in perikaryal numbers in the ERC without demonstrable synaptic loss in the DG. In AD there was marked and equivalent, (or proportional) reduction in both ERC perikaryal numbers and DG synapses. These data suggest that in normal aging remaining neurons may continue to support a full array of synapses, perhaps due to mechanisms such as axonal sprouting, synaptic enlargement, or synaptic ingrowth. In AD, however, the accelerated neuronal loss may overwhelm such compensatory mechanisms or alternatively, independent synaptic and perikaryal losses may occur. PMID- 1625771 TI - Evidence for changes in the Alzheimer's disease brain cortical membrane structure mediated by cholesterol. AB - Small angle X-ray diffraction analysis of Alzheimer's disease (AD) lipid membranes extracted from cortical gray matter showed significant, reproducible structure changes relative to age-matched control samples. Specifically, there was an average 4 A reduction in the lipid bilayer width and significant changes in the membrane electron density profiles of AD cortical samples. There were no significant structure differences in the membrane bilayers isolated from an unaffected region (cerebellum) of the AD brain. Lipid and protein analysis of 6 AD and 6 age-matched controls showed that the phospholipid:protein mass ratio was unchanged but that the unesterified cholesterol:phospholipid (C:PL) mole ratio decreased by 30% in the AD temporal gyrus relative to age-matched controls. By contrast, the C:PL mole ratio in the cerebellum did not change significantly. X ray diffraction analysis of a cholesterol enriched AD sample demonstrated a virtual restoration of the normal membrane bilayer width and electron density profile, suggesting that the cholesterol deficit played a major role in the AD lipid membrane structure perturbation. Alterations in the composition and structure of the membrane bilayer may play an important role in the pathophysiology of AD by altering the activity and catabolism of membrane-bound proteins, including the beta-amyloid precursor protein. PMID- 1625772 TI - Detection of distinct isoform patterns of the beta-amyloid precursor protein in human platelets and lymphocytes. AB - Cerebral deposition of the amyloid beta-protein (A beta P), approximately 40 residue fragment of the integral membrane protein, beta-amyloid precursor protein (beta APP), has been implicated as the probable cause of some cases of familial Alzheimer's disease (AD). The parallels between A beta P deposition in AD and the deposition of certain plasma proteins in systemic amyloid diseases has heightened interest in the analysis of beta APP in circulating cells and plasma. Here, we describe distinct isoform patterns of beta APP in peripheral platelets and lymphocytes. PCR-mediated amplification of mRNA from purified platelets demonstrated the expression of all three major beta APP transcripts (beta APP770,751,695). The full-length, approximately 140 kDa form of beta APP751,770 was detected in membranes of resting and activated platelets but very little immature, approximately 122 kDa beta APP751,770 was found, suggesting a different processing of beta APP in platelets than that described in a variety of cultured cells and tissues. Platelets stimulated with thrombin, calcium ionophore, or collagen released the soluble, carboxyl-truncated form of beta APP (protease nexin-II), but no evidence for the shedding of full-length beta APP associated with platelet microparticles was found, in contrast to previous reports. As a positive control marker for microparticles, the fibrinogen receptor subunit, GPIIIa, was readily detected in platelet releasates. Resting and activated platelets contained similar amounts of the approximately 10 kDa carboxyl terminal beta APP fragment that is retained in platelet membranes following the constitutive cleavage of protease nexin-II. Nonstimulated peripheral B and T lymphocytes contained small amounts of membrane-associated mature and immature beta APP751,770. The potentially amyloidogenic full-length beta APP molecules present in circulating platelets and lymphocytes but not in microparticles could serve as a source of the microvascular A beta P deposited during aging and particularly in AD. PMID- 1625773 TI - In vitro and in vivo ethanolamine metabolism in rat brain: effect of time and aging. AB - The effect of the time in culture of foetal rat neurons and age on the incorporation of radioactive ethanolamine into methylated derivatives was investigated. Decreased incorporation of [3H]ethanolamine into its various methylated water-soluble and lipidic derivatives was observed in rat neurons cultures at 12 day in vitro (DIV) as compared to the 3rd and the 7th DIV. In vivo studies showed that there was a diminished labeling of methylated products in the older animals as compared to the younger ones. These in vitro and in vivo observations suggest a generalized decrease of N-methyltransferase activities during maturation and aging. PMID- 1625774 TI - Cholinergic fiber aberrations in nucleus basalis lesioned rat and Alzheimer's disease. AB - Innervation density and morphological aberrations of cholinergic fibers were studied with choline acetyltransferase (ChAT) immunocytochemistry and acetylcholinesterase (AChE) histochemistry in 30-35 month-old aged rats and rats with long-term bilateral lesions of the magnocellular basal nucleus (MBN). In addition, AChE histochemistry was performed on human cortical sections derived from autopsy brains of normal aged and Alzheimer's disease (AD) patients. A limited but variable number of morphological alterations were observed in ChAT immunoreactive fibers in the cortex and the hippocampus of the aged control rats. The aged MBN-lesioned rats displayed a severely reduced number of cholinergic fibers in the denervated areas of the neocortex, whereas the surviving fibers showed a strongly increased number of aberrations. Fiber anomalies were also observed in the cortex of the aged human subjects and Alzheimer patients, the latter showing a higher incidence of such aberrations. Only a part of these distended profiles were seen in close association with senile plaques as detected in the AChE-stained material. These findings suggest that experimental MBN lesions combined with aging share with AD the induction of large quantities of fiber malformations. Implications of possible mechanisms in both conditions are discussed. PMID- 1625775 TI - Familial Alzheimer's mutation: mRNA secondary structure revisited. AB - It has been suggested that the mutation at position 717 of the amyloid precursor protein (APP), found in several cases of familial Alzheimer's disease, affects the secondary structure of the corresponding messenger RNA and the rate of its translation (10). Phylogenetic analysis based on comparison with other mammalian APP sequences does not support this possibility. PMID- 1625776 TI - Quantitative electroencephalography in Parkinson's disease, dementia, depression and normal aging. AB - The relationship between depression and dementia in Parkinson's disease (PD) has rarely been explored. Using a quantitative EEG (qEEG) parameter, we studied four groups of subjects: PD, demented Alzheimer's type and major depressed patients and normal controls. The qEEG data were compared with those of the Mini-Mental State and the Hamilton Depression Scale. The qEEG pattern was different in the four groups of subjects. Moreover, there was a significant correlation between the qEEG data and the other variables, and, particularly, with the cognitive performances. Our findings demonstrate that the qEEG method of assessment may give valuable data for a better classification of dementia syndromes and for a distinction between dementia and pseudodementia. PMID- 1625777 TI - Neuroendocrine responses to a glucose challenge in substance users with high and low levels of aggression, impulsivity, and antisocial personality. AB - Plasma glucose concentrations, and plasma prolactin and cortisol responses to a 5 hour oral glucose tolerance test (OGTT) in 37 substance abusers, were examined to assess the relationship between varying degrees of antisocial personality, impulsivity, and aggressiveness and measures of endocrine function. Childhood and presenting aggression, impulsivity and antisocial personality features were evaluated by several self-report questionnaires. Those with high scores for psychopathic deviance (MMPI) differed in glucose levels following OGTT from those with low scores. Lower cortisol nadir levels were associated with higher scores on measures of antisocial personality and aggressiveness. Also, prolactin response to glucose was attenuated relative to baseline levels in the more antisocial and aggressive subjects. The results indicate that substance abusers with high levels of self-reported antisocial personality and aggressive behavior have altered neuroendocrine responses to glucose challenge, although there was no evidence of hypoglycemia. No one personality or behavioral trait, as measured by our test battery, more strongly predicted neuroendocrine responses to glucose administration. Thus, our data partially support other reports of altered neuroendocrine responses to stressful challenges in aggressive/antisocial individuals. PMID- 1625778 TI - Saliva cortisol responses to unpleasant film stimuli differ between high and low trait anxious subjects. AB - The present study, which aims to investigate effects of low and high trait anxiety on saliva cortisol secretion, was performed on 64 healthy male volunteers. They were assigned either to an unpleasant or a control film. Furthermore, subjects were divided within each film group by median split of their anxiety ratings into high and low trait anxious groups, resulting in four equal-sized groups. Saliva cortisol and mood ratings were the dependent variables. In contrast to the low anxious, the high anxious subjects responded with a diminished saliva cortisol response. PMID- 1625779 TI - Attenuated late positivity in the visual evoked potential in aphasia induced by lesions in anterior speech area. AB - Seven anterior aphasics, 7 nonbrain-damaged subjects and 7 normal controls were tested for their visual evoked potentials. Aphasics showed an attenuation of the long latency positivity related to interest in the stimulus. The attenuation may indicate the subject's failure to signal communicative intention. Thus the attenuated positivity may be a physiological correlate of a behavioral state (aphasia) induced by brain lesions. PMID- 1625780 TI - Serotonergic inhibition of limbic and thalamic seizures in cats. AB - To clarify the role of the serotonergic system in limbic and thalamic epileptic activity, we examined the effects of 5-hydroxytryptophan (5-HTP, 20 and 40 mg/kg) on fully kindled seizures from the hippocampus and lateral geniculate nucleus. The intraperitoneal administration of 20 mg/kg 5-HTP exerted no anticonvulsant effect on hippocampal kindled seizures, and a higher dose (40 mg/kg) produced a significant reduction in the behavioral seizure stage. 5-HTP at 20 mg/kg displayed no suppressive effect on lateral geniculate seizures, and 5-HTP at 40 mg/kg significantly reduced both the seizure stage and afterdischarge duration. Our data suggest that serotonergic mechanisms play an inhibitory role in seizures kindled from these brain regions. PMID- 1625781 TI - Leftward shift of R-axis on electrocardiogram in patients with panic disorder and depression. AB - In a prospective study, we have compared R-axis on routine electrocardiograms of panic disorder patients (n = 52) with that of depressed patients (n = 41) and normal controls (n = 65). All subjects were physically healthy and were normotensive. There was a significant leftward shift of R-axis in both depressed and panic disorder patients compared to normal controls. The implications of these findings are discussed. PMID- 1625782 TI - Lymphocyte subsets in major depressive patients. Influence of anxiety and corticoadrenal overdrive. AB - We studied 26 inpatients (17 females; mean age +/- SD: 41.2 +/- 14.3 years) who met the DSM III criteria for a major depressive episode and had a mean (+/- SD) Hamilton Depression Score of 19.3 +/- 8.0. All patients were drug free and medically healthy at the time of experimentation. We found a significant correlation between the CD4/CD8 ratio and the Hamilton Anxiety Score (r = 0.57, p less than 0.005). When splitting our sample in dexamethasone suppression test suppressors (DST-S) and nonsuppressors (DST-NS), this relationship appeared only in DST-NS (DST-NS: r = 0.81, p less than 0.005; DST-S: r = 0.20, p = NS). These results are discussed in terms of heterogeneity among major depressive disorders and possible relationships between catecholaminergic activity and the immune system. PMID- 1625784 TI - Brain Research Association, 9th National Meeting. Nottingham, U.K., 6-8 April 1992. Abstracts. PMID- 1625783 TI - Abnormal electroretinography in schizophrenic patients with a history of sun gazing. AB - Electroretinographic (ERG) measurements were performed in 9 schizophrenic patients and in 13 control subjects. The measurements of schizophrenic patients as a group did not differ from those of normals. However, 6 schizophrenic patients who had a past history of sun gazing showed a decrease in retinal responsiveness under conditions of light adaptation. These results suggest that a subgroup of schizophrenic patients, who show deviant light-related behavior, have abnormal ERG. We postulate that an abnormality in retinal dopaminergic neurons, which are known to reduce light responsiveness of horizontal and ganglion cells, is the underlying pathophysiology of this clinical finding. PMID- 1625785 TI - Evidence that 3 alpha-hydroxy-5 alpha-pregnan-20-one is the metabolite responsible for anesthesia induced by 5 alpha-pregnanedione in the mouse. AB - Mice were anesthetized with [3H]5 alpha-pregnanedione (5 alpha). Brain levels for 5 alpha and its metabolites were quantitated and compared at time points following injection and at two behavioral endpoints that are characteristic of the anesthetized state. The results support the hypothesis that 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha), a metabolite of 5 alpha, mediates this anesthetic response, and they weigh against the hypothesis that 5 alpha itself is solely responsible for activity. Anesthesia occurred at 3-8 min following injection. During this period, levels of 3 alpha derived from 5 alpha were comparable to those seen when 3 alpha was administered alone. It is estimated that 5 alpha, if active at all, is at least 3-5 times less potent than 3 alpha. PMID- 1625786 TI - Platelet secretory products have a damaging effect on neurons. AB - We studied the direct effect of platelet secretory products on rat spinal cord explants. Morphological changes in the ventral horn neurons were assessed after staining for acetylcholinesterase (AChE). Compared to control, exposure to platelet secretory products was associated with a significant decrease in the number of AChE-positive neurons per ventral horn. Aspirin appeared to partially prevent this neurotoxicity. These results suggest that platelet secretory products may contribute to neuronal injury. PMID- 1625787 TI - Apparent disappearance of postseizure inhibitions and intensity of seizures during the development of rapid kindling in rabbits. AB - The evolution of seizures and postseizure inhibitions in the course of 'rapid kindling' and after the termination of stimulation were studied in rabbits with chronically implanted electrodes (neocortex, dorsal hippocampus, amygdala, caudate nucleus). The amygdala (n = 4) or hippocampus (n = 7) was electrically stimulated every 5 min. Generalized convulsions and wide-spread electrographic epileptic changes together with a striking shortening of postictal refractory periods were produced by this procedure within 2-6 h. In most cases, these epileptogenic effects continued their progression after the termination of stimulation for more than 2-4 weeks. The degree of reduction of postseizure inhibition durations was significantly greater than the degree of increase of generalized motor seizure durations. These may be mediated by mechanisms which facilitate the onset of seizure but do not significantly influence seizure expression. PMID- 1625788 TI - Prolonged postischemic hyperventilation reduces acute neuronal damage after 15 min of cardiac arrest in the dog. AB - Hyperventilation is commonly used as a constituent of antiedematous therapy after global cerebral ischemia. The effect of hyperventilation on brain functions, however, is complex, and a number of mechanisms involved remains unclear. In this study, we attempted to determine whether postischemic hyperventilation influences acute neuronal changes developing during recirculation. Two groups of dogs underwent 15 min of cardiac arrest and cardiopulmonary resuscitation with an 8 h survival. After resuscitation, in group A the internal environment was maintained in the physiological ranges. In group B the animals were artificially hyperventilated maintaining a high level of respiratory alkalosis during recirculation. Histopathological examination of the vulnerable structures was performed using the Nauta degenerating method and the argyrophilic neurons were counted. Statistically significant amelioration in group B suggests that postischemic hyperventilation may act as a neuroprotective factor. PMID- 1625789 TI - Subcellular localization of insulin-like growth factor I (IGF-I) in Purkinje cells of the adult rat: an immunocytochemical study. AB - Insulin-like growth factor I (IFG-I) was localized by light and electron microscopic immunocytochemistry in the adult rat cerebellum. Neurons showing the same cytological characteristics and pattern of synaptic input as Purkinje cells were IGF-I immunoreactive. In these neurons, intense electron-dense reaction product was consistently located in the rough endoplasmic reticulum and, occasionally, in multivesicular bodies and associated with the nuclear envelope. Thus, the results of this study suggest synthesis IGF-I in Purkinje cells and furthermore provide anatomical support for IGF-I participation in paracrine or autocrine regulatory systems in the brain. PMID- 1625790 TI - The changes in the activity of pudendal motoneurons in relation to reflex micturition evoked in decerebrate cats. AB - Reflex micturition was evoked in both non-immobilized (n = 5) and immobilized (n = 5) decerebrate cats by filling the bladder with physiological saline. Intracellular recordings were made from pudendal motoneurons (PU-MNs; n = 14) throughout the periods of before, during and after reflex micturition. The changes in the activity of PU-MNs were correlated with those in the intravesical pressure. Our results support the proposition that coordination of the sphincters and the detrusors is established by a gating mechanism, which is activated by the supraspinal source such as the pontine micturition center. PMID- 1625791 TI - Direct projections from the globus pallidus to the midbrain and pons in the cat. AB - Employing the anterograde and retrograde axonal tracing techniques with Phaseolus vulgaris leucoagglutinin and cholera toxin B subunit, we demonstrated direct projections from the globus pallidus (GP) to the midbrain and pons in the cat. Cells of origin of these projections were localized in the caudal 2/3 of the GP, and their major target sites included the peripeduncular region, nucleus of the brachium of the inferior colliculus, para-lateral lemniscal zone, nucleus sagulum, external and pericentral nuclei of the inferior colliculus, and cuneiform nucleus. A combination of retrograde axonal tracing and immunohistochemistry for choline acetyltransferase revealed that GP neurons giving rise to such descending projections were primarily non-cholinergic. PMID- 1625792 TI - Changes in extracellular concentration of amino acids in the hippocampus during cerebral ischemia in stroke-prone SHR, stroke-resistant SHR and normotensive rats. AB - To investigate the role of glutamate release in cerebral ischemia, the amounts of amino acids (glutamate, taurine, alanine, glycine and glutamine) released in the hippocampal CA1 region of stroke-prone SHR (SHRSP), stroke-resistant SHR (SHRSR) and normotensive rats (WKY) were determined during and after cerebral ischemia by the microdialysis method under halothane anesthesia. Cerebral ischemia was produced by the occlusion of both common carotid arteries for 20 min. The basal amino acids release did not differ among the three strains of rats, but ischemic glutamate and taurine releases were more marked in SHRSP than in other strains. These results suggest that the massive glutamate release during cerebral ischemia of SHRSP might be related with severe neuronal cell injury. PMID- 1625793 TI - Brain amines in glucocorticoid-induced hypertension in the rat. AB - A two week administration of the glucocorticoid betametasone to male Wistar rats produced a mild hypertensive state. The brain of these rats showed some significant changes in amine and metabolite content with respect to normotensive controls. Epinephrine and metanephrine were increased in the rostral ventrolateral medulla and in the preoptic area. Epinephrine also increased in the septal area. Normetanephrine decreased in the rostral ventrolateral medulla. Dopamine and homovanillic acid increased in septal and preoptic areas. Dopamine alone increased in rostral ventrolateral medulla. Serotonin and 5-hydroxyindole-3 acetic acid increased in the septal area and dorsal medulla. These changes suggest significant alterations in the aminergic activity of the brain circuitry known to regulate cardiovascular functions; the changes may play a basic role in the development and maintenance of glucocorticoid-induced hypertension. PMID- 1625794 TI - The cholinergic system participates in thyrotropin-releasing hormone (TRH) regulation. AB - The effect of chronic atropine treatment was studied on thyrotropin releasing hormone (TRH) content of several brain areas in Wistar rats. Atropine produced TRH increases in the septal area, preoptic area and the hypophysis; this was observed when rats were killed immediately after the last dose, while a decrease was observed only in the hypophysis 48 h after the last atropine dose. TRH concentration in cerebrospinal fluid rose significantly after atropine withdrawal with respect to controls. Treatment with eserine, an acetylcholinesterase inhibitor, produced the same effect. These results indicate cholinergic participation in central TRH regulation. PMID- 1625795 TI - Variations in cerebellar morphology of the Atlantic stingray, Dasyatis sabina. AB - The cerebellar corpus of the Atlantic stingray consists of an anterior lobe which is divided into rostral and caudal lobules, and a posterior lobe. The long axis of the posterior lobe and rostral lobule of the anterior lobe both lie along the midline, whereas the orientation of the caudal lobule varies. We examined this variation in 127 animals. In 52% the long axis of the caudal lobule lay on the right of the midline, in 21% it was on the left, and in 27% across the midline. While this distribution is not random, it is not related to size or sex. It is proposed that the observed variation is the reflection of variation in the cerebellar developmental program. PMID- 1625796 TI - Luteinizing hormone-releasing hormone in the pigeon terminal nerve and olfactory bulb. AB - The presence of a terminal nerve in the avian brain has recently been reported. As the terminal nerve in other classes of vertebrates contains luteinizing hormone-releasing hormone (LHRH), we used immunocytochemistry to determine whether the pigeon terminal nerve also contained LHRH. We found LHRH immunoreactivity in the olfactory nerve and in the olfactory bulb. The distribution of LHRH neurons was similar to the LHRH neuronal migration pathway during development. PMID- 1625797 TI - Early effects of unilateral lesions of substantia nigra on immune reactivity. AB - It has recently been demonstrated that central dopaminergic pathways are asymmetrically involved in the modulation of the immune response. Mitogen-induced proliferation of T lymphocytes was shown to be enhanced 4-6 weeks after right lesion of the substantia nigra (SN) in mice, when compared to left lesioned and control animals. In order to study the involvement of post lesion neuronal reorganization in these results, the same immunological parameters were determined as early as 2 weeks after right or left lesion of the SN. We showed that the lymphoproliferation induced by alpha CD3 and concanavalin A was decreased in both lesioned groups, but phytohemagglutinin-induced mitogenesis was more impaired in the right than in the left lesioned animals. Hence, the time course effects of the right lesions of SN shifted from depression to enhancement of the T lymphocyte responsiveness. This shift appeared to occur around the two weeks period following the lesion. These immunomodulatory effects of unilateral SN lesioning, which depended on time and side of lesion, were similar to those observed after hemidecortication. Based on these findings, it is reasonable to suggest that asymmetry in brain immunomodulation involves functionally related dopaminergic and cortical networks. PMID- 1625798 TI - Nerve growth factor induces proliferation and enhances fiber regeneration in oligodendrocytes isolated from adult pig brain. AB - Mature oligodendrocytes (OL) isolated from adult pig brains start to regenerate their fibers after 4-5 days in vitro (DIV); after 14 DIV a network of OL fibers is formed. Growth factors, of which it was known that they play an important part during proliferation and differentiation of OL progenitor cells, were used to study their influence on the regeneration of mature OL. For this purpose, OL were treated at 6 DIV with different concentrations of various growth factors. At 24 h intervals the [3H]thymidine incorporation was measured and at 8 DIV the OL fiber production evaluated. None of these factors did influence the regenerative process to any significant extent except nerve growth factor (NGF). For the first time it could be shown that NGF enhanced the OL fiber regeneration considerably and induced the proliferation of a subset of OL. These results may have important implications for the remyelinating process in demyelinating diseases such as multiple sclerosis. PMID- 1625799 TI - Nitric oxide inhibitors attenuate N-methyl-D-aspartate excitotoxicity in rat hippocampal slices. AB - To investigate whether nitric oxide (NO) plays a role in the neurotoxicity produced by N-methyl-D-aspartate (NMDA) we have examined the effects of NO inhibitors on NMDA-mediated neurodegeneration in the CA1 region of rat hippocampal slices. L-NG-Monomethylarginine, L-NG-nitroarginine and hemoglobin markedly diminished the toxicity produced by activation of NMDA receptors without interfering with NMDA receptor-mediated ion currents or synaptic responses. The neuroprotective effects are reversed by coapplication of L-arginine with the NO synthase inhibitors. These results suggest that activation of the NO system is an important component of the biochemical cascade leading to neurodegeneration produced by NMDA receptors. PMID- 1625800 TI - Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid. AB - Many biochemically diverse proteins can give rise to amyloid fibrils; however, they are all accompanied by P component and glucosaminoglycans. With antibodies specific to apolipoprotein E (apo E) we used immunohistochemical techniques to test for the presence of this protein in both cerebral and systemic amyloid. We found apo E immunoreactivity in all tested types of cerebral and systemic amyloid. In amyloid deposits apo E P, component and glucosaminoglycans may be acting as 'pathological molecular chaperones'. The latter we define as a group of unrelated proteins that induce beta-pleated conformation in amyloidogenic polypeptides. PMID- 1625801 TI - Immunocytochemical localization of beta thyroid receptor in the rat cerebellum. AB - Using a specific antibody, we report here the immunocytochemical localization of the beta thyroid receptor (TR beta) in the adult rat cerebellum. We show that the immunoreactivity is specifically located in the Purkinje cells while the internal granular layer and the molecular layer are devoid of staining. In Purkinje cells, the immunoreactivity is either limited in the nuclei, or predominantly located in the perinuclear region and the cytoplasm. The presence of thyroid receptor is correlated with the presence of TR beta mRNAs as determined by Northern analysis. PMID- 1625802 TI - Mechanism of rapid K(+)-induced swelling of mouse astrocytes. AB - Cultured astrocytes from newborn mouse cortex were impaled with double-barrelled ion-sensitive microelectrodes to investigate their response following a 5 min exposure period to saline containing 60 mM K+. The membrane potential decreased from -74 to -11 mV, the intracellular K+ concentration increased from 102 to 145 mM and the intracellular pH increased from 7.05 to 7.60 indicating an increase in the HCO3- concentration from 9 to 31 mM. All changes were reversible. In additional series of experiments the cells were loaded with choline and the application of a bias current to electrodes containing the Corning 477317 resin made them more sensitive to choline than to K+. This resulted in a decrease of the ion potential during K+ exposure, which stabilized within 2 min. It is assumed that this is due to a dilution of intracellular choline by water intake. Thus, the early K(+)-evoked swelling response can be explained by a fast (approx. 2 min) swelling induced by K+ and HCO3- (and Cl-) influx. PMID- 1625803 TI - Role of Ia muscle spindle afferents in post-contraction and post-vibration motor effect genesis. AB - Experiments carried out on 14 human subjects showed that long-lasting involuntary tonic motor responses occurred after the offset of muscle vibration (70 Hz, 0.5 mm, duration 30 s). These post-vibratory biceps and triceps brachii motor responses were compared with the motor responses observed in the same subjects after performing an isometric contraction of the same duration, i.e., post contraction responses, or the so-called 'Kohnstamm phenomenon'. The results show the existence of close similarities between these two types of motor after effect, particularly as regards the muscle sites where they develop, their amplitudes and their temporal patterns (latencies and offset times). Neither type of excitatory post-effect can be elicited by co-contracting or co-stimulating two antagonist muscles at the same frequency. Lastly, visual stimulation can cause both types of motor response to switch from one muscle to its antagonist. Comparative analysis of the spindle proprioceptive activities recorded in response to either vibration or isometric contractions suggests that these motor after-effects may both result from the fact that the spindle afferents from agonist and antagonist muscles are asymmetrically activated in these two particular situations. PMID- 1625804 TI - Chronic infusion of nerve growth factor does not rescue pyramidal cells after transient forebrain ischemia in the rat. AB - Male Wistar rats received chronic intracerebroventricular infusions of nerve growth factor (NGF) starting immediately before induction of a transient forebrain ischemia and continuing until 7 days after the infarct. Ischemia was induced by carotid occlusion and simultaneous hypotension. Seven days after the infarct the brains were examined histologically and the number of necrotic cells in the hippocampus were counted. The results did not reveal any difference in treated vs. untreated animals. The data suggest that application of exogenous NGF does not prevent ischemic cell death in the hippocampus. PMID- 1625805 TI - Block of synapse formation between cerebral cortical neurons by a protein kinase inhibitor. AB - Synchronized Ca2+ transients in cultured hippocampal neurons reflect the pattern of underlying electrical activity. Here we demonstrate a similar synchronization of cerebral cortical neurons in culture, and show that this functional coupling is correlated to the appearance of morphologically identified synapses using electron microscopy. During screening of a series of drugs for inhibition of in vitro synaptogenesis, the continuous presence of a protein kinase inhibitor (K 252b) in the culture medium was found to block the synchronous firing and to decrease significantly the number of morphologically identifiable synapses. Since K-252b does not permeate the cell membrane, the results strongly suggest that phosphorylation of cell surface protein(s) by a K-252b sensitive-protein kinase is an essential process in synapse formation. PMID- 1625806 TI - Ethanol inhibits excitotoxicity in cerebral cortical cultures. AB - Excitatory amino acid neurotransmitters have been implicated in the pathogenesis of cerebral ischemia and related forms of acute neuronal injury. Because ethanol inhibits cellular signaling mechanisms activated by excitatory amino acids, we examined its effect on excitatory amino acid-induced toxicity in neuron-enriched cultures prepared from rat cerebral cortex. Both glutamate and N-methyl-D aspartate (NMDA) were toxic to cultured cortical cells, as demonstrated by a reduction in their ability to exclude trypan blue dye, and this toxicity was reversed by the NMDA antagonist MK-801. Ethanol (100 mM) provided partial protection from the excitotoxic effect of NMDA. Thus ethanol, like conventional excitatory amino acid antagonists, can attenuate excitotoxic neuronal injury in vitro. PMID- 1625807 TI - Widespread neuronal degeneration after ibotenic acid lesioning of cholinergic neurons in the nucleus basalis revealed by in situ hybridization. AB - In efforts to test the cholinergic hypothesis for Alzheimer's disease and to create an animal model for this disease, ibotenic acid has been used to lesion cholinergic neurons in the basal forebrain. In this study we have used in situ hybridization with oligonucleotide probes specific for mRNAs encoding choline acetyltransferase and glutamic acid decarboxylase, respectively, to study the effects of such a lesion. Our results show that lesion paradigms normally used to induce neuronal degeneration in nucleus basalis by ibotenic acid not only lesion the cholinergic neurons within this nucleus, but in addition, a major fraction of gamma-aminobutyric acid (GABA) neurons in nucleus basalis, substantia innominata, globus pallidus and ventral pallidum. PMID- 1625808 TI - Enhancement of NMDA-evoked neuronal activity by glycine in the rat spinal cord in vivo. AB - The effects of iontophoretically administered N-methyl-D-aspartate (NMDA), glycine and strychnine on nociceptive dorsal horn neurons of the rat spinal cord were studied to test the hypothesis that their responses to NMDA are influenced in vivo by glycine acting at a strychnine-insensitive site. Experiments were carried out on 44 dorsal horn neurons responsive to microiontophoretic application of NMDA and peripheral stimulation. Glycine alone either enhanced or inhibited NMDA responses depending upon its dose (151% and 68% of control, respectively). Strychnine alone increased the NMDA-induced neural firing (129%), suggesting the presence of endogenous glycine. When glycine was co-ejected with strychnine, NMDA responses were further elevated (171%) revealing the activation of strychnine-insensitive binding sites. These data provide evidence that glycine can potentiate NMDA responses of nociceptive dorsal horn neurons in vivo and thus that glycine sites on NMDA receptors on these neurons are not saturated. PMID- 1625809 TI - Reduced urinary bladder afferent conduction velocities in streptozocin diabetic rats. AB - Previous experiments in our laboratory have described the method used to measure the conduction velocity distribution of a selected group of fibers (Brain Res., 520 (1990) 83-89). We have applied this technique to the 2 month streptozotocin diabetic rat. Glycosylated hemoglobin values measured at the time of death were 17.19 +/- 4.74% (diabetic, n = 8) and 4.07 +/- 0.74% (controls, n = 6). Diabetic bladders were thicker and heavier. The wet weights were 0.50 +/- 0.11 g (diabetic, n = 7) and 0.16 +/- 0.01 g (controls, n = 6). The conduction velocities of a total of 151 and 86 single afferent fibers were measured in the diabetic and control animals respectively. The conduction velocity distribution of the diabetics showed a shift towards slower speeds when compared to controls. The mean conduction velocities were 1.70 m/s for diabetics and 2.84 m/s for controls. The percent of units with conduction velocities greater than 2.5 m/s was 17.2 for diabetics and 36.0 for controls. This experiment demonstrates, for the first time, that diabetes causes a significant reduction of afferent conduction velocities in a functionally well-defined system. PMID- 1625810 TI - Localization of dystrophin in the Purkinje cells of normal mice. AB - A monoclonal antibody that reacts with a mid rod fragment of dystrophin was used to localize this protein in the central nervous system (CNS). Due to a low abundance of dystrophin in the CNS, an immunoperoxidase reaction amplified with a biotin-avidin system was used. All Purkinje cells in normal mice were dystrophin positive while the mdx mouse cerebellum was completely devoid of reaction. Dystrophin staining was present in the soma and dendrites of Purkinje cells but not in their axons. This uniform dystrophin labelling in the normal mouse Purkinje cells indicates that this protein is not only localized in synaptic contact regions of the CNS. PMID- 1625811 TI - Preprogastrin-releasing peptide messenger ribonucleic acid: neuroanatomical localization in rat brain by in situ hybridization with synthetic oligodeoxynucleotide probes. AB - Gastrin-releasing peptide (GRP) is a 27 amino acid peptide that is present in both the central and peripheral nervous systems and that shares immunological and functional properties with the amphibian peptide, bombesin. GRP has multiple putative biological functions including effects on feeding behaviour and carbohydrate metabolism, body temperature, and effects on hormone release, but little is known about the regulation of GRP gene expression in the brain. This study examined the distribution of neurones expressing preproGRP mRNA in rat brain by in situ hybridization of [35S]-labelled DNA oligonucleotides. PreproGRP mRNA was detected in several regions of brain, with highest concentrations in the parvocellular paraventricular and suprachiasmatic nuclei of the hypothalamus, the lateral and basolateral nuclei of the amygdala, the amygdaloid-hippocampal area and the ventral part of the granule cell layer of the dentate gyrus. Moderate levels were seen in layers II and III of the cingulate and retrosplenial cortex, the medial and mediobasal nuclei of the amygdala, the anteroventral thalamic nucleus; medial geniculate nucleus and the parabrachial nucleus. These findings are largely consistent with the cellular localization of GRP-like immunoreactivity in rat brain and recent studies of preproGRP mRNA localization using cRNA probes. The distribution of preproGRP mRNA observed further suggests the involvement of GRP in the central regulation of several functions including regulation of hypothalamic/pituitary hormone release. PMID- 1625812 TI - Locomotor rhythms induced by methylphenidate in suprachiasmatic nuclei-lesioned rats. AB - A robust locomotor activity rhythm with a circadian period appeared by chronic treatment with methylphenidate or methamphetamine in the suprachiasmatic nuclei (SCN)-lesioned rats whose circadian rhythms had been abolished. The appearance of the rhythmicity was accompanied by an increase in the activity level. However, significant circadian periods were detected only in rats whose locomotor activity increased more than 200% of the pretreatment levels. An increase in the activity level is necessary to generate and/or express the circadian locomotor rhythm in SCN-lesioned rats and there seems to be a threshold. PMID- 1625813 TI - Central respiratory neurons of the adult rat regrow axons preferentially into peripheral nerve autografts implanted within ventral rather than within dorsal parts of the medulla oblongata. AB - A great number of severed central nervous system (CNS) neurons of the adult rat have the capillary to regrow axons into peripheral nerve autografts. In the present experiment, autologous segments of the peroneal nerve were inserted perpendicularly to the dorsal surface of the medulla oblongata more or less laterally within either the ventral respiratory group or the so-called dorsal respiratory group (ventrolateral grafts, n = 5; dorsolateral grafts, n = 5). From 2 to 4.5 months after the graft implantation, spontaneous unitary activities (n = 197) were recorded within all the grafted nerves: they were found to arise from both central respiratory (R, n = 60) and non-respiratory (NR, n = 137) neurons which were giving off regenerated axons along the nerve grafts. The graft reinnervation by respiratory axons was found to be significantly more abundant within the medullary ventrolateral grafts than within the dorsolateral ones. The low rate of axonal regeneration from respiratory neurons observed within the dorsolateral grafts provides further evidence that the number of the respiratory neurons in the dorsal respiratory group, if present at all, is much smaller than that of the ventral respiratory group in the rat. PMID- 1625814 TI - Altered basal firing pattern and postactivation inhibition of locus coeruleus neurons in spontaneously hypertensive rats. AB - We compared the spontaneous unit activity and inhibition of impulse activity following antidromic activation (postactivation inhibition, PAI) of locus coeruleus (LC) neurons in spontaneously hypertensive rats (SHR) with those of LC neurons in Wistar-Kyoto rats (WKY). Spontaneous spikes of the LC were analyzed by interspike time histograms. The basal unit activity and variation coefficient of the interspike interval were decreased in SHR. The duration of the PAI which was yielded by antidromic activation from the dorsal noradrenergic bundle was shortened in SHR. These findings suggest that SHR LC neurons possess an altered basal firing pattern and inhibitory mechanism. PMID- 1625815 TI - Adenosine modulation of potassium currents in preganglionic nerve terminals of avian ciliary ganglia. AB - Potassium currents in calyciform nerve terminals of the avian ciliary ganglion were analyzed using a single microelectrode voltage clamp. The modulatory affects of adenosine on these currents was also determined. Intracellular CsCl (1 M) blocked the steady-state outward current, indicating that it is mostly carried by K+. Tetraethylammonium (TEA, 10 mM) blocked over 40% of the outward current at a command potential of -30 mV. If Ca2+ influx was blocked by CoCl2 (5 mM), the steady-state outward current was reduced by over 16% in the nerve terminals suggesting that about one fifth of the outward current passes through calcium activated potassium channels IK(Ca). Adenosine (50 mM) decreased the outward steady-state current over a wide range of command potentials in most terminals studied but failed to decrease this current in the presence of CoCl2 (5 mM). It is concluded that adenosine blocks IK(Ca) in nerve terminals. PMID- 1625816 TI - Controlled ultraviolet irradiation generates endothelial damage without affecting the nerve terminals of the cerebral artery in cats. AB - The vesicles of adventitial autonomic nerve terminals were examined quantitatively under an electron microscope in controlled ultraviolet ray (UV) irradiated cerebral vessels. Five cats whose basilar arteries were irradiated with UV (UV group) and 5 cats whose basilar arteries were irradiated with visible rays (control group) were compared. Endothelial vacuolation was observed only in the UV group. There was no statistically significant difference in the diameters of the dense-cored vesicles, related to noradrenaline, and clear vesicles, related to acetylcholine, between the two groups. It is concluded that controlled UV irradiation which generates endothelial damage does not affect the vascular adventitia ultrastructurally. PMID- 1625818 TI - Basic fibroblast growth factor (bFGF) acts centrally in the brain to inhibit gastric emptying in rats. AB - In the present study, we evaluated the central nervous system action of basic fibroblast growth factor (bFGF) on gastric emptying of a liquid meal in conscious rats using a Phenol red method. Intracisternal injection of bFGF dose-dependently inhibited gastric emptying, while intraperitoneal injection of bFGF at the same doses failed to alter gastric emptying. These results suggest for the first time that bFGF acts in the central nervous system to delay gastric emptying. PMID- 1625817 TI - Slowing of the dominant occipital rhythm in electroencephalogram is associated with low concentration of noradrenaline in the thalamus in patients with Alzheimer's disease. AB - The thalamus is involved in the regulation of the neocortical rhythmicity reflected in EEG as the alpha rhythm. Recent evidence suggests that the thalamus is affected in Alzheimer's disease (AD). We studied the relationship between the dominant occipital rhythm of the lifetime EEG and the choline acetyltransferase activity (ChAT) and monoamine concentrations in the postmortem thalamus of 20 histologically verified AD patients. The AD patients were divided into 3 groups (5-6 Hz, 7 Hz and 8-9 Hz) according to the frequency of the dominant occipital rhythm (FOC). Noradrenaline (NA) concentrations were significantly lower for the 5-6 Hz and 7 Hz subgroups as compared to the 8-9 Hz subgroup. The NA content of the thalamus correlated significantly with the FOC (r = 0.46, P = 0.04). The ChAT activity or concentrations of dopamine or serotonin did not correlate with the FOC or differ across the AD subgroups. The results suggests that the noradrenergic deficit of the thalamus may contribute to slowing of the dominant occipital rhythm in AD. PMID- 1625819 TI - Degeneration of motor nerve fibers enhances the expression of calcitonin gene related peptide in rat sensory neurons. AB - Calcitonin gene-related peptide (CGRP) in skeletal muscle is of neural origin. After degeneration of sensory fibers induced by removal of the lumbar dorsal root ganglia (DRG), the CGRP content in the rat soleus muscle was reduced to about 5% of the normal level. In contrast, degeneration of motor fibers induced by sectioning of the lumbar ventral roots markedly increased the CGRP content in the soleus muscle and CGRP levels in the lumbar DRG. It is suggested that the expression of CGRP in sensory neurons is up-regulated by some humoral factor induced by degeneration of motor nerve fibers. PMID- 1625820 TI - Nerve growth factor (NGF) in rat brain following long-term barbital treatment: relation to convulsions and cognitive function. AB - Nerve growth factor (NGF) protein has been implicated in alterations of cognitive function either following brain damage, selective lesions or aging. Groups of rats were given long-term (48 weeks) oral barbital treatment or tap water and following an extended period of abstinence (14 weeks) were tested for spatial learning ability in the Morris swim maze. Following the maze test, they were sacrificed and the NGF content of hippocampal and cortical brain regions were analyzed. Barbital treated rats were divided into convulsing and non-convulsing groups. It was found that there was a slight, significant increase (12%) in NGF content of the hippocampus in convulsing rats. Correlations between maze learning performance, brain weight and NGF in the cortex indicated a significant negative relationship between (a) performance and brain weight on day 1 of testing and (b) NGF content and performance on day 2. These data indicate some involvement of NGF in functions derived from a considerably different animal model to those applied previously. PMID- 1625822 TI - Possible functional consequences of synaptic reorganization in the dentate gyrus of kainate-treated rats. AB - The hypothesis that lesion-induced hippocampal granule cell axon sprouting causes granule cell hyperexcitability was tested in the rat. Kainic acid damaged dentate hilar neurons, decreased granule cell inhibition, and increased granule cell excitability to afferent stimulation, all before synaptic reorganization occurred. Granule cell recurrent inhibition and relatively normal excitability were unexpectedly restored as granule cell axon sprouting occurred. Anatomical analysis revealed that a dense innervation of inhibitory neurons by aberrant granule cell axons was a consistent feature in each animal. These results indicate that granule cell hyperexcitability precedes dentate synaptic reorganization and is associated with the selective interneuron loss that is the presumed stimulus for axon sprouting. Thus, if granule cell axon sprouting has functional significance, it may be primarily inhibitory, rather than epileptogenic, in nature. PMID- 1625821 TI - Effect of dietary n-3 fatty acid deficiency on blood-to-brain transfer of sucrose, alpha-aminoisobutyric acid and phenylalanine in the rat. AB - Possible alterations in blood-to-brain unidirectional transport of sucrose (mol. wt., 342), alpha-aminoisobutyric acid (mol. wt., 104), and L-phenylalanine (mol. wt., 165) induced by a diet deficient in n-3 polyunsaturated fatty acids were studied with respect to blood-brain barrier function. Two groups of rats were for to two generations with a semisynthetic diet. One group of rats was fed a peanut oil+rapeseed oil diet which contained both essential fatty acids: linoleic acid (18:2 n-6) and alpha-linolenic acid, (18:3 n-3). Another group was fed a diet of peanut oil, this diet (containing 18:2 n-6) was deficient in alpha-linolenic acid. The experiments were performed at 6 months of age. Unidirectional transfer rate constants (Ki) of sucrose, alpha-aminoisobutyric acid and L-phenylalanine were measured. The diet based on peanut oil (deficient in n-3) caused a greater blood-to-brain transport of sucrose but not of alpha-aminoisobutyric acid or L phenylalanine. These observations indicate that regardless of the mechanisms involved, alterations in essential fatty acids induced by diet can modulate to some extent the blood-brain transport of hydrophilic molecules without a carrier. PMID- 1625823 TI - A study of New Zealand wood workers: exposure to wood dust, respiratory symptoms, and suspected cases of occupational asthma. AB - A randomly selected group of 50 New Zealand wood workers was studied. The level of airborne wood dust to which they were exposed ranged from 1.0-24.5 mg/m3. The wood workers reported experiencing higher rates of both lower and upper respiratory tract symptoms than a control group of office workers. Inhaled wood dust, in particular from rimu (Dacrydium cupressinum), was frequently cited by workers as being associated with respiratory tract symptoms. The wood workers' responses to the respiratory symptom questionnaire, and serial recordings of peak expiratory flow rate were used to screen the group for suspected cases of occupational asthma. Five cases fulfilled the study's criteria for suspected occupational asthma. In four of these, further evidence was found to support this diagnosis. We conclude that exposure to wood dust may cause occupational asthma in the woodworking industry in New Zealand. PMID- 1625824 TI - The effect of employment status and household composition on health care utilisation in a general practice. AB - OBJECTIVE: to investigate the effect of employment status and family composition on general practice and secondary health care utilisation rates of a New Zealand general practice population. METHODS: the study practice's health care records were electronically interrogated and pooled data on utilisation rates was obtained for a 12 month period. Individual records were grouped according to the number of people in the family and families were further categorised according to the employment status of the adults in the family. Comparisons were made between family groups in rates of general practice and secondary care activities. Costs were attributed to each activity and a cost analysis undertaken. RESULTS: families of four or more people depending on government benefits had a lower primary care cost per person than equivalent families where an adult was in paid employment, but higher costs in secondary care resulted in a higher total health care cost. Overall, for the year reviewed, the mean cost per person for public health care was $365 for people in families where at least one person was in the paid workforce, $568 for those in families depending on government support, and $1438 for people over 60 years of age. CONCLUSION: in this practice the increased use of secondary care facilities by those who have lower rates of general practice activity resulted in a higher overall cost of health care to those patients. This study indicates the need for further analyses of activities by differing patient groupings to facilitate rational and equitable health care planning. PMID- 1625826 TI - Does methionine alter the outcome in halothane hepatitis? PMID- 1625825 TI - Chronic pain and the use of health services. AB - The range and extent of health consulting by people who have chronic pain attending a specialist clinic was assessed. Forty-two subjects attending Auckland Hospital pain clinic completed a questionnaire about their use of conventional and complementary health services for their pain in the previous 12 months. The general practitioner was the most frequently consulted health professional, visited, on average, 12.9 times per annum; compared with the expected rate of 4.2 consultations per annum. Medical specialists and health professionals had been consulted more frequently than complementary specialists. Twenty-five percent of the sample had been admitted to hospital for investigations relating to their pain in the previous year. On average, these patients spent $1333.63 per annum of their personal funds on health care. The cost of health care for chronic pain is significant both for the individual and the state and highlights the need for intensive pain management programmes. PMID- 1625827 TI - You can't ask if you don't know what to ask: a survey of the information needs and resources of hospital outpatients. AB - OBJECTIVES: to test public demand for health and sickness information and identify sources of information used by the public. METHODS: using a questionnaire as the basis of a highly structured interview, 274 outpatients or their caregivers from nine clinics in Wellington Hospital, attending for the second or subsequent time, were asked whether they felt they knew enough about their illness and treatment, and where they had obtained their information. RESULTS: almost half expressed a wish for more illness information and two-fifths wanted to know more about their treatment. Respondents were significantly more satisfied with treatment than illness information. Outpatient comments further indicated dissatisfaction with information. Sixteen sources of information were each used by four or more people, almost 20% of the sample using more than six sources. Health professionals, the hospital doctor in particular, were the most important source of information; informal personal contacts were also widely used. CONCLUSIONS: the results highlight the difficulties of communication between health professionals and clients. The possibility of cooperation between health and information professionals in providing patients with more information is raised. PMID- 1625828 TI - Down-sizing of hospitals with effective community care. PMID- 1625829 TI - Baseline risk for asthma deaths. PMID- 1625830 TI - Illegal vacancy advertisement? PMID- 1625831 TI - Iron deficiency. PMID- 1625832 TI - Outpatients appointments. PMID- 1625833 TI - Waiting lists. PMID- 1625834 TI - The new health changes: views from top nurses. PMID- 1625835 TI - Breathing easier. PMID- 1625836 TI - Getting ahead. PMID- 1625837 TI - Converting technology resistors and hesitators into users. PMID- 1625838 TI - Protecting the rights of computer artisans. PMID- 1625839 TI - Maximizing the probability that purchased software will be used. PMID- 1625840 TI - Getting funded by the Helene Fuld Health Trust. PMID- 1625841 TI - Practice nurses and OH. PMID- 1625842 TI - Corporate manslaughter--what next? AB - Corporate manslaughter is a relatively new concept, but with the catalogue of tragic disasters in recent years it is an idea that is gathering increasing support. Gillian Howard examines the legal basis for such an action. PMID- 1625844 TI - Working with display screen equipment. PMID- 1625843 TI - Building a healthier workforce. AB - The European Year of Health has put the construction industry at the top of its agenda. Sarah Evans examines the challenge presented to OH practitioners in this field and looks at the ground-breaking work of OHN, Mike King. PMID- 1625845 TI - Debriefing victims of violence. AB - Public sector unions have been warning for some time about the effects of violent incidents on their members. OH clinical psychologist, Martin Bamber (right), believes that psychological debriefing can help victims of workplace violence and prevent long term problems. PMID- 1625847 TI - AIDS update. New infections. PMID- 1625846 TI - Osteopathy: the 'orthodox' alternative. AB - Janice Kaye believes that osteopathy can significantly reduce employee absenteeism. Here she explains its unique system of treatment and argues for its use in OH departments. PMID- 1625848 TI - Impairment in health professionals: misunderstood and mistreated. PMID- 1625849 TI - [PHysiological function of veins and their intrinsic regulation]. AB - Physiological functions of the veins include: 1. Blood collectors with flow rectifying valves; 2. Selective barrier function, venular reabsorption of fluid; 3. Capacity function and redistribution of the blood volume, pressure-damping; 4. Maintaining the filling pressure of the heart by adequate venous return at varying cardiac output; 5. Increasing orthostatic tolerance of the body; 6. Postcapillary resistance; 7. Angiogenesis (in venous side of the microcirculation); 8. Secretion of bioactive substances by the endothelial and smooth muscle cells; 9. Lymphocyte homing (high-endothelial venules); 10. Cooperation between venular endothelium and the polymorphonuclear leukocytes (margination and rolling); 11. Enhanced inhibition of platelet aggregation and thromboembolic reactions; 12. Other special functions (e.g. facial vein: contribution to cranial thermoregulation; internal jugular vein: antisiphonage "device", etc.). Recent results suggest: 1. that intrinsic biomechanical adaptation of the systemic vein wall may occur in response a) to fast pressure changes within the physiological range by myogenic capacity autoregulation of the lumen; b) to long-term physiological haemodynamic loading by increase in total capacity and in short-term myogenic autoregulation range without marked changes of the wall thickness; c) to chronic arterialization with compensatory increase in wall-thickness reducing the extreme mechanical stresses induced by arterial pressure (such changes also imply fibrotic transformation of the wall-structure); 2. EDRF physiologically released by venous endothelium seems to be an important factor protecting the veins against non-desirable increases of smooth muscle tone (e.g. at low Mg-ion level of extracellular fluid, or in case of axial overstretch of the vein, etc.). PMID- 1625850 TI - [Study of the virulence of coagulase-negative staphylococci in experimental infections]. AB - The pathogenicity and virulence of 3 strains of Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus saprophyticus, respectively were studied in BALB/c mice by intraperitoneal (ip) challenge using 4 bacterial suspensions of different colony forming units (CFU) of each strain. Strains were isolated from wound, blood, and urine of inpatients. On the base of the lethality rates, S. saprophyticus proved to be the most virulent (LD50 = 2.7-2.9 x 10(7) CFU/g body wt), while the S. epidermidis species was the least virulent (LD50 = 6 8 x 10(7) CFU/g body wt). The lethality rate of male mice was higher than that of the female ones at the same challenge bacterium concentration. Mice of higher body weight were generally more sensitive to a quality of bacteria calculated to 1 g of mice than the lighter mice. The 245 mice surviving the challenge were dissected at the 10th day of infection. Splenomegaly was found to be the most frequent macroscopic pathological alteration. There appeared kidney abscesses, liver abscesses, and rarely peritoneal abscess. The frequency of pathological findings were directly proportional to the amount of bacteria injected. The results indicate that clinical strains of coagulase-negative staphylococci (CNS) examined were pathogenic and virulent for BALB/c mice they are invasive after ip injection and can cause macroscopic pathological changes in parenchymal organs. Thus, ip CNS challenge in mice may be a model to imitate and study infections caused by CNS in human. PMID- 1625851 TI - [Epidemiologic aspects of osteoporosis and fractures in advanced age]. AB - The most important word-wide and home trends of osteoporosis and age-related fractures are reviewed. The author summarizes the relationship between fractures and bone mass, the bone mass determinants and the risk factors for osteoporosis. He describes the secular trends, age- and sex specific incidence as well as geographic distribution of fractures of the proximal femur, vertebrae and distal forearm. Finally the social and financial impact of this major public health problem are discussed. PMID- 1625852 TI - [Hand fractures and epiphyseal injuries in childhood]. AB - Anatomic features of the hand in childhood are presented that are responsible for the types of certain injuries. On the basis of the data in the literature and of the authors' own experience of 92 cases the main points of the diagnosis and therapy of metacarpal and phalanx fractures are summarized. The possibility of finger-replantation is also mentioned. Their statements are illustrated by their own cases. In order to recognize late growth disturbances, the necessity of the follow up is emphasized. PMID- 1625853 TI - [Basal cell carcinoma of the leg with metastases to the surrounding skin and inguinal lymph nodes]. AB - A case of metastasizing basal cell carcinoma in a 57-year-old male is described. The primary tumor localised on the left lower leg metastasized to near skin and inguinal lymph nodes. The primary and metastatic skin tumors were excised and the defects covered by free skin grafts. Besides, the inguinal lymph nodes were block dissected and a part 10 cm long of the left calf bone was resected. PMID- 1625855 TI - [Medical ethics? Oh!]. PMID- 1625854 TI - [Lymphomatoid granulomatosis]. PMID- 1625856 TI - [Pathology--on a molecular level (determination of nucleic acids from fixed embedded samples)]. AB - Molecular biological techniques may open new avenues to pathological archives. Fixed and paraffin embedded blocks are a suitable source of nucleic acids, especially of DNA, for retrospective analysis. The quality of DNA depends mainly on the fixation procedure. High molecular weight DNA allows Southern hybridization, but fragmented DNA also became a target with the appearance of polymerase chain reaction (PCR). PCR has rising applicability and enables amplification of required sequence even from one section. Using these techniques on archieved materials a wide variety of informations, e.g. correlation between morphology, phenotypic expression and gene alteration, will be available. PMID- 1625858 TI - [Can gastroesophageal reflux be prevented by inducing a scar tissue ring around the cardia?]. AB - Severe gastroesophageal reflux was accomplished in 18 dogs by circular cardiomyectomy. After this intervention a Vicryl scarf was placed around the cardia in 12 dogs. The Vicryl scarf was absorbed within 6 months and in its place remained a scarred tissue. In the follow up gastroesophageal reflux could not be detected by manometry, pH-metry, radiology and endoscopy. In the control group all 6 dogs died within 3 weeks due to complications of gastroesophageal reflux. On the basis of these data the Vicryl scarf implantation is an effective, simple, new antireflux operation which can be initiated into the human surgical practice. PMID- 1625857 TI - [Gonadotropin releasing hormone loading test with bromocryptin therapy: a new possibility in the differential diagnosis of normo-prolactinaemic anovulation]. AB - An anovulation group with normal basal prolactin level (less than 600 mU/l) was found during GnRH loading tests. After GnRH administration there was a definite increase in prolactin value together with an insufficient hypophyseal response. Bromocriptine treatment was commenced on the 10th day (daily 2.5 mg) before carrying out the GnRH loading tests again. During the repeated tests prolactin levels remained normal, basal FSH and LH values increased and reactive hypophyseal responses occurred. On the basis of the examination a group ("latens hyperprolactinemia") responding with increased prolactin production during GnRH administration was found. This higher prolactin level inhibits gonadotropin release from hypophysis. In these cases ovulation induction with bromocriptine is adviseable in spite of basal prolactin level is normal. PMID- 1625859 TI - [Polythelia and renal malformation]. AB - The authors found 241 polythelia (5.86) among 4113 schoolchildren (aged 6-14 years). They investigated 236 of the 241 with ultrasound and found 10 renal malformations (4.24%). Among 280 controls with respiratory infection, accident or tonsillectomy they found 9 renal malformations (3.21%). With screening of 1635 neonates they found 66 with accessory nipples (4.05%). Two of the 66 had renal malformations (3.03%), while among the 1957 control neonates 37 had renal malformations (1.89%). In the hospital and ambulancy the authors found 106 polythelia, five of them had renal abnormalities (4.72%). The authors did not found association of polythelia and renal malformation with ultrasound investigation of 408 children with polythelia. PMID- 1625860 TI - [A case of numerous foreign bodies found in the esophagus and the right main bronchus]. AB - The authors report about the elimination of foreign bodies fixed in the oesophagus and aspirated into the right main bronchus. They discuss the diagnostic work and the ways of its elimination. They emphasize the importance of cooperation between the endoscopist and the surgeon. PMID- 1625861 TI - [Istvan Hollos]. PMID- 1625862 TI - [Cardiovascular diseases in the Bible]. PMID- 1625863 TI - Epidemiology, pathogenesis, and genetics of acoustic tumors. AB - This article reviews the epidemiology of both unilateral and bilateral (NF-2) acoustic tumors. The growth rate of acoustic tumors is examined from a clinical, radiographic, and laboratory perspective. The anatomic, histologic, and biochemical considerations as well as the influences of sex hormones on acoustic tumor formation are reviewed. Also presented are an update on the laboratory search for the NF-2 gene on chromosome 22 and recently identified DNA markers. Predictions are made concerning the potential future applications of genetic testing for prenatal or presymptomatic diagnosis of the disease that causes bilateral acoustic tumors. PMID- 1625864 TI - Clinical manifestations and audiologic diagnosis of acoustic neuromas. AB - If an AN is suspected, a detailed patient history and a thorough otologic and neurotologic physical examination should be carried out. The first echelon of diagnostic testing begins with a pure tone audiogram, speech reception threshold, speech discrimination testing, and acoustic reflex testing. If the clinician is even moderately suspicious of the presence of an AN, the patient should undergo a Gd-MRI scan. If suspicion is low, an ABR should be performed, and if negative, the patient should be reevaluated periodically. PMID- 1625865 TI - Imaging of acoustic neuromas. AB - A negative high-quality, high-resolution, contrast-enhanced MRI scan is excellent evidence that a patient does not have an AN. Most nerve sheath tumors have a characteristic appearance, and when a tumor is detected there is seldom any doubt as to the identity of the lesion. There are other causes of enhancement, however, or of high signal that can be mistaken for an AN, and these must be kept in mind when a case is considered positive. In some cases, it may be appropriate to defer surgery to clarify a questionable finding by obtaining a follow-up scan. CT is still a reliable examination. In addition to evaluating the IAC, valuable information about the architecture of the petrous bone and labyrinth is provided. Improvements in imaging technology are occurring at a rapid rate. Thinner slices and more rapid scan techniques will make MRI even more useful in evaluation of the IAC. PMID- 1625866 TI - Hearing preservation in acoustic tumor surgery. AB - Preservation of hearing is a realistic goal, possible through the retrosigmoid or middle fossa surgical approaches. The best candidates have small tumors and good preoperative hearing. Preoperative ABR, ENG, and imaging characteristics may help prognosticate chances for hearing preservation. Hearing rarely improves after surgery, and some have noted a decline in the preserved hearing over time. With the introduction of gadolinium-enhanced magnetic resonance imaging, a larger number of small acoustic tumors are being diagnosed before hearing has been significantly affected. These patients benefit from this early diagnosis and are the best candidates for hearing preservation surgery. PMID- 1625867 TI - Facial nerve outcome in acoustic neuroma surgery. AB - Patients consider facial paralysis the most concerning sequelae following acoustic tumor resection. Surgical and anesthetic refinements have lowered operative mortality to allow the surgeon to focus on preserving facial nerve function. Tumor size, microsurgical technique, and intraoperative monitoring are the most important factors that define the risk of postoperative facial paralysis. A protocol for uniform surgical reporting is proposed. PMID- 1625869 TI - Management of ophthalmic complications of facial nerve palsy. AB - Six stages--supportive care (with or without tarsorrhaphy), planning for facial reanimation, lower eyelid and lateral canthal resuspension, passive upper eyelid reanimation, dynamic eyelid reanimation, and soft tissue repositioning--should be considered in the management of the ophthalmic complications of facial nerve palsies. Each stage should be considered in order, although action in each stage may not be appropriate for all patients. In addition, after appropriate consideration, two or more staged procedures may be performed at the same time. Treatment may be held at any stage in which the cornea is compensated and the patient is comfortable and happy. By employing this staged approach, the surgeon has a method of organizing therapy in a logical fashion, and the patient is offered a set of reassuring goals, which combine to make the treatment plan more effective. PMID- 1625868 TI - Reanimation of the paralyzed face. AB - The challenge of reconstruction in the paralyzed face is to provide symmetry both at rest and in active expression. Although functional considerations must take precedence, the patient with unilateral facial palsy faces social stigmata that are exceptionally difficult. The best reconstructions in late paralyses fall far short of natural facial expression. Conley, one of the pioneers in facial nerve rehabilitation, reflected the frustration of dealing with limited techniques: It has been assumed by many surgeons that involuntary emotional communication is through the facial nerve, but this has never been substantiated. Indeed, emotional expression may be beyond our concept of a mere physical tract. It certainly has never been totally restored by any surgical technique that attempts to rehabilitate the face. When injury to the facial nerve is established, early nerve grafting on the ipsilateral side is the best treatment. In acoustic neuroma and other intracranial operations, the only real opportunity for grafting or repair is at the time of the procedure. If the nature of the injury is uncertain, a period of 12 months is allowed to elapse before consideration of intervention, which should be started if there is no return of function at that point. Electromyography may be of assistance in assessing minimal early return; if any early return is noted, further waiting is indicated. If there is no return at 1 year, cranial nerve XII to VII crossover will preserve facial muscle tone and permit a more measured decision-making approach. Patients with multiple cranial nerves involved may be candidates for a partial hypoglossal transfer using a nerve graft, to attempt to preserve swallowing. In selected cases, cross-facial nerve grafting to the preserved facial muscles will give excellent results and obviate the need for local or distant muscle transfers. When treating established paralysis of long duration, cross-facial nerve grafting with microneurovascular muscle transfer is the best option for symmetrical movement of the face. Temporalis and masseter muscle transfers should be reserved for the patient with intercurrent medical disease or the patient who refuses additional operations or operative sites. Static slings and other related procedures should be considered adjunctive but not primary treatment in the vast majority of cases. Although there are limitations in each of the procedures described, close cooperation between the otolaryngologist, the neurosurgeon, and the plastic surgeon can provide many patients with satisfactory rehabilitation from facial paralysis. PMID- 1625870 TI - Conservative management of acoustic neuromas. AB - The results of this study and others document the biologic behavior of acoustic neuromas. In view of the evidence presented, which describes both variable rates of individual tumor growth and spontaneous regression in size, it would seem prudent that before selecting a nonsurgical treatment modality, the growth rate for the particular tumor in question should be established. To date, none of the literature that addresses the use of focused irradiation has attempted to do so. Our study as well as those of others suggests that the growth rate of acoustic neuromas becomes predictable over time. Based on this observation, a conservative (nontumor excision) management strategy is proposed for selected individuals. Patients to whom this management philosophy has been recommended or who themselves have chosen this option are seen twice yearly. Each visit consists of a thorough neurotologic examination as well as high-definition CT or MRI. Careful comparison of the clinical course as well as calculation of the tumor size is carried out in each instance. If the clinical course and rate of tumor growth remain unchanged over a 3-year follow-up, annual assessments are recommended. In the event of tumor enlargement, surgery may or may not be recommended, depending on the rate of growth and the age of the patient. Our experience suggests that a rate of growth equal to or exceeding 0.2 cm per year constitutes an indication for tumor removal. PMID- 1625871 TI - Meningiomas, epidermoids, and other nonacoustic tumors of the cerebellopontine angle. AB - Nonacoustic tumors of the CPA include meningioma, epidermoid, arachnoid cyst, lipoma, facial nerve schwannoma, and metastatic tumor, among others. Like AN, these lesions present with audiovestibular symptoms, facial nerve dysfunction, and other cranial nerve neuropathies. Preoperative differentiation among these lesions based on clinical history, physical examination, and audiovestibular testing is difficult. CT and gadolinium-enhanced MRI reveal the characteristic appearance of these tumors and make accurate diagnosis possible. PMID- 1625872 TI - Health care reform--a nursing perspective. PMID- 1625874 TI - Researcher develops computer networks for AIDS and Alzheimer patients. PMID- 1625873 TI - AIDS in Pennsylvania. PMID- 1625875 TI - Making it the right time to be a nurse. Interview by Susan FitzGerald. PMID- 1625876 TI - Impaired professional program available to health care professionals. PMID- 1625877 TI - PNA position statement issued: unlicensed assistive personnel. PMID- 1625878 TI - A decision making model for determining RN/LPN scope of practice. PMID- 1625879 TI - Pennsylvania legislators' opinions about nurses and nursing. PMID- 1625880 TI - The effect of leadership style of emergency department nurse managers on job satisfaction of their nursing staff. PMID- 1625881 TI - OSHA regulations: do you know what protection is required? PMID- 1625882 TI - Author and hospice founder to address AIDS conference. PMID- 1625883 TI - Ferguson to keynote AIDS conference. PMID- 1625884 TI - ANA asks Congress for increased funding for nursing education & research. PMID- 1625885 TI - Educating nurses in political process: a growing need. PMID- 1625886 TI - Political action--an investment in the future. PMID- 1625887 TI - Pennsylvania Safe Kids Coalition features infant car safety. PMID- 1625888 TI - Role strain in patients and family experiencing cancer. PMID- 1625889 TI - Pre-employment mandatory testing for HIV. PMID- 1625890 TI - Laufband locomotion with body weight support improved walking in persons with severe spinal cord injuries. AB - After low transection of the spinal cord mammalian quadrupeds can be trained to walk on a driven surface indicating that coordinating neuronal circuits persist in the spinal cord segments caudal to the lesion. We trained 8 persons with incomplete spinal cord lesion on a Laufband (driven treadmill) for 1 1/2 to 7 months (5 days a week, 30-60 minutes daily) starting 5 to 20 months after injury and found significant improvement in the utilisation of the paralysed limbs during locomotion. Locomotion is described in one additional patient who had trained independently on parallel bars for several years. Five patients had complete functional paralysis in one lower limb when tested in a resting position. In EMG recordings voluntary activity (ie activity induced upon command) was absent or residual in the main flexor and extensor muscles of this limb. In contrast, during locomotion flexion and extension movements were performed and phasic EMG activity was present. In these 5 patients, and in all others reported here, skin sensibility and proprioception are preserved to different degrees in all limbs. In the course of locomotive training of 4 severely paralysed patients the initially habituating flexion reflexes could be entrained in the paralysed limbs as was the case for knee extension during stance. Subsequently, initial body weight support (BWS) of 40% could be reduced to 0%. The distance covered on the Laufband (0-104 m in the first week) increased significantly (200-410 m) in the last week of training as did speed (0-10 to 14-23 m/min). More importantly, this training subsequently allowed patients to walk on a static surface for 100 to 200 meters while voluntary activity remained absent in the paralysed limb when tested at rest. Similar progress was achieved in the 4 less severely paralysed patients. The one patient who had trained independently on parallel bars for several years is described walking on a static surface for 40 meters with the help of a walker, though he had one completely and one near completely paralysed lower limb. It appears that bipedal stepping with consequent knee extension and stabilisation can be taught after unilateral complete or near complete loss of voluntary activity, suggesting the manifestation of complex reflex motor patterns at the spinal level. PMID- 1625891 TI - Ambulation using the reciprocating gait orthosis and functional electrical stimulation. AB - Until recently, rehabilitation engineering offered 2 different methods to improve daily living independence for spinal cord paralyzed subjects. One, the use of various orthotics and the other, the application of functional electrical stimulation. In the present work we chose to combine reciprocating gait orthosis (RGO) with functional electrical stimulation (FES) into one hybrid system. A detailed biomechanical and clinical instruction for the use of this system is given. Results obtained from application of the hybrid system on a complete T4 paraplegic patient demonstrate that the most significant contribution was the reduced invested energy cost required for stand-up and for ambulation. PMID- 1625892 TI - Physiological cost index of paraplegic locomotion using the ORLAU ParaWalker. AB - Energy expenditure is an important parameter in the assessment of gait and orthotic treatment of locomotor disabilities. Up until now oxygen uptake measurement has been the most common method used to assess this. In able bodied subjects heart rate monitoring is also increasingly used. In high thoracic level lesion paraplegics monitoring heart rate was considered to be unreliable because of suspicion of injury to the sympathetic contribution to the cardiac plexus. Bar On & Nene found that in paraplegics below the lesion level T3 heart rate still shows linear relation to oxygen uptake. MacGregor combined the heart rate and speed of locomotion to produce a single index called physiological cost index. This study consists of monitoring heart rate and speed of 16 adult thoracic level paraplegics walking with the ORLAU ParaWalker, calculation of their physiological cost index, and establishing a range of physiological cost index of paraplegic locomotion using the ORLAU ParaWalker. PMID- 1625893 TI - Voiding by increased abdominal pressure in male spinal cord injury patients--long term follow up. AB - We reviewed the long term follow up of five spinal cord injury patients with detrusor areflexia who emptied their bladder using high abdominal pressure. Ages ranged from 29 to 58 years, and the mean time elapsed from injury was 18.9 years. The bladder pressure during voiding ranged from 95 to 160 cm of water. One patient developed vesicoureteral reflux and hydronephrosis. Long term monitoring is suggested in patients who use high abdominal pressure for bladder emptying. PMID- 1625894 TI - Bladder outlet resistance decreasing operations in spinal cord damaged patients with vesicoureteral reflux. AB - Bladder outlet resistance decreasing operations were carried out on 68 spinal cord damaged patients with 87 vesicoureteral refluxes in the Paraplegic Centre, Hamburg, from 1982 to 1988. These patients were studied regularly with infusion urography and voiding cystourethrograms combined with urodynamic procedure. Although the primary aim of the operative treatment was to achieve balanced voiding, 62 (71%) refluxes disappeared, 10 (12%) changed for the better, 13 (15%) stood unchanged and 2 (2%) worsened. It was observed that the results of operative treatment of secondary vesicoureteral reflux depend only on the recuperative capacity of ureterovesical junction after reducing the pathologically increased bladder outlet resistance. Successful treatment of secondary vesicoureteral reflux does not influence renal parenchymal scarring. In all of the patients with unchanged or worsened reflux balanced voiding has still not been achieved, the bladder outlet resistance being not sufficiently decreased. PMID- 1625895 TI - Exertional hypotension in thoracic spinal cord injury: case report. AB - Exertional hypotension is well described in quadraplegics, but there are few descriptions of this hemodynamic response in paraplegics or of treatment modalities to correct this condition. We describe a patient with a complete T3-4 spinal cord lesion who repeatedly demonstrated symptomatic hypotension with wheelchair sports and arm ergometry. We used gas exchange analysis and exercise echocardiography to delineate the mechanism for hypotension. These results enabled us to develop a simple treatment plan consisting of abdominal binding and elastic stockings to avoid recurrent symptoms. PMID- 1625896 TI - The effectiveness of a pressure clinic in preventing pressure sores. AB - The role of a pressure clinic in reducing the incidence of pressure sores is described. Interface pressures are routinely measured to ensure that appropriate cushioning is provided. In patients most at risk, thermography is also valuable to ensure that the blood flow to the skin is not compromised. The implementation of such a clinic has proved successful and has resulted in a reduction of over 50% both in the incidence of sores and in the admission rate due to sores, when compared with studies from other spinal units. PMID- 1625897 TI - The role of intracavernosal vasoactive agents to overcome impotence due to spinal cord injury. AB - Twenty-two spinal cord injured men (mean age 35.2 years) referred because of impotence were treated with intracavernosal vasoactive agents. Papaverine 2-20 mg, papaverine 40 mg plus phentolamine 0.5 mg or prostaglandin E1 (1-20 micrograms) were used. Nineteen responded and were taught to self administer the medication with varying degrees of assistance from their partners. Fourteen men participated in a postal survey; 12 (86%) continued to use the drugs every 1 to 4 weeks and reported satisfaction with the method. Partner responses were positive in half of the group and when not so it influenced the patients to abandon or reduce the frequency of treatment. Counselling was essential to allay anxiety. Clinical management was not compromised and side effects were minimal. Overall we found this treatment effective, safe and worthwhile. PMID- 1625898 TI - Ossification of the posterior longitudinal ligament in the thoracic spine causing intermittent paraplegia in an Englishman: case report. AB - Compression of the spinal cord due to ossification of the posterior longitudinal ligament (OPLL) often leads to quadriplegia or paraplegia in Japanese patients. This disease is uncommon in other races. We report the case of a middle-aged Englishman who presented with complaints of intermittent paraparesis due to OPLL at the T5-T6 level in his thoracic spine. PMID- 1625899 TI - Health and psychosocial issues of individuals with incomplete and resolving spinal cord injuries. AB - Longitudinal data and clinical experience indicate that a greater proportion of spinal cord injuries result in incomplete or resolving neurological lesions. Although it has been reported that persons with incomplete injuries enjoy better functional outcomes, routine contacts with these individuals indicate that many experience problems and complications strikingly similar to those with complete spinal cord injuries. Thus, to document the issues and needs of these individuals, data from Colorado's population-based spinal cord injury surveillance program were analyzed. Of 330 persons registered since January 1, 1986, 121 (37%) were found to be minimally disabled (Frankel class D or E). Review of medical records and follow up documentation for these individuals indicated that although over 75% were ambulatory and virtually all were physically independent, more than 80% did report problems in one or more areas: 21% had orthopedic issues and 17% faced additional spinal surgery; 16% reported neurological deterioration or increased spasticity; 25% had pain problems; and 16% had bladder difficulties. Other issues included bowel problems, blood pressure abnormalities, skin breakdown, sexual difficulties, depression, and unemployability. Implications for rehabilitation are discussed in the light of these and other findings. PMID- 1625900 TI - A second traumatic spinal cord injury: associated risk factors. Case report and review. AB - Despite advances in acute care and long term management, traumatic spinal cord injury remains a devastating and disabling event. This report describes the case of a second traumatic spinal cord injury in a previously rehabilitated and functionally independent paraplegic. Factors potentially associated with the second spinal cord injury in this patient include wheelchair use, previous spinal fusion, alcohol use and sensation-seeking behavior. These factors, which are common to many spinal cord injured patients, could potentially be risk factors for a second traumatic spinal injury. PMID- 1625901 TI - Preoperative embolisation, transpedicular decompression and posterior stabilisation for metastatic disease of the thoracic spine causing paraplegia. AB - During a brief period from March 1988 to January 1990 we were faced with 13 patients with malignant vertebral neoplasms (metastasis) of the thoracic spine. Nine of these had progressive extradural spinal cord compression with motor, sensory and sphincter involvement of varying degrees and duration. After proper evaluation these 9 cases were aggressively managed by preoperative embolisation of the tumour, transpedicular decompression and a same stage posterior metallic fixation. The immediate results were encouraging, with 2 patients showing total recovery and 3 showing partial recovery. All of the 9 operated cases were pain free postoperatively and could sit up unaided and be easily transferred to the Cancer Institute for back up chemotherapy and radiotherapy. They also improved psychologically, and cooperated well in their subsequent rehabilitation programme. PMID- 1625902 TI - The role of motor evoked potentials in the management of hysterical paraplegia: case report. AB - The role of motor evoked potentials in the management of a case of presumed hysterical paraplegia precipitated by spinal injury in a man with a previous history of surgery for scoliosis is presented. Motor evoked potentials were elicited with magnetic stimulation 12 days after injury and were within normal limits. The presence of normal motor electrophysiology and observation by the patient of involuntary movement of the lower limbs during stimulation greatly facilitated the patient's management. These findings are discussed with reference to current diagnostic investigations in the presence of a suspected diagnosis of hysterical paraplegia. PMID- 1625903 TI - Examination of murine antibody response to secondary hydatidosis using ELISA and immunoelectrophoresis. AB - Antibody responses in mice with up to 64 weeks of secondary Echinococcus granulosus hydatidosis were examined by ELISA using hydatid protoscolex antigen (Px), Antigen 5 (Ag5) and Antigen B (AgB), and by immunoelectrophoresis (IEP) using sheep hydatid cyst fluid (SHCF). Anti-Px IgG antibodies, evident from 3-5 days post infection (p.i.), increased steadily until 16 weeks and maintained a high level afterwards. Anti-Ag5 IgG antibodies were negligible up to two weeks, but they showed a small increase around 2-3 weeks which was followed by a big increase around 16 weeks p.i. The high level of anti-Ag5 IgG antibodies persisted to the end of experiment. The level of anti-AgB IgG antibodies remained relatively low throughout infection. Anti-Px IgM antibodies appeared in the early period of infection, but became insignificant as the infection proceeded. Specific IgM antibodies to Ag5 and AgB showed two waves of increase, one between 3 days to 4 weeks p.i. and the other between 16 weeks to 46 weeks p.i. The level of IgA antibodies to Ag5 and AgB was low and only a moderate amount of anti-Px IgA antibodies was detected. Generally, a higher level of serum antibodies are associated with a larger number of mature cysts. Serum samples from 5 of 8 mice harbouring hydatid cysts formed 1-3 bands with SHCF in IEP, including Arc 5, but a precipitation are with AgB was not observed. Analysis of hydatid cyst fluid from the infected mice (MHCF) in IEP also failed to demonstrate AgB. Despite the high levels of antihydatid antibodies generated in the infected mice, protoscoleces appeared to be unhindered in their growth to mature cysts. PMID- 1625904 TI - Immune responses of sheep to surface antigens of infective larvae of Ostertagia circumcincta. AB - Immune responses to surface antigens of infective larvae of Ostertagia circumcincta were studied in 5-month old Finn-Dorset male lambs. The sheep were vaccinated subcutaneously with 2 doses of 25 micrograms/kg body weight of infective larvae surface or somatic extracts and Freund's or beryllium hydroxide adjuvants. It was found that only in lambs vaccinated with L3 surface extracts and beryllium hydroxide as an adjuvant did worm burdens differ significantly (P less than 0.01) from those of challenge controls (71.7% protection). Sheep vaccinated with the same antigenic preparation but administered with Freund's adjuvant or with beryllium adjuvant and somatic extracts demonstrated rather poor protection (32.4 and 30.5% respectively). All the vaccinated sheep showed a high IgG response to L3 surface antigens while significant levels of serum and bile IgA reacting with the surface extracts were only detected in those lambs vaccinated with L3 surface extracts and beryllium hydroxide. In immunofluorescence tests serum IgA of this group reacted with the whole surface of exsheathed larvae or with the site of opening of excretory pore while IgG antibodies reacted strongly with the anterior and posterior parts of the infective larvae. Both IgA and IgG responses to surface antigens were stage specific. PMID- 1625905 TI - Alternative patterns of MHC-restricted antibody responsiveness following intraperitoneal immunization of inbred mice with different preparations of an 86 kilodalton antigen of Schistosoma mansoni. AB - The investigation of MHC restricted antibody responses to an 86 kDa antigen (p86) during chronic Schistosoma mansoni infection has been extended to immunization with this antigen. In the absence of adjuvant, a similar pattern of responsiveness by mice expressing H-2k and H-2d but not H-2b was observed following immunization with unpurified adult worm homogenate. Adjuvant selectively abrogated the capacity of H-2d mice to respond and this was also the case when purified p86 with adjuvant was injected. Immunization with purified subfragments of p86 again demonstrated MHC restriction in the capacity to immunoprecipitate p86 in vitro translation product, the pattern varying according to the fragment used. Western blot analysis showed that in some, but not all instances of apparent 'non-responsiveness' characterized by immunoprecipitation, antibody specificities capable of recognizing p86 epitopes on the nitrocellulose bound p86 were, indeed, present. Thus the fine specificity as well as the absolute capacity to respond is influenced by both the MHC haplotype of the host and the nature of the immunizing antigen. PMID- 1625906 TI - Vaccination of dogs against Babesia canis infection using parasite antigens from in vitro culture. AB - Groups of five dogs were vaccinated with different Babesia canis vaccine formulations. It appeared that partial protection against challenge infection was obtained when using parasite antigens from in vitro culture in combination with saponin. Protection was evident as a decrease in parasitaemia after challenge and was associated with the presence of serum antibodies against Babesia parasites. In addition, parasite antigen derived from in vitro culture supernatant exhibited more protective activity than somatic parasite antigen, in that a less marked fall of haematocrit values was found after challenge infection. The fall of haematocrit value observed in the animals immunized with somatic parasite antigen was not different from that observed in the adjuvant control group. PMID- 1625907 TI - Testosterone-unresponsiveness of existing immunity against Plasmodium chabaudi malaria. AB - Testosterone (Te) is known to suppress immunity and to increase host susceptibility to many parasites. This study investigates the action of Te on immunity acquired against blood-stages of the malaria parasite Plasmodium chabaudi in female mice of the inbred strain C57BL/10. Our data show: (i) About 90% of mice infected with 10(6) P. chabaudi-infected erythrocytes are able to develop protective immune mechanisms which become evident in self-healing the infection. The capability of self-healing is lost when mice are pretreated with Te for 3 weeks. (ii) Mice which have self-healed infections acquire immunity to homologous rechallenge. Concomitantly, mice become Te-unresponsive in that their acquired immunity is not suppressible by Te-treatment. (iii) Flow cytometry reveals that Te-pretreatment entails an increase of CD8+ cells and a decrease of Ig+ cells by about 4% in spleens of non-immune mice. In immune mice, however, there is a Te-unresponsiveness of the percental distribution of splenic cell populations. (iv) Adoptive transfer experiments indicate that immunity is conferred by spleen cells, presumably non-T-cells. These cells are Te unresponsive, since they exert their effect in Te-pretreated mice in the presence of Te. (v) Te-unresponsive immunity can be also transferred by serum, especially the IgG-fraction, obtained from immune mice. Our data demonstrate that Te prevents the development of protective immunity against P. chabaudi infections. However, when once established, protective immunity becomes unresponsive to Te. Our data suggest that the effector mechanisms of protective immunity involve Te unresponsive B cells secreting protective IgG-antibodies. PMID- 1625908 TI - Naturally acquired cellular and humoral immune responses to the major merozoite surface antigen (PfMSP1) of Plasmodium falciparum are associated with reduced malaria morbidity. AB - We have investigated the pattern of acquired immune responses to the major surface protein of Plasmodium falciparum merozoites (gp 190, PfMSP1) in a malaria endemic population in West Africa. A prospective longitudinal study in 3- to 8 year-old children was conducted to examine the relationship between naturally acquired immune responses to PfMSP1 and subsequent susceptibility to malaria infection and clinical disease. A population cross-sectional survey was performed to investigate changes in immune response with age. The prevalence and concentration of antibodies to all regions of the molecule increased with age with the highest prevalence of antibodies being detected against regions of the molecule which are highly conserved between parasite isolates. In vitro lympho proliferation and interferon-gamma production in response to recombinant proteins representing polymorphic regions of the molecule also increased with age. Interestingly, proliferative responses to some regions of the molecule, including some highly conserved sequences, were highest in young children and decreased markedly with increasing age. Significant associations were observed between antibody and lymphoproliferative responses to proteins from the C terminus of the molecule and resistance to episodes of fever associated with high parasitaemia in partially immune children. In addition, high concentrations of antibodies to a conserved region close to the N terminus of PfMSP1 were also significantly associated with protection. PMID- 1625909 TI - Cats with single Brugia pahangi infections: relationship between parasitological status and humoral responses to somatic and surface parasite antigens. AB - Cats given a single inoculation of Brugia pahangi infective larvae (L3) were retrospectively allocated into three groups according to parasitological outcome of infection. Recognition of somatic and surface antigens of B. pahangi by sera from each group was compared by ELISA, immunoelectroblotting, and immunoprecipitation techniques. In cats that never became microfilaraemic mean serum IgG antibody levels against somatic extracts from adult male worms, L3, and microfilariae (mf) were higher than levels in cats that initially became microfilaraemic (mf + ve) then spontaneously became nonmicrofilaraemic (mf - ve). The lowest levels of antibody against each stage were found in cats that remained persistently mf + ve. Antigenic components of 18 kD and 22 kD in somatic extracts of adult worms and L3 were recognized by sera from cats that never became mf + ve and by spontaneously mf - ve cats, but not by sera of persistently mf + ve cats. When radioiodinated surface antigens of mixed adult worms and microfilariae were immunoprecipitated by sera from cats in the three groups, no correlation was observed between recognition of individual antigen components and parasitological outcome of infection. PMID- 1625910 TI - The ultimate balance: caring for yourself--caring for others. AB - We all know that caring is both a traditional as well as a contemporary value in nursing, and yet how many of us are as good at caring for ourselves as we are at meeting the needs of others? It's time the ethic of caring was expanded to include caring for the caregiver, as well as the more traditional emphasis on the patient's needs. Before you can care for others well, you must first know how to care for yourself. This article is an invitation to interact with the material. If you merely read the words you will miss the opportunity to reflect more closely on the balance between caring for others and caring for yourself. So take out a pen and some paper and spend some introspective time. Use this article as a mirror for personal reflection and a springboard for professional action. PMID- 1625911 TI - A brighter future for adults who have myelomeningocele--one form of spina bifida. AB - Recently a new population of adults with myelomeningocele, the most severe form of spina bifida, has emerged. Because of the complex issues challenging these adults, specialized health care services provided by a multispecialty team are recommended. With the hope that similar services will be developed, the establishment of one specific teen/adult spina bifida multispecialty team is discussed in this article. An overview of myelomeningocele is presented, which includes adult focused physical/cognitive/social-emotional challenges and goals, potential medical problems, and opportunities for nurse leadership. PMID- 1625912 TI - Postoperative orthopaedic blood salvage and reinfusion. AB - Minimal use of homologous blood is a desirable goal for both patients and health care providers. This article discusses one adjunctive technique that is used for the orthopaedic patient, postoperative blood salvage and reinfusion, and the implications for nurses. PMID- 1625913 TI - The physiologic changes of aging. AB - It is estimated that by the year 2030, 21.2% of the United States population will be 65 years of age or older. The elderly are the fastest growing segment of the population and use health care services extensively. Today 30% of all hospitalized individuals are elderly. The professional nurse must therefore be able to assess and assist elderly persons during the course of hospitalization. An important component of assessment is the ability to differentiate the normal physiologic changes of aging from the pathologic changes. To effectively intervene in a therapeutic plan of care the nursing professional must be aware of the limitations brought on by aging. PMID- 1625914 TI - Live and learn: patient education for the elderly orthopaedic client. AB - Patient education is a critical component of nursing interventions for health maintenance and illness prevention in assisting older persons with orthopaedic problems to maintain optimum independence and quality of life. This article focuses on the needs of the adult learner with emphasis on the elderly. Theoretical considerations of learning and characteristics of the adult learner are briefly introduced. Changes attributed to aging and factors that affect learning for elders are discussed. The article closes with strategies for planning effective patient education. PMID- 1625915 TI - Assessment of organizational culture: a tool for professional success. AB - Assessing the culture, or shared norms, of an institution to learn about its values, beliefs, and practices can be very useful in determining one's "fit" within an organization. It can also be helpful to those engineering change and to those interested in shaping an institutional image that attracts and retains qualified staff. This article discusses the concept of organizational culture, provides suggestions for assessment, and explicates this information through some familiar examples. Implications of organizational culture assessment are also discussed as they apply to the roles of staff nurse, nurse manager, clinical nurse specialist, faculty member, and nurse executive. Consideration is also given to nursing as a profession. PMID- 1625916 TI - Caring enough to bring about change. PMID- 1625917 TI - Enhancing orthopaedic nurses' clinical decision making. AB - Clinical decision making ability is necessary for safe and effective orthopaedic nursing practice. By clinical decision making, we mean the rendering of a judgment about patient care using analytical and intuitive processes and incorporating professional knowledge. Although recent research findings indicate that there is no single approach that clinicians use to make all decisions, there are several general aspects of decision making processes. Among these are the development of mental representations, decision-making procedures, and pattern recognition. Five selected strategies for enhancing these general processes are described and illustrated with patient situations relevant to orthopaedic nursing. PMID- 1625918 TI - Consumer advisory helps nurses talk to patients about AIDS. PMID- 1625919 TI - Nurses to be protected against AIDS, hepatitis B under new federal regulations. PMID- 1625920 TI - [Kinetics of myoglobin, creatine kinase and aspartate aminotransferase in uncomplicated and complicated forms of healing of experimental myocardial infarction]. AB - It was demonstrated in experiments on 60 dogs that in hyporeactive myocardial infarction (MI) myoglobin (MG) concentration and the activity of creatine kinase (CK) and aspartate aminotransferase (ASAT) increase at a slower rate and reach maximum values later. In hyperreactive MI the rate of their increase and the time of attainment of maximum values are, respectively, greater and earlier than in normoreactive MI. The connection of MG, CK, and ASAT changes with reactivity allows them to be used in prognosticating MI healing. PMID- 1625921 TI - [Effect of the antioxidant ionol on myocardial energy metabolism and the course of traumatic shock]. AB - Energy metabolism was studied in experiments on rats with due regard for the individual features of the organism's reaction to trauma. The animals were divided into 2 subgroups according to the survival period during the experiment. Disorders of mitochondrial function were revealed in both subgroups, but they differed in degree according to the severity of the process. Preliminary injection of the antioxidant ionol prolonged the animals' survival and prevented disorders of mitochondrial function. The article discusses the possibility of preventing activation of free-radical oxidation of the membrane lipids and removal of their damaging effect on the mitochondria with ionol. PMID- 1625922 TI - [Role of changes in insulin-binding activity and energy metabolism in the pathogenesis of experimental crush syndrome]. AB - Study of the effect of the crush syndrome on cell metabolism and insulin-binding activity revealed a new aspect of the pathogenesis of the syndrome, namely, a marked reaction of the mononuclear receptor apparatus. Accumulation of lactate in the tissues and the development of acidosis probably play an important role in disturbance of the insulin-binding activity of the plasma membrane. Reduction of the level of tree adenine nucleotides and ATP in particular may be of essential importance in the late stages of compression. Of importance in the pathogenesis of the crush syndrome was the binding of insulin with its receptors and the subsequent intensification of metabolic disorders and reduction of phosphorylation, which in turn may be the cause of reduced transmission of the signal to the receptors, i. e. disorder of the postreceptor action of insulin. PMID- 1625923 TI - [Effect of staphylococcal toxin on the microcirculatory system]. AB - Study of microcirculation in the mesentery of narcotized rats showed that the staphylococcal toxin causes increased migration of leukocytes, aggregation of formed elements, and disturbance of the blood flow in the small venules and arterioles. The toxin stimulates rhythmic contractile activity of the lymphatic microvessels and induces their constriction and even complete obliteration. The lymphoconstrictive effect of the toxin is weakened by verapamil and completely removed by dimethyl sulfoxide. PMID- 1625924 TI - [Protective effect of unithiol and its combination with magnesium sulfate in endotoxin poisoning and in infection by gram-negative bacteria]. AB - It is shown that unithiol protects mice from death in intoxication by S. typhimurium and S. Sonnei lysates and in infection caused by S. typhimurium. Magnesium sulfate strengthens the protective effect of unithiol. It is suggested that the protective effect of unithiol is due to its antioxidant action. PMID- 1625925 TI - [Use of enterosorption for reducing the biogenic amine content of blood and exudate in peritonitis]. AB - The administration of an enterosorbent prevents increase of the level of biologically active substances in blood and exudate of rats in fecal peritonitis. The results of biochemical and radionuclide methods of examination allow 2 mechanisms of reduction of the histamine and serotonin level in blood and exudate to be distinguished--direct and mediated. PMID- 1625926 TI - [Use of superoxide dismutase in infusion therapy of experimental hemorrhagic shock]. AB - The work deals with study of the possibility of increasing the efficacy of infusion therapy in massive blood loss by preliminary administration of superoxide dismutase (SOD). The data obtained bear evidence that in preliminary administration of SOD infusion of a blood substitute produces a more marked and stable improvement of central hemodynamics and microcirculation, oxygen regimen, and acid-base equilibrium in rats. A significant increase of the circulation volume and stroke volume of the heart following SOD injection may be linked with lesser intensity of lipid peroxidation in the cardiocyte membranes during reoxygenation. PMID- 1625927 TI - [Modulating action of intermediate molecular weight peptides on the course of experimental burn injury]. AB - Preliminary injection of middle mass peptides (MMP) obtained from blood of intact dogs and dogs with burn injury aggravated the response of mice and rats to thermal injury. The mortality among mice with burns grew and the reaction of the lymphoid organs (thymus and spleen) of rats to the thermal burn was intensified. The aggravating action of MMP in mice correlated well with their damaging effect in experiments on human blood neutrophils. A MMP fraction possessing a protecting effect in burns in rats was isolated from the blood of intact dogs. The data obtained are discussed from the standpoint of the pathogenetic importance of MMP in burn disease. PMID- 1625928 TI - [Effect of alpha1-acid glycoprotein on rheologic blood parameters in experimental thermal burns]. AB - Experiments were conducted on albino noninbred mice and rats to study the effect of alpha 1-acid glycoprotein (alpha 1-AG) on burn healing. Injection of alpha 1 AG in the first 24 hours after the burn causes rapid epithelialization and increases contracture of the burn wounds. At the same time it increases the deformity of the red cells, reduces their hemolysis due to a mechanical effect, and reduces spontaneous aggregation of blood platelets. No authentic effect of alpha 1-AG on the aggregation of red cells was revealed. It is suggested that alpha 1-AG is a natural defence factor of the organism which prevents the development of microvascular thrombosis and limits in this way the size of the inflammatory and necrotic processes. PMID- 1625929 TI - [Immunotropic activity of human alpha1-glucoprotein]. AB - Experiments were conducted to study the effect of alpha-acid glycoprotein on a fatal infection caused by Pseudomonas pyocyanea, growth of melanoma B-16, and transplantation of a skin graft from C57BL/6 mice to CBA mice. Injection of the agent significantly increased the anti-infection resistance in mice, suppressed growth of melanoma-16, and prolonged the survival of the skin grafts, which was evidence of marked glycoprotein immunomodulating activity. PMID- 1625930 TI - [Functional state of immunocompetent cells in rabbits partially tolerant to lipopolysaccharide]. AB - The author studied the regular features of interleukin-1 (IL-1) formation and proliferative activity of cells of the lymphoid organs in rabbits tolerant to lipopolysaccharide (LPS). A weak temperature response of LPS tolerant rabbits to LPS administration was linked with decrease of IL-1 secretion by blood and splenic cells and the formation in the spleen of a cell population which had a suppressive effect on IL-1 production. In administration of large LPS doses, the changes of the processes of IL-1 proliferation and production in the various lymphoid organs of the rabbits differed. The proliferative response of the splenic cells to T- and B-cell mitogens reduced, a tendency to intensification of the proliferative processes was noted in the thymus. The secretion and accumulation of IL-1 by blood and splenic cells was reduced, the secretion and intracellular content of this mediator in the thymus and lymph nodes was increased. PMID- 1625931 TI - [Blood cyclic nucleotide content in acute regional ischemia of the extremities]. AB - Fifty healthy males aged from 19 to 34 years were examined. Experiments were conducted on 30 male mice weighing 200-250 g. After 10- and 20-minute ischemia of the upper limb the concentration of cAMP and cGMP in its venous blood increases in direct proportion to the duration of ischemia. Increase of the level of cyclic nucleotides (CN) in the blood does not depend on hypersecretion of catecholamines. Increase of the CN level coincides in time with increase of blood CPK. The mechanisms of changes in the blood CN level in ischemia are discussed. PMID- 1625932 TI - [Study of contractile properties of muscles of curarized animals by the method of stimulation impedancography]. AB - The effect of relaxation doses of tubocurarine on the stimulation and contractile properties of muscles in complete synaptic block was studied in experiments on laboratory rats by means of a previously developed method of stimulation impedancography. During intramuscular electrostimulation the stimulus threshold for short 0.01 mc test impulses increased, while the steepness of the characteristic "force of action--contractile effect" curve, registered at 1 mc impulses, reduced. The reduction was caused by loss of the function of synaptic nerve structures which take part in recruiting the contractile elements. Nonsynaptic mechanisms of recruiting through direct stimulation of the muscle fibres ensure 45% of recruitment. Changes of the duration of the contraction were not detected in the first 20 minutes of the effect. After 60-80 minutes of relaxation there was a tendency to prolongation of the time of the contraction act, which may be caused by prolonged immobilization of the animals. PMID- 1625933 TI - [Effect of blood coagulation on adenylate nucleotide metabolism of erythrocytes in healthy people]. PMID- 1625934 TI - [Mechanism of changes in renal functions in osmotic irritation of the right atrium]. AB - Chronic experiments conducted on 17 dogs whose ureters were brought out on the skin of the abdomen showed that administration of solutions of saccharose (1150 mmol/l) and NaCl (515 mmol/l) into the right atrium reduces diuresis and increases natriuresis. The concentration of atrial natriuretic factor in the blood does not change, vasopressin and cortisol secretion increases while that of aldosterone decreases. It is concluded that, in addition to the cardiopeptide mechanism regulating the blood volume, the right atrium possesses a reflex osmoregulatory mechanism. PMID- 1625935 TI - [Effect of cultured Polyscias cells on the activity of components of the protein synthesizing system of rabbit liver]. AB - The authors studied teh effect of cultured Polyscias filcifolia Bailey cells on protein biosynthesis in an acellular system obtained from the liver of rabbits in experimental myocardial ischemia. It was found that the preparation normalizes the values of protein biosynthesis, the duration of the average polypeptide chain synthesis, and the activity of aminoacyl-tRNA synthetases. PMID- 1625936 TI - [Disease as pathology of the information process]. PMID- 1625937 TI - [Construction of histograms of time intervals without conducting linear measurements]. PMID- 1625938 TI - [Glucocorticoid dependence as a consequence of inadequate conditions in engagement of one adaptational mechanism of the immune system]. PMID- 1625939 TI - [Glucose consumption by the rat brain in ethanol intoxication and the abstinence syndrome]. AB - The effect of acute and chronic alcohol intoxication and of the syndrome of ethanol withdrawal on the consumption of glucose by the brain of rats was studied by means of intravascular ethanol infusion. Infusion of ethanol into the internal carotid artery had no effect on glucose consumption by the brain, while its infusion into the femoral vein reduced consumption twofold. The effect was completely removed by the inhibitor of alcohol dehydrogenase pyrazole. Chronic intoxication also caused a twofold decrease of glucose utilization by the brain of rats. Infusion of ethanol into the internal carotid artery of rats who were in a state of alcoholic intoxication led to increase of glucose consumption by the brain to the control level. Infusion of ethanol into the femoral vein in this case had no effect on glucose consumption by the rat brain. Utilization of glucose by the brain diminished to an equal degree in rats suffering from the syndrome of ethanol withdrawal and in animals who were in a state of alcoholic intoxication. Infusion of ethanol, both intraarterial and intravenous, had no effect on glucose consumption by the brain. Activation and inhibition of the function of external respiration were encountered in equal concentrations of ethanol in blood flowing from the brain, whatever the method of its infusion. PMID- 1625941 TI - Editorial ethics. PMID- 1625940 TI - Antibiotic treatment failures in acute otitis media. PMID- 1625942 TI - Introduction and overview: why another polemic on ethics? PMID- 1625943 TI - The ethical practice of pediatrics in a world of potential conflicts: an interview. Interview by John M. Freeman. PMID- 1625944 TI - On paternalism. PMID- 1625945 TI - Advocating for the abused child: can ethics and the law be in conflict?. Interview by John M. Freeman. PMID- 1625946 TI - When too much is not enough. PMID- 1625947 TI - Federal efforts through an office of adolescent health. PMID- 1625948 TI - Neonatal petechiae: strategies for nursing interventions. AB - Planning appropriate nursing care for the neonate with petechiae requires knowledge of its etiology, accurate assessment, and ongoing monitoring. The nurse can use this information to provide interventions that facilitate healing, prevent further sequela, and enhance parental involvement and interaction in the care of their newborn. PMID- 1625950 TI - Chronic granulomatous diseases of childhood. AB - Nursing care for the child with chronic granulomatous disease (CGD) is complex and challenging. Understanding the mechanism behind the disease increases the effectiveness of nursing care. PMID- 1625949 TI - Special children, special needs: the ectodermal dysplasias. AB - Ectodermal dysplasias are a group of genetic disorders that arise from abnormalities of the ectoderm. Children with the disorder exhibit a wide range of clinical features that frequently affect the skin, teeth, hair, and sweat glands. With early detection and careful management, these children can lead normal, productive lives. PMID- 1625951 TI - Care of the infant in a Pavlik harness. AB - Congenital hip dysplasias, a common orthopaedic problem in children, can be treated effectively if diagnosed early. One such valuable tool in treating this disorder is the Pavlik Harness. These authors describe their child's experience with the Pavlik Harness along with the personal needs of the child and family. PMID- 1625952 TI - Childhood injuries: an epidemiologic approach. AB - Injuries are the leading cause of childhood death and disability in the United States today. However, injuries can be studied, their magnitude described, and risk factors identified. Furthermore, many injuries can be prevented and controlled with available knowledge and technology. PMID- 1625953 TI - Munchausen syndrome by proxy: recognizing the victim. AB - Munchausen syndrome by proxy is a serious and potentially lethal form of child abuse in which a parent deliberately induces or reports physical symptoms in a child. The child not only suffers from parent's action, but he or she is subjected to an extensive battery of invasive medical and radiological testing that are unnecessary and painful. All health care professionals must work together to ensure that the syndrome is discovered in time and the child is protected. The child's psychological and physiological welfare are in danger. PMID- 1625954 TI - Practices surrounding ribavirin administration. AB - Fifty major pediatric medical centers were queried regarding their practice surrounding Ribavirin administration. The survey addressed safety precautions and prescriptive practices. The object of the survey was to assist community hospitals in policy development for Ribavirin use. PMID- 1625955 TI - Pediatric management problems. Tummy ache. PMID- 1625956 TI - Role of carnitine supplementation in pediatric patients receiving valproic acid therapy. PMID- 1625957 TI - Extubation and reintubation in the NICU: identifying opportunities to improve care. AB - An investigation was conducted to determine the overall incidence and reasons for extubation and reintubation in a NICU population in order to establish a baseline for ongoing quality assessment and evaluation monitoring. The investigators sought to identify factors associated with accidental extubation for which action plans to improve care could be developed. PMID- 1625958 TI - Terminal care costs in childhood cancer. AB - PURPOSE: To present a conceptualization of health care costs and to describe costs of health care in the terminal phase of childhood cancer. To present an exploratory comparison of the costs of terminal care in the hospital versus home care services, and to discuss the use of cost research in nursing practice. METHOD: Telephone interviews were done approximately 16 months after the death of a child to retrospectively ascertain services used, costs to the family, and insurance information. Provider billing and insurance data were subsequently collected. The families were divided into two groups based upon the use of home care or traditional hospital care during the terminal phase. FINDINGS: Home care was less expensive for total costs than hospital care. Home care was more expensive for nonhealth care and indirect costs than hospital care. CONCLUSIONS: Nurses should consider direct health care costs, nondirect health care costs, and indirect costs when assisting family decisions about care. Nurses and families should be aware of potential cost shifting. PMID- 1625959 TI - Adolescent health: the need for stronger governmental policies. PMID- 1625960 TI - Health promotion, health protection, and disease prevention in childhood. AB - Approximately one-half of America's youth are at risk for developing cardiovascular disease as adults. Because the etiology of adult cardiovascular disease is multifactorial, a number of interventions have been designed to lessen this health risk. Health promotion strategies to reduce cardiovascular disease focus on teaching children and adolescents healthy lifestyle habits (regular exercise, prudent eating, abstinence from tobacco). Health protection strategies include requiring food labels that contain information about fat and sodium content and publishing warnings about the hazards of tobacco use. Disease prevention strategies encompass clinical counseling regarding control of blood pressure and weight. This article highlights some of the existing pediatric health promotion/health protection/disease prevention programs aimed at reducing adult cardiovascular disease. PMID- 1625961 TI - Private practice: the time is now. AB - Nurses are creative professionals who have their own expertise in delivering personalized health care. Until we establish our own autonomy within the health care system, we will continue to be misjudged and undervalued. The development of an independent nursing practice is one method of demonstrating autonomy. What is needed is proper information, positive thinking and the courage to move forward. We need to support nurses in the pursuit of autonomy for the sake of ourselves, our clients, and the health care system. PMID- 1625962 TI - Developmental assessment of the technology-dependent infant and young child. AB - Appropriate developmental intervention for the technology-dependent infant or young child has its basis in a carefully designed and thorough assessment. The role of the nurse is central in this process. This article guides the nurse through an analysis of developmentally relevant medical considerations, an examination of tolerance and endurance, the determination of developmental level, an approach to working with families, and the process of translating assessment data into intervention plans. PMID- 1625964 TI - Professional development module. P9: Advocacy. Part (ii): The 'how' of advocacy. PMID- 1625963 TI - Primary prevention of childhood lead poisoning: a goal for the 1990s. AB - Childhood lead poisoning remains a common problem in America today. The U.S. Department of Health and Human Resources has recently released a strategic plan on eliminating childhood lead poisoning, and health care professionals should become familiar with the basic elements of the plan. PMID- 1625965 TI - Better training and resources needed for resuscitation. PMID- 1625967 TI - Swingeing London. PMID- 1625966 TI - Outreaching. PMID- 1625968 TI - Changing behaviour. PMID- 1625969 TI - Springboard to success. PMID- 1625970 TI - Impractical project. PMID- 1625971 TI - Let's tell it as it is. PMID- 1625972 TI - Teenage traumas. PMID- 1625973 TI - Lump it or like it. PMID- 1625974 TI - Education--super confusion. PMID- 1625975 TI - Living with loss. PMID- 1625976 TI - Making sense of the principles of genetics. PMID- 1625977 TI - Show some emotion. PMID- 1625978 TI - Learning to fail. PMID- 1625979 TI - Can you hear me? PMID- 1625980 TI - Island of strength. PMID- 1625982 TI - Minister will not change law on HIV. PMID- 1625981 TI - Trusting to technology. PMID- 1625983 TI - Improving lines of communication. PMID- 1625984 TI - Choosing garments to aid incontinence. PMID- 1625985 TI - A matter of life and death. PMID- 1625986 TI - An approach to minor trauma. PMID- 1625987 TI - Preparing to heal. PMID- 1625988 TI - High HIV toll on children. PMID- 1625990 TI - S-100 positive undifferentiated neuroblastomas with a special reference to the tumor stroma related to favorable prognosis. AB - Fifty-four cases of undifferentiated neuroblastoma (stroma-poor neuroblastoma with undifferentiated histology) were studied immunohistochemically for the presence of S-100 protein-positive cells and extracellular matrix proteins (laminin, type IV collagen and fibronectin). In 30 of the 54 patients, the tumor had S-100 protein-positive cells in the peculiar stroma observed as thick fibrocellular septa (trabecular pattern) or delicate fibrovascular meshwork surrounding small nests of tumor cells (reticular pattern). The tumors were divided into four subgroups according to the stromal patterns: type A showing a predominant "reticular" pattern (14 cases); type B showing a predominant "trabecular" pattern (6 cases); type C showing both "reticular" and "trabecular" patterns (14 cases), and type D lacking either pattern but rich in vascular channels (20 cases). Clinicopathologically, the patients with S-100 protein positive cells had a more favorable outcome (86.7% 2-year survival rate) than patients without these cells (12.0% 2-year survival rate). It is concluded that the existence of peculiar fibrovascular stroma containing S-100 protein-positive cells and extracellular matrix proteins is correlated with a favorable prognosis in undifferentiated neuroblastomas. PMID- 1625989 TI - Immunohistochemical analysis of ras oncogene p21 product in human gastric carcinomas and their adjacent mucosas. AB - In an attempt to clarify the relationship between ras oncogene expression and the clinico-pathological features of malignant and pre-malignant lesions of the stomach we undertook the immunohistochemical study of the expression of ras gene p21 product in a series of eighty gastric carcinomas and their respective adjacent mucosas. In two cases the mRNA of Ha-ras was also studied by in situ hybridization. The majority of gastric carcinomas as well as their adjacent non neoplastic mucosas expressed ras gene product. There was a significant relationship between the expression of ras gene p21 product and the morphologic pattern of the tumours. An enhanced ras expression was found in several conditions regarded as precursor lesions of intestinal and/or diffuse types of gastric carcinoma (dysplasia, foveolar hyperplasia and even the neck zone of normal-appearing gastric glands, namely in the mucosa adjacent to diffuse carcinomas). Ras expression was actually more prominent in most of these conditions than in their respective adjacent carcinomas. No significant relationship was found between ras expression and invasiveness of the wall, nodal metastases and venous invasion. PMID- 1625991 TI - Helix pomatia lectin binding pattern of brain metastases originating from breast cancers. AB - The glycosylation pattern of brain metastases originating from primary breast carcinomas was investigated using Helix pomatia agglutinin (HPA), a lectin which recognises N-acetyl-galactosamine (GalNac) residues of glycoconjugates. In a previous retrospective study this lectin was shown to label only those primary breast cancers that metastasised. To explore this as a clinical marker of metastatic breast cancer behaviour it is necessary to analyse the HPA binding pattern of metastases to see if this differs from primary cancers. To test the question if brain metastases commitently retain this trait of metastatic primary tumors, we studied Helix pomatia binding pattern of brain metastases removed by surgical excision and immediately fixed and processed. Brain metastases from 16 patients with breast cancer were obtained, 13/16 metastases showed binding to the cytoplasm in the majority of cancer cells, 3/16 did not show binding to cancer cells. Normal adjacent brain showed binding to red blood cells, to capillary endothelium of several biopsies and to rare neurones; this binding did not relate to cancer cell binding. Therefore we conclude that HPA is a relatively stable marker for metastasizing breast cancer cells. PMID- 1625992 TI - Cushing syndrome-associated pheochromocytoma and adrenal carcinoma. An immunohistological investigation. AB - Seven adrenal carcinomas and seventeen pheochromocytomas (PHs), two of which were clinically associated with a Cushing's syndrome and one associated with multiple endocrine neoplasia Type II (MEN-II), were investigated immunohistologically with a panel of antibodies against intermediate filament proteins, a proliferation associated nuclear antigen (Ki-67), neuroendocrine tumor markers, and different hormones on paraffin-embedded tissue sections and, from 19 cases, also on frozen tissue sections. Synaptophysin proved to be the most reliable tumor cell marker on both snap-frozen and paraffin-embedded tissue but, like antibodies against NSE, yielded unspecific stainings in the carcinomas. The two Cushing-associated pheochromocytomas (CaPH) showed the same immunohistological profile as the other PHs, except one chromogranin-negative tumor. Five PHs showed weak reactivity for calcitonin, one for serotonin, and two for a-HCG in small amounts. All PHs lacked other hormone expression, including ACTH. The average growth fraction was small (2.2%) in 13 cases, but 80% of the tumor cells were proliferating in one case of CaPH. Adrenal carcinomas showed only weak or no expression of keratin in one case, a homogenous or droplet, non-filamentous cytoplasmic staining with antibodies against neurofilament in frozen tissue section, and they were completely chromogranin-negative. The average growth fraction was 7.6% in 5 cases. PMID- 1625993 TI - Prolactin-containing pituitary adenomas. Their characteristics and comparative study with non-prolactin adenomas. AB - Immunohistochemical study of 130 pituitary adenomas shows that 31% are prolactin containing adenomas, two-thirds of which are monohormonal adenomas, i.e. prolactin cell adenoma, and one-third are multihormonal adenomas, i.e. mixed growth hormone cell-prolactin cell adenoma and plurihormonal adenoma with prolactin. Clinical symptoms including amenorrhea and galactorrhea are not useful in distinguishing prolactin from non-prolactin adenomas. Serum prolactin concentration of 80 ng/ml is a good cut-off point to distinguish prolactin cell adenoma from non-prolactin adenoma but can not separate many of the multihormonal adenomas from non-prolactin adenomas. Calcification is not only more commonly seen but also more prominent in prolactin-containing adenomas. Spheroid amyloid is present in one prolactin cell adenoma. Immunohistochemistry is specific and reliable in identifying prolactin-containing adenomas. All prolactin cell adenomas and 2/13 multihormonal adenomas show paranuclear staining of prolactin in almost every adenoma cell. The remaining (11/13) multihormonal adenomas show less prolactin cells and diffuse cytoplasmic staining of prolactin. The prolactin staining pattern in the latter group is unique and appears to be indicative of the presence of other hormone(s). PMID- 1625994 TI - Immunohistochemical study of the inflammatory infiltrate in villitis of unknown etiology. A qualitative and quantitative analysis. AB - Villitis is characterized by an inflammatory infiltrate within the substance of the chorionic villi. Quantitative and qualitative analyses of the mononuclear infiltrate in areas of villitis were performed in placentas with villitis of unknown etiology (VUE). We used a panel of monoclonal antibodies and immunoperoxidase technique in paraffin sections from 17 placentas with VUE and 8 without VUE. Macrophages followed by T lymphocytes were the predominant inflammatory cells in areas of villitis in virtually all cases. B lymphocytes were not observed and monocytes were present usually in small number in 58 per cent of the cases. Mononuclear cells which expressed HLA-DR antigens were found in 75 per cent of the cases. In areas of villitis with trophoblastic necrosis, we found monocytes and some T lymphocytes adhered to them. These cells apparently had migrated from the maternal circulation. We suggest that in areas of villitis with destruction of the trophoblast and its basal membrane the inflammatory infiltrate might have a mixture of fetal and maternal cells. The maternal monocytes and T lymphocytes might be attracted to these sites of trophoblastic necrosis and activated due to exposure to fetal MHC antigens of the villous stroma. PMID- 1625995 TI - Ultrastructure of Warthin-Starry stain-positive bacteria in abscess-forming reticular lymphadenitis. AB - This study describes the ultrastructure of Warthin-Starry (WS) stain-positive bacteria in abscess-forming reticular lymphadenitis (ARL) compatible with cat scratch disease (CSD). Sections containing WS-positive bacteria were re-embedded in Epon, and semithin sections were examined by electron microscopy. Silver particles were aggregated on the outer surfaces of the bacteria. Stereoscopic observations clearly showed that the bacteria were pleomorphic, rod-shaped, arranged in a row or at an angle, and frequently showed septal formation. Electron microscopy of ultrathin sections revealed that the cell wall possessed an outer membrane characteristic of gram-negative bacteria. The results indicate that rod-shaped bacteria with the WS-positive, gram-negative staining cause ARL histopathologically consistent with CSD. PMID- 1625996 TI - Cylindrical cell papilloma of the nasal cavity and paranasal sinuses. A histochemical and cytochemical study. AB - A cylindrical cell papilloma occurring in the sino-nasal mucosa of a 61-year-old woman was studied histochemically at both light and electron microscopic levels. The cylindrical cells demonstrated distended intracytoplasmic microcysts with numerous microvillous projections on the apical cell membrane. The retained mucosubstance in the cystic spaces stained intensely with HID-TCH-SP sequence and showed no apparent communication with the extracellular space. These findings indicate that the cylindrical cells may be of mucous-secreting cell derivation, being derived from cells possessing abnormal and/or failed secretory function. The property of sulfated mucin in the 'cylindric' intracytoplasmic cysts is suggested to be the result of endodermal displacement or metaplasia of the Schneiderian epithelium. PMID- 1625997 TI - Cell kinetics of melanocytes in common and dysplastic nevi and in primary and metastatic cutaneous melanoma. AB - The 3H-thymidine labelling (LI) and mitotic (MI) indexes were calculated in 29 cutaneous melanocytic lesions: 6 common nevi (CN), 11 dysplastic nevi, subclassified as nevi with architectural atypia (NAA = 4) and nevi with cyto architectural atypia (NCAA = 7), 2 melanomas in situ (MIS), 4 invasive superficial spreading melanomas (IM) and 6 metastatic melanomas (MM). The LI mean values resulted to be: CN = 0.23%, NAA = 0.98%, NCAA = 1.79%, MIS = 5.75%, IM = 5.16%, MM = 3.80%. In CN, NAA, NCAA and MIS, these values were calculated at epidermal level; in IM and MM at dermal level. At dermal level, the LI mean values of CN, NAA and NCAA were: 0.20%, 0.20%, 0.23% respectively. The MI mean value was close to 0 in CN, NAA, NCAA, MIS; 0.18% in IM, 0.16% in MM. Confirming a low proliferative activity in CN and a high activity in melanomas (MIS, IM, MM), the results showed that dysplastic nevi (NAA, NCAA) had a proliferative activity intermediate between common nevi and melanomas. The lesions with melanocytic atypia (NCAA) resulted to have a higher proliferative activity than those without this histological feature (NAA). PMID- 1625998 TI - Statistical evaluation of the predictive power of fine needle aspiration (FNA) of salivary glands. Results and cytohistological correlation. AB - Fine needle aspiration (FNA) of the salivary glands was carried out on 97 patients. Diagnosis was confirmed by histological findings in 93 patients. There were 75 benign lesions (including 52 benign tumours) and 18 malignant lesions. In our series "positive predictive value" of FNA was 0.900 and the negative predictive value was 0.963. Thus, the probability of a false positive is 0.100 and of a false negative 0.037. PMID- 1625999 TI - Subsequently occurring leiomyosarcoma and desmoid tumor of the right thigh. AB - We present the case of a 44-year-old patient with a primary leiomyosarcoma of the right upper thigh, who developed a second mesenchymal lesion at the same thigh, diagnosed as an extra-abdominal desmoid tumor, some months after surgical treatment of his leiomyosarcoma. Clinically, histomorphologically, DNA cytometrically, immunohistochemically and radiologically the different histogenetic origin of the two lesions could be proven. The patient died 17 months after his first tumor diagnosis of lung metastases of his leiomyosarcoma. PMID- 1626000 TI - Diffuse bilateral glomerulocystic disease of the kidneys and multiple cardiac rhabdomyomas in a newborn. Relationship with tuberous sclerosis and review of the literature. AB - A case of glomerulocystic disease of the kidneys in a newborn is described. The kidneys were very large and diffusely cystic. Histologically, all portions of the nephron were involved and some of the cysts were lined by a prominent hyperplastic eosinophilic epithelium. This, together with the presence of numerous cardiac rhabdomyomas, a nodular haemangiomatous harmartoma and histiocytoid cell nests in the spleen were strongly suggestive of tuberous sclerosis. The relation between glomerulocystic kidney disease and tuberous sclerosis is discussed. PMID- 1626001 TI - Primary pure choriocarcinoma of the liver. AB - We report a pure choriocarcinoma of the liver studied at necropsy. The tumour was diagnosed ante-mortem and treated by chemotherapy with no satisfactory response. Previous cases of hepatic choriocarcinoma are reviewed and criteria to diagnose this extragonadal neoplasm are recommended. PMID- 1626003 TI - A rare and special privilege. PMID- 1626002 TI - Peliosis lienis: uncommon cause of rupture of the spleen. AB - Rare anomaly: peliosis lienis, which was found in the spleen of a woman splenectomised for rupture, is presented. Speculations on the etio-pathogenesis of this peculiar disorder are discussed based on literary data. The awareness of this pathological curiosity may be of practical importance because of the hazard of life-threatening haemorrhagic consequences following rupture of the lesions. PMID- 1626004 TI - On consulting and being consulted. PMID- 1626005 TI - The pediatric hospital consultant. PMID- 1626006 TI - Eye injury. PMID- 1626007 TI - Henoch-Schoenlein purpura. PMID- 1626008 TI - Prenatal diagnosis and carrier detection by DNA analysis. PMID- 1626009 TI - Children, adolescents, and television. PMID- 1626010 TI - Cutaneous fungus infections in children. PMID- 1626011 TI - Let the change come from within. The process of change in nursing. AB - Current developments in nurse management and education have resulted in significant changes to nursing practice. By planning ahead and acting as change agents, nurses can seize the initiative to apply change in a positive way. PMID- 1626012 TI - Assessment allows action on risk factors. Infection control and surgical wounds. AB - Surgical wound infection is costly to the NHS and debilitating to the patient. Thorough assessment of patients' risk of developing infection allows nurses to act to reduce that risk. PMID- 1626013 TI - On course for an enhanced career? An assessment of the diploma in nursing. AB - The Diploma in Nursing is designed to improve nursing practice and enhance job promotion, but is this true in practice? A research project asked nurses who had completed the diploma whether they and their practice had benefited from the course. PMID- 1626014 TI - An unfinished story. Helping people to come to terms with miscarriage. AB - The pain and distress caused by miscarriage is often underestimated. By offering information, counselling and advice, nurses and midwives can help couples come to terms with their loss and face the future with greater confidence. PMID- 1626015 TI - When self-help begins at home. Pain control in cancer care. AB - Ineffective pain control prevents many people with advanced cancer from being cared for at home as they would wish. Teaching patients about their analgesia and encouraging the use of complementary techniques can help prevent unnecessary suffering. PMID- 1626016 TI - Thalassaemia: a preventable disease? PMID- 1626017 TI - Searching for signs of revival. Uses and abuses of the Glasgow coma scale. AB - The Glasgow coma scale is widely used to measure patients' levels of consciousness. Attention to detail and an understanding of the scale's assessment criteria are essential to avoid misuse. PMID- 1626018 TI - Malignant melanoma: mole watching and the adolescent. PMID- 1626019 TI - A valuable contribution to care. The role of leg ulcer resource groups. AB - The survey on which this series has been based suggests district nurses are becoming more competent and confident in treating most leg ulcers. This final article discusses possible future research and the role of leg ulcer resource groups. PMID- 1626020 TI - On a donor run. PMID- 1626021 TI - Determination of optical properties of turbid media using pulsed photothermal radiometry. AB - Pulsed photothermal radiometry (PPTR) measures blackbody radiation emitted by a sample after absorption of an optical pulse. Three techniques for obtaining the absorption coefficient of absorbing-only, semi-infinite samples are examined and shown to give comparable results. An analytic theory for the time dependence of the PPTR signal in semi-infinite scattering and absorbing media has been derived and tested in a series of controlled gel phantoms. This theory, based on the diffusion approximation of the radiative transport equation, is shown to model the time course of the detected signal accurately. Furthermore, when the incident fluence is known, the theory can be used in a non-linear, two-parameter fitting algorithm to determine the absorption and reduced scattering coefficients of a turbid sample with an accuracy of 10-15% for transport albedos ranging from 0.42 0.88. PMID- 1626022 TI - Analysis of tissue optical coefficients using an approximate equation valid for comparable absorption and scattering. AB - New photosensitizers activated by longer wavelengths than 630 nm light used with Photofrin II are under evaluation by various groups for the treatment of malignancies. Any increase in tumour volume destroyed by these agents as compared to Photofrin II will be partly determined by tissue penetrance at the longer wavelengths. Attenuation coefficients were measured for various tissues at 630 nm and the more penetrative near infrared wavelength of 789 nm. A new model of light propagation in tissue is shown to be accurate for arbitrary ratios of absorption and scattering, by comparison with a rigorous solution to the transport equation. Absorption and transport scattering coefficients of tissues at 630 and 789 nm were obtained by fitting this model to optical attenuation measurements. In vitro tissues included bovine heart, kidney and tongue, pig liver and fat, and chicken muscle; in vivo tissues included Dunning R3327-AT and R3327-H tumours. The penetration depth was found to be 1.35-2.25 times greater at 789 than 630 nm, depending on tissue type. The greatest differences in penetration between the two wavelengths were in the highly pigmented tissues. These substantial increases in penetration in the infrared may be important in future applications of photodynamic therapy. PMID- 1626023 TI - Mathematical modelling of objectives in radiation therapy treatment planning. AB - We view radiation therapy treatment planning (RTTP) as a problem of constrained optimization. In this context, the 'optimal' treatment is one that maximizes some objective function subject to the inherent constraints of the problem. We discuss two objective functions which are motivated by biological considerations rather than mathematical expedience. One of these measures the 'goodness' of a treatment in terms of its probability of success. The other measures the degree to which a treatment succeeds in satisfying a system of constraints that are mutually contradictory. We describe how to actually perform the optimization of these objective functions in practice and show some numerical results which demonstrate advantages of these objective functions over their more conventional counterparts. PMID- 1626024 TI - Analogous filters for beam shaping in diagnostic radiology. AB - A computer simulation based on photon transport calculation was used to evaluate the properties of a wide variety of materials that could be used for the filtration of x-ray beams. A single filter was added to the inherent filtration. For comparison, the concept of analogous filters was introduced: two filters were considered analogous if both produced the same ratio of entrance exposure at the patient to the energy absorbed in the detector consisting of a pair of intensifying screens positioned immediately behind the water phantom. The efficiency, contrast and integral dose were calculated for filters of odd atomic numbers from 1 to 91 with a large number of different parameters (48,600 different combinations). They include essentially all major diagnostic radiology procedures, except mammography. Only extreme cases are presented here. No magic filter was found which would produce increased contrasts or a decreased integral dose, while maintaining efficiency close to that of aluminium. Filters of some atomic numbers produced increased contrast, but had negligible efficiency. Analogous filters of atomic numbers between 7 and 37 and also between 71 and 91, had almost identical properties but varied efficiencies. Unpredictable behaviour was obtained with filters of atomic numbers 38 to 70, where small changes in atomic number may produce large changes in all the properties due to the presence of K-edge discontinuities. PMID- 1626025 TI - Temperature uniformity during hyperthermia: the impact of large vessels. AB - During hyperthermia the presence of a large vessel entering the heated volume and carrying blood at the systemic temperature can be an important source of temperature non-uniformity and possible underdosage. The minimal tumour temperature near a large vessel is determined by the vessel wall temperature: a number of factors influencing the vessel wall temperature are considered- effective tissue conductivity, flow type, vessel size, entrance effects and counter-current flow. In some specific cases, especially when tissue perfusion is high, the vessel wall temperature may reach therapeutic levels when the mean blood temperature is still low. In general, well perfused tumours have a better chance of being heated uniformly. Regional heating improves temperature uniformity by reducing entrance and equilibration effects as blood is heated before entering the tumour. Raising the core temperature also reduces temperature inhomogeneity. Spatial SAR resolution should preferably be of the order of magnitude of a centimetre or better. PMID- 1626026 TI - Bone composition measured by x-ray scattering. AB - Ten composite samples consisting of cortical bone and adipose tissue, in known proportions, were made. The intensity of monochromatic x-rays (energy 8 keV) scattered by these samples was determined as a function of the modulus of the scattering vector, K. The ratio of the heights of peaks at K values of around 134 and 22 nm-1 provided a measure of the ratio of adipose tissue to bone mineral in these samples. This method was then used to determine the ratio of adipose tissue to mineral in samples of trabecular bone from 16 vertebral bodies. The results were correlated with measurements of the bone composition determined by ashing (r = 0.66) and histomorphometry (r = 0.66). Furthermore, the ashing and histomorphometry results were correlated with each other (r = 0.68). The feasibility of using higher energy x-rays (35-80 keV) for obtaining the same information from bone within the body is briefly discussed. PMID- 1626027 TI - Measurement of iron bioavailability by means of stable 54Fe and mass spectrometry. AB - Stable isotopes represent a useful tool for the assessment of biokinetic parameters in in vivo studies on humans. A procedure is described to evaluate the bioavailability of iron in pharmaceutical preparations by means of 54Fe as a tracer and mass spectrometry for the determination of time dependent changes in the isotope ratio of 54Fe/56Fe in red blood cells. Iron tablets with an increased portion of 54Fe were administered to iron deficient subjects and red cell iron utilization was used as a measure of iron bioavailability. Iron utilization was derived from changes in the 54Fe/56Fe ratio as evaluated by means of fast atom bombardment-mass spectrometry (FAB-MS) on processed blood samples. A good intraindividual reproducibility was observed for blood samples drawn at various times after application of the trial drug. Figures for bioavailability and its interindividual variations were in the range expected from comparable studies on similar iron preparations using radioiron as tracers. The results obtained show that quantitative data of bioavailability from pharmaceutical iron preparations may be obtained without radiation exposure of the subjects investigated. PMID- 1626028 TI - The automatic computer detection of subtle calcifications in radiographically dense breasts. PMID- 1626029 TI - The use of a radiation sensitive CCD camera system to measure bone mineral content in the neonatal forearm: a feasibility study. PMID- 1626030 TI - Two compartments of slowly exchangeable sodium in bone. PMID- 1626031 TI - The Institute of Physical Sciences in Medicine 1991 Award. Founders' Prize 1991. PMID- 1626032 TI - Renal effects of head-out water immersion in humans: a 15-year update. PMID- 1626033 TI - Golgi tendon organs in mammalian skeletal muscle: functional properties and central actions. PMID- 1626034 TI - Nonsteroidal signals originating in the gonads. AB - The discovery of the various peptide factors in the gonads followed different paths. A number of factors were specifically searched for because of physiological experiments that predicted that an activity from the gonads was necessary to explain phenomena. Such was the case for gonadal steroids and for such peptide factors as inhibin, MIS, OMI, FRP, seminal plasma inhibin, relaxin, PA factor and other proteases, and ABP. In the process other factors such as activin and follistatin were serendipitously discovered. A second group of factors was discovered because in vitro experiments of various combinations of gonadal cell types failed to replicate in vivo findings, suggesting missing signals. Such substances are the panoply of growth factors aiding in differentiation and growth promotion and inhibition: LS and LI, P-Mod-S, clusterin, and various components of the ECM. Finally, and most recently, another set of peptides has been identified because immunological or molecular probes have been used to search gonadal tissue for factors originally discovered elsewhere; these include POMC, GnRH-like peptide, oxytocin, AVP, angiotensin, ANF, CRF, neural peptides, and c-mos. Our understanding of the relationship of most of these peptides to the local signals necessary for gonadal function is still very elementary. Clearly some like relaxin and inhibin function as important hormones, and ABP, for example, probably functions importantly in transporting testosterone down the tubule. Most local paracrine or autocrine peptide signals appear to act in relationship to gonadotropin levels probably in local differentiation in the process of gamete maturation, but this is only conjecture at this point. No experimental verification that any of these factors is involved in follicle selection for recruitment or for atresia is yet available. For many of the factors local receptors have not yet been identified. The richness of the variety of peptides in the gonads suggests that microanalysis of cell-cell signaling would be rewarding, but at the time of this writing such investigations are not yet possible. PMID- 1626035 TI - Selective attention in auditory processing as reflected by event-related brain potentials. AB - Measures of event-related brain potentials (ERPs) have revealed two kinds of selective-attention mechanisms that operate on attended and unattended auditory stimuli. The processing negativity of the ERP reveals a mechanism of intramodal selective attention in the auditory cortex controlled by the frontal cortex. This mechanism selects attended auditory stimuli for further processing when they differ from unattended stimuli in location or tonal frequency. Studies of intermodal selective attention have compared auditory ERPs during auditory and visual attention. At least in part different brain mechanisms may be involved in the selection of auditory stimuli among other auditory stimuli (intramodal selective attention) and in the selection of auditory stimuli among visual stimuli (intermodal selective attention). This is suggested by the results showing that the earlier component of the processing negativity, which is generated in the auditory cortex during intramodal selective attention, differs in scalp distribution from the early attention-related negativity elicited during intermodal selective attention. With respect to the unattended auditory stimuli, ERP studies of selective attention suggest that physical features of these stimuli are extensively processed. This is shown by the mismatch negativity component of the ERP, which is usually elicited by infrequent physical deviations in an auditory stimulus sequence both when this sequence is attended and when it is ignored. This would be impossible if the physical stimulus features were not extensively processed, even in the absence of attention. PMID- 1626036 TI - Cardiovascular reactivity in Type A and B males to mental arithmetic and aerobic exercise at an equivalent oxygen uptake. AB - Cardiovascular hyperreactivity (i.e., response in excess of metabolic requirements) to psychological stress has been implicated in the development of coronary heart disease. The purpose of this study was to evaluate cardiovascular hyperreactivity to psychological stress in Type A and B subjects. Fifteen Type A and 15 Type B young men performed mental arithmetic and cycle ergometry tasks. Linear regressions were calculated for each dependent variable during exercise with oxygen uptake serving as the independent variable. All cardiovascular variables were significantly correlated (p less than .0001) with oxygen uptake during exercise. The regression equations obtained during exercise were then used to predict the value of each cardiovascular variable at the oxygen uptake level obtained during mental arithmetic for each person. Repeated measures ANOVA compared responses observed during arithmetic with responses predicted from exercise at an equivalent oxygen uptake in Type A and B subjects. Heart rate, total peripheral resistance, and mean arterial pressure were significantly greater (p less than .0001) and stroke volume was significantly lower (p less than .0002) during arithmetic than during exercise, while Heather index, cardiac output, and arteriovenous oxygen difference did not differ significantly. No significant differences were found between Type A and B males. Results demonstrated that cardiovascular hyperreactivity was equally robust across Type A and B subjects. PMID- 1626037 TI - Cardiovascular responses to the combination of caffeine and mental arithmetic, cold pressor, and static exercise stressors. AB - The present study examined cardiovascular responses to the combination of caffeine (250mg) and mental arithmetic, cold pressor, and static exercise stressors in 48 healthy males. Subjects were tested in a within-subject, placebo controlled, double-blind design. Repeated measurements of heart rate, finger temperature, respiratory sinus arrhythmia, forearm blood flow, and blood pressure were obtained during a pre-drug resting baseline, a post-drug resting baseline, the three stressor tasks, and a recovery baseline. The primary analyses were 2(Drug) x 5(Period) x 6(Stress Order) MANCOVAs using pre-drug baseline values as covariates. Significant period main effects were observed for all measures. Significant drug main effects were observed for blood pressure, finger temperature, respiratory sinus arrhythmia, and forearm blood flow. The significant changes in blood pressure and finger temperature produced by caffeine combined in an additive fashion with the effects produced by the stressors. Significantly greater increases in forearm blood flow and heart rate during mental arithmetic on the caffeine day suggested a potentiation of sympathetic, beta-adrenergic activity. Questionnaires administered during baseline periods to assess psychological responses to stress and caffeine revealed a potentiation of anxiety and anger responses to stress on the caffeine day. PMID- 1626038 TI - Developmental changes in the duration of attention to unfamiliar stimuli in the rat. AB - The purpose of the present study was to examine developmental changes in the duration of attention to novel auditory stimuli in rats from infancy to adulthood. In all experiments, the cardiac component of the orienting response was used as the index of attention. In the first experiment 16-, 23-, 30-, and 75 day-old rats were exposed to a novel auditory stimulus for 60 s. Animals of all four ages exhibited a marked decrease in heart rate in response to this stimulus. Although there were no significant effects of age on the magnitude of the cardiac response, there were dramatic developmental differences in the persistence of the response. The 16-day-olds maintained a decrease in heart rate for the entire stimulus period, whereas heart rate returned to baseline in the 75-day-olds after only 40 s. The duration of the cardiac response of the 23- and 30-day-olds was between these extremes. In Experiments 2A and 2B the effect of stimulus complexity on duration of the cardiac response was examined. Increasing stimulus complexity prolonged the deceleratory response in the 30-day-olds (Experiment 2A), and decreasing stimulus complexity decreased the duration of the cardiac response in the 16-day-olds (Experiment 2B). The results of these experiments were discussed in the context of Cohen's and Porges's two-phase theories of attention. The findings demonstrate that the initial attention-getting or reactive phase of attention did not change with age, but that the duration of the attention-holding or sustained phase decreased substantially during development. PMID- 1626039 TI - Third ventricle enlargement and lower heart rate levels in a high-risk sample. AB - Heart rate activity and computed tomographic measures of structural brain abnormalities were evaluated in 32 individuals with a genetic risk for schizophrenia (offspring of schizophrenic mothers). Heart rate activity was assessed in 1962 when the subjects were a mean age of 15.1 years. Diagnostic and computed tomography assessments were conducted in 1980. Compared to individuals with normal third ventricles, individuals with enlarged third ventricles evidenced significantly lower heart rate levels overall and significantly lower heart rate during rest and during the periods preceding conditioning and test for conditioning stimulus trials. These effects were independent of age, psychiatric diagnosis, and abnormalities in other brain regions. Difficulties in interpretation posed by the index of brain abnormality employed and by the 18 year time interval between the heart rate and computed tomography assessments are discussed. Together with prior evidence of a relationship between third ventricle enlargement and reduced electrodermal responsiveness in the same subjects, these findings provide a preliminary indication that enlargement of the third ventricle may involve damage to diencephalic structures involved in autonomic nervous system activity. PMID- 1626040 TI - Increased salivary cortisol in severe dental anxiety. AB - The aim of the present study was to investigate the feasibility of saliva collection from highly anxious dental patients and to evaluate whether salivary cortisol concentrations could discriminate between 13 highly anxious dental patients and 13 non-anxious subjects. Whole mixed saliva was sampled by suction after stimulation with citric acid crystals. Salivary free cortisol levels were measured in duplicate by radioimmunoassay. Collection of saliva took 2-5 min and was not experienced as unpleasant. Salivary free cortisol concentrations were significantly elevated if the patients manifested anxiety according to the scores on the Dental Anxiety Scale. The measurement of salivary cortisol may be a convenient method for the assessment of dental anxiety. PMID- 1626041 TI - The effect of common versus distinctive stimulus features on electrodermal orientation to significant stimuli. AB - The relationship between electrodermal responsivity and stimulus similarity was previously demonstrated in a series of studies. These studies were guided by a feature-matching model according to which similarity is an additive function of the common and distinctive features of the stimuli. In these experiments common and distinctive features were simultaneously manipulated, thus confounding the effects of the two sets of features. In the present experiment, we examined the separate effects of these two sets of features by an independent manipulation of common and distinctive components of the stimuli. A modified version of the guilty knowledge technique was employed, with compound pictorial and verbal stimuli (schematic faces and verbal descriptions of people) as the relevant items memorized by the subjects. Skin conductance responses were measured during the subsequent presentation of a stimulus sequence comprised of a test stimulus, which shared some common components with the relevant stimulus, and several neutral control stimuli. As hypothesized, a larger number of distinctive components resulted in decreased responsivity. Yet, contrary to our expectation, the number of common components of the relevant and test stimuli had no effect on responsivity. Several hypotheses are suggested to account for this unexpected result. PMID- 1626042 TI - Scopolamine effects on visual information processing, attention, and event related potential map latencies. AB - We measured performance and event-related brain potential (ERP) map latencies in 12 subjects during four visual discrimination tasks to compare the timing of scopolamine effects on information processing and attention. "Topographic component recognition" found ERP map latencies at times of best fit with a component model map. This "common topography" criterion minimized topographic differences among conditions to facilitate latency interpretations. Scopolamine slowed N1 latency in all tasks, and P3 and reaction time in some tasks. The drug delayed responses to easy targets more than to hard targets. It also induced a disproportionate N1 delay for unilateral high spatial frequency gratings. Both effects reflect a scopolamine-induced impairment when processing targets that usually capture attention. Scopolamine also impaired accuracy for unilateral high spatial frequency gratings, and for gratings presented at probable locations, confirming and extending previous findings. Scopolamine-induced P1 and N1 delays showed that visual processing was affected. Several results were inconsistent with a serial stage model. We suggest that scopolamine both delays selected processes and impairs a processing mode based on automatic capture of attention, inducing more serial processing. PMID- 1626043 TI - Can echoic memory store two traces simultaneously? A study of event-related brain potentials. AB - The mismatch negativity, a component of the event-related brain potential elicited by infrequent deviants in sequences of auditory stimuli, is presumably generated by an automatic mismatch process in a mechanism that compares the current stimulus to the trace of the previous one. The present study addressed the possible simultaneous existence of two such traces. Two equiprobable (45% each) frequent stimuli ("standards"), one of 600 Hz and the other of 700 Hz, were presented together with an infrequent (10%), "deviant" stimulus which was of different frequency in different blocks. These deviants elicited a mismatch negativity, though a smaller one than that obtained in corresponding blocks with only one standard stimulus. Two aspects of the present results from the blocks with two standard stimuli implicate two parallel stimulus traces in these blocks: 1) deviants elicited a mismatch negativity (MMN) of approximately the same amplitude when preceded by sequences of four identical standards as when preceded by sequences of four stimuli containing both standards; 2) in contrast to the one standard condition, the magnitude of stimulus deviance did not affect the MMN component elicited by the different deviants. PMID- 1626044 TI - Digital filtering: background and tutorial for psychophysiologists. AB - Digital filtering offers more to psychophysiologists than is commonly appreciated. An introduction is offered here to foster the explicit design and use of digital filters. Because of considerable confusion in the literature about terminology important to both analog and digital filtering, basic concepts are reviewed and clarified. Because some time series concepts are fundamental to digital filtering, these are also presented. Examples of filters commonly used in psychophysiology are given, and procedures are presented for the design and use of one type of digital filter. Properties of some types of digital filters are described, and the relative advantages of simple analog and digital filters are discussed. PMID- 1626045 TI - Local distribution and dosimetry of 226Ra in the trabecular skeleton of the beagle. AB - Young adult beagle dogs received a single injection of 38.1 kBq/kg body wt 226Ra and were serially sacrificed at 4 to 2955 days postinjection. Samples of sites of trabecular bone in the lumbar vertebral body, proximal ulna, and distal femoral metaphysis and epiphysis were analyzed autoradiographically. The time-dependent changes in the average 226Ra concentrations in the four regions were analyzed in terms of a compartmental model. The clearance rate from the lumbar vertebral body was about four times more rapid than for the proximal ulna and distal femoral epiphysis. Ratios of hotspot to diffuse label concentrations varied from about 10 to 23. The dose rate to the endosteum ranged between 8.7 and 39.5 mGy/day initially and 4 and 10.5 mGy/day toward the end of the observation period. Mean marrow dose rates were lower by a factor of 3 to 9.5. During their residence time the nuclei of bone lining cells receive a maximum dose of 8 Gy in the proximal ulna (2955 days after injection) and a minimum dose of 0.63 Gy in the lumbar vertebra (2955 days after injection). This corresponds on the average to 17 and 1.4 alpha-particle hits to the cell nuclei, respectively. PMID- 1626046 TI - Early changes in mouse urinary bladder function following fractionated X irradiation. AB - Functional changes in the mouse urinary bladder following single-dose or fractionated irradiation were assessed by cystometry, i.e., by measuring the intravesical volume-pressure relationship during transurethral filling. The early response presented as a dose-dependent and transitory decrease in the reservoir function of the organ as defined by the intravesical volume at a filling pressure of 10 or 20 mm Hg, V10 or V20. The quantal dose response used in the present study was a reduction in the individual bladder volume (V10 and V20) by at least 50%. After single doses greater than or equal to 10 Gy, the reaction occurred between Days 7 and 25 with maximum prevalence between Days 7 and 14. The individual duration of the response was 3-9 days. Treatment with single doses and 2, 3, 5, and 10 fractions demonstrated a significant sparing effect with ED50 values of 18.3, 24.9, 26.8, 29.8, and 38.0 Gy, respectively. The linear-quadratic model fitted the data reasonably well when tested according to Tucker (Int. J. Radiat. Oncol. Biol. Phys. 10, 1933-1939, 1984). The alpha/beta ratios estimated with different two-step techniques ranged from 11.1 to 12.4 Gy. Analysis of the data as proposed by Thames et al. (Int. J. Radiat. Biol. 49, 999-1009, 1986) yielded an alpha/beta value of 13.9 Gy (95% confidence limits 8.4 and 24.6 Gy), illustrating a fractionation effect typical for acutely responding tissues, although no clear cell depletion occurred in the urothelium. PMID- 1626047 TI - Effect of prostaglandins, inositol 1,4,5-trisphosphate, and phorbol esters on radiation-induced decreases in calcium influx in rat brain synaptosomes. AB - Gamma irradiation (60Co) reduced KCl-stimulated voltage-dependent uptake of 45Ca2+ in rat whole-brain synaptosomes. Prostaglandins, inositol 1,4,5 trisphosphate, and phorbol esters were tested for their ability to inhibit radiation-induced decreases in calcium influx. None of the compounds tested alone completely prevented radiation-induced decreases in calcium uptake, but some drug combinations did inhibit decreases. Results suggest that radiation-induced decreases in calcium uptake are due to impairment of protein kinase C activity and mobilization of calcium by these drugs. PMID- 1626048 TI - Effect of fluoride on inhibition of plasma membrane functions in Chinese hamster ovary cells photosensitized by aluminum phthalocyanine. AB - Fluoride inhibits photohemolysis induced by chloroaluminum phthalocyanine tetrasulfonate (AlPcS4) when it is added to dye-loaded human erythrocytes prior to light exposure (E. Ben-Hur, A. Freud, A. Canfi, and A. Livne, Int. J. Radiat. Biol. 59, 797-806, 1991). This is due to formation of a complex of F- with Al3+, leading to selective release and/or modified dye binding with some proteins so that the effective photochemical reaction is prevented. In this work we used F- as a probe to evaluate the involvement of the plasma membrane functions of Chinese hamster ovary cells in photocytotoxicity induced by chloroaluminum phthalocyanine (AlPc). Fluoride was found to protect against killing of cells photosensitized by AlPc but not AlPcS4. Plasma membrane damage induced by AlPc photosensitization was manifested by K+ leakage, membrane depolarization, inhibition of glucose and amino acid uptake, and Na+/K(+)-ATPase inactivation. The latter enzyme system was found to be the one most sensitive to inhibition by the combination of AlPc and PDT among the membrane functions studied, and was completely protected by F- in the dose range at which up to 95% of the cells are killed. Of the other membrane functions only glucose transport was slightly protected by F-. It is concluded that damage to the plasma membrane is involved in cell killing induced by AlPc photosensitization and that the plasma membrane enzyme Na+/K(+)-ATPase is a probable candidate as a critical target. PMID- 1626049 TI - Evidence that DNA double-strand breaks initiate the phenotype of delayed reproductive death in Chinese hamster ovary cells. AB - A persistently reduced cloning efficiency occurs in many of the cloned progeny of Chinese hamster ovary (CHO) cells surviving X irradiation, a stable phenotype we have previously termed delayed reproductive death (Int. J. Radiat. Biol. 60, 483 496, 1991). We now report that this phenotype is also induced by the alkylating agent ethyl methanesulfonate (EMS), but not by irradiation with ultraviolet light. The restriction endonuclease HinfI, which binds at G [symbol: see text] ANTC DNA sequences and generates cohesive-end double-strand breaks, was also efficient in inducing delayed reproductive death. On the other hand, an X-ray sensitive CHO mutant, xrs-5, which is defective in the repair of DNA double strand breaks, did not show this phenotype following X irradiation. These results suggest that DNA double-strand breaks, as well as the endogenous repair processes for these breaks, are associated with the induction of the delayed reproductive death phenotype in CHO cells. The possible mechanism for the induction of delayed reproductive death by EMS is discussed. PMID- 1626050 TI - Transformation of C3H 10T1/2 cells with 4.3 MeV alpha particles at low doses: effects of single and fractionated doses. AB - Oncogenic transformation of C3H 10T1/2 cells was determined after exposure to graded doses of 4.3-MeV alpha particles LET = 101 keV/microns. The source of alpha particles was 244Cm and the irradiation was done in an irradiation chamber built for the purpose. Graded doses in the range of 0.2 to 300 cGy were studied with special emphasis on the low-dose region, with as many as seven points in the interval up to 10 cGy. The dose-effect relationship was a complex function. Transformation frequency increased with dose up to 2 cGy; it seemed to flatten at doses between 2 and 20 cGy but increased again at higher doses. A total of 21 cGy was delivered in a single dose or in 3 or 10 equal fractions at an interval of 1.5 h. An inverse dose-protraction effect of 1.4 was found with both fractionation schemes. Measurements of the mitotic index of the population immediately before the various fractions revealed a strong effect on the rate of cell division even after very low doses of radiation. Mitotic yield decreased markedly with the total dose delivered, and it was as low as 50% of the control value after 4.2 cGy and 20% after 14 cGy with both fractionation schemes. PMID- 1626051 TI - Inactivation action spectra of Bacillus subtilis spores with monochromatic soft X rays (0.1-0.6 nm) of synchrotron radiation. AB - Five types of Bacillus subtilis spores differing in DNA repair and recombinational capacities were exposed in vacuum to monochromatic soft X rays from synchrotron radiation. The inactivation rate constants were obtained from exposure-survival curves upon irradiations at 12 wavelengths in the range of 0.1000 nm (12.40 keV) to 0.6000 nm (2.066 keV). Spores of two repair-deficient strains, UVS (uvrA ssp) and UVP (uvrA ssp polA), exhibited almost equal sensitivities to those of wild-type UVR+, while those of two recombination deficient strains, RCE (recE) and RCF (recF), exhibited higher sensitivities in the whole wavelength range. This suggested that the repair of DNA damage produced by soft X rays was dependent on the recombinational capabilities. Inactivation action spectra based on photon fluence showed that the effectiveness of the radiation increased as the wavelengths became longer. Abrupt changes in the effectiveness occurred around the wavelengths corresponding to the absorption edges of K-shell electrons of phosphorus and calcium. In both cases, the sensitivity was the highest at the wavelengths of the resonance absorption peak, the next highest at those of the higher energy, and the lowest at the lower energy. Mass energy absorption coefficients of spores were obtained from the transmission of a flake made of spores. They were used to derive inactivation action spectra based on absorbed doses. In these spectra, basal levels of the sensitivity seemed constant, and enhancements of the sensitivity were observed consistent with the absorption by calcium and phosphorus. Thus calcium and phosphorus atoms were the predominant targets for the absorption events leading to the inactivation of spores in the wavelength range examined. PMID- 1626052 TI - Linear-quadratic analysis of radiosensitization by halogenated pyrimidines. I. Radiosensitization of human colon cancer cells by iododeoxyuridine. AB - Radiosensitization by iododeoxyuridine (IdU) is a method of enhancing cell killing in the radiotherapy of human cancers, especially for tumors that proliferate faster than the surrounding normal tissues, such as might appear in brain or liver. We have investigated in vitro the relationship between the amount of thymidine replacement by IdU and the resulting radiosensitization in two human colon cancer cell lines, HCT 116 and HT 29, with differing inherent sensitivities to X rays. The results show that an increase in the initial slope of the cell survival curve was the predominant mode of radiosensitization. In this situation, the emphasis on changes in the initial slope suggest the use of a survival curve model that contains the initial slope as a defined variable, which the traditional single-hit, multitarget model does not. We present our analyses mainly in terms of alpha (initial slope) and changes in surviving fraction at 2 Gy and also as a modified form of sensitizer enhancement ratio that describes the dose-modifying factor of IdU at a single radiation dose of 2 Gy (SER 2 Gy). Iododeoxyuridine is an effective radiosensitizer in both cell lines, but IdU appears especially effective in increasing the initial slope of the more radioresistant line, the HT 29 cells. PMID- 1626053 TI - Linear-quadratic analysis of radiosensitization by halogenated pyrimidines. II. Radiosensitization of human colon cancer cells by bromodeoxyuridine. AB - As a continuation of the studies in Part I (Miller, Fowler, and Kinsella, Radiat. Res. 131, 000-000, 1992), which examined the radiosensitizing effects of iododeoxyuridine (IdU), similar experiments with bromodeoxyuridine (BrdU) were conducted concurrently to characterize its effects on the shape of the radiation survival curves of cells of two human colon cancer cell lines, HT 29 and HCT 116. The efficiency of radiosensitization by BrdU, expressed as a function of percentage thymidine replacement, was lower when compared to IdU in both cell lines. However, the major radiosensitizing effect of BrdU was manifest as an increase in the initial slope (alpha), just as observed for IdU. However, with BrdU, in contrast to IdU, an increase in curvature (repairable damage) was also evident. Cells of the more radiosensitive line, HCT 116, showed less sensitization by either BrdU or IdU than cells of the more radioresistant line, HT 29. These results were consistent with the proposed mechanism of radiosensitization being an increase in the single-hit character of low-LET radiation. It follows that the radiosensitizing effects of both analogs were largest in the low-dose region of the survival curve. PMID- 1626054 TI - Nurse denied pay differential for unscheduled work. PMID- 1626055 TI - Are nurses held to same standards of care as physicians? Case in point: Alef v. Alta Bates Hospital (6 Cal Rptr. 2d 900-CA [1992]). PMID- 1626056 TI - A new method for monitoring the cerebrovascular response to acetazolamide using 99mTc-DTPA-HSA. AB - We developed a new method for monitoring the cerebrovascular response to acetazolamide using technetium-99m diethylenetriaminepentaacetic acid human serum albumin (99mTc-DTPA-HSA). We infused 740 M Bq (20 mCi) of 99mTc-DTPA-HSA intravenously and carried out dynamic scanning of the anterior view of the head for 50 minutes. Ten minutes after the start of scanning, 1,000 mg of acetazolamide was injected intravenously. In three normal volunteers, the radioactivity in brain increased for an average of 8 minutes after the injection of acetazolamide and then remained relatively stable. The average of dilatation index [(peak count/the count just before acetazolamide injection-1)x 100] was 16.1. Our method enabled us to observe vasodilation caused by acetazolamide straight, and may be of value in assessing cerebral perfusion reserve easily and quantitatively. PMID- 1626057 TI - Pancreatic angiography using balloon catheter occlusion and a vasoconstrictor. AB - When a vasoconstrictor (noradrenaline) was injected during occlusion of the common hepatic artery with a balloon catheter, the vasoconstrictor flowed only into the proper hepatic artery and constricted it. The balloon was immediately deflated and contrast medium injected into the common hepatic artery. The flow of the contrast medium into the gastroduodenal artery was then increased, clearly visualizing the entire pancreatic-duodenal arcade. PMID- 1626058 TI - Clinical evaluation of assistant diagnostic system for mammograms using the auto analyzing method. AB - Clinical usefulness of a newly developed auto-analyzing system of mammograms to search the abnormal dense areas such as cancer lesions was studied. 345 breasts including 86 cancers, 52 mastopathies, 18 fibroadenomas, 13 cysts, 4 lipomas and 172 normals were analyzed and compared with final diagnosis. 84 of 86 cancer lesions were correctly pointed out (sensitivity: 97.9%). Based on the gradient of the density, the ranking of the cancer or calcified lesions among suspected regions in a mammogram was decided. 55 lesions of them (64.0%) were ordered at the first rank and 83 (96.5%) were in the upper three ranks. 68 of 74 breasts with calcifications were correctly diagnosed and 48 of them were ranked in the upper three ranks. Although further improvement of the system is needed, this system will be a useful assistance for screening the breast cancer in the analyses of mammograms. PMID- 1626059 TI - A case of abdominal cystic lymphangioma: cobweb appearance on ultrasonography. AB - A case of abdominal cystic lymphangioma is described. Our sonographic examination showed a large multilocular cyst with a cluster of honeycomb cysts revealing a cobweb appearance, which correlated with the pathologic specimen, and revealed characteristics of the disease. Sonographic appearance may be helpful in differentiating abdominal cystic lymphangioma from other multilocular cystic tumors. PMID- 1626060 TI - Case report of malignant splenic tumor. AB - Primary angiosarcoma and malignant lymphoma of the spleen are uncommon. We report such tumors in a 44-year-old-woman and a 51-year-old-man. The value of diagnostic imaging by US and CT is emphasized. These techniques can establish the solid nature of the mass and may be the first methods to suggest malignancy. PMID- 1626061 TI - Extrahepatic portal obstruction with intestinal malrotation: a case report. AB - We report the case of a 20-year-old woman with extrahepatic portal obstruction, anomalous branching of the celiac artery, and intestinal malrotation with duodenal dysgenesis. The patient had no history of neonatal event and had normal liver function. The combination of these abnormalities, rarely reported in the literature, suggests that the extrahepatic portal obstruction in this case might be congenital in origin. PMID- 1626062 TI - CT and MR findings in diastematomyelia, with embryogenetic consideration. AB - Diastemstomyelia is an extremely rare disorder that is seldom found among the Japanese. This paper presents two Japanese patients, a newborn male and a newborn female, with diastematomyelia. CT demonstrated bony spurs more clearly than plain film, and magnetic resonance images indicated split cords and associated anomalies. Although the embryogenesis of diastematomyelia has not been clearly elucidated, the coincidence of levels of associated anomalies and diastematomyelia in our cases and in the literature supports Bremer's embryogenetic explanation of persistent accessory neurenteric canal. PMID- 1626063 TI - Assessing the health risks of priority substances under the Canadian environmental protection act. AB - The Canadian Environmental Protection Act (CEPA) came into force in June 1988. This legislation provides the federal government with broad powers to deal with health and environmental problems posed by chemicals and the products of biotechnology throughout their life cycle. Responsibility for administering CEPA is shared between the Department of the Environment and the Department of National Health and Welfare. Part II of the Act, the "toxic substances" provisions, enables the federal government to impose controls on substances new to Canadian commerce and to address the health and environmental risks posed by existing substances. Part II of CEPA also delineates the manner in which existing substances are to be selected for assessment (priority substances) and controlled. The first Priority Substances List was published in February 1989. The 44 entries on this list include discrete chemicals, classes of chemicals, and complex mixtures of chemicals; the Department of the Environment and the Department of National Health and Welfare must ascertain whether these substances pose a risk (are "toxic" as defined in CEPA) to the environment or to human health by February 1994. This paper outlines the administrative arrangements for conducting risk assessments and the requirements for ascertaining whether a substance is "toxic" with respect to human health under CEPA. The rationale for deeming dioxins and furans, the first two priority substances to be assessed, as "toxic" with respect to human health is also described. PMID- 1626064 TI - An analysis of exposure rate effects for benzene using a physiologically based pharmacokinetic model. AB - A new physiological pharmacokinetic model was used to explore the effect of exposure rate on the rate of formation of several crucial metabolites of benzene. Metabolite formation was compared following exposure to benzene over the course of an 8-hr workday and following a single exposure for 15 min. These exposures were based on the permissible exposure limit and short-term exposure limit of the benzene standard set by the Occupational Safety and Health Administration. The model was parametrized using in vitro and in vivo experimental data on benzene toxicokinetics and metabolism. Ranges, rather than fixed values, were assigned to the parameters. Model predictions show that the amounts of hydroquinone, catechol, and muconaldehyde formed in the body following a peak exposure to 32 ppm of benzene over 15 min are on average 20% higher than those formed following an equivalent dose of 1 ppm over an 8-hr period. The health consequences of these findings and the implications for policy concerning short-term exposure limits are discussed. PMID- 1626065 TI - Pesticide tolerances and their relevance as safety standards. AB - Following an investigation of the relationship between pesticide tolerances and safety, it is concluded that pesticide tolerances are not relevant as safety standards. This conclusion is based upon the findings that theoretical exposures to legal levels of pesticides in the diet may pose greater than negligible risks, while exposures to most illegal residues are of no apparent toxicological significance. Thus, the common and logical views that "legal" residues are "safe" while "illegal" residues are "unsafe" are not supported by scientific evidence. Pesticide tolerances do serve important roles as enforcement tools, and tolerance enforcement programs are useful in the regulation of international trade and provide economic disincentives that may discourage pesticide misuse and emphasize compliance with regulations. Since tolerances are not appropriate as safety standards, however, legislative food safety proposals focusing upon revocation or reduction of tolerances and upon increasing enforcement capabilities may result in little benefit to public health. PMID- 1626066 TI - Incidence of developmental defects at the no observed adverse effect level (NOAEL). AB - Bioassay data from Teratology, Vol. 1 (1968) through Vol. 40 (1990), were utilized which were sufficient to establish no observed adverse effect levels (NOAEL's) for 120 experiments on 93 developmental toxicants in animals. The observed incidence (risk) at the NOAEL was calculated as the proportion of affected fetuses minus the proportion affected in the control animals. This calculation did not require any dose-response modeling. Data were primarily from experiments on rats and mice with a few studies on rabbits and hamsters. There did not appear to be differences in risks at the NOAEL among these four species. For each experiment, the risk at the NOAEL was tabulated for all of the adverse effects which shared the same NOAEL. Since the observed risk at the NOAEL for either dead/resorbed or abnormal fetuses exceeded 1% in about one-fourth of the cases, this suggests that a benchmark dose with a risk on this order would eliminate the higher risks and serve as a basis for establishing reference doses. If the lower confidence limit on a benchmark dose is used in place of the NOAEL, better experimental designs with more animals would result in tighter confidence limits, giving larger (less stringent) reference doses than poorer experiments. PMID- 1626067 TI - Statistical properties of the NOAEL. AB - The use of the no observed adverse effect level (NOAEL) in setting allowable exposure levels for noncancer endpoints is a source of controversy. Based on computer simulations and empirical studies, several authors have criticized the use of the NOAEL in terms of its sensitivity to sample size and its high sampling variability from experiment to experiment. The purpose of this paper is to derive the statistical distribution of the NOAEL. Using Weibull models, we investigate the impact of the shape of the underlying dose-response curve on the distribution of the NOAEL. The results confirm previous criticisms of the NOAEL and show that average risk levels associated with the NOAEL may be substantial. These results provide additional motivation for developing alternative approaches to risk assessment. PMID- 1626068 TI - Does the animal-to-human uncertainty factor incorporate interspecies differences in surface area? AB - Risk assessment practices for noncarcinogens typically employ an uncertainty factor (UF) for animal-to-human extrapolation when defining acceptable levels for humans based on animal studies. EPA has interpreted the use of this factor as addressing interspecies differences due to dose normalization via surface area (exposure-dose relationships) and to innate differences in species susceptibility (dose-response relationships). Thus EPA has concluded that dose normalization via surface area is not necessary when using animal studies to define acceptable levels for noncarcinogens for humans. In this report we challenge this position on both theoretical and practical grounds. It is recommended that the UF for animal-to-human extrapolation for noncarcinogens in the risk assessment process and the technique for dose normalization be considered distinctly. PMID- 1626069 TI - Use of human data in quantitative risk assessment of carcinogens: impact on epidemiologic practice and the regulatory process. AB - Epidemiologic data are increasingly being used to assess cancer risk from chemicals as their value is recognized and as more and better studies become available. Weight-of-evidence approaches are now available for classifying the experimental and epidemiological evidence regarding human carcinogenicity. When the human data are extensive and of good quality, they should be given substantial weight in assessing risk. Both the positive and the negative epidemiologic data should be used in a quantitative risk assessment (QRA), because only then can an unbiased risk assessment be derived. Good-quality epidemiological studies are those with sound methodology, lack of bias, long enough follow-up times to observe a carcinogenic response, adequate exposure information, and dose-response information. Before a lack of carcinogenicity can be inferred, it is essential that the exposures be of substantial duration and intensity, and that the number of exposed persons be reasonably large. Epidemiologists need to give more attention to exposure assessment, because lack of quantitative exposure information is often the limiting factor that prevents the use of epidemiologic data in QRA. Development of methods to estimate historical workplace exposure intensities from surrogate industrial hygiene variables should receive high research priority, since they have the potential to increase the usefulness in QRA of many epidemiologic studies that have limited exposure information. Several frequently used surrogates for exposure measurements have limitations or pitfalls in their use. In particular, the use of "ever/never" exposed has a large potential to produce falsely negative results by means of a "dilution" effect, especially in the common case where the exposure distribution is skewed. Duration of exposure (rather than duration x intensity) may also give misleading results. There is little information to suggest that synergistic exposures to multiple toxicants in an industrial environment are likely to invalidate QRAs, probably because few studies have identified a group of workers with major workplace exposures to multiple carcinogens that cause the same type of cancer. Most of the interactive effects which have been identified to date are between smoking and some occupational carcinogen, so this possibility needs careful evaluation for smoking-related diseases. It is important to evaluate dose-response gradients in a QRA to obtain maximum precision and accuracy in the resulting risk coefficient. The analysis should take into account an appropriate cancer induction period. Various methods to account for cancer induction times are compared; those that incorporate a lag period or model the induction-time distribution are superior to other methods.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1626071 TI - Antinuclear antibodies. PMID- 1626070 TI - Molecular biology of nuclear autoantigens. AB - This article provides a historical overview of the application of molecular and immunologic techniques to the analysis of autoantigenic structure and function, as well as to autoantibody recognition of protein and nucleic acid autoantigens. Examples presented here illustrate the role of autoantibodies as tools in the elucidation of the autoimmune components of cellular ribonucleoproteins. In turn, the subsequent molecular dissection of autoantigenic ribonucleoproteins has advanced understanding of autoantibody specificities. The nature of autoantibodies reactive with various proteins and nucleic acids will be the subject of the following articles in this issue. Taken together, these studies of antibody-antigen interactions that arise during the autoimmune response have revealed novel mechanisms of molecular recognition within the RNP autoantigens. These findings are of general importance for understanding basic cellular processes and have contributed to our knowledge of the underlying mechanisms of immunoregulatory abnormalities that arise in autoimmune diseases. PMID- 1626072 TI - Antibodies to snRNPs in systemic lupus erythematosus. AB - Antibodies to the Sm and RNP antigens are diagnostic hallmarks in patients with systemic lupus erythematosus. Both antigens are located on the U1 snRNP (small nuclear ribonucleoprotein particle), a complex of a small RNA and associated proteins that carry the antigenic determinants. This particle also plays an essential role in messenger RNA processing within the cell nucleus. Newer diagnostic techniques are available for detection of anti-Sm and antiRNP antibodies (the latter are now more appropriately called anti-U1 RNP antibodies) and a great deal of information on the molecular biology of snRNPs is currently available. PMID- 1626073 TI - Anti-Ro in Sjogren's syndrome and systemic lupus erythematosus. AB - Anti-Ro autoantibodies are frequently found in the sera of patients with Sjogren's syndrome, systemic lupus erythematosus, and subacute cutaneous lupus erythematosus as well as in the sera of mothers of infants with the neonatal lupus syndrome. Close associations have been found between anti-Ro and a number of clinical manifestations, particularly including hematologic cytopenias, heart block, and photosensitive skin rashes. Serologic and genetic associations have been found between anti-Ro and anti-La, rheumatoid factor, hypergammaglobulinemia, the histocompatibility alleles DQ1 and DQ2, and alleles of the T-cell receptor beta chain gene. The origin of anti-Ro and other autoantigens is thought to relate to the etiology of Sjogren's syndrome and systemic lupus erythematosus and remains the most fundamental unanswered question preventing a comprehensive understanding of these diseases. PMID- 1626074 TI - Anti-La antibodies. AB - Anti-La antibodies usually occur in sera with anti-Ro antibodies and represent important serologic markers of Sjogren's syndrome and neonatal lupus erythematosus. In addition to their diagnostic and prognostic significance, anti La antibodies have proved valuable reagents for molecularly characterizing its antigenic target, which is a 47 kD ribonucleoprotein located in the nucleus and cytoplasm of mammalian cells. The isotype distribution and fine specificity of the anti-La response as well as its associations with HLA-DR and DQ loci suggest that these autoantibodies arise by a T cell-dependent, antigen-driven mechanism. Further insights into the mechanisms of anti-La production in humans may be gained by studying experimental animal models that develop these antibodies spontaneously or through induction by various immunization protocols. PMID- 1626075 TI - Antibodies to the p70/p80 (Ku) antigens in systemic lupus erythematosus. AB - The Ku (p70/p80) autoantigen, a heterodimer consisting of 70 kDa (p70) and 80 kDa (p80) protein subunits, is one of a group of DNA-associated autoantigens identified as targets of autoantibodies produced by patients with SLE and related disorders. Many of these DNA-protein antigens are involved in organizing the genome into transcriptionally active (euchromatin) and inactive (heterochromatin) domains. The bulk of available evidence indicates that the Ku antigen is also involved in organizing the genome, although its precise role remains unclear. Molecular cloning of the protein subunits of Ku has revealed that the structure of p70 resembles that of certain transcriptional activator proteins, and there is some evidence in vitro that Ku may increase transcriptional activity from at least two promoters. Moreover, examination of the distribution of Ku in the polytene chromosomes of insects suggests an association with transcriptionally active chromatin. The DNA-binding domain of Ku has been localized to the C terminus of p70, whereas p80 does not appear to bind DNA, and may be involved in interactions with other proteins. Epitope mapping and mutagenesis experiments have shown that the immunodominant epitope of p70 lies within the DNA-binding domain. Surprisingly, this autoepitope is not conserved between humans and mice, raising the possibility that the interaction of Ku with DNA might exhibit species specific functional differences. At least seven additional autoepitopes have been identified on the Ku particle, located on p70, p80, or both subunits. Autoantibodies to p70, p80, and DNA are produced tandemly by patients with SLE, providing evidence for an antigen-driven immune response targeting the entire Ku particle. The multiple specificities of anti-Ku autoantibodies and the tandem production of antibodies to the various constituents of the Ku particle are consistent with a role of either "molecular mimicry" or "intermolecular help" in the generation of autoimmunity to this antigen. PMID- 1626076 TI - Antibodies to histones in systemic lupus erythematosus and drug-induced lupus syndromes. AB - Antihistone antibodies are some of the most frequent autoantibodies in rheumatic diseases and can represent useful diagnostic markers in some autoimmune syndromes. Histone epitopes are often located in accessible regions of chromatin or are conformational determinants resulting from the association of several components. These observations and studies with murine models of lupus strongly support the view that histones play a direct stimulatory role in triggering autoantibody production. PMID- 1626077 TI - Anti-DNA antibodies in systemic lupus erythematosus. AB - Anti-DNA antibodies are the serologic hallmark of systemic lupus erythematosus and important markers for diagnosis and prognosis. Although a number of mechanisms for anti-DNA production have been proposed, recent evidence from human as well as murine lupus indicate a prominent role of DNA antigen drive. To identify further the basis of this response, current research is focusing on the structural features of DNA associated with immunogenicity in both the normal and autoimmune settings. Elucidating these mechanisms should thus provide insights into the pathogenesis of systemic lupus erythematosus as well as the immunologic activity of nucleic acids. PMID- 1626078 TI - Autoantibodies in scleroderma. AB - The antinuclear and antinucleolar antibodies found in patients with scleroderma are discussed. Many of the autoantigens have been characterized, the cDNA cloned and the epitopes defined. Many of the more common autoantigens are DNA-binding proteins, which are very important in transcription and in cell division. The clinical significance of the autoantibodies is discussed: their prevalence and their relation to disease manifestations and prognosis is examined. The unique exclusiveness of the major autoantibodies is discussed. The data on the immunoglobulin and IgG subclass is reviewed in relation to the overall concept that most autoantibodies in scleroderma patients represent the result of an antigen-driven response. PMID- 1626079 TI - Acquisition, generalization, and spontaneous use of color adjectives: a comparison of incidental teaching and traditional discrete-trial procedures for children with autism. AB - Incidental teaching and traditional discrete-trial procedures were used to teach two children with autism the expressive use of two color adjectives to describe preferred toys and food items. The two teaching procedures were performed in a classroom setting, and generalization and spontaneous usage were assessed at home with parents. The results demonstrated that traditional discrete-trial teaching was more efficient and produced faster acquisition and, initially, greater generalization. However, by follow-up, the incidental teaching methods resulted in equal retention, greater generalization, and equal or greater spontaneous usage. The findings indicate that although it takes a longer time for children with autism to learn with incidental teaching procedures, once they have acquired an ability, it may be more permanent. It is recommended that incidental teaching procedures be included in future language development programs for children with autism. PMID- 1626080 TI - The use of self-management procedures by people with developmental disabilities: a brief review. AB - Self-management procedures, such as self-monitoring, self-administering consequences, and self-instructing, are frequently taught to people with developmental disabilities. In this paper, research examining the use of self management procedures is reviewed and critiqued. Areas for future investigation are discussed. PMID- 1626081 TI - Treatment acceptability ratings for sexual offenders: effect of diagnosis and offense. AB - Case description methodology was used to obtain treatment acceptability ratings for mentally retarded and nondisabled (normal) sex offenders across three different offenses (masturbation, rape, and child fondling) and eight interventions. For both diagnostic groups, social-sexual skills training (SST) was the most acceptable treatment except in cases of rape, fondling of a minor, and public masturbation. For these offenses, SST was as acceptable as aversive treatments and incarceration. The addition of a positive treatment component to a preexisting aversive intervention did not result in significantly different acceptability ratings relative to ratings of aversive interventions alone. Respondent's history as a victim of sexual abuse did not affect treatment acceptability ratings for prison, medication, or use of noxious odors. PMID- 1626083 TI - Effects of picture referencing on PVC chair, love seat, and settee assemblies by students with mental retardation. AB - This study examined the effects of two indirect corrective feedback procedures on the assembly skills of five secondary students with moderate mental retardation. Picture and video referencing conditions, during which the experimenters pointed to a picture or video screen following a performance error and requested the student do the step again, were more effective than assembly photographs, sequenced pictures, sequenced pictures and modeling, and video modeling conditions. Picture referencing enabled each participant to independently assemble a 13-step, 31-piece chair that required assembly of 45 loose, assembled, or loose and assembled parts. Following the introduction of picture referencing across two more complex tasks, four students independently completed more complex love seat and settee assemblies in fewer trials than required during their initial chair assembly. This article discusses the self-correction and self management implications. PMID- 1626082 TI - Constant time delay with discrete responses: a review of effectiveness and demographic, procedural, and methodological parameters. AB - Constant time delay, a variation of progressive time delay, is a response prompting strategy designed to provide and remove prompts in a systematic manner on a time dimension. Constant time delay has two defining characteristics: (a) initial trials involve presentation of the target stimulus followed immediately by delivery of a controlling prompt; and (b) on all subsequent trials, the target stimulus is presented, a response interval of a fixed duration is delivered, the controlling prompt is provided, and a second response interval is delivered as needed. Reports of 36 studies using the constant time delay procedure with discrete behaviors were identified and analyzed. The results are described in terms of demographic variables (i.e., the types of subjects, settings, behaviors, instructors, and instructional arrangements), and the procedural parameters of the strategy. The effectiveness of the strategy and the outcome measures are summarized. Finally, the methodological adequacy of the constant time delay research is examined. Implications for practice and for further research are presented. PMID- 1626084 TI - Reduction of multiple aberrant behaviors and concurrent development of self-care skills with differential reinforcement. AB - A modified functional analysis was used to assess the behavioral function of a profoundly retarded man's self-injurious behavior (SIB). Results of that analysis showed that the behavior was most likely to occur in a demand context (self-care instructions) but was maintained by positive reinforcement in the form of attention and physical contact. The results of the functional analysis also prescribed a treatment involving differential reinforcement of alternative behavior (DRA). Further investigation showed that other aberrant behaviors, such as aggression and disruption, were members of the same functional response class as SIB. The differential reinforcement of alternative behavior (DRA) procedure effectively reduced those behaviors while compliance to a self-care acquisition task increased markedly. The results are discussed in terms of the importance of determining behavioral function prior to treatment. PMID- 1626085 TI - Review of Behavior on a Disk from CMS Academic Software: instructional programs for teaching teachers. AB - The programs on BOAD represent a set of useful simulations and demonstrations of learning phenomena that successfully convey important practical and theoretical information to students. The most successful modules deal with shaping and the selective effect of positive reinforcement on behavior. The range of examples is sufficiently broad to convey the generality of these learning phenomena, but the graphics and particular examples are better suited to the college classroom (for which they were developed and in which they have received extensive field testing) than to the general public, where some users might be distracted by working with simulated animal "subjects" or bored by the simple graphics. There is a separate application on the disk that drills students on behavioral vocabulary, a useful resource for helping to assure that behavioral issues are discussed using consistent terminology. Although a single disk is initialized for a single user so that individual progress can be tracked accurately in printed reports, the cost of a disk is so low that no student who needs to learn about teaching would be discouraged from purchasing it. In truth, this is the best deal in instructional software I have seen yet. PMID- 1626086 TI - [The April Report and its medical implications]. PMID- 1626087 TI - [The early prognostic assessment of heat stroke]. AB - We study the clinical characteristics of 21 heat strokes at admittance, to analyze the clinical features in relationship with prognosis. 15 patients (71%) suffered a classical heat stroke and 6 (29%) an active heat stroke. Global mortality was 33%. Sun exposition was more frequent in patients who survived (p less than 0.05), fact that we relate with earlier withdrawal from noxa. Patients with worse prognosis were showing more frequently coma (p less than 0.05); photomotor (p less than 0.01), oculocephalic (p less than 0.01) and corneal (p less than 0.01) reflexes abolition; together with disorders in spontaneous and induced motility of members (p less than 0.05); areflexia (p less than 0.01) and plantar extensor response (p less than 0.05). However the most discriminatory parameter between the two groups was the response to cooling, because the outcome was always fatal when cooling did not take place (p less than 0.01). From the analytical standpoint, serum bicarbonate was lower in the patients who died (p less than 0.05). We insist in the need to start prevention and treatment programs in those communities with high incidence of this syndrome. PMID- 1626088 TI - [A Staphylococcus haemolyticus study in urinary infections. An analysis of 8 cases]. AB - Urinary infections caused by Staphylococcus are attributed usually to Staphylococcus epidermidis or Staphylococcus saprophyticus. 8 cases of urinary infection due to S. haemolyticus are discussed: 5 adults all of them over 66 years, diagnosed respectively of diabetes, cancer and stroke. Three children diagnosed of febrile syndrome, encephalopathy and enterocolitis associated with urinary infection. S. haemolyticus was identified through the determination of 19 biochemical parameters. The antibiograms performed showed that all S. haemolyticus isolated were sensible to vancomycin, nitrofurantoin and trimethoprim/sulfamethoxazole. It is concluded that S. haemolyticus is an opportunistic pathogen that is present on immunodepressed hosts, that is why is advisable to perform a more in-depth characterization of the S. epidermidis isolated in urine, especially in persistent pathologic processes. PMID- 1626089 TI - [Humoral immunity following splenectomy in adults]. AB - Humoral immunity was examined in a population of one hundred adult patients splenectomized after abdominal trauma without associated disease, and the results were compared with those observed in healthy individuals. We found, in addition to the disorders, a large increase in the seric concentration of total IgE, and increased presence of autoantibodies and circulating immunocomplexes. These alterations were not correlated with the asplenia period. PMID- 1626091 TI - [Acute suppurative thyroiditis and Klebsiella pneumoniae sepsis. A case report and review of the literature]. AB - The acute suppurative thyroiditis is a rare infection. It affects specially patients with preexisting thyroid gland pathology and its frequency is higher in women. In childhood it's linked to local anatomic defects. The infection used to be located in left thyroid lobe and it's much less usual in right lobe, in both or in isthmus. The most important causal microorganisms are staphylococci (Staphylococcus aureus overcoat) and streptococci (usually Streptococcus pyogenes and Streptococcus pneumoniae), with frequent isolation of mixed flora and anaerobes in the last reported cases. We present the case of a male patient, without previous thyroid disease, who suffered an acute suppurative thyroiditis and Sepsis due to Klebsiella pneumoniae, with right lobe abscess and secondary septic focus formation (kidneys, spleen, lungs), with fatal course despite of medical treatment, favoured or precipitated by the development of serious alcoholic abstinence. PMID- 1626090 TI - [Cryptococcosis in AIDS patients: a study of 19 cases]. AB - We discuss 19 cases of infection due to Cryptococcus neoformans diagnosed in 438 AIDS patients admitted to our center (4%). Fourteen of them showed meningitis confirmed by culture of C. neoformans in CSF. Clinical features were rather unspecific and disorders in CSF parameters were non striking. The diagnostic techniques performed with best results were culture of C. neoformans and antigen determination, especially in serum. Survival probability at one year was 75%. Treatment response was good. Treatment with fluocytosine did not seem to provide additional benefits versus amphotericin alone, neither in respect to clinical evolution nor regarding survival probability at one year. Fluconazole has shown effectiveness in maintenance therapy, being not be possible to evaluate it as an acute phase therapy because the low number of cases in which it was studied. It is advisable to follow a suppressive treatment, having found a 10% relapse rate in patients following therapy and a 50% in those who interrupted it. PMID- 1626092 TI - [A 78-year-old man with pain and tumefaction in the right ankle]. PMID- 1626093 TI - [Clinical management]. PMID- 1626094 TI - [Paraneoplastic arthritis as the first manifestation of a hypernephroma]. PMID- 1626095 TI - [An adverse reaction to proglumetacin]. PMID- 1626096 TI - [The tuberculin test]. PMID- 1626097 TI - [Rectal melanoma and von Recklinghausen's disease]. PMID- 1626098 TI - [Acute ascites as an isolated manifestation of an episode of systemic lupus erythematosus]. PMID- 1626099 TI - [Tussigenic crisis, bronchial hyperreactivity and enalapril]. PMID- 1626100 TI - [Pyogenic liver abscess. Its exclusive treatment with antibiotics]. PMID- 1626102 TI - [Visceral leishmaniasis in immunosuppressed patients]. PMID- 1626101 TI - [The cytosolic concentrations of CAM26 and CAM29 in breast tumors classified according to the clinical stage]. PMID- 1626103 TI - Epidemiology of occupational reproductive hazards: methodological aspects. AB - Both male and female workers may be exposed to occupational agents which affect their reproductive processes. Reproductive outcomes are important in their own right, for example teratogenic effects and impaired neurological development. In addition, reproductive impairment may indicate germ cell mutation, which has far reaching implications. Research into reproductive effects is beset with pitfalls. Applying the results of toxicological research may be suggestive, but such extrapolation is very unreliable owing to profound differences in reproductive and/or toxicological mechanisms. Epidemiological data are therefore indispensable. Optimal methods of data collection and study design, comparable with similar studies of other populations, are essential. Otherwise reliable conclusions cannot be drawn, and this is a waste of resources and of the work and cooperation of everyone who participates in the research. In considering study design, the key question is the measurement (or minimally, the accurate description) of exposures, which is more problematic than the ascertainment of reproductive outcome variables. From the viewpoint of exposures, case control studies have the same disadvantage as studies of the general population, that exposures are heterogeneous, and most specific exposures are therefore rare, even in a large study; in addition, measurement is particularly difficult in this situation. Occupationally defined populations have the corresponding advantages of relative homogeneity and availability of data, although even here numerous problems exist, which are well known. Outcomes can be assessed by means of biological or questionnaire-based methods. They are best regarded as complementary, as each has its strengths and weaknesses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626104 TI - Epidemiology of respiratory hazards: recent advances. AB - A bibliographical review of epidemiological studies published over the last five years has led us to individualize the themes that have been the subject of most recent publications (Table I). These research themes are not new, which shows a certain continuity in epidemiological research on the respiratory risks of occupational origin. Few studies are devoted to the identification of unrecognized respiratory risks; nevertheless, the methodology used, the indicators of effects studies contribute to a better knowledge of the respiratory effects of known occupational exposure factors. Among these effects, exposure to asbestos, silica, isocyanates and organic dusts is frequently referred to in most publications. Smoking habits are more and more taken into consideration in these studies. The themes retained and the publications cited here are not exhaustive, and this bibliographical review does not pretend to represent a complete appraisal of recent developments of the epidemiological respiratory risks of occupational origin. PMID- 1626105 TI - Methodological problems of time-related variables in occupational cohort studies. AB - In studies of long-term health effects of occupational exposures it is important that the time patterns of the study exposure and of the relevant confounders should be taken into account in the analysis. The time-related confounders that have been most frequently considered include age at risk, calendar period, duration of employment, length of follow-up, and employment status (active or retired). These factors are related to the healthy worker effect which is more pronounced among active workers, and declines with length of follow-up. Thus, these time-related factors are potential confounders in occupational cohort studies (and in nested case-control studies). It is therefore advisable to routinely control for length of follow-up and employment status, in addition to the usual confounding factors of age at risk and calendar period. However, it should be stressed that this approach will minimise, but not eliminate, confounding due to the healthy worker effect. In particular, direct control for employment status is inadvisable if this constitutes an intermediate variable in the pathway between exposure and disease, and more complex analytical procedures are necessary in such situations. It is also important that the principle exposure under study should also be analyzed in a time-related manner, taking account of the likely induction and latency periods, and the relative etiological importance of exposure intensity, exposure duration and cumulative exposure. The simplest approach is to analyse the cumulative exposure in a time-related manner, and this may suffice when the aim is merely to consider whether or not there is an effect of exposure. However, once it has been provisionally assumed that an effect exists, attention then shifts to understanding the nature of the effect. In this context, the temporal pattern of exposure and outcome can be considered by examining the effects of exposures in specific time windows while controlling for time-related confounders, and for the effects of exposures in other time windows. A more sophisticated approach is direct fitting of a theoretical model of carcinogenesis, such as the Armitage-Doll or Moolgavkar models. However, it should be emphasized that occupational cohort studies only rarely have sufficient numbers, and data of sufficient quality, to permit meaningful conclusions to be drawn from more sophisticated analyses of this type. PMID- 1626106 TI - Electromagnetic fields and cancer risks. AB - Cancer was first associated with exposure to electromagnetic fields (EMF) in 1979 when Wertheimer and Leeper reported that children dying from cancer resided more often in homes believed to be exposed to higher EMF than did healthy control children. The risks were as high as 2.23 (1.56-3.18) 3.09 (1.68-5.71) for all cancers, 2.98 (1.72-5.15) for leukemia and 2.40 (1.08-5.36) for brain cancers. Wire configuration around houses was used as a surrogate for direct EMF exposure measurements. Wertheimer's finding of an association between cancer and wire configuration around houses has been replicated in two recent studies. However, direct measurement of EMF fields in houses of cancer children have not yielded the same results as the wire configuration around houses, thereby jeopardizing the hypothesis of an association between EMF and cancer. To comprehend the putative association between residential exposure to EMF and childhood cancer, one would have to understand what is hidden behind the notion of 'wire configuration' around the house. In parallel with residential studies, scores of studies were conducted among workers occupationally exposed to EMF. What have we learned from these occupational studies? Hypotheses generating and case control studies have revealed the existence of an excess risk of leukemia among electrical workers. Pooled results have estimated the risk for all leukemia to be 1.18 (1.09-1.29) and for acute myeloid leukemia 1.46 (1.27-1.64). An increased risk of leukemia among electrical workers does not necessarily mean that EMF is a causal agent, other chemicals such as benzene, creosote, solvent, could possibly account for it but this has yet to be confirmed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626107 TI - Uses of biochemical and biological markers in occupational epidemiology. AB - The use of biochemical or biological markers is increasing in cancer epidemiology, but the rationale for their introduction is not always clear, i.e. it has not been established when and how their use is scientifically justifiable, ethically correct and cost-effective. There is an entire range of indications for biomarkers, from the use of very specific measurements aimed at single molecules, to measurements indicating cumulative exposure to agents with the same mechanism of action. The following are some potential uses of markers in occupational epidemiology: 1) exposure assessment in cases in which traditional epidemiologic tools are insufficient (particularly for low doses and low risks; 2) multiple exposures or mixtures, in which the aim is to disentangle the etiologic role of single agents; 3) estimation of the total burden of exposure to chemicals having the same mechanistic target; 4) investigation of pathogenetic mechanisms; 5) study of individual susceptibility (e.g. metabolic polymorphism, DNA repair). Examples are discussed together with methodological limitations. PMID- 1626108 TI - Epidemiology of occupational neurobehavioural hazards. Methodological experiences from organic solvent research. AB - Neurobehavioral hazards have been identified since long in occupational health, e.g. lead, mercury, certain solvents, and many others agents. There are reviews and books on "Occupational neurology" or "Prevention of neurotoxic illness in working populations". Many methods have been applied for studies of the central and peripheral nervous systems in humans: registered diagnoses, questionnaire ratings, clinical evaluation, psychometric tests, neurophysiological and neuroradiological methods, cerebrospinal fluid components etc. Some neurological disorders are well defined, while neuropsychiatric syndromes often are less precisely diagnosed. Decreased subclinical test results in exposed groups might predict an increased risk for later, more serious disorders but the longitudinal information on clinical importance is often lacking. Some historical lessons from the epidemiology of occupational neurology will be repeated and a few reflections on the suitability of different diagnostic entities for epidemiological research shall be made. Since the beginning of the 1970s' a number of studies from the Scandinavian countries have demonstrated long-term neurobehavioral effects from working conditions with relatively moderate exposure to organic solvents. Similar findings have been verified in studies from some countries outside Scandinavia while other studies have been inconclusive. Those results have caused considerable controversy and have been discussed at international conferences and in scientific journals. Very different outcomes have been investigated in those solvent studies, however, and most studies have had a cross-sectional design with inherent problems. The exposure has been assessed in different ways, e.g. by years of occupation, hygienic measurements of the present working conditions, biological monitoring, retrospective assessments on qualitative or semi quantitative scales. Sometimes single solvent exposures have been studied but most of the studies concern mixtures of solvents from aromatic and aliphatic hydrocarbons. As the designs have varied the exposure assessment has been crude and many different outcomes have been studied, it is hardly surprising that the results and the interpretations have differed. The first results from a comprehensive investigation on 135 solvent exposed painters and 71 carpenters as referents, selected from active members of the respective trade union 1965-70 and investigated in the late 80s, will be presented. Clinical, including psychiatric, diagnostic work up and neuropsychological as well as neurophysiological tests have been performed. Psychological test results from military conscripts at age 19 were available for all. The individual exposure history has been carefully assessed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1626109 TI - [An autopsy study of patients who died at the Medical Clinic of the University of Siena from 1986 to 1989]. AB - In the past twenty years autopsies are performed much less frequently in the elderly than in younger patients. The clinical diagnostic error rate documented by autopsy studies ranges from 6% to 68%. We analyzed the clinical and autopsy records of 214 patients who died from 1 January 1986 to 31 December 1989 at our Institute to determine the accuracy of clinical cause of death with respect to the pathologic cause of death. The most common cause of death were bronchopneumonia (25.2%) followed by gastroenteric and lung cancer (20%), cerebrovascular accident (15.8%), myocardial infarction (8%) and pulmonary embolism (7.4%). Pulmonary embolism was correctly classified only in 25% of patients. The most accurately diagnosed condition were neoplastic diseases (88%) and cerebrovascular accident (84.8%) while bronchopneumonia were correctly diagnosed antemortem in 72.2% of the patients studied. Our data suggest that advances in diagnostic technology have not reduced the value of the autopsy and that a goal-directed autopsy remains a vital component in the assurance of good medical care. PMID- 1626110 TI - [The relationships between the lipoprotein profile and rheological-coagulation parameters in patients with hyperlipoproteinemia type II]. AB - The aim of the study was to evaluate the direct influence of lipid parameters (total and HDL-cholesterol, triglycerides and total lipids) on the rheologic coagulative pattern. We studied blood rheological properties--blood (BV), plasmatic (PV), and seric (SV) viscosity, whole blood (WBF) and red cell (RCF) filterability--and some coagulative factors--fibrinogen (Fib), levels of clotting factor VII (fVIIc) and VIII (fVIIIc) activity--in 156 men aged 40-54 years; 87 patients had type II hyperlipoproteinemia (46 type IIa and 41 type IIb) and 69 were normolipemic controls. Smokers, patients with arterial hypertension, diabetes mellitus or cardiovascular clinical manifestations were excluded. Type IIb hyperlipoproteinemic patients had increased blood viscosity (shear rate 225 sec-1, p. less than 0.01), which was positively correlated with triglycerides and fibrinogen concentration. Levels of fibrinogen, fVIIc and fVIIIc activity did not differ significantly in hyperlipemic patients and controls, although fVIIc activity and fibrinogen were both positively related with lipid parameters. These data suggest that, in absence of other major risk factors, the alterations of the rheologic-coagulative pattern are mainly dependent on the severity of the lipid disorder. PMID- 1626111 TI - Hyperosmolar hyperglycemic nonketotic coma in Waldenstrom's macroglobulinemia associated with type II diabetes and complicated by pulmonary tuberculosis. AB - In this paper we describe a successfully treated case of hyperosmolar hyperglycemic non ketotic coma (HHNC). The HHNC was observed in a patient affected by Waldenstrom's macroglobulinemia, associated with type II diabetes and complicated by pulmonary tuberculosis. Hyperosmolar hyperglycemic nonketotic coma is a clinical condition with a high mortality rate associated with a severe increase in blood viscosity. This increase in blood viscosity justifies several clinical manifestations of the HHNC. We believe that an increase in the blood viscosity produced by the simultaneous presence of the single diseases mentioned above may have encouraged the development of hyperosmolar coma in the case reported. PMID- 1626112 TI - [Jaccoud's postrheumatic arthritis. A clinical case report]. AB - The authors describe a case of Jaccoud's arthropathy, a very rare disease of unknown pathogenesis, that can develop in patients after repeated attacks of rheumatic fever. Clinical pictures with analogous features can be found associated with many other pathological processes, such as connective tissue diseases or cancers. The case presented here is interesting for the diagnostic and therapeutic mistakes made, probably because it is an illness very little known and with ambiguous clinical features. PMID- 1626113 TI - [Polymyalgia rheumatica and malignant neoplasms. A report of 3 cases]. AB - Polymyalgia rheumatica (PMR) is an inflammatory disease which mainly affects elderly patients and is highly responsive to steroid therapy. PMR can be associated with giant cell arteritis and, less frequently, with malignancy. The authors describe three cases of paraneoplastic PMR. In one patient PMR has been the initial manifestation of a B-cell non-Hodgkin lymphoma, in two of a malignant neoplasm of the gastrointestinal system. In two patients the response to steroid therapy was documented. A careful clinical evaluation and a long term follow-up is needed before considering PMR an idiopathic disease. PMID- 1626114 TI - [The nonspecific bronchial stimulation test with methacholine and an ultrasonic mist of distilled water: which is to be preferred in the military sphere?]. AB - The authors compare the methacholine (Mch) and the nebulized ultrasonic distilled water (NUDW) bronchial challenge as regard sensitivity and time required to perform them. For military service fitness, were studied 24 asthmatic patients. Each subject performed random a bronchial challenge by Mch (Yan method) and by NUDW (Allegra method) in two different days; for each bronchial challenge has been measured the time required to perform it. The atopic status has been evaluated by skin-prick test. All the subjects have shown a positive response to Mch test (PD 20 FEV1 mean: 352 mcg, range 80-850) whereas 13 subjects (54%) have shown a positive response to NUDW. The time required to evaluate all the subjects by Mch test has been 199.5 minutes whereas the total time required to evaluate all the subjects by NUDW test (127 minutes) and to evaluate by Mch test the non responders to NUDW (100 minutes) has been 227 minutes. The most of subjects were skin reactors. No difference was found as regard onset of disease, basal lung function and atopic status between responders and non responders to NUDW test. We conclude that NUDW test has shown a lack of sensitivity in this sample (50% of asthmatic patients could be misdiagnosed) and that the Mch test is preferable to determine a rapid method for measurement of bronchial responsiveness. PMID- 1626115 TI - [The role of clinical, biochemical and echographic data in identifying the biliary pathogenesis of acute pancreatitis]. AB - The role of clinical (biliary pain and/or jaundice), laboratory (discriminant function (DF) calculated using AST, ALT, AlkPh and GGT serum values) and ultrasonographic (US)(dilation and/or stone of common bile duct (CBD)) findings in identification of the biliary etiology of acute pancreatitis (AP) was studied in 60 patients. AP biliary etiology was defined by ERCP executed in the early phase of the disease (lithiasis and/or stenosis of CBD; endoscopic features of forced papilla in patients with gallstone). US showed the best values of sensitivity (84.6%) and diagnostic efficacy (76.7%); DF showed the best results of specificity (62.5%) and of test positive predictive value (92.8%). The statistical evaluation (McNemar test) showed a significant increase of sensitivity for US vs clinical findings and of specificity for DS vs clinical findings (p less than 0.05). The sensitivity, specificity, accuracy, test negative and positive predictive value were improved to 96.1, 87.5, 96.6, 77.1 and 92% by the combination of US and DF. Therefore the association of US and DF can provide the best non invasive method in rapidly detecting CBD pathology as an etiological factor in AP and then the enough accurate indication to early operative ERCP. PMID- 1626116 TI - [The clinical implications of the use of an amino acid mixture without tryptophan in liver cirrhosis]. AB - The ingestion of an amino acid mixture lacking tryptophan causes a rapid fall of plasma tryptophan in healthy subjects. This is because amino acids elicit protein synthesis and endogenous tryptophan is incorporated into new proteins. If protein synthesis is the mechanism through which tryptophan-free solution decrease blood tryptophan, it may be interesting to study tryptophan levels after a tryptophan free mixture in subjects with impaired protein synthesis. In the present paper we show that in 27 cirrhotics the administration of a tryptophan-free solution caused a fall of total plasma tryptophan that began significantly later than in 14 control subjects, the delay being significantly proportional to the severity of the disease. The difference between control and cirrhotic subjects was due to the bound fraction of plasma tryptophan. The diagnostic and clinical usefulness of our findings are discussed. PMID- 1626117 TI - [The dietary protein contribution and hepatic encephalopathy in cirrhosis]. AB - Hepatic encephalopathy is a neuropsychiatric syndrome, which can occur in the clinical course of acute (fulminant) or chronic hepatic failure of various aetiology; reversible metabolic abnormalities without neuronal structural changes are frequently found in this condition. High blood ammonia levels, an imbalance between plasma concentrations of branched-chain and aromatic amino acids, false neurotransmitters and neurotransmitters receptor changes in CNS are the commonly recognized pathogenetic mechanism of this syndrome. Protein malnutrition is a frequent occurrence in liver cirrhosis, especially of alcoholic aetiology. High protein diets may precipitate hepatic encephalopathy; protein restriction leads to malnutrition and enhances a negative nitrogen balance. Several clinical studies have shown that vegetable proteins are tolerated better than animal in patients with liver cirrhosis and chronic portal-systemic encephalopathy: encephalopathy index is usually lower after vegetable-protein than animal-protein diet. The favourable therapeutic effect of vegetable diets on nitrogen metabolism can be mainly accounted for by the increased intake of dietary fibers and increased incorporation and elimination of nitrogen in fecal bacteria. Mixture of amino acids enriched with branched-chain amino-acids may contribute to maintain a positive nitrogen balance and minimize muscle wasting in cirrhotics. PMID- 1626118 TI - Prenatal diagnosis of inherited hemoglobinopathies. AB - This paper reviews the techniques presently available for the prenatal diagnosis of inherited hemoglobinopathies. At the present time, mutations of the globin genes are detected directly in trophoblast DNA, enzymatically amplified by polymerase chain reaction. Known mutations may be defined by restriction endonuclease digestion, non denaturing gradient gel electrophoresis, allele specific oligonucleotide probes or allele specific oligonucleotide primers. Unknown mutations are detected by denaturing gradient gel electrophoresis followed by direct sequencing. Other potentially useful methods for unknown mutations are single strand conformation polymorphism analysis and chemical mismatch cleavage analysis. A potential pitfall for all procedures based on analysis of amplified DNA is the coamplification of maternal sequences. This may be avoided by a careful dissection of maternal decidua from fetal trophoblast, by using an amount of chorionic villi not inferior to 5-10 mg and by reducing the number of amplifying cycles to approximately 20. Monitoring the presence of co amplified maternal sequences by the analysis of polymorphic sequences is strongly recommended. Future perspectives consist of preimplantation diagnosis by biopsy of the morula or blastula or ova genotyping by analysis of the second polar body. PMID- 1626119 TI - [Current views of thalassemia intermedia]. AB - Recently the molecular bases of thalassemia intermedia have been elucidated in several populations. In general this attenuated, non-transfusion dependent form of homozygous beta-thalassemia is mainly determined by a) the co-inheritance of deletion alpha-thalassemia; b) the presence of the so-called mild beta thalassemia mutations; and more rarely, c) the inheritance of genetic conditions able to enhance the gamma-globin chain expression in adult life. Although there are several complex genetic and acquired interactions involved in the wide clinical heterogeneity of thalassemia intermedia, data in Italians indicate a definite genotype-phenotype relationship in conditions such as the co-inheritance of at least two alpha-thalassemia genes in severe and mild homozygous beta thalassemia; the molecular homozygosity or double heterozygosity for the -87, 101 and IVS1(nt6) beta(+)-thalassemia mutations; and the coexistence of structural gamma-globin gene defects, i.e. Sicilian and Sardinian delta beta thalassemias, deletional and non-deletional hereditary persistence of fetal hemoglobin and the polymorphism for the -158 XmnI G gamma restriction site. Thalassemia intermedia resulting from the inheritance in heterozygous beta thalassemia of triple alpha-globin gene complex or the presence of dominant beta thalassemia is also described and the role of these new informations in genetic counselling is discussed. PMID- 1626120 TI - Transient monocular blindness in a patient with giant-cell arteritis. Pathogenetic and therapeutic considerations. PMID- 1626121 TI - Postoperative elevations of serum interleukin 6 and group II phospholipase A2: group II phospholipase A2 in serum is an acute phase reactant. AB - Elevations of serum immunoreactive interleukin 6 (IL-6) and Group II phospholipase A2 (M-PLA2) were observed without exception after elective surgeries for various sites. Serum IL-6 rose steeply after surgery, and reached the maximum level on the 1st postoperative day. Serum M-PLA2 increased from the 1st postoperative day and reached the maximum level on the 2nd postoperative day in 10 patients (76.9%), on the first day after surgery in 2 patients and on the 3rd day in one patient. The peak serum M-PLA2 after surgery was significantly correlated with the peak IL-6 and blood loss volume during surgery. These results suggested that serum M-PLA2 is an acute phase reactant. PMID- 1626122 TI - Enhanced mobilization of hepatic cadmium in mice upon coadministration of an N, N disubstituted dithiocarbamate and an alkyl monoester of dimercaptosuccinate. AB - Oral (po) administration of mono-iso-amyl (2,3-dimercapto) succinate (Mi-ADMS), 0.5 mmol/kg for three consecutive days, to mice previously injected with cadmium (Cd) chloride reduced the whole body Cd burden 34%. Intraperitoneal (ip) administration of N-iso-amyl-N-glucaminedithiocarbamate (i-AmGDTC) by the same regimen reduced total body Cd 41%. Coadministration of the two compounds reduced the whole body Cd burden 60% (p less than 0.05). The liver Cd concentration was reduced 56% and 50%, respectively, by Mi-ADMS given po and i-AmGDTC given ip, each at 0.5 mmol/kg for three consecutive days. Coadministration of the two chelators reduced the liver Cd concentration 90% (p less than 0.05). The kidney Cd concentration was reduced 10% by Mi-ADMS alone, and 60% by i-AmGDTC alone, but there was only a 47% reduction when the two chelators were coadministered, probably as a result of redistribution of mobilized hepatic Cd to the kidneys. As 50-55% of the administered Cd is sequestered in the liver in this mouse model, it is concluded that coadministration of the two chemical classes of Cd complexing agents may offer a therapeutic advantage over administration of either agent alone. PMID- 1626123 TI - Enantiomeric interaction in the sulfate conjugation of the beta 2-agonist drug albuterol by the human liver. AB - Sulfate conjugation of the pure enantiomers of albuterol was compared to that of racemic drug using the 100,000g cytosol of four human livers as the catalyst. Whereas a trend towards a lower Kmapp was seen for sulfation of (-)-compared to (+)-albuterol, there was no enantiomeric difference in Vmaxapp. However, when the sulfation of racemic albuterol was compared to that of its pure enantiomers, there was a marked suppression of the reaction. This was due to a reduction in Vmaxapp by about 75% (p less than 0.01) with no difference in Kmapp. Thus, an enantiomeric interaction occurs in the sulfoconjugation of albuterol, which must be taken into account when evaluating the pharmacokinetics of the individual enantiomers following racemic drug administration. PMID- 1626124 TI - Nephrotoxicity of thiazoles structurally related to thiabendazole in mice depleted of glutathione by treatment with buthionine sulfoximine. AB - In mice depleted of glutathione (GSH) by treatment with DL-buthionine sulfoximine (BSO), thiabendazole [2-(4'-thiazolyl)benzimidazole, TBZ] produces renal damage characterized by increases in relative kidney weight and serum urea nitrogen (SUN) concentration. Several thiazole and benzimidazole compounds related to TBZ were examined for the ability to cause nephrotoxicity in mice pretreated with BSO. 4-Methyl- and 4-phenylthiazoles were highly effective compounds. In the absence of BSO, 4-methylthiazole resulted in no nephrotoxicity; inhibitors of hepatic and renal cytochrome P-450 enzymes such as methoxsalen and piperonyl butoxide prevented the nephrotoxicity of 4-methylthiazole given in combination with BSO. In addition, there was a sex difference in the nephrotoxicity of 4 methylthiazole in combination with BSO; the nephrotoxicity was observed only in males. These features of nephrotoxicity of 4-methylthiazole are well in accord with those of TBZ previously reported. This suggests that TBZ and 4 methylthiazole share a common mechanism of nephrotoxicity. PMID- 1626125 TI - Influence of a combination of ritodrine and nifedipine on the isolated rat uterus. AB - Studies were undertaken to evaluate the efficacy of the beta 2-adrenergic agonist ritodrine and the calcium channel blocker nifedipine, alone and in combination, for inhibition of contraction in isolated rat uterine strips. Both compounds produced a dose-dependent reduction of area under the curve. When contractions were produced by oxytocin, a 26% reduction was observed with 0.144mcg of ritodrine and a significant 68.1% decrease was produced with 1.44mcg of ritodrine. Contraction frequency (contractions per ten minutes) was not significantly affected. Prostaglandin F2 alpha-induced contractions were significantly inhibited 27.1% and 62.2% by 1.44mcg and 14.4mcg of ritodrine, respectively. Also, contraction frequency was significantly affected by both concentrations. Inhibition of area under the curve of oxytocin-induced contractions produced by nifedipine was 39.3% for 0.05mcg and 78.4% (P less than 0.05) for 0.50mcg. Contraction frequency was unaffected. Prostaglandin F2 alpha induced contractions were significantly attenuated by 60% and 86% with nifedipine (0.50mcg and 5.02mcg, respectively); contraction frequency was significantly reduced from 15 to 2 contractions per ten minutes by 5.02mcg. Oxytocin-induced contraction was attenuated 39.8% by a combination of ritodrine 0.144mcg and nifedipine 0.05mcg; contraction frequency was unaffected. Area under the curve and contraction frequency of oxytocin-induced contractions were significantly decreased by a combination of ritodrine 0.144mcg and nifedipine 0.50mcg (89.8% reduction; decrease in frequency from 12 contractions in control to 4 contractions post-inhibitory agent). Significant attenuation of prostaglandin F2 alpha-induced contractions was produced by ritodrine 1.44mcg and nifedipine 0.50mcg. Area under the curve decreased by 73.2% and frequency was reduced from 13 to 8 contractions. A combination of ritodrine 1.44mcg and nifedipine 5.02mcg also produced significant decreases in area under the curve (85.3%) and frequency (13 contractions in control to 1 contraction after compounds were added). Because the mechanisms of action of these two agents are different, it is reasonable to suggest that they be used in combination to control premature labor. The results of this study suggest they may provide inhibition of contraction superior to either agent alone, and could therefore provide more effective inhibition and possibly reduce untoward side effects common to ritodrine therapy. PMID- 1626126 TI - Effect of fenofibrate on the tail artery contraction of rats fed with an atherogenic diet. AB - The feeding of rats by an atherogenic diet for 4 weeks modified the postsynaptic effect of noradrenaline in the perfused rat tail artery. When fenofibrate (100 mg/kg p.o.) was administered simultaneously, with an atherogenic diet, at the first onset of the experiment this effect was completely inhibited, while when it was administered from the 15th day of the experiment it had no effect on vasoconstrictor responses to noradrenaline. The atherogenic diet decreased the contraction of the rat tail artery at the lower concentrations (3 x 10(-8) - 3 x 10(-7) M) and increased vasoconstrictor response to a maximal concentration (10( 5) M) of noradrenaline. These results suggest that fenofibrate can prevent the changes in the contractile profile of an isolated atherogenic rat tail artery. PMID- 1626127 TI - Modulation of hepatic and pulmonary drug-metabolizing enzyme activities of rabbits by dietary cholesterol. AB - Modulation of the activities of drug-metabolizing enzymes by dietary cholesterol was studied in rabbits. In male rabbits fed a 1.5% cholesterol-diet, an elevated levels of serum cholesterols and triglycerides were observed from the early phase of cholesterol-feeding. At 12 weeks after the onset of cholesterol feeding, a marked increase was observed in the wet weights of livers but not of lungs, while total contents of lipids and cholesterols were elevated in both tissues in cholesterol-fed animals. The content of collagen was increased significantly in livers, but not in lungs and the phase I drug-metabolizing enzyme activities were significantly reduced in livers but remained unchanged in lungs by cholesterol feeding. On the other hand, the phase II drug-metabolizing enzyme activities varied depending on the enzymes in both tissues. The results demonstrate that dietary cholesterol induces different effects on rabbit liver and lung and that the modulation of the hepatic enzymes by dietary cholesterol in rabbits differs from that in rats, mice and guinea pigs in which the activity of the enzymes are elevated by dietary cholesterol. PMID- 1626128 TI - Effects of 2,5-dimethylpyrazine on reproductive and accessory reproductive organs in female rats. AB - The effects of 2,5-dimethylpyrazine on reproductive and accessory reproductive organs in female rats were studied. Following the administration of 2,5 dimethylpyrazine, uterus weight was significantly decreased while ovary weight was not affected, nor was there any influence on serum level of estradiol. The increase of uterine weight observed following estradiol injection after ovariectomy was inhibited by 2,5-dimethylpyrazine pretreatment. The uptake of 3H estradiol into the uterus was also significantly decreased by 2,5 dimethylpyrazine. On the other hand, chlorpromazine administration resulted in significant decrease in ovary and uterus weight as well as serum estradiol level. These results suggest that 2,5-dimethylpyrazine may have direct inhibitory action on the uterus of rats. PMID- 1626129 TI - CO uptake kinetics of red cells and CO diffusing capacity. AB - The rate at which CO displaces oxygen from combination with hemoglobin in intact red cells was measured spectrophotometrically in whole blood thin films that minimize unstirred layer extra-cellular diffusion barriers. A step-change was made in CO tension from zero to one of four values (2, 7, 21 and 70 Torr) during a constant background of one of eight O2 tensions (0, 40, 70, 100, 153, 214, 285 and 428 Torr). For PO2 greater than 100 Torr measured red cell initial CO uptake rates were compared with calculated rates at the same PCO-PO2 based on the Gibson Roughton rate equation (Gibson and Roughton, Proc. R. Soc. B 143: 310-334, 1955) for a well mixed Hb solution. Measured CO uptake rates expressed as initial rate of saturation change (delta S/delta t) quantitatively followed the theoretical rate equation (time in seconds) [sequence: see text] These measurements provide new values for theta CO, the specific conductance of whole blood (ml.min-1.Torr 1; PCO, PO2 in Torr): [sequence: see text] These results signify that in vivo, in normoxia and hyperoxia, red cell CO uptake rate is wholly reaction rate limited and that pulmonary capillary red cell CO diffusion equilibrium is rapidly achieved. The Bohr-Krogh assumption that red cell PCO = 0 during CO uptake is untrue. PMID- 1626130 TI - Ventilation and gas exchange during sustained exercise at normal and raised CO2 in man. AB - Five subjects underwent each of three protocols for 43 min: (A) at rest; end tidal PCO2 was held constant at 2-5 Torr above resting values; (B) during 70 Watt bicycle exercise; PETCO2 was uncontrolled; (C) during 70 Watt exercise; PETCO2 was held 2-5 Torr above exercising values. During all protocols, end-tidal PO2 (PETO2) was held at 100 Torr. The first 5 min of each protocol were excluded from data analysis to approach a steady state, and the remaining 38 min analysed to determine whether any trends were present. At rest, ventilation did not change over the 38 min period. However, during hypercapnic exercise (protocol C), ventilation rose significantly by a mean +/- SE of 4.9 +/- 0.8 L/min (P less than 0.01) over the 38 min period. In protocol B, ventilation was lower than in protocol C, but did not change over the 38 min period. However, PETCO2 fell significantly by a mean of 0.65 +/- 0.05 Torr (P less than 0.01). This change in PETCO2 was due to a significant fall in the respiratory quotient (mean = -0.05 +/ 0.01, P less than 0.01) and metabolic CO2 production (mean = -0.06 +/- 0.01 L/min, P less than 0.01). The fall in respiratory quotient implies a change in metabolic substrate during exercise. Furthermore, the results suggest that ventilation is not always matched closely to metabolic CO2 production during exercise. PMID- 1626131 TI - Functional characteristics of arterial chemoreceptors in an amphibian (Bufo marinus). AB - In order to further describe the functional characteristics of arterial chemoreceptors of anuran amphibians, multi-unit chemoreceptor discharge frequency (MCDF) was recorded from the carotid (N = 23) or aortic nerve (N = 2) of pithed, unidirectionally ventilated toads (Bufo marinus). MCDF increased with decreasing PaO2: typically, the threshold PaO2 lay between 40 and 60 mmHg. The MCDF-PaO2 relationship was right-shifted along the PaO2 axis by increasing PaCO2 (N = 5). In three toads, the MCDF-PaO2 relationship was unaffected when CaO2 was reduced 35-89% by hemorrhage. MCDF was also unaffected by occlusion of the outflow from the heart, though it increased upon release of the occlusion. MCDF was stimulated by epinephrine, and inhibited by dopamine. Our results demonstrate that the MCDF responds to the range of PaO2 and PaCO2 values encountered in vivo, suggesting that arterial chemoreceptors may participate in ventilatory control in toads. The receptors do not respond to the rate of oxygen delivery per se, and may be influenced by catecholamines known to exist in the carotid labyrinth. PMID- 1626132 TI - Effects of endothelin, platelet activating factor and thromboxane A2 in ferret lungs. AB - We have compared the effects of three vasoactive agents, endothelin, platelet activating factor and thromboxane A2 analogue, U 46,619, in the pulmonary circulation of ferrets. Lungs of nine adult ferrets, body weight 1.06 +/- 0.27 kg, were isolated and perfused with sheep red blood cells suspended in Kreb's solution with 2 g% Dextran 70 (hematocrit 33 +/- 6%), under conditions of constant flow in zone 3. Endothelin-1 (ET: 0.1-1.35 micrograms/kg), platelet activating factor (PAF: 0.5-5.5 micrograms/kg) or thromboxane A2 analogue (U 46,619: 1 microgram/kg), was infused into the pulmonary artery and the pressure response determined. To locate the site of action of the agents, the pulmonary circulation was partitioned into arteries, microvessels and veins by measuring pressures in 20-50 microns diameter subpleural arterioles and venules by micropuncture, both during baseline and after the peak response to each vasoactive drug. We found that the ferret pulmonary circulation constricted in response to ET, PAF and U 46,619, but the magnitude of constriction varied. Ferret lungs were most sensitive to U 46,619 and least sensitive to PAF. The major site of action also differed among the agents; U 46,619 and ET predominantly constricted veins whereas PAF predominantly constricted arteries. We conclude that the ferret pulmonary circulation demonstrates differential responsiveness to vasoactive agents, that venous constriction is a common feature and that the predominant site of action varies with the specific agent. PMID- 1626133 TI - Strength of the pulmonary blood-gas barrier. AB - The mammalian pulmonary blood-gas barrier is well known to be extremely thin. For example, in the human lung, half of the area of the barrier (the 'bulging' part) has a thickness of only 0.2-0.4 micron. We show here that the barrier is also immensely strong. This is an essential requirement because the capillary wall stresses during heavy exercise become very large (about 7 x 10(4) N/m2 = 70 kPa) when capillary pressure increases to 30 mmHg. Stress failure of the pulmonary capillary wall consistently occurs in experimental rabbit preparations at abnormally high pressures exceeding 40 mmHg and may be the cause of bleeding into the lung in galloping racehorses. The great strength of the thin side of the blood-gas barrier can be attributed to the extracellular matrix, especially the type IV collagen which is predominantly located in the very thin lamina densa. The alveolar wall is therefore particularly vulnerable to injurious agents which attack type IV collagen such as autoantibodies in Goodpasture's Syndrome and perhaps neutrophil elastase in emphysema. The combination of extreme thinness and great strength of the blood-gas barrier poses a unique design requirement. PMID- 1626134 TI - P-V characteristics in heart-pulsation affected and non-affected lung units: a model. AB - Elastic recoil pressure, pleural pressure and pressure pulsation of the heart (PHRT) control the expired flow from a small lung unit. Variability in each trait may affect the expirate. The same (SDPV) or different (DDPV) regional distribution of P-V characteristics, regional effects of PHRT-affected (O) and non-affected units (N) and regional differences in pleural pressure, were incorporated into a computer model. Output acceptability was judged by the alveolar slope of the N2 washout, cardiogenic oscillations (CO) and the phase shift between PHRT and CO. Can SDPV be in both O and N units? What causes CO and phase shift? With SDPV in O and N units, CO were negligibly small. The incorporation of the pleural pressure difference did not fulfill the three criteria, which were met when there was DDPV in the N and O units. We conclude that the distribution of P-V characteristics changes with the distance from a pulsating artery, and only DDPV, and not different time constants or pleural pressure difference, can explain CO. PMID- 1626135 TI - Estimating alveolar surface area during life. AB - Alveolar surface area (Sa) may be derived from measurements of total lung capacity (TLC) and mean linear intercept (Lm), an estimate of average airspace size. Because the index of pulmonary distensibility, K, is a function of Lm, we were able to derive Lm from ln K using their respective age regressions and estimated Sa in 147 healthy subjects. K was obtained from exponential analysis of static pressure-volume data. TLC was measured in a body plethysmograph. As an estimate of airspace size, the value used for Lm was shown to be appropriate for the air-inflated lung at TLC. In 95 men (mean age 40 +/- 16 SD years), Sa was 118 (SD 22) m2 and in 52 women (mean age 38 +/- 17 SD years) it was 91 (SD 18) m2 and Sa decreased with age (P less than 0.001). In a morphometric study, Thurlbeck (Am. Rev. Respir. Dis. 95: 765-773, 1967) obtained smaller values for Sa (owing to the use of a smaller lung volume) and a similar decrease in Sa with age as that found here. Providing a standardised methodology is used for measurement of K, the present method allows a reasonable estimate of Sa to be obtained during life. PMID- 1626136 TI - Influence of exercise training on the oxidative capacity of rat abdominal muscles. AB - Our purpose was to determine if endurance exercise training would increase the oxidative capacity of the abdominal expiratory muscles of the rat. Accordingly, 9 male rats were subjected to an endurance training protocol (1 h/day, 6 days/week, 9 weeks) and 9 litter-mates served as controls. Citrate synthase (CS) activity was used as an index of oxidative capacity, and was determined in the following muscles: soleus, plantaris, costal diaphragm, crural diaphragm, and in all four abdominal muscles: rectus abdominis, transversus abdominis, external oblique, and internal oblique. Compared to their non-trained litter-mates, the trained rats had higher peak whole body oxygen consumption rates (+ 16%) and CS activities in plantaris (+34%) and soleus (+36%) muscles. Thus, the training program caused substantial systemic and locomotor muscle adaptations. The CS activity of costal diaphragm was 20% greater in the trained animals, but no difference was observed in crural diaphragm. The CS activity in the abdominal muscles was less than one half of that in locomotor and diaphragm muscles, and there were no significant changes with training except in the rectus abdominis where a 26% increase was observed. The increase in rectus abdominis CS activity may reflect its role in postural support and/or locomotion, as none of the primary expiratory pumping muscles adapted to the training protocol. The relatively low levels of CS activity in the abdominal muscles suggests that they are not recruited frequently at rest, and the lack of an increase with training indicates that these muscles do not contribute significantly to the increased ventilatory activity accompanying exercise in the rat. PMID- 1626137 TI - Effect of a single breath of cigarette smoke on slowly adapting receptors in canine lungs. AB - Inhalation of cigarette smoke has been shown to induce bronchoconstriction which should stimulate slowly adapting pulmonary stretch receptors (PSRs). To test this possibility, the activity of PSRs was recorded from fine afferent filaments of the vagus nerve before and after 120 ml of smoke generated from high-nicotine cigarettes was delivered into the lungs in a single breath in anesthetized, open chest and artificially ventilated dogs. The base-line activity of PSRs did not change during the first two breaths following smoke delivery. However, PSR activity started to increase by the third breath (post-smoke), concomitant with an increase in tracheal (transpulmonary) pressure. Both the smoke-induced increase in tracheal pressure and the delayed effect on PSRs were prevented by a pretreatment with aerosolized isoproterenol, a bronchodilator, suggesting that the delayed response of PSRs to smoke was elicited by the change in bronchomotor tone. Although smoke evoked a delayed stimulation in the majority (61%) of the PSRs studied, it caused a mild delayed inhibition (24%) or had no effect (15%) in some of the receptors. The variable responses to smoke among PSRs are probably related to the smoke-induced heterogeneous changes of mechanical properties in the lungs and their different anatomic locations. PMID- 1626138 TI - Oxygen consumption and acid-base balance during shallow hypothermia in the pigeon. AB - In pigeons, during shallow nocturnal hypothermia induced by food deprivation, body temperature falls to values between 35 degrees C and 38 degrees C. Body temperature, oxygen consumption, and arterial blood pH and PCO2 were recorded during the entrance into such nocturnal hypothermic periods. In vivo pH was kept constant, while in vivo PCO2 increased slightly during hypothermia. This caused the temperature-corrected value of pH (pH*, measured at 40 degrees C) to fall by 0.014 units/degrees C, and the total CO2-content to rise by 3.2 mM, an increase of 16%. These changes in the acid-base balance represent, in effect, a respiratory acidosis that closely parallels the normal buffer line for pigeons. Q10 values, relating oxygen uptake to body temperature, were higher than 4.0 at the very beginning of the entrance into hypothermia, indicating that the metabolic rate was actively inhibited. However, the present results do not indicate any relationship between the acidosis and the inhibition of the metabolic rate. PMID- 1626139 TI - Acid-base state and intermittent breathing in the torpid bat, Eptesicus fuscus. AB - The effects of intermittent breathing on acid-base state and blood gases were characterized in the torpid bat, Eptesicus fuscus, during steady-state torpor between body temperatures (Tb) of 5 and 37 degrees C. Arterial blood samples were taken from indwelling catheters without disturbing the torpid state. Arterial pH (pHa) of samples taken without knowledge of ventilatory state rose by 0.15 units from 37 to 5 degrees C with a delta pHa/delta Tb slope over this range of -0.0055 U/degrees C. However, at and below Tb = 20 degrees C, Eptesicus fuscus breathes intermittently with typical apneic periods of 40-150 min and 4-12 min at 10 and 20 degrees C, respectively. Samples taken at the end of a ventilatory bout and near the end of an apneic period at Tb = 20 degrees C revealed cyclic changes in pH (from 7.49 +/- 0.02 to 7.34 +/- 0.01), PO2 (from 96.6 +/- 3.4 to 30.8 +/- 3.9 Torr), and PCO2 (28.2 +/- 1.4 to 45.9 +/- 1.5 Torr). Between 10 and 37 degrees C, end-ventilatory pHa varied inversely with temperature with a delta pHa/delta T slope of -0.011 U/degrees C. Because intermittent breathing is common to many animals during hibernation, these results demonstrate the importance of coordinating blood sampling with ventilatory state for a reliable interpretation of acid-base regulation under these conditions. PMID- 1626140 TI - Ventilatory response to hypoxia and hypercapnia in the torpid bat, Eptesicus fuscus. AB - Ventilatory pattern and ventilatory responses to hypercapnia and hypoxia were investigated in torpid big brown bats at body temperatures of 5, 10, 20, 30 and 37 degrees C. The pattern of breathing at temperatures below 30 degrees C was intermittent, consisting of rhythmic breathing bouts separated by apneic periods with occasional sporadic, non-rhythmic breathing episodes. Overall ventilation (Ve) was matched consistently to overall oxygen consumption (MO2) over the entire range of temperatures with a mean air convection requirement (Ve/MO2) of 1.28 L/mmol. However, calculating the air convection requirement using only oxygen uptake acquired during ventilation yielded an ectotherm-like temperature relationship. Ventilation was stimulated at all temperatures by either increased inspired CO2 or decreased inspired O2. At 20 degrees C, graded hypercapnic stimulation increased the duration of the rhythmic bouts and decreased the duration of apneas until at high CO2 (greater than 3%) breathing was continuous. Hypoxic stimulation below about 7% O2 increased ventilation by selectively increasing the non-rhythmic ventilations and decreasing rhythmic bouts. PMID- 1626141 TI - Pulmonary gas exchange during intermittent ventilation in the American alligator. AB - The present study characterized pulmonary gas exchange in the American alligator, Alligator mississipiensis during ventilation and apnea at a body temperature (Tb) of 25 degrees C. Pulmonary gas exchange parameters were measured on a breath-by breath basis utilizing a computer-assisted data acquisition system. In addition, paired blood samples were analyzed from left and right atrium during ventilation and voluntary apneas (1, 2, 5 and 10 min). Measurements of lung PO2 and PCO2 indicated that as apnea progressed, CO2 flux into the lung decreased rapidly while O2 was continuously removed at a constant and steady rate. The reduction in VCO2 resulted in a decrease in R (less than 0.4). Blood gas measurements indicated that the pulmonary arterial-pulmonary venous PCO2 difference, (Ppa Ppv)CO2 was 4.9 +/- 0.9 mmHg during ventilation, decreased and became negative within 2 min of apnea, reaching -3.9 +/- 0.6 mmHg after 10 min. It is postulated that during apnea the Haldane effect accounts for both the blood gas behavior across the lung and insures a continued CO2 flux into the lung during apnea. PMID- 1626142 TI - Effect of amiloride and surfactant on lung liquid clearance in newborn rabbits. AB - Immature and nearly mature fetal rabbits (gestational age 27.5 and 29.5 days, respectively) were obtained by hysterotomy and tracheotomized at birth. Immature rabbits received, via the tracheal cannula, 2.5 ml/kg of either normal saline, porcine surfactant (60 mg/ml), 1 mM amiloride in normal saline, or a mixture of surfactant and amiloride; nearly mature rabbits received either normal saline, or 1 mM amiloride in saline. The neonates were ventilated with a tidal volume of approximately 10 ml/kg for 0-60 min (immature animals) or 0-120 min (nearly mature animals). The lungs were then excised for determination of wet lung weight/body weight ratio (LW/BW). The right lung was further processed for quantification of extravascular lung water (EVLW) per unit dry lung weight, and the left lung fixed for measuring the size of perivascular 'cuffs' (adventitial tissue including lymphatics) in histological sections, using vascular lumen as reference volume. Immature animals receiving surfactant had improved compliance and smaller perivascular cuffs in comparison with the other groups. In immature animals amiloride had no effect on compliance, LW/BW, and EVLW, but reduced perivascular cuff size at 15 min. Nearly mature animals receiving amiloride had higher values for LW/BW and EVLW at 120 min, and lower perivascular cuff size at 15, 60, and 120 min, in comparison with saline-treated litter-mates. We conclude that surfactant improves lung-thorax compliance and reduces perivascular fluid accumulation in immature newborn animals without influencing total lung water content, and that amiloride retards fetal lung liquid resorption in nearly mature newborn animals without affecting lung-thorax compliance during artificial ventilation. PMID- 1626143 TI - When are resting water-breathers lacking O2? Arterial PO2 at the anaerobic threshold in crab. AB - The minimum arterial O2 partial pressure (PaO2) at which, in resting conditions, O2 consumption (MO2) can be maintained and below which anaerobic metabolism is initiated was studied in the crabs Eriocheir sinensis and Carcinus maenas at 15 degrees C. Arterial PO2, MO2 (in E. sinensis), blood lactate concentration ([lact]b) and blood copper concentration ([Cu]b, an index of the blood O2 carrying capacity) were determined after 24 h exposure to inspired PO2 (PIO2) ranging from 2.7-2.1 kPa. They were compared to normoxic controls. In normoxia, the most frequently measured PaO2 ranged between 1 and 3 kPa in both species. In hypoxia, the threshold for blood lactate appearance was PaO2 = 2.1 kPa in E. sinensis and 1.3 kPa in C. maenas, but in many individuals anaerobic metabolism was initiated at lower PaO2's. The lowest PaO2 with [lact]b approx. 0 was 0.7 kPa in both species. MO2 was maintained in 4 E. sinensis out of 6 with PaO2 ranging from 0.7-1.2 kPa (PIO2 = 2.1 kPa). The arterial PO2 at which anaerobic metabolism occurred was not related to blood O2 carrying capacity. PMID- 1626144 TI - Metabolic responses of chicken embryos and hatchlings to altered O2 environments. AB - The oxygen consumption (MO2) response over a 4 h period of exposure to altered ambient O2 (air, 10, 15, 40, 60, 80 and 100%), helium (He) and sulfur hexafluoride (SF6) environments was determined for young (12 days old) and late (16 and 18 days old) embryos, externally pipped (EP) eggs and just hatched chicks (hatchlings) of the domestic fowl. The young embryos were insensitive to hyperoxic gas mixtures and to He exposure, while the late embryos increase their MO2 in hyperoxic environments, independently of O2 concentration, and also in a He atmosphere. Both the young and late embryos responded to SF6 exposure with decreasing MO2, as SF6 reduces O2 diffusivity through the eggshell. The MO2 of EP eggs and hatchlings in He and SF6 varied very widely, the effects of altered diffusivity being insignificant. In hypoxic environments in which the MO2 decreased, the fall of MO2 became smaller as embryos developed and particularly after they pipped the shell and hatched. In an atmosphere of 10% O2, the MO2 of all embryos in the egg before hatching decreased to below 10% of the control after 4 h, while in hatchlings the MO2 remained above 80% of the control. As all embryos in situ in the egg depend entirely or partly on diffusion in order to obtain O2, this emphasizes the limitation of the diffusive process. A 4 h exposure to 10% O2 was lethal for embryos in the egg even if they had pipped the shell and were breathing air with the lungs. PMID- 1626145 TI - Effect of pulsatile flow on gas exchange in the fish gill: theory and experimental data. AB - A model for gas exchange in the fish gill allowing for time-varying water and blood flow is presented. An analysis based on this mathematical model shows that pulsatile water and blood flow potentially may reduce the efficiency of gas exchange significantly. The degree of inefficiency imposed on gas exchange is, however, determined by the physical dimensions of the gill and the gas capacitance coefficients of water and blood. Using anatomical and physiological data it is shown to be likely that for a large group of fishes, including the salmonids, pulsatility of water and blood flow affects gas exchange efficiency only marginally. A close coupling between cardiac and respiratory rhythms is therefore only of marginal advantage to gas exchange efficiency. Due to their exceptional gill dimensions tunas, and to a lesser extent mackerels, are susceptible to the negative effect of pulsatility on gas exchange, which may be one of the factors favouring ram ventilation in these species. PMID- 1626146 TI - Ventilatory effects of the interaction between phrenic and limb muscle afferents. AB - We studied the effects on ventilation and ventilatory muscle activation of stimulation of the central ends of the left phrenic and gastrocnemius nerves separately and concurrently in 10 spontaneously breathing, alpha-chloralose anaesthetized dogs. The nerves were stimulated for 1 min, at a frequency of 40 Hz and pulse duration of 1 ms. The phrenic nerve was stimulated at 20 and 40 times twitch threshold (TT). During these stimulation periods ventilation increased by 39% and 79% of control values, respectively. The gastrocnemius nerve was stimulated at 20 times TT. This produced a 90% increase in ventilation. Stimulation of either nerve resulted in increases in the activity of the right diaphragm, parasternal intercostal and alae nasi muscles comparable in magnitude to the increase in tidal volume. The activities of the genioglossus and transversus abdominis muscle increased to a much greater extent than did the other muscles under all conditions. In contrast, triangularis sterni activity remained unchanged during stimulation of either nerve. The phrenic nerve was then stimulated at 40 times TT for 1 min with superimposed gastrocnemius nerve stimulation (20 times TT) during the last 30 s. Ventilation had risen by 66% after 30 s of phrenic nerve stimulation. With the addition of gastrocnemius nerve stimulation, ventilation rose by a further 84% for a total increase of 150% of the control value. Mathematical summation of the responses to individual nerve stimulation at these intensities predicted a 156% increase in ventilation. Similar degrees of summation were found with respect to respiratory muscle activation. We conclude that the interaction between phrenic and limb muscle (gastrocnemius) afferent is additive with respect to their effects on ventilation. PMID- 1626147 TI - Thromboxane A2 mimetic, U46,619, and slowly adapting stretch receptor activity in the rabbit. AB - The effect of infusing the thromboxane A2 mimetic U46,619 on afferent activity from slowly adapting airway stretch receptors (SARs) in the anesthetized rabbit was examined in these experiments. SAR vagal afferent fibers (n = 29) were identified by their slow adaptation to a sustained (10-15 s duration) lung inflation in the closed-chest, mechanically ventilated animal (n = 16). Intravenous infusion of U46,619 increased the discharge frequency of the SAR, measured at the end of inspiration, in a dose-dependent manner: by 6.6% and 8.0% at doses of 0.1 and 0.5 microgram of U46,619/kg, respectively. This increase in SAR activity was correlated with increases in end-inspiratory tracheal airway pressure (6.4% at 0.1 micrograms/kg and 9.1% at 0.5 micrograms/kg). Higher doses of U46,619 could not be administered due to decreases in systemic arterial blood pressure. The increase in SAR activity and tracheal airway pressure was qualitatively comparable to the response to histamine (25 micrograms/kg), a known bronchoconstrictor. We conclude that intravenous infusion of U46,619 in the anesthetized rabbit at doses that elicit significant hemodynamic effects causes modest bronchoconstriction and comparable increases (less than 10%) in SAR afferent nerve activity. From these data, it appears that U46,619 has no direct effect on SARs, but rather increases SAR activity due to bronchoconstriction. PMID- 1626149 TI - Normal immune function of the gastrointestinal tract. PMID- 1626148 TI - An assessment of central-peripheral ventilatory chemoreflex interaction in humans. AB - The independence of the central and peripheral chemoreflexes has been tested in humans. Acute metabolic acidosis generated by a prior bout of brief, hard exercise was used to stimulate primarily the peripheral chemoreceptors, and respiratory acidosis generated by inhaled CO2 was used to stimulate both central and peripheral chemoreceptors. Seven healthy young men were studied. Ventilation and arterial pH, PCO2 and PO2 were recorded. Peripheral chemoreflex sensitivity to hypoxia during acute metabolic acidosis was repeatedly determined by measuring ventilation in euoxia (PETO2 = 100 Torr) and hypoxia (PETO2 = 50 Torr) as the subject recovered from exercise-induced acidosis. Peripheral chemoreflex sensitivity to hypoxia during CO2 inhalation was repeatedly determined by measuring ventilation in euoxia and hypoxia at two levels of hypercapnia (PETCO2 = 45 Torr and PETCO2 = 50 Torr). The ventilatory sensitivity to hypoxia at matched arterial pH values was not significantly different between conditions of high (CO2 inhalation) and low (metabolic acidosis) central chemoreceptor activity. We therefore conclude that interaction between central and peripheral chemoreflexes was non-significant in all subjects. PMID- 1626150 TI - Pathophysiology of inflammatory bowel disease. PMID- 1626151 TI - Overview of inflammatory bowel disease in humans. PMID- 1626152 TI - Feline lymphocytic-plasmacytic enterocolitis. PMID- 1626153 TI - Lymphocytic-plasmacytic enterocolitis in dogs. PMID- 1626154 TI - Canine eosinophilic gastroenterocolitis. PMID- 1626155 TI - Immunoproliferative enteropathy of basenjis. PMID- 1626156 TI - Endoscopic biopsy interpretation in canine or feline enterocolitis. PMID- 1626157 TI - [What is your diagnosis? Bilateral motor and sensory deficiency in the area of the musculocutaneus nerve]. PMID- 1626158 TI - [Colorectal carcinoma--current pathogenetic concepts. Significance of cell-matrix interaction for invasive growth and metastasis]. AB - Altered expression of certain cell-matrix receptors has been found to be specific for malignant, transformed epithelial cells in the large intestine. An attractive hypothesis, therefore, is that invasion and metastasis result from characteristic changes of these cell adhesion molecules. In animal models, it was possible to reduce the frequency of tumor invasion and metastasis and to achieve longer survival by modifications of cell membrane binding components on malignant cells. An increasing understanding of the role of receptor-mediated epithelium-matrix interactions in malignancy facilitates the development of new therapeutic concepts. PMID- 1626159 TI - [Adjuvant therapeutic possibilities in carcinoma of colon and rectum]. AB - Recently published results of large randomized trials have changed the recommendations for adjuvant treatment in patients with colorectal cancer. Patients with Dukes C cancer of the large bowel should be treated with a combination of Levamisole and 5-FU. For patients with rectal carcinoma Dukes B and C, a combined chemo-/radiotherapy is recommended. PMID- 1626160 TI - [Clinical aspects of acute diverticulitis and its complications]. AB - The diagnosis of acute diverticulitis is obvious if the patient presents with the typical symptoms of acute pain in the left lower abdominal quadrant and fever. A high index of suspicion, however, is required to diagnose diverticulitis with atypical presentation, which may be present in the elderly or immunocompromised patient. The detection of complications, most commonly diverticular abscess and colovesical fistulas, requires a careful and repeated examination and diagnostic skill. PMID- 1626161 TI - [Acute diverticulitis--radiological and endoscopic studies]. AB - In patients with suspected acute diverticulitis, plain abdominal radiographs may demonstrate free gas in the abdomen. Ultrasound can indicate the nature of disease but is not sufficient to assess the extent of the inflammation. If perforation is suspected, a water-soluble contrast agent should be used to demonstrate diverticulitis and peridiverticular abscess. Computed tomography is ideally suited for the evaluation of the disease. it permits the radiologist to tell the clinician the exact extent of the extramucosal inflammation and the involvement of adjacent organs and structures. PMID- 1626162 TI - [Current insights on the pathogenesis of chronic inflammatory bowel diseases]. AB - The pathogenesis and etiology of inflammatory bowel disease (IBD) is poorly understood. As a matter of fact, it is not even certain whether either one is a single entity with different forms of clinical manifestations, or whether each one represents a single clearly separable entity. Common features of both diseases are chronic persistence, recurrent exacerbation and remission, the production of autoantibodies, as well as the expression of aberrant HLA-class II molecules on the surface of epithelial cells on the site of inflammation gut. It is likely that these events involve a disturbed immunoregulatory function or autoimmune process. Since the beginning of investigation the cause of IBD, infectious agents (bacteria, virus, mycobacterium paratuberculosis and others) or bacterial products (endotoxin, peptidoglycans from the bacterial cell wall) have been considered as primary causes. Epidemiological studies showed a marked increase of the incidence rates of IBD in industrial countries leading to the hypothesis, that environmental factors could play a role in the pathogenesis of the disease. So far it is clear that the major identified risk factor for IBD is a genetic susceptibility confirmed by studies showing a positive family history. PMID- 1626163 TI - [Internistic therapy possibilities in therapy-resistant Crohn disease]. AB - About 20% of patients with active Crohn's disease do not respond to acute-phase therapy with glucocorticoids at an initial dose of 60 mg prednisolone-equivalent and stepwise dose reduction every week. In case of primary failure of this therapeutic scheme the dose of glucocorticoids has to be enhanced. If necessary a combination with total parenteral nutrition or tube feeding should be used. In case of early recurrence of inflammation during dose reduction or chronic steroid dependent disease activity a combination of glucocorticoids with Azathioprine will be successful in about 75% of patients. In addition a combination of glucocorticoids with tube feeding (elemental or polymeric diet) will lead to remission of inflammatory activity in about 60 to 70% of these patients. In patients, who are still refractory to these therapeutic procedures, operation should be discussed. PMID- 1626164 TI - [Cinitapride in the treatment of gastroesophageal reflux. Comparative study with metoclopramide and placebo]. PMID- 1626165 TI - [Clinical usefulness of the glucagon test in the study of pancreatic islet cell function]. AB - In an attempt to assess the utility of glucagon test as an index of beta cell function, we have studied the C-Peptide response to intravenous injection of 1 mg of glucagon in 77 patients with type I diabetes, 27 type II diabetics and 14 normal subjects. A significant difference between basal and glucagon-stimulated C Peptide levels as well as a good relationship between both values were observed in all groups (r values 0.91, 0.80 and 0.89 respectively). Both basal and stimulated C-Peptide concentrations showed significant relationship with the body mass index and total cholesterol levels, whereas both parameters were negatively related to insulin requirements in type I diabetic group. Absolute C-Peptide increment was different in all groups, despite it was not related to basal C Peptide levels. These findings confirm the usefulness of glucagon test as an investigative tool to assess the secretory capacity of beta-cell, suggesting that estimation of C-Peptide increment represents the best parameter to evaluate beta cell reserve. PMID- 1626166 TI - [Care of the terminally ill patient]. PMID- 1626167 TI - [73-year-old female with intermittent fever, splenomegaly and 15 kg weight loss]. PMID- 1626168 TI - [Comparative bioavailability and pharmacokinetics of Dolotren retard and Dolotren]. AB - A randomized crossover study was designed in order to evaluate the bioequivalence of a sustained-release preparation (DR) of diclofenac sodium (Dolotren RETARD) with respect to an enteric coated (D) tablet (Dolotren). For this purpose the bioavailability of both formulations, orally administered in single and multiple doses, was determined. Nine healthy volunteers were included in this study, receiving 100 mg of D and 100 mg of DR, firstly in single dose and then for 15 days b.i.d. for D group and once a day for DR group. For the analytical determination of diclofenac, blood samples at established time intervals, the day of the single dose and the 3rd, 7th and 15th day of multiple dose administration, were taken. The following kinetic parameters were determined: Cmac, tmax, alpha and beta, clearance, ka, area under the curve and absolute and relative bioavailability. When administered both endovenous and orally, the great interindividual variability in the kinetic characteristics of diclofenac sodium is evidenced. The lag time (tlag) for DR is 0.4 h, shorter than for D (2.2 h), which indicates a faster absorption in the upper sections of the gastrointestinal tract. Also tmax was shorter for Dr (1.9 h) than for D (4.3 h). Cmax obtained with D was higher tan with DR. The diclofenac sodium elimination process from plasma is significantly slower with DR than with D (t1/2 beta = 18.1 h and 2.5 h, respectively). In consequence, quantifiable plasmatic levels are maintained for at least 24 hours after administration of DR, but not of D. Absolute bioavailability of both preparations is about 80%, with great interindividual variations. Significant differences between the two preparations could not be demonstrated. Relative bioavailability between DR and D was 91.5%. None of the preparations when administered in repeated doses, D every 12 hours and DR every 24 hours, produced accumulation, neither their pharmacokinetic characteristics changed. Clinical and biological tolerance of both preparations were excellent, at doses used and for the period of time studied. Dolotren Retard is absorbed orally faster than Dolotren and maintains plasmatic levels longer, which allows it to be administered once a day, with a lesser incidence of undesirable effects related to Cmax. PMID- 1626169 TI - [Indications for operative hysteroscopy. A series of 418 interventions]. AB - Over a period of 38 months, from October 1, 1987 to December 31, 1990, 418 surgical hysteroscopies were carried out following systematic pre-operative hysteroscopy. Two-hundred and eighty-two patients presenting with a benign intercavitary lesion were treated by transcervical endo-uterine resection (EUR). The efficacy of the surgical method was assessed from the control of hemorrhagic phenomena, the most frequent sign. 89.7 percent of the patients who presented with menometrorrhagia, had become asymptomatic from the first cycle after EUR and 83.5 percent remained asymptomatic after a mean follow-up period of 28 months, 71 endometrectomies were carried out by EUR during this period, after careful hysteroscopic and histological evaluation of the endometrium. The results after one year of cycles were satisfactory in 82 percent of patients. Twenty-two patients presenting with a uterine septum were treated by endoscopic hysteroplasty. In most cases, the authors used the tip of the Charriere 21 resector. The follow-up period exceeds 1 year in 15 patients, 11 of whom became pregnant, giving birth to 9 live infants, 43 cases of synechia were treated by hysteroscopy in the context of Ashermann's syndrome. The functional results were good in 90 percent of patients, with the restoration of normal cycles. Only limited results were obtained in fertility in cases of muscular or fibrous synechia. The risks linked to surgical hysteroscopy are analysed. They appear to be acceptable, on condition that rigorous methods are used. The quality of sequelae and the short hospitalization make operative hysteroscopy preferable in the selected indications. PMID- 1626170 TI - [Conservative treatment of cancer of the ovary]. AB - The authors assess the potential of conservative treatment in a series of cases of ovarian cancer. Surgical evaluation is essential, in order to confirm that the conditions required for conservative treatment are present. The tumor must be a stage IA tumor, with a low histoprognostic score and small in size. Conservative treatment must be proposed in cases of tumors of potential malignancy and tumors of the sexual cords. It is debateable in epithelial tumors. The question of the necessity of further surgery to remove the genital tract after the desired pregnancies may be debateable in cases of epithelial tumors. PMID- 1626171 TI - [Hysteroscopic endometrial reduction. Analysis of 85 cases]. AB - The authors report the results of their experience of hysteroscopic endometrial reduction through a retrospective series of 85 patients who underwent surgery between October 1988 and February 1991. The indication consisted of hemorrhage (menorrhagia and metrorrhagia) of endometrial origin in women with a group mean age of 46 years who had no intention of becoming pregnant in the future. The pre treatment assessment was based on diagnostic hysteroscopy and was intended to eliminate neoplasm of the endometrium or its precursors. The endometrial reduction procedure always preserved an isthmic ring of endometrial tissue. No peroperative complication was reported. The mean duration of surgery was about 39 minutes. With a follow-up period of more than one year, bleeding had disappeared in 78% of cases. The authors conclude that the technic of endometrial resection in the treatment of benign lesions of the endometrium, on condition that the possibility of any disorder calling for laparotomy is ruled out and that there is regular postoperative follow-up. PMID- 1626172 TI - [Triplet pregnancies in France. Results of a retrospective, multicenter study of two years (1987-1988). Proposals for optimal management]. AB - The explosion of procedures for medically assisted parenthood (MAP) has resulted in a previously little known type of pregnancy: triple pregnancies. In order to assess the current obstetrical and pediatric situation, the authors have carried out a major retrospective, multicenter survey in France concerning the triple pregnancies from 1987 to 1988: 156 case histories have been collected. The finds are compared with those reported in the French and international literature, showing that in France, three-quarters of such pregnancies result from MAP, mainly due to ovulation-inducing agents. Hospitalization is prolonged (averaging 27 days), early (24 WA) and imposed by complications (in 8 out of 10 cases), prophylactic hospitalization being rarely prescribed. The main complications encountered are late miscarriages (1.9%), in-utero death (6.41%), dysgravidia (16.6%), hydramnios (5.12%) and serious cardio-pulmonary complications related to the use of beta-mimetics. A Cesarian is performed in only 87 percent of cases. The mean birth weight was 1,776 g. Neonatal mortality is on the decline, but still equivalent to 80.3 per thousand. Hypotrophy is common (27%). Birth is nearly always premature (99.3%), but very early prematurity (28-32 WA) was reduced. The approach suggested for optimum management is based on the personal experience of the authors, the findings of their survey and of the international literature. It is based on the prevention of prematurity and a fundamentally multidisciplinary approach. PMID- 1626173 TI - [Effects of preinduction by mifepristone on therapeutic abortions of the second and third trimesters induced by intravenous sulprostone]. AB - The authors investigate the effects of preinduction by administering 600 mg of mifepristone (RU486) per os before medical termination of pregnancy during the third to ninth months of pregnancy by intravenous sulprostone (Nalador). The study included a population of 35 patients treated with RU486 and then Nalador versus a population of 38 patients treated with Nalador only. The characteristics of the two groups did not show any statistically significant differences (medical, surgical and obstetric difference, indication for termination). The gestational age was lower in the RU486-Nalador group (group mean age : 20.9 weeks of amenorrhea versus 23.3, p less than 0.01). The group receiving RU486 significantly demonstrated the following : reduced time for induction of labour to modifications of the cervix (7.2 h versus 10.9 h, p less than 0.05), a higher number of rapid expulsions (within 10 h in 37.1% versus 15.7%, p less than 0.05) and a reduction of side effects (45.7% versus 71.05%, p less than 0.05). The other parameters analysed (duration of termination, total dose of prostaglandin) appeared to be better with RU486, but the values were not significantly different. PMID- 1626174 TI - [Neonatal consequences of premature rupture of membranes (more than five days) before the 34th week of gestation]. AB - Twenty-six cases of premature braking of the membranes which occurred before week 34 of amenorrhea and lasted for more than 5 days are assessed retrospectively. The mean age when the membranes broke was 26.6 weeks of amenorrhea. Delivery occurred on average at 31.5 +/- 2 WA, with an interval of between 6 and 91 days (mean 35 +/- 23 days). In 4 cases, chorioamniotitis complicated the premature breaking of the membranes. The perinatal mortality rate was 5 out of 27, including 2 still births. Nine of the neonates showed respiratory distress which required artificial ventilation. Four cases of pulmonary hypoplasia were confirmed by pathological examination. In all cases, this was associated with a reduction in the volume of the amniotic fluid, reduced fetal mobility and delayed intrauterine growth. In contrast, when these three factors were absent the prognosis was always good, regardless of the date at which the membranes broke. In the long term, the surviving children showed no neurological sequelae. PMID- 1626175 TI - [Umbilical Doppler velocimetry in prolonged pregnancies]. AB - One-hundred and eighty-seven single pregnancies, at full term determined accurately and confirmed by ultrasound before 17 weeks of amenorrhea and which were proceeding normally were monitored every 2 days after the expected end of term. This was done by conventional methods and in 132 cases by determining a placental resistance index (R = D/S). All the deliveries were carried out under monitoring and the infants examined by a pediatrician. The umbilical index at 280 to 300 days of gestation was found to be constant and equal to R = 0.52 +/- 0.041 (n +/- D) and the signs of fetal distress and post-maturity increased beyond term. In the first 80 pregnancies studies in this way, the determination of the value of the index R was not included in the decision-making process. Twelve of the 14 cases of fetal heart rate arrhythmia during delivery and all recorded cases of post-mature clinical signs and neonatal acidosis occurred when the index was above RI = 0.54. The next 107 pregnancies were randomly divided into two groups. In the 52 pregnancies in which the Doppler revealed an index at two consecutive determinations in excess of 0.54, this was taken to be a criterion for the induction of childbirth. In this group, some of the women gave birth earlier, without any increase in the number of Caesareans and this resulted in fewer post-mature infants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626176 TI - [Problems posed by the delivery of twin pregnancies]. AB - The authors present a retrospective study of 249 deliveries of twin pregnancies collected between 1987 and 1990. The incidence of twin pregnancies is 1.6%. Delivery is premature in 28.1% of cases and that of low birth weight is 51.7%. In 13.2% of cases, delivery was Cesarean and the Apgar score was significantly higher for the first twin than for second. Perinatal mortality was 7.2 percent. The authors compare these findings with those reported elsewhere in the literature. PMID- 1626177 TI - [Intra-fascial (or intra-cervical) hysterectomy with the help of a cervicotome. 33 cases]. AB - The authors report 33 hysterectomies carried out by abdominal route (isolated or combined with other surgical procedures) using a Cervicotome. This instrument carries out ablation of the endocervix and the junction zone without preliminary dissection of the paracervix. The operating procedure is explained: subtotal hysterectomy which is then completed using the Cervicotome. Hemostasis and closing of the section. The analysis of the outcome assesses preoperative complications and the quality of postoperative sequelae. The patient follow-up made it possible to analyse the anatomical and functional results (notably sexual). The advantages of this procedure over extra- and intra-fascicular hysterectomies are listed. This instrument was initially designed to eliminate the risks of lesions of surrounding organs during difficult hysterectomies (when dissection of the paracervix could be dangerous), but the operative convenience and quality of the outcome have led the authors to use it for all abdominal route hysterectomies. PMID- 1626178 TI - The utility of lipid-associated sialic acid (LASA or LSA) as a serum marker for malignancy. A review of the literature. AB - The utility of the lipid-associated sialic acid (LASA or LSA) test as a serum marker for malignancy is reviewed. The name LASA or LSA test is confusing because it suggests that only or mainly lipid-bound sialic acid is measured. In reality, glycoprotein-bound sialic acid is determined predominantly. The assay appears to have a particularly high positivity rate in leukemia, Hodgkin's disease, melanoma, sarcoma, advanced ovarian carcinoma and oropharyngeal tumors, suggesting that LASA may serve as a valuable marker in these malignancies. As a consequence of the rise of sialic acid-rich acute-phase proteins, such as alpha 1 acid glycoprotein, in inflammatory diseases the specificity of LASA and therefore its diagnostic accuracy is low. LASA can be useful for monitoring cancer patients during treatment, especially in combination with other tumor markers. PMID- 1626179 TI - Intracellular fluid of waybread (Plantago major) as a prophylactic for mammary cancer in mice. AB - The investigations were performed on female mice of the strain C3H Strong. Only the breeders were used in the experiments. A number of mice were given intracellular fluid of way-bread in subcutaneous injections. The controls received no treatment. The age at which mammary cancer appeared was noted and also how often the tumors occurred. The frequency of tumor formation was 93.3% in the controls and 18.2% in the treated mice. The difference is significant. PMID- 1626180 TI - Breast cancer mucin: an automated assay to detect mucus glycoproteins. AB - Episialin, a mucus glycoprotein, is a well-known tumor-associated antigen used in a variety of tests to detect the presence of adenocarcinoma. With the introduction of the microparticle-captured enzyme immunoassay (MEIA), a new technique was introduced. We compared this assay with our standard method to detect adenocarcinomas, the measurement of carcinoembryonic antigen (CEA). In breast cancer, the breast cancer mucin (BCM) assay was more often positive in metastatic disease but was not better than CEA in stages I-III. In lung carcinomas, BCM and CEA gave similar results while in colorectal carcinoma, CEA was superior. BCM gave similar results to CA 15.3 in a group of breast cancer patients. PMID- 1626181 TI - CA125 and placental alkaline phosphatase as serum tumor markers in epithelial ovarian carcinoma. AB - Placental alkaline phosphatase (PLAP) was measured by an immunoradiometric assay using the monoclonal antibody C2 (PLAP-C2). Serum samples of 135 patients with epithelial ovarian cancer were analyzed, and the results were compared with CA125 levels. CA125 and PLAP-C2 were elevated in 85 and 43% of the patients, respectively. Only 1 patient with normal CA125 and evidence of disease at the time of sampling had an elevated PLAP-C2. Fifty-three patients with measurable tumor were followed longitudinally during chemotherapy. Correct correlation with disease evolution was observed in 95% of the patients for CA125 and in 59% for PLAP-C2. The PLAP-C2 assay did not add significantly to the predictive value of CA125 in the diagnosis and follow-up of epithelial ovarian cancer. PMID- 1626182 TI - Serous ovarian cyst fluids contain high levels of endometrial placental protein 14. AB - This paper reports the detection and characterization of endometrial placental protein 14 (PP14) in human ovarian cyst fluids. PP14 from ovarian cyst fluid has the same molecular size as PP14 purified from human amniotic fluid. No clear difference was found in the PP14 concentrations between benign, borderline and malignant cyst fluids, but serous ovarian cyst fluids had significantly higher PP14 concentrations (median 253.3 micrograms/l) than mucinous cyst fluids (median 17.5 micrograms/l). PMID- 1626183 TI - cDNA cloning of new protein tyrosine phosphatases in the human colon. AB - Oligonucleotide probes corresponding to three invariant amino acid sequence motifs within the protein tyrosine phosphatase (PTPase) catalytic domain were synthesized and employed in the polymerase chain reaction (PCR). PCR products amplified from human colonic tissues were analyzed. Among 41 cDNA clones sequenced, two putative novel PTPases designated as CL-6 and CL-2B were isolated. cDNA cloning of CL-6 was performed, and three overlapped cDNA clones encoding part of the coding region, which was 2.1 kb long, were obtained. Expression of mRNAs of these clones was then investigated by Northern blot analysis or reverse transcriptase-PCR, suggesting that CL-6 mRNA may be expressed in a cell-type specific manner, whereas the expression of CL-2B mRNA could be ubiquitous. PMID- 1626184 TI - [Allografts of cryo-preserved and radio-sterilized spongy bone tissue. Their use in orthognathic surgery]. AB - In some circumstances, the orthognathic surgery creates inter-fragmentary spaces which have to be filled to ensure that the osteotomized segments are wedged and consolidated, and to avoid the appearance of unsightly subcutaneous contours. The authors report the results obtained through the use of cryo-preserved radio sterilized cancellous bone allografts, coming from femoral heads, used as fillers, in diverse types of osteotomy. Thus, 19 centers of osteotomy have been filled. Follow-up periods ranged from 5 to 20 months. In 8 cases, evidence was made through radiology of the blending of the grafts. The stability of the correction was constantly noticed as well as the perfectly harmonious facial contours, which testifies the osteogenic qualities of this material. No sepsis was observed. It is a quantitatively available material, of easy shaping, the use of which does not lead to a lengthening of the operation, nor to the creation of cutaneous scars. The risk of viral transmission through allografts, specially H.I.V. and hepatitis non A - non B - non C virus is nil due to the radiosterilization. PMID- 1626186 TI - [Stafne's cyst simulating a periapical cyst. Apropos 2 cases]. AB - We report about two cases of accidental radiological discovery of a radiolucent area that seemed to be related to the apex of the teeth. The diagnosis of a cyst is contested by performing a sialographic study of the submaxillary salivary gland, which demonstrates a benign abnormality known as Stafne's lacuna. PMID- 1626185 TI - [The first- and second-arch syndrome. A treatment analysis and plan]. AB - There is a very great lesion staging in these syndromes, and a great number of procedures have been described, according to the age and severity of the lesions. The initial assessment is therefore important, since it allows classifying these malformations according to their severity in key sectors. Scheduling the treatment in time must take account of: growth, the necessity to perform successive operations in one region, since no operation must hinder a subsequent one. It is essential to determine the optimum time for bone reconstruction. An early treatment with a conventional bone graft, without any intrinsic growth potential, condemns the reconstructed region to immobility, therefore to a progressive degradation of the result in time and to successive corrections. Early reconstruction is justified only if the available reconstruction means allow the reconstructed area to grow, either naturally or with the aid of orthopaedic stimulation. Some means seem to be available to date. A choice must therefore be made between: delayed morphological surgery, early functional surgery. Considering the extent of the means implemented, this is reserved for severe cases. The other great problem is the reconstruction of the auricle, which most often requires a series of operations scheduled over 2 years. The middle ear may not be operated if the lesions are unilateral. The other malformations, including macrostomia, muscular and neural abnormalities, involvement of the eyelids, sometimes require correction, which must fit in a repair schedule that must be established as soon as possible and must take account of the predictable procedures in order to prevent them from hindering each other. PMID- 1626187 TI - [The incidence of Actinomyces israeli colonization in tonsillar tissue. A histopathological study]. AB - The presence of the Actinomyces usually is not determined by the common histologic examination of preparations of tonsillar tissue which has been removed surgically. The Actinomyces are common saprophytic microorganisms which are found inter alia in the oral cavity and palatine tonsils. In this study, the authors examined histologically 238 surgical preparations of tonsillar tissue. In 84 of these, that is 35.21%, it has been noted, except the others, the presence of Actinomyces israeli. At the same time, the authors state their views concerning the contribution of the Actinomyces of tonsillar crypts to the pathogenesis of chronic tonsillitis. PMID- 1626188 TI - [The advantages and limits of the use of desmopressin (Minirin) in stomatology. Apropos 2 young female patients presenting with von Willebrand's disease]. AB - The authors describe two cases of wisdom tooth germ removal in female adolescents presenting with von Willebrand's disease. The effect of the Minirin injection was studied during a preoperative test and allowed carrying out the operation with normalized hemostasis, without using substitution factors and with no postoperative complications. The authors specify the indications and limitations of the use of desmopressin before surgery. PMID- 1626189 TI - [Respiratory pathology of sleep and the upper airways]. AB - Respiratory disorders in the upper respiratory tract during sleep are most often part of a continuous pathological process of long standing. Schematically, three clinical syndromes with increasing severity are described: breathing with the mouth open, snoring and the sleep apnea syndrome. These conditions always include a functional maxillofacial perturbation, which may be associated to a constitutional or acquired morphological disorder. Besides the medical approach itself, the treatment sometimes is surgical, always orthopedic. The earlier it is initiated, the more effective, simple and unconstraining it is. PMID- 1626190 TI - [Fractures of the condylar region]. AB - Condylar fracture are responsible for: homolateral TMJ disorders following discal apparatus lesions such as: disc displacement, discal lesion, osteoarthrosis of articular surfaces (condylar and temporal), contralateral TMJ disorders, more frequent, with destabilisation of the masticatory apparatus and decrease of ramus height or compensatory hypermobility. Functional treatment can prevent articular and muscular ankylosis. It is often indicated: non-displaced low undercondylar fractures or after surgery. Surgical reduction is indicated in two cases: displaced-low undercondylar fracture. The discal apparatus is intact and function usually excellent, displaced-high undercondylar fractures with 90 degrees head luxation. The bone reduction and contention must be associated to discal apparatus control. If dislocated or displaced, the apparatus should be replaced and sutured. Four factors are implicated in articular function: the fracture position, bone displacement (condylar head in or out of the glenoid fossa), discal apparatus integrity (the lower layer of the retrodiscal tissue is involved in bone regeneration especially in infants), and the quality of occlusion. PMID- 1626191 TI - [A comparative study of 2 series of mandibular osteosynthesis using screwed plates]. AB - In a retrospective study, we compared monocortical internal fixation versus bicortical screwing in the treatment of the mandibular fractures. Between 1983 and 1985, 40 patients underwent bicortical screw plate osteosynthesis and 46 were treated with the monocortical screw plate technique. The results are favorable to bicortical screwing, as regards both infection and pseudarthrosis. Monocortical screwing caused fewer occlusal disorders than bicortical screwing. Best on the increased amount of complications we decided to abandon the using of monocortical in favour with bicortical plates. PMID- 1626192 TI - [The sequelae of fractures of the orbital floor. An evaluation of the physical damage]. AB - The authors describe their experience with a homogeneous series of 88 fractures of the floor of the orbit. After a clinicopathological and therapeutic summary, the authors describe the sequellae encountered in their series. Sensory disorders are the most frequent sequellae, being noted in 30% of all cases. The maxillofacial surgeon and the ophthalmologist must cooperate to accurately evaluate the physical injury. The various items of damage are analyzed and evaluated. PMID- 1626193 TI - [A malignant salivary lymphoepithelial lesion with a poorly differentiated epidermoid carcinoma. Apropos a case]. AB - A case of malignant lymphoepithelial lesion of the submandibular gland is reported in a 71-years-old woman. The carcinoma showed a poorly differentiated pattern and its epidermoid nature was obvious after immunohistochemistry and electron microscopy. The epithelial nests were lying in an abundant lymphoid stroma consisting of small lymphocytes. A recurrence occurred ten months after surgical treatment. This observation is compared with those already related in the literature. PMID- 1626194 TI - [Osteosarcomas of the mandible]. AB - On the base of 3 cases of mandibular osteosarcoma, the current role of surgery is specified. The most often used procedure is Rosen's protocol, which includes: preoperative chemotherapy, radical surgery with reconstruction, and postoperative chemotherapy. The key element is the pathological study of the surgical specimen. This will determine the response of the tumor to preoperative chemotherapy and, by comparing the histology of the initial biopsy specimen to that of the surgical specimen, will be used as a basis to select the postoperative chemotherapy. For this type of tumor, chemotherapy has completely substituted for radiation therapy, which is no longer used in the initial treatment. Prophylactic lung radiation therapy has also been given up due to the risks of pulmonary fibrosis entailed by the effective doses. Surgery still has a role of choice in the therapeutic schedule, even if it cannot be contemplated as the sole treatment. Considering the usually young age of the patients, we currently think that reconstruction must be immediate and must resort to all the techniques likely to produce the best possible functional and morphological result. PMID- 1626195 TI - [The technic and advantages of using the tongue flap in the reconstructive surgery of cancer of the oral cavity. Our experience apropos 16 cases]. AB - In this study, primary we present briefly the main anatomic elements that concern the tongue as also the clinical and other structures of the cancer of the oral cavity. Simultaneously, we notice our experience from the use of the tongue flap in 16 patients with cancer of the floor of the oral cavity. This procedure is simple, easy, brief and it does not cause aesthetic problems to patients. It is also emphasized that this method does not create functional disabilities to the rest part of the tongue, with result the patients not have disturbances in speech, in chewing or in swallowing. PMID- 1626196 TI - [Mandibular reconstruction by a free peroneal transfer]. AB - After an anatomical study of the osteo-septo-cutaneous fibular flap, we reported 4 reconstructions of segmental mandible defects by this procedure, published in 1989 by D. Hidalgo. 2 patients presented mandibular defects associated with intraoral soft- tissue loss, following resection for epidermoid carcinoma with pre or post-operative radiation. The third patient had a multirecurrent ameloblastoma associated with extraoral soft-tissue extension. The fourth patient presented a complex loss of soft tissue and mandible following a war injury. The flaps survived in all patients. The osteo-septo-cutaneous fibular flap for mandible reconstruction has presented several advantages. The flap has been elevated under a tourniquet, the distant donor site has allowed a two-team approach. The osteo-septo-cutaneous blood supply has been adequate to support a skin island for intra or extraoral soft-tissue replacement. Biomechanical properties of the fibula have allowed fixation with miniplates and no postoperative intermaxillary fixation. Osteointegrated implants (Branemark) for dental rehabilitation were done for one patient. There was no long-term donor site morbidity. PMID- 1626198 TI - Non-Hodgkin lymphoma of the female urethra. AB - The third case of a malignant non-Hodgkin lymphoma of the female urethra is reported. The urethra was the primary localisation of the malignancy. In the two other cases which could be found in a literature review urethral involvement by this disease was secondary to other organs. In all cases the tumor first was described as a caruncle. Non-Hodgkin lymphoma should be considered in the differential diagnosis of urethral tumors. PMID- 1626197 TI - "Triple incision plasty". A convenient procedure for preputial relief. AB - Circumcision is the accepted operation to treat phimosis. However, when the purpose is to achieve retractility of a narrow foreskin to avoid further scarring and phimotic development after recurrent balanitis, a preputial plasty might be sufficient. Several methods with single or multiple incisions have been introduced throughout the years. None of them seems to have gained general acceptance. Single plasties tend to give cosmetically unsatisfactory results with an apparent cleft or deformity, while the multiple ones, where the deformity is more or less spread around the circumference, are not always easily done, at least not in children. Still, circumcision seems to remain the standard procedure for preputial relief. A simple technique, where three longitudinal incisions are transversely sutured, is described. It has been used in a series of 63 consecutive patients with good results, and seems to offer a good compromise between simplicity and cosmetical demands. PMID- 1626199 TI - The treatment of female bladder neck dysfunction. AB - During the period 1981-88, 38 women who eventually had the diagnosis of bladder neck obstruction established, were treated by bladder neck incision. Their age range was 28-85 years. The preoperative investigations included a full urodynamic examination and urethro-cystoscopy. The gynecologic examination was normal. The most constant finding was an elevated, rigid bladder neck seen by endoscopy. The treatment included a bladder neck incision either at 4 or at 8 o'clock. The results four weeks postoperatively were good, the symptoms had disappeared or the patients were improved in most cases, and the flow curves were normalized. Mean observation time was 55 months. After a longer period of time the symptoms in some cases returned, and then the incision was repeated. After the final control, we found 76% of the patients symptomatically improved. PMID- 1626200 TI - The expression of estramustine-binding protein in the human prostatic cancer cell line DU 145 is not androgen dependent. AB - Estramustine-binding protein (EMBP) constitutes one of the major proteins in the prostatic gland, it binds estramustine and estromustine, the active metabolites of estramustine phosphate (Estracyt). Previous studies in rats have indicated that the expression of EMBP is androgen dependent, with diminishing quantities following castration and estrogen treatment as well as restored pre-castration production upon administration of androgens. In this study, we have used the human prostatic cancer cell line DU 145 transplanted in female and male nude mice. This cell line, which is sex hormone independent, gave rise to subcutaneous tumors in the rats with no difference in growth characteristics between the males and females. The expression of EMBP was analysed by radioimmunoassay, immunohistochemical and Western blot techniques. No difference was seen between the two sexes with respect to EMBP content, demonstrating that the expression of EMBP, in contrast to that reported for the normal prostate, is neither androgen- nor estrogen-dependent in tumor tissues. PMID- 1626201 TI - Sexual function in men after radical cystectomy with or without urethrectomy. AB - Sexual function was evaluated in 21 patients with bladder carcinoma who had undergone radical cystectomy either with (n = 9) or without (n = 12) excision of the urethra. All patients received preoperative radiotherapy, and the cystectomy was done by a nerve-sparing surgical technique. At follow-up all patients reported normal sexual desire and tactile sexual activity. Eight of the 12 patients in whom the urethra was preserved could achieve penile erection and orgasm to tactile stimulation, and five of them had sufficient strength and duration of erection for sexual intercourse. Two of the nine patients in whom the urethra was removed-had weak erections insufficient for intercourse; three could experience orgasm. These results show that when cystectomy is done by a nerve sparing technique and without urethrectomy there is more chance of preserving sexual function than when simultaneous urethrectomy is done. PMID- 1626202 TI - Patterns of primary care and survival in 336 consecutive unselected Norwegian patients with bladder cancer. AB - The outcome of 336 unselected patients diagnosed as having bladder cancer in 1985 in a southern health region of Norway was studied. Two hundred and forty patients had superficial bladder cancer (Tis, Ta and T1). Seventy-four had T2-3 and 17 had T4 bladder tumours at the time of diagnosis (the T-category was unknown in five cases). In 46 of 248 evaluable cases (19%) 12 or more months had elapsed between the onset of symptoms and the histological confirmation of the diagnosis. The information received from the initial routine histology report was inadequate in 51 of 240 (21%) of the patients with superficial bladder cancer. Among the 91 patients with muscle-infiltrating tumours the primary treatment varied considerably, and only 15 patients underwent total cystectomy as the initial treatment. Only 46 in whom muscle-infiltrating tumours were diagnosed initially were referred to the regional uro-oncological unit during the course of the disease. The cancer-corrected, four-year survival was 86% and 42% for superficial and muscle infiltrating bladder cancer, respectively. The comparable figures for crude survival were 64% and 34%, respectively. The lack of optimal standard treatment of muscle-infiltrating bladder cancer warrants the introduction of clinical trials to assess both curative and palliative regimens as well as to study prognostic factors such as proliferation and immunohistochemical parameters by uro-oncological units. Scandinavian Cancer Registries should consider the optional recording of the T category on the case record forms for newly diagnosed cases of bladder cancer. PMID- 1626203 TI - Psychosocial adjustment and general state of health in patients with ileal conduit urinary diversion. AB - The psychosocial adjustment and general state of health were investigated in 66 patients (40 males, 26 females) who had been subjected to an ileal conduit urinary diversion on account of bladder cancer (44 patients) or incontinence or bladder dysfunction (22 patients). Seventy per cent of the patients reported unchanged, overall, social activity (OSA) after the operation. Twenty per cent reported less and 10% more activity. Bladder-cancer patients were more likely to curtail their social activities compared with the patients with incontinence or bladder dysfunction. Appliance-related problems were mentioned by half of the patients who reported decreased OSA. One-third of the patients considered accidental leakage or fear of such leakage as the most negative aspect of surgery. Factors related to an altered body image were the most common negative aspect reported by females. Despite psychosocial problems, the majority of the patients (80%) considered their health to be good. Males, individuals working full-time and patients with unchanged OSA scored higher on a Health Index, i.e. considered themselves healthier than the rest of the patients. PMID- 1626204 TI - Living donor nephrectomy. Complication rates in 490 consecutive cases. AB - 490 living donor nephrectomies were performed during a 25-year period, all through a retroperitoneal approach. In this report, short-term complications and donor renal function are analysed. There was no mortality. The major complication rate was 1.4%. There were 5 cases of postoperative haemorrhage requiring reoperation, one of which developed non-A-non-B hepatitis. There was one case each of septicemia and pulmonary embolism. All these patients recovered. Minor complications were noted in 13.6% of the cases, mostly bacteriuria or minor pulmonary infiltrates. There were 5 cases of reversible heart disorders and 6 cases of mental disorders. After 6-12 months, all donors had satisfactory function of the remaining kidney, which had increased its GFR by 32-38%. We conclude that the short-term consequences of donor nephrectomy are acceptable. From previous reports, from this unit and from others, it is evident that the procedure does not carry any definite long-term health risks. With a permanent shortage of cadaveric organs and with continued superiority in the outcome of living donor transplantations, this important resource should not be disregarded. PMID- 1626205 TI - Radiological examinations of the urinary tract. Changes during the last 24 years. AB - Procedures for imaging the urinary tract have been recorded in six Norwegian hospitals for the last 24 years. For three of the hospitals, data were collected from 1965 to 1989, and for the other three from 1966, 1971 and 1975, respectively. There was a significant reduction in the number of intravenous pyelograms, voiding cystograms, and renal angiograms, but the number of retrograde pyelograms and plain radiographs of the urinary tract remained constant. Computed tomography of the urinary tract increased during the first years, but after the introduction of ultrasonography, the number of computed tomograms decreased. Ultrasonographic examinations of the urinary tract are still rapidly increasing, and seem to have replaced some of the other imaging techniques. The present results should be taken into consideration when planning the health care for the future. PMID- 1626206 TI - Renal parenchymal function evaluated by scintillation camera renography before and after pyeloplasty for hydronephrosis. AB - Scintillation camera renography with Tc-DTPA was performed before and after pyeloplasty on 16 kidneys with urographic signs of pelviureteric obstruction causing hydronephrosis. Regional parenchymal renograms were generated, and the passage of Tc-DTPA through the parenchyma was measured and correlated to the change in separate glomerular filtration rate. Preoperative parenchymal passage of DTPA was significantly slower (p = 0.02) in kidneys with improved glomerular filtration rate after pyeloplasty than in those without such improvement. Postoperative passage of DTPA in parenchyma was almost identical with that in a reference series. This method seems to be clinically useful for evaluating cases of hydronephrosis and for predicting the outcome of pyeloplasty. PMID- 1626207 TI - Prophylactic antibiotics in the insertion of Tenckhoff catheters. AB - We assessed the efficacy of preoperative antibiotic prophylaxis in a prospective trial for patients undergoing insertion of Tenckhoff catheters for continuous ambulatory peritoneal dialysis (CAPD). The prophylactic regimen was a single dose of cefazolin (500 mg) and gentamicin (80 mg) given intravenously half an hour before surgery. There was no significant difference in the number of exit site infections (8 in the antibiotic group vs. 8 in the controls) and the number of episodes of peritonitis (5 in the antibiotic group vs. 2 in the controls). Our study showed that prophylactic preoperative antibiotics did not reduce the number of exit site infections and peritonitis after the insertion of Tenckhoff catheters. PMID- 1626208 TI - Effect of erythropoietin on sexual potency in chronic haemodialysis patients. A preliminary study. AB - Six male dialysis patients were submitted to a Doppler study of the deep penile arteries and intracavernosal injection of 30 mg papaverine under basal conditions before and after erythropoietin therapy. Penile tumescence was recorded after 15 min by measuring the length and the circumference of the penis as well as the erectile angle between the penis and the legs with the patient in standing position. Haematocrit was raised by erythropoietin therapy from 19.3 +/- 4.5 to 31.2 +/- 5.5 within 3 months. Five patients completed the study. We encountered a significant improvement in the frequency of sexual intercourse per month from 1.3 +/- 0.5 to 2.3 +/- 0.8 (p = 0.014). Furthermore, an increase was observed in the penile brachial index (from 0.87 +/- 0.1 to 0.91 +/- 0.1) and in the papaverin induced increase in penile length (4.6 +/- 1.4 cm versus 5.2 +/- 1.1 cm), penile circumference (2.7 +/- 0.14 cm versus 2.7 +/- 0.27 cm) as well as in the erectile angle (61.7 +/- 37.1 versus 80 +/- 23.5 degrees). These changes were not statistically significant. There was a significant correlation between the increase in the erectile angle and the increase in frequency of intercourse (p = 0.04). In conclusion, erythropoietin treatment could improve the sexual potency in uraemic patients under chronic haemodialysis therapy. PMID- 1626209 TI - Leiomyoma of the bladder. Case report. AB - A 33-year-old woman was incidentally noted to have a benign bladder leiomyoma on pelvic ultrasonography during pregnancy. This was resected and she made an uneventful recovery. Leiomyomas of the bladder are rare and usually asymptomatic; the treatment is excision. PMID- 1626210 TI - Successful pregnancy after ileocystoplasty. Case report. AB - A 32-year-old woman with multiple sclerosis had an uncomplicated pregnancy and labour two years after successful "clam" ileocystoplasty for urge incontinence and frequency of micturition. She remained well after three years following. PMID- 1626211 TI - Spontaneous bladder rupture after colocystoplasty. Case report. AB - An 18-year-old girl had bladder extrophy managed by sigmoid cystoplasty with clean intermittent catheterization. Spontaneous bladder rupture occurred 12 months after reconstructive surgery. The diagnosis was made by ultrasound with abdominal tapping and cystography under fluoroscopy. Management included intravenous antibiotics, laparotomy and closure of the perforation. The diagnosis was delayed and postoperative intraperitoneal abscess formation occurred. PMID- 1626212 TI - Fatal outcome of bilateral nephrectomy in a patient with polycystic kidney disease. Case report. AB - A 49-year-old woman had polycystic kidneys and liver cysts first diagnosed in 1968. She presented with hepatic and renal failure in 1980 and by 1988 was undergoing regular haemodialysis. In February 1989 she had bilateral nephrectomy (before renal transplantation) but developed septic shock and died. The reported mortality of bilateral nephrectomy before kidney transplantation is about 5%, and patients should be carefully selected and assessed before operation. PMID- 1626213 TI - Primary malignant melanoma of the urinary bladder. Case report. PMID- 1626214 TI - Light chain nephropathy. Case report. AB - Two patients with light chain nephropathy are described. The diagnosis and management of this rare condition is discussed. PMID- 1626215 TI - Treatment of primary chronic glomerulonephritis with immunosuppressive and anti inflammatory agents. Review. PMID- 1626216 TI - Seventh report on the standardisation of terminology of lower urinary tract function: lower urinary tract rehabilitation techniques. International Continence Society Committee on Standardisation of Terminology. PMID- 1626217 TI - Foreign body reaction after modified silicone rubber arthroplasty of the first carpometacarpal joint. AB - Twenty patients who had been treated with a silicone rubber trapezial implant for degenerative changes in the first carpometacarpal joint were evaluated radiologically and clinically. After a mean follow up of 4.5 years, 11 of the 20 required reoperation and removal of the prosthesis for persisting pain and weakness. In all hands in which the prosthesis remained radiographs showed bone resorption or carpal bone cysts typical of silicone particle synovitis. In the light of these results we now do not recommend this procedure for the treatment of arthritis of the first carpometacarpal joint. PMID- 1626219 TI - Multiple symmetric lipomatosis: combined surgical treatment and liposuction. Case report. AB - A 47 year old man with a history of alcoholism presented with symmetrical lipomas on the shoulders, neck, and chest. He also had lipomatous areas on the trunk and thighs. He was treated with a combination of surgery and liposuction, and made an uneventful recovery. Histological examination confirmed the diagnosis of multiple symmetric lipomatosis, a rare disorder only about 200 cases of which have been reported. The aetiology is unknown, but is often seen in patients with a history of alcoholism. PMID- 1626218 TI - Transfer of the second toe for reconstruction of the hand after trauma. AB - Twenty-six transfers of second toe to hand have been carried out in 25 cases. On 25 occasions the toe was anastomosed to the stump of the thumb, and in one to a metacarpal hand. Revascularization failed in five cases, but the remaining 21 healed with bony union occurring within six weeks in all cases. The mean follow up period was 52 months, range 14-81, and the results in 19 thumb cases were classified as excellent and in one as good by the Tamai score. We conclude that the microsurgical technique of transferring the second toe to the hand is challenging, but if revascularization is successful the functional results are good. Morbidity at the donor site is minimal. PMID- 1626221 TI - Calcifying aponeurotic fibroma. A case of multiple primary tumours. Case report. AB - A 20 year old man had had three subcutaneous tumours on his left forefinger for 15 years. After operation they were found to be infiltrating into the surrounding tissue, and histological examination showed them to be calcifying aponeurotic fibromas. To the knowledge of the author this is the first reported case of multiple primary tumours of this kind. PMID- 1626220 TI - Traumatic false aneurysm of finger tip. Case report. AB - A 13 year old girl presented with a false aneurysm of the tip of the left middle finger. This was treated by ligation of the branch of the digital artery and sac excision. The patient made an uneventful recovery. To our knowledge, only 10 such cases have been reported, and these were all proximal to the distal interphalangeal joint. PMID- 1626222 TI - Prepared neurovascular forehead island flap for reconstruction of minor full thickness nasal defects. Case report. AB - A forehead neurovascular island flap has twice been used for reconstruction of minor full thickness nasal defects caused by surgical removal of malignant tumours. The flap was raised one month before transposition, and a split thickness skin graft was applied to the inner surface of the galea of the flap. The periosteum of the forehead was also grafted, thus repairing the donor site before the flap was removed. The flap is based on the supraorbital artery, which was dissected to its origin at the incisura or supraorbital foramen. The advantages are those of a small flap with external as well as internal lining and with preserved sensibility. PMID- 1626223 TI - Diagnosis of induced cleft palate in rats from defective patterns of differentiation of isoenzymes. AB - Cleft palate was induced in 420 embryos of Sprague-Dawley rats with a single oral dose of 600 mg/kg beta-aminoproprionitrile (BAPN) on embryonal day 15, 7 hours. The cleft palate was accompanied by a pathological differentiation pattern of various isoenzymes in palatal shelves. These isoenzymes could be detected in amniotic fluid from the 16th to the 20th days of pregnancy when they also had a pathological differentiation pattern. We conclude that teratogenically induced cleft palate in rats is accompanied by a pathological differentiation pattern that can be traced by determination of isoenzymes in the palatal shelves as well as in amniotic fluid. PMID- 1626224 TI - Ischemia in wound healing. I: Design of a flap model--changes in blood flow. AB - A standardized ischemic, H-shaped, double flap model in rats was developed for investigating the influence of different factors that could potentially increase flap survival. The blood flow was measured in the flaps as well as in normal healing incisional wounds on day -1 (intact skin) and on days 1, 4, 8, and 16 by the xenon-133 (133Xe) clearance technique. The flow in normal healing incisional wounds remained the same as the flow in intact skin. The flow in the flaps, however, initially decreased to ischemic levels, but afterwards gradually increased to that of normal healing incisional wounds and intact skin. Further, the cutaneous blood flow in both the cranially and the caudally based ischemic dorsal flap was independent of the width of the flap. PMID- 1626225 TI - Temperature load test to increase the accuracy of laser Doppler monitoring of flaps. AB - A heat and cold provocation test was evaluated in 10 porcine island flaps to improve the quality of monitoring flap circulation by the laser Doppler technique. When the pedicle blood flow was undisturbed there were significant increases in flow after a heat stimulus (p = 0.01), whereas no significant flow changes were noted during arterial or venous occlusion. This method can increase the accuracy of the laser Doppler technique in monitoring the circulation in skin flaps. PMID- 1626226 TI - Laser technology in plastic surgery. PMID- 1626227 TI - The effect of preoperative needle abrasion of the recipient site on survival of autologous free fat grafts in rats. AB - Pads of fat ranging from 670-1758 mg in weight were taken from the right groins of 20 rats and implanted subcutaneously over their right pectoral muscles. One week previously the recipient site on the thorax had been abraded with a needle in 10 of the rats. After three months the transplanted fat was taken out, weighed, and examined histologically by light microscopy. Regional tissue blood flow in the transplanted fat and in the fat from the left groin was measured by the microsphere technique. The amount of surviving fat and blood flow in the fat transplanted to an abraded recipient site was significantly higher than in the control group after three months. We conclude that preoperative needle abrasion of the recipient site may increase the chance of revascularisation and survival of the transplanted fat in rats. PMID- 1626228 TI - Conditioning effect induced by chronic nerve compression. An experimental study of the sciatic and tibial nerves of rats. AB - To find out if chronic nerve compression could affect the peripheral nerve by acting as a "conditioning lesion", silicone tubes (internal diameter 0.8-1.6 mm) were placed round the sciatic or tibial nerves of adult rats for different time periods. After the period of compression the tubes were removed and a test crush lesion was made on the sciatic nerve in the thigh. Regeneration distances of the sensory nerve fibres were analysed by the pinch reflex test after a further three or six days. Compression of sciatic or tibial nerves induced a significant increase in outgrowth length compared with nerves subjected to mobilisation and crush lesion alone. All the tubes tested had a conditioning effect, but only tubes with a small internal diameter seemed to induce nerve fibre degeneration as assessed by immunocytochemistry. The results showed that chronic compression induced a regenerative response in the peripheral nerve. The mechanism by which this was accomplished remains obscure but it may involve both the neurons and the non-neuronal cells. PMID- 1626229 TI - Reconstruction of ligaments with expanded polytetrafluoroethylene. An experimental study in rabbits. AB - The medial collateral ligaments in the knee joints of 15 rabbits were replaced with expanded polytetrafluoroethylene (E-PTFE). The joints were not immobilised postoperatively, and their structure and function were evaluated after 12 months. Range of motion was equal in all groups. Stability of the knee joints and breaking strength of the ligaments were similar in the group in which the ligament had been reconstructed and in the sham operated control group (n = 8). The group in which the ligament had been severed and left to heal by formation of scar tissue (n = 7) had significantly reduced joint stability and the breaking strength of the medial collateral ligament was significantly less. The E-PTFE ligaments were well incorporated into the surrounding tissues. There were no adverse tissue reactions and the articular cartilage looked normal both macroscopically and microscopically. These results indicate that E-PTFE might be a useful substitute for damaged ligaments, at least in smaller joints like metacarpophalangeal and interphalangeal joints. PMID- 1626230 TI - Birth weight and placental weight in cleft probands. AB - The mean birth weight of the 1,568 probands with clefts who were born in Finland between 1975 and 1985 was 3,346 g, which is lower than the mean of all live born babies in 1980 (3,541 g). The 345 who had an associated anomaly or syndrome had a mean birth weight of 3,027 g and placental weight of 538 g, compared with 3,435 g and 609 g, respectively, for those with solitary clefts. The more severe the cleft the lower the birth weight, but not the placental weight. The percentage of low birthweight (less than or equal to 2,500 g) infants was higher than in the general population (8.5% compared with 3.8%). The highest percentage of low birthweight infants was in the subgroup with bilateral cleft lip and palate (16.8%). PMID- 1626231 TI - Craniofacial development in children with unilateral clefts of the lip, alveolus, and palate treated according to four different regimes. II. Mandibular and vertical development. AB - Lateral skull radiographs of 85 patients with unilateral clefts of the lip, alveolus and palate treated according to four different regimes were compared longitudinally, at three different ages, regarding mandibular and vertical facial development. It was found that there were no lasting differences in mandibular morphology resulting from regimes including primary or early secondary bone grafting. The non grafted group, however, showed increased mandibular length and anterior height. The jaw angle was increased and there was a more favourable sagittal jaw relationship. Regimes that included primary bone grafting were associated with reduced upper anterior facial height, which resulted in less harmonious facial proportions compared with treatment regimes including early secondary bone grafting done during the mixed dentition, or no bone grafting at all. Vertical development was greatest where bone grafting was excluded. PMID- 1626232 TI - The early gingivoalveoloplasty. Preliminary results. AB - To try and achieve good alveolar structure without the need for later bone grafting, we have carried out secondary gingivoalveoloplasties in 19 consecutive patients with cleft lip and palate at a mean age of 36 months (range 19-68). The lip and soft palate had been repaired at a mean age of 6 months. Preliminary results suggest that simultaneous closure of the hard palate and reconstruction of the alveolomaxillary cleft results in good formation of new bone and good or reasonable alveolar structure, so obviating the necessity for bone grafting at the age of 9-10 years. Long term follow up is needed to confirm these results. PMID- 1626233 TI - Correlation between the age at repair and speech outcome in patients with isolated cleft palate. AB - The effect of the age at primary palatal repair on the speech of 3-year old children with isolated cleft palate was assessed. The group comprised 108 consecutive children whose palates were repaired at the mean ages of 12.9 (n = 45), 18.5 (n = 18) and 22.1 months (n = 45). Signs of cleft palate speech and the degree of speech impairment were recorded. The signs sought were: hypernasality, audible nasal air emission, and misarticulations associated with velopharyngeal insufficiency. The speech impairments were subdivided into three categories by combining the signs of cleft palate speech. The results showed that children who were operated on at the age of about 12-18 months were significantly better speakers than those operated on later. Of these 46 were rated as normal or practically normal speakers (73%), compared with 10 of the children who had their repairs delayed until about 22 months (22%). As a result of the speech evaluations, it was predicted that 5 (11%), 0 and 21 (47%) children in the early, middle, and late closure groups, respectively, required secondary surgery to eliminate signs of cleft palate speech associated with velopharyngeal inadequacy. The numbers who had secondary surgery were 4, 0 and 18 in the three groups. PMID- 1626235 TI - Breast reconstruction using tissue expansion. AB - To assess the advantages of tissue expansion as a method of breast reconstruction, a prospective, consecutive study was carried out in 41 women who had undergone mastectomy. The expander was positioned in the submuscular plane and expanded weekly to double the volume of the calculated permanent implant. A permanent gel implant was inserted after 10 weeks. Two examiners judged the rate of capsular contracture after 15 and 32 months according to the Breast Augmentation Classification. The rate of capsular contracture was 28% at the second follow-up. Major complications were rare--7%. The patients were pleased with the overall result in 82% of cases. We conclude that tissue expansion is safe, produces a good result and causes few complications with only minor discomfort to the patient. PMID- 1626234 TI - The retroauricular coronal incision. AB - The coronal incision has been modified so that if it needs to be extended to improve exposure, the extension will be behind the ear and therefore less noticeable. The incision has been used in 25 adults and 30 children with no complications. Its cosmetic appearance is superior to the preauricular coronal incision, and it is preferred especially by young people in whom the scar tends to widen with time. PMID- 1626236 TI - Microvascular reconstruction of soft tissue and bone loss in war wounds. AB - Seventy-seven skin and bone defects caused by high velocity missiles have been repaired with various combinations of microvascular free transfer of skin flaps and vascularised bone grafts. We concluded that the free osteoseptocutaneous fibula transfer (1,4) is the best method of reconstruction if a long bone defect is associated with skin loss. PMID- 1626237 TI - Total wrist arthroplasty. Experience with Swanson flexible silicone implants, 1982-1988. AB - In a study of the results of silicone rubber arthroplasty of the wrist 18 patients (19 operated wrists) were re-examined after a mean follow up of five years. Experience with the ulnar head implant was discouraging, and it was not used in the last eight wrists. This did not affect the outcome, patients having good supination and pronation without pain. The range of motion with the radiocarpal prostheses was 0-70 degrees, mean 39 degrees. Radiological results showed severe subsidence in all patients followed up for more than two years, and prosthetic fracture in five (26%), which was disappointing. Nevertheless the patients had a useful range of motion and all but two were relieved of pain. By the patients' own assessments 16 wrists were considered good, one fair, and two poor. Predictors of failure (prosthetic fracture) were poor alignment before operation, postoperative range of motion of more than 50 degrees, and rupture of the carpal extensor tendon. With these reservations we recommend the silicone spacer as the best solution for most patients with severe problems of the wrist as a result of rheumatoid arthritis. PMID- 1626238 TI - Microbeam studies of the sensitivity of structures within living cells. AB - Determining the biological effects of low doses of radiation with high linear energy transfer (LET) is complicated by the stochastic nature of charged-particle interactions. Populations of cells exposed to very low radiation doses contain a few cells which have been hit by a charged particle, while the majority of the cells receive no radiation damage. At somewhat higher doses, a few cells receive two or more events. Because the effects of damage produced by separate events can interact in the cell, we have had to make assumptions about the nature of these interactions in order to interpret the results of the experiments. Many of those assumptions can be tested if we can be sure of the number of charged-particle events which occur in individual cells, and correlate this number with the biological effect. We have developed a special irradiation facility at Pacific Northwest Laboratory (PNL) to control the actual number of charged particle tracks that pass through cell nuclei. The beam from a 2 MeV tandem accelerator is collimated to approximately 5 microns. Cells, grown in special dishes with 1.5 microns thick plastic bottoms, are positioned so that the desired portion of the cell aligns with the collimator. A shutter in the beam line is opened and closed after the desired number of particle tracks has been counted. This approach can be used to investigate the effects of the interaction between irradiated and unirradiated cells in an organized system, as well as to study the effects of spatial and temporal distribution of radiation damage within single cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626239 TI - The effect of colcemid on the heat survival of mitotic V79 Chinese hamster cells. AB - V79 Chinese hamster cells were collected by colcemid addition to study the effect of heat on mitosis. When they were heated at 42 degrees C and 45 degrees C in the presence of 0.06 micrograms/mL colcemid, cell survival increased over the control samples, which were heated in ordinary medium. Scanning electron microscopy showed that cells heated to 45 degrees C in the presence or absence of colcemid had fewer microvilli on the surface, but they did not have increased bleb formation. Transmission electron microscopy showed that the chromatin was diffuse in the heated cells and the kinetochores were indistinct. The mitochondria in the heated cells were also swollen and contained visible particles. PMID- 1626240 TI - A light, transmission and scanning electron microscope study of snuff-treated hamster cheek pouch epithelium. AB - The effects of smokeless tobacco (snuff) on hamster cheek mucosa were studied by light microscopy, transmission (TEM) and scanning electron microscopy (SEM). Two grams of commercially available smokeless tobacco were placed into the blind end of the right cheek pouch of each experimental animal, once a day and five days a week for 24 months. The control animals did not receive smokeless tobacco. After 24 months treatment with smokeless tobacco, hamster cheek mucosal epithelium lost its translucency and had become whitish in color. By light microscopy hyperorthokeratosis, prominent granular cell layers with increased keratohyalin granules and hyperplasia were seen. At the ultrastructural level, wider intercellular spaces filled with microvilli, numerous shorter desmosomes, many thin tonofilament bundles, increased number of mitochondria, membrane coating granules and keratohyalin granules were seen in snuff-treated epithelium. The changes in the surface of the epithelium as seen by SEM were the development of an irregular arrangement of the microridges and the disappearance of the normal honeycomb pattern. The microridges were irregular, widened and surrounded the irregular elongated pits. Some smooth areas without microridges and pits were also seen. The long-term histological, TEM and SEM changes induced by smokeless tobacco treatment of the epithelium are well correlated with each other and were similar to those reported in human leukoplakia without dyskeratosis. They imply changes of pathological response resulting from topically applied snuff. PMID- 1626241 TI - Levels of complexity in the microstructure of mammalian enamel and their application in studies of systematics. AB - Description and analysis of the complex structure of enamel can be facilitated through the application of a system of hierarchical levels of structural complexity. Five interdependent levels are distinguished. These are the levels of: 1) crystallites, 2) prisms, 3) enamel types, 4) schmelzmuster, and 5) dentition. This system provides a basis for analysis of both variation of particular structures and variation of structural types throughout a mammal's dentition. Optimally, in wide ranging systematic and biomechanical studies, all levels of structural complexity should be considered, but lack of information about one level does not prevent significant analyses at other levels. PMID- 1626242 TI - Architecture of mixed calcium oxalate dihydrate and monohydrate stones. AB - Calcium oxalate dihydrate (COD) and monohydrate (COM) are the most frequent constituents of urinary stones, and there still exist some questions about the interrelation between the two hydrates. Architecture of mixed COD and COM stones was observed by electron microscopy to solve the questions. The fractured surface of a stone is composed of the fractured face of the crystals. In this situation a morphological criterion of typical dipyramid shape is useless to identify COD. But we could identify COD using the partial dissolution method, which etched square pits on COD crystals. COD and COM formed distinctly separate layers. COD was always found in the stone surface and COM in the center. The stone surface was covered by a thick layer of organic matrix, and the intercrystalline space was filled with matrix. The crystals were grown thrusting the matrix aside to minimize the space. Although COD is more soluble than COM, the urine contains specific substances that favor the formation of COD. Supposing the stone matrix excludes these substances selectively, the gel-state matrix provides a preferable condition for COM formation. This hypothesis is suitable to explain the high incidence of COM stones. An abrupt change of the crystalline constituent can be explained by COD crystal deposition on COM stones. Frequent COD crystalluria can explain why COD is always found in the stone surface. Once the stone surface is covered with COD crystals, they continue to grow in the gel-state matrix or deposit further to form the bulk of the stone. PMID- 1626244 TI - Idiopathic calcium oxalate nephrolithiasis: a cellular disease. AB - Physico-chemical, metabolic and hormonal theories regarding the pathogenesis of calcium oxalate nephrolithiasis do not sufficiently explain many features of this disease. The recent findings of an abnormally faster oxalate self-exchange and higher phosphorylation of band 3 in erythrocytes of idiopathic calcium oxalate stone formers suggest the hypothesis that nephrolithiasis may be a cellular disease, characterized by a defect in the function of the anion-exchange. The cellular anomaly seems genetically controlled. Band 3 anion exchanger function seems to be biochemically regulated through modulation of band 3 phosphorylation, which depends on cyclic AMP- and phospholipid-sensitive Ca2+ independent protein kinases. In this light, a reduced glycosaminoglycan concentration in the erythrocyte membranes of stone formers might play a role, as these molecules exert a strong inhibitory effects on band 3 phosphorylation and anion transport in vitro and in vivo. An in vivo trial was performed in which stone formers were administered glycosaminoglycans orally. A reduction in oxalate excretion, and oxalate renal clearance, and a simultaneous correction of the abnormal RBC oxalate flux and band 3 phosphorylation were observed. These data suggest the existence of a link between the erythrocyte abnormality and oxalate transport by the kidney and gut. PMID- 1626243 TI - Factors affecting fasting urinary calcium excretion in stone former patients on different dietary calcium intake. AB - The effects of variable calcium content on daily and fasting urinary calcium and other lithogenic solutes excretion, on the bone turnover index (fasting hydroxyproline urinary excretion) and on the calciotropic hormones were studied in 312 stone former patients with an outpatient protocol and 15 stone former patients in an inpatient study. Furthermore in 60 of these patients, 30 while on a low calcium diet (LCD) and 30 on a free calcium home diet (FCD), the effects of an oral calcium load (OCL) on bone turnover index, calciotropic hormones and calcium excretion were evaluated. The results demonstrate that an LCD is effective in reducing daily calcium excretion. Fasting calcium excretion is apparently not affected by changes in dietary calcium content. On the other hand, LCD induces a marked increase in bone resorption, without apparent signs of increased parathyroid activity. This may explain the failure to reduce fasting urinary calcium excretion by the LCD. The OCL greatly reduced bone resorption rate, without any change in calciotropic hormones, especially in patients on LCD. In conclusion, the LCD induces a reduction in the lithogenic factors in the urine of stone formers, but induces a marked increase in bone resorption. The lack of any change in fasting urinary calcium excretion in conditions of different dietary calcium intake may be due to an opposite change in the intestinal and osseous components that affect this parameter, and is therefore of little value. PMID- 1626245 TI - The microvasculature of human oral mucosa using vascular corrosion casts and India ink injection. I. Tongue papillae. AB - The microvasculature of human tongue papillae originating from 9 males and 6 females, aged 0.5 to 2 years was studied by scanning electron microscopy (SEM) of vascular corrosion casts and by light microscopy (LM) of India ink injected specimens. All papillae showed a microvasculature characterized by primary, secondary and tertiary capillary loops. In the filiform papillae the loops were generally arranged in a corolla-like pattern with the tertiary loops demonstrating a hair-pin shape. The fungiform papillae showed basically a similar architectural pattern although the loops were somewhat more compact and complex in structure. A small, shallow depression of the tertiary loops at the top of these papillae was found to be occupied by a prominent rete ridge of the surface epithelium. There was a gradual transition from filiform to foliate papillae, the latter appearing as rows of coalesced filiform papillae. The circumvallate papillae easily identified by the surrounding furrow showed a rather complex and compact pattern of capillary loops of which typical hair-pin shaped tertiary loops dominated the periphery of the papilla. Small grooves or depressions in the vascular network were found to be occupied by rete ridges of the overlying mucosal epithelium. PMID- 1626246 TI - Correlative transmission electron microscopy and high resolution scanning electron microscopy studies on the fine structural organization of the chicken pituitary gland. AB - The present study employs transmission (TEM) and high-resolution scanning electron microscopy (HR-SEM) to examine the inter- and intra-cellular organization of the pars distalis of the chicken anterior pituitary gland. The overall view of the cryofractured surface of the par distalis illustrates the arrangement of different pituitary cells and tissues in the follicles. Fine structural examination by HR-SEM shows that the membrane of the mitochondria has a similar configuration to that of the rough endoplasmic reticulum. Granule-like structures, on the surface of the mitochondrial membrane, are similar in size to ribosomes. Standard imaging and three-dimensional imaging demonstrated the formation of developing granules inside the Golgi sacs and the release of mature granules from the end of Golgi stacks. The occurrence of granule-granule connections suggests that granules may be released by exocytosis in groups or individually. PMID- 1626247 TI - Structural artifacts and advantages of cytocentrifugation of cells as viewed by scanning electron microscopy. AB - Cytocentrifugation of cell suspensions onto glass slides is a widely used procedure in contemporary cytology. We employed here scanning electron microscopy (SEM) to investigate putative morphological changes induced in cells submitted to cytocentrifugation. The fine structure of murine pleural exudate cells (macrophages mainly) processed by spinning was compared with that of similar cells treated without centrifugation (poly-L-lysine attachment of the cells to glass slides at 1 g). Cells of cytocentrifuged preparations showed a significant increase in diameter and smoothening of the cell surface as compared with the morphology of non-centrifuged cells. Cytocentrifugation also induced the formation of thin elongations coming out of the cellular outlines. The centrifugation-induced flattening of the pleural macrophages improved the detection of large intracellular inclusions (containing tungsten particles): these bodies were readily identified by secondary-electron imaging mode of SEM in cytospinned cells whereas their detection in non-centrifuged spherical cells required the use of the backscattered-electron imaging mode of SEM. We conclude that the cytocentrifugation methodology, on one hand, requires caution on the interpretation of the microanatomy of the cells and, on the other hand, the procedure may be an adequate method to improve the identification of large intracellular inclusions by routine (secondary-electron imaging mode) SEM. PMID- 1626248 TI - [Significance of bronchial alveolar lavage in the diagnosis of eosinophilic pneumonia]. AB - We describe 3 cases of eosinophilic pneumonia of unknown etiology with atypical clinical findings diagnosed by bronchoalveolar lavage (BAL). In 2 patients with subacute symptoms and restrictive ventilatory dysfunction there was no eosinophilia in peripheral blood, and chest X-ray showed a bilateral acinar and mixed interstitial-acinar pattern respectively. Transbronchial lung biopsies revealed only nonspecific changes. The third patient had acute respiratory failure and the eosinophils in peripheral blood were 1500/microliters. Chest X ray demonstrated only minimal interstitial changes. In all instances the eosinophilic pneumonia was diagnosed by a marked BAL-eosinophilia of 25 to 45%. No specific etiology could be detected for the eosinophilic lung disease. The response to treatment with corticosteroids was prompt. PMID- 1626249 TI - [Perioperative morbidity and mortality of colon resection in colonic carcinoma]. AB - An analysis of the local and systemic perioperative complications is conducted to explore the risk of resection of colon cancer. In a retrospective study we analyzed 231 consecutive patients operated on between 1984 and 1988. The mean age was 70 (37-91) years. The operations consisted in 3 ileocecal resections, 144 right hemicolectomies, 10 resections of the transverse colon, 22 left hemicolectomies, 77 resections of the sigmoid colon and 5 subtotal colonic resections. 2 patients (0.9%) had a clinical leakage of the anastomosis. 3 patients were reoperated: one because of anastomotic leakage and two because of ileus due to small bowel adhesions. 2 patients with uncomplicated local healing died within 30 days after the operation from systemic complications (mortality 0.9%). It is concluded that with standardized preoperative bowel preparation, prophylactic perioperative antibiotics and modern anesthesia, the resection of colon cancer is today possible with minimal perioperative risk. PMID- 1626250 TI - [Helicobacter pylori colonization of the gastric remnant following partial resection]. AB - Colonization by Helicobacter pylori (HP) in 53 patients after remote gastric surgery and Roux-en-Y anastomosis was investigated using a rapid urease test (CU Test) and histology (H&E and Giemsa stain). The pH-value of gastric juice was measured. HP infection of the gastric remnant was found in 56% of 43 patients after partial resection and in no case after total gastric resection. HP-positive and HP-negative patients were comparable in age, sex distribution, indication and technique of gastric operation (except for total gastrectomy with jejunal gastric replacement), intake of acid inhibiting drugs and antibiotics was well as in the presence or absence of a macroscopically visible pathology of the gastric mucosa. On the other hand, the two groups differed in their histological findings, pH value of gastric juice and time interval since surgery. HP infection of gastric remnants is associated with significant glandular atrophy and an additional rise in gastric intraluminal pH compared with HP-negative patients. Both changes may involve an increased risk for gastric cancer. In this report on patients with Y en-Roux operation there is no decrease in gastric HP-colonization with an increasing interval since the time of operation, but rather an increase. This phenomenon seems to depend on the absence of enterogastric reflux. PMID- 1626251 TI - [Livedo reticularis and multiple vascular occlusions in a patient with HLA-B27 negative spondyloarthrosis and antiphospholipid antibodies]. AB - We report the case of a 74-year-old patient with HLA-B27 negative spondylarthropathy presenting with acute disseminated vascular occlusions. The presence of livedo reticularis prompted a search for antiphospholipid antibodies which were found to be markedly elevated. Histopathological examination revealed noninflammatory vascular obstruction. The clinical evolution was rapidly fatal in spite of corticosteroid treatment. Livedo reticularis can be an important diagnostic clue to various types of underlying disease. Increased levels of antiphospholipid antibodies have been associated with thrombosis and thromboembolism, especially in the context of autoimmune diseases such as systemic lupus erythematosus. This paper reports antiphospholipid antibody associated noninflammatory vascular occlusions in a patient with HLA-B27 negative spondylarthropathy. The pathogenetic mechanism of antiphospholipid antibody mediated vascular occlusions is not completely understood and optimal therapy remains to be defined. PMID- 1626253 TI - [Dentistry Europe--the future has begun]. PMID- 1626252 TI - [HIV infection: survey among practicing physicians in Bern]. AB - With increasing numbers of HIV-infected patients, practitioners will play a crucial role in the prevention of HIV infection and in the care of infected persons. To assess the need for accurate education programs we investigated by questionnaire the current practice, attitudes and knowledge of 1057 practitioners (general, internists, surgeons, dermatologists, gynecologists), on care, prevention and treatment of HIV infection and HIV-related problems in the Canton of Berne (population 1 million), Switzerland. 65% of the practitioners provided completely evaluable responses. More than 90% had already prescribed HIV tests by the end of 1989. A majority rejected routinely performed tests (e.g. for all pregnant women, for all patients before surgery). Only about 50% considered a patient's informed consent mandatory before each test. Primary prevention by sexual history-taking was only rarely done in current practice. All recommendations from the Swiss "Stop Aids" campaign were supported, and even experimental measures such as allowing i.v. drug use in street corner agencies or controlled distribution of heroin were supported by the majority. Mandatory testing of risk groups was favored by about 50% but almost nobody wanted to establish name records of persons with risk behaviour. By the end of 1989 about one third of practitioners regularly cared for HIV-infected persons. Most practitioners would prefer to care independently for asymptomatic HIV-infected persons, but would favor a specialist support when caring for symptomatic patients. Lack of medical skills and knowledge was the main reason for their reluctance in caring for patients. Skilled and experienced practitioners were more prone to care for additional patients and were more active in prevention. Knowledge about HIV transmission, HIV-related complications and treatment was good among general practitioners and internists. However, there was some confusion about the indications for active vaccination in Aids patients. The readiness of Bern practitioners to care for HIV-infected persons is already large and could be increased by improving their medical knowledge. However, it is unlikely that more medical information alone will improve their prevention activities. It appears that education programs aimed at improving the prevention activities of practitioners are best designed and performed by their skilled and experienced colleagues. PMID- 1626254 TI - [Dental surveillance and prophylaxis among schoolchildren in the Canton of Geneva between 1980 and 1990]. AB - As in previous years, the dental status of schoolchildren from Geneva has been examined on a yearly basis between 1980 and 1990. A global assessment is presented here, showing a gradual increase in the percentage of caries-free children, especially in kindergarten classes. Moreover, a single evaluation of first permanent molars is presented. PMID- 1626255 TI - [The release of mercury and copper from in vivo aged amalgam fillings]. AB - Release of mercury and copper in water over time from in vivo annealed amalgams in an unpolished and polished state was measured. Mercury and copper loss from unpolished amalgams was on the average 1,00 micrograms/cm2.d and 0.06 micrograms/cm2.d, respectively. Polishing the amalgams reduced these values significantly to 0.19 micrograms/cm2.d for mercury (p = 0.004) and to 0.03 micrograms/cm2.d for copper (p = 0.009). It was concluded that polishing amalgam surfaces (under water cooling) reduces release of mercury and copper significantly. PMID- 1626256 TI - [The factors affecting the risk for the loss of resin-bonded bridges]. AB - 1310 three-unit resin-bonded bridges were examined for their failure rates. After five years 86% (+/- 4%) were still in situ. 64% (+/- 5%) didn't need rebonding. Significant prognostic factors were: preparation of abutments, surface treatment (net retention, silicoating), type of luting agent (Bis GMA) and mobility of the abutments. PMID- 1626257 TI - [The status of the prosthodontic care of poor adults in Zurich]. AB - This study wants to give an overview of the prothetical state of treatment of low income, above-50-year-old patients, who called for examination and treatment at the Cantonal Public Dental Clinic of Zurich. An average of 11.5 own teeth, excluding wisdom teeth, were found among the 151 test persons, whose mean age was 71 years. 30 persons (19.9%) were edentulous. Removable dentures were found significantly more often than fixed reconstructions: 72.5% of the test persons were equipped with removable dentures and 17.2% with fixed bridges. More than 50% of the examined dentures showed hard and/or soft accumulation of plaque and calculus. 43% of the anchor teeth of all partial dentures and 16.3% of all bridge pillars showed carious lesions. About two-thirds of the "denture patients" were not satisfied with their removable denture and wished an adjustment or a new one. These results point out a big need for prothetical treatment among the examined patient group. PMID- 1626258 TI - [Stomatology. Amalgam-associated lichenoid lesions of the oral mucosa]. PMID- 1626259 TI - [Salivary gland and mesenchymal tumors (II). Orofacial neoplasms: their epidemiology, risk factors, prognosis]. PMID- 1626260 TI - [The routine HIV test before surgical interventions]. PMID- 1626261 TI - [The Jura Societe d'Odontostomatologie. Interview by Kurt Venner]. PMID- 1626262 TI - [AIDS]. PMID- 1626263 TI - [3 implant systems are presented]. PMID- 1626264 TI - [A microscopic evaluation of the marginal adaptation of onlays in gold]. AB - The aim of this in vitro trial was to evaluate the marginal seal and adaptation of gold onlays according to the instrumentation used to prepare the bevels, the quality of margins (as cast vs. polished in the laboratory) and two different finishing procedures (burnishing during or after setting of the cement). For that purpose, 25 freshly extracted human molars were restored with onlays using standardized preparation and fabrication methods. The marginal adaptation of the cemented onlays was evaluated using replicas and scanning electron microscopy. The marginal seal was evaluated on sample sections after a dye infiltration test. In order to improve the marginal fit of gold onlay restorations, it can be recommended to: use diamond burs (Intensiv no. 32 and 37) to prepare the bevels finish and polish restorations in the laboratory except for areas with access to clinically burnish, and polish the margins after setting of the cement. PMID- 1626265 TI - [Silicone molding compounds and latex gloves. The effect of latex gloves on addition and condensation silicones]. AB - Inhibited setting of addition silicones has been observed using latex gloves in the dental office. Therefore four addition silicones as well as four condensation silicones were mixed with seven latex gloves with different properties (sterility, powder, accelerator, inner layer). The masses were mixed with bare hands as a control and--additionally--with powdered hands. Condensation silicones stayed unaffected when put together in exact amounts, while some addition silicones showed nearly complete inhibition. Mixing the condensation silicones under the conditions of daily practice--one spoon of body plus a distinct amount of catalyst-resulted in hardness differences compared to using the exact dose. Nevertheless the resulting impressions were of satisfying quality. The powder component (Bio-sorb, Surgikos) leads to an accelerated setting. The general dental practitioner/dental hygienist have to consider these aspects while choosing gloves and silicone putties for taking impressions. PMID- 1626266 TI - [Substance ablation with a superpulsed CO2 laser]. AB - In this study a new, superpulsed CO2-laser was evaluated to remove enamel, dentin and several dental restorative materials. In the first part of the experiment, superpulsed mode was compared with pulsed and continuous wave using semiquantitative test methods. It was found that only superpulse was suitable for the purpose. In the following second part of the experiment, temperature rise, crater depth and crater diameter were quantitated for the superpulsed mode in a range of parameters defined in the first experimental part. It is concluded that superpulsed CO2-laser basically has the potential for a mechanical drill substitute, provided that the output power is limited to about 1 W and short pulses of 0.2-0.3 s duration are applied. In the present form the system is not adapted to clinical use. Cooling of the substrate and flexible beam delivery must be developed. PMID- 1626267 TI - [Tooth root resection and transdental fixation. The flaws and complications]. PMID- 1626268 TI - [Odontogenic tumors. Primary and secondary neoplasms in the jaw area: their epidemiology, prevention and screening]. PMID- 1626269 TI - [Oral-dental care in Africa: utopia or reality?]. PMID- 1626270 TI - [An interview with the representatives of the 3 systems...Branemark, Ha-Ti and Bonefit (ITI)]. PMID- 1626271 TI - [Comments on the paper "Anterior tooth trauma"]. PMID- 1626272 TI - Demand vs. capacity in the healthy pulmonary system. AB - This review examines the lung and chest wall adaptation to exercise in health in persons of widely varying degrees of fitness. First we examine the regulation of breathing and gas exchange in the sedentary young adult who shows a near perfect regulation of alveolar gases, ventilation to perfusion distribution, diffusion equilibrium in the lung during all levels of exercise. This individual's respiratory muscles are also ideally recruited both tonically and phasically so as to meet multi-faceted postural, locomotory and respiratory demands. The topic of plasticity in the pulmonary system is discussed with specific reference to the effects of physical training and athleticism. The key point made here is that both homeostasis of gas transport and mechanical efficiency, with which the pulmonary system meets the demands of muscular exercise will depend upon the ability to maintain a significant margin between demand vs. structural capacity. Pulmonary diffusion capacity and at least some aspects of respiratory muscle function seem to be "overbuilt" in the young untrained adult. This margin of safety no longer prevails as the athlete becomes fitter. The cause is to be found in the relative lack of adaptability of the lung and chest wall to the training stimulus. Examples of demand coming very close or exceeding the capacity of the pulmonary system include the highly trained young endurance athlete and the aged athlete. Examples of "failure" or near failure in the pulmonary system's response to exercise include: a) exercise induced arterial hypoxemia via diffusion limitation; b) diaphragmatic fatigue in endurance exercise; c) expiratory flow limitation at VO2max.; d) achieving the capacity of inspiratory muscles for pressure generation at VO2max. and e) oxygen cost of breathing which is in excess of 15% of VO2max. in those athletes who experience the most mechanical limitation. PMID- 1626273 TI - [Sudden death during performance of sport: forensic medicine elucidation]. AB - Our study deals with cases of sudden death (non-traumatic death) while playing sport which were examined at the Institute of Forensic Medicine at the University of Geneva, and covers the last ten years: 1980-1989. We discovered 19 cases, all men between the ages of 17 to 67. In the case of the younger sportsmen (under the age of 45-50) or when the causes of mortality were unclear, the police requested an autopsy, which totalled 8 cases. In the other 11 cases, we were asked to make an external examination of the bodies, in order to exclude any signs of violence. Seven sportsmen, aged 36-49, who used to play high-risk sports such as football, tennis, basketball and running were autopsied and presented a myocardial infarct. Its interesting that 2 of these cases had also an old scar of a myocardial infarct. The eighth case was a 17 year old boy who had an already known obstructive cardiomyopathy. PMID- 1626275 TI - Publishing is an obligation. PMID- 1626274 TI - [Lactate measurements in sports medicine: comparison of analytic methods]. AB - The measurement of lactate is a major aid for controlling the capacity of an athlete and for establishing individual training schedules. The results are affected by different factors like the site of blood sampling or the distribution of lactate in the blood. The aim of the study was to investigate under constant conditions the results of four different commercially available methods for measuring lactate in blood. All methods were first tested with pure standards of lactate and with different reference sera. Both the accuracy and the reproducibility of the results were good. One method (Lange) showed good accuracy at room temperature but the values were too low at higher temperatures. The enzymatic method was then chosen as reference method for investigations with blood samples. The first method (ESAT) showed excellent correspondence, the results of the second (Lange) were 5-10% too low, and the third method (YSI) showed results too low and were also susceptible to trouble. PMID- 1626276 TI - Improving continuity of care by evaluation of post-discharge outcomes. AB - Evaluation of nursing care is being expanded to identify and assure attainment of patient outcomes. Ideally, evaluation of care will occur throughout all phases of treatment and include perceptions of the patient and/or significant others. A framework for patient outcomes as proposed by Marek (1989) was useful in defining outcomes for newly injured and chronically skin-compromised patients with spinal cord injury. Guidelines established by the Joint Commission for Accreditation of Health Organizations also influenced development of the nursing quality assurance approach. A pilot program demonstrated attainment of expected patient outcomes for high-risk and problem-prone aspects of nursing care. PMID- 1626277 TI - Deafferentation pain after spinal cord injury. Part I. theoretical aspects. AB - Pain which persists long after spinal cord injury can become the most disabling sequela for the survivor. In extreme cases, it may lead to chemical dependency, severe depression and even suicide. Following definition and description of deafferentation pain, the risks and benefits of current pharmacologic, surgical and other therapies are presented. Part I (in this issue) presents theoretical aspects and Part II (in Vol. 9 No. 3) will present management aspects of deafferentation pain. This two-part review is intended to facilitate informed decision-making by both consumers and caregivers. PMID- 1626278 TI - ANA position statements. The role of the registered nurse in the management of analgesia by catheter techniques (epidural, intrathecal, intrapleural, or peripheral nerve catheters). PMID- 1626279 TI - ANA position statements. The role of the registered nurse in the management of patients receiving IV conscious sedation for short-term therapeutic, diagnostic, or surgical procedures. PMID- 1626280 TI - Seronegative inflammatory arthritis in the myelodysplastic syndromes. AB - The myelodysplastic syndromes (MDS) are a group of therapeutically refractory anemias resulting from a clonal stem cell disorder often associated with cytogenetic abnormalities. Immunologic abnormalities and occasionally vasculitis have been reported although no series has characterized an associated arthritis. All cases of MDS diagnosed in 1990 by bone marrow biopsy and followed up at the authors' institution were reviewed. Of the 28 consecutive patients, 8 had acute seronegative inflammatory arthritis temporally related to the initial discovery of cytopenia. Five patients had a symmetric polyarthritis resolving only with use of steroids or upon evolution to leukemia, and 3 had episodes of oligoarthritis with systemic features including fever, pleuritis, pericarditis, and hemolytic anemia. Arthrocenteses in 2 cases did not show crystals or infection. Serological studies were nondiagnostic. The arthritis and systemic features responded to steroids in all 5 treated patients. Inflammatory arthritis appears to be common in MDS. Most compelling is the apparent bone marrow response to steroids in 2 cases, possibly identifying a treatable subgroup. PMID- 1626281 TI - Treatment of psoriatic arthropathy. AB - Psoriatic arthritis develops in 5% of patients with cutaneous psoriasis. Management is similar to that of other chronic inflammatory joint diseases, and the characteristic features of psoriatic arthritis should be considered: the disease is usually mild, with unpredictable flares and remissions, and skin disease is a concomitant feature. Nonsteroidal antiinflammatory agents are the mainstay of therapy and usually provide adequate control. Among long-term treatments, parenteral gold salts, methotrexate, and azathioprine have been shown to be effective. Retinoids are often used in patients with extensive skin lesions. Other treatments are currently being evaluated (auranofin, colchicine, D penicillamine, sulfasalazine, cyclosporine, and gamma-interferon). Antimalarials are difficult to handle and may cause progression of skin lesions. Topical treatments are indicated in every case. Indications depend on the specific features of psoriatic arthritis, the clinical pattern, and the severity of the condition. PMID- 1626282 TI - Dietary fish oil and rheumatic diseases. AB - Dietary fish oil supplementation can induce several metabolic changes relevant to rheumatic diseases. Both experimental and clinical evidence show that dietary fish oil supplementation modulates inflammatory and immune responses. Many studies have shown beneficial, albeit modest, effects in the treatment of rheumatoid arthritis. Studies in murine models of systemic lupus erythematosus have been encouraging, but few studies have been performed to assess the effects of dietary fish oil in the human disease or in other systemic rheumatic diseases. Further study on the efficacy of dietary fish oil supplementation in the treatment of specific rheumatic diseases is warranted. PMID- 1626283 TI - A debate: should patients with rheumatoid arthritis on methotrexate undergo liver biopsies? AB - The question of whether it is appropriate to perform liver biopsies in rheumatoid arthritis patients receiving long-term weekly methotrexate therapy is debated. This debate includes a detailed discussion of the literature to support the debaters' respective views. Points made in favor of biopsy include (1) the significant prevalence of hepatic abnormalities in psoriatic patients; (2) the need to continue administration of the drug to sustain a clinical response; (3) the high incidence of elevations in aspartate amino-transferase, which correlate significantly with hepatic histological outcome; and (4) the fact that the rheumatology community has had relatively short experience with the widespread use of the drug. Arguments against biopsy include (1) the poorly defined specific role of methotrexate in the development of hepatic histological abnormalities; (2) the nonquantitative histological grading system, which makes precise assessment of progression in hepatic disease difficult; (3) the poorly defined role of other factors in the progression of hepatic changes in patients taking methotrexate; and (4) the cost and potential morbidity of the procedure itself. The role of the hepatic Ito cell in the development of fibrosis is also discussed. The protagonists agree on the need to continue studies of liver biopsy tissue from rheumatoid arthritis patients receiving methotrexate to better define this key issue. PMID- 1626284 TI - Fibronectin mediates anchorage-dependent focus formation in cultured human synoviocytes. AB - To determine the effect of extracellular matrix proteins on synoviocyte phenotype, a serum-free, defined-medium culture system was established. Rheumatoid synoviocytes maintained on type I collagen appeared monolayered, whereas cells maintained on fibronectin showed focus formation. Focus formation was abrogated by maintaining cells in the presence of antifibronectin. Focus formation was associated with a fibronectin-rich extracellular matrix, whereas monolayer morphology was associated with matrices containing a greater proportion of collagen. The abundant amount of fibronectin present in the synovial microenvironment may be partially responsible for the transformationlike phenotype displayed by rheumatoid synoviocytes. PMID- 1626285 TI - Analysis of cell populations in rheumatoid arthritis synovial tissues. AB - Knee synovium, taken from patients with rheumatoid arthritis at the time of arthroplasty, was studied immunohistologically. Focal perivascular lymphoid infiltrates of different sizes were examined in detail to evaluate changes in cell populations as the infiltrate size increased. T cells formed the largest component of mononuclear cells of all aggregates. The large grade 3 aggregates contained substantial numbers of B cells arranged around a central venule and cells bearing the CD45RA+ phenotype. In contrast, the small grade 1 aggregates contained few B cells and the T-cell population contained relatively greater numbers of CD8+ cells. Cells bearing the CD45RO+ phenotype exceeded CD45RA+ cells in grade 1 aggregates. Detailed analysis of mononuclear cell aggregates of different sizes in the rheumatoid synovium suggests that the composition of each aggregate depends on the total number of mononuclear cells it contains. PMID- 1626286 TI - Aging of the human synovium: an in vivo and ex vivo morphological study. AB - Age-associated changes of the human synovium have been investigated by microarthroscopy, optical and electron microscopy, immunohistochemistry, and cytochemistry. The knee joints of nineteen 15- to 56-year-old subjects, classified as normal by inspection, were carefully examined by microarthroscopy; small synovial tissue biopsy specimens from both the suprapatellar pouch and the medial tibiofemoral gutter were taken. Microarthroscopy showed that the villi were more numerous and the vascular network and cell distribution and profiles less regular in aged individuals. These data were confirmed by scanning electron microscopy, which also showed large areas of the synovial surface devoid of cells and collagen bundles in contact with the joint cavity in aged subjects. Light and transmission electron microscopy confirmed these data and allowed evaluation of the number, distribution, shape, and internal organization of cells as well as the distribution of vessels and the organization of the extracellular matrix in the full thickness of the synovium (down to 2 mm). Particular attention was paid to synovial lining cells, among which three main phenotypes could be recognized: synthetic type (present at all ages and hypertrophied in aged subjects), macrophagelike (increasing with age), and fibroblastlike. Collagen increased with age. Further studies are needed for comprehensive understanding of age-associated changes in the human synovium. PMID- 1626287 TI - The use of intravenous gadopentetate dimeglumine in magnetic resonance imaging of synovial lesions. AB - Spin echo T1- and T2-weighted images and intravenously administered gadopentetate dimeglumine-enhanced T1-weighted images were obtained in 4 normal volunteers and 11 patients (11 joints) with painful, intermittent, or persistent joint swelling of unknown etiology. These studies were retrospectively reviewed to assess the benefits of contrast-enhanced magnetic resonance imaging (MRI) in evaluating the synovium. Normal synovium and joint fluid showed no visually apparent enhancement on images obtained immediately after intravenous injection of gadopentetate dimeglumine. Abnormal synovium enhanced significantly, allowing the precise identification of equivocal or unsuspected synovial disease processes. These results suggest that, in selected cases, enhanced MRI can be a useful adjunct in the evaluation of suspected synovial disease processes. PMID- 1626288 TI - The geography of coracoclavicular joints. AB - On the basis of published anatomical and skeletal anthropological surveys supplemented by published and unpublished commissioned radiologic surveys, the distribution of coracoclavicular joints in the world is described. The findings are in keeping with a focus having developed in central Asia in Pleistocene times. Thus, this anatomical variant can serve, by regression, as a marker for population migration from prehistoric times to the present. PMID- 1626289 TI - Pathology of osteonecrosis of the femoral head. A review of experience at the Hospital for Joint Diseases, New York. AB - Pathological examination of the resected femoral heads from approximately 2000 total hip replacement operations carried out at the Hospital for Joint Diseases from 1984 to 1989 identified the presence of osteonecrosis in 345 patients (377 femoral heads). In 232 patients the osteonecrosis, referred to as "idiopathic," had occurred in the absence of a subcapital fracture. The present paper describes the pathology of the necrotic lesions in these 232 patients. The use of undecalcified sections and microradiography provides evidence of bone marrow calcification which, at the margin of the lesion, is sufficient to influence the radiographic features of the lesion significantly. Although a subchondral fracture is an almost constant feature of osteonecrosis when it occurs in a femoral head with a normal articular cartilage, no such fracture was found in cases in which osteonecrosis had occurred in an osteoarthritic joint. PMID- 1626290 TI - The lateral approach for hip arthrography. AB - Despite advances in imaging techniques, hip arthrography is still a useful diagnostic tool. We have found that the lateral approach to the hip joint, with the needle inserted superior to the greater trochanter and parallel to the table top under fluoroscopic control, allows easy advancement of the needle into the lateral hip joint space. PMID- 1626291 TI - Quantitative early phase scintigraphy in the prediction of healing of tibial fractures. AB - Imaging with technetium-99m methylene diphosphonate (99mTc-MDP) is established in the diagnosis of infection, neoplasia and ischaemic necrosis in orthopaedic practice, but its role in fracture healing is less well-defined. Previous studies have shown a relationship between fracture site activity (region A), activity in adjacent normal bone (region C) and time to union. The predictive value of the A/C ratio of the image obtained 300-800 s after injection was assessed in a prospective study of 50 patients with closed tibial fractures managed with plaster casts, external fixators and intramedullary nails. There were significant differences in absolute uptake and A/C ratio between the three groups (P less than 0.05), but this was not related to time to union. Reamed nailing alters the distribution of 99m-Tc-MDP uptake so as to reduce the A/C ratio (1.10 +/- 0.20), but there is a promising role for early phase bone scanning in non-operative (A/C = 1.40 +/- 0.21) or externally fixed (A/C = 1.26 +/- 0.22) fractures in conjunction with other non-invasive methods of monitoring the biomechanical environment. PMID- 1626292 TI - Degenerative disc disease in the lumbar spine: another cause for focally reduced activity on marrow scintigraphy. AB - A patient is presented in whom a focal reduction in marrow activity in the lumbar spine on both leucocyte and nanocolloid marrow scintigraphy was subsequently shown to be due to fatty infiltration of marrow in association with disc degeneration. Degenerative disease in the lumbar spine has not been previously described as a cause of abnormal bone marrow distribution by such means and needs to distinguished from a more serious pathology, such as malignant infiltration and vertebral infection, which it may mimic. In a retrospective review of 33 nanocolloid bone marrow and 117 leucocyte scintigrams, 8 showed a degree of reduced marrow activity in the lumbar spine consistent with that caused by degenerative changes. PMID- 1626293 TI - Case report 713. Chondromyxoid fibroma of the third metatarsal. AB - In the case presented, the imaging features are those of an aggressive benign or less aggressive malignant lesion. The differential diagnosis radiographically included aneurysmal bone cyst with or without an accompanying lesion, giant cell tumor synovial sarcoma, and other mesenchymal sarcomas. Indeed, at times it is difficult to be certain whether the process originated in the bone or soft tissue. Pathological examination of the resected specimen showed the typical features of chondromyxoid fibroma. Grossly, the tumor was well demarcated and firm and composed of tan, translucent tissue that destroyed cortex but was confirmed by periosteum. Histologically, the tumor consisted of myxoid, chondroid, and fibrous elements. The tumor lobules were composed of predominately myxoid matrix containing stellate cells. Variable chondroid elements were present with immature appearing chondrocytes, containing eosinophilic cytoplasm and irregularly shaped nuclei. PMID- 1626294 TI - Case report 729. Myositis ossificans and aneurysmal bone cyst. AB - This is the first reported case of ABC in a reactive lesion of soft tissue. The ABC may be regarded as an unusual type of organization of hematoma encountered in a bone-producing milieu. This would support the current concept that ABC occurring in association with another condition represents a secondary change in a pre-existing lesion. PMID- 1626295 TI - Case report 730. Malignant large cell lymphoma of tibial epiphysis. AB - We present a case of primary lymphoma of bone arising in the proximal tibial epiphysis of a 16-year-old boy. To the best of our knowledge, primary lymphoma of bone has not been described previously as a mimicker of chondroblastoma. This case report is intended to increase awareness among clinicians and radiologists that primary lymphoma of bone can present with a long clinical prodrome and initially benign radiographic appearance. Early recognition of this unusual presentation will (hopefully) increase the likelihood of cure. However, it is recognized that in children, primary lymphoma of bone is a rare diagnosis and associated with a poor prognosis unless aggressive treatment is utilized [8]. PMID- 1626296 TI - Case report 731. Complicated Baker's cyst. AB - The atypical appearance of a gas-containing, noninfected, popliteal synovial cyst has been presented. The case again demonstrates the value of plain radiographs, in this instance in distinguishing gas bubbles and calcification, which may not be apparent by MRI and ultrasound. The uniqueness of this case is stressed. The cause of the gas bubbles was not ascertained. PMID- 1626297 TI - Case report 732. Gout presenting as a large pseudo tumor (tophus) in the proximal end of the tibia. AB - A case of a large, lytic, tophaceous defect in the upper end of the tibia has been reported in a 44-year-old man as a solitary lesion. The term "gouty tophus" should not be confused with the geode or subchondral bone cyst. PMID- 1626298 TI - Case report 733. Calcific tendinitis of the origin of the medial and lateral heads of the rectus femoris muscle and the anterior iliac spin (AIIS). AB - Calcific tendinitis at the site of origin of the rectus femoris muscle is a rare lesion. Presumed to be formed by deposition of hydroxyapatite crystals, this entity may be confused with other lesions such as os acetabuli or posttraumatic abnormalities. The characteristic location and appearance of the calcifications in a symptomatic patient with no history of trauma should allow diagnosis and subsequent symptomatic therapy. PMID- 1626299 TI - Case report 734. Fibroma of tendon sheath eroding 3rd metatarsal bone. AB - A case is presented of a 37-year-old man with an extrinsic lesion originating in the soft tissue adjacent to the 3rd metatarsal and smoothly eroding the adjacent bone. The operatively confirmed diagnosis of fibroma of tendon sheath was surprising, giant cell tumour of tendon sheath eroding bone being considerably more common; these two lesions are normally impossible to distinguish radiologically. PMID- 1626300 TI - Case report 735. Vertebral osteosarcoma. AB - A case of OS of the T6 vertebra in a 58-year-old man is presented. Diagnosis was obtained by an open biopsy. The clinical and radiographic findings were described. The topic of vertebral OS was discussed at length. We emphasize the fact that OS of the spine is rare and that those cases not associated with Paget's disease or previous radiation therapy are even rarer. PMID- 1626301 TI - Effect of lumbar orthosis on intervertebral mobility. A roentgen stereophotogrammetric analysis. AB - To determine the stabilizing effect of external lumbar supports on the intervertebral mobility in the lower lumbar spine, seven patients with a posterolateral lumbosacral fusion without internal fixation were examined by roentgen stereophotogrammetric analysis in supine and erect positions 1 month after surgery, that is, after soft tissue healing but before fusion consolidation. Each patient was examined without lumbar support, with a molded, rigid orthosis and with a canvas corset with molded, plastic posterior support. Neither of the two types of lumbar support had any stabilizing effect on the sagittal, vertical, or transverse intervertebral translations. This study using roentgen stereophotogrammetric analysis confirms that lumbosacral orthosis has effect by restricting gross motions of the trunk rather than intervertebral mobility in the lumbar spine. PMID- 1626302 TI - An improved method of stature measurement for quantitative determination of spinal loading. Application to sitting postures and whole body vibration. AB - A refined procedure for measuring stature is described; this provides a reproducibility error of 0.4 mm. The procedure accommodates the natural diurnal change in stature and permits estimation of the net stature change caused by a change in spinal loading. A series of measurements done with a cohort of 20 young and middle-aged persons showed that stature decrease was related linearly to the quasi-static load on the spine. The coefficient of proportionality between load and height loss was inversely proportional to the cross-sectional area of the lumbar discs. This method was used to investigate sitting postures and whole-body vibration to demonstrate the applicability of the procedure to quantify spinal strain (and, therefore, estimate comparative loading) in applied ergonomics. Sitting invariably led to an increase in stature, regardless of the type of chair used or the posture maintained. Whole-body vibration did not induce any loss of stature. Thus, this novel approach was able to enhance understanding of spinal behavior under different loading conditions. PMID- 1626303 TI - Human facet cartilage: swelling and some physico-chemical characteristics as a function of age. Part 1: Swelling of human facet joint cartilage. AB - The hydration of cartilage from human facet joints was measured after the joints had been subjected to different treatments. One group of facets was opened and directly exposed to physiologic saline solution before extraction of cartilage plugs. The plugs were weighed, re-equilibrated in fluid, and weighed again. The swelling results obtained under these conditions were compared with those when similar plugs of cartilage were excised from joints that had not been exposed to solution or had been exposed to solution while still closed. It was found that swelling was least (and similar in value to hip cartilage) for joints that had been exposed open to saline solution, highest for joints that had not been exposed to solution, and intermediate for joints that had been exposed to solution while still closed. The same trends were observed whether the cartilage on the joint was intact or fibrillated, although in each group the swelling and the final hydration were higher for fibrillated than for intact tissue. It was concluded that facet cartilage, unlike human hip or knee cartilage, is underhydrated when excised from the joint. This underhydration is thought to reflect the permanent presence of stresses in vivo on some part of the facet joints, the position of the loaded site changing with time. The authors attempted to distinguish between the swelling caused by this underhydration and that from disruption of the collagen network in the case of fibrillated specimens. PMID- 1626304 TI - Implants of heterologous demineralized bone matrix for induction of posterior spinal fusion in rats. AB - The authors tested the osteoinductive capacity of powdered heterologous (bovine) demineralized bone matrix in rats. The first part of the study concerned a monolateral posterior spinal implant after decortication of three vertebrae, using as a control area the animal's contralateral side, in which neither bone graft nor any other material were placed. In another group of rats, a comparative evaluation was made of powdered heterologous demineralized bone matrix and fresh autologous bone. In the same animal, autologous bone was implanted to realize a thoracic posterior fusion and demineralized bone matrix, to induce a posterior fusion in the lumbar area. All data obtained suggested a good osteoinductive activity of heterologous powdered demineralized bone matrix. The two posterior spinal fusions done in the same animal with heterologous demineralized bone matrix or autologous bone, respectively, had similar callus development and required the same time for formation. PMID- 1626305 TI - Pulmonary function after spinal surgery for idiopathic scoliosis. AB - Respiratory function was assessed in 20 patients with idiopathic scoliosis undergoing spinal surgery (median age, 15 years; range, 11-34 years; median preoperative vital capacity, 67%; range, 28-109% predicted). Ten patients underwent anterior spinal surgery through a thoracotomy incision, seven of whom had posterior spinal surgery as a second-stage procedure. The other ten had posterior spinal surgery as their initial operation. Postoperatively, three patients had clinical evidence of respiratory complications. Daytime oxygen saturation was reduced throughout the first postoperative week, with no significant difference between anterior and posterior spinal surgery. Hypercapnia was unusual and generally mild. Vital capacity was reduced significantly 1 week after both anterior and posterior spinal surgery (P less than 0.05). The median vital capacity 1 week after anterior spinal surgery was 45% of preoperative values compared with 78% after posterior surgery (P less than 0.05). Inspiratory muscle strength, as assessed by sniff mouth pressure, was 56% of preoperative values 1 week after anterior spinal surgery (P less than 0.05) and 85% after posterior spinal surgery (not significant). Vital capacity, but not sniff mouth pressure, remained significantly reduced 6 weeks after surgery. Oxygen saturation should be monitored noninvasively during the first week after both anterior and posterior spinal surgery even in patients at low risk of developing respiratory complications. PMID- 1626306 TI - Respiratory failure in scoliosis and other thoracic deformities. A survey of patients with home oxygen or ventilator therapy in Sweden. AB - Registers covering Swedish patients with home ventilator or long-term oxygen therapy were used to study respiratory failure caused by thoracic deformities. In all, 107 patients were studied. Postpolio scoliosis was found in 47 patients. The age of starting therapy varied between 28 and 80 years. Fourteen patients had thoracic deformities other than scoliosis. The mean scoliotic angle was 135 degrees among the patients with scoliosis, and the mean vital capacity was 26% (range, 13-54%) of predicted normal. The yearly demand for home ventilator or oxygen therapy is calculated to three per million inhabitants. No operated patients had respiratory failure, and no patients were found with idiopathic scoliosis and respiratory failure younger than 30 years of age, which may indicate a preventive effect of corrective surgery on the development of respiratory failure. PMID- 1626307 TI - Spinal extradural angiolipoma. Case report and review of the literature. PMID- 1626308 TI - Hemolysis after laminectomy. A case report. PMID- 1626309 TI - Radiologic interpretation of lumbar vertebral rotation. PMID- 1626310 TI - Possible functions of a new genetic marker in central nervous system: the sulfated glycoprotein-2 (SGP-2). AB - This brief review discusses the recent characterization in the brain of a gene coding for a protein that may be involved in programmed cell death and/or brain plasticity. We will term it sulfated glycoprotein-2 (SGP-2), the name corresponding to the first cDNA characterized. Recent studies have demonstrated the overexpression of this sulfated glycoprotein in various CNS disorders, such as certain gliomas, Alzheimer's disease and epilepsy, as well as after experimental brain injury in animals where different cell types were undergoing tissue remodelling or cell death. In peripheral tissues, SGP-2 gene expression has been found to be strikingly increased following experimental manipulations in which cells of injured tissues were undergoing programmed cell death or apoptosis. The results reported thus far are intriguing and suggest the possible involvement of SGP-2 in apoptotic mechanisms as well as its interaction with components of the immune system possibly associated with cell death in neurodegenerative disorders. PMID- 1626311 TI - Effects of nigrostriatal lesions on the levels of messenger RNAs encoding two isoforms of glutamate decarboxylase in the globus pallidus and entopeduncular nucleus of the rat. AB - The neurotransmitter gamma-aminobutyric acid (GABA) is present in efferent neurons of the striatum and of the pallidum, one of the main striatal target areas. Dopaminergic nigrostriatal neurons play a critical role in the regulation of GABAergic neurotransmission in the striatum. In the present study, we investigated their role in the regulation of glutamate-decarboxylase (GAD) mRNA expression in two divisions of the pallidum in rats: the globus pallidus and entopeduncular nucleus, equivalent to the external and internal pallidum, respectively, of primates. Dopaminergic neurons were lesioned by unilateral injections of 6-hydroxydopamine (6-OHDA) in the substantia nigra of adult rats. Two or 3 weeks after the lesion, frontal cryostat-cut sections of the brain were processed for in situ hybridization histochemistry with 35S-labeled RNA probes synthesized from cDNAs encoding two distinct isoforms of GAD of respective molecular weight 67,000 (GAD67) and 65,000 (GAD65). The number of labeled cells was determined, and intensity of labeling in individual cells was analyzed by computerized image analysis on emulsion radioautographs. In the globus pallidus, the number of labeled neurons and intensity of labeling per cell were increased on the side ipsilateral to the lesion as compared with control rats in sections hybridized with the GAD67 RNA probe. No changes were detected on the side contralateral to the lesion or in the levels of labeling for GAD65 mRNA. Confirming previous data, the level of labeling for GAD65 mRNA was much higher than for GAD67 mRNA in the entopeduncular nucleus of control rats. In rats with a 6-OHDA lesion, labeling for both GAD67 and GAD65 mRNAs was decreased on the side contralateral, but not ipsilateral, to the lesion, as compared with control rats. The results show that lesions of the nigrostriatal pathway in rats affect the levels of mRNAs encoding two distinct isoforms of GAD in neurons of the globus pallidus and entopeduncular nucleus differently. In addition, results in the entopeduncular nucleus further support a bilateral effect of unilateral dopaminergic lesions. PMID- 1626312 TI - Calcium-, calcium/calmodulin-, and calcium/phospholipid-stimulated protein phosphorylation in the rat anterior pituitary. AB - Calcium-dependent protein phosphorylation may be a critical step in the stimulated secretion of anterior pituitary hormones. We have noted the existence of a number of calcium-calcium/calmodulin-, and calcium/phospholipid-dependent phosphoproteins in the normal rat anterior pituitary. Cell extracts were prepared from anterior pituitary glands of male rats and phosphorylated with [gamma 32P]ATP in the presence or absence of calcium, calmodulin, and phosphatidylserine. The samples were electrophoresed on SDS-PAGE gels, autoradiographs prepared, and phosphate incorporation into specific proteins quantitated with microdensitometry. Calcium alone significantly stimulated the phosphorylation of proteins with molecular weights of 80.0-, 62.0-, 51.0-, 30.5-, and 25.0-kDa. The phosphorylation of 21.5-, 51.0-, and 80.0-kDa MW phosphoproteins was found to be phospholipid dependent. The phosphorylation of 62.0-, 51.0-, 33.0-, 30.5-, and 25.0-kDa MW phosphoproteins was found to be calcium/calmodulin kinase dependent. Calcium/calmodulin also inhibited phosphorylation of the 80.0-kDa phosphoprotein. PMID- 1626313 TI - MK-801 protection against methamphetamine-induced striatal dopamine terminal injury is associated with attenuated dopamine overflow. AB - Repeated administrations of methamphetamine (m-AMPH) produce high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. Pharmacological blockade of N-methyl-D-aspartate (NMDA) receptors has been shown previously to prevent m-AMPH-induced striatal DA terminal injury, but the mechanism for this protection is unclear. In the present study, in vivo microdialysis was used to determine the effects of blockade of NMDA receptors with the noncompetitive antagonist MK-801 on m-AMPH-induced striatal DA overflow. Four injections of MK-801 (0.5 mg/kg, ip) alone did not significantly change extracellular striatal DA concentrations from pretreatment values. Four treatments with m-AMPH (4.0 mg/kg, sc at 2-hr intervals) increased striatal DA overflow, and the overflow was particularly extensive following the fourth injection. This m-AMPH regimen produced a 40% reduction in striatal DA tissue content 1 week later. Treatment with MK-801 15 min before each of the four m-AMPH injections or prior to only the last two m-AMPH administrations attenuated the m AMPH-induced increase in striatal DA overflow and protected completely against striatal DA depletions. Other MK-801 treatment regimens less effectively reduced the m-AMPH-induced striatal DA efflux and were ineffective in protecting against striatal DA depletions. Linear regression analysis indicated that cumulative DA overflow was strongly predictive (r = -.68) of striatal DA tissue levels measured one week later. These findings suggest that the extensive DA overflow seen during a neurotoxic regimen of m-AMPH is a crucial component of the subsequent neurotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626314 TI - Regional norepinephrine response to amphetamine using dialysis: comparison with caudate dopamine. AB - The response of extracellular norepinephrine to the acute administration of amphetamine was assessed, using dialysis, in prefrontal cortex and hippocampus in awake, behaving rats. Norepinephrine exhibited a pronounced and rapid dose- and time-dependent increase in response to 0.5 and 2.5 mg/kg amphetamine, which corresponded closely to the time course of the behavioral profile. These results are consistent in with a possible role for norepinephrine in the behavioral response to amphetamine. PMID- 1626315 TI - Distribution of enkephalin and its relation to serotonin in cat and monkey spinal cord and brain stem. AB - The distribution of enkephalin (ENK)-like immunoreactivity (LI) in spinal cord and medulla oblongata of cat and gray monkey (Macaca fascicularis) was studied by use of immunofluorescence and peroxidase antiperoxidase (PAP) techniques. Possible coexistence between ENK- and 5-hydroxytryptamine (5-HT)-LI was also analyzed with double labeling immunofluorescence. Furthermore, in situ hybridization was used to demonstrate cell bodies in the brain stem expressing mRNA encoding for ENK. ENK-immunoreactive (IR) axonal varicosities and fibers were demonstrated throughout the spinal cord gray matter, with the highest density in the superficial dorsal horn, the area around the central canal, the intermediolateral cell column, the sacral parasympathetic nucleus, and in Onuf's nucleus. In the monkey ventral horn, ENK-IR varicose fibers could in some cases be demonstrated in very close apposition to cell bodies. A low degree of co localization between ENK- and 5-HT-LI was seen in the spinal cord of both species. Still, fibers containing both compounds could as a rule be demonstrated in every section studied. The highest degree of coexistence was encountered in the motor nucleus of the ventral horn. Six weeks after a low thoracic spinal cord transection a decreased staining for ENK-LI was demonstrated in the ventral horn motor nucleus, whereas other parts of the spinal cord appeared unaffected. In the brain stem of cats after colchicine treatment, ENK-LI was found in a majority of the 5-HT-IR cell bodies in the raphe nuclei (nucleus raphe magnus, pallidus and obscurus) and in the lateral reticular nucleus (rostroventrolateral reticular nucleus). In cat not pretreated with colchicine, a few weakly stained ENK-IR cell bodies could be found in the midline raphe nuclei and in the lateral reticular nucleus with the PAP technique. In the monkey brain stem without colchicine treatment, using the PAP technique, heavily stained ENK-IR cell bodies could be seen in the lateral reticular nucleus whereas, as in the cat, only a few, weakly stained ENK-IR cell bodies could be seen in the midline raphe nuclei. Using in situ hybridization technique, ENK mRNA expressing cells were demonstrated in the lateral reticular nucleus while no convincing mRNA signal could be found over cell bodies in the raphe nuclei. It is concluded that part of the ENKergic innervation of the cord in both species derives from supraspinal or suprasegmental levels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1626316 TI - [Results of studies with aborted cattle fetuses]. AB - The laboratory of the Animal Health Service of South Holland investigated 2410 cases of spontaneous abortion (twins (112) were considered one case). Seventy eight afterbirths without foetuses were also examined. The aim of the study was not only to find the cause of abortion but also to see whether there was a relation between the results of the different bacteriological, virological and histological tests used. The presence of IgG in the blood of foetuses older than 5 months was also determined. A micro-organism was isolated from 25% of the foetuses. On the basis of results of other tests, it is probable that microbial infection played a role in a further 21% of the abortions. BHV was isolated in 2.5% of the cases. Actinomyces pyogenes was found in 6% of the foetuses and fungi in 3.5%. More infections with Actinomyces pyogenes, Listeria monocytogenes and fungi were observed when the cattle were kept indoors. It is emphasised that both foetuses as well as placental membranes should be examined, and both foetuses of twins. In stable enzooties in the Netherlands, the following infections should be taken into consideration: Brucella abortus, BHV, BVD, Chlamydia psittaci and Leptospira hardjo. The authors stress the need for a more standardised approach to research, the more so because the results could have consequences not only for monitoring activities (checks for Br. abortus) but also for liability. PMID- 1626317 TI - [A horse with osteochondrosis. Now what?]. AB - Based on three clinical cases, the history and the clinical and radiological aspects of osteochondrosis in horses are discussed. The prognosis, therapy and consequences with regard to athletic soundness and use for breeding are described. PMID- 1626318 TI - [Spirit and animal]. PMID- 1626319 TI - [Complementary testing criteria for veterinary drugs applied in animals for choice meat production. Recommendations by the Drug Advisory Commission of the Royal Dutch Society for Veterinary Medicine]. PMID- 1626320 TI - Gene expression in Echis carinatus (carpet viper) venom glands following milking. AB - RNA was extracted from the venom glands of Echis carinatus at different times after milking, and the temporal pattern and nature of mRNA transcribed during venom regeneration was examined by in vitro translation. Venom products were immunoprecipitated with E. carinatus venom polyclonal antiserum. Maximum transcriptional activity occurred 3 days after milking. Electrophoretic analysis of the translation products showed minimal differences in the banding patterns at each time interval. Analysis of the translation products from Kenyan, Nigerian and Saudi Arabian carpet vipers, however, revealed differences which suggest that the observed heterogeneity in E. carinatus venom occurs at the level of the genome. PMID- 1626321 TI - Effects of myotoxin alpha on fusion and contractile activity in myoblast-myotube cell cultures. AB - Cultured myoblasts and moytubes were used to study the effects of purified myotoxins from rattlesnake venoms. Standard cell culture techniques were used to establish and maintain primary cultures derived from neonatal rat tissue and two clonal cell lines, rat RMo cells and mouse C2 cells. Toxin concentrations, ranging from 0.04 to 1.0 microM, were added to the cultures at various times under distinct, well-defined conditions. Addition of myotoxin alpha to primary myoblast cultures did not appear to affect the fusion process, whereas similar experiments with two clonal cell lines produced larger myotubes when contrasted with untreated control cultures, particularly with RMo cells. The myotubes derived from primary cell cultures twitched spontaneously but the twitching ceased when the medium was replaced with a serum-free chemically defined incubation medium. Addition of myotoxin alpha to the primary myotubes incubated with serum-free defined medium caused the myotubes to twitch again. Derivatives of myotoxin alpha were prepared by reactions with tetranitromethane and with iodoacetic acid, the latter under reducing and non-reducing conditions. The resulting products, purified but not chemically characterized, were nearly devoid of activity when primary cultures were used to test activity. PMID- 1626322 TI - Antibodies to brevetoxin B: serologic differentiation of brevetoxin B and brevetoxin A. AB - A brevetoxin B immunogen was prepared by reacting brevetoxin B with the amino groups of bovine albumin followed by treatment with sodium borohydride. Immunized rabbits produced antibodies that bound [3H]brevetoxin B-alcohol. This binding increased with repeated immunization (KD for one rabbit after three courses of immunization was about 10 pM). Brevetoxin B inhibited greater than 500 times more effectively than brevetoxin A. When tested in a competitive binding assay with [3H]brevetoxin B-alcohol-brevetoxin B antibody, the alcohol was six times more effective as an inhibitor than brevetoxin B. Despite some similarities in structure with brevetoxin A, the antibodies to brevetoxin B did not recognize the backbone of brevetoxin A. PMID- 1626323 TI - Sensitivity in culture of epithelial cells from rhesus monkey kidney and human colon carcinoma to toxins A and B from Clostridium difficile. AB - The effect of toxins A and B from Clostridium difficile on human colon carcinoma cells (HT-29, epithelial), rhesus monkey kidney cells (MA-104, epithelial) and green monkey kidney cells (VERO, fibroblast) was studied. Both toxins caused rounding of HT-29 cells and rounding with projections remaining attached to the substrate in MA-104 and VERO cells; however, the sensitivity to each toxin varies considerably. Toxin A was detected in ng by VERO, pg by HT-29 and fractions of pg by MA-104 cells; for toxin B, pg were detected by VERO, ng by MA-104 and micrograms by HT-29 cells. HT-29 cells were grown with galactose to allow their differentiation to enterocytes, and their sensitivity to the toxins during the process was studied. At early stages, the sensitivity to both toxins was similar, and as the differentiation proceeded, the response to both toxins decreased continuously, and after 16 days no evident morphological effect was observed, even with micrograms amounts of either toxin. In contrast to all cell lines reported to date, HT-29 and MA-104 epithelial cells are exquisitely sensitive to toxin A and less responsive to toxin B. The rounding of HT-29 by these toxins depends on the degree of differentiation of the cell. PMID- 1626324 TI - Hemorrhagic, fibrinogenolytic and edema-forming activities of the venom of the colubrid snake Philodryas olfersii (green snake). AB - The venom of P. olfersii has high hemorrhagic, edema-inducing and fibrin(ogen)olytic activities. It is devoid of thrombin-like, procoagulant, phospholipase A2 and platelet aggregating enzymes. The main activities are metalloproteinases inhibited by metal chelators (EDTA and 1,10-phenanthroline) and sulfhydryl compounds (DTT and cysteine). The hemorrhagic and fibrinogenolytic enzymes were partially purified by gel filtration on HPLC. The hemorrhagic activity of the venom was neutralized by commercial horse antivenoms to Bothrops species, as well as by rabbit antisera specific for hemorrhagic factors isolated from these Bothrops venoms. No immunoprecipitin reactions were obtained, indicating that the few epitopes of the P. olfersii hemorrhagin are involved in these neutralization reactions. The fibrinogenolytic enzyme cleaves A alpha-chain more quickly than the B beta-chain of human fibrinogen. The venom also solubilizes fibrin. This solubilization appears to occur from the hydrolysis of unpolymerized alpha-chain and cross-linked gamma-gamma dimer. The fibrin peptide products are distinct from those produced by plasmin. PMID- 1626325 TI - Activity of sarafotoxin/endothelin peptides in the heart and brain of lower vertebrates. AB - The effects of sarafotoxin-b (SRTX-b) and endothelin-1 (ET-1) were tested in the fish tilapia (Ore niloticus x O. aureus hybrids) and torpedo (Torpedo ocellata), the toad (Bufo viridis), the agama lizard (Agama stellio) and water snake (Natrix tessellata). In isolated heart preparations of the fish and agama, peptide doses of 0.05-0.5 micrograms/ml induced positive inotropic effects, reduction of the contraction rate and arrhythmia, leading to cardiac arrest. In the toad, a negative inotropic effect and a reduction of the contraction rate were observed, whereas the water snake was hardly affected by either SRTX-b or ET-1. In the agama, an i.v. injection of 15 micrograms of SRTX-b caused changes in the ECG, culminating in A-V block that led to cardiac arrest, while in the toad an injection of 45 micrograms induced only transient disturbances in the ECG. Binding studies with 125I-SRTX-b revealed specific binding sites for SRTX-b and ET-1 in the heart and brain preparations of fish (tilapia and torpedo) and agama, whereas no specific binding could be demonstrated in the toad or in the snake. These results suggest that most vertebrates tested are sensitive to SRTX/ET, while the snake may possess receptors that are of a different structure. PMID- 1626326 TI - Factors associated with the mass of venom expended by prairie rattlesnakes (Crotalus v. viridis) feeding on mice. AB - The purpose of this study was to assess through correlation analyses the various factors and consequences associated with the mass of venom injected by prairie rattlesnakes (Crotalus v. viridis) into their natural prey, deer mice (Peromyscus maniculatus). Fifty-seven predator-prey interactions were studied via slow motion videotape review. The mass of venom expended by snakes during biting was quantified by enzyme-linked immunosorbent assay (ELISA) of whole-animal homogenates. The quantity of venom expended was not related to size of prey; however, the range of mouse sizes (13-31 g) was quite narrow. Multiple bites of the same mouse were not associated with incremental increases in venom expenditure; only about 40% more venom was expended by striking prey a second time. The duration of fang contact and site of fang penetration had no discernible effects on venom expenditure. The site of fang penetration of prey appeared to be random, due to evasive actions of the mice. The components of striking (duration of launch, fang contact, and recoil, respectively) and distance of the strike were correlated and appeared to be influenced by the prey's reaction. After striking and releasing mice, the snakes did not attempt to relocate more quickly those prey which succumbed to venom relatively quickly. Both natural (snakebite) and artificial (syringe) injections indicated that the site of venom injection (e.g. anterior, posterior, muscle, vital organ) has a greater influence on subsequent mobility and survival of mice than the quantity of venom injected. It appears that some behavioral aspects of predation (especially the sequential components of striking) are flexible and responsive to prey reactions, while others (venom expenditure and poststrike immobility) are less subject to modification. PMID- 1626327 TI - Citrate is a major component of snake venoms. AB - Citrate has been identified as a major component of snake venoms by gas liquid chromatography and mass spectrometry. The venoms of Bothrops asper, Crotalus atrox, Crotalus viridis viridis, Crotalus adamanteus, Sistrurus miliarius barbouri, Crotalus horridus horridus, Agkistrodon contortrix mokasen, Agkistrodon contortrix contortrix and Agkistrodon piscivorus piscivorus contain citrate at concentration levels which can serve as effective buffers. Calcium, magnesium, zinc, iron, sodium and potassium salts of citrate would be constituents of venom. PMID- 1626329 TI - Bibliography of toxinology. PMID- 1626328 TI - A new bioassay reveals mollusc-specific toxicity in molluscivorous Conus venoms. AB - Contraction of the foot pedal of a limpet snail is described as a new and quantifiable bioassay for mollusc paralysis. This bioassay was used for screening the venoms of seven different species of Conus snails. Comparison of the results of the limpet assay with those obtained from fish and blowflies shows a correlation between the feeding specificities and venom toxicities of these Conidae. The limpet bioassay should be useful for identification and monitoring of the purification of new toxins active on molluscan systems. PMID- 1626330 TI - Creativity, depression and suicide. AB - The relationship between suicide and creativity has long been a subject of considerable concern. The author presents evidence indicating that in fact depression, suicide, and creativity are related. Several hypotheses for the relationship are posited. It is suggested that the same changes in the serotonergic system that are associated with depression in general and with impulsive suicides and homicides in the extreme may also be responsible for an element of risk taking that characterizes creativity and innovation in a person psychodynamically predisposed to being creative. PMID- 1626331 TI - Identification of coping ideation and strategies preventing suicidality in a college-age sample. AB - This study attempts to identify coping mechanisms relevant to the prevention of progressive lethality in suicidal behavior among youth. College students (N = 296) aged 18 to 24, self-identified as having no past suicidal ideation, mild ideation, severe ideation, or having attempted suicide, completed the Reasons for Living Inventory (Linehan, Goodstein, Nielson, & Chiles, 1983), a similarly derived instrument for age-specific coping cognitions, and a scale of coping strategies for diminishing suicidality. Discriminant functions analyses of the mean factor scores for each scale were used to assess the pertinence of various coping mechanisms among the 4 groups. Patterns of similarities and differences in mechanisms were identified. PMID- 1626332 TI - Inferred characteristics of successful suicides as function of gender and context. AB - This paper examines college students' attributions about suicide as a function of gender and context (athletic vs. relationship failure). Results indicated that male athletes who suicided were considered more emotionally well-adjusted compared to males who suicided because of a relationship failure and all females. Male and female athletes who suicided were seen as more competent and less distressed compared to those who suffered a failed relationship. Females were also seen as more distressed compared to males. These results are discussed in terms of a positive bias toward athletes in our society as well as gender stereotypes. Implications of these findings as well as methodological limitations are discussed. PMID- 1626333 TI - Sex-role change, anomie and female suicide: a test of alternative Durkheimian explanations. AB - Durkheim's influential book, Suicide, provides general (economic) anomie, conjugal anomie, and sex-role convergence explanations of changes in suicide rates under conditions of social change. We used trend analyses of American suicide rates and female/male suicide ratios from 1950 to 1984 and the regression of the ratios on female educational attainment, white female labor force participation, white fertility rates, and divorce rates to examine these explanations. The general anomie explanation of female suicide trends is supported for the middle-aged (30 to 54 years) but not for the young (10 to 30 years) or the elderly (55 to 74 years). The conjugal anomie proposition is at best supported for age groups between 15 and 44 when general anomie is not pronounced. The role convergence explanation is rejected for all 13 5-year-age groups. General anomie may not be a viable explanation of suicide trends for groups actively supporting relevant social changes or not yet tradition-bound or for groups whose retirement status reduces the importance of some social changes. PMID- 1626334 TI - Suicidal adolescents' perceptions of their family environment. AB - This study examined the extent to which adolescents' perceptions of their family environments were associated with suicidal behavior. Fifteen suicidal adolescents, 14 psychiatric controls, and 14 normal controls rated their families on cohesiveness, adaptability, parent-adolescent communication, parental caring, and parental over-protectiveness. Suicidal adolescents rated their families as the least cohesive and most rigid of the 3 groups, suggesting that adolescent suicidal behavior may occur when isolation is experienced within an inflexible family system. Suicidal and psychiatric control adolescents rated their families as similarly dysfunctional along the remaining variables, and as more dysfunctional than families of normal control adolescents. The implications of these findings are discussed, and it is suggested that several characteristics commonly attributed to families of suicidal adolescents may actually be general risk factors for adolescent psychopathology, rather than for suicidal behavior specifically. PMID- 1626335 TI - The impact of epidemic, war, prohibition and media on suicide: United States, 1910-1920. AB - The paper utilizes a natural experiment approach to estimate the impact of exogenous social and political events on suicide behavior in the United States between 1910 and 1920. The study is concerned with determining the impact of World War I, the great Influenza Epidemic, and the prohibition experiment on suicide. Estimating the monthly population in the United States registration area from 1910 to 1920, monthly suicide and mortality rates are computed. A time series model is postulated, and second-order autoregressive estimates are used to determine the impact of the independent variables in the model. It is concluded that World War I did not influence suicide; the Great Influenza Epidemic caused it to increase; and the continuing decline in alcohol consumption between 1910 and 1920 depressed national suicide rates. Further individual-level aggregate studies are needed to confirm the findings of the study. PMID- 1626336 TI - The effect of the media on suicide: the Great Depression. AB - Previous work on the media and suicide has neglected the mood of the audience in its models. The present study tests the thesis from symbolic interaction theory that the degree of media influence is contingent on audience receptivity. Audience receptivity to suicide stories is assumed to be high in the Great Depression given widespread unemployment, a condition thought to promote suicidogenic mood such as anomie. A taxonomy of stories is developed using classic imitation, social learning, and differential identification theories. Analysis of monthly data on suicide and publicized stories finds, however, little supporting evidence. Only stories concerning political leaders were associated with suicide. Stories concerning other categories of victims, such as villains, entertainers, and foreigners, were not associated with suicide. Possibly the potential impact was offset by other factors such as the absence of television to echo for the messages carried by the newspapers and radio and heightened political integration. PMID- 1626337 TI - Suicidal behavior and marital interaction. PMID- 1626338 TI - Characterization of thymic weight and thymic peptide thymosin-beta 4: effects of hypophysectomy, sex, and neonatal sexual differentiation. AB - An initial experiment was conducted to analyze the effects of hypophysectomy (Days 5-30 post hypophysectomy) on thymic weight and thymosin-beta 4 concentrations. After hypophysectomy, thymic weight and thymosin-beta 4 concentrations decreased with time (5, 10, 15, and 30 days post hypophysectomy) and by 30 days post hypophysectomy were reduced by 50%. Exp. II investigated the effects of early sexual differentiation on thymic weight and thymosin-beta 4 concentrations in pituitary intact and hypophysectomized male, female, nonmasculinized rats (via castration of males at Day 2 or 11 of age and androgenized female (at Day 3 of age) rats. Rats were hypophysectomized at 30 days of age and, at 17 days post hypophysectomy, the thymus gland was dissected and weighed. Serum was collected for thymosin-beta 4 analysis. At 47 days of age, males have a greater thymic weight when compared to females (p less than 0.01) but hypophysectomy eliminated any sex differences and significantly reduced thymic weights (p less than 0.05). Hypophysectomy did produce increased thymosin beta 4 concentrations across all treatments (p less than 0.01) and is considered to be a combination response of decreased gonadal function via lack of pituitary hormonal stimulation (luteinizing hormone and follicle stimulating hormone) and lack of gonadotrophic effects on the thymus gland and its secretory capacity. Hypophysectomized males and Day-2 castrate males had increased thymosin-beta 4 concentrations when compared to hypophysectomized females and neonatally androgenized females (p less than 0.05). Differences of thymic weights between male and female rats during prepubertal development are probably related more to presence or absence of gonads, gonadal steroids, and response of the thymus to pituitary secretagogues rather than to neonatal sexual differentiation of thymic function and secretion of thymosin-beta 4. PMID- 1626339 TI - Expression of a histone H1 gene (H1.1) in human testis and Hassall's corpuscles of the thymus. Expression of a histone H1 gene (H1.1). AB - The expression of a H1 gene (H1.1) was studied in several human tissues. Northern blot analysis revealed that this gene is expressed in testis and thymus, but not in other human tissues like liver, spleen, lung, brain, thyroid gland and skin fibroblasts. Furthermore in situ hybridization on tissue sections revealed a cell type specific expression of histone H1.1 gene in the Hassall's corpuscles of the thymus. PMID- 1626340 TI - How are the American Association of Blood Banks standards developed? PMID- 1626341 TI - Is it homologous or is it allogeneic? PMID- 1626342 TI - Detection of antibodies to human immunodeficiency virus type 2 (HIV-2) in blood donor sera using United States assay methods for anti-HIV type 1. AB - Twelve serum samples from French blood donors that were uniformly reactive in tests for antibody to human immunodeficiency virus type 2 (anti-HIV-2) also were reactive in 92 to 100 percent of tests with three anti-HIV type 1 (anti-HIV-1) enzyme-linked immunoassays currently in widespread use for donor screening in the United States. Supplemental tests for anti-HIV-1 on these anti-HIV-2-reactive samples differed in their responses. All samples reacted in a licensed anti-HIV-1 Western blot, but there was an atypical band near the p41 position, which could be a clue to the fact that this result was a cross-reaction with anti-HIV-2. A recombinant immunoblot gave an indeterminate result for anti-HIV-1 in all 12 samples. A local immunofluorescence assay for anti-HIV-1 reacted with 92 percent of the samples, but a commercial one detected only 58 percent. PMID- 1626343 TI - Ultraviolet-B irradiation of platelets: a preliminary trial of efficacy. AB - Prior studies established that ultraviolet-B light (UVB) irradiation of platelet concentrates (PCs) at appropriate doses can eliminate the mixed lymphocyte culture-stimulating and -responding capacity of lymphocytes in the PCs without adversely affecting in vitro platelet function. The in vivo recovery and survival and in vitro characteristics of UVB-irradiated platelets were investigated in paired studies. PCs were stored for 1 day and then exposed to UVB. Platelet recovery, survival, and function were comparable to those of nonirradiated platelets. Recovery and survival of platelets stored for 5 days before UVB exposure were decreased relative to controls, although they were considered clinically acceptable. Paired transfusion studies were also performed in seven thrombocytopenic patients by using platelets obtained by apheresis. Comparable posttransfusion platelet increments and bleeding time corrections were obtained with both irradiated and control (nonirradiated) platelets. It can be concluded that platelets survive and function relatively normally in vivo after UVB irradiation sufficient to abolish lymphocyte reactivity in mixed lymphocyte culture. Long-term studies of UVB-irradiated PCs are needed to assess their potential in reducing recipient alloimmunization. PMID- 1626344 TI - A comparison of two supplemental procedures for confirmation of antibody to hepatitis C virus c100-3 antigen in Louisiana blood donors. AB - In a pilot study designed to evaluate the performance of supplemental hepatitis C virus (HCV) tests, 146 consecutive HCV enzyme immunoassay (EIA)-reactive samples (0.98% of 14,949 donors) were comparatively evaluated with two sets of supplemental tests: HCV antibody neutralization/c100-3 peptide EIA and the first generation HCV recombinant immunoblot assay (RIBA). Of these samples, 68.5 percent were positive and 17.8 percent were negative on both supplemental assays. Nineteen samples were discordant. Eleven samples were positive on one assay (9 on neutralization/peptide, 2 on RIBA) and negative or indeterminate on the alternate supplemental test, but reacted with two additional HCV antigens outside the c100 3 region in a second-generation dot immunoblot assay. The dot immunoblot assay was used as a reference and reactive samples were considered confirmed. The remaining eight discordant samples were indeterminate or negative on either assay and did not react on the dot immunoblot assay. These data indicate a 0.74-percent prevalence of HCV exposure detected by reactivity with the c100-3 antigen in blood donors in southern Louisiana. PMID- 1626345 TI - Quantitation of red cell-bound IgG by an enzyme-linked antiglobulin test in human immunodeficiency virus-infected persons. AB - Anemia, thrombocytopenia, and neutropenia have been observed in patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex. To investigate whether red cells (RBCs) of patients with human immunodeficiency virus infection were coated with IgG and/or complement (C3), blood samples of 239 patients were tested. The prevalence of a positive direct antiglobulin test on RBCs was 16.7 percent. By use of an enzyme-linked antiglobulin test (ELAT) to measure more accurately the number of IgG molecules per RBC in a group of 67 patients, 30 of the 67 individuals were observed to have increased numbers (mean, 155) compared to normal controls and to patients with hypergammaglobulinemia due to multiple myeloma or chronic liver disease. Hemoglobin level was correlated with the number of IgG molecules per RBC (p = 0.008), but no correlation could be demonstrated between those numbers and serum immunoglobulin (p = 0.10) or circulating immune complexes (p = 0.38). Our results with ELAT suggest that some AIDS patients may have specific binding of IgG on the surface of their RBCs, rather than nonspecific uptake; further clinical correlations are necessary to confirm these findings. PMID- 1626346 TI - Storage of platelets in additive solutions: a new method for storage using sodium chloride solution. AB - The in vitro effect of 6-day storage of platelets prepared from 6 pooled buffy coat (BC) units and stored in a platelet storage medium containing approximately 40 percent CPD-plasma and 60 percent platelet additive solution (PAS) was evaluated. PAS is composed of sodium and potassium chloride, citrate, phosphate, and mannitol. The total count of platelets per pooled unit included in the in vitro studies (n = 25) was 376 +/- 59 x 10(9) (mean +/- SD). The present study included three steps. 1. Evaluation of platelet storage in one (n = 7) and two (n = 6) 1000-mL polyolefin containers using PAS. During storage in one container, significantly lower values were found for pH, pO2, glucose, ATP, and the ratio of ATP to AMP+ADP+ATP. The values for mean platelet volume, pCO2, lactate, and extracellular adenylate kinase activity were significantly higher. These results indicate that storage in only one polyolefin container is not appropriate for maintaining satisfactory platelet quality. During storage in two polyolefin containers, a remarkably decreased lactate production (0.07 +/- 0.02 mmol/day/10(11) platelets) was noted. 2. PAS was substituted for saline during 6 day storage in two 1000-mL polyolefin containers (n = 12). The composition of the platelet preparations was the same in all other respects. Similar in vitro results were noted with PAS and saline, which indicated that PAS has no specific effect on the storage of platelets different from that of saline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626347 TI - Preoperative red cell production in patients undergoing aggressive autologous blood phlebotomy with and without erythropoietin therapy. AB - Previous studies have demonstrated that autologous blood donors have a suboptimal endogenous erythropoietin response to the mild anemia induced by blood donation. Recent studies in baboons subjected to aggressive phlebotomy have shown an acceleration of erythropoiesis that may be beneficial perioperatively. To address the issue of accelerated erythropoiesis in autologous blood donors, red cell production during an aggressive preoperative autologous blood donation program was analyzed. The volume of red cells increased 568 mL (27% over baseline) and 911 mL (47% over baseline) for 23 placebo and 21 erythropoietin-treated patients, respectively, by hospital admission (9 days after last drug administration and 26 days after beginning therapy). The mean rate of additional red cell production was 22 mL per day in the placebo group and 34 mL per day in the erythropoietin group (p less than 0.001), which represents a twofold and a 2.5-fold increase over basal erythropoiesis, respectively. The major difference in red cell production in the placebo and erythropoietin groups occurred early in the collection period. It can be concluded that an aggressive autologous blood phlebotomy program results in clinically important increased erythropoiesis at the time of surgery. In patients unsuited for aggressive autologous phlebotomy, a more modest autologous blood procurement program, coupled with the administration of recombinant erythropoietin, may be a preferable approach. PMID- 1626348 TI - Effects of oral donor questioning about high-risk behaviors for human immunodeficiency virus infection. AB - The purposes of this study were 1) to compare blood donor deferrals resulting from additional, oral questions about human immunodeficiency virus risk behaviors with deferrals resulting from currently used, written screening questions; 2) to examine differences in donor deferral resulting from use of an indirect (IQ) versus direct (DQ) additional oral question format; and 3) to evaluate written survey responses of donors and staff members to the additional questions. The IQ group (n = 3050) were asked if they understood the seven ineligible-donor risk behaviors, and the DQ group (n = 4753) were asked if they had engaged in any of these behaviors. Owing to positive answers or refusal to answer the additional questions, there was an increase in donor deferrals, over the level seen with customary screening. Only 1 percent of donors indicated they would not return if the questions were asked in the future. Embarrassment was indicated by 3 percent of the IQ group and 7 percent of the DQ group; 14 to 15 percent preferred to write their answers rather than give them orally. The staff members generally felt training was adequate (IQ = 92%, DQ = 83%) and were comfortable asking the questions (IQ = 82%, DQ = 78%). Mean screening times were 5.7 minutes before the addition of the oral questions, 7.5 minutes with IQ, and 7.6 minutes with DQ. This study confirms the value of IQ and DQ formats in identifying potentially infectious donors and suggests that the DQ format may be slightly more effective. PMID- 1626349 TI - Electronmicroscopic examination of white cell reduction by four white cell reduction filters. AB - The mechanisms of white cell (WBC) reduction in 16-hour-old CPDA-1 red cell (RBC) concentrates by filtration on a column filter and on three different flatbed filters were studied by electron microscopy, with special emphasis on cell-to cell interaction, cell damage, and interaction of blood cells with the material. Generally, lymphocytes were removed by mechanical sieving and monocytes by adherence and mechanical sieving. Granulocyte depletion occurred by mechanical sieving, direct adhesion to the fibers, and indirect adhesion to activated and spread platelets. In the column filter, most granulocytes were captured by adhesion. In the coarse layers of two of the flatbed filters, indirect adhesion was most prominent, whereas direct adhesion was most prominent in the other flatbed filter. For the most part, granulocytes were captured by direct adhesion in the fine layers, but in one flatbed filter, capture apparently occurred by mechanical sieving. The results of this study suggest that the efficiency and the mechanism of WBC reduction depend on the physicochemical characteristics of the non-woven materials in the filters as well as the cellular composition of the RBC concentrates. PMID- 1626350 TI - Red cell transfusions in coronary artery bypass surgery (DRGs 106 and 107) AB - To study red cell transfusion practice in 3216 coronary artery bypass graft (CABG) cases in 11 hospitals in 1988, abstracted patient records were stratified by diagnosis related group (DRG) (that is, DRG 106, coronary artery bypass without catheterization, or DRG 107, coronary artery bypass with catheterization) and International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) surgical procedure code. Means of units per transfused patient, age and length of stay, and in-hospital mortality rates were significantly greater for patients in DRG 106 than DRG 107. Gender was a significant factor for transfusion outcomes; female patients were more likely to undergo transfusion, and, when transfused, they received more units of red cells than male patients. For a given DRG/ICD-9-CM surgical procedure class, significant differences were found between hospitals in the percentage of patients transfused, but not in mean units of red cells per transfused patient. However, within individual hospitals, the proportion of patients transfused and the number of units per transfused patient did not vary significantly across DRG/ICD-9-CM procedure classes. These results suggest that circumstances operating within a hospital, still to be identified, had more influence on transfusion decisions than the nature of the surgical intervention. PMID- 1626351 TI - Duties to donors. PMID- 1626352 TI - Molecular biology of red cell blood group genes. AB - The explosion of new information and technology for probing the fine architecture of gene structure has already brought new insights into the varied phenotypic expression of red cell blood group antigens. Molecular biologic techniques will be increasingly applied to red cell antigens as well as blood group antigens on other blood cells. Not since the introduction of the Coombs reagent has such a powerful method been available with which to increase our understanding of the nature of blood cell antigens. PMID- 1626353 TI - What is a blood group antigen? PMID- 1626354 TI - Is it homologous or allogeneic? PMID- 1626355 TI - A review of the usefulness of myelography in 50 dogs. AB - Fifty dogs showing clinical signs of spinal disease were investigated by myelography, using iopamidol. In 27 cases the technique was considered worthwhile. Of the 19 dogs not subjected to surgery or euthanasia as a result of the findings, three suffered seizures during recovery from anaesthesia, eight deteriorated in neurological condition and one suffered permanent respiratory arrest as a result of extensive subarachnoid haemorrhage. PMID- 1626356 TI - Staphylococci on the skin of pigs: isolates from two farms with different antibiotic policies. AB - Staphylococci isolated from pigs on two farms were identified and their antibiotic resistance and plasmid profiles were examined. A highly resistant Staphylococcus hyicus was epidemic on one of the farms which was also that at which antibiotic-containing feedstuffs were used most often. Staphylococci from this farm were more often resistant to two or more antibiotics than were the strains from the other farm. The many plasmids present in these staphylococci prevented the determination of the genetic nature of the antibiotic resistance. PMID- 1626357 TI - Abomasal dilatation and impaction in two Hampshire rams. AB - Two adult Hampshire rams, unrelated and from separate farms, were examined for the cause of intermittent bloat and, or anorexia which lasted for three to six weeks and caused depression and cachexia. The rumen of each ram was hypermotile and ballottement of the ventral abdomen of each animal revealed an enlarged doughy viscus. Mild prerenal azotaemia, hypokalaemia with metabolic alkalosis, and high rumen chloride concentrations were evident. One ram died during the induction of anaesthesia for an abomasotomy and the other was euthanased after unsuccessful medical therapy. The abomasum of each ram was four to six times larger than that of a normal adult ram and filled with coarse, semi-moist, impacted ingesta. This abnormality was clinically identical to the abomasal emptying syndrome which has been described only in the Suffolk breed. PMID- 1626358 TI - Successful use of a QT-sensing rate-adaptive pacemaker in a dog. PMID- 1626359 TI - Availability of medicines. PMID- 1626360 TI - Transmission of blue-eared pig disease. PMID- 1626361 TI - Acral lick dermatitis in a dairy cow. PMID- 1626362 TI - Dangerous dogs. PMID- 1626363 TI - Disease hazards for UK livestock. PMID- 1626364 TI - Oxalate urolithiasis in Dandie Dinmont terriers. PMID- 1626365 TI - A competitive ELISA using anti-N monoclonal antibodies for specific detection of rinderpest antibodies in cattle and small ruminants. AB - A competitive ELISA (C-ELISA) using monoclonal antibodies (mAbs) which bind to the nucleo-protein (NP) of rinderpest virus (RPV) for detection of RPV antibodies in cattle and small ruminant sera is described. Unlike virus neutralisation test (VNT), this test using mAb IVB2-4, can detect specific RPV antibodies without showing a cross-reaction with antibodies to peste-des-petits ruminants-virus (PPRV); by contrast, when mAb VE4-1 is used the test detects both RPV and PPRV antibodies, including low levels of antibodies that can be found in sera containing maternal antibodies. Although antibodies to the PPRV 75-1 strain are also detected with mAb 51-5-6, the test is suitable for assessing the immune status of cattle against the Rinderpest Old Kabete (RBOK) strain. The results from a panel of sera with a known status of vaccination provide evidence for a highly significant correlation between C-ELISA and VNT. This test may be a useful tool for a standardized and accurate determination of the immunity status of both cattle and small ruminants. PMID- 1626366 TI - Characterisation and biological activity of monoclonal antibodies specific for Pasteurella haemolytica A1 capsule and lipopolysaccharide. AB - Monoclonal antibodies (mAb) against both Pasteurella haemolytica A1 capsule and lipopolysaccharide (LPS) were produced. Anti-capsule mAb reacted with the homologous A1 serotype only, whereas mAb against LPS reacted with P. haemolytica serotypes A2, A5, A8, A12, A14 and A16 but not with 33 bacterial species or rough LPS mutant strains tested. Both capsule and LPS antigens were visualised on the surface of bacteria by immunogold electron microscopy. Neither of the mAbs demonstrated antibody-dependent complement-mediated killing in vitro but both facilitated phagocytosis in vitro. PMID- 1626367 TI - Serological assay for swine erysipelas using nitrocellulose particles impregnated with an immunodominant 65 kDa antigen from Erysipelothrix rhusiopathiae. AB - Pigs (n = 10) that were experimentally challenged with an arthritogenic isolate of Erysipelothrix rhusiopathiae (strain VRS 229; serotype 1a) developed arthritis in at least one of twelve major limb joints. Immunoblots using sera obtained from these pigs at necropsy revealed a major band of immunoreactivity against a subunit polypeptide of apparent molecular mass 65 kDa. The usefulness of the 65 kDa immunodominant subunit as an assay reagent in an ELISA test was examined by presentation of antigen impregnated onto nitrocellulose particles (AINP). This was prepared by electro-transfer of bacterial polypeptides from SDS-PAGE gels to nitrocellulose. Protein bands were visualized by staining with amido black and a strip of nitrocellulose bearing the 65 kDa band was excised and extracted with formic acid. Nitrocellulose particles impregnated with the 65 kDa antigen (65 AINP) were precipitated from solution by neutralization with ammonium hydroxide. 65-AINP was suspended in water and the optimum dilution for ELISA assay was determined by titration to be 0.1 A650 units. Sera from all pigs challenged with VRS 229 reacted against the 65-AINP antigen in the ELISA assay while sera from control, and experimental pigs prior to challenge, failed to do so. The 65-AINP antigen could also be used efficaciously to quantify serological reactivity of pigs experimentally infected with other strains of E. rhusiopathiae representing the three major serotypes (1a, 1b and 2) that are most commonly associated with swine erysipelas infections. Mouse immunizations with 65-AINP also confirmed that nitrocellulose particles bearing the immunodominant subunit antigen will elicit murine antibodies that are monospecific against this determinant. PMID- 1626368 TI - Species identification and some characteristics of coagulase-negative staphylococci isolated from bovine udders. AB - The species of 203 strains of coagulase-negative staphylococci (CNS), isolated from bovine udder quarters was determined; all were tested for hydrophobicity and encapsulation, attributes that may relate to virulence. Twelve species were identified, of which Staphylococcus simulans, (34.5%), S. chromogenes (16.7%), S. epidermidis (13.8%) and S. xylosus (8.9%) were the most frequent. The majority of strains possessed a hydrophilic cell surface. However, strains from two species (S. chromogenes and S. epidermidis) were more hydrophobic than the others. Only five strains were encapsulated (S. xylosus, 3; S. saprophyticus, 1; and S. sciuri, 1). Judging from the low frequencies of hydrophobic and encapsulated strains, and comparing with strains isolated from clinical cases, it is suggested that these properties are not major virulence determinants of CNS. PMID- 1626369 TI - Cross protection studies on Bordetella bronchiseptica in mice using an intracerebral challenge model. AB - Protective activities of heat-inactivated (60 degrees C for 30 min) merthiolate preserved Bordetella bronchiseptica and B. pertussis bacterins were compared in intraperitoneally immunized mice challenged intracerebrally (i.p./i.c.) or intraperitoneally (i.p./i.p.). In the i.p./i.c. assay (Kendrick test), a B. pertussis bacterin protected mice against challenge with B. pertussis 18-323, as well as against phase I cytotoxic and non-cytotoxic strains of B. bronchiseptica. A B. bronchiseptica bacterin, prepared from a phase I cytotoxic strain, gave protection against two phase I B. bronchiseptica strains, irrespective of their cytotoxin-production. A non-cytotoxic phase I strain of B. bronchiseptica elicited protection against the homologous strain only. Neither cytotoxic nor non cytotoxic B. bronchiseptica strains protected mice challenged with B. pertussis 18-323. Vaccines prepared from phase III strains of B. bronchiseptica were not protective at all against any of the challenge strains. No such differences in the protective activities of the bacterins could be detected by the i.p./i.p. method. They seem to cross-protect equally well. The results indicate that the Kendrick test may be useful in testing potency of different B. bronchiseptica bacterins. PMID- 1626370 TI - The effect of exposure to a delta cya/delta crp mutant of Salmonella typhimurium on the subsequent colonization of swine by the wild-type parent strain. AB - This study characterizes the clinical response and colonization pattern of caesarean-derived, colostrum-deprived swine exposed to a delta cya/delta crp mutant (chi 4233) of S. typhimurium and challenged with the wild-type parent strain. chi 4233 was mildly virulent in swine and induced transient fever and soft stools. Chi 4233 colonized the ileum, cecum, liver, spleen, tonsils, and mandibular and ileocolic lymph nodes of swine in a manner similar to the parental wild-type, but the numbers of S. typhimurium (chi 4233) in the ileum were 100- to 1000-fold less than those of pigs exposed to the parental wild-type. Pigs exposed to chi 4233 21 days before parental wild-type challenge demonstrated a milder clinical response to challenge than did pigs that did not receive chi 4233. The wild-type populations in the ilea of chi 4233-exposed pigs after challenge were 100- to 10,000-fold less than those in pigs not receiving chi 4233. The liver, spleen, and ileocolic lymph nodes were cleared of wild-type S. typhimurium more quickly after challenge in chi 4233-exposed pigs. The populations of chi 4233 in the ilea of exposed pigs after wild-type challenge were also less than would have been expected in unchallenged pigs. Thus, exposure of swine to a delta cya/delta crp mutant of S. typhimurium modulated the subsequent response to parental wild type challenge and reduced carrier populations of wild-type S. typhimurium in infected swine. PMID- 1626371 TI - The pathogenesis of edema disease in pigs. A review. AB - Edema disease is known to cause important losses in the period shortly after weaning. Although the disease is known for many decades, intensive studies with bacterial lysates of pathogenic E. coli, followed by biotechnological research the last ten years, has led to a better understanding of its pathogenesis. Especially the impact of the toxin is clearly established. Evidence also exists that adhesion factors play a crucial role in the pathogenesis of edema disease. PMID- 1626372 TI - Tissues and exudates contain sufficient thymidine for growth of anaerobic bacteria in the presence of inhibitory levels of trimethoprim-sulfamethoxazole. AB - Obligate anaerobes are susceptible in vitro to trimethoprim-sulfonamides. Clinical efficacy of this drug combination for treatment of infectious processes in which anaerobes are involved is uncertain. We hypothesize that this uncertainty is a result of thymidine in tissues and exudates which abrogates the inhibitory effect of trimethoprim-sulfonamides. We shown herein that species of anaerobic bacteria commonly encountered in infectious processes grew on thymidine containing medium despite the presence of levels of trimethoprim-sulfamethoxazole (S x T) previously shown to be inhibitory. Biologic fluids and tissues, where anaerobic bacteria are commonly encountered in diseased states, were shown to contain thymidine levels that were sufficient to reverse the inhibitory effect of S x T upon these species of bacteria. These observations suggest that the use of trimethoprim-sulfonamides is not a rational choice for treatment of infectious processes in which an obligate anaerobe is a component. PMID- 1626373 TI - ELISA tests for antibodies in experimental bovine tuberculosis. AB - It was shown that 10(4) cfu of a field isolate of Mycobacterium bovis caused illness in five experimentally infected calves; one of these died. One of three contact calves also became clinically infected. Considerable variation in the humoral response of the affected animals was demonstrated by ELISAs using purified protein derivative (PPD) and phosphatide antigens. The inoculation of antigens used in the comparative tuberculin skin test significantly enhanced the level of PPD antibodies in the affected animals whereas that of the apparently non-infected contact animals remained unchanged. PMID- 1626375 TI - Restriction endonuclease analysis of DNA from ruminant Chlamydia psittaci and its relation to mouse virulence. AB - DNA from 20 pathogenic or non-pathogenic ruminant strains of Chlamydia psittaci was compared by restriction endonuclease analysis. The strains could be easily differentiated according to their invasiveness for mouse, whatever their pathological origin. DNA patterns of invasive strains were similar, whereas those of non-invasive strains were distributed in two groups. PMID- 1626374 TI - Detection of entero- and verocyto-toxin genes in Escherichia coli from diarrhoeal disease in animals using the polymerase chain reaction. AB - Oligonucleotide primers were designed for the specific polymerase chain reaction (PCR) amplification of the enterotoxins STIa and LTI and of the verocytotoxins VT1 and VT2. All of 184 E. coli isolates from cases of diarrhoea from pigs, cattle and sheep gave identical toxin profiles by PCR and gene probe. Differentiation between VT2 and VT2v was achieved using two oligonucleotide primers pairs in PCR and showed that all of 34 VT2+ porcine isolates, of which 23 were 0138:K1, harboured VT2v whereas 20 VT2+ bovine and ovine isolates harboured VT2. No isolate harboured both VT2 polymorphs. Simplified methods for sample preparation for PCR were examined and showed that PCR was not inhibited by direct addition of broth culture to the reaction mixture. PMID- 1626376 TI - Typing of Australian isolates of Treponema hyodysenteriae by serology and by DNA restriction endonuclease analysis. AB - A total of 91 isolates of Treponema hyodysenteriae which were obtained from 62 piggeries located around Australia were typed by serology and by DNA restriction endonuclease analysis (REA). The isolates fell into eight serogroups, of which groups B and D were the most common. Isolates with different REA patterns were recognised within serogroups, whilst a few isolates with the same REA pattern were placed into different serogroups. Some of the latter isolates were either from the same piggery or from farms with epidemiological links, thus indicating the bacteria may have altered their antigenic properties. A total of 31 different REA patterns were recognised amongst the Australian isolates. These comprised eight major patterns, with four of these being subdivided on the basis of minor differences in banding. Where a number of isolates were obtained from individual piggeries these all had the same REA pattern, and in one piggery isolates with the same pattern were recovered over a five year period. Plasmid bands were observed in 70 of the Australian isolates (77%), and in six of the seven overseas isolates included in the study for comparison. These plasmids did not affect the REA pattern. Of the States from which substantial numbers of isolates were examined, the greatest number of different strains (12 amongst 19 piggeries) were found from Victoria, and there were 10 REA patterns in strains from 24 piggeries in Queensland. Despite the large total number of different strains of T. hyodysenteriae in Australia, only three were found in more than one State. PMID- 1626377 TI - Chromosomal DNA probes for the identification of asaccharolytic anaerobic pigmented bacterial rods from the oral cavity of cats. AB - A dot-blot hybridisation assay using isolated high molecular weight DNA as whole chromosomal probes of the cat pigmented asaccharolytic Bacteroides/Porphyromonas species was used against both purified high molecular weight DNA and DNA released on membranes from whole cells for the identification of B. salivosus and for its differentiation from the other anaerobic species isolated from normal and diseased mouths of cats and horses. 32P-labelled probes were compared with digoxigenin (DIG)-labelled probes (Boehringer-Mannheim). The whole chromosomal probes were specific--differentiating B. salivosus from a variety of species (including members of the genera Bacteroides, Fusobacterium, Eubacterium, and Prevotella) found in normal and abnormal mouths of cats and horses. Likewise, asaccharolytic black pigmented Group 2 strains were distinguishable from all strains tested. However, cat strains of P. gingivalis which show 68-76% DNA-DNA homology with human strain P. gingivalis ATCC 33277T, were not distinguishable from each other using either 32P-labelled or DIG-labelled probes. The minimum amount of pure Bacteroides DNA which could be detected by the 32P-labelled probe was 100-300 pg, while the amount of pure DNA detected by the DIG system was 1-3 mg after room temperature colour development for 1 h and 100-300 pg after 6 h colour development. PMID- 1626378 TI - Different stabilities to bile among feline calicivirus strains of respiratory and enteric origin. AB - Feline calicivirus (FCV) strains isolated from feces (E-FCV) were compared with FCV strains of respiratory origin (R-FCV). All strains were shown to be labile at pH 3.0. All strains except one strain of E-FCV were found to be sensitive to the action of trypsin. When exposed to bile salt (deoxycholic acid sodium salt), all R-FCV strains were markedly inactivated, but none of the E-FCV strains was inactivated. It was possible to select bile-resistant substrains from a bile sensitive strain. PMID- 1626379 TI - Effects of four preparations of 0.05% chlorhexidine diacetate on wound healing in dogs. AB - Four chlorhexidine diacetate (CHD) antiseptic wound lavage preparations were evaluated in vivo to determine their effects on second intention wound healing in the dog in vitro to determine their relative antibacterial activity against Staphylococcus intermedius. Chlorhexidine was diluted to 0.05% in sterile water, 0.9% sodium chloride, lactated Ringers solution (LRS), and LRS that was allowed to form a precipitate with CHD. Control solutions included sterile water and LRS. There were no significant differences in wound contraction or epithelialization. All 0.05% CHD preparations provided 100% bacterial kill. PMID- 1626380 TI - Effects of flunixin meglumine on dogs with experimental gastric dilatation volvulus. AB - Gastric dilatation-volvulus (GDV) was created experimentally and maintained for 90 minutes in 16 anesthetized, mixed-breed dogs. After the GDV was corrected, normal saline solution (0.044 mL/kg intravenously [IV]) was administered to eight dogs (controls), and flunixin meglumine (2.2 mg/kg IV) was administered to eight dogs. Microspheres labeled with radioactive cobalt, scandium, tin, or niobium were injected intravenously at baseline (before GDV) and minutes 90, 100, and 270, respectively, to determine tissue blood flows. Plasma endotoxin and prostacyclin were measured at the same intervals. Electrocardiogram, mean arterial pressure, portal pressure, and cardiac output were recorded continuously. Dogs were euthanatized at minute 270 and necropsied. There was no significant difference between treatment groups for any measured variable at any time. Endotoxin levels increased significantly during GDV. Prostacyclin levels were lower in dogs treated with flunixin meglumine than in controls at minutes 210 and 270. Histopathologic findings were similar for all dogs and consistent with those associated with endotoxemia. Flunixin meglumine treatment did not alter cardiac indices or tissue blood flows significantly. However, elevation of prostacyclin was inhibited by flunixin meglumine, which suggested that continued effects of endotoxic damage might be attenuated or inhibited. PMID- 1626381 TI - Suspensory apparatus prosthesis in the horse. Part 1: In vitro mechanical properties. AB - Mechanical properties of equine suspensory apparatus preparations and three braided synthetic prostheses were evaluated in vitro. Force versus displacement plots and failure modes were recorded from single load-to-failure testing in 18 cadaver limbs before and after replacement of each suspensory apparatus with a prosthesis. Mean load at failure, energy to failure, and stiffness values of polytetrafluoroethylene (PTFE) prostheses were lower than those of the suspensory apparatus and aramid prosthesis. The PTFE prosthesis failed by elongation or rupture of the prosthesis. Mechanical properties of the aramid prosthesis with collar augmentation were not significantly different from the suspensory apparatus. The main site of failure in both aramid prostheses was at the screw fixation to bone. PMID- 1626382 TI - Suspensory apparatus prosthesis in the horse. Part 2: In vivo evaluation in a suspensory apparatus disruption model. AB - The suspensory apparatus of one forelimb was surgically disrupted in six adult horses by transecting the distal sesamoidean ligaments. A double-braided prosthetic ligament made of aramid yarn was installed to support the flexor surface of the metacarpophalangeal joint. The prosthesis was routed through tunnels in the third metacarpal bone and proximal phalanx, and secured to bone with screws. Evaluation by radiography, synovial fluid analysis, cinematography, and dynamography was performed before surgery and at weeks 16 and 30. Supracondylar cortical lysis and periosteal proliferation were observed on postoperative radiographs. Synovitis and fragmentation of the prosthesis were apparent from synovial fluid evaluation. Weight bearing and metacarpophalangeal joint motion were decreased and loading was transferred in part to the opposite forelimb. Clinical lameness improved and weight bearing increased during the second half of the 30-week period. At necropsy, there was abrasion of the prosthesis and the articular surfaces in contact with the prosthesis. Diffuse granulomatous synovitis developed in response to aramid fiber fragments within the synovium. PMID- 1626383 TI - Corticocancellous bone biopsy from the 12th rib of standing horses. AB - Unicortical corticocancellous bone biopsy specimens 4.5 mm and 6.5 mm in diameter were obtained without long-term complications from the 12th rib in eight standing horses. However, the bone specimens were unsuitable for histologic or histomorphometric evaluation. In in vitro comparisons of biopsy specimens 6.5 mm and 12 mm in diameter, and of unicortical and transcortical biopsy specimens, 12 mm transcortical specimens yielded the most cancellous bone. Transcortical bone biopsy specimens 12 mm in diameter were obtained from eight horses by using power assisted trephination. The surgical procedure was well tolerated, but some degree of pneumothorax in all horses was treated by aspiration of air from the thorax. Long-term complications were not observed. PMID- 1626384 TI - Arthrographic analysis of communication between the tarsometatarsal and distal intertarsal joints of the horse. AB - The intra-articular anatomy of 103 equine tarsi was studied by contrast radiography with image intensification and computerized tomography. There was communication between the tarsometatarsal and distal intertarsal joints in 21 of 55 (38%) interpretable tarsometatarsal arthrograms, and in 11 of 48 (23%) interpretable distal intertarsal arthrograms. The difference was not significant. The volume of contrast agent and the pressure of injection did not correlate with communication. Forced injection caused subcutaneous leakage of contrast medium but not communication. Communication occurred via the tarsal canal and the space between the third and the combined first and second tarsal bones. Injection of the distal intertarsal joint from the dorsomedial aspect of the limb, distal to the palpable distal border of the medial branch of the tendon of the tibialis cranialis muscle and between the central, third, and combined first and second tarsal bones, provided reliable access except in the presence of severe periosteal proliferations. PMID- 1626385 TI - Long-term outcome of tooth repulsion in horses. A retrospective study of 61 cases. AB - The records of 61 horses undergoing tooth repulsion for treatment of alveolar periostitis were reviewed. Seventeen of 36 horses (47%) in which maxillary teeth were removed had serious postoperative complications, such as infection of a second tooth, bone sequestration, chronic sinusitis, draining tracts, retained dental packing, feed impaction of the alveolus or sinus, suture-line dehiscence, or skin-flap sloughs. Eight horses required at least one additional surgical procedure. Eight of 25 horses (32%) in which mandibular teeth were removed had serious postoperative complications, and four horses required an additional surgical procedure. Hospitalization lasted 2 to 61 days (median, 22 days) for maxillary teeth and 3 to 35 days (median, 8 days) for mandibular teeth. Long-term follow-up (at least 5 months) was possible in 47 horses. Twenty-four of 30 horses (80%) with maxillary tooth repulsion healed without further problems; six horses had persistent nasal discharge. Fourteen of 17 horses (82%) with mandibular tooth repulsion healed with no further problems or with only minor complications; three horses had a chronic draining tract. PMID- 1626386 TI - Levator nasolabialis muscle transposition to prevent an orosinus fistula after tooth extraction in horses. AB - The ventral part of the levator nasolabialis muscle was transposed to the alveolar defect after sinusotomy and tooth extraction in five normal horses and six horses with a tooth root abscess and sinusitis. In the normal horses at weeks 6, 10, 14 and 18, the transposed muscles remained viable and were incorporated into the recipient sites, and orosinus fistulae did not form. Histologically, there was a progressive transition from muscle to fibrous tissue. There was no facial deformity or loss of nasal function at the donor site. A localized abscess was associated with incomplete removal of tooth root fragments in one horse. After 1 year or more, five horses treated for dental disease had complete resolution of clinical signs. One horse continued to have intermittent mild nasal discharge. PMID- 1626387 TI - Trigger points in 48 dogs with myofascial pain syndromes. PMID- 1626388 TI - Radiographic criteria for evaluation of uncemented total hip replacement in dogs. AB - A zonal analysis system and corresponding nomenclature were developed to describe the location and nature of radiographic changes in canine uncemented total hip arthroplasties. Criteria to assess prosthetic component alignment, percentage of femoral canal fill, resorptive and formative bony changes, and alterations in the bone at the implant-bone interface were derived by studying serial radiographs of 100 consecutive canine uncemented total hip arthroplasties for up to 30 months after surgery. PMID- 1626389 TI - Mechanical evaluation of three methods of plating distal radial osteotomies. AB - Eighteen intact canine cadaver radii underwent nondestructive axial testing, and were osteotomized, plated, and retested. Each bone was tested with and without mediolateral or craniocaudal restriction of motion. Fixation of the osteotomies was performed under static compression with a cranially applied 5-hole 3.5 mm dynamic compression plate, a cranially applied 7-hole 3.5 mm T-plate, or a medially applied 7-hole 2.7 mm dynamic compression plate. There was no loss of axial stiffness after osteotomy and fixation, and there were no differences in axial stiffness between the methods of fixation. Mediolateral stiffness (bending around the craniocaudal axis) was consistently greater than craniocaudal stiffness (bending around the mediolateral axis) before and after osteotomy and plate fixation. There was no difference in the axial stiffness of otherwise intact radii when craniocaudal or mediolateral screw holes were drilled; however, all radii with craniocaudal screw holes and one radius with mediolateral screw holes fractured at a screw hole at high axial loads. PMID- 1626390 TI - Implantation of an uncemented total hip prosthesis. Technique and initial results of 100 arthroplasties. AB - A porous-coated modular total hip system was developed for uncemented implantation in dogs. The operative technique was developed in cadaver bones and live animals. One hundred uncemented total hip arthroplasties were performed in 92 dogs. Results were successful in 98% of the joints during follow-ups of 3 months or more. Complications included three luxations of the prosthetic joint, two fissure fractures of the femoral cortex, and one complete displacement of the acetabular component from its bony bed. Four complications were resolved successfully. PMID- 1626391 TI - Mechanical evaluation of half-pin (type 1) external skeletal fixation in combination with a single intramedullary pin. AB - Half-pin (type 1) external skeletal fixators with four, three, and two fixation pins and an intramedullary pin, and four-pin external skeletal fixators without an intramedullary pin were applied to prepared canine femurs. Load to failure, load to yield, safe load, and stiffness under compressive and torsional loads were calculated. When tested in compression, all measurements for the four-pin fixators with an intramedullary pin were significantly higher than for the two pin fixators with an intramedullary pin. The values for all parameters except load to yield were significantly higher for the four-pin fixators with an intramedullary pin than for the four-pin fixators without an intramedullary pin. When tested in torsion, all measurements for the four-pin fixators with an intramedullary pin were significantly higher than for the two or three-pin fixators with an intramedullary pin. PMID- 1626392 TI - Partial or total hemipelvectomy in the management of sarcomas in nine dogs and two cats. AB - The functional results of partial or total hemipelvectomy in seven dogs and two cats with sarcomas involving the pelvis were excellent, and the cosmetic outcome was acceptable to all owners. Tumors in two dogs were inoperable. Locally recurrent cancer occurred in two animals and metastases occurred in three animals. Three dogs survived longer than 2.5 years and the overall and disease free survival at 12 months was 62%. It appears that osteosarcoma of the pelvis is at least as aggressive as osteosarcoma of limbs and, unless effective adjuvant therapy is used, poorer survival results are likely in dogs with osteosarcoma than with other sarcomas of the pelvis. Hemipelvectomy is an aggressive surgical procedure that can be used successfully in selected dogs and cats with cancer involving the pelvis. PMID- 1626393 TI - Effects of arytenoid abduction and modified castellated laryngofissure on the rima glottidis in canine cadavers. AB - The percentages of change in cross-sectional area and dorsoventral height of the rima glottidis were measured after seven types of laryngoplasty in 30 postmortem canine specimens. The mean increases in area after each procedure were, in decreasing order, bilateral cricoarytenoid disarticulation with interarytenoid sesamoid band transection before placement of arytenoid abduction sutures 350% +/ 42%, bilateral placement of arytenoid abduction sutures 318% +/- 40%, bilateral cricothyroid disarticulation before placement of arytenoid abduction sutures 255% +/- 51%, modified castellated laryngofissure 244% +/- 30%, unilateral cricoarytenoid disarticulation with interarytenoid sesamoid band transection before placement of an arytenoid abduction suture 161% +/- 25%, unilateral placement of an arytenoid abduction suture 151% +/- 24% and unilateral cricothyroid disarticulation before placement of an arytenoid abduction suture 108% +/- 25%. Bilateral cricoarytenoid disarticulation with interarytenoid sesamoid band transection before placement of arytenoid abduction sutures resulted in a significantly greater increase in rima glottidis area than modified castellated laryngofissure and all unilateral arytenoid abduction techniques. Modified castellated laryngofissure resulted in a significantly greater increase than unilateral placement of an arytenoid abduction suture and cricothyroid disarticulation before placement of an arytenoid abduction suture. Bilateral disarticulation of the cricothyroid joint before placement of arytenoid abduction sutures resulted in significant collapse of the dorsoventral height of the rima glottidis. PMID- 1626394 TI - En bloc resection of primary rib tumors in 40 dogs. AB - Single or multiple rib resection was performed in 40 dogs for the treatment of primary osteosarcoma or chondrosarcoma. The resulting thoracic wall defect was closed with polypropylene (12 dogs), primary muscle flap (16 dogs), diaphragmatic advancement (10 dogs), or a combination (2 dogs). Few immediate (less than 2 weeks) postoperative complications were observed. Twenty dogs with osteosarcoma had a median survival time of 3.3 months (range, 0.5 to 23 months), with a 20% 6 month survival time. Metastases occurred in all the dogs. Fourteen dogs with chondrosarcoma followed up longer than 2 weeks had a median survival time of 10.7 months (range, 0.5 to 36 months) with a 64% 6-month survival time. Eight dogs developed metastases, five died from concurrent disease, and one dog is alive. Dogs with chondrosarcoma survived significantly longer than dogs with osteosarcoma. Survival time was not related to tumor size or number of ribs resected. PMID- 1626395 TI - Pleural compartmentalization in a dog with a pleuroperitoneal shunt. AB - Four years after successful implantation of a pleuroperitoneal shunt in a dog with persistent pleural effusion, signs of lethargy and dyspnea reappeared. Although the shunt was still functional, compartmentalization of the right pleural space eventually isolated a pocket of fluid, causing dyspnea. Symptomatic relief was achieved for at least 11 months by contralateral implantation of a second shunt. PMID- 1626396 TI - Continent jejunal reservoir (Kock pouch) for urinary diversion in dogs. AB - Urinary diversion by transplantation of both ureters into a reservoir constructed from 60 cm of jejunum was performed in six clinically normal dogs. The reservoir was connected to a stoma on the abdominal wall through a valve constructed from a short segment of intussuscepted bowel to provide continence. The reservoir was emptied three times daily by catheterization. One dog did not survive the surgical procedure and two dogs died within 1 week of surgical complications. The postoperative capacity of the reservoir in surviving dogs was 100 to 200 mL; it increased during the first month to 600 to 750 mL. Continence was excellent in two dogs. One dog was continent until month 2, when partial slippage of the intussusception occurred. A reversible hyponatremic, hypochloremic, hypokalemic metabolic acidosis developed. Bacteriuria was not responsive to systemic or local instillation of antibiotics. Ascending pyelonephritis, hydroureter, and hydronephrosis occurred in two dogs. Struvite urinary calculi formed in one dog. The procedure as described would be unsuitable for clinical use in dogs. PMID- 1626397 TI - Short-bowel syndrome in four dogs. AB - Short bowel syndrome occurred in four dogs after extensive (74% to 88%) small intestinal resection. Weight loss and diarrhea were the principal clinical signs. Treatment was based on the severity of clinical signs. One dog is alive after 27 months. Three dogs died within 3 months. The prognosis depends on the extent and site of resection, degree of intestinal adaptation, preoperative condition, and postoperative care. PMID- 1626398 TI - The effect of tension on perfusion of axial and random pattern flaps in foals. AB - Caudally based axial pattern and random pattern skin flaps, 5 cm x 10 cm, were raised on the abdomens of seven foals. Blood flow was measured 7.5 cm from the flap bases during incremental increases in applied tension. At tensions less than 1400 g, cutaneous blood flow was more than four times higher in axial pattern flaps than in random pattern flaps. Blood flow in axial pattern flaps at tensions up to 1500 g was greater than baseline flow in random pattern flaps. After removal of applied tension, perfusion in axial pattern flaps gradually increased but remained below baseline values. A short period of hyperperfusion after removal of tension in random pattern flaps may have been indicative of accumulation of waste products and localized acidosis. All flaps healed in their donor beds without complications. PMID- 1626399 TI - Arthrodesis for congenital flexural deformity of the metacarpophalangeal and metatarsophalangeal joints. AB - A llama, a miniature horse, and a miniature donkey with severe bilateral congenital flexural deformities of the metacarpophalangeal and metatarsophalangeal joints were treated successfully by arthrodesis with dynamic compression plating or external skeletal fixation. The flexor tendons were more taut than the suspensory ligaments and were transected. In the llama, the suspensory ligament was transected, and overcorrection caused ischemic necrosis of one distal limb and subluxation of the other fetlock joint. In the horse and donkey, the suspensory ligament was preserved and wedge osteotomy was performed to correct the deformity. PMID- 1626400 TI - A comparison of nylon, polybutester, and polyglyconate suture materials for long digital flexor tenorrhaphy in chickens. AB - Digital flexor tenorrhaphies were performed in 32 8-week-old chickens with polyglyconate, polybutester, or nylon. There was no difference in maximum loads to failure at weeks 4 or 8. Polyglyconate and polybutester tenorrhaphies were significantly stronger at week 8 than all tenorrhaphies at week 4. Nylon tenorrhaphies at week 8 were not significantly stronger than any tenorrhaphy at week 4. The tenorrhaphies consistently had immature scars at week 4 and more mature scars at week 8. Scar maturity was not appreciably different between any of the suture materials at week 4 or week 8. There was no apparent difference in tissue reactivity to any of the suture materials at weeks 4 or 8. PMID- 1626402 TI - Covariances for estimated totals when comparing between years. PMID- 1626401 TI - Hemodynamic function during neurectomy in halothane-anesthetized horses with or without constant dose detomidine infusion. AB - Nine horses were premediated with acepromazine, and anesthesia was induced with guaifenesin and thiamylal. Anesthesia was maintained in four horses with halothane in oxygen, and in five horses with halothane in oxygen plus a constant dose infusion of detomidine. Both maintenance regimens produced a MAC equivalent of 1.4 at the ambient barometric pressure. Hemodynamic and respiratory measurements were made after the horses were anesthetized, during surgical manipulations involving skin or tissues other than nerves, during manipulation and transection of digital nerves, and after surgery while the limbs were being bandaged. Heart rate was significantly higher in horses anesthetized with halothane only than in horses that also received detomidine; there were no other differences in hemodynamic function or recovery characteristics. Respiratory rate was significantly higher than baseline during soft tissue and nerve manipulations; arterial blood pressure was significantly higher after surgery began and highest during neurectomy; cardiac output and cardiac index were significantly decreased during surgery; systemic vascular resistance was significantly increased during neurectomy and bandaging and highest during neurectomy. The data suggest that the increase in blood pressure often associated with surgical stimulation is caused by increased vascular resistance and may be accompanied by a decrease in cardiac output. PMID- 1626403 TI - [Organizational principles of medical and public health measures during a large scale accident at an atomic power station based on the Chernobyl experience]. AB - The whole complex of organizational medical measures on the elimination of aftereffect of the large-scale radiation accident at the NPP may consist of the three basic groups: 1) preventive, aimed at maximally lowering the population and its critical subpopulations exposure levels; 2) curative and diagnostic, which, in addition to the rendering of medical assistance, provide for implementation of the programs of long-term population health studies, and 3) sanitation and educational, aimed at preventing negative social and psychological processes that accompany radiation accidents. PMID- 1626404 TI - [The medico-social significance and forms of introducing the results of program C.27 into public health and national economy practice]. PMID- 1626405 TI - [Chronic radiation sickness in man caused by long-term gamma rays]. AB - A retrospective analysis was made of the leading syndromes of chronic radiation sickness (CRS) induced by external gamma-radiation in a dose of 1.0-9.33 Gy during the disease formation and in the long-term period (30-35 years after diagnosis). The frequency of the hematological and neurological syndromes, secretory alterations in the stomach, efficacy of rehabilitation measures, morbidity in specialists with a history of the clinical manifestations of CRS, who continue working are estimated. The incidence of the main somatic diseases is presented. PMID- 1626406 TI - [The levels of irradiation of superficial tissues in personnel engaged in the clean-up of the consequences of the accident at the Chernobyl Atomic Electric Power Station]. PMID- 1626407 TI - [Means of improving and characteristics of the use of beta spectrometry of 90Sr after the Chernobyl accident]. AB - The paper is concerned with a theoretical possibility of the use of 90Sr beta spectrometry in a mixture of radionuclides including 137Cs, 134Cs, 144Ce and 106Ru after the Chernobyl accident. Special attention is paid to the choosing of a detector and spectrum treatment techniques as factors determining the minimum detectable activity of the method. A brief description of the spectrometric system as well as of the software used is given. The comparison of the method with traditional radiochemical and gamma-spectrometric methods has shown that it is applicable to a wide range of activities and to different objects including those of biological origin. The sources of errors are considered in detail. Approaches to the development of the method are given. PMID- 1626408 TI - [The significance of modifying factors in evaluating the effect of radionuclides]. AB - The authors provide the data obtained in experimental animals, pertaining to the influence of certain modifying factors on metabolism and biological effects induced by radioactive isotopes of iodine, by transuranium elements and beryllium. Out of all the modifying factors investigated, the form of the introduced compound and age turned out the most significant ones. PMID- 1626409 TI - [The relation of non-stochastic effects to the radiation dose of the human thyroid gland]. AB - The paper is concerned with the reported data characterizing the dose-effect relationship for the main non-stochastic effects, namely for acute radiation and chronic thyroiditis and hypothyroidism that occur as a result of external and internal radiation of the thyroid. The threshold doses for acute thyroiditis, hypothyroidism, temporary thyroid hypofunction in adults and children exposed to 131I are estimated. The influence of modifying factors on the intensity and the times of thyroid lesion manifestations such as hyperactive thyroid is under consideration. PMID- 1626410 TI - [Experimental optimization of iodine prophylaxis in an accidental accumulation of radioiodine]. PMID- 1626411 TI - [Dynamics of the radiation conditions and evaluation of the radiation dosage of the inhabitants of Kiev following the accident at the Chernobyl Atomic Electric Power Station]. AB - The estimation of the effective dose equivalents of exposure to accidental and non-accidental sources was made on the basis of the studying of radiation situation variations in Kiev after the Chernobyl accident in 1986-1989. The total annual effective dose equivalents to the Kiev population from all sources of exposure for 1986-1989 were 9.19, 7.29, 5.34 and 5.03 mSv, respectively. The necessity of radiation health measures aimed at limiting the intake of long acting radionuclides of Chernobyl nature and reducing the exposure doses by optimizing the x-ray procedure and by regulating the natural radioactivity of building materials are under discussion. PMID- 1626412 TI - [We must speak up]. PMID- 1626413 TI - [Priority tasks of the common program for the clean-up of the consequences of the accident at the Chernobyl Atomic Electric Power Station]. AB - The paper is concerned with the problems pertaining to the implementation of the State Union-Republic program of urgent measures for 1990-1992 and Republican programs of the elimination of Chernobyl accident consequences. Among the basic priorities covered by the program, the author regards the problems of the living of the population at the polluted areas, criteria for accepting decisions as to the possibility of further living or settling out together with favourable and unfavourable consequences of such a measure as settling out. Emphasis is laid on some priorities of the optimal use of means alloted for implementing the programs of the elimination of Chernobyl accident consequences. PMID- 1626414 TI - [Radiologic consequences and medico-biological problems 4 years after the accident at the Chernobyl Atomic Electric Power Station]. AB - The data on the assessment of the radiobiological situation and the results of clinical and epidemiological studies into the population health status, exposed to radiation because of the Chernobyl NPP accident are summarized. Appropriate regularities in soil contamination with 137Cs are ascertained. It has been shown that the disease incidence among the children's and adult population of the controlled areas is associated not only with improvement of the disease revealing but with the influence of the accident consequences. PMID- 1626415 TI - Biochemical and immunological evidence that the 11 kDa zinc-binding protein of lymphocytic choriomeningitis virus is a structural component of the virus. AB - The completed sequence of the arenavirus, lymphocytic choriomeningitis virus, revealed a new gene encoding a small protein with a single zinc-binding domain. The cDNA for this gene has been expressed in E. coli to produce fusion protein that has been used to raise antisera. The antisera facilitated the positive identification of the p11 'Z' gene product as a structural component of the virion. A related arenavirus, Tacaribe, has a comparable p11 gene product. The abundance of the p11 Z protein relative to other virion components has been determined by metabolic labeling. Triton X-114 extraction and dimethyl suberimidate-HCl crosslinking indicate that the p11 Z protein is a hydrophobic protein associated with the nucleocapsid of the virion core. PMID- 1626416 TI - Rapid treatment of whole cells and RNA viruses for analysis of RNA by slot blot hybridization. AB - To avoid extensive manipulation for the purification of RNA from cells, several methods were evaluated for the direct release of RNA from influenza virus infected cells and supernatants using slot blot hybridization and non-radioactive probes. Treatment with an equal volume of 10 M aqueous guanidine hydrochloride produced the best hybridization signal. Less, but significant amounts of RNA were also released using the following treatments: dilute alkali (final concentration of 0.16 M NaOH) or 100 degrees C/5 min or RNA sample buffer containing formamide/formaldehyde, then heating at 65 degrees C/10 min. Despite the presence of large amounts of cell debris, RNA from guanidine hydrochloride treated whole cell extracts bound quantitatively to the positively charged nylon membranes. The sensitivity of RNA detection when whole cell extracts treated with guanidine hydrochloride were probed with a digoxigenin labelled cDNA probe was similar to the detection of RNA in highly purified, protein free samples. Three positively charged membranes were tested (from Amersham, ICN and Boehringer Mannheim) using two alkaline phosphatase substrates, NBT-X phos, and a chemiluminescent substrate, 3-(2'-spiroadamantane)-4-methoxy-4-(3'-phosphoyloxy)-phenyl- 1-1,2 dioextane (AMPPD) and a peroxidase substrate, tetramethylbenzidine (TMB). The Boehringer Mannheim membrane had the highest sensitivity for the alkaline phosphatase substrates, but the peroxidase reaction with the TMB substrate was the most consistently sensitive, irrespective of which membrane was used. The ability to quantitatively detect RNA from whole cells without any purification will allow the rapid screening of large numbers of samples for specific RNA species in research or diagnostic laboratories. PMID- 1626417 TI - Host dependence of naturally occurring temperature-sensitive influenza A viruses and location of their genetic lesions. AB - Naturally occurring temperature-sensitive (ts) strains have been found in large number in human influenza A viruses of all subtypes (J. Virol. 41 (1982) 353). Further studies have demonstrated that the ts phenotype of these viruses is host dependent in that they are highly ts in chick embryos and chick embryonic cells, but are ts+ in MDCK cells. Previous studies have located by complementation tests the ts lesion of two H3N2 viruses (HK/8/68 and Ningxia/01/72, also known as Xia ts) on the NP gene and that of two H1N1 viruses (Tianjin/78/77 and Beijing/1/79) on the M protein gene. By recombination and polyacrylamide electrophoresis migration of the RNA segments of its ts+ recombinant with PR8, the ts lesion of a later H3N2 virus A/Qi/39/79 has now been located on the M protein gene. The possibility for Qi/39/79 of acquiring the M gene lesion by reassortment with concurrently circulating Tianjin/78/77-like (H1N1) virus which also has ts lesion on the M gene was investigated. In contrast to Tianjin/78/77 (H1N1), however, Qi/39/79 complemented well with ts 51, a WSN ts strain with a single M gene lesion. Qi/39/79 and Tianjin/78/77 also complemented each other. Thus, there are two intra-segmental complementation groups of the M gene: Qi/39/79 belongs to one complementation group, while WSN ts 51 and Tianjin/78/77 belong to another. At present, there is no evidence of reassortment involving the genes concerned in the ts lesions of H3N2 and H1N1 viruses under natural conditions. PMID- 1626419 TI - Reconstitution of influenza virus RNA polymerase from three subunits expressed using recombinant baculovirus system. AB - Influenza virus RNA polymerase catalyzes multiple step reactions in transcription and replication of the genome RNA. The core enzyme is composed of each one of the three P proteins, PB1, PB2 and PA (Honda et al. (1990) J. Biochem. 107, 624-628). For detailed analysis of the role of each P protein and of the functional domains on each P polypeptide, we expressed individual P proteins in cultured insect cells after infection with recombinant baculoviruses. PB1 and PB2 accumulated in cell nuclei whereas PA stayed in cytoplasm. Both the PB1 and PB2 proteins were purified from aggregates in the respective nuclear extract, and the PA was partially purified from the cytoplasm. RNA polymerase was reconstituted by mixing the three P proteins in a urea solution and then dialyzing against a reconstitution buffer. The reconstituted enzyme was able to transcribe model RNA templates. Minus-sense RNA was a better template than plus-sense RNA. PMID- 1626418 TI - Enzymatic properties of the mouse Mx1 protein-associated GTPase. AB - Murine Mx1 protein, an interferon-inducible nuclear protein present in inbred mouse Mx+ strains, confers resistance to influenza virus infection. The purified Mx1 protein was found to carry the activities of both GTPase and GTP-binding. Enzymatic properties of the Mx1-associated GTPase were examined using the Mx1 protein purified from Escherichia coli expressing Mx1 cDNA. The Mx1 protein exhibited a substrate preference for GTP. The Vmax of ATP hydrolysis was about 7.6% the rate of GTP hydrolysis. The hydrolysis of CTP and UTP was virtually negligible. The Km for GTP hydrolysis was 667 microM and the rate was 13.8 mol GTP hydrolysis per min per mol Mx1 protein. The enzymatic properties of Mx1 protein-associated GTPase were compared with those of the GTPase super-gene family and the Mx-related family. PMID- 1626420 TI - Regulation of pH by the M2 protein of influenza A viruses. AB - Inhibition of the function of the M2 protein by amantadine can cause a conformational change in the haemagglutinin (HA) of H7 influenza A viruses and the consequent expression of the low pH form of the glycoprotein on the surface of virus-infected cells. Immunofluorescence studies showed that this conversion occurs shortly after HA exists from the Golgi complex apparently during its transport through the trans Golgi network and using the pH probe, DAMP/anti-DNP, that it is the direct result of reduced vesicular pH. The lowest pHs encountered were estimated using mutant HAs differing in pH stability to be approximately 5.2 and 5.6 in virus-infected CEF or MDCK cells, respectively, in the absence of functional M2. Depending on the particular M2, this protein was responsible for increases in vesicular pH of up to 0.8 units. The influence of mutations in both HA and M2 on the maturation of native HA illustrates the important relationship between the structural and functional properties of these two proteins. Using the fluorescent probe SNARF-1 the M2 protein was also shown to be largely responsible for the 0.3-0.4 unit reduction in intracellular pH of virus-infected cells. The data thus provide further evidence for the pH regulatory function of M2 and its importance for the maturation of the HA glycoprotein. PMID- 1626421 TI - Host range determination and functional mapping of the nucleoprotein and matrix genes of influenza viruses using monoclonal antibodies. AB - Construction and comparison of phylogenetic trees, the standard approach to determining the host-specific lineage of influenza A virus genes is tedious and expensive. In this study, panels of monoclonal antibodies (Mabs) produced against the matrix proteins (M1) of A/WSN and A/PR/8/34 and the nucleoprotein (NP) of A/WSN were assessed for their value in identifying the hosts of origin of the M1 and NP genes in influenza virus isolates and in mapping the proteins' functional domains. Using ELISA against a broad spectrum of reference viruses, we found two Mabs against the NP (150/4 and 469/6) to be useful in determining host-specific lineage. Comparative sequence analysis placed five amino acids within the antigenic domains recognized by Mab 150/4 and two amino acids within the domains recognized by 469/6. One Mab against the NP (5/1) recognized a conserved epitope that is present on each of the 36 influenza A viruses tested. This epitope may be a type-specific determinant for influenza A viruses and an RNA binding site. Monoclonal antibodies to M1 did not discriminate among species, but they did contribute information to the construction of a functional map of M1. These results demonstrate that Mabs to defined protein epitopes can provide useful information on the molecular epidemiology of influenza viruses. PMID- 1626422 TI - Marburg virus, a filovirus: messenger RNAs, gene order, and regulatory elements of the replication cycle. AB - The genome of Marburg virus (MBG), a filovirus, is 19.1 kb in length and thus the largest one found with negative-strand RNA viruses. The gene order - 3' untranslated region-NP-VP35-VP40-GP-VP30-VP24-L-5' untranslated region-resembles that of other non-segmented negative-strand (NNS) RNA viruses. Six species of polyadenylated subgenomic RNAs, isolated from MBG-infected cells, are complementary to the negative-strand RNA genome. They can be translated in vitro into the known structural proteins NP, GP (non-glycosylated form), VP40, VP35, VP30 and VP24. At the gene boundaries conserved transcriptional start (3' NNCUNCNUNUAAUU-5') and stop signals (3'-UAAUUCUUUUU-5') are located containing the highly conserved pentamer 3'-UAAUU-5'. Comparison with other NNS RNA viruses shows conservation primarily in the termination signals, whereas the start signals are more variable. The intergenic regions vary in length and nucleotide composition. All genes have relatively long 3' and 5' end non-coding regions. The putative 3' and 5' leader RNA sequences of the MBG genome resemble those of other NNS RNA viruses in length, conservation at the 3' and 5' ends, and in being complementary at their extremities. The data support the concept of a common taxonomic order Mononegavirales comprising the Filoviridae, Paramyxoviridae, and Rhabdoviridae families. PMID- 1626423 TI - Gene junction sequences of bovine respiratory syncytial virus. AB - The nucleotide sequences of seven gene junctions (N-P, P-M, M-SH, SH-G, G-F, F-M2 and M2-L) of bovine respiratory syncytial virus (BRSV) strain A51908 were determined by dideoxynucleotide sequencing of cDNAs from polytranscript mRNAs and from genomic RNA. By comparison with the consensus sequences derived from human respiratory syncytial virus (HRSV) mRNAs, gene-start and gene-end sequences were found in all BRSV mRNAs. There was a perfect match between the BRSV and HRSV in all gene-start sequences, except for the sequence of the SH gene which contained one nucleotide difference compared to HRSV A2; and the gene-start sequence of the L gene, which was one nucleotide shorter than the corresponding sequence of HRSV. Analysis of the intergenic regions showed a high degree of divergence in the nucleotide sequence between BRSV and HRSV. However, the length of the nucleotides in the intergenic sequences was similar for a given gene junction. As in the case of HRSV, the M2 and L genes of BRSV overlap by 68 nucleotides, suggesting a similar transcription attenuation mechanism. The sequences of the overlap, corresponding to the 3' end of the L gene, were almost identical between BRSV and HRSV. PMID- 1626424 TI - Comparison of the deduced gene products of the L, M and S genome segments of hantaviruses. AB - The amino acid sequences deduced from all currently available nucleotide sequences of hantaviruses are compared. Comparisons of three large (L), eight medium (M) and five small (S) genome segments are included. A consensus sequence is provided, allowing easy identification of conserved and unique gene regions. The viruses included in this report represent four serologically distinct hantaviruses which are capable of causing severe, moderate, mild or no human disease. PMID- 1626425 TI - Nucleocapsid specific T and B cell responses in humans after rabies vaccination. AB - The importance of the immune response directed to the internal component of the rabies virus, the nucleocapsid (NC), was evaluated in humans after rabies vaccination. T cell activation was measured with a bulk proliferative assay and relative frequencies of circulating NC-specific PBL were calculated with the limiting dilution technique. Vaccinees were classified into two groups: NC responders and NC non-responders. In NC responders, the frequency of NC-specific circulating lymphocytes was up to 6 times higher than the frequency of virus specific lymphocytes. In non-responders, NC-specific lymphocytes were up to 25 times less common than virus-specific ones. The NC capacity to induce a secondary antibody response was tested in vitro. After a stimulation with complete virus, lymphocytes originating from donors vaccinated with tissue culture vaccine produced a secondary antibody-response composed mainly of glycoprotein-specific neutralizing antibodies, whereas lymphocytes from suckling mouse brain vaccines produced essentially NC-specific antibodies. This result confirmed the serological status of suckling mouse brain vaccinees, who usually developed high titres of NC-specific antibodies. After an in vitro NC stimulation, lymphocytes collected from NC responders produced not only NC-specific antibodies, provided they have NC-specific B cells at the time of blood sampling, but most surprisingly, they also produce glycoprotein-specific neutralizing antibodies. This finding indicates that NC free of glycoprotein is capable, in some individuals, of boosting an heterologous glycoprotein response. PMID- 1626426 TI - Influenza A virus NP protein expressed in insect cells by a recombinant baculovirus is associated with a protein kinase activity and possesses single stranded RNA binding activity. AB - Influenza A virus NP protein, the phosphoprotein associated with viral RNA in ribonucleoprotein (RNP) complexes, has been expressed at high levels (approximately 100 mg/liter cells) in insect (Sf9) cells by a baculovirus recombinant, and was localized almost entirely in the nuclei of these cells. NP was purified by immuno-affinity chromatography, and purified NP was shown to autophosphorylate and to phosphorylate casein in a cAMP-independent reaction. Furthermore, purified NP was able to bind to ssRNA as demonstrated by a mobility shift of ssRNA in non-denaturing gels. The binding of NP to ssRNA caused a diminution of its kinase activity in proportion to binding. PMID- 1626427 TI - Isolation and sequence analysis of the gene encoding translation elongation factor 3 from Candida albicans. AB - The structural gene encoding translation elongation factor 3 (EF-3) has been cloned from a Candida albicans genomic library by hybridization to a Saccharomyces cerevisiae probe containing the Saccharomyces gene, YEF3 (Sandbaken et al., 1990b). The sequences were shown to be functionally homologous to the Saccharomyces gene by three criteria: (1) a Saccharomyces strain transformed with a high copy plasmid containing CaEF3 sequences overproduces the EF-3 peptide two fold; (2) extracts from this strain exhibit a two-fold increase in the EF-3 catalysed, ribosome-dependent ATPase activity (Kamath and Chakraburtty, 1988); and (3) the Candida gene complements a Saccharomyces null mutant. The coding region, identified by DNA sequencing, indicates that CaEF3 encodes a 1050 amino acid polypeptide having a potential molecular weight of 116,865 Da. This protein shows 77% overall identity to the Saccharomyces YEF3 gene, with a significantly greater identity (94%) concentrated in the region of the protein thought to contain the catalytic domain of EF-3 (Sandbaken et al., 1990a). The upstream non coding region contains T-rich regions typical of many yeast genes and several potential RAP1/GRF1 elements shown to regulate expression of a number of translational genes (Mager, 1988). The data confirm a high degree of conservation for EF-3 among the two organisms. PMID- 1626428 TI - N-linked glycosylation of proteinase B precursors of the yeast Saccharomyces cerevisiae is not required for proper targeting or processing of the enzyme. AB - Proteinase B precursors are modified by an N-linked carbohydrate side chain at Asn 314. Glycosylation at this position is not required for proper localization, processing, or activation of the enzyme. PMID- 1626429 TI - Genetic analysis of maintenance and expression of L and M double-stranded RNAs from yeast killer virus K28. AB - The killer phenotype expressed by Saccharomyces cerevisiae strain 28 differs from that of the more extensively studied K1 and K2 killers with respect to immunity, mode of toxin action and cell wall primary toxin receptor. We previously demonstrated that the M28 and L28 dsRNAs found in strain 28 are present in virus like particles (VLPs) and that transfection with these VLPs is sufficient to confer the complete K28 phenotype on a dsRNA-free recipient cell. We also demonstrated that L28, like the L-A-H species in K1 killers, has [HOK] activity required for maintenance of M1-dsRNA, and predicted that M28 would share with M1 dependence on L-A for replication. We now confirm this prediction by genetic and biochemical analysis of the effects of representative mak, ski and mkt mutations on M28 maintenance, demonstrating that M28 replication resembles M1 in all respects. We also show that L28 is an L-A-H species lacking [B] activity, and that M28 excludes both M1 and M2 from the same cytoplasm. Stable coexpression of K28 phenotype from M28 and of K1 phenotype from an M1-cDNA clone was demonstrated. Exclusion, therefore, acts at the level of dsRNA replication, presumably reflecting competition for the L-A-H encoded capsid and cap-pol fusion protein, rather than reflecting incompatibility of toxin or immunity expression. Finally, we show that expression of active K28 toxin, but not of K28 immunity, requires the Kex2 endoprotease. PMID- 1626430 TI - Identification of RAD16, a yeast excision repair gene homologous to the recombinational repair gene RAD54 and to the SNF2 gene involved in transcriptional activation. AB - The RAD54 gene of Saccharomyces cerevisiae is involved in the recombinational repair of DNA damage. The predicted amino acid sequence of the RAD54 protein shows significant homologies with the yeast SNF2 protein, which is required for the transcriptional activation of a number of diversely regulated genes. These proteins are 31% identical in a 492-amino acid region that includes presumed nucleotide and Mg2+ binding sites. We noted previously that the SNF2 protein also shares homology with a partial open reading frame (ORF) that was reported with the sequence of an adjacent gene. This ORF also shares homology with the RAD54 protein. To test whether this ORF is involved in transcriptional activation or DNA repair, yeast strains deleted for part of it have been isolated. These strains do not show a Snf-like phenotype, but they are UV sensitive. This gene has been identified as RAD16, a gene involved in the excision repair of DNA damage. Analysis of the rad16 deletion mutations indicates that RAD16 encodes a non-essential function and is not absolutely required for excision repair. Outside the region of homology to RAD54 and SNF2, the predicted RAD16 protein contains a novel cysteine-rich motif that may bind zinc and that has been found recently in eleven other proteins, including the yeast RAD18 protein. The homologies between RAD16, RAD54 and SNF2 are also shared by several additional, recently isolated yeast and Drosophila genes. PMID- 1626431 TI - Molecular analysis of yeast chromosome II between CMD1 and LYS2: the excision repair gene RAD16 located in this region belongs to a novel group of double finger proteins. AB - We have analysed a region some 30 kb centromere distal from PHO5 on the right arm of yeast chromosome II and determined the nucleotide sequence of a 8.95 kb DNA segment from this region. By this analysis we were able to derive the precise location and the transcriptional orientation of CMD1, ALG1, SSN6 and LYS2. An open reading frame of 2370 bp was localized between SSN6 and LYS2, which has recently been identified (Schild et al., 1991) to be the RAD16 gene. The putative gene product, 790 amino acids in length, reveals several interesting features. It contains a nuclear target signature and shares several blocks of similarity with the yeast recombinational repair protein RAD54 and the nuclear factor SNF2 (SWI2), which is required for the transcriptional activation of a number of yeast genes. The similarity blocks in these three proteins are reminiscent of those found in the helicase superfamily. Furthermore, RAD16 contains a novel 'double finger' motif, which has been encountered in a variety of proteins from different organisms that are suggested to interact with DNA and are involved in diverse functions including site-specific recombination, DNA repair, and transcriptional regulation. The putative gene product of RAD16 then is the first example of a protein in which the novel double-finger motif is found to be combined with a potential DNA helicase framework. PMID- 1626432 TI - The complete sequence of a 10.8 kb segment distal of SUF2 on the right arm of chromosome III from Saccharomyces cerevisiae reveals seven open reading frames including the RVS161, ADP1 and PGK genes. AB - We have entirely sequenced a 10,835 bp segment of the right arm from chromosome III contained in the J11D and J11D-K3B GF clones. The segment contains seven open reading frames longer then 100 amino acids. Three of them, RVS161 (Urdaci et al., 1990; Crouzet et al., 1991), ADP1 (Purnelle et al., 1991) and PGK1 (Hitzeman et al., 1982) have been described previously. YCR10C encodes a putative membrane protein. YCR8W (encoding a putative protein kinase) and YCR14C extend inside the D10H (Skala et al., 1991) and 62B5-2D clones respectively. Four ARS elements previously reported by Palzkill et al. (1986) are located between RVS161 and YCR10C. PMID- 1626433 TI - Sequence of the novel essential gene YJU2 and two flanking reading frames located within a 3.2 kb EcoRI fragment from chromosome X of Saccharomyces cerevisiae. PMID- 1626434 TI - [Fetomaternal signal transduction by growth factors]. AB - An attempt was made to review the current knowledge on the role of growth factors in the field of fetomaternal interaction. Of special interest was the relation between maternal T-lymphocytes and fetal growth. Stimulation of cytotrophoblast growth is effected by: IGF I/II (insulin-like growth factor), CSF-1 (colony stimulating factor), EGF (epidermal growth factor), FGF (fibroblast growth factor), IL-1, IL-3 (Interleukin), PDGF (platelet derived growth factor). TNF (tumor necrosis factor) inhibits trophoblast cell growth. TNF is synthesized in both decidual and chronic cells. CSF-1 considered the most potent stimulator of the induction of trophoblast cell growth. Cytotrophoblast itself produces IGF I/II, EGF, PDGF, TGF (transforming growth factor). Furthermore, it is known that HCG-secretion is mainly stimulated by IL-1. Whereas intra- and paracrine mechanisms in the placenta will remain in the field of basic research for the next future, animal experiments proving the positive impact of IL-3 and GM-CSF (granulocyte/macrophage-colony stimulating factor) on trophoblast growth should give reason for clinical investigations. It is assumed, that maternal T lymphocytes realize paternally inherited alloantigenic structures resulting in local response of IL-3 and GM-CSF production. PMID- 1626435 TI - [Immunologic aspects of endometriosis]. AB - In development of endometriosis immunological phenomenons are discussed. In women with endometriosis specific antibodies are demonstrated and it is worth to speculate that there takes place de novo-expression of specific antigens. It is also possible, that changes in humoral immunity in endometriosis are secondary to deficient cellular mechanisms. PMID- 1626436 TI - [Evaluation of the efforts in prenatal care for the prevention of prematurity]. AB - A retrospective analysis was done in 341 singleton premature deliveries to assess the practised activities in antenatal care for the prevention of premature delivery. This analysis, expressed in terms of adequacy revealed that 56% were adequate whereas 23% were conditionally adequate and 21% were inadequate. Clinically these activities were reflected in suppression of uterine contractions (80%/57%/40%-effective tocolysis), achieved prolongation of pregnancy (25d/8d/2d) and a lowered rate of premature delivery before the 32nd week of gestation (17%/31%/33%), respectively. A prospective study depending on these results (n = 450) done in 4 centers for antenatal care (under constant supervision to keep the respective recommended activities) showed a significant reduction in the rate of premature delivery compared to a similar control group (n = 458) in the year 1988. Simultaneously, we could demonstrate the influence of patient explanation and the growing patient satisfaction which resulted in reduction of premature delivery. PMID- 1626437 TI - [Ultrasound diagnosis of fetal lung maturity--a new method]. AB - First results are presented to determine the maturity of fetal lung by sonography. Using the fetal liver as a reference-organ we are avoiding the known pitfalls which made it impossible in the past to standardize the fetal lung changes depending on the age of gestation. We examined 104 patients between week 27 and week 41. In one ultrasound section cut we depicted as well lung and liver. According to the known A-mode we registered frequencies in both organs. The registered frequencies were entered digitally into a computer and checked for f(mean), f(max) and f(min). Afterwards the frequencies of the lung were divided by those of the liver. Of all weeks of gestation the mean value and standard deviation were calculated. We found the liver as an adequate reference-organ, since there is no change of the reflection pattern between the different weeks of gestation, while there are significant changes to be registered in the fetal lung, a cutting line being week 35. A quotient of f(mean) lower than 1.1 hints to lung maturity while values over 1.1 point to immaturity. This was confirmed by several cases of analysis of amniotic fluid (L/S-ratio). Further comparisons with amniotic fluid results will have to validate these findings. PMID- 1626438 TI - [Doppler ultrasound study of breast tumors using color Doppler ultrasound, duplex ultrasound and the CW Doppler ultrasound]. AB - The preoperative examinations by doppler-sonography of 83 patients with tumors of the breast are presented. The examinations are done with newest technique: duplex sonography in slow-flow-technique (AI 3200, Dornier); colour-sonography in MEM technique (AI 5200, Dornier) and synchronical colour-doppler++ (Quantum 2000, Siemens) and CW-doppler-sonography (Vasocope 3, Kranzbuhler). There is a markable difference between the side of carcinoma and the normal side as well as pre- and postmenopausal patients. No difference is shown in cases of benign tumors and the normal side. The increasing blood flow of a malignant tumor is showed in changing the doppler parameters (A/B-ratio and resistance-index) and in the doppler wave form. The number of vessels found in or around a tumor is not a good criteria to find malignant diseases, the best criteria is the difference between sides of the mamma. PMID- 1626439 TI - [Therapy of primary fallopian tube cancer--a retrospective study of 30 cases]. AB - Between the years 1968-1988 30 patients with primary carcinoma of the fallopian tube were treated in the Department of Obstetrics and Gynecology of the University of Kiel. In 27 cases the initial treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy. In 3 cases where the patients had undergone surgical treatment in another hospital a second operation for completion was performed. 2 patients received no further treatment after surgery. Postoperative radiotherapy was given to 20 patients and a combined treatment with radiation and polychemotherapy was implemented in 5 cases. Postoperative treatment in 3 patients was poly-chemotherapy alone. The 5-year survival rate taking all tumor stages and modes of therapy employed into consideration was 36.7%. In analysing the survival rate for small numbers as directly related to postoperative treatment a 5-year-survival rate for radiotherapy of 35% (7/20) and for radiation therapy plus poly-chemotherapy of 40% (2/5) was found. After operative treatment followed by poly-chemotherapy alone one of three patients survived after 5 years. PMID- 1626440 TI - [Virucidal disinfection in gynecology]. AB - The different structure and stability of viruses requires the application of virucidal disinfection procedures in gynaecology. For this purpose disinfectants should be used which are tested according to the guidelines of the German Association for the Control of Virus Diseases (DVV; Deutsche Vereinigung zur Bekampfung der Viruskrankheiten) in a virus suspension test and in nearly all cases only a slight increase of application conditions is necessary to get equal efficacy for the disinfection or surfaces of instruments. But the application solutions of instrument disinfectants should not be used longer than one day. Experiments testing the virucidal effectivity of such solutions showed an insufficient decontamination of infectious materials already after 3 days usage. PMID- 1626441 TI - [Congenital cervico-vaginal atresia and pelvic endometriosis. Clinical case and review of the literature]. AB - Congenital cervico-vaginal atresia is a rare malformation; the presence of a functioning endometrium combined with this anomaly causes a retrograde menstruation and then a greater likelihood of endometriosis. Up to the present literature relates only thirteen cases in which congenital cervico-vaginal atresia was combined with a functioning endometrium. Primary amenorrhea and cyclic, cramping lower abdominal pain was the common symptoms of all the patients. In this work we report a new case of such pathology in a 23 old woman affected also by harmonic nanism. After the review of the literature the embryologic mechanisms involved in lower Mullerian tract malformations, the surgical treatment and the mechanism of formation of endometriosis in association with an outflow tract obstruction are discussed. PMID- 1626442 TI - Behaviour and the concept of "heritability" axioms of an ethological refutation. AB - This paper discusses the widespread use of heritability calculations in recent behaviour research including behaviour genetics. In the sequel, a radical criticism concerning the basic axioms of the underlying, more general concept itself is presented. The starting point for testing the proclaimed universal validity of this concept stems from a fictitious yet realistic example taken from learning research. The theoretical result, based on the application of the conventional reasoning in this field, states that developmental processes--and learning is only one specific case out of an immense number of similar behavioural mechanisms--can neither be adequately described nor causally explained with sufficient reliability within the context of the heredity paradigm. On the contrary, an inherent inconsistency of the concept itself when applied to behaviour processes is demonstrated. Finally, a conceptual alternative involving a systems-theoretical approach to the problem is presented: In such a perspective it is the concept of "cognition" which represents the adequate explanatory theorem--a theorem in which quantitative processing of "information" from the environment is clearly revealed to belong to a subordinate level of living organization. PMID- 1626444 TI - Evolutionary epidemiology. PMID- 1626443 TI - Cancer as a mechanism of hypermutation. AB - The highly structured mechanisms of cancers, their tendency to occur as a response to environmental stress, and the existence of oncogenes, suggest that neoplasticity may represent more than a biological disfunction. It is proposed that cancer exists as a phylogenetic mechanism serving to promote "hyperevolution", albeit at the expense of the ontogeny, that is similar to a process recently discovered in bacterial mutations. Cell-surface-associated nucleic acid in tumorigenic cells and sperm cell vectorization of foreign DNA indicate the existence of essential mechanisms necessary to the occurrence of cancer mediated hyperevolution. An analysis of the proposed mechanism indicates that for mutagenesis of chemical cytology, stress induced neoplasticity confers an evolutionary advantage of more than two orders of magnitude. PMID- 1626445 TI - The concept of structuregenesis. PMID- 1626446 TI - In vivo and in vitro productions of interleukin-2, interleukin-2 receptor and gamma-interferon in multitransfused thalassemic patients. AB - In vivo and in vitro productions of interleukin-2 (IL-2), IL-2 receptor (IL-2R) and gamma-interferon (gamma-IFN) in 64 multi-transfused thalassemic patients and 20 healthy children were studied. The results were: 1) Increased serum concentrations of IL-2 and IL-2R, and decreased serum concentration of gamma-IFN were found in thalassemic patients when compared to controls. 2) In in vitro study, productions of IL-2, IL-2R and gamma-IFN were much lower in thalassemic patients than in controls. The possible mechanisms for the altered lymphokine productions are discussed. PMID- 1626447 TI - Recombinant human growth hormone (Genotropin) in treatment of children with growth hormone deficiency: the first year observation. AB - Five prepubertal children with previously untreated growth hormone deficiency were enrolled in this trial and treated with authentic recombinant human growth hormone hGH, 0.1 IU/Kg/day, subcutaneously, for one year. All of the children markedly increased their growth rate; the height velocity increased from 3.4 +/- 0.7 cm/yr to 11.3 +/- 2.0 cm/yr during one year's treatment. The height-standard deviation score for chronological age increased from -4.03 +/- 0.52 to -2.70 +/- 0.68. The bone age increased from 5.6 +/- 1.5 year before treatment to 6.4 +/- 1.6 years after one-year treatment. Only one child acquired low titer anti-hGH antibodies during the course of treatment (1:2 to 1:6). No untoward symptoms were complained of by these children and no biochemical abnormalities occurred except transient subclinical hypothyroidism in one child during the treatment course. PMID- 1626448 TI - Factors affecting the severity of neonatal jaundice of unknown etiology: the role of enterohepatic circulation. AB - Jaundice is the most common condition of otherwise healthy, full-term newborns during the first week of life, and Chinese newborns are known to have a higher incidence and severity of neonatal jaundice than Caucasian newborns. This prospective study was designed to examine factors affecting the severity of neonatal jaundice of unknown etiology in the first week of life with special emphasis on the role of enterohepatic circulation. One hundred and thirty-six healthy, full-term newborns were enrolled in this study. Serum bilirubin levels were monitored daily in the morning for the first five days after delivery. Cord blood, postpartal maternal blood, breast milk and infants' stools were analyzed for beta-glucuronidase activity. Infants with serum peak bilirubin level less than or equal to 7 mg/dl had older gestational age, less maximal weight loss and the bilirubin levels peaked at an earlier age than those infants with peak serum bilirubin level more than 7 mg/dl. They also had lower fecal beta-glucuronidase activity in the stool collected at a mean age of 4.5 (+/- 0.6) days. Among the 136 study cases, 92 infants received some maternal breast milk. There was considerable amount of beta-glucuronidase activity in the human breast milk. Yet its presence did not affect the fecal enzyme activity. Mixed breast feeding also did not influence the serum bilirubin level in the first four days of life. However, infants fed dominantly with breast milk had a higher incidence of serum bilirubin level more than 10 mg/dl at five days old than infants fed solely by infant formula.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626450 TI - Influence of maturation on diastolic events of left ventricle in children. AB - To delineate the influence of maturation process on diastolic events of cardiac cycle, we had performed M-mode and Doppler echocardiography in 120 normal subjects aged from 1 hour to 16 years. The isovolumic relaxation period (IVRP, msec), defined as the time interval between the aortic valve closure to the mitral valve opening, was not statistically different in various age groups. Different equations based on individual ranges of cycle length (CL) were disclosed for each of three different age groups, demonstrating a positive linear correlation between IVRP and CL. On the contrary, an equation showing a linear correlation between diastolic total period (DTP, msec) and CL could be applied to all age groups: DTP = 0.58 x CL-75.2 (r = 0.89, p less than 0.001). Similarly applicable to all age groups, the duration of early diastolic filling (D-F, msec) changed with DTP in all age groups by an equation: D-F = 0.57 x DTP + 0.11 (r = 0.93, p less than 0.001). Ratios between the maximal velocity of early (E) and atrial (A) diastolic filling increased gradually with age. This was largely due to an increase in E with maturation, suggesting a depressed early diastolic filling in the young hearts. We conclude that the patterns of diastolic relaxation and filling are heterogeneously affected by the degree of maturation and represent the net results of complex interactions between changing inactivation properties and loading status at various stages. PMID- 1626449 TI - The management of anorectal malformations. AB - From 1982 to 1990, 120 cases of anorectal malformation (84 males and 36 females) were admitted to Mackay Memorial Hospital; 101 cases were corrected surgically. Among these, 40 cases were high (H) or intermediate (I) type, and 61 cases were low (L) type. In the 40 cases of the H and I type, 13 (Group 1) received Stephens' procedure (SPR) and the remaining 27 (Group 2) received Pena's procedure (PSARP). For the L type, translocation anoplasty, cut-back anoplasty and limited PSARP were employed in 10, 45 and 6 cases, respectively. Anorectal continence results were evaluated by Kiesewetter's criteria. In Group 1, the results were good in 25%, fair in 17% and poor in 58%. In Group 2, the results were good in 70% and fair in 30%. In addition to better anorectal continence, the PSARP resulted in a lower rate of major complications. In the L type, the results were excellent without significant difference among the types of surgery employed. PMID- 1626451 TI - A study of genetic leukodystrophies in Chinese children. AB - During 1986 and 1991, we had diagnosed 12 cases with genetic leukodystrophy including 9 cases with metachromatic leukodystrophy (MLD), 1 case with globoid cell leukodystrophy (GLD, Krabbe's disease), 1 case with neonatal adrenoleukodystrophy (NALD), and the other with probable Pelizaeus-Merzbacher disease (P-M disease). The clinical, biochemical, neurophysiological and neuroradiological features were reported. The diagnosis of MLD, GLD, NALD was confirmed by means of the measurement of serum arylsulfatase A activity, leukocyte galactocerebrosidase activity and serum very long chain fatty acids, respectively. The P-M disease was highly suspected according to clinical picture and evoked potential findings. All the brainstem auditary evoked potentials (BAEPs) and the scalp somatosensory evoked potentials (scalp SEPs) studies in 6 patients with MLD, 1 patient with GLD and 1 patient with NALD were abnormal. In patients with MLD or GLD, the nerve conduction velocity (NCV) studies showed moderate to severe slowing suggesting peripheral demyelinating neuropathy. Brain CT in patients with MLD or NALD demonstrated marked lucency in the white matter. Brain CTs in the patient with GLD showed progressive brain atrophy. In conclusion, though final diagnosis of genetic leukodystrophy should be established throughout biochemical studies, the neurophysiological and neuroimaging studies are of value as an aid to early diagnosis, prediction of clinical course and evaluation of prognosis for genetic leukodystrophy. PMID- 1626452 TI - Urinary N-acetyl-beta-glucosaminidase in children with acute renal failure. AB - Urinary excretion of N-acetyl-beta-glucosaminidase (NAG) was measured in random urine as the ratio of NAG to grams of urinary creatinine. Sixteen children with acute renal failure as well as 8 patients without serum creatinine changes after ischemic insults or nephrotoxic hazards were evaluated for their urinary NAG excretion. For children without renal failure, there was a significant increase (p less than 0.001) in urinary NAG after insults. The urinary NAG returned to normal within 2 weeks. In children with acute renal failure, the mean peak serum creatinine was 3.6 +/- 2.0 mg/dl, and the mean duration between onset and the time serum creatinine returning to normal was 8.8 +/- 4.1 days. Urinary NAG was markedly elevated during acute azotemic stage, remained at high level (p greater than 0.05) after serum creatinine returning to normal, and even continued to be abnormal several weeks after clinical recovery. Corrected with age, the mean urinary NAG level was elevated 6 times above normal after insults in patients without renal failure, and 34 times greater than normal in children with acute renal failure (p less than 0.01). We suggest that the extent of elevation of urinary NAG may be used to monitor the development of acute renal failure in patients exposed to potentially nephrotoxic hazards. PMID- 1626453 TI - Intraspinal enterogenous cyst: report of one case. AB - A 13-year-old boy with an intradural extramedullary enterogenous cyst is presented. He presented with progressive weakness of lower limbs. The myelography and computed tomography scan of spinal cord demonstrated an intradural, extramedullary lesion at the spinal level of T 7-9. A cystic lesion was discovered during operation. The cyst caused the spinal cord compression and was related to neurological deficit. Histologically, it was confirmed by Periodic Acid-Schiff and Alcian Blue stain to contain mucin. He recovered very well after surgical removal of the cyst. PMID- 1626454 TI - Kawasaki disease with Reye syndrome: report of one case. AB - A seven-month-old girl was admitted to the Pediatrics Department of Mackay Memorial Hospital with the following symptoms and signs: (1) high fever for more than five days; (2) injection of bilateral conjunctiva; (3) bright red lips with strawberry tongue; (4) edematous change of palms and soles, followed by digit desquamation; (5) an ill-defined, erythematous plaque on the scar of the BCG. Kawasaki disease was diagnosed, and high dose aspirin (100 mg/kg/day) and intravenous gamma-globulin (IVIG) (400 mg/kg/day) were given for four days. The patient was afebrile on the second day after IVIG infusion, and was discharged six days after admission. A small single daily dose of aspirin (10 mg/kg/day) was given after the afebrile days. Unfortunately, vomiting and consciousness disturbance were noted one day after discharge. Laboratory data showed elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT) and ammonia. Hypoglycemia and prolonged PT and PTT were also noted. Reye syndrome was suspected, and the patient was admitted to the intensive care unit for further management. A liver biopsy gave findings consistent with Reye syndrome. In spite of intensive treatment, the infant expired on the second day after admission. In a review of the literature, no correlation between these two syndromes was found. This rare case is presented to warn that Reye syndrome may follow Kawasaki disease when aspirin has been prescribed at a high dose. PMID- 1626455 TI - Primary psoas abscess: report of one case. AB - A 6-year-old girl was admitted to our hospital with the problems of persistent fever, limping gait, and right hip pain. On physical examination, flexion of the right hip with limitation of the range of motion was noted. Tenderness over the right inguinal area was also elicited. Pyogenic arthritis of the right hip was suspected. Aspiration of the right hip joint was negative. Two days later, a careful examination revealed that the Patrick's test was negative and a local tenderness on the right lower abdomen was found. Laparotomy was performed under the impression of retroperitoneal abscess. The postoperative diagnosis was psoas abscess. After surgical drainage and antibiotics therapy, she was discharged 2 weeks later with good condition. PMID- 1626456 TI - Alloplastic facial contouring: surgery of the fourth plane. AB - Plastic surgeons are now better prepared to fulfill the primary goal of facial aesthetic surgery. By manipulating and combining the various new techniques, they can restore, rejuvenate, or enhance facial form and affect aging changes. Infinite variations in facial contour can now be achieved with alloplastic facial implants. By using techniques based on the concepts of zonal anatomy, the facial skeleton can be augmented with a minimum of complications. Alloplastic onlay techniques significantly improve facial contour to correct both hereditary deficiencies in youth as well as aging changes. The use of implants in the "fourth" skeletal plane, as defined by the author, represents the newest favorable manipulation of volume. PMID- 1626457 TI - Art in medical education: especially plastic surgery. AB - The importance of art studies in the training of plastic surgeons has not been well recognized. Presently, very few medical schools offer courses on art or include it in the humanities. Because the study of art is a great experience that helps to develop the trained eye, the inclusion of art in medical education is recommended. For plastic and aesthetic surgeons, art knowledge can greatly add to the development of surgical skill. Courses in drawing, modeling, and casting are recommended along with lectures or seminars on art appreciation. PMID- 1626458 TI - Dermal and facial autografts in facial aesthetic surgery. AB - Results are presented of dermis grafts used in conjunction with surgery for aging changes in the face. During a two-year period grafts were used to correct crease lines in the glabella and nasolabial creases, as well as angles of the mouth and vermilion. Volume of the grafts was well maintained and very few complications occurred. This technique offers better long-term results than can be obtained by collagen or fat injections. The results and techniques are presented in detail. PMID- 1626459 TI - Response to subdermal implantation of textured microimplants in humans. AB - In lieu of the problems involved with the use of foreign substances such as ivory, paraffin, liquid silicone, and collagen, a new subcutaneous injectable device has been developed. This material--Bioplastique--has been developed in an attempt to overcome the shortcomings of previous augmentation materials, most notably absorption, migration, and immunologic rejection. This article presents a longitudinal study of the use of this new microimplant. PMID- 1626460 TI - The sensuous lip. AB - The author uses Zyplast to help increase the volume of the upper or lower lip. It is emphasized that there is a clear bilobulation of the lower lip which creates the appearance of a beautiful mouth. His injection of Zyplast demonstrates a technique that helps to emphasize this bilobulation. PMID- 1626461 TI - A new safe and aesthetic approach to suction abdominoplasty. AB - Suction abdominoplasties are associated with a number of surgical complications, mainly in obese people and diabetic patients. The aesthetic result is often spoiled by poor balance caused by improper distance between the "guide points" of an harmonious abdomen (e.g., minimum of 10 cm between the pubic scar and the umbilicus). Almost all surgical complications are caused by extensive undermining and can be avoided by an en bloc resection without any undermining (the suction lipectomy of the upper flat creates a "mesh undermining" which is almost as efficient). A new neo-umbilicoplasty, described here, can be situated in the "right position" with good aesthetic results. PMID- 1626462 TI - Correction of deep gluteal depression by autologous fat grafting. AB - In the past, the traditional method of contouring the iliac crest and lateral femoral areas has been liposuction or the surgical removal of the bulges. Unfortunately, this method fails to correct the deep gluteal depression juxtaposed at these two sites. Since we use autologous fat grafts to correct contouring deficiencies elsewhere, it seems logical to investigate whether this technique is applicable to correcting this deformity. We have performed autologous fat grafting to the gluteal depression on 12 patients who underwent lipoplasty of the iliac crest and lateral femoral sites. The longest followup was one year. We have found that this method corrects the deep gluteal depression and yields an improved aesthetic contour. This article describes the technique, addresses the problems encountered, and shows postoperative results. PMID- 1626463 TI - External lipoplasty suction device. AB - Most mobile suction devices specially designed for blunt suction lipectomy are to some degree noisy and several of them could be considered expensive. Their exhaust goes out in the operating room (OR). The potential contamination by aerosoles and fumes favor the use of special outlet filters. The author describes the suction equipment he made in 1984. An industrial high-power vacuum pump is placed outside the OR. The suction tubing goes out of the ceiling in the OR. The machine has double remote pedal control. The exhaust vents out at a hidden place in the clinic's garden, where eventually any AIDS or hepatitis virus will die promptly. This equipment has been used in more than 4200 suction lipoplasty procedures with no technical or surgical complications related to the device. PMID- 1626464 TI - An alternative approach to reduction mammoplasty. AB - The female breast can be reduced by a number of operative techniques. Their goal is to transform different deformities into a so-called ideal form. The ideal form is obtained by small changes such as fixing the nipple's position in relation to predetermined anatomical marks. Under certain conditions we have to deviate from the ideal form. In these cases the operative method used is not determined by the deformity but by the desired form. Reduction mammoplasty techniques are just variations of a single method whose principles still need to be defined. PMID- 1626465 TI - Capsular contracture and silicone gel: experimental study. AB - Wistar rats were used to study the effects, if any, of membrane thickness and implant volume of a silicone gel prosthesis on the development of fibrous capsule contraction. A total of 30 miniprosthesis with three different membrane thicknesses and two different volumes were implanted in the subcutaneous space of five animals. One hundred eighty days later the fibrous capsule was resected and histologically analyzed. Different grades of thickness were observed. The statistical analysis of the data indicates that the thickness of the prosthesis' membrane and the implant's volume did not impact significantly on the grade of fibrosis. PMID- 1626466 TI - Quick and simple technique for the anatomical reconstruction of the concha auriculae. AB - Rhinoplasty cases require use of a cartilaginous graft from the concha auriculae. The perfect anatomical reconstruction of the donor area is possible through a quick and simple technique based on the partial reuse of the graft itself. This article describes use of the technique and the excellent results obtained. PMID- 1626467 TI - Minimal suture blepharoplasty: closure of incisions with autologous fibrin glue. AB - Blepharoplasty incisions can be cloned safely with autologous fibrin glue. The fibrinogen, prepared either from a whole-blood or plasmapheresis source, is mixed with commercially available thrombin to form a seal that is both hemostatic and adhesive. The complication rate is low and primarily due to technical factors in the initial cases. When compared with standard suture techniques, the incidence of minor problems such as milia formation was much lower. In select cases, the technique of using fibrin glue and a minimal number of sutures may be useful as an alternative method of wound closure in blepharoplasty patients. PMID- 1626468 TI - [Application of dye enhanced laser photocoagulation in ophthalmology]. PMID- 1626469 TI - [In vitro formation of endothelial cells into capillary-like cords is promoted by keratocytes]. AB - When isolated bovine capillary endothelial cells were co-cultivated with rabbit corneal keratocytes, capillary-like cords extended actively from the capillary endothelial cells in multilayers of keratocytes. The developing cords continued to elongate, branch out and anastomose with each other, forming a capillary-like network by the 12th day of co-culturing. Electron microscopic observation revealed that the cords had tubular structures, which were composed of 3-8 endothelial cells in the multilayers of keratocytes, and that a basal-like matrix was situated on the outer surface of the endothelial cells. The roles of keratocytes in the cord formation by capillary endothelial cells were discussed. This simple in vitro experimental system is proposed as a useful tool in the study of corneal neovascularization. PMID- 1626470 TI - [Human corneal epithelial, stromal and endothelial cells produce interleukin-6]. AB - We have been investigating the production of cytokines in ocular tissues. In this paper, we demonstrated the in vitro production of interleukin-6 (IL-6) by human corneal epithelial, stromal and endothelial cells using enzyme-linked immunosorbent assay (ELISA). In culture supernatant of the stromal cells, the production of immunoreactive IL-6 was induced, depending upon the doses of lipopolysaccharide (LPS) or IL-1 alpha added into the culture. Detectable IL-6 activity in the supernatant of the stromal cells was found 2 hours after addition of IL-1 alpha and the activity increased to a peak level at 48 hours. On the other hand, in the supernatant of the endothelial cells, IL-6 activity was found even in unstimulated-culture, and induced further by LPS stimulation. The molecular weights (MWs) of the IL-6 produced by the epithelial, stromal and endothelial cells were calculated by gel filtration as about 30 kDa. From Western blotting analysis, the MW of IL-6 produced by the stromal cells was also determined to be 30 kDa. PMID- 1626471 TI - [Effect of trigeminal denervation on rabbit corneal epithelium]. AB - To investigate the effects of trigeminal denervation on the corneal epithelium, left postganglionic trigeminal neurotomy via intracranial approach was performed in 22 rabbits. Among 16 rabbits survived successfully, 13 denervated eyes (81%) showed corneal epithelial abnormalities that included 4 epithelial defects and 9 epithelial opacities. The remaining 3 eyes were normal. Histological examination showed many atrophic epithelial cells and the thinning of the corneal epithelial layer in the denervated eyes with corneal opacities. There was no abnormality in corneal stroma or endothelium. The ratio of epithelial to total corneal thickness calculated by a computer-assisted image analyzer was 6.5 +/- 2.1 (%) in control eyes and 3.8 +/- 1.9 (%) in the denervated eyes, the two values being significantly statistically different (p less than 0.001). PMID- 1626472 TI - [The synthesis of cytokines by human lens epithelial cells--interleukin 1 (IL-1), tumor necrosis factor (TNF) interleukin 6 (IL-6), and epidermal growth factor (EGF)]. AB - We proposed the hypothesis that pseudophakic inflammation, including the fibrin reaction, may be caused by cytokines and/or prostaglandins, synthesized by residual lens epithelial cells (LEC). To test our hypothesis, we measured IL-1 alpha, TNF-alpha, IL-6 and EGF in the culture media of human LEC, obtained by capsulotomy during cataract surgery, by ELISA. IL-1 alpha was detected in one of the two pools of 2-week cultures (20.7 pg/10(5) cells), in two of the three pools of 3-week cultures (12.0 pg/10(5) cells and 13.9 pg/10(5) cells), and in one pool of 4-week cultures (11.1 pg/10(5) cells). IL-6 was detected in 1-week culture (195 pg/10(5) cells) and in 7-week culture (81.6 pg/10(5) cells). TNF-alpha and EGF were not detected. During culture, the cells proliferated and underwent fibroblast-like changes on exposure to the plastic wells. IL-1 and IL-6 may be also produced in vivo by residual LEC contacting with posterior chamber lens after cataract surgery, and these mediators may play a role in postoperative inflammation including fibrin reaction. PMID- 1626473 TI - [The tension of zonule and aging changes of ciliary bodies]. AB - The zonular tension was studied in thirty fixed autopsy eyes (7 eyes under 30 years old, 15 eyes seventh decade and 8 eyes over 85 years old) by pulling the lens backward, and the surface structure of the ciliary body was studied histopathologically following the removal of zonular fibers. The tension for breaking zonules was 49.1 +/- 8.0 gm in younger age group, and 35.3 +/- 8.2 gm in older age group. The zonules in the younger age group was statistically stronger than those in the older age group (p less than 0.01). This breaking occurred at the region adjacent to the ciliary body in the younger age group, but at the region adjacent to the lens in the older age group. The internal surface of the pars plicata and the anterior pars plana was characterized by regular meridional ridges and grooves in the younger age group but was irregular in older age group. In the older age group, grooves among the ridges were wide. In the posterior pars plana, spine-like structure was observed learning parallel toward the lens along the course of zonular fibers. These ageing changes of zonules and ciliary body may depend on the load for the accommodation. PMID- 1626474 TI - [Photodynamically induced vitreous liquefaction in vivo]. AB - Photodynamically induced vitreous liquefaction in rabbit eye was investigated. Photosensitizer, riboflavine phosphate, was injected into the vitreous cavity of the rabbit before white-light irradiation. After the irradiation (0, 1, 3, 6 hr) the rabbit vitreous body was separated into gel and liquid portions. The liquid vitreous body was weighed, and the vitreous liquefaction percentage was calculated. One hour irradiation caused 38% of liquefaction of the eye; 3 hr, 50% liquefaction; 6 hr, 59% liquefaction. Although irradiated control eye (without photosensitizer) and the dark adapted control eye (non-irradiated) showed 10-15% liquefaction throughout the experimental period, the liquefaction percentage of the experimental vitreous bodies was significantly larger than that of the control vitreous. Inhibition experiment showed that the radical scavengers (Cu, Zn-superoxide dismutase, catalase, and mannitol) could suppress the photodynamically induced vitreous liquefaction. Results indicated that free radicals, including hydroxyl radical and superoxide anion, which are generated by photosensitizer and visible light irradiation, may contribute to the age-related vitreous liquefaction of humans. PMID- 1626475 TI - [Effects of cadmium on the gene expression of retinoblastoma (Y79) cells in culture]. AB - We examined the effects of cadmium on the mRNA levels of several genes in cultured retinoblastoma (Y79) cells. After Y79 cells were treated with 15 microM CdCl2, RNA was extracted at a given time. The levels of retinoblastoma gene (Rb) mRNA decreased after cadmium treatment, although it was unlikely that the Rb gene product is functional in this cell line. The N-myc gene (oncogene) is constitutively expressed in untreated Y79 cells but its mRNA levels also decreased following cadmium treatment. On the other hand, the mRNA levels of both heat-shock protein (hsp 70) and metallothionein gene, both having physiological protective effects, increased under these conditions. These results indicate that Y79 cells have physiological protective responses to such a heavy metal as cadmium and that both Rb and N-myc gene expressions are down-modulated in the presence of cadmium. PMID- 1626476 TI - [Indocyanine green enhanced photocoagulation in the pigmented rabbit]. AB - We performed histological studies of rabbit eyes after intravenous administration of indocyanine green (ICG) and fundus endophotocoagulation with diode laser at the wavelength of 810 nm. As continuation of our previous experiments in albino rabbits, we used 10 eyes of 5 pigmented rabbits which more simulate human eyes. We created weak photocoagulation spots 5 to 30 seconds after intravenous ICG, 4 mg/kg. Each photocoagulation lasted 0.2 sec and its irradiation power was averaged 170 mW. One hour after photocoagulation, there were no changes in the inner retinal layers. In the choroid, we observed occlusion of the choriocapillaris, destruction or loss of endothelial cells of large choroidal vessels, and stromal edema. One month after photocoagulation, large choroidal vessels had disappeared. Whole choroidal layers were replaced by fibrous scar tissue. The findings seemed to indicate that ICG enhanced photocoagulation effect can be observed in eyes with pigmented retinal pigment epithelium and that irreversible choroidal damages can be induced throughout the whole thickness of the choroid. The observed choroidal damages were less in intensity than those in albino rabbits. PMID- 1626477 TI - [Indocyanine green videoangiography of the choroidal circulation in the experimental retinal opacity induced by blunt trauma]. AB - Retinal opacity was experimentally induced by blunt trauma to the rabbit eye and the damage to the choroidal circulation was investigated immediately thereafter by using indocyanine green (ICG) videoangiography. Ten pigmented rabbit eyes were used. In the early phase, the defect of choroidal inflow (10 eyes), the twitch of the choroidal artery (2 eyes) and the reflux of the vortex vein (5 eyes) could be observed dynamically. The defect of choroidal inflow showed its peak around the point where the choroidal arteries branched off from ciliary arteries and disappeared within a few second to over ten seconds. The reflux from the vortex vein seemed to be important as collateral pathway. In the middle phase, several points of ICG leakage were observed around the apex of the delayed area of choroidal circulation (9 eyes). This ICG leakage was intra-choroidal and seemed to be caused by the breakdown of the great vessels at the outer layer of the choroid. This study indicates that ICG videoangiography could observe various choroidal circulatory disturbances following blunt trauma and may be useful in delineating the pathogenesis of retinal opacity. PMID- 1626478 TI - [Ultrastructural studies of the lamina suprachoroidea in the human eye]. AB - The lamina suprachoroidea of the human choroid was examined by electron microscopy using both thin sections and freeze fracture replicas. The lamina suprachoroidea was composed of 5-10 layers of pigmented cells interspersed with multiple layers of flattened fibroblastic cells. Tight junctions, gap junctions and intermediate junctions were seen between the fibroblastic cells. Tight junctions did not reveal zonula occludens but predominantly isolated types were revealed, as well as several pore-like fenestrations in the attenuated cell processes of the fibroblasts. The characteristic morphological appearance of the lamina suprachoroidea might suggest that the aqueous humour may be able to leak into the extraocular tissues through it. However, the numerous cellular layers and also the junctional complexes between the fibroblasts of the lamina suprachoroidea are likely to produce more resistance to uveoscleral drainage. As the multi-layered arrangement of fibroblastic cells and pigmented cells in the lamina suprachoroidea did not show the cellular barrier, it may be possible that the extraocular substances are able to flow into the eye through it. PMID- 1626479 TI - [The recovery of the local ERG recorded from reattached retina after retinal detachment]. AB - The functional recovery of the reattached retina after retinal detachment was investigated electrophysiologically. Experimental retinal detachment approximately 4 mm in diameter was made in the rabbit eye by injecting Hanks' solution (HS) or sodium hyaluronate (HNa) into the subretinal space. Local ERG (LERG) was recorded from the spontaneously reattached retina by a double-barreled microelectrode. The retinal detachments caused by HA reattached at an average of 321 +/- 56 minutes after making the detachment, while the detachments by HNa at 20.8 +/- 1.8 days. The recovery of the amplitudes of b-wave and slow P III of the LERG was slower and worse in HNa group than in HS group. In both groups, the amplitudes of the b-waves recovered earlier than the slow P IIIs. Result indicated that earlier reattachment is related to favorable recovery of the retinal function, and that the inner retina generating the b-wave restores its function earlier than the distal retina generating the slow P III. PMID- 1626480 TI - [Color sensation of pseudophakic eye from a viewpoint of electrophysiological study]. AB - Monochromatic ERG b-waves were recorded in normal eyes, cataractous eyes and pseudophakic eyes implanted with non-UV or UV IOLs. ERG b-waves were elicited by fourteen monochromatic stimulus lights ranging from 400 to 660 nm under white light adaptation, and spectral response curves were obtained from b-wave amplitudes. Compared with normal eyes or cataractous eyes, the relative b-wave amplitude of pseudophakic eyes was significantly larger in the short wavelength range from blue to green. Except for 400 nm, the spectral response curve of the eyes implanted with UV IOLs was similar to that of eyes implanted with non-UV IOLs. These results suggested that dyschromatopsia might not only occur in eyes implanted with non-UV IOLs but in eyes with UV IOLs. PMID- 1626481 TI - [Confusion lines in dichromatism using various surface colors]. AB - Confusion lines, convergence points, and neutral points in dichromatism were examined using various surface colors. Confusion lines were obtained from 8 cases of protanopia and 24 cases of deuteranopia by color matching with the surface colors of the Farnsworth-Munsell 100 hue test, then regression analysis was carried out on the cross-points of all confusion lines obtained. Convergence points were obtained and neutral points were also calculated. The convergence point obtained from protanopia using surface colors converged to x = 0.811 and y = 0.189, which is a point near Pitt and Judd's convergence point. The confusion line gradient obtained from deuteranopia was steeper than that of Pitt and Judd's line. The convergence point of deuteranopia was x = 1.959 and y = -0.959. Compared with previous reports, it was in the lower right region. The neutral point of protanopia was in the vicinity of 495 nm and that of deuteranopia in the vicinity of 500 nm. These two values were almost the same as the values in Judd's report. Considering the results mentioned above, the neutral point obtained with surface colors was almost the same as that obtained with spectrum color. From the above results, the convergence point was thought to be different from that obtained using spectrum color. In particular, the difference was significant in deuteranopia. PMID- 1626482 TI - [A case of orbital hematic cyst]. AB - A case of orbital hematic cyst is reported. The patient was a 3-year-old boy in whom swelling of the left upper lid and left exophthalmos appeared after blunt trauma in the region of the left eye. A hematoma was thought to be present from upper lid to the orbit. The hematoma was absorbed but the swelling of the eyelid and exophthalmos increased though more than seven days elapsed after the trauma. The existence of the cyst located from the upper lid to the orbital deep portion and collection of blood were confirmed during operation. Histopathologically the cyst consisted of thickened fibrogranulomatous tissue and the inner wall lacked endothelial or epithelial lining. The blood collected in the cyst hardly coagulated and was examined hematologically. Extreme delay of activated partial thromboplastin-time and prothrombin time, extreme decrease of fibrinogen and abnormal increase of fibrin degradation products were recognized. This indicated that the blood in the cyst had been in a localized accelerated fibrinolytic state. The results support the hypothesis of the mechanism leading to the enlargement of hematic cyst proposed by Pearson et al. PMID- 1626483 TI - [A juvenile case of mesenchymal chondrosarcoma originating from soft tissue in the orbit]. AB - Mesenchymal chondrosarcoma is a very rare occurrence in the orbit. A 10-year-old girl presented with right exophthalmos. Computed tomography revealed a round tumor inside the muscular cone of the right orbit. There was a sign of slight calcification inside the tumor. The tumor was surgically removed by the Kronlein Berke procedure. Histopathological examination showed undifferentiated mesenchymal cells and cartilage tissue. A recurrent tumor was found in the same location 34 months after the surgery, which was removed by frontal approach saving the globe with normal function. Histopathology of the recurrent tumor revealed a slight difference from the primary tumor, showing hemangiopericytoma pattern without cartilage components. Immunohistochemical studies of the primary and recurrent tumors showed their cells to be positive for antifactor VIII and S 100, and negative for myoglobin and monoclonal antibody to muscle actin. Electron microscopically these undifferentiated cells had large nucleus and very scanty cytoplasm, mostly containing glycogen granules. This is probably the first description of a juvenile case of mesenchymal chondrosarcoma originating from soft tissue in the orbit. PMID- 1626484 TI - Baroreceptor reflex function in congestive heart failure. AB - Congestive heart failure is characterized by decreased parasympathetic and increased sympathetic nervous system activity. Impairment of baroreceptor reflex function may be relevant to this altered neural profile. The effect of cardiopulmonary and arterial baroreceptor stimulation on corresponding afferent neural activity is reduced in experimental models of heart failure. In addition, the heart rate and blood pressure responses to perturbations in arterial and carotid sinus pressure are less in animals with heart failure than in control animals. Comparable observations have been made in humans. Unloading cardiopulmonary baroreceptors with lower-body negative pressure causes less forearm vasoconstriction in patients with heart failure than in healthy subjects. The chronotropic response to changes in arterial and carotid sinus pressure induced by drug infusions or by use of a neck chamber is attenuated in heart failure. These data suggest that abnormalities in cardiopulmonary and arterial baroreceptor reflex function contribute importantly to altered autonomic nervous system activity in heart failure. PMID- 1626485 TI - Recognition and management of digitalis toxicity. AB - The most important step in the management of toxicity due to any of the cardiac glycosides is its recognition. Despite the development of an accurate clinical assay for serum levels of digoxin greater than 20 years ago, digitalis toxicity remains common and difficult to confirm, even if suspected, due primarily to 2 factors. First, the signs and symptoms of digitalis toxicity, most commonly an abnormal electrocardiogram showing ventricular or atrial arrhythmias, with or without some degree of concurrent atrioventricular block, often also occur in patients with congestive heart failure (CHF) and underlying coronary atherosclerosis who are not receiving a cardiac glycoside. Second, due to digoxin's narrow therapeutic ratio, the marked degree of variability in the sensitivity of individual patients to its toxic effects, and the common problem of obtaining blood samples inappropriately during the early distribution phase following dosing, a serum digoxin concentration often does not serve as a reliable indicator of toxicity. Despite these difficulties in diagnosis, the management of digoxin toxicity has been made much more effective with the widespread availability of F(ab) fragments of anti-digoxin antibodies. This drug provides the clinician with a rapidly acting, safe antidote for all commonly used digitalis preparations. Conventional therapy for digoxin toxicity remains the maintenance of serum potassium levels greater than or equal to 4 mEq/liter, reversal of decompensated CHF or overt myocardial ischemia, attention to serum magnesium levels and the patient's acid-base status, appropriate antiarrhythmics in the event of ventricular arrhythmias, and a temporary pacemaker for high-grade atrioventricular block. Nevertheless, the high specificity and documented safety of the antibody preparation provides a needed safety net for the continuing use of cardiac glycosides as first-line inotropic agents in the modern therapy of chronic CHF. PMID- 1626486 TI - Recognition and management of asymptomatic patients with left ventricular dysfunction. AB - In recent years there have been encouraging developments in the therapy for congestive heart failure. Vasodilator therapy, as an adjunct to digitalis and diuretics, has made a major impact. Vasodilator therapy results in improved left ventricular (LV) ejection fraction, improved functional capacity, and enhanced quality of life. When an angiotensin-converting enzyme (ACE) inhibitor is used, several studies published since 1988 show that these improvements are accompanied by improved survival. Yet many questions remain. Principal among these is how to approach the patient who has significantly depressed LV function, but is asymptomatic or has only minimal symptoms. In these patients the prognosis cannot be based on New York Heart Association (NYHA) functional class, but must reflect objective measurements of ventricular function. Any intervention should be specifically designed to improve survival, since functional capacity and quality of life are apparently unimpaired. On the other hand, there are no data at present to suggest that intervention in these patients will improve survival. This article considers the evaluation of such asymptomatic patients and potential therapeutic approaches. These are the use of cardiac glycosides, the use of ACE inhibitors, or their combination. Circumstantial evidence supporting their use in this select patient population is considered. It is stressed that any decision to intervene therapeutically in the asymptomatic patient must be made by the physician on an individual basis. PMID- 1626487 TI - Management of refractory congestive heart failure. AB - Despite recent advances in the treatment of congestive heart failure (CHF), many patients continue to present with symptoms refractory to digoxin, diuretic, and vasodilatory therapy. Since it is unlikely that this population will decrease in the near future, practical approaches to management of refractory CHF are reviewed. Refractory CHF here is defined as New York Heart Association (NYHA) functional class III-IV heart failure, despite maximal drug therapy. Before such a diagnosis is made, the patient should be treated with digoxin, diuretics, and a vasodilator. Approach to therapy requires assessment of changing clinical status and pathophysiology, optimizing oral drug treatment, and providing temporary parenteral support when indicated. Specific attention should be given to factors that influence the optimal response to each of these 3 treatment classes. A theoretical, but unproven, concept suggests that combined vasodilatory therapy may be appropriate as long as excessive hypotension is avoided. In the course of management, a decision is required as to whether further optimization of therapy can be achieved on an outpatient basis. Hospital-based intravenous inotropic support given for 2-4 days will often provide the opportunity to restructure patient therapy. PMID- 1626488 TI - Long-term strategies in the management of heart failure: looking beyond ventricular function and symptoms. AB - Therapeutic approaches to the management of heart failure have traditionally focused on shortterm hemodynamic and symptomatic goals, but present evidence suggests that most therapeutic decisions have long-term consequences. Treatment may change the rate of disease progression, modify the need for additional therapy, influence the number of hospitalizations, and alter the risk of death. However, there may be little relation between a drug's short-term effect on cardiac function or cardiovascular symptoms and its long-term effect on survival. Some therapeutic interventions favorably influence the outcome of patients with heart failure, even though they exert negative inotropic effects; others adversely affect the outcome of patients, even though they markedly improve cardiac performance. This discordance might be explained if the most important predictor of response to a therapeutic intervention in heart failure were the effect of the pharmacologic agent on neurohormonal systems rather than on hemodynamic variables. In general, drugs that decrease the effects of the sympathetic nervous system (digitalis glycosides) and the renin-angiotensin system (angiotensin-converting enzyme [ACE] inhibitors) reduce the risk of worsening heart failure. Conversely, drugs that potentiate the effects, or increase the activity, of the sympathetic nervous system (phosphodiesterase inhibitors) or the renin-angiotensin system (calcium antagonists) increase cardiovascular morbidity and mortality. These observations suggest that physicians should no longer focus on short-term hemodynamic or symptomatic goals in the treatment of heart failure but, instead, should manage patients to improve both the quality and quantity of life. PMID- 1626489 TI - Reflex cardiovascular control in congestive heart failure. AB - This article reviews evidence that the reflex control of the cardiovascular system provided by negative feedback mechanisms is impaired in congestive heart failure (CHF). The impairment involves vagal and sympathetic modulation of the heart exerted by arterial baroreceptors. It also affects baroreceptor control of blood pressure and peripheral vascular resistance, as well as the cardiopulmonary receptor's ability to modulate sympathetic activity. The degree of such impairment is most marked in severe CHF but is also apparent, to a minor degree, in mild heart failure. Reflex impairment is due to a reduction in the receptor signal, but other factor under investigation are probably also involved. Digoxin and other pharmacologic treatments of CHF improve reflex function, thereby facilitating a reduction in the elevated sympathetic activity and a stepping up of the reduced vagal activity typical of CHF. This may be relevant to a patient's prognosis. PMID- 1626490 TI - Digitalis and neurohormonal abnormalities in heart failure and implications for therapy. AB - A pathophysiologic hallmark of heart failure is neurohormonal excitation, a prominent feature of which is activation of the sympathetic nervous system. Studies from our laboratories demonstrate that clinical heart failure is characterized by marked increases in efferent sympathetic neural outflow to muscle; the magnitude of this sympatho-excitation parallels the degree of cardiac dysfunction. Impairments of cardiopulmonary and arterial baroreflex sensory mechanisms appear to be responsible to a significant degree for this sympatho excitation, consistent with findings in animal models of heart failure. Digitalis glycosides exert modest inotropic actions when administered to patients with heart failure. Digitalis also has potent autonomic effects that can potentiate impaired arterial and cardiopulmonary baroreflex mechanisms in experimental models of cardiac dysfunction. Acute digitalis administration to patients with moderate-to-severe heart failure produces profound and sustained sympatho inhibition, which precedes any observed hemodynamic action of the agent. Further, acute digitalization of such patients rapidly normalizes impaired baroreflex mediated mechanisms. Data now suggest that the mechanism of action of digitalis in humans is an acute potentiation of baroreceptor-mediated afferent regulation of sympathetic neural mechanisms. Prospective, randomized and controlled studies now are required to test the hypothesis that the acute effects of digitalis on autonomic mechanisms also are observed during chronic administration. In theory, the chronic sympatho-inhibitory action of digitalis, combined with its chronic potentiation of impaired baroreflex mechanisms, may offer beneficial effects independent of its inotropic actions in patients with heart failure. PMID- 1626491 TI - Acute hemodynamic effects of digoxin alone or in combination with other vasoactive agents in patients with congestive heart failure. AB - Although digitalis preparations have been in use for greater than 200 years, it is only within the last 2 decades that the central hemodynamic and neurohumoral effects occurring over several hours following intravenous administration of digoxin have been investigated in patients with congestive heart failure (CHF). Although digoxin has been shown to stimulate myocardial contractility in tissue preparations, its positive inotropic activity does not consistently translate into improvements in hemodynamic measurements in humans. Digoxin given intravenously results in increased cardiac index and decreased heart rate, left ventricular filling pressure, and right atrial pressure, as well as in acute attenuation of neurohumoral abnormalities, in patients with chronic CHF who have abnormal baseline hemodynamic measurements. Unlike other drugs with positive inotropic activity, however, digoxin does not influence hemodynamics in normal volunteers or in CHF patients in whom hemodynamics have been normalized with other therapies. These differing effects may be related to the drug's diverse peripheral vascular effects in CHF patients in whom vasodilation may occur in comparison with those that occur in normal subjects in whom the peripheral vasoconstrictor effects may prevent the inotropic effects of the drug from being translated into an increase in cardiac output. The hemodynamic effects of digoxin in patients with chronic CHF due primarily to diastolic dysfunction have not been fully investigated. Intravenous digoxin produces hemodynamic effects in patients with CHF associated with acute myocardial infarction, but these changes are small compared with those resulting from the administration of dobutamine. Digoxin does not appear to influence hemodynamic measurements in patients with right ventricular dysfunction unless concomitant left ventricular failure is present. In patients with chronic left ventricular dysfunction, the hemodynamic effects of intravenous digoxin and vasodilators are enhanced when these agents are given in combination. PMID- 1626492 TI - Review of randomized trials of digoxin therapy in patients with chronic heart failure. AB - Although digitalis glycosides were introduced in the treatment of cardiac maladies greater than 200 years ago, controversy persists regarding the precise role of digoxin in any multidrug approach to the treatment of congestive heart failure (CHF). Despite its widespread use for more than 2 centuries, only recently have double-blind, randomized, placebo-controlled trials of digoxin therapy been conducted in patients with moderate CHF and sinus rhythm. These trials demonstrate that digoxin is superior to placebo in improving left ventricular (LV) ejection fraction, increasing exercise capacity, and preventing CHF worsening. Digoxin produces benefits similar to those seen with angiotensin converting enzyme (ACE) inhibitors with regard to clinical compensation and improvement in LV function. However, improved survival is demonstrated only in response to ACE inhibitors. The recently completed RADIANCE study addresses the value of combining digoxin with ACE inhibitor therapy in patients with mild-to moderate CHF. Because increased mortality has been reported with the newer oral inotropic agents, it currently appears that digoxin is the only oral inotropic agent useful in clinical practice in the treatment of CHF. However, the effects of digoxin on mortality in patients with CHF remain unknown. In the large, double blind, randomized trial conducted by the National Heart, Lung, and Blood Institute, the effects of digoxin on mortality in patients with CHF and already being treated with ACE inhibitors are currently being evaluated. Presently, based on the results of placebo-controlled studies, it appears that digoxin, alone or in combination with ACE inhibitors, is beneficial in patients with any signs or symptoms of CHF due to systolic LV dysfunction. PMID- 1626493 TI - Need for a large randomized trial to evaluate the effects of digitalis on morbidity and mortality in congestive heart failure. AB - Despite major advances in the prevention and treatment of cardiovascular diseases, the incidence and prevalence of congestive heart failure (CHF) have been increasing in recent years. As the average age of the population increases, the prevalence of CHF is expected to continue to increase. The number of deaths in which CHF was considered the underlying or contributing cause increased from 51,000 in 1955 to 274,000 by 1988 in the United States. Even accounting for population growth and an increase in the number of elderly, this represents a 2 fold increase. Additionally, CHF was responsible for about 643,000 hospitalizations in 1988. Digitalis is one of the drugs most commonly prescribed for CHF and has been used for greater than 200 years. In 1990, digoxin was one of the most commonly prescribed drugs in the United States, accounting for greater than 21 million prescriptions. There has been little decline in the drug's use over the last 5 years, indicating that newer treatments for CHF have not replaced the widespread use of digitalis. Despite these findings, considerable controversy surrounds the appropriateness of its role and value in treating CHF patients who are in sinus rhythm. A number of recent, uncontrolled studies have arrived at apparently contradictory conclusions concerning the effects of digitalis on mortality in postmyocardial infarction and heart failure patients. A large, double-blind, randomized, controlled clinical trial to evaluate the effects of digitalis on mortality, morbidity and quality of life is being sponsored by the National Heart, Lung, and Blood Institute in conjunction with the Department of Veterans Affairs Cooperative Studies Program.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626494 TI - Ventricular arrhythmia in congestive heart failure. AB - The importance of ventricular arrhythmia is based on its association with sudden death. In certain groups of patients, ventricular arrhythmia--primarily runs of nonsustained ventricular tachycardia (NSVT)--is associated with an increased risk for sudden death. Although this relationship has been most often reported in patients with recent myocardial infarction, it has also been recognized in patients with dilated cardiomyopathy, regardless of etiology. Therefore, ventricular arrhythmia is common in patients with CHF due to cardiomyopathy. A number of studies have reported that 70-95% of patients with cardiomyopathy and congestive heart failure (CHF) have frequent ventricular premature beats, and 40 80% will manifest runs of NSVT. Many factors are responsible for ventricular arrhythmia in such patients, including structural abnormalities, electrolyte imbalance, hemodynamic impairment, activation of neurohormonal mechanisms, and pharmacologic therapy. Many studies have reported a high yearly mortality in patients with cardiomyopathy and CHF; greater than 40% of deaths are sudden, most often the result of sustained ventricular tachyarrhythmia. Most studies have noted an association between presence (and frequency) of NSVT and risk of sudden cardiac death in these patients. Unfortunately, other techniques--such as the signal-averaged electrocardiogram and electrophysiologic testing--are not helpful in identifying the individual at risk. Although several drug interventions will reduce mortality from progressive CHF, these drugs have not been shown to reduce sudden death and, indeed, have a variable effect on ventricular arrhythmia. Although NSVT is a marker for increased risk for sudden death, it is uncertain if antiarrhythmic drugs will prevent this outcome. Antiarrhythmic drugs have not been shown to be effective for preventing sudden death, although there are as yet no well-controlled randomized trials. Several studies suggest that amiodarone and beta blockers are beneficial, but this requires confirmation. For patients who have been resuscitated following an episode of sudden death due to a sustained ventricular tachyarrhythmia, antiarrhythmic therapy guided by invasive and noninvasive techniques appears to reduce risk of recurrent arrhythmia. However, the response rate to antiarrhythmic agents is low and side effects are common in patients with CHF. Especially important is the increased risk of precipitating CHF and aggravating the arrhythmia being treated. For many such patients who have had serious ventricular tachyarrhythmia, the automatic implantable cardioverter defibrillator may prove a better option. Other drugs used for management of CHF reduce overall mortality, but not risk of sudden death. PMID- 1626495 TI - Clinical use of serum digoxin concentrations. AB - The development of the radioimmunoassay for digoxin by Smith and coworkers in 1969 was a landmark in digitalis therapy. Since then, the complex pharmacokinetics of digoxin have been defined. As a result, the incidence of digitalis toxicity has markedly decreased. To use the digoxin assay properly, however, the relation of this pharmacokinetic parameter to digoxin pharmacodynamics must be known and the limitations of the assay itself understood. Systolic time intervals (STI) are uniquely useful to quantitate the inotropic effect of digitalis preparations. This technique can demonstrate the onset and magnitude of the inotropic effect for both oral and intravenous digitalis administration. By defining the mathematical relation between STI and simultaneous serum digoxin concentrations following intravenous administration of 1 mg digoxin, computer simulations can be made of the effect of dosing changes on blood and tissue concentrations. The serum digoxin assay has technical problems relating to quality control, interference by metabolites, and cross-reactions with endogenous digitalis-like substances. Further, a standard time for measurement following dosing has not been established. Physical activity can significantly after the serum digoxin concentrations by increasing skeletal muscle binding. Numerous drugs can interfere with digoxin absorption or elimination. Using the serum digoxin assay is the only way to assess these interactions. Computer surveillance (ideally with physician or pharmacist interaction) has been used to monitor digitalis but has not yet gained widespread acceptance. This is clearly a method in need of further testing. PMID- 1626496 TI - Effectiveness of low-dose colestipol therapy in patients with moderate hypercholesterolemia. AB - Recommended doses of bile-acid binding resins have an established hypocholesterolemic effect, but data on responses to low doses, especially in women and subjects with moderate hypercholesterolemia, are sparse. A double blind, placebo-controlled, randomized trial of 3 low doses of colestipol hydrochloride was conducted in women and men with moderate hypercholesterolemia. Men and women with plasma low-density lipoprotein (LDL) cholesterol concentrations greater than 4 mmol/liter (155 mg/dl) and triglyceride concentrations less than 2.82 mmol/liter (250 mg/dl) were recruited for the study. Eligible patients (54 women and 98 men) were placed on the American Heart Association step I diet 6 weeks before randomization. Participants were subsequently assigned to 1 of 4 drug treatment groups (placebo, and 5, 10 and 15 g/day of colestipol in 2 divided doses) for an additional 12 weeks. Of the 152 patients randomized, 141 completed all aspects of the study. For the treatment groups--placebo, and 5, 10 and 15 g of colestipol--LDL cholesterol reductions (mmol/liter) were observed respectively (n = 141): 0.10 +/- 0.49 (2.7%), 0.65 +/- 0.41 (16.3%), 0.98 +/- 0.36 (22.8%) and 1.17 +/- 0.47 (27.2%) (p less than 0.001). Similar changes were observed in total cholesterol and apolipoprotein B concentrations. The apolipoprotein B/LDL cholesterol ratio increased significantly with increasing colestipol dosage. Modest but insignificant changes in plasma triglyceride levels occurred, and high-density lipoprotein cholesterol levels remained unchanged. A dose of 5 g/day of colestipol achieved 51% of the LDL cholesterol reduction noted with 15 g/day. Low-dose colestipol therapy is effective in the treatment of patients with moderate hypercholesterolemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626497 TI - Greater diagnostic sensitivity of treadmill versus cycle exercise testing of asymptomatic men with coronary artery disease. AB - Maximal hemodynamic and ventilatory responses using cycle and treadmill ergometer were compared in 52 asymptomatic patients with angiographically proved coronary artery disease. Moreover, test sensitivity with respect to ST-segment depression and typical angina pectoris were compared between exercise modes used. Exercise tests were performed on different days in randomized order. In 42 patients, exercise-induced myocardial ischemia, expressed as a fraction of left ventricular circumference, was assessed by thallium-201 scintigraphy. The main finding of this study was a significantly higher maximal oxygen uptake (1.87 +/- 0.4 vs 2.2 +/- 0.5 liters/min; p less than 0.001), heart rate (148 +/- 19 vs 158 +/- 18 beats/min; p less than 0.001) and rate-pressure product (28.3 +/- 5 x 10(3) vs 30.7 +/- 5 x 10(3); p less than 0.001) during treadmill walking than during cycling. Therefore, stress-induced myocardial ischemia was significantly more extensive after treadmill walking (31 +/- 37 degrees vs 45 +/- 40 degrees; p less than 0.001). Moreover, there were significantly more patients with signs of myocardial ischemia (ST-segment depression or typical angina pectoris, or both) during treadmill than during cycle ergometry (35 vs 25 patients; p less than 0.05). However, lactate levels measured at peak exercise (4.07 +/- 2.0 vs 4.38 +/ 1.9 mmol/liter) and 3 minutes into the recovery period (5.60 +/- 2.2 vs 5.80 +/- 2.2 mmol/liter) were comparable between both methods, indicating no significant difference in anaerobic energy production. These findings suggest that walking on a treadmill represents an exercise method with a greater ability than cycling to detect coronary artery disease. PMID- 1626498 TI - Prognosis in rupture of the ventricular septum after acute myocardial infarction and role of early surgical intervention. AB - Since 1944, 91 patients (50 men and 41 women, mean age 68 years [range 39 to 86]) with ventricular septal rupture after acute myocardial infarction were seen at the Mayo Clinic. Patients were divided into 4 groups according to therapy and timing of surgical intervention. Fourteen patients seen before 1965, when surgery was not performed for such a complication or not readily available, were excluded from the analysis. Group 1 (n = 22) had surgery within 48 hours of septal rupture, group 2 (n = 6) underwent operation between 2 and 14 days, group 3 (n = 24) had surgery after 14 days, and group 4 (n = 25) only received medical treatment. Short-term (30 days) survivors (45%, 35 of 77 patients) were compared with nonsurvivors. Using logistic regression, by univariate analysis, 3 variables were significantly associated with outcome: age (p less than 0.01), cardiogenic shock (p less than 0.00001), and long delay between ventricular septal rupture and surgical intervention (p less than 0.004). By multivariate analysis, however, only cardiogenic shock (p less than 0.00001) and age (p less than 0.007) correlated with an adverse outcome. In patients with cardiogenic shock after septal rupture, the prognosis was uniformly fatal unless patients undergo early surgery. None of the 23 patients in groups 2, 3 or 4 survived, whereas 5 of 13 patients (38%) who had surgery within 48 hours of septal rupture survived.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626499 TI - Prognostic value of changes in R-wave amplitude during exercise testing after a first acute myocardial infarction. AB - To investigate the prognostic value of exercise-induced changes in R-wave amplitude and their relation to other exercise and angiographic variables, 303 consecutive patients who underwent maximal exercise testing and coronary angiography within 2 months of a first acute myocardial infarction were studied. R-wave amplitude at peak exercise increased or was unchanged in 159 patients (57.4%) and decreased in 118 (42.6%). Increased R-wave amplitude was significantly related to underlying 3-vessel disease (p = 0.0001), the extent of ST-segment depression on exercise (p = 0.0001), and the time to 1 mm ST depression (p less than 0.05). Follow-up information was available in 285 patients (86.4%) at a mean of 4 +/- 1.8 years. Death from cardiac causes occurred in 25 patients (9%); 18 (6.5%) developed recurrent myocardial infarction, and 32 (11.6%) developed angina. Variables with a predictive value for cardiac death were maximal exercise heart rate (p = 0.0005), occurrence of exercise-related supraventricular arrythmia (p = 0.02), and number of diseased vessels (p = 0.02). R-wave changes had no predictive value. No variable had a predictive value for recurrent infarction. Maximal exercise heart rate (p = 0.02) and increased R-wave amplitude (p = 0.0001) were significantly related to the occurrence of angina at follow up. Exercise-related R-wave increases were associated with the presence of angina at follow-up, but had no predictive value for cardiac death or recurrent infarction; their association with subsequent angina appears to reflect an association with more severe underlying coronary disease. PMID- 1626500 TI - Effects of captopril on left ventricular systolic and diastolic function after acute myocardial infarction. AB - The left ventricle progressively dilates in some patients after acute myocardial infarction (AMI). Both systolic and diastolic left ventricular (LV) dysfunction can be of significance in the development of heart failure. Captopril has been shown to prevent dilatation, but the effect on LV diastolic function is unknown. In a placebo-controlled double-blind parallel study, 58 AMI patients with heart failure or low ejection fraction, or both, were consecutively randomized at day 7 to either placebo or captopril (25 mg twice daily). No differences were present between the groups at baseline. Fifty-three patients completed the 6-month study period. Both LV diastolic and systolic volume indexes increased significantly in the placebo group (17 and 14%, respectively); in the captopril group there was no change in LV diastolic volume index, but a 13% reduction in LV systolic volume index. Ejection fraction increased significantly in the captopril group. The peak flow velocities of the early and atrial filling phases were measured, and the ratio between the velocities was calculated. A significant reduction was observed during the study period in early peak flow velocity (65 to 52 cm/s) and in the ratio between early and atrial peak flow velocity (1.3 to 0.8) in the placebo group (p less than 0.05), but no significant changes occurred in the captopril group. No correlation was found between dilatation of the left ventricle and reduction in early peak flow velocity or the ratio between early and atrial peak flow velocity. In conclusion, captopril prevented LV dilatation, improved ejection fraction and prevented LV diastolic dysfunction in AMI patients with early signs of LV systolic dysfunction. PMID- 1626501 TI - Acute and long-term outcome of narrowed saphenous venous grafts treated by endoluminal stenting and directional atherectomy. AB - Angioplasty of the narrowed saphenous vein bypass grafts remains a difficult challenge. Over a 37-month period at this institution, 119 of 176 interventions (68%) on saphenous vein grafts (average age 8.3 years from bypass surgery to graft intervention) were performed using either directional coronary atherectomy (n = 35) or Palmaz-Schatz intracoronary stents (n = 84), representing 37% of all stents and 15% of all atherectomies during the study period, respectively. Of the 57 saphenous vein graft lesions treated with conventional balloon angioplasty during this period, 49 (86%) had 1 or more contraindications to stenting or directional atherectomy (thrombus, total occlusion, reference vessel less than 3 mm in diameter). The acute success rate was 99% for stents (1 failure to dilate) and 94% for directional atherectomy (2 failures to cross the lesion with the atherectomy device). Lumen diameter increased from 0.9 to 3.6 mm (reference vessel 3.6) for stents, and from 0.9 to 3.5 mm (reference 3.8) for atherectomy (for all comparisons, p = not significant), with no major complications (abrupt or subabrupt closure, emergent coronary bypass surgery, death, or Q-wave myocardial infarctions). During the same time period 50 of 57 vein grafts (88%) rejected for stenting or atherectomy were dilated successfully by conventional balloon angioplasty, with 3 patients (5%) requiring emergent coronary bypass surgery. Angiographic follow-up was available for 50 of 64 eligible patients (78%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626502 TI - Comparison of accuracy for detecting coronary artery disease and side-effect profile of dipyridamole thallium-201 myocardial perfusion imaging in women versus men. AB - Intravenous dipyridamole planar thallium-201 imaging is a safe and effective test for detection and prognosis of coronary artery disease (CAD) in the general population. The relative diagnostic accuracy and side-effect profile of dipyridamole thallium-201 stress imaging in women is not defined. Forty-three consecutive female and 71 male patients who underwent dipyridamole thallium-201 imaging (0.56 mg/kg) within 3 months of cardiac catheterization were studied. Scans were considered abnormal if fixed or reversible perfusion defects were detected. Stenosis severity of greater than or equal to 50% luminal diameter reduction of any artery defined CAD. Overall sensitivity for detection of CAD was 0.87 in women and 0.94 in men; specificity was 0.58 in women and 0.63 in men (p = not significant). Sensitivity for detection of 1-vessel CAD was 0.60 in women and 0.94 in men (p = 0.001). The sensitivity for detection of multivessel CAD (with or without surgical revascularization) was 1.0 and 0.94 in women and men, respectively. Adverse effects were reported in 62% of women and in 38% of men (p = 0.01). There was no significant difference in the incidences of chest pain, headache, nausea, flushing or electrocardiographic changes. The incidences of severe ischemia and dizziness were higher in women. Possible explanations for this difference in adverse effects include gender differences in the volume of distribution of dipyridamole due to varied fat-to-muscle ratios and different subjective nocioceptive sensitivities to the effects of dipyridamole. Overall sensitivity and specificity are comparable between the sexes. PMID- 1626503 TI - Strategy of complete revascularization in patients with multivessel coronary artery disease (a report from the 1985-1986 NHLBI PTCA Registry). AB - Percutaneous transluminal coronary angioplasty (PTCA) is increasingly performed in patients with multivessel coronary artery disease (CAD) despite reports showing relatively low rates of complete revascularization and poorer long-term prognosis for patients with significant residual narrowings. Reasons for incomplete revascularization were assessed in 618 patients with multivessel CAD in the 1985-1986 National Heart, Lung, and Blood Institute (NHLBI) PTCA Registry. The PTCA operator was asked to describe the treatment plan and outcome for each of the 1,942 significant lesions (greater than or equal to 50% luminal diameter stenosis) in the Registry patients. Although all significant narrowings were considered amenable to balloon angioplasty in 77% of patients, complete correction was intended only for 34% of them. It was attempted in 28% and successful in 19%. Only 63% of total occlusions were considered amenable to PTCA and only 54% of those attempted were successfully dilated. PTCA was intended for 38% with 50 to 69% stenoses versus 80% with 70 to 89% stenoses and for greater than 85% with narrowings greater than or equal to 90%. Dilatation in narrowings of the left circumflex and left anterior descending artery systems was intended less frequently than in lesions of the right coronary artery. Finally, there was wide variability in operator strategy among the different Registry sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626504 TI - Mortality after coronary angioplasty and coronary artery bypass surgery (the national Medicare experience). AB - Mortality rates for Medicare patients who underwent coronary artery bypass surgery were compared with those who had angioplasty or angioplasty and bypass surgery. Two data sets were used for this study: The first contained information on demographic factors, co-morbidities and subsequent mortality on all 96,666 Medicare patients who had bypass surgery or angioplasty in 1985; the second contained additional detailed clinical data collected using the MedisGroups method on a random sample of 2,931 revascularization patients from 6 states. From the national data set 30-day and 1-year mortality rates were 3.8 and 8.2% for 25,423 angioplasty patients and 6.4 and 11.8% for 71,243 bypass surgery patients (p less than 0.001 for both time periods). Mortality rates for the MedisGroups data were 4.4 and 8.5% for the angioplasty patients and 6.5 and 11.9% for the bypass surgery patients. After eliminating patients admitted with a myocardial infarction, mortality rates were 1.9 and 6.0% for 632 angioplasty patients and 5.1 and 10.8% for 1,730 bypass surgery patients. The risk-adjusted relative risk of mortality for bypass surgery versus angioplasty was 1.72 (p = 0.001) for all patients, 2.15 (p less than 0.001) for low-risk patients and 0.90 (p = not significant) for high-risk patients. Results suggest that low-risk patients have better survival with angioplasty because of lower short-term mortality. PMID- 1626505 TI - Cardiac response to combined moderate heat and exercise in men with coronary artery disease. AB - The effect of moderate heat stress on cardiac performance during sustained moderate physical work was evaluated in men greater than or equal to 6 weeks after a cardiac event. Subjects (n = 10) performed upright leg cycle ergometer exercise at approximately 50% of peak oxygen uptake for up to 60 minutes in warm (30.0 +/- 0.9 degrees C) and thermoneutral (21.5 +/- 0.3 degrees C) environments. Cardiac output (carbon dioxide rebreathing method), left ventricular ejection fraction and relative left ventricular end-diastolic volume (portable nuclear VEST monitor) were periodically determined. In both environments, heart rate increased (p less than 0.05), stroke volume decreased (p less than 0.05), and cardiac output remained unchanged with exercise time. In the warmer environment, heart rate was increased (p less than 0.05) and stroke volume tended to be decreased (p less than 0.08), with no difference in cardiac output. In both environments, left ventricular ejection fraction did not change from minute 6 to 60 of exercise, whereas relative left ventricular end-diastolic volume decreased (p less than 0.05) with exercise time. Arterial blood pressure was unchanged from minute 6 to 60 in the warm environment. Arrhythmias were not altered by exercise time or environment, and no subjects had evidence of myocardial ischemia. The data indicate that although heart rate increased and stroke volume and relative left ventricular end-diastolic volume decreased with exercise time, cardiac output and left ventricular ejection fraction remained unchanged in both thermoneutral and warm environments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626506 TI - Mechanisms and dynamics of episodes of progression of 2:1 atrioventricular block in patients with documented two-level conduction disturbances. AB - Twenty episodes of progression of 2:1 atrioventricular (AV) block were identified during incremental atrial stimulation in 7 patients with documented (2-level) block in the AV node and His-Purkinje system. All occurred at cycle lengths shorter than those at which stable 2:1 HV block had been detected. Thirteen episodes were typical since 2:1 increased to 3:1 AV block when an atrio-His (AH) Wenckebach period was completed with an atrial impulse that otherwise would have been conducted. These episodes occurred with dynamic A(M): V(N) ratios similar to those seen at the AV node. Seven atypical episodes were identified (while AH Wenckebach periods were occurring): (1) 2:1 increasing to 3:1 AV block and then to 4:1 AV block resulting from prolonged refractoriness in the His-Purkinje system subsequently followed by concealed conduction in the latter structure; (2) conversion of 3:2 directly into 3:1 AV block due to block of the next-to-last atrial impulse in the His-Purkinje system with completion of AH Wenckebach period with the following atrial impulse; and (3) 4:2 AV block presumably due to supernormal conduction in a transversely dissociated His-Purkinje system. These episodes occurred with A(M): V(N) ratios, which in other structures would have been indicative of different degrees of AV block. In conclusion, progression of 2:1 AV block during documented 2 level conduction disturbances (1) can be explained by mechanisms different than those currently known, and (2) has rich, but different dynamics from those observed exclusively in the AV node and exclusively in the His-Purkinje system. PMID- 1626507 TI - Electrocardiographic abnormalities after radiofrequency catheter ablation of accessory bypass tracts in the Wolff-Parkinson-White syndrome. AB - Repolarization abnormalities on surface electrocardiograms have been described after loss of ventricular preexcitation in some patients with the Wolff-Parkinson White syndrome. Radiofrequency catheter ablation of overt accessory pathways provides a unique opportunity to study this phenomenon. In this study, serial electrocardiograms were obtained before and after radiofrequency ablation of manifest accessory pathways in 19 patients, of concealed accessory pathways in 6 and after radiofrequency atrioventricular nodal modification in 12. Seven patients undergoing manifest right-sided accessory pathway ablation had left superior frontal plane T-wave axis deviations after ablation (-42 +/- 13 degrees). No patient with a manifest left-sided or concealed accessory pathway, or atrioventricular nodal modification had T-wave abnormalities after ablation; however, left anterior fascicular block and incomplete right bundle branch block each occurred in 1 patient with left accessory pathway ablation. Repolarization abnormalities observed after ablation were similar to T-wave abnormalities during the absence of preexcitation before ablation and persisted up to 5 weeks after the procedure. Patients with repolarization abnormalities after ablation had significantly longer preexcited QRS durations than those without such changes, suggesting that the initial contribution of the pathway to ventricular activation is an important determinant of T-wave changes after ablation. The proposed mechanism for repolarization abnormalities after ablation is the phenomenon of T wave "memory." PMID- 1626508 TI - Improved detection of accessory pathways that bridge posterior septal and left posterior regions in the Wolff-Parkinson-White syndrome. AB - To improve the detection of accessory pathways that bridge the posterior septum and left posterior free wall, catheter maps of the coronary sinus from 21 patients (group I) who needed dissection of both these anatomic regions were compared with data from 23 (group II) with pathways confined to the posterior septum and from 9 (group III) with left posterior pathways. A decapolar catheter was used to map the coronary sinus in 0.5 to 1 cm steps. Intraoperative mapping was performed with a 16-electrode band. Catheter maps during atrial pacing and orthodromic supraventricular tachycardia were analyzed for the site of earliest activation and for differences in a new directional measure of conduction time between adjacent mapping sites. The site of earliest activation alone did not distinguish accessory pathways that bridged both anatomic regions, because 14 of 21 patients (66%) in group I would have been misclassified to either group II or III. In contrast, anterograde and retrograde directional conduction times distinguished patients in group I from those in groups II (p less than 0.01 to less than 0.0003) and III (p less than 0.04 to less than 0.0001). A multivariate model that incorporated the observed differences in directional interelectrode conduction times improved the identification of group I patients, with a sensitivity of 87% and a specificity of 90%. The results define new features in activation patterns measurable during catheter mapping that identify accessory pathways that bridge the posterior septum and left posterior free wall. PMID- 1626509 TI - Recordings from the slow zone of reentry during burst pacing versus programmed premature stimulation for initiation of reentrant ventricular tachycardia in patients with coronary artery disease. AB - Programmed premature stimulation and burst pacing were compared for initiation of ventricular tachycardia (VT) in 16 patients with inducible sustained monomorphic VT. In all patients VT could be induced by programmed stimulation with 2 or 3 extrastimuli. On the other hand, initiation of VT by burst pacing was dependent on the length of the train; only 2 to 4 of the 11 trains tested could induce VT in any single patient. Recordings obtained from the slow zone of reentry showed that programmed premature stimulation that induced VT resulted in a critical degree of conduction delay as revealed by lengthening of local fractionated electrograms spanning 70 to 100% of the diastolic interval. Similarly, the last beat of a burst pacing train that induced VT was always followed by a similar degree of local conduction delay, whereas trains that failed to induce VT were followed by a lesser delay. It is concluded that although programmed stimulation with up to 3 extrastimuli was consistently successful in inducing VT, burst pacing succeeded in only 26% of the trials and was dependent on the length of the train, which varied from one patient to the other. Similar to what was shown previously in the experimental model of reentrant VT, burst pacing could initiate, conceal, terminate, and reinitiate reentry depending on the length of the train. PMID- 1626510 TI - Radiation exposure to patients and medical personnel during radiofrequency catheter ablation for supraventricular tachycardia. AB - Radiofrequency catheter ablation is an effective alternative to medical therapy for patients with supraventricular arrhythmias. The purpose of this study was to determine the risks to the patient and to medical personnel due to radiation exposure from fluoroscopy during radiofrequency ablation of supraventricular tachycardia. One hundred eight consecutive patients with Wolff-Parkinson-White syndrome or atrioventricular nodal reentry who underwent the ablation procedure were studied. The ablation procedure was successful in 95% of the patients studied. Preexcitation or supraventricular tachycardia recurred in 5% of the patients during a mean follow-up of 9 +/- 4 months. The mean fluoroscopy time was 50 +/- 31 minutes. An anthropomorphic radiologic phantom was used to determine organ exposure and the effective dose equivalents for the patient and medical personnel. The patient's effective dose equivalent during a representative ablation procedure was 1.7 rems, which is comparable to other invasive cardiovascular procedures. The risk of inducing a fatal cancer from this exposure is 1 chance in 745, which is 1% of the spontaneous risk. The risk of a serious birth defect is 1 chance in 80,000, which is 0.1% of the current incidence of serious birth defects in the United States. The cardiologist who receives the highest exposure among medical personnel, would incur 1.8 mrems per case or 450 mrems per year if 250 procedures were performed. This exposure is 9% of the recommended annual limit. These results demonstrate the efficacy of radiofrequency energy ablation of supraventricular tachycardia and confirm that radiation exposure to patients and medical personnel is within established guidelines. PMID- 1626511 TI - Baroreceptor-mediated release of vasopressin in patients with chronic congestive heart failure and defective sympathetic responsiveness. AB - In patients with congestive heart failure (CHF), overactivity of the sympathetic nervous system may be accompanied by an impairment of the baroreflex control mechanism. To evaluate the reflex responses of the sympathetic nervous system, the renin-angiotensin system and vasopressin release to baroreceptor unloading, 38 patients with left ventricular dysfunction were studied. Hemodynamic data, and plasma norepinephrine, renin activity and vasopressin concentrations were measured before and 60 minutes after administration of high-dose hydralazine (0.4 mg/kg intravenously). On the basis of blood pressure response to vasodilator administration, patients were divided arbitrarily into those with a decrease in mean arterial blood pressure greater than or equal to 15 mm Hg (group A; n = 12) and those with a decrease less than 15 mm Hg (group B; n = 26) compared with control values. In response to hydralazine, heart rate decreased in group A from 100 to 92 beats/min (p less than 0.001) and increased in group B from 90 to 96 beats/min (p less than 0.05). In group A, hemodynamic changes induced by hydralazine were accompanied by a decrease in plasma norepinephrine from 822 to 518 pg/ml (p less than 0.01) and an increase in plasma vasopressin from 8.4 to 45.2 pg/ml (p less than 0.001). In group B, plasma norepinephrine and vasopressin did not change significantly (407 vs 447, and 8.4 vs 8.3 pg/ml, respectively). Plasma renin activity remained unchanged in group A and increased in group B (p less than 0.001). The data show that baroreceptor-mediated release of vasopressin is not impaired in patients with CHF and a defective sympathetic reflex control mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626512 TI - Rate of progression of valvular aortic stenosis in adults. AB - Until recently the hemodynamic severity of valvular aortic stenosis (AS) was evaluated only by cardiac catheterization. Now, Doppler echocardiography allows a noninvasive and accurate assessment of AS severity and can be used to study its progression with time. The progression of AS was assessed during a follow-up period of 6 to 45 months (mean 18) by serial Doppler examinations in 45 adult patients (21 men and 24 women, mean age 72 +/- 10 years) with isolated AS. The following parameters were serially measured: left ventricular outflow tract diameter and velocity by pulsed Doppler, peak velocity of aortic flow by continuous-wave Doppler, to calculate peak gradient by the modified Bernoulli equation, and aortic valvular area by the continuity equation. At the initial observation, 13 of 45 patients (29%) were symptomatic (1 angina, 1 syncope and 11 dyspnea); during follow-up, 25 (55%) developed new symptoms or worsening of the previous ones (5 angina, 3 syncope and 17 dyspnea); 11 underwent aortic valve replacement and 3 died from cardiac events. Baseline peak velocity and gradient ranged between 2.5 and 6.6 m/s, and 25 and 174 mm Hg, respectively; aortic area ranged between 0.35 and 1.6 cm2. With time, mean peak velocity and gradient increased significantly from 4 +/- 0.7 to 4.7 +/- 0.8 m/s (p less than 0.01), and 64 +/- 30 to 88 +/- 30 mm Hg (p less than 0.01), respectively. A concomitant reduction in mean aortic area occurred (0.75 +/- 0.3 to 0.6 +/- 0.15 cm2; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626513 TI - Comparison of cardiac findings in patients with mitral valve prolapse who die suddenly to those who have congestive heart failure from mitral regurgitation and to those with fatal noncardiac conditions. AB - Sudden death occurs in a small but important subset of patients with mitral valve prolapse (MVP). Clinical criteria for identifying patients at risk for sudden death have been elusive. To determine if certain morphologic characteristics were present in hearts from patients with sudden cardiac death and MVP, autopsy hearts from persons with sudden death and isolated MVP who were previously asymptomatic or had a history of cardiac arrhythmias (n = 27) were compared with (1) hearts from patients with congestive heart failure (CHF) and mitral regurgitation (MR) secondary to MVP (n = 14), and (2) hearts from persons dying from non-cardiac causes in which MVP was an incidental finding (n = 19). Patients who died suddenly were younger than both patients with MR/CHF and incidental cases (37 +/- 10 vs 65 +/- 16 and 58 +/- 21 years, respectively, p less than 0.001). Mitral valve annular circumference, anterior and posterior mitral valve leaflet lengths, posterior mitral valve thickness, and presence and extent of endocardial plaque were greater in hearts from patients with sudden death than hearts from those with incidental MVP. Hearts from patients with MR/CHF weighed significantly more, had greater left and right atrial cavity sizes and left ventricular cavity diameter than hearts from both sudden death and incidental cases. PMID- 1626514 TI - Hemodynamic evaluation by Doppler echocardiography of small (less than or equal to 21 mm) prostheses and bioprostheses in the aortic valve position. AB - To assess resting hemodynamics of an unselected group of patients with prostheses or bioprostheses sized less than or equal to 21 mm implanted into the aortic valve position during a 7-year period, 46 of 50 eligible patients were examined by Doppler echocardiography. The valves were Carpentier-Edwards (CE) supraannular 21 mm (n = 8), Medtronic-Hall (MH) 20 mm (n = 8) and 21 mm (n = 21), and the rest (n = 9) were other valves with only 1 to 3 patients in each group. Gradients, valve areas and dimensionless obstruction indexes (ratio of subvalvular/valvular velocities and velocity time integrals) were compared. By analysis of variance, gradients did not differ significantly between the CE supraannular 21 mm, the MH 20 and 21 mm prostheses (peak/mean 25 +/- 8/14 +/- 5, 31 +/- 13/16 +/- 6 and 25 +/- 10/13 +/- 5 mm Hg; p = not significant). Only 2 patients had a mean gradient greater than 25 mm Hg. The valve area was slightly larger for the MH 21 mm group compared with the CE supraannular 21 mm group (1.34 +/- 0.15 vs 1.16 +/- 0.14 cm2, p less than 0.05). The dimensionless obstruction indexes did not differ (CE supraannular 21 mm 0.36 +/- 0.07/0.40 +/- 0.07 (velocities/velocity time integrals), MH 20 mm 0.40 +/- 0.12/0.47 +/- 0.12, MH 21 mm 0.38 +/- 0.05/0.44 +/- 0.06; p = not significant).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626515 TI - Usefulness of transesophageal echocardiography in evaluation of paracardiac neoplastic masses. AB - Mediastinal paracardiac tumors may cause both cardiovascular complications and problems in differential diagnosis of cardiac diseases. Transesophageal echocardiography (TEE) may give an additional new window to mediastinal neoplasms, but only a few studies have been reported. TEE was performed in 70 patients with paracardiac neoplastic masses. The procedure was indicated to solve particular clinical problems in 20 patients, and as a prospective study on 50 unselected patients with mediastinal neoplasms. Twenty-three patients underwent follow-up studies; a total of 101 echocardiograms were recorded. The procedure was tolerated well or very well by most patients, and provided additional anatomic or hemodynamic data in every patient in group a and in 45 of 50 in group b. The additional data were relevant for clinical management in 14 of 20 patients in group a, and in 3 of 45 in group b. Based on the results of this study, TEE is useful in association with other radiologic techniques in patients with paracardiac neoplasms. As an imaging technique, it may represent a reliable alternative to computed tomography whenever the latter is not feasible. PMID- 1626516 TI - Safety of intravenous high-dose dipyridamole echocardiography. The Echo Persantine International Cooperative Study Group. AB - Clinical data on 10,451 high-dose (up to 0.84 mg/kg over 10 minutes) dipyridamole echocardiography tests (DET) performed in 9,122 patients were prospectively collected from 33 echocardiographic laboratories, each contributing greater than 100 tests. All patients were studied for documented or suspected coronary artery disease (1,117 early [less than 18 days] after acute myocardial infarction and 293 had unstable angina). Significant side effects including major adverse reactions and minor but limiting side effects occurred in 113 patients (1.2%). Major adverse reactions occurred in 7 cases (0.07%). In 6 of these cases, adverse reactions were associated with echocardiographically assessed ischemia and included 1 prolonged cardiac asystole (complicated by acute myocardial infarction and coma, with death after 23 days), 1 short-lasting cardiac asystole, 2 myocardial infarctions, 1 pulmonary edema and 1 sustained ventricular tachycardia. In all 6 cases, the cardiologist-echocardiographer performing the study had a limited experience (less than 100 tests) with DET, and at off-line reading in 5 cases, the obvious echo-positivity preceded the onset of complications by 1 to 5 minutes. The only ischemia-independent major side effect was a short-lasting cardiac asystole that was reversed by aminophylline and atropine. Significant side effects associated with echocardiographically assessed ischemia occurred in 89 additional cases (21 with and 68 without concomitant echocardiographically assessed myocardial ischemia). The most frequent of these side effects was hypotension or bradycardia, or both, which occurred in 40 patients with negative and 6 with positive DET. In all cases, side effects promptly subsided after aminophylline. In 1,857 cases, the high dose was not given for echo-positivity before the eighth minute.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626517 TI - Left ventricular mass quantitation using single-phase cardiac magnetic resonance imaging. AB - Magnetic resonance imaging (MRI) has been used to measure left ventricular (LV) mass in animals with superior accuracy. However, its use in cardiac patients has been limited by the long total scan times necessitated by imaging the heart at end-diastole at each of 8 to 10 slice locations. Recent canine studies showed that LV mass may be determined accurately, with considerable timesavings, by use of sequential images throughout the cardiac cycle (single-phase MRI). Twenty normal subjects underwent spin-echo MRI to determine the relationship between LV mass computed from single-phase MRI and results obtained from the more time consuming end-diastolic MRI (which was used as the reference standard for this study). The left ventricle was spanned with 2 interleaved series of 5 short-axis 1 cm thick slices. 5 images, evenly spaced throughout the cardiac cycle, were obtained at each slice location in all subjects. LV mass ranged from 86 to 198 g. Although end-diastolic LV mass exceeded single-phase results by an average of 5 g (p less than 0.002), there was a close correlation between the 2 (slope = 0.99; r = 0.96). Although LV mass derived from end-diastolic images exceeded single-phase results, this difference is unlikely to be clinically significant and is small compared with the standard error of echocardiographic methods. Furthermore, when the order in which single-phase images were selected was reversed, there was improved agreement with end-diastolic MRI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626518 TI - Morphologic findings in explanted Mitroflow pericardial bioprosthetic valves. PMID- 1626519 TI - Electrocardiographic abnormalities in mitral valve prolapse. PMID- 1626520 TI - Balloon cutting. PMID- 1626522 TI - More on fast foods and quick plaques. PMID- 1626521 TI - Does enflurane effect ventricular tachycardia? PMID- 1626523 TI - A long-term comparison of nonextraction and premolar extraction edgewise therapy in "borderline" Class II patients. AB - The long-term effects of extraction and nonextraction edgewise treatments were compared in 63 patients with Class II, Division 1 malocclusions who were identified by discriminant analysis as being equally susceptible to the two strategies. A lateral cephalogram, study models, and a self-evaluation of the esthetic impact of treatment were obtained from each of the 33 extraction and 30 nonextraction subjects. The average posttreatment interval was 14.5 years. Although the two strategies produced significant, long-lived differences in the convexity of the profile and the protrusion of the dentition (the nonextraction patients were about 2 mm "fuller"), half of the nonextraction patients and three fourths of the extraction patients ultimately presented with less than 3.5 mm of lower incisor irregularity. The two groups showed an essentially identical pattern of posttreatment relapse/settling that was related more to the differential growth of the jaws than to the posttreatment position and orientation of the denture. Because in the end the various tooth movements tended to cancel one another, excess mandibular growth was also the most important net contributor to the molar and overjet corrections. In the process, both groups showed a marked forward displacement of the mandible, both at the chin and at the condyle. Finally, although it is probable that most of the present sample would today be treated by expansion, the 30 patients who actually received this presumably correct treatment rated their appearance no more highly than did the extraction subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626524 TI - Superelastic wires. PMID- 1626525 TI - Prediction of cooperation in orthodontic treatment. AB - A prospective study of patient cooperation with orthodontic treatment was conducted on 100 adolescent patients. Patient, parent, and orthodontist questionnaires were used at three stages of orthodontic treatment. The first was used at the initiation of treatment and the latter two at 6-month intervals. Psychosocial measures from investigators reported in orthodontic patient cooperation literature were screened for use in the present study. These measures included attitudes toward treatment, social desirability, need for approval, and need for achievement. None of the variables selected for this investigation adequately predicted cooperation of a patient in orthodontic treatment. The stepwise regression procedures indicated that inclusion of all variables accounted for 40% of the variability. Variables assessing the orthodontist's perception of orthodontist-patient relationship had the strongest association with patient compliance. PMID- 1626526 TI - Comment on mandibular growth. PMID- 1626527 TI - Special TMJ issue comment. PMID- 1626528 TI - More comments on the special TMJ issue. PMID- 1626529 TI - Occlusal contact changes after the active phase of orthodontic treatment. AB - Occlusal contacts in maximum intercuspidation were recorded at the end of active orthodontic treatment and 3 months into the retention period. Hawley retainer, tooth positioner, and nontreated normal occlusion groups of 10 subjects were examined for change in the number and location of occlusal contacts. Soft silicone-base impression materials were used to make interocclusal registrations. The contacts were then transferred onto the study models, and standard photographs of each model were taken. To determine any locational changes, superimposition of the first registration photograph on the second one was done. Significant difference in the number of total contacts between the treated groups and the control sample was recorded at both time periods. Use of a tooth positioner as a retainer did not show any additional gain of contacts in the positioner group when compared with the Hawley retainer group. No significant change in the location of contacts occurred during the period of observation. PMID- 1626530 TI - The duration of orthodontic treatment. AB - Characteristics of the patient, the treatment plan, and the practitioner's office were examined to evaluate causes for variation in the duration of orthodontic treatment. From six offices 118 patients were evaluated. All patients were treated in a single phase with fixed appliances. Appliances were worn for an average of 23.1 months. The mean duration for offices ranged from 19.4 to 27.9 months. Thirty-eight percent of the patients had extractions, and 32% wore headgear. Fifty percent of the variation in treatment duration among patients was explained by a five-step multiple regression equation. The variables entering this equation were (1) number of extracted premolars, (2) number of broken appointments, (3) pretreatment mandibular plane angle, (4) pretreatment ANB angle, and (5) pretreatment Salzmann Index. Observations within each office suggested that the time spent by individual clinicians in detailed finishing, which would not be detected by measures such as the Salzmann Index, was an important source of unexplained variation in treatment duration. PMID- 1626531 TI - A multivariate analysis of the relations between craniofacial structure and occlusion with DiPaolo's quadrilateral measures. AB - This study examined the relations between craniofacial structure and occlusion with clinically oriented skeletal measures consistent with Enlow's counterpart principle and a combination of univariate and multivariate statistics. The pretreatment lateral cephalograms and dental casts of 59 white adolescents with natural skeletal and occlusal development were selected to provide a random sampling of various malocclusions. Craniofacial structure was described with DiPaolo's quadrilateral measures. The relations between craniofacial structure and occlusion were analyzed with simple correlation analysis, stepwise multiple regression, and stepwise discriminant analysis. Intratester and intertester reliability were established, and a lack of sexual dimorphism was demonstrated. Three types of relations were identified: anteroposterior relations, vertical relations, and coordinations. A strong association was found between the variation in the anteroposterior measures and the variation in sagittal occlusion. A more modest association was found between the variation in the vertical measures and the variation in vertical occlusion. A combined skeletal measure composed of the variable pair mandibular plane angle and the ratio of anterior lower facial height to anterior upper facial height was found to explain the greatest percent of the variance in vertical occlusion. Several coordinations were found which, when taken together, described an overall pattern of associations. PMID- 1626532 TI - Variations in bracket placement in the preadjusted orthodontic appliance. AB - This study was conducted to determine the accuracy of bracket placement with the direct bonded technique. Ten orthodontic faculty members bonded a preadjusted orthodontic appliance on models of five cases of malocclusion in a simulated clinical situation (mannequin). A total of 50 sets of models served as the population of the study. Photographs of the models were measured to determine vertical and angular discrepancies in position between adjacent bracket pairs from a constructed reference line. Variations are evaluated with respect to the classification of malocclusion, specific tooth type, and intra/inter operator differences. A mean of 0.34 mm for the vertical discrepancies and a mean of 5.54 degrees for the angular discrepancies are found in placement of the orthodontic brackets. PMID- 1626533 TI - Compliance with infection control procedures among California orthodontists. AB - We conducted a survey of a random sample of California orthodontists and of general dentists to compare their infection control procedures. Questionnaires were returned by 124 orthodontists (56% response rate) and 126 general dentists (61% response rate). Eighteen questions were asked covering practice profile, perception of risk from hepatitis B virus (HBV) and human immunodeficiency virus (HIV), exposure to blood, barrier protection used, and sterilization and disinfection procedures. Gloves always were worn by 80% of the orthodontists sampled, 63% always wore glasses, and 59% changed gloves between patients. Orthodontists sterilized their instruments 66% of the time and pliers 49% of the time. Compared with general dentists, orthodontists' perception of risk, use of barrier protection, and sterilization and disinfection procedures were lower in all areas. Our data suggest that poorer performance may be because orthodontists: (1) perceive their younger population of patients at less risk for HBV and HIV; (2) treat 2.5 times as many patients, which increases the costs of infection control; (3) do not use invasive procedures; and (4) perceive that glove use decreases dexterity. Orthodontists should follow the American Dental Association/Council on Dental Therapeutics infection control guidelines for universal precautions. To meet these guidelines, orthodontists still need improvement in all aspects of their infection control procedures. PMID- 1626534 TI - Improving the facial profile of a girl born with a right unilateral cleft lip and palate. PMID- 1626535 TI - Alveolar bone: the production of eruption. PMID- 1626536 TI - Exposure control plan. PMID- 1626537 TI - The changing pattern of human immunodeficiency virus type 1 infection in intravenous drug users. Results of a six-year seroprevalence study in Palermo, Italy. AB - A cross-sectional seroepidemiologic study was carried out between 1985 and 1990 in 1,567 heterosexual intravenous drug users who had been seen at the AIDS Regional Reference Center in Palermo, Italy, to evaluate the rate of human immunodeficiency virus type 1 (HIV-1) seroprevalence in this group and its long term trend. Sixty serum samples collected from drug users in 1980 and 1983, before the founding of the Center (1985), were tested as well. Some demographic and behavioral risk factors were studied in a subgroup of intravenous drug users enrolled in 1985, 1987, and 1990 for their possible association with HIV-1. These factors were also studied in relation to hepatitis B virus infection, since both viruses share the same modes of spread. These drug users had a higher prevalence of markers for hepatitis B virus than of HIV-1 antibodies, and the prevalence rates in sera collected declined over time for both infections. The presence of both antibodies to HIV-1 and markers for hepatitis B virus was independently associated with the age of the drug user, the duration of drug use, and the year of serum collection. Antibodies to HIV-1 were observed more frequently in females than in males. No relation was found between education or employment status and the presence of HIV-1 antibodies or hepatitis B virus markers. Although new HIV-1 infections still occur, the decline in seroprevalence observed at the end of the 1980s might be related to modifications in social behavior among newer drug users, partial exhaustion of the susceptible population, and increasing risk awareness in more experienced users. PMID- 1626538 TI - Risk of congenital malformations associated with proximity to hazardous waste sites. AB - Concern about environmental pollutants has increased; however, it remains unclear whether chronic exposures to toxic chemicals in the environment occur at doses sufficient to produce adverse health effects in humans. To date, community studies have not adequately addressed this question. In this study, the authors linked two existing data bases of the New York State Department of Health to evaluate the relation between congenital malformations and residential proximity to hazardous waste sites in New York State. A total of 9,313 newborns with congenital malformations and 17,802 healthy controls living in proximity to 590 hazardous waste sites in 1983 and 1984 were evaluated. After the authors controlled for several possible confounding factors, results indicated that maternal proximity to hazardous waste sites may carry a small additional risk of bearing children with congenital malformations (odds ratio (OR) = 1.12, 95% confidence interval (Cl) 1.06-1.18). Higher malformation rates were associated with both a higher exposure risk (no exposure risk: OR = 1.00; low exposure risk: OR = 1.09, 95% Cl 1.04-1.15; high exposure risk: OR = 1.63, 95% Cl 1.34-1.99) and documentation of off-site chemical leaks (not exposed: OR = 1.00; exposed, but no leaks at site: OR = 1.08, 95% Cl 1.02-1.15; exposed, and leaks found at site: OR = 1.17, 95% Cl 1.08-1.27). The increased rates detected may be important in terms of their public health implications. Further research is necessary to strengthen causal inferences regarding the teratogenicity, of waste site exposure. PMID- 1626539 TI - Fertility of male workers exposed to cadmium, lead, or manganese. AB - The effect of exposure to cadmium, lead, or manganese on male reproductive function was examined in 1988-1989 in Belgian blue-collar workers. The workers were exposed to cadmium in two smelters (n = 83; geometric mean urinary cadmium level = 6.94 micrograms/g of creatinine; mean duration of exposure = 24 years), to lead in a battery factory (n = 74; mean blood lead level = 46.3 micrograms/dl; mean duration of exposure = 10.7 years), or to manganese (manganese dioxide) in a dry alkaline battery plant (n = 70; median atmospheric concentration of total manganese dust = 0.71 mg/m3; mean duration of exposure = 6.2 years). Fertility in these workers and in an unexposed population (n = 138) was assessed by examining the birth experiences of their wives through a logistic regression model. The probability of a live birth was not different between the unexposed workers and the cadmium- or manganese-exposed workers before or after the onset of exposure. While the fertility of the lead-exposed workers was somewhat greater than that of the unexposed before the onset of exposure, a significant decrease in fertility was observed during the period of exposure to the metal (odds ratio = 0.65, 95% confidence interval 0.43-0.98). PMID- 1626541 TI - Short- and long-term association of serum cholesterol with mortality. The 25-year follow-up of the Finnish cohorts of the seven countries study. AB - The association of serum cholesterol with cause-specific and all-cause mortality was assessed in a cohort of 1,426 men aged 40-59 years who were free of clinically evident heart disease at baseline (1959). A total of 748 deaths (53 percent of the participants) occurred during the 25-year follow-up period. Men with high serum cholesterol levels at baseline had high mortality due to coronary heart disease during both the early and later parts of the follow-up period. In contrast, the association of serum cholesterol with mortality due to causes other than coronary heart disease changed during follow-up (interaction of cholesterol with follow-up period: p = 0.004). During the first 10 years of follow-up, despite their high coronary mortality, men with high cholesterol levels had lower all-cause mortality (age-adjusted relative risk = 0.71 for serum cholesterol above 5.79 mmol/liter vs. below 5.80 mmol/liter; p = 0.03) because of their low cancer mortality (relative risk = 0.55, p = 0.03) and residual mortality (relative risk = 0.49, p less than 0.01). During the last 15 years of follow-up, cholesterol at baseline was no longer associated with mortality due to causes other than coronary heart disease, and consequently, because of their high coronary mortality, men with high cholesterol levels also had higher all-cause mortality (relative risk = 1.22, p = 0.05). The results suggest that to fully analyze the association of serum cholesterol with all-cause mortality, the follow up period should be sufficiently long--possibly more than 10 years--and the possibility of a change in the direction of the association studied should always be considered. PMID- 1626540 TI - Sex hormones and postmenopausal breast cancer: a prospective study in an adult community. AB - Few studies have examined the role of endogenous sex hormones in breast cancer, and to the authors' knowledge, only two have done so prospectively. The authors report here the results of a prospective study based on an available bank of previously analyzed plasma collected in 1972-1974 from 442 women aged 50-79 years in Rancho Bernardo, California. These women were followed for 12-15 years, during which time 42 cases of breast cancer were identified: 15 incident cases diagnosed 1 year or more after baseline, 18 prevalent cases diagnosed earlier than 1 year after baseline, and 9 cases with unknown dates of onset. No apparent trends in plasma levels of sex hormones or sex hormone-binding globulin and incidence or prevalence of breast cancer were observed. Mean crude and age-adjusted plasma hormone levels at baseline (in pg/ml) for incident cases, total cases, and noncases, respectively, were: androstenedione: 647, 638 +/- 328 (standard deviation); 626, 620 +/- 245; and 664, 664 +/- 291; testosterone: 254, 258 +/- 120; 238, 241 +/- 153; and 262, 261 +/- 143; estrone: 37, 38 +/- 18; 35, 35 +/- 15; and 37, 37 +/- 17, and estradiol: 13, 13 +/- 7; 15, 15 +/- 8; and 15, 15 +/- 9. For sex hormone-binding globulin, mean crude and age-adjusted levels at baseline (nM) were 35 and 36 +/- 33 for incident cases; 31 and 31 +/- 25 for total cases; and 29 and 29 +/- 21 for noncases. Cox proportional hazards multiple regression showed no associations with breast cancer after simultaneous adjustment for age, body mass index, and cigarette smoking. PMID- 1626542 TI - The FINMONICA Stroke Register. Community-based stroke registration and analysis of stroke incidence in Finland, 1983-1985. AB - In the early 1980s, a standardized community-based stroke register was started in three geographic areas in Finland: North Karelia and Kuopio in eastern Finland and Turku/Loimaa in southwestern Finland. The results from the first 3 years, 1983-1985, confirmed the high incidence of stroke in Finland. The incidence of stroke was higher in eastern Finland than in the southwestern part of the country. The age-standardized annual incidence among men aged 25-74 years varied from 206 per 100,000 population in southwestern Finland to 322 per 100,000 population in the province of Kuopio in eastern Finland. Among women aged 25-74, incidence was 119 and 187 per 100,000 population in these two areas, respectively. The age-standardized male:female ratio in incidence was 1.7, slightly higher than that previously reported in Finland. Out of 3,574 stroke events registered, 78% were first events without a history of previous stroke. People aged 65-74 years accounted for 45% of all events among men and 62% of all events among women. The authors' experience shows that the geographic variation in stroke incidence and attack rates is difficult to assess even within a country with a relatively uniform health care system. Rigorous standardization and quality control is needed for the assessment of long-term trends; this is the primary goal of the FINMONICA Stroke Register. The findings of this study suggest that the incidence of stroke is still high in Finland, although mortality from stroke has steeply declined during the past 15-20 years. The number of stroke survivors in Finland may actually be increasing. Since the occurrence of stroke is high in Finland as compared with other countries, intensified primary and secondary prevention measures are needed to reduce it. PMID- 1626544 TI - Alcohol consumption regression models for distinguishing between beverage type effects and beverage preference effects. AB - In relating health outcomes to alcohol consumption, several investigators have evaluated differences among beverage types, but there is no consistency with respect to models used for this purpose. Furthermore, beverage type effects and beverage preference effects have not been evaluated simultaneously. In this report, the authors propose regression models which permit the simultaneous evaluation of beverage type (congener dose response) effects and beverage preference (sociobehavioral) effects. The presence of sociobehavioral effects can be established even if the variables responsible for them have not been measured or identified. The models are applied to a data set from 589 women who participated in an oral contraceptive study at the Johns Hopkins University (Baltimore, Maryland) in 1988-1989. PMID- 1626543 TI - Influence of body fat and its regional localization on risk factors for atherosclerosis in young men. AB - A study was carried out in 1988 in Verona, Italy, to examine the relation of body fat and its localization to several risk factors for atherosclerosis in young men. Total body fat (bioelectrical impedance), waist and hip circumferences, and waist/hip circumference ratio were measured in 1,293 18-year-old men. Fasting serum levels of total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, and insulin, as well as systolic and diastolic blood pressure, were also measured. Significant differences were found in all metabolic and hemodynamic variables among quartiles of total body fat. Most of these differences remained significant after the authors controlled for the independent effect of fat localization and behavioral factors such as smoking, alcohol intake, and physical activity. Triglycerides, insulin, and blood pressure were significantly different among quartiles of waist/hip ratio, but these differences disappeared after the authors controlled for the independent effect of total body fat. These results indicate that in young men, irrespective of its regional localization, an excess of body fat is associated with a poor profile of risk for atherosclerosis. On the other hand, the prevalent localization of fat in the central part of the body is not independently associated with any risk factor. PMID- 1626545 TI - Nonlinear modeling of alcohol consumption for analysis of beverage type effects and beverage preference effects. AB - In a previous report (Kimball and Friedman, Am J Epidemiol, 1992;135:1279-86), linear models for relating health outcomes to alcohol consumption were proposed for differentiating between beverage type effects and beverage preference effects. The models were applied to data relating serum high density lipoprotein cholesterol to alcohol consumption. In this report, those models are extended to the nonlinear case and are applied to data from the 1982 Maryland Hypertension Survey relating systolic blood pressure to alcohol consumption. PMID- 1626546 TI - Epidemiologic mapping using the "kriging" method: application to an influenza like illness epidemic in France. AB - This paper presents the application of a technique from the earth sciences, the "kriging" method, to the field of geographic epidemiology. Both the principles of the method and the basic equations are given. A key advantage of the method is that it relies on an analysis of the spatial variability of the data and allows the representation of the variable under study as a continuous process throughout a country. Application of the kriging method to the geographic distribution of an epidemic of influenza-like illness in France is discussed. PMID- 1626547 TI - Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. AB - Meta-analysis often requires pooling of correlated estimates to compute regression slopes (trends) across different exposure or treatment levels. The authors propose two methods that account for the correlations but require only the summary estimates and marginal data from the studies. These methods provide more efficient estimates of regression slope, more accurate variance estimates, and more valid heterogeneity tests than those previously available. One method also allows estimation of nonlinear trend components, such as quadratic effects. The authors illustrate these methods in a meta-analysis of alcohol use and breast cancer. PMID- 1626548 TI - Re: "A statistical method for evaluating suicide clusters and implementing cluster surveillance". PMID- 1626549 TI - Re: "Case-control studies of environmental influences in diseases with genetic determinants, with an application to Alzheimer's disease". PMID- 1626550 TI - Re: "Birth defects among offspring of firemen". PMID- 1626551 TI - The future of the end-stage renal disease program. AB - The rapidly changing health care environment in the United States will affect the future of nephrology in several areas. Reductions in Medicare spending will affect graduate medical education, physician payments, and, eventually, payments for medical supplies and therapeutic agents. The resource-based relative value system (RBRVS) developed by the Health Care Financing Administration (HCFA) will be implemented over the next 4 years, and it is likely that similar plans will be adopted by other insurance carriers. Under this system, payments for the procedure of dialysis will be substantially reduced--decreases in Medicare reimbursement will range from approximately 30% to 60% depending on geographic location and current charges. However, the current economic pressures may have a beneficial effect on the practice of nephrology by providing an incentive to develop standardized practice guidelines that will eliminate wide variations in practices and minimize unfounded litigation. In the near future, attention must also focus on the training of nephrology fellows; ideas for future directions are presented. PMID- 1626552 TI - Quality of life and hematocrit level. AB - As the anemia that accompanies chronic renal failure (CRF) is successfully treated with recombinant human erythropoietin (epoetin), striking improvements in overall quality of life have been noted in several clinical studies of patients receiving chronic hemodialysis. A review of available clinical data has shown that, following epoetin therapy, peak oxygen consumption, a principal indicator of exercise ability, increased by approximately 50% as the hematocrit level increased. Following epoetin therapy in pediatric patients with end-stage renal disease (ESRD), the ventilatory anaerobic threshold (VAT) increased significantly and correlated well with increases in hemoglobin concentrations. Increased exercise capacity associated with the reversal of anemia appeared to positively effect many quality-of-life parameters. Analysis of questionnaires incorporating both subjective and objective quality-of-life indicators showed significant improvements between baseline and follow-up periods. Many patients experienced relief from some of the debilitating symptoms of anemia and many had significantly improved functional ability. Higher activity and energy levels were reflected in enhanced emotional and social well-being, with improvements noted in appetite, sleeping behavior, and sexual function. There was no change in the employment status of most patients. The extent of improvement in overall quality of life may be a function of the baseline level of impairment and the potential for reversal. However, baseline capabilities at rest may not be appropriate for physiologic studies. PMID- 1626553 TI - Epoetin and cognitive function. AB - The uremia of chronic renal failure (CRF) can alter brain electrophysiology and cognitive function, even in the well-dialyzed patient. The effect of uremia on brain function can be assessed by electrophysiologic techniques such as electroencephalogram (EEG), sensory-evoked potentials (EPs), and cognitive event related potentials (ERPs), and through a series of neuropsychologic tests. Five tests have been used clinically to measure the speed and efficiency of cognitive functioning and include the following: Number Cancellation, Trailmaking Test, Symbol Digit Modalities Test, Rey Auditory Verbal Learning Test, and Controlled Oral Word Association Test. Test performance by patients with CRF is often below that of healthy controls. Auditory ERPs, a sensitive indicator of subtle changes in central nervous system (CNS) function in uremia, result in the generation of a P300 component wave that varies in amplitude and latency with patient variables such as attention and effort. Although dialysis tends to normalize P300 latencies, the waves remain somewhat prolonged in most patients. The anemia often observed in patients receiving chronic dialysis appears to aggravate uremic encephalopathy. This effect can be reversed when anemia is corrected following administration of recombinant human erythropoietin (epoetin). Improvement in P300 amplitudes, and, in some cases, decreases in P300 latencies correlated well with epoetin-induced increases in hematocrit levels. With the correction of anemia, that component of brain dysfunction not attributable to retention of uremic toxins can largely be reversed. PMID- 1626554 TI - The end-stage renal disease program: trends over the past 18 years. AB - Data from the Michigan Kidney Registry and the US Renal Data System (USRDS) show that the number of patients receiving treatment for end-stage renal disease (ESRD) increased sevenfold following the introduction of Medicare coverage for ESRD in 1973. The number of new patients added per year has also increased dramatically--approximately fourfold. Initial selection criteria for acceptance into the ESRD Program included age less than 65 years and absence of systemic diseases such as diabetes. During the past 18 years, the gradual acceptance of older patients and of diabetic patients has led to an increase in the median age of new patients from 46 to 61 years and a 12-fold increase in the incidence of treatment in patients with ESRD due to diabetes. Given the broad acceptance of sicker and older patients, withdrawal from dialysis has become a consideration when dialysis no longer benefits the patient. Treatment modalities have also changed, and increasing numbers of patients undergo successful renal transplantation or receive continuous ambulatory peritoneal dialysis (CAPD). During the 1980s, hemodialysis treatment times and dialysis staffs decreased; however, several improvements in the care of patients on dialysis occurred during this period. PMID- 1626555 TI - Impact of reimbursement regulations on patient management. AB - The Medicare End-Stage Renal Disease (ESRD) Program has saved the lives of thousands of patients with chronic renal failure; however, the absolute cost of the program has steadily increased since its inception in 1972 and quickly exceeded all budget estimates, although the actual cost per patient has increased only 69%, which is less than half the inflation rate. Cost-containment efforts have resulted in progressive reductions in reimbursement provided by Medicare to both physicians and dialysis centers. The reimbursement amount per dialysis treatment--the largest component of ESRD expenditures--has actually decreased from $138 in 1974 to approximately $54 in 1991 when measured in constant dollars. It is likely that these reimbursement restrictions have negatively impacted the level of patient care; both mortality and morbidity rates in patients receiving chronic dialysis are increasing in the United States. This is a significant cause for concern, particularly as the mortality rates in other industrialized countries began much lower than the US rate and have continued to decline despite adding older and presumably sicker patients. Although the mortality rate may be affected by factors such as broader patient acceptance criteria, particularly the inclusion of older patients and those with serious comorbid conditions, and by an increase in transplantation rates, there is concern that a trend toward shorter dialysis times may, perhaps, result in inadequate dialysis treatment. PMID- 1626556 TI - Hereditary amyloidosis and cardiomyopathy. PMID- 1626557 TI - Hepatotoxicity associated with sustained-release niacin. AB - Niacin (nicotinic acid) is a widely used agent in the treatment of hyperlipidemias characterized by elevated low-density lipoprotein and very-low density lipoprotein. The tendency of the conventional crystalline niacin to cause flushing has limited its use in many patients. Sustained-release (SR) niacin preparations are increasingly utilized due to a lower incidence of flushing and convenient dosing frequency. Although gastrointestinal and hepatotoxic side effects are common to both formulations, they are more frequent and occasionally more severe with the SR preparations. We describe a patient who developed an acute illness characterized by hypothermia, hypotension, metabolic acidosis, and severe hepatic dysfunction 2 days after substitution of an SR preparation for a previously well-tolerated crystalline niacin. PMID- 1626558 TI - Purulent tuberculous pericarditis with cardiac tamponade. PMID- 1626559 TI - Gas-forming soft tissue abscess caused by Streptococcus pneumoniae. PMID- 1626560 TI - Effective treatment of cerebral toxoplasmosis with doxycycline. PMID- 1626561 TI - Angiotensin-converting enzyme inhibitors and lithium toxicity. PMID- 1626562 TI - Direct fine needle aspiration cytology. PMID- 1626563 TI - Clinical characteristics and pathophysiology of erythromelalgia and erythermalgia. PMID- 1626564 TI - Autoimmune diseases, IgA deficiency, and intravenous immunoglobulin treatment. PMID- 1626565 TI - Interferon for mixed cryoglobulinemia associated with hepatitis C. PMID- 1626566 TI - Use of ice-water bag to obtain dive reflex. PMID- 1626567 TI - Parity and incidence of non-insulin-dependent diabetes mellitus. AB - PURPOSE: To examine prospectively the association between parity and subsequent incidence of non-insulin-dependent diabetes mellitus (NIDDM). Most previous studies have not controlled for potential confounding by age and obesity. PATIENTS AND METHODS: In a prospective cohort study, 113,606 United States registered nurses aged 30 to 55 years and free of diagnosed diabetes, coronary heart disease, stroke, and cancer at baseline were followed for 12 years. Endpoint was incidence of confirmed NIDDM. RESULTS: During 1,278,188 person-years of follow-up, we confirmed 2,310 incident cases of NIDDM. An apparent association between parity and diabetes was observed in unadjusted analyses (relative risk = 1.56 [95% confidence interval (CI), 1.27 to 1.91] among women with six or more births compared with that in nulliparous women) (p, trend less than 0.00001). This association was attenuated after adjustment for age (relative risk = 1.19 [CI 0.97 to 1.48], p, trend = 0.06) and was completely abolished after adjustment for both age and body mass index (relative risk = 0.95 [CI 0.75 to 1.19], p, trend = 0.19). Multivariate adjustment for family history of diabetes, age at first birth, hormone use, and other variables did not materially alter these findings. There was no important modifying effect of family history of diabetes on these associations. CONCLUSIONS: Despite a temporary diabetogenic effect of pregnancy, parity is not associated with an increased risk of subsequent clinical NIDDM. These data underscore the importance of control for confounding by age and obesity in evaluating these associations. PMID- 1626568 TI - Preoperative evaluation for diabetic renal transplantation: impact of clinical, laboratory, and echocardiographic parameters on patient and allograft survival. AB - OBJECTIVE: To assess the impact on renal transplant patients and graft survival of clinical, laboratory, and echocardiographic parameters commonly measured prior to surgery. PATIENTS: Forty-seven consecutive diabetics with preoperative echocardiograms at the time of transplantation. METHODS: Clinical history, standard chest roentgenogram, electrocardiogram, blood tests, echocardiograms, and HLA testing at baseline; follow-up from 2 to 7 years with periodic reassessment of graft function. RESULTS: Patient survival did not appear to be influenced by age, sex, or type of allograft. A history of either myocardial infarction, congestive heart failure, or angina was present in 15 patients with 3 year survival of 50% (72% if not present, p less than 0.05). Histocompatibility testing did not impact on survival. Serum sodium, potassium, calcium, phosphate, and calcium-phosphate product did not discern different survival groups. A hematocrit greater than 30% was present in 15 patients with 3-year survival of 43% (73% if not present, p less than 0.05). Greater than 10% antibody sensitization of the recipient resulted in a 3-year survival of 38% in eight patients (68% if not present, p less than 0.05). Radiologic evidence of cardiomegaly or congestive heart failure and standard electrocardiographic evidence for left ventricular hypertrophy or strain did not impact on survival. Echocardiographic measurements of left ventricular end-diastolic diameter, posterior wall thickness, or ejection fraction were also not predictive. Increased end-systolic diameter (10 patients, 30% 3-year survival versus 69%, p less than 0.05) and decreased velocity of circumferential fiber shortening (11 patients, 45% 3-year survival versus 71%, p less than 0.05) both appeared to be related to survival. Increased accuracy of prediction could be obtained by adding risk factors so that a history of coronary artery disease and increased end systolic diameter predicted 3-year survival of 42% versus 82% if neither was present. In terms of graft survival, no clinical, radiographic, or electrocardiographic result yielded predictive information. Among the laboratory tests, only highly antibody-sensitized patients (eight patients, 0% 3-year survival versus 66% 3-year survival, p less than 0.001) showed different survival patterns. Echocardiographic elevated end-systolic diameter predicted a significantly (p less than 0.001) decreased graft survival (3-year survival 33% versus 63%). CONCLUSION: Preoperative prediction of patient and graft survival in diabetic renal transplantation may be enhanced by echocardiographic assessment of systolic load and function. For patients with normal systolic function, whose hematocrit is below 30%, with preformed antibodies less than 10%, renal transplantation has an excellent prognosis; invasive cardiac procedures are not likely required. Since these risk factors are likely additive, a high-risk group may be identified. These latter patients should undergo coronary angiography. PMID- 1626569 TI - Nonresolving pneumonia in steroid-treated patients with obstructive lung disease. AB - PURPOSE: To review autopsy-proven cases of opportunistic pneumonia and determine how many of these patients had received corticosteroid therapy for obstructive lung disease in order to define whether this therapy was the major risk factor predisposing to infection. PATIENTS AND METHODS: All autopsies performed at Winthrop-University Hospital over a 5-year period were reviewed, and 30 cases of opportunistic pneumonia were identified. In eight of 30 cases, corticosteroid therapy for chronic obstructive pulmonary disease (COPD) was the only identifiable risk factor for opportunistic infection. The other 22 patients had other well-defined risk factors for infection. Chart review of the eight patients with COPD was undertaken to define the clinical features of their infections. RESULTS: All eight patients had a progressive multilobar pneumonia that failed to resolve, either clinically or radiographically, despite the use of multiple broad spectrum antibiotics. In four cases, the infection was community-acquired, while in the other four cases, it was nosocomial in origin. Despite the presence of a nonresolving pneumonia, opportunistic infection was generally not considered as a diagnostic possibility, with only one case being correctly diagnosed antemortem. Autopsy examination documented Aspergillus species as being responsible for six episodes of pneumonia, Candida albicans accounting for one episode, and cytomegalovirus accounting for one episode. CONCLUSION: Based on this experience, it is clear that corticosteroid therapy of COPD can lead to opportunistic pulmonary infection, in or out of the hospital. This diagnosis should be considered when patients receiving this therapy develop a pneumonia that fails to respond to broad-spectrum antibiotics. PMID- 1626571 TI - Peritoneal dialysis in end-stage renal disease patients with preexisting chronic liver disease and ascites. AB - PURPOSE: Hemodialysis in patients with chronic liver disease and ascites may be complicated by intradialytic hypotension, limiting the amount of ultrafiltration and resulting in massive ascites. Successful maintenance peritoneal dialysis (PD) has not been previously reported as an alternative to hemodialysis in this population. PATIENTS AND METHODS: Nine patients with chronic renal failure, chronic liver disease, and tense ascites prior to beginning PD are described. All chronic PD catheters were placed percutaneously by the nephrology staff. Seven patients were maintained primarily on continuous ambulatory peritoneal dialysis, whereas two were on intermittent peritoneal dialysis. RESULTS: PD catheters were placed without serious hemorrhage or bowel injury. PD provided adequate clearance and volume maintenance for each patient. Fifteen episodes of peritonitis occurred in 18 patient-years of PD. All episodes of peritonitis were successfully treated with intraperitoneal antibiotics without catheter removal. Only one patient had a decline in the serum albumin level of 0.5 g/dL or more during the course of chronic PD. Three of the nine patients are still alive and on PD for durations of 18 to 24 months. One patient insidiously developed sclerosing peritonitis after 8 years on PD and is now on hemodialysis, and another patient switched to hemodialysis because she was no longer able to care for herself or to manage her PD. Four patients died while maintained on PD; three deaths were due to complications of liver failure within the first 4 months of PD and the fourth was due to empyema after 4 years of PD. CONCLUSION: PD can be used successfully to treat chronic renal failure in patients with chronic liver disease and ascites when the liver disease itself is not rapidly fatal. PD may be better tolerated than hemodialysis and perhaps should be the renal replacement treatment of choice in these patients. PMID- 1626570 TI - A Danish kindred with familial amyloid cardiomyopathy revisited: identification of a mutant transthyretin-methionine111 variant in serum from patients and carriers. AB - PURPOSE: In familial amyloid cardiomyopathy of Danish origin, the amyloid microfibrils contain a mutant transthyretin (TTR) with a methionine-for-leucine substitution at the molecular position 111. We studied the possible occurrence of this variant TTR-Met111 in serum from afflicted as well as nonafflicted family members and their offspring, in order to define its possible role as predictor of the disease and to describe its mode of inheritance. PATIENTS AND METHODS: Stored, frozen serum samples obtained from 1959 through 1960 from 36 of 40 living members of the kindred were analyzed. The method employed to detect the abnormal TTR was based on the electrophoretic separation of fragments produced by cyanogen bromide cleavage at the two methionine sites. RESULTS: All sera from family members with amyloid cardiomyopathy contained the variant transthyretin TTR Met111 as did sera from half of their offspring. In contrast, nonafflicted family members and their offspring were seronegative for TTR-Met111. Three cousins from the second generation died between 1980 and 1986 of amyloid cardiomyopathy. The presence of variant TTR-Met111 preceded their deaths by 20 to 26 years. CONCLUSIONS: The occurrence in serum of the mutant transthyretin TTR-Met111 is linked to the occurrence of amyloid cardiomyopathy in patients and their offspring, while unafflicted branches of the family are negative for the variant protein. That the occurrence in serum of TTR-Met111 precedes the onset of clinical amyloid cardiomyopathy by several decades makes the variant TTR a marker for the disease. The distribution of afflicted family members and seropositivity for the variant TTR shows an autosomal dominant mode of inheritance. CLINICAL SIGNIFICANCE: The results make possible early detection of potential patients and provide tools for genetic counseling. Cardiac transplantation may provide a new therapeutic option. PMID- 1626572 TI - Very low doses of GM-CSF administered alone or with erythropoietin in aplastic anemia. AB - PURPOSE AND RATIONALE: There has been no previously published experience with granulocyte-macrophage colony-stimulating factor (GM-CSF) at doses less than 15 micrograms/m2/d in patients with aplastic anemia, and most observations have been made at doses of 100 to 500 micrograms/m2/d (2.5 to 12.5 micrograms/kg/d). The benefits of using considerably lower doses, if effective, should include a decrease in cost and in side effects. We have therefore used very low doses of GM CSF to treat a group of patients with aplastic anemia. Additionally, since severe anemia is often a problem in these patients, we recently started administering erythropoietin along with the GM-CSF. Herein we report the results of very-low dose GM-CSF therapy in patients with aplastic anemia and our preliminary findings in those individuals who received combination therapy. PATIENTS AND METHODS: We administered recombinant human GM-CSF subcutaneously at doses of 5 to 20 micrograms/m2/d ("very-low-dose GM-CSF") to 12 patients with aplastic anemia. In addition, a 13th patient received erythropoietin together with the GM-CSF regimen, and three of the 12 individuals who initially received 1 or more months of GM-CSF alone were later also given erythropoietin (4,000 U/d subcutaneously). RESULTS: In five of 12 patients (42%) treated with very-low-dose GM-CSF, an increase in neutrophil counts (2.0- to 6.7-fold) was noted, and one of these subjects attained a bilineage response (neutrophil counts, 0.3 to 1.75 x 10(9)/L; platelet counts, 8 to 169 x 10(9)/L). Moreover, a sixth patient showed a rise in platelet counts (19 to 80 x 10(9)/L) without a concomitant increase in neutrophils. Constitutional side effects were minimal. Combining erythropoietin and very-low-dose GM-CSF produced a bilineage response (neutrophils, 1.0 to 3.0 x 10(9)/L; hemoglobin, 7.4 to 9.4 g/dL) in the one patient who received erythropoietin together with the GM-CSF from the time that GM-CSF was initiated. In one of the other patients who were given combination therapy, the addition of erythropoietin appeared to enhance the response; this patient demonstrated a neutrophil response to GM-CSF alone and a trilineage response (neutrophils, 0.8 to 3.75 x 10(9)/L; hemoglobin, 7.0 to 13.1 g/dL; and platelets, 10 to 34 x 10(9)/L) to the combination. No toxicity was associated with the addition of erythropoietin. CONCLUSIONS: Our observations suggest that (1) very low doses of GM-CSF (5 to 20 micrograms/m2/d subcutaneously) may be used initially in neutropenic patients with aplastic anemia, and the dose subsequently increased only in patients who do not respond; and (2) the administration of erythropoietin together with GM-CSF is well tolerated, can augment responsiveness in some patients, and deserves further study. PMID- 1626573 TI - Diagnosis and treatment of outpatient insomnia by psychiatric and nonpsychiatric physicians. AB - Insomnia is commonly encountered in general medical practice, but little is known about how primary care physicians manage this problem. We reviewed medical records describing 536 patient encounters in which either triazolam (Halcion) or flurazepam (Dalmane) was prescribed for outpatient use. Only 12% of the progress notes written by internists or surgeons contained even a remote reference to sleep, whereas 74% of psychiatrist's notes contained at least some sleep symptom documentation. In a multivariate analysis including the number of medical and psychiatric diagnoses, patient age, and physician gender, only the prescriber department was independently associated with the presence of symptom documentation. We also found that 30% of the prescriptions written by internists or surgeons were for inappropriately large quantities of these drugs (180 or more doses) compared with 6% of the prescriptions written by psychiatrists. We conclude that the evaluation of insomnia by nonpsychiatrists is often incomplete and that hypnotic drugs may be inappropriately prescribed by these physicians. Further efforts are needed to improve the management of insomnia by primary care physicians in the outpatient setting. PMID- 1626574 TI - Tapping the child's perspective. PMID- 1626575 TI - Cirrhosis in a 66-year-old woman. PMID- 1626576 TI - Prevalence of neurosyphilis in human immunodeficiency virus-infected patients with latent syphilis. AB - PURPOSE: A prospective study was done to determine the prevalence of confirmed neurosyphilis (cerebrospinal fluid [CSF] Venereal Disease Research Laboratory [VDRL]-reactive) in human immunodeficiency virus (HIV)-infected patients with latent syphilis (reactive serum rapid plasma reagin [RPR] and microhemagglutination-Treponema pallidum [MHA-TP]). PATIENTS AND METHODS: All HIV infected patients seen for their first visit at the Los Angeles County/University of Southern California Medical Center AIDS Clinic from June through December 1990 were screened for latent syphilis. Those with reactive serum RPRs and MHA-TPs who had not received recent (within 6 months) therapy for syphilis were offered diagnostic CSF sampling. RESULTS: A total of 312 patients were screened, of whom 71 (22.8%) had reactive serum RPRs and MHA-TPs. Thirty-three of these patients (47%) had diagnostic CSF sampling (26 refused lumbar puncture or were lost to follow-up; 12 had had recent therapy for syphilis and thus did not have CSF sampling). Among the 33 patients who had CSF sampling, 20 (60.6%) had normal CSF profiles (white blood cell count less than 8/mm3; protein less than 0.60 g/L; glucose greater than 2.8 mmol/L) and nonreactive CSF VDRLs. Ten of the 33 patients (30.3%) had abnormal CSF profiles and nonreactive CSF VDRLs, and three of 33 (9.1%) had reactive CSF VDRLs. CONCLUSIONS: Asymptomatic neurosyphilis was found in 9.1% of our patient population undergoing CSF sampling, giving a 1.0% prevalence of CSF VDRL-reactive neurosyphilis in the population we screened. The abnormal CSF findings may have been due to either nonreactive CSF VDRL neurosyphilis, central nervous system infection with HIV, or infection with some unrecognized agent. PMID- 1626577 TI - Subacute bacterial endocarditis secondary to Streptococcus pneumoniae. AB - Pneumococcal endocarditis characteristically presents as an acute illness, often accompanied by purulent meningitis, rapid destruction of the heart valves, congestive heart failure, and high mortality. We describe two patients with subacute pneumococcal endocarditis without a known primary source of pneumococcal bacteremia, fever, meningitis, or congestive heart failure. Both patients were cured with medical therapy. Pneumococcal endocarditis can present as an indolent illness resembling viridans streptococcal endocarditis. PMID- 1626578 TI - Severe hepatotoxicity in a patient receiving both acetaminophen and zidovudine. AB - We report the development of severe hepatotoxicity in a patient on zidovudine therapy who received 3.3 g of acetaminophen in less than 36 hours. Three days later, the patient's serum aspartate aminotransferase level was 5,724 U/L, alanine aminotransferase was 3,124 U/L, lactate dehydrogenase was 12,675 U/L, alkaline phosphatase was 84 U/L, and total bilirubin was 20 mumol/L. These values substantially improved over the ensuing 4 days. Serologic results for hepatitis B, hepatitis A, and cytomegalovirus were all negative. The pattern and time sequence of transaminase elevation in this patient are consistent with acute acetaminophen hepatotoxicity, especially since zidovudine-induced hepatotoxicity is described as producing cholestasis rather than acute hepatitis. We hypothesize that our patient's susceptibility to acetaminophen-dependent hepatotoxicity may have been augmented by competitive utilization of glucuronidation by other drugs such as zidovudine and/or trimethoprim-sulfamethoxazole with subsequent increased cytochrome P450-dependent metabolism of acetaminophen. Additionally, due to malnutrition and/or to human immunodeficiency virus infection per se, our patient may have had decreased hepatic reserves of glutathione with which to conjugate the toxic acetaminophen product of the P450 system. Although severe acetaminophen associated hepatotoxicity has not previously been reported in patients receiving zidovudine, we suggest that clinicians be aware of this potential interaction and counsel malnourished patients, especially those with concomitant hepatic disease, to exercise caution when taking both these medications. PMID- 1626579 TI - Diagnosis and treatment of granulomatous mastitis. AB - Granulomatous mastitis is a benign inflammatory breast disease of unknown etiology. Although it is rare, it frequently presents in a manner similar to that of breast carcinoma. Surgical resection of the affected tissue has often been the method of treatment, but many patients have experienced recurrences. Corticosteroids have also been used, but the initiation of this therapy is often limited by concerns related to the presence of an infectious etiology. Presented here are two cases that demonstrate the efficacy of corticosteroids in this condition after appropriate evaluation is performed. PMID- 1626580 TI - Summer frustrations. PMID- 1626581 TI - One bias at a time. PMID- 1626582 TI - Do they really understand us? PMID- 1626583 TI - The muddy waters of clinical teaching. PMID- 1626584 TI - Rescue operations for snakebite. PMID- 1626586 TI - Slimefighters! PMID- 1626585 TI - Corralling atrial fibrillation with 'maze' surgery. PMID- 1626587 TI - What do you say when you delegate work to others? PMID- 1626588 TI - How to predict and prevent pressure ulcers. PMID- 1626589 TI - Making a critical difference. PMID- 1626590 TI - Backlash signs and symptoms. PMID- 1626591 TI - The fifth sound. PMID- 1626592 TI - An HIV-infected pharmacist. PMID- 1626593 TI - The psychoanalysis of an adult survivor of incest: a case study. PMID- 1626594 TI - A case report: Part II. PMID- 1626595 TI - Updike: fiction and the writer's access to contradictory ego states. PMID- 1626596 TI - Don Pasquale, Fidelio, and psychiatry. AB - Donizetti's Don Pasquale and Beethoven's Fidelio are discussed in order to illustrate how two very different operas can illustrate the human quest for authenticity. Through their music and dramatic presentation they are able to convey experiential insights into profound philosophic and psychologic truths. Along with other experiential communications, such as myths, folklore, poetry, humor, and art, they can be especially helpful--not only but also--in psychotherapy, in providing access to potentials that ordinarily are sealed off, in enhancing the awareness of inauthentic attitudes, in facilitating the acceptance of seemingly paradoxical aspects of human existence, and in providing a deeper sense for life's meaningfulness. Music is invaluable in opening our soul to the story's thoughts, feelings, and commitments. PMID- 1626597 TI - On Freud's admiration for Beethoven and his "splendid creations". PMID- 1626598 TI - Direct interpretation of dreams: some basic principles and technical rules. PMID- 1626599 TI - Different perspectives of inventory management among physicians and hospital administrators. PMID- 1626600 TI - Colorectal carcinoma associated with ulcerative colitis: a study of prognostic indicators. AB - Fifty-two patients with ulcerative colitis and colorectal cancer undergoing colectomy at the Mount Sinai Hospital between 1973 and 1988 were studied retrospectively to determine the correlation of age, sex, duration of colitis, tumor location, number of cancers, tumor differentiation, colloid content, presence of signet ring cells, Dukes' classification, and DNA ploidy with survival. The mean age was 45 years, with a mean duration of colitis of 21 years. Five patients (10%) had Dukes' A lesions, 17 (33%) had Dukes' B lesions, 17 (33%) had Dukes' C lesions, and 13 (25%) had distant metastases. Thirty patients (58%) had well- or moderately differentiated tumors, whereas tumors were poorly differentiated in 22 (42%). Twenty-eight patients (54%) had colloid tumors, and, in 14 (27%), signet ring cells were present. Thirty-one patients (60%) had nondiploid tumors. Actuarial analysis revealed that the 5-year survival rate was significantly worse for patients with nondiploid tumors (76% versus 32%). When stratified by stage, only patients with Dukes' C lesions showed a significant difference in survival for diploid versus nondiploid tumors. Multivariate analysis showed that the Dukes' classification was the best prognostic indicator, followed by tumor differentiation and DNA ploidy. Tumor location, colloid content, number of cancers, duration of disease, age, and sex did not correlate with the prognosis. PMID- 1626601 TI - Surgery for recurrent rectal adenocarcinoma in the presence of hydronephrosis. AB - From January 1974 to December 1989, 16 patients with locally recurrent rectal adenocarcinoma and hydronephrosis underwent exploratory celiotomy with curative intent. There were eight males and eight females. The median age was 61 years. Primary rectal adenocarcinomas were treated with abdominoperineal resection in 12 patients and low anterior resection in 4 patients. Four patients underwent adjuvant radiotherapy, one patient adjuvant chemotherapy, and one patient combination therapy. The median disease-free interval between resection of the primary tumor and recurrence was 18 months. Hydronephrosis was unilateral in seven patients (44%), and bilateral in nine patients (56%). Preoperative evaluation indicated that all 16 patients had local pelvic-perineal recurrence or pelvic recurrence alone. Resection was not possible in any of these 16 patients for the following reasons: 5 patients (31%) had pelvic sidewall involvement and carcinomatosis; 3 patients (19%) pelvic sidewall involvement alone; 2 patients (13%) pelvic sidewall involvement and sacral fixation; and 2 patients (13%) had sacral fixation alone. In the remaining four patients, there was pelvic sidewall involvement by tumor and/or synchronous hepatic metastases, carcinomatosis, or sacral fixation. The median survival after exploratory celiotomy was 8 months in the 16 patients who died of their disease. Unilateral and bilateral hydronephrosis appears to be a contraindication for potentially curative surgical resection in recurrent rectal adenocarcinoma. PMID- 1626602 TI - Reevaluation of current transfusion practices in patients in surgical intensive care units. AB - Widespread interest in the complications associated with packed red blood cell (PRBC) transfusions has led to the scrutiny of traditional transfusion practices. Recently, attempts have been made to define more clearly the indications for PRBC transfusions in patients, particularly those who are critically ill. At present, however, transfusions continue to be ordered based on a hemoglobin level less than 10 g/dL. We report herein the impact on oxygen consumption of PRBC transfusions administered for a hemoglobin concentration less than 10 g/dL in 30 surgical intensive care unit patients who were euvolemic and hemodynamically stable. For the group as a whole, transfusion had a negligible effect on oxygen consumption. Fifty-eight percent of all such transfusions failed to change oxygen consumption by greater than 10% and could therefore be considered of questionable benefit. PMID- 1626603 TI - Predictability of clinicobiochemical scoring systems for early identification of severe gallstone-associated pancreatitis. AB - Early identification of severe gallstone-associated acute pancreatitis (GAAP) is a prerequisite for treatment with urgent endoscopic sphincterotomy. This study assesses the value of two clinicobiochemical scoring systems to this end. Over the 7-year period from 1983 to 1989, 100 consecutive patients with acute pancreatitis (45 related to gallstones, 36 to alcohol, and 19 of undetermined etiologies) had clinicobiochemical analysis within 48 hours of admission. The final diagnosis and outcome were retrospectively compared with the prediction achieved by the scoring systems. With regard to Blamey's criteria for early identification of gallstones, significant differences were found between the biliary and nonbiliary groups with respect to female sex, serum amylase concentration greater than or equal to 4,000 IU/L, alkaline phosphatase level greater than or equal to 300 IU/L, and alanine aminotransferase level greater than or equal to 100 IU/L (all p values less than 0.001). Age greater than or equal to 50 years was found to be significant (p less than 0.02) only in differentiating gallstone- versus alcohol-associated acute pancreatitis. When three or more positive factors were present, the sensitivity and specificity for predicting gallstones were 60% and 87%, respectively; the predictive value of a positive result was 79%, of a negative result 74%, and the overall accuracy was 75%. At a cutoff level of five, rather than three or more prognostic factors, the modified Ranson's criteria for patients known as having GAAP allowed a suitable discrimination of patients with an expected high risk of complications and mortality. When the two scoring systems (Blamey greater than or equal to 3 and Ranson greater than or equal to 3) were combined, 17 patients were predicted as having severe GAAP: 6 of these 17 patients were misdiagnosed as having biliary pancreatitis, whereas 9 patients with definite severe GAAP were not selected because of a Blamey score less than 3. More specific diagnostic tools are needed, and higher cutoff levels for prognostic scores are required for the prediction of severe GAAP, particularly in view of selecting patients for potentially dangerous approaches such as urgent endoscopic sphincterotomy. PMID- 1626604 TI - Diagnosis and management of 17 consecutive patients with inflammatory abdominal aortic aneurysm. AB - This report reviews the authors' experience in diagnosing and managing 17 consecutive patients with inflammatory abdominal aortic aneurysm (AAA). Among 491 patients undergoing repair for AAA during a 10-year period, 17 (3%) had evidence of associated periaortic fibrosis, which was confirmed histologically. No patient had acute rupture, and two patients (12%) had chronic contained rupture. Ureteral obstruction was evident in seven patients. In 41% of the patients, available surgical correlation demonstrated that computed tomographic (CT) scan accurately delineated the extent of the disease. Sixteen patients underwent aneurysm resection. Ureteral obstruction was relieved by ureterolysis in three patients treated early in this series. In the last period of the study, well-documented hydronephrosis spontaneously subsided in two patients without special treatment. Of these 17 patients, 15 (88%) were early (30-day) survivors. There were two late deaths at 2 months and 5 years; 12 (71%) patients are still alive and free of symptoms up to 10 years after operation. On the basis of our study, we conclude the following: (1) precise preoperative diagnosis and detailed anatomic information are widely available with CT; (2) aneurysm resection is the treatment of choice because the risk of rupture still exists, and this procedure seems to reverse the inflammatory process; (3) good early and late results can be expected with proper surgical technique; and (4) routine follow-up with CT is recommended to document resolution or progression of the fibrotic process after aneurysm resection. PMID- 1626605 TI - Twelve-year follow-up of a prospective, randomized trial of selective vagotomy with pyloroplasty and selective proximal vagotomy with and without pyloroplasty for the treatment of duodenal, pyloric, and prepyloric ulcers. AB - Between 1973 and 1981, 161 patients with prepyloric, pyloric, or duodenal ulcers were randomly allocated to selective vagotomy with pyloroplasty, selective proximal vagotomy with pyloroplasty, or selective proximal vagotomy alone. No significant differences in clinical results were found 3 years after surgery by Emas and Fernstrom (Am J Surg 1985; 149: 236-42). There was one postoperative death, and one patient lost to follow-up. Of 159 patients, 52 underwent selective vagotomy with pyloroplasty, 55 selective proximal vagotomy with pyloroplasty, and 52 selective proximal vagotomy alone. Fifteen patients did not undergo endoscopy, but they had no epigastric complaints. From 1 to 16 years after surgery, recurrent ulcer was detected in 13%, 18%, and 23%, respectively, after selective vagotomy with pyloroplasty, selective proximal vagotomy with pyloroplasty, or selective proximal vagotomy without pyloroplasty. Twenty-eight percent of the patients with recurrent ulcer had no symptoms and received no treatment. Sixteen patients died within 8 years after surgery of causes unrelated to the ulcer disease. At their final examination, 14 of the 16 patients had Visick I or II (modified Visick scale) results, and the disease that caused their deaths obscured evaluation in 2 patients. The remaining 143 patients were followed up for 8 to 16 years (average: 12 years). Epigastric pain with or without ulcer was recorded more often (significant) after selective proximal vagotomy alone (40%) than after selective vagotomy with pyloroplasty (17%) or selective proximal vagotomy with pyloroplasty (14%). Bowel habits were unchanged in 96% of patients who underwent selective vagotomy with pyloroplasty or selective proximal vagotomy with pyloroplasty and 100% of patients who had selective proximal vagotomy alone. Mild dumping tended to be more common after vagotomy with pyloroplasty but was a minor nuisance in only a few patients. Very good or good results (Visick I or II) were recorded in 75% of the patients after selective vagotomy with pyloroplasty or selective proximal vagotomy with pyloroplasty or selective proximal vagotomy with pyloroplasty and in 54% after selective proximal vagotomy alone (significant difference). Seventeen patients underwent reoperation with antrectomy and gastrojejunostomy Roux-en-Y (13 patients) or gastroduodenostomy (4 patients) with no mortality. The results of the reoperations were graded as Visick I or II results in all but one patient. The final grading, including the reoperations, were Visick I or II in 85% of patients after selective vagotomy with pyloroplasty and selective proximal vagotomy with pyloroplasty and in 55% after selective proximal vagotomy alone (significant difference).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1626606 TI - Absorption of Intralipid and interferences from nutrients infused into the peritoneal cavity of the rat. AB - We studied the peritoneal absorption and elimination of Intralipid after its intraperitoneal and intravenous infusion into rats, by means of a two-compartment model. Follow-up measurements of the plasma triglyceride rate were made. The peritoneal absorption of Intralipid gives the following absorption and elimination constants: Ka (absorption constant from the peritoneal cavity) is 0.106 +/- 0.08 h-1; Ke (elimination constant from the blood stream) is 0.0440 +/- 08 h-1; and BAa (absolute bioavailability) is 84.5 +/- 0.08% 8 hours after infusion. These results show that the intraperitoneal absorption of Intralipid is high and progressive during the first 8 hours, thus supplying the daily caloric needs of the animal through the administration of a single bolus administration, and the plasma triglyceride clearance is faster than the intraperitoneal absorption after the first 6 hours, thus avoiding dangerous overloads. We also studied the behavior of different combinations of glucose, amino acids, and fats infused into the peritoneal cavity of rats in order to observe possible interferences with the absorption of these nutrients. Two microcuries of radioactive L-glucose-1-C14 with 5 mL of 5% D-glucose, with 5 mL of 3.5% amino acid solution, or with 5 mL of 20% fat emulsion were infused intraperitoneally into three different groups of animals. Slight differences of plasma radioactivity were registered among these three groups 1 hour after infusion. Likewise, small differences of plasma radioactivity were observed between the animals receiving an infusion of 1 microCi of five L-amino-acids-U-C14 diluted with 5 mL of 3.5% amino-acid solution, with 5 mL of 5% glucose solution, or with 5 mL of 20% fat emulsion 4 and 6 hours after infusion. No differences in the plasma triglyceride rates were observed between those groups of animals infused with 5 mL of 20% Intralipid plus 5 mL of glucose solution or with 20% Intralipid plus 3.5% amino-acid solution compared with the group receiving only 5 mL of 20% Intralipid. The infusion of fats does not seem to interfere with that of other substrates, possibly because of the different absorption route (lymphatic for fats and capillary vessels for amino acids and glucose solutions), but further research is needed to reach conclusive results. Perhaps the prolonged administration of fat, together with other substrates, produces precipitates and other galenic problems that hinder absorptive mechanisms of the preparations. PMID- 1626607 TI - Use of color Doppler imaging in the distinction between thyroid and parathyroid lesions. AB - To determine whether the use of color Doppler imaging in conjunction with standard high-resolution 10-MHz ultrasound could increase the screening sensitivity in distinguishing between thyroid and parathyroid lesions in the detection of parathyroid disease, we studied 32 patients with hyperparathyroidism with both modalities who were subsequently treated surgically. Among these 32 patients, parathyroid lesions were predominantly avascular (n = 21, average size 0.9 x 0.6 cm) but with increased size demonstrated some vascularity (n = 9, average size 2.1 x 1 cm, 32%). Of these 32 patients, 46.6% had thyroid lesions as well. Thyroid lesions were avascular when small (n = 26 lesions, average size 0.5 x 0.5 cm) but tended to demonstrate vascularity (n = 14, 35%) at about 1 cm in size or greater. Although the addition of color Doppler imaging enabled the differentiation of vessel from soft-tissue abnormalities and some distinction between parathyroid and thyroid lesions, it had no effect on overall sensitivity (65%) in the detection of parathyroid disease. PMID- 1626608 TI - Claviculectomy for the exposure and en bloc resection of adjacent tumors. AB - Claviculectomy has been described for primary or metastatic tumors of the clavicle. In 11 patients, claviculectomy was used as a technical expedient for the exposure and en bloc resection of large, underlying nodal metastases from melanoma (7 patients) and soft tissue tumors (4 patients). There were no wound complications. Three patients developed moderate edema of the arm. There was little limitation at the shoulder, and the use of the upper extremity has been essentially normal. Claviculectomy is well tolerated, provides good exposure of the underlying neurovascular structures, and, in some patients, provides a method of limb salvage for underlying tumors in preference to forequarter amputation. PMID- 1626609 TI - A technique for converting a needle-catheter jejunostomy into a standard jejunostomy. AB - The benefits of enteral nutrition for surgical patients have been well documented in the literature, and needle catheter jejunostomy is frequently used at initial surgical exploration. Occasionally, the need arises for prolonged use of the catheter, and problems occur with occlusion of the catheter. A simple technique is described for converting the needle-catheter jejunostomy into a standard feeding jejunostomy. PMID- 1626610 TI - Novel antibody drug products. AB - Recent developments in protein and genetic engineering methods have allowed the production of antibody-derived molecules that have important potential as therapeutic agents. Although monoclonal antibodies of murine origin have been used for therapeutic purposes, limitations due to anti-antibody responses and suboptimal effectiveness for some indications, such as tumor cell killing, have led to the development of human monoclonal antibodies, chimeric and complementarity determining-region grafted antibodies, immunotoxins, and other engineered products. These novel antibodies are being tested for the treatment and prevention of infectious diseases and for the diagnosis and treatment of cancers, as well as for indications considered nontraditional for antibodies (e.g., as antithrombotics or inhibitors of neutrophil adherence). The availability of antibody drug products raises a number of issues for clinicians. Among these are new patterns of adverse effects, immunogenicity (development of anti-antibody response), important questions regarding administration and dosage, and substantial cost implications. PMID- 1626611 TI - Drug therapy for inflammatory bowel disease: Part I. AB - In a two-part series, recent improvements in drug therapy for inflammatory bowel disease are reviewed. Part I summarizes aminosalicylates and corticosteroids. The active moiety of sulfasalazine, which is 5-aminosalicylic acid (mesalamine), in topical or oral form is as effective as sulfasalazine for treatment and prophylaxis of ulcerative colitis and is tolerated by 80% of sulfasalazine intolerant patients. Coated forms of mesalamine have a potential advantage in the treatment of Crohn's ileitis in that these forms do not require bacterial cleavage for activity. New rapidly metabolized corticosteroids (budesonide, tixocortol pivalate, beclomethasone dipropionate) in topical and oral forms are emerging as equivalent therapy to standard corticosteroids but are associated with less adrenal suppression. PMID- 1626612 TI - Management of mandibular fractures. PMID- 1626613 TI - A clinical approach to dysphagia. PMID- 1626614 TI - Prevention and management of intubation injury of the larynx and trachea. PMID- 1626615 TI - Infections of the external ear. PMID- 1626616 TI - Reconstructive alternatives following segmental mandibulectomy. PMID- 1626617 TI - c-myc oncogene copy number in squamous carcinoma of the head and neck. AB - PURPOSE: Altered resident cellular genetic sequences (oncogenes) may result in malignant transformation, maintenance of tumor growth, and metastatic propensity. In this pilot study, we have elected to probe c-myc oncogene in evaluating specimens from human squamous cell carcinoma. MATERIALS AND METHODS: Samples were obtained from 24 patients with squamous cell carcinoma of the head and neck. The ratio of tumor DNA values to that of control DNA was used to estimate the c-myc copy number. RESULTS: Data from material obtained from eight patients was analyzed to the point of c-myc copy number. Tumors varied from stage II through IV. Five originated in the oral cavity and three in the larynx. Analysis of primary tumors demonstrated that two of eight had increased c-myc copy numbers. Histologically positive neck specimens were encountered in five of the study patients. Three demonstrated elevated c-myc copy numbers, two of which had had increased copy number at the primary site. CONCLUSION: This study confirms that c myc amplification can be present in squamous cell carcinoma of the head and neck. c-myc Amplification may also be present in neck metastasis. Oncogene amplification in neck metastasis may indicate an increased metastatic propensity for individual tumor cells demonstrating c-myc amplification. PMID- 1626618 TI - The total reconstruction of the tympanic membrane by the "crowncork" technique. AB - PURPOSE: The "crowncork tympanoplasty" is a technique for the total reconstruction of the tympanic membrane. It is recommended in cases of ear malformation, blunting phenomena, and total deficiency of the membrane caused by chronic otitis media. PATIENTS AND METHODS: The records of 12 patients undergoing "crowncork tympanoplasty" were reviewed. This includes 5 patients who were operated on because of middle ear malformation, 6 cases with a blunting phenomena following prior tympanoplasty, and 1 patient with chronic otitis media. RESULTS: In each case an intact tympanic membrane was achieved. The air bone was reduced to 17, 19, 16, and 11 dB in the frequency 500, 1,000, 2,000, and 4,000 Hz. CONCLUSION: The use of cartilage for tympanoplasty has been useful despite the comparatively worse vibration characteristics of the rigid material. Total reconstruction of selected problem cases using this "crowncork technique" has resulted in good healing with favorable hearing results and should be incorporated into the routine of the skilled otosurgeon. PMID- 1626619 TI - alpha-Fluoromethylhistidine but not diphenhydramine prevents motion-induced emesis in the cat. AB - PURPOSE: This study seeks to evaluate the comparative role of alpha fluoromethylhistidine and diphenhydramine in the prevention of motion sickness. METHOD: The role of histaminergic mechanisms in motion sickness were evaluated in a feline model. Twenty-six female cats were studied. A variety of doses of fluoromethylhistidine and diphenhydramine were administered before motion testing. RESULTS: Fluoromethylhistidine was effective in preventing motion sickness. The efficacy was dose dependent. In contrast, diphenhydramine failed to prevent motion sickness in any of the tested doses. CONCLUSIONS: The failure of diphenhydramine to prevent motion sickness was unexpected. This may reflect the route of administration or the animal model studied. Depletion of histamine with fluoromethylhistidine prevented motion sickness in cats. Our results suggest that this drug may provide a very long duration of protection in cats. PMID- 1626621 TI - Genetics of the Rett syndrome. AB - The current knowledge concerning the inheritance of the Rett syndrome is reviewed. So far the main interest has been focused on the short arm of the X chromosome as the possible location for the gene for the Rett syndrome. There is, however, no conclusive evidence for such a location. The authors suggests that other possible gene locations also should be investigated. PMID- 1626620 TI - Chronic respiratory distress caused by radiolucent esophageal foreign body. PMID- 1626622 TI - The Rett Syndrome: the recent advances in genetic studies in the USA. AB - The present status of efforts in the USA to understand the genetic basis of the Rett syndrome (RS) is reviewed. Analysis of monozygotic and dizygotic twin data provide compelling support for a genetic mechanism. Similarly, support can be derived from familial cases following maternal lines. Special attention is directed to the X chromosome. Nonrandom X inactivation in the mother of half sisters and the identification of RS girls with translocations involving the X chromosome and separate autosomes have sharpened the focus molecular studies. PMID- 1626623 TI - Neuronal constituents of postural and locomotor control systems and their interactions in cats. AB - Studies in both decerebrate, and intact cats have already established the presence of specific areas in the brainstem that subserve control of posture and locomotion. They are the subthalamic locomotor region (SLR) in the lateral hypothalamic area (LHA), the mesencephalic locomotor region (MLR) in the posterior midbrain, the dorsal tegmental field (DTF) and the ventral tegmental field (VTF) of caudal pons along its midline. These areas can be stimulates either electrically or chemically to induce site-specific changes in posture and locomotor synergies. Our observations indicate that the postural and locomotor synergies are structured in a hierarchy within rostro-caudal axis of the brainstem, and that the command routing through the brainstem relies on interactions with the SLR, the MLR, the DTF area and the VTF area. These results and our concepts for postural and locomotor control and their interactions are discussed with the concepts of command hierarchies for motor control. PMID- 1626624 TI - Electrocortical arousal and spindles on physiological cortico-subcortical interactions. AB - The neuronal mechanisms of electrocortical arousal and sleep spindles were reviewed on the basis of intracellular analyses on the motor cortex in atraumatically maintained encephale isole cat preparations. When arousal is initiated by subcortical afferents from the brainstem, the cortical neurons respond with either excitation (E), inhibition (I), disfacilitation (DF), or disinhibition (DI), in a cascade pattern proceeding from the superficial to deep layers. These neuronal activities on arousal involve DF of the output neurons that may set the subcortical sensorimotor functions in a readiness state for a possible adaptive behavior of animals. This initial transient arousal termed phasic develops soon to the next, more sustained phase termed tonic by the action of other subcortical afferents. The cascade transmissions then occur again, producing E, I, DF, and DI in the cortical neurons but with a reverse laminar pattern proceeding from the deep to superficial layers. These neuronal activities on tonic and arousal deliver the cortical outputs to the subcortical systems that may trigger an orienting or searching behavior of animals in their environment. Sleep spindles also accompany the cascade transmissions that are partly common to those in arousal. Various modes of the cascade transmissions were further examined by applying electric shock stimuli to the cortical surface, the ventrolateral nucleus of the thalamus, and the cerebral peduncle to activate the subcortical afferents converging onto different cortical layers. The combined results from these experiments may imply that the cortico-subcortical interactions in which all the cortical neurons participate with dynamic harmony are instrumental to set a physiological sequence of animal behavior. If these interactions be impaired on the way of normal growth of the brain, as in the case of disorders with the Rett syndrome, many forms of ill adaptation may be brought about by dedifferentiation of sensorimotor functions. PMID- 1626626 TI - The mystery of the Rett syndrome. PMID- 1626625 TI - Early monoaminergic dysfunction. AB - The chemical anatomy of the Rett syndrome and experimental studies concerning early monoaminergic lesions were overviewed. An early monoaminergic dysfunction is a likely occurrence for the mechanism underlying the Rett syndrome. For assessing the alteration of monoamine neuron system, 1) regional vulnerability, 2) age-dependent vulnerability and 3) interaction between the monoamine neuron systems should be considered. PMID- 1626628 TI - Possible lesions of the Rett syndrome: opinions of contributors. PMID- 1626627 TI - Discussion for the Rett Syndrome symposium--the importance of rigorously defining one's level of investigation. PMID- 1626629 TI - Tokyo symposium on the Rett syndrome: neurobiological approach--concluding remarks and epilogue. AB - Based on data presented at the Tokyo Rett Syndrome Symposium, November 1990, actual neurobiological knowledge and interpretations are compiled. The underlying biological concepts, as well as the potential origin of the condition are particularly discussed. PMID- 1626630 TI - Motor symptoms of the Rett syndrome: abnormal muscle tone, posture, locomotion and stereotyped movement. AB - Amongst the motor, mental, cognitive and emotional symptoms of the Rett syndrome (RS) the motor symptoms stand out as the hallmark in analyzing the essential pathophysiology. Summarizing the motor symptoms and searching into the knowledge of relevant basic sciences, this report aims at stressing the pathophysiological basis of RS which we have reported in previous studies. The core motor symptoms of RS consist of two aspects; firstly the unique developmental abnormalities of the discrepancy of crawling and walking and secondly the pathognomonic symptoms which include the abnormal muscle tone, posture, locomotion and stereotyped movement. The deranged crawling reflects the abnormal locomotive function. The primary responsible neuronal structures of the abnormal muscle tone, posture and locomotion are probably in the brainstem. Aberrantly formed neuronal structures responsible for voluntary movements and modulatory factors from the basal ganglia are the pathophysiological basis of the stereotyped movement of RS. Thus the neuronal structures that underlie the clinical characteristics of RS extend broadly from the motor neurons to the higher cortex, but involve the specific neuronal systems. The most important and primary of these specific neuronal systems are thought to be the monoaminergic systems, originating from the brainstem and midbrain. Abnormally deficient noradrenergic, serotonergic and dopaminergic systems result in the abnormal modulation of ontogeny and function of the higher and lower nervous systems. As we have already stressed, this unique putative pathophysiological basis could explain the very striking set of clinical symptoms of RS and their age dependent appearance despite the lack of major specific findings in neuropathology. PMID- 1626631 TI - Electroencephalographical study of the Rett syndrome with special reference to the monorhythmic theta activities in adult patients. AB - The long-term course of the EEG in the Rett syndrome is documented with reference to past studies. The monorhythmic theta activities in the waking state which were characteristically seen in adults with the Rett syndrome were investigated in patients aged between 27 and 28, using auto power spectra. They were often suppressed when the patients were excited or strained. Then the suppression was thought to elevate their conscious levels. The theta activities were often suppressed by calling, but not easily suppressed by other stimuli, especially the somatosensory stimuli of pain and touch. There were also abnormal findings in the ABR and blink reflexes. In the Rett syndrome we, therefore, suspect there are disturbances in the brain stem functions especially in the ascending reticular activating system which is related to elevation of the conscious level. PMID- 1626632 TI - Middle and short latency somatosensory evoked potentials (SEPm, SEPs) in the Rett syndrome: chronological changes of cortical and subcortical involvements. AB - Middle and short latency somatosensory evoked potentials (SEPm, SEPs) were studied in 11 cases of the Rett syndrome (RS) to detect the chronological changes of cortical and subcortical involvements. The cortical N1 (18) latency was significantly delayed in cases above the age of 5 years. Subcortical components up to N16 which are considered to be derived from the thalamus or the upper brainstem were mostly normal in cases under 9 years of age. However, in those over 9 years, the brainstem component P14 and the cervical cord component N13 revealed a delay in latency. The clavicular component N9 and component N11, which is considered to be from the spinal cord entry, were still normal in our cases. These findings suggested that before the age of 9 years, the revealed lesion in SEP is mainly rostral to the thalamus or upper brainstem. With increasing age and disease process, the involvement of the lower brainstem and the spinal cord becomes apparent. Thus, a degenerative process might be suspected. However, the chronological changes of N1 (18) and N13 parallel to normal development seen in RS indicated that the maturational changes were found up to around the age of 5-6 years in the former and 9 years in the latter, though the mean values of these two peak latencies were slightly higher than those in controls as early as the age of 3-4 years. These observations also indicated developmental, probably metabolic, abnormality underlies the pathogenesis of RS and the degenerative process might overlay in the later period of the disease. PMID- 1626633 TI - A review of the respiratory disorder in the Rett syndrome. AB - The characteristics and physiological accompaniments of the respiratory disorder in the Rett syndrome are reviewed and placed in the context of other clinical studies. Events are indicated which may play a part in the occurrence of vacant spells. A scheme is proposed to explain the various manifestations of the Rett syndrome disorder throughout life. The Rett syndrome is viewed as a developmental disorder in which the evolving clinical signs are due to the effects of maturation and aging on an abnormal brain rather than to primary degenerative disease. Thus development elicits preexisting defects which subsequently become clinically manifest. The clinical evidence is suggestive of a genetically determined early defect in central receptive processing which leads to failure of central motor planning with release of extrapyramidal rhythms. PMID- 1626634 TI - Polysomnography in the Rett syndrome. AB - The features of sleep parameters in the Rett syndrome were compared with those in early infantile autism (EIA) and hereditary progressive dystonia with marked diurnal fluctuation (HPD). The sleep-wakefulness cycle and the tonic and phasic components of sleep were evaluated in each disorder, the former was estimated by the day-by-day plot method and the latter two by polysomnography (PSG) following our method. Abnormalities of the sleep-wakefulness cycle were observed in the Rett syndrome and EIA, but in the latter these abnormalities became inapparent with age and improved markedly by correcting the environmental condition and completely by 5-hydroxytriptophan. The latter, if treated early, was followed by improvement of behavior. In the Rett syndrome, however, the abnormalities continued into late childhood to adolescence. In HPD, PSG abnormalities were restricted to the phasic component, which improved completely after levodopa in accordance with the clinical improvement. On the other hand, in the Rett syndrome as well as in EIA both the phasic and tonic components were involved and also the leakage of the components of REM stage into NREM stage was observed. In the Rett syndrome, these abnormalities aggravated with age, with disturbances in % sleep stage, nocturnal variation of tonic and phasic components of sleep and REM-NREM cycles, while in EIA the results of PSGs revealed no such progressions but showed an increase in twitch movement and a lack of normal increase in the number of REMs occurring in short intervals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626635 TI - The Rett syndrome: an introductory overview 1990. AB - The position at the end of 1990 of clinical experiences and research in the Rett syndrome (RS) is summarized. Aspects on clinical and pathogenetic heterogeneity are given. Supports for RS as a developmental neuronal disconnection condition, with early infantile brain growth arrest, are emphasized. In trying to explain origin a two step process is hypothetically suggested: 1) an age dependent genetic deficiency, or transient dysfunction, as a basic predisposing factor; 2) a superimposed trigger factor which might differ in type and between groups of cases. PMID- 1626636 TI - Neurochemistry of the Rett syndrome. AB - The current status of neurochemistry research with respect to the Rett syndrome (RS) is reviewed and correlations developed with the previously described neuropathologic changes. Despite reports of abnormalities in intermediary metabolism and the biogenic amine neurotransmitters, follow-up studies have failed to support any consistent abnormality in either area. In general, the levels of membrane lipid constituents in various brain regions have been similar to control values. New information suggests a disturbance in the ganglioside pattern leading to a reduction in GD1a and GT1b gangliosides in cerebrum and cerebellum. The corresponding reduction of these gangliosides in cerebrospinal fluid, if shown to be specific for RS, could represent an important clue in confirming the clinical diagnosis. Evidence of pervasive growth failure is presented and the current status of the role of beta-endorphins in RS is described. Considerations regarding future directions for research in RS are presented. These strategies include an approach to the fundamental question, namely, the identification of the primary molecular defect. PMID- 1626637 TI - Cerebral blood flow and oxygen metabolism in the Rett syndrome. AB - Positron emission tomography (PET) was performed on six patients with the Rett syndrome and the results were compared with the concurrent clinical status of the patients. The cerebral metabolic rate of oxygen (CMRO2) was low in five patients, and oxygen extraction fraction (OEF) was low in four patients; both had a tendency to decline with advancing age. Although the cause is unknown, it is suggested that impaired oxidative metabolism exists in the Rett syndrome. An analysis of the distribution among brain regions showed that the ratios of values for the frontal cortex to those for the temporal cortex for both the cerebral blood flow (CBF) and CMRO2 were lower than those for the controls, which may indicate the loss of hyperfrontality in the Rett syndrome. Distribution of brain metabolism may be immature in the Rett syndrome. PMID- 1626638 TI - Quantitative magnetic resonance imaging and studies of degenerative diseases of the developing human brain. AB - The Rett syndrome is a progressive disorder which is associated with regression of psychomotor development and precipitous deceleration of brain growth during the first year of life. General histopathological surveys in postmortem specimens have identified degeneration of subpopulations of neurons of the nigrostriatal system but no other evidence of degenerative process. Magnetic resonance imaging based morphometry may usefully guide application of rigorous but demanding quantitative histologic search for evidence of neuronal degeneration. The volumes of the principal set of cortical and nuclear structures of principal interest in the disorder may be measured by currently available MRI-based methods. Optimized levels of precision now allow detection of volumetric changes over time in the same brain of approximately 10% at the 95% confidence level. PMID- 1626639 TI - The neuropathology of the Rett syndrome. AB - The neuropathology of the Rett syndrome is summarized utilizing a format of clinical pathological correlations, describing the pathology at specific anatomic sites which could correlate with the well defined clinical signs and symptoms in the Rett syndrome; decreased head and body size, autism, gait dysfunction, spasticity, movement and breathing disorder. Published reports of altered morphology in the cerebral cortex, basal ganglia, substantia nigra, cerebellum, spinal cord, muscle, nerve, pituitary gland and somatic organs are supplemented by the author's observations. These include studies of dendritic morphology employing Scholl analysis of Golgi preparation, and quantitation of cerebellar Purkinje cells. The possible pathoetiology of the Rett syndrome is considered, particularly, in relation to the ultrastructural demonstration of altered mitochondria and accumulations of lipidic bodies in several tissues. PMID- 1626640 TI - Corticosterone induces rat liver alcohol dehydrogenase mRNA but not enzyme protein or activity. AB - Glucocorticoids induced ADH activity and mRNA 2- to 4-fold in rat hepatoma cells (H4IIE and H4IIEC3), but were reported not to alter ADH activity in rat liver. The failure of corticosteroids to induce ADH may have been due to the short-term treatment of the rats or the dose of steroid used. To reevaluate the effect of glucocorticoids in vivo, we studied animals 4.5 weeks after adrenalectomy so that ADH activity and mRNA should have reached a new steady-state level; the dose of glucocorticoid used was estimated to provide physiological replacement. Male Wistar rats were injected with a single daily dose (10 mg/kg/day) of corticosterone-21-acetate or vehicle subcutaneously for 10 days. Liver extracts were assayed for ADH activity, ADH protein, and ADH mRNA. Nuclei were isolated for nuclear run-on assays. Adrenalectomy did not reduce the activity of ADH in liver. Subsequent corticosterone treatment did not alter ADH enzyme activity, nor did it affect ADH protein levels as analyzed on Western blots. However, Northern blot analysis of ADH mRNA indicated a 2-fold increase in ADH mRNA in the treated animals when the data were normalized to the level of the 28S ribosomal RNA or CHO-B mRNA. The rate of transcription of the ADH gene in nuclei isolated at the end of 10 days of treatment from corticosterone-treated adrenalectomized rats was not statistically different from that in the oil-treated adrenalectomized ones. The disparity between ADH activity and protein levels and the mRNA level may have resulted from other effects of corticosterone, e.g., stimulation of protein degradation or effects on translation. PMID- 1626641 TI - In utero ethanol exposure decreases the biosynthesis of phosphatidylserine in rat pup cerebrum. AB - Phosphatidylserine is enriched in the brain and has been implicated to play a role in regulating neuronal membrane functions. In this study, three experimental protocols were used to examine the effects of in utero ethanol exposure on phosphatidylserine biosynthesis in rat pup brain, namely, (1) assay of the serine base-exchange enzyme activity in brain microsomes, (2) incubation of brain slices with [3H] serine, and (3) incorporation in vivo of [3H]serine into phosphatidylserine as well as serine-related phospholipids in brain. Results from all three protocols point to a decrease in phosphatidylserine biosynthesis in newborn rat pup cerebrum on exposure to ethanol in utero compared with the pair fed controls. When in utero ethanol-exposed pups were nursed by mothers given a chow diet, the differences gradually returned to control levels by 17 days of age. The decrease in phosphatidylserine biosynthesis may be important in explaining some of the neuronal deficits associated with in utero ethanol exposure. PMID- 1626642 TI - Alterations in brain polyribosomal RNA translation and lymphocyte proliferation in prenatal ethanol-exposed rats. AB - The long-term effects of prenatal ethanol exposure on the properties of brain polysomes and the proliferative responses of lymphocytes to mitogenic stimulation in adult offspring were assessed. Female Sprague-Dawley rats either ingested the control or 6.6% ethanol-containing Lieber-DeCarli liquid diet during the 3rd trimester of pregnancy. Controls were age-matched and pair-fed. At 42 to 72 days of age, ethanol effects were evaluated on the (1) polysomal properties in the cerebral hemispheres, cerebellum, and hippocampal regions of the brain after translation in a messenger RNA (mRNA)-dependent rabbit reticulocyte lysate system and (2) immunologic functions of lymphocytes cultured from spleen cells by measuring their responses to mitogenic stimulation. Results showed long-term adverse effects of in utero ethanol exposure on the polysomal RNA translation in each of the three brain regions tested with free polysomal mRNAs affected more than the bound polysomal mRNAs. Of these, the hippocampal region appeared to sustain the most injurious effects. In addition, a suppression of the mitogen induced lymphocyte proliferative responses were present under these conditions. The degree of suppression varied with the specific mitogen used. Data suggest that the ethanol effects on the CNS and lymphocyte proliferation are most possibly irreversible, and in the case of the CNS, a post-translational modification by ethanol is indicated. The reduced lymphocyte responses are suggestive of a possible interference by ethanol of the synthesis of interleukin 2 (IL-2) and/or a reduced binding of IL-2 with its receptor (IL-2 receptors). PMID- 1626643 TI - Effect of ethanol on the release of prostaglandins from ovine fetal brain stem during gestation. AB - Prostaglandins (PGs) have been implicated as mediators of the ethanol-induced suppression of ovine fetal breathing movements (FBM). The objectives of the present study were to determine the ontogeny of the in vitro efflux of PGE2 and 6 keto PGF1 alpha in ovine fetal brain stem during the second half of gestation and to determine the effect of in vitro ethanol exposure on the efflux of these PGs. Ovine fetal brain stem tissue was obtained at mean gestational ages of 80 days (n = 6), 105 days (n = 10), and 135 days (n = 16) by rapid excision following maternal euthanization. Tissue slices (400 microM thickness) were prepared from the lower pons-medulla region of the brain stem. After a 1-hr equilibration period in artificial cerebrospinal fluid, efflux of PGE2 and 6-keto PGF1 alpha in the brain stem was determined using the brain slice-superfusion method, and the PGE2 and 6-keto PGF1 alpha concentrations in the superfusate were determined by specific radioimmunoassay. The mean spontaneous efflux of PGE2 and 6-keto PGF1 alpha expressed as pmol PG/gram wet weight of tissue/5-min collection period was, respectively, 31.9 +/- 4.2 and 26.6 +/- 2.4 at 80 days, 38.3 +/- 5.2 and 29.6 +/- 2.2 at 105 days, and 57.4 +/- 3.1 and 27.1 +/- 1.1 at 135 days of gestation. In vitro exposure to 20, 40, and 80 mM ethanol did not affect PG efflux in the brain stem at 80 and 105 days of gestation. In vitro ethanol exposure decreased PGE2 and 6-keto PGF1 alpha efflux at 135 days of gestation to 36.8 +/- 5.3% and 41.6 +/- 4.3% of spontaneous efflux within 15 min, respectively; this effect of ethanol was not dose-dependent. The data do not support the hypothesis that ethanol increases PG efflux in the ovine fetal brain stem. In view of these findings and the data implicating PGs in the mechanism of ethanol-induced suppression of FBM, it is possible that ethanol acts at either central sites rostral to the brain stem (i.e., upstream CSF) or peripheral sites to increase the synthesis of PGs and their efflux into the systemic circulation, with subsequent transfer to the respiratory control region(s) of the brain stem. PMID- 1626644 TI - Differences in the brain and pituitary beta-endorphin system between the alcohol preferring AA and alcohol-avoiding ANA rats. AB - The content of pro-opiomelanocortin (POMC) mRNA was determined in the hypothalamus, as well as in the anterior and intermediate lobes of the pituitary gland of the alcohol-preferring AA and alcohol-avoiding ANA rats under basal conditions. In addition the content of beta-endorphin-like immunoreactivity (beta EPLIR) was measured in nine brain regions, the anterior and intermediate lobes of the pituitary gland and the serum. The content of beta-EPLIR was significantly higher in the septum and significantly lower in the amygdala, and periaqueductal gray matter of the AA rats, while there was no significant difference between the AA and ANA rats in the arcuate nucleus plus median eminence, nucleus accumbens, caudate, hippocampus, and cortex. HPLC analysis indicated no significant differences in the relative proportions of non-acetyl and acetyl forms of beta endorphin peptides in the hypothalamus, distinct brain regions, and anterior and neurointermediate lobes of the pituitary gland, between the AA and ANA rats. The content of POMC mRNA but not of beta-EPLIR was significantly higher in the hypothalamus and neurointermediate lobe of the AA rats, while the content of both beta-EPLIR and POMC mRNA were significantly higher in the anterior pituitary of the AA than of the ANA rats. Thus, there are genetically determined differences in the pituitary and brain beta-endorphin system between the AA and ANA rats, which may be important in controlling the differences in the voluntary ethanol consumption exhibited by these animals. PMID- 1626645 TI - The rate of ethanol absorption is influenced by corticosterone in long-sleep and short-sleep mice. AB - Ethanol was administered by intragastric (IG) injection and absorption was measured in long-sleep (LS) and short-sleep (SS) mice under various conditions that alter levels of adrenal steroids. In naive mice, LS mice absorbed ethanol more quickly than SS mice. Ethanol absorption was slower in both lines of mice after adrenalectomy (ADX). Short-term inhibition of corticosterone synthesis had no effect on ethanol absorption in either line of mice. The effect of ADX was most pronounced in SS mice at 24 hr after surgery and at 168 hr after surgery in LS mice. Therefore, the effects of various steroid replacements were examined at these times. At 24 hr after ADX, ethanol absorption was replaced to SHAM-operated values in SS mice receiving corticosterone treatments. Likewise, in LS mice at 168 hr after ADX, corticosterone implants reversed the effects of ADX while dexamethasome was ineffective. These results support a role for corticosterone in regulation of gastric ethanol absorption and suggest that the lack of repeatability for pharmacokinetic measures of ethanol absorption and metabolism in previous human and animal studies may relate to environmental impact on stress responses. PMID- 1626646 TI - Effects of ethanol on glucose utilization by cultured mammalian embryos. AB - We have previously observed correlations between placental glucose transfer and growth of fetuses of ethanol (EtOH)-fed and control rats. In the present study, whole mammalian embryos were used to define the interaction of glucose supply and the effects of EtOH on growth and differentiation. Rat embryos were cultured in 75% normal rat serum from day 9.5 to day 11.5 of gestation. EtOH produced dose dependent reductions of embryo protein content (mean +/- SEM = 212 +/- 5, 171 +/- 11, 141 +/- 16, and 113 +/- 9 micrograms/embryo in the presence of 0, 25, 50, and 100 mM EtoH, respectively). Somite number was 25.7 +/- 0.3, 23.4 +/- 0.7, 21.8 +/ 0.7, and 21.1 +/- 0.4 under the same conditions. Exposure to ethanol during the first 24 hr in culture decreased embryo protein content to the same extent as exposure for the entire 48-hr culture period. After 46 hr in culture, control and ethanol-exposed embryos were incubated with 14C-glucose for 2 hr. Ethanol produced dose-dependent reductions of CO2 production, anabolic utilization, lactate release, and total glucose utilization. Glucose supplementation (300 mg/dl) significantly increased embryo protein content and each of these glucose utilization parameters. When glucose utilization was expressed relative to embryo protein content, incorporation of the label into embryonic tissues was significantly reduced by ethanol and increased by glucose supplementation. Embryo protein content correlated closely (r = 0.871, p less than 0.0001) with anabolic glucose utilization. Thus, ethanol directly affects embryo glucose utilization, both as an energy source and as a synthetic substrate, in addition to its effects on placental glucose transfer. PMID- 1626647 TI - Time dependency of IgA nephropathy induction in alcohol ingestion. AB - We investigated the influence of the alcohol ingestion period on the incidence of IgA nephropathy in an animal model. A group of 41 rats received a continuous infusion of liquid diet and alcohol: "alcoholics." A further group of 41 control rats received an isocaloric diet in which the alcohol was replaced by glucose. IgA nephropathy was diagnosed by the presence of intense IgA deposition in the mesangium. At 6 weeks, 60% of the alcoholic rats had IgA nephropathy. The incidence increased until 100% of the alcoholic rats presented the renal disease at 16 weeks. IgA nephropathy was not found in any of the control animals. We conclude that, in this animal model, the incidence of IgA nephropathy is dependent on the time frame of the alcohol ingestion. PMID- 1626648 TI - Ethanol induces marked changes in lymphocyte populations and natural killer cell activity in mice. AB - Treatment of mice in vivo with 5% w/v ethanol given in a liquid diet causes marked changes in spleen, peripheral blood, and thymus lymphocytes. In both the thymus and spleen, there is an acute cellular depletion resulting in a significant decrease in gross tissue size and cell number. In spleen and peripheral blood, the percentage of T lymphocytes is increased relative to B lymphocytes, but the ratio of CD4+/CD8+ T cell sub-populations remains unchanged. Splenic natural killer (NK) cell activity is increased in ethanol-consuming mice, although the percentage of NK1.1+ cells is relatively unchanged. PMID- 1626649 TI - Audiogenic seizure susceptibility and auditory brainstem responses in rats prenatally exposed to alcohol. AB - Rats prenatally exposed to alcohol (0%, 17.5%, or 35% ethanol-derived calories) were tested for audiogenic seizure susceptibility on one of postnatal days 18 to 23, then retested 5 days later. Prenatal alcohol exposure did not influence audiogenic seizure susceptibility or severity. There was, however, a significant increase in seizure incidence on the retest day for all groups, suggesting a priming effect. Auditory brainstem response (ABR) data suggested that prenatal alcohol exposure and acoustic trauma (i.e., exposure to an alarm bell used for eliciting audiogenic seizures) induced measurable sensorineural hearing loss, and that the combined exposure to alcohol and acoustic trauma interacted additively to produce greater hearing loss than either alone. PMID- 1626650 TI - Activation of glycolysis with isoproterenol but not digoxin reverses chronic alcohol depression in hamster hearts. AB - The purpose of this study was to confirm that an agent, which increases diastolic [Ca2+]i, namely digoxin, depresses cardiac performance, mitochondrial activity, and glycolysis in chronic alcohol-treated and myopathic hearts, and that an agent, which lowers diastolic [Ca2+]i, namely isoproterenol, activates cardiac performance, mitochondrial activity, and glycolysis in these animals. Energy levels, glycolysis, mitochondrial activity, hemodynamics, and cAMP were studied in isolated hearts from three groups of animals, i.e., 9-month control hamsters, hamsters given 50% alcohol until 9 months of age, and 6-month-old cardiomyopathic hamsters in heart failure. Isolated hearts were perfused with either a control medium, a medium containing isoproterenol, digoxin, or digoxin + isoproterenol. Measurement of phosphomonoester sugars, and glucose-6-phosphate, were used to assess glycolytic activity. Oxygen consumption was used to analyze mitochondrial activity. All hearts perfused with either isoproterenol or isoproterenol + digoxin showed an increase in developed pressure, rate-pressure-product, and a decrease in end-diastolic pressure. Isoproterenol activated mitochondrial activity and glycolysis in hearts from myopathic and chronic alcohol hamsters. Based on 31P-NMR studies, isoproterenol or isoproterenol + digoxin improved the over-all energy state of hearts from cardiomyopathic hamsters, but not hearts from control and chronic alcohol hamsters. Digoxin alone augmented the rate pressure-product and oxygen consumption in control hearts but not hearts from myopathic and chronic alcohol hamsters. Digoxin caused an increase in end diastolic pressure in myopathic and chronic alcohol hearts but not control hearts. Digoxin depressed glycolysis and worsened the energy state in hearts from cardiomyopathic and chronic alcohol hamsters, but not hearts from control hamsters. In conclusion digoxin, but not isoproterenol nor isoproterenol + digoxin, depressed cardiac performance and glycolysis as well as high energy phosphates in cardiomyopathic and chronic alcohol hearts. Isoproterenol added to digoxin negated the adverse effects of digoxin in cardiomyopathic and chronic alcohol hearts. PMID- 1626651 TI - A recombinant inbred strain analysis of sleep-time responses to several sedative hypnotics. AB - The results of previous studies suggested that the sleep-time differential between long-sleep (LS) and short-sleep (SS) mice decreases for a series of sedative-hypnotic drugs as lipid solubility increases. Using the LS x SS recombinant inbred (RI) strains, we have tested whether this relationship arises because of common genetic influences on the sleep-time responses or was simply a fortuitous difference between LS and SS mice. Mice were sleep-time tested after intraperitoneal injections of a variety of sedative-hypnotic drugs that vary in lipid solubility including alcohols, barbiturates, chloral hydrate, and urethane. Sleep-time values from each of these drugs were compared with ethanol-induced sleep times in the LS x SS RI strains. Significant genetic correlations were observed between ethanol-induced sleep time and those responses elicited by butanol, propanol, and chloral hydrate, but not by pentobarbital or secobarbital. When the partition coefficient (log P) values were compared with the genetic correlations, a significant relationship (r = -0.85) was observed. These data suggest that common genes mediate sedative-hypnotic reactions to ethanol and some drugs resembling it in log P value, and that anesthetic agents with low lipid solubility may be working through different mechanisms than drugs with greater lipid solubilities. PMID- 1626652 TI - Alcohol withdrawal in rats is associated with a marked fall in extraneuronal dopamine. AB - Withdrawal of rats from chronic ethanol (2-5 g/kg, every 6 hr for 6 days) resulted in withdrawal symptomatology and dramatic fall in extracellular dopamine (DA) in the ventral striatum as measured by microdialysis. The changes in DA output paralleled the withdrawal symptomatology and both phenomena were reversed by a challenge ethanol dose (5 g/kg orally). The results suggest that the decrease in DA output may be responsible for the aversive symptoms of withdrawal. PMID- 1626653 TI - Predictors of alcohol abusers' inconsistent self-reports of their drinking and life events. AB - Although considerable research supports the veridicality of alcohol abusers' self reports, all studies find that some proportion of self-reports are inaccurate. Recently, a few studies have examined variables predictive of inaccurate self reports and found considerable intersubject variability. The present study examined predictors of alcohol abusers' inconsistent reports of life events and drinking using test-retest reliability data from two questionnaires. Results indicated that inconsistent self-reports were associated with the type (i.e., objective versus subjective) and amount (i.e., more drinking involvement at the first interview was associated with greater discrepant reports at the second interview) of information to be recalled. It appears that the nature of the questions asked may be as much or more of a contributing factor to inaccurate self-reports as subject or setting factors, especially for individuals who report high levels of alcohol use, for whom special efforts may be necessary to gather valid self-report data. PMID- 1626654 TI - Alterations in EEG amplitude, personality factors, and brain electrical mapping after alpha-theta brainwave training: a controlled case study of an alcoholic in recovery. AB - A controlled case study was conducted of effects of EEG alpha and theta brainwave training with a recovering alcoholic patient who experienced craving and fear of relapse after 18 months of abstinence. Training consisted of six sessions of thermal biofeedback to increase central nervous system (CNS) relaxation. Effects were documented with pretreatment and post-treatment personality testing, 20 channel digitized EEG evaluations both under relaxed conditions and under stress, minute-by-minute physiologic recordings of autonomic and EEG data during each training session, blood pressure, and heart rate indications taken both during relaxation and under stress, and by clinical observation. Results replicated those of a previous controlled study with chronic alcoholic patients not abstinent prior to treatment. New findings include post-treatment indications of more relaxed CNS functioning under stress, and of reduced autonomic activation both during relaxation and under stress. Brain-mapping indications of anxiety associated with painful cold-pressor stimulation were seen only in the pretest readings; at post-test the brain map indicated pain-associated EEG activity in the contralateral somatosensory area, but no apparent anxiety-associated EEG activity. At 4 months post-treatment the patient's wife and colleagues report the patient appears to function in a more relaxed way under the impact of stress, and he reports no longer experiencing craving for alcohol. Overall, support is provided for the possibility that alpha and theta brainwave training may be a useful intervention for the abstinent alcoholic experiencing stress-related craving and fear of relapse. PMID- 1626655 TI - Sedating effects of ethanol and time of drinking. AB - Ethanol (0.5 g/kg) was administered to 12 healthy, normal-sleeping men, aged 21 to 45, at two different times of the day (0900 and 1700 hr). The Multiple Sleep Latency Test (MSLT) was conducted at 1000, 1200, 1400, and 1600 hr in the day drinking condition and at 1800, 2000, 2200, and 2400 hr in the evening drinking condition. On placebo, sleepiness was greater in the daytime testing hours than in the evening, replicating findings on the circadian rhythm of sleepiness/alertness. There was a time of drinking (day versus evening) by ethanol interaction. An ethanol effect on sleep latency was found in the daytime hours, when alertness was relatively low. Ethanol failed to have a significant effect on sleep latency during the evening hours when alertness levels were increasing. Performance on a divided attention task, administered 1 hr postconsumption, was impaired by ethanol consumption, but did not vary as a function of time of drinking (day versus evening). However, at 5 hr postconsumption, mean reaction time on the first 20 min of a 40-min auditory vigilance task was slowed by ethanol to a greater extent after day drinking then after evening drinking. PMID- 1626656 TI - Autism in fetal alcohol syndrome: a report of six cases. AB - This paper reports on six children who all fulfill the criteria for fetal alcohol syndrome and have a history of maternal alcohol abuse during pregnancy, and who also fulfill the criteria for diagnosis of autism. Their behavior and natural history is compared with eight contrast FAS children, of similar ages and functional levels, who were free of autistic behaviors. The autistic FAS children were all moderately or severely retarded. Autistic behavior has not been commonly associated with prenatal alcohol exposure. Clinicians need to be aware of this potential dual diagnosis so that appropriate educational and treatment resources can be employed. PMID- 1626657 TI - Activation, attention, and visuospatial learning in adults with and without a family history of alcoholism. AB - While recent evidence shows visuospatial information processing deficits to be present in chronic alcoholics, it remains unclear whether such deficits are present prior to alcohol abuse in persons at risk for developing alcoholism. If present, it is also unclear whether the information processing mechanisms underlying these deficits are the same in alcoholics and persons at risk for alcoholism. This study investigated visuospatial information processing psychophysiological activation in adults with and without a family history of alcoholism. Thirty matched nonalcoholics served as participants. Fifteen persons were from families in which at least one biologic parent and one other relative had a history of alcoholism. Another group of 15 persons had no family history of alcoholism. In addition to displaying atypical patterns of learning-contingent physiological activation, participants with a family history of alcoholism displayed visuospatial learning that was significantly poorer than persons with no family history of alcoholism. The learning and physiological activation displayed by the participants with a family history of alcoholism were similar to those displayed by previously studied alcoholics using a similar learning task. The data suggest that visuospatial learning deficits may reflect an antecedent to, rather than a consequence of, chronic alcohol abuse. PMID- 1626658 TI - Family history as a predictor of alcohol dependence. AB - The effects of various levels of positive family history of alcoholism on the probability of past year alcohol dependence were investigated using a general population sample of 23,152 drinkers 18 years of age and older. Forty percent reported a positive family history. After adjustment for age, race, gender, and poverty and compared with persons with a negative family history, the odds of alcohol dependence were increased by 45% among persons with alcoholism in second or third degree relatives only, by 86% among those with alcoholism in first degree relatives only, and by 167% among those with alcoholism in first and second or third degree relatives. The effects of family history did not vary among population subgroups as defined by age, race, gender, and poverty. PMID- 1626659 TI - Using adapted short MASTs for assessing parental alcoholism: reliability and validity. AB - In previous research adapted versions of the Short Michigan Alcoholism Screening Test (SMAST) have been employed to assess an individual's father's (F-SMAST) and mother's alcohol abuse (M-SMAST). However, to date psychometric information on these forms has been limited. In order to more broadly assess the psychometric properties of these forms, several critical issues in five related studies were addressed. The samples for the five studies were drawn from a college population at a large midwestern university. Overall, the reliability and validity of the adapted SMASTs appears to be quite good. The F-SMAST demonstrated high reliability (from the standpoint of internal consistency, temporal stability, and reliability across siblings) as well as validity (both in respect to convergence with an interview measure and with father's own report on a parallel instrument). Furthermore, shortening both of these instruments to nine-item versions appears to improve their reliability and validity. For researchers and clinicians interested in assessing parental history of alcoholism, the F-SMAST and M-SMAST would appear to be a reliable and valid paper-and-pencil measure. PMID- 1626660 TI - Sensation seeking, stress reactivity, and alcohol dampening discriminate the density of a family history of alcoholism. AB - Data collected from 95 nonalcoholic men who had either a multigenerational (MFH), unigenerational (UFH), or negative family history (FHN) of alcoholism were subjected to a discriminant function analysis to determine how well a set of variables differentiated between the family history groups. The data-set comprised personality measures (sensation seeking scales, neuroticism, and extroversion), measures of cardiovascular reactivity to unavoidable shock, and measures of the cardiovascular reactivity-dampening effects of alcohol. The discriminant analyses correctly classified 62% of all subjects, 75% of MFH subjects, 47% of UFH subjects, and 63% of FHN subjects. A canonical discriminant function analysis revealed one significant dimension (canonical variable) that differentiated between family history groups. The high density (MFH) family group scored positively on this dimension, while the UFH and FHN groups had negative mean scores on this variable. A MFH of alcoholism was characterized by a pattern of increased sensitivity to the cardiovascular reactivity-dampening effect of alcohol, cardiovascular hyperreactivity to unavoidable shock when sober, and the personality characteristic of experience seeking, which is associated with a desire for novel and unconventional experiences. PMID- 1626661 TI - Alcohol availability and the formal power and resources of state alcohol beverage control agencies. AB - The formal powers and resources of state alcohol beverage control agencies place them in a position to regulate access to alcoholic beverages through restrictions on retail distribution and sales. For example, monopoly states restrict access to spirits, and sometimes wine, by allowing retail sales only through state stores. On the other hand, license and monopoly states share in restricting sales through the use of price posting and fixing provisions. The degree to which these powers are realized in restrictions on alcohol outlets (e.g., licenses) and subsequent alcohol consumption (e.g., sales) was investigated in the current study. In a cross-sectional analysis of data available from 44 alcohol beverage control (ABC) jurisdictions in the United States, it was shown that states with greater restrictions on retail sales had greater resources for the conduct of ABC activities and lower densities of spirit outlets. These states, however, had greater densities of wine and beer outlets. States with greater marketplace restrictions had more resources for ABC enforcement activities and lower outlet densities across all beverage types. Further, supporting the suggestion that availability and demand may be simultaneously related, greater outlet densities were related to greater alcohol consumption (for beer) and greater levels of consumption were related to greater outlet densities (for wine). PMID- 1626662 TI - Resource management. PMID- 1626663 TI - Induction of anaesthesia with propofol using a target-controlled infusion system. AB - Sixty patients premedicated with temazepam were allocated randomly to receive an infusion of propofol designed to achieve and maintain a target blood concentration of 3, 4 or 5 micrograms.ml-1. Induction time was measured from the start of infusion to loss of verbal contact. The success rate of inducing anaesthesia within 3 min of achieving the target concentration was 40% when the predicted target concentration was 3 micrograms.ml-1, 75% when the predicted target was 4 micrograms.ml-1 and 90% when the target was 5 micrograms.ml-1. There were no significant differences between the three groups for time to loss of verbal contact in patients who were induced successfully within 3 min. There were significant reductions in arterial pressure 3 min after achieving the target concentrations within the groups but not between them. The frequency of apnoea and pain on injection was small in all groups. Selecting a target concentration of 5 microgram.ml-1 would successfully induce anaesthesia in the majority of patients premedicated with temazepam without major haemodynamic or respiratory side effects. PMID- 1626664 TI - Ventilatory effects of subarachnoid fentanyl in the elderly. AB - Twenty-eight elderly patients scheduled for urological surgery were randomly assigned to receive, in a double-blind study, subarachnoid hyperbaric bupivacaine 15 mg with 50 micrograms (group A, n = 7), 25 micrograms (group B, n = 7), or 12.5 micrograms (group C, n = 7) of fentanyl or 1 ml of saline (group D, n = 7) in a total volume of 4 ml. The pattern of breathing and the ventilatory response to CO2 were studied before and 90, 150 and 480 min after the subarachnoid injection. In group A, mild pruritus and sedation occurred in five patients, while nausea, vomiting and periodic breathing occurred in two. In group B, mild pruritus and sedation were observed in four patients, while nausea and vomiting occurred in two. No significant differences in minute ventilation, respiratory drive and respiratory timing were observed between the groups. Patients receiving fentanyl 50 micrograms showed a percentual change from baseline values as function of time (slope VE/PE'CO2) significantly below baseline at 90 and 150 min (p less than 0.05). However, the baseline values in this group reverted after 480 min. No side effects were observed in groups C or D. It is concluded that subarachnoid fentanyl 50 micrograms can cause an early respiratory depression and its use as a postoperative analgesic should be avoided in the elderly. PMID- 1626665 TI - Clinical use of a small soda lime canister in a low-flow to-and-fro system. AB - It may be possible to overcome the classical disadvantages of a to-and-fro system by the use of a small soda lime canister. We report our experience of such a system in a series of 13 adult patients requiring mechanical ventilation of the lungs during surgery. The system was found to be convenient to use and the charge of soda lime had sufficient absorptive capacity to last throughout the great majority of surgical cases. Using a fresh gas flow of 1 l.min-1, the ratio of inspired isoflurane concentration to isoflurane vaporizer setting was found to be approximately one half after 10 min of anaesthesia. This ratio was maintained throughout the procedure, except for a few minutes following each change in vaporizer setting. A to-and-fro system using a small soda lime canister is a convenient alternative to the circle system for low-flow anaesthesia. PMID- 1626666 TI - Changes in arterial blood pressure during traction of extra-ocular muscles. A study in rabbits. AB - A significant reflex fall in mean arterial blood pressure from baseline values was observed during extra-ocular muscle traction in rabbits. This effect could be abolished only by retrobulbar block (afferent pathway block) and not by vagotomy, intravenous atropine or glycopyrronium, suggesting that it is distinct from, and independent of, the oculocardiac reflex. We suggest that these reflex changes in blood pressure be known as the 'oculodepressor reflex'. PMID- 1626667 TI - Hyperkalaemic periodic paralysis and anaesthesia. AB - Hyperkalaemic periodic paralysis is the rarer of the two forms of potassium associated familial paralysis. We report a family with hyperkalaemic periodic paralysis with paramyotonia and the anaesthetic management of four affected members. In three of these, paralytic episodes had been precipitated by previous anaesthesia, but this was avoided in the anaesthetics described. We conclude from our experiences that with depletion of potassium before surgery, prevention of carbohydrate depletion, avoidance of potassium-releasing anaesthetic drugs and maintenance of normothermia, patients with hyperkalaemic periodic paralysis can be anaesthetised without complications. We have no evidence that they exhibit abnormal sensitivity to nondepolarising neuromuscular relaxants. PMID- 1626668 TI - Delayed profound respiratory depression after premedication with trimeprazine. AB - Delayed, profound respiratory depression occurred in a 4-year-old boy, who had been premedicated with trimeprazine 4 h after tonsillectomy. This is a rare, but potentially fatal idiosyncratic reaction. PMID- 1626669 TI - Instrumental bronchial tears. AB - Two case reports of bronchial tears following airway instrumentation are presented, one of which resulted in death. Both patients developed pneumothoraces and other complications after attempts had been made under general anaesthesia to insert bronchial stents. It appeared that bronchial tears were made during instrumentation with the stent introducer and these cases demonstrate that great care should be taken when rigid materials, such as plastic guides and bougies, are used blindly in the airway. PMID- 1626670 TI - An evaluation of oxygen delivery using nasal prongs. AB - Oxygen delivery using nasal prongs was assessed using a lung model for spontaneous ventilation. The analogue lung was attached to a manikin, which provided a model of the 'face and pharynx' to which the nasal prongs were applied. Oxygen concentrations were measured in the model trachea at varying fresh gas inflow and peak inspiratory flows. The study demonstrated enormous variability in the both the peak-inspired (26.3-90.0%) and end-expired concentrations (25.2-78.6%) of oxygen delivered to the trachea. There was a regular relationship between the ratio of peak inspiratory flows, expressed over fresh gas inflow and the end-expired oxygen concentrations which could allow estimation of inspired oxygen concentration. PMID- 1626671 TI - A pressure regulator for the cuff of a tracheal tube. AB - A regulator is described for the maintenance of a constant pressure difference above airway pressure during positive pressure ventilation in a cuffed tracheal tube. It comprises a tubular threshold valve which is powered by the anaesthetic gas supply source to a breathing system. The valve is interposed between the anaesthetic gas supply machine and the breathing system creating a pressure differential. The upstream pressure is transmitted to the pilot tube supplying the cuff of a tracheal tube via an upstream connection. The valve is suitable only for breathing systems that require a constant gas supply. The regulator was evaluated during anaesthesia, using a modified Mallinkrodt Hi-Lo jet ventilation tube to obtain simultaneous pressure measurements within the cuff and the lumen of the tracheal tube. A greater pressure was demonstrated in the cuff than in the airway and the two traces were approximately parallel throughout the respiratory cycle. The device should prevent excessive cuff inflation pressure and solves the problem of forgetting to let the cuff down before extubation. PMID- 1626672 TI - An evaluation of the Rapid Infusion System. AB - The performance of the Rapid Infusion System was evaluated in the laboratory. Using a conventional mixture of two units of packed red cells, two units of fresh frozen plasma and 500 ml crystalloid, a single line and a driving pressure of 300 mmHg, the highest flow in our study was 970 ml.min-1 (2.8 mm catheter, no stopcock). With a 1.6 mm venous cannula the measured flow was 640 ml.min-1. Additional diluting of the standard 'blood cocktail' did not add much to the performance of the system. When primed with tap water 21 degrees C (12 degrees C respectively), the fluid at the outlet of the system reached a maximum temperature of 37.8 degrees C (37.4 degrees C) after 6 min at a flow of 400 ml.min-1. At flows higher than 1150 ml.min-1 (priming with 12 degrees C tap water: 800 ml.min-1), the system slowed down to flows of 700 to 1000 ml.min-1 in order to maintain an adequate temperature. We conclude, that the Rapid Infusion System is a valuable tool for situations where a rapid but controlled replacement with warmed blood at rates up to at least 1100 ml.min-1 is needed. The use of large bore intravenous catheters and avoiding additional resistors such as standard 3-way stopcocks is highly recommended. PMID- 1626673 TI - Forces applied during laryngoscopy and their relationship with patient characteristics. Influence of height, weight, age, sex and presence of maxillary incisors. AB - The relationships between patients' height, weight, age, body mass index, gender and presence of maxillary incisors and a series of laryngoscopic factors have been studied. These included the duration of laryngoscopy, maximally applied force, mean applied force and the integral of force over time. There was a positive correlation between height and weight and laryngoscopic factors. Sex and age also showed a positive correlation but these could be explained by differences in height, weight and the presence of maxillary incisors. This latter factor was the dominant patient characteristic influencing the measured laryngoscopic factors. Use of these laryngoscopic factors as a measure of difficulty of laryngoscopy is discussed. PMID- 1626674 TI - The minimum effective dose of lignocaine to prevent injection pain due to propofol in children. AB - In a single-blind study of 100 children aged 1 to 10 years, the minimum effective dose of lignocaine required to prevent injection pain due to propofol was 0.2 mg.kg-1 when veins on the dorsum of the hand were used. This is more than twice the adult value. We concluded that injection pain should not limit the use of propofol in children if an adequate amount of lignocaine is mixed immediately prior to injection. PMID- 1626675 TI - Continuous paravertebral block in children. Initial experience. AB - Continuous paravertebral block has not previously been described for use in children. This study reports the use of this technique in five patients (aged 7 months to 8 years) scheduled for renal surgery or cholecystectomy. The block was not difficult to perform and provided good intra- and postoperative analgesia. Continuous paravertebral block appears to be a promising technique for pain management in children and might prove a valuable addition in the field of paediatric regional anaesthesia. PMID- 1626676 TI - Factors influencing epidural catheter migration. AB - The incidence and amount of migration of epidural catheters was investigated in a prospective randomised study of 153 women who required analgesia in labour. Inward or outward migration occurred in 36% of patients. Inward migration by 1-3 cm occurred in 21 (13.7%) patients and outward migration by 1 cm or more occurred in 34 (22.2%); three (2%) catheters migrated out through the skin. There were significant positive correlations between outward migration and weight, body mass index, and depth of the epidural space. There was no relationship between migration and height, age, intervertebral space used or duration of catheterisation. Problems with epidural block were no more likely in patients in whom migration of 1 cm or more occurred compared with those in whom migration was limited to a maximum of +/- 0.5 cm. However, the pattern of problems was different. All cases of failed epidural block occurred in patients whose epidural catheter migrated outward by 2.5 cm or more. Unilateral blockade was not more likely if migration of 1 cm or more occurred. PMID- 1626677 TI - Perineuronal morphine in intercostal block. AB - In a double-blind, randomised study the potential benefits of combining low-dose morphine with bupivacaine for intercostal nerve blocks for analgesia after biliary surgery were investigated. There was no significant improvement in pain scores or consumption of supplementary analgesics when morphine was added to bupivacaine. This investigation supports the findings of other workers who showed that perineural morphine was ineffective for postoperative pain relief. PMID- 1626678 TI - Haemodynamic stability during general anaesthesia for intra-ocular surgery: the effect of topical oxybuprocaine. AB - Local anaesthesia is frequently used in combination with light general anaesthesia to reduce the reflex responses to surgical stimulation. This combination has not previously been evaluated for intra-ocular surgery. During cataract extraction under general anaesthesia, the effect of topical anaesthesia with oxybuprocaine 0.4% on the pressor response was compared with normal saline in a control group. The simple technique of instilling local anaesthetic drops into the conjunctival sac blocked the pain pathway sufficiently to prevent the pressor response to surgical stimulation (p less than 0.001). Higher inspired concentrations of enflurane were required in the control group to achieve and maintain haemodynamic stability (p less than 0.001). PMID- 1626679 TI - Intravenous regional anaesthesia with 0.5% prilocaine or 0.5% chloroprocaine. A double-blind comparison in volunteers. AB - Ten healthy male volunteers received intravenous regional anaesthesia of the upper limb on two separate occasions using 40 ml of 0.5% prilocaine or 40 ml plain 0.5% chloroprocaine by random allocation. Using a double-blind method, the onset and recovery of sensory block was tested (pinprick) in the four main nerve areas. The onset and recovery of motor block was measured by squeezing a rubber balloon connected to a manometer. The symptoms after deflation of the tourniquet were recorded. Seven volunteers in both groups developed total anaesthesia in 20 min. Complete motor block occurred in 12.3 min with prilocaine and 11.3 min with chloroprocaine. Sensation recovered in all areas in 7.6 min with prilocaine and 10.0 min with chloroprocaine (ns). Motor function recovered in 8.4 and 12.0 min respectively (p less than 0.01). Six volunteers in the chloroprocaine group showed signs of venous irritation and/or antecubital urticaria in the test arm for 30-45 min after the deflation. Four volunteers in the chloroprocaine group had increased in heart rate (greater than 20%) and one of them short periods of junctional rhythm during the first 2 min after tourniquet deflation. Mild, short lived CNS side effects occurred in both groups. PMID- 1626680 TI - The effect of pre-induction glycopyrronium on the haemodynamic response of elderly patients to anaesthesia with propofol. AB - This study investigated whether pretreatment with glycopyrronium can attenuate the hypotension caused by anaesthesia of the elderly with propofol. Twenty elderly patients (77.1 +/- 2.44 years, mean +/- SEM) of ASA physical status 2 or 3 scheduled for elective urological procedures were given glycopyrronium 0 (n = 10) or 5 micrograms.kg-1 (n = 10) in a randomised, double-blind manner, 5 min before induction of anaesthesia with propofol infused at 600 ml.h-1 (average induction dose 1.7 +/- 0.06 mg.kg-1, mean +/- SEM) followed by maintenance with a propofol infusion at 10 mg.kg-1.h-1. Although glycopyrronium significantly increased heart rate (p less than 0.01, ANOVA), the decrease in blood pressure 2 and 5 min after induction was similar in both groups. The study had a power of 80% to detect a 20 mmHg difference in systolic arterial pressure between treatment groups with p less than 0.05. PMID- 1626681 TI - Predicting difficult intubation. What factors influence the thyromental distance? PMID- 1626682 TI - The variable deadspace is not necessary. PMID- 1626683 TI - Anaesthetic death of a child with a cold. PMID- 1626684 TI - Manual ventilation and the Humphrey ADE breathing systems. PMID- 1626685 TI - Suprascapular nerve block. New indications and a safer technique. PMID- 1626686 TI - Intra-articular morphine for the management of frozen shoulder. PMID- 1626687 TI - Potential hazard with the M&IE Carden Ventmasta ventilator. PMID- 1626688 TI - A badly fitting tray. PMID- 1626689 TI - Blood reflux, central venous cannulation and right-sided haemothorax. PMID- 1626690 TI - Reversal of prolonged suxamethonium apnoea. PMID- 1626691 TI - Epidural infusion of bupivacaine and diamorphine for postoperative analgesia on surgical wards. PMID- 1626692 TI - Fibreoptic laryngoscopy as a method of assessing the risk of airway obstruction following laryngeal mask airway insertion. PMID- 1626693 TI - Decorative hairbands--an unusual cause of difficult intubation. PMID- 1626695 TI - Change to the TVX transducer cartridge. PMID- 1626694 TI - Patient misunderstanding. PMID- 1626696 TI - Can calcium channel blockers prior to tracheal intubation prevent myocardial ischaemia. PMID- 1626697 TI - Blease Manley 4 ventilator and PEEP. PMID- 1626698 TI - Maximal respiratory pressure measurement. PMID- 1626699 TI - Determination of protamine dose. PMID- 1626700 TI - More on automatic cardioverter-defibrillators. PMID- 1626701 TI - Problem with a laryngeal mask airway. PMID- 1626702 TI - Use of 15 mm tubing with the Humphrey ADE breathing system. PMID- 1626703 TI - Eliminating pollution in paediatric and dental anaesthesia. PMID- 1626704 TI - Planar chromatography. PMID- 1626705 TI - Liquid chromatography: theory and methodology. PMID- 1626706 TI - Size exclusion chromatography. PMID- 1626708 TI - Dynamic electrochemistry: methodology and application. PMID- 1626707 TI - Mass spectrometry. PMID- 1626709 TI - Cytochemical localization of dipeptidyl peptidase II activity in rat incisor tooth ameloblasts. AB - Dipeptidyl peptidase II (DPP II), E.C. 3.4.14.2, a serine class endopeptidase, is widely used as a lysosomal marker in cytochemical studies. To date most ultrastructural studies of ameloblasts use the presence of acid phosphatase activity to identify cellular organelles to be lysosomal. Using decalcified rat mandibles, with kidney tissue as a positive control, DPP II activity, was assessed with specific substrate Lysyl-alanine-4-methoxy-2-naphthylamide in ameloblasts at an ultrastructural level. Reaction product (RP) indicative of DPP II activity was observed only within lysosome-like organelles. These RP-labelled organelles were only localized in the supra- or para-nuclear regions of the ameloblasts, which corresponds with previous studies using acid phosphatase cytochemistry. However, in contrast with these studies, RP was not detected in the distal region of the ameloblasts, viz., in the Tomes' processes of the secretory ameloblasts or near the ruffled border in the maturation ameloblasts. The transitional ameloblasts were notable for the intensity of staining of their RP-labelled organelles. We propose that DPP II may have a role in programmed cell death which is thought to occur in this transition zone. Biochemical analysis of rat incisor enamel organ homogenates, indicated tissue fixation resulted in an 82% reduction in DPP II activity, although the specific activity of DPP II was not affected. PMID- 1626710 TI - Chondroclasts and endothelial cells collaborate in the process of cartilage resorption. AB - The condylar cartilage of the young rat is a major growth center of the craniofacial complex. Differences between the mechanism that results in bone formation from growth centers in the epiphyseal plates of long bones are dictated primarily by the different character of the mineralization of the cartilage. In this ultrastructural study we demonstrate that the terminal hypertrophic chondrocytes undergo apoptosis and disintegration while simultaneously chondroclasts dissolve gaps in the calcified cartilage that engulfs them. The latter are also phagocytizing debris of the chondrocytes. The chondroclasts are intimately followed by tube-forming endothelial cells that most probably coalesce to create extensions of the invading capillaries into the evacuated lacunae. The chondroclasts have ultrastructural features similar to osteoclasts. They are multinucleate, are rich in mitochondria and vacuoles, form clear zones that adhere to the spicules of the calcified cartilage, and also form a sort of ruffled border. The latter is not as elaborate and orderly arranged as is known from osteoclasts. The capillaries that follow orient the stroma cells to the evacuated lacunae and, together with the calcified cartilaginous scaffold, supply the adequate environmental conditions for the stroma cells to differentiate into osteoblasts and to build up trabecular bone. PMID- 1626711 TI - Changes in the apical microfilaments of rat uterine epithelial cells in response to estradiol and progesterone. AB - This study investigates the interaction of hormones and the cytoskeleton within the apical cytoplasm of uterine epithelial cells of the rat. The effects of the hormones estradiol-17 beta and progesterone on the microfilament configuration were studied using myosin subfragment 1 (S1) decoration of actin microfilaments (MF) and transmission electron microscopy. In control ovariectomized animals, a sparse MF distribution was found in the apical cytoplasm underlying short microvilli with S1-decorated core MF. Hormone treatment experiments consisted of injecting ovariectomized rats with either progesterone or estradiol-17 beta. For the study of the MF configuration accompanying an apical surface primed for blastocyst receptivity, progesterone treatment was immediately followed by a single dose of estradiol-17 beta. The long, regular microvilli associated with estradiol only treatment contained bundled, decorated MF with tightly bundled rootlets. Progesterone alone produced numerous short microvilli with decorated core bundle MF and pronounced rootlets that frequently appeared splayed. The irregular microvilli and luminal surface of the uterine epithelial cells associated with the receptivity hormone sequence contained variable MF configurations, including MF bundles, networks, and areas with a "felted" appearance. The results show that the various hormone regimes produce characteristically different MF configurations and that this component of the cytoskeleton appears to be under the control of a delicate hormone balance within these uterine cells. The responses of uterine MF to specific regimes of steroid hormones used in this study are not only important for the understanding of the mechanisms at work during early pregnancy, but also contribute to the body of knowledge concerning the ways in which hormones in general effect the cytoskeleton of target cells. PMID- 1626712 TI - Reinitiation of gonocyte mitosis and movement of gonocytes to the basement membrane in testes of newborn rats in vivo and in vitro. AB - Movement of postnatal gonocytes to the periphery of the seminiferous cord, where they contact the basement membrane, and resumption of mitosis by these previously quiescent cells are likely to be critically important in establishing spermatogenesis in neonatal rats. We used several approaches both in vivo and in vitro to determine precisely when each of these two events begins, to study their temporal relationship to each other, to determine whether gonocyte division is a prerequisite for relocation or vice versa, and to probe the source of factors initiating and/or regulating these events. Both light and electron microscopy were used to determine that the first gonocytes make contact with the basement membrane on postnatal day 4, while quantitative autoradiography following 3H thymidine administration in vivo indicated that the first gonocytes to re initiate cell division do so one day earlier, on day 3, and that the percentage of gonocytes dividing remains at a stable level through day 5. Moreover, we organ cultured neonatal testes from birth onwards in the presence of defined, serum- and hormone-free medium and determined that both proliferation and relocation of gonocytes begin and continue in vitro as in vivo. This observation argues against involvement of extratesticular factors in stimulating gonocyte relocation and division, and points to the testis itself as the most likely source of agent(s) regulating postnatal maturation of these cells. In other, similar incubations we included 3H-thymidine for varying periods of time to label either those gonocytes that are the first to divide or all gonocytes that divide during the first 48 hr of culture. From these studies, we confirmed that the first gonocytes to divide do so while separated from the basement membrane and found that, although some cells divide before moving peripherally, others do not. PMID- 1626713 TI - Evidence that hepatocytes can phagocytize exogenous substances. AB - Although the phagocytic action of Kupffer cells is well known, such a phenomenon has not been well documented for hepatocytes. Following the injection of a suspension of egg lecithin-coated silicon particles (0.5-1.5 microns in diameter) into the portal vein of rats, Kupffer cells showed minimal phagocytotic action, which was in contrast to the hepatocytes which displayed numerous phagocytized silicon particles. By comparison, when noncoated silicon particles of the same diameter as those that were coated were injected into the portal vein, the opposite observation was made. There was no uniformity in the ability of the hepatocytes to phagocytize either coated or noncoated particles from one lobule to another. Some showed active phagocytosis, while in others no evidence of such a process was observed. These data provide strong evidence for the selective phagocytic action of liver hepatocytes. PMID- 1626714 TI - Forms of lung lymphatics: a scanning electron microscopic study of casts. AB - In a recent study, rats given monocrotaline underwent angiogenesis on their pleural surfaces. The rats also had novel structures in their bronchovascular bundles that were detected by scanning electron microscopy of vascular casts. These vessels could have been either new blood capillaries or dilated lymphatic capillaries. To determine if these structures were lymphatics or new blood vessels, specimens from animals that were undergoing angiogenesis were compared to those that were not. Finding similar structures in normal animals would imply that they were lymphatic. The second purpose of this work was to describe the three-dimensional anatomy of the lymphatics of the lung. Cast lymphatics were found in most lungs with edema or angiogenesis, but were rare in other conditions. The vascular structures in question were found in animals not undergoing angiogenesis and were, therefore, lymphatic. Additionally, scanning electron microscopy of casts showed several distinct forms of lymphatics in the lung. Prelymphatics are tissues planes beneath the pleura and around bronchovascular structures. They join reservoir, conduit or tubulo-saccular lymphatics. Reservoir lymphatics are broad ribbon-like structures with textured surfaces and small laterally branching pouches. They occur on the pleural surface, are closely linked with prelymphatics, and join conduit lymphatics. Conduit lymphatics are tubular structures that may contain valves, twist and go great distances without accepting tributaries. On the pleural surface, they may wind around blood vessels and vary greatly in diameter. Sacculo-tubular lymphatics surround arteries, veins and bronchioles. They have thin walls with wide saccular segments. They may be so dense that they form cylinders around the vessels or airways. Different forms of lung lymphatics suggest different function and potential. PMID- 1626715 TI - Scanning and transmission electron microscopy of venous sphincters in the rat lung. AB - The rat pulmonary microvasculature was studied using scanning and transmission electron microscopy of vascular corrosion casts and tissue sections. Special emphasis was placed on small pulmonary venous vessels. The shape of vascular casts was analyzed and interpreted concerning the wall composition of corresponding vessels studied in tissue sections. On the casts of pulmonary venules and small pulmonary veins, narrow or wider annular constrictions were regularly observed. Within these constrictions, marks of circularly running grooves were seen as an additional structural detail, which obviously mimic impressions of single or grouped smooth muscle cells. The depth of the constrictions varies; it may be more or less pronounced, occasionally narrowing down the luminal diameter to approximately 50%. These constrictions are caused by muscular sphincters. In tissue sections of small pulmonary veins, sphincter regions were identified as abruptly appearing single or grouped true smooth muscle cells. Smooth muscle cells may be arranged side by side in a group or bundle or even staked in two or three layers. Between the sphincter regions, the venous wall consists merely of endothelium and an accompanying connective tissue layer. The smooth muscle cells of a sphincter are regularly positioned between endothelial layer and elastic lamina. The smooth muscle cells next to the endothelium form myoendothelial junctions. Autonomic nerves near the sphincters were never seen. The venous sphincters described are suggested to be effective devices involved in blood flow regulation. Blood-borne substances or local tissue hormones might govern sphincter function. PMID- 1626716 TI - Immunohistological characterization of proximal colonic lymphoid tissue in the rat. AB - Proximal colonic lymphoid tissue (PCLT) is a lymphoid structure located in the proximal colon of the mouse and the rat. In the present investigation we studied the immunomorphology and cytology of PCLT in the rat. We also studied sites of lymphocyte proliferation using the BrdU-anti BrdU technique. Results demonstrated no evident phenotypical differences between the lymphocyte populations of PCLT and either jejunal or ileal Peyer's patches (PP). The majority of the lymphocytes within PCLT were B cells localized in follicles, which were separated from each other by interfollicular T cell areas. Germinal centers (GC), containing ED5+ follicular dendritic cells, are found within PCLT follicles. The T cell areas contained both MHC Class II+ interdigitating cells and high endothelial venules. Studies using BrdU-anti BrdU indicated that lymphocyte proliferation within PCLT takes place mainly in germinal centers. Together the data show that the organization, lymphoid constituents, and sites of lymphocyte production are very similar in PCLT and PP. We therefore conclude that PCLT in the rat is not a Bursa equivalent, but more likely a PP with some special characteristics. PMID- 1626717 TI - Follicle-associated epithelium and medullary epithelial tissue of the bursa of fabricius are two different compartments. AB - The bursae of Fabricius from the chicken and turkey were studied by light and electron microscopy and immunohistochemical methods. The study focused on the relationship of follicle-associated epithelium to the medulla. The follicle associated epithelium was supported by 3 to 5 layers of stratified epithelial cells which were a continuation of the corticomedullary epithelial cells. The follicle-associated epithelium consisted of M cells and scattered secretory dendritic cells. The network of the reticular epithelial cells of the medulla was filled with secretory dendritic cells, B cells, and a few T cells and macrophages. The cellular content of the follicle-associated epithelium and the medulla suggested that they were different cellular compartments. Communication between the follicle associated epithelium and medullary epithelial compartment occurred through the supporting cells of the follicle-associated epithelium. When the supporting layers of the follicle-associated epithelium infolded into the medulla, they formed lamellated epithelial bodies similar to the thymic Hassall bodies. The lamellated bodies enclosed secretory dendritic cells but not lymphocytes. The infolding of supporting cells varied from follicle to follicle. The asynchronization of infolding contributed to heterogeneity of follicle composition. Follicle heterogeneity was demonstrated by differences in reactivity with a battery of monoclonal antibodies. PMID- 1626718 TI - Demonstration of amelogenin in the enamel-free cusps of rat molar tooth germs: immunofluorescent and immunoelectron microscopic studies. AB - The enamel-free cusps of 1-4 day-old rat mandibular first molars were investigated using the monoclonal antibody En3 against rat amelogenin at light and electron microscopic levels in order to clarify whether the enamel-free cusp is virtually devoid of enamel. At 1 day after birth, there were presecretory ameloblast-like cells (PALCs), which were short and were not polarized, at the cusp tips. They were close to the outer enamel epithelium. Hematoxylin positive enamel matrix was not distinctly observed in the enamel-free cusp by light microscopy, but almost continuous immunofluorescence for amelogenin was detected at the interface between PALCs and dentin. The penetration of immunopositive material toward the dental pulp was also observed in the enamel-free cusp. At 4 day after birth, both in the frontal section and in the horizontal section, almost continuous immunofluorescence was recognized at the interface between PALCs and dentin in the enamel-free cusp. The penetration of amelogenin toward the dental pulp was not seen in the enamel-free cusp. By immunoelectron microscopy, immunolabelling was recognized in the Golgi apparatus of PALCs, in a layer of amorphous material at the interface between PALCs and dentin, and in stippled material-like substance in the intercellular space between PALCs. Although no basement membrane was observed beneath PALCs, they did not have Tomes' processes. These investigations suggest that PALCs in the enamel-free cusp differentiate into the secretory cells and that they can synthesize and secrete the amorphous material containing amelogenin at the interface between PALCs and dentin. The penetration of amelogenin toward the dental pulp might play a role in the interaction between PALCs and odontoblasts in the enamel-free cusp and/or the initiation of mineralization of predentin. PMID- 1626719 TI - Postnatal development of the harderian gland in the Syrian golden hamster (Mesocricetus auratus): a light and electron microscopic study. AB - The main objective of the present investigation was to study the morphological and chronological aspects of the development of the Harderian gland in the Syrian golden hamster. Tissues were obtained from male and female hamsters at days 1,3,5,7,10,12,15,17,20,27,37,46, and 90 after birth and processed for light and transmission electron microscopy. The present observations indicate that a well defined temporal sequence in microscopic and ultrastructural modification is recognizable in the development of the hamster Harderian gland. Four stages of development were proposed. Between days 1-5 (first stage), the gland shows characteristics of an immature structure. The glandular cells contain many free ribosomes, few and small organelles, and large irregular-shape nuclei. Between days 7-17 (second stage), there is a marked increase of organelles involved in synthesis and secretion. The gland begins the secretion of lipids and porphyrins, but no morphological differences between male and female glands are observed. Between days 20-36 (third stage), the morphological differences between the two sexes appear and progressively develop. In 45-day-old hamsters, the Harderian gland possesses the structural characteristics of adult glands, and further developmental changes are essentially quantitative in nature (fourth stage). At all stages of development, the population of secretory cells has a uniform appearance. The morphological results are discussed as well as the possible relationship of this temporal sequence with hormonal changes. PMID- 1626720 TI - Inhibition of epibranchial placode-derived ganglia in the developing rat by bisdiamine. AB - Although bisdiamine has been shown to affect the development of mammals, its effect on the nervous system has gone largely unrecognized. In the present study, rats were given bisdiamine by gavage on days 9 and 10 of pregnancy. They were sacrificed at intervals and the fetuses were prepared for study of serial sections stained with hematoxylin and eosin, or by immunohistochemical reaction with HNK-1 monoclonal antibody. HNK-1 reacted strongly with the nervous system, allowing precise analysis of the components and their relationships. Controls receiving no bisdiamine were prepared and studied in parallel with the experimental fetuses. Administration of bisdiamine inhibited development of the petrosal and nodose ganglia, altered associations of the glossopharyngeal, vagus, and hypoglossal nerves, and inhibited contributions of vagal nerve fibers to the developing enteric system. The proximal ganglia of the glossopharyngeal and vagus nerves developed normally. It is concluded that bisdiamine affects, directly or indirectly, the differentiation of nervous components derived from the epibranchial placodes. It seems likely that these placode-derived components serve as pioneer neurons in establishing the pathway for the posteriorly extending trunks of the glossopharyngeal and vagus nerves. The early changes in congenital conditions such as the DiGeorge syndrome may not be limited to alterations in neural crest derivatives. It may be worthwhile to investigate more closely whether there are alterations in the nervous system associated with these syndromes. PMID- 1626721 TI - Selective lectin-binding sites of primordial germ cells in chick and quail embryos. AB - To ascertain the histochemical characteristics of surface carbohydrates on avian primordial germ cells (PGC), we examined the distribution of binding sites for several biotinylated lectins in chick and quail embryos. Some binding sites were detected almost selectively with PGC but not with other embryonic sites. Of these, lectin from Sojanum tuberosum (STA) reacted with PGC in both avian species, whereas lectin from Wistaria floribunda (WFA) and Griffonia simplicifolia II (GS-II) reacted in the quail and the chick, respectively. The binding site for STA was found at the cell surface and cytoplasm of the PGC from their initial appearance in the germinal crescent through migration to sexually indifferent gonads, whereas the WFA reaction was seen at stages before and during migration. These reactivities showed most intensely on the surface of PGC at the peak of their migration. In contrast, GS-II binding site was restricted to the cytoplasm, and its distribution was similar to that of the periodic acid-Schiff (PAS)-positive glycogen granules in chick PGC. These results suggest that some selective binding sites on the PGC surface play a significant role in their migration and show that lectins STA, WFA, and GS-II can be used as probes for identification of the avian PGC. PMID- 1626722 TI - Stratificational relationship among the main nerves from the dorsal division of the sacral plexus and the innervation of the piriformis. AB - In order to comprehend more completely the morphology of the nerves to the piriformis, it is necessary to obtain a detailed understanding of the relationship of the origin and the course of these nerves from the dorsal division of the sacral plexus, with reference to the superior and inferior gluteal nerves. Twelve of seven human pelvic halves were carefully dissected in order to examine the origins of the nerves from the dorsal division of the sacral plexus. Six of these pelvic halves were further dissected under a stereomicroscope to examine the nerves to the piriformis. 1. The origin of the superior gluteal nerve was more proximal and dorsal in the sacral plexus than that of the inferior gluteal nerve. 2. The superior gluteal nerve consisted of a thick cranial part and a thin caudal part; the former continued as the inferior branch of the nerve, and the latter, the superior branch. The cranial and caudal parts crossed before reaching the glutei medius and minimus. 3. The nerves to the piriformis arose from three main nerves from the dorsal division of the sacral plexus: 1) the caudalmost root of the superior gluteal nerve, 2) the caudal roots of the inferior gluteal nerve and 3) the common peroneal nerve. Considering the stratificational relationship among the main nerves from the dorsal division of the sacral plexus, the piriformis appears to be composed of parts from different muscle layers. PMID- 1626723 TI - Arteriographic study of the rabbit lower limb. AB - The rabbit hind limb has been used extensively as an orthopaedic model in the investigation of fracture pathology and healing and the effects of vascular abnormalities. However, a detailed description of the normal arterial supply appears to be absent from the literature. A study of the entire arterial vasculature has been undertaken using a lead oxide injection technique developed for this and other orthopaedic studies. This technique has proved reliable and inexpensive, giving high-quality arteriography, which is easily interpreted. Accurate description of the arterial anatomy is possible without the need for repeated dissection. The rabbit lower limb shows some interesting variations in blood supply, particularly below the knee. The foot has three distinct patterns of blood supply, depending on the presence or absence of the peroneal artery and the degree of dominance of the dorsalis pedis artery. This arrangement has not previously been described and differs from the situation in other mammals. The arteriographic technique and the anatomical description have allowed the interpretation of changes occurring in the vasculature after injury in a fracture model. PMID- 1626724 TI - Plastic embedding procedure for 15 microns sections of large undecalcified tissue blocks. AB - A method is described that produces sections (15 microns) of large specimens (with dimensions up to 140 x 100 x 200 mm). They are suitable for comparison to CT images of that specimen and can be used as a basis for three-dimensional reconstructions. Frozen unfixed parts of the human body are embedded in polyurethane and scanned with CT. Undecalcified slices, 6 mm thick, of these specimens are cut with a bandsaw. These slices are successfully embedded in polyester resin by means of fixation, dehydration, and subsequent impregnation with this resin. Sections of 15 microns are obtained by cutting the trimmed and sandpapered polyester blocks with an LKB multirange microtome. They are collected on adhesive tape and stained according to Weigert-Azan, sealed between adhesive acetate sheets and photographed on colour slide film. As an example photographs of sections of the human elbow and lumbar spine region are presented. PMID- 1626725 TI - [Arteriovenous fistulae of posttraumatic origin: apropos 7 cases]. AB - We present our experience with arterio-venous traumatic fistulas. Seven cases, between 6 patients are reviewed. Respective etiologies were: 4 cases after an accidental traumatism, 2 cases produced by iatrogenicity and 1 case of idiopathic etiology. Respective localizations were: 6 cases at lower limbs (85.7%) and one case at cervical column (14.2%). All patients underwent surgical treatment. There was any case of mortality and treatment results were satisfactory in all cases. Patients were followed and, up to now, no recidives have been registered. follow time ranged from 1.5 to more than 6 years. PMID- 1626726 TI - [Cholesterol embolism: an infrequent cause of ischemic ulcers of the lower extremities]. AB - A case of cholesterol embolism with digital ulcerations is reported. Pathologic anatomy, Radiologic images, symptomatology and treatment of such pathology are discussed. PMID- 1626727 TI - [Simultaneous coronary and carotid surgeries]. AB - Two patients with severe coronary artery disease and significant stenosis of the left internal carotid artery were operated upon. A combined or simultaneous operation was performed in both, carotid endarterectomy plus coronary artery bypass surgery was performed. The patients are symptoms-free after the operation and with evidence of satisfactory reconstruction in the carotid and coronary arteries. A review of the topic simultaneous revascularization of the carotids and coronary arteries in presented. PMID- 1626728 TI - [Acute arterial thrombosis of the extremity in pseudoxanthoma elasticum]. AB - We report a case of a patient with an elastic pseudoxanthoma (PXE) who presented an acute ischaemia at the left lower limb. The cause of such ischaemia was a thrombosis into the iliac and femoropopliteal arteries. Patient underwent a surgical procedure. The arteriopathy associated with a PXE rarely cause an arterial major occlusion. We did not found a case of acute arterial thrombotic ischaemia and PXE, treated with direct arterial revascularization in the reviewed literature. PMID- 1626729 TI - [Postural physiotherapy: a possible conservative treatment of the thoracic outlet syndrome]. AB - A physiotherapy treatment protocol of "thoracic outlet syndrome" is presented. This treatment is based on the correction positional and not on the reinforcement and developing of determinate muscular groups. Treatment includes 10 exercises, which have to be progressively practiced during each seance. Twenty patients were included into the assay, and they have no signs of their Syndrome by the end of the study. Authors conclude that positional physiotherapy treatment is effective on cases of "thoracic outlet syndrome" without neurovascular complications. PMID- 1626730 TI - [The study of arteriogenic erectile impotence by noninvasive methods]. AB - With the development of noninvasive haemodynamic methods, recognition of arterial insufficiency signs is possible also in cases in which, in old times, we just could suspect a psychogenic cause. Although this advance, discrimination permitted by this method can be improved. Eighty-eight supposed healty patients and eighty-four patients with arteriogenic erectile impotency (tested by arteriography) were included into an study, which results are presented in here. Analysis made, avoided the effect of envelleiment on haemodynamic parameters interpretation. For identification of patients which obstructive arterial defect can be cause of sexual disfunction, combination of systolic pressure determination and arterial flow velocity curves (by Doppler ultrasonography) is proposed. We recommend this method as a part of the multifactorial examen required by such type of patients. PMID- 1626731 TI - The Simon nitinol filter: evaluation by MR and ultrasound. AB - In this prospective blinded study of inferior vena caval (IVC) patency, 18 patients underwent 25 duplex ultrasound (US) and magnetic resonance (MR) angiography examinations over an eight-month period following Simon nitinol filter placement. Clinical examination for lower extremity venous stasis and plain abdominal radiography were also performed. Twenty-three of 24 MR examinations and 11 of 24 US examinations were judged technically adequate by the blinded observers. One technically adequate US exam was false positive for intraluminal caval thrombus. Thirteen technically inadequate US examinations missed 3 complete caval occlusions and 2 partial occlusions. MR identified all patients with complete or partial caval occlusion. The authors conclude that duplex US reliably confirms IVC patency only when strict criteria for technical adequacy and interpretation are met (good visualization of filter and IVC above and below filter). MR, although expensive, more reliably identifies nonoccluding intraluminal thrombus and caval occlusion. It should be the noninvasive study of choice in symptomatic patients with venous stasis and patients with recurrent pulmonary emboli. PMID- 1626732 TI - Effect of pentoxifylline on treatment of lower limb ulcers in patients with thalassemia major. AB - The possible healing effect of deferoxamine and pentoxifylline on persisting lower limb ulcers was studied in 51 patients with thalassemia major. The results indicated that the regular use of deferoxamine at an intravenous dose of 20 mg/kg did not affect the healing progress and the recurrence rate of these ulcers significantly. On the contrary, the oral administration of pentoxifylline at a dose of 1,200 mg daily during the ulcer's healing time and at a low long-term maintenance dose of 400 mg daily during the ulcer-free intervals improved their healing ability impressively and diminished their recurrence rate significantly. PMID- 1626733 TI - Measuring ankle systolic blood pressure: validation of the Dinamap 1846 SX. AB - Clinical and epidemiologic situations requiring repeated measurements of blood pressure in the lower extremity are increasingly incorporating automated measurement devices; however, no device has been validated adequately for ankle blood pressure. This study evaluates the Dinamap 1846 SX against Doppler ultrasound in determining ankle systolic blood pressure (SBP) and compares a parallel with contour wrapping technique for applying the blood pressure cuff. Ankle SBP was measured on 71 adult volunteers by both devices simultaneously, for each cuff wrap. Averages of three readings were compared to evaluate Dinamap versus Doppler SBP estimates and to assess any cuff wrap effect. Multiple linear regression was used to assess potential effect modifiers. Instrument differences (Dinamap minus Doppler) for the parallel wrap (95% confidence intervals in parenthesis) were -1.5 mmHg (-3.1, 0.0) and -3.9 mmHg (-5.6, -2.2) for the contour wrap. Wrap effect differences (contour minus parallel) for the Doppler were -4.9 mmHg (-6.3, -3.5) and -7.2 mmHg (-8.7, -5.8) for the Dinamap. Degree of ankle taper was a strong modifier of cuff effect for the Dinamap but not for the Doppler: adjusted cuff effect with the Dinamap ranged from -3 to -10 mmHg. Measurement precision (within-person reproducibility, measured by within-person standard deviation [sigma 2] and reliability coefficient [R]) was higher for the Dinamap than the Doppler technique, lowest for the parallel wrap and Doppler configuration (sigma 2 = 5.4 mmHg, R = 0.88) and greatest for the contour wrap and Dinamap (sigma 2 = 4.0 mmHg, R = 0.94). In conclusion, cuff-wrapping technique can generate SBP differences of greater magnitude than instrument differences. Conditional on the use of the contour wrap, and by virtue of its high repeatability and ease of operation, the Dinamap is a useful tool for epidemiologic study and the clinical assessment of peripheral arterial disease. PMID- 1626734 TI - Measurement of lymphatic flow variation by noninvasive method cases of lymphedema. AB - The purpose of this study was to measure the variations of lymphatic flow. A noninvasive isotopic method was used to achieve a functional exploration of lymphatic circulation. Fifteen subjects were used in the study: 10 healthy subjects and 5 patients with lower extremity lymphedema. A first subcutaneous injection of technetium 99m rhenium sulfate (99mTc) was performed in the first interdigital space of both feet. The radioactivity was recorded in two places: the first one on the inguinal site by a gamma camera; the second, below the first, on the precordial site by a multichannel analyzer. With the two types of recording procedures, it was possible to obtain a curve that showed the amount of radioactivity in relation to time. In order to obtain a muscular activity fifty five minutes after the injection, each subject or patient spent ten minutes on an ergometric bike. A second subcutaneous injection was performed one week later, but prior to the injection, the subject or patient took orally 1800 mg of heptaminol adenosine phosphate (HAP) per day for three days. The radioactivity recording was made under the same conditions as with the muscular activity. The statistical results of the experiment without treatment on the two types of recording show that in the healthy subjects the amount of radioactivity increased during muscular activity. Moreover, the treatment indicated higher radioactivity values, which remained at a higher level. However, the muscular activity performed by a patient was unable to increase the radioactivity. On the other hand, the drug gave radioactivity values that were higher than the previous values of the first curve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626735 TI - Short- and long-term comparative study of anistreplase versus streptokinase in acute myocardial infarction. AB - Streptokinase is well established as an effective thrombolytic. Anistreplase, a new thrombolytic drug, is a complex of streptokinase and acylated human plasminogen that can be administered by intravenous bolus and activates plasminogen at the clot site. Although both streptokinase and anistreplase are effected in treating myocardial infarction (MI), they have different pharmacologic properties. This study was designed to identify short- and long term differences in their clinical effectiveness, safety in use, and survival rates in patients with acute MI. One hundred ten successive patients under seventy years of age admitted within three hours after onset of sustained chest pain suggestive of acute MI were randomized to receive either 30 units of anistreplase intravenously over five minutes or intravenous injection of 750,000 units of streptokinase over thirty to sixty minutes. Reperfusion was achieved in 34 of the 52 (65%) patients treated with anistreplase and in 41 of the 58 (71%) patients treated with streptokinase (p = NS). The two drugs were equally effective in preserving left ventricular ejection fraction, which was found to be significantly better in patients with anterior wall MI who had achieved reperfusion than it was in those who did not (p less than 0.02). One-month, twelve-month, and thirty-six-month survival rates were high (96% to 88%) with no significant difference between the two treatment groups. The authors conclude that the two drugs are equally effective thrombolytic agents but that anistreplase has the advantage that it can be administered as a bolus injection. PMID- 1626736 TI - Ventricular arrhythmias induced by programmed ventricular stimulation after uncomplicated myocardial infarction. AB - The aim of this study was to correlate the occurrence of ventricular dysrhythmias induced by programmed ventricular stimulation and sudden cardiac death (SCD) after a first episode of acute myocardial infarction (AMI). Twenty-seven consecutive male patients aged fifty-four +/- six (forty-seven to seventy) years were studied prospectively. Thirty days after AMI, patients were submitted to coronary arteriography and programmed ventricular stimulation with the S2-S3-S4 protocol. Noninvasive assessments, including Holter monitoring, ECG stress test, and radionuclide ejection fraction, were also repeated six and twelve months after AMI. Ventricular dysrhythmias were induced in all patients. According to such response, patients were divided into three groups: (1) repetitive ventricular response (n = 9); (2) nonsustained ventricular tachycardia (n = 8); and (3) sustained ventricular tachycardia (n = 10). All patients consistently developed complex ventricular dysrhythmias at Holter monitoring and ECG stress test. One patient from group 2 suffered SCD and another presented a syncope. Similarly, in group 3, 2 patients suffered SCD, 1 during a documented episode of recurrent AMI. Except for 1 patient, radionuclide ejection fraction remained unchanged throughout the study in all cases. SCD was also unrelated to the presence and type of dysrhythmias at noninvasive evaluation. Therefore, the type of ventricular dysrhythmia induced by the S2-S3-S4 protocol has no correlation with late SCD in patients with a first AMI and preserved ejection fraction. PMID- 1626737 TI - Efficacy of antihypertensive medication in orthotopic heart transplant recipients and its effect on renal function. AB - The authors looked at 77 patients following orthotopic heart transplant who received a triple immunosuppressive regimen including cyclosporine to see the effect of various antihypertensive medications on mean arterial blood pressure and renal function. There were 62 men and 15 women retrospectively classified into three groups according to the antihypertensive medications they received. Group 1 included 26 patients followed up for 10.7 +/- 2.7 months who received hydralazine therapy. Group 2 included 32 patients followed up for 9.0 +/- 3.4 months who received angiotensin-converting enzyme inhibition therapy. Group 3 included 19 patients followed up for 10.1 +/- 3.3 months who received beta adrenergic blocking agents. Mean arterial pressure (MAP), serum blood urea nitrogen (BUN), and serum creatinine (CR) were determined for each group at the start and end of the follow-up period. The MAP at the start of the study was 107 +/- 14 in group 1, 110 +/- 13 in group 2, and 100 +/- 11 in group 3. It was not statistically significantly different in any of the groups. At the end of the follow-up period, MAP was 112 +/- 10, 111 +/- 10, and 106 +/- 12 for the three groups respectively, and it was not significantly different in any group. The serum BUN in group 3 was 25 +/- 8 mg/dL at the start of the study, and it was not significantly lower than that in group 1, 28 +/- 6, but it was significantly different from that in group 2, 34 +/- 9, P less than 0.05. At the end of the follow-up period, the difference was still maintained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626739 TI - Heterogeneity of rabbit aortic endothelial cells, with special reference to phagocytosis. AB - Heterogeneity of aortic endothelial cells with regard to phagocytotic ability was examined by injecting India ink into normal rabbits. Light and electron microscopic analyses revealed that particles of India ink were phagocytosed in the endothelial cells, which in turn were localized at the distal side of the orifice of aortic branches, especially those of brachiocephalic, left clavicular, and dorsal intercostal arteries. No remarkable differences were found ultrastructurally between phagocytosing and nonphagocytosing endothelial cells. Ingested India ink particles were present within phagosomes of the endothelial cells for several hours after injection; the particles eventually accumulated in the subendothelial space twenty-four hours after injection. These results indicate that an active transport system of large molecules via the phagocytotic processes is present in endothelial cells located at the distal sides of the orifice of aortic branches. These regions are known to develop initial atherosclerotic lesions in hypercholesterolemic animals. Thus, a possible correlation between phagocytotic ability of endothelial cells and development of atherosclerosis is suggested. PMID- 1626738 TI - A four year clinical and echographic follow-up of asymptomatic carotid plaque. AB - Eighty-five patients with asymptomatic carotid plaque--a diagnosis revealed by B mode high-resolution echotomography--were followed up for four years; the echoplaque changes were compared with the clinical history. Eight patients died (2 from stroke, 4 from myocardial infarction, and 2 from lung tumor) and were excluded from the follow-up. Three patients underwent carotid thromboendarterectomy (TEA) (1 bilateral), and these 4 carotids were not considered in the total series. At the first echo Doppler evaluation of 150 carotids, plaques were observed in 112; 38 vessels were free of lesions. Of the 150 carotids, 8 revealed a new plaques. In regard to the echogenic pattern, 95 of the 112 plaques (84.8%) remained unchanged, 16 (14.3%) progressed, and regression of a small homogeneous plaque was observed in 1 patient (0.9%). An increase of the degree of vascular stenosis, was observed in 23 of the 150 carotids (15.3%). Cerebral ischemic symptoms occurred in 5 patients. In 1 patient who suffered from stroke, a new, soft, dyshomogeneous plaque in the carotid of the side of the lesion was observed. In 3 patients (2 with strokes, 1 with transient ischemic attack) the occlusion of a previous severe stenosis was observed. The fifth patient had a stroke on the side of an unchanged, ulcerated hemodynamic lesion. A valid criterion for identifying a risky plaque should be the joint evaluation of the echostructural characteristics and the degree of stenosis. PMID- 1626740 TI - Blood rheology after LDL apheresis using dextran sulfate cellulose absorption--a case report. AB - The authors describe a thirty-eight-year-old woman with familial hypercholesterolemia treated by dextran sulfate cellulose adsorption apheresis. This technique and the selective extracorporeal LDL cholesterol elimination by immunoabsorption or heparin-induced precipitation not only dramatically decrease blood lipids but also result in a marked improvement in the rheologic profile. It is suggested that the amelioration of blood rheology by LDL apheresis may represent the cause for the early clinical improvement felt by most patients with severe coronary heart disease and hypercholesterolemia. PMID- 1626741 TI - Intralobar sequestration of the lung presenting as a continuous murmur--a case report. AB - An eighteen-year-old asymptomatic woman with a continuous murmur, normal two dimensional echocardiogram, and mild haziness of the left lower segment of the lung on chest x-ray was diagnosed to have sequestration based on the presence of a large anomalous systemic artery arising from the descending thoracic aorta supplying the lower lobe of the left lung. Normal bronchial connections with the rest of the lung on bronchoscopy and delayed dye clearance from the left lower lobe bronchioles on bronchogram indicated its intralobar nature. The cause of the continuous murmur was thought to be the large flow through the anomalous systemic artery. PMID- 1626742 TI - Congenital antithrombin III deficiency causing mesenteric venous infarction: a lesson to remember--a case history. AB - Congenital antithrombin III deficiency is an uncommon but important cause of venous thrombosis, usually presenting with recurrent or atypical venous thromboembolism. Its importance lies in the fact that early recognition can lead to treatment in the acute stage, which can prevent propagation of the disease, and further prophylactic treatment may reduce the incidence of further episodes. The authors present a case of mesenteric venous infarction associated with congenital antithrombin III deficiency and briefly discuss the diagnosis, surgical implications, and treatment of this disorder. PMID- 1626743 TI - TIAs in a spontaneously dissecting aneurysm of the internal carotid artery--a case report. AB - A spontaneous internal carotid artery dissection of an aneurysmal form is reported. The patient, a fifty-eight-year-old man, had manifested recurrent transient left hemiparesis, dysesthesia of the left upper limb, and dysarthria for three months. After administration of ticlopidine, the transient ischemic attacks completely disappeared. Three months later, the follow-up angiographic study revealed the same form of dissection in the same portion as compared with the initial study. Conservative therapy was successful. PMID- 1626744 TI - Mandibular incisor extraction--postretention evaluation of stability and relapse. AB - Pretreatment, posttreatment and 10-year postretention dental cast and lateral cephalogram records of 42 patients were evaluated. Each patient had undergone edgewise orthodontic treatment following removal of one or two mandibular incisors and various maxillary teeth. Seven of 24 patients (29%) in the single incisor extraction group and 10 of 18 (56%) patients in the two-incisor extraction group demonstrated unacceptable mandibular incisor alignment at the postretention stage. This result was considerably more favorable than the results of previously reported premolar extraction cases (70% unacceptable alignment at postretention). Intercanine width decreased during treatment and continued to decrease postretention in most cases. Overbite and overjet remained acceptable. No associations could be found to predict the amount of relapse. PMID- 1626745 TI - Periodontal considerations in the use of bonds or bands on molars in adolescents and adults. AB - This longitudinal study compared the periodontal status of bonded and banded molars in 20 adult and 40 adolescent patients before, during and after treatment with fixed orthodontic appliances. Plaque accumulation (measured by the Plaque Index), gingival inflammation (measured by the Gingival Index and the bleeding tendency), and pocket depth were assessed by one examiner at sites along the mesio-buccal line angle of the maxillary right first molar and the mandibular left first molar. Assessments were made immediately prior to the placement of fixed appliances (pretreatment), at 1, 3, 6, 9, 12 and 18 months after appliances were placed; and 3 months after appliances were removed (posttreatment). Loss of attachment between the pretreatment and posttreatment visits also was determined. At pretreatment, no significant differences were found in gingival inflammation between maxillary and mandibular banded and bonded molars. During treatment, both maxillary and mandibular banded molars showed significantly (p less than 0.05) greater gingival inflammation and plaque accumulation than did bonded molars. Three months after appliance removal, the maxillary molars that had been banded continued to show significantly more gingival inflammation and loss of attachment than did the maxillary molars that had been bonded. When all banded and bonded teeth were grouped by patient age, mean values for plaque accumulation and gingival inflammation in the maxillary molar regions were significantly greater for adolescents than for adults. PMID- 1626746 TI - A proportional analysis of the soft tissue facial profile in young adults with normal occlusion. AB - A proportional soft tissue profile analysis is presented, based on natural head position (NHP) and an extracranial vertical reference line through Porion. Twelve linear soft tissue variables and norms for 11 indices expressing vertical and horizontal soft tissue proportions of the face were obtained from lateral skull radiographs of 40 Swedish adults (20 males, and 20 females) with good occlusion. Sexual dimorphism, with larger dimensions in men than in women, was most pronounced in the vertical plane. With regard to facial soft tissue proportions, significant differences between men and women were found only for those indices which involved measurements of lower jaw prominence and facial height. The means and standard deviations for six indices in the female group were compared with corresponding data obtained from the Peck and Peck sample, which had been selected on esthetic grounds. The results showed a close match between the groups. The proportional soft tissue analysis is recommended for the treatment planning of patients scheduled for orthognathic surgery. PMID- 1626747 TI - A comparison of the effects of first premolar extractions on third molar angulation. AB - The effect of third molars on the stability of orthodontic treatment has been studied extensively. Yet the effect of orthodontic treatment, particularly premolar extractions, on third molars has not been substantially studied. The purpose of this investigation was to compare the changes in third molar angulation in patients treated with and without extractions. Records of 45 Class I, nonextraction and 33 Class I, first premolar extraction patients were examined. The pretreatment and posttreatment pantographs were digitized, and the angles between the third molar long axes and the occlusal plane were measured. Changes in third molar angulation from pretreatment to posttreatment for the two groups were compared for statistical differences using a Student's t-test. Statistical analysis revealed there were no significant differences in the change in third molar angulation in either group. On average, the maxillary and mandibular third molars showed an improvement in angulation relative to the occlusal plane. The results suggest that factors other than first premolar extractions may influence third molar angulation. PMID- 1626748 TI - Craniofacial pattern of Class III deciduous dentition. AB - The purpose of this study was to investigate the morphological characteristics of the cranio-dento-facial complex of children with deciduous dentition and Class III malocclusion. Forty Chinese children in Taiwan with normal occlusion and 40 with Class III malocclusion in deciduous dentition were selected for cephalometric analysis. Mandibular length was significantly greater and the mandible was situated farther forward in the Class III group. The maxilla was also slightly backward in this group, perhaps in association with the shorter maxillary length. The mandibular incisors were tipped lingually to compensate for the intermaxillary skeletal dysplasia and the maxillary incisors were tipped lingually by the retroinclined mandibular incisors. PMID- 1626749 TI - Problems associated with ceramic brackets suggest limiting use to selected teeth. AB - Ceramic brackets became popular as esthetic appliances which could withstand orthodontic forces and resist staining better than plastic brackets. Several clinical complications may arise from the use of ceramic brackets. They include the effects debonding can have on underlying enamel, attrition of teeth occluding with ceramic brackets and increased friction in the orthodontic appliance. Solutions to these problems are discussed which indicate the need for careful selection of teeth to be bonded with ceramic brackets. PMID- 1626750 TI - Case report HL. PMID- 1626751 TI - The orthodontist's role in managing traumatic dental injuries. PMID- 1626752 TI - Vertical malocclusion article raises questions. PMID- 1626753 TI - Vertical malocclusion article raises questions. PMID- 1626754 TI - The gingival smile line. AB - A comparative study was performed to examine the nature of the gingival smile line (GSL), a specific dentolabial configuration characterized by the exposure of maxillary anterior gingiva during a full smile. Five soft-tissue, three dental and three skeletal variables were selected, measured and reported for a GSL sample (n = 27) and a reference sample (n = 88), both consisting of North American white orthodontic patients with a median age of 14.4 years. The results indicated that the capacity to project a gingival smile was related to: anterior vertical maxillary excess and the muscular ability to raise the upper lip significantly higher than average when smiling. Other variables significantly associated with GSL were greater overjet, greater interlabial gap at rest, and greater overbite. Factors that did not appear associated with the GSL phenomenon were upper-lip length, incisor clinical crown height, mandibular plane angle, and palatal plane angle. Clinical aspects of GSL were discussed. PMID- 1626755 TI - Intranasal administration of a beta adrenergic amine: an alternative to metered dose inhalers. AB - In anesthetized, artificially ventilated guinea pigs, intranasal and intravenous administration of albuterol produced the same maximum degree of protection against bronchoconstriction induced by bilateral electrical stimulation of the cervical vagal nerves. Intranasal albuterol showed a slower onset of action than intravenous albuterol and exhibited equivalent cardiovascular side effects for the same level of bronchoprotection. Accordingly, intranasal albuterol may represent an alternative to metered-dose inhalation for prophylaxis and treatment of bronchoconstriction in humans. PMID- 1626756 TI - Delayed hypersensitivity to diltiazem in two patients. AB - We report two cases of cutaneous adverse reactions during treatment with diltiazem. Both patients developed wide-spread, pruriginous, erythematous, maculopapular eruptions with fever and facial angioedema, 48 to 72 hours after starting diltiazem. Delayed hypersensitivity to diltiazem was suspected and the diagnosis was confirmed by skin patch tests followed by cutaneous biopsy. PMID- 1626757 TI - Comparison of terbutaline Turbuhaler and albuterol chlorofluorocarbon (CFC) inhaler in middle-aged and elderly patients with obstructive lung disease. AB - The aim of the present study was to compare the effect of terbutaline Turbuhaler (0.5 mg qid) with that of albuterol chlorofluorocarbon (CFC) inhaler (0.2 mg qid) in middle-aged and elderly patients with obstructive lung disease. The study was performed as an open cross-over (2 x 2 weeks) and randomized study in 85 patients. A significant increase in PEF was seen after inhalation from both devices (P less than .001). Baseline PEF values before inhalation were higher with Turbuhaler than with the CFC inhaler both in the mornings and in the evenings. Fifty-six percent of the patients preferred terbutaline Turbuhaler and 26% albuterol CFC inhaler (P = .004). PMID- 1626758 TI - Malignant idiopathic anaphylaxis: three additional cases and extended evaluation. AB - Northwestern University's Division of Allergy and Immunology (NUAI) has evaluated and treated 225 patients with idiopathic anaphylaxis (IA) over a period of 16 years. Four patients have been identified with malignant IA. The term "malignant" is used to identify those patients with the most severe form of IA that is resistant to standard therapy. The diagnosis of malignant IA is made in patients with IA whose controlling oral corticosteroid dose was not able to be reduced below 60 mg of prednisone (or its equivalent) every other day or 20 mg of prednisone (or its equivalent) every day without an exacerbation of IA. Presented here is the long-term evaluation of one patient as well as three additional patients with malignant IA managed by our service. At the time of this report we have had no deaths due to IA in patients treated with pharmacologic regimen. PMID- 1626759 TI - Isolated early response after nasal allergen challenge is sufficient to induce nasal hyperreactivity. AB - Ten rhinitic patients allergic to grass pollen were challenged with histamine intranasally 24 hours before and 24 hours after nasal provocation with grass pollen. Up to ten hours after allergen provocation nasal lavage fluid was obtained to characterize early and late phase reactions by measuring the levels of histamine and leukotrienes as indicators of mediator release, and albumin as a marker of increased vasopermeability. Ten minutes after allergen challenge with 10,000 BU grass pollen extract LTC4,D4, and albumin significantly increased from 62 to 576 pg/mL (P = .008) and from 15 to 81 micrograms/mL (P = .008), respectively, without significant changes after placebo challenge a week earlier. Although the patients showed increased responsiveness to histamine after allergen challenge compared with a placebo-challenged control group (P = .02), one patient only demonstrated a late phase nasal allergic reaction characterized by recurrence of clinical symptoms eight to ten hours after allergen challenge and recurrence of mediators in lavage fluid. It is concluded that an isolated early response after allergen challenge is sufficient to induce nasal hyperreactivity. A biochemically or clinically defined late phase allergic reaction does not necessarily accompany allergen-induced hyperreactivity. PMID- 1626760 TI - Immunoassay of specific IgE: use of a single point calibration curve in the modified radioallergosorbent test. AB - Interest in immunoassay standardization has prompted development of specific IgE assays reporting results related to the international IgE reference. To examine the single point calibration curve employed in the modified RAST assay (MRT) to convert MRT counts to IgE units, independent dilutions of a 25 kU/L total IgE reference and nine allergic sera (three each for short ragweed, cat, and timothy) were made in horse serum and assayed. In a log-log plot, the single point curve was, by definition, linear over its entire range; the dilution curve was curvilinear because of reagent system saturation, which was at 7 kU/L. Curves were not parallel (P less than .001). Allergen-specific dilution curves showed saturation points at values similar to or less than the total IgE system. The linear portions of these curves paralleled the total IgE dilution curve but not the single point curve. This lack of parallelism would have resulted in varying magnitudes of error in estimation of IgE antibody levels in the upper and lower assay ranges, and would imply a lower detection limit for IgE than that which the assay actually has. Modified RAST assay is not appropriate in research or a clinical situation in which accurate quantitative results are needed. Modified RAST assay would furthermore be an inappropriate means of assigning units to proposed reference preparations for standardization. PMID- 1626761 TI - Etiologic factors in childhood chronic urticaria. AB - In order to identify the etiologic factors in childhood chronic urticaria, we studied 226 children, 122 boys and 104 girls, aged 1 to 14 (mean = 8.14) years with chronic urticaria and/or angioedema. The initial evaluation consisted of a thorough history, physical examination, and basic laboratory tests. Specific in vivo and in vitro tests were done according to the findings of the initial evaluation. Urticaria alone was present in 78.4% of the patients, angioedema alone in 6.6%, and both urticaria and angioedema in 15% of the patients. Chronic urticaria was attributed to physical factors in 6.2% of the patients, infections in 4.4%, aeroallergens in 2.2%, foods in 4%, food additives in 2.6%, and drugs in 1.8% of the patients. Overall, causal factors of chronic urticaria were found in 21.2% of the patients. PMID- 1626762 TI - High prevalence of celiac disease in healthy adults revealed by antigliadin antibodies. AB - Sera from 1866 healthy blood donors and from 40 untreated adults with celiac disease were analyzed using a micro-ELISA assay. Blood donors with IgA antigliadin activity greater than 40 units corresponding to the 96.8th percentile and IgG antigliadin activity greater than 20 units corresponding to the 91.3rd percentile were selected for further investigation and jejunal biopsy. Seven of 49 blood donors with high IgA antigliadin activity showed mucosal lesions typical for celiac disease. None of the donors with high IgG antigliadin activity (35 subjects) but without high IgA activity had such mucosal lesions. A prevalence of celiac disease of at least 1/256 was observed in the donor group. There were significant age-group differences in IgA antigliadin activity. In the present study, a high IgA antigliadin activity had a positive predictive value between 18% and 25% in individuals without symptoms indicative of celiac disease depending on the way the cut-off points were chosen. In contrast, the positive predictive value of high IgG antigliadin activity alone was estimated to be 0%. PMID- 1626764 TI - Improving compliance. PMID- 1626763 TI - Continuous nebulization for status asthmaticus. AB - Continuous nebulization of beta 2 agonists is now recognized as a useful treatment for severe exacerbations of asthma. This mode of administration has been described both for adults and children in the emergency room and in the intensive care unit. It has been suggested that early use of continuous inhalation therapy may reduce or prevent the need for intensive care unit admissions and potentially toxic treatments such as intravenous beta agonists and mechanical ventilation. A number of methods have been proposed for continuous administration of beta agonists, however, there is no concensus as to the best one. The lack of controlled studies clearly demonstrating superior outcomes in patients who receive this treatment leaves many questions unanswered. In addition, differences in efficacy and safety between frequent and continuous nebulization, if any, are unclear. Adverse effects primarily consist of muscle cramps, hypokalemia, and hyperglycemia. It is suggested that use of this treatment should be considered for the asthmatic patient who demonstrates progression towards significant obstruction before institution of the more toxic treatments listed above. While continuous nebulization has not been proven to prevent the need for them, it is clearly safer. Should population studies eventually fail to demonstrate its superior efficacy, continuously nebulized beta 2 agonist therapy may still be beneficial for individual patients. PMID- 1626765 TI - Pharmacist substitution of slow-release products. PMID- 1626766 TI - Monitoring for airborne allergens. AB - Monitoring for allergens can provide some information on the kinds and levels of exposure experienced by local patient populations, providing volumetric methods are used for sample collection and analysis is accurate and consistent. Such data can also be used to develop standards for the specific environment and to begin to develop predictive models. Comparing outdoor allergen aerosols between different monitoring sites requires identical collection and analysis methods and some kind of rational standard, whether arbitrary, or based on recognized health effects. PMID- 1626767 TI - Microvascular circulation of the descending colon in horses. AB - The microvascular circulation of the descending colon was studied in 5 adult horses, using microangiography and light microscopy combined with gross studies and scanning electron microscopy of vascular replicas. After heparinization, horses were euthanatized, and 3 segments of the descending colon and its mesentery containing 1 vascular arcade were removed from each horse. The fecal balls were gently massaged from the lumen, and the blood was flushed free of the circulation with isotonic NaCl. In 5 segments, the vascular system was injected with a modified radiopaque medium and evaluated radiographically. Specimens examined radiographically also were prepared for histologic examination, using standard methods. Ten segments were injected with 1 of 2 types of plastics and studied grossly or by scanning electron microscopy. Arcuate arteries gave rise to a descending colonic rete that surrounded the vein and supplied numerous descending colonic lymph nodes. The rete also supplied the mesocolon and the descending colonic tissue. Short filamentous vessels arising from the rete directly penetrated the mesenteric tenia to supply an intermuscular plexus between the longitudinal and circular muscle layers of the muscularis externa. Larger vessels arising from either side of the rete divided into the long- and short-terminal arteries that supplied an extensive submucosal plexus, which was continuous around the circumference. The submucosal plexus supplied the mucosa, the tunica muscularis, and the serosa. Vessels running centrifugally from the submucosal plexus formed an intermuscular plexus between the longitudinal and circular muscle layers of the muscularis externa. The intermuscular plexus at the mesenteric angle also was supplied by vessels branching from the short-terminal arteries as they penetrated the muscularis externa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626768 TI - Anatomic and radiographic study of the lacrimal apparatus of llamas. AB - The anatomy of the nasolacrimal duct of llamas was examined grossly and radiographically in 2 llamas. Dacryocystorhinography was performed on cadaver heads, using a radiographic aqueous contrast agent. Anatomic casts of the nasolacrimal apparatus were obtained by cannulation of the duct and use of polyurethane cast material. Dacryocystorhinography accurately revealed the nasolacrimal apparatus and compared favorably with gross dissections and polyurethane casts. PMID- 1626769 TI - Effects of two adenoviruses (type 1 and type 8) on functional properties of bovine alveolar macrophages in vitro. AB - Cultures of bovine alveolar macrophages were inoculated with type-1 and type-8 adenoviruses, initially isolated from calves with respiratory tract disease, and functional properties of the cells were observed over a period of 10 to 11 days. Both viruses replicated in macrophages; viral titers were low (less than 3.75 log10 TCID50/0.1 ml), and intranuclear inclusions were detected by indirect immunofluorescence in 5 to 10% of the cells from 3 days after inoculation. Highest titers were induced by type-1 adenovirus, which also induced the greatest functional changes. Expression of Fc and complement receptors was reduced by both viruses, although the greatest effects were seen with type 1. Phagocytosis of Candida krusei cells was reduced following type 1 infection, whereas phagocytosis in type-8-infected cells was not different from that of noninfected macrophages. Ability to kill ingested Candida cells also was reduced following type-1 infection, whereas type-8-infected macrophages had lower killing ability only at 2 to 4 days after inoculation. Neither virus had substantial effects on the production of neutrophil chemotactic factors by the macrophages. PMID- 1626770 TI - Investigation of antibodies to extractable nuclear antigens in dogs. AB - Determination of antibodies to specific nuclear antigens, termed extractable nuclear antigen (ENA), was investigated in healthy dogs and in dogs with autoimmune, inflammatory, and neoplastic diseases. Using a counterimmunoelectrophoresis method, the dogs' sera were tested for antibodies against the nuclear antigens single-stranded DNA, Sm, Ro, La, ribonucleoprotein, Scl, and proliferating cell nuclear antigen. Antibodies to the Ro antigen were found in 1 dog with discoid lupus erythematosus, in 1 dog with pemphigus erythematosus, and in 1 dog with facial pyoderma and chronic superficial keratitis. In 15 dogs, antibodies were detected to ENA, but the precipitin lines were too weak to identify the specific ENA. These antibodies were found in some dogs with systemic lupus erythematosus, discoid lupus erythematosus, pemphigus erythematosus, dermatomyositis, vitiligo, lymphoma; in the dog with facial pyoderma and chronic superficial keratitis; and in 1 healthy dog. The highest percentage of dogs with antibodies to ENA in a large series (greater than 8) of this study was in dogs with systemic lupus erythematosus (4 of 13; 31%). PMID- 1626771 TI - Cardiopulmonary, anesthetic, and postanesthetic effects of intravenous infusions of propofol in greyhounds and non-greyhounds. AB - The cardiopulmonary, anesthetic, and postanesthetic effects of an IV infusion of the hypnotic agent propofol were assessed in 6 Greyhounds and 7 non-Greyhounds. After IM injection of acetylpromazine and atropine, a bolus injection of propofol sufficient to allow endotracheal intubation (mean +/- SEM = 4.0 +/- 0.3 mg/kg of body weight in Greyhounds; 3.2 +/- 0.1 mg/kg in non-Greyhounds) was administered, followed by continuous infusion at a rate of 0.4 mg/kg/min for 60 minutes, during which time dogs breathed 100% oxygen. In 23% of all dogs (3 of 13), apnea developed after initial bolus administration of propofol. Arterial blood pressure was well maintained in all dogs, but heart and respiratory rates were decreased significantly (P less than 0.05) during the infusion in Greyhounds. In Greyhounds, mild respiratory acidosis developed after 45 minutes, whereas arterial carbon dioxide tension was increased at all times after propofol administration in non-Greyhounds. In all dogs, PCV and total plasma proteins were unaffected by propofol. Rectal temperature decreased during treatment. Muscle tremors were observed in approximately 50% of dogs (in 3 of 6 Greyhounds and 3 of 7 non-Greyhounds) during and after infusion of propofol. Non-Greyhounds lifted their heads, assumed sternal recumbency, and stood 10 +/- 1, 15 +/- 3, and 28 +/- 5 minutes, respectively, after the end of the infusion; in Greyhounds, the corresponding times were 36 +/- 4, 43 +/- 6, and 63 +/- 7 minutes. PMID- 1626772 TI - Hematologic and serum biochemical effects of long-term administration of anti inflammatory doses of prednisone in dogs. AB - Results of routine hematologic and serum biochemical analyses from 12 healthy adult male dogs that were given prednisone (0.55 mg/kg of body weight, PO, q 12 h) for 35 days were compared with those of a control group of 6 dogs that were given gelatin capsules. Analyses were performed at 2-week intervals during and after prednisone administration. Lymphocyte and eosinophil counts were significantly (P less than 0.005) decreased after 2 and 4 weeks of prednisone treatment, compared with controls. Two weeks after treatment, eosinophil counts in prednisone-treated dogs were similar to those of control dogs, whereas lymphocyte counts remained low 4 weeks after treatment in treated dogs (1,869 +/- 145 cells/microliters), compared with that in control dogs (3,662 +/- 548 cells/microliters). Neutrophil and monocyte counts did not significantly change during glucocorticoid administration. Mean platelet volume significantly (P less than 0.001) decreased after 4 weeks of prednisone treatment, but returned to pretreatment values by 2 weeks after treatment. Four weeks of prednisone treatment did not cause significant increased activity in serum alanine transaminase, total alkaline phosphatase or the steroid-induced isoenzyme of alkaline phosphatase. Significant increases in serum albumin (P less than 0.001) and total protein (P less than 0.05) concentrations were detected after 4 weeks of treatment, but mean values were not significantly different from those of controls 2 weeks after treatment ended. Results of our study indicate that eosinophil and lymphocyte counts are the most sensitive indicators of long-term glucocorticoid administration at anti-inflammatory dosages of 1.1 mg/kg daily. PMID- 1626773 TI - Morphologic and biochemical study of sternal cartilage autografts for resurfacing induced osteochondral defects in horses. AB - Using biodegradable pins, sternal cartilage autografts were fixed into osteochondral defects of the distal radial carpal bone in ten 2 to 3-year-old horses. The defects measured 1 cm2 at the surface and were 4 mm deep. Control osteochondral defects of contralateral carpi were not grafted. After confinement for 7 weeks, horses were walked 1 hour daily on a walker for an additional 9 weeks. Horses were euthanatized at 16 weeks. Half of the repair tissue was processed for histologic and histochemical (H&E and safranin-O fast green) examinations. The other half was used for the following biochemical analyses: type-I and type-II collagen contents, total glycosaminoglycan content, and galactosamine-to-glucosamine ratio. On histologic examination, the repair tissue in the grafted defects consisted of hyaline-like cartilage. Repair tissue in the nongrafted defects consisted of fibrocartilaginous tissue, with fibrous tissue in surface layers. On biochemical analysis, repair tissue of grafted defects was composed predominantly of type-II collagen; repair tissue of non-grafted defects was composed of type-I collagen. Total glycosaminoglycan content of repair tissue of grafted defects was similar to that of normal articular cartilage. Total glycosaminoglycan content of nongrafted defects was 62% of that of normal articular cartilage (P less than 0.05). Repair tissue of all defects was characterized by galactosamine-to-glucosamine ratio significantly (P less than 0.05) higher than that of normal articular cartilage. These results at 16 weeks after grafting indicate that sternal cartilage may potentially constitute a suitable substitute for articular cartilage in large osteochondral defects of horses. PMID- 1626774 TI - Lymphoscintigraphy in healthy dogs and dogs with experimentally created thoracic duct abnormalities. AB - Lymphoscintigraphic evaluation of the thoracic duct (TD) was performed in 10 healthy and 12 dogs with experimentally created TD abnormalities (6 dogs with TD lacerations and 6 dogs with cranial vena ligations). Complete imaging took 4 hours and caused no adverse effects or complications. Lymphoscintigraphy of healthy dogs failed to image the TD; however, background activity in the abdomen and thorax, and radioactivity in the kidneys, bladder, liver, and heart were noticed. Lacerations and transections of the TD were experimentally created in 6 dogs to ascertain whether TD rupture could be detected with lymphoscintigraphy. Lymphoscintigraphy was performed within 48 hours of creating the TD defect. There was no significant difference in the scintigraphic pattern of healthy dogs and those with experimentally created TD defects. Ligation of the cranial vena cava was performed in 6 dogs; 3 dogs developed chylothorax. In those 3 dogs, diffuse radioactivity was imaged in the thorax and was compatible with thoracic lymphangiectasia. In one of these dogs, linear activity consistent with the TD and localized regions of radioactivity cranial to the heart (compatible with the mediastinal lymph nodes) were noticed. Lymphoscintigraphic findings in these dogs correlated with lymphangiographic findings. PMID- 1626775 TI - Evaluation of sulbactam plus ampicillin for treatment of experimentally induced Klebsiella pneumoniae lung infection in foals. AB - Efficacy of sulbactam, a beta-lactamase inhibitor, in combination with ampicillin, was evaluated for treatment of experimentally induced pneumonia caused by beta-lactam-resistant Klebsiella pneumoniae. Infection was experimentally induced in 18 healthy weanling foals that were randomly allocated to 3 treatment groups: sulbactam plus ampicillin (S/A, 3.3 and 6.6 mg/kg of body weight, respectively), ampicillin (6.6 mg/kg), or vehicle only. Foals were treated daily for 7 days; the observer was unaware of treatment status. Compared with ampicillin and vehicle, treatment with S/A resulted in a statistically significant (P less than 0.05) decrease in severity of pneumonia, with regard to bronchoalveolar lavage cytologic findings (decreased total cell and neutrophil numbers, and increased lymphocyte numbers) and extent of macroscopic lesions in lung tissue of the noninoculated regions. Marked trends toward improvement of S/A treated foals were observed for quantitative results of bacteriologic culture of bronchoalveolar lavage fluid samples (P less than 0.07), macroscopic pathologic features of the whole lung (P less than 0.1), and histopathologic variables (P less than 0.07), compared with ampicillin- and vehicle-treated foals. Treatment effects were not observed for radiographic, hematologic, and blood gas abnormalities that resulted from infection. In conclusion, the combination of sulbactam plus ampicillin was found to have synergistic effects in vivo, to reduce the extent and severity of experimentally induced gram-negative lung infection in foals. PMID- 1626776 TI - In vitro comparison of equine granulocytes labeled with 99mTc hexamethylpropyleneamine oxime or 111In-oxine. AB - Isolated equine granulocytes (WBC), radiolabeled with 99mTc hexamethylpropyleneamine oxime (99mTc-HMPAO) or 111In-oxine, were evaluated in vitro for their labeling characteristics, viability, and phagocytic function over a 6-hour postlabeling period. Mean +/- SD labeling efficiency for 111In-oxine-WBC was 62.2 +/- 15.3%, which was significantly (P less than 0.001) higher than that for 99mTc-HMPAO-WBC (32.0 +/- 17.0%). In vitro elution of radiolabel from cells was significantly (P less than 0.02) greater for 99mTc-HMPAO-WBC at 0.5, 2, and 4 hours, but was not significantly different from elution of radiolabel for 111In oxine-WBC at 6 hours. Viability, assessed by trypan blue dye exclusion, for 99mTc HMPAO-WBC, 111In-oxine-WBC, and nonlabeled control WBC ranged from 97 to 100%, and was not significantly different among groups. Cell function was assessed by use of a phagocytosis assay and was reported as phagocytic index. The phagocytic index ranged from 0.86 to 0.96 for 99mTc-HMPAO-WBC, and from 0.76 to 0.97 for 111In-oxine-WBC. The phagocytic index was not significantly different at 0.5, 2, or 4 hours, but was significantly (P = 0.038) greater at 6 hours for 99mTc-HMPAO WBC. Because of the superior imaging characteristics of 99mTc-HMPAO-WBC and equal or better labeling characteristics than those for 111In-oxine at 6 hours, 99mTc HMPAO-WBC appear to be a good alternative to 111In-oxine-WBC. PMID- 1626777 TI - Evaluation of an enzyme-linked immunosorbent assay for diagnosis of trichinellosis in swine. AB - Experimental and field trials were conducted to evaluate an ELISA for its ability to detect Trichinella-infected domestic swine and to compare ELISA results with muscle-digestion test results. The ELISA used was a commercial double-antibody kit, containing an excretory-secretory antigen, and was evaluated principally for epidemiologic use. Experimentally induced infection in swine (4 groups of 3 pigs each; inoculated with 0, 50, 500 or 5,000 larvae) was detected as early as postinoculation week 4, with seroconversion of all inoculated swine by postinoculation week 8. The rate of seroconversion appeared to be affected by initial larval dose, time after inoculation, and immunocompetence of the individual host. Determination of antibody kinetics generally revealed rapidly increasing antibody titer, followed by its steady decrease in most pigs. Once seropositive, however, all pigs remained seropositive for the duration of the 10 week study. Presence of muscle larvae was confirmed in all infected pigs at termination of the study. We recognize that the experimental conditions may not be truly representative of those under which natural infection develops in pigs; however, the ELISA detected an infected pig with muscle larval density of 0.87 larvae/g of tissue. Results of a field trial (n = 310) indicated no muscle digestion test-positive pigs (35 g of diaphragm muscle digested/pig), but 3 samples tested positive by ELISA for specificity of 99.0%. PMID- 1626778 TI - Effects of intracameral injection of tissue plasminogen activator on corneal endothelium and intraocular pressure in dogs. AB - Contact wide-field specular microscopy was performed on eyes of 16 healthy dogs after tissue plasminogen activator at a concentration of 25 micrograms/100 microliters (group 1, n = 8) or 50 micrograms/100 microliters (group 2, n = 8) was injected into 1 anterior chamber of each dog. The contralateral eye served as a nontreated control. Applanation tonometry was used to measure intraocular pressure in both eyes for up to 168 hours. By use of computerized morphometric analysis and pachymetry, changes from baseline values in endothelial cell density, cell morphologic features, and corneal thickness were evaluated at postinjection hours 24, 48, and 168. Significant mean differences in intraocular pressure were not detected between treated eyes of group-1 dogs and those in group 2 at designated times, or between treated and nontreated eyes of dogs in either group. Mean corneal thickness of treated and nontreated eyes was similar in both groups through postinjection hour 168. Changes in mean percentage of endothelial cell sides were observed only in treated eyes of group-2 dogs, with the mean percentage of hexagons at postinjection hour 168 decreasing by 18%, a decrease that was significantly (P less than 0.05) greater than the decrease in nontreated eyes. The mean percentage of 6-sided cells in treated eyes of group-2 dogs was significantly (P less than 0.05) less than that in treated eyes of group 1 dogs at postinjection hour 168. PMID- 1626779 TI - Use of tissue plasminogen activator for intraocular fibrinolysis in dogs. AB - Fibrin clots were induced in eyes of dogs by injection of autogenous citrated plasma into the anterior chamber. Twenty-four hours after clot formation, 0.01 ml of tissue plasminogen activator at a concentration of 1 microgram/100 microliters (group 1, n = 5) or 25 micrograms/100 microliters (group 2, n = 5) was injected into 1 anterior chamber of each dog. The contralateral eye served as a nontreated control. Serial photographs were taken of the fibrin clots after intracameral injection of tissue plasminogen activator. Computerized morphometric analysis was then used to evaluate changes in cross-sectional surface area of the fibrin clot. Significant (P less than 0.001) fibrin-clot lysis was detected in treated eyes of group-2 dogs, but was not found in treated eyes of group-1 dogs. A mean decrease of greater than 90% in clot surface area was detected by 120 minutes after injection in treated eyes of group-2 dogs. PMID- 1626780 TI - Detection of hemorrhagic septicemia virus of salmonid fishes by use of an enzyme linked immunosorbent assay containing high sodium chloride concentration and two noncompetitive monoclonal antibodies against early viral nucleoproteins. AB - Inclusion of high-ionic strength buffers helped us to develop a sandwich ELISA to detect hemorrhagic septicemia virus (HSV) in cell culture and infected trout tissue extracts. For maximal sensitivity of 0.1 to 0.2 ng/well/100 microliters or about 10 to 50 TCID50/well/100 microliters, trout extracts were diluted 1:1 and assayed for the earliest synthesized nucleoprotein N. Simultaneous binding of the N protein from HSV in the sample to the wells coated with monoclonal antibody (2D5 against the N protein) and to the peroxidase-labeled monoclonal antibody (2C9 against the N protein) proceeded during a 2-hour incubation at 20 to 22 C (room temperature). The response was linear between 6 to 60 ng/well of purified virus. Monoclonal antibodies used were noncompetitive with each other and reacted with F1, F2, 23.75, and 5 Spanish isolates of HSV, but not with infectious hematopoietic necrosis or infectious pancreatic necrosis viruses. Tissue specimens with low content of HSV virus may now be assayed directly without use of cell culture, rapidly, and with high precision, during the acute phase of the disease in salmonid fishes. PMID- 1626781 TI - Effects of xylazine on ventilation in horses. AB - The effects of 3 commonly used dosages (0.3, 0.5, and 1.1 mg/kg of body weight, IV) of xylazine on ventilatory function were evaluated in 6 Thoroughbred geldings. Altered respiratory patterns developed with all doses of xylazine, and horses had apneic periods lasting 7 to 70 seconds at the 1.1 mg/kg dosage. Respiratory rate, minute volume, and partial pressure of oxygen in arterial blood (PaO2) decreased significantly (P less than 0.001) with time after administration of xylazine, but significant differences were not detected among dosages. After an initial insignificant decrease at 1 minute after injection, tidal volume progressively increased and at 5 minutes after injection, tidal volume was significantly (P less than 0.01) greater than values obtained before injection. Partial pressure of carbon dioxide in arterial blood (PaCO2) was insignificantly increased. After administration of xylazine at a dosage of 1.1 mg/kg, the mean maximal decrease in PaO2 was 28.2 +/- 8.7 mm of Hg and 22.2 +/- 4.9 mm of Hg, measured with and without a respiratory mask, respectively. Similarly, the mean maximal increase in PaCO2 was 4.5 +/- 2.3 mm of Hg and 4.2 +/- 2.4 mm of Hg, measured with and without the respiratory mask, respectively. Significant interaction between use of mask and time was not detected, although the changes in PaO2 were slightly attenuated when horses were not masked. The temporal effects of xylazine on ventilatory function in horses should be considered in selecting a sedative when ventilation is inadequate or when pulmonary function testing is to be performed. PMID- 1626782 TI - Bronchial circulation during prolonged exercise in ponies. AB - Tracheal, bronchial, and renal flow were studied in 8 healthy ponies at rest and during exercise performed on a treadmill at a speed setting of 20.8 km/h and 7% grade (incline) for 30 minutes. Blood flow was determined with 15-microns diameter radionuclide-labeled microspheres that were injected into the left ventricle when the ponies were at rest, and at 5, 15, and 26 minutes of exertion. Heart rate and mean aortic pressure increased from resting values (40 +/- 2 beats/min and 124 +/- 3 mm of Hg, respectively) to 152 +/- 8 beats/min and 133 +/ 4 mm of Hg at 5 minutes of exercise, to 169 +/- 6 beats/min and 143 +/- 5 mm of Hg at 15 minutes of exercise, and to 186 +/- 8 beats/min, and 150 +/- 5 mm of Hg at 26 minutes of exercise. Tracheal blood flow at rest and during exercise remained significantly (P less than 0.05) less than bronchial blood flow. Tracheal blood flow increased only slightly with exercise. Vasodilation caused bronchial blood flow to increase throughout exercise. Pulmonary arterial blood temperature of ponies also increased significantly (P less than 0.05) with exercise and a significant (P less than 0.005) correlation was found between bronchial blood flow and pulmonary arterial blood temperature during exertion. At 5 minutes of exercise, renal blood flow was unchanged from the resting value; however, renal vasoconstriction was observed at 15 and 26 minutes of exercise. We concluded that bronchial circulation of ponies increased with exercise in close association with a rise in pulmonary arterial blood temperature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626783 TI - Synchronization of estrus in dairy goats treated with prostaglandin F at various stages of the estrous cycle. AB - Dairy goats were given IM injections of 125 micrograms of cloprostenol sodium on day 6 of the estrous cycle (prostaglandin F [PGF] 6, n = 22) or day 12 of the estrous cycle (PGF 12, n = 26). Mean +/- SE hours from injection to onset of behavioral estrus and proportion of goats responding were 46 +/- 4.2 (range, 12 to 88 hours) and 95% and 48 +/- 2.9 (range, 34 to 68 hours) and 100% for groups PGF 6 and PGF 12, respectively. There was no significant difference between the groups in mean time to onset of estrus, but variances about the means were different. Of the does in groups PGF 6 and PGF 12, 67 and 85%, respectively, had signs of onset of estrus between 36 and 60 hours after administration of PGF. Mean (+/- SE) hours from injection to time of peak concentrations of luteinizing hormone (LH) were 62 +/- 3.1 and 64 +/- 2.1 for groups PGF 6 and PGF 12, respectively. Of the does in groups PGF 6 and PGF 12, 86 and 100%, respectively, had LH peaks. Of the does in groups PGF 6 and PGF 12, 68 and 77%, respectively, had peak concentrations of LH between 48 and 72 hours after administration of PGF. All does in groups PGF 6 and PGF 12 had concentrations of progesterone greater than or equal to 1.0 ng/ml on the day of administration of PGF. Concentrations decreased to less than 1.0 ng/ml by 48 hours after injection in all does except 1 in group PGF 6.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626784 TI - Cardiopulmonary responses to experimentally induced gastric dilatation in isoflurane-anesthetized dogs. AB - Gastric dilatation was experimentally induced in 6 anesthetized dogs maintained with constant-dose isoflurane in oxygen. An intragastric balloon was used to distend the stomach with a constant 30 mm of Hg pressure for 3.5 hours. The PaCO2 was maintained between 35 and 45 mm of Hg, using intermittent positive-pressure ventilation. Cardiopulmonary measurements prior to stomach distension (baseline) were compared with measurements taken during 0.1, 0.5, 1.0, 1.5, 2.5, and 3.5 hours of stomach distension by analyzing the change from baseline in a randomized block analysis with each dog as a block. After distending the stomach, cardiac index increased (P less than 0.01) from 1.5 to 3.5 hours. Stroke volume did not change, thus the increase in the cardiac index was attributable to an increase in heart rate. During inflation, increases were observed in systemic arterial, pulmonary arterial, and right atrial pressure. Respiratory frequency was unchanged; however, to maintain PaCO2 constant, it was necessary to progressively increase peak airway pressure. Although PaO2 tended to decrease during gastric dilation, the dogs were never hypoxemic. These results indicate that when our methods are used to maintain a constant anesthetic dose of isoflurane in oxygen, an observed increase in cardiovascular performance is expected. This differs from other studies in anesthetized dogs that have shown reduction in cardiovascular performance following gastric dilatation. PMID- 1626786 TI - Purification of a protein from serum of cattle with hepatic lipidosis, and identification of the protein as haptoglobin. AB - A protein that has 2 subunits with molecular weight of 35,000 and 23,000 was detected in serum of cattle with hepatic lipidosis (fatty liver). The protein was purified from serum obtained from a cow with fatty liver, and was identified as haptoglobin, which is known to have hemoglobin-binding capacity and to be an acute-phase protein. To assess the relevance of haptoglobin in fatty liver, cattle were classified in 3 groups (healthy control, haptoglobin-positive, and haptoglobin-negative); liver triglyceride content and several serum biochemical variables were evaluated for the 3 groups. Compared with the control and haptoglobin-negative cattle, haptoglobin-positive cattle had significantly (P less than 0.01) higher liver triglyceride content, serum bilirubin concentration, and aspartate transaminase activity. Serum haptoglobin concentration was high in slaughter cattle (27 of 40 cattle tested), particularly in cows (20/28). PMID- 1626785 TI - Hematologic values in newborn beef calves. AB - Hematologic values were determined in 35 beef calves at birth, at 24 and 48 hours, and in 22 of these calves at 3 weeks after birth. Thirty calves did not have clinical signs of disease throughout the 3-week period. Variables that changed significantly over time in these healthy calves included hematocrit, RBC count, hemoglobin concentration, mean cell volume, mean cell hemoglobin concentration, WBC count, neutrophil-to-lymphocyte ratio, and plasma total protein and serum immunoglobulin concentrations. Of the 35 calves, 5 had clinical signs of disease at 3 weeks. Comparison of hematologic values from these calves with values for healthy calves revealed significant differences at each sample collection time, although disease was not evident at the 3 early sample times. The band neutrophil count and the neutrophil-to-lymphocyte ratio differed between the 2 groups at birth. At 24 hours, the monocyte count was higher in the 5 ill calves. At 48 hours, total leukocyte, mature neutrophil, and monocyte counts, and neutrophil-to-lymphocyte ratio also were higher in the 5 calves. At 3 weeks when clinical signs of disease were detectable in the 5 calves, the total leukocyte, band neutrophil, and mature neutrophil counts, neutrophil-to-lymphocyte ratio, and plasma total protein and fibrinogen concentrations were higher.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626787 TI - Measurement of serum myoglobin concentrations in horses by immunodiffusion. AB - Quantitative immunodiffusion in one dimension was performed in 6-mm Duran tubes containing a 1% Nobel agar solution and various dilutions of antisera. A series of dilutions of pure myoglobin in equine sera as well as plasma from horses with rhabdomyolysis were tested. Standard curves were prepared of the migration distance of the formed precipitate from the meniscus of the gel after 3, 6, 12, and 24 hours. The clearest line of precipitate was formed with a 1:20 dilution of antisera in agar. Standard curves were nonlinear and plasma myoglobin could be detected at 2 micrograms of myoglobin/ml or greater. The test was optimal, with an error of 5.6%, when read at 24 hours at approximately 25 C. Tubes with agar could be stored for 6 months at 4 C without affecting the accuracy of the test. The specificity of myoglobin for skeletal or cardiac muscle, and its rapid clearance from serum after muscle necrosis, make it ideally suited for evaluating acute muscle damage and for testing the susceptibility of horses for rhabdomyolysis following an exercise test. PMID- 1626788 TI - Isolation and characterization of alpha 1-acid glycoprotein from horses, and its evaluation as an acute-phase reactive protein in horses. AB - Equine alpha 1-acid glycoprotein (alpha 1AG) was isolated from equine serum by successive ammonium precipitation, anion- and cation-exchange chromatographies, and gel filtration. Purified equine alpha 1AG had a molecular weight of 46,000 +/ 1,000, and contained 31.4% carbohydrate. Gel isoelectric focusing revealed an isoelectric point range of 2.8 to 3.7. With immunoelectrophoresis, it was found that alpha 1AG migrated to the alpha 1-globulin region. Single radial immunodiffusion was used for quantitative measurement of alpha 1AG in equine serum. In clinically normal foals, serum alpha 1AG was undetectable (less than or equal to 20 micrograms/ml) in less than or equal to 7-day-old foals, but was detected by 14 days. The alpha 1AG concentration (mean +/- SD) increased to reach mean adult values of 99.23 +/- 26.90 micrograms/ml by 1 year of age. The alpha 1AG concentration in pregnant mares decreased at 2 to 3 months before parturition, then gradually increased until 1 day after parturition, when a brief decrease was observed. The concentration increased again at 2 weeks after foaling, then a decrease was observed, after which the alpha 1AG concentration increased again by 2 to 4 months after parturition. The concentration of serum alpha 1AG quickly rose to peak values 2 to 3 days after castration and jejunojejunostomy in adult horses, returning to baseline values by 14 to 28 days after surgery. The alpha 1AG was concluded to be an acute-phase reactive protein in horses. PMID- 1626789 TI - Viscosity and rheologic properties of blood from clinically normal horses. AB - Blood viscosity (BV) was measured in 32 healthy horses at 6 spindle speeds (60, 30, 12, 6, 3, and 1.5 rpm) and for PCV of 40%, using a digital rotational cone and plate microviscometer. Also, in 7 of 32 horses, BV was measured 3 times each, for 3 PCV values (20, 40, and 60%), and at each spindle speed to determine effect of PCV on BV and machine and among-horse variations. Total plasma protein and fibrinogen concentrations were measured in all horses, using a standard refractometer and heat precipitation, respectively. In 7 of 32 horses, quantitative fibrinogen concentration was measured, using a quantitative fibrinogen assay. Plasma protein and fibrinogen concentrations were measured to determine their effect on BV. Plasma total protein (6.0 to 7.5 g/dl) and fibrinogen (100 to 400 mg/dl) concentrations were within normal reference range for our laboratory.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626790 TI - Comparative virulence of Haemophilus parasuis serovars 1 to 7 in guinea pigs. AB - Reference strains for Haemophilus parasuis serovars 1 to 7 were examined for virulence by inoculation of guinea pigs. Guinea pig response to intraperitoneal inoculation was similar for the 7 reference strains. However, apparent differences in virulence were detected after intratracheal inoculation. Cells of the references strains for serovars 1 and 5 were most invasive, causing moribundity or death at higher doses and a persistent septicemia at lower doses. Haemophilus parasuis could be isolated from respiratory and systemic sites; purulent bronchopneumonia, pericarditis, and pleuritis were apparent in infected guinea pigs. Inoculation of cells of the reference strains for serovars 2 and 6 also resulted in bronchopneumonia and moribundity or death in some guinea pigs; however, reisolation of H parasuis and microscopic lesions at necropsy were less pronounced than those observed with serovars 1 and 5. Inoculation of cells of serovars 3, 4 and 7 induced only transient clinical signs and minimal evidence of H parasuis infection at necropsy. The data from intratracheal inoculation of guinea pigs are similar to data from other investigations in swine, indicating differences in the pathogenic potential of H parasuis strains. Thus, guinea pigs may be useful as a laboratory animal model for examining cellular factors associated with virulence and immunogenicity of H parasuis. PMID- 1626791 TI - Microvascular circulation of the small intestine in horses. AB - The microvascular anatomic features of the small intestine was described by correlating results of microangiography, light microscopy, gross studies, and scanning electron microscopy of vascular replicas in 14 horses. After heparinization, the horses were euthanatized, a length of jejunum was transected, and blood was flushed free of the circulation, using isotonic NaCl solution. In six horses, the circulatory system was perfused with a modified radiopaque medium and evaluated radiographically. These sections were then evaluated by standard histologic methods. Sections from 8 horses were perfused with 1 of 2 types of plastics and studied grossly or by scanning electron microscopy. The marginal arterial arcade gives rise to vessels that enter the jejunum at the mesenteric angle. These vessels penetrated either directly, by branching and entering on both sides of the mesenteric angle, or supplying only 1 side of the mesenteric angle. All these vessels continued in the submucosa branching extensively, forming a submucosal plexus. This submucosal plexus supplied the tunica muscularis, tunica serosa, and the mucosa. Vessels within the 2 muscle layers ran parallel to the muscle fibers and, consequently, perpendicular to each other. The arterial supply to the mucosa penetrated the muscularis mucosae and branched to supply 2 mucosal capillary networks. An eccentrically placed arteriole penetrated the base of the villus and spiralled to the tip where it "fountained" into a mesh like capillary network, which descended peripherally in the villus to drain via 1 to 3, but most commonly 2 venules. Venules from adjacent villi united and drained via the submucosal veins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626792 TI - Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. AB - Activation of lymphocyte subpopulations was determined in conjunction with levels of cytokines in peripheral blood and bronchoalveolar lavage (BAL) of asthmatics. Allergic asthmatics had increased numbers of CD4+ IL-2R+ T cells in peripheral blood and BAL, and T-cell activation closely correlated with numbers of low affinity IgE receptor (CD23) bearing B cells. In contrast, in nonallergic asthmatics both CD4+ and CD8+ T cells from blood and BAL had increased expression of IL-2R, HLA-DR, and VLA-1. Furthermore, in the nonallergic asthmatics CD8+ T cells were decreased in blood but increased in BAL. Cytokine levels were determined in BAL fluid and supernatants from purified peripheral blood T cells and enriched BAL lymphocyte preparations. Allergic asthmatics were characterized by increased levels of IL-4 and IL-5, and this elevated IL-4 contributed to the elevated IgE levels found in these allergic subjects. In contrast, nonallergic asthmatics had elevated levels of IL-2 and IL-5, with IL-2 contributing to T-cell activation. In both types of asthma, the close correlation of IL-5 levels with eosinophilia suggests that IL-5 is responsible for the characteristic eosinophilia of asthma. Thus, we provide evidence of distinct T-cell activation resulting in different spectra of cytokines in allergic and nonallergic asthma. PMID- 1626793 TI - Ventilatory and metabolic responses to acute hyperoxia in newborns. AB - Hyperoxia has previously been found to increase metabolic rate (oxygen consumption [VO2] and CO2 production [VCO2]) in newborn mammals. We asked whether the same occurs in the newborn infant. Breathing pattern was measured in 25 full term infants, 1 to 2 days of age, from the spirometric record obtained with a pneumotachograph attached to a face mask. Concentrations of O2 and CO2 were continuously measured at the mouth; VO2 and VCO2 were computed as the product of VE and the difference between inspired and expired concentration of the respective gases, 5 min of air (FIO2 = 0.21) and 5 min of O2 (FIO2 = 1). A bias flow through the mask and pneumotachograph delivered the inspired gas and eliminated the effects of the instrumental dead space. In neither case did measurements at 1 min significantly differ from those taken at 5 min. In hyperoxia VE increased in 22 of the 25 infants, in average +18% (p less than 0.001, paired two-tailed t test). Because of a rise in tidal volume (+35%, p less than 0.001) and a decrease in breathing rate (-11%, p less than 0.005) alveolar ventilation (VA) increased by about 58% (p less than 0.001). VO2 and VCO2 increased by 25% and 17%, respectively (p less than 0.001). The rise in VO2 was too large to be explained by the greater respiratory work of the hyperventilation, whereas that of VCO2 was not large enough to fully explain the increase in VA. We conclude that in newborn humans, as in other newborn species, the normoxic metabolic rate seems to be limited by the availability of O2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626794 TI - Safety of bronchoalveolar lavage and bronchial biopsies in patients with asthma of variable severity. AB - The safety of fiberoptic bronchoscopy, bronchoalveolar lavage (BAL), and bronchial biopsies has been questioned in asthma, and current recommendations indicate that bronchoscopies should only be performed in mild to moderate asthma. Moreover, in most studies patients receive premedication with nebulized bronchodilators that may enhance the safety of the procedures. The purpose of this study was to determine (1) whether the overall safety of fiberoptic bronchoscopy, BAL, and bronchial biopsies in mild to moderate asthma could be extended to patients with more severe asthma and (2) whether these procedures are safe without premedication with nebulized bronchodilators. A group of 50 patients with asthma of variable severity (FEV1 ranging from 37 to 107% of predicted values) and 25 healthy volunteers were studied. Bronchoscopy, BAL (250 ml), and four bronchial biopsies were performed in a standardized manner, without premedication with a nebulized bronchodilator, by the same investigator. Safety was assessed by clinical follow-up, continuous recording of arterial oxygen saturation during the procedure with a digital oximeter, and measuring FEV1, FEF25-75, and FVC just before and 5 min after bronchoscopy. Arterial oxygen saturation decreased in asthmatic patients from 97% (range 91 to 99%) (T1) to 92% (range 79 to 98%) (T8) (ANOVA, Fisher's PLSD) and in control subjects from 97% (range 94 to 99%) (T1) to 93% (range 88 to 98%) (T8) (ANOVA, Fisher's PLSD). The fall in arterial oxygen saturation was not significantly different between asthmatic and normal subjects, and there was no correlation between arterial oxygen desaturation and the severity of asthma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626796 TI - Increase in airway responsiveness and effect of deep inhalation on airway caliber in allergen-induced asthma. Relationship to the late-phase response. AB - The airway responsiveness to methacholine (MCh) and the effect of deep inhalation (DI) on airway caliber were determined in 18 asthmatic patients at baseline and 3 and 24 h after an allergen inhalation challenge. The dose of MCh causing a 20% fall of FEV1 (PD20) was used as an index of airway responsiveness; the ratio of forced expiratory flow at 40% of FVC from maximal and partial flow/volume curves (MEF40M/P) was used to assess the effect of DI on airway caliber. Thirteen patients showed a dual asthmatic response (DAR) to allergen, 5 patients an isolated early-phase asthmatic response (EAR). In the DAR patients, 3 h after allergen challenge, when the early-phase response had resolved and the late-phase response had yet to develop, MChPD20 (geometric mean) was reduced from 202 to 71 micrograms (P less than 0.001) whereas MEF40M/P at the MCh end point was unchanged (p greater than 0.4). Twenty-four hours after allergen challenge, when late-phase response had developed, MChPD20 was further reduced to 51 micrograms (p less than 0.02), and this reduction was accompanied by a decrease of MEF40M/P at the MCh end point (p less than 0.01). In the EAR patients, neither MChPD20 nor MEF40M/P was significantly changed at any time during the study. We conclude that most of the increase in airway responsiveness that follows acute exposure to allergen precedes the late-phase response and is not determined by the same mechanisms that impair the ability of the lung to dilate airways with a DI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626795 TI - Different effects of nasal and bronchial glucocorticosteroid administration on bronchial hyperresponsiveness in patients with allergic rhinitis. AB - Disorders of the upper respiratory tract, particularly allergic rhinitis, are commonly associated with bronchial hyperresponsiveness. The latter may be due to postnasal drip or to mediator or chemotactic factors into the lower airways that either directly alter airway reactivity or cause airway inflammation. The aim of this study was to compare the effect of an identical dose of nasal or bronchial corticosteroid administration on bronchial hyperresponsiveness in patients with allergic rhinitis. Eleven patients were studied. All of them were judged atopic on the basis of positive skin tests to common allergens. During control, spirometry, flow-volume curves, and specific airway conductance (SGaw) were measured. Bronchial challenges were then performed with increasing concentrations of carbachol, and dose-response curves were constructed. The concentration of carbachol that decreased SGaw by 35% from baseline (PD35) was determined by interpolating from the dose-response curve. Control measurements were repeated at 1-wk intervals to ensure that PD35 was stable in all the patients. Then the patients received for 2 wk, in a double-blind randomized crossover fashion, a topical administration of either an aerosol of 400 micrograms of beclamethasone dipropionate (B) into the nose (100 micrograms four times per day) or into the bronchi. During each trial period, identical sprays of placebo were used, the latter being administered into the nose when B was administered into the bronchi and vice versa. Measurements were then performed after 2 wk of intranasal administration and after 2 wk of intrabronchial administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626797 TI - Histamine tachyphylaxis in human airway smooth muscle. The role of H2-receptors and the bronchial epithelium. AB - The role of airway epithelium and H2-receptors in the development of histamine tachyphylaxis was studied using human isolated bronchial smooth muscle strips obtained from 18 patients undergoing thoracotomy. In epithelium-intact strips, a 38% reduction in the maximal contractile response (Emax) (p less than 0.002) and a 2.14-fold increase in the EC50 (p less than 0.02; n = 18) was observed after three separate histamine cumulative concentration effect curves (CCEC). In contrast, significant differences were not seen for either Emax (p greater than 0.4; n = 10) or EC50 (p greater than 0.26; n = 10) in epithelium-denuded strips. In separate experiments, both intact and denuded muscle strips were treated with the H2-receptor antagonist ranitidine (60 microM), either 30 min prior to the first or 30 min prior to the second histamine CCEC. In epithelium-intact strips, pretreatment with ranitidine caused a 1.8-fold increase in Emax in the initial CCEC (p less than 0.02), and both ranitidine schedules prevented tachyphylaxis (n = 8). In epithelium-denuded preparations, ranitidine did not enhance the responsiveness to histamine beyond that seen in untreated epithelium-denuded strips (n = 6). These data suggest that histamine-induced tachyphylaxis occurs in human airway smooth muscle and is mediated, at least in part, via H2-receptors resident on airway epithelium. In vivo, this may function as a protective mechanism, but damage to the epithelium and loss of H2-receptors may be significant in the development of histamine bronchial hyperreactivity as seen in asthma. PMID- 1626798 TI - Effect of interleukin-2 on the airway response to antigen in the rat. AB - To evaluate the hypothesis that lymphocyte stimulation can modify the bronchoconstrictive response to inhalational challenge with an allergen, we administered interleukin-2 (IL-2), an important lymphokine in lymphocyte activation and proliferation, to actively sensitized rats. Brown Norway rats received either human recombinant IL-2 (n = 8) or its vehicle (n = 7) twice a day from the ninth to the fourteenth day after active sensitization to ovalbumin (OA) and were challenged with an aerosol of OA. Lung resistance (RL) during the early response increased to a maximum of 698 +/- 230% and 180 +/- 26% of baseline values in the animals receiving IL-2 and vehicle, respectively (p less than 0.025). The late response was threefold greater in IL-2-treated than in vehicle treated animals (p = 0.01). IL-2 increased OA-specific IgG levels in the serum, but it did not significantly affect total or specific IgE levels. IL-2 caused an inflammatory infiltrate around the airways with significant increases in eosinophils, lymphocytes, and mast cells prior to antigen challenge. Our results indicate that stimulation of cell-mediated immunity can affect airway responsiveness to antigen. PMID- 1626799 TI - Immunohistology of the nasal mucosa following allergen-induced rhinitis. Identification of activated T lymphocytes, eosinophils, and neutrophils. AB - We have studied the immunohistology of the nasal mucosa in allergen-induced rhinitis. Sixteen grass pollen-sensitive patients were challenged twice by randomly allocated allergen or control solutions applied on filter paper disks to the inferior turbinate. All had immediate nasal responses, but late-phase responses were equivocal and only evident as nostril blockage. When cell counts in the nasal submucosa were compared with control values 24 h after allergen, there were no changes in CD45+ (total leukocytes), CD3+, or CD8+ cells. Significant increases were found in the numbers of CD4+ T-helper cells (p less than 0.05) and CD25+ [interleukin-2 receptor (IL-2R+)] cells (p less than 0.02). Increases in eosinophils (anti-major basic protein, p less than 0.01) and neutrophils (antineutrophil elastase, p less than 0.01) were also observed. There were increases in tissue macrophages and HLA-DR-positive immunostaining and a reduction in mast cells (tryptase positive), but none of these changes was statistically significant. No significant changes in epithelial thickness, cross sectional area, or integrity were observed. There was a significant correlation between CD4+ and CD25+ cells (r = 0.61, p less than 0.01) but not between macrophages and CD25+ cells (r = 0.18). The changes in the nasal submucosa were not merely a reflection of alterations in circulating cell populations since it was shown that a significant increase in the lymphocyte CD4/CD8 ratio (p less than 0.05) was observed in nasal biopsies but not in peripheral blood after allergen challenge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626800 TI - Latent adenoviral infection in the pathogenesis of chronic airways obstruction. AB - Childhood infection of the respiratory tract has been proposed as an independent risk factor in the pathogenesis of the chronic obstructive pulmonary disease (COPD) that develops in cigarette smokers. The present study examines adult lung tissue for latent adenoviral DNA because many of its 41 serotypes cause childhood respiratory disease and the virus is known to persist in other tissues in a latent form. Lung tissue resected for solitary nodules from 20 patients with airways obstruction and 20 patients without airways obstruction, matched for age, sex, and smoking history, were compared to determine whether adenoviral DNA is more commonly found in patients with COPD. The polymerase chain reaction (PCR) was used to examine two widely separated segments of the adenoviral genome. In situ hybridization (ISH) was performed using a probe covering the entire viral genome to determine the types of cell infected by the virus. The PCR analysis showed that a 675 base pair target sequence of the E1A region of the adenovirus was present in most of the lungs studied with greater copy numbers in the smokers with airways obstruction in both paraffin-embedded (p less than 0.002) and frozen lung tissue (p less than 0.016), whereas the E3/19K region showed no difference between the groups. When sufficient copy numbers were present to localize the DNA by ISH it was found in epithelial cells of the smokers who had airways obstruction. These data are consistent with a current model of adenoviral integration into host DNA and suggest that the E1A region of the adenovirus may contribute to the pathogenesis of COPD. PMID- 1626801 TI - Hydatid disease of the lungs. Study of 386 cases. AB - During a 10-yr period, 386 patients with hydatid disease of the lung were treated at our hospital. There were 165 male and 221 female patients with a mean age of 30.15 + 16.9 yr. There were 286 solitary, 20 multiple, and 21 bilateral cysts. In 59 patients, the cysts included the lung and other organs; in 54, the lung and the liver; in four, the lung and the kidney; in one, the lung and the peritoneum. Diagnosis was made using clinical criteria, serologic findings, and imaging techniques; 373 patients were treated surgically. Surgical procedures consisted of cystectomy in 93 patients, pericystectomy in 166 patients, and lung resection in 114 patients. Mebendazole and flubendazole were used in three patients. Postoperative complications occurred in 44 patients (15.8%). There were two operative deaths (mortality rate, 0.53%). Patients have been followed yearly, with a median follow-up of 6 yr. Active hydatid disease has been found in two patients. PMID- 1626802 TI - Late effects of endotoxin on the accumulation and function of monocytes in rabbit lungs. AB - Recent studies from our laboratory show that the lung contains a marginated pool of monocytes. The present study was designed to investigate monocyte accumulation in this pool 4 to 28 h after a single dose of endotoxin when the endotoxin had disappeared from the circulation. This was accomplished by administering a single intravenous dose of endotoxin (Escherichia coli, 50 micrograms/rabbit) to unanesthetized animals (n = 6) and saline to controls (n = 5) at time 0. Four hours after this dose of endotoxin, 111In-monocytes (93.5% pure) isolated from donors were injected intravenously, and, at 27 h, the rabbits were anesthetized and colloidal carbon (CC, 1 ml/kg body weight) was injected intraarterially to provide a phagocytic stimulus. The animals were sacrificed at 28 h, and the lungs were fixed in situ with glutaraldehyde. The data show that lungs from the endotoxin-treated rabbits contained 4.8 times more 111In-monocytes than controls, that 92% of these radiolabeled monocytes were in the alveolar capillaries, and that 72% of these labeled cells had phagocytosed CC. The histologic studies of unlabeled cells confirmed that this endotoxin treatment caused a 3-5-fold increase in unlabeled mononuclear cells and neutrophils (PMN) in the microvasculature and that many of the unlabeled monocytes in the endotoxin treated group had also phagocytosed colloidal carbon. The behavior of the donor monocytes injected after the endotoxin had time to disappear from the circulation suggests that they accumulate in the lung in response to the indirect effects of endotoxin on endothelial cells. PMID- 1626803 TI - Erythromycin reduces neutrophils and neutrophil-derived elastolytic-like activity in the lower respiratory tract of bronchiolitis patients. AB - Diffuse panbronchiolitis (DPB) is a disease of adults characterized by chronic inflammation of the respiratory bronchioles and the infiltration of chronic inflammatory cells. The clinical efficacy of erythromycin therapy has been demonstrated in DPB patients, but the mechanism of action of this drug is unknown. We investigated the localization of neutrophils in lung biopsy specimens, as well as the cell population and elastolytic-like and chemotactic activity of bronchoalveolar lavage (BAL) fluid, before and after treatment with erythromycin or ampicillin in 11 DPB patients (six biopsy-proven and five clinically diagnosed) and one follicular bronchiolitis patient. These bronchiolitis patients had a high percentage of neutrophil and a high neutrophil derived elastolytic-like activity in BAL fluid compared with chronic bronchitis patients and normal control subjects. The number of neutrophils and the neutrophil-derived elastolytic-like activity in BAL fluid decreased significantly after treatment with erythromycin along with a significant improvement in pulmonary function studies, although there was no significant change in the chemotactic activity of BAL fluid. No significant reduction in BAL fluid neutrophilia was found in the ampicillin-treated patients. These results suggest an important role for the neutrophil in the pathogenesis or development of bronchiolitis, and also suggest that erythromycin may be useful for the treatment of bronchiolitis through its direct action upon host phagocytic cells. PMID- 1626804 TI - Re-targeting ventilatory objectives in adult respiratory distress syndrome. New treatment prospects--persistent questions. PMID- 1626805 TI - Risk factors for the degradation of lung elastic fibers in the ventilated neonate. Implications for impaired lung development in bronchopulmonary dysplasia. AB - In order to evaluate the risk for proteolytic destruction of lung parenchymal elastic fibers in ventilated premature infants, the concentrations of elastase were determined in tracheal aspirates of 65 infants from whom we obtained a total of 327 sequential samples. Elastase was detected at least once in 39 of the 65 infants studied. Eleven of these infants were ventilated with greater than 60% oxygen for greater than 5 days. In 19 infants, the presence of elastase was associated with positive bacterial and/or viral cultures and/or elevated ratios (greater than 0.22) of immature neutrophils to total neutrophils. Elastase was not detected in the lung secretions of 26 infants ventilated with greater than 60% oxygen for less than 3 days, suggesting minimal risk for elastic fiber destruction in the intubated infant who neither has pneumonia nor requires prolonged hyperoxic ventilation. The risk for elastic fiber destruction was further evaluated by analyzing sequential urine and tracheal aspirate samples for the presence of an elastolytic degradation product of elastin (desmosine). The biochemical data indicated a potential risk for proteolytic destruction of elastic fibers in association with infection and/or prolonged hyperoxic exposure. In addition, autopsy specimens obtained from three of the infants revealed structurally abnormal lung parenchymal elastic fibers. Because elastic fibers are believed to provide the structural support for alveolar septal development, proteolytic degradation of these fibers may be a significant factor in the impaired lung development that occurs in infants with bronchopulmonary dysplasia. PMID- 1626807 TI - Pulmonary vasculitis in Behcet's disease. AB - Clinical findings of 12 patients with Behcet's disease and lung involvement are presented. Male to female ratio was 11/1, mean age was 35.3 +/- 8.8 yr. All patients had at least four other organ manifestations of vasculitis, either in their history or during the period of lung involvement. The main complaint was hemoptysis of varying degree in 11 of the 12 patients. The chest X-ray films showed unilateral hilar enlargements in six patients, diaphragm elevation in four, horizontally or obliquely oriented linear opacities in three, diffuse, ill defined infiltrates in upper and lower zones in three, wedge-shaped peripheral opacities in one, and bilateral pleural effusion in one patient. Computed tomography of the chest performed in nine patients revealed aneurysms, narrowings, and cutoffs of the main, lobar, segmental, or peripheral branches of the pulmonary artery and irregular configuration of other pulmonary vessels. Perfusion scans demonstrated defects of various sizes in all patients. Pulmonary angiography performed in only two patients showed amputation of branches of the pulmonary artery and aneurysmal dilatations. The patients were treated with a combination therapy consisting of corticosteroid, cyclophosphamide, colchicine, and antiaggregants, with very good results in the short term. PMID- 1626806 TI - Increased pulmonary artery elastolytic activity in adult rats with monocrotaline induced progressive hypertensive pulmonary vascular disease compared with infant rats with nonprogressive disease. AB - In a rat model of pulmonary hypertension induced by monocrotaline, medial hypertrophy of the pulmonary arteries is associated with enhanced production (synthesis) of insoluble elastin relative to accumulation and an increased number of elastin fragments, features suggestive of an elastolytic process. In the present study, we measured and characterized pulmonary artery (PA) elastolytic activity at time points before as well as coincident with the progression of medial hypertrophy in monocrotaline-injected adult male Sprague-Dawley rats. We also determined whether medial hypertrophy is preceded by ultrastructural changes in elastin. Since medial hypertrophy develops but fails to progress in rats injected with monocrotaline at 8 days of age, we assessed whether, compared with adult rats, there were also structural and biochemical differences in elastin and elastolytic activity. A twofold increase in elastolytic activity per milligram tissue was observed 2 days after monocrotaline injection in adult rats (p less than 0.01), and there was an increased number of breaks in the internal elastic lamina (IEL) at 4 days (p less than 0.05) (i.e., before the development of medial hypertrophy). Associated with the progression of medial hypertrophy between 16 and 28 days after monocrotaline injection, there was a further threefold increase in elastolytic activity per milligram tissue by 28 days (p less than 0.01). Susceptibility of the elastolytic activity to specific inhibitors suggested that one or more serine elastases is involved. In infant rats in which medial and right ventricular hypertrophy fail to progress in severity between 16 and 28 days after monocrotaline injection, we did not measure an increase in elastolytic activity, nor was there evidence of an increase in the number of breaks in the IEL at 4 days, suggesting a lack of increased elastolytic activity at an earlier time point. The total content of PA elastin in infant rats, although increased compared with control rats (p less than 0.01), was not associated with heightened production and appeared ultrastructurally as thicker laminae (p less than 0.05) rather than as fragments previously reported in adult rats. PMID- 1626808 TI - Diseases of the small airways. PMID- 1626809 TI - Effect of steroids on diaphragm of newborn, weanling adolescent, and adult rats. AB - The purpose of this study was to compare the effects of dexamethasone on the rat diaphragm during the postnatal period and into adulthood. Groups of 48 newborn, 60 weanling adolescent, and 60 adult rats were either (1) treated with DXM (ST, steroid-treated animals) or (2) untreated and pair-fed (C, control animals). After birth, 24 newborn rats were kept with their mother, which received a daily intramuscular injection of 0.5 mg/kg body weight of dexamethasone for 2 wk. Groups of thirty weanling adolescent and 30 adult rats were treated with 1 mg/kg/day of dexamethasone given intramuscularly for 2 wk. Diaphragm performance was compared between ST animals and age-matched C animals. Weights of the body, the diaphragm, the extensor digitorum longus (EDL), and the soleus were obtained. Diaphragm strips were studied in an in vitro preparation to assess contractile and endurance properties. In all the ST animals, body and total diaphragm weights were reduced compared with age-matched C animals (p less than 0.001). In newborn and weanling adolescent ST animals, loss in diaphragm weight was slightly less than in limb muscles, in contrast to adult animals (p less than 0.05). However, diaphragms from adult and weanling adolescent ST animals showed unaffected twitch characteristics, normalized force-frequency curves, and endurance capacity. In the meantime, in newborn ST animals, diaphragm atrophy was associated with significantly decreased force normalized for fiber cross-sectional area and muscle weight (p less than 0.01) and decreased endurance capacity (p less than 0.05). We conclude that the effects of DXM on the diaphragm depend on the developmental status of the muscle at the time of drug administration. PMID- 1626810 TI - Interleukin-5 modulates eosinophil accumulation in allergic guinea pig lung. AB - Based on its involvement in eosinophil biology, interleukin 5 (IL-5) may play a role in the pulmonary eosinophilia associated with allergic reactions. We have examined that hypothesis using a neutralizing antibody to IL-5 in ovalbumin sensitized guinea pigs challenged with aerosolized antigen. The extent of eosinophilia has been quantitated in bronchoalveolar lavage (BAL) and by histologic evaluation of lung tissue sections. Acute intraperitoneal administration of a rat IgG, monoclonal antibody to murine IL-5 derived from TRFK 5 cells prevented lung and BAL eosinophilia in a dose-dependent fashion at and above 10 micrograms per guinea pig. Treatment with either an experimentally irrelevant, isotype-matched antibody from GL113 cells or with heat-denatured IL-5 antibody was without effect. These studies demonstrate the importance of IL-5 to pulmonary eosinophilia in challenged, allergic guinea pigs. PMID- 1626811 TI - Extracutaneous manifestations of Sweet's syndrome: steroid-responsive culture negative pulmonary lesions. PMID- 1626812 TI - Effects of positive end-expiratory pressure on the canine venous return curve. AB - To study the mechanism whereby positive end-expiratory pressure (PEEP) decreases venous return, we used a closed-chest canine venous bypass preparation to study the effects of 10 mm Hg PEEP on the systemic venous pressure-flow curves from the superior and inferior vena cava (SVC and IVC). These curves were characterized by three variables: the critical downstream pressure below which venous return was maximal (PCRIT), the conductance to venous return (GVR), and the effective upstream pressure driving venous return. PEEP reduced venous return by decreasing the maximal venous return even when the pressures at the outflow of the IVC and SVC were maintained below zero. PEEP increased PCRIT in the SVC and IVC (SVC: 0.31 +/- 0.53 to 3.21 +/- 0.84; IVC: -0.41 +/- 0.64 to 5.23 +/- 1.02 (SE) mm Hg; p less than 0.005). GVR in the SVC was reduced (52.5 +/- 26 to 37.8 +/- 5.3 (SE) ml/min/mm Hg; p less than 0.005), but changes in the IVC did not reach statistical significance. These changes were partially offset by increases in the upstream pressure driving venous return (SVC: 9.44 +/- 0.54 to 12.25 +/- 0.71; IVC: 9.42 +/- 0.69 to 12.51 +/- 1.02 (SE) mm Hg; p less than 0.01). Analysis of these findings suggests that PEEP may alter venous return through effects on the peripheral circulation, independent of its effects on the heart. PMID- 1626813 TI - Lung inflammation in coal miners assessed by uptake of 67Ga-citrate and clearance of inhaled 99mTc-labeled diethylenetriamine pentaacetate aerosol. AB - We compared the diffuse lung uptake of 67Ga-citrate, an index of inflammatory lung activity, with the lung clearance of inhaled 99mTc-labeled diethylenetriamine pentaacetate (DTPA) aerosol, an index of pulmonary epithelial permeability, in a group of 19 West Virginia coal miners whose pulmonary status was compatible with coal worker's pneumoconiosis. 99mTc-DTPA clearance alone and 67Ga-citrate uptake alone were measured in nine and five additional subjects, respectively. The objective of this study was to determine if increased 99mTc DTPA lung clearance was caused by inflammation at the lung epithelial surfaces. Subjects inhaled approximately 150 microCi (approximately 5.6 MBq) of 99mTc-DTPA aerosol, and quantitative gamma camera images of the lungs were acquired at 1-min increments for 25 min. Regions of interest (ROI) were selected to include (1) both lungs; (2) each individual lung; and (3) the upper, middle, and lower thirds of each lung. 99mTc-DTPA clearance was determined from the slopes of the respective time-activity plots for the different ROI. Each subject was intravenously administered 50 miCroCk (1.9 MBq)/kg 67Ga-citrate 48 to 72 h before imaging the body between neck and pelvis. The extent of 67Ga-citrate lung uptake was expressed as the gallium index (GI). Mean radioaerosol clearance half-time (T1/2) for the six nonsmoking coal miners (60.6 +/- 16.0 min) was significantly shorter (p less than 0.001) than for the nonsmoking control group (123.8 +/- 28.7 min). T1/2 for the 12 smoking miners (18.4 +/- 10.2 min) was shorter than for the smoking control group (33.1 +/- 17.8 min), but the difference did not attain statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626814 TI - Pulmonary tuberculosis in Kigali, Rwanda. Impact of human immunodeficiency virus infection on clinical and radiographic presentation. AB - The aim of the present study was to compare the clinical and radiographic presentation as well as the therapeutic outcome of pulmonary tuberculosis (PT) in adult patients with and without human immunodeficiency virus type 1 (HIV-1) infection in Kigali, Rwanda. Over a 17-month period 59 consecutive patients with bacteriologically and/or histopathologically documented PT were enrolled. Of these, 48 (81%) patients were HIV seropositive. Among these, 35 fit the WHO clinical criteria for AIDS (WHOCCA) at the time of admission. Significant differences were found between the HIV-seropositive and HIV-seronegative groups of patients: fever (85 versus 36%; p less than 0.001), tuberculin skin test anergy (69 versus 0%; p less than 0.01), mediastinal and/or hilar adenopathies (31 versus 0%; p = 0.05), and pleural effusion (43 versus 9%; p less than 0.05) were more frequently encountered in the HIV-seropositive group, and upper lobe infiltrates (55 versus 16%; p less than 0.02) and cavitation (91 versus 39%; p less than 0.003) were more often seen in the HIV-seronegative group. However, HIV seropositive patients not meeting WHOCCA were less frequently anergic (0 versus 100%; p less than 0.001) and feverish (53 versus 97%; p less than 0.01) and more often had cavitation (69 versus 28%; p less than 0.02) and less often mediastinal and/or hilar adenopathies (7 versus 40%; p less than 0.04) compared with HIV seropositive patients meeting WHOCCA. Under antituberculosis treatment, clearance of fever was slower in HIV-seropositive compared with HIV-seronegative patients, and among the HIV-seropositive group it was slower in those fitting WHOCCA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626815 TI - Results of a directly observed intermittent isoniazid preventive therapy program in a shelter for homeless men. AB - We offered directly supervised isoniazid preventive therapy to middle-aged and elderly men who were exposed to tuberculosis during an outbreak of cases at a homeless shelter. Isoniazid, 900 mg, was administered twice weekly to men at the shelter and at the downtown Public Health Clinic. We report on compliance and adverse reactions associated with this preventive regimen. Isoniazid preventive therapy was offered to 64 men. Forty-seven men (73%) began therapy, and 23 of them (49%) completed the 6- to 12-month regimen. Men who failed to complete isoniazid therapy received a median of 11 biweekly doses (range, 1 to 41 doses) over a median of 9 wk (range, 3 to 37 wk). The most common reason for incomplete treatment was that the men no longer frequented the shelter. One hepatotoxic reaction occurred, for a 2.1% cumulative incidence among all men who started therapy and a 3.7% cumulative incidence among the 27 known alcoholic men who began therapy. In addition, we sought to identify personal characteristics of the men that might be associated with noncompliance. Out-of-state location of personal contacts in case of emergency was strongly associated with poor compliance. These data provide some assurance that directly supervised isoniazid preventive therapy may be offered safely to sheltered elderly men with a high prevalence of alcoholism. Further improvements in compliance with isoniazid preventive therapy in homeless populations may depend on the development of a therapeutic regimen of only 2 to 3 months duration. PMID- 1626816 TI - Nonfibrous mineral particles in bronchoalveolar lavage fluid and lung parenchyma from the general population. AB - It is recognized that bronchoalveolar lavage (BAL) gives access to particulate matter present at the surface of the peripheral airspace. The objective of the present study was to evaluate the ability of BAL fluid analysis to predict the lung parenchymal particulate content. A BAL fluid sample, the parenchyma sample having undergone BAL, and an adjacent parenchyma sample that had not undergone BAL were obtained at autopsy on 10 individuals without any known recent occupational exposure to mineral particles. The particles (larger than 0.1 micron) were analyzed using a transmission electron microscope equipped with a microanalysis system. Nineteen types of particles were distinguished. The distribution of particle types in the three samples was compared. No significant difference between the relative concentrations was found, except for two particle types: fly ash (excess in BAL fluid compared with lavaged lung) and kaolinite (excess in lavaged lung compared with adjacent area). Such differences may be due to limitations in methodology. Although no correlation could be found between the absolute concentrations of particles in BAL fluid and in lung tissue, analysis of particles in BAL fluid may provide information on the types of particles present in the lung parenchyma. PMID- 1626817 TI - Relationship between urinary cotinine level and diagnosis in children admitted to hospital. AB - The reported association between passive smoking and respiratory illness in children has been based on the parents' assessment of their own level of smoking. To more critically evaluate a causal relationship between passive smoking and childhood ill health, we used urinary cotinine, which is the major metabolite of nicotine and has a long half-life, to objectively quantitate the level of passive smoking in children. Urine was collected from 609 children (median age 3.8 yr, range 1 month to 17 yr) on admission to hospital; cotinine levels were obtained in 491 of these samples, and a comprehensive respiratory questionnaire was completed for 468 children. Statistical analysis was carried out on transformed data using both parametric and nonparametric statistics. Cotinine levels in the children correlated with the parents' current smoking (p less than 0.001). Elevated levels were found in the 41 children admitted with bronchiolitis compared with a group of a similarly aged children with nonrespiratory illnesses (p less than 0.02). Elevated levels were not found for any other diagnosis. We conclude that the urinary cotinine approach has provided objective evidence linking passive smoking to hospital admission for bronchiolitis in infants. PMID- 1626818 TI - Peak expiratory flow variability and bronchial responsiveness to methacholine. An epidemiologic study in 117 workers. AB - We studied the relationships between peak expiratory flow (PEF) variability and bronchial responsiveness to methacholine in 117 workers attending the annual compulsory examination (mean age, 38.7 yr +/- 9.5; men, 86.3%). Subjects recorded their highest PEF out of three, every 3 waking hours (i.e., five times a day) for 7 days, each using a newly purchased Vitalograph peak flow meter, and underwent methacholine challenge tests with a maximal cumulative dose of 1,200 micrograms. Those with a FEV1 fall of 15% or more were considered as reactors. The variability of PEF was expressed as the amplitude percent mean, calculated from daily amplitude (highest-lowest reading/mean reading of the day x 100), averaged over 6 days, from the second to the seventh. This index had a continuous distribution, skewed towards the greatest amplitudes, and correlated negatively with FEV1 (r = -0.25, p = 0.01). Subjects with asthma (n = 8) had greater variations. In the 109 nonasthmatics, greater variability was observed in subjects with wheeze apart from colds, breathlessness, or hay fever; the average amplitude was greater in reactors than in nonreactors to methacholine (16.9% versus 9.3%, p less than 0.001). The subjects with excessive PEF variability were all methacholine reactors, but they were only a subgroup of the reactors. These results provide evidence that excessive PEF variability is an indicator of bronchial hyperresponsiveness to methacholine in a population sample. PMID- 1626819 TI - Long-term prognosis of near-fatal asthma. A 6-year follow-up study of 145 asthmatic patients who underwent mechanical ventilation for a near-fatal attack of asthma. AB - The objective of the present study was to investigate the long-term prognosis of near-fatal asthma. A retrospective cohort study design was used. Cases were defined as any asthmatic individual requiring mechanical ventilation for the first time for an asthma exacerbation between January 1, 1983 and December 31, 1988. The consecutive sample of patients was drawn from four study sites, specifically four intensive care units (ICU), based in a large urban area (1 million inhabitants). These four ICU total approximately 5,000 admissions per year and are the referral centers for more than 95% of patients requiring respiratory intensive care in the area. Data collection was obtained by questionnaires addressed to the patients and to their attending physicians and was completed by telephone calls if necessary. A total of 147 patients entered the study. The long-term outcome could be evaluated in all but two patients. The follow-up period ranged from 1 to 75 months. In-hospital mortality was 16.5%. Among the 121 patients discharged from the ICU, 18 subsequently died, 17 of whom died from a new attack of asthma. Post-hospitalization mortality was 10.1% (95% CI, 5.9 to 16.8%) after 1 yr, 14.4% (CI, 9 to 22.3%) after 3 yr, and 22.6% (CI, 12.7 to 36.8%) after 6 yr. Nearly two-thirds (61.5%) of these secondary deaths occurred within the year following discharge from the ICU. Smoking was associated with a higher in-hospital mortality, as well as with a higher posthospitalization mortality. Age was also independently associated with a higher posthospitalization mortality. It is noteworthy that the secondary deaths were mostly observed in patients over 40 yr of age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626820 TI - Reproducibility of visual analog scale measurements of dyspnea in patients with chronic obstructive pulmonary disease. AB - The purpose of this study was to evaluate the reproducibility of visual analog scale ratings of the effort to breathe (VASe) and the degree of discomfort evoked by breathing (VASd) in patients with chronic obstructive pulmonary disease (COPD) during exercise. Six subjects with moderately severe COPD (FEV1 = 1.12 +/- 0.29 L, FEV1/FVC = 44 +/- 4%) underwent progressive incremental exercise testing to a symptom-limited maximum every week for 8 wk. VASe and VASd were highly correlated in each subject (r = 0.99 +/- 0.01). The slope of the VASd/VASe relationship for all trials in all subjects was not significantly different from 1, indicating that our subjects were rating a common sensation with the two scales. VASe at maximal exercise was reproducible in every subject; the within-subject coefficient of variation (CV) was 6% (range, 2 to 10%) and compared favorably with physiologic indices: 7% (range, 3 to 12%) for oxygen consumption and 10% (range, 5 to 16%) for minute ventilation (VI). In contrast, submaximal VAS ratings were highly variable. At 66% of the maximal work load, the within-subject CV for VASe was 21% (range, 11 to 28%) compared with 6% (range, 4 to 7%) for VO2 (p less than 0.003) and 10% (range, 5 to 16%) for VI (p less than 0.01). VASe correlated linearly with VI and VO2 in all subjects in all trials. However, within an individual subject the slope and position of these relationships varied widely between trials.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626821 TI - Effective site of bronchodilation by beta-adrenergic and anticholinergic agents in patients with chronic obstructive pulmonary disease: direct measurement of intrabronchial pressure with a new catheter. AB - To study the effective site of bronchodilators in patients with chronic obstructive pulmonary disease (COPD), a catheter tip micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a bronchus, 3 mm inner diameter, in 14 patients with COPD. We simultaneously measured mouth flow, transpulmonary pressure (PL) and intra-airway lateral pressure during quiet tidal breathing. Total pulmonary resistance (RL) was calculated from PL and mouth flow, and central airway resistance (RC) was calculated from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (RP) was obtained by the subtraction of RC from RL. This technique permitted identification of the site of changes in airway resistance. Atropine sulfate (5 mg/ml) was continuously inhaled during tidal breathing for 1 min by seven patients (Group A), and the other seven patients (Group B) inhaled fenoterol (1 mg/ml) for 1 min. The doses that were actually delivered were 0.75 mg for atropine sulfate and 0.15 mg for fenoterol. The baseline resistances of RC and RP were 3.9 +/- 0.8 and 3.7 +/- 0.6 cm H2O/L/s in Group A, and 4.3 +/- 0.5 and 3.5 +/- 0.4 cm H2O/L/s in Group B, respectively. Both atropine sulfate and fenoterol significantly decreased RL by an average of 2.4 and 2.6 cm H2O/L/s, and there was no significant difference between them (p greater than 0.20). The percentage decrease in resistance from the baseline values by fenoterol did not differ significantly between RC and RP (p greater than 0.20). However, atropine sulfate significantly decreased RC more than RP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1626822 TI - Peripheral airways resistance in smokers. AB - To determine peripheral airways resistance (Rp) in asymptomatic smokers, we used a wedged bronchoscope technique to study 19 volunteers (18 to 44 yr of age) who actively smoked for 2 to 28 pack-years. A fiberoptic bronchoscope was wedged in a subsegmental bronchus of the right upper lobe. Using a double lumen catheter inserted through the working channel of the bronchoscope, we infused 5% CO2 in air through one lumen and measured pressure through the second lumen. Rp was determined as the average of the peripheral resistance measured at three or more flow rates. This resistance ranged from 0.003 to 0.075 cm H2O/ml/min in the 19 subjects. We have previously shown normal subjects to have an average Rp of 0.009 +/- 0.002 cm H2O/ml/min (mean +/- SE) and asthmatic subjects an average of 0.069 +/- 0.017 cm H2O/ml/min. Thus, despite normal pulmonary function as assessed by spirometry, these asymptomatic smokers demonstrated a wide range of Rp values from normal to that observed in asthmatic subjects. These findings are consistent with a mechanism that considers the high resistance to result from inflammatory changes in the small airways. PMID- 1626823 TI - Regulation of oxytocin gene expression and forms of oxytocin in the brain. PMID- 1626824 TI - Control of synthesis and release of oxytocin in the sheep brain. PMID- 1626825 TI - Oxytocin and vasopressin. From genes to peptides. PMID- 1626826 TI - Increases in dendritic bundling and dye coupling of supraoptic neurons after the induction of maternal behavior. PMID- 1626827 TI - Evolutionary precedents for behavioral actions of oxytocin and vasopressin. AB - It is clear that the behavioral actions of oxytocin and vasopressin in mammals are not newly acquired, but have evolutionary antecedents. Injection studies with fish, amphibians, reptiles, and birds indicate that AVT can activate certain reproductive behaviors. The strongest evidence that AVT acts centrally to control reproductive behaviors comes from research on T. granulosa. In this amphibian, injections of AVT agonists activate courtship behaviors (amplectic clasping) in males and egg-laying behaviors in females, whereas injections of AVT antagonists inhibit the behaviors. Also, in Taricha males, AVT concentrations in specific brain areas are associated with the expression of courtship behaviors. Several conclusions about steroid-peptide interactions can be drawn, based on research with this amphibian. First, gonadal steroid hormones act to maintain the behavioral actions of AVT in both males and females. In Taricha, gonadectomy abolishes and steroid implants restore AVT-induced courtship in males and egg laying in females. Second, gonadal steroids maintain the behavioral actions of AVT, in part, by modulating AVT receptor numbers on target neurons. In Taricha males and females, gonadectomy reduces AVT receptor concentrations (but not binding affinity) in certain brain areas (amygdala pars lateralis) and not others. Third, the type of gonadal steroid determines whether AVT elicits male like or female-like reproductive behaviors. Ovariectomized Taricha females respond to AVT injections with egg-laying behaviors when implanted with estradiol and with male-like amplectic clasping when implanted with dihydrotestosterone. Fourth, the masculinization of AVT-induced behaviors in females most likely reflects site-specific actions of androgens on AVT-synthesizing neurons. In Taricha, AVTir concentrations in the optic tectum are sexually dimorphic (higher in males than females) and reach peak levels in males during the breeding season. Fifth, AVT content in specific brain areas increase as a function of performing the behaviors. In Taricha, AVTir concentrations in DPOA, CSF, and ventral infundibulum are higher in males that exhibit courtship behaviors than in males that do not. These conclusions illustrate how steroid-peptide interactions in the control of behaviors entail multiple neuroanatomical sites and neurochemical actions. PMID- 1626828 TI - Oxytocin involvement in male and female sexual behavior. PMID- 1626829 TI - Oxytocin and social bonding. AB - The prairie vole is an excellent model for examining the neurobiology of social attachment, and in particular of pair-bond formation. In female prairie voles either sexual interactions or oxytocin infusions can hasten the formation of a partner preference. These results implicate oxytocin in the formation of adult heterosexual social bonds. In conjunction with work on other social systems described in this volume, these findings also support the suggestions of Klopfer and Newton that oxytocin may be important in coordinating mammalian social interactions with other critical reproductive events such as birth, lactation, and sexual behavior. PMID- 1626830 TI - Role of vasopressin in aggressive and dominant/subordinate behaviors. PMID- 1626831 TI - Vasopressin and the regulation of hamster social behavior. PMID- 1626832 TI - Oxytocin effects on emotional processes: separation distress, social bonding, and relationships to psychiatric disorders. PMID- 1626833 TI - Oxytocinergic neuronal systems during mating, pregnancy, parturition, and lactation. PMID- 1626834 TI - The regulation of oxytocin mRNA levels in the medial preoptic area. Relationship to maternal behavior in the rat. PMID- 1626835 TI - Neurotransmitter and neurohormonal regulation of oxytocin secretion in lactation. PMID- 1626836 TI - Push-pull perfusion and microdialysis studies of central oxytocin and vasopressin release in freely moving rats during pregnancy, parturition, and lactation. PMID- 1626837 TI - In situ hybridization for showing hormone effects on oxytocin mRNA in specific populations of hypothalamic neurons and their possible participation in multiplicative hormonal responses. PMID- 1626838 TI - Gonadal steroid modulation of vasopressin pathways. PMID- 1626840 TI - Ricin-cytotoxin conjugate administration reveals a physiologically relevant role for oxytocin in the control of gonadotropin secretion. PMID- 1626839 TI - Pituitary portal plasma levels of oxytocin during the estrous cycle, lactation, and hyperprolactinemia. AB - The median eminence receives fibers from both parvocellular and magnocellular OT neurons in the hypothalamus. The OT neuronal terminal in the median eminence is secretory and is the major source of the neuropeptide in the blood of pituitary portal vessels. The OT secretion into pituitary portal plasma increases by ovarian steroids, PRL, and the suckling stimulus. The OT secretion into the blood of pituitary portal vessels changes in parallel with the altered secretion of PRL from the pituitary. Because of correlative association between pituitary portal plasma OT and systemic plasma PRL and much abundant evidence for a direct stimulatory action of OT on PRL release, we propose that the pituitary portal vascular system serves as the window for the central OT neurotransmission to the pituitary lactotropes. PMID- 1626841 TI - Preventing suckling-induced release of oxytocin does not inhibit maternal aggression in lactating rats. PMID- 1626842 TI - Oxytocin messenger RNA levels in hypothalamic, paraventricular, and supraoptic nuclei during pregnancy and lactation in rats. Evidence for regulation by afferent stimuli from the offspring. PMID- 1626843 TI - Analysis of oxytocin release by microdialysis and interactions with progesterone. PMID- 1626844 TI - Physiological significance and interactions between oxytocin and central neuropeptide and monoamine neurotransmitters in the regulation of the preovulatory secretion of luteinizing hormone. PMID- 1626845 TI - The effects of hypogastric and pelvic neurectomy on oxytocin-induced facilitation of receptivity. PMID- 1626846 TI - Social and environmental determinants of centrally administered oxytocin effects on male squirrel monkey behavior. PMID- 1626847 TI - Oxytocin in the amygdala facilitates maternal aggression. PMID- 1626848 TI - Vasopressin and the individual differentiation in aggression in male house mice. PMID- 1626849 TI - Opposite effects of central amygdaloid vasopressin and oxytocin on the regulation of conditioned stress responses in male rats. PMID- 1626850 TI - Expression of exogenous vasopressin mRNA by magno-cellular neurons of the supraoptic and paraventricular nuclei in Brattleboro rats. PMID- 1626851 TI - Afferent projections of the hamster periaqueductal gray. A neural site where vasopressin can stimulate flank marking. PMID- 1626852 TI - Existence of a sexual dimorphism in vasopressin binding in the area of the ventromedial nucleus of the hypothalamus in hamsters. PMID- 1626853 TI - Oxytocin and related peptides elicit contractions of prostate and seminal vesicle. PMID- 1626854 TI - The oxytocin secretory response to dopamine receptor agonists in male and female monkeys. PMID- 1626855 TI - The quantitative effect of oxytocin (Pitocin) on human milk yield. PMID- 1626856 TI - The relation of the milk-ejection reflex to the ability to breast feed. PMID- 1626857 TI - Partner preference development in female prairie voles is facilitated by mating or the central infusion of oxytocin. AB - Results of these experiments indicate that females given at least 24 hours of cohabitation with a male develop a social preference for the familiar partner versus a stranger. Mating is not essential for the development of partner preferences, but clearly facilitates the onset of preferences. Females given six hours of cohabitation showed partner preferences only if they mated with the partner during cohabitation (Experiment 2) or if they received oxytocin (Experiment 3). Females that continued to mate during preference tests (Experiment 2, n = 4) mated exclusively with the partner. Oxytocin infusions, even in the absence of mating or estrogen priming, facilitated the development of partner preferences. PMID- 1626859 TI - Speculations concerning the physiological significance of central oxytocin in maternal behavior. PMID- 1626858 TI - Oxytocin activation of maternal behavior in the rat. PMID- 1626860 TI - The role of biotechnology in tropical diseases. PMID- 1626861 TI - Immunization of cattle with an inactivated polyvalent vaccine against anaplasmosis and babesiosis. PMID- 1626862 TI - Evaluation of a DNA-based probe for the detection of cattle experimentally infected with Babesia bigemina. AB - A digoxigenin-labeled probe was used for hybridization to various preparations of Babesia bigemina-infected erythrocyte extracts. Dot blot hybridization and immunological detection of DNA hybrids revealed that the probe was specific for B. bigemina DNA because it did not hybridize to the DNA of B. bovis, a closely related species. Studies of sensitivity showed that the probe would bind to as little as 1 ng of B. bigemina DNA, but not to 1 microgram of the B. bovis DNA. The probe reacted with equal intensity against seven B. bigemina isolates from different geographic areas. The lowest percentage of B. bigemina-infected erythrocytes detected was 0.001%, a level of parasitemia not usually detected with the light microscope. Six intact, mixed-breed steers, approximately 3 years old, were inoculated with a blood stabilate containing B. bigemina-infected erythrocytes. Blood samples collected from day -1 to day 86 postinoculation (PI) and prepared for DNA extraction were analyzed in a dot blot hybridization assay using a nonradioactive DNA probe. Hybridization reaction (HR) signals were compared to results obtained by light microscopy (LM) examination of Giemsa stained blood smears and to antibody titers of serum samples assayed with the complement fixation test (CFT) and indirect fluorescent antibody test (IFAT). Four of six inoculated steers became infected with B. bigemina as assessed by LM. The parasitemias were low (less than 0.01-0.05) at day 10 PI. Only three steers were serologically positive by CFT (titer 1:40-1:160) and IFAT (1:1280). All four infected steers had positive HR signals in the dot blot assay. The HR signals were observed from day 10 to day 77 PI and were usually correlated with the presence of parasites in blood as observed by LM. The HR signals varied in intensity for different blood samples from the experimental animals and with day of blood sample collection. Although the signal intensity did not correlate with the parasitemia level estimated by LM, the nucleic acid hybridization assay was more sensitive than LM, CFT, or IFAT for the detection of B. bigemina-infected cattle. PMID- 1626863 TI - Immunophenotypic characterization of owl monkey peripheral blood mononuclear cells. AB - A two-phase study was initiated to delineate the peripheral blood lymphocyte populations present in owl monkeys and to correlate those populations with immune response and parasitism during malaria infection. The goal of phase I of the study was to elucidate a monoclonal antibody panel that could be used to characterize peripheral blood mononuclear cell (PBMC) populations with flow cytometric techniques. Forty-two monoclonal antibodies (reported to be reactive with human and macaque lymphocyte antigens) were screened for activity to owl monkey PBMC. Eleven monoclonals were found to react: anti-H42A (MHC Class II DP like); anti-TH14B (MHC Class II DR-like); and anti-TH81A5 (MHC Class II DQ-like); anti-H58A (MHC Class I); anti-DH59B (granulocyte and monocyte); anti-B1 (B cell); anti-T4 (CD4); anti-Leu3a (CD4); anti-Leu11a (CD16); anti-60.3 (CD18); and anti OKM1 (NK and monocyte). In a preliminary retrospective study correlating antibody titers, parasitemia values, and MHC Class I and Class II marker profiles on PBMC to test antigens used in malaria vaccine trials, a significant negative association was observed between cells bearing MHC Class II molecules and the other elements of the comparison. In summary, an appropriate panel of monoclonal antibodies has been identified for characterizing PBMC in owl monkeys, and preliminary studies indicate a possible association between clinical outcome and expressed phenotypic PBMC markers. PMID- 1626864 TI - Leishmaniasis in the Caribbean Islands. A review. AB - A review is presented of the current knowledge relating to leishmaniasis in the West Indies. The only country where an autochthonous focus of cutaneous leishmaniasis has been discovered within the last 20 years is the Dominican Republic. Most of the cases are of the diffuse clinical type, which tend to be anergic to the Montenegro skin test, but subclinical or mild cases are apparently common. The responsible agent is a new species of Leishmania and the suspected vector is Lutzomyia cristophei, the only anthropophilic sandfly on the island; the black rat could be a wild reservoir for the parasite. Sporadic indigenous cases have also been reported in Martinique and in Trinidad. On the latter island, no new cases have been found in the last 60 years, and only an enzootic cycle between rodents and marsupials and Lu. flaviscutellata exists there at present; the responsible parasite in this cycle is L. amazonensis or a closely related species. An apparently indigenous case of visceral leishmaniasis has been reported in Guadeloupe but new studies are needed to confirm if this form of the disease is endemic on the island. The sandfly fauna in some of the larger islands is discussed in relation to the existence of possible vectors and the establishment of the disease. In the case of Haiti, there is no reason for human leishmaniasis not to be present as it is in the neighboring Dominican Republic. In Trinidad, the conditions are present for leishmaniasis to become a true zoonosis at any time, produced by L. amazonensis. In Cuba, conditions seem to be favorable for the introduction of cutaneous leishmaniasis in the near future. No predictions can be made at this time for other islands because of lack of information about the existence of the factors required. PMID- 1626865 TI - A redescription of schizogony of Cytauxzoon felis in the domestic cat. AB - Cytauxzoon felis is a protozoan parasite that is transmitted by Dermacentor variabilis ticks and causes a uniformly fatal disease in domestic cats. In order to study schizogony and merozoite formation, D. variabilis nymphs were allowed to feed on domestic cats experimentally infected with C. felis, after which the molted adult ticks were fed on susceptible cats. Lung and liver tissues were collected from the cats during clinical cytauxzoonosis and were fixed for light and transmission electron microscopy. Some stages of parasite development were evident with light microscopy, but specific events associated with merogony could be documented only with electron microscopy. Schizogony was observed in endothelial macrophages of all tissues examined. The parasite appeared first as a multinucleated syncytium in which nuclear proliferation was evident. As the parasite syncytium developed, it became an increasingly elaborate labyrinth with extensive branches that were interconnected by thin processes of parasite cytoplasm. Organelles, including mitochondria and rhoptries, became apparent. Merozoite formation seemed to occur by rapid sequential fission along the margins of the multinucleated sporont in the cytoplasm of the host cell. As the sporont became smaller, merozoites were produced in a rosette-like configuration from the remaining parasite mass. Merozoites entered erythrocytes directly by endocytosis, without apparent injury to these cells. The sequence of events associated with merozoite formation in Cytauxzoon felis described herein differs from the previous description for this species and appears to be analogous to that described for the genus Theileria. PMID- 1626866 TI - Leptospira serology in small ruminants on St. Croix, U.S. Virgin Islands. AB - A serological survey of 16 serovars of Leptospira interrogans, previously reported in tropical small ruminants, was undertaken to determine the serovars involved and the prevalence of these antibodies in sheep and goats on St. Croix, U. S. Virgin Islands (USVI). Seven of eight goat herds (108 animals) had at least two seropositive animals in each herd with an individual animal seroprevalence of 26%. The 53 sheep tested (one flock only) showed a 32% seroprevalence. Antibodies against seven serovars were detected in goats (autumnalis, ballum, bataviae, bratislava, canicola, icterohemorrhagiae, and pyrogenes). In addition, hardjo antibodies were detected in sheep. Serovar autumnalis accounted for about 30% of seropositive animals in each species. Many animals showed titers against more than one serovar. The number of seropositive animals suggests Leptospira may be a factor in the health of small ruminants on St. Croix. PMID- 1626867 TI - Serological survey for Lyme disease in domestic dogs and white-tailed deer from Oklahoma. AB - Sera from 223 randomly selected dogs and 489 white-tailed deer (Odocoileus virginianus) were tested for antibodies to Borrelia burgdorferi using an indirect kinetic ELISA. Dog samples were obtained in 1989 whereas deer samples were obtained between 1975 and 1990. Ten known negatives and two known positives from each group were run on each plate as controls. Samples showing mean mOD values above the mean of negatives + 3 SD were considered positive. Twenty-six dog (11.7%) and 22 deer (4.5%) samples were positive. Deer reactors were first detected among 1978 samples. Reactive deer were from central and eastern Oklahoma whereas reactive dogs were mostly from central Oklahoma. Confirmed human cases between 1986 and 1989 were distributed throughout the state, thus showing no correlation with either deer or dog results. PMID- 1626868 TI - Production of anti-idiotypic antibodies as potential immunoreagents for the serological diagnosis of bovine cysticercosis. AB - Although serological assays have been developed for cysticercosis, difficulties remain in isolating antigens from cross-reacting components and in obtaining reliable sources of parasite material for purification. The object of this study was to demonstrate the feasibility of using anti-idiotypic antibodies as alternative immunoreagents for the serological diagnosis of bovine cysticercosis. A fraction of Taenia hydatigena cyst fluid (ThFAS) had previously been used as a diagnostic antigen for Taenia saginata cysticercosis. Rabbits and mice were inoculated with ThFAS to produce either polyclonal or monoclonal antibodies (idiotypes), respectively. Idiotypes were purified by preparative protein A column, then inoculated into other rabbits to produce anti-idiotypes. The presence of anti-idiotypes in hyperimmune serum was demonstrated by competitive inhibition ELISA. Then anti-idiotypes were purified and used as coating antigen in a plate ELISA; results were compared to those using ThFAS as coating antigen. Anti-idiotypes yielded results comparable to those obtained with the native antigen and thus can be used as synthetic antigens for diagnostic purposes. PMID- 1626869 TI - Amyloidosis, hemochromatosis, and atherosclerosis in a roseate flamingo (Phoenicopterus ruber). AB - An aged male roseate flamingo, in a private collection in the British Virgin Islands, was found acutely "down." After four days of supportive therapy, the flamingo succumbed. At necropsy gross lesions included emaciation; collapsed and thickened, yellow abdominal air sac; dark red liver, partially covered by friable yellow material; and a raised, intimal plaque in the aorta near the iliac trifurcation. Histologic examination revealed severe, diffuse, pyogranulomatous air sacculitis with associated locally extensive pleuroperitonitis/perihepatitis. Pansystemic, predominantly periarteriolar distribution of amyloid deposition was evident, as was massive intrahepatocellular accumulation of iron pigment (hemachromatosis/hemosiderosis). A locally extensive, nonobstructive, fibroatheromatous plaque was present in the distal aorta. Amyloidosis, hemochromatosis/hemosiderosis, and atherosclerosis have been recognized in Phoenicopteriformes and other marine or aquatic birds. Their pathogenesis and pathogenicity remain a matter of debate. PMID- 1626870 TI - Hematological study of water buffalo (Bubalus bubalis) during theileriosis (Theileria annulata). PMID- 1626871 TI - Wasting disease associated with cutaneous and renal nematodes, in commercially obtained Xenopus laevis. AB - Xenopus laevis, the South African clawed frog or toad, is a member of the family Pipidae. Now in high demand for research purposes, they are available commercially. Its reported lifespan is up to fifteen years. Investigators and caretakers are frustrated when commercially obtained, young frogs (four years or younger), not subjected to any studies, "waste" and die. The wasting syndrome is characterized by anorexia, color change, and "flaky skin." Often the first sign of this syndrome is the presence of large fragments of "flakes" of desquamated epithelium in the water. At necropsy, these frogs are thin and have rough skin instead of smooth slimy skin. Histologic examination reveals tortuous intraepithelial cavities or tunnels that contain nematodes, and associated mild to moderate granulomatous inflammation. Nematodes are also found in the kidneys of some of these frogs, usually in Bowman's space, wrapped around the glomerulus. The cutaneous capillarid nematode is identified as Pseudocapillaroides xenopi. Successful treatment with ivermectin and thiabendizole has been reported. The renal glomerular nematode has not been identified. PMID- 1626872 TI - An epizootic of Tanaisia bragai in a captive population of Puerto Rican plain pigeon (Columba inornata wetmorei). PMID- 1626873 TI - Hemodynamics of heartworm infection. AB - To determine the hemodynamic responsiveness of dogs testing positive for heartworms (direct blood smear), we compared the response of control and heartworm-infected animals to stellate stimulation (SS). Using the anesthetized, open-chest model, twenty dogs (10 control and 10 heartworm-positive) were instrumented to measure left ventricular pressure (LVP), arterial pressure (AP), and coronary flow velocity (CFV) of the left circumflex coronary artery. CFV was converted to flow per gram tissue (CBFG) by weighing the perfusion area of the circumflex artery. The average wet weight of the worm mass infecting the dogs was 1.0 +/- 0.1 g, which represented an average of 5% of the right ventricular free wall weight. Overall heart size and right ventricular weights were greater in the heartworm-positive animals, as well as heart weight to body weight ratios. Prior to SS, LVP was the same for both groups. However, dP/dt and CBFG were 21% and 19% lower, respectively, in the heartworm-positive animals. Stellate stimulation sufficient to produce a 30-mmHg rise in AP led to 25%, 13%, and 40% increases in LVP, dP/dt, and CBFG, respectively, in the control animals. Increases of 22%, 10%, and 52% in the same parameters were observed in the heartworm-positive animals. Although control dP/dt and CBFG in the heartworm-positive animals were lower than in the heartworm-negative animals, heartworm infection at this level did not hinder myocardial responsiveness to SS. PMID- 1626874 TI - A method for the recovery of infective larvae from Toxocara canis eggs for collection of larval secretory/excretory products. PMID- 1626875 TI - Venezuelan equine encephalomyelitis and African horse sickness. Current status and review. AB - The arthropod-borne virus (arbovirus) diseases of livestock have worldwide impact. The prevention of an introduction of an exotic disease and the control of one subsequent to an introduction will require the attention, cooperation, and support of the livestock industry, regulatory agencies, and researchers. The most effective protection of our livestock industries is to prevent the introduction of an exotic disease agent. This implies complete restriction of animal imports and exports. However, "zero risk" is an unacceptable option in today's world of internationally integrated and interdependent agriculture. Scientifically sound and factually based regulatory decisions must be combined with continued vigilance and preparedness, as well as appropriately directed surveillance and research, to protect the world agricultural marketplace. Two exotic arbovirus diseases that are of current concern to the livestock industries and regulatory officials of the North American and Caribbean Basin countries are VEE and AHS. Devastating epizootics of VEE in equines have occurred frequently in the Western Hemisphere, but no recent epizootic activity has been documented. Naturally occurring foci of sylvatic, equine nonpathogenic VEE virus subtypes, however, do exist in the tropical countries of the hemisphere. The relationship of these sylvatic virus foci to the origin of equine virulent epizootic VEE virus subtypes is unknown. AHS epizootics had been confined to Africa, the Middle East, and the Indian subcontinent until recent outbreaks in 1966 and 1987-1990 in Spain. With the recurrence of AHS in Spain for the past four years, concern about the possible introduction into potential vector species and equines in the Western Hemisphere has increased. This review addresses the current VEE and AHS virus activity and the potential for outbreaks in the Western Hemisphere. PMID- 1626876 TI - A review of African horse sickness with emphasis on selected vaccines. PMID- 1626877 TI - Rift Valley fever: present status and risk to the Western Hemisphere. PMID- 1626878 TI - Experiences with African swine fever in Haiti. PMID- 1626880 TI - Recent advances in the biology of Anaplasma spp. in Dermacentor andersoni ticks. PMID- 1626879 TI - Macroepidemiology of the HIVs-AIDS (HAIDS) pandemic. Insufficiently considered zoological and geopolitical aspects. AB - The human immunodeficiency viruses (HIVs)-acquired immunodeficiency syndrome (AIDS) or HAIDS pandemic originated from lentiviruses of nonhuman primates (thus qualifying as a zoonosis) that moved into humans in Africa. The HAIDS patients eventually die of opportunistic infections, all potentially zoonotic. The HAIDS infection remained parochial, first endemically and then epidemically, until the African urbanization that occurred in each of the countries postindependence. The latter included wars and the massive movement of soldiers (virologically naive) from the American continent to Africa and back. The HAIDS viral ecology coincided with African swine fever (ASF) in the Americas. Haiti became the focal point for both infections. Some infected Haitians also became, together with some infected drug addicts in the United States, a source of contaminated human blood for transfusions and production of plasma derivatives. PMID- 1626881 TI - Treatment strategies for human arboviral infections applicable to veterinary medicine. PMID- 1626882 TI - The role of Amblyomma variegatum in the transmission of heartwater with special reference to Guadeloupe. AB - Heartwater has been diagnosed in Guadeloupe, Marie-Galante, and Antigua; it induces important losses among goats and European or cross-bred cattle when local zebu creole are highly resistant to infection. Amblyomma variegatum is the vector of the disease in the Caribbean. The tick strain of Martinique, occurring in that island that has apparently been disease-free since 1948, has not lost its ability to experimentally transmit the disease. In Guadeloupe 97% of nymphs and nearly 100% of adults feed on cattle and goats. Some immature ticks (4.5%) feed on wildlife, including birds that may be involved in the spread of infected ticks. Only 1 to 4% of adult ticks are infected and only a proportion of infected ticks are really infective: 53%, 9%, and 50% of nymphs, males, and females, respectively. Nymphs play the major role in the transmission: they are more numerous than adults and engorge faster. Infected ticks have the same maximum longevity as noninfected ticks, that is, 18 months for nymphs and nearly 23 months for adults. Cowdria is not transmitted immediately after tick fixation but after a delay of 2-3 days for nymphs and 4 days for adults. The disease is more often fatal when transmitted by tick biting rather than by needle transmission. The daily infection rate that summarizes all the parameters is very low (0.14% and 0.20% for goats and cattle, respectively), resulting in an unstable epidemiological situation. The transmission of Cowdria by A. variegatum in Guadeloupe shows significant differences compared with the transmission by A. hebraeum in Africa. PMID- 1626883 TI - Chemotherapeutic prevention of complications caused by vaccinia virus-vectored immunogen. AB - Vaccinia virus strains and constructs differ greatly in the number of PFUs required to produce tail lesions in the vaccinia virus mouse model. The pathogenesis of lesion formation appeared to involve virus spread from an initial focus in specific cells surrounding hair follicles to other concentrated areas of the dermis and finally, at the time of lesion development, to the epidermis. Antivirals that suppressed tail lesions, to a greater or lesser degree, included ara A, ribavirin, rifampicin, adenosine N'-oxide, and selected analogues. Immunomodulators, including ampligen and recombinant interferon, suppressed lesions at very low doses. Spread of virus infection from the dermis to the epidermis was inhibited as determined by immunofluorescence. These studies in the tail lesion model have suggested drugs that could be tested further in primate models of vaccinia virus infection. In addition, these studies provide additional data on a model that may be a useful adjunct in safety testing of recombinant vaccinia virus vaccines. PMID- 1626884 TI - Mongoose rabies in the Caribbean. AB - Mongooses (Herpestes auropunctatus) have been introduced into most of the larger Caribbean islands, some notable exceptions being Dominica, Tobago, and Montserrat. Rabies in Caribbean mongooses is present in Puerto Rico, Cuba, the Dominican Republic (and presumably Haiti), and Grenada. Bat rabies is known on Cuba, Grenada, and Trinidad, although mongooses found on Trinidad are free of the disease. None of the other islands is known to have rabies, although it could be present in sequestered bat populations. All reported case numbers of mongoose rabies in the Caribbean are underestimates, and available information is at best incomplete and at times fragmentary. Nevertheless, data are presented from the four affected islands. Mongoose reduction campaigns have been undertaken on Cuba and Grenada. In Cuba strychnine sulfate inoculated into labeled eggs is used, whereas in Grenada sodium fluoroacetate (1080) has been used in boiled cowhide baits. Mongoose poisoning is unsatisfactory and ineffective in the long-term. Because many mongooses naturally exposed to rabies virus develop serum neutralizing antibodies and are considered to be immunized, possibly for life, vaccination in the wild has been under consideration since the mid-1970s. Early attempts to produce a pill coated with ERA vaccine for enteric absorption in mongooses were not very successful, but new modified vaccines and recombinant techniques hold considerable promise. PMID- 1626885 TI - The role of the veterinarian in hurricanes and other natural disasters. AB - Hurricanes create a multiplicity of complicated problems and hazards ranging from outbreaks of infectious disease to animal control problems precipitated by destruction of property. A multidisciplinary response is required to solve such problems. The pool of knowledge derived from various professionals interacting with multiple levels of government agencies (federal, state, and local) will provide the expertise needed. Because the veterinarian is trained to deal with disease involving populations of animals (e.g., herds or flocks) as well as individuals, and because of his/her intensive clinical training, the veterinarian is uniquely qualified to deal with the disaster situation. The veterinarian possesses extensive knowledge in disease and disease processes and has the capability of disease and injury management in affected populations, which qualifies him/her for an essential role, with unlimited potential as a member of any disaster relief team. There is considerable potential for veterinarians to play a role in responding to natural disasters. The areas of disease control, animal care, animal control, protection of the food supply, disinfection/sterilization, and planning are all areas where veterinarians can take an active part. Inclusion of the veterinarian in the process of planning for and responding to natural disasters will yield significant public health benefits. PMID- 1626886 TI - A new food safety strategy for tropical America. PMID- 1626887 TI - The Caribbean Animal and Plant Information Network. AB - The Inter-American Institute for Cooperation on Agriculture (IICA) is presently implementing a four-year project in the Caribbean region to establish a regional information network on animal and plant health--the Caribbean Animal and Plant Health Information Network (CARAPHIN). CARAPHIN's immediate goal is to give the participating countries the technical capability to process and analyze the phyto and zoo-sanitary information that they generate, share this information within the region, and use it as an effective instrument for decision making for agricultural development and trade. Sharing of information is further facilitated through the periodic regional and hemispheric meetings organized by IICA, by the Inter-American Animal Health Commission, and by the Technical Advisory Committee on Plant Protection. The Veterinary and Plant Protection Services of the region have expressed interest in the continuation of CARAPHIN as a permanent mechanism for agricultural health information management in the Caribbean. This motivated IICA to seek financing for a second phase of CARAPHIN, which will be executed from 1992 through 1996. Phase II of the project will seek to ensure the continuing application of the techniques and methodologies acquired by the agricultural health services of the different countries, and the functioning of the disease/pest information systems at the regional level. This will be achieved through technical assistance, continuing education, publications, provision of useful databases, and transfer of the project to a regional institution. PMID- 1626888 TI - Problems of developing a self-financing veterinary diagnostic laboratory service in southern Peru. PMID- 1626889 TI - Use of LANDSAT MSS imagery and soil type in a geographic information system to assess site-specific risk of fascioliasis on Red River Basin farms in Louisiana. AB - A geographic information system (GIS) was constructed in an ERDAS environment using maps of soil types from the USDA Soil Conservation Service, LANDSAT satellite multispectral scanner data (MSS), boundaries for 25 study farms, and slope and hydrologic features shown in a two-quadrangle (USGS, 7.5') area in the Red River Basin near Alexandria, Louisiana. Fecal sedimentation examinations were done in the fall of 1989, spring of 1990, and fall and winter of 1990-1991 on 10 16 random samples per herd. Fecal egg shedding rates for F. hepatica ranged from 10-100% prevalence and 0.3-21.7 eggs per two grams of feces (EP2G). For Paramphistomum spp., a rumen fluke also transmitted by F. bulimoides but not affected by flukicides, egg shedding rates ranged from 10-91% prevalence and 0.1 42.8 EP2G. Soil types present ranged from sandy loams to hydric, occasionally flooded clays. Herd Paramphistomum spp. egg shedding rates increased with the proportion of hydric clays present, adjusted for slope and major hydrologic features. F. hepatica infection intensity followed a similar trend, but were complicated by differing treatment practices. Results suggest that earth observation satellite data and soil maps can be used, with an existing climate forecast based on the Thornthwaite water budget, to develop a second generation model that accounts for both regional climate variation and site-specific differences in fascioliasis risk based on soils prone to snail habitat. PMID- 1626890 TI - Economic benefits of controlling internal and external parasites in South American camelids. AB - A trial was carried out in alpacas (Lama pacos) and llamas (Lama glama) to determine the economic benefits of controlling both external and internal parasites by the use of ivermectin ("Ivomec," Merck Sharp & Dohme). After four months the treated male alpacas gained on average 3.1 kg more than the untreated males, and their fleece weighed 0.36 kg more. The treated female alpacas gained 1.9 kg more than the controls, but their fleece weighed 0.03 kg less. This treatment gave a net financial benefit to the farmer of U.S. $3.54 for each of his male alpacas and U.S. $1.36 for each of his female alpacas. The results for the llamas were not significant because there was great variation in the weight gains (and losses). Because the value of llama fleece is less, the economic benefits were also less. PMID- 1626891 TI - Biology and transmission of Babesia bigemina in Boophilus microplus. PMID- 1626892 TI - Epizootiology of Lyme disease and methods of cultivating Borrelia burgdorferi. AB - Lyme disease is prevalent over vast areas of land in the northern hemisphere. The etiologic agent is a spirochete, Borrelia burgdorferi, that is transmitted by Ixodes ticks. At least five species of anthropophilic ticks are competent vectors, and the causative agent or closely related species have been detected in 20 wild or domestic mammals and eight birds. The ability to isolate and culture B. burgdorferi from humans, ticks, and wildlife has significantly contributed to our understanding of the epizootiology of Lyme disease. Specific procedures for isolating borreliae from ticks and rodents in Barbour-Stoenner-Kelly medium are described. The authors have preserved in liquid nitrogen more than 500 isolates from ticks, wildlife, and a human. PMID- 1626893 TI - Impact of zoonoses in tropical America. PMID- 1626894 TI - Eradication of Boophilus microplus (Acari: Ixodidae) in Puerto Rico. AB - The ongoing cooperative effort between the United States Department of Agriculture, Animal and Plant Health Inspection Service and the Puerto Rico Department of Agriculture to eradicate the southern cattle tick, Boophilus microplus (Canestrini), is reviewed. Epidemiological and biological aspects of the tick that influence efficient control and/or eradication in Puerto Rico are discussed. The differences between the current eradication methodology and that initially utilized by the program are emphasized. The status and possible future adaptations of the program, as well as its applicability to other areas in the Caribbean, are also addressed. PMID- 1626895 TI - Preliminary attempts to infect bovine erythrocytes in vitro with a tick-derived stage of Anaplasma marginale. PMID- 1626896 TI - Studies on the biology of Ixodes dammini in the upper midwest of the United States. AB - The seasonal activity pattern of Ixodes dammini was monitored in south-central Wisconsin in 1989 and 1990. Immature tick activity and abundance were assessed by small mammal trapping (732 Peromyscus leucopus examined) and supplemented with flagging. Tick survival and molting times were evaluated by maintaining ticks in environmental chambers at field sites. Results indicate the biology of I. dammini in the upper midwest is similar to that previously reported from the eastern United States. One notable difference was that seasonal larval activity appeared broader (late April through October) and peaked earlier (on 9 July 1989 mean was 7.7 larvae/mouse; on 9 June 1990 mean was 7.3 larvae/mouse). Nymphal activity on P. leucopus peaked in May of both years (mean = 2.5 in 1989; mean = 1.8 in 1990). Bloodfed females placed in the field in early May 1990 oviposited in early June, and larvae emerged by early August. All bloodfed stages successfully overwintered at field sites. PMID- 1626897 TI - Vaccines against coxiellosis and Q fever. Development of a chloroform:methanol residue subunit of phase I Coxiella burnetti for the immunization of animals. AB - We have demonstrated the safety, immunogenicity, and efficacy of the WC and CMR vaccines in guinea pigs. Vaccination of guinea pigs with either WC or CMR protects animals against challenge with virulent C. burnetii. A total of 2 micrograms of either WC or CMR vaccine was a significant priming dose. A total of 20 micrograms gave complete protection against lethal challenge. Detection of antibodies to phase II cells by microaglutination, after vaccination with either WC or CMR and before lethal challenge, correlated with the ability of guinea pigs to mount a protective immune response. The PD50 values for WC and CMR vaccines, administered as a single dose, were 0.3 and 1.4 micrograms per animal, respectively. In contrast, the PD50 values for the WC and CMR vaccines, administered as two doses, were 0.83 and 0.72 micrograms per animal, respectively. Although the PD50 values for the two vaccines are similar, the CMR vaccine is preferred over the WC vaccine because it induces significantly fewer adverse reactions, and repeat injections can be given. Unvaccinated guinea pigs do not clear infectious microorganisms after challenge infection. Vaccination before challenge infection reduces the infectious load of C. burnetti in the blood and in various organs of the animals. When vaccinated animals were challenge infected and treated with rifampicin, the microorganisms were not eliminated from various organs. However, the combination of vaccination, challenge, and rifampicin treatment is effective in reducing the number of infectious microorganisms in some of these sites. We have demonstrated the safety and immunogenicity of the CMR vaccine in sheep and goats. Animals that were seropositive for one or more antigens developed significant levels of antibodies to alternate antigens, but no adverse reactions were observed at the site of s.c. injection of the CMR vaccine. This demonstrates that seropositive animals can be successfully immunized with this vaccine. These results also indicate that a long term vaccination program using the CMR vaccine has the potential for producing animals with significant antibody titers to C. burnetii and perhaps lifelong immunity. The goal of a Q fever vaccination program is to produce immunized animals that are able to clear completely the infectious microorganisms. The appropriate vaccination schedule to render adult animals and their offspring "Q fever-free" should now be thoroughly investigated. PMID- 1626898 TI - Serge Alexander Korff (1906-1989). PMID- 1626899 TI - Are we ready for the year 2001? PMID- 1626900 TI - The surgery of otosclerosis. 1937. PMID- 1626901 TI - Tracheal agenesis. AB - Tracheal agenesis is a catastrophic congenital anomaly that invariably results in death. Forty-seven cases have been previously reported in the literature. We add five additional cases, including two type 1 cases, two type 2 cases, and one type 3 cases, based on Floyd's classification scheme. We describe the features of this unusual anomaly at the time of diagnosis. We discuss a rational approach to the management of this difficult problem on an emergent basis that allows for the maintenance of the infant's life until all of the implications of this fatal condition can be assessed. While we do not advocate reconstructive surgery for this anomaly, which has been universally fatal, we discuss the potential rearrangement of the anatomy, which may offer some hope in future cases. The concomitant congenital anomalies associated with these cases are reviewed, and autopsy specimens are presented for their anatomic interest. PMID- 1626902 TI - Videostroboscopy of human vocal fold paralysis. AB - Previous stroboscopic studies of human vocal cord paralysis have been infrequent and have lacked documentation of the site of lesion. In order to study human laryngeal paralysis, the recurrent and superior laryngeal nerves were infiltrated unilaterally with lidocaine hydrochloride in three human volunteers. Vagal paralysis was simulated by combined (superior and recurrent) infiltration in one volunteer. Additionally, 20 patients with untreated laryngeal paralysis were studied from the voice laboratory at UCLA. In addition to videostroboscopic analysis, photoglottography and electroglottography were performed and synchronized with the stroboscopic images. The most significant finding in stroboscopy of the paralyzed larynx was the asymmetry of traveling wave motion. The traveling wave on the normal vocal fold had a faster wave velocity that created a phase difference in the vibration of the two folds. The wave also traversed a greater distance along the vocal fold mucosa on the normal side. No patient or volunteer with untreated laryngeal paralysis had a symmetric traveling wave, either in superior or recurrent laryngeal nerve paralysis. Synchronization with glottography indicated that the differentiated electroglottographic waveform provides useful information about the timing of glottic opening and closure in states of asymmetric laryngeal vibration. Implications for future studies and for the diagnosis of laryngeal paralysis are discussed. PMID- 1626903 TI - Noninvasive technique for estimating subglottic pressure and laryngeal efficiency. AB - The clinical assessment of aerodynamic parameters is important in the physiology and pathophysiology of laryngeal function. Vocal efficiency is among these objective measurements and can be calculated from simultaneous recordings of subglottic pressure, airflow, and sound intensity. Modern techniques allow us to accurately determine sound intensity and airflow. However, methods to determine subglottic pressure are either invasive or laborious. We have evaluated a noninvasive, indirect method to determine subglottic pressure by using a technique based on the interruption of transglottic airflow during phonation. The correlation between the indirectly acquired subglottic pressure measured in the oral cavity by using this technique and the subglottic pressure obtained directly by translaryngeal puncture in human volunteers was highly significant in 35 trials (r = .92, p less than .01). This study describes a reliable technique for the noninvasive measurement of subglottic pressure, sound intensity, and airflow. PMID- 1626904 TI - Lidocaine effects on the laryngeal chemoreflex, mechanoreflex, and afferent electrical stimulation reflex. AB - The use of lidocaine hydrochloride as either a topical or intravenous agent has become a common practice for minimizing laryngospasm and the reflex cardiovascular effects resulting from upper airway manipulation. The efficacy and mechanism of action of lidocaine for this purpose remain unclear. We evaluated the effect of lidocaine on the laryngeal chemoreflex (LCR), mechanoreflex (LMR), and superior laryngeal nerve electrical stimulation adductor reflex (SLN-ESAR) in piglets. Cardiopulmonary responses were used to assess LCR and LMR. Latency following SLN stimulation was used to assess SLN-ESAR. Intravenous lidocaine hydrochloride at 3 mg/kg produced no suppression of the LCR, LMR, or latency (SLN ESAR onset latency before lidocaine 11.7 +/- 0.7 milliseconds, after lidocaine 12.2 +/- 0.5 milliseconds; peak latency before lidocaine 13.2 +/- 0.2 milliseconds, after lidocaine 13.4 +/- 0.4 milliseconds). Topically applied lidocaine at the same dose eliminated both LCR and LMR responses in all animals, with return of reflex responses 15 minutes after application. No effect on the SLN-ESAR was seen with application of topical lidocaine. This study supports topical lidocaine as a suppressant of laryngeal mucosal neuroreceptors without central neural reflex effects. Intravenous lidocaine did not affect peripheral neuroreceptors, nor did it significantly affect the latency of the SLN-ESAR neural reflex arc. Intravenous and topical lidocaine differ in mechanism of action and efficacy with regard to modulation of reflex effects induced by laryngeal stimulation. PMID- 1626905 TI - Meniere's syndrome inherited as an autosomal dominant trait. AB - Brown in 1941 reported on five families having two members with Meniere's syndrome. In 1949 she reported on three siblings (children of first cousins) and two identical twins bearing the syndrome. Bernstein in 1965 reported on seven families having two or more members afflicted by the symptoms. All these reports showed association between Meniere's syndrome and migraine headaches. None provided detailed pedigree studies in order to clarify the mode of genetic transmission. We report on a father, three daughters, and one son with typical Meniere's syndrome and paroxysmal headaches. The pedigree strongly suggests autosomal dominant transmission. After studying this family we have been paying close attention to family histories of Meniere's syndrome patients. It is not at all uncommon to hear about other members of the family with the syndrome, but it is difficult to document all of the cases for logistical reasons. PMID- 1626906 TI - Pediatric airway reconstruction at Great Ormond Street: a ten-year review. II. Revisional airway reconstruction. AB - One hundred eight consecutive patients with pediatric laryngotracheal stenosis requiring airway reconstruction over a 10-year period were reviewed. Thirty-two patients required revisional airway reconstruction in an attempt to achieve decannulation. Patients underwent from one to four revisional airway reconstructions, most often laryngotracheal reconstruction with costal cartilage grafting. In the Cotton grading scheme of preoperative stenosis, those patients requiring revisional airway surgery tended to come from the more severely affected categories. Twenty-two patients of 32 (69%) achieved decannulation with revisional airway reconstruction. Thus, revisional airway reconstruction is indicated if the first attempt fails. PMID- 1626907 TI - Orbital complications of acute sinusitis: comparison of computed tomography scan and surgical findings. AB - The accuracy of computed tomography (CT) in distinguishing an abscess from cellulitis in children who present with orbital manifestations of paranasal sinus infection remains in question. In this 10-year retrospective study, CT results are compared with surgical findings in 19 patients with orbital complications who underwent surgical exploration within 24 hours of their CT scans. Fifteen of the 19 CT scan interpretations indicated abscesses that were verified intraoperatively. Two patients had negative surgical explorations despite CT interpretations predicting abscesses. An abscess was also surgically documented in 1 of 2 patients whose preoperative scans indicated cellulitis alone. We conclude that the correlation between radiologic and operative findings in 16 of these 19 cases, although not absolute, does substantiate the use of CT scanning as a therapeutic guide in children presenting with orbital disease secondary to paranasal sinusitis. PMID- 1626908 TI - Planum semilunatum of the rat: new light and electron microscopy observations. AB - Planum semilunatum (PSL) cells of the rat ampullae were studied by light, transmission, and scanning electron microscopy. The observed ultrastructure of rat PSL cells was similar to that described in other species, but is in disagreement with earlier reports of rat PSL cells, most probably because of previous divergent definitions of the PSL. Regions of PSL cells were easily distinguished from other nonsensory epithelia at the lateral ends of the crista ampullaris. The PSL region consisted of irregular-shaped columnar to cuboidal pentagonal or hexagonal cells that interdigitated with one another by lateral membrane infoldings. In the PSL region the subepithelial reticular layer appeared thickened and formed wartlike impressions in the basal surface of the PSL cells. These morphological characteristics of the subepithelial reticular layer were unique to the PSL region in the ampulla and may reflect special adaptations of the PSL region to mechanical stress. Furthermore, the thick subepithelial reticular layer may have implications for transport across the PSL region. PMID- 1626909 TI - Effect of endotoxin on cultured chinchilla middle ear epithelium. AB - The effect of endotoxin on the growth and morphology of cultured chinchilla middle ear epithelium was examined. Within 24 hours of culture, cells maintained in medium containing endotoxin exhibited dose-dependent morphological changes. The highest concentration of endotoxin (100 mg) resulted in cell death. The growth curve of the cells in culture demonstrated a dose-dependent, significant increase in cell number when endotoxin was added to the medium. PMID- 1626910 TI - Vestibular pathophysiologic changes in experimental perilymphatic fistula. AB - An animal model of experimental perilymphatic fistula (EPLF) was developed in the guinea pig in order to study vestibular pathophysiology. In experimental animals, 4 microL of perilymph was suctioned from one cochlea via the round window membrane. Changes in vestibular function were as follows. 1) During the acute stage (5 hours postoperatively), spontaneous nystagmus directed toward the normal side was noted in 57.4% of the EPLF animals. This lasted less than 24 hours. 2) One week postoperatively, direction-fixed positional nystagmus toward the lesioned ear was present in 22.7% of the EPLF animals, especially when the lesioned ear was positioned inferiorly. 3) With the ice water caloric test, no response was present in 58.1% of the EPLF animals and an irregular response was found in 22.6% of them, 1 week postoperatively. These results tend to indicate that tests of vestibular function may differentiate between patients with Meniere's disease and those with perilymphatic fistula. Histologic findings indicate that a floating labyrinth is the cause of positional nystagmus and caloric irregularity. The absence of caloric responses was associated with collapse of the vestibular labyrinth. PMID- 1626911 TI - Cartilaginous tumor of the larynx. PMID- 1626912 TI - Calcification of internal auditory canal tumors. PMID- 1626913 TI - Choanal and angiomatous polyps of the sinonasal tract. AB - Choanal and angiomatous polyps can be distinguished from ordinary sinonasal polyps by either a distinctive clinical presentation (choanal) or the histopathologic appearance (angiomatous). Nearly all choanal polyps arise within paranasal sinuses, with the antrochoanal polyp the most common. The angiomatous polyp is most often a secondary change in a choanal polyp and can be mistaken for vascular neoplasms, eg, angiofibroma. PMID- 1626914 TI - Drug receptor assays: quo vadis? PMID- 1626915 TI - Insulin-like growth factor 1: a valid nutritional indicator during parenteral feeding of patients suffering an acute phase response. AB - Insulin-like growth factor 1 (IGF-1) is regulated by nutritional intake independently of growth hormone and may be a better nutritional indicator than the plasma proteins. This possibility was investigated in six malnourished inpatients, who suffered sepsis, surgical trauma, or both and who received total parenteral nutrition (TPN) for 10-35 days. Both plasma IGF-1 and pre-albumin showed (P less than 0.05) increases during TPN from baseline values of 0.042-0.42 U/mL (median, 0.11) and 59-156 mg/L (median, 108), respectively, to maxima of 0.19-1.12 U/mL (median, 0.63) and 140-363 mg/L (median, 203). Statistically significant (P less than 0.05) positive correlation occurred between nitrogen balance (range, -7.5 to +11.0 g/day) and IGF-1 or pre-albumin. Correlation between nitrogen balance and IGF-1 is preserved during the acute phase response to tissue injury when C-reactive protein (CRP) varies in the range 40-248 mg/L. Under these circumstances, the correlation between nitrogen balance and pre albumin is, in contrast, abolished. These results suggest that IGF-1 behaves as a valid index of nutritional adequacy during parenteral feeding whereas pre-albumin reflects mainly the acute phase response. PMID- 1626916 TI - Variation of sweat sodium and chloride with age in cystic fibrosis and normal populations: further investigations in equivocal cases. AB - Patients attending cystic fibrosis clinics had sweat sodium and chloride concentrations measured, were reassessed clinically and had DNA studies performed. Sweat test results were compared with a matched control population. In both populations sweat sodium increased with age up to 12 years, and did not change significantly thereafter. The age-related increase was significantly less in the cystic fibrosis group. Sweat chloride increased with age in normal, but not in cystic fibrosis children. After age 12 years there was no age-related change in the normal group, and a fall with age in the cystic fibrosis group. Sweat chloride provided the best discrimination between normal and cystic fibrosis populations and this was particularly important in older subjects. Combining sweat sodium and chloride results did not improve discrimination. Nine patients were identified with equivocal sweat chloride results. DNA studies showed six of these subjects were heterozygous for the delta F508 mutation in the cystic fibrosis gene. Clinical assessment did not always resolve cases with borderline sweat chloride results. PMID- 1626917 TI - Incomplete testicular feminization syndrome: studies of 17 beta-oestradiol binding activity and aromatase activity in cultured genital fibroblasts showing impaired dihydrotestosterone-binding. AB - Dihydrotestosterone (DHT) and 17 beta-oestradiol binding, and aromatase activity were measured in cultured genital skin fibroblasts from two siblings with the incomplete testicular feminization syndrome. Whole-cell and nuclear DHT binding in the cells from both patients were reduced to 80% and 60%, respectively of those in a normal male subject. The nuclear oestradiol binding was not impaired in the fibroblasts from the patients whose plasma oestradiol was normal or a little elevated. Although gonadectomy led to a decrease in plasma testosterone concentration, the concentration of testosterone-binding globulin showed no change suggesting no apparent effect on testosterone-binding globulin synthesis by testicular steroids. There was no significant difference in aromatase activity of the fibroblasts between the patients and the normal male subjects. The relatively increased oestrogen concentration in the syndrome might result from oestrogen production in testes, but is unlikely to be from peripheral tissues such as fibroblasts. This is the first report to examine oestradiol binding and aromatase activity in the cells from the incomplete testicular feminization associated with impaired DHT binding. These findings may give new insight into the pathogenesis of abnormal male sexual differentiation in the patients with testicular feminization syndrome. PMID- 1626918 TI - Serum urate, serum glucose and diabetes. AB - We have studied the relationship between serum glucose and urate in 260,699 men and 214,118 women from Sweden, and 140,084 men and 30,653 women from the UK. We found an increase in mean serum urate with increasing glucose concentrations up to 7.0 mmol/L in men and 9.0 mmol/L in women. Thereafter increasing glucose values were accompanied by a statistically significant decrease in urate concentrations. This fall was particularly marked in younger subjects. We believe this may have important implications for the free radical status of diabetics. PMID- 1626919 TI - Measurement of dopamine, HVA and HMMA in untimed urine samples: establishment of age-related reference data in children. AB - We describe assays for homovanillic acid, hydroxymethylmandelic acid and dopamine that have proven practical and reliable during 3 years of routine use. Homovanillic and hydroxymethylmandelic acids were measured as trimethyl silyl derivatives by capillary gas chromatography. Dilution of samples prior to extraction was found to be necessary to achieve consistent recoveries of these acidic metabolites. Dopamine was assayed by high pressure liquid chromatography with electrochemical detection using an optimized method of catecholamine isolation that involved both ion exchange and alumina extraction. Untimed urine samples were collected from 140 hospitalized children. Age related reference data for the excretion of all three metabolites are reported. We suggest certain precautions that should be observed when using untimed samples and relating the results to creatinine excretion. PMID- 1626920 TI - A method for the determination of sex hormone binding globulin using Concanavalin A-sepharose. AB - A binding assay for sex hormone binding globulin (SHBG) has been developed in which SHBG is saturated with tritiated dihydrotestosterone (DHT). Separation of bound and free DHT is achieved by using Concanavalin A-Sepharose as a solid phase matrix. The method is described and its performance, including linearity, imprecision and comparison with other methods, is assessed. The assay is simple and robust and is suitable for analysis of samples of plasma or serum for clinical or research use. PMID- 1626921 TI - Circulating levels of tartrate-resistant acid phosphatase in macrophage-activated lung disease. AB - Tartrate-resistant acid phosphatase (TrACP) is abundant in alveolar macrophages, suggesting that these cells might contribute to the activity of this isoenzyme in sera of patients with conditions characterized by activation of alveolar macrophages. TrACP was therefore measured in patients with pulmonary sarcoidosis and cryptogenic fibrosing alveolitis and compared with values in controls. Since osteoclasts are known to be the main source of TrACP in serum several indices of bone-turnover were also measured: serum bone-specific alkaline phosphatase and urine hydroxyproline:creatinine ratios. Patients with Paget's disease of bone constituted a reference group presenting increased bone turnover. TrACP was not significantly higher in the lung-disease groups than in controls, although there was a strong positive correlation with angiotensin-converting enzyme in pulmonary sarcoidosis. As expected, TrACP activity was elevated together with the other indices of bone turnover in Paget's disease. It is unlikely that TrACP from alveolar macrophages contributes significantly to serum acid phosphatase activity in lung disease. PMID- 1626922 TI - A reference preparation of human prostatic acid phosphatase: purification, characterization and field trials. AB - Acid phosphatase has been prepared in an apparently pure state by affinity chromatography from human prostatic tissue. When dissolved in an acidic albumin solution, lyophilized and stored at -20 degrees C for up to 2 years, no time dependent loss of catalytic activity was detectable in the reconstituted material. Accelerated degradation tests also predicted complete stability. A preliminary distribution of the lyophilized preparation to 143 laboratories confirmed its robustness and demonstrated its potential usefulness as a calibrant to unify the results of different methods of measuring acid phosphatase activity. PMID- 1626923 TI - Human serum and urine glycosaminoglycans in health and in patients with chronic renal failure. AB - Quantitation of uronic acid precipitable by cetylpyridinium chloride (CPC) and electrophoretic separation of glycosaminoglycans were performed on sera from patients with chronic renal failure and compared to normal controls. Serum CPC precipitable uronic acid (CpUA) levels in patients with renal failure were significantly higher (mean 13.7 mg/L, range 7.1-23.6 mg/L) than normal controls (mean 9.6 mg/L, range 5.1-13.9 mg/L) due to increased concentrations of low sulphated chondroitin sulphate. A positive correlation between serum CpUA and creatinine was found in renal failure patients. Urine CpUA excretion was raised in renal failure patients compared to normal controls with an increased excretion of chondroitin sulphate (Ch-S) of reduced electrophoretic mobility. Heparan sulphate (HS), a major glycosaminoglycan in normal urine, was absent from the urine of these patients. The possible origin of urine glycosaminoglycans and the role of the kidney in glycosaminoglycan metabolism are discussed. PMID- 1626924 TI - A method for quantitative measurement of mitochondrial creatine kinase in human skeletal muscle. AB - Defects in the mitochondrial energy generating system in patients with a mitochondrial myopathy are known to be localized in various enzyme complexes involved in energy production. Such a defect may exist at the level of mitochondrial creatine kinase (Mi-CK). On that account we have developed a method for measurement of the enzyme activity in human skeletal muscle biopsy material (greater than 10 mg). Interfering creatine kinase isoenzymes are removed by anion exchange and affinity chromatography. The activity of Mi-CK in reference skeletal muscle homogenates amounts to 240 +/- 88 mU/mg protein (30 +/- 8.0 mU/mg wet weight). PMID- 1626925 TI - Creatine kinase isoforms: investigation of inhibitors of in vitro degradation and establishment of a reference range. AB - The in vitro stability of creatine kinase isoforms was examined by separation with high voltage electrophoresis. The effect of inhibitors of carboxypeptidase was evaluated. Preservation of samples is essential to inhibit in vitro changes in isoform pattern. EDTA at a final concentration of 15 mmol/L is recommended. Using appropriately preserved samples, normal reference intervals for the MM isoforms have been established. PMID- 1626926 TI - Carbamylated haemoglobin in normal, diabetic and uraemic patients. AB - Carbamylated haemoglobin arises from the non-enzymic modification of haemoglobin monomers by isocyanate derived from the spontaneous dissociation of urea. We measured carbamylated haemoglobin by high performance liquid chromatography in healthy subjects, non-uraemic hospital patients, diabetics, and different groups of uraemic patients. Carbamylated haemoglobin levels were found to be raised in uraemic subjects, but were independent of age, sex, glycaemic state and haemodialysis procedure. There was no significant difference in carbamylated haemoglobin levels between two groups of patients having different modes of dialysis treatment, probably indicating a similar degree of uraemic exposure in these patients. PMID- 1626927 TI - Immunoblotting of transferrin in the identification of cerebrospinal fluid otorrhoea and rhinorrhoea. AB - Cerebrospinal rhinorrhoea is potentially serious due to the risk from infection. In patients presenting with a nasal discharge of clear fluid it is important to identify the nature of the fluid. Cerebrospinal fluid is readily identified by the presence of asialo-transferrin (tau protein). A method is presented for the identification of tau protein based upon agarose electrophoresis, followed by transfer onto cellulose nitrate membrane and immunochemical detection of transferrin. The method is reliable, sensitive and simple, and requires only basic electrophoresis apparatus. PMID- 1626928 TI - Achieving consensus on out-of-hours laboratory tests. AB - Many reports on guidelines for investigation describe either the guidelines themselves or their implementation. Implicitly these assume that there has been general agreement about the guidelines, whereas there may be uncertainty about the appropriateness of a particular investigation in a given situation. We report the use of a technique for developing guidelines which explicitly seeks to identify areas of agreement and disagreement, and focuses on the reasons that particular decisions were made and the causes of disagreement. PMID- 1626929 TI - Lead haem saturation method: a method for measuring red cell lead binding protein. PMID- 1626930 TI - Sample storage conditions for the assay of glyoxalase activities in whole blood samples. PMID- 1626931 TI - Effect of educational feedback on clinicians' requesting of cardiac enzymes. PMID- 1626932 TI - Effect of racial variation in serum creatine kinase on interpretation: a case report. PMID- 1626933 TI - Clinical and metabolic findings in a patient with phytosterolaemia. PMID- 1626934 TI - Pseudohyperphosphataemia in multiple myeloma. PMID- 1626935 TI - The incidence of asymptomatic hypothyroidism in new referrals to a hospital lipid clinic. PMID- 1626936 TI - [Complications and their management in intraarterial infusion chemotherapy]. AB - Complications and its management were evaluated in intraarterial infusion chemotherapy for 188 patients with advanced carcinoma of the digestive organs from 1975 to Sept. 1991. Subjects were divided into four groups: Group I was 62 patients in whom the tip of the catheter without knots was established in the abdominal aorta via celiac axis, Group II consisted of 72 patients with the tip of the catheter without knots in the common hepatic artery. Group III had 35 patients with the tip of the catheter with knots (Anthron catheter) in the common hepatic artery. Group IV was 19 patients with the tip of the anthron catheter connected to the Infuse A-Port in the common hepatic artery. The most frequent complications seen among Group I, II and III were caused by catheter thrombosis (11.3%) in Group I, spontaneous dislodgement of catheter (26.4%) in Group II and extravasation (20%) in Group III. By using 16 gauge Toray Anthron catheter with Heparin coating on its inner and outer surfaces, the number of complications in Group I and II was kept smaller. Extravasation, on the other hand, has been less frequently seen in Group III by establishing the tip of the catheter at the branching site of the gastroduodenal artery from the common hepatic artery. Complications in Group IV (19 patients) were noted only in 3 patients, i.e., extravasation, subcutaneous necrosis and subcutaneous abscess, respectively. Therefore, we concluded that Group IV showed the most favorable intraarterial infusion chemotherapy with the most infrequent complications. PMID- 1626937 TI - [The study on intravesical instillation of THP in the treatment of in-situ and superficial bladder cancers]. AB - The efficacy and safety of Pirarubicin (THP), administered by intravesical instillation, have been studied in recurrent multiple superficial bladder cancer patients and patients who tested positive by urine cytology but lacked protuberant legions (CIS). The average age and range of the 19 patients (M 15, F4) studied were 63.3 (37-84). Twelve patients had protuberant, multiple cancer and 7 patients had CIS. Sixteen of the cases were recurrent disease. Twenty mg THP, delufed in 40 ml of 5% glucose solution were instilled for 2 hours once or twice a week. Each patients received 8 treatments. One week after the last treatment, the therapeutic result was evaluated on the bases of cystoscopy and urine cytology. Before and after administration, CBC and biochemical blood tests were run. Nine of the 12 patients (75%) with multiple recurrent tumor and all the 7 patients with CIS showed complete response. The total outcome for CR was 84.2% in this study. Intravesical instillation with THP did not cause any serious side effects. PMID- 1626938 TI - [A phase I study on a weekly schedule of DWA2114R]. AB - A phase I study on a weekly schedule of DWA 2114R, a new platinum analogue, was conducted in 21 patients with various tumor types by clinical groups at 10 institutions. Nineteen of the 21 patients entered in this study were evaluable. The starting dose was 200 mg/m2 (1 n) administered intravenously for 1 hr and gradually escalated stepwise to 700 mg/m2 (3.5 n). The dose limiting factor (DLF) was leukocytopenia, especially neutropenia and maximum tolerated dose (MTD) was 700 mg/m2. The major clinical toxicity was gastrointestinal. Nephrotoxicity and hepatotoxicity were mild. Ototoxicity and cardiac failure did not emerge. Following administration of the drug, total platinum (Pt) showed a biphasic decay and AUC of total Pt was dependent on the dose. Excretion into urine 24 hr was between 42.6 and 100% of the administered platinum. The recommended dose of phase II study on a weekly schedule was 600 mg/m2, repeated every 2 or 3 weeks and administered via intravenous within drip infusion. PMID- 1626939 TI - [A phase II study of DWA2114R, a new platinum complex for breast cancer]. AB - A multi-institutional phase II study of DWA2114R was conducted in breast cancer. DWA2114R at doses of 800-1,000 mg/m2 was administered by 1-hour intravenous infusion every 3-4 weeks on minimal two cycles. Fifty-two patients entered the study; 34 were eligible, 7 ineligible. Eleven patients were dropped from evaluation due to incomplete observations. There were 1CR, 6PR, 1MR, 12 NC, and 14 PD with an overall response rate of 20.6%. A median duration of responses was 11 weeks. Leukopenia and nausea/vomiting were frequently observed but well tolerated and recovery was quick. It is concluded that DWA2114R is a useful drug in the treatment of breast cancer. PMID- 1626940 TI - [A phase II clinical study of cis-diammine glycolato platinum, 254-S, for advanced breast cancer]. AB - A phase II clinical study of 254-S, a new anticancer platinum complex for advanced breast cancer, was conducted by the 254-S Breast Cancer Study Group consisting of 6 institutions nation-wide. Considering the results of the phase I clinical study, 254-S was administered at 100 mg/m2 by intravenous drip infusion and this administration was repeated at least 2 times at 4-week intervals. Of 19 patients registered, 16 were evaluable for tumor response (complete cases). Partial response (PR) was obtained in 2 patients, for a 12.5% response rate. Major toxic effects observed were hematotoxicity thrombocytopenia and leukopenia, and gastrointestinal toxicity (nausea and vomiting, and anorexia), though there was no case in which the treatment with 254-S had to be discontinued due to the toxic effect. PMID- 1626941 TI - [Chromosome and DNA analyses of peripheral blood lymphocyte from the quadruple cancer patient]. AB - The patient with quadruple cancer was a 32 year-old female who had osteosarcoma, bilateral breast cancer and adenocarcinoma of the lung. When chromosomal analysis of peripheral blood lymphocyte was performed, two abnormal cells were detected among 42 cells examined. The first cell showed a translocation involving chromosome 1 and 20 and trisomic for chromosome 19. The second cell was trisomic for chromosome x. Southern blot analysis of DNA from peripheral blood lymphocyte revealed that there was no difference in the expression of Rb gene between the patient and healthy adult. PMID- 1626942 TI - [The clinical effect of cisplatin and 5-FU infusion in oral cancer]. AB - The combination chemotherapy of cisplatin and 5-fluorouracil (5-FU) is more effective than monotherapy of either drug in the head and neck cancer. In 1982, Kish reported that CF-therapy, the combination of cisplatin and 5-FU, had a high curative rate (about 82%). CF-therapy was utilized in 9 patients with carcinoma of the oral region from March, 1987 to September, 1990 in our hospital. The patients' ages ranged from 23 to 74 years old with an average of 55. All tumor were squamous cell carcinoma. There were 2 cases in stage II, 4 cases in stage III and 3 cases in stage IV. Two patients treated with only CF-therapy and the other patients treated with radiotherapy and operation in addition to CF-therapy. Our regimen is cisplatin 80-100 mg i.v. or i.a. in day 1 and 5-FU 250 mg i.a. or 5-FU 750 mg i.v. in day 2-6. The therapeutic results showed a 78% response rate to the therapy with 4 cases of CR (complete response), 3 cases of PR (partial response), 1 case of MR (minor response) and 1 case of PD (progressive disease). Side effects of cisplatin plus 5-FU (eg. nausea and vomiting) were so severe that the treatment had to the stopped in many patients. The method we have reported here was evaluated, and it is concluded that this CF-therapy is very effective as a first treatment of oral cancer. PMID- 1626943 TI - [A resected case of advanced gastric cancer with complete remission of liver metastasis by chronic daily administration of oral etoposide and UFT]. AB - An advanced gastric cancer with liver metastasis was treated with the combination MMC, Etoposide and UFT. Etoposide was administered orally at 25-50 mg/day to the gastric cancer patient with liver metastasis. In operative findings, there was no liver and lymphoid node metastasis. The gastric tumor diminished in size and changed its characteristics due to the chemotherapy. In 19 months, no liver nor LN metastasis was observed by CT scan. Presently, the patient feels well and receives outpatient treatment. PMID- 1626944 TI - [Short-term intensive consolidation chemotherapy in the treatment of acute non lymphocytic leukemia]. PMID- 1626945 TI - [Potentiation of thymidylate synthetase (TS) inhibition by combined administration of HCFU and dipyridamole: preliminary report. Kinki Cooperative Study Group of Chemotherapy for Colorectal Carcinoma]. PMID- 1626946 TI - [Cell culture and its application proliferative life span and immortalization of cultured human cells]. AB - It known that human diploid cells in culture have a limited proliferative life span (cellular senescence). Recently, evidence has accumulated that known and unknown anti-oncogenes participate in this phenomenon. Deletion or inactivation of these genes resulted in unlimited proliferation (immortalization). PMID- 1626947 TI - ["Workshop on Data Monitoring Committee in NIH"--data monitoring in cancer clinical trial]. PMID- 1626948 TI - [Trends of cancer occurrence and survival in Japan, and in Osaka]. AB - Recent improvements in cancer medical care in Osaka have resulted in the elevation of survival rates of cancer patients, except for the so-called "refractory" cancers. Five-year relative survival rates for reported patients diagnosed in 1981-1983 were higher than 60% for cancers of the breast, uterus and bladder, and around 40% for rectum, colon and stomach cancers. However, cancers of the liver, gallbladder, pancreas, and lung continued to show very low survival rates of less than 10%. In higher age-groups, advanced cases occupied a larger proportion while cases which received curative resection occupied a smaller proportion. Reflecting this, survival rates were lower in age-groups higher than 75, and the reduction of age-differences between younger and older groups was not observed during the decade. Cancer incidence for all sites in Japan was estimated by the Research Group for Population-based Cancer Registries to be 320,000 in 1985. The stomach, colorectal, lung, liver, and breast were the five leading cancer sites. According to the authors' studies, cancer incidence is projected to be 740,000 in Japan in 2015, of which 40% would be patients of "refractory" cancers and 62% would be aged patients in their upper than 70, though these were 19% and 32% in 1985. In order to combat this difficult situation in the near future, the following activities are urgently required: (1) Promotion of primary preventive measures for incurable cancers. (2) Development of specific therapy programs taking into account of QOL for aged patients as well as advanced patients. (3) Promotion of secondary preventive measures for aged people as well as younger people. PMID- 1626949 TI - [Biochemical modulation--the historical background]. AB - Biochemical modulation is a word to mean biochemical or pharmacological modulation of the efficacy or side effects of a anticancer drug. Historically, combination therapy of methotrexate (MTX) and 5-fluorouracil (5-FU) developed by Bertino et al. in 1970s has been proved to be effective to advanced gastric cancer. Many combination therapies from 1960s seem to be based on this concept of biochemical modulation. Beside MTX and 5-FU combination, currently combined use of 5-FU or other fluoropyrimidines with cisplatin (CDDP) has been studied for the treatment of cancer of the digestive organs. The therapeutic efficacies in these combination of drugs were also found to be based on biochemical or pharmacological modulation of anticancer drugs. PMID- 1626950 TI - [Mechanism of synergism and clinical results of sequential methotrexate and 5 fluorouracil in the treatment of gastric cancer]. AB - Mechanism of synergism and clinical results of methotrexate and 5-fluorouracil (MTX/5-FU) combination therapy for gastric cancer were studied. The response rate against poorly differentiated gastric cancers was 35% in this treatment. This treatment also showed a remarkable effect against cases with pleural and abdominal effusion caused by cancerous disseminations. A promising result was obtained by this treatment as neoadjuvant and postoperative chemotherapy against Borrmann type 4 gastric cancer. A greater dependence on the de novo pathway of pyrimidine synthesis against poorly differentiated gastric carcinoma, which was estimated by the fact that the thymidylate synthetase/thymidine kinase ratio was significantly higher in poorly differentiated gastric cancer than in well differentiated cancer, may potentiate therapeutic results of this treatment. PMID- 1626951 TI - [High-dose leucovorin and 5-FU]. AB - Leucovorin (LV), given intravenously the orally becomes 5, 10-methylene tetrahydrofolate in both cancer and normal cells. FdUMP which is an active metabolite of 5-FU binds tightly to thymidylate synthase in the presence of the cofactor 5, 10-methylene tetrahydrofolate. This interaction leads to potentiate the cytotoxic effect of 5-FU by prolonged inhibition of thymidylate synthase. Clinically, the combination of LV and 5-FU is given parenterally by two schedules; 5 consecutive days schedule and weekly schedule. Five 5 consecutive days-schedule is divided into 2 methods. One is a 200 mg/m2/day of LV by Machover, and the other is 20 mg/m2/day of LV by O'Connell. The weekly schedule is a 2-hour infusion of dl-LV (500 mg/m2) and iv bolus of 5-FU (600 mg/m2), given 1 hour after the beginning of LV infusion by Petrelli. A multicenter cooperative study in Japan was conducted to evaluate the clinical efficacy of LV and 5-FU using the weekly schedule by Petrelli. Response rates were 31.5% and 41.2% against advanced gastric and colorectal cancer respectively. Then, we carried out a randomized early phase II study using 250 mg/m2 of l-LV weekly (similar to the schedule of Petrelli's, armA) and 100 mg/m2 (similar to the schedule of Machover's, arm B) or 10 mg/m2 (similar to the schedule of O'Connell's, arm C) of l-LV for 5 consecutive days against gastric cancer. The response rate was 33.3% in arm A, 24.1% in arm B and no response in arm C. Toxicity was within acceptable limits, Toxic effects included diarrhea, stomatitis, anorexia and myelohypoplasia. Our data suggests that high-dose LV and 5-FU seems to be a very promising combination but, there was no responder using low dose (10 mg/m2) of l LV schedule against gastric cancer patients. PMID- 1626952 TI - [Biochemical modulation of 5-FU with interferon]. AB - A phase II clinical trials of the combination of 5-FU and interferon (IFN) were reviewed. The treatment regimen was based on the method reported by Scott Wadler, et al: 5-FU was administrated as continuous infusion at 750 mg/m2/day for 5 consecutive days and as intravenous bolus at 750 mg/m2 weekly for 7 weeks beginning on day 12. IFN was administrated subcutaneously at 9 x 10(6) I.U three times a week during weeks 1 to 8. Although the mechanism of action remains to be elucidated, some studies in immunological, pharmacokinetics, or biochemical viewpoint were reported. In this paper, the mechanisms of action related to TS and TK were introduced in biochemical viewpoint. Furthermore, side effects of IFN/5-FU combination and dual modulation of 5-FU with IFN and LV were referred. PMID- 1626953 TI - [Combined therapy with 5-FU and levamisole]. AB - Levamisole, which had been used as an insecticide for more than 20 years, was reported to have anticancer effects as an immunopotentiator. Among many clinical trials with this agent, Moertel and his colleagues reported excellent results in Dukes-C colon cancer patients treated with 5-FU and levamisole in 1990. In this paper, results of our animal experiments would be reported in conjunction with the review of the recent clinical trials. PMID- 1626954 TI - [Clinical significance of serum CA 125 values in patients with gastric cancers- especially correlation with peritonitis carcinomatosa]. AB - A study of 387 patients with gastric cancers revealed elevation of CA 125 in sera of 7.2% of the patients. Patients with Borrmann 1 and 2 in gross type, poorly differentiated adenocarcinoma in histological type and stage 4 in stage grouping of gastric cancer, showed a higher positive rate than patients with the others. In patients with peritonitis carcinomatosa, positive rate of serum CA 125 was 42.9% of patients with synclonus metastasis, 72.2% with metaclonus metastasis. Elevation of serum CA 125 was observed earlier than detection by image diagnosis in almost all cases. These results indicate that CA 125 is an useful tumor marker for detection and follow up of patients with peritonitis carcinomatosa from gastric cancers. PMID- 1626955 TI - [Combination chemotherapy of solid tumor--effects of hyaluronidase on doxorubicin (DXR) penetration into multicellular tumor spheroids (MTS)]. AB - We have studied the effects of hyaluronidase (HYD) on the penetration and cell kill effect of doxorubicin (DXR) using multicellular tumor spheroids (MTS). MTS of approximately 500 microns in diameter were prepared by liquid over lay culture technique from PC-10 lung and HEp-2 laryngeal squamous carcinoma cell lines. Cells in MTS and monolayer were exposed for various durations to HYD, followed by 1 hr, rest interval, and by 1 hr. exposure to DXR. MTS and monolayer cells were then trypsinized to a single cell suspension and subjected to clonogenic assay. For PC-10 MTS, pretreatment with HYD for 24 hr. resulted in approximately 10-fold increases in DXR cell kill effects as compared to DXR alone. HEp-2 MTS were more sensitive to HYD pretreatment. Thus, 1 hr. exposure to HYD produced approximately 4-fold increases in DXR-induced cell lethality. Fluorescent microscopic study revealed that 1hr. exposure of MTS to DXR produced DXR fluorescence only 1-2 outer layer of MTS. When MTS were pretreated with HYD, there was an enhanced penetration of DXR fluorescence into the MTS core. HYD-induced enhancement of DXR penetration and its cell kill effect was dependent on the exposure time and tumor cell origin. PMID- 1626956 TI - [Analysis of cell proliferation kinetics and the effects of cisplatin on the cell cycle of human gastric cancer cells by autostage cytofluorometry]. AB - Analysis of both cell proliferation kinetics and effects of cis diamminedichloroplatinum (CDDP) on cell cycle in human gastric cancer cell line (HGC-Y2) by measuring the contents of nuclear DNA, RNA and the Ki-67 antigen using autostage cytofluorometry system was described. In HGC-Y2 cells, RNA content increased during the cell cycle and reached to the maximum at G2/M phase. The results of pulse treatment with CDDP on these cells demonstrated a prolongation of S phase and G2 arrest with increasing of RNA content of these cells. We classified the cells by intranuclear distribution pattern of Ki-67 antigen and thus could identified the cells at G0 and M phases from these classification. The content of Ki-67 antigen was moderate grade at G1 phase and it decreased in the early S phase, then increased gradually during S phase and at the late S phase. It increased rapidly, reaching to the maximum at G2/M phase. After CDDP treatment, the content of Ki-67 antigen increased in the cells in prolonged S phase and in the cells arrested at G2 phase. It was also found that the syntheses of both Ki-67 antigen and RNA were not inhibited by CDDP. These results suggest that the method using autostage cytofluorometry system was useful for the research, on the mechanism of cancer therapy because of making possible to analyze precisely the cell cycle and the influence of anticancer drugs. PMID- 1626957 TI - [Comparison of surgical therapy and combined irradiation in rectal cancer--second report. Effect of irradiation and ACNU on the tumor]. AB - As part of a joint study on preoperative radiotherapy for developing an optimal mode of rectal cancer therapy, ACNU sensitization was studied in a total of 120 cases, with the cooperation of 48 facilities participating nationwide. The following results were obtained. Improvement in depth of invasion was more distinct in the combination preoperative therapy-ACNU group than in the preoperative radiotherapy group, with no other significant differences between the two. This finding suggests that dose and administration method could be improved. White blood cells and platelets were reduced in some cases of the ACNU combination group, but these reductions were not serious enough to impede surgical procedures. In addition, no significant difference in complications was noted between the two. PMID- 1626958 TI - Skeletal hyperostosis in patients receiving chronic, very-low-dose isotretinoin. AB - BACKGROUND AND DESIGN: We conducted a prospective roentgenographic survey of patients participating in a randomized, placebo-controlled, multicenter clinical trial that evaluated the effectiveness of chronic, very-low-dose (approximately 0.14 mg/kg per day for 3 years) isotretinoin in preventing the subsequent occurrences of new basal cell carcinoma in patients with previous basal cell carcinoma. To assess potential skeletal changes, a sample of 269 patients from among a total of 981 enrollees were randomly selected for comparative roentgenographic review. Baseline and 36-month roentgenograms of the cervical and thoracic spine of each patient were read side by side by a radiologist, masked to treatment group, who noted both the presence and extent of abnormalities at each vertebral level at baseline and the progression of existing or occurrence of new abnormalities at previously unaffected levels at 36 months. RESULTS: In comparison with the placebo group, significantly more patients in the isotretinoin group exhibited progression of existing hyperostotic abnormalities (40% vs 18%; P less than .001) and new hyperostotic involvement at previously unaffected vertebral levels (8% vs 1%; P = .015). CONCLUSION: Our findings indicate that chronic, very-low-dose isotretinoin can induce hyperostotic axial skeletal changes similar to those reported in patients taking higher doses. PMID- 1626959 TI - Ultraviolet-B phototherapy for early-stage cutaneous T-cell lymphoma. AB - BACKGROUND AND DESIGN--Cutaneous T-cell lymphoma (CTCL) is a slowly advancing disease that initially presents in the skin and may later progress to involve the lymph nodes and viscera. Since CTCL most often presents on non-sunlight-exposed regions of the body, a possible protective role for UVB irradiation has been suggested. Recent observations have also found that UVB irradiation serves an immunoregulatory role. Given that limited data are available regarding the use of UVB phototherapy in treating CTCL, a retrospective nonrandomized study of 37 nonconsecutive patients with early CTCL was performed to assess the efficacy of UVB phototherapy in the treatment of CTCL. RESULTS--Twenty-five (71%) of the 35 patients treated with UVB phototherapy (two were unavailable for follow-up) achieved a total clinical remission. Median time to remission was 5 months, and median duration of the remission was 22 months. Twenty-five (83%) of 30 patients with disease limited to patches achieved remission, whereas none of the patients with plaque-level disease achieved a remission. Of the 25 patients who achieved complete remission, five (20%) had a recurrence of CTCL. CONCLUSIONS- Phototherapy with UVB appears to be effective in patients with early patch-stage CTCL. PMID- 1626960 TI - Reticulated black solar lentigo ('ink spot' lentigo). AB - BACKGROUND AND DESIGN: Pigmented lesions that are black and have an irregular outline are often considered suspicious for melanoma; however, these features may be seen in benign lesions. The reticulated black solar lentigo is such a lesion and is described in a clinicopathologic study of nine lesions in eight patients. RESULTS: The "ink spot" lentigo is distinguished clinically by its color and wiry or beaded, markedly irregular outline. It has a reticulated pattern and most resembles a spot of ink on the skin. In this series of patients, the lesions were limited to sun-exposed areas of the body and had a distribution pattern similar to that of solar lentigines. Although all the patients were of Celtic ancestry and had numerous solar lentigines, they usually had only one black lentigo (range, one to four; mean, 1.6; median, one). Histologic evaluation, including electron microscopy and dopa-incubated vertical sections, demonstrated lentiginous hyperplasia of the epidermis, marked hyperpigmentation of the basal layer with "skip" areas that involved the rete ridges, and a minimal increase in the number of melanocytes. CONCLUSIONS: Because of their dark color, irregular border, and limited number, reticulated black solar lentigines were of concern to patients and primary care physicians. However, the characteristic features of these lesions allow one to make the clinical diagnosis of a benign lentigo. PMID- 1626961 TI - Prevalence and significance of acanthosis nigricans in an adult obese population. AB - BACKGROUND AND DESIGN: Acanthosis nigricans develops commonly in obese individuals, yet its prevalence and significance in an unselected adult obese population has not been determined. To address these issues, 34 patients enrolled in the Adult Obesity Clinic at Parkland Memorial Hospital (Dallas, Tex) were chosen at random and examined. RESULTS: Acanthosis nigricans was observed in fully 74% of patients; its prevalence correlated positively with severity of obesity. Black obese patients demonstrated a greater propensity for manifesting the cutaneous disorder than did white obese individuals. Patients with acanthosis nigricans exhibited fasting plasma insulin levels that were markedly higher than those of nonacanthotic cohorts. CONCLUSIONS: Obesity is a significant risk factor for the development of acanthosis nigricans. Conversely, acanthosis nigricans is a reliable cutaneous marker of hyperinsulinemia in obese individuals. PMID- 1626962 TI - Controlled localized heat therapy in cutaneous warts. AB - BACKGROUND: Controlled localized heating as a method of superficial tissue destruction has been used in veterinary medicine for the treatment of benign and malignant tumors. The rationale for its use is that the diseased tissue being treated is more sensitive to the effects of heating than is normal tissue. This technology was applied to the treatment of common hand warts in a placebo controlled study. OBSERVATIONS: Twenty-nine warts were treated one to four times (median, two times) at 50 degrees C for 30 to 60 seconds. Twenty-five (86%) of 29 treated verrucae regressed completely while seven (41%) of 17 control warts resolved during the course of the study. No wart that regressed regrew during the follow-up period (mean, 15.6 weeks). CONCLUSIONS: Controlled localized heating can cause the regression of hand warts. The 86% regression rate compares favorably with other wart treatment modalities. The mechanism of action and the effect of heat on these virally induced tumors is not known but may involve direct antiviral effects, physical destruction of the tumor, or the promotion of an inflammatory response that ultimately eradicates the lesion. PMID- 1626963 TI - Dermatologic features of the superior vena cava syndrome. AB - BACKGROUND: The superior vena cava syndrome occurs when extrinsic compression or intraluminal occlusion impedes blood flow through this vessel. The most common underlying cause is a malignant neoplasm, especially a bronchogenic carcinoma. This article describes the cutaneous findings of this disorder. OBSERVATIONS: Among the earliest and most prominent features are numerous, dilated, vertically oriented, and tortuous cutaneous venules or veins above the rib cage margin. Recognition of this cutaneous sign allowed us to make a diagnosis of lung cancer in several patients. Other features include upper body edema and ruddiness or cyanosis, distended neck veins, proptosis, and conjunctival suffusion. CONCLUSIONS: Detecting the characteristic cutaneous features can lead to an early diagnosis of the superior vena cava syndrome. These skin changes usually represent indirect dermatologic signs of an underlying malignant neoplasm; for most patients, this syndrome is the initial manifestation of their cancer. The most common cause is a bronchogenic carcinoma, especially the small-cell variety, but others include lymphomas, primary mediastinal tumors, and metastases to the mediastinal lymph nodes from extrathoracic primary tumors, especially breast cancer. Treatment of the underlying malignant neoplasm and relief of the obstruction produce prompt improvement in the dermatologic findings. PMID- 1626964 TI - Cutaneous nerves in cafe au lait spots with white halos in infants with neurofibromatosis. An electron microscopic study. AB - BACKGROUND AND DESIGN: Although two cardinal skin manifestations of neurofibromatosis are cutaneous neurofibromas and cafe au lait spots, the pathogenesis of cafe au lait spots are very poorly known compared with that of cutaneous neurofibromas. Thus, the cafe au lait spots in two Japanese infants were clinically, histologically, and electron-microscopically investigated. OBSERVATIONS: Some of the cafe au lait spots in the mongolian spots were surrounded by white halos. Histologically, in the cafe au lait spots, the epidermal basal cells had abundant melanin pigment, but macromelanosomes were not seen throughout the epidermis. In the white halo, the epidermal basal cells had a small amount of melanin pigment. Electron microscopically, the cafe au lait spots and their white halos had many subepidermal and intraepidermal nerves that belonged to free nerve endings. All the cutaneous nerves were mature. Some of the intraepidermal nerves had partially or completely naked axons that contacted tightly with the cytomembranes of the basal keratinocytes. Some of the axons in the subepidermal nerves showed degenerative changes only in the white halos. No ultrastructural pathologic changes were observed in the melanocytes, the epidermal keratinocytes, or melanosomes in those cells in the cafe au lait spots and their white halos; also, dermal melanocytes were absent in the both areas. CONCLUSIONS: The increase of the cutaneous nerves and the absence of dermal melanocytes in the cafe au lait spots and their white halos may be considered as characteristic histologic cutaneous findings in infants with neurofibromatosis. However, no evidence indicates that the cutaneous nerves may participate closely in the pathogenesis of the white halos. PMID- 1626965 TI - Multiple primary cutaneous plasmacytomas. AB - BACKGROUND: Cutaneous plasmacytoma is an uncommon tumor and is mostly seen in the context of end-stage multiple myeloma. Only 20 cases of primary cutaneous plasmacytoma have been documented. A significant proportion of these patients went on to develop systemic disease with a poor prognosis. In a number of patients, however, the abnormal clone of plasma cells may arise in the skin and never progress to multiple myeloma involving the bone marrow. OBSERVATIONS: We describe a patient who developed multiple primary cutaneous plasmacytomas after a possible insect bite reaction. The monoclonality of the tumor cells is demonstrated using immunohistochemical techniques. He has been treated vigorously with chemotherapy and local radiotherapy and remains well 3 years after diagnosis. Bone marrow has been harvested for use as an autologous bone marrow transplant in the event of systemic relapse. CONCLUSIONS: Unlike previous reports of this rare entity, this case documents the monoclonality of tissue plasma cells with immunohistochemical techniques. As cutaneous plasmacytomas have been reported with an early significant mortality, unlike extramedullary plasmacytomas elsewhere, we have advocated combination chemotherapy and cryopreservation of uninvolved bone marrow for future autologous bone marrow transplantation should systemic myelomatosis develop in the patient. PMID- 1626966 TI - Amyloidosis cutis dyschromica. DNA repair reduction in the cellular response to UV light. AB - BACKGROUND: Amyloidosis cutis dyschromica, a special type of primary cutaneous amyloidosis, is assumed to be a congenital disorder and sun exposure is thought to be the major causal factor. Herein we report a case of this rare disease and DNA repair characteristics of UV damages in the fibroblasts derived from the patient. OBSERVATIONS: A 24-year-old Japanese woman showed hyperpigmented and hypopigmented xerotic lesions in sun-exposed skin since she was 10 years old; deposits of amyloid material were detected in the papillary dermis. The fibroblasts were hypersensitive to UV-B, but not so sensitive to UV-C. Unscheduled DNA synthesis of the patient's cells after UV-C exposure was lower than that of normal cells at 3 hours and both reached the same level at 6 hours. After UV-B exposure, unscheduled DNA synthesis of the patient's cells was lower than that of normal cells at least until 6 hours after UV exposure. CONCLUSION: Although the origin of amyloidosis cutis dyschromica is unknown, hypersensitivity to UV-B with possible DNA repair defects is suggested to be the cause of this disease. PMID- 1626967 TI - Isotretinoin does not prevent basal cell carcinoma. PMID- 1626968 TI - Vesicular lesions in a woman with progressive systemic sclerosis. Penicillamine induced intradermal vesicles: an example of human lathyrism. PMID- 1626969 TI - An intensive care unit nurse with a recurring annular lesion. Erythema annulare centrifugum (EAC). PMID- 1626970 TI - An erythematous nodular eruption. Secondary syphilis. PMID- 1626971 TI - Giant inflammatory targetoid plaques. Granuloma annulare (GA). PMID- 1626972 TI - Anti-liver-kidney microsome type 1 antibodies in lichen planus. PMID- 1626973 TI - Becker's nevus and ipsilateral breast hypoplasia--androgen-receptor study in two patients. PMID- 1626974 TI - Treatment of hyperkeratotic skin diseases with R 68151, a topical 5-lipoxygenase inhibitor: four case reports. PMID- 1626975 TI - Efficacy of ivermectin in the therapy of cutaneous larva migrans. PMID- 1626976 TI - Papular mucinosis and human immunodeficiency virus infection. PMID- 1626977 TI - Successful treatment of an antimony-resistant American mucocutaneous leishmaniasis: a case report. PMID- 1626978 TI - Cutaneous necrosis induced by injection of hydrocarbons. PMID- 1626980 TI - Metaphysical urticaria. PMID- 1626979 TI - Repigmentation of leukotrichia by epidermal grafting and systemic psoralen plus UV-A. PMID- 1626981 TI - Paediatric cochlear implantation. AB - Cochlear implantation may now be considered as a method of managing children with profound sensory hearing loss who do not benefit from conventional amplification. It involves a team approach with integration of many skilled individuals, as well as the child and his or her parents and family. As William House has said, in 1991, 'The future is not in the adult programme, but in the continued expansion of the children's programme'. PMID- 1626983 TI - Stressful life events and childhood illness. PMID- 1626982 TI - Detection of minimal residual disease in leukaemia. PMID- 1626984 TI - The Scottish low birthweight study: II. Language attainment, cognitive status, and behavioural problems. AB - Of the 636 survivors of a total geographically based population born in Scotland in 1984, who weighed less than 1750 g at birth, 611 (96%) were assessed at 4.5 years to determine the prevalence of language, cognitive, and behavioural problems. Language development was significantly related to birth weight, gestational age, and social class for comprehension, less so for expressive language. Mean (SD) intelligence quotient (IQ) on the British ability scales was 92.9 (14.7). Within this population there were no significant differences between birthweight groups. Overall they performed poorly on visual recognition, verbal comprehension and number skills subscales--in the latter those with birth weights less than 1000 g were significantly worse than the heavier children. Only 5% had IQs less than 70, but a further 3% could not be tested because of other physical disability. Among those with normal IQs were groups of children who exhibited patterns of skill deficits in different subscales raising the possibility of specific learning difficulties. Poor attention span was reported in 47%, and parents said the study children had more behavioural problems than their siblings. PMID- 1626985 TI - Impaired motor function (clumsiness) in 5 year old children: correlation with neonatal ultrasound scans. AB - All 155 surviving children from a cohort of 200 very low birthweight infants originally studied in 1984-5 were traced. These infants had careful sequential ultrasound examinations in the neonatal period. The children were examined again at entry into school at 5 years of age. The test of motor impairment (TOMI) and the vocabulary subscale of the Wechsler preschool and primary scale of intelligence (WPPSI) were administered to 152 of the index cohort and 144 control children of the same age in the same class at school. Twelve of the cohort had cerebral palsy, but eight of these were in mainstream schools. The index group scored significantly higher on both the TOMI and the WPPSI subscale compared with the controls. The index cases were subdivided on the basis of their neonatal ultrasound scans into four groups: group 1, consistently normal; group 2, 'prolonged flare'; group 3, germinal matrix haemorrhage-intraventricular haemorrhage (GMH-IVH), without parenchymal haemorrhage, but no evidence of prolonged flare; and group 4, both GMH-IVH and prolonged flare. The group of index children with consistently normal ultrasound scans had a higher TOMI and lower WPPSI compared with their controls. There was a statistically significant increase in the TOMI subscore 1 (manual dexterity) in group 4 infants compared with group 1, but not differences between the other groups. Regression analysis suggests that neither prolonged flare nor GMH-IVH has an important individual contribution to the variation, but the low birth weight does have a significant relationship with motor impairment. It appears that relatively minor ultrasound appearances such as prolonged flare and GMH-IVH are associated with motor impairment (clumsiness) at 5 years, but this has a small effect compared with low birth weight. PMID- 1626986 TI - Postdischarge formula consumption in infants born preterm. AB - In 31 infants born preterm and formula fed ad libitum, all milk intake was weighed from hospital discharge to nine months post-term. Mean daily milk intake was high, reaching 230 g/kg before four weeks post-term and was still over 150 g/kg beyond six months. Five of the 31 infants (16%) consumed 300-350 g/kg; 50% 'voluntarily' consumed more than upper recommended limits for energy intake and 35% did so for protein intake. PMID- 1626987 TI - Computed tomography findings in partial seizures. AB - The computed tomography findings in 82 children with partial seizures of unknown aetiology were reviewed. All had seizures with predominantly focal motor phenomena and none had abnormality on neurological examination. Findings on computed tomography were normal in 64 children (78%) and abnormal in 18 children (22%). Fourteen children had changes representing static pathology (mainly cerebral atrophy) which did not influence patient management but four had potentially correctable lesions (two tumours and two arteriovenous malformations). There were no correlations between seizure control, seizure duration, intellectual handicap, postictal weakness, electroencephalographic findings, and abnormality on the computed tomogram. In particular, none of these features were useful in predicting the presence of a tumour or arteriovenous malformation. It is concluded that a computed tomogram is indicated in every child with partial seizures. PMID- 1626988 TI - Difficult and unlikeable parents. AB - Children of parents who are perceived as difficult or unlikeable are at risk of receiving less good medical care. Therefore a postal questionnaire was sent to 100 hospital doctors dealing with children asking which features made them consider a parent to be difficult or unlikeable. Seventy eight responded. Most problems arose from parents who displayed aggression, disparagement of their child, unacknowledged anxiety, or fixed ideas about the medical condition and its management. Other unpopular parental features were poor compliance, failure to listen, and the attendance of more than one accompanying adult. Respondents graded 16 features in order of their detrimental effect on the child's care. A major factor was if the child had a condition for which the doctor could offer no treatment; less important was the fact that the child might have a condition not understood by the doctor. Parents originating from the Indian subcontinent posed additional problems, in particular the common unavailability of interpreters. Doctors of all grades understood why parents behaved in awkward ways, but lacked strategies for dealing with them. A similar survey of nurses and therapists produced a poor response (51% returns). Only the most senior acknowledged that some parents were difficult or unlikeable and that, as a consequence, the child's care might be affected. Nurses acknowledged difficulty with parents who were violent or who abused their children physically. PMID- 1626989 TI - Asthma, inhaled corticosteroid treatment, and growth. AB - To evaluate the effects on growth of inhaled corticosteroid treatment (ICT) and of the quality of control of asthma, height velocity was studied in 58 prepubertal children attending a specialist asthma clinic because of chronic asthma that was difficult to control. The height velocity standard deviation (SD) score was maximal when the asthma was well controlled both before (0.01) and after (-0.07) starting ICT. It was least when the asthma was poorly controlled both before (-1.50) and after (-1.55) starting ICT. The effectiveness of control correlated significantly with the height velocity SD score, both before and after ICT was started. No evidence was found that the administration of ICT has an adverse effect on growth. PMID- 1626990 TI - Tartrazine in atopic eczema. AB - Multiple double blind placebo controlled challenges with tartrazine 50 mg (three challenges) and glucose placebo (three challenges) were performed in 12 children with atopic eczema aged 1 to 6 years. The children were selected on the basis of severity (regular clinic attenders) and a parental history that tartrazine provoked worsening of the eczema. In only one patient did the three tartrazine challenge periods correspond with the highest symptom scores or the highest physician observer scores, and the probability of this occurring by chance in one or more patients out of 12 was 0.46. In this sample we were unable to confirm intolerance to tartrazine in 11 out of 12 patients. PMID- 1626991 TI - Frontoethmoidal meningoencephalocele: a common and severe congenital abnormality in South East Asia. AB - The clinical features of 23 cases of fronto-ethmoidal meningoencephalocele are described in two South East Asian populations. The clinical, embryological, and epidemiological evidence may support an early teratogenic insult in the aetiology of this congenital defect. PMID- 1626992 TI - Early diagnosis and management of 5 alpha-reductase deficiency. AB - Two siblings of Pakistani origin, karyotype 46 XY, were born with predominantly female external genitalia with minute phallus, bifid scrotum, urogenital sinus, and palpable gonads. The older sibling at the age of 8 days showed an adequate testosterone response to human chorionic gonadotrophin (hCG) stimulation. The diagnosis of 5 alpha-reductase deficiency was made at age 6 years when no 5 alpha reduced glucocorticoid metabolites were detectable in urine even after tetracosactrin (Synacthen) stimulation. In the younger sibling the diagnosis of 5 alpha-reductase deficiency was provisionally made at the early age of 3 days on the basis of high urinary tetrahydrocortisol (THF)/allotetrahydrocortisol (5 alpha-THF) ratio and this ratio increased with age confirming the diagnosis. Plasma testosterone: dihydrotestosterone (DHT) ratio before and after hCG stimulation was within normal limits at age 3 days but was raised at age 9 months. Topical DHT cream application to the external genitalia promoted significant phallic growth in both siblings and in the older sibling corrective surgery was facilitated. In prepubertal male pseudohermaphrodites with normal or raised testosterone concentrations, phallic growth in response to DHT cream treatment could be an indirect confirmation of 5 alpha-reductase deficiency. PMID- 1626993 TI - Salivary IgA antigliadin antibody as a marker for coeliac disease. AB - In recent years, serum antibodies to gliadin (AGA) have been reported to be useful markers of coeliac disease. IgA AGA have also been found in intestinal secretions and saliva in coeliac disease and may offer a convenient, non-invasive screening test. In order to test this hypothesis, salivary and serum AGA were measured in children with coeliac disease proved by biopsy and compared with several control groups. Measurement of salivary IgA AGA provided excellent discrimination between those children with coeliac disease and the control groups, and our study suggests that it may provide a rapid, non-invasive method of screening for this disease before intestinal biopsy. PMID- 1626994 TI - Family characteristics and insulin dependent diabetes. AB - During the calendar year of 1988 a survey of new cases of insulin dependent diabetes mellitus (IDDM) in children under the age of 15 years in the British Isles was conducted. After cases had been confirmed and permission obtained to contact the families, postal questionnaires were sent to the parents of children diagnosed in England, Wales, Northern Ireland, and the Republic of Ireland. Children who developed diabetes were significantly more likely to be heavier at birth in comparison with national reference data. The diabetic children were less likely to have been breast fed, and there were more children than expected whose fathers were in nonmanual occupations. Where there was a first degree relative with IDDM there were positive correlations between the age at diagnosis of the index cases and that of their diabetic fathers and their diabetic siblings, but not their diabetic mothers. A higher proportion of children than expected who were diagnosed under the age of 5 years had fathers with IDDM. Characteristics of family members associated with IDDM in children that might provide pointers to the aetiology of the disease include heavier birth weight, method of infant feeding, the age at onset of IDDM in affected fathers and affected siblings, and the family lifestyle as defined by social class of the father. PMID- 1626995 TI - IgG antibodies in early Pseudomonas aeruginosa infection in cystic fibrosis. AB - The relationship between IgG antibodies to Pseudomonas aeruginosa and its isolation from sputum was determined in 100 patients with cystic fibrosis observed at intervals of two months for a median period of one year. Only one patient had a raised antibody titre (greater than 22.9 ELISA units) before isolation of P aeruginosa. Initially 65 patients were antibody negative, of whom 48 were also culture negative. Of 24 patients with positive sputum culture and negative antibodies, seven became antibody positive at a median (range) 15 (6-25) months later. The remaining 17 patients continued antibody negative until the end of the study at a median range 15 (1-123) months after becoming culture positive. This latter group were younger and had more intermittently positive sputum cultures. In general positive IgG antibody titres do not predate isolation of P aeruginosa, but in some patients are present soon after acquisition of infection. A positive titre indicates significant exposure to P aeruginosa and could be used to detect infection in patients unable to produce sputum and possibly indicate the effect of early antipseudomonal treatment. PMID- 1626996 TI - The value of proximal small intestinal biopsy in the differential diagnosis of chronic diarrhoea. AB - The value of proximal intestinal mucosal biopsy was reviewed in 381 children presenting with chronic diarrhoea over an eight year period. An enteropathy was detected in 44% of cases and was more frequently seen in those aged less than 6 months. A diagnosis was established in 91% of cases. The most common diagnosis was the postenteritis syndrome where the presence of an enteropathy indicated those requiring treatment with a cows' milk free diet. Other conditions where a biopsy facilitated diagnosis or treatment included giardiasis, enteropathogenic Escheriichia coli, crytosporidiosis, autoimmune enteropathy, and microvillous atrophy. Coeliac disease was considered in 55% of children and established in 8%, clearly identifying those requiring a gluten free diet. This also emphasises the important role of the biopsy procedure in the exclusion of specific diseases. Proximal small intestinal mucosal biopsy is an essential investigation in children with chronic diarrhoea in whom an enteropathy is suspected. PMID- 1626997 TI - Dealing with the courts and parenting breakdown. PMID- 1626998 TI - Child health and paediatric care in Spain: where are we going? PMID- 1626999 TI - Statistics from the inside. 6. Data structures (continued). PMID- 1627000 TI - Asthma: a follow up statement from an international paediatric asthma consensus group. PMID- 1627001 TI - Beta glucuronidase and hyperbilirubinaemia in breast fed infants of diabetic mothers. PMID- 1627002 TI - The value of the Medicare cost report. PMID- 1627003 TI - Regarding one-inch needles for peritoneal dialysis medications. PMID- 1627004 TI - Response on NSAIDs article. PMID- 1627005 TI - Renal physiology series: Part 2 of 8. Glomerular filtration and renal hemodynamics. AB - The formation of urine is a process that begins with glomerular filtration and is greatly influenced by changes in renal hemodynamics. Selective filtration of the blood is possible because of the unique characteristics of the glomerulus and renal circulation. Many factors interact to maintain a consistent blood flow, allowing filtration and urine formation to continue despite systemic changes in blood pressure. Factors that impact on renal hemodynamics include the autoregulatory mechanism, the renin-angiotensin mechanism, eicosanoids, kinins, the sympathetic nervous system, catecholamines, antidiuretic hormone, dopamine, histamine, endothelin, endothelium-derived relaxing factor, and atrial natriuretic peptide. Knowledge of the effects of these factors will allow the nephrology nurse to predict, identify, and assist in the treatment of clinical conditions that can alter renal hemodynamics and glomerular filtration. PMID- 1627006 TI - Tidal peritoneal dialysis vs. continuous cyclic peritoneal dialysis: children's preference. AB - The purpose of this survey was to determine if the shorter dialysis time of tidal peritoneal dialysis (TPD) was valuable enough to warrant additional training time and machine assembly. The subjects included 6 children ranging in age from 5-16 years and their parents. Children and parents were taught to use an automated cycler system to provide TPD. Dialysis was limited to 8 hours and overday volumes minimized. Prescriptions were altered to prevent uremia and maintain clearances of urea and creatinine at prior continuous cyclic peritoneal dialysis (CCPD) levels. At 6 months, subjects were surveyed. Subjects felt comfortable with TPD within 6 weeks of training. They preferred the shorter dialysis time. All asked to remain on TPD, which has improved the quality of life for these children and their families by decreasing the amount of time required for dialysis. PMID- 1627007 TI - A case illustration of family management style in childhood end stage renal disease. AB - Families of children with end stage renal disease (ESRD) experience their situation based on how they define the illness, manage it, and view the consequences of the illness on the family and individual family members. The purpose of this study was to describe how a family with a child with ESRD defined and managed their situation. Interviews with individual family members from two separate interview sessions were analyzed. The family's management style changed from struggling to adaptive over a 1-year period following the child's kidney transplant. PMID- 1627008 TI - A peer support group for adolescent dialysis patients. AB - Adolescents with chronic renal failure face unique problems often best understood by peers with the same condition. An adolescent peer support group can be a valuable tool to foster peer relationships and enhance self-esteem. Moreover, nurses can learn to be effective group leaders. PMID- 1627009 TI - Machine cleaning and disinfecting. PMID- 1627010 TI - Peritoneal dialysis patient completes successful pregnancy. AB - This patient was able to meet seven of the expected outcomes. Her weight and nutritional status improved after initiating CAPD, which she performed safely and effectively. She closely monitored her vital signs and appropriately notified the obstetrician when her blood pressure became elevated. She maintained proper fluid balance. The patient was successfully treated for exit site infection with antibiotics. She self-administered intraperitoneal antibiotics for peritonitis successfully. In spite of the infections, hypertension, and poor nutrition, the patient was able to complete her pregnancy to the 35th week and delivered a small, but healthy infant. Frequent monitoring and a team approach to S.B.'s well being contributed greatly to her delivery of a viable infant. The education and training provided by the nephrology nurses was a key element in the successful management of the patient. PMID- 1627011 TI - Oral iron therapy with ferrous fumarate and polysaccharide iron complex. AB - Oral iron replacement therapy with Chromagen, containing ferrous fumarate, and Niferex, containing polysaccharide iron complex, can successfully maintain hematologic and iron indices in dialysis clients and demonstrated fewer adverse effects in selected clients. Their multiple ingredient dose forms, which further support erythropoiesis, and their possible decrease in distressing side effects should enhance client compliance, making these two drugs excellent alternatives to traditional iron therapies. PMID- 1627012 TI - Case management of the anemic patient. Epoetin alfa: focus on inflammation and infection. AB - Response to Epoetin alfa can be influenced by several factors, including the presence of inflammation or infection. It is important that nurses monitor patients so that possible undesirable effects of inflammation or infection can be avoided or minimized. PMID- 1627013 TI - ANNA. Directory of nephrology nurse researchers. PMID- 1627014 TI - Qualitative research: beyond open-ended questions. PMID- 1627016 TI - Declining interest in internal medicine. Preliminary vs categorical residents as role models. PMID- 1627015 TI - Primary prevention of coronary heart disease with drug therapy. Safety and total mortality issues. PMID- 1627017 TI - A critical appraisal of ticlopidine, a new antiplatelet agent. Effectiveness and clinical indications for prophylaxis of atherosclerotic events. AB - BACKGROUND: Recommendations are broadening for the prophylaxis of atherosclerotic disorders, but aspirin is the only widely used agent. Ticlopidine hydrochloride, a new antiplatelet medication, has recently been approved for prescription in North America. We reviewed the major clinical trials of ticlopidine and derived guidelines for its use. METHODS: Studies of ticlopidine were sought through MEDLINE for 1980 to 1990 and through bibliographies of retrieved articles. All published, randomized trials of ticlopidine were appraised if they reported major morbidity and mortality as primary end points. All eligible studies were formally reviewed by an expert panel according to published principles for critical appraisal of the medical literature. Both benefits and risks were quantified. RESULTS: Four randomized trials reported major clinical end points. In these, ticlopidine was more effective than placebo for preventing recurrences after completed stroke; was more effective than aspirin for patients with transient ischemic attacks and partial strokes; and reduced vascular death and nonfatal myocardial infarction in an open trial among patients with unstable angina. For patients with intermittent claudication ticlopidine, was not significantly better than placebo for preventing myocardial infarction or stroke. Side effects were more common with ticlopidine than with aspirin or placebo. CONCLUSIONS: Ticlopidine should be prescribed in place of aspirin for stroke prophylaxis or unstable angina if the patient is unable to tolerate aspirin. Ticlopidine may also benefit patients who experience new ischemic events while taking aspirin or, probably, patients with peripheral vascular disease. A complete blood cell count should be performed every 2 weeks during the first 3 months of therapy to check for leukopenia. PMID- 1627018 TI - Modulators of coagulation. A critical appraisal of their role in sepsis. AB - Widespread intravascular coagulation is common in patients with sepsis. Coagulation abnormalities may result from exposure to endotoxin, from tumor necrosis factor alpha or interleukin 1 release, or from the actions of a more specific mediator, such as vascular permeability factor. The result is marked activation of the contact and coagulation systems; simultaneously, there is decreased fibrinolysis and depressed levels of the inhibitors of the contact and coagulation systems. Multiple agents are being studied to correct these abnormalities. Antithrombin III holds promise because it inhibits a number of factors important in contact and coagulation activation, not just thrombin. Plasminogen activators may prove helpful in increasing fibrinolysis during sepsis; because they have been associated with rebound thrombin generation, however, plasminogen activators may be most effective if used in conjunction with hirudin or a synthetic hirudin analogue. Bradykinin may offset hypotension in sepsis. Protein C may inhibit thrombin formation and also complex with plasminogen activator inhibitor 1, thereby promoting fibrinolysis. Other agents that may prove effective include alpha 1-antitrypsin Pittsburgh, C1-esterase inhibitor, monoclonal antibodies to contact factors, soybean trypsin inhibitors, thrombomodulin, prostaglandin I2, and aprotinin. There are no data to support the use of heparin or fibronectin, except in limited circumstances. PMID- 1627019 TI - Atypical roentgenographic manifestations of Pneumocystis carinii pneumonia. AB - Although Pneumocystis carinii pneumonia (PCP) usually presents with bilateral interstitial pulmonary infiltrates, many other roentgenographic presentations occur in human immunodeficiency virus-infected patients. To clarify the determinants of atypical presentations of PCP, we evaluated 65 English-language reports that related the roentgenographic manifestations of consecutive cases of PCP. The incidence of PCP-associated upper lobe disease, cysts, and spontaneous pneumothoraxes was increased in human immunodeficiency virus-infected patients receiving aerosolized pentamidine prophylaxis. Normal chest roentgenograms were more common and nodular lesions were less common in human immunodeficiency virus infected patients than in uninfected patients. However, the roentgenographic manifestations of PCP could not be specifically predicted by a patient's underlying disease. Neither zidovudine therapy nor intravenous drug use apparently affected the roentgenographic presentation of PCP. Unusual pathologic responses to PCP, including granuloma formation, vascular invasion, and microscopic foci of calcification, were present in all patient groups. PMID- 1627020 TI - The Lipid Research Clinics Coronary Primary Prevention Trial. Results of 6 years of post-trial follow-up. The Lipid Research Clinics Investigators. AB - BACKGROUND: Participants in the Lipid Research Clinics Coronary Primary Prevention Trial, a randomized, cholesterol-lowering trial comparing cholestyramine (N = 1907) vs placebo (N = 1899) treatment in 35- and 59-year-old asymptomatic hypercholesterolemic men, conducted between 1973 and 1983, were followed up annually from 1985 until 1989. Post-trial treatment was not provided. METHODS: Eleven predefined hypotheses pertaining to possible benefits and adverse effects of in-trial cholestyramine treatment were tested by standard statistical comparisons of the two original Coronary Primary Prevention Trial treatment groups (cholestyramine and placebo). RESULTS: Similar increasing proportions of cholestyramine and placebo used cholesterol-lowering drugs post-trial. After 13.4 years of in-trial plus post-trial follow-up, there were 13 (143 vs 156) fewer deaths in the cholestyramine group than in the placebo group. Although not statistically significant, the mortality hazard ratio (0.89) was similar to that in other cholesterol-lowering trials. This trend, a result of reduced coronary heart disease mortality, occurred despite a post-trial narrowing of the in-trial cholestyramine-placebo difference in coronary heart disease incidence from 32 (155 vs 187) to 16 (268 vs 284). The cholestyramine and placebo groups had similar 13.4-year mortality rates from cancer, other medical causes, and trauma and similar cancer incidence rates. However, 13.4-year incidences of benign colorectal tumors (50 vs 34), cancer of the buccal cavity and pharynx (eight vs two), gallbladder disease (68 vs 53), and gallbladder surgery (58 vs 40) were nonsignificantly increased in the cholestyramine group. CONCLUSION: Overall, 6 years of post-Coronary Primary Prevention Trial follow-up have not provided conclusive evidence of benefit or long-term toxicity of cholestyramine treatment beyond that evident at the cessation of the trial. PMID- 1627021 TI - A possible protective effect of nut consumption on risk of coronary heart disease. The Adventist Health Study. AB - BACKGROUND: Although dietary factors are suspected to be important determinants of coronary heart disease (CHD) risk, the direct evidence is relatively sparse. METHODS: The Adventist Health Study is a prospective cohort investigation of 31,208 non-Hispanic white California Seventh-Day Adventists. Extensive dietary information was obtained at baseline, along with the values of traditional coronary risk factors. These were related to risk of definite fatal CHD or definite nonfatal myocardial infarction. RESULTS: Subjects who consumed nuts frequently (more than four times per week) experienced substantially fewer definite fatal CHD events (relative risk, 0.52; 95% confidence interval [CI], 0.36 to 0.76) and definite nonfatal myocardial infarctions (relative risk, 0.49; 95% CI, 0.28 to 0.85), when compared with those who consumed nuts less than once per week. These findings persisted on covariate adjustment and were seen in almost all of 16 different subgroups of the population. Subjects who usually consumed whole wheat bread also experienced lower rates of definite nonfatal myocardial infarction (relative risk, 0.56; 95% CI, 0.35 to 0.89) and definite fatal CHD (relative risk, 0.89; 95% CI, 0.60 to 1.33) when compared with those who usually ate white bread. Men who ate beef at least three times each week had a higher risk of definite fatal CHD (relative risk, 2.31; 95% CI, 1.11 to 4.78), but this effect was not seen in women or for the nonfatal myocardial infarction end point. CONCLUSION: Our data strongly suggest that the frequent consumption of nuts may protect against risk of CHD events. The favorable fatty acid profile of many nuts is one possible explanation for such an effect. PMID- 1627022 TI - Does computed tomographic brain imaging have a place in the diagnosis of dementia? AB - BACKGROUND: Computed tomographic (CT) scanning of the head is an accepted routine in the evaluation of dementia. This study attempted to identify a patient group in which brain imaging adds meaningful data to the clinical picture. METHODS: One hundred patients who met criteria for dementia as defined in the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, underwent computed tomographic imaging. From clinical data alone, 56 of these patients also met the following strict criteria for the diagnosis of probable Alzheimer's disease (PAD): the McKhann criteria for PAD, Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, criteria for primary degenerative dementia, a score of less than 4 on the modified Hachinski Ischemia Scale, a normal neurologic examination and symptoms for at least 1 year. RESULTS: In the PAD group, eight scans (14%) had abnormalities other than atrophy; only three (two showing lacunae and one showing infarct) were of possible clinical significance. In the 44 patients not meeting PAD criteria, 23 scans (52%) were abnormal, including 15 with infarcts, two with periventricular lucencies, three showing tumors, and one showing hydrocephalus. CONCLUSIONS: These results support the diagnostic value of computed tomographic scanning in atypical dementia and its limited utility in PAD. The data indicate that clinical guidelines can be developed for the application of CT in the diagnosis of dementia. PMID- 1627023 TI - Neurologic syndrome in 25 workers from an aluminum smelting plant. AB - BACKGROUND: This article expands on an earlier series of three patients with a neurologic syndrome, who had all worked in an aluminum smelting plant. METHODS: Twenty-five symptomatic workers from the same plant were referred for a standardized evaluation, including completion of a health questionnaire, neurologic examination, and neuropsychologic evaluation. An exposure index was calculated for each worker based on level and duration of exposure in the potroom, where exposures were the greatest. This index was correlated with symptoms, signs, and neuropsychologic test scores. RESULTS: Twenty-two (88%) of the patients reported frequent loss of balance, and 21 (84%) reported memory loss. Neurologic examination revealed signs of incoordination in 21 (84%) of the patients. Neuropsychologic test results showed preservation in certain spheres of functioning, such as verbal IQ, with substantial impairment in others, particularly memory functioning. On memory tests, 70% to 75% showed mild or greater impairment. The majority (17 of 19 tested, or 89%) showed depression on the Minnesota Multiphasic Personality Inventory. The exposure index was significantly correlated with signs and symptoms of incoordination. CONCLUSIONS: This study and others in humans and animals support the existence of a syndrome characterized by incoordination, poor memory, impairment in abstract reasoning, and depression. Aluminum exposure in the potroom seems the most likely cause. PMID- 1627024 TI - Risk of needlesticks and occupational exposures among residents and medical students. AB - PROBLEM: Occupational exposure to human immunodeficiency virus (HIV) disease is a problem of concern to all health care workers, especially those in large urban teaching hospitals with large numbers of HIV-positive patients. METHOD: The self reported incidence of needlesticks and other exposures to patients' blood and body fluids in 550 medical students and residents at the Los Angeles County University of Southern California Medical Center during the 1989 through 1990 training year was studied by means of an anonymous survey. RESULTS: Seventy-one percent of respondents reported one or more needlesticks or other exposures during the training year. Surgical residents had a sixfold greater rate of occupational exposure compared with medicine residents and were significantly more likely to experience suture needlesticks, cuts, open wound contamination, and mucous membrane exposure. Medical students generally were at somewhat lower risk compared with residents, but had greater rates of hollow-needle puncture accidents. No trend was found for accidental exposure by level of residency training. The known HIV-positive exposure rate for students and residents was 9.5% per person per year. Only 9% of exposures were actually reported to the health center. CONCLUSIONS: Based on the rate of exposures reported, numbers of known and estimated HIV-positive patients, and previously published HIV seroconversion rates, we would expect an annual rate of HIV seroconversion rates, we would expect an annual rate of HIV seroconversion as a result of occupational exposures of between 27 and 46 per 100,000. This rate is similar to the leading cause of death in this age group--motor vehicle accidents--and is equivalent to one student or resident in this medical center seroconverting every 2 to 3 years. Although only a portion of accidental exposures are regarded as preventable, these data emphasize the importance of increased efforts toward improved education, prevention, and accessibility of protective equipment. PMID- 1627025 TI - Nosocomial acquisition of beta-lactamase--negative, ampicillin-resistant enterococcus. AB - BACKGROUND: A recent prospective study at the Department of Veterans Affairs Medical Center, Martinez, Calif, revealed that 9% of enterococcal clinical isolates were ampicillin resistant. We prospectively studied 100 patients hospitalized in one general medicine ward and in the medical intensive care unit to study determinants of acquisition of ampicillin-resistant enterococcus. METHODS: Rectal swabs and urine cultures were obtained from patients within 72 hours of admission to the study ward and twice weekly until discharge from the ward or the intensive care unit. Cultures were obtained from the hands of personnel and from environmental surfaces in the general medical ward and the intensive care unit. Ampicillin-resistant enterococcal isolates were examined for molecular relatedness by plasmid DNA analysis. RESULTS: The cultures from 23 patients yielded ampicillin-resistant enterococci. The rectal swabs yielded ampicillin-resistant enterococci before the urine cultures did except in one patient whose urine and rectal cultures were both positive on the same day. Acquisition of ampicillin-resistant enterococci was significantly associated with previous antimicrobial agents, Foley catheterization, and being bedridden. Resistant enterococci were not isolated from hospital personnel or environmental surfaces. Plasmid analysis by gel electrophoresis demonstrated nine strains, two of which predominated. Rectal and urine isolates from the same patient had identical plasmid electrophoresis patterns. CONCLUSIONS: We conclude that ampicillin-resistant enterococci are common in the rectal flora, can spread to the urinary system, are associated with patient characteristics that predipose to nosocomial infection, and may become an emerging clinical problem. PMID- 1627026 TI - Cost and quality effects of alternative treatments for persistent gastroesophageal reflux disease. AB - BACKGROUND: Gastroesophageal reflux disease is commonly encountered by general internists and gastroenterologists. METHODS: We used decision analysis to assess the clinical and economic effects of three treatments--phase 1 therapy alone or combined with omeprazole or ranitidine hydrochloride therapy--for patients with persistent, symptomatic grade 2 or higher gastroesophageal reflux disease. To the maximum extent possible, data were obtained from the published literature. We convened an expert consensus panel to estimate specific data points when they were unavailable or contradictory in the literature, including estimates of optimal and actual clinical practice patterns. A 7-month model was used to correspond to the time frame of available clinical trial data. The perspective of the analysis was that of the payer. The costs of medical care for various clinical outcomes were based on actual mean payments made by Independence Blue Cross of Philadelphia and Pennsylvania Blue Shield. RESULTS: Although the retail payments for daily omeprazole therapy are the highest among the three interventions tested, it produced both the lowest expected overall payments for medical care and the most effective strategy for treating symptoms during the 7 month model. Omeprazole therapy was consistently approximately $1800 less costly than ranitidine therapy and $2700 less costly than phase 1 therapy alone during the period examined, regardless of whether empiric or nonempiric treatment strategies were used. Even when payments for major complications (the most important cost variable) were reduced by 80%, omeprazole therapy resulted in payments 17% and 22% lower than those associated with ranitidine therapy and phase 1 therapy alone, respectively. Omeprazole also produced the most symptom free months during the 7-month follow-up period. The clinical and economic outcomes of performing an initial diagnostic workup, compared with treating patients empirically, were equal. CONCLUSIONS: We conclude that omeprazole therapy is the preferred initial therapeutic approach for patients with persistent, symptomatic gastroesophageal reflux disease in whom phase 1 therapy fails. Assessment of long-term approaches must await the results of extended clinical studies. PMID- 1627027 TI - Descriptive epidemiology of agranulocytosis. AB - BACKGROUND: To determine the incidence of agranulocytosis, a descriptive epidemiologic study was performed. METHODS: With the use of computerized Medicaid billing data from 1980 through 1985 from Minnesota, Michigan, and Florida, the ratio of persons hospitalized with a discharge diagnosis of neutropenia to persons with any claim for medical service was first used as an estimate of the incidence rate of the condition. Patients with cancer and patients receiving cytotoxic and immunosuppressive drugs were excluded. The information provided by a review of medical records for a subset of neutropenia cases was used to determine the proportion with neutropenia after excluding cases with recurrent or chronic neutropenia, and to determine the proportion with agranulocytosis. RESULTS: The incidence rates (95% confidence intervals) of agranulocytosis, excluding recurrent or chronic disease, were 2.3 (1.4 to 3.7), 7.7 (6.6 to 8.9), and 15.4 (11.3 to 20.4) per million per year in each state, respectively. The overall incidence was 7.2 (6.3 to 8.1) per million per year. CONCLUSIONS: Agranulocytosis is an extremely uncommon condition. The excess risk of agranulocytosis due to any drug other than cytotoxic drugs must, therefore, be very low. PMID- 1627028 TI - Prevalence of measles susceptibility in hospital staff. Evidence to support expanding the recommendations of the Immunization Practices Advisory Committee. AB - BACKGROUND: In 1989 and 1990, measles reached epidemic proportions in the United States, including several areas of California. Children's Hospital Oakland (Calif), a major health care provider for children in a measles epidemic area of California, reported 131 cases between 1989 and 1991, the largest number ever reported by that institution. In February 1990, four cases of measles were reported among hospital staff. Continued risk of nosocomial infection prompted the development of a program to ensure that all hospital staff were adequately protected against measles. METHODS: All hospital employees who were unable to document proof of measles immunity were required to be serologically screened for measles antibody and to be vaccinated against measles if they were determined to be nonimmune. Serologic screening was performed in-house with a commercially available enzyme-linked immunosorbent assay measles antibody test. Dates of birth were recorded for all employees screened. Individuals with negative or repeatedly equivocal results were considered to be nonimmune and were vaccinated with trivalent measles-mumps-rubella vaccine. RESULTS: Between March and June 1990, 1694 staff were serologically tested for measles antibody. Eighty-nine (5.3%) of the employees were considered to have inadequate immunity. Forty (45%) of these susceptible individuals were born before 1957. CONCLUSIONS: We conclude that the recommendations of the Immunization Practices Advisory Committee should be expanded to include serologic screening or vaccination of hospital personnel who were born before 1957. Serologic screening of hospital staff may be a reasonable alternative to vaccination under certain circumstances. PMID- 1627029 TI - Ethical considerations in living organ donation and a new approach. An Advance Directive Organ Registry. AB - Living organ donation should be recognized as an ethical compromise to the principle of nonmaleficence (doing no harm), given the risks healthy donors are allowed to assume. Living organ donation should be reserved for situations in which there is no acceptable alternative. Increasing the availability of cadaveric organs is most desirable, since it would decrease (although probably not eliminate) the need for living organ transplantation and would provide organs (ie, hearts) that could not otherwise be obtained. We propose the development of an incentive-based Advance-Directive Organ Registry, in which all adults are encouraged to register their advance directive regarding organ donations. Those individuals agreeing to permit usable organs to be taken at the time of death would receive priority for organs generated by the program, should a transplant become necessary when there is a shortage of organs. The proposed Advance Directive Organ Registry is firmly founded on the principles of autonomy, beneficence, and justice. PMID- 1627030 TI - Serum cholesterol level and mortality findings for men screened in the Multiple Risk Factor Intervention Trial. Multiple Risk Factor Intervention Trial Research Group. AB - BACKGROUND: With increased efforts to lower serum cholesterol levels, it is important to quantify associations between serum cholesterol level and causes of death other than coronary heart disease, for which an etiologic relationship has been established. METHODS: For an average of 12 years, 350,977 men aged 35 to 57 years who had been screened for the Multiple Risk Factor Intervention Trial were followed up following a single standardized measurement of serum cholesterol level and other coronary heart disease risk factors; 21,499 deaths were identified. RESULTS: A strong, positive, graded relationship was evident between serum cholesterol level measured at initial screening and death from coronary heart disease. This relationship persisted over the 12-year follow-up period. No association was noted between serum cholesterol level and stroke. The absence of an association overall was due to different relationships of serum cholesterol level with intracranial hemorrhage and nonhemorrhagic stroke. For the latter, a positive, graded association with serum cholesterol level was evident. For intracranial hemorrhage, cholesterol levels less than 4.14 mmol/L (less than 160 mg/dL) were associated with a twofold increase in risk. A serum cholesterol level less than 4.14 mmol/L (less than 160 mg/dL) was also associated with a significantly increased risk of death from cancer of the liver and pancreas; digestive diseases, particularly hepatic cirrhosis; suicide; and alcohol dependence syndrome. In addition, significant inverse graded associations were found between serum cholesterol level and cancers of the lung, lymphatic, and hematopoietic systems, and chronic obstructive pulmonary disease. No significant associations were found of serum cholesterol level with death from colon cancer, with accidental deaths, or with homicides. Overall, the inverse association between serum cholesterol level and most cancers weakened with increasing follow up but did not disappear. The association between cholesterol level and death due to cancer of the lung and liver, chronic obstructive pulmonary disease, cirrhosis, and suicide weakened little over follow-up. CONCLUSIONS: The association of serum cholesterol with specific causes of death varies in direction, strength, gradation, and persistence. Further research on the determinants of low serum cholesterol level in populations and long-term follow up of participants in clinical trials are necessary to assess whether inverse associations with noncardiovascular disease causes of death are consequences of noncardiovascular disease, whether serum cholesterol level and noncardiovascular disease are both consequences of other factors, or whether these associations are causal. PMID- 1627031 TI - Herpes simplex virus associated with recurrent Stevens-Johnson syndrome. A management strategy. AB - We describe a 36-year-old man with recurrent Stevens-Johnson syndrome, which became progressively more severe over a 13-year period. His episodes were apparently preceded by herpes simplex virus oral mucosal infections. A management protocol, including immediate therapy with acyclovir and prednisone at the onset of herpes simplex virus oropharyngitis, is outlined. This management strategy has successfully prevented four subsequent episodes of progression to Stevens-Johnson syndrome. Thus, Stevens-Johnson syndrome associated with herpes simplex virus may be prevented by early use of acyclovir and prednisone. PMID- 1627032 TI - Cutaneous oxalosis after long-term hemodialysis. AB - A 27-year-old woman undergoing long-term hemodialysis developed cutaneous calcifications on her fingers. A skin biopsy specimen showed that the deposits were calcium oxalate. To our knowledge, only one previous article has reported pathologic and crystallographic studies on calcifications of the skin resulting from dialysis oxalosis. We speculate that vitamin C supplements, liberal tea consumption, an increased serum ionized calcium concentration, and the long duration of hemodialysis contributed to the production of these deposits. PMID- 1627033 TI - Nonsteroidal anti-inflammatory drug-associated pulmonary infiltrates with eosinophilia. Review of the literature and Food and Drug Administration Adverse Drug Reaction reports. AB - OBJECTIVE: The purpose of this study was to detail the clinical and pathologic presentation of pulmonary infiltrates with eosinophilia (PIE) associated with nonsteroidal anti-inflammatory drug use. METHODS: We reviewed case reports and Food and Drug Administration Adverse Drug Reaction Spontaneous Reporting Program reports. RESULTS: A case of pulmonary infiltrates with eosinophilia related to naproxen use was studied. Six similar cases from the medical literature and 22 reports from the Food and Drug Administration were reviewed. Four cases of PIE associated with ibuprofen, obtained from the Food and Drug Administration, and single literature reports of PIE associated with fenoprofen and sulindac detailed similar clinical presentations. The clinical presentation of PIE syndrome associated with nonsteroidal anti-inflammatory drugs included fever, cough, dyspnea, infiltrates on chest roentgenogram, and an absolute peripheral eosinophilia. Pathologic examination revealed poorly defined granulomas with infiltrating eosinophils. CONCLUSIONS: Naproxen and other nonsteroidal anti inflammatory drugs can elicit the PIE syndrome. The prevalence of this side effect is likely underestimated, given the extensive use of these drugs and the relatively benign course of PIE syndrome. PMID- 1627034 TI - Use of spontaneous reporting system data. PMID- 1627035 TI - Futile cardiopulmonary resuscitation. PMID- 1627037 TI - Goals of medicine. PMID- 1627036 TI - Cardiopulmonary resuscitation and the dying patient with cancer: a resuscitator's response. PMID- 1627038 TI - Goals of medicine. PMID- 1627039 TI - Patient-induced pulmonary embolism. PMID- 1627040 TI - Pericardial drainage vs pericardial 'window'. PMID- 1627041 TI - Autosplenectomy complicating pneumococcal meningitis in adults. PMID- 1627042 TI - Do fluoroquinolones alter the effects of warfarin therapy? PMID- 1627043 TI - Limbic system abnormalities identified in schizophrenia using positron emission tomography with fluorodeoxyglucose and neocortical alterations with deficit syndrome. AB - A hypothesis of psychosis localization in schizophrenia was derived from studying metabolic alterations in rat brain in response to phencyclidine hydrochloride administration. Since phencyclidine and its selective agonist dizocilpine maleate (MK801) induced overlapping and long-lasting metabolic alterations predominantly in limbic areas, the hypothesis developed that schizophrenic patients with psychosis would evidence functional abnormalities in limbic circuits compared with normal controls. Accordingly, 12 actively psychotic, drug-free patients with schizophrenia and matched normal controls underwent functional brain scans using positron emission tomography and fluorodeoxyglucose. Regions of interest were identified on five matched axial slices in each patient and control subject, and average metabolic rates were calculated. Patients with schizophrenia showed a significantly lower regional cerebral metabolic rate of glucose in the hippocampus and the anterior cingulate cortex than did normal controls, but not in neocortical areas or in the extrapyramidal system. When the group of schizophrenic patients was divided into deficit and nondeficit types, a preliminary exploratory analysis suggested thalamic, frontal, and parietal cortical hypometabolism in the deficit subgroup, with normal metabolism in the nondeficit patient group in those areas; in contrast, hippocampal and anterior cingulate cortical metabolism was reduced in both deficit and nondeficit subtypes. These results suggest that the limbic system, especially the hippocampus, is functionally involved in schizophrenic psychosis and that different manifestations of schizophrenia may involve different neuronal circuits. PMID- 1627044 TI - Volumes of ventricular system subdivisions measured from magnetic resonance images in first-episode schizophrenic patients. AB - In vivo brain imaging and postmortem investigations have demonstrated structural anomalies in the brains of schizophrenic patients. However, previous studies have not established clear relationships between the characteristic symptoms of the disorder and neuropathologic changes in specific brain regions. We have obtained high-resolution magnetic resonance brain images of first-episode schizophrenic and normal control subjects and, with a computerized mensuration system, determined the volumes of the different components of the entire ventricular system. Volumes of ventricular segments were significantly larger in patients than controls (differences ranged from 17% to 40%). Temporal horn enlargement consistently demonstrated significant correlations with a broad range of schizophrenic symptoms. Our data indicate that anomalies of limbic structures in the medial temporal lobe surrounding the temporal horn play a crucial pathophysiologic role in schizophrenia. PMID- 1627045 TI - Preliminary data on the metabolic brain pattern of patients with winter seasonal affective disorder. AB - The brain metabolic pattern of patients with winter seasonal affective disorder with and without light treatment was determined by positron emission tomography. Compared with controls, patients with seasonal affective disorder with and without light treatment had globally lower metabolic rates, relatively lower superior medial frontal cortex rates, and somewhat higher basal ganglia rates. Patients receiving light treatment had a relatively higher rate in an occipital region of interest containing the primary visual cortex. Patients without light treatment had relatively higher metabolic rates in right parietal and medial orbitofrontal cortex and lower rates in the left parietal cortex. Patients not receiving light treatment had a hemispheric metabolic asymmetry (left greater than right) for the midprefrontal cortex located 67 mm above the canthomeatal line. The right side of this region, previously found reduced in manic-depressive illness and schizophrenia, was decreased primarily in patients with seasonal affective disorder with fewer atypical depressive symptoms. These "abnormal" prefrontal and parietal cortex regions appeared highly "coupled" in the patients with seasonal affective disorder. PMID- 1627046 TI - Magnetic resonance imaging of the caudate nuclei in depression. Preliminary observations. AB - A role of the caudate nucleus in depression has been suggested from relevant clinical conditions, such as patients with Huntington's disease or caudate infarcts, as well as animal studies. Correlations of caudate nucleus disease with depressive symptoms have been limited to autopsy studies and cases of gross pathological disorder, such as large infarcts. We used serial axial high-field magnetic resonance images and an unbiased stereological technique to estimate the volumes of the caudate nuclei in 50 patients who met DSM-III criteria for major depression (23 men, 48.3 +/- 17 years old) in comparison with 50 age- and gender matched normal controls free of major neurological and psychiatric disorders. Depressed patients had smaller caudate nucleus volumes (5.2 +/- 1.6 cm3) compared with controls (6.2 +/- 1.7 cm3). Right and left caudate nucleus volumes were smaller in depressed patients compared with controls. Age was negatively correlated with caudate nucleus volumes in depressed patients as well as in controls. Caudate nucleus volumes in depressed patients were inversely correlated with the bicaudate and bifrontal indices. These results may be the first demonstration of diminished caudate nucleus volumes in depression and suggest a role for the caudate nucleus in the pathogenesis of major depression. PMID- 1627047 TI - Neuroendocrine aspects of primary endogenous depression. XI. Serum melatonin measures in patients and matched control subjects. AB - To ascertain the extent of dysregulation of melatonin secretion in endogenous depression, we measured nocturnal and diurnal serum melatonin concentrations in 38 depressed patients (23 women and 15 men) who had primary, definite endogenous depression according to the Research Diagnostic Criteria and in 38 individually matched normal control subjects. Previous reports have suggested that such patients may have reduced nocturnal melatonin secretion, often in conjunction with increased hypothalamic-pituitary-adrenal cortical axis activity. This has been considered as a possible reflection of reduced noradrenergic activity in depression. Compared with their matched controls, the depressed patients showed a trend toward a significantly elevated average nocturnal melatonin concentration that was accounted for primarily by the 14 premenopausal women--the postmenopausal female and male depressive patients did not differ significantly from their respective controls. The average diurnal melatonin concentration also showed a trend toward being higher in both the female and male depressed patients. The melatonin measures were not consistently related to any of the previously reported hypothalamic-pituitary-adrenal cortical axis measures in these subjects. Our findings thus failed to confirm a "low melatonin syndrome" or an inverse relationship between nocturnal melatonin and nocturnal cortisol concentrations in depression. This discrepancy may be related to methodologic differences among studies; our data are in accord with those findings of the one other reported study in which normal controls were individually matched to patients on variables that were known to influence melatonin secretion. Most of the studies, including ours, have been cross-sectional.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627048 TI - Urinary excretion of catecholamines and their metabolites in relation to circulating catecholamines. Six-hour infusion of epinephrine and norepinephrine in healthy volunteers. AB - Some depressed patients have been shown to excrete abnormal amounts of catecholamines and their metabolites in urine. Some studies suggest that hypersecretion of epinephrine by the adrenals and of norepinephrine by the peripheral sympathetic system cause increased excretion of urinary catecholamines and their metabolites in a subgroup of patients. To evaluate the effect of increased catecholamine levels in the peripheral circulation on urinary catecholamine and metabolite levels, we infused healthy volunteers during 6 hours with epinephrine, norepinephrine, or placebo, respectively, in a three-period, double-blind, crossover design. The results indicate that (1) urinary epinephrine and norepinephrine levels were the most sensitive indicators of increased circulating epinephrine and norepinephrine levels, respectively; (2) changes in circulating epinephrine or norepinephrine levels were not readily reflected in changes in urinary vanillylmandelic acid or 3-methoxy-4-hydroxyphenylglycol levels; and (3) increased normetanephrine excretion was not only induced by infusion of norepinephrine but also by epinephrine. This last finding may be due to activation of the sympathetic nervous system by circulating epinephrine. These results may help to explain the mechanism of adrenal epinephrine and sympathetic nervous system norepinephrine hypersecretion observed in subgroups of depressed patients. PMID- 1627049 TI - The 'anatomy' of research funding of mental illness and addictive disorders. AB - To assess the level and sources of research funding for mental illness and substance abuse fields, we undertook a systematic survey of public and private funding entities. Applying standard definitions, we found that research support in these fields totaled approximately $859 million in fiscal 1988. This level of research support for mental illness and substance abuse is extremely limited and disproportionate to the overall costs to society by these disorders. Mental disorders and substance abuse accounted for $66.8 billion in health care costs in 1988; in the same year, research on these disorders represented only 4.7% of all health research support nationwide. The three institutes of the Alcohol, Drug Abuse, and Mental Health Administration (ADAMHA) (namely, the National Institute of Mental Health [NIMH], the National Institute of Drug Abuse [NIDA], and the National Institute on Alcoholism and Alcohol Abuse [NIAAA]) support 64% of all mental illness and substance abuse research; other federal agencies add little more than 7.5%, with the Department of Veterans Affairs the largest at 2%. The pharmaceutical and hospital industries account for another 17% of all support; state funding is 8%, which is particularly surprising in light of the states responsibility for the chronically mentally ill. While there has been recent significant growth in the research budgets of the NIMH, the NIDA, and the NIAAA, other sectors have not grown commensurately, leaving the field vulnerable to the funding vicissitudes of these institutes. Greater coalition building and advocacy are necessary to expand the breadth and depth of research resources for the field.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627050 TI - Fluoxetine, akathisia, and suicidality: is there a causal connection? PMID- 1627051 TI - Thyroid function and partial sleep deprivation response. PMID- 1627052 TI - Psychosurgical treatment of obsessive-compulsive disorder. PMID- 1627053 TI - Methodological issues in the assessment of human immunodeficiency virus-related cognitive impairment. PMID- 1627054 TI - Thought disorder ratings distinguish between diagnostic groups. PMID- 1627055 TI - Role of antenatal care in reducing maternal mortality. AB - Maternal mortality in the developed nations has been considerably reduced, but it still is very high in developing nations. I carried out an indepth study of maternal mortality at N. Wadia Maternity Hospital, Bombay. India, from 1929 to 1988, which revealed that the MMR which was 1920 per 100,000 live births during 1929-1939 period has declined to 82 per 100,000 live births during 1980-1988 period. This achievement in reduction of maternal mortality over the decades was due to multiple factors like increased and effective antenatal, intranatal, and postnatal care. This study shows the apathy of pregnant women to come forward to avail of antenatal care though available even free of charge nearby. To give maximum benefits to pregnant women specially in the developing nations, we have to carry the antenatal care at the door-steps of the community. PMID- 1627056 TI - Meconium aspiration syndrome: the role of resuscitation and tracheal suction in prevention. AB - We reviewed our experience of meconium staining of liquor and meconium aspiration syndrome over a 33 month period. The clinical and radiological severity of disease was assessed in comparison with tracheal suction and resuscitation. Sixty (27%) of newborns with meconium stained liquor subsequently developed MAS. No association was found between the thickness of meconium or its presence on tracheal aspiration with subsequent severity of respiratory disease. However, the presence of meconium in the trachea was strongly associated with radiological abnormality. The severity of meconium aspiration syndrome and mortality were also related to the clinical stability of the infants at presentation. Our results indicate that intrauterine aspiration and pulmonary maladaptation may play a significant role in meconium aspiration syndrome rather than resuscitative events at delivery. PMID- 1627057 TI - Bilateral ovarian cysts in a newborn: a case report. AB - Large ovarian cysts in the fetus are uncommon. Ultrasonography has helped in the detection of these cysts antenatally and in the newborn female infant. A case of bilateral ovarian cysts in a newborn is presented. The choice of management between conservative measures and surgical approaches remains controversial. PMID- 1627058 TI - Chorionic villus sampling: evaluation of obstetric performance. AB - Chorionic villus sampling is frequently utilised in the Nottingham region as a means of early prenatal diagnosis of genetic problems. Its relative safety in the early antenatal period is well established but there has been some concern that perinatal mortality may be greater in the chorionic villus sampling group as compared to amniocentesis. We have in response studied our own data and report the obstetric outcome in 144 cases where the pregnancy has progressed beyond 28 weeks gestation. We have selected a procedure free control group matched for parity. We have found no significant difference in the perinatal outcome and obstetric performance and conclude that at this juncture we should continue to offer our services as chorionic villus sampling offers significant advantages in the first trimester over amniocentesis. PMID- 1627059 TI - Perinatal mortality in high risk pregnancy: a prospective study of preventable factors. AB - The present study was undertaken to identify the preventable factors operative in high fetal and neonatal losses. Over a period of one year, of total of 1,600 consecutive deliveries, 1,107 were considered to be at-risk: there were 33 fetal and 31 early neonatal deaths with an overall perinatal mortality rate of 40/1,000 births. Perinatal mortality was higher in mothers who had received inadequate antenatal care and/or with bad obstetric history. Major maternal and obstetric factors associated with a high PMR were: advancing maternal age and parity, antepartum hemorrhage, diabetes, anemia, instrument and vaginal breech delivery. Overall cesarean section rate was 16.9%. Infants with a gestational age of less than 37 weeks and/or of birth weight of less than 2,500 g contributed for 56.2% and 68.7% of the total perinatal losses respectively. PMR was three fold higher among twins compared with singleton births. Identifiable causes of perinatal deaths observed were: asphyxia (31%), congenital anomalies (18.7%), sepsis (18.7%) and low birth weight (25%). It would appear that preventable factors are operative in over two third of the cases of perinatal loss and better maternal health, obstetric and neonatal care can improve the perinatal outcome in majority of the cases. PMID- 1627060 TI - A study on the placental transport mechanism of vitamin K2 (MK-4). AB - The present study was primarily concerned with in vitro investigation of vitamin K2 (MK-4) transport using human placental villous tissues, with the objective of elucidating the placental transport mechanism of vitamin K2. 1. When vitamin K2 (MK-4) was not administered to gravidae, the observed concentrations of vitamin K2 were 0.32 +/- 0.07 ng/ml in the maternal venous blood, undetectable in umbilical venous blood, and 1.01 +/- 0.37 ng/g wet tissue in the placental villous tissue. 2. When vitamin K2 was administered to gravidae, (20 mg/day x 7 days per os), the corresponding concentrations were 0.89 +/- 0.21 ng/ml in the maternal venous blood, 0.18 +/- 0.06 ng/ml in umbilical venous blood, and 5.38 +/ 1.05 ng/g wet tissue in the placental villous tissue. 3. In vitro studies using placental villous tissue indicated that vitamin K2 transport into villous tissue is not active, but suggested the existence of a highly vitamin K2 specific transport system in the human placenta. On the other hand, the results of comparison studies of transport of vitamin K2 and vitamin K1 into villous tissue indicated that transport activity with respect to the former vitamin was higher. Moreover, comparison of vitamin K2 transport into villous tissue at the end of the first trimester and at full term revealed that transport was somewhat higher during the final stage. In summary, the above results indicated that whereas transport of vitamin K1 into the fetus is not especially pronounced, transport into the placental villous tissue is comparatively good. PMID- 1627061 TI - Ectopic ovary in the omentum. AB - At caesarean section the right ovary of a patient was found to be absent. There was an omental cyst that was excised and this was found to be an ectopic ovary. This case is reported because of its rarity. The nomenclature and embryological aspects of the condition are discussed. PMID- 1627062 TI - Government-funding program on reversal of tubal sterilization. AB - Three hundred and sixty-one women were provided government-funded sterilization reversal services with the technique of microsurgery. A large majority of reasons (89.8%) for requesting reversal surgery was a loss of children, and the mean interval between sterilization and reversal was 28.7 months. Two hundred and seven (69.7%) of 297 follow-up cases have experienced term delivery or intra uterine pregnancy and 5 cases were ectopic pregnancy. The largest number of reversal clients (63.3%) were sterilized by the laparoscopic unipolar coagulation technique and the next largest group (24.2%) was sterilized by the laparoscopic banding technique. The highest pregnancy rate (77.8%) was shown in clients who had undergone laparoscopic banding technique while the lowest (65.9%) was the group of laparoscopic unipolar coagulation. A more than 60% of the clients became pregnant within 6 months of their reversal surgery, with the shortest interval being 1 month, the longest 39 months, and the mean 7.6 months. A large majority of the successful cases, 81.6%, were pregnant within 1 year of their reversal surgery. PMID- 1627063 TI - Immunohistochemical assessment of the growth fraction in cervical cancers using the monoclonal antibody Ki-67; relationship to the clinical stage, histologic type and DNA content. AB - To assess the growth potential of cervical cancer, cell populations in proliferating cycle (%PC) were examined by an immunohistochemical technique using the monoclonal antibody Ki-67. The %PC was 31.63 +/- 16.61% in 36 cervical cancers and was significantly higher when compared to the 7.8 +/- 3.81% found in 24 samples of normal ectocervical tissues. In cervical cancer tissues, the %PC increased in accordance with progression of the clinical stage of the disease, however, the %PC was not different among the various histologic types of invasive cervical cancers. The DNA index also increased in accordance with progression of the clinical stage of cervical cancer, however, there was no correlation between the %PC and the DNA index. These results suggest that the value of %PC obtained using the monoclonal antibody Ki-67 can be used as a parameter for evaluating the growth activity of cervical cancer and for predicting biological heterogeneity in a tumor. PMID- 1627064 TI - Changes in bone mineral density and fracture prevalence in Japanese women after oophorectomy. AB - The bone changes after gynecological surgery during the early phase of recovery were examined. The subjects were randomly selected from women who had undergone bilateral oopho-hysterectomies (OOX, n = 98, 46.0 +/- 5.0 year-old) or hysterectomies (HX, n = 75, 43.6 +/- 4.6 year-old) within 4 years prior to entering the study. The ovarian functions in the HX group were presumed to be intact following the hysterectomies, judging from the cytological evaluation of the vaginal pap smears. The bone morphological changes in both groups were examined to measure the cortical thickness of the metacarpal bone (MCI) on hands X-ray film using microdensitometry, and the posterior/anterior height ratios (P/A ratio) of the entire vertebral bodies, on vertebral X-ray films using a digitizer. The changes in bone mineral densities in both groups were measured by dual energy X-ray absorptiometry at lumbar vertebrae (L2-4 BMD) and by microdensitometry at the metacarpal cortical bone; the bone densities of metacarpal bone were referenced by the density of aluminum step wedge on the same X-ray films. The prevalence of vertebral body fractures (P/A ratio greater than 1.4) in the OOX group (5.1%) was 3.9 times higher than that in the HX group (1.3%). There was a significant decrease in MCI in the OOX group compared with the HX group (p less than 0.01). L2-4 BMD in the OOX and HX group were 1.07 +/- 0.15 and 1.16 +/- 0.13 g/cm2, respectively (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627065 TI - Direct posterior composite resin restorations: a review. 2. Clinical technique. AB - Despite the increased use of composite resin to restore posterior teeth, there is evidence that clinicians should be selective in their use of these restorations. This paper describes the clinical technique--preparatory procedures, preparation of the cavity, preparation for placement of composite resin, placement of composite resin and finishing of the restoration--for the relatively conservative use of composite resin in posterior teeth and reviews the literature to discuss briefly many of the controversial aspects of the technique. PMID- 1627066 TI - Massive bleeding following maxillofacial trauma. Case report. AB - A case is reported of massive haemorrhage following severe maxillofacial trauma. The various procedures that were used to control the bleeding are discussed with particular reference to therapeutic arterial embolization. PMID- 1627067 TI - Anterior maxillary supernumerary teeth: a clinical and radiographic study. AB - Clinical records and radiographs of 90 patients with 113 anterior maxillary supernumerary teeth (mesiodens) have been evaluated. Although uncommon, mesiodentes are the most frequent supernumerary teeth and may disturb the eruption and/or position of the adjacent permanent incisors. Clinical and radiographic examination may disclose the number, direction and location of mesiodentes and their effects on neighbouring teeth. In the present study the majority of the supernumerary teeth lay palatal to the central incisors. Complete or partial eruption of a mesiodens was rare, hence the importance of radiographs to locate supernumerary teeth in the premaxilla. Pathological findings included the formation of dentigerous cysts in three patients and complete ossification of the pericoronal space with resorption of the crown of the mesiodentes in eight cases. Retention and malposition of the adjacent permanent incisors occurred in 39 and 24 cases, respectively. PMID- 1627068 TI - Restoration longevity in an Australian Defence Force population. AB - Replacement of restorations comprises a considerable portion of the work of most dentists. Consequently, factors that affect restoration longevity can influence the pattern of dental practice in a given community. Based on the results of research into treatment provision in the General Dental Service in Scotland, it was considered possible that factors such as the frequency with which patients were examined, and the frequency with which they changed dentists, might influence restoration longevity in other populations. Therefore, the present study was initiated to investigate the effects of these two factors in a population of 100 long-term members of the Royal Australian Air Force. No statistically significant relationship could be found between examination frequency, or frequent changes in dental practitioner, and restoration longevity. It is proposed that the large differences found in restoration longevity between this study and the Scottish study upon which it was based, may be due in part to the differing modes of remuneration of the dentists in the two studies. PMID- 1627069 TI - Dental caries amongst Royal Australian Navy recruits, 1988. AB - A sample of 1100 Royal Australian recruits were examined for dental caries in 1988. Socio-demographic data were also collected. The mean DMFT scores were 4.33, 6.85, and 8.87 teeth for the 15-19 year-olds, 20-24 year-olds, and 25-29 year olds, respectively. Caries experience varied between the state of origin of recruitment with Victorian and Queensland subjects having the highest DMFT scores, and Tasmanian subjects, the lowest. Comparison with previous military studies indicated not only a decreased dental caries experience, but also that restoration of teeth rather than extraction is a more likely treatment outcome of dental caries in recent recruits. PMID- 1627070 TI - Dental treatment and dental health. Part 2. An alternative philosophy and some new treatment modalities in operative dentistry. AB - In this, the second of two papers on the relationships between dental treatment and dental health, the philosophical basis of Minimum Intervention Dentistry is presented. This approach to patient care has several distinct treatment modalities. These range from preventive measures and fissure sealants, through monitoring carious lesions for active progression or arrest, to minimal cavity designs such as tunnel preparations and preventive resin restorations which employ adhesive dental restorative materials. This paper discusses these techniques and the implications of this change in philosophy for dental teaching, research and manpower considerations. PMID- 1627071 TI - Emigration tendencies among Hong Kong Chinese dentists--1990. AB - A postal questionnaire survey was conducted in April-May 1990 among 1223 Hong Kong Chinese dentists resident in Hong Kong to ascertain their plans for emigration from the Territory, as there were no data on emigration trends among dentists. A response rate of 47 per cent was obtained. Only 7 per cent of respondents definitely did not plan to emigrate and 47 per cent planned definitely or hopefully to emigrate, mostly in the years prior to 1997. Canada, Australia and the United States of America were the destinations most commonly cited by those planning to emigrate, and only one-quarter of these have any plans to return to Hong Kong. It was concluded that the emigration and return of Hong Kong dentists would influence workforce planning in the territory, and thus should be monitored. PMID- 1627072 TI - Survey of dental practice/dental education in Victoria. Part V. One-year follow up survey of 1988 graduating class. AB - A follow-up survey of the 1988 graduating class was carried out in order to compare views of the same cohort after 12 months of dental practice. The most significant finding was that there were few changes in opinion in respect to those subjects where 60 per cent or more respondents in the 1988 survey had judged the practical and/or theoretical components to have too little emphasis. These included fixed prosthodontics, occlusion, orthodontics, endodontics, aesthetic dentistry, oral surgery, conservative dentistry and care of the special patient. Recent changes to the undergraduate curriculum were high-lighted and the need for further development in continuing education courses was re-emphasized. PMID- 1627074 TI - Oral herpes remission and fluoride pulsing. PMID- 1627073 TI - Present and future patterns of practice and workforce needs in oral and maxillofacial surgery. AB - Oral and maxillofacial surgeons have shown curiosity and concern for their present and future patterns of practice and workforce needs. Few oral and maxillofacial surgeons would not have an understanding of how they came to be, or opinions on where the specialty is and appears to be going. Such opinions, however, need to be rigorously tested against the best available information. Quantitative information is the substantive input to decisions on whether oral and maxillofacial surgeons wish to go where they appear to be going, and if so why, and if not, why not? The Oral and Maxillofacial Surgeons 1990 Workforce Study* aimed to provide information relevant to these questions. Oral and maxillofacial surgeons are surprising in both their heterogeneity in patterns of practice and homogeneity in most of the content of services provided. Projections of the workforce indicate that a status quo in recruitment is actually a steady decline in capacity to serve the community, a picture in contrast to the international comparative data and opinion that supports a broadening in the service role of oral and maxillofacial surgeons. The Oral and Maxillofacial Surgeons 1990 Workforce Study offers insights into present and future patterns of practice and workforce needs. Ultimately, however, decision-making in the specialty will reflect additional social, economic and dento-political factors to which the Australian and New Zealand Association of Oral and Maxillo-Facial Surgeons must be the major contributor. PMID- 1627075 TI - Soft tissue sports injuries. First of a continuing series on sports medicine. PMID- 1627076 TI - Acute chest pain. AB - Of the many causes of acute chest pain, it is important to delineate the life threatening causes, such as myocardial infarction, dissecting aneurysm and pulmonary embolism. It is important to consider the cause as 'myocardial infarction until proved otherwise'. Common causes in general practice are musculoskeletal disorders and functional problems. A diagnostic strategy is outlined. PMID- 1627077 TI - Influenza surveillance in general practice. AB - This paper describes a survey of influenza conducted in general practice from July to October 1990. The study demonstrates how interested general practitioners can be involved in community based surveillance for the early detection of influenza outbreaks. PMID- 1627078 TI - Intra-articular injection of a finger. PMID- 1627079 TI - Patient education. Schizophrenia. PMID- 1627080 TI - Tuberculoid leprosy in country Victoria. Pitfalls in clinical diagnosis. PMID- 1627081 TI - The 'crown' excision for facial skin lesions. PMID- 1627082 TI - Half days of our lives. PMID- 1627083 TI - Radiotherapy and skin cancer. PMID- 1627084 TI - The management of common respiratory infections. PMID- 1627085 TI - Vaccine efficacy for reducing turbinate atrophy and improving growth rate in piggeries with endemic atrophic rhinitis. AB - Two vaccines, based on formalin-killed whole cells of toxigenic Pasteurella multocida type D and Bordetella bronchiseptica combined with a partially toxoided cell extract of P multocida, were prepared with Freund's incomplete adjuvant (vaccine 1) or by alum precipitation (vaccine 2). Each was tested for safety and efficacy in reducing the severity of nasal turbinate atrophy and improving the growth rate of pigs in three Western Australian commercial piggeries with endemic atrophic rhinitis. In safety experiments with vaccine 1, no adverse clinical effects were observed in vaccinated sows or their progeny. Piglets receiving vaccine 2 showed no injection site abnormalities, pyrexia or turbinate atrophy. In field trials, vaccine 1 significantly reduced the prevalence of moderate to severe nasal turbinate atrophy (Done score 3 to 5) when used in two piggeries (A and B). Progeny from vaccinated sows in piggery B also grew significantly faster than controls. When vaccine 2 was used in piggery A at a later date and in another piggery (C), growth rate was not improved in either piggery and the prevalence of moderate to severe turbinate atrophy was reduced only in piggery C. PMID- 1627086 TI - Cadmium concentrations in the kidneys of Western Australian pigs. PMID- 1627087 TI - Suspected Sarcocystis encephalitis in a stillborn kid. PMID- 1627088 TI - Lymphocystis in cultured snapper (Pagrus auratus) and wild kingfish (Seriola lalandi) in Australia. PMID- 1627089 TI - Suspected jute seed (Corchorus olitorius) poisoning of cattle. PMID- 1627090 TI - Serological evidence for the presence of Leptospira interrogans serovar bratislava in Australian pigs. PMID- 1627091 TI - High level resistance to cypermethrin in the sheep body louse. PMID- 1627092 TI - A comparison of the interferon gamma assay with the absorbed ELISA for the diagnosis of Johne's disease in cattle. PMID- 1627093 TI - Changes in hematological, blood gas, and serum biochemical variables in broilers during exposure to simulated high altitude. AB - One-day-old broilers were reared until 35 days of age at both natural low (100 m) and simulated high altitude (2133 m) to assess the incidence and development of ascites syndrome. Clinical measurements were conducted at 7, 14, 21, 28, and 35 days of age. Birds reared at 2133 meters exhibited significantly (P less than or equal to 0.05) reduced body weights at 7 through 28 days of age. Total serum calcium and biochemical enzyme activities were found to be altered at 35 days of age. In addition, the high-altitude group had significantly (P less than or equal to 0.05) higher erythrocyte counts, hematocrits, and hemoglobin at 14, 21, 28, and 35 days of age and higher serum inorganic phosphorus at each weekly sample time than birds at the low altitude. Total mortality was 20.3% at 2133 meters and 4.6% at 100 meters. The incidence of ascites syndrome in the high-altitude group ranged from 16.6% to 61.1% during the 5-week experimental period. PMID- 1627094 TI - Colonization of Escherichia coli in young turkeys and chickens. AB - In order to investigate the possibility of pathogenic Escherichia coli penetrating the bloodstream via the intestinal mucosa in normal and stressed turkeys and chickens, birds were inoculated orally with the bacteria or exposed environmentally to it. Immediately after hatch, intestines contained a substantial number of coliform bacteria that increased with time. In orally infected turkeys, the pathogenic bacteria (nalidixic-acid-resistant O78) replaced 10%-50% of the native coliform flora but could not be isolated from the trachea or blood. Environmentally exposed groups exhibited pathogenic bacteria in intestines but not in blood. Stressing of exposed turkeys resulted in isolation of the pathogenic bacteria from blood and even spleen. In orally infected broiler chickens, stress resulted in bacteremia and mortality. Chickens that were exposed to pathogenic bacteria at a young age and showed no mortality or morbidity demonstrated no detrimental effects due to challenge with the same pathogenic bacteria later in life. Stress seems to cause penetration of the pathogenic bacteria into the bloodstream, which in turn can cause severe disease and mortality. PMID- 1627095 TI - Comparison of a vaccine strain and field isolates of avian reovirus by T1 oligonucleotide mapping. AB - Total RNA of eight avian reovirus isolates and the S1133 strain were compared by RNase T1-oligonucleotide mapping. The viruses were propagated in Vero cell cultures, and viral genomes were extracted from purified virions for comparison. Pairwise comparisons of the oligonucleotide maps showed genetic variation among reovirus isolates ranging from 78% to 99%. The T1 fingerprints of the RNA of isolates 1103, 724, 615, and 684 differed slightly from the standard S1133 strain, suggesting that the vaccine strain might have changed and became part of the circulating reoviruses. In contrast, when compared with the vaccine strain, isolates 902, 644, and 6207 showed greater differences in the fingerprint pattern. This genomic diversity may be due to the differences in immunological status of the affected avian population and/or due to simultaneous coinfection with different reovirus strains. PMID- 1627096 TI - Frequency of Salmonella enteritidis and other salmonellae in the ceca of spent hens at time of slaughter. AB - A study was conducted to determine the frequency of Salmonella enteritidis (SE) and other Salmonella serovars in the cecal contents of spent laying hens at a hen processing plant in the southeastern United States over a 4 1/2-month period, from October 1990 through February 1991. A total of 1920 pooled cecal samples (three ceca per sample) from 38 flocks representing 23 producers were obtained and tested for the presence of SE and other Salmonella serovars. A total of 359 samples (18.7%) from 37 of the 38 flocks (97.4%) showed characteristic reactions for salmonellae on triple sugar iron agar (TSIA) slants. Twenty-nine of the 359 Salmonella-positive samples (8.1%) were Group D-positive, all of which were found to be SE on further serotyping. The SE-positive samples were from seven of the 38 flocks (18.4%); four flocks originated from the USDA/APHIS-designated Northern Region of the United States, and three were from the Southeastern Region. Serotyping of the 330 TSIA-positive Group-D negative Salmonella revealed 37 different serovars. S. heidelberg, the predominant serovar, was identified in 49.1% of these isolates. PMID- 1627097 TI - Prevalence of Salmonella enteritidis in spent hens. AB - As part of a USDA/APHIS study on the prevalence of Salmonella enteritidis in spent laying hens, 3700 pooled cecal samples were cultured for Salmonella. Samples were received from a single processing plant and represented 81 commercial egg-type layer flocks from nine southern states. Salmonella were isolated from 2418 of the 3700 (65.4%) cecal pools, but only six isolates were serotype enteritidis. S. enteritidis was isolated from three flocks from two states but was detected in only six of 140 samples from those flocks. Various Salmonella isolation media and procedures were compared. Xylose-lysine-tergitol-4 plates detected 64% of the total Salmonella-positive cecal samples. Brilliant green agar with novobiocin detected 72% of the total Salmonella-positive samples. When used in combination, 82% of the positive samples were detected with these two plates. The remaining 425 Salmonella-positive samples were detected after delayed secondary enrichment. PMID- 1627098 TI - Transmission of Pasteurella multocida on California turkey premises in 1988-89. AB - Restriction endonuclease analysis (REA) of whole-cell DNA was used to determine possible sources of Pasteurella multocida for each outbreak of fowl cholera occurring in turkey flocks in eight commercial poultry companies in California from October 1988 to September 1989. Over this period, 179 isolates of P. multocida were obtained from dead turkeys in 80 meat and breeder flocks on 43 premises. P. multocida was isolated from wildlife on five premises. Isolates were characterized by subspecies, serotype, presence of plasmid DNA, and REA type. In 52 (65%) flocks, all isolates of P. multocida had the same REA pattern as the M9 live vaccine strain following digestion of DNA with the restriction enzyme SmaI. Field strains of P. multocida were obtained from 27 (34%) flocks, and one flock (1%) yielded both M9 and a field strain of the organism. REA of field strains of P. multocida revealed 17 different SmaI REA types. Based on matching SmaI REA types, potential sources of P. multocida were identified for 15 of the 28 flocks infected with field strains of the organism, and transmission between turkey premises was a possibility in only seven flocks. PMID- 1627099 TI - Restriction endonuclease analysis of Pasteurella multocida isolates from three California turkey premises. AB - Three California turkey premises that had repeated outbreaks of fowl cholera were studied for periods of 2 to 4 years. Using biochemical, serologic, plasmid DNA, and restriction endonuclease analyses of isolates of Pasteurella multocida from turkeys and wildlife on the premises, strains of the organism were found to be enzootic on two of the premises. On the third, a variety of strains of P. multocida were isolated from fowl cholera outbreak flocks. PMID- 1627100 TI - Necrotizing typhlocolitis associated with a spirochete in rheas (Rhea americana). AB - Necrotizing typhlocolitis was diagnosed in 13 juvenile common rheas (Rhea americana) from three separate of geographically isolated Ohio flocks, with mortality ranging from 25% to 80%. At postmortem examination, a diphtheritic membrane covered ulcerated cecal mucosa. Histologically, cecal sections showed necrosis and granulomatous-to-suppurative inflammation that extended into the submucosa and often surrounded large eosinophilic colonies of bacteria. Warthin Starry staining showed these colonies to be composed of entangled spirochetes that invaded the submucosa and frequently were present transmurally. Similar organisms were identified by Warthin-Starry staining in the cecum of a juvenile rhea from a fourth flock that histologically had mild lymphocytic typhlitis. Scanning and transmission electron microscopy demonstrated the presence of a spirochete in the ceca. Anaerobic culture yielded a gram-negative, beta-hemolytic spirochete. Coccidia, histomonads, and Salmonella spp. were consistently absent. PMID- 1627101 TI - Spondylitis in turkeys associated with experimental Pasteurella anatipestifer infection. AB - Nine previously vaccinated turkeys were inoculated intravenously with Pasteurella anatipestifer, and blood samples were taken periodically to evaluate the potential of chronically infected turkeys to serve as reservoirs of infection for blood-feeding arthropod vectors. Vertebral osteomyelitis (spondylitis), as yet unreported in the literature in association with infection with the organism, was found in the thoracic vertebrae of five out of nine inoculated turkeys, and P. anatipestifer was isolated from the thoracic vertebrae of three of the five. The organism was isolated from the peripheral blood of six turkeys 24 hours postinoculation and from the peripheral blood of one turkey 7 days postinoculation. The organism was also isolated from the heart blood of two birds at necropsy--from one at 21 days and, following an intramuscular injection of dexamethasone, from the other turkey at 38 days postinoculation. PMID- 1627103 TI - Pathogenicity of Salmonella pullorum in northern bobwhite quail and mallard ducks. AB - Ten-day-old northern bobwhite quail and mallard ducks were inoculated orally and intravenously with Salmonella pullorum at selected concentrations (10(3) to 10(10) colony-forming units). Mortality in bobwhites ranged from 65% to 100%, whereas no mallards died or exhibited any signs of morbidity. Significantly (P less than 0.05) increased values for serum calcium, uric acid, and lactate dehydrogenase were observed in mallards inoculated with live S. pullorum, and antibody titers were detected as early as 1 week postinoculation. Viable bacteria were cultured from feces, liver, lungs, heart, kidneys, pancreas, and spleen of bobwhites and from livers of four mallards. Bacterial colonies were frequently found in the capillaries of various organs of the quail, particularly in the heart and kidneys, with slight-to-moderate diffuse or multifocal necrotizing inflammation present in all organs examined. Bobwhites are susceptible to infection from S. pullorum, with morbidity and mortality rates similar to those of chicks and poults, whereas mallards undergo a short, subclinical infection that is resolved without lasting tissue damage. PMID- 1627102 TI - Binding of Salmonella strains to immobilized intestinal mucosal preparations from broiler chickens. AB - The binding kinetics of radiolabeled Salmonella california 1989/O (mannose sensitive hemagglutinin-positive [MSHA+]) to immobilized mucus or enterocytes isolated from broiler ceca and inhibition of binding by D-mannose and sodium metaperiodate were characteristic of adherence of mannose-sensitive type 1 fimbriae of bacteria to eukaryotic mannose-containing receptors. Binding by radiolabeled strains 1989/O (in the presence of D-mannose) and S. typhimurium S 7471 N (MSHA-, non-fimbriated) indicated non-specific binding that was characterized by less binding to enterocytes and mucus and lack of inhibition by carbohydrates or prior treatment with sodium metaperiodate. Inhibition of non specific binding to enterocytes by pretreatment with various enzymes or by the presence of tetramethylurea or p-nitrophenol (known to disrupt hydrophobic interactions) indicate involvement of multiple sites and hydrophobic bonding. Strain-specific outer-membrane preparations inhibited non-specific binding to a greater extent than did lipopolysaccharide, Escherichia coli outer-membrane preparations, or bovine serum albumin. PMID- 1627104 TI - Pathological study of lead poisoning in whooper swans (Cygnus cygnus) in Japan. AB - During spring 1989, thirty-three whooper swans (Cygnus cygnus) died at Lake Miyajima in Hokkaido, Japan; 15 were examined. The birds were diagnosed as having subacute lead poisoning due to ingestion of spent lead shot. The main gross findings were bile-stained liver, edematous or gelatinous bone marrow, bile stained lining with hyperkeratosis and lead pellets in the gizzard, and proventricular impaction. Histopathologically, there was lead-hemolytic jaundice of the liver, hemosiderosis in the liver and spleen, and hypoplasia of the bone marrow with increased numbers of polychromatic erythroblasts. Acid-fast intranuclear inclusion bodies were seen in kidneys of seven swans. Under electron microscopy, inclusion bodies had frayed contours and consisted of high-electron dense fine granules. The lead concentration of the liver ranged from 5.5 to 44.3 mg/kg wet weight. It was suggested that these changes resulted from excess breakdown of erythrocytes, inhibition of heme synthesis, and impaired erythropoiesis caused by lead shot. PMID- 1627105 TI - Molecular characterization of Salmonella enteritidis isolates from Maine poultry and poultry farm environments. AB - Eighty-six Salmonella enteritidis isolates obtained during a surveillance program of poultry farms in Maine were subjected to phage-typing, plasmid profiling and fingerprinting, outer-membrane polypeptide analysis, and antimicrobial sensitivity testing. Isolates were obtained from a variety of sources, including poultry-farm environmental samples, chicken organ samples, human stool samples, cat feces, and live-trapped rats and mice. These isolates were compared with 21 S. enteritidis isolates originating outside of Maine. Phage types isolated in Maine included 13a (60%); 14b (29%); 23 (5%); 8 (2%); and 2 (2%). All S. enteritidis isolates from Maine carried plasmid DNA, and 97% of these isolates carried a 40.3-megadalton plasmid alone (6%) or in conjunction with several smaller plasmids (91%). All 52 phage-type 13a isolates harbored 40.3- and 3.0 megadalton plasmids. All 25 phage-type 14b isolates carried 3.3- and 1.3 megadalton plasmids, and 22 isolates also carried the 40.3-megadalton plasmid. All isolates displayed highly similar outer-membrane polypeptide profiles and were sensitive to a variety of antimicrobials commonly used against gram-negative organisms. The above data suggest that phage type and plasmid content may be related in the cases of phage-type 13a and 14b isolates, and that traditional plasmid-borne antimicrobial resistance determinants were not present in Maine isolates. Results also indicate that phage-typing can be a valuable epizootiological tool for monitoring the potential spread of these strains throughout the Northeast. PMID- 1627106 TI - Effect of nitrofurazone or novobiocin on Salmonella enteritidis cecal colonization and organ invasion in Leghorn hens. AB - Nitrofurazone (433 mg/liter drinking water) administration to leghorn laying hens for 72 hours with a 48-hour withdrawal period before nitrofurazone-sensitive Salmonella enteritidis challenge resulted in a S. enteritidis culture-positive rate significantly (P less than 0.05) higher than that of unmedicated controls when hens were cultured 6 days following challenge. In a similar experiment, simultaneous nitrofurazone administration and S. enteritidis challenge resulted in no significant differences in S. enteritidis isolation frequency. However, unchallenged nitrofurazone-medicated contact control hens showed a significantly higher S. enteritidis culture-positive rate than the unchallenged unmedicated controls. This increase in apparent S. enteritidis susceptibility was associated with significantly lower cecal propionic acid and fewer anaerobic colony-forming units (CFU). In a third experiment, nitrofurazone treatment had no effect when the antibiotic was withdrawn 72 hours before S. enteritidis challenge. In a subsequent experiment, novobiocin (385 mg/kg) or nitrofurazone (300 mg/kg) was administered to adult hens for 7 days before challenge with nitrofurazone and novobiocin-resistant S. enteritidis. Both nitrofurazone and novobiocin administration resulted in a significantly higher S. enteritidis culture-positive rate than unmedicated controls at end of the experiment 7 days post-challenge. Results indicate that administration of some antibiotics may enhance susceptibility to S. enteritidis in leghorn hens. PMID- 1627107 TI - Characteristics of conjugative R-plasmids from pathogenic avian Escherichia coli. AB - Three of four virulent avian Escherichia coli isolates transferred a single large molecular-weight R-plasmid to two recipient E. coli strains. Antibiotic resistances transferred included streptomycin (two isolates) and streptomycin tetracycline-sulfa (one isolate). Production of colicin and siderophores, complement resistance, and embryo lethality present in the virulent isolates were not transferred to recipient organisms. From the results, it appears that the R plasmids of these virulent avian E. coli are not associated with virulence. PMID- 1627108 TI - Inability of so-called chicken anemia agent (CAA) infections to be diagnosed by anemia and hematopoietic organ atrophy alone. AB - In the recent past, anatomic and clinical pathologic diagnoses of so-called chicken anemia agent (CAA) infections have been based on lesions such as anemia and hematopietic organ atrophy (HOA). In the present study, significant (P less than or equal to 0.05) positive and negative correlations were seen in a lesion matrix constructed from 89 cases of anemia and HOA in Georgia broilers during 1988 and 1989. Only splenic atrophy and bursal atrophy were not significantly associated. We concluded that information regarding only HOA and anemia is not sufficient to allow pathologists to diagnose CAA in broiler chickens submitted to diagnostic laboratories such as ours. PMID- 1627109 TI - Pathogenicity of Campylobacter jejuni for turkeys and chickens. AB - A Campylobacter jejuni isolate obtained from a turkey liver, designated C101, and a C. jejuni isolate obtained from the feces of a chicken, designated C111, were used to inoculate their respective hosts. Isolate C101 depressed weight gain by 20% when inoculated into newly hatched poults or 4-day-old poults. It also caused death, hepatic necrosis, and generalized hemorrhages in turkey embryos. The chicken-derived isolate, C111, did not reduce weight gain in newly hatched chicks, but it did induce mortality in chicken embryos. The supernatant of the cultures of both C. jejuni isolates also caused mortality in embryos. PMID- 1627110 TI - Optimum conditions for the turkey lymphocyte transformation test. AB - Optimum conditions for turkey lymphocyte transformation tests were determined. Thrice-washed turkey buffy-coat cells obtained after slow centrifugation (40 x g, 10 minutes) responded well to mitogenic stimulation. Turkey lymphocytes isolated on Ficoll-containing separation media largely lost their ability to respond to mitogens. Maximum responses were obtained with 2 x 10(7) lymphoid cells/ml. Responses to the mitogens were greatest when bovine fetal serum was used at a 2.5% concentration or pooled turkey serum and autologous plasma were used at a 1.25% concentration. Higher concentrations of turkey serum or plasma decreased the responses when sub-optimum doses of concanavalin-A (Con A) or phytohemagglutinin-P (PHA-P) were used. Serum-free cultures gave higher stimulation indices than cultures with serum only when sub-optimum doses of Con A or PHA-P were used. Optimum mitogen concentrations varied with individual birds, timing of the culture, temperature of incubation, and serum concentration in the cultures. Responses were usually greatest with final concentrations of 5 micrograms Con A/ml, 10 micrograms PHA-P/ml, and 20 micrograms pokeweed mitogen (PWM)/ml and when the cultures were incubated in 96-well microplates at 40 C in humidified air with 5% CO2 for 40-42 hours with pulsing with 3H-thymidine during the final 16 hours of incubation. PMID- 1627111 TI - Comparison of a complement resistance test, a chicken embryo lethality test, and the chicken lethality test for determining virulence of avian Escherichia coli. AB - Results with four pathogenic avian Escherichia coli isolates and one avirulent isolate in a complement resistance test, a chicken lethality test, and a chicken embryo lethality test were compared. Results of the complement resistance test with these isolates were highly correlated to results of the chicken lethality test of virulence. The chicken embryo test yielded results that were of a medium positive correlation with the chicken lethality results. The results of the complement resistance and chicken embryo lethality tests were highly correlated. PMID- 1627112 TI - Vaccination of turkeys with cell-free culture filtrate of Pasteurella multocida: effects of ultrafiltration and endotoxin removal. AB - Cell-free culture filtrate (CCF) of Pasteurella multocida strain R44/6 (serotype 3/4/9/12) was fractionated by ultrafiltration into fractions of less than 10,000, greater than 10,000, greater than 30,000, and 10,000 to 30,000 molecular weight (MW). The less-than-10,000-MW fraction contained little endotoxin comparable to bacteriologic medium; the 10,000-to-30,000-MW fraction had a moderate amount of endotoxin, whereas the greater-than-10,000- and greater-than-30,000-MW fractions contained high levels of endotoxin. Following ultrafiltration, each fraction, except the less-than-10,000-MW fraction, was divided into two equal parts, and endotoxin was removed from one part. Turkeys were vaccinated with the various MW fractions of CCF, with and without endotoxin, via the air sacs at 6 and 9 weeks of age and compared with negative controls given bacteriologic medium and positive controls vaccinated with a commercial bacterin. Before oral challenge with strain P-1059 (serotype 3) at 12 weeks of age, antibody titers were detected only in positive control turkeys. Protection against challenge, as measured by post-challenge mortality and body-weight gain, was provided by the greater-than 10,000-, greater-than-30,000-, and 10,000-to-30,000-MW fractions containing endotoxin and the commercial bacterin. Turkeys that had been vaccinated with bacteriologic medium and the four different fractions without endotoxin were not protected. Results indicated that endotoxin in CCF of P. multocida is critical in protecting turkeys from pasteurellosis. PMID- 1627113 TI - Packed cell volume reference intervals to aid in the diagnosis of anemia and polycythemia in young broiler chickens. AB - Packed cell volume (PCV) reference intervals were established for use in diagnosing anemia and polycythemia in young broiler chickens. Blood samples were collected from one hundred twenty 3-to-49-day-old clinically healthy conventionally reared broiler chickens. PCVs were determined and analyzed. PCVs regressed significantly (P less than 0.025) on age, which shows that neonatal physiologic anemia occurs in broiler chickens, as well as in mammals and specific pathogen-free (SPF) chickens. The definition for anemia in broiler chicks varies with age. We defined anemia as a PCV less than or equal to 26%, 29%, 33%, 32%, 33%, 33%, 31%, and 28% for broiler chickens, 3, 7, 14, 21, 28, 35, 42, and 49 days old, respectively. We define polycythemia as a PCV greater than or equal to 42%, 43%, 41%, 40%, 42%, 42%, 41%, and 40% for broiler chickens 3, 7, 14, 21, 28, 35, 42, and 49 days old, respectively. Otherwise, broiler chickens have PCVs within established reference intervals. Results provide guidelines for detecting anemia and polycythemia in young broiler chickens of various ages. PMID- 1627114 TI - Toxicological pathology of cockleburs (Xanthium spp.) for broiler chickens. AB - Spiking mortality syndrome (SMS) in chickens resembles cocklebur toxicity in cattle, sheep, pigs, and rats. In order to determine if cockleburs are toxic to broiler chicks, crushed burs were fed (25% wt:wt) to broilers for 21 days. Ingestion of cockleburs resulted in significant failure to properly gain body weight. Otherwise, chicks did not develop clinical signs of illness or gross or microscopic lesions. Although there were some significant differences in serum chemistry values among chick groups, there were no consistent patterns. Severe hypoglycemia is said to be a characteristic finding in chicks that die with SMS. Because glucose levels were not low in chicks that were fed cockleburs, we feel certain that cockleburs do not cause SMS. PMID- 1627116 TI - Fumonisin mycotoxicosis in broilers: performance and pathology. AB - Fusarium moniliforme culture material containing fumonisin B1 at 300 mg/kg was incorporated into a broiler starter ration and fed ad libitum to 1-day-old broiler chicks for 2 weeks in two experiments. Clinical features of the disease produced included diarrhea, a 19% reduction in body weight, a 30% increase in relative liver weight, and a worsening of feed conversion by 20 points at 2 weeks of age. Histologically, chicks fed fumonisin had multifocal hepatic necrosis, biliary hyperplasia, muscle necrosis, intestinal goblet-cell hyperplasia, and rickets. Simultaneous feeding of 0.5% aluminosilicate had no effect on the clinical disease or lesions. The clinical disease and lesions induced mimicked those of a viral enteritis. PMID- 1627115 TI - Use of the fluorochromes xylenol orange, calcein green, and tetracycline to document bone deposition and remodeling in healing fractures in chickens. AB - The fluorescent calcium binding dyes xylenol orange, calcein green, and tetracycline were used successfully to sequentially label new bone deposition and bone remodeling during the healing of rigidly fixed humeral fractures in the chicken. Xylenol orange and calcein green, administered subcutaneously at 90 mg/kg and 10 mg/kg, respectively, provided easily identified and differentiated bands in newly deposited bone within periosteal and endosteal calluses, intercortical gaps, and screw holes. Tetracycline, administered at 50 mg/kg per os by crop tube, labeled bone faintly in a non-specific manner. Parenteral administration of the same compound might have yielded better results. PMID- 1627117 TI - Cloacal flora isolated from wild black-bellied whistling ducks (Dendrocygna autumnalis) in Laguna La Nacha, Mexico. AB - Cloacal swabs from 110 adult black-bellied whistling ducks trapped at Laguna La Nacha, Tamaulipas, Mexico, were cultured to determine the prevalence of normal and potentially pathogenic bacteria. Twenty-five gram-negative enterobacteria and four gram-positive cocci were isolated. The most common isolates included Escherichia coli (54%), Staphylococcus spp. (29%), Streptococcus spp. (22%), Aeromonas hydrophila (15%) Enterobacter cloacae (14%), and Micrococcus sp. (14%). The implications of whistling ducks as possible reservoirs of pathogenic bacteria are discussed. PMID- 1627118 TI - High mortality of domestic turkeys associated with Ascaridia dissimilis. AB - Third- and fourth-stage Ascaridia dissimilis larvae were isolated from commercial white turkey intestinal scrapings from two farms that were experiencing high mortality. Lesions consisted of a necrotic-like enteritis that was most severe in the jejunum. Subsequent bacteriological isolation yielded heavy growth of Escherichia coli and Clostridium perfringens. The rate of mortality declined rapidly when the turkeys were administered 18 ppm fenbendazole for 7 days. PMID- 1627119 TI - Squamous-cell carcinoma on the legs of an Aracauna chicken. AB - Squamous-cell carcinoma was diagnosed on both legs of a 6-year-old pet Aracauna chicken. Grossly, the tumors were raised and horny with superficial ulceration. Histologically, the tumors were highly invasive, extending deep into the dermis, tendon sheaths, and periosteal tissues. There was no evidence of vascular invasion or metastasis to other organs. PMID- 1627120 TI - Doxycycline plasma concentrations in macaws fed a medicate corn diet. AB - A trial was conducted to determine the doxycycline plasma concentrations attained by feeding a medicated corn diet to large psittacine birds. Doxycycline is the preferred drug for the treatment of chlamydiosis in psittacine birds. Healthy macaws were fed a 0.1% doxycycline-medicated corn diet for 45 days, and plasma doxycycline concentrations were determined by microbiological assay on treatment days 3, 15, 30, and 45. Plasma doxycycline concentrations exceeded 1 microgram/ml in 87% of the samples assayed. As blood concentrations of 1 microgram/ml are considered therapeutic, a doxycycline-medicated corn diet may be efficacious in the treatment of chlamydiosis in large psittacine birds. PMID- 1627121 TI - Description of a microfilaria from an umbrella cockatoo (Cacatua alba) and an unsuccessful attempt to infect mosquitoes (Culex pipiens pipiens). AB - Unidentified microfilariae circulating in the blood of an umbrella cockatoo (Cacatua alba) are described. They are ensheathed, measure 102-152 microns long and 2-3 microns in diameter, and have four distinct and consistent gaps in the nuclear column. Attempts to infect mosquitoes (Culex pipiens pipiens) with the microfilariae were unsuccessful. PMID- 1627122 TI - Thermal biofeedback treatment of mild hypertension. A comparison of effects on conventional and ambulatory blood pressure measures. AB - Several studies have produced results suggesting that thermal biofeedback treatment is effective in lowering the blood pressure (BP) of individuals with both mild and moderate essential hypertension. This study used thermal biofeedback to treat 9 unmedicated individuals with mild hypertension. Subjects underwent 24-hour ambulatory BP monitoring both prior to and following the thermal biofeedback treatment regimen. Four of the subjects were considered treatment successes using standard office blood pressure assessments as the success-fail criteria. However, 24-hour ambulatory BP measures showed a markedly different pattern of results, with several subjects who were considered successes under conventional assessment techniques showing an increase in 24-hour ambulatory BP from pre- to posttreatment. There was a significant decrease in diastolic blood pressure for all subjects as measured by the ambulatory method. There was also a significant decrease in systolic and diastolic standing home blood pressure. The implications of these results are discussed. PMID- 1627123 TI - Development of the feminine gender role stress scale. A cognitive-behavioral measure of stress, appraisal, and coping for women. AB - The cognitive appraisal of threats and challenges to sterotypical feminine gender role coping behavior was defined as feminine gender role stress (FGRS). This article describes the development of a self-report measure of FGRS. Situations perceived as more stressful for women than for men wer categorized by factor analysis, yielding the following constellation of maladaptive stress responses particularly salient for women: (a) fear of unemotional relationships, (b) fear of being unattractive, (c) fear of victimization, (d) fear of behaving assertively, and (e) fear of not being nurturant. Women demonstrated significantly higher FGRS appraisal scores than men, and scores among women showed good 2-week test-retest reliability. The tendency to appraise situations on the FGRS scale as stressful was associated with the tendency to consider daily hassles stressful but was not related to self-perceived femininity in women. It was predicted that women who tend to exhibit the FGRS appraisal style would have more difficulty in coping with stressors related to depression. Supporting this hypothesis, women with higher FGRS scores reported greater depression than those with lower scores. The assessment of FGRS appraisal and coping style in women provides useful information for devising treatment strategies to improve women's health through promotion of adaptive coping. PMID- 1627124 TI - Proteolytic processing of amyloid beta protein precursor (APP) by thrombin. AB - Search for proteases responsible for an altered processing of APP which generates intermediates containing beta/A4 peptide is preceding to understand the formation of beta amyloid deposits characteristic of Alzheimer's disease, since many studies reveal that APP is ordinarily processed so as not to generate beta amyloid. Here, we have examined the action of thrombin, a serine protease in the blood clotting, in APP processing. Thrombin cleaved the mouse recombinant APP695 in vitro, resulting in the accumulation of 28 kDa fragment. The immunoblot analysis showed that the fragment is derived from the carboxy-terminal side of the recombinant APP695. Further, amino acid sequencing exhibited that the fragment is generated by the cleavage at Arg 510-Ile 511 and therefore includes entire beta/A4 peptide. We consider that the 28 kDa fragment is a possible intermediate for beta/A4 peptide. Thus thrombin may be involved in the altered processing of APP. PMID- 1627125 TI - Variable tRNA content in HIV-1IIIB. AB - Low molecular weight RNA in HIV-1 is found in three size classes resembling 7S RNA, 5S RNA, and tRNA. The 2-dimensional polyacrylamide gel electrophoresis (2D PAGE) patterns of tRNA found in HIV-1 have been determined in virus produced in five different cell types: H9, UHC1 (a U937-derived clone), UHC8 (an RT(-) derivative of U937), HeLa, and COS. The presence of the putative primer tRNA for reverse transcriptase, tRNA(Lys,3), has also been determined either by hybridization with a tRNA(Lys,3)-specific DNA probe or by a comparison of the electrophoretic mobility of viral tRNA species with purified human tRNA(Lys,3). Our results indicate the following: 1) The number of tRNA species found in infectious HIV-1IIIB produced in different cell types varies, according to cell type, from greater than 20 to 4, indicating that only 4 or less tRNA species are required for the viral infectious life cycle. 2) There are 1-3 tRNA species tightly associated to the viral genomic RNA, depending upon the cell type producing the virus. 3) The putative primer tRNA, tRNA(Lys,3), is detected with the tRNA(Lys,3)-specific hybridization probe in the tRNA of HIV-1 produced in H9 cells, and the tightly associated tRNA species in this virus has the same electrophoretic mobility in 1-D PAGE as purified tRNA(Lys,3). On the other hand, we cannot detect tRNA(Lys,3) in the tRNA of HIV-1 produced in HeLa cells, and the tightly associated tRNA found in this virus does not migrate with the same electrophoretic mobility as tRNA(Lys,3). PMID- 1627127 TI - Association of the carboxy-terminus of beta-amyloid protein precursor with Alzheimer paired helical filaments. AB - We investigated whether a peptide fragment from the C-terminus of beta-amyloid protein precursor is associated with Alzheimer paired helical filaments (PHFs). Antiserum BR188, to the last 20 amino acids of the precursor, did not cross-react with tau protein, known to be in PHFs. It did react with all five pronase-treated PHF preparations assayed by ELISA and immunogold-labelled the same PHF fibrils that a PHF-specific tau antibody labelled. Neither antibody labelled beta/A4 fibrils. These results suggest that a fragment from the C-terminus of beta amyloid precursor protein copurifies with pronase-treated PHFs and may play a role in their molecular pathogenesis. PMID- 1627126 TI - Inhibition of Ca(2+)-dependent catecholamine release by myosin light chain kinase inhibitor, wortmannin, in adrenal chromaffin cells. AB - To elucidate the possible involvement of myosin light chain kinase (MLCK) in the mechanism of exocytosis, we studied effects of MLCK inhibitor, wortmannin, on the secretory function of bovine adrenal chromaffin cells. Preincubation of chromaffin cells with wortmannin inhibited both acetylcholine- and high K(+) evoked catecholamine (CA) release. The IC50 for high K(+)-evoked CA release was 1 microM. When the cells were permeabilized with digitonin after wortmannin preincubation, Ca(2+)-dependent exocytosis was inhibited in a dose-dependent manner (IC50, 1 microM). These findings suggest the implication of MLCK in the Ca(2+)-triggered process in the machinery of exocytosis. PMID- 1627128 TI - Gene expression of metalloproteinase and its inhibitor in mesangial cells exposed to high glucose. AB - To clarify the roles of metalloproteinases and their inhibitor (TIMP) in diabetic glomerulopathy, we studied the effect of a high glucose concentration on the gene expression of metalloproteinase transin and TIMP as well as collagen type IV and laminin in cultured rat mesangial cells (MCs). In the high glucose group, collagen type IV, laminin, and TIMP mRNA levels were all elevated in a concentration-dependent manner, whereas transin expression was suppressed. Osmotic control of high glucose with mannitol selectively stimulated TIMP expression. We hypothesize that high glucose decreases matrix-degrading activity as well as increases matrix productivity in MCs. PMID- 1627129 TI - Nonspecific primer and PCR generated hybridization probes for physical ordering large restriction fragments in complex genome of S. aureus. AB - Pulsed field gel electrophoresis (PFGE) allows separation of large restriction fragments from bacterial genome. Restriction fragments obtained by digestion of Staphylococcus aureus DNA with rare cutting enzymes (Sma I, and Csp I) were separated by PFGE. To arrange the physical order of the fragments generated by digestion with one enzyme, probes were prepared by nonspecific priming and polymerase chain reaction (PCR), using individual fragments of the other enzymatic digest as a template. Probes were then used for Southern hybridization to the PFGE separated fragment distribution of the two infrequent cleaving enzymes (Sma I and Csp I). Using probes generated from four Sma I fragments and five Csp I fragments as individual templates, a partial physical order of Csp I fragments of the genome of S. aureus ISP8 has been determined in relation to a previously published Sma I map of S. aureus genome. PMID- 1627130 TI - Evidence for the involvement of tryptophan 38 in the active site of glutathione S transferase P. AB - Glutathione S-transferase P (GST-P) exists as a homodimeric form and has two tryptophan residues, Trp28 and Trp38, in each subunit. In order to elucidate the role of the two tryptophan residues in catalytic function, we examined intrinsic fluorescence of tryptophan residues and effect of chemical modification by N bromosuccinimide (NBS). The quenching of intrinsic fluorescence was observed by the addition of S-hexylglutathione, a substrate analogue, and the enzymatic activity was totally lost when single tryptophan residue was oxidized by NBS. To identify which tryptophan residue is involved in the catalytic function, each tryptophan was changed to histidine by site-directed mutagenesis. Trp28His GST-P mutant enzyme showed a comparable enzymatic activity with that of the wild type one. Trp38His mutant neither was bound to S-hexylglutathione-linked Sepharose nor exhibited any GST activity. These findings indicate that Trp38 is important for the catalytic function and substrate binding of GST-P. PMID- 1627131 TI - The phosphate groups of the high mobility group like protein P1 strengthens its affinity for DNA. AB - PCA soluble proteins isolated from rat liver and proliferating HeLa interphase cells were subjected to chromatography on columns containing immobilized s.s and d.s. DNA. P1 from rat liver was eluted from s.s. and d.s. DNA between 0.20 and 0.45 M NaCl, while dephosphorylated P1 was not retained by s.s. and d.s. DNA columns at 0.25 M, suggesting that phosphate groups enhance the affinity of P1 for DNA. P1 from proliferating HeLa interphase cells exhibit increased affinity for d.s. as well as s.s. DNA when compared to rat liver P1. The higher extent of phosphorylation in proliferating cells supports the finding that phosphate enhances rather than reduces the affinity of P1 for DNA. PMID- 1627133 TI - Procalpain I in cytoplasm is translocated onto plasma and granule membranes during platelet stimulation with thrombin and then activated on the membranes. AB - Thrombin stimulation of platelets resulted in changes in the subcellular localization of calpain I, with a concomitant alteration of its molecular weight as measured by immunoblotting. Calpain I in resting platelets was distributed as procalpain I, an 80 kDa form which does not exhibit the enzyme activity, and 83% of the total antigen was localized in the cytosol fraction. When platelets were stimulated with thrombin, the total content of calpain I antigen was not significantly changed as compared with that of the resting platelets, though a decrease in the cytosolic distribution of 80 kDa form (from 83% to 47% of the total antigen) was observed with concomitant appearance of the active 76 kDa and intermediate 78 kDa forms of calpain I and increase in the 80 kDa form in the granule and membrane fractions. These results indicated that calpain I was translocated from the cytosol to both the plasma and granule membranes as procalpain I and then activated on the membranes during platelet stimulation with thrombin. PMID- 1627132 TI - Metal-inducible activities of metallothionein promoters in fish cells and fry. AB - Activities of trout metallothionein-A promoter and mouse metallothionein-I promoter in fish cells and fry were examined using the chloramphenicol acetyltransferase (CAT) gene as a reporter. Transfection and transient CAT assays on a trout liver cell line indicated that both promoters were inducible by metals, including zinc. In vivo activities of both promoters were examined using microinjection system into medaka eggs. Some of the hatched fry were exposed to zinc and their CAT activities were assayed. Both promoters revealed considerable activities after exposure to zinc while only weak activities were detected in unexposed fry. PMID- 1627134 TI - Protein-tyrosine kinase p72syk is activated by wheat germ agglutinin in platelets. AB - We previously reported a molecular cloning of porcine gene syk encoding a non receptor type 72-kDa protein-tyrosine kinase (Taniguchi et al. (1991) J. Biol. Chem. 266, 15790-15796). In this study, we have demonstrated that p72syk is expressed in porcine platelets at 0.1-0.2% of total protein and that the lectin wheat germ agglutinin induces an activation of p72syk against both auto- and exogenous-substrate-phosphorylation in porcine platelets. The activation of p72syk was abrogated by the coexistence of N-acetyl-D-glucosamine with wheat germ agglutinin. These data suggest that p72syk is a candidate of responsible protein tyrosine kinase for platelet activation and that cell surface glycoprotein is involved in the activation of p72syk in platelets. PMID- 1627136 TI - A putative new juvenile peptide hormone in lepidopteran insects. AB - A growth-blocking peptide (GBP) with repressive activity against juvenile hormone (JH) esterase has been isolated from the last (6th) instar larval plasma of the armyworm Pseudaletia separata (Lepidoptera: Noctuidae) parasitized by the parasitoid wasp Apanteles kariyai (Hymenoptera: Braconidae) (1,2). This study demonstrates that GBP not only exists in the plasma of parasitized last instar larvae, but also in the plasma of unparasitized penultimate (5th) instar larvae, while the plasma of last instar larvae does not contain any detectable amount of GBP. The detection of GBP in unparasitized penultimate instar larvae, before the final larval molt, demonstrates that this factor is naturally occurring in the insect larva before the last larval instar and is seemingly coordinating, along with JH, the regulation of juvenile characteristics. This finding suggests the existence of a new type of juvenile peptide hormone in lepidopteran insects. PMID- 1627135 TI - Inhibition of DNA polymerases by tripeptide derivative protease inhibitors. AB - Benzyloxycarbonyl(Z)-Leu-Leu-Leu-al and dansyl(Dns)-Leu-Leu-Leu-CH2Cl, well known as protease inhibitors, effectively inhibit the activities of DNA polymerases alpha, beta and gamma from rat liver and pol I from Escherichia coli, but the ability of these inhibitors to inhibit terminal deoxynucleotidyl transferase (TdT) is weak. The mode of inhibition by these tripeptide analogues is non competitive with dNTP. The Ki values for Z-Leu-Leu-Leu-al and Dns-Leu-Leu-Leu CH2Cl are 6.25 x 10(-5) M and 6.56 x 10(-5) M, respectively. PMID- 1627137 TI - Competitive protein binding assay for activin A/EDF using follistatin determination of activin levels in human plasma. AB - A sensitive and specific protein binding assay for activin A/EDF (activin) was developed using follistatin as a binding protein and [125I] labelled activin as a tracer. As 50% acetonitrile (CH3CN) separated free and follistatin-bound activin, plasma pretreated with an equal volume of CH3CN was used as the assay sample and B/F separation was also done with 50% CH3CN. The recovery of the assay was 85.0% and its sensitivity was 0.5 ng/ml. Crossreactivity with inhibin A was 1.8%. The mean plasma level of follistatin-free activin in normal subjects was 1.3 +/- 0.7%. (M +/- SD) ng/ml. Plasma free activin levels were generally elevated in patients with chronic renal failure or hematological diseases associated with anemia. PMID- 1627138 TI - Post-translational modifications in the collagen of human osteoporotic femoral head. AB - No detailed biochemical analysis has been made of the possible compositional changes in the collagen relating to the fragility of osteoporotic bone. We report for the first time significant changes in the compositional properties of the collagen. The major differences were observed in the post-translational modifications, namely, in the hydroxylation of lysine residues and the nature of the stabilizing cross-links of the collagen fibre. The increase in hydroxylation was greater in the head region compared to the neck region of the femoral head, whilst the decrease in the intermediate cross-links was greater in the neck region. Clearly, the collagen is altered in osteoporosis and it is important that these changes are recognised in studies of bone metabolism in osteoporosis since they may play a role in the pathogenesis of the disease. PMID- 1627139 TI - Increase in cytoplasmic Ca2+ and stimulation of calcitonin secretion from human medullary thyroid carcinoma cells by the gastrin-releasing peptide. AB - Examination was made of the effects of gastrin-releasing peptide (GRP) on human medullary thyroid carcinoma cells (TT cells). GRP stimulated calcitonin(CT) release in a concentration-dependent manner at 0.1-1000 nmol/l. On adding forskolin along with GRP, CT release was greater than by GRP alone. The stimulatory effect of A23187 was not additive. Intracellular free calcium concentration ([Ca2+]i) was measured for individual TT cells loaded with fura-2. The addition of GRP caused a rapid and transient rise in [Ca2+]i in a concentration-dependent manner followed by a sustained increase in [Ca2+]i. In the medium without Ca2+, this sustained increase did not occur and the concentration of CT release from TT cells by GRP was reduced by approximately a half. GRP would thus appear to be importantly involved in the regulation of thyroid C cell function through modulation of [Ca2+]i. PMID- 1627140 TI - N-and O-acetylation of aromatic and heterocyclic amine carcinogens by human monomorphic and polymorphic acetyltransferases expressed in COS-1 cells. AB - Human monomorphic and polymorphic arylamine acetyltransferases (EC 2.3.1.5) were expressed in monkey kidney COS-1 cells and used to study the N- and O-acetylation of a number of carcinogenic amines and their N-hydroxy metabolites. The monomorphic enzyme N-acetylated the aromatic amines, 2-aminofluorene and 4 aminobiphenyl, and also O-acetylated their N-hydroxy derivatives. None of the food-derived heterocyclic amines (Glu-P-1, PhIP, IQ, MeIQx) were substrates and their N-hydroxy metabolites were poorly O-acetylated by this isozyme. By contrast, the polymorphic acetyltransferase catalyzed the N-acetylation of both aromatic amines, and to a lesser extent, Glu-P-1 and PhIP. However, all six N hydroxy amine substrates were readily O-acetylated to form DNA-bound adducts by the polymorphic isozyme. These data suggest that, for the heterocyclic amine carcinogens, rapid acetylator individuals will be predisposed to their genotoxicity. PMID- 1627141 TI - Molecular cloning of rabbit cytochrome b5 genes: evidence for the occurrence of two separate genes encoding the soluble and microsomal forms. AB - The rabbit genomic segments for the soluble cytochrome b5 (b5) and microsomal b5 were amplified and isolated, respectively, by means of the polymerase chain reaction using primers corresponding to various portions of the open reading frame of microsomal b5 cDNA. The DNA sequence analysis revealed that the soluble b5 gene has an extra 24 nucleotide long insert which encodes a C-terminal amino acid and a termination codon which are specific to the soluble b5. Except for the insert, the sequences of the soluble and microsomal b5 genes are identical with each other from the 5' end to the 3' end of the open reading frame of the microsomal b5 cDNA. Comparison of the genomic sequences with the cDNA sequences suggested that the soluble and microsomal genes are intronless within their open reading frames. These data indicate that rabbit soluble and microsomal b5 mRNAs are encoded by two highly conserved but separate genes. PMID- 1627142 TI - The N-terminal region of HIV-1 integrase is required for integration activity, but not for DNA-binding. AB - HIV-1 integrase binds to both double- and single-stranded DNA with Kd-values of around 20 nM, irrespective of sequence similarities with the termini of the viral LTR. For integration activity, however, the correct LTR sequence of the substrate is required. The putative zinc-binding site present at the N-terminus of the protein is not essential for DNA binding, since deletion mutants of the protein lacking this sequence show similar affinity towards DNA as the wild-type; however, these mutants are not capable of performing the LTR-cleavage and integration reactions. Thus, it appears that the N-terminal part of the integrase is essential for catalytic activity. PMID- 1627143 TI - Ubiquitous nuclear factors bind specifically to a 5'-region conserved in carcinoembryonic antigen-related genes. AB - We recently cloned members of the murine carcinoembryonic antigen (CEA) gene family, some of which are differentially expressed during placental development. By intra- and interspecies sequence comparisons, we identified an element in the putative promoter and/or 5'-nontranslated region which is conserved within all human and rodent CEA-related genes analyzed so far. Using gel retardation analysis and DNaseI hypersensitive site mapping, we now show that ubiquitously expressed nuclear factors specifically bind to the conserved region derived from the mouse gene Cea-2 in vitro and probably also in vivo. Another DNaseI hypersensitive site lies within or close to a simple sequence motif [(GGA)n] located in the first intron of Cea-2. Such sequences have been reported to play a role in the regulation of certain genes. Therefore, this analysis has identified putative regulatory regions for Cea-2 and possibly CEA-related genes in general. PMID- 1627144 TI - Growth inhibition of N1E-115 mouse neuroblastoma cells by c-myc or N-myc antisense oligodeoxynucleotides causes limited differentiation but is not coupled to neurite formation. AB - Antisense oligodeoxynucleotides were found to be stable in the culture medium containing fetal calf serum (heat-inactivated 30 minutes at 65 degrees C) and in cells. Antisense oligomer treatment causes cessation of mitoses, but does not lead to morphological differentiation. Under antisense conditions, we have observed an increase in the amount of two neurospecific protein, namely peripherin and gamma-enolase. Comparison of the results obtained with chemical inducers and antisense oligodeoxynucleotides allows us to postulate three phases in N1E-115 differentiation: the first correspond to the arrest of mitosis, the second to the expression of a limited neuronal program, and the third to the morphological and electrophysiological differentiation. PMID- 1627145 TI - Nonoxidative ethanol metabolism: expression of fatty acid ethyl ester synthase III in cultured neural cells. AB - Alcohol metabolism in the human brain has been characterized as essentially nonoxidative in nature, with the esterification of ethanol with fatty acids via fatty acid ethyl ester synthase. This pathway of ethanol metabolism is related to end organ damage in the brain but the neural cell type expressing FAEES has not been identified. In this study human and rodent neuroblastoma and glioma cell lines are assayed for fatty acid ethyl ester synthase activity. Cells with neuronal properties demonstrated higher activity than glioma cell lines. We confirmed the presence of the mRNA for one type of synthase, fatty acid ethyl ester synthase-III in three neuronal cell lines--N1E115 cells, PC12 cells, and SK N-MC cells. These results support the hypothesis that FAEES activity is expressed chiefly in cells with neuronal properties and suggest that non-oxidative ethanol metabolism is potentially related to the toxic effect of ethanol on the human brain. PMID- 1627147 TI - Synthesis and structure-activity relationships of elafin, an elastase-specific inhibitor. AB - Elafin, an elastase-specific inhibitor isolated from human skin, and its related peptides were synthesized by the solution procedure, and their inhibitory activities were measured against various enzymes. During the oxidative folding reactions of the reduced peptides, the ratio of the active product to the inactive product was varied by changing the concentration of guanidine HCl and the amount of redox reagents. The disulfide structures of fully active synthetic elafin and the inactive product were determined by amino acid analysis, gas-phase sequencing and mass spectrometry of their proteolytic fragments. The relationship between structure and inhibitory activities and/or the folding reaction was examined and the amino terminal part of the elafin molecule was found to have a great influence on the folding reactions, but not on the inhibitory activities. PMID- 1627146 TI - Estrogen receptor-induced bending of the Xenopus vitellogenin A2 gene hormone response element. AB - DNA bending is increasingly proposed as an essential step for the establishment of the multiprotein complexes required for transcription initiation. Polyamines and metallic cations, known to promote DNA-bending, enhance the binding of purified estrogen receptor (ER) to the estrogen response element (ERE) of the Xenopus vitellogenin A2 gene. Using both circular permutation electrophoretic mobility and cyclization assays, we provide evidence that ER bends the DNA at the estrogen response element. The same bending occurs as a result of estrogen receptor protein binding independently of its conformational changes induced by hormone or anti-hormone. We suggest a role of the observed DNA bending in estrogen-regulated transcription. PMID- 1627148 TI - Activin A increases cytosolic free calcium concentration in rat pituitary somatotropes. AB - The effect of activin A on the cytosolic free calcium concentration ([Ca2+]i) in normal rat pituitary cells was examined using a calcium sensitive fluorescent dye, indo 1 AM, and a digital imaging fluorescent microscope system. The cells showing an increase in [Ca2+]i in response to activin A were then characterized by comparison with cells responding to growth hormone releasing hormone (GRH), thyrotropin releasing hormone (TRH), corticotropin releasing hormone (CRH), and gonadotropin releasing hormone (GnRH) in monolayer cultures of normal rat pituitary cells. Activin A increased [Ca2+]i in some cells in a mixed population of normal rat pituitary cells. The cells that responded to activin A also responded to GRH. Most of these cells were not affected by other tropic hormones (CRH, TRH, and GnRH), but a few cells responded to both GRH and TRH. None of the activin A-responding cells responded to CRH or GnRH, and none of the CRH- or GnRH responding cells responded to activin A. In a preparation of somatotropes purified 80-90% by fluorescence-activated cell sorting, activin A increased [Ca2+]i in 30% of the cells that shows a [Ca2+]i-response to GRH. These findings suggest direct involvement of somatotropes in activin A-induced biological events in the rat pituitary gland. PMID- 1627149 TI - Prostacyclin administration suppresses the increase in hepatic levels of COL1A(I) and glyceraldehyde-3-phosphate dehydrogenase mRNAs in the rat treated with carbon tetrachloride. AB - Northern analysis using total RNAs from the component cells of normal rat liver indicated that COL1A(I) mRNA is present in fat-storing cells (Ito cells) and sinusoidal endothelial cells. A fraction for Kupffer cells also contained this mRNA. When CCl4 was given, COL1A(I) mRNA was increased in a factor of 1.5 in the fractions of these component cells. After 48 h of the drug administration, hepatocytes appeared to possess over 60% of liver COL1A(I) mRNA, although in normal hepatocytes its level was below the range detectable by our procedures. Under this injured condition of liver, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA level was elevated, while activity of this enzyme was lowered by 50% of the control value. All the changes were obviously suppressed by the simultaneous administration of prostacyclin. PMID- 1627150 TI - Identification of two types of homologous DNA pairing activity in mouse cells. AB - We have identified two types of homologous DNA pairing activity in mouse cell extracts by a strand-transfer assay. Both activities are separated from each other by anion-exchange chromatography; neither of them needs ATP. One requires magnesium ion and is stimulated by Escherichia coli single-stranded DNA binding protein, whereas the other does not require the ion and shows a higher affinity for a left-handed Z-DNA. PMID- 1627151 TI - Identification of a gene encoding for the human formyl peptide receptor. AB - The neutrophil FMLP receptor is involved in activation and subsequent response to certain chemotactic stimuli. The normal receptor has been reported to consist of several components, ranging in size from 43-94 kDa, and to contain both high and low affinity states. However, limited information is available on the gene/s which encode for the receptor. In this study, we have generated oligonucleotide probes derived from a published cDNA sequence encoding for one of the components of the FMLP receptor, and used these probes to amplify genomic DNA from HL-60 cells as well as normal human neutrophils, using the polymerase chain reaction. Such procedure resulted in the amplification of a single, approximately 1 kb fragment of genomic DNA identical in sequence to the cDNA described in the literature for one of the isoforms of the receptor. This finding supports the notion that the human FMLP receptor is encoded by at least one, intronless gene. PMID- 1627152 TI - Importance of iron in lipid peroxidation in the tyrosinase/4-hydroxyanisole system: possible mechanism of killing of malignant melanoma cells by 4 hydroxyanisole. AB - Phospholipid peroxidation of unsaturated phospholipid liposomes in the tyrosinase(mushroom)-4-hydroxyanisole system was studied in both the presence and absence of Fe3+, as a model of melanocyte damage by this agent. Ferric ion is required for the lipid peroxidation, and maximal lipid peroxidation was achieved with a molar ratio of [Fe3+]/[4-hydroxyanisole] of about 1. The lipid peroxidation was significantly inhibited by ceruloplasmin (a ferroxidase), indicating that Fe3+, which would be coordinated with metabolites, catechols, should be reduced to express its oxidant property. Judging from the results obtained with inhibitors or scavengers of active oxygen species, O2-, H2O2, and .OH would not mainly involve in the lipid peroxidation. PMID- 1627153 TI - Characterization of a trypsin inhibitor from equine urine. AB - A trypsin inhibitor was isolated from pregnant mares' urine by adsorption on bentonite and elution with aqueous pyridine followed by batch DEAE-cellulose treatment and column chromatography. Final purification to an electrophoretically homogenous glycoprotein was achieved by gel permeation chromatography. This equine urinary trypsin inhibitor (E-UTI) is acid- and heat-stable, has a molecular weight of 22 to 23 kDa, an isoelectric point of 4.55, forms a 1:1 molar complex with trypsin and has serine as its N-terminal amino acid. The N-terminal amino acid sequence of this protein is almost identical with that of EI-14, the inhibitor obtained from horse serum by tryptic treatment, except for two extra amino acid residues, Ser-Lys- on the N-terminal end of E-UTI. In its isoelectric point E-UTI differs from EI-14 and the inhibitor from human urine. PMID- 1627155 TI - Morphological differences in crystals of multiple forms of yeast transketolase. AB - Monocrystals of three individual multiple forms of yeast transketolase (A, B and C) differing in their thermostability have been obtained. Ammonium sulfate was used as a precipitating agent. Crystals of the mentioned forms were found to possess different morphology and stability during storage. Single crystals growing from the enzyme form C within 4-7 days were subsequently destroyed. Simultaneously, in the preparation, microcrystals started to grow in a great number. They were found to correspond morphologically to crystals obtained from transketolase A. A possibility of interconversions of the enzyme forms in sequence C----A----B is discussed. PMID- 1627154 TI - Trypsin inhibitors of buffalo seminal plasma. AB - Two trypsin inhibitors from acid-treated buffalo seminal plasma were purified by gel filtration and affinity chromatography. These acid-stable trypsin inhibitors having charge heterogeneity were homogeneous with respect to size as revealed by gel filtration and SDS-PAGE. Gel filtration data suggest molecular weight value of 9,900 Da for inhibitor I and 10,900 Da for inhibitor II. Molecular weight estimated by SDS-PAGE was found to be 10,600 Da and 11,200 Da for inhibitors I and II, respectively. The hydrodynamic properties such as Stokes radii (1.58 nm and 1.62 nm); intrinsic viscosity (2.5725 ml/g and 2.5025 ml/g) and diffusion coefficient (13.499 x 10(-11) m2/sec. and 13.166X10(-11) m2/sec) respectively for inhibitor I and II were determined by analytical gel filtration. These inhibitors were fairly thermostable and could not be stained by PAS reagent. Both the inhibitors were found to inhibit buffalo acrosin but not bovine chymotrypsin. PMID- 1627156 TI - Age-dependent 6kb deletion in human liver mitochondrial DNA. AB - Using PCR technique, restriction mapping and DNA sequencing, we analyzed liver mitochondrial DNA (mtDNA) of 2 stillborn babies and 62 Chinese subjects with non liver disease from 27 to 86 years old. The results showed an age-dependent 6,063 bp deletion in the liver mtDNA of older subjects. We found a TAACAGAC sequence flanking the 5'-end breakpoint at 7,842 nucleotide position and an imperfect repeat sequence CAACATAC flanking the 3'-end breakpoint at 13,905 nucleotide position. The incidence of the deleted mtDNA was found to increase with age. The deleted mtDNA was not detected in the liver of the stillbirth or blood cells of all the subjects. This is the first account that an age-related 6,063 bp deletion occurs in the liver mtDNA of old humans. The occurrence of this and previously reported 4,977 bp deletions is consistent with our recent finding that liver mitochondrial respiratory functions decline with age and support the hypothesis that continuous accumulation of mtDNA mutations is an important contributor to ageing process in the human. PMID- 1627157 TI - Reduction of immunoreactivity of bovine serum albumin conjugated with polyethylene glycol(PEG) in relation to its esterase activity. AB - Bovine serum albumin was modified with activated PEG2, 2,4-bis[O methoxypoly(ethylene glycol)]-6-chloro-s-triazine. The PEG-modified albumin, in which 15 out of the total 60 amino groups in the albumin molecule were coupled with activated PEG2, lost immunoreactivity towards anti-albumin serum and retained 63% of the esterase activity of native albumin. PMID- 1627158 TI - Phosphatidic acid with medium-length fatty acyl chains synergistically stimulates phospholipase C with Ca2+ in rabbit platelets. AB - The mode of phospholipase C activation in platelet cells induced by didecanoyl (C10)-phosphatidic acid (PA) was investigated with washed rabbit platelets. The C10-PA dose-dependently induced aggregation and serotonin secretion, as well as increases in cytoplasmic free Ca2+ concentration and 1,2-diacylglycerol formation. None of these responses was evoked unless Ca2+ had been added to the platelet suspension. Furthermore, under the conditions of various intracellular Ca2+ concentrations which were set by treatment of the cells with ionomycin and Ca2+, C10-PA promoted 1,2-diacylglycerol formation only at the Ca2+ concentration of 300 nM or higher, whereas thrombin induced the formation even at 100 nM Ca2+. These results suggest that PA activates platelet phospholipase C in cooperation with Ca2+ and contributes to platelet activation through such an effect. PMID- 1627159 TI - Interaction of membrane phospholipids with some DNA substructures studied by means of differential scanning calorimetry. AB - The interaction of dipalmitoylphosphatidylcholine, dipalmitoylphosphatidic acid and dipalmitoylphosphatidylethanolamine with some DNA substructures such as cytidine, uridine, adenosine 5'di- and triphosphate, guanosine 5'mono- and diphosphate, cytidine 5'mono- and triphosphate, uridine 5'mono- and triphosphate and inosine 5'monophosphate was studied with differential scanning calorimetry. The dependence of pretransition and main transition temperatures and the enthalpy of main transition on the molecular characteristics of the interacting molecular species was calculated by stepwise regression analysis. Nucleosides and nucleotides increased the main transition temperature and peak half width of phospholipids and they decreased the enthalpy of main transition proving the existence of interaction between phospholipids and DNA substructures. Calculation proved that the interaction is mainly of hydrophilic character but the involvement of hydrophobic forces or steric conditions cannot be ruled out. PMID- 1627160 TI - Structure of a Micrococcus lysodeikticus cell wall fragment containing phosphorylated sugars. AB - A polysaccharide-peptidoglycan complex containing different phosphorylated sugars from Micrococcus lysodeikticus cell wall has been isolated and purified. The peptidoglycan contained muramic acid 6-phosphate and N-acetylglucosamine 6 phosphate as phosphorylated sugars in addition to other sugar residues. Mild acid hydrolysis of the peptidoglycan and subsequent reduction of the released polysaccharide showed therein the presence of glucose and N-acetyl-glucosamine in the linkage of the external polysaccharide residues to the peptidoglycan through phosphodiester linkage. These data suggest the presence of polysaccharide chains linked to a peptidoglycan core through two phosphorylated sugars via two different terminal carbohydrate residues of the external polysaccharide chains in a same polymer. PMID- 1627161 TI - Trehalase activity and its regulation during growth of Saccharomyces cerevisiae. AB - Trehalase activity decreased in 95% at the onset of the transition phase of growth of S. cerevisiae. The question which we raised was whether this phenomenon was due to proteolysis or to conversion of the enzyme to a less active form (dephosphorylation). Immunological methods allowed to identify the presence of the trehalase protein during cell growth. At the same stage of growth, an increase in the non-phosphorylated enzyme was detected "in vitro". Results utilizing mutant strains also indicated that regulation occurred by interconversion of forms. The same mechanism also seems to control trehalase activity in non proliferating conditions. PMID- 1627162 TI - Nuclear S1 proteins from the starfish Asterina pectinifera. AB - Nuclear S1 proteins are a group of proteins apparently ubiquitous in vertebrate cell nuclei. They were originally isolated at pH 4.9 from the supernatant of rat liver nuclei mildly digested with DNase I. In the present study, under the conditions identical to those employed for vertebrate cells, we identified two S1 proteins in the starfish Asterina Pectinifera. Their molecular weights are 47,200 and 39,000. This finding suggests widespread occurrence of S1 proteins in eukaryotes and their basic function in the cell nucleus. PMID- 1627163 TI - E. coli gpt gene expression effects on K562 human leukemia cell proliferation and erythroid differentiation altered by mycophenolic acid. AB - Inosine monophosphate dehydrogenase (IMPDH, EC 1.1.1.205) inhibitors including mycophenolic acid (MPA) were reported to induce K562 human leukemia cells to differentiate into erythroid cells. A shuttle vector plasmid pMSG containing E. coli xanthine-guanine phosphoribosyl transferase (Eco gpt) gene was transfected into K562 cells (K562-pMSG cells) to investigate the role of IMPDH in both K562 cell proliferation and erythroid differentiation. Eco gpt provides K562 cells with an additional salvage pathway for GMP production from xanthine. In the presence of xanthine, K562-pMSG cells continued to proliferate and did not differentiate to erythroid cells regardless of the presence of MPA, but they discontinued proliferating and differentiated into the erythroid lineage in the absence of xanthine. Proliferation and differentiation of control K562 cells into erythroid cells were suppressed by MPA regardless of the presence or absence of xanthine. Addition of guanosine maintained the proliferation and blocked the erythroid differentiation of K562 and K562-pMSG cells induced by MPA even in the absence of xanthine. These data indicate that a decrease in the activity of IMPDH and a subsequent decline in the concentration of guanine nucleotides caused by MPA resulted in the induction of the erythroid differentiation and discontinuation of the proliferation of K562 cells. PMID- 1627164 TI - A method for determination of transketolase activity based on the use of a pH indicator. AB - A new method for assaying transketolase activity is proposed. The method consists in recording the pH changes in the course of the enzymatic reaction and is based on the use of the pH-indicator p-nitrophenol. When p-nitrophenol is added to a reaction mixture containing hydroxypyruvate and glycolaldehyde as substrates the absorbance increases. The rate of the change of absorbance is proportional to the enzyme concentration. PMID- 1627165 TI - Effect of chronic insecticide, phosalone, toxicity on haem synthesis and blood gas composition in the rat. AB - The influence of multiple sublethal concentrations of phosalone on whole animal and kidney oxygen consumption, haem synthesis and blood gases of rat, were carried out over a 90 day dosed period. The results indicate the existence of hypoventilation and a hypoxic condition in the animals which lead to the disruption of neuromuscular transmission in respiratory muscles and increase of erythropoiesis and haemoglobin synthesis. The changes were most pronounced when animals were exposed for the 90 day dosed period. PMID- 1627166 TI - Binding of anti-human-interleukin-6 monoclonal antibodies to synthetic peptides of human interleukin-6 studied using surface plasmon resonance. AB - Biosensor technology employing surface plasmon resonance (SPR) detection provides a highly-sensitive (sub ng), non-extrinsic labelling approach for monitoring protein interactions in real-time. We have used this approach to map the binding sites on human interleukin-6 (hIL-6) for a series of anti-hIL-6 monoclonal antibodies (mAbs). Epitopes were localised by monitoring the ability of ten synthetic peptides, spanning the sequence of hIL-6, to inhibit the binding of anti-hIL-6 mAbs to immobilised hIL-6. Peptide P8 (Pro139-Gln153) inhibited binding of anti-IL-6-mAbs 1, 2 and 7. To increase the sensitivity of detection of antibody-synthetic peptide interactions, a procedure was developed for immobilising the synthetic peptides directly to the sensor surface of the SPR instrument. From this study, association equilibrium constants of 2.1 x 10(6)M-1 and 3.6 x 10(4)M-1 were calculated for the mAb7-immobilised P8 and mAb7-free P8 interactions, respectively. PMID- 1627167 TI - The generation of big-endothelin (1-22) (endothelin-valine) from big-endothelin in the soluble fraction of porcine lung. AB - The degradation of big-endothelin (big-ET) in the soluble fraction of porcine lung was investigated. The degradation in the presence of p-chloromercuribenzoate (PCMB), pepstatin A, and EDTA resulted in the accumulation of two newly-formed fragments, big-ET (23-39) and big-ET (1-22), the latter called endothelin-valine (ET-Val). The generation of the two fragments was inhibited by diisopropylfluorophosphate (DFP). The enzyme responsible, called ET-Val generating endopeptidase, was isolated from porcine lung by a procedure including chromatographies on columns of DEAE-cellulose, hydroxylapatite, Mono Q, p mercuribenzoate-Sepharose, and Superose 6. The molecular weight of the enzyme was 140,000 and the pH optimum of the activity was 7.0. The activity was strongly inhibited by DFP, but scarcely inhibited by PCMB, EDTA, and pepstatin A. Thus, the isolated enzyme was classified as a serine protease cleaving big-ET at the Val22-Asn23 bond. PMID- 1627168 TI - Sensitivity in vitro of mature and immature mouse thymocytes to dexamethasone cytotoxicity and its correlation to poly ADP-ribosylation. AB - Mouse thymocytes were fractionated into heavy (subtype I, 79% of total cell number), medium (subtype II, 18%) and light (subtype III, 3%) ones by Percoll density centrifugation and they were identified as immature (subtype I and II) and mature (subtype III) thymocytes based on their proliferative response to mitogens. Whereas the nuclear activity of poly (ADP-ribose) polymerase (EC 2.4.2.30) in the subtype III was only one half that of denser subtypes, it increased two-fold upon mitogen stimulation. The sensitivity of three thymocyte subtypes to the dexamethasone cytotoxicity, as judged by the extent of the DNA cleavage, depletion of NAD and cell viability, was highest in the subtype I and lowest in the subtype III. The possible involvement of poly ADP-ribosylation in the apoptotic (programmed) cell death during intrathymic development of immature to mature thymocytes is discussed. PMID- 1627169 TI - mRNA containing an extended Shine-Dalgarno sequence is translated independently of ribosomal protein S1. AB - The role of ribosomal protein S1 in the translation of mRNA containing an extended Shine-Dalgarno sequence was investigated. Using the toeprinting technique, formation of the ternary initiation complex between 30S subunits, both S1-depleted or treated with anti-S1 antibodies, and mini-mRNA containing the 9 nucleotide-long Shine-Dalgarno sequence was studied. It was concluded that the initiation of translation on mRNA with an extended Shine-Dalgarno sequence is S1 independent. It was demonstrated that S1-depleted ribosomes effectively translate the cro-mini-mRNA in a cell-free system. In contrast to cro-mini-mRNA, 30S subunits without protein S1 are inactive in ternary initiation complex formation with, and cell-free translation of, MS2 or fr phage RNAs and RNA protein III of phage fd. PMID- 1627170 TI - Lectin extracts of champedak seeds demonstrate selective stimulation of T lymphocyte proliferation. AB - The effect of extracts of champedak (Artocarpus integer) seed lectin on the proliferation of normal human lymphocyte was investigated. The IgA1 binding lectin was demonstrated to stimulate the proliferation of human peripheral blood mononuclear cells. Action of the lectin on enriched T and B cell populations demonstrated T lymphocyte specificity. The lectin was not mitogenic to B lymphocytes. Optimal stimulation of proliferative response was achieved when cells were subjected to 5 days exposure to the crude lectin at 20 micrograms/ml. PMID- 1627171 TI - Analysis of Vipera russelli venom using polyclonal antibodies prepared against its purified toxic phospholipase A2 VRV PL-V. AB - Vipera russelli venom induces predominantly neurotoxic, myotoxic necrotic and hemorrhagic symptoms in experimental animals and has several hydrolytic enzyme activities. In this study, V. russelli venom is characterized both as a PLA2 and as a toxin. Anti PL-V Ig (antibodies to a toxic phospholipase A2 VRV PL-V of V. russelli venom) nullifies the toxicity of whole V. russelli venom to a great extent. The neurotoxic symptoms vanish completely in the presence of anti PL-V Ig. The cross reacting components of whole V. russelli venom were removed by precipitating them from whole venom by the addition of anti PL-V Ig. The non cross reacting components present in the supernatant were checked for toxicity. There was a significant reduction in toxicity. The LD50 value of the supernatant had increased from 4.1 mg/kg body weight to 11.7 mg/kg body weight and it showed about 34% of the total venom phospholipase A2 activity. It had edema forming, hemorrhagic and hemolytic activity but failed to induce neurotoxic, anticoagulant and myotoxic effects. PMID- 1627172 TI - A small proteoglycan isolated from human cartilage containing a nonfunctional hyaluronic acid binding region. AB - A low buoyant density fraction (A4) was isolated from human cartilage by CsCl density gradient ultracentrifugation. This fraction contained a hydrodynamically small proteoglycan (Kav, 0.74 on Sepharose CL-2B) that reacted with monoclonal antibody 12/20/1C6 specific for the hyaluronic acid binding region (G1 globe) of the large aggregating high-density proteoglycan isolated from many animal cartilages. Despite the presence of the hyaluronic acid binding region, this small proteoglycan did not form proteoglycan aggregates with hyaluronan, not even in the presence of link protein. PMID- 1627173 TI - RNA unwinding by eukaryotic initiation factor 4A and nucleotide modification. AB - Unwinding of double-stranded RNA by nuclear helicases can lead to modification of adenosine-residues, resulting in inosine. During initiation of protein synthesis the 5' untranslated region of an mRNA is unwound by eukaryotic initiation factors (eIF) -4A and -4B. In this work we investigated the possible nucleotide modification after unwinding by eIF-4A and eIF-4B of in vitro synthesized, labeled RNA. The products of unwinding were analyzed by gel-electrophoresis and, after nuclease digestion, by thin layer chromatography of the mononucleotides. Crude protein fractions unwound the duplex RNA and converted part of the AMP residues into IMP-residues. However, unwinding by purified factors was not linked to this conversion, the deamination of AMP residues. Concluding, unwinding of RNA during initiation of protein synthesis does not lead to conversion of adenosine into inosine. PMID- 1627174 TI - Facile cloning and sequencing of S-crystallin genes from octopus lenses based on polymerase chain reaction. AB - S-crystallin is a major lens protein present in the octopus and squid of Cephalopods. To facilitate the cloning of the protein, cDNA was constructed from the poly(A)+RNA of octopus lenses, and amplification by polymerase chain reaction (PCR) was carried out with two primers designed according to the 5'- and 3' coding regions of S-crystallin gene. Sequencing two of 15 positive clones obtained shows 37-44% similarity in nucleotide and 23-30% similarity in amino acid sequences as compared with mammalian glutathione S-transferases (GST), revealing that S-crystallins exist as a multigene family and probably derived from GST by gene duplication and subsequent mutational base replacements. PMID- 1627175 TI - Enzymatic reduction of shogaol: a novel biotransformation pathway for the alpha,beta-unsaturated ketone system. AB - A novel reductive metabolism of 1-(4-hydroxy-3-methoxyphenyl)-deca-4-ene-3-one (shogaol), a pungent principle of ginger, was investigated in rat liver in vitro. Ethyl acetate-extractable metabolites of shogaol formed by incubation of this alpha,beta-unsaturated ketone with rat liver cytosolic fraction fortified with NADPH or NADPH-generating system were isolated, and two major metabolites were identified as 1-(4-hydroxy-3-methoxyphenyl)-decan-3-one (paradol) and 1-(4 hydroxy-3-methoxy)-decan-3-ol (reduced paradol). 1-(4-hydroxy-3-methoxyphenyl) deca-1-ene-3-one (dehydroparadol), a non-pungent analog of shogaol, formed the same metabolites as did shogaol under similar incubation conditions. Paradol appears to be an intermediate in the reductive metabolism of the alpha,beta unsaturated ketone moiety of shogaol to the corresponding saturated alcohol. PMID- 1627176 TI - Preparation of monoclonal antibodies against a poly(U), poly(C) specific ribonuclease prepared from the insect Ceratitis capitata. AB - A poly(U), poly(C) specific RNase of apparent MW 34 kDa has recently been purified from 6 day old larvae of the insect Ceratitis capitata. Two monoclonal antibodies were obtained by immunizing mice with this protein. Immunoblot analysis of the RNase revealed that both antibodies recognize the 34 kDa protein. Furthermore, immunoprecipitation experiments show that both antibodies were capable of precipitating the ribonuclease without affecting its catalytic activity. PMID- 1627177 TI - Serine base-exchange in rat liver microsomes: effect of phospholipids. AB - We enriched liver microsomes in lipid classes and molecular species disrupting membranes with octyl glucoside and reassembling them by detergent removal. Phosphatidylethanolamine incorporated into membranes better than phosphatidylserine or phosphatidylcholine. In addition, the degree of incorporation depended on the unsaturation of fatty acyl-chains. The enrichment of the membranes with phosphatidylserine or phosphatidylcholine inhibited serine base-exchange, whereas the addition of phosphatidylethanolamine usually stimulated it. The effect of exogenous lipids also depended on molecular species; egg yolk phosphatidylcholine and dipalmitoyl phosphatidylcholine inhibited base exchange whereas the effect of palmitoyl-oleoyl phosphatidylcholine depended on the incorporated amount. The degree of unsaturation also modulated the effect of phosphatidylethanolamine. PMID- 1627178 TI - Simplified construction and characterization of yeast artificial chromosome libraries. AB - Three yeast artificial chromosome (YAC) libraries were constructed using two human cell lines and the pYAC-RC vector. The main differences from the previously described methods were: i) genomic DNA was digested in low melting point (LMP) agarose blocks with the rare cutting enzyme ClaI; ii) DNA was ligated in melted LMP agarose after agarase treatment; iii) spheroplast regeneration plating was done in calcium alginate thin layer. In addition, a panel of PCR primers was used to identify quickly the presence in the libraries of repetitive and single copy human DNA sequences. PMID- 1627179 TI - Plasmodium falciparum synthesizes O-glycosylated glycoproteins containing O linked N-acetylglucosamine. AB - Asexual blood forms of the human malaria parasite, Plasmodium falciparum, synthesize a major glycosylated 195 kDa protein that has been considered for the development of a vaccine. beta-Elimination-borohydride reduction of the 195 kDa glycoprotein and its 16 kDa processed product after metabolic labeling of their carbohydrates, showed the presence of derived, labeled glucosaminitol and alanine. This suggests that the 195 and 16 kDa glycoproteins contain distinct O glycosyl linkages and that N-acetylglucosamine and serine residues are involved in the attachment of carbohydrate moieties to the protein core. Endo-O-glycanase treatment of total glycoproteins shows that O-glycosidycally-linked sugars represent a major carbohydrate moiety in P. falciparum glycoproteins. PMID- 1627180 TI - ATP synthesis in plasma membrane enriched particles by the action of insulin and related growth factors. AB - Early biosynthesis of short-life ATP was observed in plasma membranes of target cells stimulated by insulin or other polypeptide growth factors in the presence of all components of aerobic phosphorylation and cytochrome c. The effect is always mediated by the binding of insulin or growth factors to specific receptors. Erythrocyte plasma membranes are a convenient model to study the phenomenon. Insulin-stimulated synthesis of the plasma membrane "signal" ATP in an amount of 1-10 nM is potentized by ionophores carbonyl cyanide p trifluorometoxyphenylhydrazone and monensin and inhibited by amiloride and ouabain. It is supposed that the plasma membrane "signal" ATP readily generated in response to a growth or mitogenic factor is an "amplifier" or "coupling agent" in the transduction of a signal to growth, proliferation, and mitogenesis. Biosynthesis of the plasma membrane "signal" ATP seems to be associated with partial reversion of Na+, K+ -ATPase with the participation of the plasma membrane redox chain as a proton generator. PMID- 1627182 TI - Sertaconazole (FI-7045). A new antifungal agent. PMID- 1627181 TI - Metabolic and functional changes in macrophages of rats fed polyunsaturated or saturated fatty acid rich-diets during ageing. AB - Previous reports from our laboratory showed that rats fed a polyunsaturated fatty acid-rich diet (UC), during an acute intervals, present important changes in macrophage metabolism and function, while a saturated fatty acid diet (SC) did not induce significant changes (10). In this study, two important questions were addressed: 1. the persistence of the changes induced by the UC and 2. the effect of a SC offered during ageing. The maximal activities of hexokinase, glucose-6 phosphate dehydrogenase, glutaminase, citrate synthase and glutathione peroxidase and the total content of lipid peroxides were measured in resident and inflammatory macrophages of rats fed control chow (CC), UC or SC during 14 months. Intraperitoneal cell migration by thioglycollate injection and the phagocytosis capacity were also evaluated. The results indicate that: 1) the changes caused by UC are exacerbated during ageing, and 2) the SC, given during a prolonged period of time, also caused important alterations of macrophage metabolism and function. PMID- 1627183 TI - Sertaconazole (FI-7045). A new antifungal agent. Introduction. PMID- 1627184 TI - Synthesis and antimycotic activity of (benzo[b]thienyl)methyl ethers of 1-(2,4 dichlorophenyl)-2-(1H-imidazol-1-yl)-ethanol and of (Z)-1-(2,4-dichlorophenyl)-2 (1H-imidazol-1-yl)ethanone oxime. AB - A new series of (benzo[b]thienyl)methyl ethers of 1-(2,4-dichlorophenyl)-2-(1H imidazol-1-yl)ethanol and of (Z)-1-(2,4-dichlorophenyl)-2-(1H-imidazol-1 yl)ethanone oxime were synthesis and tested for antifungal activity. Series design, synthesis, preliminary antimycotic data and structure-activity relationships are reported. 7-Chloro-3-[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1- yl)ethoxymethyl]benzo[b] (8i, Sertaconazole, FI-7045, CAS 99592-32-2) and its nitrate were selected for further research. PMID- 1627185 TI - Physico-chemical properties, analytical determinations and stability of sertaconazole nitrate. AB - Sertaconazole nitrate, the nitrate salt of 7-chloro-3-[1-(2,4-dichlorophenyl)-2 (1H-imidazol-1-yl)ethoxy-methyl] benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2), is a new azole antifungal, which has proved to have a wide spectrum and high activity. This paper describes its physico-chemical properties, structural identification including polymorphism, detection of impurities, determination of related compounds, separation, quantification and purity assays using high-performance liquid chromatography (HPLC) and quantitative assays specially elemental and functional analysis. Stability of sertaconazole nitrate in solid form under accelerated (light, humidity and temperature) and real time conditions and in suspension form at different pH values (acid and basic) was also studied. The results show that sertaconazole nitrate is extremely stable under all the conditions tested, both in solid and in suspension form. Sertaconazole nitrate in solid form packaged in tight sealed amber glass bottles was stable for over 5 years under normal storage conditions. PMID- 1627186 TI - In vitro activity of sertaconazole. AB - The activity of 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl) ethoxy methyl]benzo[b]thiophene (sertaconazole, FI 7045, CAS 99592-32-2), a new topical antifungal, was studied in vitro against several infecting organisms. The results obtained show that sertaconazole is a broad-spectrum antifungal against yeasts (C. albicans, C. tropicalis, C. pseudotropicalis, C. krusei, Trichosporon and Cryptococcus), dermatophytes (Microsporum, Trichophyton and Epidermophyton), opportunistic filamentous fungi (Aspergillus) and Gram-positive bacteria. The MIC (minimum inhibitory concentration) values for the fungistatic activity were between 0.35 and 5.04 micrograms/ml for yeasts and between 0.24 and 2 micrograms/ml for dermatophytes; even partial activities (IC25) against these organisms were obtained at concentrations 10 times lower than those mentioned. At concentrations superior to MIC (MFC between 0.5 and 16 micrograms/ml), sertaconazole exhibited fungicidal activity. PMID- 1627187 TI - In vitro antifungal activity of sertaconazole. AB - The antifungal activity of 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H- imidazol-1 yl)ethoxy-methyl]benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2) versus miconazole has been studied in vitro against yeast-like fungi, dermatophytes and other filamentous fungi. Candida albicans was very sensitive to sertaconazole both in serotype A and serotype B strains (MIC = 0.21 micrograms/ml). Sensitivity of Candida non albicans species (MIC = 0.17 microgram/ml), Torulopsis (MIC = 0.09 microgram/ml) and Trichosporon (MIC = 0.09 microgram/ml) was also remarkable. For dermatophytes, partial inhibitions were observed at concentrations of 0.04 and 0.09 microgram/ml, the 50% inhibition ranging between 0.36 and 12.56 micrograms/ml for most strains. Filamentous opportunistic fungi were less sensitive to azoles, although sertaconazole MICs were lower than those of miconazole. Sertaconazole also proved to possess a remarkable fungicidal activity on all strains of Candida albicans under study. PMID- 1627188 TI - In vitro comparative study of the fungistatic and fungicidal activity of sertaconazole and other antifungals against Candida albicans. AB - The fungistatic and fungicidal activity of 7-chloro-3-[1-(2, 4-dichlorophenyl)-2 (1H-imidazol-1-yl)ethoxy-methyl]benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2) against Candida albicans was determined and compared with that obtained for other antifungals. The fungistatic activity of sertaconazole, evaluated through the MIC obtained in Sabouraud and YNB media, gave results comparable to those obtained with miconazole and clotrimazole, and superior to those presented by bifonazole and ketoconazole. The fungicidal activity, evaluated by means of the 90% reduction in viable cells, took place at a concentration of 8 micrograms/ml for sertaconazole and at higher concentrations for the other drugs studied. PMID- 1627189 TI - In vivo activity of sertaconazole in experimental dermatophytosis in guinea pigs. AB - The comparative curative effect of 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H- imidazol-1-yl)ethoxy-methyl]benzo [b]thiophene (sertaconazole, FI-7045, CAS 99592 32-2) (SZ) and miconazole (MZ) 2% creams in a model of dermatomycosis caused by Trichophyton mentagrophytes in guinea pigs was studied. Two treatments of different duration (12 and 3 days) were applied, and their efficacy versus infected and untreated animals (control group) was evaluated according to clinical parameters (degree of alopecia and lesion) and microbiological healing (recovery of T. mentagrophytes from hair pulled from the infected site). The therapeutic effect resulting from the application of the creams for 12 days was excellent and similar for both test creams; however, the application of SZ cream for 3 days had greater therapeutic effect than MZ cream according to the improvement of clinical symptoms and microbiological healing. PMID- 1627190 TI - Inhibition of ergosterol synthesis by sertaconazole in Candida albicans. AB - 7-Chloro-3-[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl) ethoxy-methyl] benzo [b] thiophene (sertaconazole, FI-7045, CAS 99592-32-2), a new topical antifungal agent, has shown activity against a broad range of clinically relevant yeasts and fungi. In the present study, the molecular basis of the pharmacological action of sertaconazole was examined by investigating the inhibition of ergosterol synthesis in cultures of Candida albicans, ATCC E-10.231, at 6 x 10(5) cells/ml grown aerobically at 37 degrees C, using various concentrations of sertaconazole. Sertaconazole inhibited the ergosterol synthesis with IC50 = 115 nmol/l. The results show that one of the mechanisms of action of sertaconazole consists in the inhibition of ergosterol synthesis. PMID- 1627191 TI - Direct membrane-damaging effect of sertaconazole on Candida albicans as a mechanism of its fungicidal activity. AB - The direct action of 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1 yl)ethoxy- methyl]benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2) on the membrane integrity of C. albicans is studied by quantifying the leakage of intracellular adenosine triphosphate (ATP) into the medium as an index of the changes in membrane permeability and integrity and cell viability of the culture used. Sertaconazole caused a dose-dependent decrease in intracellular ATP after only 10-min exposure and a concomitant significant increase in extracellular ATP. This behaviour is characteristic of antifungals which are fungicidal as a result of a direct membrane damage. Thus sertaconazole, in addition to the mechanism of action responsible for its fungistatic activity (inhibition of ergosterol synthesis), has a second mechanism of action providing a significant fungicidal activity due to direct cell membrane damage. PMID- 1627192 TI - Acute toxicity studies of sertaconazole. AB - The acute toxicity of 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1 yl)ethoxy- methyl]benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2) was evaluated in mice and rats after single administration by oral, subcutaneous and intraperitoneal routes. The latter intended to ensure maximum blood levels, since intravenous route was unfeasible due to drug insolubility in water. LD50 was indeterminable (greater than 8000 mg/kg) in all routes of dosing. According to these results, and having furthermore proved the absorption of the test substance after oral administration, sertaconazole was concluded to be very safe in the event of overdose or accidental ingestion. PMID- 1627193 TI - Subacute toxicity and maximum tolerable dose of sertaconazole in repeated administration studies. AB - 28-Day oral and dermal subacute toxicity studies of 7-chloro-3-[1-(2,4 dichlorophenyl)-2-(1H-imidazol-1-yl) ethoxy-methyl] benzo [b] thiophene (sertaconazole, FI-7045, CAS 99592-32-2), were carried out. The oral studies included the evaluation of subacute toxicity in rat (dose levels of 50, 150 and 300 mg/kg) and maximum tolerable dose in repeated administration in ferrets (consecutive dose levels in accordance with a geometric progression of 50, 75, 112.5, 168 and 250 mg/kg), which were the animal species intended for chronic toxicity studies. The dermal studies included the evaluation of subacute toxicity in rats and rabbits (1 ml/kg of a 2% cream). The results, in general, have shown low toxic effects, which can be summarized as a slight non-significant hepatomegalia in the rat with increased gamma-GTP and alkaline phosphatase values and a high urinary pH value; no histopathological changes were observed. These effects are characteristic of azole derivatives and are therefore common to other antifungals with this chemical group. PMID- 1627194 TI - Chronic toxicity studies of sertaconazole after oral administration to rats and ferrets. AB - Six-month chronic oral toxicity studies of 7-chloro-3-[1-(2, 4-dichlorophenyl)-2 (1H-imidazol-1-yl)ethoxy-methyl] benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2) were carried out in rats and ferrets. The dose levels used were 50, 150 and 300 mg/kg in rats and 50, 150 and 250 mg/kg in ferrets. There was no mortality associated with the drug in either of the two species. The results obtained show that the toxic effects may be summarized as a smaller body weight increase in rats at 150 and 300 mg/kg and in male ferrets at 250 mg/kg. Food consumption decreased significantly in rats at 300 mg/kg, and was not proportional to the doses of 150 and 50 mg/kg. In serum biochemistry, increases in alkaline phosphatase in rats, ALT in male ferrets at 150 and 250 mg/kg and AST only at 250 mg/kg were observed. BUN increased at 150 and 250 mg/kg in ferrets. PMID- 1627195 TI - Reproduction toxicity of sertaconazole. Segment II (teratology) and Segment III (peri-postnatal toxicity). AB - The reproduction toxicity of 7-chloro-3-[1-(2,4-dichlorophenyl)-2- (1H-imidazol-1 yl)ethoxy-methyl]benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2) (50, 100 and 150 mg/kg by oral route) has been investigated by performing two studies: the embryotoxicity or teratology study in rats and rabbits, and the peri postnatal toxicity study in rats. According to the results obtained from the embryotoxicity studies, there was no maternal toxicity in either of the two species studied. The only embryofoetal abnormalities with statistical and toxicological significance were observed at the dose of 150 mg/kg in the teratology study on rabbits: hepatomegalia, pericardial oedema and peritoneal and hepatic haemorrhages. The results of the peri-postnatal study showed that the only maternal effect relating to the drug was an increase, proportional to the dose, in the weight of the ovaries, which was significant at the dose of 150 mg/kg. With reference to the offspring, only a reduction in the viability index at 150 mg/kg was observed. The non observed effects level (NOEL) for all three studies can be estimated at 100 mg/kg. PMID- 1627196 TI - Genotoxicity studies on sertaconazole. AB - A series of 6 studies has been performed to evaluate the potential genotoxic effect of 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H- imidazol-1-yl)ethoxy methyl]benzo[b]thiophene (sertaconazole, FI 7045, CAS 99592-32-2). From these studies, the reverse mutation assay on Salmonella typhimurium, sex-linked recessive lethal mutations on Drosophila and genetic mutations in cultured mammal cells allowed to study the genetic mutations in prokaryotes and eukaryotes. In vitro and in vivo chromosomal aberrations were studied using human lymphocytes cytogenetic test, micronucleus test and sister chromatid exchange test. The results obtained in these studies, which are complemented one another, demonstrated that sertaconazole did not induce any signs of promutagenic, mutagenic or clastogenic activity or interference with the chromosomal segregation process. PMID- 1627197 TI - Dermal tolerance and phototoxicity studies of sertaconazole. AB - The local dermal tolerance of 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H- imidazol 1-yl)ethoxy-methyl]benzo[b] thiophene (sertaconazole, FI 7045, CAS 99592-32-2) was evaluated in hairless rats and albino rabbits. Test substance was applied in 2% powder (0.5 g), gel (0.5 ml) and solution (0.5 ml) formulations to rats (this is the concentration intended for the pharmaceutical preparation) and in 6% cream (0.5 ml) to rabbits (this concentration was used to estimate an overdose maximal effect). After 3- and 24-h exposure of the test substance to animals, they were observed for erythema and oedema. Sertaconazole may be considered as non irritant, since its primary irritation index was less than 0.5 in all the tests. A phototoxicity study was also carried out on guinea pigs with 1 ml 2% cream per animal, compared with psoralene as a positive control. Sertaconazole did not present any risk, since the phototoxicity level reached was null, with 2 being the minimum value considered as having toxic significance. PMID- 1627198 TI - Pharmacokinetic evaluation of labelled sertaconazole after dermal application. AB - 14C-labelled 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy methyl] benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2) was administered systemically (i.v. route) and topically (dermal route) in different formulations at doses of 10 mg/kg to hairless Sprague-Dawley rats. Determination of plasma and liver levels of radioactivity demonstrated that the dermal application of sertaconazole induced very low systemic absorption with all the formulations used: 1.47% for sertaconazole cream, 1.97% for sertaconazole solution, 0.665% for sertaconazole powder and 0.885% for sertaconazole gel. Calculations were made from the areas under plasma levels curves of each topical administration in comparison with intravenous administration. Significant radioactivity levels were found in the liver, which was consistent with a high hepatic metabolization and faecal excretion of the substance. However, the liver levels after topical application were virtually insignificant in comparison with the levels in the same organ obtained after intravenous administration. PMID- 1627199 TI - Pharmacokinetics and tolerance of sertaconazole in man after repeated percutaneous administration. AB - The local and systemic tolerance of 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H- imidazol-1-yl)ethoxy-methyl]benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592 32-2) 2% cream was studied in healthy volunteers after cutaneous application in an increasing-dose schedule during 13 days. Blood and urine samples were collected after the application of 16 g of cream. Percentage of absorption was determined in eight 3 x 3 cm areas of the volar arm skin after 2 mg cream topical application. No changes on vital signs (blood pressure, heart rate and body temperature) or in the ECG were found during the trial. Sertaconazole did not produce skin irritation nor systemic side effects. Sertaconazole was not detected in either the serum and urine samples obtained. The percentage of cutaneous absorption at 24 h after administration reached 72% of the applied dose. PMID- 1627200 TI - Study on the sensitizing capacity of the new antimycotic sertaconazole in the treatment of cutaneous mycoses. AB - The sensitizing capacity of 7-chloro-3-[1-(2,4-dichlorophenyl)-2- (1H-imidazol-1 yl)ethoxy-methyl]benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2) was studied in a randomized double-blind clinical trial in 78 atopical volunteers of both sexes. Sertaconazole in 2% dermatological cream form was compared with 5 other commercially available antimycotics (econazole, ketoconazole, bifonazole, clotrimazole and miconazole), using the excipient of the cream without sertaconazole and 2% sertaconazole in vaseline as controls. At the end of the trial, only miconazole showed a positive allergy (vesiculation) in two of the 78 individuals studied. The other substances did not demonstrate any sensitizing capacity, including sertaconazole and its excipient. This trial showed that sertaconazole in 2% dermatological cream form does not possess a sensitizing capacity for causing contact dermatitis which confirmed its excellent safety in topical use. PMID- 1627201 TI - Phase II study of the therapeutic efficacy and safety of the new antimycotic sertaconazole in the treatment of superficial mycoses caused by Candida albicans. AB - The activity of 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy methyl] benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2) was studied in a randomized parallel double-blind clinical trial on 20 patients suffering from superficial mycosis caused by Candida albicans (confirmed microscopically and microbiologically). The patients were divided into two groups; one received sertaconazole 1% cream (10 patients) and the other received sertaconazole 2% cream (10 patients), over a period of 28 days. Clinical, microscopic and microbiological parameters were evaluated. Analytical parameters such as the appearance of possible undesirable effects (both local and general) were also monitored. The cure was total for 19 out of the 20 patients, demonstrating high efficacy. There were no relapses of infection in any of the cured patients. No local or general effects were recorded during the trial. The analytical parameters remained within normal limits. The clinical and microbiological cure, absence of relapses and the non-existence of local and general undesirable effects indicate that sertaconazole may represent an important advance in the therapy of superficial mycosis caused by Candida albicans. PMID- 1627202 TI - Therapeutic efficacy and safety of the new antimycotic sertaconazole in the treatment of cutaneous dermatophytosis. AB - 7-Chloro-3-[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy-methyl] benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2) is a new antimycotic which, in experimental infection studies, proved to possess potent antifungal activity. In a randomized, parallel, double-blind trial, the activity of sertaconazole cream was studied in 20 patients suffering from superficial mycoses caused by dermatophytes, confirmed by microscopic examination (KOH) and culture test. The patients, who were included in accordance with microbiological, microscopic and clinical criteria, were divided into two groups of 10 and were treated with sertaconazole 1% or sertaconazole 2% (cream) twice a day for 28 days. Both treatments achieved a total cure of the disease, with a cure being reached in a shorter time in the group of patients treated with sertaconazole 2%. No undesirable effects or statistically significant changes in the blood tests conducted at the end of the trial were observed. The results of the trial show that sertaconazole 2% cream is more effective. In view of the advantages offered by topical therapy over systemic therapy and of the good results obtained in patients with dermatophytosis, sertaconazole may represent an important advance in the therapy of superficial dermatophytoses. PMID- 1627203 TI - Therapeutic efficacy and safety of the new antimycotic sertaconazole in the treatment of Pityriasis versicolor. AB - The activity of 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl) ethoxy methyl]benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32,2) was studied in a randomized parallel double-blind clinical trial on 21 patients suffering from Pityriasis versicolor (confirmed by KOH microscopic examination and exploration with Wood's light). The patients were divided into two treatment groups: one with 11 patients receiving sertaconazole 1% cream and the other with 10 patients receiving sertaconazole 2% cream. The cream was applied twice a day during 4 weeks. The data were assessed clinically and microscopically (optical and fluorescence). All the patients were cured (100% cure), showing excellent efficacy. A check-up performed after the end of the treatment showed no relapses of infection. The drug safety was optimum, since no local or general undesirable effects were recorded, nor were there any changes in the analytical parameters studied in the 21 patients. Because of its high antifungal activity and excellent safety, sertaconazole represents an important advance in the topical therapy of this disease. PMID- 1627204 TI - Multi-centre double-blind trial on the efficacy and safety of sertaconazole 2% cream in comparison with miconazole 2% cream on patients suffering from cutaneous mycoses. AB - The efficacy and tolerance of 7-chloro-3-[1-(2,4-dichlorophenyl)-2- (1H-imidazol 1-yl)ethoxy-methyl]benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2) 2% dermatological cream in two daily applications compared with miconazole 2% cream in two daily applications were studied on 631 patients suffering from superficial cutaneous mycosis (sertaconazole n = 317, miconazole n = 314), in a double-blind, controlled multicentre trial with parallel groups. The therapeutic efficacy was evaluated by clinical assessment of the improvement of the lesion and symptoms, a microscopic test on the presence of hyphae or mycelia in the affected area and a culture test on the presence of active infection. Tolerance and safety were evaluated by a general blood analysis and interrogation of the patient on adverse effects. The rate of clinical cures for both treatments at the end of the follow up was 95.6% for sertaconazole and 88.1% for miconazole, with the difference being statistically significant. In the comparative analysis of the actuarial curve, it was observed that the patients treated with sertaconazole were cured earlier and in a higher proportion than those treated with miconazole, with the difference being significant. The negative result of the microscope examination and culture test confirmed the superiority of sertaconazole over miconazole, already after 14 days of treatment. At the end of the follow-up, 98.6% of the patients in the sertaconazole group obtained a negative culture test result, as opposed to 91.7% in the miconazole group, with the difference being highly significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627206 TI - Nutrition and inflammatory events: highly unsaturated fatty acids (omega-3 vs omega-6) in surgical injury. AB - Given the poor prognosis and high cost of care for patients with acute inflammatory responses (often leading to organ failure and/or allograft rejection), immunomodulation of this hyperresponse represents an important priority for research in nutritional medicine. The primary goal of nutritional support in inflammatory disease is to provide adequate energy, particularly through use of novel lipids (to alter eicosanoid pathway toward a more regulated inflammatory state), and protein to meet endogenous requirements for tissue repair IL-1 production, and restored cellular function, thus preventing secondary infection (52). Manipulation of macrophage eicosanoid production by use of omega 3 PUFA may reduce the cellular immune response (by competing with arachidonic acid, which produces inflammatory eicosanoids of the 2- and 4-series), whereas inclusion of MCT found in coconut oil may lower the arachidonic acid content of membrane phospholipids. As more data are obtained on the use of such tailored therapies in critically ill patients, a new generation of parenteral and enteral diets will be developed to reduce inflammation and immune dysfunction. PMID- 1627205 TI - Roles of a 106-bp origin enhancer and Escherichia coli DnaA protein in replication of plasmid R6K. AB - A dnaA 'null' strain could not support replication of intact plasmid R6K or derivatives containing combinations of its three replication origins (alpha, gamma, beta). DnaA binds in vitro to sites in two functionally distinct segments of the central gamma origin. The 277-bp core segment is common to all three origins and contains DnaA box 2, which cannot be deleted without preventing replication. Immediately to the left of the core lies the 106-bp origin enhancer, which contains DnaA box 1. When the origin enhancer is deleted, the core alone can still initiate replication if levels of wt pi protein are decreased or if copy-up pi mutant proteins are provided in trans. DnaA does not effect expression of R6K replication initiator protein pi, although several DnaA boxes were identified in the coding segment of the pir gene, which encodes pi. Together these data suggest that a single DnaA box, 2, is sufficient for initiation from the gamma origin and might be sufficient for initiation from the gamma origin and might be sufficient and required for the activity of the alpha and beta origins as well. Implications of the DnaA protein binding to two domains of the gamma origin and the role of the 106-bp origin enhancer in replication are discussed. PMID- 1627207 TI - Diminution in size of a fetal intrathoracic mass: caution against aggressive in utero management. AB - Space-occupying lesions within the fetal thorax are associated with poor perinatal outcome. Therefore some investigators have suggested in utero treatment. We describe a case of a fetus with a large intrathoracic mass that was noted to decrease markedly in size as gestation advanced. This case cautions against aggressive antenatal treatment. PMID- 1627208 TI - Effect of daily immersion on the edema of pregnancy. AB - To evaluate whether pregnant women become refractory to the effects of immersion, we studied 11 healthy women from 26 to 38 weeks' gestation, immersed in 34 degrees C shoulder-deep water for 4 or 5 consecutive days. The daily immersion diuresis showed no change throughout the study (p = 0.98: mean, 145 ml, 159 ml, 159 ml, 173 ml, 184 ml, day 1 through day 5, respectively). The range of urine volumes was broad, 35 to 675 ml, depending on the subject's degree of edema. Immersion produced a significantly larger diuresis compared with preimmersion values, 162 ml versus 110 ml. Maternal blood pressure and heart rate consistently fell during immersion, and this effect was maintained for each day studied. The subjects' hematocrit, hemoglobin, and total protein were unchanged from a preimmersion sample on day 1 to a postimmersion sample on the last day of the study. The results of this study indicate that pregnant women do not become refractory to the hemodynamic and diuretic effects of immersion. PMID- 1627209 TI - Response of fetal heart rate to scalp stimulation related to fetal acid-base status. AB - The correlation of the response of the fetal heart rate (FHR) to scalp stimulation and the acid-base status of the fetal scalp blood (FSB pH) was studied in 104 term fetuses during labor. The mean FHR was determined for the 5 minute period before the preparation for fetal scalp blood pH determination and 1 minute following FSB pH. The analysis was performed for three pH groups: (a) Normal (pH more than 7.25, = 73); (2) preacidotic (pH 7.20 to 7.25, = 16); and (3) acidotic (pH less than 7.20, = 15). The pH was confirmed at delivery by determination of umbilical cord blood acid-base status. Regression analysis of the number of fetuses responding by changing their heart rate against time was significant only for the nonacidotic fetuses. There was no significant difference in the number of subjects whose mean FHR increased, decreased, or remained unchanged between the three pH groups. Furthermore, there was no difference between the three pH groups in the number of fetuses who demonstrated significant mean heart rate changes (p less than 0.05) following the stimulation compared to those who did not. Further analysis between fetuses in the three pH groups who increased FHR 15 beats/min or more following stimulation did not discriminate between groups. We conclude that scalp stimulation results in a FHR response in all three pH categories. However, the net change in the mean heart rate following the stimulation may be negative or positive. The magnitude and the direction of this change in FHR is not significantly related to FSB pH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627210 TI - Serum erythropoietin quantitation in pregnancy using an enzyme-linked immunoassay. AB - During normal pregnancy there is a decrease in the hematocrit due to a disproportionate increase in the blood volume compared with the red cell mass. Using a new enzyme-linked immunoassay (Amgen Diagnostics), serum erythropoietin was quantified in normal nonanemic pregnancies throughout gestation and in third trimester anemic patients. We found that the mean hematocrit in normal pregnancy reached a nadir late in the second trimester and the serum erythropoietin plateaued at a 50% increase. Those pregnancies complicated by anemia defined by a hematocrit less than 30 vol% demonstrated a statistically significant increase in serum erythropoietin above those not anemic. PMID- 1627211 TI - Assessment of thermal conditions in neonatal care: use of a manikin of premature baby size. AB - A thermal manikin of the size of a 1 kg premature baby has been constructed. The nonevaporative heat loss from eight different regions and the total heat loss were measured. The measurements of heat loss have high repeatability and the values are in good agreement with measurements of dry heat loss for premature babies, using indirect calorimetry. The heat losses from the manikin in a single walled, air-heated incubator and on a recently described heated, water-filled mattress have been compared. The total heat loss was found to be 20 to 30 W/m2 with both methods at ambient temperatures between 15 degrees and 25 degrees C. Treatment on a heated, water-filled mattress provides a means of direct conductive heat input to the baby, with a conductive heat transfer coefficient of 0.4 W/degrees C or 21 W/m2 degrees C. The thermal manikin appears to provide an accurate method for assessment of the thermal conditions in neonatal care. PMID- 1627213 TI - Umbilical artery and uteroplacental velocimetry in pregnancies complicated by idiopathic low birthweight centile. AB - Umbilical artery and uteroplacental Doppler flow velocity waveforms were studied in 35 pregnancies complicated by idiopathic low birthweight centile. Thirty fetuses (86%) were below the 5th centile birthweight for gestation. Fifteen (43%) had an abnormal umbilical artery systolic to diastolic ratio. Uteroplacental waveforms were recorded in 29 of the 35 pregnancies and five (17%) showed an abnormal systolic to diastolic ratio. Abnormal uteroplacental systolic to diastolic ratios were associated with a significantly earlier gestational age at delivery and significantly more cesarean sections for fetal distress compared with normal uteroplacental systolic to diastolic ratios (p less than or equal to 0.01). The absence of umbilical artery end-diastolic frequencies was associated with a significantly earlier gestational age at delivery compared with the presence of umbilical artery end-diastolic frequencies (p less than 0.005). No differences in pregnancy outcome were observed comparing normal with abnormal amniotic fluid volume assessment. These findings suggest that Doppler studies may be useful in estimating the risk of adverse perinatal outcome for small for gestational age fetuses with no identifiable cause. PMID- 1627212 TI - Zidovudine pharmacokinetics during pregnancy. AB - As the indications for zidovudine (ZDV) treatment in human immunodeficiency virus infected individuals expand, we anticipate an increased use of this drug during pregnancy. We report pharmacokinetics data from a patient studied both in the third trimester and intrapartum. ZDV peak-plasma levels and serum half-lives were comparable to nonpregnant adults. High concentrations of ZDV and its glucuronide metabolite were found in umbilical cord blood and in amniotic fluid. PMID- 1627214 TI - Treatment of neonatal renovascular hypertension with intravenous enalapril. AB - Hypertension in the neonate is commonly related to renal disease. More specifically, renovascular hypertension in neonates is often associated with the placement of a umbilical artery catheter. Many medications, including angiotensin converting enzyme (ACE) inhibitors, have been used in the treatment of neonatal hypertension. Captopril, an ACE inhibitor, is an oral agent that is effective in renovascular hypertension. We describe the use of intravenous enalapril, another ACE inhibitor, in successfully treating severe renovascular hypertension refractory to standard medical therapy in two term neonates. PMID- 1627215 TI - Perinatal outcome of twin pregnancies complicated with preeclampsia. AB - Twenty-five mild and 19 severe preeclampsia cases in twin pregnancies (12.5%) were compared to 44 matched for gestational age controls. All three groups were similar with respect to maternal age, intertwin birthweight differences, and rates of abdominal deliveries and low (less than 7) 5-minute Apgar scores. The frequency of primiparas in the severe preeclampsia group was significantly higher compared with controls (p less than 0.03). Severe preeclampsia patients delivered at a significantly earlier gestational age (p less than 0.005) and had a significantly lower mean twin birthweight (p less than 0.003) compared with the mild preeclamptic group. The mean twin birthweight of the severe preeclamptic cases was also significantly lower compared with that of controls. All three neonatal deaths occurred in severely discordant second twins born to severe preeclamptic patients. It is concluded that adverse perinatal outcome is associated with severe but not with mild preeclampsia in twin gestations. PMID- 1627216 TI - Use of percutaneous silastic central venous catheters in neonates and the management of infectious complications. AB - A prospective study of 35 patients in the neonatal intensive care unit was conducted to examine the safety and feasibility of percutaneous Silastic central venous catheters for the provision of prolonged parenteral alimentation. Particular attention was directed to the possibility of maintaining these lines through intercurrent episodes of infection. Catheters were placed in 34 infants (97%). At the time of insertion, 21 patients (62%) weighed less than 1000 gm and 13 patients (38%) weighed less than 750 gm. The average duration of catheterization was 32.0 +/- 18.2 (SD) days; 19 patients (56%) had lines in place for more than 30 days. Mechanical difficulties complicated the course of five patients (15%). Four cases of bacteremia were identified; this represents 3.7 infections/1000 days of catheter use. All infections were caused by methicillin resistant staphylococci. Two patients required catheter removal to clear their infection, but in two of the four bacteremic patients, the infection was cleared and the line was sterilized by the administration of antibiotic therapy through the central catheter. We conclude that Silastic central venous catheters can be used safely to deliver intravenous nutrition to extremely small preterm infants over a prolonged period of time, and in carefully selected patients, successful treatment of complicating infections may be achieved without catheter removal. PMID- 1627217 TI - Sucking patterns of neonates during bottle feeding: comparison of different nipple units. AB - The present study was designed to compare the sucking pattern of term and preterm infants during bottle feeding with different types of nipple units (Enfamil single-hole nipple units for term and preterm infants and SMA Nuk nipple units). In addition, the sucking pattern of term neonates during a feeding regimen commonly used in many feeding studies was evaluated (reservoir nipple system). In this system milk flows from a reservoir through a tube and depends on the sucking pressure generated by the infant. Only the Enfamil single-hole nipple units for term and preterm infants were compared in preterm infants. No significant difference in sucking frequency was observed in term neonates with different types of nipple units. Although the mean sucking pressures generated tended to be less among nipple units with higher flow, these differences were not statistically significant. Similarly, no significant difference in total sucking or feeding time was observed among the three nipple units tested. Sucking pressures generated by term infants were significantly less when milk flow was increased markedly utilizing the reservoir system. In preterm infants no differences in sucking frequency, sucking pressure, mean flow, or total feeding time were observed when sucking patterns with term and preterm nipple units were compared. Implications of these findings in feeding neonates are discussed. PMID- 1627218 TI - Nicotine-induced changes in the cerebral circulation in ovine fetuses. AB - Pulsed Doppler ultrasound was used to investigate fetal and maternal ovine circulation in 16 ewes. Resistance index (R) was measured at the following sites: umbilical, fetal cerebral, and uterine arteries. Measurements were performed at days 80, 100, and 130 of gestation, day 0 being the day of mating. Normal ranges of the Doppler indices were delimited on the six control ewes. Five ewes were treated by intramuscular injection of 10 mg of nicotine 5 days per week and five others received placebo injections. No difference was found on the Doppler indices between the control group and the placebo group. The cerebral indices did not differ in the three groups at days 80 and 100 but were significantly higher at day 130 in the nicotine group in comparison to the two others (p less than 0.01). The umbilical indices were slightly elevated at days 80 and 130 in the nicotine group. No significant difference was found on the uterine indices at any of the three stages of gestation whatever the treatment. In the control and placebo groups the ewes delivered in the normal ranges of gestation length. In these groups 2 of 20 lambs (10%) died at birth. In the nicotine group 2 ewes delivered prematurely and 8 of the 13 lambs (62%) were stillborn. In conclusion, repeated nicotine injections induce vasoconstriction on the umbilical and cerebral arteries of the fetus at the end of the gestation and are associated with poor perinatal outcome. PMID- 1627219 TI - Periosteal reaction induced by prostaglandins. AB - Prostaglandin administration is the main therapy for ductal-dependent congenital heart disease prior to definitive therapy. We report a case in which tetralogy of Fallot and Noonan syndrome were diagnosed, complicated by small pulmonary arteries, which occasioned a delay in surgery. Treatment was started with prostaglandins, which were given for a total of 2 months, and a diffuse periosteal reaction occurred secondary to the administration of intravenous prostaglandin E1. PMID- 1627220 TI - Does prenatal care decrease the incidence and cost of neonatal intensive care admissions? AB - This study was conducted to examine the potential effects of expanded Medicaid coverage for low income women. Statewide birth data for 1983 to 1985 were examined to determine the relationship between prenatal care and admissions to neonatal intensive care units (NICUs) and the costs of this care. An NICU sample was constituted from infants who were discharged live following more than 7 NICU days, were referred to an out of state tertiary center, or died following NICU admission. Inadequate care (no prenatal care, only last trimester care, or less than five visits) was received by 11% of the total birth cohort and by 18% of the infants in the NICU sample (p less than 0.001). Infants with inadequate care had a NICU admission rate of 5.10% versus 2.86% for those with adequate prenatal care (p less than 0.001). The hospital billings for infants in the NICU sample with inadequate care were significantly higher than were those for infants with adequate care (p less than 0.05). Assuming that economic resources limit access to prenatal care, the projection can be made that had all women with inadequate prenatal care received Medicaid-covered adequate prenatal care, expenditure for this care would yield more than a two to one return in savings in NICU costs. PMID- 1627221 TI - Effect of labor and delivery on neonatal polymorphonuclear leukocyte number and function. AB - The ability of the neonate to mount an adequate polymorphonuclear leukocyte (PMN) response, either quantitatively or functionally, is impaired. To assess whether neonatal PMN number and function are altered by labor and delivery, three groups of infants were studied: cesarean section without labor (10), cesarean section after labor (10), and vaginal delivery (11). PMN counts were higher in the groups undergoing labor (p less than 0.01) compared with the cesarean section without labor group. Similarly, the labor groups had evidence of complement activation (increased C3a desarg) compared with the cesarean section without labor group. No differences were noted between the groups in measures of PMN motility (chemokinesis or chemotaxis) or PMN degranulation (plasma lysozyme), suggesting that normal labor and delivery does not contribute to the general PMN dysfunction of the neonate. PMID- 1627222 TI - Seroprevalence of human immunodeficiency virus type 1 among pregnant women. AB - Five (0.74%) of 678 women delivering in 1985 at a tertiary referral hospital for high-risk pregnancies and 16 (1.34%) of 1198 women visiting an urban prenatal obstetrics clinic in 1986-1987 had serologic evidence of human immunodeficiency virus type 1 (HIV-1) infection. Unlinked testing (removal of personal identifiers from the blood specimen and the epidemiologic data sheet) of residual serum from hepatitis B virus serologic testing was used. Neither age, marital status, payor status, nor serologic markers of hepatitis B virus infection was useful in identifying women at risk for HIV-1 infection. As a result of these data, we have initiated a program in which counseling is offered to all women and testing for those who consent. Unlinked testing of women who refuse consent is performed for epidemiologic purposes. This will allow us to continue to plan for health care resource needs and to track the course of the epidemic in various subgroups of pregnant women. PMID- 1627223 TI - Respiratory complications associated with cryotherapy in premature infants. AB - We reviewed the frequency of respiratory complications associated with cryotherapy in 14 premature infants who underwent 17 cryotherapy procedures. Five of the procedures were performed on infants already being mechanically ventilated. Two of these infants required increased ventilatory support during and following the procedure for decreased spontaneous respirations. For the 12 procedures performed on 11 infants who were not being mechanically ventilated at the time of cryotherapy, four infants had no complications, three infants had minor respiratory deteriorations, and five infants required positive pressure ventilation for severe apnea and bradycardia episodes (one just after narcotic administration, four during the procedure). Excluding the three infants (five procedures) who were already receiving mechanical ventilation at the time of cryotherapy, the infants who had severe apnea requiring the initiation of positive pressure ventilation weighed less and were younger than those infants not having a serious respiratory complication (p less than 0.05). PMID- 1627224 TI - A case of deletion of the short arm of chromosome 10 with severe hearing loss and brainstem dysfunction. AB - A male newborn infant with a deletion of the short arm of chromosome 10p 14 was described. In addition to the typical clinical features, electrophysiologic studies showed brainstem dysfunction and severe hearing loss when examined with auditory brainstem response and photopalpebral reflex. These electrophysiologic studies may be of benefit for early evaluation of brainstem functions and hearing ability of the patients of such chromosomal aberration and may also be useful predictors of psychomotor development. PMID- 1627225 TI - In utero conversion of supraventricular tachycardia with digoxin and procainamide at 17 weeks' gestation. AB - The earliest reported case of fetal supraventricular tachycardia at 17 weeks' gestation causing hydrops fetalis is presented. Maternal treatment with digoxin and procainamide successfully cardioverted the fetus with resolution of the hydrops. Using this combination, sinus rhythm was maintained until term. PMID- 1627226 TI - Comparison of rapid tests for detection of group B streptococcal colonization. AB - Accurate rapid detection of maternal lower genital tract colonization with group B streptococci (GBS) in high-risk patients is essential for selective institution of intrapartum antibiotic treatment to reduce neonatal GBS infection. In this study, pure GBS isolates were used to evaluate five commercially available rapid tests in terms of speed, ease of use, and sensitivity. The products tested were Directigen, Equate, Bactigen, PathoDx, and Phadebact. Although each test could be performed relatively quickly, the ease of performance and level of sensitivity (10(5) to 10(8) CFU/ml) varied markedly. Quantitative cultures obtained from 17 known GBS carriers showed concentrations ranging from less than 10(2) to greater than 10(8) CFU/gm of vaginal material. Since only 40% of the women had greater than or equal to 10(5) CFU/gm of vaginal material, it appears that many colonized women would not be identified by these rapid tests. PMID- 1627227 TI - Prenatal care revisited: does it make a difference? PMID- 1627228 TI - Magnetic resonance imaging and computed tomography scan for the diagnosis of acute fatty liver in pregnancy. PMID- 1627229 TI - Low-dose-aspirin: treatment of the imbalance of increased thromboxane and decreased prostacyclin in preeclampsia. PMID- 1627230 TI - Woman with AIDS presented for elective termination of pregnancy. PMID- 1627231 TI - Detection of cell-mediated immunity in type I diabetes mellitus. AB - Type I insulin dependent diabetes mellitus (IDDM) is thought to result from chronic, cell-mediated, 'autoimmune' islet damage. Antibody testing is extensively used to define and follow the pre-diabetic population. However, the assay for cell mediated immunity (CMI) should be more predictive of impending disease. This report shows that it is possible to detect human islet reactive CMI in the IDDM patient. Groups of athymic CD-1 nu/nu mice were injected intraperitoneally with either mononuclear blood cells (MBCs) or plasma from 10 newly diagnosed Type I diabetic patients and 10 normal control subjects. Both glycemic control and histopathology were used to assay islet specific CMI in diabetic individuals. None of the injected mice showed any impairment of glycemic control. However, MBCs from six of 10 diabetic patients, but from none of the 10 normal subjects, induced significant mononuclear cell infiltrate in the pancreas of the recipient mice (P = 0.005). The infiltrate was focused on the islet tissue and no damage was seen in control tissues. No histological abnormalities were observed when plasma was transferred. We conclude that cellular reactivity seen in this model is tissue specific and disease associated. Our findings provide evidence that CMI to human islet tissue can be detected in IDDM patients. PMID- 1627232 TI - Production of a human monoclonal anti-epithelial cell surface antibody derived from a patient with pemphigus vulgaris. AB - The production of monoclonal autoantibodies derived from individuals with autoimmune diseases constitutes a powerful tool to analyse an autoimmune process at both the antigen and antibody levels. We established a human anti-epithelial cell surface monoclonal antibody by applying hybridoma technology using peripheral blood lymphocytes from a patient with pemphigus vulgaris using a heteromyeloma as the fusion partner. The F12 monoclonal antibody displays four major characteristics: (1) it belongs to the IgM, kappa class; (2) it binds to the cell surface of stratified squamous and simple epithelia; (3) it recognizes an antigenic determinant associated with the desmosomal complex as demonstrated by indirect immunoelectron microscopy; (4) by immunoblotting analysis, it reacts with a 185 kDa polypeptide which was also recognized by a few pemphigus vulgaris sera. Although the F12 monoclonal antibody does not have the immunochemical properties of classical pemphigus vulgaris autoantibodies, several arguments suggest its relevance to the pemphigus vulgaris autoimmune response and, therefore, the heterogeneity of the antigen/antibody systems involved in this autoimmune disorder. PMID- 1627233 TI - SRI 62-834, a cyclic ether analogue of the phospholipid ET-18-OCH3, displays long lasting beneficial effect in chronic relapsing experimental allergic encephalomyelitis in the Lewis rat. Comparison with cyclosporin and (Val2) dihydrocyclosporin effects in clinical, functional and histological studies. AB - The therapeutic effect of the ether phospholipid SRI 62-834, which lacks the characteristics of an immunosuppressive agent, was compared with those of two immunosuppressive drugs, cyclosporin and valine2-dihydrocyclosporin, in a rat model of chronic relapsing experimental allergic encephalomyelitis (CR-EAE). Drug treatment was initiated at the beginning of the first spontaneous remission on day 15 and was discontinued on day 31. Whereas the untreated rats experienced two paralytic relapses around days 21 and 31, the progression of CR-EAE was prevented during the period of drug administration. Protection with both cyclosporin and its derivative was complete, but SRI 62-834 only attenuated the clinical disease. The absence of paralytic symptoms was reflected by a distinct reduction in mononuclear cell infiltration in the central nervous system at days 21 and 31 in treated animals. The main difference between the two drug classes became apparent after withdrawal of therapy. Discontinuation of SRI 62-834 resulted in a long lasting beneficial effect, with the rats remaining clinically normal and showing no histopathological changes. However, cyclosporin only delayed the clinical symptoms which reappeared after cessation of treatment. The exacerbated paralytic relapse, which followed about 1 week later and was associated with severe perivascular cell infiltrates and tissue destruction, subsequently became chronic in several animals. By contrast, withdrawal of valine2-dihydrocyclosporin partially prevented disease relapse and markedly reduced severity of symptoms without progression of a chronic disease. These results demonstrate the clear differences in the mode of action of these compounds in CR-EAE and suggest that SRI 62-834 could be an interesting candidate for the treatment of multiple sclerosis. PMID- 1627234 TI - Implications of modifying cardiolipin acyl composition by diet. 1. Cardiolipin acyl chain is an important determinant in the binding to antiphospholipid antibodies in SLE sera. AB - Antiphospholipid antibodies (aPL), prevalent in sera of patients with systemic lupus erythematosus (SLE), have been linked to thrombosis, thrombocytopenia, recurrent miscarriages, neurological disorders and ischemic heart disease. Most evidence suggests that phosphodiester-linked phosphate groups are the reactive epitope of cardiolipin (CL) in binding to aPL. Little attention has been given to the acyl moiety. To address this problem we have evaluated the ELISA binding of 12 highly positive IgG anticardiolipin antibody-positive SLE sera to: bovine CL (86.1% 18:2n-6), monolyso CL (MLCL; bovine CL minus 1 fatty acid), dilyso CL (DLCL; minus 2 fatty acids), tetraoleoyl CL (TOCL), myristoyl CL (MCL) and E. coli CL. The reductions in binding of the IgG aPL antibodies relative to bovine CL were as follows: DLCL 83%; MLCL 70.7%; MCL 58%; and TOCL 14% (P less than 0.05). These data suggest that the number of acyl chains and the unsaturation of the acyl chain of CL may be important determinants in the binding to aPL present in SLE sera. To investigate the nutritional relevance of this finding, we examined the incorporation of several dietary fatty acid classes into the CL pool of mice. Mice were fed diets containing n-6 (safflower oil), n-9 (olive oil) or n 3 fatty acids as either 18:3n-3 (linseed oil) or 20:5n-3/22:6n-3 (fish oil) for a 5 month period. The feeding of fish oil and olive oil resulted in replacement of a substantial portion of 18:2n-6 with 22:6n-3 or 18:1n-9, respectively. These results suggest that there may be therapeutic value in modifying the CL acyl composition by nutritional means with respect to binding to pathogenic aPL. PMID- 1627235 TI - Soluble interleukin-2 receptor and disease activity in Crohn's disease. AB - An ELISA was used to measure concentrations of soluble interleukin-2 receptor (sIL-2R) alpha chain in the sera of patients with Crohn's disease. In a group of 56 patients, serum concentrations of sIL-2R were significantly raised in patients with active disease compared with patients with inactive disease and age-matched control populations. There was a significant correlation between serum sIL-2R concentration and disease activity as assessed by the Harvey-Bradshaw index (r = +0.60; P less than 0.001) and laboratory measurements of disease activity including C-reactive protein (r = +0.79; P less than 0.001), ESR (r = +0.64; P less than 0.001) and platelet count (r = +0.533; P less than 0.001). We also found a negative correlation between sIL-2R levels and serum albumin (r = -0.66; P less than 0.001). In longitudinal studies, changes in the concentration of serum sIL-2R reflected the changes in disease activity. Soluble IL-2R, therefore, offers a new measure of disease activity in Crohn's disease with a potential advantage over other laboratory parameters currently available in that it may reflect more accurately the underlying immunopathogenic process. PMID- 1627236 TI - Warm Carolina rinse solution prevents graft failure from storage injury after orthotopic rat liver transplantation with arterialization. AB - An injury to nonparenchymal cells, characterized by loss of viability of sinusoidal endothelial cells and activation of Kupffer cells, occurs after reperfusion of livers stored for transplantation. Recently, a new solution, Carolina rinse solution, was shown to prevent reperfusion injury to endothelial cells in vitro almost completely and to improve graft survival after orthotopic rat liver transplantation (ORLT) without arterialization. ORLT with arterialization permits longer cold storage of donor livers and more closely models human surgery. Therefore, we evaluated the effects of Carolina rinse solution on graft survival after ORLT with arterialization in syngeneic Lewis rats. Just prior to implantation, donor livers stored in University of Wisconsin (UW) solution were rinsed with 30 ml of Ringer's solution, saline, or Carolina rinse solution at 1 degree-4 degrees C. In livers stored for 15 h and rinsed with Ringer's or saline solution, long-term graft survival was only 8%. Using Carolina rinse solution containing 1 mmol and 200 mumol adenosine per liter, graft survival improved to 40% and 80%, respectively. Graft survival did not improve when using Carolina rinse solution with adenosine omitted or Ringer's solution containing 200 mumol adenosine per liter. Livers were also rinsed with Carolina rinse solution containing 200 mumol adenosine per liter at 28 degrees-30 degrees C rather than at 1 degree-4 degrees C. With warm Carolina rinse solution, survival improved further to 100%, 80%, and 50% after 15, 18, and 21 h of storage. After 18 h of storage, light and electron microscopy demonstrated marked denudation of the sinusoidal lining and activation of Kupffer cells in grafts rinsed with Ringer's solution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627237 TI - Postprandial increase in serum creatinine in renal transplant recipients. AB - Daily variation in serum creatinine and the effect of a protein load was studied in 18 patients with renal transplants and in 10 healthy controls. Serum creatinine was analyzed both with a standard Jaffe method and with a specific HPLC technique. Following a protein meal, a 30% increase in serum creatinine levels was noted in both groups, but the rise in absolute terms was more prominent among the transplanted patients. Urinary excretion of creatinine did not increase in the transplanted group, indicating a reduced ability to deal with the surplus creatinine in the protein meal. It is concluded that serum creatinine levels are diet-dependent and that this variation is more pronounced when renal function is reduced. Standardized blood sampling is important when following serum creatinine in renal transplant recipients from one day to the next. PMID- 1627238 TI - Histologic resolution of documented hemosiderosis in a renal transplant recipient. A case report. AB - A 33-year-old cadaveric renal transplant recipient showed complete histologic resolution of hemosiderosis by liver biopsies obtained pre- and post transplantation. Although there have been reports in the past of progression of hemosiderosis to hemochromatosis to severe liver failure in the renal transplant population, the correlation has never been clear. This is the first case report of complete resolution of hemosiderosis as documented histologically by liver biopsies in a cadaveric renal transplant recipient. PMID- 1627239 TI - A simplified technique for hepatic revascularization of the liver graft with inadequate recipient hepatic artery. PMID- 1627240 TI - "Arterialization", "revascularization", "rearterialization"--what's in a name? PMID- 1627241 TI - Liver transplantation for arteriohepatic dysplasia (Alagille's syndrome). AB - Thirteen out of 268 children (less than 18 years old) underwent hepatic transplantation (OLT) for end-stage liver disease (ESLD) associated with arteriohepatic dysplasia (AHD). Seven children are alive and well with normal liver function. Six children died, four within 11 days of the operation and the other two at 4 and 10 months after the OLT. Vascular complications with associated septicemia were responsible for the deaths of three children. Two died of heart failure and circulatory collapse, secondary to pulmonary hypertension and congenital heart disease. The remaining patient died of overwhelming sepsis not associated with technical complications. Seven patients had a portoenterostomy or portocholecystostomy early in life; five of these died after the OLT. Severe cardiovascular abnormalities in some of our patients suggest that complete hemodynamic monitoring with invasive studies should be performed in all patients with AHD, especially in cases of documented hypertrophy of the right ventricle. The improved quality of life in our surviving patients confirms the validity of OLT as a treatment of choice in cases of ESLD due to AHD. PMID- 1627242 TI - Effect of reduced cyclosporin dosage on long-term renal allograft histology. AB - The effect of different doses of cyclosporin (CyA) on the occurrence of histological lesions in renal allograft biopsies was investigated 2 years after transplantation. Biopsy findings were compared in three different groups of patients. In group 1, patients were immunosuppressed with CyA and prednisolone according to an early, high-dosage schedule (initial CyA dose 15-17.5 g/kg body weight); in group 2, they were treated with a medium CyA dose (initial dose 12 mg/kg), together with prednisolone; and in group 3, patients were given triple drug therapy consisting of low doses of CyA (initial dose 8 mg/kg), together with both azathioprine and prednisolone. Interstitial fibrosis and tubular atrophy were common findings in all groups, and on the basis of all biopsies, no difference could be found between the groups with respect to the relative volume of the renal cortical interstitium, which was used as a quantitative parameter for interstitial fibrosis. Likewise, no difference was found with respect to serum creatinine levels. When grafts that showed signs of rejection (usually vascular rejection) in the biopsy were excluded (two in group 1, six in group 2, and ten in group 3), the mean interstitial volume was significantly lower in group 3 (triple drug therapy) than in the other groups. The serum creatinine levels were also significantly lower in group 3 than in group 1. Thus, chronic renal lesions could be ameliorated when CyA doses were lowered, but this appeared to entail an increased risk of acute or chronic vascular rejection. PMID- 1627243 TI - The use of the University of Wisconsin (UW) and Euro-Collins (EC) solutions either alone or in a combined method. AB - From June 1988 to October 1990, a total of 100 orthotopic liver transplantations (OLTs) in 91 patients were performed at the Hospital Clinic of Barcelona. Euro Collins (EC) solution was used as the flush and storage solution in 29 livers, and the University of Wisconsin (UW) solution was used in 24. A combined method, consisting of flushing and harvesting the liver with UW solution through the portal vein and with EC solution through the aorta, was used in the remaining 47 livers. Livers harvested using such a combined method showed substantially better postoperative function in terms of AST, ALT, and prothrombin activity than those harvested in EC solution alone. Although AST and ALT values were lower in patients whose livers were harvested using the combined method than with UW alone, differences were not significant. On the other hand, prothrombin activity was consistently better in the UW group. Bilirubin levels, platelet count, and bile output showed no difference among the three groups. We conclude that the combined use of UW and EC solutions for flushing and harvesting is not hazardous to human liver preservation and, in fact, may considerably reduce the amount of UW solution needed and, consequently, the costs. PMID- 1627244 TI - Effectiveness of low-dose cotrimoxazole prophylaxis against Pneumocystis carinii pneumonia after renal and/or pancreas transplantation. AB - We retrospectively examined the effectiveness of prophylaxis with cotrimoxazole in preventing Pneumocystis carinii pneumonia in recipients of kidney and combined kidney-pancreas transplants between 1985 and 1989. Cotrimoxazole prophylaxis (480 mg daily or 300 mg/m2), when used, was started within 2 months after transplantation and usually continued until 6 months after surgery. Eight (3.7%) of the 214 patients who were not given prophylaxis were infected with Pneumocystis carinii, and there were 4 fatalities (50% mortality). There were no cases among the 161 patients given prophylaxis (P less than or equal to 0.03). No serious adverse effects were noted in the prophylaxis group. It is concluded that prophylaxis against Pneumocystis carinii infection is well tolerated and should be given as soon as possible to all organ transplant recipients for at least 6 months. PMID- 1627245 TI - Chronic rejection of rat renal allograft. I. Histological differentiation between chronic rejection and cyclosporin nephrotoxicity. AB - Chronic allograft rejection is both a clinical and a histopathological diagnosis. Until recently, the histological definition of chronic renal allograft rejection was based on clinical diagnostic biopsies, where the evidence was partially obscured by recurrence of the original renal disease, and/or by administration of immunosuppressive drugs. In this communication, we present an experimental rat model for chronic renal allograft rejection, devoid of recurrence of the original disease. By comparing allografts to similarly immunosuppressed syngeneic transplants, we define which histological features should be attributed to chronic rejection and which to cyclosporin nephrotoxicity. Rat renal transplants were performed from DA (Ag-B4, RT1av1) to WF strain (Ag-B2, RT1u) or, for control, to DA strain, and immunosuppressed for 2 or 3 weeks with cyclosporin using a variety of different dosages. The animals were monitored weekly for serum creatinine levels and for blood cyclosporin concentrations, and core needle biopsies were performed on the grafts at regular intervals. At 3 months post transplantation the animals were sacrificed and a complete histopathological evaluation was performed. Thirty-one histological variables were scored blindly by two investigators and separately for the graft interstitium, glomeruli, tubuli, and the graft vasculature. The following histological alterations were significantly more prominent in allografts than in similarly immunosuppressed syngeneic transplants: the intensity of interstitial inflammation, particularly the degree of pyroninophilia within the inflammatory cell population; the extent of glomerular mesangial matrix increase, basement membrane thickening, and glomerular sclerosis; the increase in the vascular intimal thickness affecting in particular the first and second order branches of the renal artery; and the obliteration of the graft vasculature. These alterations were considered as being primarily due to chronic rejection. In contrast, the extent of interstitial fibrosis and the extent of tubular changes, including tubular epithelial vacuolation, epithelial atrophy, and tubular basement membrane changes, were not significantly different in the allografts as compared to the syngeneic controls. These alterations were attributed primarily to cyclosporin nephrotoxicity. Serial monitoring of the grafts by needle biopsies clarified the sequence of events in the development of the chronic alterations in the transplant. The first event, as expected, was tubulointerstitial pyroninophilic inflammation, resembling that of acute episodes of rejection. This was significantly stronger and appeared earlier in allografts immunosuppressed for 2 rather than for 3 weeks. Vascular alterations developed next. The last to develop were the glomerular lesions. PMID- 1627246 TI - Regulation of major histocompatibility complex (MHC) products in fresh and cultured human fetal pancreata aged 9-16 gestational weeks by gamma-interferon. AB - Immunological data on the human fetal pancreas (HFP) are mainly confined to its constitutive expression of the MHC antigens. However, cytokines, such as gamma interferon (g-IFN), released by lymphocytes during immune reactions, can induce or upregulate the expression of MHC products in allografts and alter their immunological behaviour. We investigated the effects of g-IFN on fresh and cultured HFPs aged 9-16 gestational weeks (gw). Following g-IFN stimulation of fresh HFPs, there was class I hyperexpression by the ductal cells, and some of the ductal, endothelial and islet cells also became class II+. Conventional tissue culture (5% CO2 in air at 37 degrees C) reduced the number of interstitial class II+ cells within the HFP after 1 week but was associated with de novo class I expression by some of the ductal cells. Remarkably, the changes in major histocompatibility complex (MHC) antigen expression by the ductal cells occurred earlier and were markedly enhanced when the HFPs were cultured beforehand. The number of interstitial class II+ cells in fresh and cultured HFPs was not influenced by g-IFN. The significance of these observations with regard to clinical HFP transplantation is discussed. PMID- 1627247 TI - HIV interactions with CD4: a continuum of conformations and consequences. AB - Here, Lee Eiden and Jeffrey Lifson present a model for HIV envelope glycoprotein CD4 interactions that attempts to reconcile recent, seemingly conflicting, structural, biochemical and biological observations. Central to this model is the involvement of both the CDR2-like and CDR3-like domains of CD4 in the interaction with gp120, leading to a conformational change and dissociation of gp120 from the gp120-gp41 complex. PMID- 1627248 TI - Does the HIV envelope induce a chronic graft-versus-host-like disease? AB - Evidence is accumulating that susceptibility to disease following HIV infection is genetically restricted. In addition, activation of the immune response appears to play an important role in disease progression. Here, John Habeshaw and colleagues propose that HIV envelope glycoproteins mimic foreign MHC molecules and, in doing so, stimulate alloreactive lymphocytes. This activation may explain the marked clinical and immunological similarities between chronic GVHD and AIDS. PMID- 1627249 TI - Developmental and maturational changes in human blood lymphocyte subpopulations. PMID- 1627250 TI - The role of nasopharyngeal lymphoid tissue. AB - Nasal-associated lymphoid tissue (NALT), which comprises paired lymphoid organs in the nasopharynx of rodents, is the principal mucosal lymphoid tissue of the respiratory tract. As described in this review, NALT bears certain similarities to the Peyer's patches of the intestine but the two differ remarkably in morphology, lymphoid migration patterns and the binding properties of their high endothelial venules (HEV). PMID- 1627251 TI - Uterine granular lymphocytes are activated natural killer cells expressing VLA-1. PMID- 1627252 TI - Cytokines and Alzheimer's disease. PMID- 1627253 TI - Localization of MPP+ binding sites in the brain of various mammalian species. AB - The distribution and density of 3H-MPP+ binding sites were studied by in vitro quantitative autoradiography in the brain of the mouse, rat and monkey. The highest levels of 3H-MPP+ specific binding were observed in rat brain. The substantia nigra in rat and monkey, and the anterior caudate-putamen formation in mouse and monkey showed the lowest density of autoradiographic grains. The presence of a relatively high density of MPP+ sites in the hippocampus of all species studied could be of interest to explain some effects of MPTP administration on convulsions caused by chemoconvulsants. The finding of a 60-70% reduction of 3H-MPP+ binding sites in the rat caudate-putamen, on the side of quinolinic acid infusion and no changes after 6-hydroxydopamine lesion of dopaminergic nigrostriatal neurons suggests the presence of these sites mainly on striatal cells. The results suggest that the distribution of MPP+ binding sites in brain would not seem to be related to MPTP toxicity. PMID- 1627254 TI - Release signs in Parkinson's disease with and without dementia. AB - Release signs have been described in both age-associated diseases and in the healthy elderly. We investigated the palmomental, snout, grasp, corneomandibular and glabellar reflexes in demented and non-demented Parkinson-patients compared to Alzheimer's disease and age-matched controls. The palmomental reflex and a persisting glabellar reflex were linked to parkinsonism irrespective of dementia and were found also in Alzheimer's disease. A corneomandibular reflex was observed more frequently in demented than non-demented Parkinson-patients and in Alzheimer's disease. The snout-reflex was present in nearly all individuals irrespective of diagnosis. Thus, various release signs react quite differentially to degenerative brain disease and dementia. PMID- 1627255 TI - Age influences abnormalities in striatal dopamine metabolism during and after transient forebrain ischemia. AB - Age has been found to be a significant risk factor for brain ischemia and its mortality. After cerebral ischemia, the nigrostriatal dopaminergic system undergoes selective vulnerability with necrosis of striatal neurons. To study the effect of age and transient forebrain ischemia on striatal dopamine metabolism, investigations were performed in 1-year-old (adult) and 2-year-old (aged) male Wistar rats. A 15 min period of bilateral transient incomplete ischemia (ICI) was induced, and the concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), and homovanillic acid (HVA) were measured in the striatum by means of HPLC and electrochemical detection at the end of ischemia without reperfusion, and after 1 h, 24 h, 72 h, 144 h, and 288 h of postischemic cerebral reperfusion. In normal conditions, no 3-MT was detectable in either age group studied, and no other age-related changes could be found in DA or its metabolites. During ICI, an age-related difference became obvious in the 3-MT concentration, which was higher in aged animals. In this group, DOPAC dropped and DA turnover increased. After 1 h of postischemic reperfusion, the concentrations of DOPAC and HVA, as well as the turnover rate, had increased in both age groups, whereas an increase in the DA concentration became apparent in the adult animals only. The enhancement of the concentration of both DOPAC and HVA was more marked in adult animals than in aged ones. At 24 h of postischemic cerebral reperfusion, DA concentration was still elevated in both age groups, and HVA in the 1-year-old animals only. At 72 h of postischemic cerebral reperfusion, no differences were obvious between adult experimental animals and controls, whereas the elevated DA concentration persisted in aged animals, being higher than in the control group and in the 1-year-old rats. DA turnover was reduced. Longer periods of postischemic cerebral reperfusion were not found to be followed by any abnormalities compared with controls except for the DA concentration at 288 h (1-year-old group); nor were there any differences between the two age groups studied. The data obtained in this investigation clearly indicate age related differences in the striatal dopaminergic neurotransmission after transient cerebral ischemia, in that in the aged brain reactions are markedly delayed after an injurious event such as ischemia. PMID- 1627256 TI - Brain gamma-aminobutyrate aminotransferase (GABA-T) and monoamine oxidase (MAO) in patients with Alzheimer's disease. AB - Activities of Gamma-aminobutyrate aminotransferase (GABA-T) and Monoamine oxidase (MAO)-A and -B were estimated in postmortem brains from 6 control subjects without psychiatric or neurologic disorders and 8 histopathologically verified cases of patients with Alzheimer's disease and senile dementia of Alzheimer type (AD/SDAT). The enzyme activities were examined in four cortical brain regions, three nuclei in the basal ganglia, thalamus and white matter. GABA-T activities in the cortical regions (frontal, parietal, occipital and temporal cortices) and nucleus caudatus were significantly lowered in the AD/SDAT patients. The MAO-A activities were significantly increased in the occipital cortex, caudate nucleus, thalamus and white matter in the AD/SDAT patients. No significant differences were found in the other regions (frontal cortex, parietal cortex, temporal cortex, putamen and globus pallidus). The MAO-B activities in three cortical regions (frontal, parietal and occipital cortices), thalamus and white matter were significantly increased in the AD/SDAT patients, whereas no difference was apparent in the other regions. The changed activities could not be correlated with age or postmortem time. The present results are the first describing decreased GABA-T activities as well as increased MAO-A activities in brain from patients with AD/SDAT, while the results with MAO-B support previous findings. A possible connection was found between the order of magnitude of the changes in enzyme activities and the severity of the disease. PMID- 1627257 TI - Cognitive profile of Alzheimer patients with extrapyramidal signs: a longitudinal study. AB - The cognitive profile of Alzheimer patients without (ADE-, n = 17) and with (AD, E+, n = 15) extrapyramidal signs (rigidity or bradykinesia), at the time of diagnosis, was examined in a 3-year follow-up study and compared to cognitive performance of demented (PD D+, n = 18) and nondemented (PD D-, n = 17) patients with Parkinson's disease and normal elderly controls (n = 19). Although the AD E+ and AD E- groups did not differ significantly at the initial testing, the AD E+ patients showed greater deterioration on visual, praxic and expressive speech functions as well as in category memory. The cognitive profile of the AD E+ patients was similar to that of the PD D+ patients except that the AD E+ patients recognized more false positive targets on list-learning task. The AD E- patients had better preserved praxic functions and WAIS Performance IQ but they, like AD E+ patients, recognized more false positive targets on list-learning than the PD D+ patients did. The results suggest that AD patients with extrapyramidal signs, even if mild, at the time of diagnosis may have greater progression of cognitive impairment, especially on cortical functions, which may explain earlier need for institutional care observed in previous studies as compared to patients without these signs. PMID- 1627258 TI - Monoclonal antibody H3/5-47 recognizes an inducible cell surface antigen expressed differently in endothelium of normal and diseased tissues and in vitro. AB - Monoclonal antibody H3/5-47 was raised against a human melanoma metastasis and recognizes an antigen expressed in the endothelial cells of all normal human organs as assessed by immunohistochemistry. Antigen expression is higher in venous than in capillary or arterial endothelia; capillary endothelia of different microvascular beds, such as skin, lung, gut or liver, may express varying amounts of this antigen. H3/5-47 antigen expression in the endothelia of diseased tissues (inflammatory diseases, neoplasias) largely reflects its expression pattern in normal tissues. As might be anticipated, the highest expression of H3/5-47 antigen is found in resting adult cutaneous and hepatic cavernous venous hemangiomas. In contrast, psoriatic vessels, characterized by hypertrophy and fenestrations, tend to express H3/5-47 antigen at a much lower density. In human umbilical vein endothelial cells, half the single donor cases show no expression of H3/5-47 antigen, while the rest express the antigen at relatively low densities in about half the cells. Treatment with interferon-gamma or thrombin, but not interleukin-1, lipopolysaccharide, endothelial cell growth factor or phorbolester, either enhances or induces de novo expression in cultured human umbilical vein endothelial cells within 24h; maximum expression of H3/5-47 antigen is induced by interferon-gamma within 72 h. H3/5-47 antigen is not similar to other antigens inducible in human umbilical vein endothelial cells such as HLA-DR, ICAM-1, HECA-452, Leu13, MCP-1 or gamma-IP-10. It is not specifically expressed in the endothelium as it may also recognize certain epithelia, peripheral nervous tissue and bone marrow-derived cell populations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627259 TI - Effects of recombinant cytokines on murine megakaryocyte colony formation in a serum-free fibrin clot culture system. AB - A convenient serum-free fibrin clot culture system for murine megakaryocyte progenitor cells was developed. The culture and counting of colonies is much easier in this system, when compared with previously reported serum-free culture methods. Recombinant murine interleukin-3 (rmIL-3) stimulated megakaryocyte colony formation in a dose-dependent manner in this system. While recombinant human granulocyte colony-stimulating factor (rhG-CSF) had no effect on megakaryocytopoiesis, recombinant human erythropoietin (rhEpo) and recombinant human interleukin-6 (rhIL-6) augmented megakaryocyte colony formation stimulated by rmIL-3. The depletion of adherent cells and T cells from the cultured bone marrow did not eliminate the synergistic effect of rhEpo and rhIL-6. PMID- 1627260 TI - Immunohistochemical localisation of transforming growth factor-beta in first and third trimester human placenta. AB - Recently it has been demonstrated that human placental tissue is a source of transforming growth factor-beta (TGF-beta) and that it expresses high TGF-beta mRNA activity. For a better understanding of its in vivo function, it was necessary to determine the site of TGF-beta synthesis in placenta. We have demonstrated that TGF-beta immunoreactivity is present in the cytoplasm of syncytiotrophoblast cells in both early and term placenta. The most intense staining was, however, observed in the first trimester trophoblast syncytial sprouts known to be an early stage in the development of placental villi. These results suggest the involvement of TGF-beta in the paracrine regulation of trophoblast-endometrial interaction. PMID- 1627261 TI - Cellular functions related to metastasis differing between low- and high malignancy variants of AKR lymphoma. AB - Two AKR lymphoma variants of low (LM) and high (HM) malignancy were characterized for cell properties important for metastatic capacity. Previous data suggested that these murine lymphoma variants differed in the late phase of metastasis. In the present study we attempted to determine more accurately the stage in which they differ. The HM cells attached less efficiently than the LM ones to both endothelial cells (5 times) and extracellular matrix (twice), possibly indicating a more efficient extravasation capacity of the HM cells. The level of heparinase was low in the two variant cells. Attachment to liver sections was, however, more efficient with the HM than with the LM cells. PMID- 1627262 TI - Detection of Borrelia burgdorferi in human blood and urine using the polymerase chain reaction. AB - We investigated the use of the polymerase chain reaction (PCR) to detect Borrelia burgdorferi strain B-31 in human blood and urine experimentally inoculated with 5 and 1 borreliae/cm3, respectively, and to biotinylate a DNA probe specific for B. burgdorferi in the dot blot and Southern blot assays. When the blood and urine samples were subjected to PCR, a 370-bp amplified product was consistently visible on agarose gel electrophoresis after 30 and 45 cycles, respectively. The total human genomic DNA extracted from a 1-cm3 sample of inoculated blood was approximately 6.25 micrograms, and the total amount of B. burgdorferi DNA was estimated to be 0.01 pg/6.25 micrograms of the human DNA. For PCR, 2.5 micrograms of human DNA which contained the equivalent of 0.004 pg of borrelia DNA (approximately two borreliae) were used for enzymatic amplification. When 1/20 or 1/10 of the PCR-amplified products were used either for dot blot or Southern blot hybridization, the accessible copies of amplified B. burgdorferi DNA were sufficient for detectable hybridization to occur. PCR amplification of B. burgdorferi DNA in clinical specimens followed by dot blot hybridization may be a valuable adjunct or alternative to current but inadequate laboratory methods for the diagnosis of Lyme disease. PMID- 1627263 TI - Microbial metabolism of quinoline and related compounds. XIII. Purification and properties of 1H-4-oxoquinoline monooxygenase from Pseudomonas putida strain 33/1. AB - 1H-4-Oxoquinoline monooxygenase was purified to homogeneity from Pseudomonas putida strain 33/1 which can use 1H-4-oxoquinoline as sole source of carbon and energy. The apparent M(r) of the native enzyme was determined to be 126,000 by gel chromatography. SDS polyacrylamide gel electrophoresis of the enzyme revealed one protein band corresponding to M(r) 42,000. The enzyme consists of three probably identical subunits with a relative molecular mass of about 42,000. The enzyme requires oxygen and NADH for the reaction and is significantly inhibited by metal ions like Cu2+, Zn2+, Hg2+. The enzyme is specific only for 1H-4 oxoquinoline and the Km values of the enzyme for NADH and 1H-4-oxoquinoline were determined to be 87 microM and 25 microM, respectively. PMID- 1627264 TI - Stimulation of human polymorphonuclear leukocytes by recombinant human interleukin-1 beta. AB - Leukocyte activation is a property of systemic infection. Animal experiments indicate interleukin-1 (IL-1) as a possible modulator, while contradictory results have been reported from in-vitro stimulation of isolated leukocytes. The purpose of the present study was to investigate the activation of isolated polymorphonuclear (PMN) leukocytes in vitro by preparations of recombinant human IL-1 beta and IL-1 receptor antagonist, which in earlier studies could elicit and abrogate, respectively, a sepsis-like syndrome in rabbits. They have also been shown to influence acute phase protein synthesis in mice and rats, and release of leukocyte cathepsin G in vivo. It was found that recombinant human IL-1 beta elicited a dose-dependent luminol-enhanced chemiluminescence response in isolated human PMN leukocytes in the dose range 8.8 x 10(-11)-8.8 x 10(-8) M. The effect could be blocked by prior treatment with the IL-1 receptor antagonist, indicating a direct effect on the specific IL-1 receptor. Preincubation by IL-1 beta enhanced the effect of a secondary challenge with phorbol 12-myristate 13-acetate or formyl-Met-Leu-Phe by 30-40%. The priming effect of rhIL-1 beta could also be blocked by the specific receptor antagonist. In this study, incubation of PMN leukocytes with rhIL-1 beta failed to induce degranulation of both azurophil (neutrophil proteinase 4/proteinase 3) and specific (lactoferrin) granules. rhIL 1 beta has been shown to induce degranulation in vivo, which is thus indicated as an indirect effect. We conclude that IL-1 beta is a direct and specific, but probably weak stimulator of the PMN leukocyte.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627265 TI - Characterization of four genes encoding basic proteins of the porcine spermatid nucleus and close linkage of three of them. AB - Protamines and transition proteins (TNP) play a major role during spermatogenesis and spermatid differentiation. By screening a porcine genomic library with the corresponding cDNAs, we isolated the genomic clones for porcine protamines 1 and 2 as well as for transition proteins 1 and 2. Analysis and comparison of exon intron structure, 5' and 3' untranslated regions and transcription start points revealed features common to their counterparts in other mammals. In contrast to TNP2 the gene for TNP1 is well conserved among species, indicating a non species specific function in the chromatin condensation of the spermatid nucleus. Furthermore, Southern blot hybridization of digested phage DNA demonstrated close linkage between both protamine genes and the gene for transition protein 2 in a 13-kb stretch of DNA. Our observations support the hypothesis that these genes may have evolved by gene duplication. PMID- 1627266 TI - Rat tumor necrosis factor-alpha. Transcription in rat Kupffer cells and in vitro posttranslational processing based on a PCR-derived cDNA. AB - A DNA fragment with a reading frame of 708 basepairs coding for TNF-alpha from rat liver was cloned by the polymerase chain reaction. Using this species specific cDNA a biotin-labelled antisense (-)RNA was transcribed. This probe was used for Northern blot analysis of TNF-alpha gene activation. Exposure of rat Kupffer cells to LPS led to a time-dependent change of TNF-alpha-mRNA expression with a maximum between one and two hours after stimulation. In vitro translation was carried out with sense (+)RNA in the presence of microsomes. SDS gel electrophoresis of the immunoprecipitated proteins revealed the formation of polypeptides with estimated molar masses of 26 and 17 kDa. They correspond to the estimated molar masses of a precursor of TNF-alpha encoded by the entire reading frame and of the mature form of TNF-alpha, respectively. A sequence of the cDNA assumed to code for the leader peptide was deleted and the remainder used for the construction of an expression plasmid. Using this construct, biologically active mature TNF-alpha was expressed in E. coli (10(6) units TNF-alpha per liter of culture medium). The propeptide as well as the biologically active TNF-alpha possess a homology of 92 and 76% to mouse and human TNF-alpha, respectively. PMID- 1627267 TI - Gangliosides in bovine milk. Changes in content and distribution of individual ganglioside levels during lactation. AB - Bovine milk undergoes changes in its ganglioside contents during the different stages of lactation. These contents are higher in colostrum (7.5 mg of lipid bound NeuAc/kg) than in transitional (2.3 mg) or mature (1.4 mg) milk. The sialic acid content of milk follows a similar profile to that of gangliosides with the highest content during the first few days post partum followed by a gradual decrease towards the end of the period studied. When the individual distribution of gangliosides was examined throughout the course of lactation, several changes were also found. GD3 is the major ganglioside (about 60-70%) found; its content decreases from the first to the fifth day, increasing towards the end of the period considered. GM3, GD3 and GT3, sialyllactosylceramide-containing gangliosides account for 80-90% of the total lipid-bound NeuAc content. The most striking change in the ganglioside pattern was the gradual increase in G3. PMID- 1627268 TI - Distinct distributions of D-erythro-neopterin in arteries and veins and its recovery by an enterohepatic circulation. AB - Large amounts of D-erythro-neopterin, a pteridine derivative, are formed from guanosine triphosphate (GTP) by human macrophages upon stimulation with interferon-gamma. In addition, in humans a basal neopterin level in all body fluids is evident also in absence of immunological stimuli. Extremely high concentrations of D-erythro-neopterin were detected in biliary fluid. We therefore investigated, if an enterohepatic circulation might exist for this substance. We quantified concentrations of pteridines in serum obtained from various vessels and in biliary fluid. Samples were collected during surgery of five patients with duodenal ulcer or adenocarcinoma of the stomach. Our data clearly demonstrate the existence of an enterohepatic circulation for the recovery of neopterin which seems to be specific for this substance. The relative distributions of neopterin concentrations in the gastrointestinal tract and vessels were seen invariably in all patients and were consistent with findings in five corpses examined post mortem. In addition, significantly higher neopterin concentrations, were found in arteries than in veins. The data indicate that neopterin derivatives are consumed in the peripheral capillary system and an enterohepatic circulation is established to maintain constant blood levels of neopterin derivatives. Furthermore, we suppose that the liver is the source of constitutive neopterin concentrations. PMID- 1627269 TI - Peer review. PMID- 1627270 TI - Activity of liposomal interleukin-2 in vitro. AB - Preclinical in vitro assessment of highly purified natural human interleukin-2 (IL-2) packed in egg lecithin liposomes was performed in short- and long-term T cell cloning and propagation systems, and in experiments testing induction of lymphokine-activated killer (LAK) cells. Liposomal IL-2 (lip-IL-2) was essentially as active as free natural or recombinant IL-2 for cloning and culture of both helper and cytotoxic alloreactive T cells. However, lip-IL-2 was found to be markedly inferior to free natural or recombinant IL-2 for the induction of LAK cells from normal donors. Nevertheless, lip-IL-2 was able to maintain LAK cytotoxicity of populations preactivated with free IL-2. These results suggest that lip-IL-2 can interact with activated T cells and LAK cells in the same way as free IL-2, but that it is much less efficient at activating LAK-cell precursors. PMID- 1627271 TI - Antitumor activity of recombinant human tumor necrosis factor in combination with hyperthermia against heterotransplanted human prostatic carcinoma and its lymph node metastasis in nude mice. AB - The antitumor activity of recombinant human tumor necrosis factor (rhTNF) against heterotransplanted human prostatic carcinoma (PC-3) and spontaneous lymphatic tumor metastasis was studied in vivo. The spontaneous lymphatic metastasis of PC 3 tumor was found in approximately 50% of cases. Significant antitumor activity was observed with repeated intratumoral administration of a large dose of rhTNF, not only on the subcutaneous tumor xenografts but also on the lymph node metastases. Strong antitumor activity could be achieved even with the intratumoral administration of a small dose of rhTNF in combination with mild hyperthermia on either the transplanted tumors or on the metastatic tumors. PMID- 1627272 TI - Combination biotherapy utilizing interleukin-2 and alpha interferon in patients with advanced cancer: a National Biotherapy Study Group Trial. AB - The National Biotherapy Study Group (NBSG) conducted a broad phase II trial using interleukin-2 (IL-2) by continuous infusion and alpha interferon (IFN) subcutaneously in 267 patients with a variety of advanced cancers, including 29 with breast cancer, 89 with renal cancer, and 69 with melanoma. IL-2 [18 million international units (MIU)/m2] was given by continuous infusion for 108 hours with 3 mu/m2 subcutaneous IFN every other day during the IL-2 infusion. The patients were treated for 1 week followed by a 2-week rest. After two cycles of treatment, patients were evaluated for response. Of the 237 patients evaluable for response, 20 (8%) had a complete or partial response and 128 (54%) were stable. Therefore, 62% of the evaluable patients were nonprogressive during the first 90 days of IL 2/IFN therapy. The objective response rate was 11% in melanoma, 7% in renal cancer, 14% in breast cancer, and 3% in patients with a variety of malignancies for an overall response rate of 7% in these patients with advanced cancer. The patients were treated on a general medical ward and tolerated treatment well with fatigue and fever being nearly universal. Dyspnea, pruritus, chills, and elevated creatinines were frequent but less common. This combination biotherapy regimen has minimal activity in a variety of advanced cancers and must be compared with the best existing chemotherapy for each cancer type in randomized, prospective trials. PMID- 1627273 TI - Mimicking of superoxide dismutase activity by protein-bound polysaccharide of Coriolus versicolor QUEL, and oxidative stress relief for cancer patients. AB - The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) has been found to express antioxidant activity as an "ion-radical scavenger" in diamine oxidation reactions. The mode of this expression was examined to determine whether the drug functioned as a simple radical scavenger or mimicked the action of superoxide dismutase (SOD). The latter was confirmed in both enzymatic and nonenzymatic superoxide anion radical (O2-.) producing systems in vitro. The SOD mimetic activity of PS-K was demonstrated by quantitative analysis of hydrogen peroxide as the end product of O2-., its formation being assisted catalytically by SOD or PS-K. Analysis by electron spin resonance also confirmed the SOD mimetic activity of PS-K in a xanthine-xanthine oxidase reaction. Relative SOD activity with PS-K was approximately 1/8,000 in a KO2-O2-.-producing system. The SOD mimetic activity of PS-K resisted treatment by 0.7N HCl, 0.7N NaOH, boiling for 30 minutes in a double water bath, and digestion by pronase. Fractionation according to differences in molecular mass caused no significant increase in relative SOD activity within a certain range of molecular mass, indicating that there is no definite molecule expressing SOD mimetic activity. Tumor-bearing rats and human patients with digestive tract cancer who suffered from oxidative stress were relieved by a single intraperitoneal administration of PS-K or a 1-day peroral prescription. PMID- 1627274 TI - Enhanced cell-mediated cytotoxicity by interferon-gamma and interleukin-2 against syngeneic murine mammary adenocarcinoma. AB - The effect of murine recombinant interferon-gamma (IFN-gamma) on cell-mediated cytotoxicity against tumor cells in vitro and in vivo was investigated using a spontaneously developed, weakly immunogenic, syngeneic murine mammary adenocarcinoma, designated JC, as the target. Preincubation of JC tumor cells with IFN-gamma increased the susceptibility of lysis by both cytotoxic T lymphocytes and interleukin-2 (IL-2)-induced lymphokine-activated killer cells in an IFN-gamma dose-dependent manner. A direct injection of IFN-gamma (10,0000 U/d) daily for 5 consecutive days into the JC tumor nodule on the backs of BALB/c mice reduced the tumor growth in comparison with that of the control group. This antitumor activity was further enhanced by combination with a simultaneous intraperitoneal injection of IL-2 (300,000 IU/d) daily for 5 consecutive days. Phenotypic examination of tumor-infiltrating lymphocytes after injection of IFN gamma plus IL-1 revealed an increased percentage of the cells expressing asialo GM1, L3T4, and IL-2 receptors. Additionally, an enhanced expression of major histocompatibility complex class I molecules on the JC tumor cells was detected. These results indicated that a direct injection of IFN-gamma into the tumor accompanied with the administration of IL-2, by enhancing cell-mediated immunity of the hosts and expression of major histocompatibility complex class I antigens on target cells, will be of potential clinical value. PMID- 1627275 TI - Structure of N,N-[bis(2-pyridylmethyl)-gamma-aminobutyrato]copper(II) bromide methanol solvate. AB - [Cu(C16H18N3O2)]Br.CH4O, Mr = 459.83, orthorhombic, P2(1)2(1)2(1), a = 10.452 (4), b = 12.197 (7), c = 14.984 (6) A, V = 1910 (3) A3, Z = 4, Dm = 1.61 (1), Dx = 1.599 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 32.37 cm-1, F(000) = 932, T = 174 K, R = 0.0396, wR = 0.0419, 1146 observed reflections [I greater than 3 sigma(I)]. The title compound is a polymeric species in the solid state, with a unit cell consisting of two segments of one-dimensional chains. The ligand, a derivative of gamma-aminobutyric acid in which the amino group is substituted with two 2-pyridylmethyl moieties, coordinates to one copper atom through the three nitrogen atoms and to another copper atom through the two carboxylate oxygen atoms. The copper(II) atom has a pseudo square-pyramidal geometry, distorted by a distant sixth interaction to a carboxylate oxygen atom [Cu-O(2), 2.770 (7) A]. PMID- 1627276 TI - Structure of the anti-malarial drug primaquine diphosphate. AB - 8-(4-Amino-1-methylbutylamino)-6-methoxyquinoline bis(dihydrogenphosphate), C15H23N3O2+.2(H2PO4)-, Mr = 455.35, triclinic, P1, Z = 2, a = 7.389 (6), b = 8.862 (4), c = 16.055 (10) A, alpha = 97.57 (2), beta = 100.21 (3), gamma = 77.01 (2) degrees, V = 1003.6 (5) A3, Dm = 1.495 (by flotation), Dx = 1.507 g cm-3, lambda (Cu K alpha) = 1.5418 A, mu(Cu K alpha) = 24.48 cm-1, F(000) = 480, room temperature, R = 0.068 for 3448 observed reflections. The above working cell is related to the reduced cell with angles alpha = 82.43, beta = 79.79 and gamma = 77.01 degrees by the transformation (-100/0 -10/001). Primaquine diphosphate was crystallized in the dicationic form with protonation on the quinoline ring nitrogen atom and on the terminal amino group. One dihydrogenphosphate anion is chelated by the quinoline ring and the butylamino side chain. The other dihydrogenphosphate anion is hydrogen bonded to the terminal amino group. The C(14) atom is nearly in the plane of the quinoline ring with a C(9)-C(8)-N(13) C(14) torsion angle of 169 degrees. The butyl-diamino side chain is kinked by rotation about the C(14)-C(16) bond with a N(13)-C(14)-C(16)-C(17) torsion angle of -59 degrees. The C(15) methyl substituent is in line with the rest of the butyl chain. The terminal amino group N(19) is hydrogen bonded to three symmetry related phosphate groups while N(1) and N(13) are 'chelated' to a fourth phosphate group. PMID- 1627277 TI - Reflections on joining the circus of life. PMID- 1627278 TI - The family's role in stroke rehabilitation. A review of the literature. AB - Clinical and research attention in stroke care has been on managing the acute stage of stroke recovery and on evaluating the effectiveness of relatively short term rehabilitation programs. However, studies suggest that stroke can diminish quality of life and the well-being of patients' families. This article reviews the literature pertaining to the effects of stroke on family functioning and discusses stroke in terms of clinical problems that make rehabilitation a family dilemma. Issues identified in the literature include the need for family assessment, education, advocacy and counseling to foster treatment compliance and social support after stroke. PMID- 1627279 TI - Beaumont Lifestyle Inventory of Social Support. Can it predict disposition prior to an inpatient rehabilitation admission? AB - Predicting which rehabilitation patients will ultimately be discharged to a nursing home is a difficult task because methods used to evaluate preexisting home environment and quantify social support have been inadequate. To address this problem, the Beaumont Lifestyle Inventory of Social Support (BLISS) was developed. This questionnaire examines the family's willingness to care for, supervise and provide financial assistance to the patient. Organized into 10 weighted questions, BLISS results in a maximum score of 12. A prospective study was conducted to determine the correlation of the BLISS score with discharge disposition. Prior to rehabilitation admission, continuing care coordinators administered the BLISS to an involved family member of each patient. After 6 months, all BLISS forms were scored and compared with discharge disposition. Seventy-nine patients were included in this study and six (7.6%) were discharged to nursing homes. Comparison of BLISS scores obtained in patients discharged home versus nursing home revealed averages of 9.3 and 4.0, respectively (P less than 0.0006). These findings indicate that BLISS can quantify a patient's social situation and provide a predetermination of the social factors that lead to nursing home discharge. Consequently, BLISS will be a useful screening tool during the rehabilitation selection process. PMID- 1627280 TI - Neuroendocrine changes during functional electrical stimulation. AB - This study examined the effects of a computerized functional electrical stimulation exercise program on plasma beta-endorphin-like immunoreactivity (BEP ir), cortisol levels and depression parameters in spinal cord-injured individuals. Nine subjects from 1.2 to 33.5 yr postinjury with both motor and sensory complete lesions between C5 and T12 participated. It was determined that patients who sustained spinal cord-injuries less than 5 yr before this study had lower than normal baseline levels of BEP-ir and flattened circadian rhythms. Patients who sustained their injury greater than 5 yr before this study had higher baseline levels of BEP-ir with some return to normal circadian rhythmicity. Baseline cortisol levels, regardless of time since injury, appeared to be dysregulated. Regular exercise with computerized functional electrical stimulation caused significantly (P less than 0.05) sustained increases in BEP-ir in all patients and improved the regulation of cortisol. Furthermore, the more strenuous the exercise training, greater increases in BEP-ir levels were seen. Last, depression scores improved, which suggests a possible association between subjective mood and BEP-ir levels. PMID- 1627281 TI - The effect of different needle recording electrodes on somatosensory-evoked potentials and intertrial waveform variation. AB - This investigation examined the cortical somatosensory-evoked potentials (SEP) waveforms obtained from four sets of commercially available subdermal needle electrodes in 19 normal subjects. The composite materials of the four electrodes were stainless steel and a platinum/iridium alloy. Tibial nerve SEP peak latencies for P37 and N45 as well as P37/N45 amplitudes were recorded from each electrode pair in a random fashion. Using nonparametric analysis, no significant differences of waveform parameters were found between electrode pairs (P greater than 0.01). Correlation evaluation demonstrated values in excess of 0.92. Additionally, intertrial waveform analysis for each of the electrode pairs was performed. Again, nonparametric evaluation demonstrated no statistically significant waveform differences. Correlation coefficients were also highly correlative. Variable temperature response to prolonged tibial nerve stimulation was recorded that did not significantly effect the latencies or amplitudes of the cortical SEP responses. We conclude that within temperature ranges typically encountered in clinical practice, there is no statistically significant waveform differences recorded with commonly available subdermal needle electrodes. Additionally, although intertrial waveform variation may exist during SEP recordings, these differences do not reach statistically significant levels. PMID- 1627282 TI - Contralateral v ipsilateral cane use. Effects on muscles crossing the knee joint. AB - Although using a cane contralaterally has been shown to reduce muscular activity across the hip joint, little is known about effects on the knee. We measured muscular activity around the knee in 10 able-bodied subjects. We simultaneously recorded integrated rectified surface electromyographic activity from the right quadriceps, medial and lateral hamstrings, gastrocnemius and hip abductors during various standing maneuvers: two-legged stance, unsupported one-legged stance and one-legged stance putting maximal, moderate (20% body weight) or minimal (10% body weight) force through an ipsilateral or contralateral cane. Electromyographic activity was expressed as the percentage of that recorded during unsupported one-legged stance in each muscle. Hip abductor activity was lowest when maximal weight was placed through a contralateral cane (66%) and highest with maximal weight ipsilaterally (424%). Medial hamstrings activity increased by 404% and 200%, respectively, when maximal and moderate force was applied to a contralateral cane, although there was no change with ipsilateral cane. Lateral hamstrings were also most active during contralateral cane use. Quadriceps activity decreased using a cane in either hand with moderate or minimal force (range 57 to 84%). Gastrocnemius activity decreased during contralateral (60 to 66%) and ipsilateral (75 to 96%) cane use. This data suggests that forces generated by muscular activity around the knee are not uniformly diminished by holding a cane in the contralateral hand and may even be increased. PMID- 1627283 TI - Driving evaluation after traumatic brain injury. AB - Traumatic closed head injury results in a variety of cognitive and behavioral deficits that may be difficult to assess fully. Adequately evaluating driving safety is a common and important problem for health care professionals. The purpose of this study was to examine the relationship between standardized measures of cognitive function and measures of driving performance in patients with closed head injuries and in their age-matched relative or friend cohorts. Thirteen patients were evaluated. They had each sustained a closed head injury (followed by more than 1 h of coma) 3 to 6 months before testing. Their scores were analyzed along with those of seven cohorts. Assessments of cognitive function and behind-the-wheel driving performance were conducted by examiners blinded to subjects' group membership and medical condition. There was a significant relationship (r = 0.44) between the sum of rated scores of the Tactual Performance Test and Trail Making Test and the global pass/fail ratings of the behind-the-wheel driving test, but it was not related to the driving performance score. The difference between the verbal and performance IQs, and the difference between the block design and other performance tests of the Wechsler Adult Intelligence Scale-Revised were also not significantly related to driving performance. These results suggest that tests of cognitive function alone are not adequate to predict driving performance, and should be used along with standardized driving performance evaluations before recommendations are made. PMID- 1627284 TI - Rheumatology rehabilitation: the role of a physical medicine and rehabilitation liaison consultation service. A commentary. PMID- 1627285 TI - Chin augmentation. An important adjunctive procedure to rhinoplasty. AB - Augmentation mentoplasty is a cosmetic procedure designed specifically to supplement deficient fullness of the mental area. Patients seeking care from rhinoplastic surgeons for nasal corrective procedures may not be aware of a deficiency, which is the most common abnormality in this area. Complete evaluation of the full facial profile, which should be performed in all potential rhinoplasty patients, identifies such abnormalities. The general concepts of preoperative evaluation, corrective options available, including make of implant materials, and complications are discussed. Patients with mild to moderate microgenia can be simply corrected by augmentation mentoplasty to balance the facial profile. The most common method of adding fullness in the chin area is use of an implantable material. This article discusses the advantages and disadvantages of the available materials. PMID- 1627286 TI - Perilymph fistulas. Clinical criteria. AB - A perilymph fistula may be defined as an abnormal opening between the inner ear and the external surface of the labyrinth capsule, which allows the escape of perilymph and causes specific disorders of hearing, balance, or both. Its diagnosis remains somewhat controversial. This communication presents a defined set of clinical diagnostic criteria, the historic context by which those criteria have been developed, the histopathologic and clinical studies by which they have been challenged or substantiated, and the deficiencies that remain in our understanding of the pathogenic mechanisms that allow for abnormal cochlear or vestibular function. PMID- 1627287 TI - Perilymph fistula. PMID- 1627288 TI - Revision rhinoplasty. An analysis of aesthetic deformities. AB - Revision rhinoplasty can present difficult and challenging problems, which maximally test the skill and judgment of the facial plastic surgeon. We conducted a retrospective study of 1221 consecutive rhinoplasties, of which 170 were revision procedures. The rate of revision of our own procedures is 5.3%. Postrhinoplastic deformities are divided anatomically into the upper, middle, and lower thirds of the nose. The largest category of deformities occur in the lower thirds of the nose, in which bossa are the most common problem. Overall, pollybeak is the most common deformity in 33% of the procedures performed, followed by bossa in 26%, and excessive dorsal removal in 24%. We analyzed the causes and selected management of these cases. PMID- 1627289 TI - The superior trapezius myocutaneous flap in head and neck reconstruction. AB - The superior trapezius myocutaneous flap, based on the paraspinous perforating branches of the intercostal vessels, is generally not a first-line choice for reconstruction of head and neck defects. However, after wound breakdown following radical neck dissection and radiation therapy, the superior trapezius flap is extremely reliable for coverage of exposed major neck vessels. The flap was used in 30 patients undergoing lateral neck reconstruction. All 30 patients had undergone prior neck dissection and all but two had undergone prior radiation therapy. There were no flap failures. The superior trapezius flap is unique among other regional myocutaneous flaps presently in use in that it has a superiorly based pedicle, which reduces the problem of gravitational pull on the suture lines of severely unfavorable recipient beds. Another advantage of using the denervated muscle of this flap is that it imposes no additional functional loss. The deficiencies of this flap are primarily related to its limited arc of rotation, thereby precluding its use when resurfacing defects that extend beyond the midline of the neck. The reliability of the superior trapezius flap after neck dissection can be explained by the angiosome concept. Based on that concept, previous ligation of the transverse cervical vessels during a neck dissection serves to simultaneously stage this flap, thereby improving its reliability and potential surface area available. PMID- 1627290 TI - The pectoralis major myofascial flap for intraoral and pharyngeal reconstruction. AB - The pectoralis myocutaneous flap has been widely used for reconstruction of oral cavity and pharyngeal defects. However, it has several disadvantages, such as chest distortion, hair growth at the reconstructed site, and excessive bulk, all of which can be avoided by the use of the pectoralis myofascial flap. Oral cavities and pharyngeal defects, ranging in size from 4 to 9 cm in largest' dimension, in 26 patients were reconstructed with the pectoralis myofascial flap. All but three defects were successfully reconstructed. The surface of the flap was covered by squamous epithelium in 1 month. The flap remained healthy during and after radiotherapy. The pectoralis myofascial flap is ideal for soft-tissue coverage of small- to medium-size oral cavity and pharyngeal defects. Its major advantages over the pectoralis myocutaneous flap are decreased bulk and improved cosmesis. PMID- 1627291 TI - Fluorescein and acidosis. Implications for flap perfusion studies. AB - The visual fluorescein technique underpredicts survival of a skin flap during the first 24 hours after raising the flap. This problem limits its use as a research and clinical tool. There is no compelling explanation for this observation, but two facts are known: fluorescein is a derivative of phthalein, a pH indicator, and ischemic tissues become acidotic, with the pH falling below 7.0. These observations lead to the hypothesis that acidosis quenches fluorescence in distal skin flaps. No data could be found regarding this effect. Therefore, the effect of acidosis on sodium fluorescein was studied in vitro. A spectrophotometer was used to measure the intensity of the fluorescence of sodium fluorescein in buffered solutions of different hydrogen ion concentrations. Two studies were performed at different concentrations of fluorescein. At a concentration of 10( 5) g/mL, there is a drop of 26% in fluorescence intensity from pH 7.5 to 7.0, and 51% between pH 7.5 and 6.5. At 10(-7) g/mL, there is a 43% decrease in fluorescence between pH 7.5 and 6.5. This study supports our hypothesis that acidosis quenches the fluorescence of fluorescein. This effect must be considered when interpretating basic studies of skin flap microcirculation. PMID- 1627292 TI - Clinical determinants for the management of thyroid nodules by fine-needle aspiration cytology. AB - To evaluate the utility of clinical features for the selection of patients with thyroid lesions suitable for diagnosis by fine-needle aspiration cytologic study, we reviewed 149 cases with complete clinical histories, laboratory evaluations, fine-needle aspirates, and histologic study of the index lesion. Review of these data demonstrated that only the presence of lymphadenopathy was of statistical value in the distinction of benign from malignant nodules. Moreover, once an aspiration diagnosis of "follicular neoplasm" had been made, no clinical, radiologic, or laboratory test aided in the distinction of follicular adenoma from follicular carcinoma. PMID- 1627293 TI - Effect of extraluminal oxygen on carbon dioxide laser ignition of endotracheal tubes. AB - Ignition times of endotracheal tubes used in laser surgery have been determined in room air with oxygen flowing through the tube. Using uncuffed endotracheal tubes in children, we measured the oxygen level around the endotracheal tube at the vocal cords and found that it closely approximates the inspired oxygen concentration. We then tested Rusch red rubber and polyvinyl chloride endotracheal tubes while varying the external oxygen concentration. Little difference in ignition time was found for the polyvinyl chloride tube. The red rubber tube ignited significantly faster as the ambient oxygen levels were increased to as little as 30%. Our tests indicate that uncuffed red rubber tubes are not safer than polyvinyl chloride tubes when used with the carbon dioxide laser. All endotracheal tubes used with the laser should be tested for ignition at various extraluminal oxygen concentrations. PMID- 1627294 TI - Is nasotracheal intubation safe in surgery for mandibular cancer? AB - A retrospective study of problems of postoperative airway maintenance after surgery for mandibular cancers was conducted. Twenty-seven patients treated in an intensive care unit after mandibular resection and primary reconstruction were included. The mean duration of nasotracheal intubation in 22 patients was 33.7 hours. Reintubation because of breathing difficulties was required in four cases. In one of these cases, failed intubation led to an emergency cricothyroidostomy. Failure to perform reintubation resulted in the death of one patient. One patient was tracheostomized after 5 days of nasotracheal intubation. Prolonged nasotracheal intubation after major surgery for oral malignant neoplasms may be an alternative to tracheostomy, provided that adequate monitoring is available after extubation. The safe duration of endotracheal intubation is difficult to determine. Primary reconstruction does not eliminate the need for an artificial airway after tumor surgery. PMID- 1627295 TI - Human olfactory biopsy. The influence of age and receptor distribution. AB - Thirty-six mucosal specimens were obtained with a biopsy instrument from the upper nasal septum of 12 human autopsy cases before the en bloc removal of the entire olfactory area. Examination of these 36 specimens with transmission electron microscopy demonstrated olfactory epithelium in only 17. A significant negative correlation (r = -.728) was noted between the age of the subject and the probability of obtaining olfactory epithelium, supporting the idea that the olfactory mucosa is gradually replaced by respiratory epithelium with aging. Using the en bloc specimens, the distribution of olfactory epithelium was reconstructed from light microscopic examination of silver-stained sections. Multiple patches of respiratory epithelium were observed over the upper portion of the nasal septum and superior turbinates, ie, the presumptive olfactory area. On transmission electron microscopic examination, frequent respiratory metaplasia was also suggested. Within the area of respiratory metaplasia, supporting cell like and microvillar cell-like structures often were found; these structures may be remnants of olfactory epithelium. The sampling of olfactory tissue with a biopsy procedure is hampered by the irregular and patchy distribution of olfactory epithelium. The invasion of respiratory epithelial patches into the olfactory mucosa seems to be characteristic of the human olfactory epithelium and may increase as a function of age. Thus, conclusions about the structure of the olfactory mucosa in an individual patient must be based on several tissue samples. PMID- 1627296 TI - Polysomnographic and clinical findings in children with obstructive sleep apnea. AB - A retrospective study was conducted to determine which types of children might have polysomnographic findings that are most compatible with obstructive sleep apnea (OSA). The charts of 93 patients who were aged 18 months to 12 years were examined. All 93 patients had symptoms that were initially suggestive of OSA, and they underwent polysomnography. The types of presenting symptoms and associated illnesses were noted. Physical findings, including height, weight, and tonsil size, were examined. Of 93 patients with symptoms that were suggestive of OSA, 34 met sleep study criteria for OSA. In 44 patients, OSA was not demonstrated, and 15 patients had other results. On the basis of age, sex, and symptoms, no significant differences could be found between the group with OSA and the group with normal polysomnographic findings. Cor pulmonale, tonsil hypertrophy, and failure to thrive were associated with OSA. Surprisingly, obesity was not significantly associated with OSA. PMID- 1627297 TI - Demonstration of interleukin 6 in middle ear effusions. AB - In response to infection in the middle ear, inflammatory cells produce cytokines- potent regulators and mediators of the immune response. In an earlier study, we demonstrated that levels of the cytokine interleukin 1 were higher in middle-ear effusions from younger children, while levels of the cytokine tumor necrosis factor were higher in middle-ear effusions from older children and in those requiring tympanostomy on multiple occasions. In this study, we evaluated middle ear effusions for levels of the cytokine interleukin 6. Activities of interleukin 6 include stimulation of bone erosion and production of antibodies and fever. Using an enzyme-linked immunosorbent assay system, significant levels of interleukin 6 (greater than 0.2 pg/mL) were found in 14 (36%) of 39 middle-ear effusions from 25 children with otitis media with effusion. The mean (+/- SE) level of interleukin 6 in middle-ear effusions was 173.9 +/- 74.7 pg/mg of total protein. Like interleukin 1, levels of interleukin 6 were higher in younger children. Tumor necrosis factor may be an important regulator of the local immune response in the middle-ear cleft during persistence of otitis media with effusion, while interleukin 1 and interleukin 6 may be important regulators during the early stages of otitis media with effusion. PMID- 1627298 TI - Inhibition of lymphoproliferation by middle ear effusion in experimental otitis media. AB - In this study, experimental otitis media was created in the chinchilla by direct middle ear challenge with Escherichia coli endotoxin, Streptococcus pneumoniae, Haemophilus influenzae, or Pseudomonas aeruginosa. The effusions recovered from the chinchillas in all four challenge groups were shown to inhibit the lymphoproliferative response of chinchilla peripheral blood lymphocytes to stimulation with phytohemagglutinin. The effect was dose dependent, and for effusions of infectious origin, the degree of inhibition was directly related to the duration of infection. Presence of the inhibitor in plasma was undocumented, suggesting a local production within the middle ear. Lymphocytes from middle ears infected with bacteria but not middle ears challenged with endotoxin were hyporesponsive or nonresponsive to stimulation with phytohemagglutinin. These results confirm the presence of an inhibitor of the lymphoproliferative response in experimental otitis media of different etiologies. PMID- 1627299 TI - Luetic cervical adenitis in patients with human immunodeficiency virus type 1 infection. AB - The clinical course of syphilis may be altered in some patients with human immunodeficiency virus type 1 infection. We report two cases of syphilis in patients with human immunodeficiency virus type 1 infection who presented with marked unilateral anterior cervical adenopathy after engaging in oral-genital sex. Neither of the patients had evidence of oropharyngeal chancres. One patient developed a cutaneous rash of secondary syphilis soon after the cervical adenopathy developed. Both patients responded well to antibiotic therapy. PMID- 1627300 TI - Curettage of nontuberculous mycobacterial cervical lymphadenitis. AB - Cervicofacial nontuberculous mycobacterial infections of the head and neck are difficult to treat surgically because of their common location near the branches of the facial nerve. Curettage of these lesions through a small skin incision makes treatment simple without injury to the facial nerve fibers and leaves the patient with an excellent cosmetic result. Most discussions on the topic, however, favor complete surgical excision even though curettage has been reported as a safe and excellent means of treatment. For the past 2 years, the department of otolaryngology-head and neck surgery at the Geisinger Medical Center, Danville, Pa, has used curettage in seven patients as the primary treatment modality for these facial and cervical infections. A review of these cases is presented. PMID- 1627301 TI - Allergy is not a significant cause of nasal polyps. PMID- 1627302 TI - Casual surgical techniques in January 1992 photograph. PMID- 1627303 TI - Pathologic quiz case 2. Plexiform neurofibroma. PMID- 1627304 TI - Pathologic quiz case 1. Cervical thymic cyst. PMID- 1627306 TI - Is high technology medicine a threat to health care? PMID- 1627307 TI - Prevention and treatment of osteoporosis: summary of the statement prepared by the consensus development conference of the Finnish Academy of Science and the Finnish Medical Society Duodecim. PMID- 1627305 TI - Beta-carotene, vitamin A and prostatic cancer. PMID- 1627308 TI - Peroxisomal diseases. AB - The peroxisomal diseases, which are rare inborn metabolic errors, often have serious effects on the well being of the individual and many of them are fatal at an early age. The Zellweger cerebro-hepato-renal syndrome represents a group consisting of diseases with a generalized loss of peroxisomal functions and is considered as a prototype for peroxisomal dysfunction. The largest group includes those diseases where only a single peroxisomal function is impaired. The most common peroxisomal disease, x-linked adrenoleukodystrophy (ADL), belongs to this group, and neurological symptoms dominate among the patients. The primary diagnosis is usually based on clinical findings and measurement of accumulated or depleted metabolites in the body (e.g. very long chain fatty acids, bile acid intermediates or plasmalogens). Some progress has been made in treating of the peroxisomal diseases. Many patients with x-linked ALD have benefitted from the supplementation of the diet with long chain monounsaturated fatty acids like erucic acid or oleic acid with the simultaneous restriction of very long chain fatty acids. Docosahexenoate (C22:1) has also shown promising results in some studies. PMID- 1627309 TI - Interventional uroradiology today. PMID- 1627311 TI - Polymerase chain reaction (PCR)--a new tool in clinical medicine. PMID- 1627310 TI - Advances and retreats in the molecular genetics of major mental illness. AB - With the last two decades, the importance of genetic factors in the aetiology of major mental illness has been firmly re-established and psychiatric research has now firmly embraced the era of molecular genetics. Despite a number of false starts in the study of schizophrenia and affective disorder, there have been successes in unmasking some of the aetiological secrets of Alzheimer's disease. We will give an overview of the rationale behind these studies and the major findings to date. PMID- 1627312 TI - From one to millions--the polymerase chain reaction in diagnosis. PMID- 1627313 TI - PCR-based mutation analysis in cystic fibrosis. PMID- 1627314 TI - PCR in the diagnosis of phenylketonuria. PMID- 1627315 TI - Applications of PCR in the diseases of genetic isolates. PMID- 1627316 TI - The use of PCR in diagnosing lipoprotein disorders. PMID- 1627317 TI - PCR in the analysis of mutations in mitochondrial DNA. PMID- 1627318 TI - PCR in the diagnosis of viral hepatitis. PMID- 1627319 TI - When government regulations go too far. PMID- 1627320 TI - The total greenhouse warming potential of technical systems: analysis for decision making. AB - Mitigation of greenhouse gas (GHG) warming of the atmosphere concerns many industrial and government sectors. Since no quantitative measures existed to compare the complete effects of processes and their GHG emissions, past decisions were based primarily on qualitative or partial analyses. Three developments extending existing methods are proposed. First, a systems perspective should be used to facilitate identification of all GHGs associated with industrial or agricultural operations and reduce chances of unanticipated side effects following any decision. Second, the entire life-cycle plus aftereffects should be used to portray system time effects. Third, a Warming Forcing Factor and Index are suggested for use to completely describe the effect of each GHG emitted by a system and relate it to useful output, as well as to composite the effects of all emissions. As an illustration of its suitability for individual technology assessments, results are presented for a biomass-to-methanol vehicle fuel system. PMID- 1627321 TI - Flow rates and compositions of incinerated waste streams in the United States. AB - The quantity and composition of RCRA hazardous wastes incinerated during 1986 were examined using the National Hazardous Waste Survey. This Survey, collected for U.S. EPA by the Research Triangle Institute, is the most extensive examination of hazardous waste generation and management available. The survey data show that although a wide variety of hazardous wastes were treated by incineration, more than 75 percent of incinerated waste streams were from chemical manufacturing. The survey data also show that more than 90 percent of the incinerated wastes were treated by incinerators located at the facility generating the waste. Despite the predominance of a single industrial sector in generating incinerated hazardous wastes, the compositional profile of the wastes is far from uniform. To illustrate this variability, the metals and chlorine content of the wastes are reported along with the sources of the metal and chlorine loadings. PMID- 1627322 TI - Synthesis of environmental evidence: nitrogen dioxide epidemiology studies. AB - The use of meta-analysis is becoming more common in the medical literature, but it is not common in the environmental literature. Although meta-analysis cannot combine a group of poorly executed, conflicting studies to get an unequivocal answer, there are certain situations where it can be helpful. The inability of studies to produce similar results may be a function of the power of the studies rather than a reflection of their quality. The literature on the effects of nitrogen dioxide on the odds of respiratory illness in children is such an example. Three quantitative methods for the synthesis of this evidence are presented. Although the methods produce slightly different results, the conclusion from all three methods is that the increase in the odds of respiratory illness in children exposed to a long-term increase of 30 micrograms/m3 (comparable to the increase resulting from exposure to a gas stove) is about 20 percent. This estimated increase is not sensitive to the method of analysis. PMID- 1627323 TI - Atmospheric concentrations of PCDDs/PCDFs in southern California. AB - A comprehensive air toxics measurements program designed to establish baseline concentrations of atmospheric polychlorinated dioxins and dibenzofurans (PCDDs/PCDFs) in the South Coast Air Basin has been completed. The program utilized state-of-the-art air sampling and laboratory analysis techniques (HRGC/HRMS) to quantify the fifteen 2,3,7,8-substituted PCDDs/PCDFs congeners of primary toxicological significance. This study, which included nine discrete sampling sessions between December 1987 and March 1989, provides the first systematic assessment of ambient PCDDs/PCDFs concentrations in the state of California. The highest PCDDs/PCDFs concentrations noted during this study occurred in December 1987. This period was dominated by off-shore air flows, suggesting a regional air mass and transport phenomena. Concentrations of the PCDDs/PCDFs were diminished markedly in subsequent sampling sessions where air flow patterns were primarily of on-shore or of coastal origin. Ambient PCDDs/PCDFs concentrations, expressed as toxic equivalents, were highest during the December 1987 sampling period. The El Toro monitoring site, located approximately 40 miles southeast of Los Angeles, consistently showed the lowest measured ambient PCDDs/PCDFs concentrations and toxic equivalents values. In the majority of the sessions and samples examined the PCDDs/PCDFs congener profiles strongly suggest combustion source influences. Typical of combustion source profiles, 1,2,3,4,6,7,8-HpCDD was the predominant 2,3,7,8-substituted species and most prevalent PCDD after OCDD. The congener of highest toxicological significance, 2,3,7,8-TCDD, was reported below the 10-20 fg/m3 detection limit for most of the ambient air samples selected for analysis. PMID- 1627324 TI - Effects of operating variables on PAH emissions and mutagenicity of emissions from woodstoves. AB - As part of the Integrated Air Cancer Project, the U.S. Environmental Protection Agency (EPA) has conducted field emission measurement programs in Raleigh, North Carolina, and Boise, Idaho, to identify the potential mutagenic impact of residential wood burning and motor vehicles on ambient and indoor air. These studies included the collection of emission samples from chimneys serving wood burning appliances. Parallel projects were undertaken in instrumented woodstove test laboratories to quantify woodstove emissions during operations typical of in house usage but under more controlled conditions. Three woodstoves were operated in test laboratories over a range of burnrates, burning eastern oak, southern yellow pine, or western white pine. Two conventional stoves were tested at an altitude of 90 m. One of the conventional stoves and a catalytic stove were tested at an altitude of 825 m. Decreasing burnrate increased total particulate emissions from the conventional stoves while the catalytic stove's total particulate emissions were unaffected. There was no correlation of total particulate emissions with altitude whereas total polynuclear aromatic hydrocarbon (PAH) emissions were higher at the lower altitude. Mutagenicity of the catalytic stove emissions was higher than emissions from the conventional stove. Emissions from burning pine were more mutagenic than emissions from oak. PMID- 1627325 TI - Endomyocardial biopsy of normal donor hearts before cardiac transplantation. A morphological and morphometrical study in 97 cases. AB - Endomyocardial biopsies from 97 normal donor hearts were examined. Morphometric analysis showed: mean myocyte diameter 22.21 +/- 6.93 mu, mean nuclear dimension 7.32 +/- 2.33 mu, mean nuclear/sarcoplasmic ratio 0.33 +/- 0.02. 31 biopsies showed enlarged myocytes (mean diameter 31.65 +/- 3.98 mu) with increased nuclear size (mean 10.45 +/- 1.39 mu), but preserved nuclear/sarcoplasmic ratio (mean 0.33 +/- 0.01). The mean age of these latter subjects was significantly higher. Endocardial thickness mean value was 17.73 +/- 4.58 mu, but in 28 cases the value exceeded the considered upper normal limit of 20 mu. Interstitial mononuclear cells were rare and randomly present. Interstitial fibrosis was observed in 15% and focal fibrosis in 27% of cases. Our results show that histology of biopsies from clinically normal hearts can widely vary, sometime overriding the pathologic boundaries. These apparently "benign" abnormalities should be kept in mind when specific pathologic substrates of cardiac diseases have to be defined. PMID- 1627326 TI - Marfan syndrome with aortic dissection and triple-barrel aorta. AB - A case of Marfan syndrome with spontaneously and subsequently developed dissections of the aorta, one in the form of triple-barrel aorta, three times corrected by grafts is described. The autopsy revealed "healed" and acute dissections in almost the entire aorta outside the grafts. "Healed" thoracoabdominal dissection had true lumen (with entry and re-entry intimal tears), and old false lumen and in addition in its distal portion of a triple barrel aorta was formed (dissection of healed aortic dissection). Lethal adventitial rupture occurred in the portion with an old false lumen. Dissection of the left subclavian artery, the right common carotid artery, resulting in saccular aneurysm, and avulsion of the right renal artery were also found. PMID- 1627327 TI - AIDS and the heart in the Caribbean: a silent entity. PMID- 1627328 TI - Aortic aneurysm at autopsy: a five year survey in Hong Kong. AB - The authors reviewed 3133 consecutive autopsies performed in the 5 year period from 1986 to 1990 in Queen Mary Hospital (Hong Kong), and 96 cases of aortic aneurysms were found. The incidence was 1 in 33 autopsies. The ratio of male to female was 1.8 to 1, and the disease was most common in the eighth decade of life. The majority of death was due to rupture (70%) or related atherosclerotic diseases (14%), and the majority of aneurysms were not suspected before autopsies (62%). Most of the non-dissecting aneurysms were found in the abdominal aorta, the infra-renal portion. For dissecting aneurysms, Daily's type A was much more common. Hypertension was recognized in a high proportion of cases. Accompanying diseases like syphilis, Takayasu's disease, ischemic heart disease, cerebrovascular accident, diabetes mellitus, peripheral vascular disease, and chronic obstructive airway disease were also noted. PMID- 1627329 TI - Vasculopathic and cardiomyopathic changes induced by low-protein high carbohydrate tapioca based diet in bonnet monkey. Vasculopathic and cardiomyopathic changes in induced malnutrition. AB - Mucoid vasculopathy is an entity characterized by a generalized mucopolysaccharidosis of blood vessels. It has been observed in patients from our Institute. Bonnet monkeys (Macaca radiata) were given low-protein normal carbohydrate and low-protein high-carbohydrate tapioca based diets for experimental periods of 3 or 5 months. The latter diet is similar to that consumed by people from this part of India (Kerala) where mucoid vasculopathy is observed. Vascular lesions were seen in all test animals as a generalized mucopolysaccharidosis and as hyperplastic changes in intimal and medial smooth muscle cells. In 6/31 animals gross cardiac lesions were found. They consisted of biventricular hypertrophy and atrophy owning to myopathic changes and endocardial thickening. The cardiovascular lesions were enhanced in animals that received low protein high-carbohydrate diet for a longer period. Our experiments established an etiologic role for diet, especially protein deficiency, in the induction of both vascular and cardiac changes. PMID- 1627330 TI - Recurrent cervical squamous cell carcinoma presenting with cardiac tamponade. Recurrent cervical carcinoma-tamponade. AB - Cervical squamous cell carcinoma rarely metastasizes to the heart, and cardiac tamponade secondary to pericardial involvement has been only rarely reported. We describe a case of recurrent cervical squamous cells carcinoma presenting with cardiac tamponade secondary to extensive pericardial metastases. The patient, a 38-year old woman, initially presented with Stage IIIB cervical squamous cell carcinoma. She responded well to radiation and chemotherapy, there was no clinical or radiographic evidence of persistent disease after the initial therapy. Sixteen months after presentation, she developed shortness of breath and chest pain. The patient received additional chemotherapy; however, she died 17 months after her initial presentation. At autopsy, metastatic keratinizing squamous cell carcinoma extensively involved the pericardium and superficial myocardium. This case illustrates the unusual occurrence of recurrent cervical squamous carcinoma presenting with cardiac dysfunction secondary to pericardial metastases. PMID- 1627331 TI - Post-ischemic rupture of the anterior papillary muscle of the right ventricle associated with persistent pulmonary hypertension of the newborn: a case report. AB - We report the case of a six-day-old male infant exposed in utero to a prostaglandin synthetase inhibitor, who presented pulmonary arterial hypertension, tricuspid insufficiency, and electrocardiographic signs of diffuse myocardial ischemia. The necropsy showed organizing infarction of the anterior and posterior right papillary muscles (probably occurred in utero) with complete rupture of the former, besides abnormal muscularization of the intraacinar pulmonary arterioles (persistent fetal circulation of the newborn). The authors suggest a possible relation between the myocardial ischemic and pulmonary hypertensive lesions since the prostaglandin synthetase inhibitor can induce precocious pulmonary arteriolar muscularization and constriction of the arterial duct, leading to right ventricular overload, thus facilitating the occurrence of papillary and subendocardial ischemia. PMID- 1627332 TI - Fatal lipoma of the heart. AB - The clinical and postmortem findings of the largest cardiac lipoma reported to this date are described. Emphasis is made on the symptoms of respiratory embarrassment that were prominent in this fatal case. PMID- 1627333 TI - An unusual expression of a squamous cell marker, small proline-rich protein gene, in tracheobronchial epithelium: differential regulation and gene mapping. AB - An unusual expression of a putative squamous cell marker, small proline-rich protein (spr1), in mucociliary epithelial cells of conducting airways was demonstrated in a serum-free culture system. A cDNA clone was isolated from the cDNA library of monkey tracheobronchial epithelial (TBE) cells by differential hybridization. This cDNA clone, MT5, exhibited 98% homology to a DNA sequence obtained from human keratinocytes treated with either UV light or phorbol esters (T. Kartasova et al., 1988, Mol. Cell. Biol. 8:2195-2230). The predicted peptide of MT5 is unusual for its high content of proline (29%), glutamine (18%), and cysteine (9%) and its repeated PKVPEPC units. The level of spr1 mRNA in cultured cells was inhibited more than 90% by vitamin A. In contrast, phorbol 12-myristate 13-acetate (PMA) stimulated the level of spr1 mRNA by 3- to 8-fold. This differential regulation coincided with the effects of these chemicals on the cornification of cultured TBE cells. Using MT5 as a probe, we have localized the tracheal spr1 gene on the human chromosome 1 by a Southern blot analysis using a panel of human-rodent somatic cell hybrid DNAs. The gene was further sublocalized to bands q22-23 by in situ hybridization. PMID- 1627334 TI - Modulation of neutrophil and mononuclear cell adherence to bronchial epithelial cells. AB - Neutrophils and mononuclear cells have been associated with the lower respiratory tract inflammation observed in both acute and chronic bronchitis. In order to transit into and remain within the airways, neutrophils and mononuclear cells would likely need to adhere to bronchial epithelium. To test this hypothesis, bovine bronchial epithelial cells (BBECs) were isolated and cultured on a round coverslip. After 7 to 10 days, 51Cr-labeled neutrophils and mononuclear cells were evaluated for their capacity to adhere to the BBEC monolayer. Both neutrophils and mononuclear cells readily bound to the BBEC monolayer (10.8 +/- 1.2% bound neutrophils; 40.5 +/- 2.8% bound mononuclear cells). Stimulation of the neutrophils and mononuclear cells with phorbol 12-myristate 13-acetate (PMA) increased the adherence (45.8 +/- 10.6% bound neutrophils, P less than 0.01 compared with unstimulated cells; 58.7 +/- 6.2% bound mononuclear cells, P less than 0.01 compared with unstimulated cells). Importantly, stimulating the BBEC monolayer with PMA, bacterial lipopolysaccharide, or a cigarette smoke extract for 4 to 72 h also increased the adherence of both cell types (P less than 0.01, all comparisons at 24 h). The adherence was not decreased by exposure of either the BBEC monolayer, the neutrophils, or the mononuclear cells to cycloheximide or to the anti-CD11/CD18 monoclonal antibody 60.3 (P greater than 0.05). However, exposure of the BBEC monolayer to trypsin before addition of the neutrophils significantly decreased adherence (P less than 0.05). Because neutrophils and mononuclear cells are thought to mediate cell cytotoxicity by adhering to the target cells, BBECs were labeled with 51Cr, and 51Cr release was measured as an index of cytotoxicity. There was a modest increase in 51Cr release by the addition of unstimulated neutrophils and mononuclear cells, and culturing the BBEC monolayer with PMA before the addition of the neutrophils or mononuclear cells resulted in a further modest enhancement of 51Cr release (P less than 0.05). Similar results were obtained using lactate dehydrogenase release as a measure of cytotoxicity. These results demonstrate that inflammatory cells can adhere to BBECs and may be capable of mediating cytotoxicity and adherence and cytotoxicity can be increased by stimulating BBECs. PMID- 1627335 TI - Homeobox 1.3 expression: induction by retinoic acid in human bronchial fibroblasts. AB - Homeobox (Hox) genes code for transcriptional factors and are expressed during many developmental and differentiative processes. In this study, we describe the induction of Hox 1.3 expression by retinoic acid (RA) in human bronchial fibroblasts (HBF) derived from explants of bronchial tissue. Using Northern blot analysis, we show that RA induces Hox 1.3 mRNA 3- to 10-fold over steady-state levels within 2 h after addition of RA to HBF culture medium. The induction was dose dependent, reaching a half-maximal level at approximately 10(-8) M RA. This induction was not seen in human dermal fibroblasts. Immunofluorescent staining of HBF showed a corresponding increase in Hox 1.3 protein levels in the nuclei. The increase in Hox 1.3 transcript levels in HBF was not abolished by cycloheximide treatment, suggesting that synthesis of a protein intermediate is not required for the induction. RA did not significantly alter the rate of degradation of the Hox 1.3 mRNA as determined by actinomycin D treatment, suggesting that the increase in Hox 1.3 mRNA may be due to an increase in the rate of transcription. This study provides further evidence that bronchial fibroblasts are targets for RA. Although downstream target genes for Hox 1.3 have not yet been identified, it is likely that the induction of Hox 1.3 by RA is an early step in a cascade of RA induced changes in gene expression in bronchial fibroblasts. PMID- 1627336 TI - Transient ultrastructural injury and repair of pulmonary capillaries in transplanted rat lung: effect of preservation and reperfusion. AB - A donor lung is injured during preservation and is generally thought to be further injured by reperfusion on transplantation. Donor lungs from 15 adult male Lewis rats preserved by flush perfusion with cold Marshall's solution at 4 degrees C were examined by scanning and by quantitative transmission electron microscopy after 2, 4, or 7 h of storage at 4 degrees C and after transplantation (syngeneic) at 4 or 12 h (six animals per time interval). During preservation of the donor lung, capillary morphology changed rapidly. Both endothelial cells and type I pneumonocytes thinned (surface/volume ratio increased by 2 h in both; P less than 0.001). Pericapillary edema developed involving the blood-gas barrier. Basement membrane thickness increased significantly (P less than 0.001). Occasional breakage of the endothelial cell sheet occurred after 4 h of preservation, but even after 7 h of preservation there was no evidence of irreversible cell damage. The lamellar bodies of type II pneumocytes aggregated. Changes increased in severity with increase in preservation time. After transplantation, type I and type II pneumonocytes recovered after 12 h, but it took longer for the endothelial cell morphology to recover. Edema decreased rapidly during the first 4 h, despite the number of adherent neutrophils increasing 3-fold. The pulmonary capillaries of the transplanted lung showed no structural evidence of additional reperfusion injury, indicating a satisfactory method of preservation. PMID- 1627337 TI - Interleukin-2 directly increases albumin permeability of bovine and human vascular endothelium in vitro. AB - The direct effects of interleukin-2 (IL-2) on albumin permeability of cultured bovine pulmonary artery endothelial cell (BPAEC) and human arterial endothelial cell (HAEC) monolayers were studied. BPAEC were exposed to IL-2 (500 to 25,000 U/ml) for 4 h. The steady-state transfer rate of [125I]albumin across the BPAEC monolayer was 3.3 +/- 0.4%/h (n = 10) in control BPAEC (diluent alone), was significantly increased in BPAEC exposed to 500 U/ml of IL-2 (72 +/- 3% above control values, n = 6, P less than 0.02), and further increased in BPAEC exposed to 5,000 U/ml (60 +/- 2% increase above 500 U/ml values, n = 5, P less than 0.02). No further increase was noted after exposure to 25,000 U/ml of IL-2. Additionally, no further increase in [125I]albumin transfer rates was noted in BPAEC exposed to 5,000 U/ml of IL-2 for 24 versus 4 h. Similar changes were found using HAEC. Preincubation of HAEC with an anti-IL-2 low-affinity receptor antibody (anti-IL-2R alpha) inhibited the IL-2-induced permeability increase. Expression of IL-2R alpha receptors in HAEC incubated with 5,000 U/ml of IL-2 for 4 h was also found. Thus, IL-2 appears to have a direct effect on cultural arterial endothelial monolayers not requiring the presence of other cell types or serum proteins. IL-2-induced increases in endothelial macromolecular permeability may play an important role in the pathogenesis of the IL-2-induced vascular leak syndrome seen in vivo. PMID- 1627339 TI - [Statistical aspects of the methodology of investigation: a critical situation]. PMID- 1627338 TI - Antioxidant defense mechanisms in cultured pleural mesothelial cells. AB - The role of different antioxidant pathways in cultured rat pleural mesothelial cells was studied by exposing the cells to various hydrogen peroxide (H2O2) concentrations and by measuring H2O2 cell cytotoxicity and the capacity of the cells to scavenge H2O2. The antioxidant enzymes, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, and catalase were analyzed biochemically. Catalase and CuZn superoxide dismutase were localized by immunocytochemistry. To enable investigation of the glutathione redox cycle and catalase pathways, glutathione reductase was inactivated with 1,3-bis(2 chloroethyl)-1-nitrosourea (BCNU) and catalase was inactivated with aminotriazole. When the cells were exposed to a low, sublethal (0.030 mM) H2O2 concentration, glutathione reductase but not catalase inactivation resulted in a decreased capacity to remove H2O2 from the extracellular medium. When the cells were exposed to a high (0.25 mM) H2O2 concentration, H2O2-scavenging capacity decreased remarkably when catalase was inactivated. When the cells were exposed to 0.1 to 0.5 mM H2O2, cell cytotoxicity (lactate dehydrogenase release) increased significantly if glutathione reductase was inactivated; catalase inactivation resulted in a significant cytotoxicity only at high (greater than or equal to 0.25 mM) H2O2 concentrations. Immunocytochemical studies showed that the cells, both in situ and in vitro, contained low amounts of catalase. This suggests that the results of the catalase-inhibition studies are probably not due to a change in the characteristics of the cells in culture. 3-Aminobenzamide is a compound that is known to prevent NAD depletion through inhibition of poly(ADP ribose) polymerase during oxidant stress. When intact cells were treated with different antioxidants and exposed to 0.5 mM H2O2, both catalase and 3 aminobenzamide protected the cells completely.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627340 TI - [Epidemiologic study of post-traumatic epilepsy on the Island of Majorca]. AB - The epidemiological study of post-traumatic epilepsy after 10 years of follow-up on the island of Mallorca is reported. The double prospective and retrospective method was used for patient selection. Prospectively, 23,082 isolated head injuries were studied in the Hospital of Son Dureta in Palma de Mallorca between the years 1980 to 1988. Retrospectively, 663 epileptics proceeding from different data bases of different centers were studied. Two hundred and twelve post traumatic epilepsies of certain etiology were identified. Results are discussed with regard to age, sex and latency time found. Special emphasis is made in that benign cerebral concussion is not causing seizures. A prevalence of 4% of post traumatic epilepsy is found in the population of risk head injuries, and post traumatic epilepsy represents 7% of the total of the casuist of epileptic patients. PMID- 1627341 TI - [Morphologic and morphometric study of the superficial peroneal nerve. Use of material from autopsies and amputations]. AB - A series of 100 human peroneal nerves proceeding from autopsies and amputations were studied by histologic and morphometric techniques with a qualitative and quantitative analysis of each being performed following the morphological criteria of Dick et al (1985). After evaluating the results the authors consider that the peripheral nerve proceeding from autopsies and amputations is useful for basic morphologic study providing it is adequately processed within the first 29 hours post-mortem and post-amputation. Previous studies demonstrating the existence of minimum morphological alterations in normal nerves is corroborated. In order to perform a correct morphological evaluation of the peripheral nerve a mere qualitative analysis is not sufficient but rather statistically evaluated quantitative parameters must be employed. PMID- 1627342 TI - [Prenatal diagnosis of Lesch-Nyhan syndrome]. PMID- 1627343 TI - [Natural history of a bilateral carotid dissection]. AB - The coexistence of arterial dissection in several cervical vessels is exceptional and is usually an accidental finding detected upon performance of an extensive angiographic examination in patients with unilateral manifestations. The absence of previous clinical manifestations related with asymptomatic vessel dissection impedes the knowledge of the time between the different dissections. The case of a bilateral carotid dissection (CD) is presented in which the clinical course permitted the authors to know the interval between both dissections. The patients initially presented manifestations of right CD and, at 15 days, an ictus due to left CD in which the presence of right unilateral asterixis was of note. The time span between both dissections was established as 12-15 days. PMID- 1627344 TI - [Dystonia sensitive to levodopa]. AB - A Spanish family with the DTI variant sensitive to L-Dopa is presented with three patients, 2 first cousins and an aunt being described. The dystonic beginning of the disease during infancy is of note in the former two patients as is the later initiation of parkinsonism in the third patient. Marked improvement was observed in all of the patients with L-Dopa treatment. Some peculiarities of the cases are commented upon and the discussion includes analysis of the nosological aspects, relation with juvenile parkinsonism and Parkinson's disease. Finally, reference is made to the different hypersensitivity for presenting choreic dyskinesia which the patients had. PMID- 1627345 TI - [Ischemic ictus in a young woman with fibromuscular dysplasia of the basilar artery]. AB - Fibromuscular dysplasia (FMD) is a vasculopathy of unknown etiology generally presented in young women and preferentially found in the renal arteries. The second site of frequency of appearance corresponds to the cervical-cephalic arteries with cases of the intracranial vessels being exceptional. We recently had the opportunity to study a female patient of 29 years of age admitted following an acute progressive cerebrovascular event. Cranial computerized tomography (CT) demonstrated multiple ischemic lesions bilaterally affecting the basilar-vertebral territory. Angiographic study established the diagnosis of FMD upon observing "pearl-like" lesions located in the distal part of the basilar artery. Anticoagulant treatment was initiated and the patient evolved satisfactorily although some neurologic deficits persisted. The authors insist on the need to consider FMD as a cause of ictus in young, specially female, patients. PMID- 1627346 TI - [Trigeminal neuralgia secondary to an intraventricular tumor]. PMID- 1627347 TI - [Acute hemichorea-hemiballism in active pulmonary tuberculosis]. PMID- 1627348 TI - [Ischemic cranial polyneuritis secondary to arteritis of the temporal artery]. PMID- 1627349 TI - Effect of diazepam on the fatty acid composition of plasma and liver phospholipids in rat. AB - Male Wistar rats (2 months old) were maintained on a nutritionally adequate diet, and diazepam was administered at a dose of 10 mg/kg/day. After 24 weeks the effects on the fatty acid composition of plasma and liver phospholipids were studied. Increased levels of palmitic (16:0), palmitoleic (16:1n-7), stearic (18:0), and oleic (18:1n-9) acids were found in plasma phospholipids. In contrast, the levels of docosapentanoic (22:5n-3) and docosahexanoic (22:6n-3; DHA) acids were drastically decreased by diazepam. A significant decrease produced by diazepam was also found in levels of DHA in liver phospholipids. PMID- 1627350 TI - In vitro effects of glycosylated insulin in perfused liver and hindquarter in rats. AB - Using the perfused liver and hindquarter of the rat, the uptake of glycosylated insulin and its effect on glucose output were investigated. Insulin was glycosylated in ambient high glucose concentration, and glycosylated insulin GI80 (insulin incubated with 0.08% glucose), GI350 (incubated with 0.35% glucose), and GI1000 (incubated with 1% glucose) were prepared. The liver and hindquarter were perfused with nonglycosylated insulin (N-GI) or glycosylated insulin at a concentration of 100 or 1000 microU/ml. There were no significant differences in the fractional uptake of insulin by perfused liver and hindquarter despite glycosylation. Insulin-induced decrement in glucose output was significantly lower in the liver perfused with GI1000 than that in the liver perfused with N GI, GI80, and GI350 at an insulin concentration of 100 microU/ml. There were no significant differences in insulin-induced decrement in glucose output between the hindquarter perfused with N-GI, GI80, GI350, and GI1000. These results suggest that when insulin (100 microU/ml) is incubated with a markedly elevated concentration of glucose (1000 mg/dl) its biological activity is reduced in the liver, but not in the hindquarter. PMID- 1627351 TI - Hurler syndrome: a patient with abnormally high levels of alpha-L-iduronidase protein. AB - Mucopolysaccharidosis type I (MPS I: McKusick 25280) is a clinically heterogenous lysosomal storage disorder which is caused by a variable deficiency in alpha-L iduronidase activity (alpha-L-iduronide iduronohydrolase, EC 3.2.1.76). Cultured fibroblasts from an MPS I patient (cell line 2827) with a severe clinical phenotype (Hurler syndrome) have been characterized using immunochemical and biochemical techniques. Using a specific immunoquantification assay, we have demonstrated that cell line 2827 had an alpha-L-iduronidase protein content (189 ng/mg of extracted cell protein) at least six times greater than the mean level found in normal control fibroblasts (30 ng/mg of extracted cell protein). This was the only MPS I cell line, from a group of 23 MPS I patients, that contained greater than 7% of the mean level of alpha-L-iduronidase protein detected in normal controls. Cell line 2827 had very low alpha-L-iduronidase activity toward the fluorogenic substrate 4-methylumbelliferyl-alpha-L-iduronide, and a radiolabeled disaccharide substrate derived from heparin. Maturation studies of alpha-L-iduronidase in cell line 2827 showed apparently normal levels of alpha-L iduronidase synthesis with delayed processing to the mature form. Subcellular fractionation experiments demonstrated alpha-L-iduronidase protein in lysosomal enriched fractions isolated from cell line 2827, suggesting a normal cell distribution and supporting the proposed delayed processing. It is proposed that the MPS I patient described has an alpha-L-iduronidase gene mutation which affects both the active site and post-translational processing of the enzyme. This mutation must be structurally conservative because it does not result in instability either during maturation or in the lysosome. PMID- 1627352 TI - Methylenetetrahydrofolate reductase (MR) deficiency: thermolability of residual MR activity, methionine synthase activity, and methylcobalamin levels in cultured fibroblasts. AB - Methylenetetrahydrofolate reductase (MR) deficiency is the most common inborn error of folate metabolism with more than two dozen patients described. The phenotypic spectrum ranges from severe neurological deterioration and early death to asymptomatic adults. Some patients with a severe deficiency of MR have been shown to have thermolabile reductase at 55 degrees C. Since methyltetrahydrofolate, the product of MR, is a methyl donor for methylcobalamin (MeCbl), the cofactor for methionine synthase (MS), we have looked at MeCbl accumulation and MS activity in fibroblasts from 15 patients with MR deficiency. Thermolabile MR was most often but not always seen in later onset disease. MeCbl levels were often lowest in the patients with early onset disease. All but two patients had levels of methionine synthase within the control range. PMID- 1627353 TI - Influence of calcium antagonists on thrombin-induced calcium mobilization and platelet-vessel wall interactions. AB - Elevation of cytosolic ionized calcium plays a critical role in human platelet activation. We have evaluated three well-characterized calcium antagonists for their ability to prevent thrombin-induced calcium mobilization in Fura 2 AM loaded platelets and also their ability to inhibit platelet-vessel wall interactions. Thrombin (0.2 U/ml) caused significant elevation of cytosolic calcium (basal 84 +/- 18, activated 546 +/- 76 nM; n = 3). Verapamil, diltiazem, and nifedipine (100 microM) did not exert any inhibitory effect on thrombin mediated calcium elevation. Untreated platelets perfused through a Baumgartner chamber containing a rabbit aorta preparation reacted with exposed and denuded subendothelium. The percentage of the total area covered by control platelet thrombi was 39.6 +/- 3.4. Diltiazem and Nifedipine significantly reduced the percentage of area covered by platelet thrombi, but the drugs were not as effective as aspirin (8.2 +/- 1.4). Calcium antagonists studied did not inhibit thrombin-stimulated elevation of cytosolic calcium in blood platelets. Although these drugs have been shown to prevent in vitro platelet aggregation and offer some protection against risks for atherosclerosis and thrombosis, they failed to significantly inhibit platelet-vessel wall interactions leading to formation of spread platelets and aggregates. PMID- 1627354 TI - Purification and properties of AMP-deaminase from human kidney. AB - AMP-deaminase from human kidney (cortex and medulla) was purified and the physicochemical properties were characterized. The enzyme from both portions of the kidney exhibited identical kinetics and regulatory properties. At optimal pH (6.6), the AMP-deaminase studied exhibited a distinctly sigmoidal substrate saturation kinetics, with the half-saturation parameter (S0.5) as high as 10 mM. ATP at 1 mM strongly activated the enzyme, decreasing S0.5 nearly 10-fold. The activating effect of ADP was less strong. Orthophosphate inhibited the enzyme, but the inhibition observed was weak (Ki approximately 16 mM) and had a pure competitive character. At pH 7.2, physiological for the kidney cortex, orthophosphate inhibition became even weaker and became partially competitive. Variations in the adenylate energy charge had potent effects on the activity of AMP-deaminase, depending on the size of the total adenine nucleotide pool examined. The results of gel filtration and SDS-PAGE indicated that human kidney AMP-deaminase is an oligomeric enzyme composed of four, probably identical, subunits weighing about 37 kDa each. PMID- 1627355 TI - Heterogeneity in cblG: differential retention of cobalamin on methionine synthase. AB - Cultured fibroblasts from patients with functional methionine synthase deficiency have been shown to belong to two complementation classes, cblE and cblG. Both are associated with decreased intracellular levels of methylcobalamin (MeCbl) and decreased incorporation of label from 5-methyltetrahydrofolate into macromolecules. Methionine synthase specific activity is normal or near normal in cell extracts from cblE patients under standard reducing conditions, whereas specific activity is low in cblG extracts. Seven of 10 cblG cell lines accumulated [57Co]CN-Cbl equivalent to control cells and showed similar proportions of label associated with the two intracellular cobalamin binders, methionine synthase and methylmalonyl-CoA mutase. The remaining three cblG lines showed reduced accumulation of labeled Cbl and virtually none associated with methionine synthase. The specific activity of methionine synthase was decreased in cell extracts from both cblG subgroups, being almost undetectable in extracts from the latter three lines. Incorporation of label from [14C]MeTHF into either macromolecules or into methionine was decreased in both cblG groups, but was paradoxically higher in the three lines with very low in vitro methionine synthase activity. These results demonstrate further heterogeneity within cblG and suggest that the defect in the three variant lines affects the ability of methionine synthase to retain Cbl. PMID- 1627356 TI - Screening for gene deletions and known mutations in 13 patients with ornithine transcarbamylase deficiency. AB - We analyzed DNA from 13 males with ornithine transcarbamylase (OTC) deficiency for gene deletions and known point mutations using the polymerase chain reaction (PCR), allelle-specific oligonucleotide (ASO) hybridization, and Southern blotting with full-length OTC cDNA and exon-specific probes. Three patients were found to have deletions: one was missing the whole OTC gene; a second patient had a deletion of both exon 7 and 8; and the third had a deletion of exon 9. Only one of the remaining 10 patients had a known point mutation consisting of a G-to-A change in nucleotide 422 of the sense strand resulting in a glutamine substitution for arginine at amino acid 109 of the mature OTC protein. This study describes the integration of various molecular methods to screen OTC-deficient patients for deletions and points mutations. Two new deletions within the OTC gene are described. PMID- 1627357 TI - Sulfate transport in normal and cystic fibrosis fibroblasts. AB - The glycoconjugate component of cystic fibrosis (CF) epithelial secretions is abnormally sulfated. Previous studies have suggested that some but not all CF fibroblasts express this secondary defect. We tested the hypothesis that the major CF mutation (delta F508/delta F508) is correlated with elevated sulfate transport, by measuring the rates of saturable and nonsaturable [35S]SO4(2-) uptake in skin fibroblasts isolated from CF patients of known genotype. No significant differences were apparent between normal and CF fibroblasts. PMID- 1627358 TI - Characterization of human genomic yeast artificial chromosome inserts containing hexokinase 1 coding information on chromosome 10. AB - Hexokinase 1 (HK1) is one of four mammalian HK isoenzymes and maps to human chromosome 10. Two yeast artificial chromosomes (YACs) were identified in the Washington University human YAC library using polymerase chain reaction (PCR) primers designed with knowledge of the human HK1 cDNA sequence. YAC B129B12 is 120 kb in length and maps entirely to chromosome 10. YAC A159D5 is 400 kb in length and appears to have resulted from a recombination of chromosome 10 with non-chromosome 10 material. We report these YACs as potential resources for those interested in HK1 gene organization and mapping, as well as those desiring additional genomic information and markers on chromosome 10. PMID- 1627359 TI - Inhibitory effect of demoxepam on tryptophan binding to rat hepatic nuclei. AB - Since some patients with eosinophilia-myalgia syndrome ingested tryptophan along with benzodiazepines, we investigated whether demoxepam, the N-desalkylated compound of chlordiazepoxide, would influence the binding of tryptophan to hepatic nuclei. L-Tryptophan has been shown to bind (saturable, stereospecific, and of high affinity) to rat hepatic nuclei and nuclear envelopes. We report that demoxepam has an inhibitory effect on in vitro [3H]tryptophan binding to rat hepatic nuclei and has an apparent KD approximately 22 microM. PMID- 1627360 TI - Abnormal hepatic nucleotide pools in sparse fur (spf) mutant mice deficient in ornithine transcarbamylase. AB - Sparse fur hemizygous male mice are over 90% deficient in ornithine transcarbamylase and exhibit increased synthesis of orotic acid. Because our earlier studies have demonstrated that orotic acid is a liver tumor promoter in the rat, it was of interest to determine whether this genetic disorder also increases the risk of tumor promotion. The results revealed that the livers of mutant mice showed a fourfold increase in uridine nucleotides and a 50% decrease in adenosine nucleotides compared to corresponding controls, a pattern of nucleotide pool imbalance similar to that seen in the livers of rats exposed to orotic acid under promoting conditions. Creation of such an imbalance appears to be important for orotic acid to exert its promotional effects. Sparse fur mutant mouse may, therefore, be an ideal animal model to study the tumor-promoting effects of orotate. PMID- 1627361 TI - Moniliformin: the result of storing a citric acid cycle intermediate. PMID- 1627362 TI - Double-minute chromosomes as megabase cloning vehicles. AB - Radiation-reduced chromosomes provide valuable reagents for cloning and mapping genes, but they require multiple rounds of x-ray deletion mutagenesis to excise unwanted chromosomal DNA while maintaining physical attachment of the desired DNA to functional host centromere and telomere sequences. This requirement for chromosomal rearrangements can result in undesirable x-ray induced chromosome chimeras where multiple non-contiguous chromosomal fragments are fused. We have developed a cloning system for maintaining large donor subchromosomal fragments of mammalian DNA in the megabase size range as acentric chromosome fragments (double-minutes) in cultured mouse cells. This strategy relies on randomly inserted selectable markers for donor fragment maintenance. As a test case, we have cloned random segments of Chinese hamster ovary (CHO) chromosomal DNA in mouse EMT-6 cells. This was done by cotransfecting plasmids pZIPNeo and pSV2dhfr into DHFR-CHO cells followed by isolation of a Neo + DHFR + CHO donor colony and radiation-fusion-hybridization (RFH) to EMT-6 cells. We then selected for initial resistance to G418 and then to increasing levels of methotrexate (MTX). Southern analysis of pulsed-field gel electrophoresis of rare-cutting restriction endonuclease digestions of DNA from five RFH isolates indicated that all five contain at least 600 kb of unrearranged CHO DNA. In situ hybridization with the plasmids pZIPNeo and pSV2dhfr to metaphase chromosomes of MTX-resistant hybrid EMT-6 lines indicated that these markers reside on double-minute chromosomes. PMID- 1627363 TI - Quantitative analysis of DNA-sequencing electrophoresis. AB - At the heart of the DNA-sequencing process is a remarkably selective electrophoretic separation of up to 1000 oligonucleotide fragments, each differing in size by only a single nucleotide unit. A quantitative analysis of this separation is performed in terms of both selectivity and efficiency. It is shown that both the Ogston sieving and reptation migration mechanisms are operative. It is demonstrated that, under the conditions used in traditional sequencing electrophoresis, Joule heating does not significantly contribute to band broadening, and that diffusion is the primary contributor to plate height. An analytic expression is derived relating the peak width for each fragment to its molecular size. Calculations are presented showing that, when longer sequences are required, the maximum electrical field strength will be limited by the influence of biased reptation on the separation selectivity. Finally, it is shown that, when short sequences are required, the electrical field strength is limited by the ability to dissipate Joule heat, and that in these cases a tube format will be approximately 50% faster than a slab having a thickness equivalent to the tube diameter. PMID- 1627364 TI - Sequential cisplatin--doxorubicin, early debulking in advanced ovarian cancer. PMID- 1627365 TI - Low-dose radiation carcinogenesis. PMID- 1627366 TI - EC proposal for directive can destroy the possibilities of cancer research. PMID- 1627367 TI - Axillary surgery in breast cancer--is there still a debate? PMID- 1627368 TI - Doxorubicin in advanced breast cancer: influence of schedule on response, survival and quality of life. AB - The influence of scheduling of doxorubicin on response, survival and quality of life was assessed in a randomised trial in patients with advanced breast cancer, none of whom had previously received cytotoxic chemotherapy for advanced disease. 28 patients received 75 mg/m2 doxorubicin every 3 weeks for four courses (arm 1) and 31 patients received 25 mg/m2 weekly for 12 courses (arm 2). Response rates and median time to progression were similar in the two arms and median survival was 8 months in both arms. However, amongst patients receiving treatment every 3 weeks, psychological distress measured using the Rotterdam symptom checklist fell significantly over the course; no such change was observed in those treated weekly. Physical symptoms related to cancer improved during treatment similarly for both groups. PMID- 1627369 TI - Continuous infusion of recombinant interleukin-2 with or without autologous lymphokine activated killer cells for the treatment of advanced renal cell carcinoma. AB - Data have been analysed for 327 patients with advanced renal cell carcinoma receiving a continuous infusion of recombinant interleukin 2 (rIL-2) alone (225 patients) or rIL-2 plus lymphokine activated killer (LAK) cells (102) on a normal oncology ward. Eligibility criteria were uniform across protocols, all patients having advanced progressive disease, but with an ambulatory performance status. The baseline characteristics of patients receiving rIL-2 alone did not differ significantly from those receiving LAK, with the exception that the LAK treated patients had a better performance status. Despite similar treatment intensity, toxicity was more severe in the patients receiving LAK. The addition of LAK did not lead to higher response rates or to prolonged response duration, progression free survival or survival. This review confirms the activity of rIL-2 for the treatment of advanced renal cell carcinoma and demonstrates that the addition of LAK cells does not lead to increased efficacy. PMID- 1627370 TI - Phase II study of continuous subcutaneous interferon-alfa combined with cisplatin in advanced malignant melanoma. AB - Interferon-alfa (IFN-alpha) and cisplatin have shown synergism in vitro against tumour cell lines and optimal effects were observed with continuous and high IFN concentration. 20 patients with advanced malignant melanoma were treated with 10 MU IFN subcutaneously continuously, daily, plus cisplatin 50 mg/m2 intravenously on days 8 and 9. Cisplatin was repeated every 4 weeks. The main toxic effects were myelosuppression, fatigue and weight loss. Toxicities always resolved completely after reduction/interruption of IFN and no life-threatening infection was observed. There were 1 complete and 6 partial responses. 6 patients had stable disease. Median time to progression was 7 months with a range of 16 to 2 months. The combined regimen of IFN-alpha and cisplatin is active in patients with multiple visceral and skeletal sites. PMID- 1627371 TI - Sequential interleukin-2 and alpha interferon for renal cell carcinoma and melanoma. AB - There is a theoretical basis for the synergy of interleukin-2 (IL-2) with other cytokines. We have investigated sequential treatment with IL-2 and alpha interferon. 1 of 22 patients with metastatic renal cell carcinoma had a partial response and one a minimal response to continuous infusion IL-2 but none of the 9 patients with melanoma responded. 16 of 17 patients with renal cell cancer, and 8 with melanoma, were then treated with alpha interferon. 2 patients with renal cell cancer responded to alpha interferon with sustained remissions of 30 and 40 months; both had responded to IL-2. The investigation of combination therapy with other cytokines is suggested, by these unusually long responses to alpha interferon. PMID- 1627372 TI - Phase I study comparing continuous infusion of recombinant interleukin-2 by subcutaneous or intravenous administration. AB - 22 cancer patients entered a randomised phase Ib trial comparing the effects of low-dose recombinant interleukin-2 (300 micrograms/m2, approximately equivalent to 6.4 x 10(6) cetus units or 38 x 10(6) U per day) given continuously by intravenous or subcutaneous infusion. At 48 h after two 5-day courses, median lymphocyte levels (x 10(9)/l) were 6.0 (387% increase) in the subcutaneous arm (n = 9) and 5.9 (369% increase) in the intravenous arm (n = 8). Liver and renal toxicity were similar in the two groups. One minor response lasting 4 months occurred in 12 renal cancer/melanoma patients receiving subcutaneous treatment and one durable complete remission continuing at 30 months and one minor response lasting 10 months occurred in 6 renal cancer/melanoma patients receiving intravenous treatment. PMID- 1627373 TI - Prognostic value of epidermal growth factor receptor in a series of 303 breast cancers. AB - 125I-EGF (epidermal growth factor) binding assay was used in tumoral specimens concerning 303 clinical T1-T2, N0-N1 breast carcinoma diagnosed between May 1987 and October 1989. Binding assay for epidermal growth factor receptor (EGFR) was performed using single saturating concentration of 125I-EGF incubated with membrane preparations in the presence or absence of unlabelled EGF. A median value of 3 fmol EGF binding capacity per mg of membrane was obtained and then selected as the threshold value to define positive and negative EGFR tumour samples. According to this definition, 50.8% of the samples were EGFR positive. We noted an inverse relationship between the expression of EGFR and that of oestrogen receptor, and a decreased EGFR expression with tumour differentiation. With a rather short median follow-up (16 months), the multivariate analysis shows that progesterone receptor appears as the only powerful predictor of disease-free survival (P = 0.002), taking into account that 70% of the patients received an adjuvant medical treatment. PMID- 1627374 TI - Inter-observer and intra-observer variability of mammogram interpretation: a field study. AB - To evaluate the performance of radiologists in mammographic mass screening, seven radiologists read blindly the mammograms of 45 women (two views for each breast). The films included 12 normal, 24 benign disease and 9 cancers. The readings were repeated after 2 years. As expected, variability was higher among radiologists than between the two readings of the same radiologist, but general reproducibility was moderate. Kappa values for a positive/negative classification were 0.45 at the first and 0.44 at the second reading (inter-observer comparisons). For the intra-observer comparisons, Kappa values ranged from 0.35 to 0.67 (mean 0.56). Generally, accuracy was low partly due to the difficulty of the cases. A slight increase in sensitivity was observed at the second reading. The level of agreement is a good indicator of accuracy. Proper training and standardization of criteria are essential before mass breast screening is implemented. PMID- 1627375 TI - Surgical treatment for chest wall recurrence of breast cancer. AB - From 1977 to 1987, 23 patients with isolated chest wall recurrence, excluding sternal metastasis, from breast cancer underwent full thickness chest wall resection. The 5-year survival rate after chest wall resection was 48% but the 5 year relapse-free survival rate was 26%. Mediastinal metastasis was proved histologically at the time of chest wall resection in 7 patients, and survival period with mediastinal involvement was significantly (P less than 0.01) shorter than that with no mediastinal involvement (n = 16). In 17 patients with a long disease-free interval (DFI greater than or equal to 24 months), survival was longer than in 6 patients with a short DFI (less than 24 months). For the selected patients without mediastinal involvement and long DFI, surgical treatment for chest wall recurrence of breast cancer should play a significant role in improving the quality of life, and even in prolonging the survival rate. PMID- 1627376 TI - Determinants of the psycho-social outcome after operation for breast cancer. Results of a prospective comparative interview study following mastectomy and breast conservation. AB - In a prospective interview study, designed to compare the psycho-social outcome after a breast-conserving vs. a mastectomy operation, we analysed possible predictors of the psycho-social adjustment. 99 women with breast cancer histopathological TNM stages I and II were consecutively admitted to the study. Half-structured interviews, based on the Social Adjustment Scale and a scale by P. Maguire, were performed 4 and 13 months after the operation. Living together with the spouse seems to protect women from developing psycho-social problems postoperatively. Women who were gainfully employed or who were given radiotherapy had a higher risk of poor adjustment after 4 months. At 13 months, the scorings indicate that radiotherapy has a reassuring effect. Type of surgery was controlled for in the analysis and showed that, of the risk factors studied, the most consistent trend for an overall better outcome was in the breast-conserved group except for sexual disturbances. PMID- 1627377 TI - Breast carcinoma and skeletal formation. AB - We have studied skeletal structure in 67 women with breast carcinoma and in 59 women without breast carcinoma, looking for differences of development that might be correlated with hormonal, metabolic or genetic abnormalities. We have measured the lengths of the limbs and of their segments (upper arm, forearm, thigh, leg), of the bisacromial and bitrochanteric transverse diameters and total height and height divided into the parts from vertex to pubis and from pubis to the ground. The analysis showed statistically significant coefficients of regression with presence of mammary carcinoma for height (0.0904262, S.D. 0.0461), length of thigh (0.12989, S.D. 0.03981) and length of lower leg (-0.68475, S.D. 0.1390). This skeletal type might be the expression of a genetic condition that is associated with the existence of mechanisms that permit development of mammary cancer. PMID- 1627378 TI - A phase I study of local treatment of liver metastases with recombinant tumour necrosis factor. AB - 15 patients with therapy-resistant liver metastases were treated in a phase I study with recombinant tumour necrosis factor (rTNF). rTNF was injected into a liver metastasis by ultrasound guidance, using a 50 micrograms escalating dose schedule (3 patients/dosage) ranging from 100 to 350 micrograms per injection. Influenza-like symptoms such as fever, chills, nausea and vomiting were the main clinical side-effects. 2 patients experienced transient hypotension, probably due to concomitant use of morphine. Other toxicities, as reported after systemic use of rTNF, such as decrease in leucocytes and platelet counts, renal or liver toxicity were not observed. No difference was seen in subpopulations of lymphocytes (CD3+, CD4+, CD8+, CD16+ and CD19+) prior to and after rTNF injection. In 8 patients stable disease occurred in rTNF-treated metastases. The maximal dose used by this route of administration is 350 micrograms per injection. Based on these observations we conclude that the toxicity of rTNF injected into liver metastases by sonographic control is transient and mild. The results suggest that intratumoral administration of rTNF might play a role in local tumour control. PMID- 1627379 TI - Prediction of survival by thymidine labelling index in patients with resistant ovarian carcinoma. AB - The relationship between tumour proliferative activity, evaluated by thymidine labelling index (TLI), clinicopathological variables and clinical outcome, was analysed in a series of 64 chemotherapy-resistant, ovarian cancer patients. The median TLI of 4.6% (range 0.01-45.7) was used as the cut-off to discriminate rapidly from slowly proliferating tumours. Univariate analyses showed a significant advantage in survival for patients with TLI less than or equal to 4.6 (P = 0.0004), ECOG performance status less than or equal to 1 (P = 0.0001) and residual disease after primary surgery less than or equal to 2 cm (P = 0.019). Multivariate analysis demonstrated that performance status was the only independent prognostic variable, although TLI was the last covariate removed from the Cox's regression model. PMID- 1627380 TI - Effect of the dosing interval on myelotoxicity and survival in mice treated by cytarabine. AB - Many antineoplastic drugs are cell-cycle-phase-specific. These drugs are often highly toxic to the host, as they have the potential to impair replication, not only in the cancer cells, but also in the normal tissues. Using mathematical models it has been shown how selectivity of these drugs can be increased by exploiting the relatively large variability in cell-cycle parameters of the neoplasia. These models predict that toxicity to the host of cell-cycle-phase specific drugs can be minimised if the dosing interval is an integer multiple of the average intermitotic interval of the susceptible host cells. Experimental evidence supporting this prediction is presented in this work. Our results show that a constant duration of the dosing interval yields higher survival rates in mice treated by cytarabine, as compared with random dosing intervals. Minimal myelotoxicity is exerted when the dosing interval is an exact multiple of the inter-mitotic time of bone marrow stem cells and erythroid progenitors (i.e. 7 h). Survival is significantly lower in mice treated every 8 h, or its multiple, as compared with that of mice treated at a 7 h or 10 h dosing interval. PMID- 1627381 TI - Stability of K-ras mutations throughout the natural history of human colorectal cancer. AB - We have used a rapid, non-radioactive and sensitive method based on allele specific amplification using the polymerase chain reaction for the identification of K-ras mutations in archival tissues of colorectal carcinomas. Our purpose was to determine whether or not K-ras mutation provides, when present, a tumour marker throughout the natural history of the disease. We have studied 35 patients who developed recurrent cancer. In 71% of these patients a ras mutation in codons 12 or 13 was observed in the primary tumour. For each of these cases an identical ras mutation was found in the DNA from the local or distant recurrence. In the 29% of cases where no ras mutation was observed in the primary tumour, no newly acquired ras mutation appeared in the recurrent tumour. The time interval between primary tumours and recurrences varied from 3 to 60 months. Our results indicate that K-ras mutation provides a stable tumour marker throughout the natural history of colorectal cancer. PMID- 1627382 TI - beta-Carotene-mediated inhibition of a DNA adduct induced by 7,12 dimethylbenz(a)anthracene and 7-hydroxymethyl-12-methylbenz(a)anthracene in mouse mammary gland in vitro. AB - The influence of beta-carotene on the formation of DNA-adducts induced by 7,12 dimethylbenz(a)anthracene (DMBA) and 7-hydroxymethyl-12-methylbenz(a)anthracene (7-OHM-12-MBA) during transformation of mouse mammary cells in organ culture was analysed. Treatment with beta-carotene (10(-8)-10(-5) mol/l) caused inhibition (48.8-94.4%) of an adduct (VI), which was detectable in DNA samples from DMBA treated mammary glands. Out of six adducts, derived from further analysis of DNA samples from 7-OHM-12-MBA-treated glands, adduct f eluted in the same fraction as adduct (VI), indicating these adducts were analogous. Likewise, adduct f was also inhibited by beta-carotene. Boronate chromatographic analysis revealed this particular adduct was a syn-dihydrodiol epoxide product. Adduct inhibition was detectable both at the start and after DMBA treatment. alpha-Tocopherol and canthaxanthin were ineffective in inhibiting adducts. It is reasonable to conclude that beta-carotene-mediated modification of adducts is associated with the inhibition of a syn-adduct, which is derived from further metabolism of a 7 OHM-12-MBA intermediate. PMID- 1627383 TI - Altered platelet stearic to oleic acid ratio in malignancy. AB - Alteration of lipid metabolism associated with malignant disease is well documented and some studies have suggested a reduced stearic to oleic acid ratio occurs in erythrocytes in cancer patients. In this study, the fatty acid composition was measured in platelets, which are capable of lipid synthesis and have a much shorter lifespan. While demonstrating any malignancy related change in the platelet stearic to oleic acid ratio the study aimed to assess whether it could be of value as a tumour marker. Patients with active malignancy (n = 46) had a lower ratio of stearic to oleic acid than those with malignant disease in clinical remission [mean (S.D.) 1.08 (0.22) vs. 1.26 (0.30), P less than 0.01], and 22 healthy controls [1.29 (0.24), P less than 0.001]. However in a group of 17 patients with chronic, non-malignant diseases the ratio was also lower than in normal controls and similar to that seen in the active malignancy group [0.97 (0.29)]. Thus while a reduction in platelet stearic to oleic acid ratio was found in active malignancy, it is not specific to neoplastic disease. PMID- 1627384 TI - Levamisole plus 5-fluorouracil inhibits the growth of human colorectal xenografts in nude mice. AB - Fragments of human colorectal adenocarcinomas were inserted under the renal capsule of nude mice. The growth of these tumour grafts was significantly inhibited by the combination of 5-fluorouracil (5-FU) and levamisole. An alternating regimen of levamisole 2.5 mg/kg and 5-FU 20 mg/kg decreased the size of tumour implants by 33-59% and/or increased the number of macroscopically disappeared fragments in the combined group compared with ineffective monotherapy with saline, levamisole or 5-FU. This model could be valuable for investigating the mechanism of action of levamisole and to evaluate the effects of this adjuvant therapy in other oncological settings. PMID- 1627385 TI - The influence of hyperthermia on the uptake of cisplatin in the rat cervical spinal cord. AB - The influence of local hyperthermia on the uptake of cisplatin in the rat cervical spinal cord was investigated. After single intraperitoneal or intravenous injection of cisplatin (5 mg/kg body weight), the spinal cord region cervical 5-thoracic 2 was heated for 60 min at mean (S.D.) 41.2 (0.4) degrees C or 40 min 42.4 (0.3) degrees C using a 434 MHz microwave heating device. One day after treatment with either hyperthermia alone, cisplatin alone or the combination, none of the animals expressed neurological symptoms. The spinal cord was dissected and platinum levels were measured by flameless atomic absorption spectroscopy. No difference was found in uptake of platinum in the spinal cord between control- and heat treated animals. In a second series of experiments, the spinal cord was heated for 30-60 min. during a 2 h infusion of cisplatin. One day after treatment at 42.3 degrees C for 60 min, neither motor nor sensory functions were affected and platinum levels did not differ significantly between control and treated animals. Also, platinum levels measured in the spinal cord immediately after cisplatin infusion were not influenced by heat treatment at 42.1 or 43.0 degrees C for 30 min. However, after a heat dose of 60 min 43 degrees C, cisplatin uptake was significantly increased (P less than 0.001) by a factor of 2.8 (1.3). The data demonstrate that mild hyperthermia has no effect on the uptake of cisplatin in the spinal cord, while an injurious heat dose leads to a significant increase in cisplatin uptake. The present findings indicate that, in case of treatment of tumours of the central nervous system with hyperthermia and cisplatin, a treatment which might be toxic for the tumour is well tolerated by the normal nervous tissue. PMID- 1627386 TI - Pregnancy-related factors and risk of breast cancer in a prospective study of 29,981 Norwegian women. AB - It has been suggested that pregnancy is associated with a short-term increased risk of breast cancer followed by a life-long protection. We studied 340 incident cases of breast cancer in relation to parity, age at first full term birth, and time since last child birth during 14 years follow-up in a prospective cohort of 29,981 Norwegian women. We found no evidence for a transient increase in risk of breast cancer subsequent to pregnancy followed by a reduction in risk of long lasting duration. However, our results indicate that up to an approximate age of 45 years, the nulliparous have a lower breast cancer risk than everparous women. Among parous women, there was an increasingly protective effect on breast cancer risk at a young age (less than 50 years) with increasing number of child births, independent of age at first birth, whereas the protection associated with an early age at first full term pregnancy may increase in importance with increasing age. This finding may reconcile conflicting reports related to these two factors. This study confirms the results of previous investigations suggesting that a "cross-over" in breast cancer incidence between nulliparous and ever-parous women appears to take place some time during the fifth decade of life. PMID- 1627387 TI - Host factors and breast cancer growth characteristics. AB - The rate of growth and spread of breast cancer varies considerably from patient to patient. An observational study was undertaken to identify possible associations between breast cancer growth characteristics and a wide variety of host factors, including demographic, anthropometric, hormonal and dietary variables in 91 patients with breast cancer. Increasing age was associated with favourable growth characteristics, while previous tonsillectomy was associated with adverse growth characteristics. There were no significant associations in anthropometric variables. For postmenopausal women, increasing bioavailability of oestradiol was associated with favourable growth characteristics, while increasing prolactin concentration was associated with adverse growth characteristics. Increasing consumption of sugar, fibre, fruit and vegetables and vitamins was associated with favourable growth characteristics. Consumption of fat (monounsaturated and saturated) was associated with adverse characteristics when adjustment was made for total energy intake. The host environment may play a role in the control of breast cancer growth. In particular, the associations with oestrogen and progesterone receptor status indicate that nutrients may be of value as biological response modifiers in patients having hormonal therapy. This requires further investigation to assess therapeutic potential. PMID- 1627388 TI - A comparison of menstrual cycle profiles of salivary progesterone in British and Thai adolescent girls. AB - Menstrual-cycle profiles of salivary progesterone concentration, obtained by radioimmunoassay of daily samples collected throughout the cycle, were obtained from Thai (n = 232) and British (n = 130) adolescent girls up to 4 years postmenarche. These profiles were graded from 1 to 5 ranging, respectively from concentrations at the detection limit of the assay to profiles generally observed for the mature premenopausal woman. Contingency table analysis of the grade frequencies for Thai-British pairs of girls matched for chronological age and age at menarche (n = 2 x 90) demonstrated that British girls had more mature cycles (22/90) than Thais (11/90) (P less than 0.05) particularly in the first 2 years postmenarche (P less than 0.01). For these matched pairs of girls there was no evidence to support the view that girls with an early age of menarche develop their profiles more quickly following menarche than those with a late age of menarche, as previously reported and which was thought to be important in the development of breast cancer. The findings of this study also suggest that adolescent girls in Britain develop their menstrual cycle profiles of salivary progesterone more quickly than their Thai counterparts and this may be of value in formulating hypotheses regarding any role that ovarian progesterone secretion may have on subsequent breast cancer risk. PMID- 1627390 TI - Cutaneous melanoma and sunburns in childhood in a southern European population. AB - A population-based case-control study of 260 patients (74 males and 186 females, mean age = 56) with cutaneous malignant melanoma and 416 controls (211 males and 205 females, mean age = 55) was conducted in Turin, north-west Italy, to examine the relation between timing of sunburns and sun exposure and melanoma risk within a southern European population, which is still relatively little investigated. Particularly elevated risk was associated with history of sunburns in childhood [odds ratio 5.9; 95% confidence interval (CI) 3.6-9.5], and such risk elevation persisted after allowance for other major melanoma risk covariates. Conversely, risk increase from history of severe sunburns lifelong was lower (odds ratio = 1.7; 95% CI: 1.1-2.4) and was eliminated by allowance for type of skin reaction to sun exposure and history of sunburns in childhood. A significant increase in the risk of cutaneous malignant melanoma was also associated with number of weeks spent on holiday at the beach not only as an adult, but also as a child. PMID- 1627389 TI - Attributable risks for oesophageal cancer in northern Italy. AB - The population attributable risk for oesophageal cancer in relation to cigarette smoking, elevated alcohol use and low beta-carotene intake has been estimated with 300 cases and 1203 controls in Greater Milan. In males 71% of oesophageal cancers were attributable to smoking, 45% to elevated alcohol use and 40% to low beta-carotene consumption. The corresponding figures were 32%, 10% and 29% in females and 61%, 39% and 38% in total. The overall estimate, including the joint effect of the three factors, was 90% in males, 58% in females and 83% in total. The discrepancies between the sums are due to the assumption of a multiplicative model and to the great percentage of oesophageal cancers attributable to each single factor. Cigarette smoking is the major known cause of oesophageal cancer and the three factors account for practically all the difference between male and female mortality rates. Elimination of smoking, reduction of alcohol consumption and enrichment of diet with fruit and vegetables would make oesophageal cancer a rare disease in Italians of both sexes. PMID- 1627391 TI - Oral contraceptives and breast cancer risk in Denmark. AB - To evaluate the influence of oral contraceptives (OCs) on breast cancer risk, a population-based case-control study was conducted in Denmark. The study population included women aged less than 40 years (203 cases, diagnosed between 1 March 1983 and 31 August 1984, and 212 controls) and women aged 40-59 years (856 cases, diagnosed between 1 March 1983 and 29 February 1984, and 779 controls). Cases were identified from the nationwide clinical trial of the Danish Breast Co operative Group and the Danish Cancer Registry. The control groups were age stratified random samples of the general female population. Data on OC use and breast cancer risk factors were collected by self-administered questionnaires. In both age groups, no significant association was detected between breast cancer risk and duration, age at start, latency or recency of OC use. However, the data provided some limited support that OCs containing 50 micrograms or more oestrogen may be more harmful than pills with a lower oestrogen dose. PMID- 1627392 TI - Diethylstilboestrol: I, Pharmacology, Toxicology and carcinogenicity in humans. AB - Diethylstilboestrol is still used as an adjunct palliative treatment in certain patients with breast and prostate cancer. Its pharmacological, toxicological and carcinogenic properties are reviewed. In addition to the usual untoward effects following subacute or chronic administration of oestrogens, treatment with diethylstilboestrol has been associated with serious cardiovascular sequelae. Most characteristic are, however, the carcinogenic properties of this drug. Many epidemiological data provide evidence that prenatal exposure to diethylstilboestrol is causally associated with vaginal and cervical clear-cell adenocarcinomas, a very rare type of cancer in the unexposed female population. The intrauterine exposure of males leads to an increased risk of testicular cancer, although the data are less conclusive in this respect. There is some evidence that administration of diethylstilboestrol in large doses to adult women during pregnancy increases the risk of subsequent breast cancer and it probably increases the incidence of endometrial carcinoma, as has been shown with other similar oestrogens given chronically for menopausal symptoms. PMID- 1627393 TI - New approaches in cancer pharmacology: drug design and development. Report of a European School of Oncology Task Force. PMID- 1627394 TI - Cell kinetic alterations during epidermal carcinogenesis. EACR--Muhlbock Memorial Lecture, 1991. PMID- 1627396 TI - Minimal guidelines for the monitoring of early clinical trials (phase I-II) in Europe under CRC/EORTC/NCI joint agreement. PMID- 1627395 TI - Trends of cancer mortality in Europe, 1955-1989: IV, Urinary tract, eye, brain and nerves, and thyroid. PMID- 1627397 TI - Problems associated with the study of cytokines in patients with leukaemia. PMID- 1627398 TI - Cisplatin-induced sodium and magnesium wastage. PMID- 1627399 TI - Suramin and prostate cancer: the role of hydrocortisone. PMID- 1627400 TI - Comparison of growth fraction with tumour stage and grade in renal cell carcinoma. PMID- 1627401 TI - Early ovarian cancer and the icon trials. PMID- 1627402 TI - Sociocultural habits and urological malignancies in Ibadan, Nigeria. PMID- 1627403 TI - MMAF for advanced gastric cancer. PMID- 1627404 TI - Prolonged thrombocytopenia after procarbazine "overdose". PMID- 1627405 TI - Rare occurrence of amplification of HER-2 (erbB-2/neu) oncogene in ovarian cancer patients. PMID- 1627406 TI - The impact of cytotoxic chemotherapy--perspectives from patients, specialists and nurses. AB - This study, carried out in three European countries, elicited the views and impact of three medical groups involved in patient care. Their views were compared with patients' perspectives of their condition. The main stage of the study was carried out by self-completion questionnaires by 300 patients across Italy, France and the U.K. The views of the medical profession were quantified via 150 hospital specialists, 75 cancer care nurses and 30 general practitioner interviews. Patients' symptoms most frequently seen by the medical profession were nausea, tiredness, loss of hair, vomiting, worrying and lack of appetite. On a scale of 1-4 (1 = not at all; 4 = very much) the frequency of these side effects were rated at 2.8 or over. Intensity of concern was highest for nausea and vomiting. These two symptoms was most frequently highlighted as one of the three highest concerns respectively for 74% and 54% of specialists, 64% and 60% of nurses and 50% of general practitioners. Patients on average reported a lower frequency of major symptoms. Most frequent were loss of hair, tiredness, lack of energy, nausea and decreased sexual interest. In terms of the impact of these problems, tiredness, nausea and loss of hair were the most frequently mentioned. Vomiting bothered them more than the frequency would suggest. 1 in 10 patients claim to have delayed their treatment because of previous experiences of side effects. The main impact on patient's quality of life related to the aspects of worrying and the effects on the family. In terms of communication, both the medical profession and the patients felt that patients were well informed about the disease and treatment. However, differences emerged between what patients claim to have been told about the disease and its treatment and what nurses and doctors claim to have said. PMID- 1627407 TI - Behavioural interventions and psychological aspects of care during chemotherapy. AB - Numerous studies have reported the deleterious impact that the side effects of cytotoxic chemotherapy can exert on the quality of life in patients with cancer. Nausea and vomiting consistently feature as the most distressing aspects of cancer therapy. Uncontrolled emesis can cause patients to abandon treatment and the poor public image of chemotherapy may lead others to refuse treatment altogether. Anticipatory nausea and vomiting can also develop in patients and this may persist for many years after successful completion of treatment. There are several behavioural interventions that are effective in ameliorating or preventing these unpleasant side effects. Consequently, psychological support should be provided as an integral part of good patient management, alongside appropriate antiemetic and anxiolytic drugs. As we can identify the characteristics of those patients more at risk from severe emesis and the development of anticipatory problems, there are good arguments for the most effective drug therapy (rather than the cheapest) being given to them prophylactically, together with relaxation techniques. PMID- 1627408 TI - Medical costs of osteoporosis. AB - Global healthcare expenditure has risen at an alarming rate over the past thirty years and the situation is most pronounced in the USA, which now spends 12% of its gross domestic product on healthcare. The greatest component of this expenditure is accounted for by the costs of hospitalisation, and is also particularly centred on the elderly sector of the population - a group that, relative to other sections of the population, will expand over the next thirty years. Osteoporosis, a chronic, disabling disorder, predominantly affects the elderly. Growth in the recognition and level of intervention in osteoporosis, when viewed alongside the increase in the elderly population, emphasises the need to examine the costs of osteoporosis against the already burgeoning healthcare bill. A detailed study in the USA in 1986 assessed the direct medical costs of osteoporosis in women over the age of 45; analysis included the costs of hospitalisation, nursing home care and outpatient services. The results of this survey revealed a figure for total direct costs of $5.15 billion, with hospital and nursing home care being the greatest contributors. A subsequent analysis of data for 1989 has shown expenditure to have risen to over $6 billion. This form of economic assessment of direct medical costs, based on discharge surveys and audit data, is likely to be reasonably accurate for osteoporosis-related hip and wrist fractures, which will generally present to hospitals, but less so for vertebral fractures, which have a varied clinical presentation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627409 TI - The success and failure of the adaptive response to functional load-bearing in averting bone fracture. AB - The skeleton's ability to sustain loads without fracture requires bone mass and architecture to be appropriate for the loading involved. Load-bearing is the only functional influence which requires any particular bone architecture, and functionally-engendered strains provide the only feedback relevant to both the bone's loading and its structural suitability. The specific strain-related objectives of the mechanically-related modelling/remodelling response responsible for matching structure to load-bearing have not been adequately defined but they appear to be different for cortical and cancellous bone. Static loads have no effect on modelling/remodelling activity whereas the effects of dynamic loading can be profound. The osteogenic effect of loading appears to be greatest when the strains and strain rates are high and the strain distributions unusual. This raises the possibility of continued load-bearing which only involves restricted activity patterns being interpreted by the bones' cell population as relative disuse. The osteogenic stimulus of each loading configuration appears to saturate after a few daily loading cycles. Since loading produces a local effect on modelling/remodelling, exercise regimens whose objective is to preserve or increase bone mass must be designed in relation to load-bearing at each skeletal location. Through their independent effects on bone cells nutritional and hormonal factors can enable, enhance, limit, or frustrate full expression of the adaptive response to loading. However, such systemic factors cannot engender, or successfully imitate, the cumulative local osteo-regulatory effects which loading engenders. This explains the absence of any natural systemic substances capable of engendering a sustained, structurally appropriate increase in bone mass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627410 TI - The natural history of vertebral osteoporosis. Is low bone mass an epiphenomenon? AB - Osteoporotic bone fragility is due not only to decreased bone mass but to inadequate repair of fatigue damage and to trabecular disconnection. The precise roles and relative contributions of these three factors are not known for osteoporosis in general, and certainly not in any individual case. However, it is known that reduced physical activity causes bone loss. It is a virtual certainty, therefore, that, to the extent that the fracture produces disability, osteoporotics lose bone after they first experience a fracture, whatever its antecedent causes. In that sense, some of the bone loss we find in our patients is indeed an epiphenomenon. However, this is not to suggest that reduced bone mass is unimportant. Quite the contrary: prospective studies have clearly established that reduction in bone mass does increase risk of fracture, and hence, when it is consequent upon a fracture, it aggravates the patient's condition. In this way a vicious circle may develop: the pain and fear that follow fracture lead to decreased activity, which leads to bone loss, which can only increase the fragility, and hence predispose to further fracturing, even in cases in which the initial fragility may not have been due to low bone mass. But low bone mass, with its proper fragility, may not be inevitable. That is why pain control and a comprehensive programme of rehabilitation are critically important in the early management of patients with symptomatic vertebral fractures. PMID- 1627411 TI - The clinical consequences of vertebral compression fracture. AB - Vertebral compression fractures (VCFs) may be defined radiographically or as a clinical event. The prevalence of these fractures in women aged 50 and over has been estimated at 26% when defined as a reduction in vertebral height greater than 15%. Retrospective reviews of case records have shown a clinical detection rate of VCF in white women of 153/100,000 person years. Of these clinically detected VCFs, 84% were associated with pain. VCF may be defined as a clinical event characterised by loss of height and acute pain. The pain of acute fracture usually lasts 4 to 6 weeks with intense pain at the site of fracture. Chronic pain may also occur in patients with multiple compression fractures, height loss and low bone density but is probably due to structural changes or osteoarthritis. Radiographic VCF may not be symptomatic. The greater the deformity, the greater the likelihood of pain and disability. As height is lost, patients experience discomfort from the rib cage pressing downward on the pelvis. Patients develop a thoracic kyphosis, a lumbar lordosis, and a protuberant abdomen with prominent horizontal skinfold creases. The reduced thoracic space may result in decreased exercise tolerance and reduced abdominal space may give rise to early satiety and weight loss. Sleep disorders may also occur. Patients lose self esteem. Self care may become difficult. They are often depressed. They become fearful of further fracture. They have distorted body image and poor health perception. Patients with one vertebral fracture are at increased risk of peripheral fracture and further vertebral fracture. The aims of acute management are to reduce symptoms and mobilise the patient as quickly as possible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627412 TI - The radiological assessment of vertebral osteoporosis. AB - The traditional skeletal X-ray is of little help in quantifying osteopenia in the spine, and indirect criteria, such as increased lucency, loss of horizontal trabeculae and reduction in end-plate thickness with relatively increased opaqueness, can be misleading. However, the clinical expression of osteoporosis is fracture, which can be identified by radiography. Any reduction in the anterior, middle, or total height of the vertebral body should be classified as vertebral fracture. In mild cases, such fractures are not easily detectable, particularly when previous radiographs are not available for comparison. Thus several objective methods for fracture identification have been developed. Most of these methods are based on the ratio between posterior and anterior or middle height (wedge or biconcave deformity, respectively) and on the ratio between posterior height of adjacent vertebrae or with a single vertebral reference (T4). Some of these indices are referred to normal ranges in order to take into account intervertebral and interindividual variability. In 36 women with postmenopausal osteoporosis we have compared the lateral radiographs of lumbar and thoracic spine to similar X-ray pictures taken by chance at least five years before menopause. By defining a fracture as any decrease in vertical height above 1 mm, we found 77 deforming events in 29 out of 36 patients. We then applied some of the methods to identify objectively fractures in our postmenopausal radiographs: the sensitivity of the various systems ranged from 50 to 100%; however there was a large overlap between false positives and false negatives and the methods with the highest sensitivity lack specificity and vice versa. PMID- 1627413 TI - Management of high turnover osteoporosis with calcitonin. AB - Osteoporosis, associated with a high turnover of bone and acute bone loss, occurs in a number of clinical models, such as following prolonged steroid therapy, extremity and spinal immobilisation, and often is associated with fracture. Confinement to bed and subsequent hypodynamism relating to the pain following a vertebral fracture may activate the process of high bone turnover and acute bone loss. In postmenopausal women, the acute bone loss resulting from such clinical pictures may be superimposed on to the natural course of bone loss occurring in many postmenopausal women. Salmon calcitonin, a potent inhibitor of osteoclast activity, has been shown to prevent bone loss in all clinical models of acute bone loss due to increased bone turnover and osteoclastic resorption. In addition, salmon calcitonin has a potent analgesic effect, thereby causing a reduction in bone pain and improvement in functional capacity. For these reasons, calcitonin remains a first-line therapy in bone loss related to a hyper resorptive state. PMID- 1627415 TI - NIH Consensus Development Conference on the Treatment of Early-Stage Breast Cancer. Bethesda, Maryland, June 18-21, 1990. PMID- 1627414 TI - Implications of architecture for the pathogenesis and prevention of vertebral fracture. AB - Rapid loss of cancellous bone after menopause occurs by a mechanism that removes some structural elements completely, leaving those that remain more widely separated and less well connected. Slow loss of cancellous bone continues by a mechanism that reduces the thickness of the structural elements that survive the initial phase of rapid loss. Both processes have advanced further in patients with vertebral compression fracture due to osteoporosis, than in healthy subjects of similar age; whether this is because they began sooner, proceeded more rapidly or continued for longer is unknown. This overall concept, first developed about ten years ago, has now been confirmed by a variety of different methods including node-strut analysis, star volume and the change in curvature with profile dilation. Because part of the architectural contribution to compressive strength is captured by non-invasive densitometric methods, and the contribution of cortical bone to compressive strength is significant, it has been difficult to demonstrate an independent architectural component of bone fragility by in vitro comparison of structural measurements with biomechanical testing. Nevertheless, three independent clinical studies, comparing subjects with and without vertebral fracture, have each strongly suggested an independent architectural contribution to fracture risk. Complete removal of structural elements is initiated by focal perforation of trabecular plates, but the mechanism of perforation remains controversial.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627416 TI - Consensus statement: treatment of early-stage breast cancer. National Institutes of Health Consensus Development Panel. PMID- 1627417 TI - Systemic therapy in node-negative patients: updated findings from NSABP clinical trials. National Surgical Adjuvant Breast and Bowel Project. AB - This report updates findings from two National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trials conducted to evaluate the worth of systemic therapy for the treatment of node-negative breast cancer patients. In trial B-13, 737 women with estrogen receptor (ER)-negative tumors treated by sequential methotrexate and fluorouracil (MTX----5-FU) followed by leucovorin were compared with a control group treated by surgery alone. Findings for all patients through 5 years of follow-up indicate a 27% reduction in treatment failure as a result of MTX----5-FU (76% vs 67%). While patients 49 years old or less and 50 years old or more benefited significantly from MTX----5-FU, the effect on disease-free survival (DFS) was greatest in those 50 years or older, where a 50% reduction in treatment failure occurred (86% vs 72%). A 69% reduction in mortality resulting from MTX----5-FU was observed in the older group (95% vs 84%). Trial B-14 compared placebo with tamoxifen (TMX) in 2844 patients with ER-positive tumors. As originally reported, findings through 5 years of follow-up indicate a significant reduction (36%) in treatment failure as a result of the TMX (82% vs 72%). Improvement in DFS was highly significant in both age groups. In patients 49 years old or younger, there was a 44% reduction in DFS (81% vs 66%) and, in those 50 years old or more, a 31% reduction (82% vs 74%). A Cox proportional hazards model failed to indicate a benefit from MTX----5-FU and TMX in all patient subgroups. Both therapies reduced local-regional and distant recurrence, as well as breast tumor recurrence following lumpectomy. Updated findings from trials B-13 and B-14 continue to support our conclusions that (a) no subgroups of node-negative patients that we examined have such a good outcome as to preclude the use of effective systemic therapy in their treatment and (b) despite the benefits observed from MTX----5-FU and TMX, no subgroup of patients was so affected as to preclude use of a particular subgroup in assessing other therapy regimens in additional clinical trials. The identification and evaluation of markers to determine which patients should receive systemic therapy are of the highest priority. At present, however, the use of markers for therapeutic decision making regarding individual patients is tenuous. PMID- 1627418 TI - The Christie Hospital adjuvant tamoxifen trial. AB - A clinical trial was carried out at The Christie Hospital, Manchester, England, between November 1976 and June 1982. Following surgery, patients with clinical stage T1-T3a, N1-N2b, M0 tumors were randomly allocated in the following way: premenopausal women to either tamoxifen 20 mg/day for 1 year or to an irradiation induced menopause; postmenopausal women to either tamoxifen for 1 year or no further treatment (controls). In the node-negative subgroup, an analysis at a median follow-up of 10 years shows no statistically significant difference in overall or disease-free survival between tamoxifen-treated patients and irradiation-induced menopause and control patients. Side effects were few, and compliance was excellent. There was no significant increase of second primary tumors in target endocrine organs in the tamoxifen-treated patients. For the whole series of 961 patients, a log-rank analysis of events, allowing for node status, still shows a statistically significant benefit for tamoxifen-treated patients (P = .04). PMID- 1627419 TI - Use of a physician-directed questionnaire to define a consensus about management of breast cancer: implications for assessing costs and benefits of treatment. AB - The present study was designed to assess the preferred methods of treatment of early breast cancer by United States oncologists, to define the impact of published clinical trials on their practice, and to define questions related to clinical decision making that should be subjected to further research. A questionnaire was mailed to 405 oncologists of all three disciplines (medical, radiation, and surgical oncology) and to 60 oncology nurses who practice in the United States. The questionnaire included clinical scenarios of: (a) a patient with primary breast cancer; (b) a premenopausal woman with node-negative breast cancer; and (c) a postmenopausal woman with estrogen receptor (ER)-negative, node positive breast cancer. Respondents were asked to describe their preferred management for each scenario. Our study demonstrates a consensus that modified radical mastectomy, or partial mastectomy plus radiation therapy, should be offered as equal options to selected patients with primary breast cancer; this consensus is supported by results of clinical trials. We also found agreement that adjuvant chemotherapy should be offered to premenopausal women with node negative, ER-negative breast cancer. There was a similar consensus in favor of adjuvant chemotherapy for postmenopausal patients with ER-negative, node-positive breast cancer, despite the absence of improvement in overall survival in large, mature, controlled randomized trials (and in a meta-analysis). We suggest that further research be undertaken into factors that influence decision making by oncologists when they consider the administration of adjuvant chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627420 TI - A model of chemotherapy in node-negative breast cancer. AB - Should all women with node-negative breast cancer receive chemotherapy? Acceptance of such a broad recommendation has been controversial due to the relatively good prognosis of these women and the lack of evidence of an improvement from chemotherapy in overall survival. We studied the question with a decision analytic model, which simulates a clinical trial of a large number of women over several decades, to calculate quality-adjusted life expectancy and the cost-effectiveness of chemotherapy in 45-year-old and 60-year-old women. The model considered a variety of scenarios about the long-term benefits of chemotherapy. The initial analysis found a lifetime benefit of 4 to 5 quality months (range, 2 to 14 months) at a cost of $15,400 to $18,800 per quality year (range, $5,100 to $56,800). If a risk-stratification protocol could identify a low-risk group, then benefit drops to about 1 quality month at a cost of $65,000 to $90,000 per year. For the average woman, chemotherapy increases the quality adjusted life expectancy by a substantial amount at a generally acceptable cost. However, given the uncertainty of the duration of benefit and current potential for risk-stratification, a broad recommendation for chemotherapy is inappropriate. PMID- 1627421 TI - Randomized clinical trial to assess the value of breast-conserving therapy in stage I and II breast cancer, EORTC 10801 trial. AB - In a prospective randomized clinical trial conducted by the European Organization for Research and Treatment of Cancer (EORTC), mastectomy was compared with breast conserving therapy in 903 stage I and stage II breast cancer patients entering the study between 1980 and 1986. The main participating centers were: Guy's Hospital, London; The Netherlands Cancer Institute, Amsterdam; University Hospital, Leuven; Radiotherapy Institute, Rotterdam; Breast Unit, Tijgerberg, S.A. The data were collected in the EORTC Data Center, Brussels. Treatment in the study arm consisted of lumpectomy, axillary clearance, and radiotherapy to the breast (50 Gy external irradiation in 5 weeks followed by boost with iridium implant of 25 Gy). Important in this study is the large number of TNM stage II patients (755). Most patients were stage II because of the size of the tumor (2-5 cm). The patient and tumor characteristics in the study and control groups were well balanced. So far the survival curves and local recurrence rates are not statistically different for the two study arms. Tumor size was found in univariate analysis to be a significant risk factor for local recurrence in the breast-conserving therapy group but not in the mastectomy group. Results of salvage treatment for local recurrence were not better for the breast-conserving therapy group compared with the mastectomy group. Measurements of quality of life and cosmesis show a clear benefit for the breast-conserving therapy group. PMID- 1627422 TI - Survival and prognostic factors in node-negative breast cancer: results of long term follow-up studies. AB - Seven hundred sixty-seven patients treated at the Memorial Sloan-Kettering Cancer Center from 1964 through 1970 by mastectomy and axillary dissection have now been followed for a median of 18 years. This unusual database consists of a consecutive series of women cared for by physicians specialized in the treatment of breast cancer in one institution. The data suggest that patients with T1, N0, M0 tumors of 1 cm or less may be "cured" by mastectomy and axillary dissection, the estimated proportion of "cured" patients being 89%. The data also suggest that node-negative patients can be placed in categories of risk for recurrence on the basis of primary tumor size. PMID- 1627423 TI - Classical prognostic factors in node-negative breast cancer: the DBCG experience. AB - Classical prognostic factors were analyzed in patients with low-risk primary breast cancer, defined as absence of tumor-positive axillary lymph nodes, tumor size less than or equal to 5 cm in diameter, and no invasion into skin or deep fascia. The primary surgical treatment was total mastectomy and lower axillary dissection. None of the patients received adjuvant therapy. Between 1977 and 1990, 7315 patients entered the study, and at the time of this analysis (January 1, 1990), the median follow-up time is 5 years. In univariate analyses, the following variables were significantly related to recurrence-free survival: age in premenopausal patients; tumor size; number of negative nodes removed; histological grade; and in premenopausal patients, estrogen receptor and progesterone (PgR) status. In multivariate analyses, age in premenopausal patients was the most important factor, followed by tumor size and histological grade, whereas PgR status in premenopausal patients was just of borderline significance. These variables should be included in multivariate analyses testing the value of more recently introduced prognostic factors. PMID- 1627424 TI - Prognostic potential of DNA flow cytometry measurements in node-negative breast cancer patients: preliminary analysis of an intergroup study (INT 0076). AB - An ancillary study (INT 0076) to the Intergroup clinical trial of node-negative breast cancer patients (INT 0011) was performed to retrospectively evaluate DNA flow cytometry measurements of ploidy (DNA content) and proliferative capacity (S phase fraction) for their ability to predict time to recurrence. Of the 915 patients eligible for the clinical trial, 788 were registered for the ancillary flow cytometry study (INT 0076). Four hundred and three of these patients [estrogen receptor (ER)-positive, tumor size less than 3 cm] had been registered to the observation arm of the clinical trial and 385 (ER-negative and/or tumor size greater than or equal to 3 cm) had been randomly assigned to adjuvant chemotherapy (cyclophosphamide, methotrexate, fluorouracil, and prednisone for six cycles) or to observation. Paraffin blocks from 95% (748 of 788) of these patients were obtained, 712 of which had sufficient cancer tissue to be evaluable for the flow cytometric assay. DNA ploidy status (DNA diploid vs DNA aneuploid) was evaluable for 565 (79%) specimens, 64% of which were aneuploid. Proliferative capacity was estimated by the percentage of cells having an S-phase DNA content, using a trapezoidal modeling algorithm(s) as previously described. The median S phase value for the entire group (both registered and randomly assigned patients) was 6.97%, which defined the cutoff for interpretation of high or low S-phase values. With a median follow-up time of 4.55 years, S-phase fraction, but not ploidy status, is a significant predictor for time to recurrence in both the randomly assigned and the untreated population (observed registered group and observed randomly assigned group).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627425 TI - Treatment decisions in axillary node-negative breast cancer patients. AB - Treatment decisions must be made on 9000 axillary node-negative breast cancer patients each month in the United States. Which of these patients will benefit from adjuvant therapy is a major question. Valid methods are needed to distinguish those patients who are "cured" from those who will suffer a cancer recurrence. A complex network of prognostic variables enters into the treatment decision, together with a risk-versus-benefit assessment. We are using a neural network-based form of artificial intelligence that, once "trained" with data representing an event and its outcome, can identify subsets of patients with low recurrence risks. Larger data sets are being evaluated with the hope of introducing the neural-network technique to routine clinical practice. PMID- 1627426 TI - Epidermal growth factor receptor and other oncogenes as prognostic markers. AB - Analysis of epidermal growth factor receptor (EGFr) and estrogen receptor (ER) was performed on tumor samples from 231 patients with operable breast cancer followed for up to 6 years after surgery. The median duration of follow-up in patients still alive at the time of analysis was 45 months. Thirty-five percent of patients (82) had tumors greater than 10 fmol/mg of 125I-EGF binding (EGFr+) and 47% (109) had cystolic ER concentration greater than 5 fmol/mg (ER+), with a marked inverse relationship between EGFr and ER (P less than .00001). EGFr was second only to axillary-node status as a prognostic marker for all patients in terms of both relapse-free and overall survival in univariate analysis (P less than .001, log-rank EGFr + v EGFr-). For patients with histologically negative axillary nodes, EGFr was superior to ER in predicting relapse and survival (P less than .01 and P less than .005, respectively, compared to P less than .1 and P less than .1, log-rank). In a multivariate (Cox model) analysis, only EGFr--out of EGFr, ER, size, and grade--was predictive for either relapse-free or overall survival for patients with node-negative disease (P = .052 and P = .026, respectively). One hundred eighty-seven case patients in the series were assessed for neu expression immunochemically, and 31 were positive. There was a highly significant increased risk of relapse and death in the positive group. In patients with otherwise good prognostic markers (ER+, node-negative, well differentiated tumors), neu expression predicted for significantly worsened overall survival.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627427 TI - Danish randomized trial comparing breast conservation therapy with mastectomy: six years of life-table analysis. Danish Breast Cancer Cooperative Group. AB - The Danish Breast Cancer Cooperative Group (DBCG) conducted a randomized trial comparing breast conservation with mastectomy in patients with invasive mammary carcinoma. From January 1983 to March 1989, the trial accrued a total of 1153 women. Of this number, 905 patients (79%) were randomly assigned to one of the two treatment options, whereas 248 patients (21%) did not accept randomization. Of the randomly assigned patients, 90% received the surgical option to which they had been originally assigned. In the breast conservation arm the tumor was excised with the intention of obtaining free margins determined at gross examination, and radiotherapy was subsequently administered to residual breast tissue. The axilla was dissected in all instances. Patient and tumor characteristics were similar in the two randomization arms. The median follow-up time was 40 months. At 6 years of life-table analysis the probability of recurrence-free survival was 70% in the breast conservation arm against 66% in the mastectomy arm. Survival figures were 79% against 82%, respectively. PMID- 1627428 TI - Results of the National Cancer Institute early breast cancer trial. AB - In 1979, a prospective, randomized trial was begun at the National Cancer Institute comparing lumpectomy, axillary dissection, and radiation therapy (XRT) to modified radical mastectomy for the treatment of invasive breast cancer, clinical stage T1-2, N0-1, M0. Treatment in the radiation arm consisted of full axillary dissection and gross removal of the tumor, followed by 4500 to 5000 cGy to the whole breast and a boost to the tumor bed of 1500 to 2000 cGy. Patients with positive axillary dissections received radiation to the supraclavicular nodes, in addition to cyclophosphamide and doxorubicin. Two hundred thirty-seven patients entered in the trial between 1979 and 1987 are available for analysis, 116 in the mastectomy arm and 121 in the radiation arm. With a median follow-up of 67.7 months, there are no significant differences in 5-year overall survival (85% vs 89%, mastectomy vs radiation) or 5-year disease-free survival (82% vs 72%, mastectomy vs radiation). Patients in the radiation arm had an actuarial in breast recurrence rate of 12% at 5 years and 20% at 8 years. There were no major differences between complication rates in the treatment arms. The results of the study indicate that patients with invasive breast cancer, stage I and II, can be treated with lumpectomy, axillary dissection, and radiation therapy with results comparable to those with modified radical mastectomy. PMID- 1627429 TI - Recurrence in the breast following conservative surgery and radiation therapy for early-stage breast cancer. AB - This report summarizes the experience of the Joint Center for Radiation Therapy (JCRT) in treating patients with clinical stage I and II breast cancer with conservative surgery and radiation therapy. The study population consisted of 1396 patients treated between 1968 and 1985. All patients underwent a gross excision of the tumor and received breast irradiation (with or without nodal irradiation) including a "boost" to bring the primary tumor site to a total dose of at least 60 Gy. The method of treatment evolved over the study-time period. During the interval from 1968 to 1982, patients typically underwent a limited gross excision of the tumor without regard to the microscopic margins of resection. During the period 1983 to 1985, film-screen mammography, inking of specimen margins, and reexcisions for inevaluable or involved margins were more commonly performed. With a median follow-up of 80 months, the 5-year crude rate of failure in the breast (as the first site of failure) was 8% (106/1396) and the crude rate of regional nodal/distant failure (as the first site of failure) was 16% (228/1396). The time-course of failures in the breast was protracted, occurring at a fairly constant rate over the first 7 years after treatment, but still seen beyond that point. Most recurrences in the breast (75%) developed at or near the original tumor site. The most important risk factor for developing a breast recurrence was the presence of an extensive intraductal component in the tumor. The cosmetic results following treatment were excellent or good in the majority of patients (87%) and were most adversely affected by extensive surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627430 TI - Surgical considerations in selecting local therapy. AB - Clinical trials have demonstrated that patients treated with lumpectomy and radiation therapy have long-term survival rates equivalent to those treated with classical forms of mastectomy. Perhaps questions remain about appropriate treatment of the very smallest and the largest of operable breast tumors, but the majority of patients with primary breast cancer can be successfully treated with conservative surgery and radiation. Factors involved in surgical decision making, technical features of lumpectomy, and postoperative treatment are discussed. PMID- 1627431 TI - Radiotherapeutic considerations in the treatment of primary breast cancer. AB - Patients who are candidates for conservative surgery and radiation include those with a primary tumor size of less than 4-5 cm, without evidence of gross multicentricity or diffuse microcalcifications. Patients with an extensive intraductal component may be appropriate candidates, provided that margins of resection are negative. Focally positive margins of resection in patients without an extensive intraductal component are not a contraindication, provided that a boost dose of radiation is employed; young age is also not a contraindication to conservative treatment. The optimal radiotherapy technique includes a total dose to the breast of 4500-5000 cGy with a daily fraction size of less than 250 cGy and a weekly dose of more than 800 cGy. The role of boost treatment in patients with negative margins of resection is currently under investigation. Boost treatment is essential in patients with positive margins. A direct photon-beam field to treat the internal mammary nodes should be avoided, especially in patients receiving chemotherapy. The subset of patients for whom the addition of radiation following an excisional biopsy does not result in a decreased risk of breast cancer recurrence remains to be defined and is currently being evaluated in several prospective randomized trials. The optimal sequencing of adjuvant chemotherapy and primary radiotherapy has not been determined. PMID- 1627432 TI - Lumpectomy for breast cancer: an update of the NSABP experience. National Surgical Adjuvant Breast and Bowel Project. AB - The data in this report continue to indicate, as first noted in 1985, that lumpectomy followed by breast irradiation in all patients, and adjuvant chemotherapy in women with positive nodes, is appropriate therapy for negative- or positive-node patients with tumors 4 cm or less in size, provided that the margins of the resected specimens are free of tumor. The value of irradiation in reducing the incidence of tumor in the ipsilateral breast after lumpectomy continues to be significant in all patients regardless of nodal status, age, or tumor size. A multivariate analysis indicates that, in all patients, three covariates, ie, treatment, tumors with poor histologic type, and tumors with a maximum pathologic size greater than or equal to 2 cm, are significant predictors of breast tumor recurrence following lumpectomy. Of particular significance is the continuing observation that the distant disease-free survival (DDFS) and survival (S) of patients in the three treatment groups (total mastectomy, lumpectomy alone, and lumpectomy followed by breast irradiation) demonstrate no significant difference through 9 years of follow-up, despite the fact that the total mastectomy group (by virtue of breast removal) had no breast tumor recurrence, that lumpectomy patients treated with breast irradiation had a 10% ipsilateral tumor recurrence, and that patients treated by lumpectomy alone demonstrated a 40% recurrence of tumor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627433 TI - Swiss adjuvant trials in women with node-negative breast cancer. OSAKO. AB - Women with node-negative breast cancer have a 30% chance of relapse 5 years after mastectomy. If it is possible to prevent or defer recurrent disease with adjuvant systemic therapy, node-negative patients, with their low tumor burden, should theoretically benefit most from such treatment. In 1974 we started a randomized adjuvant trial in eastern Switzerland, using a subjectively less toxic regimen [chlorambucil, methotrexate, and fluorouracil (LMF)]. Two hundred fifty-four patients were randomly assigned after standardized modified radical mastectomy to observation only or to treatment with oral LMF for 6 months followed by BCG skin scarifications monthly for up to 2 years. While we find no significant statistical difference between the control group and the treated group in terms of relapse-free survival, there is a strong and consistent trend toward prolongation of overall survival within the treated group. PMID- 1627434 TI - Adjuvant CMF for node-negative and estrogen receptor-negative breast cancer patients. AB - From December 1980 to September 1985, a total of 90 eligible patients with stage T1-3a, node-negative, and estrogen receptor-negative (less than or equal to 10 fmol/mg of cytosol protein) tumors were entered into a randomized study to assess the effectiveness of adjuvant intravenous (IV) cyclophosphamide, methotrexate, and fluorouracil (CMF) in a subset of patients at high risk of early disease relapse. High values of [3H]thymidine labeling index were documented in two thirds of 62 assessed specimens from the patient population, and one half of the patients had histologically undifferentiated tumors. Patients were allocated to either local-regional modality alone (control group, 45 women) or to CMF (45 patients) after surgery. A full dose of CMF (600 mg/m2 each of cyclophosphamide and fluorouracil, and 40 mg/m2 of methotrexate) was administered IV on day 1, and then repeated every 3 weeks for a total of 12 treatments. After a median follow up of 80 months, the 7-year results confirmed the superiority of adjuvant CMF compared to local-regional modality alone (relapse-free survival 85% vs 42%, P = .0001; total survival 86% vs 58%, P = .006). A benefit from adjuvant CMF was observed in all subgroups, and the rates of both local-regional and distant failure were decreased. Treatment was fairly well tolerated and devoid of life threatening toxicity. Present results confirm our previous observation concerning the dismal prognosis of node-negative and estrogen receptor-negative breast cancer patients as well as the beneficial effect of adjuvant chemotherapy in this selected subset. PMID- 1627436 TI - A single perioperative adjuvant chemotherapy course for node-negative breast cancer: five-year results of trial V. International Breast Cancer Study Group (formerly Ludwig Group). AB - Twelve hundred seventy-five patients who were defined as having node-negative breast cancer were evaluated in a randomized trial that compared a single cycle of combination chemotherapy started within 36 hours of surgery (848 patients) with no adjuvant treatment (427 patients). The chemotherapy consisted of intravenous cyclophosphamide, methotrexate, and fluorouracil given on days 1 and 8. Leucovorin (given on days 2 and 9) was added to the regimen to decrease severe toxic effects attributed to drug interaction between nitrous oxide used in anesthesia and methotrexate given in the immediate postoperative period. At a median follow-up of 60 months, the 5 year disease-free survival (DFS) percentages (+/- SE) were 74% +/- 2% for the treated group, and 68% +/- 2% for the no adjuvant therapy group. The estimated hazard ratio [95% confidence interval (CI)] was 0.78 (0.63 to 0.96); P = .02, representing a 22% +/- 9% relative reduction in the risk of relapse. The overall survival (OS) difference was not statistically significant with 5-year OS percentages of 88% +/- 1% for the treated group, and 85% +/- 2% for the control group [estimated hazard ratio (95% CI) = 0.85 (0.62 to 1.16); P = .31]. A subgroup analysis by menopausal status and by estrogen receptor (ER) status revealed that the treatment effect was largest among the postmenopausal women with ER-negative tumors. The 5-year DFS percentages were 79% +/- 4% and 56% +/- 7%, and the OS percentages were 91% +/- 3% and 70% +/- 6%, for the treated and control groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627435 TI - West Midlands Oncology Association trial of adjuvant chemotherapy in node negative breast cancer. AB - Between 1976 and 1984, 574 patients with operable breast cancer and histologically negative axillary lymph nodes were randomly assigned after mastectomy to receive either no further treatment or chemotherapy with oral LMF (fluorouracil, 500 mg, methotrexate, 25 mg, and chlorambucil, 10 mg, on day 1; fluorouracil, 500 mg, and chlorambucil, 10 mg, on day 2). There is no overall survival or relapse-free survival benefit at a median follow-up of 10 years and 8 years, respectively. There are significantly more local relapses in the control group (P less than .01), but an excess of distant relapses in the treated group is not statistically significant (P = .24). A positive treatment effect in small tumors (relapse-free survival, odds ratio = 0.55, P = .01) and a negative effect in progesterone receptor-positive tumors (survival, odds ratios = 2.04, P = .04) is probably ascribable to chance. Analysis of various prognostic factors shows that tumor size and histological grade have a clear effect on both relapse-free interval and survival. PMID- 1627437 TI - Chemotherapy versus observation in high-risk node-negative breast cancer patients. AB - Postoperative women with breast cancer but without histopathological evidence of metastases to the axillary lymph nodes or clinical evidence of metastases were studied. Six hundred fifty-five "good-risk" patients who were estrogen receptor positive (ER+) with primary tumors less than 3 cm were registered for observation. Twenty-four of these patients were treated with chemotherapy. Five hundred thirty-six "poor-risk" patients who were either ER+ with primary tumors greater than or equal to 3 cm or estrogen receptor negative (ER-) with any primary tumor size were randomly assigned between chemotherapy and observation. Randomization was stratified by type of surgical procedure, number of lymph nodes examined, menopausal status, tumor size, and ER status. The chemotherapy (CMFP) consisted of six 4-week cycles of cyclophosphamide, 100 mg/m2 orally days 1-14; methotrexate, 40 mg/m2 intravenously (IV) days 1 and 8; fluorouracil, 600 mg/m2 IV days 1 and 8; and prednisone, 40 mg/m2 orally days 1-14. Treatment arms in the randomly assigned patients were balanced with respect to pretreatment characteristics. This analysis includes 445 eligible patients entered in the registration arm and 425 eligible patients entered into the randomized treatments. The median follow-up is 4.5 years in the randomly assigned cohort and 4.8 years in the registered cohort. The overall 5-year disease-free survival (DFS) among the randomly assigned patients was 83% with CMFP and 61% with observation (P less than .0001). A DFS treatment benefit was observed in premenopausal and postmenopausal patients as well as in patients with ER+ or ER- tumors. There were fewer local-regional and distant relapses among the CMFP treated patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627438 TI - Epilepsy, cerebral blood flow, and cerebral metabolic rate. AB - Penfield's observations in the 1930s provided the first systematic evidence of changes in regional cerebral blood flow (rCBF) associated with focal seizures. Further studies in humans and animals confirmed increases in cerebral blood flow and metabolism during generalised seizures, but the interictal, ictal, and postictal changes in focal epilepsy have begun to be elucidated in the last decade with the advent of in vivo imaging techniques such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) and, in the case of animal studies, of autoradiography. Most studies have been of temporal lobe epilepsy. Interictally, the characteristic finding has been reduced blood flow and/or metabolism in the affected temporal lobe, or more extensively in the ipsilateral hemisphere. The few studies to date of ictal or postictal changes have been of rCBF using SPECT. They show hyperperfusion of the whole temporal lobe ictally, hyperperfusion of the hippocampus, combined with hypoperfusion of lateral structures in the immediate postictal period. Later in the postictal period, hypoperfusion alone is seen. Studies of focal seizures in animals have shown hyperperfusion and hypermetabolism at the site of the focus often with widespread depression of both parameters in the ipsilateral neocortex. Limited studies of coupling between blood flow and metabolism in humans have suggested that flow during seizures is adequate for metabolic demand, although some animal studies have suggested localised areas of uncoupling. The results of modern in vivo imaging of ictal and postictal changes in blood flow and metabolism have correlated well with Penfield's observations, and these changes are now being used to help localise epileptic foci, allowing wider use of the surgical treatment he pioneered. PMID- 1627439 TI - Transcranial Doppler: clinical and experimental uses. AB - Blood flow velocity in the basal intracranial arteries can be reliably recorded using transcranial Doppler (TCD) ultrasonography. The utility of Doppler ultrasound in detecting stenosis of arteries has therefore been extended to include the intracranial basal arteries. This has been useful in detecting intracranial stenosis from a variety of causes including atherosclerosis and vasospasm induced by subarachnoid hemorrhage. Changes in cerebral hemodynamics during significantly increased intracranial pressure have also been detected, and have been useful in warning of compromise of the cerebral circulation in head injury. The assessment of the final hemodynamic effects of occlusive disease on the middle cerebral artery can be studied using the CO2 reactivity test. This offers additional diagnostic information in these patients. The direct detection of intracranial microemboli using TCD is also now possible and this has implications in the management of patients with stroke and transient ischemic attacks. Continuous monitoring of the middle cerebral artery velocity has been useful in indicating relative blood flow changes through this artery under certain specific circumstances. By providing continuous information on relative blood flow changes, the dynamics of the cerebral circulation can be studied in more detail. This has allowed the assessment of cerebral autoregulation, as well as blood flow changes, due to changes in cortical activity induced by visual stimulation. Further research on the dynamics of the human cerebral circulation will be possible using this technology. PMID- 1627440 TI - In vivo and in vitro studies of the dopaminergic system in movement disorders. AB - Over the past 20 years, tritiated radioligand receptor binding has been used to study the relationship between dopamine receptor binding and various movement disorders, in particular Parkinson disease. More recently, in vivo imaging techniques like positron emission tomography and single photon emission computed tomography have been used to study the dopaminergic system in these disorders. This review describes the data that have been obtained using in vivo and in vitro measurements of the dopaminergic system in movement disorders, and examines the relationship between them. The contribution of these techniques to clinical management is described. PMID- 1627441 TI - Radiographic contrast media. PMID- 1627442 TI - Magnetic resonance angiography. AB - Literature of the past year contains several worthwhile papers describing the application of MR angiography techniques to imaging of the vascular system. MR angiography has been performed with two-dimensional time-of-flight, two dimensional phase-contrast, and three-dimensional time-of-flight techniques. With current methodology it appears that a variety of MR angiography techniques are necessary to image the various vascular beds of the vascular system, with the appropriate MR angiography technique determined by the velocity and flow characteristics of the vascular bed of interest. Knowledge of the change in velocity patterns in disease states appears necessary for appropriate pulse sequence selection. Signal loss due to higher motion disorders remains problematic; however, the steady progress in MR angiography techniques suggests that these limitations will be overcome. Efforts are also underway to measure the velocity of blood flow. The potential combination of imaging and functional capabilities makes it likely that MR angiography will be an important technique for assessing the vascular system. PMID- 1627443 TI - Radiologic treatment of abdominal abscesses with fistulous communications. AB - Although percutaneous radiologic drainage of abdominal abscesses is now a well established, standard procedure, several factors may limit its success. These limitations include the absence of a safe anatomic access route, presence of fistulous communications, and association with severe inflammation of organs such as the bowel or the pancreas. This review addresses advances and persisting limitations in the percutaneous management of complex abdominal abscesses. PMID- 1627444 TI - Gallbladder and biliary interventional radiology. AB - The past ten years have seen the introduction of a number of new techniques for the treatment of biliary diseases. In this report, we discuss the roles of both extracorporeal shock-wave lithotripsy and percutaneous treatment of gallstones, and we emphasize the changing role of these techniques since the advent of laparoscopic cholecystectomy. The literature on chemical cholecystectomy is reviewed with particular reference to experience in humans. Biliary endoprosthesis using expandable metallic stents is discussed in patients with benign and malignant biliary obstruction. Finally, we review the role of interventional radiologic procedures on liver transplant patients. PMID- 1627445 TI - Cardiovascular radiology. PMID- 1627446 TI - Doppler echocardiography. AB - In the past year, Doppler echocardiography has continued to transform the "echo laboratory" into a "cardiac imaging and hemodynamics laboratory." Evaluation of blood flow through the cardiac chambers and great vessels is moving from semiquantitative to quantitative. The potential for measuring mitral regurgitant flow more precisely has been demonstrated by evaluating the zone of flow acceleration that occurs on the left ventricular side of the mitral valve. Direct imaging of pulmonary venous return to the left atrium using transesophageal Doppler echocardiography has also allowed more precise quantification of mitral regurgitation. Left ventricular systolic function may be better quantified in patients with mitral regurgitation by calculating the ratio of the change in pressure to the change in time from the continuous wave spectrum of regurgitant flow. The practical application of transmitral flow.in evaluating diastolic function has been applied to cardiac amyloidosis. PMID- 1627447 TI - Interventional radiology. PMID- 1627449 TI - Ultrafast computed tomography of the heart. AB - Recent cardiovascular morphologic studies focus on direct innovative ultrafast CT applications in detecting coronary calcifications and assessing pericardial diseases. In functional studies, quantitation of regional and global indicators of myocardial function and structure, such as wall thickness or thickening, volume, and mass, can be performed using ultrafast CT and MR imaging with similar approaches. Recent ultrafast CT developments illustrate the fact that cardiac tomographic imaging is evolving rapidly. The production of three-dimensional images from tomography, which is still uncommon, has enhanced resolution and wall motion analysis. Applications will have a major impact on the knowledge of cardiac physiology and the understanding of cardiovascular diseases, if not in daily patient care. Further developments in computer-automated analysis from cardiac ultrafast CT or MR images must be carried out to gain clinical acceptance and to facilitate the routine and consistent measurements of the parameters of cardiac function. PMID- 1627448 TI - Myocardial perfusion imaging in the diagnosis of coronary artery disease. AB - The role of myocardial perfusion imaging has been extended from diagnosis to management and prognosis in patients with coronary artery disease. Great emphasis has been placed on improving the accuracy of the test to better define perfusion, viability, and the extent of damage of the myocardium. To achieve this goal, investigators have focused on several areas including imaging technique, in which the accuracy of single-photon emission CT has been compared with that of positron emission tomography; radiopharmaceuticals, in which 201Tl has been compared with 99mTc-sestamibi and 99mTc-teboroxime; stress modalities, in which dipyridamole and adenosine stress have been compared with exercise; myocardial viability, as determined by delayed and reinjection 201Tl imaging or by measurement of cellular integrity using 82Rb compared with 18fluorodeoxyglucose metabolic PET imaging; and assessment of myocardial salvage and prognosis by exercise or dipyridamole 201Tl imaging in acute myocardial infarction. PMID- 1627450 TI - Magnetic resonance imaging of the heart and the great vessels: morphology, function, and perfusion. AB - The capability of MR imaging to evaluate cardiovascular disease is developing faster than ever, as is well documented by the numerous contributions that have been made to the literature during the past year. As the field progresses, MR imaging will probably become one of the preferred investigational methods for the evaluation of cardiac function. The first stage of MR imaging development emphasized replication of commonly used methods for studying morphology and analyzing global ventricular performance. Thus, validated MR imaging methods exist for the assessment of ventricular' volume, ejection fraction, and mean wall stress. More recently, emphasis has been directed toward the evaluation of regional function and perfusion, using novel methods and attracting increasing interest from the cardiovascular research community. Studies reviewed here focus on both clinical results obtained using well-established MR imaging techniques and new results using innovative methods, further extending the usefulness of MR imaging. Topics discussed include congenital and ischemic heart disease and disease of the great vessels. Technical advances in flow and velocity mapping and in the evaluation of ventricular performance are also discussed. PMID- 1627451 TI - Cardiac magnetic resonance spectroscopy. AB - Magnetic resonance spectroscopy provides information about metabolic processes in living tissues. The resulting information may be more sensitive and specific than that obtained using techniques that rely on functional or structural measurements. Although the preponderance of applications to date have been in physiologic investigations in animals, clinical applications are emerging. Reports in the past two years have appeared evaluating the clinical use of phosphorus spectroscopy to detect ischemic heart disease, cardiomyopathy, and cardiac transplant rejection. Active research using nuclei other than phosphorus for spectroscopy will expand the potential clinical applications. Technical developments, including improved surface coil design, wider use of high-field magnets and new pulse sequences, will allow improved sensitivity and spatial localization in the future. PMID- 1627452 TI - Coronary angiography and interventional cardiology. AB - Percutaneous transluminal coronary angioplasty has become the most commonly applied coronary revascularization procedure. Its growth is due to expanding indications and new patient populations including patients with multivessel coronary artery disease, acute myocardial infarction or cardiogenic shock, and elderly patients. Success rates and complications for percutaneous transluminal coronary angioplasty have remained the same or improved despite the expanding indications and the persistent problem of restenosis. Several recent studies have examined new biologic approaches to restenosis. However, the most exciting area of interventional cardiology continues to be the use and development of new mechanical devices including stents, lasers, and atherectomy for unfavorable anatomic lesions, acute occlusion after angioplasty, and to prevent restenosis. The gold standard in the assessment of coronary disease is still angiography, but newer imaging techniques including intravascular ultrasound and angioscopy have added to our understanding of angioplasty, unstable angina, and the use of new devices. PMID- 1627453 TI - Pediatric cardiovascular diagnosis. AB - Significant progress is being made in the field of pediatric cardiovascular imaging. The application of color Doppler transesophageal echocardiography has proven to be extremely useful in both intra- and perioperative examinations. The introduction of the long-axis pediatric probe has expanded the abilities of transesophageal imaging in clinical pediatric practice. MR imaging is continuing to evolve as a noninvasive imaging technique. The development of cine-MR imaging now permits simultaneous evaluation of cardiac anatomy and function and is forecasting a larger role for this technology. In the field of interventional cardiovascular radiology, there have been further reports describing percutaneous balloon valvoplasty both at valve and vascular levels, as well as the application of balloon expandable intravascular stents for a variety of obstructive lesions. PMID- 1627454 TI - Current status and extended applications of intravascular stents. AB - The introduction of several novel techniques and mechanical devices to interventional radiology has expanded the range of therapies for a variety of medical disorders. Intravascular metallic stents have received widespread acclaim and may possess the most potential of all the newest devices available to the interventionist. The addition of metallic stents to the percutaneous therapeutic arsenal provides the interventionist with a device that can resist the elastic recoil of a stenotic vessel or support a newly created vascular tract. Peripheral artery metallic stent placement holds great promise for the treatment of selected patients; other applications of stents, including transjugular intrahepatic portosystemic stent shunts are likely to have a great impact in patient management. We review the techniques, appropriate indications, and recent clinical results of vascular stents for percutaneous intervention and therapy. PMID- 1627455 TI - Peripheral angiography and angioplasty. AB - This paper reviews recent developments in diagnostic and therapeutic interventional procedures for the peripheral arteries reported from February 1991 to January 1992. Topics discussed include endovascular metallic stents, atherectomy catheters, and intravascular ultrasound. PMID- 1627456 TI - Venous imaging and inferior vena cava filters. AB - Thromboembolic disease is a major complication in many hospitalized patients. Imaging of deep venous thrombosis is important for making the diagnosis. After establishing the diagnosis, a decision must be made regarding anticoagulation. If the patient can not be anticoagulated, placement of an inferior vena cava filter is indicated. This paper discusses some of the latest information available on a variety of filters. However, a long-term multicenter study is needed to determine the effectiveness and safety of the available filters. A new approach to percutaneous insertion of central venous catheters is also discussed. PMID- 1627457 TI - Visceral angiography and embolization. AB - New aspects of both diagnostic and therapeutic angiography are reviewed in the context of tumor therapy, trauma, and portal hypertension. The use of intra arterial administration of calcium gluconate as a diagnostic challenge for insulinomas, tumor embolization, and chemoembolization are reviewed. The use of angiography for proximity injuries and the therapeutic aspects of embolization in blunt hepatic, pelvic, and splenic trauma are also noted. Angiography in portal hypertension is emphasized as an adjunct to surgery. The use of the transjugular intrahepatic portosystemic shunt is reviewed and is noted to be of great promise. PMID- 1627459 TI - Variants of human L1 cell adhesion molecule arise through alternate splicing of RNA. AB - The L1 cell adhesion molecule was initially identified and characterized in mouse as a cell-surface glycoprotein that mediates neuron-neuron and neuron-Schwann cell adhesion. We have characterized L1 in humans using cDNA structural and mRNA expression analyses. We present the entire coding sequence for human L1, which predicts a 1253-amino acid protein displaying a signal sequence, transmembrane segment, RGD sequence, and potential glycosylation and phosphorylation sites. Nucleotide and deduced amino acid sequence identities between human and mouse L1 are 85% and 87%, respectively. In contrast, the amino acid identity between human L1 and the L1-related molecule chicken Ng-CAM is only 45%. Using Northern blot analyses, a single L1 transcript of 5.5 kb is detected in human fetal brain and in neuroblastoma (IMR-32) and retinoblastoma (Y-79) cell lines. L1 is also expressed in the rhabdomyosarcoma cell lines RD and A-204, which display several muscle characteristics. Two forms of L1, which differ by the presence or absence of a 12-bp cytoplasmic segment, are expressed in both human and mouse. This segment is encoded by a single exon that can be alternately spliced to give rise to the two forms, which appear to be expressed in tissue-specific patterns. PMID- 1627461 TI - The reeler gene: a clue to brain development and evolution. AB - Reeler mutant mice are characterized by profuse anomalies of cell positioning in the telencephalic and cerebellar cortices as well as by distinct malformations in non-cortical structures such as the inferior olive, the facial nerve nucleus and other brainstem nuclei. Studies of the embryonic development of these structures reveal that the early cell patterns formed by reeler neurons is consistently affected, so that the reeler gene plays an important role in the development of nerve cell patterns. Comparative studies of cortical development in reptiles suggest further that the mammalian type of cortical architectonics has been acquired progressively during brain evolution, and reveal some similarities in early cortical organization between reeler and reptilian, particularly chelonian, embryos, most notably the presence of an inverted gradient of cortical histogenesis. These observations point to a possible role of the reeler gene in cortical evolution. Although the factors responsible for the formation of neural cell patterns are largely unknown, most data point to the importance of cell-cell interactions. Cell-interaction molecules have probably been acquired during brain evolution and the reeler gene could act by perturbing, directly or indirectly, such cell interactions. The characterization and thus the cloning of the reeler gene is therefore important for our understanding of brain development. Recent data on the fine chromosomal mapping of the mutation prior to its positional cloning are reported. PMID- 1627462 TI - Autonomous mesoderm formation in blastocoelic roof explants from inverted Xenopus embryos. AB - Xenopus eggs, artificially fertilized, were prevented from undergoing equilibrium rotation by incubation in medium containing ficoll. Three orientations were selected: normal, with animal pole uppermost; inverted, with vegetal pole away from gravity; and an off-axis orientation, with embryos tilted approximately 90 degrees from the animal-vegetal axis. At blastula stage 8, cells forming the blastocoelic roof were cultured in isolation as explants. These cells are normally fated to from epidermis ventrally and neural derivatives dorsally. Unexpectedly, in the fragments originating from inverted or 90 degrees-off-axis embryos, axial structures were found: notochord, somites, neural cells, cement glands, and sometimes sensory organs. Inverted eggs could be exploited in studies of mesodermal specification. PMID- 1627460 TI - Expression of thymosin beta-4 and related genes in developing human brain. AB - The retinoic acid-responsive thymosin beta-10 gene is known to be developmentally regulated in the human brain. We now report the novel finding that thymosin beta 4, a structurally related 5-kDa actin-sequestering protein, is also subject to a similar but not identical pattern of expression during normal human neuroembryogenesis. However, while thymosin beta-10 mRNA was undetectable (by northern blot analysis) in adult human brain, levels of thymosin beta-4 mRNA, although greatly reduced, were still present. Moreover, a novel thymosin beta-10 like gene was also found to exhibit a unique stage-specific expression during early human neural development. These experiments, together with previous findings, indicate that the products of the two thymosin genes, possibly in association with cytoskeletal elements, may play different roles during early neuroembryogenesis and neural maturation. PMID- 1627458 TI - Molecular and cellular biology of Alzheimer amyloid. AB - Alzheimer's Disease (AD), a disorder of unknown etiology, is the most common form of adult-onset dementia and is characterized by severe intellectual deterioration. The definitive diagnosis of AD is made by postmortem examination of the brain, which reveals large quantities of neurofibrillary tangles (NFT) and senile plaques within the parenchyma. The NFT are composed of paired helical filaments associated with several cytoskeletal proteins. The primary protein component of senile plaques is beta/A4 amyloid, a 42-43 amino acid peptide derived from a much larger molecule, the amyloid precursor protein (APP). Vascular beta/A4 amyloidosis is also prevalent in the disease. The mechanism by which beta/A4 amyloid accumulates in the AD brain is unknown. Recent research has demonstrated that the precursor molecule, APP, is a transmembrane protein with a large extracytoplasmic domain, a membrane spanning region that includes the portion that gives rise to beta/A4 amyloid, and a short intracytoplasmic domain. The precursor has multiple forms among which are those that differ by a variable length insert within the extracytoplasmic domain. The insert has sequence homology to the family of Kunitz protease inhibitor proteins. Cellular and animal models have been developed to study the nature of APP processing and the biological and behavioral consequences of beta/A4 amyloidosis. The results of such studies indicate that the normal processing of APP involves enzymatic cleavage of the molecule within the beta/A4 amyloid region, thus preventing the accumulation of beta/A4 in the normal brain. The factors leading to abnormal processing of APP, and consequent beta/A4 amyloid accumulation within the AD brain, have yet to be identified. In cell culture, the biological effects associated with beta/A4 amyloid include neurotrophic and neurotoxic activities, while the peptide has also been shown to have dramatic behavioral effects in animal models. PMID- 1627463 TI - The arrest of cell migration in the chicken blastoderm: experimental evidence for the involvement of a band of extracellular fibrils associated with the basal lamina. AB - This article overviews our current knowledge of the occurrence and distribution of oriented extracellular fibrils associated with the basal lamina, and their presumptive role in contact guidance of cells in early embryos. To investigate the role of the band of extracellular fibrils situated at the basal side of the epiblast at the cranial edge of the area pellucida of the chicken blastoderm, we determined the precise location and morphology of the fibrils using TEM and SEM, described the relationship between migrating mesoblast cells and the fibrillar band, and, finally, tested experimentally the behavior of homologous and heterologous tissues in the vicinity of the fibrillar band. The descriptive analysis demonstrated that a horseshoe-shaped, 170 microns-wide band of fibrils occurs at the cranial and lateral edges of the area pellucida and area opaca, the highest density being found in the area pellucida. Migrating mesoblast cells presented a surface morphology that was different from the morphology of cells reaching the fibrils at the lateral edge of the area pellucida. Mesoblast cells never crossed the fibrils, an observation that may explain why during gastrulation, mesoblast cells invade the area opaca only in the caudal region, where no fibrillar band is present. The experimental analysis, which involved transplantation and healing experiments, demonstrated that the arrest of cell migration, that occurred in all cases in the vicinity of the fibrillar band, was correlated with changes in surface morphology suggesting a decreased cell adhesion to the fibrils. From these observations emerged the view that the horseshoe-shaped fibrillar band functions as a barrier inhibiting migration of individual mesoblast cells and expansion of tissue sheets, rather than as an extracellular substrate mediating the oriented guidance of cells. In addition to its inhibitory role in cell migration, the extracellular band may also be regarded as a factor that stabilizes the polarity of the early embryo by determining the cranial and lateral limits between embryonic and extraembryonic tissues. PMID- 1627464 TI - Location of DNA within the nucleolus of rat oocytes during the early stages of follicular growth. AB - We have investigated the DNA distribution within the rat oocyte nucleolus during the early stages of follicular growth by means of the in situ terminal deoxynucleotidyl transferase method. In the fibrillogranular nucleolus, label is visualized on small clumps of peri- and intranucleolar chromatin. Such labeled clumps are frequently observed inside the interstices surrounding the fibrillar centers. Label is also consistently found in the fibrillar centers whereas the dense fibrillar component and the granular component are devoid of gold particles. These results contradict earlier data but conform with other recent immunocytochemical observations, obtained in nucleoli of a variety of somatic cell types, concerning the correlation between structure and function in the nucleolus. PMID- 1627465 TI - Biochemical characterization of subcellular particles in fetal and neonatal rats. AB - By a variety of methods, such as ultracentrifugation in different media, hypoosmotic activation and hydrostatic compression, subcellular particles were characterized at different perinatal ages and compared to the adult rats. Fetal mitochondria elicited a higher density, an increased osmotic space and a greater resistance to compression. The size of these particles was larger than in the adults. Mitochondria in the 1-day-old animals were freely permeable to sucrose and their external membrane was more resistant to hypoosmotic activation. Lysosomes were shown to decrease their sucrose permeability and their resistance to hypoosmotic activation with development. Moreover, the size of the lysosomes increased with development. PMID- 1627466 TI - Evolution of the developmental scores of sixteen morphological features in mouse embryos displaying 0 to 30 somites. AB - A precise framework of morphological developmental events observed macroscopically in early postimplantation mouse embryos aged 8-10 days (0-30 somites) is established. The quantitative evolution of the developmental score of 16 features as a function of the developmental stage of the embryos (expressed in number of somites) is presented. Thirty-one groups of ten embryos, each with 0 to 30 somites, were scored for each feature according to the previous description of the authors. In addition, the variation of individual structures as a function of embryonic developmental stages is evaluated. It is suggested that the framework of differentiating individual structures at given developmental stages will help to plan experiments in developmental biology of rodents and will facilitate the interpretation of results in developmental toxicity. PMID- 1627467 TI - A new interpretation of the necrotic changes occurring in the developing limb bud paddle of mouse embryos based upon recent observations in four different phenotypes. AB - Degenerative changes occurring in the apical ectodermal ridge (a.e.r.) and undifferentiated distal mesoderm of developing limb buds were studied macro- and microscopically in day-11 to day-13 mouse embryos displaying the normal (+/+), oligosyndactylous (Os/+), polydactylous (Xpl/+) and hybrid (Os/+/Xpl/+) phenotypes. Isolated limb buds were submitted either to supravital staining with Nile blue sulfate or to lectin binding staining in serial paraffin sections, taking advantage of strong binding affinites of macrophage cells for peanut agglutinin after neuraminidase treatment and for ricinus communis agglutinin. Necrotic changes detected in three definite areas of the distal mesoderm of normal limb buds exhibit characteristic spatial temporal relationships with earlier cytolytic changes affecting the pre- and postaxial parts of the a.e.r. Two of them, known as the primary preaxial site (fpp) and the anterior marginal necrotic zone (AMNZ) appeared deeply modified in mutant embryos as compared to the posterior marginal necrotic zone (PMNZ) which remained unaffected. Macrophage cells loaded with cell debris appear in advance and in excessive number in the fpp of Os/+ limb buds. Conversely, they were found absent or locally reduced in number in the fpp and AMNZ of Xpl/+ limb buds which otherwise develop in the same area a preaxial protrusion covered with a healthy portion of the a.e.r. Hybrid Os/+/Xpl/+ limb buds expressing both mutant genes develop a smaller and macrophage-free preaxial protrusion which coexists with residual and locally excessive necrotic changes in its immediate surrounding and is covered with a normally necrotic portion of the a.e.r. Microscopic observations collected in the limb buds of all phenotypes, though more frequently in Os/+ limb buds, strongly suggest that in all three necrotic sites examined, macrophage cells of vascular origin somehow contribute to the clearance of ectodermal necrotic debris and eventually return in the blood stream through the marginal vein and its affluents. PMID- 1627468 TI - The Brussels School of Embryology. PMID- 1627470 TI - Review of scientific contributions by the Belgian medical centers concerned with human in vitro fertilization and embryo transfer (IVF). AB - In vitro fertilization and embryo transfer (IVF) may be considered as a particular application of modern medical therapeutics linked to human reproduction. The treatment of human sterility therefore involves some fundamental human values such as life, love and death. The quality of this highly technological treatment with fast knowledge of outcome at the end of the patient's menstrual cycle has been evaluated since the early 80s. It is a typically multidisciplinary team effort involving medical doctors, biologists, laboratory technicians, nurses and clerks that is representative of modern medical practice. IVF covers much more than just embryology, as this review will explain. IVF developed in close relation with clinical and experimental research protocols, which are the major topics of this paper. The newness of the techniques used led to the necessary interactions between clinicians and biologists working on animal experimental embryology. PMID- 1627469 TI - In vitro production of cattle embryos: review and Belgian results. AB - This paper reviews the overall process of in vitro production and cryopreservation of bovine embryos in Belgium. Three laboratories are involved in this field, one at the University of Liege, one at the University of Ghent and ours at the University of Louvain-La-Neuve. Each one uses this technology as a tool to reach different goals. This paper refers mainly to the work done in Louvain-La-Neuve. Oocytes are obtained by punction of 2-4 mm follicles on slaughtered cow ovaries. They are matured in hormone-supplemented TCM199 containing 10% heat-treated fetal calf serum. In vitro fertilization by Percoll selected spermatozoa is followed by in vitro culture in oviduct-conditioned medium for 7-9 days. Six calves have been born from in vitro produced blastocysts. Recently, full development was obtained in conditioned medium without protein supplementation. This finding will allow further investigations on oviduct/embryo molecular communication and research of oviduct-secreted embryotrophic proteins which were impaired in previous culture systems using serum-supplemented media. In vitro produced blastocysts were frozen-thawed and non-surgically transferred: 7/19 recipients remained pregnant beyond 2 months. Embryo loss was high between day 21 and 35 (31%). PMID- 1627471 TI - A pioneer of experimental mammalian embryology: Jacques Mulnard. PMID- 1627472 TI - Jean Brachet and his school. PMID- 1627473 TI - Lucien Vakaet, an avian embryologist. PMID- 1627475 TI - Research and the teaching of developmental biology in Belgium. PMID- 1627474 TI - The developmental biology of neural connectivity. AB - How can the development of an ordered array of neuronal connections be encoded in the genome? Results on the establishment of sensory connections in insects indicate that this programming is a multi-stepped process which begins as soon as the first axons develop. Because each step relies on the previous level of organization, the first steps of the process are subject to intense structural constraints, and therefore have been largely conserved through evolution. What is known of the molecular biology of some essential steps, like the differentiation of excitable cells, their aggregation in nerve cords, and the diversification of a periodic structure, supports the idea that the basic organization of the CNS evolved before the divergence between the chordate and the arthropod/annelid lineage. PMID- 1627476 TI - Molecular genetic approaches to plant development. AB - Higher plant morphogenesis has received renewed interest over the past few years. The improvement of molecular genetic approaches to generate tagged developmental mutants, for instance by T-DNA insertion, facilitated the isolation and characterization of the altered genes. Here we present recent progress on flower and root morphogenesis in the small crucifer Arabidopsis thaliana. The current model of Arabidopsis flower development is presented. We report on FLOWER1 (Fl1), which is a T-DNA-tagged ap2 allele. Our observations indicate that this Fl1 mutant has, besides the homeotic Ap2 phenotype, an aberrant seed coat, suggesting that this gene has also a function late in flower development. Furthermore, we present a brief summary about root development and focus on the super root (Sur) mutant, which is an ethyl methanesulfonate-induced mutant that produces excess lateral roots. Root explants of the Sur mutant, that do not develop further than the 4-leaf stage, can be induced to produce normal-looking shoots and flowers by addition of only cytokinin to the medium. The phenotype of Sur and its relation to the action of phytohormones is discussed. PMID- 1627477 TI - Controlling cellular development in a single cell system of Nicotiana. AB - Cells regenerated from freshly isolated leaf mesophyll protoplasts can be induced to develop along very different pathways. Depending on the hormone content and the mechanical characteristics of the environment, cells choose between division and expansion. In the former case they form microcolonies of isodiametric cells, while in the latter they exhibit a typical tubular growth or increase their volume considerably by bulging and budding. A culture method was developed which allows a careful control of the experimental environment and non-destructive high resolution monitoring of development of individual cells. PMID- 1627478 TI - Plant protoplasts as genetic tool: selectable markers for developmental studies. AB - Protoplasts have usually been presented as a methodological tool. Even as such, they make possible an impressive array of applications in plant biology. Here we report on the use of protoplast-derived selectable markers in the study of several disturbed genetic systems with obvious effects on plant development: (1) auxotrophic mutants and the control of amino acid biosynthesis and transport in vegetative and reproductive tissues; (2) introgression of alien genetic information across phylogenetic boundaries by protoplast fusion, a consequence of controlled dedifferentiation-redifferentiation processes and attenuated incompatibility reactions in cultured cells; (3) expression (in)stability of foreign genes in transgenic plants during successive meiotic generations and in crosses between independent transformants. PMID- 1627479 TI - The determination of sense organs in Drosophila: a search for interacting genes. AB - The determination of sense organs in Drosophila requires the concerted action of a battery of genes, several of which have been identified. Previous experiments revealed that flies doubly heterozygous for mutations in two of these genes have a reduced number of sense organs, suggesting the existence of a direct interaction between the corresponding genes and/or their products. We have now used this observation to search for mutations in additional genes that would show similar interactions. We have detected 10 recessive mutations that show a dominant reduction in the number of bristles when simultaneously heterozygous for either Df(2)J27 or Df(4)M62f. Among these mutations, 3 are homozygous viable and show striking defects in their bristle patterns, confirming that the genes thus identified play a role in the patterning of sense organs. We conclude that the "gene dose titration" method (Botas et al., 1982) is an efficient method for identifying interacting genes involved in a common process, provided one can identify a well-defined phenotype to look at, and at least one mutation that alters the process. Our experience suggests that its efficiency should be substantially improved by the use of insertional mutagenesis. PMID- 1627480 TI - The discovery of meiosis by E. Van Beneden, a breakthrough in the morphological phase of heredity. PMID- 1627481 TI - 17th annual scientific meeting of the British Oncological Association, in association with the Nordic Cancer Societies. Canterbury, 5-7 July 1992. Abstracts. PMID- 1627482 TI - [Epilepsy in children]. PMID- 1627483 TI - [Inhalation devices for fixed dosage aerosols with disodium cromoglycate]. PMID- 1627484 TI - [The 3 year basic training in pediatric nursing has to be retained]. PMID- 1627485 TI - [Parents at the intensive care unit]. PMID- 1627486 TI - [Multiple lentigines syndrome (LEOPARD syndrome)]. PMID- 1627487 TI - [Poisonous and less poisonous plants. I]. PMID- 1627488 TI - [Heinz Hungerland (1905-1987)]. PMID- 1627489 TI - [Admission to nursing in foreign countries]. PMID- 1627490 TI - [Medical terminology and nursing documentation]. PMID- 1627491 TI - [Preparation of baby bottles and nipples]. PMID- 1627492 TI - Selection against N-region diversity in immunoglobulin heavy chain variable regions during the development of pre-immune B cell repertoires. AB - The generation of Ig heavy chain chain diversity is dependent on the ordered rearrangement of three different, i.e. variable (VH), diversity (DH), and joining (JH), germline gene segments, exonuclease nibbling of the terminals of these gene segments, and the addition of template-independent nucleotide (N-sequences) in the junctions of these segments. The latter process has recently been reported to be limited within B cells formed during early ontogeny. In this study, we have analysed a large number of VHDJH rearrangements isolated from genomic DNA of adult and neonatal C57BI/6 mice using the polymerase chain reaction (PCR) technique. A comparison of functional versus non-functional VHDJH rearrangements derived from these PCR libraries, or from a set of previously published clones of BALB/c origin, revealed a selection against N-region diversity both in neonatal and adult B cell repertoires. This selection process is most pronounced in the early development of the immune system but can still be observed in the adult. Furthermore, selection against N-sequence additions was evident amongst neonatal VHDJH rearrangements utilizing both VH 7183 and VH J558 genes, but only in VH 7183 utilizing clones of adult origin. These results imply that in addition to a developmentally controlled onset of N-sequence additions, cellular selection against N-region diversity exist both in the neonatal and adult immune system. PMID- 1627493 TI - Limited repertoire of utilized VH gene segments in a VHa3-allotype-suppressed rabbit. AB - Between 70 and 90% of serum Ig molecules of normal laboratory rabbits bear one of the serologically defined VHa allotypic specificities, a1, a2, or a3, and are termed VHa+ (a-positive) molecules; the remaining 10-30% of Ig molecules that do not have VHa allotypic specificities are designated VHa- (a-negative). The repertoire of utilized VHa(+)-encoding gene segments has been examined extensively, but only limited studies of the repertoire of utilized VHa(-) encoding gene segments in normal rabbits have been done. To examine the repertoire of utilized VHa- gene segments, we analyzed VH-encoding cDNA clones from mRNA of a VHa-allotype-suppressed rabbit whose serum Ig was primarily VHa-. For VHa suppression a newborn a3/a3 rabbit was injected periodically with anti VHa3 antiserum; when it was 2 months of age and its serum Ig was greater than 94% VHa-, cDNA clones were generated from splenic RNA. The nucleotide sequences of eight putative VHa(-)-encoding cDNA clones were compared to those of eight cDNA clones generated from RNA of non-suppressed a3/a3 rabbits. The presumed VHa3 encoding cDNA clones from the non-suppressed rabbits appeared to derive from VH1 a3, the 3'-most germline VH gene segment. In contrast, the VHa(-)-encoding cDNA clones from the suppressed rabbit were distinctly different from VH1 and were most probably derived from germline VH segments other than VH1. Because the expressed VHa- gene repertoire was highly restricted, we propose that VHa- molecules in a3/a3 rabbits may be derived from as few as three germline VH gene segments. PMID- 1627494 TI - Differential effects of IL-4 and IL-10 on IL-2-induced IFN-gamma synthesis and lymphokine-activated killer activity. AB - Culture of human peripheral blood mononuclear cells (PBMC) with IL-2 stimulates synthesis of cytokines and generation of lymphokine-activated killer (LAK) activity. Both IL-4 and IL-10 [cytokine synthesis inhibitory factor (CSIF)] inhibit IL-2-induced synthesis of IFN-gamma and tumor necrosis factor (TNF)-alpha by human PBMC. However, unlike IL-4, IL-10 inhibits neither IL-2-induced proliferation of PBMC and fresh natural killer (NK) cells, nor IL-2-induced LAK activity. Moreover, IL-4 inhibits IL-2-induced IFN-gamma synthesis by purified fresh NK cells, while in contrast the inhibitory effect of IL-10 is mediated by CD14+ cells (monocytes/macrophages). IL-10 inhibits TNF-alpha synthesis by monocytes or monocytes plus NK cells, but not by NK cells alone. These results suggest that IL-4 and IL-10 act on NK cells via distinct pathways, and that IL-2 induced cytokine synthesis and LAK activity are regulated via different mechanisms. PMID- 1627495 TI - Distinct mechanisms of extrathymic T cell tolerance due to differential expression of self antigen. AB - Self-reactive T lymphocytes escaping thymic tolerance induction can be rendered non-responsive by contact with antigens in the periphery. In order to determine the parameters controlling peripheral tolerance induction we followed the fate of one well-defined self-reactive T cell population in three different mice expressing the self antigen in various nonlymphoid tissues outside the thymus. This was achieved by crossing anti-Kb T cell receptor (TCR) transgenic mice with transgenic animals expressing the Kb antigen exclusively on hepatocytes or keratinocytes or neuroectodermal cells. Due to this differential expression clonotype+, anti-Kb reactive T cells were found to exist at three different levels of tolerance. These levels were distinct with regard to downregulation of TCR and CD8 molecules, and the requirements for reexpression of TCR in vitro. This differential induction of peripheral tolerance suggest that some tissues are more likely to be affected in autoimmune diseases than others. PMID- 1627496 TI - Transfer of both protection and delayed-type hypersensitivity against live Listeria is mediated by the CD8+ T cell subset: a study with Listeria-specific T lymphocytes recovered from murine infected liver. AB - The recruitment of specific T lymphocytes in murine liver is thought to be a key event in the ultimate control of Listeria monocytogenes growth during primary infection. However, there has been little functional characterization of the cell populations recruited in this non-lymphoid organ. Therefore in this study, the recruited lymphomyeloid cells were isolated from the liver of C57BL/6 mice at the peak of the immune response (day 7) triggered by a non-lethal L.monocytogenes infection. The anti-Listeria T lymphocytes were detected in vivo by their ability to transfer protection and delayed-type hypersensitivity (DTH) to live L.monocytogenes in naive recipients: protection was measured not only by the effect on reduction of the bacterial load in liver and spleen, but also on survival after the lethal challenge, and DTH was detected using as eliciting antigen, either live L.monocytogenes or heat-killed L.monocytogenes. When live pathogens were used, both functions were found to be mediated by T lymphocytes belonging to the CD8+ subset. However, when heat-killed L.monocytogenes were used as eliciting antigen in the DTH assay, Listeria-specific CD8+ T lymphocytes could not be restimulated in immune lymphoid cell populations recovered either from liver or spleen of Listeria-infected mice. Both populations were thus found to share the same qualitative properties in the DTH assay. The importance of the use of live pathogens versus heat-killed pathogens for detection of DTH and protection functions is discussed in the light of current concepts on processing and presentation pathways of Listeria-derived peptides. PMID- 1627497 TI - Does CD4 help to maintain the fidelity of T cell receptor specificity? AB - During antigen presentation, a close association between CD4 and the T cell receptor (TCR) occurs as a result of interacting with the same major histocompatibility complex class II molecule. The potential consequences of such an intimate interaction on TCR specificity was addressed using CD4 loss variants of four different murine T cell hybridomas specific for the immunodominant hen egg lysozyme (HEL) peptide 46-61. While all the CD4+ and CD4- variants tested possessed comparable surface expression of TCR, CD3, CD2 and LFA-1, and responded similarly to immobilized anti-TCR and anti-CD3 monoclonal antibodies, they differed dramatically in their responses to either the naturally processed HEL antigen, synthetic peptide 46-61 or staphylococcal enterotoxin superantigens. While one hybridoma was comparatively unaffected by the loss of CD4, another lost its responsiveness to antigen and peptide completely while retaining reactivity to SE. In contrast, two other hybridomas still responded to antigen but lost reactivity to synthetic peptide and SE. These data could not be readily explained on the basis of affinity or signal transduction requirements alone, and thus suggest that the intimate association of CD4 with the TCR may result in a subtle modulation of its fine specificity for some but not all T cells. PMID- 1627498 TI - [Natural killer cell activity in mice infected with Acanthamoeba culbertsoni]. AB - The natural killer cell activity of splenocytes and TBC, active NK cells, recycling capacity of natural killer cells were observed by means of both the 51Cr-release cytotoxicity assay and single cell cytotoxicity assay against YAC-1. C3H/HeJ mice were infected intranasally with 1 x 10(4) or 1 x 10(5) trophozoites of pathogenic Acanthamoeba culbertsoni. The infected mice showed mortality rate of 34% in 1 x 10(4) group and 65% in 1 x 10(5) group, and mean survival time was 16.40 +/- 3.50 and 13.20 +/- 4.09 days respectively. The cytotoxic activity of natural killer cells of the 2 groups was significantly higher than that of non infected mice from the 12th hour to the 2nd day after infection, showing the highest on the first day. On the 10th day after infection, the cytotoxic activity of natural killer cells was significantly suppressed as compared with that of the control. There was no significant difference in NK cell cytotoxicity between two infected groups. The target-binding capacity and active NK cells of natural killer cells in 1 x 10(5) trophozoite infected mice was significantly increased on the 12th hour and the first day after infection as compared with the control group. Maximal recycling capacity (MRC) was not changed during the observation period. The present results indicated that the elevation of natural killer cell activity in the mice infected with A. culbertsoni was due to elevation of target binding capacity and increased active NK cells of natural killer cells, and not due to the maximal recycling capacity of the individual NK cell, and there was no difference between two experimental dose groups. PMID- 1627499 TI - [The protective effects of monoclonal antibodies in mice from Naegleria fowleri infection]. AB - Protective effects of monoclonal antibodies against N. fowleri were comparatively studied. BALB/c mice were treated with two types of monoclonal antibodies, Nf 2 and Nf 154, before and after the infection with N. fowleri. The mortality and mean survival times were then compared. Also, direct effect of the monoclonal antibodies on the N. fowleri trophozoites in vitro were observed. In vitro protective effects of the monoclonal antibodies were also studied in cells infected with N. fowleri. The observed results are summarized as follows: 1. Among mice pretreated twice before the infection with monoclonal antibody Nf 2(McAb Nf 2), only 15.8% were killed, and the mean survival time was 17.7 days. This was not much different from the mice pretreated once, as the mortality and mean survival time were 16.7% and 17 days. Those effects were compatible with monoclonal antibody Nf 154(McAb Nf 154). The above findings contrast with the mortality and mean survival time of the control mice, which were 22.7% and 14.6 days respectively. 2. Mice which received twice the McAb Nf 2 following N. fowleri infection incurred a 19.4% mortality rate with 13.6 days survival time; 17.9% and 15.8 days with on time administration, in contrast to the 25% and 14.6 days in the control group. 3. Marked agglutination effect of McAb Nf 2 or McAb Nf 154 were observed on N. fowleri trophozoites. 4. When N. fowleri trophozoites were treated with McAb Nf 2 or McAb Nf 154 combined with comments, the proliferation rate was more significantly suppressed than in that the control. 5. N. fowleri trophozoites treated with McAb Nf 2 or McAb Nf 154 showed an increased number of swollen mitochondria, disfigured cisternae, lipid droplets, and osmiophilic granules in the cytoplasm. 6. A remarkable protective effect of monoclonal antibodies was noticed in CHO cells infected with N. fowleri. More than 90.6% of the infected CHO cells survived, contrasted with 27% of untreated cells. The overall results in this study suggest that N. fowleri treated with monoclonal antibodies against N. fowleri reduce the mortality and prolong the survival time of the mice when the antibodies are administered before the infection. The protective effect of the monoclonal antibodies is surmised being caused by agglutination of the trophozoites. PMID- 1627500 TI - [Changes in blastogenic responses and antibody titers of mice infected with Toxoplasma gondii]. AB - This study was performed to observe the cell-mediated and humoral immune responses in mice which were infected with Beverley, Fukaya and ME49 strain of Toxoplasma gondii, respectively. The blastogenic responses of splenocytes using [3H]-thymidine and serum antibody titers were measured weekly up to 10 weeks after infection. The blastogenic responses of splenocytes treated with concanavalin A and Toxoplasma lysate were significantly declined in the 3 strain groups as compared with the non-infected group (p less than 0.05), however lipopolysaccharide-treated blastogenic responses were not significantly different between infected and non-infected groups. The serum IgG antibody titers in the three infected groups increased from 2 weeks after infection, and the serum IgM antibody titers increased until 4 weeks after infection. No significant differences were revealed in blastogenic responses and serum antibody titers among the 3 groups. The present study suggested that cell-mediated immune responses were involved in T. gondii infected mice and blastogenic responses of T lymphocytes were inhibited in acute T. gondii infection. PMID- 1627502 TI - [Comparative study on the effectiveness of modified Kato's cellophane thick smear and Stoll's dilution egg counting technique for quantitative fecal examination of helminth eggs]. AB - A total of 197 fecal specimens was prepared for quantitative examination of helminth eggs by modified Kato's cellophane thick smear (M.C.T.S.) and Stoll's dilution egg counting technique (D.E.C.T.). The comparative effectiveness of two techniques was evaluated and conversion function was deduced. The average time required for the microscopic examination on one slide by M.C.T.S. was 12.6 minutes and that of D.E.C.T. was 14.6 minutes. M.C.T.S. showed lower false negative rate than D.E.C.T. in light worm burden cases. Functions to convert the counts obtained by M.C.T.S. to E.P.G. by Stoll's dilution egg counting technique were 47.86 x 10(0.87) logM.C.T.S. in A. lumbricoides, 41.69 x 10(0.82) logM.C.T.S. in T. trichiura and 63.10 x 10(0.85) logM.C.T.S. in C. sinensis. It was suggested M.C.T.S. be better than D.E.C.T. for the quantitative examination of intestinal helminthiases such as A. lumbricoides, T. trichiura, and C. sinensis infections even in the cases with low worm burden. PMID- 1627501 TI - Immunogenicity and protective efficacy of solubilized merozoite-enriched Theileria sergenti immunogens. I: Protection against homologous stabilate challenge. AB - Theileria sergenti were isolated from infected erythrocytes by hypotonic lysis, and soluble merozoite antigens were purified by sonication and differential centrifugation. The preparation contained 29, 34, 35 and 105 kD immuno-dominant poly-peptides. The soluble antigens (0.5 mg/ml) were prepared and fortified with Freund's adjuvant. Five month old naive Korean calves were subcutaneously inoculated with the preparation and a booster dose was administered 4 weeks later. Nine weeks after the booster dose, vaccinates and controls were challenged with a homologous stabilate (5.6 x 10(6) RBC/dose, 40% Parasitemia). All animals were monitored for hematocrit, total erythrocyte count, parasitemia and for the specific antibody by Western immunoblot (WB) and indirect immuno-fluorescent antibody (IFA) test. By 18 weeks after vaccination (6 weeks after the challenge), vaccinated cattle had an average IFA titer of 1:10,240 compared with 1:1,280 of the controls. The vaccinates showed negligible change in hematocrit and total RBC count whereas control animals showed significant (p less than 0.05) hematological changes and associated anemia. After vaccination and challenge, the antibody responses demonstrated that vaccination had induced significant production of antibody to the 29 and 35 kD polypeptides. The latter polypeptide was much more strongly recognized by the vaccinated animals, and thus it may be a potential candidate for the vaccine. PMID- 1627503 TI - Second case of human infection with Mesocestoides lineatus in Korea. AB - The second case of human infection with Mesocestoides lineatus in Korea was reported. The patient, a farm worker, complained of abdominal pain and massive discharge of sesame-like proglottids in his stool for several months. Worms, recovered by chemotherapy with niclosamide, consisted of 32 strobilae. This may be the heaviest worm burden in human infection ever reported. The infected man habitually ate the raw viscera of chickens. PMID- 1627505 TI - [Tegumental ultrastructure of juvenile and adult Echinostoma cinetorchis]. AB - The tegumental ultrastructure of juvenile and adult Echinostoma cinetorchis (Trematoda: Echinostomatidae) was observed by scanning electron microscopy. Three day (juvenile) and 16-day (adult) worms were harvested from rats (Sprague-Dawley) experimentally fed the metacercariae from the laboratory-infected fresh water snail, Hippeutis cantori. The worms were fixed with 2.5% glutaraldehyde, processed routinely, and observed by an ISI Korea DS-130 scanning electron microscope. The 3-day old juvenile worms were elongated and ventrally curved, with their ventral sucker near the anterior two-fifths of the body. The head crown was bearing 37-38 collar spines arranged in a zigzag pattern. The lips of the oral and ventral suckers had 8 and 5 type II sensory papillae respectively, and between the spines, a few type III papillae were observed. Tongue or spade shape spines were distributed anteriorly to the ventral sucker, whereas peg-like spines were distributed posteriorly and became sparse toward the posterior body. The spines of the dorsal surface were similar to those of the ventral surface. The 16-day old adults were leaf-like, and their oral and ventral suckers were located very closely. Aspinous head crown, oral and ventral suckers had type II and type III sensory papillae, and numerous type I papillae were distributed on the tegument anterior to the ventral sucker. Scale-like spines, with broad base and round tip, were distributed densely on the tegument anterior to the ventral sucker but they became sparse posteriorly. At the dorsal surface, spines were observed at times only at the anterior body. The results showed that the tegument of E. cinetorchis is similar to that of other echinostomes, but differs in the number and arrangement of collar spines, shape and distribution of tegumenal spines, and type and distribution of sensory papillae. PMID- 1627504 TI - The maintenance of free-living amoebae by cryopreservation. AB - We have successfully cryopreserved free-living amoebae in order to maintain them feasibly under the conditions in our laboratory. The viability of trophozoites was higher when frozen by slow cooling (overall 0.7 degree C/min) than by fast cooling (overall 1.3 degrees C/min). Glycerol and dimethylsulfoxide at the final concentration of 7.5% each was used for cryopreservation of free-living amoebae trophozoites. The survival rate was 2-39% after storage in the liquid nitrogen for 60 days. Gross cultural or morphological changes were not noted in trophozoites thawed from frozen suspensions. PMID- 1627506 TI - Surface ultrastructure of Heterophyes nocens (Trematoda: Heterophyidae). AB - The surface ultrastructure of Heterophyes nocens (Trematoda: Heterophyidae) was studied by scanning electron microscopy(SEM). The adult worms were recovered from experimentally infected cats and from a naturally infected patient. They were leaf-like, ventrally concave, and ovoid or pyriform in shape. Ciliated knob-like sensory papillae (type I) were observed in single or grouped forms on and around the oral sucker, whereas non-ciliated round swellings (type II papillae) were seen on the lip of the ventral sucker. The tegumental spines around the oral sucker were 5-9 pointed, whereas those between the two suckers were 12-17 pointed. Ventrolaterally, three groups of 5-6 type I papillae were located between the oral and ventral suckers, with single ones alternating between them. The genital sucker was protruded or depressed, depending on the contraction state of the flukes, and the gonotyl spine number ranged 50-60. The number of tip points of tegumental spines was decreased posteriorly; finally they became 1-3 pointed. On the dorsal surface, 4 groups of 4-5 type I papillae were symmetrically located on both lateral sides, and the shape and distribution of tegumental spines were similar to those of the ventral surface. Although the tegumental ultrastructure of H. nocens was generally similar to those of other heterophyids, the genital sucker morphology including the number of gonotyl spines and/or the distribution pattern of tegumental spines and sensory papillae were suggested to be the characteristic features of H. nocens. PMID- 1627507 TI - Detection of antibodies in serum and cerebrospinal fluid to Toxoplasma gondii by indirect latex agglutination test and enzyme-linked immunosorbent assay. AB - Sensitivity of anti-Toxoplasma antibody (IgG) test by enzyme-linked immunosorbent assay (ELISA) was evaluated in comparison with indirect latex agglutination (ILA) using 2,016 paired human samples of serum and cerebrospinal fluid (CSF). The samples were collected from neurologic patients in Korea with mass lesions in central nervous system (CNS) as revealed by imaging diagnosis (CT/MRI). When the sera were screened for anti-Toxoplasma antibody by ILA, 76 cases(3.8%) were positive (1:32 or higher titers). In the paired samples of CSF, no positive reactions were observed. When ELISA was performed using PBS extract of Percoll purified tachyzoites as antigen, cut-off absorbance was determined as 0.40 for serum and 0.27 for CSF tests. The antibody positive rates by ELISA were 7.0% in serum and 5.6% in CSF. Of them, 40 cases (2.0%) showed positive reactions in both serum and CSF. The antibody positive rates were higher in groups older than 40 years. The rates were higher in male (4.7% by ILA, 8.3% by ELISA) than in female (2.2% by ILA, 5.0% by ELISA). The rates in CSF showed no such sex difference. ELISA showed twice higher positive rates when serum was tested, and was sensitive enough to detect specific antibodies in CSF. Etiologic relations between positive antibody tests and CNS lesions remained unknown. PMID- 1627508 TI - Tissue origin of soluble component proteins in saline extract of adult Paragonimus westermani. AB - Tissue origin of individual component proteins in crude extract of adult Paragonimus westermani was investigated. Major soluble component proteins were separated by disc-PAGE in 8% slab gel. By predefined Rf values, strips of gel containing each band protein was cut out. Each band protein was eluted by electrophoresis. Monospecific antibodies were prepared by immunizing rabbits with each band protein. When peroxidase-antiperoxidase (PAP) staining was done, antiserum to Band 1 reacted to content of eggs both in the worm and in the infected lung tissue. Antiserum to Band 2 reacted to parenchymal tissue of the worm. Antiserum to Band 4 showed the positive reaction at intestinal content while that to Band 5 reacted to the intestinal epithelial border. Antiserum to combined proteins of Bands 6/7 and that to Band 8 reacted to parenchymal tissue of the worm respectively. From the results, the origin of individual proteins in crude extract of adult P. westermani could be differentiated. PMID- 1627509 TI - Lacrimal lesions and orbital surgeons. PMID- 1627510 TI - The pattern electroretinogram in glaucoma and ocular hypertension. AB - Thirty one eyes with established glaucoma, 61 high risk ocular hypertensive (OHTs) eyes, 66 medium risk OHT eyes, 58 low risk OHT eyes, and 47 control eyes have been followed for up to 2 years by clinical examination and pattern electroretinography (PERG). The study was 'masked' so electrophysiological and clinical data were kept separate. Criteria have been devised which enable PERG measurements to distinguish all established glaucomatous eyes from all normal controls; these criteria demonstrate abnormalities in some OHT eyes, particularly those at high risk. The PERG abnormality is greatest in eyes with established glaucoma in which the intraocular pressure has been lowered by treatment. The PERG becomes smaller as the degree of clinical abnormality increases. Test-retest variability of the PERG is sufficiently low to ensure that most of those first described as abnormal continue to be so. PMID- 1627511 TI - Dermofat grafts to the extraconal orbital space. AB - Dermofat grafts were placed in the upper or lower lid sulci in 35 subjects, aged from 11 to 59 years, to improve the cosmesis of volume deficient sockets or prevent tissue adhesion. Volume enhancement and cosmetic improvement were achieved in 31 patients, in whom useful vision was present in 13/22 after previous trauma, in 4/4 with facial clefting, and in 3/3 with orbital or facial fat atrophy. Grafts were used successfully in nine patients to prevent scar formation after division of adhesions between the eyelids or levator muscle and the orbital margins. A reduction of the bulk of upper-lid grafts was required in three cases; histopathology of the excised fat showed relatively minor degrees of inflammation, atrophy, and fibrosis. PMID- 1627512 TI - Endophthalmitis following extracapsular cataract surgery: a review of 32 cases. AB - Thirty two cases of endophthalmitis following extracapsular cataract surgery that had occurred within our department and had undergone intraocular diagnostic tap between May 1982 and May 1991 were reviewed. An infectious agent was identified in 20 cases (62.5%). The commonest organism was Staphylococcus epidermidis (11 cases) (55%). Proteus was the only gram negative organism identified (four cases) (20%). Both of these organisms were associated with a favourable visual outcome. In the culture positive subgroup 15 eyes (75%) achieved a final acuity of 6/60 or better with 10 eyes (50%) gaining 6/12 or better. Thirteen (65%) of the culture positive cases were managed without vitreal intervention. Of these 11 (85%) achieved 6/60 or better with eight (62%) gaining 6/12 or better. It appears that when an endophthalmitis follows uncomplicated extracapsular cataract surgery delivery of antibiotic by the 'conventional' routes (topical, subconjunctival and systemic) is consistent with a favourable visual result in many cases. A modified anterior chamber diagnostic tap technique is described. PMID- 1627513 TI - Possible environmental sources of Acanthamoeba spp in contact lens wearers. AB - The water supply and dust samples from the home environment (bathrooms and kitchens) of 50 wearers of contact lenses (CLs) were cultured for the presence of free-living amoebae. CL cases, solutions, and water taps were cultured for bacteria, which amoebae require for growth. Acanthamoeba spp were isolated from water drawn from six bathroom cold water taps (tank supplied), five in the presence of limescale, and from one kitchen cold water tap (mains supplied). There was an association between the presence of limescale in water and direct culture for free-living amoebae, suggesting that scale provides a favourable microenvironment for amoebae. Acanthamoebae were also found in dust from around one washbasin. Nineteen of 50 CL cases, 12/122 CL care rinsing solutions, and 59/100 cold water taps yielded Gram negative bacteria which could be ingested by amoebae. It is concluded from this study that CLs should not be washed in first drawn tank-fed cold water, especially if limescale is present, and that soft CLs should be rinsed in manufactured single-use, sterile solutions. Rigid CL and CL cases should only be washed with boiled tap water (preferably hot), or single-use sterile solutions, and stored dry to prevent multiplication of amoebae and Gram negative bacteria. PMID- 1627514 TI - Biometry of the crystalline lens in late onset diabetes: the importance of diabetic type. AB - Lenticular and anterior chamber biometry were studied in non-cataractous eyes by means of Scheimpflug photography and digital image analysis. The study population consisted of 91 late onset diabetic subjects and 115 non-diabetic controls. Anteroposterior axial lens thickness, cortical thickness, nuclear thickness, anterior clear zone thickness, anterior chamber depth, and anterior and posterior lenticular curvatures were assessed. Age played an important role in determining lens biometry in all subjects, and small but significant differences were found between late onset diabetics and non-diabetics. In the late onset diabetic subgroup, apart from age, diabetic retinopathy was the only significant parameter found which determined lens biometry. These biometric findings in late onset diabetes are in marked contrast to the large overall effect of diabetes and the powerful effect of diabetic duration which we previously reported in early onset diabetes. Further analysis of the data from our previous study has been provided, which clearly demonstrates differences between the impact of early and late onset diabetes on the biometry of the anterior ocular segment. PMID- 1627515 TI - Nystagmus in infancy. PMID- 1627516 TI - Primary malignant ectomesenchymoma of the orbit. AB - Malignant ectomesenchymoma (MEM) is a rare soft tissue tumour believed to arise from a pluripotential migratory neural crest cell and composed of both a mesenchymal element (most often rhabdomyosarcoma) and a neuroectodermal element (often neuroblastoma). Reported sites of origin are the abdomen, perineum or scrotum, the extremities, the middle ear, nasopharynx, face, and neck. We report the first case of an orbital MEM, with a review of the 17 cases previously reported from other sites. PMID- 1627517 TI - Disc edge veins of Kraupa: rare exit anomalies of the retinal vein. AB - Disc edge veins of Kraupa are anomalies of the retinal venous system in which blood flows from the retina through a single venous trunk at or near the edge of the disc instead of at its centre. We report two examples of patients with these anomalies and illustrate the appearance of the anomalies with fundus photographs and a fluorescein angiogram. In one patient the retinal vein exited the eye through the sclera at the margin of the optic disc; in the other it disappeared into the disc tissue near the disc margin. PMID- 1627518 TI - Recurrent malignant melanoma of the corneal stroma: a case of 'black cornea'. AB - A 39-year-old Caucasian woman with a history of recurrent conjunctival melanoma of her right eye developed an intrastromal heavily pigmented malignant melanoma, which involved the whole corneal diameter. The patient was treated by corneoscleral lamellar keratoplasty and there has been no evidence of recurrent neoplasm during 4 years of follow-up. This apparently unique presentation of malignant melanoma of the cornea is illustrated and the differential diagnosis of corneal pigmentation is discussed. PMID- 1627519 TI - Ocular leprosy. PMID- 1627520 TI - Use of a blue filter in visual field analysis. PMID- 1627521 TI - A comparison between the old Transcend and the new Transcend series 2000 bracket. AB - The shear/peel and tensile/peel bond strengths of the original Transcend and the new Transcend series 2000 bracket were determined using two different light-cured composites, Prismafil (high filler) and Heliosit (low filler). Predominant sites of failure were recorded for each bracket with each cement in each mode of testing. Transcend series 2000 produced higher bond strengths than Transcend in shear/peel, but were significantly weaker in tensile/peel testing. Heliosit generally produced higher bond strengths than Prismafil. Enamel fractures were observed with Transcend in both modes of testing when bonded with Heliosit, but not with Transcend series 2000 when bonded with Heliosit. The new Transcend series 2000 brackets should only be removed in tensile/peel mode as suggested by the manufacturers, due to their very high bond strengths in shear. PMID- 1627522 TI - Functional appliances and arch width. AB - A retrospective study was undertaken using treated functional appliance cases. The groups involved 27 Andresen, 19 Bionator, and 23 Frankel cases. The reflex metrograph was used to measure arch width from study models at the start of treatment, end of treatment including retention, and at least 1 year post treatment. The effects of each appliance on arch width are compared during and after treatment. PMID- 1627523 TI - A modification to the incisor classification of malocclusion. AB - During the study of two-hundred orthodontic cases under treatment in the General Dental Service, four clinicians showed only moderate agreement using the British Standard Classification of Incisor Malocclusion. Cohen's Kappa statistic was used to measure the inter-examiner agreement. The 35 cases in which there was high disagreement between the examiners were scrutinized to determine the source of this disagreement. Following discussion, revised definitions were produced which included the introduction of a Class II-intermediate group. After an interval of 2 months these 35 cases were reclassified using the new definitions. Increased inter-examiner agreement was found. Four examiners (three of whom were common to the original study) then used the modified classification to describe the incisal relationship of 100 cases referred for treatment at Bristol Dental Hospital. The inter-examiner and the intra-examiner agreement were both found to be good. It is recommended that the Incisor Classification of Malocclusion be extended to include a Class II-intermediate group. PMID- 1627524 TI - Different techniques of residual composite removal following debonding--time taken and surface enamel appearance. AB - Four different methods of in vitro residual composite removal following debonding performed by two different operators (an orthodontist and a hygienist) were assessed for enamel surface damage (using scanning electron microscopy) and the time involved. There was no difference in the quality of enamel surface appearance between the two operators, regardless of the method used for composite removal. There was a statistically significant difference (P less than 0.05) for the time taken for composite removal between the two operators using a tungsten carbide bur method only. It is suggested that an expanded duties auxiliary with the practical skills of the hygienist would be able to remove residual composite debris and produce a satisfactory polished enamel surface using tungsten carbide burs and aluminium oxide polishing discs, thus becoming a safe and cost-effective member of the orthodontic team. PMID- 1627525 TI - Indelible bond location marks: an avoidable aesthetic hazard. AB - An increasingly popular method of aiding the precise placement of bonded brackets is to identify the long axis and centre of the crown with small pencil marks. A case is reported where marks placed with a soft pencil in the centre of the etched enamel have led to the inclusion of pigment deep in the enamel surface which has proved impossible to remove. PMID- 1627526 TI - The orthodontic/restorative interface. Restorative procedures to aid orthodontic treatment. AB - Restorative procedures which complement orthodontic treatment and which may be carried out by the orthodontist are summarized. The importance of planning, with the restorative requirements in mind and the maintenance of prepared space (individual tooth or abutment positions) in all three planes of space during the period of retention, is described. The importance of liaison regarding the timing of the placement of the definitive restoration, if it is to be carried out by another dental surgeon, is stressed. PMID- 1627527 TI - Part-time teachers in orthodontics. An Association of University Teachers of Orthodontics (AUTO) report. PMID- 1627528 TI - Recycling bands and brackets. AB - Orthodontists have a wide choice of companies offering a comprehensive recycling service at competitive prices. Careful debonding procedures should be used before sending bands and brackets for recycling. None of the companies make a charge for recycling damaged brackets, and some companies have established advanced systems of quality control. PMID- 1627529 TI - GDC's proposals on specialist registration. PMID- 1627530 TI - Research in the field of enamel demineralization and the implications that this has for orthodontic practice. PMID- 1627531 TI - The Barry Project--a cephalometric assessment of treatment change in a consecutive sample of malocclusion. AB - This is the last of a three-part series examining the results of orthodontic treatment in a consecutive sample of malocclusion from a Welsh town. The cephalometric changes are compared for the different treatment regimes which were employed. Where the variables being examined were common to both radiographs and study cast records the treatment changes observed for the regimes were similar. Only limited 'skeletal' change, interpreted as a change in a few cephalometric measurements, was found to occur during treatment. Perhaps of most interest was the consistent reduction of 'A' point in the full fixed appliance group. PMID- 1627532 TI - The prevalence and severity of malocclusion and the need for orthodontic treatment in 9-, 12-, and 15-year-old Glasgow schoolchildren. AB - An epidemiological investigation involving 765 Glasgow schoolchildren aged nine, twelve, and fifteen years was undertaken to assess the severity of malocclusion, the need for orthodontic treatment, and the proportion of children in each age group who had previously received treatment. An index termed the Malocclusion Severity Index (MSI) was developed to establish objectively the severity of malocclusion in each individual. Fifty sets of orthodontic study models and six orthodontists assessed the reproducibility and validity of the index. Although there was a significant reduction in the proportion of children in need of orthodontic treatment between 9 and 15 years of age, a considerable number were still in need of treatment; crowding of their dentitions being responsible for the majority of the treatment requirement. The MSI was found to be as precise and valid as previously developed occlusal indices, for estimating the treatment needs of sample populations. PMID- 1627533 TI - Three-dimensional evaluation of dentoskeletal changes after posterior cross-bite correction by quad-helix or removable appliances. AB - The aim of the study was to evaluate in a three-dimensional manner the dentoskeletal changes after slow maxillary expansion. The sample consisted of 34 children with a unilateral, symmetrical posterior cross-bite. Half of the children were treated with a quad-helix and the rest with a removable appliance. Assessment of the changes was made with study casts, and frontal and lateral cephalograms, before treatment, at the end of the expansion, after a retention period of 3 months, and after a post-retention period of 3 months. The results showed that sufficient expansion of the dental arches took place in both groups. The expansion expressed in the molar region in the quad-helix group was mostly due to buccal translation of the teeth and in the removable appliance group due to buccal tipping. The quad-helix group showed somewhat greater basal expansion than the removable appliance group, though the basal expansion in both groups was rather small. A tendency towards an increase of the NL/ML angle characterized the removable appliance group, but the opposite pattern was present in the quad-helix group. PMID- 1627534 TI - Immunoglobulin and HLA-DP genes contribute to the susceptibility to juvenile dermatitis herpetiformis. AB - HLA-DQ genes and gluten diet are the main factors involved in the pathogenesis of Dermatitis Herpetiformis (DH), as well as Coeliac Disease (CD). However other genetic factors are probably relevant, since about 10% of the patients with DH and CD lack the DQA1*0501/B1*0201 heterodimer while the majority of individuals presenting this genotype and also being exposed to gluten diets did not suffer from these diseases. To evaluate the role of other genes, 36 Northern Italian children with DH were analysed for DNA polymorphisms at HLA-DP and immunoglobulin (Ig) heavy chain loci. DPA1*0201 and DPB1*1301 frequencies were higher in patients than in controls (Pc = 0.0357 and Pc = 0.0273). With respect to immunoglobulin heavy chain restriction fragment length polymorphisms (RFLP), the 4.6 kb SacI RFLP at the switch alpha 2 gene was more frequent in patients (0.13) than in controls (0.019; Pc = 0.036). Moreover, rare alleles or duplications in the switch regions occurred more frequently in the patients than in the controls. These results support the hypothesis of a multifactorial inheritance of DH, the HLA and Ig constant heavy chain genes being some of the loci contributing to the susceptibility. In accordance with previous CD studies, these data also confirm that DP subregion is probably involved in the pathogenesis of DH. PMID- 1627535 TI - Damage in B2m genes and DNA methylation of H-2 genes are involved in loss of expression of class I MHC products on the membrane of LR.4, a cell line derivative of the T-cell lymphoma L5178Y. AB - We have isolated an H-2 deficient cell line (LR.4) from the T-cell lymphoma L5178Y which grew without restrictions in the peritoneal cavity of different inbred strains of mice. The use of polyclonal anti-H-2 antiserum and complement indicated that LR.4 cells did not express class I determinants on the cell membrane. Southern blots of genomic DNA of LR.4 cells showed that B2m genes were severely damaged and that class I H-2 genes were extensively methylated. Consequently, LR.4 cells failed to transcribe mRNAs for both B2m and class I H-2 genes. On the other hand, specific immunity to LR.4 was demonstrated in C57BL/6J mice since, in subsequent challenges with either LR.4 or EL4.4, LR.4 did not grow, whereas EL4.4 grew and killed the mice. In C57BL/6J mice, rejection of LR.4 was accompanied by the production of cytotoxic antibodies. The immune response induced in C57BL/6J mice was determined by non-H-2 antigenic determinants in LR.4 cells. PMID- 1627536 TI - Detailed mapping of the Rfv-1 gene that influences spontaneous recovery from Friend retrovirus-induced leukaemia. AB - Using H-2 recombinant and mutant mice, the Rfv-1 gene influencing spontaneous recovery from Friend retrovirus (FV)-induced leukaemia was mapped in the D locus. Two Db alleles were required for full recovery, and a single Dd transgene did not convey increased susceptibility to FV in the presence of homozygous Db/b genotype. The results suggest that an increase in the expression of Db may lead to more effective stimulation of FV-specific CTL. PMID- 1627537 TI - Nomenclature for factors of the HLA system, 1991. PMID- 1627538 TI - Detection of structural changes upon S1-to-S2 transition in the oxygen-evolving manganese cluster in photosystem II by light-induced Fourier transform infrared difference spectroscopy. AB - The light-induced Fourier transform infrared (FT-IR) difference spectrum between the S1 and S2 states of the O2-evolving photosystem II (PSII) was obtained for the first time. Detection of an S2/S1 difference spectrum virtually free from contributions by the acceptor-side signals was achieved by employing an exogenous electron acceptor, potassium ferricyanide, to trypsin-treated PSII membranes and using one-flash excitation at 250 K. A synthetic difference spectrum obtained by adding this S2/S1 spectrum to the QA-/QA spectrum measured with Mn-depleted PSII was almost identical with the difference spectrum of the S2QA-/S1QA charge separation measured with untreated PSII. This successful simulation verifies the correctness of the S2/S1 spectrum thus obtained. The observed S2/S1 spectrum reflects the structural changes within the water-oxidizing Mn cluster upon the S1 to-S2 transition, most probably changes in vibrational modes of ligands coordinating to the Mn ion(s) that is (are) oxidized upon the S2 formation and/or changes in protein conformation. The present results demonstrate that FT-IR difference spectroscopy is a promising method to investigate the structure of the intermediates of the Mn cluster involved in photosynthetic water oxidation. PMID- 1627539 TI - Purine nucleoside phosphorylase. Inosine hydrolysis, tight binding of the hypoxanthine intermediate, and third-the-sites reactivity. AB - Purine nucleoside phosphorylase from calf spleen is a trimer which catalyzes the hydrolysis of inosine to hypoxanthine and ribose in the absence of inorganic phosphate. The reaction occurs with a turnover number of 1.3 x 10(-4) s-1 per catalytic site. Hydrolysis of enzyme-bound inosine occurs at a rate of 2.0 x 10( 3) s-1 to form a stable enzyme-hypoxanthine complex and free ribose. The enzyme hydrolyzes guanosine; however, a tightly-bound guanine complex could not be isolated. The complex with hypoxanthine is stable to gel filtration but can be dissociated by acid, base, or mild denaturing agents. Following gel filtration, the E.hypoxanthine complex dissociates at a rate of 1.9 x 10(-6) s-1 at 4 degrees C and 1.3 x 10(-4) s-1 at 30 degrees C. The dissociation constant for the tightly bound complex of enzyme-hypoxanthine is estimated to be 1.3 x 10(-12) M at 30 degrees C on the basis of the dissociation rate. The stoichiometry of the reaction is 1 mol of hypoxanthine bound per trimer. The reaction is reversible since the same complex can be formed from enzyme and hypoxanthine. Addition of ribose 1-phosphate to the complex results in the formation of inosine without release of hypoxanthine. Thus, the complex is catalytically competent. Inorganic phosphate or arsenate prevents formation of the tightly-bound E.hypoxanthine complex from inosine or hypoxanthine. Direct binding studies with hypoxanthine in the presence of phosphate result in 3 mol of hypoxanthine bound per trimer with a dissociation constant of 1.6 microM. In the absence of phosphate, three hypoxanthines are bound, but higher hypoxanthine concentrations cause the release of two of the hypoxanthines with an apparent inhibition constant of 130 microM. The results establish that enzymatic contacts with the nucleoside alone are sufficient to destabilize the N-glycosidic bond. In the absence of phosphate, water attacks slowly, causing net hydrolysis. The hydrolytic reaction leaves hypoxanthine stranded at the catalytic site, tightly bound to the enzyme with a conformation related to the transition state. In the phosphorolysis reaction, ribose 1-phosphate causes relaxation of this conformation and rapid release of hypoxanthine. PMID- 1627540 TI - Three-dimensional structure of the apo form of the N-terminal EGF-like module of blood coagulation factor X as determined by NMR spectroscopy and simulated folding. AB - The three-dimensional structure of a 42-residue fragment containing the N terminal EGF-like module of blood coagulation factor X was determined by means of 2D NMR spectroscopy and computer simulation. The spectroscopic data consisted of 370 NOE distances and 27 dihedral angle constraints. These were used to generate peptide conformations by molecular dynamics simulation. The simulations used a novel functional form for the constraint potentials and were performed with two time steps to ensure rapid execution. Apart from preliminary runs to aid assignment of NOEs, 60 runs resulted in 13 accepted structures, which have two antiparallel beta sheets, no alpha helices, and five tight turns. There is no hydrophobic cluster. The root mean square deviation for the backbone of the 13 conformations is 0.65 +/- 0.11 A against their mean conformation. About half of the side chains have well-defined structure. The overall conformation is similar to that of murine EGF. PMID- 1627541 TI - Surface binding kinetics of prothrombin fragment 1 on planar membranes measured by total internal reflection fluorescence microscopy. AB - Total internal reflection fluorescence microscopy (TIRFM) has been employed to investigate the Ca(2+)-dependent membrane-binding characteristics of fluorescein labeled bovine prothrombin-fragment 1 (F-BF1). Light scattering measurements demonstrated that F-BF1 bound to small unilamellar phosphatidylserine/phosphatidylcholine (25/75, mol/mol) vesicles with an apparent dissociation constant (1.5 +/- 0.2 microM) similar to that of unlabeled protein (1.1 +/- 0.1 microM). Negatively charged supported planar membranes were constructed by fusing small unilamellar vesicles at quartz surfaces. TIRFM measurements under equilibrium conditions showed that F-BF1 bound to planar membranes with an apparent dissociation constant (0.9 +/- 0.2 microM) approximately equal to that on vesicles. Total internal reflection/fluorescence photobleaching recovery (TIR/FPR) curves for F-BF1 on 25 mol% PS planar surfaces were diffusion-influenced at F-BF1 solution concentrations less than or equal to 5 microM. Fluorescence recovery rates from samples of high F-BF1 concentrations were slowed by increasing the solution viscosity with glycerol, thus providing further support for a diffusion-limited effect at low F-BF1 concentrations. Analysis of the reaction-limited fluorescence recovery curves at F-BF1 solution concentrations greater than or equal to 10 microM gave average association and dissociation kinetic rates of approximately 10(5) M-1 s-1 and approximately 0.1 s 1, respectively. Kinetic association rates increased significantly with increasing PS, whereas kinetic dissociation rates increased only slightly. Fluorescence recovery curves were nonmonoexponential; possible mechanisms for this behavior are described. PMID- 1627542 TI - Heparin binding to human plasma low-density lipoproteins: dependence on heparin sulfation degree and chain length. AB - Binding between low-density lipoproteins (LDL) and fluorescein-labeled heparin was studied quantitatively with a modified form of a published procedure [Cardin, A. D., Randall, C. I., Hirose, N., & Jackson, R. L. (1987) Biochemistry 26, 5513 5518], using fluorescence anisotropy titrations. Assumption of binding site equivalence satisfactorily interpreted experimental data. Accordingly, the apparent total capacity, n, and the average dissociation constant, Kd, were estimated as n approximately 24 disaccharides per LDL particle and Kd approximately 4 microM in 0.05 M HEPES/0.1 M NaCl, pH 7.4, 22 degrees C. Competition experiments with unlabeled heparins were exploited for the quantitative study of Kd as a function of heparin chain length and sulfation degree (ns = sulfate groups per disaccharide). The former parameter was investigated with a series of bovine lung heparin fractions with Mw ranging from 1,800 to 21,000 and constant sulfation degree (ns = 2.8 +/- 0.1). A series of physically fractionated or chemically modified heparins having 1.2 less than ns less than 3.5 were used to explore the dependence on sulfation degree. LDL affinity was found to increase with increasing both ns and Mw: an empirical Mw 1.6 dependence represented very well the chain length data set; a linear dependence was observed for log Kd as a function of ns, after appropriate allowance was made for chain length differences among samples. This regularity confirmed that LDL-heparin binding is mainly driven by electrostatic forces.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627543 TI - Extensive comparison of the substrate preferences of two subtilisins as determined with peptide substrates which are based on the principle of intramolecular quenching. AB - Subtilisins are serine endopeptidases with an extended binding cleft comprising at least eight binding subsites. Interestingly, subsites distant from the scissile bond play a dominant role in determining the specificity of the enzymes. The development of internally quenched fluorogenic substrates, which allow polypeptides of more than 11 amino acids to be inserted between the donor and the acceptor, has rendered it possible to perform a highly systematic mapping of the individual subsites of the active sites of subtilisin BPN' from Bacillus amyloliquefaciens and Savinase from Bacillus lentus. For each enzyme, the eight positions S5-S'3 were characterized by determination of kcat/KM values for the hydrolysis of substrates in which the amino acids were systematically varied. The results emphasize that in both subtilisin BPN' and Savinase interactions between substrate and S4 and S1 are very important. However, it is apparent that interactions between other subsites and the substrate exert a significant influence on the substrate preference. The results are rationalized on the basis of the structural data available for the two enzymes. PMID- 1627544 TI - Inactivation of dimeric D-amino acid transaminase by a normal substrate through formation of an unproductive coenzyme adduct in one subunit. AB - D-amino acid transaminase, which contains pyridoxal 5'-phosphate (vitamin B6) as coenzyme, catalyzes the formation of D-alanine and D-glutamate from their corresponding alpha-keto acids; these D-amino acids are required for bacterial cell wall biosynthesis. Under conditions usually used for kinetic assay of enzyme activity, i.e., short incubation times with dilute enzyme concentrations, D alanine behaves as one of the best substrates. However, the enzyme slowly loses activity over a period of hours when exposed to substrates, intermediates, and products at equilibrium. The rate of inactivation is dependent on enzyme concentration but independent of substrate concentration greater than Km values. Continuous removal of the product pyruvate by enzymic reduction precludes the establishment of equilibrium and prevents inactivation. The formation of small but detectable amounts of a quinonoid intermediate absorbing at 493 nm is proportional to inactivation. Studies with [14C]-D-alanine labeled on different carbon atoms indicate that the alpha-carboxyl group of the substrate is absent in the inactive enzyme; such decarboxylation is not a usual function of this enzyme. The inactive transaminase contains 1.1 mol of [14C]-D-alanine-derived adduct per mole of dimeric enzyme; this finding is consistent with the 50% reduction in the fluorescence intensity at 390 nm (due to the PMP form of the coenzyme) for the inactive enzyme. Thus, inactivation of one subunit of the dimeric enzyme renders the entire molecule inactive. Inactivation may occur when a coenzyme intermediate, perhaps the ketimine, is slowly decarboxylated and then undergoes a conformational change from its catalytically competent location.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627545 TI - Complete replacement set of amino acids at the C-terminus of thymidylate synthase: quantitative structure-activity relationship of mutants of an enzyme. AB - The C-terminal residue of thymidylate synthase (TS) is highly conserved and has been implicated in cofactor binding, catalysis, and a conformational change. The codon for the C-terminal valine of Lactobacillus casei TS has been replaced with those for 19 other amino acids and the amber stop codon. Fourteen of the resulting mutant proteins were active by genetic complementation using a Thy- strain of Escherichia coli, and 18 mutants were active by in vitro assay. Only the aspartate and amber mutations had undetectable activity. All of the mutants were expressed at high levels (5-30% of soluble protein) and were purified by phosphocellulose chromatography. In general, the alterations at position 316 led to little effect on the Km for dUMP, an increase in Km for the folate cofactor, and a decrease in kcat. The observations show that TS can tolerate the substitution of most amino acids for valine at the C-terminus without a complete loss of activity, that hydrophobic substitutions are preferred, and that the C terminal side chain is involved in both cofactor binding and catalysis. There was an excellent correlation between log kcat and hydrophobicity of the side chain at position 316 and an inverse correlation between log Km and the hydrophobicity of this residue. Kinetic parameters of the cofactor-independent TS-catalyzed dehalogenation of BrdUMP showed no variation with the side chain at position 316. In context of the structure of TS, it is proposed that binding of the cofactor triggers a conformational change in which the C-terminal side chain undergoes hydrophobic interactions that stabilize a rate-limiting transition state of the TS reaction. PMID- 1627546 TI - Thymidylate synthase with a C-terminal deletion catalyzes partial reactions but is unable to catalyze thymidylate formation. AB - The V316Am mutant of Lactobacillus casei thymidylate synthase has a single amino acid deletion at the C-terminus which abolishes catalysis of dTMP formation. However, V316Am catalyzes two partial reactions which require covalent catalysis: a CH2H4folate-dependent exchange of the 5-hydrogen of dUMP for protons in water and a thiol-dependent dehalogenation of 5-bromo- and 5-iodo-dUMP. These reactions proceed with kcat and Km values similar to those of the wild-type TS-catalyzed reactions. dUMP, dTMP, and FdUMP are competitive inhibitors of the debromination reaction with Ki values similar to those obtained with wild-type enzyme. These results show that removal of the terminal valine does not alter the ability of the enzyme to bind to or form covalent bonds with nucleotide ligands. V316Am also forms a covalent ternary complex with FdUMP and CH2H4folate. However, the affinity of the TS-FdUMP complex for the cofactor is reduced, and the rate of covalent ternary complex formation and its stability are significantly lower than with wild-type TS. These results allow us to place the major defects of the mutation on steps that occur subsequent to initial CH2H4folate binding. PMID- 1627547 TI - Basis for the anomalous effect of competitive inhibitors on the kinetics of hydrolysis of short-chain phosphatidylcholines by phospholipase A2. AB - The effect of four specific competitive inhibitors on the kinetics of hydrolysis of short-chain diacyl-sn-glycero-3-phosphocholines below their critical micelle concentrations was examined. The kinetics of hydrolysis of short-chain substrates dispersed as solitary monomers were generally consistent with the classical Michaelis-Menten formalism; i.e., hydrolysis began without any latency period, the steady-state rate was observed at higher substrate concentrations, the steady state initial rate showed a linear dependence on the enzyme concentration, and the hyperbolic dependence of the initial rate on the substrate concentration could be described in terms of KM and Vmax parameters. The competitive nature of the inhibitors used in this study has been established by a variety of techniques, and the equilibrium dissociation constants for the inhibitors bound to the enzyme were measured by the protection method [Jain et al. (1991) Biochemistry 30, 7306-7317]. The kinetics of hydrolysis in the presence of competitive inhibitors could be described by a single dissociation constant. However, the value of the dissociation constant obtained under the kinetic conditions was comparable to that obtained by the protection method for the inhibitor-enzyme complex bound to a neutral diluent, rather than to the value of the dissociation constant obtained with solitary monomeric inhibitors and the enzyme in the aqueous phase. Spectroscopic methods showed that the effectively lower dissociation constant of an inhibitor bound to PLA2 at the interface is due to the stabilization of the enzyme-inhibitor complex by interaction with other amphiphiles present in the reaction mixture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627549 TI - Isomerization of (R)- and (S)-glutathiolactaldehydes by glyoxalase I: the case for dichotomous stereochemical behavior in a single active site. AB - The ability of glyoxalase I to isomerize both diastereomeric thiohemiacetals formed between glutathione and alpha-ketoaldehydes has been probed with stereochemically "locked" substrate analogues. Both (R)- and (S) glutathiolactaldehyde (5 and 5') were unambiguously synthesized by employing the Sharpless epoxidation procedure as a key step. In the presence of human erythrocyte glyoxalase I, high-field 1H NMR analysis reveals that the R and S isomers (approximately 20 mM) are both converted to glutathiohydroxyacetone at rates of 0.8 and 0.4 s-1, respectively. This reaction is characterized by a nonstereospecific proton abstraction followed by a partially shielded proton transfer to the si face of the cis-enediol intermediate. Glyoxalase I catalyzes the exchange of the pro-S proton of glutathiohydroxyacetone with solvent deuterium. Glutathiohydroxyacetone was found to be a good competitive inhibitor of the normal glyoxalase I reaction (KI = 1.46 mM), suggesting that the slow processing rate of these compounds with respect to the normal thiohemiacetals is not due to poor binding. The results are consistent with a nonstereospecific proton abstraction and a stereospecific reprotonation at contiguous substrate carbons. PMID- 1627548 TI - Role of phospholipids in reconstituted cytochrome P450 3A form and mechanism of their activation of catalytic activity. AB - Cytochrome P-450 coded for by the 3A gene family requires specific conditions in a reconstituted system, if its catalytic activity is to be efficient. We investigated the mechanism of activation of the catalytic activity of cytochrome P450 3A by phospholipids. Rat P450 PB-1 (3A2), human P450NF (3A4), and rabbit P450 3c (3A6) were used. They had low activity in a reconstituted system (system I) with dilauroylphosphatidylcholine (DLPC) but had high activity with a mixture of phospholipids (DLPC, dioleoylphosphatidylcholine, and phosphatidylserine) and sodium cholate (system II). P450 3A forms are cationic (having a high content of lysine residues) and needed the anionic phospholipid phosphatidylserine to have sufficient activity. Double-reciprocal plots of the metabolic rate of cytochrome P-450 versus the concentration of NADPH-cytochrome P-450 reductase showed that cytochrome P-450 and the reductase interacted more in system II than in system I. P450 PB-1 did not absorb at 450 nm in the presence of reductase, CO, DLPC, and NADPH, although other cytochrome P-450s absorbed at around 450 nm in such a mixture. However, P450 PB-1 was reduced in the presence of the phospholipid mixture and sodium cholate instead of DLPC. These results suggested that the stimulation of catalytic activity by phospholipids involved increased interaction between cytochrome P-450 and the reductase. Studies of proteolytic digestion and chemical cross-linking in systems I and II showed that a P450 3A form needed disaggregation of cytochrome P-450 and/or the reductase, not the formation of an aggregated complex necessary for the catalytic activity of other cytochrome P 450s. PMID- 1627550 TI - Structure of the human pancreatic cholesterol esterase gene. AB - The gene for human pancreatic cholesterol esterase consists of 11 exons and 10 introns and is 9.2 kb in length. The last and longest exon (841 nucleotides) is unique to the human gene. Functional amino acids are encoded on separate exons. The leader sequence is encoded by a single exon which carries two additional N terminal amino acids of the mature functional protein. A positive TATA element is identified 43 nucleotides from the start codon. Pulse-field gel electrophoresis and hybridization with various cDNA probes and direct sequence data revealed the existence of a CEase-like gene. Partial sequence analysis of this gene from a human cosmid library and human genomic DNA showed a premature stop signal in exon 10, shortly after the codon for the active-site histidine. Both the functional gene and the CEase-like gene have a polyadenylation signal in the 3'-untranslated region. Thus, the complex gene structure for this intestinally active enzyme may provide in part a potential molecular explanation for the well-known heterogeneity of the intestinal absorption of cholesterol. PMID- 1627551 TI - EcoRV restriction endonuclease: communication between catalytic metal ions and DNA recognition. AB - In the absence of magnesium ions, the EcoRV restriction endonuclease binds all DNA sequences with equal affinity but cannot cleave DNA. In the presence of Mg2+, the EcoRV endonuclease cleaves DNA at one particular sequence, GATATC, at least a million times more readily than any other sequence. To elucidate the role of the metal ion, the reactions of the EcoRV restriction enzyme were studied in the presence of MnCl2 instead of MgCl2. The reaction at the EcoRV recognition site was slower with Mn2+. This was caused partly by reduced rates for phosphodiester hydrolysis but also by the translocation of the enzyme along the DNA after cleaving it in one strand. In contrast, alternative sites that differ from the recognition site by one base pair were cleaved faster in the presence of Mn2+ relative to Mg2+. When located at an alternative site on the DNA, the EcoRV enzyme bound Mn2+ ions readily but had a very low affinity for Mg2+. The EcoRV nuclease is thus restrained from cleaving DNA at alternate sites in the presence of Mg2+, but the restraint fails to operate with Mn2+. A discrimination factor, which measures the ratio of the activity of the EcoRV nuclease at its recognition site over that at an alternative site, had values of 3 x 10(5) in MgCl2 and 6 in MnCl2. PMID- 1627552 TI - EcoRV restriction endonuclease: communication between DNA recognition and catalysis. AB - A genetic system was constructed for the mutagenesis of the EcoRV restriction endonuclease and for the overproduction of mutant proteins. The system was used to make two mutants of EcoRV, with Ala in place of either Asn185 or Asn188. In the crystal structure of the EcoRV-DNA complex, both Asn185 and Asn188 contact the DNA within the EcoRV recognition sequence. But neither mutation affected the ability of the protein to bind to DNA. In the absence of metal ion cofactors, the mutants bound DNA with almost the same affinity as that of the wild-type enzyme. In the presence of Mg2+, both mutants retained the ability to cleave DNA specifically at the EcoRV recognition sequence, but their activities were severely depressed relative to that of the wild-type. In contrast, with Mn2+ as the cofactor, the mutant enzymes cleaved the EcoRV recognition site with activities that were close to that of the wild-type. When bound to DNA at the EcoRV recognition site, the mutant proteins bound Mn2+ ions readily, but they had much lower affinities for Mg2+ ions than the wild-type enzyme. This was the reason for their low activities with Mg2+ as the cofactor. The arrangement of the DNA recognition functions, at one location in the EcoRV restriction enzyme, are therefore responsible for organizing the catalytic functions at a separate location in the protein. PMID- 1627553 TI - Characterization of the alpha and beta subunits of casein kinase 2 by far-UV CD spectroscopy. AB - Although Chou-Fasman calculations of the secondary structure of recombinant casein kinase 2 subunits alpha and beta suggest they have a similar overall conformation, circular dichroism (CD) studies show that substantial differences in the conformation of the two subunits exist. In addition, comparison of the far UV CD spectrum of reconstituted CK-2 with the spectra of the subunits indicates that conformational changes occur in the backbone region upon association. Such changes may explain the increased enzyme activity of the holoenzyme relative to that of the alpha subunit itself. In contrast, no changes in the far-UV CD spectrum of the alpha subunit are observed in the presence of casein or the synthetic decapeptide substrate RRRDDDSDDD. Furthermore, the alpha-helical structure of the alpha subunit (but not the beta subunit) can be increased in the presence of stoichiometric amounts of heparin, presumably by its binding to the polylysine stretch at amino acid positions 74-77. Heat denaturation experiments (25-90 degrees C) support the notion that heparin may provide a local protective function. A similar but much larger effect was also observed in the presence of the beta subunit only, which supports previous suggestions of a protective function for this subunit. These results indicate that the protection provided by the beta subunit and the increased enzyme activity of the holoenzyme may arise, in part, from a stabilization of the conformation of the enzyme complex and an increase in alpha-helical content. PMID- 1627554 TI - Fusion of phospholipid vesicles induced by an amphiphilic model peptide: close correlation between fusogenicity and hydrophobicity of the peptide in an alpha helix. AB - A model peptide with 51 amino acid residues consisting of tandem repeats of a Lys Lys-Leu-Leu sequence and a turn sequence of Asn-Pro-Gly at the center of the molecule has a random conformation at neutral pH but adopts an amphiphilic alpha helical form in the presence of various salts or nucleotides [Goto, Y., & Aimoto, S. (1991) J. Mol. Biol. 218, 387-396; Goto, Y., Okamura, N., & Aimoto, S. (1991) J. Biochem. (Tokyo) 109, 746-750]. The interaction of this model peptide with liposome membranes and the resulting alpha-helical conformational transition and membrane fusion as well as the effect of the nucleotide ATP on these events were examined at neutral pH. The peptide associated stoichiometrically with liposome membranes composed of phosphatidylserine (PS) and phosphatidylcholine (PC) in a molar ratio of 2:1, resulting in formation of an amphiphilic alpha-helix and induction of fusion of the liposomes. However, the final fusion level was not correlated with the amount of binding or the helix content and was found to increase on an increase in hydrophobicity of the peptide in the alpha-helical form by neutralization of its positive charges by the negative charges of PS. In contrast, in the presence of ATP, the peptide bound completely to the PS/PC membranes at a lower concentration of liposome and concomitantly induced membrane fusion, indicating that ATP cooperates with PS to neutralize the charges of the peptide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627555 TI - Autophosphorylation of skeletal muscle myosin light chain kinase. AB - Ca2+/calmodulin-dependent myosin light chain kinase phosphorylates the regulatory light chain of myosin. Rabbit skeletal muscle myosin light chain kinase also catalyzes a Ca2+/calmodulin-dependent autophosphorylation with a rapid rate of incorporation of 1 mol of 32P/mol of kinase and a slower rate of incorporation up to 1.52 mol of 32P/mol. Autophosphorylation was inhibited by a peptide substrate that has a low Km value for myosin light chain kinase. Autophosphorylation at both rates was concentration-independent, indicating an intramolecular mechanism. There were no significant changes in catalytic properties toward light chain and MgATP substrates or in calmodulin activation properties upon autophosphorylation. After digestion with V8 protease, phosphopeptides were purified and sequenced. Two phosphorylation sites were identified, Ser 160 and Ser 234, with the former associated with the rapid rate of phosphorylation. Both sites are located amino terminal of the catalytic domain. These results indicate that the extended "tail" region of the enzyme can fold into the active site of the kinase. PMID- 1627556 TI - Identification of the Ca(2+)-dependent calmodulin-binding region of chromogranin A. AB - Chromogranin A (CGA), the most abundant protein in bovine adrenal chromaffin granules, is a high-capacity, low-affinity Ca(2+)-binding protein found in most neuroendocrine cells, and binds calmodulin (CaM) in a Ca(2+)-dependent manner. The binding of chromogranin A to calmodulin was determined by measuring the intrinsic tryptophan fluorescence of chromogranin A in the presence and absence of Ca2+. Binding was specifically Ca(2+)-dependent; neither Mg2+ nor Mn2+ could substitute for Ca2+. Chelation of Ca2+ by EGTA completely eliminated the chromogranin A-calmodulin interaction. CaM binding was demonstrated by a synthetic CGA peptide representing residues 40-65. When the CGA peptide and CaM were mixed in the presence of 15 mM CaCl2, the intrinsic tryptophan fluorescence emission underwent a substantial blue-shift, shifting from 350 to 330 nm. Like the intact CGA, the peptide-CaM binding was specifically Ca(2+)-dependent, and neither Mg2+ nor Mn2+ could induce the binding. Calmodulin bound both to CGA and to the synthetic CGA peptide with a stoichiometry of one to one. The dissociation constants (Kd) determined by fluorometric titration were 13 nM for the peptide CaM binding and 17 nM for intact CGA-CaM binding. The Kd values are comparable to those (approximately 10(-9) M) of other CaM-binding proteins and peptides, demonstrating a tight binding of CaM by CGA. The CaM-binding CGA residues 40-65 are 100% conserved among all the sequenced CGAs in contrast to 50-60% conservation found in the entire sequence, implying essential roles of this region. PMID- 1627557 TI - Phosphatidylinositol inhibits microtubule assembly by binding to microtubule associated protein 2 at a single, specific, high-affinity site. AB - The effects of various anionic phospholipids on the in vitro assembly of MAP2/tubulin microtubules has been examined. We show that the potency to inhibit is related to the polarity of the phospholipids and that this is consistent with a mode of action involving the sequencing of microtubule-associated proteins (MAPs) by nonspecific electrostatic interactions. The inhibitory potency of phosphatidylinositol (PI) is, however, considerably larger than predicted by this model. The effects of PI on MAP2/tubulin microtubule assembly have therefore been examined in greater detail by preparing phosphatidylcholine (PC) liposomes doped with increasing amounts of PI. We show that when the PI is sufficiently dispersed by dilution with PC, it inhibits microtubule assembly by binding to MAP2 with an apparent stoichiometry, after correction for the bilamellar nature of the liposomes, of 1:1 mol.mol-1 PI:MAP2. Furthermore, we show that the Kd of this interaction is in the submicromolar range. PMID- 1627558 TI - Bacteriorhodopsin can be refolded from two independently stable transmembrane helices and the complementary five-helix fragment. AB - This paper describes experimental tests of the hypothesis that bacteriorhodopsin (BR) can fold by the association of independently stable transmembrane helices. Peptides containing the first and second helical segments of BR were chemically synthesized. These two peptides and the complementary five-helix fragment of BR were reconstituted in three separate populations of native-lipid vesicles which were then mixed and fused to allow the fragments to interact. After addition of retinal, absorption spectroscopy of the reconstituted BR and X-ray diffraction of two-dimensional crystals of this material showed that the native structure of BR was regenerated. The first two helices of BR can therefore be considered as independent folding domains, and covalent connections in the loops connecting the helices to each other and to the rest of the molecule are not essential for the appropriate association of the helices. PMID- 1627559 TI - The broad diversity of neutral and sialylated oligosaccharides derived from human salivary mucins. AB - Mucin glycopeptides were prepared from the salivary mucins of 20 healthy donors with blood group O. The carbohydrate chains of the high-molecular-weight mucins were released by alkaline borohydride treatment. Neutral and monosialylated oligosaccharide-alditols were purified by ion-exchange chromatography, gel filtration, and HPLC. The structures of the oligosaccharide-alditols were determined by high-resolution 1H-NMR spectroscopy in combination with fast atom bombardment mass spectrometry and methylation analysis. Thirty-seven oligosaccharide-alditols were characterized and illustrate the extreme diversity of the salivary mucins carbohydrate chains. This diversity might represent a mosaic of bacterial adhesion sites and be involved in the early events of the nonimmune defense of the oral cavity. Among these 37 oligosaccharide-alditols, 31 have not been previously described in human saliva and five of these are novel structures: [formula: see text] PMID- 1627560 TI - Cooperative binding of polyamines induces the Escherichia coli single-strand binding protein-DNA binding mode transitions. AB - The Escherichia coli single-strand binding (SSB) protein is an essential protein involved in DNA replication, recombination, and repair processes. The tetrameric protein binds to ss nucleic acids in a number of different binding modes in vitro. These modes differ in the number of nucleotides occluded per SSB tetramer and in the type and degree of cooperative complexes that are formed with ss DNA. Although it is not yet known whether only one or all of these modes function in vivo, based on the dramatically different properties of the SSB tetramer in these different ss DNA binding modes, it has been suggested that the different modes may function selectively in replication, recombination, and/or repair. The transitions between these different modes are very sensitive to solution conditions, including salt (concentration, as well as cation and anion type), pH, and temperature. We have examined the effects of multivalent cations, principally the polyamine spermine, on the SSB-ss poly(dT) binding mode transitions and find that the transition from the (SSB)35 to the (SSB)56 binding mode can be induced by micromolar concentrations of polyamines as well as the inorganic cation Co(NH3)6(3+). Furthermore, these multivalent cations, as well as Mg2+, induce the binding mode transition by binding cooperatively to the SSB-poly(dT) complexes. These observations are interesting in light of the fact that polyamines, such as spermidine, are part of the ionic environment in E. coli and hence these cations are likely to affect the distribution of SSB-ss DNA binding modes in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627561 TI - Interaction of thymosin beta 4 with muscle and platelet actin: implications for actin sequestration in resting platelets. AB - Quantitative measurements of the interactions of T beta 4 with muscle actin suggest that its only physiological role is monomer sequestration. T beta 4 forms a 1:1 complex with monomeric actin under physiological salt conditions. Its Kd for actin is not affected by calcium. T beta 4 binds only to actin monomers and not to filament ends or alongside the filament. T beta 4-actin complexes do not elongate actin filaments at either the barbed or the pointed end, and, unlike actobindin, T beta 4 does not specifically suppress the nucleation of polymerization. We assessed the fraction of monomeric actin that can be sequestered by T beta 4 in resting platelets. This was done on the basis of (a) its Kd of 0.4-0.7 microM for platelet actin, which had been prepared by a newly devised simpler method, and (b) the values for the concentrations of monomeric actin and of T beta 4 which we measured as 280 and 560 microM, respectively. Using the higher Kd value of 0.7 microM, the T beta 4-complexed actin is calculated to be between 70 and 240 microM, depending on the steady-state free G actin concentration. This may vary from 0.1 to 0.5 microM, the critical concentrations for uncapped and for fully barbed-end-capped actin filaments. If the Kd in the platelet is the same as in vitro, most of the sequestered actin would be bound to T beta 4 if more than 95% of the actin filaments are capped at their barbed ends in resting platelets. PMID- 1627562 TI - Identification of five sites of acetylation in alfalfa histone H4. AB - Radioactive acetylation in vivo of plant histone H4 of alfalfa, Arabidopsis, tobacco, and carrot revealed five distinct forms of radioactive, acetylated histone. In histone H4 of eukaryotes ranging from fungi to man, acetylation is restricted to four lysines (residues 5, 8, 12, and 16) possibly caused by a quantitative methylation of lysine-20. Chemical and proteolytic fragmentation of the amino terminally blocked alfalfa H4 protein, dynamically acetylated by radioactive acetate in vivo, allowed protein sequencing and identification of selected peptides. Peptide identification was facilitated by analyzing fully characterized calf histone H4 in parallel. Acetylation in vivo of alfalfa histone H4 was restricted to the lysines in the amino-terminal domain of the protein, residues 1-23. Lysine-20 was shown to be free of methylation, as in pea histone H4. This apparently makes lysine-20 accessible as a novel target for histone acetylation. The in vivo pattern of lysine acetylation (16 greater than 12 greater than 8 greater than or equal to 5 = 20) revealed a preference for lysines -16 and -12 without an apparent strict sequential specificity of acetylation. PMID- 1627563 TI - Isolation and sequence of a cDNA encoding porcine mitochondrial NADP-specific isocitrate dehydrogenase. AB - The cDNA for porcine mitochondrial NADP-specific isocitrate dehydrogenase was isolated from a lambda gt11 library using polymerase chain reaction. Translation of the DNA sequence gave a 413-residue amino acid sequence and a calculated molecular weight of 46,600 for the mature polypeptide. Previously determined peptide sequences for the amino terminus and for internal tryptic peptides were all contained within the translated sequence. The porcine protein was found to share 63% residue identity with yeast mitochondrial NADP-specific isocitrate dehydrogenase and to be immunoreactive with an antiserum against the yeast protein. Highly conserved regions include residues which have been implicated in substrate and cofactor binding in previous studies of the porcine enzyme. The two eucaryotic enzymes exhibit only minimal homology with the NADP-dependent isocitrate dehydrogenase from Escherichia coli, with the exception of a striking conservation of residues implicated in formation of the metal-isocitrate site of the procaryotic enzyme. PMID- 1627564 TI - Binding specificities of actinomycin D to non-self-complementary -XGCY tetranucleotide sequences. AB - Studies on the binding specificity of actinomycin D (ACTD) to tetranucleotide sequences of the form -XGCY- have been extended to include the non-self complementary sequences. ACTD binding characteristics are investigated by equilibrium, kinetic, and thermal denaturation for decameric duplexes d(ATA-XGCY ATA)-d(TAT-Y'GCX'-TAT), where X and Y are complementary to X' and Y', respectively, but not to each other. The results indicate that when X = G or Y = C, the oligomers exhibit significantly weaker ACTD binding affinities, smaller melting temperature increases upon drug binding, and faster SDS-induced ACTD dissociation rates than the other sequences. Estimated binding constants at 18.5 degrees C for decameric duplexes containing -AGCA-/-TGCT-, -AGCG-/-CGCT-, or CGCA-/-TGCG- are in the range of 4-9 microM-1, whereas for the ones containing GGCT-/-AGCC-, -GGCA-/-TGCC-, or -GGCG-/-CGCC- they range from 0.6 to 2 microM-1. In contrast to the characteristic SDS-induced ACTD dissociation times of 600-1000 s for the stronger binding sites, the sequences containing X = G or Y = C exhibit at least an order of magnitude faster dissociation kinetics. These observations are further supported by the induced CD results and fluorescence measurements with 7-amino-ACTD. The findings from these non-self-complementary -XGCY- tetranucleotide sequences are consistent with those found earlier for the self complementary counterparts, and they together clearly demonstrate that a base sequence alteration adjacent to the GC site can have a profound effect on the ACTD binding as well as dissociation characteristics, likely a consequence of subtle conformational alterations near the binding site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627565 TI - Hairpin and duplex forms of a self-complementary dodecamer, d-AGATCTAGATCT, and interaction of the duplex form with the peptide KGWGK: can a pentapeptide destabilize DNA? AB - Ordered forms of a synthetic dodecamer, d-AGATCTAGATCT, a direct repeat of the BglII recognition sequence, have been investigated using UV, CD, and fluorescence spectroscopy. Complex hairpin-duplex equilibria are manifest in UV thermal transitions, which are monophasic in the presence of very low or high NaCl concentrations but distinctly biphasic at intermediate ionic strengths. In 100 mM NaCl, the 1/Tm vs 1n C curve has a reasonable positive slope, which yields delta H and delta S for duplex formation as -66.2 kcal/mol and -190 cal/mol, respectively. Interaction of the dodecamer in duplex form with a tryptophan containing peptide, KGWGK, has also been investigated to test the "bookmark" hypothesis (Gabbay et al., 1976) under the uniform structural constraint of the oligonucleotide of defined sequence. CD spectra of the peptide (P), the oligonucleotide (N), and their mixtures at different P/N ratios show a dramatic change in peptide spectrum but little change in nucleic acid dichroism with peptide binding. The Tm of P-N complexes decreases with an increase in peptide binding and levels off at saturation binding of P/N = 2.0. The data are interpreted in terms of a groove-cum-intercalation mode of binding, where intercalation to the tryptophan side chain destabilizes the double helix. A Scatchard plot of the binding data is nonlinear, with best-fit values for an overall association constant K = 4.33 x 10(5) M-1, and the number of binding sites n = 3.23 when fitted to the site-exclusion model of binding. PMID- 1627566 TI - Co2+ as a shift reagent for 35Cl NMR of chloride with vesicles and cells. AB - Applications of high-resolution 35Cl NMR to the study of chloride in vivo and in vesicles have hitherto been limited by problems of NMR detectability and of resolving internal from external signals. We have characterized the effects of Co2+ on the 35Cl resonance of Cl- in solution and have shown that when added to suspensions of lipid vesicles, Co2+ shifts the 35Cl signal of the extravesicular Cl-, allowing clear resolution and quantitation of two peaks. We have assigned these signals to chloride inside and outside the vesicles. The spectra do not change over a 90-min period, demonstrating the stability of the vesicles in the presence of Co2+. This technique is shown to be applicable to red blood cell ghosts, where intravesicular and extravesicular chloride signals were separated and measured and chloride/sulfate exchange through the band 3 anion transport protein A was followed. In two plant species (an alga and a higher plant), an intracellular Cl- signal can be observed and resolved from the extracellular signal. The intracellular transportable chloride was found to be fully NMR visible (+/- 5%) in the algal cells. The high steady-state levels of Cl- seen in the alga were consistent with previous work using 36Cl- labeling on a related species [Doblinger, R., & Tromballa, H.W. (1982) Planta 156, 10-15]. Successive spectra acquired after adding Co2+ to Chlorella cells under deenergizing conditions allow us to follow the time course of movement of Cl- out of the cells. PMID- 1627567 TI - Use of a potential of mean force to analyze free energy contributions in protein folding. AB - A method for calculation of the free energy of residues as a function of residue burial is proposed. The method is based on the potential of mean force, with a reaction coordinate expressed by residue burial. Residue burials are calculated from high-resolution protein structures. The largest individual contributions to the free energy of a residue are found to be due to the hydrophobic interactions of the nonpolar atoms, interactions of the main chain polar atoms, and interactions of the charged groups of residues Arg and Lys. The contribution to the free energy of folding due to the uncharged side chain polar atoms is small. The contribution to the free energy of folding due to the main chain polar atoms is favorable for partially buried residues and less favorable or unfavorable for fully buried residues. Comparison of the accessible surface areas of proteins and model spheres shows that proteins deviate considerably from a spherical shape and that the deviations increase with the size of a protein. The implications of these results for protein folding are also discussed. PMID- 1627568 TI - Determination of kinetic constants for the interaction between a monoclonal antibody and peptides using surface plasmon resonance. AB - Differences in the affinity of a monoclonal antibody raised against the protein of tobacco mosaic virus for 15 related peptides (residues 134-146) carrying single-residue modifications were investigated using a novel biosensor technology (Pharmacia BIAcore). Analysis of the peptide-antibody interaction in real time allowed fast and reproducible measurements of both association and dissociation rate constants. Out of 15 mutant peptides analyzed, five were not recognized by the antibody at all, and seven were recognized as well as the wild-type peptide. For three of the peptides, the rate constants were different for the mutant and wild-type peptides. The pattern of residue recognition suggests that the epitope is formed by three residues (140, 143, and 144) in a helical conformation that mimics the structure in the protein. Even a minor modification of these residues totally abolishes recognition by the antibody. Modifications of adjacent residues result in small but significant differences in association and/or dissociation rate constants. One of the recognized residues is totally buried in the three dimensional structure of TMV protein, suggesting that a structural rearrangement next to the helix occurs during protein-antibody interaction. PMID- 1627569 TI - Light product of photoreactive 6-azido-FAD bound to deflavo-milk xanthine oxidase. AB - Xanthine oxidase from milk was reconstituted with the photoreactive flavin, 6 azido-FAD. While irradiation of the reconstituted enzyme under anaerobic conditions yielded 6-amino-FAD as a light product, aerobic irradiation resulted in formation of an unknown product, which gave the enzyme almost the same activity as that of the native enzyme. The light product could be extracted from the enzyme without breakdown and was found to be highly fluorescent. Upon treatment with phosphodiesterase, this light product was converted to the FMN form. The absorption spectrum of the FMN form has a peak at 464 nm, a shoulder at 450 nm in the visible region, and two peaks at 260 and 298 nm in the UV. Irradiation of free 6-azido-3-methyllumiflavin in the presence of a saturating concentration of oxygen yielded a light product whose absorbance and fluorescence spectra were very similar to those of the light product extracted from the enzyme, suggesting that the two had undergone some common photochemical change at the same place in the isoalloxazine ring. Analysis of the light product of 6 azido-3-methyllumiflavin with 1H NMR and FAB mass spectrometry suggested its possible structure with a new five-membered ring, C(6) = N-O-CH = C(7), adjacent to the benzene ring of the flavin. PMID- 1627570 TI - Mechanism of adenylate kinase. Structural and functional roles of the conserved arginine-97 and arginine-132. AB - The structural and functional roles of two conserved active site residues, Arg-97 and Arg-132, in chicken muscle adenylate kinase (AK) were evaluated by site directed mutagenesis in conjunction with one- and two-dimensional proton nuclear magnetic resonance (NMR), kinetics, and guanidine hydrochloride-induced denaturation. In addition, 31P NMR analysis was used to evaluate the contribution of Arg-97 to the phosphorus stereospecificity of AK. The results and conclusions are summarized as follows: (i) Kinetic analysis of R97M reveals 6- and 28-fold increases in the dissociation constant Ki and Michaelis constant K of AMP, respectively, and a moderate 30-fold decrease in kcat. The Ki and K values of MgATP are relatively unperturbed. The localized effect of AMP stabilization was independently confirmed by proton NMR titration, which showed a ca. 20-fold increase in the dissociation constant of AMP but not of MgATP. (ii) R132M affords a dramatic decrease in kcat by a factor of 8.0 x 10(3), with unchanged dissociation and Michaelis constants for either substrate. The lack of perturbation in the affinities toward substrates was confirmed by proton NMR titration. (iii) Although small chemical shift changes were observed for the free mutants and their complexes with substrates, further analyses by nuclear Overhauser enhanced spectroscopy with the bisubstrate analogue inhibitor, P1,P5 bis(5'-adenosyl)pentaphosphate (AP5A), indicated little perturbation in the global conformation. (iv) Contributions to conformational stability by Arg-97 and Arg-132 are negligible on the basis of the free energy of unfolding, delta GdH2O. (v) R97M was predicted and demonstrated to exhibit enhanced stereospecificity at the AMP site by at least 10-fold relative to WT in the conversion of adenosine 5' monothiophosphate to adenosine 5'-(1-thiodiphosphate). This result for R97M was predicted on the basis of the orientation of Arg-97 relative to Arg-44 and AMP in the active site as observed in available crystal structures and the stereospecificity results of R44M [Jiang, R.-T., Dahnke, T., & Tsai, M.-D. (1991) J. Am. Chem. Soc. 113, 5485-5486]. (vi) The above structural and functional analyses led us to conclude that Arg-97 interacts with the phosphoryl group of AMP, beginning at the binary complex (1-2 kcal/mol), continuing through the transition state (3.5 kcal/mol), and that Arg-132 stabilizes the transition state by greater than 5 kcal/mol. (vii) The functional importance of Arg-97 appears to be similar to that of Arg-44 [Yan, H., Dahnke, T., Zhou, B., Nakazawa, A., & Tsai, M.-D. (1990) Biochemistry 29, 10956-10964].(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1627571 TI - ATP/ADP binding sites are present in the sulfonylurea binding protein associated with brain ATP-sensitive K+ channels. AB - Covalent labeling of nucleotide binding sites of the purified sulfonylurea receptor has been carried out with alpha-32P-labeled oxidized ATP. The main part of 32P incorporation is in the 145-kDa glycoprotein that has been previously shown to be the sulfonylurea binding protein (Bernardi et al., 1988). ATP and ADP protect against this covalent labeling with K0.5 values of 100 microM and 500 microM, respectively. Non-hydrolyzable analogs of ATP also inhibit 32P incorporation. Interactions between nucleotide binding sites and sulfonylurea binding sites have then been observed. AMP-PNP, a nonhydrolyzable analog of ATP, produces a small inhibition of [3H]glibenclamide binding (20-25%) which was not influenced by Mg2+. Conversely, ADP, which also produced a small inhibition (20%) in the absence of Mg2+, produced a large inhibition (approximately 80%) in the presence of Mg2+. This inhibitory effect of the ADP-Mg2+ complex was observed with a K0.5 value of 100 +/- 40 microM. All the results taken together indicate that ATP and ADP-Mg2+ binding sites that control the activity of KATP channels are both present on the same subunit that bears the receptors for antidiabetic sulfonylureas. PMID- 1627572 TI - Apolipoprotein(a) and plasminogen interactions with fibrin: a study with recombinant apolipoprotein(a) and isolated plasminogen fragments. AB - Lipoprotein(a) [Lp(a)], but not low-density lipoprotein (LDL), was previously shown to impair the generation of fibrin-bound plasmin [Rouy et al. (1991) Arterioscler. Thromb. 11, 629-638] by a mechanism involving binding of Lp(a) to fibrin. It was therefore suggested that the binding was mediated by apolipoprotein(a) [apo(a)], a glycoprotein absent from LDL which has a high degree of homology with plasminogen, the precursor of the fibrinolytic enzyme plasmin. Here we have evaluated this hypothesis by performing comparative fibrin binding studies using a recombinant form of apo(a) containing 17 copies of the apo(a) domain resembling kringle 4 of plasminogen, native Lp(a), and Glu plasminogen (Glu1-Asn791). Attempts were also made to identify the kringle domains involved in such interactions using isolated elastase-derived plasminogen fragments. The binding experiments were performed using a well-characterized model of an intact and of a plasmin-digested fibrin surface as described by Fleury and Angles-Cano [(1991) Biochemistry 30, 7630-7638]. Binding of r-apo(a) to the fibrin surfaces was of high affinity (Kd = 26 +/- 8.4 nM for intact fibrin and 7.7 +/- 4.6 nM for plasmin-degraded fibrin) and obeyed the Langmuir equation for adsorption at interfaces. The binding to both surfaces was inhibited by the lysine analogue AMCHA and was completely abolished upon treatment of the degraded surface with carboxypeptidase B, indicating that r-apo(a) binds to both the intrachain lysines of intact fibrin and the carboxy-terminal lysines of degraded fibrin. As expected from these results, both r-apo(a) and native Lp(a) inhibited the binding of Glu-plasminogen to the fibrin surfaces.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627573 TI - The type II isoform of bovine brain protein L-isoaspartyl methyltransferase has an endoplasmic reticulum retention signal (...RDEL) at its C-terminus. AB - Bovine brain is known to contain two major isoforms of protein L-isoaspartyl methyltransferase (PIMT), an enzyme that facilitates repair of atypical L isoaspartyl peptide bonds in proteins. Although the two isoforms can be separated by anion-exchange chromatography, they appear to have similar, if not identical, substrate specificities in vitro. The more basic type I isoform has been extensively characterized, and its complete sequence has been reported. The present study was undertaken in an attempt to understand the structural and functional uniqueness of the more acidic type II isoform. Electrospray mass spectrometry of the intact enzymes revealed that the type II isoform is approximately 43 amu heavier than the type I isoform. Cyanogen bromide cleavage followed by HPLC with on-line mass analysis revealed that the type II isoform contains a unique C-terminal fragment which is 43 amu heavier than the corresponding fragment from the type I isoform. Amino acid composition analysis and direct sequencing of this fragment indicate that the type II isoform ends in the sequence ...RDEL, while the type I is known to end in ...RWK. Since ...RDEL, like ...KDEL, serves as an effective endoplasmic reticulum retention signal, we propose that the type II isoform serves to repair damaged proteins within the endoplasmic reticulum or, perhaps, within some other specialized compartment of the cell. Comparison of the protein sequences of the two bovine brain isoforms to DNA sequences for rodent PIMT reported by others suggests that the type II isoform may be produced by splicing within the codon for Arg224. PMID- 1627574 TI - Ca2+ induces transbilayer redistribution of all major phospholipids in human erythrocytes. AB - Elevating cytoplasmic Ca2+ levels in erythrocytes activates a pathway for transbilayer diffusion of plasma membrane phospholipids. The use of spin-labeled and fluorescent phospholipid analogues revealed that the pathway permits diffusion of all the major classes of phospholipids and does not distinguish between the two types of probes. Diffusion was bidirectional, began immediately upon elevation of cytoplasmic [Ca2+] above 50-100 microM, persisted as long as the [Ca2+] remained elevated, and disappeared promptly when Ca2+ levels fell. Diffusion was unaffected by conditions which suppress shedding of vesicles, discounting this event as a requisite for phospholipid reorientation induced by Ca2+. PMID- 1627575 TI - Calcium channel blockers and dysmenorrhea. AB - Dysmenorrhea is a significant problem in adolescents. Routine medical management has included analgesics and prostaglandin inhibitors. We describe the use of a calcium channel blocker, nicardipine, in the management of an adolescent who was refractory in routine treatment for severe dysmenorrhea. The patient had excellent resolution of menstrual cramping without serious side effects. The role of calcium channel blockers in the management of refractory dysmenorrhea should be further studied to examine a future role. PMID- 1627576 TI - Validity of self-report of pubertal maturation in early adolescents. AB - Self-report measures of sexual maturation continue to be used to classify pubertal development even though their reliability remains in question. This study examined the accuracy of self-report measures by early adolescents in two settings. Standardized figured drawings depicting Tanner's sexual maturation scale (SMS) were shown to early adolescents at school (S1) and again in a clinical sitting (S2), and subjects were asked to rate their own pubertal development. Physical examination by a physician at S2 was used to corroborate sexual maturation. Participating in the study were 46 males, age 11-14 years (mean, 12.4, SD, 1.9), and 37 females, age 11-14 years (mean, 12.7, SD, 0.7). Concordance rate between physical examination and self-report of pubic hair development (males) at S1 was 58% (kappa = 0.35, p less than 0.0001) and 78% (kappa = .66, p less than 0.0001) at S2. Concordance rate of self-report of genital development at S1 and S2 was 27% (kappa = -0.06, p less than 0.49) and 44% (kappa = 0.18, p less than 0.04), respectively. Self-report of breast development demonstrated a concordance rate of 59% (kappa = 0.43, p less than 0.0001) at S1 and 72% (kappa = 0.59, p less than 0.0001) at S2. Concordance rate for self-report of pubic hair development in females was 58% at S1 (kappa = 0.42, p less than 0.0001) and 75% at S2 (kappa = 0.64, p less than 0.0001). There was a tendency for subjects to overestimate their development at early stages of maturation and underestimate development at later stages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627577 TI - Reliability of adolescents' reports of height and weight. AB - The purpose of our study was to compare adolescents' self-reports of height and weight with measured height and weight to assess possible bias in self-report. The study was designed to be a cross-sectional, clinical study in a primary care Adolescent Medicine Clinic in an urban teaching hospital. The subjects were 725 consecutive patients aged 14-20 years (564 females, 161 males) with initial visits during a 2-month period. Our results showed that height was overreported by 0.5 cm and 0.6 cm by females and males, respectively. Weight was underreported by 1.5 and 1.2 kg by females and males, respectively. Differences in height or weight reports were not due to subjects' age. Females and males in the heaviest quartiles of measured weight underreported weight by significantly more than those in lighter quartiles. There were no differences in the accuracy of height or weight reports when subjects were grouped by height quartile. In conclusion, adolescents' self-reports of weight are particularly likely to differ from measured values, and these differences are largest for heavier individuals. This bias in self-report could affect results of clinical and survey research using self-report. The magnitude of such an effect would likely be small. PMID- 1627578 TI - Validity of self-reported weight and stature of American Indian youth. AB - Stature, weight, and body mass index (BMI) were obtained by self-reports and by measurements for 69 American Indian youth, 12-19 years of age, to determine the validity of self-reported values for research and clinical use. Self-reported weight was significantly less than measured weight by 2.64 kg and 2.76 kg for boys and girls, respectively. There was no systematic bias in self-reported stature in either sex. BMI based on self-reported values was significantly less than measured BMI by about 1 kg/m2 in each sex. Reporting errors for weight and BMI were related to measured size, with the greatest underestimates at the highest values of measured weight and BMI. If the patterns observed in this sample exist more widely, self-reported measures may not be acceptable proxies for measured values. PMID- 1627579 TI - Child abuse and mental health among adolescents in dependent care. AB - Do adolescents in dependent care who have been abused or neglected demonstrate more mental health problems than their nonabused peers? This study examined relationships of child abuse, depression, and self-esteem among 82 adolescents (mean age 14.5 years, 52% male, 82.9% white) living in a dependent care facility. Of these, 32 adolescents were victims of child abuse or neglect. Upon admission, 54 adolescents were identified as depressed on the Beck Depression Inventory. Initial scores on the depression and self-esteem instruments did not differ by age, race, or history of maltreatment, though trends among subtypes of abuse were identified. Females had significantly lower self-esteem and tended toward more depression. Repeat evaluation 6 months after admission revealed significant improvement in both depression and self-esteem scores for the entire sample. As a group, however, the maltreated adolescents did not demonstrate significant improvement in depression, and a history of neglect was associated with less improvement. Depression in this dependent care sample was common, however, we did not identify the maltreated adolescents as having significantly more problems with self-esteem or depression. For some adolescents, dependent care may be an appropriate and helpful alternative. PMID- 1627580 TI - Physical and sexual abuse as predictors of substance use and suicide among pregnant teenagers. AB - In order to better define risk factors for perinatal substance abuse, data from 352 pregnant teenagers enrolled in a comprehensive prenatal clinic were analyzed. Fifteen years was the average age, 82% were of minority descent, and all were receiving public assistance. At their first visit, a social worker obtained information on their home environment, family history, education, peer relationships, physical and mental health, and history of substance use. Following the interview, all teens were given a complete prenatal examination, including drug toxicology screening. The results indicate relatively low rates of substance use based on toxicology at the time of enrollment (3.6%). Self-reported rates of substance use prior to awareness of conception varied from 23% for tobacco to 17% for alcohol and marijuana; 7% of the subjects reported use of illicit substances after conception was confirmed. In addition, 80 of the 352 subjects acknowledged having been physically or sexually abused and 40 admitted to having suicidal ideation or actions. A comparison of those teenagers who had been physically or sexually abused with the remaining cohort revealed significant differences on marijuana (p less than 0.01) and cocaine (p less than 0.05) use prior to awareness of conception and on prior suicidality (p less than 0.0001). A positive history of physical or sexual abuse delineated a subset of pregnant teenagers who were at high risk for self-destructive behaviors. Teenagers in prenatal clinics should be screened, not only for current and past substance use, but also for sexual and physical abuse, domestic violence, and suicidal thoughts and actions. PMID- 1627581 TI - Attitudinal and behavioral correlates of condom use in urban adolescent males. AB - To determine correlates of condom use in adolescent males, we administered a sexual behavior questionnaire to 105 urban males attending a general adolescent clinic. The mean age was 16.5 +/- 1.6 years, and all reported heterosexual activity during the prior 3 months. Condom use was significantly (p less than 0.05) associated with perceived hassle of use (Spearman's rho = -0.40), perception of girlfriend's attitude toward condoms (rho = -0.36), self-confidence in correct use (rho = 0.26), younger age (rho = 0.25), reported degree of exposure to sexually transmitted disease (STD) education (rho = 0.23), perceived condom safety (rho = 0.23), and perceived risk of STD if not wearing a condom (rho = 0.21). Using stepwise multiple regression, four variables explained a significant amount of variation in condom use: perceived hassle of use, perceived girlfriend's attitude toward condom use, age, and self-confidence in correct use (adjusted R2 = 0.28, p less than 0.001). Intention to use free condoms was significantly (p less than 0.05) associated with past use (rho = 0.63), girlfriend's attitude toward use (rho = -0.46), self-confidence in correct use (rho = 0.36), perceived hassle (rho = -0.31), and degree of exposure to STD education (rho = 0.25). Three variables in a regression model explained a significant amount of variation in intent to use free condoms: self-reported past use, girlfriend's attitude, and self-confidence in correct use (adjusted R2 = 0.51, p less than 0.001). PMID- 1627582 TI - Comparison of human immunodeficiency virus related knowledge, attitudes, intentions, and behaviors among sexually active and abstinent young adolescents. AB - Although young sexually active adolescents are at greater risk for human immunodeficiency virus (HIV) acquisition than their abstinent peers, little is known about their respective HIV-related knowledge, attitudes, and general risk behaviors. This study of middle school adolescents (n = 1379; mean age, 13.2 years) found that the sexually active boys, compared with their peers, were less knowledgeable about HIV, less fearful of HIV, less tolerant of people with acquired immunodeficiency syndrome (AIDS), riskier in non-HIV-related attitudes and had a greater history of other risk behavior. A similar, but less marked pattern, was found for girls. It is suggested that physicians counsel all adolescents about HIV and sexuality during office visits and that early adolescent sexuality should prompt special efforts in HIV education/counseling. PMID- 1627583 TI - Barriers to adolescent prenatal care. AB - It is estimated that over one-half of all adolescent mothers receive inadequate prenatal care. Our objectives were to explore the barriers to care as perceived by adolescents and to develop a model to identify adolescents at risk for inadequate care. Structured interviews were conducted with 101 adolescents less than 17 years of age who delivered infants at an urban university hospital between September 1988 and January 1989. All the interviews were conducted within 48 hr of delivery by a single investigator. The Maternal Health Services Index was used to divide subjects into those who received inadequate care (Group 1, n = 37) and those who received intermediate or adequate care (Group 2, n = 64). Both groups were predominantly black (99%), poor (mean Hollingshead score = 2), and unmarried (99%). Groups 1 and 2 differed (p less than 0.05) in 12 variables pertaining to beliefs about prenatal care and course during the pregnancy. Of the 12 variables, 7 comprised a stepwise logistic regression model designed to maximally differentiate Groups 1 and 2--negative attitudes towards physicians (20% vs 6%), perceived importance of first trimester care (78% vs 94%), confusion about available prenatal services (24% vs 5%), lack of health insurance (41% vs 16%), exposure to pregnant friends (76% vs 95%), mean gestational age at recognition of pregnancy (15 wks vs 11 wks), and desire for an adolescent-only prenatal clinic (78% vs 58%). The adjusted odds ratios of the variables ranged in declining order from 15.4 to 4.7. The attributable risks, or etiologic fractions, of the variables ranged in increasing order from 0.19 to 0.49. Receiver-operating characteristic curve analysis of the model demonstrated a curve area of 0.89 +/- 0.04, significantly better than chance. We conclude that the model clarifies the barriers to care and helps identify pregnant adolescents who are likely to receive inadequate prenatal care. PMID- 1627584 TI - Access to health care for adolescents. A position paper of the Society for Adolescent Medicine. PMID- 1627586 TI - Glutathione S-transferase of mouse liver: sex-related differences in the expression of various isozymes. PMID- 1627585 TI - Quantitative separation of uric acid and allantoin from rat liver tissue. AB - A simple procedure is described for the assay of liver uric acid and allantoin and their specific radioactivity after administration of a radioactive precursor. Uric acid was quantified by the uricase reaction in liver trichloroacetic acid (TCA) extracts. The 'true' allantoin content of the liver could be estimated only after precipitation with Hg-acetate, a step by which the standard allantoin was also quantitatively recovered. Crude extracts lead to the evaluation of 'apparent' allantoin. For the determination of specific radioactivity, the Hg acetate precipitate was further purified by ion-exchange chromatography. The purity of the two metabolites was confirmed by ultraviolet absorbance spectra, HPLC, constancy of specific radioactivity and the absence of amino acids. The incorporation of [14C]formate into uric acid and allantoin in the liver was studied by this procedure. The radioactivity in allantoin was several-fold higher than that in uric acid up to 60 min after administration of the precursor. This quite unexpected result is not easily explained on the basis of current knowledge. PMID- 1627587 TI - Time course characterization of the induction of cytochrome P-450 2E1 by pyrazole and 4-methylpyrazole. AB - Cytochrome P-450 (P-450) 2E1 is under transcriptional and post-transcriptional control. Well-defined time courses were carried out to compare the effect of pyrazole and 4-methylpyrazole on catalytic activities, apo-P-450 2E1 levels and mRNA levels to evaluate whether induction of P-450 2E1 is preceded by altered mRNA levels. Two days of treatment with pyrazole or three days of treatment with 4-methylpyrazole resulted in significant induction of P-450 2E1, as assessed by Western blots and by oxidation of dimethylnitrosamine or p-nitrophenol. No changes in mRNA levels were detected with either inducer. Within 2 h of the second treatment with pyrazole, maximal induction of P-450 2E1 was observed, however, a 8-12 h time-dependent period was required after the third treatment with 4-methylpyrazole for maximal induction. Irrespective of the time period, increased catalytic activity and P-450 2E1 appears to reflect a post transcriptional mechanism. A single treatment with 4-methylpyrazole increased P 450 2B1/B2 levels and oxidation of pentoxyresorufin about 2- to 3-fold. No change in mRNA levels for 2B1/B2 was observed. Although significant, the induction of 2B1/B2 by 4-methylpyrazole is more than an order of magnitude less than that by phenobarbital. Pyrazole did not induce 2B1/B2. It appears that, similar to acetone and ethanol, 4-methylpyrazole may increase several P-450 isozymes, whereas pyrazole is more specific for induction of P-450 2E1. PMID- 1627588 TI - Purification and partial characterization of xanthine oxidase from human milk. AB - Xanthine oxidase was purified from human milk in yields comparable with those obtained from bovine milk. The freshly purified enzyme appeared homogeneous in gel permeation FPLC and SDS-PAGE, consistent with its being a homodimer with total M(r) 290,000 +/- 6000. The ultraviolet/visible absorption spectrum differed only slightly from that of bovine milk enzyme and showed an A280/A450 ratio of 5.13 +/- 0.29, indicating a high degree of purity. Xanthine oxidase activities of purified enzyme varied with batches of milk, ranging between 3 and 46 mU/mg protein; values that are some two to three orders of magnitude smaller than those shown by the most highly purified samples of bovine milk enzyme. Direct comparison with commercially-available bovine milk enzyme showed that activities involving xanthine as reducing substrate were 1-6% that of the bovine enzyme, whereas those involving NADH, in contrast, were of the same order for the two enzymes. Anaerobic bleaching experiments indicated that less than 2% of the human enzyme was present as a form active with xanthine. These findings, together with the activity data, are consistent with a very high content, possibly greater than 98%, of demolybdo- and/or desulpho-forms of human enzyme, both of which occur, to a lesser extent, in bovine xanthine oxidase. Molybdenum assay indicated that demolybdo-enzyme could only account for some 26% of this inactive component, suggesting that desulpho-enzyme may account for the remainder. PMID- 1627589 TI - Interaction of carnitine with mitochondrial cardiolipin. AB - The physiological role of L-carnitine is to determine the transport of acyl-CoA through the mitochondrial membrane. However, some observations may also suggest a direct effect of the molecule per se on the physical properties of the membrane, most probably at the level of the binding site. This possibility has been investigated by studying the influence of adriamycin, a drug that binds to cardiolipin, on the effect of carnitine on isolated rat liver mitochondria. It has been found that adriamycin almost abolishes the activating effect of carnitine on state 2 respiration. The effect and its inhibition is seen by using either the L-form of carnitine or the D-form or both. Cardiolipin removes the effect of adriamycin and restores the activation by carnitine. It is proposed that some effects of carnitine on mitochondrial properties may be the result of interaction of carnitine with cardiolipin at the membrane level. PMID- 1627590 TI - Insulin binding to liver nuclei from lean and obese mice is altered by dietary fat. AB - Insulin binding to the plasma membrane is known to be altered by modifying the membrane composition through dietary treatment. As insulin binding receptors are also present on nuclear membrane, this study was undertaken to investigate if specific binding of insulin to the liver nuclei is altered by diet. 8-wk-old female C57 B 6J lean and ob/ob mice were fed semipurified diets containing 20% (w/w) fat of either high or low polyunsaturated-to-saturated (P/S) fatty acid ratio for 4 wk. Liver nuclei were prepared, insulin binding was measured and nuclear phospholipids were isolated for lipid analysis. Insulin binding was highest in nuclei prepared from lean mice fed a high P/S diet. Specific binding of insulin to nuclei prepared from obese mice was also increased by the high P/S diet, but to a lesser extent compared to lean mice. Feeding a high P/S diet increased polyunsaturated fatty acid content of membrane phospholipids from both lean and ob/ob mice. Obese mice were characterized by higher levels of arachidonic acid and lower levels of linoleic acid in phosphatidylcholine. The present study establishes that insulin binding to liver nuclei is increased by feeding a high P/S diet, and that insulin binding to liver nuclei from obese mice is lower than from lean mice. PMID- 1627591 TI - The structural elucidation of the two positional isomers of a mono-glucopyranosyl mono-acyl glycerol derivative from Cystobacter fuscus (Myxobacterales). AB - The structures of two glycolipids produced by Cystobacter fuscus Cb 685 have been determined by 1H-NMR spectroscopy including 2D-techniques, as the positional isomers 1- and 2-isopentadecanoyl-3-beta-D-glucopyranosyl-X-glycerol. The chain length of the fatty acid residue determined by 13C-NMR spectroscopy has been confirmed by negative ion FAB-mass spectrometry. PMID- 1627592 TI - An anti-probasin monoclonal antibody recognizes a novel 40-kDa protein localized in rat liver and a specific region of kidney urinary tubule. AB - Immunoblotting with a monoclonal antibody against probasin (rat prostatic secretory protein) showed that a 40-kDa protein antigenically related to probasin was localized in rat liver and kidney. The contents of probasin in these organs were negligible. Immunostaining revealed that the 40-kDa protein (probasin related antigen: PRB-RA) was expressed in the liver parenchymal cells and the kidney urinary tubular epithelial cells in outer stripe. The content of PRB-RA in the kidney was low during 0 to 2 weeks of age, then rapidly increased about 10 fold from 2 to 8 weeks of age. The content in the liver increased about 2-fold during the period, reaching a value of 10-12 ng/micrograms protein, which was ten times higher than that in the kidney. PRB-RA was purified from rat liver by ion exchange chromatography, gel filtration and fast protein liquid chromatography on a hydroxyapatite column. The purified protein formed insoluble aggregates in the absence of a detergent, and it had a blocked amino terminal. The amino acid sequence of a peptide generated by tryptic digestion of alkylated PRB-RA was determined. Computer analysis showed that there was no protein having a significant homology with the peptide. These results indicate that a novel 40-kDa protein with a structural similarity to probasin is localized in rat liver and kidney, and might bear a function specific to these organs. PMID- 1627593 TI - Identification of a rhodopsin photoreceptor in Euglena gracilis. AB - Visual pigments are a class of receptor proteins that absorb light and trigger sensory signals. Retinal-containing proteins are used in nature as photoreceptors mainly in animals vision. Mammalian rhodopsin is the best studied example of a light sensor which couples photon absorption to a cascade of biochemical reactions amplifying the input signal. A surprising discovery was to find rhodopsin also in Archaebacteria and in unicellular eukaryotes. On the basis of absorption microspectroscopic measurements and of inhibition experiments on pigment biosynthetic pathways, we have recently suggested that a rhodopsin could be the functional receptor of the visual process in Euglena gracilis, a flagellate which can use light directly to promote photosynthetic reactions, or as an incident flux of information to adjust its swimming orientation. We here report purification and identification of all-trans-retinal by column chromatography, HPLC and GC-MS in E. gracilis; these findings indicate with absolute certainty that rhodopsin is the photoreceptor molecule of this microorganism. PMID- 1627594 TI - Isolation and characterization of type IX collagen-proteoglycan from the Swarm rat chondrosarcoma. AB - Type IX collagen was partially purified from the Swarm rat chondrosarcoma by a series of a conventional salting-out procedures. The preparation was further separated by anion exchange chromatography into an unbound and a bound fraction in an A230 ratio of about 5:1. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the bound fraction appeared as a broad band, whose molecular mass ranged from 250 to 270 kDa. Digestion with chondroitinase ABC reduced the apparent molecular mass of the bound fraction to about 250 kDa, a value comparable to the molecular mass of the unbound fraction. Tryptic peptide maps of the protein moieties of unbound and bound forms showed that their molecular structures were basically identical. A monoclonal antibody specific for LMW, one of the pepsin-resistant fragments of the rat sarcoma type IX, reacted with both the unbound and bound fractions. Together the results indicate that the unbound and bound fractions represent a type IX collagen devoid of the chondroitin sulfate chain and its proteoglycan form with covalently bound chondroitin sulfate, respectively. The extent of glycosaminoglycan attachment to type IX collagen molecules in rat chondrosarcoma (about 16%) is quite different from the extents described in chick embryo cartilage (about 80%), chick vitreous humour (100%) and bovine cartilage (less than 5%). Further studies on the neoplastic tissue will offer additional information regarding the biological basis and biological consequences of the glycosaminoglycan attachment to type IX collagen molecules. PMID- 1627595 TI - Formation, separation and characterization of three beta-1,3-glucanases from Sclerotium glucanicum. AB - The appearance of beta-1,3-glucanases in supernatants of Sclerotium glucanicum cultures was followed by SDS-PAGE and shown to be dependent on cultivation time. Three beta-1,3-glucanases were isolated and purified. Glucanase I and III appeared homogeneous on SDS-PAGE with molecular masses of 85 and 33.5 kDa, respectively. Enzyme I was an endo-splitting beta-1,3-glucanase. In hydrolyzing laminarin it released glucose, laminaritriose and laminaribiose as major endproducts and smaller amounts of higher oligosaccharides. Enzyme III was an exo beta-1,3-glucanase removing glucose from laminarin and gentiobiose and glucose from scleroglucan. For laminarin as substrate the Km of enzyme I and III was 2.5 and 3.33 mg/ml, respectively. Enzyme II was only partially purified and found to be also an exo-beta-1,3-glucanase, releasing glucose as the only hydrolysis product from laminarin. It did not attack scleroglucan. Its molecular weight was determined to be 78 kDa. Optimum pH and temperature of the three enzymes were determined. The three activities were significantly inhibited by 1 mM Hg2+. PMID- 1627596 TI - Evaluation of the amount of acyl-CoA elongases in leek (Allium porrum L) leaves. AB - Polyclonal antibodies have been raised against the acyl-CoA elongase purified from leek epidermal cells. The antibodies recognize the fractions containing the elongating activity after DEAE or Ultrogel chromatography and their response with the other fractions is very low. The immune complex is immunoprecipitable with Protein A-Sepharose. 1% of the solubilized proteins from leek epidermis microsomes are immunoprecipitated. The immunoprecipitate contains an elongating activity which is 86 +/- 20-times that of the unbound fraction. PMID- 1627597 TI - Further mechanistic study on intestinal absorption enhanced by unsaturated fatty acids: reversible effect by sulfhydryl modification. AB - In order to study the relationship between the sulfhydryl (SH) modification of membrane-associated proteins and the oleic acid-induced permeability enhancement of the colonic mucosa, in vitro and in situ absorption studies were performed using rat colon and carboxyfluorescein as an impermeable dye. The pretreatment of the mucosa with diamide, a bifunctional sulfhydryl modifier, in in vitro experiments with the everted colonic loops reduced the absorption enhancing effect of oleic acid in a concentration-dependent manner, less inhibitory effect, though just a little, was observed as compared to N-ethylmaleimide. The inhibition caused by the addition of diamide was absolutely restored by exposure of the mucosa to dithiothreitol. On the other hand, these SH modifiers showed no pronounced effect on the in vivo permeability of quinine which is well-known to be absorbed by a passive transport system mainly via the membrane lipid bilayer. These results obtained in the present study have identified an important role of the functional SH groups of membrane proteins on modulating the permeability alteration of the mucosal epithelium provoked by oleic acid. Furthermore, the SH proteins have been revealed as being unimportant in the intestinal absorption of lipoid-soluble compounds. PMID- 1627598 TI - Identification and purification of a novel serine/threonine messenger-independent growth-related protein kinase from lactating goat mammary gland. AB - A second messenger-independent serine/threonine protein kinase from lactating goat mammary gland is purified and characterized. The purification steps include: homogenization, ultracentrifugation, ammonium sulphate precipitation, DEAE Sepharose, phosphocellulose, hydrophobic and Mono Q columns. On the final step of purification the enzyme is revealed as a single band of mol wt 45,000 on silver stained SDS-PAGE. Mg2+ and K+ are necessary for its optimum activity. Phosvitin and casein are substrates for the enzyme but kemptide, RRREEETEEE, protamine and histone mixture are all poorly phosphorylated. The kinase is inhibited by quercetin, heparin, random tyrosine- and glutamic acid-containing polymers, Ca2+, NaF, 2,3-bis-phosphoglycerate. 1 mM Mn2+ affects positively the basal level of the kinase activity but 5 mM Mn2+ completely suppress the effect of 10 mM Mg2+. Km of this enzyme for ATP is 1.57 microM and pH optimum is from 6 to 7. Isolation of this kinase is facilitated by its unusually high affinity for phosphocellulose. PMID- 1627599 TI - Generation of one set of monoclonal antibodies specific for a-pathway ganglio series gangliosides. AB - We established five murine monoclonal antibodies (MAbs) specific for a-pathway ganglio-series gangliosides by immunizing C3H/HeN mice with these purified gangliosides adsorbed to Salmonella minnesota, followed by fusion with mouse myeloma cells. The binding specificities of these MAbs were determined by enzyme linked immunosorbent assay and immunostaining on thin-layer chromatogram. These five MAbs, designated GMR6, GMB28, GMB16, GMR17, and GMR11 reacted strongly with the gangliosides GM3, GM2, GM1, GD1a, and GT1a, respectively, that were used as immunogens. Three MAbs, GMB28 (anti-GM2), GMB16 (anti-GM1), and GMR11 (anti-GT1a) showed highly restricted binding specificities, reacting only with the immunizing ganglioside. None of the other various authentic gangliosides or neutral glycolipids was recognized. On the other hand, the other two MAbs, GMR6 (anti GM3) and GMR17 (anti-GD1a) exhibited broader specificities. MAb GMR6 cross reacted with GM4, GM1b, GD1a, GT1b, and IV3NeuAc alpha-nLc4Cer. MAb GMR17 also reacted with GM1b and GT1b. Neither GMR6 nor GMR17 reacted with other gangliosides or neutral glycolipids tested. Using these MAbs, we determined the expression of these gangliosides, especially GM1, GD1a, and GT1a on mouse, rat and human leukemia cells. GM1 and GD1a were expressed on some leukemia cells, whereas GT1a was not detected in these cells. PMID- 1627600 TI - Molecular expression of the negative growth factor murine beta-galactoside binding protein (mGBP). AB - Characterisation of the negative growth factor mGBP at molecular and biological levels indicates that the protein has no lectin nature and suggests instead a participation in the cytokine network. The protein is shown to be expressed as a monomer in two forms, one of which is non-covalently linked to a glycan complex. This confers greater efficiency to the inhibitor and may favour a paracrine role. The two monomeric forms may oxidise into tetramers which retain biological activity, but lack ability to link to specific saccharide residues. PMID- 1627601 TI - Molecular aging of lens crystallins and the life expectancy of the animal. Age related protein structural changes studied in situ by Raman spectroscopy. AB - In order to investigate the relationship of molecular aging of lens crystallins to an animal's life expectancy or to the type of the lens, Raman spectra have been measured in situ for rabbit and guinea-pig lens nuclei at various stages of aging; these spectra have been compared with those of rat and mouse lens nuclei previously reported. Lens aging results in pronounced differences among the Raman spectra of the lens nuclei of the four species. It is shown that the rates of dehydration, inter- and intramolecular disulfide bond formation, and microenvironmental changes in the tryptophan residues of lens crystallins are different among the four species. Much faster changes occur for rat and mouse, which have a shorter life expectancy (2 years) and give rise to hard lens nuclei while slower changes occur for rabbit and guinea-pig, which have a longer life expectancy (5-7 years), and give soft lens nuclei. In addition, the Raman data reveal, for all the species investigated, that there are correlations among the rates of the dehydration, the inter- and intramolecular disulfide bond formation, and the microenvironmental changes in the tryptophan residues. Therefore, there seems to be a common mechanism for molecular aging of lens crystallins among the four species, although the rate of the molecular aging strongly depends upon the life expectancy of the animal and the type of the lens. The most important factor determining the rate of the molecular aging is probably the dehydration which decreases free water in the lens nucleus. PMID- 1627602 TI - Mapping of the active site of T7 RNA polymerase with 8-azidoATP. AB - The photoaffinity analog of ATP, 8-azidoATP, labels T7 RNA polymerase. Photoincorporation exhibits saturation behavior and is protected against by the substrate ATP. 8-AzidoATP is a competitive inhibitor of ATP incorporation with Ki approximately 40 microM. The photolabeled T7 RNA polymerase, following cyanogen bromide digestion, was analyzed by phenylboronate agarose column chromatography followed by reverse-phase high pressure liquid chromatography. Sequencing of the peptides labeled with radioactive photoprobe allowed the identification of three peptides, P314-M362 (I), L550-M666 (II), and F751-M861 (III). These peptides are in the proximity of the photoprobe 8-azidoATP and, therefore, expected to contain functionally significant residues and define an active site domain. These peptides (I and II) contain residues previously implicated in T7 RNA polymerase activity or show homology to active site regions of the Klenow fragment of DNA polymerase I (II and III). PMID- 1627604 TI - Temperature-jump studies and polarized absorption spectroscopy of methemoglobin thiocyanate single crystals. AB - Association equilibria and association kinetics of the thiocyanate binding reaction to methemoglobin in single crystals and solution are studied using temperature-jump technique and polarized absorption spectroscopy. Different kinetic constants are found for the reaction in solution and crystal phase for the alpha- and beta-subunits of the methemoglobin tetramer. The reduction of the reactivity of the alpha- and beta-subunits in crystalline phase is 6-fold and 2.4 fold, respectively, compared to the values found in solution. The intramolecular binding reaction of the N epsilon of the distal histidine E7 which is observed in methemoglobin in solution cannot be detected in single crystals. Our results suggest that crystallization of hemoglobin has little influence on small-scale structural fluctuations which are necessary for ligands to get to the binding sites and large-scale structural motions are suppressed. PMID- 1627603 TI - Human red cell acid phosphatase (ACP1): the primary structure of the two pairs of isozymes encoded by the ACP1*A and ACP1*C alleles. AB - The Af, As, Cf and Cs isozymes encoded by the human red cell acid phosphatase ACP1*A and ACP1*C alleles, respectively, have been sequenced. All four isozymes consist of a single non-glycosylated peptide chain (157 residues), acetylated at the amino-terminal alanine residue. Each f isozyme differs from the corresponding s isozyme over the sequence segment 40-73, while the remaining four-fifth of the molecules are identical. These findings are consistent with results for the Bf and Bs isozymes encoded by the common ACP1*B allele and confirm that the presence of a specific f or s segment is a common property to ACP1 isozymes. This supports our hypothesis that f and s isozymes are generated by alternative splicing of exons in the primary RNA transcript. Cf and Cs are identical in sequence with Bf and Bs, respectively. Thus, the ACP1*B and ACP1*C alleles encode exactly the same pair of isozymes, the only difference at the protein level being the ratio of f and s isozyme. Af and As differ from the Bf and Bs isozymes by a single substitution at residue 105; Arg and Gln, respectively. These observations explain the electrophoretic identity of the B and C isozyme pairs and the higher P(i) of the A isozyme pair. PMID- 1627605 TI - Secondary structure of synthetic peptides derived from the repeating unit of a giant secretory protein from Chironomus tentans. AB - The secretory proteins of Chironomus tentans larvae, which are used to construct underwater feeding and pupation tubes, assemble into complexes in vitro. Members of a family of 1000 kDa proteins, the spIs, appear to form the fibrous backbone of the assembled complexes. The spIs consist of a core of tandemly repeating units of 60 to 90 amino acids that can be subdivided into two regions: the subrepeat region, made up of short internal repeats, and the constant region, which lacks simple subrepeats. We have synthesized peptides representative of the constant and subrepeat regions of one of the spIs, and have examined their secondary structure using Fourier transform IR and CD spectroscopy. The IR spectrum of the constant peptide indicates that this peptide has alpha-helical regions and beta-turns. The CD spectrum confirms this. The IR spectrum of the subrepeat peptide is similar to that of the poly(Gly)II helix, and also may indicate the presence of beta-turns. The CD spectrum is consistent with this helical structure. Extrapolation of these results to intact spIs is in agreement with secondary structure prediction and modeling studies. Our results indicate that the alpha-helices and poly(Gly)II-like helices are not arranged as coiled coils, which are often found in fibrous proteins. We suggest that these structural elements may be in an unusual arrangement in the spIs, organized as alternating alpha-helices and poly(Gly)II or collagen-like helices, interspersed with beta-turns. PMID- 1627606 TI - Recombinant bovine rhodanese: purification and comparison with bovine liver rhodanese. AB - Recombinant bovine rhodanese (thiosulfate: cyanide sulfurtransferase, EC 2.8.1.1) has been purified to homogeneity from Escherichia coli BL21(DE3) by cation exchange chromatography. Recombinant and bovine liver rhodanese coelectrophorese under denaturing conditions, with an apparent subunit molecular weight of 33,000. The amino terminal seven residues of the recombinant protein are identical to those of the bovine enzyme, indicating that E. coli also removes the N-terminal methionine. The Km for thiosulfate is the same for the two proteins. The specific activity of the recombinant enzyme is 12% higher (816 IU/mg) than that of the bovine enzyme (730 IU/mg). The two proteins are indistinguishable as to their ultraviolet absorbance and their intrinsic fluorescence. The ability of the two proteins to refold from 8 M urea to enzymatically active species was similar both for unassisted refolding, and when folding was assisted either by the detergent, lauryl maltoside or by the E. coli chaperonin system composed of cpn60 and cpn10. Bovine rhodanese is known to have multiple electrophoretic forms under native conditions. In contrast, the recombinant protein has only one form, which comigrates with the least negatively charged of the bovine liver isoforms. This is consistent with the retention of the carboxy terminal residues in the recombinant protein that are frequently removed from the bovine liver protein. PMID- 1627608 TI - Glycosylation of membrane cofactor protein (CD46) in human trophoblast, kidney and platelets. AB - Many cell surface glycoconjugates are differentiation markers and are involved in cell-cell and intermolecular interactions in development, immunity and cancer. Membrane cofactor protein (MCP) comprises structurally related 65 and 55 kDa glycoproteins that bear O- and N-linked glycans. MCP prevents amplification of autologous complement action on human cells. We used immunoblotting with MCP specific monoclonal antibody TRA-2-10 to determine lectin-binding properties and glycosidase sensitivities of MCP in a study of cell-specific variation in glycosylation of this protein. The results showed that N-linked glycans on placental syncytiotrophoblast and cytotrophoblast, kidney and platelet MCP are similar in binding to concanavalin A and Lens culinaris lectins, but are not bound by leucophytohemagglutinin. Lectin binding prior to and after neuraminidase digestion indicates that MCP from these sources is highly sialylated. 65 kDa MCP was confirmed to contain more O-linked glycans than 55 kDa MCP. A fraction of platelet 65 kDa MCP is distinct, however, in bearing peripheral fucose residues. Syncytiotrophoblast is unique in containing a 110 kDa form of MCP in non-reducing SDS-PAGE that resembles 65 kDa MCP in glycosylation. Chorion laeve MCP in 4 of 8 preparations was unusually heterogeneous and differed from syncytiotrophoblast MCP after neuraminidase digestion in the forms bound to peanut agglutinin and WGA. The results indicated for the first time, differences in O-linked glycosylation of MCP in chorion laeve cytotrophoblast relative to syncytiotrophoblast, platelet and kidney MCP. We conclude that structures of MCP glycans can differ between trophoblasts and other cell types. PMID- 1627607 TI - Inhibition of Clostridium perfringens phospholipase C by ammonium and sulfonium dications. AB - Polyamines, alkyldiammonium and alkyldisulfonium salts, inhibit the Clostridium perfringens phospholipase C-catalyzed hydrolysis of 1-S-phosphocholine-2-O hexadecanoyl-1-mercapto-2-ethanol (1) at pH 7.5, 37 degrees C, mu = 1.0 with KCl. Simple saturation kinetics are observed as both 1 and [Ca2+] are varied and simple linear inhibition is observed. The data are consistent with a non competitive mechanism that involves binding of the inhibitors to free enzyme, E.[Ca2+] and E.[Ca2+].[S]; the inhibition constants for decamethylenebis(trimethylammonium) and decamethylenebis(dimethylsulfonium) bromides are 90 and 0.28 mM, respectively. It is suggested that the enhanced inhibition by the alkyldisulfonium salts results from more favorable equilibrium constants for contact ion-pair formation or from the formation of tetracoordinate sulfuranes. PMID- 1627609 TI - Rearrangements of the nucleosome structure in chromatin by poly(ADP-ribose). AB - In order to approach and clarify the effect of poly(ADP-ribose) on the nucleosomal structure, polynucleosomes from calf thymus were incubated with long poly(ADP-ribose) chains prepared in vitro and examined by ELISA with antibodies directed against the five individual histones H1, H2A, H2B, H3 and H4 as well as against two synthetic peptides in residues 1-25 of H2B and 130-135 of H3. The results showed that: (i) free ADP-ribose polymers did indeed interact with the nucleosomes; (ii) the accessibility of epitopes recognized by any of the different antibodies was altered, the binding of antibodies being increased or decreased depending on the quantity of poly(ADP-ribose) added thereby suggesting a modulation in nucleosome structure; (iii) for any ADP-ribose polymer concentration, core histones as well as histone H1 were always recognized by their respective antibodies, thus suggesting that poly(ADP-ribose) does not seem to cause complete stripping of histones from nucleosomal DNA. PMID- 1627610 TI - Methionine oxidation and inactivation of alpha 1-proteinase inhibitor by Cu2+ and glucose. AB - The effect of glucose/Cu2+ incubation on (a) pure methionine oxidation, (b) the oxidation of active-site methionine in alpha 1-proteinase inhibitor (alpha 1PI) and (c) the resulting activity and structural changes of this inhibitor was investigated. While no methionine was oxidized during a 24 day, 37 degrees C incubation with 0.01 M EDTA and 100 mM glucose, 64.2% oxidation occurred in 6 days when 0.01 mM Cu2+ was added to the 100 mM glucose. The first-order rate constant for oxidation in 10 mM glucose, 0.01 mM Cu2+ was 0.0218 day-1. Oxidation was inhibited by catalase, but accelerated by ascorbate ion. The active-site methionyl residue of alpha 1PI was oxidized 71.3% after a 4 day incubation in 100 mM glucose, 0.01 mM Cu2+ (pH 7.45), 0.1 M phosphate buffer. The elastase and trypsin inhibiting activities were lowered to 3.1 and 1.5% of control samples during this incubation. The inclusion of 1 mM DETAPAC, a transition metal chelator, resulted in a 98 + % retention of activity. Intrinsic fluorescence (350 nm excitation, 415 nm emission) of alpha 1PI increased 576% over control for the sample incubated in 100 mM glucose, 0.01 mM Cu2+ and SDS-PAGE revealed protein fragment molecular weights of 44.4 and 39.8 kDa. These studies suggest that both methionine oxidation and free radical induced fragmentation contribute to loss of alpha 1PI activity during glucose/Cu2+ incubations. PMID- 1627611 TI - Specific identification of human ribonucleases by antibodies produced against two synthetic peptides corresponding to the N- and C-terminal amino-acid sequences of human urinary secretory-type ribonuclease. AB - Antibodies were raised in rabbits by immunizing two synthetic peptides, which corresponded to the N- and C-terminal 15 residues, respectively, of human urinary secretory ribonuclease (RNase). These antibodies did not block the RNase activity, but reacted well with enzymes blotted onto a transfer membrane following electrophoresis, and discriminated strictly between secretory- and nonsecretory-type RNases. Therefore, these antibodies should to be valuable tools for the immunological identification of human RNases. PMID- 1627612 TI - Expression and purification of human angiotensinogen in Chinese hamster ovary cells. AB - We have produced human angiotensinogen in Chinese hamster ovary (CHO) cells. The expression products were purified to homogeneity by a single column chromatography and its 17 amino-terminal sequences were identical to those of the native protein. We demonstrated the recombinant human angiotensinogen to be a substrate for human renin. PMID- 1627613 TI - Unsaturated and branched chain-fatty acids in temperature adaptation of Bacillus subtilis and Bacillus megaterium. AB - The effect of growth temperature on the cellular fatty acid profiles of Bacillus subtilis and Bacillus megaterium was studied over a temperature range from 40 to 10 degrees C. As the growth temperature of B. subtilis was reduced, the lower melting point anteiso-acids increased, while the higher-melting point iso-acids decreased. Consequently the ratio of branched- to straight-chain acids was unaffected by temperature, although changes in the position of fatty acid branching and the degree of unsaturated branched-chain fatty acids occurred. In B. megaterium a more complicated, biphasic behaviour was observed. Saturated, straight-chain and iso-branched acids decreased only from 40 degrees C down to 20 26 degrees C, and anteiso-acids decreased only from 20-26 degrees C to 10 degrees C, while unsaturated acids increased over the whole temperature range studied. Thus, in B. megaterium total branched-chain acids decreased and straight-chain acids increased as temperature decreased. However, the overall cellular content of lower-melting point fatty acids increased with decreasing temperature in both bacilli, and unsaturated fatty acids appeared to be essential components in the adaptation of the microbes to changes in temperatures. Since changes in the relative amounts of branched- and straight-chain fatty acid biosynthesis are known to reflect differences in fatty acid primers, temperature seems to affect not only the activity of the fatty acid desaturases but also the formation or availability of these primers. The results indicate, however, that notable species-specific regulatory features exist in this genus of bacteria. PMID- 1627614 TI - Polyunsaturated fatty acid incorporation into plasmalogens in plasma membrane of glioma cells is preceded temporally by acylation in microsomes. AB - Plasmalogens (1-O-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine) are major phospholipids in many tissues and cells, particularly of neural origin. Using cultured C6 glioma cells and subcellular fractions isolated on Percoll gradients we investigated selectivity for esterification of several polyunsaturated fatty acids (PUFA) in the sn-2 position of plasmalogens compared to [1-14C]hexadecanol, representative of de novo synthesis of the ether-linked sn-1 position. In whole cells at a final concentration of 105 microM PUFA, 2-4 nmol plasmalogen/mg protein was labeled in 4 h and 10-14 nmol in 24 h, representing 8-15% and 35-50%, respectively, of initial plasmalogen mass. Incorporation of label from hexadecanol was lower than PUFA incorporation (20:5(n-3) greater than 20:4(n-6) greater than 18:3(n-3) much greater than 18:2(n-6)) suggesting deacylation reacylation at the sn-2 position. Plasmalogens accounted for 50% of total cell ethanolamine phospholipids and 75% in plasma membrane. Using a novel, improved method for extraction of subcellular fractions containing Percoll, plasma membrane also was enriched in plasmalogen relative to microsomes (107.4 +/- 5.2 vs. 40.0 +/- 2.9 nmol/mg protein). Selectivity for esterification at the sn-2 position of plasmalogens with respect to chain length and unsaturation of the fatty acyl chain was similar in both subcellular fractions and reflected that of whole cells. Labeling of plasma membrane with PUFA and fatty alcohol lagged behind that of microsomes. Chase experiments in cells prelabeled with [1 14C]18:3(n-3) for 2 h showed no significant reduction of label in plasmalogen of any subcellular fraction although accumulation of label in the microsomal fraction was slowed initially. Reduction of plasmalogen label (40-50%) did occur in microsomes and plasma membrane when cells prelabeled for 24 h were switched to chase medium with or without chase fatty acid. Our data suggest that esterification of PUFA to plasmalogen may occur at the endoplasmic reticulum with subsequent translocation to plasma membrane resulting in accumulation of relatively stable pools of plasmalogen that are not readily accessible for deacylation-reacylation exchange with newly appearing PUFA. Alternatively, deacylation-reacylation may occur in a more stable phospholipid pool within the plasma membrane but would involve a slower process than at the endoplasmic reticulum. PMID- 1627615 TI - Solubility of long-chain fatty acids in phosphate buffer at pH 7.4. AB - The solubility of the saturated fatty acids lauric, myristic, palmitic, and stearic acid and the unsaturated oleic acid at 37 degrees C in phosphate buffer (pH 7.4) was estimated by using two independent methods. The one was a conventional solubility technique measuring the concentration of dissolved fatty acid in buffer by using radioactive compounds. The other was a dialysis exchange technique monitoring possible aggregation of solvated fatty acid anions by measuring the rate of diffusion of labelled compound across a dialysis membrane under conditions of chemical equilibrium. It was found that the results were strongly dependent on the radiochemical purity of the fatty acids. Using highly purified samples of radioactively labelled fatty acids, the solubility of monomeric laurate was shown to be greater than 500 microM, whereas the solubility of monomeric myristate was found to be 20-30 microM. Palmitate, stearate, and oleate solutions, on the other hand, showed a tendency to aggregation even at concentrations below 1 microM. Special attention was given to palmitate, as a reference compound for long-chain fatty acids, and the solubility of monomeric palmitate was estimated to be lower than 10(-10) M. PMID- 1627616 TI - Effect of the human cholesteryl ester transfer protein on the particle size redistribution of specific subpopulations of high density lipoproteins-3. AB - The effect of the cholesteryl ester transfer protein (CETP) on the size redistribution of high density lipoprotein-3 (HDL3) particles containing either apolipoprotein A-I without apolipoprotein A-II, designated HDL3 (A-I w/o A-II), or apolipoprotein A-I with apolipoprotein A-II, designated HDL3 (A-I w A-II), was investigated by incubating HDL3 at 37 degrees C in the presence of a purified preparation of CETP. At the end of the incubation, the distribution of total HDL3 as well as HDL3 (A-I w/o A-II) particles, recovered after immunoprecipitation of HDL3 (A-I w A-II) particles with anti-apo A-II antibodies, was determined by non denaturing polyacrylamide gradient gel electrophoresis. Total HDL3 ultracentrifugally isolated from plasma consisted of two distinct subpopulations of particles with apparent diameters of 8.5 and 7.8 nm. The distribution profile of HDL3 (A-I w/o A-II) particles, revealed that the HDL3 subpopulation with a mean diameter of 8.5 nm comprised two typs of particles, containing either only apo A-I or apo A-I with apo A-II, while the lipoprotein subpopulation with a mean diameter of 7.8 nm consisted exclusively of particles containing both apolipoproteins. During incubation at 37 degrees C, CETP induced the redistribution of HDL3 with a mean apparent diameter of 8.5 nm towards particle subpopulations of larger (9.4 nm diameter) and smaller (7.8 and 7.4 nm diameter) size. It was demonstrated that the CETP-mediated conversion of HDL3 concerned both type of particles. CETP preferentially induced the transformation of HDL3 (A I w A-II) particles with a mean diameter of 8.5 nm into larger (9.4 nm diameter) and smaller (7.8 nm diameter) particles containing apo A-I and apo A-II. Secondly, CETP induced a shift of HDL3 (A-I w/o A-II) particles with a mean diameter of 8.5 nm towards particles of smaller size (7.4 nm diameter) containing only apo A-I, while HDL3 (A-I w A-II) particles with mean diameters of 7.8 and 9.4 nm remained stable. In addition, this study demonstrated that the redistribution of HDL3 particles was accompanied by a dissociation of apolipoprotein A-I from the lipoprotein surfaces. The effect of myristic acid on CETP-induced HDL3 redistribution was mainly due to a redistribution of HDL3 (AI w/o AII) particles. PMID- 1627617 TI - Characterization of a bile salt-dependent cholesteryl ester hydrolase activity secreted from HepG2 cells. AB - HepG2 cells and medium were assayed for cholesteryl ester hydrolase (CEH) activity in the presence and absence of sodium cholate. Although bile salt dependent CEH activity was measured in the medium at 6 to 96 h (up to 4500 pmol/h per mg cell protein), there was very little activity detected in the corresponding cell homogenates (less than 70 pmol/h per mg cell protein). Activity in the medium was expressed only in the presence of trihydroxy bile salts and was maximal at 40 mM cholate and pH 7.5. Incubation of HepG2 cells with brefeldin A resulted in an 80 to 90% inhibition of secretion of the bile salt dependent CEH activity, while only inhibiting total protein secretion by 42%. Bile salt-dependent CEH activity could also be detected in rat liver perfusates. Although there was measurable activity in all of 14 livers analyzed (47 +/- 10 and 53 +/- 17 nmol/h per g liver per h perfusion during two 5-min collections after 15 and 30 min of perfusion, respectively), it did not correlate with the activity found in corresponding liver homogenates, as only four livers had detectable bile salt-dependent CEH activity. These results provide evidence for the secretion of a bile salt-dependent CEH activity, from both a hepatic cell line and the intact liver, that has similar properties to the enzyme previously isolated from rat liver homogenates and rat pancreas. PMID- 1627619 TI - The intracellular storage and turnover of apolipoprotein B of oxidized LDL in macrophages. AB - We have studied the effect of several chemical modifications to low-density lipoprotein (LDL) on its intracellular fate in macrophages. Native, acetylated and oxidized 125I-LDL were supplied to cultured peritoneal macrophages and the accumulation and distribution of labelled protein was measured both during uptake and a subsequent chase period. The intracellular accumulation of macromolecular oxidized LDL protein greatly exceeded that of acetylated LDL, despite similar rates of uptake and common endocytic receptors. The accumulation of intracellular apoprotein was proportional to the extent to which the LDL was first oxidized. ApoB of oxidized LDL was more resistant to proteolysis by lysosomal enzymes than native apoB. Interestingly, acetylated apoB is more rapidly hydrolysed than the native protein. 125I-LDL modified with 4-hydroxynonenal (HNE) and myricetin, but not with malondialdehyde (MDA), was also accumulated within macrophages in a high molecular weight fraction, and was resistant to cell-free lysosomal proteolysis. These forms of LDL also contained crosslinked apoB molecules. It is suggested that the accumulation of oxidized LDL within macrophages may he due, at least in part, to the formation of inter- or intra-molecular crosslinks in apoB which render it less accessible to proteolysis. PMID- 1627618 TI - Dramatic differences in lipoprotein composition among gray short-tailed opossums (Monodelphis domestica) fed a high cholesterol/saturated fat diet. AB - Lipoproteins of gray short-tailed opossums (Monodelphis domestica) were characterized to determine the basis of differences among individuals in response to a challenge diet enriched in saturated fat and cholesterol. Animals were selected from two phenotypic groups (high and low plasma cholesterol response to the challenge diet). Half of the animals in each group were fed basal diet (8.1% fat and 0.04% cholesterol by weight), and the remainder were fed challenge diet (17.7% fat and 0.61% cholesterol). The plasma cholesterol values of both groups fed the basal diet and of low responders fed the challenge diet were similar. In addition, both very-low-density and low-density lipoproteins (VLDL+LDLs) and high density lipoproteins (HDLs) were similar among these groups in density and in lipid and apolipoprotein compositions. In contrast, the high responders fed the challenge diet showed a 7-fold increase in total plasma cholesterol, which was primarily a consequence of increases in the VLDL+LDL cholesterol component defined by heparin-Mn precipitation. Moreover, the VLDL+LDLs were more heterogeneous and were characterized by decreased densities. The VLDL+LDLs of the high-responding group had higher levels of apolipoprotein (apo) B and apoE than the other groups. Plasma apoB concentrations estimated by dot blotting techniques increased by 3-fold, and apoE by 44-fold in the high responding group. Understanding the factor(s) mediating responder phenotype in this new model species will expand our knowledge of the regulation of lipemic response to diet. PMID- 1627620 TI - Antioxidant activity of xanthophylls on peroxyl radical-mediated phospholipid peroxidation. AB - The ability of xanthophylls (canthaxanthin, zeaxanthin, and astaxanthin) as chain breaking antioxidants was investigated in peroxyl radical-mediated peroxidation of phosphatidylcholine (PC) liposomes under atmospheric conditions using lipid soluble and water-soluble radical generators. These xanthophylls retarded the chain propagation reaction of phosphatidylcholine hydroperoxides (PC-OOH) formation, although their activities to trap chain-carrying peroxyl radical were much less than that of alpha-tocopherol. In chick plasma studies, it was observed that endogenious xanthophylls participated in the antioxidant defenses against the attack of aqueous peroxyl radical. It was concluded that xanthophylls possess the ability to act as chain-breaking antioxidants in the peroxidation of membraneous phospholipids. Dietary xanthophylls may, therefore, be helpful in resisting membraneous phospholipids against oxidative damage in vivo. PMID- 1627621 TI - Effect of high levels of selected dietary essential amino acids on hypercholesterolemia and down-regulation of hepatic LDL receptors in rabbits. AB - Earlier studies showed that the elevation of serum total and low density lipoprotein (LDL) cholesterol levels produced in rabbits by feeding high levels of a casein amino acid mixture in a cholesterol-free, semipurified diet was due primarily to the essential amino acids (EAA) in the mixture. Replacing all of the non-essential amino acids in the mixture by glutamic acid (45% EAA+Glu) had little effect on the hypercholesterolemia produced by the EAA. Experiments designed to identify the hypercholesterolemic EAA showed that (i) feeding high levels of ketogenic EAA only (45% EketoAA) gave a substantial but variable elevation of serum total and LDL cholesterol and (ii) feeding high levels of all EAA except arginine (45% EAA-Arg) gave a particularly strong hypercholesterolemic response. In rabbits fed the 45% EAA-Arg diet and to a lesser extent, in those fed the 45% EAA+Glu diet, EDTA-sensitive binding of 125I-LDL to hepatic membranes in vitro was reduced compared to a control, low-cholesterolemic group fed all essential and non-essential amino acids at a level corresponding to 14.7% casein, indicating that the hypercholesterolemia was associated with down-regulation of hepatic LDL receptors. PMID- 1627622 TI - Synthesis of platelet activating factor and metabolism of related lipids in embryonic cells. AB - Primary cultures of mouse embryo palate mesenchyme (MEPM) cells incubated with 1 O-[3H]alkyl-2-lyso-sn-glycero-3-phosphocholine ([3H])lyso-PAF) incorporated radiolabel into 1-radyl-2-acyl-sn-glycero-3-phosphocholine (PC) and phosphoethanolamine (PE). The radiolabeled PC was insensitive to hydrolysis with HCl fumes, whereas at least 82% of the 3H found in the PE was hydrolyzed to 3H aldehydes by such treatment. Treatment of the PC with Vitride produced [3H]alkylglycerol; similar treatment of the PE produced [3H]alk-1-enylglycerol. None of the radiolabeled products yielded fatty alcohol upon reduction with Vitride. These findings indicate the radiolabeled PC was 1-O-alkyl-linked whereas the PE contained predominantly 1-O-alk-1'-enyl species with smaller amounts of 1 O-alkyl species. Homogenates of MEPM cells which had been prelabeled with [3H]lyso-PAF and [14C]arachidonic acid produced 14C-fatty acid, [3H]lyso-PC, and [3H]alkylglycerol when incubated at selected values of pH and concentrations of calcium. There was no accumulation of [3H]lyso-PE in the various incubation mixtures. Stimulation of MEPM cells with the ionophore A23187 in the presence of calcium and [3H]acetate resulted in the production of 3H-platelet-activating factor (PAF), identified by its migration with authentic PAF and its conversion to 1-O-[3H]alkyl-2,3-diacetylglycerol upon treatment with phospholipase C and acetic anhydride. These studies demonstrate that: (i) MEPM cells are able to incorporate [3H]lyso-PAF into 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine, the storage form of PAF, and into 1-O-alk-1'-enyl-2-acyl-sn-glycero-3 phosphoethanolamine (PE plasmalogen); (ii) endogenous 1-O-[3H]alkyl-2-acyl-sn glycero-3-phosphocholine can serve as a substrate for phospholipase A2 in homogenates; and (iii) MEPM cells have the ability to synthesize PAF, thus raising the possibility that this compound may play a role in modulating the physiology of these embryonic cells. PMID- 1627624 TI - Inhibition of phospholipase A2 by cis-unsaturated fatty acids: evidence for the binding of fatty acid to enzyme. AB - Calcium-dependent phospholipases A2 are markedly inhibited in vitro by cis unsaturated fatty acids (CUFAs) and to a much lesser extent by trans-unsaturated or saturated fatty acids. Thus, CUFAs may function as endogenous suppressors of lipolysis. To better understand the mechanism of inhibition, kinetic analysis, fluorescence spectroscopy and gel permeation chromatography were employed to demonstrate that CUFAs interact with a highly purified Ca(2+)-dependent phospholipase A2 from Naja mossambica mossambica venom. Arachidonate inhibited hydrolysis of both [1-14C]oleate-labelled, autoclaved Escherichia coli and [1 14C]linoleate-labelled phosphatidylethanolamine in an apparent competitive manner. When subjected to gel permeation chromatography, [3H]arachidonate, but not [3H]palmitate, comigrated with the enzyme. Arachidonic and other CUFAs increased the fluorescence intensity of the enzyme almost 2-fold in a dose dependent fashion (50 microM = 180% of control); methyl arachidonate was without effect. Saturated fatty acids had only a modest effect on enzyme fluorescence (50 microM = 122% of control). Concentrations of arachidonate that inhibited in vitro enzymatic activity by almost 80% did not alter binding of phospholipase A2 to the E. coli substrate. Collectively, these data demonstrate that, while CUFAs selectively bind to the enzyme, they do not influence phospholipase A2-substrate interaction. Inhibition of in vitro phospholipase A2 activity by CUFAs may be mediated by the formation of an enzymatically inactive enzyme-substrate-inhibitor complex. PMID- 1627623 TI - Evidence for mechanisms of the hypotriglyceridemic effect of n-3 polyunsaturated fatty acids. AB - Ingestion of modest amounts of n-3 polyunsaturated fatty acids (PUFA) (2.8% w/w) decreased plasma triglyceride levels in Syrian hamsters by 49%. This was associated with a 45% increase in hepatic carnitine palmitoyl transferase activity. Significantly, at this low level of n-3 PUFA intake, hepatic peroxisomal oxidation measured as CN- insensitive palmitoyl-CoA dependent NAD reduction was unaffected. Consumption of increasing amounts of dietary n-3 PUFA up to 2% (w/w) in hamster diets containing 15% fat, gradually decreased plasma triglycerides to 56% of the control levels. The diet induced changes in plasma triglyceride levels were highly correlated (r = -0.97, P less than 0.01) with changes in hepatic carnitine palmitoyl transferase activity. A gradual decrease up to 59% in hepatic phosphatidate phosphohydrolase activity with n-3 fatty acid consumption was also observed. The hypotriglyceridemic effects of moderate intakes of n-3 fatty acids are, therefore, associated with changes in key enzymes in hepatic triglyceride synthesis and mitochondrial oxidation, but not peroxisomal oxidation. PMID- 1627625 TI - Metabolism in vivo of [14C]oleic acid and [3H]retinol of lipid-poor and lipid rich chyle. AB - [3H]Retinol and [14C]oleic acid labelled fresh chyle was obtained from thoracic duct cannulated rats. The labelled compounds were fed dispersed in either a small amount of egg phosphatidylcholine to produce a lipid-poor chyle, or in a soy bean lipid emulsion to produce a lipid-rich chyle. Small amounts (100 microliters, 24 and 172 micrograms triacylglycerol, respectively) of fresh labelled chyle preparations were injected i.v. into fed recipient animals, which were killed after 10, 20 or 30 min. At 20 min, more [3H]retinyl ester remained in plasma in the rats injected with lipid-rich than in those injected with lipid-poor chyle. The difference was, however, smaller than the difference in the hepatic uptake of 3H. Both the uptake of 3H by the liver and the hydrolysis of [3H]retinyl ester after the uptake, was faster in the group that had been injected with the lipid poor chyle. The 3H/14C ratios of the serum and liver lipids in relation to that of the injected material did not differ between the two groups, indicating that the proportion of the [14C]triacylglycerol that underwent hydrolysis before clearance of remnants by the liver did not differ. Particularly in the heart, but also in adipose tissue, lungs and kidneys the 3H radioactivity after injecting lipid-rich chyle was highest at 10 min and then decreased with time, being similar in the two groups at 30 min. The results suggest that the formation of remnants from lipoproteins formed after a fat meal requires a longer time for the interaction with endothelial-bound lipoprotein lipase. The uptake by the spleen was also 6-9-fold higher than in the group receiving lipid-poor chyle, indicating that the reticuloendothelial system participates in the metabolism of chyle lipoproteins after a fat meal. PMID- 1627627 TI - Identification of 7 alpha-hydroxy-3-oxo-4-cholestenoic acid in chronic subdural hematoma. AB - We detected a novel kind of bile acid in the content of chronic subdural hematoma. This substance was specifically found in chronic subdural hematoma, and not in subdural hygroma, which is pathologically similar except for the lack of capsular membrane. The compound was identified as 7 alpha-hydroxy-3-oxo-4 cholestenoic acid by high performance liquid chromatography, gas chromatography mass spectrometry, and nuclear magnetic resonance spectrometry. The structure was confirmed by the comparison with the chemically synthesized compound. The average contents in chronic subdural hematoma were 658.09 +/- 137.53 ng/ml, while those in normal human plasma were 126.27 +/- 17.73 ng/ml. It was not detected in normal cerebrospinal fluid. The higher level in chronic subdural hematoma than human plasma strongly suggests the local, extrahepatic production of this type of C27 bile acids. PMID- 1627626 TI - Biosynthesis and chemical synthesis of carboxyl-linked glucuronide of lithocholic acid. AB - The glucuronidation of lithocholic acid (LA) by phenobarbital-induced male Fischer 344 rat liver microsomes supplemented with UDP-glucuronic acid was studied. A single radioactive metabolite was formed and its structure was determined by high pressure liquid chromatography/particle beam/mass spectrometry (HPLC/PB/MS), both with and without prior methylation and acetylation of the sample. The reaction product was rigorously identified as the 1-O-acyl-beta-D glucuronide of LA by comparison with a chemically synthesized standard. The chemical synthesis of the acyl glucuronide of LA was accomplished via a condensation reaction using benzyl 2,3,4-tri-O-benzyl-D-glucopyranuronate. The latter compound was prepared in two steps from benzyl 2,3,4-tri-O-benzyl-1-O methyl-alpha-D-glucopyranuronate via the 1-O-acetyl derivative. The stereoselective beta coupling of LA with 2,3,4-tri-O-benzyl-D-glucopyranuronate was achieved by the Mitsunobu reaction, in the presence of the free hydroxyl function of LA, using triphenylphosphine and diisopropyl azodicarboxylate in THF followed by preparative TLC. The benzylic ester and ether groups were cleaved by hydrogenation with Pd on charcoal as the catalyst. Positive identification of the glucuronide was established by HPLC/PB/MS and 1H-NMR spectra. No side products formed by acyl migration were detected, but the free acyl glucuronide underwent rapid transesterification in methanol. PMID- 1627628 TI - Reversibility of the effects of dietary fish oil on the fatty acid composition of the brain and retina of growing chicks. AB - Dietary fish oil increases levels of (n-3) fatty acids in the brain and retina of younger animals but has less effect in adults. The duration of the effects of fish oil in young animals, as well as the extent of reversibility of the effects, are unknown. Laying hens were fed either a fish oil diet or a soybean oil-based control diet. Resulting chicks were assigned to three diet groups: chicks from fish oil and soybean oil hens were continued on fish oil and soybean oil diets, respectively, for 0, 3, 6, or 9 weeks, and additional chicks from the fish oil hens were fed the fish oil diet for 0, 3, or 6 weeks and then reversed to the soybean oil diet for a period of 3 weeks. The fatty acid composition of the brain, retina, liver, and serum of the reversal chicks was compared with chicks fed the fish oil diet only or the soybean oil diet only. Brain levels of docosahexaenoic acid (22:6(n-3)) decreased substantially when reversal from the fish oil diet to the control diet was begun at hatching, but did not decrease when reversal was begun at later times. Other (n-3) fatty acids in the brain, docosapentaenoic acid (22:5(n-3)) and eicosapentaenoic acid (20:5(n-3)), decreased substantially at all ages, and to a greater extent than 22:6(n-3). Brain arachidonic acid (20:4(n-6)), which was low in fish oil chicks, rose to control after reversal at hatching, but recovered only partially when reversal was begun at later times. A similar patterns was observed in the retina. Serum and liver (n-3) fatty acids fell to control in all reversal chicks, and (n-6) fatty acids increased to control, except in chicks reversed at 6 weeks. This study demonstrates that by 3 weeks of age the chick brain strongly resists diet induced lowering of high levels of 22:6(n-3). PMID- 1627629 TI - Emerging role of lipids of Candida albicans, a pathogenic dimorphic yeast. AB - It is clear that C. albicans lipids have gained tremendous importance in recent years. In addition to being a barrier for entrance of various metabolites, it also provides the site of action for the synthesis of enzyme(s) involved in cell wall morphogenesis and antifungal action. While alterations in lipid composition during a yeast to mycelia transition have been observed, in most of the studies, lipid fluctuations reported could have been due to various environmental factors involved in the induction of morphogenesis [4,5]. A clear understanding of lipid biosynthesis and metabolic blocks due to antifungal action is likely to shed further light on selective interactions of antifungals. Despite the multifacet role of lipids in various functions of this pathogenic yeast, their exact involvement is poorly understood. The situation is little better with regard to ergosterol and its metabolism. Ergosterol is, indeed, important for anti-candidal activity and appears to be involved in the morphogenesis of C. albicans. The fluctuation in phospholipid composition have led to altered properties of plasma membrane namely, membrane fluidity, transport activities and drug sensitivity, which suggest that-a critical level of individual phospholipid is important for proper functioning of the plasma membrane. What the exact role is of individual phospholipid is far from clear. Many unanswered questions relating to the role of PI and sphingomyelin in signal transduction, involvement of phospholipases in the maintenance of phospholipid composition, and role of lipid transfer proteins in assembly and asymmetry of lipids are some aspects which merit further work. PMID- 1627630 TI - Tetrahydropyran ring-containing fatty acid-combined taurine (tetrathermoyltaurine) in the taurolipid fraction of Tetrahymena thermophila. AB - A tetrahydropyran ring-containing fatty acid-combined taurine (tetrathermoyltaurine) was found in the taurolipid fraction of Tetrahymena thermophila. Tetrathermoyltaurine accounted for about 0.6% of the total taurolipid of the cells. The compound was subjected to methanolic hydrochloric acid hydrolysis, and the structures of the hydrolysis products were identified by nuclear magnetic resonance and mass spectrometries, as taurine and 2,3-dihydroxy 9,13-oxy-7-trans-octadecenoic acid (tetrathermic acid). The chemical structure of tetrathermoyltaurine was identified as 2-(2,3-dihydroxy-9,13-oxy-7-trans octadecenoylamino) ethanesulfonic acid. This structure suggests that tetrathermoyltaurine may be derived from taurolipid B as the major taurolipid of the cells. When cells of HL 60, as a human lymphoma, were cultured with tetrathermoyltaurine, 88% of the cell growth was inhibited at the concentration of 100 micrograms/ml. PMID- 1627631 TI - Human peripheral lymph lipoproteins are enriched in sphingomyelin. AB - The concentrations of total choline-containing phospholipids and of sphingomyelin have been determined in peripheral lymph from six volunteers. The concentration in lymph of total phospholipids was 14.6 +/- 6.0 mg/dl and of sphingomyelin 6.1 +/- 2.7 mg/dl; the estimated concentration of phosphatidylcholine (by subtracting the concentration of sphingomyelin from that of total choline-containing lipoproteins) was 8.5 +/- 5.1 mg/dl. The concentration of free choline in lymph was less than 1 mg/dl. The ratio of the concentration in lymph to that in the subject's own plasma of sphingomyelin was 0.18 +/- 0.07 and that of (estimated) phosphatidylcholine 0.05 + 0.04; the difference between these two ratios was significant at P less than 0.002. The present data are compatible with the hypothesis that some of lipoprotein phosphatidylcholine is lost while crossing from plasma to lymph. PMID- 1627632 TI - Differences in the interconversion between 20- and 22-carbon (n - 3) and (n - 6) polyunsaturated fatty acids in rat liver. AB - When male weanling rats were fed diets containing either 5% corn oil or a diet in which half of the corn oil was replaced by fish oil, the 20:5(n - 3) in liver choline and ethanolamine phosphoglycerides, not only partially replaced arachidonate but also paired with palmitic and stearic acids in the same molar ratio as did arachidonate. The 22:5(n - 3)/22:6(n - 3) ratio in the liver phospholipids of corn oil fed rats was similar to that found when the esterified levels of these two acids were increased 5-fold by feeding fish oil. Moreover, the pairing of both 22:5(n - 3) and 22:6(n - 3) with palmitic and stearic acids, on a molar ratio basis, was relatively independent of the total amount of esterified 22:5(n - 3) and 22:6(n - 3). When (3-14C)-labeled 22:4(n - 6) was injected into rats raised on a chow diet or incubated with hepatocytes from these animals, its primary metabolic fate was retroconversion to arachidonate followed by esterification. Conversely, [3-14C]22:5(n - 3) was a poorer substrate for retroconversion with a larger amount being esterified directly into phospholipids and, in addition, this acid served as a precursor for 22:6(n - 3). The enhanced metabolism of both [3-14C]22:4(n - 6) to 22:5(n - 6) and of [3-14C]22:5(n - 3) to 22:6(n - 3) in animals raised on a diet devoid of fat or in their hepatocytes may possibly be due to elevated 6-desaturase activity and/or the level of this enzyme or enzymes. This hypothesis is based on studies showing that the synthesis of 22:6(n - 3) proceeds via a pathway independent of a 4-desaturase but requires the use of a 6-desaturase at two steps (Voss, A., Reinhart, M., Sankarappa, S. and Sprecher, H. (1991) J. Biol. Chem. 266, 19995-20000). PMID- 1627633 TI - Incorporation of new amphiphilic perfluoroalkylated bipyridine platinum and palladium complexes into liposomes: stability and structure-incorporation relationships. AB - New perfluoroalkylated side-chain (formed by a perfluoroalkyl tail grafted onto a hydrocarbon spacer) bipyridine complexes of platinum, palladium and their hydrocarbon analogs, when dispersed in aqueous solutions in the presence of egg yolk phospholipids (EYP), are incorporated into EYP vesicles. Most complexes retain their chemical and structural integrity when entrapped into liposomes, thermally sterilized under the FDA norms and stored for 3 months at 25 degrees C. All complex/liposome preparations consist mainly of small unilamellar vesicles (size less than 100 nm) together with a population of larger uni- or multilamellar vesicles (100 to 230 nm). These preparations are remarkably stable with respect to particle size and size distribution evolution and complex leakage: no precipitate of drug was detected even after 7 months of storage at 25 degrees C. The impact of the perfluoroalkyl tail and of the other structural features of the complexes on their incorporation efficiency into EYP liposomes is assessed. A high fluorophilic character (long perfluoroalkyl tail), when tempered by an equally lipophilic one (long hydrocarbon spacer) is not detrimental to the incorporation efficiency of a perfluoroalkylated drug into hydrocarbon vesicles. This incorporation efficiency is considerably improved by the introduction of a double bond between the perfluoroalkyl tail and the hydrocarbon spacer, forming the bipyridine side-chains. PMID- 1627634 TI - Regulation of HMG-CoA reductase, apoprotein-B and LDL receptor gene expression by the hypocholesterolemic drugs simvastatin and ciprofibrate in Hep G2, human and rat hepatocytes. AB - The comparative effects of simvastatin (a competitive inhibitor of HMG-CoA reductase) and ciprofibrate (another inhibitor of cholesterogenesis) on the incorporation of [14C]acetate and [3H]mevalonate into cholesterol HMG-CoA reductase activity, apo-B synthesis, LDL receptor, and their corresponding mRNAs, have been studied in the human hepatoma cell line Hep G2 and in human and rat hepatocytes in primary culture. Incubation of Hep G2 with simvastatin (0.01-1.5 microM) or ciprofibrate (25-100 microM) produced not only a marked inhibition of cholesterogenesis from [14C]acetate but also from [3H]mevalonate, an intermediate downstream of the HMG-CoA reductase reaction. However, in human and rat hepatocytes, cultured in similar conditions, simvastatin inhibited only the cholesterol synthesis from [14C]acetate, as expected. HMG-CoA reductase activity was greatly induced in Hep G2 and rat hepatocytes after incubation with simvastatin (up to 400% of controls), but not with ciprofibrate. Increased enzyme activity was accompanied by a higher cell content of reductase mRNA. Apo-B concentration in the medium of Hep G2 cells was 31% lower after 31 h incubation with simvastatin than in controls. However, neither simvastatin nor ciprofibrate modified the synthesis rate of apo-B or its mRNA level. Both LDL-receptor and its mRNA levels were raised by simvastatin at concentrations inhibiting cholesterol synthesis. Our data show that, in this human hepatoma cell line, HMG-CoA reductase competitive inhibition by simvastatin triggers a coordinate regulation of the expression of genes coding for reductase and LDL receptor but not for apo B. Ciprofibrate, though efficient in inhibiting cholesterogenesis, did not induce the same regulatory reactions. The reason for this discrepancy is unknown. PMID- 1627635 TI - Plasma clearance of model lipoproteins containing saturated and polyunsaturated monoacylglycerols injected intravenously in the rat. AB - Triacylglycerols, with a saturated long-chain fatty acid at the glycerol-2 position, slow the clearance from plasma of remnants derived from injected chylomicrons and chylomicron-like emulsions. Slowing of remnant clearance also occurs when about 1% of monostearoylglycerol is added to a triolein chylomicron like emulsion. We have now found that addition of monoacylglycerols, containing a saturated acyl chain from 12 to 20 carbons, slowed the plasma clearance and decreased the liver uptake of the remnants. In contrast, monoacylglycerols with unsaturated acyl chains were inconsistent in their effects on the remnant clearance. Monoarachidonin (M20:4) slowed remnant clearance comparable to that of saturated monoacylglycerols, monolinolenin (M18:3) and monolinolein (M18:2) were less effective, while monoolein had the least effect on remnant clearance. We have confirmed the defective remnant clearance in rats of injected emulsions containing saturated acyl chain by the using the diester-2-ether analogues of triolein and 1,3-dioleoyl-2-stearoylglycerol (OSO). Chylomicron-like lipid emulsions made with the ether analogues had clearance rates similar to their triester counterparts. Preformed remnants derived from emulsions of OSO, its ether analogue, and triolein emulsions or emulsions of triolein with approximately 1% saturated monoacylglycerols were prepared in hepatectomized rats. After intravenous injection into conscious recipient rats, these remnants were cleared from plasma similar to remnants traced in situ by lipolysis of injected chylomicron-like emulsions. PMID- 1627636 TI - Inhibition of cellular transport systems by alkyl phospholipid analogs in HL-60 human leukemia cells. AB - Specific non-metabolizable alkyl-phospholipids selectively kill neoplastic cells, yet normal and more differentiated cells are relatively resistant. Although these highly selective anticancer lipids appear to target the cell membrane, their mechanism of cytotoxic action remains to be defined. We report here that treatment of 'sensitive' HL-60 leukemia cells with one of the most potent lipid agents, 1-alkyl-2-methoxy-glycero-3-phosphocholine, inhibits the cellular transport of multiple essential nutrients including choline, amino acids, fatty acids, and the non-metabolizable carbohydrate, 2-deoxy-D-glucose. Minimal inhibitory responses of the varied transport systems were noted in HL-60 cells treated with the less potent, 2-lyso analog, and in 'resistant' K562 leukemia cells, treated with the 2-methoxy lipid. Although both the 2-methoxy lipid and 12 tetradacanoylphorbol 13-acetate induce differentiation in HL-60 cells, significant differences in the interactions of these lipids on cellular choline transport were found. Based on these results, we conclude that multiple nutrient deprivation induced by the detergent-like action of the methoxy-containing alkyl phospholipid results in the selective destruction of neoplastic cells that are sensitive to this membrane-targeted antitumor agent. PMID- 1627637 TI - Tissue lipid accumulation by L-aminocarnitine, an inhibitor of carnitine palmitoyltransferase-2. Studies in intact rats and isolated mitochondria. AB - Tissues of fasted animals treated with L-aminocarnitine (L-3-amino-4 trimethylaminobutyrate) showed an accumulation of long-chain acylcarnitines and triacylglycerols. Blood levels of free fatty acids, long-chain acylcarnitines and triacylglycerol-rich lipoproteins were found to be increased, whereas glucose was reduced. The liver mitochondria isolated from rats treated with L-aminocarnitine utilized both pyruvate and succinate normally, but were not able to oxidize palmitoylcarnitine. In vitro oxidation of palmitoylcarnitine by liver mitochondria was inhibited by L-aminocarnitine in a concentration-dependent fashion in contrast to succinate and pyruvate oxidation which was not modified. L aminocarnitine proved to be a potent and selective inhibitor (IC50 = 805 nM) of the carnitine palmitoyltransferase isoenzyme, located on the inner side of the mitochondrial inner membrane (CPT2). The activity of the carnitine palmitoyltransferase isoenzyme located on the mitochondrial outer membrane inhibitable by malonyl-CoA (IC50 = 19 microM), was not inhibited by 0.8 microM L aminocarnitine. Both in vitro and in vivo effects of L-aminocarnitine suggest that the substance has a specific and potent inhibitory action on CPT2. Its in vivo inhibition results in a dramatic increase of long-chain acylcarnitines in various organs, that it is why this increase can be considered a very good marker of CPT2 inhibition. A markedly altered lipid metabolism was observed. PMID- 1627638 TI - Physical evidence for the presence of two forms of phosphatidate phosphohydrolase in rat liver. AB - Phosphatidate phosphohydrolase (PAP)-catalysed dephosphorylation of phosphatidic acid to diacylglycerol is an important step in glycerolipid metabolism and cell signalling. Gel filtration chromatography on Superose 6 and anion-exchange chromatography on Mono Q of rat liver subcellular fractions has provided physical evidence for the presence of two distinct forms of PAP activity. One form was sensitive to inhibition by N-ethylmaleimide (NEM), had an apparent M(r) of 540,000 and was eluted from the anion-exchange column by 0.35 M NaCl, while the other was insensitive to inhibition by NEM, had an apparent M(r) of 240,000 and was eluted from the anion-exchange column by 0.15 M NaCl. Studies on the subcellular distribution of these two enzymes, using 5'-nucleotidase as a plasma membrane marker, demonstrated that the NEM-sensitive form was predominantly cytosolic but translocated to the microsomal membranes in response to oleate. The NEM-insensitive form was predominantly located in the plasma membrane but a small proportion (approx. 10%) of total cell activity was present on the endoplasmic reticulum. The implications of these results for the likely roles of the two different forms of PAP in fatty acid esterification and cell-signalling are discussed. PMID- 1627639 TI - Endothelial EA.hy 926 cells can be loaded with cationized LDL, but not with acetylated LDL. AB - EA.hy 926 cells, a human endothelial cell line, show characteristics of differentiated endothelial cells. Endothelial cells normally express membrane scavenger receptors. Therefore modified LDL, eg., acetylated LDL, can be taken up, causing accumulation of mass amounts of cholesterol. We have shown that EA.hy 926 cells cannot be loaded with cholesterol using acetylated LDL, but can be efficiently enriched with cholesterol by incubation with cationized LDL. The loaded cells may serve as models for studies on reverse cholesterol transport. PMID- 1627640 TI - Base-exchange and cell growth in 3T6 mouse fibroblasts. AB - Synthesis of phosphatidyl serine by base-exchange and DNA synthesis both declined rapidly in mouse fibroblast cultures upon withdrawal of serum from nutrient medium. Base-exchange returned to control levels within 3 h after the addition of serum, while DNA synthesis lagged by 10 h. Phosphatidyl serine synthesis is thus an early response of 3T6 cells to mitogenic signals. PMID- 1627641 TI - Subcellular distribution and activity of glucose transporter isoforms GLUT1 and GLUT4 transiently expressed in COS-7 cells. AB - In adipose and muscle cells, the glucose transporter isoform GLUT4 is mainly located in an intracellular, vesicular compartment from which it is translocated to the plasma membrane in response to insulin. In order to test the hypothesis that this preferential targeting of a glucose transporter to an intracellular storage site is conferred only by its primary sequence, we compared the subcellular distribution of the fat/muscle glucose transporter GLUT4 with that of the erythrocyte/brain-type glucose transporter GLUT1 after transient expression in COS-7 cells. Full-length cDNA was ligated into the expression vector pCMV that is driven by the cytomegalovirus promoter, and introduced into COS cells by the DEAE-dextran method. Cells were homogenized and fractionated by differential centrifugation to yield plasma membranes and a Golgi-enriched fraction of intracellular membranes (low-density microsomes). In these membrane fractions, the abundance of glucose transporters was assessed by immunoblotting with specific antibodies against GLUT1 and GLUT4, and their transport activity was assayed after solubilization and reconstitution into lecithin liposomes. Uptake rates of 2-deoxyglucose assayed in parallel samples were higher in cells expressing GLUT1 or GLUT4 as compared with control cells (transfection of pCMV without transporter cDNA). Reconstituted glucose transport activity in plasma membranes was about 5-fold higher after expression of GLUT1 and GLUT4 as compared with control cells. The relative amount of GLUT4 in the low-density microsomes as detected by reconstitution and immunoblotting exceeded that of the GLUT1, but was much lower than that observed in typical insulin-sensitive cells, e.g., rat fat cells or 3T3-L1 adipocytes. These data indicate that COS-7 cells transfected with glucose transporter cDNA express the active transport proteins and can be used for functional studies. PMID- 1627642 TI - The strain-dependent constitutive expression of murine serum amyloid-P component is regulated at the transcriptional level. AB - The strain-dependent expression of murine serum amyloid P-component (SAP) has been known to be linked to the Sap locus. We have quantified the SAP mRNA in several inbred strains including DBA/2 and C57BL/6 mice which represent high and low producers of SAP at resting state, respectively, and found that the mRNA levels correlated well with the amount of SAP protein. Interestingly, the SAP mRNA level of F1 mouse between DBA/2 and C57BL/6 was low and similar to that of C57BL/6. Primer extension and ribonuclease (RNAase) protection analyses demonstrated that a single type of transcript was generated from the SAP gene and that the cap sites were identical regardless mouse strains tested under unstimulated and stimulated (by lipopolysaccharide (LPS) or interleukin-6 (IL-6)) conditions. To investigate possible structural difference of the SAP gene including 5' flanking region, we have cloned, sequenced and compared the SAP genes from DBA/2 and C57BL/6 mice. Sequence analyses revealed that the 5' flanking regulatory regions, as well as the coding regions, were well-conserved between the two strains. These results demonstrate that the strain-dependent SAP expression occurs at the transcriptional level but seems to be affected by neither different type of the transcripts nor structural difference of the 5' flanking and coding regions of the SAP gene. It was suggested that a possible transcription factor with suppressive activity, which is encoded by a gene linked to Sap, may be involved. PMID- 1627643 TI - Neonatal extinction of liver lipoprotein lipase expression. AB - In contrast to the complete absence of lipoprotein lipase (LPL) mRNA in adult rat liver, fetal and neonatal rat liver contain substantial amounts of LPL mRNA, which is translated in active LPL protein as can be deduced from the presence of LPL activity in this organ. At this neonatal stage, both the relative abundance of LPL mRNA and LPL activity increased with starvation. During the suckling period, LPL mRNA and LPL activity gradually decreased until both parameters were undetectable. While the administration of L-thyroxine or hydrocortisone enhanced the disappearance of LPL mRNA, induced hypothyroidism delayed its disappearance. In adult animals induced hypothyroidism could not reactivate LPL mRNA production in the liver. The data presented suggest that liver LPL production responds to changes in the nutritional state and becomes extinguished during development, in a fashion reminiscent to the extinction of alpha-fetoprotein. This extinction of LPL gene expression is influenced by hormonal factors. PMID- 1627644 TI - cDNA cloning, sequencing, expression and possible domain structure of human APEX nuclease homologous to Escherichia coli exonuclease III. AB - cDNA encoding the human homologue of mouse APEX nuclease was isolated from a human bone-marrow cDNA library by screening with cDNA for mouse APEX nuclease. The mouse enzyme has been shown to possess four enzymatic activities, i.e., apurinic/apyrimidinic endonuclease, 3'-5' exonuclease, DNA 3'-phosphatase and DNA 3' repair diesterase activities. The cDNA for human APEX nuclease was 1420 nucleotides long, consisting of a 5' terminal untranslated region of 205 nucleotide long, a coding region of 954 nucleotide long encoding 318 amino acid residues, a 3' terminal untranslated region of 261 nucleotide long, and a poly(A) tail. Determination of the N-terminal amino acid sequence of APEX nuclease purified from HeLa cells showed that the mature enzyme lacks the N-terminal methionine. The amino acid sequence of human APEX nuclease has 94% sequence identity with that of mouse APEX nuclease, and shows significant homologies to those of Escherichia coli exonuclease III and Streptococcus pneumoniae ExoA protein. The coding sequence of human APEX nuclease was cloned into the pUC18 SmaI site in the control frame of the lacZ promoter. The construct was introduced into BW2001 (xth-11, nfo-2) strain and BW9109 (delta xth) strain cells of E. coli. The transformed cells expressed a 36.4 kDa polypeptide (the 317 amino acid sequence of APEX nuclease headed by the N-terminal decapeptide derived from the part of pUC18 sequence), and were less sensitive to methylmethanesulfonate and tert-butyl-hydroperoxide than the parent cells. The N-terminal regions of the constructed protein and APEX nuclease were cleaved frequently during the extraction and purification processes of protein to produce the 31, 33 and 35 kDa C-terminal fragments showing priming activities for DNA polymerase on acid depurinated DNA and bleomycin-damaged DNA. Formation of such enzymatically active fragments of APEX nuclease may be a cause of heterogeneity of purified preparations of mammalian AP endonucleases. Based on analyses of the deduced amino acid sequence and the active fragments of APEX nuclease, it is suggested that the enzyme is organized into two domains, a 6 kDa N-terminal domain having nuclear location signals and 29 kDa C-terminal, catalytic domain. PMID- 1627645 TI - Secondary (non-GpC) binding sites for actinomycin on DNA. AB - Actinomycin D has long been known to bind selectively to the dinucleotide step GpC. We have investigated its ability to bind to other non-canonical sequences using a series of synthetic DNA fragments. DNase I footprinting experiments reveal that actinomycin can also bind well to GG (CC). Binding to this sequence and the canonical GC site is potentiated by flanking regions of (GT)n.(AC)n. Weaker but specific binding to GT and AC is also evident and appears to be cooperative. PMID- 1627646 TI - A rapid procedure for production of human basic fibroblast growth factor in Escherichia coli cells. AB - Human basic fibroblast growth factor has been expressed in Escherichia coli cells at a level of 2-3 mg/l culture, using a rapid procedure which requires only simple DNA manipulative work. The recombinant material has the same potency as natural basic fibroblast growth factor from bovine pituitary glands. PMID- 1627647 TI - Cationic liposomes enhance targeted delivery and expression of exogenous DNA mediated by N-terminal modified poly(L-lysine)-antibody conjugate in mouse lung endothelial cells. AB - A new and improved system for targeted gene delivery and expression is described. Transfection efficiency of N-terminal modified poly(L-lysine) (NPLL) conjugated with anti-thrombomodulin antibody 34A can be improved by adding to the system a lipophilic component, cationic liposomes. DNA, antibody conjugate and cationic liposomes form a ternary electrostatic complex which preserves the ability to bind specifically to the target cells. At the same time the addition of liposomes enhance the specific transfection efficiency of antibody-polylysine/DNA binary complex by 10 to 20-fold in mouse lung endothelial cells in culture. PMID- 1627648 TI - PCR cloning and nucleotide sequence determination of the 18S rRNA genes and internal transcribed spacer 1 of the protozoan parasites Cryptosporidium parvum and Cryptosporidium muris. AB - The genes encoding 18S rRNA and internal transcribed spacer 1 (1TS1) of Cryptosporidium parvum and Cryptosporidium muris were amplified from oocysts by PCR utilizing primers complementary to conserved regions of the 5' end of 18S and 5.8S rRNA. PCR products were cloned and the complete nucleotide sequences of two clones of each Cryptosporidium species were determined. The 18S rRNA genes of C. parvum and C. muris showed more than 99% sequence identity. PMID- 1627649 TI - The primary structures of the flavodoxins from two strains of Desulfovibrio gigas. Cloning and nucleotide sequence of the structural genes. AB - The structural genes coding for the flavodoxin proteins from two different strains of the sulfate-reducing bacteria Desulfovibrio gigas (ATCC 19364/NCIB 9332 and ATCC 29494/DSM 496) have been identified, cloned and the nucleotide sequence established. The protein sequences derived from the gene from each strain share a sequence identity of 66% with regions directly involved in binding the flavin mononucleotide cofactor being the most homologous. Both aromatic residues that flank the flavin isoalloxazine ring in the crystal structure of the flavodoxin from D. vulgaris, i.e., Trp-60 and Tyr-98, are also present in these flavodoxin proteins. These observations stand in contrast to reports that the flavodoxin from Desulfovibrio gigas contains a single tryptophan residue which is located distant from the flavin binding site. Therefore, the FMN binding site of this flavodoxin is not distinct from the other Desulfovibrio flavodoxins in this regard. PMID- 1627650 TI - The cDNA cloning and mRNA expression of rat protein C. AB - We cloned a cDNA coding for rat protein C, which provides hybridization probes for the detection of protein C mRNA in several tissues. The cloned cDNA was 1543 bp long and contained a single open reading frame of 1383 nucleotides. The proposed rat protein C precursor contained 461 amino acid residues: a 41 amino acid preproleader sequence, and light (155 amino acids) and heavy (263 amino acids) chains joined by a Lys-Arg dipeptide. Northern blot analysis showed that the rat protein C mRNA was expressed not only in the liver, but also in the kidney. PMID- 1627651 TI - Cloning and nucleotide sequence of the Vibrio proteolyticus aminopeptidase gene. AB - The gene encoding the Vibrio proteolyticus aminopeptidase was cloned and sequenced and its amino acid sequence was deduced. The gene encodes a 54 kDa protein, larger than the previously reported size of 30 kDa for the purified aminopeptidase. Sequence alignments revealed a 43-45% homology with two other Vibrio sp. extracellular proteinases. PMID- 1627652 TI - The isolation and characterization of rabbit motilin precursor cDNA. AB - The cDNA sequence of rabbit motilin precursor has been determined. The predicted amino acid sequence indicates that the precursor consists of 133 amino acids and includes a 25 amino acid signal peptide followed by the 22 amino acid motilin sequence and an 86 amino acid motilin associated peptide (MAP). As in the human and porcine precursors, two lysine residues follow motilin in the rabbit sequence. Rabbit motilin shares 64% amino acid sequence identity with human and porcine motilin, and all amino acid substitutions represent conservative changes. Amino acid sequence alignments of the rabbit, human and porcine MAP sequences suggest three functional/structural motifs corresponding to a putative endoproteinase recognition site, a putative PEST site and a potential posttranslational processing recognition element. PMID- 1627653 TI - Gene for 17 alpha-hydroxylase/C (17-20) lyase P-450: complete nucleotide sequence of the porcine gene and 5' upstream sequence of the rat gene. AB - We describe the isolation and characterization of a full-length clone for the porcine 17 alpha-hydroxylase/C(17-20) lyase (CYP17) gene. The complete exon and partial intron sequences are presented including approx. 1000 bp of the 5' upstream sequence. In addition we describe the isolation and characterization of the 5' upstream region of the rat CYP17 gene. The sequences of the first exon, part of the first intron, and approx. 3.5 kb of the 5' upstream region are presented. PMID- 1627654 TI - Primary sequence of -1436 to +53 bp of the rat preproenkephalin gene putative Z DNA and regulatory motifs. AB - We report novel sequence data extending -1436 bases 5' of the rat proenkephalin gene start site known as E4. We noted an interesting stretch of 58 bases of alternating pyrimidines that lies immediately adjacent to 71 bases of an alternating purine-pyrimidine Z-DNA-like sequence that lies between -694 bp and 566 bp. Multiple sequence homologies to putative cis-acting regulatory factor binding sites were identified by a computer aided sequence search. PMID- 1627655 TI - Molecular basis of 3-ketothiolase deficiency: identification of an AG to AC substitution at the splice acceptor site of intron 10 causing exon 11 skipping. AB - 3-Ketothiolase deficiency (3KTD) is the result of a deficiency in mitochondrial acetoacetyl-CoA thiolase (T2). The molecular basis of 3KTD was analyzed in a patient (GK10) and his family at the protein, cDNA and gene levels. Protein analyses showed that GK10's T2 protein was undetectable in fibroblasts even with the pulse-protein labeling method and that his parents were carriers of 3KTD. Complementary DNA analyses with PCR showed that T2 cDNA in the patient lacked the normal exon 11 sequence and that his parents were obligatory carriers of the DNA sequence which canceled exon 11. When the PCR-amplified genomic fragments around exon 11 were sequenced, an AG to AC mutation at the 3' splice site of intron 10 was detected. This mutation is presumed to be responsible for exon 11 skipping. PMID- 1627656 TI - Assay for L-pipecolate oxidase activity in human liver: detection of enzyme deficiency in hyperpipecolic acidaemia. AB - A direct assay method is described for L-pipecolate oxidase. The assay uses NaHSO3 to trap the L-alpha-amino [3H]adipate delta-semialdehyde (AAS) formed as a direct reaction product of L-pipecolate oxidase from L-[3H]pipecolic acid. The adduct so formed was separated from the substrate on Dowex 50 (H+) column. The product was identified as [3H]AAS by amino acid analysis after breaking down the adduct by boiling under acidic conditions. The assay is simpler and more specific than fluorometric methods; it is also more sensitive, requiring at most 16 micrograms of liver peroxisome-enriched protein per assay. We have used this assay procedure to detect L-pipecolate oxidase in skin fibroblasts obtained from a control subject and from patients of hyperpipecolic acidaemia and Zellweger syndrome and found that this enzyme activity is present in the control, but absent or decreased in the patients with the peroxisomal disorders. PMID- 1627657 TI - Restoration of mitochondrial energy-linked reactions following dexamethasone treatment of rats infected with the liver fluke Fasciola hepatica. AB - Mitochondria isolated from male Wistar rats experimentally infected with the common liver fluke, Fasciola hepatica, exhibit loss of respiratory control from 2 weeks post-infection (Rule, et al. (1989) Biochem. J. 260, 517-523). We now report that subcutaneous injections of the anti-inflammatory drug, dexamethasone, during the final week of infection prevented the mitochondrial uncoupling and restored respiratory control almost to the levels of uninfected controls. Further investigations have shown that mitochondria from infected rat livers are unable to synthesize ATP and that abnormal respiration is also evident in hepatocytes isolated from infected rats. These abnormalities were absent when infected rats were treated with dexamethasone. In addition, liver mitochondrial function in infected, congenitally athymic, nude rats (CBH/R nu/nu) was not significantly different from that in uninfected nude or Wistar controls. These results provide evidence that the mitochondrial dysfunction in fascioliasis is host-mediated and that T lymphocytes in particular may be involved. PMID- 1627658 TI - Tissue-selective action of pravastatin due to hepatocellular uptake via a sodium independent bile acid transporter. AB - Pravastatin is a foreign substrate of a sodium-independent transport system for bile acids. The tissue selectivity of pravastatin in inhibiting 3-hydroxy-3 methyl-glutaryl-coenzyme A reductase is due to the uptake via a transport system which exists predominantly in liver cells. Pravastatin competitively inhibits the sodium-independent hepatocellular uptake of cholate, taurocholate and ouabain, whereas the total uptake of cholate is non-competitively blocked. The affinity of pravastatin to the sodium-dependent taurocholate transporter is, however, low. Millimolar concentrations of pravastatin are needed to inhibit the sodium taurocholate cotransporter. Pravastatin has no affinity to other transport systems in liver cells such as those for long-chain fatty acids, amino acids, rifampicin and bivalent organic cations. PMID- 1627659 TI - Calpain II induced insolubilization of lens beta-crystallin polypeptides may induce cataract. AB - Addition of calpain II (EC 3.4.22.17) to soluble proteins from 10-day-old rat lens caused an increase in turbidity and production of water-insoluble protein. The insolubilization increased with higher concentrations of both lens protein and calpain II, it could be prevented by the cysteine protease inhibitor E-64; it required at least 0.5 mM Ca2+, it was limited to 6% of the soluble protein present and resulted from precipitation of proteolyzed beta-crystallin polypeptides. When compared by two-dimensional electrophoresis, the insoluble beta-crystallin polypeptides produced by calpain II were similar to insoluble beta-crystallin polypeptides found in cataractous lenses. Trypsin also caused insolubilization of beta-crystallin polypeptides, but these polypeptides were unlike polypeptides produced during cataract formation. These data suggested that the loss of solubility was due to a specific removal of N/or C-terminal extensions from beta-crystallin polypeptides by calpain II, and that a similar process may occur in vivo during cataract formation. It is hypothesized that the insoluble protein produced by calpain II causes cataract by increasing light scatter in the lens. PMID- 1627660 TI - Induction of hepatic and pulmonary caeruloplasmin gene expression in developing guinea pigs following premature delivery. AB - We have previously shown that mRNA for caeruloplasmin, the serum copper-binding protein, is not expressed in guinea-pig liver prior to birth and expression increases rapidly following parturition. To further study the regulation of caeruloplasmin in neonatal animals we have used 3-day preterm guinea pigs, delivered by caesarean section, to investigate mRNA expression in liver and lung. Within 12 h of premature birth, hepatic caeruloplasmin mRNA levels are significantly increased and remain elevated by 72 h. This induction of expression is accompanied by an increase in circulating levels of holoprotein. Even greater induction of caeruloplasmin mRNA was observed in premature animals maintained in 95% oxygen for 72 h, confirming an acute-phase response in prematurity. Studies of lung RNA showed that caeruloplasmin mRNA is expressed throughout development, with highest levels observed in adult lung. In the premature animals levels were significantly elevated 12 h after delivery, but then fell by 72 h to below those seen in normal term lung. Hyperoxia did not influence the pulmonary mRNA levels. PMID- 1627661 TI - The human glutathione S-transferases: comparison of isoenzyme expression in normal and astrocytoma brain. AB - We describe expression of alpha, mu and pi class glutathione S-transferases (GST) in brain tissue from 21 controls and uninfiltrated and tumour tissue from 17 glioma patients. GST were sequentially resolved by chromatofocusing into the GST2, GST1, GST5, GST2 (5.5), GST3, GST6 sets and the contribution of each to total activity determined. The immunological identity of these isoforms was studied using immunoblotting. The pi class GST3 isoform was the major contributor to activity in control tissue (70.9%) and, uninfiltrated (75.1%) and tumour samples (82.4%). Expression was significantly greater in the tumours (P less than 0.05). Expression of alpha isoforms GST2 and GST2 (5.5) was variable with most subjects demonstrating no detectable GST2 (B1 and B2 chromatofocused monomers). An isoform termed GST2 (5.5) chromatofocussed at pH 5.5 and cross-reacted with antisera to B1. It was detected in most control and glioma patients and comprised about 5% of total activity. The contribution of GST2 and GST2 (5.5) to activity was similar in control, uninfiltrated and tumour tissue. Two mu class enzymes, GST1 and GST5, were identified. GST1 isoforms were detected in 9 of 21 control samples, the phenotype of these and matched liver samples were identical. GST1 isoforms were detected in 4 of 16 tumour samples, a significantly lower incidence than in a previously established control group. GST5 was expressed in most samples, the contribution of this locus to activity was significantly reduced in the tumours (5.2%) compared with control samples (14.5%). PMID- 1627662 TI - Use of cytosolic metabolite patterns to estimate free magnesium in normoxic myocardium. AB - Cytosolic free magnesium (Mgf) is considered relatively constant. To test this concept, Mgf was estimated during hyperkalemic ventricular akinesis, normal and maximum adrenergic stimulation, and sulfate loading of the normoxic perfused guinea-pig heart. The Mgf estimates utilized a new sliding scale derived from the Mg(2+)-dependence of glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase (GAPDH/PGK). The pseudo constant K'GAPDH.K'PGK was measured as ([creatine phosphate][3-phosphoglycerate][lactate]KLDH)/([creatine][Pi] [glyceraldehyde 3 phosphate][pyruvate]KCK), which varied with magnesium due to KCK (CK, LDH = creatine kinase, lactate dehydrogenase). However, the correct magnesium dependencies of the true constants KGAPDH.KPGK and KCK were taken from the literature. The [Mg2+] at which pseudo K'GAPDH.K'PGK equalled true KGAPDH.KPGK was the best estimate of Mgf.Mgf fell to approximately 0.13 mM in hyperkalemic arrest from a control of approximately 0.6 mM, rising to approximately 0.85 mM only during maximum adrenergic stress. Mgf increased further to approximately 1.3 mM during sulfate loading which induced ATP catabolism. Mgf and ATP were reciprocally related. Thus; (1) myocardial free [Mg2+] judged from GADPH/PGK mass action relations changed appreciably only under extreme physiological states; (2) ATP was a major chelator of Mg2+ in perfused myocardium, i.e., acute ATP pool size reduction may be associated with increments in Mgf. PMID- 1627663 TI - Substance abuse prevention. PMID- 1627664 TI - Public policy statement on prevention. PMID- 1627665 TI - Substance abuse prevention: competence enhancement and the development of positive life options. AB - Recent advances in the field of substance abuse prevention have derived from a consideration of the etiology of substance use and have also been solidly grounded in psychological theory. Evaluation studies of psychosocial prevention interventions have become increasingly rigorous, and clearly demonstrate that there are effective approaches to prevention. The Life Skills Training Program is an example of a competence enhancement approach to substance abuse prevention. While research with this approach demonstrates its effectiveness at reducing substance use behavior, experience working with disadvantaged youth suggests the need to broaden the concept of competence enhancement. Specifically, recommendations are made for formalizing the concept of positive life options as a potentially important component of substance abuse prevention. PMID- 1627666 TI - Etiologies and consequences of adolescent drug use: implications for prevention. AB - This paper reviews recent results and work in progress from a longitudinal study of drug use etiologies and consequences. Early- and mid-adolescent drug use patterns, personality, and behavioral correlates were studied in a large sample of normal youth beginning in the mid-1970's. To determine the correlates and consequences of adolescent drug use, controlling for related tendencies such as lack of social conformity and deviant friendship networks, 654 youngsters were followed into young adulthood and their behaviors and lifestyles evaluated. Teenage drug use was found to disrupt many critical developmental tasks of adolescence and young adulthood. Tendencies to use many different drugs as an adolescent led in young adulthood to increased drug crime involvement, decreased college involvement, increased job instability, income, psychoticism, and stealing episodes. Intervention efforts should be directed not only towards decreasing drug use, but also towards improving personal maturity, social skills, and economic opportunities. PMID- 1627667 TI - An integrated model for prevention and treatment of drug abuse among American Indian youth. AB - American Indian youth have been shown to be at high risk for drug abuse. Epidemiological studies of Indian school students over the past two decades have revealed rates of use consistently higher than those found for other youth. Socioeconomic and historical factors have led to conditions that put a great deal of stress on the family and other support systems which in part account for the seriousness of the problem. A model is presented which can guide both prevention and treatment efforts addressing drug abuse in Indian communities. Five variable domains, social structure, socialization factors, psychological variables, peer associations and drug use, are related in an integrated structure. By following the progression of the etiological variables, a stepwise plan can be developed to organize interventions. Although the model has immediate utility, a number of further research questions are outlined that will enhance its application. PMID- 1627668 TI - Job satisfaction among substance abuse prevention personnel. AB - This study of military substance abuse prevention personnel examined the relationship of job satisfaction with perceived importance to unit mission and frequency of performance vis-a-vis five prevention duties. Findings indicated a positive association between job satisfaction and perceived importance for all five duties. Results suggest a conditional positive relationship between performance frequency and job satisfaction only for duties involving one-to-one interaction. Findings applicable to non-military settings and implications for further research are discussed. PMID- 1627670 TI - When to target elderly patients. Sooner is better. PMID- 1627669 TI - William James' legacy to Alcoholics Anonymous: an analysis and a critique. AB - When evolving a philosophy and a "modus operandi" the pioneers of Alcoholics Anonymous made significant use of William James' Varieties of Religious Experience. Indeed, although AA carefully picked and chose various of James' ideas which seemed particularly relevant, James' imprint is clearly stamped upon AA philosophy and methodology. Here, I will review James' work and explore what specific ideas were particularly relevant to AA's evolution as a self-help movement. The implications of this heritage will be explored. PMID- 1627671 TI - Platelets, eicosanoids and aging. PMID- 1627672 TI - Nutritional status of the very old: anthropometric and biochemical findings in apparently healthy women in old people's homes. AB - To obtain reference values for comparison with malnourished geriatric patients, the nutritional status of 50 apparently healthy women aged 75 or older living independently in two old people's homes in Heidelberg was examined. All women were able to walk, and were free from overt disease and signs of mental deterioration. Anthropometric measurements (body height and weight, triceps skinfold thickness, midarm circumference) and biochemical determinations of protein and vitamin status were performed. Anthropometric parameters were similar to those obtained in "younger" samples of healthy elderly, lower than those reported in younger adults, and markedly greater than those reported in geriatric patients. The majority of biochemical findings were within normal reference ranges established for healthy young adults. Only plasma retinol concentrations were below the reference limit in 8 women (16%). These findings show clearly that even in the very old, major alterations in biochemical indicators of nutritional status are rare. Neither advanced age nor institutionalization are associated with malnutrition. This obviously suggests that malnutrition in old age is mainly related to physical and mental disabilities. PMID- 1627673 TI - Intracranial meningiomas in patients over 70 years old. Follow-up in operated and unoperated cases. AB - Forty-six cases of intracranial meningioma in patients above 70 years of age form the basis of this study; 34 underwent surgery while 12 did not. The decision to operate was based on the general condition of the patient, evaluated according to the Karnofsky index, neurological conditions, the site and dimensions of the tumor, and the presence of peritumoral edema. The post-surgical mortality rate was 11.5% at 30 days, and 20% at 3 months. Long-term follow-up in both patient groups ranged from 1 to 5 years, and quality of life was evaluated by the Karnofsky index. Five operated patients died during follow-up (only 1 from intracranial pathology); the 22 survivors showed further improvement in their grading level compared to scores immediately following surgery. Among the unoperated patients, 6 died within two years of diagnosis, all from causes related to intracranial pathology; among the survivors, the Karnofsky index was unchanged in 2, and diminished in the other 4 cases. PMID- 1627674 TI - Aging: a challenge for psychology and psychologists. We are living in a graying world. PMID- 1627675 TI - Dementia patients with low serum cobalamin concentration: relationship to atrophic gastritis. AB - Serum concentrations of group I pepsinogens (pepsinogen-I) and gastrin were determined in patients with dementia disorders in order to assess the relationship, if any, between these indices of gastric mucosal function and serum cobalamin (vitamin B12) levels. A significant positive correlation between pepsinogen-I and B12 and, as expected, an inverse relationship between gastrin and pepsinogen-I concentrations was found, indicating that vitamin B12 deficiency was mainly determined by gastric mucosal atrophy (atrophic gastritis) in this West-Swedish sample of patients with dementia disorders. Patients with low B12 but normal gastrin and pepsinogen-I concentrations should, therefore, be further evaluated for possible nutritional deficiency, as well as nongastric causes of poor B12 assimilation from the diet. PMID- 1627676 TI - Response stability and reliability in longitudinal health evaluations. AB - Two approaches were used to study the stability over time and intravisit reliability of health questions and clinical medical examination items in the Baltimore Longitudinal Study of Aging (BLSA). The stability of responses was determined by evaluating the medical history and physical examination completed at each visit to identify items that once answered in a positive manner, should continue to be answered positively over time. Stability for each question and subject was calculated by the number of positive responses following the first positive response divided by the total number of visits following the first positive response. For 35 questions answered by the subject, the stability was 58% by a simple average or 64% when weighted for the percentage of subjects who had a positive response to the question; for 10 physician-asked questions, the corresponding figures were 29% or 36%. Eighteen items from the physical examination had a stability of 34% or 37%. Intravisit reliability was estimated by comparing responses from the general health questionnaire to responses on the Cornell Medical Index completed at the same visit. Subject-completed questions had substantial agreement (Kappa = 0.74, for questions worded the same), while physician-asked questions had moderate agreement (Kappa = 0.44). PMID- 1627677 TI - Assessing hip fracture risk in a population-based health survey: the NHANES III osteoporosis component. AB - A unique study of osteoporotic hip fracture risk, currently being conducted as part of a national health survey of the United States population, is described. The osteoporosis component of the third National Health and Nutrition Examination Survey (NHANES III) will provide data on multiple risk factors for hip fracture, including bone density of the proximal femur, from a nationally representative sample of adults that includes the very old. The minimum age for inclusion in the component is 20 years, so risk factors can be examined across the adult age range. The component includes men as well as women, and blacks and Mexican Americans as well as non-Hispanic whites. Finally, a longitudinal follow-up of the cohort will allow risk factor data to be related to subsequent hip fracture occurrence. PMID- 1627678 TI - Readmissions to a geriatric medical unit: is prevention possible? AB - Of the 622 patients admitted to a geriatric medical unit during the period November 1985 to October 1986, 211 (33.9%) had been discharged from hospital within the previous year. Of these, 117 (55.5%) had previously been admitted to the geriatric medical unit (18.8% of all admissions). The reasons for readmission were deterioration of existing disease (47.4%), new medical events (33.2%), poor management of previous discharge (9.5%), and social problems (5.7%). Age was not a significant factor influencing readmission. Readmission was judged preventable by better management of the previous admission and discharge in only 33 cases (15.6% of readmissions). A prospective study of the patients discharged in the same year revealed that 19.3% were readmitted in the following year, and of these readmissions 2.3% were considered to be preventable. There was no difference in medical causes for readmission in the two years. A significant number of the patients readmitted in both years studied was categorized as "high dependency". The figures suggest that although unplanned readmission is common, it is generally not preventable by better management of the previous admission, and often reflects a highly dependent and medically frail group of patients, in whom early intervention with readmission is appropriate. PMID- 1627679 TI - Survival prognosis in geriatric patients admitted to permanent institutional care. AB - The influence of clinical and laboratory findings on the two-year survival prognosis was investigated in 558 geriatric patients admitted to permanent institutional care. The patients surviving for two years (52%) were somewhat younger (79 vs 82 years, p less than 0.01), and on admission had significantly higher diastolic blood pressure (p less than 0.001), serum thyroxin (p less than 0.05), serum albumin (p less than 0.01) and blood haemoglobin (p less than 0.05), but lower treatment score (p less than 0.001), serum creatinine (p less than 0.001), and fasting plasma glucose (p less than 0.05). Decreased survival prognosis was also found in patients with abnormal serum sodium, chloride, and potassium (p less than 0.05 or less). However, an excess mortality of patients with abnormal laboratory data occurred within the first month after admission. Stepwise logistic regression analysis disclosed that the three-month survival prognosis was significantly impaired by low blood pressure (less than 110/70 mmHg), high treatment score (greater than 22), elevated serum creatinine (greater than 150 mumol/L), use of digitalis and atrial fibrillation. Poor two-year survival was further associated with the use of diuretics, and diabetes mellitus. The risk for death was lowest in patients with elevated blood pressure (greater than 160/95 mmHg). These data verify the significance of the clinically common diseases and indicators of homeostasis in the assessment of geriatric hospital patients, and demonstrate the nature of "terminal decline" in geriatric practice. PMID- 1627680 TI - Twenty-four hour blood pressure monitoring in the Syst-Eur trial. AB - This article describes the objectives and protocol of a study on ambulatory blood pressure in elderly patients with isolated systolic hypertension. This study constitutes an optional side-project to the Syst-Eur trial. The multicentre Syst Eur trial investigates whether antihypertensive treatment of elderly patients with isolated systolic hypertension will influence the incidence of stroke. Secondary endpoints include cardiovascular events, such as myocardial infarction. The main objective of the side-project is to investigate whether ambulatory blood pressure monitoring will improve the prediction of cardiovascular complications based on blood pressure measurement in the clinic. The side-project also provides the opportunity to evaluate the diurnal profile of blood pressure in elderly patients with isolated systolic hypertension randomized to placebo or active antihypertensive treatment. PMID- 1627681 TI - Simulation of adaptive mechanisms in the vestibulo-ocular reflex. AB - The vestibulo-ocular reflex (VOR), which stabilizes the eyes in space during head movements, can undergo adaptive modification to maintain retinal stability in response to natural or experimental challenges. A number of models and neural sites have been proposed to account for this adaptation but these do not fully explain how the nervous system can detect and correct errors in both gain and phase of the VOR. This paper presents a general error correction algorithm based on the multiplicative combination of three signals (retinal slip velocity, head position, head velocity) directly relevant to processing of the VOR. The algorithm is highly specific, requiring the combination of particular sets of signals to achieve compensation. It is robust, with essentially perfect compensation observed for all gain (0.25X - 4.0X) and phase (-180 degrees - +180 degrees) errors tested. Output of the model closely resembles behavioral data from both gain and phase adaptation experiments in a variety of species. Imposing physiological constraints (no negative activation levels or changes in the sign of unit weights) does not alter the effectiveness of the algorithm. These results suggest that the mechanisms implemented in our model correspond to those implemented in the brain of the behaving organism. Predictions concerning the nature of the adaptive process are specific enough to permit experimental verification using electrophysiological techniques. In addition, the model provides a strategy for adaptive control of any first order mechanical system. PMID- 1627682 TI - Vestibuloocular reflex arc analysis using an experimentally constrained neural network. AB - The primary function of the vestibuloocular reflex (VOR) is to maintain the stability of retinal images during head movements. This function is expressed through a complex array of dynamic and adaptive characteristics whose essential physiological basis is a disynaptic arc. We present a model of normal VOR function using a simple neural network architecture constrained by the physiological and anatomical characteristics of this disynaptic reflex arc. When tuned using a method of global optimization, this network is capable of exhibiting the broadband response characteristics observed in behavioral tests of VOR function. Examination of the internal units in the network show that this performance is achieved by rediscovering the solution to VOR processing first proposed by Skavenski and Robinson (1973). Type I units at the intermediate level of the network possess activation characteristics associated with either pure position or pure velocity. When the network is made more complex either through adding more pairs of internal units or an additional level of units, the characteristic division of unit activation properties into position and velocity types remains unchanged. Although simple in nature, the results of our simulations reinforce the validity of bottom-up approaches to modeling of neutral function. In addition, the architecture of the network is consistent with current ideas on the characteristics and site of adaptation of the reflex and should be compatible with current theories regarding learning rules for synaptic modification during VOR adaptation. PMID- 1627683 TI - Synaptic potentials and transfer functions of lamprey spinal neurons. AB - 1. Electrotonic and chemical synaptic potentials were measured as a function of frequency of presynaptic action potentials. Over the frequency range from 0.02 to 10 Hz, the electrotonic synaptic potential was constant, while the chemical synaptic potential decreased in magnitude. Above 10 Hz, both synaptic events decreased in magnitude consistent with filtering by the dendritic structures. 2. Electrotonic synaptic transfer functions from 0.5 to 100 Hz were measured for the I1 reticulospinal Muller axon to spinal neuron electrotonic synaptic junction of the lamprey spinal cord using paired recordings from the pre-synaptic terminals and the post-synaptic neurons. In addition to this two-point synaptic transfer function, individual single point impedance functions of both the post-synaptic soma and the pre-synaptic axon terminal were measured. 3. The measured functions were interpreted with a computational model based on a three dimensional reconstruction of a Lucifer yellow filled motoneuron. Simulations of the model for a synaptic location of the I1 synapse were consistent with the measured synaptic transfer functions. 4. Synaptic potentials were simulated for inputs on dendrites near the I1 axon as well as distal dendritic regions. The high frequency filtering increased as the synaptic location was moved from the soma to the periphery, but the potential response on distal dendrites was larger than would have been predicted from the end of the equivalent cylinder of a Rall model that was used to fit soma impedance functions. 5. Electrotonic post-synaptic potentials were enhanced by the activation of a TTX-sensitive negative conductance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627685 TI - Purposive behavior and cognitive mapping: a neural network model. AB - This study presents a real-time, biologically plausible neural network approach to purposive behavior and cognitive mapping. The system is composed of (a) an action system, consisting of a goal-seeking neural mechanism controlled by a motivational system; and (b) a cognitive system, involving a neural cognitive map. The goal-seeking mechanism displays exploratory behavior until either (a) the goal is found or (b) an adequate prediction of the goal is generated. The cognitive map built by the network is a topological map, i.e., it represents only the adjacency, but not distances or directions, between places. The network has recurrent and non-recurrent properties that allow the reading of the cognitive map without modifying it. Two types of predictions are introduced: fast-time and real-time predictions. Fast-time predictions are produced in advance of what occurs in real time, when the information stored in the cognitive map is used to predict the remote future. Real-time predictions are generated simultaneously with the occurrence of environmental events, when the information stored in the cognitive map is being updated. Computer simulations show that the network successfully describes latent learning and detour behavior in rats. In addition, simulations demonstrate that the network can be applied to problem-solving paradigms such as the Tower of Hanoi puzzle. PMID- 1627684 TI - Detection of motor unit action potentials with surface electrodes: influence of electrode size and spacing. AB - A model of the motor unit action potential was developed to investigate the amplitude and frequency spectrum contributions of motor units, located at various depths within muscle, to the surface detected electromyographic (EMG) signal. A dipole representation of the transmembrane current in a three-dimensional muscle volume was used to estimate detected individual muscle fiber action potentials. The effects of anisotropic muscle conductance, innervation zone location, propagation velocity, fiber length, electrode area, and electrode configuration were included in the fiber action potential model. A motor unit action potential was assumed to be the sum of the individual muscle fiber action potentials. A computational procedure, based on the notion of isopotential layers, was developed which substantially reduced the calculation time required to estimate motor unit action potentials. The simulations indicated that: 1) only those motor units with muscle fibers located within 10-12 mm of the electrodes would contribute significant signal energy to the surface EMG, 2) variation in surface area of electrodes has little effect on the detection depth of motor unit action potentials, 3) increased interelectrode spacing moderately increases detection depth, and 4) the frequency content of action potentials decreases steeply with increased electrode-motor unit territory distance. PMID- 1627686 TI - Single evoked potential reconstruction by means of wavelet transform. AB - We would like to propose a method of single evoked potential (EP) extraction free from assumptions and based on a novel approach--the wavelet representation of the signal. Wavelets were introduced by Grossman and Morlet in 1984. The method is based on the multiresolution signal decomposition. Wavelets are already used for speech recognition, geophysics investigations and fractal analysis. This method seems to be a useful improvement upon Fourier Transform analysis, since it provides simultaneous information on frequency and time localization of the signal. We would like to introduce wavelet formalism for the first time to brain signal analysis. One of the most important problems in this field is the analysis of evoked potentials. This signal has an amplitude several times smaller than EEG, therefore stimulus-synchronized averaging is commonly used. This method is based on several assumptions. Namely it is postulated that: 1) EP are characterized by a deterministic repeatable pattern, 2) EEG has purely stochastic character, 3) EEG and EP are independent. These assumptions have been challenged e.g. the variability of the EP pattern was demonstrated by John (1973) by means of factor analysis. In view of the works of Sayers et al. (1974) and Basar (1988) EP reflects the reorganization of the spontaneous activity under the influence of a stimulus and it is connected with the redistribution of EEG phases. Several attempts to overcome the limitation of the averaging method have been made. Heintze and Kunkel (1984) used an autoregressive moving average (ARMA) model to extract evoked potentials from 2 segments. This was possible under two conditions: high signal to noise ratio and clear separation of the EEG and EP spectra.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627687 TI - Information in channel-coded systems: correlated receivers. AB - Noise correlation can easily occur in the densely connected systems observed in biological information processing. We study the consequences of noise correlation for a statistically optimal processing of noise-perturbed receptor array outputs. We find a critical importance of the noise correlation length as compared to the receptors' tuning width for both the structure and the performance of the ideal observer. We show the general consistency of our scheme with psychophysical discrimination thresholds obtained in human spatial vision. PMID- 1627688 TI - Heart-lung transplantation: indications and technique. PMID- 1627689 TI - Results of lung transplantation. PMID- 1627690 TI - Pediatric lung transplantation. PMID- 1627691 TI - Retransplantation following isolated lung transplantation. AB - The results of retransplantation for early allograft failure are discouraging. Fortunately, with recent technical advances and improved postoperative immunosuppression, airway complications have been significantly reduced. It is now unusual to see patients with airway complications following lung transplantation. This group of patients is not likely to represent a large population in need of retransplantation in the future. However, rejection mediated OB remains a persistent problem seen in all transplant centers. The group of patients who deteriorate despite augmented immunosuppression will put increasing pressure on transplant programs to provide the only known solution for survival: retransplantation. In the Toronto experience, only 1 patient survived early retransplantation. Three of the 5 recipients retransplanted late in their course have survived and 2 are presently alive and well. Yet this is in sharp contrast to the current 80% 1-year survival for initial transplant recipients. As the demand for donor lungs increases with the growing need for first-time procedures, the use of donor lungs for retransplantation becomes a significant problem. The decision whether to allocate a donor lung (and commit significant hospital resources) to a retransplant recipient or to a first-time recipient is difficult. A patient with early graft failure has a dismal prognosis and a decision not to retransplant may be straightforward. However, the decision to retransplant a patient who has developed OB late following their initial transplant is much more difficult. It is still our responsibility to manage this limited resource and provide donor lungs to those who have the optimal chance of survival. PMID- 1627692 TI - Diagnosis and management of acute and chronic lung rejection. PMID- 1627694 TI - Airway complications after lung transplantation. PMID- 1627693 TI - Complications following lung transplantation. PMID- 1627695 TI - Lung transplantation. PMID- 1627696 TI - Lung transplantation: recipient selection. PMID- 1627697 TI - Lung transplantation: donor selection. PMID- 1627698 TI - Lung preservation. AB - Pulmonary transplantation is now a clinical reality that offers hope to large numbers of patients with end-stage lung disease. Current methods of preserving pulmonary function allow for transplantation, but operation must be expeditious, and transportation time and operating time become critical factors in determining outcome. The ability to preserve lungs for longer time intervals could potentially allow for more widespread distribution of donor organs of unusual size or blood type, and could set the stage for more appropriate HLA matching between donor and recipient. Furthermore, a more thorough understanding of the pathophysiology of preservation injury will likely lead to a better understanding of the pathophysiology of other types of lung injury. In turn, this could increase the size of the pulmonary donor pool by allowing transplantation of lungs with suboptimal gas exchange function at the time of donor brain death. Finally, a more thorough understanding of lung metabolism and determinants of cellular viability in the lung would be useful for the potential application of the use of lungs from circulation-arrested cadavers for transplantation. PMID- 1627699 TI - Single lung transplant: indications and technique. PMID- 1627700 TI - Bilateral lung transplant: indications and technique. PMID- 1627702 TI - Ethics of health research. PMID- 1627701 TI - Medical care for institutionalised elderly people in Singapore. AB - This study examined physical and financial arrangements for medical care of institutionalised elderly people in Singapore. Chief administrators of all long term care facilities were interviewed on the existing arrangements for medical care of their residents. Results showed that 66 out of a total of 68 (97%) homes arranged medical care for residents. Of those, 29 homes offered on-site medical care with alternative arrangements when the in-house facilities were not operating. While government-owned homes would pay for all medical costs incurred by their residents, over 48% of voluntary homes and 87% of commercial homes required residents to be financially responsible for their care. The availability of financial support given to residents for payment of medical care was found to be associated with the type of sponsorship of the homes. While there was adequate physical access to medical care, the lack of financial support would pose a potential barrier to use of medical care for institutionalised elderly people. PMID- 1627703 TI - Alcohol advertising. PMID- 1627704 TI - Low birthweight and socioeconomic status, Victoria 1982 to 1986. AB - The aim of this study was to evaluate the association between the incidence of low birthweight and socioeconomic status, in particular whether the relationship was different for very low birthweight (less than 1500 g) and moderately low birthweight (1500 to 2499 g). The study population was births from 1982 to 1986 to women resident in Victoria (300,704). Data on socioeconomic status were derived from an indicator developed by the Australian Bureau of Statistics from the 1981 census and applied to postcodes. Using the rates of very low birthweight and moderately low birthweight in the highest socioeconomic status decile as the reference value we found that the relative risk for very low birthweight was significantly raised in only the lowest socioeconomic status decile (relative risk = 1.29, 95% confidence interval (CI) 1.17 to 1.42). The relative risk for moderately low birthweight was increased in the two lowest deciles: 1.19 (CI 1.12 to 1.26) and 1.09 (CI 1.01 to 1.17) respectively. Women not married at the time of the birth had a higher rate of low birthweight and were more likely to live in the lower socioeconomic status postcode areas. The relationships between very low birthweight, moderately low birthweight and socioeconomic status were attenuated but still significant when this factor was taken into account. Differences in low birthweight by socioeconomic status decile were not apparent for nonsmoking women. The relationship between smoking and low birthweight was different in the two lowest socioeconomic status deciles: the relative risk of low birthweight in smokers was 2.60 (CI 1.73 to 3.91) compared with a relative risk of 1.64 (CI 1.33 to 2.03) in deciles 3 to 10. PMID- 1627705 TI - A family study of coronary risk factors in Geelong. AB - A study of coronary risk factor relationships was carried out in 213 families with adolescents in Geelong, Victoria, Australia, in 1987. Weight, height, skinfold thicknesses, body circumferences, blood pressure and serum cholesterol were measured in both parents and children and other relevant information was obtained by questionnaire. The study group did not differ significantly from the Geelong population with respect to the proportion of Australian-born parents but contained a significantly higher proportion than expected of fathers who had a university degree or diploma. Twenty-five per cent of adolescents, 30% of mothers and 38% of fathers were positive for at least one of the three major established coronary risk factors. Significant correlations between parents and children, but not between parents, were found for total cholesterol and systolic blood pressure, while significant correlations were observed both between parents and children and between parents for measures of body size, body fatness and body fat distribution. The strongest predictors of risk factor status in adolescence were both parents with total cholesterol at or above 5.5 mmol/l, one or more parents who smoked and one or more grandparents with a history of coronary heart disease. Body mass index in adolescence was unrelated to heart disease risk factor status in adolescence or to a family history of heart disease. During early childhood and adolescence, parental risk factor status, rather than anthropometric or risk factor screening of the children themselves, is likely to provide the best guide to those at risk for an adverse coronary risk factor profile. PMID- 1627707 TI - Ecological disruption and human health: the next great challenge to public health. PMID- 1627706 TI - Ear health of aboriginal primary school children in the Eastern Goldfields Region of Western Australia. AB - The ear health and state of hearing of 642 Aboriginal children living in the Eastern Goldfields of Western Australia in 1989 was assessed by audiometry, otoscopy and tympanometry in order to establish the efficacy of the existing ear health program. A heavy burden of ear disease and hearing loss is reported and the findings are compared with previous surveys. A conclusion is drawn that the ear health of this population has not improved in the last decade. PMID- 1627708 TI - Measles immunisation compliance: poor impact of bicentennial measles control campaigns on children under five. AB - A measles immunisation survey was conducted among children who enrolled in school kindergarten classes in the Eastern Sydney Area in 1989. Its aims were to determine baseline compliance rates, to identify subpopulations at risk of poor compliance and to evaluate the impact of the bicentennial measles control campaigns on compliance among children under five years. All 73 schools participated, questionnaires were returned by 2230 (81.4%) children, and compliance with immunisation was 91.3%. 89.1% of children attending public schools were immunised, compared to 91.9% of Catholic school pupils and 95.8% of independent school pupils (chi 2 = 21.4, P less than 0.001). Among public school children, 91.6% of pupils from English-speaking families were immunised in comparison to 81.4% of pupils from non-English-speaking backgrounds (chi 2 = 20.5, P less than or equal to 0.001). The fraction of previously unimmunised children who were known to have been immunised during each year of the measles control campaigns was 16% in 1986-87, 10% in 1987-88 and 9% in 1988-89. These small increments in immunisation uptake suggest that under-five-year-olds were not effectively targeted by the measles control campaigns. However, no control group was evaluated. Immunisation delivery systems must be designed which ensure that all children receive measles-mumps-rubella vaccine as soon as possible after the first birthday. Immunisation promotions and service providers will need to target specific language and socioeconomic groups. PMID- 1627709 TI - Aspirin use in children: heeding the warning? AB - In 1986, the Australian Government issued warnings about the use of aspirin for children and adolescents after the link had been established between aspirin use and Reye's syndrome in America. This study questioned a representative community sample of parents in Newcastle, New South Wales, about their awareness of this caution, and their recent aspirin use for children under 18 years. While 65% of women and 47% of men reported that they were aware of the Government recommendations, only 8% of women and 9% of men reported obtaining this information from the printed warning on the medicine container or packet. Despite awareness of the warnings, almost one third of parents reported administering aspirin to their children. When it is necessary to caution patients about the use of over-the-counter medications, it is not sufficient to use package labelling as the main site of information. PMID- 1627710 TI - The public perception of the risks and benefits of alcohol consumption. AB - A survey of the community was undertaken in August 1989 to assess the public's perception of the risks and benefits of alcohol use, and their understanding of recommended levels of safe alcohol consumption. A household sample of 500 men and women (18 to 65 years) in metropolitan and rural New South Wales were asked their opinions about the risks and benefits of alcohol use, the health and social consequences of 'drinking too much', and the number of standard drinks that would produce a low, medium and high risk to the health of an adult man and woman. The major perceived benefits of alcohol use were relaxation and medication; the major health and social problems attributed to alcohol abuse were brain and liver damage, and domestic violence and family problems. The quantities of alcohol which respondents thought could be consumed with a 'low' risk to health were close to National Health and Medical Research Council recommended levels of safe consumption. PMID- 1627711 TI - Prevalences and perceptions of licit and illicit drugs among New South Wales secondary school students, 1989. AB - This paper presents findings on drug prevalences for licit and illicit drugs among New South Wales secondary school students (n = 3753) in late 1989. It also considers the accuracy of students' perceptions of the drug causing the most and fewest drug-related deaths. Data were analysed by age and gender, using logistic regression for the prevalence data. Findings indicate that licit drugs (tobacco, alcohol and analgesics) were the most frequently and widely used. Rates for illicit drugs were low, although there was some degree of experimental use of cannabis which increased amongst older males. Perceptions were found to be inaccurate in emphasising the dangers of the illicit drug heroin over those of the licit drugs tobacco and alcohol. Reasons for these findings are discussed, and more in-depth research recommended into the relationship between drug prevalences and perceptions for different age groups, and its relevance for planning drug prevention initiatives. PMID- 1627712 TI - Changes in reported drug prevalence among New South Wales secondary school students, 1983 to 1989. AB - Three drug use surveys employing a standardised questionnaire format and sampling procedure were conducted on samples of New South Wales school students in 1983, 1986 and 1989. Alcohol and tobacco were the most frequently used substances across the surveys, with rates of use of illicit substances being considerably lower. Declines in the prevalence of alcohol, tobacco and stimulant use were found between 1983 and 1986 and between 1986 and 1989 for both males and females. Rates of use of inhalants, sedatives, hallucinogens and narcotics declined between 1983 and 1986, but remained unchanged between the 1986 and 1989 samples. Cannabis use declined significantly among females between 1983 and 1989, but not among males. Possible reasons for the general decline in drug use over the six year period are discussed. PMID- 1627713 TI - The impact of a screening mammography program on Sydney general practitioners. AB - The aim of this study was to determine changes in Sydney general practitioners' (GPs) knowledge about, attitude towards and intention to recommend screening mammography over the two years since a screening mammography program was first implemented in the Central Sydney Health Service (CSHS) area. 123 GPs from the CSHS area were selected from a list maintained by the Breast X-ray Programme, while 127 GPs from the rest of Sydney were selected from the Yellow Pages telephone directory. The overall response rate was 84 per cent. Outcomes were assessed by a self-administered questionnaire covering knowledge, attitudes and beliefs, self-report of recent referral practice, intention to recommend, and sources of information about mammography screening. Demographic data were also collected. Results showed that overall knowledge has increased both inside and outside the CSHS area, but important deficiencies in knowledge remain in both areas. Attitudes to screening mammography have improved in the CSHS area, especially regarding the efficacy of screening mammography and patient compliance. Importantly, positive views of screening mammography have declined outside the CSHS area, especially about whether screening mammography can save women's lives. GPs in both areas remain concerned about costs. The presence and strategies of the Breast X-ray Programme have had some positive effect on the attitudes of GPs towards, but not knowledge of, screening mammography. PMID- 1627714 TI - Valuable health: what do we want, and how do we get it? PMID- 1627715 TI - Evaluating the impact of a promotional campaign for screening mammography: who attends? AB - The Breast X-ray Programme of the Central Sydney Health Service is one of 11 pilot programs in Australia assessing the best methods of delivering population based mammographic screening. The aim of this study was to determine the attendance rate and to describe sociodemographic predictors of attendance in an area serviced by the program. A well-defined population of approximately 4500 women aged 45 to 70 was identified within the Central Sydney area for intensive testing of recruitment strategies. After four visits (spanning two years) to the area by a mobile screening van, 48% of the women were screened. Women from non English-speaking backgrounds were just as likely to attend as women from English speaking backgrounds, probably because special attention was given to recruiting these women. Older women from English-speaking backgrounds were less likely to attend, whereas no age trend existed for women of non-English-speaking backgrounds. Sampled attendance data of women from English-speaking backgrounds showed that women with more education were more likely to attend screening. Women who were employed were just as likely to attend as those who were not. In order to screen 70% of the targeted population as set forth for a national mammography screening program, it appears that community recruitment efforts alone will not be sufficient. With special attention to recruitment coverage, older women and women from non-English-speaking backgrounds can be successfully recruited. Special attention will also need to be focused on encouraging attendance in women who have less formal education. PMID- 1627716 TI - Evaluating the impact of a promotional campaign for screening mammography: women's knowledge and sources of awareness. AB - The Breast X-Ray Programme of the Central Sydney Health Service was advertised by generalised strategies aimed at the total community, including poster and pamphlet distribution, and strategies aimed at general practitioners, supplemented by written invitations and recommendation from the general practitioner, invitations for friends, and invitations from the service using the electoral listing. In order to evaluate the reach or impact of the promotional campaign in the Drummoyne local government area, telephone interviews were conducted with women aged 45 to 70 randomly selected from the community. Women's knowledge about breast cancer, screening and the Breast X-Ray Programme, plus sociodemographic characteristics, were obtained before screening (n = 628), 10 months (n = 93) and 2 years after screening started (n = 206). While knowledge about risk did not change, significant increases were found in the proportion of women who had heard of mammography, screening mammography specifically and the screening van. In addition there were significant increases in the proportion of women exposed to information about screening mammograms. The campaign generally had an equal effect on different sociodemographic but managed to achieve greater effects in women of non-English-speaking backgrounds and lower occupational status. A random sample of program attenders aged 45 to 70 (n = 763) were asked how they found out about the van. 'Seeing the van' was the most consistently reported source of awareness. Others included 'GPs' 'newspapers', 'other print media' and 'personal networks'. Women with additional qualifications since leaving school were more likely to state 'newspaper' and 'other print media' as a source. PMID- 1627717 TI - Ineffective recruitment strategies for screening mammography: letterbox drops and invitations for friends. AB - To test the effectiveness of two interventions to encourage women to attend for mammographic screening, four randomised trials of letterbox drops were conducted. Leaflets about the screening service (n = 3984) were distributed to households within defined areas. Attendance from the 79 streets where a drop was made was compared with attendance from 78 control streets before and after the drop. No major effects were found either within each trial or across trials. In the second intervention, 69 women who attended the service were offered invitations for two friends. An additional 21 attenders were approached with the offer of an incentive to recruit friends. Invitations included an explanatory letter with an appointment time, a pamphlet and a contact phone number. The final response rate was only 7% and an incentive of an instant scratch lottery ticket for the original attender did not improve the response. Thus we identified two interventions with no major effect in recruiting women to mammographic screening. PMID- 1627718 TI - Preferences of rural Victorian women for screening mammography services. AB - The aim of this study was to examine rural women's access to regional fixed-site screening mammography services and their preferences for either a mobile service or a fixed-site centre. One hundred and thirty-seven women aged 49 to 69 from rural Victoria were interviewed in June 1991. Eighty-five per cent of women normally go to major towns which are possible screening sites at least once every six months, spending an average of five hours each visit. Around 77% of women said they would be likely to go to a fixed site while 86% said they would be likely to go to a mobile service. If the fixed-site centre was at a major town not usually frequented, this would be a deterrent to 58% of women. A decision to widely implement mobile screening in rural areas of Victoria is not justified at this time, but pilot mobile services should be considered. PMID- 1627719 TI - Trends in general practitioner distribution from 1984 to 1989. AB - An analysis of the distribution of general practitioners by electorates during the six years 1984 to 1989 showed that the maldistribution of practitioners in Australia has worsened despite significant increases (26%) in total general practitioner numbers. One in five rural electorates had worse population-to general-practitioner ratios in 1989 than in 1984. The changes in distribution of general practitioners ran counter to the changes in distribution of the population over the period studied. In 1984, the 38.7% of the population living in rural Australia was served by 33% of the nation's general practitioners. By 1989, more of the population (39.8%) lived in rural areas but they were served by a smaller proportion (32%) of the general practitioner workforce. It is clear that many urban electorates have fewer people per general practitioner than the most generous ideal ratios, while most rural electorates have more people per general practitioner than the least generous. PMID- 1627720 TI - Progress in assessing the quality of Australian nursing home care. AB - This paper critically examines the clarity, practicality, desirability and validity of the 31 outcome standards that the Commonwealth Government introduced to assess quality of care in Australian nursing homes. Key features of the Australian system in an international context are its focus on outcomes, the limited number of standards used, and the comparatively subjective nature of some standards. Directors of nursing from 410 nursing homes in the Brisbane, Sydney, Melbourne and Adelaide metropolitan areas were interviewed as part of the Nursing Home Regulation in Action Project. The overwhelming majority reported the standards as clear and desirable. In the minority of cases where problems were raised, practicability was the basis for concern. A factor analysis of the ratings given by standards monitoring teams to these 410 homes failed to demonstrate redundancy across standards or grouping of standards by objectives. Nevertheless, the standards were sufficiently highly interrelated to justify summing to produce an overall compliance score. This study shows that the 31 standards hold up well under scrutiny, both from the perspectives of key actors in the monitoring process, and from a psychometric point of view. PMID- 1627721 TI - A five-year study of residents of a special hostel for people with dementia. AB - In order to consider whether admission to a special hostel was a desirable policy in view of the likelihood of subsequent transfer to a nursing home, this study compared the time spent by residents in a special hostel with the period in a nursing home after they were transferred out of the hostel. We also estimated the number of nursing home places necessary for residents who were transferred and studied the reasons for transfer. The setting was a special hostel in Perth, Western Australia, for 36 people with moderate or severe dementia. The periods spent in the hostel or a nursing home were calculated for all residents admitted between 1985 and 1990. Forty-two of the 84 residents admitted during the study period were transferred to nursing homes. About two thirds of the total time in the two institutions was spent in the hostel. The two principal reasons necessitating transfer to a nursing home were advancing dementia and the addition of a physical impairment. Because a major proportion of the care of selected people with dementia (who can no longer remain at home) can be undertaken in a special hostel, this facility should be included with standard hostel and nursing home in arrangements for institutional care. Between 20 and 25 nursing home places are necessary for residents transferred from a hostel of this size. PMID- 1627722 TI - Characterization of two phospholipases A2 in serum of patients with sepsis and acute pancreatitis. AB - Pancreatic phospholipase A2 and non-pancreatic ascitic phospholipases A2 were studied in sera of healthy individuals and of patients suffering from sepsis or acute pancreatitis. In gel filtration experiments, immunoreactive ascitic phospholipase A2, as determined in serum by a time-resolved fluoroimmunoassay, eluted either unassociated with an apparent M(r) of 10,000-14,000 or associated with proteins of high molecular mass. Catalytically active ascitic phospholipase A2 was associated with high molecular weight proteins. In acute pancreatitis the catalytically active and immunoreactive pancreatic phospholipase A2 eluted mainly as a protein of M(r) of 14,000. The results of the gel filtration experiments indicate that pancreatic phospholipase A2 is not associated with other proteins in human serum, whereas ascitic phospholipase A2 is associated with protein(s) of relative high molecular weight, or exists in different polymeric forms. We also purified phospholipase A2 from sera of healthy individuals by ion exchange chromatography and HPLC. The enzyme was homogenous, displayed an M(r) of approximately 13,500 as judged by SDS-polyacrylamide gel electrophoresis, and reacted with an antibody raised against ascitic phospholipase A2. PMID- 1627723 TI - Age-related changes in cerebrospinal fluid gamma-aminobutyric acid concentration. AB - The purpose of this study was to clarify the effect of aging on brain gamma aminobutyric acid metabolism. We measured the cerebrospinal fluid gamma aminobutyric acid concentration in subjects of various ages, including healthy volunteers and patients without neurological or psychiatric disease. The cerebrospinal fluid gamma-aminobutyric acid concentration was determined by radiolabelled receptor assay using [3H]gamma-aminobutyric acid. Cerebrospinal fluid gamma-aminobutyric acid was significantly higher in the control group (20s and 30s) than in the groups of subjects in their 50s, 60s, 70s and 80s. There was a significant negative correlation between cerebrospinal gamma-aminobutyric acid concentration and age (p less than 0.01). These data suggest that dysfunction of brain gamma-aminobutyric acid metabolism increases with age, and that the various symptoms caused by abnormal gamma-aminobutyric acid metabolism in the brain are therefore more likely to appear in elderly people. PMID- 1627724 TI - The extent of diffuse intravascular coagulation and fibrinolysis in patients with liver cirrhosis. AB - Twenty-five patients with different stages of liver cirrhosis were evaluated with regard to the degree of liver synthesis reduction, the extent of the decrease of blood coagulation factors and/or alterations of the fibrinolytic system. For the assessment of the residual level of liver synthesis we used pseudo-cholinesterase and serum albumin as references. We did not find a correlation between these quantities and antithrombin III or fibrinogen, but highly significant inverse correlations with tissue plasminogen activator activity and D-dimer concentration. We found considerable alterations in the concentrations of the coagulation and fibrinolysis factors, with the exception of fibrinogen and plasminogen activator inhibitor. Significant increases were seen for thrombin antithrombin III complex, tissue plasminogen activator activity and D-dimer, while significant decreases were seen for antithrombin III and alpha 2 antiplasmin, compared with a group of healthy volunteers. In the group of patients with liver cirrhosis and reduced liver synthesis, as documented by lowered pseudo-cholinesterase and serum albumin, the reduction of both antithrombin III and alpha 2-antiplasmin was most prominent. Intravascular coagulation was negligibly small. For the fibrinolytic system, the increase of tissue plasminogen activator, the decrease of the fibrinolysis inhibitor (alpha 2 antiplasmin) and the elevated D-dimer concentration seem to be important. These results suggest an acceleration of fibrinolysis and the prolonged presence of cross-linked fibrin degradation products. PMID- 1627725 TI - Comparison of four procedures for measuring elastase production by Pseudomonas aeruginosa strains from cystic fibrosis patients. AB - Forty-five Pseudomonas aeruginosa strains were isolated from the sputa of cystic fibrosis patients. The elastase production of each strain was assayed in the culture supernatant using four different procedures, i.e. two immunological assays (RIA and ELISA), and two enzymatic assays, the latter employing either elastin or tetraalanine as substrate, with conductometric measurement of substrate hydrolysis. Elastase concentrations were determined from standard curves prepared with the same purified elastase, and expressed in mg of elastase per litre of supernatant. The resulting values were in the range reported in the literature, and differed greatly from one strain to another (0-230 mg/l). Linear relationships were found when assays were compared in pairs. Significant correlation coefficients were obtained (r greater than 0.76, p less than 0.001) but the values were quite different for different assays. Thus, ELISA measurements were always from three to five times higher, and RIA results were from two to five times lower, than those from the other assays. Enzymatic assays with elastin gave higher values than those using tetraalanine. Most P. aeruginosa strains produce two other proteinases, alkaline proteinase and Las A protein. Both enzymes have limited elastolytic and peptidasic activities. The presence of alkaline proteinase does not result in falsely elevated elastase values, but an increase of elastase activity was observed when Las A was preincubated with elastin. Since this increase was not observed when tetraalanine was used as the substrate, the presence of Las A in the supernatants could explain the differences observed between the enzymatic assays. The assay with the synthetic substrate is therefore preferred. PMID- 1627726 TI - Evaluation of interlaboratory proficiency surveys of bilirubin determinations in sera of newborns. AB - We evaluated the results of two surveys of neonatal bilirubin determinations in 66 Slovakian clinical chemistry laboratories. Identical control samples prepared as described by Vink (Clin. Chem. 33 (1987) 1817-1821) and commercially available control serum were used for both surveys. These control samples were analysed in the participating laboratories using various modifications of diazo techniques based on the Grof-Jendrassik principle, and direct two-wavelength spectrophotometry according to Vink (Clin. Chem. 34 (1988) 67-70). The interlaboratory precision and accuracy of these two different analytical principles were compared. For diazo techniques the CVs varied from +/- 6.8% to +/ 10.3%, while the CVs for direct spectrophotometry were between +/- 5.3% and +/- 6.4%. Better results were obtained by recalculating the raw data of the analyses from all laboratories, using the reported results for the analysis of an identical calibrant. Accuracy was evaluated as the percentage of acceptable results (within +/- 7% of the reference values). About 60% of the results obtained with diazo methods were considered acceptable, compared with about 22% of those obtained by direct spectrophotometry. However, results recalculated on the basis of the identical calibrant showed greater accuracy; acceptable results then varied between 74% and 82% of the total for the diazo techniques and from 83% to 91% for direct spectrophotometry. PMID- 1627727 TI - An indirect ELISA for urinary gonadotropins using immobilized human menopausal gonadotropin. AB - An indirect ELISA for the estimation of urinary gonadotropins is described. Human menopausal gonadotropin is adsorbed on a microtitre plate, where it serves as an immunosorbent. The residual antigonadotropin antibody is captured by the immunosorbent after reaction with the sample or standard and detected with enzyme labelled antispecies antibody (antirabbit gamma-globulin-horse radish peroxidase). The assay developed here is rapid and satisfies usual validatory criteria expected from an immunoassay. Moreover, it obviates the need for extraction of samples with acetone, as shown by the close agreement between the respective lutropin or follitropin concentrations in extracted and unextracted urine samples. PMID- 1627728 TI - A time-resolved fluoroimmuno assay of the IgM-rheumatoid factor. AB - A time-resolved fluoroimmuno assay of the IgM-rheumatoid factor is described. Aggregated rabbit IgG was coated to microtitre plates to serve as the target protein. F(ab')2-fragments from antibodies, raised in rabbits against human IgM, were labelled with Eu3+ and used in the assay to mark the bound IgM-rheumatoid factor. The labelling procedure is easy to perform, and there is no need for special equipment. The shelf life of the label at -20 degrees C is at least one year. The lower detection limit of the assay is 1.3 x 10(3) IU/l. The range over which the IgM-rheumatoid factor can be measured at a within-run precision of less than 5% without varying the dilution (working range) is 5-1200 x 10(3) IU/l. Linearity in serum dilutions is good. There is good correlation with existing methods for the assay of IgM-rheumatoid factor. This correlation is better with an assay using rabbit IgG as the target than with one using human IgG. Comparison of methods shows that standardization, despite the use of the WHO Reference Preparation as the first calibrator, remains problematic. The 95th percentile in normal bloodbank donors is 8 x 10(3) IU/l. The costs for the reagents were about 0.5 Dutch florin (ca 0.30 US-$) per well. In conclusion, the method described here is analytically at least comparable with other methods, in precision, linearity, working range etc. Finally, it is easy to perform. PMID- 1627729 TI - Automated latex nephelometric immunoassay of theophylline in human serum. AB - A latex test was adapted for the nephelometric quantitation of theophylline in human serum. The assay is fully automated on the Behring Nephelometer Analyser with a sampling rate of 150 samples per hour. There is no interference from bilirubin (up to 340 mumol/l), haemoglobin (up to 7000 mg/l), Intralipid (up to 5 g/l), or rheumatoid factor (up to 1100 x 10(3) IU/l). The theophylline standard curve extends from 1.25 to 40 mg/l. The coefficient of variation ranged from 2.4 to 7.4%. The correlation coefficient between the latex immunoassay and the TDx theophylline procedure was 0.988, calculated from the assay of 74 samples. PMID- 1627730 TI - Proposed quality specifications for the imprecision and inaccuracy of analytical systems for clinical chemistry. AB - A Working Group of the European Group for the Evaluation of Reagents and Analytical Systems in Laboratory Medicine proposes, after detailed study of the advantages and disadvantages of available strategies, the following quality specifications for analytical systems for clinical chemistry. Total imprecision should be: (a) less than one-half of the average within-subject biological variation, or (b) less than the state of the art achieved by the best 0.20 fractile of laboratories, whichever is the less stringent. The second approach may be used when data on biological variation do not exist. Inaccuracy should be: (a) less than one-quarter of the group (within- plus between-subject) biological variation, or (b) less than one-sixteenth of the reference interval, when data on group biological variation do not exist, or (c) less than twice the ideal imprecision, if the above specifications are too demanding. PMID- 1627731 TI - Symbiotic interactions in the EVOLVE III ecosystem model. AB - Parasitic feeding mechanisms were introduced into the EVOLVE III ecosystem model. The modified system exhibited a number of interesting behaviors, including obligative and facultative parasitism, transient facultative mutualism and nonsymbiotic feeding. Speciation and massive die-offs were also observed. The introduction of a symbiotic capability altered the co-evolutionary development of traits that exhibited an arms race when the symbiotic capability was not present. Stable mutualisms were not possible in the present version of the model due to the restriction that organisms were not allowed to feed both on other organisms and from the environment at the same time. The ecosystem biomass increased with increased symbiotic activity. Biomass was influenced by the balance of virulence and resistance traits in the population and decreased as these traits became more disparate. PMID- 1627732 TI - Formation of a regular dissipative structure: a bifurcation and non-linear analysis. AB - A non-linear reaction diffusion model of a negative feedback epigenetic control system is presented. The model involves synthesis of the mitotic inducing and inhibiting proteins, simultaneously with intercellular self-diffusion and cross diffusion of the latter only. The importance of negative cross-diffusion for creating a regular dissipative structure is shown. A bifurcation analysis of the non-linear diffusive system has been performed and it is concluded that bifurcation is supercritical. Lastly, using Liapunov's direct method, it is shown that the pattern evolved by the system is globally asymptotically stable. PMID- 1627733 TI - Propagation of force and the induced bending displacement along eukaryotic flagellar axoneme. AB - The mechanical forces responsible for inducing the bending movement of eukaryotic flagellar axonemes have components that propagate at velocities different from those for the displacement of the medium. These forces are subject to the Third Law of Mechanics which states the null-conservation of acting and reacting forces. Experimental demonstration of the propagating internal tensile force along the axoneme, when not accompanied by simultaneous bending displacement, demonstrates that the active force for the bending of the flagellar axoneme is part of the process of counterbalancing the corresponding reactive force to the ATP hydrolysis underlying the force generation. PMID- 1627734 TI - Bone marrow regeneration under cytotoxic drug regimens: behaviour ranging from homeostasis to unpredictability in a model for hemopoietic differentiation. AB - In the process of hemopoiesis, bone marrow stem cells differentiate into the various types of mature blood cells. We present a model for bone marrow dynamics, which retrieves its ability to continuously modulate the balance between self renewal and differentiation, even under periodic cytodestructive perturbations. Yet, a temporally stochastic perturbation results in chaotic-like behaviour which has no deterministic source. PMID- 1627735 TI - Somatic kinetics or paroral membrane: which came first in ciliate evolution? AB - The ciliate species which lack a distinctive oral ciliature are considered to represent an ancestral state in ciliate evolution. Consequently, the somatic kineties composed of kinetids (kinetosomes plus cilia and associated fibrillar systems) are thought to be the ancestral ciliature. Results on stomatogenesis in 'gymnostomial ciliates' have shown that these ciliates probably have evolved from ancestors already equipped with an oral ciliature. Thus instead of the somatic, the oral ciliature may be regarded an ancestral. Based on these ideas a hypothesis on the evolution of the ciliate kinetome (assembly of all kinetids covering the body of a given ciliate) is presented. The first step in the evolution of the kinetome was the formation of a paroral membrane, a compound ciliary organelle lying along the right side of the oral area which historically but falsely is termed membrane. It was composed of kinetosomal dyads (dikinetids), derived from the kinetid of a dinoflagellate-like ancestor. From the beginning the paroral membrane was responsible for locomotion, ingestion and for the formation of a cytopharyngeal tube which the first ciliate probably had inherited from its flagellate ancestor. In the second step a first somatic kinety was formed from the right row of kinetosomes of the paroral membrane as a result of a longitudinal splitting of the paroral membrane and a subsequent migration of the forming kinety to the right into the somatic cortex. To increase the number of somatic kineties this process was repeated until the kinety produced first reached the left border of the oral area. By this step the locomotive and the nutritional functions were differentiated between somatic and oral structures. In a third step the adoral organelles were formed from somatic kinetids left of the oral area. The primitive type of stomatogenesis was a buccokinetal one derived from the mode the flagellate ancestor used to distribute its replicated kinetosomes to the offspring cells (buccokinetal means that at least parts of the oral anlage for the posterior offspring cell has its origin in the parental oral apparatus). This hypothesis, based on comparative studies on ciliate morphogenesis, is corroborated by molecular data from other laboratories. PMID- 1627736 TI - Effects of stress on adrenal steroidogenesis blockade by aminoglutethimide. AB - After one week of AG-treatment, the adrenal cortex reveals a marked storage of lipids and cholesterol, as well as a decrease in haematic corticosterone and progesterone levels. On the contrary, when AG-treatment is associated with stress, an increase in plasma corticosterone and progesterone levels occurs, together with a less evident lipidic storage in the adrenal cortex. These results seem to indicate the possibility that, during stress, hypothalamo-hypophysis axis activation is able to remove, at least partially, the adrenal biosynthesis blockade operated by AG-administration. PMID- 1627737 TI - Measurement of carbon clearance in mice as toxicity parameter for liposomal preparations. AB - The measurement of carbon clearance in female BDF1 mice was used for the characterization of affinity of empty multilamellar (MLV) or small unilamellar vesicles (SUV) made from HEPC:CH:DCP 1:1:0,25 to the reticuloendothelial system (RES). Five mice each were treated i.v. with the corresponding liposomes or physiologic saline. At different times after treatment india ink was administered i.v. and its elimination over 15 minutes was determined by measuring the extinction in blood at 650 nm. MLV had a significant influence on the phagocytic function of RES, leading to a three-fold prolongation of elimination half time after 8h. At 48 hours the normal function of RES was restored. This effect was already seen with a dose of 0.05 ml MLV/mouse corresponding to 1.06 mg lipid. On the contrary, SUV caused no change of carbon clearance up to a dose of 0.8 ml/mouse. From these results we conclude that liposomes, especially MLV, can lead to a measurable but reversible impairment of RES function, while SUV are better suited for a by-pass of this tissue and a probable reaching of other targets, as, for example tumors. PMID- 1627738 TI - Effect of pine seed shell extract on microbial and viral infection. AB - Pretreatment of mice with ammonia extract of seed shell of Pinus Koraicenis, via the intraperitoneal or intravenous route, effectively protected them from lethal infection of Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus. The pine seed shell extract also moderately inhibited syncytium formation and cytopathogenic effect induced by human immunodeficiency virus (HIV) infection in cultured human lymphotropic virus type I (HTLV-1) positive MT-4 cells. These data suggest a medicinal potential of pine seed shell extract against opportunistic infection in HIV patients. PMID- 1627739 TI - Modulation by the insecticides heptachlor and chlordane of the cell-mediated immune proliferative responses of rhesus monkeys. AB - Peripheral blood mononuclear cells (PBMC) were isolated from heparinized blood samples from twelve young, healthy male rhesus monkeys. Triplicate cultures were made in RPMI 1640 with 10% heat-inactivated homologous plasma with or without the test mitogens (phytohemagglutinin, concanavalin A and pokeweed mitogen). Under a defined assay condition, although a different monkey responded to a different degree (3 to 4-fold difference in stimulation index) to a specific mitogen, the proliferative responses of all monkeys were affected significantly by the addition of the chlorinated hydrocarbon heptachlor or chlordane to the test cultures. The insecticides, at 10-40 microM, may also act as mitogens for the unstimulated monkey PBMC or stimulate the release of IL-2 from a mitogen stimulated culture. At 80 microM, both heptachlor and chlordane completely suppressed the proliferation and IL-2 release of the monkey lymphocytes. These studies suggest immunomodulatory effects of the insecticides heptachlor and chlordane. PMID- 1627740 TI - Ascorbic acid with cupric ions as a chemotherapy for human lung tumor xenografts implanted beneath the renal capsule of immunocompetent mice. AB - The growth of human lung carcinoma xenografts implanted beneath the renal capsule of immunocompetent mice was investigated (the six-day subrenal capsule assay) by using combinations of ascorbic acid and cupric ions. A maximum suppression of growth of this human lung tumor, LX-1, was observed at an estimated consumption level by the mice of 6 to 8 g ascorbic acid and 2 to 5 mg cupric ions per day per kg body weight. The data suggest that more than one oxidative or degradative product of ascorbic acid or of some copper compounds may be responsible for the observed antitumor activities, and that the chemotherapeutic effect is being produced at some stoichiometric ratios of ascorbic acid to cupric ions. When such a combination of the two substances was consumed by the mice, optimal therapeutic effect was exerted on the implanted xenografts. PMID- 1627741 TI - Effect of atrazine on hemopoietic system. AB - For a long time some pesticides (chlordane, lindane, DDT) have been associated with bone marrow aplasia. Little is known on the toxic activity of the herbicides s-triazines on hemopoiesis. We studied the effect of one of these compounds (atrazine) on mouse hemopoietic progenitors (CFU-S and GM-CFC) and on peripheral blood (leukocytes and reticulocytes) after a single i.p. injection of 58.65 mg/kg. The peripheral blood leukocyte level was not modified; on the contrary, reticulocytes dropped severely but recovered promptly. Hemopoietic progenitors were severely hit but they recovered and reached normal levels in a few days. Our results demonstrate a hemotoxic effect of atrazine. However, more data are needed, especially in experiments with chronic exposure. PMID- 1627742 TI - Acute inflammation effects on in vivo granulopoiesis: comparative studies in healthy and leukaemic mice. AB - Mice undergoing an inflammatory reaction, induced by subcutaneous implantation of copper rods, elaborate two kinds of humoral stimulatory factors: the diffusible granulopoietic stimulator (DGS) that enhances diffusion chamber (DC) granulopoiesis, and the serum colony stimulating factor (CSF) that stimulates in vitro granulocyte-monocyte colony growth. We demonstrate here that mice suffering from acute myeloid leukaemia (AML) are unable to augment the production of these humoral stimulatory factors when acute inflammation is induced. Moreover, our results show that increased levels of normal humoral stimulatory factors (DGS and CSF) do not influence the proliferation and/or the differentiation of leukaemic cells implanted in DC. PMID- 1627743 TI - Carcinogenicity of lifelong administration of capsaicin of hot pepper in mice. AB - Capsaicin was administered in a semisynthetic powdered diet at 0.03125% level for the lifespan of Swiss mice starting from 6 weeks of age. As a result of C treatment, tumors of the cecum were induced in 22% of females and 14% of males, whereas the corresponding tumor incidences in untreated female and male controls were both 8%. Histopathologically, the tumors were classified as benign polypoid adenomas. Capsaicin is the main pungent principle of hot pepper, which is consumed in high quantities by humans worldwide. The capsaicin content of some chili varieties ranges up to 0.53%. PMID- 1627744 TI - Some physiological characteristics of (SLN X C3H/He)F1 obese mice. AB - (SLN x C3H/He)F1 mice of both sexes showed significantly heavier body weights than the parental strains associated with the higher food intake and an accumulation of adipose tissue in the subcutaneous and the abdominal regions. Furthermore, serum levels of free fatty acid and growth hormone of F1 mice were higher and lower, respectively, than those of the parental strains. The results indicate that the obesity of these F1 mice is ascribed to excess food intake and metabolic disorders and they are promising as an animal model for the study of several diseases related to obesity. PMID- 1627745 TI - Relationship between pup growth, mother weight, food or water intake in four strains of mice. AB - The partial correlation coefficients were computed between pup growth rate on day 12 of lactation and mother weight on day 11 or daily food or water intake by mother between days 4 and 11 in the 1st to 3rd lactations of four strains of mice, SHN, SLN, C3H/He and GR/A, in order to estimate the influence of food and/or water intake on lactational performance (pup growth) and mother weight. In SHN mice, pup growth rate had negative and positive correlations with food intake and mother weight, respectively, in the 1st lactation. This indicates that food ingested is used for mother weight increase rather than for lactation. On the contrary, there was a positive correlation between pup growth rate and food intake in the 3rd lactation of SHN mice and in the 2nd lactation of GR/A mice, suggesting the preferential contribution of food to lactation. In neither SLN nor C3H/He mice apparent relations between variables were seen. These results suggest the careful choice of mouse strains for studies on nutrition and lactation. PMID- 1627746 TI - Transplantation of canine malignant lymphomas in the nude and SCID mouse. AB - Canine lymphoid tumours, which share a number of features with human non Hodgkin's lymphomas, were grafted in nude or SCID mice. Two (DL.24,DL.31) out of eight lymphomas and two (DL.31,DL.35) out of three lymphomas produced a sub cutaneous (s.c.) tumour in nude and SCID mice respectively. In all animals, the s.c. tumours that developed at the inoculation site were regularly associated with metastasis to the regional lymph nodes, and also to the spleen, liver and bone marrow in SCID mice. The four transplanted tumours, with a pseudo-diploid canine karyotype, were diffuse large cell lymphomas as the initial dog tumours, and could be immunophenotypically characterized by surface immunoglobulins, MHC class 2 and Thy-1 antigens. Serially transplanted lymphomas in nude and SCID mice may hence be used for further studies of these tumours. PMID- 1627747 TI - Quantification of the sulphomucin-producing cell population of the colonic mucosa during protracted stress in rats. AB - The sulphomucins contained in goblet cells of the descending colon of 55 Sprague Dawley rats were histochemically labelled by High Iron Diamine (HID) and quantified in an image analyzer (Cortex controller). After transportation to the stress laboratory, 25 rats were compelled to swim for two consecutive hours/day either only once (5 rats), for one week (5 rats), two weeks (5 rats), four weeks (5 rats) or eight weeks (5 rats). 25 additional rats were only transported to the stress laboratory (i.e. "sham-handled" control), either once (5 rats), for one week (5 rats), two weeks (5 rats), four weeks (5 rats) or eight weeks (5 rats). The remaining 5 rats were "untransported", resting control rats (i.e. day zero). The results were expressed in percent of HID-staining/total mucosa analyzed. When various time intervals were compared with those of day zero (i.e. horizontal study), it was found that one day swimming rats had a significantly lower percentage (p less than 0.001) of HID stained material. The fluctuations at other time intervals were non-significant. On the other hand, for transported rats, a significant increase (p less than 0.001) in the percentage of HID positive areas was found for rats swimming for eight weeks. When compared to day one, the percentage of HID positive areas increased from day one to one-eight weeks, the differences being significant (p less than 0.001) at four and (p less than 0.01) eight weeks. Similar results were found for transported rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627748 TI - Oviductal glycoproteins in sexually immature mice. AB - The expression of oviductal glycoproteins was studied in prepubertal mice by lectin overlay of electrophoretically separated cellular extracts. Two N acetylgalactosamine specific lectins [Maclura pomifera (MPA), and Ricinus communis (RCA-I)] were used to study samples obtained from 7, 14, 21 and 28 day old virgin mice. A total of 9 developmentally regulated glycoprotein bands were identified. Several patterns of glycoprotein expression were noticed: glycoproteins expressed equally strongly in all stages of development; glycoproteins that were weakly expressed or not found in 7 day old or 14 and 21 day old mice but became more prominent and reached maximal expression in mature mice; glycoproteins expressed under the influence of maternal hormones at 7 days that became barely detectable in 14 and 21 day old mice but were strongly expressed in mature mice. These data show that the pattern of expression of oviductal glycoproteins changes during the prepubertal maturation of the oviduct. PMID- 1627749 TI - Relationship between preimplantation host weight and growth of the mouse adenocarcinoma EO 771. AB - Growth curves of 26 EO 771 adenocarcinomas transplanted under identical conditions into 26 syngeneic C57bl/6 male mice of the same age but with different body weight were analyzed using the method of the recursion formula of the Gompertz function. The results of this analysis were then related to the body weight of the animals at the time of tumor implantation. Although all tumors grew according to the Gompertz mode of growth, the growth curves differed from each other. Moreover, there is a statistically significant correlation between the parameters of the individual growth curves and the corresponding animal weight at the time of tumor implantation (p less than 0.025). In animals with higher body weight the tumors grew with a higher initial growth rate and subsequently with a faster growth deceleration compared to animals with lower body weight. The physiological basis for this relationship is unknown but the question arises whether this relationship also has some meaning for human malignancies. PMID- 1627750 TI - Distribution of a novel nuclear protein in normal and regenerating liver cells. AB - Monoclonal antibodies to a rat liver nuclear protein (B2, 68 kda, pI: 6.5-8.2) have been established and characterized to localize the distribution of this antigen in nuclear organization. It was demonstrated that this nuclear protein B2 is associated with actively transcribed nucleosomes and the nuclear matrix as revealed by immunogold labelling. In the regenerating liver cell, the immunogold particles are predominantly in the euchromatin as compared to the resting liver cells which are mainly in nuclear matrix and heterochromatin. It was also demonstrated that the incorporation of 32P into the nuclear protein B2 is increased 6-fold in the actively transcribed nucleosomes as compared to the nuclear matrix, as analyzed by two-dimensional polyacrylamide gel electrophoresis. We hypothesize that this nuclear protein may act as an anchorage point either for actively transcribed RNA or for DNA replication. Once this protein is highly phosphorylated, it dissociates from the nuclear envelope and can then dynamically interact with active nucleosomes within the nucleus. PMID- 1627751 TI - The renal dopamine receptors. AB - Dopamine is an endogenous catecholamine that modulates many functions including behavior, movement, nerve conduction, hormone synthesis and release, blood pressure, and ion fluxes. Dopamine receptors in the brain have been classically divided into D1 and D2 subtypes, based on pharmacological data. However, molecular biology techniques have identified many more dopamine receptor subtypes. Several of the receptors cloned from the brain correspond to the classically described D1 and D2 receptors. Several D1 receptor subtypes have been cloned (D1A, D1B, and D5) and are each coupled to the stimulation of adenylyl cyclase. The D2 receptor has two isoforms, a shorter form, composed of 415 amino acids, is termed the D2short receptor. The long form, called the D2long receptor, is composed of 444 amino acids; both are coupled to the inhibition of adenylyl cyclase. The D3 and D4 receptors are closely related to, but clearly distinct from, the D2 receptor. They have not yet been linked to adenylyl cyclase activity. Outside of the central nervous system, the peripheral dopamine receptors have been classified into the DA1 and DA2 subtypes, on the basis of synaptic localization. The pharmacological properties of DA1 receptors roughly approximate those of D1 and D5 receptors, whereas those of DA2 receptors approximate those of D2 receptors. A renal dopamine receptor with some pharmacological features of the D2 receptor but not linked to adenylyl cyclase has been described in the renal cortex and inner medulla. In the inner medulla, this D2-like receptor, termed DA2k, is linked to stimulation of prostaglandin E2 production, apparently due to stimulation of phospholipase A2. Of the cloned dopamine receptors, only the mRNA of the D3 receptor has been reported in the kidney. The DA1 receptor in the kidney is associated with renal vasodilation and an increase in electrolyte excretion. The DA1-related vasodilation and inhibition of electrolyte transport is mediated by cAMP. The role of renal DA2 receptors remains to be clarified. Although DA1 and DA2 receptors may act in concert to decrease transport in the renal proximal convoluted tubule, the overall function of DA2 receptors may be actually the opposite of those noted for DA1 receptors. Dopamine has been postulated to act as an intrarenal natriuretic hormone. Moreover, an aberrant renal dopaminergic system may play a role in the pathogenesis of some forms of hypertension. A decreased renal production of dopamine and/or a defective transduction of the dopamine signal is/are present in some animal models of experimental hypertension as well as in some forms of human essential hypertension. PMID- 1627752 TI - Studies to determine the basis for hyperkalemia in recipients of a renal transplant who are treated with cyclosporine. AB - Hyperkalemia is commonly encountered in patients who receive a renal transplant and the immunosuppressive drug, cyclosporine. There is also a high incidence of hypertension (which is thought to be due to expansion of the extracellular fluid volume) and hyperchloremic metabolic acidosis in this group of patients. This constellation of findings led to the suspicion of the possibility that their basis might be type II hypoaldosteronism. To test this hypothesis, 12 patients with hyperkalemia (plasma K+, 5.1 +/- 0.2 mmol/L at the time of study) while receiving cyclosporine were studied. Patients who had diabetes mellitus, those receiving drugs known to cause hyperkalemia (e.g., beta blockers, angiotensin converting enzyme inhibitors, K(+)-sparing diuretics), or those with a serum creatinine greater than 200 mumol/L were excluded. The renal response to hyperkalemia was inappropriate because the transtubular K+ concentration gradient (TTKG) was only 4.3 +/- 0.4 compared with a TTKG of 13 +/- 1, 2 h after 50 mmol of KCl was given to normal subjects. The TTKG, after administration of 200 micrograms of fludrocortisone, was still very low (5.6 +/- 0.6) in the patients compared with that of controls (12 +/- 1). After administration of 250 to 500 mg of acetazolamide to increase the delivery of bicarbonate to the distal nephron, the TTKG rose significantly to 11 +/- 1 in patients on cyclosporine, compared with 17 +/- 1 in the controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627753 TI - A pilot study to assess the ability of an orally available selective thromboxane synthase inhibitor to improve renal function in cyclosporine-treated renal transplant recipients. AB - Six cyclosporine (cyclosporine A [CsA])-treated renal transplant patients (4.3 +/ 0.6 months posttransplantation) were studied to see if selective urinary thromboxane (TX) inhibition with CGS 12970 (TX synthase inhibitor) would improve renal function and lessen CsA-induced decrements in RPF and GFR as measured by [99Tc]DTPA and [131I]hippuran clearances. The baseline trough CsA levels of the patients were 208 +/- 92 ng/mL. Before treatment with CGS 12970 (100 mg twice a day for 7 days), all drugs known to affect renal function or CsA pharmacokinetics were stopped. CGS 12970 therapy did not alter RPF (203 +/- 17 pre versus 200 +/- 15 mL/min post), GFR (38.5 +/- 3.2 pre versus 38.2 +/- 3.9 mL/min post), or serum creatinine (creat) (1.9 +/- .06 pre versus 1.8 +/- 0.18 mg/dL post), despite an average of 81% suppression of urine TX (65 +/- 14 pg/mg of creat pre versus 12 +/ 4 pg/mg of creat post); P less than 0.01), as measured by gas chromatography/mass spectrometry. CGS 12970 had no significant effect on urinary 6-keto-prostaglandin F1 alpha levels (63 +/- 4 pg/mg of creat pre versus 85 +/- 25 pg/mg of creat post). CGS 12970 did not alter CsA pharmacokinetics or drug levels, blood pressure, weight, or serum electrolytes of the patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627755 TI - Acquired cystic disease in chronically rejected renal transplants. AB - Acquired cystic disease has been documented to complicate most forms of chronic renal damage; it has only infrequently been described in transplanted kidneys. Five patients with noncystic ESRD and chronically rejected transplants in which acquired cystic disease arose are reported. The diagnosis of acquired cystic disease was established in examination of transplant nephrectomies from four patients and a core biopsy from the fifth. The allografts were in place from 44 to 80 months; three patients were treated with hemodialysis before the diagnosis of acquired cystic disease, whereas two received peritoneal dialysis. Three of the four patients evaluated had cysts in the native kidneys. Although papillary hyperplasia of lining epithelium was evident in four specimens, only one kidney was the site of neoplasms in the form of multiple small tubular adenomas. No malignant neoplasms were noted in this study or in the few similar previous ones; however, it is possible that chronically rejected transplanted kidneys may harbor neoplasms with the same malignant potential as those in acquired cystic disease in native kidneys. PMID- 1627754 TI - Chronic cyclosporine therapy impairs endothelium-dependent relaxation in the renal artery of the rat. AB - Cyclosporine is an immunosuppressive substance that causes structural and functional alterations in endothelial cells. To examine the effects of chronic cyclosporine therapy on endothelial function, Wistar Kyoto rats received daily s.c. injections of saline, cyclosporine solvent, or cyclosporine (15, 30, or 50 mg/kg) for up to 2 wk. Blood pressure remained unchanged in all groups. Segments of the renal artery were suspended in organ chambers filled with physiological salt solution, and isometric tension was recorded. In rats treated with 30 or 50 mg/kg/day of cyclosporine, endothelium-dependent relaxations to acetylcholine of the renal artery were significantly impaired when compared with vessels obtained from rats injected with saline or solvent. The reduced acetylcholine-induced relaxation of cyclosporine-treated vessels was improved by preincubation of the preparations with the cyclooxygenase inhibitor indomethacin. Endothelium independent relaxations in response to sodium nitroprusside were unimpaired in renal artery rings after 1 wk of cyclosporine but were reduced after 2 wk of treatment with 30 mg/kg/day. Contractions of the renal artery in response to norepinephrine and serotonin were not altered by cyclosporine. Thus, (1) high dose cyclosporine therapy impairs endothelium-dependent relaxations in the renal artery of the rat; (2) an endothelium-derived cyclooxygenase product reduces the effects of endothelium-derived relaxing factor in cyclosporine-treated rats; and (3) chronic cyclosporine treatment slightly impairs vascular smooth muscle relaxation, whereas vascular contractility remains unaltered. PMID- 1627756 TI - Potassium chloride lowers blood pressure and causes natriuresis in older patients with hypertension. AB - Epidemiologic surveys, experimental studies in animals, and clinical trials in young and middle-aged patients with hypertension indicate that dietary potassium lowers blood pressure. The mechanism of the antihypertensive effect is not well defined. Variations in serum potassium within the physiologic range may directly affect vascular smooth muscle tone. Potassium may also influence the regulation of blood pressure through effects on sodium handling, aldosterone secretion, the renin/angiotensin system, renal kallikrein, eicosanoids, and atrial natriuretic peptide. This study was undertaken to confirm the blood pressure-lowering effect of potassium in older patients and to determine the mechanism of the antihypertensive effect. Twenty-two patients greater than or equal to 60 yr of age were admitted to a Clinical Research Unit for 8 days after a 2-wk period free of antihypertensive medication. Patients were placed on an isocaloric diet containing 200 mmol/day of Na+, 70 mmol/day of K+, and 500 mg/day of Ca2+ and were treated in a randomized, double-blinded manner with either potassium chloride (120 mmol/day) or placebo. After 4 days, patients were crossed over to the alternate treatment. Systolic blood pressure decreased 8.6 mm Hg (95% confidence interval -14.6, -2.6), and diastolic blood pressure decreased 4.0 mm Hg (-6.9, -1.0) during potassium chloride supplementation. There was no significant change in blood pressure during treatment with placebo. Serum K+ was 3.9 +/- 0.1 mmol/L after 3 days of placebo and 4.3 +/- 0.1 after 4 days of potassium chloride (P less than 0.002). Urinary sodium excretion averaged 192 +/- 11 mmol/day after placebo and 221 +/- 8 after potassium treatment (P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627757 TI - Idiopathic Fanconi syndrome in a family. Part I. Clinical aspects. AB - Fanconi syndrome is a rare cause of rickets in children. Only six families with Fanconi syndrome following an autosomal dominant pattern of inheritance have been reported. In this report, the results of clinical studies performed in three generations of a family of 39 members with autosomal dominant Fanconi syndrome are presented. Twenty-one members of this family provided blood and urine for biochemical evaluation. Many family members have one or more tubular reabsorptive abnormalities; however, the complete Fanconi syndrome was not present in most members. Three children with the complete syndrome all occur in the last generation. When the characteristic features of this family were compared with those of previously reported families with autosomal dominant Fanconi syndrome, several differences became apparent. Two serious manifestations, diabetes mellitus and renal failure, which occur in previous reports did not occur in this family. This report provides information on apparently the largest number of affected individuals in a single family with Fanconi syndrome. In addition, variable expressivity of tubular reabsorptive defects in a family with Fanconi syndrome has never been reported. PMID- 1627758 TI - Protective effects of glutathione, glycine, or alanine in an in vitro model of renal anoxia. AB - Both glutathione and glycine provide some protection against ischemic renal injury in a variety of experimental models. However, results have been inconsistent and there may also be model heterogeneity. The effects of glutathione, glycine, and alanine in a cell culture model of renal anoxia/reoxygenation injury were tested. When primary cultures of rat proximal tubule epithelial cells were subjected to 60 min of anoxia and 30 min of reoxygenation, glutathione (2 mM) essentially eliminated lethal cell injury as determined by lactate dehydrogenase release. Glycine or alanine, on the other hand, provided only partial protection. Glutamate did not protect, although cysteine did. The glutathione synthesis inhibitor buthionine sulfoximine blocked the protective effect of exogenous glutathione, and the glutathione transport inhibitor probenecid partially blocked glutathione protection. A combination of glycine, glutamate, plus cysteine also protected against anoxia/reoxygenation injury. The studies suggest that both glutathione degradation with intracellular resynthesis and transport of intact glutathione into the cell are involved in the protection afforded by exogenous glutathione. These results are different from those obtained in other experimental models of renal ischemia, such as freshly isolated proximal tubules, because the protective effects of glutathione were not derived solely from glycine generation. These studies also suggest the need for caution in extrapolating results from one model of renal anoxic injury to another. PMID- 1627759 TI - Murine monoclonal anti-DNA antibodies penetrate cells, bind to nuclei, and induce glomerular proliferation and proteinuria in vivo. AB - The production of relatively high quantities of autoantibodies (autoAb) that react with DNA and other intranuclear antigens is characteristic of individuals with systemic lupus erythematosus and other autoimmune diseases. However, the capacity of these Ab to penetrate cells and induce functional perturbations in vivo is not well appreciated. To address this issue, monoclonal (m) anti-DNA Ab (mAb), derived from MRL-lpr/lpr and (NZB x SWR)F1 mice, were administered to normal mice, and the animals were examined for morphologic and functional abnormalities. A subset of five mAb produced intranuclear immunoglobulin deposits in multiple organs. Intranuclear immunoglobulin deposits were also observed after cross-linking the tissue before direct immunofluorescence and after i.v. injection of F(ab')2 fragments of one anti-DNA Ab. This phenomenon was reproducible and was only associated with this subset of autoAb. Furthermore, intranuclear deposits of anti-DNA Ab within glomeruli were associated with morphologic and functional abnormalities including: hypercellularity, epithelial foot process fusion, new fiber bundle formation within the mesangium suggestive of new collagen synthesis, and proteinuria. These results indicate that a subset of autoAb may penetrate cells in vivo to influence normal cellular and nuclear function and to contribute to functional and pathologic abnormalities in individuals with systemic lupus. PMID- 1627760 TI - Thyroid hormone, L-T3, stimulates the expression of the angiotensinogen gene in cultured opossum kidney (OK) cells. AB - Angiotensinogen (ANG) messenger RNA is expressed in opossum kidney (OK) proximal tubular cells. To examine whether thyroid hormone, L-T3, could stimulate the expression of the ANG gene in OK proximal tubular cells, fusion genes, consisting of various lengths of the 5'-flanking region of the rat angiotensinogen gene linked to a human growth hormone reporter gene, were constructed and introduced into OK cells. As a negative control, they were introduced into a nonkidney cell line, a human choriocarcinoma cell line (JEG-3). The level of the expression of fusion genes in these cells were determined by the level of immunoreactive human growth hormone secreted into the culture medium. The expression of ANG-growth hormone (ANG-GH) fusion genes pOGH (ANG N-1498/+18), pOGH (ANG N-688/+18), pOGH (ANG N-110/+18), pOGH (ANG N-53/+18), and pOGH (ANG N-35/+18) was 226-, 4.5-, 1.0 , 12-, and 2.5-fold higher than promoterless pOGH in the expression of growth hormone activity in OK cells. No significant expression of any of these ANG-GH fusion genes over the promoterless pOGH was observed in JEG-3 cells. The addition of L-T3 stimulates the expression of pOGH (ANG N-1498/+18) in a dose-dependent manner with a maximal and half-maximal effect at 10(-7) M and at 10(-8) to 10(-9) M, respectively. Thyroid hormone (10(-7) M) also stimulates the expression of pOGH (ANG N-688/+18) but not pOGH (ANG N-110/+18), pOGH (ANG N-53/+18), or pOGH (ANG N-35/+18).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627761 TI - Role of the endothelium-dependent relaxing factor nitric oxide on renal function. AB - The role of nitric oxide in renal function has been assessed with pharmacologic and physiologic interventions. Pharmacologically, the renal vasodilation and, to some extent, the natriuresis produced by endothelium-dependent vasodilators such as acetylcholine and bradykinin are mediated by nitric oxide and also by prostaglandins. However, prostaglandins and nitric oxide do not participate in the renal effects produced by endothelium-independent vasodilators such as atrial natriuretic peptide, prostaglandin I2, and nitroprusside. Physiologically, nitric oxide and prostaglandins exert a strong regulation on the effects produced by changes in renal perfusion pressure. Increments in renal perfusion pressure within the range of RBF autoregulation appear to inhibit prostaglandin synthesis while simultaneously enhancing the formation of nitric oxide. Nitric oxide modulates autoregulatory vasoconstriction and at the same time inhibits renin release. Conversely, a decrease of renal perfusion pressure to the limit of or below RBF autoregulation may inhibit the synthesis of nitric oxide but may trigger the release of prostaglandins, whose vasodilator action ameliorates the fall in RBF and stimulates renin release. Nitric oxide and prostaglandins are also largely responsible for mediating pressure-induced natriuresis. However, unlike prostaglandins, mild impairment of the synthesis of nitric oxide in systemic circulation produces a sustained decrease in sodium excretion, which renders blood pressure susceptible to be increased during high-sodium intake. This effect suggests that a deficiency in the synthesis of nitric oxide could constitute the most effective single disturbance to foster the development of a syndrome similar to that seen in salt-sensitive hypertension. PMID- 1627762 TI - Glomerular epithelial cells secrete a glomerular basement membrane-degrading metalloproteinase. AB - Cultured rat glomerular epithelial cells (GEC) were examined for their ability to release extracellular matrix-degrading proteinases with [3H]gelatin as substrate. GEC-conditioned media, under serum-free conditions, contained modest amounts of gelatinase activity (1 to 10 U/mg of protein); the activity was maximal at neutral pH, was inhibited by zinc chelators, was not inhibited by tissue inhibitor of metalloproteinase-2, and could not be further activated by trypsin or organomercurials. Gelatin substrate sodium dodecyl sulfate-polyacrylamide gels of GEC-conditioned medium revealed several zones of lysis, with molecular sizes of 150 kd (major band), and 220, 86 to 93, and 52 to 54 kd (minor bands). Northern blot analysis demonstrated that the GEC metalloproteinase(s) were distinct from the 68- to 72-kd type IV collagenase/gelatinase present in mesangial cells or the 92-kd type IV collagenase present in neutrophils. The GEC gelatinolytic activity also degraded insoluble type IV collagen in glomerular basement membrane in a dose-dependent manner. The major metalloproteinase activity responsible for the type IV collagen degradation has a molecular size of 150 kd with a type IV collagen substrate gel. Thus, GEC produce several neutral metalloproteinases, which, by virtue of their substrate specificity, may play an important role in glomerular basement membrane remodeling and in glomerular diseases characterized by alterations in basement membrane permeability. PMID- 1627763 TI - Clinical pharmacology and economics of recombinant human erythropoietin in end stage renal disease: the case for subcutaneous administration. AB - The clinical pharmacology of human recombinant erythropoietin (epoetin) was studied in order to compare the effectiveness of various routes and dosing schedules in dialysis patients. Thirty-six patients received epoetin beta three times a week i.v. for at least 12 wk. The mean dose needed to achieve target hemoglobin was 225 +/- 36 U/kg per week (median dose, 180 U/kg per week). Twenty eight of 36 patients who were converted to a once-a-week i.v. schedule increased their requirements to 429 +/- 50 U/kg per week in order to maintain a target hematocrit of 33 to 40 vol%. Twelve of 28 patients could maintain their target hematocrit when dosed once a week s.c. at 84 +/- 10 U/kg. The other 16 patients required 137 +/- 15 U/kg per week divided into two doses. In the entire group of 28 patients, the weekly requirement for epoetin was reduced by 50% when the s.c. route was used two or three times a week. Pharmacokinetic studies performed during chronic therapy indicated rapid clearance of erythropoietin (t1/2 of 6.8 +/- 0.3 h). Single i.v. doses greater than 150 U/kg were required to increase basal erythropoietin by 30 mU/mL at 44 h postdosing. With s.c. dosing, such increments in erythropoietin levels frequently persisted beyond 60 h because of prolonged and slow absorption. Pharmacokinetic simulations in conjunction with clinical correlation of the erythropoietic response suggest that the duration that the erythropoietin levels are maintained, and not the absolute peaks, is the primary determinant of efficacy. This may result from nonlinearity in the dose response. Pharmacokinetic simulation also indicated that i.v. dosing could not maintain adequate interdialytic erythropoietin levels, whereas s.c. dosing could. Cost analysis indicated that the use of s.c. dosing two or three times a week at an average total weekly dose of 110 to 120 U/kg is effective treatment of anemia in most dialysis patients. PMID- 1627764 TI - Dopamine enhances the phosphaturic response to parathyroid hormone in phosphate deprived rats. AB - Phosphate deprivation results in a resistance to the phosphaturic effect of parathyroid hormone. Dopamine is phosphaturic and is synthesized by kidney proximal tubule, the nephron subsegment where parathyroid hormone inhibits phosphate transport. Thus, to test the hypothesis that phosphate deprivation is associated with low intrarenal dopamine synthesis and that dopamine infusion will overcome the resistance to the phosphaturic response to parathyroid hormone, the following study was performed. The effect of dietary phosphate intake on intrarenal dopamine synthesis, as reflected by urinary dopamine excretion, was determined. Rats were placed in metabolic cages (N = 5) and were fed a low phosphate diet (0.07% Pi) for 4 days and then a high-phosphate diet (1.8% Pi) for 4 days. Twenty-four-hour urinary dopamine excretion was significantly lower in rats fed a low-phosphate diet (2.53 +/- 0.06 versus 4.10 +/- 0.30 micrograms/day). Further, the effect of dopamine infusion on the blunted phosphaturic response to parathyroid hormone was studied in rats fed a low phosphate diet for 1, 2, and 3 days. Control clearances were taken 2 h after thyroparathyroidectomy; then, parathyroid hormone (33 U/kg plus 1 U/kg/min), dopamine (25 micrograms/kg/min), or parathyroid hormone plus dopamine were infused for 60 min. Changes in the fractional excretion of phosphate were significantly greater in rats fed a low-phosphate diet infused with parathyroid hormone plus dopamine than in rats fed a low-phosphate diet infused with parathyroid hormone alone (delta 27.9 +/- 5.8 versus 11.2 +/- 2.6% for day 1; 28.4 +/- 1.4 versus 7.1 +/- 3.6% for day 2; and 10.7 +/- 2.8 versus -0.2 +/- 0.2% for day 3; N = 5 for all groups).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627765 TI - Clinical outcome of continuous ambulatory peritoneal dialysis predicted by urea and creatinine kinetics. AB - The effectiveness of urea kinetics (Kt/V, where K is urea clearance, t is treatment time, and V is the volume of distribution for urea) to assess the adequacy of continuous ambulatory peritoneal dialysis (CAPD) and clinical outcome has not been established prospectively, and cross-sectional clinical studies have been inconclusive. A minimum weekly creatinine clearance of 40 to 50 L is recommended, but the adequacy of this dose is unproven. We introduced a simpler approach to creatinine kinetics in the form of an efficacy number (EN) calculated from data obtained in a standardized 4-h dwell exchange. To determine the most effective model for predicting CAPD adequacy, residual renal function, weekly Kt/V urea, weekly creatinine clearance standardized to body surface area, and EN (liters per gram of creatinine per day) were measured in 18 stable CAPD patients followed prospectively for at least 12 months. Patients were divided into three groups, good (G), intermediate (I), and poor (P), on the basis of uremic symptoms, mortality, hospital days, biochemical indices, and the need for transfer to hemodialysis. When comparing groups G (N = 6) and P (N = 8), weekly Kt/V were 2.3 +/- 0.2 versus 1.5 +/- 0.1 (P less than 0.005), weekly creatinine clearances were 71.5 +/- 8.6 versus 35.1 +/- 1.3 L (P less than 0.001), and EN were 7.4 +/- 0.8 versus 3.6 +/- 0.2 L/g of creatinine/day (P less than 0.005). Creatinine kinetics (weekly clearance and EN) but not urea kinetics could differentiate group I (N = 4) from groups G or P. Both urea and creatinine kinetics predict clinical outcome in CAPD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627766 TI - Pyrogenic reactions in patients receiving conventional, high-efficiency, or high flux hemodialysis treatments with bicarbonate dialysate containing high concentrations of bacteria and endotoxin. AB - High-efficiency (HE) and high-flux (HF) hemodialysis are becoming increasingly popular methods for treating patients with chronic renal failure because they reduce the time required for dialysis treatment. HF and HE dialyzers require bicarbonate dialysate, often prepared from concentrates that can support bacterial growth with endotoxin production. There is a concern that endotoxins or bacteria may cross or interact at the membranes of these dialyzers, triggering the release of endogenous pyrogens (cytokines) by peripheral blood mononuclear cells to cause pyrogenic reactions (PR). To determine the incidence of PR and to examine the association between PR and levels of bacteria and endotoxin in dialysate, a cohort of patients receiving conventional, HE, or HF hemodialysis with bicarbonate dialysate and reprocessed dialyzers at three dialysis centers during a 12-month period was studied prospectively. All dialyzers underwent a test of membrane integrity before use. A total of 19 PR were identified among 18 patients in 26,877 hemodialysis treatments (0.7 PR/1,000 treatments). There was no significant difference in PR rates by treatment modality: conventional, 0.5 per 1,000 (7 PR/13,123 treatments) versus HE, 0.9 per 1,000 (9 PR/11,345) versus HF, 1.2 per 1,000 (3 PR/2,409) (P = 0.21; chi 2 test). Throughout the study period, bacterial counts for dialysate at each center significantly exceeded the Association for the Advancement of Medical Instrumentation's (AAMI) microbiologic standards for dialysate of less than 2,000 CFU/mL (mean, 19,000 CFU/mL), but water used in the reuse of dialyzers tested less than 200 CFU/mL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627767 TI - Removal of plasma porphyrins with high-flux hemodialysis in porphyria cutanea tarda associated with end-stage renal disease. AB - Plasma porphyrin levels are markedly increased in patients with porphyria cutanea tarda (PCT) associated with end-stage renal disease. Conventional hemodialysis (CHD) with lower blood flow rates (less than 250 mL/min) and cuprophan or cellulose acetate membranes is ineffective in removing significant amounts of porphyrins in this condition. Changes in plasma porphyrin levels and porphyrin clearances during hemodialysis with higher blood flow rates and more-permeable, high-efficiency cellulose acetate and high-flux polysulfone dialyzers were evaluated in a chronic hemodialysis patient with PCT and markedly elevated plasma porphyrins. The polysulfone membrane achieved significantly better fractional porphyrin removal (P = 0.02) and porphyrin clearances (P less than 0.01) than did the high-efficiency cellulose acetate membrane. After conversion from maintenance CHD with a standard cellulose acetate dialyzer to a 4-wk period of high-flux hemodialysis (HFHD) with a polysulfone dialyzer, predialysis plasma porphyrins fell by 37%. After returning to CHD, plasma porphyrins returned to the higher prestudy levels. These observations suggest that HFHD with more permeable membranes and higher blood flow rates removes porphyrins more effectively than does CHD. HFHD may be a useful adjunct to other measures used in treating dialysis patients with PCT. PMID- 1627768 TI - Acute plasma separation with hemodialysis equipment. AB - Although plasma separation has been reported to have a relatively small complication rate in large series of healthy outpatients, little attention has been directed to the evaluation of the safety and effectiveness of the therapy in acutely ill, hospitalized patients. The experience of using standard hemodialysis equipment and membrane plasma separators with 281 plasma separation treatments in 49 patients over the last 7 yr is reported and analyzed. The data reveal a 1.4% incidence of hypotension and a 0.4% incidence of hematuria in the 281 treatments- rates similar to those reported in outpatients. In addition, analysis of the diseases and patients treated over the 7 yr reported demonstrates a marked shift from immunological and hematological disorders towards neurological disorders. The data suggest that plasma separation may be easily and safely performed by any institution capable of performing acute hemodialysis. PMID- 1627769 TI - MNF1, a leaf tissue-specific DNA-binding protein of maize, interacts with the cauliflower mosaic virus 35S promoter as well as the C4 photosynthetic phosphoenolpyruvate carboxylase gene promoter. AB - When gel shift assays were performed with maize nuclear extract and a DNA fragment containing the cauliflower mosaic virus (CaMV) 35S promoter, three DNA protein complexes were observed. Analyses with nuclear extracts prepared from green leaves, etiolated leaves, stems and roots showed that the complexes resulted from the existence of at least two nuclear factors. One of them is presumably a constitutive nuclear factor found in all tissues tested, and another is a leaf-specific factor present both in green and etiolated leaves. This leaf specific nuclear factor seemed to be identical to MNF1, previously identified as a factor interacting with the promoter of the maize gene for phosphoenolpyruvate carboxylase involved in the C4 photosynthesis. Deletion analysis revealed that MNF1 binds to the sequence from -281 to -235 relative to the transcription start site of the CaMV 35S promoter. MNF1-like nuclear protein was also found in tobacco nuclear extracts. The possibility that MNF1 participates as a positive trans-acting factor in the expression of genes in maize leaves is discussed. PMID- 1627770 TI - Characterisation of a wound-induced transcript from the monocot asparagus that shares similarity with a class of intracellular pathogenesis-related (PR) proteins. AB - We report the isolation and characterisation of a wound-induced cDNA designated AoPR1 from a suspension of mesophyll cells that had been mechanically isolated from cladodes of light-grown Asparagus officinalis seedlings by grinding in a mortar and pestle. The transcript abundance is up-regulated following cell separation and in chopped mesocotyl tissue from dark-grown seedlings. The expression of AoPR1 was shown by northern analysis to be located around the site of damage. Sequence analysis revealed similarity between the predicted AoPR1 polypeptide and bean PvPR1 and PvPR2 proteins, the potato pSTH2 protein, the pea PI49 protein, the parsley PcPR1-1 protein and a major pollen allergen from birch (BetvI). These transcripts have been shown to be induced in response to microbial attack or fungal elicitation. To our knowledge, this is the first example of a monocot cDNA belonging to this class of intracellular pathogenesis-related proteins (IPRs). PMID- 1627771 TI - Iron induces ferritin synthesis in maize plantlets. AB - The iron-storage protein ferritin has been purified to homogeneity from maize seeds, allowing to determine the sequence of the first 29 NH2-terminal amino acids of its subunit and to raise specific rabbit polyclonal antibodies. Addition of 500 microM Fe-EDTA/75 microM Fe-citrate to hydroponic culture solutions of maize plantlets, previously starved for iron, led to a significant increase of the iron concentration of roots and leaves, albeit root iron was mainly found associated with the apoplast. Immunodetection of ferritin by western blots indicated that this iron treatment induced ferritin protein accumulation in roots and leaves over a period of 3 days. In order to investigate this induction at the ferritin mRNA level, various ferritin cDNA clones were isolated from a cDNA library prepared from poly(A)+ mRNA isolated from roots 48 h after iron treatment. These cDNAs were classified into two groups called FM1 and FM2. Upstream of the sequence encoding the mature ferritin subunit, both of these cDNAs contained an in-frame coding sequence with the characteristics of a transit peptide for plastid targeting. Two members of the FM1 subfamily, both partial at their 5' extremity, were characterized. They are identical, except in their 3' untranslated region: FM1A extends 162 nucleotides beyond the 3' terminus of FM1B. These two mRNAs could arise from the use of two different polyadenylation signals. FM2 is 96% identical to FM1 and contains 45 nucleotides of 5' untranslated region. Northern analyses of root and leaf RNAs, at different times after iron treatment, revealed ferritin mRNA accumulation in response to iron. Ferritin mRNA accumulation was transient and particularly abundant in leaves, reaching a maximum at 24 h. The level of ferritin mRNA in roots was affected to a lesser extent than in leaves. PMID- 1627772 TI - Dark-induced accumulation of a basic pathogenesis-related (PR-1) transcript and a light requirement for its induction by ethylene. AB - A gene encoding a basic-type pathogenesis-related protein from Nicotiana tabacum (prb-1b) was cloned, sequenced and characterized. It contains an open reading frame of 179 amino acids that is ca. 65% homologous with the acidic PR-1 class of pathogenesis-related proteins and 87% homologous with a different basic-type PR-1 gene. In the light, physiological levels of ethylene rapidly (1 h) induced basic, but not acidic-type, PR-1 transcript. Additional elicitors acting via ethylene, such as alpha-aminobutyric acid, were shown to induce basic- and acidic-type PR-1 transcript accumulation in a light-dependent manner. In contrast, xylanase, an ethylene-independent elicitor, induced transcript accumulation of basic- and acidic-type PR-1 in a light-independent manner. Dark-induced accumulation of basic PR-1 transcript occurred at night in greenhouse-grown plants and, to a greater extent, in continuously dark-treated plants. The novel dark regulation may point to additional nonpathogenesis-related roles for these genes in plant environment interactions. PMID- 1627773 TI - Mutational analysis of the 'conserved region' of maize streak virus suggests its involvement in replication. AB - Maize streak virus as well as other geminiviruses contain a potential hairpin structure with the conserved sequence TAATATTAC in the loop. We assessed the possible involvement of this structure in replication and symptom induction of the virus. A series of insertion and deletion mutants were analyzed by agroinfection. Deletion of the hairpin or insertions in the conserved sequence abolished symptom development. Viral DNA could not be detected in the infected tissue. However, a mutant with a point mutation in the 'conserved' sequence, isolated after inoculation of maize plants with an insertion mutant, was able to replicate and to induce symptoms. PMID- 1627774 TI - The isolation and characterisation of the tapetum-specific Arabidopsis thaliana A9 gene. AB - The Brassica napus cDNA clone A9 and the corresponding Arabidopsis thaliana gene have been sequenced. The B. napus cDNA and the A. thaliana gene encode proteins that are 73% identical and are predicted to be 10.3 kDa and 11.6 kDa in size respectively. Fusions of an RNase gene and the reporter gene beta-glucuronidase to the A. thaliana A9 promoter demonstrated that in tobacco the A9 promoter is active solely in tapetal cells. Promoter activity is first detectable in anthers prior to sporogenous cell meiosis and ceases during microspore premitotic interphase. The deduced A9 protein sequence has a pattern of cysteine residues that is present in a superfamily of seed plant proteins which contains seed storage proteins and several protease and alpha-amylase inhibitors. PMID- 1627775 TI - The heat shock response of pollen and other tissues of maize. AB - While a heat shock treatment of 40 degrees C or 45 degrees C induced the vegetative tissues of maize to produce the typical heat shock proteins (HSPs), germinating maize pollen exposed to the same temperatures did not synthesize these characteristic HSPs. Comparison of RNA accumulation in shoot and tassel tissue showed that mRNAs for HSP70 and HSP18 increased several-fold, reaching high levels within 1 or 2 hours. At the higher temperature of 45 degrees C these vegetative tissues were blocked in removal of an intron from the HSP70 mRNA precursor, which accumulated to a high level in tassel tissue. In germinating pollen exposed to heat shock, mRNAs for these HSPs were induced but accumulated only to low levels. The stressed pollen maintained high levels of RNA for alpha tubulin, a representative normal transcript. It is likely that the defective heat shock response of maize pollen is due to inefficient induction of heat shock gene transcription. PMID- 1627776 TI - Structure and expression during the germination of rice seeds of the gene for a carboxypeptidase. AB - The carboxypeptidase gene from rice and corresponding cDNA clones were isolated. The Sal I 11.2 kb fragment of DNA cloned from a size-fractionated genome library contained eight introns and an open reading frame that encoded 500 amino acids (M(r) 55,445). The structure deduced for the carboxypeptidase from rice was very similar to those of type III serine carboxypeptidases from barley and wheat. The extent of homology of the amino acid sequence to that of these carboxypeptidases from barley and wheat was 92.3% and 87.2%, respectively. The accumulation of mRNA for the rice carboxypeptidase was conspicuous in germinating endosperms that contained aleurone layers, but levels were lower in leaves and roots. The abundance of the mRNA in endosperms was enhanced by gibberellic acid (GA) and accumulation of the mRNA was inhibited by abscisic acid (ABA). The rice gene for carboxypeptidase contained some pyrimidine boxes (C/TCTTTTC/T), in the 5' flanking region, which are a characteristic of a GA-responsive gene. PMID- 1627777 TI - Suppression of gene expression in plant cells utilizing antisense sequences transcribed by RNA polymerase III. AB - Inverted sequences of the chloramphenicol acetyltransferase (CAT) reporter gene were fused to a soybean tRNA(met(i)) gene lacking a terminator such that the tRNA(met(i)) sequences caused the co-transcription of CAT antisense sequences by RNA polymerase III. When electroporated into carrot protoplasts, these antisense DNA constructs suppressed CAT enzyme activity expressed from co-electroporated DNAs containing the CAT gene downstream of the cauliflower mosaic virus (CaMV) 35S RNA promoter. Our most effective construct, an antisense sequence complementary to the 3' portion of the CAT gene, inhibited CAT activity five-fold greater than an antisense construct expressed by RNA polymerase II from the cauliflower mosaic virus 35S RNA promoter. These results indicate that antisense sequences transcribed by RNA polymerase III should efficiently suppress gene expression in plants. PMID- 1627778 TI - Structure and expression of the Arabidopsis CaM-3 calmodulin gene. AB - Genomic and cDNA sequences encoding a calmodulin (CaM) gene from Arabidopsis (ACaM-3) have been isolated and characterized. ACaM-3 represents a sequence distinct from two previously isolated Arabidopsis CaM cDNA clones. A 2.3 kb Eco RI restriction fragment was sequenced and found to encode a complete CaM-coding sequence interrupted by a single 491 bp intron, together with 750 bp and 600 bp of 5' and 3' flanking sequences, respectively. The polypeptide encoded by ACaM-3 is identical to that encoded by ACaM-2 and it differs from the one encoded by ACaM-1 by four of 148 residues. The putative promoter of ACaM-3 was atypical of CaM genes previously isolated from animals in that it contained consensus TATA and CAAT box sequences and lacked GC-rich regions. Two DNA sequence elements closely resembling cyclic AMP regulatory elements, which have been identified in animal CaM genes, were located in the 5' flanking region of ACaM-3. Northern blot and polymerase chain reaction amplification assays confirmed that each of the three ACaM mRNAs were expressed in similar but distinct patterns in different organs. ACaM-1 mRNA was the only species detectable in root RNA fractions, and ACaM-3 mRNA could not be detected in floral stalks. Accumulation of the three CaM mRNAs in leaves was induced by a touch stimulus, but the kinetics and extent of the induction varied among the three mRNA species. Run-on transcription assays indicated that a portion of the differences in accumulation of ACaM-1, 2, and 3 mRNAs in leaves and siliques was attributable to differences in their net rates of transcription. PMID- 1627779 TI - Mutational analysis of a plant heat shock element. AB - A total of 32 mutations were generated within the TATA-proximal site 1 (-72 to 47) of soybean heat shock gene Gmhsp17.5E in order to functionally define the optimal configuration of sequences within the heat shock element (HSE). Mutants were tested in vivo utilizing sunflower tumors transformed by a T-DNA based vector. Promoter activity was determined by S1 nuclease hybrid protection analysis of tumor transcripts. A total of five repeats (5'-nGAAn-3' or 5'-nTTCn 3') which comprise the HSE at site 1 were required for full transcription induction by heat stress. Analysis of non-conserved bases flanking the central trinucleotide block indicated that 5'-aGAAg'-3' is the optimum sequence for the 5 bp repeat. PMID- 1627780 TI - Structure and expression of kin2, one of two cold- and ABA-induced genes of Arabidopsis thaliana. AB - We report the isolation of the second member, kin2, of a family of two cold inducible genes of Arabidopsis thaliana. The proteins corresponding to the two genes have similarities to the small antifreeze proteins from Winter flounder. Kin1 and kin2 are organized in a close tandem array in the genome of A. thaliana. Both have three exons separated by introns with approximately the same length and location. The coding regions are highly conserved while the introns and especially the 3' flanking sequences of the mRNAs have diverged. The kin1 and kin2 genes are coordinately regulated in the cold. Unlike kin1, the kin2 mRNA has a detectable basal level, and accumulates to a higher level during acclimation. Both mRNAs are induced by 10 microM ABA but only kin2 responds strongly to drought and salinity stresses. PMID- 1627781 TI - Identification and characterization of a hypoxically induced maize lactate dehydrogenase gene. AB - In cereal root tissue, hypoxia induces the enzyme lactate dehydrogenase (LDH); (S)-lactate:NADH oxidoreductase, EC 1.1.1.27). In barley, both biochemical and genetic data indicate that five isozymes are induced under hypoxia. These isozymes are tetramers and arise from the random association of the products of two Ldh genes. The induction of LDH activity in root tissue has been shown to be correlated to an increase in LDH protein and Ldh mRNA. In order to more fully characterize the hypoxic induction of LDH, we have isolated a maize Ldh genomic clone which has strong homology at both the amino acid and nucleotide level to the barley LDH cDNA clones. The Ldh1 gene consists of two exons separated by a 296 bp intron, has the expected eukaryotic regulatory signals and a sequence that has strong homology to the maize anaerobic regulatory element. PMID- 1627782 TI - A barley cDNA clone encoding a type III chlorophyll a/b-binding polypeptide of the light-harvesting complex II. AB - The nucleotide sequence of a leaf cDNA clone encoding a Type III chlorophyll a/b binding (CAB) protein of light-harvesting complex II (LHCII) in barley is reported. Sequence comparisons and results from in vitro import into chloroplasts demonstrate that the cDNA clone encodes a functional transit peptide of 45 amino acid residues and a mature polypeptide of 223 residues with a predicted molecular mass of 24.3 kDa. After insertion into thylakoids, the mature protein is resistant to protease attack. Hybridization analysis using a gene-specific probe shows that the gene is expressed in dark-grown seedlings and that the amount of mRNA increases during illumination. PMID- 1627783 TI - Nucleotide sequence of a gene for an endopeptidase (EP-C1) from Phaseolus vulgaris. PMID- 1627784 TI - Nucleotide sequence of a cDNA encoding a lipid transfer protein from wheat (Triticum durum Desf.). PMID- 1627785 TI - Nucleotide sequence of a cDNA clone encoding a precursor to stearoyl-(acyl carrier-protein) desaturase from spinach, Spinacia oleracea. PMID- 1627786 TI - Tumor necrosis factor and interferon gamma: relevance for immune regulation and genetic predisposition to autoimmune disease. AB - The role of TNF-alpha and IFN-gamma in various models of autoimmune disease were analyzed. These include murine models of lupus, type 1 diabetes in NOD mice and the adjuvant arthritis model in rats. Rather than being involved mainly in the effector arm of the inflammatory process of autoimmune organ destruction, our data suggest a primary involvement of these cytokines in some of the basic mechanisms of the autoimmune process. Evidence has been presented that emphasizes the possibility of the involvement of TNF-alpha in the genetic predisposition to SLE. Based on the data presented, one should be cautious in extrapolating the effects of these cytokines in various in vitro systems to the in vivo situation. PMID- 1627787 TI - Interleukin-6 in autoimmune disorders. AB - Interleukin-6, a pleiotropic cytokine, appears to play a key role as a physiologically functioning molecule in host defense mechanisms. Previous reports have suggested that dysregulated interleukin-6 production may be involved in lymph node hyperplasia, plasmacytosis, immunoglobulin hyperproduction, thrombocytosis, mesangial cell proliferation and acute phase response, all of which are frequently observed in autoimmune disorders. In this report, we discuss the possible involvement of interleukin-6 in the pathogenesis of a variety of autoimmune diseases and the regulatory mechanism of expression of the interleukin 6 gene. PMID- 1627788 TI - Interleukin-2, a pro-autoimmune lymphokine that interferes with post-deletional tolerance. AB - Various complementary mechanisms arranged in a fail-safe hierarchy impede the immune system from launching auto-aggressive attacks, namely intrathymic or post thymic clonal deletion, anergy, and immunosuppression. Both epidemiological and clinical evidence demonstrates that interleukin-2 (IL-2) may exert a pro autoimmune effect. Thus, IL-2 reverses immunological tolerance in determined in vitro or in vivo circumstances, is produced at abnormally high levels in certain autoimmune diseases, and induces organ-specific autoimmune lesions when administered to patients. To unravel the molecule and cellular mechanisms responsible for the pro-autoimmune nature of IL-2, our group has employed a recombinant hIL-2 vaccinia virus construct (IL-2. VV) as a self-replicating IL-2 releasing device that may be administered as a source of exogenous IL-2 to experimentally manipulated mice. IL-2 does not interfere with clonal deletion of potentially autoreactive T cells in the thymus since application of IL-2. VV to young mice fails to augment the frequency of T cells bearing 'forbidden' T cell receptor (TCR) V beta gene products (i.e. T cells that recognize endogenous retroviral superantigens). Along the same line, IL-2. VV does not reverse the clonal deletion in male mice bearing a male-specific transgenic alpha/beta TCR that undergo depletion of CD4+ CD8+ thymocytes, nor does it abolish post-thymic clonal deletion of V beta 8+ T cells reactive with the bacterial superantigen Staphylococcus aureus enterotoxin B (SEB). In contrast with its incapability to abolish intra- and post-thymic elimination of T cells with unwarranted specificities, IL-2 abrogates anergy of T cells. Non-deleted, 'forbidden' T cells from congenitally athymic or neonatally thymectomized mice, under normal circumstances anergic, become responsive to TCR-triggering and mediate a systemic autoimmune syndrome upon IL-2. VV treatment. Thus, IL-2 appears to interfere with T cell tolerance at a post-deletional stage, reversing functional non responsiveness and enabling non-deleted T cells that bear a potentially autoreactive TCR repertoire to cause manifest autoimmunity. PMID- 1627789 TI - Does interleukin-2 abrogate peripheral immunologic self-tolerance in vivo? AB - Transgenic mice that constitutively expressed murine IL-2 in islet beta cells (RIP-IL-2 mice) had pancreatitis from birth which resolved into a peri- and intra islet infiltrate in adult animals. In spite of the impressive infiltration, these mice did not develop autoimmunity to islet antigens. Neither was autoimmunity found to extrathymic H-2Kb molecules known to induce tolerance by a peripheral mechanism, when IL-2 and H-2Kb were coexpressed in the beta cells. Apparently, IL 2 can only act on activated T cells and is unable to reverse tolerance in T cells that have been made unresponsive through inappropriate antigen presentation in our system. PMID- 1627790 TI - Prevention of B cell clonal deletion and anergy by activated T cells and their lymphokines. AB - B cell tolerance is described as the absence of a measurable antibody forming response to an antigenic challenge. The establishment of antigen-specific tolerance requires, by definition, engagement of the B cell antigen-specific receptor. However, only in some circumstances does this engagement lead to tolerance, while in others it produces B cell activation and secretion of immunoglobulins. Several mechanisms occur naturally in vivo abrogating the expression of deleterious autoantibodies and contributing to the state of self tolerance. In this review, we will examine different ways in which B cell tolerance can be broken, focusing on evidence showing that activated-T cells and/or their lymphokines can prevent B cell clonal deletion and thus have a potential role in the pathogenesis of autoimmune diseases. This approach is based on the well-known association of several lymphokines, such as IL-1, IL-2, IL-4, IL-5, and type I interferons, with autoimmune phenomena in vivo. PMID- 1627791 TI - Diagnosis of thalassemia using cDNA amplification of circulating erythroid cell mRNA with the polymerase chain reaction. PMID- 1627792 TI - Growth factors affecting human thrombocytopoiesis: potential agents for the treatment of thrombocytopenia. PMID- 1627793 TI - Mutations of the red blood cell membrane proteins: from clinical evaluation to detection of the underlying genetic defect. PMID- 1627794 TI - High levels of human glucocerebrosidase activity in macrophages of long-term reconstituted mice after retroviral infection of hematopoietic stem cells. AB - Gaucher disease is a leading candidate for somatic gene therapy using bone marrow (BM) cells as target tissue. Towards this end, we have constructed a retroviral vector (LG) in which the human glucocerebrosidase (GC) cDNA is driven by the Moloney murine leukemia virus (MoMLV) long terminal repeat (LTR). Day 12 to 14 colony-forming unit-spleen progenitor cells were infected by the LG virus with a 100% efficiency, and GC messenger RNA (mRNA) and protein were detected in the progeny of these cells. Tissues from long-term reconstituted mice analyzed 8 months posttransplantation with LG-infected BM contained the intact provirus at greater than 1 copy per cell, indicating effective infection of hematopoietic stem cells. Human GC mRNA generated by the viral LTR was detected in macrophages as well as other hematopoietic cells. Enzyme activity was increased fivefold and twofold in macrophages from BM and spleen, respectively, and could be precipitated with an antibody specific for human GC. Immunohistochemical analysis detected the human GC protein in 81% of the macrophages from five recipient mice. These data indicate that, after transduction of hematopoietic stem cells, the LG vector is capable of directing expression of human GC in the majority of macrophages from long-term reconstituted mice and producing enzyme levels comparable with endogenous mouse activity, suggesting that this virus may be useful in the treatment of Gaucher disease. PMID- 1627795 TI - Morphology in patients with severe aplastic anemia treated with antilymphocyte globulin. AB - One hundred and seventeen patients with severe aplastic anemia (SAA) were treated at our institution between 1976 and 1990 with antilymphocyte globulin (ALG) therapy. Seventy-nine (68%) are alive and probability of survival at 14 years, according to Kaplan and Meier, is 62% +/- 12%. Twenty-six patients developed a late clonal complication: 11 had a myelodysplastic syndrome (MDS) and 17 had paroxysmal nocturnal hemoglobinuria (PNH); two patients had both. The cumulative risk at 10 years is 42%. The development of MDS/PNH after SAA directly affects survival. The probability of being alive at 14 years is 81% +/- 10% for patients with stable disease and 36% +/- 13% for those with clonal evolution (P = .001). To look for predictive signs, we reevaluated peripheral blood and bone marrow cytomorphology at presentation, during regeneration, and in remission. We examined the peripheral blood values for hemoglobin, reticulocytes, granulocytes, thrombocytes, mean corpuscular volume (MCV), and fetal hemoglobin, as well as bone marrow for cellularity, erythropoiesis, myelopoiesis, and megakaryopoiesis. ALG therapy induces slow and incomplete recovery. Although in "remission," ALG patients have lower hemoglobin values, higher reticulocyte counts, lower granulocyte and platelet values, and a higher MCV and fetal hemoglobin than normal controls. They retain a reduced number of megakaryocytes and a persistence of atypical monocytes in bone marrow morphology as stigmata of their disease. Patients with late clonal complications show distinct morphologic abnormalities: patients with PNH have higher MCVs, higher granulocyte and reticulocyte counts, and more dyserythropoiesis at diagnosis and a lower hemoglobin with an increased proportion of erythroblasts in the bone marrow in "remission." Patients who later developed MDS are not different from the total patient population at diagnosis. After therapy, these patients are characterized by the presence of ring sideroblasts and atypical monocytes during regeneration and by a persistent increase in MCV, a higher fetal hemoglobin, lower granulocyte values, and megakaryocytic dysplasia during "remission." Thus, routine morphologic follow-up examination of blood and bone marrow can discover patients at risk for late hematologic complications after ALG therapy. PMID- 1627796 TI - Evidence that interleukin-6 does not play a role in the stimulation of platelet production after induction of acute thrombocytopenia. AB - The induction of thrombocytopenia results in elevated levels of thrombopoietin (TPO), which can be detected in the plasma of experimental animals. Acute, severe thrombocytopenia (platelet count less than 5% of control) was produced in mice by the administration of either guinea pig or rabbit antimouse platelet antiserum. Control mice received equal volumes of normal serum. At various times after the induction of thrombocytopenia (0.5, 1, 2, 3, 4, 6, 12, and 24 hours) citrated plasma was collected, and circulating interleukin-6 (IL-6) levels were measured using the IL-6-dependent murine hybridoma cell line B9. At no time points after induction of thrombocytopenia were plasma IL-6 levels significantly different from control animals that received normal serum. However, injection of heterologous serum did result in slightly elevated plasma IL-6 levels (at 2 and 3 hours) compared with basal levels measured in uninjected animals. This brief increase was not related to the production of thrombocytopenia. Protein fractions from the plasma of thrombocytopenic rabbits were also tested for the presence of IL-6. Preparations that contained TPO, as shown by stimulation of megakaryocyte maturation in vitro, did not contain detectable levels of IL-6. The ability of the B9 assay to detect the elevation of IL-6 levels in murine or rabbit plasma was verified after the administration of bacterial endotoxin, which is known to increase circulating IL-6 concentrations. IL-6 levels were highly elevated in rabbit or mouse serum after the administration of 5 mg/kg or 1 mg/kg of endotoxin, respectively. Anti-IL-6 antiserum did not neutralize the in vitro megakaryocyte maturation activity of partially purified TPO from the plasma of thrombocytopenic rabbits. In addition, IgG purified from the same antiserum did not neutralize partially purified TPO, as shown after incubation with TPO and subsequent precipitation with agarose-bound protein A. These results show that, unlike TPO, levels of IL-6 do not increase after the induction of acute, severe thrombocytopenia, and strongly suggest that IL-6 does not mediate the thrombopoietic response to acute thrombocytopenia. Although prolonged administration of IL-6 has been shown to induce thrombocytosis, IL-6 and TPO are apparently different and immunologically distinct molecules. PMID- 1627797 TI - Large, chronic doses of erythropoietin cause thrombocytopenia in mice. AB - Both large, acute doses of erythropoietin (EPO) and short-term hypoxia increase platelet counts in mice, but long-term hypoxia causes thrombocytopenia. Therefore, we tested the hypothesis that EPO injected in large, chronic doses (a total of 80 U of EPO over a 7-day period) might cause thrombocytopenia. EPO caused increased red blood cell (RBC) production, ie, increased hematocrits, RBC counts, mean cell volume (MCV), and reticulocyte counts (from P less than .05 to P less than .0005), and decreased thrombocytopoiesis, ie, decreased platelet counts, percent 35S incorporation into platelets, and total circulating platelet counts (TCPC) (P less than .0005). Femoral marrow megakaryocyte size was unchanged, but megakaryocyte number was significantly (P less than .005) reduced in mice treated with EPO. EPO-injected mice had increased spleen volumes (P less than .0005), but blood volumes (BV) were unchanged. In EPO-treated, splenectomized mice, RBC production was also increased (P less than .05 to P less than .0005) and platelet counts, TCPC, and percent 35S incorporation into platelets were decreased (P less than .05), but BV was not altered. Therefore, the decrease in platelet counts observed in EPO-treated mice was not due to increased BV or to an enlarged spleen. In other experiments, mice were rendered acutely thrombocytopenic to increase thrombocytopoiesis, and platelet and RBC production rates were determined. In mice with elevated thrombocytopoiesis, RBC counts, hematocrits, percent 59Fe RBC incorporation values, and MCV were decreased (P less than .05 to P less than .0005). Because 59Fe RBC incorporation and MCV were not elevated, the decrease in RBC counts and hematocrits does not appear to be due to bleeding. Therefore, we show that large, chronic doses of EPO increase erythropoiesis and decrease thrombocytopoiesis. Conversely, acute thrombocytopenia causes increased thrombocytopoiesis and decreased erythropoiesis. These findings support the hypothesis of competition between precursor cells of the erythrocytic and megakaryocytic cell lines (stem-cell competition) as the cause of thrombocytopenia in EPO-treated mice and the cause of anemia in mice whose platelet production rates were increased. PMID- 1627798 TI - Effects of synergistic cytokine combinations, low oxygen, and irradiated stroma on the expansion of human cord blood progenitors. AB - Expansion of hematopoietic progenitor cells in the mononuclear cell (MNC) fraction of human cord blood was evaluated under atmospheres containing reduced (5%) and normal (20%) oxygen tensions. Cells were cultured with synergistic cytokine combinations in suspension (without stroma) and on irradiated bone marrow stroma. Addition of interleukin (IL)-3 and IL-6 (IL-3/IL-6) provided a greater expansion of both total and progenitor cells than IL-1 and IL-3 (IL-1/IL 3). IL-3/IL-6 maintained a higher level of progenitors throughout the 8-week culture period, whereas progenitors disappeared earlier from cultures with IL 1/IL-3. This indicates that an earlier cell type was affected by IL-3/IL-6, and/or that IL-3/IL-6 favored self-renewal while IL-1/IL-3 induced differentiation. Reduced oxygen tension enhanced the productivity of these long term hematopoietic cultures (LTHC) under all conditions tested. In suspension cultures, reduced oxygen increased cumulative total cell production by 125% and 167%, and cumulative progenitor production by 68% and 21%, with IL-1/IL-3 and IL 3/IL-6, respectively. The presence of irradiated stroma increased cumulative progenitor cell production almost threefold in cultures without cytokines. In cultures with cytokines, the beneficial effect of stroma was less significant, but was greater under 20% O2 than 5% O2. Cultures under 5% O2 provided more progenitors and often maintained progenitors for 1 to 2 weeks longer than those under 20% O2. To quantitate more precisely the shift in cell populations induced by IL-3/IL-6 and stroma in cultures under 5% O2, flow cytometry analysis was used. By week 3, the addition of IL-3/IL-6 stimulated a 15-fold and 25-fold expansion of promyelocytes (CD15+CD11b-) in suspension and stromal cultures, respectively. Addition of IL-3/IL-6 also increased mature granulocyte (CD15hiCD11b+) and monocyte (CD15loCD11b+) numbers, while no effect was seen on T (CD3+) or B- (CD19+) lymphocytes. Endogenous production of IL-6 was significantly higher under 5% O2 in both suspension and stromal cultures, and IL-6 production was increased threefold by the addition of IL-1/IL-3. Very little IL-1 beta was produced in these cultures, and endogenous IL-3 and tumor necrosis factor (TNF) alpha were undetectable by enzyme-linked immunosorbent assay (ELISA) analysis. PMID- 1627799 TI - Erythropoietin-induced stimulation of differentiation and proliferation in J2E cells is not mimicked by chemical induction. AB - The J2E cell line is a novel erythroid cell line that differentiates in response to erythropoietin (Epo), the physiologic stimulus for erythropoiesis. After exposure to Epo, the cells synthesize hemoglobin, and we show here that this process is tightly linked to increases in cellular proliferation and DNA synthesis. The hormone-induced terminal differentiation also results in morphologic alterations and the accumulation of transcripts for alpha, beta maj, and beta min globins. c-myc messenger RNA levels increase rapidly after exposure to Epo and precede the increase in cell division, while c-myb undergoes a transient decrease. Differentiation of J2E cells can also be achieved with sodium butyrate, but, in contrast with Epo, this is associated with a retardation of replication and a sudden decrease in c-myc levels. These results show that, in this system, chemically induced differentiation differs from terminal maturation promoted by Epo and that the processes of proliferation and differentiation in J2E cells can be uncoupled. PMID- 1627800 TI - Thrombocytopoiesis in normal and sublethally irradiated dogs: response to human interleukin-6. AB - The response of megakaryocytes and platelets to the administration of recombinant human interleukin-6 (IL-6) was investigated in normal and sublethally irradiated dogs. IL-6 was administered for 2 weeks at doses of 10 to 160 micrograms/kg/d to normal animals to assess dose-response and toxicity. Subsequently, 40, 80, or 160 micrograms/kg/d for 2 weeks was administered to animals treated with 200 cG total body irradiation. Analysis of normal dogs showed a significant increment in the platelet count detectable approximately 11 days after initiation of IL-6 at all administered doses. Large platelets greater than 6.3 microns in diameter were observed 1 day after beginning IL-6, progressively increasing to as many as 19.1% of the total circulating platelets by day 10. The ploidy distribution of the marrow megakaryocytes did not differ from the normal at doses of less than or equal to 80 micrograms/kg/d, but at 160 micrograms/kg/d, a shift toward higher ploidy cells was noted. No change in total white count was noted; however, a decrease in hematocrit was seen at all doses. In the irradiated animals, the platelet count recovered earlier in the IL-6-treated dogs than in the controls, but no consistent change in the ploidy distribution was observed irrespective of dose. Large platelets were also noted in the treated animals, comprising up to 6.9% of the total platelet count. Fibrinogen levels were elevated to greater than 4 times normal. A significant decrease in hematocrit was seen in all animals, while no consistent change was noted in the white count. Elevations in serum cholesterol, triglycerides, and alkaline phosphatase, together with a decline in serum albumin were observed in all the treated animals (both normal and irradiated), but clinical symptoms were observed only in the dogs receiving greater than or equal to 80 micrograms/kg/d. The data show that IL-6 alone is capable of enhancing platelet recovery in dogs with bone marrow suppression. PMID- 1627801 TI - Human endothelial cells express integrin receptors on the luminal aspect of their membrane. AB - Endothelial cells (EC) form a dynamic interface between blood and the rest of the body. EC surface properties promoting adhesion of reactive plasma proteins and/or circulating cells might be of pivotal importance for the homeostasis of blood and tissues. EC express multiple integrin receptors that promote their attachment to the subendothelial matrix proteins. Among these receptors, alpha v beta 3 is of particular relevance on EC, since it is abundantly expressed and can bind many different matrix and plasma proteins. It is still unknown whether integrin receptors are selectively located to the basal side of EC membrane or may also be exposed on the cell surface in contact with blood. This issue was addressed using different experimental approaches. First, selective surface radioiodination using lactoperoxidase (LPO)-latex beads and immunoprecipitation analysis were performed. We found that cultured EC, similarly to human skin fibroblasts (HSF), expose alpha v beta 3 on both their apical (free) and basal (substratum-attached) surfaces. This held also for other integrins such as alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, and alpha 6 beta 1. Immunoprecipitation data were verified by morphological techniques. Immunofluorescence and immunogold-staining of EC with alpha v beta 3, as well as with beta 1 subfamily antibodies, showed a diffuse and granular distribution of these integrins on EC surface. alpha v beta 3 and beta 1 integrins were also detected on the apical membrane of EC at higher magnification by scanning electron microscopy (SEM). Finally, data obtained on cultured EC were confirmed in vivo on immunogold-labeled ultrathin cryosections of human vessels by transmission electron microscopy (TEM). Data indicate, that in addition to their role in promoting EC attachment to extracellular matrix proteins, integrin receptors of EC can be exposed to blood-stream and eventually be available for binding of plasma proteins and circulating cells. PMID- 1627802 TI - Transcellular metabolism of arachidonic acid: increased platelet thromboxane generation in the presence of activated polymorphonuclear leukocytes. AB - Human polymorphonuclear leukocytes (PMN) activated by n-formyl-methionyl-leucyl phenylalanine (fMLP), in the presence of cytochalasin B, are able to induce activation of coincubated autologous platelets "via" cathepsin G released from the azurophilic granules. However, thromboxane (Tx) B2 production in this system cannot be completely explained by cathepsin G-stimulated platelet arachidonate metabolism. Indeed, the amount of TxB2 found in supernatants of platelet/PMN suspensions challenged with 1 mumol/L fMLP was twofold to fourfold higher than that measured when platelets were stimulated by supernatants from fMLP-activated PMN. In the present report, we analyzed the possibility that PMN-induced TxB2 production in this system is the result of transcellular metabolism of arachidonic acid (AA) between fMLP-activated PMN and cathepsin G-stimulated platelets. 3H-AA-labeled PMN were used to test if a transfer of AA or metabolite(s) occur from PMN to platelets. Our results showed that: (1) 3H-TxB2 and 3H-12-HHT are synthesized when 3H-AA-labeled PMN are activated mixed to unlabeled platelets; (2) total radioactivity released by fMLP-stimulated PMN is increased in the presence of platelets, whereas the membrane content of unesterified 3H-AA is reduced; (3) platelet cyclooxygenase inhibition completely prevents 3H-TxB2 synthesis; and (4) inhibition of cathepsin G-induced platelet activation with the antiprotease eglin C blocks the formation of 3H-TxB2. These data show that in the experimental system used, platelets use PMN-derived unmetabolized AA to synthesize TxB2. PMID- 1627803 TI - Regulatory effects of gallium on transferrin-independent iron uptake by human leukemic HL60 cells. AB - Gallium, a pharmacologically important metal, resembles iron with respect to transferrin (Tf) binding and Tf receptor-mediated cellular uptake. In the present study, we examined the effect of gallium on Tf-independent iron uptake by HL60 cells. In contrast to the inhibitory effect of Tf-gallium on Tf-iron uptake, gallium nitrate, in a time-, temperature-, and concentration-dependent manner, stimulated Tf-independent uptake of iron-nitrilotriacetic acid (Fe-NTA). Preexposure of cells to gallium followed by removal of gallium also resulted in sustained stimulation of iron uptake. The anti-Tf receptor monoclonal antibody 42/6 blocked Tf-iron uptake, but had no effect on gallium-induced stimulation of Tf-independent iron uptake. Gallium increased the number of cell membrane iron binding sites, without a change in their affinity for iron. Ferric chloride stimulated Tf-independent gallium uptake. Although gallium nitrate inhibited cell growth in Tf-free medium, cellular proliferation was restored by Fe-NTA. Gallium and iron appear to share the same Tf-independent cellular uptake system in HL60 cells. Exposure of cells to gallium results in the activation of cell membrane non-Tf iron carriers that may play a role in overcoming the Tf-independent growth inhibitory effects of gallium. PMID- 1627804 TI - Human embryonic zeta-globin chain expression in deletional alpha-thalassemias. AB - zeta-Globin chain expression in carriers of a number of deletional alpha thalassemias is investigated by radioimmunoassay. In a few cases, zeta-globin mRNAs are also studied. zeta-Globin chains are detected in (--SEA/), (--MED/), and (--SPAN/) deletions, but not in six other deletional mutations. These results suggest that the DNA element capable of suppressing zeta-globin expression in adult erythroid cells is present within the (--SPAN/) deletion, while the DNA fragment between the 5' breakpoints of the (--SA/) and the (--SEA/) deletions may contain sequences necessary for augmenting zeta-globin expression in adult erythroid cells. Furthermore, zeta-globin chains are shown by an immunocytologic technique to be present in all circulating erythrocytes in carriers of the (- SEA/) and (--MED/) deletions. This simple immunocytologic test is highly sensitive and specific to detect adult carriers of either the (--SEA/) or (- MED/) deletions, and can be used for the detection of couples at risk of pregnancies involving fetuses with homozygous alpha-thalassemia. PMID- 1627805 TI - The low risk of hepatitis C virus transmission among sexual partners of hepatitis C-infected hemophilic males: an international, multicenter study. AB - To study the transmission rate of hepatitis C virus (HCV) in the female sexual partners of antibody-positive hemophilic males, 106 partners from three hemophilia centers located in Europe, America, and Australia were tested for HCV seropositivity using a first-generation enzyme-linked immunosorbent assay (ELISA 1) and, subsequently, a second-generation ELISA (ELISA-2) and a supplemental recombinant immunoblot assay. Additionally, the cohort was tested for the presence of antibody to the human immunodeficiency virus type-1 and hepatitis B virus markers. No female partner was HCV antibody-positive using the ELISA-1 test, whereas five were seropositive by the ELISA-2 test. Three of these five female partners were seropositive on the supplemental test, the remaining two having indeterminate results, for an overall prevalence of 2.7%. Thus, even with the use of sensitive testing, the prevalence of HCV infection remains low in this cohort, showing that the efficiency of heterosexual transmission of HCV is poor. PMID- 1627806 TI - Failure to detect evidence of human T-lymphotropic virus (HTLV) type I and type II in blood donors with isolated gag antibodies to HTLV-I/II. AB - Of the 267,650 blood donations from members of the US armed forces, 72 (0.027%) were serologically confirmed to be positive for human T-lymphotropic virus type I/II (HTLVpos) and 379 (0.14%) were Western blot (WB)-indeterminate with banding pattern restricted to the proteins encoded by the gag gene only (HTLVind). To determine whether these apparently healthy HTLVind blood donors are infected with HTLV-I or HTLV-II, coded specimens from randomly selected military blood donors (n = 73) were tested for antibodies to HTLV by WB and radioimmunoprecipitation assay (RIPA) using HTLV-I (MT-2) antigens, by enzyme immunoassay using synthetic peptides representing the immunodominant epitopes of HTLV, and for sequences of proviral HTLV DNA by the polymerase chain reaction (PCR). Of the 73 HTLVind donors, none showed presence of env reactivity by HTLV WB and RIPA. Minimal reactivity was observed with synthetic immunodominant motifs derived from the env protein of HTLV-I (Env-1(191-214) and Env-5(242-257)) or HTLV-II (Env-2(187-209) and Env-20(85-102)) and gag protein (Gag-1a(102-117) and Gag-10(364-385)). A peptide corresponding to the endogenous retroviral sequence with structural homologies to the gag protein of HTLVs (RTVLgag) reacted with antibodies not only in HTLVpos (88%) and HTLVind (42% to 66%) specimens, but also reacted with normal control subjects (60%). Furthermore, none of the 73 HTLVind specimens demonstrated presence of the HTLV genome when amplified with primers for the pol and tax/rex region. Six to 23 months from the initial test, 27 subjects still gave indeterminate WB patterns, and 13 of these repeat specimens were still negative for the presence of HTLV genome. We conclude that individuals at low risk for HTLV infection who have HTLVind WB reactivity are rarely, if ever, infected with HTLV-I or HTLV-II. PMID- 1627807 TI - Detection of circulating donor white blood cells in patients receiving multiple transfusions. AB - Significant morbidities are associated with the routine administration of blood products. Although the exact etiology of these complications may be unknown, many are thought to arise from the incidental cotransfusion of "donor" lymphocytes. We have developed an assay to detect small numbers of male white blood cells (WBCs) circulating in female patients who have received multiple blood transfusions using the polymerase chain reaction (PCR). Twenty female patients undergoing major surgical procedures were studied and received an average of 9.3 U of packed red blood cells (4.8 U from male donors) and 11.7 U of platelets (6.1 U from male donors). DNA was extracted from whole blood or peripheral blood buffy coats posttransfusion and PCR performed using oligonucleotides designed to amplify a segment within the repetitive Y-chromosome DYZ1 locus. Posttransfusion, 15 of 20 women showed evidence of circulating male WBCs for an average of 2.0 days (range, 1 to 6). We conclude that (1) DYZ1 PCR analysis is a useful approach for the detection of small numbers of circulating transfused male WBCs in female patients; and (2) circulating donor WBCs persist for a mean of 2.0 days in the majority of women receiving multiple transfusions. Future application of this technique may detect persisting or proliferating WBCs and lead to an improved understanding of common transfusion-related morbidities. PMID- 1627808 TI - MDR1 RNA expression is an independent prognostic factor in acute myeloid leukemia. PMID- 1627809 TI - Differential expression of cytokines in human blood monocyte subpopulations. PMID- 1627810 TI - Long-term follow-up of a controlled trial comparing a combination of methotrexate plus cyclosporine with cyclosporine alone for prophylaxis of graft-versus-host disease in patients administered HLA-identical marrow grafts for leukemia. PMID- 1627811 TI - Inadequate monitoring of warfarin dosage. PMID- 1627812 TI - Recertification in hematology. Hematology Board of the American Board of Internal Medicine. PMID- 1627813 TI - Prognostic factors and natural history in lymph node-negative breast cancer patients. AB - The prognostic significance of clinical and histological factors as well as hormone receptors was analyzed in a population of 3,064 lymph node-negative breast cancer patients operated in the Stockholm region between 1976 and 1988. None of these patients received systemic adjuvant treatment. Multivariate analysis showed that only histological tumor size, number of examined axillary lymph nodes, and progesterone receptors were independent prognostic factors in terms of recurrence-free interval. An individual risk of recurrence was calculated taking into account these three factors to discriminate between three groups of patients with a risk of less than 15%, 15-25%, and more than 25% of recurrence at 5 years. Similar results were obtained taking into account only the first two factors. The prognostic information added by the knowledge of progesterone receptors only changed the recurrence rate in approximately 3%. This study showed that conventional prognostic factors permit the identification of high risk lymph node-negative breast cancer patients. Results obtained by the use of new more sophisticated factors should be compared with those obtained analyzing strong conventional prognostic factors. PMID- 1627814 TI - pS2 expression in primary breast carcinomas: relationship to clinical and histological features and survival. AB - pS2 protein expression has been reported to have prognostic significance in human breast carcinomas and to correlate with estrogen receptor positivity, although these findings have not been confirmed by all investigators. pS2 positivity was compared to various clinical and histologic parameters in a retrospective study of 290 patients (median follow-up 7.2 years) and significantly correlated with tumor grade and estrogen receptor content (p = 0.001 and p = 0.0007, respectively). Significant associations between pS2 positivity and lymph node metastases, T stage, histologic tumor type, and patient age were not observed. Univariate and multivariate analyses (controlling for estrogen receptor content, T and N stage) of the patient population at large showed that pS2 positivity was not predictive of disease-free or overall survival. Univariate analysis of lymph node negative patients demonstrated that both pS2 and estrogen receptor positivity were significantly associated with a better outcome. Multivariate analysis of these patients, however, showed that only estrogen receptor data had independent prognostic significance. This study suggests that immunohistochemical analysis for pS2 protein expression will not contribute additional prognostic information if the estrogen receptor content is known. PMID- 1627815 TI - Prognostic factors in node-positive operable breast cancer patients receiving adjuvant chemotherapy. AB - A retrospective analysis of prognostic factors in 214 consecutive node-positive (N+) operable breast cancer patients, receiving Melphalan + 5-fluorouracil adjuvant chemotherapy between 1980 and 1984 was performed. Median follow-up was 95 months. Actuarial disease-free interval (DFI) and survival (S) were determined according to age, menopausal status, histology, size of primary tumor (T), multifocality, tumor location, hormonal receptor status, number of N+, size of N+, tumor spread in axillary fat, and interval between surgery and onset of adjuvant chemotherapy. On univariate analysis two factors were prognostic for DFI and S: number of N+ and T size. A comparison between traditionally classified T1 and T2 patients revealed no significant difference, but when the cut-off point was shifted from 2 cm to 3 cm, T size represented a highly significant prognostic factor. In patients with T less than or equal to 3 cm 5-year DFI was 54% and 5 year S was 76%, while in patients with T greater than 3 cm the respective values were 23% (p less than 0.001) and 41% (p less than 0.001). These significant DFI and S differences persisted after adjustment for number of N+ by bivariate analysis. Multivariate analysis supported the importance of T greater than 3 cm as a strong adverse predictor. Four adverse variables, T greater than 3 cm, number of N+ greater than or equal to 4, multifocality, and tumor spread in axillary fat were used to divide our patients into three subsets with significantly different DFI: Group I, with none of the above factors; Group II, with only one factor present; and Group III, with more than one factor present (5 years DFI 66%, 45%, and 21%, respectively; p less than 0.001). PMID- 1627816 TI - Weekly low-dose mitoxantrone plus doxorubicin as second-line chemotherapy for advanced breast cancer. AB - Weekly low dose mitoxantrone (3 mg/m2) plus doxorubicin (8 mg/m2) was administered as second-line chemotherapy to 33 patients with advanced breast cancer. Four out of 28 evaluable patients (14%) obtained a partial response with a median duration of 34 weeks (range 18-67+ weeks), while 8 patients (29%) showed stable disease with a median duration of 28 weeks (range 11+-60 weeks). Gastrointestinal toxicity and alopecia were mild. Grade II and III leukopenia occurred in 63% of the courses without serious infectious disease. Four patients experienced an asymptomatic drop of 16-20% in the left ventricular ejection fraction (LVEF) after relatively low cumulative doses of each drug, and one patient with a history of pericarditis carcinomatosa and mediastinal irradiation developed a heart failure. In conclusion, this second-line combination treatment had moderate activity in breast cancer and caused only few subjective side effects, especially with respect to gastrointestinal symptoms. PMID- 1627817 TI - Comparison of pain, motion, and edema after modified radical mastectomy vs. local excision with axillary dissection and radiation. AB - Recent data suggest that prognosis is similar for women with primary breast cancer whether they receive modified radical mastectomy (MRM) or local excision and axillary dissection with radiation (XRT). The effects of either of these treatments on arm mobility, pain, or edema have not been compared. To assess the impact of MRM or XRT on mobility, pain, or edema, we evaluated patients treated in a prospective randomized trial designed to assess prognosis following MRM or XRT. All were provided a standardized physical therapy program including arm mobilization, shoulder strengthening, prevention and treatment of upper extremity edema, and education about arm function. Patients were evaluated for chest wall pain, arm motion, muscle strength, and edema as determined by circumferential measurements at the wrist, forearm, and arm. Evaluations were performed preoperatively and at yearly anniversaries of their surgery. Women receiving XRT had more chest wall tenderness at 1 and 2 years after surgery than those receiving MRM (p2 less than 0.0001 and p2 = 0.0007 respectively). Those receiving MRM were slower to reach their preoperative range of motion (ROM) (p2 = 0.043). Incidence of muscle weakness was similar in both groups. The few patients with local recurrence of tumor had more upper extremity edema than those who did not recur (p2 = 0.085) at 1 year and (p2 = 0.02) at 2 years. In patients who did not develop local recurrence, those who had received XRT had greater but nonsignificant increases in upper extremity circumferential measures compared with those receiving MRM at any anniversary evaluation. Patients receiving MRM and XRT are likely to have some differences in functional outcome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627819 TI - Dental students go on strike. PMID- 1627818 TI - Human gene therapy: present and future. AB - The hematopoietic system and the liver are two primary target organs for attempting somatic gene therapy of hereditary deficiencies. Several leading laboratories have recently been able to demonstrate that bone marrow cells from rodents and non-human primates can be successfully transduced with foreign genes, resulting in the functional expression of these genes in culture. The genetically reconstituted cells can subsequently be transplanted into X-irradiated recipients, and expression of the transduced genes is observed in the recipients for more than 6 months. Subsequently, gene transfer into peripheral T-lymphocytes in humans has been attempted, and the clinical trials are currently in progress. The liver is the other major organ under intensive investigation. Primary hepatocytes can be isolated from rodents, rabbits, and dogs, and successfully transduced with recombinant retroviruses. After autologous transplantation, long term survival of the engrafted cells in vivo has been observed. More recently, it has been shown that human hepatocytes can also be efficiently transduced with recombinant retroviruses. These experimental results have laid the foundation for somatic gene therapy of hereditary deficiencies in humans in the future. PMID- 1627820 TI - Denturists legalized in The Netherlands. AB - In 1990 the Dutch Government accepted A law which made it possible for dental prosthetic technicians to manufacture full dentures on patients. The Dutch Dental Association opposed of this law. The authors explain, why this law was accepted and the experience with this law so far. PMID- 1627822 TI - Bad management, bad business. AB - The past ten years the market for dentists in Denmark has been shrinking. This is having an effect on the financial position of dental practices. It is more difficult for dentists to maintain a certain income level. Several problems are analysed and possible solutions are being discussed. PMID- 1627821 TI - Dentistry for children. How it is done in British Columbia, Canada. A report of an exchange-student from Germany. AB - In Vancouver, there is a Children's Hospital unique for its kind: Various paediatric departments are covered under one roof. Matthias Hammer, a dental student from Germany, describes their cooperation and the import of the dental department. PMID- 1627823 TI - Coming to Finland. The Dental School of Kuopio. AB - The Faculty of Dentistry at the University of Kuopio became the first dental school in Finland and its first dean was Heikki Luoma. Today, next to the undergraduate education, there is a post graduate training-program as well as scientific research to achieve the degree of Doctor of Dental Science. PMID- 1627824 TI - Selectivity in storage hexamerin clearing demonstrated with hemolymph transfusions between Hyalophora cecropia and Actias luna. AB - When Hyalophora cecropia hemolymph was injected into wandering Actias luna larvae, a methionine-rich hexamerin was selectively transferred to the host's fat body, and completely cleared from the hemolymph by the time of pupal eclosion. Donor arylphorin was 30-40% removed from the hemolymph, and riboflavin-binding hexamerin was even less completely cleared. During the pupal-adult molt, these rates were reversed: methionine-rich hexamerin disappeared no faster than bovine serum albumin, while riboflavin-binding hexamerin was rapidly and completely cleared from the hemolymph, even though A. luna hemolymph lacks a homologue of this protein; arylphorin, again, was cleared at an intermediate rate. Selective clearing of the three hexamerins occurred at similar stages in H. cecropia, their species of origin. Developmentally programmed clearing, with selectivity at least partially conserved between genera, was also demonstrated with transfused vitellogenin: in A. luna females that were forming yolk, H. cecropia vitellogenin was cleared more rapidly than bovine serum albumin; but in younger females, and in males at all stages of metamorphosis, this Mr 510,000 molecule was instead an indicator of nonselective, large protein clearing. Nonselective clearing was more complete during adult development than during pupation. It also showed signs of being more effective for small than for large proteins, insensitive to carbohydrate conjugates, and unsaturated at the protein levels used. PMID- 1627825 TI - Carbamoyl phosphate synthetase (CPSase) in the PYR1-3 multigene of Dictyostelium discoideum. AB - We have isolated and sequenced the genomic DNA from the slime-mould Dictyostelium discoideum multi-gene (PYR1-3) encoding the carbamoyl phosphate synthetase II domain (CPSase, EC.6.3.5.5). We describe sequencing by oligo-walking directly on PCR product in the solid-phase, avoiding subcloning procedures. The 2.4 kb fragment completes the sequence of the PYR1-3 gene, has no introns, and has the same structure as the rudimentary gene of Drosophila melanogaster. Comparison with the carbamoyl phosphate synthetases (CPSase I and CPSase II) of other species supports the hypothesis that this gene has arisen by tandem duplication from a smaller common ancestral gene in the progenote. PMID- 1627826 TI - Sequence analysis of the large and small subunits of human ribonucleotide reductase. AB - We have isolated and sequenced overlapping cDNA clones from a breast carcinoma cDNA library containing the entire coding region of both the R1 and R2 subunits of the human ribonucleotide reductase gene. The coding region of the human R1 subunit comprises 2376 nucleotides and predicts a polypeptide of 792 amino acids (calculated molecular mass 90,081). The sequence of this subunit is almost identical to the equivalent mouse ribonucleotide reductase subunit with 97.7% homology between the mouse and human R1 subunit amino acid sequences. The coding region of the human R2 subunit of ribonucleotide reductase comprises 1170 nucleotides and predicts a polypeptide of 389 amino acids (calculated molecular mass 44,883), which is one amino acid shorter than the equivalent mouse subunit. The human and mouse R2 subunits display considerable homology in their carboxy terminal amino acid sequences, with 96.3% homology downstream of amino acid 68 of the human and mouse R2 proteins. However, the amino-terminal portions of these two proteins are more divergent in sequence, with only 69.2% homology in the first 68 amino acids. PMID- 1627827 TI - A C. elegans gene encodes a protein homologous to mammalian calreticulin. AB - The gene encoding a C. elegans homologue of the mammalian reticuloplasmin, calreticulin, was cloned and sequenced and the amino-acid sequence of its product deduced. The coding region of the gene comprises three exons separated by introns of 95 and 55 nucleotides, followed by either 158 or 279 bases of 3' non-coding sequence before putative polyadenylation signals. The precursor protein of 395 residues includes an N-terminal signal sequence of 13 residues. The C-terminus has the ER retention signal HDEL preceded by a polyacidic zone similar to known mammalian calreticulins. The sequence shows a 61% identity with mouse calreticulin, increasing to 82% in the proline-rich region of the molecule. Comparison of the C. elegans sequence with the calreticulin-related antigen RAL-1 of Oncocerca volvulus shows 73% identity, excluding the calreticulin C-terminal region. The sequence of this region differs markedly from RAL-1 where the parasite protein has a polybasic stretch and no ER retention signal. The C. elegans gene described here and designated crt-1 was mapped to a region towards the left-hand end of Chromosome V on the physical map of the genome. Southern blotting of genomic DNA indicates that in C. elegans the calreticulin homologue exists in only one form as the product of a single gene. PMID- 1627828 TI - The intronless mouse gene for the tissue specific splicing protein SmN is a processed pseudogene containing a stop codon after thirty-one amino acids. AB - The SmN protein is a component of small ribonucleoprotein particles which is closely related to the ubiquitously expressed splicing proteins SmB and B' but is expressed in only a small number of cells and tissues. We have isolated a mouse SmN-related sequence which lacks introns and contains multiple changes from the SmN cDNA sequence including a stop codon after thirty-one amino acids which would prevent it encoding functional SmN protein. This indicates that this intronless gene is a processed pseudogene and that the functional gene has yet to be isolated. In agreement with this southern blotting of mouse DNA with SmN probes reveals bands, additional to those derived from the pseudogene, which are characteristic of an intron-containing SmN gene. The relationship of the pseudogene to the functional SmN gene and to an intronless SmN-related sequence in the rat genome is discussed. PMID- 1627829 TI - Transcription on lampbrush chromosome loops in the absence of U2 snRNA. AB - The five small nuclear RNAs (snRNAs) involved in splicing occur on the loops of amphibian lampbrush chromosomes and in hundreds to thousands of extrachromosomal granules called B snurposomes. To assess the role of these snRNAs during transcription and to explore possible relationships between the loops and B snurposomes, we injected single-stranded antisense oligodeoxynucleotides (oligos) against U1 and U2 snRNA into toad and newt oocytes. As shown before, antisense U1 and U2 oligos caused truncation of U1 and complete destruction of U2 snRNAs, respectively. However, injection of any oligo, regardless of sequence, brought on dramatic cytological changes, including shortening of the chromosomes and retraction of the lateral loops, with concomitant shutdown of polymerase II transcription, as well as disappearance of some or all of the B snurposomes. When injected oocytes were incubated for 12 h or longer in physiological saline, these changes were reversible; that is, the chromosomes lengthened, transcription (detected by 3H-UTP incorporation) resumed on newly extended lateral loops, and B snurposomes reappeared. In situ hybridization showed that loops and B snurposomes had negligible amounts of U2 snRNA after recovery from injection of the anti-U2 oligo, whereas these structures had normal levels of U2 snRNA after recovery from a control oligo. Thus, the morphological integrity of B snurposomes and lampbrush chromosome loops is not dependent on the presence of U2 snRNA. Because transcription occurs in the absence of U2 snRNA, we conclude that splicing is not required for transcription on lampbrush chromosome loops. PMID- 1627830 TI - Two genes in Saccharomyces cerevisiae encode a membrane-bound form of casein kinase-1. AB - Two cDNAs encoding casein kinase-1 have been isolated from a yeast cDNA library and termed CKI1 and CKI2. Each clone encodes a protein of approximately 62,000 Da containing a highly conserved protein kinase domain surrounded by variable amino- and carboxy-terminal domains. The proteins also contain two conserved carboxy terminal cysteine residues that comprise a consensus sequence for prenylation. Consistent with this posttranslational modification, cell fractionation experiments demonstrate that intact CKI1 is found exclusively in yeast cell membranes. Gene disruption experiments reveal that, although neither of the two CKI genes is essential by itself, at least one CKI gene is required for yeast cell viability. Spores deficient in both CKI1 and CKI2 fail to grow and, therefore, either fail to germinate or arrest as small cells before bud emergence. These results suggest that casein kinase-1, which is distributed widely in nature, plays a pivotal role in eukaryotic cell regulation. PMID- 1627831 TI - Extracellular signal-regulated kinases 2 autophosphorylates on a subset of peptides phosphorylated in intact cells in response to insulin and nerve growth factor: analysis by peptide mapping. AB - The phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2) in response to insulin in Rat 1 HIRc B cells and in response to nerve growth factor (NGF) in PC12 cells has been examined. ERK1 and ERK2 are phosphorylated on serine in the absence of the stimuli and additionally on tyrosine and threonine residues after exposure to NGF and insulin. NGF stimulates tyrosine phosphorylation of ERK1 more rapidly than threonine phosphorylation. Two dimensional phosphopeptide maps of both ERK1 and ERK2 phosphorylated in intact cells treated with NGF or with insulin display the same three predominant phosphopeptides that comigrate when digests of ERK1 and ERK2 are mixed. As many as five additional phosphopeptides are detected under certain conditions. Autophosphorylated recombinant ERK2 also contains the three tryptic phosphopeptides found in ERKs labeled in intact cells. These experiments demonstrate that ERK1 and ERK2 are phosphorylated on related sites in response to two distinct extracellular signals. The data also support the possibility that autophosphorylation may be involved in the activation of the ERKs. PMID- 1627832 TI - Testing the in vivo role of protein kinase C and c-fos in neurite outgrowth by microinjection of antibodies into PC12 cells. AB - To define the molecular bases of growth factor-induced signal transduction pathways, antibodies known to block the activity of either protein kinase C (PKC) or the fos protein were introduced into PC12 cells by microinjection. The antibody against PKC significantly inhibited neurite outgrowth when scored 24 h after microinjection and exposure to nerve growth factor (NGF). Microinjection of antibodies to fos significantly increased the percentage of neurite-bearing cells after exposure to either NGF or basic fibroblast growth factor (bFGF) but inhibited the stimulation of DNA synthesis by serum, suggesting that in PC12 cells, fos is involved in cellular proliferation. Thus, activation of PKC is involved in the induction of neurite outgrowth by NGF, but expression of the fos protein, which is induced by both NGF and bFGF, is not necessary and inhibits neurite outgrowth. PMID- 1627835 TI - Communication--a theatre art. AB - The art of communication is not easy. We communicate with patients by speech, writing, illustrations, gesture, touch and smell, sometimes singly, sometimes all at the same time. The firmness of a handshake carries meaning as clearly as words, in the same way that a smile radiates confidence and friendliness. Good communication carries its own reward: the trust of a patient. PMID- 1627834 TI - Nerve growth factor employs multiple pathways to induce primary response genes in PC12 cells. AB - Nerve growth factor (NGF) leads to neuronal differentiation of PC12 cells and promotes their survival in serum-free medium. Past studies have shown that purine analogues block some of the effects of NGF but not others and thus that they can be used to dissect the mechanistic pathways of its action. In the present work we used 2-aminopurine (2-AP) and 6-thioguanine (6-TG) to examine whether NGF causes activation of primary response genes through a single signaling pathway or via multiple pathways. Northern blot analysis and nuclear run-off transcription assays were used to assess the activation of c-fos, c-jun, TIS1, TIS8, and TIS11 after exposure of PC12 cells to NGF in the presence or absence of 2-AP and 6-TG. Our findings indicate that NGF appears to employ at least three distinct pathways to induce early genes in PC12 cells. This suggests that the NGF signaling mechanism diverges at an early point after interaction of NGF with its receptor. PMID- 1627833 TI - Transmembrane-mediated changes in [Ca2+] are involved in the signaling pathway leading to macrophage cytocidal differentiation: implications of localized changes in intracellular [Ca2+] and of interferon priming on Ca2+ utilization. AB - Macrophage cytocidal activation requires the sequential impingement on the macrophage of a priming stimulus (interferon [IFN] alpha, beta, or gamma) and a triggering stimulus (such as polyinosinic acid:polycytidylic acid [poly [I:C]] or bacterial lipopolysaccharide). The mechanism of progression from the IFN-primed state to the cytocidal state is poorly understood. By quantifying the level of expression of a gene product (complement component factor B [Bf]) associated with cytocidal activation and through the use of phenotypically distinct populations of macrophages (unprimed and IFN-primed), we have investigated the functional necessity of changes in intracellular concentration of free calcium ions ([Ca2+]i) in signaling the transition from the primed to the cytocidal state. Elevating the [Ca2+]i by incubation of unprimed macrophages with the calcium ionophore, ionomycin, failed to induce the expression of Bf. By contrast, Bf was expressed at high levels when IFN-primed macrophages were exposed to ionomycin, suggesting that priming induced within the macrophages the capacity to respond to a nonspecific change in [Ca2+]i. Quantification of the [Ca2+]i in response to exposure to ionomycin revealed an initial transient elevation, followed by a secondary sustained component. No differences in these changes were observed between unprimed and IFN-primed macrophages. We therefore questioned if changes in [Ca2+]i were also implicated in the transition between the primed and the cytocidal state using the ligand, poly [I:C]. In contrast to ionomycin, incubation of IFN-primed macrophages with poly [I:C] did not sustain measurable increases in [Ca2+]i, yet fully stimulated the transition from the IFN primed to the cytocidal state. However, incubation of IFN-primed macrophages with poly [I:C] in the presence of 1) a Ca2+/ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid buffer calculated to clamp the extracellular concentration of free calcium ions to a value approximately equal to the resting [Ca2+]i; 2) the calcium channel blocker verapamil; or 3) the intracellular Ca2+ antagonists (W-7, W-13, and TMB-8) substantially inhibited the induction of Bf. Collectively, these data support the following conclusions. First, that changes in [Ca2+]i comprise an important element in the induction of progression from the IFN-primed to the cytocidal state. Second, the failure to detect global changes in [Ca2+]i in response to the ligand, poly [I:C], suggests that changes in [Ca2+]i or Ca2+ movement may occur in either a spatially restricted or in an asynchronous cyclical fashion and are not detected by population fluorescence measurements. Third, the source of the relevant Ca2+ is extracellular. Fourth, our findings suggest that priming influences macrophage functional responses at a locus that is distal to the changes in [Ca2+]i, thereby potentially allowing signaling processes to be utilized to initiate different cellular responses. PMID- 1627836 TI - The swab rack--an outdated ritual. AB - The risk of Theatre Staff becoming infected from blood borne viruses such as HIV and Hepatitis B is steadily increasing. Sir David Cox's report (1988) predicted that the number of people infected with HIV by the end of 1987 would be between 20,000 and 50,000. Although these predictions are now thought to be more accurately estimated between 12,000 and 26,000, the number of people developing Aids is still expected to rise at an alarming rate. The precautions taken within the Theatre Department to reduce this risk are becoming transparently inadequate. It is no longer sufficient--or acceptable practice--to only be vigilant in avoiding blood contamination if the patient falls within a certain 'high risk' category. A happily married, middle aged woman may also be a virus carrier, particularly considering the long dormancy the HIV virus can exhibit before being detectable. It must be assumed that everyone is a potential carrier and the same precautionary measures taken for every patient, regardless of their past history, or present appearance. PMID- 1627838 TI - Supporting cast. PMID- 1627837 TI - African diary. PMID- 1627839 TI - How nurses will maintain the quality of nursing care if the skill mix changes. PMID- 1627840 TI - Organ donation and the theatre nurse. PMID- 1627841 TI - Bone transplantation. AB - Organ transplantation is a recognised surgical procedure. Bone transplantation (allografting) is a procedure being used increasingly in Orthopaedic reconstructive surgery. It involves the transplantation of bone between two unrelated individuals. This technique started expanding in the 1970's in the US and Canada and is rapidly gaining popularity in the UK. No blood grouping or tissue typing is required and the recipient does not need immunosuppressive therapy. PMID- 1627842 TI - The homograft department. AB - Perfusionists are highly skilled professionals providing essential life support, enabling patients to undergo open heart surgery. Although this is the main function at the Royal Liverpool Children's Hospital, Alder Hey, they also manage a Homograft bank. Also known as a heart valve bank, this is a completely independent branch of the perfusion department. PMID- 1627843 TI - Student nurse's experience of theatre nursing. The influence of adult learning theory. PMID- 1627844 TI - Pre-operative teaching--a literature review. PMID- 1627845 TI - The nurse's progress. PMID- 1627846 TI - Developments in post-registration education and practice. PMID- 1627847 TI - The shadow of PK2. Justifying learner nurse allocation to the operating department. PMID- 1627848 TI - Are we meeting their needs. AB - The aim of this pilot study is to discover the student nurses' learning needs and perceptions during their operating department allocation and whether we are meeting those needs. Also, what influence their perceptions have had upon selecting perioperative nursing as a career. The study focuses upon semi structured interviews with student nurses and their accounts of their experiences of being learners in the operating department. During their allocation, students are able to view surgery and to assist in the recovery of patients and to understand what a surgical patient experiences. They are exposed to the roles and responsibilities of operating department nurses. However, little is known about how students perceive these experiences. In this study two groups of students from the same year were interviewed to determine their perceptions and needs during the allocation and whether their learning needs had been met. PMID- 1627849 TI - The Children Act 1989--a brief report. PMID- 1627850 TI - This was your life: how your skeleton may be coaxed out of the cupboard. PMID- 1627851 TI - A paediatric day service. PMID- 1627852 TI - Quality assurance in practice. PMID- 1627853 TI - Paediatric anaesthesia--Portugal. PMID- 1627854 TI - Wound dressings. PMID- 1627855 TI - 'Observations on temperature changes in patients undergoing insertion of a dynamic hip screw. PMID- 1627856 TI - The Confidential Report on Peri-operative Deaths. PMID- 1627857 TI - Children in theatre: meeting their needs. PMID- 1627858 TI - Natalie. A patient care study. PMID- 1627859 TI - Lipid-suppressed single- and multisection proton spectroscopic imaging of the human brain. AB - Spectroscopic images of the brain have great potential in disease diagnosis and treatment monitoring. Unfortunately, interfering lipid signals from subcutaneous fat and poor water suppression due to magnetic field inhomogeneities can make such images difficult to obtain. A pulse sequence that uses inversion recovery for lipid suppression and a spectral-spatial refocusing pulse for water suppression is introduced. In contrast to methods that eliminate fat signal by restricting the excited volume to lie completely within the brain, inversion recovery techniques allow imaging of an entire section without such restrictions. In addition, the spectral-spatial pulse was designed to provide water suppression insensitive to a reasonable range of B0 and B1 inhomogeneities. Several data processing algorithms have also been developed and used in conjunction with the new pulse sequence to produce metabolite maps covering large volumes of the human brain. Images from single- and multisection studies demonstrate the performance of these techniques. PMID- 1627860 TI - Proton MR spectroscopy of gadolinium-enhanced multiple sclerosis plaques. AB - Magnetic resonance (MR) imaging and proton MR spectroscopy were performed in 14 patients with clinically definite multiple sclerosis (MS). Prominent resonances in the 0.5-2.0-ppm region were seen in the spectra of six of nine gadopentetate dimeglumine-enhanced plaques in seven patients. These resonances were presumed to originate in lipids and other myelin breakdown products. Similar resonances were detected in only seven of 21 unenhancing plaques. The more frequent presence of such signals in the gadolinium-enhanced regions indicates that myelin breakdown is often associated with the inflammation that occurs in early stages of MS plaque evolution. It remains uncertain, however, whether active inflammation as indicated by gadolinium enhancement is a necessary precursor of myelin breakdown as detected at MR spectroscopy. Quantitative spectral analysis did not indicate statistically significant differences in N-acetyl aspartate and choline levels relative to creatine plus phosphocreatine between healthy volunteers and MS patients. PMID- 1627861 TI - MR imaging detection of calcified intracranial lesions and differentiation from iron-laden lesions. AB - Magnetic susceptibility variation caused by calcium permits limited detection of intracranial calcifications and/or their distinction from iron-laden lesions with spin-echo or gradient-echo magnetic resonance (MR) techniques. The magnetic susceptibility sensitivity of phase imaging has been used to detect iron-laden lesions. A new approach that combines the magnetic susceptibility sensitivity of both gradient-echo and phase imaging to yield greater imaging sensitivity to calcium is presented. Two-dimensional fast low-angle shot (FLASH) gradient-echo imaging with phase image reconstruction (gradient-echo phase [GEP]) was used at 1.0 and 1.5 T. Twelve patients with computed tomography-proved calcified intracranial lesions (greater than or equal to 200 HU) and seven patients with iron-laden intracranial lesions having a characteristic appearance on T1- and T2 weighted and FLASH MR images were studied. The GEP imaging technique helped detect calcified intracranial lesions (greater than or equal to 200 HU) and helped distinguish them from iron-laden lesions. PMID- 1627862 TI - Gadolinium-enhanced high-resolution MR angiography with adaptive vessel tracking: preliminary results in the intracranial circulation. AB - To overcome problems associated with poor contrast between vessels and background tissue in time-of-flight magnetic resonance angiography, the role of intravenous gadopentetate dimeglumine in conjunction with a postprocessing adaptive vessel tracking scheme was studied. Vessel tracking makes it possible to discriminate arteries from veins, to prevent problems associated with other bright tissues on maximum-intensity projections, and to increase the signal-to-noise ratio. Short, asymmetric, velocity-compensated field echoes were used in conjunction with high resolution imaging techniques to spatially discriminate between adjacent vessels and stationary background tissue. Gadopentetate dimeglumine was shown to be useful for visualization of small vessels, aneurysms, and regions of slow flow, when used with this post-processing scheme. PMID- 1627863 TI - Analysis of flow effects in echo-planar imaging. AB - The effects on the phase of spins moving during echo-planar imaging (EPI) acquisition were studied. Standard single-shot and interleaved multishot blipped EPI acquisitions were considered, assuming either high gradient strength and slew rates or standard gradient strength and slew rates. A spiral k-space trajectory was also considered. Flow components in the section-select and phase- and frequency-encoding directions were analyzed separately. While the effect of flow in the section-select direction is identical to that in a standard two dimensional Fourier transform (2DFT) acquisition, flow in the phase- or frequency encoding directions can have substantial effects on the image, different from that in 2DFT imaging. The magnitude of these effects, which include displacement, distortion, and/or ghosting of vascular structures, is analyzed and predicted for a given velocity and direction of flow, the specific acquisition sequence, and the strength and slew rate of the gradients. For example, 50-cm/sec flow along the phase-encoding direction can cause a blurring of 1.25 cm full width at half maximum for blipped EPI with high-strength gradients, assuming a 40-cm field of view and 64 x 64 matrix. PMID- 1627864 TI - Mitral and aortic valvular flow: quantification with MR phase mapping. AB - When magnetic resonance phase mapping is used to quantitate valvular blood flow, the presence of higher-order-motion terms may cause a loss of phase information. To overcome this problem, a sequence with reduced encoding for higher-order motion was used, achieved by decreasing the duration of the flow-encoding gradient to 2.2 msec. Tested on a flow phantom simulating a severe valvular stenosis, the sequence was found to be robust for higher-order motion within the clinical velocity range. In eight healthy volunteers, mitral and aortic volume flow rates and peak velocities were quantified by means of phase mapping and compared with results of the indicator-dilution technique and Doppler echocardiography, respectively. Statistically significant correlations were found between phase mapping and the other two techniques. Similar studies in patients with valvular disease indicate that phase mapping is also valid for pathologic conditions. Phase mapping may be used as a noninvasive clinical tool for flow quantification in heart valve disease. PMID- 1627865 TI - MR angiography of lower-extremity arterial disease: preliminary experience. AB - Nineteen patients underwent magnetic resonance (MR) angiography for evaluation of lower-extremity arterial disease. The underlying conditions included atherosclerotic occlusive disease in 12 patients, femoral or popliteal aneurysms in four, and bypass graft stenoses or occlusion in four. In the patients with occlusive disease, the iliac and femoropopliteal vessels were classified as patent, moderately stenotic, severely stenotic, or occluded. Fifteen of 16 occlusions (accuracy = 94%) were correctly classified. In the one missed case, there was a long delay between MR angiography and x-ray angiography and it is likely that the occlusion occurred during the interval. Three of five severe stenoses were correctly classified with MR angiography. In two cases of iliac artery stenosis, there was a signal void at the point of maximal stenosis, which on the basis of anatomic features could be recognized as severe stenosis rather than an occlusion. Three of four moderate stenoses were correctly classified. Correlation with x-ray angiography or surgery demonstrated the ability of MR angiography to accurately depict the status of runoff vessels. PMID- 1627866 TI - Detection of zonal renal ischemia with contrast-enhanced MR imaging with a macromolecular blood pool contrast agent. AB - The potential of magnetic resonance (MR) imaging enhanced with albumin (gadolinium diethylenetriaminepentaacetic acid [DTPA])35, a macromolecular blood pool marker, for detection of focal changes in renal perfusion was studied in a myoglobinuric acute renal failure (ARF) model in the rat. T1-weighted spin-echo postcontrast images of injured kidneys at 3 hours after glycerol injection showed three distinct zones: a strongly enhanced outer cortex, a low-intensity inner cortex, and a strongly enhanced medulla. The distinct band of low intensity in the inner cortex indicated zonal decreased blood volume, corresponding to published microsphere data showing zonal low perfusion in the inner cortex. Contrast differences between parenchymal zones were significant for at least 30 minutes. No focal ischemic changes could be delineated on nonenhanced images. Enhanced and nonenhanced images of injured kidneys obtained at 24 hours after glycerol injection revealed no zonal differentiation. Contrast-enhanced MR imaging data in this ARF model correlated well with pathologic data and microsphere perfusion results. Contrast-enhanced characterization of the ischemic phase of renal injury with MR imaging may improve specificity for the diagnosis of ARF and may serve as a marker for therapeutic intervention. PMID- 1627867 TI - Pelvic imaging with phased-array coils: quantitative assessment of signal-to noise ratio improvement. AB - The signal-to-noise ratios (S/Ns) of two different pelvic magnetic resonance (MR) imaging phased arrays were compared with that of the body coil. Each array consisted of two coils placed anteriorly and two posteriorly, oriented transversely in one array and longitudinally in the other. S/N measurements were obtained in an adjustable water-filled phantom that stimulated the shape and radio-frequency loading effects of various-size patients. Depending on the simulated anterior-posterior thickness of the patient, the S/N produced by the longitudinal array ranged from 2.3 to 3.1 times higher than that of the body coil. The S/N of the transverse array was 3.1 to 3.4 times higher. The increased coil sensitivity permits imaging with shorter acquisition times, smaller fields of view, finer resolution, and/or thinner sections. Two examples in patients demonstrate the enhanced imaging capability of the phased arrays. PMID- 1627868 TI - Centric phase-encoding order in three-dimensional MP-RAGE sequences: application to abdominal imaging. AB - Three-dimensional (3D) magnetization-prepared rapid gradient-echo imaging has been proposed as a method for improving signal-to-noise ratio (S/N) and contrast to-noise ratio (C/N) in rapid abdominal imaging. Originally, a standard sequential phase-encoding order was proposed. In the present study, two approaches to a 3D centric phase-encoding order are presented: (a) application of the two-dimensional (2D) centric order to one of the 3D encoding directions, and (b) an interleaved square spiral order, which is the segmented 3D analog of the 2D centric order. With use of simulation, phantom, and volunteer results, the proposed 3D centric methods are compared in terms of S/N, C/N, and artifacts to the 3D sequential method and 2D magnetization-prepared methods. The second centric approach was found to be superior to the first; however, in general, the 3D technique was found to be inferior to the 2D technique for abdominal imaging because of motion artifact in the 3D image set caused by misregistration among the multiple breath holds required. PMID- 1627869 TI - Quantitation of total metastatic tumor volume in the rat liver: correlation of MR and histologic measurements. AB - Assessing tumor response to chemotherapy in the liver has always been difficult. Most investigators estimate tumor volume as either a product of the two perpendicular diameters of a tumor nodule, or, in animal studies, simply count surface tumor nodules. The authors evaluated magnetic resonance (MR) imaging as a technique for determining absolute tumor volume in the liver in an animal model. Specifically, histologic volumetric and MR imaging measurements of tumor and liver volumes were quantitatively compared over a wide range of tumor burdens in a rat model of hepatic metastasis of a colorectal carcinoma. Twenty-three rats were imaged, with two different section thicknesses used in each animal. Both section thicknesses showed highly significant correlations between MR and histologic measurements for both tumor and liver volumes (P less than .001). MR imaging may be useful for noninvasively quantifying tumor burden and temporal response of metastatic disease in the liver to novel antineoplastic regimens. PMID- 1627870 TI - Detection of acute and treated lesions of hepatosplenic candidiasis: comparison of dynamic contrast-enhanced CT and MR imaging. AB - Dynamic contrast-enhanced computed tomography (CT) was compared with 1.5-T magnetic resonance (MR) imaging with FLASH (fast low-angle shot), gadolinium enhanced FLASH (Gd-FLASH), and T2-weighted fat-suppression (T2FS) sequences in 11 patients with hematologic malignancies, five with biopsy-confirmed hepatosplenic candidiasis treated with antifungal chemotherapy and six with a clinical history suggestive of acute hepatosplenic candidiasis. CT and MR images were separately interpreted in a prospective fashion. MR imaging showed lesions compatible with candidiasis in the liver in six patients, the spleen in five, and the kidneys in one. CT showed candidiasis-compatible lesions in the liver in three patients and the spleen in one; no renal lesions were shown. Differences between acute and treated candidal lesions were observed. Gd-FLASH images showed the most liver lesions (n = 106), followed by FLASH (n = 85), T2FS (n = 20), and CT (n = 18). MR imaging performed better than CT in distinguishing candidal hepatic lesions from recurrent lymphoblastic lymphoma in one patient and from hepatic infarcts in another. The results suggest that MR imaging may be superior to CT in detecting lesions of hepatosplenic candidiasis. PMID- 1627871 TI - Noise and artifact comparison for Fourier and polynomial phase correction used with Fourier reconstruction of asymmetric data sets. AB - Two processes of phase correction, Fourier phase mapping and second-order polynomial phase fitting, are compared in combination with four different schemes for Fourier reconstruction of asymmetric data, using one-dimensional simulations and two-dimensional human head data. Polynomial phase correction provides systematically less image noise and is much less affected by localized phase differences caused by object edges and motion. PMID- 1627872 TI - Selective versus nonselective preparation pulses in two-dimensional MP-RAGE imaging of the liver. AB - The use of a section-selective preparation pulse in two-dimensional (2D) T1 weighted magnetization-prepared rapid gradient-echo (MP-RAGE) imaging of the liver was investigated. The images were compared with those obtained with a nonselective pulse. The performances of the sequences were evaluated in 11 patients with 12 focal liver lesions, and lesion-liver and lesion-vessel signal difference-to-noise ratios (SD/Ns) were calculated. With the section-selective preparation pulse, small lesions were better differentiated from vessels, and multiple, consecutive images could be obtained at shorter intervals. The mean lesion-liver SD/N was slightly but not significantly greater for images obtained with a selective pulse, while the lesion-vessel SD/N was significantly greater (P less than .01). It is concluded that a section-selective preparation pulse can improve the clinical utility of the 2D MP-RAGE sequence in the evaluation of focal liver disease. PMID- 1627873 TI - Optimization of three-dimensional T1-weighted gradient-echo imaging of the cervical spine. AB - Various parameters of the three-dimensional (3D) T1-weighted magnetization prepared rapid acquisition gradient-echo (MP-RAGE) sequence were evaluated to improve spatial resolution while maintaining T1 contrast and a short examination time in imaging of the cervical spine in volunteers. The most dramatic improvements in image resolution occurred by decreasing section thickness to 1.2 mm and increasing the in-plane matrix to 192 x 256, with a 230-mm field of view. The increase in imaging time due to the increased matrix was offset by the elimination of the preparation pulse and wait time, without dramatic changes in contrast-to-noise ratio or overall image quality. Optimum parameters included elimination of the preparation pulse and wait time, 12 degrees flip angle, 192 x 256 matrix, 1.2-mm section thickness, nonselective excitation (coronal acquisition), RF spoiling, and standard k-space ordering, for an examination time of 5 minutes 21 seconds. PMID- 1627874 TI - Cardiovascular MR imaging: current level of clinical activity. AB - Relative to other clinical magnetic resonance (MR) imaging activities, cardiovascular (CV) MR imaging has been slow to demonstrate a clinical presence. To better understand the present situation in clinical CV MR imaging, a survey of Society for Magnetic Resonance Imaging (SMRI) members was conducted. A large majority (78%) of the 90 sites responding to the survey reported clinical activity in CV MR imaging. Of these 70 sites, 46% restricted such activity to routine clinical work, while 3% restricted it to clinical research. The remaining 51% conducted both. At all clinical sites, the overall frequency of performance of clinical CV MR imaging was variable (mean, 4.2 and 13.8 cases per month at routine-only and combined routine-research sites, respectively). In clinical CV studies, gated static, multi-level spin-echo and dynamic gradient-echo (cine) techniques were most common. At the 68 sites involved in routine clinical CV MR imaging, primarily anatomic studies composed a much higher proportion of the total (mean, 86%) than primarily functional studies. The evaluation of acquired thoracic aortic disease, congenital cardiac malformation, and para- or intracardiac mass were the most prevalent anatomic indications overall. Approximately half of the same sites assessed functional aspects of CV disease. The assessment of ventricular dysfunction and valvular dysfunction were the most common functional objectives. The survey indicated that the level of clinical activities in CV MR imaging was low and that most responding sites were involved in clinical CV MR imaging primarily for detection and delineation of anatomic abnormalities. PMID- 1627875 TI - Amplification of serotonin-induced arterial contractions with thrombin. AB - The purpose of this study was to determine if exposure of arteries to thrombin increases arterial sensitivity to serotonin and could thereby promote vasospasm. Rings of rabbit abdominal aorta, with endothelium intact or removed, were pretreated with vehicle or thrombin (2.5 U/mL). Thereafter, arterial contractions in response to cumulative additions of serotonin were recorded. Arterial contractions were expressed as a percentage of maximal potassium chloride-induced contractions. Arterial sensitivity was expressed as the EC50, the concentration of serotonin that produced a half-maximal contraction. Exposure of aortic rings to thrombin alone produced contractions of 11% and 22% for rings with and without endothelium, respectively. Removal of the endothelium had no effect on maximal serotonin-induced contractions (93% with endothelium vs 98% without). In contrast, maximal serotonin-induced contractile force was increased after pretreatment with thrombin (107% vs 121% for rings with and without endothelium, respectively; P less than .01). Arterial sensitivity to serotonin was not affected by the removal of endothelium. However, thrombin pretreatment increased (P less than .01) arterial sensitivity to serotonin 2.6-fold and 4.7-fold for rings with and without endothelium, respectively. The results of this study demonstrate that arterial contractions due to serotonin are amplified by thrombin and suggest that vasospasm may be more likely to occur at sites in arteries where the endothelium is absent and both thrombin and serotonin are present. PMID- 1627876 TI - Hepatic ablation with use of radio-frequency electrocautery in the animal model. AB - The potential of percutaneous radio-frequency (RF) electrocautery hepatic ablation was evaluated in the animal model. RF hepatic ablation was performed under ultrasound (US) guidance in the liver of 10 swine with use of a specifically designed needle. The needle was placed through the liver capsule, and ablation was performed after isolating the liver at laparotomy. Animals were killed immediately (n = 4), at 1 week (n = 1), 2 weeks (n = 3), or at 5 weeks (n = 2). The US findings were correlated with the pathologic results in the animal livers. RF hepatic ablation was successfully performed in the animal model without complications. Lesions in the animal livers were typically 1 x 2 cm, which initially appeared highly echogenic on US scans. These images corresponded to an area of hepatic necrosis. The lesions became less echogenic shortly after initial treatment but could still be visualized with US at 5 weeks. At histologic study at 5 weeks, the treated livers showed central debris, a larger area of necrotic liver, and a zone of granulation tissue surrounded by a fibrotic capsule. No complications were encountered. RF hepatic ablation shows future promise in treatment of hepatic neoplasms. PMID- 1627877 TI - Enhancement of fibrinolysis with ultrasound energy. AB - The effect of ultrasound energy on fibrinolysis of artificial thrombus in vitro was investigated. Thrombi produced by the Chandler loop method were exposed to low-energy ultrasound (5,000-6,000 Pa) in an ultrasound bath (48 kHz) for 60 seconds. Fibrinolysis with urokinase was enhanced from 40.6% +/- 1.8% to 59.2% +/ 2.6% (mean +/- standard deviation) with ultrasound exposure after a 60-minute incubation. Ultrasound alone without urokinase resulted in no fibrinolysis. In a second experiment, a newly developed miniature ultrasound-emitting ceramic element (2 x 1 x 5 mm) was attached to the tip of a catheter. Ultrasound exposure (225 kHz) from this device markedly enhanced fibrinolysis with urokinase from 8.9% +/- 1.5% to 37.3% +/- 0.8% (total ultrasound exposure 60 seconds, intensity 30 mW/cm2) after a 30-minute incubation. After a 120-minute incubation, fibrinolysis with ultrasound exposure was 61.1% +/- 1.8% versus 46.7% +/- 0.5% for the unexposed group. Ultrasound enhancement of fibrinolysis was less pronounced with longer incubation time (60 or 120 minutes). Ultrasound energy enhanced fibrinolysis with urokinase, especially in the early phase of lysis. This new device may shorten the time needed to complete fibrinolysis and reduce total drug dosage needed for treatment of thromboembolic diseases. PMID- 1627878 TI - Endoluminal thermal occlusion of the ureter with the electromagnetic field focusing device. AB - The authors attempted ureteral occlusion by means of heat application in nine ureters (24 sites) of New Zealand White rabbits with the electromagnetic field focusing (EFF) device. The EFF device generates heat at the tip of a grounded probe by focusing eddy currents that have been induced within the tissues by an external radio-frequency field. The power settings were varied from 30 to 150 W. Heat was applied at multiple sites in each ureter. Immediate functional occlusion was seen in all nine ureters. Long-term complete occlusion was seen in six ureters at power settings ranging from 40 to 150 W, while long-term partial occlusion was seen in two ureters at 30-50 W. All sites at 30 W resulted in partial occlusions. Perforation of the ureter resulted in urinoma formation in one ureter at a site that was treated with 150 W. The EFF device can be used to endoluminally occlude the ureter by causing a fibrotic reaction to thermal injury. The effective power range for this application appears to be 40-100 W. PMID- 1627879 TI - Percutaneous ureteral occlusion with use of Gianturco coils and gelatin sponge. Part I. Swine model. AB - An animal model was developed to study ureteral occlusion produced by steel coils and gelatin sponge. A coil nest was formed in the ureter, and in all but one pig, gelatin sponge pledgets were incorporated in the coil nest. Animals were killed at 2 hours, 1 week, 1 month, and 2 months. High-grade obstruction was present immediately following the procedure in all animals and was documented to be persistent by means of antegrade nephrostograms obtained just prior to death. At gross examination after death, ureteral thickening and strictures were evident. Histologic studies helped confirm the presence of acute and chronic inflammatory changes. In the in vivo model, gelatin sponge was not found necessary for acute ureteral occlusion. However, in an ancillary in vitro study in which a rigid plastic tube was used, gelatin sponge was necessary in addition to coil occlusion to provide acute total obstruction. The authors' findings suggest that in a compliant ureter, coil occlusion alone produces sufficient mechanical occlusion. Long-term obstruction is probably due to mechanical obstruction and stricture formation. PMID- 1627880 TI - Percutaneous ureteral occlusion with use of Gianturco coils and gelatin sponge. Part II. Clinical experience. AB - A previous report described the use of coils and gelatin sponge pledgets as a means of producing ureteral occlusion to achieve urinary diversion in patients with urinary fistulas. The authors have performed this procedure in nine ureters of six patients. Five of the patients had urinary leaks with extensive pelvic tumor, and one had severe chronic cystitis. Ureters were occluded with use of Gianturco coils and gelatin sponge pledgets placed via a sheath through a percutaneous nephrostomy tract. The procedure was successful in all patients as judged by means of antegrade nephrostogram or intravenous pyelogram and by marked improvement or complete resolution of symptoms. PMID- 1627881 TI - Hemorrhagic complication of transgluteal pelvic abscess drainage: successful percutaneous treatment. PMID- 1627882 TI - Spinal dural arteriovenous anomalies. AB - The clinical data, radiologic findings, and treatment in 14 cases of spinal dural arteriovenous (AV) anomaly were reviewed. All patients had typical findings of feeding artery, nidus, and draining vein on spinal angiograms. Radiologic diagnosis of spinal AV malformation was first made after myelography in 13 cases and after magnetic resonance (MR) imaging in one case. Thirteen patients underwent embolization; one patient underwent repeat embolization 14 months after the first procedure. The other patient underwent surgical ligation. All patients had clinical improvement after treatment. A high index of clinical suspicion, a complete myelographic examination or an MR image of good quality, and a properly performed complete spinal angiographic study are important for early diagnosis. Embolization may be the treatment of choice. For best results, the feeding artery next to the nidus and the draining vein close to the nidus should be occluded, and the nidus itself should be obliterated. PMID- 1627883 TI - Infantile hepatic hemangioendotheliomas: significance of portal venous and systemic collateral arterial supply. AB - This report describes four infants with hepatic hemangioendotheliomas and cardiac failure who had extensive portal venous and systemic collateral arterial supply complicating hepatic arterial embolization. One patient with diffuse hepatic hemangioendothelioma and extensive portal vein supply but minimal systemic collateral arteries showed no improvement after technically successful hepatic artery embolization and died with disseminated intravascular coagulation and sepsis. A second infant with extensive portal vein and collateral supply died without undergoing embolization. Two patients had portal vein-hepatic vein fistulas as well as an extensive systemic arterial supply. Both infants tolerated staged hepatic and collateral artery embolization, although one patient died of congestive heart failure, probably related to pulmonary hemangiomas. The authors conclude that angiographic study of the potential collateral vessels and portal venous circulation should be performed before embolization. Patients with shunting from the portal vein to the hepatic vein and minimal systemic arterial collateral circulation should not undergo hepatic artery embolization. PMID- 1627884 TI - Hemobilia after percutaneous transhepatic biliary drainage: treatment with transcatheter embolotherapy. AB - Thirteen of 333 patients who underwent percutaneous biliary drainage (PBD) developed severe hemobilia. Hepatic arteriography successfully demonstrated the source of hemorrhage in all 13 patients. Lesions included hepatic artery pseudoaneurysm in nine, hepatic artery-bile duct fistulas in four, and a hepatic artery-portal vein fistula in one patient. Hemobilia occurred from 1 day to 1.8 years (mean, 100 days) following catheter placement. Embolization agents used included Hilal embolization microcoils, occluding spring emboli, cyanoacrylate, detachable balloons, and gelatin sponge pledgets. A single agent was used in eight cases (62%), multiple agents were used in four cases (31%), and in one case (7%), spontaneous thrombosis of the pseudoaneurysm occurred during catheter manipulation. In five patients, the source of the hemorrhage could only be demonstrated following removal of the biliary catheter(s) over guide wire(s). Initial embolization was successful in stopping hemobilia in 12 patients. One patient required repeat embolization after 4 months. Postembolization complications included hepatic abscess formation in two patients and a sterile hepatic infarct in one patient. This series indicates that transcatheter embolotherapy is an effective method for the treatment for severe hemobilia. PMID- 1627885 TI - Nonoperative treatment of enteric fistulas: results in 53 patients. AB - Fifty-three patients with enterocutaneous fistulas were treated nonoperatively. While most of the fistulas resulted as a complication of surgery, other causes included inflammatory disease, trauma, and malignancy. Fistulas originated from the esophagus (n = 4), stomach (n = 4), duodenum (n = 5), small bowel (n = 27), colonic-small bowel anastomosis (n = 2), colon (n = 10), and Hartmann pouch (n = 1), and included both high-output (n = 29) and low-output (n = 24) types. Nonoperative management resulted in spontaneous fistula closure in 57%. Most of the spontaneous closures (83%) occurred within 2 months of treatment. Spontaneous closure rates were similar for low-output and for high-output fistulas (52% vs 63%), but the treatment duration was longer for high-output than for low-output fistulas (mean treatment duration, 17 days vs 41 days). Colonic fistulas were particularly difficult to manage and closed spontaneously in only 10% of patients (one of 10). PMID- 1627886 TI - Abdominal abscesses associated with enteric fistulas: percutaneous management. AB - For many years, surgical dictum stated abdominal fistulas should be treated by means of surgical excision. Recent advances in percutaneous techniques have altered this. The authors reviewed 150 consecutive abdominal abscesses drained percutaneously over a 36-month period. Among these, 24 patients were found to have 26 fistulous communications to bowel, the pancreatic duct, or the biliary system. Initial drainage of their abscesses was performed in the hospital, but 17 of 24 patients were discharged with a tube in place and were followed up as outpatients. The duration of drainage ranged from 4 days to 3 months. Fistulas healed in 21 of 24 patients (88%) without surgical intervention. Complications were few and included inadvertent dislodgment requiring tube replacement (two patients) and inadvertent puncture of the transverse colon (one patient). Treatment of abdominal abscesses with fistulas by means of percutaneous methods is reliable and safe. Hospital stay may be minimized with outpatient management after drainage. PMID- 1627887 TI - Biliary obstruction: treatment with self-expanding metal prostheses. AB - The authors percutaneously and endoscopically inserted 58 Wallstent endoprostheses in 42 consecutive patients with benign and malignant obstructive biliary stenoses. The three patients with benign obstructive jaundice were followed up for 48 months. Two of the stents occluded due to sludge formation, prompting percutaneous reentry. The 39 patients with malignant disease were followed up for 18 months. Twenty-six of these patients died 3 days to 1.5 years (mean, 133 days) after the procedure. Thirteen are alive after 2-12 months (mean, 242 days). Recurrent jaundice occurred in 11 patients (28%): in four patients due to tumor growth over the proximal end of the stent, in one patient due to excessive gallbladder hydrops, and in six patients due to liver failure. Although autopsy investigations revealed the possibility of tumor growth onto the inner surface of the stent through the stainless steel mesh of the endoprosthesis, stent occlusion by tumor ingrowth into the lumen was not encountered. PMID- 1627888 TI - Use of the external jugular vein approach for transvenous liver biopsy. AB - Transjugular liver biopsy (TJLB) with use of a right external jugular vein (EJ) approach obviates a deep neck puncture, thereby reducing the risk associated with the procedure in patients with severely disordered coagulation. The EJ approach was successful in 21 of 24 consecutive patients referred for TJLB (88%). The approach was unsuccessful in three cases due to thrombosis or congenital absence of the right EJ. TJLB via the right EJ was successful in all cases in which EJ access could be obtained. In the 21 successful cases, the EJ approach simplified the procedure and shortened its duration. There were no procedure-related complications attributable to the EJ approach. The authors now use the EJ route routinely for patients undergoing TJLB and other transjugular procedures in their laboratory. The EJ approach is particularly recommended in patients with impaired coagulation. PMID- 1627889 TI - Peroral radiographic placement of biliary stents. AB - The authors describe a modification of peroral-transhepatic placement of biliary stents for patients with malignant biliary obstruction. A stent is "pulled" into place perorally. The procedure can be performed with simple, readily available commercial materials. An endoscopist is not required. This method is cost effective, less cumbersome, and easier to perform than the standard methods. In the authors' four cases, this modified approach appears equally effective. PMID- 1627890 TI - Percutaneous interventions in the thorax. Seventh annual Charles Dotter Memorial Lecture. PMID- 1627891 TI - Prebiopsy wire localization of a small peripheral lung nodule. AB - The authors report a case in which metallic microcoils were placed under computed tomographic guidance as wire localization devices prior to an excisional lung biopsy. The technique and advantages are somewhat analogous to those of pre excisional biopsy of a breast mass with use of wire localization performed under mammographic guidance. This technique was useful for localizing the mass as well as limiting the amount of surgically excised tissue in this case. Additionally, the postexcision specimen radiograph helped confirm that the lung lesion in question had been removed. This may be a useful preoperative technique prior to excisional biopsies of small lung lesions that may not be accessible with percutaneous biopsy techniques and in selected cases such as in patients with diseased lung parenchyma surrounding a lesion or in patients in whom the lesion to be excised is adjacent to the pulmonary root. PMID- 1627892 TI - Gunther vena caval filter: clinical appraisal. AB - The mechanical stability of the Gunther filter, caval patency, and complications related to filter placement were evaluated in 33 patients. Indications for placement included recurrent pulmonary embolism despite anticoagulation (n = 24) and contraindication to anticoagulation (n = 5). Four filters were placed prior to pulmonary lysis. Filters were positioned via the transfemoral route in 31 patients and via the transjugular route in two. Placement was complicated by pneumothorax in one case and faulty filter position in another. Patients were followed up for 52 months (mean, 12.1 months). Four patients died of nonembolic complications; three patients were lost to follow-up. Among the remaining 26 patients, caudal migration (3-6 cm) occurred in 19 (73%), cephalic migration into the atrium occurred in one, the inferior vena cava occluded in five, and struts perforated the caval wall in five. Pulmonary embolism recurred in one patient. In 11 cases, thrombus caught inside the basket was revealed with computed tomography; in one case a 7-cm floating thrombus was observed. The authors conclude that use of the Gunther filter cannot be recommended because of the high prevalence of complications. PMID- 1627893 TI - Complications of the nitinol vena caval filter. AB - Simon nitinol vena caval filters were placed percutaneously in 20 patients. Follow-up (average, 14 months) data were available for 16 patients, and four patients were lost to follow-up. There were no proved or suspected cases of pulmonary embolism after filter insertion. Complications encountered included caval penetration (n = 5, one acute and four at follow-up), caval thrombus (n = 4, two determined radiologically and two clinically), postplacement deep venous thrombosis (n = 2, one radiologic and one clinical), filter migration (n = 1), and delayed fracture of a filter leg (n = 2). Although no deaths or significant morbidity resulted from any complication, the relatively high complication rate, especially of significant caval penetration (documented in 25% of filter insertions), merits continued short- and long-term assessment of patient status after filter placement. PMID- 1627894 TI - Use of the Gianturco self-expanding stent in stenoses of the superior and inferior venae cavae. AB - Twenty-eight patients with severe superior and inferior vena cava syndromes were treated with self-expandable Gianturco stents. Nineteen patients responded, seven did not respond, and two were unevaluable. Fourteen of the 19 who responded had complete or near complete resolution of their syndrome, and five had a partial remission. Five of the responders did not derive any benefit from stent placement because of additional problems that led to their death within 3 weeks of the stent placement procedure. The main cause for failure was the relatively weak expansile force of the stent. Complications included stent migrations without untoward effects in one patient, stent misplacement in one patient, fracture of the stent wire in two patients, and hemorrhage that could be attributed to the stent in one patient. This uncontrolled study suggests that caval obstruction syndromes in some patients may be effectively palliated with Gianturco stents. PMID- 1627895 TI - US guidance for vascular access. Technical note. AB - Real-time ultrasonography (US) is frequently used to access the biliary tree, urinary system, and pleural cavity, as well as abscesses and other fluid collections, but is rarely used to access blood vessels. This article describes the clinically indicated circumstances and technical aspects of US-guided access to veins and arteries. The authors' experience suggests that appropriate use of this modality significantly simplifies vascular access difficulties, reduces procedure time and morbidity, and is cost-effective. PMID- 1627896 TI - Color Doppler flow imaging appearance of a popliteal venous aneurysm. AB - Popliteal venous aneurysms are rare lesions that usually become evident when thrombus from within the aneurysm embolizes to the lungs. The authors report an unusual case in which the patient presented without thromboembolic complications. The appearance of a popliteal venous aneurysm at color Doppler flow imaging is described. PMID- 1627897 TI - Summary of workshop on drinking water fluoride influence on hip fracture on bone health. (National Institutes of Health, 10 April, 1991) PMID- 1627898 TI - A case-control study of hip fracture: evaluation of selected dietary variables and teenage physical activity. AB - Recent diet, teenage physical activity and teenage calcium consumption were examined as risk factors for hip fracture in a case-control study. Cases were 161 white women admitted to one of 30 participating hospitals with a first hip fracture. Controls included 168 white women from general and orthopedic surgical services frequency-matched to cases by age group and hospital. Information on exposure to possible risk factors was obtained by in-person interview. No association was found between recent intake of calcium, phosphorus, protein, vitamin C or caffeine and hip fracture. Also, teenage calcium intake and milk drinking were not related to hip fracture risk. Recreational activities in adolescence and early adulthood appeared to afford protection against hip fracture. The highest quartile of recreational activity (greater than or equal to 4 times/week) was associated with an odds ratio of 0.24 (95% confidence interval 0.08-0.75) relative to the lowest quartile (less than 1 time/week). PMID- 1627900 TI - Dual-energy X-ray absorptiometry in normal women: a cross-sectional study of 717 Finnish volunteers. AB - The bone mineral density (BMD) of the lumbar spine and proximal femur was measured using dual-energy X-ray absorptiometry in 717 healthy women aged 20-70 years. The maximal mean BMD was found at the age of 35-39 years in the spine and at the age of 20-24 in the femoral neck and Ward's triangle. No significant change in lumbar BMD was found from the age of 20 to 39 years. The spinal BMD values were relatively stable from age 20 to 39 years, whereas a linear decrease in BMD in the femoral neck and Ward's triangle was already apparent in the youngest age group (20-24 years). The major fall in BMD in all sites was related to the menopause. The overall decreases in BMD from the peak values to those at age 65-70 years were 20.4%, 19.0% and 32.6% in the lumbar spine, femoral neck and Ward's triangle, respectively. The correlation of trochanteric BMD with age was poor. BMD was positively correlated with weight in all measurement sites. Nulliparity was found to be a risk factor for osteoporosis. The present study confirmed that the menopause has a significant effect not only on spinal BMD but also on femoral BMD. Lumbar BMD was lower and BMDs in the proximal femur were higher in Finnish women than in white American women. This emphasizes the importance of national reference values for BMD measurements. PMID- 1627899 TI - Impaired bone formation in male idiopathic osteoporosis: further reduction in the presence of concomitant hypercalciuria. AB - We present iliac bone histomorphometric data and related biochemical data from 16 nonalcoholic men (50 +/- 11 (SD) years) referred for evaluation of spontaneous skeletal and/or appendicular fractures and reduced spinal bone density. All men were eugonadal and had no known underlying disorder associated with osteopenia. For the group, mean serum chemistry values were within normal limits including immunoreactive parathyroid hormone, osteocalcin and serum 1,25-dihydroxyvitamin D [1,25(OH)2D]. Nine men demonstrated hypercalciuria (greater than or equal to 0.1 mmol/kg per day) while on a constant metabolic diet of 20 mmol/day Ca. Their 24 hour urinary calcium was significantly greater than that for the remaining 7 men (7.4 +/- 1.6 vs. 5.0 +/- 0.8 mmol/day, p = 0.003), as was their calciuric response to a 1 g oral calcium load (0.23 +/- 0.06 vs. 0.15 +/- 0.05 Ca/creatinine, p = 0.042). Serum parameters (including parathyroid hormone and 1,25(OH)2D) of hypercalciuric and normocalciuric men were not significantly different. Histomorphometric indices for cancellous bone demonstrated significant differences between the entire group of osteoporotic men and age-adjusted normal values for bone volume (11.4 +/- 4.0% vs. 23.2 +/- 4.4%), osteoid surface (5.6 +/ 3.9% vs. 12.1 +/- 4.6%), osteoblastic surface (2.0 +/- 2.3% vs. 3.9 +/- 1.9%), and mineralizing surface (1.9 +/- 2.4% vs. 5.1 +/- 2.7%); there were also significant differences in bone formation rate (total surface referent) (0.004 +/ 0.001 vs. 0.011 +/- 0.006 mm3/mm2 per year). Compared with the normocalciuric group the 9 hypercalciuric men had significantly lower osteoblastic surfaces (1.6 +/- 1.9% vs. 2.5 +/- 2.6%) and mineralizing surfaces (1.4 +/- 1.5% vs. 2.7 +/- 3.2%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627902 TI - An evaluation of dual-energy X-ray absorptiometry and comparison with dual-photon absorptiometry. AB - Dual-photon absorptiometry (DPA) is a well-established procedure for measuring bone mineral density (BMD). Recently, dual-energy X-ray absorptiometry (DXA) has become available, which has the ability to measure BMD both regionally and in the total body (TB). We have evaluated the in vivo and in vitro precision of a DXA instrument and compared it with a DPA instrument with similar software characteristics. The short-term precision of BMD measurements using DXA was assessed in 65 postmenopausal women who had duplicate scans performed, with repositioning between scans. Precision was 0.9% in the lumbar spine and 1.4% in the femoral neck. The midterm precision of DXA was compared with DPA by scanning 10 volunteers a mean of four times over 24 weeks, on both instruments. The precision of the bone mineral content (BMC) and area measurements was significantly better (P less than 0.05) with DXA than with DPA. Long-term in vitro precision was assessed by scanning an aluminium spine phantom over 42 weeks, and a cadaveric sample over 52 weeks, on both instruments. Precision was similar using the aluminium phantom, but was significantly improved (P less than 0.001) when using DXA for scanning the cadaveric sample. Highly significant correlations (all P less than 0.001) of BMD, BMC and area measurements were observed when 70 volunteers were scanned on both instruments. However, there was a systematic difference in BMD values between the instruments. The precision of TB composition measurements assessed in 16 volunteers, over a 16-week period, were TB BMD 0.65%, TB lean tissue 1.47%, and TB fat tissue 2.73%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627901 TI - Calcitonin metabolism in senile (type II) osteoporosis. AB - The exact role of calcitonin (CT) in the pathogenesis of senile (Type II) osteoporosis remains unknown. Whole plasma calcitonin (iCT) and extracted monomeric calcitonin (eCT) basal levels, metabolic clearance rate (MCR) and production rate (PR) of iCT and eCT were measured in 41 postmenopausal women, including 14 hip fractures (OP II) and 27 healthy controls. No significant difference appeared for basal iCT levels between OP II (mean +/- SEM: 41.9 +/- 3.4 pg/ml) and controls (mean +/- SEM: 46.2 +/- 5 pg/ml). eCT basal levels were similar in OP II (mean +/- SEM: 5.42 +/- 0.5 pg/ml) and in controls (mean +/- SEM: 7.3 +/- 0.7 pg/ml). MCR were similar in the two groups. iCT PR were similar in OP II (mean +/- SEM: 17.2 +/- 1.5 micrograms/24 h) and controls (mean +/- SEM: 18.6 +/- 1.1 micrograms/24 h). No difference appeared between eCT PR in OP II (mean +/- SEM: 2.3 +/- 0.2 micrograms/24 h) and controls (mean +/- SEM: 3.2 +/- 0.3 pg/ml). From these data, no evidence appears that calcitonin might be one of the determinant factors in the pathogenesis of senile osteoporosis. PMID- 1627904 TI - Evaluation of worker exposure to benzene. PMID- 1627905 TI - Tooth lead concentration as an indicator for environmental lead pollution in Agra city, India. PMID- 1627903 TI - Contributions of chronological age, age at menarche and menopause and of anthropometric parameters to axial and peripheral bone densities. AB - Bone mineral density (BMD) was measured in 128 normal postmenopausal women at different skeletal sites: lumbar spine and proximal femur, using dual-energy X ray absorptiometry (DXA), and the cancellous and cortical envelopes of the distal third of radius and tibia, using precise low-dose quantitative computed tomography (QCT). Multivariate analysis included chronological age, ages related to menstrual history (menopause and menarche) and anthropometric factors, e.g. height and weight, as independent predictive variables. Weight is a much-studied predictor of bone density. At sites of high bone turnover, i.e. cancellous envelope, the effect of weight appeared overshadowed by estrogen-related parameters: age-past-menopause was the first predictor of BMD in the cancellous compartment of radius and in Ward's triangle, and the number of reproductive years was the strongest predictor of BMD in the cancellous compartment of tibia and in the spine (L2-4). This suggests that in addition to menopause, the length of menstrual life should be considered as an explanation for the variations in current bone mass in postmenopausal women. At the cortical level of radius, the effect of chronological age was predominant. At the cortical level of tibia, height and weight were the best predictors of BMD. We conclude that the influence of parameters related to menstrual history is predominant in sites with mainly cancellous tissue and that anthropometric factors constitute the best predictors of BMD in the cortical sites of weight-bearing bones. PMID- 1627906 TI - Effect of cadmium on spore germination and gametophyte development in some ferns. PMID- 1627907 TI - Comparing Cd toxicity tests with plants in monocultures and species mixtures. PMID- 1627908 TI - Effects of urban pesticide applications on nesting success of songbirds. PMID- 1627909 TI - Biochemical and histological effects of the aphicide demeton-S-methyl on house sparrows (Passer domesticus) under field conditions. PMID- 1627910 TI - Uranyl nitrate-induced glomerular basement membrane alterations in rabbits: a quantitative analysis. PMID- 1627911 TI - Airborne contaminant control in a medical examiner facility. PMID- 1627912 TI - Trihalomethanes in chlorinated drinking water of Cairo, Egypt. PMID- 1627913 TI - Organochlorine pesticide residues and PCBs in otters (Lutra lutra) from Ireland. PMID- 1627914 TI - Effect of weather variables on methyl parathion disappearance from cotton foliage. PMID- 1627915 TI - Chlorinated dioxins: volatilization from soils and bioconcentration in plant leaves. PMID- 1627916 TI - Dissipation of foliar dislodgeable residues of bendiocarb following application to azaleas. PMID- 1627917 TI - New diversity index for assessing structural alterations in aquatic communities. PMID- 1627918 TI - Pollution chemistry of the River Niger and its tributaries: characteristics of industrial waste effluents. PMID- 1627919 TI - Effect of pulp and paper effluent on a marine fish, Pseudopleuronectes americanus. PMID- 1627920 TI - Pesticide-induced atresia in ovary of a fresh water fish, Colisa lalia (Hamilton Buchanan). PMID- 1627921 TI - Acute toxicity of wood tar and dieldrin to Lebistes reticulatus (PL). PMID- 1627922 TI - Ultrastructural changes induced by diazinon and neopybuthrin in skeletal muscles of Tilapia nilotica. PMID- 1627923 TI - Accumulation and release of herbicides butachlor, thiobencarb, and chlomethoxyfen by fish, clam, and shrimp. PMID- 1627924 TI - Relationship among serum levels of luteinizing hormone, estradiol, and progesterone during follicle stimulation and results of in vitro fertilization and embryo transfer (IVF-ET). AB - Eighty-eight IVF-ET cycles were classified into four groups according to the results of IVF-ET (Group A-conceptional cycles, 10 cycles; Group B-cycles with cleaved oocytes, 58 cycles; Group C-cycles with fertilized oocytes, 9 cycles; Group D-cycles without fertilization, 11 cycles). Serum luteinizing hormone (LH), estradiol (E2), and progesterone (P) levels during follicle stimulation were studied in these groups. Patients participated in our IVF-ET program due to irreparable tubal damage. Follicle development was stimulated with a clomiphene human menopausal gonadotropin (hMG)-human chorionic gonadotropin (hCG) regimen. Group C showed a low E2 response to follicle stimulation. Groups B and D showed significantly higher serum P levels on day 0 (the day of hCG injection) than Group A (Group A, 0.73 +/- 0.11, vs Groups B and D, 1.43 +/- 0.15 and 2.17 +/- 0.42 ng/ml; P less than 0.01). The effects of serum P and LH levels on the fertilization and pregnancy rates were studied. The pregnancy rate was not affected by the serum LH level but was only 2.7% in cycles in which serum P was 1.2 ng/ml on day 0, which was significantly lower than that in cycles in which serum P was less than 1.2 ng/ml on day 0 (19.1%) (P less than 0.05). The fertilization rate was significantly lower in the cycles with higher levels of serum P and/or LH than in cycles in which serum P was less than 1.2 ng/ml and serum LH was normal (50.5 vs 78.8%; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627925 TI - Menotropin stimulation after prolonged gonadotropin releasing hormone agonist pretreatment for in vitro fertilization in patients with endometriosis. AB - Two protocols were scheduled for in vitro fertilization and embryo transfer (IVF ET) in patients with various stages of endometriosis who were resistant to conventional therapies. In the ultralong protocol (21 patients), gonadotropin releasing hormone agonist (Gn-RHa) was administered for at least 60 days prior to ovarian stimulation along with menotropin until human chorionic gonadotropin was injected. In the long protocol (11 patients), Gn-RHa was started at the midluteal phase and exogenous gonadotropin was commenced between the third and the seventh day of the menstrual cycle after pituitary suppression. The estradiol response and the number of retrieved oocytes, fertilized oocytes, cleaved oocytes, and transferred embryos were similar in both groups but the clinical pregnancy rate per transfer was superior in the ultralong protocol (67 vs 27%). The miscarriage rate was 14% (2/14) in the ultralong protocol. Prolonged Gn-RHa suppression of ovarian function before superovulation may overcome some causes of infertility in patients with endometriosis. PMID- 1627926 TI - Transplantation of fetal germ cells. AB - Oogonial stem cells are short-lived and endow the ovary with its lifetime store of follicles during fetal life. No compensatory mechanisms exist to replace germ cells that are lost for whatever reason after birth. Fetal germ cells and the abundant primordial follicles of immature animals can be successfully stored at low temperatures and transplanted to hosts to generate normal ovulatory cycles. Sterilized hosts are restored to fertility. Such results suggest that the abundant reserves of germ cells in the ovaries of human abortuses offer opportunities for treating patients whose sterility is due to afollicular ovaries uncomplicated by autoimmune disease. The prospects for this treatment depend largely on the vigilance of the recipient's immune system and public attitudes to a radical treatment, though one that promises to overcome sterility and hypoestrogenism in women with either premature menopause or gonadal dysgenesis. PMID- 1627927 TI - Endogenous luteinizing hormone surges following administration of human chorionic gonadotropin: further evidence for lack of loop feedback in humans. AB - The existence of inhibitory short- and ultrashort-loop feedback mechanisms for luteinizing hormone (LH), while documented in animals, has been questioned in humans. Since human chorionic gonadotropin (hCG) binds to LH receptors but can be distinguished from LH in immunoassays, it is possible to identify LH surges in the face of exogenously administered hCG. The present study demonstrates LH surges at midcycle in normal volunteers and in women undergoing controlled ovarian hyperstimulation, given hCG. This provides further evidence for lack of loop feedback control of LH secretion in humans. PMID- 1627928 TI - Enhancing in vitro fertilization of mouse oocytes by partial zona pellucida digestion. AB - This work was undertaken in order to evaluate the effect of partial zona digestion on fertilization in vitro of mouse oocytes and assess zona surface changes induced by the procedure. Three hundred forty-six oocytes allocated for treatment were exposed to Ham's F-10 medium supplemented with 0.5% Pronase for either 3 min (188 oocytes) or 5 min (158 oocytes); 324 oocytes served as controls. Oocyte losses incurred as a result of the procedure were small (15 oocytes; 4.3%). Control and Pronase-treated oocytes were each divided into four subgroups and inseminated with 5 x 10(5), 5 x 10(4), 5 x 10(3), or 5 x 10(2) sperm cells/ml. Fertilization was assessed 8 hr following insemination by the appearance of two pronuclei and development to the two- to four-cell stage the following day. The morphology of the zona pellucida following Pronase treatment was assessed by phase-contrast and scanning electron (SEM) microscopies performed immediately after treatment. Fertilization rate of control oocytes was 80% at a sperm concentration of 500,000/ml and gradually declined to approximately 30% at 500 cells/ml. In contrast, treated oocytes inseminated with 500 sperm cells/ml demonstrated a normal rate of fertilization. At this low sperm concentration the longer Pronase treatment was significantly (P less than 0.05) more efficient in enhancing fertilization (69 and 88% for 3 and 5 min of Pronase treatment, respectively). Polyspermic fertilization was not observed in any of the subgroups. Phase-contrast microscopic examination of oocytes at the time of Pronase treatment showed an initial swelling of the zona pellucida for 30-60 sec with a time-dependent increase in its transparency. PMID- 1627929 TI - Effects of human serum on rat cumulus-oocyte complex functions in vitro: oocyte activation and endocrine secretions. AB - Secretion of hormones and oocyte meiotic events were assessed following in vitro culture of ovulated rat cumulus-oocyte complexes (COCs) in media containing different types of human serum. Both toxic and nontoxic (determined by mouse embryo test) samples of fetal cord or adult female serum were utilized for these experiments. After short-term culture (4.5 hr), with or without COCs, medium containing 10% serum was collected and analyzed for its content of estradiol, progesterone, and prostaglandin E (PGE), and oocytes were cytologically evaluated for spontaneous activation (second polar-body extrusion). Activation of oocytes occurred in all media tested. Steroids (progesterone and estradiol) levels were markedly elevated in culture medium containing cord serum as compared to medium containing adult female serum. The progesterone content of culture medium decreased after incubation of COCs with cord serum and increased when incubated with adult female serum. Little or no prostaglandin was detected in any control media. However, COCs secreted prostaglandin during culture in all media. COCs secreted estradiol when cultured in medium containing cord but not adult female serum. Results demonstrate that two types of serum utilized for in vitro culture of COCs varied markedly in their hormone content and differentially affected the secretion of hormones by COCs during culture. The results are discussed in relation to the success of IVF procedures. PMID- 1627930 TI - The effects of cooling mouse oocytes. AB - The effects of cooling and warming on meiotic spindles of mouse oocytes have been assessed by transmission electron microscopy. Intact cumulus-oocyte complexes were immediately cooled from 37 to 15, 4, 0, and -7 degrees C (seeding temperature) for 15 min in a programmed biological freezer and fixed at these temperatures. Other complexes, cooled to these temperatures, were rapidly warmed to 37 degrees C and incubated for 2 hr before fixation at 37 degrees C. Of 334 oocytes assessed at various temperatures, at least 100 were examined for metaphase II spindles. Spindle microtubules completely disappear at 0 and -7 degrees C, while complete or partial depolymerization of microtubules was observed at 4 degrees C. Cooling to 15 degrees C did not cause major disruptions of spindle structure in most oocytes. Chromosomes tended to rotate or clump at lower temperatures but chromosome scatter outside the spindle zone was rarely observed. Centrosomal material was fragmented at 4 degrees C and occasionally at 15 degrees C and was not evident at the spindle poles at 0 and -7 degrees C. Kinetochores were seen at all temperatures. Spindle structure was evidently restored in the majority of oocytes on rewarming at 37 degrees C. Changes in the ooplasm induced by cooling were elongation and disruption of vesicular smooth endoplasmic reticulum, especially between lipid globules and disappearance of fibrillar inclusions. Cortical granule exocytosis was not observed on cooling, while microfilaments were intact. Swelling of membranous organelles was also observed in cumulus cells. Most of the cytoplasmic changes were also reversed on rewarming. The response of mouse oocytes to cooling is compared to that of human oocytes, reported previously. PMID- 1627931 TI - In vitro preimplantation mouse embryo development with incubation temperatures of 37 and 39 degrees C. AB - Embryos from two strains of mice were used to assess the effect of incubation temperature on pronuclear and two-cell development to the morula/blastocyst (M/B) stage. Embryos from B6D2F2 and B6SJLF1 strains were cultured in medium M16 at either 37 or 39 degrees C until 120 hr post human chorionic gonadotropin (hCG) or 0, 24, or 48 hr at 37 degrees C and the remaining time at 39 degrees C. Overall M/B development for pronuclear embryos was 0.6, 0, 32.3, and 52.4% for 0-96, 24 72, 48-48, and 96-0 hr at 37 and 39 degrees C, respectively. Only 0-96 and 24-72 hr at 37 and 39 degrees C were not different (P greater than 0.10). Overall M/B development for two-cell embryos was 48.1, 78.1, and 98.0% for 0-72, 24-48, and 72-0 hr at 37 and 39 degrees C, respectively. Percentage development at each time was different (P less than .01) for each category. Additionally, the number of nuclei for morulae and blastocysts tended to be higher for embryos initiating culture at the two-cell stage compared to pronuclear embryos. The first cell cycle was most dramatically affected by a 2 degrees C increase in incubator temperature. More advanced embryos can tolerate slight increases in incubator temperature more readily than pronuclear embryos. PMID- 1627932 TI - The effect of caffeine on the ability of spermatozoa to fertilize mature human oocytes. AB - Although caffeine has been reported to enhance spermatozoon motility as well as fertilizing ability, its use in clinical practice has remained sparse. We report here the results carried out to assess the effect of exposing normal human spermatozoa to different concentrations of caffeine on their motility, their ability to fertilize oocytes, and the subsequent development of resulting embryos. Mature human oocytes were inseminated with spermatozoa washed and capacitated in 1.25, 2.5, and 5 mM caffeine. The fertilization rates were compared with control oocytes inseminated with untreated spermatozoa. While caffeine was observed to improve significantly various motility parameters in a dose-dependent manner, it did not lead to an improvement in the fertilization rates. At the highest concentration, 5 mM, it adversely affected the fertilization rate: 38%, compared with 78% in controls. Embryonic development was also observed to be retarded at the lower concentrations, while it was virtually inhibited in the 5 mM concentration group. Our results suggest that while a definite improvement in motility may occur when spermatozoa are exposed to caffeine, this improvement did not translate into enhanced fertilizing ability and subsequent embryonic development. We are therefore of the opinion that the use of caffeine as a spermatozoon motility enhancer requires further studies prior to wider clinical use in assisted pregnancy programs. PMID- 1627934 TI - Successful parents of in vitro fertilization (IVF): the social repercussions. AB - A matched comparison was made of 157 parents of preschool twins conceived by one of the following: in vitro fertilization (IVF), infertility workup combined with infertility drug treatment, or spontaneously. The Interview Schedule for Social Interaction was used to examine systematically a comprehensive range of social relationships and the asymmetries therein. Overall, IVF parents reported having deficient social relationships compared with non-IVF parents, and this deficiency was both in size and in affective quality of their available relationships. As anticipated, mothers reported less adequate and available social relationships when compared with their spouses. In the event of a significant finding, mothers from the three groups always had lower mean scores than the fathers. The finding of the extent to which IVF parents were not as socially integrated, compared with the other families of preschool twins, highlights the need to strengthen through mutual aid IVF parents' social networks. The data also suggest the need for ongoing patient care by IVF teams and for support groups to be established exclusively for IVF parents of twins. PMID- 1627933 TI - Psychological and hormonal changes in the course of in vitro fertilization. AB - This study was designed to investigate concurrently the psychological and hormonal changes at three critical points during in vitro fertilization (IVF) treatment. One hundred thirteen couples suffering from mechanical and unexplained infertility participated in the study and 23 of them conceived. Psychological evaluation included background questionnaires, Lubin's Depression Adjective Check List, and Spielberger's State Trait Anxiety inventory. Cortisol and prolactin levels were estimated by radioimmunoassay. The results showed that patients' anxiety and depression scores were significantly higher than the population norm. Psychological test scores and hormonal levels showed a similar pattern of change, increasing on oocyte retrieval day, decreasing on embryo transfer day, and rising again on pregnancy test day. Differences between these phases were generally significant. Differences in parameters' means between conceiving (C) and nonconceiving (NC) women were generally not significant. However, correlations between psychological measures and hormonal levels showed a clear disparity between C and NC women in the last phase. Whereas significant negative correlations were found in C patients, no relationship was found in NC patients. The findings suggest that success in IVF treatment may depend, in part, on differential modes of coping with anxiety and depression, involving hormonal or endorphin mediation. PMID- 1627936 TI - Genetics update: infertility due to a point mutation. PMID- 1627935 TI - Impaired human embryo development in Earle's culture medium compared to Ham's F10. PMID- 1627937 TI - Attitudes toward embryo research. PMID- 1627938 TI - Controversies and opinions in clinical microsurgical fertilization. PMID- 1627939 TI - Subzonal sperm insertion and the frequency of gamete fusion. AB - The subzonal sperm insertion technique was applied to assess the potential of motile human spermatozoa to form pronuclei. In 184 mature human oocytes, subzonal sperm insertion was used as the primary mode of insemination in cases with abnormal semen analyses. Oocytes (n = 131) that failed to fertilize in vitro in cases with normal semen profiles were also micromanipulated for secondary insemination. The frequency of sperm fusion, expressed as a percentage, was defined as the total number of male pronuclei formed divided by the total number of spermatozoa inserted subzonally. Our results indicate that 37% of spermatozoa from men with normal semen are able to fuse with the oolemma and decondense within the ooplasm, when placed in the perivitelline space of the oocyte. Excluding the oocytes that appeared morphologically abnormal (presence of cytoplasmic inclusions such as refractile bodies within the ooplasm), the frequency of sperm fusion increased to nearly 60%. Moreover, 14% of subzonally inserted spermatozoa from men with abnormal semen analyses demonstrated an ability to form a pronucleus. The incidence of polyspermy was high, ranging from 30 to 80% in the different groups studied. It is therefore concluded that the human oolemma provides little protection against multiple sperm fusion and that the frequency of gamete fusion is unexpectedly high, even when the spermatozoa are derived from infertile men. PMID- 1627940 TI - [Relation between traditional Chinese medicine differentiation of syndromes and HBV antigen, HBV DNA in serum and liver tissues and pathological changes in chronic hepatitis B]. AB - TCM differentiation of syndrome in 131 cases of chronic hepatitis B has been studied with molecular-biological and immuno-histological techniques. The results showed that 94.6% cases of Gan-Yu Pi-Xu (stagnancy in the liver leading to diminished function of the spleen) type belonged to chronic persistent hepatitis (CPH), whose coincidence rate of pathology of the liver biopsies with CPH was 69.2%; the positive rate of HBeAg and/or HBV DNA in sera was 61.5%, and the positive rates of HBsAg and HBV DNA in liver tissues were 69.2% (of which 44.4% appeared diffuse pattern morphologically) and 33.3% respectively. 75.5% cases of Gan-Shen Yin-Xu (deficiency of Yin of the liver and kidney) type belonged to chronic active hepatitis (CAH) and 88.5% of the cases were pathologically described as CAH, the positive rates of HBeAg and/or HBV DNA in serum and HBsAg in liver tissues were all 80.8%, among which the diffuse pattern of HBsAg accounted for 85.7%, which was higher than that in Gan-Yu Pi-Xu type (P less than 0.05), the positive rates of HBcAg and HBV DNA in liver tissues were 34.6% (of which 55.6% appeared cytoplasmic pattern) and 63.2% respectively, which was higher than that in Gan-Yu Pi-Xu type (P less than 0.05). 75.0% cases of Qi-Zhi Xue-Yu (stagnation of vital energy and stasis of blood) type belonged to CAH with early state cirrhosis, its pathological changes in liver tissues were obvious, replication levels of HBV corresponded to the cases of Gan-Yu.Pi-Xu type. PMID- 1627941 TI - [Characteristics of traditional Chinese medicine syndromes in both spontaneous and variant angina. An analysis of 21 cases]. AB - An analysis of TCM syndromes is reported in 21 cases with both spontaneous and variant angina as compared with 147 cases with effort angina. The results showed that 3 characteristic features were present, which were as follows: the Biao-Shi syndrome of cold condensation was more than that of the control group in ratio of 42.86% to 3.40%; the Ben-Xu syndrome of Yang deficiency was more and that of Qi deficiency less than those in the control group, and they were in ratio of 33.33% to 6.12% and 33.33% to 72.11% respectively. An absolute reduction of blood supply resulted from coronary spontaneous spasm in both spontaneous and variant angina causes severe chest pain during attacks as a cold condensation type. Hyperfunction of parasympathetic nerves often occurring in coronary heart disease with Yang deficiency is liable to vasoconstriction of the large coronary arteries leading to episodes of both spontaneous and variant angina. The presence of less Qi deficiency type may be related to the less impairment of cardiac function resulted from the short course in these cases and only relatively mild state of an illness, even no marked lesion in coronary arteries in a part of patients with both spontaneous and variant angina. No significant difference in TCM syndromes occurred between spontaneous and variant angina. Both Yang and Yin deficiency, as the Ben-Xu syndromes, were more present in angina of cold condensation type.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1627942 TI - [Treatment of IgA nephropathy by integrated traditional and Western medicine]. AB - 45 cases of IgA nephropathy were confirmed by renal biopsy and were divided into 2 groups, the integrated traditional and western medicine (TCM-WM) therapeutic group and the western medicine (WM) therapeutic group. The WM group was treated by conventional western medicine (persantin, vitamin B co.), and the TCM-WM group was treated by the same western medicine plus differential symptomatic treatment with decoction of Chinese crude herbs. In this paper, most patients (30 cases) were present as deficiency of Yin of the Liver and Kidney type, and were treated by Qiju Dihuang pill plus Erzhi pill. All types in TCM-WM group were also used herbs of promoting blood circulation and remove blood stasis in almost every case. After 6 months of such treatment, the total effective rate of TCM-WM group and the WM group were 86.4% and 13.0% respectively. There was very significant difference (P less than 0.01) between them. The results showed that the curative effect of the TCM-WM group was much superior than WM alone for the treatment of IgA nephropathy. PMID- 1627943 TI - [Effect on anti-aging and treating yang deficiency of kidney with huanshao dan capsules. A clinical report of 309 cases]. AB - In this study, with various dosages of huanshao dan capsules, an old Chinese medicine formula, the authors treated the patients with Yang-deficiency of kidney for 1.5-3 months and compared the effects of huanshao dan with those of watered pills and placebo. The analyses of Ridit's showed not only the scores of symptoms of the great-dose huanshao dan group (group 2), the great-dose watered pill group (group 3), the small-dose watered pill group (group 4) and but even the short treating course group (group 5) were remarkably improved after treatment (P less than 0.001, P less than 0.01); but the group 6 have not any difference after treatment. However, the functions of liver and kidney, the level of cholesterol, the concentration of blood sugar, blood pressure and heart rate remained the same after treatment. The scores of the ability of prompt memory as well as serum lipid peroxide, serum adrenocortical hormone, cellular immunological function, index of glycoprotein and T3, T4 had similar changes. Our data suggested that both huanshao dan and watered pills were beneficial for anti-aging process and there was no noticeable difference between the two drugs. PMID- 1627945 TI - [Initial clinical application of cardiac pacing needle for emergency cardiac pacing]. AB - This paper deal with the newly designed cardiac pacing needle which is used as an electrode in temporary cardiac pacing. Animal experiment has shown that in emergency life-saving this needle was functional and reliable. This also has been identified by clinical application. By utilizing the needle, the authors have successfully saved three patients' life threatened by sudden death. Using this needle to pace the heart is simple, swift, immediate and has less side effect. It is specially fit for grassroot medical units to develop emergency cardiac pacing. PMID- 1627944 TI - [A clinical study of the effect of wuzi yanzong solution in retarding aging process]. AB - Eighty men ranging from 60 to 80 years old were selected, in whom no disease was found through a thorough check-up except for some senility manifestation diagnosed as deficiency of the kidney. They were randomly divided into two groups, wuzi yanzong solution (WYS) being administered in 50 cases and placebo in 30. After 5 weeks' treatment, symptoms such as hypomnsis, tinnitus, and aching of the back and legs, dribbling after urinary voiding, and nocturia were remarkably improved in the WYS group, but they remained as before in the placebo group. Before the treatment, plasma lipid peroxide (LPO), erythrocyte superoxide dismutase (SOD), blood glutathione peroxidase (GSH-Px), serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), plasma testosterone (T) and estradiol (E2) levels were determined. In comparison with the results obtained in 33 young men in their twenties, LPO, FSH, LH level and E2/T ratio in the aged were greatly elevated, and SOD, GSH-Px and T markedly lowered. After the treatment, there was remarkable reduction of LPO and E2/T, and increase of SOD and T in the WYS group, but no significant change in the placebo group. The above results not only indicate the beneficial effect of WYS in retarding the aging process, but also suggest the possible mechanism of reducing the peroxidation of fatty acids by enhancing the antioxidant enzymes to inhibit free radical activity. PMID- 1627946 TI - [Effects of xiang sha liu jun zi tang on gastric and intestinal functions in animals]. PMID- 1627947 TI - [Treatment of cholelithiasis in China--discharge, dissolution, crushing and removal]. PMID- 1627948 TI - [Current status of prevention and treatment of traditional Chinese medicine for ototoxic effect of streptomycin]. PMID- 1627949 TI - Lymphocyte subpopulation number and function in infancy. AB - Normal values for percentages of lymphocyte subpopulations and functional responses to mitogen stimulation in infancy are not well established. In the present study, lymphocyte subpopulations were examined in umbilical cord blood samples and in peripheral blood samples drawn before 7 and 24 months of age (mean age 10.4 months) from a healthy population of infants born in Tucson, Arizona. Results indicate significant increases occurred from birth to later infancy in the percentages of total T cells (CD3), T-cell subsets (CD4, CD8) and B cells (CD20). The CD4/CD8 ratio and the functional responses to ConA and PWM mitogens significantly decreased from birth to later infancy. PHA responsiveness did not show a significant change. Results from cross-sectional analyses (n = 271) were supported in a smaller longitudinal subset (n = 37). There were no detectable ethnic- or gender-related differences in cord blood or samples obtained in later infancy. The normal values established in this study will be useful in studies of immune-system maturation and in the clinical evaluation of newborns, infants, and toddlers suspected of either acquired or congenital immune-deficiency states. PMID- 1627950 TI - Transient developmental expression of IgY and secretory component like protein in the gut of the axolotl (Ambystoma mexicanum). AB - We previously reported that a primitive vertebrate, the Mexican axolotl (Amphibian, Urodela) synthesizes two classes of immunoglobulins. IgM are present in serum early in the development, and represent the bulk of specific antibody synthesis after an antigenic challenge. IgY occur in the serum later during the development, and are relatively insensitive to immunization. We demonstrate in the present work, using immunofluorescence with specific Mabs, that IgY are expressed in the gut epithelium, as secretory molecules. Secretory IgY are well expressed in the stomach and intestinal mucosae of young animals from 1 month after hatching to the seventh month. Thereafter, IgY progressively disappear from the gut and become readily detectable in the serum of 9-month-old preadult immunologically mature animals. Axolotl IgY are closely associated in the gut to secretory component-like (SC) molecules that are well-recognized by antisera to the SC of different mammalian species. This is the first description, in a primitive tetrapode, of an immunoglobulin class that could be the physiological counterpart of mammalian IgA. PMID- 1627951 TI - Thymic involution in viable motheaten (me(v)) mice is associated with a loss of intrathymic precursor activity. AB - Mice homozygous for the viable motheaten (me(v)) allele manifest abnormalities in thymocytopoiesis, are severely immunodeficient, and develop autoimmune disorders early in life. Premature thymic involution occurs in me(v)/me(v) mice, and their bone marrow prothymocytes are unable to repopulate the thymus of adoptive recipients following intravenous (i.v.) transfer. However, analysis of thymocytopoiesis following intrathymic (i.t.) adoptive transfer of bone marrow from me(v)/me(v) mice demonstrates the presence of normal numbers of prothymocytes. To investigate intrathymic development in me(v)/me(v) mice, we determined intrathymic precursor cell number and activity. Dual labeling analyses showed that an involuted me(v)/me(v) thymus is relatively enriched (fivefold) in CD4-CD8- thymocytes (intrathymic precursor phenotype) compared with wild-type (+/+) thymus. However, thymocytes from me(v)/me(v) mice were deficient in precursor activity when adoptively transferred i.t. into irradiated recipients. Thymocytes recovered from the involuted thymus of aged or steroid-treated normal mice also displayed reduced precursor activity. However, the phenotypic profile of thymocyte subsets from steroid-treated mice was enriched in single positive cells (mature phenotype) and was distinctly different from the subset distribution of thymocytes in me(v)/me(v) and aged mice. These results suggest that intrathymic precursor activity in me(v)/me(v) mice is decreased, and may be reflective of decreased prothymocyte seeding to the thymus in vivo. In addition, the results suggest that the thymic involution in me(v)/me(v) mice is not due solely to effects of corticosteroids. PMID- 1627952 TI - T-cell-specific membrane antigens in the Mexican axolotl (urodele amphibian). AB - Comparative analysis of SDS-PAGE patterns of axolotl spleen cells membrane detergent lysates showed important discrepancies between control and thymectomized animals. Among these, a 38-kD protein band, which appeared as a major protein in controls, was not or poorly expressed after thymectomy. A rabbit antiserum (L12) raised against the 38-kD eluted band labeled in indirect immunofluorescence 80-86% of thymocytes and 40-46% of mIg- lymphoid cells in the spleen. The anti-38-kD antibodies stained in Western blotting two antigenically related polypeptides of 38- and 36-kD on splenocyte membrane lysates. Two dimensional NEPHGE-PAGE analysis indicated that the anti-38-kD antibodies reacted in the spleen with several gathered spots in the 7.8-8.2 pI range, corresponding to 38-36-kD microheterogeneous polypeptides. Most of these spots are not further expressed in thymectomized animals. These results support evidence that the 38-kD surface antigens can be considered as specific surface markers of the axolotl thymus-derived lymphocytes. PMID- 1627953 TI - Neuropsychiatry and homosexuality: on the need for biopsychosocial interactionism. PMID- 1627954 TI - Assessment of bromocriptine intervention for the treatment of frontal lobe syndrome: a case study. PMID- 1627955 TI - A psychiatrist replies to Yudofsky's "Psychoanalysis, psychopharmacology, and the influence of neuropsychiatry". PMID- 1627956 TI - Sometimes when you hear hoofbeats ... two cases of inherited metabolic diseases with initial presentation of psychiatric symptoms. PMID- 1627957 TI - Incidence of AIDS dementia in a two-year follow-up of AIDS and ARC patients on an initial phase II AZT placebo-controlled study: San Diego cohort. AB - In a prospective study to determine the incidence of clinical dementia in patients with AIDS and ARC, 29 men and 3 women, 19 with ARC and 13 with AIDS, were examined neurologically and neuropsychologically every 6 months for 2 years during a placebo-controlled zidovudine (AZT) licensing trial. Most received two MRI brain scans. Although no patient was clinically demented at baseline, 9 (28%) developed dementia during the 2 years. Progression to dementia was associated with neuropsychological deterioration and with worsening on MRI during a preceding 6-month period, but not with baseline treatment group assignment. The results suggest that patients at CDC Stage IV who do not receive antiretroviral treatment earlier in their illness may develop clinical dementia at an annual rate of about 14%. PMID- 1627958 TI - Neuropsychological and neurological manifestations of HIV-1 dementia in drug users. AB - The cognitive and motor deficits associated with human immunodeficiency virus-1 (HIV-1) infection have been studied using neurological examination and neuropsychological tests. However, drug users with HIV-1 infection generally have been excluded from such studies. Forty-four well-characterized drug users stratified by Centers for Disease Control staging were administered a standardized neurological examination and a battery of neuropsychological tests under single-blind conditions designed to minimize the acute effects of psychoactive substances. The results of the blind neurological examination were consistent with the previously ascertained clinical staging of HIV-1 infection. The pattern of neuropsychological deficits across HIV-1 states was similar to those found in cohorts of homosexual men. PMID- 1627959 TI - Staining intensity of brain iron in patients with schizophrenia: a postmortem study. AB - Evidence derived from both pharmacological and postmortem studies suggests that a disturbance of brain iron metabolism is involved in the pathophysiology of schizophrenia; i.e., the distribution of iron parallels that of dopamine, and variations in its brain concentration selectively modulate the binding affinity of the dopaminergic (D2) receptor. In the present study the authors examined the staining intensity of brain iron in postmortem specimens of 9 schizophrenic (SC) patients and 17 age-matched controls. Coronal sections were stained with the Perls's technique, photographed, and then studied using a computerized image analysis system. Optical density measurements were taken from the caudate nucleus, putamen, globus pallidus, and substantia nigra. This study revealed significant differences between groups only for the staining intensity of iron in the caudate nucleus (P less than 0.005). A review of the literature suggests that this finding may be the result of neuroleptic therapy and not a primary pathological feature of schizophrenia. PMID- 1627960 TI - Violent visual hallucinations and aggression in frontal lobe dysfunction: clinical manifestations of deep orbitofrontal foci. AB - Three patients from different racial, social, and economic backgrounds were studied because of sudden intrusive thoughts: visions or intrusions of threatening scenes--violent, aggressive, and sometimes horrifying--that lasted from seconds to minutes. Apart from the association with intense anxiety, fear, and aggression, there was no association with oculomotor, motor, sensory, or autonomic dysfunction or altered conscious state. Patients had abnormal intermittent discharges that arose from frontal areas and probably did not spread further. Carbamazepine was useful in two cases. The authors suggest that violent, brief hallucinations with no other epileptic sign may be manifestations of frontal lobe seizures. PMID- 1627961 TI - Hypothalamic lesions and intermittent explosive disorder. AB - The authors present two cases of patients with craniopharyngiomas who meet the DSM-III-R criteria for intermittent explosive disorder. Episodes of rage developed before and/or after surgery for removal of the craniopharyngioma. Magnetic resonance imaging revealed hypothalamic-hypophyseal involvement. It is suggested that hypothalamic lesions played a major role in the development of aggressive behavior in both cases. PMID- 1627963 TI - Alzheimer and Kraepelin describe Binswanger's disease. PMID- 1627962 TI - Organic mood disorder associated with the HAIR-AN syndrome. AB - The HAIR-AN syndrome is characterized by hyperandrogenism, insulin resistance, and acanthosis nigricans. The authors report the first case of an organic mood disorder associated with this condition that improved markedly in response to ovarian suppression with oral contraceptives. The proposed pathophysiology of this syndrome is also discussed. PMID- 1627964 TI - Plasma beta-endorphin levels in post-traumatic stress disorder: a preliminary report on response to exercise-induced stress. AB - Post-traumatic stress disorder (PTSD) may be associated with changes in endogenous opioid peptide function. To test this hypothesis, 10 male Vietnam combat veterans with PTSD and 8 age-matched male controls underwent a standard grade-incremented exercise treadmill stress test. Plasma beta-endorphin measurements were obtained at rest and following maximal exercise. Resting plasma beta-endorphin levels were comparable between groups. Post-exercise plasma beta endorphin levels were significantly higher than resting levels in the PTSD patients only (P less than 0.05). These pilot data suggest a differential alteration in plasma beta-endorphin response to exercise in PTSD. PMID- 1627965 TI - Dysnomia in the differential diagnosis of major depression, depression-related cognitive dysfunction, and dementia. AB - This study examined naming abilities in three groups of older adults with: I) major depression alone, II) major depression with reversible cognitive dysfunction, and III) dementia with depression. Groups I and II differed significantly from dementia patients in total correct responses to a visual confrontation naming task (Boston Naming Test). Qualitative aspects of naming, specifically types of errors characterizing each patient group, were examined, but no statistically significant differences among groups were observed. The results support the contention that the presence of dysnomia may be useful in discriminating cognitive abnormalities secondary to dementia from cognitive dysfunction associated with depression. PMID- 1627966 TI - Open trial of intravenous clomipramine in five treatment-refractory patients with obsessive-compulsive disorder. AB - In a preliminary trial, five oral-clomipramine-refractory patients with obsessive compulsive disorder (OCD) were treated openly with 14 intravenous clomipramine infusions each. Using standardized assessments, three patients were rated as much improved, one as unchanged, and one as minimally improved. Statistically significant improvements were noted on both the Yale-Brown Obsessive Compulsive Scale and the NIMH Global OCD scores. No patient discontinued treatment because of side effects. Although the results are provocative in that three of five patients were much improved at the end of the protocol, conclusions about preferential efficacy for the intravenous route must await a placebo-controlled trial. PMID- 1627967 TI - Contingent tolerance and reresponse to carbamazepine: a case study in a patient with trigeminal neuralgia and bipolar disorder. AB - This retrospective single-case study demonstrates the development of tolerance and reresponse to carbamazepine in a patient with coexisting trigeminal neuralgia and manic-depressive illness. After an initial positive response, tolerance to the antinociceptive and psychotropic effects of carbamazepine appeared during treatment, despite increasing doses. As in preclinical studies of contingent tolerance, periods of carbamazepine discontinuation were associated with reresponse following reinstitution. These are the first clinical data interpreted in a contingent tolerance formulation with reresponse following a medication-free interval. Controlled and prospective studies are needed of the reliability and the pathophysiological and therapeutic implications of this phenomenon. PMID- 1627968 TI - Failure of buspirone and verapamil to improve spasmodic torticollis. AB - The effects of buspirone and verapamil on spasmodic torticollis were investigated in two double-blind, placebo-controlled crossover studies. Buspirone was given in doses of 20-100 mg/day for 4 weeks to 14 patients; verapamil was given in doses of 40-100 mg/day for 3 weeks to 8 patients. Neither drug improved symptoms of the movement disorder (posture, motility, rigidity, tremor), pain, perceived stress, or mood, either in the whole group or in any individual patient. PMID- 1627970 TI - Diagnostic tests and information theory. AB - Our previous article showed that the discriminating properties of most diagnostic tests in medicine can be characterized by assuming that tests separate disordered and nondisordered individuals into two overlapping, normal distributions with different means and standard deviations. In this article, we explore the relationship between this way of describing diagnostic tests and the reason that clinicians use them: to gain information about their patients and to reduce diagnostic uncertainty. PMID- 1627969 TI - The application of the Screening Cerebral Assessment of Neppe (BROCAS SCAN) to a neuropsychiatric population. AB - Assessments of higher cortical functioning are often neglected in patients with possible coarse neurobehavioral psychiatric disease, such as dementia, stroke, or focal cerebral lesions. When performed, the short Folstein Mini-Mental State Exam (MMSE) is typically used. The authors' research on 45 neuropsychiatric patients compared the MMSE with a new 20-30-minute bedside examination, the Screening Cerebral Assessment of Neppe (BROCAS SCAN). This screens 10 areas: recall, recognition, orientation, organization of thought, concentration, calculation, agnosia, apraxia, speech, and sensory-motor-reflex phenomena. The BROCAS SCAN (total) correlated extremely well with neuropsychiatric prediction, MRI changes, and neuropsychological testing, and distinguished diagnoses, demonstrating construct and face validity. It also accounted for a larger proportion of variance than the MMSE in correlating with these parameters and was more sensitive in mildly cognitive impaired patients. The briefer first section of the BROCAS SCAN, the core SCAN, also showed statistically relevant relationships to age, diagnosis, MRI, and neuropsychiatric prediction. PMID- 1627971 TI - Is schizophrenia a neurological disorder? PMID- 1627973 TI - Reliability, validity, and clinical correlates of apathy in Parkinson's disease. AB - The authors examined a consecutive series of 50 patients for the presence of apathy, depression, anxiety, and neuropsychological deficits using a neuropsychological battery that included a recently designed apathy scale. This scale was found to be reliable and valid in the diagnosis of apathy in patients with PD. Of patients in the study, 12% showed apathy as their primary psychiatric problem, and 30% were both apathetic and depressed. Patients with apathy (with or without depression), showed significantly more deficits in both tasks of verbal memory and time-dependent tasks. Results suggest that apathy is a frequent finding in PD, is significantly associated with specific cognitive impairments, and may have a different mechanism than depression. PMID- 1627972 TI - Image processing for the study of brain structure and function: problems and programs. AB - Fundamental problems in the analysis of functional and structural imaging data include data transport, boundary identification (including manual tracing, edge detection, and tissue segmentation), volume estimation, three-dimensional reconstruction and display, surface and volume rendering, shape analysis, and image overlay. These problems require that research investigators have access to suitable methods of image analysis, implemented on a set of software programs, in order to conduct neuroimaging research. The authors describe a group of software programs designed to provide a comprehensive solution for these problems. PMID- 1627974 TI - Electroconvulsive therapy for post-stroke depressed geriatric patients. AB - Medical records were retrospectively reviewed for 20 medically ill geriatric patients who received electroconvulsive therapy (ECT) for post-stroke depression from January 1982 to January 1991 at Massachusetts General Hospital. Of the 19 patients (95%) who improved with ECT, 7 patients (37%) suffered relapses despite maintenance anti-depressant medications. Relapses typically developed approximately 4 months after ECT. Five patients (23%) developed ECT-related medical complications. Three patients (15%) developed transient interictal confusion or amnesia. No patient experienced an exacerbation of preexisting neurologic deficits. These findings indicate that ECT is a generally well tolerated and effective treatment for depressed, medically ill post-stroke geriatric patients. PMID- 1627975 TI - Multiple sclerosis and ECT: possible value of gadolinium-enhanced magnetic resonance scans for identifying high-risk patients. AB - Electroconvulsive therapy (ECT) has been used effectively in treating depressed patients with multiple sclerosis (MS). However, several reports have observed that some patients with MS may suffer neurological deterioration during ECT. The authors describe the outcomes of 3 depressed patients with MS who were treated with ECT. Consistent with previous works, ECT effectively treated the psychiatric symptoms; however, 1 patient deteriorated neurologically during ECT. The brain MRI findings and clinical courses of all 3 patients are discussed, along with the possible value of gadolinium-contrast MRI scans for identifying high-risk patients. PMID- 1627976 TI - Magnetic resonance imaging correlates of neuropsychological impairment in multiple sclerosis. AB - The authors examined whether specific neuropsychological abnormalities in multiple sclerosis (MS) are associated with focal lesion areas detected by MRI. Lesion area, regardless of distribution, correlated with performance on the vast majority of neuropsychological procedures. No significant difference appeared between groups with normal/mild and moderate overall cognitive impairment on any of the MRI measures. However, patients with severe cognitive impairment had greater lesion area, regardless of location, and had significant atrophy of the corpus callosum compared with the other two groups. These results suggest that severe atrophy of the corpus callosum reflects global disease and provides a relatively focal morphological marker of severe cognitive impairment in MS. PMID- 1627977 TI - Regional cerebral glucose utilization in chronic organic mental disorders associated with alcoholism. AB - Localized cerebral utilization rates for glucose (CMRglu) were determined in 10 detoxified patients with alcoholic organic mental disorders and in 7 age equivalent normal volunteers using [18F]2-fluoro-2-deoxyglucose positron emission tomography. Although gray and white matter CMRglu were not significantly different, normalized CMRglu was increased in the left cerebellar and parietal cortical regions and decreased in the right posterior white matter and anterior temporal regions of alcoholic patients, and the pattern of regional CMRglu differed between the two groups. The results suggest functional disruption of right-sided and frontal brain regions and hyperactivity of cerebellar-cortical connections in alcoholic chronic organic mental disorders. PMID- 1627978 TI - Magnetic resonance imaging of white matter lesions in HIV infection. AB - Previous studies of the frequency of high-signal lesions in human immunodeficiency virus (HIV) infection have had methodological weaknesses regarding lack of control groups, differing machine strengths, and biased subject selection. To obtain a more accurate estimate of prevalence, MRI scans were performed on 243 HIV-positive and HIV-negative homosexual or bisexual men with no history of intravenous drug use. Axial T2-weighted (long TR/TE, spin-echo) MRI scans were rated blindly for presence of focal white matter high-signal lesions. Incidence of hyperintensities was low in all groups, although slightly higher in patients with AIDS, and was not associated with neuropsychological performance. The lower incidence of hyperintensities appears to relate to elimination of methodological problems in previous studies. PMID- 1627979 TI - Comparison of two cognitive screening measures for efficacy in differentiating dementia from depression in a geriatric inpatient population. AB - The Folstein Mini-Mental State Examination (MMSE) and dementia screening measures developed by Benton (temporal orientation, oral word association, and visual reconstruction tasks) were compared for diagnostic efficacy with geriatric inpatients manifesting depression without dementia or mild or moderate dementias complicated by depression. Both instruments showed generally acceptable differentiation between dementia and depression-only cases overall. The MMSE was less sensitive in identifying mild and moderate multi-infarct dementias but showed better specificity than the Benton measures. The degree and type of dementia and the associated risk of classification error were found to be important factors in the choice of screening instruments. PMID- 1627980 TI - Neuroleptic malignant syndrome and preexisting brain damage. AB - A case of neuroleptic malignant syndrome (NMS) is described in a congenitally brain-damaged deaf patient. The literature suggests that NMS in patients with organic brain syndrome is induced by a reduction of marginal stores of dopamine in the hypothalamus and basal ganglia resulting from dopamine-blocking activity of neuroleptics, even at conventionally low doses. Brain-damaged patients should be recognized as being at higher risk of developing NMS. PMID- 1627981 TI - Depression during treatment with beta-blockers: results from a double-blind placebo-controlled study. AB - Depressive symptoms were rated during a double-blind placebo-controlled trial of nadolol for chronic aggression. Depressive symptoms were not significantly different in nadolol and placebo groups during any phase of the drug trial. PMID- 1627982 TI - Aggressive behavior following exposure to cholinesterase inhibitors. AB - The authors report four instances of significant, essentially unprovoked aggressive behavior, including two homicides, following exposure to cholinesterase inhibitors. No subject had a history of violent behavior, antisocial personality, or major psychiatric or neurologic disorder. After anticholinesterase exposure ceased, all showed sincere remorse for their actions, and none has since engaged in aggressive or psychopathologic behavior. Well controlled experimentation in animals suggests that enhanced activation of hypothalamic cholinergic receptors may underlie aggressive behavior in humans exposed to cholinesterase inhibitors. A relationship between cholinesterase inhibitors and aggression has important implications for public health, raising the possibility of unappreciated neurotoxic influences on behavior. PMID- 1627983 TI - Anticholinergic delirium caused by topical homatropine ophthalmologic solution: confirmation by anticholinergic radioreceptor assay in two cases. AB - The authors report two patients with prolonged metabolic delirium presumably initiated by systemic absorption of homatropine from a topical ophthalmologic solution. Anticholinergic toxicity was confirmed by muscarinic radioreceptor assay in both cases and by quantitative EEG in one case. PMID- 1627984 TI - Comparing diagnostic tests using information theory: the INFO-ROC technique. AB - We continue our examination of diagnostic tests that are used to assign individuals to one of two mutually exclusive categories, those having or not having a particular disorder. Our last article showed how the information yielded by a test depends on the choice of cutoff and on the patient's pre-test probability of having the disorder. In this article, we demonstrate a method of optimizing a test's information yield that allows us to determine which of several tests gives the most information. Our technique allows us to compare a test's performance with that of a perfect diagnostic test. PMID- 1627985 TI - More on ECT and delirium in Parkinson's disease. PMID- 1627986 TI - Fluoxetine and schizophrenia in a patient with obsessional thinking. PMID- 1627987 TI - The Babinski response and periodic limb movement disorder. PMID- 1627988 TI - Unforeseen beneficial effects of controlled-release levodopa-carbidopa (Sinemet CR) PMID- 1627989 TI - Patterns of lifetime drug use among intravenous drug users. AB - To obtain a clearer description of the natural history of intravenous drug use (IVDU), 92 intravenous drug users (IVDUs), not selected through treatment or contact with the legal system, were identified. Concerning lifetime use, central nervous system (CNS) stimulants were the most common class of drug to be injected (by 72.8% of IVDUs), followed by opiates (by 50.0% of IVDUs). Mean age of onset of IVDU in this sample was 18.5 years, following initiation of alcohol use by an average of 4.6 years and cannabis use by an average of 2.1 years. Any history of IVDU in this sample indicated substantial lifetime use of illicit drugs and early onset of psychoactive substance use. PMID- 1627990 TI - Characteristics of adult children of alcoholics. AB - Ninety-seven adult children of alcoholics (ACOAs), 36 adults with dysfunctional family histories, and 41 adults without identified dysfunctional family histories were compared on self-reports of 20 adult characteristics. Significant differences among the groups were found on 4 of the characteristics, with the ACOA group showing the highest frequency of occurrence on 17 of them. No differences due to gender of the alcoholic parent were found, and there was no group by gender interaction. The results suggested that the clinical characteristics attributed to ACOAs may have some empirical validity but the ACOAs seem fairly similar to adults with other types of dysfunctional family histories. PMID- 1627991 TI - The context of smoking initiation and maintenance: findings from interviews with youths. AB - The characteristics of initial cigarette-smoking situations and subsequent situations in which adolescents received an offer to smoke were examined by means of interviews with 287 youths in grades 7 through 10. Initiation of smoking generally took place in a social context (89%), with small groups (2.7 people) of same-gender, older (2.1 years), peers (and siblings) who were smokers (60%). In one-third of these onset situations, another novice smoked for the first time. Most subjects (81%) reported that they smoked their first cigarette because they accepted an offer. The characteristics of the onset situation did not significantly differ between regular and experimental smokers. The situations for later offers to smoke were similar: small groups of same-gender, slightly older, cigarette-smoking peers (and siblings). Descriptive and comparative data also are presented on procurement, perceived prevalence, parental influence, cravings, quit attempts, beliefs about ease of quitting, and intention to smoke. These data suggest that school-based interventions may not be sufficient to address the broad social context surrounding adolescent tobacco use. Community-wide interventions are advocated. PMID- 1627992 TI - Relationships among smoking status, body composition, energy intake, and physical activity in adult males: a longitudinal analysis. AB - This study evaluates the longitudinal relationships among smoking and adiposity, dietary intake, and physical activity in a group of adult males. Subjects were 101 nonsmokers and 19 regular cigarette smokers. Adiposity, dietary intake, and physical activity were assessed annually for three consecutive years. Results indicated that nonsmokers had larger tricep skinfold measurements than smokers over the 3-year period. However, dietary intake and physical activity did not differ between groups. Due to the absence of differences on these two variables for the smoking and nonsmoking groups, it was concluded that the lower adiposity in smokers was largely metabolically determined, which may make difficult the treatment of postcessation weight gain. PMID- 1627993 TI - Abuse of drugs associated with eating disorders. AB - Concomitant bulimia nervosa and drug abuse are common in women. Drugs used by this group include diuretics, emetics, laxatives, and diet pills, as well as alcohol, cigarettes, and illicit street drugs. This paper applies principles from behavioral pharmacology to the problem of drug use by women with bulimia nervosa. The prevalence of use, primary effects, toxicity, detection, tolerance, withdrawal, and effects on appetite and weight are discussed for drugs used by bulimic women to reduce appetite or weight or to induce purging (e.g., diuretics, emetics, laxatives, and diet aids). Alternatives in the diagnosis and treatment of drug use in women with eating disorders are discussed. PMID- 1627994 TI - The impossible dream?--Routes to reducing alcohol problems in a temperance culture. AB - Two main prescriptions are offered for reducing rates of alcohol problems in English-speaking and Nordic cultures: a "dry" solution of reducing the physical and cultural availability of alcohol, and a "wet" solution of reducing problems of intoxication by better integrating drinking into the culture. Empirical evaluations of change in particular cultures have tended to support the dry, and not the wet, solution. But such studies focus on relatively short-term effects, and there is evidence that long-run effects may be weaker or may even be reversed from shortterm effects. Some particular societies that have been put forward as examples of the long-term success of wet strategies are considered. The most likely success from this perspective is the Netherlands, which is also an exceptional society in terms of the wetness of its drug policies. In the light of these cases, consideration is given to some issues concerning the criteria for evaluating the success of one or the other solution. It is argued that alcohol policy discussions need to recognize that intoxication has a particular social position in our societies, in terms of characteristics of the drinker and of the occasion, in terms of intoxication's cultural significance, and in terms of its entrenchment in social worlds of heavy drinking. Some implications for policy are noted. PMID- 1627995 TI - Women's health: a focus for the 1990s. PMID- 1627996 TI - It's time for selected routine testing of newborns for human immunodeficiency virus. PMID- 1627997 TI - Pregnant women's knowledge of the human immunodeficiency virus: implications for education and counseling. PMID- 1627998 TI - Obstetricians' and gynecologists' beliefs and preferred modes of treatment for women diagnosed with premenstrual symptoms. PMID- 1627999 TI - Women's health: the making of a powerful new public issue. PMID- 1628000 TI - Abortion in nineteenth century America: a conflict between women and their physicians. PMID- 1628001 TI - Sexism and medical terminology. PMID- 1628002 TI - Work and pregnancy. PMID- 1628003 TI - Alternative analysis of the review of work during pregnancy. PMID- 1628004 TI - Prenatal care incentives. PMID- 1628005 TI - Physicians and the basic human rights of women. PMID- 1628006 TI - The road to Rio. PMID- 1628007 TI - A meeting of rich and poor. PMID- 1628008 TI - After Windscale (Sellafield) PMID- 1628009 TI - Alcohol and cardiac arrhythmias. PMID- 1628010 TI - Percutaneous endoscopic gastrostomy. PMID- 1628011 TI - Implementing the patient's charter in outpatient services. PMID- 1628012 TI - Incidence of leukaemia and other cancers in birth and schools cohorts in the Dounreay area. AB - OBJECTIVE: To determine whether a raised incidence of leukaemia in the Dounreay area occurred in children born to local mothers (birth cohort) or in those who moved to the area after birth (schools cohort) and also whether any cases of cancer have occurred in children born near Dounreay who may have moved elsewhere. DESIGN: Follow up study. SETTING: Dounreay area of Caithness, Scotland. SUBJECTS: 4144 children born in the area in the period 1969-88 and 1641 children who attended local schools in the same period but who had been born elsewhere. MAIN OUTCOME MEASURES: Cancer registration records linked to birth and school records with computerised probability matching methods. RESULTS: Five cancer registrations were traced from the birth cohort compared with 5.8 expected on the basis of national rates (observed to expected ratio 0.9, 95% confidence interval 0.3 to 2.0). All five cases were of leukaemia (2.3, 0.7 to 5.4). In the schools cohort three cases were found (2.1, 0.4 to 6.2), all of which were of leukaemia (6.7, 1.4 to 19.5). All eight children were resident in the Dounreay area at the time of diagnosis; thus no cases were found in children who were born in or had attended school in the study area but who subsequently moved away. CONCLUSION: The raised incidence of leukaemia in both the birth and schools cohorts suggests that place of birth is not a more important factor than place of residence in the series of cases of leukaemia observed near Dounreay area. PMID- 1628013 TI - Randomised comparison of percutaneous endoscopic gastrostomy and nasogastric tube feeding in patients with persisting neurological dysphagia. AB - OBJECTIVE: To compare percutaneous endoscopic gastrostomy and nasogastric tube feeding in patients with persisting neurological dysphagia. DESIGN: Randomised 28 day study of inpatients requiring long term enteral nutrition. SETTING: Three Glasgow teaching hospitals. SUBJECTS: 40 patients with dysphagia for at least four weeks secondary to neurological disorders: 20 patients (10 women) were randomised to nasogastric feeding and 20 (eight women) to endoscopic gastrostomy. MAIN OUTCOME MEASURES: Treatment failure (blocked or displaced tubes on three or more occasions or refusal to continue treatment); duration of feeding; intake of liquid diets; complications; nutritional status at end of trial. RESULTS: One patient in each group died before starting feeding. Treatment failure occurred in 18 of the 19 nasogastric patients and in none of the gastrostomy group. The mean (SE) duration of feeding for the nasogastric group was 5.2 (1.5) days. No complications occurred in the nasogastric group but three (16%) of the gastrostomy group developed minor problems (aspiration pneumonia (two patients) wound infection (one)). Gastrostomy patients received a significantly greater proportion of their prescribed feed (93% (2%)) compared with the nasogastric group, (55% (4%); p less than 0.001) and also gained significantly more weight after seven days of feeding (1.4 (0.5) kg v 0.6 (0.1) kg; p less than 0.05). Analyses at days 14, 21, and 28 were not possible due to the small numbers remaining in the nasogastric group. CONCLUSION: Percutaneous endoscopic gastrostomy tube feeding is a safe and effective method of providing long term enteral nutrition to patients with neurological dysphagia and offers important advantages over nasogastric tube feeding. PMID- 1628014 TI - Trends in deliberate self poisoning and self injury in Oxford, 1976-90. AB - OBJECTIVE: To review trends in deliberate self poisoning and self injury (attempted suicide) over 15 years (1976-90) on the basis of general hospital referrals. DESIGN: Prospective data collection by computerised monitoring system. SETTING: Teaching general hospital. SUBJECTS: All patients aged 15 and over (n = 9605) referred to the hospital after episodes (n = 13,340) of deliberate self poisoning or self injury. MAIN OUTCOME MEASURES: Rates based on population of Oxford city; changes in substances used for self poisoning; history and repetition of attempts; and rates of admission to the hospital and of referral to the psychiatric service. RESULTS: Attempted suicide rates for women declined during the late 1970s and early 1980s but increased again during the late 1980s. Those for men remained relatively steady throughout the period. Highest mean annual rates occurred in women aged 15-19 (711/100,000) and in 20-34 year old men (334/100,000). The proportion of overdoses with paracetamol increased from 14.3% (125/873) in 1976 to 42% (365/869) in 1990 (chi 2 for trend = 481, p less than 0.01). Throughout the period the proportions of referred patients admitted to hospital and of those attempting suicide for the first time (over two thirds) did not decrease. Annual rates of repetition of attempts by women declined from 15.1% (257/1700) in 1976-8 to 11.9% (161/1356) in 1987-9 (chi 2 for trend = 7.8, p less than 0.01). Lower repetition rates occurred in women admitted to hospital and referred to the psychiatric service (431/4585, 9.4%) than in those not referred (42/235, 17.9%; chi 2 = 17.2, p less than 0.0001). CONCLUSIONS: Rates of attempted suicide declined in the 1970s and early 1980s, in women, but there are probably at least 100,000 hospital referrals a year in England and Wales because of this problem. Prevention of paracetamol self poisoning requires urgent attention, and psychosocial assessment should be conducted with as many of those who attempt suicide as possible. PMID- 1628015 TI - Gonad protection in young orthopaedic patients. AB - OBJECTIVE: To determine whether gonad shields are correctly positioned on the pelvic radiographs of children with slipped capital femoral epiphysis. DESIGN: Retrospective study of radiographs taken of children treated by in situ pinning of slipped capital femoral epiphysis between 1 January 1983 and 31 December 1988. SETTING: Three teaching hospitals in north west England. PATIENTS: 32 patients with complete set of radiographs. RESULTS: An average of 10.8 anteroposterior pelvic radiographs plus 8.9 lateral hip radiographs had been performed per patient. Gonad shields had been completely omitted in 137 (40%) anteroposterior pelvic radiographs performed on the 32 patients at the time of completion of the study. In 100 (29%) the gonad shields were adequately protecting the gonads, but in 109 (31%) the gonad shields were not protecting the gonads due to incorrect positioning of the shield. The incorrect positioning of the gonad shields was more commonly found in girls than boys (64 vs 45; p less than 0.012), presumably because of the difficulty in determining gonadal position in relation to surface landmarks. Absence of gonad shields was also more commonly seen in girls (82 v 55; p less than 0.005), but this is not easily explained. CONCLUSIONS: Gonad shields are not protecting the gonads in a large percentage of anteroposterior pelvic radiographs (71%) because they have been omitted or inadequately placed. This avoidable excess radiation exposure to the gonads, combined with the inability to shield the gonads in lateral hip radiographs and the large number of radiographs performed, results in the gonads receiving a higher dose of radiation than may otherwise be the case, and may increase the potential for disease in the future offspring of these patients. PMID- 1628016 TI - Murmurs in pregnancy: an audit of echocardiography. PMID- 1628017 TI - Acute adrenal insufficiency associated with high dose inhaled steroids. PMID- 1628018 TI - Cardiac arrest associated with flumazenil. PMID- 1628019 TI - National general practice study of epilepsy: the social and psychological effects of a recent diagnosis of epilepsy. AB - OBJECTIVES: To determine the nature and extent of psychosocial problems in epilepsy and their associations. DESIGN: A postal survey was used drawing data from prospective consecutive cases. Data on demographic, medical, and social backgrounds were collected. A specially designed, validated attitude questionnaire examined 14 areas of psychosocial adjustment to epilepsy. SETTING: 124 primary care general practices. SUBJECTS: Adults (aged over 17) with a recent diagnosis of epilepsy (within previous 36 months). They were registered with the national general practice study of epilepsy and had a confirmed diagnosis according to the usual criteria. 216 subjects were approached for the survey by their general practitioners; 192 returned questionnaires. RESULTS: Problems in at least one area were experienced by 175 (91%) of the 192 subjects. Problems were generally mild, which contrasts strongly with findings in chronic cases. The areas of greatest concern were fear of seizures (80% of cases; 72% moderate or severe) and fear of stigma in employment (69% of cases; 40% moderate or severe). A highly significant relation was found between psychosocial effects and the frequency and recency of seizures. CONCLUSIONS: In the early stages of epilepsy psychosocial effects are closely related to the severity of the medical condition, suggesting that the argument for the stigmatising effect of the diagnosis by itself is less important than previously thought. The findings also suggest that problems may evolve as the condition becomes chronic. PMID- 1628020 TI - Learning from the past. PMID- 1628021 TI - Military expenditure and foreign aid: should they be linked? PMID- 1628022 TI - The great exterminator of children. PMID- 1628023 TI - Testicular cancer and related neoplasms. PMID- 1628024 TI - Too many advisers, not enough aid. PMID- 1628025 TI - Helping Russia. PMID- 1628026 TI - ABC of colorectal diseases. Diverticular disease. PMID- 1628027 TI - Rationing in developing countries. PMID- 1628028 TI - Measles, mumps, and rubella vaccination. PMID- 1628029 TI - Harm minimisation for drug misusers. PMID- 1628030 TI - Storing vaccines at the correct temperature. PMID- 1628031 TI - Managing drug misuse in general practice. PMID- 1628032 TI - For and against Eusol. PMID- 1628033 TI - Adrenaline in allergic emergencies. PMID- 1628034 TI - Steroid ulcers. PMID- 1628035 TI - Advanced trauma life support. PMID- 1628036 TI - Octreotide and urinary glycosaminoglycan in Graves' disease. PMID- 1628037 TI - Reversing vasectomy. PMID- 1628038 TI - Advanced trauma life support care. PMID- 1628039 TI - Behcet's disease. PMID- 1628040 TI - Diagnosing pulmonary embolism. PMID- 1628041 TI - Free For All: "Cancer positive". PMID- 1628042 TI - Improving postgraduate training in ophthalmology. PMID- 1628043 TI - Ethics and multicentre research projects. PMID- 1628044 TI - Ethics of embryo manipulation. PMID- 1628045 TI - Fellowships for doctors from Czechoslovakia. PMID- 1628046 TI - Sexual contact between doctors and patients. PMID- 1628047 TI - Living bone grafts. PMID- 1628048 TI - Investigating lower bowel symptoms in general practice. PMID- 1628049 TI - Cardiac imaging with radionuclides. PMID- 1628050 TI - Sexual contact in the doctor-patient relationship in The Netherlands. AB - OBJECTIVE: To obtain data on sexual contact between doctors and their patients. DESIGN: Anonymous questionnaire with 17 items sent to all working gynaecologists (n = 595) and all ear, nose, and throat specialists (n = 380) in the Netherlands. RESULTS: Response rate was 74%; a total 64 doctors gave a reason for not completing the questionnaire. 201 (59%) male gynaecologists and 128 (56%) male ear nose, and throat specialists indicated that sexual feelings are acceptable in the doctor-patient relationship; 286 (85%) and 186 (81%), respectively, had felt sexually attracted to a patient at some time, as had 14 (27%) female gynaecologists. More than half (59%) of the doctors who indicated that sexual feelings are unacceptable in the doctor-patient relationship had experienced these feelings, and 91% of this group had a negative attitude towards these feelings. 4% of respondents in each group had had actual sexual contact with patients. Most gynaecologists were in favour of having more attention paid to sexual problems during training; having their professional society take an official viewpoint; subsequent public support of this viewpoint; and taking on an impartial counsellor for the patients as well as the doctors. CONCLUSION: Sexuality exists in the doctor-patient relationship. Gynaecologists have a higher risk of having sexual contact with their patients than do ear, nose, and throat specialists but compensate for this greater risk by a higher state of recognition and acknowledgement. PMID- 1628051 TI - Symptoms after accelerated immunisation. AB - OBJECTIVE: To document the incidence of symptoms after accelerated immunisation with diphtheria-tetanus-pertussis vaccine. DESIGN: Controlled study of children immunised with adsorbed diphtheria-tetanus-pertussis vaccine at accelerated and standard schedules. SETTING: Colchester and north Hertfordshire. SUBJECTS: 107 children scheduled to receive immunisation at 2, 3, and 4 months of age and 115 children scheduled to receive immunisation at 3, 4 1/2 to 5, and 8 1/2 to 11 months of age. MAIN OUTCOME MEASURES: Parentally recorded symptoms, axillary temperatures, and size of local redness and swelling at the injection site during the seven days after immunisation. RESULTS: In general symptoms occurred less frequently with the accelerated schedule. Proportions of parents reporting axillary temperatures greater than 37.2 degrees C or local redness or swelling greater than 2.5 cm after the third dose of vaccine were significantly reduced in the accelerated schedule group. CONCLUSION: Immunisation at 2, 3, and 4 months of age is likely to cause fewer reactions than immunisation at 3, 4 1/2 to 5, and 8 1/2 to 11 months of age. PMID- 1628053 TI - Endoscopy facilities in general practice. PMID- 1628052 TI - Detection of IgA and IgM antibodies to HIV-1 in neonates by radioimmune western blotting. AB - OBJECTIVE: To detect infection with HIV-1 by IgA and IgM response at birth in children born to HIV-1 seropositive mothers. DESIGN: Western blotting and radioimmune western blotting on stored sera from infected and uninfected babies born to HIV-1 seropositive mothers. Sera were pretreated to remove IgG. SETTING: Parma and Bologna, Italy. SUBJECTS: 12 infected and five uninfected babies born to HIV-1 seropositive mothers and three babies born to seronegative mothers. MAIN OUTCOME MEASURES: Effectiveness of western blotting and radioimmune western blotting in detecting antibodies to HIV-1 gene products. RESULTS: With conventional western blotting we found IgA class antibodies to HIV-1 proteins in serum from three out of 12 infected children; in two of these three the serum was collected at age 3 months (positive controls). Radioimmune western blotting detected both IgA and IgM antibodies in serum from all infected children tested, whereas all serum from uninfected children born to seropositive and seronegative mothers showed no such antibodies. CONCLUSION: Although the technique should be tested on more patients, radioimmune western blotting seems to be a valuable tool for serological diagnosis of congenital HIV-1 infection at birth in neonates born to seropositive mothers. PMID- 1628054 TI - Oesophageal cancer and distilleries in Scotland. PMID- 1628055 TI - Unnecessary hospitalisation in a psychiatric rehabilitation unit. PMID- 1628056 TI - Job stress, satisfaction, and mental health among general practitioners before and after introduction of new contract. AB - OBJECTIVE: To compare measures of job stress, job satisfaction, and mental health among general practitioners before and after the introduction of the new contract in April 1990. DESIGN: Cross sectional postal questionnaire survey in July 1990. Comparison of results with those obtained in previous survey in November 1987. SETTING: General practice in United Kingdom. SUBJECTS: 1500 general practitioners randomly selected from general medical services lists, 917 of whom (61%) returned questionnaires usable for statistical analysis. MAIN OUTCOME MEASURES: Aspects of job causing stress, job satisfaction (Warr, Cook, and Wall scale), and mental health (Crown-Crisp experiential index). RESULTS: Compared with 1987, in 1990 doctors experienced more stress from night calls (mean score 3.83 in 1990 v 3.45 in 1987), emergencies during surgery hours (3.72 v 3.48), and interruption of family life by telephone (3.58 v 2.73; p less than 0.001 for all three variables). Scores for somatic anxiety and depression were higher in both men and women in 1990 (men: somatic anxiety 3.12 v 2.36; depression 3.80 v 2.94; women: somatic anxiety 3.56 v 2.65; depression 4.02 v 3.37; p less than 0.001). Job satisfaction had also decreased in 1990 (5.23 v 4.26; p less than 0.001). CONCLUSIONS: Doctors experienced more stress, less job satisfaction, and poorer mental health in 1990 than in 1987. These changes may have resulted from the introduction of the new contract. PMID- 1628057 TI - Imposed change in general practice. PMID- 1628058 TI - The law, medical students, and assault. PMID- 1628060 TI - Post-totalitarian medicine. PMID- 1628059 TI - Radiotherapy update. PMID- 1628061 TI - ABC of colorectal diseases. Colorectal neoplasia--II: Large bowel cancer. PMID- 1628062 TI - Managing sudden bereavement. PMID- 1628063 TI - Postviral fatigue syndrome. PMID- 1628064 TI - Postviral fatigue syndrome. PMID- 1628065 TI - Postviral fatigue syndrome. PMID- 1628066 TI - Postviral fatigue syndrome. PMID- 1628067 TI - Managing tuberculosis and HIV infection. PMID- 1628068 TI - Ernest Saunders: diagnostic dilemma. PMID- 1628069 TI - Cholera in Brazil. PMID- 1628070 TI - Provision of home births. PMID- 1628071 TI - Psychological treatments for patients with cancer. PMID- 1628072 TI - Treatment of elderly patients with breast cancer. PMID- 1628073 TI - Deaths from hemolytic disease of the newborn. PMID- 1628074 TI - Delayed diagnosis in NIDDM. PMID- 1628075 TI - Elderly people placed in wrong homes. PMID- 1628076 TI - Lung cancer and radon. PMID- 1628077 TI - Underfunding of inner city general practice. PMID- 1628078 TI - Developing a hospital information strategy. PMID- 1628079 TI - NHS distribution of funds unfair. PMID- 1628081 TI - Compulsory admission of dangerous psychopaths. PMID- 1628080 TI - Obstetrical history of Queen Anne. PMID- 1628082 TI - The future of primary health care. PMID- 1628083 TI - Listeriosis. PMID- 1628084 TI - Pernicious anaemia. PMID- 1628085 TI - "Macho" management in the NHS. PMID- 1628086 TI - Electrocardiographic abnormalities and associated factors in Chinese living in Beijing and in Mauritius. The Mauritius Non-Communicable Disease Study Group. AB - OBJECTIVE: To compare the prevalence of electrocardiographic abnormalities and to evaluate the association between these abnormalities and the levels of coronary heart disease among Chinese living in different environments. DESIGN: Cross sectional surveys. SETTING: Beijing, China, and the island of Mauritius. SUBJECTS: Random samples of people aged 35-64 years in Beijing (621 men, 642 women) in 1984 and in Mauritius among Chinese (137 men, 130 women) and non Chinese (1265 men, 1432 women) in 1987. MAIN OUTCOME MEASURES: Prevalence of electrocardiographic abnormalities suggesting coronary heart disease and of associated risk factors. RESULTS: Prevalence of electrocardiographic abnormalities suggesting coronary heart disease was significantly lower in Beijing (4.0%) than in Mauritian Chinese (24.3%) and Mauritian non-Chinese (24.5%). Mean serum concentrations of total and non-high density lipoprotein cholesterol were lower in Beijing Chinese than in Mauritian Chinese, but smoking and hypertension were slightly more prevalent. Overall, men with electrocardiographic abnormalities had higher risk factor levels than those with a normal electrocardiogram regardless of ethnic origin. CONCLUSIONS: The prevalence of coronary heart disease and associated risk factors was different among Chinese living in two different environments: in Beijing in the People's Republic of China and in Mauritius. Chinese, who traditionally have a very low frequency of coronary heart disease, are by no means protected against coronary heart disease and other non-communicable diseases. Therefore, primary prevention of coronary heart disease is a major challenge for preventive medicine in China, as well as in many other developing countries. PMID- 1628087 TI - Growth hormone and tumour recurrence. AB - OBJECTIVE: To determine whether using growth hormone to treat radiation induced growth hormone deficiency causes tumour recurrence. DESIGN: Comparison of tumour recurrence rates in children treated with growth hormone for radiation induced deficiency and an untreated population. Computed tomograms from children with brain tumours were reviewed when starting growth hormone and subsequently. SETTING: North West region. PATIENTS: 207 children treated for brain tumour, 47 of whom received growth hormone and 161 children with acute lymphoblastic leukaemia 15 of whom received growth hormone. MAIN OUTCOME MEASURES: Tumour recurrence and changes in appearances on computed tomography. RESULTS: Among children with brain tumour, five (11%) who received growth hormone had recurrences compared with 42 (26%) who did not receive growth hormone. Also adjusting for other variables that might affect tumour recurrence the estimated relative risk of recurrence was 0.82 (95% confidence interval 0.28 to 2.37). The only child with acute lymphoblastic leukaemia who relapsed while taking growth hormone had relapsed previously before starting treatment. Two of the five children with brain tumours who relapsed had abnormal appearances on computed tomography when growth hormone was started. 14 other children who remained relapse free and had follow up computed tomography showed no deterioration in radiological appearance during treatment. CONCLUSIONS: In this population growth hormone did not increase the risk of tumour recurrence but continued surveillance is essential. Abnormal results on computed tomography are not a contraindication to treatment with growth hormone. PMID- 1628089 TI - Effects of long term octreotide on gall stone formation and gall bladder function. PMID- 1628088 TI - Effect of serotesting with counselling on condom use and seroconversion among HIV discordant couples in Africa. AB - OBJECTIVE: To determine whether HIV testing and counselling increased condom use and decreased heterosexual transmission of HIV in discordant couples. DESIGN: Prospective study. SETTING: Kigali, the capital of Rwanda. SUBJECTS: Cohabiting couples with discordant HIV serology results. MAIN OUTCOME MEASURES: Condom use in the couple and HIV seroconversion in the negative partners. RESULTS: 60 HIV discordant couples were identified, of whom 53 were followed for an average of 2.2 years. The proportion of discordant couples using condoms increased from 4% to 57% after one year of follow up. During follow up two of the 23 HIV negative men and six of the 30 HIV negative women seroconverted (seroconversion rates of 4 and 9 per 100 person years). The rate among women was less than half that estimated for similar women in discordant couples whose partners had not been serotested. Condom use was less common among those who seroconverted (100% v 5%, p = 0.01 in men; 67% v 25%, p = 0.14 in women). CONCLUSIONS: Roughly one in seven cohabiting couples in Kigali have discordant HIV serological results. Confidential HIV serotesting with counselling caused a large increase in condom use and was associated with a lower rate of new HIV infections. HIV testing is a promising intervention for preventing the spread of HIV in African cities. PMID- 1628090 TI - Oral and dental disease in terminally ill cancer patients. PMID- 1628092 TI - Managing change in primary care. Meetings and chairmanship. PMID- 1628091 TI - Roles, risks, and responsibilities in maternity care: trainees' beliefs and the effects of practice obstetric training. AB - OBJECTIVES: To document the content of practice obstetric vocational training, the beliefs of general practitioner trainees about the roles of midwives and general practitioners in maternity care, and the risks of providing such care; and to ascertain if undergoing such training affects their beliefs. DESIGN: Confidential postal questionnaire survey. SUBJECTS: Random one in four sample of all general practitioner trainees in the United Kingdom on vocational training schemes or in training practices in autumn 1990. MAIN OUTCOME MEASURES: Beliefs scored on seven point Likert scales and characteristics of trainer and training practice. RESULTS: Of 1019 trainees sent questionnaires, 765 (75.1% response rate) replied; 638 (83.3%) had done some part of their practice year. Of their trainers, 224 (35.1%) provided full obstetric care. 749 (99%) and 364 (48%) trainees believed that midwives and general practitioners respectively have an important role in normal labour; 681 (91.7%) trainees believed that general practice intrapartum care is a high risk "specialty." Those trainees whose trainers provide full obstetric care were significantly more likely to believe that both midwives and general practitioners have an important role in abnormal labour and to see the provision of intrapartum care as an incentive to join a practice. CONCLUSION: In this series most general practitioner trainees believed that both midwives and general practitioners have important roles in maternity care. Exposure of trainees to the provision of full obstetric care while in their training practice resulted in a more positive attitude towards the provision of such care by general practitioners. PMID- 1628093 TI - How to run an induction meeting for house officers. PMID- 1628094 TI - ABC of colorectal diseases. Colorectal neoplasia--III: Treatment and prevention. PMID- 1628095 TI - Intra-arterial temazepam. PMID- 1628096 TI - Intra-arterial temazepam. PMID- 1628097 TI - Life events and breast cancer prognosis. PMID- 1628098 TI - Life events and breast cancer prognosis. PMID- 1628099 TI - Psychological influences on cancer and ischaemic heart disease. PMID- 1628100 TI - Altitude induced illness. PMID- 1628101 TI - Asthma deaths in New Zealand. PMID- 1628102 TI - Row over Maori cot death rate. PMID- 1628103 TI - Adrenaline in allergic emergencies. PMID- 1628104 TI - Recording HIV status on police computers. PMID- 1628105 TI - Eusol: the continuing controversy. PMID- 1628106 TI - Eusol: the continuing controversy. PMID- 1628107 TI - Early and late replicating DNA involved in the G1 to S transition in Allium cepa L meristematic cells. AB - The involvement of portions of the genome replicated at different times of the S period in the regulation of the G1 to S transition was analyzed in Allium cepa L meristem cells. For this, DNA bromosubstitution confined to discrete portions of a previous S period followed by anoxic UVA irradiation (300-400 nm light) was performed in synchronous cells. Sequences replicated in late S appeared to be involved in the positive regulation of the initiation of replication. Hence, cells were prevented from initiating replication if irradiated at mid G1 only when the DNA sequences replicated in the last third of the previous S period were bromosubstituted. Cycloheximide-induced inhibition of protein synthesis at late G1 also prevented the G1 to S transition. Sequences replicated in mid S appeared unrelated to any control of the initiation of replication. On the other hand, sequences replicated in the first third of the S period seemed to be involved in the negative regulation of the initiation of replication, since irradiation after previous bromosubstitution of early replicating DNA sequences advanced G1 cells into the next S phase and increased the proliferative fraction of the population. Finally, the simultaneous inactivation of DNA sequences involved in both positive and negative regulation of replication allowed the cells to enter into S. PMID- 1628108 TI - Cytochalasin induces spindle fusion in the syncytial blastoderm of the early Drosophila embryo. AB - Microfilament integrity is needed to maintain the regular arrangement of the spindle microtubules and to guarantee the normal progression of the last syncytial mitoses in Drosophila embryo. To investigate when and how microfilaments participate in this process, we incubated permeabilized embryos with the inhibitor of actin polymerization, cytochalasin B, at different times during the nuclear cycle. Our results suggest that the correct microfilament distribution is only required for the appropriate segregation of nuclei during the 11th, 12th and 13th syncytial mitoses rather than during the 10th mitosis when the spindles are too far apart to interact. When cytochalasin B treatment was performed during the last syncytial mitoses many spindles fuse among them and the regular mitotic progression is perturbed. PMID- 1628109 TI - Serum-free culture of stromal and functionally polarized epithelial cells of guinea-pig endometrium: a potential model for the study of epithelial-stromal paracrine interactions. AB - Stromal and glandular epithelial (GE) cells were isolated from guinea-pig endometrium and growth to near confluency (6-8 days) in primary culture on plastic surfaces in a serum-supplemented medium (SSM). The stromal cells were subcultured on plastic dishes and maintained for 72 h in SSM. Then SSM was replaced by a chemically defined medium (CDM) and the stromal cells grown to confluency (5-7 days). The GE cells were subcultured in CDM, on a basement membrane matrix (Matrigel) applied to permeable Millicell-PC filters, and grown to confluency (5 days). Homogeneity of the subcultured endometrial cell populations was ascertained immunocytochemically. The filter-cultured GE monolayers were polarized morphologically, and displayed epithelial-specific specialized structures. These monolayers had functional tight junctions as verified by a measurable transepithelial resistance. The subcultured cell populations were distinguished by an analysis of their cellular and secretory proteins after labelling with [35S]-methionine and analysis by polyacrylamide gel electrophoresis. The filter-cultured GE monolayers allowed identification of the proteins released vectorially in the apical or the basal secretory compartment, thus demonstrating the functional polarization of GE cells in this bicameral culture system. Within the defined conditions of this culture system, the paracrine factors released by the two endometrial cell populations as well as the interplay of stromal-epithelial interactions and ovarian hormones could be investigated. PMID- 1628110 TI - In vitro effect of fungal cyclodepsipeptides on leukemic cells: study of destruxins A, B and E. AB - The activities of three mycotoxins isolated from the hyphomycete Metarhizium anisopliae: destruxin A, B, and E (DA, DB and DE) are described and compared in vitro on leukemic cells. Their antitumor effect was investigated by flow cytometry on growth, cell viability and cell cycle perturbation 48 h after destruxin exposure. Against P388 leukemic cells, DE displayed greater antiproliferative activity than DA and DB. The minimum concentration required to inhibit 50% of cell proliferation is 0.33 microgram/ml for DE, 11.7 micrograms/ml for DA and 9.4 micrograms/ml for DB. Cell cycle modifications were only observed with DE at 50 and 10 micrograms/ml and consisted in an accumulation of the cells in G0/1 phase. DA and DB did not modify the number of cells in G0/1 of the cell cycle. Nevertheless a decrease in the number of cells in G2+M phase was induced by the three destruxins. PMID- 1628111 TI - Adriamycin resistance is characterized by ultrastructural changes in human leukaemic K562 cells in vitro. AB - Ultrastructural changes associated with adriamycin (ADM) resistance have been investigated in the human K562 leukaemic cell line: sensitive K562 cells, a resistant subline cultured in the continuous presence of ADM and resistant cells without ADM Transmission electron microscopy (TEM) study revealed that K562 resistant cells displayed ultrastructural modifications of the cell surface, chromatin and nucleolus conformation. Alterations were not directly related to the presence of adriamycin as deprivated cells exhibited modificated characters through a slow progressive recovery phenomenon. PMID- 1628112 TI - Pattern of arborization of the motor nerve terminals in the fast and slow mammalian muscles. AB - A silver impregnation method and a morphometric approach were used to define differences existing in the motor nerve terminal branching pattern between a fast twitch muscle (extensor digitorum longus) and a slow-twitch one (soleus) of the normal adult rat. Because no single measure can describe precisely all geometrical properties (ie both topology and metrics) of the nerve terminals, we evaluated morphologic parameters defining length and angular characteristics in the different terminal segments classified according to their centrifugal order. The main results indicate that the distal free-end segments in the extensor digitorum longus muscle are shorter and less divergent than in the soleus nerve terminals. The endings in the two muscles have different fractal dimensions. Findings are discussed in the context of the hypothetical mechanisms governing motor nerve terminal size and complexity. PMID- 1628113 TI - Liver peroxisomes in newborns from clofibrate-treated rats. I. A morphometric study of the recovery period. AB - Morphological and morphometric parameters (volume density (Vv), numerical density (NA) and mean diameter (D)) of newborn liver peroxisomes were measured throughout the first week of life in rats born to mothers treated with clofibrate (ethyl 2 p chlorophenoxy isobutyrate) during the last five days of pregnancy. In control studies the same analyses were carried out in newborns from untreated rats. At birth (day 0), treated animals exhibited a proliferated, pleiomorphic peroxisomal population (higher Vv, NA and D, and a spread distribution of profile diameter with respect to the controls). In the subsequent two days, many peroxisomes disappeared (decrease of Vv and NA to values even lower than controls), with a persisting high pleiomorphism (no change of D and diameter distribution) in residual ones. Starting from day 3, and up to day 6, larger peroxisomes were no longer detectable in test animals, and a significant, not pleiomorphic proliferation took place (D and diameter distributions strictly comparable to the controls and progressively increasing Vv and NA). The correlation analysis validated these morphological results, from which it can be surmised that the postnatal peroxisome recovery period consists of a destructive phase followed by a proliferative one. The possible mechanism(s) of disposal of the excess of drug induced peroxisomes are discussed. PMID- 1628114 TI - Liver peroxisomes in newborns from clofibrate-treated rats. II. A biochemical study of the recovery period. AB - The fatty-acyl-CoA beta-oxidation (FAO) and catalase activities, as well as membrane fluidity of liver peroxisomes of newborns from normal and clofibrate treated rats were studied during the recovery period, ie, throughout the first week of postnatal life. In the test animals the enzyme activities, which are significantly higher than controls at birth return to normal levels showing a somewhat different time course with FAO rapidly decreasing to control values within three days but with catalase still higher than controls at day 6. The half life and degradation rate (Kd) of FAO are identical to those calculated by us for the whole organelles and to those reported by others for total catalase in normal or clofibrate-treated adult animals in the presence of catalase inhibitors. Soluble catalase shows turnover values which are similar though not identical to those of FAO, while total catalase has a very long half-life and a low Kd. Peroxisomal membrane fluidity, as determined by fluorescence anisotropy of 1 anilinonaphthalene-8-sulfonate (ANS) bound to purified peroxisomal fractions is higher in tests than in controls, recovering normal values within 6 days. Our results demonstrate that liver peroxisomes of rats prenatally exposed to clofibrate return to control conditions within about 1 week. The turnover parameters of enzymes and the membrane fluidity values are discussed in terms of disposal mechanism(s) for the excess of induced peroxisomes. PMID- 1628115 TI - Clinical and genetic heterogeneity in X-linked deafness. AB - The use of molecular techniques in respect of the rare X-linked non-syndromic form of genetic deafness demonstrates that this is a genetically heterogeneous disorder, with evidence for at least two separate gene loci on the X chromosome. Audiological heterogeneity in this condition is emphasized by the observation of both mixed deafness and sensorineural deafness in pedigrees showing evidence for linkage to Xq13-q21. The importance and shortcomings of the audiogram in assessing females who are known gene carriers is discussed. PMID- 1628116 TI - Linking spontaneous otoacoustic emissions and tinnitus. PMID- 1628117 TI - Testing otolith function. AB - Otolithic signals contribute to; (1) perception of orientation and linear motion, (2) generate compensatory eye movements in response to linear acceleration of the head and (3) participate in the co-ordination of movement and balance. Tests of these functions shown to be useful in identifying clinical disorders have been reviewed: (1) Evaluation of orientation to gravity, as estimated by adjustment of the visual vertical, indicates deranged otolith function at a peripheral or central level and the sensitivity of this test can be enhanced by performing estimates during centrifugation on a motorised turntable. Estimation of thresholds of self motion on a parallel swing identifies global reduction or unilateral loss of peripheral function, with central disorders awaiting study. (2) Otolith ocular reflexes to linear head translation can be used to demonstrate overall integrity of peripheral function and reveal central abnormalities. Counter-rolling responses to head roll-tilt and measurements of cyclodeviation of the eyes demonstrate functional asymmetries, with some lateralising value, particularly in central lesions. Global function and asymmetries may also be evaluated by 'head eccentric' rotational testing, which adds a tangential linear acceleration to the angular stimulus. The linear acceleration enhances the canal response by adding an otolith component. (3) Latency and amplitude of surface electro-myography (EMG) responses in the limbs to sudden falls, which can be recorded with the subject suspended on a hinged bed, indicate gross peripheral abnormality of function and can lateralize disorders of CNS motor pathways. It is concluded that some tests of otolith function can be of use in indicating global loss of peripheral otolith function, others are capable of lateralizing a marked loss of function and all have the potential to give information about central disorders. They all have to be interpreted within the clinical context and, unfortunately, none have yet been shown to be sensitive to partial, particularly unilateral, dysfunction. PMID- 1628118 TI - Plight of unreturned tinnitus questionnaires. PMID- 1628119 TI - Test-retest variability using the Liverpool screening audiometer in a field environment. AB - The Liverpool Field Audiometer (LFA) has been developed as a simple, hand-held device for screening audiometry in developing countries. The variability in the outcome of screening using the LFA was studied with 275 primary schoolchildren in five Brisbane schools. A 30 dB HL screening level was used. The device was found to give low test-retest outcome variability at the test frequencies 1000 Hz, 2000 Hz and 4000 Hz. However, variability was high at 500 Hz and caution should be exercised when data at this frequency are obtained. Possible reasons for this low frequency variability are suggested. PMID- 1628120 TI - The epidemiology of childhood hearing impairment: factor relevant to planning of services. AB - In the Nottingham District Health Authority we found that one in 943 babies born between 1983-1986 have a sensorineural or mixed hearing impairment (at 50 dB HL or greater in the better ear averaged over the frequencies 0.5, 1, 2, 4 kHz) that is either congenital or progressive in nature. If this figure is broken down between non-neonatal intensive care unit babies and neonatal intensive care unit (NICU) graduates, we find that one in 174 NICU graduates have a hearing impairment compared with one in 1278 non-NICU babies. Excluding from the non-NICU baby population those with a known family history of hearing impairment, and those with a known relevant syndrome at birth, there is a 10.2 to 1 odds ratio for babies in NICU to have such hearing impairments compared to this restricted 'normal' baby population. In addition NICU babies with a hearing impairment were considerably more likely to have another disability (odds ratio 8.7 to 1). Acquired sensorineural or mixed impairments comprised about 9% of the children with impairments by 3 years of age. Twenty per cent of the patients seen at the Children's Hearing Assessment Centre (CHAC) with better-ear impairment of 95 dB HL or greater had acquired hearing impairments. The mean age of referral for congenital hearing impairments was found to be a function of severity and NICU status. For children with better-ear hearing impairments of 80 dB HL or greater, the mean and median ages of referral were both 8 months (s.d. 4 months). PMID- 1628121 TI - The effects of hearing loss and age of intervention on some language metrics in young hearing-impaired children. AB - This study examined the oral language production abilities of a group of young children with bilateral sensorineural hearing impairments (greater than 25 dB HL). The effects of age of intervention-as indexed by age of detection, referral, first appointment and hearing-aid fitting-and of the severity of their hearing impairments on spoken language and communication were the foci of the study. Children were aged between 27 and 80 months with hearing threshold levels ranging from 32 to 98 dB in the better ear. All were audio- and video-taped in their own homes, in an unstructured play setting with the mother. Measures of expressive language ability were extracted including mean length of utterance, vocabulary size, words per min., total utterance attempts per min., proportion of non-verbal utterances and the proportion of questions asked by the child. No significant correlations were found between the children's hearing impairments and their scores on the language measures once age at interview had been statistically controlled. However, significant correlations were found between the language measures and the ages at which the children received intervention for their hearing impairments, in particular for vocabulary and those language measures denoting the rate and quality of the child's interaction during the episode recorded. This finding is consistent with some of the arguments to be found in the small body of data addressing the question of early intervention. PMID- 1628122 TI - Reconstitution of B cell immunity following bone marrow transplantation. AB - Bone marrow transplant recipients are known to be immunodeficient in cellular and humoral immune responses for months to years. Mechanisms underlying the post transplant immunodeficiency are mostly unknown and therefore it has been difficult to design therapeutic strategies to address this problem. Here, we review studies of post-transplant B cell (humoral) immunity including B cell blood counts, phenotype, function and origin, and the morphology of lymphoid organs. We postulate that the aetiology of post-transplant humoral immunodeficiency is multifactorial, involving: B cell immaturity due to recapitulation of their ontogenesis, and, in some patients, insufficient T cell help and/or exaggerated CD8+ T cell/NK cell suppression. Implications for clinical practice are outlined, e.g. hypersensitivity reactions and autoimmune diseases as part of the differential diagnosis of post-transplant disorders, questionable diagnostic benefit of serologic studies, and usefulness of prophylactic intravenous immunoglobulin. PMID- 1628123 TI - A scheme for daily monitoring of oral mucositis in allogeneic BMT recipients. AB - A system was developed for scoring oral mucositis in order to investigate its connection with fever and bacteraemia due to 'viridans' streptococci. A series of 42 allogeneic bone marrow transplant recipients given demethoxydaunorubicin and total body irradiation for conditioning therapy were monitored daily for the presence of lesions, erythema, oral oedema, pain and dysphagia, each of which was graded numerically at four levels. These values were added together to yield a daily mucositis score (DMS) with a scale of 0-15. Mucositis developed shortly after transplant and progressed within a few days to grade III (WHO grade 3-4) in the majority of patients. Bacteraemia due to 'viridans' streptococci was documented in 64% of cases and the organisms were first detected as fever developed and mucositis approached its peak. The WHO scheme defined mucositis as either absent or grade 3-4 corresponding to a DMS of 4 or 5, whereas a grading system based on the most pronounced sign or symptom resulted in three grades of severity which corresponded to a DMS of less than or equal to 4, 5-9 and greater than or equal to 10 respectively. However, only the DMS permitted monitoring of mucositis through all its stages of development. The scheme therefore offers the potential for exploring causal relationships between mucosal damage, granulocytopenia, fever and bacteraemia and can be included as an independent measure in studies of prevention and therapy of complications related to mucositis. PMID- 1628124 TI - Liver disease in patients with liver dysfunction prior to bone marrow transplantation. AB - Twenty-two patients with previous hepatic compromise who underwent allogeneic bone marrow transplant (BMT) for treatment of hematologic malignancy or other hematologic disease between 1984 and 1990 were chosen for the present study. After transplant, 19 (86.4%) of the patients developed hepatitis, including six cases (27.3%) of acute hepatitis, 12 (54.6%) of chronic hepatitis and one uncharacterized hepatitis. Nine chronic hepatitis patients were followed-up for 7 56.5 months (medium 35.5 months) with biochemistry studies and ultrasonography. Throughout the observation period, liver cirrhosis or hepatoma were not detected and no patients developed veno-occlusive disease. Furthermore patients who developed hepatitis after transplant had worse prognoses. Based on serial serological survey of the various hepatitis B virus (HBV) antigens and antibodies, we have found that most of the recurrent viral hepatitis in transplant patients could be attributed to the reactivation of the virus. In addition, the use of immunosuppressive drugs, persisting infection by HCV and the development of graft-versus-host disease may also play a role in modulating the course of viral hepatitis in BMT patients. PMID- 1628125 TI - The role of recombinant cytokines and other immunomodulators on engraftment following allogeneic bone marrow transplantation in mice. AB - BALB/c mice were conditioned by total body irradiation (TBI) with a suboptimal (475 cGy) or optimal (600 cGy) radiation dose for induction of chimerism subsequent to administration of 10(7) (BALB/c x C57BL/6) F1 (F1) bone marrow cells in order to test whether a variety of recombinant cytokines and other immunomodulators caused positive or negative effects on engraftment at different time intervals post-bone marrow transplantation (BMT). Engraftment in recipient mice conditioned by the minimal dose of TBI permitting 100% induction of chimerism (600 cGy) was not impaired following treatment with recombinant human interleukin 2 (IL2) (10(4) Cetus Units x 3/day i.p.), alpha interferon (alpha IFN) (10(4) units/day i.p.), gamma interferon (gamma IFN) (10(4) U/day i.p.) and combinations of IL2 + alpha IFN as well as IL2 + gamma IFN given either 5 days prior to or 5 days following BMT. Likewise, neither PGE2 (50 micrograms x 2/day i.p.) nor indomethacin (25 micrograms x 2/day i.p.) given either immediately prior to or immediately following BMT for 3 consecutive days had any detectable effect on chimerism. To investigate the putative beneficial effects of IL2 in enhancing marrow engraftment, BALB/c mice were irradiated with a suboptimal dose of TBI (475 cGy) followed by reconstitution with 10(7) F1 marrow cells supplemented with 2 x 10(6) F1 spleen cells. IL2 (10(4) U x 3/day i.p. x 5 days) was administered either prior to TBI, between TBI and BMT, immediately following BMT, or starting 2 weeks post-BMT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628126 TI - Immunity to and immunization against measles, rubella and mumps in patients after autologous bone marrow transplantation. AB - Humoral immunity to measles, rubella and mumps was studied in 63, 36 and 16 patients 1, 2 and 3 years, respectively after autologous bone marrow transplantation (ABMT). Serologic examination was performed using antibody-ELISA. One year after ABMT, 7/57 patients (12%) who were seropositive to measles before ABMT, became seronegative, 8/44 (18%) to rubella and 3/51 (6%) to mumps. Among patients who were retested at 2 and 3 years, three more patients became seronegative to measles, one to rubella, and three to mumps. Nine of 12 children who had previously been immunized against measles were seropositive before ABMT, 3/7 to rubella and 5/7 to mumps, respectively. After ABMT, 5/9 became seronegative to measles, none to rubella and 2/5 to mumps. Six seronegative children were immunized with a live trivalent attenuated measles, mumps, and rubella vaccine 1 to 2 years after ABMT. Two children seroconverted to measles, six to rubella, and four to mumps. No side effects were observed. Most adult patients who have had the diseases of measles, rubella, or mumps naturally remain seropositive, while children who have been immunized commonly lose their immunity after ABMT. PMID- 1628127 TI - Allogeneic bone marrow transplantation for high risk acute lymphoblastic leukemia. Results from a single institution. AB - We present our experience with bone marrow transplantation (BMT) in 30 consecutive patients with high risk acute lymphoblastic leukemia. With a median follow-up of 4 years the disease-free survival (DFS) was 44% for the whole group, with a significant difference between patients in first or second complete remission (CR 1 and 2, as one group), compared with patients with more advanced disease (greater than CR2), 69.5% versus 15.4% (p less than 0.01). The main cause of BMT failure was leukemic relapse, with a relapse rate of 15% for patients in CR 1 and 2 and of 77% for patients with greater than CR2 (p less than 0.01). Among patients with active disease at BMT those who had 15% blast cells or less in the marrow fared better than those with more advanced disease or extramedullary relapse. Transplant-related death was 17%. Graft-versus-host disease (GVHD) was associated with an antileukemic effect; the DFS for patients with acute and/or chronic GVHD was better than for patients with no GVHD at all. PMID- 1628128 TI - Slow response to induction chemotherapy is an indicator of poor survival after bone marrow transplantation for acute lymphoblastic leukemia. The Leukemia Working Party of the European Group of Bone Marrow Transplantation (EBMT). AB - The prognostic value of diagnosis-remission interval on leukemia-free survival (LFS) after bone marrow transplantation (BMT) was investigated retrospectively in 193 adult patients with acute lymphoblastic leukemia (ALL) transplanted in first remission and reported to the EBMT between 1979 and 1986. Patients achieving remission within 8 weeks of diagnosis ('fast responders') had better LFS after BMT than those with remission after 8 weeks ('slow responders'): LFS at 3 years was 43% vs 32% for fast and slow responders, respectively (p = 0.04). The effect on LFS was particularly severe for slow responders transplanted within 3 months of remission. Only 17% of the slow responders with short remission-BMT interval survived at 3 years. Decreased LFS was caused by both excess of transplant related mortality and increased relapse incidence. In a multivariate analysis, time intervals (both diagnosis-remission and remission-BMT) were the strongest independent prognostic factor for LFS, probability of relapse and transplant related mortality. We conclude that the intervals diagnosis-remission and remission-BMT have a strong prognostic value in adult patients with ALL not only for remission duration after conventional treatment, but also for LFS after BMT. PMID- 1628129 TI - A regional autologous bone marrow transplant network: transfers to designated centers on the day after transplant. AB - Autologous bone marrow transplantation (ABMT) is becoming increasingly prevalent for treatment of advanced malignant disease. In order to increase the availability and utility of this therapy, we assessed the feasibility of transferring patients to their regional referral centers on the day after marrow infusion (day 1), for management post-transplant. This prospective study compares the outcome of 77 patients either transferred the day after marrow transplant for subsequent management at one of six selected Canadian regional centers closest to their domicile, or treated entirely at The Toronto Hospital, according to a common protocol. Study end-points included frequency of complications during transfer, transplant-related morbidity and mortality and hematopoietic recovery. Assessment of eligibility for transplant, bone marrow harvesting, autograft cryopreservation, administration of intensive therapy and marrow infusion were conducted in all cases at The Toronto Hospital. Thirty patients received marrow transplants and were transferred on day 1. There were no complications during transfer. Compared with 47 consecutive patients treated entirely at The Toronto Hospital, there were no differences in treatment-related morbidity or mortality, use of intravenous antifungal therapy or total days of hospitalization. We conclude that day 1 transfer of patients after ABMT to designated centers is feasible and safe. The operation of a regional ABMT network appears to benefit patients, relatives, referring physicians, the transplant center and may also improve health care delivery. PMID- 1628130 TI - Use of IgM enriched intravenous immunoglobulin (Pentaglobin) in bone marrow transplantation. AB - In a study of 63 allogeneic and autologous bone marrow transplants, patients were randomized to receive the IgM and IgA enriched intravenous immunoglobulin (IVIG) preparation (Pentaglobin). Pentaglobin has been postulated to have anti-endotoxin properties and one of the aims of the study was to measure endotoxin levels in these patients together with the clinical sequelae of infection. The anti endotoxin effects of Pentaglobin were found to reside in the IgM fraction. Those patients who received Pentaglobin were significantly protected from dying from infection in the first 100 days after the transplant, although it was not actually possible to document bacterial infections as the cause of death in the control patients. Peak endotoxin levels were significantly reduced (p = 0.02) in those patients receiving Pentaglobin. Liver damage as assessed by liver enzyme abnormalities correlated significantly with the presence of endotoxaemia greater than 25 pg/ml and up to 70% of pyrexial episodes were associated with endotoxaemia. Our results suggest that Pentaglobin is useful in reducing hepatic toxicity and this may be related to a reduction in endotoxaemia. PMID- 1628131 TI - Bone marrow harvest for marrow transplantation: effect of multiple small (2 ml) or large (20 ml) aspirates. AB - The aim of this study was to evaluate the yield of nucleated cells and CFU-GM and the T cell composition in bone marrow harvested by means of multiple small (2 ml) or large (20 ml) aspirations. Eleven marrow donors were studied: each donated 1000 ml of bone marrow in two aliquots of 500 ml for an HLA identical sibling transplant. In six cases the first 500 ml were harvested by means of multiple 2 ml aspirations (A) and the second 500 ml by means of 20 ml aspirations (B). In five cases the opposite was done: 20 ml aspirates first (C) and 2 ml afterwards (D). From each 500 ml aliquot a sample was taken for enumeration of nucleated cells and CD3+ lymphocytes and for CFU-GM growth. Small volume aspirations (groups A and D) yielded more nucleated cells (p = 0.02), more CFU-GM (p = 0.03) and fewer CD3+ cells (p = 0.1) when compared with large volume aspirations (groups B and C). This study shows that marrow harvesting by means of multiple small volume aspirations minimizes the dilution with peripheral blood and results in greater numbers of cells and hemopoietic progenitors. PMID- 1628132 TI - Cytokine-induced resistance to microbial infections in normal, immunosuppressed and bone marrow transplanted mice. AB - We studied the efficacy of in vivo and in vitro treatments with IL-1, IL-2, IL-3, and GM-CSF in the protection against bacterial (Salmonella typhimurium), fungal (Candida albicans) and viral (influenza virus A/PR8) infections, of normal, sublethally irradiated and lethally irradiated, bone marrow (BM) reconstituted mice. In parallel, the cytokines were tested for their ability to potentiate hematopoietic activity in vitro and in vivo. We demonstrate that, under the experimental conditions employed, IL-1 had the best protective activity against the three micro-organisms in both normal and immunocompromised mice when administered in vivo. Administration of IL-2 led to increased resistance in normal but not in immunodeficient mice, whereas GM-CSF had no beneficial effects. In contrast, preincubation of BM cells in these cytokines, singly or combined, prior to transplantation to lethally irradiated mice, did not confer protection against subsequent infection, although it increased the number of BM derived CFU GM in culture (except in the case of IL-2). Administration of IL-1 or GM-CSF to BM transplanted mice facilitated WBC recovery, whereas IL-2 delayed it. Collectively, the data suggest that IL-1, alone or combined with other cytokines, may be beneficial in the prevention or treatment of microbial infections in immunocompromised and BM transplanted patients. It can also be concluded that enhanced hematopoietic recovery may not always coincide with the development of resistance to micro-organisms. PMID- 1628133 TI - Interleukin-2 (IL-2) and IL-2-activated bone marrow in transplantation: evaluation from a clinical perspective. AB - Incubation of bone marrow (BM) with interleukin-2 (IL-2) in vitro results in generation of killer cells providing a tool for enhancing the graft-versus-tumor effect in transplantation. We have evaluated the influence of IL-2 on the progenitor cell activity (PCA), homing pattern of BM and hemopoiesis in a syngeneic bone marrow transplantation (BMT) model in mice. The PCA index and homing pattern of BM activated with IL-2 in vitro for 24 h (ABM) were similar to those of fresh bone marrow (FBM). In vitro culture of BM for more than 1 day resulted in progressive decline in its PCA index; this was not related to the presence or absence of IL-2 in the culture medium. Toxicity of IL-2 was related to the dose and not the time of institution of IL-2 therapy after BMT. Maximum tolerated dose of IL-2 instituted immediately after BMT was 10 times higher than the dose in a non-BMT setting. The pattern of marrow reconstitution following BMT with ABM was comparable to that with FBM. This study shows that BMT with BM activated with IL-2 for 24 h results in normal hemopoiesis, and IL-2 therapy instituted immediately after BMT with ABM does not cause additional toxicity. PMID- 1628134 TI - Long-term cryopreservation of human stem cells. AB - Successful engraftment of autologous bone marrow depends on preserving the viability of stem cells during cryopreservation. While several techniques for effective bone marrow and peripheral blood stem cell collection and processing have been reported, little is known about the effect of the duration of cryopreservation on stem cell viability in humans. We reviewed, retrospectively, the engraftment data of 33 patients with leukemia treated at Brigham and Women's Hospital, Boston and the European Bone Marrow Transplant Group from 1981-1989 who received stem cells cryopreserved for greater than or equal to 2 years. Data on cryopreservation methods are available in 18 of 33 patients. In all cases, stem cells were frozen in liquid nitrogen with a programmed freezer and stored at or below -140 degrees C. The median duration of cryopreservation was 2.8 years (range 2-11 years). Thirty of 32 (94%) evaluable patients achieved granulocyte counts greater than 500 x 10(6)/l (median 23 days; range 10-119 days); 26 of 32 (74%) evaluable patients achieved platelets greater than 50 x 10(9)/l (median 30 days; range 19-128 days) while 22/32 (69%) patients achieved platelets greater than 100 x 10(9)/l (median 45 days; range 20-328 days). This report demonstrates that human stem cells cryopreserved for up to 11 years are capable of engrafting. Stem cells may be stored for prolonged periods and used for transplantation in patients harvested prior to pelvic irradiation or alkylating agent therapy. PMID- 1628135 TI - No increase in relapse in patients with myeloid leukaemias receiving rhGM-CSF after allogeneic bone marrow transplantation. AB - Twenty patients with leukaemia received recombinant human GM-CSF (rhGM-CSF) after allogeneic bone marrow transplantation (BMT) in a double blind controlled trial, with a significant promotion of granulopoiesis when compared with 20 control patients. The follow-up in survivors is now sufficiently long to assess the potential for promotion of relapse in the patients with myeloid leukaemias. Six patients with myeloid leukaemias are alive 22-38 months after transplantation. Eight other patients with myeloid leukaemias died within 12 weeks of transplantation without active active disease. None of these 14 patients with myeloid leukaemias have relapsed. This study supports the view that rhGM-CSF does not increase the probability of relapse after allogeneic BMT in patients with myeloid leukaemia. PMID- 1628137 TI - Post-irradiation somnolence syndrome in an adult patient following allogeneic bone marrow transplantation. AB - Neurologic disturbances are common following the intensive chemotherapy and radiotherapy of bone marrow transplantation (BMT) conditioning regimens. The somnolence syndrome, which occurs in most children treated for leukemia with prophylactic cranial irradiation, has previously not been reported following BMT. This syndrome consists of transient lethargy, irritability, headaches, low grade fevers, gastrointestinal disturbances and depression. We report the case of a 38 year-old female with acute non-lymphocytic leukemia who developed symptoms typical of the somnolence syndrome 8 weeks following 1320 cGy total body irradiation and cyclophosphamide conditioning. Encephalographic findings were consistent with the syndrome, and no additional infectious or metabolic disorders could be identified. As predicted by the pediatric experience, the symptoms were transient, resolving following steroid and anti-depressant therapy. Among patients undergoing radiation based conditioning regimens, especially those not receiving concurrent steroid therapy, the appearance of post-transplantation somnolence may be an expression of this syndrome. PMID- 1628136 TI - Late marrow allograft rejection following alpha-interferon therapy for hepatitis in a patient with paroxysmal nocturnal hemoglobinuria. AB - We describe a case of allograft rejection that occurred 23 months after successful bone marrow transplantation for severe aplastic anemia in a patient with paroxysmal nocturnal hemoglobinuria. The allograft rejection appears to have been induced by recombinant alpha-interferon (rINF-alpha) treatment for non-A, non-B hepatitis that developed 11 months after transplantation. During the 9 months of active hepatitis, the donor graft functioned normally; however, 3 months after rINF-alpha therapy was started, pancytopenia and a chimeric hematopoietic state developed. rINF-alpha was discontinued, cyclosporin A was reintroduced, and autologous bone marrow recovery followed. rINF-alpha treatment may be detrimental to some recipients of allogeneic bone marrow transplants. PMID- 1628138 TI - Fracture of the ilium: an unusual complication of bone marrow harvesting. PMID- 1628139 TI - MK801 attenuates behavioural adaptation to chronic nicotine administration in rats. AB - The effect of administering MK801 (0.3 mg kg-1) during chronic nicotine (0.4 mg kg-1) treatment was studied on locomotor activity in rats. Sensitization of the locomotor activity response to nicotine was seen with chronic nicotine treatment. This sensitization was attenuated in rats that had received MK801 30 min before the daily nicotine injections during chronic treatment. These results suggest that the NMDA receptor may be involved in the adaptive processes seen with chronic nicotine administration. PMID- 1628140 TI - ATP modulates the efferent function of capsaicin-sensitive neurones in guinea-pig isolated atria. AB - 1. The effect of adenosine triphosphate (ATP) and its stable analogues, alpha, beta-methylene-ATP and beta, gamma-methylene-ATP, on the efferent function of capsaicin-sensitive non-adrenergic, non-cholinergic (NANC) nerves was tested in guinea-pig isolated atria. 2. Transmural nerve stimulation of atria isolated from reserpine-pretreated guinea-pigs, in the presence of 1 microM atropine and 0.3 microM CGP 20712A, induced a transient positive inotropic effect attributable to calcitonin gene-related peptide (CGRP) release from NANC nerve endings. 3. ATP (1 30 microM) concentration-dependently reduced the cardiac response to transmural nerve stimulation, without affecting the inotropic response to 10 nM exogenous CGRP. The inhibitory effect of ATP was competitively antagonized by the P1 purinoceptor antagonist, 8-phenyltheophylline (8-PT, 1 microM), but was unaffected by the P2-purinoceptor antagonist, suramin (100 microM). 4. beta, gamma-methylene-ATP in the same concentration range as ATP, inhibited the cardiac response to transmural nerve stimulation. The inhibitory effect of beta, gamma methylene ATP was antagonized by 1 microM 8-PT. The desensitizing agonist for P2 purinoceptors, alpha, beta-methylene ATP did not induce any inhibitory effect either on the cardiac response to transmural nerve stimulation or on the inhibitory effect curve for ATP. 5. The inhibitory effect of ATP on the NANC neurotransmission was inconsistently modified in the presence of 10 microM alpha, beta-methylene-adenosine diphosphate, an inhibitor of the 5'-ectonucleotidases. 6. These results demonstrate that ATP modulates the efferent function of cardiac NANC nerve endings through prejunctional inhibitory receptors belonging to the P1 type. The metabolic conversion of ATP to adenosine does not seem to be a pre requisite for the ATP agonist activity. PMID- 1628141 TI - Adenine nucleotide-induced inhibition of binding of sulphonylureas to their receptor in pancreatic islets. AB - 1. The effects of the Mg complex of adenosine 5'-triphosphate (MgATP) on binding of sulphonylureas to microsomes obtained from mouse pancreatic islets were examined. 2. MgATP inhibited the binding of both glibenclamide and tolbutamide to microsomes. 3. Binding of [3H]-glibenclamide inhibited by MgATP was not further diminished by Mg(2+)-bound adenosine 5'-(beta, gamma-imidotriphosphate) (AMP-PNP) or free adenosine 5'-diphosphate (ADP). Higher concentrations of MgAMP-PNP induced a partial reversal of the inhibitory effect of MgATP on [3H] glibenclamide binding. 4. The apparent dissociation constant (K'D) for binding of [3H]- glibenclamide remained constant when 5. Extracellular ADP did not markedly stimulate insulin release from mouse pancreatic islets. 6. It is concluded that sulphonylureas and cytosolic nucleotides exert their inhibitory effects on the K ATP-channels of beta-cells by binding to different sites. The binding properties of the sulphonylurea receptor seem to be modulated by protein phosphorylation. PMID- 1628142 TI - Effects of BRL 38227 on potassium currents in smooth muscle cells isolated from rabbit portal vein and human mesenteric artery. AB - 1. Single smooth muscle cells were isolated from the rabbit portal vein and the human mesenteric artery and whole cell currents recorded at room temperature from either cell type by the whole cell voltage clamp technique. 2. In the rabbit portal vein cells addition of 10 microM BRL 38227 induced a quasi-instantaneous, voltage-insensitive and time-independent current which had a reversal potential of -75 mV under experimental conditions where the calculated EK was -83 mV. 3. Cells were held at 0 mV and BRL 38227 was added cumulatively to construct a dose response relationship. BRL 38227 (0.03-10 microM) caused a dose-dependent outward shift in the holding current with an EC50 of 1.3 microM. 4. BRL 38227 (10 microM) had no effect on the delayed rectifier K+ current measured in the presence of 5 mM tetraethylammonium and no effect on the Ca(2+)-activated K+ current measured in the presence of 5 mM 4-aminopyridine. Similarly BRL 38227 had no effect on the Ca2+ current. 5. The BRL 38227-induced current was blocked by glibenclamide (10 microM) and phentolamine (100 microM), specific blockers of the ATP-sensitive K+ current in single cells. 6. In human isolated mesenteric artery cells, BRL 38227 (10 microM) induced a glibenclamide-sensitive current similar to, but smaller than, that observed in the rabbit portal vein. 7. We conclude that in these cells, BRL 38227 activates a potassium conductance which has the electrophysiological and pharmacological characteristics of ATP-sensitive K+ channels. PMID- 1628143 TI - Effect of sulphur containing amino acids on [3H]-acetylcholine release from amacrine cells of the rabbit retina. AB - 1. The effects of the sulphur containing amino acids, homocysteic acid, homocysteine sulphinic acid, cysteic acid and cysteine sulphinic acid on the release of [3H]-acetylcholine ([3H]-ACh) from the cholinergic amacrine cells of the rabbit retina were examined. 2. All the compounds stimulated the spontaneous resting release and abolished the light-evoked release of [3H]-ACh. Except for homocysteine sulphinic acid these actions occurred at concentrations that did not affect the erg b-wave amplitude, indicating a site of action at the inner retina. 3. N-methyl-D-aspartate (in Mg(2+)-containing medium) clearly blocked the effects of homocysteic acid and homocysteine sulphinic acid on the resting release of [3H]-ACh but had no effect on the actions of cysteic acid and cysteine sulphinic acid. 4. Since N-methyl-D-aspartate is an antagonist of the light-evoked endogenous bipolar cell transmitter released onto cholinergic cells, these results are consistent with the suggestion that homocysteic acid or homocysteine sulphinic acid may be a transmitter released from this subpopulation of bipolar cells. 5. The present experiments indicate the existence of excitatory amino acids that have closer pharmacological properties to a bipolar cell transmitter than glutamate but it remains to be seen whether homocysteic acid or homocysteine sulphinic acid occur in these particular bipolar cells. PMID- 1628144 TI - Different in vivo properties of three new inhibitors of catechol O methyltransferase in the rat. AB - 1. We compared three new catechol O-methyltransferase (COMT) inhibitors (OR-611, Ro 40-7592 and CGP 28014; 10 and 30 mg kg-1, i.p.) in male rats given levodopa (L DOPA, 50 mg kg-1, i.p.) and carbidopa ((-)-L-alpha-methyl dopa, 50 mg kg-1, i.p.). In some studies pretreatment with pargyline (80 mg kg-1, i.p.) was used to block the function of monoamine oxidase (MAO). 2. Decreases of hypothalamic and striatal 3-O-methyl-dopa (3-OMD) levels were used as measures of the inhibition of peripheral COMT. The inhibition of brain COMT activity was estimated by decreases of hypothalamic and striatal homovanillic acid (HVA) and 3 methoxytyramine (3-MT; after pargyline) levels. 3. The three COMT inhibitors studied had different individual characteristics. OR-611 was primarily a peripherally acting COMT inhibitor, decreasing 3-OMD levels in the striatum (to 31-52%) and in the hypothalamus (to 16-27%) both in the control and pargyline treated animals at 1 and 3 h. It did not have any effect on brain HVA and 3-MT. 3. Ro 40-7592 was a broad spectrum COMT inhibitor decreasing striatal and hypothalamic 3-OMD (always to less than 30%), HVA (to less than 50%) and 3-MT levels (to less than 23%) significantly both at 1 and 3 h. It was more potent than OR-611. 4. CGP 28014 functioned as a weak COMT inhibitor in the periphery inhibiting 3-OMD formation only at 3 h. In contrast, it was fairly potent in decreasing the brain HVA and 3-MT levels at 1 h (to 37-22% and 42-35% in the striatum, and to 57-33% and 64-35% in the hypothalamus, respectively) but not at 3 h. Since CGP 28014, unlike OR-611 and Ro 40-7592, did not generally increase the brain DOPA, dopamine or DOPAC levels, it was not a typical COMT inhibitor. PMID- 1628145 TI - Bovine polymorphonuclear leukocytes increase sensitivity to noradrenaline in isolated mesenteric arteries. AB - 1. The effects of polymorphonuclear leukocytes (PMN) on vascular function to (-) noradrenaline were examined in vitro. Purified bovine PMN were incubated in siliconized organ baths containing rings of bovine mesenteric arteries, after which a concentration-effect curve in response to (-)-noradrenaline was obtained. 2. PMN-derived products induced a long lasting concentration-dependent contraction of the blood vessels generating 24.4 +/- 6.8% of the maximal tension to (-)-noradrenaline at a cell concentration of 2.5 x 10(6) ml-1. The contractile response was also found in endothelium-denuded vascular rings. 3. PMN present in the organ bath caused an increase in the sensitivity of vascular rings to (-) noradrenaline. At a cell number of 2.5 x 10(6) PMN ml-1 the pD2-value for (-) noradrenaline was augmented 0.40 +/- 0.05 (P less than 0.001), while total contraction at the highest concentration (-)-noradrenaline was not affected. This increase in sensitivity was dependent on an intact endothelium. 4. The increase in sensitivity to (-)-noradrenaline by PMN was inhibited by superoxide dismutase, but not by catalase, dimethylthiourea, indomethacin or nordihydroguaiaretic acid. The non-stimulated bovine PMN produced oxygen radicals as measured by chemiluminescence. 5. Simultaneous incubation of PMN and (-)-noradrenaline with arterial rings induced an increase in the release of prostacyclin, measured by an elevated concentration of 6-keto-prostaglandin F1 alpha in the supernatant. 6. It is concluded that PMN can increase vascular tone directly or indirectly probably via the interaction of PMN-derived superoxide anions with endothelium-derived relaxing factor. PMID- 1628146 TI - CI988, a selective antagonist of cholecystokininB receptors, prevents morphine tolerance in the rat. AB - 1. The effect of chronic treatment with CI988, a recently developed selective antagonist of cholecystokinin type-B receptors (CCKB receptors) on the tolerance to morphine analgesia was studied in rats with the hot plate test. 2. Morphine tolerance was induced with the use of two paradigms. Morphine was injected i.p. either in a schedule of increasing doses (1-32 mg kg-1) twice daily for 6 days or at a fixed dose (3 mg kg-1) daily for 29 days. 3. In both series of experiments, tolerance to the analgesic effect of morphine was prevented by simultaneous treatment with i.p. CI988. Chronic treatment with only CI988 daily for up to 29 days did not reduce the analgesic effect of a weekly injection of morphine. 4. CI988 did not diminish the physical dependence to morphine, as examined with naloxone precipitated withdrawal. 5. The present results provide evidence that chronic treatment with a selective CCKB receptor antagonist could prevent tolerance to the analgesic effect of morphine without affecting morphine-induced physical dependence. Application of CCK antagonists may be clinically important in treating chronic pain patients by preventing morphine tolerance and by eliminating the need to increase morphine doses to unacceptable levels. PMID- 1628147 TI - Comparisons of the effects of ryanodine on catecholamine secretion evoked by caffeine and acetylcholine in perfused adrenal glands of the guinea-pig. AB - 1. The effect of ryanodine on catecholamine secretion induced by caffeine and muscarinic receptor activation was investigated in perfused adrenal glands of the guinea-pig. 2. Caffeine (40 mM) caused only a small increase in catecholamine secretion during perfusion with standard Locke solution. Caffeine-induced catecholamine secretion was markedly enhanced after removal of CaCl2 together with replacement of NaCl with sucrose. 3. In the absence of CaCl2 and NaCl, 50 microM ryanodine had no effect on the resting catecholamine secretion. Caffeine (40 mM) administered 15 min after treatment with ryanodine caused an increase in catecholamine secretion similar to that prior to application of ryanodine, but failed to have any effect thereafter. Combined application of ryanodine and caffeine also prevented catecholamine secretion induced by caffeine applied subsequently. 4. Catecholamine secretion induced by 100 microM acetylcholine (ACh) was only partially inhibited after treatment with ryanodine plus caffeine under Ca(2+)-free, Na(+)-deficient conditions. 5. Preferential influence of ryanodine on the response to caffeine was also confirmed in catecholamine secretion evoked by paired stimuli with caffeine and ACh alternately, during perfusion with either Ca(2+)-free Locke or sucrose-substituted solutions. 6. These results indicate that caffeine increases catecholamine secretion by mobilizing Ca2+ from intracellular Ca2+ stores through ryanodine-sensitive mechanisms in guinea-pig adrenal chromaffin cells. Ca2+ stores sensitive to caffeine and muscarinic receptor activation may not overlap entirely. PMID- 1628148 TI - The effect of lipopolysaccharide, interleukin-1 and tumour necrosis factor on the hepatic accumulation of 5-hydroxytryptamine and platelets in the mouse. AB - 1. Injection of lipopolysaccharide (LPS; 0.5-500 microgram kg-1) into mice induced a dose-dependent, slowly developing increase in hepatic content of 5 hydroxytryptamine (5-HT). This sustained increase could not be attributed to an LPS-induced alteration of the pharmacokinetic handling of 5-HT by stimulation of its uptake or inhibition of its degradation. 2. Regional differences were apparent in the tissue content of histamine and 5-HT between mast cell-deficient (W/Wv) and normal (+/+) mice. LPS administration (0.5 mg kg-1) gave comparable increases in the hepatic level of 5-HT in mast cell-deficient and normal mice. 3. Reserpine pretreatment (1 mg kg-1) selectively reduced 5-HT levels in the blood, spleen, liver, brain and lung of normal mice. Prior treatment with this agent also abolished the LPS (0.5 mg kg-1)-induced hepatic accumulation of 5-HT. 4. Accumulation of 5-HT in the liver by LPS (0.1 mg kg-1) was temporally associated with both a fall in the levels of circulating platelets, and a reduction in the concentration of 5-HT in the blood. The LPS dose-dependent (0.5-500 micrograms kg 1) increase in hepatic 5-HT content was associated with a similar dose-dependent reduction in the circulating levels of 5-HT. 5. Interleukin-1, alpha and beta (10 micrograms kg-1) and tumour necrosis factor alpha (TNF alpha) (1 mg kg-1) significantly enhanced the accumulation of 5-HT within the liver. Administration of TNF alpha (10 micrograms kg-1) potentiated the increase in hepatic 5-HT content seen with IL-1 beta (10 micrograms kg-1). 6. Electron microscopy revealed numerous platelets in the sinusoidal and perisinusoidal Disse spaces within the liver, in animals pretreated with LPS (0.1 mg kg '). The platelets retained their intact structure and showed no evidence of degranulation. 7. These data suggest that the LPS and cytokine-induced mobilization of 5-HT in the liver is associated with the hepatic translocation of platelets. This migration appears to be independent of platelet aggregation. PMID- 1628149 TI - Okadaic acid inhibits activation of phospholipase C in human platelets by mimicking the actions of protein kinases A and C. AB - 1. The effect of okadaic acid, a potent inhibitor of protein phosphatases 1 and 2A (PP1 and PP2A), on human platelets has been investigated. 2. Okadaic acid exerts a general increase in phosphorylation of platelet proteins but did not induce aggregation or secretion of 5-hydroxytryptamine (5-HT). Okadaic acid, however, did inhibit thrombin-induced functional responses. 3. Maximally effective concentrations of prostacyclin, to elevate adenosine 3'-5'-cyclic monophosphate (cyclic AMP), or phorbol dibutyrate, to activate protein kinase C, inhibited the formation of inositol phosphates by thrombin by approximately 60%. When used in combination, prostacyclin and phorbol dibutyrate reduced the levels of inositol phosphates induced by thrombin to 11%. 4. Okadaic acid (1 microM) decreased thrombin-induced formation of inositol phosphates by approximately 55% and increased the inhibitory action of prostacyclin or phorbol dibutyrate. Okadaic acid had no further effect when prostacyclin and phorbol dibutyrate were used in combination. 5. These results suggest that protein kinases A and C act to inhibit phospholipase C by distinct mechanisms and that their action is reversed by PP1 and/or PP2A. PMID- 1628150 TI - Increased secretion of glandular-kallikrein in the bronchial washings induced by intravenous injection of leukotriene C4 in guinea-pigs. AB - 1. Intravenous administration of leukotriene C4 (LTC4) and LTD4 (1-10 nmol kg-1) caused a dose-dependent increase in secretion of glandular-kallikrein in the bronchial washings of guinea-pigs, as measured by cleavage of a synthetic substrate and the formation of kinin. LTC4 was more potent than LTD4 and pilocarpine was much less potent than peptide leukotrienes on a molecular basis. 2. The increases in levels of glandular-kallikrein in the bronchial washings that were induced by LTC4 (3 nmol kg-1, i.v.) were almost completely inhibited by pretreatment with an antagonist of leukotrienes (ONO-1078), with an antagonist of thromboxane (S-1452), with an inhibitor of thromboxane synthetase (OKY-046), with indomethacin, with atropine or with scopolamine. These results indicate that the LTC4-induced increase in levels of glandular-kallikrein may have been mediated by the formation of thromboxane and the release of acetylcholine. 3. The increases in levels of glandular-kallikrein in the bronchial washings induced by STA2 (20 pmol kg-1, i.v.), a stable analogue of thromboxane A2, were completely blocked by pretreatment with atropine, whereas increases induced by pilocarpine (41 mumol kg 1, i.v.) were not blocked by pretreatment with indomethacin, although such increases were inhibited by atropine. This result indicates that secretion of kallikrein stimulated by LTC4 may have been mediated by the successive formation of thromboxane A2 and release of acetylcholine. 4. Intravenous administration of bradykinin (3-30 nmol kg-1) caused a dose-dependent increase in levels of glandular-kallikrein in the bronchial washings. This increase was completely inhibited by pretreatment with atropine, with indomethacin or with an antagonist of thromboxane.5. The increases in levels of glandular-kallikrein in the bronchial washings induced by LTC4 (3 nmol kg'- , i.v.) and pilocarpine (41 flmol kg- 1, i.v.) were significantly inhibited by pretreatment with an antagonist of bradykinin. These results suggest that intravenous LTC4 may increase secretion of glandular-kallikrein via formation of thromboxane A2 and release of acetylcholine in that order, and kinin released by kallikrein may enhance the rate of secretion of glandular-kallikrein. PMID- 1628151 TI - Characterization of P1-purinoceptors on rat duodenum and urinary bladder. AB - 1. The P1-purinoceptors mediating relaxation of the rat duodenum and inhibition of contraction of the rat urinary bladder were characterized by use of adenosine and its analogues 5'-N-ethylcarboxamidoadenosine (NECA), N6-cyclopentyladenosine (CPA) and 2-p-((carboxyethyl)phenethylamino)-5'- carboxamidoadenosine (CGS 21680), as well as the A1-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). The stable analogue of adenosine 5'-triphosphate (ATP), adenylyl 5' (beta,gamma-methylene)diphosphonate (AMPPCP), was also used as previous work had indicated that it has a direct action on some P1 receptors in addition to its P2 purinoceptor activity. 2. In the rat duodenum, the order of potency of the adenosine agonists was NECA greater than or equal to CPA greater than AMPPCP = adenosine greater than CGS 21680, and DPCPX antagonized CPA and AMPPCP at a concentration of 1 nM whereas equivalent antagonism of NECA and adenosine required a concentration of 1 microM. This suggests the presence of a mixture of A1 and A2 receptors in this tissue, with CPA and AMPPCP acting on the A1 and NECA and adenosine acting on the A2 receptors. 3. In the rat bladder, the order of potency of the adenosine agonists for inhibition of carbachol-induced contractions was NECA much greater than adenosine greater than CPA = CGS 21680, and a concentration of DPCPX of 1 microM was required to antagonize responses to NECA and adenosine. This suggests the presence of A2 receptors in this tissue. ATP and AMPPCP each caused contractions which were not enhanced by DPCPX (1 microM) which suggests that in this tissue AMPPCP was acting only via P2 receptors and had no P1 agonist activity. That AMPPCP was active on the A1 receptors in the duodenum but inactive on the A2 receptors in the bladder implies that it has selectivity for the A1 subtype.4. That CGS 21680, which has been reported to bind selectively to the high affinity A2a subclass of A2 receptors, had a very low potency on the A2 receptors in the duodenum and in the bladder suggests that these receptors are of the low affinity A2b subclass. PMID- 1628153 TI - The influence of atropine and atenolol on the cardiac haemodynamic effects of NG nitro-L-arginine methyl ester in conscious, Long Evans rats. AB - 1. In the present study, the extent to which baroreflexes contribute to the cardiac effects of NG-nitro-L-arginine methyl ester (L-NAME) was assessed in conscious, Long Evans rats chronically instrumented with thoracic electromagnetic flow probes for the measurement of cardiac haemodynamics. 2. L-NAME (10 mg kg-1, i.v.) was administered in the absence (n = 6) and in the presence (n = 7) of atropine (1 mg kg-1) and atenolol (1 mg kg-1). 3. L-NAME caused a marked increase in mean arterial pressure and marked reductions in total peripheral conductance, cardiac output, heart rate, stroke volume, peak thoracic flow and the maximum rate of rise of aortic flow. 4. Administration of atropine, after the maximal bradycardic effect of L-NAME was established, restored the heart rate to resting levels. Concurrently, there was a reduction in stroke volume, such that cardiac output, although transiently elevated, did not show a sustained increase. No other variables were significantly affected by atropine. Additional administration of atenolol had no effect other than to cause a slight bradycardia, such that in the presence of atropine and atenolol, heart rate was not different from that in animals receiving atropine and atenolol before L-NAME. 5. In the presence of atropine and atenolol, L-NAME had similar pressor, vasoconstrictor and cardiac haemodynamic effects to those in untreated animals, although the bradycardia was significantly attenuated. However, there was still a significant reduction in heart rate following L-NAME in the presence of atropine and atenolol.6. These results indicate that the major component of the bradycardia following L-NAME is indirect and mediated through an increase in vagal efferent activity. However, the substantial reduction in cardiac function caused by L-NAME is not dependent on the autonomic control of the heart but rather, may depend on the increase in afterload and/or a direct effect of L-NAME on the heart and/or its vasculature. PMID- 1628152 TI - Inhibition of endothelium-dependent vasorelaxation by arginine analogues: a pharmacological analysis of agonist and tissue dependence. AB - 1. Isolated rings of rabbit external jugular vein (RbJV) and rat thoracic aorta (RA) were used to study the effect of the NO synthase inhibitor L-NG nitroarginine methyl ester (L-NAME) on muscarinic and 5-hydroxytryptamine (5-HT) receptor-stimulated, endothelium-dependent vascular relaxations. 2. In RbJV relaxations produced by the endothelial 5-HT receptor agonist alpha-methyl-5-HT were potently and non-surmountably inhibited by L-NAME (10 microM), whereas acetylcholine relaxations in this tissue were unaffected by this concentration of inhibitor. By contrast, acetylcholine relaxations in RA were virtually abolished by 10 microM L-NAME. In each case an equivalent concentration of D-NAME was without effect on agonist-induced relaxations. 3. The different effect of L-NAME on acetylcholine relaxations in RbJV and RA was not due to muscarinic receptor differences. Affinity estimates for acetylcholine (pKA = 6.12 +/- 0.09; 6.09 +/- 0.08 respectively) and for 4-diphenyl-acetoxy-N-methylpiperidine methobromide (4 DAMP, pKB = 9.01 +2- 0.012; 9.24 +/- 0.16 respectively) indicated that the receptors in both tissues belong to the same M3 class. Tissue differences resulting from the release of a cyclo-oxygenase product or a glibenclamide sensitive K(+)-channel-linked hyperpolarizing factor were also ruled out by selective inhibition of these pathways. 4. When phenoxybenzamine was used to reduce the efficacy of acetylcholine in RbJV so that it behaved as a partial agonist in this tissue, L-NAME (10 microM) now produced non-surmountable inhibition of relaxation responses. In untreated tissues the same concentration of L-NAME also profoundly inhibited responses produced by butyrylcholine and pilocarpine, both of which behave as partial agonists at the M3 receptor in RbJV. 5. A simple model was developed which describes the theoretical behaviour of receptor-stimulated synthesis and release of NO. The model predicts that competitive inhibition of NO formation results in parallel displacements of the agonist response curve in the case of high efficacy agonist, but right-shift with concomitant depression of the curve maximum in the case of low efficacy agonists. Simulations based on the model showed reasonable agreement with the experimental data. 6. It is concluded that analogues of L-arginine demonstrate tissue- and agonist-dependence in terms of their ability to inhibit receptor-mediated events involving the liberation of NO. This behaviour can reflect differences in agonist efficacy in the receptor systems being studied, a possibility that should be ruled out before apparent resistance to inhibition is taken as evidence for the involvement of heterogeneous endothelium-derived relaxing factors (EDRFs). PMID- 1628154 TI - Sustained decreases in weight and serum insulin, glucose, triacylglycerol and cholesterol in JCR:LA-corpulent rats treated with D-fenfluramine. AB - 1. The effects of D-fenfluramine were studied in the JCR:LA-corpulent rat that is grossly obese, hyperphagic, hyperlipidaemic, hyperinsulinaemic and atherosclerosis-prone. 2. Daily doses of 1, 2.5 and 5 mg kg-1 of D-fenfluramine produced sustained decreases in body weight and food intake over a period of 30 days in 6 month old female rats fed ad libitum. This was accompanied by decreases in the circulating concentrations of glucose, triacylglycerol, free cholesterol and insulin. 3. Food restriction imposed by meal feeding also decreased circulating glucose, triacylglycerols, cholesterol and insulin and diminished the effect of D-fenfluramine on these parameters in male and female rats. 4. Addition of D-fenfluramine to drinking water to give a dose of about 0.25 mg kg-1 daily produced a sustained decrease in body weight and food intake of male and female rats over a nine week period. 5. The results show that the JCR:LA-corpulent rat is very sensitive to the pharmacological effects of D-fenfluramine. These rats should provide an appropriate animal model for determining the mechanisms of action of this anti-obesity agent and whether apparently beneficial changes in metabolism translate into long-term protection against premature atherosclerosis. PMID- 1628155 TI - Pharmacological characterization of angiotensin-induced depolarizations of rat superior cervical ganglion in vitro. AB - 1. The depolarizing responses to angiotensin II and angiotensin III of the rat superior cervical ganglion have been characterized in vitro, by the use of peptidase inhibitors, peptide and non-peptide antagonists and dithiothreitol (DTT). 2. Angiotensin II and III depolarized the ganglion in a concentration related manner. Angiotensin II was approximately 30 fold more potent than angiotensin III. 3. The endopeptidase inhibitor, bacitracin, increased the potency of angiotensin II and III by approximately 4 and 20 fold respectively. The aminopeptidase inhibitor, amastatin, further increased the potency of angiotensin III (but not angiotensin II) by approximately 4 fold. In the presence of bacitracin and amastatin, angiotensin II and III were equipotent. 4. The peptide antagonist [Ile7]angiotensin III (0.01-0.3 microM) produced a non parallel rightward displacement of the angiotensin II concentration-response curve, with a suppression of the maximum response. The potency of [Ile7]angiotensin III was increased by bacitracin and amastatin. 5. The AT1 selective non-peptide antagonist losartan (DuP 753; 0.03 and 0.1 microM) produced a parallel rightward displacement of the angiotensin II concentration-response curve, with an apparent pKB of 8.3 +/- 0.1. A higher concentration of losartan (0.3 microM) depressed the maximum agonist response by 32 +/- 6.5%, possibly reflecting non-competitive behaviour of the antagonist. The potency of losartan was not influenced by bacitracin. 6. The AT2-selective non-peptide antagonist, PD123177 (3 microM) failed to antagonize the angiotensin II-induced depolarizations. 7. DTT (1 mM) produced a 22% reduction of the maximum response to angiotensin II.8. We conclude that the angiotensin II-induced depolarizations of the rat superior cervical ganglion are mediated by angiotensin II receptors of the AT1 subclass. The ability of peptidase inhibitors to modify the potency of peptide agonists and antagonists highlights the difficulties associated with the use of peptide agents to characterize angiotensin II receptors in this preparation. PMID- 1628156 TI - Dopamine release and metabolism in the rat frontal cortex, nucleus accumbens, and striatum: a comparison of acute clozapine and haloperidol. AB - 1. The effects of the typical and typical neuroleptic agents clozapine (CLZ) (2.5 20 mg kg-1, i.p.) and haloperidol (Hal) (0.05-1.0 mg kg-1), were compared on dopamine release and metabolism in the rat prefrontal cortex (PFC), nucleus accumbens (ACC) and striatum (ST). Dopamine release was estimated by measuring the steady-state concentration of 3-methoxytyramine (3-MT) and the level of 3-MT 10 min after pargyline (3-MT accumulation); dopamine metabolism was evaluated from the steady-state concentrations of its acidic metabolites. 2. Both drugs increased 3-MT accumulation in the PFC in a dose-dependent manner. In contrast to Hal, CLZ failed to increase 3-MT accumulation in the ACC or ST. The ST was the region most sensitive to Hal in terms of 3-MT accumulation and, by inference, dopamine release. 3. Both CLZ and Hal dose-dependently elevated the concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in all 3 brain regions studied. The ACC appears to be the region most sensitive to these drugs in terms of changes in the levels of HVA. 4. The result of the present investigations suggest measurements of 3-MT production in the 3 brain regions analysed might be a useful and simple pharmacological tool in the search for atypical neuroleptic drugs with a selectivity of action for the cortical systems. PMID- 1628157 TI - Participation of endothelium-derived nitric oxide but not prostacyclin in the gastric mucosal hyperaemia due to acid back-diffusion. AB - 1. The possible participation of prostacyclin and nitric oxide (NO) in the gastric mucosal hyperaemic response to acid back-diffusion through a disrupted gastric mucosal barrier was examined. The experiments were carried out on anaesthetized rats in which acid back-diffusion was elicited by gastric perfusion with dilute ethanol in 0.15 M HCl and gastric mucosal blood flow (MBF) was measured by the hydrogen gas clearance technique. 2. Indomethacin (28 mumols kg 1, s.c.), an inhibitor of the formation of cyclo-oxygenase products including prostacyclin, failed to alter mean arterial blood pressure (MAP), basal MBF and the hyperaemic response to acid back-diffusion in urethane-anaesthetized rats. 3. NG-nitro-L-arginine methyl ester (L-NAME; 13 and 43 mumols kg-1, i.v.), an inhibitor of endothelium-derived NO formation, increased MAP in a dose-dependent manner. Whilst basal MBF in urethane-anaesthetized rats was not changed, the increase in MBF caused by gastric perfusion with dilute ethanol in acid was dose dependently depressed by L-NAME. The loss of H+ ions from the gastric lumen, an indirect measure of acid back-diffusion, was significantly enhanced by 43 mumols kg-1 L-NAME. In contrast, D-NAME (13 and 43 mumols kg-1) was without effect on MAP, basal and stimulated MBF, and acid back-diffusion. 4. Unlike in urethane anaesthetized rats, L-NAME led to a significant reduction of basal MBF in phenobarbitone-anaesthetized rats. MAP in the phenobarbitone-anaesthetized rats was significantly higher than in urethane-anaesthetized rats, and the hypertensive effect of L-NAME under phenobarbitone anaesthesia was significantly smaller than under urethane anaesthesia.5. The rise in MBF brought about by acid back-diffusion was blocked by L-NAME administered to phenobarbitone-anaesthetized rats. Infusion of L-arginine (120 pmol kg -1 min- ', i.v.) led to a partial, but significant, reversal of the effects of L-NAME on MAP and the hyperaemia due to acid back-diffusion.6. These findings indicate that endothelium-derived NO plays an important mediator role in the gastric mucosal vasodilatation caused by back diffusion whilst vasodilator prostanoids such as prostacyclin are not involved. PMID- 1628158 TI - Effects of pinacidil on guinea-pig isolated perfused heart with particular reference to the proarrhythmic effect. AB - 1. The effects of pinacidil (10, 30, 50 microM) on contractility (+dP/dtmax), coronary perfusion pressure (cP), and ECG intervals (PR, QRS, QT) have been studied on constant-flow perfused guinea-pig hearts, driven at four frequencies (2.5, 3, 3.5, 4 Hz). 2. Pinacidil decreased +dP/dtmax, cP and the QT interval in a dose-dependent manner, whereas the PR interval was increased. QRS duration was not modified. All these effects were independent of driving frequency. Pinacidil decreased the interval from Q-wave to T-wave peak (QTpeak) to a greater extent than the QT interval, thus decreasing the QTpeak/QT ratio. This effect, unlike that on QT interval, was more evident at the highest frequency of stimulation. 3. In 4 out of 20 hearts treated with pinacidil sustained ventricular fibrillation (VF) occurred following a short run of premature ventricular beats (R on T phenomenon). 4. In separate experiments, an attempt to induce VF electrically was made at drug concentrations ranging from 10 microM to 100 microM (8 experiments for each concentration). In control conditions and at the lowest concentrations of pinacidil tested (10 microM) VF could never be induced; in the presence of 30 microM pinacidil VF was induced in 5 out of 8 experiments. Drug concentrations higher than 50 microM permitted the induction of VF in every case. 5. Although the concentrations of pinacidil producing ventricular fibrillation are 30-40 times higher than those found in patients under long term treatment with this agent, it is suggested that caution should be used in prescribing this drug, at least in patients suffering from myocardial ischaemia. PMID- 1628159 TI - Anpirtoline, a novel, highly potent 5-HT1B receptor agonist with antinociceptive/antidepressant-like actions in rodents. AB - 1. The purpose of the present study was to relate the effects of the novel drug, anpirtoline, on 5-hydroxytryptamine (5-HT) receptor subtypes to its antinociceptive and antidepressant-like actions in rodents. 2. Binding assays with rat brain membranes have shown that anpirtoline bound with a much higher affinity to 5-HT1B receptor (Ki = 28 nM) than to 5-HT1A (Ki = 150 nM) and 5-HT2 (Ki = 1.49 microM) receptors. 3. Like 5-HT, anpirtoline concentration-dependently inhibited forskolin-stimulated adenylate cyclase activity in homogenates from the rat substantia nigra. Both effects were not additive, and could be prevented by 5 HT1B receptor antagonists such as propranolol and penbutolol. 4. In superfused rat and pig brain cortex slices preincubated with [3H]-5-HT, the electrically evoked tritium overflow was inhibited by anpirtoline and 5-HT. Whereas 5-HT was equipotent in both tissues (EC50 = 69 nM), anpirtoline was markedly less potent in pig brain cortex slices (EC50 = 1190 nM) than in rat brain cortex slices (EC50 = 55 nM). The concentration-response curve for anpirtoline was shifted to the right by metitepine in both preparations. 5. In the social behaviour deficit test, anpirtoline and trifluoromethylphenyl-piperazine were effective in reversing the isolation-induced impairments in mice, an effect shown only by compounds with agonist properties at the 5-HT1B receptor. 6. In the electrostimulated pain test using mice, anpirtoline dose-dependently increased the pain threshold with an ED50 of 0.52 mg kg-1, i.p. The antinociceptive activity of anpirtoline was abolished by pretreatment with cyproheptadine or propranolol.7. In the forced swimming test in rats, anpirtoline induced a dose related increase in swimming activity. With an ED50 value of 4.6mgkg-1, i.p., anpirtoline was 4 times more potent than the two standard compounds imipramine and desipramine. The decrease of immobility time or the increase of active periods in this model of behavioural despair is suggested to be characteristic of antidepressant drugs.8. Anpirtoline exhibits both antinociceptive and antidepressant-like activities in animals. It is probable that anpirtoline elicits these pharmacological effects via its agonist effect on 5-HT1B and 5-HT1A receptors. PMID- 1628161 TI - Platelet-activating factor (PAF) plays an important role in the immediate asthmatic response in guinea-pig by augmenting the response to histamine. AB - 1. To investigate the role of platelet activating factor (PAF) in the immediate asthmatic response, we examined the bronchial reactivity to histamine after administration of PAF to guinea-pigs or antigen challenge to passively sensitized guinea-pigs. 2. A bolus injection of PAF (20-40 ng kg-1), which did not cause a significant increase in intrathoracic pressure (ITP), augmented the bronchial response to histamine almost 8 fold. This airway hyperreactivity was observed even 1 min after PAF treatment. 3. A subthreshold dose of antigen (0.01 mg kg-1, i.v.) also provoked hyperreactivity to histamine, which became significant 6 and 11 min after the antigen treatment. 4. The specific PAF-antagonists, SM-10661 and CV-6209 (i.v.) dose-dependently inhibited both PAF- and antigen-induced airway hyperreactivities to histamine. 5. These results suggest that PAF plays an important role in antigen-induced acute airway responses by augmenting the activities of spasmogens. PMID- 1628160 TI - The role of nitric oxide in the regional vasodilator effects of endothelin-1 in the rat. AB - 1. The role of nitic oxide (NO) derived from L-arginine in the regional vasodilator effects of endothelin-1 has been investigated in anaesthetized, spontaneously hypertensive (SH) rats in which autonomic reflexes were abolished by ganglion blockade. The experimental design incorporated animals infused with phenylephrine to mimic the peripheral vasconstrictor effects of the NO biosynthesis inhibitors and a single dose per animal paradigm to obviate problems of tachyphylaxis to the vasodilator effects of endothelin-1. 2. Infusion of the inhibitor of NO synthase, N-monomethyl-L-arginine (L-NMMA) at a dose (5 mg kg-1 min-1) which maximally raised blood pressure did not influence either the fall in blood pressure or the vasodilator responses induced in the hindquarters and carotid vascular beds by endothelin-1 (1 nmol kg-1, i.v.) The duration (but not the initial magnitude) of the vasodepressor response to endothelin-1 was however significantly attenuated (by 49%) during infusion of the more potent inhibitor of NO synthase, NG-nitro-L-arginine methyl ester (L-NAME), 2 mg kg-1 min-1. 3. Increasing the dose of L-NAME to 10 and 25 mg kg-1min-1 significantly attenuated, but did not abolish, the falls in blood pressure and hindquarters vasodilator responses to acetylcholine, 1 microgram kg-1, and endothelin-1, 1 nmol kg-1 min 1. The effects were selective in that vasodepressor responses to the endothelium independent vasodilator, sodium nitroprusside, 1-10 micrograms kg-1 min-1, were unaltered. The effects were selective in that vasodepressor responses to the endothelium-independent vasodilator, sodium nitroprusside, 1-l0mg kg min , were unaltered.4. The data indicate that NO generated de novo from L-arginine mediates a significant component of the vasodilator effect of endothelin-1 in the anaesthetized, ganglion-blocked SH rat. However, a major component of the vasodepressor effects of both endothelin-1 and acetylcholine may occur independently of this mechanism. PMID- 1628162 TI - The synovial lining cells in chronic arthritis. PMID- 1628163 TI - Non-steroidal drug-induced peptic ulceration can we really protect the stomach? PMID- 1628164 TI - Intermittent hydrostatic compressive force stimulates exclusively the proteoglycan synthesis of osteoarthritic human cartilage. AB - In paired observations the in vitro proteoglycan turnover was studied of human normal and osteoarthritic cartilage in the absence and presence of intermittent hydrostatic compressive force. Shortly after collection, osteoarthritic cartilage showed a higher proteoglycan synthesis rate than normal cartilage, whereas after culture the reverse was found. Exposure during culture to hydrostatic intermittent compression of a low physiological magnitude enhanced the proteoglycan synthesis rate for osteoarthritic cartilage, whereas normal was unaffected by this hydrostatic intermittent compression. This enhancing effect was reversible. We conclude that human osteoarthritic cartilage is in vivo synthetically more active than normal cartilage, but loses this increased activity in vitro. Enhanced sensitivity of osteoarthritic cartilage to compressive forces may contribute to the increased proteoglycan synthesis of osteoarthritic cartilage. PMID- 1628165 TI - The effect of non-steroidal anti-inflammatory drugs on faecal flora and bacterial antibody levels in rheumatoid arthritis. AB - The faecal flora and bacterial antibody levels of 22 patients with active rheumatoid arthritis (RA) were compared with those of 26 patients with osteoarthritis (OA) undergoing comparable treatment with non-steroidal anti inflammatory drugs (NSAIDs), and a further 22 patients with OA who were not receiving NSAIDs. Faecal counts of Clostridium perfringens were significantly higher in the RA patient group and in those OA patients receiving NSAIDs, compared with those OA patients not taking NSAIDs (P = 0.032, P = 0.0004 respectively). Total aerobic and anaerobic counts were, however, identical in all three groups. Levels of serum IgA antibody to the alpha toxin of Cl. perfringens were higher in the RA group and in the OA group taking NSAIDs than in OA patients not taking NSAIDs (P = 0.011, P = 0.055). Serum IgG antibody to alpha toxin was higher in the RA group than in OA patients both on and off NSAIDs (P = 0.019, P = 0.0072) and also a group of normal controls (P = 0.032). These results suggest that the increased faecal counts of Cl. perfringens together with the associated increased antibody levels seen in this and previous studies are more likely to result from NSAID therapy used to treat the disease than from a disease specific change in bowel flora. PMID- 1628166 TI - Genetic factors influencing the outcome of early arthritis--the role of sulphoxidation status. AB - A minority of individuals have an impaired ability to oxidize sulphur. An increased prevalence of this poor S-oxidation capacity has been observed in patients with established rheumatoid arthritis (RA). The role of this enzyme system in the development of disease was studied by testing the S-oxidation capacity of 54 patients with recent onset symmetrical poly-arthritis, who were followed up at 1 and 4 years. Those patients with persistent disease at 1 year had a prevalence of poor S-oxidation of 69%. At 4 years 74% of those with a diagnosis of RA were poor S-oxidizers compared to 31% of those who were asymptomatic (P less than 0.01). A defective ability to oxidize sulphur appears to predispose to persistent clinical disease. PMID- 1628167 TI - Anticardiolipin antibodies, haemolytic anaemia and thrombocytopenia in systemic lupus erythematosus. AB - Anticardiolipin antibody (ACA) levels were determined in 17 Asian female SLE patients with autoimmune haemolytic anaemia (AIHA) and 29 Asian female SLE inpatients without AIHA (control patients). Both IgG and IgM isotypes were measured by ELISA. Elevated IgM APA titres (greater than 5 SD of normal health controls) were seen in 11 (64.7%) of 17 AIHA patients and six (20.7%) of 29 control patients (P less than 0.01). There was no significant difference in IgG ACA titres between the two groups. Thrombocytopenia was present in 11 (64.7%) of the AIHA patients and nine (31%) of the control patients (P less than 0.05). None of the control SLE patients with thrombocytopenia had raised IgM ACA levels and only one had an elevated IgG ACA titre. Autoimmune haemolytic anaemia occurring in the context of SLE frequently associated with the concomitant presence of thrombocytopenia (Evan's syndrome) and with the presence of ACA. PMID- 1628168 TI - Reliability of skin involvement measures in scleroderma. The UK Scleroderma Study Group. AB - Two methods have been proposed to quantify the extent of skin involvement in scleroderma. These are (1) a scoring system which quantifies and summates this severity rating in 17 areas of skin surface and (2) a method estimating the percentage of skin involvement using a shaded manikin. We report on a study comparing the inter-observer reliability of these two approaches using the ratings of six clinicians on 12 patients. Systematic bias between observers was noted with both methods, but inter-observer agreement, as-assessed by the intraclass correlation coefficient (ICC), was higher with the score method. The manikin method resulted in a greater degree of disagreement between the observers, as well as a higher amount of random error, reflecting the difficulty of defining the bounds of abnormal skin. Despite the presence of bias, the score method is the preferred method for assessing the level of skin involvement. PMID- 1628169 TI - Phthalylsulphathiazole in rheumatoid arthritis. AB - Sixteen patients with active rheumatoid arthritis were treated with phthalylsulphathiazole (4 g/day) over a period of 24 weeks. Although there was some statistically significant improvement in plasma viscosity, IgM, pain score, morning stiffness and summated change score, this was either intermittent or not maintained. Five patients withdrew from the trial before completion, four (25%) with non-serious adverse reactions and one patient from lack of efficacy; only one patient elected to remain on the drug beyond the 24-week period. Low free and total sulphathiazole serum concentrations were found, confirming that most of the drug remained within the gut. This investigation suggests, certainly at the dose used, that phthalylsulphathiazole does not have the properties of a second-line agent. Higher doses of the drug will not be ethically feasible. PMID- 1628171 TI - Rheumatologists and their patients who seek alternative care: an agreement to disagree. AB - Alternative treatment, such as homoeopathy, acupuncture and spiritual healing, are popular among patients with rheumatic diseases. Rheumatologists are therefore likely to be confronted with patients who make use of less orthodox health care. Patients' and rheumatologists' views on the subject and on the rheumatologists' role, however, have not yet been assessed. A questionnaire on alternative medicine was sent to all 101 practising Dutch rheumatologists (response rate: 70%). After the results had been analysed 17 rheumatologists, seven rejecting alternative medicine and ten accepting it, handed out a questionnaire to a sample of their patients: 1466 patient questionnaires were distributed (response rate: 80%). Of the respondents 43% had visited an alternative practitioner at least once for their rheumatism and 26% in the year before the survey was held. Hand healers, homoeopaths and acupuncturists were most often visited. Rheumatologists, on their part, were not too enthusiastic about these visits. Only patients' visits to spa treatment centres were welcomed by a majority of them; visits of their patients to manipulative therapists, acupuncturists and homoeopaths were judged positively by a large minority, whereas other therapies were strongly disapproved. Nevertheless, most patients informed their rheumatologist about their visiting an alternative practitioner. A surprisingly low percentage of these patients noticed that the rheumatologist did not sympathize with it. Although many patients paid a visit to an alternative practitioner because regular care did not really help them, their satisfaction with the alternative treatment turned out to be less than their satisfaction with the rheumatologists' help.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628170 TI - Ophthalmological examinations of patients with primary Sjogren's syndrome selected from a rheumatological practice. AB - Ophthalmological examination of patients with primary Sjogren's syndrome (SS) (n = 44) taken randomly from a rheumatological practice revealed that in this population group the eyes were frequently but not seriously involved (n = 42). Primary SS patients (n = 44) could not be separated from patients suspected of primary SS, in whom the diagnosis had been excluded (n = 21) on the basis of ocular examination, but they were clearly distinguishable from healthy controls (n = 26). The diagnostic value of the tests currently in use to establish the diagnosis keratoconjunctivitis sicca in primary SS such as Schirmer's, tear film break up time and rose bengal staining tests appeared to be limited. These results demonstrate the heterogeneity of the syndrome, the influence of patient selection on patient characteristics in different primary SS populations and the limited value of using the present classification criteria for the diagnosis primary SS in individual patients. PMID- 1628172 TI - Osteoarticular tuberculosis of the symphysis pubis presenting as a hypogastric cystic mass in a woman with primary Sjogren's syndrome. AB - A 79-year-old woman with primary Sjogren's syndrome and immune thrombocytopenia presented with a hypogastric cystic mass. Twenty-three months previously she received a 7-month course of prednisone at moderate doses to control the thrombocytopenia. A computed tomography showed a cystic mass, destruction of the left pubis with involvement of the symphysis and erosion of the right pubis. The cystic mass was surgically removed. Epithelioid granulomata were found on pathological examination and Mycobacterium tuberculosis was grown in Lowenstein medium. This is the first reported case of osteoarticular tuberculosis with such a presentation and only the second localized to the pubis. PMID- 1628173 TI - Synovial cysts and sarcoid synovitis. AB - The case of a practice nurse who presented with painless cystic swellings in the popliteal and antecubital fossae and lymphoedema of the legs is reported. Biopsies of synovium, a breast lump, axillary lymph nodes and of the Kveim site demonstrated sarcoidosis. Prior to biopsy diagnosis was not obvious. Synovial cysts are a very rare manifestation of sarcoid joint disease and this case illustrates the importance of biopsy in establishing the diagnosis. PMID- 1628174 TI - Daily and alternate-day azathioprine treatment in rheumatoid arthritis: a twelve week controlled clinical trial. PMID- 1628175 TI - Fumaric acid therapy for psoriatic arthritis. A randomized, double-blind, placebo controlled study. PMID- 1628176 TI - Increasing patient throughput in magnetic resonance imaging: a practical approach. Oxford MRI Group. AB - A major factor governing the throughput of patients in a magnetic resonance imaging (MRI) service is the number and length of sequences employed. This study investigated the feasibility of prospectively selecting patients for whom a pre planned examination of the brain, spine or knee could be applied with a high chance of success. The implications on throughput of using these pre-planned examinations were determined. 173 patients were studied. A successful outcome was defined as an examination in which a diagnosis could be made with 100% confidence and without the need for further sequences. Examinations of the brain (n = 113), knee (n = 23) and lumbar spine (for disc degeneration, n = 14) were performed with success rates of 96%, 87% and 64%, respectively. Examinations of the lumbar spine (for radicular symptoms, n = 20) and cervical spine (n = 3) were performed with success rates of 85% and 66%, respectively. The examinations of the brain, knee and lumbar spine (for disc degeneration) were completed within the target time of 20 min in 92%, 95% and 69% of cases, respectively. Examinations of the lumbar spine (for radicular symptoms) and cervical spine were completed within 30 min in 75% and 33% of cases, respectively. Analysis of our results suggests that success rates could be improved by minor changes in sequence design. Carefully selected patients can be successfully examined in short examination times. Instituting these practices would increase the efficiency of MR machine time and improve patient throughput by 80-125%. This would have a marked effect on the length of waiting lists, and would increase the general availability of MRI. PMID- 1628177 TI - Radiological features during and following treatment of spinal tuberculosis. AB - A retrospective study was performed in order to document the sequence and time scale of radiological changes occurring during the healing of spinal tuberculosis. 28 episodes occurred in 26 patients, of whom only two were Caucasian. All demonstrated good response to conventional chemotherapy. Soft tissue masses increased in size for up to 1.5 months and took about 12 months to resolve. Bone destruction was seen in all cases and progressed in 70% of patients, whilst on treatment. There was loss of vertebral body height in 79%, which progressed for up to 14 months; any recovery of height was a very late feature. Sclerosis was seen at presentation in 52% and developed in most of the remaining patients within 5 months of instigating treatment. It progressed for up to 14 months and took, on average, 31 months to return to normal. Reduction in disc height was commonly seen and the vertebrae fused in three-quarters of those affected, the time of onset of fusion being very variable. To manage patients with spinal tuberculosis, an appreciation of the variability of radiological changes that can occur during treatment is necessary. PMID- 1628178 TI - The musculoskeletal manifestations of epidermolysis bullosa: an analysis of 19 cases with a review of the literature. AB - Epidermolysis bullosa encompasses a group of rare disorders characterized by marked skin fragility and blister formation. In patients with dystrophic epidermolysis bullosa, skeletal and soft-tissue abnormalities are an important feature. An analysis of the musculoskeletal manifestations in 19 patients is presented. In the hands and feet, features included generalized osteoporosis, wedge-shaped thinning and hooking of distal phalanges, overconstricted bones, acro-osteolysis, flexion contractures, metatarsal and metacarpal subluxation, distal trophic changes, webbing of digits, encasement of the whole extremity in a pouch of skin, soft-tissue calcification and retarded skeletal maturity. Previously undescribed findings in the hands and feet are bony ankylosis of the proximal interphalangeal joints, resorption of the metatarsal and metacarpal heads, shortened metatarsal bones, carpal and tarsal fusion and destruction, and cystic changes of the distal radius and ulna. In the remainder of the skeleton, hip dysplasia with premature osteoarthritis, knee joint bony ankylosis and thoracic and thoraco-lumbar scoliosis are other undescribed findings. PMID- 1628179 TI - Intramuscular myxoma: magnetic resonance features. AB - Magnetic resonance imaging (MRI) was performed in six cases of intramuscular myxoma of the extremities and revealed the following characteristics. All tumours were confined to muscle and had a sharply defined border. All had a signal intensity lower than skeletal muscles on T1-weighted images and brighter than fat on T2-weighted images. The signals were homogeneous on both T1- and T2-weighted images. This study did not include contrast enhancement. The diagnosis was confirmed by an open biopsy. All tumours were resected with no recurrence. Diagnosis based on these MRI characteristics was incorrect in two cases of intramuscular ganglia and in a case of intramuscular cysticercus cellulose. MRI features of intramuscular myxoma are typical in the majority of cases. Benign intramuscular lesions that contain mainly fluid can mimic intramuscular myxomas. PMID- 1628180 TI - Scintigraphic abnormalities in patients with painful hip replacements treated conservatively. AB - A retrospective review of the scintigraphic appearances of 98 painful hip replacements was made. 16 patients (16%) underwent revision surgery whereas in the remaining 82 hips (84%), symptoms settled with conservative management. 73 of these (89%) had at least one area of increased activity on delayed diphosphonate scintigraphy with 27% having increased activity in three or more areas around the femoral component. Hips with increased activity at the lesser trochanter and tip were less likely to undergo spontaneous resolution of symptoms. Uncemented prostheses were more likely to have multiple areas of increased activity. Abnormalities in dynamic bone scintigraphy and gallium studies were also seen in patients whose symptoms resolved without surgery. Whereas a normal bone scintigram indicates that loosening or infection is most unlikely, the presence of increased activity does not necessarily indicate a need for revision surgery, even when multiple areas are present. A period of conservative management should be considered before operative intervention is undertaken. PMID- 1628181 TI - Magnetic resonance imaging of pulsatile cerebrospinal fluid flow by spatial modulation of magnetization. AB - Various orders of binomial spatial modulation of magnetization sequences up to (1 4 6 4 1) have been tested to find the optimum sequence for clinical application. Stripe width, stripe sharpness and the tolerance of the sequences to radiofrequency non-linearity have been investigated. The (1 3 3 1) sequence was found to be a good compromise between competing design criteria, and its application to viewing pulsatile cerebrospinal fluid motion is described. PMID- 1628182 TI - The value of magnetic resonance relaxation time in staging ovarian endometrial cysts. AB - We evaluated the use of magnetic resonance imaging (MRI) in the pre-operative staging of 15 endometrial cysts. The effect of the iron content on the T1 and T2 relaxation times was assessed in confirmed endometrial cysts employing a 0.15 T MR system and a 200 MHz spectrometer. There was a positive linear correlation (r = 0.93) between the T1 values of the lesions obtained using the MR system (T1) and those of the resected cyst contents obtained using the spectrometer (sp-T1). A similar relationship was found between T2 and sp-T2 (r = 0.87). There was a negative linear relationship between the T1 value and the cyst iron content (r = 0.81), but there was no relationship between the T2 value and the iron content. T1 was 412 +/- 91 ms for Stage II cysts (n = 3), 356 +/- 126 ms for Stage III cysts (n = 3) and 208 +/- 30 ms for Stage IV cysts (n = 9). The T1 value for Stage IV cysts was significantly shorter than that for Stages II and III cysts (p less than 0.05). Thus, the T1 value was useful in distinguishing fresh from old endometrial cysts, suggesting that the MRI T1 relaxation time might be useful for staging ovarian endometrial cysts before surgery. PMID- 1628183 TI - Audit in action: significant reduction of double-contrast barium enema screening time with no loss of examination quality. AB - The double-contrast barium enema is an examination of high radiation exposure to the patient. As part of a departmental audit, our own fluoroscopic screening times were being recorded. A study was undertaken to see if a determined effort could reduce the screening time without having a detrimental effect on the quality of the examinations. Methods of screening time reduction were identified and then implemented by two radiologists. In the period before the study the average screening time for radiologists A and B was 2.6 min and 3.2 min, respectively (over 56 examinations). After implementation of the changes, the average screening time for both was 0.9 min (over 50 examinations). This is a statistically significant reduction (p less than 0.01). The examinations were assessed independently by a gastroradiologist. No difference in the quality of the examinations was identified. We conclude that a significant reduction of screening time for the double-contrast barium enema can be achieved without loss of examination quality. PMID- 1628184 TI - The application of microdosimetry in clinical bone densitometry using a dual photon absorptiometer. AB - Experimental microdosimetric methods have been used to determine absorbed dose values for a scanning dual-photon absorptiometer. Absorbed doses within the scanned field have been obtained for three different scanning speeds. For the normal speed setting used clinically, measurements have also been carried out in a water-filled phantom in order to estimate typical patient entrance, exit and midline doses. The results agree well with values obtained using thermoluminescence dosimetry and support the claims of the manufacturers with regard to upper limits placed on patient dose levels. The microdosimetric method enables changes in radiation quality to be followed and comparisons to be made with other low-energy photon fields used in medical diagnosis. PMID- 1628185 TI - A preliminary investigation of the imaging performance of photostimulable phosphor computed radiography using a new design of mammographic quality control test object. AB - Leeds Test Object TOR[MAM] has been designed to supplement the current FAXIL mammography test object TOR[MAX]. It contains a range of details that have a more natural radiographic appearance and has been designed as a test that more closely approximates the image quality achieved in clinical mammography. Physical aspects of the design and implementation of TOR[MAM] are presented. The TOR[MAM] has been used in a preliminary physical evaluation of the comparative image qualities produced by conventional (screen-film) and photostimulable phosphor computed mammography and the results are discussed. TOR[MAX] results are also presented. The influence of digital image processing (enhancement) on the image quality of computed mammograms is also considered. The results presented indicate the sensitivity of TOR[MAM]. PMID- 1628186 TI - A manual afterloading technique for the treatment of patients with bronchial carcinoma using iridium-192 wire. PMID- 1628187 TI - Technique for steel coil embolization of biopsy track for use with the "Biopty" needle. PMID- 1628188 TI - Splenic cyst: demonstration of the relationship between subcapsular haematoma and false cyst by imaging. PMID- 1628189 TI - Juxtaglomerular cell tumour of the kidney as cause of hypertension: a case report. PMID- 1628190 TI - Contrast extravasation from a Pulse-Tec graft: a complication of high-dose recombinant tissue-type plasminogen activator therapy. PMID- 1628191 TI - Pancreatic metastasis from renal cell carcinoma. PMID- 1628192 TI - Mistaken hilar mass. PMID- 1628193 TI - Results from the HAD psychometric questionnaire in 54 breast cancer patients treated with breast conservation. PMID- 1628194 TI - Measurement of tissue perfusion by dynamic computed tomography. PMID- 1628195 TI - Mesenteric lymphadenopathy in idiopathic retroperitoneal fibrosis. PMID- 1628196 TI - Now you see it ... now you don't. PMID- 1628197 TI - Neurology of otolith function. Peripheral and central disorders. AB - The otolith organs detect gravitoinertial forces acting on the head providing signals to the brain which are essential for spatial orientation, sensing motion and organizing motor behaviour. Although the pathophysiology of otolithic dysfunction is poorly understood, a disorder of otolith function, at a peripheral or central level, may be suspected when a patient describes symptoms of false sensations of linear motion or tilt or shows signs of specific derangements of ocular motor and postural, orienting and balancing responses. When disorientation is severe the patient may describe symptoms which sound bizarre, raising doubts over the organic basis of the disease. Our recognition of an otolithic disorder and understanding otolithic involvement in a wider neurological context may be guided by knowledge of otolith physiology and of the characteristics of the few proven otolithic syndromes. PMID- 1628198 TI - Visuospatial attention in dementia of the Alzheimer type. AB - Cue-directed shifts of spatial attention were examined for a letter discrimination task in 15 patients with mild to moderate dementia of the Alzheimer type (DAT) and 15 healthy, age-matched controls. Spatial cues were valid, invalid or neutral in indicating probable target location and were presented either centrally at fixation or peripherally 6.7 degrees to the left or right of fixation. Stimulus-onset asynchrony (SOA) between cue and target was varied between 200 ms and 2000 ms. Reaction time (RT) benefits conferred by valid cues did not differ between the DAT group and the controls. However, RT costs incurred by invalid cues were significantly greater in the DAT group than in the control group. Group differences in RT costs plus benefits occurred at short SOAs (less than 500 ms) for peripheral cues and at long SOAs (greater than 500 ms) for central cues. Reaction time costs plus benefits were correlated with right-left asymmetry in resting levels of cerebral glucose metabolism in the superior parietal lobe for DAT patients but not for controls. The results indicate that focusing of attention to spatial location is intact in early DAT, whereas the disengagement of visuospatial attention is impaired. Automatic attention shifts elicited by peripheral cues reveal abnormalities earlier than attention shifts initiated 'effortfully' by central cues. Intact focusing and impaired disengagement of visuospatial attention may be linked to dysfunction in early DAT of cortico-cortical networks linking the posterior parietal and frontal lobes. PMID- 1628199 TI - White matter lesions on magnetic resonance imaging in clinically diagnosed Alzheimer's disease. Evidence for heterogeneity. AB - In a prospective magnetic resonance imaging (MRI) study we evaluated the prevalence and severity of white matter changes in 29 patients with Alzheimer's Disease (AD) and 24 age-matched healthy elderly, all without cerebrovascular risk factors. The AD patients were divided into two groups according to age at onset of symptoms, one with presenile onset AD (n = 13) and one with senile onset AD (n = 16), who were matched for dementia severity. Signal hyperintensities were rated using a semiquantitative scoring method, separately in the periventricular region (PVH) and in the lobar white matter (WMH), as well as in the basal ganglia (BGH) and in the infratentorial region (ITFH). Cortical atrophy as a parameter of grey matter involvement was rated on a 0 (absent) to 3 (severe) scale. We found PVH, WMH and BGH scores to be significantly higher in senile onset AD patients than in age-matched controls. By means of multiple linear logistic regression we found that PVH, WMH and BGH scores were significantly dependent on the diagnosis of senile onset AD, while the PVH score also showed a significant age dependency. Cortical atrophy did not differ significantly between presenile onset AD and senile onset AD patients. These results indicate that presenile onset AD and senile onset AD patients differ with respect to white matter involvement, but not with respect to grey matter involvement on MRI. Since cerebrovascular risk factors were excluded these findings may indicate that senile onset AD patients display more small vessel involvement (arteriolosclerosis) than presenile onset AD patients, suggesting additional (microvascular) factors for the dementia syndrome in senile onset AD. Our data lend support to the growing body of evidence that AD is heterogeneous, consisting of at least two types. Based on our findings two forms can be distinguished: (i) a 'pure' form of the disease, usually with early disease onset, and no more white matter changes than normal for age; (ii) a 'mixed' form, usually with disease onset later in life, and showing more white matter changes on MRI than normal for age. PMID- 1628200 TI - Pure amnestic seizures in temporal lobe epilepsy. Definition, clinical symptomatology and functional anatomical considerations. AB - Pure amnestic seizures (PAS) sometimes occur in patients with temporal lobe epilepsy. They never represent the only type of seizures in these patients. Pure amnestic seizures are defined as seizures during which the only clinical manifestation is the patients' inability to retain in memory what occurs during the seizure coupled with the preservation of other cognitive functions and the ability to interact normally with their physical and social environment. It is postulated that PAS result from selective ictal inactivation of mesial temporal (MT) structures without isocortical involvement. This occurs most often in patients with neuropsychological and electroencephalographic (EEG) evidence of bilateral dysfunction of MT structures (six out of eight patients in this study). In the few patients without such evidence as well as in some with bilateral MT dysfunction, PAS may result from seizure discharge limited to the MT structures of both temporal lobes. In the light of current anatomical knowledge, contralateral spread of seizure discharge from the MT structures of one side to those of the other through the dorsal hippocampal commissure is the only likely explanation for this situation. One observation with depth electrode stimulation of MT structures supports this view. In patients with evidence for bilateral MT dysfunction, a unilateral seizure may presumably suffice to induce a PAS, the contralateral MT structures being unable to ensure normal memory function. In most instances PAS can be distinguished from episodes of transient global amnesia on clinical grounds. PMID- 1628201 TI - Epileptic seizures in an Andean region of Ecuador. Incidence and prevalence and regional variation. AB - A large-scale neuro-epidemiological study was carried out in a population of 72,121 inhabitants of a region of Northern Ecuadorian Andean Sierra, to identify prevalence and incidence rates of epileptic seizures and to identify demographic and geographic variations in these rates. Calculations were made using three datasets. First, rates were calculated from all cases identified in the field (raw dataset); secondly, lower rates were calculated based on a further diagnostic and reclassification procedure (minimum estimated dataset); thirdly, higher rates were derived by calculating false negative rates from the screening procedures, and adding these to the cases actually identified (maximum estimated dataset). Lifetime point-prevalence rates between 12.2/1000 and 19.5/1000 were recorded (minimum and maximum estimated rates), and the prevalence of active epileptic seizures was between 6.7/1000 and 8.0/1000 (minimum estimated and raw datasets). Incidence rate ranging between 122/100,000/year and 190/100,000/year were found (minimum, estimated and raw datasets). A marked difference in prevalence rates was found in two subregions of the survey area, and also in urban and rural areas. The reasons for these differences were not identified. PMID- 1628202 TI - Validation of a screening questionnaire for the detection of epileptic seizures in epidemiological studies. AB - A large-scale clinico-epidemiological study of epileptic seizures has been carried out in a highland area in northern Ecuador, South America. This paper describes the design and the two-staged validation procedures undertaken to authenticate the screening questionnaire, which was used to detect epileptic seizures in the community during this project. An initial questionnaire consisting of 20 questions was devised and then validated in a group of healthy subjects and a group of patients with known epileptic seizures. This questionnaire was found to have a sensitivity of 100% and a specificity of 50.8%. A cluster analysis of the responses rates was undertaken and a set of nine questions which presented a specificity of 92% and sensitivity of 98% were chosen to be used during the survey. The validation of this nine-question instrument was then undertaken by direct application to a general population of 72,121 persons. Positive, negative, false positive and false negative rates were derived. The screening instrument was found to have a sensitivity of 79.3%, a specificity of 92.9%, a positive predictive value of 18.3%, a negative predictive value of 99.6% and a Youden's index of 0.79. The methodology of the study and the instruments developed are recommended for future neuro-epidemiological work in epilepsy. The problems of validation are discussed, and previous epidemiological studies of epilepsy reviewed with special emphasis on the handling of questions of validation. PMID- 1628203 TI - Brain energy metabolism in bilateral paramedian thalamic infarcts. A positron emission tomography study. AB - Positron emission tomography (PET) studies of the cerebral metabolic rate of oxygen (CMRO2) were performed in seven consecutive patients with bilateral paramedian thalamic infarcts (BPTI), selected on neuroradiological and clinical criteria. The latter consisted of sudden onset of coma or confusion followed by a persistent amnesia of varying severity, with or without language impairment and frontal lobe signs. There was a highly significant decrease of CMRO2 for the whole cortex as well as for all the regions analysed: medial-frontal, latero frontal, temporal, sensorimotor and posterior associative cortex. The mean regional metabolic ratios (region/whole cortex CMRO2) were not significantly different from controls, indicating an essentially uniform effect in the cortex, except the sensorimotor ratio which was significantly increased. Diffuse cortical hypometabolism most likely reflects thalamo-cortical deafferentation secondary to damage to the 'non-specific' thalamic nuclei, while sparing of the latero-ventral thalamus presumably explains the relative preservation of the sensorimotor cortex metabolism. Although no clear-cut individual relationship was found between magnitude of cortical hypometabolism and the severity and pattern of neuropsychological impairment, the data suggest that the former underlies and/or reflects the latter. Further studies with higher resolution PET devices might shed more light on the relationships between distinct cognitive patterns and specific topography of cortical hypometabolism in BPTI patients. PMID- 1628204 TI - A 2-deoxyglucose study of the effects of dopamine agonists on the parkinsonian primate brain. Implications for the neural mechanisms that mediate dopamine agonist-induced dyskinesia. AB - The neural mechanisms that underlie both the anti-parkinsonian effects of dopamine agonists and dopamine agonist-induced dyskinesia were studied in parkinsonian primates, using the regional brain uptake of [3H]2-deoxyglucose (2 DG). Parkinsonian symptoms were induced in monkeys by the administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Some of the animals received chronic dopamine replacement therapy for at least 3 mths, which resulted in the appearance of peak-dose dyskinesia. The remaining animals spent an equivalent period of time relatively unexposed to dopaminergic agents, receiving only therapeutic doses, and at no time showed any signs of dopamine agonist-induced dyskinesia. The 2-DG metabolic mapping technique was applied to all of these animals shortly following the administration of a dose of dopamine agonist which was sufficient to alleviate their parkinsonian symptoms and to induce dyskinesia in those prone to this complication. The 2-DG uptake technique permits the autoradiographic measurement of local cerebral glucose uptake which was used as an index of regional synaptic activity. The resultant autoradiographs were compared with those from a previous study which examined 2-DG uptake in parkinsonian and normal brains from animals which had not received dopamine agonists prior to the terminal 2-DG uptake procedure. The pattern of 2-DG uptake in the animals which received a dopamine agonist prior to the terminal procedure was strikingly different to both of the other groups. The most affected structure was the subthalamic nucleus which showed a dramatic increase in 2-DG uptake in animals exposed to dopamine agonist immediately prior to the terminal procedure, especially in the ventral tip of the nucleus. The medial pallidal segment also showed relatively greater levels of 2-DG uptake in the dopamine agonist group compared with the untreated parkinsonian state whereas, in contrast, the lateral pallidal segment showed decreased levels of 2-DG uptake. The parkinsonian animals which had been sacrificed after receiving a dopamine agonist were split into three groups on the basis of their response to the agonist. The first group had their parkinsonism reversed and appeared clinically normal. The remaining animals had their parkinsonism reversed by the dopamine agonist but showed dyskinesia at peak dose. These animals were allotted to two further groups depending on whether their dyskinesia was of a choreic or dystonic nature.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1628205 TI - Motor sequencing with left hemisphere damage. Are some cognitive deficits specific to limb apraxia? AB - Sixteen left-hemisphere stroke patients, who were apraxic or nonapraxic, and 17 control subjects performed sequences of hand postures that varied in the number of different postures (repetitive and heterogeneous) and sequence length (one to five). Performance of the left hand (ipsilateral to stroke) was compared with a control group using the left hand. All stroke patients had slower reaction times and were slower to execute single hand postures, but the apraxic group was not slower than the nonapraxic group. Both the apraxic and the nonapraxic groups had similar problems scheduling or timing motor programs for both sequence types such that inter-response times were more affected by sequence length than the control group. However, only the apraxic group showed abnormalities in preprogramming heterogeneous sequences. The apraxic group also made more errors and had longer movement times (MTs) than for the other groups, but only for heterogeneous sequences containing more than three hand postures. The nonapraxic group did not show slower MTs or greater errors, regardless of the type or the length of sequences. These results suggested deficits in encoding, generating single movements and in scheduling or timing a series of actions which generally attributable to left hemisphere damage. However, abnormalities in temporal organization processes prior to and during movement were specific to apraxia. The dissociation between the two stroke groups on some but not all aspects of sequencing has implications for different cognitive mechanisms supporting motor sequencing. PMID- 1628206 TI - Performance of repetitive wrist movements in Parkinson's disease. AB - The timing of repetitive alternating 80 degrees flexion-extension movements of the right wrist was studied in 42 patients with Parkinson's disease, tested while not receiving dompaminergic medication and 20 age- and sex-matched controls. Five rates of movement (0.5 Hz, 1 Hz, 1.5 Hz, 2 Hz, 2.5 Hz) were examined. The interval between two successive flexion movements, as measured from the electromyography (EMG) records was taken as the unit of analysis or inter response interval (IRI). At 0.5 Hz, 1 Hz and 1.5 Hz there were no differences between groups in mean IRIs. At higher rates of movement (2 Hz and 2.5 Hz), however, the controls were significantly more accurate in timing of repetitive movements than the patients. At all five frequencies, the patients with moderate or severe Parkinson's disease were less accurate in timing of repetitive movements than those with mild disease, although the differences were not significant. In nine patients tested in the 'on' and 'off' medication states, administration of 250 mg of levodopa/carbidopa resulted in significantly more accurate timing of repetitive movements. Wing and Kristofferson's (1973b) two process model of repetitive movements was applied to the IRI data. At various rates of movement, the primary prediction of the model that lag 1 autocorrelations should be in the 0 to -0.5 range was violated in 40-70% of the patient and controls. For those subjects who had lag 1 autocorrelations in the expected range, IRI variability was to break down into a timekeeper and a motor delay variance. At all frequencies, the patients had significantly higher variance for IRI, timekeeper and motor delay than the controls. Although not significant, more severe Parkinson's disease was associated with greater IRI, timekeeper and motor delay variance, while administration of levodopa resulted in reduction of the three types of variance. The validity of the Wing and Kristofferson model for the analysis of this type of movement is discussed. PMID- 1628207 TI - Quantitative somatosensory thermotest. A key method for functional evaluation of small calibre afferent channels. AB - The quantitative somatosensory thermotest (QST) assesses the function of afferent channels concerned with sensory submodalities served by small calibre fibres. Measured ramps of ascending or descending temperature are applied to the skin through a Peltier contact thermode, and detection thresholds are recorded as the subject signals the onset of a particular sensation. The present study describes underlying principles, methodological aspects and normal reference values for the QST. In patients, measurement of thresholds for cold sensation, warm sensation, cold-induced pain and heat-induced pain, applied to 465 individuals, yielded 13 abnormal patterns segregated into three main groups: (i) thermal (cold or warm) hypoaesthesia; (ii) thermal hyperalgesia (abnormally reduced threshold for cold and/or heat induced pain); (iii) thermal hypoaesthesia combined with thermal hyperalgesia. Critical analysis of these results yielded a number of observations of general relevance: (i) thermal specific (warm or cold) hypoaesthesia and thermal (heat or cold) hyperalgesia may occur in the absence of hypoaesthesia for tactile submodalities served by large calibre afferents; (ii) cold hypoaesthesia and warm hypoaesthesia may dissociate from each other; (iii) thermal pain hyperalgesias may occur in the absence of hypoaesthesias for specific cold or warm sensations; (iv) cold hyperalgesia and heat hyperalgesia may dissociate from each other. Thus, a negative routine sensory examination and unimpaired sensory nerve action potentials do not exclude possible somatosensory dysfunction. Furthermore, while most methods of sensory testing only document normality or deficit, the QST permits additional documentation of hyperalgesia, a positive sensory phenomenon that implies unusual pathophysiologies such as sensitization of receptors, central hyperexcitability, disinhibition or, possibly, ectopic nerve impulse discharge. This psychophysical test does not specify the level within afferent channels, between skin and brainmind, where the abnormality resides. It is recommended that the QST for all four thermal specific and thermal pain functions be incorporated in routine neurological assessment. PMID- 1628208 TI - Determination of the segmental sensory and motor innervation of the lumbosacral spinal nerves. An electrophysiological study. AB - The knowledge of the segmental innervation of the skin and muscles of the lower limb in man is inadequate. For this reason, sensory and motor segmental innervation of the lower extremities was examined by electrophysiological methods in 27 normal subjects, one patient with possible L5 radiculopathy and one with possible lumbosacral plexus affection. Needle electrodes were placed at root levels from L3 to S2 using bony landmarks. The electrode was then placed close to the spinal nerve as indicated by a low (less than or equal to 1 mA) threshold necessary to stimulate motor fibres. The position was controlled by X-ray in 10 subjects. Sensory innervation was determined by recording the sensory action potential evoked by stimulating the saphenous nerve at the medial epicondyle (mainly L3 and L4) and at the medial malleolus (mainly L4 and in some L3), the medial plantar nerve at the first plantar interstice (mainly S1, some L5 and S2), the deep peroneal nerve at the first dorsal interstice (mainly L5, some S1), the sural nerve at the dorsolateral aspect of the foot (mainly S1, some L5 and S2) and at the lateral malleolus (mainly S1, some L5 and S2), and the superficial peroneal nerve at the superior extensor retinaculum (mainly L5, S1). The motor innervation was determined by stimulating the spinal nerves supramaximally and recording the evoked responses from the medial and lateral vastus (mainly L3, L4), the anterior tibial (mainly L5), the peroneus longus (L5, S1), the extensor digitorum brevis (mainly S1), the gastrocnemius (mainly S1), the abductor hallucis (mainly S2) and the biceps femoris (mainly L5, S1). Sensory and motor conduction velocity measurements along the leg and across the lumbosacral plexus indicated that there was no difference in a disto-proximal direction, except for a 10% reduction along the most distal part of the sural nerve which, however, might be explained by utilization time. There was therefore no evidence of gradual tapering of nerve fibres in a distal direction. The proximal motor conduction velocity to the most distally placed muscle (abductor hallucis) was about 20% lower than to the proximally placed muscles (gastrocnemius and biceps femoris) suggesting a general difference in fibre calibre. PMID- 1628209 TI - Distal motor axonopathy and central nervous system myelin vacuolation caused by cycloleucine, an inhibitor of methionine adenosyltransferase. AB - Cycloleucine (CL), an inhibitor of methionine adenosyltransferase, has previously been used to produce an experimental model of subacute combined degeneration of the spinal cord. A re-investigation of its effects on the morphology of the nervous system and on brain concentrations of methionine and S-adenosylmethionine (SAM) was undertaken. Cycloleucine was administered as a single dose intraperitoneally (2 mg/g body weight) to young mice aged 21 d and adults aged 6 or 10 wks. The 21-day-old mice showed clinical evidence of toxicity within 24 h and thereafter developed progressive muscle weakness and ataxia. Animals did not survive longer than 1 wk. Light and electron microscopic examination of the central and peripheral nervous systems showed that intramyelinic vacuolation developed in the white matter of brain and cord within 12 h. The intramyelinic vacuolation in the white matter of brain and cord became more severe with longer survival, vacuoles coalescing and secondary axonal degeneration becoming evident. There was no myelin vacuolation in peripheral nerves. Axonal lesions occurred in the distal parts of motor nerves within 12-24 h resulting in degeneration of intramuscular nerve fibres and terminals. Later there was evidence of axonal degeneration in tibial and sciatic nerves. Many dorsal root ganglion cells became vacuolated or necrotic and numerous degenerated fibres were noted in the white matter of the spinal cord, particularly in the gracile funiculus. The optic nerves were not affected at any stage. In adult mice the pathology consisted of distal motor axonal degeneration which developed at 1-2 d. Little or no intramyelinic vacuolation in white matter was noted. Brain concentrations of SAM were reduced and levels of methionine became greatly elevated. The morphological effects of CL are considered to be the result of SAM deficiency impairing transmethylation processes known to be important in the formation and stabilization of myelin through the methylation of myelin basic protein. The immature developing central nervous system is much more vulnerable than the fully myelinated adult brain and spinal cord. The distal, predominantly motor axonopathy is a new observation and may be a reflection of the importance of transmethylation processes in the maintenance of axonal terminal membranes and the mechanisms of release of acetylcholine at the neuromuscular junction. PMID- 1628210 TI - Correlation between behavioral sensitization to cocaine and G protein ADP ribosylation in the ventral tegmental area. AB - The ventral tegmental area is a site of action by psychostimulants in the production of behavioral sensitization. Recently, G proteins of the ventral tegmental area have been implicated in behavioral sensitization to cocaine. To further investigate the specific role of G proteins, rats were treated with either 15 or 30 mg/kg, i.p., of cocaine (x 5 days), and at 1, 6 or 24 h after the last injection in vitro pertussis toxin catalyzed adenosine diphosphate (ADP) ribosylation was used to measure the G proteins in the ventral tegmental area, nucleus accumbens, prefrontal cortex, substantia nigra, and striatum. A significant decline in the ADP-ribosylation of G proteins, specific for the ventral tegmental area, was observed at 1 and/or 6 h but had returned to normal by 24 h. A significant negative correlation was found between the percent of G proteins ADP-ribosylated in the ventral tegmental area and the behavioral activity elicited in sensitized but not acute cocaine-treated animals at 1 h after injection. These data suggest that the G proteins ADP-ribosylated by pertussis toxin may be involved in the sensitized motor response produced by repeated cocaine administration in rats. PMID- 1628211 TI - Neuropeptide-induced cytosolic Ca2+ transients and phosphatidylinositol turnover in cultured human retinal pigment epithelial cells. AB - Neuropeptide-induced mobilization of cytosolic free Ca2+ concentration ([Ca2+]i) and phosphatidylinositol (PI) turnover in cultured human retinal pigment epithelial (RPE) cells were studied and their temporal relationship was compared. After RPE cells were loaded with fura-2/AM, [Ca2+]i was analyzed using a digital imaging microscopy system. Bombesin-related peptides which include bombesin, neuromedin B, and neuromedin C induced significant [Ca2+]i transients in RPE cells, whereas other neuropeptides, neuropeptide Y, vasoactive intestinal polypeptide (VIP), and substance P were not effective to produce [Ca2+]i transients. The percentage of reactive cells which showed positive [Ca2+]i transients induced by bombesin-related peptides was around 50%. Bombesin (1 microM) showed a peak concentration of 663 +/- 27.0 nM (mean +/- S.E.M., n = 61), neuromedin B (1 microM), 327 +/- 28.7 nM (mean +/- S.E.M., n = 38), and neuromedin C (1 microM), 357 +/- 22.7 nM (mean +/- S.E.M., n = 32). Ca2+ transients occurred within 30 s and lasted less than 5 min after the application of the neuropeptides. Chelation of the extracellular Ca2+ by EGTA significantly shortened the total time of [Ca2+]i transients induced by the above. The measurements of phosphoinositides in RPE cells revealed that neuropeptide-induced PI turnover was as quick as [Ca2+]i transients. Inositol biphosphate (IP2) and inositol triphosphate (IP3) in RPE cells showed transient increases at 15 s after the stimulation by bombesin-related peptides. These data show that changes in [Ca2+]i and PI turnover are directly linked and both are important in the signal transduction system of bombesin-related peptides in RPE cells. The data also suggest that bombesin-related peptides may play some possible roles in RPE cells. PMID- 1628212 TI - An oligodendrocyte precursor cell line from rat optic nerve. AB - We have established permanent cell lines from the optic nerve of the rat with a temperature sensitive immortalizing oncogene (Simian Virus 40 large T-antigen carrying both the tsA58 and U19 mutations). The oncogene was transduced into primary cultures via a replication deficient retrovirus, and infected cells were selected with the antibiotic G418. A clonal cell line (tsU19-5) displayed some properties of oligodendrocyte precursors: it proliferated, bound the monoclonal antibody A2B5 (which recognizes minor ganglioside species), and expressed the intermediate filament vimentin and the enzyme 2',3'-cyclic-nucleotide 3' phosphodiesterase (CNP) at 33 degrees C (the permissive temperature for the oncogene). At 39 degrees C (the non-permissive temperature), some cells had the potential to differentiate further, and expressed several oligodendrocyte specific components: galactocerebroside, myelin basic protein, proteolipid protein and CNP. These results suggest that conditional oncogenes can establish neural precursor cell lines which are still capable of differentiation in vitro. PMID- 1628213 TI - Changes in discharge rate of cat hamstring fusimotor neurones during fatiguing contractions of triceps surae muscles. AB - Changes in the discharge rate of fusimotor neurones to hamstring muscles during long-lasting, fatiguing, contractions of the triceps surae muscles were studied in decerebrate cats. Discharges of fusimotor neurones were recorded from the nerve filaments. Muscle contractions were elicited by electrical stimulation of the muscle nerves applied until the muscle tension fell to about 30% of its initial value. Early and late changes could be recognized in fusimotor discharge rate. The early changes, at the onset of muscle contraction, occurred in 9 out of 22 neurones and varied in both sign and duration among the cells. The late change, encountered in 16 fusimotor neurones, was an increase in discharge rate developing towards the end of the muscle contraction and outlasting it. When the contracting triceps muscle was made ischaemic the late increase in discharge rate developed earlier, as did the muscle tension fall and started to subside after the arterial clamp was removed. After severing the muscle nerves their stimulation provoked either no changes or a slight sustained decrease in fusimotor discharge rate. It is supposed that the late increase in discharge rate of fusimotor neurones to hamstring muscles appears due to reflex excitation by discharges in group III and IV afferent fibres from the triceps muscle provoked and/or enhanced by metabolic products liberated during its fatiguing contraction. The possibility is raised that the excitation is elicited primarily by the discharges from chemosensitive afferent fibres. Its functional role in muscle fatigue is discussed. PMID- 1628214 TI - A parametric analysis of the effects of cardiopulmonary vagal electrostimulation on the digastric reflex in cats. AB - The thoracic trunk and the cardiac branch of the vagus were stimulated electrically in chloralose-anesthetized cats. The experiments were conducted to determine the parameters of vagal afferent stimulation (VAS) capable of producing an inhibition of the digastric reflex (DGR), to assess the duration of this inhibition, and to test whether endogenous opioids mediate the inhibitory effects. In experiments using intermittent trains of pulses, the effects of pulse number (1, 2, 7 or 35 pulses), frequency (13, 66 or 333 Hz), intensity (0.1, 0.5, 1, 2, 3, 4 or 5 mA), and duration (1 or 3 ms) were evaluated. A 7 pulse train (3 mA) was sufficient to produce maximal inhibition (77 +/- 7%) of the tooth-pulp stimulation-evoked DGR regardless of the pulse duration or frequency. These effects were mediated by vagal afferents since stimulation of the central end produced as much inhibition as stimulation of the intact nerve. VAS also significantly reduced the DGR when elicited by tooth-pulp intensities at 1x -5x threshold. In experiments using 90 s of continuous VAS, 16 combinations of frequency and intensity yielded a threshold intensity for DGR inhibition between 0.1 and 0.5 mA and a threshold frequency at 2 Hz. Maximal DGR inhibition was produced at 5 Hz-0.5 mA by VAS. Reflex inhibition occurred within 10 s and outlasted VAS for longer than 60 s. Opiate-receptor blockade did not alter VAS inhibition of the DGR and, thus, opioids are not likely to mediate VAS-induced digastric inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628215 TI - Electrolytic lesions of the locus coeruleus or 6-hydroxydopamine lesions of the medial forebrain bundle protect against excitotoxic damage in rat hippocampus. AB - Unilateral lesioning of the rat locus coeruleus by an electric current (0.3 mA/10 s) reduces the ipsilateral hippocampal tissue content of dopamine (DA) and noradrenaline (NA) by 80% and 60% respectively, and protects against the excitotoxic action of bilateral kainate injections (1.1 nmol/microliters) in the hippocampus. On the ipsilateral side hippocampal CA1, CA2 and DG cells were protected; lesser protection of CA1 cells was seen on the contralateral side. The unilateral injection of 6-hydroxydopamine (8.8 micrograms/2 microliters/5 min) into the medial forebrain bundle abolishes the increase in extracellular NA concentration induced by kainate in the ipsilateral hippocampus without altering the low extracellular DA levels. This medial forebrain bundle lesion protects (on the ipsilateral side) against kainate toxicity (500 microM through the probe for 20 min) in the hippocampus (CA1, CA2 and DG cells). The noradrenergic innervation of the hippocampus apparently potentiates the excitotoxic effect of focal injection of kainate. PMID- 1628216 TI - Variations of monoamines and their metabolites in the human brain putamen. AB - The levels of the monoamines dopamine (DA), serotonin (5-HT) and norepinephrine (NE) and the monoaminergic metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were measured with HPLC-ECD in 42 samples from human brain putamen. The influence of gender and of age was investigated and correlations between the monoamines were established. The DAergic system shows a significant difference between males and females, with females having lower DA and higher DOPAC levels and a higher DOPAC/DA ratio than males. No gender-related differences of 5-HT and its metabolites were observed, nor of NE. Three different age groups (group 1: 0-9.9 years: group 2: 10-59.9 years; group 3: 60 years and older) were defined according to previous studies on ontogenesis and senescence in human brain. An increase in 5-HT levels, decrease in 5-HIAA levels and a decrease in the 5-HIAA/5-HT ratio were observed after the first decade of life. Changes in the DAergic system were seen in senescence, with decreasing DA levels and an increase in the HVA/DA ratio. DOPAC, HVA and the DOPAC/DA ratio are unaffected. NE is similar in all age groups. The analysis of the relation of the levels of the three monoamines proved a strong correlation between the DAergic and 5-HTergic systems. The nature of this relationship might have an impact on neuro-psychiatric disorders and brain function. PMID- 1628217 TI - Anemia up-regulates pontine A1 adenosine receptors in fetal sheep. AB - A rise in central adenosine concentrations most likely triggers the inhibitory effects of acute hypoxia on fetal breathing movements. During prolonged O2 deficiency, the incidence of fetal breathing increases over time, an adaptation which may involve down-regulation of adenosine receptors. Therefore, isovolemic anemia was induced in chronically catheterized fetal sheep to determine the effects of acute O2 deprivation on the affinity of brainstem A1 adenosine receptors. Compared to control values, the mean hemoglobin concentration in 4 fetuses was lowered by 54% (to 3.7 +/- 0.4 g/dl) for 1 h and in 3 fetuses by 58% (to 3.8 +/- 0.6 g/dl) for 4 h. Mean preductal arterial pH during anemia was significantly reduced to values as low as 7.123 +/- 0.090, but mean paO2 and paCO2 were not significantly affected. The average incidence of fetal breathing movements was decreased by 80% during the first hour and by 50% during the fourth hour of anemia. In 3 fetuses with normal hemoglobin levels, about 32 +/- 6.0% of the A1 adenosine receptors in the brainstem were in the high affinity state. After 1 h of anemia, the percentage of high affinity receptors in the pons (but not medulla or midbrain) had significantly increased to 47 +/- 2.9%, but after 4 h of anemia all 3 brainstem regions had A1 receptor affinity within the range of control values. It is concluded that acute anemia induces a short-lived up regulation of pontine A1 adenosine receptors, but anemia does not alter A1 receptor coupling in the midbrain where A1 receptors related to breathing inhibition may be located. PMID- 1628218 TI - The role of corticotropin-releasing factor and vasopressin in hypoglycemia induced proopiomelanocortin gene expression in the rat anterior pituitary gland. AB - In this study, we examined the effect of passive immunization of endogenous corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) on hypoglycemia-induced adrenocorticotropic hormone (ACTH) secretion and determined proopiomelanocortin messenger RNA (POMC mRNA) levels in the anterior pituitary as well as hypothalamic CRF mRNA levels in pentobarbital anesthetized rats. The response of plasma ACTH to hypoglycemia was partially inhibited by the administration of CRF-antiserum (CRF-As) or AVP-antiserum (AVP-As) alone, but was found to be completely abolished by the administration of CRF-As + AVP-As as compared to the response in normal rabbit serum-treated rats. The hypoglycemia induced POMC mRNA level in the anterior pituitary was completely inhibited by the administration of CRF-As alone and CRF-As + AVP-As, but was not inhibited by AVP As alone as compared to the response in normal rabbit serum-treated rats. The administration of CRF-As and/or AVP-As did not affect hypoglycemia-induced CRF mRNA levels in the hypothalamus. These results indicate that the synergistic effect of CRF and AVP is important for hypoglycemia-induced ACTH secretion, but CRF is essential and indispensable for hypoglycemia-induced POMC gene expression in the anterior pituitary (AP). PMID- 1628219 TI - Calbindin D-28k-immunoreactivity in rat muscle spindle; a light and electron microscopic study. AB - The localization of the vitamin D-dependent calcium-binding protein, calbindin D 28k (CaBP), was studied immunocytochemically in rat striated muscle. CaBP-like immunoreactivity was found in some of the intrafusal fibres in muscle spindles. The spindle capsule and the perineurial sheath of the nerve bundles were occasionally immunoreactive to CaBP. In electron microscope the labelling for CaBP was found diffusely in sarcoplasm, in Z-bands and inside the terminal cisternae of intrafusal muscle fibres. The present findings suggest that CaBP may have a role in maintaining the appropriate microenvironment in the intracapsular space of muscle spindle and that CaBP may be involved in the function of intrafusal muscle fibres. PMID- 1628220 TI - c-fos proto-oncogene changes in relation to REM sleep duration. AB - Auditory stimulation has been shown to increase REM sleep periods in cats and humans. This effect has been attributed to an elevation of the level of excitability in a variety of brain stem neuronal groups. Fos-like immunostaining (FLI) has been useful in constructing maps of post-synaptic neuronal activity with single cell resolution, and has been suggested to be tightly correlated with ongoing neuronal activity. This study used FLI to quantify neurons from structures expressing c-fos in brain stem areas in animals with normal REMs and compared them with those showing extended REM periods. The results basically indicated that brain stem areas which in other studies have been described as having REM-ON cells, showed an increase in FLI, while no FLI changes occurred in areas described as having REM-OFF cells. These results are discussed in terms of the possibility that REM maintenance is related to a widespread increase in brain stem excitability. PMID- 1628221 TI - Phosphatidylinositol-specific phospholipase C activity in the postmortem human brain: no alteration in Alzheimer's disease. AB - The activity of phospholipase C (PLC) which hydrolyzes exogenous phosphatidylinositol (PI), was investigated in samples prepared from postmortem normal human brains and Alzheimer disease brains. The enzyme activity did not change significantly after rat brains were left for 24 h at room temperature. The PI-specific PLC activity in the Alzheimer cytosolic and particulate fractions was not significantly different from that in the control fractions. The PI-specific PLC activity as a function of the free Ca2+ concentration was also similar between control and Alzheimer brains. These results suggest that the PI-specific PLC activity is not altered in Alzheimer's disease. PMID- 1628222 TI - Basic fibroblast growth factor binds to filamentous inclusions of neurodegenerative diseases. AB - The extracellular matrix protein heparin sulfate proteoglycans (HSPG) has been found in the neurofibrillary pathology of Alzheimer disease. This study was performed to determine if similar proteoglycans might be present in the fibrillary inclusions of other neurodegenerative diseases. Basic fibroblast growth factor (bFGF) binding to heparinase sensitive sites was used as an assay for HSPGs. We found that the inclusions of Pick and Parkinson diseases as well as progressive supranuclear palsy contained heparinase sensitive bFGF binding sites while the inclusions of diffuse Lewy body disease lacked bFGF binding sites. These findings indicate that HSPG's interactions and possible role in the formation of intraneuronal inclusions are not limited to Alzheimer disease. PMID- 1628223 TI - Influence of task dynamics on the organization of interlimb responses accompanying standing human leg flexion movements. AB - The organization of electromyographic (EMG) and kinetic (ground reaction forces) responses in postural (single stance limb) and primary task (flexing limb) components was examined in standing human subjects during single leg flexion movements over a range of speeds. Interlimb responses occurred coincidently prior to unloading and were scaled as a function of movement speed, suggesting a centrally organized, synchronous mode of coordination which reflected the mechanical constraints related to stance support function. PMID- 1628224 TI - Treatment of advanced colorectal cancer with recombinant interferon alpha and fluorouracil: activity in liver metastasis. AB - A cohort of 35 patients with advanced colorectal cancer, not previously exposed to chemotherapy, were included in a phase II study exploring the combination of interferon-alpha, 9 MU subcutaneously three times weekly, and 5-fluorouracil 750 mg/m2/day during 5 consecutive days in continuous intravenous infusion followed with weekly bolus injection of fluorouracil 750 mg/m2. Of 33 cases evaluable for activity; 5 patients achieved partial response and 3 complete response for an overall response rate of 24% (95%; confidence limit 11-42%). Most of the responses were observed in liver metastases, response rate = 30% (95%; CL 13 53%), with little activity observed in other sites; response rate 3% (95%; CL 8 16%), p = .0006. The median time to progression and median overall survival were 16+ (range 1+ to 48+) and 21+ weeks (range 1+ to 52+). All patients were evaluable for analysis of toxicity. Severe mucositis and diarrhea, present in 14 patients were the limiting side effects. Two patients developed progressive renal toxicity and died. Weakness, myalgia, and nonneutropenic fever were observed frequently, one patient developed dementia. This combination is able to induce major responses in patients with advanced colorectal cancer, particularly in liver metastasis. Additional trials evaluating this approach are indicated. PMID- 1628225 TI - Preliminary evidence that incorporation of 5-fluorouracil into RNA correlates with antitumor response. AB - A comparative study of two different species of a fluorouracil assay was conducted on 11 patients who had carcinoma that was deemed unresectable after the surgical operation. For these patients FU at a dose of 10 mg/kg was intravenously administered before operation, and portions of the tumors were resected within 120-150 min to assay both the (FU)RNA/RNA and FU/protein. After surgery, all patients were given FU alone either intravenously or orally. The FU, which was in an acid-soluble material (FU/protein), was not related to the antitumor effect of FU. However, the FU in RNA [(FU)RNA/RNA)] was found to be related to the antitumor effect of FU. When the concentration of (FU)RNA/RNA was above approximately 200 ng/mg, FU was effectual in unresectable carcinomas. It is probable that the (FU)RNA/RNA may be more suitable than FU/protein for predicting the antitumor effect of FU. PMID- 1628226 TI - Treatment with ImuVert/N-acetylcysteine protects rats from cyclophosphamide/cytarabine-induced alopecia. AB - Chemotherapy-induced alopecia is a distressing problem to the cancer patient for which currently there is no effective preventive measure. Recently ImuVert, a biologic response modifier, has been shown to protect from cytarabine-induced alopecia in the young rat model, but not from alopecia induced by cyclophosphamide. In the present study, the rat model was used to examine the effect of N-acetylcysteine on the course of alopecia from cyclophosphamide and of ImuVert plus N-acetylcysteine on alopecia induced by cytarabine-cyclophosphamide combination. The following observations were made: (1) Cyclophosphamide-induced alopecia could be effectively prevented by N-acetylcysteine, administered parenterally or applied topically in liposomes. (2) Alopecia caused by the combination of cyclophosphamide and cytarabine could be prevented by the parenteral or topical administration of ImuVert plus N-acetylcysteine. The potential applicability of these observations to the clinical settings remains to be determined. PMID- 1628227 TI - Hyperthermic isolation limb perfusion for malignant melanoma: a review. PMID- 1628228 TI - Treatment of intractable dyspnea: clinical and ethical issues. PMID- 1628229 TI - Oncology drug discovery and clinical trial testing: who's listening? PMID- 1628230 TI - [The laryngeal mask]. AB - The laryngeal mask (LM) is a new concept developed by Brain. Easily inserted, the LM allows appropriate ventilation without the disadvantages of either the facial mask or the endotracheal intubation with its own complications. The limits of its use concern all the cases of reduction of thoracopulmonary compliance and full stomach. The LM offers no protection against regurgitation and aspiration. Airway obstruction may occur following laryngospasm (light anaesthesia) or down folding of the epiglottis. Trauma to the uvula and the posterior pharyngeal wall have been reported. The LM may be useful in all cases of surgery in which intubation is not absolutely required. Moreover, the LM is widely used for ENT and ophthalmic surgeries, in paediatric and adult procedures. Many cases of foreseeable or unforeseeable difficult intubation have been resolved by the insertion of a LM, allowing secondary intubation through the mask. Further investigations are required in order to evaluate the real limits and indications for its extended use. PMID- 1628231 TI - [Regional anesthesia by the caudal route in adults. Apropos of 56 caudal blocks]. AB - Caudal anaesthesia was described in 1901 but is now essentially used for paediatric surgery. From their experience of 56 caudal blocks in adult patients scheduled for pelvic surgery or endoscopy, the authors discuss the value of this technique. The anatomical and physiological basis and the main guidelines of caudal anaesthesia are recalled through some references. PMID- 1628232 TI - [The computerized anesthesia record]. AB - The first anaesthetic record was introduced into medical practice in 1940. Since then few changes have been made to it and it remains a rudimentary memorandum. However, since the beginning of the 1980s, interest in automatic recording of the anaesthetic file has been increasing and numerous arguments can be put forward in its favour. Apart from theoretical and experimental arguments, in practice one has to master the automatic collection of data, management of alarms and the technology of the networks involved in order to manage the flow of information by channelling it and organizing it into a hierarchy. Four other objectives can be added to the clinical recording and its medico-legal applications: anaesthetic cost evaluation, quality of care, research and clinical teaching which will provide the basis of anaesthetic epidemiological research. PMID- 1628233 TI - [Poisoning by buflomedil (Fonzylane)]. PMID- 1628234 TI - [The use of the laryngeal mask in a case of difficult intubation]. PMID- 1628235 TI - [Coma during a hip prosthesis under spinal anesthesia. Apropos of a case]. AB - A case is reported of a postoperative coma in a ASA I 79 years old patient undergoing a spinal anaesthesia for hip prosthesis. The complication occurred three hours after the subarachnoidal puncture and 90 minutes after the completion of surgery. A complete recovery was observed in the following 48 hrs with the help of symptomatic treatments. Possible aetiologies and mechanisms of such accidents are discussed. However no definite cause could be ascertained in the case reported above, which is to add to similar ones observed during spinal anaesthesia in healthy patients. Anyhow, close surveillance is always mandatory. PMID- 1628236 TI - [Can anesthesiologists really have control over the preoperative examination?]. PMID- 1628237 TI - [The debut of ether anesthesia in Germany]. PMID- 1628239 TI - [Minimum alveolar concentration?]. PMID- 1628238 TI - [Four cases of cardio-circulatory inefficacy during anesthesia: the role of propofol?]. PMID- 1628240 TI - [The reliability of slow flow isoflurane vaporizers]. AB - Two new vaporizers for isoflurane were tested and verified with very low flows: Ohmeda Tec 5 and Penlon PPV Sigma vaporizers. This work completes a previous one [1]. The Ohmeda Tec 5 appeared to be quite reliable. The Penlon vaporizer gave pretty good results too. However a gas flow with vibratory component can affect the result by decreasing dramatically the concentration of inhaled isoflurane. PMID- 1628241 TI - [A comparative study of CPK during spinal surgery in the knee-chest position. Apropos of 93 patients]. AB - A number of severe rhabdomyolysis with acute renal failure have been reported following spine surgery in knee chest position. CPK were measured postoperatively in 93 patients (A group), comparatively with two groups in which respectively neurosurgery without any muscle stretching (B group) and abdominal surgery with aid of retractors (C group) were performed. CPK were significantly and similarly increased in A and C groups only. This postoperative increase of CPK appears to be related more to the muscle stretching than to the posture itself. Intraoperative low blood pressure and an operating time longer than 4 hrs contribute probably to rhabdomyolysis. No renal failure was observed in our series. Low limb vascular insufficiency is the main contra-indication of knee chest position. Postoperative diuresis surveillance is mandatory in all cases, CPK analysis is not. PMID- 1628242 TI - [Anesthesia in the schizophrenic]. AB - The preanaesthetic interview and examination is difficult in case of schizophrenia. The lack of communication can be responsible for late recognition of surgical diseases. The treatment by neuroleptic drugs should not be interrupted. It can interfere with anaesthesia, yet all anaesthetic methods can be safely used including local and regional anaesthesia to be performed under sedation. Postoperative care requires psychiatric nursing staff and is often rendered difficult by the patients agitated behaviour. In catatonic schizophrenia it can be difficult to diagnose a malignant syndrome of neuroleptics. Peristaltis is slowed by neuroleptic and antiparkinson drugs and pseudoileus may occur. Appropriate medical treatment to evacuate the bowels is needed. PMID- 1628243 TI - The pathophysiology of pain. AB - Attempting to relieve pain can be difficult, but with a firm understanding of the physiology of pain facilitation and inhibition, meaningful management strategies can be devised. Pain management failure will be more easily understood and less likely to be blamed on the patient. Good pain management requires both the practitioner and the patient to be knowledgeable. There are no shortcuts or prescriptions that will suit every patient experiencing any particular type of pain. This fact is both the difficult dilemma and the challenging aspect of pain control. PMID- 1628244 TI - Assessment and management of pain in the critically ill trauma patient. PMID- 1628245 TI - Pediatric pain management. AB - The management of pediatric pain is a complex, multifaceted subject. By viewing pediatric pain management as a priority, health care providers may diminish children's suffering in hospital settings. Critical care nurses can make a difference by increasing awareness of pain issues, incorporating pain assessment tools into their flow sheet, being knowledgeable about pain management interventions, and collaborating with the other health care team members to cope effectively with each child's individual pain management needs. PMID- 1628246 TI - Discomfort to environmental noise: heart rate responses of SICU patients. PMID- 1628247 TI - Diagnosing asthma by questionnaire in epidemiological surveys. PMID- 1628248 TI - The bronchial epithelium as a target for inflammatory attack in asthma. PMID- 1628249 TI - An update on PAF. PMID- 1628250 TI - A research method to induce and examine a mild exacerbation of asthma by withdrawal of inhaled corticosteroid. AB - This study evaluated a research method to examine an exacerbation of asthma induced by corticosteroid withdrawal. Ten non-smoking adult asthmatics who were stable on treatment with inhaled steroid underwent a graded reduction of the daily dose by 200 micrograms at weekly intervals until an exacerbation of symptoms occurred. A daily symptom, peak expiratory flow rate (PEF) and medication diary was kept. Weekly clinic visits were used to assess symptoms, spirometry, methacholine airway responsiveness (expressed as the provocative concentration to cause a fall in FEV1 of 20%, PC20), circulating eosinophils, basophils and their progenitors (Eo/B-CFU), and sputum inflammatory cells. The laboratory tests were performed blind to the clinical details. Each subject developed an exacerbation of symptoms, on average at 16 (7-26) days after the onset of steroid reduction. This was accompanied by a deterioration in each of the objective measures. There was a fall in FEV1 by 320 ml (s.e.m. 9.5) and in PC20 from 0.8 to 0.43 mg/ml. Circulating eosinophils rose from 114 (24) x 10(3)/ml to 227 (50) x 10(3)/ml and Eo/B-CFU rose from 31 (5.6) to 44 (11.3)/10(6) cells. Sputum developed in five subjects and contained 36 (5.2)% eosinophils and 1.98 (0.21)% metachromatic cells (mast cells or basophils). The symptom diary and weekly questionnaire were demonstrated to be valid and responsive to change. A deterioration indicated by the daily symptom score preceded changes in PEF. Treatment by an increase in steroid was followed by reversal of each of the changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628251 TI - The house dust mite Dermatophagoides pteronyssinus is the most important allergen on the island of Mauritius. AB - To determine the relative importance of mites as a cause of allergic sensitivity and asthma on the western Indian Ocean island of Mauritius, we measured specific IgE antibodies to common inhalant allergens in sera from Mauritians claiming to have allergic symptoms and we examined house dust samples for evidence of mites and their allergens. Seventy-two of the 110 sera tested (65%) contained detectable IgE antibody to at least one mite, mould or pollen allergenic extract. By far the most prevalent was antibody to one or both of the common house dust mites, Dermatophagoides pteronyssinus and Dermatophagoides farinae, being present in 67 (61%) of the 110 sera. Allergy to pollens, including the locally prevalent Bermuda grass and sugar cane, was infrequent. Antibody to a limited number of moulds was detected in 22% of the sera tested. Of 81 subjects whose clinical history was known, 60 were asthmatic, and 75% of these asthmatic individuals had IgE antibody to mites. In contrast, only 35% of the subjects with rhinitis without asthma were sensitive to mites. Different mite species, including D. pteronyssinus but not D. farinae, were identified microscopically in samples of local house dust. Mite antigen Der p I but not antigen Der f I was detected with specific monoclonal antibodies in extracts of these dust samples. On the bases of this serological and environmental survey, we conclude that our data support the hypothesis that the house dust mite D. pteronyssinus is the principal cause of allergic sensitivity and asthma in that tropical environment. PMID- 1628252 TI - Prediction of annual variations in atmospheric concentrations of grass pollen. A method based on meteorological factors and grain crop estimates. AB - We performed an aerobiologic observation of the grasses present in Madrid for 14 years (1978-1991), using volumetric air samplers. The counts obtained show that the major grass pollen release period (average daily grass pollen counts greater than 50 grains/m3 of air) occurs in the months of May and June, although lower counts can occur some days from the end of January onward. There are wide year-to year variations in total atmospheric grass pollen counts, expressed as the total sum of the mean daily concentrations from April 1st to July 30th (ranging from 2568 to 6624). A strong, statistically significant correlation, based on Spearman's rank test and/or simple and multiple linear regressions, was found between the total grass seasonal count and preseasonal rainfall from October to March (R2 = 0.64; P = 0.0429). The meteorological variable which gave the correlation with greatest statistical significance (R2 = 0.97; P = 0.0016) was the average monthly preseasonal humidity from October to March. A good correlation was also found between March estimates of wheat, rye and barley crops and the total grass count (R2 = 0.73; P = 0.006). A model was designed from the above mentioned humidity variable through a multilinear regression analysis, and it was possible to predict, at the beginning of April, total seasonal counts for 1989 (predicted = 5468; actual = 4410; average error = 24%), 1990 (5033; 6090; 17%) and 1991 (3930; 2568; 53%). These data may help clinicians to predict and prepare themselves for the intensity of the grass pollen season and to explain yearly variations in the severity of symptoms. PMID- 1628253 TI - Monoclonal antibodies bind identically to both spores and hyphae of Aspergillus fumigatus. AB - Immunoelectron microscopy (IEM) was used to determine the binding of six monoclonal antibodies (MoAbs) produced against Aspergillus fumigatus antigens present on or within the conidia and hyphae of the fungus. Antigen-antibody complexes were demonstrated in EM using labelled colloidal gold particles (15 nm). Three out of 6 MoAbs (C9, F12 and H10) reacted only with the cytoplasmic components of A. fumigatus while the remaining three (B12, F6G5 and D6E6) showed reactivity to both cytoplasm and cell wall of the conidia and hyphae. The results indicate that IEM is of considerable value in determining and selecting monoclonal antibodies having specific reactivity with diverse antigenic components. PMID- 1628254 TI - Comparison of a video questionnaire with the IUATLD written questionnaire for measuring asthma prevalence. AB - A video questionnaire (VQ) for measuring asthma prevalence in adolescents was assessed for repeatability and validity in relation to bronchial hyperresponsiveness (BHR) (PD20 less than or equal to 7.8 mumol methacholine). Comparison was also made with a standard, self completed written questionnaire (SQ), based on the IUATLD Bronchial Symptoms Questionnaire, which included five questions seeking comparable data to those in the VQ. Both the VQ and SQ were administered to 707 schoolchildren (13-16 years), in whom English was the primary language. One hundred and six randomly selected children subsequently underwent bronchial challenge to methacholine. Both the sensitivity and specificity for BHR were higher for a combination of three or more positive responses to the VQ (0.73 and 0.88), than to the SQ (0.63 and 0.82), although these differences were not statistically significant (P = 0.24). When administered again after a two week interval, the VQ had a significantly higher (P = 0.03) coefficient of repeatability (0.79) than the SQ (0.50). We conclude that the VQ is a valid and reliable method of determining asthma prevalence, and propose that by providing data relatively free from biases due to language, culture, literacy or interviewing techniques it may be particularly useful when comparing asthma prevalence and severity in different populations. PMID- 1628255 TI - Can fatal asthma be prevented?--a personal view. AB - An increase in the mortality rate from asthma in several countries has been observed in recent years, notwithstanding the great improvement in pathophysiological findings and the introduction of new effective therapeutic agents. The phenomenon is difficult to explain but the causes of death and identification of high-risk patients have been widely studied. It is suggested that the most vital aim for physicians is the avoidance of those factors which may contribute to death from asthma. These are particularly: inadequate assessment of its severity by patients, general practitioners and hospital doctors, and inadequate and inappropriate treatment. From the diagnostic point of view, the measurement of airflow rates is necessary to establish the diagnosis in terms of reversibility, quantify the severity and assess the response to therapy. The different entity of reversibility of bronchial obstruction is due to the various mechanisms intervening in different patients. After adequate treatment, according to our observations, the reversibility is more complete in young people and when the duration of the disease is less than 2 years. Trigger factors must also be considered. From the therapeutic point of view, considering that the most important alteration in asthma is the inflammation of bronchial structures with intervention of several inflammatory cells and of numerous different chemical mediators, physicians have to apply treatment aimed at reducing inflammation rather than relying on symptomatic bronchodilator remedies. Treatment should be divided into three phases, according to symptoms: induction, consolidation and maintenance. Finally, on the basis of data here presented and of clinical experience, the essential measures for the prevention of asthma mortality are reported. If general practitioners take them into account, deaths from asthma will be reduced to a minimum. PMID- 1628256 TI - Magnification. PMID- 1628257 TI - Malignant hyperthermia. PMID- 1628258 TI - Clindamycin and dry socket. PMID- 1628259 TI - Concerns regarding infection control recommendations for dental practice. AB - It goes without saying that the members of any professional group are more likely to modify their behavior if they are provided with logical, rational reasons to enact the suggested change. In the mid 1980s, health care providers, including dental personnel, were advised to adopt universal precautions and to alter their infection control habits with minimal justification, apart from the general unease and paranoia surrounding AIDS. Therefore, it is understandable that some practitioners would react with scepticism to the idea that their traditional infection control techniques were less than adequate, while others would overwhelmingly embrace the new recommendations in the misguided belief that personal, patient, staff and family safety would be enhanced. This predictable confusion is epitomized by the dentist who "sterilizes" extraction forceps by immersing them in alcohol for 10 minutes, versus the dentist who wears gloves, mask and disposable gown to conduct a recall examination. And if dentists are perplexed, it is clear that their staffs are equally, if not more confused, since they are exposed to the exaggerated claims and counter claims of sales agents. The microbes encountered in dental practise, apart from the hepatitis B virus, pose no significant risk to dental personnel or their patients, and the danger of hepatitis B transmission is reduced most effectively by vaccination. In reality, the genesis of dentistry's current emphasis on infection control resides entirely with HIV disease. But there is no credible clinical evidence to suggest that HIV infection is transmitted via dental treatment. Indeed, it may be theorized that for such a transmission to occur, the blood stream of the susceptible recipient would have to be invaded directly by a pathogenic inoculum of the virus--an unlikely event in the normal practise of dentistry. Under such circumstances, infection control practises should ignore the danger of HIV transmission, but concentrate on: Sterilization of all surgical and invasive instruments to protect patients from potential cross-infection. All dental staff receiving hepatitis B vaccinations. Dental staff wearing gloves, especially while performing intraoral procedures with blood release, and handling used instruments, to protect them from direct contact with potential pathogens. Working in a clean environment, in which blood spills and splatters are removed mainly for esthetic reasons. Such measures reflect the actual potential for disease transmission, as it exists in dentistry. They are justified and economical, and will be implemented by concerned but knowledgeable dental staff. PMID- 1628260 TI - Dentists overcome AIDS rumors. PMID- 1628261 TI - Another perspective of AIDS. PMID- 1628262 TI - Dental anesthesia and shoplifting: a case study. PMID- 1628263 TI - Naproxen: pharmacology and dental therapeutics. AB - Naproxen and naproxen sodium are very commonly used and effective non-steroidal anti-inflammatory analgesics. In this paper, they are described and compared, and their pharmacokinetics and indications are discussed. Adverse reactions to these drugs and the mechanism of action of these effects on the gastrointestinal tract, central nervous system, kidneys, liver, and blood are described. A discussion of the effects of the drugs on the elderly and during pregnancy and lactation is included. Also, the allergenicity, miscellaneous rare complications and acute toxicity of the naproxen anion are described, followed by a description of the more common drug interactions. The results of several recent studies that may call into question the current recommendations on using these pharmaceuticals are cited. Until this controversy can be resolved, the practitioner should rely on the principle of "first do no harm" in choosing a course of drug treatment. PMID- 1628264 TI - Factors influencing repair and regeneration following replantation. PMID- 1628265 TI - Vertical extrusion: literature review and report of a case. AB - To date, the scientific literature has documented, primarily, successful methods and techniques of treatment involving vertical extrusion. The purpose of this article is to review the literature and report on a case that demonstrates the multidisciplinary approach required to successfully manage a reversible complication involving the restoration of an adult maxillary central incisor that had sustained an oblique crown-root fracture. PMID- 1628266 TI - [Adhesive resistance between a polymerizable glass ionomer base (Vitrabond) and a composite resin (P 50)]. AB - This study attempts to measure the adhesive resistance between VitreBond and P-50 composite resin when the VitreBond surface is submitted to grinding and to the application of Scotchprep. The results indicate that this adhesion is superior to the cohesive resistance of VitreBond independently from grinding and from the application of Scotchprep. PMID- 1628267 TI - Evaluation of the hypertensive child. PMID- 1628268 TI - Hypertension in the neonatal period. PMID- 1628269 TI - Essential hypertension in childhood and adolescence. PMID- 1628270 TI - Coarctation of the aorta and hypertension. PMID- 1628271 TI - Hypertension in the child with chronic renal insufficiency or undergoing dialysis. PMID- 1628272 TI - Pediatric post-transplant hypertension: a review of current standards of care. PMID- 1628273 TI - Surgical intervention in pediatric renovascular hypertension. PMID- 1628274 TI - Pediatric hypertension. PMID- 1628275 TI - Physiology of blood pressure. PMID- 1628276 TI - Na-Li countertransport and blood pressure in childhood. PMID- 1628277 TI - Normal and abnormal blood pressure in childhood. PMID- 1628278 TI - Diet, salt, anthropological and hereditary factors in hypertension. PMID- 1628279 TI - Treatment of experimentally induced atherosclerosis in swine iliac arteries: a comparison of self-expanding and balloon-expanded stents. AB - Atherosclerosis was induced in 20 Hanford miniature swine. Subsequently, one iliac artery lesion in each of 16 pigs was stented with either a self-expanding (8 pigs) or a balloon-expanded (8 pigs) stent. Immediately after stent placement, 4 animals in each group were taken off the atherogenic diet and continued on normal chow for the remainder of the study. Four months after stents were placed, atherosclerosis and the mural changes associated with the stent were more clearly evident in the arteries of the pigs continued on the atherogenic diet. These pigs also exhibited significantly more neointimal proliferation. In addition, the arteries containing the balloon-expanded stents showed more extensive and complex intimal changes when compared with arteries with self-expanding stents. Although both stent designs were equally effective in maintaining vascular patency, the balloon-expanded stent was more traumatic to the vessel wall which resulted in a significantly greater neointimal thickness. PMID- 1628280 TI - Oscillating probe aspiration thrombectomy: comparative in vitro evaluation of two concepts. AB - Aspiration thrombectomy supported by an oscillating metal probe within the catheter allows continuous aspiration of large thrombi without catheter obstruction. Thrombus aspiration assisted by an ultrasound-driven probe (frequency 26 kHz) and by an electric motor-driven probe (frequency 40 Hz) was compared in two different in vitro models: aspiration of large clots from a Petri dish and recanalization of thrombotic occlusions in a flow model. Comparable results were found for a 1 mm ultrasound-driven probe and a 0.5 mm motor-driven probe. The motor-driven device, however, seems to be more appealing for in vivo application because of its simplicity, probe flexibility, absence of thermal effects, and low cost. PMID- 1628281 TI - Bronchial artery embolization for hemoptysis: immediate and long-term results. AB - The purpose of this study was to evaluate the immediate and long-term results in 63 patients who underwent transarterial embolization for control of hemoptysis. Overall immediate success rate was 86.1%. At long-term follow-up 50% of patients showed complete remission, 22% partial remission, and 28% recurrent hemoptysis. Hemoptysis remained controlled for a mean of 22 months and a median of 14 months. The long-term results among four disease groups differed substantially. Patients with bronchiectasis showed the best results, followed by those with idiopathic disease and with inflammation; patients with neoplasm showed the worst results. PMID- 1628282 TI - Pulmonary arteriography. AB - Developments in catheter design, contrast media, and radiologic equipment have simplified the performance of pulmonary arteriography. With proper precautions the procedure is acceptably safe even in critically ill patients. This procedure should be part of the repertoire of any active and properly equipped angiographic laboratory. PMID- 1628283 TI - Selecting the right technique to reform a reverse curve catheter (Simmons style): critical review. AB - Reformation of the curve of the Simmons sidewinder catheter may be difficult in some patients, and the originally described technique using the left subclavian artery may be unsuccessful. We review the techniques available for curve reformation, identifying the limitations and problems associated with each technique. We believe that reformation in the descending aorta without a guidewire is the method of choice in most patients. Knowledge of a number of different techniques is advisable. PMID- 1628284 TI - Spontaneous splenic rupture associated with thrombolytic therapy and/or concomitant heparin anticoagulation. AB - Two cases of spontaneous splenic rupture in connection with thrombolytic therapy and concomitant heparin anticoagulation are reported. One patient was being treated for peripheral arterial graft occlusion using intraarterial urokinase, the other received intravenous infusion of streptokinase for acute myocardial infarction. Neither patient had a condition predisposing to splenic rupture. Although rare, previous reports of spontaneous splenic rupture associated with thrombolytic therapy and/or anticoagulation have been reported. Splenic rupture as a complication of thrombolytic therapy and/or anticoagulation should be considered when unexplained abdominal symptoms, hypotension, or blood loss is encountered. PMID- 1628285 TI - Focal necrosis of the ureter following CT-guided chemical sympathectomy. AB - Focal necrosis of the ureter was observed in our patient 7 days after CT-guided chemical sympathectomy. The injection of phenol was apparently rendered remote from the ureter and still caused ureteric necrosis. Ureteric injury may thus result following chemical sympathectomy, not from direct puncture of the ureter, but from unpredictable individual diffusion pathways. PMID- 1628286 TI - Percutaneous fenestration of a type I aortic dissection for relief of lower extremity ischemia. AB - A 36-year-old patient underwent successful percutaneous fenestration of a type I aortic dissection which had caused occlusion of the right common iliac artery and ischemia of the right lower extremity. The patient is currently (6 months post fenestration) ambulating without any signs of vascular compromise. The technique may be useful in patients who are at high risk for surgical procedures. PMID- 1628287 TI - Retrograde esophageal balloon dilatation: salvage treatment of caustic-induced stricture. AB - A 14-month-old boy with severe esophageal strictures following ingestion of potassium hydroxide is described. Initially, treatment was by surgical bougienage but following esophageal perforation, 65 balloon dilatations were performed over an 8-month period using a retrograde approach via a feeding gastrostomy without anesthesia or sedation. A further nine dilatations in the following 6 months were performed using a per-oral approach after establishment of full oral nutrition and removal of the gastrostomy. The main advantage of the retrograde approach was the large number of dilatations that could be performed without anesthesia in an infant. This has allowed nonoperative treatment of a high grade caustic esophageal stricture which would otherwise have required esophageal replacement. PMID- 1628288 TI - Subaortic aneurysm in a case of aortic coarctation: case report. AB - Subaortic aneurysms are very rare and of uncertain etiology. We present a unique case in which coarctation of the aorta and biscuspid valve predisposed to infective endocarditis and formation of a mycotic subaortic aneurysm. PMID- 1628289 TI - Human root caries: histopathology of arrested lesions. AB - The histopathology of arrested root caries lesions was examined in extracted human teeth. The main structural characteristics of arrested lesions were the completely mineralized surface area and the formation of a distinct sclerosis of the dentinal tubules. Intertubular dentin was, with the exception of the dentinal tubules, fully mineralized up to the surface. Dentinal tubules near the surface were either filled with ghosts of microorganisms or with crystals of different shapes. Sclerosis of the dentinal tubules was characterized by the presence of three different patterns of intratubular mineralization that occur in distinct regions of the zone of tubular sclerosis. The patterns were distinguishable by the type of crystals and their association with organic structures such as collagenous fibrils or odontoblast processes. It is suggested that arrested lesions are based on (1) the formation of an inner barrier that interrupts the diffusion of substrata from the pulp to invaded bacteria, (2) the formation of an outer barrier by a compact, highly mineralized surface region which blocks the diffusion of products of bacterial metabolism into dentin, and (3) an area of mineralization which extends from the outer barrier toward the root canal within demineralized dentin. The present study demonstrates the considerable potential of caries lesions in dentin to become arrested, and subsequently partially remineralized. These phenomena seem to depend on the severity of an active lesion and its location on the root surface. This should be taken into account when diagnosing root caries lesions. The potential of root caries lesions to become arrested indicates that the treatment concept of active root caries lesions should be reconsidered. PMID- 1628290 TI - Increased resistance to artificial caries-like lesions in dentin treated with CO2 laser. AB - The crowns of 60 permanent human molars were sectioned transversally. The exposed dentin surface was divided into different parts: a first part was kept as control, a second part was immediately varnished, and a third part was irradiated with a CO2 laser using the same irradiation conditions as those applied for caries removal (10 impulses of the same energy; 0.2 s/impulse; energy density/impulse 280-715 J/cm2. After irradiation, a small portion of this area was varnished. The teeth were immersed for 4 weeks in a cariogenic gel (pH = 4.5) at 36 degrees C. Twenty teeth were studied by scanning electron microscopy, and longitudinal sections of the other teeth were prepared for microradiography and microdensitometry measurements. The lased dentin surface appeared smooth for energy densities lower than 425 J/cm2. Longitudinally fractured samples revealed a layer of dentin devoid of tubular structure (20-70 microns thick, depending on the energy density used), whereas below the sealed layer, the dentinal tubules retained their normal aspect. Although the sealed layer showed no demineralization when exposed to acid, demineralization of the underlying dentin occurred, but to a much lesser extent than in the unlased dentin. PMID- 1628291 TI - Effects of nine different chewing-gums and lozenges on salivary flow rate and pH. AB - The objectives of this study were to determine how salivary flow rate and pH vary with time during use of chewing-gums and lozenges. Twenty-four young adults collected unstimulated saliva and then, on different occasions, chewed one of six flavoured gums, or gum base, or sucked on one of two lozenges, for 20 min, during which time eight separate saliva samples were collected. Flow rate peaked during the 1st minute of stimulation with all nine products. With the lozenges, flow rate fell towards the unstimulated rate when the lozenges had dissolved. There were no significant differences in the flow rates elicited by cinnamon- or peppermint-flavoured gums or between sugar-containing or sugar-free gums. With the flavoured gums, the mean flow rate followed a power curve (r = -0.992) with time and within about 10 min was not significantly different from that when gum base was the stimulus. The initial stimulated flow rate with flavoured gums was about 10-12 times greater than the unstimulated rate (0.47 ml/min). After 20 min of chewing, it was still about 2.7 times that rate and about the same as the flow rate elicited by chewing-gum base alone. The pH of unstimulated saliva was about 6.95. With one gum containing about 1.5% organic acids, the salivary pH fell to a minimum of 6.18 in the 1st minute of stimulation, but then rose rapidly to a level above that in unstimulated saliva. With a sucrose-containing and a sucrose free gum, the pH rose immediately on stimulation and then fell slightly with time to levels which were significantly above the pH of unstimulated saliva. PMID- 1628292 TI - Mutans streptococci and lactobacilli in breast-fed children with rampant caries. AB - This study aimed to investigate the prevalence of selected components of the oral microflora in breast-fed children who developed rampant caries (resembling nursing caries) under hitherto unexplained circumstances. Dental plaque and saliva samples were collected from breast-fed children, aged between 1 and 2.5 years, with and without rampant caries. Mutans streptococci and lactobacilli were isolated from dental plaque of all children with rampant caries and from most caries-free children. None of the colonies of mutans streptococci resembled those of Streptococcus sobrinus. The mean counts of the mutans streptococci and lactobacilli were 100-fold higher in plaque samples from children with rampant caries as compared with caries-free children. No difference could be found between the numbers of mutans streptococci in plaque overlaying cavities and that from adjacent sound enamel. In contrast, the counts of lactobacilli in plaque were approximately 100-fold higher from cavities than from sound surfaces. The levels of mutans streptococci in saliva were directly related to the presence of rampant caries. The results show that caries-free and caries-active breast-fed children, aged 1 to 2.5 years, harbour mutans streptococci and lactobacilli on their teeth. Rampant caries in these children can occur in the absence of nursing bottles or any other feeding abuse during weaning and in the presence of an aciduric plaque microflora, as has been reported for children with nursing bottle caries. PMID- 1628293 TI - Validity of diagnosis of questionable caries lesions in occlusal surfaces of extracted third molars. AB - This study was to evaluate the accuracy of visual inspection, conventional radiography, and digital radiographic methods for the detection of occlusal carious lesions in third molars from a present-day adolescent population. Seventy eight third molars, considered clinically to be without occlusal cavities, were extracted from young soldiers. Before extraction, an intra-oral radiograph was obtained. After extraction, the teeth were examined visually as per the criteria: 0 = no caries, 1 = chalky/stained fissure indicative of enamel caries, 2 = chalky and dark-stained fissure considered indicative of a dentinal lesion, and 3 = as per criterion 2, but with small surface defects (microcavities). The radiographs were digitised, and image enhancement with contrast stretch and a filtering procedure was performed, respectively. The three types of radiographic image were assessed as per the criteria: 1 = no caries/caries confined to enamel, 2 = caries involving the outermost dentine, and 3 = deep dentinal caries extending half-way or more to the pulp. Ground sections (500-600 microns in thickness) served as validation for lesion depth. The digital radiographic method with contrast stretch performed overall best of the four methods (greater than 70% detection rate) while visual inspection (53% detection rate) performed better than conventional radiography (48% detection rate). When results from visual inspection and conventional radiography were combined, an increase in the detection rate of 11% was obtained with a 7% increase in false-positive scorings. When digitally contrast-manipulated radiographs were combined with visual inspection, a gain of 33% was obtained with an 11% increase in false positives.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628294 TI - The status of bite-wing radiographs in enhancing discriminatory ability in caries prophylactic clinical trials. AB - Data were taken from six randomised controlled trials of caries prophylactic agents in order to investigate the capacity of bite-wing radiographs of posterior approximal tooth surfaces to enhance discrimination between test and control group measurements. The findings showed that, where an active control agent was employed, the addition of radiographic to clinical examination data failed to improve discriminatory power in comparisons between 3-year caries increments. PMID- 1628295 TI - Caries prevalence of kindergarten children in Salzgitter and Oslo. AB - In a comparable epidemiological study of kindergarten children, 455 4- and 5-year olds in Salzgitter (FRG) and 171 4- and 5-year-olds in Oslo (Norway) were examined. Caries was scored at the cavitation level according to WHO criteria. The percentage of caries-free children was higher and the dmfs scores were lower in Oslo than in Salzgitter. It is postulated that this was the result of different levels of fluoride exposure, nutritional habits and dental treatment provision. PMID- 1628296 TI - Rampant caries and linear hypoplasia (short communication). PMID- 1628297 TI - Formation of neuroblastic layers in chicken retinospheroids: the fibre layer of Chievitz secludes AChE-positive cells from mitotic cells. AB - The significance of the classical subdivision of the retinal primitive neuroepithelium into an outer and an inner neuroblastic layer by the transient fibre layer of Chievitz (LOC) is little understood. We examine here the formation of neuroblastic layers by regenerating fully laminated retinospheroids from dissociated cells of the embryonic chick eye margin in rotary culture. By tracing cellular processes with the fibre-specific F11-antibody in retinospheroids, we occasionally find, in addition to an outer and an inner plexiform layer, a cell free F11-positive LOC homologue, subdividing the inner nuclear layer. Moreover, we demonstrate that the LOC precisely separates postmitotic AChE-positive cells of the inner retina from an AChE-negative outer part holding all BrdU-labelled mitotic cells. These in vitro data suggest that the inner neuroblastic layer is exclusively composed of AChE-positive cells, thus representing a primary differentiation zone of the retina. PMID- 1628298 TI - Chicken retinospheroids as developmental and pharmacological in vitro models: acetylcholinesterase is regulated by its own and by butyrylcholinesterase activity. AB - The phylo- and ontogenetically related enzymes butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) are expressed consecutively at the onset of avian neuronal differentiation. In order to investigate their possible co-regulation, we have studied the effect of highly selective inhibitors on each of the cholinesterases with respect to their expression in rotary cultures of the retina (retinospheroids) and stationary cultures of the embryonic chick tectum. Adding the irreversible BChE inhibitor iso-OMPA to reaggregating retinal cells has only slight morphological effects and fully inhibits BChE expression. Unexpectedly, iso-OMPA also suppresses the expression of AChE to 35%-60% of its control activity. Histochemically, this inhibition is most pronounced in fibrous regions. The release of AChE into the media of both types of cultures is inhibited by iso OMPA by more than 85%. Control experiments show that AChE suppression by the BChE inhibitor is only partially explainable by direct cross-inhibition of iso-OMPA on AChE. In contrast, the treatment of retinospheroids with the reversible AChE inhibitor BW284C51 first accelerates the expression of AChE and then leads to a rapid decay of the spheroids. After injection of BW284C51 into living embryos, we find that AChE is expressed prematurely in cells that normally express BChE. We conclude that the cellular expression of AChE is regulated by the amount of both active BChE and active AChE within neuronal tissues. Thus, direct interaction with classical cholinergic systems is indicated for the seemingly redundant BChE. PMID- 1628299 TI - Specialized ommatidia for polarization vision in the compound eye of cockchafers, Melolontha melolontha (Coleoptera, Scarabaeidae). AB - The superposition eye of the cockchafer, Melolontha melolontha, exhibits the typical features of many nocturnal and crepuscular scarabaeid beetles: the dioptric apparatus of each ommatidium consists of a thick corneal lens with a strong inner convexity attached to a crystalline cone, that is surrounded by two primary and 9-11 secondary pigment cells. The clear zone contains the unpigmented extensions of the secondary pigment cells, which surround the cell bodies of seven retinula (receptor) cells per ommatidium and a retinular tract formed by them. The seven-lobed fused rhabdoms are composed by the rhabdomeres of the receptor cells 1-7. The rhabdoms are optically separated from each other by a tracheal sheath around the retinulae. The orientation of the microvilli diverges in a fan-like fashion within each rhabdomere. The proximally situated retinula cell 8 does not form a rhabdomere. This standard form of ommatidium stands in contrast to another type of ommatidium found in the dorsal rim area of the eye. The dorsal rim ommatidia are characterized by the following anatomical specializations: (1) The corneal lenses are not clear but contain light scattering, bubble-like inclusions. (2) The rhabdom length is increased approximately by a factor of two. (3) The rhabdoms have unlobed shapes. (4) Within each rhabdomere the microvilli are parallel to each other. The microvilli of receptor 1 are oriented 90 degrees to those of receptors 2-7. (5) The tracheal sheaths around the retinulae are missing. These findings indicate that the photoreceptors of the dorsal rim area are strongly polarization sensitive and have large visual fields. In the dorsal rim ommatidia of other insects, functionally similar anatomical specializations have been found. In these species, the dorsal rim area of the eye was demonstrated to be the eye region that is responsible for the detection of polarized light. We suggest that the dorsal rim area of the cockchafer eye subserves the same function and that the beetles use the polarization pattern of the sky for orientation during their migrations. PMID- 1628300 TI - Immunocytochemical localization of beta-1,3-glucan recognition protein in the silkworm, Bombyx mori. AB - A monospecific antibody against beta-1,3-glucan recognition protein (a 62 kDa protein) of the larval silkworm prophenoloxidase activating system was used to study the localization of the protein. Among tissues from 5th instar larvae, only hemocytes and plasma were shown to contain a 62 kDa polypeptide immunoreactive with the antibody. Ultra-thin sections of the hemocytes were stained by an indirect immunogold staining method. Labelling occurred in the granules and cytoplasm of granulocytes and in the spherules and cytoplasm of spherulocytes. It was most conspicuous in granules of granulocytes and uniformly labelled spherules of spherulocyte, whereas no labelling was evident in prohemocytes, plasmatocytes and oenocytoids. The results are discussed in relation to the mode of recognition of fungi as non-self in insect hemocoel. PMID- 1628302 TI - Fine structure of the paracellular junctions of terminal villous capillaries in the perfused human placenta. AB - Selected lobules of human term placentae were extracorporeally perfused for a recovery period of 20 min, fixed by perfusion and mordanted with ferrocyanide prior to processing for transmission electron microscopy. The lateral membranes of the endothelial cells of the terminal villous capillaries were found to be separated by paracellular clefts of mean width 15.6 nm. At tight junctional regions (1-4 sites per cleft) the two membranes approached each other more closely and frequently appeared to fuse. However, tilting of the sections in the electron microscope stage showed that the membranes were separated by a gap of mean width 4.1 nm in at least 94% of tight junctional profiles. When individual tight junctions were studied by a combination of serial sectioning and goniometric tilting, they were seen to widen abruptly within a distance of three to seven consecutive thin sections, indicating they were not continuous throughout the axial length of the capillaries. The wide regions of the clefts usually showed linkers, strands of glycocalyx-like material spanning the gap. Linkers may contribute to cell adhesion and possibly form part of a filter within the tortuous paracellular pathway provided by the discontinuous network of tight junctional strands. Human term placental capillaries appear to resemble closely other continuous non-brain capillaries. PMID- 1628301 TI - Evaluation of mRNA steady-state and protein levels for basement membrane proteins in cultured murine cells. AB - We have determined the mRNA steady-state levels for the six constituent polypeptide chains of the basement membrane proteins collagen IV, laminin and nidogen in murine cell lines derived from a teratocarcinoma, and in some other cell lines of different origin in stationary cultures and during different growth phases. The mRNA and protein levels change in response to growth phase. The amounts of the mRNAs for the single chains do not agree with the ratios needed for the different peptide chains of collagen IV and laminin. While the mRNA and protein levels for laminin are in a similar range for the teratocarcinoma-derived cell lines, the mRNA and protein levels vary by at least a factor of 10 for collagen IV. These results point to complex posttranscriptional regulatory mechanisms for the biosynthesis of basement membrane proteins. PMID- 1628303 TI - Distribution of neuropeptide Y-like immunoreactivity in the brain and hypophysis of the cloudy dogfish, Scyliorhinus torazame. AB - Using a specific antiserum raised against synthetic neuropeptide Y, we examined the localization of immunoreactivity in the brain and hypophysis of the cloudy dogfish, Scyliorhinus torazame, by the peroxidase-antiperoxidase method. Immunoreactive perikarya were demonstrated in the ganglion of the nervus terminalis, the dorsocaudal portions of the pallium dorsale, the basal telencephalon, and the nucleus lateralis tuberis and the nucleus lobi lateralis in the hypothalamus. Labeled perikarya were also found in the tegmentum mesencephali, the corpus cerebelli, and the medulla oblongata. Some of the immunoreactive neurons in the hypothalamus were of the CSF-contacting type. The bulk of the labeled fibers in the nervus terminalis ran toward the basal telencephalon, showing radial projections and ramifications. Large numbers of these fibers coursed into the nucleus septi caudoventralis and the nucleus interstitialis commissurae anterioris, where they became varicose and occasionally formed fine networks or invested immunonegative perikarya. In the diencephalon, immunoreactive fibers were observed throughout the hypothalamus, e.g., in the pars neurointermedia of the hypophysis, the subependymal layer of the lobus inferior hypothalami, and in the neuropil of the posterior (mammillary) recess organ. Labeled fibers were scattered throughout the rest of the brain stem and were also seen in the granular layer of the cerebellum. These results suggest that, in the dogfish brain, neuropeptide Y or a related substance is involved in a variety of physiological processes in the brain, including the neuroendocrine control of the hypophysis. PMID- 1628304 TI - Coated vesicles are implicated in the post-fusion retrieval of the membrane of rat atrial secretory granules. AB - Using an in situ tannic acid perfusion technique, this study presents evidence that the removal of membrane components from the rat atrial secretory granule membrane after granule exocytosis is mediated by coated vesicles. When tannic acid is used to arrest the post-fusion stages of granule release, coated pit formation occurs on granule membrane, which, although continuous with the sarcolemma, is easily recognised by the membrane omega profile and the continued presence of the granule core. Tannic acid perfusion, before aldehyde fixation, allows a degree of continued cell function, and granule fusions can persist after tannic acid has reached the cell. This results in an increase in the numbers of fusion profiles and the appearance of coated pits on granule membrane at these sites. The proportion of granules with coats increases with perfusion time, suggesting that endocytotic, as well exocytotic events, may be arrested by the action of tannic acid. Coated vesicles are also involved at earlier stages of the release pathway. In other types of secretory system this is considered to represent recycling of membrane proteins as part of the maturation process of the granule. Although arrested granules exhibiting this clathrin coat could have had the coat prior to fusion, as part of the maturation process, our results show that it is more likely to represent a second stage of membrane protein recycling; the postfusion reclamation of proteins from the sarcolemma. This facet of the tannic acid perfusion procedure suggests a general method for quantifying coated pit formation during secretory granule release. PMID- 1628305 TI - Subcellular fractionation of rainbow trout gonads with emphasis on microsomal enzymes involved in steroid metabolism. AB - Rainbow trout gonads were subfractionated by differential centrifugation with emphasis on obtaining preparations suitable for the study of steroid-metabolizing enzymes. A fractionation scheme was evaluated for the mature testis and for 3 ovarian developmental stages. The distribution of cell organelles among the fractions was determined using enzyme-markers and electron microscopy. The fractionation scheme was found to be suitable for separating mitochondria and microsomes which were recovered at similar yields to those that had been reported for other extraheptic fish tissues. Fractionation of the mature ovary was fraught with problems probably because a large yolk protein cytosole fraction interfered with the recovery of microsomes. However, no difference in the specific activity of microsomal NADPH-cytochrome c-reductase between the various organ preparations was evident. The testis microsomes contained detectable amounts of cytochrome P450, whereas its content in the various ovary microsomes was too low to be detected. Progesterone 17 alpha-hydroxylase was detected in microsomes from testes and early developing ovaries, and microsomal aromatase activity was present in microsomes from early developing, mature and postovulatory ovaries. Furthermore, the testis microsomes contained a highly active UDP glucuronosyltransferase with testosterone used as a substrate. PMID- 1628306 TI - Immunocytochemical localization of collagen types I, III, IV, and fibronectin in the human dermis. Modifications with ageing. AB - The distribution of collagen types I, III, IV, and of fibronectin has been studied in the human dermis by light and electron-microscopic immunocytochemistry, using affinity purified primary antibodies and tetramethylrhodamine isothiocyanate-conjugated secondary antibodies. Type I collagen was present in all collagen fibers of both papillary and reticular dermis, but collagen fibrils, which could be resolved as discrete entities, were labeled with different intensity. Type III collagen codistributed with type I in the collagen fibers, besides being concentrated around blood vessels and skin appendages. Coexistence of type I and type III collagens in the collagen fibrils of the whole dermis was confirmed by ultrastructural double-labelling experiments using colloidal immunogold as a probe. Type IV collagen was detected in all basement membranes. Fibronectin was distributed in patches among collagen fibers and was associated with all basement membranes, while a weaker positive reaction was observed in collagen fibers. Ageing caused the thinning of collagen fibers, chiefly in the reticular dermis. The labeling pattern of both type I and III collagens did not change in skin samples from patients of up to 79 years of age, but immunoreactivity for type III collagen increased in comparison to younger skins. A loss of fibronectin, likely related to the decreased morphogenetic activity of tissues, was observed with age. PMID- 1628307 TI - Macrophage subpopulations and reticulum cells in rat placenta. An immunohistochemical study. AB - The placenta is a unique mixture of histoincompatible cells derived from mother and fetus. The aim of the present study was to obtain information on the development of macrophage subpopulations and reticulum cells during pregnancy in the placenta. Placentas of Wistar rats were removed at several stages of gestation, and were studied by immunohistochemical techniques applying monoclonal antibodies against macrophage subpopulations, lymphoid cells and reticulum cells. The expression of MHC class-II antigens was also studied. Throughout gestation macrophages were demonstrable in large numbers in the endometrium, in the myometrium and in the metrial gland, which is a compartment developing in the myometrium of pregnant rodents. In the labyrinth, a placenta compartment consisting of fetal cells, macrophages (probably of fetal origin) were already found on day 15. In the spongiotrophoblast and decidua basalis, which are layers of the placenta containing both maternal and fetal cells, only a few macrophages were recognized throughout gestation. The monoclonal antibody ED11, raised against reticulum cells, recognized fiber-like structures lining the blood sinuses of the spongiotrophoblast, in which only maternal blood is circulating. As the antigen recognized by ED11 is believed to play a role in the trapping of immune complexes, the spongiotrophoblast may play a role in the protection of the fetus from circulating immune complexes. PMID- 1628308 TI - Differentiation of smooth muscle cells in the fetal rat testis and ovary: localization of alkaline phosphatase, smooth muscle myosin, F-actin, and desmin. AB - The histochemical demonstration of alkaline phosphatase (AP) activity and localization of smooth muscle myosin (SMM), F-actin, and desmin were carried out on frozen sections of testes and ovaries from 15-day-old fetal to newborn rats. The presence of immunocytochemically localized SMM and desmin was confirmed by Western blot analysis of proteins from isolated gonads. The development of smooth muscle cells was predominant in the testis. The first SMM-positive cells with an increasing intensity for F-actin and desmin appeared in the testicular tunica albuginea and around the testicular cords by the age of 16 days. A continuous layer of SMM- and F-actin-positive (but not uniformly desmin-positive) myoid cells was detected in the newborn testis. In the early gonads and in the newborn ovary, a majority of the interstitial cells expressed desmin, indicating that, in undifferentiated tissues, non-myogenic cells may also express desmin. During fetal development, male and female gonocytes showed a decrease in F-actin content but retained their high AP activity. In the cortex of the newborn rat ovary, the observed high AP activity and the presence of desmin may be associated with the postnatal histogenesis of the follicles. The presence of SMM-containing cells in the hilus of the ovary may be required for the demarcation of the ovary from the mesonephros by the constriction of the mesovarium. The occurrence of SMM-positive cells predominantly in male fetuses suggests that the development of the contractile cells in the fetal testis may be induced by testicular androgens. PMID- 1628309 TI - Biogenesis of myeloid bodies in regenerating newt (Notophthalmus viridescens) retinal pigment epithelium. AB - Myeloid bodies are believed to be differentiated areas of smooth endoplasmic reticulum membranes, and they are found within the retinal pigment epithelium in a number of lower vertebrates. Previous studies demonstrated a correlation between phagocytosis of outer segment disc membranes and myeloid body numbers in the retinal pigment epithelium of the newt. To test the hypothesis that myeloid bodies are directly involved in outer segment lipid metabolism and to further characterize the origin and functional significance of these organelles, we examined the effects on myeloid bodies of eliminating the source of outer segment membrane lipids (neural retina removal) and of the subsequent return of outer segments (retinal regeneration) in the newt Notophthalmus viridescens. Light- and electron-microscopic analysis demonstrated that myeloid bodies disappeared from the pigment epithelium within six days of neural retina removal. By week 6 of regeneration, rudimentary photoreceptor outer segments were present but myeloid bodies were still absent. However, at this time, the smooth endoplasmic reticulum in some areas of the retinal pigment epithelial cells had become flattened, giving rise to small (0.5 micron long), two-to-four layer-thick lamellar units, which are myeloid body precursors. Small myeloid bodies were first observed one week later at week 7 of retinal regeneration. This study revealed that newt myeloid bodies are specialized areas of smooth endoplasmic reticulum. It also showed that a contact between functional photoreceptors and the retinal pigment epithelium is essential to the presence of myeloid bodies in the epithelial cells. PMID- 1628310 TI - Evidence for a morphological component in acid-base regulation during environmental hypercapnia in the brown bullhead (Ictalurus nebulosus). AB - Exposure of adult brown bullheads Ictalurus nebulosus (120-450 g) to environmental hypercapnia (2% carbon dioxide in air) and subsequent recovery caused transient changes in whole body net sodium flux (JnetNa+) and net chloride flux (JnetCl-) resulting largely from changes in whole body sodium influx (JNa+in) and chloride influx (JinCl-). Scanning electron microscopy (SEM) revealed that the fractional area of chloride cells (CCs) on the interlamellar regions was reduced by 95% during environmental hypercapnia. During post hypercapnic recovery, gill filament CC fractional area increased. The changes in JinCl- during and after environmental hypercapnia were closely associated with the changes in CC fractional area while the changes in JinNa+ did not correspond to the changes in CC fractional area. Transmission electron microscopy (TEM) supported the SEM observations of CC surface area changes and demonstrated that these changes were caused by covering/uncovering by adjacent pavement cells (PVCs). Lamellar and filament PVC microvilli density increased during hypercapnia while there was a subsequent reduction in the posthypercapnic period. These data suggest that an important mechanism of acid-base regulation during hypercapnic acidosis is modification of the chloride cell-associated Cl-/HCO3- exchange mechanism. We suggest that bullheads vary availability, and thus functional activity, of this transporter via reversible morphological alterations of the gill epithelium. The increase in density of PVC microvilli may be associated with sodium uptake and/or acidic equivalent excretion during acidosis. PMID- 1628311 TI - Influence of N-linked oligosaccharides on the processing and neurite-promoting activity of proteoglycans released by neurons in vitro. AB - Inhibitors of enzymes involved in processing of N-linked oligosaccharides were used to examine biosynthesis and the neurite-promoting activity of proteoglycans produced by and released from dissociated chick embryo spinal cord neurons in vitro. In the cell compartment and in conditioned medium both castanospermine and swainsonine inhibited 3H-glucosamine incorporation into glycoprotein but only castanospermine reduced 3H-glucosamine incorporation into heparan sulphate and chondroitin sulphate proteoglycans. All of the neurite-promoting activity of neuron-conditioned medium that complexed to laminin was associated with heparan sulphate proteoglycans as determined by heparitinase digestion. Neuron conditioned medium prepared in the presence of castanospermine displayed a 38 +/- 6% (mean +/- SD) reduction in 3H-glucosamine incorporation into heparan sulphate proteoglycans and a 30 +/- 5% reduction in substrate-attached neurite-promoting activity compared to control conditioned medium and to conditioned medium prepared in the presence of swainsonine. When neurons were coincubated with castanospermine, neurite growth on a laminin substrate was 50 +/- 10% of control growth or growth in the presence of swainsonine. However, when neuron-conditioned medium was used to pretreat the laminin substrate the inhibitory effect on neurite growth produced by castanospermine coincubation was reversed. Influences on neuronal processing of N-linked oligosaccharides alter neurite growth directly and also alter the neurite-promoting activity of neuron-conditioned medium by inhibiting the synthesis of heparan sulphate proteoglycans. These studies provide further evidence for an autocrine role for heparan sulphate proteoglycans in neurite growth. PMID- 1628312 TI - Functional morphology of the neuroendocrine sodium influx-stimulating peptide system of the pond snail, Lymnaea stagnalis, studied by in situ hybridization and immunocytochemistry. AB - The functional morphology of the neuroendocrine system producing sodium influx stimulating (SIS) peptide in the pond snail, Lymnaea stagnalis, was studied by in situ hybridization and immunocytochemistry. The SIS-peptide, which is 76 amino acids long, stimulates sodium uptake from the ambient medium. Two synthetic DNA probes were used for in situ hybridization. The nucleotide sequences were chosen from the cDNA structure; they encode amino acids 8-17 and 64-73, respectively. SIS-peptide sequences 10-20 and 67-76 were synthesized and antibodies were raised to them and affinity-purified. In addition to these antibodies, a monoclonal antibody raised to a bioactive, high-pressure liquid chromatography (HPLC) purified brain extract was used for immunocytochemistry. Paraffin sections of central nervous systems and of whole snails were studied. The SIS-peptide system could be identified as the previously described yellow cell (YC) system by comparing alternate sections treated with the DNA probes, stained with the antibodies, or stained with alcian blue-alcian yellow. SIS-peptide neurons (approximately 45) occur in the ganglia of the visceral ring and in the proximal parts of visceral nerves. Axons run in the nerves of these and in several nerves of other ganglia. Numerous axon branches penetrate the perineurium forming a vast central neurohemal area. The SIS-peptide system innervates the pericardium, the nephridial gland, the reno-pericardial canal, the ureter, the spermoviduct and gonadal acini, the anterior aorta, the ventral buccal artery, and the penis protractor muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628313 TI - Non-granulated peripolar cells exist in the rat glomerulus. AB - The peripolar cell is a unique cell type in the mammalian glomerulus. Peripolar cells are said to be identifiable during light microscopy by their cytoplasmic granules and by their position at the vascular pole; and during scanning electron microscopy by their distinctive surface morphology. We used both techniques to count peripolar cells in 6 normal rat kidneys. Scanning microscopy revealed that 55(+/- 5)% of glomeruli contained at least one peripolar cell whereas light microscopy revealed granulated peripolar cells in only 4(+/- 2)% of glomeruli. Vascular poles which contained peripolar cells previously identified by scanning were then examined by light and by transmission electron microscopy. Serial sections through these peripolar cells demonstrated the absence of cytoplasmic granules. Our observations suggest that the majority of peripolar cells in the rat contain no granules. PMID- 1628314 TI - Mast cell types in the lymph nodes of the opossum Didelphis albiventris (Marsupialia, Didelphidae). AB - Using histological and histochemical techniques, we have found a unique population of mast cells in the lymphatic sinuses of lymph nodes from different anatomical regions of the opossum. The lymphatic-sinus mast cells of the medullary sinuses were numerous, and could be easily distinguished from the connective-tissue mast cells of the dermis and lymph node capsule by their larger size and their enlarged cytoplasmic granules that were also more heterogeneous in shape and staining properties. PMID- 1628315 TI - Local regulation of Leydig cell function by inhibitors of steroidogenic activity. AB - In the testis, local regulation of Leydig cell activity by paracrine factors can modify the response to LH. The identity of factors within paracrine actions has required the use of in vitro Leydig cell bioassay procedures, yet it has only recently been demonstrated that steroidogenic activity can be maintained in culture. There is renewed interest in the detection of both steroidogenic stimulatory and inhibitory activities using these systems, but this review presents the case for a role of inhibitory factors in the local regulation of Leydig cell function. PMID- 1628316 TI - A cell surface antigen associated with meiosis in male Staurdoderus scalaris (Orthopteran). AB - Immunofluorescence has identified seven monoclonal antibodies reactive with the surface of meiotic cells and absent in premeiotic cells. Analysis by immunogold electron microscopy indicated that these antigens were present on the external surface of the cells and were coincident with the presence of synaptonemal complexes in the nucleus. On immunoblots a common glycosylated protein of 205 kDa was recognized, in addition to smaller subunits, suggesting the presence of a protein complex comprised of smaller peptides. PMID- 1628317 TI - Influence of low density lipoproteins on vascular smooth muscle cell growth and motility: modulation by extracellular matrix. AB - Low density lipoproteins (LDL) are thought to play a major role in cardiovascular diseases such as atherosclerosis. Much remains to be done to understand the cellular effects of LDL and how the extracellular matrix (ECM) influences these effects. We found that LDL produced a dose dependent increase in vascular smooth muscle cell (SMC) proliferation. The ECM altered the proliferative response of SMC to LDL: on collagen I there was a 66% inhibition, endothelial cell derived ECM a 2-fold increase, and collagen IV no difference in proliferation compared to paired controls. LDL affected SMC motility (cell area and shape factor) but the extent and direction of the effect depended on whether the cells were cultured on uncoated or coated dishes. LDL treated cultures had a 5-fold lower migration rate but net movement was not different, suggesting that LDL decreased SMC random movement. There was a dose-dependent accumulation of lipid by SMC incubated with LDL and, subsequently, cytoplasmic lipid droplets were observed. Cells cultured on uncoated plates showed an increased cholesterol content as a function of LDL concentration. In contrast, cells cultured on a collagen IV matrix showed no net change in cholesterol content over the range of LDL concentrations studied. Hence, the uptake of LDL cholesterol appears to be completely inhibited by this matrix. These studies indicate that the influence of LDL on several SMC parameters is modulated by ECM components. PMID- 1628318 TI - Changes in tropomyosin during primary culture of embryonic myocardiocytes. AB - We chose the Hamburger and Hamilton's stage 29 (HH 29) to investigate the expression of tropomyosin in chick myocardiocytes during 14 days on culture. Throughout 14 days of cell culture, changes in cell morphology were accompanied by a redistribution of tropomyosin in different cell compartments. We used FACScan, SDS-PAGE and densitometric analysis to quantify total cell tropomyosin and concentrations of this protein in different cell fractions. Tropomyosin was found mostly in the cytoskeletal fraction than in the cytoplasmic. When we compared the densitometric values from SDS-PAGE of cells in different stages of development we found that in HH 19, tropomyosin was more abundant in the cytoplasmic than in the cytoskeletal fraction. By HH 29, the two fractions had become inverted, and in HH 39, tropomyosin was clearly more abundant in the cytoskeletal than in the cytoplasmic fraction. In the IFI analysis, tropomyosin was found to label the Stress fiber-like structures (SFL) in different patterns depending on the area of the cell which expressed this protein. PMID- 1628319 TI - High molecular weight microtubule-associated proteins within testes of hemipteran insects. AB - Results presented here indicate that the high molecular weight microtubule associated proteins isolated from the ovaries of the hemipterans, Oncopeltus fasciatus and Notonecta glauca, while absent from nervous tissue, are present in the testes of the respective species. Here they are seen to be located to extensive microtubule aggregates within the cells surrounding the sperm, but not obviously to the sperm themselves. PMID- 1628320 TI - Localization of chromatin in "persistent" nucleoli in okadaic acid treated HeLa cells. AB - In okadaic acid treated HeLa cells, the chromosomes sometimes condense without being accompanied by nuclear envelope breakdown. These cells show "persistent" nucleoli. Within these "persistent" nucleoli the intranucleolar chromatin condenses and can be observed in the region of the dense nucleolar component (DNC) of the nucleoli. Other nucleolar components, namely the fibrillar centre (FC) and the granular component (GC) remain unchanged. These observations strongly speak for the localization of nucleolar chromatin (ribosomal cistrons) within the dense nucleolar component of the interphase nucleolus. PMID- 1628321 TI - The interaction of Staphylococcal protein A with free coelomocytes of annelids. AB - The Staphylococcal protein A (SpA) binding protein was detected on the surface of annelid coelomocytes. The flow cytometric analysis revealed that 50% coelomocytes of Lumbricus terrestris react with SpA, a figure six times higher than the number of positive coelomocytes found in Eisenia foetida. PMID- 1628322 TI - Homologous antigen for T cell receptor in axial organ cells from the asterid Asterias rubens. AB - The axial organ (A.O. cells) of the sea star Asterias rubens is a primitive immune organ. The total population was fractionated into two populations: adherent (B-like) and non-adherent (T-like) to nylon wool. The adherent cells resemble mammalian B lymphocytes and bear homologous human T cell receptor (beta chain) to a higher degree than T-like cells which resemble T lymphocytes. PMID- 1628323 TI - Association of glycosphingolipids with intermediate filaments of mesenchymal, epithelial, glial, and muscle cells. AB - We reported recently that two glycosphingolipids (GSLs), globoside (Gb4) and ganglioside GM3, colocalized with vimentin intermediate filaments of human umbilical vein endothelial cells. To determine whether this association is unique to endothelial cells or to vimentin, we analyzed a variety of cell types. Double label immunofluorescent staining of fixed, permeabilized cells, with and without colcemid treatment, was performed with antibodies against glycolipids and intermediate filaments. Globoside colocalized with vimentin in human and mouse fibroblasts, with desmin in smooth muscle cells, with keratin in keratinocytes and hepatoma cells, and with glial fibrillary acidic protein (GFAP) in glial cells. Globoside colocalization was detected only with vimentin in MDCK and HeLa cells, which contain separate vimentin and keratin networks. GM3 ganglioside also colocalized with vimentin in human fibroblasts. Association of other GSLs with intermediate filaments was not detected by immunofluorescence, but all cell GSLs were detected in cytoskeletal fractions of metabolically labelled endothelial cells. These observations indicate that globoside colocalizes with vimentin, desmin, kertain and GFAP, with a preference for vimentin in cells that contain both vimentin and keratin networks. The nature of the association is not yet known. Globoside and GM3 may be present in vesicles associated with intermediate filaments (IF), or bound directly to IF or IF associated proteins. The prevalence of this association suggests that colocalization of globoside with the intermediate filament network has functional significance. We are investigating the possibility that intermediate filaments participate in the intracellular transport and sorting of glycosphingolipids. PMID- 1628324 TI - Colchicine-binding sites of brain tubulins from an antarctic fish and from a mammal are functionally similar, but not identical: implications for microtubule assembly at low temperature. AB - The tubulins of Antarctic fishes possess adaptations that favor microtubule formation at low body temperatures (Detrich et al.: Biochemistry 28:10085-10093, 1989). To determine whether some of these adaptations may be present in a domain of tubulin that participates directly or indirectly in lateral contact between microtubule protofilaments, we have examined the energetics of the binding of colchicine, a drug thought to bind to such a site, to pure brain tubulins from an Antarctic fish (Notothenia gibberifrons) and from a mammal (the cow, Bos taurus). At temperatures between 0 and 20 degrees C, the affinity constants for colchicine binding to the fish tubulin were slightly smaller (1.5-2.6-fold) than those for bovine tubulin. van't Hoff analysis showed that the standard enthalpy changes for colchicine binding to the two tubulins were comparable (delta H degrees = +10.6 and +7.4 kcal mol-1 for piscine and bovine tubulins, respectively), as were the standard entropy changes (delta S degrees = +61.3 eu for N. gibberifrons tubulin, +51.2 eu for bovine tubulin). At saturating concentrations of the ligand, the maximal binding stoichiometry for each tubulin was approximately 1 mol colchicine/mol tubulin dimer. The data indicate that the colchicine-binding sites of the two tubulins are similar, but probably not identical, in structure. The apparent absence of major structural modifications at the colchicine site suggests that this region of tubulin is not involved in functional adaptation for low-temperature polymerization. Rather, the colchicine site of tubulin may have been conserved evolutionarily to serve in vivo as a receptor for endogenous molecules (i.e., "colchicine-like" molecules or MAPs) that regulate microtubule assembly. PMID- 1628325 TI - Human cardiac and skeletal muscle spectrins: differential expression and localization. AB - We describe multiple human cardiac and skeletal muscle spectrin isoforms. Cardiac muscle expresses five erythroid alpha,beta spectrin-reactive isoforms with estimated MR's of 280, 274, 270, 255, and 246 kD, respectively. At least one nonerythroid alpha-spectrin of MR 284 kD is expressed in heart. While skeletal muscle shares the 280, 270, and 246 kD erythroid spectrins, it expresses an immunologically distinct 284 kD nonerythroid alpha-spectrin isoform. The 255 kD erythroid beta-spectrin isoform is specific for cardiac tissue. By immunocytochemistry, both erythroid beta- and nonerythroid alpha-spectrins are localized to costameres, the plasma membrane, and the neuromuscular junctional region. PMID- 1628326 TI - Different assembly properties of cod, bovine, and rat brain microtubules. AB - Assembly properties of cod, bovine, and rat brain microtubules were compared. Estramustine phosphate, heparin, poly-L-aspartic acid, as well as NaCl, inhibited the assembly and disassembled both bovine and rat microtubules by inhibition of the binding between tubulin and MAPs. The assembly of cod brain microtubules was in contrast only marginally affected by these agents, in spite of a release of the MAPs. The results suggest that cod tubulin has a high intrinsic ability to assemble. This was confirmed by studies on phosphocellulose-purified cod tubulin, since the critical concentration for assembly was independent of the presence or absence of MAPs. The results show therefore that cod brain tubulin has, in contrast to bovine and rat brain tubulins, a high propensity to assembly under conditions which normally require the presence of MAPs. Even if cod MAPs, which have an unusual protein composition, were not needed for the assembly of cod microtubules, they were able to induce assembly of bovine brain tubulin. Both cod and bovine MAPs bound to cod microtubules, and bovine MAP1 and MAP2 bound to, and substituted at least the 400 kDa cod protein. This suggests that the tubulin binding sites and the assembly-stimulatory ability of MAPs are common properties of MAPs from different species, independent of the tubulin assembly propensity. PMID- 1628327 TI - Differential sorting of beta tubulin isotypes into colchicine-stable microtubules during neuronal and muscle differentiation of embryonal carcinoma cells. AB - Pluripotent P19 embryonal carcinoma (EC) cells were differentiated along the neuronal and muscle pathways. Comparisons of class I, II, III, and IV beta tubulin isotypes in total and colchicine-stable microtubule (MT) arrays from uncommitted EC, neuronal, and muscle cells were made by immunoblotting and by indirect immunofluorescence microscopy. In undifferentiated EC cells the relative amounts of these four isotypes are the same in both the total and stable MT populations. Subcellular sorting of beta tubulin isotypes was demonstrated in both neuronal and muscle differentiated cells. During neuronal differentiation, class II beta tubulin is preferentially incorporated into the colchicine-stable MTs while class III beta tubulin is preferentially found in the colchicine-labile MTs. The subcellular sorting of class II into stable MTs correlates with the increased staining of MAP 1B, and with the expression of MAP 2C and tau. Although muscle differentiated cells express class II beta tubulin, stable MTs in these cells do not preferentially incorporate this isotype but instead show increased incorporation of class IV beta tubulin. Muscle cells do not show high levels of MAP 1B and do not express MAP 2C or tau. These results are consistent with the hypothesis that a subcellular sorting of tubulin isotypes is the result of a complex interaction between tubulin isotypes and MT-associated proteins. PMID- 1628328 TI - [Monitoring the effects of oxyphilline Spofa in the umbilical-placental circulation]. AB - Vasodilatation treatment is an inevitable part of comprehensive therapy of intrauterine growth retardation of the foetus. The authors present the results of investigations of the effect of Oxyphylline on the umbilical and placental circulation of pregnant women with confirmed disorders of the flow parameters. Oxyphylline Spofa, 3 x 100 mg orally, is the drug of choice in treatment of foetal hypotrophy with a marked effect on the umbilical and placental circulation. PMID- 1628329 TI - [Treatment of toxoplasmosis in pregnant women]. PMID- 1628330 TI - [Delivery of neonates with a birth weight of less than 1500 grams. Perinatal results during a 6-year period and possibilities of affecting them]. AB - The authors evaluated the perinatal mortality and condition on delivery of 167 neonates with a birth weight under 1500 g who were delivered and hospitalized at the 2nd Department of Gynecology and Obstetrics in Brno between Jan. 1, 1985 and Dec. 31, 1990. The perinatal mortality of neonates with a birth weight below 1000 g was 73.1%, of those with a birth weight 1000 g-1500 g it was 25.9%. Early neonatal mortality was not influenced by the patient's age exceeding 30 years, occupation, environment, status, number of interrupted pregnancies, spontaneous abortions and previous spontaneous and induced deliveries, administration of tocolysis, corticoids, the position of the foetus, transport in utero, way of delivery, indication for Caesarean section and sex. Early neonatal mortality was influenced by the mother's age less than 20 years, administration of antibiotics, multiple pregnancy, grade of asphyxia, presence of RDS, necessity of respiratory support, incidence of intracerebral haemorrhage and birth trauma. In the discussion the authors mention possible ways of reducing the perinatal morbidity and early neonatal morbidity in the mentioned range of birth weights. PMID- 1628331 TI - [Use of photoplethysmography in the diagnosis of venous disorders in pregnancy]. PMID- 1628332 TI - [Personal experience with Scheerer's emergency cerclage]. PMID- 1628334 TI - [Reliability of the CandidaSure Test in the diagnosis of mycotic vaginal inflammations]. PMID- 1628333 TI - [Morbidity after induced abortions in 1989]. PMID- 1628335 TI - [Ovulation of insufficiently developed follicles]. PMID- 1628336 TI - [Acardius acephalus as a complication in labor]. PMID- 1628337 TI - [DNA flow cytometry: perspective prognostic parameters in carcinoma of the uterine cervix]. AB - We studied the relation between the 5-year disease free interval and the flow cytometric DNA content in a group of 55 patients treated by radiation for squamous cell carcinoma of the uterine cervix, stages Ib-IIIb (FIGO). The diploid DNA content was associated with a better prognosis, while prognostically unfavourable tumours tended to be aneuploid. The relation was statistically significant in the whole group (p = 0.016), in stage II disease (p = 0.003) and in the subgroup formed by the combination of stages I and II (p = 0.000). In stage III we did not prove the relation. Analysis of the survival function revealed also a better prognosis of diploid tumours (p = 0.041) in the whole group. The division into clearly diploid and non-diploid tumours seems to be more suitable for evaluation (p = 0.012). The difference between the prognostically favourable and unfavourable groups is expressed more clearly. We consider the flow cytometric DNA content a perspective prognostic parameter in squamous cell carcinoma of the uterine cervix. Its significance is apparent especially in patients treated by radiotherapy, because the size of the tumour cannot be assessed reliably in these cases. PMID- 1628338 TI - [Prostaglandins and management of labor after prior cesarean section]. PMID- 1628339 TI - [Comparison of methods of treatment in mycotic vulvovaginitis]. PMID- 1628340 TI - [Intraperitoneal administration of noxythiolin VUFB in the prevention and therapy of inflammatory postoperative complications in gynecology]. PMID- 1628341 TI - [Intrauterine insemination using cryopreserved donor sperm, a methods which increases therapeutic success]. PMID- 1628343 TI - [The aggressive patient in the physician's office]. PMID- 1628342 TI - [Continuing professional education, recertification and subspecialization]. PMID- 1628344 TI - [A computer expert system for malignant lymphoma]. AB - Structure of a data base for histo-oncological diagnosis of malignant lymphomas by expert system Fel-Expert 2.9 is introduced. The data base has a 110,000 byte range and an average consultation with user's high diagnostic certainty lasts 2-3 minutes and comprises 20-25 inquiries. Possible acceleration of consultation process is discussed. PMID- 1628346 TI - [Relapsing polychondritis--ultrastructure in 2 additional cases]. AB - A 37-year-old woman and a 74-year-old man with typical clinical history of relapsing polychondritis enabled electron microscopical analysis of various cartilages (ear, nasal septum, rib). Apoptotic lesion and degradation of chondrocytes combined not always with changes of their lacunae prevailed in both patients, fragmentation of elastic tissue in the man. Lesions of chondrocytes, a bit varied and asynchronous in intensity were observed as everywhere in a single cartilage as in cartilages from different sites. PMID- 1628347 TI - [Professor Pavel Kucera--the first head of the University Institute of Pathologic Anatomy in Brno]. AB - Pathologist Dr. Pavel Kucera was one of the first professors of the Medical Faculty of Masaryk University in Brno. History of his uncommon life was described in detail. Some mistakes occurring in literature were corrected according to data from Kucera's personal file in the Archives of the Masaryk University. PMID- 1628345 TI - [Liver cholestasis in neonates and young children]. AB - Liver cholestasis was found in 50 autopsies (23 per cent) among 221 neonates and infants who died in intensive care units. It developed from the 4th postnatal day, was mostly mild and present in biliary capillaries as well as in small interlobular biliary ducts, later there was found phagocytosis of biliary pigment by Kupffer cells. In protracted jaundice there was an irregular increase of small cholangioles derivable from a ductal transformation of periportal hepatocytes. Bile ducts proliferation was connected with a slight widening of portal tracts in infants surviving until the 6th and 8th week. The cause of cholestatic liver lesion remained obscure. PMID- 1628348 TI - [Malignant lymphomas of the mantle zone]. AB - A series of mantle zone malignant lymphomas rendered ideas about their common features. Patients of higher age prevailed, prognosis was favourable even up to a steady state. Small cell blastic (centrocytoid) malignant lymphoma of the mantle zone (in lymphnodes, spleen, skin, parotid gland) tended to produce lymphoepithelial lesions, angioinvasion, and especially to spread into sinuses which did not influence prognosis in a positive way. B monocytoid medium cell malignant lymphoma (in lymphnodes, stomach, skin) was closer to classic malignant lymphomas in its behaviour but varied localization and usual mixed cytology produced rather controversial pictures. Independence of further variants (plasmacytoid, clear celled) was doubtful. Nevertheless, to be familiar with them was useful for their identification in mixed cytology variants which were very frequent. Relation of clear cell lymphomas to hairy cell leukaemias and independence of so called paracortex mixed malignant lymphoma as well as reticulohistiocytic malignant lymphoma was discussed. PMID- 1628349 TI - [Primary MALT-type malignant lymphomas of the salivary glands]. AB - Six cases of primary extranodal lymphomas in big salivary glands, which met criteria of MALT lymphoma, were investigated with the aid of antibodies against Ig, light chains, LCA and EMA, in addition in two cases against Ig heavy chains and with antibodies KL-1 and VCHL-1. All the tumours had centrocytoid morphological features, one of them showed signs of focal blastic transformation into centrocytoid centroblastoma. Tumour cells showed twice plasmacytic and three times plasmacytoid differentiation with intracytoplasmic Ig monoclonality (once IgM/kappa, once IgA/kappa, three times kappa positivity). They were positive in reaction against epimyoepithelial proliferation. A picture of myoepithelial sialoadenitis with partial lymphomatous infiltration prevailed in two cases and a lymphoma picture with remnants of sialoadenitis in three cases. Features of inflammatory process were lacking in a case with blastic transformation. There is a dispute whether features of sialoadenitis belong to the defining criteria of MALT type lymphoma or can disappear during blastic transformation of a low grade malignant lymphoma. PMID- 1628350 TI - [Prognostic relevance of histopathologic subtyping of mixed-cell Hodgkin's disease]. AB - Mixed cellular (MC) type of Hodgkin disease was studied in a group of 92 bioptic cases diagnosed before the start of treatment. A precise histological analysis showed one subtype with lower malignancy (MC 1) and a second one with higher malignancy (MC 2). Subtype MC 1 comprised 61 cases (66 per cent), subtype MC 2 31 cases (34 per cent). Histomorphological subtyping was brought into correlation with clinical data of survival available in 65 cases (44 cases of subtype MC 1,21 cases of subtype MC 2). Different survival in both subtypes had statistical significance and prognostic relevance. Suggested subtyping is simple, based on common histological slides, without need of special additional investigation. PMID- 1628351 TI - [Interfollicular Hodgkin's disease]. AB - Two cases of so-called interfollicular Hodgkin's disease, one case lacking of all histological criteria and one case of lymphadenitis mimicking Hodgkin's disease, were identified among 76 patients with Hodgkin's disease. Case 1 and 2 rank among lymphocyte predominance type, case 3 showed mixed cellularity. They shared a progressive transformation of germinal centres which was proved by immunohistology. Leu M 1 antibody-positive cells were found in both cases of the so-called interfollicular Hodgkin's disease and not in lymphadenitis mimicking Hodgkin's disease. PMID- 1628352 TI - [The Informatorium by Komenius and modern pediatrics]. AB - The Informatorium "The School of Infancy" by Comenius is probably the first treatise on the development and training of infants and children in the family during the first six years of life. Although this year 360 years will elapse since its first edition, the ideas of this work are of topical interest and are inspiring even today. This applies e.g. to the prenatal development, the relationship between biological maturing and training, the necessity to avoid forceful pedantic control as well as excessive permissiveness, the necessity to supply adequate sensory and emotional stimuli at a very early age, the necessity to support all natural activities of the child while taking care of his safety, maturity and readiness for school, emphasis on fundamental values of life, etc. Comenius proved himself a sensitive psychologist who understood the specificity of thinking and sensations of children, long before developmental psychology was established as a science. PMID- 1628353 TI - [Photoisomers of bilirubin in the blood of neonates during phototherapy]. AB - In a group of mature neonates with hyperbilirubinaemia the authors investigated by chromatography, using the HPLC method, levels of bilirubin photoisomers before phototherapy, in the course of phototherapy and after its termination. The configuration isomer 4 Z, 15 E is detected in blood of all icteric neonates already before the onset of treatment in a mean concentration of 5.2 (s = 3.8) mumol/l, during phototherapy its mean concentration is 23.0 (s = 8.0) mumol/l. Photoisomers participate in non-conjugated bilirubinaemia on average by 10%: 92% are formed by isomer 4 Z, 15 E, 5% by isomer 4 E, 15 Z and 3% by the structural isomer lumirubin. On the day following discontinuation of treatment the mean photoisomer concentrations are significantly lower than during phototherapy and significantly higher than before its initiation. PMID- 1628354 TI - [Screening for alpha 1-antitrypsin deficiency in neonates]. AB - In a two-year investigation 113,274 children were screened for alpha-1 antitrypsin deficiency. An original and cheap method was used. In children with an alpha-1-antitrypsin values lower than 1.5 g/l the phenotype was assessed. In 120 neonates alpha-1-antitrypsin was assessed by screening and also quantitatively. The physiological range of alpha-1-antitrypsin for neonates is: 1.4-3.32 g/l. A low incidence of alpha-1-antitrypsin in the Czechoslovak population, as compared with investigations abroad, was revealed. The authors discuss the possibility to extend screening from the clinical, ethical and economic aspect to the entire republic. PMID- 1628355 TI - [Acoustic frequency analysis of auscultation findings in neonates]. AB - The authors analyzed 280 auscultation findings of 35 neonates with birth weights of 1800-4500 g and 65 pathological neonates with birth weights of 1150-3600 g. For recording of the auscultation findings an electronic phonendoscope EST 40 (Bosch) was used and the finding was recorded on a microtape recorder (Olympus). The frequency analysis was made on a Sonagraf analyzer (Kay Elemetric), using a 45 Hz filter a time range of 2.4 sec. From the results of the work ensues that in physiological neonates two basis types of sonagrams can be detected: 1. the record presenting itself as a continuous zone of noise with maximal cumulation of acoustic energy up to 500 Hz where the ratio of acoustic energy is equal in both stages of the respiratory cycle. The clinical correlate is "alveolar respiration". 2. a record with a discontinuous zone of noise with a more expressive ratio of acoustic energy up to 2500 Hz during inspiration. The clinical correlate is "sharper bronchoalveolar respiration". In the group of pathological neonates with different pneumopathies further sonagraphic phenomena were detected: a) "rales" as discontinuous acoustic phenomena persisting for 7-35 msec with a frequency range up to 3000 Hz, without a harmonious structure, present during inspiration as well as expiration, b) "transmitted phenomena"- discontinuous acoustic phenomena persisting for 75-150 msec with a frequency range up to 6000 Hz, without a harmonious structure, c) "wheezing"--continuous acoustic phenomena with a clearly marked harmonious acoustic structure lasting 540 +/- 240 msec with a frequency of the basic sound of 500 +/- 240 msec.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628356 TI - [Kinetics of gentamycin in premature infants with a low birth weight during the first four days of postnatal life]. AB - The authors investigated in a group of 19 premature neonates with a low birthweight (0.65-2.1 kg) during the first four days of postnatal life the pharmacokinetics of gentamycin after indicated administration of 2 mg/kg of the antibiotic by the i.v. route by a 30-minute infusion in 18-hour intervals. Serum concentrations of gentamycin were assessed by immunoassay 0.5 hours before administration and then 0.5, 5.5, 11.5 and 17.5 hours after the 5th infusion, i.e. in a steady state. The maximum serum concentrations detected 0.5 hours after the completed infusion exceeded 10 mg/l in 21% of the neonates, while the minimal concentrations of the antibiotic before the next administration were above 2 mg/l in 42% of the infants. The calculation of pharmacokinetic parameters according to the one-compartment model revealed considerable interindividual differences of all values. The authors consider particularly important the low clearance value of the antibiotic (30.24 +/- 14.55 ml/kg.hour-1) which may lead to cumulation of gentamycin and its toxic action. Gentamycin administration to premature neonates should be associated with monitoring of serum concentrations of the drug which would make individual adjustment of the dosage possible. PMID- 1628357 TI - [Epavit--a dietary preparation suitable for use in pediatric practice]. PMID- 1628358 TI - [Recombinant erythropoietin--a fundamental change in the treatment of anemia?]. AB - The authors summarize in the submitted review recent findings on erythropoietin (EPO) and recombinant EPO (rHuEPO), a new therapeutic preparation which changed fundamentally the clinical picture of many diseases associated with anaemia. The authors discuss the physiology of EPO, regulation of its secretion, mechanism of action on bone marrow and its importance in the pathogenesis of polycythaemia and in particular anaemia. They emphasize in particular the use of rHuEPO in the treatment of different forms of anaemia. They analyze the pathogenesis of renal anaemia and the importance of treatment with rHuEPO for improvement of the haemogram as well as the general condition of the patients, their adaptability, improved psychic condition and reduced need of transfusions. The authors draw attention to the great importance of treatment with rHuEPO in the treatment of anaemias associated with inflammatory diseases (rheumatoid arthritis, AIDS, Crohn's disease and others), anaemia associated with malignancies, in the treatment of surgical diseases and in autotransfusions, in anaemias of premature infants and in some congenital heart diseases. The introduction of rHuEPO into the treatment of anaemia is a great advance of modern pharmacotherapy, which moreover opened new vistas on the role of anaemia in the clinical picture of many diseases. PMID- 1628359 TI - [Chronic fatigue syndrome]. PMID- 1628360 TI - [What is the risk of future development of ischemic heart disease in juvenile hypertensives?]. AB - The investigation was focused on the incidence of some amenable risk factors of ischaemic heart disease in 51 adolescent men aged 15-19 years. The author compares the incidence of these risk factors in normotonics and hypertonics. The investigation revealed that the group of juvenile hypertonic subjects is from the aspect of future development of ischaemic heart disease at greater risk, as compared with the group of normotonic subjects. In families of juvenile hypertonic subjects the disease is more frequent in parents and grandparents and there are more frequent early deaths from this disease in the family. Juvenile hypertonics are more frequently obese and have a more risky level of serum cholesterol, as compared with adolescent normotonic subjects. The task of the general practitioner for children and adolescents is to detect by early screening and to include in dispensary care all subjects at risk and to recommend appropriate provisions to reduce the risk of development of ischaemic heart disease in adult age. PMID- 1628361 TI - [[The Jindrichuv Hradec model of clinical practice in pediatric pneumology. 1. Organization and screening]. PMID- 1628362 TI - [Mortality in children below 1 year of age in the first half of 1991]. PMID- 1628363 TI - [Summary of knowledge required for levels I-III in postgraduate training in pediatric pneumonology]. PMID- 1628364 TI - Reversal of multidrug resistance by phenothiazines and structurally related compounds. AB - The multidrug-resistance (MDR)-reversal activity of 232 phenothiazines and structurally related compounds was tested in MDR P388 cells. Such activity was found among compounds exhibiting two ring structures (phenyl, cyclopentyl, cyclohexyl, thienyl or 5-norbornen-2-yl but not pyridinyl) linked by a variety of bridge types and possessing a secondary or tertiary amine group. Among 192 such compounds, 31.8% displayed good activity (MDR-reversal ratio, greater than or equal to 10) and 8.3%, outstanding activity (MDR-reversal ratio, greater than or equal to 30). In a subgroup comprising 56 compounds with a carbonyl residue, 4 with sulfuryl residue and 1 with thienyl residue, 42.7% showed good activity and 18%, outstanding activity. The contribution of these residues to the MDR-reversal activity was particularly evident among compounds containing a cyclic tertiary amine. Among 49 such compounds, 51% displayed good activity and 20.4%, outstanding activity, whereas among the 85 compounds lacking such groups, only 31.8% showed good activity and 4.7%, outstanding activity. Enhancement of this activity by the carbonyl group is also obtained when the latter is part of an amide bond of a tertiary amine. As compounds with a carbonyl group located on the rings, on the bridge to the amine group or beyond the amine are efficient MDR reversers, it seems that the exact molecular location of the carbonyl group is not critical for the elicitation of this activity. PMID- 1628365 TI - Antitumor effects of N-alkylated polyamine analogues in human pancreatic adenocarcinoma models. AB - Adenocarcinoma of the pancreas presents a formidable challenge both experimentally and clinically, whereby effective anticancer therapy is lacking. We have recently explored a relatively new class of antitumor agents in pancreatic cancer cell lines and have found the bis-ethyl derivatives of spermine to show considerable promise. In the present paper, we report the results of in vivo studies demonstrating the antitumor activity of two of these N-alkylated analogues, N1,N14-bis(ethyl)homospermine (BEHSPM) and N1,N11 bis(ethyl)norspermine (BENSPM) in athymic (nude) mouse xenografts of two human pancreatic ductal adenocarcinoma cell lines, PANC-1 (poorly differentiated) and BxPC-3 (moderately well-differentiated). BENSPM was found to exert greater antitumor activity in vivo than either BEHSPM or other conventional agents, largely because higher doses could be given due to its lower toxicity to mice. BENSPM shows greater activity than any other agent we have thus far tested against our pancreatic-cancer models. Optimal schedules of administration have yet to be determined. Nevertheless, of the analogues tested, BENSPM presently appears to be the analogue of choice for further development. PMID- 1628367 TI - Dose dependence of the cytokinetic and cytotoxic effects of epirubicin in vitro. AB - CHO cells were exposed in vitro for 1 h to concentrations of 0.1-20 micrograms/ml of the cytostatic drug epirubicin. Population growth, survival fractions, cell cycle-phase distribution, and BrdU incorporation were analyzed. A fraction of the cells showed a transitory cytostatic reaction at 1 microgram/ml, and greater than 99% of the cells were killed at 10 micrograms/ml. The survival curve was biphasic with a steep slope at concentrations of up to 5 micrograms/ml. Approximately 0.1% of the cells were resistant to higher concentrations of epirubicin. Bivariate DNA/BrdU flow cytometry revealed that the sensitive cells were blocked and probably killed in the G2M phase of the cell cycle. PMID- 1628366 TI - Regulatory and antiproliferative effects of N-alkylated polyamine analogues in human and hamster pancreatic adenocarcinoma cell lines. AB - N-Alkylated polyamine analogues have been shown to exert antiproliferative effects in several tumor models, with the bis-ethyl derivatives exerting the greatest suppression of polyamines by virtue of down-regulation of the polyamine biosynthetic enzymes. Pancreatic adenocarcinoma presents a challenge both clinically and experimentally due to its inherent resistance to conventional therapy, which results in its having the worst 5-year survival rate of all cancers. We have previously shown that N1,N12-bis(ethyl)spermine (BESPM) is much more potent than the polyamine enzyme inhibitor alpha-difluoromethylornithine (DFMO) against pancreatic adenocarcinoma cell lines. In the present study, we compared the biochemical and antiproliferative effects of two N-alkylated polyamine analogues, N1,N14-bis(ethyl)homospermine (BEHSPM) and N1,N11 bis(ethyl)norspermine (BENSPM) in two human pancreatic ductal adenocarcinoma cell lines, PANC-1 (poorly differentiated) and BxPC-3 (moderately well differentiated), and in the WD PaCa (well-differentiated ductal) hamster cell line. BENSPM displayed greater antiproliferative activity in the human pancreatic cancer cell lines, whereas BEHSPM was more potent in the hamster cell line. Both BEHSPM and BENSPM suppress the activity of the major biosynthetic enzymes ornithine decarboxylase and S-adenosylmethionine decarboxylase. However, the induction of polyamine depletion in the human cell lines was only modest for BENSPM and minimal for BEHSPM, which suggests that the substantial antiproliferative activity of these analogues may result from mechanisms other than polyamine depletion. The somewhat greater polyamine depletion seen following treatment with BENSPM is thought to result from its striking induction of spermidine/spermine N1-acetyltransferase. The biochemical and antiproliferative activity of BENSPM makes it an attractive agent for further preclinical and clinical development, especially in pancreatic cancer. PMID- 1628368 TI - A high-performance liquid chromatographic assay for CI-973, a new anticancer platinum diamine complex, in human plasma and urine ultrafiltrates. AB - CI-973 is a new platinum compound with antitumor properties that is currently undergoing phase II clinical trials. A high-performance liquid chromatographic (HPLC) assay was developed and validated for ultrafiltrates of human plasma and urine to support phase I clinical trials. Plasma ultrafiltrate (0.5 ml) was extracted using C18 solid-phase cartridges. Urine was diluted 10-fold and extracted first with SAX solid-phase cartridges and then with C18 cartridges. For both matrices, the eluate from the C18 cartridges was injected directly. A Whatman PAC 10 column (4.6 x 250 mm, 10-microns particle size) and ultraviolet detection at 205 nm were used for both analyses. The mobile-phase buffer was 0.05 M sodium perchlorate (pH 2.3). The mobile-phase acetonitrile:buffer ratio, column temperature, and flow rate were 89:11 (v/v), 40 degrees C, and 2.0 ml/min, respectively, for the plasma ultrafiltrate assay and 85:15 (v/v), 50 degrees C, and 1.0 ml/min, respectively, for the urine ultrafiltrate assay. Standard curves were linear from 0.25 to 500 micrograms/ml and from 1.0 to 250 micrograms/ml for the plasma and urine assays, respectively. The accuracy of the assay lay within 4.5% of the nominal values, and the precision was 6.2%; the recovery of CI-973 varied from 79.2% to 105%. CI-973 remains stable in plasma for at least 6 h, at room temperature, in ultrafiltrates of both matrices for at least 15 days at -72 degrees C, and in water for at least 6 months at -72 degrees C. PMID- 1628369 TI - Pharmacokinetics and metabolism of cyclophosphamide in paediatric patients. AB - The pharmacokinetics and metabolism of cyclophosphamide were studied in nine paediatric patients. Plasma samples were obtained from eight subjects and urine was collected from six children during a 24-h period after drug administration. Cyclophosphamide and its major metabolites phosphoramide mustard (PM), carboxyphosphamide (CX), dechloroethylcyclophosphamide (DCCP) and 4 ketocyclophosphamide (KETO) were determined in plasma and urine using high performance thin-layer chromatography-photographic densitometry (HPTLC-PD). Cyclophosphamide (CP) was nearly, if not completely, cleared from plasma by 24 h after its administration. The plasma half-life of CP ranged from 2.15 to 8.15 h; it decreased following higher doses and was shorter than that previously reported for adult patients. Both the apparent volume of distribution (0.49 +/- 1.4 l/kg) and the total body clearance (2.14 +/- 1.4 l m-2 h-1) increased with increasing dose. Renal clearance ranged between 0.12 and 0.58 l/h (mean, 0.43 +/- 0.19 l/h). Between 5.4% and 86.1% of the total delivered dose was recovered as unchanged drug in the urine. The major metabolites identified in plasma and urine were PM and CX. One patient appeared to be deficient in CX formation. This study suggests that there is interpatient variability in the pharmacokinetics and metabolism of CP in paediatric patients. The shorter half-life and higher clearance as compared with adult values indicate faster CP metabolism in children. PMID- 1628370 TI - Doxorubicin and doxorubicinol plasma concentrations and excretion in parotid saliva. AB - The pharmacokinetics of doxorubicin (DOX) and doxorubicinol (DOXol) was studied in six patients with various advanced neoplastic diseases who received 28-72 mg/m2 DOX (nine courses). Plasma and parotid saliva were collected over a 48-h period, and DOX and DOXol were quantified by high-performance liquid chromatography with fluorescence detection. As reported previously, a wide range of plasma levels were found among our patients. It appears that in addition to being quickly cleared from the plasma, both DOX and DOXol are excreted in detectable amounts in parotid saliva, a route of elimination that has been given little attention, if any. Excretion in the saliva exposes the mucosa of the upper gastrointestinal tract to drug and may play a role in causing stomatitis in patients receiving DOX by the i.v. route. Since huge interindividual and pronounced intraindividual differences were found in S/P ratios that mostly were not systematically related to the plasma drug concentration, the concentration in parotid saliva was not useful in predicting the level of free DOX and DOXol in plasma. For the parent drug and its metabolite, the S/P ratios increased significantly with time during the 48-h period after dosing. PMID- 1628371 TI - Pharmacokinetics and tumor concentration of intraarterial and intravenous cisplatin in patients with head and neck squamous cancer. AB - Tumor-tissue platinum levels and major pharmacokinetic parameters were determined in 11 patients with head and neck squamous cancer (HNSC) who were given cisplatin (50 mg/m2 daily x 2 days) and 5-fluorouracil (5-FU; 1000 mg/m2, continuous infusion x 5 days) either i.a. or i.v. The plasma peak platinum concentrations (cmax) and the areas under the curve for total platinum concentration versus time (AUC) during i.a. infusions were lower than the i.v. cmax (mean, 1.92 +/- 0.28 and 4.08 +/- 2.80 mg/l, for i.a. and i.v. infusions, respectively) and AUC values (mean, 22.55 +/- 4.96 and 40.66 +/- 10.71 mg h-1 l-1 for i.a. and i.v. treatment, respectively), suggesting a first-passage extraction of the drug by the tumor mass during i.a. infusion. However, no statistically significant difference was found in platinum tumor concentrations after i.a. administration versus i.v. infusion. The lack of a difference in tumor platinum concentrations between the i.a. and the i.v. administration routes might be explained either by a relatively high blood supply to the tumor area, enabling efflux of the surplus free platinum from the tissue, or by the delay between drug infusion and biopsy. After three cycles of i.a. treatment good tumor remission was obtained with minimal local toxicity. Larger clinical studies testing the advantages of the i.a. administration route over i.v. infusion appear to be necessary. PMID- 1628372 TI - Phase I study of Datelliptium chloride, hydrochloride given by 24-h continuous intravenous infusion. AB - Datelliptium chloride, hydrochloride (SR 95 156B, NSC 626718X, DHE) was studied in a phase I trial of escalating doses given on a single 24-h continuous intravenous infusion schedule. Doses were escalated from 40 to 500 mg/m2 in 19 patients who received a total of 24 courses. Courses were repeated after a minimal interval of 3 weeks. Local venous toxicity occurred at low doses (less than or equal to 100 mg/m2) and was circumvented by the use of a central venous access for higher doses. Other clinical adverse events occurred (greater than or equal to 330 mg/m2), including moderate nausea and vomiting, mild diarrhea, dry mouth, neuropsychiatric manifestations, and fatigue. All of these side effects were reversible and none was dose-limiting. The dose-limiting toxicity was related to hepatic laboratory-test abnormalities in the form of reversible elevations of levels of serum bilirubin and liver enzymes at doses of greater than or equal to 330 mg/m2. The maximum tolerated dose for this schedule is 500 mg/m2. Hematologic toxicity was minimal and non-dose-limiting. Neither drug related deaths nor objective complete or partial responses were observed. However, a minor response and a long-term disease stabilization were obtained. PMID- 1628374 TI - Simultaneous occurrence of acute myelogenous leukemia and seminoma of the testis. AB - Simultaneous tumors are rarely encountered during the course of acute leukemias. We report on a case of seminoma of the testis that occurred during the evolution of acute myelogenous leukemia. To our knowledge, this simultaneous association has not previously been described, but a causal relationship was not apparent in the present case. The likelihood of a common carcinogenesis existed, but direct exposure to carcinogens could not be established. Although the results of a physical examination and echography were normal at the time of diagnosis, we cannot exclude the presence of microscopic cancer of the testis. Since the dissemination pattern of seminoma is usually slower than that observed in this case and the disease remains limited to the lymph nodes for long periods following dissemination, the rapid development of the present case might have been attributable to the immunosuppression and the scrotal sepsis that occurred during the induction therapy. Immunosuppression might have stimulated the progression of a primary microscopic seminoma and the development of metastasis, whereas the scrotal sepsis and inflammation might have favored the occurrence of metastasis through bypass of the lymphatic barrier. PMID- 1628373 TI - Methylprednisolone as antiemetic treatment in breast-cancer patients receiving cyclophosphamide, methotrexate, and 5-fluorouracil: a prospective, crossover, randomized blind study comparing two different dose schedules. AB - The antiemetic response and side effects resulting from treatment with methylprednisolone (MPA) given on two different dose schedules were evaluated in 20 women with breast cancer who were undergoing chemotherapy consisting of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). This randomized, crossover, double-blind study compared the antiemetic efficacy of a single dose of 125 mg MPN with that of two such doses. The study demonstrated the superiority of the latter protocol in preventing CMF-induced nausea and vomiting. The rate of antiemetic response to single vs double doses was as to follows: complete protection, 17% vs 30%; partial and minimal protection, 39% vs 55%; and no protection, 44% vs 15% of the courses, respectively (P = 0.0087). No difference in the antiemetic response rate was found between the first and the second course. Treatment with MPN was well tolerated, and no difference in the incidence of side effects was found between the single-dose and the double-dose schedule. We recommend the use of two doses of 125 mg MPN as prophylactic antiemetic treatment in breast-cancer patients receiving CMF chemotherapy. PMID- 1628375 TI - Comparison of cyclosporin A and SDZ PSC833 as multidrug-resistance modulators in a daunorubicin-resistant Ehrlich ascites tumor. AB - Recent studies by Boesch et al. have demonstrated that a nonimmunosuppressive cyclosporin analog, SDZ PSC 833 (an analog of cyclosporin D), is an active multidrug-resistance modifier that is at least 10 times more potent than cyclosporin A. In vitro accumulation and cytotoxicity experiments using daunorubicin (DNR) and vincristine (VCR) under the influence of SDZ PSC 833 and cyclosporin A were performed in wild-type (EHR2) and the corresponding highly DNR resistant (about 80-fold) Ehrlich ascites tumor cells (EHR2/DNR+). In accumulation experiments, both SDZ PSC 833 and cyclosporin A were found to reverse the multidrug-resistant (MDR) phenotype, but to the same degree at equimolar concentrations. Thus, in EHR2/DNR+ cells, both cyclosporins at 5 micrograms/ml enhanced DNR and VCR accumulation to sensitive levels, but only a negligible effect on DNR accumulation in the drug-sensitive cells was seen. In the clonogenic assay, the cytotoxicity of the two modulators was equal. The lethal dose for 50% of the cell population (LD50) was approx. 7 micrograms/ml for both compounds, and no toxicity was observed at concentrations below 2 micrograms/ml. At nontoxic doses, both cyclosporins effectively increased the cytotoxicity of DNR and VCR in a concentration-dependent manner. The dose response curves were nearly identical and did not demonstrate differences in modulator potency. These data permit the conclusion that cyclosporin A and SDZ PSC 833 do raise the intracellular accumulation of DNR and VCR to the same levels and that SDZ PSC 833 does not potentiate cytotoxicity better than cyclosporin A in EHR2/DNR+ cells. However, since the new compound is nonimmunosuppressive and causes less organ toxicity, clinical studies of its MDR modulating effect seem highly relevant. PMID- 1628376 TI - Salvage therapy for non-Hodgkin's lymphoma with a combination of dexamethasone, etoposide, ifosfamide, and cisplatin. AB - A total of 30 consecutive patients with refractory or relapsing non-Hodgkin's lymphoma (NHL) were treated with a combination of dexamethasone, etoposide (VP 16), ifosfamide, and cisplatin (DVIP). In all, 9 subjects (30%) showed a partial response and 10 (33%) achieved a complete response (CR) lasting from 2.5 to 24+ months. Aggressive histology, no prior therapy with VP-16, a CR to previous chemotherapy, and a treatment-free interval of greater than 6 months prior to the present study were associated with the high CR rate. DVIP caused pronounced myelosuppression (median granulocyte nadir and median platelet nadir, 380/mm3 and 73.000/mm3, respectively), but no drug-related death occurred. We conclude that DVIP is an effective salvage combination, especially in aggressive NHL, that produces acceptable toxicity. PMID- 1628377 TI - A phase II study of sulofenur, a novel sulfonylurea, in recurrent epithelial ovarian cancer. AB - A total of 16 patients with recurrent epithelial ovarian cancer were treated with sulofenur (LY 186641), a novel oral sulfonylurea. All subjects had received previous chemotherapy. Anaemia occurred in all 16 patients, 14 of whom required a blood transfusion, and 2/16 patients received methylene blue for breathlessness due to methaemaglobinaemia. Treatment was discontinued in 2/16 cases due to rising liver enzyme values, which reverted to normal on cessation of the drug. There was no nausea or alopecia. Only two minor responses were seen. Plasma drug levels were insufficient to result in antitumour activity as extrapolated from animal data. Further studies that attempt to increase the bioavailability and improve the therapeutic index are warranted. PMID- 1628378 TI - Added ATP influences some responses of rat synaptosomes to glutamate. AB - ATP added externally to rat synaptosomes activated uptake of both Ca2+ and glutamate which was partially accounted for by the uptake phenomena of synaptic vesicles and mitochondria, as shown by using specific inhibitors of the latter. Increasing concentrations of glutamate stimulated Ca2+ entry linearly, as shown by using 45Ca or a Ca-specific electrode. The processes of glutamate and Ca2+ uptake shared some common features and their ATP-dependence may be correlated with an ouabain-insensitive synaptosomal ectonucleotidase activity measured by a 31P-NMR or a luminometric technique. The ATP hydrolysis catalysed by the synaptosomes was activated by both Ca2+ and glutamate. The present synaptosomal activities may represent a model for studying the modulatory effects of ATP on the glutamatergic neurotransmission. PMID- 1628379 TI - The relation between the synergistic effect of cytostatics and metabolism of V 79B cells in vitro. AB - A single-dose simultaneous application of methotrexate (MTX; 0.002/microgram ml 1) and cisplatin (cis-Pt; 0.0002/microgram ml-1) had a permanent synergistic effect on both synchronized and asynchronous cell populations of V 79B cells. Successive combination of the drugs was manifested synergistically when MTX was applied first. The synchronized cell population was more sensitive to the cytostatics than the asynchronous population. Treatment with MTX alone, or the combination of MTX-cis-Pt, as well as their successive combination with the first drug being cis-Pt, caused gluconeogenesis. PMID- 1628380 TI - Cloturin: effect on energy-producing processes in Ehrlich ascites and P388 murine leukaemia cells. AB - The main purpose of the present investigation was to study the effect of cloturin on aerobic glycolysis, endogenous and exogenous respiration and the level of ATP in both Ehrlich ascites carcinoma (EAC) and P388 murine leukaemia cells incubated in vitro. Also its effect on the level of total (T-SH) and non-protein (NP-SH) thiol groups was investigated. A significant inhibition of aerobic glycolysis was found only in P388 cells after 60 min of cloturin action. Cloturin inhibited both endogenous and exogenous respiration of EAC with succinate as substrate. Cloturin decreased the level of ATP after 2 h incubation in both types of tumour cell. The level of NP-SH was decreased more than that of T-SH in both types of cell. PMID- 1628381 TI - Restricted expression of recombination activating gene (RAG-1) in mouse lymphoid tissues. AB - In an attempt to determine the distribution of recombinase activity in the mouse thymus, spleen and lymph nodes, we used the in situ hybridization method to examine the expression of the recombination activating genes RAG-1 and RAG-2. Expression of RAG-1 was found in most cortical thymocytes but not in the majority of medullary thymocytes. Although hybridization signals of RAG-2 were not as intense as those of RAG-1, the localization of RAG-2 transcripts was similar to that of RAG-1. In the spleen, expression of RAG-1 was found only in limited cells near the sinus, and the majority of the cells within the follicle were negative for RAG-1 transcript. In nude mice, RAG-1-expressing cells were detected in the same regions, which suggests that in situ hybridization signals of RAG-1 in the spleen are due to the cells of B cell origin. In the lymph nodes, expression of RAG-1 was found only in the medullary region. Expression of RAG-2 transcript in the spleen and the lymph nodes, if any, was too faint to determine the specific localization. These results suggest that most of the cortical thymocytes and some cells in the spleen are capable of rearranging T cell receptor genes and immunoglobulin genes, respectively, but the possibility of some other explanation could not be ruled out in RAG-1 expressing cells of the spleen and the lymph nodes. PMID- 1628382 TI - Generation of hydrogen peroxide in resting and activated platelets. AB - The production of hydrogen peroxide was measured by following the oxidation of dichlorofluorescein (DCFH) entrapped into platelets. Resting platelets produced nanomolar quantities of DCF, which was proportional to the concentration of platelets and was steady during 1 h of incubation. A significant increase of basal DCF fluorescence was induced by stimuli namely thrombin, arachidonic acid, the Ca2+ ionophore A23187 and PMA. The effect of agonists has been also measured in the presence of 3-amino-1,2,4-triazole (AT) or N-ethylmaleimide (NEM), inhibitors of catalase and glutathione peroxidase, respectively. A further significant enhancement of DCF produced in stimulated platelets was detected only in the presence of NEM. A correlation was found between the increase in DCF and externally added hydrogen peroxide or the oxidizing species formed by xanthine oxidase plus acetaldehyde. The yield was not affected by superoxide dismutase and was higher in the presence of AT or NEM. A cooperative effect in the presence of both inhibitors was shown. Glutathione peroxidase plus glutathione diminished the level of DCF to basal levels. PMID- 1628383 TI - Differentiation of human peripheral blood monocytes to macrophages is associated with changes in the cellular respiratory burst activity. AB - When phagocytic leukocytes, e.g. neutrophils, monocytes and macrophages, interact with soluble or particulate stimuli, the cells respond with an increased production of reactive oxygen metabolites. This production can be measured with the luminol-amplified chemiluminescence (CL) technique. In the present study, the CL reaction induced in monocyte-derived macrophages was investigated and compared to the responses of neutrophils and monocytes. In systems without additives the CL response of macrophages to soluble stimuli (FMLP, PMA and ionomycin) was very low. Addition of a peroxidase (HRP) to the reaction mixtures resulted in a pronounced increase in CL activity. The cellular CL response in macrophages is thus limited by the amount of peroxidase available. The macrophage response differs qualitatively from the responses of neutrophils and monocytes, in that the intracellular phase of the response is missing. PMID- 1628384 TI - Persisting zones of slow impulse conduction in developing chicken hearts. AB - We performed a correlative electrophysiological and immunohistochemical study of embryonic chicken hearts during the septational period (Hamburger and Hamilton stages 13-31 [2-7 days of incubation]). The analyses yield conclusive evidence for slow conduction, up to 7 days of development, in the outflow tract, in the atrioventricular canal, and in the sinoatrial junction. The conduction velocity remains approximately 1 cm/sec in the outflow tract and increases in the ventricle 20-fold to approximately 20 cm/sec between 2 and 7 days of development. Transmembrane potentials of myocytes in the outflow tract and atrioventricular canal slowly rise (less than 5 V/sec), whereas in the atrium and ventricle, the upstroke velocity is eightfold to 13-fold higher. In the outflow tract, repolarization is completed only after the start of the next cycle. Because of the persistence of slow conduction, the myocardium flanking the developing atria and ventricle is thought to represent segments of persisting "primary" myocardium, whereas the more rapidly conducting "working" myocardium of the ventricle and atria is thought to represent more advanced stages of myocardial differentiation. The persisting primary myocardium was characterized by a continued coexpression of both the atrial and ventricular isoforms of myosin heavy chain. The developing atria and ventricle could be demarcated morphologically from the primary myocardium because the free walls of these segments only express their respective isoforms of myosin heavy chain. The slowly conducting myocardial zones appear to be essential for the function of the embryonic heart because 1) they provide the septating heart with alternating segments of slow and relatively fast conduction necessary for consecutive contraction of the atrial and ventricular segments and 2) their sphincterlike prolonged peristaltic contraction pattern can substitute for the adult type of one-way valves that start to develop at the end of septation. PMID- 1628385 TI - Reflection after delayed excitation in a computer model of a single fiber. AB - Reflection (reflected reentry) is a case of reentry in a one-dimensional structure, divided into proximal and distal segments, in which tissue excited by a wave front propagating in a forward direction is reexcited by electrical activity coming backward from the original direction of propagation. Cases of reflection have been demonstrated in Purkinje fibers and in ventricular muscle preparations containing multiple fibers. Several mechanisms possibly responsible for reflected reentry have been proposed. However, the difficulty in the interpretation of the experimental results, as well as the limited number of different conditions in which reflection was obtained, has kept open the question about conditions and mechanisms for reflection. We have developed a computer model in which reflection occurs. The model involves a single fiber and uses the DiFrancesco-Noble equations for the Purkinje fiber to model the ionic currents. The results show that reflection is possible in a single fiber and that diastolic depolarization (automaticity) is not a requirement for reflection. Active membrane responses to a just-above-threshold stimulus were important for achieving the necessary time delay. Systematic simulations showed further that reflection occurred only when the right coupling conditions linked a short or long proximal fiber to a short distal segment. PMID- 1628386 TI - Mechanism of flecainide's antiarrhythmic action in experimental atrial fibrillation. AB - Class Ic antiarrhythmic drugs are effective in the treatment of atrial fibrillation, but their mechanism of action is unknown. In previous work, we have found that flecainide causes tachycardia-dependent increases in atrial action potential duration (APD) and effective refractory period (ERP) by reducing APD accommodation to heart rate. The present study was designed to evaluate the efficacy and mechanisms of action of flecainide in an experimental model of sustained atrial fibrillation (AF). AF was produced by a brief burst of atrial pacing in the presence of vagal stimulation and persisted spontaneously until vagal stimulation was stopped. The actions of flecainide at two dose levels were compared with those of isotonic glucose placebo in each dog, with a randomized order of blinded drug administration. Flecainide terminated AF in all 16 dogs, while glucose was effective in none (p less than 0.0001). Flecainide increased atrial ERP and reduced conduction velocity in a tachycardia-dependent manner. Doses of flecainide that converted AF resulted in larger changes in ERP than in conduction velocity, increasing the minimum path-length capable of supporting reentry (wavelength). In addition, flecainide reduced regional heterogeneity in ERP and wavelength, an action opposite that of vagal stimulation. Atrial epicardial mapping with a 112-electrode atrial array was used to study the mechanism of flecainide action on AF. Under control conditions, multiple small zones of reentry coexisted. Flecainide progressively increased the size of reentry circuits, decreased their number, and slowed the frequency of atrial activation until the arrhythmia finally terminated; all changes were compatible with an increase in wavelength. We conclude that flecainide terminates atrial fibrillation in this experimental model by causing tachycardia-dependent increases in atrial ERP, which increase the wavelength at the rapid rates characteristic of AF to the point that the arrhythmia can no longer sustain itself. PMID- 1628387 TI - Alpha B-crystallin in cardiac tissue. Association with actin and desmin filaments. AB - alpha B-Crystallin is a 20-kd peptide highly homologous to the small heat-shock proteins. This protein forms soluble homomultimeric complexes (M(r), 300-700 kd) and is very abundant in cardiac muscle cells. In vitro experiments (affinity column chromatography and binding studies with isolated proteins) have shown that alpha B-crystallin interacts directly with actin and, in particular, with desmin filaments. The immunocytochemical localization of alpha B-crystallin within the cardiomyocytes showed that the protein is distributed exclusively in the central region of the I bands (Z lines), where desmin is localized. In vitro studies have further shown that the binding affinity of alpha B-crystallin to actin and desmin filaments increases considerably at slightly acidic pH (6.5) or after a heat treatment (45 degrees C). Moreover, alpha B-crystallin was found to prevent effectively the tendency of actin filaments to form aggregates (i.e., paracrystals) at acidic pH. These in vitro data suggest a protective role of alpha B-crystallin during stress conditions such as ischemia of the heart. Crystallin could prevent the aggregation of filaments, which might occur during the acidification of the cytosol and lead eventually to irreversible structural damage. PMID- 1628388 TI - Hydrogen peroxide-induced cardiovascular reflexes. Role of hydroxyl radicals. AB - Mesenteric ischemia reflexly activates the cardiovascular system. In addition, mesenteric ischemia and reperfusion generate reactive oxygen species. However, the ability of these short-lived reactive oxygen species to generate cardiovascular reflexes is unknown. We therefore investigated cardiovascular reflexes induced by serosal application of hydrogen peroxide (H2O2) to the gallbladder, stomach, or duodenum in anesthetized cats. Serosal application of hydrogen peroxide (44 mumols) to the gallbladder (n = 14) significantly (p less than 0.05) increased mean arterial blood pressure (MAP) by 37 +/- 6 mm Hg, left ventricular dP/dt by 1,893 +/- 416 mm Hg/sec, heart rate by 6 +/- 1 beats per minute, and systemic vascular resistance from 0.34 +/- 0.01 to 0.42 +/- 0.04 peripheral resistance units. The cardiovascular effects were dose-dependent over a range of 0.4 pmol to 132 mumols H2O2. Celiac and superior mesenteric ganglionectomy abolished H2O2-induced cardiovascular effects. Dimethylthiourea (10 mg/kg), a reactive oxygen species scavenger, significantly (p less than 0.05) attenuated 44 mumols H2O2-induced increases in MAP from 36 +/- 3 to 2 +/- 2 mm Hg. Deferoxamine (10 mg/kg) also significantly attenuated 44 mumols H2O2-induced increases in MAP from 40 +/- 7 to 19 +/- 10 mm Hg, but iron-loaded deferoxamine did not. Aspirin (50 mg/kg) did not attenuate H2O2-induced excitation of the cardiovascular system. These data suggest that H2O2 activates abdominal visceral afferents to reflexly stimulate the cardiovascular system by a mechanism involving hydroxyl radicals. Thus, reactive oxygen species could modulate systemic vascular tone by stimulating abdominal visceral afferents during mesenteric ischemia and reperfusion. PMID- 1628389 TI - Effects of complement activation in the isolated heart. Role of the terminal complement components. AB - The mechanisms of the complement-mediated myocardial injury associated with ischemia and reperfusion have not been elucidated fully. Complement activation may directly mediate injury through actions of the anaphylatoxins C3a and C5a or generation of the membrane attack complex C5b-9. A model was developed to examine the direct effects of complement activation on heart function, assess myocardial tissue damage, and determine which complement components mediate tissue injury. Isolated rabbit hearts were perfused with Krebs-Henseleit buffer by using a modified Langendorff apparatus. Human plasma was added to the perfusate as a source of complement. Rabbit tissue activates human complement. Treatment with 6% normal plasma resulted in complement activation as assessed by the generation of Bb, C3a, C5a, and SC5b-9. Functional changes in cardiac performance became apparent 7-15 minutes after plasma addition and developed fully over the next 20 30 minutes. The effects were dependent on the complement titer and included 1) an increase in the end-diastolic pressure, 2) a decrease in the developed pressure, 3) an increase in the coronary perfusion pressure, and 4) an increase in lymphatic fluid formation. These effects were not elicited when an inhibitor of complement activation (FUT-175) was present or when heat-inactivated plasma was used. The effects of complement activation on myocardial function could not be reproduced by treatment with recombinant human C5a, zymosan-activated plasma, or plasma selectively depleted of C8. Myocardial tissue accumulated sodium and calcium and lost potassium as a result of complement activation. Activation caused the release of creatine kinase from myocytes and an increase in the radiolabeled albumin space of the hearts. The data demonstrate that complement activation caused decrements in myocardial function and increased the coronary perfusion pressure and lymphatic fluid flow rate. The effects were not mediated by the anaphylatoxins but were dependent on the distal complement component C8, suggesting that C5b-9 was responsible for the physiological changes. Complement activation directly mediated tissue injury in a manner consistent with plasmalemmal disruption as a result of C5b-9 formation. The data suggest that the C5b-9 complex, which is known to form under conditions of ischemia, may contribute directly to myocardial cell injury. PMID- 1628390 TI - Isolated pulmonary resistance vessels from fetal lambs. Contractile behavior and responses to indomethacin and endothelin-1. AB - A method was developed for recording isometric tension from isolated small arteries (mean internal diameter, 169 microns) and veins (mean internal diameter, 273 microns) of the term fetal lung and was then applied to the study of the mechanisms controlling perinatal pulmonary hemodynamics. The specific purpose was to determine whether the activity of the prostaglandin synthetic system in vessels is conditioned by the oxygen tension and the mode of action of endothelin 1. Both preparations appeared structurally intact and, after normalizing their lumen diameter to either the transmural pressure in vivo (artery) or the contractile capacity of the vessel in vitro (vein), generated force to the activating solution (5 mM Ca2+ in K+ Krebs' solution) in excess of the expected performance under physiological conditions. Treatment with indomethacin (2.8 microM) had no effect on arteries preequilibrated at low PO2 (21 +/- 1 mm Hg); however, the same treatment contracted (approximately 45% of the response to activating solution) arteries at either an intermediate (40 +/- 0.8 mm Hg) or high (70 +/- 0.9 mm Hg) PO2. Endothelin-1 contracted both arteries and veins in a concentration-dependent manner, the threshold being lower with veins (1-10 versus 10-100 pM). Endothelin-1 constriction was also seen in arteries whose tone had been raised with a thromboxane A2 analogue, whereas in thromboxane-treated veins constriction was preceded by a modest relaxation over the range of 1-1,000 pM. The findings with indomethacin lead us to infer that small pulmonary arteries are endowed with a prostaglandin-relaxing mechanism that becomes functional on raising the PO2 from fetal to neonatal levels. Endothelin-1 is a constrictor regardless of the level of intrinsic tone, suggesting a possible role of the peptide in maintaining elevated pulmonary vascular tone in the fetus. PMID- 1628391 TI - Intraluminal flow increases vascular tone and 45Ca2+ influx in the rabbit facial vein. AB - The buccal segment of the rabbit facial vein exhibits a high level of myogenic tone in vitro that develops only in stretched vessel segments between 33 degrees and 44 degrees C. The infusion of physiological salt solution into the lumen of 2 mm-long rabbit facial vein segments induced a flow rate-dependent increase in wall tone, both in the presence (37 degrees C) and absence (30 degrees C) of myogenic tone. In calcium-free physiological solution with EGTA, neither flow nor stretch-induced tone was observed. This flow-induced contraction was associated with an increase in 45Ca2+ unidirectional influx and net uptake. These measurements correlated positively with the level of the associated constrictor responses, both in the presence or absence of myogenic tone. The mean contractile responses to flow (10 and 40 microliters/min), stretch, and histamine (1 microM) were 13%, 28%, 24%, and 33% of the tissue maximal response, respectively. When 45Ca2+ influx was expressed in relation to the force development (45Ca2+ influx per milligram), the amount of calcium entry was dependent on the stimulus. Values for 45Ca2+ influx per milligram in response to flow (10 and 40 microliters/min) and to histamine (1 microM) were not significantly different. The value was significantly lower for the response to stretch. On the other hand, 45Ca2+ net uptake, when expressed per unit force, was similar in response to flow (10 and 40 microliters/min), histamine (1 microM), and stretch.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628392 TI - Endogenous calcitonin gene-related peptide mediates nonadrenergic noncholinergic depressor response to spinal cord stimulation in the pithed rat. AB - The role of endogenous calcitonin gene-related peptide (CGRP) in the nonadrenergic noncholinergic depressor response to spinal cord stimulation was studied in the pithed rat in vivo. Pithed rats were given hexamethonium (2 mg/kg per minute i.v.) to block autonomic outflow, and mean blood pressure was artificially maintained at approximately 100 mm Hg with methoxamine (10-15 micrograms/kg per minute i.v.). Electrical stimulation of the spinal cord at the level of the lower thoracic vertebra (T9-12) caused a fall in blood pressure in a frequency-dependent (0.5-10 Hz), voltage-dependent (2.5-50 V), and pulse duration dependent (0.25-8 msec) manner. The heart rate did not change during the depressor response. The depressor response was long lasting, and the maximum response was elicited by stimulation at 4-6 Hz. The neurotoxin tetrodotoxin (100 micrograms/kg i.v.) abolished the depressor response to spinal cord stimulation, whereas treatment with propranolol (0.5 mg/kg per minute i.v.), atropine (0.05 mg/kg per minute i.v.), or a combination of pyrilamine (0.5 mg/kg per minute i.v.) and cimetidine (0.5 mg/kg per minute i.v.) did not affect the response. In pithed rats treated with capsaicin (total dose of 500 mg/kg s.c.), spinal cord stimulation caused a slight depressor response. Exogenous CGRP, but not acetylcholine, isoproterenol, histamine, or substance P, caused a sustained fall in blood pressure that mimicked the spinal cord stimulation-induced depressor response. Continuous infusion of CGRP[8-37] (60 nmol/kg per minute i.v.), a CGRP receptor antagonist, markedly inhibited the depressor responses not only to spinal cord stimulation but also to exogenous CGRP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628393 TI - Time course of left ventricular function after cardiac denervation in conscious dogs. AB - The time course of left ventricular (LV) function was compared in normal (N) and cardiac-denervated (CD) dogs over an 8-week period after instrumentation with solid-state LV pressure gauges and three pairs of ultrasonic crystals to measure LV long and short axes and wall thickness. Baseline LV systolic, end-systolic, and end-diastolic pressures did not differ in N and CD dogs. Heart rate was higher (p less than 0.01) and LV dP/dt was lower (p less than 0.05) in CD dogs. LV short-axis shortening, shortening fraction, velocity of circumferential fiber shortening, and ejection fraction were consistently lower (p less than 0.01) in CD dogs. With angiotensin II to increase LV afterload, relations of LV short-axis shortening, shortening fraction, velocity of circumferential fiber shortening, and ejection fraction to average LV systolic wall stress were shifted downward (p less than 0.01) in CD dogs at 2, 4, and 8 weeks. Relations of LV short-axis shortening to LV end-diastolic wall stress also differed (p less than 0.01) in N and CD dogs. Ganglionic blockade abolished differences in LV function between N and CD dogs during elevated LV systolic wall stress with angiotensin II. Thus, in conscious dogs, cardiac denervation results in a sustained reduction of LV function over a wide range of ventricular loading conditions. PMID- 1628394 TI - Cultured rat aortic vascular smooth muscle cells digest naturally produced extracellular matrix. Involvement of plasminogen-dependent and plasminogen independent pathways. AB - Vascular smooth muscle (VSM) cell migration and proliferation play a major role in the development of atherosclerotic lesions, graft occlusion, and restenosis after angioplasty. Cell migration implies the digestion of the surrounding extracellular matrix. Cell-associated proteolysis has been extensively studied in neoplastic and inflammatory cells, but very little is known about the proteolytic properties of VSM. We have evaluated the ability of rat cultured VSM cells to solubilize [3H]amino acid-labeled extracellular matrices produced by bovine VSM. When plated at a density of 30,000 cells per well in 24 multiwell plates, VSM cells were able to solubilize 63.3 +/- 7.0% of the extracellular matrix after 10 days in culture. Extracellular matrix digestion occurred also when the cells were cultured in plasminogen-depleted serum but was higher in the presence of 10 micrograms/ml purified plasminogen (net percent digestion after the subtraction of the appropriate control, 8.6 +/- 3.0% versus 21.2 +/- 3.5% after 3 days in culture, p less than 0.005, respectively). The involvement of other enzymes in addition to plasmin is confirmed by the ability of VSM cells to degrade extracellular matrices from which the plasmin-sensitive component was removed with plasmin pretreatment. Rat VSM cells were able to solubilize 52.3 +/- 2.0% of this residual extracellular matrix-associated radioactivity after 6 days in culture versus 26.1 +/- 1.5% in the control dishes (p less than 0.01, n = 5). Cell contact was required for extracellular matrix degradation: cell-conditioned medium did not have any effect on extracellular matrix digestion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628395 TI - Physiological hyperinsulinemia inhibits myocardial protein degradation in vivo in the canine heart. AB - Myocardial protein turnover in vivo was examined in anesthetized dogs following a 16- or 36-hour fast and again during a hyperinsulinemic (2 mU/kg per minute) euglycemic clamp with or without amino acid replacement or during saline infusion. We measured myocardial phenylalanine balance and rates of protein synthesis and degradation, using the extraction of intravenously infused L-[ring 2,6-3H]phenylalanine and the dilution of its specific activity across the heart at isotopic steady state. After both a 16-hour (n = 19) and 36-hour fast (n = 10), there was net myocardial release of phenylalanine indicated by the negative balances for phenylalanine of -52 +/- 9 (p less than 0.001) and -38 +/- 9 (p less than 0.005) nmol/min, respectively. Overall, the basal rate of myocardial protein degradation was lower in the 36-hour-fasted animals (81 +/- 13 versus 121 +/- 12 nmol/min, p less than 0.05). Myocardial phenylalanine balance and rates of protein synthesis and degradation did not change during insulin and glucose infusion in the 36-hour-fasted animals (n = 10). In these animals, there was a 30 40% decline in plasma amino acid concentrations, including branched chain (p less than 0.001) and essential amino acids (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628396 TI - Biomechanical properties of reperfused transmural myocardial infarcts in rabbits during the first week after infarction. Implications for left ventricular rupture. AB - Left ventricular (LV) rupture potential was studied after transmural myocardial infarction (MI) in rabbits by measuring 1) the tensile strength of infarcted tissue strips, 2) the force required to initiate a tear (tear threshold) in the central infarcted region, and 3) the intracavitary pressure required to rupture the infarcted ventricle. During the first week after MI, infarcts resulting from a permanent coronary occlusion were compared with infarcts reperfused "late" (i.e., 3 hours) after coronary occlusion with a resultant hemorrhagic transmural infarct but no reduction in infarct size. The reperfused hemorrhagic infarcted strips had less tensile strength than strips from permanently occluded infarcts in the initial 24 hours after MI (16 +/- 1 versus 24 +/- 3 g/mm2, p less than 0.05), but the tear threshold and response to increased LV pressure were not influenced by infarct reperfusion at this time. By 3 days after MI, reperfused infarcts had equal tensile strength, had greater resistance to infarct tearing, and could withstand a greater LV distending pressure compared with permanently occluded infarcts. By 5 days after MI, reperfused infarcts maintained a greater tear threshold but had less tensile strength than permanently occluded infarcts, although all infarct values were equivalent or greater than normal LV values. By 7 days after MI, reperfused and permanently occluded infarcts were equally strong by all measurements. Thus, late reperfusion of transmural infarcts increased resistance to infarct tearing and LV rupture above that of nonreperfused permanently occluded infarcts by 3 days after MI and enhanced tissue strength after an initial 24-hour vulnerable period. These findings suggest that late reperfusion may accelerate myocardial healing after MI. PMID- 1628397 TI - Basal metabolism adds a significant offset to unloaded myocardial oxygen consumption per minute. AB - Myocardial oxygen consumption (MVO2) includes components for 1) mechanical energy generation, 2) activation, and 3) basal metabolism. Whereas the first two components are expected to increase in proportion with heart rate, a significant basal level of metabolism would consume oxygen even if the heart rate were zero. Contrary to this expectation, however, a previous study reported that, during unloaded beats, MVO2 per beat (which includes basal metabolism) was independent of heart rate. Accordingly, unloaded MVO2 per minute would extrapolate to zero at zero heart rate; this result is unexpected considering basal metabolism. To resolve this inconsistency, we varied heart rate over a wide range after inducing atrioventricular block in eight isolated cross-circulated canine hearts that contracted isovolumically. We examined whether a term representing rate independent basal metabolism was needed to describe MVO2 per minute. Mechanical energy generated by the left ventricle was evaluated from the pressure-volume area, which was altered by changing isovolumic ventricular volume over at least five levels at each heart rate. Contractility, evaluated by the slope of the end systolic pressure-volume relation, did not vary significantly with heart rate in this study. In contrast to the previous report, unloaded MVO2 per beat (i.e., MVO2 extrapolated to a pressure-volume area of zero) was not constant but fell monotonically with increases in heart rate in every heart. We considered that this trend was caused by a significant rate-independent basal level of MVO2 per minute. Multiple linear regression analysis confirmed that this rate-independent basal term differed significantly from zero in seven of the eight hearts studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628398 TI - Mechanism of ergonovine-induced hyperconstriction of the large epicardial coronary artery in conscious dogs a month after arterial injury. AB - This study investigated the mechanism of ergonovine-induced hyperconstriction of coronary artery in conscious dogs that had undergone endothelial denudation one month earlier. The diameter of the large epicardial coronary artery was continuously measured by a sonomicrometer in 12 dogs in which two pairs of 10-MHz piezoelectric crystals had been surgically implanted at the denuded and nondenuded sites of coronary arteries. A month after the endothelial denudation, intravenous ergonovine (0.01, 0.1, 0.3, and 1.0 mg) produced transient dilation followed by dose-dependent constriction. The degrees of dilation were comparable between the denuded and nondenuded sites. The magnitudes of constriction induced by ergonovine were significantly larger in the denuded site than in the nondenuded site: the percent reductions in diameter evoked with 0.3 mg ergonovine were 14.4 +/- 2.3% and 3.8 +/- 0.8% (p less than 0.01) at the denuded and nondenuded sites, respectively. The magnitudes of constriction induced by intravenous phenylephrine (0.02, 0.06, and 0.2 mg) were comparable in the denuded and nondenuded sites. Methysergide (a nonselective serotonergic blocker) in a dose of 0.5 mg/kg significantly inhibited vasoconstriction induced by ergonovine (0.3 mg) from 13.1 +/- 1.1% to 2.7 +/- 1.0% (p less than 0.01) at the denuded site and from 4.2 +/- 0.6% to 0.8 +/- 0.3% (p less than 0.05) at the nondenuded site. Diltiazem (1.0 mg/kg) selectively inhibited the ergonovine-induced hyperconstriction. Ketanserin (0.5 mg/kg), prazosin (1.0 mg/kg), or indomethacin (5.0 mg/kg) did not prevent the ergonovine-induced hyperconstriction. Histological study revealed intimal thickening and regenerated endothelium in the denuded site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628399 TI - Indirect relation between rises in oxygen consumption and left ventricular output at birth in lambs. AB - To examine the relation between increased newborn oxygen requirements and the postnatal rise in cardiac output, we measured left ventricular (LV) output, organ blood flows, and whole-body oxygen consumption using radioactive microspheres in late-gestation sheep fetuses and in the same animals 1 and 4 hours after cesarean section delivery. LV output rose from 264 +/- 23 ml.min-1.kg body wt-1 in fetuses to 444 +/- 33 ml.min-1.kg body wt-1 in lambs at 1 hour after delivery (p less than 0.005) and was unchanged at 4 hours after delivery. This rise in LV output was associated with a more than fourfold increase in the LV flow contribution to tissues situated distal to the ductus arteriosus (fetus, 51 +/- 9 ml.min-1.kg body wt-1; lamb, 226 +/- 22 ml.min-1.kg body wt-1; p less than 0.005), which were mainly perfused by the right ventricle in utero. However, average blood flow to body tissues was similar in fetuses (37 +/- 4 ml.min-1.100 g tissue-1), 1-hour lambs (39 +/- 4 ml.min-1.100 g tissue-1), and 4-hour lambs (40 +/- 5 ml.min-1.100 g tissue-1). Oxygen consumption increased by 58%, from 7.84 +/- 0.43 ml.min-1.kg body wt-1 in fetuses to 12.38 +/- 2.4 ml.min-1.kg body wt-1 in 1-hour lambs (p less than 0.01), and was unchanged in 4-hour lambs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628400 TI - Changes in extracellular and intracellular pH in ischemic rabbit papillary muscle. AB - The extracellular pH (pHo) and intracellular pH (pHi) were simultaneously measured with H(+)-sensitive microelectrodes in the rabbit papillary muscle during normal arterial perfusion and no-flow ischemia. The preparation was kept in an artificial gaseous atmosphere (N2 and CO2 during ischemia) without a surrounding fluid layer. Cylindrical muscles of small diameters (less than 1.0 mm) were selected to prevent major diffusion gradients of CO2 within the muscle cylinder during ischemia. In normal perfusion with CO2/HCO3(-)-buffered blood at PCO2 of 35 mm Hg, pHi was 7.03 +/- 0.03. During early ischemia, extracellular acidification was much more prominent than intracellular acidification. Consequently, the transmembrane pH gradient reversed (pHo less than pHi) at approximately 8 minutes. At 14 minutes of ischemia, pHo was 6.64 and pHi was 6.93. A moderate increase in PCO2 from 35 to 67 mm Hg before ischemia enhanced intracellular acidification in ischemia. Simulation of CO2 accumulation (increase of PCO2 in the surrounding atmosphere), as encountered in midmural ventricular layers during in vivo ischemia, produced a significant decrease of pHo (6.30 versus 6.64) and pHi (6.65 versus 6.93) at 14 minutes of ischemia. The presence of red blood cells in the intravascular space after arrest of coronary perfusion showed a pronounced effect on extracellular and intracellular acidosis. If the muscles were perfused with CO2/HCO3(-)-buffered perfusate in the absence of red blood cells, the changes of pHo and pHi were significantly larger (pHo, 6.00 versus 6.64; pHi, 6.46 versus 6.93 at 14 minutes) during ischemia. Actively developed force during ischemia was not significantly influenced by conditions modulating pHi. It decreased by 82% after 5 minutes, even when no significant change of pHi was recorded. By contrast, ischemic contracture was dependent on intracellular acidification. It developed earlier in the absence of red blood cells or with low extracellular buffer capacity. It is concluded that during acute myocardial ischemia 1) extracellular acidification exceeds intracellular acidification, 2) the decrease in pHi is inhomogeneous because of local variation in CO2 accumulation and diffusion, 3) the decrease in pHi is relatively small in the presence of red blood cells, and 4) the development of ischemic contracture but not the early decline in active tension is sensitive to changes in pHi. PMID- 1628402 TI - EEG and evoked potentials in HIV-infected children. AB - Forty-seven HIV-seropositive children were investigated by EEG and evoked potentials (BAEP, SEP). Twenty-three children were symptomatic (P2), 8 seropositive without symptoms (P1), and 16 children were less than 15 months of age (P0). Some of them were investigated at different stages of HIV infection. During the neonatal period, 7 newborns of drug-addicted mothers had seizures and frequent spikes and sharp waves in their EEGs. Among (P2) children 6/23 showed background slowing and 1 had rhythmic theta activity (6 with and 1 without neurological symptoms). In BAEP, bilateral prolonged interpeak latencies (IPL) were found in 1 child with severe AIDS encephalopathy. Side differences greater than or equal to 0.4 ms in IPL were seen in 2 (P2), 1 without and 1 with neurological symptoms. A late onset was seen in 2 (P1) and 4 (P2) children. Median SEPs were normal in 24/26 patients; N20/N13 amplitude ratio was reduced in 2 (P1) patients. EEG and BAEP revealed nonspecific abnormal features in HIV encephalopathy. The the progression of the disease. However, also in the symptomatic group, normal results of EEG and BAEP dominated. SEP in the symptomatic group revealed only normal values. For monitoring the effectiveness of AZT treatment in HIV encephalopathy, EEG seems to be a relevant investigation; for evoked potentials more data and experience are needed. PMID- 1628401 TI - Impaired myogenic responsiveness of renal microvessels in Dahl salt-sensitive rats. AB - The mechanisms mediating abnormal renal autoregulation in Dahl salt-sensitive (DS) rats have not been fully defined. In the present study, we assessed myogenic responsiveness of interlobular arteries (ILAs), afferent arterioles (AAs), and efferent arterioles in isolated perfused hydronephrotic Dahl rat kidneys. Dahl rats were divided into four groups according to strain (Dahl salt-resistant [DR] or DS rats) and dietary sodium manipulation (rats fed low or high salt diets). Systolic blood pressure was elevated only in DS rats fed the high salt diet (202 +/- 4 mm Hg, p less than 0.05). Myogenic responses were obtained by stepwise elevation of renal arterial pressure. Vessel diameters were determined by computer-assisted videomicroscopy. Preglomerular microvessels of DS and DR rats responded differently to changes in renal arterial pressure. AAs and ILAs manifested diminished myogenic responsiveness to increasing renal arterial pressure in DS rats compared with DR rats (p less than 0.05). Both AAs and ILAs in DS rats manifested a higher threshold pressure for eliciting myogenic responses and a decrease in maximal pressure-induced vasoconstriction. The sensitivity of the AA myogenic response to nifedipine was enhanced in DS rats compared with DR rats (p less than 0.05). For rats fed the high salt diet, preglomerular vessels exhibited reduced myogenic responsiveness in both strains. In contrast to preglomerular microvessels, efferent arterioles from all four groups of rats failed to exhibit pressure-induced vasoconstriction. Our data suggest that diminished myogenic responsiveness of AAs and ILAs in DS rats contributes to impaired renal autoregulation in this strain. PMID- 1628403 TI - Sleep electroencephalogram at the early stage of Creutzfeldt-Jakob disease. AB - We describe sleep EEG studies in three patients at the early stage of Creutzfeldt Jakob disease. Little work has been devoted to the study of the sleep EEG in the course of the CJ disease: disorganized sleep architecture was noted, associated with a decrease in stage 4 and an almost complete disappearance of the REM stage. Our patients were considered to have normal stage 2; yet spindles and K complexes were rare at this stage. No evolution towards stage 4 was noted. The percentage of rapid eye movement sleep was significantly low in two cases and normal in one case. Sleep disturbances in the other dementing disorders are reported. PMID- 1628404 TI - Can somatosensory evoked potentials predict outcome from coma? AB - Long-term somatosensory evoked potential (SEP) recordings for a period of 2 1/2 years are reported for a patient rendered comatose from hypoxic encephalopathy. Findings are compared with previously published reports on poor outcome associated with bilaterally absent cortical responses. In the present case, the patient was admitted with poor neurological status but has preserved cortical responses bilaterally throughout his course until his final recovery and return to previous employment. Somatosensory cortical responses when bilaterally absent are universally associated with poor outcome; however, when persistently present they can indicate hope of recovery despite poor clinical status on admission. PMID- 1628405 TI - Subclinical cognitive deficits in cancer patients: a preliminary P300 study. AB - A preliminary study of event related potentials (P300) in a group of 16 cancer patients, without cerebral metastases or focal neurological deficits, is being reported. As compared to a group of 28 normal adults, 9 out of 16 cancer patients were found to have prolonged P300 latencies, and 6 made more than two errors in their cognitive performance. These subclinical cognitive impairments in cancer patients may be related to some remote effects of cancer. These patients had not undergone any chemotherapy or radiation therapy prior to P300 studies. Further studies in a larger group of patients with gynecological cancer are being conducted. PMID- 1628406 TI - Spindle activity in the waking EEG in older adults. AB - Sleep spindles are an EEG sign of light sleep under physiological conditions. We reported the simultaneous occurrence of sleep spindles and alpha activity in the waking EEG in 12 patients with a mean age of 59.0 years. Most of the patients were diagnosed as cerebrovascular disorders such as cerebral arteriosclerosis, transient ischemic attack and vascular dementia. The mean alpha frequency in the presence of WSA significantly decreased by 1.5 Hz. The frequency and spatial distribution of waking spindle activity were similar to those of sleep spindles. In our cases, at least the two factors of cerebrovascular involvement and older adults were considered to be primarily responsible for the intrusion of sleep spindles into wakefulness (presumably a state close to very light drowsiness) due possibly to the instability of sleep-waking cycle regulation. PMID- 1628407 TI - Cassette EEG sleep recordings in Gilles de la Tourette syndrome. AB - Tourette syndrome (TS) patients often complain of sleep problems, and questionnaire studies indicate that sleep disturbance is frequent. Decreased slow wave sleep and increased awakenings have been reported in laboratory polysomnography in TS patients, and a serotoninergic disorder of arousal has been postulated. We recorded outpatient sleep in 20 patients newly diagnosed with TS utilizing a 4-channel cassette EEG system. The newly-diagnosed patients were predominantly male, and ranged in age from 10 to 36 years. Some had taken psychotropic medications in the past, but none had been treated systematically for TS. Seven patients had chronic tics only, 8 had tics and attention deficit hyperactivity, and 5 had tics plus obsessions and compulsions. None had other medical, neurologic, or psychiatric disorders. All were nocturnal sleepers, and were recorded in their usual sleeping environments and routines. TS patients had reduced sleep, decreased sleep efficiency, increased awakenings, and decreased slow wave sleep. Tic patients had increased nocturnal awakenings and movements, particularly those who had tics during sleep. Sleep fragmentation and loss of slow wave sleep was most marked in TS patients with attention deficit hyperactivity. Sleep latency was increased, REM sleep reduced, and REM sleep latency decreased in TS patients with obsessions and compulsions. These findings accord with previous reports of sleep disturbance in TS, and suggest that these disturbances may vary with TS symptoms. Chronic tics may persist in sleep and cause awakenings, TS with attention deficit may be associated with a disorder of arousal and alertness, and obsessions and compulsions may be manifestations of a biochemical disturbance involving paradoxical sleep. PMID- 1628408 TI - Prior head injury accounts for the heterogeneity of the alcohol-epilepsy relationship. AB - Fifty-five adult male patients with alcoholism and seizures were divided into three groups. In group I, all seizures were consistently produced by alcohol withdrawal (N = 16); in group II, some seizures were clearly precipitated by alcohol withdrawal and others were not (n = 18); and in group III none of the seizures had a consistent relationship with drinking (N = 21). The three groups were compared for age, frequency of seizures, compliance, Bear-Fedio and Boston Naming scores, those for memory of words and faces, and finger-tapping scores, and neuropsychological impairment ratings as well as EEG background frequencies. The incidence of severe head injury preceding the onset of seizure disorder was significantly higher in groups II and III. This was further supported by a greater prevalence of asymmetric alpha rhythm, abnormal CT scans and multiple seizure types in those two groups. These data indicate that a prior head injury is a major variable accounting for the heterogeneity of the alcohol-epilepsy relationship. PMID- 1628409 TI - Hot water epilepsy. AB - The clinical and EEG features of 10 patients with hot water epilepsy were presented. Eight of the 10 cases were male. The mean age of onset was 4.7 years. In four patients partial and in six cases generalized seizures were seen. Three patients also had non-hot water precipitated seizures. Interictal EEGs showed generalized abnormalities in eight and focal abnormalities in two cases. CT was performed and found normal in two patients. Anticonvulsant therapy was instituted for all patients. In six cases with adequate follow-up, complete remission was obtained in four and the frequency of the seizures was decreased in two, with anticonvulsant therapy. PMID- 1628410 TI - Nitrendipine 20 mg once daily versus nicardipine slow release 40 mg twice daily in mild essential hypertension: evaluation by 24-hour ambulatory blood pressure monitoring. AB - The extent and duration of the blood pressure (BP) lowering effect of 20 mg nitrendipine (NIT) once daily and 40 mg nicardipine slow release (NIC) twice daily were compared in 12 men (aged 39-55 years) with mild essential hypertension according to a randomized, cross over study. Twenty-four-hour non invasive ambulatory BP monitoring (Spacelabs 5200) was performed at the end of a 2-week placebo run-in and after 4 weeks of each active treatment; automatic BP measurements were programmed at 15-min intervals. Both treatments significantly (p less than .01) reduced mean 24-hour and daytime systolic (SBP) and diastolic (DBP) BP, but had different effects on daytime BP profiles. NIT decreased SBP and DBP (p less than .05) in 5 out of 8 two-hour subperiods (from 8 a.m. to 6 p.m.), followed by a loss of effect; NIC reduced SBP and DBP (p less than .05) in 7 out of 8 two-hour subperiods (from 8 a.m. to 10 p.m.). During the night-time, NIT reduced mean SBP (p less than .05) and NIC both mean SBP and DBP values (p less than .05; p less than .05 vs NIT for SBP). Heart rate was not affected by either treatment. Thus, after short-term treatment in mild essential hypertensives nitrendipine once daily was not as effective as nicardipine slow release twice daily in reducing blood pressure throughout the 24 hours. PMID- 1628411 TI - Electrophysiological responses of angiotensin peptides on the rat isolated nodose ganglion. AB - Previous autoradiographic studies have identified angiotensin II (AII) binding sites over the nodose ganglion and along the vagal afferent neurons. In the present study, we examined whether these binding sites are functional receptors by measuring d.c. potential changes by extracellular recording techniques in the rat isolated nodose ganglion preparation in response to superfusion of angiotensin peptides. It was found that AII, as well as AI and AIII elicited concentration-dependent depolarisation of the nodose ganglion. However, the amino terminal angiotensin heptapeptide, A(1-7), failed to evoke any significant response. The AII receptor antagonist, saralasin had no intrinsic activity, but caused a concentration-dependent blockade of AII-induced depolarisation. This study provides evidence for direct neuronal effects of angiotensin peptides on rat vagal afferent neurons. Moreover, this preparation is a relatively convenient one in which to study functional neuronal AII receptor mechanisms on central or peripheral terminals of vagal sensory neurons. PMID- 1628412 TI - Chlorthalidone reduces vascular hyperresponsiveness in DOCA-salt hypertensive rats. AB - The mechanisms of anti-hypertensive effect of diuretics remain unknown. The purpose of this study was to test the hypothesis that long-term treatment with chlorthalidone decreases the responsiveness of resistance vessels to neurohormones. The study was performed in deoxycorticosterone acetate (DOCA)-salt hypertensive rats with and without treatment with chlorthalidone (Chlor. 8 mg/day, for 20 days). Resting mean arterial pressure in freely moving state was significantly reduced in DOCA-salt-Chlor rats when compared to DOCA-salt rats (116 +/- 3 vs 147 +/- 7 mmHg, respectively). Chlorthalidone treatment reduced the high plasma sodium content observed in DOCA-salt rats to the same levels observed in normotensive control groups. Results obtained in isolated perfused mesenteric arteries showed: a) the increase in perfusion pressure elicited by norepinephrine (NE), serotonin (SE) and vasopressin (VP) was significantly greater in DOCA-salt than in DOCA-salt + Chlor rats or control normotensive rats; b) the endothelium removal increased the pressor responses to NE, SE and VP in a similar way in all groups. These data provide evidence that long-term chlorthalidone treatment reduces vascular hyperresponsiveness to these neurohormones. In addition, these results indicate that this reduction in vascular hyperresponsiveness, associated with a decrease in extracellular sodium level, could be a possible mechanism by which the diuretics reduce the high blood pressure. PMID- 1628413 TI - Renal nerve-mediated proximal tubule solute reabsorption contributes to hypertension in spontaneously hypertensive rats. AB - Renal nerve activity increases (Na+, K+)-ATPase activity and contributes to the development of hypertension in young SHR. The present study was designed to examine the effect of sodium intake on blood pressure and proximal tubule solute reabsorption in sham-operated or renal denervated, 5-week old SHR and WKY. Three week old SHR and WKY rats underwent sham surgery or renal denervation with 10% phenol and were maintained for 10 days on either a 0.6% or 2.2% NaCl diet. Blood pressure was obtained by indirect tail cuff measurements during this interval. Of the eight groups, only sham-operated SHR on a high sodium diet had hypertension, 122.0 +/- 4.2 mm Hg vs. 98.7 +/- 3.3 mm Hg (mean for remaining groups). Renal plasma flow (RPF), glomerular filtration rate (GFR), and the fractional excretion of lithium (FELi) were determined in rats maintained on a 2.2% sodium diet at 5 weeks of age. FELi was less in sham-operated SHR, 5.3 +/- 0.7%, compared to WKY, 9.4 +/- 2.8% (P less than 0.02). Furthermore, denervation ameliorated the reduced FELi in SHR, 10.2 +/- 1.2%, without affecting FELi in WKY. RPF and GFR were similar between sham-operated and renal denervated SHR and WKY. No significant difference could be detected in net sodium balance between WKY and SHR during this period. These findings demonstrate 1) from the basis of FELi, young SHR, of this strain, exhibit enhanced proximal tubule solute reabsorption and hypertension while on a high sodium diet and, 2) renal denervation ameliorates both the enhanced proximal tubule solute reabsorption and the early development of hypertension. These data support the concept that renal nerve activity of young SHR is augmented and contributes to the development of hypertension by enhancing salt retention. PMID- 1628415 TI - Selected abstracts from the 14th annual meeting of the Japanese Societies of Hypertension. PMID- 1628414 TI - Insulin attenuates vasoconstriction by noradrenaline, serotonin and potassium chloride in rat mesenteric arterioles. AB - We investigated the effect of insulin on the vascular reactivity to noradrenaline, serotonin and potassium chloride in rat mesenteric resistance arterioles in vitro. Mesenteric artery segments were placed in a myograph system. Sensitivity to noradrenaline, serotonin and KCl was tested after an equilibration at 37 degrees C. Thereafter, arteries were incubated with buffer alone or with insulin (40, 100, 250 and 400 mU/ml) for one hour at 37 degrees C. Sensitivity to the three vasoconstrictors was retested. Incubation with noradrenaline, serotonin and KCl resulted in a dose dependent increase in wall force. Exposure with buffer did not change the shape of the dose-response-curve. The same was true for the lowest dose of insulin (40 mU/ml). However, incubation with insulin at concentrations of 100, 250 and 400 mU/ml led to a reduction in wall force by 37 77%. The reduction in the slope of the curve and the maximal response suggest a non-competitive inhibition. Supraphysiological doses of insulin attenuate the vasoconstriction by noradrenaline, serotonin and KCl in rat mesenteric arteries in vitro. PMID- 1628416 TI - In vivo clearance by the mononuclear phagocyte system in humans: an overview of methods and their interpretation. AB - The mononuclear phagocyte system (MPS) is responsible for the elimination of foreign material, effete autologous material and immune complexes. To study the relationship between MPS function and human disease, several test substances have been developed, and used to determine the clearance capacity of the MPS in human subjects in vivo. These test substances and the multitude of factors that influence the elimination of these substances (and complicate the interpretation of the test results) are discussed. Use of these probes has provided important new insights, that may lead to the development of treatment modalities by which MPS function is modified in order to influence disease processes more effectively. PMID- 1628417 TI - IL-8 as a circulating cytokine: induction by recombinant tumour necrosis factor alpha. AB - Tumour necrosis factor-alpha (TNF-alpha) is a pivotal cytokine at the centre of a cascade of cytokines and inflammatory mediators which modulate the host response to infection and trauma, and in particular the metabolic changes resulting in shock and subsequent multi-organ failure. The cytokine IL-8--predominantly an activator and chemotactic factor for circulating polymorphonuclear neutrophil leucocytes--is produced in response to TNF-alpha in vitro, and high circulating levels of IL-8 are found in septic primates. We have studied the release of IL-8 into the circulation of subjects with chronic hepatitis B undergoing a 10 week pilot trial of recombinant TNF-alpha (rTNF-alpha) therapy in doses of 15-100 micrograms/m2. A marked dose-dependent increase in plasma IL-8 levels was seen commencing at 30-60 min after the start of rTNF-alpha infusion and peaking between 2 and 3 h (mean peak level 4300 ng/l). The temporal pattern of IL-8 production exactly echoed that of IL-6, another component of the cytokine cascade, but peak plasma levels of IL-8 were up to 17 times higher than those of IL-6. This study confirms in vitro data suggesting that IL-8 is a component of the acute circulating cytokine cascade with a potential role in the modulation of the acute immune and metabolic response to infection and trauma. PMID- 1628418 TI - Monocyte cytokine secretion induced by chemically-defined derivatives of Klebsiella pneumoniae. AB - The capacity of a K. pneumoniae membrane proteoglycan (Kp-MPG) and four of its chemically defined derivatives to activate human monocytes was studied by measuring immunoreactive IL-1 beta, IL-6 and tumour necrosis factor-alpha (TNF alpha) in culture supernatants. Monocyte culture supernatants were also tested for their comitogenic activity on concanavalin A-stimulated thymocytes and for their cytotoxic activity on the mouse fibroblastic L929 cell line. The four Kp MPG derivatives were: (i) an acylpoly(1-3)galactoside (APG); (ii) an APG preparation submitted to acid hydrolysis which removed all fatty acids but left intact the galactose chain of APG (GC-APG); (iii) a preparation obtained by mild alkaline hydrolysis, containing additional ester-linked C14 and C16 fatty acids bound to the APG molecule (EFA-APG); and (iv) a polymer of the latter compound (APG pol). Kp-MPG induced the synthesis of IL-1 beta, IL-6 and TNF-alpha with dose-responses and kinetics similar to those of Salmonella minnesota lipopolysaccharide (Sm-Re-LPS). APG pol and EFA-APG induced the secretion of the three cytokines with lower potency than Kp-MPG or Sm-Re-LPS. APG did not trigger any detectable cytokine production and GC-APG induced only borderline and inconsistent responses. Our data demonstrate the critical role of ester-linked C14 and C16 fatty acids in the triggering of monocyte response to Kp-MPG derivatives. PMID- 1628419 TI - Cellular immune response to the cell walls of Mycobacterium leprae in leprosy patients and healthy subjects exposed to leprosy. AB - Cell walls of M. leprae consist of complex arrangements of carbohydrate, lipid, peptidoglycan and protein molecules. Recently, extractable proteins of a wide range of molecular weights were identified as components of the cell wall. We have examined the cellular immune responses of Nepali leprosy patients to a cell wall preparation of M. leprae enriched for these proteins. Strong lymphocyte proliferative responses to the antigens were present in half of the paucibacillary leprosy patients and in the majority of healthy control subjects with occupational exposure to leprosy. Patients with multibacillary disease responded poorly and patients with tuberculosis had intermediate responses. Proliferative responses to the cell wall protein fraction were strongly correlated to the proliferative responses to sonicates of the whole leprosy bacillus. Immunization of mice with cell wall proteins resulted in inhibition of growth of M. leprae following foot-pad inoculation with viable organisms. Therefore cell-mediated immune responses to the extractable proteins of the cell wall may play a role in protective immunity against M. leprae infection. PMID- 1628420 TI - T cell regulation of the chronic peritoneal neutrophilia during mycobacterial infections. AB - Intraperitoneal infection of mice with mycobacteria induces the persistent mobilization of neutrophils to the infected peritoneal cavities. The recruitment of the neutrophils was mediated by the immune system since it was enhanced by immunization and reduced in T cell-deficient nude and SCID mice. Anti-mitotic treatments with cyclophosphamide or X-rays led to a reduction in the number of mononuclear cells in the peritoneal cavity of infected mice, followed by a reduction in neutrophil numbers despite the presence of a normal circulating pool of neutrophils. The depletion of T cells with antibodies during mycobacterial i.p. infection led to a reduction in the number of neutrophils. Such a reduction was more extensive if the antibodies were administered early. Our data suggest that T cells are partially involved in the direct recruitment of neutrophils during chronic mycobacteriosis but they also play a role in the priming of other cell types for the mobilization of these phagocytes. PMID- 1628421 TI - Secretion of Toxoplasma gondii-specific antibody in vitro by peripheral blood mononuclear cells as a new marker of acute toxoplasmosis. AB - Antigen-specific antibody secretion in vitro by peripheral blood mononuclear cells (PBMC) reflects an in vivo stimulation of the immune system by the antigen. Primary infection of immunocompetent patients with T. gondii causes an acute infection followed by chronic toxoplasmosis. We examined in vitro anti-Toxoplasma antibody production by PBMC during the acute and chronic phases of toxoplasmosis. PBMC from patients with acute or chronic toxoplasmosis and seronegative subjects were cultured for up to 6 days. Anti-Toxoplasma antibodies were assayed in supernatants by ELISA and immunoblotting. Anti-Toxoplasma antibodies were detected in supernatants of PBMC from 29 pregnant women who seroconverted during gestation. PBMC from 17 patients who had chronic toxoplasmosis and PBMC from 10 seronegative healthy controls did not secrete Toxoplasma-specific antibodies. This in vitro antibody secretion was spontaneous, active and transient since it disappeared between 11 and 24 weeks after seroconversion. Anti-Toxoplasma antibody secretion by PBMC from patients with acute toxoplasmosis is consistent with an in vivo stimulation of the immune system by T. gondii antigens. Our results represent a new approach for studying the immunological response during T. gondii infection and could have important implications for the diagnosis of acute and re-activated toxoplasmosis. PMID- 1628422 TI - Comparison of the properties of the CsA analogs monoacetyl CyC (o-acetyl threonine2 cyclosporin) and methyl-alanyl CsA (N-methyl-L-alanyl6 cyclosporin); monoacetyl cyclosporin is immunosuppressive without binding to cyclophilin. AB - Cyclosporin (CsA) is an immunosuppressant which binds to cyclophilin (Cyp). The relationship between Cyp binding and immunosuppression has been questioned since one of the analogs of CsA, N-methyl-L-alanyl6 cyclosporin (methyl-alanyl CsA) binds to Cyp but is not immunosuppressive. We compared the immunosuppressive properties of CsA, methyl-alanyl CsA and o-acetyl-threonine2 cyclosporin (monoacetyl CyC), since monoacetyl CyC does not bind to Cyp when tested in cell free assays and its immunosuppressive properties had not been tested. Cyp is a peptidyl-prolyl isomerase which is abundant in all human tissues, yet the activities of CsA are mostly confined to inhibition of T cell and thymocyte activation, and to neuro- and nephro-toxicity and are independent of inhibition of the isomerase. Activation of thymocytes and of T cells is regulated by the binding of a nuclear factor(s) (NFs) to the NF-AT region (-285 to -255) of the IL 2 promoter. We studied inhibition of binding to the NF-AT region of NFs derived from primary cultures of thymocytes treated with CsA or its analogs. In addition, we compared the effect of CsA and its analogs on the expression of the IL-2 gene in a stably transfected Jurkat-cell line (Fgl 5) which contains three copies of NF-AT and the reporter enzyme beta-galactosidase; and on inhibition of proliferation induced by concanavalin A (Con A) or IL-2. We found that monoacetyl CyC which does not bind to Cyp is immunosuppressive by our criteria when tested in cultured cells due to either a different mechanism of action or to metabolic activation. PMID- 1628423 TI - Functionally active complement is present in human ovarian follicular fluid and can be activated by seminal plasma. AB - Human ovarian preovulatory follicular fluids (FF) from 10 women were analysed for their complement contents. Functionally active complement was detected in all the fluids studied in amounts similar to those present in normal human serum. Pooled FF was challenged by seminal plasma in order to determine whether seminal plasma could activate FF complement, the pattern of such an activation and the possible consequences on the reproductive function. FF complement activation occurred during the incubation with seminal plasma with features including alternative pathway activation, factor B and C3 conversion and reduction in total haemolytic complement, as well as an inhibition by seminal plasma of the FF complement response to a new activating challenge. Possible consequences for fertilization, implantation of a fertilized ovum and local defence mechanisms against viruses and bacteria are discussed. PMID- 1628424 TI - Abnormal production of B cell growth factor in patients with systemic lupus erythematosus. AB - In order to clarify the role of B cell growth factor (BCGF) in the pathogenesis of systemic lupus erythematosus (SLE), BCGF production by peripheral blood mononuclear cells (PBMC) and T cells was studied using a new bioassay for BCGF activity. For this purpose, we established an Epstein-Barr (EB) virus-transformed B cell line KS-3.F10 that proliferates only in response to two B cell-specific BCGF, low-mol. wt BCGF (LMW-BCGF) and high-mol. wt BCGF (HMW-BCGF). PBMC from active SLE patients produced less BCGF when stimulated with phytohaemagglutinin (PHA) compared with controls. The decreased BCGF production by PHA-stimulated PBMC from active SLE reverted to control values when SLE became inactive. However, PHA-stimulated T cells from active SLE patients produced more BCGF compared with controls, whereas those from inactive SLE showed normal BCGF production. Spontaneous BCGF production by T cells was not observed in active SLE patients. These findings suggest that decreased BCGF production by SLE PBMC is due to excessive BCGF consumption by B cells in vitro and that SLE T cells produce large amounts of BCGF with appropriate immune stimuli in vivo to promote polyclonal B cell activation. PMID- 1628425 TI - Expression of antigen reactive with a monoclonal antibody to HTLV-1 P19 in salivary glands in Sjogren's syndrome. AB - To examine the possible involvement of retroviruses in Sjogren's syndrome (SS), labial salivary gland sections from 99 individuals were probed with three MoAbs to core (gag) proteins of human T cell leukaemia virus-1 (HTLV-1) and two MoAbs to HIV-1. Sections from 31% of 39 patients with primary SS (pSS) contained an epithelial cytoplasmic protein reactive with a MoAb (197) to the p19 group specific antigen (gag) of HTLV-1. The antigen was also detected in samples from 24% of 17 patients with rheumatoid arthritis (RA) and SS, 21% of 14 patients with sicca symptoms and 12.5% of 16 patients with other connective tissue diseases. It was not found in the salivary glands of 13 normal controls. A second MoAb to p19 gag, a MoAb to the p24 gag of HTLV-1 and MoAbs to HIV-1 p17 and p24 gags gave negative reactions. Serum antibodies to HTLV-1 were negative, confirming that the antigen was not part of HTLV-1. The antigen showed properties consistent with an endogenous retrovirus in that it was absent in healthy tissues or resting cells but inducible by stimulation with phytohaemagglutinin (PHA) or interferon-gamma (IFN-gamma). It appeared to be distinct from the endogenous retroviral sequence HRES-1. These data suggest the presence of an endogenous retrovirus in salivary gland epithelium which could contribute to the chronic inflammation of SS. PMID- 1628426 TI - Reassessment of the relative prevalences of antibodies to gastric parietal cell and to intrinsic factor in patients with pernicious anaemia: influence of patient age and race. AB - Anti-parietal cell antibody has been reported in nearly all patients with pernicious anaemia in past studies, in contrast with anti-intrinsic factor (IF) antibody which occurs in only 50-70% of such patients. However, observations in the more diverse patient population at our hospital suggest that these prevalences, originally described in predominantly elderly, white patients of European origin, no longer apply. Anti-IF antibody was found in 70% of the 324 patients, with blacks (84%) and Latin Americans (69%) having a significantly higher prevalence than whites (55%). In contrast, only 55% of the 266 patients tested had anti-parietal cell antibody. It was noteworthy that this low rate was similar in all racial groups. However, patients lacking anti-parietal cell antibody were significantly younger than those who had the antibody (54.8 +/- 17.8 vs 59.6 +/- 16.2 years, P = 0.022). Overall, a striking 30% of all patients had anti-IF antibody but not anti-parietal cell antibody, while only 13% had the latter antibody without having anti-IF antibody. This pattern was particularly striking among black patients. An interesting incidental observation was that gastrin levels were not associated with antibody status, but were significantly higher not only among women than among men but also among white and black patients than among Latin-American patients. The findings show that anti-parietal cell antibody is not found nearly as often in pernicious anaemia as has been reported in the past, and thus has no value as a diagnostic tool in pernicious anaemia. They also suggest clues to different expressions of pernicious anaemia or of its immunologic response, particularly among younger patients with the disease. PMID- 1628427 TI - T lymphocyte anergy during acute infectious mononucleosis is restricted to the clonotypic receptor activation pathway. AB - The transient T cell anergy associated with acute infectious mononucleosis (IM) caused by the Epstein-Barr virus has been analysed in a sample of 14 IM children. Peripheral blood mononuclear cells (PBMC) obtained from IM patients showed a significant specific impairment in their proliferative response to both phytohaemagglutinin (PHA; P less than 0.05) and to an anti-CD3 MoAb (P less than 0.001), although both responses reached normal control levels by addition of a submitogenic dose of either phorbol myristate acetate (PMA) or recombinant IL-2 (rIL-2). In contrast, activation signals delivered through other surface molecules (CD2, CD28) or other transmembrane pathways (PMA plus a calcium ionophore) elicited normal or high proliferative responses in most IM PBMC. In a group of five patients tested, the synthesis of IL-2 by IM PBMC in the presence of PMA was impaired when PHA or anti-CD3 was used as stimulus, but it reached normal levels with anti-CD2 or ionophore. Lastly, PHA failed to induce IL-2 alpha receptor (IL-2R alpha) expression in IM PBMC from four tested patients, but the presence of PMA completely corrected this defect. Taken together, these results strongly suggest that the T cell anergy associated with acute IM is due to a T cell receptor (TCR)-specific impairment in the induction of genes involved in T cell proliferation (including those coding for IL-2 and IL-2R alpha) upon membrane signalling to otherwise normal T lymphocytes, since CD2, CD28 and certain transmembrane activation pathways are uncoupled from CD3 in these particular pathological conditions (and perhaps in most in vivo situations). This and other similar experimental approaches to transient secondary immunodeficiencies may help to unravel the physiopathological role of different surface molecules in T cell activation. PMID- 1628428 TI - Distribution of retroviral p15E-related proteins in neoplastic and non-neoplastic human tissues, and their role in the regulation of the immune response. AB - In patients with head and neck carcinomas and in patients with chronic purulent upper airway infections, low molecular weight retroviral p15E-like factors are found. These factors are responsible for partial defects in the cellular immune response. We studied the distribution of these p15E-related proteins in neoplastic, inflamed and normal human tissues and related these findings with the presence of p15E-like factors in patients' sera. Demonstration of p15E-like proteins in sera of patients with upper airway infections and of patients with head and neck carcinomas correlated exclusively with the presence of p15E in normal and pathologic epithelium of the upper respiratory tract. p15E was not demonstrated in epithelia of other localizations. Our results suggest that chronic stimulation or neoplastic transformation of the epithelia of the upper respiratory tract stimulates the production of p15E-like proteins leading to their reported immunosuppressive actions. PMID- 1628429 TI - IVth European Meeting of Neuropathology. Berlin, July 14-18, 1992. Abstracts. PMID- 1628430 TI - [Analysis of cognitive function and regional cerebral blood flow in Parkinson's disease by 123I-IMP SPECT]. AB - To investigate the relationship between the alterations of regional cerebral blood flow (rCBF) and the cognitive impairment in parkinsonian patients, I studied forty-one patients affected by Parkinson's disease (19 men and 22 women) using single photon emission computed tomography (SPECT) and N-isopropyl-p-[123I] iodoamphetamine (123I-IMP) as a tracer. I evaluated the cognitive function with the Mini-Mental State examination (MMS), the Hasegawa's Dementia Scale (HDS), the Kana-pick up test (KT), and the figure drawing test (FDT). I evaluated the motor impairment with the Hoehn and Yahr stage. SPECT scanning was performed with a rotating digital gamma camera TOSHIBA 901-A. A semiquantitative method of assessing regional tracer uptake was used. Regions of interest (ROI; 3 x 3 pixels, 15.9 x 15.9 mm2) were drawn on the cerebellar hemispheres, cortical regions (frontal, temporal, parietal and occipital), and basal ganglia bilaterally. The RI count index was expressed as a ratio of activity in each ROI to mean counting rate over cerebellar regions. I considered the RI count index as the index of rCBF in each ROI. There were strong positive correlations between MMS and rCBF of frontal, parietal and occipital lobes (p less than 0.001). There were positive correlations between HDS and rCBF of frontal (p less than 0.01), parietal (p less than 0.001) and occipital lobes (p less than 0.01). There were positive correlations between KT and rCBF of frontal (p less than 0.01), occipital (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628431 TI - [Linkage study of Machado-Joseph disease: genetic evidence for the locus different from SCA1]. AB - Spinocerebellar ataxia 1 (SCA1) is the locus symbol of hereditary olivopontocerebellar atrophy, and it is mapped on the short arm of chromosome 6. D6S89 is the polymorphic DNA marker linked tightly to SCA1. In order to examine whether SCA1 and Machado-Joseph disease (MJD) loci are different from each other, we performed linkage study for D6S89 to MJD locus. A total of 20 pedigrees of MJD were analysed. Number of individuals consists of 211 members. Among them, 74 were affected. Consequently, 14 pedigrees showed negative lod score, and 6 showed weak positive lod scores at most of recombination fractions. As a whole, linkage between MJD locus and D6S89 was excluded at recombination fraction of 0.15. Our results further support the concept that MJD is not an allelic disorder but distinct genetic entity from SCA1. PMID- 1628432 TI - [Linkage study of hereditary olivopontocerebellar atrophy: genetic evidence for locus heterogeneity in Japanese cases]. AB - Spinocerebellar ataxial 1 (SCA1) is the locus name of autosomal dominant olivopontocerebellar atrophy (OPCA), and is assigned to the short arm of chromosome 6. The tight linkage between SCA1 and D6S89 has recently been reported. In order to examine possible locus heterogeneity, we studied linkage for D6S89 to disease loci in 16 pedigrees of dominant OPCA. D6S89 polymorphism was analysed with PCR amplification of genomic DNA by using specific oligonucleotide primers. Lod scores were computed by LIPED program with the correction of age-dependent penetrance. Homogeneity test was performed by using HOMOG program. Fifteen out of 16 pedigrees were informative to D6S89. Among them, 7 pedigrees showed positive and 8 pedigrees showed negative lod scores throughout all recombination fractions. Homogeneity testing disclosed that approximately 55% of pedigrees are linked to D6S89, and others were not linked. Our results provide evidences that dominant OPCA in Japan are genetically heterogenous. At now, it has been still unknown whether there are any clinico-pathological differences among OPCA genotypes. Based on the alpha-constant from homogeneity testing, we divided our pedigrees into linked-pedigree (SCA1) and nonlinked-pedigrees (nonSCA1). Then, clinical features were compared between these two groups. Hyperactive DTR was more common in SCA1 than nonSCA1 group. On the other hand, hypoactive DTR was more significantly dominated in nonSCA1 than SCA1. Slow saccade and Babinski sign were common in both groups. Although not statistically significant, nystagmus, exteral ophthalmoparesis, mydriasis, ptosis, facio lingual twitching, and limb spasticity were more frequently observed in SCA1 than nonSCA1. These results indicate that there are possible correlation between disease genotype and phenotype.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628433 TI - [An autopsy case of Degos disease with neurological symptoms--neuropathological observations and increased platelet aggregation]. AB - We reported clinical and neuropathological observations of a 41-year-old man with Degos disease. He first noted painless skin lesions over the upper extremities in January, 1982. Three years later he was diagnosed as Degos disease by skin biopsy, and treatment with aspirin was started. In September, 1985, he complained of paresthesia on his right arm, followed by a series of new neurological manifestations suggesting multifocal spinal cord lesions. On October 28, examination of admission showed papules with central umblication over the whole body except the head, face, palms, soles and scrotum. Neurological examination revealed no weakness, diminished right biceps reflex, exaggerated patellar reflexes and Achilles reflexes, left extensor plantar reflex, hypesthesia and hypalgesia to the level of Th8, mild left spastic gait, and retention of urine. In November, he had paraparesis, loss of vibration sense of lower extremities, hypesthesia and hypalgesia to the level of TH4, and weakness of right upper extremity. In December, he showed tetraplegia, left-sided facial palsy, and hypesthesia and hypalgesia to the level of C5. In January, 1986, he showed right facial palsy, left facial hypesthesia, pseudobulbar palsy. In February, he had bilateral abducens nerve palsy and hiccups. On February 18, he died of intracranial hemorrhages. He had episodic abdominal pain several times during admission. His condition deteriorated progressively in four months after the first manifestation of neurological symptoms, despite the therapy with heparin, urokinase, ticlopidine, dipyridamole, and prednisolone. Laboratory studies showed gradual increase of CSF proteins (from 156 mg/dl to 602 mg/dl) and extremely increased platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628434 TI - ["Dynamic" MR imaging of the cervical cord in patients with cervical spondylosis and ossification of the posterior longitudinal ligament--significance of dynamic cord compression]. AB - This investigation was designed to assess the influence of dynamic cord compression on severity and course of myelopathy. Sixty-seven patients studied comprised 54 cases of cervical spondylosis and 13 cases of ossification of the posterior longitudinal ligament. These patients underwent "dynamic" MR imaging of the cervical spine. MR images in the sagittal view were obtained in three different neck positions: flexion, neutral, and extension. MR imaging was performed with a 0.15 T resistive unit. For technical reasons, the body coil was used. The pulse sequence was 500/30 (Tr msec/echo time msec) for T1 images. The spinal cord compression was accelerated in 32 cases when extended, in 2 cases when flexed, and in 4 cases when both extended and flexed. In 21 cases, we compared myelograms with MR images in a same neck position. Findings of myelograms well corresponded with those of MR images on 83 percent of intervertebral levels. The patients with dynamic cord compression were proved to have severer long tract signs, and their disability was regressive or progressive case by case for an average of 21-month follow-up. The "dynamic" MR imaging can provide dynamic nature of spinal cord compression, and prognostic clues. PMID- 1628435 TI - [A case of chronic progressive external ophthalmoplegia associated with familial hypercholesterolemia]. AB - A 52-year-old woman with chronic progressive external ophthalmoplegia (CPEO) with familial hypercholesterolemia (FH) was reported. Her mother died from heart disease, and her elder sister has hypercholesterolemia with swelling of Achilles tendons. She had slowly progressive external ophthalmoplegia, bilateral ptosis, swelling of Achilles tendons since twenties. At 40 years of age, she was pointed out hypercholesterolemia. Physical examination was within normal limits except for bilateral swelling of Achilles tendons. Neurological findings showed bilateral ptosis, disturbance of eye movements, mild proximal muscle weakness and dysesthesia in bilateral hands. Routine laboratory findings were within normal limits except for high serum cholesterol level (512 mg/dl). In the biopsied muscle, there was mild variation in fiber size with several ragged-red fibers and focal cytochrome c oxidase defective fibers. Biochemical analysis of the biopsied muscle revealed normal values in the mitochondrial fraction. Southern blot analysis of the mitochondrial DNA (mtDNA) of the muscle disclosed mixed population of mtDNA, consisting of the normal one and partially deleted (4.9 kilobase). Southern blot analysis of the leukocytes from the patient against the cDNA of LDL receptor was normal at least using the restriction enzyme of BglII, XbaI, EcoRI, PvuII and BamHI. This case has CPEO with deleted mtDNA associated with familial hypercholesterolemia, which is caused to nuclear DNA abnormalities, and is thought to be an important case for us to study the relationship between deleted mtDNA and abnormal nuclear DNA in CPEO. PMID- 1628436 TI - [A case of multiple sclerosis with paroxysmal attacks of facial paresthesia, unilateral hand tremor, epigastric pain and urinary incontinence]. AB - A Japanese woman, aged 42, was admitted because of paroxysmal attacks consisting of paresthesia of the left face, tremor in the right hand, epigastric pain and urinary incontinence. A year prior to the admission, she noticed some difficulty in writing, dysarthria and unsteadiness of walking. These symptoms had been persistent since then. At the end of March, 1991, these symptoms rapidly worsened, and she fell down frequently. She also experienced pain behind both eyes, numbness in her left fingers and toe, urinary frequency and the above mentioned attacks. Neurological examination disclosed bilateral internuclear ophthalmoplegia and upbeating nystagmus on upward gaze, titubation in the head, scanning speech, dysmetria in all limbs, exaggerated reflexes in jaw and both legs, bilateral extensor plantar reflexes and ankle clonus. SEP showed delayed cortical response with stimulation of the median nerves bilaterally and of the right posterior tibial nerve. P40 was absent with the left posterior tibial nerve stimulation. VEP was normal. T2-weighted image of MRI showed multiple high intensity areas located around the third ventricle, crus cerebri and the right upper part of the pons. The diagnosis of multiple sclerosis was made. Each paroxysmal attack started with numbness in the left face and burning sensation in the neck. Almost simultaneously tremor in the right hand began. The surface EMG showed the rhythmic contractions in the dorsal hand muscles and wrist extensors at a frequency of 6-7 Hz, and sometimes it revealed synchronized contractions of finger flexors and the dorsal hand muscles. A few seconds later she felt painful sensation in the epigastric region, and the tremor gradually increased in its intensity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628437 TI - [A case of motor neuron disease with dementia--cerebral blood flow and cerebral oxygen metabolism]. AB - A 51-year-old man developed muscle weakness of the bilateral upper extremities, and mental changes beginning with personality change. There was no history of mental illness in his family. A neurological examination 1 year after the onset revealed muscle atrophy and fasciculation of his bilateral upper extremities Neuropsychological examination revealed concrete speech, paraphasia, and lack of judgment. Disorientation, amnesia, dyscalculia, and spatial agnosia, however, were not recognized. These neuropsychological findings were compatible with dementia of frontal lobe type. EMG and muscle biopsy revealed neurogenic muscular atrophy. There was no abnormal findings in the brain X-CT and the brain MRI. PET study using C15O2 and 15O2 revealed reduction of cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) in the bilateral medial frontal cortex, the left temporal cortex and the bilateral thalamus. From these these findings the patient was diagnosed as having motor neuron disease with dementia. Muscle atrophy and dementia worsened gradually. A second PET study 2 years and 6 months after the onset revealed severe reduction of CBF and CMRO2 in the bilateral temporal cortex and the thalamus. These PET findings suggested that dysfunction of the temporal cortex and the thalamus related to dementia in this case. PMID- 1628438 TI - [Central diabetes insipidus complicated with upbeat nystagmus and cerebellar ataxia]. AB - A 34-year-old male presented with central diabetes insipidus accompanied by upbeat nystagmus and cerebellar ataxia. The patient without family history of above began to walk at the age of 2 years. Polyposia and polyuria were noted at the age of about 4 years. Dysbasia developed at the age of about 7 years. From the age of 30, lalopathy appeared together with various clinical symptoms including cataracts, disturbed intelligence, upbeat nystagmus, abnormal ocular movements, ataxic speech, cerebellar ataxia and reduction of the muscle tone of the limbs, and hypotonic polyuria. Abnormal laboratory findings included square wave jerks, upbeat nystagmus, and "bow tie" nystagmus by EOG, atrophy of the cerebellum and the brainstem by CT, a slight prolongation of the P300 latency, and a central diabetes insipidus pattern by water deprivation test and Carter Robbins tests. There have been occasional reports of diabetes insipidus complicated by cerebellar ataxia, but in no earlier reports has diabetes insipidus been concurrent with abnormal ocular movements such as upbeat nystagmus. A degenerative disease primarily of the posterior lobe of the hypophysis, hypothalamus, cerebellum, and brainstem was suspected. PMID- 1628439 TI - [Hemiplegic migraine complicated with coronary vasospasm]. AB - There are many theories and hypotheses concerning with the pathogenesis of migraine. The clinical effectiveness of vasoactive drugs and many investigations on the cerebral blood flow in patients with migraine strongly support a vascular theory. In present paper we report a case of 26-year-old Japanese male, who suffered from hemiplegic migraine and coincidental coronary vasospasm, and discussed the pathogenesis of migraine. In October 1986, the patient developed the first attack of throbbing headache in the left temporal area with nausea and vomiting, following typical visual aura. One week later, he developed the second migrainous attack and then he felt his right extremities paralyzed and numb. Although the headache and weakness resolved within one hour, similar migrainous attack with transient hemiparesis repeated two or three times a month. Although the longest period required for resolving weakness was three days, the MRI, the CT and the electroencephalogram revealed no significant abnormality. In January 1987, during his stereotyped attack of hemiplegic migraine, he also developed oppressive feeling on his anterior chest and these symptoms resolved within fifteen minutes. Because the results of Holter electrocardiogram and ultrasound echocardiogram indicated angina pectoris, a coronary angiography was performed in February 1987. During the angiographical procedures, he began to complain of the oppressive feeling on his anterior chest, and the coronary angiography revealed the definite vasospasm in the anterior descending branch of the left coronary artery. Sublingual nitroglycerin administration resolved the vasospasm, but thereafter the patient developed his stereotyped hemiplegic migrainous attack.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628440 TI - [Rapid spontaneous postpartum remission in a case of chronic inflammatory demyelinating polyradiculoneuropathy associated with pregnancy]. AB - A 28-year-old woman developed numbness and weakness of the hands and arms when she was 8 months pregnant, and weakness worsened gradually. However, weakness started to spontaneously subside immediately after delivery and she felt almost recovered several hours later. But weakness and numbness recurred one week after delivery and she was admitted to our hospital. Neurological examination revealed moderate weakness and disturbance of the deep and cutaneous sensations in the upper and lower extremities, and marked decrease of the deep tendon reflexes. The upper extremities were more severely affected. Nerve conduction study showed marked decrease in the motor conduction velocities. Cerebrospinal fluid showed increase of protein without pleocytosis. Teased preparation of the biopsied sural nerve showed occasional internodal segments with thin myelination, indicating demyelination and remyelination. A diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy was made. Treatment with prednisolone markedly improved the weakness and hyporeflexia as well as the cerebrospinal fluid protein. Postpartum rapid remission may have been produced by rapid increase of endogenous steroid hormone in the blood by its massive excretion during delivery. PMID- 1628441 TI - [Magnetic resonance imaging in Parkinson's disease--the evaluation of the width of pars compacta on T2 weighted image]. AB - The width of substantia nigra (SN) in 59 cases with idiopathic Parkinson's disease as well as 21 normal controls was analyzed by T2 weighted image (T2WI) of 1.5 Tesla high-field magnetic resonance image (MRI). All patients and controls underwent MRI with the spin-echo sequences used TR/TE: 3000/30 (short TE), and TR/TE:3000/80 (long TE), in 5-mm-thick volumes. The width between the red nucleus and the cerebral peduncle showing low signal intensity areas was measured as that of SN and its ratio to the distance from the aqueduct to the midline of the cerebral peduncle was also measured. The calculated values of the width of SN and its ratio were analyzed by Mann-Whitney test. The significant reduction in the width of SN and its ratio in Parkinson's disease were disclosed as below; the mean calculated values of the width of SN were 2.95 +/- 0.51 mm in controls, 2.68 +/- 0.99 mm in Parkinson's diseases on long TE images (P less than 0.01), and the mean ratio of the width of SN were 13.58 +/- 4.21% in controls, 10.52 +/- 3.07% in Parkinson's diseases on long TE images (P = 0.0002). The narrowing of SN in Parkinson's disease was more prominent in men, and advanced cases with Yahr stage III and IV. Considering that the pars reticulata, which is normally containing iron, shows low signal intensity on long TE images, the width of pars compacta could be measured more precisely on this sequences. The evaluation of the ratio of SN in midbrain on long TE images seemed to be more sensitive than the calculated values in detecting the narrowing of SN and pars compacta in Parkinson's disease. PMID- 1628442 TI - [XYY syndrome associated with motor neuropathy]. AB - We described a case of XYY syndrome associated with motor neuropathy. The case was a 27-year-old male, who had 47-XYY chromosome karyotype. His symptoms were distal dominant muscle weakness and muscle atrophy in his lower extremities without objective sensory disturbance. He had no mental retardation or family history of neurologic diseases. The electrophysiological and pathological examinations revealed that his symptoms were due to peripheral motor neuropathy (neuronal type). His motor neuropathy may be of sporadic type. There may be some relation in the pathogenesis between XYY syndrome and motor neuropathy, although in the literature, XYY syndrome with motor neuropathy had not been reported so far. PMID- 1628443 TI - [A case of chronic toluene intoxication with abnormal MRI findings: abnormal intensity areas in cerebral white matter, basal ganglia, internal capsule, brain stem and middle cerebellar peduncle]. AB - We reported a case of 21 years old man of chronic toluene intoxication with abnormal intensity areas on MRI in cerebral white matter, basal ganglia, internal capsule (especially posterior limb), brain stem and middle cerebellar peduncle. The patient developed various neurological abnormalities such as blurred vision, ataxic speech, gaze evoked horizontal nystagmus, bilateral pyramidal tract sign and limb ataxia after 8 years sniffing of thinner (mainly toluene). MRI examination revealed diffuse high intensity areas in cerebral white matter on T1 weighted image. On T2 weighted image, high intensity areas of deep cerebral white matter, internal capsule (especially posterior limb), cerebral peduncle, ventral pons and middle cerebellar peduncle were noted. Basal ganglia (caudate nucleus, lenticular nucleus and thalamus) were displayed as low intensity area on T2 weighted image. These high intensity areas of internal capsule, brain stem and middle cerebellar peduncle on T2 weighted image would be significant for understanding pyramidal tract sign and cerebellar sign of this case. On the basis of neuropathological descriptions of chronic toluene intoxication, these high intensity areas of T2 weighted image were presumed to be demyelinating lesions of the central nervous system. PMID- 1628444 TI - [Rapid diagnosis of tuberculous meningitis by polymerase chain reaction (PCR)]. AB - Using polymerase chain reaction (PCR), a rapid and highly sensitive method was developed for the diagnosis of tuberculous meningitis. The mycobacterium tuberculosis (M. tuberculosis) genome was detected in CSF of 5 of 6 patients with clinically diagnosed tuberculous meningitis, but not present in CSF from 10 patients with other types of meningitis and 10 normal controls. Furthermore, we detected M. tuberculosis in CSF of 2 of 24 patients with clinically possible tuberculous meningitis. This is highly useful method for the rapid diagnosis of tuberculous meningitis over other conventional method. PMID- 1628445 TI - [Paradoxical expansion of intracranial tuberculomas during chemotherapy]. AB - A 45-year-old female patient was admitted to a hospital because of tuberculous meningitis in July, 1986. She was treated with chemotherapy (oral isoniazid, rifampicin, ethambutol and an intramuscular injection of streptomycin). Her consciousness was worsened at first, but later she improved aside from some disabilities (incontinence, gait disturbance, disorientation and dementia). She was transferred to National Higashisaitama Hospital in November, 1986. Since then we have continued the chemotherapy, and she has improved gradually. Initially her cranial computerized tomography (CT) revealed no intracranial tuberculoma and showed mild enhancement of basal cistern. About 4 months later, her CT showed many tuberculomas with ringed or nodular enhancement. About 13 months later almost all tuberculomas disappeared. But a few were found with homogeneous enhancement and were enlarged in spite of adequate chemotherapy. These tuberculomas were enlarged while the chemotherapy was continued, but later they were reduced in size. About 3 and a half years later, these tuberculomas disappeared without any calcifications. The above facts may suggest that intracranial tuberculoma could appear and be enlarged on cranial CT in spite of adequate chemotherapy during a course of tuberculous meningitis. They also suggest that continuation of adequate chemotherapy might improve tuberculomas. PMID- 1628446 TI - [Some questions and comments for the original article entitled "autosomal recessive oculopharyngeal 'muscular dystrophy'"]. PMID- 1628447 TI - [A quantitative analysis of ataxia in the upper limbs]. AB - By using a transparent digitizer and a personal computer, we tried a quantitative analysis of ataxia in the upper limbs. A total of 25 upper extremities of 13 patients with spino-cerebellar degeneration (SCD) and 140 upper extremities of 70 normal volunteers were tested by two types of tasks. One was the free speed trace of a circle presented on the display (free circle), and the other was the pursuit of a target moving on a circle at a fixed speed (pursuit circle). The digitizer was put on a color display stabilized horizontally. For 1024 points with a 25 msec sampling time, the trajectory of the stylus pen was transmitted to the computer in real time. Circle diameters of 3 cm and 6 cm were selected. The target rounded the circle at a speed of 6 or 3 times per 1024 points. The mean velocity (MV), mean acceleration (MA), and MA/MV ratio were calculated for the extent of one circle period. And the coefficient of variation (CV) of the shifted distance in each sampling time and the power spectrum by Fast Fourier Transform (FFT) to the acceleration wave were calculated for the total input data. In the free circles, the MV and logarithm of MA varied widely and showed positive correlations. In contrast, those of the pursuit circles converged narrowly near the values of the target. On the other hand, in the SCD group, many patients could not draw the small free circle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628448 TI - [A clinicopathological study of two respirator-aided long-survival cases of amyotrophic lateral sclerosis]. AB - We reported two respirator-aided 10-year-survival male patients with sporadic amyotrophic lateral sclerosis (ALS). Their ages at onset were 54 and 52, clinical features common in both cases, the durations to tracheotomy 32 months and 27 months respectively, and the durations for respiratory support over 8 years in both cases. There were normal external ocular movement, normal pelvic sphincter function, normal sensory system and no bed sores throughout 10 years of illness. The brain weighted 1,295 g in case 1 and 1,430 g in case 2, being normal macroscopically. The spinal cord was slightly wasted with atrophic anterior roots. The histopathological study demonstrated the typical pattern of ALS in spite of the prolonged survival with artificial respiration. Neuronal loss and gliosis of the motor nuclei in the spinal cord and brainstem were more striking than those of the natural course. Neither hypertrophic astrocyte, central chromatolysis nor neuronophagia was observed. This finding suggested inactive condition of the degeneration. The pattern of white matter degeneration in the cord indicated some pallor of anterior and lateral columns, severe pallor of pyramidal tracts and intact posterior column and spinocerebellar tracts. The giant pyramidal cells in the precentral gyrus were lost in both cases. Pyramidal degeneration was traceable up to the cerebral peduncles in the case 2 and undetectable in that portion in the case 1. On the other hand, the extraocular muscle nuclei, the Onuf's nuclei, the dorsal motor nucleus of the vagus nerve, intermediolateral and Clarke's nuclei were relatively preserved, though no cell count was done in Clarke's nuclei and Onuf's nuclei.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628449 TI - [CSF acetylcholinesterase activity in central neurological diseases involving cholinergic systems]. AB - The enzymatic activity of acetylcholinesterase (AchE) in the cerebrospinal fluid (CSF) is considered to be a marker of central cholinergic neuron integrity. Then, we evaluated CSF AchE activity in 90 cases of neurological diseases involving cholinergic system and their related disease, and 28 control cases without central organic lesions or abnormal findings in routine CSF study. AchE activity was evaluated according to Ellman's method using acetylthiocholine iodide as a substrate and tetraisopropyl-pyrophosphoramide, a specific inhibitor of butyrylocholinesterase. CSF AchE of Alzheimer type dementia (AD/SDAT, N = 12: 21.9 +/- 4.7 nmol/ml/min) showed no significant change from those of both control group (22.1 +/- 3.9) and vascular dementia (9: 21.7 +/- 6.7). In extrapyramidal diseases, reduction of the activity was observed in Huntington's chorea (HC, 4: 16.3 +/- 1.4) and progressive supranuclear palsy (PSP, 4: 17.6 +/- 1.7), whereas normal activity was shown in Parkinson's disease (PD, 19: 22.5 +/- 4.6), dentatorubropallidoluysian atrophy (DRPLA, 4: 22.6 +/- 4.2) and striatonigral degeneration (SND, 4: 20.4 +/- 4.3). In olivopontocerebellar atrophy (OPCA, N = 16), we disclosed reduced CSF AchE activity (15.8 +/- 2.4) which had significant correlations with the atrophy of the pontine base (r = 0.6017, p less than 0.02) and cerebellar vermis (r = 0.5450, p less than 0.05) in MRI. AchE activity in cerebellar cortical atrophy (CCA, 5: 20.6 +/- 2.2) remained within the control values. Normal activity was demonstrated in both amyotrophic lateral sclerosis (6: 24.3 +/- 7.3) and spinal muscular atrophy (4: 22.9 +/- 3.9).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628450 TI - [Cytokine production by peripheral blood monocytes/macrophages in the patients with multiple sclerosis and its suppression by methylprednisolone]. AB - The production of tumor necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) by stimulated peripheral blood monocytes/macrophages (PBM) was assessed in patients with multiple sclerosis (MS), other neurological diseases (OND) or normal controls (NC) using enzyme-linked immunosorbent assay (ELISA). PBM obtained from acute phase of MS produced significantly higher amount of all these cytokines than those from chronic stable MS, OND or NC (TNF alpha, IL-1 alpha, IL-6: p less than 0.01, IL-1 beta: p less than 0.05). Methylprednisolone (MP) inhibited the lipopolysaccharide-induced cytokine production in a dose-dependent manner. These results suggest the possible roles of activated monocytes/macrophages in the acute exacervation of MS and suppressive effect of MP on cytokine production by activated monocytes/macrophages. PMID- 1628451 TI - [Effects of insulin-induced hypoglycemia on catecholamine secretion and blood pressure in neurological disorders affecting autonomic nervous system]. AB - The effects of insulin-induced hypoglycemia on catecholamine secretion were investigated in patients with various neurological disorders affecting the autonomic nervous system. In control subjects, insulin-induced hypoglycemia resulted in marked increases in plasma epinephrine and norepinephrine levels. Heart rates were increased within 15 minutes after the insulin injection which were associated with slight elevation and depression of systolic and diastolic blood pressure, respectively. In patients with upper level spinal cord lesions (C1-T6) of various etiology, Shy-Drager syndrome and familial amyloidosis, insulin-induced hypoglycemia failed to increase plasma epinephrine and norepinephrine levels and resulted in falls in systolic and/or diastolic blood pressure 15 minutes after the injection. Heart rates were increased at 30-45 minutes after the injection. In patients with lower spinal cord lesions (T10-L1), neurosyphilis or brain stem tumor with orthostatic hypotension, the catecholamine responses were normal and blood pressure did not fall during insulin-induced hypoglycemia. In patients with Parkinson's disease and spinocerebellar degeneration with autonomic symptoms catecholamine responses were not impaired. These findings suggest that any lesion involving the sympathetic efferent systems of baroreflex such as the spinal descending pathway, sympathetic preganglionic neuron and peripheral nervous system causes both impairment of catecholamine secretion and a fall in blood pressure during hypoglycemia, and that lesions in sympatho-afferent system may not affect the secretion of catecholamine and neural control of blood pressure. PMID- 1628452 TI - [A case report of cerebral achromatopsia with bilateral occipital lesion]. AB - An 80-year-old right-handed man suddenly became impossible to recognize any color 7 years prior to admission. He complained that everything looked like of the same color, monochromatic. On admission, he could not discriminate any color and any familial face. Left homonymous hemianopsia associated with right lower partial visual filed defect was observed, but visual acuity of both eyes was well preserved. Visual-visual color tasks (Ishihara, matching, Hue test, Panel-D15) disclosed the disturbances in color perception. However, he could roughly distinguished red or brown from the other colors. The color test was also impaired regarding the visual-verbal color tasks (naming, pointing). However, verbal description of the color concept, which was shown by the verbal-verbal color tasks, was well preserved. In addition, we observed left hemispatial neglect, disturbance of face recognition and topographical disorientation. MRI revealed old hemorrhagic infarcts in the bilateral occipital and temporal lobes, including the bilateral lateral and medial occipito-temporal gyri. Disturbance of color recognition in this case was diagnosed as cerebral achromatopsia on the basis of clinical characteristics and MRI findings. This is the first case of cerebral achromatopsia of which lesions were detected by MRI in detail. PMID- 1628453 TI - [An acute axonal polyneuropathy affecting intrinsic hand muscles following Campylobacter infection--a case report]. AB - A 24-year-old carpenter had the shakes and fever on March 13, 1990. He suffered from watery diarrhea on March 14 and 15. He left muscle weakness in his thumbs and fingers when he drove nails with a hammer on March 24. The weakness reached maximum by the 3rd day of illness. He was admitted to our hospital on day 4. Neurological examination revealed symmetrical weakness localized in the intrinsic hand muscles (MRC grade 2-4). The deep tendon reflexes were preserved. Sensation was intact except for mild disturbance of superficial sense on both plantar areas. Campylobacter jejuni was cultured from his stool. A complement fixation test indicated serologically preceding C. jejuni infection. Whereas maximum motor nerve conduction velocities were not reduced and distal latencies were not prolonged, compound muscle action potential recorded in the thenar and hypothenar muscles were remarkably reduced on day 5. Needle EMG showed neuropathic changes in four limbs. Sensory nerve conduction velocities and action potentials were normal. The weakness gradually improved in association with increased compound muscle action potentials in the thenar and hypothenar muscles. His muscle symptom fully resolved 2 months after the onset of his illness. Thin-layer chromatogram with immunostaining revealed that serum IgG from this patient reacted with GM1, GD1a, GD1b, but did not react with GM2 and GT1b. Enzyme-linked immunosorbent assay showed that anti-GM1, GD1a, GD1b antibodies titer (IgG) decreased concurrently with the clinical improvement. PMID- 1628454 TI - [A case of paraneoplastic cerebellar degeneration--success in early detection of cancer by anti-Purkinje cell antibody]. AB - A 70-year-old woman was admitted to our hospital because of rapidly progressive cerebellar ataxia. Neurological examinations showed saccadic eye movement, downbeat nystagmus, scanning speech, proximal dominant muscle weakness and severe truncal and limb ataxia. Based on these clinical features, she was suspected to have paraneoplastic cerebellar degeneration (PCD), although the malignant tumor was not detected through clinical intensive surveys. Her serum and CSF revealed to have anti-Purkinje cell antibodies immunohistochemically, and western blot analysis showed that they reacted with 58 kd band. In view of previous reports of PCD, she was strongly suspected to have gynecological cancers. The trial laparotomy found early stage fallopian tubal cancer, which had not been detected by CT scan, ultrasonogram and MRI. It is important to detect and characterize these autoantibodies found in the PCD patients for early diagnosis and treatment of underlying cancer. PMID- 1628455 TI - [A case of herpes zoster associated with multiple cranial nerve involvement]. AB - A 74-year-old man who had suffered from right herpes zoster ophthalmicus developed ipsilateral multiple cranial nerve involvement two weeks later. He showed right visual disturbance, total ophthalmoplegia and peripheral facial palsy. Pleocytosis and increased protein were found in CSF. Titer of VZV antibody increased in serum and CSF. CT and MRI demonstrated no abnormal findings in the brain stem. Within a month, peripheral facial palsy improved. Severe extra ophthalmoplegia began to improve after three months, and moderately recovered. After two and a half year, visual disturbance and mydriasis showed no improvement. In this case, we speculate that localized leptomeningitis caused multiple cranial nerve involvement. PMID- 1628456 TI - [Quantitative evaluation of tongue atrophy on midsagittal magnetic resonance images (MRIs)]. AB - This study was undertaken mainly to establish the quantitative parameter to evaluate the tongue atrophy on midsagittal MRIs and to show the clinical usefulness of such quantitative evaluation. Midsagittal MRIs of the tongue of consecutive 103 patients were analyzed. They were classified into 67 patients showing normal size (group without atrophy), 11 patients showing atrophy (group with atrophy) and 25 patients showing unsatisfactory MRIs with artefacts based on the routine evaluation. The patients in the group without atrophy did not show any pathologic processes to produce tongue atrophy on clinical findings. The area and perimeter of tongue and oral cavity, and the ratio of tongue area to oral cavity area and the ratio of tongue perimeter to oral cavity perimeter on midsagittal MRIs were obtained in each patient of groups with and without atrophy by using quantitative image analysis system. In the group without atrophy, regression analysis of the data on age was made and the 95% confidence interval of the data for age was obtained. No evidence that the tongue becomes atrophic with aging was obtained in the group without atrophy. Patients in the group with atrophy were best separated from those in the group without atrophy statistically when the ratio of tongue area to oral cavity area was regressed on age. Among 11 patients in the group with atrophy, 6 patients were not regarded as having tongue atrophy on clinical neurological examinations. Therefore, the evaluation of midsagittal MRIs is clinically useful. PMID- 1628457 TI - [A case of myasthenia gravis complicated by cyclic thrombocytopenia]. AB - A 47-year-old woman with myasthenia gravis for last 11 years was admitted because of relapsed muscle weakness, hypermenorrhea and thrombocytopenia. Physical and neurological examinations revealed diplopia, proximal muscle weakness and purpuras on the left arm and bilateral legs. Repeated hematological examinations revealed cyclic fluctuation of platelet counts which spontaneously changed from the nadir levels of 12-27 x 10(3)/microliters to the peak levels of 150-400 x 10(3)/microliters. The platelet count reached a nadir at the onset of menstruation. Platelet-associated IgG (PAIgG) was within normal level when platelet count was at an increasing phase. Survival time of autologous platelets was normal when platelet count was at an increasing phase. Megakaryocytes in the bone marrow were apparently normal at the nadir phase. The patient's serum obtained at the nadir of platelet count significantly suppressed megakaryocyte colony forming unit (Meg-CFU) formation in comparison with that after the stabilization of platelet count, suggesting that this cyclic thrombocytopenia was secondary to cyclic hypoproduction of megakaryocytes caused by a suppressive factor. On the other hand muscle weakness showed no cyclic fluctuation. Administration of 60 mg/day prednisolone stabilized the platelet count at about 280 x 10(3)/microliters, abolished hypermenorrhea and gradually improved muscle weakness. These findings suggested autoimmune mechanism in the production of a Meg-CFU-suppressive factor might be involved in the pathogenesis of thrombocytopenia. PMID- 1628458 TI - [HTLV-I associated myelopathy with bilateral abductor vocal cord paralysis--case report]. AB - We have reported a 50-year-old woman with HTLV-I associated myelopathy (HAM) who had bilateral abductor vocal cord paralysis. The symptoms and signs were slowly progressive spastic paraplegia, dysuria, inspiratory stridor, and snoring during sleep. She had no hoarseness. Titers of anti-HTLV-I antibody were elevated in both the serum and cerebrospinal fluid. FEV1.0% on the spirogram was reduced to 66%. The fiberscopic examination demonstrated the abductor limitation of the vocal cords during the inspiratory phase. During induced sleep after the intravenous administration of thiopental sodium, this abductor paralysis was worsened, producing a high pitched inspiratory stridor. The adduction was not disturbed at all. Needle electromyogram of the posterior crico-arytenoid muscle which is a sole abductor muscle revealed the high amplitude up to approximately 1.0 mV (normal less than 0.8 mV) with poor interference pattern, indicating neurogenic changes. After 2 months course of prednisolone (60 mg/alternative day), FEV1.0% was recovered to be 92% with the improvement of the gait disturbance, which suggests the abductor vocal cord paralysis is related to HAM. The abductor vocal cord paralysis in HAM would require a careful follow-up observation to protect the respiratory failure in the advanced stage. PMID- 1628459 TI - [A case of benign intracranial hypertension with bilateral reversible thalamic lesions on magnetic resonance imaging]. AB - A 10-year-old girl had complained of headache, vomiting and blurred vision for one month before admission to our hospital. Her neurological findings were normal, except that the examination of the fundi revealed papilledema. The cerebrospinal fluid pressure was elevated to 220 mmH2O. The brain MRI showed bilateral and approximately symmetrical hyperintense areas located in the thalamus. These disappeared on the repeated MRI, and her symptoms regressed spontaneously within a month. Her illness was diagnosed as benign intracranial hypertension because of the favorable clinical course. These reversible thalamic lesions might be due to circulatory insufficiency associated with intracranial hypertension. PMID- 1628460 TI - [A case of optic neuritis associated with anticardiolipin antibodies]. AB - We reported a case of optic neuritis with the persistence of severe visual loss and central scotoma in a 26-year-old woman who was proven to have biologic false positive test for syphilis, and the elevated serum titres of IgG and IgM anticardiolipin antibodies. C.S.F. findings showed the absence of oligoclonal bands and the presence of IgM anticardiolipin antibody. She was treated twice at intervals of two weeks with methylprednisolone 1000 mg intravenously daily for three days (pulse therapy), and was started on oral prednisolone 60 mg daily which tapered gradually. After the second treatment of the pulse therapy, her visual acuity was improved remarkably and the titre of anticardiolipin antibodies became normal. Her clinical course seemed to be different from that of the optic neuritis of multiple sclerosis, in which many of patients recover near normal visual acuity after a first attack. We suggested that antiphospholipid antibodies might play a role in the etiology of her optic neuritis. PMID- 1628461 TI - [Intramuscular degeneration process in Duchenne muscular dystrophy--investigation by longitudinal MR imaging of the skeletal muscles]. AB - Intramuscular degeneration process of Duchenne dystrophy skeletal muscles was investigated by longitudinal skeletal muscle imaging with high-field-strength NMR CT of 1.5 Tesla. Thigh muscles in 10 cases ranging in age from 4 to 19 years were examined by T1-weighed longitudinal images (TR = 215-505 ms, TE = 19-20 ms). Following results were obtained: (1) Skeletal muscle degeneration was depicted as high signal intensity area reflecting its high fat contents. (2) These high signal intensity areas had a longitudinally streaky appearance in parallel direction with myofibers. (3) These findings were more prominent toward myotendon junction than muscle bellies. (4) Skeletal muscle degeneration progressed rapidly between 7 to 10 years of age, and reached a plateau after that. PMID- 1628462 TI - [DNA diagnosis of X-linked recessive bulbospinal muscular atrophy by androgen receptor gene mutations]. AB - X-linked recessive bulbospinal muscular atrophy (BSMA) is an adult-onset form of motor neuron disease, of which androgen receptor (AR) gene mutations with increased size of a polymorphic tandem CAG repeat in the coding region was found by Fischbeck et al (1991). We investigated this AR gene abnormality by polymerase chain reaction (PCR) in 16 unrelated Japanese BSMA pedigrees, including 21 patients, 11 male siblings without any neurological signs and 9 female siblings. PCR products for AR-CAG repeat obtained from 21 affected individuals were enlarged in fragment size (about 100 bp longer than normal control size), whereas those from clinically unaffected brothers of the patients and their offsprings were all normal in size. Moreover, PCR products from 8 obligate heterozygous females (carriers) consisted of two different fragments with enlarged and normal size. Our results confirmed the findings reported by Fischbeck et al, and indicated that the detection of this AR gene mutations with increased size of a polymorphic tandem CAG repeat is beneficial for pre-onset diagnosis or carrier detection of this disease. PMID- 1628463 TI - Postcircumcision urinary tract infection. AB - The possible association of urinary tract infection (UTI) with ritual circumcision on the eighth day of life was studied by analyzing the epidemiology of urinary tract infections during the first year of life in 169 children with UTI (56 males and 113 females) born in Israel from 1979 to 1984. Forty-eight percent of the episodes of UTI occurring in males appeared during the 12 days following circumcision, and the increased incidence during that period was highly significant. The median age of the males at the time of the UTI was 16 days, compared with seven months in females. Ritual Jewish circumcision as practiced in Israel may be a predisposing factor for UTI during the 12-day period following that procedure. PMID- 1628464 TI - The death of a child with diabetes from neglect. A case study. AB - This case report of a child with insulin-dependent diabetes mellitus (IDDM) describes a naturally occurring ABABCA design. The A condition represents poor diabetes management provided in the home setting, and the B and C conditions represent improved diabetes management in residential treatment (condition B) or foster care (condition C). The A condition was consistently associated with episodes of diabetic ketoacidosis, high glycosylated hemoglobin percentage, and school failure. In contrast, the B/C conditions were consistently associated with improved health status and school performance. On two occasions, the child was returned to condition A by the state's protective service agency (HRS) in direct conflict with the recommendations of the child's psychological and medical treatment staff. During her last condition A placement, the youngster died. Chronically ill children who are neglected may not receive the protection they need because of lack of awareness about the psychosomatic aspects of their problem. PMID- 1628465 TI - A treatment program for adolescents with phenylketonuria. AB - A treatment program for adolescents with phenylketonuria (PKU), incorporating education, goal-setting, self-monitoring, contracts, and rewards, was evaluated by measuring knowledge of PKU, blood phenylalanine concentrations, and health locus of control (LOC) before and after participation in the program. Of the 16 subjects, seven subjects successfully completed the program by achieving behavioral goals. These subjects increased their knowledge of PKU and decreased their blood phenylalanine concentrations, but the nine nonsuccessful subjects did not. There was no significant change in LOC scores for either group. There was a significant relationship between baseline blood phenylalanine levels and success with the program. Therefore, this pilot study demonstrates that adolescents who have already achieved some measure of metabolic control can be expected to be most successful with this program and realize the greatest benefits from it in the form of increased knowledge of PKU and even better metabolic control. PMID- 1628466 TI - Growth and academic achievement in inner-city kindergarten children. The relationship of height, weight, cognitive ability, and neurodevelopmental level. AB - Measures of height, weight, nonverbal cognitive ability (Ravens progressive matrix), visual-motor-perceptual ability (Beery-Buktenica test of Visual Motor Integration [VMI]), the imitation-of-gestures technique, and academic achievement (Stanford Early Achievement) were obtained for a sample of 82 children from a poor inner-city community. In contrast to prior reports from the United States and about other developed countries, anthropometric measures were related both to academic achievement and to these measures of neurodevelopment. They were not consistently related to measures of nonverbal cognitive ability. Regression analyses revealed that general cognitive ability contributed more variance (39%) to predictions of achievement than all other variables, including weight for age (13%) and VMI (6%). Children with reduced somatic growth were likely to do poorly in school, but the data do not show that undernutrition causes learning failure. Rather, they suggest that environmental problems affecting the development of thought processes and nutrient intake precede both growth and learning failure. PMID- 1628467 TI - Fiberoptic vs conventional home phototherapy for neonatal hyperbilirubinemia. AB - Two methods of administering home phototherapy were compared. Twenty-two infants received home phototherapy with a fiberoptic cummerbund, and 26 infants received home phototherapy with a conventional four-bul "bililight." The two treatment modalities proved equally effective in lowering bilirubin levels. The duration of treatment was a mean of 3.09 days in the fiberoptic group and 2.77 days in the bililight group, and the daily decline in bilirubin levels was a mean of 1.84 mg/dL/day in the fiberoptic group and 2.18 mg/dL/day in the bililight group. Differences were not statistically significant (Student's t-test, two-tailed). Upon completion of therapy, mothers responded to 15 statements intended to measure attitudes and perceptions regarding home phototherapy. In four of the 15 statements there was a statistically significant preference for fiberoptic therapy, as measured with the chi-square statistic (p less than .05), while in the remaining statements there were no preferences expressed toward either treatment modality. Fiberoptic home phototherapy appears to be as effective as home phototherapy administered with conventional bililights and may be better accepted by parents. PMID- 1628468 TI - A new light on jaundice. A pilot study. PMID- 1628469 TI - Babies who don't cry. PMID- 1628470 TI - Lead ingestion in a pattern of repetitive injury. PMID- 1628471 TI - Unique congenital features in tuberous sclerosis. PMID- 1628472 TI - Perinatal loss. A critique of current hospital practices. AB - Dramatic improvements in the hospital management of perinatal loss have taken place in the past 20 years. However, there has been no critical examination of current approaches. Four possible hazards of current hospital practice are described: 1) Institutionalization of bereavement: Instead of offering parents an empathic awareness of the unique dimensions of their perinatal loss, caregivers often interact according to detailed behavioral protocols. 2) Idealization of contact with the dead baby: This approach may equate actual physical contact with the dead child with the more complicated and variable process of mourning. 3) Homogenization of grief: Counselors tend to denigrate different grief responses by focusing on a preconceived grief reaction. Thus, they may mistakenly label many such reactions pathologic if they deviate from the rigidly prescribed "norm." 4) Lecturing the bereaved: Telling parents the "right" thing to do may deprive them of a crucial aspect of the process that empowers parents after they experience the helplessness associated with perinatal loss--that of making their own decisions. These problems are illustrated by a clinical vignette, and alternative approaches are explored. PMID- 1628473 TI - Sexual abuse allegations in child custody cases: the role of the pediatrician. PMID- 1628474 TI - Acute acalculous cholecystitis complicating Mycoplasma pneumoniae infection. PMID- 1628475 TI - Case of primary erythromelalgia in a child. PMID- 1628476 TI - Enteroviral meningitis following Haemophilus influenzae type b meningitis. PMID- 1628477 TI - Temporary blindness due to sodium nitroprusside overdosage in a postoperative patient: an unusual adverse effect. PMID- 1628478 TI - Chronic fatigue syndrome. AB - Chronic Fatigue Syndrome appears to represent a spectrum of disorders in which a variety of pathophysiological mechanisms may operate. While the initiating event in the majority of patients is a pyrexial illness, possibly due to enterovirus infection, evidence of persisting infection or inflammatory changes in muscle and/or brain remain unconvincing. CFS patients display a definite reduced aerobic work capacity compared to normal control subjects, but this may reflect a state of deconditioning resulting from prolonged physical inactivity. They also have an altered perception of their level of exertion and premorbid fitness. The characteristic fluctuation in symptoms, with periods of relapses and partial remissions, may indicate that some central disorder of sensory perception is operational. It may be that a primary sleep disorder results in a reduced sensory threshold for afferent stimuli from muscle. This could well account for many of the subjective symptoms which patients experience. Much more research is clearly necessary if we are to achieve a better understanding of this distressing and at present enigmatic disorder. PMID- 1628479 TI - The role of electrodiagnostic studies in the diagnosis and management of polymyositis. AB - Polymyositis is an inflammatory muscle disease preferentially affecting proximal muscles. Diagnosis is suggested by an EMG study showing abnormal spontaneous activity in proximal muscles and the presence of myopathic motor unit changes. Alternative diagnoses are eliminated by nerve conduction and neuromuscular junction studies and the EMG. Diagnosis is confirmed by muscle biopsy. Treatment requires aggressive and long term immunosuppressive therapy. Expectations for improvement in strength are good, but complete remission or cure less predictable. Polymyositis may be associated with other systemic disorders such as collagen vascular diseases and cancer, and an appropriate evaluation should include these associations. PMID- 1628480 TI - Retinoids: uses and abuses. AB - There is no doubt that modern retinoids are a two-edged sword. While they appear to normalize many abnormal biologic processes, i.e. modulate cellular differentiation and cellular proliferation, at the same time they can severely "abnormalize" other processes, i.e. embryonic organogenesis. Pharmaceutical ingenuity in separating their toxicity from their efficacy will determine their ultimate value to the therapist. PMID- 1628481 TI - Priorities and diagnostic studies in the management of the injured patient. AB - The traumatized patient is best served by an orderly and sequential resuscitation and evaluation. Primary priorities include the establishment of a secure airway, adequate ventilation and hemodynamic status. These considerations should be followed by a brief history, systemic physical examination and radiographic studies. Studies utilized in blunt trauma include diagnostic peritoneal lavage and computed tomography. Nuclear magnetic resonance and ultrasound may prove useful in the future. In penetrating trauma, traversing missiles mandate surgical exploration. Stab wounds may be managed by several alternative methods. Emergency thoracotomy has a limited role in the blunt trauma patient but may be life saving in those suffering penetrating trauma. PMID- 1628482 TI - Current therapies using monoclonal antibodies: I. Organ transplantation, bacterial sepsis, bone marrow transplantation. PMID- 1628483 TI - Current therapies using monoclonal antibodies: II. Malignant disease. PMID- 1628484 TI - The basics of genetic disease. AB - Molecular genetics has opened new avenues for medical diagnosis, treatment and prevention of genetic diseases. Major ethical and legal issues regarding applications of this new technology have surfaced and are being discussed at a variety of levels. Policies for use of the new technology have been established, and the first use of gene replacement therapy is anticipated in the near future. PMID- 1628485 TI - Glycation alters collagen fibril organization. AB - Incubation of rat tail tendon in 0.2M ribose results in accelerated non-enzymatic glycosylation of collagen, with the formation of fluorescent cross-links between molecules and decreased solubility. Electron micrographs of tendon cross-sections show an increased fibril packing density with increasing degrees of glycation. After a one-week incubation in ribose, every fibril appears in close contact with all of its neighbors, and the packing density has increased to 76%, from a value of 62% in controls. Irregular diameters and fusion of fibrils also are seen. All of the fibrils in a bundle appear to become cross-linked together, creating a larger stress bearing unit. This model is consistent with stress-strain curves showing a large increase in tensile stress and stiffness after a one-week incubation period in ribose. The diameters of the collagen fibrils increase in size in glycated tendon. We hypothesize larger diameters result from an increased resistance to shrinkage during the specimen preparation process, as a result of the rigid sugar derived cross-links. Closer fibril packing, increased fibril diameters, and irregular diameters have been reported in diabetic tissues, and may result from decades of glycation induced cross-link accumulation. PMID- 1628486 TI - Effect of hyaluronate on physicochemical and biological properties of collagen solution which could be used as collagen filler. AB - The effect of hyaluronate (HA) on the physiochemical and biological properties of collagen solution was examined for two preparations of collagen with different rates of fibril formation. The addition of HA to the collagen preparation with the slower rate of fibril formation caused a prominent acceleration of fibril formation. A differential scanning calorimetric measurement of the collagen preparation demonstrated a stabilizing effect of HA on collagen solution after incubation at 37 degrees C. Histochemical examination of rat dermis after injection of the collagen solution into the tissue revealed the migration of fibroblast-like cells into the region occupied by the injected collagen. The addition of HA to collagen preparation S (slower rate of fibril formation) shortened the time-to-appearance of fibroblast-like cells to a similar value to that observed when collagen preparation F (faster rate of fibril formation) was used. The timing of cell appearance was in accord with the rate of fibril formation in vitro. Fibrils newly formed by injected collagen might provide sites for cell attachment, migration and proliferation. PMID- 1628487 TI - Effects of ascorbate-deficiency on collagen secretion and resorption in cultured mouse incisor germs. AB - The effects of ascorbic acid deficiency on mouse incisors, grown in vitro, has been investigated at the histological and cytological levels. In this model, continuously growing mouse incisors are characterized by the existence of different type of predentin-dentin matrix on its lingual (root-analogue) and labial (crown-analogue) surface and the absence of enamel on the lingual surface. Our observations indicated that ascorbate-deficiency affected the behavior of mouse tooth germs in vitro: odontoblast differentiation was disturbed and morphological evidence for odontoblast-mediated collagen resorption were observed. An abnormal amorphous predentin-dentin matrix existed and the basement membrane was prematurely disrupted. The dentin mineralization, as well as functional differentiation of ameloblasts were strongly hampered. Chronic deficiency led to disorganization of the dental tissues. PMID- 1628488 TI - Influence of interleukin-1 on the morphology and proteoglycan metabolism of cultured bovine articular chondrocytes. AB - Bovine articular chondrocytes cultured in agarose gel in the presence of serum elaborated a highly organized extracellular matrix rich in proteoglycans and collagens. The cultures were evaluated quantitatively by radiosulfate labeling of proteoglycans, and by densitometry following staining with alcian blue. In addition, immunohistochemical methods were used to demonstrate the presence of several components of cartilage proteoglycan molecules. Treatment with Interleukin-1 (Il-1) or retinol resulted in diminished synthesis and enhanced catabolism of matrix proteoglycans, but the chondrocytes were more sensitive to human recombinant Il-1 alpha than to Il-1 beta. Treatment with Il-1 alpha or retinol resulted in a profound disorganization of the residual matrix around the majority of the chondrocytes, while Il-1 beta caused much less severe changes. Some variation in cellular response to Il-1 alpha may result from the heterogeneity previously reported among articular chondrocytes. PMID- 1628489 TI - Hyaluronan can be non-enzymatically linked to protein through an alkali sensitive bond. AB - To test for the presence of hyaluronan to protein linkages, both purified and unpurified preparations of hyaluronan were blotted onto nitrocellulose, and the adsorbed hyaluronan was detected using a biotinylated probe derived from cartilage. While purified hyaluronan did not adsorb to nitrocellulose, the unpurified hyaluronan from rat fibrosarcoma (RFS) cells and chick embryos did. This adsorption appeared to require the presence of protein, since it was inhibited by treatment with proteases. Furthermore, when hyaluronan from RFS cells was subjected to conditions which break most non-covalent bonds, it retained its ability to adsorb to nitrocellulose, suggesting that this hyaluronan was covalently bound to protein which mediated its adsorption to nitrocellulose. While this bond was resistant to acidic buffers, it was readily broken by alkaline buffers. Additional experiments demonstrated that when either purified [3H] hyaluronan or oligosaccharide fragments of hyaluronan were incubated with a variety of proteins, they slowly gained the ability to adsorb to nitrocellulose. However, this process could be blocked by the addition of low molecular weight amines or by reducing the [3H] hyaluronan with NaBH4. These results are consistent with the possibility that the reducing terminal of the hyaluronan reacts with amine groups of protein to form a Schiff base which then rearranges to a stable bond. Such a bond could account for the association of hyaluronan with the surfaces of RFS cells. PMID- 1628490 TI - Response of plasma membrane to applied hydrostatic pressure in chondrocytes and fibroblasts. AB - Effects of applied hydrostatic pressure on transmembrane potentials were investigated in sheep articular chondrocytes and human skin fibroblasts in non confluent monolayer cultures. Resting potentials in chondrocytes (about -12 mv) and in fibroblasts (about -15 mV) were increased and decreased respectively by over 40% after pressure was applied cyclically (0.33 Hz, 120 mm Hg, 20 minutes). Continuous pressure (120 mm Hg, 20 minutes) caused deplorization in both cell types. Low frequency pressure application (less than 0.08 Hz) caused depolarization in chondrocytes and hyperpolarization in fibroblasts. Quinidine (2 x 10(-5) M) blocked and verapamil (10(-5) M) reduced hyperpolarization responses, suggesting involvement of Ca(2+)-dependent K+ channels. A23187 (1.9 x 10(-6) M) caused hyperpolarization in chondrocytes, augmented further by subsequent pressure application (0.33 Hz). Tetrodotoxin (10(-6) M) blocked depolarization responses indicating that these were due to Na+ influx. Blockade of histamine H1 receptors by chlorpheniramine maleate (5.1 x 10(-6) M), H2 receptors by cimetidine (7.9 x 10(-6) M) and beta-adrenoreceptors by sotolol (1.3 x 10(-4) M) had no effect on hydrostatic pressure-induced hyperpolarization in chondrocytes. Cytochalasin B (2 x 10(-5) M and at 4 x 10(-6) M) abolished pressure-induced hyperpolarization in chondrocytes; in contrast, applied cyclical hydrostatic pressure to cytochalasin-treated fibroblasts caused hyper-polarization, suggesting that cytoskeletal changes were involved. PMID- 1628491 TI - Characterization of a bovine synovial fluid lubricating factor. I. Chemical, surface activity and lubricating properties. AB - A lubricating glycoprotein (PSLF) with an apparent molecular weight of 280 kDa was purified from bovine synovial fluid by anion exchange, molecular sieve chromatography, and density gradient centrifugation. Lubrication was measured under boundary conditions as lowering of the coefficient of friction (mu) between oscillating natural latex and polished glass. Lubricating ability was first observed at a concentration of 200 micrograms/ml and became maximal at 260 micrograms/ml. Hydrophobic interfacial tension measurements indicated that at the former concentration, monolayers of PSLF formed. Sugar digestions showed that lubricating ability depends upon the terminal galactose of the molecule. PSLF is similar if not identical to lubricin. It is proposed that a repulsive hydration force is the molecular mechanism for lubricating activity. PMID- 1628492 TI - Characterization of a bovine synovial fluid lubricating factor. II. Comparison with purified ocular and salivary mucin. AB - Boundary lubricating activity and biochemical characteristics of purified lubricating factor from bovine synovial fluid (PSLF) were compared to those of mucinous glycoprotein from human submandibular saliva and stimulated tears. Mammalian synovial fluid and saliva contain mucinous glycoproteins which reduce the coefficient of friction (mu) in a bearing of latex:glass which isolates boundary lubrication. In contrast, mucin secreted by the lacrimal gland did not lubricate. Cleveland plotting showed that these species are not identical. PMID- 1628493 TI - Growth of mineral crystals in turkey tendon collagen fibers. AB - Bone and several other vertebrate mineralized tissues are formed by the organized growth of crystals of carbonated apatite within a matrix of type 1 collagen fibers. The development of this process in isolated fibrils of young turkey leg tendons has been studied by transmission electron microscopy. Collagen banding, presumably due to ion concentration, precedes the appearance of any crystals. The smallest crystals observed are short needles in bands near the surface of the fibrils. Longer needles, up to the length of the collagen gap regions, were also seen, and, evidently at a later stage, single crystal belts extending partly or wholly through the fibrils. Finally, in mature tendon crystal platelets, seemingly derived from the cracking of belts, extend partly into the collagen overlap zone. In the least mineralized tendon, extrafibrillar mineral-containing vesicles have occasionally been observed adjacent to regions of radiating needle crystal growth in the fibrils, and, more commonly, smaller particles adjacent to bands of very small needles. PMID- 1628494 TI - New developments in adolescent health care. PMID- 1628495 TI - Preventive cardiology for the pediatrician. PMID- 1628496 TI - Portal vein thrombosis: imaging features and associated etiologies. AB - Thrombosis of the portal vein and its splanchnic tributaries is often unsuspected clinically and may be recognized only after imaging studies of the abdomen are performed for other reasons. Radiologists should be aware of the clinical situations that predispose a patient to portal or mesenteric vein thrombosis and should also be able to recognize the sequelae of chronic thrombosis. Different modalities can be used to image the patient with portal vein thrombosis; each has its strengths and drawbacks. This paper discusses the conditions that predispose to portal and mesenteric vein thrombosis, differentiating intrahepatic portal vein occlusion secondary to liver disease from extrahepatic portal vein occlusion associated with a normal liver. The imaging features of portal vein thrombosis, its associated causes and sequelae will be reviewed as demonstrated on computed tomography (CT), ultrasound, magnetic resonance imaging (MRI), angiography, and plain film. PMID- 1628497 TI - Clostridium botulinum C3 ADP-ribosyltransferase. AB - C3 and C3-like ADP-ribosyltransferases modify the low-molecular-mass GTP-binding proteins Rho and Rac. ADP-ribosylation occurs in asparagine-41, which is located in the putative effector region of these highly conserved regulatory proteins. First studies indicate that the Rho proteins are somehow involved in the regulation of cytoskeletal proteins, e.g., microfilament proteins. Although the precise mechanism of the interaction of the C3 substrate with cytoskeletal elements is unclear, it appears that the ADP-ribosylation by C3 renders the GTP binding protein biologically inactive. Thus C3 and/or C3-like ADP ribosyltransferases may be useful instruments with which to study the physiological functions of its eukaryotic substrates. Moreover, those studies may help to elucidate whether these exoenzymes are of pathophysiological and pathogenetic relevance in diseases caused by clostridia producing these agents. PMID- 1628499 TI - ADP-ribosylation of signal-transducing guanine nucleotide-binding proteins by pertussis toxin. PMID- 1628498 TI - Diphtheria toxin and Pseudomonas aeruginosa exotoxin A: active-site structure and enzymic mechanism. PMID- 1628502 TI - A dermatologic diary. Portrait of a practice. PMID- 1628501 TI - 18th World Congress of Dermatology. PMID- 1628500 TI - Clostridial actin-ADP-ribosylating toxins. PMID- 1628503 TI - Suction purpura: Part I. "Sucker daddy" or "cyclops" purpura. PMID- 1628504 TI - Natural history and treatment of scalp psoriasis. AB - The scalp is a common site of involvement at onset and throughout the course of psoriasis. Worldwide census studies report that approximately half of the psoriasis population are afflicted with psoriasis of the scalp. We describe the frequency, clinical aspects, and treatment of scalp psoriasis in childhood, adulthood, and in the geriatric age groups. Measures of prevention and control are reviewed. PMID- 1628505 TI - Solar exposure in children. PMID- 1628506 TI - Isolated cases of palmoplantar keratoderma, Unna-Thost type. AB - A study on the prevalence of hereditary palmoplantar keratoderma, Unna-Thost type, was carried out in Croatia. Altogether 205 cases were verified, and of these forty-eight were chosen for further studies. Six isolated cases of hereditary palmoplantar keratoderma, Unna-Thost type, were found. The following theories were considered to explain such a phenomenon: spontaneous mutation, reduced gene expression, incomplete penetration of the gene, late onset of the disease, unknown biological father of the proband, and involvement of genes in addition to the autosomal dominant one. PMID- 1628507 TI - Contributions to the treatment of dermatologic manifestations of Lyme borreliosis. AB - Lyme borreliosis was identified in Czechoslovakia for the first time in 1985. Since then, more cases have gradually been identified. Since 1989, about 1,500 patients per ten million inhabitants have been reported every year. Having summarized the results of the therapy of 371 patients with dermatologic manifestations of lyme borreliosis (erythema migrans in 315, borrelial lymphocytoma in fifteen, and acrodermatitis chronica atrophicans in forty-one) we present the antibiotic regimens used by Czechoslovak dermatologists in clinical practice. PMID- 1628508 TI - Acanthoma supratrochantericum. AB - We report the cases of five patients with lesions of benign reactive hyperplasia of the skin in the hip joint region. In view of the distinct clinical features, and in analogy with previously reported cases of acanthoma fissuratum, we termed this condition acanthoma supratrochantericum. PMID- 1628509 TI - Actinic granuloma in alcoholic liver disease. AB - Actinic granuloma is a rare condition. Its acceptance as a defined disease has been queried several times. The authors observed a classic case in a patient with alcoholic cirrhosis of the liver and diabetes. The possible role of metabolic disturbances in the pathogenesis of this syndrome is reviewed. PMID- 1628510 TI - Therapeutic options for erythroderma. AB - In this work we will discuss some of the dilemmas and therapeutic options in the treatment of patients with erythroderma. We will mention treatment modalities for psoriatic erythroderma and review briefly one illustrative case in which a new experimental approach was utilized. PMID- 1628511 TI - Multiple carcinoma in patients with psoriasis caused by psoralen-ultraviolet A therapy, natural killer cell insufficiency, or intensified sun exposure? AB - A case is presented of a patient with psoriasis in whom squamous cell carcinoma most likely occurred due to the interaction of various factors (psoralen ultraviolet A therapy, sun exposure, and suppression of natural killer cell function). Therapy consisted of 1 mg/kg/daily of etretinate (Tegison), which resulted in clearing of psoriatic lesions in one month's time. New carcinomas did not develop and natural killer function improved. PMID- 1628512 TI - Autosomal recessive ectodermal dysplasia. AB - Seven cases of a peculiar autosomal recessive ectodermal dysplasia as a distinct nosologic entity are presented. The main symptoms of this rare, not fully delineated syndrome, are hypohidrosis, xeroderma, hypotrichosis, dystrophy of the teeth, benign acanthosis nigricans, and furrowed tongue. Other symptoms can include mental retardation, nail dystrophy, disturbances of skin pigmentation (perioral and periorbital hyperpigmentation, vitiligo, and perinevic leukoderma), and palmoplantar keratosis. PMID- 1628513 TI - Subcutaneous symmetrical morphea with unusual onset as nodular vasculitis. AB - We present a case of widespread subcutaneous symmetrical morphea that started as nodular vasculitis. The characteristics histologic features were abundant inflammatory infiltrates in the subcutis, fascia, and muscle, with numerous macrophages and extensive vascular changes. PMID- 1628514 TI - Two cases of unilateral verrucous nevus. AB - We report two patients with epidermal nevus: one with linear verrucous nevus and one with inflammatory linear verrucous epidermal nevus. The patients first showed manifestations of nevus at different ages (soon after birth and at the age of seven), and the findings progressed differently. In both cases, warty plaques were located unilaterally, strictly following Blaschko's lines. PMID- 1628516 TI - Gynecological tumors. Recent progress in diagnostic pathology. PMID- 1628515 TI - Sweet's syndrome in patients with kidney and liver disorders. AB - Two patients with Sweet's syndrome are described. In the first patient the disorder was associated with urinary stone disease and in the second with chronic hepatitis. We compared skin lesions in patients with kidney and liver diseases with those in Sweet's syndrome. In both patients all skin manifestations disappeared when the underlying disorders were treated. No corticosteroids were used. PMID- 1628517 TI - Flow cytometry of ovarian neoplasms. PMID- 1628518 TI - Oncogenes in gynecological tumors. AB - Evidence is increasing that proto-oncogenes and cancer suppressor genes are involved in the development and/or progression of gynecological malignancies. While histopathologic examination remains an indispensable tool of the surgical pathologist in the diagnosis and evaluation of patients with gynecological malignancies, the advancement to technology and the development of new knowledge regarding neoplastic transformation are providing a basis for new opportunities to improve patients care. These new opportunities will depend on the use of the skills and reagents developed in the basic medical science laboratories. Thus, it is important for those in the field of diagnostic pathology to begin to acquire a knowledge of proto-oncogenes and cancer suppressor genes as well as a basic understanding of the techniques used to detect and evaluate them. PMID- 1628519 TI - Cervical intraepithelial neoplasia and microinvasive carcinoma of the cervix. PMID- 1628520 TI - Circannual prolactin rhythm in intact dogs housed outdoors. AB - Prolactin (PRL) and progesterone (P4) values were collected from eight intact (4 female, 4 male) mixed-breed dogs housed outdoors for a two-year span. A circannual component was significant for PRL for each dog (P less than 0.01) and the rhythm was validated for the population (P less than 0.004). Females had two estrus periods a year demonstrated by a P4 frequency of 23.5 +/- 0.47 wk. A 6 month component was statistically significant for P4 for three dogs and of borderline statistical significance for the fourth dog. Circannual acrophases yielded a statistically significant population rhythm (P = 0.012), whereas the 6 month component was of borderline statistical significance (P = 0.056). No time macroscopic relationship between PRL cycles and P4 cycles was seen. These findings are consistent with similar PRL rhythms in non-domestic canids and emphasize the importance of considering seasonal effects when interpreting PRL data. PMID- 1628521 TI - Usefulness of circadian amplitude of blood pressure in predicting hypertensive cardiac involvement. AB - Twenty-four-hour blood pressure (BP) profiles of 56 patients diagnosed as 'hypertensive' by WHO criteria were analyzed by the fit of a 24-hour cosine curve according to the single cosinor method. A left ventricular mass index (LVMI) was also assessed by two-dimensional echocardiography on each patient as a gauge of target organ involvement. LVMI and the BP MESOR correlates positively for systolic, S (r = 0.324), mean arterial, MA (r = 0.334) and diastolic, D (r = 0.267) BP (P less than 0.05), yet no statistically significant linear correlation between LVMI and the circadian BP amplitude (one-half of predictable change) was found. When a second-degree polynomial regression was fitted to the circadian BP amplitudes, an association was found (SBP: R2 = 0.138, P = 0.02; MAP: R2 = 0.167, P = 0.01; DBP: R2 = 0.128, P less than 0.01). The corresponding curves were characterized by peaks in the circadian amplitudes of SBP, MAP and DBP around a value of LVMI between 110 and 120 g/m2. For further scrutiny, three subgroups had been formed on the basis of literature, a priori with respect to the LVMI (group 1: LVMI less than 100); group 2: 100 less than LVMI less than 130; group 3: 130 less than LVMI). For MESORs, there was no difference between groups 1 and 2, whereas the MESOR of group 3 were larger than the other two groups. The circadian BP amplitudes of group 2 were larger than those of the other two groups for SBP, MAP and DBP. An increasing LVMI precedes a definitive increase of BP MESOR and coincides with an increase in the circadian BP amplitude; thus an increase in extent of circadian changes can alert the self-monitoring population of a target organ involvement. PMID- 1628522 TI - Circannual changes in ventricular function assessed by echocardiography. AB - Cardiac function may vary predictably along the 1-year scale. A circannual rhythm, more or less in phase is documented for 5 echocardiographic variables in clinically healthy Japanese adults. PMID- 1628523 TI - Gradual adjustment of circaseptan-circadian blood pressure and heart rate rhythms after a trans-9-meridian flight. AB - Circadian and circaseptan adjustment of blood pressure and heart rate after a transmeridian flight by a family of four was relatively fast, but it was not abrupt; it was not completed during the first week in the new setting. Gradual changes continued for the ensuing three weeks. The circadian and circaseptan rhythm characteristics and their adjustment in particular differed among variables in the husband: the circadian component of heart rate adjusted more rapidly than that of blood pressure. The adjustment also differed among two members of the family. A new phenomenon, namely a difference in circadian rhythm adjustment between husband and wife, is also described herein: the wife's circadian rhythm in blood pressure advanced by 9 hours within the 4-week span of recording following a 9-hour advance in living routine (after a 9-zone transmeridian flight); since both schedule and rhythm moved in the same direction (albeit not at the same rate), the behavior may be dubbed concursive. By contrast, the husband delayed to achieve the same adjustment: his behavior was anticursive. The phenomenon of a difference in direction of adjustment for different variables in the same subject has been described earlier as polarity, now qualified as intra-individual polarity, to separate it from the precedent of an intrafamilial or more broadly inter-individual polarity or partitioning, reported apparently for the first time and dubbed 'cursion'. PMID- 1628524 TI - Circannual modulation of blood pressure enhanced by paternal history of high blood pressure. PMID- 1628525 TI - Similarity of the nocturnal profile of serum melatonin at early puberty and early adulthood. AB - In the present study we determined the nocturnal profile of serum melatonin (MT) concentrations in 10 short normal children at Tanner stage I-II of pubertal development (12.5-14.9 yrs) and in 6 young adults (24-29 yrs). Blood was collected every 30 min from 00(00) to 06(00). We did not find any significant difference in the nocturnal profile of serum MT, as gauged by the comparison of MT concentrations at any time-point tested as well as of the transverse means (84.2 +/- 36.0 pg/ml [M +/- SD] in the children vs 78.7 +/- 10.8 pg/ml in the adults). Mean serum melatonin concentration was not correlated to sex hormone concentration or body surface area. Our findings do not support the view that MT concentrations fall at the beginning of pubertal development and that changes in body size may be the reason for age-dependent changes of serum MT concentrations. PMID- 1628526 TI - Dynamics of nonprotein and protein sulfhydryl compounds in rat gastric mucosa: possible implication for cytoprotection and ulcerogenesis. AB - The hypothesis that nonprotein and protein sulfhydryls in gastric mucosa may play some role in the defensive and offensive processes of gastric epithelium was tested in this study in the intact rat gastric mucosa. Both sulfhydryl compounds presented statistically significant changes during the 24-hour day. The content of nonprotein sulfhydryls was less during the dark span than during the light span, while the circadian acrophase of protein sulfhydryls occurred during dark span. These results may offer a new interpretation of the greater vulnerability to ulcerogenic agents of the gastric mucosa of rats during their usual activity span. PMID- 1628528 TI - Negotiating independent practice in diabetes education. PMID- 1628527 TI - Morningness-eveningness preference and sleep habits in Japanese office workers of different ages. AB - The Japanese version of the morningness-eveningness questionnaire and life habits inventory were administered to approximately 400 workers and the changes in morningness-eveningness scores and sleep-wake habits with aging were investigated. All subjects were divided into four age groups, i.e., 20's, 30's, 40's, and 50 + 60's. Morningness-eveningness scores significantly shifted to morningness preference with increased age. The results of sleep-wake habits showed that 1) there were no age-related changes for habitual sleep parameters (bedtime, arising time, and sleep length), but preferential bed and arising times significantly advanced with aging, 2) the variability of habitual sleep parameters were greater in the young than in the old, especially, on the weekend, and 3) the older the age groups were, the better the mood on arising. These findings suggested that the circadian phase was advanced and/or the period was shortened with increased age. PMID- 1628529 TI - Alternative staffing strategies for community hospital-based diabetes education programs. AB - A diabetes education program can be a valuable asset to any hospital. The purpose of this paper was to describe one method of implementing a diabetes education program using minimal human and financial resources. By minimizing paperwork and maximizing potential in staff members who were functioning in various roles, this program was able to provide quality diabetes education to a population in need. Once the benefits of a diabetes education program are established, a plan for expansion should be developed to assure its long-range growth and success. PMID- 1628530 TI - Parents of children with diabetes: what are they worried about? AB - Parental worries, specific to having a child with diabetes, have been associated with poor diabetes control. This study addressed three questions relating to this issue: Does parental worry affect the metabolic control of the child with IDDM? What specific aspects of diabetes are the most worrisome to parents? Do these concerns change with the child's age and disease duration? Parents of 93 children with IDDM were given a modified version of the Diabetes Quality of Life measure to evaluate diabetes-specific worries. No correlation was found between parental worry and the child's metabolic control. Parents of younger children expressed the largest amount of worry, yet the kinds of things that parents were most concerned about were the same, regardless of age or duration of the child's disease. PMID- 1628531 TI - Effects of a social support group, as an adjunct to diabetes training, on metabolic control and psychosocial outcomes. AB - The purpose of this present study was to evaluate a social support group as an adjunct to an intensive outpatient diabetes training program. Insulin-treated and non-insulin-treated patients (n = 204) were randomized into two groups: the control group received the training program only, whereas the experimental group was offered the same program plus eight support group meetings. At the 7-month follow-up, patients in both groups showed improved metabolic control, diabetes knowledge, frequency of practicing recommended diabetes management behaviors, and emotional adjustment. Although no additional improvement was seen in those outcome measures in patients who attended support group meetings, results of a subjective evaluation of the support group showed that patients experienced positive feelings in the groups that may contribute to patient health. A better understanding of the possible contribution of support groups to health is necessary before such groups are routinely recommended to patients. PMID- 1628532 TI - Implications of diabetes mellitus and periodontal disease. AB - The dental profession is acutely aware of oral health problems associated with diabetes mellitus and clinical manifestations indicative of occult forms of the disease. Periodontal disease is common in patients with diabetes, and its effective management in diabetic patients requires cooperation involving the patient, physician, diabetes educator, dentist, and other allied health care providers. While these patients categorically appear more prone to diseases affecting the supporting tissues of the teeth, preservation of functional dental integrity can be attained by effective control of contributing systemic and local factors. This paper will discuss periodontal disease, its relationship to diabetes, proposed mechanisms of interaction, and management of periodontal disease in the diabetic patient. PMID- 1628533 TI - Coping with a chronic disease. AB - Interviews were conducted with 55 experienced patients with insulin-dependent diabetes with the aim of identifying strategies for coping with diabetes. This study was based on a health-oriented approach known as Antonovsky's salutogenic model, which conceptualizes the person as being actively involved in maintaining biological, psychological, and social homeostasis. All patients had developed some strategy for maintaining biological balance. Twenty-two also had strategies for coping both psychologically and socially with the disease. The remaining 33 patients had developed either a psychological or a social strategy in addition to their biological strategies. The results indicate that it is important for the patient's well-being and self-esteem to establish all three coping strategies- biological, psychological, and social. The diabetes care team could be a valuable resource for the patient in this respect. PMID- 1628534 TI - Diabetes health beliefs, self-care behaviors, and glycemic control among older adults with non-insulin-dependent diabetes mellitus. AB - This descriptive study examined the relationships between diabetes-specific health beliefs and adherence to the diabetes regimen and glycemic control in 102 older subjects with non-insulin-dependent diabetes mellitus. Health beliefs and self-care behaviors were assessed by self-report questionnaires. Glycemic control was assessed by HbA1c values. Perceived barriers to treatment were related to adherence, while perceived severity of disease was related to glycemic control. No significant associations were found between other health belief model subscales and adherence or glycemic control. Subjects not on diabetes medication had better glycemic control than those on medication. Subjects with more recently diagnosed diabetes also had better glycemic control. Practice and research attention should include older diabetic persons' perceived barriers to performing diabetes-specific self-care behaviors and perceived severity of the disease to identify potential health beliefs that may need to be altered for improving glycemic control. PMID- 1628535 TI - Abstracts from the 19th American Association of Diabetes Educators (AADE) Annual Meeting. PMID- 1628536 TI - The role of leukocyte-generated reactive metabolites in the pathogenesis of idiosyncratic drug reactions. AB - Evidence strongly suggests that many adverse drug reactions, including idiosyncratic drug reactions, involve reactive metabolites. Furthermore, certain functional groups, which are readily oxidized to reactive metabolites, are associated with a high incidence of adverse reactions. Most drugs can probably form reactive metabolites, but a simple comparison of covalent binding in vitro is unlikely to provide an accurate indication of the relative risk of a drug causing an idiosyncratic reaction because it does not provide an indication of how efficiently the metabolite is detoxified in vivo. In addition, the incidence and nature of adverse reactions associated with a given drug is probably determined in large measure by the location of reactive metabolite formation, as well as the chemical reactivity of the reactive metabolite. Such factors will determine which macromolecules the metabolites will bind to, and it is known that covalent binding to some proteins, such as those in the leukocyte membrane, is much more likely to lead to an immune-mediated reaction or other type of toxicity. Some reactive metabolites, such as acyl glucuronides, circulate freely and could lead to adverse reactions in almost any organ; however, most reactive metabolites have a short biological half-life, and although small amounts may escape the organ where they are formed, these metabolites are unlikely to reach sufficient concentrations to cause toxicity in other organs. Many idiosyncratic drug reactions involve leukocytes, especially agranulocytosis and drug-induced lupus. We and others have demonstrated that drugs can be metabolized by activated neutrophils and monocytes to reactive metabolites. The major reaction appears to be reaction with leukocyte-generated hypochlorous acid. Hypochlorous acid is quite reactive, and therefore it is likely that many other drugs will be found that are metabolized by activated leukocytes. Some neutrophil precursors contain myeloperoxidase and the NADPH oxidase system, and it is likely that these cells can also oxidize drugs. Therefore, although there is no direct evidence, it is reasonable to speculate that reactive metabolites generated by activated leukocytes, or neutrophil precursors in the bone marrow, could be responsible for drug-induced agranulocytosis and aplastic anemia. This could involve direct toxicity or an immune-mediated reaction. These mechanisms are not mutually exclusive, and it may be that both mechanisms contribute to the toxicity, even in the same patient. In the case of drug-induced lupus, a prevalent hypothesis for lupus involves modification of class II MHC antigens.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1628537 TI - Molecular aspects of paracetamol-induced hepatotoxicity and its mechanism-based prevention. PMID- 1628538 TI - Lead-induced cell proliferation and organ-specific tumorigenicity. AB - While lead acetate is a renal carcinogen in rodent studies, the mechanism by which it induces cancer has not been established. This report proposes that the enhanced susceptibility of renal tubular epithelial cells to lead-induced mitogenicity at the levels comparable to those administered in the cancer bioassay may contribute to the carcinogenic response seen in this target organ. Of relevance is that the nonresponsiveness of the liver to lead-induced carcinogenicity was associated with significantly less capacity (i.e., 675-fold) of lead to induce the mitogenic response in the rodent liver. PMID- 1628540 TI - Leishmaniasis: what is new in transmission? PMID- 1628539 TI - Choosing an oral 5-aminosalicylic acid preparation for ulcerative colitis. PMID- 1628541 TI - Evaluation of topical ketoconazole in cutaneous leishmaniasis. AB - The efficacy of topical ketoconazole in cutaneous leishmaniasis (CL) caused by L. major was assessed in an open trial. Ten patients with twenty two lesions of CL, confirmed by smear/or biopsy, were recruited into the study. Of the twenty two lesions treated, three increased in size and lesion characteristics worsened, ten showed no change but in nine there was some improvement in lesion characteristics. No lesion healed completely. No side effects were reported in nine. Topically applied ketoconazole is safe but does not significantly alter the course of CL. The differences in the results of systematically administered and topically applied ketoconazole may be due to differences in the pharmacokinetics of the drug when it is administered by different routes. PMID- 1628542 TI - The efficacy and tolerability of enalapril--hydrochlorothiazide combination as a first line therapy in black patients with mild to moderate arterial hypertension: a clinical study in Kenya. AB - The study aimed at evaluating tolerability and efficacy of the combination enalapril 20 mg with hydrochlorothiazide 12.5 mg (co-renitec) as first line therapy in black patients with mild to moderate primary hypertension. Fifty patients completed a twelve weeks of open clinical study preceded by two weeks of washout period. They were evaluated every four weeks and haematological, biochemical urine microscopy and electrocardiographic tests were undertaken before the start and after the completion of study. Pre-treatment values of mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 172.16 mm hg (+/- 20.41) and 104.38 mm hg (+/- 7.339) respectively. The usual daily dosage was one tablet which was increased to two after eight weeks in case the DBP was not normalized, i.e. less than or equal to 95 mm hg. In 44 (88%) patients, the DBP was normalised at the end of the study period; three patients (6%) were resistant to treatment and another three (6%) exhibited labile response to the treatment. Clinical tolerance was considered to be very good with only five episodes of headache, backache and anxiety, probably not related to the test drug. Biological tolerance was excellent: there was no change in the haematologic parameters; there was a decrease of 5% in mean blood urea, of 9% in the mean serum creatinine and of 4% in the mean serum uric acid and a 5% increase in plasma potassium from 3.99 to 4.28 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628543 TI - Breast cancer in Kenya: a histopathologic and epidemiologic study. AB - During 1981-1985, 417 cases of breast cancer were seen at the Department of Human Pathology, Kenyatta National Hospital, Nairobi, Kenya. During this period, 8041 cases of cancer were reported. Cancer of the breast accounted for 5% of all malignancies in Kenya and only second in number to cancer of the cervix. The incidence rate in females was 1.08 per 100,000 person-years. The incidence was low because the rural Kenyans have difficult access to the oncology facilities in Nairobi. The age specific incidence rates decreased after menopause. This is also found in other African countries but is in contrast with North America and Europe, where there is a rise after menopause. Young age of the first pregnancy, many pregnancies and a low fat content of the diet may contribute to the low incidence in post menopausal women. The distribution of the histological types was the same in Kenya with predominance of premenopausal cases and in the western world with predominance of postmenopausal cases. Invasive ductal carcinoma was the most common cancer type. Poorly differentiated tumours were common. This is probably explained by the fact that most patients seek medical help at a late state with advanced cancer. Only two cases of non-invasive intraductal carcinoma were found and in cases where lymphnodes were removed 88% had metastases. PMID- 1628544 TI - ABH secretor status in saliva of Calabar Municipality residents. AB - One hundred and seventy six healthy residents of Calabar Municipality were investigated for the presence of salivary ABH substances. Saliva and blood samples collected were analysed by haemagglutination inhibition and standard tube ABO grouping methods respectively. 86.90% and 13.10% of the subjects were ABH secretors and non-secretors respectively. A significant correlation was established between the secretor status frequency and ABO blood group phenotypes (P less than 0.001). No correlation was established with age or sex. O blood group subjects had higher titre of H-substances than A and B subjects while AB subjects had the lowest. In AB subjects, the A titre was usually higher than that of B substances. The gene frequencies for Se and se were 0.6390 and 0.3610 respectively while the phenotype prevalence rates for Se/se, Se se and se se were 40.83%, 46.15% and 13.10% respectively. It is concluded that the prevalence rate of non-secretors which has been associated with the occurrence of duodenal ulcer is low in the locality. PMID- 1628545 TI - Visceral leishmaniasis and malaria prevalence in West Pokot District, Kenya. AB - The prevalence of visceral leishmaniasis and malaria in the human population of West Pokot district of Kenya was studied in 1986. A total of 2139 people was proportionately screened for the two diseases according to four age categories (0 4, 5-14, 15-44 and greater than 45 years). Diagnostic methods included the enzyme linked immunosorbent assay (ELISA) and Leishmanin skin test for visceral leishmaniasis, and parasitological examination for malaria. The epidemiological value of the spleen rate was evaluated in relation to visceral leishmaniasis and malaria endemicity. A general decline of infection rates with altitude was observed for both diseases. Visceral leishmaniasis was less prevalent than malaria, with less than 2% active cases in any age group and had the same distribution in both sexes. Malaria infection rate was highest in the younger age groups, declining from 21.5% in the 0-4 year old age group to 5.5% in people more than 45 years old. Malaria affected significantly more males than females. The spleen rate was inappropriate for epidemiological survey of either malaria or visceral leishmaniasis due to an overlap in the distribution of the two diseases. PMID- 1628546 TI - Prevalence of juvenile periodontitis in national youth service trainees. AB - The prevalence of juvenile periodontitis was studied in a group of young adults aged 18 to 26 years from the National Youth Service. The study group consisted of a random sample of 350 trainees, 250 males and 100 females. The subjects were examined for plaque scores, gingivitis and pocket depths. Radiographs were used to show bone loss and confirm diagnosis of juvenile periodontitis. Only one subject was diagnosed as having juvenile periodontitis. This represents a prevalence of 0.28% which falls within the range of published prevalence of 0.1% to 3.4% among young adults. PMID- 1628547 TI - Prevalence and distribution of trachoma in the Luapula Valley, Zambia. AB - A cross-sectional population based study was done to provide information on the extent to which xerophthalmia and trachoma contribute to blindness in the valley population. A total of 4271 children aged under 6 years and 2503 individuals aged 6 years and more were examined. The overall prevalence of trachoma for those under 6 years of age was 17.6%, the majority of which were graded as follicular trachomatous inflammation. The trend in age specific prevalence was highly significant (x2 = 160.6, p = 0.000). Prevalence by sex was also significantly different (z = 2.0, P less than 0.05). Among those aged greater or equal to 6 years, 331 (13.2%) had trachoma. Complications of trachoma (trichiasis and opacities) were common in this age group compared to those under 6 years of age. There were no differences in prevalence by district either in children or adults. This survey provides some of the first reliable data on prevalence of trachoma in this population and that it is a significant public health problem in the valley. The magnitude of severe complications from trachoma is low in this community, this may mean that the trachoma seen is the non-blinding type. We conclude that trachoma is of public health importance in the valley but is not a major cause of blindness. PMID- 1628548 TI - Does the "Baby Cloche" heat shield keep low birth-weight infants warm? AB - To determine whether the "Baby Cloche" heat shield improves temperature control in low birth-weight infants we compared serial temperatures in 11 preterm infants nursed with or without the Cloche. Mean birth weights were 1490 and 1510 gm, mean weights at time of study 1680 and 1710 gm and mean postnatal age 20 and 27 days for study and control infants respectively. Serial measurements of rectal, abdominal skin, dorsum of the foot, Cloche wall and room temperature were recorded once or twice daily for 2 to 5 days. Mean rectal temperatures increased with increasing age from 35.3 in the first week of life to 37.0 degrees C by the third week (P less than 0.001). In infants nursed under the Cloche who were over 2 weeks of age mean rectal, abdominal and foot temperatures were 0.5, 0.6 and 1.6 degrees C higher (P less than 0.001); in younger infants there was no significant difference in any of the temperatures. Our findings suggest that the "Baby Cloche" improves temperature control in preterm infants over 1600 gm who are more than 2 weeks of age. PMID- 1628549 TI - Sheehan's syndrome in a developing country, Nigeria: a rare disease or problem of diagnosis? AB - Over a five year period, 11 cases of Sheehan's syndrome were seen in the Endocrinology Unit of a teaching hospital in Ibadan, Nigeria. The mean age at diagnosis was 35.1 years; the mean parity was four and the average interval between the obstetric injury and diagnosis was 6.9 years. Four patients were in middle socio-economic class and seven were in low socio-economic class. The most frequent presenting symptoms were failure of lactation (11 out of 11 patients) and amenorrhoea (9 out of 11 patients). Seven patients had multiple endocrine insufficiency involving essentially all pituitary cell types. Six out of 8 patients were lost to follow-up. In a review of autopsy records over a 5-year period at the same institution, out of 1,951 post-mortem examinations, no additional cases of Sheehan's were found. With an average of about two clinical cases per year, it would seem that Sheehan's syndrome is still a relatively rare entity in this part of the world in spite of the poor level of obstetric care generally available. There is a need for increased awareness about this disease on the part of practitioners in developing countries in order to establish whether this rarity is real or it is due to missed diagnosis. PMID- 1628551 TI - Coping with embedded mandibular wisdom teeth in developing countries. AB - Despite low incidence of embedded mandibular wisdom teeth (third molars) among dental patients in developing countries (less than 100/1,000), the unfavourable patients:dentist ratios, the limited resources and low levels of public awareness render them an important problem to operators in these countries. Since the effectiveness with which they are removed largely depends on the age with respect to the stage of root formation, bone resilience and relationship with adjacent anatomical structures, and the dexterity of the operator, whenever possible, early removal is recommended. To minimise occurrence of non-operative complications that are costly to manage, primary health care workers have a vital role to play in raising levels of awareness and early referral for further evaluation. In view of the risks involved in the removal of these teeth and the small number of trained oral surgeons, continuing education to the dental practitioners, could improve their efficiency in the management of this condition. PMID- 1628550 TI - Grinding machine injury of the hand: a preliminary report. AB - Case notes of 20 patients who presented with grinding machine injury to the hand from April 1984 to March 1990 were analysed for pattern of injury, method of management and outcome of treatment. Thirteen cases were seen in the last three years of this period (the SAP era) compared to seven cases in first three years of the period (the pre-SAP era). Children from low socio-economic class were the commonest victims. The right hand was commonly involved alone. Most injuries were multiple but the skin of the dorsum of the hand and ring finger were most commonly injured. Associated fractures of the metacarpals, carpals, joint dislocations in the hand and injuries to other parts of the body were uncommon. Thorough washing of the wound with soap and water, careful, limited initial debridement, elevation of the hand, antibiotics, antitetanus prophylaxis and early intensive hand physiotherapy yielded good to excellent results in seventeen patients. Eventhough the viability of the crushed skin on the dorsum of the hand may be questionable at initial presentation most of it will 'take' and we advocate that as much of this skin as is possible should be spared. PMID- 1628552 TI - Chloroquine related complete heart block with blindness: case report. AB - A 27-year old African woman with history of regular chloroquine ingestion presented with progressive deterioration of vision, easy fatiguability, dyspnoea, dizziness progressing to syncopal attacks. Ophthalmological assessment revealed features of chloroquine retinopathy, cardiac assessment revealed features of heart failure and a complete heart block with right bundle branch block pattern. The heart block was treated by pacemaker insertion and the heart failure resolved spontaneously following chloroquine discontinuation. She however remains blind. PMID- 1628553 TI - Studies on the epidemiology of leishmaniasis in Kenya: flight range of phlebotomine sandflies in Marigat, Baringo District. AB - A study on the flight range of phlebotomine sandflies using the mark-release recapture technique was undertaken in Marigat, Baringo District, Kenya, to determine the distance sandflies are able to travel and assess their importance in disease transmission. Over a period of 17 months, a total of 108,429 sandflies collected from their natural habitats were marked and released from a central point in a valley. Of these, 842 (0.8%) sandflies comprising 11 species were recaptured. Ninety-five percent of the recaptured sandflies were recovered within a radius of 50 m from the release point and 54% within a radius of 10 m. Two Sergentomyia ingrami females were recaptured at a distance of 1000 m from the release point. PMID- 1628554 TI - Quality in emergency medicine. PMID- 1628555 TI - From quality assurance to quality improvement. The Joint Commission on Accreditation of Healthcare Organizations and Emergency Care. AB - The transition from quality assurance to quality improvement is at an early stage, but it clearly has begun. The progressive anticipated changes in the tone and content of JCAHO standards will place the JCAHO in a different posture in relation to accredited hospitals. Standards are of course a set of requirements that must be met as a condition of accreditation. But the JCAHO's bottom line expectation will be a meaningful and demonstrated improvement in hospital performance. How hospitals reach this objective is their business. This shifts the onus of responsibility to where it belongs and suggests a more facilitative role for the JCAHO. Although the JCAHO is introducing standards requirements that are minimally essential to the achievement of improved performance, full-fledged adoption of CQI concepts will not be mandated. Management structures and styles in health care organizations vary considerably, and CQI is but one means to the desired end of improved performance. We believe, however, that it is the best means and that most organizations will discover this for themselves. Notwithstanding the magnitude of needed internal behavioral change, excellence in performance is what most health care organizations want for themselves and their patients. CQI offers them the opportunity to reach this lofty goal. PMID- 1628556 TI - Public policy and quality assurance. AB - The definition of quality varies widely among different key players in the American health care system. It is important for physicians and other providers to have an understanding of the public policy approach to quality assessment and assurance. Policy analysts use a number of techniques and methods in an attempt to define and balance the interests of individual patients with that of society as a whole. Benefit-cost, cost-effectiveness, and evaluation synthesis methods are used by public policy makers to arrive at rational consideration of the implications of allocation of scarce health care resources. Emergency medicine is on the forefront of many key policy decisions relative to the health care system. As the nation's health safety net, emergency medicine plays an integral and pivotal role in the definition, structure, and function of the health care system. In this regard, it is essential that emergency physicians and emergency medicine organizations play an active and formative role in the rapidly changing health care environment. Understanding conceptual approaches to the public policy approach to the health care system is an important endeavor for leadership in emergency medicine. PMID- 1628557 TI - Clinical standards. AB - The primary motivating force for standards development by emergency physicians has been the desire to establish an acceptable level of care within the specialty, followed by the growing emphasis on quality assessment and quality improvement, the measurement of which requires an existing standard of care. This article examines the process of developing clinical standards and the implication such standards will have on the practice of emergency medicine. The ACEP clinical policy for the management of chest pain is presented in depth. PMID- 1628558 TI - Industrial models of continuous quality improvement. Implications for emergency medicine. AB - CQI or TQM programs were developed from industrial models dating back to the 1930s. The original philosophic underpinnings guiding CQI included SPC, in which rigorous statistical methods were used to study industrial flow processes. As originally adopted by the Japanese, CQI is credited, to a significant degree, with the emergence of the Japanese economy as a major world leader. Nonetheless, the original CQI concepts were developed and implemented by American researchers, including Deming and Juran. The application of industrial models of quality improvement to service businesses in general and the health care industry in particular have met with substantial success in a number of different settings. Far from representing a management fad, CQI represents a solid management philosophy with a strong statistical background that stands in sharp contrast to traditional management in this country. CQI recognizes that the majority of defects result from a failure of the processes through which the product or service is generated, as opposed to the workers themselves. To a significant degree, CQI empowers service providers (through the strong commitment of top management) to participate in improving the processes through which products and services are delivered. As efforts unfold to contain health care costs and maintain quality in the face of declining resources, CQI programs are likely to be essential to success. Nonetheless, adopting CQI requires a significant commitment on the part of top management to the training and retraining of health care providers and the recognition that traditional management philosophies and techniques have largely failed to produce the quantum leaps in quality that will be required in the coming years. PMID- 1628559 TI - The cost of quality in health care. AB - The potential fiscal impact of improved quality on health care providers and organizations is substantial. In this era of dwindling health care resources, proposals that may limit cost increases while improving quality represent true win-win situations. There is a need for a substantial amount of health care research in this fertile area of quality improvement. PMID- 1628560 TI - The management of patient complaints and dissatisfaction. AB - Patient satisfaction is an integral component of the measurement of health care quality. Proper attention to patient complaints is one part of a patient satisfaction management strategy aimed at revealing and alleviating the causes of patient dissatisfaction. PMID- 1628561 TI - The quality assurance-risk management interface. AB - Involvement with both risk management and quality assurance programs has led many authors to the conclusion that the fundamental differences between these activities are, in fact, very small. "At the point of overlap, it is almost impossible to distinguish the purposes and methods of both functions from one another." "Good risk management includes real improvement in patient care through organized quality assurance activities." The interface between a proactive risk management program and a quality assurance program is dynamic and can serve the legitimate interests of both. There is little to be gained by thinking of them as separate entities and much to be gained by sharing the lessons of both. If one thinks of risk management in terms of "risk" to quality patient care, and that "assuring quality" is the most productive type of risk management, then there is no practical reason to separate one from the other. PMID- 1628562 TI - Utilization review. Emergency medicine implications. AB - The medical profession has made utilization review a priority in its efforts to limit health care expenditures. In emergency medicine this has ranged from initiatives to limit inappropriate emergency department visits to guidelines to limit emergency department testing and criteria to limit hospital admissions. The emergency department observation unit is an area in which the emergency physicians follow these practice guidelines without compromising patient care. The emergency department utilization review/quality assurance committee is a management tool by which emergency physicians monitor and implement these strategies for cost-effective patient care. PMID- 1628563 TI - Quality assurance in EMS systems. AB - QA activities in EMS systems are severely hampered unless a central agency exists to coordinate data collection, funding, and communication between agencies and field providers. EMS systems must address these issues successfully to maximize their efforts. Some regions (San Francisco, King County, Washington, Burbank, California) have developed dedicated organizations for the evaluation of prehospital care. These organizations can greatly reduce the logistic impediments to evaluating EMS care and initiating improvements. A clear goal of any QA program is improved patient care. This noble goal by itself will not move an EMS system to embrace needed changes. Other compelling reasons for organizations to support quality management activities include decreased costs resulting from improved efficiency. QA programs may improve provider morale as a result of participation in the move toward excellence, and pride in workmanship. One survey found an improved sense of teamwork after initiating these programs. Patients must receive quality emergency medical care from the moment they enter the health care system. Leadership by the medical community is crucial if this goal is to be realized. PMID- 1628564 TI - Quality assurance in the teaching hospital. AB - The approach emergency medical service (EMS) systems take to quality assurance and quality improvement is evolving rapidly. Methods of quality assurance that have been applied to the prehospital care environment are reviewed. Impediments to effective quality assurance strategies are discussed and an overview of the scope of the activities and resources necessary to perform this task is presented. The potential efficacy and limitations of quality improvement in EMS are also discussed. PMID- 1628565 TI - Computer applications in quality assurance. AB - The computer is rapidly becoming an essential tool for the physician. Proper use of computers in practice will help physicians achieve both higher levels of quality and greater consistency in patient care. Only with computers can physicians rapidly access and process all the data now needed to best address the needs of their patients. As computer use in practice becomes the standard, the inability to use these tools will be incompatible with quality care. The computer is rapidly becoming essential to modern medical management strategies that demand efficiency, accuracy, and cost effectiveness in response to patient demands for assurance that quality care is being delivered. PMID- 1628567 TI - Deposition and dispersion of aerosols in the airways of the human respiratory tract: the effect of particle size. AB - Small volumes of aerosols (boluses) were inspired predominantly into the conducting airways of human lungs with a fast operating valve system, injecting preselected aerosol volumes near the end of a clean air inhalation. Particle recovery and bolus dispersion in the exhaled air after various periods of breathholding were investigated by measuring aerosol number concentration directly in front of the mouth with a laser photometer. Inspired and expired flow rates were measured with a pneumotachograph. The effect of particle size on these measurements has been investigated using aerosol particles with aerodynamic diameters (dae) between 0.9 and 5 microns. For aerosol particles smaller than 2 microns, bolus dispersion increases with increasing periods of breathholding (tb). After reaching a maximum, dispersion decreases with even longer tb. An increase in particle size yields a smaller increase in dispersion during the first seconds of breathholding while it is not changed significantly without breathhold. Particle losses during inhalation and exhalation increases with particle size. However, with increasing periods of breathholding, the losses of the smaller particles (less than 1.5 microns) were found to be much higher than expected theoretically, implying particle losses by sedimentation in the same airway structures. The small aerosol particles are deposited in smaller airways than bigger particles. These observations can be explained by cardiogenic mixing during periods of breathholding by pulsatile flow oscillations and confirm measurements with enhanced heart rate as described in an earlier paper. Small particles with restricted settling velocities remained longer in an airborne state in the airways and this leads to a more efficient cardiogenic mixing. PMID- 1628566 TI - Interactions between airway epithelium and mediators of inflammation. AB - Epithelial cells lining the respiratory airways classically are considered to be "target" cells, responding to exposure to a variety of inflammatory mediators by altering one or several of their functions, such as mucin secretion, ion transport, or ciliary beating. Specific responses of epithelial cells in vivo or in vitro to many of these inflammatory mediators are discussed. Recent studies have indicated that airway epithelial cells also can act as "effector" cells, responding to a variety of exogenous and/or endogenous stimuli by generating and releasing additional mediators of inflammation, such as eicosanoids, reactive oxygen species, and cytokines. Many of these epithelial-derived substances can diffuse away and affect neighboring cells and tissues, or can act, via autocrine or paracrine mechanisms, to affect structure and function of epithelial cells themselves. Studies dealing with airway epithelium as a source of inflammatory mediators and related compounds also are discussed. PMID- 1628568 TI - Intratracheal injection of crocidolite asbestos depresses the secretion of tumor necrosis factor by pleural leukocytes in vitro. AB - Tumor necrosis factor (TNF) is a cytokine released predominantly by monocytes/macrophages that has been shown to modulate a variety of different immune and metabolic functions. To understand the regulatory mechanisms of TNF in governing responses in the pleural cavity following deposition of fibrous dust in the airspace of the lung, we studied the capability of leukocytes, lavaged from the pleural cavity, to release TNF in culture. TNF production by lavaged pleural leukocytes was measured using the L-929 TNF-sensitive cell line, after intratracheal instillation of crocidolite asbestos. A high level of TNF activity was found in the supernatants of normal, unstimulated pleural leukocytes; the addition of 100 ng/ml lipopolysaccharide to the culture increased the activity up to threefold. Following intratracheal instillation of 5 mg crocidolite asbestos, the pleural leukocytes secreted less TNF than the control. With increasing mass of intratracheally instilled asbestos, there was a dose-dependent reduction in TNF release. Changes in the population of the pleural leukocytes or their number could not be related to variation in TNF activity. These results suggest that exposure of rat lungs to crocidolite asbestos by intratracheal instillation affects the response of pleural leukocytes without causing changes in the population. Such changes in the bronchoalveolar space may be related to the pleural pathology found in asbestos-exposed individuals. PMID- 1628569 TI - Particle transport through a hollow canine airway cast by high-frequency oscillatory ventilation. AB - High-frequency oscillatory ventilation (HFV) of the mammalian respiratory tract can maintain good respiratory ventilation, even with tidal volumes less than half of the anatomic dead space. A steady bidirectional drift is established in airways when the frequency is greater than 2 Hz, resulting in quasi-steady axial streams in the airways. Convective transport from the trachea to peripheral airways takes place in the central core of the bifurcating network of the bronchial tree. It takes place in the opposite direction in the annular regions near the airway walls. In this study, aerosol particle transport was measured in a hollow cast of a canine tracheobronchial tree that extended from the trachea to terminal bronchioles. The 0.5 micron particles, placed in the upper trachea as a bolus, were transported rapidly to the terminal airways of the cast by HFV with tidal volumes of less than one third the volume of the cast. Carrier gases of different kinematic viscosity were used to investigate the fluid dynamics of the transport. Particle transport during HFV was fastest in a gas of high kinematic viscosity (helium), and slowest in a gas of low kinematic viscosity (sulfur hexafluoride). The results are consistent with the application of lubrication theory, improve our understanding of convective processes involved in HFV, and provide new insights into particle penetration in the airways and other aspects of respiratory ventilation. PMID- 1628570 TI - Eprazinone alters lung lavage lipid levels and transtracheal ion transport. AB - Eprazinone therapy improves pulmonary function and arterial pO2 in patients with chronic bronchitis; however, the mechanism of action is unknown. The purpose of this study was to determine if eprazinone alters either lung surfactant levels in bronchoalveolar lavage fluid (BAL) of normal rats, or ion transport across canine tracheal epithelium mounted in Ussing chambers. In the surfactant studies, normal rats were force fed three doses (50, 100, and 200 mg/kg) of eprazinone for 4 days. Eprazinone at a dose of 200 mg/kg significantly increased total and individual (with the exception of phosphatidylinositol) phospholipid levels and decreased total neutral lipids. Lower doses of eprazinone significantly decreased neutral lipid levels without affecting the phospholipids. There was no change in BAL levels of protein or cells and no abnormal histology. In airway epithelial studies, mucosal addition of eprazinone produced a dose-dependent partially reversible decrease in short-circuit current (Isc). The decrease in Isc at lower eprazinone concentrations was accounted for entirely by a decrease in net chloride secretion while at higher concentrations both sodium and chloride transport were affected. Submucosal eprazinone had no affect on ion transport. These studies suggest that eprazinone influences both BAL lipid levels and ion transport, either of which could lead to a beneficial therapeutic effect. PMID- 1628571 TI - Changes of growth hormone, somatomedin C, and bombesin following pneumonectomy. AB - Left pneumonectomy (PX) was performed on 14-day-old pregnant rats. Serum growth hormone (GH), lung somatomedin-C-like immunoreactivity (SmC), and lung bombesin like immunoreactivity (BLI), using optimized radioimmunoassays and lung protein concentration (P), were measured 3 h, and 1, 2, 3, 5, and 7 days following pneumonectomy. These levels were compared to two groups of similar animals: sham operated animals and animals not subjected to surgery. Serum GH, lung SmC, and BLI levels were similar in the last two groups of animals, suggesting that surgery had no effect on GH, SmC, and BLI levels. These two control groups were combined and compared to the post-pneumonectomy animals. The post-pneumonectomy animals had significantly higher levels of serum GH at postoperative day 3 and significantly higher levels of SmC at days 2 and 5 without any significant difference in total BLI level and body weight. These results suggest that, first, GH and SmC may play a part in post-pneumonectomy compensatory lung growth and these two may also be interrelated in this response and, second, BLI material(s) perhaps do not play a role in post-pneumonectomy lung growth. PMID- 1628572 TI - Hierarchy of seizure states in the electrogenic limbic status epilepticus model: behavioral and electrographic observations of initial states and temporal progression. AB - Repeated electrical stimulation was delivered to the amygdala in a paradigm of electrogenic limbic status epilepticus induction in rats. We observed four distinct initial behavioral states associated with prolonged spiking, comprising an ordered hierarchy of severity: immobile, exploratory, minor convulsive, and clonic convulsive. The EEG and behavioral topography of the initial prolonged seizure state behaviorally and electrographically resembled the acute seizures that occurred earlier during induction. Onset of status epilepticus on limbic induction appears to represent not a new type of seizure activity, but instead the extended version of repeated brief limbic-onset seizures as seizure terminating mechanisms gradually become ineffective. These prolonged seizure states can therefore be used to study the anatomy and mechanisms of brief limbic seizures. We also examined the temporal progression of amygdala-induced prolonged seizure states. At one end of the severity spectrum, immobile-associated spiking was prone to terminate early, within 90 min, accompanied by normalization of behavior. At the other end of the spectrum, clonic convulsive status epilepticus slowly decreased in behavioral severity together with a change in EEG from fast to slow spiking. Exploratory status epilepticus was characterized by incessant explorationlike behavior that could last hours and was associated with slow periodic spike-complexes on EEG. The long-term course consisted either of slow devolution, with eventual cessation of spiking, or of spontaneous late ascension to convulsive status. Prolonged-seizure states may thus be considered to fall not only within an anatomic/behavioral hierarchy of severity, but also within a temporal physiologic progression. PMID- 1628573 TI - Differences of in vitro electrophysiology of hippocampal neurons from epileptic patients with mesiotemporal sclerosis versus structural lesions. AB - In vitro electrophysiologic studies of animal hippocampal slice models of epilepsy have generated hypotheses regarding cellular pathophysiologies associated with epileptogenesis. We tested some of these hypotheses using in vitro intracellular recordings of hippocampal neurons from patients with intractable temporal lobe epilepsy. We compared the electrophysiology of hippocampal neurons from 14 patients with mesiotemporal sclerosis with hippocampal neurons from 7 epileptic patients with structural lesions near the hippocampal biopsy. Both spontaneous and stimulus-evoked synaptic function and action potential firing patterns were observed. Presumed pyramidal neurons from sclerotic hippocampus were significantly less likely to display stimulus-evoked inhibitory postsynaptic potentials (IPSPs) and were more likely to fire spontaneously in bursts of action potentials than were hippocampal neurons from patients with structural lesions. No significant differences were detected in spontaneous postsynaptic potentials, spontaneous rhythmic synaptic events, spontaneous or anode break action potentials, stimulus-evoked excitatory postsynaptic potentials, or stimulus-evoked action potential bursts. Cellular membrane parameters were similar in the two groups, including resting membrane potential, action potential amplitude, action potential half-width, action potential threshold, input resistance, time constant, input/output relationship, and afterhyperpolarization amplitude. PMID- 1628574 TI - Increased pH and inorganic phosphate in temporal seizure foci demonstrated by [31P]MRS. AB - To investigate alterations of brain metabolism associated with temporal lobe epilepsy, [31P]MRS studies were performed on the anterotemporal lobes of patients with medically refractory complex partial seizures. Interictally, the pH was significantly more alkaline in the temporal lobe ipsilateral to the seizure focus (7.25 vs. 7.08, p less than 0.05), and the inorganic phosphorous concentration was greater on the side of the epileptogenic focus (1.9 vs. 1.1 mM, p less than 0.05). These changes in pH and inorganic phosphate may represent metabolic alterations secondary to seizures. Alternatively, because alkalosis enhances neural excitability and may enhance seizure activity, the increased pH of the seizure focus may provide insight into the pathophysiologic mechanism of epileptic seizures. PMID- 1628575 TI - Neuroimaging in temporal lobe epilepsy: test sensitivity and relationships to pathology and postoperative outcome. AB - We studied patients with documented temporal lobe seizures to evaluate the predictive value of computed tomography (CT), magnetic resonance imaging (MRI), and F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) for surgical therapy and the relationships between these tests and the pathologic diagnoses. CT detected abnormalities in 32.5%, with an accuracy of 19% when accuracy was defined as congruence with electrophysiologic studies. MRI detected abnormalities in 81%, with an accuracy of 67%. FDG-PET detected abnormalities in 85%, with an accuracy of 82%. Pathologic change was detected in 79% of the excised temporal neocortex, 65% of amygdalae, and 93% of hippocampi. After follow-up periods of 20 71 months (mean 41 months), 67% of patients were free of seizures and 94% had at least a 90% reduction in seizure frequency. There was no relationship between the type of abnormality on MRI or the type of pathology and postoperative outcome. Better outcomes were associated with focal or regional ictal onsets as recorded by surface EEG. Worse outcomes were associated with hypometabolism that extended outside the temporal lobe. Pathologic change in the temporal neocortex was associated with extension of hypometabolism outside the temporal lobe. PMID- 1628576 TI - Comparison of the intracarotid amobarbital procedure and interictal cerebral 18 fluorodeoxyglucose positron emission tomography scans in refractory temporal lobe epilepsy. AB - The relationship between interictal focal hypometabolism determined by 18 fluorodeoxyglucose positron emission tomography (FDG-PET) scans and memory function with the intracarotid amobarbital procedure (IAP) was evaluated in 23 patients with temporal lobe epilepsy. All patients underwent prolonged EEG/video monitoring. The epileptogenic focus was defined by interictal epileptiform discharges and ictal onsets. All 23 patients had recorded seizures arising exclusively from one temporal lobe. PET showed temporal lobe hypometabolism ipsilateral to the epileptogenic focus in 86% (20 of 23) of patients; IAP showed impaired memory of the hemisphere of seizure onset in 65% (15 of 23). Sixty-five percent (13 of 20) of patients with focal hypometabolism had ipsilateral memory impairment. Memory impairment contralateral to the hypometabolic zone was not observed. Ninety-five percent (22 of 23) of patients demonstrated functional impairment by either PET or IAP (or both) on the epileptogenic side. PMID- 1628577 TI - Long-term follow-up of stereotactic lesionectomy in partial epilepsy: predictive factors and electroencephalographic results. AB - We performed an extended follow-up study assessing the efficacy of stereotactic lesionectomy in 23 patients with foreign-tissue lesions and intractable partial epilepsy. Sixteen lesions involved functional or eloquent cortex as determined by anatomic localization. By definition, the surgical objective in these patients was excision of the lesion, and not the surrounding cerebral cortex. The mean duration of follow-up was 48.5 months (range 26-69 months). Seventeen patients (74%) had a significant reduction in seizures (greater than or equal to 90%) after lesionectomy. Thirteen patients (56%) had a class I operative outcome (seizure-free, single seizure episode, or auras only). Five of these patients were successfully discontinued from antiepileptic drug (AED) therapy. Patients with temporal lobe lesions were statistically less likely to be rendered seizure free (p less than 0.05). Age at operation, duration of epilepsy, and underlying pathology were not significant predictors of seizure outcome. The anatomic distribution of extracranial EEG recorded epileptiform activity did not appear to be an important determinant of outcome. The absence of interictal epileptiform activity in the 3-month postoperative EEG correlated with a significant reduction in seizures. Long-term follow-up indicates that lesionectomy may be effective in select patients with medically refractory partial seizure disorders. PMID- 1628578 TI - Prognosis of epilepsy in a rural African community: a 30-year follow-up of 164 patients in an outpatient clinic in rural Tanzania. AB - While working as a physician in Tanzania in the early 1960s, Dr. Louise Jilek Aall founded an outpatient clinic for epilepsy among the Pogoro people of Mahenge mountains where epilepsy (locally termed Kifafa) had brought misery and death to an unusually high percentage of the population. With local assistance and overseas donations of phenobarbital (PB), this clinic treated approximately 200 patients for less than or equal to 10 years. The area was revisited 30 years later to trace these patients. Of the 164 patients who had started treatment, 86 (52.4%) achieved complete seizure suppression, 59 (36.0%) experienced reduction in seizure frequency, 13 (7.9%) experienced no change, and in 1 (0.6%) seizures were worse. The effect of treatment could not be assessed in 5 (3.0%) patients. After 30 years, only 36 (21.9%) of the 164 patients were known to be alive. Of the patients, 110 (67.1%) had died, and the whereabouts of 18 (11%) could not be traced. The causes of death were epilepsy related (status epilepticus, drowning, burns, dying in or after a seizure) in greater than 50% of the patients. Epilepsy related deaths were proportionately higher after drug supply was stopped and among patients who were receiving drugs irregularly or who had only partial seizure control. Patients with epilepsy showed an increased mortality rate, which was twice that of the general rural Tanzanian population of similar age. Management of epilepsy in rural Africans should also emphasize methods to prevent epilepsy-related causes of death among patients with epilepsy. PMID- 1628579 TI - Psychosocial evaluation of adults with epilepsy in Chile. AB - The Washington Psychosocial Seizure Inventory (WPSI) was used to assess psychosocial functioning of 116 epileptic outpatients being treated in an epilepsy program at a public health service (PHS). Disturbances in several areas of psychosocial adjustment were noted. Although the distribution was similar to those previously reported using the WPSI, the severity of the observed disturbances was greater. Peak-score scales were Financial Status, Emotional and Interpersonal Adjustment, and Overall Psychosocial Functioning. Rehabilitation measures in epilepsy could play a substantial role in prevention and treatment of psychosocial disorders. PMID- 1628580 TI - Epileptic seizures in elderly patients with dementia. AB - All inpatients aged greater than 55 years with dementia in the Dundee Psychiatric Service were surveyed for seizure occurrence by interviewing staff and reviewing records. Of 208 patients, 19 (9.1%) were recorded as having seizures. The seizures were major in 92% and occurred at a rate of approximately 2.3 seizures per patient per year. Patients with epilepsy were significantly younger than a control group of dementia inpatients and were significantly more cognitively impaired on the survey Clifton Assessment Procedure for the Elderly (CAPE), but not on the Mini Mental State Examination. Of 111 reported accidents, only 5 appeared to be associated with epilepsy. Although epileptic seizures are relatively common in patients with severe dementia, they rarely caused severe problems. PMID- 1628581 TI - Classification of complex features of febrile seizures: interrater agreement. AB - As part of a prospective study of febrile seizures, three independent pediatric neurologists rated each of 100 febrile seizures for the presence of complex features: focality, long duration (greater than or equal to 10 min), and occurrence of multiple seizures. Seizure descriptions were assembled from all information available in the medical record and from a semistructured interview of a person who had witnessed the seizure. Interrater agreement assessed by kappa indicated excellent agreement with regard to whether the seizures were multiple or prolonged (kappa greater than or equal to 0.85) and fair to good agreement with regard to focality (kappa = 0.61-0.78). Disagreement occurred most often regarding assessment of focality. Reasons for disagreement included variation in interpretation of lateral eye deviation, staring episodes, and motor asymmetries in the context of a bilateral convulsion. PMID- 1628582 TI - Clinical manifestations in children with occipital spike-wave paroxysms. AB - The pattern of occipital-posterotemporal spike-wave paroxysms (O-PT SWPs), is a distinctive EEG abnormality observed primarily with occipital epilepsy of childhood and basilar artery migraine. We studied EEG and clinical features in 30 children and young adults with this EEG pattern. Prolonged and brief O-PT SWPs were observed. Prolonged discharges (greater than 6 s) were observed only in children with seizures (p less than 0.001), and brief discharges (1-6 s) were observed immediately after eye closure. Generalized SWPs (11 patients, 37%) and background abnormalities (17 patients, 57%) were common. Photic activation of O PT SWPs was not observed. Twenty-four patients (80%) manifested paroxysmal phenomena-seizures (20 patients, 67%) and migraine (12 patients, 40%, 4 alone and 8 with seizures). Fifteen patients (75%) had partial seizures, and 5 (25%) had absence seizures. In 7 patients with partial seizures, an etiology was evident. Neurologic examination was more often abnormal in patients with secondary partial seizures than in those with idiopathic partial seizures (p less than 0.05) and absence seizures. Conversely, migraine was more often associated with idiopathic partial seizures than with secondary partial seizures (p less than 0.05) and absence seizures. Six children (20%) had no paroxysmal events. Generalized SWPs were uncommon in patients with idiopathic partial seizures. We conclude that O-PT SWPs is a nonspecific epileptiform abnormality that may occur in children with (a) idiopathic partial, (b) symptomatic partial, and (c) absence epilepsies, but it may also occur in patients with no evidence of seizures. PMID- 1628583 TI - Controlled examination of effects of progressive relaxation training on seizure reduction. AB - We determined the efficacy of progressive muscle relaxation in reducing seizure frequency. Subjects were 24 people with epilepsy attending an urban neurology clinic. The experimental design consisted of an 8-week baseline period, a treatment period of six sessions of progressive relaxation training (PRT, n = 13) or quiet sitting (QS, n = 11) and an 8-week follow up. In the PRT group, 11 subjects reported a decrease in seizure frequency (p less than 0.01), and in the QS group, 7 reported a decrease (p greater than 0.05). The mean decrease in seizure frequency was 29% for the PRT group (p less than 0.01) but only 3% for the QS group (p greater than 0.05). This is the fifth recent report of a controlled study documenting the success of progressive relaxation therapy in seizure reduction. PRT is inexpensive and noninvasive and facilitates patient participation. Such a technique should be incorporated into clinical practice. PMID- 1628584 TI - Discontinuing medication in epileptic children: a study of risk factors related to recurrence. AB - We studied 70 children who had experienced at least two seizures before age 12 years, excluding febrile seizures, neonatal seizures, or seizures occurring during a metabolic, or infectious insult to the central nervous system (CNS) and who had been seizure free for at least 2 years. Twenty children (28.5%) experienced a recurrence, 75% during antiepileptic (AED) drug discontinuation or less than 6 months after discontinuation. Risk factors statistically related to seizure recurrence were greater than 10 seizures before seizure control, an abnormal EEG in the year before AED discontinuation, presence of focal neurologic signs and/or mental retardation, and presence of a mixed seizure pattern. Fourteen children (70%) with recurrence had two or more risk factors, whereas 36 (72%) without recurrence had no risk factor or only one. We conclude that a selected group of epileptic children who remain seizure-free for a period of at least 2 years can have AEDs discontinued based on presence or absence of risk factors. PMID- 1628585 TI - Daytime sleep tendency before and after discontinuation of antiepileptic drugs in preadolescent children with epilepsy. AB - In 9 preadolescent children treated for epilepsy who had been free from seizures long enough for treatment to be discontinued, daytime vigilance was studied before and after discontinuation of antiepileptic drugs (AEDs). Comparisons were made with healthy controls. Multiple sleep latency test (MSLT), EEG, and a questionnaire were used. As part of the analysis of the MSLT, a new measure, the daily average sleep tendency (DAST), was constructed to overcome the problems with data censoring of the classic MSLT analysis. The patients had significantly (p less than 0.001) higher daytime sleep tendency, even after drug discontinuation, than controls, a result that could neither be attributed to AED treatment nor to recent epileptic seizures or complicated epilepsy. PMID- 1628586 TI - External leakage from feeding gastrostomies in patients receiving valproate sprinkle. AB - We reviewed the incidence of external leakage from feeding gastrostomies in 8 patients who received valproate sprinkle (VPA-S). We also identified a control group of 31 children with feeding gastrostomies who were also cared for in our clinic, but who did not receive VPA-S. All patients in both groups have had their feeding gastrostomy greater than or equal to 6 months. Four of 8 children who received VPA-S through feeding gastrostomies developed problems with recurrent external leakage. The incidence of external leakage in our control group of children who had not received VPA-S was 2 in 31 (6.4%). We hypothesize that the external leakage is caused by adherence of the undissolved VPA-S particles to the exterior of the tube, preventing close approximation of the tube to the gastrostomy stoma. In most cases, VPA-S could continue to be administered and the problem of leakage reduced if the tubes were more frequently changed and/or a larger size were used. Complications with either leakage or occlusion were noted in all patients with the button feeding tube who had received VPA-S. Because of the especially high complication rate associated with administration of VPA-S in children with the "button" feeding tubes, we discourage VPA-S administration to children with that device. PMID- 1628588 TI - Interaction of the anticonvulsant ameltolide with standard anticonvulsants. AB - The newly characterized anticonvulsant ameltolide was studied in mice in combination with the standard antiepileptic drugs (AEDs), phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA). In combination with either PHT or CBZ, ameltolide produced dose-additive effects in the maximal electroshock (MES) test and in the horizontal screen (HS) test for neurologic impairment. The large separation between the doses for the anticonvulsant effects and the neurologically impairing effects (protective index, PI) were maintained as well in the combinations as in the individual compounds. VPA was impotent in the MES test and did not have a clear separation between the doses that produce the anticonvulsant effects and those that are neurologically impairing (low PI). When VPA and ameltolide were combined, the effects were less than additive by isobolographic analysis on both the MES and HS tests. At high oral doses (20 and 40 mg/kg, p.o.), ameltolide produced impairment on the HS test and decreased body temperature. The effects on the HS test were enhanced twofold, whereas the effects on body temperature were not markedly enhanced, by coadministration of the MES ED95 of PHT and CBZ. VPA (MES ED95) appeared to antagonize the temperature-lowering effects of ameltolide. These interaction studies suggest that ameltolide would be safe, with no unexpected effects, when used in epileptic patients concurrently receiving these standard AEDs. These studies also suggest that the effects of ameltolide would be lessened by simultaneous administration of VPA. PMID- 1628587 TI - Relation of plasma and brain concentrations of the anticonvulsant ameltolide to its pharmacologic effects. AB - Ameltolide, a newly described anticonvulsant, was studied to determine the relation between dose administered, plasma and brain concentrations, and pharmacologic effects. The relation of the N-acetyl metabolite and the OH-N acetyl metabolite to the dose administered and to the pharmacologic effects was also determined. Ameltolide plasma concentrations in both mice and rats were linearly related to dose administered over the entire dose range from low doses, at which the anticonvulsant effects were noted, to high doses, at which neurologic impairment occurred. The plasma concentrations of the metabolites were not as consistently linearly dose-related in the two species. In rats, the brain concentrations of ameltolide were highly correlated with plasma concentrations and the doses administered. Ameltolide was shown to have a phenytoin (PHT)-like anticonvulsant profile in vitro in the cortical slice preparation. These data confirm the potent anticonvulsant profile of ameltolide and the lack of significant activity of the metabolites. PMID- 1628589 TI - Phenytoin pharmacokinetics: before and after folic acid administration. AB - Phenytoin (PHT) exhibits linear and Michaelis-Menten pharmacokinetics. PHT decreases serum folate; the vitamin folic acid (FA) is hypothesized to be a cofactor in the metabolism of PHT. The depletion of serum folate may explain the unpredictability of measured total serum PHT concentrations and time to steady state as compared with the Michaelis-Menten predictive calculations. We examined PHT pharmacokinetics before and after FA supplementation in 13 healthy male volunteers. The study was divided into two phases. Phase I determined V(max) (mg/day) and Km (micrograms/ml) of PHT to calculate PHT doses needed for the second phase. Phase II was a four-way cross-over study to examine the effect of 1 and 5 mg FA on total serum PHT concentrations 1 microgram/ml less and 5 micrograms/ml greater than the subject's Km, Km - 1 and Km + 5, respectively. Predicted versus measured total serum PHT concentrations, t90% (days to steady state), and the effect of FA were calculated for Km - 1 and Km + 5 before and after 1 or 5 mg FA. The measured total serum PHT concentration was always greater than the calculated concentration (p less than 0.05), and t90% was always longer than the calculated t90% (p less than 0.05) for Km - 1 before FA (all subjects decreased serum FA); the same was observed for Km + 5. If folate is assumed to be a cofactor in PHT metabolism, these results are expected, because depletion of the vitamin would indicate less folate to drive the metabolism of PHT, resulting in higher total serum PHT concentrations and longer time to reach steady state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628590 TI - Fetal heart rate patterns and chronic exposure to antiepileptic drugs. AB - Fetal heart rate (FHR) characteristics of fetuses exposed and not exposed to antiepileptic drugs (AEDs) were studied. FHR is considered to reflect central nervous system (CNS) integrity. Three intervals during pregnancy were investigated: 20, 32, and 38 weeks. At 32 and 38 weeks, FHR was studied in relation to quiet (C1F) and active (C2F) sleep periods. For each tracing, a baseline was determined and accelerations and decelerations were identified. To assess FHR variability, the long-term irregularity, interval difference and absolute beat-to-beat indexes, and the bandwidth were calculated for 30-s intervals between accelerations and decelerations. No marked differences were noted between study and control groups concerning basal FHR and the occurrence of accelerations. For FHR derived from the fetal ECG, all indexes of FHR variability and the bandwidth were lower for the study group as compared with the control group, although the differences did not reach statistical significance. Our study shows that chronic prenatal exposure to AEDs does not seriously interfere with modulation of fetal heart rhythm by the CNS. PMID- 1628591 TI - Effect of antiepileptic drugs on growth of murine lymphoid tumor cells in single cell culture. AB - The effect of three commonly used antiepileptic drugs (AEDs), phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA), on the growth of lymphoid tumor cells was assessed in vitro. A single-cell culture method was used to determine growth rates by direct visualization. The amount of free drug was determined by ultrafiltration to ascertain its correlation to therapeutic drug levels. VPA slowed the growth of B-myeloma (FO) and T-lymphoma (AKR-1) cells significantly within the range of therapeutic drug levels. CBZ and PHT likewise inhibited cell growth in both lineages but at two to four times the therapeutic level of free drug. CBZ was shown to have long-term effects on FO and AKR-1 cells, demonstrated by the reduced growth rates of cloned lines for 2-3 months after drug removal. Cloned sublines of myeloma cells secreting lambda light chain (J558L) treated with CBZ or PHT had a higher frequency of lambda light chain secretion loss mutations than the nontreated parent line. PMID- 1628592 TI - Effect of valproate dose on formation of hepatotoxic metabolites. AB - Valproate (VPA) therapy has been associated with a rare but fatal hepatotoxicity. 4-ene-VPA and 2(E),4-diene-VPA, unsaturated metabolites of VPA, are hepatotoxins several times more potent than VPA. In a previous study, a dose-dependent excretion of hepatotoxic metabolites was noted in patients receiving VPA. Our study was designed to evaluate the effect of dose on VPA metabolism under controlled conditions. Nineteen healthy volunteers sequentially received three different daily doses of VPA (250, 500, and 1,000 mg). Each dose was given twice daily for 4 days. Urine was collected for one dosage interval (12 h) at steady state for each dose and assayed for 15 VPA metabolites by gas chromatography/mass spectrometry (GCMS). Blood samples were also obtained from eight of the subjects, and VPA was assayed by GCMS. No effect of dose was noted on total plasma clearance. There was a significant dose-dependent decrease in intrinsic hepatic clearance. The intrinsic formation clearance (Clf) of the 4-ene-VPA pathway showed a statistically significant dose-dependent increase (0.22, 0.33, 0.40 ml/h/kg). The corresponding percentage of dose recovered as 4-ene-VPA and its sequential metabolites showed significant dose-dependent increases (0.15, 0.27, 0.62%). The role of VPA dose in the pathogenesis of hepatotoxicity may be more important than was previously believed. PMID- 1628593 TI - Effects of valproate in a model nervous system (buccal ganglia of Helix pomatia): I. Antiepileptic actions. AB - Cellular actions of valproate (VPA) were studied using intracellular recordings of identified neuronal individuals in the buccal ganglia of Helix pomatia. Under nonepileptic conditions, VPA induced (a) a hyperpolarization, (b) slight changes in action potentials (AP), and (c) an increase in membrane resistance. Under epileptic conditions (i.e., during application of an epileptogenic drug), extracellular application of VPA decreased frequency of occurrence of epileptic depolarizations (early effect) and led to a decay in paroxysmal depolarizations (late effect). Intracellular injection of VPA could block epileptic activity in the treated neuron immediately. A metabolite of VPA (trans-2-en VPA) mainly lacked the late effect (decay in epileptic depolarizations) obtained with VPA. Results suggest that the early antiepileptic effect is exerted from the extracellular side of the neuronal membrane and that the late effect results from intracellular actions of VPA being delayed by slow access to an intracellular site. PMID- 1628594 TI - Effects of valproate in a model nervous system (buccal ganglia of Helix pomatia): II. Epileptogenic actions. AB - High concentrations of valproate (VPA; greater than 20 mM) depolarized identified neuronal individuals in the buccal ganglia of Helix pomatia and transiently induced paroxysmal depolarization shifts (PDS). Threshold concentration of VPA for the induction of PDS was decreased (a) by increased seizure susceptibility, (b) by increased concentrations of derivatives of VPA, and (c) by increased H+ concentrations. Intrasomatic injection of VPA did not induce PDS. The epileptogenic action of VPA is believed to be exerted from the extracellular side of the cell membrane. PMID- 1628596 TI - Immobilized pH gradients (IPG) PMID- 1628595 TI - Dihydropyridine calcium antagonists in mice: blood and brain pharmacokinetics and efficacy against pentylenetetrazol seizures. AB - Dihydropyridine calcium antagonists are candidate anticonvulsants, but little is known of their penetration into brain. Nifedipine (NFD) and nimodipine (NMD) pharmacokinetics were compared in mouse blood and brain, and their activity against pentylenetetrazol (PTZ) was assessed. After intraperitoneal (i.p.) injection, both dihydropyridines achieved peak blood and brain concentrations in 5 min. Estimated blood and brain elimination half-lives (t1/2) of NMD (16.7 and 22.4 min) were slightly longer than those of NFD (11.2 and 14.7 min). Brain and blood concentrations correlated with both NFD (r = 0.701, p less than 0.001) and NMD (r = 0.572, p less than 0.001). Injection of the dihydropyridines as a suspension (Tween 80) did not alter brain penetration, although systemic absorption was more erratic. NFD (p less than 0.001), NMD (p less than 0.02), and carbamazepine (CBZ, p less than 0.001) i.p. inhibited PTZ-induced seizures. Brain concentrations of PTZ were not altered by NFD pretreatment. Combining NFD and CBZ was less effective than giving NFD alone (p less than 0.005). NFD (p less than 0.002) and NMD (p less than 0.001) inhibited PTZ seizures after 2-week oral dosing, but low dosing was more effective than high dosing (p less than 0.002). NFD and NMD cross the blood-brain barrier (BBB) in mice and inhibit PTZ seizures. A possible therapeutic window was identified, and NFD and CBZ were less effective in combination than singly. A pharmacodynamic interaction may exist, inhibiting effective use of dihydropyridines as adjunctive therapy in epileptic patients. PMID- 1628597 TI - The Immobiline family: from "vacuum" to "plenum" chemistry. AB - We list here a total of 17 acrylamido acids and bases as potential buffers and titrants for isoelectric focusing separations in immobilized pH gradients. The chemistry of these compounds is reviewed and general guidelines are given for their proper use. In particular, it is shown that the most delicate compounds are the basic species, since they can undergo several degradation pathways, including: (i) spontaneous hydrolysis to acrylic acid and a diamine; (ii) spontaneous autopolymerization to oligomers and n-mers; (iii) oxidation to N oxides during the persulfate polymerization step. A hydrophobicity scale has been constructed, by partitioning the deprotonated species in water/1-octanol phases. A scale of resistance to alkaline hydrolysis for the basic acrylamido buffers is also given, followed by general consideration on the structure/stability relationship of these chemicals. PMID- 1628598 TI - Two-dimensional polyacrylamide gel electrophoresis, with immobilized pH gradients in the first dimension, of barley seed proteins: discrimination of cultivars with different malting grades. AB - The suitability of high-resolution two-dimensional gel electrophoresis for barley cultivar discrimination and for classification with respect to their malting properties was studied. Seed proteins of 14 barley cultivars with different malting qualities were extracted with urea/dithiothreitol/Nonidet P-40 buffer and subjected to two-dimensional gel electrophoresis with immobilized pH gradients in the first dimension (IPG-DALT). The results of IPG-DALT were compared to the protein patterns obtained by a standard technique, sodium dodecyl sulfate polyacrylamide gel electrophoresis of hordeins. Sodium dodecyl sulfate-gel electrophoresis yielded seven different "B" and four different "C" hordein patterns; "A" and "D" hordein patterns were uniform in all cultivars tested. Four cultivars could be distinguished unequivocally, the others were classified into three groups containing between two and five cultivars. In contrast to these findings. IPG-DALT yielded three different "A", eight different "B", four different "C" and two different "D" hordein patterns. When the "A", "B", "C" and "D" hordein patterns were combined, ten cultivars exhibited unique hordein patterns whereas the remaining ones were classified into two groups containing two cultivars each. Moreover, when albumin and globulin proteins were used for evaluation in addition to the hordeins, all cultivars could be discriminated by IPG-DALT. IPG-DALT, performed on small-scale and/or ready-made gels, proved to be an ideal complementary system to one-dimensional electrophoretic methods for routine seed testing purposes because of its speed, reliability, and simplicity. IPG-DALT was also applied to study the relationship between the different polypeptide patterns and the malting quality. Although cultivars with identical one-dimensional protein patterns but different malting quality could be successfully differentiated by IPG-DALT, a direct correlation between specific protein spots or protein patterns to the malting quality was not found within the cultivars tested. PMID- 1628599 TI - Monitoring by two-dimensional electrophoresis somatic embryogenesis in leaf and petiole explants from Vitis. AB - A two-dimensional electrophoretic analysis of the total proteins was carried out in Vitis rupestris as model system in order to characterize the different developmental stages--from callus to plantlets--of somatic embryogenesis events in the grapevine. The patterns of callus, embryogenetic callus, somatic embryos and plantlets derived from leaf and petiole explants were compared. Each differentiation step was characterized by specific peptide spots. PMID- 1628600 TI - Immobilized pH 2.5-11 gradients for two-dimensional electrophoresis. AB - Extremely wide immobilized pH gradients, pH 2.5-11, for isoelectric separation of complex protein mixtures are described. These pH gradients are theoretically and practically the maximum that can be achieved at present with the available acrylamido buffers and titrants. Conditions are described for reducing conductivity and electroendosmosis in extreme pH ranges. Furthermore, new conditions are described for the separation of proteins in the second dimension. Using this protocol, nearly all the possible cellular products can be separated in one single two-dimensional map. PMID- 1628601 TI - Analysis of recombinant proteins by isoelectric focusing in immobilized pH gradients. AB - Isoelectric focusing in immobilized pH gradients (IEF-IPG) was used to analyze three different recombinant proteins. Recombinant leech hirudin (65 amino acids, three disulfide bonds) expressed in Saccharomyces cerevisiae as a secreted protein and purified by anion-exchange and reversed-phase chromatography proved to be homogeneous with regard to its isoelectric point (pI). In addition, the theoretical pI, calculated on the basis of the primary structure, corresponded precisely to the measured pI of 4.30. IEF-IPG was further employed to follow the stability of recombinant hirudin at pH 9, indicating that deamidation occurred under these conditions. A variant of recombinant human alpha 1-antitrypsin (AAT) (389 amino acids, one cysteine residue) expressed in Escherichia coli and purified by anion-exchange, metal chelate and hydrophobic-interaction chromatography appeared to be homogeneous by polyacrylamide gel electrophoresis under reducing and denaturing conditions as well as by various high performance liquid chromatography methods. However, some heterogeneity was detected by IEF IPG between pH 5-6. The measured pI values of 5.43-5.58 were slightly lower than the calculated pI based on the primary structure (5.72). This indicated deamidations of Asn or Gln residues. A recombinant Schistosoma mansoni parasite antigen, p28 (210 amino acids, one cysteine residue) obtained after intracellular expression in Saccharomyces cerevisiae and affinity purification on glutathione agarose was analyzed by IEF-IPG in a pH 7.3-8.3 gradient. It appeared to be heterogeneous with regard to its pI, with the major component having a pI of 7.81 compared to the calculated value of 7.17.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628602 TI - Direct detection of carrier ampholytes in immobilized pH gradients using picric acid precipitation. AB - A protocol is described for monitoring the heterogeneity of end products of organic syntheses yielding amphoteric molecules containing two or more amino groups. This protocol was found to be a valuable aid in synthesis of carrier ampholytes for specific isoelectric focusing applications. This method does not depend on the ampholytes themselves to dictate the conditions under which they are analyzed. Carrier ampholytes have been found previously to be insoluble in picric acid and the insolubility property was not dependent upon the pI of individual ampholyte species. This insolubility property was exploited in the protocol. Immobilized pH gradients were used to focus the carrier ampholytes. Ampholytes were then visualized in situ by picric acid precipitation. The data shows that the protocol is useful for analyzing the results of chemical manipulations for enhancing the resolution of carrier ampholytes. A direct relationship was shown between carrier ampholyte heterogeneity as demonstrated by this protocol and the resolution of complex protein mixtures in isoelectric focusing gels. Picric acid formed visible precipitates with a variety of organic compounds which contained more than one amino group. PMID- 1628603 TI - Carbohydrate analysis of transferrin subfractions isolated by preparative isoelectric focusing in immobilized pH gradients. AB - Analytical isoelectric focusing of human serum transferrin has revealed the presence of up to nine different transferrin subfractions. The less prevalent subfractions have hitherto not been available for analytical work on their composition. Prolonged isoelectric focusing in immobilized pH gradients is capable of effectively separating and concentrating these subfractions from other fractions that are often present in over 70-fold excess in native preparations. Preliminary results of the carbohydrate analysis indicate a heterogeneity extending beyond the present concepts of the transferrin glycan structure. PMID- 1628604 TI - The use of immobilized pH gradients for the detection of human polymorphisms in the forensic identification of bloodstains. AB - Some polymorphic proteins (alpha 1-antitrypsin, orosomucoid, transferrin, group specific component, plasminogen) and enzymes (phosphoglucomutase, acid phosphatase, estrase D) were determined in bloodstain extracts by isoelectric focusing with carrier ampholytes (CA) and with immobilized pH gradients (IPGs) rehydrated with CA. IPGs yield superior results for typing of genetics markers in bloodstains since phenotypes are better distinguished and the bands are straighter and sharper in the presence of contaminants. Also, the sensitivity of IPGs with CA is similar to isoelectric focusing (IEF) with CA. A new variant, ACP*B1, found in Negroid west African populations and not found in Caucasians is described. Such a variant can only be determined by IPGs since its isoelectric point (pI 5.95) is close to that of the ACP*B (pI 6.05) variant. PMID- 1628605 TI - Studies on an apolipoprotein C-II variant occurring in Caucasians. AB - Apolipoproteins C (apo C-II, apo C-III0, apo C-III1 and apo C-III2) from delipidated very low density lipoproteins (VLDL) of 522 normo- and hyperlipoproteinemic Caucasians were screened by analytical isoelectric focusing. The immobilized pH gradient used was pH 4.0-5.0 with 7 M urea, which raised the apparent pH range to 4.8-5.7. As identified by immunoblotting, six unrelated persons had two major isoforms of apo C-II, the normal apo C-II-1 (which focuses between apo C-III0 and apo C-III1) and a variant, designated apo C-II-v according to Huff et al., focusing between apo C-III1 and apo C-III2 due to a more acidic pI. In narrow pH gradients, apo C-II-v can readily be discriminated from the minor isoform, apo C-II-2, due to its slightly more basic pI, corresponding to a difference of 0.01 pH units. Neuraminidase treatment did not alter the pI of apo C-II-v and on two-dimensional electrophoresis the molecular weights of apo C-II-1 and apo C-II-v were indistinguishable. The frequency of apo C-II-v was 1.2%. It was the same in males and females and was independent of hypertriglyceridemia. The autosomal codominant inheritance could be demonstrated in the pedigree of one family. Electroblotting of apo C-II-1 and apo C-II-v onto activated glass fiber sheets, followed by amino acid sequence analysis of the amino terminal ends, revealed an exchange of the amino acid lysine at position 19 by threonine in apo C-II-v.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628606 TI - Apolipoprotein E phenotyping by isoelectric focusing in immobilized pH gradients and silver staining. AB - A simple and high resolution procedure of apoprotein E (apo E) phenotyping by isoelectric focusing with immobilized pH gradients and silver staining is described. This method needs delipidated very low density lipoproteins (isolated from 1 mL of serum) but obviates immunoblotting as well as neuraminidase treatment in routine applications because the sialylated forms are clearly separated. Immunoblotting (with polyclonal and monoclonal anti-apo E antiserum), cysteamine and neuraminidase treatment, and pI markers allowed the localization of three main alleles, xi 2, xi 3, xi 4 and the detection of variants or rare alleles (6/450 determinations). The serum amyloid A (SAA) apolipoproteins (SAA1,SAA2) could be characterized unequivocally (especially with E3 and E4). Silver staining proved more sensitive than Coomassie Brilliant Blue and needs only 5 micrograms of protein in the sample. The results of 403 normo-or hyperlipidemic patients are shown. In the group of 191 normolipidemic patients (cholesterol less than 6.40 mmol/L triglycerides less than 2 mmol/L), the relative frequency of the xi 3 allele (0.83) is higher than in other reports on Caucasians (about 0.77) whereas the xi 4 allele is lower. As previously described, we find a high frequency of the 4/3 phenotype in hypercholesterolemia and 3/2 in hypertriglyceridemia. The high frequency of the E2/E2 phenotype, usually associated with hyperlipidemia, and variants in complex hypertriglyceridemia makes the apo E phenotyping necessary in many cases of dyslipidemias. PMID- 1628607 TI - Microheterogeneity of apolipoprotein D as revealed by electroblotting following isoelectric focusing in Immobiline DryPlates. AB - The microheterogeneity of apolipoprotein D was examined by a procedure involving, in sequences: (i) electrophoresis in an immobilized pH 4-7 gradient in an Immobiline DryPlate-polyacrylamide gel supplemented with Ampholine pH 5-7, (ii) covering of the gel with sodium dodecyl sulfate-containing agarose, (iii) electroblotting onto a polyvinylidene difluoride membrane and (iv) immunological identification. Seven isoforms were obtained with partially purified apolipoprotein D. Using this technique the apparent pI values at 15 degrees C for the isoforms were 4.57, 4.67, 4.78, 4.83 and 5.95, 6.06 and 6.19 (SD +/- 0.05 for all). Direct staining of the Immobiline DryPlate could not reveal the isoforms of partially purified apolipoprotein D. PMID- 1628608 TI - Modified silver staining for immobilized pH gradients. AB - Silver development of gels containing an immobilized pH gradient has proved difficult so far because the bonded buffers (especially the tertiary amino acrylamido derivatives) tend to absorb silver ions with a resultant heavy background of increasing darkness from the anode to the cathode. We report a variant of silver staining in which thiosulfate is used twice: (i) prior to silver impregnation, at the millimolar level, to enhance sensitivity, and (ii) during development, at the micromolar level, to decrease the background. PMID- 1628609 TI - Gain effects on performance using a head-controlled computer input device. AB - The purpose of this study was to use a Fitts' task to (1) determine how control display gain influences performance using a head-controlled computer input device; (2) compare relative sensitivity to gain and optimal gain between head control and hand/arm control; and (3) investigate control-display gain interactions with other task factors including target width, movement amplitude and direction. The task was a discrete target acquisition task using circular targets of 2.9 mm, 8.1 mm, and 23.5 mm, movement amplitudes of 24.3 mm and 61.7 mm, and eight radial directions including 0 degrees, 45 degrees, 90 degrees, 135 degrees, 180 degrees, 225 degrees, 270 degrees, and 315 degrees. Each device was operated at four gain levels. Ten subjects participated. The results indicated that gain had a significant effect on movement time for both types of pointing devices and exhibited local minimums. Discrete target acquisition at all gains was aptly described using Fitts' Law for both input devices. The mouse gain resulting in minimum movement time and RMS cursor deviation was between 1.0 and 2.0. The minimum movement time and RMS cursor deviation for the head-controlled pointer occurred at a gain between 0.3 and 0.6. Average movement time at the optimal head-controlled pointer gain had a slope of 169 ms/bit and was more than 76% greater than at the optimal mouse gain with a slope of 135 ms/bit. In addition, average RMS displacement was more than 27% greater for the head controlled pointer at its optimal gain setting than for the mouse. Gain had the greatest effect for small target widths and long movement amplitudes using the head-controlled pointer. Average movement time increased 37% when increasing the head-controlled pointer gain from 0.6 to 1.2 for the small target width, but only increased 0.3% when increasing gain for the large target width. Average movement time also increased 12% when decreasing the head-controlled pointer gain from 0.3 to 0.15 for the long movement amplitude, but decreased 0.3% when decreasing gain for the short movement amplitude. PMID- 1628610 TI - Higher rate of evolution of X chromosome alpha-repeat DNA in human than in the great apes. AB - The rate of introduction of neutral mutations is lower in man than in other primates, including the chimpanzee. This species is generally regarded as our closest relative among the great apes. We present here an analysis of sequences of X chromosomal alphoid repetitive DNA from man and the great apes, which supports the closer relationship between man and chimpanzee and indicates a considerably increased rate of recombination in the human repeat DNA. These results indicate that the 'molecular clock' is running more quickly in man. PMID- 1628611 TI - Three-dimensional structure of transketolase, a thiamine diphosphate dependent enzyme, at 2.5 A resolution. AB - The crystal structure of Saccharomyces cerevisiae transketolase, a thiamine diphosphate dependent enzyme, has been determined to 2.5 A resolution. The enzyme is a dimer with the active sites located at the interface between the two identical subunits. The cofactor, vitamin B1 derived thiamine diphosphate, is bound at the interface between the two subunits. The enzyme subunit is built up of three domains of the alpha/beta type. The diphosphate moiety of thiamine diphosphate is bound to the enzyme at the carboxyl end of the parallel beta-sheet of the N-terminal domain and interacts with the protein through a Ca2+ ion. The thiazolium ring interacts with residues from both subunits, whereas the pyrimidine ring is buried in a hydrophobic pocket of the enzyme, formed by the loops at the carboxyl end of the beta-sheet in the middle domain in the second subunit. The structure analysis identifies amino acids critical for cofactor binding and provides mechanistic insights into thiamine catalysis. PMID- 1628612 TI - Mutations of Ha-ras p21 that define important regions for the molecular mechanism of the SDC25 C-domain, a guanine nucleotide dissociation stimulator. AB - The SDC25 C-domain is a very active guanine nucleotide dissociation stimulator (GDS) isolated from Saccharomyces cerevisiae which acts equally well on Ha-ras p21 and yeast RAS2. These properties make the SDC25 C-domain a suitable tool to study the basic mechanism of a GDS. The action of the SDC25 C-domain was analysed by mutation of structurally important regions of p21. Substitutions that influence the coordination of Mg2+.GDP or the interaction of the guanine ring were found to stimulate the intrinsic dissociation of GDP and suppress the action of the SDC25 C-domain. No relevant effects were observed with mutations in the phosphate binding loop L1 or by deleting the last 23 C-terminal residues of p21. Substitutions in the switch region 1 (loop L2) and 2 (loop L4) of p21 strongly impaired the action of this GDS; however, we show that this effect is not related to a decreased affinity of the SDC25 C-domain for the mutated p21. No functional competition could be found between this GDS and the catalytic domain of the human GTPase activating protein (GAP). This indicates that GDS and GAP bind to different sites of the p21.nucleotide complex, even though the same mutations in loops L2 and L4 regions affect the activity of both effectors. Since these two regions appear not to be involved directly in the interaction with GDS, we conclude that the negative effect induced by their mutation is related to their function as switches of selective conformations during the GDP to GTP exchange reaction catalysed by GDS. PMID- 1628613 TI - Evidence for the presence of a secondary structure at the dibasic processing site of prohormone: the pro-ocytocin model. AB - Bioactivation of pro-proteins by limited proteolysis is a general mechanism in the biosynthesis of hormones, receptors and viral protein precursors. This proceeds by cleavage of peptide bonds at the level of single or pairs of basic residues in the proforms. Examination of a number of cleavage loci in various precursors failed to reveal any consensus primary sequence around the dibasic cleavage sites. Thus it has been proposed, on the basis of secondary structure predictions [Rholam, M., Nicolas, P. and Cohen, P. (1986) FEBS Lett., 207, 1-6], that those basic residues which operate as signal loci for the proteolytic enzyme machinery are situated in, or next to, privileged precursor regions most often constituted by flexible and exposed motifs, e.g. beta-turns and/or loops. Peptides reproducing the N-terminal processing domain of the hormone precursor, pro-ocytocin-neurophysin, were examined by a combination of spectroscopical techniques including circular dichroism, infrared Fourier transform and one- and two-dimensional proton NMR. The results indicate that: (i) the region situated on the N terminus of the Lys-Arg doublet is organized as a beta-turn in solution; (ii) the sequential organization of the residues participating in the beta-turn determines the privileged relative orientation of the basic amino acid side chains and the subtype of turn; (iii) the peptide segment situated on the C terminal side of the dibasic, corresponding to the N-terminal octapeptide of neurophysin, is organized as an alpha-helix.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628614 TI - Influenza virus hemagglutinin with multibasic cleavage site is activated by furin, a subtilisin-like endoprotease. AB - Many viruses have membrane glycoproteins that are activated at cleavage sites containing multiple arginine and lysine residues by cellular proteases so far not identified. The proteases responsible for cleavage of the hemagglutinin of fowl plague virus, a prototype of these glycoproteins, has now been isolated from Madin-Darby bovine kidney cells. The enzyme has a mol. wt of 85,000, a pH optimum ranging from 6.5 to 7.5, is calcium dependent and recognizes the consensus sequence R-X-K/R-R at the cleavage site of the hemagglutinin. Using a specific antiserum it has been identified as furin, a subtilisin-like eukaryotic protease. The fowl plague virus hemagglutinin was also cleaved after coexpression with human furin from cDNA by vaccinia virus vectors. Peptidyl chloroalkylketones containing the R-X-K/R-R motif specifically bind to the catalytic site of furin and are therefore potent inhibitors of hemagglutinin cleavage and fusion activity. PMID- 1628615 TI - Protein synthesis inhibitors differentially superinduce c-fos and c-jun by three distinct mechanisms: lack of evidence for labile repressors. AB - Protein synthesis inhibitors strongly augment and prolong the usually transient induction of c-fos and c-jun by growth factors, phorbol esters etc., a phenomenon termed superinduction which is conventionally regarded as a secondary consequence of translational arrest. Our recent demonstration that some inhibitors can act positively as nuclear signalling agonists compromises this view and necessitates a re-evaluation of superinduction. First, we show that labile repressors, widely postulated to act negatively on diverse superinducible genes, are not involved in regulating c-fos and c-jun. Secondly, two components of c-fos and c-jun superinduction, namely the delay in shutting off transcription and stabilization of their mRNAs, arise from translational arrest and are common to all protein synthesis inhibitors. Thirdly, the recently described capacity to act positively as nuclear signalling agonists to stimulate pp33/pp15 phosphorylation is restricted to compounds such as anisomycin and cycloheximide; these, but not emetine or puromycin, will induce c-fos/c-jun on their own. Fourthly, the translational arrest-related components of superinduction are dissociable from the signalling agonist effects at sub-inhibitory concentrations of anisomycin, under which conditions a new type of c-fos/c-jun superinduction with 'spike' kinetics is observed. Finally, we show that in response to EGF plus anisomycin, the nuclear signalling responses are themselves augmented and prolonged in a manner that corresponds to c-fos/c-jun superinduction under these conditions. PMID- 1628616 TI - OCH1 encodes a novel membrane bound mannosyltransferase: outer chain elongation of asparagine-linked oligosaccharides. AB - The Saccharomyces cerevisiae och1 mutant shows a deficiency in the mannose outer chain elongation at the non-permissive temperature. We have cloned the OCH1 gene by complementation of temperature sensitive (ts) phenotype for growth. The integrant of OCH1 gene in the yeast chromosome can complement the ts phenotype and shows the same mapping position as that of the och1 mutation, indicating that the cloned gene is the true gene for mutation. The OCH1 gene disruptant is not lethal but ts for cell growth, and lacks mannose outer chains. The OCH1 gene sequence predicts a 55 kDa protein consisting of 480 amino acids. It contains four potential asparagine-linked (N-linked) glycosylation sites and a single transmembrane region near the N-terminus. In vitro translation/translocation analysis revealed that the large C-terminal region of the OCH1 protein is located at the lumenal side of microsomal membranes with some sugar modification, indicating a type II membrane topology. The OCH1 protein was detected in yeast membrane fractions as four forms of 58-66 kDa, which correspond to the size of a glycoprotein containing four N-linked sugar chains the length of which is almost the same or slightly larger than the inner core (Man8GlcNAc2) formed in the endoplasmic reticulum (ER). Finally, the OCH1 gene was found to encode a novel mannosyltransferase which specifically transfers [14C]mannose to the unique acceptor, the core-like oligosaccharide of cell wall mannan accumulated in the och1 disruptant. PMID- 1628617 TI - Amphiphysin, a novel protein associated with synaptic vesicles. AB - To obtain access to novel proteins of the neuronal synapse, we have raised antisera against proteins of synaptic plasma membranes and used them for immunoscreening brain cDNA expression libraries. One of the newly isolated cDNAs encodes an acidic protein of 75 kDa with a distinct architecture of structural domains and multiple potential phosphorylation sites. Light and electron microscopy employing monospecific antisera raised against the expression product indicate a synapse-specific, presynaptic localization of this protein in many synapses of the chicken and rat nervous system. Its overall distribution in brain is very similar to that of synaptophysin, a ubiquitous protein of synaptic vesicles. In addition to brain, the protein or its mRNA is expressed in adrenal gland and anterior and posterior pituitary, but was not detected in a variety of other tissues. In controlled pore glass chromatography the native protein copurifies with synaptic vesicles and largely remains associated with them under various washing conditions. However, its amino acid sequence is very hydrophilic and it segregates into the aqueous phase in detergent phase partition. An earlier step of synaptic vesicle purification, sucrose cushion centrifugation, separates a vesicle-bound fraction of this protein from an unbound fraction. This seems to be a new, perhaps peripheral, protein of synaptic vesicles for which we propose the name, amphiphysin. PMID- 1628618 TI - Giant lens, a gene involved in cell determination and axon guidance in the visual system of Drosophila melanogaster. AB - Mutations in the Drosophila gene giant lens (gil) affect ommatidial development, photoreceptor axon guidance and optic lobe development. We have cloned the gene using an enhancer trap line. Molecular analysis of gil suggests that it encodes a secreted protein with an epidermal-growth-factor-like motif. We have generated mutations at the gil locus by imprecise excision of the enhancer trap P-element. In the absence of gil, additional photoreceptors develop at the expense of pigment cells, suggesting an involvement of gil in cell determination during eye development. In addition, gil mutants show drastic effects on photoreceptor axon guidance and optic lobe development. In wildtype flies, photoreceptor axons grow from the eye disc through the optic stalk into the larval brain hemisphere, where retinal innervation is required for the normal development of the lamina and distal medulla. The projection pattern of these axons in the developing lamina and medulla is highly regular and reproducible. In gil, photoreceptor axons enter the larval brain but fail to establish proper connections in the lamina or medulla. We propose that gil encodes a new type of signalling molecule involved in the process of axon pathfinding and cell determination in the visual system of Drosophila. PMID- 1628619 TI - Brain 4: a novel mammalian POU domain transcription factor exhibiting restricted brain-specific expression. AB - The POU domain gene family of transcription factors share a conserved bipartite DNA binding domain, and exhibit distinct temporal and spatial patterns of expression during development, particularly in the forebrain. A cDNA encoding a new member of the POU-III class of the POU domain gene family, referred to as Brn 4, was isolated from a rat hypothalamic cDNA library. Like other mammalian POU III genes previously characterized (Brn-1, Brn-2, Tst-1), Brn-4 transcripts are initially widely expressed at all levels of the developing neural tube, but in contrast to other previously described POU-III genes, are subsequently restricted to only a few regions of the adult forebrain, including the supraoptic and paraventricular nuclei of the hypothalamus. Brn-4 was shown to bind to DNA sequences containing the octamer motif and to trans-activate promoters containing this DNA binding motif, based on the actions of a unique N-terminal information. This ontogenic pattern of Brn-4 expression in concert with that of Oct-2 and Pit 1, indicates that certain POU domain genes potentially exert their primary functions widely during early neural development, and in a very limited set of neurons in the mature brain. PMID- 1628620 TI - Mutually exclusive expression of a helix-loop-helix gene and N-myc in human neuroblastomas and in normal development. AB - We have isolated a novel human gene encoding a helix-loop-helix (HLH) protein by molecularly cloning chromosome 1p36-specific CpG islands. The gene termed heir-1 was localized to the neuroblastoma consensus deletion at 1p36.2-p36.12. Its predicted protein is 95.8% identical to the mouse HLH462 protein and has clear homology to the mouse Id and Drosophila emc proteins. Heir-1 does not encode a basic DNA binding domain as found in basic HLH proteins. The gene is expressed specifically at high abundance in adult lung, kidney and adrenal medulla, but not in adult brain. Despite prominent heir-1 expression in adrenal medulla, which is a prime target for neuroblastomas, 10 out of 12 neuroblastoma-derived cell lines revealed very low levels of heir-1 mRNA. Low heir-1 expression was generally found in tumor cell lines with N-myc overexpression, whereas the two cell lines displaying high heir-1 levels did not overexpress N-myc. Mutually exclusive expression of both genes was also found by in situ hybridization in developing mouse tissues, particularly in the forebrain neuroectoderm. We conclude that heir 1 expression is reduced specifically in the majority of neuroblastomas and suggest an inverse correlation between heir-1 and N-myc expression in neuroblastoma tumors and in embryonic development. PMID- 1628621 TI - Transcription factor AP-2 activates gene expression of HTLV-I. AB - The HTLV-I LTR contains three conserved regulatory elements known as 21 base pair repeats which are required for stimulation of gene expression by the transactivator protein tax. Mutagenesis indicates that the 21 bp repeats can be subdivided into three motifs, A, B and C, each of which influences the level of tax activation. The A site in the 21 bp repeat has strong homology with previously described binding sites for the transcription factor AP-2. We demonstrated that AP-2 mRNA was present in T-lymphocytes and that cellular factors from both non-transformed and transformed T-lymphocytes specifically bound to the consensus motif for AP-2 in each 21 bp. To determine the role of AP 2 in the regulation of the HTLV-I LTR gene expression, we used an AP-2 cDNA in DNA binding and transient expression assays. Gel retardation and methylation interference studies revealed that bacterially produced AP-2 bound specifically and with high affinity to all three 21 bp repeats, and that it required the core sequence AGGC for specific binding. Binding of AP-2 prevented the subsequent binding of members of the CREB/ATF family to an adjacent regulatory motif in the 21 bp repeat. Transfection of an AP-2 expression construct into T-lymphocytes activated gene expression from the HTLV-I LTR. At least two 21 bp repeats were required for high levels of AP-2 activation and mutagenesis of the AP-2 consensus binding sequences in the 21 bp repeats eliminate this activation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628622 TI - A 22 bp cis-acting element is necessary and sufficient for the induction of the yeast KAR2 (BiP) gene by unfolded proteins. AB - The KAR2 gene of Saccharomyces cerevisiae codes for an essential chaperone protein (BiP) that is localized in the lumen of the endoplasmic reticulum (ER). The high basal rate of transcription of KAR2 is increased transiently by heat shock: prolonged induction occurs when unfolded proteins accumulate in the ER. Three cis-acting elements in the KAR2 promoter control expression of KAR2: (i) a GC-rich region that contributes to the high level of constitutive expression, (ii) a functional heat shock element (HSE) and (iii) an element (UPR) that is involved in the induction of BiP mRNA by unfolded proteins. By analyzing internal deletion mutants of the KAR2 promoter, we demonstrate here that these three elements regulate transcription of KAR2 independently. Furthermore, the 22 bp UPR element causes a heterologous (CYC1) promoter to respond to the presence of unfolded proteins in the ER. Extracts of both stressed and unstressed yeast cells contain proteins that bind specifically to synthetic HSE and UPR elements and retard their migration through gels. Binding proteins specific for the UPR element can be fractionated by ammonium sulfate precipitation. Two of the proteins UPRF-1 and UPRF-2 (which is apparently a proteolytic degradation product of UPRF-1) bind inefficiently to mutant versions of the UPR that are unable to confer responsiveness to unfolded proteins to the (CYC1) promoter. UPRF-1 therefore displays the properties expected of a transcription factor that is involved in the sustained response of the KAR2 promoter to unfolded proteins in the ER. These experiments show that yeast cells can activate a transcription factor that stimulates expression of a nuclear gene in response to the accumulation of unfolded proteins in another cellular compartment. PMID- 1628623 TI - Activation of mammalian DNA methyltransferase by cleavage of a Zn binding regulatory domain. AB - Mammalian DNA (cytosine-5) methyltransferase contains a C-terminal domain that is closely related to bacterial cytosine-5 restriction methyltransferase. This methyltransferase domain is linked to a large N-terminal domain. It is shown here that the N-terminal domain contains a Zn binding site and that the N- and C terminal domains can be separated by cleavage with trypsin or Staphylococcus aureus protease V8; the protease V8 cleavage site was determined by Edman degradation to lie 10 residues C-terminal of the run of alternating lysyl and glycyl residues which joins the two domains and six residues N-terminal of the first sequence motif conserved between the mammalian and bacterial cytosine methyltransferases. While the intact enzyme had little activity on unmethylated DNA substrates, cleavage between the domains caused a large stimulation of the initial velocity of methylation of unmethylated DNA without substantial change in the rate of methylation of hemimethylated DNA. These findings indicate that the N terminal domain of DNA methyltransferase ensures the clonal propagation of methylation patterns through inhibition of the de novo activity of the C-terminal domain. Mammalian DNA methyltransferase is likely to have arisen via fusion of a prokaryotic-like restriction methyltransferase and an unrelated DNA binding protein. Stimulation of the de novo activity of DNA methyltransferase by proteolytic cleavage in vivo may contribute to the process of ectopic methylation observed in the DNA of aging animals, tumors and in lines of cultured cells. PMID- 1628624 TI - E.coli polynucleotide phosphorylase expression is autoregulated through an RNase III-dependent mechanism. AB - It has been previously shown that the pnp messenger RNAs are cleaved by RNase III at the 5' end and that these cleavages induce a rapid decay of these messengers. A translational fusion between pnp and lacZ was introduced into the chromosome of a delta lac strain to study the expression of pnp. In the presence of increased cellular concentrations of polynucleotide phosphorylase, the level of the hybrid beta-galactosidase is repressed, whereas the synthesis rate of the corresponding message is not significantly affected. In the absence of pnp, the level of the hybrid protein increases strongly. Thus, polynucleotide phosphorylase is post transcriptionally autocontrolled. However, autocontrol is totally abolished in strains where the RNase III site on the pnp message has been deleted or in strains devoid of RNase III. These results suggest that polynucleotide phosphorylase requires RNase III cleavages to autoregulate the translation of its message. Other mutations in the ribosome binding site region support the hypothesis that this 3' to 5' processive enzyme could recognize a specific repressor binding site at the 5' end of pnp mRNA. Implications of these results on the mechanism of regulation and on messenger degradation are discussed. PMID- 1628626 TI - Co-amplified markers alternate in megabase long chromosomal inverted repeats and cluster independently in interphase nuclei at early steps of mammalian gene amplification. AB - Two-colour in situ hybridization with probes for two co-amplified markers located several megabases apart on chromosome 1 has been used to analyse early stages of adenylate deaminase 2 (AMPD2) gene amplification in Chinese hamster cells. In the amplified chromosomal structures, the distribution of hybridization spots identifies megabase-long inverted repeats. Their organization is remarkably well accounted for if breakage-fusion-bridge cycles involving sister chromatids drive the amplification process at these early stages. During interphase the markers often segregate into distinct nuclear domains. Many nuclei have bulges or release micronuclei, carrying several copies of one or both markers. These observations indicate that the amplified units destabilize the nuclear organization and eventually lead to DNA breakage during interphase. We propose a model in which interphase breakage has a role in the progression of gene amplification. PMID- 1628625 TI - Primary structure and binding activity of the hnRNP U protein: binding RNA through RGG box. AB - Heterogeneous nuclear ribonucleoproteins (hnRNPs) are thought to influence the structure of hnRNA and participate in the processing of hnRNA to mRNA. The hnRNP U protein is an abundant nucleoplasmic phosphoprotein that is the largest of the major hnRNP proteins (120 kDa by SDS-PAGE). HnRNP U binds pre-mRNA in vivo and binds both RNA and ssDNA in vitro. Here we describe the cloning and sequencing of a cDNA encoding the hnRNP U protein, the determination of its amino acid sequence and the delineation of a region in this protein that confers RNA binding. The predicted amino acid sequence of hnRNP U contains 806 amino acids (88,939 Daltons), and shows no extensive homology to any known proteins. The N-terminus is rich in acidic residues and the C-terminus is glycine-rich. In addition, a glutamine-rich stretch, a putative NTP binding site and a putative nuclear localization signal are present. It could not be defined from the sequence what segment of the protein confers its RNA binding activity. We identified an RNA binding activity within the C-terminal glycine-rich 112 amino acids. This region, designated U protein glycine-rich RNA binding region (U-gly), can by itself bind RNA. Furthermore, fusion of U-gly to a heterologous bacterial protein (maltose binding protein) converts this fusion protein into an RNA binding protein. A 26 amino acid peptide within U-gly is necessary for the RNA binding activity of the U protein. Interestingly, this peptide contains a cluster of RGG repeats with characteristic spacing and this motif is found also in several other RNA binding proteins. We have termed this region the RGG box and propose that it is an RNA binding motif and a predictor of RNA binding activity. PMID- 1628627 TI - Unusual stability of recombination intermediates made by Escherichia coli RecA protein. AB - The structure and stability of recombination intermediates made by RecA protein have been investigated following deproteinization. The intermediates consist of two duplex DNA molecules connected by a junction, as visualized by electron microscopy. Although we expected the structures to be highly unstable due to branch migration of the junction, this was not the case. Instead, we found that the intermediates were stable at 37 degrees C. At 56 degrees C, greater than 60% of the intermediates remained after 6 h of incubation. Only at higher temperatures was significant branch migration observed. This unexpected stability suggests that the formation of extensive lengths of heteroduplex DNA in Escherichia coli is likely to require the continued action of proteins, and does not occur via spontaneous branch migration. We show that heteroduplex DNA may be formed in vitro by ATP-dependent strand exchange catalysed by RecA protein or by the RuvA and RuvB proteins of E. coli. PMID- 1628628 TI - Sequence-specific interaction of the Salmonella Hin recombinase in both major and minor grooves of DNA. AB - The Hin recombinase of Salmonella catalyzes a site-specific recombination event which leads to flagellar phase variation. Starting with a fully symmetrical recombination site, hixC, a set of 40 recombination sites which vary by pairs of single base substitutions was constructed. This set was incorporated into the Salmonella-specific bacteriophage P22 based challenge phage selection and used to define the DNA sequence determinants for the binding of Hin to DNA in vivo. The critical sequence-specific contacts between a Hin monomer and a 13 bp hix half site are at two T:A base pairs in the major groove of the DNA which are separated by one base pair, and two consecutive A:T contacts in the minor groove. The base substitutions in the major groove recognition portion which were defective in binding Hin still retained residual binding capability in vivo, while the base pair substitutions affecting the minor groove recognition region lost all in vivo binding. Using in vitro binding assays, Hin was found to bind to hix symmetrical sites with A:T base pairs or I:C base pairs in the minor groove recognition sequences, but not to G:C base pairs. In separate in vitro binding assays, Hin was equally defective in binding to either a G:C or a I:C contact in a major groove recognition sequence. Results from in vitro binding assays to hix sites in which 3-deazaadenine was substituted for adenine are consistent with Hin making a specific contact to either the N3 of adenine or O2 of thymine in the minor groove within the hix recombination site on each symmetric half-site. These results taken with the results of previous studies on the DNA binding domain of Hin suggest a sequence-specific minor groove DNA binding motif. PMID- 1628629 TI - An endonuclease with multiple cutting sites, Endo.SceI, initiates genetic recombination at its cutting site in yeast mitochondria. AB - Endo.SceI is a mitochondrial sequence-specific endonuclease which has multiple cutting sites. In order to examine the possible role of Endo.SceI in homologous recombination, we analyzed the mode of recombination upon mating using antibiotic resistance markers on the mitochondrial genome. The segregation of a marker located very close to one of the Endo.SceI cutting sites showed a disparity (polarized segregation, i.e. gene conversion). This gene conversion depended on the presence of the functional Endo.SceI gene. In vivo cutting of mitochondrial DNA upon mating was detected at the cutting site in the antibiotic marker region, which also depended on the Endo.SceI activity. These results suggest that mitochondrial recombination is induced by cleavage of mitochondrial DNA by this sequence-specific endonuclease. This is the first demonstration that a sequence specific endonuclease with multiple cutting sites induces genetic recombination. PMID- 1628632 TI - Controlled infusion devices: applications in anaesthetic practice. PMID- 1628631 TI - A novel regulatory myosin light chain gene distinguishes pre-B cell subsets and is IL-7 inducible. AB - We describe a novel regulatory myosin light chain gene (termed precursor lymphocyte-specific regulatory light chain or PLRLC) that is expressed specifically in precursor B and T lymphocytes. PLRLC is the first example of a regulatory myosin light chain gene which displays specific expression in non muscle cells. PLRLC is expressed in adult bone marrow derived normal and transformed pre-B cells; in the former, PLRLC expression levels are induced by the pre-B cell specific growth factor interleukin-7 (IL-7). PLRLC is not expressed in either transformed pre-B cells derived from fetal liver or in normal fetal liver pre-B clones grown in the presence of IL-7. Therefore this gene provides the first marker that clearly distinguishes these two pre-B subsets. Finally, several of the different PLRLC transcripts potentially encode regulatory myosin light chains with unique structural features. The unique distribution, regulation and structural features of the PLRLC gene products suggest an important role for PLRLC during lymphocyte development. PMID- 1628630 TI - Surface IgM mediated regulation of RAG gene expression in E mu-N-myc B cell lines. AB - Transgenic mice carrying either the c-myc or N-myc oncogene deregulated by the immunoglobulin heavy chain enhancer element (E mu) develop both pre-B and B cell lymphomas (E mu-c-myc and E mu-N-myc lymphomas). We report here that B cell lines derived from these tumors, as well as a line derived from v-myc retroviral transformation, simultaneously express surface immunoglobulin (a hallmark of mature B cells) as well as a common subset of genes normally restricted to the pre-B stage of development-including the recombinase activating genes RAG-1 and RAG-2. Continued RAG-1 and RAG-2 expression in these lines is associated with VDJ recombinase activity detected with a VDJ recombination substrate. Cross-linking of the surface immunoglobulin on these lines with an anti-mu antibody leads to rapid, specific and reversible down-regulation of RAG-1 and RAG-2 gene expression. We also find that a small but significant percentage of normal surface immunoglobulin bearing bone marrow B cells express the RAG-1 gene. These findings are discussed in the context of their possible implications for the control of specific gene expression during the pre-B to B cell transition. PMID- 1628633 TI - Spinal monitoring during vertebral column surgery under continuous alfentanil infusion. AB - An anaesthetic technique for surgical procedures on the vertebral column is described consisting of a continuous infusion of a short acting opioid, alfentanil, and a muscle relaxant, vecuronium, in combination with positive pressure ventilation using a nitrous oxide/oxygen mixture. It is shown that the two standard forms of spinal monitoring, wake-up testing and somatosensory cortical evoked potentials, can be employed effectively using this anaesthetic technique. Wake-up testing was performed in 23 patients. Average wake-up time was 10 min (SD 3.7 min). Evoked responses suitable for spinal monitoring could be obtained in 60 of 61 patients. PMID- 1628634 TI - Anaesthetic interaction between thiopentone and ketamine. AB - The anaesthetic effect of thiopentone, ketamine and their combinations were studied in 150 patients of ASA Grades I and II. The ability to open eyes on command and purposeful motor response to noxious pressure on the trapezius muscle were used as endpoints of anaesthesia. Dose-response curves for thiopentone, ketamine and their combinations were determined with a probit procedure and compared with isobolographic analysis. The interaction between thiopentone and ketamine was found to be additive for both endpoints of anaesthesia. PMID- 1628635 TI - Halothane 2% for caesarean section. AB - During the induction-delivery interval for Caesarean section delivery, 2% halothane in pure oxygen was administered. The technique was compared to a 0.5% halothane in 50% oxygen/50% nitrous oxide anaesthesia. When a continuous infusion of oxytocin was administered, no excessive haemorrhage was seen. No maternal reminiscence was seen using 2% halothane, but awareness was recorded using 0.5% halothane in 50% nitrous oxide in 15% of the mothers. When there were no signs of preoperative fetal distress, the neonates were unaffected by the halothane concentration provided the induction-delivery interval was short. In cases of fetal distress, the administration of 2% halothane further aggravated the condition of the neonates, as indicated by lowered 1-min Apgar scores, umbilical oxygen tensions, pH and base excess values. PMID- 1628636 TI - Partial attenuation of the pressor response to endotracheal intubation. A comparison of the effects of intravenous clonidine and fentanyl. AB - In a randomized, double-blind placebo controlled study, intravenous clonidine, fentanyl and saline were compared for both their effect on the cardiovascular response to intubation, and early post-operative pain. The patients treated with fentanyl and clonidine were more sedated and the requirements for induction agents were lower compared to the control group. On intubation, both the active treatments resulted in a smaller increase in both heart rate and mean arterial pressure compared to the control group. There was no significant difference in recovery times in the three groups. Although the time to first request for analgesia was longer in the clonidine group compared to both the fentanyl and saline groups, the difference in morphine requirements between the groups was not significant. The differences between the two active treatments were not significant, and clonidine offered no additional benefits over fentanyl for this purpose. PMID- 1628637 TI - Dreaming and anaesthesia: total i.v. anaesthesia with propofol versus balanced volatile anaesthesia with enflurane. AB - Sixty consecutive ASA Grades I and II patients scheduled for elective ear, nose and throat surgery were randomly assigned to receive either total i.v. anaesthesia with propofol ('propofol group') or 'balanced technique' with thiopentone induction followed by N2O and enflurane. Patients were asked whether they had experienced dreams immediately after extubation when verbal communication was established, in the recovery room and in the ward on the evening of the day of surgery. Thirteen patients in the propofol group (43%) and three patients in the enflurane group (10%) reported dreaming (P less than 0.05) when asked as soon as verbal communication was established. In the recovery room and in the ward only three patients of the propofol group (10%) and one patient in the enflurane group (3%) remembered that they had been dreaming (NS). To avoid underestimating the frequency of peri-operative dreaming, post-operative interviews should take place as soon as possible after conversing is possible. PMID- 1628638 TI - A simple system for patient-controlled analgesia. AB - A simple system for patient-controlled analgesia made from disposable items and using hydrostatic pressure for its driving force is described. The system has been used in 200 patients undergoing intra-abdominal gynaecological surgery who were supervised in a general ward. Morphine was used as the analgesic in 150 patients and pethidine in 50. In the morphine group, analgesia was inadequate in eight and use was discontinued in a further 20 patients for various reasons. In the remaining 122, the system worked well and the majority of patients obtained satisfactory analgesia. Details of analgesic administration and requirements, pain and sedation assessments, and patient appreciation in 50 patients are given. In the group receiving pethidine, analgesia was unsatisfactory in two and use was discontinued in eight. The 24-h consumption of pethidine in 20 patients is recorded together with FVC and FEV1 changes and linear analogue scores for pain. It is suggested that the system provides a means of making the benefits of patient-controlled analgesia more widely available. PMID- 1628639 TI - Effects of intrathecal and intraperitoneal morphine on gastrointestinal motility in the rat. AB - A method has been developed to compare gastrointestinal (GI) transit time after intrathecal (i.t.) drug injection in the rat. Each animal had a catheter implanted in the i.t. space. Eight rats, on three separate occasions, had either i.t. morphine 16 micrograms kg-1 (in 50 microliters) or intraperitoneal (i.p.) morphine (0.1%) 7.5 mg kg-1 or i.t. saline (50 microliters). The dose of morphine was the ED50 for analgesia by each route. After halothane and oxygen anaesthesia, 10 steel balls and 1 ml of contrast medium were placed into the stomach, the whole procedure being completed within 5 min. Radiographs were taken at 5 min, 3, 6 and 24 h, and the number of balls in the stomach, small and large intestine were counted. The inhibitory effect of i.t. or i.p. morphine on gut motility caused an equally significant delay at 6 h. In a separate series of eight rats the delay by i.t. morphine could be completely antagonized by i.p. naloxone 1 mg kg-1. Thus, i.t. morphine in an analgesic dose even though smaller than the i.p. dose has a similar inhibitory effect on GI tract motility in the rat. This method would enable comparisons on GI transit to be made between a variety of intrathecally administered drugs. PMID- 1628640 TI - Role of paf-acether in protamine-induced thrombocytopenia in rabbits. AB - The effects of protamine (6 mg kg-1) injected after heparin (5 mg kg-1) have been studied in five groups of five New Zealand white rabbits. Group I was treated with the sequence heparin-protamine and group II with protamine alone. The animals of groups III and IV received respectively intravenous indomethacin (3 mg kg-1) and BN 52021 (3 mg kg-1), a paf receptor antagonist before the sequence heparin-protamine. Group V was pre-treated with indomethacin and BN 52021 before heparin reversal with protamine. In group I, immediate thrombocytopenia (44.1 +/- 4.6% of baseline level, P less than 0.05) and leucopenia (55.5 +/- 2.3% of baseline level, P less than 0.05) were observed 30 s after protamine reversal of heparin, paralleled with an increase in blood paf levels (27.6 +/- 27.6 vs. 148.2 +/- 48.9 pg ml-1, P less than 0.05). In group II, protamine alone induced no change in platelet count nor in blood paf levels (55 +/- 10 vs. 52.5 +/- 20 pg ml 1, P greater than 0.05). Pre-treatment with indomethacin alone (group III) did not protect the animals against the haematological changes induced by the heparin protamine complexes. Pre-treatment with the paf receptor antagonist, alone or in association with indomethacin, delayed the occurrence of thrombocytopenia 3 min after protamine administration but the leucopenia was the same as in group I. This study demonstrated that paf is implicated in the immediate thrombocytopenia occurring after protamine reversal of heparin in rabbit. PMID- 1628641 TI - The polyanion-binding domain of cytoplasmic Lys-tRNA synthetase from Saccharomyces cerevisiae is not essential for cell viability. AB - Cytoplasmic Lys-tRNA synthetase (LysRS) from Saccharomyces cerevisiae is a dimeric enzyme made up of identical subunits of 68 kDa. By limited proteolysis, this enzyme can be converted to a truncated dimer without loss of activity. Whereas the native enzyme strongly interacts with polyanionic carriers, the modified form displays reduced binding properties. KRS1 is the structural gene for yeast cytoplasmic LysRS. It encodes a polypeptide with an amino-terminal extension composed of about 60-70 amino acid residues, compared to its prokaryotic counterpart. This segment, containing 13 lysine residues, is removed upon proteolytic treatment of the native enzyme. The aim of the present study was to probe in vivo the significance of this amino-terminal extension. We have constructed derivatives of the KRS1 gene, encoding enzymes lacking 58 or 69 amino terminal residues and, by site-directed mutagenesis, we have changed four or eight lysine residues from the amino-terminal segment of LysRS into glutamic acids. Engineered proteins were expressed in vivo after replacement of the wild type KRS1 allele. The mutant enzymes displayed reduced specific activities (2-100 fold). A series of carboxy-terminal deletions, encompassing 3, 10 or 15 amino acids, were introduced into the LysRS mutants with modified amino-terminal extensions. The removal of three residues led to a 2-7-fold increase in the specific activity of the mutant enzymes. This partial compensatory effect suggests that interactions between the two extreme regions of yeast LysRS are required for a proper conformation of the native enzyme. All KRS1 derivatives were able to sustain growth of yeast cells, although the mutant cell lines displaying a low LysRS activity grew more slowly. The expression, as single-copy genes, of mutant enzymes with a complete deletion of the amino-terminal extension or with four Lys----Glu mutations, that displayed specific activities close to that of the wild-type LysRS, had no discernable effect on cell growth. We conclude that the polycationic extensions of eukaryotic aminoacyl-tRNA synthetases are dispensable, in vivo, for aminoacylation activities. The results are discussed in relation to the triggering role in in situ compartmentalization of protein synthesis that has been ascribed to the polypeptide-chain extensions that characterize most, if not all, eukaryotic aminoacyl-tRNA synthetases. PMID- 1628642 TI - Optimization of yeast-expressed human liver cytochrome P450 3A4 catalytic activities by coexpressing NADPH-cytochrome P450 reductase and cytochrome b5. AB - Human liver P450 NF25 (CYP3A4) had been previously expressed in Saccharomyces cerevisiae using the inducible GAL10-CYC1 promoter and the phosphoglycerate kinase gene terminator [Renaud, J. P., Cullin, C., Pompon, D., Beaune, P. and Mansuy, D. (1990) Eur. J. Biochem. 194, 889-896]. The use of an improved expression vector [Urban, P., Cullin, C. and Pompon, D. (1990) Biochimie 72, 463 472] increased the amounts of P450 NF25 produced/culture medium by a factor of five, yielding up to 10 nmol/l. The availability of recently developed host cells that simultaneously overexpress yeast NADPH-P450 reductase and/or express human liver cytochrome b5, obtained through stable integration of the corresponding coding sequences into the yeast genome, led to biotechnological systems with much higher activities of yeast-expressed P450 NF25 and with much better ability to form P450 NF25-iron-metabolite complexes. 9-fold, 8-fold, and 30-fold rate increases were found respectively for nifedipine 1,4-oxidation, lidocaine N deethylation and testosterone 6 beta-hydroxylation between P450 NF25-containing yeast microsomes from the basic strain and from the strain that both overexpresses yeast NADPH-P450 reductase and expresses human cytochrome b5. Even higher turnovers (15-fold, 20-fold and 50-fold rate increases) were obtained using P450 NF25-containing microsomes from the yeast just overexpressing yeast NADPH-P450 reductase in the presence of externally added, purified rabbit liver cytochrome b5. This is explained by the fact that the latter strain contained the highest level of NADPH-P450 reductase activity. It is noteworthy that for the three tested substrates, the presence of human or rabbit cytochrome b5 always showed a stimulating effect on the catalytic activities and this effect was saturable. Indeed, addition of rabbit cytochrome b5 to microsomes from a strain expressing human cytochrome b5 did not further enhance the catalytic rates. The yeast expression system was also used to study the formation of a P450-NF25-iron metabolite complex. A P450 Fe(II)-(RNO) complex was obtained upon oxidation of N hydroxyamphetamine, catalyzed by P450-NF25-containing yeast microsomes. In microsomes from the basic strain expressing P450 NF25, 10% of the starting P450 NF25 was transformed into this metabolite complex, whereas more than 80% of the starting P450 NF25 led to complex formation in microsomes from the strain overexpressing yeast NADPH-P450 reductase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628643 TI - Malonate decarboxylase of Malonomonas rubra, a novel type of biotin-containing acetyl enzyme. AB - Cell suspensions or crude extracts of Malonomonas rubra grown anaerobically on malonate catalyze the decarboxylation of this substrate at a rate of 1.7-2.5 mumol.min-1.mg protein-1 which is consistent with the malonate degradation rate during growth. After fractionation of the cell extract by ultracentrifugation, neither the soluble nor the particulate fraction alone catalyzed the decarboxylation of malonate, but on recombination of the two fractions 87% of the activity of the unfractionated extract was restored. The decarboxylation pathway did not involve the intermediate formation of malonyl-CoA, but decarboxylation proceeded directly with free malonate. The catalytic activity of the enzyme was completely abolished on incubation with hydroxylamine or NaSCN. Approximately 50 65% of the original decarboxylase activity was restored by incubation of the extract with ATP in the presence of acetate, and the extent of reactivation increased after incubation with dithioerythritol. Reactivation of the enzyme was also obtained by chemical acetylation with acetic anhydride. These results indicate modification of the decarboxylase by deacetylation leading to inactivation and by acetylation of the inactivated enzyme specimens leading to reactivation. It is suggested that the catalytic mechanism involves exchange of the enzyme-bound acetyl residues by malonyl residues and subsequent decarboxylation releasing CO2 and regenerating the acetyl-enzyme. The decarboxylase was inhibited by avidin but not by an avidin-biotin complex indicating that biotin is involved in catalysis. A single biotin-containing 120 kDa polypeptide was present in the extract and is a likely component of malonate decarboxylase. PMID- 1628644 TI - Fluorescence study of the macrolide pentaene antibiotic filipin in aqueous solution and in a model system of membranes. AB - The polyene antibiotic filipin (a pentaene) has been studied using photophysical techniques. The polyene self-aggregates in water with a critical micellar concentration of 2 microM. Two approaches were used to evaluate the aggregate dimensions: (a) a lower limit of 10 nm for the aggregate radius was obtained from energy transfer experiments; (b) a formula for rationalizing the turbidity spectrum was derived, and from its application a spherical shape of radius about 50 nm was deduced. The low value for the fluorescence anisotropy of the aggregate (r = 0.02) is compatible with a very loose structure, i.e. the chromophore has very efficient depolarization dynamics that is not controlled by the aggregate size. The Stern-Volmer plot of aggregated filipin fluorescence quenching by iodide is non-linear, presenting a downward curvature. A model was used for the interpretation of these data, along with a study of the quenching in transient state; it was concluded that all the components of the decay are affected by the quencher, i.e. the aggregate has a very open structure with respect to the iodide ion. The partition constants of the polyene, Kp, between a model system of membranes (small unilamellar vesicles of dipalmitoylglycerophosphocholine) and the aqueous phase were determined from anisotropy measurements; the values obtained were Kp (gel phase) = (3.4 +/- 0.8) x 10(3) and Kp (liquid crystal phase) = (7.7 +/- 2.2) x 10(2). The observation that the polyene incorporation is efficient is at variance with the belief that the presence of sterols are essential for the interaction of polyene antibiotics with membranes [for review see Bolard, J. (1986) Biochim. Biophys. Acta 864, 257-304]. PMID- 1628645 TI - Isolation and characterization of a novel type of growth factor derived from serum-free conditioned medium of chicken embryo fibroblasts. AB - A strong mitogenic activity for fibroblastic cells has been found in serum-free medium of growth-arrested primary cultures of chicken embryo fibroblasts (CEF). This serum-free conditioned medium promoted growth of NIH/3T3 cells and primary as well as secondary cultures of CEF. The mitogenic activity was as potent as 5% serum. Half-maximum stimulation was obtained with 20% of the initial concentration of the conditioned medium. The activity eluted at high M(r) (1-2 x 10(5)) from a gel-filtration column under nondenaturing conditions and was trypsin insensitive and thiol insensitive. Treatment with acid or urea converted the mitogen to a low-molecular-mass form, which showed a delayed induction of DNA synthesis. Purification of this factor (10000-fold) to apparent homogeneity was achieved by preparative isoelectric focusing, gel filtration, reverse-phase HPLC and nonreducing SDS/PAGE. The factor, termed CEF-derived growth factor (CDGF) was a 32-kDa, disulfide-linked heterodimer of a 15-kDa and a 17-kDa subunit as judged by SDS/PAGE, with a pI of approximately 7 in 8 M urea. It exhibited partial stability towards heat treatment and was trypsin sensitive. CDGF was active only in its dimeric form and half-maximum stimulation of NIH/3T3 cells was obtained at approximately 10 pM. The mitogenic activity was not suppressible by an antibody neutralizing the activity of transforming growth factor beta 1, 2 and 3 (TGF beta). The physico-chemical properties suggest that CDGF is not identical with one of the common growth factors like fibroblast growth factor, platelet-derived growth factor, epidermal growth factor, insulin-like growth factor, or TGF-beta but rather represents a novel type of growth factor. PMID- 1628646 TI - Futile cycling of glycogen in Fibrobacter succinogenes as shown by in situ 1H-NMR and 13C-NMR investigation. AB - Glycogen was synthesized during all the growth phases in the rumen anaerobic cellulolytic bacterium Fibrobacter succinogenes. Glycogen synthesis and degradation were monitored using in situ 13C and 1H-NMR spectroscopy in resting cells of F. succinogenes. The cells were incubated at 37 degrees C under anaerobic conditions with [1-13C]glucose and [2-13C]glucose. 1H-NMR spectra were used to quantify enrichment by 13C of metabolism products. Glucose was utilized for energy requirements of the bacterium, essentially via the Embden-Meyerhof pathway, leading to the synthesis of succinate and acetate, while glycogen was stored. From [1-13C]glucose, labeling occurred on C2 of succinate and acetate, and on both C1 and C6 of glycogen, the labeling on C1 being predominant. The C6 labeling of glycogen may be explained by scrambling and reversal of the glycolytic pathway at the triose-phosphate and fructose 1,6-bisphosphate level. When the bacteria were incubated first with [1-13C]glucose, then washed and incubated with [2-13C]glucose, the pattern of 13C labeling in the products of the metabolism, as shown by 13C and 1H-NMR spectra, indicated that glycogen was degraded at the same time as it was being stored, suggesting futile cycling of glycogen. The hydrolysis of previously stored glycogen can provide, in the presence of glucose, up to 30% of the carbon source for the bacteria. PMID- 1628647 TI - Distinct forms of human CDC2 identified by novel monoclonal antibodies. AB - Studies on the functional and structural properties of the cdc2 kinase, a key cell-cycle regulator, have been possible thanks to the availability of cdc2 specific immunoreagents. In an attempt to elucidate the biochemical regulation of the cdc2 kinase in more detail, we have raised a series of novel mouse monoclonal antibodies against human recombinant cdc2 protein. The five Mab reported here can be subclassified into two groups according to their interspecies cross-reactivity and distinct immunoprecipitation patterns. Thus, the target epitopes of Mab POH 1, POH-2 and POH-7 (group 1) appear to be limited to a few mammalian species and the fraction of cdc2 immunoprecipitable by these Mab from cellular extracts is considerably enhanced by denaturation. In contrast, the POH-3 and POH-8 (group 2) Mab recognize a denaturation-sensitive epitope on cdc2 which is present in all tested mammalian species. More importantly, each of the two groups of Mab immunoprecipitate forms of cdc2 associated with a characteristic set of cellular proteins, none of which appears to be cyclin A or cyclin B. None of the antibodies precipitated a histone-H1 or casein-kinase activity, although an activity which phosphorylated some of the coprecipitated proteins was coprecipitated with the group 2 Mab. These novel Mab did not interfere with the association of cdc2 with cyclin A in vitro and efficient immunoprecipitation of a panel of cdc2 mutant proteins suggests that the target epitopes may not involve amino acid residues essential for currently known cdc2 functions. The results of the present study provide evidence for the existence of additional forms of the cdc2 protein in exponentially growing human cells, distinct from both the monomeric and the cyclin-bound cdc2 identified so far. PMID- 1628648 TI - Spectral characteristics of cadmium-containing phytochelatin complexes isolated from Schizosaccharomyces pombe. AB - Phytochelatins, heavy-metal-containing peptides with structures (gamma EC)nG, where n = 2-8, have been isolated from higher plants and the fission yeast Schizosaccharomyces pombe. The present work describes the isolation and characterization of several naturally occurring mixed complexes of these peptides from S. pombe exposed to 1 mM CdCl2. A lower-molecular-mass fraction from Sephadex G-50 chromatography yielded three distinct species on further fractionation. HPLC chromatography revealed the presence of peptides with n = 1-4 in varying amounts in these three complexes, referred to as complexes I, II and III. Stoichiometries are proposed for these complexes, based on [Cd], [SH], [S2-] and the amino acid content. Ultraviolet absorption and magnetic circular dichroism spectra of complexes II and III are similar, whereas the CD spectra of these two complexes are strikingly different. Compared to both complexes II and III, the CD bands of complex I are relatively weak. Ultraviolet absorption, CD and magnetic circular dichroism spectra provide a basis for the discussion of structural differences in these complexes. PMID- 1628650 TI - The multimeric structure and disulfide-bonding pattern of bovine kappa-casein. AB - Bovine kappa-casein was analyzed by SDS/PAGE, MS and amino acid sequence analysis in order to determine its multimeric composition and disulfide-bonding pattern. SDS/PAGE revealed that kappa-casein in the native state can range in size from a monomer to a multimeric structure larger than a decamer. Three types of interchain disulfide linkage, Cys11-Cys11, Cys11-Cys88 and Cys88-Cys88, were all assigned in multimers purified from [14C]carboxymethylated and untreated bulk milk, as well as a milk sample from a kappa-casein-variant-B homozygote Co20. These results indicate that multimerization occurs in a random or at present unpredictable disulfide-bonding pattern regardless of the size of the multimer or the genotype. PMID- 1628649 TI - Generation of specific antibodies against the rap1A, rap1B and rap2 small GTP binding proteins. Analysis of rap and ras proteins in membranes from mammalian cells. AB - Specific antibodies against rap1A and rap1B small GTP-binding proteins were generated by immunization of rabbits with peptides derived from the C-terminus of the processed proteins. Immunoblot analysis of membranes from several mammalian cell lines and human thrombocytes with affinity-purified antibodies against rap1A or rap1B demonstrated the presence of multiple immunoreactive proteins in the 22 23 kDa range, although at strongly varying levels. Whereas both proteins were present in substantial amounts in membranes from myelocytic HL-60, K-562 and HEL cells, they were hardly detectable in membranes from lymphoma U-937 and S49.1 cyc cells. Membranes from human thrombocytes and 3T3-Swiss Albino fibroblasts showed strong rap1B immunoreactivity, whereas rap1A protein was present in much lower amounts. In the cytosol of HL-60 cells, only small amounts of rap1A and rap1B proteins were detected, unless the cells were treated with lovastatin, an inhibitor of hydroxymethylglutaryl-coenzyme A reductase, suggesting that both proteins are isoprenylated. By comparison with recombinant proteins, the ratio of rap1A/ras proteins in membranes from HL-60 cells was estimated to be about 4:1. An antiserum directed against the C-terminus of rap2 reacted strongly with recombinant rap2, but not with membranes from tested mammalian cells. In conclusion, rap1A and rap1B proteins are distributed differentially among membranes from various mammalian cell types and are isoprenylated in HL-60 cells. PMID- 1628651 TI - The kidney as a novel target tissue for protein adduct formation associated with metabolism of halothane and the candidate chlorofluorocarbon replacement 2,2 dichloro-1,1,1-trifluoroethane. AB - Hydrochlorofluorocarbons (HCFCs) have been identified as chemical replacements of the widely used chlorofluorocarbons (CFCs) that are implicated in stratospheric ozone depletion. Many HCFCs are structural analogues of the anesthetic agent halothane and may follow a common pathway of biotransformation and formation of adducts to protein-centered and other cellular nucleophiles. Exposure of rats to a single dose of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) or of the candidate CFC substitute HCFC 123 (2,2-dichloro-1,1,1-trifluoroethane) led to the formation of trifluoroacetylated protein adducts (CF3CO-proteins) not only in the liver, but also in the kidney as a novel target tissue for protein trifluoroacetylation. CF3CO-proteins in the kidney amounted to about 5% of those formed in the liver of the same animal. The amount of CF3CO-proteins formed within the kidney was roughly reflected by the capacity of metabolism of halothane or HCFC 123 by rat kidney microsomes in vitro which amounted to about 10% of that observed with liver microsomes. By immunohistochemistry, CF3CO proteins in the kidney were mainly localized in the tubular segments of the cortex. In the liver, the density of CF3CO-proteins decreased from the central vein towards the portal triad. In vitro incubation of rat liver microsomes with halothane or HCFC 123 resulted in extensive formation of CF3CO-proteins and reproduced faithfully the pattern of liver CF3CO-proteins obtained in vivo. CF3CO proteins generated in vitro were immunochemically not discernible from those generated in vivo. Glutathione (5 mM) and cysteine (5 mM) virtually abolished CF3CO-protein formation; the release of Br- from halothane and Cl- from HCFC 123 was reduced to much lesser a degree. S-Methyl-glutathione, N-acetyl-cysteine, methionine, and N-acetyl-methionine only slightly affected the formation of CF3CO proteins or metabolism of either substrate. The data suggest that metabolism and concomitant CF3CO-protein formation of halothane or of candidate CFC replacements like HCFC 123 is not restricted to the liver but also takes place in the kidney. Furthermore, an in vitro system for CF3CO-protein formation has been developed and used to show that protein-centered and glutathione-centered nucleophilic sites compete for intermediates of metabolism of halothane or of HCFC 123. PMID- 1628652 TI - Molecular cloning, sequencing and restriction mapping of the genomic sequence encoding human proacrosin. AB - In the present study, molecular cloning, sequencing and restriction mapping of the genomic sequence encoding human proacrosin is described. The full-length cDNA encoding human proacrosin was utilized to recover a 17-kb human genomic clone which was sequenced without further subcloning. The nucleotide sequences of the exons agree with the sequence of the cDNA reported previously. More than 500 bases of the promoter region were sequenced and found to be highly GC rich but devoid of an identifiable TATA box. These findings are generally consistent with a recently published report [Keime, S., Adham, I. M. & Engel, W. (1990) Eur. J. Biochem. 190, 195-200]. However, further sequence analysis revealed discrepancies between our clone and that previously reported. Sequencing of the first intron showed similarity with the published data for 54 bases of the 5' region, beginning with the donor splice site, and for 114 bases at the 3' end. However, 500 bases sequenced distal to the initial 54 bases at the 5' end of intron 1 showed no similarity with the published sequence. In addition, the boundaries of intron 3 differed such that a cytosine residue previously reported to be in exon 3 was found to be the first base of exon 4. Detailed studies were undertaken to confirm that our clone constitutes the authentic sequence of human proacrosin. Cloning and characterization of the human proacrosin gene may allow for informative studies of its regulation, and for a more detailed examination of its role in fertilization. PMID- 1628653 TI - Autoactivation of proteinase A initiates activation of yeast vacuolar zymogens. AB - The Saccharomyces cerevisiae PEP4 gene encodes proteinase A, an aspartyl protease. pep4 mutants are defective in the activation of many vacuolar hydrolases, including proteinase B. We have expressed a pep4 mutation which directs the accumulation of pro-proteinase A with a defective active site. Co expression with PEP4 leads to normal processing, i.e. the mutant zymogen is functional as a substrate for the maturation reaction in trans. We conclude that wild-type pro-proteinase A has the ability to mediate its own activation. Elimination of the co-expressed PEP4 gene did not effectively stop the processing of the mutant zymogen, owing to a strong, proteinase-B-dependent, phenotypic lag. In a proteinase-B-negative strain, processing of pro-proteinase A led to an active form of a higher molecular mass than the normal mature form. PMID- 1628654 TI - Characterisation of yeast phosphoglycerate kinase modified by mutagenesis at residue 21. AB - Site-directed mutagenesis has been used to produce mutant forms of yeast phosphoglycerate kinase in which the conserved active-site residue, Arg21, has been replaced by a methionine or a lysine. Kinetic results obtained using these mutant enzymes show that their Km for both 3-phospho-D-glycerate and ATP are significantly different from those recorded for the wild-type enzyme. The Vmax for the lysine mutant is reduced by a factor of two from that of the wild-type enzyme whereas the Vmax for the methionine mutant is reduced more than sevenfold. A very clean electron-density-difference map shows little, if any, evidence of a structural change associated with the C-terminal domain, although resonances in the NMR spectra associated with the ATP-binding site (C-terminal domain) are also affected by the mutation as one might expect from the kinetic results. The NMR data show that binding at both the 3-phospho-D-glycerate and the non-productive ATP-binding site (associated with the N-terminal domain) are affected in the mutant in a way which is different to that associated with the wild-type enzyme. These results, taken together with the X-ray and kinetic data, indicate that the non-productive ATP-binding site and the activating anion-binding site are both associated with the basic patch region of yeast phosphoglycerate kinase. PMID- 1628655 TI - Transcriptional activation of human (2'-5')oligoadenylate synthetase gene expression by the phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate in type-I interferon-treated HL-60 and HeLa cells. AB - (2'-5')Oligoadenylate [(2'-5')(A)n] synthetase is a key enzyme in the interferon elicited antiviral response whose controlled expression in interferon-treated cells has been only partially elucidated. In this investigation, we have compared the modulation of the (2'-5')(A)n synthetase gene by interferon alone and by the combination of interferon and a second cellular effector, 12-O-tetradecanoyl phorbol 13-acetate (TPA). Although TPA alone had no effect on (2'-5')(A)n synthetase, it potentiated the induction of (2'-5')(A)n of synthetase by interferon in HL-60 and HeLa cells by increasing content of its mRNA and an immunoreactive 40-kDa isoenzyme. Since TPA activates protein kinase C (PKC), other PKC-activating phorbol-ester analogues were tested and found to be effective, whereas the PKC inhibitor staurosporine reduced the potentiative activity of TPA. By using the (2'-5')(A)n synthetase gene promoter linked to a reporter gene, chloramphenicol acetyltransferase (CAT), TPA and interferon were found to result in a doubling of CAT activity compared to cells treated with interferon alone. Moreover, when nuclear extracts prepared from control cells or cells treated with TPA and interferon (IFN), separately or together, were incubated with radioactively labeled oligodeoxynucleotides containing the interferon-responsive element (IRE), TPA was shown to down-regulate an IFN inducible IRE/protein complex. These data further suggest that TPA regulates (2' 5')(A)n synthetase gene expression at the level of transcription. PMID- 1628656 TI - CD4 gene transcription is transiently repressed during differentiation of myeloid cells to macrophage-like cells. AB - The CD4 glycoprotein, which serves as receptor for human immunodeficiency virus (HIV), is expressed in several types of cells of hematopoietic origin, including T lymphocytes and monocytes. Triggering differentiation of peripheral blood monocytes, monocytic U-937 or promyelocytic HL-60 precursor cells to macrophage like cells by phorbol ester treatment transiently induced both a rapid reduction in surface CD4, demonstrated by flow-cytometry analysis, and a gradual loss of CD4 mRNA, revealed by Northern-blot analysis. Experiments in HL-60 cells to determine the cause of the observed decay in CD4 mRNA levels suggested that the half-life of CD4 transcripts did not diminish but increased after phorbol ester stimulation. Direct measurement of CD4 gene transcription by run-on analysis indicated that the rate of synthesis of new CD4 mRNA molecules was reduced approximately 10-fold after phorbol ester stimulation, whereas the rate of synthesis of c-fos mRNA resulted in a 2.5-fold increase. These data suggest that phorbol ester treatment specifically reduces CD4 mRNA levels by repressing CD4 gene transcription. These findings may be relevant to understand the regulation of CD4 gene expression during differentiation. PMID- 1628657 TI - Evidence for a sialosyl cation transition-state complex in the reaction of sialidase from influenza virus. AB - The enzyme mechanism of sialidase from influenza virus has been investigated by kinetic isotope methods, NMR, and a molecular dynamics simulation of the enzyme substrate complex. Comparison of the reaction rates obtained with the synthetic substrate 4-methylumbelliferyl-N-acetyl-alpha-D-neuraminic acid and the [3,3-2H] substituted substrate revealed beta-deuterium isotope effects for V/Km ranging over 1.09-1.15 in the pH range 6.0-9.5, whereas the effects observed for V in this pH range increased from 0.979 to 1.07. In D2O, beta DV/Km was slightly increased by 2% and 5% at pD 6.0 and 9.5 respectively, while beta DV was unchanged. Solvent isotope effects of 1.74 were obtained for both beta DV/Km and beta DV at pD 9.5, with beta DV/Km decreasing and beta DV remaining constant at acidic pD. 1H-NMR experiments confirmed that the initial product of the reaction is the alpha-anomer of N-acetyl-D-neuraminic acid. Molecular dynamics studies identified a water molecule in the crystal structure of the sialidase-N-acetyl-D neuraminic acid complex which is hydrogen-bonded to Asp151 and is available to act as a proton donor source in the enzyme reaction. The results of this study lead us to propose a mechanism for the solvent-mediated hydrolysis of substrate by sialidase that requires the formation of an endocyclic sialosyl cation transition-state intermediate. PMID- 1628658 TI - Characterisation of a thermostable alpha-amylase from Bacillus brevis. AB - Biochemical characterization of a novel heat-stable alpha-amylase, produced by a thermophilic strain of Bacillus brevis, has been made. The pattern of the enzyme action on different substrates was studied. It was found that reducing groups were rapidly liberated from amylopectin, soluble and insoluble starch compared to amylose and glycogen. B. brevis alpha-amylase acted via endo-attack producing mainly maltopentaose during the first hour of hydrolysis. The enzyme showed high activity towards maltohexaose and maltoheptaose. The alpha-amylase from B. brevis had a neutral pI and was found to be a glycoprotein, containing 9.2% (by mass) neutral sugars. The enzyme protein possessed a unique high glycine content. Calcium or sodium ions in appropriate concentrations were required for enzyme thermostability. PMID- 1628659 TI - Metabolism of inositol phosphates in the protozoan Paramecium. Characterization of a novel inositol-hexakisphosphate-dephosphorylating enzyme. AB - Basal and stimulated levels of inositol phosphates were determined in the protozoan Paramecium labelled with myo-[3H]inositol. Under resting conditions, intracellular InsP6 (phytic acid), InsP5 and InsP4 concentrations were 140, 10 and 2 microM, respectively. InsP5 was comprised of 56% Ins(1,2,3,4,5)P5 and/or Ins(1,2,3,5,6)P5, 40% Ins(1,2,4,5,6)P5 and/or Ins(2,3,4,5,6)P5 and small amounts of Ins(1,3,4,5,6)P5 and Ins(1,2,3,4,6)P5. InsP4 was mainly Ins(1, 4, 5, 6)P4 and/or Ins(3, 4, 5, 6)P4. Other inositol phosphates were not detected at a detection limit of 50-85 nM. Using various depolarizing and hyperpolarizing stimuli, no significant changes in level of inositol phosphates were observed in vivo, indicating that in the ciliate a contribution of inositol phosphates to signal-transduction mechanisms is unlikely. In homogenates prepared from myo [3H]inositol-labelled cells, a marked relative increase in InsP3 and InsP4 over the concentrations in vivo was observed. These inositol phosphates were identified as degradation products of endogenous InsP6. A novel separation methodology for inositol phosphates was established to allow unequivocal assignment of phosphate locations of all dephosphorylated InsP6-derived products. The dephosphorylation was catalyzed by a phytase-like enzyme with a molecular mass of 240 kDa, most likely of a hexameric structure. The enzyme had a pH optimum of 7.0 and did not require divalent cations for activity. Substrate concentrations above 300 microM were inhibitory. Dephosphorylation of InsP6 by the Paramecium enzyme differs from that of phytases from plants in that it proceeds via a sequential release of phosphate groups from positions 6, 5, 4 and 3 of the myo-inositol ring or/and positions 4, 5, 6 and 1. PMID- 1628660 TI - Inhibition of the acidification of endosomes and lysosomes by the antibiotic concanamycin B in macrophage J774. AB - The antibiotic concanamycin B was found to inhibit oxidized-low-density lipoprotein(LDL)-induced accumulation of lipid droplets in the macrophage J774 at a concentration of 5-10 nM. Concanamycin B inhibited cholesteryl-ester synthesis from [14C]oleate by 50% at 14 nM without affecting the synthesis of triacylglycerol and polar lipids. Degradation of internalized oxidized 125I-LDL was inhibited by about 80% in cells treated with 25 nM concanamycin B, while cell surface binding of oxidized 125I-LDL at 4 degrees C, uptake of surface-bound oxidized 125I-LDL and microsomal acyl-CoA:cholesterol acyltransferase activity were not significantly affected by the antibiotic at 25 nM. When J774 cells were treated with 25 nM concanamycin B at 37 degrees C for 60 min, there was a reduction of about 50% in the activity of cell-surface receptors. This reduction appeared to be due to partial trapping of the receptors within the cells. Concanamycin B significantly inhibited ATP-dependent acidification of endosomes and lysosomes of the J774 cells at a concentration of 4 nM. Since acidic condition of these organelles is required for receptor recycling and hydrolysis of lipoproteins, the results demonstrate that concanamycin-B inhibition of oxidized-LDL-induced accumulation of lipid droplets and cholesteryl esters in macrophages J774 is associated with reduced ATP-dependent acidification of these organelles. PMID- 1628661 TI - Periodic properties of proton conformational shifts in isolated protein helices. An experimental study. AB - In this work, the helix-forming residues in fragments of several proteins (ribonuclease, thermolysin, tendamistat and angiogenin) were identified by NOE and the helix proton shifts were measured as delta changes associated with helix population increments driven by trifluoroethanol addition. When estimated in this way, a regular pattern of helix conformational shifts was clearly seen in the delta delta versus sequence profiles of all the peptides studied. The helix periodicity of the H alpha and H beta resonances was especially clear, an observation that earlier statistical studies of protein delta values failed to predict. Amide protons showed the largest helix shifts, but with a less-sharply defined periodic character. Aromatic residues considerably distorted the periodicity of the helix amide shifts in some peptides, as evidenced by the delta shifts of a RNase A fragment 1-15 analog in which the two aromatic residues were replaced by Ala. The relationship between helix periodicity and peptide amphiphatic character is discussed. PMID- 1628662 TI - The cholesterol-side-chain-cleaving cytochrome P450 spin-state equilibrium. 1. Thermodynamic analysis. AB - We have investigated the spin-state equilibrium of adrenal mitochondrial P450scc (cholesterol-side-chain-cleaving, CYP11A1) by absorption spectroscopy in the Soret band as a function of pH and temperature. The van't Hoff plot of the high spin/low-spin equilibrium is not linear and is shifted towards high spin by lowering the pH. This non-linearity resolves clearly into two phases when the temperature range is extended from 37 degrees C to -20 degrees C using ethylene glycol as anti-freeze cosolvent. This enabled us to measure the enthalpy and entropy changes which are delta HA = 0.7 kJ.mol-1 and delta SA = 5J.K-1.mol-1 at low temperatures and delta HB = -42 kJ.mol-1 and delta SB = -152 J.K-1.mol-1 at high temperatures. The transition temperature, Tbreak, between both phases decreases as a function of pH. The experimental data can be fitted by a minimal reactional model comprising a temperature dependent conformational transition and two ionisation steps (one for each conformation), the pK of which is 1.5 +/- 0.5 higher in the low-temperature conformation. The deduced conformational equilibrium is affected by physiological effectors: Tbreak depends on the nature of the substrate intermediate and on the presence of the physiological electron donor, adrenodoxin. PMID- 1628663 TI - The cholesterol-side-chain-cleaving cytochrome P450 spin-state equilibrium. 2. Conformational analysis. AB - We have confirmed and characterised structurally the enzyme conformational changes deduced from the preceding thermodynamic analysis of the adrenal mitochondrial cholesterol-side-chain-cleaving cytochrome P450 spin-state equilibrium. The spin-transition kinetics following rapid pH jumps were multiphasic in aqueous buffer and biphasic in the presence of 35% ethylene glycol. The activation energy between -2 degrees C and 30 degrees C of both phases was exceptionally high (Ea = 147 kJ.mol-1), suggesting the involvement of large-scale conformational changes. The pH and temperature effects on the CD spectrum show that the enzyme is in equilibrium between at least two conformations which are predicted by the thermodynamic model, but which are not directly correlated to the spin state. The CD changes between 260 nm and 280 nm indicate that the conformation prevailing at high temperatures is characterised by a decreased polarity of the tyrosine environments; the changes between 200 nm and 250 nm suggest furthermore a 4% decreased protein helical content. PMID- 1628664 TI - Purification and characterization of a novel thermostable 4-alpha glucanotransferase of Thermotoga maritima cloned in Escherichia coli. AB - Maltodextrin glycosyltransferase (4-alpha-glucanotransferase) of the extremely thermophilic ancestral bacterium Thermotoga maritima has been purified from an Escherichia coli clone expressing the corresponding T. maritima MSB8 chromosomal gene. T. maritima 4-alpha-glucanotransferase, an approximately 53-kDa monomeric enzyme, is the most thermophilic glycosyltransferase described to date. It retained more than 90% of its maximum activity at temperatures from 55 degrees C up to 80 degrees C. The proposed action modus is the transfer of 1,4-alpha glucanosyl chains, thus resulting in the disproportionation of 1,4-alpha-glucans. It converted soluble starch, amylopectin, and amylose, thereby changing the iodine staining properties of these substrates. The addition of low-molecular mass malto-oligosaccharides, which act as glucanosyl acceptor molecules, enhanced the reaction and resulted in the formation of a series of linear maltohomologues from two to more than nine glucose units in size. Use of either of the malto oligosaccharides maltotetraose, maltopentaose, maltohexaose, or maltoheptaose as sole substrate also yielded linear maltohomologues. On the other hand, maltose and maltotriose were not disproportionated by 4-alpha-glucanotransferase, although both were good acceptors for glucanosyl transfer. Glucose did not function as an acceptor in transfer reactions. Glucose also never appeared as a reaction product. The chain length of glucanosyl segments transferred ranged from two to probably far more than six glucose residues. Comparison of the N-terminal amino acid sequence of 4-alpha-glucanotransferase with other published protein sequences revealed significant similarity to sequences near the N-termini of various eucaryotic maltases and bacterial cyclodextrin glycosyltransferases, suggesting its relatedness on the molecular level with other starch- and maltodextrin-converting enzymes. PMID- 1628665 TI - Site-directed mutagenesis of the Streptomyces R61 DD-peptidase. Catalytic function of the conserved residues around the active site and a comparison with class-A and class-C beta-lactamases. AB - The importance of various residues in the Streptomyces R61 penicillin-sensitive DD-peptidase has been assessed by site-directed mutagenesis. The replacement of the active Ser62 by a Cys residue yielded an inactive protein which was also unable to recognize penicillin. The activity of the Lys65----Arg mutant with the peptide and thiolester substrates was decreased 100-200-fold and the rate of penicillin inactivation was decreased 20,000-fold or more. The mutant thus behaved as a poor, but penicillin-resistant, DD-peptidase. The other studied mutations, the mutations Phe58----Leu, Tyr90----Asn, Thr101----Asn, Phe164--- Ala, Asp225----Glu and Asp225----Asn had little influence on the catalytic and penicillin-binding properties. The Asp225 mutants did not exhibit an increased sensitivity to cefotaxime. The Phe164----Ala mutant was significantly more unstable than the wild-type enzyme. PMID- 1628666 TI - Flow cytometric immunophenotyping: principles and pitfalls. AB - Within the last decade flow cytometry (FCM) has become an integral part of basic immunological research. Elaboration of this technology has been intensively stimulated by a rapidly growing sophistication in monoclonal antibody technology and vice versa. At present numerous applications are established that allow an increasingly detailed insight into the immune system, however, automation still must be considered the "cinderella of the arts". Thus, transition of this powerful approach from a basic to a routine clinical procedure is much more difficult than expected. Sufficient usage of flow cytometers still requires some knowledge of physics and its technical applications. Moreover, several problems arise from the complexity of the biological systems investigated. Here we give a brief introduction to immunofluorescence and FCM followed by a discussion of six exemplary pitfalls that we hope will emphasise the general importance of methodological considerations. PMID- 1628668 TI - Plasma endothelin concentration: relation with vascular resistance and comparison before and after balloon dilatation procedures. AB - Endothelin (ET) is a potent vasoconstrictor peptide with an as yet uncertain physiological role in cardiovascular disease. We measured blood plasma ET concentrations using a recently developed radioimmunoassay and analysed the relations between ET concentration, systemic arterial pressure and systemic vascular resistance. In addition, ET levels before and after percutaneous balloon valvuloplasty and angioplasty were measured. Fifty-one patients were studied: (1) 13 patients with small left-to-right shunting or Kawasaki heart disease (age ranged from 4 to 144 months); (2) 10 patients who had undergone balloon valvuloplasty or angioplasty (age ranged from 1 to 233 months) and (3) 28 healthy infants and children (age ranged from 3 to 152 months). Systemic vascular resistance was calculated by the formula (mean aortic pressure--mean right atrial pressure) X 80/cardiac output (dyne.sec.cm-5). Plasma ET concentrations in healthy children less than 2 years were significantly higher than those over 2 years (2.48 +/- 0.62 vs 1.31 +/- 0.53 pg/ml). In eight patients in groups 1 and 2, plasma ET concentration in the pulmonary artery (2.00 +/- 0.43 pg/ml) was significantly lower than that in the femoral vein (2.39 +/- 0.69 pg/ml) and aorta (2.23 +/- 0.59 pg/ml), suggesting ET secretion derived from endothelial cells in peripheral pulmonary vessels. There was a significant positive correlation between ET concentrations in the femoral vein and systemic vascular resistance (r = 0.55, p less than 0.05). After balloon dilatation ET concentration rose from 2.15 +/- 0.82 pg/ml to 2.61 +/- 1.38 pg/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628669 TI - Diabetes mellitus and exocrine pancreatic insufficiency in a girl with auto immune haemolysis. AB - A 7-year-old girl developed diabetes mellitus and exocrine pancreatic insufficiency after 3.5 years of almost continuous treatment with azathioprine and/or prednisone for idiopathic auto-immune haemolytic anaemia. Although both drugs have been reported to preserve endogenous insulin secretion and to interrupt the diabetogenic process they may be responsible for diabetes and exocrine pancreatic insufficiency in our patient. PMID- 1628670 TI - Hypothalamic failure as a sequela of heterozygous protein C deficiency? AB - Protein C deficiency can lead to cerebrovascular occlusive disease. We describe a patient in whom heterozygous protein C deficiency (type 1) is suspected on the grounds of reduced protein C activity and who suffered from multiple thrombo embolic events involving the brain and peripheral organs. The patient developed hypothalamic failure with hypernatraemia, hypodipsia, hypersomnolence and hyperkapnia, obesity, hyperprolactinaemia, hypogonadotropic hypogonadism and growth hormone deficiency. We hypothesize that protein C deficiency caused cerebrovascular occlusions which eventually led to hypothalamic insufficiency in this patient. Disorders of the anticoagulant system should be looked for in patients with unexplained hypothalamic disease. PMID- 1628667 TI - International classification of osteochondrodysplasias. The International Working Group on Constitutional Diseases of Bone. PMID- 1628671 TI - Association of rib anomalies and malignancy in childhood. AB - A relationship exists between tumours and malformations both generally and in particular combinations. This is also valid for minor errors of morphogenesis suggesting that embryonic tumours are an expression of aberrant intra-uterine morphogenesis. We speculated that these minor aberrations might also manifest in other morphological defects, especially in minor anomalies and malformations of the ribs. We reviewed chest roentgenographs of 1000 children with malignancies for rib anomalies and compared them to 200 patients with mainly infectious diseases. We found 242 rib anomalies in 218 children with tumours (21.8%) and 11 (5.5%) in children without malignancy. This difference was statistically highly significant (P less than 0.001). A high incidence of cervical ribs was found in neuroblastoma (33%), brain tumour (27.4%), leukaemia (26.8%), soft tissue sarcoma (24.5%), Wilms tumour (23.5%) and Ewing sarcoma (17.1%). Only neuroblastoma showed a high incidence of rib bifurcation (4.5%). The increased incidence of these mesenchymal defects in children with malignancies may be another clue for an altered morphogenesis in tumour origin. In neuroblastoma the rib anomaly may be another expression of neurocristopathy as proposed for the association of congenital heart disease and neuroblastoma. PMID- 1628672 TI - Cold haemagglutinin disease complicating Mycoplasma pneumoniae infection in a child under cytotoxic cancer treatment. AB - Acute cold haemagglutinin disease, most commonly associated with underlying mycoplasma infection, is rare in children. A 3-year-old girl who developed this auto-immune disease under intensive cytotoxic treatment for rhabdomyosarcoma is presented. Clinically, a livedo reticularis skin pattern upon exposure to cold which was reversible at room temperature and a spontaneous red cell agglutination of blood samples in vitro led to the diagnosis. Together with bronchopneumonia the girl developed hyper-IgM, high antibody titres against Mycoplasma pneumoniae, as well as high titres of cold agglutinins. Laboratory signs of mild intravascular haemolysis were found. Positive direct antiglobulin test resulted from coating of red cells with C3d and C4. Three different antibodies were identified in serum: nonspecific cold agglutinins without complement activation, anti-I specific cold agglutinins with complement activation, as well as a weak biphasic Donath-Landsteiner haemolysin. Under antibiotic treatment and a short course of predisolone the clinical course was mild. PMID- 1628674 TI - Exomphalos, inguinal hernia, renal agenesis, skeletal dysplasia, heart disease--a "new" syndrome? AB - We report a growth retarded, male child with exomphalos, bilateral direct inguinal hernias, unilateral renal agenesis, congenital heart defect, costovertebral dysplasia, microcephaly, ventricular septal defect, and paroxysmal supraventricular tachycardia associated with Wolff-Parkinson-White syndrome. The natural history of that syndrome is poorly understood and provisional suggestion of a new syndrome will depend on further similar observations. PMID- 1628673 TI - Epidemiology of vertically transmitted HIV-1 infection in Switzerland: results of a nationwide prospective study. Swiss Neonatal HIV Study Group. AB - A nationwide study involving 286 children of human immunodeficiency virus (HIV) infected mothers living in Switzerland has been performed with the participation of all paediatricians interested in HIV infection in the country. Of these children 201 could be followed up prospectively from birth up to a median age of 22 months. Prevalence of HIV infection in Swiss parturients was estimated at 0.1% and apparently remained stable from 1986 to 1989. Vertical transmission rate was estimated at 14%-20%. Variables of maternal or perinatal history were not associated with transmission rate. Transmission to pairs of siblings of the same mothers was discordant in 33% (6 of 18), with always the elder sibling being infected. Postneonatal mortality in infants of HIV-infected mothers followed up from birth was increased 15-fold over the general population with a very high incidence (2 in 100) of sudden infant death apparently unrelated to HIV infection. PMID- 1628675 TI - Nosocomial bacterial infections in very low birth weight infants. AB - The occurrence of congenital and nosocomial bacterial septicaemia has been documented by identifying the number of positive blood cultures by reviewing the laboratory and clinical records of 394 very low birth weight infants who were consecutively admitted to a neonatal intensive care unit over a 40-month period. The incidence of congenital septicaemia was 6% and of nosocomial septicaemia 17%. The commonest causes of congenital infection were Streptococcus agalactiae Staphylococcus epidermidis and Enterococcus faecalis (each in 18% of cases). The commonest cause of nosocomial infection was S. epidermidis (51% of cases), except in infants of birth weight less than 750 g. Risk factors for nosocomial infection were extremely low birth weight, very preterm birth and prolonged ventilation. Nosocomial infection was associated with significantly lengthened hospital admission. PMID- 1628676 TI - Longitudinal assessment of infant lung function following pregnancies complicated by prolonged and preterm rupture of the membranes. AB - Serial measurements of functional residual capacity (FRC) were made in 22 infants (median gestational age at delivery 32 weeks, range 25-40) during the first 2 years of life. All infants had been delivered from pregnancies complicated by prolonged and preterm rupture of the membranes (PPROM) of at least 1 week in duration. The onset of membrane rupture was at a median of 26 weeks (range 15-32) with a median duration of 5.5 weeks (range 1-21). The mean FRC at all postnatal ages studied: 25 ml/kg at 6 and 12 months and 24 ml/kg at 18 and 24 months did not differ significantly from the control population (mean 24 ml/kg). There was, however, a wider scatter of results in the study population: four infants born very preterm consistently had FRC results above the 95% confidence limits of the controls but only two infants had FRCs consistently below this range. These results suggest PPROM may not be an invariable association of abnormal antenatal lung growth. PMID- 1628677 TI - The effects of mid-trimester amniocentesis on lung function in the neonatal period. AB - Lung function tests were carried out on 39 healthy full term babies born after pregnancies subjected to mid-trimester amniocentesis. The results were compared to 42 babies born after normal pregnancies. There were no significant differences in gestational age, birth weight, thoracic gas volume or crying vital capacity. Babies subjected to amniocentesis had a significantly lower dynamic compliance (6.96 ml/cm H2O vs. 8.60 ml/cm H2O) and tended to have higher resistance compared to controls (52.8 cm H2O/l/s vs. 37.3 cm H2O/l/s). This provides further evidence that mid-trimester amniocentesis does have an adverse effect on lung growth and development. PMID- 1628678 TI - Evaluation by colour Doppler and pulsed Doppler sonography of blood flow velocities in intracranial arteries during the early neonatal period. AB - Using a colour pulsed Doppler flow mapping system, we examined the intracranial arteries of 40 healthy infants. The anterior cerebral, basilar, intracranial internal carotid and middle cerebral arteries were visualized clearly enough to evaluate flow velocity at the success rates of 100%, 87.5%, 65% and 82.4%, respectively. In the anterior cerebral, intracranial internal carotid and middle cerebral arteries, the maximum blood flow velocity slightly decreased to a minimum at around 4-6 h after birth, and then gradually increased. The minimum blood flow velocity pattern was similar. The maximum blood flow velocity in the basilar artery decreased from 0-3 h, rapidly increased from 4-6 h, and remained at a steady level thereafter. A possible mechanism for the chronological changes in the intracranial blood flow velocity is discussed. PMID- 1628679 TI - Further evaluation of Vigabatrin therapy in 4-hydroxybutyric aciduria. PMID- 1628680 TI - Severe caffeine intoxication in a preterm neonate. PMID- 1628681 TI - VACTERL plus hydrocephalus: a monogenic lethal condition. PMID- 1628682 TI - Male triplets concordant for X-linked recessive nonsyndromic hypoparathyroidism. PMID- 1628683 TI - Longitudinal study and cost-benefit analysis of the effect of early treatment of posterior cross-bites in the primary dentition. AB - The aim of this study was to follow longitudinally a cohort of preschool children regarding the prevalence of lateral cross-bites and the effect of treatments carried out. Two-hundred-and-twenty-four children were examined when they were 3 5 years old and re-examined at 13-15 years of age. Orthodontic treatment of lateral cross-bites was registered from annual dental records from the Public Dental Service. In the primary dentition, 23.3 per cent of the children showed lateral cross-bites, of whom 5.7 per cent showed a lateral edge-to-edge relation. Selective grinding was carried out in the Public Dental Service in 62 per cent of the cross-bite children. Correction was registered in 64 per cent of these cases. Nine (45 per cent) of the 20 children with untreated lateral deviation showed spontaneous correction. Of the 171 children without cross-bites in the primary dentition, 14 (8 per cent) developed cross-bites in the permanent dentition. Although the benefits of early treatment for the developing dentition are obvious for functional reasons, the effectiveness of grinding, the type of treatment and the timing can be discussed from a cost-benefit point of view. PMID- 1628684 TI - The PAR Index (Peer Assessment Rating): methods to determine outcome of orthodontic treatment in terms of improvement and standards. AB - In orthodontics it is important to objectively assess whether a worthwhile improvement has been achieved in terms of overall alignment and occlusion for an individual patient or the greater proportion of a practitioner's caseload. An objective measure is described that has been validated against the subjective opinions of 74 dentists. Using the weighted PAR Index it was revealed that at least a 30 per cent reduction in PAR score is required for a case to be considered as 'improved' and a change of 22 PAR points to bring about 'great improvement'. For a practitioner to demonstrate high standards the proportion of an individual's case load falling in the 'worse or no different' category should be negligible and the mean reduction should be as high as possible (e.g. greater than 70 per cent). If the mean percentage reduction in PAR score is high and the proportion of cases that have been 'greatly improved' is also high, this indicates that the practitioner is treating a great proportion of cases with a clear need for treatment to a high standard. PMID- 1628685 TI - Changes in mandibular mobility after different procedures of orthognathic surgery. AB - A prospective study including 63 adult Class II and Class III patients was carried out in order to examine short- and long-term effects of four different treatment methods on mandibular mobility. The patients were treated either (Group A, control-group) orthodontically alone or (Group B) by a LeFort I-osteotomy, a (Group C) mandibular advancement or (Group D) a two-jaw surgery/mandibular set back. In the surgery-groups (B, C, and D) maximum opening, protrusion and lateral excursions were measured 2 days pre-operatively (T0), and 3, 8, 14.5, and 25.5 months post-operatively (T1-T4). In the control-group (A) at T0 and T4 was measured, only. Significantly differing effects of the four treatment methods on mandibular mobility were detected. (A) Orthodontic treatment alone, (B) maxillary advancement by LeFort I osteotomy, and (D) two-jaw surgery/mandibular set-back osteotomy did not influence mandibular mobility permanently. Temporary decreases in groups B and D (P less than or equal to 0.05) were observed, however. In contrast, permanent reductions after (C) mandibular advancement took place (P less than or equal to 0.001). Longitudinal survey showed that in all surgery groups recoveries were limited to a short period of 3-14.5 months, depending on the movement. Surprisingly, a closer similarity between the LeFort-I group (B) and the two-jaw surgery group (D), rather than between the sagittal-split groups (C and D), was seen indicating that the problem of reduced mobility after orthognathic surgery can be limited to Class II therapy. It was concluded that in Class III therapy, the application of rigid fixation in combination with a method of maintaining condyle-position, thereby dispensing with maxillomandibular fixation, prevents permanent reductions in mobility and guarantees a rapid recovery to pre-operative mobility levels. PMID- 1628686 TI - Stability of surgical correction of patients with Skeletal III and Skeletal II anterior open bite, with increased maxillary mandibular planes angle. AB - The surgical correction of eleven Class III patients and 10 Class II patients with a long face, increased maxillary mandibular planes angle and anterior open bite was undertaken using bimaxillary surgical procedures. Lateral skull radiographs were examined pre-operatively, 48 hours, and 1 year post-operatively, to quantify the amount and direction of surgical change achieved and the subsequent stability. There was no consistent pattern in the actual movements achieved in either group of patients in the maxillae or the mandibles. Some of the cases being impacted and continuing to impact, others impacting then relapsing. In the Class III patients some of the mandibular set backs remained stable others relapsing and some continuing to move posteriorly. However, despite these inconsistent patterns, there was a 7-degree reduction in the maxillary mandibular planes angle which relapsed by 1.7 degrees over the first year. The overbite was increased from -6 mm to +3.1 mm post-operatively and this relapsed at the 1 year stage to +2.4 mm. The overjet reduced from -4 to 1.7 mm and continued to improve to -0.9 mm at the 1-year stage. In the Class II patients some of the mandibular advancements remained stable others relapsing and some continuing to advance. However, despite these inconsistent patterns there was a 9 degree reduction in the maxillary mandibular planes angle which reduced by a further degree at the 1 year stage. The overbite was increased from -4.6 to -1.6 mm post-operatively and this remained stable at the 1 year stage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628687 TI - Orthodontic and orthopaedic approach in the treatment of skeletal open bite. AB - The aim of this study was to make a detailed evaluation of the changes in the dentofacial structures that could be effective in the elimination of skeletal open bite. The study was performed on 32 skeletal open bite cases which were treated with Begg technique, Edgewise technique, and functional appliances and findings were analysed by multivariate statistical methods. Open bite was significantly reduced in all of the treatment groups. Apart from minor differences, similar changes were observed with Begg and Edgewise technique treatments. During fixed appliance therapy marked increases in the upper and lower posterior dentoalveolar height were observed, and the mandible rotated backwards. On the other hand, with the functional appliances vertical growth of the posterior upper and lower dentoalveolar region was depressed, and the mandible was rotated forwards and upwards with the centre at the premolars. These findings were confirmed by regression analysis: rotational changes in the maxillary and mandibular bases explained 46 per cent of variance of the reduction of open bite in the functional group, while 28 and 16 per cent of variance was explained in the Edgewise and Begg groups, respectively. PMID- 1628688 TI - The treatment of severe 'gummy' Class II division 1 malocclusion using the maxillary intrusion splint. AB - This paper describes a modified Maxillary Intrusion Splint (M.I.S.) system which incorporates a near vertical pull headgear, and its use in the management of severe 'gummy' Class II division 1 malocclusion. The appliance was designed to reduce the visibility and vulnerability of the maxillary incisors in this difficult clinical situation by achieving the intrusion of maxillary teeth, restraining maxillary growth, and encouraging an element of subsequent forward mandibular rotation. The authors' initial experience using this system is presented in a retrospective cephalometric analysis of the lateral skull films of 26 treated patients contrasted with a similar number of comparable controls. The results showed that the principal effects of the M.I.S. were on the maxillary teeth giving decisive overjet control and incisor retraction with actual maxillary incisor intrusion. There was a similar effect on the maxillary molar and the M.I.S. provided effective en masse vertical control of the maxillary dentition. There was some degree of maxillary restraint in the M.I.S. group, but no noticeable difference in the change of mandibular position between the groups at the end of treatment. The possible reasons for this are discussed and suggestions made to improve this aspect of treatment in these patients. PMID- 1628689 TI - Further studies of the pressure from the tongue on the teeth in young adults. AB - The pressures from the tongue on the teeth were recorded simultaneously in four locations lingual to the upper and lower central incisors, and left first molars in 20 young adults with largely normal occlusion. Measurements in the rest position, and during chewing and swallowing were made with an extra-oral pressure transducer incorporated in a fluid-filled system with intra-oral mouthpieces. The size of the dental arches was determined from dental casts. The median pressures in the rest position were low and negative at the upper incisors. Negative pressures at rest were recorded in a few subjects at all four points of measurement, most frequently at the upper incisors and least frequently at the lower molar. The pressures during swallowing were 2-4 times greater than those during chewing. There were no significant correlations between the pressures found and those recorded in the same individuals at an examination 2 years earlier. Positive correlations were found between the pressures recorded in the four locations during the various functions. This was interpreted as being an effect of the size of the tongue. The relatively few correlations between the pressures and the parameters describing the dental arch size indicated an adaptive role of the tongue within the confines of the dental arches. PMID- 1628690 TI - A rationale for the selection of orthodontic wires. AB - A logical basis for the sequence of wires chosen during orthodontic treatment with fixed appliances is presented. This utilizes a new more realistic model for the radial deflection of a segment of the archwire in which the wire is restrained by the ligatures on the misaligned tooth, contacts the inner edges of the brackets either side, and is restrained by the outer ligatures on these brackets. The model, analysed using simple beam theory, allows the determination of the upper and lower bounds for the range of deflection over which orthodontic forces within the optimum range are produced without distortion for any given wire providing its flexural rigidity (EI) and yield stress in bending (sigma o) are known. The same model can be applied to vertical deflections. Some wire sequences recommended on clinical experience appear to conform to this more pragmatic approach, although to cater for even moderate misalignment the forces predicted by the model are higher than normally considered desirable. PMID- 1628692 TI - Immediate and dose-response related increase of biliary excretion of reverse triiodothyronine after propylthiouracil administration. AB - In a group of rats infused with L-thyroxine (0.13 micrograms T4 in 0.6 ml alkaline saline per hour) for 6 h to which an infusion of propylthiouracil (PTU) was added beginning from the 3rd hour (2 mg PTU in 0.6 ml saline per hour) a significant increase of biliary excretion of reverse triiodothyronine (rT3) was found. In another experiment a dose-response related rT3 excretion by bile was observed in groups of rats infused with 0.05, 0.10, 0.20 or 0.40 mg PTU in 1.2 ml alkaline saline per 2 h, all animals receiving a pulse dose of 1 micrograms rT3 at the beginning of PTU infusion. It was concluded that the increase of rT3 excretion results from the inhibition of 5'-deiodinase type I activity in the liver caused by PTU. It thus appears that such phenomenon may be used as in vivo marker of that enzyme activity. PMID- 1628691 TI - Pharmacokinetics of ethinylestradiol and levonorgestrel after administration of two oral contraceptive preparations. AB - Serum concentration profiles and pharmacokinetic parameters (cmax, tmax, AUC24, AUC0-00, MRT) of ethinylestradiol (EE2) and levonorgestrel (LNG) were obtained following administration of two combined oral contraceptives. The constituents of the preparations were as follows: Gravistat (0.05 mg EE2, 0.125 mg LNG); Minisiston (0.03 mg EE2, 0.125 mg LNG). In 20 of the volunteers blood samples were taken before and up to 36 hours following the intake of a single table. In 11 women the investigation was carried out at day 21 of a treatment cycle (steady state condition). In spite of pronounced interindividual variations of the pharmacokinetic data, a clear dependency of EE2 concentration curves on the estrogen dose of the respective preparation could be demonstrated. Under the condition of steady-state (21st day of administration) there was a slight but significant rise of the EE2 peak serum concentrations and a pronounced increase of the LNG levels, closely reflected by elevation of the AUC values. SHBG serum concentration was significantly increased by the 10th day of treatment in all subjects receiving Gravistat, whereas the mean value in the Minisiston-group did not remarkably change. Although LNG is known to be bound to SHBG with high affinity, the missing parallelism between LNG- and SHBG-concentrations suggests other (additional?) mechanisms for the elevated LNG-binding capacity in women taking combined EE2-LNG preparations. PMID- 1628693 TI - Serum thyroglobulin level in patients with diffuse and nodular goiter, after therapeutic application of stable iodine. AB - This study analysed the changes in serum thyroglobulin levels in euthyroid female patients, suffering from diffuse and scintigraphically functional nodular goiter, after therapeutic administration of two preparations of stable iodine: dried bovine thyroid, containing 100 mcg of iodine in one dragee (Thyral, Yugoslav Pharmacopea) and synthetic Na-salt L-thyroxine (Vobenol, with 100 mcg of iodine, too), for relatively short time of following-up, 8 weeks only. Having in mind the key role of TSH in regulation, all aspects of thyroid gland function, the interrelationship between TSH and thyroglobulin concentrations in those patients were also investigated. Prior to the therapy females had elevated thyroglobulin serum concentrations, caused by existence of diffuse and nodular goiter, which reflected an increase in intraglandular turnover of thyroglobulin (192 +/- 140 mcg/L in GROUP A further treated with Thyral and 121 +/- 14.80 +/- mcg/L in GROUP B, whose patients received Vobenol, mean +/- SD). Positive linear correlation between TSH and Tg levels was not established before therapy. Our data indicate that administration of two different preparations containing stable iodine in doses of 100 mcg every second day, during a two months period, resulted in significant decrease in the size of diffuse and nodular goiter, with diminished complains in a great number of patients. In thyroid humoral status, significant decrease of thyroglobulin concentrations was evident in both analysed groups (62 +/- 48 mcg/L, and 60 +/- 66, respectively). Presented results confirmed positive linear correlation between TSH and thyroglobulin in serum samples, after therapy, especially strong in the group treated with dried bovine thyroid. PMID- 1628694 TI - Indirect effects of progesterone on the synthesis and secretion of prolactin in mammotroph-enriched cells. AB - To elucidate the role of steroid hormones in the synthesis and secretion of prolactin (PRL), a mammotroph-enriched cell preparation was made by centrifugal elutriation of trypsin-dispersed anterior pituitary cells from adult male rats. The mammotrophs were enriched by about 2-fold in comparison with those in the initial cell suspension. On the other hand, the ratio of enrichment of gonadotrophs, thyrotrophs and somatotrophs was less than onetenth. The separated mammotrophs were incubated in media containing 17 beta-estradiol and/or progesterone. 17 beta-estradiol increased the levels of PRL in the medium and the cells of 300% and 140%, respectively, and the content of messenger RNA (mRNA) to 193%, whereas progesterone had no such effects. Furthermore, progesterone had no influence on the 17 beta-estradiol-induced increase in the levels of PRL and the contents of PRL mRNA. These results suggest that 17 beta-estradiol regulates PRL synthesis and secretion in mammotrophs, whereas progesterone does not. PMID- 1628695 TI - The effect of serum concentrations and sources on DNA synthesis and insulin secretion of cultured islets. AB - We investigated the effect of different sera, as newborn calf serum, fetal calf serum, rat serum and human serum at various concentrations on biofunctions of cultured pancreatic islets. Islets isolated from newborn LEW. 1 W rats were maintained at 37 degrees C in TCM 199 containing 10 mmol/l glucose and either 1%, 10% or 50% newborn calf serum (NCS), fetal calf serum (FCS), serum obtained from adult syngeneic rats (RS) or different batches of human serum (HS). While exposure of islets to increasing concentrations of NCS significantly inhibited the islet DNA synthesis as well as the glucose stimulated insulin secretion after 2, 4 and 8 days of culture, HS at different concentrations failed to inhibit both, the islet DNA synthesis and the secretory response to glucose at each time point investigated. The action of FCS, RS and 2 further batches of HS on islet DNA synthesis was analysed by short-term culture. The supplementation of the medium with 50% FCS and RS resulted in a marked decrease of H-thymidine incorporation into islet DNA similar to that observed with 50% NCS. In contrast, exposure of islets to different batches of HS never resulted in an inhibition of DNA synthesis. Moreover, the 50% concentration of HS 465 caused a significant stimulation of thymidine incorporation. PMID- 1628696 TI - The dynamics of beta-endorphin release by the hypothalamic nuclei and pituitary gland in sheep under physiological and stress condition. AB - The secretion of beta-endorphin (beta-End) by the infundibular nuclei--median eminence (IN-ME) and paraventricular nuclei (PVN) of the hypothalamus and the anterior lobe (AL) of the pituitary gland was determined in 18 anestrous ewes by RIA assay of this opioid in perfusates collected from these formations. Perfusion with Ringer-Locke solution was carried out on the animals under resting and stress-full conditions, using a pushpull cannula method. Electrical footshocks were used as stress stimuli. Two series of perfusion experiments were performed. In the first, the perfusions were carried out over two hours and perfusates were collected before and during stress for 1 h. In the second series of experiments the dynamics of the release of the opioid by the IN-ME and the pituitary gland were followed by collecting five or six perfusates in 20 min fractions before and during stress, respectively. The first series of experiments showed that the concentrations of beta-End in perfusates from the pituitary gland were much higher than those from the hypothalamic nuclei and that the concentrations of this opioid during stressing rose significantly only in perfusates from the IN-ME nuclei. In the second series of experiments the release of beta-End from the IN ME and pituitary gland was altered by stress. The shift was very characteristic in that the concentrations of the opioid during stimulation initially significantly rose and then gradually declined. The concentration of the opioid in the peripheral blood also rose at the beginning of stimulation and declined as stimulation continued.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628697 TI - Altered monoamine metabolism in the hypothalamus of the genetically obese yellow (Ay/a) mouse. AB - Changes in hypothalamic monoamine metabolism were investigated in the genetically obese yellow (Ay/a) mouse. At the age of 6 weeks when there was no difference in body weight between black (a/a) and yellow (Ay/a) mice, the contents of norepinephrine (NE), dopamine (DA) and their main metabolites (MHPG, DOPAC) were already significantly reduced in yellow (Ay/a) mice. Reduction of 5 hydroxytryptamine (5-HT) level and an increasing 5-HIAA/5-HT ratio has been observed. When a significant increase in body weight in the yellow (Ay/a) mouse at the age of 12 weeks was present, both NE and DA contents have been increased in the hypothalamus of the obese mouse. MHPG level was lower than in the lean mouse, resulting in an increase of MHPG/NE ratio. The present study suggests that the observed reduction in hypothalamic NE and DA metabolism might be involved in the development of overweight gain in the yellow (Ay/a) mouse. PMID- 1628698 TI - A delayed response to acute stimulation with human chorionic gonadotropin in scorbutic rats. AB - Since our previous study revealed low basal testosterone (T) levels and a failure in response to an acute stimulation with human chorionic gonadotropin (HCG) despite of a good response to chronic stimulation in scorbutic mutant rats, time course of the response to HCG was studied and plasma LH level was measured in young adult rats deficient in ascorbic acid for 3 weeks. A single subcutaneous injection of HCG (200 IU) elevated T levels only slightly in plasma and not in testicular tissues of scorbutic rats 1 h after the injection when the levels in ascorbutic rats reached a maximum, while it yielded the same response pattern as in ascorbutic rats after 3 h. A pretreatment with HCG to scorbutic rats for 1 or 4 days resulted in the same response of plasma T as in ascorbutic rats. Plasma LH levels in unstimulated scorbutic rats were about 40% of those in ascorbutic rats. These findings indicate that a prolonged deficiency of ascorbic acid decreases plasma LH, and may reduce the sensitivity of testes to LH. PMID- 1628699 TI - Lack of stimulating effect on thyrotropic and lactotropic secretion during prolonged calcitriol administration. AB - The stimulating effect of calcitriol, administered in the dose of 3 micrograms/day for four days, on the thyrotropic and lactotropic secretion has been proved in earlier studies in healthy humans. The present study was undertaken to confirm or eliminate the stimulatory action of the drug using increasing dosages of 0.75-1.50 micrograms/day for one month. In spite of the fact, that the biologically efficient levels of calcitriol were attained (confirmed indirectly by the rise of urinary calcium excretion, p less than 0.01), the stimulating effect of calcitriol on the basal and TRH induced thyrotropic and lactotropic secretion has not been manifested. In conclusion, the clinical importance of stimulating effect of calcitriol on the thyrotropic and lactotropic secretion is neglected, if only commonly accepted therapeutic dosages up to 1.50 micrograms/day are used. PMID- 1628700 TI - Effect of phospholipase C induced hydrolysis of phospholipids on membrane-bound and water-soluble LH/hCG receptors in porcine corpora lutea. AB - The role of phospholipids in the function of LH/hCG receptors was studied in two receptor preparations: the membrane fraction of porcine corpora lutea (CL) and the water-soluble receptor in follicular fluid (LFF) which was characterized. Digestion of CL membranes with phospholipase C (PL-C) abolished, in a dose responsive manner, specific binding of [125I]hCG and decreased phospholipid concentrations in the membranes. This loss of LH/hCG receptors was prevented by o phenanthroline, an inhibitor of PL-C. A similar effect on membrane-bound receptors was observed when lipids were extracted with ethanol-diethylether. On the other hand, treatment of water-soluble receptors with PL-C or delipidation of LFF with Amberlit IRA 400 had no effect on [125I]hCG specific binding. These data suggest that phospholipids play an important role in the accessibility of membrane-bound receptors but are not involved in direct interaction of gonadotropin with binding sites. PMID- 1628701 TI - Proteins of urea-soluble high molecular weight (HMW) aggregates from diabetic cataract: identification of in vivo glycation sites. PMID- 1628702 TI - Changes. PMID- 1628703 TI - Purification of rat megakaryocyte colony-forming cells using a monoclonal antibody against rat platelet glycoprotein IIb/IIIa. AB - We recently reported the production and characterization of four monoclonal antibodies (MoAbs) against rat platelet glycoprotein IIb/IIIa (GPIIb/IIIa). In this study we developed a simple and efficient three-step procedure, based on positive selection by immunoadsorption (panning) using one MoAb, P55, to purify rat megakaryocyte colony-forming cells (megakaryocyte colony-forming units, CFU MK) from normal bone marrow. Cells obtained after each step were assayed for their ability to form megakaryocyte colonies in the presence of Concanavalin A (Con A)-stimulated rat spleen cell-conditioned medium in soft agar cultures. Marrow cells were first separated on discontinuous Percoll gradients. Cells sedimented at densities between 1.063 and 1.082 g/ml were depleted of cells adherent to plastic tissue culture dishes. The nonadherent cells were further incubated on dishes coated with P55 MoAb. CFU-MK were enriched about 50-fold in the adsorbed cell fraction. This sequential fractionation procedure resulted in a 345-fold (range 276 to 412-fold) enrichment of rat CFU-MK over whole bone marrow cells. The average cloning efficiency of CFU-MK in the final fraction was about 7% (range 5%-9.2%) of the nucleated cells. The overall recovery of CFU-MK averaged 20% (range 9%-29%). The panning step provided a 46-fold enrichment of megakaryocyte burst-forming cells (megakaryocyte burst-forming units, BFU-MK), whose average cloning efficiency in the post-panning fraction was 0.14% (range 0.07%-0.2%). In addition, erythroid burst-forming cells (erythroid burst-forming units, BFU-E) were also significantly enriched by panning, but to a lesser degree than BFU-MK and CFU-MK. By contrast, granulocyte-macrophage colony-forming cells (granulocyte-macrophage colony-forming units, CFU-GM) and erythroid colony forming cells (erythroid colony-forming units, CFU-E) were not enriched by panning. CFU-MK obtained after panning formed megakaryocyte colonies in the presence of recombinant rat interleukin 3 (rIL-3), mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF), or human erythropoietin (hEPO), as has been reported for murine CFU-MK in whole marrow cells. The highly enriched populations of rat CFU-MK should thus provide a basis for the further study of the regulation of megakaryocytopoiesis. PMID- 1628704 TI - In vivo administration of interleukin 6 delays hematopoietic regeneration in sublethally irradiated mice. AB - The in vivo effects of recombinant human interleukin 6 (IL-6) on the hematopoietic system of sublethally (4.8 Gy) x-irradiated mice were investigated. Animals were injected twice daily s.c. with IL-6 (10 micrograms/kg body weight/day) for 7 days following irradiation, and the numbers of hematopoietic stem, progenitor, and circulating blood cells were evaluated at 4, 7, 13, and 23 days. IL-6 caused significant depression of early hematopoiesis (decreased numbers of spleen colony-forming units [CFU-S] and granulocyte-macrophage colony forming cells [GM-CFC]) in the spleens of irradiated mice. Marrow hematopoiesis was less affected by IL-6 injection, although the number of hematopoietic cells was also significantly lower than in irradiated mice injected with carrier alone. The observed decrease in the numbers of hematopoietic cells was not reflected by any significant change in the circulating blood cell numbers, which were similar to those in control irradiated animals. In contrast, IL-6 administered in 100 times higher doses (1000 micrograms/kg/day) caused significant increases in bone marrow and spleen cellularity and GM-CFC numbers, thus accelerating postirradiation hematopoietic regeneration. Our studies show that IL-6, administered in relatively low doses, suppresses postirradiation hematopoietic recovery, decreasing the numbers of stem and progenitor cells in sublethally irradiated mice. PMID- 1628705 TI - Murine interleukin 9 stimulates the proliferation of mouse erythroid progenitor cells and favors the erythroid differentiation of multipotent FDCP-mix cells. AB - Murine interleukin 9 (mIL-9) is a T-cell-derived growth factor that stimulates erythroid burst-forming units (BFU-E) from murine bone marrow. We further investigated this activity using enriched mouse bone marrow progenitors and the multipotent interleukin 3 (IL-3)-dependent FDCP-Mix cell line. We report here that mIL-9 stimulates erythroid burst formation of total bone marrow cells and accessory cell-depleted bone marrow cells, even in serum-free cultures. On the other hand, we observed that although mIL-9 could not support proliferation of FDCP-Mix cells, it favors erythroid differentiation of these cells in the presence of both IL-3 and erythropoietin. These results strongly suggest that mIL 9 acts directly on mouse erythroid progenitor cells. PMID- 1628706 TI - The effect of granulocyte-macrophage colony-stimulating factor on undifferentiated and mature acute myelogenous leukemia blast progenitors. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been used recently to recruit undifferentiated acute myelogenous leukemia (AML) blasts into the S phase of the cell cycle and increase the fraction of cells killed by cell cycle specific drugs. Using three AML blast colony assays combined with a suspension culture (delta assay), we determined the in vitro effect of GM-CSF on mature and undifferentiated AML blast progenitors obtained from bone marrow aspirates of six AML patients. GM-CSF stimulated AML blast colony proliferation at a concentration of 5 ng/ml in the methylcellulose and the agar clonogenic assays in six of six AML marrow samples. However, in the delta assay, which selects for immature AML progenitors, GM-CSF did not affect AML blast colony-forming cells in five of six AML marrow samples at concentrations ranging from 5 to 300 ng/ml. Our data imply that GM-CSF stimulates mature but not undifferentiated AML blast progenitors. It is therefore possible that GM-CSF may not be beneficial as a recruiting agent in most AML patients. PMID- 1628707 TI - Enhancement of hematopoietic recovery in gamma-irradiated mice by the joint use of diclofenac, an inhibitor of prostaglandin production, and glucan, a macrophage activator. AB - The effects of diclofenac (inhibitor of prostaglandin production) and carboxymethylglucan (immunomodulator and an agent stimulating hematopoiesis), when given to mice 1 day before gamma-irradiation, were studied. Both of the agents were administered either alone or in combination. The investigations included the assessment of post-irradiation hematopoietic recovery in terms of bone marrow and spleen cellularity and endogenous spleen colony formation, as well as the determination of the survival of lethally irradiated mice. The results demonstrated at least additive radioprotective effects when mice were given diclofenac and carboxymethylglucan in combination. Experimental evidence provided by the increased 125iodo-deoxyuridine incorporation into the spleen and elevated hydroxyurea kill of endogenous spleen colony-forming units indicated that the beneficial action of the combined treatment could be a consequence of increased cell proliferation in the hematopoietic tissue. It is likely that the inhibition of prostaglandin production (diclofenac action) and the concomitant increased release of growth factors (glucan action) shift the regulatory balance towards the predominance of positive hematopoietic control. PMID- 1628708 TI - Biological activities of tetrapeptide AcSDKP on hemopoietic cell binding to the stromal cell in vitro. AB - The biological activity of the tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) on hemopoietic cell binding to the stromal cells was studied by using a rosette formation technique that quantitatively represents the specific hemopoietic cell binding to the stroma. Marrow hemopoietic cell binding to the stroma was enhanced by AcSDKP. This enhancement was completely neutralized by addition of anti-AcSDKP polyclonal antibody. Furthermore, preincubation of stromal cells with AcSDKP increased hemopoietic cell binding to the stroma, whereas preincubation of hemopoietic cells with AcSDKP showed no increment of the binding. These findings suggest that AcSDKP enhanced hemopoietic cell binding through the activation of stromal cells. PMID- 1628709 TI - The in vitro growth patterns and drug sensitivities of leukemic blast progenitors among the subtypes of acute myelocytic leukemia. AB - The in vitro growth activities and drug sensitivities of leukemic blast progenitors were compared among the subgroups of acute myelocytic leukemia (AML) classified according to the French-American-British (FAB) cooperative group. Leukemic cells separated from the peripheral bloods of AML patients were cultured in methylcellulose media, and the plating efficiencies of primary colonies (PE1) and secondary colonies after replating (PE2) were determined. PE1 and PE2 have been considered to reflect the capacities of terminal divisions and self-renewal of leukemic blast progenitors, respectively. PE1 and PE2 were variable among AML patients; these findings suggest that AML is a heterogeneous disease in terms of the proliferative activities of leukemic cells. No significant correlation was noted between PE1 or PE2 and the AML subtype. The sensitivities to cytosine arabinoside (Ara-C) of leukemic blast progenitors were studied in methylcellulose and suspension cultures. Ara-C sensitivity was not significantly correlated with the AML subtype, either. In contrast, there was statistically significant correlation between PE2 and the remission outcome of the patients, whereas PE1 was not significantly associated with the clinical outcome. The results in the present study indicate that the proliferative activity, especially self-renewal capacity, of leukemic blast progenitors is highly predictive of the prognosis of AML patients but is not significantly correlated with the AML subtype classified by the blast morphology. PMID- 1628710 TI - c-jun and c-fos are expressed by human megakaryocytes. AB - Expression of the main nuclear protooncogenes during terminal megakaryocyte (MK) differentiation is poorly understood. Because previous results have suggested that c-fos and c-jun protooncogenes are expressed in human leukemic cell lines induced to undergo megakaryocytic differentiation, we have analyzed the expression of these two protooncogenes in normal MK. Studies were performed, by in situ hybridization and immunofluorescence, on human MK obtained either directly from bone marrow or from culture of MK progenitors. c-fos and c-jun transcripts were detected in most cultured or fresh marrow MK from adult donors. Expression was much higher in cytologically immature than in mature MK whereas no expression was detected in the most mature MK. c-fos and c-jun expression increased dramatically with MK size. In cultured fetal MK, which all remained small in size, c-fos mRNA was present but at a low level. The c-fos-encoded protein (P62fos) was easily detectable in the great majority of MK. We directly demonstrated that the level of P62fos expression was correlated to MK ploidy by flow cytometry using a three-color staining technique. The involvement of serum and growth factors in the induction of P62fos in MK was studied. Whereas a 3-h serum deprivation resulted in the disappearance of P62fos in MK, several growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3), interleukin 6 (IL-6), interleukin 7 (IL-7), leukemia inhibitory factor (LIF), and transforming growth factor beta (TGF-beta), as well as normal or aplastic serum, were able to reinduce its expression within 2 h. In conclusion, our results suggest that c-jun and c-fos may play a role in the transduction of signals by several growth factors during terminal MK differentiation. PMID- 1628711 TI - Glucose uptake by rat erythroid cells: the effects of erythropoietin and dexamethasone. AB - Erythropoietin (Ep) stimulated glucose uptake by erythroid progenitor cells in the liver of fetal rats, as measured by [3H]2-deoxy-D-glucose uptake. This dose dependent stimulation was maximal at 0.2 U/ml Ep and decreased during cell differentiation. Dexamethasone (DEX) inhibited glucose uptake by erythroid progenitors; this dose-dependent effect was maximal at 10(-7) M DEX. Ep partly counteracted the inhibitory effect of DEX. This antagonism may contribute to the overall antagonism between Ep and glucocorticoids in the development of erythroid tissue in vivo and in vitro. PMID- 1628712 TI - A comparison of the fertility of Dominican, Puerto Rican and mainland Puerto Rican adolescents. AB - Data from three fertility surveys are used to examined the probabilities and determinants of adolescent births among Dominican and Puerto Rican women. Young women in the Dominican Republic are the most likely to have had a child by each year of age from 14 through 24, followed by young women on the Island of Puerto Rico; the probability of an early birth is lowest for Puerto Rican women on the U.S. mainland. Eighteen percent of Dominican women have had a child before their 18th birthday, compared with 13% of women living in Puerto Rico, and 10% of Puerto Rican women in metropolitan New York. The cumulative probabilities that Puerto Rican women will have borne a child before their 20th birthday are almost identical, whether the women live on the island or the U.S. mainland, but the difference between Puerto Rican and Dominican women widens. The order is reversed, however, in the analysis of premarital births: The probability of a premarital birth during adolescence is highest for Puerto Rican women in New York, and lowest for Dominican women. In a separate logistic regression analysis, education and age at first sexual intercourse are shown to be important determinants of adolescent fertility in all three populations. PMID- 1628713 TI - Current oral contraceptive use instructions: an analysis of patient package inserts. AB - Oral contraceptive use instructions contained in manufacturers' patient package inserts (PPIs) are often inconsistent or conflicting, both among manufacturers and among different brands and regimens from the same manufacturer. Instructions on what to do about missed pills are often incomplete or inadequate, as are instructions on backup contraceptive use when pills are missed. The format of many PPIs is confusing and makes instructions difficult to find and read. Comprehending the PPIs requires the user to read at a 10th-12th-grade level, far higher than the generally accepted 5th-6th grade level considered standard for health education materials. PMID- 1628714 TI - High-risk sexual behavior among heterosexual undergraduates at a midwestern university. AB - Approximately 80% of a self-selected sample of 593 heterosexual undergraduate college students studied at a large Midwestern state university in 1988 had ever experienced penile-vaginal or penile-anal intercourse. One-fifth of the 477 sexually experienced women and men said they had had heterosexual and intercourse. The mean age at first vaginal intercourse was 17, while the mean age at first anal intercourse was about 18.5. Although less than four years, on average, had elapsed since the respondents' first vaginal or anal intercourse, females reported having had an average of 5.6 sexual partners, and males reported an average of 11.2 partners. PMID- 1628715 TI - Family planning, sexually transmitted diseases and contraceptive choice: a literature update--Part II. PMID- 1628717 TI - Widespread screening seeks to lower Chlamydia prevalence. PMID- 1628716 TI - Medically indigent women seeking abortion prior to legalization: New York City, 1969-1970. AB - If the efforts now underway to limit access to abortion services in the United States are successful, their greatest impact will be on women who lack the funds to obtain abortions elsewhere. There is little published information, however, about the experience of medically indigent women who sought abortions under the old, restrictive state laws. This article details the psychiatric evaluation of 199 women requesting a therapeutic abortion at a large municipal hospital in New York City under a restrictive abortion law. Thirty-nine percent had tried to abort the pregnancy. Fifty-seven percent had concrete evidence of serious psychiatric disorder. Forty-eight percent had been traumatized by severe family disruption, gross emotional deprivation or abuse during childhood. Seventy-nine percent lacked emotional support from the man responsible for the pregnancy, and the majority were experiencing overwhelming stress from the interplay of multiple problems exacerbated by their unwanted pregnancy. PMID- 1628718 TI - Delaying pelvic exams to encourage contraceptive use. PMID- 1628719 TI - Bisexual men and HIV infection. PMID- 1628720 TI - Sexually transmitted synergy. PMID- 1628721 TI - Increased oxidized methionine residues in BAL fluid proteins in acute or chronic bronchitis. AB - Phagocytic cells such as alveolar macrophages (AM) or polymorphonuclear neutrophils (PMN) in the bronchoalveolar tract are a potential source of the oxygen-derived free radicals which are presumed to be involved in lung tissue damage. Previous results have shown that the methionine sulphoxide (MET(O)) content of bronchoalveolar lavage fluid (BALF) protein is a reliable parameter to indicate oxidative processes in idiopathic pulmonary fibrosis (IPF). We measured the molar ratio between MET(O) and methionine (MET) in the BALF protein from healthy nonsmokers (control group), healthy smokers and patients with acute or chronic bronchitis (AB or CB). The MET(O)/MET ratio of the nonsmoking group (n = 11) was 0.046 +/- 0.008 (mean +/- SEM). Healthy smokers (n = 8) had similar values (0.042 +/- 0.008), even though they had strongly increased AM counts in BALF. Patients with AB (n = 12) showed an increased MET(O)/MET ratio (0.191 +/- 0.031) and had high PMN but normal AM counts in BALF. Patients with CB (n = 13) showed an increase in the MET(O)/MET ratio (0.086 +/- 0.010) and moderately increased PMN and markedly increased AM counts. Taking all results together, the MET(O)/MET ratio correlated positively with the relative PMN number (r = 0.70; p less than 0.0002) and inversely with the relative AM number (r = 0.67; p less than 0.0002). In the group with CB, the MET(O)/MET ratio correlated inversely with forced expiratory volume in one second (FEV1) % pred. (r = -0.77) and FEV1/inspiratory vital capacity (IVC) % pred. (r = -0.89).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628722 TI - Bronchodilator reversibility, exercise performance and breathlessness in stable chronic obstructive pulmonary disease. AB - Partial bronchodilator reversibility can be demonstrated in many patients with stable chronic obstructive pulmonary disease (COPD), but its relevance to exercise capacity and symptoms is uncertain. Previous data suggest that anticholinergic bronchodilators do not improve exercise tolerance in such patients. We studied 32 patients with stable COPD, mean age 65 yrs, in a double blind, placebo-controlled, cross-over trial of the inhaled anticholinergic drug, oxitropium bromide. From the within and between day placebo spirometry, we derived the spontaneous variation in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) of this population (FEV1 140 ml; FVC 390 ml) and considered responses beyond this to be significant. Oxitropium bromide increased baseline FEV1 from 0.70 (0.28) l (mean (SD)) to 0.88 (0.36) l. The 6 min walking distance increased by 7% compared with placebo, whilst resting breathlessness scores fell from 2.0 to 1.23 at rest and 4.09 to 3.28 at the end of exercise after the active drug. Improvements in walking distances and symptoms were unrelated to changes in either FEV1 or FVC, indicating that routine reversibility testing is not a good predictor of symptomatic benefit in these patients. PMID- 1628723 TI - Pneumocystis carinii pneumonia in HIV-infected patients: diagnostic yield of induced sputum and immunofluorescent stain with monoclonal antibodies. AB - The purpose of this study was to evaluate the diagnostic yield of induced sputum (IS), assessing the reliability of indirect immunofluorescent stain with monoclonal antibodies (IFMoAb) and methenamine silver (Met-Ag) and analysing factors likely to influence the sensitivity of these techniques. An analysis was prospectively carried out on IS specimens collected from 61 human immunodeficiency virus (HIV)-infected patients during 69 episodes of suspected Pneumocystis carinii pneumonia. Ultrasonic nebulizers with hypertonic 2% saline were used. IFMoAb to P. carinii and Met-Ag were performed after cytocentrifugation of the specimen. Results were compared with those of bronchoalveolar lavage (BAL) with/without transbronchial biopsy (TBB), performed not more than seven days after induction of sputum. P. carinii pneumonia was confirmed in 32 episodes, of which IS was diagnostic in 23. The sensitivity of the staining procedures was 69% for IFMoAb, and 28% for Met-Ag. The three episodes of P. carinii pneumonia in patients on oral chemoprophylaxis yielded negative IS results; in contrast, IS was negative in only 6 of the 29 cases not receiving chemoprophylaxis. IS is a non-aggressive procedure that diagnosed P. carinii pneumonia in 72% of our cases. The yield increased significantly when IFMoAb was used in patients not receiving oral chemoprophylaxis. PMID- 1628724 TI - Lung function impairment following mycoplasmal and other acute pneumonias. AB - We prospectively studied the lung function of 106 consecutive young patients with pneumonia. At the time of hospital admission we observed impaired spirometric function in 48% of the patients. During and following treatment, the frequency of abnormalities in pulmonary function tests decreased rapidly. However, at the 15th day of hospitalization, abnormal ventilatory function was still demonstrated in 21% of the patients. Such prolonged impairment of ventilatory function was significantly more likely to result from pneumonia caused by Mycoplasma pneumoniae than from forms caused by adenovirus or Streptococcus pneumoniae. PMID- 1628725 TI - Branhamella catarrhalis respiratory infections. AB - Branhamella catarrhalis is an aerobic Gram-negative diplococcus. It has been traditionally regarded as an oropharyngeal commensal and until recently was only identified as a pathogen in cases of bronchopulmonary infections. The aim of this study was to analyse the characteristics of the respiratory infections caused by B. catarrhalis and to know the antibiotic susceptibility of this microorganism. We retrospectively studied 32 lower respiratory tract infections, caused by B. catarrhalis (20 cases of bronchial infection and 12 cases of pneumonia), diagnosed between 1988-1989 in our hospital. All patients had an underlying disease; chronic obstructive pulmonary disease (COPD) and chronic heart disease being the most frequent. The aetiological diagnostic procedures were: sputum culture in 28 cases (15 in pure culture and 13 mixed), protected specimen brush (PSB) in three cases and transthoracic needle aspiration (TNA) in one case. Twenty B. catarrhalis isolates were penicillin and ampicillin-resistant, 11 in the pneumonia group and 9 in the bronchial infection group. All isolates were sensitive to amoxycillin-clavulanic acid and second generation cephalosporin. In our group four patients died. We conclude that B. catarrhalis is a not infrequent cause of respiratory infection, particularly in COPD patients, and that the high incidence of antibiotic resistance to penicillin and ampicillin should be taken into account before considering an empirical antibiotic treatment. PMID- 1628726 TI - Towards a quantitative description of asthmatic cough sounds. AB - This study describes a method of quantitatively characterizing cough sounds using digital signal processing techniques. Differences between asthmatic and non asthmatic cough sounds are presented. Coughs from 12 asthmatic and 5 non asthmatic subjects were analysed. Cough sounds and flows were digitized, at a sampling rate of 5 kHz, before and after a free-running exercise test. Individual coughs were divided into two or three phases, corresponding to the initial glottal opening burst, the quieter middle phase, and (sometimes) the final closing burst. Standard signal processing techniques were then invoked to characterize the spectral and temporal shapes of the first two phases. Factor analysis indicated that the spectral shapes of the two phases are independent, with each being largely described by the degree of "peakedness" in the spectrum, and by the balance of energy between low and high frequencies. Both the duration of the initial burst and zero-crossing rates of the cough waveform (which indicates the "spectral balance") during each of the first two phases were smaller for asthmatic than for non-asthmatic coughs. Fewer asthmatic coughs contained a final burst. Discriminant analysis between the two groups gave classification error rates of 20-30%. The peak flow recorded during the cough was significantly smaller for asthmatics, and correlated very well with the peak flow recorded during forced expiration. Thus, significant differences exist between asthmatic and non-asthmatic cough sounds. An effective representation of the temporal structure of the cough sound is required to successfully characterize the cough. PMID- 1628727 TI - Repeated inhalation of bradykinin attenuates adenosine 5'-monophosphate (AMP) induced bronchoconstriction in asthmatic airways. AB - Repeated bronchial challenges with inhaled bradykinin lead to a rapid loss of the bronchoconstrictor response and this has been suggested to be due to depletion of contractile neuropeptides from sensory nerve endings. If adenosine 5' monophosphate (AMP), another potent bronchoprovocant in asthma, and bradykinin share a common pathway in inducing bronchoconstriction in asthmatic subjects, then repeated bradykinin bronchoprovocation tests should reduce the response to subsequent inhalation of AMP. We examined this hypothesis in eight asthmatic subjects in a double-blind, randomized study. On the histamine study day, two consecutive concentration-response studies with inhaled histamine were followed by a third consecutive challenge with AMP and the provocation concentration producing a 20% fall in forced expiratory volume in one second from the post diluent baseline value (PC20 FEV1) for this agonist was calculated. On the bradykinin study day, two consecutive bronchoprovocation tests with bradykinin were followed by a third inhalation challenge to obtain the PC20AMP value. On a further occasion, the asthmatic subjects underwent two consecutive concentration response studies with inhaled bradykinin followed by a third consecutive challenge with histamine. On the histamine study day, the geometric mean PC20AMP value was 28.1 mg.ml-1, whilst on the bradykinin study day, the fifteenfold reduction in bradykinin responsiveness after the second bradykinin challenge was accompanied by a significant reduction of the airway responsiveness to AMP, the PC20AMP being 59.8 mg.ml-1. A similar reduction in bradykinin responsiveness failed to alter the airway response to a subsequent inhalation with histamine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628729 TI - Isolation of phenotypically and functionally distinct macrophage subpopulations from human bronchoalveolar lavage. AB - Bronchoalveolar lavage was used to obtain alveolar macrophages (AM) from the lower respiratory tract of healthy normal volunteers. Monoclonal antibody (MoAb) probes specific against macrophage determinants were then applied, in conjunction with density separation techniques, to identify and isolate three relatively homogeneous subpopulations from the AM pool. The MoAbs used, RFD1 and RFD7, have previously been shown to differentiate between "dendritic" cells and mature macrophages, respectively, in normal tissue. In addition to these two phenotypically distinct AM subsets (RFD1+D7- and RFD1-D7+ AM), a third AM subpopulation was isolated, which appeared to express both markers (RFD1+D7+). All three separated macrophage subsets were morphologically similar but exhibited distinct differences in surface receptor expression, enzyme content and physiology. Isolated RFD1+D7- AM (the phenotype of "dendritic" cells) did not adhere to the glass, had weak expression of C3b and FcR1 receptors, low fibronectin content and lysosomal activity; only a small proportion of these cells exhibited phagocytosis. The other two isolated AM subsets adhered to glass, expressed C3b and FcR1 receptors, had high fibronectin and acid phosphatase content, and a large majority exhibited phagocytic capacity; qualitative and quantitative differences in these features existed between the two AM subtypes. Furthermore, a diverse spectrum of hexose monophosphate shunt activity was observed throughout all three AM subpopulations, with the highest activity being recorded in the non-adherent AM. These data support the concept of a dynamic heterogeneity within the AM population. The variation in surface antigen expression and physiological capabilities observed amongst the three isolated AM subsets implies the presence of functionally distinct AM within the human lung, which, during steady-state conditions, may be critically balanced under the influence of stimuli in their local microenvironment. In support, proportional and functional shifts have been witnessed amongst these three AM subpopulations with the advent of disease. PMID- 1628728 TI - No influence of airway heat flux on airflow-induced bronchospasm. AB - We used a canine model of airway reactivity to examine the role of airway heat flux in the response to dry air challenge. Airflow-induced bronchospasm (AIB) was assessed by measuring collateral system resistance (Rcs) with a wedged bronchoscope technique in anaesthetized mechanically ventilated dogs. We manipulate post-challenge airway heat flux by exposing peripheral airways to cool dry air (23.9 +/- 0.3 degrees C, 0.8 +/- 0.2 mgH2O.l-1), cool humid air (24.2 +/- 0.2 degrees C, 21.5 +/- 0.3 mgH2O.l-1), or warm humid air (35.3 +/- 0.4 degrees C, 40.6 +/- 0.3 mgH2O.l-1) during the recovery period (n = 14) following a high flow challenge (1,500 ml.min-1 for 2 min) with cool dry air. In a second series of experiments (n = 6), we attempted to further exaggerate airway heat flux during challenge by exposing peripheral airways to warm humid air during both baseline and recovery periods. In comparison to control (i.e. treatment with cool dry air before and after challenge), treatment with warm humid air during recovery period produced a small but significant attenuation (p less than 0.01) in Rcs. Cool humid air during recovery had no affect on Rcs following challenge. Warm humid air during both baseline and recovery tended to attenuate Rcs after challenge (p less than 0.05). We conclude that airway heat flux in itself has no significant physiological affect on AIB in the canine lung periphery. PMID- 1628730 TI - Fractional processing of sequential bronchoalveolar lavage fluid from intubated babies. AB - Two groups of intubated newborn babies were studied to determine the clinical effects of interrupted bronchoalveolar lavage (BAL) by suction catheter (S-BAL) and the similarities to adult fibreoptic BAL of fractional processing of sequential lavage fluid (BALF). Both groups were lavaged by two aliquots of 1 ml.kg-1, instilled via a blindly placed suction catheter, wedged on two separate insertions through the right main bronchus. In 14 infants, (sequential lavage group), BALF aliquots were analysed separately. There were no differences in the volumes recovered or total cell counts between the first and second BALF aliquots. Where cell morphology was visible (n = 11), the percentage of macrophages, but not the absolute number, increased in the second BALF aliquot (p less than 0.01). BALF urea and epithelial lining fluid volume estimated by urea dilution were similar between the two aliquots (n = 8). In a separate group (blood gas group), vital signs were recorded in 10 infants undergoing S-BAL. At 1 min after lavage there was a rise in mean arterial blood pressure (39 vs 49.5 mmHg, p less than 0.05) and a fall in transcutaneous oxygenation (10.6 vs 7.5 kPa, p less than 0.05). Recovery was present at 3 min post-S-BAL, but mean blood pressure remained elevated (39 vs 45 mmHg, p less than 0.05) and transcutaneous oxygen continued to be lower when compared to baseline values (10.6 vs 9.2 kPa, p less than 0.05). S-BAL of intubated infants appears to sample both the proximal and distal airways and results in changes in vital signs similar to routine non selective endotracheal suctioning. PMID- 1628731 TI - Pulmonary function in childhood connective tissue diseases. AB - The term connective tissue diseases (CTD) defines a group of illnesses characterized by the presence of immune abnormalities and by widespread inflammation involving various organs and tissues including the lung. These diseases are not frequent in the paediatric age group. Very few data on pulmonary function are available in paediatric CTD. We investigated possible early lung function abnormalities and any likely relationship with clinical activity of the disease in a group of 81 paediatric CTD patients, without clinical or radiological evidence of pulmonary involvement. Measurement of lung volumes and diffusion lung capacity were performed. A sample of 65 subjects, defined as normal on the basis of history and clinical examination, and matched by age and height with the group of patients, was chosen as control group. CTD patients did not show significant deviations from the control distribution with respect to functional residual capacity (FRC) and maximal expiratory flow at 75% of the forced vital capacity (MEF75) values. On the contrary, both vital capacity (VC) and diffusing capacity of the lungs for carbon monoxide (DLCO) were quite impaired in most CTD during the active phase of the disease. Our results show a functional lung impairment in most children with clinically active CTD, even in absence of abnormalities on chest X-ray pictures. PMID- 1628733 TI - Mucus clearance with three chest physiotherapy regimes in cystic fibrosis: a comparison between postural drainage, PEP and physical exercise. AB - The effects of three different regimes of chest physiotherapy were compared in this cross-over study. Mucus clearance was monitored in nine clinically stable cystic fibrosis (CF) patients. The patients performed: 1) postural drainage with thoracic expansion exercises + forced expiration technique (FET) in the left decubitus position; 2) positive expiratory pressure (PEP)-mask breathing + FET; and 3) physical exercise on a bicycle ergometer + FET. All treatments had the same duration and FET was standardized. Mucus clearance was assessed using a technique based on measurement of the elimination of inhaled radiolabelled particles. Mean clearance of tracer from the right lung by postural drainage, PEP and physical exercise was 18% (range 10-29%), 20% (12-43%), 16% (8-25%), respectively, and from the left lung 20% (8-42%), 15% (5-23%) and 13% (5-17%), respectively. The differences were not statistically significant. Surprisingly, postural drainage (PD) was the most effective technique in the left, dependent lung in 7 of the 9 patients. PMID- 1628732 TI - Growth factor activity in the lung during compensatory growth after pneumonectomy: evidence of a role for IGF-1. AB - Unilateral pneumonectomy in rats causes compensatory growth of the remaining lung. During this growth, there are large increases in the cell numbers and in the rates of collagen and non-collagen protein production. We examined possible mechanisms by which these changes might occur. Assessment of the effect of bronchoalveolar lavage (BAL) fluid on fibroblasts in vitro demonstrated the presence of stimulatory activity for fibroblast replication in control animals. This activity was greatly increased two and six days postpneumonectomy (115 +/- 26% and 75 +/- 18% above control values, respectively), but had returned to normal by 14 days. Preliminary characterization suggests that the activity is heat labile and consists of at least two moieties with apparent molecular weights of 5-15 kD and 70-220 kD. The activity was partially blocked by antibodies to insulin-like growth factor-1 (IGF-1), and levels of IGF-1 were increased by about 100% (p less than 0.001) two days after pneumonectomy compared with control values. Examination of BAL cells demonstrated an early influx of leucocytes into the remaining lung of pneumonectomized rats. At two days, about 25% of the lavageable cells were neutrophils, but macrophages were the predominant cell type at all times. The extravascular albumin space of the lung increased by about 65% (p less than 0.01), six days after pneumonectomy. The influx of circulatory proteins and cells are potential sources of the increased mitogenic activity observed in the lung. PMID- 1628734 TI - Hypoxaemia and liver cirrhosis: a new argument in favour of a "diffusion perfusion defect". AB - Liver cirrhosis is sometimes associated with very severe hypoxaemia, which is thought to be the result of intrapulmonary vascular dilatations (IPVDs). These vascular abnormalities, although close to the gas exchange units, are so dilated that diffusion of oxygen molecules to their centre is impaired, causing an increase in alveolar-arterial oxygen tension difference (P(A-a)O2). On the other hand, administration of 100% oxygen provides enough driving pressure to overcome this relative diffusion defect and rules out a true intrapulmonary shunt. We report a case in which, in spite of a normal increase in arterial oxygen tension (PaO2) under 100% oxygen, exercising results in a marked impairment of oxygen exchange and a large intrapulmonary shunt. This is probably due to the increased cardiac output and preferential blood flow through these low resistance IPVDs. PMID- 1628735 TI - Endothelial modulation of pulmonary vascular tone. AB - Pulmonary endothelial cells normally synthesize prostacyclin (PGI2) and nitric oxide (NO), which are both potent vasodilators. Although PGI2 is largely used to treat patients with severe pulmonary hypertension, its role in the physiology and pathophysiology of the pulmonary circulation is still debated. NO, which is now considered as the endogenous nitrovasodilator, is perhaps more involved than PGI2 in the mechanisms that modulate pulmonary vascular tone in health and disease. There is evidence to suggest that background release of NO contributes to the normally low pulmonary vascular tone in normoxia. Although there are theoretical grounds to hypothesize that hypoxia reduces the synthesis of NO, lack of the latter does not seem to account for the acute hypoxic pulmonary vasoconstriction. Instead, there is evidence to suggest that NO activity is increased in order to modulate the pulmonary vasopressor response to acute alveolar hypoxia. However, more consistent, concerning the role of NO, are data gathered from studies performed in chronic hypoxic conditions. Both experimental data and studies performed in man demonstrate impairment of NO synthesis and/or release in chronic hypoxic pulmonary hypertension. The impaired NO production, whilst reducing the ability of the pulmonary vasculature to relax, also favours the occurrence of excessive pulmonary vasoconstriction. Lack of NO synthesis might also permit mitogenesis and proliferation of various cell types within the vascular wall. We hypothesize that functional alterations of pulmonary endothelium are likely to affect both reactivity and growth of pulmonary vessels. In this respect, NO probably has a pivotal role in modulating pulmonary vascular tone and controlling pulmonary vascular remodelling in health and disease. PMID- 1628736 TI - Extended thoracoscopy: a biopsy method to be used in case of pleural adhesions. AB - Extended thoracoscopy (ET) allows several large biopsies to be taken in patients with thick adhesions of the pleura when normal thoracoscopy is impossible. Twenty patients with undiagnosed pleural effusion or thickening and two with associated pulmonary tumour close to the chest wall underwent ET because closed adhesions prevented the induction of an artificial pneumothorax. Under local anaesthesia and neuroleptanalgesia, at the site of suspected lesions on computed tomographic (CT) scan, a cutaneous incision of 3-4 cm is made on the appropriate intercostal space. After dissection with blunt scissors, the operator introduces his finger to create a space in the pleural cavity. The thoracoscope is inserted to inspect the pleura and to take several biopsies for histopathological examination. A chest tube is inserted for a few minutes after checking airtightness and haemostasis. The procedure is well-tolerated. In three cases no pleural biopsy could be taken; in three patients a false negative diagnosis was observed. A correct diagnosis was obtained in 16 out of 19 patients (84%). If performed by a pulmonologist experienced with thoracoscopy ET is a rapid, safe and efficient method to obtain biopsies in cases where normal thoracoscopy after induction of a pneumothorax is not possible. It considerably reduces the need for open thoracotomy. PMID- 1628737 TI - Intrathoracic tumour. PMID- 1628738 TI - Mitogen-induced expression of the primary response gene cMG1 in a rat intestinal epithelial cell-line (RIE-1). AB - cMG1 is a primary response gene first identified in a rat intestinal epithelial (RIE-1) cell-line [(1990) Oncogene 5, 1081-1083]. A number of mitogens, including epidermal growth factor (EGF), angiotensin II (AII), serum and insulin rapidly induced 2- to 6-fold increases of cMG1 mRNA in RIE-1 cells, while transforming growth factor-beta caused a small reduction. Cyclic AMP-elevating agents blocked the increase of cMG1 mRNA induced by EGF. The AII-stimulated increase of cMG1 mRNA was blocked by the depletion of protein kinase C, whereas the EGF-stimulated increase was not affected, indicating that protein kinase C-dependent and independent signalling pathways stimulate cMG1 expression. PMID- 1628739 TI - Ordered phosphorylation of p42mapk by MAP kinase kinase. AB - Preparation of milligram amounts of [32P]p42mapk, phosphorylated at Tyr185 or diphosphorylated at Tyr185/Thr183, for use as specific protein phosphatase substrates is described. Tyr- but not Thr-phosphorylated p42mapk, accumulates when ATP is limiting. Furthermore, Tyr185-phosphorylated p42mapk exhibits an apparent 10-fold decrease in apparent Km (46.6 +/- 6.6 nM) for MAP kinase kinase compared to that for the dephospho form (approximately 476 nM). We conclude that Tyr185 precedes Thr183 phosphorylation, and that this is prerequisite, dramatically increasing the affinity of p42mapk for MAP kinase kinase. PMID- 1628740 TI - Expression of blood clotting factor VIII:C gene in capillary endothelial cells. AB - The essential role of Factor VIII:C (FVIII:C, anti-hemophilia factor A) as a cofactor for Factor IXa-dependent activation of Factor X has been established. In this paper, we describe that capillary endothelial cells from bovine adrenal medulla express active FVIII:C gene. Accumulation of FVIII:C in conditioned media from an 8-day-old culture is approximately twice as high as that stored in the cell when immunoprecipitated FVIII:C was analyzed for its ability to convert Factor X to Factor Xa. Analysis of [35S]methionine-labeled and immunoprecipitated FVIII:C from cells or conditioned media on SDS-PAGE under fully denatured conditions indicated that the newly synthesized FVIII:C consists of heavy chain of M(r) 200,000 and light chain of M(r) 46,000. The secreted FVIII:C in the non reduced condition however, has a molecular weight of 270,000 which suggests that in native protein, the heavy and light chains are held together by S-S bonds. Furthermore, susceptibility of the immunoprecipitated FVIII:C to N-glycanase digestion establishes that the endothelial cells derived FVIII:C contains asparagine-linked carbohydrate side chains. PMID- 1628741 TI - Alcohol dehydrogenase (ADH). Influence of homo- and heterologous ADH administration on albino rats craving for alcohol and on ADH isozyme activity in the liver. AB - The effects of homo- and heterologous alcohol dehydrogenase (ADH) administration into albino rats were investigated. It was found that homologous ADH increases and heterologous ADH decreases the craving for ethanol. The latter effect was accompanied by the appearance of anti-ADH-3 antibodies and by a decrease in ADH-3 activity in the liver. Craving for alcohol decreased after both active and passive immunization against ADH. PMID- 1628742 TI - Differential inhibition of abortive transcription initiation at different promoters catalysed by E. coli RNA polymerase. Effect of rifampicin on purine or pyramidine-initiated phosphodiester synthesis. AB - The action of rifampicin on the RNA chain initiation catalysed by E. coli RNA polymerase over different templates has been studied. The steady-state formation of dinucleoside tetraphosphate under the condition of abortive initiation reaction was assayed. It was observed that rifampicin shows a spectrum of inhibitory effects on transcription initiation at different promoters. At two different promoters with a pyrimidine nucleotide at the 5'-initiation site, e.g. rrnB P2 having CTP and lacP2 having UTP, the effect of rifampicin on the abortive synthesis of the first phosphodiester bond was found to be total, even at low concentrations of the antibiotic. On the other hand, in most cases the effect of rifampicin on the abortive synthesis with a purine nucleotide at the 5' initiation site was found to be only partial, with the exception of the T7A2 promoter, where rifampicin stimulates the abortive synthesis of pppGpC. It was also noticed that if there was a purine nucleotide at the second position of a dinucleotide which had already been synthesised by the enzyme, then further addition of the third nucleotide was not blocked in the presence of rifampicin. It appeared that a purine nucleotide at the initiation site or at the product terminus site of a translocated dinucleotide behaved similarly towards rifampicin. In the same way, if this position was occupied by a pyrimidine, rifampicin would inhibit further phosphodiester synthesis, even at a very low concentration. The stimulatory effect of rifampicin at the T7A2 promoter was presumably because here a ternary complex containing the promoter, enzyme and the abortive transcript pppGpC was initially stable, but dissociated upon addition of rifampicin, resulting in the rapid turn-over of the product. PMID- 1628743 TI - Characteristic differences in the mode of quinone reduction and stability between energy-coupled and -uncoupled NADH-quinone reductases from bacterial respiratory chain. AB - Bacterial respiratory chain has two types of NADH-quinone reductase (NQR): one is energy-coupled (type-1) and the other had no energy-transducing capacity, that is, energy-uncoupled (type-2). Each of the NADH-reacting flavoprotein subunits of NQR-1 from Escherichia coli and the marine Vibrio alginolyticus reduced quinone to semiquinone radicals by the one-electron transfer pathway and was very sensitive to preincubation with NADH. On the other hand, the NQR-2 from these bacteria reduced quinone to quinol by the two-electron transfer pathway and was insensitive to preincubation with NADH. Since the NQR-1 from E. coli functions as a proton pump, whereas that from the marine V. alginolyticus functions as a sodium pump, the formation of semiquinone radicals as an intermediate is likely to be a common mechanism to functioning as either proton or sodium pump. PMID- 1628744 TI - Phosphorylation and inactivation of HMG-CoA reductase at the AMP-activated protein kinase site in response to fructose treatment of isolated rat hepatocytes. AB - We have previously shown that incubation of isolated hepatocytes with fructose leads to elevation of AMP and activation of the AMP-activated protein kinase. We now show that this treatment causes marked inactivation of HMG-CoA reductase. Using immunoprecipitation from the microsomal fraction of 32P-labelled cells, we also show that this treatment leads to a 2.6-fold increase in the phosphorylation of the 100 kDa subunit of HMG-CoA reductase. Successive digestion of this 32P labelled subunit with cyanogen bromide and endoproteinase Lys-C confirmed that Ser-871, the site phosphorylated in cell-free assays by the AMP-activated protein kinase, was the only site phosphorylated under these conditions. PMID- 1628745 TI - Natural polypeptides in left-handed helical conformation. A circular dichroism study of the linker histones' C-terminal fragments and beta-endorphin. AB - Circular dichroism has been used to investigate the histone H1 and H5 C-terminal fragments and beta-endorphin conformation. It has been shown that in aqueous solution these polypeptides preferably adopt the left-handed helical conformation of the poly-L-proline II type. A break in the linear temperature dependence of the CD value was found in the temperature interval between 50 and 55 degrees C. It was proposed to be due to non-cooperative disordering of the conformation caused by the destruction of the hydration shell. PMID- 1628746 TI - Transfer of a chloroplast-bound precursor protein into the translocation apparatus is impaired after phospholipase C treatment. AB - We have studied the influence of phospholipase C treatment of intact purified chloroplast on the translocation of a plastid destined precursor protein. Under standard import conditions, i.e. in the light in the presence of 2 mM ATP translocation was completely abolished but binding was observed at slightly elevated levels. An experimental regime which allowed binding but not import of the precursor protein, i.e. in the dark in the presence of 10 microM ATP, demonstrated that translocation intermediates, normally detected at this stage, were missing in phospholipase treated chloroplasts. The precursor was completely sensitive to protease treatment, indicating that the transfer of the precursor from the receptor to the import apparatus was blocked by phospholipase treatment. PMID- 1628747 TI - A TIM barrel protein without enzymatic activity? Crystal-structure of narbonin at 1.8 A resolution. AB - The major protein component in seeds is storage protein. These have no known enzymatic activity and act to provide amino acids as a source of metabolites in the developing seedling. We report here the first three dimensional crystal structure of a seed storage globulin at high resolution. The molecule of the 2S globulin, narbonin, from Vicia narbonensis L., consists of an eight-stranded parallel alpha/beta barrel structure similar to that observed in triose phosphate isomerase (TIM). Narbonin is the first protein with this topology possessing no known enzymatic activity. Because of the lack of sequence information most of the primary structure was determined directly from the electron density. PMID- 1628748 TI - Embryology of the eye and its adnexae. AB - The embryonal and fetal development of the human eye includes a series of sequential events starting with the fertilization of the ovum and culminating in the birth of a normal baby. Three main periods can be distinguished in the prenatal development of the eye. The first period called embryogenesis is characterized by the establishment of the primary organ rudiments and ends at the end of the 3rd week with the appearance of the optic sulci on both sides of the midline at the expanded cranial end of the still open neural folds. The second period called organogenesis includes the development of the primary organ rudiments and extends till the end of the 8th week. The third period involves the differentiation of each of the primitive organs into a fully or partially active organ and is called differentiation. The period of embryogenesis is characterized by the appearance and migration of the neural crest cells and by the formation of the primary brain vesicles. The period of organogenesis extends from the 4th week till the end of the 8th week. The 4th week shows the closure of the neural canal anteriorly with the subsequent evagination of its lateral wall into optic vesicles, the invagination of the lower nasal wall of the optic vesicle causing the formation of the optic cup, and the development of the lens plate, retinal disk and embryonic fissure. The embryonic fissure extends into the optic stalk which connects the cavity of the optic vesicle with the cavity of the neural canal; the hyaloid artery penetrates into the optic cup through the embryonic fissure. During the 5th week, the optic cup is concluded, and the cells of its external layer acquire pigmentation as a result of contact with developing capillaries in the periocular mesenchyme; these capillaries anastomose with each other and form anteriorly the annular vessel. The lens plate develops into a lens pit and later into a lens vesicle which separates soon thereafter from the surface ectoderm. Inside the optic cup, the hyaloid vessels form the capillaries of the posterior tunica vasculosa lentis and through the capillaries of the lateral tunica vasculosa lentis anastomose with the annular vessel. The primary vitreous forms and the surface ectoderm overlying the lens vesicle differentiates into a primitive corneal epithelium. The facial and orbital structures also develop at this stage. The 6th week shows the incipient differentiation of the inner layer of the optic cup into a sensory retina, the formation of the secondary vitreous, the transformation of the posterior cells of the lens vesicle into primary lens fibers, the development of the periocular vasculature and the appearance of the first eyelid folds and of the anlage of the nasolacrimal duct. However, the dominating factor is the closure of the embryonic fissure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1628749 TI - Retinoic acid, local cell-cell interactions, and pattern formation in vertebrate limbs. AB - Retinoic acid (RA), a derivative of vitamin A, has remarkable effects on developing and regenerating limbs. These effects include teratogenesis, arising from RA's ability to inhibit growth and pattern formation. They also include pattern duplication, arising as a result of the stimulation of additional growth and pattern formation. In this review we present evidence that the diverse effects of RA are consistent with a singular, underlying explanation. We propose that in all cases exogenously applied RA causes the positional information of pattern formation-competent cells to be reset to a value that is posterior ventral-proximal with respect to the limb. The diversity of outcomes can be seen as a product of the mode of application of exogenous RA (global versus local) coupled with the unifying concept that growth and pattern formation in both limb development and limb regeneration are controlled by local cell-cell interactions, as formulated in the polar coordinate model. We explore the possibility that the major role of endogenous RA in limb development is in the establishment of the limb field rather than as a diffusible morphogen that specifies graded positional information across the limb as previously proposed. Finally, we interpret the results of the recent finding that RA can turn tail regenerates into limbs, as evidence that intercalary interactions may also be involved in the formation of the primary body axis. PMID- 1628750 TI - Positive and negative DNA elements of the Drosophila grimshawi s18 chorion gene assayed in Drosophila melanogaster. AB - Germ line transformation has been used to map the cis regulatory DNA elements responsible for the precise and evolutionarily stable developmental expression of the s18 chorion gene. Constructs containing chimeric combinations of Drosophila melanogaster and D. grimshawi DNA regions, as well as D. grimshawi sequences alone, can direct expression in the follicular epithelium, in an s18-specific temporal and spatial pattern. The results indicate that both positive and negative regulatory elements can function when transferred from D. grimshawi to D. melanogaster. The first ca. 100 bp of the 5'-flanking DNA region constitute a minimal, developmentally regulated promoter, expression of which is inhibited by the next 100-bp DNA segment and activated by positive elements located further upstream. Expression of the minimal promoter can also be enhanced by more distant chorion regulatory elements, provided the inhibitory DNA segment is absent. PMID- 1628751 TI - Cell mixing in the spinal cords of mouse chimeras. AB - With the aim of determining whether there is significant cell mixing during development of the spinal cord, experimental chimeric mice containing two genetically distinct cell populations were produced by aggregating BALB/c or BALB/c x LPT hybrid embryos with C3H/HeN embryos. The BALB/c and LPT hybrid spinal cord cells were distinguished histochemically from the C3H/HeN spinal cord cells by using beta-glucuronidase as an independent cell genotype marker. BALB/c and LPT hybrid cells have high levels of beta-glucuronidase activity, while the C3H/HeN cells have low levels. The spinal cords of the chimeras were dissected out regionally (i.e., cervical, thoracic, and lumbar areas) and were sectioned serially. Each region was then analyzed by scoring large- and medium-sized neuronal cell bodies (greater than or equal to 10 microns) whose genotypes were distinguished by their beta-glucuronidase levels. Observations of seven chimeric mice, with coat colors that varied from one extreme (5% albino) to the other (90% albino), suggest that each chimeric spinal cord is a relatively homogeneous population throughout its length. On average only 4 to 5 percentage point differences were observed when comparing left-right, cranial-caudal, and dorsal ventral regions within a given chimera. The cell mixing, however, is not total, and regional variations were noted. Maximum left-right differences between different spinal cord levels never exceeded 18 percentage points, while in the entire cord the maximum left-right difference was 11 percentage points. When considering dorsal-ventral differences, 18 and 15 percentage points were observed within the spinal cord levels and the entire cord, respectively. However, when comparisons were made between smaller subregions (e.g., right-dorsal-cervical vs left-ventral-lumbar), larger differences of up to 30 percentage points were observed. In addition, the genotype proportions in the spinal cord were closely correlated with the visually estimated proportions of coat color genotypes. PMID- 1628752 TI - Temporal pattern of synthesis of the mouse cortical granule protein, p75, during oocyte growth and maturation. AB - We previously demonstrated that a protein of M(r) 75,000 (p75) is localized to cortical granules (CGs) in mouse oocytes and eggs and is released upon activation or fertilization of eggs (K.E. Pierce, M. C. Siebert, G. S. Kopf, R. M. Schultz, and P. G. Calarco, 1990, Dev. Biol. 141, 381-392). To examine the temporal pattern of synthesis of p75 during the early stages of CG formation, growing oocytes, which were isolated from juvenile mice, were incubated for 4 hr in medium containing [35S]methionine, and radiolabeled proteins were immunoprecipitated using an antiserum that detects p75. Synthesis of p75 is detected at low levels in the smallest oocytes examined (less than 20 microns). Synthesis of p75 relative to total protein synthesis increases about 12-fold during oocyte growth from the 20-40 microns size and then remains constant throughout the remaining period of oocyte growth (40-70 microns). In the fully grown, germinal vesicle (GV)-intact oocyte (70-80 microns), immunoprecipitated p75 comprises approximately 1.5% of the total amount of radiolabeled protein. Three hours after the transfer of these oocytes to a medium that supports resumption of meiosis and GV breakdown in vitro, oocytes subjected to a 1-hr labeling pulse display a 35% decrease in the relative level of p75 synthesis. By 15 hr of maturation, p75 synthesis was reduced to 14% of that in the fully grown, GV-intact oocyte and this is similar to the level of p75 synthesis in ovulated eggs. The level of p75 synthesis following in vitro translation of total egg RNA is only 38% lower than that obtained from total oocyte RNA. In addition, synthesis of p75 is observed following in vitro translation of oocyte, but not egg, poly(A)+ RNA. These results are consistent with p75 synthesis during oocyte maturation being under translational control. PMID- 1628753 TI - Rise and fall of crystallin gene messenger levels during fibroblast growth factor induced terminal differentiation of lens cells. AB - Explanted rat lens epithelial cells differentiate synchronously in vitro to lens fiber cells in the presence of basic fibroblast growth factor (bFGF). We have monitored the expression of the three rat crystallin gene families, the alpha-, beta-, and gamma-crystallin genes, during this process. The expression of these gene families is sequentially activated, first the alpha-crystallin genes at Day 1, then the beta-crystallin genes at Day 3, and finally the gamma-crystallin genes at Day 8. The steady state levels of alpha- and beta-crystallin mRNA are not affected by incubation with actinomycin D, suggesting that these mRNAs are stable. Nevertheless, all crystallin mRNAs disappear from the differentiated explants between Days 10 and 11, a process signaled by bFGF. At this time a novel abundant mRNA appears. Cloning and sequencing showed that this mRNA encoded aldose reductase. Our results suggest a novel model for the regulation of crystallin synthesis during lens cell differentiation: a gene pulse delivers a certain amount of stable mRNA, this mRNA is removed at a later stage of differentiation by a stage-specific breakdown mechanism. Each of these regulatory steps requires a signal from bFGF. PMID- 1628754 TI - Dynamic expression of a cell surface protein during rearrangement of epithelial cells in the Manduca wing monolayer. AB - The expression of cell surface protein 2F5 changes dynamically in space and time during morphogenesis of the Manduca wing pattern. Two cell types (generalized epithelial cells and scale precursors) rearrange within each of the two epithelial monolayers of the wing to form periodic rows of scale cells. These two monolayers also interact with each other during a brief period of adult development. Each cell type shows a different pattern of protein 2F5 expression during cell rearrangement and during interaction of the two wing monolayers. Before and after these morphogenetic movements of epithelial cells, the protein is expressed on only a small population of wing cells. In abdominal epithelia where scale cells are also present but are not arranged in periodic rows, the expression pattern of the surface protein is temporally and spatially very different. An earlier study (Nardi and Magee-Adams, Dev. Biol., 116, 278-290, 1986) had shown that basal processes only extend from epithelial cells during their period of rearrangement within a monolayer and during the transient apposition of the wing's upper and lower monolayers. The differential distribution of protein 2F5 on lateral surfaces and basal processes of scale precursor cells and generalized epithelial cells may account in part for their orderly segregation into alternating rows as well as for the transient interaction of the two wing monolayers. PMID- 1628755 TI - The l(1)ogre gene of Drosophila melanogaster is expressed in postembryonic neuroblasts. AB - Previous genetic studies showed that the wild-type function of the lethal (1) optic ganglion reduced (l(1)ogre) gene in Drosophila melanogaster was needed, apparently specifically, for the generation and/or maintenance of postembryonic neuroblasts, i.e., those neuroblasts in the optic formation centers (primordia of the adult optic lobes) and giant neuroblasts scattered over the periphery of cortices of the larval central nervous system (CNS). In the present study temporal and spatial specificity of l(1)ogre expression was investigated by in situ hybridization and also immunofluorescence with polyclonal anti-l(1)ogre antibodies. l(1)ogre protein was detected, as expected, in the optic formation centers and giant neuroblasts in the larval CNS. l(1)ogre expression, however, was not specific to these neuroblasts: expression was also detected in a wide range of tissues including the CNS at many developmental stages. Examination of transcriptional pattern indicates that l(1)ogre is expressed in derivatives of the ectoderm, endoderm, and mesoderm (but not in the germ line) in two developmental contexts: (i) during and shortly after the proliferative phase and (ii) during histolysis of some larval tissues. PMID- 1628756 TI - Expression of DNA ligases I and II during oogenesis and early development of Xenopus laevis. AB - We have analyzed the expression of DNA ligase I protein during oogenesis and early development of Xenopus laevis. The protein is already present in stage I oocytes and then accumulates throughout oogenesis to reach a steady state level by stage VI. It remains at this level at least until tadpole stage. In stage VI oocytes DNA ligase I protein is almost exclusively localized in the germinal vesicle. We have partially purified a DNA ligase II activity from stage VI oocytes, unfertilized eggs, and stage 8 embryos. An 80-kDa polypeptide can be specifically adenylated in all three purified extracts. It is not recognized by antibodies directed against DNA ligase I and is active on oligo(dT)-poly(rA) substrate. It could therefore represent DNA ligase II protein. The presence of both DNA ligases I and II in oocytes and embryos is inconsistent with the DNA ligase model that had been previously proposed for amphibia. PMID- 1628757 TI - Molecular aspects of regeneration in developing vertebrate limbs. AB - We review embryological as well as molecular evidence that emphasizes the idea that both the regenerate and the developing vertebrate limb bud utilize a similar set of signals that regulate pattern formation. Evidence is presented to implicate the Hox-7.1 gene in the developmental regulation of growth, differentiation, and positional assignment during limb outgrowth and the proposal is made that the expression of this gene governs the cellular activities within the progress zone during limb outgrowth. Finally, we review the limited information known about the regenerative capabilities of limb buds in organisms that cannot regenerate as adults. We content that a solution to the problem of regenerative failure among higher vertebrates will come progressively through a stepwise analysis of impaired regeneration associated with increasing developmental age. PMID- 1628758 TI - DNA synthesis in the early embryo of the nematode Ascaris suum. AB - We have used microspectrofluorimetry to measure the rate of DNA synthesis in the first two embryonic cell cycles of the parasitic nematode Ascaris suum. The S phase of the early Ascaris cell cycles occupies at most 1 hr; G2 phase is prominent and occupies approximately 11 hr; no G1 phase could be detected. These results contrast with our previous measurements made with embryos of the free living nematode Caenorhabditis elegans, in which the earliest cell cycles consist of simple alternations between S and M phases. PMID- 1628759 TI - Extracellular Mg2+ induces an intracellular Ca2+ wave during oocyte activation in the marine shrimp Sicyonia ingentis. AB - In contrast to most systems in which oocyte activation is triggered by the fertilizing sperm, Sicyonia ingentis oocytes are activated by seawater Mg2+ during spawning. S. ingentis oocytes were spawned into Mg(2+)-free seawater and microinjected with the fluorescent Ca2+ indicator Fluo-3 to study the effects of added Mg2+ on intracellular Ca2+ levels. The Mg2+ induced a wave of fluorescence across the oocyte that traveled at a speed of 13 +/- 3 microns/sec. Extracellular Ca2+ was not required for induction of the wave. Treatment with Ca2+ ionophore in Mg(2+)-free medium or a localized injection (0.3% oocyte volume) of 3-5 microM Ca2+ also initiated the wave; injection of 250 mM Mg2+ (up to 1.5% oocyte volume) had no effect. Microinjection of 750 microM EGTA (final) suppressed the Mg(2+) induced wave, while an identical concentration of EDTA had no inhibitory effect. Subsequent to the initial Mg(2+)-induced intracellular Ca2+ increase, a second Ca2+ increase was observed at approximately 15 min postspawning; the timing of this second increase appeared to be independent of when the Mg(2+)-induced wave was initiated, thus an event associated with spawning may be involved. While oocytes in normal seawater were monospermic, those in Mg(2+)-free seawater were polyspermic, suggesting a role for the Mg(2+)-induced Ca2+ wave in regulating sperm entry into the oocyte. PMID- 1628760 TI - Increased expression of tissue plasminogen activator and its inhibitor and reduced fibrinolytic potential of human endothelial cells cultured in elevated glucose. AB - In diabetic patients, elevated plasma levels of t-PA and PAI-1 accompany impaired fibrinolysis. To identify mechanisms for these abnormalities, we examined whether vascular endothelial cells exposed to high glucose upregulate t-PA and PAI-1 production and whether ambient PA activity is decreased concomitantly. In 17 cultures of human umbilical vein endothelial cells grown to confluency in 30 mM glucose, the t-PA antigen released to the medium in 24 h was (median) 52 ng/10(6) cells (range 10-384) and the PAI-1 antigen was 872 ng/10(6) cells (range 217 2074)--both greater (P less than 0.02) than the amounts released by paired control cultures grown in 5 mM glucose--29 ng/10(6) cells (range 7.5-216) and 461 ng/10(6) cells (range 230-3215), respectively. In the presence of high glucose, the steady-state levels of t-PA and PAI-1 mRNAs were increased correspondingly (median 142 and 183% of control, respectively, P less than 0.05); high glucose per se and hypertonicity contributed to the upregulation in additive fashion. The PA activity of conditioned medium from cultures exposed to high glucose was 0.4 IU/ml (range 0.2-0.6), which was significantly lower (P less than 0.02) than the PA activity of control medium (0.5 IU/ml, range 0.2-0.9). No difference was observed when comparing the PA activities of acidified conditioned media, expected to be depleted of inhibitors. Thus, high glucose coordinately upregulates endothelial t-PA and PAI-1 expression through effects exerted at the pretranslational level and enhanced by even mild degrees of hypertonicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628761 TI - Poly I:C accelerates development of diabetes mellitus in diabetes-prone BB rat. AB - We developed a new experimental model of accelerated diabetes mellitus in the genetically susceptible diabetes-prone BB rat with the administration of the IFN alpha inducer poly I:C. With this model, there was both an increased incidence and accelerated onset of insulin-dependent-diabetes in poly I:C-treated animals compared with saline-treated controls. All twelve rats administered poly I:C (5 micrograms/gm body weight 3 times/wk) developed diabetes by 57 days of age (100%) compared with 1 of 27 (3.7%) saline-treated controls. Furthermore, the development of diabetes was accelerated in the poly I:C-treated group (mean age +/- SE at onset 52.8 +/- 0.58 days) compared with saline-treated controls (89.3 +/- 2.4 days, P less than 0.01). Additionally, poly I:C-treated rats had higher mean serum IFN-alpha levels than saline-treated rats at weeks 2 and 3 of treatment (210 vs. 27 and 183 vs. 25 U/ml, respectively, P less than 0.001). Poly I:C treatment of 5 Wistar rats, the parental strain, which is not susceptible to diabetes, did not result in insulitis, diabetes, or hyperglycemia. The histopathologic findings of insulitis and decreased immunoreactive islet insulin in poly I:C-accelerated diabetic BB rats and in BB rats with spontaneous diabetes suggest a similar pathophysiology. PMID- 1628762 TI - Islet cell and thyrogastric antibodies in 633 consecutive 15- to 34-yr-old patients in the diabetes incidence study in Sweden. AB - The effect of age on ICA and thyrogastric antibodies at diagnosis of IDDM was evaluated in 633 consecutively diagnosed Swedish diabetic patients aged 15-34 yr and in 282 volunteers of the same age. ICAs were present in 61% (383 of 633) of the patients and in 2% (5 of 282) of control subjects. When the initial classification was considered, ICAs were detected in 69% (327 of 473) of patients with IDDM, 23% (19 of 83) of those with NIDDM, 50% (36 of 72) of those with unclassifiable diabetes, and 20% (1 of 5) of those with secondary diabetes. The frequency of ICA fell significantly (P less than 0.001) with age in IDDM patients from 77% (104/135) in those 15-19 yr old to 52% (50 of 96) in 30- to 34-yr-old IDDM patients. The low frequency of ICA in 30- to 34-yr-old IDDM patients was confined to men (42%, 28 of 66). The frequency of gastric (H+, K(+)-ATPase) antibodies was significantly (P less than 0.05) higher in IDDM patients (10%, 47 of 449) than in patients with NIDDM (3%, 3 of 80) and unclassifiable diabetes (4%, 3 of 72). In conclusion, the frequency of ICA at the diagnosis of IDDM in young adult subjects decreases with increasing age, particularly in men. The frequent finding of ICA in patients considered to have NIDDM or unclassifiable diabetes indicates that misclassification of diabetes is frequent in young adult patients recently diagnosed with diabetes. PMID- 1628763 TI - An explanation for the neutral effect of DR2 on IDDM susceptibility in central Italy. AB - Susceptibility to IDDM is strongly associated with HLA. Some HLA allelic combinations (haplotypes) can be found in most patients, whereas other haplotypes are encountered only rarely. It has been proposed that this difference in susceptibility depends on the absence (in the DR3 and DR4 haplotypes) or the presence (in the DR2 haplotype) of Asp57 in the DQ beta-chain. Data on southern European populations challenge this hypothesis because the DR2 haplotype has not been associated negatively with IDDM, as reported in northern European populations. This study on a selected panel of DR2-positive Italian IDDM patients shows that 19 of 21 (90.5%) DR2 haplotypes possess a non-Asp57 DQB allele. Moreover, the same non-Asp57 subtype has a comparatively high frequency (9/28, or 32.1%, DR2 haplotypes) also in the DR2-positive healthy Italian population. The difference between patients and control subjects is significant (P less than 0.0001). This is the largest series of DR2-positive patients analyzed so far. Comparison with cumulated data in various white populations shows a distinct northern European-to-southern European gradient. Toward southern Europe, the relative frequency of the non-Asp57 DR2 subtype increases. Concomitantly, the apparent protective effect of the DR2 haplotype disappears. Therefore, the observed differences in DR2-IDDM association in white populations can be explained adequately by the Asp57 hypothesis, which this study's data strongly support. PMID- 1628764 TI - Free radical activity and hemostatic factors in NIDDM patients with and without microalbuminuria. AB - In non-insulin-dependent diabetes mellitus (NIDDM) patients, microalbuminuria predicts early mortality, predominantly from cardiovascular disease. Increased free radical activity and abnormalities in hemostasis have been implicated in the development of vascular disease. Therefore, we measured markers of free radical activity (nonperoxide-conjugated diene isomer of linoleic acid [PL-9,11-LA'] and lipid peroxides expressed as malondialdehyde [MDA]) along with the hemostatic variables: fibrinogen, von Willebrand factor (vWf), plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (t-PA), and plasmin activity (B beta 15-42) in 24 NIDDM patients (12 patients with microalbuminuria and 12 without microalbuminuria) and in 12 age-matched control subjects. There were no differences in linoleic acid (PL-9,12-LA) concentrations between the three groups. PL-9,11-LA' was elevated in the microalbuminuric patients compared with control subjects (P less than 0.05), but there was no difference between the two diabetic groups. MDA was elevated in the microalbuminuric diabetic patients compared with those patients without microalbuminuria (P less than 0.05) and control subjects (P less than 0.001). MDA was also increased in the patients without microalbuminuria compared with control subjects (P less than 0.01). Except for B beta 15-42, all the hemostatic variables were increased (P less than 0.05) in the diabetic patients compared with control subjects. The microalbuminuric diabetic patients had further increases in vWf (P less than 0.03) and t-PA (P less than 0.03) compared with patients with microalbuminuria. Our study suggests that there is an increase in free radical activity and abnormalities in hemostatic variables favoring a hypercoagulable state in NIDDM, especially in those with microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628765 TI - Susceptibility to IDDM in a Chinese population. Role of HLA class II alleles. AB - MHC associations with IDDM in a Chinese population were studied to investigate genetic susceptibility to the disorder. The frequency of HLA-DR3 was significantly higher in the diabetic patients (19/49 [38.7%] vs. control subjects, 11/105 [10.5%], Pc less than 1.3 x 10(-3), RR = 5.3 [CI 2.3-12.1]), whereas DR4 was not (11/49 [22.4%] vs. 28/105 [26.7%], NS). The frequency of DR3/4 heterozygosity was higher in the diabetic patients (6/49 [12.2%] vs. control subjects, 0/105 [0%], P = 1.7 x 10(-3), RR = 31.5 [CI 3.8-263.6]). The frequency of DR3/9 heterozygosity also was higher in the diabetic patients (6/49 [12.2%] vs. control subjects, 2/105 [1.9%], P = 0.03, RR = 6.2 [CI 3.0-12.7]). No significant associations were noted between DQB1 alleles and IDDM. Among DR4 positive subjects, the frequency of DQB1 allele DQB1*0302 was higher in the diabetic patients (10/11 [90.0%] vs. control subjects, 12/24 [50%], Pc less than 0.05, RR = 7.0 [CI 1.3-38.0]), and the frequency of DQB1*0401 was significantly lower in the diabetic patients (2/11 [18.2%] vs. control subjects, 16/24 [66.7%], Pc = 0.04, RR = 0.1 [CI 0.02-0.46]). No DR4 subtype was associated significantly with IDDM. The frequency of DQA1*0501, a DQA1 allele, was higher in diabetic patients (22/41 [53.7%] vs. control subjects, 20/95 [21.1%], Pc less than 3 x 10( 3), RR = 4.3 [CI 2.0-9.3]). The frequency of DQA1*0301, which has been associated consistently with IDDM in other ethnic groups, was not significantly higher in the diabetic patients in this study (27/41 [65.9%] vs. control subjects, 53/95 [55.8%], NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628766 TI - Exercise training increases glucose transporter content in skeletal muscles more efficiently from aged obese rats than young lean rats. AB - Glucose uptake in rat skeletal muscles decreases with age and obesity, but increases with chronic exercise training. The purpose of our study was to determine whether the GLUT4 content in several skeletal muscles from 1-mo-old young, lean rats and 12-mo-old aged, obese rats alters with exercise training. For exercise, a treadmill run of approximately 1 km/day was made for 4 wk by both groups of rats. The concentration of GLUT4 per protein in membrane fraction from several skeletal muscles was measured by immunoblotting. The amount of GLUT4 in the gastrocnemius and white quadriceps from aged rats slightly but significantly decreased to 73% and 78% of that from young rats, respectively. However, no significant difference in GLUT4 amount in the soleus, plantaris, and red quadriceps was observed between young and aged rats. The exercise training resulted in a larger increase in the amount of GLUT4 in each muscle from aged rats than in muscles from young rats. In aged rats, GLUT4 amount increased significantly with exercise training by 30, 33, 41, and 27% in the soleus, plantaris, gastrocnemius, and red quadriceps, respectively, compared with the sedentary controls. However, in young rats, exercise-induced increase of GLUT4 amount was significant only in the plantaris, and the increase was 17%. In exercised aged, obese rats, decreases of body weight, plasma triglyceride levels, and plasma free fatty acid were also observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628767 TI - Coordinate control of lipolysis by prostaglandin E2 and prostacyclin in rat adipose tissue. AB - PGE2 is a potent antilipolytic agent produced by adipose tissue, but its role as a physiological regulator of triglyceride lipolysis is controversial because inhibitors of prostaglandin synthesis have not enhanced hormone-stimulated lipolysis in adipose tissue consistently. Adipose tissue also produces PGI2, but this eicosanoid has not had a demonstrated effect on lipolysis under physiological conditions previously. We investigated both PGE2 and PGI2 production and their effects on lipolysis in rat adipose tissue. We found that 1) EPI-stimulated PGE2 production (like PGI2 production) requires the cooperation of adipocytes and endothelial cells, 2) adipose tissue produces PGE2 and PGI2 at comparable rates, 3) indomethacin inhibits EPI-induced PGE2 and PGI2 production and has no effect on EPI-stimulated lipolysis when added to a mixture of adipocytes and endothelial cells or to intact epididymal fat pads, 4) PGI2 is a potent lipolytic agent when added to isolated adipocytes in the absence of endothelial cells under physiological conditions, 5) the magnitudes and the ED50s of the antilipolytic effect of PGE2 and the lipolytic effect of PGI2 in isolated adipocytes in the absence of endothelial cells are comparable, 6) PGI2 antagonizes the antilipolytic effect of PGE2 in isolated adipocytes in the absence of endothelial cells in a dosage-related manner, and 7) the antilipolytic effect of added PGE2 in isolated adipocytes is greater in the absence of endothelial cells than in their presence, suggesting that endogenous eicosanoid production reduces the effectiveness of added PGE2. These studies demonstrate that catecholamine-induced lipolysis is under the coordinate control of PGE2, a potent antilipolytic agent, and PGI2, a potent lipolytic agent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628768 TI - Improvement of nerve conduction in diabetic neuropathy. A follow-up study 4 yr after combined pancreatic and renal transplantation. AB - Eighteen patients with long-standing insulin-dependent (type 1) diabetes mellitus and polyneuropathy were studied after combined pancreatic and renal transplantation. Repeated tests were performed on peripheral nerve function (electroneurography) and on autonomic function (R-R test) 6 mo and 1, 2, and 4 yr after the transplantation. Eighteen diabetic patients with only a kidney graft served as controls. After initial improvement of nerve conduction in both groups, probably caused by the elimination of uremia, further improvement was seen only in the euglycemic pancreas-graft recipients. Improvement of autonomic (parasympathetic) function was slight after 48 mo and was similar in both groups. PMID- 1628769 TI - Evidence for unique distribution of Kimmelstiel-Wilson nodules in glomeruli. AB - Different distributions of segmental lesions within glomeruli correspond to different pathogenetic mechanisms. A graphic method of analysis of the position of segmental lesions was applied to 106 Kimmelstiel-Wilson nodules in 10 renal biopsies from patients with diabetic glomerulonephropathy, 4 with IDDM and 6 with NIDDM. The nodules were randomly distributed in a horseshoe-shaped area corresponding to the peripheral or intralobular mesangium. This distribution was different from that of segmental lesions studied previously in the glomerular tip lesion, in vasculitic-type glomerulonephritis, and in hyperfiltration associated with reduced renal mass. Our finding is consistent with ideas that Kimmelstiel Wilson nodules have a distinct pathogenesis not related to hyperfiltration or any other process previously investigated as a cause of characteristic distribution of segmental lesions. PMID- 1628770 TI - Somatic gene therapy for diabetes with an immunological safety system for complete removal of transplanted cells. AB - To develop somatic gene therapy for diabetes, we studied an animal model with proinsulin-producing fibroblasts with an immunological safety system. Cultured mouse fibroblasts of the Ltk- cell line were transfected first with the efficient human proinsulin expression vector pBMG-Neo-Ins. Initially, 2 x 10(6) cells with a proinsulin-production rate of 91 ng.24 h-1.10(6) cells-1 were transplanted i.p. into streptozocin-induced diabetic C3H mice. The blood glucose concentrations improved between the first and the 28th day, but the animals died of hypoglycemia between the 29th and 46th days. The proinsulin-producing Ltk- cells were further transfected with a second plasmid, pHEBo-CD8.2, encoding BALB/c mouse T-cell differentiation antigen. The CD8.2 allotype is different from CD8.1 allotype by only one amino acid substitution and should be only slightly antigenic to the recipient C3H mice. Somatic gene therapy with these doubly transfected cells followed by the consecutive administration of a monoclonal antibody to CD8.2 resulted in an initial decrease of blood glucose concentrations followed by the permanent recurrence of hyperglycemia, thus proving the complete removal of the transplanted cells. Cultured fibroblasts were thus proven capable of supplying sufficient proinsulin to lower the blood glucose concentrations in diabetic animals. The immunological safety system with a combination of artificial expression of cell surface antigen and the administration of the specific monoclonal antibody was an effective safety system for somatic gene therapy. PMID- 1628771 TI - Linkage analysis of maturity-onset diabetes of the young with microsatellite polymorphisms. No linkage to ADA or GLUT2 genes in two families. AB - MODY is a form of NIDDM inherited as an autosomal dominant condition. We studied the linkage of MODY to two loci: ADA and GLUT2 in two large pedigrees with nonradioactive microsatellite polymorphic systems. A positive linkage of ADA to MODY was recently demonstrated in the large RW pedigree. Formal linkage analysis excluded a tight linkage between ADA and MODY with a LOD score of -5.82 and -2.24 at a recombination fraction of 0.01 in the two families. This result suggests genetic heterogeneity in the molecular basis of MODY. GLUT2 is a candidate gene that is expressed in the liver and beta-cells of pancreatic islets. In the two families studied, the disease did not cosegregate with GLUT2 alleles. The LOD scores for GLUT2 were -7.79 and -1.9 at a recombination fraction of 0.001 in the two families, thus providing evidence against the involvement of GLUT2 in MODY. PMID- 1628772 TI - Ketone body metabolism in NIDDM. Effect of sulfonylurea treatment. AB - We assessed the metabolism of the two KBs, AcAc and 3-BOH; the relationships between ketogenesis and FFA inflow rate; and the effect of chronic sulfonylurea treatment in mild NIDDM patients (plasma glucose less than 10 mM). We studied 10 nonobese NIDDM patients in a crossover, randomized, double-blind, placebo controlled fashion. Each patient was studied 4 times: after a run-in period with placebo, after 3 mo of placebo treatment, after 3 mo of glibenclamide treatments, respectively, and after 3 mo of sulfonylurea treatment during an acute exogenous Intralipid infusion. Ten normal, nondiabetic subjects served as the control group. Glibenclamide treatment decreased plasma FFAs. When these substrates were exogenously increased, plasma FFAs were comparable with placebo and baseline concentrations. In NIDDM patients, baseline and placebo blood total KB concentration was significantly higher than in control subjects (216 +/- 22 and 244 +/- 25, respectively vs. 127 +/- 18 microM; P less than 0.01). Glibenclamide treatment significantly decreased total KBs to 177 +/- 19 microM (P less than 0.05). When FFAs were exogenously increased, total KBs were similar to the placebo and baseline period. In the baseline study, the AcAc/3-BOH ratio was 0.72 +/- 0.06 in control subjects, whereas in NIDDM patients, the ratio was 1.61 +/- 0.13 at baseline (P less than 0.001 vs. control subjects), 1.66 +/- 0.15 during placebo, 1.57 +/- 0.09 during glibenclamide (NS vs. baseline), and 1.51 +/- 0.23 during glibenclamide plus placebo FFAs. Both the AcAc interconversion rate to 3 BOH and the 3-BOH interconversion rate to AcAc were significantly lower in NIDDM patients than in control subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628773 TI - In vitro effects of amylin on carbohydrate metabolism in liver cells. AB - Amylin, a peptide found in pancreatic amyloid deposits, may be involved in NIDDM. The effects of biosynthetic human amylin on multiple aspects of carbohydrate metabolism were studied in freshly isolated and cultured liver cells (rat hepatocytes and HepG2 cells). Acute exposure of culture liver cells to amylin had no effect on glucose incorporation into glycogen. Amylin directly reduced glucose oxidation through the hexose monophosphate shunt. The glycolytic pathway was unaffected. Amylin stimulated both glycogenolysis and gluconeogenesis. These effects were largest at amylin concentrations of 1-10 pM. Insulin partially inhibited both of these responses. Glucagon stimulated glycogenolysis and gluconeogenesis to a similar extent as amylin but required concentrations 100- to 500-fold as high. Thus, amylin, at physiologic concentrations, can impair some aspects of glucose use in liver cells and is also capable of directly stimulating glucose production, suggesting a possible involvement of amylin in the impaired glucose disposal and elevated hepatic glucose output of NIDDM. PMID- 1628775 TI - Studies on autoimmunity for T-cell-mediated beta-cell destruction. Distinct difference in beta-cell destruction between CD4+ and CD8+ T-cell clones derived from lymphocytes infiltrating the islets of NOD mice. AB - Six CD4+ and three CD8+ islet-reactive T-cell clones were established from lymphocytes infiltrating the pancreatic islets of NOD mice. Two of six CD4+ T cell clones responded to NOD islet cells only, not to spleen cells. The remaining four clones responded to both islet cells and spleen cells from NOD mice, but not to cells from other strains of mice, including SJL, C3H, C57BL/6, and DBA/2 mice. None of the CD4+ T-cell clones had a cytotoxic effect on the cultured islet cells. On the other hand, all of the CD8+ T-cell clones showed both a proliferative response and a cytotoxic effect on the islet cells, with the restriction of MHC class I H-2Db. Electron microscopic studies revealed that islet-specific CD4+ T-cells attached closely to islet cells but did not destroy them. In contrast, CD8+ T-cell clones showed pseudopodialike protrusions into beta-cells, but not alpha- or delta-cells, leading to selective destruction of beta-cells. CD8+ CTLs could not be isolated from islets of NOD mice less than 10 wk of age, even if the islets showed lymphocytic infiltration, whereas CD4+ T cells could be isolated from islets of these younger NOD mice. On the basis of these observations, we concluded that CD4+ and CD8+ T-cells interact differently with beta-cells at different stages in T-cell--mediated beta-cell destruction. CD4+ T-cells may secrete cytokines, which in turn activate effector cell populations, whereas CD8+ T-cells may act as a final effector directly involved in beta-cell destruction. PMID- 1628774 TI - Insulinlike effects of zinc ion in vitro and in vivo. Preferential effects on desensitized adipocytes and induction of normoglycemia in streptozocin-induced rats. AB - The effects of Zn2+ in mimicking insulin in vivo and in vitro are further characterized. Like insulin, Zn2+ stimulated the conversion of [U-14C]-, [1-14C] , and [6-14C]glucose to lipids in rat adipocytes. Maximum stimulation of lipogenesis was 55-80% of maximum insulin response after preincubation (30 min at 37 degrees C) of adipocytes with ZnCl2 (0.4 mM). Under these conditions, the half maximum effect was achieved at 0.17 +/- 0.02 mM of ZnCl2. Similarly, an insulinlike effect of Zn2+ was observed on the oxidation of glucose by both pathways, glycolytic and hexose monophosphate shunt. In contrast, unlike insulin, Zn2+ did not inhibit lipolysis but rather exhibited a slight lipolytic activity. Also, the effect of Zn2+ on hexose influx did not exceed 14 +/- 3% that of insulin. The stimulatory effects of Zn2+ were not related to generation of H2O2. Catalase (100 micrograms/ml) did not inhibit Zn(2+)-stimulated glucose oxidation and its incorporation into lipids. Zn2+ had an additive effect on either insulin- or vanadate-stimulated conversion of [1-14C]glucose to fat, and together, the effect was approximately 140% of the maximum rate of lipogenesis. Chelation of intracellular Zn2+ by the cell-permeable chelator N,N,N',N'-tetrakis (2 pyridylmethyl)ethylenediamine did not significantly affect the ability of insulin to stimulate lipogenesis. Adipocytes derived from STZ rats were largely refractory to the modulating action of insulin. In contrast, the effect of Zn2+ on lipogenesis in these cells was more pronounced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628777 TI - [Coronary angioplasty in the aged: short and long term efficacy in patients with unstable angina]. AB - Coronary revascularization procedures in elderly patients are associated with an increase of perioperative complications and death in comparison with younger patients. To assess if a conservative coronary angioplasty approach is useful, 54 consecutive patients (pts) with severe unstable angina were retrospectively evaluated. Mean age was 73 years (range 70-82 years). Multivessel coronary disease was present in 26 pts (48%), angina at rest within the last 2 days in 26 (48%) and an episode of myocardial infarction within 2 weeks in 21 (38%). In 51 cases, regardless of the extension of the coronary disease, only the stenosis considered "culprit" of the symptoms, as assessed by angiography and by noninvasive studies, was dilated. The angiographic success rate was 98% (53 of 54 pts). Two pts had procedure--related myocardial infarction. One patient died after emergency bypass surgery for an abrupt left anterior descending artery occlusion. The mean hospital stay was 8 days (range 2-40 days) and in 75% cases was less than 6 days. Follow-up (achieved in 51 pts) ranged from 1 to 40 months (mean 20 months). In 3 pts a second vessel was treated with a new angioplasty 15 30 days after the first procedure due to the persistence of symptoms. During follow-up three pts died (1 death was cardiac). Of the survivors, 35 were asymptomatic in moderate medical regimen, 1 required bypass surgery and 3 were managed with repeat angioplasty. Survival was 95% at 6 months and 90% at 2 years. At six months 86% of pts were event free (80% and 70% at one and two years, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628776 TI - [A survey of cardiological emergencies in Piedmont]. AB - OBJECTIVES AND DESIGN: In order to assess the current behavioural status of patients receiving emergency cardiological treatment and the emergency services in the Piedmont Region, our Division carried out a survey of the Region's DEA and first aid centres based on the compilation of a questionnaire for each patient who passed through these structures over a 5-month period. The study included only patients hospitalised within 12 hours of symptoms' onset. The questionnaire aimed to assess the time the patient took to reach a decision, the eventual call for a home visit, the type of doctor called, the time spent by the doctor, the use of either a private vehicle or of an ambulance for transport to hospital, the time taken to get to the hospital, and the overall time taken to admit the patient to the emergency cardiological ward. The statistical analysis of data was carried out using both single and multiple variables. The selection of prognostic variables was carried out using a stepwise method. RESULTS: Data presented in this study refer to 1705 records, collected in 39 Piedmontese hospitals (75% of those with DEA or First Aid Center). Patients with acute myocardial infarction were 970 (57%). A doctor was requested at home in nearly half of the cases (49.3%). There was no correlation between the type of emergency and the request for a home visit, whereas the latter varied in relation to the different geographical areas and to the patients' age. A small majority of patients used personal transport to get to the hospital (55.5%) in comparison to those using an ambulance (44.5%) (p less than 0.001). Time taken to reach a decision was related to the type of pathology (acute pulmonary edema less than acute myocardial infarction less than arrhythmia) and to geographical area; mean decision time in the overall sample was 125 +/- 158 minutes. The mean duration of doctors' intervention at home was 74 +/- 82 minutes. The mean time taken to reach the hospital using private transport was 22 minutes, and the time taken using ambulance was the same, but this should be added to the time taken for the ambulance to reach the patient (a mean total time of 15 minutes). Overall mean hospitalisation time was 192 minutes. CONCLUSIONS: The critical factors causing delay in hospitalisation time are the poor levels of health education of the population in general, and the poor activation capacity of certain peripheral parts of the National Health Service. In particular, it is worth drawing attention to the delay due to the intervention of the family doctor in the current organisational model. Doctors called from first aid stations are able to provide a more rapid intervention, but are currently unable to meet the requirements of patients needing emergency cardiological treatments. These data confirm the rationale for intervention projects in cardiological emergencies, considering on one hand that a fleet of special vehicles be created, and on the other that doctors from first aid stations be specifically trained and increasingly involved. PMID- 1628778 TI - [Ultrasonic decalcification in aortic stenosis. Clinical and doppler echocardiographic results]. AB - Ten elderly patients with aortic valve stenosis and with a small calcified annulus (less than 20 mm) were treated by ultrasonic valve debridement (UVD) while 17 other elderly patients underwent aortic valve replacement (AVR) during the same period. The clinical and doppler results were assessed for a mean follow up period of 20 months. Patients with significant aortic regurgitation or associated valve disease were excluded. The patients were studied by m-mode, two dimensional and Doppler echocardiography before, immediately after, and at 6 months interval after the procedure. A successful decalcification was achieved in 8 patients. The valve was replaced in 2 patients because of cusp perforation or unsatisfactory intraoperative result. All patients showed significant postoperative increase in the mobility of the valve cusps, decrease in the amount of calcium, decrease of the aortic mean valve gradient (from 62 +/- 25 to 23 +/- 6 mmHg, p less than 0.001) and increase of the aortic valve area (from 0.49 +/- 0.11 to 1.21 +/- 0.3, p less than 0.001). The mean valve gradient was slightly higher after UVD than after AVR and showed a slight trend to further increase during follow-up, although only one patient had evidence of restenosis. A mild aortic valve insufficiency was present postoperatively in 6 patients. Worsening of insufficiency was noted in 2 patients during the follow-up period and one subject was re-operated on. Surgical ultrasonic debridement of the aortic valve may be effective in selected surgical candidates with small calcified valve and annulus, but subsequent occurrence of aortic insufficiency and restenosis may seriously limit its application. PMID- 1628779 TI - [Decalcification of stenotic aortic valves]. PMID- 1628780 TI - [Acute surgically-treated complications of myocardial infarct. Clinical experience and discussion of surgical indications]. AB - Post-infarction free-wall, papillary muscle and septal myocardium rupture yields a lowering mortality, not only due to the improved surgical technique but also to a more careful selection of surgical candidates. The value of pericardial decompression in cases of free-wall rupture is discussed. Echocardiographic evidence of blood in the pericardium after a myocardial infarction is not a direct indication for a diagnostic sampling, decompression or surgery. Pericardiocentesis is not a risk-free procedure and should be limited to patients with life-threatening acute tamponade. Clinical results of 34 patients operated upon for myocardial rupture, regardless of adopted technique or timing of surgery, confirm that the decision about a patient's operability should follow a careful evaluation of the following risk factors in this order: infarct size, age, cardiogenic shock, multiorgan failure, rupture site, cardiac failure and associated diseases. PMID- 1628781 TI - ["Kissing balloon" of the protected common trunk of the left coronary artery: description of a successfully treated case]. AB - The authors describe a case of coronary angioplasty on a distal Left Main coronary lesion. The left coronary tree was protected by the left internal mammary connected to left anterior descending artery. The procedure was performed using the "kissing balloon" technique, with a single guiding catheter. Immediate angiographic result and one-year follow-up have been excellent. PMID- 1628782 TI - [Post-infarction aneurysms of the left ventricle. Review of diagnostic criteria]. PMID- 1628783 TI - [Post-infarction aneurysm of the left ventricle. Physiopathology]. PMID- 1628784 TI - [Post-infarction aneurysm of the left ventricle. Natural history and prognostic stratification]. PMID- 1628785 TI - [Post-infarction aneurysm of the left ventricle. Ventricular thrombosis and embolic phenomena: the role of pharmacological therapy]. PMID- 1628786 TI - [Post-infarction aneurysms and fatal hyperkinetic ventricular arrhythmias]. PMID- 1628787 TI - [Post-infarct aneurysm of the left ventricle. Surgical treatment: indications, surgical techniques and results]. PMID- 1628788 TI - [The untransgressable geometry of the heart]. PMID- 1628789 TI - [Present-day role of hemodynamic monitoring in acute myocardial infarct]. PMID- 1628790 TI - [Efficacy and efficiency: unrenounceable objectives of the Italian cardiology]. PMID- 1628791 TI - Dental nonsteroidal anti-inflammatory drugs and prostaglandin-based drug interactions, Part one. PMID- 1628792 TI - Bulimia: dentomedical complications. PMID- 1628793 TI - Abuse of older persons: detection and prevention by dental professionals. PMID- 1628794 TI - Sonic scalers: a review. PMID- 1628795 TI - Periodontal-restorative considerations in the management of gingival palatal inflammatory hyperplasia. PMID- 1628796 TI - Unusual presentation of non-Hodgkin's lymphoma in a patient with HIV. PMID- 1628797 TI - Erupted compound odontoma: review and case report. PMID- 1628798 TI - Lingual lipoma. PMID- 1628799 TI - Immediate provisional restoration during active orthodontic therapy. PMID- 1628800 TI - The rocky road: a perspective on dental students and faculty members. PMID- 1628801 TI - Exophytic mass of the alveolar ridge. PMID- 1628802 TI - Unusual mandibular lateral incisor. PMID- 1628803 TI - Molecular genetics under an embryologist's microscope: Jean Brachet, 1909-1988. PMID- 1628804 TI - Serine and threonine catabolism in Saccharomyces cerevisiae: the CHA1 polypeptide is homologous with other serine and threonine dehydratases. AB - The catabolic L-serine (L-threonine) dehydratase of Saccharomyces cerevisiae allows the yeast to grow on media with L-serine or L-threonine as sole nitrogen source. Previously we have cloned the CHA1 gene by complementation of a mutant, cha1, lacking the dehydratase activity. Here we present the DNA sequence of a 1,766-bp fragment of the CHA1 region encompassing an open reading frame of 1080 bp. Comparison of the predicted amino acid sequence of the CHA1 polypeptide with that of other serine/threonine dehydratases revealed several blocks of sequence homology. Thus, the amino acid sequence of rat liver serine dehydratase (SDH2) and the CHA1 polypeptide are 44% homologous allowing for conservative substitutions, while 36% similarity is found between the catabolic threonine dehydratase (tdcB) of Escherichia coli and the CHA1 protein. This strongly suggests that CHA1 is the structural gene for the yeast catabolic serine (threonine) dehydratase. S1-nuclease mapping of the CHA1 mRNA ends showed a major transcription initiation site corresponding to an untranslated leader of about 19 nucleotides, while a major polyadenylation site was located about 86 nucleotides downstream from the open reading frame. Furthermore, we have mapped the chromosomal position of the CHA1 gene to less than 0.5 kb centromere proximal to HML on the left arm of chromosome III. PMID- 1628805 TI - Genes required for vacuolar acidity in Saccharomyces cerevisiae. AB - Mutations that cause loss of acidity in the vacuole (lysosome) of Saccharomyces cerevisiae were identified by screening colonies labeled with the fluorescent, pH sensitive, vacuolar labeling agent, 6-carboxyfluorescein. Thirty nine vacuolar pH (Vph-) mutants were identified. Four of these contained mutant alleles of the previously described PEP3, PEP5, PEP6 and PEP7 genes. The remaining mutants defined eight complementation groups of vph mutations. No alleles of the VAT2 or TFP1 genes (known to encode subunits of the vacuolar H(+)-ATPase) were identified in the Vph- screen. Strains bearing mutations in any of six of the VPH genes failed to grow on medium buffered at neutral pH; otherwise, none of the vph mutations caused notable growth inhibition on standard yeast media. Expression of the vacuolar protease, carboxypeptidase Y, was defective in strains bearing vph4 mutations but was apparently normal in strains bearing any of the other vph mutations. Defects in vacuolar morphology at the light microscope level were evident in all Vph- mutants. Strains that contained representative mutant alleles of the 17 previously described PEP genes were assayed for vacuolar pH; mutations in seven of the PEP genes (including PEP3, PEP5, PEP6 and PEP7) caused loss of vacuolar acidity. PMID- 1628806 TI - The structure and evolution of subtelomeric Y' repeats in Saccharomyces cerevisiae. AB - The subtelomeric Y' family of repeated DNA sequences in the yeast Saccharomyces cerevisiae is of unknown origin and function. Y's vary in copy number and location among strains. Eight Y's, from two strains, were cloned and sequenced over the same 3.2-kb interval in order to assess the within- and between-strain variation as well as address their origin and function. One entire Y' sequence was reconstructed from two clones presented here and a previously sequenced 833 bp region. It contains two large overlapping open reading frames (ORFs). The putative protein sequences have no strong homologies to any known proteins except for one region that has 27% identity with RNA helicases. RNA homologous to each ORF was detected. Comparison of the sequences revealed that the known long (Y'-L) and short (Y'-S) size classes, which coexist within cells, differ by several insertions and/or deletions within this region. The Y'-Ls from strain Y55 also differ from those of strain YP1 by several short deletions in the same region. Most of these deletions appear to have occurred between short (2-10 bp) direct repeats. The single base pair polymorphisms and the deletions are clustered in the first half of the interval compared. There is 0.30-1.13% divergence among Y' Ls within a strain and 1.15-1.75% divergence between strains in the interval. This is similar to known unique sequence variation but contrasts with the 8-18% divergence among the adjacent subtelomeric repeats, X. Subsets of Y's exhibit concerted evolution; however, more than one variant appears to be maintained within strains. The observed sequence variation disrupts the first ORF in many Y's while most of the second ORF including the putative helicase region is unaffected. The structure and distribution of the Y' elements are consistent with having originated as a mobile element. However, they now appear to move via recombination. Recombination can account for the homogenization within subsets of Y's but does not account for the maintenance of different variants. PMID- 1628807 TI - Tryptophan analog resistance mutations in Chlamydomonas reinhardtii. AB - Forty single gene mutations in Chlamydomonas reinhardtii were isolated based on resistance to the compound 5'-methyl anthranilic acid (5-MAA). In other organisms, 5-MAA is converted to 5'-methyltryptophan (5-MT) and 5-MT is a potent inhibitor of anthranilate synthase, which catalyzes the first committed step in tryptophan biosynthesis. The mutant strains fall into two phenotypic classes based on the rate of cell division in the absence of 5-MAA. Strains with class I mutations divide more slowly than wild-type cells. These 17 mutations map to seven loci, which are designated MAA1 to MAA7. Strains with class II mutations have generation times indistinguishable from wild-type cells, and 7 of these 23 mutations map to loci defined by class I mutations. The remainder of the class II mutations map to 9 other loci, which are designated MAA8-MAA16. The maa5-1 mutant strain excretes high levels of anthranilate and phenylalanine into the medium. In this strain, four enzymatic activities in the tryptophan biosynthetic pathway are increased at least twofold. These include the combined activities of anthranilate phosphoribosyl transferase, phosphoribosyl anthranilate isomerase, indoleglycerol phosphate synthetase and anthranilate synthase. The slow growth phenotypes of strains with class I mutations are not rescued by the addition of tryptophan, but the slow growth phenotype of the maa6-1 mutant strain is partially rescued by the addition of indole. The maa6-1 mutant strain excretes a fluorescent compound into the medium, and cell extracts have no combined anthranilate phosphoribosyl transferase, phosphoribosyl anthranilate isomerase and indoleglycerol phosphate synthetase activity. The MAA6 locus is likely to encode a tryptophan biosynthetic enzyme. None of the other class I mutations affected these enzyme activities. Based on the phenotypes of double mutant strains, epistatic relationships among the class I mutations have been determined. PMID- 1628808 TI - Genetic and environmental effects on the expression of peptidases and larval viability in Drosophila melanogaster. AB - The peptidase system in Drosophila melanogaster, consisting of dipeptidase-A, dipeptidase-B, dipeptidase-C and the leucine aminopeptidases, was used as a model to study the adaptive significance of enzyme activity variation. The involvement of the peptidases in osmoregulation has been suggested from the ubiquitous distribution of peptidase activities in nearly all tissues and the high concentration of amino acids and oligopeptides in the hemolymph. Under this hypothesis, larvae counteract increases in environmental osmotic stress by hydrolyzing peptides into amino acids both intra- and extracellularly to increase physiological osmotic concentration. The expression of the peptidases was studied by assaying for peptidase activities in third instar larvae of isogenic lines, which were reared under increasing levels of environmental osmotic stress using either D-mannitol or NaCl. Second and third chromosome substitution isogenic lines were used to assess the relative contribution of regulatory and structural genes in enzyme activity variation. Results indicate that: (1) genetic variation exists for peptidase activities, (2) the effect of osmotic stress is highly variable among peptidases, (3) changes in peptidase activities in response to osmotic stress depend on both genetic background and osmotic effector and (4) peptidase activities are correlated with each other, but these phenotypic correlations depend on genetic background, osmotic effector, and level of osmotic stress. Osmotic concentration in the larval hemolymph is correlated with leucine aminopeptidase activity, but changes in hemolymph osmotic concentration in response to environmental osmotic stress depend on the osmotic effector in the environment. Although these findings suggest that genetic and environmental factors contribute significantly toward the expression of enzymes with similar functions, a relative larval viability study of genotypes that differed significantly in dipeptidase-B (DIP-B) activity revealed that low DIP-B activity did not confer any measurable reduction in larval viability under increasing levels of environmental osmotic stress. These negative results suggest that, either DIP-B does not play a major role in osmoregulation or differential osmoregulation is not related to egg to adult viability in these tests. PMID- 1628809 TI - Use of a yeast site-specific recombinase to produce female germline chimeras in Drosophila. AB - We describe an efficient method for generating female germline mosaics by inducing site-specific homologous mitotic recombination with a yeast recombinase (FLP) which is driven by a heat shock promoter. These germline mosaics are produced in flies heterozygous for the agametic, germline-dependent, dominant female sterile (DFS) mutation ovoD1, where only flies possessing germline clones are able to lay eggs. This method, the "FLP-DFS" technique, is very efficient because more than 90% of females with germline clones can be recovered. We show that this heat-inducible, site-specific mitotic recombination system does not affect viability and that the germline clones recovered are physiologically the same as those created by X-ray induced mitotic recombination. We describe the parameters of FLP-recombinase induced germline mitotic recombination and the use of the "FLP-DFS" technique to analyze the maternal effect of X-linked zygotic lethal mutations. PMID- 1628810 TI - Molecular analysis of mutations induced in the vermilion gene of Drosophila melanogaster by methyl methanesulfonate. AB - The nature of DNA sequence changes induced by methyl methanesulfonate (MMS) at the vermilion locus of Drosophila melanogaster was determined after exposure of postmeiotic male germ cell stages. MMS is a carcinogen with strong preference for base nitrogen alkylation (s = 0.86). The spectrum of 40 intralocus mutations was dominated by AT----GC transitions (23%), AT----TA transversions (54%) and deletions (14%). The small deletions were preferentially found among mutants isolated in the F1 (8/18), whereas the AT----GC transitions exclusively occurred in the F2 (6/22). The MMS-induced transversions and deletions are presumably caused by N-methyl DNA adducts, which may release apurinic intermediates, known to be a time-related process. Furthermore, MMS produces multilocus deletions, i.e., at least 30% of the F1 mutants analyzed were of this type. A comparison of the mutational spectra of MMS with that produced by ethylnitrosourea (ENU), also in the vermilion locus of Drosophila, reveals major differences: predominantly transition mutations (61% GC----AT and 18% AT----GC) were found in both the F1 and F2 spectrum induced by ENU. It is concluded that the mutational spectrum of MMS is dominated by nitrogen DNA adducts, whereas with ENU DNA sequence changes mainly arose from modified oxygen in DNA. PMID- 1628811 TI - Somatic instability of a Drosophila chromosome. AB - A mitotically unstable chromosome, detectable because of mosaic expression of marker genes, was generated by X-ray mutagenesis in Drosophila. Nondisjunction of this chromosome is evident in mitotic chromosome preparations, and premature sister chromatid separation is frequent. The mosaic phenotype is modified by genetic elements that are thought to alter chromatin structure. We hypothesize that the mitotic defects result from a breakpoint deep in the pericentric heterochromatin, within or very near to the DNA sequences essential for centromere function. This unique chromosome may provide a tool for the genetic and molecular dissection of a higher eukaryotic centromere. PMID- 1628812 TI - Quantitative genetic variation in body size of mice from new mutations. AB - To measure the amount of new genetic variation in 6-week weight of mice arising each generation from mutation, selection lines derived from an initially inbred strain were maintained for 25 generations. An analysis using an animal model with restricted maximum likelihood was applied to estimate a mutational genetic component of variance for the infinitesimal model of many genes of small effect. Assuming that the inbred base population was at a mutation-drift equilibrium, it is estimated that the heritability for body size has increased by 1.0% per generation, with lower and upper confidence limits of 0.6% and 1.6%, respectively. A model which includes a mutational genetic component of variance fits the data much better than one involving only base population genetic variance. A model with no genetic component fits the data very poorly. An environmental covariance of body size of mother and offspring was included in the model and accounts for 10% of the variance. By using information only from the observed response to selection, the estimated increase in heritability from mutation is 0.3% per generation. These values are higher than published estimates for the increase in variance from spontaneous mutations in bristle traits of Drosophila, for which there are extensive data, but similar to estimates for various skeletal traits in mice. PMID- 1628813 TI - Rat gene mapping using PCR-analyzed microsatellites. AB - One hundred and seventy-four rat loci which contain short tandem repeat sequences were extracted from the GenBank or EMBL data bases and used to define primers for amplification by the polymerase chain reaction (PCR) of the microsatellite regions, creating PCR-formatted sequence-tagged microsatellite sites (STMSs). One hundred and thirty-four STMSs for 118 loci, including 6 randomly cloned STMSs, were characterized: (i) PCR-analyzed loci were assigned to specific chromosomes using a panel of rat x mouse somatic cell hybrid clones. (ii) Length variation of the STMSs among 8 inbred rat strains could be visualized at 85 of 107 loci examined (79.4%). (iii) A genetic map, integrating biochemical, coat color, mutant and restriction fragment length polymorphism loci, was constructed based on the segregation of 125 polymorphic markers in seven rat backcrosses and in two F2 crosses. Twenty four linkage groups were identified, all of which were assigned to a defined chromosome. As a reflection of the bias for coding sequences in the public data bases, the STMSs described herein are often associated with genes. Hence, the genetic map we report coincides with a gene map. The corresponding map locations of the homologous mouse and human genes are also listed for comparative mapping purposes. PMID- 1628814 TI - Deleterious mutations and the origin of the meiotic ploidy cycle. AB - A population genetical model is investigated in which the organism either alternates between diploid and haploid states or lives entirely in the haploid state. The behavior of the organism is determined by the genotype at a modifier locus. At an independent locus deleterious mutations occur at a low but constant frequency. It is found that the haploid behavior is always an evolutionarily attainable stable trait, while the ploidy-cyclic behavior is an evolutionarily attainable stable trait only when a certain condition holds. This condition depends on the strength of selection, the degree of "sheltering" given by the heterozygote state, and the degree of linkage between the modifier locus and the locus under selection. The last result leads to the speculation that the eukaryotes are derived from an organism which first developed more than one chromosome before it evolved the ploidy cycle. PMID- 1628815 TI - Recombination and the evolution of diploidy. AB - With two copies of every gene, a diploid organism is able to mask recessive deleterious mutations. In this paper we present the analysis of a two-locus model designed to determine when the masking of deleterious alleles favors the evolution of a dominant diploid phase in organisms that alternate between haploid and diploid phases ("alternation of generations"). It is hypothesized that diploidy will be favored whenever masking occurs ("the masking hypothesis"). Using analytical methods, we confirm that this masking hypothesis is essentially correct under free recombination: as long as the heterozygous expression of deleterious alleles is sufficiently masked by the wild-type allele, diploidy is favored over haploidy. When the rate of recombination is lower, however, diploidy is much less likely to be favored over haploidy. In fact, according to our model, the evolution of diploidy is impossible without significant levels of recombination even when masking is fairly strong. PMID- 1628816 TI - Inference of horizontal genetic transfer from molecular data: an approach using the bootstrap. AB - Inconsistencies in taxonomic relationships implicit in different sets of nucleic acid sequences potentially result from horizontal transfer of genetic material between genomes. A nonparametric method is proposed to determine whether such inconsistencies are statistically significant. A similarity coefficient is calculated from ranked pairwise identities and evaluated against a distribution of similarity coefficients generated from resampled data. Subsequent analyses of partial data sets, obtained by the elimination of individual taxa, identify particular taxa to which the significance may be attributed, and can sometimes help in distinguishing horizontal genetic transfer from inconsistencies due to convergent evolution or variation in evolutionary rate. The method was successfully applied to data sets that were not found to be significantly different with existing methods that use comparisons of phylogenetic trees. The new statistical framework is also applicable to the inference of horizontal transfer from restriction fragment length polymorphism distributions and protein sequences. PMID- 1628817 TI - Induction of recessive lethal and specific locus mutations in the zebrafish with ethyl nitrosourea. AB - Recessive lethal mutations and mutations at the gol-1 locus were induced in the zebrafish by exposure of mature sperm to the alkylating agent ethyl nitrosourea (ENU). Embryonic lethal phenotypes were recognized among the parthenogenetic progeny of mutagenized animals or among the progeny of daughters of mutagenized animals. Novel specific locus mutations were identified by the failure of mutagenized chromosomes to complement pre-existing mutant alleles at the gol-1 locus. Each mutagenized individual harboured approximately 10 embryonic lethal mutations in its germ line and about 1 in 500 mutagenized animals harboured a new mutation at the gol-1 locus. Three lines of evidence indicate that the majority of mutations that were recovered following treatment of mature sperm with ENU were probably point mutations. First, the soma and germ lines of mutagenized animals were mosaic, as expected following simple alkylation of sperm DNA. Second, mutations induced by ENU at the gol-1 locus affected pigmentation but not viability, unlike the majority of mutations induced at this locus with gamma irradiation. Third, the ratio of specific locus:recessive lethal mutations induced by ENU was approximately 50-fold lower than the ratio observed following mutagenesis with gamma-rays. Comparison of the incidence with which embryonic recessive lethal mutations were induced with the incidence with which specific locus mutations arose indicates that there are greater than 5000 genes essential to the development and viability of the zebrafish embryo. PMID- 1628818 TI - Estimating effective population size from samples of sequences: inefficiency of pairwise and segregating sites as compared to phylogenetic estimates. AB - It is known that under neutral mutation at a known mutation rate a sample of nucleotide sequences, within which there is assumed to be no recombination, allows estimation of the effective size of an isolated population. This paper investigates the case of very long sequences, where each pair of sequences allows a precise estimate of the divergence time of those two gene copies. The average divergence time of all pairs of copies estimates twice the effective population number and an estimate can also be derived from the number of segregating sites. One can alternatively estimate the genealogy of the copies. This paper shows how a maximum likelihood estimate of the effective population number can be derived from such a genealogical tree. The pairwise and the segregating sites estimates are shown to be much less efficient than this maximum likelihood estimate, and this is verified by computer simulation. The result implies that there is much to gain by explicitly taking the tree structure of these genealogies into account. PMID- 1628819 TI - Mapping and characterization of a 'speciation gene' in Drosophila. AB - Almost nothing is known about the identity of the genes causing reproductive isolation between species. As a first step towards molecular isolation of a 'speciation gene', I mapped and partly characterized a gene causing hybrid male sterility in Drosophila. This analysis shows that sterility of D. melanogaster males who carry the 'dot' fourth chromosome from D. simulans is due entirely to a very small region of the D. simulans chromosome (including only about 5 salivary gland bands or approximately 250 kb of DNA). Thus the hybrid sterility effect of the D. simulans fourth chromosome is almost surely due to a single gene of very large effect (here named hms, hybrid male sterile). Hms is zygotically acting, and the D. simulans allele of hms is completely recessive. Furthermore, complementation tests suggest that hms is not an allele of any known locus in D. melanogaster. PMID- 1628820 TI - Further observation of paternal transmission of Drosophila mitochondrial DNA by PCR selective amplification method. AB - By designing 3' ends of primers in PCR (polymerase chain reaction), a specific DNA fragment was selectively amplified in the presence of a 10(3)-fold excess of highly homologous (sequence difference ca. 2%) opponent DNA. This technique was applied in detecting paternal leakage of mitochondrial DNA (mtDNA) in intraspecific crosses of Drosophila simulans and interspecific crosses of Drosophila simulans and Drosophila mauritiana. The mtDNA types of their progeny were analysed by selective amplification of the paternal mtDNA fragment possessing a polymorphic restriction site and detecting its cleaved fragments. Paternal mtDNA was detected in the progeny of 14 out of 16 crosses. The present result indicates small but frequent inheritance of sperm mtDNA in Drosophila, which is supportive to our previous finding. PMID- 1628821 TI - Induction of mutations in the zebrafish with ultraviolet light. AB - Recessive lethal germline and specific locus somatic mutations were induced efficiently in the zebrafish by exposure of mature sperm to UV light. Mutagenesis of sperm yielded mosaic individuals: clones bearing novel mutations represented approximately 12-25% of the haploid germ cells and 25-50% of the somatic tissue. Simple methods are described for the reliable identification and propagation of newly arising developmental mutations in zebrafish. PMID- 1628822 TI - Wild-type p53 mediates positive regulation of gene expression through a specific DNA sequence element. AB - It has been reported recently that the wild-type p53 gene product can positively regulate the expression of a test gene adjacent to the enhancer-promoter elements of the murine muscle-specific creatine kinase (MCK) gene. This discussion reports the identification of a wild-type p53 protein-specific DNA-binding element located within the p53-responsive region of the MCK enhancer-promoter element. This p53 protein/DNA-binding element has been defined by DNase I footprint analysis, which identified a 50-bp region. This 50-bp sequence was sufficient to confer wild-type p53 responsiveness on a heterologous minimal promoter. The mutant forms of p53 protein are much less capable of stimulating this DNA element. This study has identified the first example of a naturally occurring wild-type p53-specific DNA-binding element that is able to mediate positive regulation of a test gene. The results suggest a biological function in gene regulation for the wild-type p53 protein that is lost or altered in the mutant p53 proteins. PMID- 1628823 TI - The human heat shock protein hsp70 interacts with HSF, the transcription factor that regulates heat shock gene expression. AB - Transcriptional regulation of the human hsp70 gene in response to heat shock and other forms of physiological stress occurs through the activation of heat shock transcription factor (HSF). Exposure of cells to a heat shock temperature of 42 degrees C results in transient activation of HSF; its DNA-binding activity increases rapidly, plateaus, and attenuates, during which the intracellular levels of hsp70 increase. In an effort to understand whether HSF is regulated negatively by hsp70, we have examined whether HSF associates with hsp70. We show that activated HSF associates with hsp70 and that the interaction is detected as the levels of hsp70 increase in the cell. Addition of ATP and other hydrolyzable nucleotides results in the dissociation of hsp70 from HSF while nonhydrolyzable nucleotide analogs do not disrupt the complex. We demonstrate that exogenous recombinant wild-type hsp70 can associate with activated HSF, whereas no association is observed with an amino-terminal or a carboxy-terminal deletion mutant of hsp70. We also show that hsp70 blocks the in vitro activation of HSF from its cryptic non-DNA-binding state to a DNA-binding form; this inhibitory effect of hsp70 is abolished by ATP. We suggest that hsp70 may negatively regulate the activation of HSF. PMID- 1628824 TI - DnaK and DnaJ heat shock proteins participate in protein export in Escherichia coli. AB - In Escherichia coli secreted proteins must be maintained in an export-competent state before translocation across the cytoplasmic membrane. This function is carried out by a group of proteins called chaperones. SecB is the major chaperone that interacts with precursor proteins before their secretion. We report results indicating that the DnaK and DnaJ heat shock proteins are also involved in the export of several proteins, most likely by acting as their chaperones. Translocation of alkaline phosphatase, a SecB-independent protein, was inhibited in dnaK- and dnaJ- mutant strains, suggesting that export of this protein probably involves DnaK and DnaJ. In addition, DnaK and DnaJ play a critical role in strains lacking SecB. They are required both for viability and for the residual processing of the SecB-dependent proteins LamB and maltose-binding protein (MBP) seen in secB null strains. Furthermore, overproduction of DnaK and DnaJ permits strains lacking SecB to grow in rich medium and accelerates the processing of LamB and MBP. These results suggest that under conditions where SecB becomes limiting, DnaK and DnaJ probably substitute for SecB and facilitate protein export. This provides the cell with a mechanism to overcome a temporary imbalance in the secretion process caused by an abrupt expansion in the pool of precursor proteins. PMID- 1628826 TI - Gene expression during preimplantation mouse development. AB - To develop a resource for the identification and isolation of genes expressed in the early mammalian embryo, large and representative cDNA libraries were constructed from unfertilized eggs, and two-cell, eight-cell, and blastocyst stage mouse embryos. Using these libraries, we now report the first stages at which the cytokines interleukin (IL)-6, IL-1 beta, and interferon (IFN)-gamma are transcribed in the developing embryo and the presence of IL-7 transcripts in the unfertilized egg. Transcripts for IL-1 alpha, -2, -3, -4, or -5 were not detected at these stages. To identify novel genes expressed on activation of the embryonic genome, the egg and eight-cell stage-specific cDNA libraries were subtracted from the two-cell library, yielding a specialized cDNA library enriched for transcripts expressed at the two-cell stage. Sequence and Southern blot analysis of several of these cDNAs expressed predominantly at the two-cell stage of embryogenesis revealed them to be from novel genes, thereby providing the first molecular tools with which to approach the study of gene expression in the early mammalian embryo. PMID- 1628825 TI - Isolation and characterization of RAT1: an essential gene of Saccharomyces cerevisiae required for the efficient nucleocytoplasmic trafficking of mRNA. AB - We have combined techniques of genetics and histochemistry to identify genes required for the nucleocytoplasmic export of mRNA in the budding yeast Saccharomyces cerevisiae. We adapted in situ hybridization using a digoxigenin labeled oligo(dT)50 probe to localize poly(A)+ RNA in fixed yeast cells and used yeast strains carrying the rna1-1 mutation to develop an assay. The rna1-1 mutation is the only previously described mutation that causes defects in mRNA export. As visualized with this RNA localization assay, rna1-1 strains accumulated poly(A)+ RNA at the nuclear periphery at the nonpermissive temperature. This was in contrast to the RNA localization pattern of wild-type cells or rna1-1 cells grown at permissive temperature. Wild-type cells showed bright uniform cytoplasmic staining with little detectable RNA in the nuclei. We used this RNA localization assay to screen a bank of temperature-sensitive yeast strains for mutants with inducible defects in mRNA trafficking. Strains identified in this manner are designated RAT mutants for ribonucleic acid trafficking. The rat1-1 allele conferred temperature-sensitive accumulation of poly(A)+ RNA in one to several intranuclear spots that appear to lie at the nuclear periphery. RNA processing was unaffected in rat1-1 strains, except for an inducible defect in trimming the 5' end of the 5.8S rRNA. The wild-type RAT1 gene was cloned by complementation; it encodes an essential 116-kD protein with regions of homology to the protein encoded by SEP1 (also known as DST2, XRN1, KEM1, and RAR5). Sep1p is a nucleic acid binding protein, a 5'----3' exonuclease, and catalyzes DNA strand transfer reactions in vitro. We discuss the possible significance of the Rat1p/Sep1p homology for RNA trafficking. We also discuss the potential of this RNA localization assay to identify genes involved in nuclear structure and RNA metabolism. PMID- 1628827 TI - Isolation of novel murine maternal mRNAs regulated by cytoplasmic polyadenylation. AB - The cytoplasmic polyadenylation element (CPE) is an AU-rich sequence in the 3' untranslated region of many stored maternal mRNAs. The CPE directs the meiotic maturation-specific cytoplasmic polyadenylation and translational activation of these dormant mRNAs in Xenopus. The work presented here demonstrates that the CPE controls a similar regulation in mouse oocytes and utilizes the information to isolate novel maternal mRNAs by polymerase chain reaction (PCR). A degenerate CPE primer was used in an anchored PCR reaction with cDNAs from primary mouse oocytes. Clones were identified that contained the canonical polyadenylation signal AATAAA. A novel PCR test was then used to determine the polyadenylation state of the respective mRNAs before and after meiotic maturation. Two mRNAs, OM 1 and OM-2, are cytoplasmically polyadenylated upon maturation. Another mRNA is not polyadenylated during maturation, although it contains multiple CPE-like elements, indicating that this sequence element is not sufficient for adenylation during this time. Microinjection into primary oocytes of antisense oligodeoxynucleotides directed against OM-1 destroys the mRNA but does not appear to interfere with maturation in vitro. These experiments identify two novel maternal mRNAs and establish a simple strategy for isolating other maternal messages that control meiotic maturation, fertilization, and early mouse development. PMID- 1628828 TI - Replication of distinct scrapie prion isolates is region specific in brains of transgenic mice and hamsters. AB - Scrapie prions are composed largely, if not entirely, of PrPSc molecules. The prion isolates Sc237 and 139H exhibit markedly different incubation times in Syrian, Armenian, and Chinese hamsters, as well as in transgenic (Tg) 81 mice expressing Syrian hamster PrP (SHaPrP). Repassage of prions from transgenic mice or Chinese hamsters into Syrian hamsters revealed that the original properties of the prion isolates are retained. When Syrian hamsters were first inoculated with 139H prions and subsequently challenged with Sc237 prions, the incubation period was determined by the faster Sc237 isolate. Regional mapping studies demonstrated different kinetics and patterns of PrPSc accumulation for Sc237 and 139H prions in the brains of Syrian hamsters as well as Tg(SHaPrP)7 mice. That distinct prion isolates induce different region-specific accumulations of PrPSc in brain suggests a novel mechanism for propagation of isolates whereby they replicate in particular sets of neurons. The prion isolates could be targeted to specific CNS cells by differing conformations of PrPSc, post-translational modifications of PrPSc such as Asn-linked glycosylation, or an as yet undetected macromolecule complexed with PrPSc in the prion. PMID- 1628829 TI - Translational activation of the non-AUG-initiated c-myc 1 protein at high cell densities due to methionine deprivation. AB - c-myc belongs to a small, yet growing, group of eukaryotic mRNAs that initiate translation inefficiently from a non-AUG codon upstream from a more efficient AUG codon. We have examined the translational regulation of non-AUG-initiated c-myc 1 and AUG-initiated c-myc 2 protein synthesis in avian and mouse cells during proliferation. As lymphoid, erythroid, and embryo fibroblast cells approached high densities in culture, there was a sustained 5- to 10-fold induction in the synthesis of c-myc 1 protein to levels greater than or equal to c-myc 2 protein synthesis. Treatment with conditioned/depleted media from high-density cells was able to reproduce this activation in low-density cells within 5 hr. Additional studies with the conditioned/depleted media revealed that amino acid availability, specifically methionine deprivation, was responsible for this unique translational control. Our results describe a specific and dramatic regulation of dual translational initiation. Furthermore, these results represent a novel translational activation of a specific gene in higher eukaryotes in response to nutrient deprivation. PMID- 1628830 TI - Analysis of the functional role of the Polycomb chromo domain in Drosophila melanogaster. AB - The chromo domain was identified as a homologous protein motif between Polycomb (Pc)--a member of the Pc-group genes encoding transcriptional repressors of the homeotic genes--and HP1--a heterochromatin-associated protein encoded by the suppressor of position effect variegation gene Su(var)205. Together with previous genetic studies, this molecular similarity supports the suggestion of a common mechanism used for generating heterochromatin and for repressing homeotic genes. The evolutionary conservation of the chromo domain throughout the animal and plant kingdoms implies an important functional role for this protein motif. We have used transgenic lines as well as transient expression assays employing Drosophila tissue culture cells to study the functional role of the Pc chromo domain. Wild-type Pc protein is endogenously expressed in SL2 cells and is found in large immunologically visible complexes. Mutated Pc proteins were expressed as Pc-beta-galactosidase fusion proteins, and their nuclear distribution was examined by indirect immunofluorescence in tissue culture cells and on polytene chromosomes of transgenic larvae. We show that carboxy-terminal truncations of the Pc protein do not affect chromosomal binding of the fusion protein. However, mutations affecting only the chromo domain including in vitro generated deletions, as well as point mutations, abolish chromosomal binding. Our results demonstrate for the first time that the chromo domain is important for the function of Pc and that it is absolutely required for binding of Pc protein to chromatin. Some of the nuclear patterns generated by the mutated forms of the fusion proteins suggest, furthermore, that the chromo domain could be involved in a packaging mechanism, essential for compacting chromosomal proteins within heterochromatin or heterochromatin-like complexes. PMID- 1628831 TI - Signal transduction in Saccharomyces cerevisiae requires tyrosine and threonine phosphorylation of FUS3 and KSS1. AB - The FUS3 and KSS1 kinases are components of the pheromone-dependent signal transduction pathway in yeast. We show that FUS3 and KSS1 become rapidly phosphorylated after pheromone treatment. Similar to mammalian MAP kinases, this modification occurs at two amino acids of FUS3, threonine-180 and tyrosine-182. A mutation introduced at either position results in complete loss of function in vivo. Amino acid substitutions that destroy catalytic activity of the kinase do not prevent phosphorylation of the mutant products, a result that excludes an autocatalytic activation pathway. The modification of FUS3 is dependent on kinases encoded by the STE11 and STE7 genes. Furthermore, a hyperactive allele of STE11 causes increased phosphorylation of FUS3 in the absence of pheromone stimulation. Thus, either STE7 or STE11 could be the kinase responsible for the phosphorylation of FUS3. PMID- 1628832 TI - Constitutive mutants of the protein kinase STE11 activate the yeast pheromone response pathway in the absence of the G protein. AB - STE4 encodes the beta-subunit of a heterotrimeric guanine nucleotide-binding protein (G protein) that is an early and essential component of the pheromone signal transduction pathway. From a ste4 deletion strain we have isolated both dominant and recessive suppressors that show increased transcription of pheromone responsive genes and have regained the ability to mate, albeit at a low level. Each of these suppressor mutations suppresses ste4 and ste5 deletions but not deletions in STE7, STE11, or STE12. Among the dominant mutations, we have identified two alleles of STE11, a gene that encodes a protein kinase activity essential for mating. One allele contains an alteration in the putative regulatory domain of the protein kinase; the second allele has an alteration in the catalytic site. In strains carrying these mutations, a second protein kinase required for mating, STE7, becomes hyperphosphorylated, just as it does in wild type cells treated with pheromone. Thus, a protein kinase cascade appears to be an essential feature of the response pathway and probably connects the receptor/G protein to an identified transcription factor, STE12. PMID- 1628833 TI - Order of action of components in the yeast pheromone response pathway revealed with a dominant allele of the STE11 kinase and the multiple phosphorylation of the STE7 kinase. AB - The signal transduction pathway that mediates the response of haploid yeast cells to peptide mating pheromones involves several components including the protein kinases STE7 and STE11. We have isolated and characterized a dominant allele of the STE11 gene and have demonstrated that expression of an amino-terminally truncated form of STE11 protein causes constitutive activation of the mating pathway. Expression of this dominant STE11 allele also restored mating ability to certain sterile strains. In conjunction with the results of others, our epistasis results establish the following order of action of pathway components: STE2, GPA1(SCG1), STE4, STE5, STE11, STE7, STE12. Transduction of the signal from STE11 to STE7 may involve phosphorylation because STE7 displays several phosphorylation forms, and STE7 is multiply phosphorylated in response to either pheromone or coexpression of dominant STE11 protein. Further signal propagation appears to require STE7 protein kinase activity, because a catalytically impaired STE7 mutant is defective in the mating response. PMID- 1628834 TI - SPT3 interacts with TFIID to allow normal transcription in Saccharomyces cerevisiae. AB - Mutations in the Saccharomyces cerevisiae gene SPT15, which encodes the TATA binding protein TFIID, have been shown to cause pleiotropic phenotypes and to lead to changes in transcription in vivo. Here, we report the cloning and analysis of one such mutation, spt15-21, which causes a single-amino-acid substitution in a conserved residue of TFIID. Surprisingly, the spt15-21 mutation does not affect the stability of TFIID, its ability to bind to DNA or to support basal transcription in vitro, or the ability of an upstream activator to function in vivo. To study further the spt15-21 defect, extragenic suppressors of this mutation were isolated and analyzed. All of the extragenic suppressors of spt15 21 are mutations in the previously identified SPT3 gene. Suppression of spt15-21 by these spt3 mutations is allele-specific, suggesting that TFIID and SPT3 interact and that spt15-21 impairs this interaction in some way. Consistent with these genetic data, coimmunoprecipitation experiments demonstrate that the TFIID and SPT3 proteins are physically associated in yeast extracts. Taken together, these results suggest that SPT3 is a TFIID-associated protein, required for TFIID to function at particular promoters in vivo. PMID- 1628835 TI - Acetylornithine deacetylase, succinyldiaminopimelate desuccinylase and carboxypeptidase G2 are evolutionarily related. AB - The nucleotide (nt) sequence of the Escherichia coli argE gene, encoding the acetylornithine deacetylase (AO) subunit, has been established and corresponds to a 43-kDa (M(r) 42,320) polypeptide. The enzyme has been purified to near homogeneity and it appears to be a dimer consisting of two 43-kDa subunits. The amino acid sequence deduced from the nt sequence was compared to that of the subunit of E. coli succinyldiaminopimelate desuccinylase (the dapE gene product involved in the diaminopimelate pathway for lysine biosynthesis), since both enzymes share functional and biochemical features. Significant similarity covering the entire sequence allows us to infer a common origin for both deacylases. This homology extends to the Pseudomonas sp. G2 carboxypeptidase (G2CP); this or a functionally related enzyme may be responsible for the minor AO activity found in organisms relying on ornithine acetyltransferase for ornithine biosynthesis. PMID- 1628836 TI - Cloning and sequence analysis of a Candida maltosa gene which confers resistance to cycloheximide. AB - A CYHR gene from Candida maltosa, which confers resistance to cycloheximide, was cloned in Saccharomyces cerevisiae. A 2.3-kb DNA fragment carrying this gene was sequenced, and an open reading frame able to encode 553 amino acids (aa) was found in the sequence. Computer searches of the GenBank, EMBL, SWIS-PROT and Gen Pept databases using the FASTA program failed to detect any proteins with extensive similarities to the deduced aa sequence for CYHR. The cloned gene transforms S. cerevisiae at a frequency similar to auxotrophic markers and can be used as a dominant selectable marker for introducing recombinant plasmids into wild-type strains of S. cerevisiae, as well as for gene disruption experiments. PMID- 1628837 TI - Secretion of a Cryptococcus albidus xylanase in Saccharomyces cerevisiae. AB - The xylanase(XLN)-encoding gene(XLN) of Cryptococcus albidus and its cDNA were each inserted into the vector, pVT100, for expression in Saccharomyces cerevisiae. Expression was under the control of either their own promoter or the gene encoding alcohol dehydrogenase (ADH1) promoter. Yeast transformed with plasmids containing the cDNA of the structural XLN gene and the XLN promoter produced active extracellular XLN when grown with galactose as carbon source. However, with glucose as carbon source, XLN was repressed. Using the ADH1 promoter, which is stimulated by glucose, XLN was secreted into the culture medium. In both cases, the secreted 48-kDa enzyme corresponded to the native XLN produced by C. albidus. With the plasmid bearing the genomic XLN gene, there was transcription, but the seven introns interrupting XLN were not spliced out by S. cerevisiae and no enzyme was produced. PMID- 1628838 TI - Ligation-free gene synthesis by PCR: synthesis and mutagenesis at multiple loci of a chimeric gene encoding ompA signal peptide and hirudin. PMID- 1628839 TI - A fusion plasmid for the synthesis of lipopeptide-antigen chimeras in Escherichia coli. AB - Lipopeptides are potential vaccine candidates with a built-in adjuvant property. To circumvent the present chemical route of synthesis for lipopeptide-antigen conjugates, the lipoprotein property of the pColE2-P9-encoded lysis protein, CelB, was used to create the bacterial fusion plasmid, pKLY3, to produce lipopeptide-antigen chimeras in Escherichia coli. Plasmid pKLY3 is a derivative of pKK233-2 with the origin of replication of the single-stranded DNA phage, fl. Under control of the promoter, ptrc, is the 5' end of the celB gene coding for a lipoprotein signal peptide and the first five amino acids (aa) (CQANY) of the mature lysis protein. As model systems for the synthesis of small and large lipopeptide-antigens, DNA sequences coding for the P2 peptide and E. coli alkaline phosphatase (PhoA) were fused in frame to the region of celB coding for a lipoprotein signal peptide and CQANY. P2 is a 12-aa peptide including a tyrosine phosphorylation site of the epidermal growth factor receptor (EGF-R). Inducible expression of stable lipohexapeptide CQANYV, lipo-CQANY-P2, and lipo CQANYA-PhoA, was demonstrated. Similar expression was obtained for lipo-CIEGR-P2 and lipo-CIEGRA-PhoA in which IEGR is a cleavage recognition site for the blood coagulation factor, Xa. Like QANY, IEGR is predicted to form a beta-turn structure. The presence of a lipid moiety on the products was confirmed by demonstrating the incorporation of radioactive palmitic acid and inhibition of processing by globomycin. The lipid-modified peptides were also identified by incorporation of radioactive tyrosine, and the nature of the P2 peptide was verified immunologically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1628840 TI - 'Stop-codon-specific' restriction endonucleases: their use in mapping and gene manipulation. AB - Certain restriction endonucleases recognise target sequences that contain the stop triplet TAG and are commonly either 4 or 6 bp in length. Interestingly, these restriction targets do not occur at the frequency expected on the basis of base composition and size. For example, the tetranucleotide MaeI recognition sequence (CTAG) occurs considerably less commonly (5-8-fold) in the genome of Escherichia coli (and many other eubacteria) than expected from mononucleotide frequencies. This surprising rarity is particularly evident in protein-encoding genes and is largely dictated by codon usage. Thus, amber (TAG) nonsense mutations frequently give rise to novel MaeI (CTAG) sites which are unique within a translated region. Such amber/MaeI sites, whether arising spontaneously or created in vitro by site-directed mutagenesis, act as a useful physical marker for the presence of the nonsense mutation and are a convenient startpoint for a range of diverse procedures. These features provide a useful supplement to protein engineering methods which use nonsense suppression to mediate amino acid replacements. PMID- 1628841 TI - Expression of the Erwinia carotovora polygalacturonase-encoding gene in Bacillus subtilis: role of signal peptide fusions on production of a heterologous protein. AB - The pehA gene encoding an endopolygalacturonase (pectinase) of Erwinia carotovora subsp. carotovora has been cloned previously [Saarilahti et al., Mol. Microbiol. 4 (1990) 1037-1044]. We expressed pehA in Bacillus subtilis using a secretion vector based on the promoter and signal sequence of the alpha-amylase (Amy) encoding gene, amyE, from Bacillus amyloliquefaciens. To test whether the location of the junction between the secretion vector and pehA affects the protein yield, we made four different junctions. Two constructs contained an intact Amy signal sequence, whereas the other two were fusions between the Amy signal sequence and the polygalacturonase (PG) signal sequence. There was approximately fourfold variation in the production efficiency of B. subtilis strains carrying the different constructs. The most efficient construct contained the N-terminal and hydrophobic regions of the Amy signal peptide joined to the C terminus of PG signal peptide. This construct produced, in a shake flask culture, 0.8 g of polygalacturonase per liter of growth medium. In a pulse-chase experiment, the signal peptide of the most efficient construct was rapidly cleaved while cleavage was slow in the other constructs. Our results suggest that fusions containing intact signal peptides, which are common when producing foreign proteins, are not necessarily the most efficient. PMID- 1628842 TI - In vivo inactivation of the Streptococcus mutans recA gene mediated by PCR amplification and cloning of a recA DNA fragment. AB - The inactivation of the RecA protein in pathogenic oral streptococci would facilitate genetic analysis of potential virulence factors in these strains. Comparison of recA nucleotide (nt) sequences from a number of bacteria has suggested that two regions of highly conserved RecA amino acid (aa) sequence could be used as a basis for synthesizing degenerate oligodeoxyribonucleotide primers with which to amplify recA homologues from the streptococci. Accordingly, primer mixtures were used to amplify a 693-bp fragment of the Streptococcus mutans chromosome by PCR. The amplified fragment was cloned and its identity confirmed via hybridization to an Escherichia coli recA gene probe and by nt sequence determination. The recA homologue fragment from S. mutans GS-5 was 63% and 75% homologous to the deduced aa sequences of the E. coli and Bacillus subtilis RecA enzymes, respectively. The S. mutans recA fragment was mutagenized in vitro via insertional inactivation and returned to the chromosome using allelic exchange. The resulting strains of S. mutans were shown to be substantially more sensitive to UV irradiation than the wild-type strain. Further, the ability to incorporate linear markers into the chromosome was abolished in putative S. mutans recA strains, thus indicating the functional inactivation of RecA in these microorganisms. PMID- 1628843 TI - Plasmid cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp. AB - We have constructed cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp. All vectors contain the 760-bp oriT fragment from the IncP plasmid, RK2. Transfer functions need to be supplied in trans by the E. coli donor strain. We have incorporated into these vectors selectable antibiotic-resistance markers (AmR, ThR, SpR) that function in Streptomyces spp. and other features that should allow for: (i) integration via homologous recombination between cloned DNA and the Streptomyces spp. chromosome, (ii) autonomous replication, or (iii) site-specific integration at the bacteriophage phi C31 attachment site. Shuttle cosmids for constructing genomic libraries and bacteriophage P1 cloning vector capable of accepting approx. 100-kb fragments are also described. A simple mating procedure has been developed for the conjugal transfer of these vectors from E. coli to Streptomyces spp. that involves plating of the donor strain and either germinated spores or mycelial fragments of the recipient strain. We have shown that several of these vectors can be introduced into Streptomyces fradiae, a strain that is notoriously difficult to transform by PEG-mediated protoplast transformation. PMID- 1628844 TI - Isolation, characterization, and sequencing of Candida albicans repetitive element 2. AB - A 1059-bp Sau3A fragment, designated Candida albicans repetitive element 2 (CARE 2), was isolated from the genome of the pathogenic yeast, C. albicans. CARE-2 DNA was detected on several C. albicans chromosomes separated by transverse alternating-field electrophoresis. A high degree of interstrain variation in the pattern of hybridizing bands were observed by Southern blot analysis, with a minimum of 10-14 copies of CARE-2 per strain. A low frequency of new CARE-2 polymorphisms was observed over time for three strains grown at 25 degrees C or 37 degrees C. No new CARE-2 polymorphisms were observed from two naturally occurring switch phenotypes. To localize repeated DNA, oligodeoxyribonucleotide probes, each representing a different region of CARE-2, were hybridized to genomic blots. A lower number of copies were observed 5' and 3' to a 600-bp region of CARE-2. Nucleotide (nt) sequence analysis of CARE-2 DNA shows the element is characterized by six perfect direct repeats 6 bp in length and shows no significant DNA similarity with any known nt sequence. PMID- 1628845 TI - Cloning and sequence analysis of the Mucor circinelloides pyrG gene encoding orotidine-5'-monophosphate decarboxylase: use of pyrG for homologous transformation. AB - A 3.2-kb BamHI genomic DNA fragment containing the pyrG gene of Mucor circinelloides was isolated by heterologous hybridization using a pyrG cDNA clone of Phycomyces blakesleeanus as the probe. The complete nucleotide sequence of the M. circinelloides pyrG gene encoding orotidine-5'-monophosphate decarboxylase (OMPD) was determined and the transcription start points (tsp) were mapped by primer extension analysis. The predicted amino acid sequence showed homology with the OMPD sequences reported from other filamentous fungi, with 96% similarity with the OMPD of P. blakesleeanus. Analysis of the sequence revealed the presence of two short introns whose length and location were confirmed by sequencing a cDNA clone and comparing this with its genomic counterpart. The intron splice sites and the 5'- and 3'-noncoding flanking regions show general features of fungal genes. Northern-blot hybridization revealed the pyrG transcript to be approx. 1.0 kb. The M. circinelloides pyrG cDNA clone was able to complement the pyrF::Mu-1 mutation of Escherichia coli when inserted between bacterial expression signals. Additionally, the genomic clone complemented the M. circinelloides pyrG4 mutation. When an M. circinelloides autonomous replication sequence was included in the transforming plasmid, the average transformation frequency obtained was 600 to 800 transformants per micrograms DNA and per 10(6) viable protoplasts. PMID- 1628846 TI - Translational options for the pir gene of plasmid R6K: multiple forms of the replication initiator protein pi. AB - The autogenously controlled pir gene of plasmid R6K was believed to encode a single polypeptide that plays multiple roles in the plasmid's biology. We have isolated an opal (op) mutant at the 18th codon of the pir coding frame which does not totally abolish translation of pir mRNA. In extracts of cells containing this mutation two translational products (35 kDa and 30.2 kDa) have been detected. We propose that the 35-kDa polypeptide produced by the pir18 op mutation contains Trp substituted for Arg18 as the result of an opal readthrough. Translation, which results in the 30.2-kDa polypeptide, originates downstream from the UGA stop signal created by the mutation. Moreover, we realize now that the 30.2-kDa polypeptide is also produced in cells containing a wild-type (wt) pir gene. The shorter variant of the pi protein lacks replication initiation and inhibition functions, as well as autorepressor activity in vivo. We also show that an in frame fusion of seven N-terminal codons of the trpE gene with a pir gene lacking the first two codons produces two polypeptides which replace the 35-kDa pi protein and are of similar molecular weight. Thus, at least three options exist in the translation of the wt pir mRNA. Start codons are most likely at codon positions 1, 6 or 7, and 36 or 38. Each of these five AUG codons is preceded by a consensus ribosome-binding site (RBS). PMID- 1628847 TI - A genetic system to study the in vivo role of transcriptional regulators in Escherichia coli. AB - A genetic system for studying in vivo the interactions between a transcriptional regulatory protein and its target DNA has been developed for Escherichia coli. It is composed of two compatible plasmids: one high-copy-number promoter-probe vector, and one low-copy-number vector in which the gene encoding the desired protein is cloned under the control of an inducible promoter. The system was successfully tested for its specificity and for dosage analysis by using a combination of the plasmid pLS1-encoded RepA repressor and its target DNA. PMID- 1628848 TI - A general role for the lux autoinducer in bacterial cell signalling: control of antibiotic biosynthesis in Erwinia. AB - Micro-organisms have evolved complex and diverse mechanisms to sense environmental changes. Activation of a sensory mechanism typically leads to alterations in gene expression facilitating an adaptive response. This may take several forms, but many are mediated by response-regulator proteins. The luxR encoded protein (LuxR) has previously been characterised as a member of the response-regulator superfamily and is known to respond to the small diffusible autoinducer signal molecule N-(beta-ketocaproyl) homoserine lactone (KHL). Observed previously in only a few marine bacteria, we now report that KHL is in fact produced by a diverse group of terrestrial bacteria. In one of these (Erwinia carotovora), we show that it acts as a molecular control signal for the expression of genes controlling carbapenem antibiotic biosynthesis. This represents the first substantive evidence to support the previous postulate that the lux autoinducer, KHL, is widely involved in bacterial signalling. PMID- 1628849 TI - Cloning and primary structure of the wide-spectrum amidase from Brevibacterium sp. R312: high homology to the amiE product from Pseudomonas aeruginosa. AB - A Brevibacterium sp. R312 DNA fragment encoding the wide-spectrum amidase (EC 3.5.1.4) has been cloned and sequenced, using limited amino acid (aa) sequence information obtained from the purified enzyme. The deduced aa sequence showed more than 80% strict identity with the Pseudomonas aeruginosa aliphatic amidase, the product of the amiE gene, suggesting a horizontal transfer of the gene during evolution between Gram+ and Gram- bacteria. PMID- 1628850 TI - Molecular heterogeneity of plasma superoxide dismutase. AB - A method was worked out that helped us to isolate superoxide dismutase (SOD) from human blood plasma. The change of enzyme's activity was shown depending on the period of SOD storage. Changes in activity were observed in storing protein after gel filtration. The activity of purified enzyme was half as much after 24 h storage and remained constant for a long period of time (5 mo). The change of SOD activity was found to be connected with a modification of its structure. The storage of enzyme's solution during 3 1/2 mo is accompanied by the lowering of protein molecular mass from 53,000 Da to 34,000 Da. The inhibitors of proteinases -phenyl-methylsulfonyl fluoride (PMSF) and alpha 2-macroglobulin--showed no protective effects on purified SOD. That's why it was possible to say that the lowering of protein molecular mass didn't connect with a specific proteolysis. An oxidative modification of SOD structure is under discussion now. The modification is most probably caused by oxidative destruction of aminoacid residues that are located outside the protein active centre. PMID- 1628851 TI - Movement of methylphenazyl free radicals in polar and nonpolar liquids. AB - A protonated, charged free radical of methylphenazine methosulfate (PMS) was generated at carbon electrodes in a buffered aqueous medium. This radical diffused from the aqueous phase into nonpolar organic solvents, where it was stable for extended periods. The electron spin resonance (ESR) spectrum of the free radical species in the nonpolar solvent was significantly different from that of the aqueous species. This difference was attributed to the loss of electric charge through deprotonation at the solution interface, followed by solvation of the uncharged species in the organic phase. ESR spectra are presented for PMS free radicals in polar and nonpolar liquid phases, along with electrochemical results and conclusions regarding the mechanisms of movement and toxicity of phenazyl free radicals in biological systems. PMID- 1628852 TI - The effect of ascorbate supplementation on oxidative stress in the streptozotocin diabetic rat. AB - An increase in oxidative stress may contribute to the development of diabetic complications. The key aqueous-phase chain-breaking antioxidant ascorbate is known to be deficient in diabetes, and we have therefore investigated the effects of ascorbate supplementation on oxidative stress in the streptozotocin diabetic rat. Markers of lipid peroxidation (malondialdehyde [MDA] and diene conjugates) were increased in plasma and erythrocytes of untreated diabetic animals, and levels of the antioxidants ascorbate and retinol were reduced. Plasma tocopherol was unchanged. Insulin treatment normalized MDA and ascorbate levels, although ascorbate metabolism remained disturbed, as indicated by increased levels of dehydroascorbate. High-dose ascorbate supplementation in the absence of insulin treatment restored plasma ascorbate to normal and increased plasma retinol and tocopherol levels. However, MDA and diene conjugate levels remained unchanged, possibly as a result of increased iron availability. High-dose ascorbate supplementation should be approached with caution in diabetes, as ascorbate may exert both antioxidant and prooxidant effects in vivo. PMID- 1628853 TI - Oxidative stress on mouse embryo development in vitro. AB - Oxygen radicals are involved in the in vitro block phenomenon of embryo development, because a low oxygen tension and superoxide dismutase (SOD) have been shown to promote the in vitro development of mouse embryos. One of the target molecules damaged by oxygen radicals may be the thiol (SH) group of proteins because it is readily oxidized. In this study, we evaluated the effects of thioredoxin, which is a powerful protein disulfide reductase, on mouse (Institute of Cancer Research, ICR) preimplantation embryo development. Culture of mouse pronuclear embryos recovered 17 h after human chorionic gonadotrophin (hCG) administration in the presence of thioredoxin (200 micrograms/mL) significantly increased the blastulation rate (75.3%) when compared to the control culture system (8.9%). The effects of thioredoxin were observed only from the pronuclear stage to the two-cell stage (17-48 h after hCG administration). An additive effect of thioredoxin and SOD, or thioredoxin and a low oxygen tension, was observed. These results suggest that the oxidation of the SH group of proteins is one of the causes of developmental blockage of embryos in vitro. The target protein for reduction by thioredoxin has not been identified yet, but thioredoxin will be a new clue for clarifying the mechanism of blocking development in vitro. PMID- 1628854 TI - Tolerance and safety of vitamin E: a toxicological position report. AB - From numerous publications on the "prophylactic" and "therapeutic" use of vitamin E, it may be concluded that the toxicity of vitamin E is very low. It has been demonstrated in animal experiments that vitamin E has neither mutagenic, teratogenic nor carcinogenic properties. Based on studies in humans, a daily dosage of 100-300 mg vitamin E can be considered harmless from a toxicological point of view. Using double-blind studies involving a large number of subjects, it has been demonstrated that large oral doses of up to 3,200 USP-Units/day led to no consistent adverse effects. From a large body of published data, dosage ranges have been deduced which can be characterized as safe for human subjects even where their use extends over a long period of time. It should, however, be noted that oral intake of high levels of vitamin E can exacerbate the blood coagulation defect of vitamin K deficiency caused by malabsorption or anticoagulant therapy. High levels of vitamin E intake are, therefore, contraindicated in these subjects. PMID- 1628855 TI - Malondialdehyde production and ascorbate decrease are associated to the reperfusion of the isolated postischemic rat heart. AB - Isolated Langendorff-perfused rat hearts after 20 min of normoxic perfusion in the presence of 2.5 mM Ca++ and 11 mM glucose were subjected to 30 min of global normothermic ischemia followed by 30 min of normoxic reperfusion with the starting buffer. At the end of each perfusion condition, hearts were freeze clamped and deproteinized by 0.6 M HClO4. Two-hundred microL of the neutralized tissue extracts were analyzed by a recently developed high-performance liquid chromatography (HPLC) method for the simultaneous determination of malondialdehyde (MDA), ascorbic acid, and adenine nucleotides. By means of this analytical technique, it was possible to demonstrate that MDA is undetectable in control hearts. In contrast, 30 min of ischemia induced a modest production of MDA (0.012 mumol/g dw), while a large amount of MDA (0.103 mumol/g dw) was observed in reperfused hearts. Values referring to ascorbic acid showed that the concentration of this antioxidant progressively decreased from 1.190 (control hearts) to 0.837 (ischemic hearts) and to 0.595 mumol/g dw (reperfused hearts). The overall conclusions of this study are that reperfusion induces an oxidative stress to the isolated myocardium, a decrease of ascorbate, and an increase of lipid peroxidation. Therefore, by means of a proper analytical method, MDA may represent a valid biochemical parameter to demonstrate the relationship between myocardial reperfusion and a detectable tissue damage. PMID- 1628856 TI - Pholasin: a new chemiluminescent probe for the detection of chloramines derived from human phagocytes. AB - We have previously reported that normal human polymorphonuclear neutrophils (PMN) release taurine-chloramine, a long-lived oxidant, in response to stimulation by phorbol myristate acetate (PMA) or opsonized zymosan in the presence of exogenous taurine. We now describe a new, simple, and highly sensitive method for the detection of chloramines, including taurine-chloramine, using the chemiluminescent probe Pholasin, the luciferin of the mollusc Pholas dactylus. Taurine-chloramine (N-chlorotaurine) detection was assessed with both a colorimetric method (based on the oxidation of potassium iodide) and with the Pholasin-dependent chemiluminescence (CL) method. The taurine-chloramine concentration in PMN supernatants determined using the potassium iodide (KI) method correlated closely with Pholasin-dependent CL. This CL was also assessed in nonoxidative conditions. No taurine-chloramine was detected in supernatants of lymphocytes and PMN from patients with an oxidative burst defect (chronic granulomatous disease, CGD) with the KI method, but Pholasin-dependent CL was consistently observed. The use of methionine, a specific chloramine scavenger in our incubation conditions, allowed us to define a methionine-inhibitable fraction of Pholasin-dependent CL (i.e., chloramine-induced CL). PMID- 1628857 TI - Peroxyl radical-mediated hemolysis: role of lipid, protein and sulfhydryl oxidation. AB - The objective of this study was to define the relationship between peroxyl radical-mediated cytotoxicity and lipid, protein and sulfhydryl oxidation using human erythrocytes as the target mammalian cell. We found that incubation of human erythrocytes with the peroxyl radical generator 2,2' azobis (2 amidinopropane) hydrochloride (AAPH) resulted in a time and dose-dependent increase in hemolysis such that at 50 mM AAPH maximum hemolysis was achieved at 120 min. Hemolysis was inhibited by hypoxia and by the addition of certain water soluble free radical scavengers such as 5-aminosalicylic acid (5-ASA), 4-ASA, N acetyl-5-ASA and dimethyl thiourea. Peroxyl radical-mediated hemolysis did not appear to involve significant peroxidation of erythrocyte lipids nor did they enhance protein oxidation at times preceding hemolysis. Peroxyl radicals did however, significantly reduce by approximately 80% the intracellular levels of GSH and inhibit by approximately 90% erythrocyte Ca(2+)-Mg2+ ATPase activity at times preceding the hemolytic event. Our data as well as others suggest that extracellular oxidants promote the oxidation of intracellular compounds by interacting with certain redox active membrane components. Depletion of intracellular GSH stores using diamide did not result in hemolysis suggesting that oxidation of GSH alone does not promote hemolysis. Taken together, our data suggest that neither GSH oxidation, lipid peroxidation nor protein oxidation alone can account for peroxyl radical-mediated hemolysis. It remains to be determined whether free radical-mediated inactivation of Ca(2+)-Mg2+ ATPase is an important mechanism in this process. PMID- 1628858 TI - Synergistic effects of Cu(II) and dimethylammonium 2,4-dichlorophenoxyacetate (U46 D fluid) on PM2 DNA and mechanism of DNA damage. AB - Dimethylammonium 2,4-dichlorophenoxyacetate (2,4-D . DMA) induced strand breaks in PM2 DNA when incubated with CuCl2, whereas 2,4-D . DMA alone or CuCl2 alone did not show any or only a negligible effect. The formation of single strand breaks increased linearly with time and concentration of 2,4-D . DMA. Neocuproine, a specific Cu(I) chelator totally prevented strand break formation. So did catalase (up to 100 mM 2,4-D . DMA), but DMSO had only a small protective effect. 2,4-Dichlorophenol, CO2 and formaldehyde were detected as reaction products of 2,4-D and CuCl2. From these results a redox reaction of Cu(II) and 2,4-D is proposed, which could explain the DNA damaging properties of CuCl2/2,4-D . DMA. PMID- 1628859 TI - Circadian rhythm of white blood cell aggregation and free radical status in healthy volunteers. AB - Previous studies have demonstrated circadian rhythms in the onset of thrombotic events, which occur most commonly in the morning, and also in the fibrinolytic activity of the blood which has a peak in the evening and a trough in the morning. There has recently been increasing interest in the role of white blood cells (WBCs) and free radicals (FRs) in thrombosis. No one has yet investigated the potential circadian variation of WBC aggregation and FRs in humans. We studied the circadian rhythm of WBC aggregation and FR status in 10 healthy male volunteers. Six blood samples were collected at 4 hourly intervals from 12:00 (mid-day) until 08:00 the following morning. The volunteers carried out normal daily activities until 00:00 at which time they went to bed and they remained in bed until 08:00. The following were measured on each sample: WBC aggregation; thiobarbituric acid reactive substances (TBARs), plasma thiols (PSH), red cell lysate thiols (LSH), glutathione (GSH) and superoxide dismutase (SOD) which are all altered in the presence of FR activity. The following parameters demonstrated significant circadian rhythms, WBC aggregation p less than 0.001, TBARs p less than 0.015, PSH p less than 0.001, LSH p less than 0.002. WBC aggregation was lowest at 09:00 and highest at 00:00-04:00. TBARs and PSH both had a peak at 16:00 and a trough at 04:00. LSH had a peak at 12:00 and a trough at 08:00. As the behaviour of WBCs and FR status influence the flow properties of blood, a circadian rhythm in WBC function and FR status may contribute to the time of onset of thrombotic diseases. Moreover, with many studies being currently undertaken in this area, our work indicates the need to standardize sample times. PMID- 1628860 TI - Study of the teratogenic potential of FD & C yellow No. 5 when given in drinking water. AB - FD & C Yellow No. 5 was available to pregnant Osborne-Mendel rats throughout gestation at dose levels of 0.05, 0.1, 0.2, 0.4 or 0.7% in solution in distilled drinking-water. Based on fluid consumption, the rats received 67.4, 131.8, 292.4, 567.9 and 1064.3 mg FD & C Yellow No. 5/kg body weight/day. Distilled water served as the control. No dose-related changes were seen in mean daily food consumption or maternal body-weight gain. Starting during the second trimester of gestation, fluid consumption was significantly greater in the rats given 0.7% FD & C Yellow No. 5 than in the controls. The females were killed on gestation day 20. No dose-related changes were seen in maternal clinical findings, implantations, foetal viability or foetal size (weight and length). No dose related foetal terata were seen. Neither visceral development nor skeletal development (sternebral and other skeletal bones) was affected by the dye. The small numbers of statistically significant increases in skeletal variations in the 0.05 and 0.4% levels are considered random because they are not dose related. PMID- 1628861 TI - Developmental toxicity evaluation of inhaled citral in Sprague-Dawley rats. AB - Citral is a commonly used fragrance and flavour ingredient that has demonstrated a potential for teratogenicity in chick embryo screening studies. To investigate potential mammalian developmental toxicity, pregnant Sprague-Dawley rats were exposed to citral by inhalation for 6 hr/day on gestation days 6-15 at mean concentrations of 0, 10 or 34 ppm as vapour, or 68 ppm as an aerosol/vapour mixture. Dams were killed on gestation day 20 and the foetuses were removed and evaluated for gross, visceral and skeletal malformations. Exposure to 68 ppm was maternally toxic, with reduced body-weight gains, ocular opacity, breathing difficulty, nasal discharge and salivation noted in the dams. No maternal toxicity was seen at the lower vapour exposure levels. The number of corpora lutea, implantations, resorptions, foetal viability, litter size, and sex ratio were not adversely affected by citral at any exposure level tested, and no exposure-related malformations were observed. At a maternally toxic exposure level, a slight reduction in mean foetal body weight and a slight increase in the incidence of hypoplastic bones were noted. Results of this study indicate that citral does not produce developmental toxicity in the rat when administered by inhalation at concentrations up to a maternally toxic exposure level. PMID- 1628862 TI - Initial studies on the toxicokinetics of fumonisin B1 in rats. AB - Fumonisin B1 (FB1), the major compound in the fumonisin group of secondary metabolites of Fusarium moniliforme Sheldon, is associated with some human and animal diseases. After intraperitoneal dosing to rats (7.5 mg/kg), FB1 was rapidly absorbed and reached a maximum concentration in plasma within 20 min after injection. Thereafter, it underwent rapid removal from plasma, displaying a mono-exponential elimination phase that fitted a one-compartment model with a half-life of 18 min. Collection of 24- and 48-hr urine samples indicated that only 16% of the applied dose was eliminated unmetabolized in urine, all within the first 24-hr period following dosing. In contrast to this, a similar dose of FB1 given by gavage resulted in the recovery of only 0.4% of the FB1 in urine. PMID- 1628863 TI - Faecal elimination of lead and cadmium in subjects on a mixed and a lactovegetarian diet. AB - Faecal elimination of lead and cadmium in 16 subjects who changed from a mixed diet to a lactovegetarian diet has been studied. The faecal weight increased significantly following the change to the vegetarian diet, partly because of increased water content. There was a large inter-individual variation in faecal elimination of lead and cadmium during both the mixed-diet period (range 14 to 118, median 31 micrograms Pb/day; range 4.5 to 21, median 12 micrograms Cd/day) and the vegetarian diet period (range 19 to 136, median 42 micrograms Pb/day; range 6.1 to 24, median 14 micrograms Cd/day). There was a tendency towards increased faecal elimination of lead and cadmium following the change to the vegetarian diet, but the differences were not statistically significant. PMID- 1628864 TI - Antimutagenicity of ellagic acid towards the food mutagen IQ: investigation into possible mechanisms of action. AB - The ability of the plant phenol ellagic acid to inhibit the mutagenicity of the food mutagen IQ was evaluated using Salmonella typhimurium strain TA98 in the Ames mutagenicity test. Ellagic acid caused a concentration-dependent decrease in the S-9- and microsome-mediated mutagenicity of IQ. The plant phenol did not interact directly with the IQ-derived mutagenic species and did not modify the cytosol-mediated activation of the promutagen. At the concentrations used in the mutagenicity studies, ellagic acid failed to inhibit microsomal mixed-function oxidase activity, including that mediated by the P450I family responsible for the bioactivation of IQ, despite being an essentially planar molecule as indicated by computer-graphic analysis. The inhibitory effect of ellagic acid was independent of its ability to chelate Mg2+. However, pre-incubation of ellagic acid with the bacteria, followed by removal of the plant phenol, did not completely prevent the inhibitory effect of the phenol on the mutagenicity of IQ. Intraperitoneal administration of ellagic acid to rats caused a decrease in total cytochrome P 450 levels and related activities as well as in cytosolic glutathione S transferase activity. Finally, the possibility that the reported anticarcinogenic action of ellagic acid reflects nothing more than non-selective destruction of hepatic cytochromes P-450, and thus reduced chemical activation, is considered. PMID- 1628865 TI - Induction of reversible urothelial cell hyperplasia in rats by clorsulon, a flukicide with weak carbonic anhydrase inhibitory activity. AB - Clorsulon, a flukicide registered for use in treating Fasciola hepatica infections in cattle, has induced urinary bladder urothelial cell hyperplasia in rats at oral doses of 30 mg/kg/day or more. Despite previous testing at doses above this threshold, this lesion had not been found in subchronic or chronic toxicity studies in rats. After ruling out the presence of a contaminant as the causative factor in producing this lesion, a study was conducted in which clorsulon increased the pH and altered the electrolyte composition of urine, consistent with its weak carbonic anhydrase inhibitory activity. The acid/base balance of the diet markedly affected the threshold for induction of the urothelial cell hyperplasia: acidification by addition of 5% ammonium chloride to the diet reduced the incidence and severity. In additional studies it was found that the urothelial cell hyperplasia was most pronounced after 1 week of treatment compared with daily exposure for either 5 or 15 wk. The reversibility of the hyperplasia despite continued treatment confirms that the hyperplasia is not a preneoplastic lesion, a conclusion supported by negative studies of carcinogenicity in rodent bioassays of clorsulon and other drugs with carbonic anhydrase inhibitory activity. PMID- 1628866 TI - Proliferation and morphological transformation of BALB/3T3 cells by a prolonged treatment with sodium orthovanadate. AB - BALB/3T3 mouse embryo cells were used to study the effect of sodium orthovanadate on cell proliferation and morphological transformation. In the presence of the chemical (0.25-1.0 micrograms/ml), the cells continued to proliferate after the cultures were confluent. However, contact-inhibited growth was resumed after removal of the chemical from the culture medium. Continued exposure of the cells to the chemical for 4 wk led to the production of numerous foci consisting of morphologically transformed cells. In contrast, as in vitro transformation assay with a 48-hr treatment protocol followed by 4 wk of incubation without the chemical produced negative results. To test the stability of the transformed foci that were produced on prolonged exposure, we isolated 20 foci with distinctly transformed characteristics from treated cultures and grew them in medium without orthovanadate. 15 isolates gradually reverted to contact-inhibited growth and five maintained the transformed phenotype through ten serial subcultures. The results show that the majority of the transformed foci from the orthovanadate treated culture failed to maintain transformed characteristics in the absence of the chemical. However, a small fraction of the foci appeared to be altered permanently and exhibited a transformed phenotype in the absence of the chemical. PMID- 1628867 TI - Statistical evaluation of the fixed-dose procedure. AB - The fixed-dose procedure (FDP) was proposed by the British Toxicology Society in 1984 as an alternative to the LD50 study in the assessment of the acute oral toxicity of a substance. This paper presents a statistical evaluation of this procedure. A mathematical description of the FDP shows that the starting dose can affect the toxic classification of a substance. The toxic classification based on the FDP is compared with that based on an LD50 test. This shows that, in general, the FDP is likely to result in the same classification or a less toxic one than the LD50 procedure. However, for substances with very shallow dose-response slopes, the FDP is likely to result in the same classification or a more toxic one. The expected number of animals that will be tested and will die using the FDP will be reduced compared with the LD50 study. The results from the international validation study carried out in 1989 showed agreement with the results predicted from the mathematical model. PMID- 1628868 TI - Nitrosamines in rubber bands used for orthodontic purposes. AB - Fourteen samples from eight brands of elastic-rubber bands used in orthodontics were tested for their nitrosamine content. The presence of N-nitrosodibutylamine and N-nitrosopiperidine was confirmed. The potential for nitrosamine formation from accelerating agents used for vulcanization and from other nitrosatable amines, which may be present in rubber exposed to salivary nitrite, justifies further investigations. PMID- 1628869 TI - Carcinogenic chemicals in food: evaluating the health risk. AB - The presence of a low level of potentially harmful chemicals in food continues to be a concern to many individuals. A major concern is that these chemicals, which can be synthetic or naturally occurring, may be a causative factor in human cancer. Synthetic chemicals in food may be present either as specific additives or as contaminants derived from environmental or agricultural chemicals. Food also contains a variety of naturally occurring chemicals derived from vegetables or other plants. These may in some cases be considered as contaminants, and are occasionally used as specific additives. New chemicals can also be formed during the cooking or preserving processes. The capacity of any of these chemicals to induce cellular damage and mutation is minimized by natural defence systems such as an efficient cellular detoxification system and DNA repair. The factors influencing tumour formation in humans are numerous and interrelated and exposure to minor dietary chemicals needs to be considered in this context. Thus, the results of animal carcinogenicity assays on individual chemicals need to be interpreted with care, taking into account the mechanisms by which mutagenic and other chemicals initiate cancer, as well as the level of human exposure to these chemicals. Further research is necessary to determine the role, if any, of minor dietary components in tumour formation. Meanwhile, there needs to be a more holistic approach to the multitude of factors, including total diet, that may influence human cancer incidence. In this way, the relative risk of dietary chemicals may be given a more meaningful perspective for health professionals and consumers alike. PMID- 1628870 TI - Propionic acid and the phenomenon of rodent forestomach tumorigenesis: a review. AB - Propionic acid (PA) is widely used as an antifungal agent in food. It is present naturally at low levels in dairy products and occurs ubiquitously, together with other short-chain fatty acids (SCFA), in the gastro-intestinal tract of humans and other mammals as an end-product of the microbial digestion of carbohydrates. It has significant physiological activity in animals. PA is irritant but produces no acute systemic effects and has no demonstrable genotoxic potential. Rats receiving PA at 4% in the diet develop hyperplastic lesions and tumours of the forestomach. Such changes are also reported to have been produced by a variety of other chemicals, mechanical and chemical irritants, parasites, and even various dietary insufficiencies or imbalances. Evidence suggests that repeated or persistent damage to cells of the forestomach epithelium and associated proliferative responses may be a common factor in rodent forestomach tumorigenesis. Although humans do not have a forestomach, the mouth, pharynx and oesophagus are lined with similar epithelium and thus are potential target organs. However, food contact time is considerably less in these organs than in the rodent forestomach. On current evidence, PA cannot be considered a carcinogenic risk to humans; nevertheless, to determine a safe level of dietary exposure it is suggested that no-observable-effect levels should be determined for epithelial cell damage and proliferative responses in the squamous mucosa of laboratory animals, particularly in those parts of the gastro-intestinal tract having a counterpart in humans, such as the pharynx and oesophagus. PMID- 1628871 TI - [Individualized therapy of fat metabolism disorders. Focusing on total cardiovascular risk]. PMID- 1628872 TI - [ESVEM-Study. Life threatening arrhythmias can be controlled. Symposium: Clinical Trials. American College of Cardiology 41st annual scientific sessions. Dallas, Texas, 12-16 April 1992]. PMID- 1628874 TI - [Consultation: Acute and chronic disorders of the locomotive apparatus]. PMID- 1628873 TI - [Heart diseases in light of SAVE-Study. Captopril improves prognosis and symptoms of left ventricular dysfunction after myocardial infarction. 41st scientific annual meeting of the American College of Cardiology. Dallas, Texas, 12-16 April 1992]. PMID- 1628875 TI - Potassium channels of the insulin-secreting B cell. AB - Ionic and electrical events play a central role in the stimulus-secretion coupling of the pancreatic B cell. Potassium permeability is critically involved in the regulation of B cell membrane potential and insulin secretion. In the absence of glucose, membrane potential remains stable, around -65 mV. This resting potential is mainly determined by the high potassium conductance of the membrane. The ATP generated by glucose metabolism in B cells blocks the K+(ATP) channels controlling resting membrane potential. Thus, glucose metabolism leads to closure of the ATP-dependent potassium channels; the resulting decrease in K+ permeability induces depolarization and opening of voltage-activated Ca-channels. The subsequent increase in Ca2+ influx raises the cytoplasmic concentration of free Ca2+, which in turn triggers exocytosis of secretory granules. Other types of K+ channels have also been identified in the B cell, such as voltage- and Ca(2+)-dependent K+ channels, which are not a target for the action of glucose, but may play a role in the repolarization of spikes. The modulation of insulin release by some hormones and neurotransmitters involves, among other mechanisms, an interference with the plasma membrane K+ conductance. Thus, galanine, somatostatin and adrenaline, which inhibit insulin release, increase K+ conductance by a G protein-dependent mechanism; both peptides were reported to open ATP-sensitive K+ channels in insulin-secreting cell line RINm5F. It was also observed that extracellular purine nucleotides could interfere with K+ channels. Among the various drugs interfering with insulin secretion, sulfonylureas, such as tolbutamide and glibenclamide, directly inhibit ATP-dependent K+ channels in the B cell membrane and thereby initiate insulin release. In contrast, potassium channel openers such as diazoxide, antagonize the effects of glucose by increasing K+ permeability of the B cell membrane. Furthermore, other classes of drugs have recently been shown to interact with K+ (ATP) channels. Thus, K+ channels of the pancreatic B cell, particularly ATP-dependent ones, play a crucial role in the electrophysiology of insulin secretion; they are an important target for pharmacological agents designed to modulate this secretion. PMID- 1628876 TI - The role of monoamine oxidase in the metabolism of exogenous noradrenaline by the human saphenous vein. AB - Human saphenous vein segments were obtained from patients subjected to coronary bypass surgery. As determined by HPLC-ED, the veins had a relatively low content of noradrenaline and high content of the deaminated metabolites, dihydroxyphenylglycol (DOPEG) and dihydroxymandelic acid (DOMA). In vein segments which had been incubated with 3H-noradrenaline (0.1 mumol/l), the oxidative deamination pathway predominated over the O-methylating one. Deamination occurred both at the neuronal and extraneuronal level; DOPEG appearing to be a good index of intraneuronal deamination, whereas DOMA and O-methylated and deaminated metabolites were mainly formed extraneuronally. Both MAO type A and MAO type B selective inhibitors reduced the deamination of noradrenaline; deamination was also found to be partially sensitive to semicarbazide. Inhibition of neuronal uptake or of deamination increased O-methylation. The human saphenous vein thus metabolizes exogenous noradrenaline following a pattern which substantially differs from that shown to occur in various blood vessels from other animal species. PMID- 1628877 TI - Further evidence that propentofylline (HWA 285) influences both adenosine receptors and adenosine transport. AB - We have examined the actions of a novel xanthine derivative, propentofylline (HWA 285), that has been shown to protect against ischemic brain damage in rats and gerbils, on adenosine receptors (A1 and A2), and on adenosine transporters using several techniques, cells and tissues. Propentofylline and its hydroxylated metabolite A 72 0287 were about 20 times less potent than theophylline in displacing A1-agonist binding to membranes from rat cortex, and A1-antagonist binding to whole DDT, MF-2 smooth muscle cells. A1-agonist binding to adenosine A1-receptors in several brain structures was inhibited in a concentration dependent manner by A 72 0287 and propentofylline as judged by quantitative autoradiography (IC50-values 300-600 microM in eg striatum and in cortex layer IV). In two functional assays, A1-receptor mediated effects were blocked by propentofylline. A1-receptor-mediated inhibition of cyclic AMP accumulation was virtually abolished by 100 microM propentofylline. The A1-receptor-mediated inhibition of evoked acetylcholine release was also reduced by propentofylline, but in this case the effect is not due exclusively to adenosine receptor antagonism but also to another action since the presynaptic inhibitory effect of carbachol was also inhibited. Adenosine A2-receptors were also antagonized by propentofylline as judged by a concentration-dependent antagonism of A2-agonist induced cAMP accumulation in human T-leukemia cells (possessing putative A2b receptors; pA2-value 180 microM compared to 0.26 microM for 8-cpt), and in PC-12 cells (possessing putative A2a-receptors, Ki-value 365 microM). Finally, adenosine transporters were affected by propentofylline and A 72 0287. Thus, [3H] nitrobenzylthioinosine-binding to guinea-pig cardiac membranes was blocked by propentofylline or A 72 0287 (Ki 270 microM). The present results show that propentofylline and its hydroxylated metabolite can influence adenosine mechanisms in a multitude of ways. How these different actions may contribute to the ability of propentofylline to reduce the magnitude of ischemic damage is discussed. PMID- 1628878 TI - Medical waste disposal in the dental office. PMID- 1628879 TI - Taking dentistry to the airwaves. PMID- 1628880 TI - Removable fixed bridge. PMID- 1628881 TI - Custom intra-coronal attachments for cosmetic removable partial dentures. PMID- 1628882 TI - An alternative method for the application of superficial heat. PMID- 1628884 TI - Using an office manual to fine-tune organizational effectiveness. PMID- 1628883 TI - An increasing Hispanic population and the practice of dentistry. PMID- 1628885 TI - 40 years of change: dental school applicants and students. PMID- 1628886 TI - How to increase your practice productivity. PMID- 1628887 TI - Molecular cloning, expression and characterization of the ovine IL-2R alpha chain. AB - Interleukin-2 (IL-2) stimulates the proliferation of activated antigen-specific T cells through its interaction with high affinity receptors. This event is largely regulated by the inducible expression of the alpha-chain (CD25) which, in combination with the beta-chain and possibly additional chains, forms the high affinity IL-2 receptor (IL-2R) complex. From a concanavalin A (Con A)-activated ovine T-cell complementary DNA (cDNA) library we have isolated two cDNA clones which together constitute a 2650 base pair (bp) messenger RNA (mRNA) species encoding the ovine IL-2R alpha chain. The nucleotide sequence has high homology with analogous cDNA from other species and predicts a mature protein of 254 amino acids. In addition to the predominate 2.6 kilobase (kb) ovine IL-2R alpha chain mRNA species. Northern blot analysis of activated T-cell RNA revealed two larger mRNA species. The ovine IL-2R alpha chain cDNA was transfected into CHO cells and low affinity binding of human recombinant IL-2 demonstrated. Polyclonal antisera generated against the transfected cells cross-reacted with Con A-activated ovine lymphocytes. In addition these antisera were used to immunoprecipitate a unique 50,000 MW protein from the transfected cells. It is likely that this protein represents the expressed ovine IL-2R alpha chain cDNA which is heavily glycosylated as distinct from the 30,869 MW primary translation product. Southern blot analysis of ovine genomic DNA suggests that the ovine IL-2R alpha chain is encoded by a single copy gene. PMID- 1628888 TI - Induction of the expulsion of Strongyloides ratti and retention of Nippostrongylus brasiliensis in athymic nude mice by repetitive administration of recombinant interleukin-3. AB - A repetitive administration of recombinant interleukin-3 (rIL-3), which can induce the expulsion of Strongyloides ratti in athymic nude mice, did not affect the expulsion of Nippostrongylus brasiliensis. Nude mice infected with N. brasiliensis were injected i.p. with a total of 6.8 x 10(5) U rIL-3 or medium twice a day from Day 5 to Day 11 post-infection. The kinetics of expulsion estimated by egg excretion in faeces up to Day 20 post-infection and adult worm burden on Day 21 was not affected by the IL-3 administration. A similar administration with a higher dose (total 10.6 x 10(5) U) of rIL-3 did not alter the adult worm burden on Day 13. The number of intestinal mucosal mast cells on Day 13 was markedly increased by the treatment, although the number of intestinal goblet cells was comparable between the treated and control mice. When nude mice were infected concurrently with N. brasiliensis and S. ratti and then injected repeatedly with rIL-3 (total 2.2 x 10(5) U) from Day 5 to Day 11, adult worms of S. ratti were expelled from the small intestine by Day 13; however adult worms of N. brasiliensis were retained. Again in the concurrent infection, the number of intestinal mucosal mast cells was significantly increased but that of intestinal goblet cells was not altered by the rIL-3 administration. These results indicate that the expulsion of S. ratti is dependent on IL-3 whereas that of N. brasiliensis is less dependent on IL-3. PMID- 1628889 TI - Cytotoxic activity of intestinal lamina propria lymphocytes on human immunodeficiency virus (HIV)-infected cells. AB - The phenotype and cytotoxic activity of lamina propria lymphocytes (LPL) from the colorectal mucosa have been investigated primarily to analyse the role of LPL in human immunodeficiency virus (HIV) infection. The results reported here show that LPL strictly required a proliferative stimulus [either interleukin-2 (IL-2) or phytohaemaglutinin (PHA) to develop strong in vitro cytotoxicity, since freshly isolated LPL do not exhert cytotoxicity against either natural killer (NK) sensitive or NK-resistant target cells. The cytotoxicity of activated LPL against a large panel of myeloid tumours or colorectal carcinoma target cells shows the irrelevance of the tissue origin of target cells. Moreover, activated LPL lysed HIV-infected H9 cells more efficiently than peripheral blood lymphocytes (PBL), and were susceptible to HIV infection. In contrast, unstimulated LPL failed to be cytotoxic and susceptible to HIV. Thus, we strongly suggest that for the lymphocytes of the colorectal mucosa expression of cytotoxic activity and susceptibility to HIV-infection show two faces of the same coin, and therefore may be relevant in understanding the mechanisms and paths of transmission of HIV infection. PMID- 1628890 TI - Influence of H-2 genes on growth of Mycobacterium tuberculosis in the lungs of chronically infected mice. AB - Mice infected by intraperitoneal injection of Mycobacterium tuberculosis were studied over a 23-week period. They showed progressive infection in the lung (with increasing microbial count and granuloma size) whereas viable bacillary counts remained largely stationary in the spleen and in the liver. The influence of H-2 genes on the progression of the lung infection was studied in four congenic strains of animals with B10 and three congenic strains of animals with BALB backgrounds. H-2k mice had significantly higher bacterial counts in the lung than H-2b mice on both B10 and BALB backgrounds, BALB. K (H-2k) mice were also more susceptible than BALB/c (H-2d) mice. Results with recombinant strains showed that bacillary counts and granulomatous infiltration were lower in the B10 (KbAbE Db) compared with B10.A(3R) (KbAbEbDd) strain and in B10.A(4R) (KkAkE-Db) compared with B10.BR (KkAkEkDk) mice. This resistance to the late expansion of tuberculous infection in the lungs may be associated with the lack of an expressed I-E molecular or with the expression of the Db molecule. PMID- 1628891 TI - Susceptibility to Theiler's virus-induced demyelinating disease correlates with astrocyte class II induction and antigen presentation. AB - Theiler's murine encephalomyelitis virus (TMEV) is a picornavirus which induces a chronic demyelinating disease of the central nervous system (CNS) in certain susceptible mouse strains. Demyelination has been shown to result from immunopathological responses mediated by CD4+, major histocompatibility complex (MHC) class II-restricted T cells. As little or no class II is expressed in the normal mouse CNS, the ability of astrocytes to express these proteins and present antigen to T cells from TMEV-infected mice was investigated here. It is shown that astrocytes are capable of presenting TMEV to virus-specific T cells in vitro, and that this ability is dependent on prior induction of MHC class II by interferon-gamma (IFN-gamma) treatment. Unlike other viruses such as murine hepatitis virus-JHM (a coronavirus) and measles, TMEV is not capable of inducing class II on astrocytes directly. There is a correlation between the ease of class II induction on astrocytes from different mouse strains by IFN-gamma and mouse strain susceptibility to TMEV-induced demyelinating disease. These results suggest that following viral infection and initial T-cell infiltration into the CNS, class II induction on astrocytes is a key step allowing local antigen presentation and amplification of immunopathological responses within the CNS and hence the development of demyelinating disease. PMID- 1628892 TI - Human monoclonal antibodies specific for blood group antigens demonstrate multispecific properties characteristic of natural autoantibodies. AB - A panel of 72 human monoclonal antibodies with specificities for blood group antigens, A, Rh D, Rh C, Rh c, Rh E, Rh e, Rh G, Jka and Jkb, has been established from the peripheral blood of deliberately immunized donors. Previous work has established that the antibodies are highly specific for their respective blood group antigens, and a number of them are in routine clinical use as blood grouping reagents. This panel was screened for reactivity against six unrelated foreign and autoantigens by ELISA, for rheumatoid factor activity by ELISA and agglutination techniques, and for reactivity with a number of different tissues by immunofluorescence. Binding of the monoclonal antibodies to unrelated exo- and autoantigens was commonly seen amongst the antibodies of the IgM class, and to a lesser degree amongst the IgG class, with reaction patterns similar to those given by natural autoantibodies. Only five of the IgM antibodies failed to demonstrate any unexpected cross-reactivities and these included 1/13 anti-D, 2/7 anti-E, 1/13 anti-c and 1/2 anti-A. We propose that rather than natural autoantibodies representing a distinct population of immunoglobulins, multispecificity (polyspecificity, or polyreactivity) may be a feature of antibodies produced in response to exogenous antigens. The implications of this for the study of autoantibodies are discussed. PMID- 1628893 TI - Stimulatory effect of interleukin-1 beta on the interferon-gamma-dependent HLA-DR production. AB - Expression of major histocompatibility complex (MHC) class II genes is induced by interferon-gamma (IFN-gamma) in antigen-presenting cells. When human leukaemia THP-1 and PL-21 cells were pretreated with phorbol ester, IFN-gamma-dependent induction of MHC class II gene was markedly enhanced. To elucidate the mechanism of the phenomenon, we examined the effect of cytokines which were secreted from THP-1 cells by the treatment of phorbol ester. Among those cytokines, interleukin 1 beta (IL-1 beta) had a positive effect on IFN-gamma-dependent induction of MHC class II genes. In order to rule out the possibility that different clones of THP 1 cells respond independently to IFN-gamma or phorbol ester, we showed that all independent single clones expressed MHC class II and produced IL-1 beta by IFN gamma or phorbol ester, respectively. PMID- 1628894 TI - Induction of IgE antibodies in mice with recombinant grass pollen antigens. AB - In this study, recombinant Poa pratensis (Poa p) IX allergens were examined for their in vivo allergenicity and antigenicity. Immunization of mice with a fusion protein (FP) comprising beta-galactosidase and recombinant KBG8.3 (rKBG8.3) allergen induced high titres of both IgG and IgE antibodies. By contrast, immunization with rKBG60.2, which represents the N-terminal fragment of rKBG8.3, induced only IgG antibodies. The IgE antibody titre specific to Kentucky Bluegrass (KBG) was significantly higher than that to beta-galactosidase. Moreover, KBG-specific IgE antibodies showed no apparent decrease in their titres until 60 days after immunization, whereas the beta-galactosidase-specific IgE antibodies disappeared after 40 days. The antibodies induced with rKBG8.3 in mice were capable of inhibiting the binding of human IgE antibodies to KBG pollen allergens, which indicated that rKBG8.3-specific murine antibodies recognized epitopes similar to those recognized by human IgE antibodies. Analysis of allergenic cross-reactivities of rKBG8.3 with components from five other species of grass pollens revealed that IgE antibodies induced by this allergen are capable of binding in vivo to components from other grass pollens. These results suggest that the mouse may serve as a model for the manipulation of IgE responses to recombinant allergens or their chemically modified derivatives. PMID- 1628895 TI - Enhanced secretory IgA and systemic IgG antibody responses after oral immunization with biodegradable microparticles containing antigen. AB - Intragastric immunization may lead to the induction of antibodies in the secretory immune system including saliva. The antibody response is usually short lived. The objectives of this study were to see whether oral immunization with biodegradable microparticles containing antigen might lead to enhanced mucosal responses. Ovalbumin (OVA) was entrapped in a novel antigen delivery system comprising poly (D,L-lactide-co-glycolide) (PLGA) microparticles. Salivary IgA and serum IgG responses after three daily oral immunizations in BALB/c mice were assayed by ELISA at weekly intervals and compared with those to soluble antigen. Low levels of salivary IgA antibodies were detected at Weeks 2 and 3 in both groups and no significant differences were found. After a secondary series of intragastric immunizations at Week 4, marked differences were apparent between the groups. The mean salivary IgA titre at Week 6 was 959 +/- 494 U compared with 30 +/- 5 in the soluble OVA group (P less than 0.0001). Significant differences were still apparent at Weeks 7-8 through the value was falling. Serum IgG antibodies were detectable and were significantly greater in the particle group (at Weeks 4 and 8) than in controls (P less than 0.001). These results suggest that microparticles are taken up by antigen-presenting cells in Peyer's patches, then slowly degrade in vivo and release entrapped antigens, and thus can function as potent antigen delivery systems giving rise to both mucosal and systemic responses. Microparticles have considerable potential as a controlled released antigen delivery system for the induction of longer-term immune responses at mucosal surfaces. PMID- 1628896 TI - Tissue localization of conglutinin, a bovine C-type lectin. AB - The distribution of bovine conglutinin (BK) in sections of frozen bovine tissues was studied by the indirect immunoperoxidase technique using a monospecific rabbit anti-BK antibody. BK was found in the cytoplasma of all hepatocytes, indicating that the liver is a major site of synthesis of BK. In the germinal centres of the spleen, tonsils and lymph nodes the anti-BK staining was restricted to a population of cells with a distribution and morphology characteristic of follicular dendritic cells. Macrophages in lung and thymus, and glia cells in cerebrum, revealed a granular staining reaction within the cytoplasma. Endothelial cells of blood vessels reacted with anti-BK. The intensity of this reaction varied greatly between the organs, the most pronounced reaction being seen in the glomeruli of the kidney, and in the capillary sinusoides of the cortex of the adrenal gland. The high endothelial venules of lymph nodes and tonsils were also stained. These findings suggest that BK, which until now has been described only as a circulating molecule, may exhibit a biological function within the BK-positive tissues. PMID- 1628897 TI - Stimulation of tumour necrosis factor release by cytotoxic analogues of platelet activating factor. AB - The capacity of cytotoxic analogues of platelet-activating factor (PAF) to stimulate tumour necrosis factor-alpha (TNF-alpha) synthesis and release by human monocytes was determined. Cell-associated TNF-alpha was quantified by protein immunoblotting and released TNF-alpha was quantified by cytotoxicity bioassay. Picomolar concentrations of methoxyPAF, SDZ 62-759, SDZ 68-826, SDZ 62-434 and SRI 62-834 induced a two- to fivefold increase in cell-associated and released TNF-alpha. These compounds were as potent as PAF for stimulating monocytes. In contrast, they lacked direct platelet-activating activity and inhibited platelet aggregation induced by PAF selectivity. The analogues inhibited PAF binding to platelets but not to monocytes. The PAF binding antagonists kadsurenone, BN52021 and WEB2086 inhibited TNF-alpha release induced by 10(-11) M PAF or methoxyPAF by a maximum of only 30-60% whereas they inhibited platelet aggregation by 10(-8) M PAF completely. Monocyte receptors for methoxyPAF were evaluated. Scatchard analysis of [3H]methoxyPAF binding to monocytes revealed large numbers of relatively low affinity receptors (Kd = 5.9 +/- 0.5 x 10(-7) M; 9.1 +/- 4.2 x 10(7) sites/monocyte). These values do not correspond to binding constants of monocyte receptors for PAF and do not account for monocyte activation by picomolar concentrations of methoxyPAF. Cytotoxic analogues of PAF stimulate TNF alpha synthesis and release but they do not stimulate monocytes by interacting with PAF receptors. PMID- 1628898 TI - Antibodies against phosphatidylinositol and inositol monophosphate specifically inhibit tumour necrosis factor induction by malaria exoantigens. AB - The active component of the exoantigens of malarial parasites which stimulates macrophages to secrete tumour necrosis factor (TNF) has been shown to depend upon a phospholipid, the activity of which was blocked by phosphatidylinositol (PI) and inositol monophosphate (IMP) in competitive inhibition studies. Antisera made against the exoantigens of Plasmodium yoelii, which inhibited their induction of TNF, were found by an ELISA assay to contain antibody against several other phospholipids. However, the inhibitory antibody was removed specifically by adsorption with liposomes containing PI, but not other phospholipids. Furthermore, PI was the only phospholipid in non-liposomal form which induced the production of inhibitory antisera. Mice immunized with IMP, but not inositol, also produced inhibitory antisera. When incorporated into liposomes several other phospholipids did give rise to inhibitory antibodies but, in contrast to the antisera against parasite exoantigens, PI and IMP, the inhibitory activity was removed by adsorption with heterologous phospholipid liposomes, suggesting that it was directed against a common determinant, presumably the phosphate ester head group. Inhibitory antibodies in the antisera tested were predominantly IgM and titres were not increased after repeated injections. Antisera raised against PI, IMP or the cross-reacting phospholipid liposomes also inhibited TNF secretion by macrophages stimulated by exoantigens of the human parasites P. falciparum and P. vivax, but not by bacterial lipopolysaccharide. These findings confirm our conclusion that exoantigens from these different species contain phosphate bound to inositol in their TNF-inducing moiety. PMID- 1628899 TI - Detection of inflammatory cytokine messenger RNA (mRNA)-expressing cells in human inflamed gingiva by combined in situ hybridization and immunohistochemistry. AB - Cells expressing messenger RNA (mRNA) for inflammatory cytokines [interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-8] were demonstrated by in situ hybridization in human inflamed gingiva. When this technique was used in conjunction with immunohistochemistry, IL-1 alpha and/or beta and IL-8 messages were observed predominantly on macrophages infiltrating the gingiva. TNF alpha messages were abundant on macrophages and T cells. In contrast, the IL-6 mRNA were more widely distributed on many types of cells such as macrophages, T cells, fibroblasts, endothelial cells and B cells. This study clearly identified the cells which express mRNA for inflammatory cytokines in inflamed gingiva and suggested an involvement of cytokine network in the generation of human periodontitis. PMID- 1628900 TI - Paradoxical stimulation and inhibition by protein kinase C modulating agents of lipopolysaccharide evoked production of tumour necrosis factor in human monocytes. AB - Human blood monocytes were activated by bacterial lipopolysaccharide endotoxin (LPS) (10 ng/ml) for cytotoxicity of WEHI-164 mouse fibrosarcoma cells, determined by release of 51Cr from WEHI-164 tumour cells incubated with monocyte supernatants. The chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (FMLP) augmented LPS-induced cytotoxicity but had no effect alone. FMLP but not LPS stimulated phospholipase C (PLC), determined by the release of [3H]inositol phosphates. Addition of tumour promoter and protein kinase C stimulant, phorbol 12-myristate-13-acetate (PMA) at concentrations of 3 x 10(-10) M to 3 x 10(-9) M, resulted in an augmentation of 30-200% in LPS-evoked cytotoxicity. The effects of FMLP and PMA, like the effect of LPS alone, were completely blocked by antibody to recombinant human tumour necrosis factor-alpha (TNF-alpha), indicating that cytotoxicity induced by LPS, FMLP, and PMA were due solely to TNF release. Concentrations of PMA greater than 3 x 10(-9) M caused inhibition of TNF release. Okadaic acid (20 ng/ml), an inhibitor of phosphatases I and IIa, augmented the effects of LPS and the stimulatory effects of low levels of PMA, suggesting that phosphorylation was important in the actions of both LPS and PMA. The effects of LPS and of low levels of PMA were augmented by the protein kinase C (PKC) inhibitors H-7 (10-30 microM), staurosporine (2-10 nM) and calphostin C (0.1 microM). Higher concentrations of the inhibitors prevented LPS-evoked TNF release and its augmentation by low levels of PMA. However, they did not prevent the inhibition by high levels of PMA. One possible explanation for the results is that different isozymes of PKC may mediate the stimulatory as compared to the inhibitory effects of PKC on TNF production. PMID- 1628901 TI - Induction of differentiation of the human myeloid cell line, ML3, by tumour necrosis factor and interferon-gamma is accompanied by enhanced expression of the CD4 protein and messenger RNA. AB - Tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma) induce differentiation of human myeloid cell lines along the monocytic lineage. In this study we investigated the effects of TNF and IFN-gamma on the expression of the CD4 protein and messenger RNA (mRNA) in the two myeloid cell lines, ML3 and HL 60. We observed that CD4 antigen expression on ML3 cells is almost undetectable and that TNF and IFN-gamma induced CD4 antigen expression on these cells. HL-60 cells express surface CD4 antigen at high density and treatment with TNF and IFN gamma caused a decrease of CD4 expression. We also investigated the expression of CD4 mRNA in ML3 and HL-60 cells. ML3 constitutively express, albeit at low levels, CD4 mRNA. TNF induced CD4 mRNA in ML3 cells and IFN-gamma synergistically potentiated the effect of TNF, thus indicating that the enhanced expression of the CD4 protein on ML3 cells is due, at least in part, to an enhanced accumulation of the CD4 mRNA. CD4 mRNA is constitutively expressed in HL-60 cells at high levels. TNF and IFN-gamma, alone or in combination, did not cause any significant change of CD4 mRNA expression in HL-60 cells, thus indicating that decrease of surface CD4, which accompanies differentiation with these cytokines, is likely due to alterations of the CD4 protein synthesis and/or transport to the plasma membrane. These results provide evidence that myeloid cell lines are heterogeneous in expression of CD4, and that in ML3 cells, which constitutively express low levels of CD4 mRNA and undetectable amounts of surface CD4, the predominant effect of the two cytokines is to induce both CD4 mRNA and protein. PMID- 1628902 TI - Alveolar macrophages down-regulate local pulmonary immune responses against intratracheally administered T-cell-dependent, but not T-cell-independent antigens. AB - The role of alveolar macrophages in the pulmonary immune response against various antigens was studied after elimination of alveolar macrophages by intratracheal administration of liposome-encapsulated dichloromethylene diphosphanate. When the responses against T-cell-independent type 1 and type 2 antigens were compared, it was found that elimination of alveolar macrophages had no effect on T-cell independent antigens. Intratracheal antigen administration resulted in low lung associated, local responses, although some response was observed in the spleen. In contrast, elimination of alveolar macrophages resulted in an increase in local pulmonary immune response against T-cell-dependent antigens. We conclude from these experiments that alveolar macrophages play an important role in controlling the local pulmonary immune response against T-cell-dependent antigens by down regulation of local T-cell populations. The alveolar macrophages do not down regulate the response against intratracheally administered T-cell-independent antigens, although they are important in the protection against inflammatory damage caused by bacterial endotoxins. PMID- 1628904 TI - Molecular cloning, reconstruction and expression of the gene encoding the alpha chain of the bovine CD8--definition of three peptide regions conserved across species. AB - We report the cloning of a cDNA encoding the alpha-chain of the bovine CD8 (BoCD8 alpha). A bovine thymus cDNA library was hybridized at low stringency with a human CD8 alpha cDNA clone. The first round of screening of 5 x 10(4) independent colonies yielded 12 clones containing incomplete BoCD8 alpha genes. Two further rounds of colony hybridization were conducted, each using as a probe the 5' fragment from the longest BoCD8 alpha clone previously isolated. The final screening yielded a clone containing a 2 kilobase (kb) insert. We mapped and sequenced the 2 kb BoCD8 alpha clone and compared it with the published sequences of the genes encoding the human, mouse and rat CD8 alpha. Sequence analysis confirmed that the clone under study encoded the BoCD8 alpha. The overall similarity of the BoCD8 alpha coding region with the human CD8 alpha coding sequence is 74.7% at the nucleotide level and 62.1% at the protein level. Lower levels of similarity are found with the mouse and rat CD8 alpha. Interestingly, three separate highly homologous regions are clearly defined at the peptide level in bovine versus human and mouse versus rat comparisons. Two of the regions are highly conserved among all species analysed, while the most 5' region is not. We speculate that the latter region may contain the binding site of CD8 alpha to the alpha 3 domain of major histocompatibility complex (MHC) class I molecules. Sequence analysis showed that the 2 kb BoCD8 alpha clone contains an incomplete coding region, i.e. lacks six bases corresponding to the first two amino acids of the leader region. To allow efficient translation and processing of the BoCD8 alpha gene, we constructed a chimeric gene containing the coding sequence of the BoCD8 alpha clone and synthetic sequences corresponding to the first two amino acids of the human CD8 alpha leader sequence. The chimeric gene was subcloned in the pKSV10 expression vector. The pKSV10-BoCD8 alpha construct is efficiently expressed both transiently in COS cells and stably in L cells, as determined by Northern blot and by FACS analysis, using the ILA-51 monoclonal antibody to BoCD8 alpha. The latter result formally proves that the ILA-51 antibody does indeed recognize the product of the BoCD8 alpha gene, as previously suggested on serological grounds. PMID- 1628903 TI - Regulation of c-fgr messenger RNA levels in U937 cells treated with different modulating agents. AB - The U937 cell line was used to investigate the induction of messenger RNA (mRNA) for the c-fgr mRNA tyrosine kinase proto-oncogene in cells of the monocyte macrophage lineage. U937 cells were exposed to tumour necrosis factor-alpha (TNF alpha), TNF-beta and transforming growth factor-alpha (TGF-alpha), alone and in combination with PMA and 1,25-dihydroxycholecalciferol (1,25-DHCC). TNF-alpha and TNF-beta, but not TGF-alpha, decreased the proliferation of U937 cells in a time- and dose-dependent manner, and both TNF-alpha and TNF-beta enhanced the response of U937 cells to PMA during the first 24 hr of treatment and to 1,25-DHCC over 72 hr. TNF-alpha induced a rapid increase in c-fgr mRNA levels within 4 hr, in contrast to slower induction by PMA and 1,25-DHCC. TNF-alpha and 1,25-DHCC together had an additive effect on c-fgr mRNA levels. In U937 cells exposed to PMA, c-fgr mRNA levels continued to increase over 72 hr. Levels of c-fgr mRNA induced by the various modulating agents did not correlate clearly with the changes in proliferation. Therefore, we suggest that although the c-fgr gene product may have a role in differentiation, the more significant role is likely to be in the fully differentiated macrophage. PMID- 1628905 TI - Technology assessment of periodic health examinations for school children in Japan. AB - In Japan, preventive health services have been heavily concentrated in mass screening. This prioritization is also true in the field of school health. Annual mass health screenings have been provided to 21.3 million children from kindergarten to university level under the School Health Law. In 1973, periodic health examinations were extended to include screenings for renal and heart diseases. This extensive screening program has been introduced without any evidence supporting its effectiveness. Although available data relative to these screenings in Japan were examined, neither the efficacy of the tests nor the effectiveness of the screenings were observed. Moreover, costs for the tests during the initial phase amounted to US $120 million and $65 million, respectively. PMID- 1628906 TI - Cost-effectiveness of misoprostol in Sweden. AB - Based on an American multicenter study, an economic evaluation of prophylactic misoprostol was undertaken in Sweden. The study included 420 patients with osteoarthritis and nonsteroidal anti-inflammatory drug (NSAID)-associated abdominal pain, but no gastric ulcer at inclusion. The frequency of ulcer development with and without prophylactic misoprostol was assessed at 21.7% and 5.6%, respectively, for a 3-month period. All costs for drugs, ambulatory care, hospital care, loss of production, as well as other factors such as dosage and compliance, were transferred to Swedish conditions. It was concluded that in patients with osteoarthritis and NSAID-induced abdominal pain, prophylaxis with misoprostol is cost-effective in Sweden, which is similar to what is found for other countries. A prerequisite for this result is a frequency of ulcer development of 15%. A patient compliance to prophylactic treatment of more than 60% is also presupposed (79% was observed in the above study). Due to the high age of the osteoarthritis patient population, the cost-effectiveness is influenced to only a minor extent by whether indirect costs are included in the calculation. PMID- 1628908 TI - Health care technology transfer in Latin America and the Caribbean. AB - The greatest problem concerning health care technology for developing countries is that they are dependent upon the industrialized world for technology. The only short-term solution to this problem is to improve the choices that are available to them. This goal will require changes in the structure and processes of policy making. A particular difficulty for these countries is the lack of trained personnel in fields related to technology assessment. PMID- 1628907 TI - Nonexperimental evaluation of the effectiveness of a screening program for lung cancer. AB - The effectiveness of screening to control lung cancer was examined in the German Democratic Republic by analyzing data from a cancer registry and incidence and mortality rates for lung cancer relative to different screening policies, and by two case-control studies. Mortality from lung cancer did not appear to be affected by the screening programs studied. The high cost of mass screening, combined with uncertainty about the benefits of early treatment of lung cancer, outweigh the vague advantages of such screening. PMID- 1628909 TI - Organizing for cancer control. The diffusion of a dynamic innovation in a community cancer network. AB - This paper examines the diffusion of a "dynamic" innovation--research on the prevention and control of cancer--in a community cancer network. By analyzing the social structures and communication strategies of network members, as well as the attributes of the innovation, the authors explain why this innovation is diffusing more slowly than its "formed" counterpart--research on the treatment of cancer. PMID- 1628910 TI - The technology assessment and practice guidelines forum. A modified group judgment method. AB - This article describes a new group-judgment process, modified from the consensus development approach of the U.S. National Institutes of Health. It is called the "forum" method, a shorthand term for "technology assessment and practice guidelines forum." This approach is aimed at (a) describing the current state of knowledge of the technology under study; (b) developing practice guidelines for the use of the technology; and (c) providing information for insurers, consumers, policymakers, and others. A pilot study was conducted focusing on total parenteral nutrition. The validity of the process and of the recommendations and their acceptability were evaluated in a survey of participants and a selected group of nonparticipants. Based on the survey results, the forum method appears to be a valuable method for assessing technologies, defining their clinical role, and developing practice guidelines. PMID- 1628911 TI - Magnetic resonance imaging. Diffusion of technology in an ambulatory setting. AB - To better understand technology diffusion in an ambulatory care setting, we analyzed adult outpatients' use of magnetic resonance (MR) and computed tomography (CT) imaging in a group-model HMO between 1986 and 1989. The use of MR, but not CT, increased at a rapid pace with only a small proportion of the scans being accounted for by primary care physicians. PMID- 1628912 TI - An experimental ward. Improving care and learning. AB - The rapidly changing health care system is still largely organized according to old, and increasingly outdated models. The contemporary demands of patient care and residency training call for an experimental ward, which can develop and test new techniques in hospital organization and the delivery of care in a comprehensive way. PMID- 1628913 TI - Progress on firms research. AB - Firms research combines parallel providers of care, ongoing patient randomization, and continuous experimental changes and improvement. This form of efficient research now has a substantial track record of published studies by a growing number of hospitals. PMID- 1628914 TI - The Cleveland Veterans Affairs Medical Center firm system. AB - Hospital-based "firms" provide a means for combatting the fragmentation experienced by both patients and caregivers in the modern teaching hospital environment. A "firm" is an academic group practice that includes attending physicians, physician trainees, nurses, other staff, and patients. Each person's relationship with a firm lasts throughout his or her association with a particular institution. This article describes the firm system that was recently implemented on the Medical Service of the Cleveland VAMC. This system incorporates both inpatient and outpatient general medical services and provides for unbiased assignment of patients, physicians, and nurses. PMID- 1628915 TI - It's time to rethink health care technology assessment. AB - Health care technology assessment is broadly and ambiguously interpreted, diluting its role. It is time to recast the field. We must elucidate it in the contemporary context of health inquiry, explicitly relating it to such pursuits as quality assurance, health services research, effectiveness research, medical informatics, and technological innovation. PMID- 1628917 TI - Report from the British Columbia Office of Health Technology Assessment (BCOHTA). Workplan of the office. PMID- 1628916 TI - On the discounting of gained life-years in cost-effectiveness analysis. AB - A controversial issue in cost-effectiveness analysis is the discounting of gained life-years. What has not been realized, however, is that the different methods used for discounting this measurement provide fundamentally different results. The method used is seldom explicitly stated. In the present article the four main methods for the discounting of gained life-years are reviewed and compared. The conclusion is that if we wish to continue comparing results, researchers must employ the same methodology. PMID- 1628918 TI - Report from the Conseil d'Evaluation des Technologies de la Sante (CETS). Mandate of the conseil. PMID- 1628919 TI - Report from the Canadian Coordinating Office for Health Technology Assessment (CCOHTA). Experimental drug policies in Canada. PMID- 1628920 TI - Report from the Health Council of The Netherlands. Heart transplants: from recommendation to report. PMID- 1628921 TI - Report from the U.S. Institute of Medicine (IOM). The artificial heart: prototypes, policies, and patients. PMID- 1628922 TI - [Bradycardic arrhythmias]. PMID- 1628923 TI - [The effect of extensive surgical intervention on cellular immune response]. PMID- 1628924 TI - [Assessment of the preoperative risk of existing lung diseases]. PMID- 1628925 TI - [Perioperative management of the diabetic patient]. PMID- 1628927 TI - [Perioperative anesthesiologic management]. PMID- 1628926 TI - [Gastrointestinal diseases in perioperative risk assessment]. PMID- 1628928 TI - [Chemotherapeutic prevention of infection in invasive interventions in high-risk internal medicine patients]. PMID- 1628929 TI - [Postoperative neuropsychiatric disorders and transitory syndromes]. PMID- 1628930 TI - [Painless macrohematuria]. PMID- 1628931 TI - [Unusual clinical manifestation of lymphangiosis carcinomatosa of the lungs]. PMID- 1628933 TI - Toluidine blue staining and early detection of oral precancerous and malignant lesions. PMID- 1628932 TI - Chronic mucositis. PMID- 1628934 TI - What is the optimal treatment for mild/moderate hypertension? PMID- 1628935 TI - Tuberculosis elimination in Europe. PMID- 1628936 TI - Good communication is good medicine. PMID- 1628937 TI - Transoesophageal echocardiography--widening the scope. PMID- 1628938 TI - The extensor plantar response. PMID- 1628939 TI - Childhood leukaemia in Ireland. AB - In response to professional and public concern about health consequences, in particular cancer risk, from previous and current levels of ionising radiation in the Irish Sea, a study of incidence and mortality from acute lymphoid leukaemia (ALL) and other lymphoid malignancies in children was undertaken. Overall rates were similar to those found in other western populations and distribution of high rates was quite random over the country as a whole. There was a small but significant excess in incidence of ALL for the years 1974-76 in a narrow three mile wide strip along the east coast. It is not possible in the context of this study to postulate aetiological factors which might explain this finding. PMID- 1628941 TI - Changing characteristics of Irish menopausal women seeking assistance. AB - In the two years since its inception 425 patients have been seen at the Menopause Clinic. Audit of the first 100 women attending against 100 first seen one year later have revealed some significant differences in referral patterns. The earlier group were likely to have significantly more social problems whereas in the latter, more were likely to show concern for osteoporosis or need modification of ongoing treatment. PMID- 1628940 TI - An explanation for the difference in general practitioner consultation rates between GMS and non-GMS patients. AB - This study compares annual consultation rates between 3,111 General Medical Services and private patients, and their family doctors in three large general practices in Dublin. Visiting rates were substantially different between practices and between GMS and private patients. However, GMS patients were older and had 50% more chronic illnesses. When the effects of age and illness were controlled in a multiple regression model, GMS status accounted for less than 5% of the variation in visiting rates. GMS patients consult their practitioners in proportion to their medical need. PMID- 1628942 TI - DES clinic--the first six months. AB - In October 1990 a DES (Diethylstilbestrol) clinic was established at the National Maternity Hospital, Dublin. We describe the results of the first six months of the clinic. During this time, 172 inquiries were received; 95 women were seen at the clinic, 16 were deemed to be DES--exposed and eight were classified as possibly DES exposed. Classical cervicovaginal signs of DES exposure were noted in 15 women, a further eight women showed cervical epithelial abnormalities at colposcopy, the history of in utero DES exposure was confirmed in eight cases. No cases of cervical intraepithelial neoplasia or vaginal clear-cell adenocarcinoma were detected. Pregnancy related problems possibly attributable to DES exposure were documented in six women. PMID- 1628943 TI - Changing trends in approach to wheezy children by family doctors. AB - The prevalence of asthma in children appears to have increased dramatically over the past 20 years. There is evidence that some of this increase is due to earlier recognition and relabeling of symptoms such as wheeze. In this study we set out to see if increased awareness of the presentation of asthma in young children has led to earlier diagnosis by family doctors and a decrease in the number of courses of antibiotics given before the introduction of bronchodilators. The family doctor records of 769 children aged 0-5 years were examined retrospectively by an independent paediatrician. One third had at least one documented episode of wheeze and the prevalence of asthma was 10.5%. The mean age of diagnosis was 2.59 years although the mean age at which bronchodilators were introduced was 2.22 years. 22 children, who were never recorded as being asthmatic, were nevertheless appropriately treated with bronchodilators. PMID- 1628944 TI - Early experience with pre-deposit autotransfusion in elective orthopaedic surgery. AB - Pre-deposit autotransfusion has been shown to be an effective method of providing blood for planned surgery. This study discusses preliminary experience with pre deposit autotransfusion an alternative to homologous blood from those patients considered suitable donors according to established guidelines. In the first 24 weeks, 31 patients pre-donated 59 units of autologous blood for planned surgery. Twenty-nine patients (94%) underwent surgery and 24 (83%) of these did not require additional homologous blood. Two donations (3.6%) were complicated by minor reaction. All donors expressed satisfaction with the service. The authors conclude that in elective orthopaedic surgery pre-deposit autotransfusion is a safe and effective alternative to homologous transfusion. PMID- 1628945 TI - An Irish out-patient based in-vitro fertilisation service. AB - The first year's activity of a fully out-patient based, self financing, in vitro fertilisation service is reported. 98 couples had superovulation regimes tailored to need. 138 cycles were started. 109 retrievals were attempted using the vaginal ultrasound probe under Fentanyl and Midazolam sedation. In 106, oocytes were successfully retrieved (average seven per patient). In 80, embryos were transferred (average three). 13 patients achieved clinical pregnancies giving an overall pregnancy rate of 9.4% per cycle, 12% per oocyte retrieval, 16.5% per embryo transfer and 13% per patient who embarked on the programme. One pregnancy was ectopic, two aborted, and 10 are ongoing; this includes seven singleton foetuses and three sets of twins. All pregnant patients were referred back to their unit of origin for antenatal care and delivery. PMID- 1628946 TI - Lyme disease in Ireland. AB - The data pertaining to Irish specimens sent to the Lyme disease Laboratory at Charing Cross Hospital since 1986 is presented and discussed. In the period up to June 1990, 484 specimens were tested, 14% of these were positive by enzyme linked immunosorbent assay or indirect immunofluorescent assay. Only 13 of these were confirmed as positive by immunoblotting. PMID- 1628947 TI - Growth hormone therapy in Turner's syndrome. AB - Girls with Turner's Syndrome respond to growth hormone therapy. In combination with anabolic steroids, studies show a synergistic effect that does not cause an undue increase in bone age. As studies progress, patients are growing taller than their predicted final heights. Whether the increase in linear growth velocity will be sufficient to bring the Turner's Syndrome patient in to the normal range (greater than 150cms) and remove short stature as a necessary stigma for these unfortunate patients remains to be seen. PMID- 1628948 TI - Duodenal rupture with avulsion of the bile duct: an unusual injury. AB - Blunt abdominal trauma may give rise to infrequent and unusual patterns of organ damage requiring prompt and complete exploratory laparotomy if the full extent of injury is to be recognised. We present a case of avulsion of the common bile duct in association with duodenal rupture to illustrate the importance of this strategy. PMID- 1628949 TI - Mammographic needle localisation of impalpable breast lesions. AB - Refinements in mammography have led to an increased number of needle localised breast biopsies for impalpable breast lesions. This paper review 139 needle guided biopsies from June 1986 to December 1990 in 132 patients. Forty four patients (32%) biopsied had malignant lesions the vast majority (91%) of which were reported as either non-invasive or invasive less than 2 cm in diameter. Fourteen patients in this group had ductal carcinoma in-situ. When compared with 100 consecutive palpable breast carcinomas during the same period, needle localised biopsies had a higher proportion of non-invasive lesions and fewer were associated with lymph node involvement. Needle guided breast biopsy detects carcinoma at an earlier stage and may reduce morbidity and mortality from breast cancer. PMID- 1628950 TI - A survey of rugby injuries attending an accident & emergency department. AB - A prospective study was carried out on 242 patients attending an Accident & Emergency Department with injuries sustained while playing rugby football. The average age was 19.8 years. Head and neck injuries were more prevalent but less serious then in studies carried out before recent law changes. The lower limb was still the part of the body most frequently injured but again there were fewer serious injuries. There was a marked increase in upper limb injuries. Wing forward was the position most likely to give rise to injuries and prop was the least. Poor compliance is still a significant problem with rugby injuries can only lead to an improvement in the safety of the game. PMID- 1628951 TI - Trichobezoar--a condition to think of in case of mobile abdominal mass. AB - A twenty year old girl was referred to the surgical out-patients clinic with a history of intermittent epigastric pain and vomiting of five months duration. The patient enjoyed good health prior to this and her past medical history was uneventful. Findings on physical examination included pallor, patchy alopecia and a soft mobile, non-tender mass in the epigastrium and left upper quadrant of the abdomen. When questioned she admitted to a history of trichophagia for as long as she could recall. A provisional diagnosis of gastric trichobezoar was made. Radiological investigations included an abdominal ultrasound which showed a large ill-defined mass lesion with poor transonic features, situated in the upper abdomen and extending from the left upper quadrant across the midline to the liver margin. Barium meal revealed that the greater part of the lumen of stomach was occupied with material of an indeterminate nature. Her haematological investigations showed Haemoglobin 9.5 gm/dl and Leucocyte Count 9.0 x 10(9)/L. Her Urea and Electrolytes were within normal range. At laparotomy a large hair ball extending from the Stomach into the duodenum and proximal jejunum was removed through a vertical gastrotomy incision. The patient had a satisfactory post-operative convalescence and was discharged two weeks later. PMID- 1628952 TI - Promoting health. PMID- 1628953 TI - Comparison of the ease of handling of four different drug dispenser types in rheumatoid arthritis. PMID- 1628954 TI - A cluster of diaphragmatic hernias! Where to now? PMID- 1628955 TI - Renal haemangioma complicated by a fatal hepatic bleed. PMID- 1628956 TI - Irish Heart Foundation nutrition policy. PMID- 1628957 TI - Headache responses following m-chlorophenylpiperazine in bulimics and controls. AB - We have previously reported that the serotonin (5-HT) agonist meta chlorophenylpiperazine (m-CPP) induced late occurring migraine-like headaches in a group of patients with eating disorders and controls (n = 52). In this report, we extend our analyses of these data and describe results indicating that headache responses following m-CPP are greater in patients with bulimia nervosa than controls, regardless of the presence of anorexia nervosa or major depression. Although patients with severe migraine-like headaches had higher peak m-CPP levels than patients without severe headaches, these levels are not higher than other groups studied who did not get headaches. These findings suggest that post-synaptic 5-HT receptor sensitivity is altered in the vascular tissues of bulimic patients. Additional disturbances in 5-HT function, perhaps presynaptic ones, may be associated with anorexia nervosa and major depression. Similar alterations in other 5-HT pathways at or above the level of the hypothalamus may contribute to binge eating and other behavioral symptoms of bulimia nervosa. Further studies exploring the functional integrity of 5-HT receptors and their subtypes are warranted in bulimic patients, as well as in patients with nonbulimic anorexia nervosa, minor and major depression without an eating disorder, and migraine and other headache patients. PMID- 1628958 TI - Medication use and disability among migraineurs: a national probability sample survey. AB - OBJECTIVE: To measure the use of prescription medication in treating migraine headache and the associations between medication use and sociodemographic factors, and headache characteristics. DESIGN: National sample survey using a mailed questionnaire to determine symptoms accompanying or preceding severe headaches; frequency, duration, and disability from severe attacks: use of medications to control pain; and medical-care use for severe headaches. SETTING: A stratified sample of United States households. PATIENTS: A sample of 20,468 respondents, aged 12 to 80 years, who responded to a survey on "severe" headaches during the prior year. MEASUREMENTS AND MAIN RESULTS: Overall, 20.2% of respondents reported severe headaches. Migraine was found in 17.6% of females and 5.7% of males. Of the migraineurs, 40.1% of female and 28.3% of male migraineurs reported using prescription drugs to control pain. Blacks were less likely than whites to report prescription use. Insignificant differences were seen in rates of prescription use among various income levels and regions of the country. Use of prescription medication varied considerably by symptoms and characteristics of migraine attacks. Vomiting and sensory aura were most frequently associated with medication use, as were severity and duration of attacks. Use of urgent-care services for severe headache attacks was associated with frequent use of prescription medications. Patients who reported a physician diagnosis of migraine were more likely to use prescription medication than other migraineurs. CONCLUSIONS: Most migraineurs in the United States are not being treated with prescription medications. Many active migraine patients would benefit from appropriate treatment if care was sought and diagnosis made. PMID- 1628959 TI - Platelet gamma-aminobutyric acid levels in migraine and tension-type headache. AB - Gamma-aminobutyric acid (GABA) levels in platelets were measured in 19 patients with migraine (7 males and 12 females, average age: 36.5 years) and 27 patients with chronic tension-type headache (TH; 9 males and 18 females, average age: 48.9 years). Twenty-one normal healthy volunteers composed the control group (11 males and 10 females, average age 34.9 years). The GABA levels in platelets were determined using high performance liquid chromatography with fluorescent detection (HPLC-FC). The GABA levels in platelets were 30.8 +/- 11.7 pmol/10(9) platelets (mean +/- S.D.) in the patients with migraine, 43.1 +/- 11.8 pmol/10(9) platelets in the patients with TH and 34.7 +/- 8.1 pmol/10(9) platelets in the healthy controls. The platelet GABA levels in the patients with TH were significantly higher than in the migraine patients and the healthy controls (p less than 0.05). The possible role of GABA in headache is discussed. We consider that TH may be a state of neuronal hyperexcitability similar to migraine and that GABA in the platelets of patients during TH attacks may be elevated to counterbalance it. Alternatively, we suggest that the rise of GABA levels in platelets is related to emotional factors, such as depression, in the TH patients. Further studies must be undertaken concerning the relationship between platelet GABA levels and headache. PMID- 1628960 TI - Olfaction in migraineurs. AB - Many investigators have described olfactory dysfunction among migraineurs. Olfactory stimuli can precipitate migraine, and olfactory hallucinations can occur as auras of migraines or as part of the symptom complex. Despite many reports linking olfactory phenomena and migraine, no evaluations of the olfactory abilities of migraineurs have been documented. To begin such assessments, sixty seven consecutive migraine patients were given Pyridine odor threshold tests. Twelve of them (18%) scored as hyposmic or anosmic. In comparison, 1% of the general population of the U.S. is hyposmic or anosmic. Aside from possible diagnostic or methodological error, several possibilities may account for our result: migraine may induce olfactory pathology; olfactory pathology may induce migraine, or; a common pathogen may induce both olfactory dysfunction and migraine. The association of migraine with the emotional component of the limbic system has long been recognized, and our results strengthen its association with the olfactory component as well. Headache patients should be tested for olfactory loss and warned of such risks as inability to detect gas leaks and spoiled food. PMID- 1628961 TI - Hemicrania continua: attacks may alternate sides. AB - Hemicrania continua (HC) is characterized by a continuous unilateral headache of moderate severity, occurring in 2 patterns; a continuous form in which headaches persist continuously without remission for years, and a remitting form, consisting of headache phases separated by periods of pain-free remission. The remitting form of HC must be distinguished from other cyclical headache disorders such as episodic paroxysmal hemicrania and episodic cluster headache. Characteristically, the headache of HC is unilateral and without sideshift. We now report a case of HC in which headaches alternate sides. PMID- 1628962 TI - Psychometric characteristics of the Headache-Specific Locus of Control scale. AB - Martin and colleagues have described their development of a Headache-Specific Locus of Control scale (HSLC) which contains 11 items for each of its three subscales: internal, health care professional, and chance orientations. In this replication study, we gathered data from patients who came to a Headache Clinic in a medical center (n = 151) and from a comparison sample (n = 192). Factor analysis and alpha coefficients were similar to those reported by Martin. Only small correlations were found between the subscale scores although some of them were statistically significant. This suggests that the HSLC is a psychometrically competent instrument. Additionally, mean scores of its three subscales differentiated the patient population from those whose headaches were less severe and thus did not seek help. PMID- 1628963 TI - More on mCPP and migraine. PMID- 1628964 TI - [Regulation of the epidermal permeability barrier by lipids and hyperproliferation]. AB - The stratum corneum, the permeability barrier between the internal and external milieu, is composed of protein-enriched cells and lipid-enriched intercellular domains. Lipid synthesis is localized in the keratinocytes. The lamellar bodies located in the keratinocytes secrete lipids (sphingolipids, free fatty acids and cholesterol) into in the intercellular spaces of the stratum corneum. A disturbance of barrier function results in an increase in the synthesis of free fatty acids, non-saponified lipids and cholesterol in all nucleated layers of the epidermis. Cholesterol synthesis is regulated by the enzyme HMG-CoA reductase. After acute disturbance of barrier function by acetone treatment the increase in cholesterol synthesis occurs mainly in the lower epidermis (stratum basale/stratum spinosum), while after chronic disturbance by a diet deficient in essential fatty acids the increase shifts to the upper epidermis (stratum granulosum). After barrier disturbance not only lipid but also DNA synthesis is stimulated. Stimulation of DNA synthesis leading to epidermal hyperplasia may be a second mechanism by which the epidermis tries to correct defects in barrier function. Artificial barrier repair with latex occlusion prevents an increase in lipid and in DNA synthesis. Chronic barrier impairment by topical application of lovastatin, an inhibitor of cholesterol synthesis, or by a diet deficient in essential fatty acid also leads to an increase in lipid and DNA synthesis and to epidermal hyperplasia. Epidermal lipid and DNA synthesis in essential fatty acid deficiency is independent of prostaglandin E2, but depends on n-6-unsaturated fatty acids such as linoleic and columbinic acid. PMID- 1628965 TI - [Toxic oil syndrome--an example of an exogenously-induced autoimmune disease]. AB - In 1981 epidemic poisoning with adulterated cooking oil occurred in Spain, affecting more than 20,000 people. The condition caused has since become known as the toxic oil syndrome (TOS). About 10-15% of the patients with acute symptoms developed a chronic disease with scleroderma-like skin manifestations, polyneuropathy and myositis. While the acute phase of the TOS was characterized by eosinophilia and elevated IgE, the chronic stage involved humoral autoimmune phenomena, such as antinuclear and antinucleolar antibodies, in many cases. In women with the chronic phase of TOS there was a possible prevalence of HLA-DR3 and HLA-DR4. The recently characterized eosinophilia-myalgia syndrome (EMS), which is thought to have been induced by contaminated L-tryptophan preparations, is similar to the TOS in some particulars. Understanding of the toxicological, immunological and genetic pathways leading to these diseases might give us some insight into the pathogenesis of spontaneously occurring autoimmune diseases, such as systemic scleroderma. PMID- 1628966 TI - [The effect of UV-A and UV-B irradiation on the skin barrier. Skin physiologic, electron microscopy and lipid biochemistry studies]. AB - In order to gain insight into the effects of UV-irradiation on the skin barrier, functional (skin reactivity), electron microscopic and lipid-biochemical studies were performed. In three different irritation models, both UV-A-irradiated and UV B-irradiated areas proved to be more resistant to damage than normal skin, providing evidence for improvement of barrier function after UV irradiation. Electron microscopic evaluation showed that UV-B induced a significant increase in horny cell layers, whereas after UV-A no change was detected. However, both UV B and UV-A exposure resulted in an increase in the amount of all stratum corneum lipids. This was also observed in all major ceramide subfractions, which are believed to be the essential lipid constituents for the epidermal barrier function. These findings may explain the known beneficial effects of phototherapy in dermatoses with impaired barrier function, i.e., atopic dermatitis. PMID- 1628967 TI - [Local and systemic humoral immune response to protein I of Neisseria gonorrhoeae]. AB - Knowledge of the immune response to natural infection with Neisseria gonorrhoeae is presupposition for the development of a gonococcal vaccine. Pili and protein I have gained importance for a subunite vaccine. A pilus vaccine proved to be ineffective in a field trial due to extensive pilus variability. According to an alternative strategy protein I may represent an important vaccine candidate for a gonococcal vaccine. To study the local and systemic, humoral immune response to N. gonorrhoeae cervical secretion, vaginal fluid and serum from prostitutes and family planning patients were compared by the use of a protein I ELISA. In local secretions and in serum patients in the study group showed significantly higher anti-protein-I-IgA-levels than patients in the control group. In cervical secretion immune response to an acute gonococcal infection consisted of a short lived, significant increase of anti-protein-I-IgA, while anti-protein-I-IgG showed a lower, but longer lasting significant increase. The course of the immune response in vaginal fluid reflected the immune response of cervical secretion at a lower level. In serum antigenic stimulus of a local gonococcal infection resulted in a significant but short lived protein I specific IgG immune response. In local infection with N. gonorrhoeae protein I represents a target antigen of the local and systemic immune response. Clear differences exist between local and systemic humoral immune response in the protein I reactive immunoglobulin class and in the course of reactivity. In the future it may be possible to define epitopes on protein I which induce protective immunity. PMID- 1628968 TI - [Ross syndrome]. AB - We report on a 25-year-old patient with hyporeflexia, progressive segmental hypohidrosis and dry, scaly skin mimicking tinea manuum on the affected palm. This case is the fourth with Ross syndrome and skin manifestations as a result of segmental hypohidrosis. PMID- 1628969 TI - [Mycobacterium kansasii seroma of the skin in HIV infection]. AB - We report on an HIV-infected patient with AIDS in whom a smoothly demarcated area of resistance in the size of a fist was found on the inside of the thigh. Investigation by sonography for clinical differential diagnosis confirmed that a haematoma, a seroma or an abscess might be present. Upon puncture of the cavity, serous exudate was obtained. The microbiological investigation resulted in the growth of Mycobacterium kansasii. The detection of this agent in throat and sputum samples from the patient and the occurrence of an osteomyelitis lesion at the same time indicate that the seroma was a partial manifestation of a disseminated Mycobacterium kansasii infection. No indications of a transcutaneous route of infection was found. Upon antimicrobial chemotherapy after the determination of resistance the seroma disappeared. PMID- 1628970 TI - [Perforating cutaneous amyloidosis]. AB - Two patients, a 79-year-old man suffering from familial lichen amyloidosus and a 44-year-old women with biphasic cutaneous amyloidosis, developed small, centrally ulcerated papules. Histological and ultrastructural examination confirmed transepidermal elimination of amyloid. In contrast to other transepidermal elimination diseases, the material eliminated in perforating cutaneous amyloidosis is of epidermal origin. PMID- 1628971 TI - [Dowling-Degos disease with exclusively genital manifestations]. AB - We report on two women with pigmented lesions of the vulva. The histopathology (filiform downgrowth of pigmented epithelial strands two to four cells wide, extending from the interfollicular epidermis and from follicular infundibula; no increased numbers of melanocytes; horn pseudocysts) was specific for Dowling Degos disease. One patient also had acne inversa, and the other patient had been treated surgically for a pilonidal sinus some years before. The spectrum of conditions that should be considered in the differential diagnosis of genital pigmented lesions is discussed. Vulvar melanosis, genital lentigo, malignant melanoma, acanthosis nigricans maligna and benigna and syndromes occurring concomitantly with pigmentation of the mucosa need to be excluded. The association of Dowling-Degos disease with acne inversa, which was recently described for the first time, is discussed. PMID- 1628972 TI - [Bowenoid actinic keratosis: therapy with intralesional injection of recombinant beta-interferon]. AB - Biopsy-proven bowenoid actinic keratosis located in the pretibial region in each of two elderly women (61 and 81 years) were treated with intralesional injections with a new recombinant beta-interferon. The treatment took the form of intralesional injections three times a week over 3 consecutive weeks. The dose per single injection was 1.5 or 1.0 MU interferon, respectively. Clinical and histological examinations showed a complete response in both patients. Controls up to 18 months showed no relapse. There were no flu-like side-effects. Leukocyte counts decreased by 2700 and 500 cells per microliter during therapy. PMID- 1628973 TI - [Sneddon syndrome with detection of anti-phospholipid antibodies]. AB - The association of livedo racemosa and neurological lesions is described as Sneddon's syndrome. A 48-year-old woman with Sneddon's syndrome accompanied by antiphospholipid antibodies is presented. PMID- 1628974 TI - [Onset of disseminated Bloch-Sulzberger incontinentia pigmenti]. AB - The case report of a 2-week-old girl suffering from incontinentia pigmenti (Bloch Sulzberger Syndrome) with disseminated urticarial erythemas, papules and vesicles at the onset is presented. Histological examination showed eosinophilic spongiosis. The peripheral blood eosinophilia and the development of typical lesions led to the diagnosis of incontinentia pigmenti. Eosinophilic spongiosis and peripheral blood eosinophilia are important symptoms in the diagnosis of atypical incontinentia pigmenti. PMID- 1628975 TI - [Transmission of infectious dermatoses by hand towels and soaps]. PMID- 1628976 TI - [Resochin in HIV infection]. PMID- 1628977 TI - [The tree, from which chrysarobin was isolated]. PMID- 1628978 TI - [The First Bruno Bloch Memorial Lecture]. PMID- 1628979 TI - [Sun protection]. PMID- 1628980 TI - The relationship of personal values to concerns about radioactive waste transport. PMID- 1628981 TI - Experimental release of 131I: the Green Run. AB - In December 1949, a large amount of 131I was released to the air at Hanford during the dissolving of irradiated uranium fuel for a classified military experiment called the "Green Run." Reports of the release have varied from about 0.15-0.3 PBq. Using, as a guide, the reported measurements of 133Xe released during the experiment, the amount of 131I released has been reanalyzed. The results indicate that about 0.40 +/- 0.12 PBq (11 +/- 3 kCi) was released, somewhat larger than the largest previous estimates. PMID- 1628982 TI - Area and time distribution of external and internal doses from Chernobyl fallout: the lack of correlation in Norway. AB - Population doses from external radiation and internal food-based radioactivity were calculated each month for each municipality for 3 y immediately following the Chernobyl contamination in Norway. The main polluted regions are sparsely populated but comprise important food production areas. The external dose data base was calculated based on fallout deposition and measurements in dwellings, whereas the totally independent internal dose data base was calculated on a large number of food measurements and knowledge of both the food distribution system and the countermeasures taken. The internal dose in the densely populated municipalities was comparably higher than expected from local deposition, despite the fact that countermeasures had some effect. Thus, the correlation between internal and external dose for individual municipalities is rather weak. This study shows that a traditional deposition/transfer factor approach may be inappropriate if used in countries with large variation in population density and agricultural ecosystems and in combination with effective countermeasures. PMID- 1628983 TI - In-situ determination of deposited radionuclide activities: improved method using derived depth distributions from the measured photon spectra. AB - When applying the standard method of in-situ gamma spectrometry to determine deposited radionuclide activities, an assumption is needed regarding the depth distribution of radionuclides in the ground. The method can be improved by assessing, from information contained in the spectrum, the attenuation of the radiation by the soil and vegetation. By comparing the count rates of the x ray and the gamma-ray lines of its daughter nuclide 137mBa, the 137Cs activity per area can be determined. The range of applicability of the method is discussed by means of an uncertainty analysis, and the method is applied to post-Chernobyl measurements. A comparison with the results of the standard method of in-situ spectrometry demonstrates the progress achieved by the proposed method. Nevertheless, the method still has some shortcomings for the peak analysis that could be improved by better detector resolution or better computer software. PMID- 1628984 TI - Radioactivity in size-separated municipal incinerator ashes. AB - Radionuclide concentrations of the 238U- and 232Th-decay series, as well as 40K and 137Cs, were determined in size-separated fly ashes and bottom ashes from two municipal incinerators. Secular equilibrium was observed for several of the series' radionuclides, though 222Rn losses during combustion were evident. The fly-ash samples showed increasing enrichment of 40K, 137Cs, and 210Pb as particle diameters decreased, due to their volatility and subsequent condensation, and typically contained higher activities of these volatile radionuclides. Radon emanation from the bottom ashes was not detected but the fly ashes had an emanting power near 7%. Only 40K and 137Cs were found to be water-soluble, with significantly greater solubilities occurring for the fly ashes. Overall concentrations suggest that municipal incinerator ashes contain the equivalent radioactivity of surface soil and substantially less than ashes from coal combustion. It is shown that an incinerator's contribution to the atmospheric radionuclide burden is minimal and, from a radiological viewpoint, their residual ashes can be safely used in construction materials. PMID- 1628985 TI - Preparation of a 99mTc wipe standard for survey instrument calibration in nuclear medicine. AB - A method was developed for the preparation of a standard source to satisfy the U.S. Nuclear Regulatory Commission requirement for calibration of wipe-assay procedures used in nuclear medicine laboratories. An essential element of this standard was that a locally prepared calibration wipe could be used with thin window Geiger-Muller detectors that detect 99mTc conversion electrons with high sensitivity. This proposed calibration wipe was evaluated with both a NaI(Tl) well counter and a thin-window Geiger-Muller pancake probe. Average detector sensitivities of 1,540 and 160 counts min-1 per 2000 disintegrations min-1, respectively, were found for 99mTc. An analysis of the errors for each step of the procedure showed most to be less than 3% (95% confidence level). The nuclear medicine dose calibrator, used to assay the activity from which the wipe was prepared, was estimated to contribute a 9% absolute calibration error. Use of the pancake probe contributed a 12% geometry-reproducibility error. The total error associated with the use of the calibration wipe standard to calibrate a typical 99mTc wipe-assay procedure, exclusive of the count-dependent error associated with the number of counts acquired, was found for the NaI(Tl) well counter to be given by a percentage of 2 SD = 10% and for the thin-window Geiger-Muller pancake probe, percentage 2 SD = 16%. Coating of the calibration wipe with an acrylic spray, to prevent it from contaminating instruments during use, was evaluated. This coating was effective while it reduced the detectability of the wipe activity by a negligible degree. PMID- 1628986 TI - Reducing transmitted radiation in dental radiography. AB - A significant amount of radiation escapes the rear of an image receptor in conventional dental radiographic procedures despite the placement of a lead containing backing at the rear of the film pack. The purpose of this investigation was to place additional layers of lead on the film pack in an attempt to reduce transmitted radiation to tissues behind the film. Reduction of dose to tissues behind the film causes a reduction in scatter radiation to critical organs such as the thyroid gland and salivary glands. A thermoluminescent lithium fluoride dosimetry system (TLD) was used and calibrated in both the beam of interest and tissue of interest. A tissue-equivalent anthropomorphic phantom was used for dose determination. Successive layers of lead foils were added to the image receptor, and dose was determined for each additional lead foil in the tissues behind the image receptor. Two sets of exposure conditions were used, namely: 70 kVp, 10 mA, and 0.6 s, and 90 kVp, 10 mA, and 0.6 s. The beam-film-patient orientation used was for a first molar bitewing radiographic projection. Four lead layers (three additional foils equalling 3.92 x 10(-3) mm of lead) on the conventional film package resulted in a significant dose reduction. Four layers of lead resulted in a dose less than one-third that of the conventionally shielded package. PMID- 1628987 TI - Long-term retention of 210Pb in man: a unique case of internal contamination. AB - Knowledge of the long-term effective half-life of 210Pb in man is essential for estimating the cumulative exposure to inhaled short-lived radon daughters from measured values of the 210Pb skeletal burden. For this purpose, the effective half-life has been obtained from sequential measurements of 210Pb made in vivo during a 10-y period and by bioassay of 210Pb excreted in the urine of an individual with a 43-y-old body burden. The long-term effective half-lives obtained by these two methods were 18.1 +/- 4.8 y and 15.8 +/- 0.8 y, respectively. These values are not very different from the estimate of 12.3 y previously adopted by the ICRP. PMID- 1628988 TI - Fractional absorption of ingested barium in adult humans. AB - A reanalysis of available data on gastrointestinal absorption of soluble barium indicates that absorption has been underestimated in most human studies. There appears to be little basis for assigning a substantially lower absorption fraction to soluble barium than to other alkaline earth elements, particularly radium, in radiation protection guidance. PMID- 1628989 TI - Determining the normal concentration of uranium in urine and application of the data to its biokinetics. AB - A method was developed to determine the concentration of uranium (238U) in urine. This method involved preconcentration of uranium from urine with calcium phosphate neutron activation followed by simple radiochemical separation. Using this method, it was possible to detect 0.2 ng of 238U. The average and geometric mean concentration of uranium found in urine of subjects from a normal background environment was 12.8 and 9.4 ng L-1, respectively. The concentration of uranium in the urine and the daily intake of uranium by the same population was used to arrive at the gastrointestinal absorption factor (f1) for uranium incorporated in the diet. The f1 factor was estimated to be 1.6%. PMID- 1628990 TI - A methodology for estimating the radiological consequence of an acute aqueous release. AB - Assumptions supporting a chronic aqueous release methodology are inappropriate for estimating dose from accidental discharges. A method of modeling acute or accidental releases is being developed for predicting maximum individual dose. Standardization of consumption rates and usage factors for acute aqueous releases is necessary. Water-to-sediment transfer models describing waterborne deposition should be reviewed for applicability during short time regimes. PMID- 1628991 TI - In-situ gamma-ray site characterization of the Tatum Salt Dome Test Site in Lamar County, Mississippi. AB - Field surveys of gamma-ray emitting nuclides and soil core sampling were conducted at 12 sites on the Tatum Salt Dome Test Site and surrounding control areas to determine exposure rates from surficial radioactivity. 137Cs was the only man-made radionuclide detected and was most abundant at three off-site locations on cultivated lawns. 137Cs inventories at all of the on-site survey locations were lower than expected, given the high annual precipitation in the area. The vertical distributions were more extended than those reported for undisturbed sites. Pressurized ion chamber measurements indicated no significant differences in exposure rates on and off the test site. PMID- 1628992 TI - Optimum 222Rn-adsorbing activated charcoals. AB - Adsorptive and desorptive data are presented for 20 activated charcoal (AC) types that may be used in passive 222Rn sampling devices. Open-faced AC canisters were exposed for 3 d at room temperature to known radon and water vapor concentrations. Gamma measurements of radon progeny activity show that the optimum radon-adsorbing ACs are Calgon-PCB, Norit (RI, RBI, or PK), and, to a lesser degree, Witco-965 and ENV-EI-1220. PMID- 1628993 TI - In-line Kevlar filters for microfiltration of transuranic-containing liquid streams. AB - The Department of Energy Rocky Flats Plant has numerous ongoing efforts to minimize the generation of residue and waste and to improve safety and health. Spent polypropylene liquid filters held for plutonium recovery, known as "residue," or as transuranic mixed waste contribute to storage capacity problems and create radiation safety and health considerations. An in-line process-liquid filter made of Kevlar polymer fiber has been evaluated for its potential to: (1) minimize filter residue, (2) recover economically viable quantities of plutonium, (3) minimize liquid storage tank and process-stream radioactivity, and (4) reduce potential personnel radiation exposure associated with these sources. Kevlar filters were rated to less than or equal to 1 mu nominal filtration and are capable of reducing undissolved plutonium particles to more than 10 times below the economic discard limit, however produced high back-pressures and are not yet acid resistant. Kevlar filters performed independent of loaded particles serving as a sieve. Polypropylene filters removed molybdenum particles at efficiencies equal to Kevlar filters only after loading molybdenum during recirculation events. Kevlars' high-efficiency microfiltration of process-liquid streams for the removal of actinides has the potential to reduce personnel radiation exposure by a factor of 6 or greater, while simultaneously achieving a reduction in the generation of filter residue and waste by a factor of 7. Insoluble plutonium may be recoverable from Kevlar filters by incineration. PMID- 1628994 TI - Sealants for 222Rn exclusion. PMID- 1628996 TI - The twentieth anniversary of Heart & Lung: the Journal of Critical Care. PMID- 1628995 TI - Comments on maximum permissible concentrations. PMID- 1628997 TI - Take pride in our past: be challenged by the future. PMID- 1628998 TI - Infection control issues for critical care units: an overview and challenge- physician and nurse perspective. PMID- 1628999 TI - Pharmacotherapy update. PMID- 1629000 TI - Perceived threats of individuals recovering from myocardial infarction. AB - Lazarus' phenomenological theory of stress and coping provided the basis for this descriptive study of perceived threats after myocardial infarction (MI). Sixty four post-MI subjects enrolled in phase II cardiac rehabilitation programs identified threats they had experienced in the past month. Perceived threats were defined as situations that were difficult or troubling to the individual and were described by respondents in narrative form. Degree of threat was then measured by one item on which subjects indicated the degree of concern the threatening event had caused them. Responses to the one item were analyzed and categorized into the following five areas: physical problems; medical therapy/self-care; work/physical activity; interpersonal/family; and financial. The results provide an overview of the multiple concerns individuals deal with after a major life-threatening cardiac event. PMID- 1629001 TI - Coping with acute myocardial infarction. AB - This study examines how patients with acute myocardial infarction (AMI) cope. The nonrandom sample consisted of 30 acutely ill patients with AMI. Data were collected with an open-ended interview derived from cognitive coping theory and the Jalowiec Coping Scale. Interview content was analyzed with qualitative methods; data collected by use of the JCS were quantitatively examined. From the patients' appraisals emerged a unique description of coping with AMI that differed from the denial-focused description proposed by earlier investigators. In addition, patients used many and varied coping strategies during the first 3 days of illness. Among those contributing most to the total coping efforts of the group were the optimistic-, confrontive-, self-reliant-, and supportant-type strategies. Contrary to findings of earlier investigators, there was little evidence of attempts by patients with AMI to deny the existence of the illness as a means of coping. PMID- 1629002 TI - An examination of stressors in the patient undergoing cardiac electrophysiologic studies. AB - This study was undertaken to (1) identify stressors that medically treated patients who undergo cardiac electrophysiologic studies (EPS) experience from the points of view of patients and the staff nurses who care for them, (2) compare patients' and nurses' perceptions of such stressors, and (3) evaluate a tool developed by the investigator, the EPS Stressor Scale. Stressors were measured by scores on a scale from one to five. Demographic and health-related information was also obtained from patient subjects. The sample comprised 28 patients receiving EPS and 13 nurses. In general, illness-related stressors were most stressful to both patient and nurse subjects, whereas hospital-related stressors were least stressful. Patient and nurse subjects rank ordered stressors similarly; however, t tests revealed significant differences between patients' and nurses' mean stress scores on stressors. The EPS Stressor Scale appears to be a useful tool in evaluating the stress experienced by patients undergoing EPS; however, this tool will need to be validated in different groups of these patients. Implications for nursing practice are also discussed. PMID- 1629003 TI - Sleep patterns and stress in patients having coronary bypass. AB - This study examined the self-reported sleep patterns of adult patients undergoing coronary artery bypass graft (CABG) surgery and the relationship between their perceived illness-related stress and sleep disturbances. Twenty-four patients completed data at all three collection points: preadmission, and the third and sixth postoperative mornings. Patients responded to the Verran/Snyder-Halpern Sleep Scale and the Carr and Powers Stressor Scale for patients having CABG. By use of a within-subject, one-factor, repeated measures analysis of variance, statistically significant differences were found in each of the three sleep dimensions measured over time (disturbance, effectiveness, and supplementation). With the Pearson correlation, the hypothesis that sleep disturbances in patients having open-heart surgery are related to psychologic stress associated with illness was not supported. Additional analyses indicated that hospital and illness-related stress, duration of cardiopulmonary bypass, anesthesia time, and sleep medication were related to patients' sleep disturbance, effectiveness, or supplementation in different ways and at different times during the study periods. PMID- 1629004 TI - Treatment of paroxysmal supraventricular tachycardia with adenosine: implications for nursing. AB - Paroxysmal supraventricular tachycardia (PSVT) is a frequently occurring arrhythmia. Currently, verapamil and manual vagal stimulation are the first-line interventions for PSVT. Although verapamil is widely used for the treatment of PSVT, it can result in hypotension and ventricular fibrillation if given to a patient with ventricular tachycardia. Because the differential diagnosis of broad QRS complex tachycardia is difficult, the development of a safer drug for the treatment of both narrow- and broad-complex tachycardia is extremely important. Adenosine is a promising new drug for the treatment of PSVT. Its use is reviewed in three presentations. PMID- 1629005 TI - Transcatheter closure of ventricular septal defect: a nonsurgical approach to the care of the patient with acute ventricular septal rupture. AB - Acute ventricular septal rupture is a potentially fatal complication of myocardial infarction. In the past, surgical repair was the only treatment option for this life-threatening event. However, not all patients are good surgical candidates. Transcatheter closure of a ventricular septal defect (VSD) with a prosthesis called the Rashkind Patent Ductus Arteriosis Occluder System allows closure of the VSD without the possible complications associated with open-heart surgery. This treatment has potential as a temporary measure for patients awaiting surgical repair of VSD. Transcatheter closure may also be used as a permanent treatment for those patients considered to be poor surgical candidates. This case presentation addresses the use of a state-of-the-art nonsurgical approach to VSD closure. The focus is on the unique medical and nursing interventions used in caring for the patient suffering from a myocardial infarction complicated with postinfarction ventricular septal defect. PMID- 1629006 TI - Coronary precautions: should caffeine be restricted in patients after myocardial infarction? AB - The effect of caffeine on heart rate, blood pressure, and cardiac rhythm has long been a controversial issue. A review of the literature reveals numerous articles evaluating the effects of caffeine on normal subjects, fewer evaluating the effects of caffeine on patients with cardiac disease and patients after myocardial infarction. Although the findings for the various populations have been inconsistent, recent studies with large cohorts have clarified the issue. Moderate consumption of caffeine does not significantly increase the risk of a coronary event nor increase the frequency of cardiac arrhythmias. This conclusion applies to healthy persons, patients with ischemic heart disease, and those with serious ventricular ectopy. Patients with cardiac disease should be allowed to consume four to five cups of caffeinated beverages per day while in the coronary care unit or progressive care unit under the surveillance of nursing staff. PMID- 1629007 TI - Recommendations for improving cardiopulmonary resuscitation skills retention. AB - Massive community efforts are devoted to delivering cardiopulmonary resuscitation (CPR) training to health professionals and lay people. However, although most people can successfully learn to perform CPR, skills retention is universally poor. Beginning as early as 2 weeks after initial training, CPR skills begin to deteriorate in a wide variety of subjects including nurses, physicians, emergency medical technicians, family members of patients with cardiac disease, and other lay people. Methods tested to improve retention are reviewed, and the role of practice and review is examined. The failure of many factors to improve retention of CPR skills is discussed. Finally, suggestions for improvement in retention of CPR skills based on a review of the literature and pertinent theory are offered. PMID- 1629008 TI - Challenges in nursing: infants with congenital diaphragmatic hernia. AB - Despite advances in the care of infants born with congenital diaphragmatic hernia, mortality rate continues to be high. Immediate survival is directly related to the degree of pulmonary hypoplasia present. The spectrum is wide, from minimal pulmonary hypoplasia, in which neonates do well, to severe pulmonary hypoplasia, which is incompatible with life. Between these two extremes lie infants with compromised pulmonary function whose long-term survival depends on the clinical strengths of their multidisciplinary team. Over the past year, 23 infants with congenital diaphragmatic hernia were cared for in the Multidisciplinary Intensive Care Unit at Children's Hospital, Boston. A retrospective chart review enabled the authors to describe the trajectory of illness and generate nursing practice guidelines. This article presents the nursing care issues that were identified in this challenging population. PMID- 1629010 TI - Guidelines for critique of a research report. AB - Before findings reported in a research article are used to change clinical practice, the research must be evaluated for evidence of credibility, integrity, and potential for replication. This paper provides guidelines for use in evaluating deductive, empirical research. The standards presented in this paper are derived from the tenets of the scientific method, measurement theory, statistical principles, and research ethics. The guidelines may be used to evaluate each section of a research report, from the title to the interpretation of findings. PMID- 1629009 TI - Maximal rate response in a permanent pacemaker during chest physiotherapy. AB - Rate-responsive pacing is designed to allow a near-physiologic heart rate response to patient activity. One means of generating the desired response has been achieved with the use of pacemakers that respond to vibration generated by skeletal muscle activity. In this article, we report a case of increased paced rate in an activity-sensing rate-responsive pacemaker caused by the sensing of skeletal muscle vibration during chest physiotherapy. Potential clinical complications and possible solutions to this problem, as well as significant aspects of nursing care, are discussed with respect to patients with rate responsive pacing devices. PMID- 1629011 TI - Spotlight article: the effect of familiar and unfamiliar voice treatments on intracranial pressure in head-injured patients. (Treolar DM, Nalli BJ, Guin P, Gary R. J Neuroscience Nurs 1991;23(5):295-9.). PMID- 1629012 TI - Herpes simplex meningoencephalitis. PMID- 1629013 TI - Labelling of leukocytes with 99mTc-HMPAO for scintigraphy of inflammatory lesions and abscesses. AB - A simplified and efficient procedure for 99mTc-HMPAO-labelling of leukocytes is described. For this purpose, the pH and concentration of the 99mTc-HMPAO preparation was modified. Leukocytes were isolated from a 20 mL mixture of patient blood, 5 mL ACD and 0.8 mL methylcellulose after 1 h sedimentation of erythrocytes and centrifugation (at 400 g) of the obtained plasma layer. Simultaneously, 99mTc-HMPAO was prepared (one single-dose kit for two patients) by adding 2.2 mL 99mTc-generator eluate and, after 10 min, 0.3 mL of phosphate buffer to lower the pH to 7. The isolated WBCs were then labelled by the addition of 1-1.2 mL of 99mTc-HMPAO solution and incubated for 20 min. The unbound tracer was then discarded, the labelled WBC washed and finally resuspended in autologous cell-free plasma. Leukocytes labelled by this procedure were used for scintigraphic localization of inflammatory lesions and abscesses in the gastro intestinal tract. The labelling efficiency was 60 +/- 9%, with a separation yield of 55 +/- 11%. PMID- 1629014 TI - Estrogen receptor imaging with 17 alpha-[123I]iodovinyl-11 beta-methoxyestradiol (MIVE2)--Part I. Radiotracer preparation and characterization. AB - It is important to know the estrogen receptor rate in breast carcinoma management. Thus, an in vivo and atraumatic method would be very useful. Different ligands have been proposed for this. We present here the specific synthesis of 20E- and 20Z-17 alpha-iodovinyl-11 beta-methoxyestradiols and their biological characterization as estrogen receptor ligands. The two isomers were analysed by current chemical methods (NMR) and purified by HPLC. We carried out an in vivo study with 21-day-old Swiss mice to compare properties of the two ligands. The 20E-MIVE2 showed the best affinity for estrogen receptors, the uterus-to-blood ratio was 15-fold higher for the trans derivative. We enhanced the in vivo and in vitro properties of the 20E-MIVE2: the affinity constant was determined by Scatchard analysis, Kd = 16 x 10(-10) M, and biodistributions were performed with unlabelled estradiol pre-injection. We concluded that 20E-MIVE2 can be used for a feasibility study in patients with breast carcinoma. PMID- 1629015 TI - Estrogen receptor imaging with 17 alpha-[123I]iodovinyl-11 beta-methoxyestradiol (MIVE2)--Part II. Preliminary results in patients with breast carcinoma. AB - 17 alpha-[123I]Iodovinyl-11 beta-methoxyestradiol was injected into 19 women: group 1 (n = 8), initial evaluation of breast cancer; group 2, (n = 11) postoperative follow-up including 9 patients with bone metastases. The primary tumor (size: 8-10 mm) was visualized by breast tomoscintigraphy in 2/4 patients of group 1 with high estrogen receptor concentration (162-445 fmol/mg) and was not detectable in 4 patients with low estrogen receptor concentration (6-32 fmol/mg). Axillary lymph node metastases were detected in 1 patient of group 1 and in 1 patient of group 2. In 4 patients of group 2 with previous primary tumor containing estrogen receptors, MIVE2 uptake in bone metastases was demonstrated. MIVE2 scintigraphy is an original, specific and non-invasive method for breast cancer estrogen receptor imaging in primary and in metastatic tumors. PMID- 1629016 TI - Labeling proteins with fluorine-18 using N-succinimidyl 4-[18F]fluorobenzoate. AB - Two methods were investigated for the no-carrier-added synthesis of N succinimidyl 4-[18F]fluorobenzoate (S[18F]FB). The first, an attempted nucleophilic aromatic substitution by [18F]fluoride on N-succinimidyl 4 nitrobenzoate was unsuccessful. The second method involved three steps; [18F]fluoride for trimethylammonium substitution on 4-formyl-N,N,N trimethylanilinium triflate, oxidation to 4-[18F]fluorobenzoic acid, followed by reaction with N-hydroxysuccinimide and dicyclohexylcarbodiimide to form S[18F]FB. Total synthesis and purification time was 100 min and the overall radiochemical yield was 25% (decay corrected). A monoclonal antibody F(ab')2 fragment could be labeled in 40-60% yield by reaction with S[18F]FB for 15-20 min. The tissue distribution in normal mice and in vitro tumor binding of the antibody F(ab')2 labeled by reaction with S[18F]FB were comparable to those observed for the fragment after radioiodination using N-succinimidyl 4-[125I]iodobenzoate. PMID- 1629017 TI - Incorporation of radioiodinated IPPA and BMIPP fatty acid analogues into complex lipids from isolated rat hearts. AB - Heart lipids were extracted by the Folch technique from Langendorff-perfused rat hearts after administration of 15-(p-[131I]iodophenyl)pentadecanoic acid and 15 (p-[125I]iodophenyl)-3-R,S-methylpentadecanoic acid. Techniques utilizing successive high performance liquid chromatographic (HPLC) analyses have been developed for the evaluation of the uptake of the tracers into neutral lipids and phospholipids of the rat hearts. Phospholipids were separated on a SiO2 column eluted with a gradient of acetonitrile/water (97.5/2.5) and acetonitrile/water (85/15) followed by separation of the neutral lipids on a C-18 reversed phase column with a gradient consisting of acetonitrile and 2-propanol/hexane (60/40) containing 1 N H2SO4 (5 microL/100 mL). Both tracers show the incorporation into the expected major lipid classes. PMID- 1629018 TI - N-(m-[125I]iodophenyl)maleimide: an agent for high yield radiolabeling of antibodies. AB - In an effort to radiolabel antibodies, N-(m-[125I]iodophenyl)maleimide (m [125I]IPM) was prepared by the demetallation of an N-[m-tri-(n butyl)stannylphenyl]maleimide intermediate. The unlabeled intermediate was synthesized in greater than or equal to 75% yield using a palladium catalyzed reaction of hexabutylditin with m-bromoaniline, followed by reaction with maleic anhydride and ring annulation. All products were confirmed by NMR and elemental analysis. Labeling with 125I was carried out in a biphasic mixture containing chloramine-T (radiochemical yield greater than or equal to 70%). Rabbit IgG modified with the heterobifunctional crosslinking agent N-succinimidyl-3-(2 pyridyldithio)propionate (SPDP) and bovine serum albumin were conjugated with m [125I]IPM (yield: 40 and 80%, respectively). In addition, m-[125I]IPM was conjugated to rabbit IgG subunits (HL) in 70% yield. The in vitro stability of the radiolabeled proteins in serum showed less than 1% deiodination over 24 h. PMID- 1629019 TI - m-[125I]iodoaniline: a useful reagent for radiolabeling biotin. AB - Biotinyl-m-[125I]iodoanilide (BIA) was synthesized by coupling biotin to m [125I]iodoaniline via a mixed anhydride reaction. m-[125I]Iodoaniline was produced from the tin precursor, which was prepared using a palladium catalyzed reaction of hexabutylditin with m-bromoaniline. The radioiodinated BIA derivative is characterized by a stable amide and/or intact ureido group on the biotin molecule; it may thus be a useful carrier for targeting radionuclides to avidin conjugated antibodies previously localized on tumors. PMID- 1629020 TI - Technetium-99m p-iodophenethyldiaminodithiol (DADT-IPE): potential brain perfusion imaging agent for SPECT. AB - A new ligand, an N-p-iodophenethyl diaminodithiol (DADT-IPE), an anlog of N isopropyl-p-iodoamphetamine (IMP), was synthesized and subsequently complexed with 99mTc, using stannous chloride as a reducing agent. Two complexes (a and b) were separated from 99mTc-DADT-IPE by high performance liquid chromatography (HPLC). Competitive inhibition studies showed that the IC50 value of DADT-IPE (70 microM) was similar to that of IMP (49 microM). Biodistribution studies of one of the complexes [99mTc-DADT-IPE(a)] in rats showed that 0.65% of the injected dose of the tracer remained in the brain at 5 min after intravenous injection, with 0.53% of the dose remaining in the brain at 60 min post-injection, whereas the corresponding values for the other complex [99mTc-DADT-IPE(b)] were 0.34% dose in the brain at 5 min and 0.28% dose in the brain at 60 min post-injection. The half life for clearance of 99mTc-DADT-IPE(a) from rat brain was found to be more than 5 h. These results suggested that 99mTc-DADT-IPE(a) has characteristics which are suitable for cerebral perfusion imaging. PMID- 1629021 TI - 4-Borono-2-[18F]fluoro-D,L-phenylalanine: a possible tracer for melanoma diagnosis with PET. AB - The potential of 4-borono-2-[18F]fluoro-D,L-phenylalanine ([18F]FBPA), a flurodinated derivative of a target compound for boron neutron capture therapy, for melanoma imaging by positron emission tomography (PET) was studied using animal models. A high uptake of [18F]FBPA was found in murine B16 melanoma or in Greene's melanoma No. 179, a melanotic cell line in hamsters, for the first 6 h after injection. Whole body autoradiography using [18F]FBPA gave a clear image of the B16 tumor. The acid-insoluble 18F in the B16 increased to 27% by 6 h, and most of the free 18F was detected as [18F]FBPA in both B16 and plasma. In the hamster models, No. 179 showed a 1.7 times higher uptake than amelanotic Greene's melanoma No. 178 at 6 h post-injection, although both melanomas indicated similar metabolic activities when examined by a tracer uptake study using L [14C]methionine, 2-deoxy-D-[14C]glucose and [3H]thymidine. [18F]FBPA may be a very promising PET tracer for melanoma imaging. PMID- 1629022 TI - Potential 67Ga radiopharmaceuticals for myocardial imaging: tris(1-aryl-3-hydroxy 2-methyl-4-pyridinonato)gallium(III) complexes. AB - A series of highly lipophilic complexes of 1-aryl-3-hydroxy-2-methyl-4 pyridinones with gallium(III)-67 has been evaluated in vitro and in vivo as potential radiopharmaceuticals. The pyridinones have different substituents at the para-position of the phenyl ring: R = H, CH3, OCH3 and NO2. Biodistribution studies of 67Ga complexes have been carried out in rabbits, mice, rats and a dog. High heart uptake of the radionuclide has been shown in rabbits and the dog. The different biodistribution patterns in mice and rats indicate that there is a species difference in the biodistribution of these complexes. Rabbits and the dog show rapid heart uptake and blood clearance. The speciation of the Ga3+ ion in vivo is simulated in vitro with a simple blood plasma model based on the available thermodynamic data. PMID- 1629023 TI - Radioiodinated 2-hydroxy-3-(4-iodophenyl)-1-(4-phenylpiperidinyl)propane: potential radiotracer for mapping central cholinergic innervation in vitro. AB - Radioiodinated 2-hydroxy-3-(4-iodophenyl)-1-(4-phenylpiperidinyl)propane, 5 (4 HIPP), was synthesized and evaluated as a simple vesamicol-like radiotracer for mapping cholinergic pathways in the brain. Both enantiomers of 5 exhibit significant accumulation (approx. 2% of injected dose) and prolonged retention (t1/2 greater than 3 h) within the rat brain. The accumulation of radioiodinated 5 in the rat brain was reduced by up to 70% in the presence of vesamicol and its analogs. The levorotary isomer (-)-4-[123I]HIPP exhibits significant accumulation in the monkey brain, with a half-life of about 9 h. Radioiodinated 5 may therefore be a useful tool for studying cholinergic pathways in the brain. PMID- 1629024 TI - Assessment of iodohexadecenoic acid as a tracer of fatty acid metabolism by external detection: a study on isolated rat heart. AB - Labelled fatty acids have been proposed to explore cardiac metabolism. For the analysis of the external detection curve obtained with 16-iodo 9-hexadecenoic acid (IHA), we developed a mathematical 4-compartment model with compartments 0, 1, 2 and 3 representing vascular IHA, intracellular IHA, esterified forms and iodide, respectively. This model, used here for isolated rat hearts perfused in a recirculating system, is validated by an intracellular analysis, then tested in various metabolic conditions. Thus, the mathematical analysis of the external detection curve gives us numerical data on IHA metabolism, especially the distribution between degradation and storage. Our results confirm the suitability of IHA for assessing myocardial metabolism. PMID- 1629025 TI - Evaluation of osmium(II)-nitrosyl complexes as a method to increase the yield of the 191Os-191mIr generator. AB - The nitrosyl complexes pentachloronitrosylosmate(II), [OsCl5(NO)]2-, and hydroxytetranitronitrosylosmate(II), [Os(OH)(NO2)4(NO)]2-, were evaluated as parent species for use on the 191Os-191mIr generator in an attempt to increase the 191mIr yield of the generator by providing a direct route to a chemically stable 191mIr daughter. The uptake of the 191Os-labeled complexes by the inorganic ion-exchangers ZrO2, SnO2, PbS, MnO2 and Al2O3 and the organic resin AG MP-1 was measured and prototype generators were prepared using those exchangers that demonstrated greater than 90% uptake of the 191Os-labeled complexes. The 191mIr(III)-nitrosyl complexes produced subsequent to beta- decay of the 191Os nitrosyl parent complexes were found to undergo secondary chemical reactions to form nitro (NO2-) complexes that were tightly retained on the ion exchanger limiting 191mIr yield to less than 5%. PMID- 1629026 TI - Preparation and evaluation of 17-ethynyl-substituted 16 alpha [18F]fluoroestradiols: selective receptor-based PET imaging agents. AB - We have prepared and studied six new analogs of 16 alpha-fluoroestradiol (FES): 17 alpha- and 17 beta-ethynyl-FES (7 [FEES] and 7a), and the 11 beta-ethyl (8 and 8a) and 11 beta-methoxy (9 and 9a) derivatives, novel estrogen receptor-based PET imaging agents. The relative binding affinity (RBA) for the estrogen receptor (ER) versus FES is increased for 7, 9 and 9a but decreased for 7a, 8 and 8a. All six analogs have been labeled in the 16 alpha position with 18F by the nucleophilic displacement of the corresponding 16 beta-trifluoromethanesulfonate with nBu4N18F. Subsequent ethynylation with lithium trimethylsilylacetylide yielded the FEES analogs (total synthesis time: 120 min; effective specific activity: 200-2400 Ci/mmol). Selective uptake in the uterus was high for [18F]7, [18F]8, [18F]9 and [18F]9a (% ID/g values at 1 h: 11.2, 12.9, 9.9 and 8.3, respectively), while uptake was effectively blocked by coinjection of an excess of unlabeled estradiol. The FEES analogs, [18F]7, [18F]8 and [18F]9, exhibited the highest selectivity, in terms of target (uterus)-to-blood ratios, ever seen amongst estrogen radiopharmaceuticals, 154, 145 and 169, respectively. The analogs [18F]7a and [18F]8a displayed no uptake in the uterus, consistent with their low RBAs. Metabolism studies revealed that most of the uterine activity is unmetabolized while the blood exhibits a rapid and subsequently sustained mixture of metabolites. The muscle shows a metabolic profile intermediate to the uterus and blood. These analogs provide an array of desirable characteristics for the optimal PET imaging of ER-rich target tissues. PMID- 1629027 TI - Non-beta-oxidizable omega-[18F]fluoro long chain fatty acid analogs show cytochrome P-450-mediated defluorination: implications for the design of PET tracers of myocardial fatty acid utilization. AB - The nature of the in vivo defluorination of non-beta-oxidazable no-carrier-added omega-[18F]fluoro long chain fatty acid (LCFA) analogs was studied with the aim of developing PET tracers of LCFA utilization. Extensive defluorination of 15 [18F]fluoro-3-thia-pentadecanoic acid (FTPA) in mouse was evidenced by radioactivity uptake by bone. [18F]Fluoride in the blood was verified analytically. Incubations of FTPA in rat-liver homogenates and subcellular fractions thereof showed a strong defluorination process in microsomes which was O2- and NADPH-dependent. In contrast, defluorination of FTPA was relatively slow in Langendorff perfused rat heart. High bone uptake in mouse was also observed with 14-[18F]fluoro-13,13-dimethyl-3-thia-tetradecanoic acid, where gem-dimethyl substitution precludes direct elimination of H18F. These data indicate that the defluorination of non-beta-oxidizable omega-[18F]fluoro LCFA analogs is primarily governed by cytochrome P-450-mediated omega-oxidation. Therefore, labeling at the (omega-3) carbon was proposed to provide a more stabile 18F-label. Defluorination of the (omega-3)-labeled 13 (R,S)-[18F]fluoro-3-thia-hexadecanoic acid was lower than that of FTPA in mouse and was independent of O2 and NADPH in vitro. Thus, (omega-3) labeling with 18F is preferable to omega labeling of non-beta oxidizable LCFA analogs. PMID- 1629028 TI - Lung scintigraphy with [123I]IMP in patients with pulmonary tuberculosis. AB - Lung scintigraphy using N-isopropyl-p-[123I]iodoamphetamine (IMP) was performed on 26 patients with pulmonary tuberculosis. Early (5 min after injection) and late images (4 h after injection) were obtained with a large-field gamma-camera equipped with a digital computer. Lung scintigraphy using [99mTc]MAA (MAA) was also done. Although early IMP images showed the same findings as [99mTc]MAA, images, a discrepancy between delayed IMP images and [99mTc]MAA images was seen in some patients. Increment of activities seen in late images was demonstrated in most patients whose chest x-ray findings included exudative inflammatory changes. Uptake and clearance of IMP was considered to be affected by the active phase of pulmonary tuberculosis. PMID- 1629029 TI - In vivo studies of unlabeled and radioiodinated rhodamine-123. AB - Radioiodinated rhodamine-123 (Rh123), potential tumor imaging agent, was injected in mice bearing experimentally-induced tumors to investigate its tissue distribution. Some accumulation of radioactivity was found in tumors; most of it cleared rapidly from the blood after injection. Also, the radioiodinated Rh123 had metabolized to water-soluble species which was excreted in urine and feces. Unlabeled Rh123, on the other hand, accumulated only marginally in the tumors. However, it was found to accumulate significantly in the heart; as much as seventy times the level in blood at 4 h post-injection. Accumulation of unlabeled Rh123 increased steadily even at 24 h post-injection; whereas, it cleared rapidly from the blood via the kidney. This finding of selective accumulation of Rh123 in heart could be exploited in synthesizing 11C- and 18F-labeled Rh123 for use in PET studies of the myocardium. PMID- 1629030 TI - Quantitative assessment of lipoprotein metabolism by positron emission tomography with an 18F-containing residualizing label. AB - Residualizing labels for proteins are designed to remain entrapped within cells following uptake and degradation of the carrier protein. In the present work we report the synthesis of a novel residualizing label, N-lactitol-S ([18F]fluorophenacyl)-cysteamine ([18F]LCSH, and its use for quantifying the accumulation of low density lipoprotein in tissues in vivo by positron emission tomography (PET). The retention of degradation products in tissues from lipoprotein or from other rapidly catabolized protein pharmaceuticals tagged with [18F]LCSH reduces leakage of tracer into the plasma compartment. Thus, residualizing labels provide a valuable tool for enhancing signal-to-noise ratios, even during the relatively short interval of PET studies. PMID- 1629031 TI - Streptavidin-biotinylated IgG conjugates: a simple procedure for reducing polymer formation. AB - Disulfide links of the IgG2ak anti-ovarian carcinoma antibody, 5G6.4, were site specifically biotinylated [approximately 2 biotins/IgG2a] using a novel crosslinking procedure using the biotin derivatized ETAC (equilibrium transfer alkylation crosslink reagent) 1a. Complexation of ETAC 1a biotinylated 5G6.4 on a column of immobilized protein A at high dilution, followed by passage of [125I]streptavidin, washing and pH change leads to elution of a streptavidin-free product with a molecular mass in the 200-300 kDa range. By contrast, direct mixing with [125I]streptavidin rapidly gave larger oligomers of much greater than 669 and approximately 440-669 kDa molecular mass, respectively. The biodistribution of the 200-300 kDa complex showed significantly diminished liver, kidney and spleen uptake as well as higher blood activity than the 440-669 kDa complex. The methodology represent the first application of ETAC chemistry to disulfide-bond directed biotinylation of antibodies and the synthesis of streptavidin antibody conjugates which minimizes their polymerization. PMID- 1629032 TI - Repeated DNA sequences of Aegilops markgrafii (Greuter) Hammer var. markgrafii: cloning, sequencing and analysis of distribution in Poaceae species. AB - Total DNA of Aegilops markgrafii (Greuter) Hammer var. markgrafii was shot gun cloned. From all the recombinants containing repetitive sequences 1-2% hybridized preferentially with the Ae. markgrafii genome and were almost absent in wheat. The cloned sequences are disperse distributed over the Aegilops chromosomes and show the typical features of eukaryotic repetitive DNA. Five specific probes were tested for their applicability in a screening program on 68 Poaceae accessions. PMID- 1629033 TI - National psychology, national socialism, and analytical psychology: reflections on Jung and anti-semitism. Part II. AB - The paper is a critical study of the intellectual relations of analytical psychology and national socialism. I try to show that it was Jung's attempt to establish a psychology of nations that brought him into the same frame as Nazi anti-semitic ideology. In addition, Jung was absorbed by the question of leadership, also a pressing issue during the 1930s. Exploring these ideas as thoroughly as possible leads to a kind of reparation, for I think that post Jungians do have reparation to make. Then it is possible to revalue Jung's overall project in more positive terms. By coupling a less simplistic methodology and a more sensitive set of values to Jung's basic intuitions about the importance of a psychology of cultural difference, analytical psychology has something to offer a depth psychology that is concerned with processes of political and social transformation. PMID- 1629034 TI - 'There is no such thing as a liberal dictatorship': discovery and first publication of a letter on politics by C. G. Jung. PMID- 1629035 TI - Oedipus in Gethsemane: archetypal aspects of homosexuality. AB - In the history of depth psychology, we often come upon the theme of 'father-son' relationships, which, although initially positive, ultimately become destructive. I submit that repressed homosexual aspects may be responsible for this turn of events and illustrate this hypothesis with archetypal motifs found in Greek and Judaeo-Christian culture. PMID- 1629036 TI - Looks that kill the capacity for thought. AB - In this paper I explore ways in which the fundamental balance between life and death forces is portrayed within the Oedipus myth, showing how there are times when, as theorists, we are blind to the on-going dynamic polarities contained within the myth. Using clinical case material I explore the vicissitudes of the theme of infanticide and the impact of the infanticidal impulse on thinking processes and how things come together in the mind. I consider the link between the infanticidal impulse and what may be being symbolized by physiological problems with eyes and wombs. I give examples of the clinical use I have made of a variety of theoretical ideas which enabled my capacity for thought at those times when much of what was taking place was unthinkable. PMID- 1629037 TI - The therapeutic function of altered states. PMID- 1629038 TI - Incidence of otitis media in CBA/J and CBA/CaJ mice. AB - The inbred CBA/J mouse has become a standard experimental animal for auditory study because of its lifelong good hearing. In a newly established mouse breeding colony that housed CBA/J and CBA/CaJ mice to reared as auditory subjects, otitis media frequently afflicted CBA/J mice, reaching an incidence of 90% in animals greater than 400 days of age. Otitis media was not found in CBA/CaJ mice. Three attempts to establish a colony that was free of otitis were unsuccessful. Although the primary pathogen was not clearly established, Pasteurella pneumotropica was isolated from infected bullae. Partial control of otitis media followed the introduction of tetracycline prophylaxis. The CBA/CaJ mice may be suitable replacements for CBA/J mice in studies that require inbred mice with good hearing, since their auditory thresholds did not differ significantly from those of otitis-free CBA/J mice. PMID- 1629039 TI - Analytic listening by the goldfish. AB - A stimulus generalization paradigm was used with classical respiratory conditioning to study analytic listening in the goldfish. Animals were first conditioned to suppress respiration upon the presentation of a long-duration complex sound comprised of two sinusoidal components, 166 and 724 Hz. Conditioned animals were then presented with a set of eight novel test tones with frequencies between 95 and 1514 Hz, and including 166 and 724 Hz. Response magnitudes were greatest at the frequencies of the components making up the complex to which the animals were initially conditioned. This is a demonstration that the goldfish had acquired independent information about the frequencies of the individual sinusoidal components making up a complex sound, and thus had listened to the complex analytically. To my knowledge, this is the first demonstration of simultaneous frequency analysis and analytic listening by a nonhuman animal, and suggests that this fundamental aspect of human hearing may be a primitive character shared with the fishes and perhaps with all living vertebrates. PMID- 1629040 TI - Maturation of kinocilia in amphibian hair cells: growth and shortening related to kinociliary bulb formation. AB - New hair cells are added to the amphibian sacculus throughout life, primarily at its outer edge. The stereociliary bundles near that edge are heterogeneous, but eventually develop the more homogeneous morphology of the overwhelming majority of mature cells near the center of the epithelium. During their development the kinocilium grows and a kinociliary bulb forms. It has been proposed that initial elongation of the kinocilium is followed by shortening, and that the bulb may form during shortening. To test those hypotheses, amphibian sacculi were examined by scanning electron microscopy and the length of the kinocilium, the width of the kinociliary bulb, and the length of the tallest stereocilia were measured for 159 hair cells. The length of the tallest stereocilia on each hair cell was used as an indicator of the relative maturity of that cell, so that changes in the structure of each cell's kinocilium could be related to that cell's stage of development. Results indicate that initial elongation of the kinocilium is followed by shortening. Kinociliary bulbs first appear and increase in volume as shortening proceeds. These findings support the hypotheses. Models are proposed to explain how the formation of the bulb could result from depolymerization of apical cytoskeletal elements, and how kinocilium growth and shortening may contribute to hair bundle reorientation in the developing ear. PMID- 1629041 TI - Enkephalin-like immunoreactivity in cochlear efferents in the bat, Rhinolophus ferrumequinum [corrected]. AB - The cochlear efferent of the bat is anatomically different from other mammals. The olivocochlear bundle of the greater horse shoe bat, Rhinolophus ferrumequinum, projects only to inner hair cells. To examine the neurochemical nature of the olivocochlear bundle, we examined methionine-enkephalin-like immunoreactivity in this species. We observed immunoreactivity in the inner spiral bundles and in nerve fibers in the osseous spiral lamina. Sometimes immunostained inner spiral bundles were found to project towards inner hair cells. These data, as well as data from previous studies, suggest that cochlear efferents of different species of mammals share some common neurochemical features [corrected]. PMID- 1629042 TI - Evoked otoacoustic emissions in a nonlinear model of the cochlea. AB - A nonlinear, transmission-line-analog model of the ear is presented for the purpose of simulating the experimental data of delayed evoked otoacoustic emissions (DEOAEs). The model produces echoes very similar to DEOAEs in the latency, saturation and spectral features when hypothetical, highly damped points arranged on the BM with an equal spacing are assumed. Special attention is payed to the reason for the long latency of DEOAEs. In the model, the delay occurs spuriously by cancellation of components scattered from the irregular points and is longer than the simple round trip time of the travelling wave from the stapes to the place of characteristic frequency. The echoes in the model are basically linear for the low intensity stimuli and only when the stimuli surpass a certain level they saturate owing to the nonlinearity of the BM damping. PMID- 1629043 TI - A precedence effect in the perception of inter-aural cross correlation. AB - Does the precedence effect, well known in the field of sound localization or lateralization, also apply to other percepts based on binaural processing? We have compared, with one and the same experimental paradigm, a manifestation of the traditional precedence effect in lateralization with a possible similar effect in the perception of diffuseness or compactness of a sound image. With dichotic headphone stimulation, lateralization was controlled by the inter-aural time delay (IATD), and diffuseness/compactness by the inter-aural cross correlation (IACC). The experimental paradigm rests on the principle of estimating the over-all sensation of a 20-ms noise burst, which was subdivided in two parts, with the relevant dichotic information (IATD or IACC) in the leading part being opposite to that in the trailing part. When each part is 10 ms, it is found that the overall sensation is slightly dominated by the information in the leading part, both for lateralization and for compactness/diffuseness. This dominance of the leading part can be compensated by a certain decrease of its duration and/or amplitude relative to that of the trailing part. It is found that this quantitative measure for the 'strength' of the precedence effect for the present stimulus is essentially the same for IATD and IACC, suggesting that the precedence effect does not apply exclusively to sound localization or lateralization, but to at least one other percept based on binaural processing as well, namely the processing of inter-aural cross correlation. PMID- 1629044 TI - Effects of various noise exposures on endocochlear potentials correlated with cochlear gross responses. AB - Changes in endocochlear potentials (EP), cochlear microphonics (CM), and compound action potentials (CAP) with noise exposure were investigated in guinea pigs. The animals were anesthetized and immobilized and exposed to white noise at intensities ranging from 105 to 125 dB. The negative EP (N-EP) was induced by anoxia and was investigated during and after noise exposure. It was found that the general EP (G-EP, the sum of both positive EP (P-EP) and N-EP) increased remarkably during exposure to 115 dB noise but decreased during exposure to 125 dB noise. A smaller absolute value of N-EP was encountered only during exposure to 125 dB noise. The results shed light on the relationship between EP and CM, CAP changes, and the potential mechanism of EP change and its significance in noise-induced hearing loss. PMID- 1629045 TI - Physiological correlates of off-frequency listening. AB - Recordings are made from inner hair cells (IHC) in the second turn of the guinea pig cochlea where characteristic frequencies (CF) are approximately 4000 Hz. Results from experiments using two stimulus inputs suggest that the characterization of two-tone suppression at this more-basal recording location is similar to the reported for IHCs in the third turn (Cheatham and Dallos, 1989, 1990a, 1990b). For example, introduction of a suppressor causes IHC frequency response functions to become narrower with the smallest magnitude reductions occurring between 1/2 to 1 octave below CF. In this frequency region, where suppression is minimal, it was also observed that suppressor magnitude was reduced by the probe. In other words, the mutual suppression of probe and suppressor may contribute to the sharpening of these functions. Since the peak of the frequency response function shifts to a lower frequency in the presence of the suppressor, these results may provide a physiological correlate of the psychophysical phenomenon known as 'off-frequency listening.' PMID- 1629046 TI - Hair cell regeneration in the adult budgerigar after kanamycin ototoxicity. AB - Adult budgerigars were given kanamycin at a dose of 200 mg/kg/day for 10 successive days. At 1, 7, 14 and 28 days after the drug treatment, the cochleae of the birds were processed for scanning electron microscopy (SEM). Complete degeneration of sensory hair cells was observed in the basal 55-75% of the basilar papilla immediately after the treatment. Regenerating hair cells, characterized by clusters of microvilli and small apical surfaces, were present in the basal end of the papilla as early as one day post-treatment. During the 28 day recovery period, the number of hair cells progressively increased beginning at the base and spreading toward the apex. Although the appearance of the basilar papilla had improved considerably by 28 days post-treatment, the sensory epithelium still contained a number of pathologies, most noticeably, incomplete restoration of hair cell number in the most apical part of the damaged region and the disorganization of hair cell packing. These remaining pathologies may be responsible for the permanent threshold shifts observed in budgerigars exposed to the same dose of kanamycin treatment (Hashino and Sokabe, 1989). PMID- 1629047 TI - Hypothetical roles of middle ear muscles in the guinea-pig. AB - The attenuation of incoming sounds induced by acoustic reflex triggering was evaluated from the cochlear microphonic response to test tones in 45 awake guinea pigs. Although control electromyographic measurements proved that the stapedius muscle was contracting, neither impedance changes nor attenuation induced by contralateral reflex-eliciting sounds were detectable in 30 cases out of 45. For ipsi- and bilateral stimulations, an attenuation was detectable for 7 guinea-pigs out of 10. In the guinea-pigs for which a reflex-induced change was found on CM, the mean attenuation was weak i.e. of the order of 2 dB at 20 dB above reflex threshold. These results were quite different from those obtained during control experiments in the rabbit for which CM attenuation was much larger. However, large attenuations associated with middle ear muscle contractions were found in the guinea-pig in other circumstances, i.e. during self-vocalization or when spontaneous muscle contractions occurred during anaesthesia. It is concluded that middle ear muscles can have several different functions, and that even when it exists, attenuation of loud sounds might not be their primary role. PMID- 1629048 TI - Enhancement and suppression in the auditory midbrain nucleus (MLD) of the pigeon. AB - Auditory evoked potentials (AEPs) and spike responses were recorded from the same recording site in the nucleus mesencephalicus lateralis pars dorsalis (MLD) in pigeons with a tungsten microelectrode. Depending on the recording sites within the MLD, enhancement and suppression of the AEPs in response to clicks were observed at particular frequencies of a background continuous pure tone. Post stimulus time histograms (PSTs) of the spike responses, if available in such cases, were recorded from the same position by the same electrode. Suppression of the AEPs always occurred but enhancement occurred in only 21% of the trials. The frequencies of tone bursts that caused maximum AEP were vaguely related to the frequencies of continuous pure tones that elicited maximum suppression of the AEPs in response to clicks. However, enhancement was produced by a continuous pure tone of approximately 1.5 kHz, independent of the frequencies of tone bursts that produced maximum AEPs. Most of the PSTs in such instances showed parallel relations between the spike responses and the amplitudes of the AEPs. The nature of the enhancement and suppression of the click evoked AEPs during continuous pure tones was clearly different from those in recordings from the nucleus magnocellularis, nucleus angularis and Field L in respect to the probability of occurrence of enhancement and suppression. PMID- 1629049 TI - Streptomycin blocks the afferent synapse of the isolated semicircular canals of the frog. AB - This study aimed to define the acute electrophysiological effects of the perilymphatic perfusion of streptomycin in the sensory apparatus of the semicircular canals of the frog. The ampullary DC potential, the vestibular nerve multiunit discharge, the nerve DC potential and the unitary EPSP activity were recorded in isolated semicircular canals of the frog (Rana esculenta L). The results demonstrated that perilymphatic microperfusion of streptomycin (0.1, 0.3, 1 and 3 mM) reduced both resting and mechanically evoked afferent discharge, while the response of the hair cells remains unchanged. Intracellular recordings from single afferent axons showed that the reduction of the afferent discharge was mainly due to a reduction of the amplitude, but not the frequency, of the EPSPs. These results indicate that streptomycin, when applied in the fluid bathing the synaptic pole of the sensory cells, can act as an antagonist of the vestibular afferent transmitter at the postsynaptic level. PMID- 1629050 TI - Effects of organic acids on the edema of the stria vascularis induced by furosemide. AB - Furosemide is a loop diuretic which is ototoxic. Investigations have shown the stria vascularis to be the target tissue of this ototoxic drug. The purpose of the present study was to investigate the effects of furosemide on the stria vascularis in chinchillas, in controls and in animals pretreated with the above organic acids. Control animals were injected with 0.5 ml alkalinized saline followed by furosemide IV 30 min later. Experimental animals received probenecid, penicillin or sodium salicylate IV. Thirty minutes later, furosemide was injected in the same dose as in the controls. The basal turn of the stria vascularis was rapidly removed at various times from 10 to 30 min after furosemide administration and processed for transmission electron microscopy. Control animals were found to have reversible edema of the stria vascularis. Experimental animals had variable findings. Those animals pretreated with penicillin had virtually no edema of the stria vascularis at any time. Salicylate and probenecid pretreated animals had significantly less edema from one to 10 min after furosemide injection, but more edema than controls at later times. These findings suggest a discrepancy between ultrastructural pathology and functional status of the cochlea in experimental animals pretreated with probenecid or sodium salicylate followed by furosemide. On the other hand, good structure function correlations were seen in controls and in experimental animals pretreated with penicillin. PMID- 1629051 TI - Spontaneous synaptic potentials from afferent terminals in the guinea pig cochlea. AB - Records of spontaneous activity from units likely to be radial afferents were analyzed to find the origin of spontaneous action potentials in single auditory nerve fibers. Single synaptic events (excitatory postsynaptic potentials or EPSPs) nearly all triggered action potentials (spikes). An abrupt increase in slope during the rising phase of the EPSP often signalled the initiation of an action potential. Synaptic potentials that did not trigger spikes occurred frequently during the refractory period. These events sometimes appeared to be composed of subunits. Refractoriness appears to be the primary reason these EPSPs were ineffective. Distributions of the onset slopes of postsynaptic potentials were highly skewed. Skewing was not a consequence of refractoriness, but most likely because the amplitude distribution of spontaneous potentials is not gaussian. PMID- 1629052 TI - Cochlear IgG in the C3H/lpr autoimmune strain mouse. AB - The inner ear of the C3H/lpr autoimmune strain mouse was evaluated to identify potential mechanisms by which systemic autoimmune disease interferes with auditory function. The inner ears were immunohistochemically stained for IgG at ages before (2 months) and after (6-10 months) autoimmune disease onset and compared to age-matched nonautoimmune C3H/HeJ controls. Immunoreactivity for IgG was not seen in the 2 month C3H/lpr autoimmune mice or in either age group of the C3H/HeJ controls. On the other hand, all older C3H/lpr mice showed reaction product in the vessels of the cochlea, particularly the stria vascularis and bony capsule. Less frequent sites of staining were the geniculate ganglion, marrow cavities of the bony capsule, tensor tympani muscle, and on one occasion, a hair cell of the organ of Corti. These findings indicate that IgG is widespread within the cochlea and its vessels during systemic autoimmune disease and not directed against any specific sensorineural structure. This suggests a generalized or indirect mechanism whereby such systemic disease affects the inner ear. PMID- 1629053 TI - American Society of Animal Science, Southern Section. 84th Annual Meeting. Lexington, Kentucky, February 2-5, 1992. Abstracts. PMID- 1629054 TI - You just can't find good help nowadays! PMID- 1629055 TI - Significance of plasma skimming and plasma volume expansion. AB - The organs associated with plasma volume expansion, i.e., the red bone marrow, the enlarged spleen, and the uteroplacental complex, are arteriovenous shunts with an interposed sinusoidal stroma able to skim off plasma-rich blood. In the spleen, plasma separation is an integral part of the hemoconcentration. In the red bone marrow, plasma skimming might provide a washout mechanism for the many newly formed erythrocytes and platelets from the sinusoids to the peripheral blood circulation. In the uteroplacental complex, skimming of plasma-rich blood is beneficial in increasing blood flow in the myometrium, kidneys, and skeletal musculature. The hypervolemic status with anemia will simulate a negative iron balance, which speeds up the absorption of iron. Thus a conceptual unit seems to exist in which rheological factors influence such functions as transport of newly formed blood cells into the circulation (in the red bone marrow), hemoconcentration (in the spleen), and iron balance during pregnancy (in the uteroplacental complex). PMID- 1629056 TI - Functional adaptations of rat skeletal muscle arterioles to aerobic exercise training. AB - This study tested the hypothesis that both structural and functional adaptations of arterioles occur within the skeletal muscle of rats aerobically trained for 8 10 wk with treadmill exercise. The training regimen used has been shown to elicit a 37% increase in plantaris citrate synthase activity but did not result in an elevation in citrate synthase activity in the spinotrapezius or gracilis muscles of rats used in this study. In the in vivo resting spinotrapezius muscle, arteriole diameters were similar in sedentary (SED) and trained (TR) rats. However, large- (1A) and intermediate- (2A) sized arterioles dilated proportionately more in TR than in SED rats during 1- to 8-Hz muscle contractions, even though the passive mechanical properties (circumference passive wall tension relationships) were similar between groups. Vascular casts demonstrated a trend for an increase in the number of small (3A) arterioles and an approximately 20% increase in the passive diameter of 1A and 2A arterioles in the spinotrapezius muscle of TR rats. In contrast, in the gracilis muscle, arteriole diameters and density were identical in SED and TR rats, but the capillary-to-muscle fiber ratio was approximately 15% higher in TR rats. The results suggest that aerobic exercise training can greatly increase functional vasodilation and induce a slight increase in vascular density in skeletal muscle tissues, even if the oxidative capacity of these tissues is not increased by the training regimen. PMID- 1629057 TI - Measurements of volume changes and venous pressure in the human lower leg during walking and running. AB - This study investigates whether walking or running prevents the formation of edema in the lower leg. In 18 volunteers changes in calf volume were measured using strain gauge plethysmography during slow (3 km/h) and fast (6 km/h) walking or running (10 km/h) on a treadmill for 20 min each. Venous pressure was measured in a superficial vein near the ankle. Low-pass filtering removed motion artifacts from the signals. Slow walking reduced the calf volume in a biphasic manner: a rapid decrease was followed by a slow decline, lasting from about minute 2 to minute 20, its mean rate being -0.073%/min. Besides a rapid initial decrease, no significant change was observed during fast walking. During running, the calf volume first increased within 7 min to a maximum of 2.5% and subsequently decreased with a mean rate of -0.096%/min. The medians of venous pressure were 84.0, 23.5, 30.4, and 29.5 mmHg during quiet standing, slow and fast walking, and running, respectively. The experimental results prove the hypothesis that walking prevents dependent edema formation. This effect, however, cannot be fully explained by the lowered venous pressures. PMID- 1629058 TI - Relationship between quasi-static pulmonary hysteresis and maximal airway narrowing in humans. AB - Two groups of subjects were studied: one with (group 1: 5 healthy and 4 mildly asthmatic subjects) and another without (group 2:9 moderately and severely asthmatic subjects) a plateau of response to methacholine (MCh). We determined the effect of deep inhalation by comparing expiratory flows at 40% of forced vital capacity from maximal and partial flow-volume curves (MEF40M/P) and the quasi-static transpulmonary pressure-volume (Ptp-V) area. In group 1, MEF40M/P increased from 1.58 +/- 0.23 (SE) at baseline up to a maximum of 3.91 +/- 0.69 after MCh when forced expiratory volume in 1 s (FEV1) was decreased on plateau by 24 +/- 2%. The plateau of FEV1 was always paralleled by a plateau of MEF40M/P. In group 2, MEF40 M/P increased from 1.58 +/- 0.10 at baseline up to a maximum of 3.48 +/- 0.26 after MCh when FEV1 was decreased by 31 +/- 3% and then decreased to 2.42 +/- 0.24 when FEV1 was decreased by 46 +/- 2%. Ptp-V area was similar in the two groups at baseline yet was increased by 122 +/- 9% in group 2 and unchanged in group 1 at MCh end point. These findings suggest that the increased maximal response to MCh in asthmatic subjects is associated with an involvement of the lung periphery. PMID- 1629059 TI - Spontaneous resolution of pulmonary edema caused by short periods of cyclic overinflation. AB - Mechanical ventilation with high or even moderate peak inspiratory pressure produces pulmonary permeability edema. Besides the level of overinflation, duration may affect both severity and type of edema. We studied the effect of 2 min of 35-mmHg peak pressure mechanical ventilation (HV) on microvascular permeability and deep lung fluid balance in rats. It resulted in increased extravascular lung water (+50%), bloodless dry lung weight (+25%), and albumin uptake in lungs (+450%). The increase in dry lung weight and albumin uptake compared with that of lung water suggested major permeability alterations. Ultrastructural examination showed the presence of numerous endothelial blebs. Epithelial lining fluid (ELF) volume, its potassium and protein concentrations, and cellular composition were assessed by bronchoalveolar lavage. There was an increase in ELF volume (+180%), a decrease in ELF potassium concentration (-50%), and an increase in ELF protein content (+76%). A few blood cells were recovered, suggesting the presence of a few large epithelial breaks. Some animals were allowed to recover for periods less than or equal to 180 min after HV. Extravascular lung water, dry lung weight, and albumin distribution space returned to control levels within 45 min. ELF volume diminished but remained larger than in controls, and ELF protein concentration increased probably because of alveolar fluid resorption. No further hemorrhage was observed. These results indicate that periods of HV as short as 2 min transiently alter microvascular permeability in rats. PMID- 1629061 TI - Thermoregulatory, cardiovascular, and psychophysical response to alcohol in men in 40 degrees C water. AB - The goals of the study were to test the hypotheses that ethyl alcohol (ETOH) in low-to-moderate doses would alter thermo-regulation and/or disrupt the normal relationship between physiological and psychophysical indexes of heat stress during 40 degrees C water immersion and to characterize the cardiovascular response to the combined stimuli of heat, water immersion, and ETOH. Six healthy men underwent three trials of 21 min of immersion in water at 40.0 +/- 0.1 degrees C after consuming 0, 0.27, or 0.54 g ETOH/kg. Esophageal temperature (Tes) rose by approximately 1.0 degrees C during immersion for each trial. Per unit of Tes rise, changes during immersion in skin temperature, sweat rate, heart rate, systolic and diastolic blood pressure, and psychophysical assessments of comfort and overheating did not differ significantly by trial. Across trials, there was an apparent threshold for activation of thermoregulatory responses at an approximately 0.5 degrees C increase in Tes occurring after approximately 9 min of immersion. This threshold was identified psychophysically by increased ratings of overheating and decreased comfort. Above the threshold, there was an attenuation of the rate of increase of Tes. Cardiovascular stress was mild (rate pressure product approximately 12,000) and not significantly increased by ETOH. Hypotension and tachycardia when subjects stood to exit the tub were observed. The data suggest that ETOH at the doses administered does not affect thermoregulatory, cardiovascular, or psychophysical indexes of heat stress during 40 degrees C water immersion. PMID- 1629062 TI - Rapidly alternating curvature ("oil canning") as a mechanism preventing alveolar edema. AB - This study has been designed to investigate the concept that the passage of red blood cells (clearly seen "bulging" into the air space in all scanning electron micrographs of the alveolar surface) can produce a net force tending to return any excess fluid to the interstitium. Measurements of surface tension over the time frame and probable surface area excursion incurred by a passing red blood cell show an appreciably higher value corresponding to the expanding surface, which is convex with respect to air, than when it is compressing and concave. The mean difference in surface tension of about 16 dyn/cm (mN/m) translates into a net driving force of approximately 6 mmHg induced by this rapidly alternating microcurvature reflecting the highly dynamic state of the living alveolar wall. The significance of the microcurvature of the alveolar surface is emphasized in relation to surfactant function. PMID- 1629060 TI - Bronchial vasodilation by histamine in sheep: characterization of receptor subtype. AB - Histamine has been shown to mediate features of pulmonary allergic reactions including increased tracheobronchial blood flow. To determine whether the increase in blood flow was due to stimulation of H1- or H2-histamine receptors, we gave histamine base (0.1 micrograms/kg iv) or histamine dihydrochloride as an aerosol (10 breaths of 0.5% "low dose" or 5% "high dose") before and after H1- or H2-receptor antagonists. Blood velocity in the common bronchial branch of the bronchoesophageal artery (Vbr) was continuously measured using a chronically implanted Doppler flow probe. Pretreatment with H2-receptor antagonists cimetidine, ranitidine, or metiamide did not affect the increase in Vbr induced by intravenous histamine [106 +/- 45% (SD)]. Addition of the H1-receptor antagonists diphenhydramine or chlorpheniramine, however, reduced the Vbr response to 16 +/- 22, 21 +/- 28, 23 +/- 23, and 37 +/- 32% of the unblocked responses (P less than 0.05) when intravenous histamine was given at 3, 10, 20, and 30 min, respectively, after the H1 antagonist. At 40, 50, and 60 min the H1 receptor blockade appeared to attenuate, but subsequent continuous infusion of chlorpheniramine (2 mg.kg-1.min-1) then blocked the histamine response for 60 min. Low-dose histamine aerosol did not change mean arterial or pulmonary arterial pressures, cardiac output, or arterial blood gases but increased Vbr transiently from 15.2 +/- 3.4 to 37.6 +/- 8.4 (SE) cm/s. After chlorpheniramine, the Vbr response to histamine, 16.3 +/- 2.2 to 22.6 +/- 3.6 cm/s, was significantly reduced (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629063 TI - Diurnal variations in serum erythropoietin levels in healthy subjects and sleep apnea patients. AB - We measured arterial oxygen saturation (SaO2) and serum erythropoietin (EPO) levels in patients with obstructive sleep apnea syndrome (OSAS) and in healthy subjects. SaO2 profile was analyzed as the cumulative distribution of SaO2 over time. OSAS patients spent 25.5 +/- 30.9% (SD) of the time at SaO2 of less than 88% vs. 0.64 +/- 1.6% in healthy subjects (P less than 0.05) and had 59 +/- 25 desaturations (greater than 4%) per hour vs. less than 5 per hour in healthy subjects (P less than 0.05). EPO measurements (radioimmunoassay) were made in blood samples withdrawn every 1 or 2 h over a 24-h period. The mean EPO concentration was higher (P less than 0.05) for OSAS patients (45 +/- 33 mU/ml) than for normal subjects (17 +/- 8 mU/ml). There was a significant variability in EPO values over the 24-h period. To analyze the EPO pattern over 24 h, EPO time series were fit to a general cosine function. Data from normal subjects conformed to a cosine function with an amplitude of 3.5 +/- 2.1 (CV of 60%) and an acrophase of 1,000 +/- 184 min after 0800 (CV of 18%), indicating a zenith about 1 A.M. and a nadir around 1 P.M. Data from OSAS subjects fit a similar cosine function with an amplitude of 19.9 +/- 41.0 (CV of 206%) and acrophase of 582 +/- 408 min (CV of 70%), indicating a greater variability in the magnitude and the timing of peak serum EPO levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629064 TI - Pulmonary vascular impedance and wave reflections in the hypoxic calf. AB - The alterations in pulsatile hemodynamics that occur during hypoxic pulmonary vasoconstriction have not been well characterized. Changes in oscillatory hemodynamics, however, may affect right ventricular-pulmonary vascular coupling and the dissipation of energy within the lung vasculature. To better define hypoxic pulsatile hemodynamics, we measured main pulmonary artery proximal and distal micromanometric pressures and ultrasonic flow in four open-chest calves during progressive hypoxia. Main pulmonary artery impedance and pressure transmission spectra were calculated using spectral analysis methods. Measured pressure and flow signals were separated in the time domain into forward and backward components. Hypoxia increased pulmonary blood pressure and resistance and produced multiple modifications in the impedance and pressure transmission spectra that indicated increased wave reflections and elasticity. The impedance and apparent phase velocity first-harmonic values were increased in amplitude, and the pressure transmission modulus plot showed an increased peak value. In addition, the impedance modulus plot demonstrated a rightward shift and increased oscillation in the mid- to high-frequency range. The time domain analysis also confirmed increased wave reflections and elasticity. Hypoxia produced large backward-traveling (reflected) pressure and flow waves. The initial portions of these waves arrived at the heart during systole, producing characteristic changes in the measured pressure and flow waveforms. With prolonged hypoxia, main pulmonary artery pulse wave velocity increased by 30%. Thus, hypoxia is associated with complex alterations in pulmonary artery elasticity and wave reflections that act to increase the oscillatory afterload of the right ventricle. PMID- 1629065 TI - Influence of airway resistance on hypoxia-induced periodic breathing. AB - We studied the effects of changing upper airway pressure on the variability of the dynamic response of ventilation to a hypoxic disturbance in 11 spontaneously breathing dogs. Supralaryngeal pressure, instantaneous inspiratory flow, end expiratory lung volume, and the inspiratory and expiratory O2 and CO2 concentrations were continuously recorded at baseline and after a 1.5-min hypoxic stimulus (abrupt normoxic recovery). Arterial blood gases were obtained at baseline, at the end of the hypoxic period, and after 1 min of recovery. Airway resistances were modified during the recovery by changing the composition of the inspired gas (all with an inspiratory O2 fraction of 20.9%) among four different trials: two trials were realized with air (density 1.12 g/l), and the other two were with He or SF6 (respective density 0.42 and 4.20) in random order. There was no difference between baseline minute ventilation, arterial blood gases, and supralaryngeal resistance values preceding the trials. The hypoxemic and hypocapnic levels and the hypoxia-induced hyperventilation reached during the hypoxic tests were identical for the different hypoxic stimuli. The supralaryngeal resistance measured at peak flow was dramatically influenced by the composition of the inspired gas: 8.8 +/- 1.8 and 6.9 +/- 1.7 (SE) cmH2O.l-1.s with air, 7.2 +/- 2.2 with He, 21.9 +/- 5.5 with SF6 (P less than 0.05). Ventilatory fluctuations were consistently seen during the posthypoxic period. They were characterized by a strength index value (M) (Waggener et al. J. Appl. Physiol. 56: 576-581, 1984).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629066 TI - Human cold air habituation is independent of thyroxine and thyrotropin. AB - Thyroxine (T4) is required in species possessing brown adipose tissue (BAT) for the maintenance of cold tolerance and adaptation. In humans, who possess negligible quantities of BAT, the importance of T4 has not been demonstrated. We studied the effects of decreased serum T4 and thyrotropin (TSH) on human cold habituation after repeated cold air exposures. Eight men (T3+) received a single daily dose of triiodothyronine (T3; 30 micrograms/day), and another eight men (T3 ) received a placebo. All 16 normal thyroid men underwent a standardized cold air test (SCAT) under basal conditions in January and again in March after eighty 30 min 4.4 degrees C air exposures (10/wk). Measurements of basal metabolic rate (BMR), O2 consumption (VO2), mean arterial pressure (MAP), plasma norepinephrine (NE), serum TSH, free and total T4, and free and total T3 were repeated before and after 8 wk of exposure. TSH, free T4, and total T4 were 50% lower for T3+ than for T3- subjects. Total and free T3 were not different between groups. BMR was unchanged after habituation, whereas the cold-stimulated VO2, MAP, and NE were significantly reduced for all subjects in March. The relationship between VO2 and NE (r2 = 0.44, P less than 0.001) during the initial SCAT was unchanged with habituation. We suggest that human cold habituation is independent of major changes in circulating T4 and TSH. PMID- 1629067 TI - Anesthetic effects on pulmonary allergic responses in rats: changes in sensitivity to serotonin. AB - Subsequent to observations that pulmonary responses to antigen challenge are of different magnitudes in sensitized rats that are anesthetized with different drugs, we conducted studies to test whether the alterations in responses were due to changes in airway responsiveness to cholinergic or serotonergic challenge, opioid-receptor mediated events, or changes in mast cell mediator release. Immunoglobulin E-sensitized rats anesthetized with ketamine/urethan had larger changes in lung resistance and plasma histamine after pulmonary antigen challenge compared with rats anesthetized with fentanyl-droperidol. Blockade of opioid receptors with naloxone did not affect the responses. In unsensitized rats, airway responses to aerosolized methacholine were similar for the two anesthetics, indicating unchanged smooth muscle responsiveness; however, airway responses to intravenous serotonin were enhanced by ketamine and ablated by droperidol. We conclude that ketamine- and droperidol-induced alterations of pulmonary allergic responses are due to changes in sensitivity to serotonin and in mast cell mediator release. We speculate that mast cell mediator release may be modulated by a serotonin receptor-linked mechanism. PMID- 1629068 TI - Antagonists of EDRF attenuate acetylcholine-induced vasodilation in isolated hamster lungs. AB - To evaluate the role of endothelium-dependent relaxing factor (EDRF) in acetylcholine- (ACh) induced vasodilation in the intact pulmonary circulation, we examined the effects of atropine and three EDRF antagonists that have been shown to be effective in vitro: nitro-L-arginine (NOARG), hemoglobin (Hb), and methylene blue (MB). We studied ACh-induced dilation after preconstriction with angiotensin II and prostaglandin F2 alpha (PGF2 alpha) in hamster lungs perfused with Krebs solution containing Ficoll (4 g/dl) and indomethacin (10 microM). In the constricted lungs with no blockers, infusion of ACh (1 microM) decreased the constriction by 67%, and this effect was completely abolished by atropine pretreatment (1 microM). Treatment of hamster lungs with each of the three EDRF blockers, NOARG (30 microM), Hb (10 microM), and MB (250 microM), augmented the pressor responses to angiotensin II and PGF2 alpha. However, NOARG and MB inhibited the ACh-induced dilation by 49 and 60%, respectively, without affecting vasodilatory responses to isoproterenol, an agent that relaxes vascular smooth muscle independent of EDRF synthesis. In contrast, Hb significantly inhibited both ACh- and isoproterenol-induced vasodilations. Because all these EDRF antagonists attenuated ACh-induced vasodilation in intact hamster lungs, we conclude that EDRF plays a role in this response. Nonselective inhibitory effects of Hb in hamster lungs, however, suggest that mechanisms other than inhibition of EDRF by this agent are also involved. PMID- 1629069 TI - Elevated muscle vitamin E does not attenuate eccentric exercise-induced muscle injury. AB - The purpose of this study was to evaluate the effect of elevated muscle vitamin E content on skeletal muscle damage from eccentric exercise. Sixty Sprague-Dawley rats were put on a normal (40 IU vitamin E/kg food) or supplemented (10,000 IU vitamin E/kg food) diet for 5 wk. Injury in soleus muscle was determined using several criteria: reductions in maximal tetanic force and number of intact fibers per square millimeter and elevations in muscle glucose 6-phosphate dehydrogenase activity and plasma creatine kinase activity, either immediately (0 h) or 2 days (48 h) after a downhill walking protocol. Sedentary animals were also tested but did not exercise. Muscle vitamin E levels were significantly elevated (approximately 3- to 4-fold), and susceptibility of the muscles to oxidant stress was decreased, after supplementation. However, vitamin E supplementation did not attenuate injury by any of the criteria employed. Maximal tetanic force decreased approximately 20% at 0 and 48 h after exercise in both groups. The number of intact fibers per square millimeter decreased approximately 30-35% in both groups at 0 and 48 h. Glucose 6-phosphate dehydrogenase activity increased approximately 50-100% in both groups at 48 h, and plasma creatine kinase activity was elevated approximately 2- to 2.5-fold at 0 h in both groups. These findings do not support a major role for free radical damage to muscle membranes in the initiation of injury from eccentric exercise, although they do not disprove free radical involvement in the etiology. PMID- 1629070 TI - Extracorporeal circulation in the isolated in situ lamb placenta: hemodynamic characteristics. AB - Decreased placental perfusion and respiratory gas exchange have been observed after experimental fetal cardiopulmonary bypass (CPB). To better characterize placental hemodynamics during CPB, seven isolated in situ lamb placentas were placed on a CPB circuit by use of umbilical arterial and venous cannulation. Measures were taken to simulate normal placental hemodynamics. Perfusion flow rates were varied from 15 to 300 ml.min-1.kg fetal wt-1 during normothermia and hypothermia. Placental vascular resistance (PVR) remained constant when perfusion pressure and flow were varied above 40 mmHg and 150 ml.min-1.kg-1, respectively. Below these values, PVR varied inversely. This increase in PVR was more marked when CPB was performed with hypothermia than with normothermia. The clinical implication is that decreased placental flow and pressure on CPB may lead to a vicious cycle, resulting in further impairment of placental perfusion and respiratory gas exchange. Hypothermia promotes this impairment. PMID- 1629071 TI - Use of bioelectrical impedance to assess body composition changes at high altitude. AB - This study determined the feasibility of using bioelectrical impedance analysis (BIA) to assess body composition alterations associated with body weight (BW) loss at high altitude. The BIA method was also evaluated relative to anthropometric assessments. Height, BW, BIA, skinfold (SF, 6 sites), and circumference (CIR, 5 sites) measurements were obtained from 16 males (23-35 yr) before, during, and after 16 days of residence at 3,700-4,300 m. Hydrostatic weighings (HW) were performed pre- and postaltitude. Results of 13 previously derived prediction equations using various combinations of height, BW, age, BIA, SF, or CIR measurements as independent variables to predict fat-free mass (FFM), fat mass (FM), and percent body fat (%Fat) were compared with HW. Mean BW decreased from 84.74 to 78.84 kg (P less than 0.01). As determined by HW, FFM decreased by 2.44 kg (P less than 0.01), FM by 3.46 kg (P less than 0.01), and %Fat by 3.02% (P less than 0.01). The BIA and SF methods overestimated the loss in FFM and underestimated the losses in FM and %Fat (P less than 0.01). Only the equations utilizing the CIR measurements did not differ from HW values for changes in FFM, FM, and %Fat. It was concluded that the BIA and SF methods were not acceptable for assessing body composition changes at altitude. PMID- 1629072 TI - Endurance training amplifies the pulsatile release of growth hormone: effects of training intensity. AB - The effects of intensity of run training on the pulsatile release of growth hormone (GH) were investigated in 21 eumenorrheic untrained women. The O2 consumption (VO2) at the lactate threshold (LT); fixed blood lactate concentrations (FBLC) of 2.0, 2.5, and 4.0 mM; peak VO2; maximal VO2; body composition; and pulsatile release of GH were measured. Subjects in both the at lactate threshold (/LT, n = 9) and above-lactate threshold (greater than LT, n = 7) training groups increased VO2 at LT and FBLC of 2.0, 2.5, and 4.0 mM and VO2max after 1 yr of run training. However, the increase observed in the greater than LT group was greater than that in the /LT group (P less than 0.05). No change was observed for the control group (n = 5). No among- or within-group differences were observed for body weight, although trends for reductions in percent body fat (P less than 0.06) and fat weight (P less than 0.15) were observed in the greater than LT group, and both training groups significantly increased fat-free weight (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629073 TI - Eccentric exercise induces transient insulin resistance in healthy individuals. AB - Euglycemic-hyperinsulinemic clamps were performed on six healthy untrained individuals to determine whether exercise that induces muscle damage also results in insulin resistance. Clamps were performed 48 h after bouts of predominantly 1) eccentric exercise [30 min, downhill running, -17% grade, 60 +/- 2% maximal O2 consumption (VO2max)], 2) concentric exercise (30 min, cycle ergometry, 60 +/- 2% VO2max), or 3) without prior exercise. During the clamps, euglycemia was maintained at 90 mg/dl while insulin was infused at 30 mU.m-2.min-1 for 120 min. Hepatic glucose output (HGO) was determined using [6,6-2H]glucose. Eccentric exercise caused marked muscle soreness and significantly elevated creatine kinase levels (273 +/- 73, 92 +/- 27, 87 +/- 25 IU/l for the eccentric, concentric, and control conditions, respectively) 48 h after exercise. Insulin-mediated glucose disposal rate was significantly impaired (P less than 0.05) during the clamp performed after eccentric exercise (3.47 +/- 0.51 mg.kg-1.min-1) compared with the clamps performed after concentric exercise (5.55 +/- 0.94 mg.kg-1.min-1) or control conditions (5.48 +/- 1.0 mg.kg-1.min-1). HGO was not significantly different among conditions (0.77 +/- 0.26, 0.65 +/- 0.27, and 0.66 +/- 0.64 mg.kg 1.min-1 for the eccentric, concentric, and control clamps, respectively). The insulin resistance observed after eccentric exercise could not be attributed to altered plasma cortisol, glucagon, or catecholamine concentrations. Likewise, no differences were observed in serum free fatty acids, glycerol, lactate, beta hydroxybutyrate, or alanine. These results show that exercise that results in muscle damage, as reflected in muscle soreness and enzyme leakage, is followed by a period of insulin resistance. PMID- 1629074 TI - Effect of prior exercise and insulin on potential thermogenic systems in rat skeletal muscle. AB - We previously reported that insulin stimulates oxygen consumption by the perfused rat hindquarter after high-intensity exercise. The purpose of the present study was to examine whether fructose 6-phosphate-fructose 1,6-bisphosphate cycling or an uncoupling of mitochondrial respiration contributes to this phenomenon. Hindquarter skeletal muscle was analyzed after perfusion in the absence or presence of insulin (150-200 microU/ml) for high-energy phosphate content, fructose 6-phosphate-fructose 1,6-bisphosphate cycling of glucose before incorporation into glycogen, and mitochondrial respiratory control. Muscle from exercised rats perfused with insulin did not display greater rates of glucose cycling or mitochondrial uncoupling; in fact, insulin decreased the rate of fructose 6-phosphate cycling and tended to increase respiratory control in skeletal muscle mitochondria. In addition, the concentrations of ATP and creatine phosphate and the calculated free ADP level in muscle of previously exercised rats perfused with insulin were similar to those of control rats. The results do not exclude the possibility that localized subcellular changes in ADP occurred, however. In conclusion, the results suggest that insulin-induced increases in other substrate cycles, ion transport systems, and/or as yet unidentified energy requiring processes account for the 25-30% increase in hindquarter oxygen consumption after intense exercise. PMID- 1629075 TI - Effect of hindlimb unweighting on tissue blood flow in the rat. AB - The purpose of this study was to characterize the distribution of blood flow in the rat during hindlimb unweighting (HU) and post-HU standing and exercise and examine whether the previously reported (Witzmann et al., J. Appl. Physiol. 54: 1242-1248, 1983) elevation in anaerobic metabolism observed with contractile activity in the atrophied soleus muscle was caused by a reduced hindlimb blood flow. After either 15 days of HU or cage control, blood flow was measured with radioactive microspheres during unweighting, normal standing, and running on a treadmill (15 m/min). In another group of control and experimental animals, blood flow was measured during preexercise (PE) treadmill standing and treadmill running (15 m/min). Soleus muscle blood flow was not different between groups during unweighting, PE standing, and running at 15 m/min. Chronic unweighting resulted in the tendency for greater blood flow to muscles composed of predominantly fast-twitch glycolytic fibers. With exercise, blood flow to visceral organs was reduced compared with PE values in the control rats, whereas flow to visceral organs in 15-day HU animals was unaltered by exercise. These higher flows to the viscera and to muscles composed of predominantly fast-twitch glycolytic fibers suggest an apparent reduction in the ability of the sympathetic nervous system to distribute cardiac output after chronic HU. In conclusion, because 15 days of HU did not affect blood flow to the soleus during exercise, the increased dependence of the atrophied soleus on anerobic energy production during contractile activity cannot be explained by a reduced muscle blood flow. PMID- 1629076 TI - In vivo effects of Escherichia coli endotoxemia on diaphragmatic microcirculation in rats. AB - We investigated the effects of Escherichia coli endotoxin administration on diaphragmatic microcirculation in rats by in vivo videomicroscopy. Rats were allocated into three groups: 1) intravenous inoculation of 10 mg/kg of E. col endotoxin (group E, n = 25), 2) intravenous inoculation of sterile 0.9% NaCl (group C, n = 20), and 3) induction of a controlled hemorrhage by reducing the vascular volume via an arterial catheter (group H, n = 15). Mean blood pressure (BP) and arteriolar diameters were measured at 15-min intervals and capillary perfusion pattern at 30-min intervals for 1 h. BP decreased similarly in groups E and H, whereas it was maintained in group C. Arterioles were classified as second (A2, n = 46), third (A3, n = 22), and fourth (A4, n = 21) order, according to their relative localization in the network. Basal diameters were the same in the three groups: 38.16, 17.33, and 6.80 microns in group C; 38.17, 17.41, and 7.04 microns in group E; and 37.82, 19.19, and 6.99 microns in group H for A2, A3, and A4, respectively. During the observation period, a significant and similar vasoconstriction of A2 arterioles was observed in groups E and H but not in group C. By contrast, in the three groups, no significant changes in diameter were found for the A3 and A4 arterioles. Capillary perfusion was markedly impaired in group E: at 60 min the percentage of non-perfused capillaries was 40.92 +/- 6.65% in group E compared with 21.17 +/- 5.45% in group C (P less than 0.05) and 18.18 +/- 8.11% in group H (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629077 TI - A fractal continuum model of the pulmonary arterial tree. AB - The extant morphometric data from the intrapulmonary arteries of dog, human, and cat lungs produce graphs of the log of the vessel number, (N) or length (l) in each level vs. the log of the mean diameter (D) in each level that are sufficiently linear to suggest that a scale-independent self-similar or fractal structure may underlie the observed relationships. These data can be correlated by the following formulas: Nj = a1Dj-beta 1, and lj = a2Dj beta 2, where j denotes the level (order or generation) number measured from the largest vessel at the entrance to the arterial tree to the smallest vessel at the entrance to the capillary bed. With the hemodynamic resistance (R) represented by Rj = 128 microliterj/(Nj pi Dj4) and the vascular volume (Q) by Qj = Nj pi Dj2lj/4, the continuous cumulative distribution of vascular resistance (Rcum) vs. cumulative vascular volume (Qcum) (where Rcum and Qcum represent the total resistance or volume, respectively, upstream from the jth level) can be calculated from [formula: see text] where r = Dj/Dj+1 is a constant independent of j. Analogous equations are developed for the inertance and compliance distributions, providing simple formulas to represent the hemodynamic consequences of the pulmonary arterial tree structure. PMID- 1629078 TI - Brain adaptation to chronic hypobaric hypoxia in rats. AB - Rats were exposed to hypobaric hypoxia (0.5 atm) for up to 3 wk. Hypoxic rats failed to gain weight but maintained normal brain water and ion content. Blood hematocrit was increased by 48% to a level of 71% after 3 wk of hypoxia compared with littermate controls. Brain blood flow was increased by an average of 38% in rats exposed to 15 min of 10% normobaric oxygen and by 23% after 3 h but was not different from normobaric normoxic rats after 3 wk of hypoxia. Sucrose space, as a measure of brain plasma volume, was not changed under any hypoxic conditions. The mean brain microvessel density was increased by 76% in the frontopolar cerebral cortex, 46% in the frontal motor cortex, 54% in the frontal sensory cortex, 65% in the parietal motor cortex, 68% in the parietal sensory cortex, 68% in the hippocampal CA1 region, 57% in the hippocampal CA3 region, 26% in the striatum, and 56% in the cerebellum. The results indicate that hypoxia elicits three main responses that affect brain oxygen availability. The acute effect of hypoxia is an increase in regional blood flow, which returns to control levels on continued hypoxic exposure. Longer-term effects of continued moderate hypoxic exposure are erythropoiesis and a decrease in intercapillary distance as a result of angiogenesis. The rise in hematocrit and the increase in microvessel density together increase oxygen availability to the brain to within normal limits, although this does not imply that tissue PO2 is restored to normal. PMID- 1629079 TI - Dynamics of ventilation, circulation, and gas exchange to incremental and decremental ramp exercise. AB - Transient responses of minute volume (VE), O2 uptake (VO2), CO2 output (VCO2), heart rate (HR), and cardiac output (Q) to a step change and ramp changes with slopes ranging from 33.3 to 14.3 W/min were studied in five healthy human subjects over the load range from 25 to 125 W. The ramp responses were fitted to a first-order model with a pure time delay (td) and a time constant (TC), while most of the step responses fitted better to a second-order model, consisting of a fast and a slow component. No significant asymmetry was observed between the on- and off-responses to step forcing. The mean response time (MRT = td+TC) of the incremental ramp response was prolonged, whereas the MRT of the decremental ramp response was shortened or unchanged, with decreasing ramp slope. The asymmetry was commonly observed in respiratory and gas exchange variables and, to a lesser extent, also in circulatory variables. Neural and humoral factors that might be responsible for this phenomenon are discussed. PMID- 1629080 TI - Effect of aspartic acid on control of ventilation in androgenized and ovariectomized female rats. AB - Previously we observed that acute subcutaneous administration of aspartic acid (580 mg/kg) depressed ventilation in awake male, but not female, rats, suggesting that this agent may be used as a marker for sexual dimorphism in the control of ventilation. Moreover, males castrated postpubertally showed a response similar to that of intact male rats. Thus the hormonal milieu of male rats appear not to be necessary to elicit the masculine type of ventilatory response to aspartic acid. The purpose of this study was 1) to determine whether adult female rats androgenized by the administration of testosterone propionate (TP) 1 day after birth would alter their ventilation in response to aspartic acid to be more malelike and 2) to compare these results with those of intact (I) and ovariectomized (O) female rats. Minute ventilation and O2 consumption in air and in response to aspartic acid administration were evaluated in awake animals in all three groups. Furthermore the minute ventilation of all rats to a hypercapnic challenge was also evaluated. Ovariectomy resulted in rats increased body weights but decreased weight-corrected ventilation and O2 consumption compared with TP treated and I animals. Minute ventilation after hypercapnic challenge in the three groups was similar. TP-treated rats responded to aspartic acid administration with a marked depression of ventilation similar to that previously noted in males, whereas neither I nor O rats showed such a response. The depression of ventilation in the TP-treated group in response to aspartic acid was not a consequence of a depression of O2 consumption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629081 TI - Intracellular pH and oxygen chemoreception in the cat carotid body in vitro. AB - To test the hypothesis that O2 chemoreception in the carotid body (CB) is mediated by cellular acidosis, we simultaneously measured responses of the chemosensory and intracellular pH (pHi) to agents that are known to change pHi and studied the effects of hypoxia and ischemia on these variables in the cat CB. The CB was perfused and superfused in vitro with a modified Tyrode's solution at 36.0 +/- 0.5 degrees C with or without CO2-HCO3- (pH 7.40) and equilibrated at a given PO2. Chemosensory discharges were recorded from the whole carotid sinus nerve. To measure pHi changes, the CB was loaded with the pH-sensitive indicator 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, and the fluorescence (excitation 420-490 nm, emission greater than 515 nm) was detected by an intensified charged coupled device camera with an epifluorescence macroscope. Boluses of Tyrode's solution (0.5 ml, free of CO2-HCO3-) containing sodium acetate or NH4Cl prolonged perfusion of acid Tyrode's solution (pH 7.20-6.50), and boluses of Tyrode's solution with CO2-HCO3- were used. A decrease of fluorescence indicated pHi turning acid, and an increase of fluorescence indicated a change in alkaline pHi. Chemosensory activity varied inversely with the fluorescence change after application of these agents. Interruption of perfusate flow or application of hypoxic perfusate resulted in large increases in chemosensory discharge without any change in the fluorescence. The results indicated that chemosensory responses to brief ischemia and hypoxia were not mediated by a fall of pHi of CB cells, whereas those to CO2 and extracellular acidity were associated with decreases in pHi. PMID- 1629082 TI - Mechanism of detection of resistive loads in conscious humans. AB - Conscious humans easily detect loads applied to the respiratory system. Resistive loads as small as 0.5 cmH2O.l-1.s can be detected. Previous work suggested that afferent information from the chest wall served as the primary source of information for load detection, but the evidence for this was not convincing, and we recently reported that the chest wall was a relatively poor detector for applied elastic loads. Using the same setup of a loading device and body cast, we sought resistive load detection thresholds under three conditions: 1) loading of the total respiratory system, 2) loading such that the chest wall was protected from the load but airway and intrathoracic pressures experienced negative pressure in proportion to inspiratory flow, and 3) loading of the chest wall alone with no alteration of airway or intrathoracic pressure. The threshold for detection for the three types of load application in seven normal subjects was 1.17 +/- 0.33, 1.68 +/- 0.45, and 6.3 +/- 1.38 (SE) cmH2O.l-1.s for total respiratory system, chest wall protected, and chest wall alone, respectively. We conclude that the active chest wall is a less potent source of information for detection of applied resistive loads than structures affected by negative airway and intrathoracic pressure, a finding similar to that previously reported for elastic load detection. PMID- 1629084 TI - Dependence of muscle fatigue on stimulation protocol: effect of hypocaloric diet. AB - This study tested the hypothesis that the decreased resistance of skeletal muscles to fatigue after a period of inadequate nutrition is a consequence of the type of fatigue test employed. Rats (n = 8) were fed hypocalorically for 10 days, resulting in a 33.5 +/- 3.0% (SE) reduction in body weight. The fatigue resistance of muscles was assessed with use of isolated soleus muscles at a temperature of 25 degrees C. Fatigue resistance was determined from the decline in isometric force during a series of tetanic contractions. Two contrasting contraction protocols were devised to test the susceptibility of muscles to fatigue. One protocol was designed to require high rates of energy supply and hence force a dependence on glycolytic energy supply pathways. The second protocol required much lower rates of energy supply that could be entirely met by oxidative energy supply processes. During the high energy demand (glycolytic) protocol, the force produced by muscles from a control group of rats decreased to 78.7 +/- 0.8% (n = 12 muscles) of the initial value. Hypocaloric feeding significantly reduced the resistance of muscles to fatigue: force declined to 61.3 +/- 3.5% (n = 16 muscles) during the contraction protocol. In contrast, when fatigue was quantified using the low energy demand (oxidative) contraction protocol, the effect of nutritional status on fatigue resistance was entirely abolished. This result supports the hypothesis that resistance to fatigue is critically dependent on the fatigue test employed. PMID- 1629083 TI - Effect of Pseudomonas aeruginosa rhamnolipids on mucociliary transport and ciliary beating. AB - Pseudomonas aeruginosa rhamnolipid causes ciliostasis and cell membrane damage to rabbit tissue, is a secretagogue in cats, and inhibits epithelial ion transport in sheep tissue. It could therefore perturb mucociliary clearance. We have investigated the effect of rhamnolipid on mucociliary transport in the anesthetized guinea pig and guinea pig and human respiratory epithelium in vitro. Application of rhamnolipid to the guinea pig tracheal mucosa reduced tracheal mucus velocity (TMV) in vivo in a dose-dependent manner: a 10-microgram bolus caused cessation of TMV without recovery; a 5-micrograms bolus reduced TMV over a period of 2 h by 22.6% (P = 0.037); a 2.5-microgram bolus caused no overall changes in TMV. The ultrastructure of guinea pig tracheal epithelium exposed to 10 micrograms of rhamnolipid in vivo was normal. Application of 1,000 micrograms/ml rhamnolipid had no effect on the ciliary beat frequency (CBF) of guinea pig tracheal rings in vitro after 30 min, but 250 micrograms/ml stopped ciliary beating after 3 h. Treatment with 100 micrograms/ml rhamnolipid caused immediate slowing of the CBF (P less than 0.01) of human nasal brushings (n = 7), which was maintained for 4 h. Mono- and dirhamnolipid had equivalent effects. The CBF of human nasal turbinate organ culture was also slowed by 100 micrograms/ml rhamnolipid, but only after 4 h (CBF test, 9.87 +/- 0.41 Hz; control, 11.48 +/- 0.27 Hz; P less than 0.05, n = 6), and there was subsequent recovery by 14 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629085 TI - Electrical activation of expiratory muscles increases with time in pentobarbital anesthetized dogs. AB - Although the pentobarbital-anesthetized dog is often used as a model in studies of respiratory muscle activity during spontaneous breathing, there is no information regarding the stability of the pattern of breathing of this model over time. The electromyograms of several inspiratory and expiratory muscle groups were measured in six dogs over a 4-h period by use of chronically implanted electrodes. Anesthesia was induced with pentobarbital sodium (25 mg/kg iv), with supplemental doses to maintain constant plasma pentobarbital concentrations. Phasic electrical activity increased over time in the triangularis sterni, transversus abdominis, and external oblique muscles (expiratory muscles). The electrical activity of the costal diaphragm, crural diaphragm, and parasternal intercostal muscles (inspiratory muscles) was unchanged. These changes in electrical activity occurred despite stable plasma levels of pentobarbital and arterial PCO2. They were associated with changes in chest wall motion and an increased tidal volume with unchanged breathing frequency. We conclude that expiratory muscle groups are selectively activated with time in pentobarbital-anesthetized dogs lying supine. Therefore the duration of anesthesia is an important variable in studies using this model. PMID- 1629086 TI - Effects of pharyngeal lubrication on the opening of obstructed upper airway. AB - We examined the effect of electrical stimulation of the hypoglossal nerve and pharyngeal lubrication with artificial surfactant (Surfactant T-A) on the opening of obstructed upper airway in nine anesthetized supine dogs. The upper airway was isolated from the lower airway by transecting the cervical trachea. Upper airway obstruction was induced by applying constant negative pressures (5, 10, 20, and 30 cmH2O) on the rostral cut end of the trachea. Peripheral cut ends of the hypoglossal nerves were electrically stimulated by square-wave pulses at various frequencies from 10 to 30 Hz (0.2-ms duration, 5-7 V), and the critical stimulating frequency necessary for opening the obstructed upper airway was measured at each driving pressure before and after pharyngeal lubrication with artificial surfactant. The critical stimulation frequency for upper airway opening significantly increased as upper airway pressure became more negative and significantly decreased with lubrication of the upper airway. These findings suggest that greater muscle tone of the genioglossus is needed to open the occluded upper airway with larger negative intraluminal pressure and that lubrication of the pharyngeal mucosa with artificial surfactant facilitates reopening of the upper airway. PMID- 1629087 TI - Alterations in diaphragmatic oxidative and antioxidant enzymes in the senescent Fischer 344 rat. AB - We investigated age-related changes in antioxidant, glycolytic, beta-oxidation, and tricarboxylic acid cycle enzyme activity in the diaphragm and plantaris muscle of female Fischer 344 rats. Tissue samples from the costal and crural diaphragm and plantaris muscle were obtained from 30 animals in the following age groups: 1) 6 mo old (n = 10), 2) 26 mo old (n = 10), and 3) 30 mo old (n = 10). Aging had no effect (P greater than 0.05) on the activities of citrate synthase (CS) and 3-hydroxyacyl-CoA dehydrogenase (HADH) in the costal or crural diaphragm. Similarly, no age-related differences existed (P greater than 0.05) in the crural diaphragm in lactate dehydrogenase (LDH) or glutathione peroxidase (GPX) activity. In contrast, the activities of LDH and GPX were significantly (P less than 0.05) higher in the costal diaphragm in the 30- than in the 6-mo old animals. In addition, the ratio of LDH to CS activity increased (P less than 0.05) as a function of age in the costal diaphragm. Conversely, the ratio of CS to GPX activity in the costal diaphragm was lower (P less than 0.05) in the 30- than in the 6-mo old animals. No significant (P greater than 0.05) age-related differences existed in LDH-to-CS or CS-to-GPX activity ratios in the crural diaphragm. Finally, aging resulted in a significant decrease (P less than 0.05) in the activities of LDH, CS, and HADH in the plantaris muscle. These data demonstrate that, unlike many hindlimb locomotor muscles, the oxidative capacity of the Fischer 344 rat diaphragm does not decrease in old age. PMID- 1629088 TI - Effects of cricothyroid muscle contraction on upper airway flow dynamics in dogs. AB - We studied the effects of cricothyroid muscle (CT) contraction on upper airway flow dynamics in eight prone open-mouth anesthetized dogs. Animals were mechanically ventilated via a tracheostomy while a constant airflow (Vuaw) passed through the isolated upper airway. Nasal airflow (Vn) was monitored using a nasal mask and pneumotachograph. Bilateral CT contraction was induced by electrical stimulation of the external branches of the superior laryngeal nerves. During CT contraction with Vuaw of 100-443 ml/s in the inspiratory direction, total upper airway resistance (Ruaw) fell by 49.1 +/- 5.4% (SE) while supraglottic resistance fell by 63.6 +/- 3.6%; simultaneously Vn fell by 55.3 +/- 3.8% and Vuaw increased by 7.2 +/- 1.7%. Similar results were obtained when Vuaw was in the expiratory direction. In three dogs in which the attachments of the CT to either the thyroid or cricoid cartilage were severed, superior laryngeal nerve stimulation had no systematic effect on Ruaw. Because visual assessment during CT contraction consistently revealed dilation of the piriform recesses, we suggest that CT contraction is associated with pharyngeal dilation, which in open-mouth dogs (with overlapping soft palate and epiglottis) redistributes flow to the oral route with a net reduction in Ruaw. Thus the CT may have a respiratory role as a pharyngeal dilator. PMID- 1629089 TI - Relative intensity of muscular contraction during shivering. AB - The intensity of cold-induced shivering, quantified by surface electromyography (EMG) and then expressed as a function of the maximal myoelectrical activity (integrated EMG) obtained during a maximum voluntary contraction (MVC), was examined in this study in individuals classified by body fat. In addition, the relationship between shivering and metabolic rate (MR) and the relative contribution of various muscle groups to total heat production were studied. Ten seminude male volunteers, 5 LEAN (less than 11% body fat) and 5 NORM (greater than 15% body fat) were exposed to 10 degrees C air for 2 h. EMG of six muscle groups (pectoralis major, rectus abdominis, rectus femoris, gastrocnemius, biceps brachii, and brachioradialis) was measured and compared with the EMG of each muscle's MVC. A whole body index of shivering, determined from the mass-weighted intensity of shivering of each muscle group, was correlated with MR. After the initial few minutes of exposure, only the pectoralis major, rectus femoris, and biceps brachii continued to increase their intensity of shivering. Shivering intensity was higher in the central muscles, ranging from 5 to 16% of MVC compared with that in the peripheral muscles, which ranged from 1 to 4% of MVC. Shivering intensities were similar in the peripheral muscles for the LEAN and NORM groups, whereas differences occurred in the trunk muscles for the pectoralis major and rectus abdominis. The whole body index of shivering correlated significantly with each individual's increase in MR (r = 0.63-0.97).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629090 TI - Tissue and airway impedance of excised normal, senile, and emphysematous lungs. AB - We partitioned pulmonary resistance (RL) in excised normal, senile, and emphysematous human lungs at various distending pressures; peripheral resistance (Rp) was measured by means of retrograde catheters and lung tissue resistance (Rti) by means of pleural capsules. By subtracting Rp from RL and Rti from Rp, we obtained, respectively, central (Rcaw) and peripheral (Rpaw) airway resistance. We determined also lung volumes, the elastic recoil pressure-volume curve, and the forced expiratory volume in 1 s-to-vital capacity ratio (FEV1/VC). The functional data were related to morphometry: mean linear intercept (Lm), diameter (d), and density (n/cm2) of membranous bronchioles. In the three groups of lungs, Rti demonstrates a marked negative frequency dependence and increases with transplumonary pressure. In emphysematous lungs, the increase of RL is mainly due to an increase of Rpaw; in addition, Rcaw and Rti are higher than normal. In the group of senile lungs, airway resistances are within normal range, but Rti is slightly increased. FEV1/VC is related to Rpaw and elastic recoil pressure; Rpaw is related to d and n/cm2, and Rti is related to dynamic elastance and to Lm. PMID- 1629091 TI - Ventilatory and hematopoietic responses to chronic hypoxia in two rat strains. AB - Hilltop (H) and Madison (M) strains of Sprague-Dawley rats exhibit strikingly different susceptibilities to the effects of chronic altitude exposure. The H rats develop greater polycythemia, hypoxemia, and pulmonary hypertension. We studied ventilation, pulmonary gas exchange, tissue oxygenation, and hematologic adaptations in the two rat strains during a 50-day exposure to a simulated altitude (HA) of 5,500 m (18,000 ft). There were no strain differences among the variables we studied under sea level (SL) conditions. Within the first 14 days of hypoxic exposure, the only significant strain differences were that erythropoietin (EPO) rose much higher and erythroid activity was greater in the H rats, even though arterial Po2 and PCo2 (Pao2 and PaCo2, respectively), renal venous PO2 (Prvo2), and ventilation (VE) were equivalent in the two strains during this time. By day 14 at HA, the H rats had significantly higher erythroid activity, hematocrit (Hct), and EPO levels, significantly lower PaO2 and PrvO2, but equivalent VE and PaCO2. These changes persisted for the remainder of the exposure, except that the Hct continued to rise and the increase was greater in H rats. Despite the greater O2-carrying capacity of H rats in the later stages of hypoxic exposure, PaO2 and PrvO2 were significantly lower in H rats. There were no strain differences at either SL or HA in ventilatory responses to hypercapnia or hypoxia, in blood O2 affinity or 2,3-diphosphoglycerate, in extrarenal production of EPO, or in EPO clearance. We conclude that early in the hypoxic exposure the H rats produce more EPO at apparently equivalent levels of hypoxia, and this is the first step in the pathogenesis of the maladaptation to HA manifest by H rats. We find no consistent evidence that differences in VE contribute to the variable susceptibility to hypoxia in the two rat strains. PMID- 1629092 TI - Effect of hand heating by a warm air box on O2 consumption of the contralateral arm. AB - Arterialization of venous blood is often used in studying forearm metabolism. Astrup et al. [Am. J. Physiol. 255 (Endocrinol. Metab. 18): E572-E578, 1988] showed that heating of the hand by a warming blanket caused a redistribution of blood flow in the contralateral arm and thus introduced errors in forearm skeletal muscle flux calculations. The present study was undertaken to investigate how hand heating by a warm air box (60 degrees C) would affect metabolism and blood flow in the contralateral arm before and during 3 h after a glucose load. Eleven healthy volunteers (5 males, 6 females) underwent an oral glucose tolerance test (70 g) on two different occasions, one test with and one without heating of the contralateral hand, in random order. Heating the hand for 30 min before glucose intake did not affect skin temperature, rectal temperature, deep venous oxygen saturation, forearm blood flow, or oxygen consumption of forearm skeletal muscle. Although, after the glucose load, heating significantly increased forearm blood flow (P less than 0.05), the integrated response after glucose was not significantly different between control and heating experiments [67 +/- 43 and 117 +/- 41 (SE) ml/100 ml tissue]. With both conditions, there was an increase in skin temperature (P less than 0.001, integrated response control: 369 +/- 79 and heating: 416 +/- 203 degrees C) and oxygen consumption of forearm muscle (control: 290 +/- 73, P less than 0.05 and heating: 390 +/- 130 mumol/100 ml, P less than 0.05) after glucose intake. These responses did not significantly differ between the conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629093 TI - Postinspiratory neuronal activities during behavioral control, sleep, and wakefulness. AB - Cells that discharge in early expiration and inhibit other respiratory cells purportedly cause a separate phase of the respiratory cycle that has been named "postinspiration." Our objective was to study these postinspiratory cells in the intact unanesthetized cat during sleep, wakefulness, and behavioral inhibition of inspiration, but we were unable to find cells with strong and consistent activity confined to early expiration. Instead, we found that various cell types were active in early expiration. They included inspiratory-expiratory phase-spanning cells, retrofacial augmenting expiratory cells with bursts in early expiration, retrofacial decrementing expiratory cells, tonic expiratory cells, and cells with variable activity in the early part of expiration. Just as the cell types active during early expiration were heterogeneous so too were their activities during behavioral inhibition of inspiration and during sleep. These results suggest that the state of early expiration is determined by many different cell types rather than a single class of postinspiratory cells. PMID- 1629094 TI - Spatial correlation of regional pulmonary perfusion. AB - Despite the heterogeneous distribution of pulmonary blood flow, perfusion appears to be spatially ordered, with neighboring regions of lung having similar magnitudes of flow. This premise was tested by determining the spatial correlation of regional flow [rho(d)] as a function of distance (d) between regions. Regional pulmonary perfusion was measured in both supine and prone positions in seven anesthetized mechanically ventilated dogs with radiolabeled microspheres. After excision and drying, the lungs were cubed into pieces 1.2 cm on a side, with a three-dimensional coordinate assigned to each piece. The microsphere-determined flow to each piece was measured by radioactive counts, and rho(d) was calculated for all paired pieces within the same lobe. rho(d) was greatest for adjacent pieces (d = 1.2 cm) and decreased with increasing d, becoming negative at large distances in all dogs and positions. The spatial correlation of flow between adjacent pieces, rho(1.2 cm), was greater in the supine than in the prone position (0.66 vs. 0.72, P less than 0.05). The observations for each dog and position were fit to the equation rho(d) = d(a)+b.d+c, and the coefficients were used to compare rho(d) in the supine and prone positions. rho(d) differed in the two positions (P less than 0.05), with rho(d) falling off more rapidly with distance in the supine position. When trends in flow due to gravity were mathematically removed, differences between supine and prone positions were no longer observed. The spatial correlation of regional pulmonary perfusion was anisotropic in both supine and prone positions. The observation that regional pulmonary perfusion is highly correlated over large spatial distances has important implications for models of flow distribution. PMID- 1629095 TI - Effects of endothelin-1 and conversion of big endothelin-1 in the isolated perfused rabbit lung. AB - We examined the effects of endothelin-1 (ET-1) on pulmonary hemodynamic and transvascular fluid filtration and the conversion of big endothelin-1 (big ET-1), a precursor of ET-1, in isolated perfused rabbit lungs at constant vascular and airway pressures. Furthermore we examined whether ET-1 contributes to cyclooxygenase metabolism. The perfusate flow decreased significantly after bolus administration of 1 or 0.1 nmol of ET-1. Lung weight did not increase throughout the experimental period. Big ET-1- (1 nmol) induced decrease in the flow was slow in developing, although the maximum response was comparable to that induced by the same dose of ET-1. The concentration of bit ET-1 in the perfusate progressively decreased, while that of ET-1 increased in a time-dependent manner. Phosphoramidon, an inhibitor of metalloproteinase, suppressed the pressor effect of big ET-1 (P less than 0.01) and the increase in the concentration of ET-1 in the perfusate (P less than 0.05). The present findings provide the first evidence suggesting that the potent vasocontractile effect of big ET-1 in pulmonary circulation can be attributed to the production of ET-1 by the conversion from big ET-1 in the vascular bed. ET-1-induced perfusate flow changes were not affected by indomethacin, and the concentration of 6-ketoprostaglandin F1 alpha, a metabolite of prostacyclin, did not increase after ET-1 administration. PMID- 1629096 TI - Role of endothelium-derived relaxing factor in active hyperemia of the canine diaphragm. AB - To assess the effect of endothelium-derived relaxing factor (EDRF) on diaphragmatic vascular resistance at rest and during contractions, we studied an in situ isolated diaphragm preparation in anesthetized and mechanically ventilated dogs. The arterial supply of the left diaphragm (phrenic artery) was catheterized and perfused with arterial blood at a fixed flow rate. Drugs were infused through a side port of the arterial catheter at 1/100th of the phrenic arterial flow. The inferior phrenic vein was catheterized to complete the isolation from the systemic circulation. Three sets of experiments were performed. In set 1 (n = 3), we infused endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside, SNP) dilators at increasing concentrations. ACh and SNP infusion elicited a dose-dependent decline in phrenic vascular resistance (Rphr) at concentrations greater than 10(-8) M and 0.50 micrograms/ml, respectively. In set 2 (n = 15), we infused an inhibitor of EDRF synthesis and release, L-argininosuccinic acid (ArgSA), at increasing concentrations (10(-4), 3 x 10(-4), and 6 x 10(-4) M). ArgSA produced a dose dependent increase in Rphr. Infusion of another EDRF inhibitor (NG-nitro-L arginine, LNA, 6 x 10(-4) M) elicited increase in Rphr similar to that induced by ArgSA. In set 3 (n = 25), we infused ArgSA or LNA (6 x 10(-4) M) simultaneously with ACh and SNP and during sustained (2-Hz) contractions of the diaphragm. Both ArgSA and LNA completely reversed ACh vasodilation, whereas SNP vasodilation was reversed by 26 and 11%, respectively. ArgSA or LNA infusion during contractions reversed vasodilation by 48 and 52%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629097 TI - Physical models of the smaller pulmonary airways. AB - Any internalized flow exhibits closely coupled interactions with its confining geometry. Efforts to gain an understanding of in vivo airway transport phenomena, therefore, dictate that careful attention to be paid to those anatomic airway features that constrain and modify regional air movement. We present a series of analyses of human small airway casts to refine and extend the current geometric description of small airway bifurcations. Airway shape factors believed to have a high propensity to alter the fluid dynamics of airflows within this region are specifically addressed. The results of these anatomic and fluidic analyses are used to develop two average symmetrical and asymmetrical bifurcation patterns. Finally, methods for the production of physical bifurcation models conforming to these requirements are presented to develop a rational representation of anatomic as well as flow similitude during airway research. PMID- 1629098 TI - Effects of lung inflation and blood flow on capillary transit time in isolated rabbit lungs. AB - In a previous study, direct measurements of pulmonary capillary transit time by fluorescence video microscopy in anesthetized rabbits showed that chest inflation increased capillary transit time and decreased cardiac output. In isolated perfused rabbit lungs we measured the effect of lung volume, left atrial pressure (Pla), and blood flow on capillary transit time. At constant blood flow and constant transpulmonary pressure, a bolus of fluorescent dye was injected into the pulmonary artery and the passage of the dye through the subpleural microcirculation was recorded via the video microscope on videotape. During playback of the video signals, the light emitted from an arteriole and adjacent venule was measured using a video photoanalyzer. Capillary transit time was the difference between the mean time values of the arteriolar and venular dye dilution curves. We measured capillary transit time in three groups of lungs. In group 1, with airway pressure (Paw) at 5 cmH2O, transit time was measured at blood flow of approximately 80, approximately 40, and approximately 20 ml.min 1.kg-1. At each blood flow level, Pla was varied from 0 (Pla less than Paw, zone 2) to 11 cmH2O (Pla greater than Paw, zone 3). In group 2, at constant Paw of 15 cmH2O, Pla was varied from 0 (zone 2) to 22 cmH2O (zone 3) at the same three blood flow levels. In group 3, at each of the three blood flow levels, Paw was varied from 5 to 15 cmH2O while Pla was maintained at 0 cmH2O (zone 2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629099 TI - Effects of moderate hypothermia on O2 consumption at various O2 deliveries in a sheep model. AB - The effects of modest hypothermia on oxygen consumption (VO2) were studied at various levels of oxygen delivery (DO2) in six sheep. Each animal was placed on cardiopulmonary bypass by extrathoracic cannulations. DO2 was varied by changing blood flow through an extracorporeal circuit. VO2 was measured spirometrically across a membrane lung. VO2 was initially measured at various levels of DO2 at normothermic temperatures (39 degrees C). The animals were then cooled to 33 degrees C. DO2 was varied, and the corresponding VO2's were determined. The data at both temperatures demonstrated the biphasic relationship of VO2 to various levels of DO2. A critical level of DO2 (DO2 crit) was defined to reflect the transition area between the dependent and independent portions of the consumption delivery curve. The average baseline VO2's on the delivery independent portion of the curve were calculated to be 5.33 and 3.17 ml O2.kg-1.min-1 at 39 and 33 degrees C, respectively (P less than 0.001). The corresponding DO2 crit's were 6.17 and 4.57 ml O2.kg-1.min-1 (P less than 0.05). The oxygen extraction ratios at DO2 crit for each of these temperatures did not differ significantly. We conclude that hypothermia, by lowering baseline VO2, reduces DO2 crit. Hypothermia may therefore reduce or eliminate the anaerobic metabolism and subsequent acidosis that would otherwise occur during normothermia at low levels of DO2. PMID- 1629100 TI - Muscle accounts for glucose disposal but not blood lactate appearance during exercise after acclimatization to 4,300 m. AB - We hypothesized that the increased blood glucose disappearance (Rd) observed during exercise and after acclimatization to high altitude (4,300 m) could be attributed to net glucose uptake (G) by the legs and that the increased arterial lactate concentration and rate of appearance (Ra) on arrival at altitude and subsequent decrease with acclimatization were caused by changes in net muscle lactate release (L). To evaluate these hypotheses, seven healthy males [23 +/- 2 (SE) yr, 72.2 +/- 1.6 kg], on a controlled diet were studied in the postabsorptive condition at sea level, on acute exposure to 4,300 m, and after 3 wk of acclimatization to 4,300 m. Subjects received a primed-continuous infusion of [6,6-D2]glucose (Brooks et al., J. Appl. Physiol. 70: 919-927, 1991) and [3 13C]lactate (Brooks et al., J. Appl. Physiol. 71:333-341, 1991) and rested for a minimum of 90 min, followed immediately by 45 min of exercise at 101 +/- 3 W, which elicited 51.1 +/- 1% of the sea level peak O2 uptake (65 +/- 2% of both acute altitude and acclimatization peak O2 uptake). Glucose and lactate arteriovenous differences across the legs and arms and leg blood flow were measured. Leg G increased during exercise compared with rest, at altitude compared with sea level, and after acclimatization. Leg G accounted for 27-36% of Rd at rest and essentially all glucose Rd during exercise. A shunting of the blood glucose flux to active muscle during exercise at altitude is indicated. With acute altitude exposure, at 5 min of exercise L was elevated compared with sea level or after acclimatization, but from 15 to 45 min of exercise the pattern and magnitude of L from the legs varied and followed neither the pattern nor the magnitude of responses in arterial lactate concentration or Ra. Leg L accounted for 6-65% of lactate Ra at rest and 17-63% during exercise, but the percent Ra from L was not affected by altitude. Tracer-measured lactate extraction by legs accounted for 10-25% of lactate Rd at rest and 31-83% during exercise. Arms released lactate under all conditions except during exercise with acute exposure to high altitude, when the arms consumed lactate. Both active and inactive muscle beds demonstrated simultaneous lactate extraction and release. We conclude that active skeletal muscle is the predominant site of glucose disposal during exercise and at high altitude but not the sole source of blood lactate during exercise at sea level or high altitude. PMID- 1629101 TI - Individuality of breathing patterns during hypoxia and exercise. AB - Breathing was recorded via a pulsed ultrasonic flowmeter in 11 healthy subjects, at rest and during steady-state exercise (at 50% of their maximal O2 consumption) at both sea level (200 m) and simulated altitude (4,500 m in a hypobaric chamber). The pattern of breathing was quantified breath by breath in terms of classical respiratory variables (tidal volume and inspiratory and expiratory times), and the shape of the entire airflow profile was quantified by harmonic analysis. Statistical tests were used to compare the within-individual with the between-individual variations. In comparing the sea level vs. altitude rest (16% increase in ventilation) and sea level vs. altitude exercise (40% increase in ventilation) airflow profiles, we found a significantly greater resemblance within the individual than between individuals. Comparisons of sea level rest and exercise (295% increase in ventilation) and altitude rest and exercise (375% increase in ventilation) revealed no similarity within individuals. Despite airflow profile changes between rest and exercise, it is still possible to attest to a diversity of flow profile between individuals during exercise. Hypoxia at rest or during exercise does not alter the phenomenon of the individuality of breathing patterns. PMID- 1629102 TI - Measurement of interrupter resistance in rabbits exposed to methacholine aerosols. AB - We studied the effect of increasing airway resistance on equilibration of airway and alveolar pressure during passive expiratory airflow interruption. In 10 anesthetized and paralyzed rabbits, airway and alveolar pressures were compared before and after airway resistance was increased with methacholine. In all studies, airway pressure rose to equilibrate with alveolar pressure immediately after the interruption (delta Pinit) regardless of increases in airway resistance. The pressures then remained equal during the interruption while gradually increasing to plateau (delta Pdiff). Before methacholine exposure, delta Pdiff was small (0.6 +/- 0.3 cmH2O). Steady-state resistance calculated from the sum of delta Pinit and delta Pdiff was similar to airway resistance calculated from delta Pinit alone. After methacholine, increased airway resistance was accompanied by increased delta Pdiff (2.0 +/- 0.5 cmH2O), causing disproportionate increase in steady-state resistance. delta Pdiff increases were equal in the airway and alveoli, implying resistive changes distal to the sampled alveoli. Thus increasing airway resistance did not delay pressure equilibration across airways. However, increases in airway resistance were accompanied by tissue resistive changes that were greater than the increases in airway resistance. PMID- 1629103 TI - Effect of vagal stimulation and parenteral acetylcholine on canine trachealis muscle shortening. AB - Canine trachealis smooth muscle shortening (TMS) in response to vagal nerve stimulation is approximately 30%, far less than the 70% predicted from in vitro studies. We hypothesized that in vivo airway smooth muscle activation during vagal stimulation may be submaximal, and in this study we wished to determine TMS during maximal activation. TMS was studied in 12 alpha-chloralose-anesthetized dogs during vagal stimulation, systemic acetylcholine injection, and local acetylcholine injection. Bilateral vagal stimulation produced TMS of 26 +/- 5% (SE) length at functional residual capacity (LFRC). Maximal TMS during systemic injection of acetylcholine was 28 +/- 12% LFRC but may have been limited by delivery of acetylcholine to the muscle because asystole occurred at higher concentrations. TMS was greatest during local injection of acetylcholine (48 +/- 7% LFRC). There was a greater increase in pulmonary resistance and decrease in dynamic compliance during systemic acetylcholine injection than during vagal stimulation. We conclude that bilateral vagal nerve stimulation does not maximally activate trachealis smooth muscle but that the maximal shortening achieved with local injection of acetylcholine is still less than isotonic shortening in vitro. These data suggest that maximal shortening in vivo is limited by the afterload provided by the tracheal cartilaginous rings. PMID- 1629104 TI - Evaluation of prostaglandin F2 alpha and prostacyclin interactions in the isolated perfused rat lung. AB - To characterize the interactions between prostaglandin F2 alpha and prostacyclin in controlling tone in the pulmonary circulation, isolated rat lungs were ventilated, perfused with blood, and subjected to challenge by prostaglandin F2 alpha in increasing doses. The pulmonary resistance was evaluated using occlusion techniques that separate the resistance into segments of large and small arteries and veins. The total vascular compliance was evaluated using outflow occlusion. Resistance increased after prostaglandin F2 alpha, and this resistance change was primarily in the small artery segment. The maximum resistance increase by prostaglandin F2 alpha (Rmax,PGF2 alpha), calculated from the Michaelis-Menton equation, was 16.6 +/- 3.6 cmH2O.l-1.min.100 g-1 for total vascular resistance with a concentration required to produce 50% Rmax (K0.5) of 5.26 +/- 3.57 nM. The Rmax,PGF2 alpha for small artery resistance was 13.5 +/- 2.4 cmH2O.l-1.min.100 g 1 with a K0.5 of 2.35 +/- 1.57 nM. The vascular compliance decreased during vasoconstriction by prostaglandin F2 alpha, and the maximum decrease in compliance (Cmin,PGF2 alpha) was -0.43 +/- 0.12 ml/cmH2O with a K0.5 of 2.84 +/- 2.99 nM. At each dose of prostaglandin F2 alpha, prostacyclin was administered in increasing doses to reverse the vasoconstriction caused by prostaglandin F2 alpha. For each concentration of prostaglandin F2 alpha, prostacyclin almost completely reversed the resistance increases and approximately one-half the compliance decrease. The maximum change in vascular resistance or compliance produced by prostacyclin was dependent on the dose of prostaglandin F2 alpha; yet the K0.5 for prostacyclin was within the picomolar range for all doses of prostaglandin F2 alpha.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629105 TI - Comparison of arousal responses to tracheal and face mask occlusions in sleeping newborn piglets. AB - The arousal responses after occlusion of the airway at the mid-trachea were compared with the responses after occlusion of the airway in a face mask in chronically instrumented 3- to 5-day-old piglets. For each site of occlusion arousal latency was significantly longer from active sleep than from quiet sleep. There was a significant increase in the frequency of early arousals after face mask occlusions compared with tracheal occlusions in both sleep states. During quiet sleep the frequency of arousal by 1 s after occlusion was 0.55 with face mask occlusions compared with 0.28 with tracheal occlusion (P less than 0.01). During active sleep the frequency of arousal by 3 s after a face mask occlusion was 0.32 compared with 0.08 after tracheal occlusion (P less than 0.05). Arousal from quiet sleep occurred before changes in arterial oxygen saturation. During active sleep mean saturation at arousal was not different between face mask and tracheal occlusions. Exposure of the upper airway to the pressures generated during airway occlusions results in earlier arousal in both quiet and active sleep, indicating a potential role for upper airway mechanoreceptors in initiating arousal in the newborn piglet. PMID- 1629106 TI - Regulation of glucose turnover at the onset of exercise in the dog. AB - The early responses of endogenous glucose production (Ra), glucose utilization (Rd), and glucoregulatory hormones to moderate treadmill exercise (12% incline, 100 m/min, 60 min) were examined in dogs. Rd increased rapidly and progressively from the start of exercise. The change in Ra, as estimated with a variable-volume model of glucose kinetics, was biphasic, with an abrupt increase by 8.5 +/- 2.3 mumol.min-1.kg-1, followed by a delayed further increase that matched Rd 11-22 min after the onset of exercise. The plasma glucagon-to-insulin molar ratio fell slightly at the onset of exercise and then increased gradually. The glucagon-to insulin ratio was correlated with Ra over the entire exercise period (r = 0.63, P less than 0.0001), but not during the early part of exercise, when Ra increased rapidly. The catecholamine- (epinephrine plus norepinephrine) to-insulin molar ratio was correlated with Ra during the early period (r = 0.52, P less than 0.01) and over the entire period of exercise (r = 0.66, P less than 0.0001). Our results confirm previous demonstrations that the glucagon-to-insulin molar ratio is an important regulator of Ra during exercise. We hypothesize that the catecholamine-to-insulin molar ratio is important during the early period of exercise and possibly during late exercise as an additional regulatory factor to the glucagon-to-insulin molar ratio. PMID- 1629108 TI - Estimation of glucose production during exercise with a one-compartment variable volume model. AB - A variable-volume one-compartment model of glucose kinetics and step increases in the rate of tracer infusion were examined for estimation of endogenous glucose production (Ra) during moderate exercise in dogs. A primed infusion of D-[3 3H]glucose was left constant or increased 1.5-, 2-, 3-, 4-, or 5-fold at the onset of a 60-min period of exercise. Application of a regression method, in which Ra and the effective distribution volume were estimated over time, revealed dynamic changes in Ra that were not evident during the constant tracer infusion with a fixed-volume model. Application of the fixed-volume model to studies performed with a two- or three-fold step increase in tracer resulted in the lowest sum-of-squares difference from the regression method. Our results demonstrate that application of a variable-volume model can be achieved during exercise by enrichment of the plasma specific activity through step increases in the rate of tracer infusion and application of a regression method. Alternately, estimates of Ra with a fixed-volume model can be improved by enrichment of the plasma specific activity through a single step increase in the rate of tracer infusion. Our results suggest that when endogenous Ra is changing rapidly, such as at the onset of exercise, these methods will provide a more accurate estimate of Ra than the standard fixed-volume model and constant tracer infusion. PMID- 1629109 TI - Radiological case of the month. Tardus parvus abnormality in renal artery stenosis. PMID- 1629107 TI - Effects of nonideal input functions on PET measurements of pulmonary blood flow. AB - Regional pulmonary blood flow (rPBF) can be measured with an intravenous infusion of 15O-labeled water and positron emission tomography (PET). The current method depends on two assumptions related to the input of activity to the lung during the scan: 1) the pulmonary arterial tracer input is constant (i.e., a "step function" in shape), and 2) the scan begins at the instant of arrival of the step function. To determine the effect that departures from these assumptions might have on the measurement of rPBF, we performed a series of mathematical simulations for three different input functions: 1) a step function that arrived either 1 or 2 s before or after scan start; 2) a dispersed input function, with activity rising during the scan period; and 3) a combination of these two errors. Calculated values, based on the standard assumptions, were compared against the "known" values used in generating the simulated data. The results show that timing errors associated with starting the scan late cause an overestimation of rPBF, whereas timing errors due to low regional flow or departures from the assumed step input function both cause an underestimation of true rPBF. Thus, in actual practice, the combined errors probably partially offset one another. Except for states of truly high rPBF and low lung density, the errors remain less than 15% of the true value. We conclude that PET measurements of rPBF are not highly sensitive to these presumably common departures from the assumed pulmonary arterial input function to lung regions of interest. PMID- 1629110 TI - Doctor traps. PMID- 1629111 TI - Age as a prognostic factor in cancer of the cervix: the UAMS experience. AB - Current literature has conflicting reports as to the effect of age on prognosis in cancer of the uterine cervix. In order to evaluate this in our patient population we undertook a retrospective chart review of 235 cases of cervical cancer that were seen at the Central Arkansas Radiation Therapy Institute (CARTI) and the University of Arkansas for Medical Sciences (UAMS) from March 1974 to June 1985 and were followed for a minimum of 54 months. State, grade and age greater than 70 years were significant predictors. Factors that were not statistically significant were race and morphology. Age less than 40, approached statistical significance as a predictive value. Our patients younger than age 40 had a tendency toward a slightly decreased survival when compared to those ages 40-60 and also a much decreased disease-free interval (50 months versus 97 months). This paper was presented on October 25, 1990 at Student Research Day at UAMS. PMID- 1629112 TI - Tobacco--masters of misinformation. PMID- 1629113 TI - Arkansas pharmacists to begin patient counseling. PMID- 1629114 TI - Problem-based curriculum and its value to Indian medical schools: description of the curriculum. AB - The decade of the 80's has seen the implementation of the problem-based curriculum (PC) (also called "parallel" or "student-centred" curriculum) in several medical schools in the United States. This new educational technique emphasizes active student participation and a hands-on learning process supplemented by judicious intervention by the faculty teachers. The students (often volunteers) are usually selected for their motivation rather than for highest intelligence or class ranking. For a period of two years, they meet twice or thrice-weekly in group sessions to explore problem cases developed by faculty for that special purpose. We describe the parallel curriculum here in some detail and suggest that medical educators in India give serious consideration to implementation of such a curriculum or its modification in their institutions. Medical graduates will benefit from the hands-on emphasis of this curriculum as well as the development of a disciplined approach in the handling of clinical problems. PC diminishes the stress levels associated with the traditional curriculum and lets the students play an active role in their education. PC will make them better prepared to face challenges during their clinical years and subsequent careers and should offset some of the weaknesses in the current educational system. PMID- 1629115 TI - Thrombotic thrombocytopenic purpura. PMID- 1629116 TI - Refractory hypotension. A clue to myxedema coma. PMID- 1629117 TI - Normal maximal expiratory and inspiratory pressures in healthy teenagers. AB - Maximal expiratory pressure at total lung capacity and maximal inspiratory pressure at residual volume were measured in 364 male and 325 female healthy teenage subjects. Predictive equations have been drawn based on coefficients of age, height and weight. The pressures may be used to evaluate respiratory muscle strength and follow the progress in patients with neuromuscular disorders, dyspnoea and respiratory failure. PMID- 1629118 TI - Trace elements. PMID- 1629119 TI - Carcinoma in an oesophageal diverticulum. AB - A young male who had minimal dysphagia since childhood complained of increasing difficulty in swallowing for a few months. Upper Gastrointestinal endoscopy was normal on two occasions done by two gastroenterologists. Barium swallow showed minimal extrinsic pressure on the oesophageal wall. X-ray chest was normal. CT scan showed a large growth close to the oesophagus. Resection of the growth showed a carcinoma completely filling an oesophageal diverticulum with a normal oesophageal lumen. PMID- 1629120 TI - Spinal epidural abscess in E coli septicaemia. PMID- 1629121 TI - Saddle embolism of aorta. AB - Aortic saddle embolus is a rare but serious form of arterial embolisation in patients with myocardial infarction. Four patients with aortic saddle embolism with peripheral propagation of the clott are reported. Two patients had suffered an attack of acute anterior myocardial infarction (one and four weeks respectively) prior to the embolic episode. One patient had a transmural myocardial infarct five years ago, and the 4th patient had dilated cardiomyopathy. The onset was sudden, marked by pain, parasthesias, pallor, pulselessness in three patients, and gradual in one. Two of the three patients (both females) in whom clott migration occured in only one limb developed below knee gangrene of the affected side. In one patient (a young male) clott migration occurred in both popliteal arteries and the limbs were spared from developing gangrene although he continues to have leg angina. One patient presented with intermittent calf claudication only. All our patients reported late due to which none could be subjected to embolectomy. PMID- 1629122 TI - Antiphospholipid antibody syndrome of systemic lupus erythematosus presenting as deep vein thrombosis. AB - We are reporting a young lady with protracted deep vein thrombosis of her left leg which turned out to be antiphospholipid (anticardiolipin) antibody syndrome of ANA positive systemic lupus erythematosus. Lupus anticoagulant was demonstrated by prolongation of activated partial thromboplastin time and Russell's viper venom time. She had no anti-thrombin III deficiency. PMID- 1629123 TI - Carotid sinus syndrome associated with carcinoma of the pyriform fossa. AB - A patient who developed syncope due to carotid sinus syndrome is described. The patient was suffering from carcinoma of the pyriform fossa for the past one year and received radiotherapy in the region of the neck for the same. Demand pacing was ineffective in alleviating syncopal episodes. The patient responded to oral administration of an anticholinergic (belladonna) and a sympathomimectic agent (orciprenaline). PMID- 1629124 TI - Spontaneous passage of nasogastric tube through the gut. PMID- 1629125 TI - Efficacy and safety studies on ayurvedic drugs. PMID- 1629126 TI - Prognosis and therapy in chronic myeloid leukaemia. PMID- 1629127 TI - Falciparum malaria and jaundice. PMID- 1629128 TI - Eosinophilic polymyositis without peripheral eosinophilia. PMID- 1629129 TI - Haemorrhagic meningitis due to Bacillus anthrax. PMID- 1629130 TI - Tubercular colitis in a patient with systemic lupus erythematosus: diagnosis by stool examination. PMID- 1629131 TI - Hypoglycemia presenting as hemiparesis in a diabetic patient. PMID- 1629132 TI - Renal dysfunction in enteric fever. PMID- 1629133 TI - Epilepsy as a manifestation of neurocysticercosis. PMID- 1629135 TI - Confusing insulin syringes. PMID- 1629134 TI - Atrial flutter in myocardial infarction. PMID- 1629136 TI - IgM ELISA follow-up of spiramycin treatment for toxoplasmosis: should the drug be prescribed in India? PMID- 1629137 TI - Carrier detection in muscular dystrophy. PMID- 1629138 TI - Hypertension monotherapy with ACE inhibitors. PMID- 1629139 TI - Amoebic liver abscess--an unusual presentation report of a case. PMID- 1629140 TI - Short PR interval and abnormal systolic time interval as a method of carrier detection in maternal relations of patients with muscular dystrophy. AB - Seventeen relatives of patients with Duchenne's muscular dystrophy (Group A) and 6 relatives of patients with adult type of muscular dystrophy (Group B) were studied. Short PR interval on electrocardiogram and abnormal systolic time interval (STI) were consistent findings in 14 of 15 female relatives (93.35%) in group A, while these criteria were lacking in group B. Myopathic pattern (i.e. tachycardia, short PR interval, R/S ratio in V1 greater than 1.5, significant Q wave in V4, V5, V6 on electrocardiogram) was present in two (13.35%) of 15 female relatives from group A. It was absent in group B. Male relatives in both the groups had normal electrocardiogram and normal systolic time interval. PMID- 1629141 TI - Tuberculosis and leprosy--not uncommon association. PMID- 1629142 TI - Enalapril monotherapy in essential hypertension. AB - Thirty adults with essential hypertension (systolic BP greater than 150 mmHg or diastolic BP greater than 100 mmHg) were treated with 5-20 mg of enalapril to study its anti-hypertensive efficacy and safety. Ten patients had mild hypertension (diastolic BP greater than 90 mmHg and less than 105 mmHg), 10 had moderate hypertension (diastolic BP greater than 105 mmHg and less than 115 mmHg) and 6 had severe hypertension (diastolic BP greater than 115 mmHg). Of the 20 patients who completed the trial, 9 (45%) showed optimum reduction of BP to less than 130/90 mmHg) and a further 7 (35%) showed significant reduction. The mean fall in systolic BP was 32.5 mmHg (0-80 mmHg) and in diastolic BP was 18.5 mmHg (0-50 mmHg). The peak fall in BP was achieved in 3.5 weeks (1-6 weeks) with a mean dose of 7.2 mg of enalapril daily (5-15 mg/day). Mild side effects not needing drug withdrawal were seen in 8/20 patients (40%). Monotherapy with enalapril appears to be effective and safe as step one therapy for patients with essential hypertension. PMID- 1629143 TI - Endosulfan poisoning: a study of 22 cases. AB - Twenty two cases of endosulfan poisoning with their symptomatology are reported. The management and lack of awareness regarding specific treatment are highlighted. PMID- 1629144 TI - Percutaneous transluminal coronary angioplasty in distal lesions. AB - Of 210 patients in whom percutaneous transluminal coronary angioplasties [PTCA] were performed during the period of 2 years (June 1987 to August 1989), 55 had distal lesions. These included 50 males and 5 females with the lesions in left anterior descending [LAD] artery after the origin of the second diagonal branch, circumflex [Cx] artery after the origin of the obtuse marginal [OM], and right coronary artery [RCA] after the acute marginal branch. There were a total of 71 distal lesions, involving the LAD [51%], Cx [20%], and RCA [29%]. The overall success rate with PTCA was 91%. There were 4 acute closures of vessels; all were redilated with balloon angioplasty. One of these was sent for emergency bypass surgery after balloon dilatation. There was no death. With improvement in balloon catheters and guidewires, the feasibility and success of PTCA in distal lesions have increased remarkably, thus expanding the horizon of PTCA. PMID- 1629145 TI - Mitral annular calcification in untreated chronic renal failure. AB - Clinical, biochemical, radiological and echo-cardiographic (echo) evaluation was done prospectively in 50 patients of untreated end stage chronic renal failure (CRF). While clinically congestive cardiac failure (CCF) was diagnosed in 24%, low ejection fraction on echo was found in only 16%. Echo in these cases showed evidence of cardiac chamber dilatation in most (mean LVID (D) 54.1 +/- 6.51 and (S) 36.4 +/- 6.9 mm, but parameters of cardiac functions were normal in most. Mitral annular calcification (MAC) was detected on echo in 26%. On comparing patients with MAC (Group I) and those without MAC (Group II), the aetiological factor found more frequently in Group I was diabetes (61.5% vs 35.1%, P less than 0.05). Clinical features such as older age (mean age 54 years vs 45.5 years), severe hypertension, and grade IV and above murmur (15.2% vs none) were more common among group I patients. However, the difference was not statistically significant. Parameters of calcium metabolism were similar in the two groups. Conduction disturbances (30.7% vs 5.4%) were significantly more common in Group I (P = 0.05). The mitral regurgitation due to MAC was of no haemodynamic significance. Complications of MAC syndrome were rare. PMID- 1629146 TI - Gene therapy: a status report. AB - Gene therapy is a way to treat disease by transfer of genetic material into the cells of a diseased organism. Generally it is transferred in the form of one or few genes. There is a tremendous potential for application of this technique to the treatment of human hereditary diseases, particularly single gene disorders. Due to ethical and practical reasons, it is currently being used only as somatic cell therapy but it could be achieved by germline also. The major problem in gene therapy is achieving an efficient gene transfer and a persistent gene expression in appropriate somatic cells. PMID- 1629147 TI - Philadelphia chromosome. PMID- 1629148 TI - A squid that glows in the night: development of an animal-bacterial mutualism. PMID- 1629149 TI - Multiple transcripts encoded by the ilvGMEDA gene cluster of Escherichia coli K 12. AB - We report here that, using Northern (RNA) blots, we identified two relatively stable transcripts of 4.6 and 1.1 kb that correspond to the products of the ilvEDA and ilvE genes and two relatively unstable transcripts of 6.7 and 3.6 kb that correspond to the products of the ilvGMEDA and ilvDA genes. The transcripts were identified by the use of eight probes derived from segments of the ilvGMEDA cluster. In addition, we used two strains with deletions of ilvG or ilvDA and observed the expected decrease in transcript size in Northern blots. Primer extension with reverse transcriptase generated a 169-nucleotide product corresponding to a 5' end within the ilvED intercistronic region, 37 nucleotides from the AUG codon of the ilvD gene. This primer extension product presumably indicates the 5' end of the ilvDA transcript that we detected in Northern blots. The stability of the transcripts was monitored, and RNase E was found to play a major role in ilv transcript degradation. Transcript levels varied in response to growth in the presence of the end product amino acids and in response to the presence of the polar frameshift site in ilvG. Although there have been speculations about the identities and numbers of transcripts derived from the ilvGMEDA cluster on the basis of the identification of some of the sites of transcription initiation and termination, this is the first report of the use of Northern blots to determine the actual sizes and distribution of mRNAs present in vivo. PMID- 1629150 TI - Characterization of a Bacillus subtilis sporulation operon that includes genes for an RNA polymerase sigma factor and for a putative DD-carboxypeptidase. AB - At early stages of sporulation, the spoIIA locus is transcribed as a tricistronic (1.7-kb) operon, coding for sigma F and for two proteins that modulate the activity of sigma F. The locus is transcribed as a longer (2.9-kb) transcript at the late stages of sporulation. We show here that the longer transcript contains an additional open reading frame whose product has extensive sequence homology with DD-carboxypeptidases; the corresponding gene is designated dacF. Cotranscription of a morphogene, such as dacF, with the gene for a sigma factor suggests a way to couple transcription regulation with morphogenesis. The predicted N-terminal sequence of the DacF protein and the inhibition of sporulation by a translational dacF-lacZ fusion both suggest that the protein has a signal peptide for transport into or across a membrane. Expression of a dacF lacZ transcriptional fusion was in the forespore. The 5' end of the 2.9-kb transcript was determined by primer extension analysis. The region 5' to the end showed no homology to promoters recognized by known sigma factors but was homologous to the corresponding region of the forespore-specific 0.3-kb gene of Bacillus subtilis. PMID- 1629151 TI - Mechanism of Na(+)-dependent citrate transport in Klebsiella pneumoniae. AB - Citrate transport via CitS of Klebsiella pneumoniae has been shown to depend on the presence of Na+. This transport system has been expressed in Escherichia coli, and uptake of citrate in E. coli membrane vesicles via this uptake system was found to be an electrogenic process, although the pH gradient is the main driving force for citrate uptake (M. E. van der Rest, R. M. Siewe, T. Abee, E. Schwartz, D. Oesterhelt, and W. N. Konings, J. Biol. Chem. 267:8971-8976, 1992). Analysis of the affinity constants for the different citrate species at different pH values of the medium indicates that H-citrate2- is the transported species. Since the electrical potential across the membrane is a driving force for citrate transport, this indicates that transport occurs in symport with at least three monovalent cations. Citrate efflux is stimulated by Na+ concentrations of up to 5 mM but inhibited by higher Na+ concentrations. Citrate exchange, however, is stimulated by all Na+ concentrations, indicating sequential events in which Na+ binds before citrate for translocation followed by a release of Na+ after release of citrate. CitS has, at pH 6.0 and in the presence of 5 mM citrate on both sides of the membrane, an apparent affinity (K(app)) for Na+ of 200 microM. The Na+/citrate stoichiometry was found to be 1. It is postulated that H-citrate2- is transported via CitS in symport with one Na+ and at least two H+ ions. PMID- 1629152 TI - Secretion of CyaA-PrtB and HlyA-PrtB fusion proteins in Escherichia coli: involvement of the glycine-rich repeat domain of Erwinia chrysanthemi protease B. AB - Protease B from Erwinia chrysanthemi was shown previously to have a C-terminal secretion signal located downstream of a domain that contains six glycine-rich repeats. This domain is conserved in all known bacterial proteins secreted by the signal peptide-independent pathway. The role of these repeats in the secretion process is controversial. We compared the secretion processes of various heterologous polypeptides fused either directly to the signal or separated from it by the glycine-rich domain. Although the repeats are not involved in the secretion of small truncated protease B carboxy-terminal peptides, they are required for the secretion of higher-molecular-weight fusion proteins. Secretion efficiency was also dependent on the size of the passenger polypeptide. PMID- 1629153 TI - Localization of upstream sequence elements required for nitrate and anaerobic induction of fdn (formate dehydrogenase-N) operon expression in Escherichia coli K-12. AB - Two transcriptional activators, the FNR and NARL proteins, are required for induction of the fdnGHI operon, encoding Escherichia coli formate dehydrogenase N. The FNR protein is required for anaerobic expression, while the NARL protein mediates nitrate induction. We used primer extension to locate the transcription initiation site 29 nucleotides upstream of the fdnG translation initiation codon. Expression assays with single-copy phi (fdnG-lacZ) gene fusions containing various deletions in the fdn 5'-regulatory region delimited three distinct cis acting elements. One site, which is located at approximately -110, was required for nitrate induction. Two other sites share sequence similarity with the FNR protein binding site core consensus. The first site, centered at -42.5, was required for anaerobic induction. We used site-specific mutagenesis to change this putative FNR protein binding site into the CRP protein binding site core consensus. This change caused the fdn operon to be expressed aerobically, subject to CRP protein control. On the other hand, converting this putative FNR protein binding site into the FNR protein binding site core consensus resulted in elevated anaerobic induction of the fdn operon and also caused weak aerobic expression. The other putative FNR protein binding site, centered at -97.5, was not involved in anaerobic induction. It might play a negative role in fdn operon expression during anaerobic growth in the absence of nitrate. PMID- 1629154 TI - An efficient screen for peroxisome-deficient mutants of Pichia pastoris. AB - We describe a rapid and efficient screen for peroxisome-deficient (per) mutants in the yeast Pichia pastoris. The screen relies on the unusual ability of P. pastoris to grow on two carbon sources, methanol and oleic acid, both of which absolutely require peroxisomes to be metabolized. A collection of 280 methanol utilization-defective (Mut-) P. pastoris mutants was isolated, organized into 46 complementation groups, and tested for those that were also oleate-utilization defective (Out-) but still capable of growth on ethanol and glucose. Mutants in 10 groups met this phenotypic description, and 8 of these were observed by electron microscopy to be peroxisome deficient (Per-). In each per mutant, Mut-, Out-, and Per- phenotypes were tightly linked and therefore were most likely due to a mutation at a single locus. Subcellular fractionation experiments indicated that the peroxisomal marker enzyme catalase was mislocalized to the cytosol in both methanol- and oleate-induced cultures of the mutants. In contrast, alcohol oxidase, a peroxisomal methanol utilization pathway enzyme, was virtually absent from per mutant cells. The relative ease of per mutant isolation in P. pastoris, in conjunction with well-developed procedures for its molecular and genetic manipulation, makes this organism an attractive system for studies on peroxisome biogenesis. PMID- 1629155 TI - Characterization of Pseudomonas putida mutants unable to catabolize benzoate: cloning and characterization of Pseudomonas genes involved in benzoate catabolism and isolation of a chromosomal DNA fragment able to substitute for xylS in activation of the TOL lower-pathway promoter. AB - Mutants of Pseudomonas putida mt-2 that are unable to convert benzoate to catechol were isolated and grouped into two classes: those that did not initiate attack on benzoate and those that accumulated 3,5-cyclohexadiene-1,2-diol-1 carboxylic acid (benzoate diol). The latter mutants, represents by strain PP0201, were shown to lack benzoate diol dehydrogenase (benD) activity. Mutants from the former class were presumed either to carry lesions in one or more subunit structural genes of benzoate dioxygenase (benABC) or the regulatory gene (benR) or to contain multiple mutations. Previous work in this laboratory suggested that benR can substitute for the TOL plasmid-encoded xylS regulatory gene, which promotes gene expression from the OP2 region of the lower or meta pathway operon. Accordingly, structural and regulatory gene mutations were distinguished by the ability of benzoate-grown mutant strains to induce expression from OP2 without xylS by using the TOL plasmid xylE gene (encoding catechol 2,3-dioxygenase) as a reporter. A cloned 12-kb BamHI chromosomal DNA fragment from the P. aeruginosa PAO1 chromosome complemented all of the mutations, as shown by restoration of growth on benzoate minimal medium. Subcloning and deletion analyses allowed identification of DNA fragments carrying benD, benABC, and the region possessing xylS substitution activity, benR. Expression of these genes was examined in a strain devoid of benzoate-utilizing ability, Pseudomonas fluorescens PFO15. The disappearance of benzoate and the production of catechol were determined by chromatographic analysis of supernatants from cultures grown with casamino acids. When P. fluorescens PFO15 was transformed with plasmids containing only benABCD, no loss of benzoate was observed. When either benR or xylS was cloned into plasmids compatible with those plasmids containing only the benABCD regions, benzoate was removed from the medium and catechol was produced. Regulation of expression of the chromosomal structural genes by benR and xylS was quantified by benzoate diol dehydrogenase enzyme assays. The results obtained when xylS was substituted for benR strongly suggest an isofunctional regulatory mechanism between the TOL plasmid lower-pathway genes (via the OP2 promoter) and chromosomal benABC. Southern hybridizations demonstrated that DNA encoding the benzoate dioxygenase structural genes showed homology to DNA encoding toluate dioxygenase from the TOL plasmid pWW0, but benR did not show homology to xylS. Evolutionary relationships between the regulatory systems of chromosomal and plasmid-encoded genes for the catabolism of benzoate and related compounds are suggested. PMID- 1629156 TI - A mutant sigma 32 with a small deletion in conserved region 3 of sigma has reduced affinity for core RNA polymerase. AB - sigma 70, encoded by rpoD, is the major sigma factor in Escherichia coli. rpoD285 (rpoD800) is a small deletion mutation in rpoD that confers a temperature sensitive growth phenotype because the mutant sigma 70 is rapidly degraded at high temperature. Extragenic mutations which reduce the rate of degradation of RpoD285 sigma 70 permit growth at high temperature. One class of such suppressors is located in rpoH, the gene encoding sigma 32, an alternative sigma factor required for transcription of the heat shock genes. One of these, rpoH113, is incompatible with rpoD+. We determined the mechanism of incompatibility. Although RpoH113 sigma 32 continues to be made when wild-type sigma 70 is present, cells show reduced ability to express heat shock genes and to transcribe from heat shock promoters. Glycerol gradient fractionation of sigma 32 into the holoenzyme and free sigma suggests that RpoH113 sigma 32 has a lower binding affinity for core RNA polymerase than does wild-type sigma 32. The presence of wild-type sigma 70 exacerbates this defect. We suggest that the reduced ability of RpoH113 sigma 32 to compete with wild-type sigma 70 for core RNA polymerase explains the incompatibility between rpoH113 and rpoD+. The rpoH113 cells would have reduced amounts of sigma 32 holoenzyme and thus be unable to express sufficient amounts of the essential heat shock proteins to maintain viability. PMID- 1629157 TI - Cloning, nucleotide sequences, and enzymatic properties of glucose dehydrogenase isozymes from Bacillus megaterium IAM1030. AB - Bacillus megaterium is known to have several genes that code for isozymes of glucose dehydrogenase. Two of them, gdhI and gdhII, were cloned from B. megaterium IAM1030 in our previous work (T. Mitamura, R. V. Evora, T. Nakai, Y. Makino, S. Negoro, I. Urabe, and H. Okada, J. Ferment. Bioeng. 70:363-369, 1990). In the present study, two new genes, gdhIII and gdhIV, were isolated from the same strain and their nucleotide sequences were identified. Each gene has an open reading frame of 783 bp available to encode a peptide of 261 amino acids. Thus, a total of four glucose dehydrogenase genes have been cloned from B. megaterium IAM1030. In addition, this strain does not seem to have other glucose dehydrogenase genes that can be distinguished from the four cloned genes so far examined by Southern hybridization analysis. The two newly cloned genes were expressed in Escherichia coli cells, and the products, GlcDH-III and GlcDH-IV, were purified and characterized and compared with the other isozymes, GlcDH-I and GlcDH-II, encoded by gdhI and gdhII, respectively. These isozymes showed different mobilities in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (GlcDH-I greater than GlcDH-III = GlcDH-IV greater than GlcDH-II), although they have the same number of amino acid residues. Double-immunodiffusion tests showed that GlcDH-I is immunologically different from the other isozymes and that GlcDH III and GlcDH-IV are identical to one another but a little different from GlcDH II. These glucose dehydrogenases were stabilized in the presence of 2 M NaCl. The effect of NaCl was especially large for GlcDH-III, which is most unstable enzyme. Kinetic studies showed that these isozymes are divided into two groups with respect to coenzyme specificity, although they can utilize both NAD and NADP: GlcDH-III and GlcDH-IV prefer NAD, and GlcDH-I and GlcDH-II prefer NADP. The phylogenic relationship of these glucose dehydrogenase genes is also discussed. PMID- 1629158 TI - Light and oxygen regulation of the synthesis of bacteriochlorophylls a and c in Chloroflexus aurantiacus. AB - Control of the synthesis of bacteriochlorophylls (Bchls) a and c by light and oxygen was studied in Chloroflexus aurantiacus grown in batch or chemostat culture with serine as the growth-limiting substrate. For comparison, inhibition by gabaculine of the formation of selected tetrapyrroles was studied. The inhibitory effect of gabaculine decreased in the following order of tetrapyrrole formation: coproporphyrin greater than Bchl c greater than Bchl a. Not only did addition of 5-aminolevulinate (ALA) reverse the inhibition by gabaculine, it also caused an increase in Bchl c content when the cultures grew at high concentrations of ALA. Inhibition of Bchl a, Bchl c, and coproporphyrin formation by oxygen was similar to inhibition by gabaculine. Addition of ALA to aerated cultures led to significant accumulation of coproporphyrin. These results suggest that oxygen inhibits tetrapyrrole formation at a site before ALA formation. Control by light was studied with chemostat cultures transferred from 5 klx to 25 klx. This resulted in only a transient increase of the protein level of the culture, while specific contents of Bchls c and a and the ratio Bchl c/Bchl a decreased to lower steady states. However, the specific content of coproporphyrin increased. Addition of ALA to chemostat cultures adapted to 50 klx increased specific coproporphyrin and Bchl c contents by factors of about 20 and 4, respectively, while the specific Bchl a content was only slightly increased and protein levels were unaffected. Increasing the serine concentration caused an initial increase in the specific Bchl c content, which returned to the original value as soon as the protein content had attained its maximal level. These results suggest that light does not control ALA formation as strictly as oxygen and that competition of biomass formation and tetrapyrrole synthesis for common precursors may be influenced by light. PMID- 1629159 TI - Osmoprotection of Escherichia coli by ectoine: uptake and accumulation characteristics. AB - Ectoine (1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) is a cyclic amino acid, identified as a compatible solute in moderately halophilic bacteria. Exogenously provided ectoine was found to stimulate growth of Escherichia coli in media of inhibitory osmotic strength. The stimulation was independent of any specific solute, electrolyte or nonelectrolyte. It is accumulated in E. coli cells proportionally to the osmotic strength of the medium, and it is not metabolized. Its osmoprotective ability was as potent as that of glycine betaine. The ProP and ProU systems are both involved in ectoine uptake and accumulation in E. coli. ProP being the main system for ectoine transport. The intracellular ectoine pool is regulated by both influx and efflux systems. PMID- 1629160 TI - Lignin peroxidase gene family of Phanerochaete chrysosporium: complex regulation by carbon and nitrogen limitation and identification of a second dimorphic chromosome. AB - Lignin peroxidases (LiP) of Phanerochaete chrysosporium are encoded by a family of six closely related genes. Five LiP genes have been localized to the same dimorphic chromosome. In this investigation, relative transcript levels of the LiP genes were determined. Transcripts of the LiPA, LiPB, and O282 genes were at similar levels in both carbon- and nitrogen-limited cultures. In contrast, transcription of the GLG5, V4, and GLG4 genes was dramatically altered by culture conditions. Under carbon-limited conditions, GLG4 transcripts were, by far, the most abundant. Southern blot analyses of clamped homogeneous field gels were used to map the GLG4 gene to a dimorphic chromosome separate from the other LiP genes. PMID- 1629161 TI - Production and characterization of a monoclonal antibody to the O-acetylated peptidoglycan of Proteus mirabilis. AB - A monoclonal antibody (PmPG5-3) specific for the O-acetylated peptidoglycan of Proteus mirabilis 19 was produced by an NS-1 myeloma cell line and purified from ascites fluid by a combination of ammonium sulfate precipitation and affinity chromatography. The monoclonal antibody (an immunoglobulin M) was characterized by a competition enzyme-linked immunosorbent assay to be equally specific for both insoluble and soluble O-acetylated peptidoglycan but weakly recognized chemically de-O-acetylated P. mirabilis peptidoglycan, the non-O-acetylated peptidoglycans from Escherichia coli and Bacillus subtilis, and the peptidoglycan monosaccharide precursors N-acetylglucosamine and N-acetylmuramic acid dipeptide. The monoclonal antibody did not react with D-alanine or lipopolysaccharide isolated from P. mirabilis. Based on this evidence, the binding epitope on the P. mirabilis peptidoglycan is predicted to be linear and to comprise the glycan backbone, including both the N- and O-acetyl moieties. Monoclonal antibody PmPG5 3 was used to localize the O acetylation of the P. mirabilis peptidoglycan by immunoelectron microscopy. Murein sacculi of P. mirabilis were heavily and randomly labelled with the immunogold, whereas very little labelling and no labelling were observed on the sacculi isolated from de-O-acetylated P. mirabilis and E. coli, respectively. Based on the apparent pattern of immunogold labelling, a physiological role for peptidoglycan O acetylation in P. mirabilis is proposed. PMID- 1629162 TI - Menaquinone (vitamin K2) biosynthesis: nucleotide sequence and expression of the menB gene from Escherichia coli. AB - In Escherichia coli, the biosynthesis of the electron carrier menaquinone (vitamin K2) involves at least seven identified enzymes. One of these, naphthoate synthase, forms the bicyclic ring system by catalyzing the conversion of o succinylbenzoyl-coenzyme A to 1,4-dihydroxy-2-naphthoic acid. The gene for this enzyme has been previously identified as menB. By genetic and biochemical tests, a 1.349-kb DNA fragment from the E. coli men locus complements menB mutants. This fragment contains a single 285-codon open reading frame (ORF). Recombinant plasmids containing deletions of either the amino or the carboxy region of the ORF fail to complement the mutants. The ORF is preceded by consensus sequences for a ribosomal binding site and a sigma 70 promoter. menB transcription sufficient to complement the menB mutant in vivo and in vitro can be initiated from the identified putative promoter, and that in the constructs, menB expression, can be made independent of read-through transcription from the lac promoter. However, multicopy plasmids containing menB fail to generate the expected levels of enzymatic activity. PMID- 1629163 TI - Sequence organization and regulation of the Bacillus subtilis menBE operon. AB - Menaquinone (MK) plays a central role in the respiratory chain of Bacillus subtilis. The biosynthesis of MK requires the formation of a naphthoquinone ring via a series of specific reactions branching from the shikimate pathway. "Early" MK-specific reactions catalyze the formation of o-succinylbenzoate (OSB) from isochorismate, and "late" reactions convert OSB to dihydroxynaphthoate, by utilizing an OSB-coenzyme A intermediate. We have cloned and sequenced the B. subtilis menE and menB genes encoding, respectively, OSB-coenzyme A synthase and dihydroxynaphthoate synthase. The MenB open reading frame encodes a potential polypeptide of 261 amino acid residues with a predicted size of 28.5 kDa, while the MenE open reading frame could encode a 24.4-kDa polypeptide of 220 amino acid residues. Probable promoter sequences were identified by high-resolution primer extension assays. Organization of these genes and regulatory regions was found to be menBp menB menEp menE. Expression of menE was dependent on both menEp and menBp, indicating an operonlike organization. A region of dyad symmetry capable of forming a stable RNA secondary structure was found between menB and menE. Culture cycle-dependent expression of menB and menE was measured by steady-state transcript accumulation. For both genes, maximal accumulation was found to occur within an hour after the end of exponential growth. The menBp and menEp promoters have sequences compatible with recognition by the major vegetative form of B. subtilis RNA polymerase, E sigma A. Both promoter regions also were found to contain homologies to a sequence motif previously identified in the menCDp region and in promoters for several B. subtilis tricarboxylic acid cycle genes. PMID- 1629164 TI - Occurrence of novel groups of the domain Bacteria as revealed by analysis of genetic material isolated from an Australian terrestrial environment. AB - A molecular ecological study was performed on an Australian soil sample to unravel a substantial portion of the bacterial diversity. A large fragment of the 16S rRNA gene was amplified, using DNA isolated by lysing the microorganisms directly within the soil matrix, and a clone library was generated. Comparative sequence analysis of 30 clones and dot blot hybridization of 83 additional clones with defined oligonucleotide probes revealed the presence of three major groups of prokaryotes of the domain Bacteria. The first one comprises 57 clones that indicate relatives of nitrogen-fixing bacteria of the alpha-2 subclass of the class Proteobacteria; the second group of 7 clones originates from members of the order Planctomycetales that, however, reveal no close relationship to any of the described Planctomycetales species; 22 clones of the third group are indicative of members of a novel main line of descent, sharing a common ancestry with members of planctomycetes and chlamydiae. PMID- 1629165 TI - In vitro activation of the Serratia marcescens hemolysin through modification and complementation. AB - The hemolytic activity of Serratia marcescens is determined by two polypeptides, termed ShlA and ShlB. ShlA is synthesized as an inactive precursor (ShlA*) and secreted with the help of ShlB, which is located in the outer membrane. In this study, it is shown that a cell lysate containing ShlB as well as partially purified ShlB converted ShlA* to the active ShlA hemolysin. ShlA remained active after removal of ShlB by column chromatography. In contrast to the stable modification of ShlA* by ShlB, a reversible activation was achieved by adding to ShlA* an N-terminal fragment of ShlA (ShlA16), consisting of 269 amino acid residues of ShlA and 18 residues of the vector. The nonhemolytic ShlA16 complemented ShlA* only when it was synthesized in an ShlB-producing cell. A deletion derivative of ShlA*, lacking residues 4 to 117, was complemented by ShlA16 but not activated by ShlB. Activation of ShlA* by ShlB at 4 degrees C proceeded at a much slower rate than complementation by ShlA16. It is concluded that ShlA* is modified by ShlB. ShlA16 modified by ShlB complements the missing modification of ShlA* in trans. Modification by ShlB occurs in the N-terminal part of ShlA*, which is also the reaction in vivo which results in active ShlA hemolysin in the culture supernatant. The HpmA hemolysin of Proteus mirabilis, which is very similar to ShlA, was also activated in vitro by ShlB and complemented by ShlA16. PMID- 1629166 TI - Alkaline pH decreases expression of the accessory gene regulator (agr) in Staphylococcus aureus. AB - The effect of alkaline pH on expression of the accessory gene regulator (agr) in Staphylococcus aureus was examined. agr, a global regulator, affects the expression of numerous exoproteins, including alpha-hemolysin, toxic shock syndrome toxin 1, protein A, and staphylococcal enterotoxins types B, C, and D. agr contains two major, divergent transcripts, designated RNAII and RNAIII. In this study, the level of RNAIII was used to monitor agr expression because this transcript and/or its protein product(s) appears to be responsible for altering target gene expression. S. aureus FRI1230 and its Agr- derivative were examined in a fermentor system which allowed batch cultures to be maintained at a constant pH. FRI1230 cultures were grown at pH 6.5, 7.0, 7.5, and 8.0. Northern (RNA blot) analysis of samples revealed that maximal agr expression occurred at pH 7.0, with virtually no RNAIII observed at pH 8.0. The effect of alkaline pH on an agr target gene, sec, was also evaluated. sec expression was reduced at alkaline pH in strain FRI1230 (Agr+) but not in its Agr- derivative, indicating that an intact agr allele is required for the pH effect on sec. Examination of batch cultures under conditions of nonmaintained pH gave results that were also consistent with a role for alkaline pH in repressing agr expression. PMID- 1629167 TI - Anaerobic control of colicin E1 production. AB - Expression of the cea gene, which is carried by the ColE1 plasmid and which encodes colicin E1, was found to be greatly increased when the cells were grown anaerobically. By using cea-lacZ fusions to quantitate expression, aerobic levels were found to be only a few percent of the anaerobic levels. The anaerobic increase in expression was observed both in protein and in operon fusions, indicating that its regulation occurred at the level of transcription. It was also found to require a functional fnr gene and to occur when the cea-lacZ fusion was present as a single copy in the bacterial chromosome instead of in the multicopy ColE1 plasmid. Anaerobic expression was regulated by the SOS response and catabolite repression as is aerobic expression. The start site of the mRNA produced under anaerobic conditions was mapped by primer extension and found to be the same as the start for mRNA produced under aerobic conditions. These observations show that the cea gene is anaerobically regulated and that the Fnr protein is a positive regulator of transcription of this gene. PMID- 1629168 TI - Interaction of LexA repressor with the asymmetric dinG operator and complete nucleotide sequence of the gene. AB - The dinG gene was originally isolated during a search for Escherichia coli promoters which are components of the SOS regulon. The regulatory region of this gene contains a potential binding site for LexA repressor which is quite different from other known sites. All previously described chromosomal LexA operators are imperfect palindromes containing the sequence CTG(N10)CAG. The noncanonical dinG sequence breaks the symmetry and takes the form TTG(N10)CAG. In the present study, a search for mutations within dinGop::galK fusion plasmids which render transcription independent of intracellular levels of LexA has yielded mutations only within this 16-bp sequence. Electrophoretic mobility shift assays performed with purified mutant and wild-type operator fragments revealed that the affinity of LexA for each of the mutant sites is greatly reduced compared with that of the wild type. One of the mutants contained an alteration in the putative promoter of dinG which increased the similarity of the -35 region to the consensus sequence (TTGGCT----TTGACT); the apparent promoter activity of this construct was subsequently found to be approximately eight times higher than that of the wild type in vivo. Additional experiments have established the complete nucleotide sequence of the dinG gene. A long open reading frame located immediately downstream of the asymmetric operator segment which could potentially encode a 72.9-kDa DinG protein was identified. PMID- 1629169 TI - Membrane ultrastructure of alkaliphilic Bacillus species studied by rapid-freeze electron microscopy. AB - Cells of Bacillus firmus OF4 and Bacillus alcalophilus were examined by rapid freeze freeze-fracture and freeze-substitution electron microscopy. No special vesicular structures linked to growth at alkaline pH were found, either within or associated with the cytoplasmic membrane. The cytoplasmic membranes of the alkaliphilic bacilli and the neutrophilic Bacillus subtilis BD99 were indistinguishable. Distinctive intramembrane particle rings, presumed to be flagellar structures on the basis of distribution and morphological characteristics, were found in all of these species. These observations indicate that the adaptations required to effect oxidative phosphorylation and flagellar rotation at extreme alkaline pH occur without gross morphological rearrangement. PMID- 1629170 TI - Homology among Escherichia coli K1 and K92 polysialytransferases. AB - The neuS-encoded polysialytransferase (polyST) in Escherichia coli K1 catalyzes synthesis of polysialic acid homopolymers composed of unbranched sialyl alpha 2,8 linkages. Subcloning and complementation experiments showed that the K1 neuS was functionally interchangeable with the neuS from E. coli K92 (S. M. Steenbergen, T. J. Wrona, and E. R. Vimr, J. Bacteriol. 174:1099-1108, 1992), which synthesizes polysialic acid capsules with alternating sialyl alpha 2,8-2,9 linkages. To better understand the relationship between these polySTs, the complete K92 neuS sequence was determined. The results demonstrated that K1 and K92 neuS genes are homologous and indicated that the K92 copy may have evolved from its K1 homolog. Both K1 and K92 structural genes comprised 1,227 bp. There were 156 (12.7%) differences between the two sequences; among these mutations, 55 did not affect the derived primary structure of K92 polyST and hence were synonymous with the K1 sequence. Assuming maximum parsimony, another estimated 17 synonymous mutations plus 84 nonsynonymous mutations could account for the 70 amino acid replacements in K92 polyST; 36 of these replacements were judged to be conservative when compared with those of K1 polyST. There were no changes detected in the first 146 5' or last 129 3' bp of either gene, suggesting, in addition to the observed mutational differences, the possibility of a past recombination event between neuS loci of two different kps clusters. The results indicate that relatively few amino acid changes can account for the evolution of a glycosyltransferase with novel linkage specificity. PMID- 1629171 TI - Production of an extracellular milk-clotting activity during development in Myxococcus xanthus. AB - We describe here an extracellular proteolytic activity secreted during both growth and submerged development by Myxococcus xanthus DK1622. This activity yields the clotting of kappa-casein at pH 6 and is inhibited by specific inhibitors of aspartic proteases. Secretion of this milk-clotting proteolytic activity (of Mcp) is time regulated during the developmental cycle, with a large increase near 9 h poststarvation, but its production does not require cell-cell contact. The lack of secretion of this activity by several developmental mutants in submerged development conditions shows that Mcp production is developmentally regulated. PMID- 1629172 TI - A macrolide 3-O-acyltransferase gene from the midecamycin-producing species Streptomyces mycarofaciens. AB - The Streptomyces mycarofaciens mdmB gene encodes a 3-O-acyltransferase that catalyzes the addition of acetyl and propionyl groups to position 3 of the lactone ring in 16-member macrolide antibiotics like midecamycin and spiramycin. A putative O-methyltransferase gene (mdmC) is immediately downstream of mdmB, and both of these genes are closely linked to the mdmA midecamycin resistance gene. PMID- 1629173 TI - Phosphate taxis in Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa was shown to be attracted to phosphate. The chemotactic response was induced by phosphate starvation. The specificity of chemoreceptors for phosphate was high so that no other tested phosphorus compounds elicited a chemotactic response as strong as that elicited by phosphate. Competition experiments showed that the chemoreceptors for phosphate appeared to be different from those for the common amino acids. Mutants constitutive for alkaline phosphatase showed the chemotactic response to phosphate regardless of whether the cells were starved for phosphate. PMID- 1629174 TI - Altered murein composition in a DD-carboxypeptidase mutant of Streptococcus pneumoniae. AB - The muropeptide composition of a Streptococcus pneumoniae mutant in which the DD carboxypeptidase (penicillin-binding protein 3) gene was interrupted by plasmid insertion close to the 3' end of the gene was examined. Extensive compositional changes were observed: the linear pentapeptide, a minor component of the parental cells, became the most abundant monomeric peptide in the mutant wall, while the proportion of tripeptides that represent the main monomers in the parental cells was greatly reduced. The amount of the major dimer of parental cells, the directly cross-linked tri-tetrapeptide, was also reduced by a factor of 4. It was partially replaced by a novel dimer: the cross-linked product of a linear pentapeptide and a pentapeptide carrying a serylalanine dipeptide substituent on the epsilon-NH2 group of its lysine residue. This dimer together with two other dimeric peptides, each containing the serylalanine cross bridge, became the quantitatively major components of the mutant peptidoglycan. PMID- 1629175 TI - Activation defects caused by mutations in Escherichia coli rpoA are promoter specific. AB - Escherichia coli RNA polymerases containing mutated alpha subunits were tested for their ability to respond to three different positive regulators (activators) in vitro. The two alpha (rpoA) mutants, alpha-256 and alpha-235, have deletions of the C-terminal 73 and 94 amino acids, respectively. In runoff transcription assays catalyzed by reconstituted holoenzyme, the effects of the mutations on each of three promoters tested were different: activation of the lambda pRM promoter by cI protein (repressor) was nearly normal, activation of the lambda pRE promoter by cII protein was reduced approximately fivefold, and direct activation of the trpPB promoter of Pseudomonas aeruginosa was completely inhibited. We also found that the reconstituted mutant enzyme was defective in recognition of trpPI in the absence of activator. The differential responses of the three promoters to their activators in the presence of the mutant enzymes indicate that the location of an activator-binding site does not by itself determine the region of RNA polymerase with which the activator interacts. PMID- 1629177 TI - Construction and characterization of Streptomyces coelicolor A3(2) mutants that are multiply deficient in the nonessential hrd-encoded RNA polymerase sigma factors. AB - Previous studies showed that Streptomyces coelicolor A3(2) has four genes (hrdA, hrdB, hrdC, and hrdD) that appear to encode RNA polymerase sigma factors very similar to the sigma 70 subunit of Escherichia coli and that hrdC and hrdD could be individually disrupted without causing obvious phenotypic defects. Here, hrdA was cloned and stable null hrdA and hrdD mutants were constructed by gene replacement. These two mutants and a previously constructed hrdC null mutant were used in crosses to generate hrdAC, hrdAD, hrdCD, and hrdACD strains. The inability to synthesize one, two, or all three of the nonessential hrd-encoded sigma factors had no obvious phenotypic consequences. PMID- 1629176 TI - The Agrobacterium tumefaciens virD3 gene is not essential for tumorigenicity on plants. AB - Genetic studies indicate that three of the four polypeptides encoded within the virD operon of the Agrobacterium tumefaciens Ti plasmid are essential for virulence. In order to determine whether the fourth polypeptide, VirD3, has any role in virulence, complementation analysis was used. An A. tumefaciens strain, A348 delta D, which lacked the entire virD operon in the Ti plasmid pTiA6, was constructed. Plasmids containing defined regions of the virD operon were introduced into this strain, and virulence was tested by the strains' abilities to form tumors on Kalanchoe leaves, tomato stems, and potato tubers. As expected, deletion of the virD operon led to an avirulent phenotype. The virulence of this strain could be restored by providing virD1, virD2, and virD4 in trans. No requirement for virD3 in tumor formation was observed in these assays. PMID- 1629178 TI - A general method for cloning recA genes of gram-positive bacteria by polymerase chain reaction. AB - An internal fragment of the recA gene from eight gram-positive organisms has been amplified by using degenerate primers in a polymerase chain reaction. The internal 348- or 360-bp recA DNA segments from Bacillus subtilis, Clostridium acetobutylicum, Lactobacillus bulgaricus, Lactobacillus helveticus, Leuconostoc mesanteroides, Listeria monocytogenes, Staphylococcus aureus, and Streptococcus salivarus subsp. thermophilus were amplified, cloned, and sequenced. The G + C contents of the DNA from these species range from 28 to 52%. The sequences of the bacterial recA genes show strong relatedness. This method is particularly useful for the recovery of the recA genes of gram-positive bacteria and avoids the difficulties of using a genetic complementation test for cloning. PMID- 1629179 TI - mRNP4, a major mRNA-binding protein from Xenopus oocytes is identical to transcription factor FRG Y2. AB - Previous work has revealed a striking similarity between the sequence of mRNP4, a major mRNA-binding protein of Xenopus laevis oocytes and FRG Y2, a transcription factor specific for Y-box-containing promoters. However, the apparent molecular mass of mRNP4 exceeds by 50-60% the cDNA-deduced molecular mass of FRG Y2. To resolve this discrepancy we have measured the real molecular mass of mRNP4 by sedimentation equilibrium. The molecular mass of mRNP4 closely agrees with that of FRG Y2. We conclude that mRNP4 is identical to FRG Y2 and has a dual function in oocytes. As a DNA-binding protein, mRNP4 stimulates transcription from a specific set of promoters. As a mRNA-binding protein, mRNP4 favors accumulation of the transcripts it contributes to produce. PMID- 1629180 TI - The matrix metalloproteinase pump-1 catalyzes formation of low molecular weight (pro)urokinase in cultures of normal human kidney cells. AB - The enzyme responsible for the metalloproteinase activity which cleaves the Glu143-Leu144 bond of (pro)urokinase has been isolated from the conditioned medium of cultured normal human kidney cells. Using S-Sepharose and Cibacron Blue agarose chromatography, then C-4 reversed phase high pressure liquid chromatography, a protein of about 20,000 Da was isolated. Through an identical amino-terminal sequence, the protein was shown to be the matrix metalloproteinase previously referred to in the literature as "pump-1" (putative metalloproteinase). When aprotinin was added during the course of the purification, the major species isolated was the zymogen form (28,000 Da) of pump 1. Pump-1 has been shown to efficiently cleave the susceptible bond of both pro urokinase (single-chain) and active (two-chain) urokinase and thereby produce the corresponding low molecular weight forms. The amino-terminal sequences of the A and B chains of low molecular weight urokinase prepared by action of pump-1 on recombinant high molecular weight urokinase are identical to those of the low molecular weight urokinase isolated from human kidney cell culture. Since the reaction of urokinase with this metalloproteinase results in separation of its serine proteinase region from the domain which mediates binding to the urokinase receptor, it may be of importance in the regulation of the functional activity of the plasminogen activator in cellular processes. PMID- 1629181 TI - Specificity of G protein beta and gamma subunit interactions. AB - Multiple heterotrimeric guanine nucleotide binding protein (G protein) subunits have evolved to couple a large variety of receptors to intracellular effectors. G protein beta gamma subunits are essential for efficient coupling of alpha subunits to receptors, and they are also important for modulation of effectors. Several different beta and gamma subunits exist, but it is not known whether all possible combinations of beta and gamma can form functional dimers. To answer this question, we have compared the ability of in vitro translated beta 1, beta 2, and beta 3 to form dimers with either gamma 1 or gamma 2. Dimerization was monitored by gel filtration, resistance to tryptic digestion, and chemical cross linking. The results indicate that beta 1 binds both gamma subunits, beta 2 binds only gamma 2, and beta 3 will bind neither gamma 1 or gamma 2. Hence, the occurrence of beta gamma dimers may be partially regulated by the ability of the subunits to associate. Specificity of dimerization might allow cells to co express multiple beta and gamma subunits while maintaining efficient and specific signal transduction. PMID- 1629182 TI - Rapid assembly and disassembly of complementary DNA strands through an equilibrium intermediate state mediated by A1 hnRNP protein. AB - A1 hnRNP protein, which rapidly renatures complementary strands of nucleic acids in vitro, affects both the equilibrium and kinetic properties of the reaction (single-stranded DNA in equilibrium with double-stranded DNA). A1 lowers the melting transition of duplex DNA. However, at temperatures above this new Tm, both single- and double-stranded DNAs are present at equilibrium and are rapidly interconverting. Although the ratio of single and double strands under these conditions is a function of both the A1 protein and complementary DNA strand concentrations, it is not strongly affected by further increases in temperature. These surprising results demonstrate that A1 does not act as a simple catalyst in promoting renaturation and indicate how A1 and other proteins could act to speed the turnover of intermediate complexes in important biological processes. PMID- 1629183 TI - Chondroitin sulfate proteoglycan form of the Alzheimer's beta-amyloid precursor. AB - The Alzheimer's amyloid beta protein is derived from a family of membrane glycoproteins termed amyloid precursor proteins (APP). Here we show that APP exists as the core protein of a chondroitin sulfate (CS) proteoglycan, ranging in apparent molecular size from 140 to 250 kDa, secreted by glial cell line C6. After partial purification on ion-exchange and gel chromatography, the secreted APP proteoglycan was recognized on Western blots by several antibodies specific to different regions of APP. Chondroitinase AC or ABC treatment of our samples completely eliminated the high molecular weight proteoglycan with a concomitant increase in the APP protein. This digested product reacted with an anti-stub antibody which recognizes 4-sulfated disaccharide. Sequencing of the N terminus of the core protein of this CS proteoglycan yielded 18 residues identical to the N terminus sequence of the mature APP. Quantitative analysis showed that, in this cell line, about 90% of the secreted nexin II form of APP occurs in the proteoglycan form, suggesting that the CS chains have a role in the biological function of this protein. The close proximity of two consensus CS attachment sites to both the N terminus of the amyloid beta protein and the secretase cleavage site, suggests that the CS chains may affect the proteolysis of APP and production of the amyloid beta protein. PMID- 1629184 TI - U73122 inhibits Ca2+ oscillations in response to cholecystokinin and carbachol but not to JMV-180 in rat pancreatic acinar cells. AB - Stimulation of rat pancreatic acinar cells with low concentrations of phosphatidylinositol (PI)-linked secretagogues induces [Ca2+]i oscillations, without measurable changes in the formation of inositol 1,4,5-trisphosphate. Therefore, we tested U73122 a new phospholipase C inhibitor to determine if PI turnover is necessary for the generation of [Ca2+]i oscillations. In acini prelabeled with [3H]inositol, PI hydrolysis on stimulation with either cholecystokinin or carbachol was inhibited dose-dependently by U73122, with a maximal effect seen at 10 microM; the formation of inositol 1,4,5-trisphosphate, measured using a radioreceptor assay, was also similarly inhibited. By contrast secretin- or vasoactive intestinal peptide-stimulated production of cAMP was unaffected by 10 microM U73122. These studies indicate that U73122 is a relatively specific inhibitor of G-protein-mediated phospholipase C activation in pancreatic acini. In fura-2-loaded acini, U73122 inhibited the increases in [Ca2+]i stimulated by these high concentrations of secretagogues which can be demonstrated to elicit PI turnover. The [Ca2+]i signal generated by directly stimulating G-proteins with sodium fluoride was also inhibited by U73122; however, the [Ca2+]i rise induced by thapsigargin was unaffected. These data indicate that the mechanism of inhibition was distal to the occupation of cell surface receptors but did not involve an interference of Ca2+ metabolism in general. When [Ca2+]i oscillations were elicited by low concentrations of cholecystokinin or carbachol, U73122 rapidly inhibited the oscillating [Ca2+]i signal. In contrast, oscillations induced by an analogue of cholecystokinin, JMV 180, which does not stimulate changes in PI metabolism at any concentration, were unaffected. This indicates that cholecystokinin- and carbachol-induced oscillations are probably initiated by small, localized changes in PI metabolism, which are not readily detectable. However, the inability of U73122 to inhibit JMV 180-induced oscillations indicates that PI metabolism may not necessarily be a prerequisite for the generation of [Ca2+]i oscillations. PMID- 1629185 TI - Deletion of lactose repressor carboxyl-terminal domain affects tetramer formation. AB - The carboxyl-terminal sequence of the lac repressor protein contains heptad repeats of leucines at positions 342, 349, and 356 that are required for tetramer assembly, as substitution of these leucine residues yields solely dimeric species (Chakerian, A. E., Tesmer, V. M., Manly, S. P., Brackett, J. K., Lynch, M. J., Hoh, J. T., and Matthews, K. S. (1991) J. Biol. Chem. 266, 1371-1374; Alberti, S., Oehler, S., von Wilcken-Bergmann, B., Kramer, H., and Muller-Hill, B. (1991) New Biol. 3, 57-62). To further investigate this region, which may form a leucine zipper motif, a family of lac repressor carboxyl-terminal deletion mutants eliminating the last 4, 5, 11, 18, and 32 amino acids (aa) has been constructed. The -4 aa mutant, in which all of the leucines in the presumed leucine zipper are intact, is tetrameric and displays operator and inducer binding properties similar to wild-type repressor. The -5 aa, -11 aa, -18 aa, and -32 aa deletion mutants, depleted of 1, 2, or all 3 of the leucines in the heptad repeats, are all dimeric, as demonstrated by gel filtration chromatography. Circular dichroism spectra and protease digestion studies indicate similar secondary/tertiary structures for the mutant and wild-type proteins. Differences in reaction with a monoclonal antibody specific for a subunit interface are observed for the dimeric versus tetrameric proteins, indicative of exposure of the target epitope as a consequence of deletion. Inducer binding properties of the deletion mutants are similar to wild-type tetrameric repressor at neutral pH. Only small differences in affinity and cooperativity from wild-type are evident at elevated pH; thus, the cooperative unit within the tetramer appears to be the dimer. "Apparent" operator binding affinity for the dimeric proteins is diminished, although minimal change in operator dissociation rate constants was observed. The diminution in apparent operator affinity may therefore derive from either 1) dissociation of the dimeric mutants to monomer generating a linked equilibrium or 2) alterations in intrinsic operator affinity of the dimers; the former explanation is favored. This detailed characterization of the purified mutant proteins confirms that the carboxyl-terminal region is involved in the dimer dimer interface and demonstrates that cooperativity for inducer binding is contained within the dimer unit of the tetramer structure. PMID- 1629186 TI - Prostaglandin endoperoxide synthase substituted with manganese protoporphyrin IX. Formation of a higher oxidation state and its relation to cyclooxygenase reaction. AB - The heme in prostaglandin endoperoxide synthase (PGH synthase) was substituted with Mn(III)-protoporphyrin IX. The resulting enzyme, Mn-PGH synthase, showed full cyclooxygenase activity but only 0.9% of the peroxidase activity of the native iron enzyme. During the reaction with exogenous or endogenously produced hydroperoxides, a spectral intermediate of Mn-PGH synthase was observed. The electronic absorption bands of the resting enzyme at 376, 472, and 561 nm decreased, and the intermediate's bands at 417, around 513, and 625 nm appeared. The rate constant of the formation of the intermediate was about 10(4) M-1.s-1 at 22 degrees C, three orders of magnitude lower than with the iron enzyme. Spectral properties, conditions of formation, and the suppressed formation in the presence of electron donors provide evidence for a higher oxidation state of Mn-PGH synthase, tentatively a Mn(IV) species. This species was assigned to an intermediate in the peroxidase reaction of Mn-PGH synthase, the low activity of which was explained by the rate-limiting slow reaction of Mn-PGH synthase with hydroperoxides. The findings and interpretation are consistent with the published properties of other manganese-substituted peroxidases. Although the cyclooxygenase activity was similar to that of Fe-PGH synthase, the cyclooxygenase reaction of Mn-PGH synthase showed distinct differences in comparison with Fe-PGH synthase. A longer activation phase was observed which resembled the time course of the formation of the higher oxidation state. Glutathione peroxidase with glutathione, a hydroperoxide-scavenging system, inhibited the cyclooxygenase of Mn-PGH synthase at concentrations where the activity of Fe-PGH synthase was not affected. It is demonstrated that Mn-PGH synthase requires higher concentrations of hydroperoxides for the activation of the cyclooxygenase. These findings suggest that the substitution of iron with manganese in PGH synthase does not change the mechanism of the enzyme. The main difference is the much lower rate of the reaction with hydroperoxides which affects both the peroxidase activity and the hydroperoxide-dependent activation of the cyclooxygenase. A reaction scheme for Mn-PGH synthase is proposed analogous to that suggested for Fe-PGH synthase (Karthein, R., Dietz, R., Nastainczyk, W., and Ruf, H. H. (1988) Eur. J. Biochem. 171, 313-320). PMID- 1629187 TI - Differentiation-dependent expression of retinoid-binding proteins in BFC-1 beta adipocytes. AB - Recently, we demonstrated that adipose tissue plays an important role in retinol storage and retinol-binding protein (RBP) synthesis. Our data suggested that RBP expression in adipose tissue is dependent on the state of adipocyte differentiation. To examine this possibility, we explored the differentiation dependent expression of RBP using BFC-1 beta preadipocytes, which can be stimulated to undergo adipose differentiation. Total RNA was isolated from undifferentiated (preadipocytes) and differentiated (adipocytes) BFC-1 beta cells and analyzed by Northern blotting. RBP mRNA was not detected in the preadipocytes, but considerable RBP mRNA was present in differentiated BFC-1 beta cells. In BFC-1 beta cells, induced to differentiate with insulin and thyroid hormone, RBP mRNA was first detected after 4 days, reached a maximum level by day 10, and remained at this maximum level for at least 2 more days. Cellular retinol binding protein was expressed at low levels in the BFC-1 beta preadipocytes and the level of expression increased for 6 days after induction to differentiate and slowly declined on later days. Neither the maximum level of RBP expression nor the day on which this level was reached was influenced by the level of retinol provided in the BFC-1 beta culture medium. BFC-1 beta cells secreted newly synthesized RBP into the culture medium at a rate of 43 +/- 14 ng RBP/24 h/10(6) adipocytes. When the BFC-1 beta adipocytes were provided 1.0 microM retinol in the medium, they accumulated the retinol and synthesized retinyl esters. These studies with BFC-1 beta cells confirm that RBP synthesis and secretion and retinol accumulation are intrinsic properties of differentiated adipocytes. Furthermore, they suggest that RBP and cellular retinol-binding protein gene expression are regulated as part of a package of genes which are modulated during adipocyte differentiation. PMID- 1629188 TI - Identification of TIMP-2 in human alveolar macrophages. Regulation of biosynthesis is opposite to that of metalloproteinases and TIMP-1. AB - We have identified the metalloproteinase inhibitor TIMP-2 as a secreted product of human alveolar macrophages. In contrast to human fibroblasts, TIMP-2 was released from macrophages free of any apparent complexed metalloproteinases. Also in marked distinction to fibroblasts, TIMP-2 secretion from mononuclear phagocytes was subject to modulation by a variety of agents. TIMP-2 was synthesized by macrophages placed in culture under basal conditions in amounts approximately 30% of those secreted by fibroblasts on a per cell basis. The additions of lipopolysaccharide, denatured type I collagen, and zymosan to culture medium each resulted in a dose-dependent and profound decrease in macrophage TIMP-2 protein production and steady-state mRNA levels. In contrast, all of these agents markedly enhanced the biosynthesis of macrophage interstitial collagenase and TIMP-1 as assessed by analysis of identical cell and conditioned media samples. In human fibroblasts, TIMP-2 biosynthesis was unaffected by interleukin-1, tumor necrosis factor-alpha, platelet-derived growth factor, and phorbol ester despite the massive collagenase stimulation induced by each of these agents. We conclude that TIMP-2 is a potentially important mononuclear phagocyte product whose biosynthesis is regulated in a distinct and completely opposite manner to that of collagenase and TIMP-1. PMID- 1629189 TI - Ligand binding specificity of the leukocyte response integrin expressed by human neutrophils. AB - The ligand binding specificity of the leukocyte response integrin (LRI) expressed by polymorphonuclear leukocyte (PMN) was investigated by examining its interaction with two adhesion motifs within fibrinogen: the alpha chain sequence RGD and the gamma chain sequence KQAGDV. The effect of the hexapeptides KQAGDV, KQRGDV, and KGAGDV on fibrinogen-stimulated phagocytosis, a LRI-dependent function, was examined. Surprisingly, the sequence KGAGDV was most potent for inhibition of fibrinogen-stimulated ingestion; the order of potency of these peptides was KGAGDV greater than KQAGDV greater KQRGDV = GRGDSPA. Latex spheres coated with multivalent KGAGDV bound specifically to PMN and antibodies that recognized either the LRI beta chain (7G2) or an associated protein (IAP) abrogated bead binding. Various control and anti-beta 1 and anti-beta 2 antibodies did not affect bead binding. Monovalent peptides KGAGDV and KQRGDV were equipotent for inhibition of bead binding to unstimulated PMN (ID50 = 19 microM). In contrast, KGAGDV was more potent than KQRGDV for inhibition of bead binding to N-formylmethionylleucylphenylalanine-stimulated PMN (ID50 = 2.5 microM versus ID50 = 60 microM). A control peptide, KGALEVA, did not inhibit LRI ligand binding or function. These data suggest that the unique amino acid sequence KGAGDV may represent a specific ligand for LRI and that LRI ligand binding specificity may be regulated by the activation state of the cell. PMID- 1629190 TI - Regulation of intracellular pH values in higher plant cells. Carbon-13 and phosphorus-31 nuclear magnetic resonance studies. AB - The regulation of the cytoplasmic and vacuolar pH values (pHc and pHv) in sycamore (Acer pseudoplatanus L.) cells was analyzed using 31P and 13C nuclear magnetic resonance spectroscopy. Suspension-cultured cells were compressed in the NMR tube and perfused with the help of an original arrangement enabling a tight control of the pH (external pH, pHe) of the carefully oxygenated circulating nutrient medium. Intracellular pH values were measured from the chemical shifts of: CH2-linked carboxyl groups of citric acid below pH 5.7; orthophosphate between pH 5.7 and 8.0; 13C-enriched bicarbonate over pH 8.0. pHc and pHv were independent of pHe over the range 4.5-7.5. In contrast intracellular pH values decreased rapidly below pHe 4.5 and increased progressively at pHe over 7.5. There was an acceleration in the rate of O2 consumption accompanied with a decrease in cytoplasmic ATP concentration as pHe decreased. When the rate of O2 consumption was approaching the uncoupled O2 uptake rate, a loss of pHc control was observed. It is concluded that as pHe decreased, the plasma membrane ATPase consumed more and more ATP to reject the invading H+ ions in order to maintain pHc at a constant value. Below pHe 4.5 the efficiency of the H+ pump to react to back leakage of H+ ions became insufficient, leading to an acidification of pHc and to an alkalinization of pHe. On the other hand, over pHe 7.5 a passive influx of OH- ions was observed, and pHc increased proportionally to the increase of pHe. Simultaneously appreciable amounts of organic acids (malate and citrate) were synthesized by cells during the course of the alkalinization of the cytoplasmic compartment. The synthesis of organic acids which partially counteract the alkalinization of the cytoplasmic compartment may result from a marked activation of the cytoplasmic phosphoenolpyruvate carboxylase induced by an increase in cytoplasmic bicarbonate concentration. The fluctuations of pHv followed a similar course to that of pHc. It is concluded that the vacuole, which represents a potentially large H+ ions reservoir, can counteract H+ (or OH-) ion invasion observed at acidic (or alkaline) pHe contributing to the homeostasis of pHc. PMID- 1629191 TI - Isolation of a carotenoid-containing sub-membrane particle from the chloroplastic envelope outer membrane of pea (Pisum sativum). AB - Chloroplastic envelope membranes isolated from pea (Pisum sativum) leaves are rich in carotenoids, containing approximately 2 micrograms of carotenoid mg-1 protein. We report here that envelopes can be surfactant-solubilized while maintaining association of carotenoids with protein components of the membrane. Treatment of isolated chloroplastic envelope membranes with 0.5% Deriphat 160 (N lauryl-beta-imminodipropionate) causes general solubilization but preserves an envelope sub-membrane fragment which is fractionated by centrifugation in a sucrose gradient and by chromatography on a column of DEAE-Sephacel. The isolated submembrane complex contained five major proteins with M(r) values equivalent to 75,000, 36,000, 34,000 17,500, and 14,500. Spectroscopic and chromatographic analyses revealed that the complex contains violaxanthin and at least one other carotenoid. Carotenoid content of the fractionated complex was estimated as 4.8 micrograms mg-1 protein. Immunoblot analysis reveals that the constituent proteins of this complex are derived from the chloroplastic outer envelope membrane. These data suggest that at least some of the carotenoids of the chloroplastic envelope may be organized by apoproteins. PMID- 1629192 TI - Phosphorylation of casein kinase II by p34cdc2 in vitro and at mitosis. AB - In human epidermal carcinoma A431 cells, the beta subunit of casein kinase II is phosphorylated at an autophosphorylation site and at serine 209 which can be phosphorylated in vitro by p34cdc2 (Litchfield, D. W., Lozeman, F. J., Cicirelli, M. F., Harrylock, M., Ericsson, L. H., Piening, C. J., and Krebs, E. G. (1991) J. Biol. Chem. 266, 20380-20389). Given the importance of p34cdc2 in the regulation of cell cycle events, we were interested in examining the phosphorylation of casein kinase II during different stages of the cell cycle. In this study it is demonstrated that the extent of phosphorylation of serine 209 in the beta subunit is significantly increased relative to phosphorylation of the autophosphorylation site when chicken bursal lymphoma BK3A cells are arrested at mitosis by nocodazole treatment. This result suggests that serine 209 is a likely physiological target for p34cdc2. In addition, the alpha subunit of casein kinase II also undergoes dramatic phosphorylation with an associated alteration in its electrophoretic mobility when BK3A cells or human Jurkat cells are arrested with nocodazole. Phosphopeptide mapping studies indicate that p34cdc2 can phosphorylate in vitro the same peptides on the alpha subunit that are phosphorylated in cells arrested at mitosis. These phosphorylation sites were localized to serine and threonine residues in the carboxyl-terminal domain of alpha. Taken together, the results of this study indicate that casein kinase II is a probable physiological substrate for p34cdc2 and suggest that its functional properties could be affected in a cell cycle-dependent manner. PMID- 1629193 TI - The protein-protein complex between pp60v-src and hsp90 is stabilized by molybdate, vanadate, tungstate, and an endogenous cytosolic metal. AB - In a recent study demonstrating the cell-free reconstitution of the pp60v-src hsp90 complex, we found that the tyrosine kinase-hsp90 complex is stabilized by molybdate (Hutchison, K. A., Brott, B. K., De Leon, J. H., Perdew, G. H., Jove, R., and Pratt, W. B. (1992) J. Biol. Chem. 267, 2902-2908). In this paper, we examine in detail the stabilization of this protein-protein interaction by transition metal oxyanions. The pp60v-src-hsp90 complex is stabilized by sodium molybdate with the same concentration dependence as the glucocorticoid receptor hsp90 complex. As with the steroid receptor heterocomplexes, vanadate and tungstate also stabilize the pp60v-src-hsp90 interaction. Passage of cytosol through a Chelex-100 metal-chelating resin destabilizes the native pp60v-src hsp90 complex, suggesting that the complex is normally stabilized by an endogenous metal factor. Readdition of either the heat-stable components of cytosol or a partially purified endogenous metal factor stabilizes the metal depleted complex. Molybdate also stabilizes the presence of p50, a known hsp90 associated protein, in the pp60v-src heterocomplex. Given the identical effects of transition metal oxyanions on both pp60v-src- and steroid receptor-hsp90 complexes and the lack of any sequence homology between pp60v-src and the receptors, it seems very likely that it is the common component, hsp90, that contains the site of the metal interaction. PMID- 1629194 TI - Cloning and expression of wild-type and mutant forms of the cardiotonic polypeptide anthopleurin B. AB - Venom of the sea anemone Anthopleura xanthogrammica contains a minimum of three polypeptide toxins capable of prolonging the repolarization phase of the action potential. A synthetic gene for the most toxic of the Anthopleura toxins, anthopleurin B (ApB), has been designed, synthesized, and expressed as a fusion protein with the gene 9 product of bacteriophage T7 in Escherichia coli. The fusion protein has been purified and its disulfide bonds reoxidized using glutathione redox couples. Upon cleavage with staphylococcal protease, this protocol yields approximately 1 mg of native ApB/liter of original culture. The recombinant protein has been shown to be identical to natural ApB with respect to amino acid composition, amino-terminal sequence, secondary structure, high pressure liquid chromatographic mobility, and biological activity. A second form of ApB containing additional residues of glycine and arginine at its amino terminus has also been characterized. This protein, termed GR-ApB, is identical in specific activity to the wild-type form. This work lays the groundwork for a detailed analysis of ApB structure and action by site-directed mutagenesis. PMID- 1629195 TI - Two mechanisms of iron uptake from transferrin by melanoma cells. The effect of desferrioxamine and ferric ammonium citrate. AB - The effects of ferric ammonium citrate (FAC) and desferrioxamine (DFO) on iron (Fe), and transferrin (Tf) uptake have been investigated using SK-MEL-28 human melanoma cells, which express the Tf homologue, melanotransferrin, in high concentrations. Previously we demonstrated two separate Fe uptake mechanisms from Tf, viz. a specific process mediated by the transferrin receptor (TfR) and a nonspecific process (Richardson, D. R., and Baker, E. (1990) Biochim. Biophys. Acta 1053, 1-12). Cells exposed to DFO demonstrated up-regulation of the TfR with a concurrent increase in the rate of Fe uptake. Desferrioxamine also stimulated the nonspecific process of Fe uptake, resulting in a further increase in accumulation of Fe over Tf after saturation of the specific TfR. Ferric ammonium citrate had two effects. First, it resulted in down-regulation of the TfR. Second, and paradoxically, it markedly stimulated the rate of Fe uptake from Tf by the nonspecific process without increasing the rate of nonspecific Tf uptake. These data conclusively demonstrate that two entirely different mechanisms of iron uptake from Tf exist in melanoma cells and that ferric ammonium citrate may be a useful experimental tool to further characterize the specific and nonspecific mechanisms of Fe uptake from Tf. PMID- 1629196 TI - The Ser-Arg-Tyr-Asp region of the major surface glycoprotein of Leishmania mimics the Arg-Gly-Asp-Ser cell attachment region of fibronectin. AB - The major surface glycoprotein of Leishmania, gp63, a fibronectin-like molecule, plays a key role in parasite-macrophage interaction. Binding of gp63 to macrophage receptors is inhibited by Arg-Gly-Asp-Ser (RGDS)-containing synthetic peptides of fibronectin and by antibodies to these peptides. However, gp63 lacks an RGDS tetrapeptide. We sought to identify the region of gp63 that antigenically and functionally mimics the RGDS-containing region of fibronectin. We thus synthesized on polyethylene rods overlapping tetracosapeptides covering the whole sequence of Leishmania major gp63. gp63 affinity-purified antibodies raised against fibronectin and against the RGDS-containing fibronectin decapeptide RGDSPASSKP bound specifically to gp63 residues 241-264. Subsequently, by the use of smaller peptides, the gp63 tetrapeptide 252-255 (SRYD) was identified as the minimum antibody binding segment. Single residue substitution peptide analogues showed that indeed Tyr and Gly can be alternatively substituted in the SRYD- and RGDS-containing peptides of gp63 and fibronectin, respectively, without major effects on their antibody binding capacity. Subsequently, we investigated the effect of an SRYD peptide on promastigote-macrophage interaction in vitro; treatment of macrophages with an SRYD-containing gp63 octapeptide efficiently inhibited parasite attachment to macrophage receptors. Thus, the conserved among species sequence SRYD of gp63, with significant hydrophilicity, flexibility, and beta-turn propensity features, mimics antigenically and functionally the RGDS sequence of fibronectin. We suggest that this segment constitutes the putative gp63 adhesion site. PMID- 1629197 TI - cDNA cloning and molecular characterization of MSE55, a novel human serum constituent protein that displays bone marrow stromal/endothelial cell-specific expression. AB - Hemonectin is a lineage-specific cytoadhesive protein that may be involved in the developmentally regulated adhesion of granulocytic cells to bone marrow stroma. Immunoblot analysis using an anti-hemonectin antibody recognizes two distinct immunoreactive species in endothelial cell lysates (approximately M(r) 65,000) and human serum (approximately M(r) 55,000). Initial characterization of the 55 kDa protein has now been completed by isolating the cDNA from a human endothelial cell expression library. Sequence analysis of overlapping clones identifies a composite sequence spanning 2030 nucleotides with an open reading frame of 1173 base pairs. No significant sequence similarity was observed on analysis of current GenBank databases. The open reading frame was expressed as a recombinant protein in Escherichia coli and used as an immunogen for the production of a specific polyclonal antibody. Immunoblotting with this antibody identifies a single immunoreactive species of apparent M(r) 55,000 in HUVEC lysates and human serum, confirming that a secreted form normally circulates as a serum constituent protein. This antibody fails to recognize purified hemonectin, suggesting that the M(r) 55,000 protein is not hemonectin. Cross-species Southern blot analysis reveals persistent hybridizing fragments in all species tested, suggestive of a developmentally conserved function. Northern blot analysis demonstrates expression limited to endothelial and bone marrow stromal cells, but not poly(A) RNA from monkey liver, spleen, brain, lung, and kidney. On this basis, we have designated this novel protein MSE55, for marrow stromal/endothelial cell protein with a molecular mass of 55,000 daltons. Its tissue-specific expression may suggest a functional role in hematopoiesis. PMID- 1629198 TI - Iodophenylarsine oxide and arsenical affinity chromatography: new probes for dithiol proteins. Application to tubulins and to components of the insulin receptor-glucose transporter signal transduction pathway. AB - In our studies of the effects of the trivalent arsenical phenylarsine oxide on insulin-dependent hexose uptake in 3T3-L1 adipocytes, we needed direct methods to study arsenical-protein interactions. In this report, we describe two such new tools. The first is the radiolabeled covalent affinity reagent 4 [125I]iodophenylarsine oxide. This compound has effects on 3T3-L1 adipocytes similar to those of phenylarsine oxide both with respect to effects of hexose uptake and the accumulation of pp15, a phosphotyrosine-containing putative mediator of insulin action. Iodophenylarsine oxide labels numerous proteins in intact cells in a concentration-dependent, but apparently insulin-independent fashion. The second tool is trivalent arsenical affinity chromatography, which we use to show novel direct interactions between trivalent arsenicals and several proteins from 3T3-L1 adipocytes including the insulin-responsive glucose transporter GLUT4, the insulin proreceptor, and both the alpha and beta subunits of tubulin. The non-insulin-dependent glucose transporter GLUT1, the mature insulin receptor, and the fatty acid-binding protein 422(aP2) do not show strong interactions with arsenical resin. These results provide a new chemical approach to the study of both insulin-dependent hexose transport and tubulin function. PMID- 1629199 TI - Identification and characterization of neutral endopeptidase in endothelial cells from venous or arterial origins. AB - Neutral endopeptidase (NEP; enkephalinase, EC 3.4.24.11) is a cell membrane associated zinc metalloprotease, which cleaves peptides like atrial natriuretic peptide (ANP) on the amino side of hydrophobic amino acids. Although NEP is mainly located in reabsorptive epithelia (kidney proximal tubule), it is also present in non-epithelial cells such as neuronal cells. As the renal NEP cannot account for the entire ANP metabolism, other locations were postulated. The present experiments show its expression in endothelial cells (EC) from arterial (bovine pulmonary, porcine, and human aorta) and venous (human umbilical, rabbit ear marginal) origins. Three different methods were used to demonstrate the presence of the protein and its mRNA. 1) NEP enzymatic activity was estimated using both a synthetic ([D-Ala2,Leu5]enkephalin) and a natural substrate (bradykinin). Using the synthetic substrate, the enzymatic activity in EC was completely blocked by thiorphan, a specific NEP inhibitor with an IC50 value in the nanomolar range. In contrast, captopril, bestatin, [2 guanidinoethylmercapto]succinic acid, inhibitors of angiotensin-converting enzyme, aminopeptidases, and carboxypeptidases, respectively, were 10,000 times less active, revealing an inhibition profile similar to that of the purified enzyme. Bradykinin, a natural substrate of NEP, was in part metabolized by NEP, in the presence of captopril, since 50% of the formation of the major metabolite bradykinin 1-7 was inhibited by thiorphan. 2) Immunoreactive NEP was detected on the plasma membrane of rabbit EC using a monoclonal antibody directed against the homologous renal enzyme. 3) NEP mRNA was detected by Northern blot analysis of rabbit EC as a major transcript of 3.9 kilobases. Reverse transcriptase polymerase chain reaction amplification showed the presence of a specific transcript in all EC tested. Therefore, endothelial NEP may play an important role in the inactivation of ANP, bradykinin, and endothelins by its localization facing the circulating vasoactive peptides. PMID- 1629200 TI - Vascular endothelial cell adhesion and spreading promoted by the peptide REDV of the IIICS region of plasma fibronectin is mediated by integrin alpha 4 beta 1. AB - We have recently reported the attachment and spreading of human umbilical vein endothelial cells (HUVECs) upon substrates containing covalently grafted Arg-Glu Asp-Val (REDV) peptide (Hubbell, J. A., Massia, S. P., Desai, N. P., and Drumheller, P. D. (1991) Bio/Technology 9, 568-572). This peptide has been reported to be the minimal active sequence within the CS5 site of the alternatively spliced type III connecting segment (IIICS) region of fibronectin, and the integrin alpha 4 beta 1 has been identified as the receptor on melanoma cells for this site. The integrin alpha 4 beta 1 has also been identified as the receptor for the CS1 site in the IIICS region on cells of neural crest origin, melanoma cells, lymphocytes, and hematopoietic stem cells. In this study, we demonstrate that this integrin also serves as a receptor on HUVECs for the peptide REDV from the CS5 site. The alpha 4 subunit was shown to be expressed upon HUVEC membranes by whole-cell enzyme-linked immunosorbent assay. Antifunctional antibodies directed against integrin subunits alpha 4 and beta 1 inhibited cell adhesion on REDV-grafted substrates, but not on RGD-grafted substrates. The alpha 4 subunit localized into fibrillar structures within spread cells on the REDV-grafted substrates, but not within spread cells on RGD-grafted substrates. Two proteins (144 and 120 kDa) were isolated from HUVEC extracts by REDV ligand affinity chromatography and were demonstrated by immunoprecipitation and Western blot to be the integrin subunits alpha 4 (144 kDa) and beta 1 (120 kDa); furthermore, the immunoprecipitation analyses demonstrated that the subunits formed a complex. HUVEC binding to REDV-grafted substrates was inhibited by both soluble REDV and RGD, demonstrating that adhesion was biospecific and that the REDV peptide is RGD-like. In this report we demonstrate for the first time that alpha 4 is present in the endothelial cell membrane, in contrast to previous reports by others, and that integrin alpha 4 beta 1 is the receptor for REDV-mediated adhesion to the IIICS region of region of plasma fibronectin. PMID- 1629201 TI - Exolytic hydrolysis of toxic plant glucosides by guinea pig liver cytosolic beta glucosidase. AB - We demonstrate that although the guinea pig liver cytosolic beta-glucosidase does not catalyze the hydrolysis of gentiobiose, it does hydrolyze, disaccharide containing glycosides such as p-nitrophenyl-beta-D-gentiobioside (Glc beta 1--- 6Glc beta-pNP) and mandelonitrile-beta-D-gentiobioside (amygdalin). Furthermore, we establish that the enzyme attacks disaccharide glycosides exolytically; specifically, we document the exolytic deglucosylation of amygdalin and the generation of the intermediate monosaccharide glycoside mandelonitrile-beta-D glucoside prior to the formation of the aglycone (mandelonitrile). We also show that the cytosolic beta-glucosidase catalyzes the hydrolysis of various phenolic (e.g. arbutin and salicin) and cyanogenic plant glucosides (e.g. prunasin). Using the everted gut-sack technique, we demonstrate that the plant glucosides, amygdalin, prunasin, and vicine, are transported across the small intestine of the guinea pig efficiently and without being hydrolyzed. Based on these data we speculate that the cytosolic beta-glucosidase may participate in biotransformation of toxic plant glucosides. PMID- 1629202 TI - Insect lipid transfer particle can facilitate net vectorial lipid transfer via a carrier-mediated mechanism. AB - The mechanism of facilitated lipid transfer by insect or mammalian plasma lipid transfer proteins has not been elucidated. Transfer catalysts may act as carriers of lipid between donor and acceptor lipoproteins or, alternatively, transfer may require formation of a ternary complex. This study was designed to determine if Manduca sexta hemolymph lipid transfer particle (LTP) can facilitate net vectorial transfer of lipid without concomitant contact between donor and acceptor lipoproteins and LTP. M. sexta [3H]diacylglycerol-high density lipophorin-larval ([3H]DAG-HDLp-L) and human low density lipoprotein (LDL) were covalently bound to Sepharose matrices and packed into separate columns. In incubations lacking LTP, greater than 98% of the recovered DAG remained associated with HDLp-L. An unrelated hemolymph storage protein, arylphorin, was unable to catalyze the transfer of DAG between solid-phase lipoproteins. Facilitated transfer of DAG from HDLp-L to LDL was observed when LTP was circulated between the columns. Under these conditions, facilitated transfer occurred at a rate of 2.24 ng of DAG/h (versus 0.16 microgram of DAG/h in the control), and after 16 h greater than 26% of recovered labeled DAG was transferred to LDL. This corresponds to a 14-fold rate enhancement induced by LTP. The LTP-specific transfer of DAG between physically separated lipoproteins demonstrates the ability of LTP to facilitate net lipid transfer via a carrier mediated mechanism in the absence of a ternary complex involving donor, acceptor, and catalyst. In experiments aimed at assessing the relative contribution of ternary complex formation to DAG transfer, acceptor LDL was circulated with HDLp L remaining immobilized. Under these conditions, LTP induced a 13-fold rate enhancement from 1.3 to 16.3 micrograms of DAG/h. The similar rate enhancements observed with both lipoproteins bound and only donor bound suggest the overall contribution of ternary complex formation to facilitated lipid transfer is insignificant. The described system should prove useful in mechanistic studies of other transfer proteins as well as studies of transfer of other lipids. PMID- 1629203 TI - Interaction between G-actin and myosin subfragment-1 probed by covalent cross linking. AB - The topography of rapid equilibrium complexes formed between G-actin and myosin subfragment-1, which are the first kinetic intermediates in the polymerization process into F-acto-S1 filaments, has been probed by chemical cross-linking. In the absence of ATP, cross-linking of G-actin-S1 complexes by 1-ethyl-3-(3 dimethylaminopropyl)-carbodiimide (EDC) yielded a major 165-170-kDa and a fainter 200-205-kDa doublet polypeptide. The actin:S1 molar ratio was 1 in the EDC-cross linked complexes, using either double labeling techniques or the method combining EDC + N-hydroxysuccinimide. Chemical cleavages of the covalently cross-linked complexes by formic acid and N-hydroxylamine (Sutoh, K. (1983) Biochemistry 22, 1579-1585) showed that in the main cross-linked 165-kDa polypeptide, the 1-12 acidic N-terminal region of actin was covalently linked to the lysine-rich region connecting the central 50-kDa domain to the C-terminal 20-kDa domain of S1, as in F-acto-S1 complexes. G-actin, but not F-actin, was covalently cross-linked to S1 by N,N'-paraphenylenedimaleimide (p-PDM). A major 195-kDa and a minor 165-kDa polypeptide were obtained, could be separated from actin and S1 by DEAE-cellulose chromatography, and did not exhibit actin-activated Mg-ATPase activity. Both EDC cross-linked and p-PDM-cross-linked complexes between G-actin and S1 could be incorporated into F-acto-S1 decorated filaments. The C-terminal cysteine 374 of actin is involved in the p-PDM cross-linked 195-kDa complex. Accordingly, a covalent photocross-linked 200-kDa conjugate was formed between S1 heavy chain and benzophenone-G-actin, obtained by covalent modification of Cys374 by benzophenonemaleimide (Tao, T., Lamkin, M., and Scheiner, C. J. (1985) Arch. Biochem. Biophys. 240, 627-634). These results demonstrate that (i) G-actin-S1 and F-actin-S1 complexes display a large similarity in the EDC-cross-linked electrostatic close contacts and (ii) a change in the environment of Cys374 is linked to the polymerization into F-actin-S1 decorated filaments. PMID- 1629204 TI - Monovalent cation selectivity for ATP-dependent association of the glucocorticoid receptor with hsp70 and hsp90. AB - We have reported previously that incubation of the immunopurified transformed hormone-free glucocorticoid receptor with rabbit reticulocyte lysate reconstitutes the receptor complex with hsp90 and that reconstitution is accompanied by concomitant repression of DNA binding activity and regeneration of the steroid binding conformation (Scherrer, L. C., Dalman, F. C., Massa, E., Meshinchi, S., and Pratt, W. B. (1990) J. Biol. Chem. 265, 21397-21400). In this work we further characterize this system by defining the small M(r) components of reticulocyte lysate required for both structural and functional reconstitution of the receptor-hsp90 complex. Reconstitution is ATP-dependent and there is a direct relationship between the extent of hsp90 binding to the receptor and the number of specific steroid binding sites that are generated. Dialysis of reticulocyte lysate inactivates its reconstituting activity. Addition of an ATP-regenerating system or readdition of small M(r) lysate components (in the form of a Centricon C30 filtrate) has little effect, but the presence of both restores full reconstituting activity to dialyzed lysate, as assayed by steroid binding activity and by the binding of hsp90 and hsp70 to the receptor. The small M(r) activity is heat-stable, and it can be completely replaced by NH+4, K+, and Rb+, with K+ producing a maximal effect at the concentration normally present in undialyzed lysate. Na+ and Li+ have no reconstituting activity. This ion selectivity demonstrates that a monovalent cation binding site is involved in receptor heterocomplex reconstitution. It is intriguing that the protein unfoldase (e.g. clathrin uncoating ATPase) activity of hsp70 is known to have a similar monovalent cation dependence, and that under all conditions where hsp90 becomes bound to the receptor, we find that hsp70 is also bound. PMID- 1629205 TI - Activation of a Gi protein in mouse sperm membranes by solubilized proteins of the zona pellucida, the egg's extracellular matrix. AB - Zona pellucida (ZP)-induced acrosomal exocytosis in mammalian spermatozoa is thought to be mediated by signal transduction cascades similar to those found in hormonally responsive cells. In order to characterize this process further, we have examined the role of GTP-binding regulatory proteins (G proteins) in coupling sperm-ZP interaction to intracellular second messenger systems in mouse sperm. An in vitro signal transduction assay was developed to assess ZP-G protein dynamics in sperm membrane preparations. Guanosine 5'-3-O-(thio)triphosphate (GTP gamma S), a poorly hydrolyzable analogue of GTP, bound to these membranes in a specific and concentration-dependent fashion which reached saturation at 100 nM. Incubation of the membrane preparations with heat-solubilized ZP resulted in a significant increase in specific GTP gamma S binding in a concentration-dependent fashion with a half-maximal response at 1.25-2 ZP/microliters. Solubilized ZP also caused a significant increase in high affinity GTPase activity in the membranes over basal levels. Mastoparan increased specific GTP gamma S binding to the sperm membranes and stimulated high-affinity membrane GTPase activity to levels consistently greater than that seen with the solubilized ZP. Mastoparan, together with solubilized ZP, gave the same level of stimulation of GTP gamma S binding as mastoparan alone. Pertussis toxin completely inhibited the ZP stimulated GTP gamma S binding, but only decreased mastoparan-stimulated GTP gamma S binding by 70-80%. Purified ZP3, the ZP component which possesses quantitatively all of the acrosomal exocytosis-inducing activity of the intact ZP, stimulated GTP gamma S binding to the same level as solubilized ZP; ZP1 and ZP2 did not stimulate GTP gamma S binding. ZP from fertilized eggs (ZPf), which does not possess acrosome reaction-inducing activity, also failed to stimulate GTP gamma S binding to sperm membranes. These data demonstrate the direct activation of a Gi protein in sperm membrane preparations in response to the ZP glycoprotein, ZP3, that induces the acrosome reaction. These data imply that Gi protein activation is an early event in the signal sequence leading to sperm acrosomal exocytosis. PMID- 1629206 TI - Pulsatile Ca2+ extrusion from single pancreatic acinar cells during receptor activated cytosolic Ca2+ spiking. AB - Ca2+ extrusion was measured simultaneously with the free intracellular Ca2+ concentration ([Ca2+]i) from single pancreatic acinar cells placed in microdroplets of extracellular solution (Tepikin, A. V., Voronina, S. G., Gallacher, D. V., and Petersen, O. H. (1992) J. Biol. Chem. 267, 3569-3572). Submaximal stimulation with cholecystokinin usually evoked discrete cytosolic Ca2+ spikes and each of these spikes was associated with a discrete and virtually synchronous pulse of Ca2+ extrusion into the extracellular microdroplet solution. When ACh evoked repetitive discrete [Ca2+]i spikes, each spike was also accompanied by a discrete pulse of Ca2+ extrusion. The velocity of Ca2+ extrusion oscillated with a time course similar to that of [Ca2+]i. The extracellular solution in our experiments had a low total calcium concentration (15-35 microM) and only a limited number of [Ca2+]i spikes (2-8) could be evoked. The magnitudes of the [Ca2+]i spikes and the amounts of Ca2+ extruded during each spike gradually decreased in each experiment. During the first cholecystokinin-evoked cytosolic Ca2+ spike the Ca2+ extrusion corresponded to a loss of 15-70% (mean value 39% +/- 12) of the mobilizable cellular calcium pool. The substantial pulsatile Ca2+ extrusion occurring synchronously with the receptor-activated cytosolic Ca2+ spikes is therefore an important element in repetitively bringing back [Ca2+]i to the resting level. PMID- 1629207 TI - Evidence that a salt bridge in the light chain contributes to the physical stability difference between heavy and light human ferritins. AB - Human ferritin, a multimeric iron storage protein, is composed by various proportions of two subunit types: the H- and L-chains. The biological functions of these two genic products have not been clarified, although differences in reactivity with iron have been shown. Starting from the hypothesis that the high stability typical of ferritin is an important property which may be relevant for its iron storage function, we studied ferritin homopolymers of H- and L-chains in different denaturing conditions. In addition we analyzed 13 H-chain variants with alterations in regions conserved within mammalian H-chains. In all the denaturation experiments H-chain ferritin showed lower stability than L-chain ferritin. The difference was greater in guanidine HCl denaturation experiments, where the end products are fully unfolded peptides, than in acidic denaturation experiments, where the end products are peptides with properties analogous to "molten globule." The study on H-chain variants showed: (i) ferritin stability was not affected by alterations of regions exposed to the inner or outer surface of the shell and not involved in intra- or inter-chain interactions; (ii) stability was reduced by alterations of sequences involved in inter-subunit interactions such as the deletion of the N-terminal extension or substitutions along the hydrophobic and hydrophilic channels; (iii) stability was increased by the substitution of 2 amino acids inside the four-helix bundle with those of the homologous L-chain. One of the residues is involved in a salt bridge in the L chain, and we concluded that the stability difference between H- and L-ferritins is to a large extent due to the stabilizing effect of this salt bridge on the L subunit fold. PMID- 1629208 TI - Effect of temperature on the creatine kinase equilibrium. AB - The effect of temperature on the apparent equilibrium constant of creatine kinase (ATP:creatine N-phosphotransferase (EC 2.7.3.2)) was determined. At equilibrium the apparent K' for the biochemical reaction was defined as [formula: see text] The symbol sigma denotes the sum of all the ionic and metal complex species of the reactant components in M. The K' at pH 7.0, 1.0 mM free Mg2+, and ionic strength of 0.25 M at experimental conditions was 177 +/- 7.0, 217 +/- 11, 255 +/ 10, and 307 +/- 13 (n = 8) at 38, 25, 15, and 5 degrees C, respectively. The standard apparent enthalpy or heat of the reaction at the specified conditions (delta H' degree) was calculated from a van't Hoff plot of log10K' versus 1/T, and found to be -11.93 kJ mol-1 (-2852 cal mol-1) in the direction of ATP formation. The corresponding standard apparent entropy of the reaction (delta S' degree) was +4.70 J K-1 mol-1. The linear function (r2 = 0.99) between log10 K' and 1/K demonstrates that both delta H' degree and delta S' degree are independent of temperature for the creatine kinase reaction, and that delta Cp' degree, the standard apparent heat capacity of products minus reactants in their standard states, is negligible between 5 and 38 degrees C. We further show from our data that the sign and magnitude of the standard apparent Gibbs energy (delta G' degree) of the creatine kinase reaction was comprised mostly of the enthalpy of the reaction, with 11% coming from the entropy T delta S' degree term. The thermodynamic quantities for the following two reference reactions of creatine kinase were also determined. [formula: see text] The delta H degree for Reaction 2 was -16.73 kJ mol-1 (-3998 cal mol-1) and for Reaction 3 was -23.23 kJ mol-1 ( 5552 cal mol-1) over the temperature range 5-38 degrees C. The corresponding delta S degree values for the reactions were +110.43 and +83.49 J K-1 mol-1, respectively. Using the delta H' degree of -11.93 kJ mol-1, and one K' value at one temperature, a second K' at a second temperature can be calculated, thus permitting bioenergetic investigations of organs and tissues using the creatine kinase equilibria over the entire physiological temperature range. PMID- 1629209 TI - O-glycosylation of the coronavirus M protein. Differential localization of sialyltransferases in N- and O-linked glycosylation. AB - It has previously been shown that the M (E1) glycoprotein of mouse hepatitis virus strain A59 (MHV-A59) contains only O-linked oligosaccharides and localizes to the Golgi region when expressed independently. A detailed pulse-chase analysis was made of the addition of O-linked sugars to the M protein; upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis, three different electrophoretic forms could be distinguished that corresponded to the sequential acquisition of N acetylgalactosamine (GalNAc), galactose (Gal), and sialic acid (SA). A fourth and fifth form could also be detected which we were unable to identify. Following Brefeldin A treatment, the M protein still acquired GalNAc, Gal, and SA, but the fourth and fifth forms were absent, suggesting that these modifications occur in the trans-Golgi network (TGN). In contrast, in the presence of BFA, the G protein of vesicular stomatitis virus (VSV), which contains N-linked oligosaccharides, acquired Gal and fucose but not SA. These results are consistent with earlier published data showing that Golgi compartments proximal to the TGN, but not the TGN itself, relocate to the endoplasmatic reticulum/intermediate compartment. More importantly, our data argue that, whereas addition of SA to N-linked sugars occurs in the TGN the acquisition of both SA on O-linked sugars and the addition of fucose to N-linked oligosaccharides must occur in Golgi compartments proximal to the TGN. The glycosylation of the M protein moreover indicates that it is transported to trans-Golgi and TGN. This was confirmed by electron microscopy immunocytochemistry, showing that the protein is targeted to cisternae on the trans side of the Golgi and co-localizes, at least in part, with TGN 38, a marker of the TGN, as well as with a lectin specific for sialic acid. PMID- 1629210 TI - Structure-function relationships in an antifreeze polypeptide. The role of neutral, polar amino acids. AB - An alanine-rich, alpha-helical antifreeze polypeptide (AFP) from the winter flounder and seven analogs with variations in the arrangement of neutral, polar amino acids were synthesized. Circular dichroism studies determined that all of the peptides, except for one containing a proline residue, were essentially 100% alpha-helical. Freezing point depression data, analyzed by three methods, showed that rearrangement of polar residues resulted in moderate to complete loss of anti-freeze activity. It was observed that ice crystals grow as hexagonal bipyramids in dilute solutions, with a constant c to alpha axis ratio of about 3.3. Above a critical threshold concentration, which may depend on the AFP to ice binding constant and reflect the onset of cooperative interactions, growth ceases until the temperature is lowered to the freezing point. We conclude that a specific arrangement of both threonine and asparagine (or aspartic acid) residues is critical for maximal activity and that the AFPs probably bind to the pyramidal faces of ice with a specific orientation. These conclusions are consistent with a recent report (Knight, C. A., Cheng, C. C., and DeVries, A. L. (1991) Biophys. J. 59, 409-418) that a similar AFP adsorbs to the [2021] pyramidal planes of ice in dilute solution. PMID- 1629211 TI - Coagulation factor X activating enzyme from Russell's viper venom (RVV-X). A novel metalloproteinase with disintegrin (platelet aggregation inhibitor)-like and C-type lectin-like domains. AB - We determined the complete amino acid sequence of RVV-X, the blood coagulation factor X activating enzyme, isolated from Russell's viper venom and studied structure-function relationships. RVV-X (M(r) 79,000) consists of a disulfide bonded two-chain glycoprotein with a heavy chain of M(r) 59,000 and a light chain of heterogeneous M(r) 18,000 (LC1) and 21,000 (LC2). These chains were separated after reduction and S-pyridylethylation, and the isolated major component LC1 was used for sequence analysis. The heavy chain consists of 427 residues containing four asparagine-linked oligosaccharides, and its entire sequence was similar to that of the high molecular mass hemorrhagic protein, HR1B, isolated from the venom of Trimere-surus flavoviridis. The heavy chain contains three distinct domains, metalloproteinase, disintegrin (platelet aggregation inhibitor)-like and unknown cysteine-rich domains. On the other hand, light chain LC1 consists of 123 amino acid residues containing one asparagine-linked oligosaccharide and shows sequence homology similar to that found in the so-called C-type (Ca(2+) dependent) lectins. Therefore, RVV-X is a novel metalloproteinase containing a mosaic structure with distintegrin-like, cysteine-rich, and C-type lectin-like domains. RVV-X potently inhibits collagen- and ADP-stimulated platelet aggregations, probably via its distintegrin-like domain, although this domain does not contain the Arg-Gly-Asp sequence which is conserved in various venom distintegrins and which is thought to be one of the interaction sites for platelet integrins. Our findings also indicate that snake venom factor IX/factor X-binding protein with a C-type lectin structure (Atoda, H., Hyuga, M., and Morita, T. (1991) J. Biol. Chem. 266, 14903-14911) inhibits RVV-X-catalyzed factor X activation; hence, the light chain of RVV-X probably participates in recognizing some portion of the zymogen factor X. PMID- 1629212 TI - The all-D-configuration segment containing the IKVAV sequence of laminin A chain has similar activities to the all-L-peptide in vitro and in vivo. AB - Laminin is a basement membrane glycoprotein that has diverse biological activities. A sequence on the A chain containing IKVAV (Ile-Lys-Val-Ala-Val) has been shown to promote neurite outgrowth, cell adhesion, and tumor growth and metastasis. Here we have determined the structural requirements of this synthetic peptide for biological activity. Twelve-amino acid-long all-L- (LAM-L) and all-D peptide (LAM-D) segments as well as an alternating D- and L-amino acid-containing peptide (LAM-DL), which included the IKVAV sequence (residues 2097-2108), were synthesized. Circular dichroism spectral analysis revealed a mirror image conformation of LAM-D and LAM-L with mainly beta-sheet and to a minor extent alpha-helical structure. LAM-DL did not exhibit any significant ordered conformational features. LAM-D and LAM-L showed similar cell attachment activities for rat pheochromocytoma cells (PC12), whereas LAM-DL was inactive. A peptide analog with randomized IKVAV sequence (LAM-RM) was also inactive. A similar trend was observed in competition experiments of the four peptides with laminin in analogous cell attachment assays. In in vivo experiments, both LAM-D and LAM-L were capable of increasing tumor growth when subcutaneously injected into mice with murine melanoma cells B16F10. Results indicate that the conformational status of the IKVAV domain is a contributing factor in determining the biological activity but that there is no strict requirement for a specific chirality. There is a likely sequence specificity to the IKVAV region. PMID- 1629213 TI - Upstream sequence elements required for NarL-mediated activation of transcription from the narGHJI promoter of Escherichia coli. AB - Transcription of the narGHJI operon (encoding nitrate reductase) in Escherichia coli is primarily dependent on the activation of the pleiotropic transacting factor Fnr, which interacts with the promoter through a cis element (Fnr box) located near the transcription start site. Further stimulation of transcription occurs in the presence of nitrate and is dependent on activation of the transacting factor NarL and a cis-acting sequence (NarL box) located approximately 200 base pairs upstream from the transcription start site. To define the structure of the NarL box, alterations in the NarL box region, generated by saturation mutagenesis of the sequence from positions -184 to -202 in the narGHJI promoter of a narG::lacZ fusion-bearing plasmid, were analyzed for their effects on NarL-mediated stimulation of transcription. Single base substitutions that significantly reduced the NarL-mediated stimulation were restricted to a 6-base sequence, TACTCC, located at positions -193 to -198 in the narGHJI promoter. When 2 bases were modified, NarL-mediated stimulation was severely reduced when one or both alterations were located within the 6-base sequence. Attempts to restore NarL-mediated stimulation with an inverted NarL box were not successful. Although previous studies suggested that NarL-mediated stimulation of transcription may occur by a DNA looping mechanism, the results presented here demonstrate that it does not involve the passive formation of a simple DNA loop. Replacement of 94 or 108 bases of the approximately 150 base sequence between the Fnr box and the NarL box with an unrelated sequence resulted in elimination of NarL-mediated stimulation of transcription. Furthermore, shifting of most of the intervening sequence or defined segments of the sequence by 4 bases while maintaining the position of the NarL box relative to sequences required for Fnr-dependent, anaerobic transcription also eliminated the NarL mediated stimulation. We conclude that in addition to the 6-base NarL box located on a specific face of the promoter DNA, the stimulation of transcription by NarL requires some specific sequences and/or higher order structure specified by the DNA that separates the NarL box from the Fnr box. PMID- 1629214 TI - Quantitative analysis of SH2 domain binding. Evidence for specificity and competition. AB - We report the development of a quantitative assay for measuring SH2 domain binding in vitro. Using this assay we have analyzed the binding of purified recombinant SH2 domains from ras GTPase activating protein (GAP) and the 85-kDa subunit of phosphatidylinositol 3-kinase (p85) to proteins from epidermal growth factor-stimulated and v-src-transformed cells. The purified recombinant SH2 domains from GAP and p85 bind to the tyrosine phosphorylated epidermal growth factor receptor with nanomolar affinities. Moreover, competition studies suggest that these two proteins bind to equivalent or overlapping sites on this receptor. In v-src-transformed cells the purified recombinant SH2 domains from GAP and p85 bind to distinct but overlapping sets of proteins. PMID- 1629215 TI - Processive proofreading is intrinsic to T4 DNA polymerase. AB - DNA replication occurs in vivo with very high processivity, meaning that the replication complex assembles at the origin(s) of replication and then performs template-directed synthesis of DNA over virtually the entire genome without dissociation. Such processivity also characterizes reconstituted replication holoenzyme complexes in vitro. However, the isolated DNA polymerases are much less processive, especially under physiological conditions. In this paper we monitor the degree of processivity displayed by the bacteriophage T4-coded DNA polymerase while in its proofreading mode by asking whether an isolated polymerase can "edit-out" the 3'-terminal nucleotide from the primer (using the 3'----5'-exonuclease activity of the polymerase) and then switch into the synthesis mode without dissociating from the DNA template. This "switch experiment" is accomplished by using mismatched primer/template substrates as an experimental tool to mimic the situation that T4 DNA polymerase encounters after a misincorporation event has occurred. By performing experiments under single turnover conditions (obtained using a heparin trap), we demonstrate that T4 DNA polymerase, upon encountering a misincorporated base, neither synthesizes the next base nor dissociates into solution. Instead, with a greater than 80% probability, it removes the misincorporated base and then continues synthesis in a fully processive manner. We also show that the removal of a doubly mispaired sequence from the 3'-terminus of the primer, followed by synthesis, is comparably processive. In contrast, the apparent processivity of removing a triply mispaired terminus is much reduced. Taken together, these observations are consistent with the notion that the "editing active site" of the T4 enzyme optimally accommodates only two unpaired nucleotide residues. Our results do not support the idea that the exonuclease activity of T4 DNA polymerase is highly selective for mismatched termini; they suggest instead that the dwell time at a misincorporated base determines overall editing efficiency. The integrated results of this study provide additional insight into the structure of the T4 DNA polymerase, as well as into the interactions between the polymerase and the polymerase accessory proteins that are required to provide the holoenzyme complex with full processivity. PMID- 1629216 TI - Biochemical and biophysical characterization of human recombinant IgE-binding protein, an S-type animal lectin. AB - IgE-binding protein (epsilon BP) was originally identified by virtue of its affinity for IgE. It is now known to be a beta-galactoside-binding lectin with the characteristic of an S-type carbohydrate recognition domain. The protein is composed of two domains: the amino-terminal domain consisting of tandem repeats and the carboxyl-terminal domain containing sequences shared by other S-type carbohydrate recognition domains. The amino-terminal domain also contains a number of potential recognition sites for collagenase cleavage. In this study, human epsilon BP was first expressed in Escherichia coli, and the carboxyl terminal domain (epsilon BP-C) was then generated by collagenase digestion of epsilon BP. By equilibrium dialysis, the association constants of epsilon BP and epsilon BP-C for lactose were found to be similar (6.0 +/- 0.70) x 10(4) M-1 and (4.7 +/- 0.27) x 10(4) M-1, respectively. Both polypeptides contain only one lactose-binding site/molecule. By an assay involving binding of 125I-labeled epsilon BP or epsilon BP-C to solid phase IgE, and inhibition of this binding by saccharides, it was determined that epsilon BP-C retains the saccharide specificity of epsilon BP. Importantly, although unlabeled epsilon BP-C inhibited the binding of the radiolabeled epsilon BP to IgE, unlabeled epsilon BP caused increased binding to IgE, suggesting self-association among epsilon BP molecules. Oligomeric structures resulting from self-association of epsilon BP were confirmed by chemical cross-linking studies. Furthermore, epsilon BP possesses hemagglutination activity on rabbit erythrocytes, whereas epsilon BP-C lacks such activity. Based on these results, we propose a structural model for multivalency of epsilon BP: dimerization or oligomerization of epsilon BP occurs through intermolecular interaction involving the amino-terminal domain. PMID- 1629217 TI - Induction of interleukin 1 beta expression from human peripheral blood monocyte derived macrophages by 9-hydroxyoctadecadienoic acid. AB - Oxidatively modified low density lipoproteins (LDL) have recently been proposed to play a role in atherogenesis by promoting foam cell formation and endothelial cell toxicity. The purpose of the present study was to determine whether modified LDL could also induce macrophage release of interleukin 1 beta (IL-1 beta), a cytokine which enhances vascular smooth muscle cell proliferation, another feature of the atherosclerotic process. LDL were oxidatively modified by incubation with either Cu2+ (Cu(2+)-LDL) or human peripheral blood monocyte derived macrophages (M-LDL). Incubation of these modified LDL with macrophages (6 x 10(6) cells/culture) resulted in a dose-dependent induction of IL-1 beta release. At 300 micrograms protein/ml, Cu(2+)-LDL and M-LDL induced 422 and 333 pg of IL-1 beta/culture, respectively. Saponified Cu(2+)-LDL and M-LDL were shown to contain 9- and 13-hydroxyoctadecadienoic acid (HODE), lipid oxidation products of linoleate. When tested for activity in macrophage culture (3 x 10(6) cells/culture), it was found that 9-HODE and 13-HODE (final concentration 33 microM) induced the release of 122 and 43 pg of IL-1 beta/culture, respectively, whereas untreated cells released only 4 pg of IL-1 beta/culture. Incubation of macrophages with cholesteryl-9-HODE also induced IL-1 beta release; however, the degree of induction of IL-1 beta release by 9-HODE or its cholesteryl ester relative to modified LDL suggests that other components in oxidized LDL may also contribute to IL-1 beta induction. 9-HODE was rapidly taken up by macrophages, and the kinetics were similar to IL-1 beta release. A 1.5- to 6-fold increase in the level of IL-1 beta mRNA was detected as little as 3-h post-9-HODE treatment. The induction of IL-1 beta release from human monocyte-derived macrophages by 9 HODE and cholesteryl-9-HODE suggests a role for modified LDL, and its associated linoleate oxidation products, in vascular smooth muscle cell proliferation. PMID- 1629218 TI - Cytochrome P-450terp. Isolation and purification of the protein and cloning and sequencing of its operon. AB - Cytochromes P-450 are extremely important in the oxidative metabolism of a variety of endogenous and exogenous compounds in pro- and eukaryotic organisms. Progress in understanding the structure and mechanism of action of this superfamily of enzymes has been hampered by the properties of the eukaryotic enzymes and the availability of only one well-characterized prokaryotic enzyme as a model. We report here the isolation of a Pseudomonas species which will utilize a monoterpene natural product, alpha-terpineol, as its sole source of carbon and energy. Approximately 1% of the soluble protein in the cell-free extract is a novel cytochrome P-450 (P-450terp). This enzyme and its associated iron sulfur protein electron carrier (terpredoxin) have been purified to homogeneity and their NH2-terminal amino acid sequences determined. The amino acid sequences of six tryptic peptide fragments of cytochrome P-450terp have also been determined. This sequence information was used to clone the gene encoding cytochrome P 450terp. Three clones representing approximately 8 kilobase pairs of unique sequences were selected and sequenced. Five non-overlapping open reading frames (ORFs) were found in the sequences, and the translated sequences were used to search the Protein Identification Resource for comparable proteins. The ORFs were identified as: 1) an alcohol dehydrogenase, 2) an aldehyde dehydrogenase, 3) cytochrome P-450terp, 4) terpredoxin reductase, and 5) terpredoxin. The identification of both the cytochrome P-450terp and terpredoxin DNA sequence was confirmed by the presence of each of the corresponding amino acid sequences found in the purified proteins. The five ORFs were bounded on both the 5' and 3' ends by consensus factor-independent terminator sequences. A consensus promoter sequence was found immediately 5' to the first ORF. These results indicate that we have sequenced the complete terp operon. Comparison of the amino acid sequence of cytochrome P-450terp to that of all other cytochromes P-450 has shown that it is the first member of the gene family CYP108. Preliminary characterization of the chemical and physical properties and the preparation of crystals of this new cytochrome P-450, suitable for x-ray diffraction analysis, indicate that it will be useful in comparison studies with other members of this class of proteins. PMID- 1629220 TI - Acetylcholinesterase. Two types of modifications confer resistance to insecticide. AB - Quantitative and qualitative changes in acetylcholinesterase confer resistance to insecticides. We have constructed several Drosophila melanogaster strains producing various amounts of enzyme by P-mediated transformation. Toxicological analysis of these strains demonstrates that resistance to organophosphorus insecticides is correlated with the amount of acetylcholinesterase in the central nervous system. Resistance may also be qualitatively determined. Comparison of the Drosophila acetylcholinesterase gene between a resistant strain caught in the wild and a wild type susceptible strain only revealed one nucleotide transition resulting in the replacement of a phenylalanine by a tyrosine. Flies mutant for acetylcholinesterase and rescued with a minigene mutagenized for this same transition produced an altered enzyme which renders flies resistant to pesticides. PMID- 1629219 TI - Bovine bone activin enhances bone morphogenetic protein-induced ectopic bone formation. AB - A 25-kDa homodimeric protein was purified from demineralized bovine bone extract and identified as activin A. The bovine bone activin enhanced formation of ectopic bone in rat subcutis when implanted in combination with partially purified bovine bone morphogenetic protein (BMP-2, BMP-3) in collagen/ceramic carrier. The implants, removed at 14 days, contained markedly elevated levels of alkaline phosphatase activity. Histological examination revealed an extensive formation of woven bone with very little cartilage. In contrast, a combination of transforming growth factor-beta 2 and BMP promoted formation of bone with an abundance of cartilage. The implants with BMP alone exhibited some osteoinductive activity, while the implants with activin alone showed no activity. These results demonstrate that bone is a rich source of activin and that activin plays an important role in modulating bone formation. PMID- 1629221 TI - Proteoglycans from the swarm rat chondrosarcoma. Structure of the aggregates extracted with associative and dissociative solvents as revealed by electron microscopy. AB - Proteoglycan aggregates were extracted from Swarm rat chondrosarcoma tissue in the native state and compared with proteoglycan aggregates isolated dissociatively with 4 M guanidine HCl. Purified aggregates were examined with a variety of electron microscopic techniques. In some cases they showed a structure of the central filament identical to that of the link-stabilized central filament observed in earlier experiments where the separated constituents were allowed to reconstitute (Morgelin, M., Paulsson, M., Hardingham, T. E., Heinegard, D., and Engel, J. (1988) Biochem. J. 253, 175-185). The tight packing of proteoglycan monomers along the hyaluronate with a minimum distance of 12 nm between adjacent E1 strands also could thus be confirmed for never dissociated aggregates. The results therefore show that the organization of proteoglycan aggregates assembled in vitro from the participating molecules is representative for conditions in situ. An additional structural type of central filament was observed in the preparations. This contained long stretches of free hyaluronate interspaced by short stretches of central filament with condensed arrays of link protein proteoglycan. Chemical cross-linking in combination with low shear electron microscopical techniques showed that this discontinuous central filament structure is not an artifact of specimen preparation. The addition of suprastoichiometric amounts of exogenous link protein did not affect the central filament structure with the low packing density. Densely and loosely packed types of central filament were isolated in varying relative amounts with different associative and dissociative solvents. PMID- 1629222 TI - Activation of human furin precursor processing endoprotease occurs by an intramolecular autoproteolytic cleavage. AB - Human furin is a calcium-dependent serine endoprotease that can efficiently cleave many precursor proteins on the carboxyl side of the consensus cleavage sequence, -Arg-X-Lys/Arg-Arg-, both in vivo and in vitro. Analysis of furin proteins in extracts of cells infected with a vaccinia recombinant expressing human furin show that the enzyme is present as two prominent forms of 90 and 96 kDa. Because the structurally related bacterial subtilisins require endoproteolytic removal of the NH2-terminal pro-region by an autocatalytic intramolecular cleavage, we speculated that the size heterogeneity in the furin doublet similarly may result from a proteolytic removal of an NH2-terminal pro region. Here we report identification of the 90-kDa furin NH2 terminus and, based on the reported sequence of the furin cDNA, demonstrate that this furin protein is derived from a larger precursor by an endoproteolytic cleavage on the COOH terminal side of a consensus furin cleavage site, -Arg-Thr-Lys-Arg107-. Expression of mutant furin molecules containing an altered cleavage site (Arg104- --Ala or Arg107----Gly) resulted in the production of only the 96-kDa furin protein. Assays of furin-dependent cleavage of a protein substrate in vitro showed that proteolytic activity was associated with the 90-kDa and not the 96 kDa furin protein, demonstrating that removal of the NH2-terminal pro-region is required for furin activity. Expression of a third furin construct containing a mutation of the active site aspartate (Asp153----Asn) similarly resulted in the expression of only the 96-kDa protein, suggesting that furin activation occurs by an autoproteolytic cleavage. Finally, the production of 90-kDa furin from either site-directed furin mutant could not be potentiated by overexpressing active furin, suggesting that the autoproteolytic activation was an intramolecular event. PMID- 1629223 TI - Precursor for the light-harvesting chlorophyll a/b-binding protein synthesized in Escherichia coli blocks import of the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase. AB - When synthesized in Escherichia coli, the light-harvesting chlorophyll a/b binding protein (LHCP) precursor accumulates in inclusion-like bodies (Abad, M. S., Oblong, J. E., and Lamppa, G. K. (1991) Plant Physiol. 96, 1220-1227). In this study we show that after solubilization in 6 M urea and dialysis into 20 mM Tris-HCl (pH 8.0) the recombinant LHCP precursor (preLHCP) was not found as a monomer (31 kDa), but instead produced a heterogeneous population of oligomeric complexes, ranging from 60-300 kDa as determined by gel filtration chromatography. Circular dichroism analysis indicated that the oligomers had folded structure, and that it was composed of both alpha-helix and beta-sheet. Approximately half of recombinant preLHCP found in these complexes was cleavable at the transit peptide-mature protein junction by a soluble chloroplast processing enzyme in an organelle-free reaction. At 1.5 microM the recombinant precursor inhibited the import of radiolabeled preLHCP and the precursor of the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase generated by reticulocyte lysate translations. When chloroplasts were preincubated with the precursor, followed by their reisolation, import was still blocked, providing evidence that competition between recombinant preLHCP and these substrates occurred at the chloroplast per se. Recombinant preLHCP was visualized on the envelope by immunofluorescence microscopy, and its presence there was mediated by a thermolysin-sensitive factor. PMID- 1629224 TI - Regulation of mitochondrial and microsomal phospholipid synthesis by liver fatty acid-binding protein. AB - Recently we have detected and partially purified a 15-kDa cytosolic L-alpha lysophosphatidic acid (LPA)-binding protein (LPABP), which stimulates export of LPA from mitochondria (Vancura, A., Carroll, M. A., and Haldar, D. (1991) Biochem. Biophys. Res. Commun. 175, 339-343). Now we have purified this protein to homogeneity. By Western immunoblot analysis, amino acid sequence analysis, and binding characteristics we have shown that LPABP is identical with liver fatty acid-binding protein (L-FABP). This protein binds LPA, and stimulates mitochondrial and microsomal glycerophosphate acyltransferase (GAT) and the export of LPA from both the organelles. The mitochondrially synthesized LPA exported by L-FABP can be converted to phosphatidic acid by microsomes. L-FABP also stimulates microsomal conversion of LPA to phosphatidic acid but strongly inhibits this reaction in mitochondria. However, in the absence of L-FABP mitochondria predominantly synthesize PA. Taken together, these findings are suggestive that L-FABP plays a major role in mitochondrial and microsomal phospholipid metabolism by regulating both the synthesis and utilization of LPA. PMID- 1629225 TI - Purification of BBF, a DNA-binding protein recognizing a positive cis-acting element in the mouse alpha 1(III) collagen promoter. AB - A positive cis-acting element, the B element, located between -83 and -61 in the mouse alpha 1(III) collagen promoter, binds a factor present in nuclear extracts of NIH 3T3 fibroblasts and HeLa cells. We have purified this factor using ion exchange chromatography, sequence-specific DNA affinity chromatography, and sodium dodecyl sulfate-polyacrylamide gel fractionation. The DNA sequence used for the affinity chromatography was a single-base substitution in the B element that increased the stability of the B element-protein complex by 50%. Purification of the B element-binding factor (BBF) by DNA affinity chromatography resulted in the apparent loss of most or all of the DNA-binding activity of this factor. The DNA-binding activity could, however, be reconstituted by combining two chromatographic fractions: the high-salt eluate and the column flow-through. When the partially purified high-salt eluate was size-fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with subsequent renaturation of gel fractions from guanidine HCl, the purified BBF (apparent molecular weight of about 95,000) bound to the B element with high affinity. These results suggest that during DNA affinity purification of BBF a factor that inhibits BBF DNA binding was co-eluted with BBF. This inhibition of BBF DNA binding was reversed by the addition of the DNA affinity column flow-through. The binding of BBF to the B element of the mouse alpha 1(III) collagen promoter is therefore an apparently complex process involving interactions between BBF and other protein factors. PMID- 1629226 TI - Carboxyl-terminal consensus Ser-Lys-Leu-related tripeptide of peroxisomal proteins functions in vitro as a minimal peroxisome-targeting signal. AB - The minimal sequence requirement for a peroxisome-targeting signal was investigated using an in vitro import system. Carboxyl-terminal sequences Ser-Lys Leu (SKL) and Leu-Gln-Ser-Lys-Leu (LQSKL) of acyl-CoA oxidase (AOX) directed to peroxisomes the fused proteins with import-incompetent forms of AOX and catalase that had been truncated, implying that the SKL tripeptide functions as a targeting signal. Elimination of the entire SKL sequence or deletion of any 1 or 2 amino acids in the sequence abolished the import activity of AOX. Substitution of alanine for serine did not affect the import activity. Topogenic activity was retained when lysine was mutated to either arginine or histidine, whereas mutation to glutamic acid completely abolished the activity. A synthetic peptide comprising the carboxyl-terminal 10 amino acid residues of AOX inhibited the import of the authentic AOX polypeptide, whereas other peptides in which SKL was mutated, deleted, or internally located were not effective. The uptake of AOX was little affected by the peptide with an amidated alpha-carboxyl group. These results strongly suggest that the carboxyl-terminal SKL motif sequence (Ser/Ala) (Lys/Arg/His)-Leu functions as a topogenic signal in translocation of proteins into peroxisomes, requiring the whole tripeptide sequence with a free alpha-COOH group at the carboxyl terminus. PMID- 1629227 TI - An isoform of protein disulfide isomerase isolated from chronic myelogenous leukemia cells alters complex formation between nuclear proteins and regulatory regions of interferon-inducible genes. AB - We have previously shown that the electrophoretic mobility of complexes formed in vitro between nuclear proteins and the regulatory domains of interferon-inducible genes is altered by an extranuclear protein present in elevated levels in the myeloid cells of chronic myelogenous leukemia patients. Interferon-alpha reduces the level of this activity only in the cells of patients who are clinically sensitive to the antiproliferative effects of interferon-alpha. We have purified this protein to homogeneity and found it to be a 57-kDa protein which corresponds to an isoform of protein disulfide isomerase. Protein disulfide isomerase is an oxidoreductase which catalyzes the interconversion between the reduced and oxidized states of proteins which contain multiple sulfhydryl groups and disulfide bonds. These studies suggest that this protein may play an important role in the transcriptional activation of interferon-inducible genes, perhaps through redox mechanisms. PMID- 1629228 TI - The cytoskeletal protein talin is O-glycosylated. AB - Talin is a 215-kDa cytoskeletal protein implicated in linking actin filaments to the plasma membrane. We show here that chicken gizzard talin is galactosylated by incubation with UDP-[3H]galactose and galactosyl-transferase. The labeled carbohydrate moiety is removed by beta-elimination and comigrates with Gal beta 1 4GlcNAcitol, indicating that talin belongs to a recently discovered class of cytosolic proteins carrying N-acetylglucosamine (GlcNAc) O-linked to serine or threonine (Holt, G. D., and Hart, G. W. (1986) J. Biol. Chem. 261, 8049-8057). Two glycosylated sequences were identified in the tail domain of talin: ANQAIQMAXQNLVDPAXTQ and GILANQLTNDYGQLAQQ, corresponding to amino acids 1470-1488 and 1883-1899, respectively, of the mouse talin amino acid sequence (Rees, D. J. G., Ades, S. E., Singer, S. J., and Hynes, R. O. (1990) Nature 347, 685-689). The putative glycosylation sites are PAXTQ and QLTND. At most 6% of chicken gizzard talin and 3% of porcine stomach talin are galactosylated by galactosyltransferase. Furthermore, human platelet talin is not labeled at all by the procedure, indicating that it may not be glycosylated. PMID- 1629229 TI - A novel site-directed mutant of myoglobin with an unusually high O2 affinity and low autooxidation rate. AB - Mutants of sperm whale myoglobin were constructed at position 29 (B10 in helix notation) to examine the effects of distal pocket size on the rates of ligand binding and autooxidation. Leu29 was replaced with Ala, Val, and Phe using the synthetic gene and Escherichia coli expression system of Springer and Sligar (Springer, B. A., and Sligar, S. G. (1987) Proc. Natl. Acad. Sci. U. S. A. 84, 8961-8965). Structures of the ferric forms of Val29 and Phe29, and the oxy form of Phe29 myoglobin were determined to 1.7 A by x-ray crystallography. The ferric mutant proteins are remarkably isomorphous with the wild type protein except in the immediate vicinity of residue 29. Thus, the protein structure in the distal pocket of myoglobin can accommodate either a large "hole" (i.e. Ala or Val) or a large side chain (i.e. Phe) at position 29 without perturbation of tertiary structure. Phe29 oxymyoglobin is also identical to the native oxy protein in terms of overall structure and interactions between the bound O2 and His64, Val68, Phe43, and Ile107. The distance between the nearest side chain atom of residue 29 and the second atom of the bound oxygen molecule is 3.2 A in the Phe29 protein and 4.9 A in native myoglobin. The equilibrium constants for O2 binding to Ala29, Val29, and Leu29 (native) myoglobin are the same, approximately 1.0 x 10(6) M-1 at 20 degrees C, whereas that for the Phe29 protein is markedly greater, 15 x 10(6) M-1. This increase in affinity is due primarily to a 10-fold decrease in the O2 dissociation rate constant for the Phe29 mutant and appears to be the result of stabilizing interactions between the negative portion of the bound O2 dipole and the partially positive edge of the phenyl ring. Increasing the size of residue 29 causes large decreases in the rate of autooxidation of myoglobin: k(ox) = 0.24, 0.23, 0.055, and 0.005 h-1 for Ala29, Val29, Leu29 (native), and Phe29 myoglobin, respectively, in air at 37 degrees C. Thus, the Leu29----Phe mutation produces a reduced protein that is remarkably stable and is expressed in E. coli as 100% MbO2. The selective pressure to conserve Leu29 at the B10 position probably represents a compromise between reducing the rate of autooxidation and maintaining a large enough O2 dissociation rate constant to allow rapid oxygen release during respiration. PMID- 1629230 TI - xP2, a new member of the P-domain peptide family of potential growth factors, is synthesized in Xenopus laevis skin. AB - Similarly to epidermal growth factor (EGF) and EGF-like repeats, the "P-domain" represents a cysteine-rich module that has been detected in the past in a variety of polypeptides, as well as in high molecular weight proteins. Here, a precursor for a secretory polypeptide (xP2) is characterized that consists of two P domains. xP2 has been discovered in Xenopus laevis with the help of the polymerase chain reaction. In contrast to all other P-domain peptides, it is synthesized in the skin but not in the stomach or the pancreas. By this and other criteria, it cannot be considered simply as the X. laevis homologue of recently described P-domain peptides, viz. the spasmolytic polypeptides (PSP/hSP/mSP). Furthermore, a polyclonal antiserum was generated against the deduced C-terminal end of xP2. Due to its immunoreactivity with granular glands, as well as with the epidermis, the possibility of a growth factor activity for xP2 in the germinal layer is discussed. PMID- 1629231 TI - Adipocyte differentiation of 3T3-L1 cells involves augmented expression of a 43 kDa plasma membrane fatty acid-binding protein. AB - A previously described 43-kDa plasma membrane fatty acid-binding protein (FABPPM) was not observed by immunohistochemical methods in proliferating 3T3-L1 fibroblasts. However, it was detectable in plasma membranes by the second day of confluent growth, prior to accumulation of visible lipid droplets, and was strongly expressed in 8-day differentiated adipocytes. These observations were confirmed by extraction of plasma membrane proteins and subsequent immunoblotting. Kinetics of initial [3H]oleate uptake by both fibroblasts and adipocytes consisted of the sum of a saturable and a non-saturable component. During differentiation the saturable component increased progressively. Vmax increased from 3 to 25 to 110 pmol.s-1.mg cell protein-1 between the fibroblast, the 4-day, and 8 day adipocyte stages; Km was 24 nM in fibroblasts and approximately 55 nM in both 4- and 8-day differentiated adipocytes. By contrast, the rate constant for nonsaturable oleate influx decreased progressively from 0.026 to 0.010 ml.s-1.mg protein-1 between the fibroblast and 8 day adipocyte stages. In 8-day adipocytes saturable oleate uptake was inhibited by up to 55% by antibodies against rat liver FABPPM; these antibodies had no effect on uptake of 2-deoxyglucose or the medium chain fatty acid octanoate. They also had no effect on oleate uptake by fibroblasts. These studies support the hypothesis that FABPPM is a component of a saturable transport mechanism for long chain fatty acids. PMID- 1629232 TI - Deletion of the membrane anchoring region of tissue factor abolishes autoactivation of factor VII but not cofactor function. Analysis of a mutant with a selective deficiency in activity. AB - The activation of human blood coagulation factor VII can occur by the feedback activity of either factor VIIa (autoactivation) or factor Xa. Both of these reactions are known to be enhanced by the presence of tissue factor, an integral membrane protein and the cofactor for factor VIIa. We examine here the activation of 125I-factor VII by both factor VIIa and factor Xa employing a mutant soluble form of tissue factor which has had its transmembrane and cytoplasmic domains deleted (sTF1-219). This mutant soluble tissue factor retains cofactor activity toward factor VIIa in a single-stage clotting assay but shows a strong dependence on initial plasma levels of factor VIIa (from 1 to 10,000 ng/ml) when compared to wild-type tissue factor. We show that this dependence is due to a deficiency of sTF1-219 in ability to both promote autoactivation and enhance the factor Xa catalyzed activation of 125I-factor VII. sTF1-219 does not, however, inhibit the tissue factor-independent activation of 125I-factor VII by factor Xa. The results strongly suggest that the phospholipid anchoring region of tissue factor is essential for autoactivation and beneficial for factor Xa-catalyzed activation of 125I-factor VII. In addition, when taken together with the dependence of clotting times on initial factor VIIa levels observed with sTF1-219, these results indicate that factor VII autoactivation may be of greater importance in the initiation of blood coagulation via tissue factor than has been previously realized. PMID- 1629233 TI - Acute desensitization of muscarinic receptors in the isolated guinea-pig ileal longitudinal muscle. AB - 1. The effects of acute desensitization of muscarinic receptors mediating contractile responses of the guinea-pig ileal longitudinal muscle were studied in vitro, using similar conditions for both functional and radioligand binding studies. 2. The pA2 values for a number of muscarinic antagonists (pirenzepine, methoctramine, (+/-)para-fluoro-hexahydro-siladifenidol and 4-diphenylacetoxy-N methyl piperidine-methiodide) indicated that the contractile response to carbachol was mediated through an M3 muscarinic receptor. In binding experiments the muscarinic receptor subtype population in ileal longitudinal muscle was found to be heterogeneous, consisting of approximately 77% M2 and 23% M3 receptors. 3. Pre-exposure of ileal longitudinal muscle to 10 microM carbachol for 30 min produced a reduction (28 +/- % of control maximum) in the maximum contractile response and a dextral shift in the concentration-effect curve to carbachol. Prior equilibration (60 min) with (+/-)p-F-HHSiD (1 microM), but not with methoctramine (1 microM) or pirenzepine (0.3 microM), prevented the desensitization. Desensitization under these conditions did not alter either the apparent affinity, the total number of binding sites or the relative, proportions of M2 and M3 muscarinic receptors, as determined in radioligand binding studies. Desensitization did not cause any meaningful change in either the apparent affinity of carbachol or the proportion of the high and low affinity binding sites. 4. It is concluded that desensitization of the contractile responses of the guinea-pig ileal longitudinal muscle is a result of M3 but not M2 muscarinic receptor desensitization. Acute desensitization, therefore, is not accompanied by meaningful changes in the total number of both M2 and M3 receptors or by alterations in the affinity of the receptor to ligands. PMID- 1629234 TI - Mediation of contraction by cholinergic muscarinic receptors in the ureterovesical junction. AB - 1. The muscarinic receptor profile of the sheep ureterovesical junction has been studied by means of in vitro techniques. The relative potency (pD2 = -log EC50) and maximum effect (Emax) observed with carbachol were 51-fold and 25% greater than with acetylcholine respectively. This could be due to the presence of active acetylcholinesterase in this tissue. 2. The pA2 values obtained with the muscarinic antagonists were pirenzepine (8.52), AF-DX 116 (8.05), 4-DAMP (9.41) and hexahydroxiladifenidol (8.66). The slope values of Schild plots were not significantly different from unity, indicating competitive antagonism. Furthermore, when the slopes were constrained to 1, no significant differences were found between the pA2 values. These pA2 values were similar to those observed in other mammalian smooth muscles. 3. It is concluded that muscarinic receptors in the sheep ureterovesical junction smooth muscle belong to the M1, M2 and M3 subtypes and mediate contraction of the ureterovesical junction, which suggests that during parasympathetic stimulation they might prevent vesicoureteral reflux. PMID- 1629235 TI - Post-Golgi membrane traffic: brefeldin A inhibits export from distal Golgi compartments to the cell surface but not recycling. AB - Recent studies using the fungal metabolite brefeldin A (BFA) have provided important insights into the dynamics and the organization of the ER/Golgi membrane system. Here we examined the effect of BFA on the functional integrity of the distal part of the secretory pathway, i.e., transport between trans-Golgi cisternae and the cell surface. To assay export via the constitutive pathway, we followed the movement of vesicular stomatitis virus (VSV) G glycoprotein that had been accumulated in the trans-Golgi network (TGN) by incubation of infected BHK 21 cells at 20 degrees C. Addition of BFA rapidly and reversibly inhibited cell surface transport of G protein. The block to secretion was not due to redistribution of externalized G protein to internal pools. It was also not due to collapse of TGN to the ER, since VSV G protein blocked in treated cells resided in compartments that were distinct from the ER/Golgi system. Similar effects were found with a bulk-flow marker: BFA blocked constitutive secretion of glycosaminoglycan chains that had been synthesized and sulfated in the trans Golgi cisternae. To examine export via the regulated secretory pathway, we assayed secretion of [35S]SO4 labeled secretogranin II from PC12 cells, a marker that has been used to study secretory granule budding from the TGN (Tooze, S. A., U. Weiss, and W. B. Huttner. 1990. Nature [Lond.]. 347:207-208). BFA potently inhibited secretion of sulfated secretogranin II induced by K+ depolarization. Inhibition was at the level of granule formation, since BFA had no effect on regulated secretion from preformed granules. Taken together, the results suggest that BFA blocks export via both the constitutive and the regulated pathways. In contrast, endocytosis and recycling of VSV G protein were not blocked by BFA, consistent with previous studies that endocytosis is unaffected (Misumi, Y., Y. Misumi, K. Miki, A Takatsuki, G. Tamura, and Y. Ikehara. 1986. J. Biol. Chem. 261:11398-11403). These and earlier results suggest that the exo/endocytic pathway of mammalian cells consist of two similar but distinct endomembrane systems: an ER/Golgi system and a post-Golgi system. BFA prevents forward transport without affecting return traffic in both systems. PMID- 1629236 TI - Characterization of TPM1 disrupted yeast cells indicates an involvement of tropomyosin in directed vesicular transport. AB - Disruption of the yeast tropomyosin gene TPM1 results in the apparent loss of actin cables from the cytoskeleton (Liu, H., and A. Bretscher. 1989. Cell. 57:233 242). Here we show that TPM1 disrupted cells grow slowly, show heterogeneity in cell size, have delocalized deposition of chitin, and mate poorly because of defects in both shmooing and cell fusion. The transit time of alpha-factor induced a-agglutinin secretion to the cell surface is longer than in isogenic wild-type strains, and some of the protein is mislocalized. Many of the TPM1 deleted cells contain abundant vesicles, similar in morphology to late secretory vesicles, but without an abnormal accumulation of intermediates in the delivery of either carboxypeptidase Y to the vacuole or invertase to the cell surface. Combinations of the TPM1 disruption with sec13 or sec18 mutations, which affect early steps in the secretory pathway, block vesicle accumulation, while combinations with sec1, sec4 or sec6 mutations, which affect a late step in the secretory pathway, have no effect on the vesicle accumulation. The phenotype of the TPM1 disrupted cells is very similar to that of a conditional mutation in the MYO2 gene, which encodes a myosin-like protein (Johnston, G. C., J. A. Prendergast, and R. A. Singer. 1991. J. Cell Biol. 113:539-551). The myo2-66 conditional mutation shows synthetic lethality with the TPM1 disruption, indicating that the MYO2 and TPM1 gene products may be involved in the same, or parallel function. We conclude that tropomyosin, and by inference actin cables, may facilitate directed vesicular transport of components to the correct location on the cell surface. PMID- 1629237 TI - Localization of capping protein in chicken epithelial cells by immunofluorescence and biochemical fractionation. AB - We have localized capping protein in epithelial cells of several chicken tissues using affinity-purified polyclonal antibodies and immunofluorescence. Capping protein has a distribution in each tissue coincident with proteins of the cell cell junctional complex, which includes the zonula adherens, zonula occludens, and desmosome. "En face" views of the epithelial cells showed capping protein distributed in a polygonal pattern coincident with cell boundaries in intestinal epithelium, sensory epithelium of the cochlea, and the pigmented epithelium of the retina and at regions of cell-cell contact between chick embryo kidney cells in culture. "Edge-on" views obtained by confocal microscopy of intact single intestinal epithelial cells and of retinal pigmented epithelium showed that capping protein is located in the apical region of the epithelial cells coincident with the junctional complexes. These images do not resolve the individual types of junctions of the junctional complex. Immunolabeling of microvilli or stereocilia was faint or not detectable. Capping protein was also detected in the cytoplasm of intact intestinal epithelial cells and in nuclei of cells in the pigmented retina and in the kidney cell cultures, but not in nuclei of cells of the intestinal epithelium or sensory epithelium. Biochemical fractionation of isolated intestinal epithelial cells shows capping protein in the brush border fraction, which contains the junctional complexes, and in the soluble fraction. These results are consistent with the results of the immunolabeling experiments. Highly purified microvilli of the brush borders also contained capping protein; this result was unexpected based on the low intensity of immunofluorescence staining of microvilli and stereocilia. The microvilli were not contaminated with junctional complexes, as defined by the absence of several markers for cell junctions. The cause and significance of this discrepancy is not certain at this time. Since capping protein binds the barbed end of actin filaments in vitro, we hypothesize that capping protein is bound to the barbed ends of actin filaments associated with one or more of the junctions of the junctional complex. PMID- 1629239 TI - Kinetochore microtubules in PTK cells. AB - We have analyzed the fine structure of 10 chromosomal fibers from mitotic spindles of PtK1 cells in metaphase and anaphase, using electron microscopy of serial thin sections and computer image processing to follow the trajectories of the component microtubules (MTs) in three dimensions. Most of the kinetochore MTs ran from their kinetochore to the vicinity of the pole, retaining a clustered arrangement over their entire length. This MT bundle was invaded by large numbers of other MTs that were not associated with kinetochores. The invading MTs frequently came close to the kinetochore MTs, but a two-dimensional analysis of neighbor density failed to identify any characteristic spacing between the two MT classes. Unlike the results from neighbor density analyses of interzone MTs, the distributions of spacings between kinetochore MTs and other spindle MTs revealed no evidence for strong MT-MT interactions. A three-dimensional analysis of distances of closest approach between kinetochore MTs and other spindle MTs has, however, shown that the most common distances of closest approach were 30-50 nm, suggesting a weak interaction between kinetochore MTs and their neighbors. The data support the ideas that kinetochore MTs form a mechanical connection between the kinetochore and the pericentriolar material that defines the pole, but that the mechanical interactions between kinetochore MTs and other spindle MTs are weak. PMID- 1629238 TI - Association of calmodulin and an unconventional myosin with the contractile vacuole complex of Dictyostelium discoideum. AB - mAbs specific for calmodulin were used to examine the distribution of calmodulin in vegetative Dictyostelium cells. Indirect immunofluorescence indicated that calmodulin was greatly enriched at the periphery of phase lucent vacuoles. The presence of these vacuoles in newly germinated (non-feeding) as well as growing cells, and the response of the vacuoles to changes in the osmotic environment, identified them as contractile vacuoles, osmoregulatory organelles. No evidence was found for an association of calmodulin with endosomes or lysosomes, nor was calmodulin enriched along cytoskeletal filaments. When membranes from Dictyostelium cells were fractionated on equilibrium sucrose density gradients, calmodulin cofractionated with alkaline phosphatase, a cytochemical marker for contractile vacuole membranes, at a density of 1.156 g/ml. Several high molecular weight calmodulin-binding proteins were enriched in the same region of the gradient. One of the calmodulin-binding polypeptides (molecular mass approximately 150 kD) cross-reacted with an antiserum specific for Acanthamoeba myosin IC. By indirect immunofluorescence, this protein was also enriched on contractile vacuole membranes. These results suggest that a calmodulin-binding unconventional myosin is associated with contractile vacuoles in Dictyostelium; similar proteins in yeast and mammalian cells have been implicated in vesicle movement. PMID- 1629240 TI - A fibronectin self-assembly site involved in fibronectin matrix assembly: reconstruction in a synthetic peptide. AB - The active form of fibronectin is its extracellular matrix form, which allows for the attachment of cells and influences both the growth and migration of cells. The matrix form is assembled by cells; however, many cells are defective in this regard. Several regions within fibronectin have been shown to play a role in matrix assembly by cells. One such region has been localized into the first type III repeat of fibronectin (Chernousov, M. A., F. J. Fogerty, V. E. Koteliansky, and D. F. Mosher. J. Biol. Chem. 266:10851-10858). We have identified this site as a fibronectin-fibronectin binding site and reproduced it as a synthetic peptide. This site is contained in a 14-kD fragment that corresponds to portions of the first two type III repeats. The 14-kD fragment was found to bind to cell monolayers and to inhibit fibronectin matrix assembly. The 14-kD fragment only slightly reduced the binding of fibronectin to cell surfaces but it significantly inhibited the subsequent incorporation of fibronectin into the extracellular matrix. The 14-kD fragment also bound to purified fibronectin and inhibited fibronectin-fibronectin binding. A synthetic 31-amino acid peptide (P1) representing a segment of the 14-kD fragment retained the ability to inhibit fibronectin-fibronectin binding. Peptide P1 specifically bound fibronectin from plasma in affinity chromatography, whereas a column containing another peptide from the 14-kD fragment did not. These results define a fibronectin-fibronectin binding site that appears to promote matrix assembly by allowing the assembly of fibronectin molecules into nascent fibrils. The 14-kD fragment and the P1 peptide that contain this site inhibit matrix assembly by competing for the fibronectin fibronectin binding. PMID- 1629241 TI - Coordinate role for cell surface chondroitin sulfate proteoglycan and alpha 4 beta 1 integrin in mediating melanoma cell adhesion to fibronectin. AB - Cellular recognition and adhesion to the extracellular matrix (ECM) has a complex molecular basis, involving both integrins and cell surface proteoglycans (PG). The current studies have used specific inhibitors of chondroitin sulfate proteoglycan (CSPG) synthesis along with anti-alpha 4 integrin subunit monoclonal antibodies to demonstrate that human melanoma cell adhesion to an A-chain derived, 33-kD carboxyl-terminal heparin binding fragment of human plasma fibronectin (FN) involves both cell surface CSPG and alpha 4 beta 1 integrin. A direct role for cell surface CSPG in mediating melanoma cell adhesion to this FN fragment was demonstrated by the identification of a cationic synthetic peptide, termed FN-C/H-III, within the fragment. FN-C/H-III is located close to the amino terminal end of the fragment, representing residues #1721-1736 of intact FN. FN C/H-III binds CSPG directly, can inhibit CSPG binding to the fragment, and promotes melanoma cell adhesion by a CSPG-dependent, alpha 4 beta 1 integrin independent mechanism. A scrambled version of FN-C/H-III does not inhibit CSPG binding or cell adhesion to the fragment or to FN-C/H-III, indicating that the primary sequence of FN-C/H-III is important for its biological properties. Previous studies have identified three other synthetic peptides from within this 33-kD FN fragment that promote cell adhesion by an arginyl-glycyl-aspartic acid (RGD) independent mechanism. Two of these synthetic peptides (FN-C/H-I and FN-C/H II) bind heparin and promote cell adhesion, implicating cell surface PG in mediating cellular recognition of these two peptides. Additionally, a third synthetic peptide, CS1, is located in close proximity to FN-C/H-I and FN-C/H-II and it promotes cell adhesion by an alpha 4 beta 1 integrin-dependent mechanism. In contrast to FN-C/H-III, cellular recognition of these three peptides involved contributions from both CSPG and alpha 4 integrin subunits. Of particular importance are observations demonstrating that CS1-mediated melanoma cell adhesion could be inhibited by interfering with CSPG synthesis or expression. Since CS1 does not bind CSPG, the results suggest that CSPG may modify the function and/or activity of alpha 4 beta 1 integrin on the surface of human melanoma cells. Together, these results support a model in which the PG and integrin binding sites within the 33-kD fragment may act in concert to focus these two cell adhesion receptors into close proximity on the cell surface, thereby influencing initial cellular recognition events that contribute to melanoma cell adhesion on this fragment. PMID- 1629243 TI - How do cells sense and respond to adhesive contacts? Diffusion-trapping of laterally mobile membrane proteins at maturing adhesions may initiate signals leading to local cytoskeletal assembly response and lamella formation. PMID- 1629242 TI - Topology and phosphorylation of soybean nodulin-26, an intrinsic protein of the peribacteroid membrane. AB - Soybean nodulin-26, a homologue of bovine eye lens major intrinsic protein (MIP 26), is an integral protein of the peribacteroid membrane in symbiotic root nodules. It comprises 271 amino acids with six potential transmembrane domains and lacks an amino-terminal signal sequence. A full-length nodulin-26 cDNA and its various deletion derivatives were transcribed in vitro after linking them to bacteriophage T3 promoter. In vitro translation of these transcripts in a rabbit reticulocyte lysate, in the presence or absence of canine pancreatic microsomal membranes, suggested that nodulin-26 is cotranslationally inserted into the microsomes without a cleavable signal peptide. The first two transmembrane domains (103 amino acids) of the protein are sufficient for microsomal membrane insertion. Membrane-translocated nodulin-26 binds to Con-A and is sensitive to endoglycosidase-H treatment, suggesting that it is glycosylated. Native nodulin 26 from root nodules retains its sugar moiety as it, too, binds to Con-A. Chemical cleavage mapping at cysteine residues, a trypsin protection assay, and the Con-A binding affinity of nodulin-26 suggested that both the NH2 and COOH termini of this protein are on the cytoplasmic surface of the peribacteroid membrane, while the glycosidic residue is on the surface of the membrane facing the bacteroids. In vitro phosphorylation experiments showed that nodulin-26 is a major phosphorylated protein in the peribacteroid membrane. This phosphorylation is mediated by a Ca(2+)-dependent, calmodulin-independent protein kinase located in the peribacteriod membrane. Externally supplied acid phosphatase dephosphorylates this protein, but alkaline phosphatase does not. Based on its homology with several eukaryotic and prokaryotic channel-type membrane proteins, nodulin-26 may form a channel translocating specific molecules to the bacteroids during endosymbiosis in legume plants. PMID- 1629244 TI - Visualization of centromeric and nucleolar DNA in fission yeast by fluorescence in situ hybridization. AB - The nucleolar and centromeric DNAs of the fission yeast Schizosaccharomyces pombe were visualized in the nucleus by fluorescence in situ hybridization using repetitive ribosomal and centromeric DNAs as the probes. The rDNAs were seen in the nuclear domain previously assigned as nucleolar, that is, the region into which the rod-like chromatin protrudes from the hemispherical chromosomal domain. Using mitotically-arrested cells containing condensed chromosomes, it was demonstrated that the rDNAs were present on the smallest chromosome III, consistent with genetic data. Using a centromeric repetitive element as the hybridization probe, the centromere of chromosome III, cen3, which contains the largest number of the repetitive elements, was visualized. The centromere in interphase cells is located near the periphery of the nucleus as a single dot. Early in mitosis, however, it divides into two and is situated in the middle of the short mitotic spindle. After spindle extension in anaphase, the centromeric DNA is present at both ends of the spindle, that is, near the spindle pole bodies. The movement of cen3 during mitosis (anaphase A and B) is discussed in relation to spindle dynamics and chromosome separation. PMID- 1629245 TI - Protein kinase C involvement in focal adhesion formation. AB - Matrix molecules such as fibronectin can promote cell attachment, spreading and focal adhesion formation. Although some interactions of fibronectin with cell surface receptors have now been identified, the consequent activation of intracellular messenger systems by cell/matrix interactions have still to be elucidated. We show here that the kinase inhibitors H7 and HA1004 reduce focal adhesion and stress fiber formation in response to fibronectin in a dose dependent manner, and that activators of protein kinase C can promote their formation under conditions where they do not normally form. Fibroblasts spread within 1h on substrata composed of fibronectin and formed focal adhesions by 3h, as monitored by interference reflection microscopy (IRM) and by labeling for talin, vinculin and integrin beta 1 subunits. In addition, stress fibers were visible. When cells were allowed to spread for 1h and then treated with kinase inhibitors H7 and HA1004 for 2h, IRM indicated a reduction in focal adhesion formation at concentrations where protein kinase C (PKC) should be inhibited. In contrast, focal adhesions formed normally at concentrations of these inhibitors where cyclic AMP- or cyclic GMP-dependent kinases should be inactivated. Inhibition of PKC, but not that of cyclic AMP- or cyclic GMP-dependent kinases, also prevented the formation of stress fibers and induced a dispersal of talin and vinculin, but not integrin beta 1 subunits, from small condensations present at 1h. Consistent with the reduction in focal adhesion formation when PKC was inhibited, activation of PKC by 30 minutes of treatment with phorbol esters induced focal adhesion formation in cells spread for 3h on substrata composed of the cell-binding (RGD-containing) fragment of fibronectin, while untreated cells or those treated with inactive phorbol esters did not form these structures. PMID- 1629246 TI - Isolation of a sea urchin egg kinesin-related protein using peptide antibodies. AB - To understand the roles of kinesin and its relatives in cell division, it is necessary to identify and characterize multiple members of the kinesin superfamily from mitotic cells. To this end we have raised antisera to peptides corresponding to highly conserved regions of the motor domains of several known members of the kinesin superfamily. These peptide antibodies react specifically with the motor domains of kinesin and ncd protein, as expected, and they also react with several polypeptides (including kinesin heavy chain) that cosediment with microtubules (MTs) precipitated from AMPPNP-treated sea urchin egg cytosol. Subsequent fractionation of ATP eluates of these MTs yields a protein of relative molecular mass 330 x 10(3) that behaves as a complex of three polypeptides that are distinct from conventional kinesin subunits or fragments thereof. This complex contains 85 kDa and 95 kDa polypeptides, which react with our peptide antibodies, and a 115 kDa polypeptide, which does not. This triplet of polypeptides, which we refer to as KRP(85/95), binds to purified sea urchin egg tubulin in an AMPPNP-enhanced, ATP-sensitive manner and induces the formation of microtubule bundles. We therefore propose that the triplet corresponds to a novel sea urchin egg kinesin-related protein. PMID- 1629248 TI - Bone-marrow-derived chondrogenesis in vitro. AB - Bone marrow stromal cells from embryonic, neo-natal and adult chickens were grown in vitro over a 21-day period. Marrow stromal cells from embryonic and neonatal chicks produced clonally derived chondrocytic colonies. The cells within the colonies were surrounded by a refractile, Alcian-blue-positive matrix and their cartilagenous nature was shown biochemically and immunocytochemically by the synthesis of collagen types II and X. The ability of chick bone marrow cells to form chondrocytic colonies decreased during development and was lost by adulthood. In addition to chondrocytic colonies, fat cells and fibroblasts were also observed in the cultures. Our data demonstrate that chick bone marrow stroma contains cells that are capable of differentiating along different pathways within the same culture, providing further evidence for the presence in bone marrow of a stromal stem cell. PMID- 1629247 TI - Evidence for kinesin-related proteins in the mitotic apparatus using peptide antibodies. AB - To identify kinesin-related proteins that may be important for mitotic function in embryonic and tissue culture cells we have generated polyclonal antibodies to two synthetic peptides corresponding to conserved regions of the kinesin motor domain. In Xenopus eggs we have identified a family of microtubule-binding proteins, recognized by one or both affinity-purified peptide antibodies but not by monoclonal antibodies that recognize conventional kinesin heavy chain. Like kinesin, most of these proteins bind to microtubules only upon addition of AMP PNP or nucleotide depletion and are released upon subsequent addition of ATP. At least one protein, however, exhibits markedly distinct properties, binding readily to microtubules in the absence of AMP-PNP and/or nucleotide depletion. We also report that, unlike antibodies to conventional kinesin, the peptide antibodies to the kinesin motor domain immunofluorescently label spindles and kinetochores in mitotic tissue culture cells, suggesting that kinesin-like proteins may have important roles in chromosome movement and mitosis. PMID- 1629249 TI - Transport of the cationic fluorochrome rhodamine 123 in an insect's Malpighian tubule: indications of a reabsorptive function of the secondary cell type. AB - The pathway of rhodamine 123 was examined after injection into Sarcophaga flies and after in vitro labeling of the Malpighian tubules. After in vitro labeling the primary cells only retained this potential-sensitive dye for a short period while all secondary cells accumulated the dye from the tubule lumen. In vivo the secondary cells also accumulated rhodamine 123 from the lumen, but the primary cells in the distal parts of all four tubules retained the dye for prolonged periods. This was most pronounced in the distal part of the anterior Malpighian tubules, where rhodamine 123 was eventually precipitated on the luminal concretions. Rhodamine 123 initially accumulated in the secondary cell mitochondria and eventually in intensely fluorescing vesicles, probably lysosomes. No evidence for endocytotic processes from the lumen was found using Lucifer Yellow CH, fluorescent dextrans and fluorescent albumin. Prior incubation with the ionophores valinomycin, nigericin, CCCP (all 1 micrograms/ml), dinitrophenol (1 mM) and NaN3 (10(-2) M) inhibited the selective accumulation of rhodamine 123 to a large extent while monensin (1-5 micrograms/ml) showed little inhibitory effect. Furthermore, only cationic and no anionic or neutral dyes were accumulated by the secondary cells. In the fleshfly Calliphora and the fruitfly Drosophila, the dye rhodamine 123 also selectively accumulated in the secondary cells, as well in vitro as in vivo. PMID- 1629250 TI - Salt-stable interaction of the amino-terminal head region of vimentin with the alpha-helical rod domain of cytoplasmic intermediate filament proteins and its relevance to protofilament structure and filament formation and stability. AB - Previous studies have shown that the non-alpha-helical, amino-terminal head region of vimentin is essential for the formation and stability of vimentin intermediate filaments (IFs). In order to specify its target site on companion protein subunits, it was cut off from vimentin at amino acid position 96 with lysine-specific endoproteinase and allowed to react with intact vimentin and other IF proteins. In solution of high salt concentration (500 mM KCl), the isolated polypeptide (vim NT) showed a high affinity for all cytoplasmic IF proteins tested, but not for nuclear lamins. Employing limited digestion of the IF proteins with different proteinases, the binding site was shown to reside in their alpha-helical rod domains. Other polypeptides possessing alpha-helical regions with the potential to form coiled-coil structures like tropomyosin and myosin subfragment 2 did not react with vim NT. The binding to IF proteins was strongly inhibited by phosphorylation of vim NT and totally abolished in the presence of 200 mM arginine hydrochloride, whereas the same concentration of lysine hydrochloride was ineffective. Limited chymotryptic digestion of vim NT produced polypeptides that were unable to react with the alpha-helical region of vimentin at high salt concentration. Consistent with these observations, vim NT strongly inhibited filament formation in vitro from protofilamentous vimentin. A 14-mer oligopeptide comprising the amino acids 3 to 16 of the amino terminus also inhibited filament formation, though to a lesser extent. Conversely, vim NT and, with a lower efficiency, the 14-mer oligopeptide also severely affected the structure of preformed vimentin filaments by unraveling them. Phosphorylated vim NT was considerably less active in this respect. Further digestion of the rod domain of vimentin with chymotrypsin yielded 17.4 and 21 kDa polypeptides, which were tentatively characterized as originating from the carboxy- and amino terminal half of the rod domain, respectively. Both formed salt-stable complexes with vim NT, the smaller polypeptide with a higher efficiency than the larger one. These results suggest that the staggered, antiparallel arrangement of the two coiled-coils in the protofilaments of IF proteins is, at least in part, determined by the twofold, symmetrical association of the amino-terminal head regions of one coiled-coil rope structure with the carboxy-terminal halves of the alpha-helical rod domains of the other coiled-coil and that similar interactions occur during filament assembly and in the intact filament. PMID- 1629251 TI - Attachment of steroidogenic lipid droplets to intermediate filaments in adrenal cells. AB - Light microscopy of living and extracted adrenal cells (Y-1 mouse adrenal tumour cells and cultured bovine fasciculata cells), using Nomarski optics and fluorescence with nile red to stain lipid, revealed in both cell types that lipid droplets remain attached to intermediate filaments when the cells are extracted to prepare these structures. Electron microscopy of thin sections shows the presence of lipid droplets in both cell types. The droplets differ in appearance but are, in both cases, surrounded by a complete capsule 5 nm wide. The droplets in Y-1 cells include those associated with lysosomes and crystalline structures in addition to typical rounded forms. Only the latter type is seen in bovine fasciculata. Intermediate filaments apparently ending in droplets can also be seen. Immunoelectron microscopy with anti-vimentin and Protein A conjugated to gold particles together with measurement of the diameter of these structures identifies them as intermediate filaments. When adrenal cells are permeabilised and extracted under mild or severe conditions using Triton X-100, thin sections showed that lipid droplets remain associated with the cytoskeleton and in particular intermediate filaments. Extraction under mild and severe conditions cleared the cell contents, revealing attachment of intermediate filaments to lipid droplets with greater clarity than in unextracted cells, i.e. homogenised cells or cells subjected to lysis. Such attachment was unequivocally demonstrated in stereo pairs. These observations support our earlier studies showing attachment of droplets to intermediate filaments, which suggests a role for these filaments in intracellular transport of cholesterol. PMID- 1629252 TI - Alpha-actinin and vinculin in human neutrophils: reorganization during adhesion and relation to the actin network. AB - We have studied the reorganization of vinculin and alpha-actinin during the process of adhesion in human neutrophils using immunofluorescence microscopy and interference reflection microscopy (IRM). Neutrophils in contact with uncoated glass formed black IRM areas in the cell periphery, indicative of very close contact with the substratum. Eight to twelve minutes after addition of cells to glass, vinculin was found to become concentrated in small patches at the cell periphery, partially colocalizing with the black IRM areas and with small F-actin containing adherent protrusions. In contrast, vinculin was not significantly enriched in the less adherent F-actin-rich large pseudopods. alpha-Actinin became enriched during cell adhesion in retraction fibers and, in 40-50% of the inspected cells, also in large less adherent pseudopods where it colocalized with F-actin. The latter finding suggests a continuous dynamic reorganization of pseudopods, with incorporation of alpha-actinin at a certain stage. Disruption of the actin network with cytochalasin D revealed a differential interaction of alpha-actinin and vinculin with the actin network. alpha-Actinin was strongly influenced by cytochalasin D, comparable to F-actin, and both proteins formed colocalizing peripheral caps in 10(-5) M of the drug. Vinculin organization in contrast was not affected by up to 10(-6) M cytochalasin. At 10(-5) M of the drug, however, the patches disappeared completely, vinculin now assuming a diffuse cytoplasmic location. Our results suggest a specialized function of vinculin in adhesion sites of human neutrophils, whereas alpha-actinin may structure the actin network in retraction fibers and in less adherent pseudopods. PMID- 1629253 TI - Tracking of cell surface receptors by fluorescence digital imaging microscopy using a charge-coupled device camera. Low-density lipoprotein and influenza virus receptor mobility at 4 degrees C. AB - A fluorescence imaging system, based on using a cooled slow-scan CCD camera, has been developed for tracking receptors on the surfaces of living cells. The technique is applicable to receptors for particles such as lipoproteins and viruses that can be labeled with a few tens of fluorophores. The positions of single particles in each image are determined to within 25 nm by fitting the fluorescence distribution to a two-dimensional Gaussian function. This procedure also provides an accurate measure of intensity, which is used as a tag for automated tracking of particles from frame to frame. The method is applied to an investigation of the mobility of receptors for LDL and influenza virus particles on human dermal fibroblasts at 4 degrees C. In contrast to previous studies by FRAP (fluorescence recovery after photo-bleaching), it is found that receptors have a low but measurable mobility at 4 degrees C. Analysis of individual particle tracks indicates that whilst some receptors undergo random diffusion, others undergo directed motion (flow) or diffusion restricted to a domain. A procedure is proposed for subdividing receptors according to their different types of motion and hence determining their motional parameters. The finding that receptors are not completely immobilised at 4 degrees C is significant for studies of receptor distributions performed at this temperature. PMID- 1629254 TI - Localised application of an activating signal to a cell: experimental use of fibronectin bound to beads and the implications for mechanisms of adhesion. AB - Small beads derivatised with fibronectin or with bovine serum albumin are allowed to attach to BHK cells in suspension at low ratios of beads to cells. In this way populations of cells bearing predominantly one bead per cell can be prepared. We show that the attachment of one bead per cell affects the adhesion and spreading of that cell on substrata, raising adhesion and increasing spreading if the signal molecule is fibronectin, decreasing these quantities if the bead bears BSA. The experiments are conducted in the absence of other sources of exogenous fibronectin and in some cases in the additional absence of endogenous sources. The effects are especially marked if the substratum is adsorbed haemoglobin on which control cells show little attachment or spreading. We further show by interference reflection microscopy and by scanning electron microscopy that the beads are found on the non-adhering side (uppermost or outer) of the cell when fibronectin-bearing beads are used, presumably because fibronectin will not attach to haemoglobin. The increased adhesion and spreading found in such cases must be attributed to an activation produced by the bead, which spreads to other parts of the cell and which activates a fibronectin-independent mode of adhesion. PMID- 1629255 TI - Endosomal system of Paramecium: coated pits to early endosomes. AB - A detailed morphological and tracer study of endocytosis via coated pits in Paramecium multimicronucleatum was undertaken to compare endocytic processes in a free-living protozoon with similar processes in higher organisms. Permanent pits at the cell surface enlarge, become coated and give rise to coated vesicles (188 +/- 41 nm in diameter) that enclose fluid-phase markers such as horseradish peroxidase (HRP). Both the pits and vesicles are labeled by the immunogold technique when a monoclonal antibody (mAb) raised against the plasma membrane of this cell is applied to cryosections. The HRP is delivered to an early endosome compartment, which also shares the plasma membrane antigen. The early endosome, as shown in quick-freeze deep-etch replicas of chemically unfixed cells, is a definitive non-reticular compartment composed of many individual flattened cisternal units of 0.2 to 0.7 microns diameter, each potentially bearing one or more approximately 80-nm-wide coated evaginations. These coated evaginations on the early endosomes contain HRP but are not labeled by the mAb. The coated evaginations pinch off to form a second group of coated vesicles (90 +/- 17 nm in diameter), which can be differentiated from those formed from coated pits by their smaller size, absence of plasma membrane antigen and their location somewhat deeper into the cytoplasm. This study shows a striking similarity between protozoons and mammalian cells in their overall early endosomal machinery and in the ability of early endosomes to sort cargo from plasma membrane components. The vesicles identified in this study form two distinct populations of putative shuttle vesicles, pre-endosomal (large) and early endosome-derived vesicles (small), which facilitate incoming and outgoing traffic from the early endosomes. PMID- 1629256 TI - Cloning and expression of Drosophila HP1 homologs from a mealybug, Planococcus citri. AB - The mealybug chromosome cycle is one of the most dramatic examples of genomic imprinting known. In embryos that are to become male the entire paternal chromosome set becomes heterochromatic and inactive at the blastoderm stage, while the maternal set remains active and euchromatic. HP1 is a protein from Drosophila melanogaster, which binds preferentially to heterochromatin on polytene chromosomes and is likely to be a modifier of position effect variegation. This paper describes the isolation and sequencing of two cDNA clones encoding HP1 homologs from the mealybug, Planococcus citri. The protein product of the cDNA clone that was closer to HP1 in sequence was expressed as a fusion protein in Escherichia coli, and polyclonal rat antibodies were raised against it. Immunohistochemistry to mealybug squash preparations showed that this protein was a male-specific nuclear protein, but that it was not specifically associated with the heterochromatic set of chromosomes. PMID- 1629257 TI - Ambulatory blood pressure monitoring: clinical uses. AB - Ambulatory monitoring is a strategy that may effectively address the phenomenon of "white coat" hypertension and determine whether the peaks and troughs that typify circadian variations should be considerations in blood pressure management. In selected patients, ABPM may indeed be useful both for diagnosing hypertension and for monitoring response to therapy. PMID- 1629258 TI - Non-Q-wave myocardial infarction: a prognostic paradox. AB - It is now clear that non-Q-wave MI, whose incidence appears to be rising, carries an increased risk of reinfarction and recurrent ischemia. Indeed, non-Q-wave late mortality may equal or exceed that of its Q-wave counterpart. The management question: Should the patient with non-Q-wave MI have myocardial revascularization or strictly medical therapy? PMID- 1629259 TI - Scientific paper or political 'white paper'? PMID- 1629260 TI - Of birds and blood cells. Bruce Glick unravels the secret of the bursa of Fabricius. PMID- 1629261 TI - Primary hyperparathyroidism: problems in management. AB - Most hyperparathyroidism is subclinical, with no complaints of bone pain, constipation, mental confusion, or depression, no skeletal findings on x-ray, and no history of kidney stones. Routine hyperparathyroidectomy for asymptomatic hypercalcemia, with normal bone density and normal calciuria, particularly with moderate elevations of serum calcium, is now generally rejected. PMID- 1629262 TI - A partnership of patient, physician, and payer. PMID- 1629263 TI - Framing disease: studies in cultural history. Introduction. Framing disease: illness, society, and history. PMID- 1629264 TI - A new vista in Natchitoches. PMID- 1629265 TI - Framing disease: studies in cultural history. From Bright's disease to end-stage renal disease. PMID- 1629266 TI - Acute suppurative parotitis in a middle-aged woman. PMID- 1629267 TI - A slow pulse and a loud murmur in an elderly woman. PMID- 1629268 TI - The ups and downs of gastroesophageal reflux disease. PMID- 1629269 TI - Occult constipation. PMID- 1629270 TI - Malnutrition in the elderly. PMID- 1629271 TI - Studies on steroids. CCLIV. Gas chromatographic-mass spectrometric determination of 4- and 6-hydroxylated bile acids in human urine with negative ion chemical ionization detection. AB - A method for the determination of 4- and 6-hydroxylated bile acids with a vicinal glycol moiety in human urine by gas chromatography-mass spectrometry with negative ion chemical ionization detection is described. The 4 beta-hydroxylated bile acids labelled with 18O and 2H were prepared as internal standards by the exchange reaction of the carbonyl group on the steroid nucleus with H2(18)O, followed by metal deuteride reduction. Bile acids in urine were extracted with a Sep-Pak C18 cartridge and, after solvolysis and hydrolysis of the conjugated forms, transformed into pentafluorobenzyl ester diethylhydrogensilyl ether diethylsilylene derivatives. Subsequent resolution into individual 4- and 6 hydroxylated bile acids was carried out on a cross-linked fused-silica capillary column; a characteristic carboxylate anion, [M-PFB]-, was used to monitor each bile acid in the negative ion mode. The newly developed method was applied to the separation and determination of 4- and 6-hydroxylated bile acids in a urine specimen from a newborn infant. PMID- 1629272 TI - Determination of fluvoxamine in human plasma by high-performance liquid chromatography with fluorescence detection. AB - Fluvoxamine and nortriptyline, the assay internal standard, were extracted from plasma with ethyl acetate, then reacted with dansyl chloride. The derivatives were quantitated by isocratic reversed-phase high-performance liquid chromatography with fluorescence detection. The assay calibration range for fluvoxamine was 10-1000 ng/ml using a 1-ml plasma sample. Pooled plasma quality control sample relative recoveries at 25 and 250 ng/ml were 103 and 105%, respectively. Estimates of quality control inter-day precision during validation were less than or equal to 3% relative standard deviation. The assay was cross validated with a gas chromatographic method and has been employed in therapeutic drug level monitoring. PMID- 1629273 TI - Simultaneous determination of free catecholamines and epinine and estimation of total epinine and dopamine in plasma and urine by high-performance liquid chromatography with fluorimetric detection. AB - Epinine (N-methyldopamine) is the pharmacologically active hydrolysis product of the prodrug ibopamine, which is currently being widely studied for the treatment of congestive heart failure. This paper reports a sensitive and reliable method for the simultaneous determination of free catecholamines and epinine in plasma and urine. The compounds are isolated from plasma or urine by a specific liquid liquid extraction, derivatized with the selective fluorogenic agent 1,2 diphenylethylenediamine, and quantitated by high-performance liquid chromatography with gradient elution and fluorimetric detection. The limits of detection for the derivatized catecholamines and epinine are 0.3-0.6 pg of injected compound. Intra- and inter-assay coefficients of variation of all four compounds are good (1-8%), as are the accuracy and linearity. A method is also reported for the determination of total dopamine and epinine in plasma and urine based on the same principle. This method, in which deconjugation is accomplished by acid hydrolysis at 95 degrees C, also shows good sensitivity and reproducibility. PMID- 1629274 TI - Direct analysis of whole blood by internal surface reversed-phase chromatography: an examination of the binding and metabolism of technetium dioxime complexes. AB - We have developed a method using internal surface reversed-phase (ISRP) packing for rapid on-line separation of small hydrophobic compounds from cellular whole blood components. This is achieved by the use of 75-microns ISRP chromatographic material packed into a small high-performance liquid chromatographic (HPLC) column, in conjunction with column switching. We have applied this analytical method to study the in vitro metabolism of 99mTc-BATO (boronic acid adducts of technetium dioxime) cerebral and myocardial perfusion tracers in whole blood. The results from the ISRP procedure were compared with a conventional centrifugation method of analysis. This novel HPLC methods provides a rapid, convenient and reliable method for the analysis of radioactive and non-radioactive lipophilic components in whole blood. PMID- 1629275 TI - Determination of cicletanine enantiomers in plasma by high-performance capillary electrophoresis. AB - A sensitive and selective high-performance capillary electrophoresis procedure was developed for the determination of S(+) and R(-) enantiomers of cicletanine in human plasma. The procedure consisted in extraction of the drug with diethyl ether and analysis by micellar electrokinetic capillary chromatography in a fused silica capillary using gamma-cyclodextrins in the run buffers and ultraviolet detection. The method was linear from 10 to 500 ng/ml and the limit of detection was 10 ng/ml for each enantiomer in plasma samples. The within-run precision of the method, expressed as relative standard deviation, was 10.4 and 9.6% at 25 ng/ml for S(+) and R(-) cicletanine, and 4.2 and 4.6% at 500 ng/ml, respectively. This method has been used to follow the time course of the concentrations of the cicletanine enantiomers in human plasma after a single therapeutic dose of cicletanine given by mouth. PMID- 1629276 TI - Standardization in the determination of red blood cell polyamines by high performance liquid chromatography. AB - The choice of the standardization method in the high-performance liquid chromatographic determination of dansyl polyamines (spermidine and spermine) in red blood cell extracts is discussed. 1,6-Hexanediamine, commonly used as an internal standard, is unsuitable for the quantification of spermidine and spermine in red blood cells because their percentage recoveries are significantly different (100% for 1,6-hexanediamine, and 70% for spermidine and spermine). The external standard method and the standard addition method are better suited. The procedure for the preparation of the standard mixture before dansylation has an influence on the values of red blood cell polyamines. Two procedures are compared and the corresponding percentages of variation were found to be high for spermidine and spermine. Thus the procedure in which the standard is treated in a strictly similar way as the red blood cells is certainly the most appropriate one for the quantification. PMID- 1629277 TI - Improved method for the determination of 5,6-dihydroxytryptamine and 5,7 dihydroxytryptamine in tissue using high-performance liquid chromatography with electrochemical detection. AB - A liquid chromatographic method with electrochemical detection is described for the determination of the 5-hydroxytryptamine (5-HT) neurotoxins 5,6 dihydroxytryptamine (5,6-DHT) and 5,7-dihydroxytryptamine (5,7-DHT) in rat brain tissue. This method has also been used for the determination of 5 hydroxyindoleacetic acid, homovanillic acid and 5-HT in other tissue samples. The method is based on extraction of the indoles from brain samples with perchloric acid followed by reversed-phase liquid chromatography with electrochemical detection. The detection limit is 1 ng per 100 mg of tissue. This paper describes a quick and reliable method of assaying the 5-HT neurotoxins 5,6-DHT and 5,7-DHT in brain tissue, which is improved compared to currently available assays. PMID- 1629278 TI - Study of the measurement of chondroitin sulphates in rabbit plasma and serum. AB - A highly sensitive high-performance liquid chromatography method, which was established by us for the determination of chondroitin sulphates in biological substances as their unsaturated disaccharides, was applied to elucidate the qualitative and quantitative differences in chondroitin sulphates in rabbit plasma and serum samples. In this work, it was found that rabbit plasma contains low-sulphated chondroitin 4-sulphate (approximately 40% sulphation at the 4 position of N-acetyl galactosamine), while serum contains the low-sulphated chondroitin 4-sulphate and fully sulphated chondroitin 4-sulphate (approximately 96% sulphation). The latter was released from platelets during coagulation of blood. PMID- 1629279 TI - Tissue sulfate determination by ion chromatography. AB - The application of controlled-flow anion chromatography to assay inorganic sulfate in biological fluids and tissues is described. The eluent used in previous methods for analyzing sulfate in biological fluids has been modified by adding 4.5% acetonitrile to separate sulfate from a co-eluting peak. To markedly increase the life of the column, the tissue samples were further diluted, extracted with chloroform, and analyzed at a lower detection range (0.3 microS). The method has been shown to be applicable for determining sulfate in tissues as well as biological fluids. PMID- 1629280 TI - Rapid and selective isolation of radiolabelled inositol phosphates from cancer cells using solid-phase extraction. AB - A method is described for rapid and selective determination of radiolabelled inositol phosphates in cancer cells using solid-phase extraction with Bond Elut strong anion-exchange minicolumns. The inositol phosphates IP1, IP2 and IP3 are selectively eluted with 0.05, 0.3 and 0.8 M ammonium formate-0.1 M formic acid, respectively. Cancer cells are extracted with 10% perchloric acid which is then neutralised prior to loading samples on to the minicolumns. Recovery is 54.1, 66.6 and 61.3% for IP1, IP2 and IP3 with between-day coefficients of variation of 7.6, 6.8 and 1.9%, respectively. When the method was applied to cancer cells high performance liquid chromatographic analyses confirmed both the identity of the IP1, IP2 and IP3 fractions and showed that there was no detectable cross contamination of these inositol phosphates with each other. PMID- 1629281 TI - Determination of 8-methoxypsoralen in plasma by gas chromatography-mass spectrometry using selected-ion monitoring. AB - A sensitive and accurate assay was developed for the measurement of 8 methoxypsoralen in plasma using electron-impact positive-ion mass fragmentography. 4,5,8-Trimethylpsoralen was used as an internal standard. Sample preparation consisted of a two-step liquid phase extraction using acetonitrile and methylene chloride. The calibration curve showed a linear relationship between the peak areas of 8-methoxypsoralen and 4,5,8-trimethylpsoralen over a wide range of 8-methoxypsoralen concentrations (1-500 ng/ml). With-in- and between-run precisions, measured at five different drug concentrations, varied from 0.82 to 1.41% and from 0.82 to 1.86%, respectively. PMID- 1629282 TI - Determination of 4-aminopyridine in serum by solid-phase extraction and high performance liquid chromatography. AB - An assay for the determination of 4-aminopyridine in serum has been developed using 3,4-diaminopyridine as internal standard and reversed-phase high performance liquid chromatography with detection at 244 nm. A mobile phase of acetonitrile-methanol-ethanol-1% ammonium carbonate (75:10:10:5) provided excellent separation of both compounds. Samples were extracted on solid-phase columns. The linearity, precision, recovery and the limit of detection were all sufficient for the routine use of this assay in clinical studies of patients treated with 4-aminopyridine. PMID- 1629283 TI - Monitoring of the uptake and metabolism of aminooxy analogues of polyamines in cultured cells by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method for the determination of polyamines and their aminooxy analogues is described. Oxime derivatization with a ketone is used to protect the aminooxy group during post-column reaction with o phthalaldehyde. The amount of the polyamines and of the oximes of their aminooxy analogues can be determined simultaneously in cultured cells and cell culture media. The limit of detection is 20-30 pmol, and the response of the fluorescence detection is linear up to 4 nmol. The separation of the aminooxy analogues from the naturally occurring polyamines can be varied by using different ketones for oxime formation. The method was used to measure the stability of aminooxy analogues of putrescine (1-aminooxy-3-aminopropane) and spermidine [N-(2 aminooxyethyl)-1,4-diaminobutane and 1-aminooxy-3-N-(3-aminopropyl)aminopropane] in cell culture media and the uptake into cultured baby hamster kidney (BHK21/C13) cells. PMID- 1629284 TI - High-performance liquid chromatographic determination of rifapentine in serum using column switching. AB - A high-performance liquid chromatographic method with column switching has been developed for the determination of rifapentine in serum. The serum samples were injected onto a precolumn packed with Corasil RP C18 (37-50 microns) after simple dilution with an internal standard in a 1% ascorbic acid solution. Polar serum components were washed out using 0.05 M phosphate buffer. After valve switching, the concentrated drugs were eluted in the back-flush mode and separated by a mu Bondapak C18 column with acetonitrile-tetrahydrofuran-0.05 M phosphate buffer (pH 7.0) (42:5:53, v/v/v) as the mobile phase. The method showed excellent precision with good sensitivity and speed, and a detection limit of 0.1 microgram/ml. The total analysis time was less than 25 min and the mean coefficients of variation for intra- and inter-assay were less than 4.8%. The method has been successfully applied to serum samples from dogs after the oral administration of rifapentine. PMID- 1629285 TI - Reversed-phase chromatography of phenylthiocarbamyl amino acid derivatives of physiological amino acids: an evaluation and a comparison with analysis by ion exchange chromatography. AB - Reversed-phase chromatography of phenylthiocarbamyl (PTC) amino acid derivatives of physiological amino acids was evaluated and compared with the traditional method of ion exchange. The PTC amino acid derivatives were stable for at least 32 h at ambient temperature before injection. The relationship of detector response to concentration for the PTC derivatives was linear from 39 to 1250 pmol. With few exceptions, the within- and between-run precisions of plasma amino acid retention times were less than 0.2 and 0.3%, respectively; the within- and between-run precisions of their concentrations were less than 4.0 and 5.0%, respectively. Twenty-four plasma samples were quantitated by both reversed-phase and ion-exchange chromatography; fifteen of the twenty amino acids determined had correlation coefficients in the range 0.81-1.00. Nine non-standard amino acids and ten therapeutic drugs were added to plasma; D-glucosaminic acid and alpha amino-beta-guanidinopropionic acid co-eluted with alpha-aminoadipic acid and threonine, respectively. Of the ten drugs added, only metronidazole and theophylline co-eluted with beta-alanine and histidine, respectively. The precision, stability, and sensitivity of the method render it ideal for the quantitation of plasma amino acids. PMID- 1629286 TI - Sensitive determination of cystathionine and assays for cystathionine beta- and gamma-lyase, as well as cystathionine beta-synthase, using high-performance liquid chromatography. AB - Cystathionine was cleaved into 2-ketobutyric acid, cysteine and ammonia by cystathionase. 2-Ketobutyric acid was converted into 3-ethyl-2-hydroxy-6,7 dimethoxyquinoxaline (EHDQ) by reaction with 1,2-diamino-4,5-dimethoxybenzene. When EHDQ was measured in a mobile phase of pH 2.1 using high-performance liquid chromatography with ultraviolet detection, 250 pmol of L-cystathionine in 250 microliters of the reaction mixture could be determined. Because EHDQ has a strong fluorescence in a mobile phase of pH 6.5 at 447 nm, on excitation at 365 nm, as little as 2.5 pmol of cystathionine in 250 microliters of the reaction mixture could be determined by high-performance liquid chromatography with fluorimetric detection. Cystathionase activity was assayed on the basis of the same principle by determining cystathionine in as little as 63 ng of rat liver by fluorimetric detection. Cystathionine beta-synthase activity was measured by the same method by determining cystathionine formed in only 113 ng of wet weight of rat liver. Using these methods, both cystathionine beta- and gamma-lyase activities in Saccharomyces cerevisiae were determined, because quinoxaline derivatives from pyruvate and 2-ketobutyrate could be measured simultaneously by high-performance liquid chromatography. PMID- 1629287 TI - Enzymatic shot-gun 5'-phosphorylation and 3'-sister phosphate exchange: a two dimensional thin-layer chromatographic technique to measure DNA deoxynucleotide modification. AB - DNA adducts occur through environmental, therapeutic, dietary, oxygen stress, and aging processes. A modified thin-layer chromatographic (TLC) technique can asses base composition and adduct formation. This requires labeling DNA by "shot-gun" 5'-phosphorylation of representative 32P-alpha-deoxyribonucleotide monophosphates. Subsequent 3'-monophosphate digest "sister exchanges" a radioactive 32PO4(2-) to the neighboring cold nucleotide. Separation in two dimensional polyethyleneimine-cellulose TLC is carried out in acetic acid, (NH4)2SO4, and (NH4)HSO4. The technique was applied to control DNA, cold substitution of dUMP, methylation, depurination, and pBR322. This technique quantifies low-molecular-mass adducts and DNA integrity both in vivo and in vitro. PMID- 1629288 TI - High-performance liquid chromatographic determination of spironolactone and its metabolites in human biological fluids after solid-phase extraction. AB - A simple and sensitive high-performance liquid chromatographic procedure to determine spironolactone and its three major metabolites in biological specimens is described. The assay involves sequential extraction on C18 and CN solid phases, and subsequent separation on a reversed-phase column. In plasma samples, spironolactone and its metabolites were completely separated within 8 min using an isocratic mobile phase, while in urine samples a methanol gradient was necessary to achieve a good separation within 14 min. Recoveries for all analytes were greater than 80% in plasma and 72% in urine. Linear responses were observed for all compounds in the range 6.25-400 ng/ml for plasma and 31.25-2000 ng/ml for urine. The plasma and urine methods were precise (coefficient of variation from 0.8 to 12.5%) and accurate (-12.1% to 7.4% of the nominal values) for all compounds. The assay proved to be suitable for the pharmacokinetic study of spironolactone in healthy human subjects. PMID- 1629289 TI - Studies on cyclic peptides related to gratisin by reversed-phase high-performance liquid chromatography. AB - The chromatographic behaviour of several synthetic peptides related to the antibiotic peptide gratisin was investigated using reversed-phase high performance liquid chromatography. The influence of the concentration of the peptides, column temperature and flow-rate on the chromatographic separation was examined. Of these peptides, some analogues with the D-X-D-Y-L-Pro or L-Pro-D-X-D Y sequences and strong activities gave double peaks in the chromatogram. The isomeric conformers were separated from each of the double peaks and were in equilibrium with each other at low temperatures. It is proposed that the presence of the sequences of D-X-D-Y-L-Pro and L-Pro-D-X-D-Y in these peptides gives rise to the stabilization and various degrees of hydrophobicity of their conformers. PMID- 1629290 TI - Determination of ethyl biscoumacetate and its metabolite 7-hydroxyethyl biscoumacetate in human serum by high-performance liquid chromatography and mass spectrometry. AB - An efficient reversed-phase high-performance liquid chromatographic method has been developed for the determination of ethyl biscoumacetate (EBA) and its metabolite in human serum, using the mu Bondapak C18 column and methanol-water phosphoric acid (56:46.8:0.2, v/v/v) as the mobile phase. This method permitted the determination of both EBA and a metabolite in human serum. The latter has been mentioned by other authors only in urine samples, where significant concentrations were found. Identification of the metabolite as 7-hydroxyethyl biscoumacetate was based on its chromatographic separation, followed by isolation from the eluate and direct mass spectrometric identification. It has been found that the higher EBA concentrations in human serum described by Brodie et al. [J. Pharmacol. Exp. Ther., 106 (1952) 453] were caused by the insufficient resolving power of the spectrophotometric method used, leading to overlapping of the UV spectra of the parent drug and its metabolite. PMID- 1629291 TI - Sensitive stereospecific assay of warfarin in plasma: reversed-phase high performance liquid chromatographic separation using diastereoisomeric esters of ( )-(1S,2R,4R)-endo-1,4,5,6,7,7-hexachlorobicyclo[2.2.1]-hept-5- ene-2-carboxylic acid. AB - A stereospecific reversed-phase high-performance liquid chromatographic (HPLC) assay for warfarin in plasma has been developed. The assay involves a rapid, simple clean-up procedure which separates warfarin from plasma constituents and warfarin metabolites. Warfarin enantiomers were assayed as their (-)-(1S,2R,4R) endo-1,4,5,6,7,7-hexachlorobicyclo[2.2.1]hept-5-ene -2- carboxylic acid diastereoisomeric esters by reversed-phase HPLC. Excellent resolution of the diastereoisomers was achieved in less than 10 min. Sensitivity of the assay was approximately 5-10 ng/ml for each isomer. PMID- 1629292 TI - Simultaneous direct determination of the enantiomers of verapamil and norverapamil in plasma using a derivatized amylose high-performance liquid chromatographic chiral stationary phase. AB - Chiralpak AD is a commercially available high-performance liquid chromatographic column containing a chiral stationary phase composed of 3,5 dimethylphenylcarbamate-derivatized amylose coated on silica. This column was applied to the assay for the plasma concentrations of the enantiomers of verapamil and its major metabolite norverapamil. After the extraction from plasma, the analytes were separated on a diol silica column (LiChrocart DIOL) and Chiralpak AD column which were connected in series in this order and detected using a fluorescence detector (excitation at 272 nm, emission at 317 nm). The enantiomers of verapamil and norverapamil were separated from each other and other metabolites using a mobile phase of hexane-isopropanol-ethanol (85:7.5:7.5, v/v/v) containing 1.0% triethylamine. The calibration curves were linear (R greater than 0.9989) in the plasma concentration range 2.5-100 ng/ml for verapamil enantiomers and 5.0-100 ng/ml for norverapamil enantiomers. The intra day and inter-day reproducibility tests showed good reproducibilities; coefficients of variation of each enantiomer were less than 14.9% at the lowest concentration and less than 2.0% at the highest concentration. The effect of organic modifier content and column temperature upon the retention and the enantioseparation were also discussed. PMID- 1629293 TI - High-performance liquid chromatographic assays for the quantification of amikacin in human plasma and urine. AB - Amikacin, an aminoglycoside antibiotic, is frequently coadministered with penicillins and broad-spectrum cephalosporins to synergize the activity of these agents. Sensitive, selective and reproducible high-performance liquid chromatographic assays have been developed for the quantification of amikacin in plasma and urine collected from human subjects. The plasma method involves the ultrafiltration of plasma prior to derivatization. An aliquot of plasma ultrafiltrate or urine is mixed with dimethyl sulfoxide and tris(hydroxymethyl)aminoethane followed by derivatization of amikacin with 1 fluoro-2,4-dinitrobenzene at 58 degrees C for 30 min. The reaction mixture is then injected directly onto a reversed-phase C18 column preceded by a guard column. The column is eluted with a mobile phase containing acetonitrile and 2 methoxyethanol in 1% Tris buffer. Amikacin derivative is detected at 340 nm. The methods were applied for the analysis of amikacin in plasma and urine samples from volunteers receiving amikacin and cefepime, a fourth-generation cephalosporin, in a clinical pharmacokinetic drug interaction study. PMID- 1629294 TI - Quantification of distinct molecular species of the 2-lyso metabolite of platelet activating factor by gas chromatography-negative-ion chemical ionization mass spectrometry. AB - The biological activity of platelet-activating factor (PAF) is comprised by a few molecular species of phosphatidylcholine which contain a fatty alcohol connected by an ether linkage to the sn-1 position of the glycerol backbone and an acetate ester at the sn-2 position. The various molecular species of PAF differ in chain length and degree of unsaturation in the fatty alcohol residue side-chain. PAF is rapidly hydrolyzed to lyso-PAF by an acetylhydrolase enzyme which is quite active in a number of cells that synthesize PAF. We describe a method for quantitation of lyso-PAF which involves conversion to its propionate derivative in the presence of an internal standard (deuterium-labelled PAF), digestion to the diglyceride with Bacillus cereus phospholipase C, conversion to the pentafluorobenzoate derivative and capillary column gas chromatographic-negative ion methane chemical ionization mass spectrometric analysis. Distinct molecular species of lyso-PAF can be individually quantitated at levels of 1 ng or less. These methods are applied to the demonstration of lyso-PAF accumulation in renal tissue from transplanted allografts undergoing acute rejection, in renal tissue from kidneys subjected to cold storage and autotransplantation, and in intestinal mucosa subjected to warm ischemia and reperfusion. PMID- 1629295 TI - Liquid chromatography-mass spectrometry of hydroxy and non-hydroxy fatty acids as amide derivatives. AB - A useful method for analyzing fatty acids by liquid chromatography-mass spectrometry with an atmospheric-pressure chemical-ionization interface system has been developed. The sensitivity of six kinds of palmitamide derivatives monitored by a single ion of [M+H]+ was, in decreasing order: N-n-propylamide greater than anilide greater than N,N-diethylamide, amide greater than N,N diphenylamide greater than N-1-naphthylamide. Individual fatty acids were identified from a mixture of amide derivatives of authentic fatty acids from C16:0 to C30:0 on a mass chromatogram. This method was used to detect both hydroxy and non-hydroxy fatty acids. Many kinds of fatty acid, including hydroxy fatty acids of the rat brain, were detected in a single run. PMID- 1629296 TI - High-performance liquid chromatography with electrochemical detection for the determination of levodopa, catecholamines and their metabolites in rat brain dialysates. AB - A high-performance liquid chromatographic assay with electrochemical detection is described for the simultaneous determination of levodopa, 3-O-methyldopa, dopamine, dihydroxyphenylacetic acid, homovanillic acid, 3-methoxytyramine, noradrenaline, adrenaline, 3-methoxy-4-hydroxyphenylethylene glycol and 5 hydroxyindoleacetic acid in rat brain dialysates. Samples are obtained in vivo using the microdialysis technique. Microdialysis probes are placed in the brain area to be studied and neurochemicals are collected by perfusion of the probe with modified Ringer's solution. Direct injection of the dialysates allows rapid and reliable results to be obtained. PMID- 1629297 TI - Analysis of proenkephalin A, proopiomelanocortin and protachykinin neuropeptides in human lumbar cerebrospinal fluid by reversed-phase high-performance liquid chromatography, radioimmunoassay and enzymolysis. AB - A comprehensive high-performance liquid chromatographic, radioimmunoassay, and enzymatic degradation scheme has been developed to analyze several intact neuropeptides and the corresponding peptides created by in vivo enzymolysis of precursors to study neuropeptides in human lumbar cerebrospinal fluid (CSF) and to test the hypothesis that defects in the metabolism (synthesis, degradation) of neuropeptide precursors, neuropeptides, and metabolites play a role in low back pain. CSF samples were obtained from three different patient groups: controls (C), whose low back pain was relieved without lidocaine; pharmacological responders (PR), whose pain was relieved by lidocaine and who were candidates for surgery; and pharmacological non-responders (PNR), whose pain was not relieved by lidocaine and a mid-thoracic anesthetic, and who were not candidates for surgery. The metabolic activity involved during synthesis and degradation of the peptides was assessed by measuring intact, native neuropeptide immunoreactivity in pre incubated and post-incubated CSF samples, where samples were incubated at 37 degrees C for 1 h. Pre-incubation radioimmunoassay measurements reflected the content of intact peptides present in lumbar CSF at the time of sampling, and post-incubation measurements assayed the amount of peptide that had remained embedded within its precursors [cryptic methionine enkephalin (ME)] and that had been released by the action of CSF peptidases. Significant differences were found in post-incubation samples for the amount of proenkephalin A [ME, leucine enkephalin (LE)] and tachykinin [substance P (SP)] peptides. For example, significant differences were observed for ME-like immunoreactivity (C versus cryptic), SP-like immunoreactivity (PNR versus PR), and LE-like immunoreactivity (PR versus C). No significant differences were observed among the peptides within the pre-incubation samples.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629298 TI - Coupling of m-aminophenylboronic acid to s-triazine-activated Sephacryl: use in the affinity chromatography of glycated hemoglobins. AB - An improved process is described for covalent coupling of m-aminobenzeneboric acid to s-triazine-activated Sephacryl matrices. The derivatized Sephacryl gel contained up to 150-200 mumol boronate per ml. It has been applied to the separation of glycated and non-glycated hemoglobins (Hbs) present in red-cell hemolysate. The new bioaffinity support was evaluated by the analysis of 67 diabetic patients and 20 normal adults. The mean value for glycated Hb was 6.6 +/ 0.8% for non-diabetics and 11.2 +/- 2.9% for diabetics. The method effects group specific separation between glycated and non-glycated Hbs even in presence of foetal Hb and abnormal Hb variants. There is an excellent correlation between the glycated Hb levels obtained by the new method and two established procedures, namely high-performance liquid chromatography (r = 0.933) and affinity Merckotest (r = 0.991). The inter-assay and intra-assay coefficient of variations of less than 3.0% suggest that the method is reproducible. The results indicate that the method may serve as an alternative procedure for the study of glycated proteins. The s-triazine-activated Sephacryl could also be used for immobilizing enzymes and for preparing biospecific absorbents. PMID- 1629299 TI - Liquid chromatographic monitoring of pseudocholinesterase activity: comparison of methods. AB - In order to study the activity of pseudocholinesterase in vitro, two liquid chromatographic techniques have been developed. One is based on phase transfer catalyzed (PTC) esterification of the carboxylic acid formed during hydrolysis of the substrate, and the other on the use of a radioisotopically labeled substrate. In both cases, the substrate used was a long-chain choline ester. The PTC method, utilizing (N-9-acridinyl)bromoacetamide as a fluorogenic labeling reagent in an aqueous-organic two-phase system, gives esters with very high fluorescence intensity. The radiochromatographic method makes use of on-line radioactivity monitoring of the substrate and product in order to follow the hydrolysis reaction. In both methods reversed-phase liquid chromatography is used. A method for the synthesis of 3H-labeled choline esters is also described. Both techniques are compared with regard to sensitivity, reproducibility and practical considerations. PMID- 1629300 TI - Determination of concentrations of adenosine and other purines in human term placenta by reversed-phase high-performance liquid chromatography with photodiode array detection: evidence for pathways of purine metabolism in the placenta. AB - A robust analytical method, using reversed-phase high-performance liquid chromatography with gradient elution and photodiode-array detection, was used to measure six purines and beta-NAD+ in acid-soluble extracts of samples taken from six different regions of human term placenta. Resolution of the analyte peaks in chromatographic profiles of the extracts, and the use of optimized integration, allowed simultaneous quantitation of all seven analytes from a single chromatogram. Peak purity was confirmed via on-line analysis of peak spectra, utilizing the purity parameter treatment of spectral data. Major placental purines were adenosine, inosine, hypoxanthine and adenine. Except for adenine, concentrations of the purines varied by two-fold or more between different regions of each placenta, but concentration ratios, i.e., adenosine/inosine and inosine/hypoxanthine, were similar. The findings indicate that the pathway of ATP breakdown to hypoxanthine in ischemic human term placenta is via adenosine, and that regional differences in placental concentrations of adenosine and its metabolites may result from regional differences in degree of ischemia. PMID- 1629301 TI - Direct determination of the enantiomeric ratio of verapamil, its major metabolite norverapamil and gallopamil in plasma by chiral high-performance liquid chromatography. AB - Two methods for the determination of the enantiomeric ratio of verapamil in plasma by high-performance liquid chromatography have been developed. On an alpha 1-acid glycoprotein chiral stationary phase (Chiral-AGP) verapamil was separated after the acetylation of the main metabolite norverapamil, which interferes with the resolution of verapamil. On an amylose tris-3,5-dimethylphenylcarbamate column (Chiralpak AD) verapamil and norverapamil were determined simultaneously without prior derivatization. Gallopamil was separated on both columns under similar conditions. PMID- 1629302 TI - Simultaneous determination of nefiracetam and its metabolites by high-performance liquid chromatography. AB - A reversed-phase high-performance liquid chromatographic assay was developed to simultaneously quantitate nefiracetam (NEF), a novel nootropic agent, and its three known oxidized metabolites (N-[(2,6 dimethylphenylcarbamoyl)methyl]succinamic acid (5-COOH-NEF), 4-hydroxy-NEF and 5 hydroxy-NEF) in human serum and urine. The quantitative procedure was based on solid-phase extraction with Sep-Pak C18 and ultraviolet detection at 210 nm. The calibration curves of NEF and the metabolites were linear over a wide range of concentrations (0.5-21.5 nmol/ml for NEF and 0.4-9.5 nmol/ml for metabolites in serum and 4-86 nmol/ml for NEF and 8-190 nmol/ml for metabolites in urine). Intra and inter-day assay coefficients of variation for the compounds were less than 10%. The limit of detection was 0.1 nmol/ml for NEF, 5-COOH-NEF and 4-hydroxy NEF, and 0.2 nmol/ml for 5-hydroxy-NEF in both serum and urine. This method is applicable for the determination of NEF and its metabolites in human serum and urine with satisfactory accuracy and precision. PMID- 1629303 TI - Simultaneous determination of furosemide and amiloride in plasma using high performance liquid chromatography with fluorescence detection. AB - A high-performance liquid chromatographic method using fluorescence detection for the simultaneous determination of furosemide and amiloride is described. The chromatographic system is based on reversed-phase ion-pair chromatography with sodium dodecylsulphate as ion-pairing agent. The same counter-ion is used for the ion-pair liquid-liquid extraction to ethyl acetate. The minimum detectable concentration amounts to 0.3 ng of furosemide and 0.03 ng of amiloride per ml of plasma. The applicability of the method is demonstrated by the analysis of plasma samples taken from volunteers receiving both drugs. PMID- 1629304 TI - Simultaneous determination of the camptothecin analogue CPT-11 and its active metabolite SN-38 by high-performance liquid chromatography: application to plasma pharmacokinetic studies in cancer patients. AB - CPT-11 (I; 7-ethyl-10-[4-(1-piperidino)-1- piperidino]carbonyloxycamptothecin) is a new anticancer agent currently under clinical development. A sensitive high performance liquid chromatographic assay suitable for the simultaneous determination of I and its active metabolite SN-38 (II) in human plasma, and their preliminary clinical pharmacokinetics, are described. Plasma samples were processed using a solid-phase (C18) extraction step allowing mean recoveries of I, II and the internal standard camptothecin (III) of 84, 99 and 72%, respectively. The extracts were chromatographed on a C18 reversed-phase column with a mobile phase composed of acetonitrile, phosphate buffer and heptanesulphonic acid, with fluorescence detection. The calibration graphs were linear over a wide range of concentrations (1 ng/ml-10 micrograms/ml), and the lower limit of determination was 1 ng/ml for both I and II. The method showed good precision: the within-day relative standard deviation (R.S.D.) (5-1000 ng/ml) was 13.0% (range 4.9-19.4%) for I and 12.8% (6.7-19.1%) for II; the between-day R.S.D. (5-10,000 ng/ml was 7.9% (5.4-17.5%) for I and 9.7% (3.5 15.1%) for II. Using this assay, plasma pharmacokinetics of both I and II were simultaneously determined in three patients receiving 100 mg/m2 I as a 30-min intravenous infusion. The mean peak plasma concentration of I at the end of the intravenous infusion was 2400 +/- 285 ng/ml (mean +/- standard error of the mean). Plasma decay was triphasic with half-lives alpha, beta and gamma of 5.4 +/ 1.8 min, 2.5 +/- 0.5 h and 20.2 +/- 4.6 h, respectively. The volume of distribution at steady state was 105 +/- 15 l/m2, and the total body clearance was 12.5 +/- 1.9 l/h.m2. The maximum concentrations of the active metabolite II reached 36 +/- 11 ng/ml. PMID- 1629305 TI - Diagnosis of disseminated candidiasis based on serum D/L-arabinitol ratios using negative chemical ionization mass spectrometry. AB - The main objective was to appraise the diagnostic specificity of the serum D/L arabinitol ratio technique in a patient population biased for renal dysfunction. The D/L ratio (mean +/- S.D.) in normal serum (n = 29) was 1.76 +/- 0.47 (range 0.77-2.75). D/L-Arabinitol greater than 3.18 (mean + 3 S.D.) are considered indicative of disseminated candidiasis. Of 49 patients without candidiasis, but 46% with serum creatinine greater than 1.5 mg/dl, diagnostic specificity was 88%. In confirmed candidiasis (n = 16) sensitivity was 94% (D/L range 3.2-50.1). Switching from positive to negative chemical ionization permits the use of as little as 5 microliters sample (20 microliters used routinely; D/L ratios constant in the 5-200 microliters range) permitting the extension of the technique to pediatric applications. Results can obtained in 2 h. Suggested areas of clinical application include aiding diagnosis, monitoring patients as risk so that treatment could be initiated while fungus load is still small, and following the course of antifungal chemotherapy. PMID- 1629306 TI - Artifact formation during gas chromatographic-mass spectrometric analysis of a methylsulfinyl-containing metabolite. AB - During gas chromatographic-mass spectrometric analysis using a heated injector, 1 methylthio-4-methylsulfinyltetrachlorobenzene degraded to form tetrachlorothioanisole. Similar reductive defunctionalizations have been reported during in vivo metabolisms. Caution should be used to distinguish metabolites from artifacts which may be formed during the analysis of methylsulfoxides. PMID- 1629307 TI - Identification and quantification of ergotamine in human plasma by gas chromatography-mass spectrometry. AB - A highly sensitive and simple gas chromatographic-mass spectrometric method is described for the identification and quantification of ergotamine in plasma or serum. Ergotamine is extracted with chloroform from the alkalinized sample and detected by electron ionization mass spectrometry. This analytical method was selected for an intense high-mass ion ideal for the specific quantification. It shows good linearity in the range from 50 pg/ml to 50 ng/ml for ergotamine in plasma. The practicability of this method is demonstrated by determining the plasma concentration of ergotamine in a sample from a patient. PMID- 1629308 TI - Identification of new urinary metabolites of trimeprazine in rats by gas chromatography-mass spectrometry. AB - The metabolites of trimeprazine were identified in urine of rats by gas chromatography-mass spectrometry. After the oral administration of trimeprazine, the urinary metabolites were extracted with diethyl ether before or after hydrolysis with beta-glucuronidase. The identified metabolites were N demethyltrimeprazine,3-hydroxytrimeprazine,N-demethyl-3-++ +hydroxytrimeprazine and trimeprazine sulphoxide. PMID- 1629309 TI - Measurement of trazodone in plasma and brain of rat by capillary gas chromatography with a nitrogen-selective detector. AB - A specific and highly sensitive method for the measurement of trazodone in plasma and brain of rat is presented. The compound and the internal standard were extracted from alkalinized samples with hexane and analysed by capillary gas chromatography with nitrogen-selective detection. The method was demonstrated to be accurate and precise. The limits of determination were 2 ng/ml for plasma and 24 ng/g for brain, which makes this procedure suitable for pharmacokinetic analysis. PMID- 1629310 TI - Plasma determination of the novel anticonvulsant D,L-3-hydroxy-3-ethyl-3 phenylpropionamide and preliminary pharmacokinetic studies in the rat. AB - A sensitive gas chromatographic method with flame ionization detection was developed for the analysis in plasma of the novel anticonvulsant D,L-3-hydroxy-3 ethyl-3-phenylpropionamide (HEPP), using D,L-2-hydroxy-2-ethyl-2-phenylacetamide as the internal standard. HEPP was extracted from alkalinized plasma into dichloromethane and quantified after derivatization with bis(trimethylsilyl) trifluoroacetamide: Standard curves were linear from 0.5 to 50 and from 2 to 100 micrograms/ml of plasma, using 1.5 and 5 micrograms of the internal standard, respectively. The lower limit of detection at a signal-to-noise ratio of 3 standard deviations was 0.33 micrograms/ml of sample. The sensitivity, accuracy and reproducibility of the method were shown to be satisfactory for pharmacokinetic studies of HEPP. After intraperitoneal administration of 50 mg/kg to Wistar rats, the principal kinetic parameters were: absorption half-life = 0.04 h; volume of distribution = 1.32 l/kg; clearance = 4.40 ml/min; peak concentration = 50 micrograms/ml; peak time = 0.25 h; mean residence time = 4.55 h. PMID- 1629311 TI - Simultaneous determination of caffeine and its primary demethylated metabolites in human plasma by high-performance liquid chromatography. AB - An improved high-performance liquid chromatographic method for the simultaneous determination of caffeine and its three primary metabolites (theophylline, theobromine and paraxanthine) in human plasma is described. The four substances were separated on a reversed-phase column (5 microns TSK gel ODS-80TM, 150 mm x 4.6 mm I.D.) by use of the mobile phase methanol-0.1 M NaH2PO4 (30:70, v/v) with a flow-rate of 0.8 ml/min. Absorbance was monitored at 274 nm. The detection limit was 5 ng/ml for theobromine and caffeine and 10 ng/ml for paraxanthine and theophylline. The linearity and reproducibility were sufficient for drug monitoring of caffeine and its primary methylxanthines. PMID- 1629312 TI - Determination of the enantiomers of a novel 20,21-dinoreburnamenine derivative in rat plasma and brain by high-performance liquid chromatography using a chiral stationary phase. AB - A high-performance liquid chromatographic method with solid-phase extraction was developed for the assay of the enantiomers of a novel 20,21-dinoreburnamenine derivative (RU 49041) in rat plasma and brain using a chiral stationary phase (Nucleosil Chiral 2) and ultraviolet detection. The limit of detection was 10 ng/ml (or ng/g) in both tissues and the intra-assay precision was satisfactory (plasma, ca. 5%; brain, ca. 1%). The pharmacokinetic profiles of the two enantiomers were determined following oral administration of the racemate (10 mg/kg). The results show that their pharmacokinetics are very different: whereas both enantiomers appear in the brain, only the 3 alpha,16 beta-enantiomer is detected in plasma. PMID- 1629313 TI - Determination of the novel hydroxymethyl glutaryl coenzyme A reductase inhibitor (RP 61969) and its dihydroxy acid hydrolysis product in human plasma by reversed phase high-performance liquid chromatography. AB - A method is described for the determination of the novel hydroxymethyl glutaryl coenzyme A reductase inhibitor RP 61969 (I) and its hydrolysis product, the dihydroxy acid RP 62420 (II), in human plasma. A structural isomer of I is used as internal standard. Both I and II were extracted from acidified plasma with diethyl ether. The dried residues were reconstituted in the high-performance liquid chromatography mobile phase and chromatographed on a 5 microns ODS2 column. The mobile phase used was aqueous dipotassium phosphate +tetra-n-butyl ammonium bromide (both 10 mM)-acetonitrile-methanol (60:40:5, v/v). At a flow rate of 1.5 ml min-1 and ambient temperature, the retention time of II is 3.5 min, that of the internal standard is 5 min, and that of I is 8 min. The method has been validated and applied to the assay of plasma samples resulting from a cell-plasma distribution experiment in human whole blood. PMID- 1629314 TI - Comparison of a novel thin-layer chromatographic-fluorescence detection method with a spectrofluorometric method for the determination of 7-hydroxycoumarin in human urine. AB - A novel method for the determination of 7-hydroxycoumarin in human urine which combines thin-layer chromatography (TLC) with fluorescence detection (FD) has been devised. The limit of detection (1 ng/ml) enables determination of 7 hydroxycoumarin after both administration of coumarin and environmental exposure to this fragrance material. When compared to a spectrofluorometric method of analysis, the TLC-FD method proved to be more selective for the analysis of 7 hydroxycoumarin in human urine. PMID- 1629315 TI - Detection of vancomycin resistance in Enterococcus species. AB - Enterococcus faecalis and Enterococcus faecium isolates that are resistant to vancomycin have recently been identified in North America and Europe. Of 155 clinical isolates of enterococci (113 E. faecium and 42 E. faecalis), we found that 98 were resistant, 52 were moderately susceptible, and 5 had intermediate susceptibilities to vancomycin by using broth microdilution susceptibility testing according to the National Committee for Clinical Laboratory Standards (NCCLS) (Approved Standard M7-A2). Using NCCLS disk diffusion methodology (Approved Standard M2-A4), we evaluated the NCCLS supplemental M100-S3 revisions for zone diameter interpretive standards and incubation conditions and found 5.8% minor errors. A total of 234 isolates, which included an additional 79 E. faecium isolates that were moderately susceptible to vancomycin, were used to evaluate the Vitek GPS-TA card (bioMerieux, Inc., Hazelwood, Mo.) and the Pos MIC type 6 panel (MicroScan; Baxter Health Care Corp., West Sacramento, Calif.) for the detection of vancomycin resistance. The Vitek card was 100% specific and 72% sensitive, whereas the MicroScan panel with the Walk/Away system was 98% specific, with a sensitivity of 93% which increased to 99% when readings were performed manually. An agar screen plate method was evaluated with vancomycin concentrations of 6, 8, 10, or 12 micrograms/ml; plates were inoculated so as to obtain a final concentration of 10(5) CFU per spot. This method was found to be 100% sensitive and specific at all concentrations. PMID- 1629316 TI - Efficient culture of Chlamydia pneumoniae with cell lines derived from the human respiratory tract. AB - Two established cell lines, H 292 and HEp-2, originating from the human respiratory tract, were found to be significantly more efficient and practical than the currently used HeLa 229 cells for growth of Chlamydia pneumoniae. Six strains of C. pneumoniae recently isolated from patients with respiratory ailments were used as test cultures. The H 292 and HEp-2 cells yielded much higher inclusion counts for all the test strains than did HeLa 229 cells. When they were compared with each other, H 292 cells yielded more inclusions than did HEp-2 cells, and the differences were statistically significant in 10 of 18 test sets. A simple system with these two cell lines appeared to be very efficient for culturing C. pneumoniae. It does not require treatment of tissue cells with DEAE dextran before infection, and it may eliminate the need for serial subpassages of specimens to increase culture sensitivity. Monolayers of these cells remained intact and viable in the Chlamydia growth medium so that reinfection could take place, resulting in greatly increased inclusion counts for specimens containing few infectious units. This system may make it more practical for laboratories to culture for C. pneumoniae for treatment of infections and outbreak intervention and will facilitate studies on this recently recognized pathogen. PMID- 1629317 TI - Antibodies to shiga holotoxin and to two synthetic peptides of the B subunit in sera of patients with Shigella dysenteriae 1 dysentery. AB - Acute- and convalescent-phase sera from 18 Thai patients and convalescent-phase sera from two Israeli patients and one Bangladeshi patient with Shigella dysenteriae 1 (Shiga) dysentery were tested by enzyme-linked immunosorbent assay to detect antibodies that bind S. dysenteriae lipopolysaccharide (LPS), Shiga holotoxin, or two synthetic peptides representing epitopes from the B subunit of Shiga toxin. Paired sera from 24 Maryland adults with Shigella flexneri 2a or Shigella sonnei diarrhea served as negative controls. Of the 16 paired Thai serum samples tested for immunoglobulin G LPS antibody, 10 had greater than or equal to 4-fold rises (the two subjects with the highest convalescent-phase titers exhibited toxin-neutralizing activity); acute-phase specimens from four of the remaining six individuals already had elevated Shiga LPS titers in their acute specimens ranging from 1:800 to 1:12,800. Similarly, convalescent-phase sera from the two Israeli patients and the Bangladeshi patient revealed LPS titers of 1:800 to 1:3,200. In contrast, none of the Maryland volunteers with S. flexneri or S. sonnei diarrhea manifested rises in Shiga anti-LPS (P less than 0.00001 versus 10 of 16 Thai patients). Only 4 of the 18 Thai patients had significant rise in antibody to purified Shiga toxin, while one of the two Israeli patients and the one Bangladeshi patient had elevated convalescent-phase titers. None of the sera that reacted with Shiga holotoxin had antibody that bound to the peptides. This report, which describes a search for serum antibodies that bind Shiga toxin in patients with Shiga dysentery, demonstrates such antibodies in only a minority of patients with bacteriologically confirmed disease. During Shiga dysentery, Shiga toxin may be elaborated in such small quantities in vivo that it fails to elicit an immune response in most patients even though it may exert biological effects. In this behavior Shiga toxin resembles tetanus toxin, another potent exotoxin that fails to elicit antitoxic responses in people who recover from clinical tetanus. PMID- 1629318 TI - Detection of Borrelia burgdorferi DNA in urine samples and cerebrospinal fluid samples from patients with early and late Lyme neuroborreliosis by polymerase chain reaction. AB - A polymerase chain reaction (PCR) was developed for use in the identification of a 248-bp fragment of the Borrelia burgdorferi flagellin gene in urine and cerebrospinal fluid (CSF) from patients with Lyme neuroborreliosis. The specificities of the PCR products were confirmed by DNA-DNA hybridization with an internal probe. The assay had a detection limit of 10 in vitro-cultivated B. burgdorferi. The PCR assay seemed to be species wide as well as species specific, since DNA from all 21 B. burgdorferi isolates from humans tested but not from Borrelia hermsii or Treponema pallidum could be amplified. We tested 10 consecutively diagnosed patients with untreated neuroborreliosis. There was lymphocytic pleocytosis and intrathecal B. burgdorferi-specific antibody synthesis in the CSF of all patients. Urine and CSF samples were investigated by PCR before, during, and up to 8.5 months after therapy. B. burgdorferi DNA was detected in urine samples from nine patients; five patients, including two patients with chronic neuroborreliosis, were PCR positive prior to treatment, whereas urine samples from the remaining four patients obtained 3 to 6 days after the onset of therapy became PCR positive. All urine samples obtained greater than 4 weeks after therapy were negative by PCR. PCR of CSF was less sensitive, and samples from only four patients, including one with chronic neuroborreliosis, were positive. We conclude that urine is a more suitable sample source than CSF for use in B. burgdorferi DNA detection by PCR. Normalization of inflammatory CSF changes and the negative PCR results during follow-up even in patients with chronic neuroborreliosis do not point to a persistent infection. The future role of PCR as a diagnostic tool for Lyme neuroborreliosis is still uncertain. PMID- 1629319 TI - Detection of Staphylococcus aureus by polymerase chain reaction amplification of the nuc gene. AB - Synthetic oligonucleotide primers of 21 and 24 bases, respectively, were used in the polymerase chain reaction (PCR) to amplify a sequence of the nuc gene, which encodes the thermostable nuclease of Staphylococcus aureus. A DNA fragment of approximately 270 bp was amplified from lysed S. aureus cells or isolated DNA. The PCR product was detected by agarose gel electrophoresis or Southern blot analysis by using a 33-mer internal nuc gene hybridization probe. With S. aureus cells the lower detection limit was less than 10 CFU, and with the isolated target the lower detection limit was 0.69 pg of DNA. The primers recognized 90 of 90 reference or clinical S. aureus strains. Amplification was not recorded when 80 strains representing 16 other staphylococcal species were tested or when 20 strains representing 9 different nonstaphylococcal species were tested. Some of the non-S. aureus staphylococci produced thermostable nucleases but were PCR negative. The PCR product was generated when in vitro-cultured S. aureus was used to prepare simulated clinical specimens of blood, urine, cerebrospinal fluid, or synovial fluid. No PCR product was generated when the sterile body fluids were tested. However, the sensitivity of the PCR was reduced when S. aureus in blood or urine was tested in comparison with that when bacteria in saline were tested. With the bacteria in blood, the detection limit of the PCR was 10(3) CFU. A positive PCR result was recorded when a limited number of clinical samples from wounds verified to be infected with S. aureus were tested, while the PCR product was not detected in materials from infections caused by other bacteria. Generation of PCR products was not affected by exposure of S. aureus to bactericidal agents, including cloxacillin and gentamicin, prior to testing, but was affected by exposure to UV radiation. The PCR for amplification of the nuc gene has potential for the rapid diagnosis of S. aureus infections by direct testing of clinical specimens, including specimens from patients with ongoing antimicrobial therapy. PMID- 1629320 TI - Investigation of ampicillin-intermediate strains of Haemophilus influenzae by using the disk diffusion procedure and current National Committee for Clinical Laboratory Standards guidelines. AB - It was noted in our laboratory that certain strains of Haemophilus influenzae yielded zone sizes interpreted as resistant to the ampicillin (AMP) disk on chocolate-Mueller-Hinton agar (CMH) but showed no evidence of beta-lactamase (beta-Lac) activity. Although it is known that a second mechanism of AMP resistance exists, strains with this mechanism are uncommon. To investigate this apparent discrepancy, a study of 100 consecutive clinical isolates of H. influenzae collected over a 6-month period was performed. Isolates were simultaneously tested against five antibiotics (AMP, chloramphenicol, cefotaxime, ciprofloxacin, and AMP-sulbactam) on CMH and on two brands of Haemophilus test medium (HTM) by using the disk diffusion procedure and National Committee for Clinical Laboratory Standards (NCCLS) standards. By using CMH and NCCLS standard M2-A3-S2, strains of H. influenzae showing zone sizes of greater than or equal to 20 mm with AMP were considered sensitive. By using HTM and NCCLS standard M2-A4, strains showing zone sizes of greater than or equal to 25 mm to AMP on HTM were considered sensitive. Intermediate strains had zone sizes of 22 to 24 mm. The majority of isolates (68%) were sensitive to all antibiotics. Two percent of the isolates were resistant to chloramphenicol. Seventeen percent of the isolates were AMP-resistant, beta-Lac-producing strains of H. influenzae. Thirteen percent of the isolates gave at least one intermediate or resistant zone for AMP but were beta-Lac negative. MIC determinations with NCCLS standard M7-A2 were performed with resistant and intermediate strains. MICs for beta-Lac-producing strains of H. influenzae were >/= 8.0 microgram/ml. MICs for beta-Lac-negative strains were 4 microgram/ml; 31 of the 33 staphylococcal isolates were determined by ED-PCR to be mecA gene positive. These results suggest that ED-PCR can be used with reasonable confidence in the clinical microbiological laboratory. PMID- 1629329 TI - Reliability of a bioluminescence ATP assay for detection of bacteria. AB - The reliability of bioluminescence assays which employ the luciferin-luciferase ATP-dependent reaction to evaluate bacterial counts was studied, both in vitro and on urine specimens. Bioluminescence and cultural results for the most common urinary tract pathogens were analyzed. Furthermore, the influence of the culture medium, of the assaying method, and of the phase of growth on bioluminescence readings was studied. Results show that Proteus, Providencia, and Morganella strains are not correctly detected, neither in vitro nor in urine samples, by the standard assaying method. The analysis of assaying parameters demonstrated that some modifications to the extraction procedure of bacterial ATP could improve the reliability of this technique. PMID- 1629330 TI - Immunoglobulin G antibodies to Helicobacter pylori in patients with dyspeptic symptoms investigated by the western immunoblot technique. AB - Helicobacter pylori is a gram-negative, curved, rod-shaped bacterium known to cause gastritis and to be an important factor in the pathogenesis of peptic ulcers. Serological testing has recently been proposed as an aid in diagnosis of H. pylori infections. In this study, we used the Western immunoblot technique to evaluate the possibility of using one or more of the antigens from H. pylori for this purpose. Thirteen major bands and about 30 minor bands could be identified by Western blotting when sera from 53 consecutive dyspeptic patients, 27 healthy children, and 25 blood donors were evaluated. Antibodies against most of the major bands were found significantly more frequently in patients with H. pylori infections than in patients without such infections. However, antibodies against a single polypeptide were not produced by all patients with H. pylori infection. Polypeptides with molecular masses of 120, 50, and between 19 and 36 kDa seem to be the most specific polypeptides for the diagnosis of H. pylori infections. This study showed only minor differences in antigenic composition between different clinical isolates of H. pylori, and serological cross-reactions with other bacteria were limited. Major serological cross-reactions were found only with Campylobacter jejuni and with bacterial lipopolysaccharide. However, one band at 60 kDa reacted with antiserum to the Legionella micdadei common antigen, which may indicate a cross-reaction with common antigen from several other bacteria. This study demonstrates that a number of bands may be useful as antigens in serological tests after isolation and purification. PMID- 1629331 TI - Absolute quantitation of viremia in human immunodeficiency virus infection by competitive reverse transcription and polymerase chain reaction. AB - A competitive polymerase chain reaction (PCR)-based assay for the quantitative detection of human immunodeficiency virus type 1 (HIV-1) viremia was developed and optimized. This method consists of the reverse transcription and subsequent amplification in the same tube of two similar RNA templates, the wild-type template to be quantified and a known amount of the internally deleted synthetic template, both with identical primer recognition sites. The same strategy also proved to be useful in the quantitative assay of HIV-1-specific cellular transcripts and proviral DNA sequences from peripheral blood mononuclear cells by using competitor DNA. The method might be of interest in the study of the precise level of HIV-1 activity during the different clinical phases of the infection and in the simple, fast, and methodologically correct molecular investigation of patients treated with specific antiviral compounds. PMID- 1629332 TI - Typhus and typhuslike rickettsiae associated with opossums and their fleas in Los Angeles County, California. AB - The recent discovery of cat fleas (Ctenocephalides felis) infected with a typhuslike rickettsia (designated the ELB agent) raises the question of whether similar rickettsial infections exist in wild cat flea populations. We verified the presence of the ELB agent and Rickettsia typhi in urban and suburban areas of Los Angeles, Calif. Opossums trapped in close proximity to the residences of human murine typhus cases in Los Angeles county and other areas within the city of Los Angeles were tested for the presence of typhus group rickettsiae by the polymerase chain reaction (PCR). The presence of rickettsiae in the spleen tissues of three opossums (n = 9) and in 66 opossum fleas (n = 205) was determined by PCR and was verified by dot blot and Southern transfer hybridization. Further analysis of the amplified PCR products generated by a series of primer pairs derived from either the 17-kDa antigen gene or the citrate synthase gene revealed that both R. typhi and the ELB agent were present in the tested samples. Dual infection was not noted in the samples; however, the fleas were infected with either R. typhi or the ELB agent. The presence of the ELB agent in the cat flea population may have implications for public health. Whether this agent is responsible for the mild cases of human murine typhus in urban and suburban areas of Los Angeles or in other endemic foci remains to be determined. PMID- 1629333 TI - Human immunodeficiency virus type 1 is present in the cerebrospinal fluid of a majority of infected individuals. AB - Cerebrospinal fluid (CSF) specimens from 63 patients with different severities of human immunodeficiency virus (HIV-1) infection, including asymptomatic virus carriers, were examined for the presence of HIV-1 by using polymerase chain reaction (PCR) and virus isolation. Polyadenylated RNA, presumably associated with virus particles, was extracted and reverse transcribed, and the pol region was amplified in a nested PCR. Virus could be detected in 90% of the CSF specimens examined by PCR, and data on isolation of virus from CSF were in agreement with these figures. In fact, when several CSF specimens from the same individual were studied, HIV-1 could be isolated from 80% of the patients. The presence of the viral RNA in CSF was independent of the clinical stage of infection and of neurological symptoms. These results show that the spread of HIV 1 to the brain represents an early event during infection and occurs in the majority of asymptomatic individuals. PMID- 1629334 TI - Secondary immune response in a vaccinated population during a large measles epidemic. AB - The rates of secondary immune response (SIR) and secondary vaccine failure (SVF) during a measles epidemic (10,184 notifications) were evaluated. A patient with SIR was defined as a subject for whom all sera were immunoglobulin G (IgG) positive and IgM negative with a significant increase in complement fixation titer. A patient with SVF was defined as a vaccinated symptomatic subject showing a SIR. Sequential sera from 898 subjects were tested for measles antibody by enzyme-linked immunosorbent assay (IgG and IgM) and by complement fixation. Evidence of recent anti-measles virus specific immune response was found in 496 subjects (55.5%). The vaccination rate was estimated at 74.6% (99% confidence interval [CI], 67.9 to 80.7%). The number of exposed vaccinated subjects was estimated at 370 (74.6% of 496). The SIR rate was 4.03% (20 of 496) (99% CI, 2.1 to 6.9%) among subjects with immune response. These 20 subjects were 2 with measles (Centers for Disease Control's definition), 6 with measles with rash of unknown duration, 8 with presumed measles with either rash or fever, 3 asymptomatic subjects (2 with recent contact with a measles case), and 1 undocumented subject. Since 3 patients with SIR were asymptomatic and 2 others were documented as not vaccinated, there was a maximum of 15 probable occurrences of SVF among the 20 patients with SIR. The SVF rate among exposed vaccinated subjects was estimated at 4.05% (15 of 370) (99% CI, 1.9 to 7.5%). In conclusion, neither prior vaccination nor detectable SIR ensures protective immunity. Measles virus may induce asymptomatic SIR in IgG-seropositive subjects. SVF led to typical or modified measles but did not seem to have played an important role during this epidemic. PMID- 1629335 TI - Evaluation of the bead enzyme-linked immunosorbent assay for detection of cholera toxin directly from stool specimens. AB - A highly sensitive bead enzyme-linked immunosorbent assay (bead ELISA) for detection of cholera toxin (CT) was evaluated for direct detection of CT from stool specimens of patients with acute secretory diarrhea. Of the 75 stool samples examined, 59 yielded biochemically, and serologically confirmed strains of Vibrio cholerae O1. The bead ELISA was positive for CT in stool supernatants in 50 (84.7%) of the 59 samples from which V. cholerae O1 was isolated. In addition, the bead ELISA was positive for three stool specimens which were negative by culture. The free CT present in 48 of the 50 stool samples positive by culture for V. cholerae O1 and for CT by bead ELISA was completely absorbed by anti-CT immunoglobulin G. All of the 59 strains of V. cholerae O1 biotype eltor isolated in this study produced in vitro CT. The concentration of CT present in the bead ELISA-positive stool samples ranged between 26 pg/ml and greater than 100 ng/ml. This evaluation study demonstrates that the bead ELISA is a sensitive and simple method for direct detection of CT in nonsterile stool samples, and we recommend routine use of this assay for detection of CT in stool samples and culture supernatants in clinical and reference laboratories. PMID- 1629336 TI - Standardization of sensitive human immunodeficiency virus coculture procedures and establishment of a multicenter quality assurance program for the AIDS Clinical Trials Group. The NIH/NIAID/DAIDS/ACTG Virology Laboratories. AB - An independent quality assurance program has been established by the Division of AIDS, National Institute of Allergy and Infectious Diseases, for monitoring virologic assays performed by nearly 40 laboratories participating in multicenter clinical trials in the United States. Since virologic endpoints are important in evaluating the timing and efficacy of therapeutic interventions, it is imperative that virologic measurements be accurate and uniform. When the quality assurance program was initially created, fewer than 40% of the laboratories could consistently recover human immunodeficiency virus (HIV) from peripheral blood mononuclear cells (PBMCs) of HIV-infected patients. By comparing coculture procedures in the more competent laboratories with those in laboratories who were struggling to isolate virus, optimal conditions were established and nonessential reagents and practices were eliminated. Changes were rapidly introduced into a laboratory when experience dictated that such modifications would result in a favorable outcome. Isolation of HIV was enhanced by optimizing the numbers and ratios of patient and donor cells used in cultures, by standardizing PBMC separation procedures, by using fresh rather than frozen donor PBMCs, by processing whole blood within 24 h, and by using natural delectinated interleukin 2 instead of recombinant interleukin 2 products in existence at that time. Delays of more than 8 h in the addition of phytohemagglutinin-stimulated donor cells to freshly separated patient PBMCs reduced recovery. Phytohemagglutinin in cocultures and the addition of Polybrene and anti-human alpha interferon to media were not important in HIV isolation. The introduction of a consensus protocol based on this information brought most laboratories quickly into compliance. In addition, monthly monitoring has successfully maintained proficiency among the laboratories, a process that is critical for the scientific integrity of collaborative multicenter trials. Problems which might not be appreciated for months are now being resolved early, before data can be compromised unknowingly. This consensus protocol is recommended for any laboratory attempting to isolate HIV for the purpose of standardizing recovery and for accessing virologic endpoints in clinical trials. PMID- 1629337 TI - Polymerase chain reaction for diagnosis of enterohemorrhagic Escherichia coli infection and hemolytic-uremic syndrome. AB - Two pairs of oligonucleotide primers were designed to amplify fragments of the genes for Shiga-like toxin I (SLT-I) and SLT-II in a single reaction. A 370-bp segment and a 283-bp segment were amplified for SLT-I and SLT-II, respectively. The specificities of the polymerase chain reaction (PCR) amplification products were confirmed by using radioactively labeled oligonucleotide probes. SLT sequences were amplified from DNA isolated from 13 previously characterized enterohemorrhagic Escherichia coli (EHEC) strains. No amplification product was produced by using DNA from 20 non-EHEC strains. As little as one bacterial genome was detectable. PCR was then applied to DNA isolated directly from stool samples. We had to remove inhibitors of PCR that were present in lysates prepared from stool samples before amplification was achieved. First, we evaluated the sensitivity of PCR for the detection of known numbers of EHEC added to normal stools. Second, three children with SLT in their stools were shown to have SLT sequences in their stools by PCR. Two of these children had hemolytic-uremic syndrome, and a third child was asymptomatic. Stool specimens collected from another 26 asymptomatic children were negative by PCR for SLT sequences. PCR can be used to diagnose EHEC infections without prior culture of stool specimens. PMID- 1629338 TI - Molecular detection of sorbitol-fermenting Escherichia coli O157 in patients with hemolytic-uremic syndrome. AB - Shiga-like toxin-producing Escherichia coli strains of serogroup O157 were identified in 26 of 104 patients with hemolytic-uremic syndrome and in 18 of 668 patients with diarrhea. All strains were identified by colony hybridization with DNA probes complementary to Shiga-like toxin I and Shiga-like toxin II gene sequences and characterized by biochemical tests and serotyping. Seventeen of these 44 patients had E. coli O157 strains which were unusual because they fermented sorbitol within 24 h of incubation and were positive for beta glucuronidase activity. Culture filtrates of these sorbitol-fermenting strains were highly toxic to Vero cells in culture. Serological tests and DNA analysis performed by restriction endonuclease digestion of B-subunit toxin genes revealed that all 17 isolates produced Shiga-like toxin II. Although by using molecular probes we established a high frequency of sorbitol-fermenting E. coli O157 strains in the patients we examined, further studies on the prevalence of such isolates in other areas of endemic disease are clearly warranted. PMID- 1629339 TI - rRNA-based method for sensitive detection of Babesia bigemina in bovine blood. AB - Three synthetic oligonucleotide probes complementary to unique regions of Babesia bigemina small-subunit rRNA were developed for detecting the parasite in bovine blood. These probes specifically detected a parasitemia of 2 x 10(-5)% by autoradiography in less than 24 h by using a 200-microliters sample of bovine blood. These probes did not bind to total RNA or genomic DNA isolated from another closely related species, Babesia bovis, or to bovine leukocyte RNA. This method detected B. bigemina infections in calves inoculated with as few as 1,000 infected erythrocytes from the second day onward for 16 days. PMID- 1629340 TI - Use of nonradioactive DNA hybridization for identification of enterotoxigenic Escherichia coli harboring genes for colonization factor antigen I, coli surface antigen 4, or putative colonization factor O166. AB - We developed an accurate nonradioactive colony hybridization assay (NCHA) using a digoxigenin-labeled polynucleotide probe and an antidigoxigenin alkaline phosphatase conjugate for the identification of enterotoxigenic Escherichia coli (ETEC) harboring genes for colonization factor antigen I (CFA/I), coli surface antigen 4 (CS4), or putative colonization factor O166 (PCFO166). In this 2-day assay, visual registration of color intensity could be used to distinguish between CFA/I-positive strains and strains with the genetic potential to express CS4 or PCFO166. A rapid NCHA was developed by which the results could be read visually 7 h and 45 min after inoculation of the bacteria. In the rapid NCHA, densitometry verified the visual discrimination between four groups of E. coli; ETEC with the CFA/I gene, ETEC with the CS4 gene, ETEC with the PCFO166 gene, and E. coli strains that lack such genes. As a confirmatory test, plasmids from ETEC with the CFA/I, CS4, or PCFO166 gene were differentiated by their characteristic restriction fragment patterns in nonradioactive Southern blot hybridization. PMID- 1629341 TI - Comparison of the VIDAS Clostridium difficile toxin A immunoassay with C. difficile culture and cytotoxin and latex tests. AB - The VIDAS Clostridium difficile toxin A immunoassay (CDA) is a new, automated, enzyme-linked fluorescent-antibody assay for detection of C. difficile toxin A antigen in stool specimens. Simultaneous, parallel testing was performed by using the VIDAS CDA, the Culturette brand CDT latex test for C. difficile antigens, and conventional laboratory cell culture tests for C. difficile, cytotoxicity and C. difficile culture. One hundred ninety-four consecutive fresh soft or liquid stool samples submitted for C. difficile testing between July and September 1990 were evaluated. Of the 194 samples tested, 19 (10%) were from 16 patients who met our case definition for C. difficile-associated disease. The in vitro tests were evaluated in relation to two forms of a clinical case definition. In one form, a positive culture for toxin-producing C. difficile or a positive cytotoxin result obtained directly from the stool specimen was required as laboratory evidence of C. difficile. In the other, a positive result of any of the four laboratory tests was accepted for the laboratory portion of the case definition. No significant difference between the sensitivity of the VIDAS CDA and that of the Culturette brand CDT latex test was found (48 to 58% sensitivity for the CDT latex test and 52 to 63% sensitivity for the VIDAS CDA compared with 93 to 100% sensitivity for culture and 70 to 100% sensitivity for cytotoxin testing). The performance of the VIDAS CDA, however, was hampered by a high percentage of tests (19%) which gave an uninterpretable result. PMID- 1629342 TI - Characterization of rubella virus-specific antibody responses by using a new synthetic peptide-based enzyme-linked immunosorbent assay. AB - Rubella virus (RV)-specific immunoglobulin G antibodies were studied by enzyme linked immunosorbent assay (ELISA) techniques in sera from RV (RA 27/3) vaccinated individuals, patients experiencing natural RV infection, congenital rubella syndrome patients, and individuals failing to respond to repeated RV immunization. Results obtained by using whole-RV ELISAs (detergent-solubilized M33 strain or intact Gilchrist strain) and hemagglutination inhibition (HAI) and neutralization (NT) assays were compared with results obtained with the same sera by using ELISAs employing a synthetic peptide, BCH-178, representing a putative neutralization domain on the RV E1 protein. Murine RV E1-specific monoclonal antibodies with HAI and NT activities exhibited strong reactivity in ELISAs with BCH-178 peptide. In sera from RA 27/3-vaccinated individuals collected at 0 (prevaccine), 1, 2, 3, 4, 5, 6, 12, and 24 to 52 weeks postvaccine, the development of E1-peptide-reactive antibodies closely paralleled increases in RV specific antibodies measured by whole-RV ELISAs and HAI and NT assays. Similarly, sequential serum samples obtained from patients during acute and convalescent phases of natural RV infection showed a coordinate increase in RV-specific antibodies as measured by whole-RV and peptide ELISAs. Conversely, congenital rubella syndrome patient sera, although exhibiting high levels of antibody in whole-RV ELISAs, had little or no antibody directed to the neutralization domain peptide. Sera from patients failing to respond to repeated RV immunization contained very low levels of RV-specific antibody in all ELISAs. Our results that the sequence represented by BCH-178 peptide may be a previously unidentified neutralization epitope for human antibodies on the RV E1 protein and may prove useful in determining effective RV immunity. PMID- 1629343 TI - Isotype antibody response in cows to Streptococcus agalactiae group B polysaccharide-ovalbumin conjugate. AB - Adult dairy cows were immunized with group B antigen (GBA) of Streptococcus agalactiae or GBA coupled to ovalbumin, both emulsified in incomplete Freund adjuvant, and their sera were examined by an enzyme-linked immunosorbent assay measuring bovine immunoglobulin isotypes (immunoglobulin G1 [IgG1], IgG2, and IgM) specific for GBA. All of the cows possessed naturally acquired antibodies against GBA, which implied that primary antibody responses could not be studied. At the highest dose tested (200 micrograms), free GBA elicited a slight increase in antibody titers only in the IgM isotype, to which most of the naturally acquired antibodies to GBA belonged. A second administration of antigen was not more effective. The conjugate was able to induce a strong humoral response against GBA, particularly in the IgG1 and IgG2 subisotypes, and a second injection of the conjugate induced a doubling of the peak antibody titers. Therefore, conjugation of GBA to a protein carrier markedly improved the antibody response, which showed the main characteristics of T-cell dependency. The opsonic activity of serum against an unencapsulated strain of S. agalactiae was reinforced by the immunization with the conjugate. PMID- 1629344 TI - Circumsporozoite genotyping of global isolates of Plasmodium vivax from dried blood specimens. AB - The prevalence and global distribution of two circumsporozoite (CS) genotypes of Plasmodium vivax (VK210 and VK247) were determined by genetic analysis of isolates from 234 malaria-infected patients. Whole blood specimens were collected on filter paper from patients infected with malaria in Thailand, Mexico, Papua New Guinea, Peru, Afghanistan (Pakistan), India, and western Africa and from 50 asymptomatic smear-negative controls. Following extraction of DNA from the filter paper samples, the CS gene was amplified by the polymerase chain reaction and genotyped by using oligoprobes specific for the VK210 and VK247 repeat epitopes. The sensitivity of genotyping from a single blood dot was 95.2%. The VK247 CS genotype was identified in the blood of patients from all seven study areas and was the predominant form present in samples from Thailand (83%) and Papua New Guinea (90%). In contrast, VK247 DNA was present in only 9% of isolates from Mexico. Individuals infected with both genotypes simultaneously were identified in all study areas except Mexico and were particularly common in Thailand (58%) and Papua New Guinea (60%). These findings indicate that the VK247 genotype of P. vivax is widely distributed but that its prevalence varies geographically. In addition, we conclude that use of samples of whole blood on filter paper is a practical and sensitive method for determining the genotypes of large numbers of malaria isolates collected in field settings. PMID- 1629345 TI - Comparison of a chemiluminometric immunoassay with culture for diagnosis of chlamydial infections in infants. AB - The performance of Magic Lite (CIBA-Corning), a chemiluminescent immunoassay (CIA), was compared with that of culture for the diagnosis of neonatal chlamydial conjunctivitis and respiratory infection. We performed a retrospective evaluation of 51 ocular and 96 nasopharyngeal specimens previously collected for culture testing with the CIA. The sensitivities for the ocular and the nasopharyngeal specimens were 91 and 91.7%, respectively. The specificities for both sites were 100%. A subsequent prospective study evaluating 71 ocular and 38 nasopharyngeal specimens revealed sensitivities of 83.3 and 20%, respectively. The specificities for both sites were 100%. The CIA performed favorably, compared with culture, for the diagnosis of chlamydial conjunctivitis; however, the CIA appeared less sensitive for the diagnosis of respiratory infection, including pneumonia. PMID- 1629346 TI - Distribution of heartwater in the Caribbean determined on the basis of detection of antibodies to the conserved 32-kilodalton protein of Cowdria ruminantium. AB - A competitive enzyme-linked immunosorbent assay (cELISA) was developed to detect immunoglobulin G antibodies to the major 32-kDa protein of Cowdria ruminantium. A total of 1,804 serum samples collected from cattle on 19 islands in the eastern Caribbean Basin were tested by this cELISA. A total of 133 serum samples from 10 islands (Antigua, Dominica, Grenada, Guadeloupe, Martinique, Montserrat, St. Kitts, St. Lucia, St. Martin, and St. Vincent) were found to be positive. The presence of antibodies to C. ruminantium in cattle on these islands was confirmed by immunofluorescence and Western blotting (immunoblotting). In earlier studies, C. ruminantium has been demonstrated only on Guadeloupe, Antigua, and Marie Galante. This study shows that the causative agent of heartwater is now firmly established in the Caribbean. PMID- 1629347 TI - Outer membrane protein subtypes of Haemophilus influenzae type b isolates causing invasive disease in Victoria, Australia, from 1988 to 1990. AB - Outer membrane protein subtyping of 187 isolates of Haemophilus influenzae type b (Hib), isolated from children with invasive Hib disease in Victoria, Australia, showed that a single outer membrane protein subtype (1VA) was responsible for 83% of the infections. It was identical to that responsible for the majority of cases of invasive Hib disease in Europe. PMID- 1629348 TI - Bilophila wadsworthia isolates from clinical specimens. AB - Bilophila wadsworthia is an anaerobic, gram-negative, asaccharolytic, bile resistant, catalase-positive bacillus that is usually urease positive and was originally recognized in specimens of peritoneal fluid and tissue from patients with appendicitis. Additional isolations from clinical specimens, including a scrotal abscess, mandibular osteomyelitis, axillary hidradenitis suppurativa, pleural fluid, joint fluid, and blood, are described here. PMID- 1629350 TI - Selective buffered charcoal-yeast extract medium for isolation of nocardiae from mixed cultures. AB - The recovery of Nocardia species from mixed cultures is facilitated by use of a selective medium. We show that buffered charcoal-yeast extract medium with polymyxin, anisomycin, and vancomycin can be used for the selective isolation of nocardiae from contaminated specimens. PMID- 1629349 TI - Evaluation of feline immunodeficiency virus and feline leukemia virus transmembrane peptides for serological diagnosis. AB - The general model for retrovirus transmembrane (TM) proteins proposed by Gallaher et al. (W. R. Gallaher, J. M. Ball, R. F. Garry, M. C. Griffin, and R. C. Montelaro, AIDS Res. Hum. Retroviruses 5:431-440, 1989) suggests that all retrovirus TM proteins may contain an immunodominant domain (Imd-TM peptide) located at the apex of the TM polypeptide. Although this Imd-TM peptide has been shown to be immunodominant in a variety of lentivirus infections, there has not been a detailed serological analysis of an oncovirus Imd-TM peptide as a diagnostic agent. We describe here an analysis of the antigenic properties and diagnostic potentials of the predicted Imd-TM peptides of feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) in serological assays of sera from infected cats. The results of these studies demonstrate that antibodies specific to the FIV Imd-TM peptide are detected within 2 weeks postinfection, are maintained at high levels for extended periods, and are not detectable in uninfected or FeLV-infected cats. In marked contrast, the FeLV Imd-TM peptide displayed only negligible levels of serological reactivity in FeLV-infected cats. These studies indicate that the peptide is a useful reagent for the detection of antibodies to FIV. PMID- 1629351 TI - Molecular epidemiology unravels the complexity of neonatal Escherichia coli acquisition in twins. AB - Combined analysis of restriction fragment length polymorphism of regions of genes coding for rRNA (ribotyping) and esterase electrophoretic typing was used to document neonatal acquisition of Escherichia coli in twins. Our study shows vertical mother-to-infant transmission of one strain of E. coli to one twin and the development of neonatal septicemia with a distinct nonvirulent carboxylesterase type B1 E. coli strain for the other twin. PMID- 1629352 TI - Detection of rubella virus-specific polymeric immunoglobulin A by enzyme-linked immunosorbent assay in combination with streptococcal pretreatment of serum. AB - An enzyme-linked immunosorbent assay combined with streptococcal treatment of serum was assessed for its ability to detect serum polymeric immunoglobulin A. This technique detects rubella virus-specific polymeric immunoglobulin A antibody, which appears for only a short time after infection, and it is useful for serodiagnosis of recent rubella virus infection. PMID- 1629353 TI - Cross-infection risks associated with high-speed dental drills. PMID- 1629354 TI - Cross-infection risks associated with high-speed dental drills. PMID- 1629355 TI - What is APHA's future in public health? PMID- 1629356 TI - AIDS: the world situation. PMID- 1629357 TI - Budget cutting and privatization: the threat to health. AB - The worldwide drive for budget cutting and privatization, led by the WorldBank and the International Monetary Fund, has led to serious deterioration of health services as well as education, housing, nutrition and other social services in many countries. The model for this policy is the United States, which represents the pinnacle of private enterprise in the health field. The U.S. experience with this model--its effects on preventive and treatment services and health status- is reviewed. The example of the current drive toward privatization in Spain is discussed, and alternative recommendations are made to protect and improve the health of the Spanish public. PMID- 1629359 TI - Quantitative risk assessment: a tool to be used responsibly. PMID- 1629358 TI - Restrictive workplace smoking policies: impact on nonsmokers' tobacco exposure. AB - The health consequences of exposure to environmental tobacco smoke (ETS) are well documented. Although nonsmokers are generally aware of the health risks of ETS exposure, the majority of nonsmokers are regularly exposed. The most common source of exposure is the workplace. Restrictive workplace smoking policies are being used as a primary means of reducing ETS exposure. However, few studies have focused on the relation between workplace policy and ETS exposure. We performed two studies which examined the relationship between smoking policy, self-reported ETS exposure, and salivary cotinine concentrations. Study I, a pilot study, focused on a workplace-based sample of 106 volunteers; Study 2 examined exposure among 881 nonsmokers in workplace settings. In both studies, more restrictive workplace smoking policies were associated with a lower proportion of nonsmoking volunteers with detectable salivary cotinine. In Study 2, the larger study, the only other variable found to be significantly related to cotinine detection was the presence of smokers in the home. These results suggest that restrictive workplace smoking policies may reduce employees' overall ETS exposure. PMID- 1629360 TI - The Breast Cancer Screening Program in Rhode Island. AB - The Rhode Island Department of Health has undertaken a Breast Cancer Screening Program which incorporates assessment, policy development, and assurance functions, following the model proposed in the Institute of Medicine (IOM) report, The Future of Public Health. With the community's help, projects have been implemented to increase screening capacity with dedicated, state-of-the-art equipment, to increase screening accessibility, to publicize the need for mammography, and to minimize false test results. In the program's first 15 months, the proportion of women ages 40 and over who were screened with mammography according to current guidelines increased from 35 to 46 percent (from 38 to 49 percent among women ages 40-49; from 31 to 43 percent among women ages 50 and over), including 15 percent who received their first screening mammogram. Providers' recommendations and knowledge of screening guidelines were important in explaining first-time use. The Department plans to apply the IOM model in other program areas. Its adoption by others is urged. PMID- 1629361 TI - The merging of alcohol and drug treatment: a policy review. AB - Alcohol and drug treatment have separate histories in the United States. The large public treatment systems were established as separate institutions in the early 1970s and have developed separate research traditions and treatment programs. However, as a response to current treatment financing policy and epidemiologic descriptions of combined alcohol and other drug use in the population, the two treatment systems are merging at the state and local levels. This large structural change is taking place without the development and evaluation of treatment methods for combined problems and without discussion of overall health service or policy implications. This paper describes the changes occurring, examines the literature for its contributions in providing direction, and presents treatment method and policy issues which need to be part of the overall discourse. PMID- 1629362 TI - Washington State's Basic Health Plan: choices and challenges. AB - The current turbulence characterizing the health sector has engendered a limited number of state-level experiments to provide health services for the nation's 37 million uninsured. The issues and challenges generated by each program's design and implementation vary. By examining the experience of one such state program, the Washington Basic Health Plan, in some detail, this paper contributes to the policy debate regarding the possible range of solutions available to address the issue of "the uninsured." By analyzing the array of design choices available at the time the program was enacted, and why certain options were chosen rather than others, this paper points to the complex interaction of political dynamics, public policy development, and program implementation. PMID- 1629363 TI - Australia's health in the 1990s. PMID- 1629364 TI - Some epidemiological data on oral clefts in the northern Netherlands, 1981-1988. AB - Cleft lip with or without cleft palate [CL(P)] has a high prevalence [corrected] in the northern Netherlands. Several epidemiological parameters for oral clefts, including both CL(P) and cleft palate (CP), were analysed and compared with the literature. Except for the high prevalence at birth of isolated CL(P) no major differences in the pattern of occurrence described elsewhere were found. So far, descriptive epidemiological studies have not given any insight into the aetiology of this high CL(P) prevalence [corrected] in the Northern Netherlands. Therefore, case control studies on possible risk factors have been initiated. PMID- 1629365 TI - A new osteotomy for the correction of mandibular prognathism: techniques and rationale of the intraoral vertico-sagittal ramus osteotomy. AB - The sagittal split ramus osteotomy (SSRO) and the intraoral vertical ramus osteotomy (IVRO) are long established methods for correcting mandibular prognathism, each having its own advantages. However, both procedures have the same disadvantage: the potential for postoperative condylar displacement. The displacement of the condyle is mainly due to the fact that the osteotomy plane is not parallel to the original sagittal plane in which the mandible is repositioned. The author has developed a new ramus osteotomy since 1985 in which the osteotomy plane is theoretically parallel to the original sagittal plane and thereby attempting to decrease the incidence of condylar displacement. This osteotomy was designed additionally to decrease neurosensory disturbances and has the advantages of both methods, and therefore has been named 'intraoral vertico sagittal ramus osteotomy (IVSRO)'. Initial experience with the 24 prognathic patients operated on by means of the IVSRO indicated excellent clinical results. It has been noted clinically that the IVSRO is very effective in reducing postoperative iatrogenic TMJ symptoms and in treating preoperative TMJ symptoms. It has the additional effect of reducing neurosensory disturbances. This osteotomy seems to be more applicable in mandibular prognathism with excessive flaring of the ramus, particularly that associated with TMJ dysfunction, because the IVSRO has a 'condylotomy effect' and its splitting plane diverges less from the original sagittal plane than that of the SSRO and the IVRO. PMID- 1629366 TI - Mandibular autorotation in orthognathic surgery: a new method of locating the centre of mandibular rotation and determining its consequence in orthognathic surgery. AB - Rotation of the mandible is simulated through the centre of the condyle in planning orthognathic surgery. Previous studies have suggested that the initial mandibular movement is better characterized as multiple parts of the segments of a circle with the average centre located below and behind the centre of the condyle. This paper describes a method of locating the centre of mandibular rotation by computer-analysis of two lateral cephalograms with different degrees of opening. The method was used on 10 normal individuals showing an average centre of mandibular rotation 14.9 mm below and 5.0 mm behind the superior midsurface of the condyle for movements from occlusion to an opening of 10 mm. The implications of the located centre of rotation on orthognathic surgery was determined by simulating a closure of a 9.5 mm open bite. An error of up to 9.3 mm in the horizontal position of the maxilla would occur if the centre of the condyle was used. A retrospective study on 10 patients with increased anterior facial height was undertaken and a mean centre of rotation 8.4 mm behind and 25.1 mm below the centre of the condyle was found. Simulating the rotation of the mandible through the centre of the condyle would have resulted in a difference between the predicted and actual horizontal position of the maxilla ranging from 0.4-10.4 mm. It was concluded that using the centre of the condyle as the centre of mandibular rotation in the planning of superior maxillary movement with a Le Fort I osteotomy may cause considerable error in the horizontal position of the maxilla in most cases. PMID- 1629367 TI - Long-term results after horseshoe sandwich osteotomy of the edentulous maxilla as a preprosthetic procedure. AB - The long-term results in 30 patients with maxillary atrophy who have been operated on using a horseshoe sandwich osteotomy and interpositional bone grafting are reported. The postoperative period ranges from 1-4 years. Lateral cephalometric X-rays, models and clinical investigations served to determine the resorption rate and the postoperative results. It could be shown that the vertical resorption rate amounts to 1.8 mm (20%) after 3 years. The sagittal resorption rate was about 1 mm with a wide individual range. Clinical investigation revealed satisfactory results in 28 patients. PMID- 1629368 TI - Lacrimal drainage system obstruction: management and results obtained in 70 patients. AB - Causes and types of acquired obstruction of the lacrimal drainage system are discussed in 70 patients, as well as the results of their surgical treatment. Obstruction of the lacrimal drainage pathway, according to frequency, was due to: trauma (mainly naso-orbital and LeFort II fractures), post-inflammatory stenosis of the nasolacrimal duct, tumours and latrogenic injuries of the naso-lacrimal drainage system often following Caldwell-Luc operations of the maxillary sinus. The ages of patients ranged from 3-70 years. Canalicular obstruction was diagnosed in 9 (12.9%), obstruction of the lacrimal sac in 2 (2.8%), while obstruction of the naso-lacrimal duct in 50 (71.4%) patients, including 3 bilaterally. And in 9 (12.9%) patients, injury to the lacrimal system following excision of tumours of the eyelids and the medial canthal region occurred. In patients with canalicular obstruction intubation of the canaliculi was carried out and both ends of the drain were inserted into the nasal cavity for 6 months via a dacryocystorhinostomy. Total recovery was obtained in 44.5%. In lacrimal sac and nasolacrimal duct obstruction Dupuy-Dutemp's dacryocystorhinostomy was performed and 90.4% of the patients recovered. When fibrosis or extensive damage of the lacrimal sac had occurred, wide anastomosis with the nasal duct was indicated. After tumour excision, the lacrimal pathways were reconstructed by conjunctivo-rhinostomy, conjunctivo-sinusostomy or conjunctivo dacryocystorhinostomy. In 40% of the patients who underwent conjunctivo dacryocystorhinostomy a successful outcome ensued. PMID- 1629369 TI - The radial forearm free flap: our experience in solving donor site problems. AB - Special attention is paid to the problems of the donor site (the forearm) in a series of 75 patients who underwent orofacial malignancy excision. An island skin flap from the ulnar aspect of the forearm, used in 15 patients, is reported to be an improvement of the surgical technique. No healing complications were observed, and the aesthetic and functional results were very good. PMID- 1629370 TI - Neuro-ophthalmic findings in progressive supranuclear palsy. AB - We studied 104 patients with progressive supranuclear palsy (PSP), 38 of whom were examined by both a neurologist and a neuro-ophthalmologist. Neuro-ophthalmic findings that may help differentiate PSP from Parkinson's disease include vertical supranuclear ophthalmoparesis and fixation instability. Eyelid abnormalities, particularly lid retraction, blepharospasm, and "apraxia" of eyelid opening and closure, were important distinguishing signs. Although downgaze palsy is felt to be the clinical hallmark of PSP, upgaze and downgaze were equally affected at the time of diagnosis in our patients. PMID- 1629371 TI - Horner's syndrome caused by intra-oral trauma. AB - A 7-year-old boy developed a Horner's syndrome after falling on a stick that penetrated his peritonsillar soft palate. He did not suffer from any major vascular injury, and pharmacologic testing indicated a preganglionic lesion. We review previously reported cases of oculosympathetic paresis caused by surgical and nonsurgical intra-oral trauma. Because of the proximity between sympathetic and vascular structures in the lateral and parapharyngeal space, Horner's syndrome in the setting of intra-oral trauma should prompt evaluation of the internal carotid artery. Magnetic resonance imaging may be a reasonable noninvasive method for this investigation. PMID- 1629372 TI - Bilateral internuclear ophthalmoplegia in a patient with Wernicke's encephalopathy. AB - The most common cause of bilateral internuclear ophthalmoplegia is multiple sclerosis. Wernicke's encephalopathy has been reported as a cause of unilateral internuclear ophthalmoplegia but not of bilateral internuclear ophthalmoplegia. In this report, we present the case of a patient with a history of alcohol abuse and acute onset of bilateral internuclear ophthalmoplegia whose clinical course and diagnostic studies are most consistent with a diagnosis of Wernicke's encephalopathy. PMID- 1629373 TI - Simplification of the method used for biopsy of the superficial temporal artery. PMID- 1629374 TI - Craniopharyngioma: pitfalls in diagnosis. AB - A 28-year old man presented with decreased vision and a bitemporal hemianopia. Magnetic resonance (MR) imaging demonstrated what appeared to be an enlarged optic chiasm and, on T2-weighted images, hypersignal extending along the optic tracts. This was felt to represent an intrinsic chiasmal mass, most likely a chiasmal glioma. Biopsy specimens from the first craniotomy were nondiagnostic. With continued visual failure, the patient underwent a second operation, and the correct diagnosis of craniopharyngioma was established. This article emphasizes the difficulties encountered with neuroradiologic evaluation and histopathologic study of craniopharyngioma. PMID- 1629375 TI - Combined third and sixth nerve paresis following optic nerve sheath fenestration. AB - The authors report a case of transient third and sixth nerve paresis as a complication of optic nerve sheath fenestration in a patient with pseudotumor cerebri. The motility and pupillary abnormalities that are commonly associated with this procedure are reviewed briefly. PMID- 1629376 TI - Distended optic nerve sheaths in Leber's hereditary optic neuropathy. AB - Distension of the optic nerve sheaths is a feature of Leber's hereditary optic neuropathy (LHON) that has attracted attention only recently. We followed a patient with LHON for 23 years and obtained his eyes for pathological examination after death. We report the first histologic description of distension of the optic nerve sheaths, together with typical histopathological findings of LHON. Distension of the optic nerve sheaths could not be accounted for by any etiology other than LHON, although the precise pathogenic mechanisms remain enigmatic. PMID- 1629377 TI - Thyroid ophthalmopathy presenting as superior oblique paresis. AB - Six patients with thyroid ophthalmopathy presented with what appeared to be a unilateral superior oblique paresis by the three-step test, which was eventually followed by more typical findings of thyroid disease. This early motility defect in thyroid ophthalmopathy may be caused by a restrictive process due to involvement of the inferior rectus muscle. Clues to the proper diagnosis included an increase in vertical deviation in upgaze, elevation of intraocular tension in upgaze, and the lack of excyclodeviation. These features should be assessed in patients with isolated superior oblique paresis. PMID- 1629378 TI - Color vision in dominant optic atrophy. AB - The color vision of seven patients with dominant optic atrophy in four different families was studied with the following color vision tests: the Standard Pseudoisochromatic Plates part 2, the Lanthony Tritan Album, the Velhagen Pflugertrident plates, and Farnsworth Panel D 15, the Farnsworth-Munsell 100 hue test, the Nagel anomaloscope, and the Besancon anomalometer. In the first family, the mother, one of the sons, and one of the grandsons were affected. The mother had a deutantritan defect; the son and the grandson both had an undefined red green and a tritan defect. In the third family, the mother and the son were affected. Only the color vision of the son could be examined. He had a tritan defect. In the fourth family, the mother and the daughter were affected. Both had a deutan defect. In the diagnosis of dominant optic atrophy, it must be remembered that not only blue color vision defects occur, but that other kinds of defects are also possible. PMID- 1629379 TI - A possible new approach to the treatment of neuroleptic malignant syndrome. PMID- 1629380 TI - A double-blind, placebo controlled study of trazodone in patients with obsessive compulsive disorder. AB - Patients with obsessive-compulsive disorder (OCD) have been shown to be preferentially responsive to serotonin (5-HT) uptake-inhibiting antidepressants including clomipramine, fluoxetine, fluvoxamine, and sertraline. The nontricyclic antidepressant, trazodone, also possesses serotonin reuptake inhibiting properties and has been reported to be efficacious in OCD in several case reports and open trials. In order to investigate trazodone's potential antiobsessive efficacy in a controlled fashion, 21 patients with OCD were entered into a double blind, parallel design comparison of trazodone and placebo. There were no significant differences in baseline rating scores of OCD or depressive symptoms between those who entered the trazodone phase (N = 13) versus those who entered the placebo phase (N = 8). As measured by standardized OCD and depression rating scales, there was no significant difference in OCD or depressive symptoms in the 17 patients who completed 10 weeks of trazodone (N = 11, mean daily dose, 235 +/- 10 mg) versus 10 weeks of placebo (N = 6) administration. In comparison to clomipramine and fluoxetine treatment which we have found to be associated with greater than 95% reduction in platelet 5-HT concentration, there was only a 26% mean reduction in platelet 5-HT concentration after 10 weeks of trazodone administration. These results indicate that trazodone lacks substantial antiobsessive effects and is associated with only modest reductions in platelet 5 HT concentrations. PMID- 1629381 TI - Increased pulse and blood pressure associated with desipramine treatment of bulimia nervosa. AB - The cardiovascular effects of desipramine were assessed in 74 young women with bulimia nervosa participating in a 6-week double-blind, placebo-controlled study. Desipramine treatment was associated with significant increases in pulse, reclining systolic and diastolic blood pressures, and orthostatic hypotension. These effects were clearly evident in the first week of treatment and remained relatively unchanged during the subsequent 5 weeks. The mean increases in reclining systolic and diastolic pressures were approximately 10 mm Hg. Data from 16 patients treated for an additional 2 months indicated that most of the effects of desipramine on blood pressure diminished over time, whereas the effects on pulse persisted. These results differ from the commonly expected cardiovascular effects of tricyclic anti-depressants in adults. Evidence from the current study and from other reports suggests that the cardiovascular effects of tricyclic antidepressants are age-dependent. PMID- 1629382 TI - Haloperidol metabolism in psychiatric patients: importance of glucuronidation and carbonyl reduction. AB - In 39 patients who received haloperidol regularly we measured plasma concentrations of haloperidol glucuronide (HAL-GL), reduced haloperidol glucuronide (RHAL-GL), haloperidol (HAL), reduced haloperidol (RHAL), and HAL reductase activity in red blood cells. Plasma HAL-GL concentrations were significantly higher than HAL, RHAL, or RHAL-GL concentrations. Concentration ratios of total glucuronide to nonglucuronide and RHAL/HAL ratios were calculated as indices of glucuronidation and reduction capacity in each patient. The plasma glucuronidation ratios showed a significant negative correlation (r = -0.63, p less than 0.001) with the dose, while the reduction ratios showed a positive correlation (r = 0.75, p less than 0.001). No correlations were found between the HAL reductase activity in red blood cells and either the dose or RHAL/HAL. Based on these findings we suggest that glucuronidation of HAL is the major metabolic pathway of HAL in humans and its activity is important in determining steady state plasma HAL concentrations. Glucuronidation may also be a major contributing factor in the interindividual variability of HAL metabolism. PMID- 1629383 TI - A double-blind clinical trial of alprazolam, imipramine, or placebo in the depressed elderly. AB - The efficacy and safety of alprazolam as compared to imipramine or a placebo added to weekly interpersonal psychotherapy was compared in a 6-week double-blind randomized clinical trial of 35 ambulatory elderly patients with major depression. The average maximum dosage of alprazolam was 2.2 mg and the average maximum dosage of imipramine was 97.5 mg. The findings showed a rapid onset of action of alprazolam within 1 week on symptoms of depression and anxiety. The effects for imipramine were seen later in the study. There were no serious side effects that interfered with treatment. The anticholinergic effects of imipramine were the ones that most commonly interfered with treatment. Alprazolam produced the greatest number of symptoms with discontinuation, most of which were alleviated within a week. We conclude that alprazolam may be useful as an antidepressant for the elderly. More clinical trials are needed to test its efficacy in the depressed elderly with concomitant medical problems, using plasma levels. A double-blind discontinuation study of alprazolam is needed to determine the degree of symptom return. PMID- 1629384 TI - Nitrazepam clearance unimpaired in patients with renal insufficiency. AB - Eight patients with mild to moderate renal insufficiency (mean serum creatinine: 2.4 mg/100 ml) and 9 matched control subjects with normal renal function received a single 5-mg oral dose of nitrazepam, cleared mainly by hepatic nitroreduction. Serum nitrazepam levels were determined by gas chromatography during the 72 hours after dosage. Renal patients and controls were well-matched for age (74 vs. 63 years), height (165 vs. 164 cm), and weight (68 vs. 64 kg). Patients and control subjects did not differ significantly in nitrazepam elimination half-life (32 vs. 24 hour) or volume of distribution (4.2 vs. 3.6 liters/kg). Clearance was higher in patients than in controls (4.2 vs. 1.7 ml/min/kg), but the difference was not significant. Nitrazepam free fraction in serum was increased in renal patients (16.8 vs. 15.0% unbound, p = 0.08). After correction for individual values of free fraction, the two groups still did not differ in kinetic variables for nitrazepam. Thus, mild to moderate renal insufficiency does not alter the kinetics of nitrazepam. PMID- 1629385 TI - Haloperidol and reduced haloperidol in saliva and blood. AB - A total of 18 outpatients (17 male, 1 female) ranging in age from 36-66 years old were on a constant dosage of haloperidol in equally divided doses at 9:00 a.m. and 9:00 p.m. for at least 1 month. DSM-III-R diagnoses included schizophrenia (N = 9), schizoaffective disorder (N = 3), bipolar disorder (N = 4), organic mental disorder (N = 1), and delusional disorder (N = 1). Blood samples for steady-state concentrations of plasma and red blood cell haloperidol (H) and reduced haloperidol (RH) were drawn at 9:00 a.m. (12 hr trough). The haloperidol dosage was held at 9:00 a.m. until samples of whole saliva and parotid saliva could be collected for flow rates and concentrations of H and RH. Haloperidol dosages ranged from 1 mg/day to 60 mg/day (mean 11 +/- 15). Correlation coefficients were calculated for saliva concentrations versus blood levels and for saliva secretion rates versus blood levels. The correlations between whole saliva measures and blood concentrations were all higher than the correlations between parotid saliva measures and blood concentrations. In one case the higher correlation reached statistical significance. There was only one case in which substitution of saliva secretion rate improved the correlation between measures with saliva concentration. Our findings suggest that saliva measures of H and RH are useful alternatives to plasma concentrations in monitoring maintenance haloperidol treatment. PMID- 1629386 TI - A longitudinal evaluation of dexamethasone pharmacokinetics in depressed patients and normal controls. AB - Ten depressed patients and eight control subjects received 1 mg of dexamethasone intravenously at two different time points. Depressed patients were studied when they were depressed and following an improvement in their depression. In control subjects the first and second studies were performed approximately 1 month apart. Dexamethasone and cortisol were determined at 0, 5, 15, and 30 minutes, then at 1, 1.2, 2, 3, 4, 5, 6, 7, 9, 12, 17, and 24 hours following dexamethasone administration. Data from each patient was fit using a computer to a two compartment pharmacokinetic model and area under the time versus plasma concentration curve, elimination half-life, and clearance were also determined. Depressed patients exhibited a slower dexamethasone clearance and a larger area under the curve than control subjects at the first time point, but not at the second time point. The groups did not differ significantly in any of the other pharmacokinetic parameters (including distribution half-life, elimination half life, or volume of distribution) at either time point. The possible causes and implications of these findings are discussed. PMID- 1629387 TI - Predictive value of symptoms of atypical depression for differential drug treatment outcome. AB - Data for 401 depressed outpatients with mood reactivity who participated in a randomized trial comparing placebo, imipramine, and phenelzine were analyzed for predictors of differential response by stepwise multiple regression techniques. Features of the Columbia criteria for atypical depression including oversleeping, overeating, severe anergy, and pathologic rejection sensitivity were each predictive of a poorer response to imipramine than to phenelzine only when compared to those patients with none of the features. These features were not additive in their contribution to differential outcome. Lack of endogenous features was not predictive of a differential drug treatment response. Compared with patients who have no symptoms of atypical depression, patients with any of the four features had an inferior imipramine response rather than a superior phenelzine response. These analyses indicate that the clear differential responsivity to medication treatment in atypical depression is not simply related to any one defining symptom and that further correlates of this apparent biological heterogeneity need to be explored. PMID- 1629388 TI - Use of drug combinations in treatment of opioid withdrawal. AB - During the last 10 years new approaches for rapid opioid detoxification have included drug combinations such as clonidine and naltrexone to speed and ease the transition from opioid agonist to antagonist maintenance. Other drug combinations include naloxone with midazolam or methohexitone for inpatients, but rapid outpatient methods are more desirable. Clonidine combined with naltrexone enables abrupt opioid withdrawal in 3-5 days in an outpatient/day setting. This approach can be further improved by transition to the partial agonist buprenorphine from either heroin or methadone followed by a 1 day detoxification using naltrexone precipitated withdrawal, ameliorated by clonidine. PMID- 1629389 TI - Investigational protocols and physician liability. PMID- 1629390 TI - A patient of mine missed a period while taking fluoxetine; it turned out that she was not pregnant. However, the question arose about the safety of fluoxetine during pregnancy. What is known? PMID- 1629391 TI - Clomipramine treatment for generalized anxiety disorder. PMID- 1629392 TI - A case of mania associated with high-dose baclofen therapy. PMID- 1629393 TI - Abnormal liver function tests associated with lithium treatment. PMID- 1629394 TI - Activation associated with fluoxetine therapy. PMID- 1629395 TI - AIDS and dentistry. PMID- 1629396 TI - Endodontic success: is quick and easy the answer? PMID- 1629397 TI - Visuotopic organization of corticocortical connections in the visual system of the cat. AB - It has recently been demonstrated that, in contrast with the retinogeniculocortical projection, the corticocortical connections in the cat present a high degree of convergence and divergence. This suggests that some corticocortical connections link nonvisuotopically corresponding regions. Using fine-grain electrophysiological mapping and anatomical tracing, we have set out to test this possibility by placing a small injection of retrograde tracer in area 17 and by comparing the extent of visual field encoded in the region of area 18 containing labeled cells and that represented in the uptake zone. The results demonstrate that the size of the labeled region on the surface of area 18 is independent of eccentricity and that, despite its anisotrophy, this region of labeling encodes a broadly circular region of visual field that is larger than that encoded in the uptake zone of the tracer in area 17. For example, in the representation of lower visual field, a virtual point in area 17 that encodes a visual field region 4 degrees in diameter receives afferents from a region of area 18 encoding a region 11 degrees wide. Examination of the density of labeled cells in the labeled zone in area 18 reveals that the highest density is observed in a region in visuotopic correspondence with the injection site. However, high labeling density is also occasionally found in patches that do not represent the same visual field region as the injection site. Many receptive fields of neurons recorded in the labeled zone in area 18 only partially overlap or fail to overlap the visual field region encoded by the injection site. The results also demonstrate that the extent of visual field encoded in the labeled zone in area 18 is the same as that represented in the region of intrinsic labeling in area 17. It is suggested that cortical afferents coming from several cortical areas and converging on a column of cells in area 17 cover the same extent of visual field and that this cortical network constitutes the structural basis for the modulatory regions of the receptive field as well as the synchronization of neurons in different cortical areas. PMID- 1629398 TI - The selective innervation by serotoninergic axons of calbindin-containing interneurons in the neocortex and hippocampus of the marmoset. AB - The serotoninergic input to the mammalian cerebral cortex originates in the median and the dorsal raphe nuclei. Median raphe neurons have been previously shown to give rise to beaded varicose axons which form dense pericellular arrays (baskets) surrounding the soma and the proximal dendrites of certain cortical neurons. In the present study, we have searched for specific markers characterizing the neurons of the marmoset neocortex and hippocampus surrounded by these thick varicose serotonin-containing fibers. The non-pyramidal nature of these neurons, suggested by their dendritic arborization, was correlated, in immunocytochemical experiments with double-labelling to demonstrate their surrounding serotonin-containing basket and their content of glutamic acid decarboxylase (GAD) or of the calcium-binding protein calbindin. Another calcium binding protein common in numerous non-pyramidal cortical neurons, parvalbumin, was never found in neurons surrounded by serotonin-containing baskets. This organization was found in all areas of the neocortex and of the hippocampus where serotonin-containing baskets were present. One of the serotoninergic cortical inputs which originates from the brainstem tegmentum, traditionally described as "diffuse," proves to be highly selective in that a subset of its axons terminates preferentially on a subpopulation of inhibitory interneurons of the cerebral cortex. It may be emphasized that this subset of cortical interneurons has now been shown to be characterized not only by its axonal and dendritic arborization and its neurotransmitter, but also by a specific type of input which can modulate cortical function in a unique manner. PMID- 1629399 TI - Topographic organization of the cochlear spiral ganglion demonstrated by restricted lesions of the anteroventral cochlear nucleus. AB - The morphological organization of the central projections of the cat cochlear spiral ganglion into the cochlear nucleus has been investigated by creating restricted lesions in the anteroventral cochlear nucleus (AVCN) in order to ablate selectively either the lateral or the medial aspect of isofrequency projection laminae. Such lesions induced highly selective retrograde degeneration of spiral ganglion cells. Ablation of the lateral part of the AVCN resulted in degeneration of cells within the scala tympani portion of the ganglion, whereas medial lesions within the AVCN induced degeneration of the scala vestibuli portion of the ganglion. Since most, if not all, of the primary afferent axons of the cochlear nerve bifurcate into ascending and descending branches as they enter the brainstem, it is noteworthy that selective damage to the ascending branch in the AVCN was sufficient to induce retrograde degeneration of the spiral ganglion cell somata. The peripheral and central axons also degenerated, and the losses of both the radial nerve fibers in the osseous spiral lamina and the central axons passing into the modiolus displayed selective topographies that paralleled the cell loss within the spiral ganglion. The results of this study support our previous hypothesis, based upon earlier horseradish peroxidase labeling experiments, that there is a topographic organization to the projection of the spiral ganglion within the isofrequency laminae that is orthogonal to the frequency representation within the ventral cochlear nuclei (VCN). That is, in addition to the spiral frequency organization of the ganglion, represented by the dorsal-to-ventral frequency map in the VCN, there is also an orderly and sequential distribution of inputs from the vertical (scala tympani-to-scala vestibuli) dimension of the spiral ganglion across the lateral-to-medial axis of the VCN. The interaction of these two topographic representations, distributed across the three dimensions of the VCN, must partly define the selective and/or integrative neuronal response properties at this first level of central nervous system processing of auditory signals within the cochlear nuclei. PMID- 1629400 TI - Rapid changes in protein synthesis and cell size in the cochlear nucleus following eighth nerve activity blockade or cochlea ablation. AB - Destruction of the cochlea causes secondary changes in the central auditory pathway through transynaptic regulation. These changes appear to be mediated by an activity-dependent process and can be detected in the avian auditory system as early as 30 minutes after deafferentation. We compared the early changes in cochlear nucleus neurons following deafferentation by cochlea ablation with those seen following activity deprivation by perilymphatic tetrodotoxin (TTX) exposure. Protein synthesis and size of large spherical cells in the anteroventral cochlear nucleus (AVCN) of 14-day-old gerbils were measured during the first 48 hours after the manipulations. Both cochlea ablation and TTX produced a reliable decrease in protein synthesis by AVCN neurons (30-40%) by 1 hour. The magnitude of change in tritiated leucine incorporation was similar at all survival times, in both experimental groups. In contrast to the rapid changes in protein synthesis, the decrease in cell size was first evident 18 hours after TTX exposure and 48 hours after cochlea ablation. There was no significant change in protein synthesis or cell size in control groups at any of the survival times. These findings are consistent with changes in the avian auditory system in response to deafferentation and TTX exposure. Cochlea ablation and TTX exposure induced similar transneuronal changes, supporting the hypotheses that activity of auditory afferents in young mammals plays a regulatory role in the metabolism and morphology of their target neurons in the central auditory pathway, and that early changes following destruction of the peripheral receptor are due to reduction of activity-dependent interactions of presynaptic and postsynaptic cells. PMID- 1629402 TI - Light-dependent plasticity of the synaptic terminals of Mb bipolar cells in goldfish retina. AB - We recently described spine-like protrusions (spinules) from the synaptic terminals of mixed rod-cone (Mb) bipolar cells of goldfish retina that invaginated about 5% of the presynaptic amacrine cell processes (Yazulla and Studholme, J Comp Neurol 310:11, 1991). In view of reports of a light/dark dependent-plasticity on the formation of dendritic spinules on goldfish horizontal cells (Raynauld et al., Science 204:1436, 1979; Wagner, J Neurocytol 9:573, 1980), we investigated the possibility that Mb terminal spinules also might show light/dark-dependent plasticity. Retinas were obtained at noon time from light-adapted and 3-hour dark-adapted goldfish and processed for electron microscopy using conventional histological procedures and by preembedding immunocytochemistry to detect protein kinase C immunoreactivity. Two effects of light adaptation on Mb terminal morphology were observed. First, the surface of Mb terminals was significantly more irregular after dark adaptation than light adaptation. With dark adaptation, Mb terminals appeared "amoeboid," with numerous cytoplasmic extensions between the presynaptic processes. Second, spinules were sevenfold more frequent after dark adaptation than light adaptation (8% vs. 1.2% of the presynaptic processes were invaginated by spinules). We suggest that the increased frequency of spinules during dark adaptation is related to an enhancement of synaptic transmission from a minor amacrine cell input when the major input from GABAergic amacrine cells is reduced. Also, the irregular surface of dark-adapted Mb terminals may be related to the reduction of synaptic input during dark adaptation. PMID- 1629401 TI - Ascending general visceral pathways within the brainstems of two teleost fishes: Ictalurus punctatus and Carassius auratus. AB - The primary general visceral nucleus in goldfish (Carassius auratus) and catfish (Ictalurus punctatus) is located at the ventroposterior boundary of the vagal gustatory lobe and receives coelomic visceral, but not gustatory inputs. The neuronal tracer horseradish peroxidase (HRP) was employed to visualize sources of input to and ascending projections from the primary general visceral nucleus in these species. In addition, immunocytochemical techniques were utilized to define the cytological divisions within the pontine gustatory-visceral complex. The pontine secondary visceral nuclei in both catfish and goldfish contains numerous somata and fibers immunoreactive for calcitonin gene-related peptide (CGRP). In contrast, the secondary gustatory nuclei are devoid of fibers and cells immunoreactive for CGRP. In both the goldfish and the channel catfish, the primary general visceral nucleus receives input from the vagal gustatory lobe, as well as the medullary reticular formation. In the channel catfish, the primary general visceral nucleus projects bilaterally to the secondary visceral nucleus, which lies rostrolateral to the secondary gustatory nucleus in the dorsal pons. Fibers cross the midline via the rostral part of the isthmic commissure. Injection of HRP into the primary general visceral nucleus of a goldfish labels ascending fibers that project to a secondary visceral nucleus situated ventral, lateral, and rostral to the secondary gustatory complex. In general, the results indicate that general visceral systems ascend in parallel to gustatory systems within the brainstem, and that general visceral but not gustatory nuclei are immunoreactive for the peptide CGRP. PMID- 1629403 TI - Calcitonin gene-related peptide in nucleus ambiguus motoneurons in rat: viscerotopic organization. AB - Calcitonin gene-related peptide has been reported in the rat nucleus ambiguus. This nucleus comprises a dorsal division that is the source of special visceral efferents innervating the striated muscle of the upper alimentary tract and a ventral division supplying general visceral efferents primarily to the heart. The distribution of calcitonin gene-related peptide immunoreactive neurons in the two divisions was determined by using a combination of immunocytochemical techniques and fluorescent retrograde tracing. In 22 rats, injections of Fluoro-Gold were made into either the supranodosal vagus nerve, palatopharynx, larynx, esophagus, or heart. Following colchicine injection, medullary sections were processed immunocytochemically for calcitonin gene-related peptide. Injection of Fluoro Gold into the supranodosal vagus resulted in prominent labeling of neurons in the dorsal and ventral divisions of the nucleus ambiguus. The majority of fluorescent labeled neurons in the dorsal division were found to be immunoreactive for calcitonin gene-related peptide, while those labeled neurons in the ventral division were unreactive for the peptide. With esophageal, and palatopharyngeal and cricothyroid injections, many fluorescent labeled neurons that were immunoreactive for calcitonin gene-related peptide were found respectively in the compact and semicompact formations of the dorsal division. In contrast, injections of the heart resulted in fluorescent labeled neurons, which were unreactive for calcitonin gene-related peptide, localized to the external formation. The results demonstrate that calcitonin gene-related peptide immunoreactive neurons are localized entirely to the dorsal division of the nucleus ambiguus and that all striated muscular areas of the alimentary tract are innervated by calcitonin gene-related peptide containing motoneurons. The localization of calcitonin gene-related peptide to vagal motoneurons also known to contain acetylcholine and the increase in acetylcholine receptor synthesis caused by this peptide suggest that calcitonin gene-related peptide acts as a cotransmitter with acetylcholine in special visceral efferent vagal motoneurons. PMID- 1629404 TI - MRI of intracranial neurovascular compression. AB - Twelve patients with clinical indications of intracranial neurovascular compression (6, hemifacial spasm; 4, trigeminal neuralgia; 2, vertigo and tinnitus) were studied by MRI. Axial 1 mm thick slices were obtained in a 1.5 T unit using a three-dimensional (3D) fast low angle shot data set of 32 contiguous slices. The data were post-processed with multiplanar reconstruction algorithms to obtain oblique sagittal (along the long axis of a nerve) images or coronal images with a slice thickness of 0.8 mm. The MR angiographic images were also obtained from the same 3D data set with maximum intensity projection algorithms. The MR studies showed that 9 of 12 patients had neurovascular compression caused by one or two arteries. These findings were verified at surgery. In two of the remaining three patients, MRI failed to delineate the affected nerves compressed by a vein in one, and a previously applied prosthesis in the other. In the last patient no neurovascular compression was found by MRI or at surgery. PMID- 1629405 TI - High signal regions in normal white matter shown by heavily T2-weighted CSF nulled IR sequences. AB - Inversion recovery (IR) sequences with an inversion time (TI) designed to markedly reduce or null the signal from CSF (TI of approximately 2,100 ms at 1.0 T) and a very long echo time (TE) of 240 ms were used to image the brain of two normal adult volunteers, one 34-year-old man with an intrinsic tumor, and one 3 month-old infant with an infarct. Using these very heavily T2-weighted pulse sequences, adult gray and white matter showed similar signal intensity in many areas of the brain, but normal white matter in regions of the centrum semiovale, posterior internal capsule, parietopontile tract, occipitothalamic radiation, and brain stem showed a much higher signal intensity than surrounding gray or white matter. The infant displayed a low signal intensity in myelinated regions in the internal capsule and occipitothalamic radiation and a high signal in unmyelinated white matter. In many of the images there were strong similarities to the distribution of high signal within white matter seen with pulsed gradient spin echo sequences (TE 130 ms) designed to demonstrate effects due to anisotropic diffusion. Arguments are advanced to support the view that the high signal intensity in white matter tracts is due to one or more long T2 components that may be associated with unmyelinated or sparsely myelinated fibres within white matter. The resemblance to diffusion weighted images may reflect the fact that both employ long TEs and both produce a low signal from CSF. If myelin possessed a different susceptibility from axoplasm so that magnetic field gradients were generated around nerve fibres when their orientation was not parallel to B0, diffusion of water might then produce the observed dependence on fibre direction. The high signal regions in white matter are a potential source of confusion in image interpretation, and measurements of T2 in white matter need to be made with these regional variations in mind. The concept of normal appearing white matter also needs to be applied with a knowledge of these differences. The IR sequences used in this study provide a very high T2 dependence with a low signal from CSF and may be useful for detecting disease in the CNS of adults and children. PMID- 1629406 TI - Intravoxel incoherent motion (IVIM) MRI in intracranial, extraaxial tumors and cysts. AB - Intravoxel incoherent motion MRI was used to assess six intracranial, extraaxial cysts and tumors including two epidermoids, two cystic acoustic schwannomas, and two arachnoid cysts. A maximum gradient strength of 0.7 g/cm was used simultaneously along all axes (maximum gradient beta value: 445 s/mm2) and comparisons were made with an external water phantom. In epidermoid tumors the apparent diffusion coefficient (ADC) was similar to that of normal brain, thus indicating their solid nature. In acoustic schwannomas an ADC similar to the external water phantom indicated cystic components, whereas an ADC similar to brain was found in the solid portions of the tumor. The ADC of arachnoid cysts was similar to that of the water phantom, indicating their fluid nature. Due to macroscopic CSF flow, cisternal CSF showed high ADC, which enabled epidermoid tumors to be highlighted. PMID- 1629407 TI - Volume of pituitary macroadenomas: assessment by MRI. AB - A phantom study was performed to assess the accuracy of MRI in volume determination of pituitary macroadenomas, using the summation of areas technique. Five phantoms, 3-4 cm in diameter, simulating pituitary macroadenomas of various shapes, were evaluated. The volume could adequately and reproducibly be determined, regardless of minor rotational variations of the phantom position. Using a three-dimensional SE sequence with 2.5 mm slices, the error was independent of the shape of the phantom and did not differ significantly from zero (less than 5%); this sequence was found to be the best of those tested. The coefficient of variation between examinations with different tilts was 2%. In a clinical part, the volume of pituitary macroadenomas was determined with the same technique on coronal two-dimensional 5 mm images and was used as a "gold standard" to which the largest transverse, sagittal, vertical, and oblique diameters, a central tumor area, and the product of the three orthogonal diameters were correlated. In interpatient comparisons the largest diameter was found to be useful, but only as a rough measure of the tumor size. The formula 0.5 x width x length x height provided a fairly adequate estimation of the tumor volume, except in the largest tumors. In intrapatient comparisons during bromocriptine treatment, the height was found to be the best of the diameters, but the central tumor area or the product of the orthogonal diameters was preferable. PMID- 1629408 TI - CNS mycosis fungoides: CT and MR findings. AB - Mycosis fungoides (MF) is a malignant T-cell lymphoma that primarily involves the skin, but may, in its advanced stages, metastasize to internal organs. From autopsy series, CNS involvement of MF can be seen in 14% of patients. We describe the CT and MR findings in three patients with CNS metastases. The images showed various manifestations of CNS MF, including parenchymal homogeneously intensely enhancing masses and ependymal enhancement. The CSF and biopsy results were eventually diagnostic in all three cases. One patient was treated prior to pathologic diagnosis, the other two were treated after diagnosis. The tumor improved following treatment in two patients. Although the imaging findings of CNS MF are nonspecific, they can be the first evidence of the disease. PMID- 1629409 TI - Spontaneous subarachnoid hemorrhage with negative angiography: CT findings. AB - Computed tomography of 31 patients with spontaneous subarachnoid hemorrhage (SAH) but negative angiography was evaluated to find out whether the pattern of SAH as seen in CT offers indications for a possible reexamination with angiography. Based on the distribution and the amount of SAH, classification into three groups was possible: (a) 18 cases, normal CT (but blood in the CSF, gained by lumbar puncture) or SAH in the basal cisterns only; repeat angiography was negative in all these cases; (b) nine cases, SAH in the basal cisterns as well as in one or both Sylvian fissures; in addition, small amounts of blood in the interhemispheric fissure and/or in the sulci; repeat angiography revealed an aneurysm in one of these cases; (c) four cases, large quantities of blood in all subarachnoid spaces; in all but one of these cases a vascular lesion was visualized with repeat angiography or verified at autopsy. In conclusion, repeat angiography is mandatory in cases with SAH patterns that can be classified into group b or c, whereas it can be omitted in patients with small amounts of blood confined to the basal cisterns. PMID- 1629410 TI - Proton MR spectroscopy of the brain in AIDS dementia complex. AB - Proton MR spectroscopy of the brain has been undertaken in 8 healthy volunteers and in 11 patients with human immunodeficiency virus infection and varying stages of AIDS dementia complex (ADC). Spectral appearances in patients with no ADC or early ADC were not significantly different from normal volunteers. Spectra from patients with moderate to severe ADC exhibited significant reductions in levels of N-acetyl aspartate (NAA) relative to creatine (Cr) and also showed elevations in choline containing compounds (relative to Cr). Because NAA is though to be a metabolic marker for normally functioning neurons, these findings suggest the presence of neuronal injury or loss in moderate to severe ADC. The significance of these findings is discussed. PMID- 1629411 TI - Proton MR spectroscopy of experimental radiation-induced white matter injury. AB - We studied the spectroscopic appearance of radiation-induced myelinolysis in cats to understand the characteristics of proton MR spectroscopy of demyelinating disorders. Eight cats received 5,000 rads to a 1.5 x 1.5 cm area of the right cerebral hemisphere. Eight to 9 months after irradiation, a gross area of abnormal postcontrast enhancement and/or high MR signal intensity was detected in the irradiated hemisphere of six of the eight cats. Proton spectra of a 1.0 cm3 voxel in the affected region demonstrated depressed N-acetyl aspartate/creatine phosphocreatine and N-acetyl aspartate/choline-containing compound peak ratios compared with the contralateral non-irradiated brain in all cats. Elevated amino acid resonances in the 2.0-2.5 ppm range were not consistently seen in irradiated zones of the brain with pathologic findings of demyelination. In vivo proton MR spectroscopy may show differences between irradiated brain and nonirradiated brain even when histopathologic lesions are not apparent yet. PMID- 1629412 TI - MRI of the gastroepiploic artery used as a bypass graft. AB - The right gastroepiploic artery (RGEA) is recognized for its long-term patency as a coronary artery bypass graft, a property shared with the internal thoracic artery. The usefulness of MRI for noninvasive visualization and evaluation of the RGEA graft was assessed using a spine coil as the surface coil in 14 patients with graft patency verified by postoperative angiography. The graft was visualized by spin-echo imaging as a signal-void surrounded by lipomatous tissue with high-signal intensity in all 14 cases. Cine MRI was also performed in 13 of the 14 patients; in each case the graft was confirmed to contain blood flow of high-signal intensity. PMID- 1629413 TI - Evaluation of the pulmonary artery by cine MRI. AB - Twenty-four patients whose mediastinal (12 patients) and lung (12 patients) neoplasms were eventually verified were evaluated with cine MRI in addition to conventional methods (plain radiography, CT, MRI, and endoscopy). Using a 1.0 T system and gradient echo (FLASH repetition time 250-350 ms, echo time 12, flip angle 25-60 degrees) multislice pulse sequence, cine MRI was performed combined with cardiac gating. At the level of the pulmonary artery, the CT, spin echo (SE) MRI, and cine MRI findings were evaluated blindly by three groups of radiologists to determine whether the pulmonary artery was infiltrated or dynamically stenotic. Cine MRI allowed an overall diagnostic accuracy of 100% in comparison with SE MRI (91.6%) and CT (91.6%). PMID- 1629414 TI - CT of crack cocaine ingestion. AB - The imaging findings of a crack cocaine "body stuffer" are presented along with findings from in vitro experimentation with crack cocaine. It has been shown previously that contrast enhanced radiographic examinations can often outline the vessel in which ingested cocaine is contained; our work demonstrates that the crack cocaine itself may be visualized with CT performed without intravenous or oral contrast material. Due to the cost of CT, however, it is indicated only when clinically warranted to guide treatment. Positive identification of ingested crack cocaine by CT might prove helpful for both medical and legal indications. PMID- 1629415 TI - Periportal high intensity on T2-weighted MR images in acute viral hepatitis. AB - The frequency and degree of periportal high intensity (PHI) on T2-weighted images in 28 patients (32 MR studies) with acute viral hepatitis were analyzed with regard to the various levels of serum glutamic-oxaloacetic transaminase (SGOT) and clinical phases. Periportal high intensity was found in 16 of 32 MR studies (50%) and no definite PHI was found in 7 studies (22%). Periportal high intensity appeared when the SGOT level was greater than 500 IU or when the phase of the disease was early. Follow-up studies revealed that PHI decreased during clinical recovery. We conclude that the degree of PHI on T2-weighted images reflects the severity of the disease in acute viral hepatitis. PMID- 1629416 TI - CT of melanoma liver metastases: is the examination without contrast media superfluous? AB - The current method of evaluating hypervascular liver metastases with CT includes both contrast enhanced and unenhanced studies. The necessity of performing both examinations for the detection of liver metastases in the workup of malignant melanoma has not been specifically addressed. This study evaluates potential additional information derived from an unenhanced examination of the liver. We studied 55 patients with malignant melanoma who had both contrast enhanced and unenhanced CT examinations performed during the workup and staging of their disease. Sixteen patients had 89 measurable liver lesions seen on enhanced CT. Three patients had liver lesions that were too numerous to accurately measure. Unenhanced CT demonstrated only 62% of the measurable lesions. All liver lesions seen on the unenhanced images were identified on the enhanced studies. Only one metastasis was found to be comparatively smaller on the enhanced examinations. The unenhanced examinations detected no additional lesions. It is reasonable to perform only an enhanced examination during the workup and staging of malignant melanoma liver metastases. PMID- 1629417 TI - CT and MRI of siderotic regenerating nodules in hepatic cirrhosis. AB - The demonstration by CT of siderotic regenerating liver nodules in cirrhosis was evaluated and compared with that of MR imaging retrospectively in 27 patients with histologically diagnosed hepatic cirrhosis. Only in one of the two patients with marked iron deposits in regenerating nodules did CT demonstrate multiple high density nodules. In the other patient with marked iron deposits and in seven of the nine patients with moderate iron deposits, the liver parenchyma on CT was demonstrated as heterogeneous and of slightly high density without focal nodules. In 8 patients with mild to moderate iron deposits and in the 10 with no iron deposits, the liver parenchyma was homogeneous on CT. Multiple low intensity nodules in the liver were seen on fast low-angle shot (FLASH) MR images in all 17 patients with iron deposits in regenerating nodules. No low intensity nodules were seen on FLASH MR images in the 10 patients with no iron deposits. If there are iron deposits above a certain level, siderotic regenerating nodules may appear as nodules of high density on CT or as heterogeneous regions of high density liver parenchyma. Magnetic resonance is more sensitive than CT in demonstrating siderotic regenerating nodules. PMID- 1629418 TI - CT of parapelvic cystic renal cell carcinoma. AB - Parapelvic renal cysts are benign ubiquitous lesions of the renal sinus frequently demonstrated on CT and ultrasonography. Occasionally a renal parenchymal mass will grow so that its epicenter is within the renal sinus. We report two cases of surgically proven cystic renal cell carcinoma centered in the renal sinus with no apparent connection to the renal parenchyma. Cystic renal cell carcinoma must be excluded whenever a parapelvic cyst with atypical features is encountered on cross-sectional imaging studies. PMID- 1629419 TI - The reliability of radiologists' quality assessment of MR pelvic scans. AB - The purpose of this study was to test the reliability of radiologists' subjective assessment of the quality of MR scans of the pelvis. A four-grade ordinal subjective scale, based on the degree of artifact and contrast between pelvic organs, was developed in a pilot study by two MR radiologists. Forty pelvic scans were graded "blindly" in random order by the same two "practiced" MR radiologists, and an objective measurement of scan artifact was obtained for each scan. Twenty-eight pelvic scans were also graded by two "unpracticed" radiologists not involved in the development of the scale. For the practiced radiologists, the interobserver percentage agreement was 80% (weighted kappa of 0.78) and the intraobserver percentage agreement was 75% (weighted kappa of 0.73). For the unpracticed radiologists the percentage agreement was 61% and the weighted kappa was 0.55. The correlation between the subjective and objective measurement was only 0.27. In conclusion, the objective measurement of scan artifact showed poor correlation with the radiologists' subjective assessment of scan quality. The subjective assessment demonstrated satisfactory reliability and, therefore, could be considered as an additional outcome measurement for scan quality in clinical trials or as a relevant measure of quality assurance. PMID- 1629420 TI - Knee joint hyaline cartilage defects: a comparative study of MR and anatomic sections. AB - The value of routinely used MR sequences in the detection of focal changes of femorotibial articular cartilage was studied. T1-weighted, proton density, and T2 weighted SE as well as gradient echo images were acquired in 20 cadaveric knees (56-88 years old, mean 73.8 years). Three hundred five coronal and sagittal (3 mm) anatomic sections were prepared, and 82 areas of cartilage defects were identified. Initially, in an unblinded fashion, correlation of MR scans and anatomic sections was performed. Fifty-nine lesions (72.0%) were detectable on T1 weighted images, 57 (70.0%) with meniscal windowing, 49 (60.0%) on proton density images, 56 (68.3%) on T2-weighted images, and 54 (65.9%) on gradient echo images. Sixty-eight (83.0%) were visible on at least one type of imaging sequence. Most defects presented as a focus of abnormal signal. Subsequently, images of a subset of 35 pathologic and 35 normal cartilage surfaces were blindly evaluated by two osteoradiology fellows. Sensitivity was 71.4% for the detection of focal cartilage changes, specificity was 68.6%, and accuracy was 70.0%. We conclude that the value of those MR sequences that are routinely used in the analysis of internal derangements of the knee in the detection of focal defects of the hyaline cartilage is limited. PMID- 1629421 TI - MRI of patellar tendon anterior cruciate ligament autografts. AB - Twenty-one MR examinations were performed in 15 patients with clinically stable knees after arthroscopic anterior cruciate ligament (ACL) reconstruction with patellar bone-tendon-tibial bone autografts. The postoperative interval ranged from 3 months to 3 years 3 months (average 9.5 months). Proton- and T2-weighted sagittal images with axial and oblique sagittal T1-weighted images were obtained. The MR appearance of the autografts was categorized depending on distribution of dark signal band into type 1 (continuous, two patients), type 2 (proximal half, eight patients), type 3 (distal half, two patients), and type 4 (nonvisualization, three patients). There was no change in appearance of the grafts in those who had a second imaging within 1 year postoperatively. We conclude that the normal ACL autograft has a variable appearance and that criteria used in evaluating the native ligament is inadequate to assess the autografts. PMID- 1629422 TI - Bone metastases from breast cancer: value of CT bone windows. AB - A pilot study was organized to compare the utility of scintigraphy, radiographic bone surveys, and conventional CT bone windows (CTBWs) in judging therapeutic response of bone lesions in patients with metastatic breast carcinoma. Twenty-six patients with stage IV disease and documented bone metastases were evaluated over a 2 year period. Discordance in the assessment of therapeutic response was greatest (56% discordance) between bone scans (BSs) and conventional CTBWs. In 77% of the discordant observations, the assessment by conventional CTBWs agreed with the patients' clinical response to therapy. Our preliminary results suggest that posttherapy review of conventional CTBWs provides useful clinical information about therapeutic response and exceeds the contribution of BSs in this regard. PMID- 1629423 TI - MRI and ultrasound detection of asymptomatic thyroid nodules in hyperparathyroidism. AB - A retrospective MRI and ultrasound (US) study of 50 patients with hyperparathyroidism and no history of thyroid disease was done. The purpose was to compare the sensitivity of both methods in the detection of asymptomatic thyroid nodules, as well as to determine the prevalence of thyroid abnormalities in patients with hyperparathyroidism. All the patients underwent MR and 33 were also studied by high-resolution US. Magnetic resonance imaging was performed on a 1.5 T unit, using T1-(500-700/20) and T2-(2,000/20 and 70) weighted images. Axial sections (5 mm with a 1 mm interval between them) were obtained along the neck. Ultrasonography was performed using a 10 MHz linear array transducer. The prevalence of thyroid nodules was 46% in the 50 patients studied by MR imaging. In the subgroup of patients studied by both methods, US depicted nodules in 48% of patients, and MR depicted nodules in 45%. Magnetic resonance imaging and US detected a high frequency of thyroid nodules in patients with hyperparathyroidism. This high frequency makes the detection of an intrathyroidal parathyroid adenoma problematic. PMID- 1629424 TI - Rapid automated algorithm for aligning and reslicing PET images. AB - A computer algorithm for the three-dimensional (3D) alignment of PET images is described. To align two images, the algorithm calculates the ratio of one image to the other on a voxel-by-voxel basis and then iteratively moves the images relative to one another to minimize the variance of this ratio across voxels. Since the method relies on anatomic information in the images rather than on external fiducial markers, it can be applied retrospectively. Validation studies using a 3D brain phantom show that the algorithm aligns images acquired at a wide variety of positions with maximum positional errors that are usually less than the width of a voxel (1.745 mm). Simulated cortical activation sites do not interfere with alignment. Global errors in quantitation from realignment are less than 2%. Regional errors due to partial volume effects are largest when the gantry is rotated by large angles or when the bed is translated axially by one half the interplane distance. To minimize such partial volume effects, the algorithm can be used prospectively, during acquisition, to reposition the scanner gantry and bed to match an earlier study. Computation requires 3-6 min on a Sun SPARCstation 2. PMID- 1629425 TI - Simultaneous display of multiple MR parameters with "quantitative magnetic color imaging". AB - A new technique for simultaneous display of multiple MR parameters with a single color-coded image is described. The method is based on the multiparametric nature of MR signals and benefits from the physiologic ability to discriminate color levels better than gray levels. The T1 and T2 relaxation rate maps are first obtained from multi-echo SE and partial saturation sequences. Each parameter is subsequently represented with one or with a combination of two fundamental colors (red, green, blue) into a composite quantitative magnetic color image. Each mixture of chromatic components in the magnetic color image represents a unique combination of the two relaxation parameters, easily interpretable by the human eye, without loss of anatomic information. The potential advantages of the technique are discussed and some practical applications are presented. PMID- 1629426 TI - MRI of absent left pulmonary artery. AB - Unilateral absence of a pulmonary artery, more accurately referred to as unilateral proximal interruption of a pulmonary artery, is a rare congenital anomaly that may occur as an isolated lesion or in association with other congenital cardiovascular abnormalities. Diagnosis of associated lesions is imperative as early detection and intervention may significantly improve the patient's prognosis. We present the case of an adult patient who had come to our attention after suffering neurological decompression illness related to scuba diving. The patient's cardiopulmonary anatomy was evaluated using MRI gated spin echo, cine, and breath-held fast spoiled recalled echo sequences. PMID- 1629427 TI - Usefulness of multiangle MRI in aortic arch dissection. AB - A multiangle scan technique was used in combination with usual spin echo and cine MR techniques to study a patient with aortic arch dissection. The intimal flap was seen with each technique and the jet into the entry site was observed with cine MR technique. Exact short axis images of aortic arch were obtained only with multiangle scan. Retrograde dissection and involvement of left subclavian artery were detected clearly on the short axis images. PMID- 1629428 TI - High attenuation mucous plugs in allergic bronchopulmonary aspergillosis: CT appearance. AB - Allergic bronchopulmonary aspergillosis is an immunologic disease characterized by bronchiectasis and recurrent mucous plugging in asthmatics. The usual CT appearance is that of low attenuation branching structures corresponding to impacted dilated bronchi. We report a patient with allergic bronchopulmonary aspergillosis and mucous plugging manifested by high attenuation structures on CT. A follow-up examination demonstrated resolution of the mucous secretions and residual bronchiectasis. Possible etiologies for this CT appearance are discussed. PMID- 1629429 TI - CT of pseudohydronephrosis: hydroureter in a weight lifter. AB - A case of bilateral pseudohydronephrosis and hydroureter produced by markedly hypertrophied psoas muscles in a weight lifter is presented. Plain film and CT findings of the case are discussed together with the topographic anatomical explanation of the radiologic findings. PMID- 1629430 TI - Diffusely calcified renal cell carcinoma: CT features. AB - Calcifications of renal masses are common. They are usually dense, partial, small, punctate, and linear opacities. Diffuse calcification is an extremely rare feature of renal masses. Generally, calcified renal cell carcinomas are hypovascular, with calcifications in the interstitium, and they also contain fibrotic capsules, necrotic areas, or hyalinization. We recently observed a renal neoplasm with diffuse calcification on CT and intermediate vascularity on angiography, which was diagnosed histologically as renal cell carcinoma, clear cell type. Interestingly, there were numerous calcific deposits within the tumor cells. PMID- 1629431 TI - Pelvic Castleman disease: CT and MR appearance. AB - The localized form of Castleman disease is rare and of unknown origin. Pelvic location of the disease is unusual. We report the CT and MR appearance of a case of pelvic Castleman disease presenting with characteristic calcifications and hypervascularity. PMID- 1629432 TI - MRI of sarcoid spondylodiskitis. AB - We report the MR appearance of a rare case of sarcoidosis of the spine presenting as spondylodiskitis. Vertebral and disk signal changes were typical for diskitis. In the appropriate clinical setting the differential diagnosis of diskitis should include sarcoidosis. PMID- 1629433 TI - Pyogenic granuloma gravidarum of the nasal fossa: CT features. AB - We present a case of a pregnant patient with a rapidly growing mass within the nasal fossa that was imaged by CT 2 weeks postpartum. Concern for malignancy existed and biopsy was performed, revealing pyogenic granuloma gravidarum. This uncommon lesion should be considered in any gravid patient when a mass occurs within the mouth or nasal fossa. PMID- 1629434 TI - MRI of concurrent spinal meningioma, ependymoma, and syringomyelia. PMID- 1629435 TI - Absent medial segment of the left hepatic lobe: CT appearance. PMID- 1629436 TI - CT-guided suprasternal approach for mediastinal biopsy. AB - A case involving the use of the suprasternal approach for CT-guided biopsy of small retrosternal lesions is discussed, with the mention of some technical details. PMID- 1629437 TI - Health: always under attack. PMID- 1629438 TI - Measurement of preventive resin restorations using computer profilometry. AB - The amount of extracoronal material placed when a tooth is restored with a preventive resin restoration (PRR) was quantitatively measured together with the projected area of each cavity preparation. Thirty-three patients (mean age 11 yrs, 6 mos) requiring a PRR on a lower first permanent molar were selected. Impressions of the teeth were made with polyvinylsiloxane before and after cavity preparation and then restored with P-50 and Concise sealant. Following occlusal adjustment, a third impression was taken. Replicas were digitized using computer profilometry. Computer images of occlusal surfaces were superimposed using a "goodness of fit" method. The volume of extracoronal material placed on all molar teeth (n = 33) was X = 6.52 +/- 2.9 mm3. The mean depth applied was X = 222.52 +/ 83.09 mu and the mean area of material applied over the entire tooth surface was X = 27.13 +/- 5.72 mm2. The cavity preparations occupied, on average 19.02 percent of the occlusal surface. PMID- 1629439 TI - Dental erosion associated with asymptomatic gastroesophageal reflux. AB - An eight-year-old girl presented with severe erosion of the primary dentition and early erosion of the erupted permanent teeth. Although the pattern of erosion was consistent with that seen with acid erosion, the diagnosis could not be elucidated from the patient's symptoms, or medical or dental history. A 24-hour pH probe study documented severe gastroesophageal acid reflux. Oral salivary pH tested during sleep nightly for one week revealed low oral pH. Treatment with metoclopramide and ranitidine was instituted to decrease acid availability for reflux. Custom-fitted, maxillary and mandibular trays were fashioned to deliver sodium fluoride gel twice daily, and fissure sealants were placed in the hopes of retarding erosion of existing permanent teeth, as well as preventing similar erosion of erupting permanent dentition. PMID- 1629440 TI - Mesiodens in the primary dentition stage: a radiographic study. AB - Five hundred and forty-three Chinese patients in the primary dentition stage were evaluated for mesiodens with maxillary, anterior occlusal films. Compared with other studies, a higher prevalence was found, using different age-groups and diagnostic methods. The distributions of mesiodens by sex, location, and direction were also studied. Because mesiodens could interfere with normal development of the occlusion, especially in the early mixed dentition stage, early diagnosis, using appropriate radiographs during the primary dentition stage, could lead to more comprehensive treatment planning. PMID- 1629441 TI - Multispecialty team management of a case with impacted maxillary permanent canines. AB - A fifteen-year-old Chinese girl presented with unerupted maxillary permanent canines impacted against the roots of the central incisors, causing malalignment of the maxillary incisors. The canines were fully formed and their apices closed. The potential path of eruption of the canines contraindicated surgical exposure, followed by orthodontic traction. It was decided to transplant the impacted canines to their normal positions, and then align the maxillary anterior teeth, using a fixed orthodontic appliance. The transplantations and the orthodontic treatment were successful, and neither transplant showed signs of root resorption, periodontal pockets, mobility, or pain, three years after surgery. Root canal therapy was performed on the canines after transplantation, because their apices were closed. They were stained by the amalgam in the access cavities, but both responded well to nonvital bleaching using 30 percent H2O2. PMID- 1629442 TI - Midline correction by extraction of the remaining mandibular canine: myth or reality. AB - Standard of practice does not always equal standard of care. When faced with a problematic situation, the dentist will either treat from experience, or else depend on what has been suggested by others. In some cases, anecdotal information may not be applicable. Recommended clinical procedures have not always been supported by adequate research. Although midline correction has been expressed as a certainty, it does not always occur. Patience on the part of the practitioner will allow the child to be observed periodically, and at the same time allow the dentition to develop naturally. Orthodontic treatment can always be used, once the permanent canines erupt. PMID- 1629443 TI - "Rediscovering" the health status of Native Americans. AB - The demographic and health characteristics of the Native American population differ from those of the general population. A review is provided for concerned pediatric dental practitioners. PMID- 1629444 TI - Hispanic children: an increasing reality in pediatric dental practice. AB - By the end of the current decade, the 11.5 million Hispanic children (less than eighteen years of age) in the United States will represent the largest population of minority children. Almost 48 percent of all Hispanic persons living in poverty were children (1989). Data show great need for dental care among these people, with only limited access to adequate care. PMID- 1629445 TI - Root canal filling materials for primary teeth: a review of the literature. AB - In summary, there is no known ideal root canal filling material for primary teeth. The closest to the ideal appears to be a calcium hydroxide-iodoform mixture. More histopathologic studies as well as long-term clinical studies are needed on this material. PMID- 1629446 TI - Ectopic eruption of a mandibular first permanent molar: report of an unusual case. AB - A case history of an ectopically erupting mandibular left first permanent molar is described. Most notable are the unusual findings of a missing mandibular left second premolar and an epithelial cyst and a horizontally impacted mandibular left second permanent molar. A unique treatment plan called for the extraction of the mandibular second primary molar, excision of the cyst, and removal of the mandibular left second and third molars. In hindsight, other procedures might have served the patient better. PMID- 1629447 TI - Dentocraniofacial structure with complete anodontia of permanent teeth: report of case. AB - Dentocraniofacial structure with ectodermal dysplasia, showing complete anodontia of permanent teeth, was examined. Except for a slight decrease of the sweat pore count, the patient was free of signs of ectodermal dysplasia, other than odontoplasia. Furthermore, her family history had no record of hypodontia or anodontia. We attempted to clarify the role of tooth growth in the dentocraniofacial development. Cephalometric analyses revealed the extreme limitation of the maxillary and vertical growth of the lower face, and a retracted mandibular alveolus front. We concluded that the role of tooth growth was significant in the development of the maxillary and alveolar bone, but not in the development of the mandible. PMID- 1629448 TI - Primary maxillary bilateral birooted canines: report of two cases. PMID- 1629449 TI - The effect of orthodontic retention on the mechanical properties of the periodontal ligament in the rat maxillary first molar. AB - The load-deformation curves obtained by extraction of the rat maxillary first molar from its socket in the dissected jaw were analyzed so that the effect of orthodontic retention on the mechanical properties of the periodontal ligament could be examined. An elastic band was inserted between the rat maxillary first and second molars for four days, and then the interdental space was filled with resin for four or eight days. The average interdental spaces between the teeth ranged from 315 to 398 microns during the experimental period. The maximum shear load, elastic stiffness, and failure energy in shear decreased markedly following application of an orthodontic force, but they increased gradually and reached control levels on the 8th day after the retention. Maximum shear deformation at maximum load was not significantly different between the experimental and control teeth during the experimental period. It is suggested that, following orthodontic tooth movement, occlusal function was restored after a relatively short retention period, as was the impaired mechanical strength of the periodontal ligament. PMID- 1629450 TI - Site-specific expression of collagen I and XII mRNAs in the rat periodontal ligament at two developmental stages. AB - In mammals, the periodontal ligament (PDL) is a highly specialized tissue which facilitates tooth eruption and lends mechanical support to the tooth once in occlusion. The PDL extracellular matrix fibers play a major role in such functions. During its development, the spatial arrangement of the PDL extracellular matrix undergoes rapid changes. So that it could be determined whether the structural alteration in the PDL is associated with changes in the expression of collagenous proteins with different functional properties, the transcriptional patterns of collagens I and XII were examined. The maxillary dento-alveolar segments, each containing three molars, from 25-day-old and 40-day old Sprague-Dawley rats were selected as being representative of developing and matured tissues, respectively. Rat alpha 2(I) collagen cDNA and rat alpha 1(XII) collagen cDNA were used as molecular probes for identification of the corresponding mRNAs by RNA transfer blot analysis, RNase protection assay, and in situ hybridization. The results showed that alpha 2(I) collagen mRNA was expressed in both developing and matured tissues. However, the level of expression decreased with maturity. In contrast, the expression of alpha 1(XII) collagen was increased in the matured tissue as compared with the developing tissue. In situ hybridization in these tissues indicated that the expression of alpha 1(XII) collagen mRNA was limited to the mature stage of PDL development. It is suggested that collagen fibril arrangement during PDL development may be related to the expression of collagen XII. PMID- 1629451 TI - Clinical criteria for the diagnosis of salivary gland hypofunction. AB - There is considerable difficulty in the making of initial clinical decisions as to whether a given patient has salivary gland hypofunction, and hence requires additional salivary gland evaluation. This study identified a set of four clinical measures that, together, successfully predicted the presence or absence of salivary gland hypofunction. The four measures were: dryness of lips, dryness of buccal mucosa, absence of saliva produced by gland palpation, and total DMFT; they were derived from discriminant analysis of data collected from 71 individuals with normal and low salivary flow rates. These measures are proposed as criteria for clinical decision-making, as well as for classification of patients in studies of salivary gland dysfunction syndromes. This study also identified unstimulated whole salivary flow rates of 0.12-0.16 mL/min as the critical range separating individuals with salivary gland hypofunction from those with normal gland function. PMID- 1629452 TI - Progression of approximal caries in relation to iatrogenic preparation damage. AB - The aim of the present study was to evaluate the effect of iatrogenic preparation damage on the need for operative caries treatment of approximal surfaces, adjacent to Class II amalgam restorations. The material was collected by 77 dentists from the Public Dental Child Health Service in Denmark. It consisted of die-stone models of 187 first-time Class II preparations, adjacent to 190 unfilled approximal surfaces of 58 primary and 132 permanent teeth. The cavity preparations were performed in children between 4 and 17 years of age. They were all filled with amalgam. Information about operative treatment and exfoliation or extraction of the preparation teeth and the adjacent teeth during the following seven years was obtained from the patients' records. Stereomicroscopic examination of the models revealed preparation damage on 64% of the unfilled approximal surfaces in primary teeth and on 69% of the corresponding test surfaces in permanent teeth. During the observation period, operative treatment was performed on 10% of the undamaged test surfaces in primary teeth and on 35% of the damaged ones (p less than 0.05). The corresponding figures for test surfaces in permanent teeth were 6% and 15% (p less than 0.05). It is concluded that iatrogenic preparation damage is a frequent side-effect of operative intervention with approximal caries lesions, and represents a dental health problem, since the damage increases caries progression and the perceived need for restorative therapy of the adjacent teeth. PMID- 1629453 TI - The influence of denture-wearing and age on the oral microflora. AB - The effects of denture-wearing and age on the prevalence of selected bacteria of dental significance and on the carriage of opportunistic pathogens in molar plaque and whole saliva were determined in 120 healthy subjects, 41 of whom wore partial dentures. The subjects were divided into four age groups: 20-39 years (group A), 40-59 years (group B), 60-79 years (group C), and greater than or equal to 80 years (group D). The proportions, mean log10 viable counts, and isolation frequency of yeasts and lactobacilli in saliva and plaque were consistently higher in partial-denture wearers. The proportions of staphylococci and mutans streptococci were also raised in denture wearers, but these differences did not reach statistical significance. When the data were analyzed for age effects, both yeasts and lactobacilli were found to be increased in saliva with age, but statistically significant differences were generally found only between denture wearers in group D and subjects in the control group A. The isolation frequency of yeasts from plaque was also significantly higher in denture wearers of the oldest age group (D) compared with those in group A. A. viscosus predominated over A. naeslundii in the older age groups, regardless of the presence of dentures. Enterobacteria were isolated occasionally but only from the saliva of denture wearers in group D. Spirochetes and black-pigmented anaerobes were generally found in lower numbers in denture wearers. Collectively, the data show that components of the oral microflora in adults can be independently influenced by both age and the wearing of partial dentures. PMID- 1629454 TI - Fluoride intake from beverage consumption in a sample of North Carolina children. AB - Since the 1940's, the prevalence of dental fluorosis has increased in the US, concomitant with a reduction in dental decay. These changes have been attributed in part to the widespread use of systemic and topical fluorides. Various sources of increased systemic fluoride exposure have been investigated. However, little is known regarding fluoride intake from beverages in a sample of children of ages susceptible to dental fluorosis. The purpose of this study was to estimate the amount of fluoride ingested from beverages by a sample of North Carolina (NC) children of ages 2-10 years. Data on beverage consumption were collected by means of a diary format. A questionnaire was included so that demographic information and self-assessment on the accuracy of the diaries could be obtained. Beverages reported in the diaries were purchased, and their fluoride content was assayed. Daily total fluid intake ranged from 970 to 1240 mL, and daily beverage consumption ranged from 585 to 756 mL. The estimated mean daily fluoride intakes from beverages for children 2-3, 4-6, and 7-10 years of age were 0.36, 0.54, and 0.60 mg, respectively. PMID- 1629455 TI - Initial dissolution rate studies on dental enamel after CO2 laser irradiation. AB - The influence of CO2 laser irradiation on the dissolution behavior of human dental enamel has been investigated. Human enamel was irradiated by a continuous wave CO2 laser at 10.6 microns and initial dissolution rates (IDRs) were measured in 0.1 mol/L acetate buffer, pH = 4.5, both with and without calcium and/or phosphate common ion, by means of a rotating disk assembly. The effects of (1 hydroxyethylidene) bisphosphonic acid (EHDP), fluoride (F), and dodecylamine HCl (DAC) at various levels upon the IDR were also determined. All of the findings were consistent with the hypothesis that CO2 laser irradiation converts dental enamel to hydroxyapatite (HAP) possessing site #2 character (Yamamoto et al., 1986). The dissolution driving force function, KHAP = aCa10aPO4(6)aOH2, was found to have a value of 10(-129.9) after being lased, as compared with 10(-121.4) before being lased. The IDR values for EHDP (3 mmol/L) and DAC (3 mmol/L) were essentially zero as expected for site #2 HAP. For solution F, the deduced dissolution driving force function, KFAP = aCa10aPO4(6)aF2 was 10(-128.6) after being lased as compared with 10(-116.3) before being lased. These results all support the hypotheses (1) that laser irradiation may convert the surface of human dental enamel to an apatite of significantly lower effective solubility (i.e., site #2 HAP) than that of unlased enamel; and (2) that there is significant synergism between laser treatment and these chemical dissolution rate inhibitors (again consistent with site #2 HAP). Simple model calculations indicate that, in both the presence and absence of fluoride, these laser-induced changes in the driving force for dissolution should dramatically lessen the susceptibility of enamel to the types of acid challenge that might be encountered in the mouth. PMID- 1629456 TI - Synthesis and evaluation of new oxaspiro monomers for double ring-opening polymerization. AB - Polymerization with expansion in volume can be achieved with spiro orthocarbonate monomers through a double ring-opening process wherein two bonds are cleaved for each new bond formed. The resulting expansion can be applied to counter the polymerization shrinkage associated with the conventional methacrylate monomers used in dental composites and thereby provide formulations with drastically reduced degrees of shrinkage. New monomers have been prepared that exhibit enhanced reactivities and ring-opening efficiencies compared with earlier free radical-polymerizable oxaspiro compounds. In dental composite formulations, the monofunctional oxaspiro monomers provided DTS values equivalent to those of the controls under certain curing conditions; however, only modest reductions in polymerization shrinkage were observed. 2,3-Bis(methylene) spiro orthocarbonate monomers with a conjugated diene structure were also synthesized and evaluated. These novel monomers appear to offer significant potential for future development of free-radical ring-opening polymerization. While visible-light-cured formulations of the bis(methylene) compounds with methacrylate comonomers did not yield acceptable composite materials in this initial attempt, the high reactivity and the ability to form rigid, cross-linked polymers make this type of monomer worthy of continued investigation. These properties may allow the bis(methylene) oxaspiro monomers to be used alone or in concert with other ring-opening monomers for special applications. PMID- 1629457 TI - Effect of contact area size on enamel and composite wear. AB - The effect of contact area dimensions on the wear of composite specimens and their opposing enamel cusps was evaluated in vitro. Thirty-six standardized cylindrical composite specimens were placed into metal cavities (8 mm x 2 mm) and divided randomly into five groups. The composite used was a fine-particle hybrid and was stressed as follows: storage in 75% aqueous ethanol solution for 24 h, toothbrush/toothpaste-abrasion for 30 min, followed by 300 thermal cycles in water ranging from 5 degrees to 55 degrees C and simultaneous 120,000 occlusal chewing loads at a frequency of 1.7 Hz at 53 N maximum force. In group 1 (n = 12), the occlusal chewing loads were applied by palatal cusps of extracted human maxillary molars with natural morphology. In groups 2 to 5 (n = 6), the cusp tips had standardized contact area dimensions of 0.26, 0.38, 1.18, and 4.10 mm2, respectively. Wear of composite specimens and antagonistic enamel cusps (means +/ SD) was assessed in microns by means of a 3-D scanner. Additionally, the contact surfaces of the restorations and of the antagonistic enamel cusps were evaluated by SEM. Increases in enamel contact areas after being loaded were measured by means of a digitizer and expressed in percent of the initial size before stress exposure. The wear of the composite specimens varied from 69.8 +/- 19.9 to 9.5 +/ 3.6 microns, and that of antagonistic enamel cusps from 31.3 +/- 3.4 to 8.8 +/- 1.5 microns. The increase in contact area varied between 27.8 and 0.1%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629458 TI - The effects of cleaning on the kinetics of in vitro metal release from dental casting alloys. AB - The kinetics of the release of elements from six dental casting alloys into cell culture medium was assessed by means of atomic absorption spectroscopy. Alloys were evaluated in the polished and polished-cleaned conditions so that the effects of cleaning could be determined. Auger scanning microscopy was used for analysis of the surfaces of selected alloys before and after exposure to the cell culture medium. Release patterns for each element were characterized by the shape of the dissolution vs. time curve, concentration of the element at 12 h as a percentage of the 72-hour concentration, and the relative slope of the curve from 48 to 72 h. Three patterns of release were observed for elements in these alloys. Type I patterns had logarithmic shapes with relatively large 12-hour concentrations and low 48-72-hour slopes. Type II patterns had logarithmic shapes but with moderate 12-hour concentrations and 48-72-hour slopes. Type III patterns were polynomial in shape, had relatively low 12-hour concentrations, and had large 48-72-hour slopes. Cleaning did not change the pattern of release but did generally significantly decrease the quantities of elements released (p = 0.05). The type of dissolution vs. time curve appeared to be dependent upon the element and the composition of the alloy. When cleaning reduced dissolution, surface analyses showed that the cleaning process increased the abundance of elements such as Au and Pd and reduced the abundance of Ag and Cu. Elements which were released from the alloys were more abundant on the surface than in the bulk in both polished and polished-cleaned conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629459 TI - Dental plaque and calculus: risk indicators for their formation. AB - The aim of this study was to determine the levels of plaque and subgingival calculus accumulation and to evaluate their correlations with periodontal disease, as well as to evaluate the correlations with race, age, and gender in an attempt to identify risk indicators for plaque and calculus formation. A total of 508 adults 25-73 years of age was examined, and plaque assessment, gingival bleeding assessment, probing pocket depth, and attachment levels were determined. The mean percent visible plaque was 73.5% (range, 8.3-100%), mean percent of bleeding surfaces 38.5% (range, 0-100%), and the mean percent teeth with subgingival calculus 39.6% (range, 0-100%). The mean probing pocket depth in the group was 2.5 +/- 0.6 mm (SD), and mean clinical attachment loss was 2.1 +/- 1.1 mm. The majority (63%) were classified as having "Moderate" periodontal disease, 7% were "Healthy", and the remaining 30% had "Established" periodontal disease. Plaque and calculus showed statistically significant relationships to the three disease categories (p less than 0.001). Multiple step-wise regression analyses on the correlations between plaque and periodontal disease, race, age, and gender resulted in an overall correlation coefficient of r = 0.25 (p less than 0.001). Disease status ("Established") contributed most (p = 0.003), followed by race (Blacks; p = 0.015), gender (Males; p = 0.022), and age (55-73 yr; p = 0.022), to the correlation with plaque. For subgingival calculus, the overall correlation coefficient was r = 0.44 (p less than 0.001). However, only two of the variables- namely, disease status (p less than 0.001) followed by race (p = 0.017)--showed statistically significant correlations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629460 TI - Microbiological aspects of the chemical control of plaque and gingivitis. AB - Antimicrobial agents, delivered either by mouthrinse or toothpaste, can be used to maintain plaque at levels compatible with oral health by (a) reducing existing plaque, (b) preventing the formation of new plaque, (c) selectively inhibiting those particular bacteria that are associated with disease, and (d) inhibiting the expression of virulence determinants. Although many antimicrobial agents would appear to be suitable for plaque control, few have been found to possess clinical efficacy. This is because of inherent problems in the mode of action of agents in the mouth, and with difficulties with their formulation into dental products. Currently formulated antimicrobial agents include metal salts (e.g., zinc, stannous, copper), phenols (triclosan), plant extracts (sanguinarine), enzymes (e.g., glucanase, amyloglucosidase/glucose oxidase), "essential oils" (e.g., thymol, menthol), and bisbiguanides (chlorhexidine). Although many of these agents exhibit a broad spectrum of antimicrobial activity in the laboratory, they may display valuable selective properties on plaque. The effect of an agent will be concentration-dependent. Initially, the inhibitor may be briefly at levels above its MIC, but thereafter, it will be desorbed off oral surfaces and operate at sub-lethal concentrations. At these latter levels, agents can be effective by inhibiting metabolism (e.g., acid production, protease activity), and slowing bacterial growth. Agents with complementary modes of action are being combined to increase their antibacterial effectiveness. The long term use of dental products containing antimicrobial agents should not (a) disrupt the natural balance of the oral microflora, (b) lead to colonization by exogenous organisms, or (c) lead to the development of microbial resistance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629461 TI - Delivery of antiplaque agents from dentifrices, gels, and mouthwashes. AB - Antiplaque agents delivered from toothpastes, gels, or mouthrinses can augment mechanical oral hygiene procedures to control the formation of supragingival plaque and the development of early periodontal disease. Clinically effective antiplaque agents are characterized by a combination of intrinsic antibacterial activity and good oral retention properties. The overall oral retention of an antiplaque agent is determined by the strength and rate of association of the agent with its receptor sites and the accessibility of these sites. The substantivity of an antiplaque agent and its clearance from the oral cavity are determined by the rate of dissociation of the agent from the receptor sites and the salivary composition and flow rate. Positively charged and non-charged organic molecules, metal ions, enzymes, and surface-active agents have all been considered as antiplaque agents. To exert clinical antiplaque activity, an antimicrobial agent must be formulated in a chemically compatible delivery vehicle to give optimal release and uptake to the sites of action in a biologically active form during its time of application. In principle, antiplaque activity may be enhanced by combining antimicrobial agents with broadly similar, but complementary, modes of action. Alternatively, the activity of a single agent may be increased by use of a retention aid to enhance oral substantivity. Substantial evidence exists to demonstrate the validity of the first approach. However, there are few data, as yet, to support the effectiveness of the second. The oral mucosa is the bulk retention site for all clinically proven antiplaque agents. Plaque, the pellicle-coated tooth surface, and saliva are probably all sites of biological action. A detailed understanding of the interactions between agents and the various receptor sites, and of the importance of these receptor sites to biological activity, is generally lacking. PMID- 1629462 TI - Agents for the management of plaque and gingivitis. AB - Numerous chemical agents have been evaluated for the supplementation of patient dependent mechanical plaque control and thus the reduction or prevention of oral diseases. Agents discussed in this paper are those most frequently evaluated in recent studies and include chlorhexidine, essential oils, triclosan, sanguinarine, fluorides, oxygenating agents, quaternary ammonium agents, prebrushing rinses, enzymes, and antibiotics. Of the agents discussed, the greatest effect on the reduction of plaque and gingivitis can be expected from chlorhexidine, essential oils, and triclosan-containing products. These chemical agents vary in dosage form and include mouthrinses, gels, and dentifrices. Some may also be of value as irrigants. Adverse effects vary according to the chemical agent and include poor taste, burning sensation of oral tissue, staining of teeth and soft tissues, excess supragingival calculus, oral lesions in young patients, and allergic reactions. When a product is selected for a patient, consideration should be given to necessity, efficacy, adverse effects, and cost-effectiveness. PMID- 1629463 TI - New agents in the chemical control of plaque and gingivitis: reaction paper. AB - The inadequacy of traditional methods in controlling plaque and gingivitis has led to an increasing interest in the chemical approach, especially using toothpastes and mouthrinses. Various agents have been tested by a variety of experimental designs. Further work in this field should include monitoring the effect of long-term use on the oral ecology and an appraisal of the experimental designs used in longitudinal studies of antiplaque and antigingivitis agents. PMID- 1629465 TI - A case for clinical research. PMID- 1629464 TI - New agents in the chemical control of plaque and gingivitis--reaction paper. AB - The papers of Drs. Christersson, Marsh, Cummins, and Ciancio focus on the issues and problems associated with the efficacious delivery of chemical agents intended to control plaque and gingivitis. The infectious nature of periodontal disease, the importance of oral microbial ecology, the success of triclosan formulations, and the review of our current knowledge based upon clinical trials are emphasized. PMID- 1629466 TI - Consent for dental therapy in severely ill patients. AB - This article provides an overview of legal standards for informed consent, and discusses this in the context of dental care for elderly or severely ill patients. Legal analysis is made on variations in state common law and legislation, focusing on the difference between a practitioner-oriented approach versus a patient-oriented approach to informed consent. Analysis is also made regarding advance health care directives in cases of patient incapacity. The purposes of this article are to provide interested dental educators with an understanding of the important legal concepts in this area and the nuances of state law, and to discuss how these can be properly applied in facilities that treat severely ill or geriatric patients. PMID- 1629467 TI - Perceived mistreatment of graduating dental students: a retrospective study. AB - This study assessed types and sources of perceived mistreatment among graduating dental students. A total of 38 of 46 (83 percent) students anonymously completed a mistreatment questionnaire. All 38 students perceived experiencing at least one type of mistreatment from some source and reported an average of about 35 separate incidents. Psychological mistreatment was most frequent with physical mistreatment reported relatively infrequently. Classmates and clinical faculty were the most frequent sources of mistreatment. Sexual harassment was perceived by about one-third of the students. The potentially adverse effects of perceived mistreatment were discussed with a view to improving dental education through an emphasis on stress management, environmental change, and self-responsibility for health designed to enhance the personal growth of each dental student. PMID- 1629468 TI - The search for a profile of aptitudes that characterize dentists. AB - This article is a reinterpretation of an unsuccessful attempt to develop a standard battery of aptitude measures to distinguish practicing dentists. Of 22 potential predictors used by a firm specializing in aptitude testing and career counseling, the national sample of 116 dentists tested showed few differences from the norm group, and some differences were counterintuitive. For example dentists performed no better than the norm on spatial visualization and worse than the norm on several measures of language skill and on finger dexterity. Based on these findings, this paper argues that a broad conceptualization is required when attempting to characterize the aptitudes necessary to complete dental education and to maintain a dental practice. The apparent inconsistency between these findings and successful prediction of performance in laboratory courses using available admissions instruments is explained. PMID- 1629469 TI - Interrater agreement on subgingival calculus detection following scaling. AB - Accurate and reliable detection of subgingival calculus is a difficult skill which relies on subjective tactile sensations for determinations. This one year retrospective study examined the interrater agreement among a large, generalized pool of clinical examiners who scored residual subgingival calculus after student scaling. Four thousand one hundred and sixty tooth surfaces were analyzed for examiner agreement. Interrater reliability for all paired clinical ratings was low (Kappa = .33). A second, companion study evaluated accuracy and reliability using raters' assessments about the existence of simulated calculus on the root surfaces of manikin teeth. In the second study interrater reliability also was low (Kappa = .34); the true positive and true negative ratios were 49 percent and 88 percent respectively, while the false positive and false negative ratios were 12 percent and 51 percent. These data suggest that there is a need in periodontics for effective examiner calibration methodologies and objective subgingival calculus detection techniques. PMID- 1629470 TI - Broadening the scope of dental education. PMID- 1629471 TI - The Buffalo approach to changing the basic science curriculum or toiling and dreaming in the vineyards of dental education. PMID- 1629472 TI - Basic sciences instruction, the Columbia University Model. PMID- 1629473 TI - Status of practice administration curricula. PMID- 1629474 TI - Dental hygiene enrollment and institutional affiliation. PMID- 1629475 TI - Occluded-ear simulator with variable acoustic properties. AB - Ear simulators were designed to replicate acoustical characteristics of the average adult ear. Due to variability of ear-canal geometry and eardrum impedance among individuals, the possibility of any one person exhibiting such "average" characteristics--especially if that person is a child and/or has a conductive pathology--is remote. Thus, ear simulators have been of only peripheral value when prescribing a hearing aid (a high output impedance device) to fit the acoustical requirements of a particular patient. Reported herein is development of a programmable artificial ear (PAE) that can account for individual differences in ear-canal geometry and eardrum impedance. It consists of a 2.0-cc coupler, microphone, amplifier, computer, PAE code, and a computer card and/or software for digitization and Fourier transformation. Required input data includes ear-canal dimensions, eardrum impedance, and output impedance of the hearing aid being tested. Sound-pressure recordings produced in the 2.0-cc coupler by the hearing aid are adjusted by the computer to what they would have been had the recordings been made at the eardrum of a particular patient wearing the same hearing aid. Good agreement was observed between experiment and theory for one test case involving a totally occluding miniature earphone. PMID- 1629476 TI - Auditory nerve representation of a complex communication sound in background noise. AB - A population study of auditory nerve responses in the bullfrog, Rana catesbeiana, analyzed the relative contributions of spectral and temporal coding in representing a complex, species-specific communication signal at different stimulus intensities and in the presence of background noise. At stimulus levels of 70 and 80 dB SPL, levels which approximate that received during communication in the natural environment, average rate profiles plotted over fiber characteristic frequency do not reflect the detailed spectral fine structure of the synthetic call. Rate profiles do not change significantly in the presence of background noise. In ambient (no noise) and low noise conditions, both amphibian papilla and basilar papilla fibers phase lock strongly to the waveform periodicity (fundamental frequency) of the synthetic advertisement call. The higher harmonic spectral fine structure of the synthetic call is not accurately reflected in the timing of fiber firing, because firing is "captured" by the fundamental frequency. Only a small number of fibers synchronize preferentially to any harmonic in the call other than the first, and none synchronize to any higher than the third, even when fiber characteristic frequency is close to one of these higher harmonics. Background noise affects fiber temporal responses in two ways: It can reduce synchronization to the fundamental frequency, until fiber responses are masked; or it can shift synchronization from the fundamental to the second or third harmonic of the call. This second effect results in a preservation of temporal coding at high noise levels. These data suggest that bullfrog eighth nerve fibers extract the waveform periodicity of multiple harmonic stimuli primarily by a temporal code. PMID- 1629477 TI - Auditory intensity perception: successive versus simultaneous, across-channel discriminations. AB - This study measures the ability of observers to compare the intensities of two stimuli occupying different frequency regions. It includes three experiments, each experiment having two conditions. In one condition, the two stimuli to be compared were presented simultaneously within each interval; this condition has been called profile analysis. In the other condition, the two stimuli were presented successively within each interval. Because the overall level of the stimuli was randomized between intervals, the observers were encouraged to compare the intensities of the two stimuli within each observation interval rather than between intervals. The stimuli were two simple tones in experiment 1 and two tonal complexes in both experiments 2 and 3. The stimuli used in experiments 2 and 3 differed in frequency. The results show that simultaneous comparisons are superior to successive comparisons. For simple tones, the difference in threshold is about 8 dB; for complexes with 10 to 11 components, the difference in threshold is about 15 dB. These differences can be explained by assuming that internal noises in different channels were partially correlated when stimuli in those channels were presented simultaneously and were independent when the stimuli were presented successively. Cancellation of the correlated noise is therefore possible with simultaneous comparisons, making such discrimination better than that achievable with successive comparisons. PMID- 1629478 TI - A new technique for measuring spectral shape discrimination. AB - A new technique is described for studying the ability of listeners to discriminate between sounds on the basis of spectral shape, a process called "auditory profile analysis." The advantage of the technique is that it reduces the range of the random rove in level necessary to provide a specified limit on the performance which listeners could achieve by "level detection;" that is, by employing a detection strategy based solely on comparisons of stimulus level. Thresholds were measured for the just-discriminable "ripple" (a pattern of alternating intensity increments and decrements) in an equal-amplitude, multitone reference spectrum for a group of normal-hearing listeners. Broadband, high-pass and low-pass filtered conditions were tested. The results indicated that the thresholds obtained using the new technique were well below the lowest level achievable by level detection (referred to as the "level-detection limit") in all conditions using a 20-dB random within-trial rove in overall level. The lowest threshold occurred for the broadband stimulus while the highest threshold was observed for the most extreme high-pass filtered condition. The new technique appears to be well-suited for study of profile analysis in hearing-impaired listeners where stimulus bandwidth and rove range are limited. PMID- 1629479 TI - Overshoot in normal-hearing and hearing-impaired subjects. AB - Overshoot was measured in both ears of four subjects with normal hearing and in five subjects with permanent, sensorineural hearing loss (two with a unilateral loss). The masker was a 400-ms broadband noise presented at a spectrum level of 20, 30, or 40 dB SPL. The signal was a 10-ms sinusoid presented 1 or 195 ms after the onset of the masker. Signal frequency was 1.0 or 4.0 kHz, which placed the signal in a region of normal (1.0 kHz) or impaired (4.0 kHz) absolute sensitivity for the impaired ears. For the normal-hearing subjects, the effects of signal frequency and masker level were similar to those published previously. In particular, overshoot was larger at 4.0 than at 1.0 kHz, and overshoot at 4.0 kHz tended to decrease with increasing masker level. At 4.0 kHz, overshoot values were significantly larger in the normal ears: Maximum values ranged from about 7 26 dB in the normal ears, but were always less than 5 dB in the impaired ears. The smaller overshoot values resulted from the fact that thresholds in the short delay condition were considerably better in the hearing-impaired subjects than in the normal-hearing subjects. At 1.0 kHz, overshoot values for the two groups of subjects more or less overlapped. The results suggest that permanent, sensorineural hearing loss disrupts the mechanisms responsible for a large overshoot effect. PMID- 1629480 TI - Effect of spectral envelope smearing on speech reception. I. AB - The effect of reduced spectral contrast on the speech-reception threshold (SRT) for sentences in noise and on phoneme identification, was investigated with 16 normal-hearing subjects. Signal processing was performed by smoothing the envelope of the squared short-time fast Fourier transform (FFT) by convolving it with a Gaussian-shaped filter, and overlapping additions to reconstruct a continuous signal. Spectral energy in the frequency region from 100 to 8000 Hz was smeared over bandwidths of 1/8, 1/4, 1/3, 1/2, 1, 2, and 4 oct for the SRT experiment. Vowel and consonant identification was studied for smearing bandwidths of 1/8, 1/2, and 2 oct. Results showed the SRT in noise to increase as the spectral energy was smeared over bandwidths exceeding the ear's critical bandwidth. Vowel identification suffered more from this type of processing than consonant identification. Vowels were primarily confused with the back vowels /c,u/, and consonants were confused where place of articulation is concerned. PMID- 1629481 TI - Pitch discrimination and phase sensitivity in young and elderly subjects and its relationship to frequency selectivity. AB - Frequency difference limens for pure tones (DLFs) and for complex tones (DLCs) were measured for four groups of subjects: young normal hearing, young hearing impaired, elderly with near-normal hearing, and elderly hearing impaired. The auditory filters of the subjects had been measured in earlier experiments using the notched-noise method, for center frequencies (fc) of 100, 200, 400, and 800 Hz. The DLFs for both impaired groups were higher than for the young normal group at all fc's (50-4000 Hz). The DLFs at a given fc were generally only weakly correlated with the sharpness of the auditory filter at that fc, and some subjects with broad filters had near-normal DLFs at low frequencies. Some subjects in the elderly normal group had very large DLFs at low frequencies in spite of near-normal auditory filters. These results suggest a partial dissociation of frequency selectivity and frequency discrimination of pure tones. The DLCs for the two impaired groups were higher than those for the young normal group at all fundamental frequencies (fo) tested (50, 100, 200, and 400 Hz); the DLCs for the elderly normal group were intermediate. At fo = 50 Hz, DLCs for a complex tone containing only low harmonics (1-5) were markedly higher than for complex tones containing higher harmonics, for all subject groups, suggesting that pitch was conveyed largely by the higher, unresolved harmonics. For the elderly impaired group, and some subjects in the elderly normal group, DLCs were larger for a complex tone with lower harmonics (1-12) than for tones without lower harmonics (4-12 and 6-12) for fo's up to 200 Hz. Some elderly normal subjects had markedly larger-than-normal DLCs in spite of near-normal auditory filters. The DLCs tended to be larger for complexes with components added in alternating sine/cosine phase than for complexes with components added in cosine phase. Phase effects were significant for all groups, but were small for the young normal group. The results are not consistent with place-based models of the pitch perception of complex tones; rather, they suggest that pitch is at least partly determined by temporal mechanisms. PMID- 1629482 TI - Test of a model of auditory object formation using intensity and interaural time difference discrimination. AB - A model of auditory object formation and an experimental evaluation of the model are described. Specifically, predictions for intensity discrimination and interaural time difference discrimination for the central component of a three component harmonic complex are evaluated empirically. The onset time of the central, target component is varied relative to the onset times of the remaining, interferer components in order to vary the degree of fusion (versus perceptual segregation) of the target and the interferers. The model, which is based on the idea of attenuation of the components in the nonattended auditory image (in the case of segregated images), predicts lower sensitivity to information at the target component for the fused versus segregated target, and equal sensitivities for completely segregated targets and targets presented in isolation. Results are presented for four subjects with component frequencies of 400, 600, and 800 Hz and with onset time differences of 0 or 250 ms. The target duration was always 100 ms and offset times were the same for all components. The subjective results were as expected, with synchronous onsets yielding one sound object, and asynchrony of the central component yielding two sound objects. Also, the empirical results on interference in the synchronous case were in qualitative agreement with the above predictions. However, significantly more interference was found than was predicted for both synchronous and asynchronous conditions. In fact, the amount of interference found contradicts the simple attenuation model of object formation. PMID- 1629483 TI - Tongue-tip trills and vocal-tract wall compliance. AB - The effect of vocal-tract wall compliance on tongue-tip trills is to create a favorable pressure-flow relation at the tongue tip for sustained vibration. The governing equations are derived for a model based on this mechanism, and data on unvoiced trills are used to help set parameters for a numerical simulation of the model. PMID- 1629484 TI - Temporal measures of anticipatory labial coarticulation for the vowel/u/: within- and cross-subject variability. AB - The timing of upper lip protrusion movements and accompanying acoustic events was examined for multiple repetitions of word pairs such as "lee coot" and "leaked coot" by four speakers of American English. The duration of the intervocalic consonant string was manipulated by using various combinations of /s/, /t/, /k/, /h/, and /#/. Pairwise comparisons were made of consonant string duration (acoustic /i/ offset to acoustic /u/ onset) with durations of: protrusion movement beginning to acoustic /u/ onset, maximum acceleration of the movement to acoustic /u/ onset, and acoustic /u/ onset to movement end. There were some consonant-specific protrusion effects, primarily on the movement beginning event for /s/. Inferences from measures of the maximum acceleration and movement end events for the non-/s/ subset suggested the simultaneous and variable expression of three competing constraints: (1) end the protrusion movement during the voiced part of the /u/; (2) use a preferred movement duration; and (3) begin the /u/ related protrusion movement when permitted by relaxation of the perceptually motivated constraint that the preceding /i/ be unrounded. The subjects differed in the degree of expression of each constraint, but the results generally indicate that anticipatory coarticulation of lip protrusion is influenced both by acoustic-phonetic context dependencies and dynamical properties of movements. Because of the extensive variation in the data and the small number of subjects, these ideas are tentative; additional work is needed to explore them further. PMID- 1629485 TI - Phonation threshold pressure: a missing link in glottal aerodynamics. AB - Phonation threshold pressure has previously been defined as the minimum lung pressure required to initiate phonation. By modeling the dependence of this pressure on fundamental frequency, it is shown that relatively simple aerodynamic relations for time-varying flow in the glottis are obtained. Lung pressure and peak glottal flow are nearly linearly related, but not proportional. For this reason, traditional power law relations between vocal power and lung pressure may not hold. Glottal impendance for time-varying flow should be defined differentially rather than as a simple ratio between lung pressure and peak flow. It is shown that the peak flow, the peak flow derivative, the open quotient, and the speed quotient of inverse-filtered glottal flow waveforms all depend explicitly on phonation threshold pressure. Data from singers are compared with those from nonsingers. The primary difference is that singers obtain two to three times greater peak flow for a given lung pressure, suggesting that they adjust their glottal or vocal tract impedance for optimal flow transfer between the source and the resonantor. PMID- 1629486 TI - Vocal intensity in speakers and singers. AB - Vocal intensity is studied as a function of fundamental frequency and lung pressure. A combination of analytical and empirical models is used to predict sound pressure levels from glottal waveforms of five professional tenors and twenty five normal control subjects. The glottal waveforms were obtained by inverse filtering the mouth flow. Empirical models describe features of the glottal flow waveform (peak flow, peak flow derivative, open quotient, and speed quotient) in terms of lung pressure and phonation threshold pressure, a key variable that incorporates the Fo dependence of many of the features of the glottal flow. The analytical model describes the contributions to sound pressure levels SPL by the vocal tract. Results show that SPL increases with Fo at a rate of 8-9 dB/octave provided that lung pressure is raised proportional to phonation threshold pressure. The SPL also increases at a rate of 8-9 dB per doubling of excess pressure over threshold, a new quantity that assumes considerable importance in vocal intensity calculations. For the same excess pressure over threshold, the professional tenors produced 10-12 dB greater intensity than the male nonsingers, primarily because their peak airflow was much higher for the same pressure. A simple set of rules is devised for predicting SPL from source waveforms. PMID- 1629487 TI - Controlling changes in vocal tract resistance. AB - There is some evidence that speech aerodynamics follows the rules of a regulating system. The purpose of the present study was to assess how the speech system manages perturbations that produce "errors" within the system. Three experimental approaches were used to evaluate the physiological responses to an imposed change in airway resistance. The first involved subjects with varying degrees of velopharyngeal inadequacy. The second and third approaches involved noncleft subjects whose airway was perturbed by bleed valves and bite blocks during consonant productions. The pressure-flow technique was used to measure aerodynamic variables associated with the production of test consonants. The results of this study provide additional evidence that the speech system actively responds to perturbations in ways that tend to minimize a change in consonant speech pressures. The degree of success in stabilizing pressures appears to reflect the capability of the system to use whatever articulatory and respiratory responses are available. PMID- 1629488 TI - Relative timing characteristics of hearing-impaired speakers. AB - Speech duration characteristics of phrase-level utterances produced by 26 severely and profoundly hearing-impaired adults were examined acoustically using relative timing measures. The measures were then compared to the same utterances produced by 13 normal-hearing adults. Although absolute speech durations of the hearing-impaired subjects were significantly longer than their normal-hearing counterparts, relative timing did not differ between groups. Findings are discussed in relation to the biological constraint hypothesis associated with speech timing, as well as the role of auditory feedback in models of speech production. PMID- 1629489 TI - Speech of cochlear implant patients: a longitudinal study of vowel production. AB - Acoustic parameters were measured for vowels spoken in /hVd/ context by four postlingually deafened recipients of multichannel (Ineraid) cochlear implants. Three of the subjects became totally deaf in adulthood after varying periods of partial hearing loss; the fourth became totally deaf at age four. The subjects received different degrees of perceptual benefit from the prosthesis. Recordings were made before, and at intervals following speech processor activation. The measured parameters included F1, F2, F0, SPL, duration, and amplitude difference between the first two harmonic peaks in the log magnitude spectrum (H 1-H2). Numerous changes in parameter values were observed from pre- to post-implant, with differences among subjects. Many changes, but not all, were in the direction of normative data, and most changes were consistent with hypotheses about relations among the parameters. Some of the changes tended to enhance phonemic contrasts; others had the opposite effect. For three subjects, H 1-H2 changed in a direction consistent with measurements of their average air flow when reading; that relation was more complex for the fourth subject. The results are interpreted with respect to: characteristics of the individual subjects, including vowel identification scores; mechanical interactions among glottal and supraglottal articulations; and hypotheses about the role of auditory feedback in the control of speech production. Almost all the observed differences could be attributed to changes in the average settings of speaking rate, F0 and SPL, which presumably can be perceived without the need for spectral place information. Some observed F2 realignment may be attributable to the reception of spectral cues. PMID- 1629490 TI - Acoustic and perceptual characteristics of voicing in fricatives and fricative clusters. AB - Several types of measurements were made to determine the acoustic characteristics that distinguish between voiced and voiceless fricatives in various phonetic environments. The selection of measurements was based on a theoretical analysis that indicated the acoustic and aerodynamic attributes at the boundaries between fricatives and vowels. As expected, glottal vibration extended over a longer time in the obstruent interval for voiced fricatives than for voiceless fricatives, and there were more extensive transitions of the first formant adjacent to voiced fricatives than for the voiceless cognates. When two fricatives with different voicing were adjacent, there were substantial modifications of these acoustic attributes, particularly for the syllable-final fricative. In some cases, these modifications leads to complete assimilation of the voicing feature. Several perceptual studies with synthetic vowel-consonant-vowel stimuli and with edited natural stimuli examined the role of consonant duration, extent and location of glottal vibration, and extent of formant transitions on the identification of the voicing characteristics of fricatives. The perceptual results were in general consistent with the acoustic observations and with expectations based on the theoretical model. The results suggest that listeners base their voicing judgments of intervocalic fricatives on an assessment of the time interval in the fricative during which there is no glottal vibration. This time interval must exceed about 60 ms if the fricative is to be judged as voiceless, except that a small correction to this threshold is applied depending on the extent to which the first-formant transitions are truncated at the consonant boundaries. PMID- 1629491 TI - Automated detection of the tongue surface in sequences of ultrasound images. AB - An image processing system has been developed for a Macintosh II personal computer. It is designed to process sequences of sagittal tongue sections that are digitized in real time and stored in standard tagged image file format (TIFF). The successive processing steps are: (a) a low-pass filter for noise reduction, (b) a resampling of the sector of interest in polar coordinates, (c) a matched filter (vertical differentiator) for the enhancement of the tissue/air interface in the surface region of the tongue, and (d) an extraction of border points by searching for an optimal radial path along the angular dimension. This latter task is achieved by dynamic programming, which has the following advantages. First, due to the use of a global criterion to guide the detection, it is very robust. Second, as a result of certain restrictions of the allowable transitions, the extracted contours are smooth. Finally, the method permits the specification of particular predefined contour points. This system was implemented in a program that can handle image sequences in a fully automatic mode. Results obtained using ultrasound data are presented. PMID- 1629492 TI - Calculating acoustical properties of cells: influence of surface topography and liquid layer between cell and substrate. AB - In this paper, a mathematical formulation is presented to compute the V(z) of a tapering layered solid and applying this formulation to the determination of acoustic properties of biological cells and tissues. The formulation is adopted in the simplex inversion algorithm to obtain the acoustic properties of a tapering cell from its V(z) values. The influence of two parameters had been considered: The tapering angle and the presence of a thin liquid layer present between cells and the substratum to which they adhere. Up to a tapering angle less than 10 degrees, it can be safely neglected. However, if a larger angle is neglected, then the acoustic wave velocity in the cell is overestimated. Cell thickness estimation is not affected significantly when the tapering angle is ignored. The calculations of acoustic properties of cells are considerably influenced by the introduction of a thin fluid layer between the solid substratum and the overlying cell, neglecting the presence of at least a very thin layer (20 30 nm), in general, results in a considerable overestimation of sound velocity. The reliability of the data calculated from V(z) values was ascertained using an independent method to determine cell thickness by calculating it from the interference fringe pattern obtained with the reflection-interference light microscope. The shape of the glutaraldehyde-fixed cells was similar to fried eggs. The highest sound velocities were found close to the periphery of the dome shaped cell center. In the very center and over most of the area of the thin periphery, sound velocity was close to that in saline. PMID- 1629493 TI - Identification of human myocardial infarction in vitro based on the frequency dependence of ultrasonic backscatter. AB - It has been reported previously that acute and mature myocardial infarction in dogs can be differentiated in vitro and in vivo by ultrasonic tissue characterization based on measurement of the frequency dependence of ultrasonic backscatter. To characterize human infarction with an index of the frequency dependence of backscatter that could be obtained in patients, cylindrical biopsy specimens from 7 normal regions and 12 regions of infarction of 6 fixed, explanted human hearts in 2-deg steps around their entire circumference with a 5 MHz broadband transducer were insonified. One to six consecutive transmural levels were studied for each specimen. The dependence of apparent (uncompensated for attenuation or beam width) backscatter, /B(f)/2, on frequency (f) was computed from spectral analyses of radio-frequency data as /B(f)/2 = afn, where from theoretical considerations the magnitude of n decreases as scatterer size increases. Apparent integrated backscatter was computed as the average of /B(f)/2 from 3 to 7 MHz. The average value for n for normal tissue (0.9 +/- 0.1) exceeded that for tissue from regions of infarction (0.6 +/- 0.1; p less than 0.05). Infarct manifested a significant decrease of n from epicardial to endocardial levels (epi----mid----endo: 0.9----0.7----0.2; p less than 0.05) whereas normal tissue manifested similar values for n at each transmural level (0.8----1.1--- 0.9; p = NS). Average integrated backscatter across all transmural levels for infarct was significantly greater than for normal tissue (-48.3 +/- 0.5 vs -53.4 +/- 0.4 dB, infarct versus normal; p less than 0.05). The presence of fibrosis was associated with smaller values of n and greater integrated backscatter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629494 TI - Corrected values for Annex B of ISO 1999. PMID- 1629495 TI - Asthma with sulfite intolerance in children: a blocking study with cyanocobalamin. AB - Sulfites have been implicated as the cause of bronchospasm in some subjects with asthma. However, there is still no universally accepted explanation of the pathogenesis of these reactions. We have studied five children with asthma with metabisulfite intolerance confirmed by oral challenge testing. The challenge test with metabisulfite was repeated after premedication of all the patients with 1.5 mg of oral cyanocobalamin. In four of the five patients treated with cyanocobalamin, bronchospasm did not develop in the second metabisulfite challenge. The possible mechanisms are discussed. PMID- 1629496 TI - The allergens of Epicoccum nigrum Link. I. Identification of the allergens by immunoblotting. AB - Two atmospheric isolates of Epicoccum nigrum (EN) were grown under sporulation conditions. Dialyzed extracts of spores, (greater than 95% pure) and pure mycelia were used for skin testing, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunoblotting. By skin testing, 49 of the 126 atopic patients were found to be sensitive to EN in St. Louis, Mo., and Corpus Christi, Texas, combined. On immunoblotting, which was performed on 17 sera, 44 bands (12.3 to 119.0 kd) were detected; six were unique to spore, four were unique to mycelium, and 34 were common to both. No single band bound IgE from all sera. The most frequent band corresponding to 42 kd occurred in 11 sera. Five other bands were recognized by more than one half, whereas the remainder bound fewer sera. All skin test-positive patients had positive immunoblots; the number of bands recognized varied from three to 25. Spore or mycelium-specific, as well as common bands were recognized by 13 of 17 sera. Two sera recognized only spore and mycelium-specific bands. Only spore-specific bands were bound by two sera. No strain differences were detected. The binding patterns were comparable in the sera from both St. Louis, Mo., and Corpus Christi, Texas. These data suggest that EN is a significant allergen in urban communities. Allergenic proteins occur in both spore and mycelium, suggesting that both must be included in the reagents for skin testing and immunotherapy. PMID- 1629497 TI - Insect-sting challenge in 138 patients: relation between clinical severity of anaphylaxis and mast cell activation. AB - One hundred thirty-eight patients with a previous anaphylactic reaction to a yellow jacket or a honeybee sting, as well as eight volunteers, were subjected to an in-hospital sting challenge. Plasma levels of histamine, tryptase, and prostaglandin D2 (PGD2) during sting challenge were studied in relation to clinical symptoms. Prechallenge levels (mean +/- SD) of histamine, tryptase, and PGD2 were 2 +/- 1 nmol/L, 0.3 +/- 0.3 U/L, and 320 +/- 223 ng/L, respectively. In the volunteers and in none except for one of the nonreacting patients, these levels did not change significantly after challenge. In contrast, mean increases in the group of 18 patients with a mild reaction were significant for histamine and tryptase at one or more time points after the challenge. (Five patients demonstrated no increase in histamine; nine demonstrated no increase in tryptase.) Except for histamine levels in one patient, these increases were considerably more in all 17 patients with a severe reaction, starting from the first anaphylactic symptoms. Fifteen minutes later, peak values were reached of 1275 +/- 2994 nmol of histamine per liter (range, 3 to 12800 nmol/L; median, 11 nmol/L) and 406 +/- 1062 U of tryptase per liter (range, 1.8 to 4400 U/L; median, 17 U/L). This rise in levels inversely correlated with the mean arterial pressure. Plasma levels of PGD2 in severely reacting patients did not differ significantly from those in patients with a mild or no reaction. In conclusion, only 28% of patients with a history of Hymenoptera anaphylaxis developed an anaphylactic reaction after an in-hospital challenge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629498 TI - An approach to immunologic reactions associated with plasma exchange. AB - Immunologically mediated anaphylactic-type events are not uncommon with PE. The pathogenesis of these reactions is not well understood and demands further investigation. If a technique or equipment-related phenomenon can be identified, it should be addressed (e.g., replace the membrane for a more biocompatible membrane and use better rinsing procedures to eliminate ethylene oxide). Testing for specific relevant immunogen, either by in vivo or in vitro methods, if these methods are available, should be considered. If infusion of essential blood products is the most likely cause, then a premedication regimen may be helpful in preventing such reactions. As the risks and benefits of treatment are weighed, it is important to remember that every hive need not be eliminated. Instead, the goal is to prevent compromise to oxygenation and perfusion in both mother and fetus while comfort is maintained and drug-induced adverse effects are avoided. PMID- 1629499 TI - Ambophyllin, an office-dispensed tablet for asthma, contains triamcinolone. PMID- 1629500 TI - Proteinases in extracts of the storage mite, Aleuroglyphus ovatus. PMID- 1629501 TI - Increased concentrations of airborne grass allergen during lawn mowing. PMID- 1629502 TI - Allergenicity screening of "hypoallergenic" milk-based formulas. PMID- 1629503 TI - Reducing domestic exposure to dust mite allergen reduces bronchial hyperreactivity in sensitive children with asthma. PMID- 1629504 TI - Morrow Brown needle facts. PMID- 1629505 TI - Do the group II dust mite allergens correspond to lysozyme? PMID- 1629506 TI - Long-term comparison of three combinations of albuterol, theophylline, and beclomethasone in children with chronic asthma. AB - Three combination regimens, (1) inhaled albuterol (ALB) with oral theophylline (THEO), (2) inhaled ALB with inhaled beclomethasone dipropionate (BDP), or (3) inhaled ALB, inhaled BDP, and oral THEO, were evaluated and compared as optimal pharmacotherapy for chronic asthma in 111 children. In this double-blind, parallel-group, multicenter study, children, aged 6 to 16 years with moderately severe asthma (unstable despite daily medications), were treated with one of the combinations for 12 weeks. Patients were evaluated every 4 weeks by spirometry and serum THEO measurement. Patients kept daily symptom diaries, measured peak flow rates twice daily, and recorded adverse events. Treatment groups did not differ in disease or demographic characteristics at study entry. All three combination treatments provided and maintained significant improvement in FVC, FEV1, and FEF25%-75% volume points, and compared with that of pretreatment, with no significant differences between treatments. Throughout the 12-week treatment period, however, patients receiving BDP had lower symptom scores, fewer had more than one asthma attack, fewer required "bursts" of prednisone (p = 0.001), and fewer required rescue medication (p = 0.009). Significantly more patients receiving BDP said that they felt better than they did at the beginning of the study compared with the number of patients not receiving BDP (p = 0.002). Adverse events were similar among treatment groups. PMID- 1629507 TI - A comparative study of the effects of an inhaled corticosteroid, budesonide, and a beta 2-agonist, terbutaline, on airway inflammation in newly diagnosed asthma: a randomized, double-blind, parallel-group controlled trial. AB - We compared the effect of an inhaled corticosteroid, budesonide, and an inhaled beta 2-agonist, terbutaline, on clinical symptoms, lung function, and airway inflammation in 14 adult patients with newly diagnosed asthma. The study was conducted as a randomized, double-blind, parallel-group trial. Seven patients inhaled 600 micrograms, twice daily, of budesonide, the other seven patients inhaled 375 micrograms, twice daily, of terbutaline via identical metered-dose inhalers with a spacer. Bronchial biopsy specimens, obtained before randomization and after 3 months of treatment, were analyzed by electron microscopy. Both groups improved clinically budesonide was more effective than terbutaline in improving morning and evening peak expiratory flow rates, as well as bronchial responsiveness to inhaled histamine. Treatment with budesonide was accompanied by increased numbers of ciliated airway cells and intraepithelial nerves and fewer inflammatory cells, including eosinophils, especially in the epithelium, these changes were not observed in specimens from terbutaline-treated patients. We conclude that, in contrast to inhaled terbutaline, inhaled budesonide improved lung function and bronchial hyperreactivity in adult subjects with asthma treated for 3 months and that this corticosteroid was more effective in ameliorating abnormalities of the bronchial epithelium and decreasing inflammation in the airways. PMID- 1629508 TI - Biochemical variability of venoms from individual European and Africanized honeybees (Apis mellifera). AB - To study biochemical differences between venom from individual honeybees, venom sacs from 103 European (EU) bees and 92 Africanized bees representing 12 different colonies were dissected, and the dry weight (DW) of venom from each bee was determined. Venom from each of these bees was studied with isoelectric focusing and functional assays for phospholipase A2 and melittin. Phospholipase concentrations in individual EU bee venoms varied between 1.8% and 27.4% (wt/wt). The melittin concentration in EU bee venom varied less and, on the average, was found to be much lower than previously reported. There was an eightfold to ninefold difference between lowest and highest venom sac DW contents, suggesting the possibility of highly variable venom delivery from bee stings. One EU bee contained greater than 300 micrograms of venom, three times the recommended maintenance dose for venom immunotherapy. Isoelectric focusing also demonstrated large differences between individual bees, with respect to major and minor components of their venoms. Africanized bees contained significantly less venom but more phospholipase than did EU bees. Bee venoms from different colonies differed in their DW content and in their concentrations of phospholipase and melittin. The results are relevant to the uncertainty of responses from sting challenges and field stings in allergic patients and massive stinging attacks on normal subjects. PMID- 1629509 TI - Outcome of short-term hospitalization for children with severe asthma. AB - This study presents results of a family-centered, short-term residential program in which medical, behavioral, and treatment assessments were provided to the child with severe asthma and the family. After a median stay of 15 days, forty four consecutively admitted children with severe asthma achieved a 93% reduction in hospital days (median, 7 hospital days for the year before treatment versus median 0 hospital days per patient per year at 20 1/2-month follow-up; p less than 0.001) and an 81% reduction in emergency care (median, 4 visits for the year previously versus median, 0.4 visits per patient per year at follow-up; p less than 0.01). There was also a significant reduction in corticosteroid bursts and improvement in FEV1. Unique to this program was mandatory family participation focusing on the child's and family's adaptation to severe asthma and development of family-specific interventions to promote compliance with the treatment regimen. Child and family functioning was assessed at admission and follow-up. Hospital use at follow-up was greater for children from dysfunctional families. Families demonstrating difficulties in disciplining the child with asthma required more hospital days both before admission and at follow-up. Short-term hospitalization for children with severe asthma is associated with significant improvement in pulmonary morbidity when the family of the child is included in assessment and treatment. PMID- 1629510 TI - The nasal response to histamine challenge: effect of the pollen season and immunotherapy. AB - To evaluate changes in the nasal response to histamine, we challenged 19 subjects with allergic rhinitis caused by ragweed (RW) before, during, and after the RW season with increasing doses of histamine diphosphate. We compared their response, as measured by symptoms and the levels of TAME-esterase activity and albumin recovered in the nasal lavage fluid, with response of two groups with allergic rhinitis undergoing immunotherapy with moderate-dose (N = 16) and high dose (N = 11) RW (2 and 24 micrograms of antigen E [Amb a I] as maintenance dose, respectively). Four challenges with histamine were performed in each group: before, at the peak of, near the end of, and 2 weeks after the RW season. The three groups of subjects had similar skin sensitivity to antigen and levels of TAME-esterase activity and albumin recovered from nasal lavages after histamine challenge performed before seasonal exposure. Symptom diaries obtained throughout the season revealed a significant reduction only in the high-dose immunotherapy treated group. At the peak of the season, the untreated group had more symptoms in response to the challenge compared with the challenges before and after the season (p = 0.04 for both groups). The saline challenge occurring before challenging with histamine also demonstrated a significant increase at the peak of the season compared with increases before the season (p = 0.02). This observation was also true for the levels of albumin and TAME-esterase activity. If the response after saline challenge was subtracted from each response after histamine challenge, no difference was found in the results between any of the visits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629511 TI - Promotional activities of the non-genotoxic carcinogen bemitradine (SC-33643). AB - Bemitradine (SC-33643), a diuretic antihypertensive agent, was studied for its carcinogenicity in a 2-year bioassay in Charles River CD rats via dietary admix at dosages of 50, 150 and 450 mg kg-1 for up to 97 weeks (after which they were followed for eight additional weeks without treatment). Body weights were decreased compared to controls: 5-15% in the female and 10-12% in the male dosage groups by week 105 of the study. Prolactin values were significantly increased in 150 and 450 mg kg-1 females. The compound caused significant increased incidences of liver, thyroid (both sexes) and mammary (females only) neoplasms. The metabolism of bemitradine was studied in both rats and man. Bemitradine and its primary metabolite (SC-36741; desethylbemitradine) were tested and found to be non-genotoxic in Ames, rat primary hepatocyte UDS, CHO/HGPRT, CHO cytogenetics, in vivo mouse micronucleus and mouse lymphoma TK+/- (bemitradine only) assays. Finally, in an altered hepatic foci (Y-glutamyl transpeptidase positive) promotion assay in female Charles River CD rats, bemitradine was found to be a promotor, though not as potent as phenobarbital. We concluded that bemitradine (which has been dropped from development) is a non-genotoxic carcinogen which appears to act by a hormonally modulated promotional activity in inducing tumors in the liver and mammary glands. Tumors seen in the thyroid were probably secondary to the effects of bemitradine on metabolism. PMID- 1629512 TI - Flow cytometry, morphometry and histopathology as biomarkers of benzo[a]pyrene exposure in brown bullheads (Ameiurus nebulosus). AB - Brown bullheads were given a single intraperitoneal dose of 0, 5, 25 or 125 mg kg 1 benzo[a]pyrene (BaP), a carcinogenic polycyclic aromatic hydrocarbon, and evaluated over 18 months. Flow cytometric analyses of hepatocyte DNA content indicated an increase in DNA synthesis in BaP-exposed fish prior to day 14 post exposure. Thereafter, all flow cytometric variables returned to initial levels. Histopathological evaluation of livers from fish sampled at 18 months revealed significant differences among treatments in the amount of hepatic macrophage ceroid pigmentation and basophilic staining intensity. No neoplasms or changes in blood cell DNA content were detected. Significant morphometric variations existed among fish, but differences between sexes overshadowed differences attributable to dose. Flow cytometry yielded no evidence of long-term DNA alterations from a single exposure to BaP; however, the differences detected by DNA analysis shortly after the toxic event suggest that flow cytometric cell cycle analysis may be useful for documenting continuing exposures. PMID- 1629513 TI - Embryolethality and teratogenicity of butyl benzyl phthalate in rats. AB - Pregnant Wistar rats were given butyl benzyl phthalate (BBP) at a dose of 2.0% in the diet on days 0-20, days 0-11 or days 11-20 of pregnancy. Food consumption and body weight gain were decreased in pregnant rats given BBP. Pre-implantation loss in the BBP-treated groups was comparable to that in the control and pair-fed groups. All dams given BBP on days 0-20 or days 0-11 exhibited complete resorption of all the implanted embryos. No increase in post-implantation loss was found in pregnant rats given BBP on days 11-20. Marked teratogenicity was detected in fetuses of the dams given BBP on days 11-20. Cleft palate and fusion of the sternebrae were predominantly observed. Seventy-two of the 134 fetuses had a cleft palate. The incidence of malformations in this group was significantly and markedly higher than that in the control and pair-fed groups. In conclusion, the administration of BBP during the first and second half of pregnancy produced embryolethality and teratogenicity, respectively. PMID- 1629514 TI - Tannin content of tea and coffee. AB - The tannin content of over-the-counter Indian tea, of green coffee beans and of the roasted coffee beans prepared from the same green beans was determined with a radial diffusion-protein precipitation technique and with a spectrophotometric method. The green beans contained 6.6 +/- 0.6 mg g-1 weight tannic acid equivalents as found by protein precipitation (n = 5, +/- SD) or 6.8 +/- 2.3 mg g 1 by spectrophotometry. The same figures for roasted beans were 18 +/- 1.7 and 17 +/- 2.7 mg g-1, respectively. Tea contained 37 +/- 2.6 mg g-1 weight tannic acid equivalents as analysed by spectrophotometry and 24 +/- 2.8 mg g-1 by the protein precipitation technique. The latter finding may show that the biological reactivity of tannins is variable, although no major changes in the tannin precipitated albumin occurred as shown by electrophoretic analysis. Both methods provide an easy analysis of the reportedly carcinogenic plant tannins. PMID- 1629515 TI - Comparative lethality of methanol, ethanol and mixtures in female rats. AB - The lethalities of pure methanol and pure ethanol were compared to two mixtures of ethanol/methanol with the following percentages (95/5% and 65/35% v/v). This study was conducted to simulate situations of human exposure to denaturated alcohol (by 5% methanol) or adulterated alcohol (by 35% methanol). Four groups of female adult virgin albino rats were treated with the four mixtures. A fifth group was used as a vehicle control. Graded oral doses were given to eight animals per dose. Lethality over 24 h was used as an end-point. The LD50 was calculated for each of the four treatments on a molar basis. A dose-response function for each mixture was plotted of percentage lethality vs. mmol kg-1 equivalent to the given ml kg-1 dose. Results showed a significantly different LD50 estimates (P less than 0.03) for the four mixtures. The order of lethal toxicity was as follows: 95/5% methanol/ethanol, pure methanol, pure ethanol then 65/35% methanol/ethanol. Slope comparisons indicated two pairs: 65/35% ethanol/methanol and pure ethanol yielding a steep slope, and 95/5% ethanol/methanol and pure methanol yielding a shallow slope. These data indicated that the acute lethality of ethanol/methanol mixtures is a complex unpredictable function. This toxicity presumably depends in a complicated way on the differences in the effective molecular weights of the two alcohols in each of the mixtures. PMID- 1629516 TI - Indirect and lactation-associated changes in renal alkaline phosphatase of newborn rats prenatally exposed to cadmium chloride. AB - Pregnant Sprague-Dawley rats were intraperitoneally injected with physiological saline solution (vehicle) or cadmium chloride (CdCl2) at 2.5 mg kg-1 body wt. on days 8, 10, 12 and 14 of gestation. Offspring were examined for renal alkaline phosphatase activity (ALP) on postnatal days (PND) 3 and 12, and for kidney metallothionein (MTh) and for liver, kidney and entire gastrointestinal tract 109Cd content at birth and on PND 3 and 12. No effects were observed on neonatal survival or on body, liver and kidney weights of pups up to PND 12. Newborns born and fed by mothers exposed to CdCl2 during pregnancy exhibited a significant decrease in ALP activity on PND 3. Conversely, no significant changes were observed in newborns lactated by surrogate non-treated mothers. Renal MTh increased with age but was not influenced by maternal treatment. Traces of 109Cd were present in the liver at birth (5-7 ng). Thereafter, 109Cd was mainly found in the gastrointestinal tract of newborns lactated by their biological mothers (610-690 ng on PND 12), with a marginal uptake in the liver (10-12 ng on PND 12). 109Cd was not detectable in the kidneys at any age (less than 4 ng). These results show that prenatal exposure to Cd cannot be the sole aetiological agent in the induction of the subtle and transitory changes in renal biochemistry observed in offspring born and fed by female rats intraperitoneally injected with 2.5 mg CdCl2 kg-1 body wt. on days 8, 10, 12 and 14 of gestation. The results also contradict the role of a direct effect on the kidney. PMID- 1629517 TI - Renal effects of N-(3,5-disubstitutedphenyl)-succinimides in the Fischer 344 rat. AB - Previous studies have demonstrated the importance of substitution at the 3- and 5 positions of the phenyl ring in N-phenylsuccinimides for the production of nephrotoxicants in this series of compounds. The purpose of this study was to determine if the electronic nature of the 3,5-substituents is an important determinant for nephrotoxic potential. Male Fischer 344 rats (four rats per group) were administered a single intraperitoneal injection of a succinimide (0.4 or 1.0 mmol kg-1) or vehicle, and the renal function was monitored for 48 h. Only N-(3,5-dichlorophenyl)succinimide (0.4 or 1.0 mmol kg-1) induced marked changes in renal function. Urine volume, BUN concentration and proteinuria were increased following N-(3,5-dinitrophenyl)succinimide (1.0 mmol kg-1) treatment but other renal parameters and renal morphology were unchanged in this treatment group. These results indicate that the presence of halogen atoms at the 3- and 5 positions of the phenyl ring in N-phenylsuccinimides is more important for nephrotoxic potential than the presence of non-halogen substituents. The reason why halogen substitution is an important determinant for N-phenylsuccinimide nephrotoxicity is unknown. PMID- 1629518 TI - The local lymph node assay: results of a final inter-laboratory validation under field conditions. AB - The local lymph node assay (LLNA) assesses the sensitizing activity of chemicals by measurement of primary lymphocyte proliferation in lymph nodes draining the site of application. In this final inter-laboratory study the consistency of LLNA results between laboratories and with guinea pig maximization test (GPMT) data was examined under 'field' conditions. Nine chemicals were evaluated independently by each laboratory according to guidelines for test concentration and vehicle selection developed during previous validation studies to ensure assay optimization. Equivalent predictions of sensitization potential were obtained by all laboratories for eight chemicals. Five of seven chemicals identified as sensitizers in the GPMT were correctly identified in the LLNA--four by all laboratories and 1 (4-chloroaniline) by one laboratory only--although in this latter case, two other laboratories obtained clear dose responses, suggestive of sensitization. The LLNA identified correctly those chemicals predicted to be extreme or strong sensitizers in the GPMT. The remaining two chemicals were non-sensitizers in the guinea pig and failed to elicit positive proliferative responses in the LLNA. These data demonstrate that sensitivity and reliability of the LLNA is retained when chemicals are evaluated independently, and that it provides a reliable pre-screen for the identification of chemicals with significant sensitization potential. PMID- 1629519 TI - Distribution to the fetus and major organs of the rat following inhalation exposure to pyrene. AB - Concentrations of pyrene and total metabolites were determined for individual fetuses and selected maternal organs and tissues immediately and 6 h following a 95-min head-only exposure of pregnant Wistar rats, on gestation day 17, to five levels of pyrene over the range 200-800 mg m-3 as a microcondensation aerosol. The influence of uterine horn, side and position, on distribution to the fetus was assessed. The concentration of both pyrene and its metabolites increased more over the exposure range (eightfold) than did those in the fetus. Concentrations of pyrene or its metabolites in fetal tissues were not found to be related to its position on the uterine horn. There was an unexplained and significant (P less than 0.01) higher concentration of pyrene in fetuses on the right side relative to the left side of the uterine horn for the animals killed immediately following exposure. A comparison of the levels in maternal tissues measured immediately following the exposure and 6 h later showed that there was some redistribution of pyrene and its metabolites to the fat tissues, i.e. levels in the fat increased over the 6 h period following the exposure. Levels in the other tissues diminished during this period. In general, concentrations of pyrene and its metabolites were lowest in the fetal tissues relative to those in the sampled maternal organs and tissues. PMID- 1629520 TI - Arterial baroreflexes are not essential in mediating sympathoadrenal activation in conscious endotoxic rats. AB - We examined the contributions of arterial baroreceptor reflexes in mediating sympathoadrenal activation during endotoxicosis. Conscious rats with chronic sinoaortic denervation (SAD) or sham-operation (SHAM) were subject to endotoxin treatment (5 mg/kg, i.v.). Hemodynamic responses, renal sympathetic nerve activity (RSNA) and plasma catecholamines were assessed at different times post endotoxin infusion. In both SAD and sham groups, intravenous endotoxin injection induced a rapid and significant sympathoadrenal activation, as indicated by a parallel elevation of RSNA and plasma catecholamines. Such activation peaked 15 30 min following endotoxin and was sustained throughout the 2-3 h protocol. The early response of the sympathoadrenal system to endotoxin is more profound in SAD rats compared to sham rats. We propose that the afferent neural input from arterial baroreceptors is not essential in mediating sympathoadrenal activation during sepsis. The elimination of feedback buffering mechanisms with SAD may account for the augmented sympathetic response seen in SAD animals. PMID- 1629521 TI - Inhibitory effect of noradrenaline on acute liver injury induced by carbon tetrachloride in the rat. AB - The effect of exogenous noradrenaline (NA) on acute liver injury was investigated in rats receiving a single dose of carbon tetrachloride (CCl4). Animals were divided into the following groups: (I) no treatment, used for plasma catecholamine assay; (II) received CCl4 only; (III) treated with CCl4 plus noradrenaline (NA). Plasma levels of catecholamine (CA) were elevated in both groups II and III, particularly in NA: average value at 33 h after the exposure of CCl4 increased to 290-fold of the control in group II and to 513-fold in group III. Subsequently, the levels of NA decreased with time, and were comparatively well-preserved in the rats of group III. Hepatic changes observed in the animals of group II were as follows: destruction with reduced number in rough endoplasmic reticulum; destruction and disappearance of cristae in mitochondria, and numerous fat droplets (shown by electron microscopy); histologically observed marked centrilobular necrosis with steatosis followed by progression with time; and microangiographically demonstrated deranged intrahepatic microvasculature. By contrast, these changes were successfully prevented by NA treatment (group III). Furthermore, histologically observed centrilobular change was restored with time. It was concluded that, in a deranged state, NA takes a form quite dissimilar to ordinary state: Na exerts for hapatoprotective and is highly involved in liver injury. PMID- 1629523 TI - Autonomic cardiovascular reflexes in progressive supranuclear palsy. AB - Assessment of possible autonomic nervous system dysfunction was performed by testing cardiovascular reflexes in nine patients with progressive supranuclear palsy (PSP). The patients were significantly different from 15 control age matched subjects because of greater blood pressure drop on standing for 1 min, diminished rise of diastolic blood pressure during the sustained handgrip test, and lack of compensatory tachycardia measured by the 30:15 ratio on standing. The latter test abnormality was caused by a slow rise to erect posture. No differences were observed in the cold pressor test, Valsalva ratio, and heart rate response to deep breathing. The differences between patients and control subjects were usually small. Autonomic nervous system involvement in patients with PSP is minor and is caused by involvement of central brain stem sympathetic nuclei or efferent fibers. PMID- 1629522 TI - Salivary secretion elicited by activation of the parabrachial nuclei in the cat. AB - The lateral pontine tegmentum contains the parabrachial nuclei (NPB) which have been identified as a relay nucleus for cardiovascular, respiratory and gustatory systems, but their role in the regulation of these systems is not well understood. We examined the effects of electrical and chemical stimulation of the NPB on blood pressure, phrenic and hypoglossal nerve activity and salivary secretion. These variables were measured in eight anesthetized (alpha chloralose/urethane, 30/150 mg/kg, n = 5) or decerebrate (n = 3) cats before, during, and after trains of electrical stimulation (1 ms pulse duration, 10 Hz 5 min train duration, currents as low as 10 microA) delivered unilaterally to NPB. Stimulation of the NPB elicited copious salivary secretion (1100 +/- 270 mg, mean +/- S.D.; P less than 0.001). Secretion was blocked completely by prior administration of atropine. The effects of the stimulus train on the respiratory and cardiovascular systems were variable and inconsistent even though short latency responses of phrenic and hypoglossal nerve activities to single pulses were consistent. The short-latency response of phrenic nerve activity was biphasic, a decrease followed by an increase in activity; the response of hypoglossal nerve activity was monophasic, a transient increase in activity. Effects of electrical stimulation were replicated by the injection of an excitatory amino acid agonist (kainic acid) into the dorsolateral pons. Injection of 50 nl of 10 mM kainic acid into the NPB evoked salivary secretion, indicating that this response was elicited by stimulation of cell bodies in the region. In addition, chemical excitation increased breathing frequency, peak phrenic nerve activity, and blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629524 TI - Postnatal development of noradrenaline-containing nerves of the rat uterus. AB - The postnatal development of noradrenaline (NA)-containing nerves of the rat uterus and its associated blood vessels was investigated using histochemical and biochemical methods. These studies were carried out in conjunction with examination of the morphology of the uterus and the density of blood vessels at the prepubertal, peripubertal and adult stages. It was demonstrated that: (1) the rat uterus is innervated at birth; (2) the innervation of blood vessels develops earlier than that of the myometrium and the density of NA-containing perivascular nerves is not affected by puberty; (3) between birth and day 30 (prepubertal) there was a progressive increase in the innervation of the myometrium which was accompanied by a progressive increase in the total NA content of the organ; (4) at the first oestrus there was a marked increase in the weight of the uterus and isolated myometrial and parametrial tissue. Both muscle cell size and number were also increased. The density of myometrial innervation by NA-containing nerves was markedly reduced, although the total NA content did not change at this stage. This indicates a 'dilution' of myometrial NA-containing nerves in a greater amount of non-neuronal tissue; and (5) between the peripubertal and adult stages there was a further increase in uterine weight together with an increase in the number of smooth muscle cells and a reduction in the density of myometrial NA containing nerves. Although the density of perivascular nerves was unaffected by puberty, the number of blood vessels supplying the uterus increased during the transition to the adult stage. This was reflected by a significant increase in the total NA content of the uterine horn and of isolated myometrial and parametrial preparations. PMID- 1629525 TI - Comparison of locations and peptide content of postganglionic neurons innervating veins and arteries of the rat hindlimb. AB - The ganglionic location of hindlimb vasoconstrictor sympathetic neurons in several species is known but the locations of neurons innervating limb arteries or veins, specifically, have not been compared and neurochemical differences between them have not been examined in detail. This study was designed to determine whether neurons innervating arteries and veins are organized as distinct populations and whether neurons innervating arteries, veins or footpads contain the same peptides. Retrograde transport of fluorescent dyes was used to identify, separately, paravertebral postganglionic neurons in the 13th thoracic to 6th lumbar (T13-L6) chain ganglia that innervate the femoral arteries, femoral veins and footpads of the rat hindlimb. The proportions of venous and arterial vasomotor neurons and footpad neurons containing neuropeptide Y- and vasoactive intestinal polypeptide-immunoreactivity (NPY-Ir, VIP-Ir) were then compared. Venous vasomotor neurons were found mostly (62%) in the L1 and L2 ganglia. The majority of arterial vasomotor neurons (81%) were distributed slightly more caudally in L1-L3. Veins and arteries were not innervated by the same cells. Footpad neurons were located mostly in L4-L6. NPY-Ir was identified in 17% of the venomotor neurons, in 94% of arterial neurons and in 24% of footpad neurons. VIP Ir was found in 3% of the venomotor neurons, 8% of the arterial neurons and in 44% of the footpad neurons. In conclusion, hindlimb venous and arterial vasomotor neurons are anatomically distinct, are mixed randomly within the chain ganglia and differ markedly in their content of NPY, consistent with reported differences in neuromuscular transmission to arteries and veins. The most likely hindlimb postganglionic neurons to contain VIP were those innervating footpads, probably controlling sweat gland function. PMID- 1629526 TI - The reflex bradycardia evoked by brain ischemia and its relation to aortic A- and C-fiber baroreceptors. AB - In urethane-anesthetized rabbits with the right aortic nerve (RAN) sectioned, we examined the reflex heart rate (HR) responses during brain ischemia for approximately 30 s, by applying the anodal block to the unsectioned left aortic nerve (LAN) and, subsequently, by denervating the LAN. The maximum decreases in HR occurred at around 30 s after the onset of brain ischemia. The anodal block used in this study selectively inhibited the aortic A-fiber conduction but did not inhibit the volley of aortic C-fibers. The maximum HR fall responses to brain ischemia with and without the anodal block were 143 +/- 7 and 183 +/- 7 beats/min, respectively. When the maximum value of HR fall during brain ischemia in the absence of aortic nerve signals was subtracted from these two values, the reflex HR fall responses to brain ischemia with aortic C and A baroreceptor activation were 98 +/- 7 and 43 +/- 8 beats/min, respectively. In another series of experiments used for the same techniques, the reflex fall in HR seen during brain ischemia with the anodal block was totally abolished by vagotomy. The results indicate that the ability of aortic C baroreceptors becomes more prominent on the magnitude of brain ischemia-induced reflex bradycardia as compared to that of aortic A baroreceptors. PMID- 1629527 TI - Long-term care choices for geriatric residents. AB - Nursing home residents have been customarily excluded from participating in making decisions about their own care. However, gerontological nurses have demonstrated that giving residents choices about their daily activities enhances resident independence and self-esteem. Study results indicate that residents in long-term care facilities are not receiving opportunities to make choices about their daily activities as often as choices are made for them. Many of the choice giving behaviors did not take any more of the caregiver's time. The study assumed that choices about daily activities, dressing, and group participation were important to residents. Future study should include a survey of residents to determine what type of choices are important to them. Residents could be asked to prioritize activities that they would most like to have a choice about. PMID- 1629528 TI - Patients with dementia involving families to maximize nursing care. AB - Incorporating family members in the care of patients with dementia provided pertinent psychosocial data, led to mutual decision-making regarding care, and produced changes in the responses of the residents with dementia, as well as in the family and nursing staff. The experimental group experienced increases in psychosocial nursing diagnoses with planning and interventions to meet the problems, more extensive problem description, and an active focus on interaction and change in the nurse's notes. As a result of collaborative nursing and family involvement, personal articles were brought from home; family collateral visits and interaction increased; families were more involved in the unit, medical center, and support groups; and p.r.n. medication use was decreased. As health care technology prolongs the life of patients with chronic illness and sequelae such as dementia, nurses will need to continue to include families as collaborators in providing quality care. PMID- 1629529 TI - Geriatric nursing in the baccalaureate curriculum. AB - Increased gerontological nursing content is needed in the curriculum of schools of nursing because of a dramatic increase in the number of older persons, many of whom will need specialized health care. A review of the gerontological nursing content in the current courses of a college of nursing led to specific recommendations for change and additions to the curriculum. A published list of suggested gerontological nursing content was used as a guide to determine which topics needed to be integrated into the curriculum. An ongoing evaluation of the curriculum is needed to determine the appropriateness of the content changes and to determine if students perform better as a result of these changes. PMID- 1629530 TI - Musical debate. PMID- 1629531 TI - Patients in acute care settings. Which health-care services are provided? AB - Studies have shown that early discharge planning, multidisciplinary care, and a focus on functional abilities for older adults do reduce acute care hospital readmissions. Of the 101 records reviewed of acute care admissions 75 years of age and older, 36 had no multidisciplinary service documented and 75 had no discharge planning documented within 48 hours of admission. Eleven functional activities were assessed and documented in one record with a range of 4 to 11 activities assessed in the remaining 100 documents. Identifying and filling gaps in care provided to this age group might provide substantial cost savings, improve care, and decrease complications. Advocacy, coordination of care, and greater knowledge may be keys to narrowing these service gaps. PMID- 1629532 TI - Focusing on dementia. PMID- 1629533 TI - Artificial nutrition and hydration. PMID- 1629534 TI - A matter of choice. PMID- 1629535 TI - Discharge planning predicting patients' needs. AB - The elderly are at higher risk for longer and more frequent lengths of hospital stay than other adults. Comprehensive discharge planning programs, including early identification of those at risk, can alter these statistics. Screening inventories to identify patients at risk have been available for many years, but they are not specific to the needs of the elderly. The Blaylock Risk Assessment Screen (BRASS) is administered on admission and identifies patients at risk for prolonged hospital stay and in need of discharge planning resources. The nurse can use the data BRASS provides to improve care outcomes while the patient is in the hospital and in the transition to home care. It shows promise for use as the first phase of a discharge planning program. PMID- 1629536 TI - The pursuit of happiness. PMID- 1629537 TI - Trapeziometacarpal osteoarthritis: surgical technique and results of "stabilized resection-arthroplasty". AB - Since 1973, 212 hands of 179 patients with disabling trapeziometacarpal osteoarthritis were treated with resection-arthroplasty stabilized by capsuloplasty and intermetacarpal ligament construction; 159 patients (180 hands) could be followed up (average, 7.8 years; range, 1 to 17.3 years). Pain relief was excellent in 89%, good in 10%, and fair in 1%. Patients were "delighted" (78%), "satisfied" (18%), "indifferent" (2%), or "disappointed" (2%) with their functional results. Palmar abduction improved 25%. The tip of the thumb reached the fifth metacarpophalangeal joint in 97% of the hands. Grip strength improved 29%; key pinch, 19%; pulp pinch, 24%. First metacarpal was stable in 94% of the cases. Scaphometacarpal space averaged 5.5 mm. There were three complete failures (2%); complications were mild and infrequent. Because of its good, predictable results, "stabilized resection-arthroplasty" is our preferred surgical treatment for osteoarthritic trapeziometacarpal joints. PMID- 1629538 TI - Trapeziometacarpal joint arthrodesis: a functional evaluation. AB - Over a 10-year period, 39 trapeziometacarpal (TM) joint fusions were performed in 37 patients. Pin fixation was used in 27 fusions and staple fixation in 12; all were bone grafted. There were five delayed unions (greater than 3 months) and three nonunions. Twenty-four fusions were evaluated at an average of 4 years. Subjectively, there were 11 excellent, 7 good, 5 fair, and 1 poor result. Grip and pinch strength were symmetrical, and the nine-hole peg test (a measurement of dexterity) was slightly better on the treated side. X-ray films were taken and compared with 25 normal films to assess metacarpal mobility. There was a 72% reduction in the adduction/abduction arc and a 61% reduction in the flexion/extension arc. Despite the marked decrease in motion, subjective functional complaints were minimal. X-ray films were evaluated independently by a radiologist to assess progression of degenerative changes. Only two patients were noted to have changes at the scaphotrapezial joint. PMID- 1629539 TI - Long-term follow-up of trapeziometacarpal arthroplasty with coexisting scaphotrapezial disease. AB - Visualization of the scaphotrapezial joint during basal joint arthroplasty has been recommended to establish the stage of degeneration. This study attempts to clarify that recommendation and evaluate whether moderate wear of the joint precludes a good result of trapeziometacarpal hemiarthroplasty. To assess the need for inspection of the scaphotrapezial joint, x-ray films, tomograms, and operative findings in 23 cases of basal joint arthroplasty were reviewed. X-ray findings agreed with operative findings at the scaphotrapezial joint in only 76% of the cases. We also evaluated 18 thumbs in 15 patients who underwent interposition arthroplasty of the trapeziometacarpal joint and at surgery had moderate degenerative changes of the scaphotrapezial joint. The scaphotrapezial joints were left intact and the trapeziometacarpal joints were reconstructed. Follow-up averaged 8 years. In no case was there x-ray or symptomatic progression of the disease at the scaphotrapezial joint. Clinically, 78% were rated excellent, 17% good, and 5% fair. PMID- 1629540 TI - The prevalence of carpal tunnel syndrome in patients with basal joint arthritis of the thumb. AB - Basal joint arthritis of the thumb and carpal tunnel syndrome are common conditions with an acknowledged coexistence. This article attempts to quantify the prevalence of carpal tunnel syndrome in patients with basal joint arthritis and to examine some of the etiologic factors that affect the coexistence of the two disorders. Of 246 patients who had surgery about the basal joint, 95 patients (39%) were identified by chart review as having carpal tunnel syndrome. Eleven of 122 remaining patients contacted had symptomatic carpal tunnel syndrome confirmed by nerve-conduction studies, bringing the total to 106 (43%). The prevalence was higher in worker's compensation patients and those with diabetes mellitus. The prevalence was lower in men than in women, and patients with inflammatory joint disease were at less risk than those with osteoarthritis. Given this high association, great care should be taken to diagnose or exclude coexistent carpal tunnel syndrome in patients scheduled for basal joint surgery so that, if present, it can be treated at the same time, diminishing the risk of postoperative morbidity and delayed symptoms. PMID- 1629541 TI - Thermographic observations in unilateral carpal tunnel syndrome: report of 61 cases. AB - This study was undertaken to assess the sensitivity and specificity of thermographic diagnosis of unilateral carpal tunnel syndrome in a patient population large enough to permit meaningful statistical analysis. Sixty-one persons with clinical diagnoses of unilateral carpal tunnel syndrome confirmed by electrodiagnostic examination and 40 symptom-free volunteers underwent standard thermographic examinations. The thermographic images were then randomly sorted and interpreted by an experienced physician thermographer. Fifty-seven of the 61 patients with carpal tunnel syndrome were found to have thermographic abnormalities, while only one of the control group was found to have such an abnormality. Individual area sensitivity was highest in the dorsal area, but addition of other regions increased this measure; specificity ranged between 98% and 100%. These findings would appear to confirm the value of thermography in the diagnosis of unilateral carpal tunnel syndrome. PMID- 1629542 TI - Factors that determine reexploration treatment of carpal tunnel syndrome. AB - Eighteen patients (20 hands) underwent reexploration of the carpal tunnel after a primary carpal tunnel release. The patients complained of unrelieved symptoms after their initial surgical procedures. We recommend reexploration for patients with unrelieved carpal tunnel syndrome if they have a positive Phalen's test, have symptoms that cause nocturnal wakening or are exacerbated by activities, or have a short or transverse initial incision. If the incision is adequate and these symptoms are not present, we believe that reexploration will not result in a satisfactory outcome. PMID- 1629543 TI - Rotary subluxation of the scaphoid resulting in persistent carpal tunnel syndrome. AB - Rotary subluxation of the scaphoid has not been previously reported in the English-language literature as a factor causing persistent or recurrent carpal tunnel syndrome. This report describes a sixty-seven-year-old man with persistent carpal tunnel syndrome. X-ray films showed a scapholunate gap and the scaphoid maintained a flexed position. At surgery the median nerve was found to be fixed to the undersurface of the transverse carpal ligament on the lateral side and was being compressed by the distal pole of the scaphoid. PMID- 1629544 TI - Injection injuries to the median and ulnar nerves at the wrist. AB - Carpal tunnel syndrome is often treated nonoperatively with temporary wrist immobilization and local steroid injections. A direct injection into a peripheral nerve can result in permanent damage. Two cases of median nerve injection injury and one involving the ulnar nerve are presented; all were treated with neurolysis and debridement of the injected material. At follow-up ranging from 1 to 11 years, all patients showed significant improvement, but with some functional loss. The literature is confusing because of the variety of injection techniques used for the treatment of carpal tunnel syndrome, some of which put the median nerve at risk. We recommend that the injection be made midway between the palmaris longus tendon and the flexor carpi ulnaris tendon just proximal to the proximal edge of the transverse carpal ligament in a line with the superficialis tendon of the ring finger. The injection should be stopped and redirected if the patient experiences paresthesia of any kind. PMID- 1629545 TI - The internal anatomy of the median nerve in the region of the elbow. AB - The internal anatomy of the median nerve in the region of the elbow has been studied by microdissection in 20 cadavers. Gross branching patterns were studied in an additional 14 cadavers. There are four major branches or branch groups: I to pronator teres, II to flexor carpi radialis, flexor digitorum superficialis, and palmaris longus; III to the anterior interosseous nerve; and IV to flexor digitorum superficialis. Three of these could be traced proximally within the main trunk of the median nerve, the average being I-10 cm; III-7.5 cm; IV-2 cm. This information should have clinical applications in repair and grafting of the median nerve near the elbow and in understanding clinical nerve compression sydromes. PMID- 1629546 TI - Pisiform-hamate coalition with ulnar neuropathy. AB - Two cases of pisiform-hamate coalition with compression of the ulnar nerve at the wrist are reported. Pisiform-hamate coalition is a rare entity previously thought to be exclusive to West Africans and without clinical significance. These cases occurred in white patients. This is the first description of a carpal coalition resulting in ulnar neuropathy at the wrist. PMID- 1629547 TI - Localized nodular synovitis: a rare cause of ulnar nerve compression in Guyon's canal. AB - A rare case of ulnar nerve entrapment at the wrist by a nodule of localized nodular synovitis is presented. The literature is reviewed with particular reference to the causes of ulnar tunnel syndrome, the uncertainty over the origin of this type of tumor, and its tendency to recur after incomplete excision. PMID- 1629548 TI - Nerve tension and blood flow in a rat model of immediate and delayed repairs. AB - In vivo studies of rat sciatic nerves in models of immediate and delayed repairs demonstrated the viscoelastic properties of the nerve and the inverse correlation between nerve blood flow and tension. In both the proximal and distal segments of the divided nerve in models of immediate and delayed repairs, the nerve blood flow decreased approximately 50% with substantial recovery in 30 minutes after 8% elongation, whereas 15% elongation produced approximately an 80% reduction in blood flow with minimal recovery. However, the baseline blood flow of the nerves in the delayed-repair model was nearly two times higher than that of the acutely injured nerves. Maximal decrease in nerve tension and corresponding increase in blood flow occurred within the first 20 minutes after elongation. The suture pull out with failure of the repairs occurred at more than 15% elongation for all nerves. The previously divided nerves had a sixfold greater decrease in length than the acutely divided nerves (p less than 0.02). For repairs of large nerves where vascular ingrowth is likely to be incomplete, elongation of more than 8% may cause ischemia that is detrimental to nerve regeneration. Mechanical failure of the repairs occurs after elongation of 16% to 17%. The combination of nerve ischemia and mechanical failure of suture repairs suggests that surgeons should be careful to limit the use of elongation in acute and delayed repairs. PMID- 1629549 TI - A new cause of trigger thumb. AB - We report a case of severe painful triggering in the thumb caused by intermittent locking of the interphalangeal joint by a sesamoid bone. The triggering was corrected by excision of the interphalangeal joint sesamoid bone. PMID- 1629550 TI - Adhesions between muscle and bone after forearm fracture mimicking mild Volkmann's ischemic contracture. AB - Five cases of digital flexion contractures after healed forearm fractures were incorrectly diagnosed as mild Volkmann ischemic contractures. All failed to respond to conservative therapy and were considered significant enough to require surgical correction. At surgery, the involved muscle-tendon units were densely adherent to the bone and callus of the fracture site with no evidence of ischemic involvement of the muscle. Lysis of adhesions and lengthening of the contracted muscle corrected the deformities. PMID- 1629551 TI - Elbow flexion contractures treated with serial casts and conservative therapy. AB - We report on the technique of serial casts to successfully reverse elbow flexion contractures in three patients. Patients considered for this technique had a traumatic injury to the elbow that resulted in residual soft tissue restrictions; their mean flexion deformity was 44 degrees, which had been present for an average of 6 months. Treatment consisted of traditional therapy methods to obtain initial stretch and elongation of tissue followed by application of a cylindrical fiberglass cast in the position of maximal elbow extension. The cast was worn for 3 to 5 days, then removed, and the entire process was repeated. After the use of serial casts, elbow flexion contractures were reduced to a mean of 11 degrees. These results have been maintained over an average of 26 months. The use of casts in the treatment of elbow flexion contractures appears to be a viable technique for increasing range of motion when traditional methods of treatment alone are unsuccessful and surgical intervention may be the only alternative. PMID- 1629552 TI - Changes in wrist and forearm configuration with grasp and isometric contraction of elbow flexors. AB - The purpose of this study was to determine the changes in wrist and forearm configuration with grasp and elbow flexor contraction by analysis of resting and grasping x-ray films of 15 normal adults and forearm scanograms of 10 other normal subjects. With grasp, a significant proximal migration of the radius (averaging 0.9 mm), a decrease in the carpal height ratio, and an increase in the lunate uncovering index were observed. With flexor contraction, there was a significant decrease in the forearm interosseous space. PMID- 1629553 TI - Hand reconstruction with allograft demineralized bone: twenty-six implants in twelve patients. AB - A long-term study of 26 phalangeal or metacarpal defects that were reconstructed with allogeneic demineralized bone implants demonstrates healing comparable to that which follows autogenous bone grafting. Average follow-up was 54 months. Five patients had multiple enchondromas (Ollier's syndrome), five children had congenital hand deformities, and all of these had previously had bone grafts harvested for associated craniofacial reconstructions. With the use of demineralized bone implants, tourniquet and operative times were significantly reduced and potential donor site morbidity was eliminated. Further, regional anesthesia was used more frequently and hospitalization time was reduced. There were no postoperative complications. Demineralized bone implants have been particularly useful in patients who previously had refused bone grafting. PMID- 1629554 TI - Salvage in a case of ring avulsion injury with an immediate second-toe wrap around flap. AB - A nonreplantable complete degloving injury to the small finger of a young woman was treated with the immediate microsurgical transfer of a second-toe wrap-around flap. One year after the operation, the donor foot was free of symptoms, and the reconstructed finger had an excellent cosmetic appearance, a range of motion of 0/90 degrees at both the metacarpophalangeal and the proximal interphalangeal joints, and a two-point discrimination of 6 mm. In selected patients, when the degloved skin envelope cannot be revascularized and when the skeletal and tendinous units are still intact, an immediate second-toe wrap-around flap may be a good alternative to amputation. PMID- 1629555 TI - Embryologic development and variations in the anatomy of the ulnocarpal ligamentous complex. AB - Eighteen fetal hand specimens were reviewed in an effort to clarify variations in reports of the ligamentous anatomy of the ulnar side of the wrist. Sizes ranged from 45 mm crown-rump length (CRL) to 325 mm CRL. Representative coronal sections from the 2779 sections available were reviewed. Significant variations in size of triquetral attachment and thickness and consistency of the ulnocarpal ligamentous complex (UCLC) were observed. Each of the specimens exhibited one of four UCLC variations: (1) 5 of 18 (28%) with an average CRL of 187 mm had a dense, thin UCLC, with a focal triquetral attachment; (2) 7 of 18 (39%) with an average CRL of 209 mm had a focal, dense attachment of a thick UCLC to the triquetrum; (3) 5 of 18 (28%) with an average CRL of 220 mm exhibited a thick, dense UCLC with a broad attachment to the triquetrum; and (4) 1 of 18 (5%) with a CRL of 166 mm was unique, with a loose, areolar UCLC broadly attached to the triquetrum. PMID- 1629556 TI - Matched distal ulna resection for posttraumatic disorders of the distal radioulnar joint. AB - In 1985 we published the results of the matched ulna resection in 44 patients, the majority of whom had rheumatoid arthritis. The matched ulna resection maintains the continuity of the distal ulna to the ulnar sling mechanism, including the triangular fibrocartilage complex (TFCC), and resects the distal ulna in a smooth, curved, convex fashion to match the contour of the radius throughout forearm rotation. This article presents the results of the procedure in patients with posttraumatic and mechanical disorders of the distal radioulnar joint. Good to excellent results were noted in 24 of 32 patients. The outcome was related to the severity of the patient's initial problem. PMID- 1629557 TI - Wafer distal ulna resection for triangular fibrocartilage tears and/or ulna impaction syndrome. AB - Partial resection of the distal ulna (wafer resection) has been used to treat patients with symptomatic tears of the triangular fibrocartilage complex or mild ulna impaction syndrome. In this procedure, the distal 2 to 4 mm of the distal ulnar head is resected while preserving the ulnar styloid process and the ligaments attached to it. The triangular fibrocartilage is debrided, repaired, or partially excised as necessary. The procedure is contraindicated if there is more than 4 mm of positive ulnar variance. Thirteen wafer resections of the distal ulna were performed in 12 patients. All had good to excellent results after a minimum follow-up of 1 year. Wafer resection has specific advantages and avoids many of the potential complications of distal ulna recession and ulnar head resection for patients with the conditions described. The procedure is not indicated if instability or degenerative arthritis of the distal radioulnar joint is present or if there is carpal instability. PMID- 1629558 TI - Computerized tomographic evaluation of acute distal radial fractures. AB - To learn whether computerized tomography offered additional useful information over conventional radiographic evaluation of acute distal radial fractures in the younger adult, we scanned 22 consecutive injured wrists. Of the distal radial fractures in 19 wrists, sixteen were defined on plain films as intra-articular. In contrast, computerized tomography demonstrated that all fractures of the distal radius had intra-articular extension. In 3 wrists interpreted as being normal on plain films, despite clinical suspicion of a fracture, fractures were confirmed by computerized tomography. As a result of computerized tomography, injuries were assigned a higher Frykman value in 5 cases, and consideration of alternative patient management became necessary in 5 of the 22 patients. PMID- 1629559 TI - Open reduction and internal fixation for distal radius fractures. AB - From a series of 650 dorsally angulated fractures of the distal radius, 32 intra articular fractures were treated by open reduction and internal fixation. The 32 fractures were classified according to the Frykman criteria as type VII (5) or type VIII (27). On the basis of the location of intra-articular involvement, the fractures were further subdivided into Mayo type II (4), type III (18), and type IV (10). Results were analyzed by the methods of Gartland and Werley (functional) and Lidstrom (radiographic). After open reduction and internal fixation, 90% of the patients had satisfactory results on the basis of the subjective criteria of minimal deformity, absence of pain, and good strength. Objective assessment demonstrated that the patients had 80% of normal motion and 73% of normal grip strength at a minimum of 2 years after the operation. On the basis of radiographic and functional evaluation, results were good to excellent in 87%. When intra-articular step-off exceeded 2 mm or the radius was shortened more than 5 mm, the results were only fair and posttraumatic arthritis was evident. PMID- 1629560 TI - Multidirectional radiocarpal dislocation without fracture: a case report. AB - The first reported case of posttraumatic multidirectional instability of the radiocarpal joint is described with a review of the relevant literature. A 31 year-old man sustained a palmar radiocarpal dislocation that also dislocated dorsally with gentle provocation and showed ulnar translation and a dorsal intercalated segmental instability pattern after closed reduction. Treatment consisted of open reduction and internal fixation with 11 weeks of immobilization. Follow-up at 32 months showed excellent clinical and radiographic results. Multidirectional instabilities of the radiocarpal joint can occur with radiocarpal dislocation, and one must look for them when planning treatment. Anatomic realignment of the bones and joints is recommended to allow soft tissue healing and prevention of secondary ligamentous laxity. PMID- 1629561 TI - Transtriquetral perihamate ulnar axial dislocation and palmar lunate dislocation. AB - Transtriquetral perihamate ulnar axial dislocation associated with palmar lunate dislocation is a rare condition. We could find no other similar cases reported. The mechanism of injury was a combined anteroposterior crushing force that caused axial disruption of the carpus and the metacarpals and wrist hyperextension that caused the transtriquetral lunate dislocation. Our patient was treated with open reduction and internal fixation with good result. PMID- 1629562 TI - Three-dimensional reconstruction of the carpus and its vasculature: an anatomic study. AB - Three-dimensional reconstructions of the carpus have been assembled from tomographic data of anatomic specimens after vascular injection with resin polymer of a density similar to that of bone. We have been able to produce three dimensional reconstruction of the relationship between carpal bones and their vasculature. Fine tomographic slicing, on the order of 1 mm, has yielded sharp definition of bone structure, particularly of the entry points of nutrient vessels. The use of a very fluid synthetic resin has made possible the definition of vessels of fine caliber. A computerized program of three-dimensional reconstruction was used to obtain a series of views spaced at 10 to 20 degrees at predetermined right-angled axes. This has provided a precise matching of vessels with their corresponding points of bony penetration. This new method of imaging has enabled us to describe the entire vasculature of the bones of the carpus. The technique enjoys a number of advantages over conventional methods of study of carpal vasculature. In practice, the various known methods of arteriographic and digital angiographic examination do not have the same high definition and are unable to eliminate the effect of superimposition of views. In addition, the dissections are difficult and are likely to produce significant artifact. Corrosion techniques are elegant, but they are time-consuming, delicate procedures if selective isolation of bone and vasculature is required. PMID- 1629563 TI - Compressive forces. PMID- 1629564 TI - Effects of bile acids and bilirubin on bicarbonate secretion of isolated guinea pig antrum. AB - The effects of bile acids and bilirubin, which increase in blood in obstructive jaundice, on bicarbonate secretion were studied experimentally using isolated antral mucosa of the guinea pig. Antral mucosal preparations were mounted between Ussing chambers. Basal and bethanechol-stimulated secretion were measured by a pH stat device using 5 mM HCl. After 10(-4), 10(-3), and 5 x 10(-3) M taurocholic acid, 10(-4) and 10(-3) M cholic acid, and 1.2 x 10(-4) and 2.4 x 10(-4) M bilirubin conjugate were added to the serosal solution, basal and bethanechol stimulated secretion were also measured. Taurocholic acid, at any dose, did not affect basal secretion, but bethanechol-stimulated secretion was inhibited dose dependently. Cholic acid and bilirubin conjugate did not affect basal secretion, but bethanechol-stimulated secretion was significantly inhibited. Although the addition of bile acid or bilirubin into the serosal solution under experimental conditions is not the same as obstructive jaundice, these studies suggest that the inhibition of bicarbonate secretion in the gastric mucosa may have an important role in the formation of acute gastric mucosal lesions in obstructive jaundice. PMID- 1629565 TI - Determination of gastroduodenal alkaline responses using pH deflection in the rat. AB - We set up a new system for measuring the gastroduodenal HCO3- responses using pH deflection and the potential difference (PD) in the anesthetized rat. The stomach or the proximal duodenum was perfused at a flow rate of 0.7 ml/min with saline (pH 4.5), the pH of the perfusate and PD were continuously monitored, and HCO3- output was determined as acid-neutralizing capacity by back-titration of the perfusate to pH 4.5. In the case of the stomach, acid secretion was inhibited by omeprazole (60 mg/kg i.p.). Under these conditions, the pH, PD, and HCO3- output were 5.5 +/- 0.03, -3.8 +/- 0.4 mV, and 1.5 +/- 0.3 microEq/10 min in the duodenum and 5.4 +/- 0.04, -52.4 +/- 1.8 mV, and 1.2 +/- 0.3 microEq/10 min in the stomach, respectively. In addition, when various amounts of NaHCO3 were added into the system, a linear relationship was obtained between the area of pH deflection and the amount of added HCO3- (r = 0.999). Both pH and HCO3- output in these tissues were significantly increased by intravenous administration of prostaglandin E2, carbachol, and YM-14673 (a TRH analogue); the net HCO3- output in the duodenum was 8.7 +/- 1.3, 2.3 +/- 0.5, and 5.2 +/- 0.9 microEq, respectively. The values of net HCO3- output measured by back-titration coincided well with those obtained from the area of pH deflection caused by various agents. These results indicate that this system using pH deflection may be useful for quantitative determination of HCO3- response in the gastroduodenal mucosa. PMID- 1629566 TI - Helicobacter pylori has an ulcerogenic action in the ischemic stomach of rats. AB - Helicobacter pylori (H. pylori) is now accepted as an important cause of chronic active gastritis. There also seems to be an association between the colonization of H. pylori in the gastric mucosa and peptic ulceration. However, it has not demonstrated that the instillation of H. pylori into the stomach produces the ulcerative gastric lesions in animals or humans. We carried out an experiment to study whether or not H. pylori has an ulcerogenic action in the ischemic stomach of rats, using an ex vivo gastric chamber. The rat stomachs were exposed to 1 ml of H. pylori solution (200 IU of urease/ml) and 1 ml of urea (400 mg/dl) for 60 min after the creation of ischemia in the stomach (by withdrawal of 3 ml of blood). The exposure of the stomach to both H. pylori and urea resulted in severe hemorrhagic gastric mucosal lesions with a marked decrease in potential difference (PD) with a concomitant increase in ammonia concentration in rats with ischemia, whereas gastric lesions and a fall in PD were hardly observed in rats without ischemia. These results have demonstrated that H. pylori has an ulcerogenic action on the stomach subjected to mucosal ischemia. PMID- 1629567 TI - Protection of gastric mucosa against ethanol-induced injury by intragastric bolus administration of epidermal growth factor combined with hydroxypropylcellulose. AB - Orally administered epidermal growth factor (EGF) has been shown to protect the gastric mucosa against injury induced by noxious agents. However, EGF administered by intragastric bolus appears to have less effect on the gastric mucosa because of its rapid excretion from the gastric lumen. In this study, mouse EGF given to rats by gastric intubation was confirmed to remain in the stomach at significantly high concentrations when given in combination with hydroxypropylcellulose (HPC), an agent that retards drug release. The residual mouse EGF levels in the gastric luminal content and tissue 3 h after administration of 50 micrograms/kg of EGF dissolved in 1 ml of 2% HPC were 30 and 60 times higher, respectively, than those obtained after EGF alone. Pretreatment with intragastric bolus administration of EGF and HPC at the same dose for 3 h attenuated significantly the development of gastric lesions induced by absolute ethanol compared to that with HPC alone, EGF alone, or saline (mean values of ulcer index: EGF + HPC, 14.3; HPC, 52.8; EGF, 50.7; and saline, 63.2 mm). There were no significant differences between the ulcer index in the HPC, EGF, and saline groups. The present study indicates that exogenous EGF given as an intragastric bolus protects the gastric mucosa against injury when combined with HPC, which can bind to EGF and prevent its rapid excretion from the gastric lumen. PMID- 1629568 TI - Changes in superoxide dismutase activity in the gastric mucosa of peptic ulcer patients. AB - A highly sensitive chemiluminescence method for determining superoxide dismutase (SOD) activities in human gastric mucosa obtained by endoscopic biopsy is described. As the chemiluminescence probe, we used Cypridina luciferin analogue (CLA), a very sensitive and specific probe to detect superoxide generated from hypoxanthine-xanthine oxidase system. SOD activity in the gastric mucosa was assayed by the inhibition of CLA-dependent chemiluminescence in highly diluted tissue homogenates. SOD activity was distributed throughout the gastric mucosa. The marginal mucosa of peptic ulcers showed significantly lower SOD activity when the ulcer was in the active stage, and during the healing stage showed high activity when compared to the endoscopically normal adjacent mucosa of the same patients. The preliminary data suggest that enzymatic SOD in the gastric mucosa may play an important role in the pathogenic and healing processes of human peptic ulcers. PMID- 1629569 TI - Correlations between the acute chemical and surgical vagotomy-induced gastric mucosal biochemistry in rats. AB - The aims of the present investigation were to compare the acute chemical (atropine given in a dose of 1.0 mg/kg s.c.) and bilateral surgical vagotomy induced biochemical changes in the rat gastric mucosa. The biochemical measurements were carried out at 1.5 h after administration of atropine and surgical vagotomy. The adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and lactate were measured enzymatically, and cyclic adenosine monophosphate (cAMP) was determined by RIA, from the total homogenate of gastric mucosa. The ratio of ATP/ADP, values of the adenylate pool (ATP + ADP + AMP), and energy charge [(ATP + 0.5 ADP)/(ATP + ADP + AMP)] were calculated. It was found that (a) no significant changes were obtained in the gastric mucosal levels of ATP, ADP, AMP, adenylate pool, cAMP, lactate, and ratio of ATP/ADP, but were with energy charge, which decreased in rats with acute surgical vagotomy; (b) the tissue levels of ATP, ADP, ratio of ATP/ADP, AMP, and adenylate pool were decreased, while the energy charge and cAMP increased in the atropine-treated group; and (c) significant differences were obtained between the chemical and surgical vagotomy-induced changes in the tissue levels of ATP, ADP, ratio of ATP/ADP, AMP, adenylate pool, energy charge, and cAMP. It is concluded that the chemical and surgical vagotomy-induced biochemical changes in the gastric mucosa differed significantly at 1.5 h after administration of atropine or surgical vagotomy, but no elevation was obtained in the gastric mucosal level of lactate; and chemical vagotomy regulates the membrane-bound ATP-dependent energy systems, but this regulation does not occur after surgical vagotomy. PMID- 1629570 TI - Mechanisms of vagal nerve in gastric mucosal defense: unchanged gastric emptying and increased vascular permeability. AB - Gastric cytoprotection in response to different agents (prostaglandins, carotenoids, etc.) failed to occur after surgical vagotomy. Decreased gastric emptying and the increased vascular permeability were tested in ethanol-treated rats without and with bilateral surgical vagotomy. The experiments were carried out on Sprague-Dawley rats. The animals were fasted for 24 h before experiments. Bilateral surgical vagotomy or only laparatomy were carried out at 30 min before administration of ethanol (96%, 1 ml). The animals were killed at 0, 1, 5, 15, and 60 min after ethanol administration, when the number and severity of gastric mucosal lesions were noted. In another series of experiments, the animal received Evans blue (1 mg/100 g) i.v. 15 min before killing. The gastric contents were collected and the glandular mucosa was scraped. Evans blue was extracted in chloroform, and its concentration was spectrophotometrically measured. It has been found that (a) both number of lesions and severity of ethanol-induced gastric mucosal damage were larger at each time period in surgically vagotomized rats than in rats with intact vagal nerves; (b) the increased vascular permeability was significantly higher in gastric mucosa at an early period in surgically vagotomized rats compared to rats with intact vagal nerve; (c) the increased vascular events preceded the development of macroscopic appearance of gastric mucosa damage in both groups of animals; and (d) the time-related responses were the same in both groups of animals. It is concluded that increased vascular permeability, but not gastric emptying, probably has some role in the failure of the development of gastric cytoprotection in surgically vagotomized rats. PMID- 1629571 TI - Stress-induced gastric mucosal lesion and platelet aggregation in rats. AB - The effect of cold-restraint stress on platelet function in vitro was studied in the rat model. Platelet function was assessed by platelet aggregation in response to adenosine diphosphate (ADP) and thrombin. ADP-induced platelet aggregation was reduced in platelet-rich plasma after 2 h of cold-restraint stress. Thrombin induced platelet aggregation was reduced with time during cold-restraint stress with a parallel increase in the lesion index. Although pretreatment of animals with atropine prevented the development of gastric mucosal lesions, platelet dysfunction was not reversed by this treatment. These results suggest that cold restraint stress may impair platelet function, probably due to platelet activation in vivo, and that the abnormalities in platelet function may be associated with the development of gastric mucosal lesions. PMID- 1629572 TI - Gastric antisecretory and antiulcer actions of interleukin-1. Evidence for the presence of an "immune-brain-gut" axis. AB - Increasing evidence suggests that interleukin-1 (IL-1), a cytokine mainly produced by activated monocytes/macrophages, has various biological actions in addition to its immunological activities. In the present study, we examined the effect of IL-1 on gastric secretion and gastric ulcer formation in rats. Gastric secretion was assessed in conscious pylorus-ligated rats weighing approximately 200 g. The peripheral injection of IL-1 resulted in a dose-related inhibition of gastric acid output. The central injection of IL-1 similarly reduced gastric acid secretion at 100 times smaller doses than peripherally injected IL-1, suggesting that this gastric antisecretory action of IL-1 is mediated by the central nervous system. In addition, it was found that this inhibitory effect of IL-1, either peripherally or centrally administered, was still evident at 8 h after injection, indicating the long-lasting property of this IL-1 action. On the basis of these antisecretory actions of IL-1, we determined whether or not pretreatment with IL 1 would prevent experimentally induced gastric ulcer formation. As expected, the central administration of IL-1 dose-dependently suppressed the development of gastric mucosal lesions induced by water-immersion restraint stress, a well established ulcerogenic procedure. These results clearly demonstrated that IL-1 has potent antisecretory and antiulcer effects that are mediated by the central nervous system. Moreover, these findings suggest that there may exist an "immune brain-gut" axis, which is involved in the regulation of gastric secretion and mucosal homeostasis, especially under certain pathophysiological conditions that activate the immune system to release various cytokines including IL-1. PMID- 1629573 TI - Severe gastric mucosal changes following vagotomy with duodenogastric reflux. AB - We conducted an experimental study of the morphological changes in gastric mucosa following vagotomy, in particular of the chronic effects of duodenogastric reflux. Male Wistar rats were divided into four groups: sham operation, duodenogastric reflux (DGR), truncal vagotomy with duodenogastric reflux (TV + DGR), and truncal vagotomy with bypass (TV + bypass). The last operation was performed to observe the effects of vagotomy without reflux. The duodenogastric reflux procedure was established by cutting the duodenum just distal to the orifice of bile and pancreatic ducts following gastrojejunostomy. After 12 and 30 weeks, animals were killed for morphological studies of gastric mucosa. The TV + DGR group showed formation of multiple elevated lesions macroscopically, and microscopically showed marked atrophy of gastric glands and proliferation of cystically dilated adenomatous lesions, which were regarded as precancerous or paracancerous lesions. The DGR group showed chronic gastric ulcer and hyperplasia of the gastric glands. However, the TV + bypass group showed no remarkable changes in the gastric mucosa. These results indicate that chronic effects of duodenogastric reflux following vagotomy induce severe inflammatory changes as well as structural alteration of the gastric mucosa. Therefore, a regular follow up observation is necessary after vagotomy when combined with a drainage procedure because the latter could promote duodenogastric reflux and produces pathological changes to the stomach. PMID- 1629575 TI - Epithelial renewal in premalignant conditions of the gastrointestinal tract: a review. AB - The constant rapid renewal of the epithelium of the gastrointestinal (GI) tract is important in the development of neoplasms that are derived from the epithelium as well as in maintaining the functional integrity of the mucosa. An abnormality of epithelial proliferation, characterized by an increase in numbers of proliferating cells and expansion of the proliferative zone, is common to all human premalignant conditions of the GI tract that have been studied, including Barrett's epithelium, chronic gastritis, ulcerative colitis, and colonic polyps, and is a consistent observation after the use of experimental carcinogens, such as N-methyl-N-amylnitrosamine and N-methyl-N'-nitro-N-nitrosoguanidine. These abnormalities also have been observed in some relatives of patients with colonic polyps or cancers who themselves do not have any demonstrable colonic lesion. Calcium, vitamins A, C, and E, and other agents have been shown to reverse the abnormalities in proliferation in some experimental and clinical conditions, which raises the question of whether some of these agents can be used to reduce the risk of development of cancer in patients with known premalignant conditions of the GI tract. PMID- 1629574 TI - Gastric epithelial cell proliferation after injury. AB - The mucosa of the gastrointestinal tract, including the stomach, undergoes constant renewal. The gastric mucosa is able to regenerate after injury, and this regeneration is associated with increases in epithelial cell proliferation. Gastric epithelial regeneration has been suggested to be impaired with aging. Using a hyperosmolar injury model, we found that gastric epithelial proliferation was markedly lower in aged rats. To elucidate further the regulation of gastric epithelial proliferation after injury, we studied the induction of ornithine decarboxylase and tyrosine kinase. Ornithine decarboxylase is the first and often rate-limiting enzyme in polyamine biosynthesis and tyrosine kinase catalyzes phosphorylation of protein tyrosine residues, and both enzymes have been implicated as important in cell proliferation. We found that hyperosmolar injury induction of ornithine decarboxylase and tyrosine kinase was markedly lower in aged rats. Furthermore, inhibition of ornithine decarboxylase or of tyrosine kinase greatly suppressed gastric epithelial proliferation. Our results confirm that ornithine decarboxylase and tyrosine kinase are important in gastric epithelial proliferation. Further studies of these two enzyme pathways may help elucidate the regulation of gastric epithelial growth and regeneration, particularly the potential alterations with aging. PMID- 1629576 TI - Prostaglandin but not cimetidine reduces spontaneous degeneration of isolated gastric gland cells. AB - We studied the effect of either placebo, 16,16-dimethyl-prostaglandin E2 (16,16 dimethyl-PGE2), or cimetidine on spontaneous degeneration of isolated rat gastric glands maintained in vitro in a basic oxygenated medium for 24 h. We assessed the viability of gland cells with fast green exclusion, measured release of lactate dehydrogenase (LDH) into the medium, and assessed the cell ultrastructure using a scanning electron microscope. Gastric glands incubated in medium for 6, 12, and 24 h underwent spontaneous degeneration reflected by a decrease in cell viability, increase in LDH release into the medium, and ultrastructural cell damage. 16,16-Dimethyl-PGE2 either at 0.1, 1, or 10 micrograms/ml significantly reduced the decrease in cell viability, increasing cell survival; reduced LDH release into the medium; and ultrastructural damage. Incubation with cimetidine at 1 or 10 micrograms/ml did not affect cell viability at 6, 12, or 24 h, whereas 100 micrograms/ml reduced cell viability (vs. placebo) at 12 and 24 h. LDH release and ultrastructural damage were not affected (not reduced) by cimetidine. Our study indicates that 16,16-dimethyl-PGE2, but not cimetidine, directly protects isolated gastric gland cells against degeneration in vitro, under conditions independent of systemic, neural, and hormonal factors. PMID- 1629577 TI - Effect of sofalcone on localization of 15-hydroxyprostaglandin dehydrogenase, an enzyme that metabolizes prostaglandin E2, in rat gastric mucosa: an immunohistochemical study. AB - We identified the cells containing 15-hydroxyprostaglandin dehydrogenase (15 HPGD) in rat gastric mucosa and examined the effects of sofalcone on the localization of the enzyme by use of an immunohistochemical technique. Also, we investigated the effects of sofalcone on the localization of prostaglandin E2 (PGE2). Specific stainings for 15-HPGD and PGE2 were similarly observed in a granular pattern mainly in the cytoplasm of parietal and surface epithelial cells. The number of the stained cells for 15-HPGD, especially surface epithelial cells, decreased when rats were given sofalcone, with a concomitant increase in PGE2 staining. These results suggest that parietal and surface epithelial cells are responsible for the degeneration of PGE2 in the rat gastric mucosa, and that sofalcone increased the PGE2 level in the mucosa through inactivation of 15-HPGD in these cells, especially surface epithelial cells. PMID- 1629578 TI - Cytoprotection by 16,16-dimethylprostaglandin E2. Role of gastric juice and mucus gel layer. AB - A mechanism of cytoprotection by 16,16-dimethylprostaglandin E2 (16,16-dimethyl PGE2) was investigated in rats with respect to possible roles of the gastric juice and the mucus gel layer. 16,16-Dimethyl-PGE2 significantly increased the volume of gastric juice and mucus thickness. In a gastric juice-emptied stomach, 16,16-dimethyl-PGE2 protected the gastric mucosa against 30% ethanol, but not against 40% ethanol. Moreover, this agent did not show any cytoprotective action even against 30% ethanol when both gastric juice and mucus gel were removed. In this situation there was no histological change in the depth of injury, whether 16,16-dimethyl-PGE2 was given as pretreatment or not. These results suggest that there are two mechanisms that may play major roles in the cytoprotection of the gastric mucosa by 16,16-dimethyl-PGE2: (a) dilution of necrotizing agents by increased gastric juice and (b) thickening of the mucus gel layer. PMID- 1629579 TI - Early ultrastructural changes of surface epithelial cells isolated from rat gastric mucosa after exposure to ethanol with or without 16,16 dimethylprostaglandin E2. AB - Early ultrastructural changes of surface epithelial cells isolated from rat gastric mucosa caused by 15% ethanol were studied. The effect of 16,16 dimethylprostaglandin E2 (16,16-dimethyl-PGE2) on these changes was also examined. Findings by transmission electron microscopy showed ballooning and decreased density of mitochondria in addition to loss of microvilli and partial disruption of the surface cell membrane in cells exposed to 15% ethanol, although the nucleus looked normal. These ultrastructures were well preserved even after exposure to 15% ethanol when the cells were treated with 10(-6) M 16,16-dimethyl PGE2 beforehand. These results may indicate that the surface cell membrane and mitochondria are the major targets for early injury by ethanol and protection by 16,16-dimethyl-PGE2 in surface epithelial cells. The mechanism by which 16,16 dimethyl-PGE2 prevents the damage is not known. PMID- 1629580 TI - Role of leukotrienes in gastric mucosal injury induced by ischemia-reperfusion in rats. AB - This study was designed to clarify the role of leukotrienes (LTs) in gastric injury induced by ischemia-reperfusion in rats. Gastric lesions were produced by clamping of the celiac artery and by reoxygenation following clamping. Administration of AA-861, a lipoxygenase inhibitor, significantly inhibited the increase in the total area of the gastric erosions and the increase in thiobarbituric acid-reactive substances in the gastric mucosa. Administration of YM-638, a peptide LT antagonist, showed protective effects similar to AA-861. These results suggest that the protective effects of AA-861 and YM-638 against ischemia-reperfusion-induced gastric injury were due to their antioxidative action. PMID- 1629581 TI - Histopathological development of gastric tumors induced by N-methyl-N'-nitro-N nitrosoguanidine in rats. AB - The development of carcinoma was examined in male Wistar rats (n = 120) exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking water (83 micrograms/ml) for 16 weeks. After MNNG administration, rats were investigated by endoscopic observation, visualization of microvascular structure, and estimation of lectin binding sites. Changes of bile reflux to the stomach was observed endoscopically at 24 weeks as well as the development of gastric mucosal erosions. Protruding and expansive ulcerating carcinomas developed at 36 weeks and had a microvascular pattern similar to that of human adenocarcinoma. Estimation of lectin binding site and pattern was useful to evaluate the malignant potential of cell proliferation. We postulate that endoscopic observation is valuable in investigating the development of gastric carcinoma, and microvascular structure and lectin binding pattern may be useful to demonstrate the mechanism of growth of gastric carcinoma. PMID- 1629582 TI - Effects of anti-acid secretory agents on various types of gastric mucus. AB - Total, acidic, and sulfated mucus contents in the gastric mucosa were evaluated after administration to rats of ranitidine and pirenzepine, antagonists of gastric parietal cell receptors; omeprazole, a proton-pump/inhibitor; and misoprostol, a prostaglandin E1 preparation. Total gastric mucus content was significantly decreased by ranitidine, but contents of acidic mucus and sulfated mucus showed a slight increase. Total mucus and acidic mucus contents were slightly increased after administration of pirenzepine, whereas the sulfated mucus content was significantly increased. The total gastric mucus content was significantly decreased after administration of omeprazole, but acidic mucus increased slightly and sulfated mucus increased significantly. All mucus contents were unchanged after administration of anti-acid secretory dose of midoptodyol. After administration of either ranitidine or omeprazole, the neutral mucus content decreased, but the total acid and sulfated mucus contents were not decreased. Changes in various mucus contents following inhibition of acid secretion are different for different drugs, and it was suggested that production of neutral mucus and secretion of acid mucus were reduced by strong inhibition of acid secretion. PMID- 1629583 TI - Demonstration of bicarbonate secretion in rat duodenal brush border membrane vesicles. AB - This study was designed to characterize the mechanisms available for bicarbonate transport across the apical membrane using rat duodenal brush border membrane vesicles (BBMVs), including the morphological findings. BBMVs were purified using a double Mg2+ precipitation technique. Electron microscopy of the final pellet showed only membrane material without contaminating organelles of cytoskeletal aggregates. BBMVs were enriched 15.1 +/- 3.2-fold in A-lp and 12.5 +/- 2.4-fold in LAP. The time course of 36Cl uptake into BBMVs demonstrated a good response curve and equilibrated to the intravesicular space over 120 min. In this present study, these BBMVs were purified and showed a stabilized structure. Therefore, these results suggest that this model was useful for studying HCO3- secretion and ulcer etiology. PMID- 1629584 TI - Gastric emptying in the acutely inebriated patient. AB - Fifty inebriated emergency department (ED) patients underwent evacuation of gastric contents via a nasogastric tube, in order to determine if a significant amount of ingested ethanol can be removed prior to absorption. Such a result could potentially reduce additional intoxicating effect. The gastric contents were assayed for total ethanol concentration, and a potential (postabsorption) additive blood alcohol level (PABAL) was projected and compared to the actual BAL on arrival. The type of beverage ingested and the time since last drink were recorded. BAL ranged from 108 to 637 mg/dL (mean +/- SD, 290 +/- 104.7). Gastric aspirate volume ranged from 50 to 700 mL (190 +/- 134), and contained alcohol in a range of 87 to 2271 mg/dL (475 +/- 479). Based on the distribution volume for alcohol calculated according to the patient's weight, this corresponded to a PABAL of 3 to 167 mg/dL (mean, 24.3 +/- 29.3). There was no significant correlation between the volume or concentration of gastric aspirate and the patient's stated drinking history. The authors conclude that a significant amount of ingested alcohol may occasionally be removed from absorption by the routine evacuation of gastric contents in intoxicated patients. These patients cannot be identified upon presentation, however, and these data cannot support routine use of gastric emptying in the detoxification of inebriated patients. PMID- 1629585 TI - Concurrence of multiple sclerosis and Hodgkin's disease. AB - Although multiple sclerosis and Hodgkin's disease are reported to have similar epidemiologic features, this is only the first case report in which there was concurrence of these diseases. Fourteen years after successful treatment of Hodgkin's disease, this 31-year-old white male developed multiple sclerosis. The diagnosis of multiple sclerosis was made on the basis of clinical and paraclinical findings that were characteristic of multiple sclerosis. In addition, specific tests were performed to rule out a variety of infectious, metabolic, and neoplastic diseases that simulate multiple sclerosis. PMID- 1629586 TI - Exsanguinating hemorrhage from a caput medusae: cutaneous variceal bleeding. AB - We report the case of a 45-year-old female who presented to the emergency department with massive umbilical hemorrhage from a cutaneous varix. The patient had a long-standing history of alcohol-related liver disease and ascites. Her clinical course was complicated by coagulopathy and hemorrhagic shock, and she ultimately expired. Ectopic or nongastroesophageal bleeding constitutes a significant site of variceal hemorrhage. In this report we review the literature and explore methods of treatment. PMID- 1629587 TI - Tension gastrothorax complicating acute traumatic diaphragmatic rupture. AB - Herniation of abdominal viscera into the thorax following traumatic diaphragmatic hernia can simulate acute tension pneumothorax. A case is presented of a blunt trauma victim with apparent acute diaphragmatic rupture, tension hemothorax, or tension hemopneumothorax. Nasogastric tube insertion demonstrated tension gastrothorax, but was followed by acute clinical decompensation. Percutaneous needle thoracostomy decompressed the stomach without causing spillage of gastric contents. Autopsy experimentation was performed to demonstrate that needle decompression of the distended stomach is well tolerated. Tension gastrothorax is a rare, life-threatening complication of traumatic diaphragmatic hernia. Although nasogastric tube placement should be attempted first, it may exacerbate the condition. Percutaneous needle decompression of the stomach through the chest wall can stabilize the situation and is safer and more rapid than chest tube placement, which might be either ineffective or dangerous. Paralyzing the patient with acute diaphragmatic rupture before tracheal and gastric intubation might prevent progression to tension gastrothorax. PMID- 1629588 TI - Complete recovery following an unusual cardiac stab wound. AB - A 17-year-old female was stabbed in the chest and found by paramedics in extremis. She arrived at the receiving hospital with spontaneous respirations and an improved blood pressure. Upon thoracotomy in the operating room, lacerations through the main pulmonary artery and the left atrium were found. The combined efforts of a sophisticated EMS system providing rapid in-field stabilization and transport, a ready in-house trauma team able to quickly assess and provide definitive care, and a prepared operating room team, including cardiopulmonary bypass capability, resulted in a complete and uncomplicated recovery from this rare and lethal injury. PMID- 1629589 TI - Azygos vein laceration following a vertical deceleration injury. AB - A 41-year-old man presented with respiratory distress and hypotension after a 30 foot fall from a tree. Despite fluid resuscitation, the patient expired in the operating room. Autopsy revealed an azygos vein laceration at the junction of the superior vena cava as the cause of death. Azygos vein and superior vena caval lacerations are rare following blunt chest trauma, including vertical deceleration injury. Early suspicion of vascular injuries with aggressive fluid resuscitation and surgical intervention remain the only hope for survival from this highly lethal injury. PMID- 1629590 TI - Human parvovirus B-19: not just a pediatric problem. AB - Parvoviruses have long been associated with disabling and even fatal illnesses in animals. The discovery of the human parvovirus B-19 in 1975 (1) and subsequent studies of its effects in humans identified this virus as the causative agent of erythema infectiosum ("fifth disease") in children. (2). Erythema infectiosum (EI) is a common, self-limited infectious disorder in children, easily recognized by the classic "slapped cheek" facial erythema and fine reticular rash. Only in the 1980s have further investigations linked HPV B-19 infection with more significant clinical syndromes, among which is an adult polyarthropathy. This presentation in adults is more common than is currently understood and is easily confused with other symmetric polyarthropathies. Recognition and conservative treatment of this disorder are important for the emergency physician, to whom these patients may present. PMID- 1629591 TI - Neurogenic pulmonary edema: case reports and review. AB - Neurogenic pulmonary edema (NPE) is a relatively common though often subclinical complication of a variety of central nervous system insults (trauma, hemorrhage, seizures, etc.) in children and adults. The syndrome probably results from massive centrally mediated sympathetic discharge and generalized vasoconstriction, and often presents in the emergency department (ED). The symptoms are likely to be mistaken for aspiration pneumonia. Treatment consists of ventilatory support, including positive end-expiratory pressure, and aggressive measures to reduce intracranial pressure. We present four cases of NPE and review its recognition and emergent management. PMID- 1629592 TI - Minoxidil overdose with ECG changes: case report and review. AB - A 20-year-old female ingested an unknown quantity of minoxidil tablets as a suicide gesture. She presented to the emergency department about 90 minutes later with tachycardia, diffuse T wave inversion, and S-T segment depression on the ECG, labile hypotension, and a substantially elevated total serum minoxidil concentration of 3140 ng/mL. She responded to supportive therapy with intravenous fluids, and was discharged 32 hours later with stable blood pressure and mild residual tachycardia. The clinical toxicology, treatment, and previous case reports of minoxidil overdose are reviewed. PMID- 1629593 TI - Cocaine adsorption to activated charcoal in vitro. AB - Although activated charcoal (AC) is commonly used after ingestions of cocaine, the ability of AC to bind with this drug is unknown. We studied binding of cocaine to AC in vitro. Cocaine adsorption to charcoal for AC:drug ratios of 1:1, 2.5:1, and 5:1 at pH 1.2 was 40%, 92%, and 99%, respectively; at pH 8.0, it was 78%, 98%, and 99%, respectively. All means were significantly different (P less than 0.05) versus the control (no AC) at each pH. At the AC:drug ratio of 1:1, there was also significantly greater adsorption of cocaine at pH 8.0 than at pH 1.2. This study shows that AC strongly adsorbs cocaine under both acidic and alkaline conditions. PMID- 1629594 TI - Mechanical performance of disposable surgical needle holders. AB - The mechanical performance of disposable Webster surgical needle holders supplied by three different surgical instrument companies was determined by recording the forces (clamping moment) applied by the different needle holder jaws to curved surgical needles. This investigation demonstrated that there was a large variability in the mechanical performance of the disposable needle holders supplied by each surgical instrument company. In addition, the mechanical performance of the disposable needle holder of each surgical instrument company was distinctly different. PMID- 1629595 TI - Effective hand degerming in the presence of blood. AB - This study evaluated the effect of blood on the antimicrobial activity of several agents used for handwashing. Seventy-one healthy adult volunteers used 1 of 6 products (70% isopropyl alcohol [IPA]; liquid hand rinse containing 70% ethyl alcohol and 0.5% chlorhexidine gluconate [EA]; detergent containing 7.5% povidone iodine [PI]; detergent containing 4% chlorhexidine gluconate [CHG]; a nonantimicrobial soap; and a control group that used no product) in two tests: with and without 1.2 mL of dried sterile sheeps' blood on the hands. In the presence of blood, the two alcohol products (IPA and EA) resulted in significantly greater reductions in numbers of colony-forming units than other products (P less than 0.001). When no blood was present, IPA was associated with significantly greater reductions, whereas soap and control groups had significantly lower reductions (P = 0.008). We conclude that hands are effectively degermed with a variety of products in the presence of blood, and that alcohols give greater initial reductions in colonizing flora. This is of particular relevance in emergency situations during which contamination with blood is likely and handwashing facilities are inaccessible. PMID- 1629596 TI - Flatology. AB - Advances in flatology are often close-lipped but of note. Cultural constraints and scatologic implications at times impede meaningful research. Historical and contemporary perspectives on flatus range from the biblical and theatrical, to paleontologic and environmental concerns, to the omninauseant legal and psychiatric sequelae. The current state of flatal physiology, pathophysiology, and diagnosis of aberrancy are reviewed. Flatoanalysis, air-flow studies, and flatulograms are discussed, as well as various remedies. PMID- 1629597 TI - Alexander Fleming: the spectrum of penicillin. AB - The discovery of penicillin was directly linked to the inhibition by that agent of the growth of colonies of staphylococcus. However, subsequent resistance by this organism to penicillin as well as to a number of other agents has marked the history of staphylococcus in the antibiotic era. One of the most important mechanisms of this resistance has been the production of penicillinase, an enzyme that inactivates penicillin and related antibiotics. Penicillinase is currently termed beta-lactamase, and it is now recognized that there are several types of beta-lactamases produced by various organisms. The ability of staphylococci to produce this enzyme has been countered by the development of penicillinase resistant agents and the addition of beta-lactamase inhibitors to antibiotics. PMID- 1629598 TI - ED overcrowding in New York City. PMID- 1629599 TI - Annual reports. PMID- 1629600 TI - Mid-shift musings of a practicing emergency physician. PMID- 1629601 TI - Objectives to direct the training of emergency medicine residents on off-service rotations: pulmonary. AB - This article outlines the objectives for a resident rotation in pulmonary diseases. It is part of a continuing series on the goals and objectives to direct Emergency Medicine resident training on off-service rotations. Pulmonary disease accounts for a high percentage of presenting complaints and potentially life threatening disease in the emergency department. Because of the frequency of respiratory disease in Emergency Medicine, many Emergency Medicine residencies offer individual off-service rotations in Pulmonary Medicine. The objectives of this article are viewed as a one-month component of an Internal Medicine Rotation in the first year of training. These objectives are designed to help focus the resident's reading and study during a pulmonary off-service rotation. PMID- 1629603 TI - The natural anti-alpha-galactosyl IgG in seminal fluid. A simple means to determine damage to the blood-genital tract barrier in infertile males. AB - A simple method for detecting damage to the blood genital tract barrier (BGTB) is presented. The method is based on the ubiquitous presence of the natural anti alpha-galactosyl (anti-Gal) IgG antibodies in high titers in the serum of every normal individual, and the interaction between this antibody and alpha-galactosyl residues on rabbit red blood cells (RabRBC). The binding of the anti-Gal antibodies to RabRBC could be demonstrated by the rosetting antiglobulin test. The seminal fluid (SF), normally compartmentalized from the blood, is devoid of anti-Gal reactivity. The SF of a large proportion of infertile males contained significant anti-Gal reactivity, implying transudation of serum IgG molecules probably due to damage in the selective permeability of the BGTB. The diagnostic potential of this assay is discussed. PMID- 1629602 TI - Electroporation of CTL clones: a useful method to investigate signalling pathways leading to the expression of effector functions. AB - Signal transduction mechanisms leading to effector functions in mouse cytolytic T lymphocyte (CTL) clones were studied following the introduction of exogenous molecules by electroporation. Conditions were defined in which the application of an electric pulse permeabilized the CTL without affecting functions such as antigen-dependent or antibody-mediated cytotoxicity. When a non-permeant Ca2+ chelator such as EGTA was added in the external medium during the electric pulse, it inhibited subsequent target cell cytolysis carried out in the presence of external Ca2+, thereby indicating the efficiency of EGTA uptake. Results obtained in this system, using a 13 amino-acid protein kinase C (PKC) pseudo-substrate peptide, indicated that it selectively inhibited cytolysis, whereas a substrate peptide with one amino-acid substitution was not inhibitory. This suggests that the technique could be used to study the signal transduction mechanisms of CTL clones which lead to the expression of effector functions. PMID- 1629604 TI - Measurement of PAF in blood by radioimmunoassay. Examination of interfering factors and problems involved in accurate quantification. AB - A recently developed radioimmunoassay for PAF was applied to blood extracts with the aims of defining and overcoming problems that lead to erroneous results and establishing optimum conditions for the accurate determination of PAF levels. The high lipid content of blood was found to interfere with the assay, and it appeared that phosphatidylcholine and/or sphingomyelin might be among the lipids responsible. Interference was eliminated by either dilution or preparative TLC of blood extract prior to RIA although dilution is unlikely to be generally useful due to the low amounts of PAF normally present in human blood. Lipid extraction of whole blood followed by preparative TLC proved to be necessary in the preparation of samples prior to performance of the RIA. The problems encountered in the measurement of PAF levels in blood by RIA highlight the importance of determining the correct method of sample preparation for any tissue/fluid prior to its inclusion in the assay. PMID- 1629605 TI - Monoclonal antibody mediated targeting of enzymes. A comparative study using the mouse spleen as a model system. AB - The aim of this study was to target enzymes specifically to cells in the murine spleen. Monomeric and polymeric conjugates of the enzymes horseradish peroxidase or alkaline phosphatase and monoclonal antibodies against cell surface determinants were prepared. Highly specific in vivo targeting of enzymes to macrophages was obtained only when monomeric MAb-enzyme conjugates were used. PMID- 1629606 TI - Analyses of affinity distributions within polyclonal populations of antigen specific antibodies. Evaluation of their accuracy in population detection using monoclonal antibodies. AB - The potential of an ELISA based detection of affinity distributions within polyclonal populations of antigen-specific serum antibodies was assessed by analyzing defined probes composed of monoclonal antibodies (MAb). In a competitive binding ELISA in which the concentration of antigen in the liquid phase and the solid phase was varied, we analyzed mixtures containing defined percentage compositions of MAb exhibiting apparent affinity constants (aK) between 3 x 10(6) and 2 x 10(9) M-1 for Pseudomonas aeruginosa exotoxin A. Our results indicate that the detectability of antibody populations depends on the antigen concentrations in the solid phase and on the affinity distribution of the probe to be analyzed. In wells coated with high antigen concentrations, antibody titers reflected antibody concentrations, whereas at low antigen concentrations antibody titers primarily reflect antibody affinities. Independent of their affinities, subpopulations less than 10% could not be detected. Low affinity antibodies were preferentially underestimated. The degree of distortion depended on the composition of the probe to be analyzed. In general, the higher the absolute and the relative affinity of a population, the stronger was its capacity to interfere with the detection of other populations. As a consequence, the heterogeneity of affinity distributions in polyclonal samples may be substantially underestimated. The experiments reported provide guidelines for an optimal design and an adequate interpretation of ELISA based qualitative analyses of polyclonal antibody samples. PMID- 1629607 TI - Production and characterisation of monoclonal antibodies against native and disassembled human catalase. AB - Catalase isolated from human erythrocytes was used to immunise mice, in order to generate hybridomas producing specific monoclonal antibodies to the enzyme. Hybridomas secreting anti-(catalase) antibodies were identified by a modified enzyme-linked immunosorbent assay (ELISA) using either monomer/dimer catalase or native, tetrameric enzyme. Three stable hybridoma clones were selected and the characteristics of the antibodies produced were investigated by ELISA, immunofluorescence, immunoprecipitation and immunoblotting experiments. One monoclonal antibody (17E10) was shown to interact with both native tetramer catalase and--to a lesser extent--with monomer/dimer catalase. Two monoclonal antibodies (10B12H9, 13A10) were found to react only with completely denatured catalase or with monomer/dimer catalase but not with native catalase. PMID- 1629608 TI - The development of a quantitative assay for the detection of anti-Ro/SS-A and anti-LA/SS-B autoantibodies using purified recombinant proteins. AB - A characteristic of patients with autoimmune diseases such as Sjogren's syndrome and systemic lupus erythematosus is the presence of anti-Ro/SS-A and anti-La/SS-B autoantibodies in their circulation. In order to investigate specific autoantibody levels in the sera of these patients quantitative assays for the detection of both anti-Ro/SS-A and anti-La/SS-B reactivity were developed. Ro/SS A (60 kDa) and La-SS-B (50 kDa) cDNAs were cloned and expressed in E. coli as non fusion proteins. These were purified to homogeneity using two different purification protocols. With these recombinant antigens, specific enzyme-linked immunosorbent assays (ELISAs) were developed. 40 sera positive for anti-Ro/SS-A autoantibodies in counterimmunoelectrophoresis (CIE) were tested in both the Ro/SS-A and La/SS-B ELISA. Activity values reproducibly ranged from 1536 to 120,000 U in the Ro/SS-A ELISA and from 763 to 2,500,000 U in the La/SS-B ELISA. The suitability of these ELISAs as screening assays was further investigated by testing 200 sera sent to our laboratory for routine detection of autoantibodies to extractable nuclear antigen (ENA: anti-Sm, anti-RNP, anti-Ro/SS-A and anti La/SS-B). Both ELISAs showed a high sensitivity and specificity (Ro/SS-A ELISA 85% and 94%, La/SS-B ELISA 100% and 98% respectively), when compared to the standard assays, the RNA-precipitation assay and the HeLa immunoblotting test. From these data we conclude that a quantitative analysis of both anti-Ro/SS-A and anti-La/SS-B autoantibodies is now possible using purified recombinant non-fusion proteins. For screening purposes the La/SS-B ELISA showed a great improvement in sensitivity for the detection of anti-La/SS-B activity in comparison to the La/SS B CIE, while the Ro/SS-A ELISA almost equalled the performance of the Ro/SS-A CIE. PMID- 1629609 TI - In situ immunocytochemical detection of cells containing antibodies specific for Eimeria tenella antigens. AB - A three-step immunocytochemical method for the in situ detection of antibodies specific for Eimeria tenella has been developed. The method is based on the binding of E. tenella antigens to antibodies in cryostat sections of chicken tissues and the recognition of these antigens by rabbit antiserum specific for E. tenella or mouse monoclonal antibodies specific for E. tenella. The rabbit antiserum and mouse monoclonal antibodies were revealed by the immunoperoxidase technique. Suspensions of sonicated sporulated oocysts, incubated with or without various concentrations of the non-ionic detergents Triton X-100 (TX-100) or Nonidet P-40 (NP-40), were used as antigen. Cells containing antibodies specific for E. tenella were detected only when detergent extracts of sonicated sporulated oocysts were used. After chickens were intravenously immunized with a suspension of sonicated sporulated oocyst antigen, cells containing antibodies specific for E. tenella antigens were detected in the red pulp of the spleen. After simultaneous immunoenzyme staining for isotype and antigen specificity, the E. tenella-specific antibody-containing cells were of the IgM isotype after the primary immunization and of the IgM and IgG isotype after the booster immunization. Immune complexes specific for E. tenella on the surfaces of follicular dendritic cells in the germinal centers were also stained. Chickens were also orally infected with sporulated oocysts. In these experiments, cells containing antibodies specific for E. tenella were detected in the lamina propria of the ceca and in the red pulp of the spleen. Specific immune complexes were also detected in the germinal centers of the cecal tonsils. When detergent extracts of sonicated sporulated oocysts were characterized by immunoblotting, rabbit antiserum specific for E. tenella reacted with proteins ranging in size from 16 kDa to 200 kDa, with major bands of 20 kDa, 24 kDa, 45 kDa, and 100 kDa. Monoclonal antibodies specific for E. tenella recognized only proteins of low molecular weight (20 kDa and 24 kDa) or high molecular weight (80-100 kDa). Immune chicken serum reacted with proteins of low and high molecular weight but especially with proteins of 100 kDa and 113 kDa. This method is the first by which immune complexes and cells containing antibodies specific for parasitic antigens can be detected in situ and may be of value for studies of the local humoral immune response to E. tenella in the mucosa of chickens. PMID- 1629611 TI - A simple enzyme-linked immunosorbent assay (ELISA) for the neuron-specific gamma isozyme of human enolase (NSE) using monoclonal antibodies raised against synthetic peptides corresponding to isozyme sequence differences. AB - Monoclonal antibodies specific for the gamma isozyme of human enolase (known as neuron-specific enolase or NSE) have been raised against synthetic peptides after coupling to carrier protein: the selected peptides were those corresponding to regions of amino acid sequence difference between the alpha and gamma subunits of these closely similar isozymes. This technique gave monoclonal antibodies of high specificity and affinity. Two monoclonal antibodies raised against different peptides were used to develop a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA), using one as the solid-phase antibody and the other conjugated to horseradish peroxidase to detect the bound NSE. This assay provides a simple and routine method of detecting NSE in serum samples from patients with small-cell carcinoma of the lung and related tumours. PMID- 1629610 TI - Production of a functional monoclonal antibody recognizing human colorectal carcinoma cells from a baculovirus expression system. AB - The light and heavy chain cDNA of a murine monoclonal antibody (MoAb) with specificity for human colorectal carcinoma cells have been expressed separately, together, and as a dual construct in insect cells infected with recombinant baculoviruses. High levels of the MoAb were expressed under the control of the polyhedrin promoter. The antibody maintained its specific binding to human colorectal carcinoma cells and mediated lysis of these cells by human lymphocytes, monocytes, and murine macrophages, as determined in antibody directed cellular cytotoxicity (ADCC) assays. The recombinant immunoglobulin (Ig), like its ascitic counterpart, did not mediate lysis by either human or rabbit complement. The expression of a recombinant antibody exhibiting both functional binding site and Fc region capacities shows that the baculovirus system could be employed in the production of therapeutic Ig. PMID- 1629612 TI - Fluorometric determination of the DNA content of cells cultured in tissue culture plates. AB - Determining the DNA content of cultured cells with the fluorochrome diaminobenzoic acid (DABA) has been shown to be a sensitive and selective method. A procedure is described which applies this method to cells cultured in 96-well and 24-well plates. After removal of the medium, the cells are disrupted by sonication, dried and reacted with DABA. For the final read-out the DABA-DNA solution is transferred to standard cuvettes and the fluorescence intensity determined with a conventional fluorometer. The method is highly reproducible and suitable for the cell concentrations usually employed in microculture systems. It is an easy non-radioactive method for determining the numbers of both adherent and non-adherent cells, especially when comparing different stages of activation or differentiation. PMID- 1629613 TI - Avidin-binding to peripheral blood B lymphocytes and monocytes. AB - Avidin-coated magnetic beads bind peripheral blood B lymphocytes and monocytes. This unwanted reactivity is not due to the membrane expression of avidin target molecules since beads coated with a biotin-binding analogue are non-reactive and binding occurs even when cellular carbohydrate-binding sites are not active, in the absence of Mg2+ and Ca2+ cations, or when they are blocked by a alpha-D glucose or alpha-D-mannose in presence of Ca2+ and Mg2+. The non-polar residues of avidin appear not to be engaged in a hydrophobic bond with the membrane molecule since suroptimal quantities of serum albumin do not prevent the avidin binding. It is suggested that ionic interactions explain the binding of avidin coated beads to B lymphocytes and monocytes and that these can be inhibited with high molecular weight serum molecules or with 0.4 M NaCl. PMID- 1629614 TI - A modified colorimetric method for the measurement of phagocytosis and antibody dependent cell cytotoxicity using 2,7-diaminofluorene. AB - A sensitive and rapid colorimetric method for the in vitro determination of phagocytic activity and antibody-dependent cell-mediated cytotoxicity (ADCC) is described. The assay uses red blood cells (RBC) as target cells and relies on the specific oxidation of 2,7-diaminofluorene (DAF) by the pseudoperoxidase activity of hemoglobin (Hb). Generation of fluorene blue (FB), the chromophore formed upon oxidation of DAF, was a linear function of erythrocyte concentration. The oxidation of DAF by peritoneal macrophages (M phi) containing myeloperoxidase was negligible, confirming that the development of color was exclusively due to the pseudoperoxidase activity of Hb. A positive correlation was observed between FB formation and increased phagocytosis of opsonized erythrocytes. Phagocytosis increased as a function of time, reaching a maximum at 90 min of incubation. The phagocytosis of IgG-opsonized erythrocytes was greater than non-opsonized erythrocytes and was inhibited by high concentrations of non-specific human or mouse IgG, showing that phagocytosis was mediated by the Fc gamma receptor of macrophages. The interaction between opsonized RBC and macrophages also evoked an antibody-dependent extracellular lysis, however this process was slower than ingestion. The DAF phagocytosis assay has shown to be very sensitive, simple, rapid and safe. PMID- 1629615 TI - A novel B cell stimulation/proliferation assay using simultaneous flow cytometric detection of cell surface markers and DNA content. AB - Assessment of the specific B cell proliferative response by thymidine incorporation following polyclonal stimulation (e.g. with pokeweed mitogen or B cell growth factor) is problematic whenever the proportion of B cells in a particular sample is low as in blood samples. Here we describe a simple assay consisting of identifying the cultured B cells with anti-CD19/CD20 fluorescein conjugated antibody and simultaneously using propidium iodide DNA staining to determine the percent of S/G2/M phase cells among the gated B cells. This assay can be used to determine B cell responsiveness even in individuals with very low blood B cell counts (e.g., in recipients of bone marrow transplant), does not require laborious B cell purifications and does not involve radiation hazard. PMID- 1629616 TI - A polymerase chain reaction assay for the detection and quantitation of cytokine gene expression in small numbers of cells. AB - A reverse transcriptase-polymerase chain reaction (RT-PCR) assay is described that allows the rapid detection and quantitation of mRNA encoding the cytokines interleukin-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma). Analysis of cytokine production by defined CD4+ T cell clones and the thymoma cell line EL4, demonstrates that the oligonucleotide primers used in this assay are specific for the genes encoding the individual cytokines, generating PCR products of different sizes. This allows the simultaneous and unambiguous detection of all three cytokine mRNAs in the same cDNA sample. The assay is sensitive enough to reproducibly detect cytokine mRNA expressed in as few as ten cells and requires 10,000-fold less cells for the detection of IL-2 production than that required for its detection using a conventional bioassay. Reverse transcribed mRNA is quantitated in the PCR assay by amplifying in the presence of a known amount of competitive genomic DNA (gDNA) template containing a small intron using the same primers. The PCR products obtained form the target cDNA and gDNA templates, which are distinguished by size, are processed by Southern analysis and quantitated by scanning densitometry of autoradiographs. As little as two-fold differences in cytokine mRNA can be reliably detected using this assay. We have demonstrated the successful application of this assay to the quantitation of pg amounts of IL-2 mRNA that is constitutively produced at low levels by fetal thymocytes in vivo during T cell ontogeny. The sensitivity, specificity, reliability and speed of this assay will facilitate the analysis of cytokine production in in vivo-derived or, in vitro propagated cells which are not available in sufficient numbers for analysis using more conventional molecular and biochemical assays. PMID- 1629617 TI - A blocking ELISA for the detection of specific antibodies to bovine ephemeral fever virus. AB - A blocking ELISA (B/ELISA) for detecting antibodies to bovine ephemeral fever virus (BEFV) in cattle is described. In this test, the binding capacity of a monoclonal antibody specific for an epitope on antigenic site G1 of the BEF virus glycoprotein is blocked in the presence of positive serum. The sensitivity of the B/ELISA was compared with the virus neutralisation (VN) test using a total of 380 sera from cattle. Of these, 118 were from an area known to be free of bovine ephemeral fever, 181 from naturally and experimentally BEFV-infected cattle, 33 sequential serum samples from a sentinel steer from which Berrimah virus (BERV) had been isolated, 9 from a sentinel cow from which Kimberley virus (KIMV) was isolated and a panel of 39 sera supplied as a blind trial. The B/ELISA results overall compared favourably with those of the VN tests. The monospecificity of the test was demonstrated using hyperimmune mouse ascitic fluid to other BEF serogroup viruses, namely KIM and BER viruses and the results showed no significant cross-reaction. The greater simplicity and sensitivity of the test when compared with the VN test makes it the preferred test for the diagnosis and monitoring of clinical bovine ephemeral fever. PMID- 1629618 TI - A method for the detection of serologically crossreacting antigens both within and between protein mixtures: the western cross blot. AB - The method described in the present paper permits the detection of antigenically related proteins within or between different antigen mixtures. For this purpose two separate SDS-polyacrylamide gels are run (the antigen mixture is applied to the entire width of the gel) and each gel is blotted on to a separate nitrocellulose paper. One sheet ('donor sheet') is incubated with antiserum and placed on to the other blot ('receptor sheet') so that the antigen bands are perpendicular to each other. Subsequently the antibodies from the donor sheet are blotted on to the receptor sheet in alkaline borate buffer containing 1 M NaSCN, which dissociates antigen-antibody complexes. After the removal of the donor sheet the receptor sheet containing the transblotted antibodies is equilibrated in phosphate-buffered saline in order to reconstitute the binding conditions. Antibodies which have bound to receptor antigens during this equilibration period are detected by the use of a peroxidase labelled 2nd antibody. Because each band on the donor sheet crosses each band on the receptor sheet during the transfer, the antibodies from each band of the donor sheet are able to react with each antigen band of the receptor sheet. The validity of the method was established by demonstrating the crossreactivity of a polyclonal antiserum against the intact bovine gamma globulin molecule with the heavy and light chain subunits (and partial reduction products of the molecule) and the absence of crossreactivity between heavy and light chains. In a second experiment crossreacting antigens of different molecular weight were detected within several strains of Escherichia coli. In addition, comparisons of different strains of Escherichia coli revealed crossreacting antigens of identical as well as of different molecular weight. PMID- 1629619 TI - A simple method of concentrating monoclonal antibodies from culture supernatant by ultrafiltration. AB - How to obtain concentrated monoclonal antibodies from culture supernatant is of great importance to many scientists today. In this report, a simple, single-step technique is described to concentrate monoclonal antibodies directly from hybridoma-culture supernatant. The contaminants can be removed from the supernatant by using an ultrafiltration unit which allows macromolecules of less than 100,000 MW to pass through leaving behind monoclonal antibodies which is purified and concentrated more than 25-fold. PMID- 1629620 TI - Factors influencing computer-assisted video image analysis of immunocytochemically stained lymphocytes and macrophages in the spleen of mice. PMID- 1629621 TI - The L929 cell bioassay for murine tumour necrosis factor is not influenced by other murine cytokines. PMID- 1629622 TI - An ELISA utilizing immobilised snowdrop lectin GNA for the detection of envelope glycoproteins of HIV and SIV. AB - A simple, reliable ELISA for the quantitative detection of the envelope glycoproteins of both HIV and SIV is described. It incorporates the snowdrop lectin GNA to capture the glycoprotein antigens and combines the high selectivity of GNA binding with its broad reactivity with the glycoproteins of HIV-1, HIV-2 and SIV. PMID- 1629623 TI - Evaluation of labelled monoclonal antibodies by simultaneous estimation of the association constant, the immunoreactive fraction, and the number of effective binding sites on the specific target. AB - The reaction between a labelled monoclonal antibody (MoAb) and its specific target is characterised by three parameters: the association constant (Ka) of the labelled MoAb, the number (N) of effective binding sites on the specific target, and the immunoreactive fraction (F) of the labelled MoAb preparation. Immunological binding parameters are usually estimated graphically, by fitting the experimental data to linear equations derived from the first order law of mass action (FLMA) at equilibrium. However, only two parameters can be estimated simultaneously in a two-dimensional plot. Consequently, graphical estimation of Ka, F and N must be performed stepwise, using at least two different plots. The three parameters are interdependent, and therefore a stepwise estimation procedure might give suboptimal results. In order to investigate whether this is a problem of practical significance in the evaluation of labelled MoAbs, a computerised iterative nonlinear least squares (INLSQ) method was applied to estimate the three parameters simultaneously. The binding parameters in reactions between different 125I-labelled MoAbs and different types of targets were significantly changed when a graphical procedure was replaced by the computerised INLSQ method, and the goodness of fit to FLMA was improved. Hence, the nonlinear least squares method is the preferred procedure. Values were affected when only a subset of the data was included in the estimation procedure, indicating some heterogeneity even in these presumably homogeneous MoAb reactions. The radiolabelling procedure was presumed to be the main reason for this heterogeneity. PMID- 1629624 TI - Functional innervation of cultured skin grafts. AB - The aims of the present study were to determine 1) if grafts of cultured skin become innervated; and 2) whether tactile function of these grafts could be improved by implanting target tissue into them. Autologous skin equivalents were generated in vitro (30 d) for individual adult Sprague-Dawley rats. Some animals received pure skin equivalent grafts; others had target tissue consisting of 2-mm punch biopsies (normal skin or touch domes) inserted into their skin equivalents at the time of grafting. After 83 d, physiologic recordings were obtained from afferent nerves innervating the grafts. Tissue was processed for histology at various intervals. Silver staining of the tissues demonstrated many isolated nerve fibers in the dermis of cultured areas of skin as well as in implant zones. When grafts were rubbed with a glass rod or pinched with watchmaker forceps, impulses were evoked in nerves innervating both implant and cultured regions. In contrast, the afferent response to gently stroking grafts with a camel hair brush was severely reduced in cultured areas but was vigorous in implanted skin. Neuronal activity characteristic of type I neurons innervating touch domes was only found in cutaneous nerves innervating implants originally possessing domal tissue. Furthermore, grafts with good takes had better return of sensory function than grafts undergoing episodes of crusting. These results suggest that structural components or trophic factors present in implants enhanced the return of neural function related to the sensory modality of light touch; and this was also affected by the engraftment quality. PMID- 1629625 TI - Buschke-Ollendorff syndrome associated with elevated elastin production by affected skin fibroblasts in culture. AB - Buschke-Ollendorff syndrome (BOS; McKusick 16670) is an autosomal dominant connective-tissue disorder characterized by uneven osseous formation in bone (osteopoikilosis) and fibrous skin papules (dermatofibrosis lenticularis disseminata). We describe two patients in whom BOS occurred in an autosomal dominant inheritance pattern. The connective tissue of the skin lesions showed both collagen and elastin abnormalities by electron microscopy. Cultured fibroblasts from both patients produced 2-8 times more tropoelastin than normal skin fibroblasts in the presence of 10% calf serum. Involved skin fibroblasts of one patient produced up to eight times normal levels, whereas apparently uninvolved skin was also elevated more than threefold. In a second patient, whose involvement was nearly complete, elastin production was high in involved areas and less so in completely involved skin. Transforming growth factor-beta 1 (TGF beta 1), a powerful stimulus for elastin production, brought about similar relative increases in normal and BOS strains. Basic fibroblast growth factor, an antagonist of TGF beta 1-stimulated elastin production, was able to reduce elastin production in basal and TGF beta 1 stimulated BOS strains. Elastin mRNA levels were elevated in all patient strains, suggesting that Buschke-Ollendorff syndrome may result, at least in part, from abnormal regulation of extracellular matrix metabolism that leads to increased steady-state levels of elastin mRNA and elastin accumulation in the dermis. PMID- 1629626 TI - Human skin mast cell carboxypeptidase: functional characterization, cDNA cloning, and genealogy. AB - We functionally characterized human skin mast cell carboxypeptidase A (MC-CPA), and explored its evolutionary relationship to other carboxypeptidases to understand further the structural basis for the substrate preferences of this enzyme. Purified human skin MC-CPA displayed more activity than did bovine pancreatic carboxypeptidase A (CPA) against carboxyl-terminal leucine residues, about equal activity with phenylalanine and tyrosine residues, and no activity with tryptophan or alanine. To correlate kinetic data with structure, we isolated and sequenced a cDNA encoding MC-CPA from human skin, and directly sequenced 30% of the purified protein. These sequences agreed with that of human lung MC-CPA, and further support the evidence for a single MC-CPA gene in humans. Four amino acid replacements, resulting in a net positive change in non-hydrogen atoms in the S1' subsite of MC-CPA, were associated with less alteration in substrate specificity, relative to bovine CPA, than might be expected from studies using rat CPA1 and CPA2. We noted two consensus N-linked glycosylation sites in human MC-CPA that are not found in rat and mouse MC-CPA, or in bovine CPA; that at least one of these sites is glycosylated in vivo was verified by N-glycosidase F treatment, lentil lectin binding, and Concanavalin A-Sepharose chromatography. Evolutionary trees constructed from the known carboxypeptidase sequences suggested that MC-CPA most likely evolved from a carboxypeptidase B-like enzyme, independent of the pancreatic CPA. Thus, in the carboxypeptidase gene family, MC CPA displays a unique genealogy and several amino acid replacements in its S1' binding pocket that result in substrate specificity quite similar to bovine CPA. PMID- 1629627 TI - Comparative histochemistry of port-wine stains after copper vapor laser (578 nm) and argon laser treatment. AB - The present study compared the histologic changes occurring 15 min after copper vapor laser (CVL; operating at 578 nm) and argon laser (488/514 nm) treatment of port-wine stains (PWS) over a range of energy densities (8-32 J/cm2) with corresponding pulse widths of 50-200 ms. Frozen tissue sections were stained with nitroblue tetrazolium chloride (NBTC). This histochemical method permits an accurate color differentiation between blue-stained viable and unstained thermally damaged cells. At 8, 10, and 12 J/cm2 the argon-laser injury was confined to epidermal cell layers; none to superficial dermal effects were found. Fluences of at least 15 J/cm2 produced a diffuse NBTC-negative coagulation necrosis. Exposure of PWS skin to 8-12 J/cm2 at 578 nm did not alter the integrity of epidermal cells. In the dermis, damage was confined to blood vessels and surrounding collagen, showing a clear demarcation from adjacent viable structures. The maximum penetration depth achieved with these vessel selective energy densities was 0.44 mm. At 15 J/cm2, besides vascular injury, damage to the basal cell layer also occurred. At fluences of 17-20 J/cm2 a diffuse necrosis similar to that induced by the argon laser was found. Vessel selectivity of the 578 nm wave band was achieved with pulse widths from 50-74 ms, exceeding the estimated "ideal" exposure time (0.1-10.0 ms) for a vascular selective laser effect. The NBTC method allowed identification of subtle laser-induced tissue changes providing accurate quantitative data relating to the extent of vascular injury. PMID- 1629628 TI - Increasing epidermal growth factor receptor expression in human melanocytic tumor progression. AB - Different results have been reported on the expression of epidermal growth factor receptor (EGFR) in human melanocytic lesions, which may be due to different methodologic approaches. Therefore, we compared EGFR expression in six human melanoma cell lines by utilizing the monoclonal antibodies 2E9, 425, and 225, applying four immunocytochemical staining procedures. The results were compared with those obtained by a multiple point ligand binding assay. In addition, Northern blot analysis was performed. A three-step immunoperoxidase method using the monoclonal antibody 2E9 proved most sensitive. Staining intensities, estimated semiquantitatively, correlated well with the quantitative data obtained by the ligand-binding assay. Expression on the mRNA level was also in agreement with these results. Immunohistochemical staining of a large series of human cutaneous melanocytic lesions using the method selected showed differential EGFR expression in various stages of melanocytic tumor progression: 19% of common nevocellular nevi; 61% of dysplastic nevi, 89% of primary cutaneous melanomas, and 91% of melanoma metastases showed staining of the melanocytic cells. Intralesional heterogeneity of EGFR expression was present. Although the mean percentage of positive melanocytic cells in positive lesions did not increase with progression, mean staining intensity was stronger in malignant lesions compared to benign lesions. Ligand binding assays showed that EGFR expression in the highly metastasizing cell lines MV3 and BLM was at least 40 times higher than in the cell lines IF6, 530, M14, and Mel57, which do not or only sporadically metastasize after subcutaneous inoculation in nude mice. Although the differences between the various stages of progression are not absolute, we provide further evidence that EGFR expression increases in human melanocytic tumor progression. PMID- 1629629 TI - The major cicatricial pemphigoid antigen is a 180-kD protein that shows immunologic cross-reactivities with the bullous pemphigoid antigen. AB - Recent studies have shown that sera from patients with cicatricial pemphigoid (CP) contained autoantibodies against epidermal antigens of molecular weight 230 kD and/or 180 kD by immunoblotting, similar to those recognized by bullous pemphigoid (BP) sera. Previous immunoprecipitation studies have shown that BP sera only precipitated the 230-kD antigen. To characterize the CP antigen(s) we tested 10 CP sera, 10 BP sera, and four controls by both immunoprecipitation of radiolabeled cells and immunoblotting of epidermal extracts. For immunoprecipitation, we used 0.5% NP-40 extracts of both normal human keratinocytes and Pam cells. All CP sera precipitated a 180-kD protein that co migrated with the BP180 antigen precipitated by some individual BP sera. Two of these CP sera also faintly bound a 230-kD protein of similar molecular weight as the major BP230 antigen. CP and BP sera with an immunoblotting pattern of 180 kD immunoprecipitated a co-migrating 180-kD protein. CP sera reacting by immunoblotting with the 230-kD antigen precipitated the 180-kD and/or the 230-kD antigen. In contrast, BP sera reacting with the 230-kD antigen only precipitated this antigen. In further experiments, labeled 0.5% NP-40 extracts from Pam cells were first preabsorbed with a reference BP serum and then immunoprecipitated with CP sera. Under these conditions, CP sera that immunoprecipitated both 180-kD and 230-kD proteins with the standard procedure no longer precipitated these proteins. Our results suggest that a 180-kD protein is the major CP target antigen that demonstrated immunologic cross-reactivities with the BP180 and the BP230 antigens. PMID- 1629630 TI - Stereologic estimation of volume-weighted mean nuclear volume as a predictor of prognosis in "thin" malignant melanoma. AB - At present, tumor invasion represents the most reliable prognostic factor for primary malignant melanoma. The 10-year survival rate of "thin" melanomas (Breslow less than 0.76 mm) is more than 95%, but approximately 5% of these low risk tumors do metastasize. In an attempt to determine prognostic markers for "thin" melanomas we investigated the volume-weighted mean nuclear volume (Vv) of primary melanomas with tumor invasions below 0.76 mm in 32 patients. Ten of these patients had developed melanoma metastases within a mean follow-up period of 49 months; 22 patients who had not developed metastases and who were comparable with regard to clinical and histologic criteria as well as to follow-up period were selected as a comparison group. Vv was determined by computer-assisted image analysis (IBAS 20, Kontron, Germany) on hematoxylin-eosin-stained sections employing stereologic estimation of the volume-weighted mean nuclear volume. In addition, two-dimensional morphometric parameters (nuclear area and shape factors) as well as clinical (sex, age, location) and histologic characteristics (Breslow's thickness, Clark's level, and growth patterns) were recorded. The mean Vv (+/- SD) of primary melanomas with subsequent metastatic course was 273 microns 3 (+/- 81.3), whereas primary melanoma lesions without subsequent metastases exhibited a significantly lower Vv of 154 microns 3 (+/- 25.3) (p = 0.0008). On the other hand, two-dimensional morphometric and clinical and histologic parameters did not correlate with prognosis. Vv thus seems to represent a powerful and independent prognostic marker for "thin" primary melanomas. Assessment of Vv may provide a valuable tool in selecting patients with high-risk stage I, Breslow less than 0.76 mm, melanoma for adjuvant therapy. PMID- 1629631 TI - Effects of multiple applications of tumor promoters and ultraviolet radiation on epidermal proliferation and antioxidant status. AB - The dorsal skin of hairless mice (Skh:HR-1) was treated with multiple applications of acetone, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or ethyl phenylpropionate (EPP) two times per week, or exposed to ultraviolet radiation (UVR) three times per week for treatment periods up to 16 weeks. Epidermal hyperplasia, as measured by epidermal thickness, was increased in all three treatment groups after a single (0.5 weeks) TPA, EPP, or UVR treatment. TPA- and EPP-induced hyperplasia had begun to subside by 16 weeks, whereas UVR-induced hyperplasia was still increasing at that point. Epidermal homogenates were examined for ornithine decarboxylase (ODC) activity 6 h after the final treatment at 0.5, 2, 8, and 16 weeks of treatment. ODC activity was elevated in all treatment groups (TPA greater than EPP greater than UVR), with UVR induction returning to near control (acetone) levels by 16 weeks even though the UVR induced hyperplasia continued to increase at the 16-week point. Homogenates examined for superoxide dismutase (SOD), catalase (CAT), and xanthine oxidase (XO) activity 48 h after the final treatment at 0.5, 2, 4, 8, 12, and 16 weeks had decreased activities of both SOD and CAT. TPA and EPP elevated XO, but UVR had little or no effect. Our data indicate that promoter-induced hyperplasia persists for extended periods of time and that diminution of antioxidant defenses observed following prolonged tumor-promoter treatment persists through the time period when tumors would be expected to begin. This antioxidant diminution may be one of a cascade of events that leads to epidermal proliferation and tumor promotion in mouse skin. PMID- 1629632 TI - Enhanced production of plasminogen activator activity in human and murine keratinocytes by transforming growth factor-beta 1. AB - Transforming growth factor-beta (TGF beta) is the most potent known inhibitor of keratinocyte growth. Pericellular proteolytic activity is usually high in proliferating and malignant cells and decreased in resting or growth-arrested cells. We have therefore analyzed the effects of TGF beta 1 on the production of plasminogen activator activity by normal human keratinocytes and a mouse keratinocyte cell line under serum-free conditions. The plasminogen activator activity of the culture medium was analyzed using caseinolysis-in-agar and zymography assays, immunoblotting, and Northern hybridization analysis for the plasminogen activators (PA) and PA inhibitor-1 (PAI-1). Alterations of radiolabeled polypeptides were observed in fluorograms of gels. It was found that like in human epidermoid carcinoma cells picomolar concentrations of TGF beta 1 (0.2-20 ng/ml) enhanced total plasminogen activator activity in both keratinocyte cell systems. Zymographic and immunoblotting analyses of the medium indicated that the activator was of the urokinase type (u-PA). Immunoprecipitation and Concanavalin A affinity chromatography of the culture medium indicated that the cells also started to produce PAI-1. Analysis of the pericellular matrix preparations of the keratinocytes showed that PAI-1 is deposited to the pericellular space. Evidently due to elevated u-PA activity PAI-1 was removed from the extracellular matrix more rapidly in TGF beta 1-treated cells than from control cultures. Northern hybridization analysis of human keratinocytes showed that TGF beta 1 rapidly elevated both u-PA and PAI-1 mRNA levels. Comparison of the temporal induction profiles indicated that the mRNA for u-PA increased more slowly but was more persistent than that of PAI-1. Actinomycin D inhibited the induction of both u-PA and PAI-1 mRNA, suggesting that the induction was due to increased transcription. The results suggest that enhanced plasminogen activator activity can be associated with growth inhibition also in nonmalignant cells like cultured human or murine keratinocytes. PMID- 1629633 TI - Epidermal HMG CoA reductase activity in essential fatty acid deficiency: barrier requirements rather than eicosanoid generation regulate cholesterol synthesis. AB - We showed previously that the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting enzyme of cholesterol biosynthesis, increases after both barrier disruption with organic solvents and in essential fatty acid deficiency (EFAD). Here, we treated EFAD hairless mice with linoleic acid, columbinic acid (C18: 3, n-6, trans; not metabolizable to known regulatory eicosanoids), prostaglandin E2 (PGE2), or latex occlusion, and determined transepidermal water loss (TEWL), epidermal protein content, and epidermal HMG CoA reductase activity. Increased TEWL rates in EFAD were accompanied by increased HMG CoA reductase activity (+130%, n = 6, p less than 0.01) and protein content (+69%; n = 6, p less than 0.025). Artificial restoration of the barrier by occlusion reduced the increase in enzyme activity and protein content toward normal, but barrier function, measured immediately after removal of the latex wrap, deteriorated further (TEWL: two-fold greater than EFAD unoccluded; p less than 0.01). Topical applications of either linoleate or columbinate (but not PGE2), normalized barrier function, HMG CoA reductase activity, and protein content. These results show that a) barrier function modulates HMG CoA reductase activity; b) reduction of cholesterol synthesis with occlusion results in a further deterioration in barrier function, suggesting that increased synthesis is a protective homeostatic response; and c) the barrier abnormality reflects a requirement for specific fatty acids for the barrier rather than resulting from epidermal hyperplasia or decreased prostaglandin generation. PMID- 1629634 TI - Relationship between cholesterol sulfate and intercellular cohesion of the stratum corneum: demonstration using a push-pull meter and an improved high performance thin-layer chromatographic separation system of all major stratum corneum lipids. AB - To investigate the role of cholesterol sulfate (CS) as an intercellular glue or cement in the stratum corneum, we compared the relationship between CS levels and magnitude of the intercellular cohesion of the stratum corneum between the palm and the upper arm. Using a push-pull meter, the palm displayed approximately seven times the magnitude of cohesion of the stratum corneum as the upper arm (n = 11). CS and other stratum corneum lipids were extracted from the palm and the upper arm (n = 22) by a cup method and determined by our improved high performance thin-layer chromatography (HPTLC). Despite a great difference in the magnitude of cohesion (p less than 0.01), CS levels and ratios of CS to ceramides and CS to cholesterol in the stratum corneum showed no significant differences between the palm and the upper arm. Our results suggest that differences in CS cannot account for the differences in cohesion between palm and upper arm. PMID- 1629635 TI - Purification of functional active epidermal Langerhans cells: a simple and efficient new technique. AB - Our knowledge of the functional activity of the epidermal Langerhans cell has been severely hampered by the lack of an easy method of purification of these cells that is both efficient and reproducible. In the present study we have used immunomagnetic beads directly conjugated to an IgM class mouse anti-human human leukocyte antigen DR monoclonal antibody to positively select human Langerhans cells from an epidermal cell suspension. Cells were then treated with a high affinity polyclonal anti-mouse immunoglobulin that detached the beads by competing with the antigen for the antigen-binding site on the monoclonal antibody. This procedure allowed removal of the immunomagnetic beads, leaving Langerhans cells free from bound antibody. Recovery of Langerhans cells ranged from 40 to 80% of the starting number of Langerhans cells. The resulting cells were up to 99% CD1a positive and showed potent functional activity in the allogeneic mixed epidermal cell - lymphocyte reaction. Keratinocytes were shown to exert a profound inhibitory effect on Langerhans cell function that could not be prevented by indomethacin. This method is technically simple and allows good recovery of a highly purified population of Langerhans cells that are functionally active. PMID- 1629636 TI - Quantitative 111In antimyosin antibody imaging to predict the age of myocardial infarction. AB - To establish whether quantitative 111In antimyosin uptake can be used to predict infarct age, we studied the heart-lung ratio in 107 images from 90 patients at various intervals following a Q-wave infarction. Imaging was performed 24 hours following 111In antimyosin injection. The HLR was measured as the ratio of the maximum counts in the infarcted myocardium to the adjacent lung background. The ratio ranged from 1.26 to 3.87, and declined with increasing infarct age. Infarcts were classified on the basis of age as type I (less than 3 days old), type II (less than 14 days), and type III (less than 90 days). True positive and false positive rates (TPR and FPR), and test-likelihood ratio calculations were performed for HLR thresholds ranging from 1 to 4, for the three infarct types. A FPR of 0% and likelihood ratio of infinity was obtained at a HLR threshold of 2.3 for type I infarcts (TPR 40.8%); at a HLR threshold of 2 for type II infarcts (TPR 50.6%), and a threshold of 1.8 for type III infarcts (TPR 52.6%). The likelihood of each infarct type can be estimated directly from the HLR for values below the above thresholds. These results show that quantitative 111In-antimyosin imaging may be used to predict infarct age. PMID- 1629637 TI - Improvement of digital coronary angiography: high resolution processing coupled with a real time functional synchronization procedure. AB - The use of Digital Subtraction Angiography in coronary applications is restricted by the difficulty in: 1. Obtaining a good resolution of the distal branches. 2. Avoiding, for the purpose of subtraction, the motion artifacts induced by artery and background displacement during the cardiac and respiratory cycles. 3. Preserving the dynamic vascular motion. 4. And storing the digital dynamic information on a permanent support. We used for this study an angiography system, based upon a high resolution 45 MIPS-32 Mbyte image processor, interfaced with a 2.75 Gbyte Winchester drive allowing the real time storage of either 30 frames/s in the 512*512*8 bits matrix or of 7.5 f/s in the 1024*1024*8 bits matrix. To preserve the most important dynamic informations on the basis of the 7.5 f/s maximal storage rate, we developed a synchronization device able to recognize in real time, from chronologic delays derived by using both ECG and Aortic Pressure curves, the functional End-Diastolic (ED) and the End-Systolic (ES) positions, even in the case of heart rates varying during the procedure. The ED and the ES images are stored together with the Mid-Systolic (MS), the 1/3-Diastolic (1/3D) and 2/3-Diastolic (2/3D) images. To establish the validity of this sampling method, which uses a reduced number of frames per cardiac cycle, 7200 coronary injections performed during 450 routine coronary angiographies were compared by two independent observers (A and B), using: first a Digital (D) 5 frames/cycle sequence, and secondly a cine Film (F) 50 frames/s sequence acquired immediately after the corresponding D injection. The D technique resulted in the best image and diagnostic quality, particularly when the F quality was estimated 'fair' or 'poor' by both observers, and in an important reduction on X-Ray doses. The visualisation of the sequential ED, MS, ES, 1/3D and 2/3D frames gives the possibility: 1. of saving the dynamic information, as a regular sample of functional images can be displayed with a cine loop technique. 2. of facilitating cardiac synchronized subtractions. 3. of reducing the amount of frames per cycle, thus allowing an important reduction of X-ray doses and the digital and permanent storage of the most important cardiac cycles. PMID- 1629638 TI - Morphometry versus densitometry--a comparison by use of casts of human coronary arteries. AB - Geometric and densitometric methods for quantitative coronary arteriography have generally been compared by use of phantoms simulating arteries with circular lumina ('Hole phantoms'). We have used more adequate phantoms obtained by casting disease-free and atheromatous human coronary arteries. The phantoms, filled with contrast medium, were imaged digitally (1024 x 1024 x 10 matrix) under experimental conditions simulating routine coronary angiography. The angiographic 'diameters' and the densitometric cross-sectional areas of 59 marked lumina were determined in single plane and orthogonal biplane raw images. Geometric calibration was performed by help of a 7F coronary catheter. For the densitometric calibration, we used a 'hole phantom' attached to the image intensifier. The obtained luminal areas were compared to their true values determined previously by planimetry. The mean absolute error of single plane cross-sections obtained geometrically was 1.53 mm2. Biplane imaging reduced it by a factor 2.4 to 0.64 mm2. The corresponding mean absolute errors for densitometry were 0.56 mm2 and 0.51 mm2. Single plane 'diameter' measurements appear thus of very limited value for hemodynamic conclusions. In contrast, biplane geometric quantification was not markedly inferior to single plane and biplane densitometry. PMID- 1629639 TI - The clinical usefulness of electrocardiogram-gated Tc-99m methoxy-isobutyl isonitrile images in the detection of basal wall motion abnormalities and reversibility of stress induced perfusion defects. AB - Technetium-99m methoxy-isobutyl-isonitrile (SESTAMIBI) has been recently introduced to trace regional myocardial perfusion. Beyond blood flow distribution, a quantitative index of regional myocardial wall motion from SESTAMIBI electrocardiogram (ECG)-gated images was obtained, according to the assumption that changes in the detected radioactivity reflect changes in myocardial wall thickness during the cardiac cycle. As a preliminary study, 20 patients with coronary artery disease and regional wall motion abnormalities and 15 normal subjects were studied by SESTAMIBI scintigraphy and contrast ventriculography. Regional wall motion was analyzed by a radial method applied to both techniques. Absolute systolic changes in radioactivity and its ratio to reference normal values (wall thickening index, WTI) were determined in 9 anatomical cardiac regions according to the formula (endsystolic counting profile enddiastolic counting profile/enddiastolic counting profile) x 100. The overall agreement between radioisotopic and ventriculographic techniques was 88% (158 of 180 segments). Normal, hypokinetic and akinetic ventriculographic segments showed WTI values of 1.1 +/- 0.2, 0.8 +/- 0.2 and 0.4 +/- 0.3 respectively (P less than 0.001). A second clinical study was performed in 25 patients studied by stress/rest ECG-gated SESTAMIBI scintigraphy. The assumption of this part of the study was to investigate if a preserved wall thickening in segments with stress defects might predict those areas with normal resting perfusion. Partial or total normalization of regional perfusion was observed in 90% of segments with a WTI greater than or equal to 0.8. These studies indicate the ECG-gated SESTAMIBI may represent a suitable technique for the simultaneous analysis of flow distribution and function. Analysis of post-exercise ECG-gated SESTAMIBI can predict the reversibility of transient perfusion defects. PMID- 1629641 TI - Angiographic assessment of dimensions of 6F and 7F Mallinckrodt Softouch coronary contrast catheters from digital and cine arteriograms. AB - Coronary contrast catheters are almost exclusively used for calibration purposes in quantitative coronary arteriography. In this study we have assessed the suitability of new 6F and 7F Mallinckrodt nylon catheter with Softouch tip with improved imaging specifications for such calibration purposes both from digital and cinefilm images using new analytical QCA-software packages (Philips DCI/ACA and Medis CMS). The average signed differences between the angiographically measured dimensions at 100% contrast fillings and acquired at 3 different kV levels (60, 75 and 90 kV) were -3.3% and 0.6% for the 6F and 7F catheter tips, respectively as measured with the ACA-package on digital images, and -0.4% and 2.1%, respectively, as measured with the CMS-system on cinefilm images. The pooled standard deviations were 0.102 mm and 0.107 mm for the 6F and 7F catheter tips, respectively, as measured with the ACA-package, and 0.080 mm and 0.083 mm, as measured with the CMS-system. The deviations for the nylon shafts were much larger. It became also clear that neither the filling of the catheters, nor the kV-level used, had any appreciable effect on the measurement accuracy for the Softouch tips, which facilitates the frame selection in QCA-studies. From these data it can be concluded that the nontapering parts of the 6F and 7F Mallinckrodt Softouch tips are very well suitable for QCA calibration purposes, but that the nylon shafts are not. PMID- 1629640 TI - Diagnostic value of transesophageal echocardiography in atrial septal aneurysm. AB - Transthoracic and transesophageal echocardiography was performed in 40 consecutive adult patients with an atrial septal aneurysm. In 11 (27%) of 40 patients transthoracic echocardiography failed to demonstrate the lesion and the diagnosis was established by the transesophageal approach only. Interatrial shunting, assessed by echocardiographic contrast study and/or color flow mapping, was detected in 13 (54%) of 24 patients on transthoracic imaging and in 29 (76%) of 38 patients during transesophageal echocardiography. Identification of multiple fenestrations (n = 9) and thrombi within the aneurysm (n = 2) could be achieved only by transesophageal ultrasound. A cerebrovascular event of suspected embolic origin occurred in 20 (50%) of 40 patients; 11 (55%) of the 20 patients had repeated cerebral events. Except for mitral valve prolapse in 2 patients and spontaneous left atrial contrast phenomenon in 1 patient no other potential cardiac source of embolism could be identified by transesophageal echocardiography. A marked thickening of the aneurysm was present in 14 (70%) of 20 patients with a cerebrovascular event versus only 4 (20%) of 20 patients without a cerebrovascular event (p less than 0.01). The mechanism of embolization may be both primary thrombus formation within the aneurysm and paradoxical embolization through an interatrial communication as suggested by the findings on transesophageal ultrasound in 2 patients. Although the patients of this study represent a highly selected group it may be concluded that atrial septal aneurysm is a cardiac abnormality with embolic potential. Transesophageal echocardiography has to be regarded the imaging method of choice for evaluation of this lesion. PMID- 1629642 TI - Impact of changes in heart rate and stroke volume on the cross sectional flow velocity distribution of diastolic mitral blood flow. A study on 6 patients with pacemakers programmed at different heart rates. AB - The effect of changes in stroke volume on the cross sectional velocity distribution in the mitral orifice during passive mitral inflow was studied in six patients with total atrioventricular block, atrial fibrillation and VVI pacemakers during periods with different heart rates. The time velocity integrals recorded both in the left ventricular outflow tract and at the mitral orifice decreased significantly as the heart rate was increased from 60 to 80 and from 80 to 100 beats per minute. Instantaneous cross sectional flow velocity profiles were constructed by time interpolation of the velocity data from each point in sequentially delayed two dimensional digital ultrasound maps. Each patient had a characteristic cross sectional flow velocity profile in the mitral orifice recorded at the level of the leaflet tips in a four chamber view. The velocity profiles varied between the patients. With increase in heart rate only minimal changes in the flow profiles from individual patients were seen. The maximum velocity through the mitral orifice overestimated the cross sectional mean velocity at the same time by a factor of 1.4-1.9. The maximum time velocity integral overestimated the cross sectional mean by a factor of 1.4-1.8. The observed cross sectional skew varied between patients but did not change significantly with increasing heart rate and decrease in stroke volume. PMID- 1629643 TI - Identification of coronary artery by-pass grafts: reliability of MRI in clinical practice. AB - In order to test MRI ability to detect the number and the sites of coronary artery by-pass grafts (CABGs), 22 patients with CABGs were studied. The detection of a neo-vessel in even one of the examination slices was considered as positive for the study, disregarding the difference between its origin and course. With such a criterion, MRI total percentage of vascular bridges identification resulted in 76.1% (51/67) with very low values for CABGs implanted on diagonal, obtuse marginal and posterior descending vessels (11/24 = 45.8%). These results lead to the conclusion that, although MRI has some advantages in the identification of CABGs implanted on the main coronary vessels in the early post operative period, its extensive use cannot be proposed at the present state of the art. PMID- 1629644 TI - Myocardial volume perfused by coronary artery branches--a three-dimensional x-ray CT evaluation in human cadaver hearts. AB - The volume of myocardium perfused by coronary arterial branches and cumulative length of the main feeder branches perfusing that volume were measured from multislice computed tomography images of human cadaver hearts with barium sulfate gel injected into the coronary arteries. Previously we have shown in in vivo pig hearts that the relationship between the volume (V), in mL, of perfused myocardium and the length (L), is well conveyed by V = M x 10(-aL) where M is total mass of myocardium perfused by a major epicardial artery and a is constant congruent to 0.01 mm-1. In the nine human hearts studied, this relationship was V = 115 x 10(-0.006L), r = -0.894 for the LAD; V = 48 x 10(-0.009L), r = -0.7663 for the LCX and V = 103 x 10(-0.004L), r = -0.673 for the RCA. These results suggest that the angiographically delineated volume of myocardium at risk of infarction, due to acute blockage along a coronary artery, could possibly be estimated from the 3D branching geometry of the epicardial coronary arterial tree. PMID- 1629645 TI - [The manpower study of thoracic and cardiovascular surgery in Western countries- comparison with Japan]. PMID- 1629646 TI - [Open heart surgery in the first month of life]. PMID- 1629647 TI - [Long-term follow up after repair of complex heart anomalies]. PMID- 1629648 TI - [Care and mechanical cardiac support for severe heart failure associating acute myocardial infarction and open heart surgery]. PMID- 1629649 TI - [Evaluation and management of advanced lung cancer]. PMID- 1629650 TI - [Esophageal reconstruction]. PMID- 1629651 TI - [Coronary artery reoperation]. PMID- 1629652 TI - [To improve the operative results of aortic arch repair]. PMID- 1629653 TI - [Tracheal and carinal reconstruction]. PMID- 1629654 TI - [Dissection of lymph nodes and extended operative intervention in the surgical management of esophageal carcinoma]. PMID- 1629655 TI - [Repair of complex heart anomalies]. PMID- 1629656 TI - Drosophila single-minded gene and the molecular genetics of CNS midline development. AB - Our goal is to understand the molecular mechanisms that govern the formation of the central nervous system. In particular, we have focused on the development of a small group of neurons and glia that lie along the midline of the Drosophila CNS. These midline cells possess a number of unique attributes which make them particularly amenable to molecular, cellular, and genetic examinations of nervous system formation and function. In addition, the midline cells exhibit distinctive ontogeny, morphology, anatomical position, and patterns of gene expression which suggest that they may provide unique functions to the developing CNS. The single minded gene encodes a nuclear protein which is specifically expressed in the midline cells and has been shown to play a crucial role in midline cell development and CNS formation. Genetic experiments reveal that sim is required for the expression of many CNS midline genes which are thought to be involved in the proper differentiation of these cells. In order to identify additional genes which are expressed in some or all of the midline cells at different developmental stages, a technique known as enhancer trap screening was employed. This screen led to the identification of a large number of potential genes which exhibit various midline expression patterns and may be involved in discrete aspects of midline cell development. Further molecular, genetic, and biochemical analyses of sim and several of the enhancer trap lines are being pursued. This should permit elucidation of the genetic hierarchy which acts in the specification, differentiation, and function of these CNS midline cells. PMID- 1629657 TI - Developmental regulation of ecdysteroid receptors in the nervous system of Manduca sexta. AB - The technique of steroid hormone autoradiography has been used to study the cellular distribution of ecdysteroid binding sites in the ventral nervous system of the tobacco hornworm moth, Manduca sexta. The ligand was 26 [125I]iodoponasterone. Tissue was examined from the subesophageal ganglia, thoracic ganglia, and abdominal ganglia of larvae at two times during the larval pupal transient: the 2nd day of wandering and the prepupal stage. The patterns of neuronal binding seen were compared with those found in earlier autoradiographic studies of hormone binding in tissue sampled on the 1st day of wandering, in the pharate adult, and in the 4-day-old moth (Fahrbach and Truman, '89). The pattern of binding was reproducible but dependent upon developmental stage: whereas only a subset of neurons exhibited nuclear accumulation of radiolabeled ecdysteroids on the 1st day of wandering, less than 24 hours later nearly every neuron in the ventral nervous system was labeled. A limited pattern of binding, however, was seen again in the prepupal nervous system. Thus, the insect nervous system is able to use a single hormone both as a general cue for metamorphic development and as a single targeted to stage-specific subsets of neurons by alternating periods of ubiquitous expression of receptor with periods during which the capacity to bind the steroid hormone is highly restricted. PMID- 1629658 TI - Specificity of VIIIth nerve regeneration in lower vertebrates. AB - From the initial studies of Sperry (Am. J. Physiol, 144:735-741, 1945) to more recent investigations, the regenerative capacity of the VIIIth cranial nerve in nonmammalian vertebrates has been noted for its robust and accurate recovery of functional connections after transection. The VIIIth cranial nerve contains nerve fibers that link functionally distinct sensory epithelial to various areas within the central nervous system (CNS), yet after transection these multiple components of the nerve navigate back to their original central target areas, without innervating inappropriate nuclei. A number of factors may be required to establish and direct VIIIth nerve regeneration. Cellular interactions appear to be necessary for the initiation of outgrowth and the maintenance of neural connections. The release of chemotropic substances from target cells has been postulated as the most likely mechanism guiding the reinnervation of central targets. Furthermore, the growth characteristics of these neurons in tissue culture, without target cells present, indicates that intrinsically regulated growth features may also contribute to the process of VIIIth nerve regeneration. PMID- 1629659 TI - Development of spinal motor networks in the chick embryo. AB - We have examined the cellular and synaptic mechanisms underlying the genesis of alternating motor activity in the developing spinal cord of the chick embryo. Experiments were performed on the isolated lumbosacral cord maintained in vitro. Intracellular and whole cell patch clamp recordings obtained from sartorius (primarily a hip flexor) and femorotibialis (a knee extensor) motoneurons showed that both classes of cell are depolarized simultaneously during each cycle of motor activity. Sartorius motoneurons generally fire two bursts/cycle, whereas femorotibialis motoneurons discharge throughout their depolarization, with peak activity between the sartorius bursts. Voltage clamp recordings revealed that inhibitory and excitatory synaptic currents are responsible for the depolarization of sartorius motoneurons, whereas femorotibialis motoneurons are activated principally by excitatory currents. Early in development, the dominant synaptic currents in rhythmically active sartorius motoneurons appear to be inhibitory so that firing is restricted to a single, brief burst at the beginning of each cycle. In E7-E13 embryos, lumbosacral motor activity could be evoked following stimulation in the brainstem, even when the brachial and cervical cord was bathed in a reduced calcium solution to block chemical synaptic transmission. These findings suggest that functional descending connections from the brainstem to the lumbar cord are present by E7, although activation of ascending axons or electrical synapses cannot be eliminated. Ablation, optical, and immunocytochemical experiments were performed to characterize the interneuronal network responsible for the synaptic activation of motoneurons. Ablation experiments were used to show that the essential interneuronal elements required for the rhythmic alternation are in the ventral part of the cord. This observation was supported by real-time Fura-2 imaging of the neuronal calcium transients accompanying motor activity, which revealed that a high proportion of rhythmically active cells are located in the ventrolateral part of the cord and that activity could begin in this region. The fluorescence transients in the majority of neurons, including motoneurons, occurred in phase with ventral root or muscle nerve activity, implying synchronized neuronal action in the rhythm generating network. Immunocytochemical experiments were performed in E14-E16 embryos to localize putative inhibitory interneurons that might be involved in the genesis or patterning of motor activity. The results revealed a pattern similar to that seen in other vertebrates with the dorsal horn containing neurons with gamma-aminobutyric acid (GABA)-like immunoreactivity and the ventral and intermediate regions containing neurons with glycine-like immunoreactivity. PMID- 1629660 TI - Functional regeneration and recovery of locomotor activity in spinally transected lamprey. AB - Spinally transected lamprey recovery locomotor function within 3-6 weeks, and recovery is due, in part, to functional regeneration of neural pathways in the central nervous system (CNS). Our data demonstrate for the first time in the lamprey that descending axons arising from brainstem command neurons can functionally regenerate and restore locomotor initiation below a healed spinal transection site. Immediately after behavioral recovery (3-6 weeks) the locomotor pattern was incomplete but returned to normal during the remainder of the recovery period (6-40 weeks). Initially, the extent of regeneration of descending axons was limited but increased to at least 30-50 mm at recovery times of 24-40 weeks. Regenerated giant Muller axons do not contribute significantly to recovery of locomotor function; rather, regenerated axons of smaller reticulospinal neurons appear to restore locomotor initiation. The restoration of locomotor coordination across a spinal lesion is dependent on two mechanisms: regeneration of spinal coordinating neurons and mechanosensory inputs. Comparisons are made to spinal cord regeneration in other lower vertebrates and to the relative lack of CNS regeneration and behavioral recovery in higher vertebrates. PMID- 1629661 TI - Early innervation of abdominal swimmeret muscles in developing lobsters. AB - The swimmerets in the abdomen of the lobster Homarus americanus are paired external appendages whose back and forth propulsive movements are brought about largely by a group of power and return stroke muscles located in the lateral abdominal cavity. We find functional innervation of these muscles by several excitatory axons and a single inhibitor in embryonic and stage 1 larval lobsters before the external appendages are even formed. This early innervation is via a few nerve bundles in which branches of the motor axons are intertwined in a complex manner. As the swimmerets develop to maturity in later larval and juvenile stages, the innervation consisting usually of several excitor and a single inhibitor synaptic terminals becomes localized to individual muscles. Patterned synaptic activity in these muscles was not seen in the embryonic and larval stages but has been shown in early juvenile stages, when it coincides with the onset of rhythmic movement of the swimmerets. Consequently, such early innervation of the swimmeret muscles may be influential in establishing the central circuitry for the generation of patterned activity, a possibility that was discounted in a previous study (Proc. Natl. Acad. Sci. USA, 70:954-958). PMID- 1629662 TI - Molecular mechanisms of axon guidance in the developing insect nervous system. PMID- 1629663 TI - The mechanism of suckling in two species of infant mammal: miniature pigs and long-tailed macaques. AB - Suckling is the form of feeding unique to infant mammals. The mechanism used by infant mammals to withdraw liquid from the nipple is the subject of considerable debate. Suckling has been examined in two species of infant mammals: miniature pigs and long-tailed macaques. In both species radio-opaque markers were inserted into the tongue and jaws; the movements of the jaw and tongue (and also of specific regions within the tongue) plus the movement of milk containing barium were studied by high-speed cineradiography (100 and 150 frames/sec). In the case of macaques, simultaneous pressure transducer recordings were also made. In both species, liquid moved out of the nipple as the intraoral space was expanded by a combination of tongue movement (negative pressure pumping) coupled with jaw opening. There was no evidence for expression (positive pressure on the nipple) in either species, strongly supporting the view that a suction mechanism is responsible for acquisition of milk from the nipple. Subsequent intraoral transport was different in the two species. The pigs used a second pump mechanism at the base of the tongue to transport liquid through the pillars of the fauces into the valleculae. The monkeys used a "squeeze-back" mechanism similar to the transport mechanism documented for adult macaques. Further work with other species can test our tentative hypothesis that all mammals use a negative pressure suction for acquisition, but, as is true for adult mammals, infants may use different transport mechanisms to form and move the bolus. PMID- 1629664 TI - Secondary sex characteristics and related physiological values in male fallow deer (Dama dama L.) and their relationships to changes in the annual cycle of daylengths: frequency alterations to 4- and 3-month photoperiodic cycles, and subsequent re-synchronisation under natural conditions. AB - Five adult male fallow deer were maintained in a barn with artificial light control. In a previous experiment, three 6-month photoperiodic cycles entrained morphogenetic and associated physiological values that revealed typical relationships to the antler cycle. Presented here, the light cycle was accelerated to three 4- and one 3-month photoperiods in the same group. Each artificial photoperiod generally resulted not only in an almost complete antler cycle but also in an entire cycle of seasonal fluctuations in neck girth. Increases in plasma levels of alkaline phosphatase (AP), total-, LDL- and HDL cholesterol, were generally entrained and the maxima revealed positive correlations with antler formation, but the relationships slightly diverged. In neck girth and creatinine, positive correlations to the hard antler period as well as to each other prevailed but diverged. In the 3-month photoperiodic cycle, these relationships were out of synchrony. In the second 4-month cycle, two bucks "missed" shedding and subsequent casting, but commenced antler growth in the following cycle with an in-time shedding. The possibility of desynchronisation of physiological conditions and the question of an endogenous circannual mechanism interacting with daylight are discussed. At the end of the 3-month cycle, experimental indoor and natural outdoor casting was coincident so the group was transferred to outside conditions for re-synchronisation. After spending altogether 36 months in frequency altered photoperiods, the represented values were neither synchronized nor revealed their typical relationships to the antler cycle, except of AP and neck volume. In the second cycle of re-synchronisation, all parameters, except of creatinine, appeared to be resynchronized. PMID- 1629665 TI - Expansion of surface epithelium provides the major extrinsic force for bending of the neural plate. AB - Neurulation, formation of the neural tube, requires both intrinsic forces (i.e., those generated within the neural plate) and extrinsic forces (i.e., those generated outside the neural plate in adjacent tissues), but the precise origin of these forces is unclear. In this study, we addressed the question of which tissue produces the major extrinsic force driving bending of the neural plate. We have previously shown that 1) extrinsic forces are required for bending and 2) such forces are generated lateral to the neural plate. Three tissues flank the neural plate prior to its bending: surface epithelium, mesoderm, and endoderm. In the present study, we removed two of these layers, namely, the endoderm and mesoderm, underlying and lateral to the neural plate; bending still occurred, often with complete formation of a neural tube, although the latter usually rotated toward the side of tissue depletion. These results suggest that the surface epithelium, the only tissue remaining after microsurgery, provides the major extrinsic force for bending of the neural plate and that the mesoderm (and perhaps endoderm) stabilizes the neuraxis, maintaining its proper orientation and position on the midline. PMID- 1629666 TI - Presence of a trypsin-like protease in starfish sperm acrosome. AB - Marthasterias glacialis sperm cells were treated with ionophore A23187, centrifuged, and the supernatants were assayed for esterase activity. With N benzoyl-L-arginine ethyl ester-HCl (BAEE) as substrate, a net activity was determined which was not detectable when N-acetyl-L-tyrosine ethyl ester (ATEE) was used. The BAEE trypsin-like activity was inhibited by soybean trypsin inhibitor (SBTI), N-alpha-p-tosyl-L-lysine chloromethyl ketone-HCl (TLCK), and phenyl methyl sulfonyl fluoride (PMSF), but not by L-1-tosylamido-2-phenylethyl chloromethyl ketone (TPCK). The presence of proteolytic activity in acrosomal exudates was further demonstrated by gelatin-sodium dodecyl sulfate polyacrylamide gel electrophoretic zymography (gelatin-SDS-PAGE). The presence of several bands of low proteolytic activity and of one band of high proteolytic activity, which also has the lower molecular weight, together with the fact that all are inhibited by benzamidine, suggests the existence of a trypsin-like proteinase system. The effect of the acrosomal exudate on the oocyte jelly coat was investigated by SDS-PAGE analysis. All jelly proteins appeared to be digested by the acrosomal enzymes. Furthermore, if SBTI is added shortly after insemination, the sperm fail to fertilize the oocytes. These results indicate that the starfish sperm acrosomal vesicle contains a trypsin-like protease which may be involved in sperm penetration through the oocyte jelly coat. PMID- 1629667 TI - Changes in monoamine transmitter concentration in freshwater mussel tissues. AB - Freshwater mussels were analyzed for biogenic amine transmitter substances in gill tissue, suprabranchial nerve and blood. Gill tissue from normal pondwater acclimated mussels contained significant amounts of monoamine neurotransmitter substances. In comparison with the suprabranchial nerve the gill tissue contained 42% of the dopamine, 7% of the serotonin and 490% of norepinephrine. Exposing the animals to deionized water (salt-depleted) resulted in a loss of transmitter substances from gill tissue, but serotonin reduction was modest. The mussel gill tissue content of serotonin and the precursor tryptophan was regulated at nearly constant levels. Serotonin is an important transmitter substance in mussels and the many functions it controls, including sodium transport regulation, would depend on its continued presence. PMID- 1629668 TI - Discussion of "Cerebral tissue embolization due to head trauma: a case report with immunohistochemical confirmation". PMID- 1629669 TI - Calcium alginate swabs. PMID- 1629670 TI - Polymerase chain reaction (PCR) amplification and human leukocyte antigen (HLA) DQ alpha oligonucleotide typing on biological evidence samples: casework experience. AB - The polymerase chain reaction (PCR) method of specific gene amplification was used in casework to synthesize millions of copies of the polymorphic second exon of the human leukocyte antigen (HLA)-DQ alpha (or DQA1) locus from a variety of evidence samples. The HLA-DQ alpha allelic variants in the amplified deoxyribonucleic acid (DNA) were determined in a rapid non-radioactive test by hybridization to sequence-specific oligonucleotide probes in both the dot-blot and reverse dot-blot formats. This genetic typing system has been subjected to blind proficiency testing; the performance of this test in the analysis of experimentally mixed samples was also evaluated. As of August 1990, over 250 cases have been tested and more than 2000 individual evidence (bloodstains, semen stains, individual hairs, bone fragments, and tissue sections) and reference samples have been analyzed. The first 198 of these cases are summarized in this paper; in 65% of the cases with conclusive results a suspect was included, and in 35%, all suspects were excluded. Individual cases as well as some of the general issues relating to forensic science analysis and this genetic typing system are discussed. The high rate of exclusion reported here combined with the ability of PCR to type old evidence samples suggests the relevance of this genetic test for postconviction review; two cases in which the convicted suspect was excluded are discussed. PMID- 1629671 TI - Evaluation of cast methods for estimating age from the os pubis. AB - Age-related changes of the pubic symphysis have gained wide acceptance among physical anthropologists as one basis for estimating adult skeletal age. However, these methods have not been tested by independent observers on large samples with known ages at death that represent contemporary populations. In this study 202 female and 116 male pairs of pubes collected at autopsy were blindly evaluated for age using the McKern-Stewart or Gilbert-McKern and Suchey-Brooks methods. Performance of the methods was measured by mean absolute deviation of true age from scored interval means and frequencies of true age falling within +/- 1 and +/- 2 standard deviations from the mean. The results suggest that the Suchey Brooks methods are superior in forensic applications and that the racially specific refinement for males should be used. Age estimates should include +/- 2 standard deviations, and chances of error should be considered, especially when advanced age or debilitation is suspected. PMID- 1629672 TI - Linear models for the prediction of stature from foot and boot dimensions. AB - Estimation of stature from the dimensions of foot or shoeprints has considerable forensic value in developing descriptions of suspects from evidence at the crime scene and in corroborating height estimates from witnesses. This study extends the findings of previous researchers by exploring linear models with and without gender and race indicators, and by validating the most promising models on a large, recently collected military database. Boot size and outsole dimensions are also examined as predictors of stature. The results of this study indicate that models containing both foot length and foot breadth are significantly better than those containing only foot length. Models with race/gender indicators also perform significantly better than do models without race/gender indicators. However, the difference in performance is slight, and the availability of reliable gender and race information in most forensic situations is uncertain. Analogous results were obtained for models utilizing boot size/width and outsole length/width, and in this study these variables performed nearly as well as the foot dimensions themselves. Although the adjusted R2 values for these models clearly reflect a strong relationship between foot/boot length and stature, individual 95% prediction limits for even the best models are +/- 86 mm (3.4 in.). This suggests that models estimating stature from foot/shoe-prints may be useful in the development of subject descriptions early in a case but, because of their imprecision, may not always be helpful in excluding individual suspects from consideration. PMID- 1629673 TI - A BASIC algorithm for calculating the postmortem interval from arthropod successional data. AB - A computer algorithm, implemented in the BASIC language, is presented for calculating the postmortem interval (PMI) from arthropod successional data. Entomology-assisted determination of the PMI promises to be a reliable technique in cases of homicide, suicide, accidental death, and unattended death due to natural causes. The program requires, as input, the identity of arthropod taxa recovered from human remains in a death scene investigation and machine-readable data on carrion-associated arthropod taxa and their known successional patterns of activity for the same geographical area. The program performs rapid comparisons of these lists and, on output, calculates an upper and lower estimate of the PMI, identifies the definitive taxa for these limits, and determines if the remaining corpse taxa have known successional patterns that are consistent for this estimate. An alternate output is provided if one or more corpse taxa do not overlap all the others at any single time in the succession. In that event, the user is prompted to recheck the identity of the non-overlapping taxon or taxa or reevaluate the environmental circumstances surrounding the case in question. Results of the analysis are saved to an ASCII file for output to a printer for making paper copies useful for the entomologist's Case Study Final Report. This program may make possible wider use of this technique in law enforcement and medical investigator offices that utilize both forensic entomologist expertise and IBM PCs (or compatible computers). PMID- 1629674 TI - Practical approach to investigative ethics and religious objections to the autopsy. AB - The application of investigative ethics to religious objections to the autopsy is essential for harmony in achieving the mission of medical legal death investigations. In Florida, an ethical advisory committee composed of religious, ethics, legal, and medical leaders established a unified statement for the practice of discretionary judgment and liaison with clergy. Our approach to religious objections to the autopsy as well as illustrative cases will be discussed. PMID- 1629675 TI - Dangerousness of the delusional misidentification of children. AB - Misidentification syndromes have been studied from a variety of perspectives, including phenomenological, biological, and nosological approaches. More recently, misidentification syndromes have been studied from a psychiatric-legal perspective, especially with regards to the problem of dangerousness. Capgras syndrome and other syndromes of misidentification can lead to hostile mood and subsequent physical violence. Little attention has so far been devoted to children as the objects of the psychotic person's misidentification delusion(s). We provide a review of cases from the anglophonic literature that have children as the misidentified objects, add three new cases, and then discuss the relationship between misidentification and potential harm to these children. PMID- 1629676 TI - Misidentification of self and the Riel Phenomenon. AB - Misidentification syndromes or phenomena are found in a number of psychiatric situations that may become the subject of forensic science review. One of the most curious is misidentification of self in which the individual perceives himself or herself as another being while able to explain the loss of the original identity. Recognizing these phenomena may be helpful in accurate diagnosis, in considering such conditions as psychosis of whatever type, multiple personality disorder, and other amnesia and fugue states, and in understanding the person's psychopathology. Two cases are presented to illustrate a process that the authors have named the Riel Phenomenon, after the person who was a party to what is often recognized as the most famous case in Canadian history. PMID- 1629677 TI - The trial of Louis Riel: a study in Canadian psychiatry. AB - The Riel case in 1885 is one of the most striking cases in the history of forensic psychiatry. On the one hand, Riel was the hero of the underprivileged, French Canadian-Indian halfbreeds whose futile revolt in the Canadian Northwest captured the imaginations of French Canadians in Quebec, for whom he became a hero and a martyr. Prior review in this journal has detailed the clinical data referrable to his mental condition. This paper reviews the actual trial, the questionable management by the defense, and the inadequate preparations by the defense psychiatrists. Subsequent to the sentence of death, the Canadian prime minister, Macdonald, ordered a medical review, more or less dictating the result. For whatever reason, the medical reports when made public did not fully reflect the actuality of what occurred. The result was a questionable execution, the creation of a martyr, and a spark for the cultural conflict that continues to bedevil Canada. PMID- 1629678 TI - Deoxyribonucleic acid (DNA) typing of human leukocyte antigen (HLA)-DQA1 from single hairs in Japanese. AB - The deoxyribonucleic acid (DNA) typing of human leukocyte antigen (HLA)-DQA1 from single hairs is described. HLA-DQA1 genotypes could be determined from single plucked hair roots. However, it was not easy to type HLA-DQA1 with hair shaft portions. Increase in the specimens of hair shaft portions (over 10 cm in length) to get sufficient DNA caused inhibition of polymerase chain reaction (PCR). Synthetic melanin as well as the one extracted from hairs inhibited the PCR of the genomic DNA template when added to the PCR reaction at the concentrations over than 15 ng/100 microL. Therefore, typability of hair shaft portions seems to depend on the delicate balance of the concentrations of DNA and the contaminated melanin in the final DNA extracts. PMID- 1629679 TI - Scanning electron microscopy: application in the identification of diatoms in cases of drowning. AB - A simple and rapid method is described for processing organ and water samples for the identification of diatoms so that they can be studied and recorded for taxonomic and diagnostic purposes. Samples are treated with concentrated nitric acid; the fluid obtained is centrifuged, and its sediment is dried, coated, and examined under the scanning electron microscope. The method does not alter the morphology of diatoms and allows the study of freshwater and seawater species present in the organs of bodies found in the water, making possible the diagnosis of drowning under specific conditions. PMID- 1629680 TI - Preliminary observations of the effect of methamphetamine in decomposing tissues on the development rate of Parasarcophaga ruficornis (Diptera: Sarcophagidae) and implications of this effect on the estimations of postmortem intervals. AB - Larvae of Parasarcophaga ruficornis (Fabricius) (Diptera: Sarcophagidae) were reared on tissues from rabbits administered different dosages of methamphetamine to study the effects of this drug on development of this species. The rabbits were given 37.5, 71.4, and 142.9 mg of methamphetamine via ear vein infusion. From Hours 30 to 60, larvae feeding on tissues from rabbits receiving 71.4 and 142.9 mg of methamphetamine developed more rapidly than larvae from the control colony and those feeding on tissues from the rabbit receiving 37.5 mg of methamphetamine. The time required for pupariation was significantly greater for colonies fed on tissues from methamphetamine-dosed rabbits than for the control. These differences were sufficient to alter postmortem interval estimates based on larval development by up to 18 h and estimates based on puparial development by up to 48 h. The presence of methamphetamine or amphetamine could not be detected in Diptera larvae in this experiment using radioimmunoassay techniques, as there was a nonspecific reaction, resulting in a false positive. PMID- 1629681 TI - Acallosal brain in sudden infant death syndrome (SIDS). AB - A definitive explanation of "crib" or "cot" death remains unknown. An unusual incidental autopsy finding of agenesis of the corpus callosum in a case presenting as "near miss" sudden infant death syndrome (SIDS) is discussed. Hitherto, only a single case associated with SIDS has been reported in the literature. The condition may be easily missed outside the interest in neuropathology. PMID- 1629682 TI - Estimating the prevalence of organic brain dysfunction in maximum-security forensic psychiatric patients. AB - This is a descriptive study of 50 randomly selected male patients retained in a maximum-security state hospital for mentally disordered offenders. Data regarding the prevalence of several indicators of potential organic brain dysfunction are presented, including: (1) a diagnosis of any organic brain disorder, (2) a history of severe head injury with loss of consciousness, (3) a history of seizure activity, (4) evidence of cognitive impairment, (5) abnormal neurological findings, and (6) other relevant neurodiagnostic or historical findings. Results show that multiple indicators of potential brain dysfunction were present in 64% of the cases. At least one indicator of potential brain dysfunction was present for 84% of the subjects. Subjects with a diagnosis or history suggesting brain dysfunction were significantly more likely to have been indicted for violent criminal charges (p = 0.01). Implications of these findings for clinical treatment and forensic science decision-making are discussed. PMID- 1629683 TI - New perspectives in the legal psychiatry of cocaine-related crimes. AB - The legal criteria for the insanity defense as it applies to cocaine-related crimes remains elusive because of cocaine's unique spectrum of effects on human thought and action. This paper discusses the literature relevant to cocaine and forensic psychiatry/psychology, and summarizes the results of a survey of forensic psychiatrists on the topic of drug-induced psychosis. A conceptual framework is posited for the expert witness to distinguish the separable effects of cocaine on human behavior and to clarify their relationship to criminal responsibility. PMID- 1629684 TI - Simulated paraphilias: a preliminary study of patients who imitate or exaggerate paraphilic symptoms and behaviors. AB - In a consecutive series of admissions to the Johns Hopkins Sexual Disorders Unit, 4 out of 20 patients appeared to have simulated paraphilic symptoms that further assessment indicated were either exaggerated or not present. The paper presents case histories of these 4 patients. A descriptive comparison is made between these patients and control groups of patients who admitted having paraphilic symptoms and a group of patients accused of having paraphilic symptoms but who denied them. Patients who simulated paraphilias tended to be self-referred (75%) and without current legal charges (100%). None of these patients was referred or sought treatment for pedophilia, in contrast to the other two patient groups, in which pedophilia accounted for 75% of the referrals. Several possible explanations for why patients might simulate paraphilias and implications for therapists who evaluate or treat sex offenders are discussed. PMID- 1629685 TI - Biology, violence, and antisocial personality. AB - Previous reports have examined separately the role of perinatal biology in the etiology of violent criminal behavior and the etiology of antisocial personality disorder (ASP). This paper brings together those two studies to test the hypothesis that violent behavior and ASP may result from different etiological factors. The two studies are on Danish birth cohorts, examined both for perinatal health and for violent, aggressive, and antisocial behavior later in life. Results suggest that while perinatal factors may be important in the etiology of violent criminal behavior, they do not appear to be similarly influential in the formation of ASP. These two studies are examined and their results and findings discussed in light of the limited literature in this area. PMID- 1629686 TI - Language disorders in disruptive behavior disordered homicidal youth. AB - Eight homicidal youths were assessed for language disorders and psychiatric diagnoses using a battery of standardized language tests and the Diagnostic Interview for Children and Adolescents. Both language disorders and Diagnostic and Statistical Manual III-R psychiatric diagnoses were present in all subjects. PMID- 1629687 TI - Prosecuting assaultive psychiatric patients. AB - For many reasons, inpatient psychiatric units are increasingly faced with treatment and management of violent individuals. This fosters a need to consider potential institutional responses to patient violence. This paper focuses on one response--prosecution of these persons. The existing literature on this topic is reviewed. In addition, the case history of a difficult but successful prosecution of an assaultive patient is presented. This case highlighted the development of guidelines, which are outlined herein, for determining the appropriateness of seeking legal action against patients. The paper concludes with an assessment of the benefits and risks associated with patient prosecution. PMID- 1629688 TI - Homelessness and the mentally ill offender. AB - This paper presents the results of a retrospective analysis of the discharge summaries of 69 mentally ill offenders. The subjects were patients in a New York State Psychiatric Hospital for a two-year period between January 1988 and December 1989 who were referred by the courts under New York State Criminal Procedure Law (CPL). The subjects were further compared as to homelessness at the time of the instant offense to study the association of this variable and criminal behavior among the mentally ill. Statistical analyses demonstrated significant relationships between variables of homelessness, prior offense history, and substance abuse. PMID- 1629689 TI - Assessing civil competence in the elderly. AB - This study was designed to establish reliability of the Community Competence Scale-Revised (CCS-R) and provide evidence for its validity in making discriminations relevant to civil competence in the elderly. The CCS-R is an individually administered structured interview of 17 subscales. Criterion groups were formed by drawing a sample of research participants from a retirement complex with various levels of care and with nurses having extensive knowledge of the residents' level of functioning. The study demonstrated high reliability and found converging evidence for the effectiveness of the CCS-R in making discrimination about competence in the elderly. The study had added to the growing evidence that it is possible to standardize the assessment of civil competence, thereby making the adjudication process a more accurate one. PMID- 1629690 TI - Complete sequence of maize stripe virus RNA4 and mapping of its subgenomic RNAs. AB - The complete nucleotide sequence of maize stripe virus RNA4 was determined and found to consist of 2227 nucleotides containing two significant open reading frames. One, in the 5' end of the viral RNA, encodes the major non-capsid protein of M(r) 19,815. The other is located in the 5' end of the viral complementary RNA and could encode a protein of M(r) 31,900. This protein has not been identified previously and has been designated NS4, a non-structural protein. RNA-RNA hybridization detected subgenomic RNAs encoding these proteins, a characteristic of RNA possessing an ambisense gene organization. PMID- 1629691 TI - Virus-specific proteins in cells infected with tomato black ring nepovirus: evidence for proteolytic processing in vivo. AB - The synthesis of proteins encoded by the RNA of tomato black ring virus (TBRV) in vivo was studied in protoplasts by direct labelling with [35S]methionine, and in protoplasts and plants by immunoblotting experiments with specific antisera. Comparison of the proteins synthesized in infected and mock-inoculated protoplasts suggested that proteins of M(r) 120K, 90K, 80K, 57K and 46K were virus-specific. The proteins derived from the RNA-1-encoded polyprotein detected by immunoblotting were a stable 120K protein and, only in protoplasts, small amounts of a 90K protein which contains the C-terminal part of the 120K protein and the polymerase domain. The results suggest that the polymerase and the adjacent protease function in vivo largely or solely when combined in a 120K protein. The proteins derived from the RNA-2-encoded polyprotein detected by immunoblotting were 59K and 57K proteins, which reacted with antiserum to TBRV particles, and a 46K protein. In extracts of infected Nicotiana clevelandii and Chenopodium quinoa made soon after inoculation, the 59K protein was more abundant than the 57K protein; later samples contained similar quantities of each protein. The 57K protein comigrated with protein extracted from virus particles. The results of amino acid sequencing suggested that the 57K protein is derived from the 59K protein by the loss of nine C-terminal amino acids. Antiserum to a peptide adjacent to the 57K protein in the 150K polyprotein detected a 46K protein in protoplasts and plant tissue. The results support the processing scheme for TBRV polyproteins proposed after analysis of the products of in vitro translation. PMID- 1629692 TI - Early embryo invasion as a determinant in pea of the seed transmission of pea seed-borne mosaic virus. AB - Seed transmission of an isolate of pea seed-borne mosaic virus (PSbMV) in several pea genotypes has been studied. Cross-pollination experiments showed that pollen transmission of PSbMV did not occur and accordingly, virus was not detected in pollen grains by ELISA or electron microscopy. Comparative studies between two pea cultivars, one with a high incidence of seed transmission and one with none, showed that PSbMV infected the floral tissues (sepals, petals, anther and carpel) of both cultivars, but was not detected in ovules prior to fertilization. Virus was detected equally well in seed coats of the progeny in both cultivars. Analysis of virus incidence and concentration in pea seeds of different developmental stages demonstrated that in the cultivar with a high incidence of seed transmission, PSbMV directly invaded immature embryos, multiplied in the embryonic tissues and persisted during seed maturation. In contrast, the cultivar without seed transmission did not show invasion of immature embryos by the virus; there was no evidence for virus multiplication or persistence during embryo development and seed maturation. Hence seed transmission of PSbMV resulted from direct invasion of immature pea embryos by the virus and the block to seed transmission in the non-permissive cultivar probably occurred at this step. PMID- 1629693 TI - Physical map of the Cryptophlebia leucotreta granulosis virus genome and its relationship to the genome of Cydia pomonella granulosis virus. AB - A physical map of the genome of Cryptophlebia leucotreta granulosis virus (CIGV) was constructed for the restriction enzymes BamHI, EcoRI, KpnI, NdeI, NruI, SacI and XhoI using hybridization techniques. The size of the viral genome was determined to be 112.4 kbp. A restriction fragment library covering almost the entire genome of CIGV was constructed, and the position of the granulin gene was identified by cross-hybridization with granulin coding fragments of Cydia pomonella granulosis virus (CpGV). Two further regions of intergenomic similarity between CIGV and CpGV were mapped. These regions were aligned and show a collinear arrangement. PMID- 1629694 TI - Persistence and expression of Microplitis demolitor polydnavirus in Pseudoplusia includens. AB - Persistence and expression of Microplitis demolitor polydnavirus (MdPDV) was examined in parasitized and virus-injected Pseudoplusia includens larvae. Viral DNA persisted in P. includens larvae for 6 days, but no increase in the amount of viral DNA present was detected. Viral transcripts were observed in parasitized and virus-injected larvae 4 h post-parasitism and expression continued for 6 days. When specific host tissues were examined, more viral DNA and RNA was detected in haemocytes than in the gut, nervous system and fat body. 32P-labelled MdPDV DNA hybridized to approximately six different size classes of mRNAs on Northern blots of RNA from haemocytes of parasitized larvae. MdPDV transcription was first detected in haemocytes at 4 h post-parasitism and continued for 6 days. Similar transcripts were observed in haemocytes from larvae that had been injected with calyx fluid or MdPDV plus venom. First-strand cDNA probes of haemocyte-specific MdPDV transcripts hybridized to only certain MdPDV viral DNAs, suggesting that only part of the MdPDV genome is expressed in this host cell type. PMID- 1629695 TI - Scrapie in the central nervous system: neuroanatomical spread of infection and Sinc control of pathogenesis. AB - Following bilateral intraocular (i.o.) infection of Sinc s7 mice with ME7 scrapie, sequential tissue pools were taken from retina, optic nerve, superior colliculus (SC), dorsal lateral geniculate nucleus (dLGN), visual cortex and cerebellum. The infectivity levels in these pools were estimated by intracerebral (i.c.) assay in C57BL/FaBtDk mice. Infectivity was first detected in retina at 35 days post-injection (as an increase above residual injected inoculum), SC at 56 days, dLGN at 77 days and in optic nerve, visual cortex and cerebellum at 98 days. Pathological lesions were shown to develop in the same sequence later in the incubation period. Comparison of sequential retina and SC assays in congenic mice, which differ only in the vicinity of the Sinc locus, revealed a difference in the initial detection and progression of i.o. infection of between 60 and 100 days, indicating that Sinc acts by delaying the initiation of replication. Higher levels of infectivity were found in retina and SC of mice infected with 79A scrapie, which destroys the photoreceptor layer in the retina, than with ME7 scrapie, which does not. Retrograde transport of infection was indicated by the levels of infectivity in the retina after i.c. infection with ME7 or 79A scrapie. These results indicate that scrapie spread within the central nervous system is restricted to neuroanatomical pathways, and that Sinc controls the initiation, but not the rate of replication. PMID- 1629696 TI - A leucine zipper structure present in the measles virus fusion protein is not required for its tetramerization but is essential for fusion. AB - The biological role of a leucine zipper motif present in the measles virus fusion (F) protein has been investigated. This motif is present in all paramyxovirus F proteins, all coronavirus spike proteins and many if not all retrovirus envelope proteins. By analogy to its role in certain transcription factors, it has been suggested that the motif may be responsible for the oligomerization of these viral membrane proteins. In this study, one, two or four heptadic leucines in the motif were substituted using site-directed mutagenesis. We found that fusion is prevented when all four heptadic leucines present in the motif are mutated whereas cellular transport and the oligomeric state of the F protein are unaffected. PMID- 1629697 TI - Sequence analysis of the 22K, SH and G genes of turkey rhinotracheitis virus and their intergenic regions reveals a gene order different from that of other pneumoviruses. AB - The nucleotide and deduced amino acid sequences of three genes of turkey rhinotracheitis virus (TRTV) together with the nucleotide sequences of the relevant intergenic regions were determined. The deduced amino acid sequence of one of the genes shows significant identity (42%) to that of the 22K protein of human respiratory syncytial virus (RSV). The TRTV 22K gene, like that of RSV, has a second open reading frame, although the amino acid sequence deduced from this reading frame does not show any similarity to the equivalent predicted RSV protein. The other two genes and their deduced amino acid sequences do not show any sequence similarity to the genes of other pneumoviruses. However, the hydrophobicity profiles of the predicted proteins do show similarities to those of the small hydrophobic (SH) and attachment protein (G) genes of RSV. The TRTV G gene is 1193 nucleotides in length and encodes a protein of 391 amino acids (M(r) 42984), which is rather larger than the RSV G protein (predicted M(r) 36000). The TRTV SH gene is 589 nucleotides in length, encoding a protein of 174 amino acids (M(r) 18797), which is considerably larger than the size of the RSV SH protein (M(r) 7500). The sequences of the intergenic regions derived from clones of polycistronic mRNAs and polymerase chain reaction products obtained with primers from different genes reveal the order on the virus genome to be 3' F-22K-SH-G 5'. This differs from the gene order of paramyxoviruses and morbilliviruses, which lack a 22K gene (and in some cases a SH gene), and the pneumoviruses RSV and pneumonia virus of mice, which have the F and 22K genes located after the G gene. PMID- 1629698 TI - Sequence analysis of the gene encoding the fusion glycoprotein of pneumonia virus of mice suggests possible conserved secondary structure elements in paramyxovirus fusion glycoproteins. AB - The gene encoding the fusion (F) glycoprotein of pneumonia virus of mice consists of 1657 bases and contains an open reading frame encoding 537 amino acids which is more similar to the F proteins of pneumoviruses than to those of other paramyxoviruses. Computer-assisted sequence analyses can be combined with data on the antigenicity of various F proteins to suggest a possible arrangement of secondary structure elements common to all pneumovirus and paramyxovirus F proteins. PMID- 1629699 TI - Nucleotide sequence and coding strategy of the Uukuniemi virus L RNA segment. AB - The complete nucleotide sequence of the L RNA segment of Uukuniemi virus has been determined from cloned cDNA. The L RNA is 6423 nucleotides in length, and is of negative polarity. The viral-complementary RNA contains a single large open reading frame of 2104 codons which corresponds to the L protein (M(r) 241039). Comparison with the L protein sequences of other members of the Bunyaviridae showed homology with the Rift Valley fever phlebovirus L protein (38% amino acid identity), but no detectable similarity with bunyavirus, hantavirus or tospovirus L proteins. These data lend further support for the recent reclassification of uukuviruses and phleboviruses into the same genus, Phlebovirus, in the family Bunyaviridae. The L RNA sequence completes the determination of the Uukuniemi virus genome: since the M RNA segment is 3229 and the S RNA segment 1720 nucleotides, the whole genome comprises 11372 nucleotides. PMID- 1629700 TI - Activation of integrated human immunodeficiency virus type 1 in human neuroblastoma cells by the cytokines tumour necrosis factor alpha and interleukin 6. AB - Human immunodeficiency virus type 1 (HIV-1) infection was studied in two different human neuroblastoma cell lines, SK-N-MC and SH-SY5Y. Results from immunofluorescence analysis indicate that SK-N-MC cells express a 68K neurofilament, and SH-SY5Y cells express additionally a 160K to 200K neurofilament complex and thus represent a more differentiated state. HIV-1 infection in these cell lines was demonstrated by nested polymerase chain reaction and further characterized by in situ hybridization, which showed that about 50% of SK-N-MC cells and 20% of SH-SY5Y cells were infected by HIV-1 and contained integrated proviral HIV-1 DNA. Among the cytokines and growth factors studied, tumour necrosis factor alpha (TNF-alpha) enhanced virus production in both cell lines, but to a differing extent, according to our mRNA and p24 antigen capture assay. In SK-N-MC cells the enhancement of HIV-1 mRNA was detected after 24 h of stimulation, and declined to the control level by 48 h. In SH-SY5Y cells a clear-cut stimulation was seen at both time points. By contrast, interleukin-6 (IL-6) enhanced the virus replication only in SK-N-MC cells, as shown at the mRNA level. Immunochemical staining showed no differences in the proportion of HIV-1 positive cells after 48 h of stimulation by TNF-alpha or IL-6 when compared to the control cells. In addition, based on a thymidine incorporation assay, TNF alpha inhibited, but IL-6 strongly increased, the DNA synthesis in SK-N-MC cells, whereas in the SH-SY5Y cell line no such differences were seen. We discuss the possibility that developing, less-differentiated neurons may be more readily infected by HIV-1 than fully differentiated neurons, and that cytokines such as TNF-alpha and IL-6, which are elevated in HIV-1-infected individuals, may enhance HIV production. PMID- 1629701 TI - Human immunodeficiency virus type 1 (HIV-1) superinfection of a cell clone converting it from production of defective to infectious HIV-1 is mediated predominantly by CD4 regions other than the major binding site for HIV-1 glycoproteins. AB - A cell clone, L-2, which produces non-infectious doughnut-shaped human immunodeficiency virus type 1 (HIV-1) particles, was permissive for HIV-1 superinfection, which resulted in the production of infectious particles. The superinfection showed slow kinetics compared with primary HIV-1 infection of M10 cells, the parent of the L-2 cell clone. Inhibition studies on the superinfection of L-2 cells using several CD4-related reagents showed that the CD4 molecule was an essential component of the receptor for superinfection. Strong inhibitory effects were obtained using CD4 peptides such as CD4(68-130), which includes a portion homologous to the immunoglobulin third complementarity-determining region (CDR3), as well as recombinant soluble CD4. In contrast, a CD4(45-60) peptide, which includes most of the CDR2-related region, was not effective, although the Leu-3a monoclonal antibody (MAb), which recognizes a site near the CDR2-related region, did slightly, but significantly, delay the superinfection kinetics. Comparative flow cytometry of L-2 and M10 cells revealed that the cell surface of L-2 cells despite expressing HIV-1 env protein, reacted slightly with OKT4 or anti-CD4(68-130) MAb, but not with Leu-3a or OKT4A MAb. In contrast, no reaction was detected with any of these anti-CD4 MAbs on the surface of another HIV-1 superinfection-resistant cell clone, MOLT-#8IIIB-14, which expresses HIV-1 env proteins but does not produce infectious HIV-1 particles. These results strongly suggest that expression of the CD4 major receptor site for primary HIV-1 infection is preferentially decreased on the surface of L-2 cells, but that the OKT4 epitope and the nearby region corresponding to immunoglobulin CDR3 remain exposed on the cell surface. Consequently, the CD4 CDR3-related region could play a major role as the receptor for the superinfection reported here. PMID- 1629702 TI - Functional mapping of the rev-responsive element of human immunodeficiency virus type 2 (HIV-2): influence of HIV-2 envelope-encoding sequences on HIV-1 gp120 expression in the presence or absence of Rev. AB - The human immunodeficiency virus type 1 (HIV-1) regulatory protein Rev stimulates expression of structural viral proteins via a target response element (RRE) located within gag-pol and env mRNAs. To analyse the HIV-2 Rev trans-activation effect on the expression of the envelope protein, we cloned a functionally active HIV-2 rev cDNA and showed that it contained four exons. Using transient expression assays, we mapped a 353 bp RRE fragment within the env gene of HIV-2 on which both HIV-1 and HIV-2 Rev could act. Interestingly, smaller fragments suppressed the use of additional splice sites within the env gene and caused envelope protein expression independent of Rev. PMID- 1629703 TI - Failure to isolate human T cell lymphotropic virus type I and to detect variant specific genomic sequences by polymerase chain reaction in Melanesians with indeterminate western immunoblot. AB - The controversy over the endemicity of human T cell lymphotropic virus type I (HTLV-I) in Melanesia has been settled recently by the isolation of genetically distinct, highly divergent sequence variants of HTLV-I from unrelated inhabitants of Papua New Guinea and the Solomon Islands. Still at issue, however, is the significance of the high frequency of indeterminate HTLV-I Western blots (defined as reactivity to only gag-encoded proteins) among Melanesians. To investigate whether this indeterminate seroreactivity reflects specific reactivity to the Melanesian HTLV-I variants, 27 seroindeterminate Melanesians from Papua New Guinea and the Solomon Islands were studied for evidence of HTLV-I infection. Although antibodies against Melanesian variant-specific env gene products and variant-specific env gene sequences were detected by Western blot analysis and polymerase chain reaction, respectively, in all 11 HTLV-I Western blot-positive Melanesians, none of the 27 seroindeterminate Melanesians had such variant specific antibodies or HTLV-I proviral sequences. In addition, attempts to isolate HTLV-I from seroindeterminate individuals were unsuccessful. These data indicate that HTLV-I infection is not the cause of the indeterminate Western blot reactivity seen in Melanesia. PMID- 1629704 TI - Identification of two novel human immunodeficiency virus type 1 splice acceptor sites in infected T cell lines. AB - The regulatory and accessory proteins of human immunodeficiency virus type 1 (HIV 1) are produced from singly or multiply spliced mRNAs. We have used HIV-1 specific oligonucleotide primer pairs in a polymerase chain reaction procedure on RNA from lymphocyte cell lines infected with HIV-1(228,200). The amplified products were analysed by hybridization with splice junction-specific oligonucleotide probes to determine splice donor/splice acceptor combination utilization, subcloned into a plasmid vector and the nucleotide sequences were obtained. Two novel splice acceptor sites have been identified. PMID- 1629705 TI - In vitro reconstitution of active influenza virus ribonucleoprotein complexes using viral proteins purified from infected cells. AB - A procedure to obtain RNA-free preparations containing the nucleoprotein (NP) and polymerase (P) proteins from influenza virus-infected cell extracts has been developed. The influenza virus P proteins present in these preparations copied small synthetic RNA molecules derived from plasmid sequences. In addition, RNA molecules encapsidated with the NP and P proteins were amplified and packaged into virus particles when transfected into influenza virus-infected cells. Thus, the preparations of NP and P proteins display features similar to those isolated from purified influenza virions, and represent an alternative for the preparation of active influenza virus P protein. PMID- 1629706 TI - The role of CD8+T cells in the acute and chronic phases of Theiler's murine encephalomyelitis virus-induced disease in mice. AB - The technique of in vivo depletion with T cell subset-specific monoclonal antibodies was used to study the involvement of CD8+T cells in protection/pathogenesis during the acute and chronic demyelinating phases of Theiler's murine encephalomyelitis virus (TMEV)-induced disease. Mice rendered CD8-deficient prior to infection with TMEV were less efficient at clearing virus from the central nervous system compared to intact animals and also suffered demyelinating disease of earlier onset and increased severity. This indicates that CD8+ cells have a protective role in virus clearance at early times post infection, and may also be involved in downregulating the severity of the chronic demyelinating disease. How CD8+ T cells function to produce these effects is discussed. PMID- 1629707 TI - Foreign gene expression by a baculovirus vector with an expanded host range. AB - A nuclear polyhedrosis virus (NPV) (Baculoviridae)-based gene expression system was improved by DNA recombination. The BmN cell line established from Bombyx mori and the Sf21 cell line established from Spodoptera frugiperda are non-permissive for Autographa californica multicapsid NPV (AcMNPV) and B. mori NPV (BmNPV) replication, respectively. After cotransfection of AcMNPV DNA and BamHI-digested BmNPV DNA into Sf21 cells, progeny viruses were isolated by plaque purification on BmN cell monolayers and the host specificity of one viral isolate was analysed. The virus had a wider host range, and replicated and produced polyhedra in Sf21 cells, BmN cells and larvae of the silkworm, B. mori. DNA restriction endonuclease analysis showed that the isolate was a hybrid of AcMNPV and BmNPV. Using the AcMNPV transfer vector pAcYM1 a portion of the polyhedrin gene of the hybrid virus was replaced with the coding region of the firefly luciferase gene, producing a recombinant virus. The latter expressed firefly luciferase in both cell lines and in silkworm larvae under the control of the polyhedrin promoter. PMID- 1629708 TI - Characterization of two variants of Panolis flammea multiple nucleocapsid nuclear polyhedrosis virus. AB - The baculovirus Panolis flammea multiple nucleocapsid nuclear polyhedrosis virus (PfMNPV) was originally isolated from a natural virus epizootic and shown to consist of a mixture of variants. Two subclasses of variants (PfMNPV A and B) were identified by Southern blot hybridization, their polyhedrin genes being located on different restriction fragments. The proportion of the A and B variants changed according to the larval host in which the virus was propagated; PfMNPV(B) predominated in P. flammea but PfMNPV(A) was predominant in Mamestra brassicae. Bioassays of the two pure virus variants in M. brassicae larvae have shown the LD50 values to be 4610 polyhedron inclusion bodies (pibs) for PfMNPV(A) and 5937 pibs for PfMNPV(B). Genomic DNA from the two variants was compared using restriction endonuclease analysis, and dot blot and Southern blot hybridization. Reciprocal quantitative dot blot hybridization analysis in 50% formamide showed PfMNPV(A) and PfMNPV(B) to be only distantly related to Autographa californica MNPV (less than 1%) and more closely related to M. brassicae MNPV (21 to 26%). The two PfMNPV variants exhibited a very high degree of identity to each other (nearly 100%) and therefore are very closely related. This was confirmed by physical mapping of the virus genomes. The nucleotide sequence of the polyhedrin gene of PfMNPV(B) was determined and compared with the published DNA sequences of other polyhedrin genes. PMID- 1629709 TI - Partial nucleotide sequence of poplar mosaic virus RNA confirms its classification as a carlavirus. AB - The nucleotide sequence of the 3'-proximal 1328 nucleotides of poplar mosaic virus (PMV) was determined and shown to contain two large open reading frames (ORFs). The ORF nearer to the 3' terminus of the RNA is capable of encoding a polypeptide of 14K with a 'zinc-finger' motif, and is homologous to sequences in corresponding positions in five other carlaviruses. The other ORF encodes a protein of 36K which includes two sequences of amino acids identified in tryptic digests as virion capsid protein, and has amino acid sequences in common with both carlaviruses and potexviruses. PMID- 1629710 TI - Receptor for pre-S1(21-47) component of hepatitis B virus on the liver cell: role in virus cell interaction. AB - Attachment of hepatitis B virus to a hepatoblastoma cell line (HepG2) was examined using a synthetic peptide corresponding to the pre-S1 (21-47) region of the envelope protein. Scatchard analysis revealed a single class binding site of Kd 104 +/- 27 nM/l and 5.4 +/- 1.2 x 10(5) sites per cell. Competition of HBV with pre-S1 peptides was dose dependent, and demonstrated it as the dominant binding site. In view of the suggested sequence homology between the peptide and IgA, cross-competition studies were carried out. The results indicate no direct role of IgA receptor in HBV binding. The receptor for the pre-S1 peptide was identified as a single major peptide of molecular weight 31 kD using in-situ ligand receptor crosslinking. PMID- 1629711 TI - Effects of 2'-fluorinated arabinosyl-pyrimidine nucleosides on duck hepatitis B virus DNA level in serum and liver of chronically infected ducks. AB - The 2'-fluorinated arabinosyl-pyrimidine nucleosides, 1-(2'-deoxy-2'-fluoro-beta D-arabinofuranosyl)-5-iodocytosine (FIAC) and 1-(2'-deoxy-2'-fluoro-beta-D arabinofuranosyl)-5-methyluracil (FMAU), are new antiviral compounds with in vitro inhibitory activity against the DNA polymerase of hepadnaviruses. Those compounds also induced permanent inhibition of viral replication in woodchucks chronically infected by woodchuck hepatitis virus. The effects of these antiviral compounds were assessed in ducks chronically infected by duck hepatitis B virus (DHBV). Following intraperitoneal administration for 5 days, FMAU (2 mg/kg/day) and FIAC (10 mg/kg/day) induced a transient decrease in DHBV replication, as shown by the decrease in both the serum and liver DHBV DNA level. After stopping therapy, DHBV replication rebounded immediately to the pretreatment level. The supercoiled form of liver viral DNA was found to be less affected by the therapy. By contrast, no obvious antiviral effect was observed with vidarabine monophosphate (ara-AMP) (80 mg/kg/day) therapy. No sign of toxicity was observed during the course of the treatment. These preliminary results confirmed in the DHBV model the higher efficacy of FIAC and FMAU as compared to ara-AMP. Pharmacokinetic studies are needed to explain the differences observed in viral replication in these 2 models of HBV infection. PMID- 1629712 TI - Inhibition of HIV-1 infection in vitro by murine monoclonal anti-p24 antibodies. AB - Murine monoclonal antibodies (Mabs) to the major core protein p24 of the human immunodeficiency virus type 1 (HIV-1) were tested for their ability to inhibit the replication and spread of the virus in permanent cell cultures (Molt4/8, K37, H9) and in the culture of II-2 stimulated T cells of healthy donors. After addition of ascitic fluid containing monoclonal anti-p24 antibodies or purified anti-p24 antibodies or the respective control to co-cultures of infected and non infected cells, HIV-1 replication was evaluated by determining the percentage of infected cells and the activity of reverse transcriptase (RT) in cell-free supernatant. In addition, the supernatant's infectivity was determined. FACS analysis demonstrated p24 antigen in about 40% of unfixed HIV-1 infected cells at the cell membrane. Monoclonal anti-p24 antibodies of different epitope specificity added to the cells but not to the virus delayed the spread of HIV-1 infection in permanent cell culture. Furthermore, anti-p24 Mabs inhibited the release of RT-active virus particles by HIV-1 infected cell lines or II-2 stimulated T-lymphocytes, respectively, up to 60%. The mode of action of anti-p24 antibodies after HIV-1 infection is discussed on the basis of the data obtained. PMID- 1629713 TI - Detection of adenoviruses in stools from healthy persons and patients with diarrhea by two-step polymerase chain reaction. AB - The use of the polymerase chain reaction (PCR) for detection of human adenoviruses in diluted stool samples was investigated. Two sets of nested primers, including primers specific for the hexon-coding region and for the E1B region of enteric adenoviruses (EAd), were assessed by two-step amplification. The primers constitute two different PCR systems designed for the detection of adenoviruses belonging to all six subgenera (A-F), and the two EAds Ad40 and Ad41, respectively. In a two-step PCR mediated amplification a single virus particle was detected when the two sets of general hexon primers or EAd specific primers were used. Earlier results from PCR detection of adenoviruses in stool from children suffering from diarrhea gave indications that adenovirus particles are commonly shed in stools without being identified as the cause of illness [Allard et al.: Journal of Clinical Microbiology 28:2659-2667, 1990]. Therefore, the general and the EAd specific PCR assays were assessed on 150 stool specimens from three groups including 50 healthy children, 50 healthy adults, and 50 adults suffering from diarrhea. When the two sets of general hexon primers were used, 25 of the 50 specimens from the healthy children (mean age 21 months) were found positive by two-step PCR amplification. Nine of the 50 specimens from the healthy adults (mean age 32 years) were found positive whereas 12 of the 50 specimens from sick adults (mean age 31 years) gave amplification products, using the two sets of general hexon primers in a nested fashion. None of the 150 specimens were found to be positive by two-step PCR amplification using the two sets of EAd specific primers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629714 TI - Infection with hepatitis A, B, delta, and human immunodeficiency viruses in children receiving cycled cancer chemotherapy. AB - Serological markers of hepatitis A, B, and Delta and human immunodeficiency viruses were studied in 25 children receiving cancer chemotherapy. Eighty-eight percent had pre-existing HAV immunity which was unaltered by chemotherapy. HDV infection was observed in 8% while HIV was conspicuous by its absence. Active HBV infection, observed in 76% of the children, was asymptomatic in the majority and was accompanied by a high incidence of HBe antigenaemia (57.9%) and its persistence. Pre-existing anti-HBs failed to prevent HBV infection recurrence, which was, however, transient and self-limiting. Multiple blood transfusions and repeated parenteral exposures appeared to be the possible sources of HBV acquisition. Transmission to close contacts was also observed. The study suggests that although HBV vaccine might not be protective against HBV infection in patients receiving cancer chemotherapy, it may prevent its persistence and thereby help in reducing chronic liver disease-related morbidity and a highly infectious reservoir. Strict HBV screening of blood donors, exclusive use of disposable equipment, and vaccination of close contacts of cancer patients is recommended, particularly in HBV endemic third-world countries. PMID- 1629715 TI - N-methylation of dopamine-derived 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, (R)-salsolinol, in rat brains: in vivo microdialysis study. AB - N-Methylation of (R)-1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [(R) salsolinol] derived from dopamine was proved by in vivo microdialysis study in the rat brain. The striatum was perfused with (R)-salsolinol and N-methylated compound was identified in the dialysate using HPLC and electrochemical detection with multichanneled electrodes. N-Methylation of (R)-salsolinol was confirmed in three other regions of the brain, the substantia nigra, hypothalamus, and hippocampus. In the substantia nigra, the amount of N-methylated (R)-salsolinol was significantly larger than in the other three regions. These results indicate that around dopaminergic neurons, particularly in the substantia nigra, (R) salsolinol was methylated into N-methyl-(R)-salsolinol, which has a chemical structure similar to that of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, the selective dopaminergic neurotoxin. N-Methylation of tetrahydroisoquinolines and beta-carbolines have already been proven to increase their toxicity to dopaminergic neurons and N-methylation might be an essential step for these alkaloids to increase their toxicity. On the other hand, after perfusion of (R) salsolinol, release of dopamine and 5-hydroxytryptamine was observed and inhibition of monoamine oxidase was indicated. (R)-Salsolinol and its derivatives may be candidates for being dopaminergic neurotoxins. PMID- 1629716 TI - Amitriptyline prevents N-methyl-D-aspartate (NMDA)-induced toxicity, does not prevent NMDA-induced elevations of extracellular glutamate, but augments kainate induced elevations of glutamate. AB - The effect of amitriptyline on kainate- and N-methyl-D-aspartate (NMDA)-induced toxicity and release of amino acids from cerebellar granule neurons was studied. The ED50 for amitriptyline, imipramine, and nortriptyline protection against NMDA induced toxicity was 6.9, 6.5, and 1.3 microM, respectively. None of these compounds protected against kainate-induced toxicity. Even though amitriptyline was protective against NMDA-induced toxicity, it had no effect on the NMDA induced increase in extracellular levels of glutamate or aspartate from these cells, indicating a dissociation between NMDA receptor activation (as indicated by glutamate content elevations) and NMDA-induced toxicity. However, kainate and quisqualate treatment resulted in elevations of glutamate and taurine levels that were further augmented in the presence of 25 microM amitriptyline. These findings confirm the reports of others that tricyclic antidepressants have neuroprotective effects related to the NMDA receptor and expand on these reports by showing that even though there is protection against toxicity, the NMDA receptor is nevertheless activated, suggesting an involvement of these compounds at sites removed from the receptor. Furthermore, this is the first report showing an interaction of tricyclic antidepressants with the function of non-NMDA receptors. PMID- 1629717 TI - Differential effects of insulin on choline acetyltransferase and glutamic acid decarboxylase activities in neuron-rich striatal cultures. AB - We studied the effects of insulin, nerve growth factor (NGF), and tetrodotoxin (TTX) on cellular metabolism and the activity of glutamic acid decarboxylase (GAD) and choline acetyltransferase (ChAT) in neuron-rich cultures prepared from embryonic day 15 rat striatum. Insulin (5 micrograms/ml) increased glucose utilization, protein synthesis, and GAD activity in cultures plated over a range of cell densities (2,800-8,400 cells/mm2). TTX reduced GAD activity; NGF had no effect on GAD activity. Insulin treatment reversibly reduced ChAT activity in cultures plated at densities of greater than 4,000 cells/mm2, and the extent of this reduction increased with increasing cell density. The number of acetylcholinesterase-positive neurons was not reduced by insulin, suggesting that insulin acts by down-regulating ChAT rather than by killing cholinergic neurons. Insulin-like growth factor-1 (IGF-1) reduced ChAT activity at concentrations 10 fold lower than insulin, suggesting that insulin's effect on ChAT may involve the IGF-1 receptor. NGF increased ChAT activity; TTX had no effect on ChAT activity. These results suggest that striatal cholinergic and GABAergic neurons are subject to differential trophic control. PMID- 1629718 TI - The adenosine receptors present on the plasma membrane of chromaffin cells are of the A2b subtype. AB - The adenosine receptors in the plasma membrane of chromaffin cells from bovine adrenal medulla were characterized. The presence of A1 receptors was discounted owing to the absence of R-[3H]phenylisopropyladenosine (R-PIA) and [3H]8 cyclopentyl-1,3-dipropylxanthine ([3H]-DPCPX) binding. The binding of the specific A2a ligand CGS-21680 was low. In contrast, the binding of 5'-(N-[3H] ethylcarboxamidoadenosine ([3H]NECA) was relatively high (1.7 pmol/mg of protein at a ligand concentration up to 90 nM). This binding did not correspond to non adenosine receptor NECA binding sites because the specific [3H]-NECA binding was similar when unlabeled adenosine, NECA, or R-PIA was used to measure the nonspecific binding. The rank order of potency of different ligands for the displacement of specific [3H]NECA binding was DPCPX greater than NECA greater than chloroadenosine greater than R-PIA greater than theophylline = CGS-21680. These results indicate that the receptors present on the plasma membrane of chromaffin cells are exclusively of the A2b subtype. PMID- 1629719 TI - Brain-derived neurotrophic factor is more highly conserved in structure and function than nerve growth factor during vertebrate evolution. AB - Mammalian nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are members of a protein family with perfectly conserved domains arranged around the cysteine residues thought to stabilize an invariant three-dimensional scaffold in addition to distinct sequence motifs that convey different neuronal functions. To study their structural and functional conservation during evolution, we have compared NGF and BDNF from a lower vertebrate, the teleost fish Xiphophorus, with the mammalian homologues. Genomic clones encoding fish NGF and BDNF were isolated by cross-hybridization using probes from the cloned mammalian factors. Fish NGF and BDNF were expressed by means of recombinant vaccinia viruses, purified, and their neuronal survival specificities for different classes of neurons were found to mirror those of the mammalian factors. The half-maximal survival concentration for chick sensory neurons was 60 pg/ml for both fish and mammalian purified recombinant BDNF. However, the activity of recombinant fish NGF on both chick sensory and sympathetic neurons was 6 ng/ml, 75-fold lower than that of mouse NGF. The different functional conservation of NGF and BDNF is also reflected in their structures. The DNA-deduced amino acid sequences of processed mature fish NGF and BDNF showed, compared to mouse, 63% and 90% identity, respectively, indicating that NGF had reached an optimized structure later than BDNF. The retrograde extrapolation of these data indicates that NGF and BDNF evolved at strikingly different rates from a common ancestral gene about 600 million years ago. By RNA gel blot analysis NGF mRNA was detected during late embryonic development; BDNF was present in adult brain. PMID- 1629720 TI - Effects of muscarinic agonists and depolarizing agents on inositol monophosphate accumulation in the rabbit vagus nerve. AB - The effects of muscarinic agonists and depolarizing agents on inositol phospholipid hydrolysis in the rabbit vagus nerve were assessed by the measurement of [3H]inositol monophosphate production in nerves that had been preincubated with [3H]inositol. After 1 h of drug action, carbachol, oxotremorine, and arecoline increased the inositol monophosphate accumulation, though the maximal increase induced by these agonists differed. Addition of the muscarinic antagonists atropine or pirenzepine shifted the carbachol dose response curves to the right, without decreasing the carbachol maximal stimulatory effects. The KB for pirenzepine was 35 nM, which is characteristic of muscarinic high-affinity binding sites coupled to phosphoinositide turnover and often associated with the M1 receptor subtype. On the other hand, agents known to depolarize or to increase the intracellular Ca2+ concentration, e.g., elevated extracellular K+, ouabain, Ca2+, and the Ca2+ ionophore A23187, also increased inositol monophosphate accumulation. These effects were not mediated by the release of acetylcholine, as suggested by the fact that they could not be potentiated by the addition of physostigmine nor inhibited by the addition of atropine. The Ca(2+)-channel antagonist Cd2+, also known to inhibit the Na+/Ca2+ exchanger, was able to block the effects of K+ and ouabain, but did not alter those of carbachol. These results suggest that depolarizing agents increase inositol monophosphate accumulation in part through elevation of the intracellular Ca2+ concentration and that muscarinic receptors coupled to phosphoinositide turnover are present along the trunk of the rabbit vagus nerve. PMID- 1629721 TI - Enhancement of endogenous release of glutamate and gamma-aminobutyric acid from hippocampus CA1 slices after in vivo long-term potentiation. AB - The effect of long-term potentiation (LTP) on endogenous amino acid release from rat hippocampus slices was studied. LTP was induced in vivo by application of a tetanus (200 Hz, 200 ms) to the Schaffer collateral fibers in unanesthetized rats. Endogenous release of glutamate and gamma-aminobutyric acid (GABA) was investigated 60 min after tetanization in CA1 subslices of potentiated and control rats. No significant effects of LTP were observed in basal and K(+) induced Ca(2+)-independent release components of these amino acids. In contrast, K(+)-induced Ca(2+)-dependent release of both glutamate and GABA increased approximately 100% in slices from potentiated rats. No differences were observed in total content of glutamate and GABA between the subslices from control and LTP animals. These results suggest a persistent increase in the recruitment of the presynaptic vesicular pool of glutamate and GABA during LTP. PMID- 1629722 TI - Lipid composition in synaptic and nonsynaptic mitochondria from rat brains and effect of aging. AB - The cholesterol, phospholipid, and fatty acid compositions in synaptic and nonsynaptic mitochondria from rat brains and the effect of aging were studied. Both cholesterol and phospholipid contents were found to be significantly different in synaptic compared to nonsynaptic mitochondria. In both types of brain mitochondria, aging decreases the cholesterol content by 27% and the phospholipid content by approximately 12%. The difference between these decreases observed in the organelles causes decreases in the cholesterol/phospholipid molar ratios for synaptic and nonsynaptic mitochondria of 17 and 19%, respectively. Also, the phospholipid composition is significantly different in synaptic compared to nonsynaptic mitochondria. Among phospholipids, only the cardiolipin fraction showed a significant decrease (26%) in nonsynaptic mitochondria from the brains of aged rats. Instead, the fatty acid composition was not significantly different in synaptic compared to nonsynaptic mitochondria. The 21% aging decrease in linoleic acid (18:2), observed only in nonsynaptic mitochondria, may be related to a decrease in cardiolipin, which contains a large amount of this fatty acid. PMID- 1629723 TI - Mono-N-methylation of 1,2,3,4-tetrahydro-beta-carbolines in brain cytosol: absence of indole methylation. AB - In an accompanying report we demonstrated enzyme activity in guinea pig brain cell nuclei that catalyzes S-adenosylmethionine (SAM)-dependent N-methylations of heteroaromatic beta-carbolines (BCs) on the 2[beta]-nitrogen and subsequently on the 9[indole]-nitrogen, ultimately yielding N2,N9-dimethylated BCs. Presented here are the results of a parallel study of the N-methylation of 1,2,3,4 tetrahydro-BCs (THBCs), which form endogenously via condensations of tryptophan and its derived indoles with carbonyl compounds or, like their BC oxidation products, are environmental constituents and plant alkaloids. THBCs were enzymatically methylated on the 2[beta]-nitrogen by [3H]-SAM in undialyzed homogenates of rat or guinea pig brain, but [3H]methyl transfer to the 9[indole] nitrogen was not observed. The structure of the 2[beta]-methyl THBC product was verified with capillary gas chromatography-mass spectrometry. Furthermore, whereas BC N-methylation was largely particulate and displayed micromolar Km values for BC substrate, THBC 2[beta]-N-methylation activity was cytosolic and displayed a relatively high (millimolar) Km for THBC substrate. The N-methylation of THBCs may be due to cytosolic N-methyltransferases that others have studied using different azaheterocyclics. Our overall studies indicate that N2,N9 dimethylated BCs could be unique neurotoxic factors that are bioactivated within brain by sequential N-methylations of BCs. These results suggest the possibility of an additional route to the putative 2,9-dimethylated toxins involving, as a first step, 2[beta]-N-methylation of environmental or endogenously derived THBCs in the brain and perhaps other organs. PMID- 1629724 TI - Novel S-adenosylmethionine-dependent indole-N-methylation of beta-carbolines in brain particulate fractions. AB - Guinea pig brain S-adenosylmethionine (SAM)-dependent N-methyltransferase activity toward physiologically relevant beta-carboline (BC) substrates was examined with reverse-phase HPLC and radiochemical detection. Representative BCs, norharman and harmine, were enzymatically methylated on the 2[beta]-nitrogen by [3H]CH3-SAM in undialyzed homogenates to yield 2[beta]-methylated BCs and subsequently on the 9[indole]-nitrogen to generate 2,9-dimethylated BC products. This may be the first account of mammalian indole N-methyl transfer. There was no HPLC evidence for 9-methyl BC or (from carbon methylation) 2,6-dimethyl BC products. Capillary gas chromatography-mass spectrometry analysis confirmed the structures of the 2,9-dimethyl and 2-methyl products of norharman. The 2[beta]- and 9[indole]-N-methylation activities were mainly in the nuclear fractions and were negligible in undialyzed cytosol. This differs from the cytosolic SAM dependent N-methylations reported with other azaheterocyclics, including 1,2,3,4 tetrahydro-BCs. The involvement of a single enzyme was suggested because the two N-methyl transfers with BC substrate had similar subcellular activity patterns, regional brain distributions, and Km and Vmax values. Sequential N-methylation of various BCs that have been observed in vivo may be a unique route to centrally retained N2,N9-dimethylated beta-carbolinium ions. Because they resemble the synthetic parkinsonian toxicant, N-methyl-4-phenylpyridinium, with respect to structure and neurotoxic activity, such "bioactivated" carbolinium ions could be endogenous causative factors in Parkinson's disease. PMID- 1629726 TI - Identification of a GM1-binding protein on the surface of murine neuroblastoma cells. AB - S20Y murine neuroblastoma cells appear to express a protein component(s) able to adhere specifically to the oligosaccharide portion of GM1 (oligo-GM1). To identify proteins with which the oligo-GM1 becomes closely associated, a radiolabeled (125I), photoactivatable derivative of oligo-GM1 was prepared. This was accomplished by reductive amination of the glucosyl moiety of oligo-GM1 to 1 deoxy-1-aminoglucitol, followed by reaction of the amine with sulfosuccinimidyl 2 (p-azidosalicylamido)ethyl-1,3'-dithiopropionate (SASD). Crosslinking studies using the photoactivatable probe indicated that it came in close proximity to a protein with an apparent molecular mass of approximately 71 kDa. In competition experiments, as little as a 10-fold molar excess of oligo-GM1 resulted in a selective reduction in labeling of this protein; preincubation with a 200-fold molar excess of siayllactose was necessary to observe the same change in the labeling pattern, lending additional support to the hypothesis that the approximately 71-kDa protein specifically associates with oligo-GM1. Cell surface location of the oligo-GM1 binding protein was confirmed using subcellular fractionation and morphological analyses. PMID- 1629725 TI - Activation of protein kinase C blocks astroglial gap junction communication and inhibits the spread of calcium waves. AB - The following two processes related to astrocytes are thought to depend on intercellular coupling through gap junctions: the spatial buffering of K+o and the spread of calcium waves in the astrocytic syncytium. We have used the following two independent methods to measure the open state of gap junctions: injection of lucifer yellow, and optical calcium imaging of calcium waves in response to probing the cells with a micropipette. The spread of lucifer yellow and calcium waves was inhibited if the cells were treated with either phorbol 12 myristate 13-acetate (PMA) or a synthetic diacylglycerol that activates protein kinase C. Down-regulation of protein kinase C by a 24-h treatment with PMA inhibited the uncoupling effect of PMA, supporting a direct involvement of protein kinase C in the regulation of astroglial gap junctions. Purinergic P2Y receptors, which are coupled to the inositol phospholipid pathway, are expressed by most astroglia in culture. Activation of the P2Y purinergic receptor with the selective agonist 2-methylthio-ATP uncoupled astroglia in a manner similar to the effect of treatment with PMA. Modulation of gap junctional conductance could isolate specific pathways within the astrocytic syncytium to form an extraneuronal information transfer network in brain. PMID- 1629727 TI - Mobilization of the readily releasable pool of acetylcholine from a sympathetic ganglion by tityustoxin in the presence of vesamicol. AB - The present experiments tested whether preganglionic stimulation and direct depolarization of nerve terminals by tityustoxin could mobilize similar or different pools of acetylcholine (ACh) from the cat superior cervical ganglia in the presence of 2-(4-phenylpiperidino)cyclohexanol (vesamicol, AH5183), an inhibitor of ACh uptake into synaptic vesicles. In the absence of vesamicol, both nerve stimulation and tityustoxin increased ACh release. In the presence of vesamicol, the release of ACh induced by tityustoxin was inhibited, and just 16% of the initial tissue content could be released, a result similar to that obtained with electrical stimulation under the same condition. When the impulse releasable pool of ACh had been depleted, tityustoxin still could release transmitter, amounting to some 10% of the ganglion's initial content. This pool of transmitter seemed to be preformed in the synaptic vesicles, rather than synthesized in response to stimuli, as tityustoxin could not release newly synthesized [3H]ACh formed in the presence of vesamicol, and hemicholinium-3 did not prevent the toxin-induced release. In contrast to the results with tityustoxin, preganglionic stimulation could not release transmitter when impulse releasable or toxin-releasable compartments had been depleted. Our results confirm that vesamicol inhibits the mobilization of transmitter from a reserve to a more readily releasable pool, and they also suggest that, under these experimental conditions, there might be some futile transmitter mobilization, apparently to sites other than nerve terminal active zones. PMID- 1629728 TI - Effect of voltage-sensitive calcium channel antagonists on the release of 5 hydroxytryptamine from rat hippocampus in vivo. AB - The effect of calcium channel antagonists on the release of 5-hydroxytryptamine from the hippocampus of the chloral hydrate-anaesthetised rat was studied using the technique of intracerebral microdialysis. As the basal concentration of 5 hydroxytryptamine was close to the limit of detection of the HPLC method (8 fmol), the 5-hydroxytryptamine reuptake inhibitor, fluoxetine (10 microM), was included in the perfusion fluid. The L-type voltage-sensitive calcium channel antagonists, PN200-110, diltiazem, and verapamil, all passed through the dialysis membrane, giving a recovery of 20-30%. The N-type voltage-sensitive calcium channel antagonist, omega-conotoxin, penetrated less readily (12% recovery). The dihydropyridine, PN200-110, adhered to the probe, resulting in an effective concentration at the membrane 30% of that in the perfusion fluid. The concentration of 5-hydroxytryptamine in the dialysate samples was reduced by 60% in the absence of calcium. The L channel antagonists had little effect on the release of 5-hydroxytryptamine, which was inhibited, in a dose-dependent manner, to a maximum of 40% by omega-conotoxin. It is concluded that, under physiological conditions, the release of 5-hydroxytryptamine from the rat hippocampus is dependent on the entry of calcium through N-type voltage-sensitive calcium channels, although another calcium channel may also be involved. PMID- 1629729 TI - Reconstitution of the brain mixed function oxidase system: purification of NADPH cytochrome P450 reductase and partial purification of cytochrome P450 from whole rat brain. AB - NADPH-cytochrome P450 reductase was purified to apparent homogeneity and cytochrome P450 partially purified from whole rat brain. Purified reductase from brain was identical to liver P450 reductase by sodium dodecyl sulfate polyacrylamide gel electrophoresis and western blot techniques. Kinetic studies using cerebral P450 reductase reveal Km values in close agreement with those determined with enzyme purified from rat liver. Moreover, the brain P450 reductase was able to function successfully in a reconstituted microsomal system with partially purified brain cytochrome P450 and with purified hepatic P450c (P450IA1) as measured by 7-ethoxycoumarin and 7-ethoxyresorufin O-deethylation. Our results indicate that the reductase and P450 components may interact to form a competent drug metabolism system in brain tissue. PMID- 1629730 TI - Amino acid release from cerebral cortex in experimental acute liver failure, studied by in vivo cerebral cortex microdialysis. AB - Both increased gamma-aminobutyric acid (GABA)-ergic and decreased glutamatergic neurotransmission have been suggested relative to the pathophysiology of hepatic encephalopathy. This proposed disturbance in neurotransmitter balance, however, is based mainly on brain tissue analysis. Because the approach of whole tissue analysis is of limited value with regard to in vivo neurotransmission, we have studied the extracellular concentrations in the cerebral cortex of several neuroactive amino acids by application of the in vivo microdialysis technique. During acute hepatic encephalopathy induced in rats by complete liver ischemia, increased extracellular concentrations of the neuroactive amino acids glutamate, taurine, and glycine were observed, whereas extracellular concentrations of aspartate and GABA were unaltered and glutamine decreased. It is therefore suggested that hepatic encephalopathy is associated with glycine potentiated glutamate neurotoxicity rather than with a shortage of the neurotransmitter glutamate. In addition, increased extracellular concentration of taurine might contribute to the disturbed neurotransmitter balance. The observation of decreasing glutamine concentrations, after an initial increase, points to a possible astrocytic dysfunction involved in the pathophysiology of hepatic encephalopathy. PMID- 1629732 TI - Novel procedure for measuring psychosine derivatives by an HPLC method. AB - We developed a sensitive and simple method to determine galactosylsphingosine and glucosylsphingosine as a 4-fluoro-7-nitrobenzofurazan autofluorescent compound, using HPLC equipped with a Showdex sugar column. Amounts of galactosylsphingosine were successfully measured in the picomole range. This novel procedure is more stable and simpler than the previous method using o-phthalaldehyde. It was applied to tissues from the twitcher mouse, an animal model of human globoid cell leukodystrophy. The amount of galactosylsphingosine was 34-102 micrograms/kg of wet tissues in control cerebrum and cerebellum, whereas in twitcher mice the range was 2,251-4,228 micrograms/kg of wet tissues. The psychosine concentration was also increased in the liver and kidney of twitcher mice, respectively, 1,513 micrograms and 1,106 micrograms/kg of wet tissue (normal liver, 125 micrograms; normal kidney, 74 micrograms/kg of wet tissue). This novel procedure is useful for the pathochemical evaluation of lysosphingolipids in various sphingolipidoses as well as in other neuropathological and cellular conditions. PMID- 1629731 TI - High sensitivity of glutamate uptake to extracellular free arachidonic acid levels in rat cortical synaptosomes and astrocytes. AB - By using both synaptosomes and cultured astrocytes from rat cerebral cortex, we have investigated the inhibitory action of arachidonic acid on the high-affinity glutamate uptake systems, focusing on the possible physiological significance of this mechanism. Application of arachidonic acid (1-100 microM) to either preparation leads to fast (within 30 s) and largely reversible reduction in the uptake rate. When either melittin (0.2-1 microgram/ml), a phospholipase A2 activator, or thimerosal (50-200 microM), which inhibits fatty acid reacylation in phospholipids, is applied to astrocytes, both an enhancement in extracellular free arachidonate and a reduction in glutamate uptake are seen. The two effects display similar dose dependency and time course. In particular, 10% uptake inhibition correlates with 30% elevation in free arachidonate, whereas inhibition greater than or equal to 60% is paralleled by threefold stimulation of arachidonate release. In the presence of albumin (1-10 mg/ml), a free fatty acid binding protein, inhibition by either melittin, thimerosal, or arachidonic acid is prevented and an enhancement of glutamate uptake above the control levels is observed. Our data show that neuronal and glial glutamate transport systems are highly sensitive to changes in extracellular free arachidonate levels and suggest that uptake inhibition may be a relevant mechanism in the action of arachidonic acid at glutamatergic synapses. PMID- 1629733 TI - Characterization of D-aspartic acid uptake by rat hippocampal slices and effect of ischemic conditions. AB - The cellular uptake of D-aspartic acid (D-Asp) as a model compound for glutamic acid transport was studied in rat hippocampal slices. D-Asp is accumulated by both Na(+)-dependent and Na(+)-independent processes in hippocampal slices, and both processes are dependent on temperature. The Na(+)-dependent uptake is assumed to be high in affinity (apparent Km = 0.17 mM), but low in capacity, whereas the Na(+)-independent uptake is much lower in affinity (Km = 2.86 mM), but higher in capacity. L-Aspartic acid, L-glutamic acid, dihydrokainic acid, and threo-3-hydroxy-DL-aspartic acid markedly inhibited the uptake of D-Asp with Na+ in the medium, whereas D-glutamic acid, glycine, and L-lysine had no significant effect. The Na(+)-dependent uptake of D-Asp was significantly reduced under "hypoglycemic," "anoxic," and "ischemic" conditions, whereas the Na(+) independent uptake was unaffected. Metabolic inhibitors such as NaCN and ICH2COOH significantly inhibited the Na(+)-dependent uptake, but not the Na(+)-independent uptake. These results suggest that the Na(+)-dependent component of D-Asp transport in rat hippocampal cells is inactivated under ischemic conditions, whereas the Na(+)-independent component is unaffected. PMID- 1629734 TI - Neuronal ganglioside increases dependent on the neuron--glia interaction in primary culture. AB - Dissociated neuronal cells from rat embryonic hemispheres were cultivated on astroglial layers. The increase in ganglioside content of the cocultures was more rapid than that of neuronal cultures seeded on polylysine surfaces for the first 24 h, and the extent of the increase was greater 7 days after inoculation, probably because of interaction between the preformed astroglial layers and the neuronal cells in vitro. The promoted expression of the a-pathway gangliosides, GM1 and GD1a, was recognized by TLC and the increase in GM1 was immunologically ascertained. The incorporation of 3H-labeled N-acetyl-D-mannosamine into GD3 and b-series gangliosides was elevated for the first 24 h. However, cocultures in which there was no contact between neuronal cells and the astroglial sheet showed no appreciable increase in incorporation. Thus, cell surface changes were induced at the membrane glycolipid level in the neuronal cells by contact with astroglial layers. The synthesis and expression of neuronal gangliosides are discussed in relation to the onset of neuron--glia interaction. PMID- 1629735 TI - Lack of in vitro ceramide formation in the PNS of trembler mice. AB - The amidification of sphingosine by acyl donors has been investigated in a microsomal fraction prepared from sciatic nerves of normal and Trembler mice. In the control, a ceramide synthesis is observed in the presence of acyl-CoAs and not with free fatty acids. The synthesis increases as a function of the protein amount and the time and is dependent on acyl-CoA concentration. The level of synthesis is highly similar to that observed in vivo after palmitate injection into the sciatic nerves of normal mice. In the mutant, there is a major abnormality because a weak synthesis (20% of the control) is observed only with high acyl-CoA concentration (greater than 200 microM), whereas in the range of the physiological acyl-CoA concentrations (less than 20 microM), there is no ceramide formation from stearoyl-CoA or lignoceroyl-CoA. PMID- 1629736 TI - Ecto-5'-nucleotidase is associated with cholinergic nerve terminals in the hippocampus but not in the cerebral cortex of the rat. AB - The extracellular catabolism of exogenously added AMP was studied in immunopurified cholinergic nerve terminals and in slices of the hippocampus and cerebral cortex of the rat. AMP (10 microM) was catabolized into adenosine and inosine in hippocampal cholinergic nerve terminals and in hippocampal slices, as well as in cortical slices. IMP formation from extracellular AMP was not detected. alpha, beta-Methylene ADP (100 microM) inhibited almost completely the extracellular catabolism of AMP in these preparations. The relative rate of catabolism of AMP was greater in hippocampal slices than in cortical slices. AMP was virtually not catabolized when added to immunopurified cortical cholinergic nerve terminals, although ATP could be catabolized extracellularly under identical conditions. The comparison of the relative rates of catabolism of exogenously added AMP, calculated from the amount of AMP catabolized after 5 min, in hippocampal cholinergic nerve terminals and in hippocampal slices revealed a nearly 50-fold enrichment in the specific activity of ecto-5'-nucleotidase upon immunopurification of the cholinergic nerve terminals from the hippocampus. The results suggest that there is a regional variation in the subcellular distribution of ecto-5'-nucleotidase activity in the rat brain, the ecto-5' nucleotidase in the hippocampus being closely associated with the cholinergic nerve terminals, whereas in the cerebral cortex ecto-5'-nucleotidase activity seems to be located preferentially outside the cholinergic nerve terminals. PMID- 1629737 TI - The postsynaptic density: constituent and associated proteins characterized by electrophoresis, immunoblotting, and peptide sequencing. AB - The proteins of the postsynaptic density (PSD) fraction of cerebral cortex were resolved by two-dimensional electrophoresis (2DE) and more than 30 proteins identified by characteristic 2DE mobility, immunoblotting with specific antibodies, and N-terminal and peptide sequencing. The PSD fraction is enriched for spectrin, actin, tublin and microtubule associated protein II, myosin, enzymes of glycolysis, creatine kinase, elongation factor 1 alpha, and receptor protein. The three neurofilament proteins are detected but a 58-kDa protein is prominent and is, by peptide sequencing, the bovine homolog of the recently cloned 66-kDa neurofilament protein; in contrast to the latter, however, it is enriched in cerebrum compared with spinal cord. A 68-kDa protein is identified as a member of the hsp70/BiP family of proteins. A protein, designated dynamin, indicating its putative role as a microtubule motor, is identified as a major protein, is found, however, greatly enriched in the particulate fraction, and is significantly denaturant and detergent insoluble. A protein designated N ethylmaleimide-sensitive factor is also detected. Thus, two proteins implicated in vesicular transport are present in the PSD fraction. Seven polyclonal antibodies were produced to 2DE separated and electroeluted proteins of the PSD and were identified by peptide sequence analysis and 2DE profile as the hsp70/BiP homologous protein, the novel neurofilament protein synapsin IIa, pyruvate kinase, dynamin, aconitase and an unknown contaminating protein, and a 115-kDa protein that by subcellular fractionation and immunoblotting is a diagnostic PSD molecule. In addition, peptide sequences are obtained for four additional higher molecular weight proteins of the PSD that are not related at the level of primary structure to any known proteins. PMID- 1629738 TI - Binding and active transport of large analogues of acetylcholine by cholinergic synaptic vesicles in vitro. AB - A previous structure-activity investigation of acetylcholine (ACh) revealed a positive correlation between additional hydrophobic bulk and increased potency for inhibition of active transport of [3H]ACh by synaptic vesicles isolated from the electric organ of Torpedo. In the current study, several ACh analogues that are significantly larger than previously studied "false transmitters" were synthesized in the tritiated form by chemical means and tested for active transport. These are analogue 14 [(+/-)-(cis,trans)-1-benzyl-1-methyl-3 acetoxypyrrolidinium iodide], analogue 15 [(+/-)-1,1-dimethyl-3 benzoyloxypyrrolidinium iodide], and analogue 16/17 [(+/-)-(cis,trans)-1-benzyl-1 methyl-3-benzoyloxypyrrolidinium iodide]. These analogues place significant additional hydrophobic bulk on one or the other (analogues 14 and 15) or both (analogue 16/17) of the two pharmacophores of a small, conformationally constrained analogue of ACh. [3H]Analogue 14 and [3H]analogue 15 are actively transported, with Vmax values the same as or less than that of ACh, depending on the vesicle preparation. The observation that Vmax is the same for an analogue and ACh in some vesicle preparations suggests that the rate-limiting step does not involve ACh bound to the transporter. [3H]Analogue 16/17 is actively transported very poorly. Km values for ACh and for transported ACh analogues vary by up to two- to threefold in different vesicle preparations. The ACh transporter is much less selective for transported substrates than anticipated. PMID- 1629739 TI - Effect of hypothyroidism on different forms of actin in rat cerebral neuronal cultures studied by an improved DNase I inhibition assay. AB - An improved DNase I inhibition assay for the filamentous actin (F-actin) and monomeric actin (G-actin) in brain cells has been developed. Unlike other methods, the cell lysis conditions and postlysis treatments, established by us, inhibited the temporal inactivation of actin in the cell lysate and maintained a stable F-actin/G-actin ratio for at least 4-5 h after lysis. The new procedure allowed separate quantitation of the noncytoskeletal F-actin in the Triton soluble fraction (12,000 g, 10 min supernatant) that did not readily sediment with the Triton-insoluble cytoskeletal F-actin (12,000 g, 10 min pellet). We have applied this modified assay system to study the effect of hypothyroidism on different forms of actin using primary cultures of neurons derived from cerebra of neonatal normal and hypothyroid rats. Our results showed a 20% increase in the Triton-insoluble cytoskeletal F-actin in cultures from hypothyroid brain relative to normal controls. In the Triton-soluble fraction, containing the G-actin and the noncytoskeletal F-actin, cultures from hypothyroid brain showed a 15% increase in G-actin, whereas the F-actin remained unaltered. The 10% increase in total actin observed in this fraction from hypothyroid brain could be totally accounted for by the enhancement of G-actin. The mean F-actin/G-actin ratio in this fraction was about 30% higher in the cultures from normal brain compared to that of the hypothyroid system, which indicates that hypothyroidism tends to decrease the proportion of noncytoskeletal F-actin relative to G-actin. PMID- 1629740 TI - Identification and purification of calcium-independent phospholipase A2 from bovine brain cytosol. AB - Substantial amounts of phospholipase A2 activity were detected in bovine brain cytosol. The major phospholipase A2 activity was present in the precipitate at 40% saturation with solid ammonium sulfate. After the desaltate of the precipitate was loaded onto an Ultrogel AcA 54 gel filtration column, almost all the activity eluted in the void volume when chromatographed without 1 M KCl. However, when buffer with 1 M KCl was used as the eluent, two active peaks were obtained. One peak (peak I) eluted in the void volume, and the other (peak II) eluted with an apparent molecular mass of 39 kDa as compared with standards. The former was active with diacylglycero-3-phosphoethanolamine, whereas the latter was active with both diacylglycero-3-phosphoethanolamine and 1-alk-1'-enyl-2 acylglycero-3-phosphoethanolamine (plasmenylethanolamine). The apparent molecular mass of peak I was estimated to be 110 kDa as compared with standards on an Ultrogel AcA 34 gel filtration column. Both peaks were purified further with a hydrophobic chromatography column (AffiGel 10 coupled with plasmenylethanolamine) and then by high-resolution liquid chromatography on an MA7Q column. The phospholipase A2 obtained from peak II migrated as one main band with a 40-kDa molecular mass and two minor bands with 14- and 25-kDa molecular masses. Phospholipase A2 obtained from peak I eluted as a single peak on high-resolution liquid chromatography but contained two bands with apparent molecular masses of 100 and 110 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629742 TI - Diadenosine tetraphosphate is co-released with ATP and catecholamines from bovine adrenal medulla. AB - Secretion of adenosine(5')tetraphospho(5')adenosine (Ap4A) and ATP from perfused bovine adrenal glands stimulated with acetylcholine or elevated potassium levels was measured and compared with that of catecholamines. We have found a close correlation between the release of Ap4A and catecholamines elicited with all the secretagogues used in the presence of either Ca2+ or Ba2+, suggesting co-release of both constituents from the chromaffin granules. By contrast, ATP secretion, as measured with luciferase, showed a significantly different time course regardless of the secretagogue used. ATP secretion consistently decreased after 1-2 min of stimulation at a time when Ap4A and catecholamine secretions were still increasing. Measures of degradation of injected [3H]ATP to the gland during stimulation showed little difference in the level of uptake or decomposition of ATP throughout the pulse. However, a reexamination of ATP secretion by monitoring its products of degradation (AMP, adenosine, and inosine) by HPLC techniques showed that Ap4A, ATP, and catecholamines are indeed secreted in parallel from the perfused adrenal gland. PMID- 1629741 TI - K-252b selectively potentiates cellular actions and trk tyrosine phosphorylation mediated by neurotrophin-3. AB - K-252b, a protein kinase inhibitor, has been shown earlier to inhibit nerve growth factor actions on cholinergic neurons of the basal forebrain. In the present study, K-252b was found to prevent trophic actions of two other neurotrophins, brain-derived neurotrophic factor, and neurotrophin-3, on central cholinergic and dopaminergic neurons, peripheral sensory neurons, and PC12 pheochromocytoma cells, when used at greater than 2 microM concentration. Comparable actions of nonneurotrophin growth factors were not affected. Surprisingly, at 0.1-100 nM, K-252b selectively enhanced the trophic action of neurotrophin-3 on central cholinergic neurons, peripheral sensory neurons, and PC12 cells. In PC12 cells, K-252b potentiated the neurotrophin-3-induced tyrosine phosphorylation of trk, a protein kinase responsible for transmitting neurotrophin signals. Of the three structurally related nerve growth factor inhibitors, K-252a, K-252b, and staurosporine, only the first two also mediated neurotrophin-3 potentiation. These findings indicate that K-252b generally and selectively potentiates the neurotrophic action of neurotrophin-3 and suggest that this action involves trk-type neurotrophin receptors. PMID- 1629743 TI - MK-801 prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in primates. AB - In cynomologus monkeys, systemic administration of MK-801, a noncompetitive antagonist for the N-methyl-D-aspartate receptor, prevented the development of the parkinsonian syndrome induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP). MK-801 also attenuated dopamine depletion in the caudate and putamen and protected dopaminergic neurons in the substantia nigra from the degeneration induced by the neurotoxin. Nevertheless, 7 days after MPTP administration in the caudate and putamen of monkeys also receiving MK-801, the levels of toxic 1-methyl-4-phenylpyridinium were even higher than those measured in monkeys receiving MPTP alone. This indicates that the protective action of MK 801 is not related to MPTP metabolism and strongly suggests that, in primates, the excitatory amino acids could play a crucial role in the mechanism of the selective neuronal death induced by MPTP. PMID- 1629744 TI - Quantitative autoradiography of dihydrorotenone binding to complex I of the electron transport chain. AB - Defective complex I activity has been linked to Parkinson's disease and Huntington's disease, but little is known of the regional distribution of this enzyme in the brain. We have developed a quantitative autoradiographic assay using [3H]dihydrorotenone ([3H]DHR) to label and localize complex I in brain tissue sections. Binding was specific and saturable and in the cerebellar molecular layer had a KD of 11.5 +/- 1.3 nM and a Bmax of 11.0 +/- 0.4 nCi/mg of tissue. Unlabeled rotenone and 1-methyl-4-phenylpyridinium ion competed effectively for DHR binding sites. Binding was markedly enhanced by 100 microM NADH. The distribution of complex I in brain, as revealed by DHR autoradiography, is unique but somewhat similar to that of cytochrome oxidase (complex IV). This assay may provide new insight into the roles of complex I in brain function and neurodegeneration. PMID- 1629745 TI - Brain levels of microtubule-associated protein tau are elevated in Alzheimer's disease: a radioimmuno-slot-blot assay for nanograms of the protein. AB - The microtubule-associated protein tau, which stimulates the assembly of alpha beta tubulin heterodimers into microtubules, is abnormally phosphorylated in Alzheimer's disease (AD) brain and is the major component of paired helical filaments. In the present study, the levels of tau and abnormally phosphorylated tau were determined in brain homogenates of AD and age-matched control cases. A radioimmuno-slot-blot assay was developed, using a primary monoclonal antibody, Tau-1, and a secondary antibody, antimouse 125I-immunoglobulin G. To assay the abnormally phosphorylated tau, the blots were treated with alkaline phosphatase before immunolabeling. The levels of total tau were about eightfold higher in AD (7.3 +/- 2.7 ng/micrograms of protein) than in control cases (0.9 +/- 0.2 ng/micrograms), and this increase was in the form of the abnormally phosphorylated protein. These studies indicate that the abnormal phosphorylation- not a decrease in the level of tau--is a likely cause of neurofibrillary degeneration in AD. PMID- 1629746 TI - Analysis of muscarinic receptor subtypes in the mouse cochlea by means of the polymerase chain reaction. AB - Total RNA was extracted with guanidine thiocyanate from the cochleas of 16-day old CBAJ mice. The mRNA was purified from the total RNA using oligo-dT cellulose, and the mRNA was treated with DNase to degrade genomic DNA. After reverse transcription, resulting cDNA was amplified by polymerase chain reaction (PCR), using primers specific for the nucleotide sequences m1-m5, representing subtypes of muscarinic acetylcholine receptors. PCR products corresponding to subtypes m1, m3, and m5, but not to m2 and m4, were amplified. These results suggest that muscarinic acetylcholine receptors of these odd-numbered subtypes are expressed in the mammalian cochlea. PMID- 1629747 TI - Aztreonam plus vancomycin versus gentamicin plus piperacillin as empirical therapy for the treatment of fever in neutropenic patients: a randomised controlled study. AB - The efficacy of aztreonam in combination with vancomycin was compared with that of gentamicin plus piperacillin as empirical antibiotic treatment for fever in 61 neutropenic patients. Aztreonam plus vancomycin was as effective, but no more effective, than gentamicin plus piperacillin. Aztreonam showed excellent clinical and in vitro efficacy against Gram-negative pathogens. Failure to respond to aztreonam plus vancomycin was, in most cases, due to presumed or documented fungal infection; by contrast, failure to respond to gentamicin plus piperacillin was frequently to be due to resistant or superadded infection with Gram-positive bacteria. PMID- 1629748 TI - Short vs. long cotrimoxazole courses in eradicating bacteriuria in the elderly. AB - To test whether longer duration of treatment of asymptomatic bacteriuria in old age could improve the efficacy of cotrimoxazole therapy, three regimens were given to 75 ambulant bacteriuric residents of a retirement home, aged greater than or equal to 68 years. The groups and regimens were: A:23 subjects (160/800 mg b.i.d. orally x 3 days). B: 24 subjects (160/800 mg i.m. x 10 days); C: 28 subjects (160/800 mg b.i.d. orally x 20 days). One week, one month and five months post-therapy urines were negative in 78.3% vs 52.9% vs 42.9% of group A, in 54.2% vs 56.5% vs 50% of group B and in 57.1% vs 60.7% vs 68% of group C subjects respectively. The data indicate that: 1) the efficacy of any schedule is only moderate irrespective of the presence of antibody-coated bacteria in urine; 2) a 3-day course appears more effective at one week post-therapy; 3) at one and five months greater than or equal to 50% of the subjects were infection-free, the 20 day treatment resulting in fewer failures; 4) subjects with long-term eradication had no mobility problem, low serum creatinine and a normal urinary tract as seen by ultrasound. PMID- 1629749 TI - Frequency and transferability of trimethoprim and sulfonamide resistance in methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. AB - A total of 374 Staphylococcus aureus and 126 Staphylococcus epidermidis strains from 14 countries were studied for their resistance to methicillin, trimethoprim (Tp) and sulfonamides (Su), alone and combined (TpSu). The frequency of resistance to Tp, Su and TpSu was much higher in methicillin-resistant S. epidermidis (MRSE) than in methicillin-resistant S. aureus (MRSA). Considerable differences, however, existed in isolates from different countries. Resistance to Tp, Su or TpSu in MRSA was low or absent in isolates from Switzerland, Spain, Japan, Mexico, Argentina and Chile, but high in isolates from Germany and Brazil. High level Tp resistance mostly resided on large plasmids. It could be transferred in 17 out of 97 strains. Su resistance was never cotransferred. Strains cured of their large Tp resistance plasmids remained Su-resistant, which suggests a chromosomal location of Su resistance. PMID- 1629750 TI - Effect of a broad-spectrum cephalosporin on the oral and intestinal microflora in patients undergoing colorectal surgery. AB - The influence of ceftriaxone on oral and intestinal flora was investigated in 10 patients undergoing colorectal surgery. Ceftriaxone was given intravenously in one 2g dose before anesthesia. Saliva and feces samples were collected and analyzed on day 0, 3, 5, 14 and 28 after drug administration. All specimens were cultured quantitatively for aerobic and anaerobic microorganisms; representative colonies of each morphologic type of organism cultured were identified. The oral aerobic flora was somewhat affected by the administration of ceftriaxone. In all patients the number of Streptococci, Staphylococci and Neisseria decreased during the 5 days after ceftriaxone administration. No significant changes in the number of anaerobic commensal occurred. The oral microflora of all patients after 14 days had returned to normal. The aerobic fecal flora was considerably affected: in all patients enterobacteria were eliminated or strongly suppressed. Only minor changes in the number of aerobic gram-positive bacteria were observed, and the anaerobic intestinal flora showed only minor alterations. On day 28 the intestinal flora were normalized in all respects. No new colonizing microorganisms were isolated during the investigation period and no colonization with ceftriaxone-resistant bacteria was observed. No postoperative infection occurred and no adverse effects were registered. PMID- 1629751 TI - The influence of serum proteins on biological activity of anticandidal peptides containing N3-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid. AB - The binding of several anticandidal peptides containing N3-(4-methoxyfumaroyl)-L 2,3-diaminopropanoic acid (FMDP) to serum proteins was studied using equilibrium dialysis. The affinity of these FMDP-peptides for serum albumin was low and well correlated with their biological activity against Candica albicans ATCC 26278 in serum albumin solution. This binding did not affect the biological activity of FMDP-peptides. On the other hand, substantial raising of MIC values was observed when anticandidal activity of FMDP peptides was assayed in the presence of complete serum proteins. This effect was likely to be a result of interaction with non-albumin components of serum proteins. Preliminary evidence points to the possibility of non-specific interaction with components containing sulfhydryl groups. In this study Nva-FMDP-Nva peptide was shown to be the most active compound in the serum protein solution. Moreover Nva-FMDP-Nva was most resistant to inactivation by serum components in comparison to other FMDP-peptides. PMID- 1629752 TI - Relation of changes in hepatitis B virus replication markers to the outcome of interferon treatment in patients with chronic hepatitis. AB - The relationship between the behavior of hepatitis B virus (HBV) replication markers and the response to treatment with recombinant alpha-2b interferon (IFN) was investigated in 11 patients with chronic hepatitis. At the end of 6 months of treatment, 4 patients showed a complete response to IFN: 2 more patients had seroconversion to HBeAb after 8 and 9 months of follow-up, respectively. The response to IFN was partial in the remaining patients. Pre-treatment levels of HBV DNA in patients showing complete response were lower than pre-treatment levels in patients with partial response: in addition, serum HBV DNA clearance during the treatment was associated with sustained remission more frequently than changes in the HBeAg/HBeAb system. PMID- 1629753 TI - Trimethoprim-sulfamethoxazole plus amikacin as first-line therapy and imipenem/cilastatin as second empirical therapy in febrile neutropenic patients with hematological disorders. AB - One hundred and thirty-nine consecutive episodes of fever were evaluated in 55 patients with hematological disorders during persistent neutropenia. In 121 instances, patients were given trimethoprim-sulfamethoxazole + amikacin (TMP/SMZ + AMI) as an initial antibiotic regimen with clinical success in 51% (i.e. antibiotic treatment was not changed within the first 7 days). Imipenem/cilastatin (I/C) therapy was instituted in: (a) 22 episodes with clinical failure and fever of unknown origin during TMP/SMZ + AMI therapy and (b) 18 episodes with a second fever episode during initially successful TMP/SMZ + AMI therapy. The response rate for all 40 I/C treated episodes was 80%. One neutropenic patient in the whole series died from infectious complications within four weeks from institution of therapy. TMP/SMZ+AMI seems to be a safe and inexpensive "standard" antibiotic regimen in neutropenic patients. I/C appears to have good efficacy when used as secondary therapy after failure with TMP/SMZ+AMI. PMID- 1629754 TI - Organizing principles for single joint movements: V. Agonist-antagonist interactions. AB - 1. Normal human subjects made discrete elbow flexions in the horizontal plane under different task conditions of initial or final position, inertial loading, or instruction about speed. We measured joint angle, acceleration, and electromyographic signals (EMGs) from two agonist and two antagonist muscles. 2. For many of the experimental tasks, the latency of the antagonist EMG burst was strongly correlated with parameters of the first agonist EMG burst defined by a single equation, expressed in terms of the agonist's hypothetical excitation pulse. Latency is proportional to the ratio of pulse duration to pulse intensity, making it proportional to movement distance and inertial load and inversely proportional to planned movement speed. However, these rules are not sufficient to define the timing of every possible single joint movement. 3. For movements described by the speed-insensitive strategy, the quantity of both antagonist and agonist muscle activity can be uniformly associated with selected kinetic measures that incorporate muscle force-velocity relations. 4. For movements collectively described by the speed-sensitive strategy, (i.e., that have direct or indirect constraints on speed), no single rule can describe all the combinations of agonist-antagonist coordination that are used to perform these diverse tasks. 5. Estimates of joint viscosity were made by calculating the amount of velocity-dependent torque used to terminate movements on target. These estimates are similar to those that have previously been made of limb viscosity during postural maintenance. They imply that a significant component of muscle activity must be used to overcome these forces. 6. These and previous results are all consistent with a dual-strategy hypothesis for those single-joint movements that are sufficiently fast to require pulse-like muscle activation patterns. The major features of such patterns (pulse intensities, durations, and latencies) are determined by central commands programmed in advance of movement initiation. The selection between speed-insensitive or speed-sensitive rules of motoneuron pool excitation is implicitly specified by the nature of speed constraints of the movement task. PMID- 1629755 TI - Response of auditory units in the barn owl's inferior colliculus to continuously varying interaural phase differences. AB - 1. We studied the response of single units in the central nucleus of the inferior colliculus (ICc) of the barn owl (Tyto alba) to continuously varying interaural phase differences (IPDs) and static IPDs. Interaural phase was varied in two ways: continuously, by delivering tones to each ear that varied by a few hertz (binaural beat, Fig. 1), and discretely, by delaying in fixed steps the phase of sound delivered to one ear relative to the other (static phase). Static presentations were repeated at several IPDs to characterize interaural phase sensitivity. 2. Units sensitive to IPDs responded to the binaural beat stimulus over a broad range of delta f(Fig. 4). We selected a 3-Hz delta f for most of our comparative measurements on the basis of constraints imposed by our stimulus generation system and because it allowed us to reduce the influence of responses to stimulus onset and offset (Fig. 3A). 3. Characteristic interaural time or phase sensitivity obtained by the use of the binaural beat stimulus were comparable with those obtained by the use of the static technique (Fig. 5; r2 = 0.93, Fig. 6). 4. The binaural beat stimulus facilitated the measurement of characteristic delay (CD) and characteristic phase (CP) of auditory units. We demonstrated that units in the owl's inferior colliculus (IC) include those that are maximally excited by specific IPDs (CP = 0 or 1.0) as well as those that are maximally suppressed by specific IPDs (CP = 0.5; Figs. 7 and 8). 5. The selectivity of units sensitive to IPD or interaural time difference (ITD) were weakly influenced by interaural intensity difference (IID).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629756 TI - Response selectivity of neurons in area MT of the macaque monkey during reversible inactivation of area V1. AB - 1. Behavioral results in the monkey and clinical studies in human show remarkable residual visual capacities after a lesion of area V1. Earlier work by Rodman et al. demonstrated that visual activity can be recorded in the middle temporal area (MT) of the macaque monkey several weeks after a complete lesion of V1. These authors also tested the effect of a reversible block of area V1 on the visual responses of a small number of neurons in area MT and showed that most of these cells remain visually responsive. From the results of that study, however, it is difficult to assess the contribution of area 17 to the receptive-field selectivity of area MT neurons. To address this question, we have quantitatively measured the effects of a reversible inactivation of area 17 on the direction selectivity of MT neurons. 2. A circular part of the opercular region of area V1 was reversibly inactivated by cooling with a Peltier device. A microelectrode was positioned in the lower layers of V1 to control the total inactivation of that area. Eighty percent of the sites recorded in the retinotopically corresponding region of MT during inactivation of V1 were found to be visually responsive. The importance of the effect was assessed by calculating the blocking index (0 for no effect, 1 for complete inactivation). Approximately one-half of the quantitatively studied neurons gave a blocking index below 0.6, illustrating the strong residual responses recorded in many neurons. 3. Receptive-field properties were examined with multihistograms. It was found that, during inactivation of V1, the preferred direction changed for most neurons but remained close to the preferred direction or to its opposite in the control situation. During inactivation of V1, the average tuning curve of neurons became broader mostly because of strong reductions in the response to directions close to the preferred and nonpreferred. Very little change was observed in the responses for directions at 90 degrees to the optimal. These results are consistent with a model in which direction selectivity is present without an input from V1 but is reinforced by the spatial organization of this excitatory input. 4. Residual responses were found to be highly dependent on the state of anesthesia because they were completely abolished by the addition of 0.4-0.5% halothane to the ventilation gases. Finally, visual responses were recorded in area MT several hours after an acute lesion of area 17.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1629757 TI - Activity of single neurons in the monkey amygdala during performance of a visual discrimination task. AB - 1. The activity of single neurons was recorded extracellularly from the monkey amygdala while monkeys performed a visual discrimination task. The monkeys were trained to remember a visual stimulus during a delay period (0.5-3.0 s), to discriminate a new visual stimulus from the stimulus, and to release a lever when the new stimulus was presented. Colored photographs (human faces, monkeys, foods, and nonfood objects) or computer-generated two-dimensional shapes (a yellow triangle, a red circle, etc.) were used as visual stimuli. 2. The activity of 160 task-related neurons was studied. Of these, 144 (90%) responded to visual stimuli, 13 (8%) showed firing during the delay period, and 9 (6%) responded to the reward. 3. Task-related neurons were categorized according to the way in which various stimuli activated the neurons. First, to evaluate the proportion of all tested stimuli that elicited changes in activity of a neuron, selectivity index 1 (SI1) was employed. Second, to evaluate the ability of a neuron to discriminate a stimulus from another stimulus, SI2 was employed. On the basis of the calculated values of SI1 and SI2, neurons were classified as selective and nonselective. Most visual neurons were categorized as selective (131/144), and a few were characterized as nonselective (13/144). Neurons active during the delay period were also categorized as selective visual and delay neurons (6/13) and as nonselective delay neurons (7/13). 4. Responses of selective visual neurons had various temporal and stimulus-selective properties. Latencies ranged widely from 60 to 300 ms. Response durations also ranged widely from 20 to 870 ms. When the natures of the various effective stimuli were studied for each neuron, one-fourth of the responses of these neurons were considered to reflect some categorical aspect of the stimuli, such as human, monkey, food, or nonfood object. Furthermore, the responses of some neurons apparently reflected a certain behavioral significance of the stimuli that was separate from the task, such as the face of a particular person, smiling human faces, etc. 5. Nonselective visual neurons responded to a visual stimulus, regardless of its nature. They also responded in the absence of a visual stimulus when the monkey anticipated the appearance of the next stimulus. 6. Selective visual and delay neurons fired in response to particular stimuli and throughout the subsequent delay periods. Nonselective delay neurons increased their discharge rates gradually during the delay period, and the discharge rate decreased after the next stimulus was presented. 7. Task-related neurons were identified in six histologically distinct nuclei of the amygdala.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1629758 TI - On oscillating neuronal responses in the visual cortex of the monkey. AB - 1. Recent studies of visual processing in the cat have shown stimulus-related oscillations in the 30- to 70-Hz range. We sought to replicate these findings in the monkey. 2. We recorded multiunit activity (MUA) and local field potentials (LFP) in areas V1 and middle-temporal area (MT), and MUA from the inferotemporal cortex (IT) of monkeys (Macaca fuscata). Recordings in all areas were made under conditions of anesthesia as close as possible to those in previous studies of oscillating responses in the cat. In addition, we recorded MUA in the IT of behaving monkeys while the monkeys performed a face discrimination task. 3. In areas V1 and MT, LFP power spectra showed broadband increases (1-100 Hz) in amplitude on stimulation by swept optimally oriented light bars, and not a shift in power from low to midfrequency, as has been reported in the cat. 4. MUA autocorrelograms (ACGs) classified by fitting Gabor functions, showed oscillations at approximately 10% of recording sites in V1 and MT, but these oscillations were in the alpha range (12-13 Hz). 5. MUA ACGs from IT in the anesthetized monkey showed no oscillations. 6. For MUA ACGs from IT in the behaving monkey, only two recording sites (out of 50) showed an oscillating response, with frequencies of 44 and 48 Hz. One oscillating response was associated with stimulation, and the other was associated with the absence of stimulation. 7. The very low incidence in the monkey of oscillating responses in the 30- to 70-Hz range (2 in 424 recordings made at 142 recording sites) and the absence of stimulus dependence suggest that such oscillations are unlikely to serve a function in the monkey, and that there may be a species difference between monkey and cat in the dynamics of neural activity in the visual cortex. 8. We found that methods of classifying responses as oscillating used in some of the studies of the cat may have led to overestimation of both the number of sites showing oscillation and the number of pairs of sites showing phase coherence. These problems arise from the failure to take account of badness of fit between Gabor functions and their corresponding ACGs, and from Gabor functions "ringing" in response to short phasic phenomena that could be consistent with nonoscillatory activity. PMID- 1629759 TI - Role of monkey midbrain near-response neurons in phoria adaptation. AB - 1. One striking characteristic of the way in which accommodation and convergence of the eyes are organized is that although the two responses are usually tightly coupled, a brief period of binocular viewing through prisms that require extra convergence brings about a persistent, adaptive alteration in the relationship between the two responses: the vergence during monocular viewing of a target at a given distance is biased in a convergent direction. We sought to discover the role of the near-response neurons we have previously described in the monkey midbrain in such phoria adaptation. 2. Phoria adaptation was produced in two monkeys by having them view binocularly stereoscopic targets under conditions that mimicked prism viewing, i.e., the mirrors of the stereoscope were set so as to require more convergence than that associated with a real target at the same distance as the images seen in the stereoscope. The activity of 57 near-response neurons located dorsally and dorsolaterally to the oculomotor nucleus was recorded before and after adaptation while the monkeys monocularly viewed targets at a range of distances. 3. Comparison of a neuron's response in normal binocular viewing with the response when the accommodation and vergence stimuli were in conflict allowed us to distinguish 24 neurons that behaved as though they were related exclusively to the vergence response. 5 neurons that behaved as though they were exclusively related to the accommodation response, and 12 neurons whose firing was not so simply related to either response. We were unable to classify the remaining 16 near-response cells by this method. 4. In accommodation-related neurons, the relationship between firing rate and accommodation did not alter, or only altered slightly, when the animal's phoria was adapted. 5. The relationship between firing rate and vergence was unaltered by phoria adaptation in only a small proportion of vergence-related neurons, showing that most neurons do not carry the entire signal responsible for phoria adaptation. On the other hand, in the majority of vergence-related neurons the relationship between firing rate and accommodation was altered by phoria adaptation, showing that most neurons do carry part of the phoria adaptation signal. 6. The implication is that the increase in vergence observed after adaptation is mediated at more than one site. A proportion of the phoria adaptation signal is present at the level of the midbrain vergence-related neurons, with the remainder of the signal being added later, presumably at the motoneurons. PMID- 1629760 TI - Expression of motor learning in the response of the primate vestibuloocular reflex pathway to electrical stimulation. AB - 1. The vestibuloocular reflex (VOR) undergoes long-term adaptive changes in the presence of persistent retinal image motion during head turns. Previous experiments using natural stimuli have provided evidence that the VOR is subserved by parallel pathways, including some that are modified during learning and some that are not. We have used electrical stimulation of the vestibular labyrinth to investigate the temporal properties of the signals that are transmitted through the modified pathways. 2. Electrodes were implanted chronically in the superior semi-circular canal, the horizontal canal, or the vestibule for electrical activation of the vestibular afferents. Learning was induced by fitting the monkeys with spectacles that magnified or miniaturized vision. Before, during, and after motor learning, we measured the eye movements evoked by electrical stimulation of the labyrinth as well as the gain of the VOR, defined as eye speed divided by head speed during natural vestibular stimulation in the dark. 3. Trains of pulses applied to the labyrinth caused the eyes to move away from the side of stimulation with an initial rapid change in eye velocity followed by a steady-state plateau. Changes in the gain of the VOR caused large changes in the trajectory and magnitude of eye velocity during the plateau, showing that our stimulating electrodes had access to the modified pathways. 4. A single, brief current pulse applied to the labyrinth evoked an eye movement that had a latency of 5 ms and consisted of a pulse of eye velocity away from the side of the stimulation followed by a rebound toward the side of stimulation. To quantify the effect of motor learning on these eye movements, we pooled the data across different VOR gains and computed the slope of the relationship between eye velocity and VOR gain at each millisecond after the stimulus. We refer to the slope as the "modification index." 5. In comparison with the evoked eye velocity, the modification index took longer to return to baseline and showed a large peak at the time of the rebound in eye velocity. Increases in stimulus current increased both the amplitude and the duration of the modification index and revealed several later peaks. These observations suggest that the full expression of motor learning requires activation of multisynaptic pathways and recruitment of primary vestibular afferents with higher thresholds for electrical stimulation. 6. The modification index was almost always positive during the initial deflection in eye velocity, and the latency of the first change in the modification index was usually the same as the latency of the evoked eye movement.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1629761 TI - Changes in the response states of primate spinothalamic tract cells caused by mechanical damage of the skin or activation of descending controls. AB - 1. The responses of a population of 318 spinothalamic tract (STT) cells to mechanical stimulation of the skin were recorded in anesthetized macaque monkeys by several teams of investigators. The responses were subjected to k-means cluster analysis, a multivariate statistical procedure. 2. For an analysis that pertained to the responsiveness of the neurons, the mean responses to four standard mechanical stimuli (Brush, Pressure, Pinch, and Squeeze) were used. Although no true clusters were found, the cells could be partitioned into four groups (called clusters a, b, c, and d) that responded progressively more vigorously to the stimuli. 3. For an analysis that pertained to the selectivity of the cells for various stimulus intensities, from innocuous to highly noxious, the data were normalized by taking the ratio of the mean response evoked by each stimulus to the sum of the responses and multiplying by 100. This procedure does not have a bias toward selection of any particular number of clusters and resulted in three clusters of STT cells. 4. Cluster 1 STT cells responded best to Brush. Cluster 2 cells responded weakly to Brush and Pressure and maximally to Pinch. Cluster 3 cells responded weakly to Brush, Pressure, and Pinch and maximally to Squeeze. 5. The response states of STT cells with respect to mechanical stimulation of the skin can be defined by their cluster assignments on the basis of the responsiveness (clusters a-d) and selectivity (clusters 1-3) of the cells. The response states of newly recorded STT cells can be determined by discriminant analysis from the nearest centroids of the two types of clusters in the reference population of STT cells. 6. No consistent changes in response state were detected when a second series of mechanical stimuli was applied 1 cm from the site stimulated initially or when the stimulus series was alternately repeated at the initial site and at progressively more proximal sites. However, when the stimulus series was applied five times to the initial site, the response state of five of eight cells tested showed a change. Although a change in response state required repetitive damage, even a single stimulus series increased background activity and responses to Brush at undamaged sites. 7. The background activity and responses to Brush and Pressure of all five STT cells recorded in the superficial laminae increased after repeated testing. The background activity of five STT cells recorded in the nucleus proprius also increased, but the responses of only three of the cells to Brush and Pressure increased.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1629762 TI - Control of trigeminal motoneurons from the cerebellar interpositus nucleus of the guinea pig. AB - 1. Effects of stimulation of the cerebellar interpositus nucleus (IPN) on jaw reflexes and trigeminal motoneurons were studied along with the route responsible for the effects in ketamine-anesthetized guinea pigs. 2. Stimulation in the IPN evoked a bilateral, ipsilaterally dominant, short-latency reciprocal effect on jaw reflexes: a depression of the jaw-closing masseteric reflex and a facilitation of the jaw-opening digastric reflex. This reciprocal phase was followed by a non-reciprocal facilitatory phase. 3. Stimulation in the IPN evoked a short-latency, strychnine-sensitive inhibitory postsynaptic potential (IPSP) followed by a rebound depolarizing potential in the jaw-closing masseter motoneurons (MAMNs) and an excitatory postsynaptic potential (EPSP) in the jaw opening anterior digastric motoneurons (ADMNs). The time course of the intracellular response of MAMNs to the IPN stimulation was similar to that of the IPN-induced effects on the jaw-closing reflex. In contrast, the duration of the IPN-induced EPSP in ADMNs was shorter than the IPN-induced facilitation of the jaw-opening reflex. 4. After the IPN neurons were lost by injection of kainic acid into the nucleus, the reciprocal effect of the IPN stimulation on the jaw reflexes could not be seen, even though the projection fibers from the trigeminal sensory nucleus to the IPN remained essentially intact. 5. Stimulation in the superior cerebellar peduncle (SP) induced the same reciprocal effect on the jaw reflexes as the IPN stimulation. A lesion of the SP virtually abolished the reciprocal effect on the jaw reflexes of stimulation in the IPN ipsilateral with reference to the SP lesion. 6. Transection of the brain stem at the level immediately caudal to the red nucleus did not affect the reciprocal effect of the IPN stimulation on the jaw reflexes. 7. We conclude that the IPN output bilaterally induces an inhibition of jaw-closing MAMNs and an excitation of jaw opening ADMNs, oligosynaptically by way of a direct cerebelloreticular projection system via the SP. PMID- 1629763 TI - Hypoxia decreases intracellular calcium in adult rat carotid body glomus cells. AB - 1. Carotid body chemoreceptors were removed intact from adult rats and subjected to protease and collagenase enzymatic digestion of connective tissue. 2. Recordings from the sinus nerve demonstrated that chemotransduction remains intact for at least 2-3 h after isolation, enzyme exposure, and suspension in N-2 hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered saline at room PO2. 3. After mechanical dissociation, the interrelationship between changes in extracellular PO2 and pH and relative changes in intracellular calcium (Ca2+i) were observed in glomus cells with the use of fluo-3 and confocal microscopy. 4. Brief (60-s) decreases in PO2 from 150 mmHg to near 0 mmHg, at nadir, caused a marked reduction in Ca2+i (peak delta F/F0 = -32 +/- 3%, mean +/- SE, n = 43), which rapidly recovered after reoxygenation. The decrease was reproducible from trial to trial and was also observed in HCO3(-)-buffered Ringer solution. 5. Superfusion with Ca(2+)-free HEPES saline with 1 mM ethylene glycol-bis(beta aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) blocked the hypoxia-induced increase in afferent chemoreceptor activity in vitro. Superfusion of the same solution over isolated cells for 15 min caused a large decrease in Ca2+i (-34 +/- 7%, n = 16). 6. In the presence of Ca(2+)-free HEPES, reoxygenation caused calcium fluorescence to increase. This suggests that the Ca2+ decrease during hypoxia is due, at least partially, to binding to an intracellular site. 7. Extracellular cobalt (1 mM, 15 min) also reversibly blocked the chemoreceptor response to hypoxia, in vitro, and caused a reduction in Ca2+i (delta F/F0 = -37 +/- 8%, n = 11).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629764 TI - Gustatory neural coding in the monkey cortex: L-amino acids. AB - 1. Single-neuron activity in the primary gustatory cortex of the alert cynomolgus monkey (Macaca fascicularis) was analyzed in response to a range of taste stimuli. Tastants included the four prototypical stimuli (glucose, NaCl, HCl, and quinine), fruit juice, and 12 amino acids selected for their chemical characteristics, nutritional significance, and biological importance, as well as for the availability of human psychophysical data on their perceived qualities. 2. Taste-evoked responses could be recorded from a cortical area that measured 3.5 mm in its anteroposterior extent, 2.0 mm mediolaterally, and 6.0 mm dorsoventrally. Gustatory cells constituted 4.8% of the 1,129 neurons tested. Nongustatory cells gave responses associated with mouth movements (11.1%), somatosensory stimulation (3.8%), approach or anticipation of the taste stimulus (2.2%), and tongue extension (0.4%). 3. The most effective taste stimuli were those with qualities that humans describe as salty or sweet: NaCl, monosodium glutamate, glucose, proline, glycine, and fruit juice. The least effective tastants were those rated bitter or insipid: tyrosine, tryptophan, phenylalanine, and leucine. Accordingly, 79% of the gustatory neurons responded best to glucose (46%) or NaCl (33%) among the basic stimuli; only 19% responded best to quinine (13%) or HCl (6%). One cell (2%) responded exclusively to fruit juice. 4. Cortical gustatory neurons showed a moderate breadth of sensitivity, with a mean breadth of tuning coefficient of 0.71 across 54 cells. There was no evidence of chemotopic organization in the taste cortex. 5. The taste quality of each stimulus was inferred from the relative similarity of the profiles they evoked. The clearest distinction among stimuli was between those that humans characterize as sweet versus those with other qualities. Several amino acids that have dominant sweet (glycine and proline), salty (arginine and monosodium glutamate), sour (tryptophan), or bitter (phenylalanine) components to humans evoked activity profiles that were associated with those of the appropriate prototypical stimuli. Others (cysteine and lysine) were not closely related to any single prototype. 6. Conclusions based on the responses of cortical cells in the monkey are in close agreement with those that derive from human psychophysical studies of L-amino acids, reinforcing the value of this neural model for human taste perception. PMID- 1629765 TI - Excitation of motoneurons by the Mauthner axon in goldfish: complexities in a "simple" reticulospinal pathway. AB - 1. The Mauthner cell in fish and amphibians initiates an escape behavior that has served as a model system for studies of the reticulospinal control of movement. This behavior consists of a very rapid bend of the body and tail that is thought to arise from the monosynaptic excitation of large primary motoneurons by the Mauthner cell. Recent work suggests that the excitation of primary motoneurons might be more complex than a solely monosynaptic connection. To examine this possibility, I used intracellular recording and staining to study the excitation of primary motoneurons by the M cell. 2. Simultaneous intracellular recordings from the M axon and ipsilateral primary motoneurons show that firing the M cell leads to complex postsynaptic potentials (PSPs) in the motoneurons. These PSPs usually have three components: an early, small, slow depolarization (component 1), a later, large, fast depolarization (component 2), and an even later, large, long-lasting depolarization (component 3). The first component has a latency of 0.52 +/- 0.15 (SD) ms, (n = 27) and most probably is a monosynaptic input from the M cell. This study focused on the two subsequent, less-understood parts of the PSP. Motoneurons typically fire off the second part of the PSP. This is usually (27 of 33 cells) the largest component, and it has a mean amplitude of 6.24 +/- 3.33 (SD) mV (n = 33) and a half-decay time of 0.44 +/- 0.18 (SD) ms (n = 27). The mean amplitude of the third component is 3.20 +/- 1.7 (SD) mV (n = 35), and its half-decay is 6.73 +/- 2.66 (SD) ms (n = 35). The latency of the second component averages 0.66 +/- 0.21 (SD) ms (n = 32), indicating that there are few synapses in the pathway mediating it. 3. One candidate pathway for the second component of the PSP involves a class of descending interneurons (DIs) that are monosynaptically, chemically excited by the M cell and appear in light microscopy to contact motoneurons. Simultaneous intracellular recordings from the M axon, a DI, and a primary motoneuron show that the interneurons are electrotonically coupled to motoneurons and produce the fast, second component of the PSP. Direct excitation of an interneuron leads to a very short-latency (less than 0.2 ms), fast PSP in a motoneuron similar to the second component of the PSP produced by the M axon. The short latency and fatigue resistance of this connection indicate it is electrotonic, and this is supported by evidence for DC coupling between the two cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1629766 TI - Coordination between equilibrium and head-trunk orientation during leg movement: a new strategy build up by training. AB - 1. During unilateral leg movements performed while standing, it is necessary to displace the center of gravity toward the other leg to maintain equilibrium. In addition, the orientation of particular segments, such as the head and trunk, which are used as reference values for organizing the motor act, needs to be preserved. The aim of the present study was to investigate the coordination between movement, equilibrium, and local posture. 2. Experiments were carried out on standing subjects who were instructed to raise one leg laterally to an angle of 45 degrees in response to a light. Two sources of light placed in front of the subject indicated the side on which the movement was to be performed. Three main aspects of the posturokinetic sequence were investigated in two populations, naive subjects and dancers: 1) The body weight transfer toward the supporting leg was found to have two components: first, a "ballistic" one, initiated by a thrust exerted by the moving leg; and second, an "adjustment" component during which the displacement of the center of gravity (CG) reaches a final position (steady state). An early burst in the gastrocnemius medialis of the moving leg often precedes the onset of the center of pressure change. Two differences between naive subjects and dancers were observed: first, the new CG position was almost reached in one step very near to the end of the ballistic component and required only a short adjustment in dancers, whereas in naive subjects it was reached in two steps, including a much longer adjustment component. Second, the dancers were able to minimize the CG displacement toward the supporting side; this might be because they form a better internal representation of the biomechanical limits of stability because of their long training. 2) The onset of the lateral displacement of the malleolus marker of the moving leg always occurred when the body weight had almost completed its transfer to above the support foot. This shows that the positioning of the CG in a new position compatible with equilibrium maintenance was a prerequisite for the leg movement to be performed. The relative timing of events during the posturokinetic sequence was fairly fixed in the dancers, whereas it varied from one trial to another in the naive subjects. 3) The coordination between movement, equilibrium, and head-trunk orientation involves two control strategies. An "inclination" strategy was used by the naive subjects; this consisted of an external rotation of the supporting leg around the anteroposterior ankle joint axis. A counter-rotation at the neck level ensured the stability of the interorbital line in the horizontal plane.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1629767 TI - Visual and oculomotor functions of monkey subthalamic nucleus. AB - 1. Single-unit recordings were obtained from the subthalamic nuclei of three monkeys trained to perform a series of visuooculomotor tasks. The monkeys were trained to fixate on a spot of light on the screen (fixation task). When the spot was turned off and a target spot came on, they were required to fixate on the target quickly by making a saccade. Visually guided saccades were elicited when the target came on without a time gap (saccade task). Memory-guided saccades were elicited by delivering a brief cue stimulus while the monkey was fixating; after a delay, the fixation spot was turned off and the monkey made a saccade to the remembered target (delayed saccade task). 2. Of 265 neurons tested, 95 showed spike activity that was related to some aspects of the visuooculomotor tasks, whereas 66 neurons responded to active or passive limb or body movements. The task-related activities were classified into the following categories: eye fixation-related, saccade-related, visual stimulus-related, target- and reward related, and lever release-related. 3. Activity related to eye fixation (n = 22) consisted of a sustained spike discharge that occurred while the animal was fixating on a target light during the tasks. The activity increased after the animal started fixating on the target and abruptly ceased when the target went off. The activity was unrelated to eye position. It was not elicited during eye fixation outside the tasks. The activity decreased when the target spot was removed. 4. Activity related to saccades (n = 22) consisted of a phasic increase in spike frequency that was time locked with a saccade made during the tasks. The greatest increases occurred predominantly after saccade onset. This activity usually was unrelated to spontaneous saccades made outside the task. The changes in activity typically were optimal in one direction, generally toward the contralateral side. 5. Visual responses (n = 14) consisted of a phasic excitation in response to a visual probe stimulus or target. Response latencies usually were 70-120 ms. The receptive fields generally were centered in the contralateral hemifield, sometimes extending into the ipsilateral field. The receptive fields included the foveal region in seven neurons; most of these neurons responded best to parafoveal stimulation. Peripheral stimuli sometimes suppressed the activity of visually responsive neurons. 6. Activity related to target and reward (n = 29) consisted of sustained spike discharge that occurred only when the monkey could expect a reward by detecting the dimming of the light spot that he was fixating.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1629768 TI - Midline and lateral field sound localization in the ferret (Mustela putorius): contribution of the superior olivary complex. AB - 1. The ability of ferrets to localize sound in space was determined before and after unilateral or bilateral lesions of the superior olivary complex (SOC). Lesions were made by pressure injection of kainic acid into the SOC through a stereotaxically positioned glass micropipette. The lesions destroyed the cell bodies in the superior olive without disrupting fibers of passage in the trapezoid body or other pathways in the auditory brain stem. The integrity of fibers was demonstrated by protargol staining of axonal processes and by the retrograde transport of horseradish peroxidase (HRP) from the inferior colliculus to other auditory brain stem nuclei. Behavioral tests were carried out separately for sound localization at midline and lateral field positions. Minimum audible angles were determined for single 45-ms noise bursts presented through paired loudspeakers positioned symmetrically around 0, -60, and +60 degrees azimuth. 2. Four ferrets received complete lesions of the left SOC, and two received complete lesions of the right SOC. In general, unilateral destruction of the superior olive resulted in impairments in sound localization in both left and right lateral fields. In some cases, deficits were also apparent on midline. Four additional animals received unilateral lesions that spared cells within the SOC. In most cases, deficits were apparent despite incomplete lesions of the SOC. The pattern of deficits was generally consistent with that found in animals with complete lesions. Most animals had difficulty localizing sounds in the lateral fields. 3. Four animals received bilateral lesions of the SOC. Three had complete or near-complete destruction of the superior olive on one side of the brain with relatively minor damage on the other side. Each of these animals exhibited behavioral deficits that were particularly severe ipsilateral to the more extensively damaged superior olive. One animal with complete bilateral destruction of the SOC was incapable of sound localization, even with 2-s noise bursts. This animal, however, suffered severe motor impairments after surgery that might have contributed to the apparent inability to localize sound. 4. Two animals with kainic acid lesions that caused little or no damage to the SOC were still capable of high levels of performance in tests of sound localization and had no elevation in minimum audible angles. These cases served as controls for the possible effects of nonspecific brain damage and demonstrated that kainic acid injections per se resulted in no obvious deficits in our test situation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1629769 TI - Separation of neuron types in the gustatory zone of the nucleus tractus solitarii on the basis of intrinsic firing properties. AB - 1. Whole-cell current-clamp recordings were made from neurons in the rostral nucleus tractus solitarii (NTS) in an in vitro brain slice preparation in rats. On the basis of previous investigations, these neurons are believed to be involved with processing of gustatory as well as somatosensory information. 2. Rostral NTS neurons had a mean resting membrane potential of -47 mV. The mean input resistance was 336 M omega, and by fitting a double exponential function the membrane time constant had fast (2.3 ms) and slow (20.6 ms) components. 3. Neurons were separated into four different groups on the basis of their responses to a current injection pulse paradigm consisting of membrane hyperpolarization of different magnitudes and durations immediately followed by a long (1.200 ms) depolarizing pulse. The regular repetitive discharge pattern of the first group of neurons (Group I neurons) was changed into an irregular spike train by membrane hyperpolarization. Hyperpolarization of Group II neurons either delayed the occurrence of the first action potential or increased the length of the first interspike interval in the action-potential train produced by membrane depolarization. The length of the delay was related both to the magnitude and duration of the hyperpolarizing prepulse. Hyperpolarization had the least effect on the discharge pattern of Group III neurons. The discharge pattern of Group IV neurons consisted of a short burst of action potentials that was often shortened by prior hyperpolarization of the neuron. 4. Differences exist in other intrinsic properties of the four neuron groups. Group I and III neurons were capable of initiating the highest frequency of action potentials to a 100-pA 1,200-ms depolarizing pulse. In response to a short depolarizing pulse. Group II neurons had the longest latency to the first spike and responded with the fewest action potentials. Group IV neurons tended to have higher input resistance and membrane time constants than the other neuron groups. A subset of neurons in each neuron group showed membrane afterhyperpolarizations (AHP) after depolarization-induced action-potential trains (postburst AHP). Postburst AHP amplitudes ranged from 1.0 to 12.9 mV and were of greatest magnitude in Group II neurons. Postburst AHP durations ranged from 75 to 3,538 ms and were of longest duration in neurons belonging to Group III. Group II neurons, which had the largest postburst AHP magnitude, had the shortest postburst AHP duration. 5. These results demonstrate that neurons in the rostral NTS can be separated on the basis of their intrinsic membrane properties.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1629770 TI - Local serotonergic modulation of calcium-dependent potassium channels controls intersegmental coordination in the lamprey spinal cord. AB - 1. The intersegmental coordination during undulatory locomotion in lamprey is characterized by a constant phase lag between consecutive segments, that is, the ratio between the intersegmental time lag and the cycle duration remains constant. It is shown that the spinal 5-HT (serotonin) system can, in a graded fashion, control the phase lag value from a rostrocaudal to a caudorostral lag corresponding to a reversed direction of swimming. These effects can be explained by a 5-HT-induced depression of Ca(2+)-dependent K+ channels (KCa channels) in network neurons. 2. The actions of the spinal 5-HT system were analyzed in the lamprey spinal cord preparation in vitro. Fictive swimming was induced by bath application of N-methyl-D-aspartate (NMDA). The intersegmental phase lag between ventral root burst activities was measured along the ipsilateral side of the spinal cord. The chamber with the preparation was partitioned into two pools so that the rostral and caudal halves of the preparation could be perfused independently with solutions containing the same level of NMDA (100-150 microM) with or without additional 5-HT or a 5-HT uptake blocker (citalopram). 3. Addition of 5-HT to one of these partitioned pools changed the intersegmental phase lag in this pool, whereas the cycle duration remained unchanged. It was determined by the activity in the "non-5-HT" pool. Addition of 5-HT to the caudal pool resulted in an increased rostrocaudal phase lag. When 5-HT was added to the rostral pool, on the other hand, the phase lag shifted direction to a backward coordination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629771 TI - Artificial electrical synapses in oscillatory networks. AB - 1. We use an electronic circuit to artificially electrically couple neurons. 2. Strengthening the coupling between an oscillating neuron and a hyperpolarized, passive neuron can either increase or decrease the frequency of the oscillator depending on the properties of the oscillator. 3. The result of electrically coupling two neuronal oscillators depends on the membrane potentials, intrinsic properties of the neurons, and the coupling strength. 4. The interplay between chemical inhibitory synapses and electrical synapses can be studied by creating both chemical and electrical synapses between two cultured neurons and by artificially strengthening the electrical synapse between the ventricular dilator and one pyloric dilator neuron of the stomatogastric ganglion. PMID- 1629772 TI - Connections between utricular nerve and dorsal neck motoneurons of the decerebrate cat. AB - 1. We studied connections between the utricular (UT) nerve and dorsal neck motoneurons in decerebrate cats. Electrodes were fixed in place on the UT nerve under visual observation; the other branches of the vestibular nerve were transected. 2. The N1 field potential evoked by UT nerve stimulation was recorded in the vestibular nuclei at the start of each experiment. The potential typically grew until it reached a plateau. Stimulus spread (if any) to the central ends of other nerve branches was revealed by an additional increase in N1 amplitude after the plateau was reached. 3. We recorded intracellularly from 55 motoneurons in C1 C3. Some were identified as having axons in the dorsal rami, which innervate dorsal neck muscles. Others projected in nerves that were not available for stimulation. 4. UT nerve stimulation evoked synaptic potentials in essentially all motoneurons studied. The predominant pattern consisted of disynaptic excitatory postsynaptic potentials in ipsilateral motoneurons and inhibitory postsynaptic potentials that were at least trisynaptic in contralateral motoneurons. 5. The results demonstrate the presence of short-latency connections between the utricular nerve and dorsal neck motoneurons. The functional role of this pathway remains to be investigated. PMID- 1629773 TI - Effects of the GABA uptake inhibitor tiagabine on inhibitory synaptic potentials in rat hippocampal slice cultures. AB - 1. The effects of the gamma-aminobutyric acid (GABA) uptake blocker tiagabine on inhibitory synaptic potentials (IPSPs) were examined with microelectrode and whole-cell recording from CA3 pyramidal cells in rat hippocampal slice cultures. 2. Tiagabine (10-25 microM) greatly prolonged the duration of monosynaptic IPSPs elicited in the presence of excitatory amino acid antagonists but had no effect on their amplitude. Part of the prolonged time course resulted from a GABAB receptor-mediated component that was not detectable under control conditions. 3. The mean decay time constant of the underlying GABAA receptor-mediated synaptic current was increased from 16 to 250 ms. Spontaneous miniature IPSPs recorded with whole-cell clamp were unaffected by tiagabine. Pentobarbital sodium, in contrast, increased the decay time constant of both evoked and spontaneous GABAA mediated currents. 4. Tiagabine (25 microM) inhibited spontaneous and evoked epileptiform bursting induced by increasing the extracellular potassium concentration to 8 mM. 5. We conclude that GABA uptake plays a significant role in determining the time course of evoked IPSPs and also limits the likelihood that GABAB receptors are activated. PMID- 1629774 TI - Haemorrhagic complications of intracerebral cavernomas: value of MRI. AB - The authors report a retrospective series of 10 cases of intracerebral haematomas consecutive to cavernomas and studied with MRI. The factors that led to the MRI study were the patients' age and clinical history, the site of the haematoma, the persistence of CT images and a negative arteriography. MRI showed that the haematoma was in contact with the cavernoma in 4 cases and at a distance from it in one case. In 5 cases only the cavernoma was seen at the site of the haematoma. Three patients had multiple cavernomas. In all cases, the diagnosis of cavernoma was confirmed at surgical excision. PMID- 1629775 TI - Juvenile distal cerebral ischemia: angiographic features. A study of 55 cases. AB - This study of juvenile distal cerebral ischaemia is based on 55 patients aged from 18 to 30 years. The authors describe the circumstances of discovery, as well as the clinical features and the course of the disease which may be severe and lead to non-resolutive neurological accidents and sometimes dementia. Paraclinical evaluation includes capillaroscopy, finger and toe pads biopsy (which clearly shows a pathological process with fibrocellular promontories narrowing the lumen of arterioles), and above all angiography which displays two typical signs: arterial narrowness and bands of peripheral ischaemia. In advanced forms of the disease angiography reveals classical signs of ischaemic lesions, but charateritically these are very distal. Associated abnormalities of the carotid siphon can also be found. Finally, positive CT scans show an isolated widening of the sulci which is fairly suggestive of the disease. PMID- 1629776 TI - Lhermitte-duclos disease. A rare cause of intracranial hypertension in adults. AB - In a 39-year old woman hospitalized for intracranial hypertension MRI revealed the presence of abnormal areas in the cerebellar cortex. The negative results of investigations for possible causes, as well as the appearance of radiological abnormalities and their persistence over a 6-month period incited the authors to make a tentative diagnosis of Lhermitte-Duclos disease, despite the lack of anatomicopathological evidence. PMID- 1629777 TI - MRI and CT in a case of pituitary abscess. AB - We report the case of a woman admitted for hypopituitarism of sudden onset, in whom conventional radiography, CT and MRT suggested a pituitary tumour with supra and intrasellar extensions. The surgical findings and the clinical course under antibiotic therapy transformed this diagnosis into one of pituitary abscess by a pyogenic micro-organism. Pituitary abscess is an exceptional lesion. Despite the advent of CT and MRI, its preoperative diagnosis remains difficult. However, the presence of an intrasellar expansive process with liquid centre and contrast enhanced outline should suggest the possibility of an abscess, particularly when the pituitary lesion is associated with a sphenoidal sinus effusion. PMID- 1629778 TI - Endovascular treatment of post-traumatic complex carotid-cavernous fistulas, using the arterial approach. AB - Endoarterial embolization is now the treatment of choice for traumatic carotid cavernous fistulas. However, traumatic or surgical occlusion of the carotid artery, or special cases such as unilateral double carotid-cavernous fistula, can make the transarterial approach hazardous or impossible. In such cases transvenous embolization can be an alternative treatment, although it is sometimes difficult or impossible to perform. Three cases of direct traumatic carotid-cavernous fistula and their treatments are described. In the first case, unilateral double carotid-cavernous fistula was treated with detachable balloons. In the second case, the fistula had previously been treated by trapping; percutaneous angioplasty was performed with subsequent plastic embolization of the fistula. In the third case, transarterial and transvenous approaches were impossible, and the patient was cured by combining a surgical procedure and an interventional technique. PMID- 1629779 TI - MRI anatomy of the acoustic-facial bundle in vivo. AB - In this study performed on 5 healthy volunteers the authors used oblique axial, coronal and sagittal MRI sections suitable to be anatomical configuration of the acoustic-facial bundle and were able to individualize the nerves forming this bundle throughout their course, with the sole exception of the intermediate nerve (VII2). They also analysed the relations of these nerves between themselves and with the other elements of the cerebellopontine angle. In addition, a proton density sequence (SE, 6,000/30 ms) made it possible to differentiate in vivo between the grey matter and the white matter sufficiently to individualize the principal nuclei and tracts of the brain stem, and in particular the main vestibulo-cochlear central pathways. PMID- 1629780 TI - MRI assessment of anterior callosotomy in the treatment of pharmacoresistant epilepsy. AB - Section of the anterior two-thirds of the corpus callosum is a well-known treatment of some forms of epilepsy of long duration resistant to anti-epileptic drugs and dangerous for the patient (tonic and atonic seizures). The aim of this functional surgery is to obtain the most complete rostral and caudal section of the corpus callosum without risk of disconnection syndrome. Callosotomy is seldom performed in Europe. We present our experience of magnetic resonance imaging (MRI) in the pre- and postoperative assessment of 6 patients who underwent anterior callosotomy and were followed up for more than six months. Our results were encouraging with considerable improvement of the patients' social life. PMID- 1629781 TI - Effect of alpha-tocopherol on oxidative hemolysis, as evaluated by impedance measurement. AB - Using a hypoxanthine-xanthine oxidase (HX-XOD) reaction system, the effect of vitamin E (VE) on oxidative membrane injury was studied by the impedance method. Both VE-sufficient and VE-deficient erythrocytes showed an elevation of low frequency permittivity in the early phase of reaction. In the later phase of reaction, VE-sufficient erythrocytes showed a sustained elevation in permittivity, while VE-deficient erythrocytes showed a decrease in permittivity with time. These changes consisted with the process of hemolysis in the HX-XOD system. The similarity of early phase change between VE-sufficient and VE deficient erythrocytes indicates that the HX-XOD system exerted a similar effect on both erythrocytes in the early phase. The difference in changes of later phase between the two types of erythrocytes suggests that VE suppressed the reduction in permittivity. When the results were analyzed by the Pauly-Schwan's theory based on the assumption that erythrocytes are spherical, the product of VE deficient or VE-sufficient erythrocyte size (R) and membrane capacity (Cm) showed a change similar to that in permittivity. PMID- 1629782 TI - Simultaneous determination of hydrogen, methane and carbon dioxide of breath using gas-solid chromatography. AB - The analysis of respiratory hydrogen and methane was estimated as a useful index of intestinal fermentation of undigestible carbohydrate. A simultaneous and precious analysis of these gases as well as carbon dioxide was studied. A gas impermeable multi-laminated film bag metalized by aluminum vapor was fitted to use as a storage bag; its impermeability was verified by measuring the residual rate of hydrogen after 3 months' storage. Hydrogen, methane and carbon dioxide of the breath gas even at 1 ppm could be determined simultaneously by using a gas solid chromatography installed with a photoionization detector and active carbon column. To observe the genesis of hydrogen and methane after carbohydrate ingestion, pectin, a typical water-soluble dietary fiber, was fed to healthy volunteers. Increasing excretion of pulmonary hydrogen or methane showed the sign of intestinal fermentation as the results of carbohydrate malabsorption. PMID- 1629783 TI - Metabolism of orally administered ergosterol and 7-dehydrocholesterol in rats and lack of evidence for their vitamin D biological activity. AB - Metabolism of orally administered ergosterol (Erg) and 7-dehydrocholesterol (7 DHC) in rats and their vitamin D biological activity were investigated. Most of orally administered Erg and 7-DHC were excreted in feces and the remaining sterols were absorbed through intestine. The absorbed sterols were not transported in skin as the intact forms but metabolized into brassicasterol and cholesterol, respectively, within 25 h. Neither increment of intestinal calcium absorption nor plasma calcium concentrations were observed by oral administration of Erg and 7-DHC to vitamin D-deficient rats. Therefore, we have concluded that orally administered Erg and 7-DHC have no vitamin D biological activity. PMID- 1629784 TI - Antiobesity and antidiabetic actions of a new potent disaccharidase inhibitor in genetically obese-diabetic mice, KKA(y). AB - AO-128 is a potent and structurally novel inhibitor of the intestinal disaccharidases, such as maltase and sucrase. Genetically obese-diabetic mice, KKA(y), were used to examine the acute or long-term effectiveness of this compound. AO-128 decreased a postprandial rise in blood glucose after sucrose solution loading dose-dependently; the ED50 to reduce a delta increment of blood glucose by 50% was 0.22 mg/kg. The intestinal sucrase and maltase activities were suppressed to 7 and 48% of the control levels, respectively, at a dose of 0.21 mg/kg. Four-week-old female KKA(y) mice were kept on a laboratory diet containing 10 or 50 ppm of AO-128 for 12 weeks. The high dose of AO-128 reduced food intake and body weight gain throughout the experimental period. On the other hand, the low dose reduced body weight gain for the first 4 weeks without any effect on food intake. Development of the hyperglycemia and hyperinsulinemia characteristic of KKA(y) mice was moderately prevented by the low dose, and completely by the high dose. Hypertriglyceridemia tended to be suppressed by the AO-128 treatment. The high dose decreased the hemoglobin A1 level and parametrial adipose tissue weight. Hepatomegaly and fatty liver were ameliorated by AO-128 dose-dependently. Nephropathy was ameliorated by the high dose. These findings indicate that AO-128 may be useful for treating human obesity and diabetes. PMID- 1629785 TI - Role of dihydropyrimidine dehydrogenase in the uridine nucleotide metabolism in the rat liver. AB - The activity of dihydropyrimidine dehydrogenase, which is the rate-limiting enzyme in the catabolism of pyrimidine, in livers of 5-day-old rats increased 48 h after glucocorticoid injection. The increase in the activity of dihydropyrimidine dehydrogenase by glucocorticoid administration and by aging did not decrease the uridine, uracil and sigma UMP (the sum of acid-soluble uracil 5' nucleotides) pool in liver. The increase of liver uracil by a uridine diet not increase dihydropyrimidine dehydrogenase activity. The increase of liver uracil did not increase dihydropyrimidine dehydrogenase activity. However, dihydropyrimidine dehydrogenase activity which increased after glucocorticoid treatment increased the pyrimidine-degradation rate in rat livers and hepatocytes. Pyrimidine catabolism pathway in liver may play an important role in degradation of dietary pyrimidines and pyrimidines which are administered in the form of medicines as 5-fluorouridine. PMID- 1629786 TI - Effect of ingestion of excess methionine diet on aging of erythrocytes in mice. AB - Accelerated senescence prone mice and resistant mice (SAM-P/1 and SAM-R/1) were fed 10% casein diet or that supplemented with 2.5% methionine (Met) diet for 4 weeks. Erythrocytes withdrawn from animals of each group were separated by density gradient centrifugation into four fractions of different cell density, that is, different age of erythrocytes, and were analyzed for the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and the level of oxidized protein. Excess Met decreased the specific activity of GSH-Px in each fraction and the whole population of erythrocytes in SAM-P/1 but not in SAM-R/1. The changes in SOD activities were least significant among the erythrocyte fractions of every dietary group. The oxidized protein level in cell lysate increased with the increase of cell density in both strains of animals. These results were interpreted as indicating that excess Met had a positive effect on the erythrocytes senescence, and suggested that the activity of GSH-Px may be a useful enzymatic marker for the age of erythrocytes. PMID- 1629787 TI - Lowering and delaying actions of bovine bile on plasma ethanol levels in rats. AB - The effects of bovine bile (50-400 mg.kg-1 BW) on plasma ethanol levels in male rats (6-8 weeks old) were examined. Bovine bile decreased and delayed the peak of plasma ethanol concentration: a dose response to bovine bile was observed in the concentration and time to maximum concentration of ethanol but no change in disappearance rate. These phenomena were observed in two conditions: 1) oral administration of bovine bile before oral intubation of ethanol (1.0 g.kg-1 BW) and 2) simultaneous oral administration of bovine bile and ethanol. Similar responses were obtained in taurocholic acid. No changes in hepatic alcohol and aldehyde (low Km and high Km) dehydrogenase activities were observed. The remaining rate of ethanol in stomach was significantly higher with administration of bovine bile. A negative correlation between the maximum ethanol concentration and the remaining rate of ethanol in stomach was found. The intestinal absorption rate of ethanol decreased significantly in the presence of bovine bile. These results suggest that the delay of the gastric emptying and/or the decrease of the intestinal absorption rate of ethanol are major mechanisms for the decreasing and delaying effects on plasma ethanol by bovine bile. The present paper also suggests that bile acids such as taurocholic acid may participate in the lowering and delaying actions on the peak of plasma ethanol concentration by bovine bile. PMID- 1629788 TI - Reduction of corticosterone-induced muscle proteolysis and growth retardation by a combined treatment with insulin, testosterone and high-protein-high-fat diet in rats. AB - An experiment was conducted to clarify the combined effect of simultaneous administrations of insulin (Ins, 4 units/100 g body weight/day) and testosterone propionate (TP, 2 mg/100 g body weight/day) and feeding a high-protein-high-fat (HPHF) diet (50% protein, 36% fat) on corticosterone (CTC, 10 mg/100 g body weight/day)-induced muscle proteolysis or growth retardation in young growing male rats. After 6 days prefeeding of the standard (STD) diet (25% protein, 9% fat) and the HPHF diet, hormones were injected subcutaneously for 4 days. Urine was collected every day for the 4-day experimental period to measure N tau methylhistidine excretions. The results were as follows. The growth was markedly inhibited and muscle proteolysis was accelerated by the CTC treatment. Feeding HPHF diet reduced CTC-induced muscle proteolysis and the growth retardation, and administrations of Ins and TP further reduced the proteolysis and the growth retardation. From these results, it is thought that administrations of Ins and TP and feeding HPHF diet minimize the muscle protein wasting by counteracting insulin resistance caused by CTC, and masking the CTC receptor. PMID- 1629789 TI - Accumulation of hypotaurine in tissues and urine of rats fed an excess methionine diet. AB - Hypotaurine increased in some tissues, especially in muscle, and urine of rats fed methionine excess diet. The significant depression of the body weight and food intake of rats caused by excess methionine was remarkably alleviated as previous reports and hypotaurine content in muscle and urine increased further by supplement with glycine to the excess methionine diet. PMID- 1629790 TI - Shhhhhh! Learn how to listen. PMID- 1629791 TI - The effect of Amalgambond on the flexural bond strength of dental amalgam. PMID- 1629792 TI - Pathological Society of Great Britain and Ireland. 164th Meeting. London, 8-10 January 1992. Abstracts. PMID- 1629794 TI - Algorithms to rapidly achieve and maintain stable drug concentrations at the site of drug effect with a computer-controlled infusion pump. AB - Computer-controlled infusion pumps incorporating an internal model of drug pharmacokinetics can rapidly achieve and maintain constant drug concentrations in the plasma. Although these pumps offer more accurate titration of intravenous drugs than is possible with simple boluses or constant rate infusions, the choice of the plasma as the target site is arbitrary. The plasma is not the site of drug effect for most drugs. This manuscript describes two algorithms for calculation of the infusion rates necessary for a computer-controlled infusion pump to rapidly achieve, and then maintain, the desired target concentration at the site of drug effect rather than in the plasma. PMID- 1629793 TI - A comparative investigation of hepatic clearance models: predictions of metabolite formation and elimination. AB - Liver clearance models serve to improve our understanding of the relationships between the physiological determinants and hepatic clearance and predict changes in the disposition of substrates when homeostasis of the organ is perturbed. Their ability to describe metabolism was presently extended to the sequential formation and elimination of primary (M1), secondary (M2), and tertiary (M3) metabolites during a single passage of drug (P) across the liver, under steady state and first-order conditions. The well-stirred model is distinct from other models in that metabolite formation and elimination is independent of enzymic distributions, the number of steps involved in metabolite formation, and the intrinsic clearances of the precursors. This model predicts that the extraction ratio of a formed primary metabolite derived from drug (E[M1, P]) is identical to that for the preformed primary metabolite (E[M1]), and that the extraction ratios of a secondary metabolite derived from drug (E[M2, P]) and primary metabolite (E[M2, M1]) or preformed secondary metabolite (E[M2]) are identical. For the more physiologically acceptable, parallel-tube and dispersion models, metabolite sequential elimination is highly influenced by the intrinsic clearances of the precursors and the enzymic distributions that mediate removal of precursor species and the metabolites. Furthermore, the extent of sequential metabolism recedes as the number of steps involved for metabolite formation increases. These models predict that E[M1, P] less than E[M1], and E[M2, P] less than E[M2, M1] less than E[M2], with the magnitude of the changes being less for the dispersion model than for the parallel-tube model. Competing pathways that divert substrate from entering the sequential pathway were found to exert only minimal influence on the sequential pathway. PMID- 1629795 TI - Application of the axial dispersion model of hepatic drug elimination to the kinetics of diazepam in the isolated perfused rat liver. AB - The application of the axial dispersion model to diazepam hepatic elimination was evaluated using data obtained for several conditions using the single-pass isolated perfused rat liver preparation. The influence of alterations in the fraction unbound in perfusate (fu) and perfusate flow (Q) on the availability (F) of diazepam was studied under steady conditions (n = 4 in each case). Changes in fu were produced by altering the concentration of human serum albumin (HSA) in the perfusion medium while maintaining diazepam concentration at 1 mg L-1. In the absence of protein (fu = 1), diazepam availability was 0.011 +/- 0.005 (mean +/- SD). As fu decreased, availability progressively increased and at a HSA concentration of 2% (g/100 ml), when fu was 0.023, diazepam availability was 0.851 +/- 0.011. Application of the axial dispersion model to the relationship between fu and F provided estimates for the dispersion number (DN) of 0.337 +/- 0.197, and intrinsic clearance (CL(int)) of 132 +/- 34 ml min-1. The availability of diazepam during perfusion with protein-free media was also studied at three different flow rates (15, 22.5, and 30 ml min-1). Diazepam availability always progressively increased as perfusate flow increased, with the axial dispersion model yielding estimates for DN of 0.393 +/- 0.128 and CL(int) of 144 +/- 38 ml min-1. The transient form of the two-compartment dispersion model was also applied to the output concentration versus time profile of diazepam after bolus input of a radiolabeled tracer into the hepatic portal vein (n = 4), providing DN and CL(int) estimates of 0.251 +/- 0.093 and 135 +/- 59 ml min-1, respectively. Hence, all methods provided similar estimates for DN and CL(int). Furthermore, the magnitude of DN is similar to that determined for noneliminated substances such as erythrocytes, albumin, sucrose, and water. These findings suggest that the dispersion of diazepam in the perfused rat liver is determined primarily by the architecture of the hepatic microvasculature. PMID- 1629797 TI - Proceedings of the scientific meetings of The Physiological Society. December 1991 thru April 1992. Abstracts. PMID- 1629796 TI - Effect of angiotensin II-induced changes in perfusion flow rate on chlorothiazide transport in the isolated perfused rat kidney. AB - Angiotensin II was used as a probe to study the effect of changes in perfusate flow rate on the renal clearance parameters of chlorothiazide in the isolated perfused rat kidney. Perfusion studies were performed in five rats with no angiotensin II present in the perfusate and in five rats with a 1-4 ng/min infusion of angiotensin II into the perfusate. Angiotensin II had a dramatic effect on the renal hemodynamics, resulting in a 43% decrease in perfusate flow, a 16% decrease in glomerular filtration rate (GFR), and a 45% increase in filtration fraction. Values for the fractional excretion of glucose were low and consistent, with or without angiotensin II. Although the unbound fraction (fu) of chlorothiazide was unchanged between treatments, the renal (CLr) and the secretion clearances were reduced by about 50% in the presence of angiotensin II; the excretion ratio [ER = CLr/(fu.GFR)] was reduced by 38% with angiotensin II present in the perfusate. Analysis of the data was complicated by the presence of a capacity-limited transport for renal tubular secretion. Transport parameters (+/- SD) were obtained and the corrected intrinsic secretory clearance [(Vmax/GFR)/Km] of chlorothiazide was 123 +/- 18 without angiotensin II vs. 72.8 +/- 30.0 with angiotensin II. These results demonstrate that alterations in organ perfusion can significantly reduce the clearance parameters of chlorothiazide in the rat IPK. These flow-induced changes in intrinsic secretory transport may reflect perturbations other than that of perfusion flow rate alone. PMID- 1629798 TI - Staged major limb replantation: a concept to minimize the risk in replantation of the lower extremity. AB - The replantation of large limb segments presents two major problems: first, a general danger to survival because of major accompanying injuries and additional ischemia-reperfusion injury; second, local soft-tissue damage at the amputation site. Successful replantation can be compromised by infection, vessel thrombosis, and disturbed bone healing. Possible risk reduction may be accomplished by the concept of a two-staged replantation. A brief primary emergency procedure involving bone resection, osteosynthesis, and revascularization (with the goal of limb survival) is followed by a second procedure within 72 hr after trauma, for final debridement, completing the osteosynthesis, nerve and tendon suturing, and soft-tissue coverage by free flaps. The advantages of the double procedure are demonstrated in 27 patients by comparison of two treatment groups. Group I comprised 15 patients with definitive primary care. In Group 2 (n = 12), the two stage operation was performed. The second group showed a shorter duration of overall treatment, reduction of blood loss, and fewer infections. PMID- 1629799 TI - Vascular resistance considerations in free-tissue transfer. AB - The closure of complex wounds is facilitated by microvascular free-tissue transfer. The greatest threat to the success of a free-tissue transfer is thrombosis of the microvascular anastomosis. Technical and pharmacologic advances have decreased the thrombogenic effect of abnormalities of a vessel's endothelial lining, and have decreased the coagulation ability of blood. Equally important to patency of the microvascular anastomosis is blood flow, which is inversely proportional to the total resistance provided by the microcirculatory beds downstream. Because different tissues possess different vascular resistances, some flaps may display more favorable hemodynamics than others. This study was designed to characterize vascular resistance, weight, volume, and surface area of the flaps available for transfer, and to identify favorable tissues for reconstruction from the standpoint of outflow resistances. Data were collected on patients undergoing free-tissue transfers and on experimental free-tissue transfers harvested from canines and fresh cadavers. Results show that resistance is highest in fascial flaps, intermediate in composite bone and soft-tissue flaps, and lowest in muscle and musculocutaneous tissues. Resistance is lower in flaps harvested from the trunk, compared with those harvested from the extremities. The rate of microvascular complications increases as resistance within the flap increases. Muscle and musculocutaneous flaps harvested from the trunk have lower complication rates than fascial and fasciocutaneous flaps. Suggestions for choices of flaps are made, based on the inherent resistance in the various free flap tissues. PMID- 1629800 TI - Functional limb salvage combining gastrocnemius neurotization and posterior tibial nerve grafting: a case report. AB - Functional limb salvage requires motor and sensory reconstruction of the extremity. An avulsion of the tibial nerve in the popliteal fossa after arthroscopy is presented. Functional limb recovery necessitated intraoperative nerve mapping by awake stimulation, neurotization of the gastrocnemius muscle bellies, and interfascicular posterior tibial nerve grafting. Eighteen-month follow-up demonstrated good gastrocnemius motor function and protective sensation on the plantar surface. The patient is ambulatory without the need of an assistive device. PMID- 1629801 TI - The osteocutaneous fibula flap: an anatomic study. AB - Recent studies related to the fibula flap have disagreed regarding the anatomy of the cutaneous branches of the peroneal artery. To clarify this issue, various dissections of 35 injected fresh cadaver legs were done. Identifiable skin branches were found in 23 of 25 dissections. Skin branches from the proximal third of the peroneal artery always travelled an intramuscular course. Skin branches from the distal two-thirds of the peroneal artery were usually affixed to the posterior crural septum. Legs with peroneal artery skin branches had from three to seven branches (average: 4.7); each branch contributed to the fibular periosteal blood supply. The most reliably found skin branch was located within 2 cm of the fibula midpoint. These findings reinforce the fact that a large skin island supplied by branches of the peroneal artery can be harvested with the fibula flap, and that the most reliable cutaneous vessels are found in the lower two-thirds of the leg, run posterior to the fibula in the posterior crural septum, and are always associated with muscular side branches. PMID- 1629802 TI - Phalloplasty techniques. PMID- 1629803 TI - The turbo gracilis myocutaneous flap. AB - While the gracilis muscle flap continues to be used for coverage of selected defects and in specialized applications such as facial reanimation, the lack of reliability of the distal skin component of the gracilis musculocutaneous flap has limited its usefulness. Reliable distal skin and muscle viability are particularly important when the gracilis musculocutaneous free flap is used in forearm flexorplasty. A method for "turbo-charging" this flap, to improve distal reliability, is described. The anatomy of 24 human lower extremities was studied, with respect to the arterial supply to the distal gracilis muscle and distal medial thigh skin. A consistent septal branch, originating from the superficial femoral artery proximal to the adductor canal, supplying the distal gracilis muscle as well as the overlying skin, was identified in all extremities. "Turbo charging" via this vessel increases the reliability of both the distal skin island and distal muscle of the gracilis myocutaneous flap and enhances its versatility, when used as either a pedicle or free flap. PMID- 1629804 TI - Peripheral arteriovenous anastomosis: an alternative technique in a free flap transfer. AB - Prevention of thrombosis in the inflow and outflow vessels of a free flap is a problem of current interest. The method of creating a peripheral arteriovenous anastomosis within a free flap was validated in an experimental study and substantiated in a clinical case. No thrombotic complications were observed in 16 transfers of saphenous fasciocutaneous flaps in a dog model, as well as in an elderly patient with free radial forearm flap transfer to an irradiated foot. Scanning electron microscopy of the venous anastomosis proximal to the arteriovenous fistula revealed the difference of pathologic changes as early as 4 hr following surgery. It is the conclusion of the authors, that performing a distal arteriovenous fistula in a free flap, is an effective procedure for prevention of early occlusion in a proximally anastomosed artery and vein. PMID- 1629805 TI - Reconstruction of the bones and joints of the upper extremity by vascularized free fibular graft: report of 46 cases. AB - The vascularized free fibular graft was applied in reconstructing bone and joint structures of the upper extremity in 46 cases between August, 1977 and December, 1989. Among these, 30 were grafts of the fibular shaft and 16 were grafts of the fibular head. There were 19 bony defects after trauma or osteomyelitis, 18 bony or articular defects after resection of tumors, five congenital deformities or defects, and four replacements for fibrous dysplasia. The longest grafted fibula was 22 cm and the shortest, 5 cm. Thirty-one cases were followed for more than two years, and these were evaluated for functional ability in daily living, roentgenologic appearance, and 99mTc scan during follow-up. The results revealed quite sufficient functional restoration, solid bone healing, and adequate blood supply, in most cases. The vascularized free fibular head graft appears to be an ideal procedure for the reconstruction of defects of the lower end of the radius or the upper humerus, including the humeral head. The stability of the reconstructed wrist or shoulder joint was maintained by suturing the lateral collateral ligament, the palmar collateral ligament around the wrist, or by passing the long head of the biceps brachii through the grafted fibula at the shoulder. Methods for fixation of the fibular shaft to the recipient bone and the selection of vessels for anastomoses, both in the graft and at the recipient site, are discussed. The importance of postoperative functional exercise is emphasized. PMID- 1629806 TI - CO2 laser-assisted repair of esophageal lacerations. AB - This study was designed to evaluate the feasibility of CO2 laser-assisted repair of esophageal injuries. Nine-millimeter longitudinal incisions were made in the cervical esophagus of 40 Sprague-Dawley rats. The rats were divided into two groups. Twenty rats in Group 1 had their incisions closed in two layers (mucosa and muscularis) with the I.L. Med Unilase microsurgical CO2 laser (LAREL), using 80 mW of power with a spot size of 200 mu (power density = 255). Twenty rats in Group 2 had their incisions closed in two layers using 8-0 Vicryl conventional suture technique (CST). Postoperatively, an intraluminal methylene blue injection evaluated patency and leakage. Histologic analysis was performed at 3 days, 2 weeks, 1 month, and 6 months. Patency rates of LAREL and CST were comparable. No fistulas or strictures were found with either technique. Laser-assisted repair of esophageal lacerations (LAREL) was found to be faster and easier than CST. The question arises whether small esophageal tears can be safely repaired through the endoscope. This study demonstrates the feasibility of tissue welding the esophagus. Further research is mandatory to study the applicability of this technique in the clinical setting. PMID- 1629807 TI - An experimental study of the flow-through venous flap: investigation of the width and area of survival with one flow-through vein preserved. AB - A quantitative analysis was undertaken to investigate the width and area of survival of flow-through venous flaps in 20 ears of 10 rabbits. The 3.0- x 3.0-cm flap models, which included one flow-through vein, were prepared with additional circulation from the graft bed and surrounding tissue excluded, as far as possible. The flaps were divided as follows: Group A--composite grafts (n = 10), and Group B--flow-through venous flaps (n = 10). All flaps in Group A became necrotic and all those in Group B showed partial survival along the flow-through vein. The average survival width was 1.10 +/- 0.48 cm, and the survival rate was 44 +/- 19.3 percent. Microangiograms revealed patency of the flow-through vein in all flaps of Group B. Histologically, there tended to be progressively more fibrous tissue in the area further away from the flow-through vein. The model is useful to investigate the width and area of survival in flow-through venous flaps. PMID- 1629808 TI - Reversing nerve-graft polarity in a rat model: the effect on function. AB - To evaluate the effect of nerve-graft polarity on function, a 1-cm segment of sciatic nerve was excised and reoriented in three groups of 20 adult Sprague Dawley rats. In one group, the nerve was cut and anastomosed in the original orientation to act as a control. In the second group, the nerve-graft polarity was reversed 180 degrees. The final group underwent reversal of polarity 180 degrees and was rotated 180 degrees, (i.e., the posterior tibial nerve fascicles proximally were opposite to the peroneal nerve fascicles distally). Functional recovery was evaluated using Bain's modification of de Medinaceli's sciatic functional index (SFI). Rat-track analysis was performed over a 120-day period. Histologic correlation was also performed at the time of sacrifice. From our study, we concluded that reversing nerve-graft polarity, with or without rotation, does not influence subsequent function in this model. PMID- 1629809 TI - Transient single-digit ectopic implantation. AB - Although immediate replantation of an amputated digit is always preferable, mitigating circumstances (such as a severe concomitant injury involving the appropriate recipient neurovascular structures) might preclude such an attempt altogether. However, if these local structures have the potential, following adequate debridement and/or other tissue transfer, to accept this digit later, than an alternative for transient storage for delayed replantation should be considered. The deep inferior epigastric vessels are a recognized convenient site that could provide temporary ectopic revascularization of such a solitary finger. An example of this approach for thumb preservation is presented, although amputation of the hand before performing the secondary transfer unfortunately proved prudent. PMID- 1629810 TI - Pathology of the shoulder as it relates to the differential diagnosis of thoracic outlet compression. AB - Shoulder pathology and its diagnosis must be considered in evaluation of the patient suspected of having thoracic outlet syndrome (TOS). Overlooking usually treatable conditions in the shoulder may lead to unfavorable results, if treatment is directed, instead, to neurolysis of the brachial plexus or first rib resection. PMID- 1629811 TI - Blood-flow measurements of injured peripheral nerves by laser Doppler flowmetry. AB - The effects of injury on peripheral nerve blood flow were studied, using a Laserflo blood perfusion monitor. A total of 11 nerves were studied, five normal and six injured nerves in four patients. Two of the patients had lacerating brachial plexus injuries, and two other patients had compressive neuropathies of their ulnar nerves at the elbow. All of the readings were taken intraoperatively while the patients were undergoing exploration and repair under general anesthesia. Measurements of the damaged nerves were taken serially from the site of injury proximally and distally, by approximating a flexible metric ruler to the dorsal aspect of the nerve along the same axis. In the acutely lacerated injured nerves (3 to 7 days), the measurements were taken at 1, 5, 10, and 20 mm. The maximal amount of retraction in any of the nerves was 1 cm; thus, the overall architecture of the nerves was maintained. In the compressed nerves, measurements were taken at 1, 2 and 3 cm proximal and distal to the medial epicondyle. Measurement of normal undamaged nerves was performed at six different sites along the same axis of the nerve. The averaged results indicate that the normal blood flow ranged from 47 ml/100 g/min to 63 ml/100 g/min, with a mean of 56 ml/100 g/min. In the injured nerves, blood flow was most depressed at sites closest to the laceration, and increased consistently and progressively at sites distant from the injury in both directions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629812 TI - Pre-formed vascularized bone grafts using polyethelyne chambers. AB - Previous work has shown that corticocancellous bone chips placed in a titanium chamber with an arteriovenous vascular pedicle will result in a pre-formed vascularized bone graft. The present study was designed to determine whether these grafts can be transferred as an island or free vascularized bone graft, and to examine the material properties of these grafts. Thirty-two male, New Zealand white rabbits were divided into four groups based on the time of sacrifice following the initial chamber implantation. Injected molded cylindrical polyethelyne chambers, measuring 22 mm long and with an 8-mm inner diameter, were used. Corticocancellous bone chips were placed in the chambers and each chamber was implanted in the mid-thigh, with saphenous vessels running through the chamber. The chambers were implanted into the right and left thigh of each animal. To test the hypothesis of the possibility of transferring this graft as an island or free vascularized graft, ligation of the distal vascular pedicle on one side was achieved at re-exploration at 3, 6, 9, and 12 weeks. The contralateral side served as a control in which the vascular pedicle was not ligated. In the controls, bony bridging between the corticocancellous bone chips was observed after 7 weeks. A solid bone graft was present within the chamber by 10 weeks. However, histomorphometric evaluation indicated significant bone resorption. By 13 weeks, resorption progressed to the point where only small islands of bone remained. Ligation of the distal vessels resulted in thrombosis of the vessels within the chamber. Necrosis of newly-formed bone was observed in the area adjacent to the vascular thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629813 TI - Priority in the use of the forearm free flap in one-stage phalloplasty. PMID- 1629815 TI - Classification criteria--what value do they serve? PMID- 1629814 TI - Liver biopsies in patients with rheumatoid arthritis receiving methotrexate: where are we going? PMID- 1629816 TI - Rheumatology on the dark continent: not as dark as it was. PMID- 1629817 TI - Comparison of the sensitivity and specificity of the 1958 and 1987 criteria for rheumatoid arthritis. AB - The 2 variations of the new criteria for rheumatoid arthritis (RA) proposed by a subcommittee of the American College of Rheumatology (ACR) in 1987 were evaluated and compared with the earlier (1958) criteria in 2 patients data collections from a Dutch rheumatological outpatient clinic. One group comprised 1,570 newly referred, consecutive patients, including 93 patients with RA. The other consisted of 1,338 patients with a clinical diagnosis of RA, whose charts were reviewed retrospectively. The sensitivities of the 2 variations of the 1987 criteria in the prospective and retrospective subgroups varied from 66 to 89%; those of the 1958 set, from 71 to 86%. Specificity was 98% for both criteria sets. Comparison in subgroups with different disease durations showed reduction in sensitivity for early RA for either variation of the new criteria. However, the differences between the results of the 1958 and 1987 criteria sets are small enough to conclude that they perform equally well. PMID- 1629818 TI - Protective effects of ciprofloxacin against type II collagen induced arthritis in rats. AB - Ciprofloxacin, a new fluoroquinolone antibiotic, inhibits the in vitro production of interleukin 1 beta and tumor necrosis factor alpha by monocytes. We investigated its activity against type II collagen induced arthritis in rats. It exerted a dose dependent preventive effect at 50 and 75 mg/kg/day against clinical and histologic features of collagen induced arthritis without any influence on the production of anticollagen antibodies and alpha 1-acid glycoprotein. This effect was reversible after early removal of the treatment. Ciprofloxacin did not inhibit collagen induced arthritis in adrenalectomized rats but rather caused an exacerbation of the disease. Its effect was not modified by the simultaneous administration of an antiglucocorticoid, RU 40555. PMID- 1629819 TI - Clinical liver disease in patients with rheumatoid arthritis taking methotrexate. AB - Between 1981 and 1989, 3 of 134 patients with rheumatoid arthritis (RA) treated with methotrexate (MTX) developed clinically significant hepatic dysfunction and showed histologic evidence of severe liver disease (fibrosis and cirrhosis). Factors identified in these patients that may have been linked to liver toxicity included diabetes, congestive heart failure and Felty's syndrome. In the patient group that received a post-MTX liver biopsy, pulmonary fibrosis and obesity were significantly associated with hepatic fibrosis/cirrhosis. Severe liver disease may occur in patients with RA treated with low dose MTX (less than 3%). Early liver biopsy is recommended in selected cases. PMID- 1629820 TI - Genetic studies of anti-Ro (SSA) antibodies in families with rheumatoid arthritis. AB - Forty-nine members of 4 families with multiple cases of rheumatoid arthritis (RA) were investigated. Nine patients with RA, one patient with primary Sjogren's syndrome (SS) and one patient with systemic lupus erythematosus (SLE) were detected among them. Anti-Ro (SSA) antibodies were found in 11 members (22%) of the investigated group; 6 suffered from RA, SLE or primary SS, and 5 were healthy first degree relatives. Anti-La (SSB) antibodies were detected in only one family member with primary SS. Secondary SS was evident in 5 patients with RA, 3 of whom had anti-Ro antibodies; HLA-DR4 was present in 7 of 9 patients with RA (78%) but in only 7 of 26 asymptomatic relatives (27%) (p less than 0.05). All patients with RA and their relatives who had anti-Ro antibodies were found to have HLA DR4. Our results demonstrate that anti-Ro antibodies are present in relatives of patients with RA and are strongly associated with HLA-DR4. PMID- 1629821 TI - What factors distinguish probands from multicase rheumatoid arthritis same sex sibships from sporadic disease? AB - Thirty-two of 243 same sex sibships in which the proband had rheumatoid arthritis (RA) had at least one same sex sibling with RA ("familial" RA) and 211 did not ("sporadic" RA). The most important factors accounting for familial RA were the sibship size, and the proportion of siblings sharing both HLA haplotypes with the proband. Demographic and clinical details, autoantibodies and HLA-DR status were similar between the 2 groups, with the exceptions of regular use of artificial teardrops, and involvement of distal interphalangeal joints, which were both more prevalent in familial RA. The extrapolation of results from familial to sporadic RA appears to be justified. PMID- 1629822 TI - Extraarticular manifestations of rheumatoid arthritis and HLA antigens in northern Italy. AB - We performed retrospective analysis of 141 Northern Italian patients with rheumatoid arthritis (RA). This series represents all the patients seen as in and/or outpatients at the rheumatologic unit of Reggio Emilia Hospital during a 2 year period (1987-88). We observed a low frequency of nodules (16%) and vasculitis (2.1%). Thus, RA seems to be milder in our population compared to Caucasian patients with RA originating from North America or England. We observed a weak association with DR4 (RR = 2.4) in the total group of patients with RA. A low frequency of DR4 was observed in patients and controls (29 vs 14.5%, p = 0.001). When compared with controls the frequency of DR4 was significantly higher in seropositive (p = 0.001), but not in seronegative patients. We found that DR4 was significantly associated with nodules (RR = 6.4), with extraarticular features (EAF) (RR = 4) and with erosions (RR = 3) compared with controls. The subgroups with nodules and EAF had a DR4 frequency (respectively, of 52 and 40%) which was significantly higher than that observed in remaining patients (respectively, 25 and 24%). No significant difference was observed in the DR4 frequency between the patients with erosions and those without (34 vs 18%). Thus, DR4 in our population seems to be predominantly associated with a subgroup of patients characterized by seropositivity and EAF. PMID- 1629823 TI - High dose intravenous methotrexate for refractory rheumatoid arthritis. AB - Eight patients with active rheumatoid arthritis were given high dose intravenous methotrexate (MTX) (500 mg/m2) followed by oral leucovorin every 2 weeks for up to 6 months. All patients enrolled had previously failed conventional MTX therapy. Five patients completed 6 months of therapy. Three withdrew early, one due to inefficacy, one due to gastrointestinal intolerance and one due to sciatica requiring hospital admission. Fifty percent or greater improvements were seen in 5 of 8 clinical variables in those patients who completed 6 months of therapy. Six of 8 improvements achieved statistical significance at 24 weeks. Upon discontinuing therapy, patients flared within 8 to 12 weeks. Those who were maintained by low dose MTX after the high dose protocol were able to sustain their improvement throughout the subsequent 6 months of followup. PMID- 1629824 TI - Japanese diagnostic criteria for mixed connective tissue disease in Caucasian patients. AB - Preliminary Japanese diagnostic criteria for the classification of mixed connective tissue disease (MCTD) were tested in a group of 32 Caucasian patients with this disease. Many clinical and laboratory similarities were found between Caucasian and Japanese patients. However, polyarthritis was more frequent in the Caucasians, while finger and hand swelling, DLCO reduction and muscle involvement were more frequent in the Japanese. In Caucasians the sensitivity of this criteria set was 87%, very similar to that found in the Japanese group (88%), and the specificity was 94%, higher than that of Japanese (87%). The difference resulted from the higher specificity of anti-nRNP antibody positivity in the Caucasian patients, probably due to the use of counterimmunoelectrophoresis in the detection of this antibody. The Japanese criteria seem more useful than others because they allow the use of techniques other than passive hemagglutination in detecting the anti-nRNP antibody. In our experience, such criteria also contribute to a better definition of MCTD in Caucasian patients. PMID- 1629825 TI - Antibiotic allergy in systemic lupus erythematosus: a case-control study. AB - Antibiotic allergy, especially to sulfonamides, has been reported as both a predisposing factor and as an exacerbating agent in systemic lupus erythematosus (SLE). We surveyed 221 members of The Johns Hopkins Lupus Cohort and 2 control groups, consisting of 178 relatives and 186 best friends, for antibiotic allergy to penicillin/cephalosporins, sulfonamides, tetracyclines, and erythromycin. Antibiotic allergy was common in patients with SLE exposed to the drug: 27% penicillin/cephalosporin, 31% sulfonamide, 7% tetracycline, and 13% erythromycin. In all cases, the most common allergic reaction was rash. Worsening of SLE occurred in 21% of sulfonamide allergic reactions. Allergy to penicillin/cephalosporin (OR 2.3, 95% CI 1.5-3.6), sulfonamides (OR 2.4, 95% CI 1.2-4.7) and to erythromycin (OR 4.8, 95% CI 1.5-14.9) was significantly more common in exposed patients with SLE than in exposed controls. Thus, antibiotic allergy is a frequent finding in patients with SLE and, in the case of sulfonamide allergy, can be associated with lupus exacerbation. PMID- 1629826 TI - Polymyalgia rheumatica and seronegative rheumatoid arthritis may be the same entity. AB - Of 159 patients with either polymyalgia rheumatica, seronegative rheumatoid arthritis (RA) or an undifferentiated syndrome with features of both who were followed for at least 30 months, synovitis recurred in 57. Twenty of the 57 patients had one episode of polymyalgia and another that looked like RA. Recurrences responded to prednisone and no joint destruction was seen. Temporal arteritis was seen with both diagnoses. These observations suggest that a benign symmetric synovitis occurs in older patients and may present as polymyalgia or as a polyarthritis that resembles RA. PMID- 1629827 TI - Giant cell arteritis and polymyalgia rheumatica in a region of Finland: an epidemiologic, clinical and pathologic study, 1984-1988. AB - The occurrence of giant cell arteritis (GCA) (considering temporal arteritis and polymyalgia rheumatica as its manifestations) was investigated in Western Nyland, Finland. Between 1984 and 1988 54 patients were diagnosed in a population of about 44,500. Fourteen patients (26%) had biopsy proven arteritis at the initial evaluation, and 2 patients became biopsy positive during followup. The retrospectively determined annual incidence of GCA in a 44 month period was 22.5/10(5) in the whole population, and 69.8/10(5) in residents aged 50 years or older. The corresponding figures of a prospective 16 month study were 30.4/10(5) and 94.4/10(5). The incidence rates of the prospective study are higher than those reported in comparable studies. Polymyalgia rheumatica, occurring alone or combined with cranial symptoms, was the most frequent manifestation of GCA, being present in 87% of patients. PMID- 1629828 TI - Temporal arteritis in a northwestern area of Spain: study of 57 biopsy proven patients. AB - Fifty-seven patients, diagnosed with temporal arteritis by biopsy from 1981 to 1990, were studied. The average annual incidence rate/100,000 population aged 50 and older, which was slightly lower than those from other Mediterranean countries of Europe, was 6. Apart from a predominance of males, age, clinical and laboratory features were similar to those reported from other parts of the world. All patients received corticosteroid therapy, the majority of them recovered completely. Fifty-four were followed; 34 had already finished treatment (mean: 22 months, range: 12-50). Relapses occurred more commonly after 12 months of therapy, when the amount of prednisone given was low or discontinued. PMID- 1629829 TI - Peripheral arthralgic presentation of fibrositis/fibromyalgia syndrome. AB - Of 216 consecutive new referrals to a general rheumatology clinic 22 (10.2%) had generalized fibromyalgia syndrome (FS). In 12 cases (5.6% of all referrals, 54.5% of patients with FS) the initial presentation was with pain in the region of the hand or wrist joints, but many other joints were painful or tender. Although there may be initial confusion with rheumatoid or osteoarthritis, the positive features of FS confirm the correct diagnosis. PMID- 1629831 TI - International symposium on psoriatic arthritis. PMID- 1629830 TI - Relation between fibrositic and control site tenderness; effects of dolorimeter scale length and footplate size. AB - Recent data have suggested a correlation between the tenderness measured at tender and control sites, differing from earlier studies indicating site specific tenderness. In our study, the "constant control" model is tested against the "correlated control" model, in which control site tenderness varies with fibrositic site tenderness. Our study also addresses relevant technical issues in dolorimetry. We measured threshold of tenderness at 4 sites (2 fibrositic and 2 control) on 21 subjects, using dolorimeters with a 17 kg scale limit, and 3 different footplates, 0.7, 1.4 and 2.0 cm in diameter. To measure observer variation, we used multiple replications by multiple observers, obtaining in all 1,416 observations. There was a strong relationship between control and fibrositic site tenderness with control thresholds twice as high (half as tender). Scale length and dolorimeter footplate size each had important effects. The site specific approach is valuable diagnostically, but more broadly operative mechanisms should be the focus of research and therapy. PMID- 1629832 TI - Influence of pregnancy on disease activity in a patient with palindromic rheumatism. AB - A 30-year-old woman with a 12-year history of palindromic rheumatism without progression to chronic arthritis experienced pronounced reduction of arthritic symptoms during both of her 2 pregnancies with, on each occasion, symptoms recurring 3 months after delivery. This is the first reported case suggesting an ameliorating effect of pregnancy on disease activity in palindromic rheumatism. PMID- 1629833 TI - Transient myopia with severe chemosis associated with exacerbation of disease activity in systemic lupus erythematosus. AB - A 46-year-old woman with systemic lupus erythematosus (SLE) developed bilateral transient myopia and periorbital edema with severe chemosis. Her myopia was ascribed to a refractive abnormality that was caused by curvature change and anterior displacement of the lenses and the ciliary bodies due to anterior ocular edema. The conditions were not associated with systemic edema or abnormality in the fundi and responded well to the systemic administration of corticosteroid. The course of the ocular symptoms paralleled changes of serum CH50 and anti-dsDNA antibody levels. Thus it was concluded that her ocular symptoms were closely related to activity of her SLE and may be considered a feature of SLE. PMID- 1629834 TI - Inclusion body myositis in association with vitamin B12 deficiency and Sjogren's syndrome. AB - Autoimmune disorders are very rarely associated with inclusion body myositis (IBM). We describe a patient with IBM in association with Sjogren's syndrome (SS) and Vitamin B12 deficiency. B12 deficiency has not been reported in SS, and this deficiency may explain the neuropathic features of some patients with IBM. PMID- 1629835 TI - Trichinosis with severe myopathic involvement mimicking polymyositis. Report of a family outbreak. AB - We describe an outbreak of trichinosis in 3 members of a rural family. In the 3 patients eating raw pork was the source of infection. They presented with myalgias and severe proximal muscle weakness mimicking polymyositis. The diagnosis was made by demonstration of larvae of Trichinella spiralis in the muscle biopsy and also by the presence of anti-Trichinella antibodies detected by double immunodiffusion in their sera. We call attention to the unusual clinical presentation of trichinosis in our patients that was manifested by severe muscle weakness that may be confused with polymyositis. PMID- 1629836 TI - Chronic syphilitic polyarthritis mimicking systemic lupus erythematosus/rheumatoid arthritis as the initial presentation of human immunodeficiency virus infection. AB - Syphilitic arthritis has been well characterized but not previously described as the initial presentation of human immunodeficiency virus (HIV) infection. Our patient presented with chronic symmetric polyarthritis and autoimmune abnormalities, including positive rheumatoid factor, antinuclear antibody, dsDNA, and initially negative syphilis serologies. Subsequent investigations revealed HIV seropositivity, depletion of CD4 cells, and strongly positive syphilis serologies. Our patient's arthritis completely resolved with penicillin therapy. PMID- 1629837 TI - Human T lymphotropic virus I, myelopathy, polymyositis and synovitis: an expanding rheumatic spectrum. AB - A black woman developed chronic myelopathy, polymyositis and synovitis. Although native of a nonendemic area the possibility of human T lymphotropic virus I association was considered. She tested positive and was serendipitously found to have been positive 16 years before. Risk factors were a transfusion and work as a serology technician. Sjogren's syndrome, alveolitis, gammopathy and immune dysfunction are other rheumatic manifestations of this virus. PMID- 1629838 TI - Pigmented villonodular synovitis presenting as a subcutaneous mass at the knee. AB - We describe a 45-year-old man who developed a painful mass about his knee. Magnetic resonance imaging demonstrated a well defined lesion, and biopsy confirmed a diagnosis of pigmented villonodular synovitis. Our case exemplifies a primary synovial process presenting as a subcutaneous tumor. Such diagnostic possibilities, although rare, should be more widely known. PMID- 1629839 TI - Close temporal and anatomic relationship between multicentric reticulohistiocytosis and carcinoma of the breast. AB - We describe a case of simultaneous development of a medullary carcinoma of the breast and multicentric reticulohistiocytosis (MRH) with identical characteristic histological lesions being found not only in the skin and synovium, but also in close proximity to the breast cancer as well as the connective tissue surrounding the tumor involved axillary lymph nodes. Successful treatment of the primary malignancy resulted in complete resolution of the MRH over 4 months. A close temporal relationship existed between the development and clinical remission of the malignancy and the course of the arthritis and skin lesions. Characteristics of this rare syndrome with particular reference to its association with malignancy are reviewed. PMID- 1629840 TI - Staphylococcus lugdunensis arthritis: a complication of arthroscopy. PMID- 1629841 TI - Favorable outcome with ketoconazole in Candida septic arthritis. PMID- 1629843 TI - Complications of hormone replacement therapy in post-menopausal women. PMID- 1629842 TI - Pathogenesis of multiple sclerosis. PMID- 1629844 TI - The one-tool technician. PMID- 1629845 TI - Magic and mountebanks in the development of psychiatric thought. PMID- 1629846 TI - Urinary incontinence among patients with arthritis--a neglected disability. AB - Urinary tract pathology may be no more common in patients with arthritis than among the general population, but its impact may be enhanced by disability. In this survey of 247 patients, as many as 38% of patients with rheumatoid arthritis (RA), 47% of patients with osteoarthritis (OA) and even 34% of patients with soft tissue rheumatism (STR) reported difficulty controlling their urine, confirming that incontinence is a widespread and often under-reported problem. More detailed enquiry in a sample of 90 patients with OA or RA did not suggest specific urinary tract pathology related to the underlying arthritis. Those who reported problems with urinary control were more disabled, and took longer to get to the toilet in their own environment than those without control problems. Twenty-seven per cent of patients felt that their problems would be solved by provision of a downstairs toilet. Timing of tasks performed by patients within their home is suggested as a method for assessing functional ability which encompasses both patient disability and environmental factors. PMID- 1629847 TI - Endometrioid carcinoma of the prostate: a misnomer? AB - The origin of this unusual variant of carcinoma of the prostate has provoked discussion ever since its first description in 1967. This is of both embryological interest and therapeutic importance. Four cases have been reviewed, and all have demonstrated immunohistochemical features consistent with an origin from prostatic tissue. In addition, three had evidence of disseminated disease which responded well to androgen ablation. It is concluded that the term endometrioid carcinoma is of descriptive value only, and these tumours are a variant of primary duct prostatic carcinoma. Patients should be treated by androgen ablation when metastases are present. PMID- 1629848 TI - Endometrial cells in the peritoneal cavity after laparoscopy and chromotubation. AB - The presence of endometrial cells in peritoneal fluid before and after laparoscopy and chromotubation was studied in 35 patients at different days of the menstrual cycle. Endometrial cells were found more frequently in peritoneal fluid samples taken in the second half of the menstrual cycle. PMID- 1629849 TI - Computerized assessment in neuropsychiatry using CANTAB: discussion paper. PMID- 1629850 TI - Computerized assessments of psychiatric disorder using PROQSY: discussion paper. PMID- 1629851 TI - Recombinant natural anticoagulants: a review. PMID- 1629852 TI - Benedict Duddell: pioneer oculist of the 18th century. PMID- 1629853 TI - Ancient neurilemmoma of the pelvis. PMID- 1629854 TI - Chronic adult T-cell leukaemia/lymphoma presenting with cutaneous manifestations. PMID- 1629855 TI - Ulcerative colitis and bleeding from a colonic vaginoplasty. PMID- 1629856 TI - Unusual telangiectasia in a nuclear veteran. PMID- 1629857 TI - 'Spontaneous' rectus sheath haematoma: a rare cause of abdominal pain. PMID- 1629858 TI - Compression screw migration with the sliding hip screw. PMID- 1629859 TI - Drug treatment of emotionalism following brain damage. PMID- 1629860 TI - Helicopters. PMID- 1629861 TI - Helicopters. PMID- 1629862 TI - Helicopters. PMID- 1629863 TI - Compensation for injury--re-appraisal. PMID- 1629864 TI - The centre thought to control sensory and motor activity in the early history of medicine. PMID- 1629865 TI - The centre thought to control sensory and motor activity in the early history of medicine. PMID- 1629866 TI - The strange case of Ms Elizabeth Trevers. PMID- 1629868 TI - Breastfeeding while HIV-infected. PMID- 1629867 TI - Renal artery embolism. PMID- 1629869 TI - Call to protect health workers. PMID- 1629870 TI - Freephone pollutants. PMID- 1629871 TI - Education and young people with inflammatory bowel disease. AB - Children and their parents are often anxious that chronic disease may interfere with examination performance. The provision within schools for children with inflammatory bowel disease (IBD) was investigated by a postal survey of headteachers of 98 schools with over 48,000 pupils in Leicestershire and Cardiff. Headteachers in Cardiff were more likely to have heard of ulcerative colitis (95%) than those in Leicestershire (70%), (X2 = 4.5, p less than 0.05). They knew of 16 children with inflammatory bowel disease. The majority of heads provide easy access to lavatories during examinations and would tell the examining body of a child's medical problem. While most heads would like more information about inflammatory bowel disease, few have facilities to inform teachers about chronic illness in young people. Most think healthy young people should be provided with information about chronic diseases, which they would like provided by nurses. Inflammatory bowel disease (IBD) affects over 1200 children in the United Kingdom. Children and their parents are concerned that these conditions will interfere with schooling, taking examinations and their employment (Rees et al 1983, Wyke et al 1988). Provisions by schools for children with IBD were investigated. PMID- 1629872 TI - Nutrient intakes of university women in Kuwait. AB - This study assessed the nutrient intakes of 203 female college students, aged 20 31 years, mean 21 years. Results from computer analysis of 3-day food records showed that, on the basis of group means, two thirds of Recommended Daily Allowance (RDAs) was met for all nutrients except iron, zinc, folacin and vitamin D. Nutrient intake and RDAs showed no significant differences related to marital status with the exception of vitamin D and manganese (p less than 0.05). The indexes of Nutritional Quality indicated that, on average, diets of the students met or exceeded nutrient density allowance for protein, vitamin A, vitamin C, thiamin, riboflavin, niacin, vitamin B6 and phosphorus. Nutrients for which the average female student consumption was below recommended standards on a calorie basis, were carbohydrates, fat, vitamin D, folacin, calcium, iron, zinc and sodium. The diets were limited in fibre, high in sugar, high in caffeine and slightly above recommendations in cholesterol. Female college students needed guidance in selecting nutrient dense foods. Attention in nutrition education programmes should be directed toward the individual student rather than the group. PMID- 1629873 TI - Water for thought!--Private water supplies and the consumer factor. AB - Individual supplies from non-mains water to private dwellings were studied in a local area of East Devon. Underground spring water piped from hilltop level to holding tanks, or gathered at ground level for household wells, was tested for bacterial contamination at its point of use. Purification methods if any, and their maintenance were observed. PMID- 1629874 TI - Contact between injecting drug users and general practitioners and its implications for health education. PMID- 1629875 TI - Gifted children. PMID- 1629876 TI - Stress, mental health and crime. PMID- 1629877 TI - 214 days on--has it worked for patients? PMID- 1629878 TI - Medicines, health and the fast of Ramadan. PMID- 1629879 TI - Some medical problems affecting the ethnic minorities of the UK. AB - As a result of numerous influences, some genetic and others environmental, disease patterns in many of the minor ethnic groups are often at variance with those affecting the long established indigenes of the United Kingdom. Also, several important infective conditions can be acquired during brief visits to the land of their birth, or of their ancestors. As integration into the life-style of the UK becomes increasingly established, several diseases of the 'westernised' or 'industrialised' nations are assuming a major importance in these groups. The last few decades have witnessed the arrival of so many diverse groups from nearly all parts of the world that an intimate and in-depth knowledge of these disease patterns is now essential to the pursuance of competent medical practice in the UK. PMID- 1629880 TI - Malcolm Morris Memorial Lecture:-AIDS in the 1990s: a global analysis. PMID- 1629881 TI - Public health in the United States. PMID- 1629883 TI - Meat inspection and the veterinary profession by Mr K Stewart. PMID- 1629882 TI - Management of migraine in adults by Dr E A MacGregor, February 1992. PMID- 1629884 TI - Effects of sympatho-adrenal activation on the finger microcirculation in mild hypertension. AB - Finger skin circulatory responses to three forms of sympatho-adrenal activation were investigated in 14 patients with mild hypertension and 14 matched normotensive controls. Finger nailfold skin capillary blood cell velocity was measured by video-photometric capillaroscopy and finger pulse volume by strain gauge plethysmography (digital arterial pulse amplitude; DAPA). DAPA decreased more markedly in the normotensive as compared with the hypertensive group during mental arithmetic stress (38 vs. 19%; P less than 0.05) and a cold pressor test (55 vs. 32%; P less than 0.05). Intravenous infusions of adrenaline (0.1-0.8 nmol/kg/min) decreased DAPA in normotensives but not in hypertensives (P less than 0.05). Capillary blood cell velocity was similar in the two groups at rest and decreased promptly and to a similar extent in both groups following mental arithmetic, adrenaline infusion and the cold pressor test (by approximately 60, 60 and 35%, respectively). It is concluded that mental stress and the cold pressor test induce instantaneous and marked effects on the skin circulation via neurogenic activation. The less marked effect on DAPA in the hypertensive group may reflect an elevation of basal vascular tone and/or early structural vascular changes in mild hypertension. The discrepancy between total finger and capillary circulatory responses to adrenaline may be attributable to different adrenoceptor populations and/or sensitivity in arteriovenous shunts, as compared with precapillary vessels. PMID- 1629885 TI - ACE inhibition improves insulin-sensitivity in aged insulin-resistant hypertensive patients. AB - We have compared the cardiovascular and metabolic responses to five different ACE inhibitors in 86 patients matched for age, body mass index, blood pressure, fasting plasma glucose and insulin levels in a placebo-controlled, double-blind, crossover, randomised trial. In the active drug treatment phase the patients were randomly assigned to one of five ACE inhibitors: captopril (75 mg/day; n = 16); enalapril (20 mg/day; n = 14); quinapril (20 mg/day; n = 17); ramipril (5 mg/day; n = 21) and lisinopril (20 mg/day; n = 18). Placebo and ACE inhibition phases lasted two weeks and were separated by a one week wash-out period. At the end of each treatment period blood pressure and heart rate were recorded and a fasting sample intravenous glucose tolerance test was conducted. Our study demonstrated that ACE inhibition significantly reduces blood pressure and improves insulin sensitivity. All the ACE inhibitors studied had similar cardiovascular responses but lisinopril displayed the larger metabolic response. PMID- 1629886 TI - Measurement of capillary cholesterol as an aid to the management of hypertensive patients with hyperlipidaemia--an assessment of the Reflotron. AB - The Reflotron dry chemistry method of capillary cholesterol measurement has been widely adopted as a rapid means of population screening. We attempted to use it to monitor changes in cholesterol in a trial of intensive dietary intervention in hyperlipidaemic hypertensives. Four hundred and eighty-nine capillary cholesterol levels measured by the Reflotron were compared with levels for venous samples obtained simultaneously and assayed by the Biochemistry Department using conventional laboratory methods. The mean difference between them was 0.3 mmol/l +/- 0.8 (SD). Approximately one-third of the variability in the difference between the two methods was explained by the variables, Reflotron machine used and time (R2 = 54%, adjusted R2 = 34%). We conclude that the Reflotron is not suitable for accurate assessment of the modest changes in cholesterol which occur in individual patients during dietary intervention. PMID- 1629887 TI - Comparison of office and serial automatic blood pressure readings in renovascular and essential hypertension. AB - Office blood pressures were compared with those obtained using a thirty minute recording with an automatic device (Dinamap) in thirty patients with essential hypertension and nineteen subjects with hypertension and renal artery stenosis. When matched for age and sex, no differences were found between both groups of patients with respect to their office or automatically recorded blood pressures. The difference between office and automatically assessed systolic blood pressures was similar in both groups. The difference in diastolic pressures was slightly larger in the group with renal artery stenosis. The number of patients showing a pressure drop greater than 10 mm Hg was comparable in the two groups. We conclude that blood pressure levels obtained in the office overestimate 'true' blood pressure not only in essential but also in renovascular hypertension. PMID- 1629888 TI - Analysis of factors related to hypertension in Japanese middle-aged male workers. AB - A total of 789 Japanese male transport service workers between the ages of 35 and 50 were used as subjects in an analysis of daily lifestyle factors related to hypertension. Multiple logistic analysis showed positive dose-response relations between hypertension and age, obesity and alcohol consumption. Age and obesity were factors having a linearly increasing odds ratios for hypertension (including borderline cases and those under treatment). Alcohol consumption of 56 g ethyl alcohol per day or more had an odds ratio about double that of those who did not drink. Smokers had 1/2 the odds ratio of non-smokers. Subjects working a 24-hr shift comprised mostly of standby duty showed a slightly lower rate of hypertension, but it was statistically insignificant. PMID- 1629889 TI - Correlates of blood pressure differ in high and in low plasma renin groups. AB - It has been proposed that the aetiology, pathophysiological status, and effective treatment of hypertensives depends on concomitant plasma renin levels. Epidemiological data are scarce on the interrelations of plasma renin activity (PRA), BP and correlates of BP in the general population. Therefore, profiles of BP correlates were compared between low PRA groups and high PRA groups in a relatively healthy population of 321 Chinese government employees working in the Taipei area, in the summer of 1987. The characteristics of the two PRA groups were similar in body mass index, urinary sodium, chloride, calcium excretion and fasting parathyroid hormone. However, the high PRA group was younger, smoked more, and had a higher mean urinary potassium excretion. Fasting plasma glucose, uric acid, and creatinine levels were lower in the low PRA group. Positive relationships between BP and urinary sodium, chloride, potassium, calcium, plasma cholesterol, triglyceride, and glucose, independent of age and body mass index, were demonstrated in the low PRA group, where a volume expansion state may exist. However, in the high PRA state, uric acid, haemoglobin concentration, insulin and parathyroid hormone level were correlated more closely with BP than in the low PRA state. Further studies are needed to examine whether the differing associations between BP and risk factors in the high and low PRA groups reflect different compensatory mechanisms or aetiological factors. PMID- 1629890 TI - First dose hypotension after captopril; can it be predicted? A study of 240 patients. AB - We have studied prospectively the acute blood pressure lowering effect on an oral dose of captopril, 25 mg in 240 hypertensive patients. The mean relative reduction of systolic and diastolic BP was 16 and 15% respectively and the mean time to the mean arterial pressure nadir was 59 minutes. Systolic BP fell by more than 30% in 4.6% of patients and diastolic BP and mean arterial pressure dropped by more than 30% in 4.2 and 3.3% of patients respectively. Patients over 60 years of age showed a significantly larger fall in systolic and diastolic BP. Patients with renal artery stenosis reached the BP nadir in a significantly shorter time compared with patients with essential hypertension (50.5 vs. 59.7 minutes, P less than 0.05) and showed a significantly larger fall in systolic BP (20.7 vs. 15.4%, P less than 0.05). A forward stepwise regression analysis showed that only baseline plasma renin activity had a significant relation to the fall in BP (P less than 0.01, R = 0.57). We conclude that according to our definition of a greater than 30% decrease of the mean arterial pressure, a first dose hypotension after captopril was seen in 3.3% of 240 patients. Captopril treatment should be introduced carefully since not all those patients at risk of hypotension can be identified in advance. PMID- 1629891 TI - The short term effects of oral labetalol in patients with chronic renal disease and hypertension. AB - This double-blind, controlled, crossover study compared the effects on blood pressure control, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) of labetalol, methyldopa and placebo in patients with chronic renal disease and hypertension. When compared with placebo, BP was significantly lower during treatment with both labetalol and methyldopa (P greater than 0.05) but did not differ significantly between the two active treatment periods; post-exercise heart rates were also significantly lower on labetalol than placebo (P less than 0.05). After treatment with labetalol, ERPF was significantly greater than with the placebo (P less than 0.05) but did not differ significantly between the active treatments. GFR did not differ significantly between the three groups. No significant differences were observed in haematology or liver function test results on labetalol compared with placebo. Labetalol is a safe and effective antihypertensive in patients with hypertension associated with chronic renal disease. In the short term it leads to an increase in ERPF which may be beneficial for such patients. PMID- 1629892 TI - Hypertension, obesity and response to antihypertensive treatment: results of a community survey. AB - A random sample of 2,854 subjects aged 35-64 was examined in the town of Vicenza (Italy) as part of the 'Hypertension Management Audit Project'. Pearson's correlation coefficient and multivariate analysis considering systolic and diastolic blood pressure, age and body mass index (BMI) were performed. SBP was more closely correlated with age than DBP. BMI correlated with both SBP and DBP, but very little with age. Fifty-seven percent of the men had a BMI of 25.5 or more and 49% of the women had a BMI of 24.5 or more. The quality of BP control in the treated patients was worse in the overweight when compared with the lean patients, although overweight and lean patients are treated with the same frequency. PMID- 1629893 TI - Headache in patients with uncontrolled BP on drug treatment. PMID- 1629894 TI - Epidemiological markers of Salmonella typhimurium isolates in Rome. AB - The phage type, antimicrobial resistance pattern, colicinogenic activity and DNA plasmid content of 172 strains of Salmonella typhimurium isolated in Rome from 1984 to 1986 were determined; 142 isolates were from patients with enteritis, 30 were from asymptomatic subjects. Most of the phage types identified were isolated during 2 or 3 of the study years; others, e.g., PT141, PT 204c and PT 194 were isolated during 1 year only, and only the last of these was isolated in large numbers. Phage typing proved most valuable in identifying epidemiologically related strains; DNA plasmid analysis was most useful in characterising further cultures of the same phage type, especially those isolated during suspected epidemics. PMID- 1629895 TI - Evaluation of methods for typing coagulase-negative staphylococci. AB - One hundred and forty-two coagulase-negative staphylococci (CNS) isolated from dialysate effluent or skin of patients receiving continuous ambulatory peritoneal dialysis (CAPD) were typed by extended antibiogram (16 antibiotics) and biotype (26 reactions). These isolates were then typed by supplementary methods to determine the most suitable typing method for an epidemiological study of antibiotic resistance. These included phage typing, reverse phage typing, plasmid typing, whole-cell protein typing by SDS-PAGE with analysis by densitometry, and immunoblotting. The percentage of isolates typed successfully by the supplementary methods were: phage typing 20%, reverse phage typing 0%, plasmid typing 66%, SDS-PAGE 100%, immunoblotting 100%. The discrimination of each method was: phage typing 20%, plasmid typing 37%, SDS-PAGE 69%, immunoblotting 57%. Reproducibility was 88% for phage typing and 97% for plasmid typing. The reproducibility of the whole-cell protein typing was 83% if the same extracts were used but only 43% when separate protein extracts were analysed on separate occasions. However, strain relatedness was highly reproducible. The determination of an antibiogram-biotype profile was not a sufficiently accurate typing method for an epidemiological study of antibiotic resistance. Whole-cell protein typing by SDS-PAGE or immunoblotting was technically demanding but was the most effective of the supplementary methods for detecting erroneous discrimination and false matching produced by antibiogram-biotype combinations. PMID- 1629896 TI - Cytopathic effects of Helicobacter pylori on cultured mammalian cells. AB - Cytopathic effects of broth-culture filtrates from eight clinical isolates and one reference strain of Helicobacter pylori on three cultured mammalian cell lines were investigated. All the strains, including NCTC 11637, produced cytotoxic factors that caused intracellular vacuolation on these cell lines. AGS and SflEp cells were more sensitive than HEp-2 cells. To examine the role of urease in the cytotoxic effect, a urease-negative mutant was produced. Filtrates from both wild-type and mutant strains produced similar vacuolation on SflEp cells in the absence of urea, suggesting that H. pylori produces a cytotoxic substance other than urease. In contrast, ammonia alone, or jack bean urease with urea, also induced rounding and detachment of SflEp cells, whereas ammonium salts induced the production of small vacuoles. The combination of the broth filtrate of the wild-type strain and urea induced vacuolation followed by rounding and detachment of SflEp cells. Evidence is presented that the latter changes are due to ammonia produced during incubation. Nevertheless, the amounts produced were less than that needed to induce cytopathic effects by itself. These results suggest that the cytotoxic substance induces intracellular vacuolation, and that the vacuolated cells are more susceptible to killing by ammonia. Thus both the cytotoxic substance and urease may contribute to the lethal cytotoxicity of H. pylori in vitro. PMID- 1629897 TI - Motility as a factor in the colonisation of gnotobiotic piglets by Helicobacter pylori. AB - Non-motile variants of Helicobacter pylori (strain 26695) occurred with a frequency of 1.6 (SD 0.4) x 10(-4) variants/cell/division cycle, and reversion to the motile form occurred with a frequency of less than 10(-7) variants/cell/division cycle. The two forms remained greater than 90% pure for up to 50 cell divisions and differed only in the presence or absence of motility and flagella. Bacteria were recovered from nine of 10 gnotobiotic piglets inoculated orally with motile H. pylori, but from only two of eight inoculated with the non motile variant. The motile form survived for 21 days in infected piglets, but the non-motile variant survived for only 6 days. Bacteria recovered from piglets inoculated with the non-motile variant were non-motile. These data support the hypothesis that motility is a colonisation factor for H. pylori. PMID- 1629898 TI - Cleavage of immunoglobulin A1, A2 and G by proteases from clinical isolates of Pasteurella multocida. AB - Several Pasteurella multocida strains were examined for their ability to produce extracellular enzymes that cleave immunoglobulin A and G (Ig A and Ig G) molecules. Two strains isolated from human pulmonary and genital infections produced proteases that cleaved human IgA and IgG, colostral IgA and human myeloma IgA1 and IgA2. Human IgM was not degraded by these enzymes. Examination of cleavage digests showed two main fragments with different electrophoretic mobilities. The two P. multocida strains produced a protease that cleaved IgA and IgG heavy chains outside the hinge region, and differed in this respect from the hinge-cutting proteases of other bacteria. Protease production may be a virulence mechanism for P. multocida strains. PMID- 1629899 TI - Effect of haemin limitation on the cytochrome complement and glucose metabolism of non-typable Haemophilus influenzae. AB - Haemophilus influenzae grown to exponential phase or stationary phase in medium with a low initial concentration of haemin (0.25 microgram/ml) was virtually devoid of cytochromes. Compared with bacteria grown in the presence of excess haemin (10 micrograms/ml), the haemin-limited organisms failed to respire formate and succinate and, generally, the respiratory rates with other substrates were reduced. However, growth rates were not affected by the haemin supply. Haemin limited growth was associated with a reduced efficiency of glucose utilisation, in terms of glucose growth yields, and affected the net levels of excreted organic acids. Haemin limitation resulted in reduced acetate and increased succinate accumulation in the culture medium and the novel presence of D-lactate. These results indicate that, in contrast to the phenotype expressed in vitro during conventional cultivation of H. influenzae, the haemin-limited phenotype, which may be expressed in vivo, is characterised by a lack of cytochromes and a shift towards a more anaerobic type of metabolism. PMID- 1629900 TI - Plasmid content and localisation of the STaI (STaP) gene in enterotoxigenic Escherichia coli with a non-radioactive polynucleotide gene probe. AB - Enterotoxigenic Escherichia coli (ETEC) strain P2200 of porcine origin possessed eight possibly plasmid-determined characters (K88+ Raf+ Hly+ Col+ Smr Tcr Su(r) STa+) and six plasmid DNA bands of 4.2-93 kb. Analysis of the spontaneous loss of characters and the results of matings with other E. coli strains revealed that the K88, Raf, Hly, Smr, Tcr and Su(r) characters could be transferred, and that the presence of the K88 and Raf characters was associated with an 83-kb plasmid. The presence and location of the STaI gene was investigated in several ETEC strains of bovine or porcine origin. Hybridisation with a non-radioactive polynucleotide probe associated the STaI gene with a plasmid in each strain; these plasmids were of 32-142 kb. In contrast, plasmids from a P2200 STa- variant and plasmids from two STa- variants of the bovine ETEC strain B41* (strain B41 obtained from a different source) did not hybridise with the probe. One of the B41*STa- variants had lost the STa plasmid, whereas the second variant retained a plasmid of the same size which did not hybridise. In contrast, a third B41*STa- variant retained a plasmid of the same size that still hybridised with the STaI probe. Plasmid DNA restriction fragment analysis, followed by hybridisation with the STaI probe, showed that the STaI gene was associated with 8.3-, 6.8- and 3.5 kb plasmid fragments in strain B41, and with 4.9-, 6.8- and 3.5-kb plasmid fragments in strain B41*, following digestion with EcoRI, BamHI, or EcoRI + BamHI, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629901 TI - Microbes in the air--when to count! (the role of air sampling in hospitals) PMID- 1629902 TI - Characterisation of non-pigmented species of the genus Prevotella by polyacrylamide gel electrophoresis. AB - Gram-negative anaerobic bacilli previously known as the melaninogenicus-oralis group of Bacteroides have been assigned to a new genus, Prevotella. The non pigmented members of this genus share several general characteristics and cannot be readily distinguished by routine tests. A polyacrylamide slab gel electrophoresis procedure, with visual analysis of protein patterns, was used to compare cellular protein patterns from clinical isolates with those from collection (reference) strains. Reference strains of P. oralis, P. veroralis, P. buccalis, P. oris, P. buccae, P. zoogleoformans, P. bivia, P. disiens, P. oulora, B. (P.) capillus and B. (P.) pentosaceus, and 91 non-pigmented isolates from patients with adult periodontal disease were examined by conventional biochemical tests, gas-liquid chromatography (GLC) and enzyme tests, and whole-cell protein profiles were obtained by SDS-PAGE. There was close correlation between patterns of results in biochemical and GLC tests and the SDS-PAGE profiles, and the species were readily distinguished in SDS-PAGE. The periodontal isolates were assigned to 10 groups by conventional test reaction patterns and nine groups by SDS-PAGE; the profiles of 79 isolates corresponded to those of seven species reference strains. By SDS-PAGE, clinical isolates of P. buccae (42 isolates) and P. oralis (eight isolates) showed good similarity with reference strains. However, for P. veroralis (15), P. oris (7), P. bivia (4), P. zoogleoformans (2) and P. buccalis (1), clinical isolates showed some minor variations from reference strains. Twelve isolates remained undesignated in SDS-PAGE analysis. Variant SDS-PAGE profiles divided clinical isolates of P. buccae into two subgroups and those of P. veroralis into five subgroups. PMID- 1629903 TI - High prevalence of stably derepressed class-I beta-lactamase expression in multiresistant clinical isolates of Enterobacter cloacae from Greek hospitals. AB - Susceptibilities to cefotaxime (Ctx) and ceftazidime (Caz) were examined for 90 recent clinical isolates of Enterobacter cloacae from Greek hospitals. Most (68%) of the isolates were resistant to both drugs, and all were resistant to cefoxitin. beta-Lactamase activities against cephaloridine in crude extracts from Ctx-Caz-resistant isolates were high, irrespective of whether or not the cells were grown with cefoxitin as an inducer of the chromosomal beta-lactamase, indicating stable derepression of the gene for the enzyme. On the other hand, double disk antagonism tests showed that all the Ctx-Caz-sensitive isolates possessed inducible expression of this beta-lactamase. Iso-electric focusing revealed the presence of five forms of the chromosomal beta-lactamase, randomly distributed amongst the Ctx-Caz-resistant and -sensitive isolates. Plasmid mediated beta-lactamases of TEM and PSE types also were found in many isolates. These data indicate that the extremely high prevalence of Ctx-Caz-resistant E. cloacae isolates in Greek hospitals is attributed to the dissemination of mutants which constitutively overproduce the class-I chromosomal beta-lactamase. Over 90% of these isolates exhibited cross-resistance to aminoglycosides, suggesting the accumulation of unrelated antibiotic resistance mechanisms. PMID- 1629904 TI - Analysis of genetic variability of penicillinase non-producing Neisseria gonorrhoeae strains with different levels of resistance to penicillin. AB - Genetic variability among 41 penicillinase non-producing Neisseria gonorrhoeae strains, isolated in Spain, with different levels of resistance to penicillin was investigated by multilocus enzyme electrophoresis. Based on the results obtained by analysis at seven enzyme loci, the strains were separated into 17 electrophoretic types. The average number of alleles/enzyme locus was 2.85; the mean genetic diversity/locus was 0.49 for individual isolates and 0.516 for electrophoretic types. The results showed that these gonococcal strains were, genetically, a highly variable group of organisms. PMID- 1629905 TI - Activation of skeletal muscle nicotinic acetylcholine receptors. AB - Work over the past ten years has greatly increased our understanding of both the structure and function of the muscle nicotinic acetylcholine receptor. There is a strongly supported general picture of how the receptor functions: agonist binds rapidly to sites of low affinity and channel opening occurs at a rate comparable to the agonist dissociation rate. Channel closing is slow, so the channel has a high probability of being open if both agonist-binding sites are occupied by ACh. Results of expression studies have shown that each subunit can influence AChR activation and have given a structural basis for the major physiological change known for muscle AChR, the developmental change in AChR activation. These general statements notwithstanding, there are still major areas of uncertainty which limit our understanding. We have emphasized these areas of uncertainty in this review, to indicate what needs to be done. First, the quantitative estimates of rate constants are not as strongly supported as they should be. The major reasons are twofold--uncertainties about the interpretation of components in the kinetic data and difficulties of resolving brief events. As a result, any inferences about the functional consequences of structural alterations must remain tenuous. Second, the functional behavior of individual AChRs is not as well understood as it should be. The kinetic behavior of an individual receptor clearly can be complex (section II). In addition, there is evidence that superimposed on this complexity there may be stable and kinetically distinguishable populations of receptors (section III). Until the basis for the kinetically defined populations is clarified, kinetic parameters for receptors of defined structure cannot be unambiguously obtained. Finally, it is not surprising that the studies of AChR of altered structure have not given definitive results. Two reasons should be apparent from the preceding points: there is not a fully supported approach for kinetic analysis, and the "normal" population may not be clearly defined. An additional complication is also emerging, in that the available data support the idea that specific residues distributed over all subunits may influence AChR activation. This possibility renders the task of analysis that much more difficult. The muscle nicotinic AChR has served as a prototype for the family of transmitter-gated membrane channels, which includes the muscle and neuronal nicotinic receptors, the GABAA, the glycine and possibly the non-NMDA excitatory amino acid receptor (Stroud et al., 1990). It is interesting to note that the functional properties of the GABAA receptor, probably the best-studied of the other members of the family are rather similar.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1629906 TI - K-induced alkalinization in all cell types of rabbit gastric glands: a novel K/H exchange mechanism. AB - Digital image processing of the pH-sensitive dye BCECF was used to examine the effects of high [K] media on cytoplasmic pH (pHi) of individual cells within isolated rabbit gastric glands. When cells were acidified to pHi 6.5 from the resting pHi of 7.2-7.3 and then exposed to solution containing 77 mM K plus amiloride (to block Na/H exchange), recovery to pHi 7.0 was observed. This K induced alkalinization occurred in all cell types of the gland, including cells within antral glands that were devoid of parietal cells (PC). This process was independent of extracellular Na and Cl and was unaffected by: 5 mM Ba or 200 microM bumetanide, or acute treatment with either 500 microM ouabain or 100 microM cimetidine, histamine or carbachol. SCH28080, which inhibits the PC H/K ATPase when used in the low microM range of concentrations, blocked the K effect on pHi at 100 microM but was ineffective at 1 microM. A similar pHi recovery was also stimulated by Li, Cs (both 72 mM), and Tl (10 mM), in the order Li greater than K greater than Cs greater than Tl (all in the presence of amiloride), and these alkalinizations were also blocked by 100 microM SCH28080. Parallel experiments were performed to test the effect of these ions on 14[C]-aminopyrine accumulation, an index of acid secretion by the H/K-ATPase at the lumenal membrane of the PC. There was no correlation between the rates of cation-induced pHi recovery from an acid load and H secretion as measured by the accumulation of aminopyrine. We conclude that the K- (and Cs- and Li-) dependent pHi recovery is mediated by a novel cation/H exchange mechanism that is distinct from the PC H/K ATPase. PMID- 1629907 TI - Regulatory volume increase in Ehrlich ascites tumor cells is mediated by the 1Na:1K:2Cl cotransport system. AB - After swelling in hyposmotic solution, Ehrlich ascites tumor cells shrink towards their original volume. Upon restoration of isosmolality (300 mOsM) the cells initially shrink but subsequently recover volume. This regulatory volume increase (RVI) is completely blocked when [Na+]o or [Cl-]o is reduced by 50% in the presence of normal [K+]o. With normal [NaCl]o but less than 2 mM [K+]o, not only is volume recovery blocked but the cells lose KCl and shrink. When [K+]o is increased to 5 mM there is a rapid net uptake of K+ and Cl- which results in volume recovery. This suggests that the reswelling phase requires the simultaneous presence of Na+, K+, and Cl-. Although ouabain has no effect on volume recovery, bumetanide completely blocks RVI by inhibiting a cotransport pathway that mediates the net uptake of Na+, K+ and Cl- in the ratio of 1Na:1K:2Cl. Na+ that accumulates is then replaced by K+ via the Na/K pump. PMID- 1629908 TI - Metastatic models and molecular genetics of prostate cancer. PMID- 1629910 TI - Treatment costs warrant closer look in clinical trials. PMID- 1629911 TI - Will NIH patent bid cause "land rush"? PMID- 1629909 TI - Racial variation in cancer incidence: fact or artifact? PMID- 1629912 TI - Doctors change breast cancer treatment practices. PMID- 1629913 TI - Scientists, activists discuss DES issues. PMID- 1629914 TI - Pilot study of interleukin-2 and lymphokine-activated killer cells combined with immunomodulatory doses of chemotherapy and sequenced with interferon alfa-2a in patients with metastatic melanoma and renal cell carcinoma. AB - BACKGROUND: Experiments in animal tumor models suggest that the antitumor effects of interleukin-2 (IL-2) or IL-2 in combination with lymphokine-activated killer (LAK) cells can be enhanced by chemotherapy agents such as cyclophosphamide or doxorubicin or by the biologic agent interferon alpha. PURPOSE: We determined the toxicity and clinical response rate of an IL-2-LAK cell regimen modified by the addition of moderate, immunomodulatory doses of chemotherapy and sequenced with interferon alfa-2a (IFN alpha-2a) in patients with metastatic melanoma and renal cell carcinoma. METHODS: IL-2 (3-6 million units/m2 per day) was administered by continuous infusion on days 0-5 and days 11-16. LAK cells were infused on days 11 and 12 or on days 11, 12, and 14. Low doses of cyclophosphamide (300 mg/m2) and doxorubicin (25 mg/m2) were given on day 9 before the LAK cell infusions. Following the IL-2-LAK cell infusion, IFN alpha-2a (12 million units/m2) was administered for a total of nine doses to complete a cycle of treatment. A total of 89 patients were enrolled in the study. RESULTS: For each histology, there were eight partial responses in 40 assessable patients, for an overall response rate of 20% (90% confidence interval = 10%-33%). The median response duration was 5 months, although two patients with renal cell carcinoma and one patient with metastatic melanoma had almost complete disappearance of tumor and are still responding after 26+, 22+, and 26+ months, respectively. Toxic effects were severe in patients receiving the highest dose of IL-2 administered in this study and similar to those reported with other high-dose IL-2-LAK cell regimens. Although toxic effects were completely reversible in most patients, there were four treatment-related deaths. CONCLUSIONS: This regimen is active in patients with metastatic melanoma and renal cell carcinoma and produces meaningful responses in a small percentage of these patients; however, it is not clear whether cyclophosphamide, doxorubicin, and IFN alpha-2a as used in this protocol appreciably augmented the antitumor activity of the IL-2-LAK cell regimen. PMID- 1629915 TI - Differences between black and white women with breast cancer in time from symptom recognition to medical consultation. Black/White Cancer Survival Study Group. AB - BACKGROUND: Studies in the United States have reported that Black women have higher fatality rates than White women following a diagnosis of breast cancer and are more likely to be diagnosed with late-stage cancers. PURPOSE: To evaluate reasons for these racial differences, we explored the difference between Black and White women in the length of time from symptom recognition to initial medical consultation. We also evaluated the extent to which other factors related to the length of this interval might contribute to any observed racial difference. METHODS: As part of a collaborative study of differences in the survival rates of Black patients and White patients with cancer, we interviewed a sample of 410 Black women and 325 White women from Atlanta, New Orleans, and San Francisco/Oakland who were newly diagnosed in 1985 or 1986 with invasive breast cancer. Retrospective data were collected on symptoms, dates of symptom recognition and initial medical consultation, and several other factors which may affect the interval between symptom recognition and medical consultation. Data were analyzed as if from a follow-up study, using product limit procedures and proportional hazards regression. RESULTS: At diagnosis, Black women with breast cancer were two times more likely to have stage IV breast cancer and one and one half times more likely to have stage III breast cancer than White women with breast cancer and were only approximately one-half as likely to have stage I breast cancer. Similarly, Black women were almost twice as likely as White women to have tumors that were larger than 5 cm or tumors that had extensions to the chest wall or skin at presentation. However, the average rate at which Black women with breast cancer obtained an initial medical consultation lagged behind that for White women by only a slight but statistically significant difference (15%). The median time between symptom recognition and medical consultation was slightly longer for Black women (16 days) than for White women (14 days) (P = .06). Adjustment for other characteristics predictive of the length of this interval had little effect on racial differences. The racial differences tended to vary somewhat by age and metropolitan area, suggesting that the results may not apply equally to all demographic subgroups and regions in the United States. CONCLUSION: This small difference in the time from symptom recognition to medical consultation is unlikely to account for the large racial differences in survival rates and in stage of disease at the time of diagnosis. PMID- 1629916 TI - Racial misclassification of Native Americans in a surveillance, epidemiology, and end results cancer registry. AB - BACKGROUND: The cancer incidence for all sites has been reported to be lower in Native Americans than in White Americans. Concerns have been expressed, however, that the observed low incidence may be a result of inaccurate reporting of race. PURPOSE: The objective of this study was to investigate the extent to which racial misclassification may contribute to the observed low cancer incidence among Native Americans. METHODS: A registry of individuals eligible to receive medical services funded by the Indian Health Service was linked by computer to the Puget Sound Surveillance, Epidemiology, and End Results (SEER) cancer registry. RESULTS: Only 137 (60%) of the patients with invasive cancer registered with the Indian Health Service and for whom race was recorded were identified as Native Americans in the SEER registry. Similarly, 55 (69%) of 80 in situ cervical cancer case patients were classified as Native American. A strong association was observed between Native-American blood quantum level and racial misclassification. CONCLUSION: The results of this study indicate that the observed low cancer incidence in Native Americans relative to Whites in the northwest United States is at least partially attributable to racial misclassification in the SEER cancer registry. PMID- 1629918 TI - Patient education in the rural community health center. PMID- 1629917 TI - Relationship of polyps to cancer of the large intestine. AB - BACKGROUND: Pathologic and epidemiologic evidence indicates that patients with sporadic (nonfamilial) adenomatous polyps of the large intestine are at high risk of developing colorectal cancer. PURPOSE: Our primary goal in this study was to evaluate the colorectal cancer mortality rate among persons who have had a histologically confirmed benign colorectal polyp. METHODS: We used the retrospective follow-up method to evaluate the risk of death from colorectal cancer in 2872 Rhode Island men and women who were 24 through 79 years of age at the time of surgery for benign polyps in the years 1959 through 1975. RESULTS: Among 2872 subjects, the mortality from colorectal cancer, standardized for age, sex, and calendar time, was estimated as 1.74 (95% confidence interval = 1.44 2.09) times the rate in the general population of Rhode Island residents. Colorectal cancer mortality was higher in the first 5 years of follow-up than it was later. There was little relationship between the numbers of polyps and colorectal cancer mortality, and there was only a modest association between the size of polyps and mortality. Colorectal cancer mortality was more than twice as high in subjects whose polyps were proximal to the sigmoid compared with those with sigmoid or rectal polyps. The observed elevation of risk of colorectal cancer was almost entirely confined to subjects who had an adenomatous polyp. The risk increased strongly with the percentage of villous features in the polyp and was about twice as high in subjects with villous adenoma than in those with other adenomatous polyps. CONCLUSIONS: Our results support the suspected relationship between colorectal polyps and cancer incidence and extend the association to colorectal cancer mortality. PMID- 1629919 TI - Health promotion at its best. PMID- 1629920 TI - Quality of care and black American patients. AB - Even with major advancements in medical knowledge and significant improvements in health sciences technology, evidence still exists that blacks do not enjoy as full a measure of health as do other racial and ethnic groups. To attempt a better understanding of this situation, literature was reviewed to consider relationships between being black and issues related to quality of health care. It was determined that these relationships have not been studied to any great extent, either in quantity or quality. When such studies have been undertaken, they have been limited to mostly qualitative designs, and appropriate controls for confounding variables have been minimal. The psychiatric literature reports most of the studies with very few studies found in the literature of other specialties. A conceptual model is presented regarding race-related research. It is argued that a first step might be to study whether the quality of care differs when the physician and the patient are members of different racial groups compared with when the physician and patient are members of the same racial group. In all race-related research, it is necessary to carefully consider specific variables that may confound results, eg, diagnostic errors, age, sex, socioeconomic status, level of education, geographic locale, and method of payment for health-care services. PMID- 1629921 TI - Phototoxicity and the cornea. AB - The cornea is sensitive to the effects of ultraviolet (UV) light and can suffer both acute and chronic toxicity. Ultraviolet keratitis is associated with relatively short exposures to light sources such as welding arcs or tanning lamps. The corneal effects are seen within a few hours following exposure and typically will resolve within 72 hours. Chronic exposure to environmental UV light may lead to a variety of ocular surface abnormalities that rarely resolve in the absence of therapy. Ultraviolet light, while potentially destructive, also can be used therapeutically. Recently, the photoablative properties of the excimer laser have been used in corneal refractive surgery. This laser uses UV light to break chemical bonds and remove tissue. Corneal phototoxicity is a reflection of the sensitivity of the ocular surface to photochemical injury. Fortunately, effective protection in the form of UV-blocking lenses is widely available. PMID- 1629922 TI - A culturally sensitive approach to the prevention of interpersonal violence among urban black youth. AB - Black-on-black interpersonal violence is a major problem for black youth living in poor urban areas. Diverse lines of research converge to suggest that interpersonal violence among inner-city black youth may result from a combination of environmental stressors, racial identity problems, and health and mental health problems. A culturally sensitive approach to the prevention of interpersonal violence among black youth is described. It is concluded that insensitivity to the significant role of racial or cultural factors in black-on black violence contributes to the relative inattention to the problem. PMID- 1629923 TI - Body temperature and its relationship to demographic and cardiovascular risk factors in a national sample of children and adolescents. AB - The association of body temperature with demographic, maturational, constitutional, and cardiovascular risk variables was investigated in a large, representative sample of US children and adolescents in the Health Examination Survey. While body temperatures in children ages 6 to 11 years were not related to demographic variables, temperatures in children ages 12 to 17 were lower at older ages, higher in females than males, and higher in whites than blacks. In multiple regression analyses, demographic variables, maturational variables, and variables related to heat production or loss explained less than 10% of the variation in body temperature. Body temperature was a significant independent correlate of resting heart rate and systolic blood pressure at ages 6 to 11 and 12 to 17. Body temperature showed weak tracking over a follow-up interval averaging 44 months. PMID- 1629924 TI - J type diabetes revisited. AB - J type diabetes is grouped as a subtype of type III or malnutrition-related diabetes, known as protein-deficient pancreatic diabetes, (PDPD). J type diabetes has not been reported recently, but a clinical picture called phasic insulin dependent diabetes mellitus (PIDDM) has been elaborated in Jamaica, the same home country of PDRD and appears to be a "formes frustes" syndrome. The following comparative studies were performed on a group of diabetic patients and normal controls: insulin receptor binding; renal, hepatic, and pancreatic function; and abdominal ultrasonography. The results show a considerably decreased white and red blood cell binding to insulin (P less than .05), extensive kidney damage (P less than .05), and increased pancreatic echogenicity in PIDDM, supporting a separate identity of this latter syndrome from types I and II diabetes mellitus. Also, the features of relative insulin resistance, absence of ketosis even in the presence of severe hyperglycemia, and intermittent insulin requirement suggests that PIDDM, J type diabetes, and PDPD are one and the same syndrome. PMID- 1629925 TI - Elevated immunoreactive tumor necrosis factor and interleukin-1 in sickle cell disease. AB - To determine whether tumor necrosis factor (TNF) and interleukin-1 (IL-1) might be involved in the pathogenesis of sickle cell disease and its complications, TNF alpha and IL-1-alpha were measured using enzyme-linked immunosorbent assay in 59 plasma samples from 34 adult subjects with Hb SS or Hb SC who did not have documented infections. Tumor necrosis factor was elevated on at least one occasion in 27 subjects, including 18 of 21 subjects in the steady state and 13 of 19 subjects during painful crisis. Interleukin-1 was elevated on at least one occasion in 6 subjects, including 3 subjects in the steady state and 3 subjects in crisis. All subjects with elevated IL-1 also had elevated TNF. Tumor necrosis factor and IL-1 were similarly elevated in the steady state and during painful crisis. No correlation was noted between TNF or IL-1 levels and the extent of activation of coagulation, as measured by plasma levels of the fibrin D-dimer fragment, the overall severity of vascular occlusive disease in each subject, or the presence of specific vascular occlusive complications. We conclude that plasma TNF is frequently elevated in subjects with sickle cell disease, and IL-1 is also elevated in some subjects. A direct role for these cytokines in the pathogenesis of vascular occlusion in sickle cell disease was not demonstrated, but an indirect role was not excluded. PMID- 1629926 TI - Rhabdomyolysis: report of eleven cases. AB - This article reports the results of a retrospective study of 11 patients with rhabdomyolysis-induced acute renal failure. All patients had multiple risk factors for rhabdomyolysis, the most common of which were alcoholism, illicit drug abuse, compression, and trauma. Patients with combined alcohol/illicit drug abuse had more severe electrolyte imbalances than patients without alcohol/illicit drug abuse. Myoglobinuria was detected in only half the patients despite rhabdomyolysis and urine "hematest" positivity. The serum creatine phosphokinase level was elevated in all of the patients, which is a good marker for rhabdomyolysis. Rhabdomyolysis is a relatively common disorder in municipal hospitals. Routine serum creatine phosphokinase levels should be checked on patients at risk, especially alcoholics, illicit drug abusers, and older patients. PMID- 1629927 TI - Disorders of serum calcium in acquired immunodeficiency syndrome. AB - This study assessed the incidence of abnormal serum calcium levels in patients with acquired immunodeficiency syndrome (AIDS). A retrospective review of 66 patients with AIDS in an inner-city hospital was done. Fifty-four patients were intravenous drug abusers, and two patients were male homosexuals. None of the patients had lymphoma. Of the 66 patients, 17.9% were found to have hypocalcemia and 2.9% had hypercalcemia. The possible causative mechanisms are discussed. PMID- 1629928 TI - Multicentric gastrointestinal and extraintestinal leiomyosarcomatosis: a case report. AB - This article presents a case of synchronous polypoid primary adenocarcinoma of the transverse colon without lymph node or distance metastasis. During the postmortem examination, polypoid smooth muscle tumors in the patient's gastrointestinal tract and extensive extraintestinal smooth muscle tumors in the patient's liver, lungs, and visceral organs, including the diaphragm, parathyroid gland, bone marrow of the vertebrae, and subcutaneous tissue of the left wrist, were reviewed to determine their origin. Histomorphologically, all of the tumors were classified as leiomyosarcomas. PMID- 1629929 TI - Neonatal pneumoperitoneum of uncertain etiology. AB - This article describes a case of pneumoperitoneum in a newborn who had no evidence of an associated pulmonary air leak. PMID- 1629930 TI - The oath of Imhotep: in recognition of African contributions to Western medicine. PMID- 1629931 TI - Cancer in the African American. The annual William E. Allen, Jr, MD, Memorial Lecture. PMID- 1629932 TI - Mutagenicity of trinitrotoluene and its metabolites formed during composting. AB - TNT was mutagenic for Salmonella typhimurium without the need of a rat liver metabolic activation system (S9). The mutagenic potency of TNT decreased in proportion to the number of nitro groups that were reduced to the amino form. The presence of a nitro group on the 4 position of the diamino congener is necessary for mutagenicity. Among the active congeners, mutagenicity was generally greater for TA100 than TA98, except that for the 4-amino congener the reverse was true. In cases when S9 was included in the assay, there was always a decrease in the number of mutants induced as compared with those without S9. Tetryl behaved like TNT, except that it was approximately three times more potent. RDX and HMX were not mutagenic under the conditions of the assay. When TNT was composed, the major metabolites identified in organic extracts of compost samples were the 2-amino and 4-amino congeners. An acetonitrile extract of compost was tested and found to be more mutagenic for TA98 than TA100, much like the authentic 4-amino congener, but the amount of this congener in the extract did not account for the degree of mutagenicity. PMID- 1629933 TI - Reevaluation of benzene exposure for the Pliofilm (rubberworker) cohort (1936 1976). AB - The Pliofilm cohort is the most intensely studied group of workers chronically exposed to benzene. Information on this cohort has been the basis for regulations and/or guidelines for occupational and environmental exposure to benzene. Rinsky et al. (1986, 1987) and Crump and Allen (1984) developed different approaches for reconstructing the exposure history of each member of the group. The predicted levels of exposure, combined with the data on the incidence of disease, have been used to estimate benzene's carcinogenic potency. In this paper, recent information from worker interviews and historical records from the National Archives and elsewhere were used to evaluate the accuracy of prior exposure estimates and to develop better ones for the cohort. The following factors were accounted for: (1) uptake of benzene due to short-term, high-level exposure to vapors, (2) uptake due to background concentrations in the manufacturing building, (3) uptake due to contact with the skin, (4) morbidity and mortality data on workers in the Pliofilm process, (5) the installation of industrial hygiene engineering controls, (6) extraordinarily long work weeks during the 1940s, (7) data indicating that airborne concentrations of benzene were underestimated due to inaccurate monitoring devices and the lack of adequate field calibration mated due to inaccurate monitoring devices and the lack of adequate field calibration of these devices, and (8) likely effectiveness of respirators and gloves. Our estimates suggest that Crump and Allen (1984) overestimated the exposure of workers in some job classifications and underestimated others, and that Rinsky et al. (1981, 1986) almost certainly underestimated the exposure of nearly all workers. Airborne concentrations of benzene at the St. Marys facility during the years of its operation were found (on average) to be about half those of the two Akron facilities. Our analysis indicates that short-term, high-level exposure to benzene vapors and dermal exposure significantly increased (by about 25-50%) the total absorbed dose of benzene for some workers. One of the key findings was that, unlike prior analyses, the three facilities probably had significantly different airborne concentrations of benzene, especially during the 1940s and 1950s. PMID- 1629934 TI - Percutaneous penetration of 2,4-dichlorophenoxyacetic acid and 2,4-D dimethylamine salt in human volunteers. AB - The percutaneous penetration of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4-D dimethylamine salt (DMA) was evaluated separately in five male volunteers who participated in both experiments. Urine samples collected for 144 h following dermal applications of 10 mg to the dorsum of the hand (9 cm2) were analyzed for 2,4-D. Following the acid application, an average of 4.46 +/- 0.849% was recovered in the urine and a significantly lower amount of 1.76 +/- 0.568% following the DMA application. Significantly higher amounts of 2,4-D DMA (7.68 +/ 0.493 mg) were washed off the hand 6 h following application as compared with 2,4-D acid (5.35 +/- 0.384 mg). These results indicate that, in addition to the differences in physical and chemical properties of the two compounds that will affect absorption, the amount of the chemical absorbed is related inversely to the amount of washed off. Urinary excretion of 2,4-D was not complete in all volunteers 144 h following either application, but in all cases it was approaching the limit of detection. An average of 84.8 +/- 2.55% and 76.8 +/- 8.05% of the total recovered in 144 h was recovered in the urine 96 h following 2,4-D acid and 2,4-D DMA application, respectively. Average, approximated half lives for excretion were 39.5 +/- 8.1 h for the acid application and 58.5 +/- 13.2 h for the DMA application. PMID- 1629935 TI - Dermal absorption of the phenoxy herbicide 2,4-D dimethylamine in humans: effect of DEET and anatomic site. AB - Percutaneous absorption of the 14C-ring-labeled phenoxy herbicide 2,4-D-amine (2,4-dichlorophenoxyacetic acid dimethylamine) was examined following topical applications of the herbicide to the palm and forearm of human volunteers. The effect of two vehicles (water and acetone) and the mosquito repellent DEET (N,N diethyl-m-toluamide) on dermal absorption of 2,4-D-amine also was investigated. The total percent dermal absorption was calculated from the mean percent urinary recoveries and was not corrected for nonurinary excretion. The data revealed 14 +/- 4.5% (standard deviation) and 10 +/- 11.5% palmar absorption of 2,4-D-amine applied in water, with and without DEET, respectively, and 7 +/- 6.2% and 13 +/- 5.0% forearm absorption of the herbicide applied in water or acetone, respectively. Soap-and-water skin washes conducted at 24 h posttreatment removed up to 34% of the applied dose. Successive tape strips of skin taken at 24 h posttreatment demonstrated generally decreasing herbicide levels in the outer layers. The data bring into question the complete validity of the rhesus monkey model to predict human dermal absorption. PMID- 1629936 TI - Dermal penetration of [14C]captan in young and adult rats. AB - Age dependence in dermal absorption has been a major concern in risk assessment. Captan, a chloroalkyl thio heterocyclic fungicide, was selected for study of age dependence as representative of this class of pesticides. Dermal penetration of [14C]captan applied at 0.286 mumol/cm2 was determined in young (33-d-old) and adult (82-d-old) female Fischer 344 rats in vivo and by two in vitro methods. Dermal penetration in vivo at 72 h was about 9% of the recovered dose in both young and adult rats. The percentage penetration was found to increase as dosage (0.1, 0.5, 2.7 mumol/cm2) decreased. Two in vitro methods gave variable dermal penetration values compared with in vivo results. A static system yielded twofold higher dermal penetration values compared with in vivo results for both young and adult rats. A flow system yielded higher dermal penetration values in young rats and lower penetration values in adults compared with in vivo results. Concentration in body, kidney, and liver was less in young than in adult rats given the same absorbed dosage. A physiological pharmacokinetic model was developed having a dual compartment for the treated skin and appeared to describe dermal absorption and disposition well. From this model, tissue/blood ratios of captan-derived radioactivity for organs were found to range from 0.35 to 3.4, indicating no large uptake or binding preferences by any organ. This preliminary pharmacokinetic model summarizes the experimental findings and could provide impetus for more complex and realistic models. PMID- 1629937 TI - Delayed health sequelae of accidental exposure to bromine gas. AB - The delayed health effects from accidental exposure to bromine vapors in a group of six people were evaluated. During the acute exposure, they had only some respiratory symptoms and skin burns of first to second degree involving small areas. All were treated in one hospital and released within 1-4 d. Six to 8 wk later, some still had health complaints such as cough, shortness of breath, chest tightness, eye irritation, headache, dizziness, fatigue, and memory, sleep, and sexual disturbances, but no objective laboratory or clinical evidence of effects. Mechanisms that might have led to manifestations of such complaints 1-2 mo after the accident are discussed and possible ways to alleviate similar situations are suggested. PMID- 1629938 TI - Isolation of cDNA clones encoding rat glial fibrillary acidic protein: expression in astrocytes and in Schwann cells. AB - Glial fibrillary acidic protein (GFAP) expressed by astrocytes in the central nervous system (CNS) has been extensively characterized but the molecular identity of related molecules in the peripheral nervous system (PNS) remains unclear. To examine possible structural differences between CNS and PNS GFAP, we have isolated cDNA clones for rat GFAP from both cultured astrocyte and Schwann cell libraries. Nucleotide sequence analysis indicated that the PNS and CNS GFAP clones contained identical coding regions, with a predicted protein product of 430 amino acids. However, the 5'-untranslated region of clone rGFA15, isolated from the Schwann cell library, was longer than that predicted for brain-derived GFAP mRNA. Primer extension analysis of RNA isolated from the RT4-D6 Schwann cell line indicated that the start site for PNS GFAP mRNA lies 169 bases upstream from that used in the CNS. In addition, tryptic peptide mapping of GFAP prepared from cultured astrocytes and Schwann cells revealed one major peptide fragment present in CNS GFAP but absent from PNS GFAP. These results suggest structural differences between GFAP in these two cell types, at both the nucleic acid and protein level, and are consistent with previous observations of immunochemical differences existing between CNS and PNS GFAP. PMID- 1629939 TI - Exogenous gangliosides modulate calcium fluxes in cultured neuronal cells. AB - Previous work from this and other laboratories has shown that the neuritogenic effect due to exogenous gangliosides on primary neurons in culture is accompanied by several morphological and biochemical modifications. The present results indicate that the treatment of these neurons with gangliosides, under the experimental conditions which are known to produce a sprouting effect, inhibited the influx of 45Ca2+ and increased the release of 45Ca2+ from the cells. No significant differences were noted using concentrations of gangliosides (10(-8) 10(-5) M) either below or above the critical micellar concentrations. No apparent specificity was observed among various species of individual sialocompounds (GM1, GD1a). Moreover the presence or absence of fetal calf serum in the culture medium influenced the levels of 45Ca2+ fluxes. This study confirms the hypothesis that gangliosides may be considered as Ca2+ flux modulators in neuronal cells. PMID- 1629940 TI - Establishment and characterization of a mouse Schwann cell line which produces myelin in vivo. AB - A Schwann cell line (MSC 80) was established from purified mouse Schwann cell cultures using large doses of serum. MSC 80 cell line is an aneuploid cell line which has a doubling time of 17 hr and has been maintained through more than 110 passages. Most of MSC 80 cells are of bipolar or stellate (3-5 processes) shape. A few others are irregular in shape, gigantic, and multinucleated. All MSC 80 cells express antigens of myelin-forming Schwann cells such as S-100, 224/58, laminin, and other glycoproteins of the extracellular matrix. However, they also express the non-myelin-forming Schwann cell antigen GFAP. By time-lapse cinematography, MSC 80 cells exhibit the Schwann cell characteristic rhythmical undulations. When induced to form aggregates in agar, they form intercellular junctions and basement membrane-like structures. In addition, after transplantation in or at a distance from a lysolecithin induced lesion, MSC 80 cells form myelin around the host demyelinated axons. MSC 80 cells thus express, when isolated in vitro, some of the normal myelin-forming Schwann cell phenotype. In addition, they present the major advantage of forming myelin when associated with axons in vivo. PMID- 1629941 TI - Cloning of cDNAs encoding human S-100 alpha and beta subunits and their differential expression in human tumor cell lines. AB - We isolated nearly full-length clones of S-100 alpha and beta subunit cDNAs from a human brain cDNA library. The alpha subunit cDNA was 579 bp long and contained 99 bp of 5'-noncoding region, 282 bp of coding region, and 198 bp of 3'-noncoding region. The beta subunit cDNA was 743 bp long and contained 57 bp of 5'-noncoding region, 276 bp of coding region, and 410 bp of 3'-noncoding region. An amino acid sequence comparison between human and bovine alpha subunits and between human and rat beta subunits showed that both subunits were nearly entirely conserved. The amino acid sequences of human alpha and beta subunits were conserved at both Ca(2+)-binding domains. Northern blot analysis of brain RNA showed that human alpha and beta subunit cDNA probes discriminated between alpha and beta subunit mRNAs. By using these subunit-specific cDNA probes, it was demonstrated that alpha and beta subunit mRNAs were expressed in different manners among tumor cell lines: beta was detected in melanoma and some glioma cell lines, while alpha was detected only in a melanoma cell line. Southern blot analysis showed that there were no major deletions and rearrangements of alpha and beta subunit genes in these cell lines, regardless of the level of alpha and beta subunit expression, suggesting that the expression of these subunits may be regulated at the transcriptional or RNA stability level. PMID- 1629942 TI - beta-Amyloid precursor protein of Alzheimer's disease in cultured bovine oligodendrocytes. AB - The production of beta-amyloid precursor protein (beta APP) in cultured oligodendrocytes isolated from adult bovine brains was examined by immunohistochemistry and immunoblotting. Immunostaining of oligodendrocytes with antibodies specific for the carboxy terminus of beta APP demonstrated positive immunoreactivity of oligodendroglial cytoplasm. Immunoblot analysis of cellular extracts detected two distinct bands with estimated molecular weight of 118 and 105 kDa. The amount of these beta APP subspecies increased considerably in response to their attachment to the poly-L-lysine substratum. PMID- 1629943 TI - Expression cloning of neurotrophic factors using Xenopus oocytes. AB - We have explored the potential for cloning novel neurotrophic factor cDNAs via assay of neurotrophic activities following expression in Xenopus oocytes. In this report, we describe the successful application of the method to tract rat ciliary neurotrophic factor (CNTF) activity from mRNA purified from cultured cells and from mRNA synthesized by in vitro transcription of a cDNA library. Rat C6 glioma cells, which had been previously shown to have CNTF-like activity (Westermann et al., 1988), were used as source material. We tested protein extracts of C6 cells using an in vitro assay of primary neurons from the chick ciliary ganglion (CCG assay) and detected a CNTF-like activity. RNA isolated from C6 cells was shown to direct the synthesis of the activity following microinjection into Xenopus oocytes and one-step fractionation of Xenopus extract. C6 mRNA was size fractionated, and fractions encoding CNTF-like activity were cloned into a lambda phage vector at a site distal to a T7 promoter. Synthetic RNA transcribed from total library DNA was injected into Xenopus oocytes, and a CNTF-like activity in the oocyte extract was detected by the CCG assay. Further fractionation of library clones narrowed the presence of the clone encoding the CNTF-like activity to a pool containing 20,000 members. The presence of a full-length CNTF cDNA clone in this pool and partial clones in other pools was confirmed by Polymerase Chain Reaction (PCR) using oligonucleotides from the rabbit CNTF cDNA (Lin et al., 1989) as primers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1629944 TI - Decorin, a chondroitin/dermatan sulfate proteoglycan is under neural control in rat skeletal muscle. AB - Proteoglycans (PGs) are abundant components of the extracellular matrices (ECM) of skeletal muscle. We have previously found that the synthesis of skeletal muscle PGs present at the ECM increase after denervation. The experiments reported here were undertaken to identify which PG(s) increase after denervation of rat leg muscles. Incorporation of radioactive sulfate demonstrated the presence of a chondroitin/dermatan sulfate PG of 70-90 kDa in the skeletal muscle ECM, which increased after denervation. The PG has a core protein of 39-45 kDa after treatment with chondroitinase ABC. Antibodies against rat decorin, a chondroitin/dermatan sulfate PG synthesized by various cell types, specifically immunoprecipitated this PG from a mixture of PGs. Immunocytolocalization of this PG indicated that the chondroitin/dermatan sulfate PG accumulates at the perimysium of skeletal muscle after denervation. Finally, Northern blot analysis indicated an increase of muscle transcripts for decorin after denervation. The data reported here suggest that a chondroitin/dermatan sulfate PG present at the skeletal muscle ECM, very similar if not identical to decorin, increases after denervation. PMID- 1629945 TI - Transcriptional regulation of glial fibrillary acidic protein (GFAP)-mRNA expression during postnatal development of mouse brain. AB - During mouse brain maturation, GFAP-mRNA undergoes a two-step developmental expression. It increases between birth and day 15 (period of astrocytic proliferation) and then decreases until day 55 (period of astrocytic morphological differentiation). We have developed an in vitro transcription procedure, as a mean to study the part of transcriptional control in this biphasic expression. After RNA synthesis by endogenous RNA polymerases in nuclei isolated from mouse brain (of 3 to 55 days and 217 days), the relative rates of GFAP-mRNA transcripts were analysed by hybridization with a specific cDNA probe. As early as 3 days after birth, the rate of GFAP-mRNA transcripts was maximal, whereas unexpectedly, it showed a significant decrease in mice of 15 days and stayed low until the 55th day. Therefore, a transcriptional control may take place early in mouse brain postnatal development by increasing the transcriptional rate of the GFAP gene in astrocytes, and during the transition from proliferation to differentiation phase of astrocytes (that occurs at the 15th day after birth) by decreasing this rate. However, posttranscriptional events may also occur to modulate the level of the cytoplasmic GFAP-mRNA. In older mice (217 days), the low rate of GFAP-mRNA transcripts found is not concordant with the high cytoplasmic level generally observed in gliosis of the aging brain. Our data suggest posttranscriptional events at this age. PMID- 1629946 TI - Changes in taurine transport evoked by hyperosmolarity in cultured astrocytes. AB - Cultured astrocytes grown chronically (1-3 days) in medium made hyperosmotic (450 mOsm) with NaCl or sucrose showed an increase in taurine concentration from 294 to 501 nmol/mg protein in NaCl and to 382 nmol/mg protein in sucrose. The effect of hyperosmolarity on taurine uptake and release was examined to investigate whether or not changes in these processes may account for the increase observed in cell taurine content. Hyperosmolarity significantly affected the two components of taurine uptake (i.e., the Na(+)-dependent and the diffusional component). The Vmax of the Na(+)-dependent, active transport increased 50%, whereas no change was observed in the Km. The diffusion coefficient was markedly decreased by hyperosmolarity, being 2.2 x 10(-4) and 6.6 x 10(-6) ml/min/mg protein in isosmotic and hyperosmotic conditions, respectively, indicating a blockade of the leak pathway. These changes in the active and passive components of taurine transport were opposite to those induced by hyperosmolarity. The effect of hyperosmolarity increasing cell taurine content was insensitive to cycloheximide and colchicine. The basal efflux of taurine from astrocytes also decreased in cells exposed to hyperosmotic medium, indicating that alterations in both influx and efflux of taurine are involved in the mechanism responsible for the increase in taurine levels induced by hyperosmolarity in astrocytes. PMID- 1629947 TI - One hundred years of virology. PMID- 1629948 TI - Mechanism of attenuation of a chimeric influenza A/B transfectant virus. AB - The ribonucleoprotein transfection system for influenza virus allowed us to construct an influenza A virus containing a chimeric neuraminidase (NA) gene in which the noncoding sequence is derived from the NS gene of influenza B virus (T. Muster, E. K. Subbarao, M. Enami, B. P. Murphy, and P. Palese, Proc. Natl. Acad. Sci. USA 88:5177-5181, 1991). This transfectant virus is attenuated in mice and grows to lower titers in tissue culture than wild-type virus. Since such a virus has characteristics desirable for a live attenuated vaccine strain, attempts were made to characterize this virus at the molecular level. Our analysis suggests that the attenuation of the virus is due to changes in the cis signal sequences, which resulted in a reduction of transcription and replication of the chimeric NA gene. The major finding concerns a sixfold reduction in NA-specific viral RNA in the virion, causing a reduction in the ratio of infectious particles to physical particles compared with the ratio in wild-type virus. Although the NA-specific mRNA level is also reduced in transfectant virus-infected cells, it does not appear to contribute to the attenuation characteristics of the virus. The levels of the other RNAs and their expression appear to be unchanged for the transfectant virus. It is suggested that downregulation of the synthesis of one viral RNA segment leads to the generation of defective viruses during each replication cycle. We believe that this represents a general principle for attenuation which may be applied to other segmented viruses containing either single-stranded or double-stranded RNA. PMID- 1629949 TI - Editing on the genomic RNA of human hepatitis delta virus. AB - It has been shown previously that during replication of the genome of human hepatitis delta virus (HDV), a specific nucleotide change occurs to eliminate the termination codon for the small delta antigen (G. Luo, M. Chao, S.-Y. Hsieh, C. Sureau, K. Nishikura, and J. Taylor, J. Virol. 64:1021-1027, 1990). This change creates an extension in the length of the open reading frame for the delta antigen from 195 to 214 amino acids. These two proteins, the small and large delta antigens, have important and distinct roles in the life cycle of HDV. To further investigate the mechanism of this specific nucleotide alteration, we developed a sensitive assay involving the polymerase chain reaction to monitor changes on HDV RNA sequences as they occurred in transfected cells. We found that the substrate for the sequence change was the viral genomic RNA rather than the antigenomic RNA. This sequence change occurred independently of genome replication or the presence of the delta antigen. Less than full-length genomic RNA could act as a substrate, but only if it also contained a corresponding RNA sequences from the other side of the rodlike structure, which is characteristic of HDV. We were also able to reproduce the HDV base change in vitro, by addition of purified viral RNA to nuclear extracts of cells from a variety of species. PMID- 1629950 TI - Interferon-induced human protein MxA is a GTPase which binds transiently to cellular proteins. AB - MxA is an abundant and ubiquitous cytoplasmic protein induced by alpha/beta interferon in human cells. Upon full induction, it can constitute 0.5 to 1% of cytosolic proteins. MxA can bind elements of the cytoskeleton, such as actin and tubulins, and several larger cellular proteins. However, these protein-protein interactions seem to be transitory. The human MxA protein contains a tripartite GTP-binding domain consisting of GxxxxGKS, DxxG, and TKxD, where x is any amino acid. It is shown here that the native MxA protein has GTPase activity (GTP--- GDP) when purified by immunoprecipitation with affinity-purified polyclonal antibodies directed against the C-terminal domain of MxA. The GTPase activity is greatly diminished by polyclonal antibodies directed against the N-terminal domain of MxA (the domain which contains the GTP-binding consensus elements). Amino acid substitution within the GTP-binding domain abolished the GTPase activity of the mutated MxA protein expressed in transfected CHO cells. The reaction is specific for GTP, and the approximate Km is 0.1 mM. The reaction has an absolute requirement for Mg2+. The turnover number is approximately 70 molecules of GTP hydrolyzed per min per MxA molecule. It is suggested that the human MxA protein has certain characteristics of the stress proteins. PMID- 1629951 TI - Mutational analysis of the core, spacer, and initiator regions of vaccinia virus intermediate-class promoters. AB - Activation of vaccinia virus late gene transcription is dependent on DNA replication and the expression of three genes: A1L, A2L, and G8R (J. G. Keck, C. J. Baldick, Jr., and B. Moss, Cell 61:801-809, 1990). To fully characterize the promoter elements of these trans-activator genes, we prepared more than 140 plasmid vectors containing natural and mutated DNA segments ligated to the Escherichia coli lacZ or chloramphenicol acetyltransferase reporter gene. Expression of the reporter genes occurred when the plasmids were transfected into vaccinia virus-infected cells and was enhanced when DNA replication was prevented, indicating that the A1L, A2L, and G8R promoters belong to the intermediate regulatory class. Deletional mutagenesis demonstrated that the regulatory elements of all three promoters extended between 20 and 30 nucleotides upstream of their RNA start sites. Single-base substitutions of the G8R promoter revealed two critical elements located from -26 to -13 (the core element) and -1 to +3 (the initiator element). Mutations in these regions drastically affected expression, as determined by beta-galactosidase and mRNA analyses. Additional mutations defined the TAAA sequence as the critical initiator element. The length, but not the nucleotide sequence, of the segment between the core and initiator regions was crucial. The requirement for the spacer to be 10 or 11 nucleotides was consistent with a single turn of a double helix. The A1L and A2L promoters resembled the G8R promoter, and mutations in the conserved bases had the predicted effects on expression. We concluded that the three intermediate promoters are composed of a 14-bp A+T-rich core sequence separated by one turn of the double helix from the TAAA initiator element. PMID- 1629952 TI - Deletion analysis of two tandemly arranged virulence genes in myxoma virus, M11L and myxoma growth factor. AB - Myxoma virus (MYX) is a leporipoxvirus of rabbits that induces a lethal syndrome characterized by disseminated tumorlike lesions, generalized immunosuppression, and secondary gram-negative bacterial infection. A MYX deletion mutant (vMYX-GF- delta M11L) was constructed to remove the entire myxoma growth factor (MGF) coding sequence and that for the C-terminal five amino acids of the partially overlapping upstream gene, M11L. Unexpectedly, this deletion completely abrogates the capacity of MYX to cause the characteristic disease symptoms of myxomatosis. Upon inoculation of rabbits with vMYX-GF- delta M11L, recipient animals developed only a benign, localized nodule reminiscent of a Shope fibroma virus-induced tumor in which a single primary lesion appeared at the site of injection and then completely regressed within 14 days, leaving the animals resistant to challenge with wild-type MYX. No evidence of the purulent conjunctivitis and rhinitis that always accompany wild-type MYX infection was observed. To ascertain whether the attenuation observed in vMYX-GF- delta M11L was due to a combined effect of the MGF deletion and alteration of the upstream M11L gene, two additional MYX recombinants were constructed: an MGF- virus (vMYX-GF-) containing an intact M11L gene and an M11L- virus (vMYX-M11L-) containing an intact MGF gene. Infection with vMYX-GF- resulted in moderated symptoms of myxomatosis, but all clinical stages of the disease were still detectable. In contrast, disruption of M11L alone dramatically reduced the virus virulence, resulting in a nonlethal syndrome whose clinical course was nevertheless distinct from that of vMYX-GF- delta M11L. Upon inoculation with vMYX-M11L-, rabbits developed primary and secondary tumors which were larger and more circumscribed than those of wild-type MYX recipients. Whereas wild-type MYX infection always includes severe, purulent conjunctivitis and rhinitis, vMYX-M11L- recipients remained healthy and displayed only minimal signs of respiratory distress. By about 30 days after infection, the tumors induced by vMYX-M11L- had completely regressed and these animals were immune to challenge with wild-type MYX. Histological analysis indicated that tumors induced by vMYX-M11L- are much more heavily infiltrated with macrophages and heterophils and that the sites of viral replication are more edematous and necrotic than those of wild-type infection, suggesting that the host was able to mount a more vigorous inflammatory response to vMYX-M11L- infection.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1629953 TI - Spike protein-nucleocapsid interactions drive the budding of alphaviruses. AB - Semliki Forest virus (SFV) particles are released from infected cells by budding of nucleocapsids through plasma membrane regions that are modified by virus spike proteins. The budding process was studied with recombinant SFV genomes which lacked the nucleocapsid protein gene or, alternatively, the spike genes. No subviral particles were released from cells which expressed only the nucleocapsid protein or the spike proteins. Virus release was found to be strictly dependent on the coexpression of the nucleocapsid and the spike proteins. These results provide direct proof for the hypothesis that the alphavirus budding is driven by nucleocapsid-spike interactions. The importance of the viral 42S RNA for virus assembly and budding was investigated by using the heterologous vaccinia virus-T7 expression system for the synthesis of the SFV structural proteins. The results demonstrate that the viral genome is not absolutely required for formation of budding competent nucleocapsids, since small amounts of viruslike particles were assembled in the absence of 42S RNA. PMID- 1629955 TI - Nucleotide sequence and transcriptional analysis of a gene encoding gp41, a structural glycoprotein of the baculovirus Autographa californica nuclear polyhedrosis virus. AB - We have identified and sequenced a region of the Autographa californica nuclear polyhedrosis virus (AcMNPV) genome encoding the major polyhedron-derived virus structural glycoprotein gp41. The open reading frame is located entirely within the AcMNPV SstII-M fragment. The protein sequence does not have hydrophobic regions characteristic of integral membrane proteins and contains a putative O linked GlcNAc glycosylation site. gp41 is expressed as a late gene, with transcripts starting within two consensus late transcription start sites (TAAG) located immediately upstream of the first methionine codon. A major transcription termination signal is bypassed, possibly generating a bicistronic message. Finally, the nucleotide and protein sequences of AcMNPV and Bombyx mori nuclear polyhedrosis virus are highly conserved. PMID- 1629954 TI - Mutations in the leucine zipper of the human immunodeficiency virus type 1 transmembrane glycoprotein affect fusion and infectivity. AB - Many retroviruses, including the human and simian immunodeficiency viruses, contain a leucine zipper-like repeat in a highly conserved region of the external domain of the transmembrane (TM) glycoprotein. This region has been postulated to play a role in stabilizing the oligomeric form of these molecules. To determine what role this region might play in envelope structure and function, several mutations were engineered into the middle isoleucine of the leucine zipper-like repeat of the human immunodeficiency virus type 1 (HIV-1) TM protein. A phenotypic analysis of these mutants demonstrated that conservative mutations (Ile to Val or Leu) did not block the ability of the viral glycoprotein to mediate cell-cell fusion or affect virus infectivity. In contrast, each of the other mutations, except for the Ile-to-Ala change, completely inhibited the ability of the glycoprotein to fuse HeLa-T4 cells and of mutant virions to infect H9 cells. The alanine mutation produced an intermediate phenotype in which both cell fusion and infectivity were significantly reduced. Thus, the biological activity of the glycoprotein titrates with the hydrophobicity of the residue in this position. None of the mutations affected the synthesis, oligomer formation, transport, or processing of the HIV glycoprotein complex. Although these results do not rule out a role for the leucine zipper region in glycoprotein oligomerization, they clearly point to a critical role for it in a post-CD4 binding step in HIV membrane fusion and virus entry. PMID- 1629956 TI - Complementation of murine cells for human immunodeficiency virus envelope/CD4 mediated fusion in human/murine heterokaryons. AB - Murine cell lines expressing human CD4 are resistant to the fusogenic effect of the human immunodeficiency virus (HIV) envelope. Consequently, they cannot be infected by HIV or form syncytia with HIV envelope-expressing cells. Murine cells could either lack human-specific cofactors necessary for the CD4/envelope mediated membrane fusion or express inhibitors of this process. To address this question, we have tested the ability of heterokaryons made from CD4-expressing murine cells and human cells to undergo HIV envelope-mediated fusion. We have devised a rapid and specific assay based on the induction of lacZ expression, in which membrane fusion events with HIV-infected cells can be detected by a simple histochemical technique. CD4-positive murine/human heterokaryons, but not murine/simian heterokaryons, were found able to fuse with HIV envelope-expressing cells. In these experiments, the fusion resistant phenotype of murine-CD4 cells could be complemented by human cellular factors. PMID- 1629957 TI - Role of TAR RNA splicing in translational regulation of simian immunodeficiency virus from rhesus macaques. AB - The untranslated leader sequences of rhesus macaque simian immunodeficiency virus mRNAs form a stable secondary structure, TAR. This structure can be modified by RNA splicing. In this study, the role of TAR splicing in virus replication was investigated. The proportion of viral RNAs containing a spliced TAR structure is high early after infection and decreases at later times. Moreover, proviruses containing mutations which prevent TAR splicing are significantly delayed in replication. These mutant viruses require approximately 20 days to achieve half maximal virus production, in contrast to wild-type viruses, which require approximately 8 days. We attribute this delay to the inefficient translation of unspliced-TAR-containing mRNAs. The molecular basis for this translational effect was examined in in vitro assays. We found that spliced-TAR-containing mRNAs were translated up to 8.5 times more efficiently than were similar mRNAs containing an unspliced TAR leader. Furthermore, these spliced-TAR-containing mRNAs were more efficiently associated with ribosomes. We postulate that the level of TAR splicing provides a balance for the optimal expression of both viral proteins and genomic RNA and therefore ultimately controls the production of infectious virions. PMID- 1629958 TI - Assembly of recombinant human immunodeficiency virus type 1 capsid protein in vitro. AB - The capsid protein (CA) (p24) of human immunodeficiency virus (HIV) type 1 expressed in Escherichia coli and purified to greater than 90% homogeneity was used to examine assembly in vitro and to probe the nature of interactions involved in the formation of capsid structures. The protein was detected in dimeric and oligomeric forms as indicated by molecular size measurements by gel filtration column chromatography, sedimentation through sucrose, and nondenaturing gel electrophoresis. Chemical cross-linking of CA molecules was observed with several homobifunctional reagents. Oligomer size was dependent on cross-linker concentration and exhibited a nonrandom pattern in which dimers and tetramers were more abundant than trimers and pentamers. Oligomers as large as dodecamers were detected in native polyacrylamide gels. These were stable in solutions of high ionic strength or in the presence of nonionic detergent, indicating that strong interactions were involved in oligomer stabilization. Limited tryptic digestion converted the putative dodecamers to octamers, suggesting that a region involved in CA protein multimerization was exposed in the structure. This region was mapped to the central portion of the protein. The recombinant CA proteins assembled in vitro into long rodlike structures and were disassembled into small irregular spheres by alterations in ionic strength and pH. The observation that assembly and disassembly of purified HIV type 1 CA protein can be induced in vitro suggests an approach for identifying possible control mechanisms involved in HIV viral core assembly. PMID- 1629959 TI - Nucleotide sequence of the jaagsiekte retrovirus, an exogenous and endogenous type D and B retrovirus of sheep and goats. AB - The complete genome of the jaagsiekte sheep retrovirus (JSRV), the suspected etiological agent of ovine pulmonary carcinoma, has been cloned from viral particles secreted in lung exudates of affected animals and sequenced. The genome is 7,462 nucleotides long and exhibits a genetic organization characteristic of the type B and D oncoviruses. Comparison of the amino acid sequences of JSRV proteins with those of other retrovirus proteins and phylogenetic studies suggest that JSRV diverged from its type B and D lineage after the type B mouse mammary tumor virus but before the type D oncoviruses captured the env gene of a reticuloendotheliosislike virus. Southern blot studies show that closely related sequences are present in sheep and goat normal genomic DNA, indicating that JSRV could be endogenous in ovine and caprine species. PMID- 1629960 TI - Intermonomer disulfide bonds impair the fusion activity of influenza virus hemagglutinin. AB - At a low pH, the influenza virus hemagglutinin (HA) undergoes conformational changes that promote membrane fusion. While the critical role of fusion peptide release from the trimer interface has been demonstrated previously, the role of globular head dissociation in the overall fusion mechanism remains unclear. To investigate this question, we have analyzed in detail the fusion activity and low pH-induced conformational changes of a mutant, Cys-HA, in which the globular head domains are locked together by engineered intermonomer disulfide bonds (L. Godley, J. Pfeifer, D. Steinhauer, B. Ely, G. Shaw, R. Kaufmann, E. Suchanek, C. Pabo, J. J. Skehel, D. C. Wiley, and S. Wharton, Cell 68:635-645, 1992). In this paper, we show that Cys-HA expressed on the cell surface is predominantly a disulfide-bonded trimer. Cell surface Cys-HA is impaired in its membrane fusion activity, as demonstrated by both content-mixing and lipid-mixing fusion assays. It is also impaired in its ability to change conformation at a low pH, as assessed by proteinase K sensitivity. The fusion activity and low pH-induced conformational changes of cell surface Cys-HA are, however, restored to nearly wild-type levels upon reduction of the intermonomer disulfide bonds. By using a set of conformation-specific monoclonal and anti-peptide antibodies, we found that purified Cys-HA trimers are impaired in changes that occur in the globular head domain interface. In addition, changes that occur at a great distance from the engineered intermonomer disulfide bonds, notably release of the fusion peptides, are also impaired. Our results are discussed with respect to current views of the fusion-active conformation of the HA trimer. PMID- 1629961 TI - The matrix protein of human immunodeficiency virus type 1 is required for incorporation of viral envelope protein into mature virions. AB - Accumulating evidence suggests that the matrix (MA) protein of retroviruses plays a key role in virus assembly by directing the intracellular transport and membrane association of the Gag polyprotein. In this report, we show that the MA protein of human immunodeficiency virus type 1 is also critical for the incorporation of viral Env proteins into mature virions. Several deletions introduced in the MA domain (p17) of human immunodeficiency virus type 1 Gag polyprotein did not greatly affect the synthesis and processing of the Gag polyprotein or the formation of virions. Analysis of the viral proteins revealed normal levels of Gag and Pol proteins in these mutant virions, but the Env proteins, gp120 and gp41, were hardly detectable in the mutant virions. Our data suggest that an interaction between the viral Env protein and the MA domain of the Gag polyprotein is required for the selective incorporation of Env proteins during virus assembly. Such an interaction appears to be very sensitive to conformational changes in the MA domain, as five small deletions in two separate regions of p17 equally inhibited viral Env protein incorporation. Mutant viruses were not infectious in T cells. When mutant and wild-type DNAs were cotransfected into T cells, the replication of wild-type virus was also hindered. These results suggest that the incorporation of viral Env protein is a critical step for replication of retroviruses and can be a target for the design of antiviral strategies. PMID- 1629962 TI - Dependence of minus-strand synthesis on complete genomic packaging in the double stranded RNA bacteriophage phi 6. AB - Bacteriophage phi 6 has a segmented genome consisting of three pieces of double stranded RNA (dsRNA). The viral procapsid is the structure that packages plus strands, synthesizes the complementary negative strands to form dsRNA, and then transcribes dsRNA to form plus-strand message. The minus-strand synthesis of a particular genomic segment is dependent on prior packaging of the other segments. The 5' end of the plus strand is necessary and sufficient for packaging, while the normal 3' end is necessary for synthesis of the negative strand. We have now investigated the ability of truncated RNA segments which lack the normal 3' end of the molecules to stimulate the synthesis of minus strands of the other segments. Fragments missing the normal 3' ends were able to stimulate the minus strand synthesis of intact heterologous segments. Minus-strand synthesis of one intact segment could be stimulated by the presence of two truncated nonreplicating segments. The 5' fragments of each single-stranded genomic segment can compete with homologous full-length single-stranded genomic segments in minus strand synthesis reactions, suggesting that there is a specific binding site in the procapsid for each segment. PMID- 1629963 TI - A mutation at one end of Moloney murine leukemia virus DNA blocks cleavage of both ends by the viral integrase in vivo. AB - The integration of retroviral DNA proceeds through two steps: trimming of the termini to expose new 3' OH ends, and the transfer of those ends to the phosphates of target DNA. We have examined the ability of the Moloney murine leukemia virus integrase protein (IN) to trim the termini of the preintegrative DNA of mutant viruses with alterations in the U3 inverted repeat. The mutant terminus of one replication-defective viral DNA, containing a 7-bp deletion in the U3 inverted repeat, was not trimmed to produce the normal recessed end. Remarkably, the other terminus of this mutant DNA was also not trimmed, even though its sequence is wild type. This finding suggests that the IN protein requires the presence of two good ends before becoming properly activated to trim either one. PMID- 1629964 TI - Rabies virus neuritic paralysis: immunopathogenesis of nonfatal paralytic rabies. AB - Two pathogenetically distinct disease manifestations are distinguished in a murine model of primary rabies virus infection with the Evelyn-Rokitnicky Abelseth strain, rabies virus neuritic paralysis (RVNP) and fatal encephalopathogenic rabies. RVNP develops with high incidence in immunocompetent mice after intraplantar infection as a flaccid paralysis restricted to the infected limb. The histopathologic correlate of this monoplegia is a degeneration of the myelinated motor neurons of the peripheral nerve involved. While, in this model, fatal encephalopathogenic rabies develops only after depletion of the CD4 subset of T lymphocytes and without contribution of the CD8 subset, RVNP is identified as an immunopathological process in which both the CD4 and CD8 subsets of T lymphocytes are critically implicated. PMID- 1629965 TI - Alphavirus spike-nucleocapsid interaction and network antibodies. AB - Vaux et al. (D. J. T. Vaux, A. Helenius, and I. Mellman, Nature (London) 336:36 42, 1988) recently reported the production of network antibodies that were suggested to have reconstructed a specific interaction between the nucleocapsid of Semliki Forest virus and the cytoplasmic tail of the viral E2 spike protein. The F13 anti-idiotype antibody, which was raised against anti-E2 tail antibodies, was claimed to recognize the virus nucleocapsid. In this report, we have used recombinant SFV viruses to demonstrate that the F13 antibody is not nucleocapsid specific but instead most likely recognizes some component of the viral replication machinery. PMID- 1629966 TI - Functional tolerance of the human immunodeficiency virus type 1 envelope signal peptide to mutations in the amino-terminal and hydrophobic regions. AB - We demonstrated that the leader sequence of the human immunodeficiency virus type 1 envelope functions as signal peptide (SP) despite low scoring in a prediction program. As expected for SP, the hydrophobic core (HC) is essential, and no other sequence could compensate for HC deletion. Contrary to other SPs, major substitutions in the HC, such as introduction of basic, polar, or alpha-helix breaking residues, still allowed efficient translocation and glycosylation. Also, extensive deletions or substitutions of the charged residues at the N terminus had little if any inhibitory effect. This report, which is the first study of human immunodeficiency virus SP, describes the exceptional tolerance of this peptide to mutations. PMID- 1629967 TI - Envelope glycoprotein and CD4 independence of vpu-facilitated human immunodeficiency virus type 1 capsid export. AB - The effect of vpu on the release of human immunodeficiency type 1 capsid proteins was examined in the presence or absence of virus-encoded envelope glycoproteins as well as in cells which constitutively express either the CD4 or CD8 protein. The results show that vpu-mediated facilitated export of capsid proteins from HeLa cells does not require expression of the envelope glycoprotein. The experiments also show that export of virus capsid proteins from HeLa cells facilitated by vpu is not affected by coexpression of either the CD4 or CD8 protein. The vpu protein acts in trans to facilitate export of virus capsid proteins from HeLa cells. PMID- 1629968 TI - Bipartite signal for read-through suppression in murine leukemia virus mRNA: an eight-nucleotide purine-rich sequence immediately downstream of the gag termination codon followed by an RNA pseudoknot. AB - The pol gene of murine leukemia virus and other mammalian type C retroviruses is expressed by read-through suppression of an in-frame UAG codon which separates the gag and pol coding regions. In this study, we have analyzed the sequence requirements for read-through suppression by placing different portions of wild type and mutant viral sequences from the gag-pol junction between reporter genes and testing transcripts of these constructs for suppression in reticulocyte lysates. We find that the read-through signal is contained within the first 57 nucleotides on the 3' side of the UAG codon. Our results indicate that the identities of six conserved bases in the eight-nucleotide, purine-rich sequence immediately downstream of the UAG codon are critical for suppression, as is the existence of a pseudoknot structure spanning the next 49 nucleotides. Thus, read through suppression depends on a complex, bipartite signal in the mRNA. PMID- 1629969 TI - Determinants of thymotropism in Kaplan radiation leukemia virus and nucleotide sequence of its envelope region. AB - Radiation leukemia viruses (RadLVs) are a group of murine leukemia viruses which are induced by radiation and cause T-cell leukemia. Viral clones isolated from the BL/VL3 lymphoid cell line derived from a thymoma show variable tropism and leukemogenic potential. We have constructed chimeric viruses by in vitro recombination between two viruses, a RadLV that is thymotropic and an endogenous ecotropic virus that is nonthymotropic. We show here that, in contrast to thymotropism determinants identified previously, which lie in the long terminal repeat (LTR), it is the envelope region that is responsible for the thymotropism of BL/VL3 RadLV. The nonthymotropic virus which we have rendered thymotropic by transfer of the env region of RadLV in the present study has been shown previously to become thymotropic when the LTR of another thymotropic virus is inserted in its genome. Thus, the LTR and envelope gene may be involved in complementary action to lead to thymotropism. PMID- 1629970 TI - Genetic assay for multimerization of retroviral gag polyproteins. AB - We have established a genetic assay for the multimerization of retroviral gag polyproteins. This assay is based on the GAL4 two-hybrid system for studying protein-protein interactions (S. Fields and O. Song, Nature (London) 340:245-246, 1989). In our initial experiments, we generated Saccharomyces cerevisiae plasmids that separately express the GAL4 DNA-binding and GAL4 activation domains fused to the human immunodeficiency virus type 1 (HIV-1) gag polyprotein, Pr55gag. The coexpression of these two hybrid proteins in S. cerevisiae results in the association of the GAL4 domains and the potent activation of an integrated GAL4 responsive lacZ indicator gene. Similar results were obtained with plasmids encoding GAL4-Moloney murine leukemia virus (M-MuLV) gag polyprotein hybrid proteins. In contrast, the heterologous GAL4-HIV-1 gag and GAL4-M-MuLV gag fusion proteins were unable to interact with each other to induce lacZ expression. The results suggest that this yeast system provides a rapid and specific assay for the interactions of retroviral gag proteins that occur during virion assembly. PMID- 1629971 TI - Variant-specific monoclonal and group-specific polyclonal human immunodeficiency virus type 1 neutralizing antibodies raised with synthetic peptides from the gp120 third variable domain. PMID- 1629972 TI - Museum scholars to apply Holocaust experience to 1990s biomedical issues. PMID- 1629973 TI - Two years after Iraqi invasion, US Military medicine studies Desert Shield/Storm while looking ahead. PMID- 1629974 TI - Declaration has health message for politicians. PMID- 1629975 TI - Game's afoot in many lands for forensic scientists investigating most-extreme human rights abuses. PMID- 1629976 TI - Torture survivors find helping hands worldwide. PMID- 1629977 TI - Health professionals persecuted in violation of their human rights: a partial list of cases. PMID- 1629978 TI - Diagnosing streptococcal pharyngitis. PMID- 1629979 TI - Optimizing growth potential of children. PMID- 1629980 TI - Progressive multifocal leukoencephalopathy following treatment for Wegener's granulomatosis. PMID- 1629981 TI - Health care workers infected with human immunodeficiency virus. PMID- 1629982 TI - Disease in adopted children from Romania. PMID- 1629983 TI - Academic boycott of South Africa. PMID- 1629984 TI - Perplexing parlance of paraneoplastic pemphigus. PMID- 1629985 TI - Cool question: warm reply. PMID- 1629986 TI - Just reach out and percuss someone. PMID- 1629987 TI - Racial differences in coronary artery bypass rates. PMID- 1629988 TI - Psychiatric implications of missile attacks on a civilian population. Israeli lessons from the Persian Gulf War. AB - OBJECTIVE: To determine the proportion of hospitalized patients who had stress reactions as a result of missile attacks during the Persian Gulf War and evaluate the factors that influenced their evacuation. DESIGN: Review of medical records of patients hospitalized as a result of missile attacks. SETTING: During the Persian Gulf War in the winter of 1991, Israel received 18 missile attacks involving 39 surface-to-surface Scud missiles. The uncertainty in time, place, and type of warhead, conventional or chemical, was a source of chronic stress and the immediate cause for many traumatic stress reactions at or near the missile attack sites. PARTICIPANTS: Data from victims who were injured after each missile attack were available through a central hookup between 12 local hospitals and the Medical Corps of the Israeli Defence Force. MAIN OUTCOME MEASURE: The number of persons diagnosed in the hospital as psychological casualties after each missile attack. RESULTS: Approximately 43% of the 773 casualties evacuated to hospitals were diagnosed as psychological casualties, and an additional 27% had mistakenly injected themselves with atropine. Data also indicated that triage of psychological casualties to hospitals was more a function of the rescue team's training and preparation than the severity or extent of injury or damage. CONCLUSIONS: Optimal treatment during events that cause mass casualties requires proper preparation of rescue teams as well as reorganization of the hospital's psychiatric services. The threat of chemical warfare affected the number and nature of stress reactions. PMID- 1629989 TI - Thyroid nodules in the population living around Chernobyl. AB - OBJECTIVE: To determine the baseline incidence, prevalence, and characteristics of thyroid nodules in the population living around the Chernobyl nuclear power plant and to compare the findings with unexposed populations. DESIGN: Prevalence study. Population samples from seven highly contaminated villages were compared with six nearby control villages of the same size and type. The data were obtained as part of the International Chernobyl Project conducted in 1990. SETTING: The study was conducted 4.5 years after the Chernobyl reactor accident that released large quantities of radionuclides, including radioiodine. PATIENTS OR OTHER PARTICIPANTS: Population samples of approximately 100 persons residing in both highly contaminated villages and control villages since the accident were compared. Individuals were selected on the basis of birth date as being 5, 10, 40, or 60 years old at the time of the study. All persons selected underwent a thyroid examination. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Two main outcome measures were used, both for thyroid nodularity: clinical palpation and high resolution ultrasonography. RESULTS: There was no significant difference in thyroid nodularity between the study groups. Nodules were palpated in 0.7% of children and 2.9% of adults. Discrete nodules were found by ultrasonography in 0.5% of children and 14.9% of adults. Multinodular goiter was found in 3% of adults. Nodules were more common in females. CONCLUSIONS: Four and a half years after the Chernobyl accident, the incidence, prevalence, and characteristics of thyroid nodules were the same in population samples from both highly contaminated and control settlements and similar to results reported for unexposed populations in other countries. PMID- 1629990 TI - Estimation of radiation risks. BEIR V and its significance for medicine. PMID- 1629991 TI - Epidemiological and laboratory studies of power frequency electric and magnetic fields. PMID- 1629992 TI - Atropine poisoning in children during the Persian Gulf crisis. A national survey in Israel. AB - OBJECTIVE: To evaluate the effects of high doses of atropine in children accidentally injected with automatic atropine injectors. These were distributed in Israel during the Persian Gulf Crisis as an antidote for chemical warfare agents. DESIGN AND SETTING: A national survey in pediatric emergency departments in Israel, involving 22 medical centers, with prospective data collection in 14 centers. PATIENTS: Children (n = 268) presenting to emergency departments following misuse of automatic atropine injectors. MAIN OUTCOME MEASURES: Documentation of atropine dose and clinical manifestations; determination of a clinical severity score and its correlation with atropine dose; measurements of serum atropine levels in six patients. RESULTS: Over a period of 4 months, 268 cases were reported, of which 240 were clinically evaluated. The most common site of injection (75%) was the finger or palm. Doses were up to 17-fold higher than standard doses for age. In 116 children (48%), systemic effects of atropine were observed, and 20 (8%) had severe atropinization. Seizures and life-threatening arrhythmias were not reported, and there were no fatalities. The severity of atropinization was correlated with the dose following a classic nonlinear, dose response relationship. Serum atropine levels (6.2 to 61.0 ng/mL) were much higher than those observed after administration of therapeutic doses. CONCLUSIONS: The high incidence of injection in the hand implies accidental use of automatic atropine injectors among children. The lack of mortality or life-threatening complications from injection of large doses of atropine attests to its relative safety in children. The low risk from atropine injections weighed against expected benefit as a lifesaving antidote justifies the distribution of personal atropine injectors to children at risk of organophosphorus nerve agent attack. PMID- 1629993 TI - Efficacy of treatments for posttraumatic stress disorder. An empirical review. AB - OBJECTIVE--The purpose of this article is to review the empirical evidence for the efficacy of a range of treatments for posttraumatic stress disorder (PTSD). Reviewed studies focused on rape victims, combat veterans, the tragically bereaved, torture victims, accident victims, of physical assault, and child abuse victims. DATA SOURCES--Peer-reviewed journals (Psych-Info, MEDLINE), book chapters (PILOTS database), active investigators, abstracts from the 1990 and 1991 International Society for Traumatic Stress Studies. STUDY SELECTION--We identified 255 English-language reports of treatment for PTSD. We restricted our focus to randomized, clinical trials that included a systematic assessment of PTSD using DSM-III or DSM-III-R criteria (N = 11). DATA EXTRACTION--Studies were assessed according to methodological strength: random assignment to the treatment of interest, and either an alternative treatment or control group; sample selection; and inclusion of statistical tests of significance. DATA SYNTHESIS- Drug studies show a modest but clinically meaningful effect on PTSD. Stronger effects were found for behavioral techniques involving direct therapeutic exposure, particularly in terms of reducing PTSD intrusive symptoms. However, severe complications have also been reported from the use of these techniques in patients suffering from other psychiatric disorders. Studies of cognitive therapy, psychodynamic therapy, and hypnosis suggest that these approaches may also hold promise. However, further research is needed before any of these approaches can be pronounced effective as lasting treatment of PTSD. CONCLUSIONS- Further studies should specifically address combined treatment approaches, optimal treatment length and timing, effects of comorbidity, and unstudied traumatized populations. PMID- 1629994 TI - Electromagnetic pulse and its effects. Board of Trustees, American Medical Association. PMID- 1629995 TI - Children and childhoods. Hidden casualties of war and civil unrest. PMID- 1629996 TI - Thyroid hormones in liver disease. PMID- 1629997 TI - Thyroid hormone levels in hepatitis B. AB - Thyroid hormone levels were estimated in fifty patients with hepatitis B. In acute phase, T3 was raised in 10% and T4 in 60%. This rise was directly proportional to the transaminases levels. Twenty cases were also studied in the recovery phase where thyroid hormones returned to within normal limits. This rise of T3 and T4 in acute phase is attributed to increased thyroxin binding capacity due to release of thyroid binding globulin into circulation from necrosing hepatocytes. PMID- 1629998 TI - Risk factors for depression. AB - The role of social factors in the causation of depression based on the aetiological model proposed by Brown and Harris was examined in a sample of 50 depressed female patients. Loss of mother before age 11 years and lack of confiding relationship was found to act as a vulnerability factor whereas employment status and having three or more children aged 14 or under were not found to have an increased vulnerability in these patients. These results which provide general support for Brown and Harris's causal model are discussed with their possible implications in our socio-cultural settings. PMID- 1629999 TI - Glycaemic index of Pakistani staple foods in mixed meals for diabetics. AB - Glycaemic index of local staple foods was determined. In first phase, the post prandial blood glucose response of isocaloric portion of wheat chapati and gram flour (baisen) chapati, were compared in 11 type II diabetic patients as a part of mixed meal in fasting state, alternately. The glycaemic index of baisen chapati was 39 as compared with wheat chapati. In second phase of the study, 22 type II diabetic patients were given isocaloric portions of wheat chapati and boiled rice as a part of mixed meal alternately. The glycaemic index of rice was 98 as compared with wheat chapati. This study favours the belief that baisen chapati is better and refutes that rice is bad for diabetics. It also upholds that glycaemic index is useful for planning a diabetic diet. PMID- 1630000 TI - Prognostic factors in ganglionic and thalamic haemorrhages: a clinical and radiological study. AB - Clinical and radiological features of 43 patients admitted for ganglionic (21) and thalamic (22) haemorrhages were studied to ascertain the factors that would determine prognosis in the acute stage of the illness. Nineteen patients died, 16 of them in the first week. The adverse clinical factors were an altered state of consciousness, decorticate/decerebrate posturing, ataxic respiration, abnormalities of gaze and presence of bilateral Babinski's sign. Adverse radiological factors were the presence of thalamic haemorrhage of 3 cm or more, intraventricular spread of the haemorrhage and midline shift of 0.5 cm of more. The significance of these findings is discussed. PMID- 1630001 TI - Estimation and separation of N-acetyl-beta-D-glucosaminidase isoenzymes in urine. AB - N-acetyl-beta-D-glucosaminidase is a lysosomal enzyme made up of two isoenzymes (A and B). It has been used extensively as a marker for kidney damage. However, its estimation in urine has not been standardized. We have established a method for the estimation and separation of NAG isoenzymes by ion-exchange chromatography. In 19 experiments done so far, this method has given reproducible results. The significance of this method is that with a single experiment, one can estimate total as well as individual isoenzyme activity. Furthermore, urine constituents do not appear to interfere in this assay. PMID- 1630002 TI - Family medicine postgraduate training in Pakistan. AB - There is no organized system of postgraduate training for family medicine or general practice in Pakistan. This paper describes the status of primary health care delivery in Pakistan and the growth of family medicine throughout the world. It stresses the need for organized postgraduate training relevant to the needs of primary health care in Pakistan and describes efforts currently under-way in this regard at the Aga Khan University Medical Centre (AKUMC) in collaboration with the College of Physicians and Surgeons of Pakistan. PMID- 1630003 TI - Abdominal complications of ascaris lumbricoides in children. PMID- 1630004 TI - Congenital generalized lipodystrophy. PMID- 1630005 TI - An unusual presentation of ischiorectal abscess. PMID- 1630006 TI - [Fundamentals of leukemia differentiation therapy]. PMID- 1630007 TI - [Regulation of eosinophilopoiesis]. PMID- 1630008 TI - [Neutrophil dysfunction]. PMID- 1630009 TI - [Post-transfusion graft-versus-host disease]. PMID- 1630010 TI - [Chemotherapy and FAB classification]. PMID- 1630011 TI - [Cytogenetics and FAB classification]. PMID- 1630012 TI - [Molecular biology and FAB classification]. PMID- 1630013 TI - [Megakaryocyte differentiation factor isolated from cultured undifferentiated thyroid carcinoma supernatant--activin's biological activity]. PMID- 1630014 TI - [Megakaryocyte-platelet hematopoietic factor produced by human lung cancer cell line (MC-1)]. PMID- 1630015 TI - [The effect of vascular endothelial cells on the maturation of megakaryocytes]. PMID- 1630016 TI - [Clinical and molecular biological study of Ph positive acute leukemia: comparison with blast crisis of chronic myelogenous leukemia and Ph negative acute lymphoblastic leukemia]. AB - Eight cases of Philadelphia positive acute leukemia (Ph+AL) were compared with 13 cases of Ph+ chronic myelogenous leukemia in blast crisis (BC) and 10 cases of Ph negative acute lymphoblastic leukemia (Ph-ALL) based on the clinical and molecular biological findings. Distinguishing clinical features were a high leukocyte count (median; 147.9 x 10(3)/microliters) for Ph+AL, and a high incidence of tumor formation and basophilia for BC. A cytogenetic study demonstrated the disappearance or marked reduction of Ph+ metaphases in Ph+AL in remission, while Ph+ cells persisted in BC. The major bcr gene was not rearranged in 4 Ph+AL cases, whereas it was found rearranged in 4 other cases of Ph+ AL and 6 cases of BC. Reverse transcriptase polymerase chain reaction technique demonstrated the presence of minor bcr/abl mRNA in the former three cases, and major bcr/abl mRNA in the latter 4 cases. Remission rates were 63% for Ph+AL, 38% for BC, and 100% for Ph-ALL, and the 50% survival were 12, 5 and 29 months, respectively. It was concluded that Ph+AL can be differentiated from BC by a marked reduction of Ph+ cells at remission, and that the prognosis of Ph+AL is better than BC, but worse than Ph-ALL. PMID- 1630017 TI - [Study on the therapy of multiple myelomas--initial induction therapy (MP, IFN alpha, steroid pulse) and maintenance therapy (VMP, MP continuous, VEP, MCNU)]. AB - Untreated twenty patients of multiple myeloma were treated with the chemotherapy protocol as follows: Initial induction therapy;MP continuous or MP intermittent-- -IFN alpha----steroid pulse. Maintenance therapy;alkylating agents which have no cross resistance were used ((V) MP----(MP)----(V) EP----MCNU). Remission rate (CR+PR) after the initial MP therapy was 45%, and that after including IFN alpha and steroid pulse therapy was 50%, Fifty percent survival rate was almost as same as those reported previously (34M). Our protocol presented here was based on the idea that, initially, myeloma cells with proliferative activity could be affected by MP therapy, and subsequent IFN alpha therapy would have effect even on the residual myeloma cells. Serial checks of 3H-TdR uptake of myeloma cells during the therapy supported this idea. During the maintenance therapy, clinical responses to the initial induction therapy were not aggravated in the responded cases when evaluated by the variation of serum M-protein level. We propose that considering from a point of proliferative activity of myeloma cells is important for designing therapeutic protocols for multiple myeloma. PMID- 1630018 TI - [The significance of myelodysplasia in untreated patients with multiple myeloma]. AB - Microscopic analysis of bone marrow smears from ten untreated patients with multiple myeloma (MM) revealed that seven patients had myelodysplastic changes. Of these, five patients had anemia alone while the other two had anemia and leucopenia. The myelodysplastic changes seen in MM were less extensive than those seen in myelodysplastic syndrome (MDS). Moreover, the dysplastic changes in MM were determined to be limited to two or three lineage cells. Dysplastic changes were observed even after clinical signs of MM had improved due to therapy. We consider that the myelodysplastic changes seen in MM can be attributed to MM itself, rather than to the coexistence of MDS and MM. Such findings suggest that the pathogenesis of MM involves a common stem cell which differentiates into multiple lineage cells. PMID- 1630020 TI - [Chronic myelomonocytic leukemia associated with translocation 1;7, marked platelet aggregation and cryofibrinogenemia: a case report]. AB - A 64-year-old male was admitted in September 1989 with complaints of fever and muscular weakness in the extremities. A peripheral blood examination on admission revealed WBC 10,300/microliters (monocytes 32%), RBC 195 x 10(4)/microliters, Hb 7.9 g/dl, Plt 12.8 x 10(4)/microliters with trilineage dysplasia. Bone marrow biopsy was normoplastic marrow with 25.7% of monocytes including immature blasts. Cytochemical analysis of the monocytes showed positive for peroxidase and dual esterase staining. Chromosomal analysis of peripheral blood revealed 46, XY, -7, +der(1) t(1;7)(p11;p11). A diagnosis of chronic myelomonocytic leukemia was made. Hemostatic studies revealed cryofibrinogenemia, marked platelet aggregation on blood smear, hyperfibrinogenemia and a marked increase in maximal amplitude of thrombelastogram. Treatment with prednisolone and VP16, resulted in a reduction of peripheral monocytes and a disappearance of cryofibrinogen, marked platelet aggregation and a decrease in muscular weakness. Nine months after diagnosis he died of DIC, pneumonia, lung abscess and sepsis. PMID- 1630019 TI - [Multiple myeloma in a patient in remission from malignant lymphoma]. AB - A 71-year-old man was admitted because of right cervical lymph node swelling in February 1986. Lymph node biopsy revealed that he suffered from diffuse, large cell malignant lymphoma. Immunological staining showed lymphoma characterized by B cell markers, IgG, kappa type. Bone marrow aspiration, revealed no evidence of lymphoma and 0.2% plasma cells. The clinical stage was IIA. The patient was treated with the CHOP regimen (doxorubicin, cyclophosphamide, vincristine and prednisolone), which achieved complete remission. In October 1988, he was re admitted because of a subcutaneous abscess, and biopsy of the inguinal lymph node showed reactive lymphadenitis. Although he improved with antibiotic therapy, laboratory date on admission showed monoclonal gammopathy. Serum immunoelectrophoresis demonstrated a monoclonal bow of IgA kappa type, and bone marrow aspiration revealed hypercellularity with an increased number of plasma cells (76.8%). The patient was diagnosed as having multiple myeloma, and combination chemotherapy was begun. He now attends the out-patient department at our hospital. The development of multiple myeloma has not been reported previously during a course of malignant lymphoma. Although the association of these two B cell neoplasias was unknown, in this case both showed the characteristic of kappa type light chains. This case may provide information concerning tumor cell origin. PMID- 1630021 TI - [Isospora belli infection in a patient with adult T-cell leukemia]. AB - An adult T cell leukemia (ATL) accompanied with Isospora belli infection was described. A 65-year-old male was admitted to our hospital because of a two month history of watery diarrhea. On admission, physical examination showed slight pallor but no detectable superficial lymphadenopathies. Hepatosplenomegaly was not observed. Laboratory examination revealed a leukocyte count 5,500/microliters with 10% abnormal lymphoid cells. A majority of the abnormal lymphoid cells expressed both CD 4 and CD 8 antigens. The patient was diagnosed as chronic ATL, since anti-HTLV-1 antibody in his serum and monoclonal integration of HTLV-1 proviral DNA in his peripheral mononuclear cells were detected. Isospora belli was found in his feces thereafter, and trimethoprim/sulfamethoxazole was effective for diarrhea. In Japan, there have been only 9 reported cases of lymphoproliferative disorders (including five ATL patients) accompanied with Isospora belli infection. From the descriptions in those reports, these 9 cases might all be ATL patients. PMID- 1630022 TI - [Post-gastrectomized vitamin B12 deficient anemia with marked leukoerythroblastosis and ringed sideroblasts]. AB - A 77 year-old man, who had received total gastrectomy and splenectomy 11 years ago for gastric cancer was transferred to our hospital because of severe macrocytic anemia. He had been treated with vitamin B1, B2, C and iron preparations for several weeks. Ten days before admission numbness developed in his legs. On physical examination he appeared severely anemic. Laboratory findings revealed severe macrocytic anemia with poikilocytosis, anisocytosis, polychromasia, red cell fragmentation, Howell-Jolly bodies, Cabot rings and marked erythroblastosis (421/100 WBC). Hypersegmented neutrophils and immature granulocytes were also seen in the blood. The bone marrow picture showed marked erythroid hyperplasia, but erythroblasts revealed only slight megaloblastic changes. On bone marrow iron staining all erythroblasts were classified as type III sideroblasts and 15% of them were ringed-form. Serum vitamin B12 was low (44 pg/ml). Methylcobalamin given intramuscularly led to the rapid improvement of all hematological abnormalities including leukoerythroblastosis. Two weeks after vitamin B12 administration, ringed sideroblasts could no longer be detected in the bone marrow. Post-gastrectomy vitamin B12 deficiency anemias combined with erythroblastosis and ringed sideroblasts is a rare condition. Splenectomy is thought to play an important role in the pathogenesis of these conditions. PMID- 1630023 TI - [i(17q) appearing in acute phase in Ph1-negative, BCR-negative CML]. AB - A 36-year-old woman was referred to our hospital because of splenomegaly in February 1989. The leukocyte count was 55,500/microliter without hiatus leukemicus. The leukocyte alkaline phosphatase score was low (29). The bone marrow showed myeloid hyperplasia (24.8% myeloblasts) but no dysplastic change. The karyotype of the bone marrow cells was 46, XX and a diagnosis of Ph1 (-) CML was made. Treatment with VCR, 6MP and prednisolone made 7-month duration chronic phase, but the abnormal karyotype.[46, XX, i(17q)] gradually increased to 100% of bone marrow cells. The patient died in June 1990. The evidence that not only a BCR rearrangement but also messages of BCR/ABL fusion gene were negative made us able to differentiate this case from Ph1(-), BCR(+) CML. The addition of an i(17q) results in partial monosomy of 17q (17q13;p53 gene) and partial trisomy of 17q (17q11.2-12;G-CSF gene). We examined the rearrangement of p53 gene and G-CSF dependent tumor cell growth in vitro, demonstrating one allelic loss of p53 gene and independent cell growth on G-CSF respectively. It is thought that in Ph1 (-), BCR (-) CML as well as in Ph1 (+) CML, an i(17q) is related to the progression but not to the initiation of these leukemias. However the precise mechanism, including p53 gene inactivation by point mutation, is still to be elucidated. PMID- 1630025 TI - [CML with autoimmune thrombocytopenia observed in the course of IgG (kappa) type monoclonal gammopathy]. AB - An 80-year-old male with IgG (kappa) type benign monoclonal gammopathy was admitted to our hospital because of marked leukocytosis. At the time of admission, thrombocytopenia was also noted. A bone marrow aspirate showed marked granulocytosis with a normal megakaryocyte count. PAIgG was elevated and the NAP score was low. Ph1 chromosome and rearrangement of the breakpoint cluster region were detected. On the basis of these findings, he was diagnosed as having CML with autoimmune thrombocytopenia. This case was of interest with respect to blood cell differentiation and immunological findings. PMID- 1630024 TI - [Neutrophilic dermatosis in a patient with refractory anemia]. AB - A 46-year-old man diagnosed as refractory anemia was hospitalized because of high fever and extensive erythema with ulceration in the femoral region. His peripheral blood examination showed marked leukocytosis (WBC 31,500/microliter:neutrophilic 90%) and anemia (Hb 8.6 g/dl. In spite of administration of antibiotics, the cutaneous ulcer rapidly extended to the right thigh and became necrotic. The bacterial culture of the cutaneous lesion showed no growth and a skin biopsy showed infiltration of neutrophils in the dermis. He became afebrile and his cutaneous lesion improved after administration of corticosteroid. When the dose of corticosteroid was decreased, cutaneous erythema and nodules appeared at other sites repeatedly, and disappeared after the dose of corticosteroid was increased. The cutaneous lesions had characteristics of both Sweet's syndrome and pyoderma gangrenosum. Moreover, the patient had immunological abnormalities and decreased neutrophilic functions (chemotaxis and O2- generation). Thus, it was suggested that the cutaneous lesions of this patient could be diagnosed as "neutrophilic dermatosis of MDS", and corticosteroid was recognized to be very effective in treating these skin lesions. PMID- 1630026 TI - [Effect of vasopressin on phospholipid metabolism in cultured rat mesangial cells]. AB - Aqueous solutions containing extracts of cultured rat mesangial cells treated with and without arginine vasopressin (AVP) were measured by phosphorus-31 nuclear magnetic resonance spectroscopy (31P-NMR). Ratios of the NMR signal intensities of phospholipids in the solutions were calculated with the areas of those resonance lines. Furthermore, prostaglandin E2 (PGE2) production and incorporation of 3H-methyl group into phospholipids in mesangial cells were observed in the presence and in the absence of AVP. We examined the role of AVP in the phospholipid metabolism of mesangial cells by the results from these three kinds of experiments. Ratios of (phosphorylcholine + glycerophosphorylcholine)/(phosphorylethanolamine + glycerophosphorylethanolamine), (PC + GPC)/(PE + GPE), and PC/PE increased significantly 5 min after AVP administration. Ratios of (GPE + GPC)/(PE + PC) and GPE/PE also increased significantly 30 min and 60 min after administration of AVP. The production of PGE2 increased with AVP treatment. This increment was inhibited with mepacrine and Adenosyl-S-isobutyl mercaptan (SIBA). Incorporation of 3H-methyl group into cellular phospholipids was accelerated with AVP, and then the resolution of methylated phospholipids and the release of PGE2 increased. These findings indicate that phospholipid methylation may be accelerated with AVP treatment and phosphatidylcholine, synthesized by transmethylation pathway, may be important as the substrate for PGE2 production in mesangial cells. PMID- 1630027 TI - [Charge distribution of serum IgA in IgA nephropathy with episodes of macrohematuria]. AB - In order to examine further the role of the electrical change of IgA in the pathogenesis of IgAN, we studied the charge distribution of serum IgA in IgAN with episodes of macrohematuria. Blood samples were taken from 20 IgAN patients during bouts of macrohematuria and again more than 3 months later. Twenty healthy adults were used as controls. All samples were focused by Multiphor II flatbet electrofocusing unit apparatus (LKB) on an agarose gel (0.8% isogel agarose-EF, 2.5% pharmalyte 4.0-6.5). The focused gels were incubated with polyclonal goat anti-human IgA and were washed in several changes of saline for 48 hours. Immunofixed materials remaining in the gels after washing were fixed and stained with coomassie brilliant blue R250. The stained gels were analysed by densitometry. The relative areas of the individual peaks and their proportional contributions to the total IgA spectrotype were determined by computer. The results were as follows: 1. The percentage of proportional contribution of IgA peaks (pI 4.7-5.15) in IgAN were higher in patients than in controls (p less than 0.01). 2. The percentage of proportional contribution of IgA peaks (pI 4.9-5.05) in IgAN at bouts of macrohematuria was higher than in the same patients when not undergoing episodes of macrohematuria (p less than 0.01). These results suggest that the excess amount of anionic IgA may contribute to the pathogenesis of IgAN. PMID- 1630029 TI - [Changes in size of adult renal allografts in pediatric recipients, clinicopathologic study of decreased graft size in infant recipients and hypertrophy, renal growth in older children]. AB - It is presumed that graft size after renal transplantation from adult donor decreases in infant or very young recipient and increases in older recipient. Measurement of graft length, width, parenchymal thickness on intravenous pyelography (IVP) films, measurement of area of Bowman's capsule, glomerulus, capillary tuft and tubule on graft biopsy specimens were compared between 3 months and 1 year after renal transplantation. The graft sizes decreased in recipients below 6 years-old or body height (Ht.) 90 cm and increased in recipients above 6 years-old, Ht. 100 cm. The case of decreased graft size was found a decrease of area of Bowman's capsule, glomerulus, capillary tuft and tubule. We suggest that it is caused by a difference between renal blood flow in infant and in adult. It is suggested that graft hypertrophy depends predominantly on increased tubular size and capillary tuft enlargement occurs prior to glomerular, tubular change. But, an increase in creatinine clearance (Ccr) was not found following graft hypertrophy. PMID- 1630028 TI - [Effect of oral adsorbent AST-120 in rats with chronic renal failure--mechanism of progression of renal failure by dietary protein]. AB - Progression of renal insufficiency was evaluated in partially nephrectomized Sprague-Dawley rats at the age of 10 weeks, fed on the low (6%), usual (20%), and high (36%) protein diet (group 6C, 20C, and 36C). Effects of oral adsorbent AST 120 on these experimental uremic models were also examined (group 6A, 20A, 36A). All the rats underwent paired feeding, and survived during the experimental period of 3 weeks. GFR (inulin clearance) and RPF (para-amino hippurate clearance), as well as Ccr was measured before the sacrifice. Initial serum creatinine and Ccr were 1.7 mg/dl and 0.27 ml/min. The rats of group 36C showed progressive elevation of serum creatinine level and decrease in Ccr. At the end of the study, GFR was significantly lower in group 36C than in group 6C and 20C (0.19, 0.68, 0.87 ml/min respectively). Significant elevation of filtration fraction in group 36C suggested that the decrease in GFR mainly resulted from low RPF. Even in group 36C, no glomerular sclerosis was histologically demonstrated in the remnant kidney, and the mean planar area of the remnant glomeruli was significantly small, which might reflect low RPF. Tubulo-interstitial changes like dilatation of the urinary space and tubular epithelial flattening were prominent in group 36C. Beneficial effect of AST-120 was obvious in high protein diet groups. GFR and RPF were rather well preserved in group 36A (0.36 and 0.78 ml/min) with normal filtration fraction. Tubulo-interstitial damage was evidently mild in group 36A. These data suggested the presence of some humoral factors, which can be adsorbed by AST-120 in gastrointestinal tract, and responsible for the deterioration of renal function and tubulo-interstitial damage induced by high protein diet in the uremic condition. Besides hyperfiltration and glomerular hypertrophy, such humoral factors as suggested in this study may contribute to the progression of chronic renal failure to some extent. PMID- 1630030 TI - [The investigation about age-related changes in vasoactive substances of normal subjects and of patients with essential hypertension]. AB - To prove the effect of aging on the synthesis of renin-angiotensin-aldosterone system, renal kallikrein-kinin system, prostaglandin (PG), and thromboxane (TX) which regulate blood pressure, normotensive subjects and patients with essential hypertension (EH) were investigated in the present study. Although plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were decreased with aging in both groups, there is no significant differences between each groups while compared among each age-groups. Urinary excretion of kallikreins (active, inactive and total) in EH were decreased with aging as similar extent to that of normal subjects. There was no age-related change of kallikrein activation ratio in EH in contrary to normal subjects. In comparison with each age-group, the amount of urinary kallikrein excretion in EH were already small in young age groups. The amount of urinary PGE2 excretion in female EH group was smaller than that of normal subjects, and there were no age-related changes in both groups. Urinary excretion of TXB2 and 11-dehydro-TXB2, which are the urinary major metabolites of TXA2 which has potent vasoconstrictive action, were increased in the age-group of 80-93 year-old both normal subjects and EH. There were no age related change in both groups. Although these hypertensive vasoactive substances as renin, aldosterone and TXA2 in EH show the same profile as that in normal subjects, the synthesis of renal antihypertensive vasoactive substances as kallikrein and PGE2 in EH already decrease in younger patients. These results suggest that the lower activities of renal antihypertensive system is a cause of the development of hypertension. PMID- 1630031 TI - [Effect of exercise on rats with renal injury]. AB - Effect of exercise on rats with renal injury was studied. Nephritis was induced in rats by injection of anti-GBM antibody followed by ligation of a branch of the left renal artery after nephrectomy of the right kidney. Moderate daily treadmill exercise was forced on these experimental rats for ten weeks. Sedentary nephritic rats that received the same treatment described above served as controls. The sedentary nephritic rats suffered progressively increasing proteinuria during the time course of the experiment, whereas the nephritic rats with daily treadmill exercise experienced less proteinuria. Mild proteinuria was induced by daily treadmill exercise forced on non-nephritic rats that had received only nephrectomy of the right kidney, but no NTS injection. Light microscopy and immunofluorescence microscopy revealed severe glomerular injury in the sedentary nephritic rats, however, less glomerular injury was seen in nephritic rats with treadmill exercise. Serum cholesterol level was higher in the sedentary rats than in the rats with daily treadmill exercise. The results suggest that daily exercise by nephritic rats will not aggravate renal injury. PMID- 1630032 TI - [Clinicopathological study of membranous glomerulonephritis in patients with rheumatoid arthritis]. AB - Of 103 patients with membranous glomerulonephritis proved by renal biopsy, 11 (10.7%) had rheumatoid arthritis. Nine of these 11 patients received systemic treatment with anti-rheumatic remedies including gold, D-penicillamine and bucillamine. Two others were administered only token of nonsteroidal antiinflammatory drugs. Renal function of the patients was well maintained and within normal limits. Four patients showed nephrotic syndrome, while mild to moderate proteinuria was found in the other 7. Hematuria was minimal to mild, and it was not a major symptom. Six patients resolved proteinuria completely and 2 patients incompletely after discontinuation of chrysotherapy. Nine cases of the membranous lesion in patients with rheumatoid arthritis were stage 1. Thus it was often difficult to identify the glomerular change only by light microscopy. IgA nephropathy and AA amyloidosis were associated in one patient respectively. Our data lead us to conclude that chrysotherapy would cause membranous lesions, but rheumatoid arthritis itself also induce membranous glomerulonephritis. PMID- 1630033 TI - [A case of familial lecithin: cholesterol acyltransferase deficiency]. AB - Lecithin: cholesterol acyltransferase (LCAT) is an enzyme that catalyzes the esterifying reaction of cholesterol in plasma high density lipoprotein (HDL). Deficiency of LCAT is a rare hereditary disease characterized by several clinical symptoms such as proteinuria, corneal opacity, and anemia due to a shortened life span of erythrocytes. In this communication, we report a case of 40 year-old female patient of LCAT deficiency. She visited a hospital for work-up of proteinuria, corneal opacity and anemia. Activity of her serum LCAT was found to be extremely low, and characteristic changes in plasma lipids due to deficiency of LCAT was observed: those were marked decreases in HDL-cholesterol, degree of esterification in serum cholesterol, and apoprotein A-I, A-II, B and C-II levels. The diagnosis of LCAT deficiency was finally made. We studied about histopathological changes in the patient's kidney, and erythrocyte membrane lipid composition and fluidity. Histopathological findings in renal biopsy were follows: a) Light microscopy showed spherical deposits stained with periodic acid Schiff in mesangial matrix and adjacent capillary loops, and hyaline deposits in arterioles, b) Electron microscopy showed vacuoles in mesangial matrix and along the glomerular basement membranes. In erythrocyte membrane lipids, increase of cholesterol to phospholipid molar ratio was evident, being accompanied by changes in phospholipid fractions: increase of phosphatidylcholine, and decreases of phosphatidylethanolamine, sphingomyelin and lysophosphatidylcholine. In phospholipid acyl chains, increase of C18:2 and decreased of C18:1 were evident in the patient. Erythrocyte membrane fluidity was found to be decreased in the patient in a measurement by pyrene, probably being related to the changes in membrane lipid composition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630034 TI - [Acute renal failure due to rhabdomyolysis--clinical investigation on our 6 cases]. AB - Six cases of acute renal failure (ARF) due to rhabdomyolysis were experienced between 1984 and 1989. Patients' ages ranged from 33 to 92 years old (average ages 61) and all were male. The causes of rhabdomyolysis were as follows: one crush syndrome, one acute arterial occlusion, one diabetic hyperosmolar nonketotic coma and three cases of malignant syndrome due to neuroleptica (mainly haloperidol). Underlying diseases included, one case of abdominal aneurysm, two cases of diabetes mellitus, two cases of schizophrenia and one case of reactive psychosis. Dehydration was considered as an important factor in the onset of rhabdomyolysis and ARF, because it was observed in 4 of the cases in this study. In all cases, the serum levels of potassium, phosphorus and uric acid as well as myoglobin and myogenic enzymes increased markedly. In patients with myoglobinuric ARF, severe metabolic acidosis and hypocalcemia in the oliguric phase and hypercalcemia in the diuretic phase were prominent. Muscle biopsy showed myolytic degeneration in 2 of 4 cases. Five cases were treated with hemodialysis and one case was managed conservatively. All 6 cases had relatively good prognosis. However, 3 cases with malignant syndrome showed outcomes more severe than in the other 3 cases without such syndrome. PMID- 1630035 TI - [A case of MCTD patient with recurrent hemoperitoneum receiving CAPD who had a successful recovery with an increase in steroids]. AB - A-48-year-old man with end stage renal disease due to MCTD started CAPD in February 1988. He also had been treated by steroid therapy which was gradually decreased. He had seven hemoperitoneum episodes for ten months and two years since starting CARD. None of episodes were associated with CAPD catheter nor bacillus peritonitis. While he had had long term hemoperitoneum episode in March 1989, he was received no steroid and had leucopenia and low compliments. Therefore he was treated by steroids again. He had no hemoperitoneum episodes for seventeen months since re-steroid therapy. And he recovered from leucopenia and low compliments. It seems that the mechanisms of hemoperitoneum are due to immunological abnormality associated with MCTD. PMID- 1630036 TI - [Basic understanding of retroviruses]. AB - Retroviruses contain a reverse transcriptase in the virion that converts viral genomic RNA to proviral DNA. Retroviruses are divided into three groups; oncovirus, lentivirus, and spumavirus. The oncovirus group contains HTLV-1, which causes adult T-cell leukemia, encephalomyeloneuropathy, arthritis, and alveolo bronchopathy. The lentivirus groups contains HIV, which causes acquired immunodeficiency syndrome and dementia. The genomic structures and functions of HTLV-1 and HIV have been demonstrated to explain the pathogenesis of these retroviruses. PMID- 1630037 TI - [Pulmonary lesions of acquired immunodeficiency syndrome--analysis of 24 Japanese autopsy cases with AIDS]. AB - The pulmonary lesions were studied in 24 autopsy cases of Japanese patients with AIDS. The major pathological findings were opportunistic infections, which were the major clinical symptoms in some patients. The pathogens identified were as follows; Pneumocystis carinii (PC) in 10, cytomegalovirus (CMV) in 14, atypical mycobacterium in 5, cryptococcus in 2, candida in 2, and nocardia in 1. PC pneumonia was prominent in 8 cases and was the cause of death. In such patients, the lung were heavy and appeared parenchymatous. Histological examination revealed numerous protozoa in the foamy material in the alveolar spaces, associated with swelling of the alveolar lining cells and edematous thickening of the alveolar septa. In some cases, only hyaline membrane formation was prominent without foamy material in the alveolar spaces. Immunostaining with anti-PC monoclonal antibody or in-situ hybridization with oligopeptide demonstrated pathogens in the hyaline membranes. Many cases with PC pneumonia had concomitant opportunistic infections such as CMV, Herpes simplex virus, and atypical mycobacterium. Extrapulmonary infection of PC was seen in only one case. CMV infection was found in 14 cases; 7 had innumerable inclusion bodies, and in some cases the lesions were most prominent around the bronchioles. Of the 5 cases of atypical mycobacterial infection, 2 were caused by M. kansaii (MK) and 3 by M. avium intracellulare (MAI). Both lesions of MK infection showed necrosis and cavitation. One of three cases of MAI infection showed cavitation. Around the cavitary lesions, numerous cytomegalic inclusion bodies were identified in the mesenchymal cells, which may have been the cause of necrosis and cavitation of the lesions. MAI infection was systemic and pronounced in the lymph nodes, spleen, and intestinal mucosa. Neoplastic lesions comprised 2 cases of Kaposi's sarcoma and 4 of extranodal non-Hodgkin lymphoma in other organs. Lung involvement was seen in only one case of Kaposi's sarcoma although very small in size. The lesion was situated along the pulmonary vein and appeared hemorrhagic macroscopically. Pulmonary lesions in AIDS are complicated, and many of opportunistic pathogens were identified in single patients. PMID- 1630038 TI - [Epidemiology of HTLV-I carriers in Hirado Island and virological and immunological investigation of HTLV-I associated pulmonary disease]. AB - Adult T-cell leukemia (ATL) is endemic in Kyushu. Our study at Hirado island in Nagasaki prefecture revealed a higher incidence (35.9%) of HTLV-I carriers in villages with fishing than in those without (16.5%). HTLV-I carriers showed a higher incidence of abnormal findings on chest roentgenogram (21.7%) than non carriers (16.5%), but most were lesions of old pulmonary tuberculosis and pleural thickening. Virological and immunological investigations were performed for 10 HTLV-I carriers, 3 patients with HTLV-I associated myelopathy (HAM), and 3 patients with ATL to determine the presence of HTLV-I associated pulmonary disease. In HAM patients, there were high titers of anti HTLV-I antibody, positive IgA reaction to HTLV-I, and an increase in interleukin-2 receptor (IL-2) positive T-cells in the peripheral blood; and lymphocytosis and an increase in IL 2-positive T-cells in the bronchoalveolar lavage fluid (BALF). Virological examination showed the presence of pX gene and tax1/rex1 mRNA in the peripheral blood and BALF. Similar immunological and virological findings in 2 of 10 carriers suggested the presence of HTLV-I associated pulmonary disease. PMID- 1630039 TI - [Natural history of HTLV-I infection]. AB - Adult T-cell leukemia (ATL), a disease entity first described by Takatsuki et al., is endemic in southwestern Japan, the Caribbean Islands, and in some parts of Africa. ATL patients are classified into four subtypes according to the clinical picture: acute, chronic, smoldering, and lymphoma type. The diagnosis of ATL is made from the characteristic clinical findings, the detection of serum antibodies to HTLV-I, and when necessary, the confirmation of monoclonal integration of HTLV-I proviral DNA in cellular DNA of ATL cells. Recently, diagnostic criteria for clinical subtypes of ATL were proposed by the Lymphoma Study Group in Japan: 1) smoldering type, normal lymphocyte level, no hypercalcemia, lactate dehydrogenase (LDH) value 1.5 times the upper limit of normal or lower, no lymphadenopathy, no involvement of liver, spleen, central nervous system (CNS), bone or gastrointestinal tract, and no ascites or pleural effusion: 2) chronic type, absolute lymphocytosis with T-lymphocytosis of greater than 3 x 10(9)/1, LDH value twice the upper limit of normal or lower, no hypercalcemia, no involvement of CNS, bone, or gastrointestinal tract, and no ascites or pleural effusion: 3) lymphoma type, no lymphocytosis, 1% or less abnormal lymphocytes, and histologically-proven lymphadenopathy: 4) acute type, remaining ATL patients who are not classified as any of the above types. Infection with HTLV-I is a direct cause of ATL. Furthermore, infection with this virus can indirectly cause many other diseases via the induction of immunodeficiency, such as chronic lung diseases, opportunistic lung infections, cancer of other organs, monoclonal gammopathy, chronic renal failure, strongyloidiasis, non-specific dermatomycosis, non-specific lymph node swelling, HTLV-I associated myelopathy (HAM/TSP), and HTLV-I uveitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630040 TI - [Bronchopneumonopathy in HTLV-1 associated myelopathy (HAM) and non-HAM HTLV-1 carriers]. AB - Human T-cell leukemia virus type 1 (HTLV-1) causes not only adult T-cell leukemia (ATL), but also HTLV-1 associated myelopathy, a recently described slowly progressive spastic paraparesis, in its carrier state. Pulmonary involvement has been reported in HAM patients. Based on bronchoalveolar lavage or histological examination, the pulmonary involvement has been characterized by accumulation of T-cells, especially activated T-cells, in the lung. We reviewed our data on pulmonary involvement in HAM, which suggested that the characteristic pulmonary involvement observed in HAM was not restricted to HAM patients, but was also observed in non-HAM HTLV-1 carriers. Based on the data, we report that HAM is a systemic disease and that HTLV-1 causes characteristic pulmonary involvement, which we termed HTLV-1 associated bronchopneumonopathy (HAB). PMID- 1630041 TI - [Pathogenesis of T-lymphocyte alveolitis associated with HTLV-I infection]. AB - Pulmonary involvement has been demonstrated in patients with spastic myelopathy associated with HTLV-I infection (HAM/TSP). Pulmonary lesions in these patients are characterized by T-lymphocytosis and increased level of soluble IL-2 receptor in bronchoalveolar lavage fluid. T-lymphocytes from peripheral blood and bronchoalveolar lavage fluid proliferated spontaneously and released IL-2 and IL 2 receptor when cultured in vitro. Spontaneous proliferation of T-lymphocytes was also found in HTLV-I carriers without myelopathy, but less intensely than in HAM/TSP patients. Interestingly, HTLV-I-infected cells were markedly increased in bronchoalveolar lavage fluid from HAM/TSP patients compared to HTLV-I carriers without myelopathy. These results suggest that T-lymphocyte activation and increased HTLV-I-infected cells play an important role in the pathogenesis of pulmonary involvement in patients with HAM/TSP. PMID- 1630042 TI - [HABA (HTLV-I associated bronchiolo-alveolar disorder)]. AB - The presence of antibodies to adult T cell leukemia (ATL) antigen: HTVL-I was studied in patients with chronic interstitial lung diseases such as diffuse panbronchiolitis (DPB) and idiopathic interstitial pneumonia (IIP). Anti-HTLV-I antibody was detected with a high frequency among these diseases (35% in DPB and 7% in IIP) compared with other diseases and healthy controls. We have termed the clinicopathological condition that includes these two disease categories of interstitial lung disease (DPB or IIP) and hematologic disorder (ATL associated with HTLV-I carrier state) HTLV-I associated bronchiolo-alveolar disorder (HABA). At the same time, HTLV-I related reaction (diffuse pattern for MT-1 and/or MT-2) was found except positive reaction of the antibody (granular pattern for MT-1) by immunofluorescent assay. The incidence of HTLV-I related reaction was high in interstitial lung diseases with a rate of 45% in DPB and 53% in IIP. Thus, the total frequency of presence of antibodies and related reactions was 80% in DPB and 60% in IIP. In lung cancer, the frequency was also high, although it was less than in DPB and IIP. We termed cases of anti-HTLV-I antibody positive lung cancer HTLV-I associated lung cancer (HALC). One typical patient with IIP who initially showed HTLV-I related reaction showed a positive antibody reaction 2 years later. Finally he presented with adenocarcinoma with effusion a further 2 years later. In order to examine HTLV-I proviral DNA integration, southern blotting by PCR was performed in patients with HTLV-I related reaction.2+ suggesting one of the causes of DPB. PMID- 1630043 TI - [Evaluation of plasma SC5b-9 (SMAC) in patients with ARDS]. AB - The adult respiratory distress syndrome (ARDS) occurs in patients with various underlying illnesses. It has been suggested that complement activation may play a crucial role in the pathophysiology of ARDS by direct actions of complement fragments and/or by release of mediators including endotoxin, superoxide anion, and arachidonate metabolites. Therefore, complement evaluation was performed in patients with ARDS, with emphasis on SC5b-9 (Membrane Attack Complex). Complement split products, C4d, Bb, and SC5b-9, respectively from the classical, alternative, and terminal complement pathway were measured by enzyme immunoassay (EIA) using respective monoclonal antibodies. Plasma S-protein (vitronectin) concentration was also evaluated by EIA. We could not detect SMAC in normal controls or in a C5-deficient patient with abdominal infection. In contrast, most patients with ARDS and patients at risk showed elevated SMAC, and an increase in the values in association with exacerbation of the disease. However, two patients with ARDS exhibited lower values of SMAC in spite of deterioration and subsequent death. It was suggested that in these two ARDS patients, liver dysfunction may have contributed to the reduced SMAC formation. The finding that S-protein concentration (a MAC inhibitor) in the plasma of these two patients was reduced supports this speculation. It is suggested that simultaneous evaluation of SMAC and S-protein in plasma is helpful in determining the prognosis of critically ill patients. PMID- 1630044 TI - [Use of beta-agonist inhalation concomitantly with regular beclomethasone dipropionate in patients with bronchial asthma--as required or on a regular basis]. AB - We investigated whether regular use of beta-agonist inhalation concomitantly with regular beclomethasone dipropionate (BDP) inhalation is necessary in chronic bronchial asthma. Twenty chronic asthmatic patients who were stable on regular BDP and beta-agonist inhalation were studied. After a 2 week observation period, the patients were randomly assigned to two groups. One group received BDP 400 micrograms/day (2 puffs 4 times) and beta-agonist inhalation as required for 4 weeks. This period was followed by 4 weeks of treatment with BDP 400 micrograms/day and regular beta-agonist inhalation. The other group received these treatments in the reverse order. No significant differences among the two groups were observed in attack score, ADL score, sleep score, and %PEFR. In addition, no differences were detected in these parameters between the periods of regular use of beta-agonist and the periods of use as required. The frequency of inhalation of beta-agonist during the use as required period correlated with the sleep score and difference in %PEFR between morning and night, and was significantly lower than the frequency of inhalation during the period of regular. From these results, we conclude that inhalation of beta-agonist on a regular basis is not necessary to achieve the same degree of relief of symptoms as treatment with beta 2-agonist and BDP inhalation on regular basis in patients with chronic asthma. PMID- 1630045 TI - [Distribution of ferruginous bodies in the lung in cases of malignant pleural mesothelioma with definite occupational history of asbestos exposure]. AB - The distribution of ferruginous bodies in the lung in cases of malignant pleural mesothelioma with definite occupational history of asbestos exposure was examined, and the length of ferruginous bodies and the kinds of asbestos fibers were also evaluated. Ferruginous bodies were most numerous in the upper lobes, especially in S1, and were least numerous in the lower lobes. On the other hand, the longest ferruginous bodies were detected in the lower lobes. Amosite and crocidolite (amphibole groups) were found in almost all cases of malignant pleural mesothelioma, but chrysotile was found in only one case. The longer fiber length of asbestos in the amphibole group was considered to be important in the carcinogenicity of malignant mesothelioma, since almost all cases of malignant mesothelioma originated from the lower pleura. PMID- 1630046 TI - [Airway and alveolar inflammation assessments with bronchoalveolar lavage in various interstitial lung disorders]. AB - Fractional analysis of bronchoalveolar lavage (FABAL) fluid was performed in 6 control patients and 41 patients with various interstitial lung disease. The cell differential counts in the first 30 ml fraction of BAL (FBAL-I), which is considered to be the bronchial lavage, differed from those of the 50 ml second and third fraction (FBAL-III). Hypersensitivity pneumonitis, pulmonary tuberculosis, and sarcoidosis showed a high recovery of lymphocytes (52%); however, the former two disorders were occasionally, associated with neutrophil airway inflammation, whereas sarcoidosis was not. The percentage recovery of neutrophils in total FBAL was considerably high in patients with diffuse panbronchiolitis, and relatively high in those with collagen vascular disease, idiopathic pulmonary fibrosis, pneumoconiosis, and control smokers. However, these neutrophils were largely recovered from FBAL-I, suggesting the presence of airway inflammation. Thus, it is valuable to apply the FBAL method to determine the topographic distribution of inflammatory cells in the lungs. It was also found that the lymphocyte morphology in the lavage fluid was of value in establishing the diagnosis of hypersensitivity pneumonitis, and it is critical whether or not mast cells and basophils are present in BALF since they indicate the pathologic state of allergy or fibrosis. Although present in various fibrotic lung diseases in a limit number, langerhans cells are a diagnostic marker for histiocytosis X. PMID- 1630047 TI - [The candida antigen titer by CAND-TEC in patients with pulmonary disease]. AB - In order to elucidate the background of candida infection in patients with pulmonary disease, we divided 100 patients into 2 groups according to their serum titer of CAND-TEC determined by latex agglutination test for candida antigen. Group C1 (83 patients) had CAND-TEC value less than 2:1, and Group C2 (17 patients) had CAND-TEC value greater than 4:1. There was a significantly higher incidence of respiratory failure, hypoalbuminemia, and fever unresponsive to antibiotics in Group C2 compared with Group C1. Regarding the sputum culture of candida, there were significantly more positive cases in Group C2 than in Group C1. Furthermore, Group C2 showed a significantly poorer prognosis than Group C1. Generally, the candida antigen titer correlated well with clinical findings and with the course of infection and treatment with antifungal drugs. These results suggest that administration of antifungal drugs may be indicated in patients with fever unresponsive to antibiotics when the candida antigen titer is greater than 4:1. PMID- 1630048 TI - [The appearance of "central core of respiratory muscle" in patients with respiratory failure]. AB - We report the histological and histochemical features of core fibers present in respiratory muscles obtained from autopsy since 1980. Fifty autopsy cases of adults without neuromuscular disease were examined. "Central core" structure was present in 38 cases and absent in 12 cases. The duration of D.O.E. was greater than 1 month in 81.8% of core positive cases. In core negative cases, the duration of D.O.E. was less than 3 months. "Central core" structure were present in 80.0% of chronic respiratory failure cases and 41.7% of non-chronic cases. It is suggested that central core in respiratory muscles develops less than 3 months after the onset of D.O.E. PMID- 1630049 TI - [The relation between bronchial infiltration of eosinophils and bronchial hyperresponsiveness in two cases of eosinophilic pneumonia]. AB - We evaluated the bronchial hyperresponsiveness to methacholine in the two cases of eosinophilic pneumonia with infiltration of eosinophils into bronchial mucosa. Bronchial responsiveness was not increased in either case in spite of marked infiltration of eosinophils into the bronchial mucosa and submucosa. Hypodense eosinophils are reported in the sputum of patients with bronchial asthma. This suggests that infiltration of activated eosinophils into the bronchial mucosa is an essential factor in bronchial hyperresponsiveness. PMID- 1630050 TI - [Changes in pulmonary epithelial permeability due to thoracic irradiation]. AB - The changes in pulmonary epithelial permeability during and following radiation therapy were studied in 10 patients with malignant diseases of the chest; 9 patients with bronchogenic carcinoma and one with thymoma. 99mTc-DTPA aerosol was inhaled during tidal breathing with the patient in supine position, and radioactivity was measured anteriorly by a gamma camera and recorded on a computer. Half time clearance (t1/2) was calculated from exponential fitting of time activity curves by regression analysis in various regions of interest in the initial 7 min following completion of aerosol inhalation. Studies were made every two weeks. In patients who developed radiation pneumonitis, t1/2 values decreased and reached the nadir at the time of manifest pneumonitis, indicating increased pulmonary epithelial permeability. Increased pulmonary epithelial permeability was observed not only in the pneumonic regions but also in the contralateral normal lung regions. Steroid therapy reversed these changes. Increased pulmonary epithelial permeability was observed in 2 out of 5 patients who did not develop radiation pneumonitis. In summary, pulmonary epithelial permeability changes occur not only in regions of radiation pneumonitis but also in non-irradiated lung regions following radiation therapy. We consider that the judicious use of this method enables detection of changes in pulmonary epithelial permeability prior to the development of clinical manifestations of radiation pneumonitis. PMID- 1630051 TI - [A case of occupational asthma caused by arrowhead scale in mandarin orange worker]. AB - A 50-year-old woman with occupational asthma, whose attacks were provoked by inhalation of Arrowhead scale (Unapsis Yanonensis Kuwana) attached to the leaves of mandarin oranges is reported. She experienced asthmatic attacks while picking leaves and harvesting mandarin oranges. Because Arrowhead scale-dust stuck to the leaves was suspected to be the allergen, tests of allergy were performed using an extract of the allergen prepared by Unger's method in our laboratory. Asthmatic attack was provoked 90 minutes after inhalation of the extract of cocoon. Histamine was not released, but leukotriene D4 production was induced by the addition of the extract to whole blood. Basophils were activated by addition of anti-IgG anti-sera as well as the extract. These data indicate that LT released from target cells in response to the worm elements, as well as histamine, is important as a chemical mediator. PMID- 1630052 TI - [Inhibitory effects of alpha 1 protease inhibitor on the production of IL-1 and TNF alpha by alveolar macrophages in patients with lung cancer]. AB - In the present study, we investigated the effect of alpha 1 protease inhibitor (alpha 1PI) on the production of interleukin-1 alpha (IL-1 alpha, ELISA), IL-1 beta (ELISA), and tumor necrosis factor alpha (TNF alpha, ELISA) by alveolar macrophages (AM) recruited by bronchoalveolar lavage (BAL) from patients with lung cancer and benign pulmonary diseases. Levels of BALF alpha 1PI were significantly increased in patients with lung cancer compared with benign pulmonary diseases. When BALF AM were cultured and stimulated by LPS (20 micrograms/ml) for 48 hours, production of IL-1 alpha and IL-1 beta was less marked in patients with lung production showed a similar tendency, but the difference between patients with lung cancer and benign pulmonary diseases was not significant. Addition of alpha 1PI to the LPS-stimulated AM culture system inhibited production of these cytokines dose-dependently. Thus, the local increase of alpha 1PI in lung cancer may act as a humoral inhibitor against the production of IL-1 and TNF by AM. PMID- 1630053 TI - [Study of the duration of antimicrobial chemotherapy in mycoplasmal pneumonia]. AB - We assessed the period of administration of antibiotics required for cases of mycoplasmal pneumonia. The subjects were 38 patients with mycoplasmal pneumonia admitted to our hospital. These patients were treated with 100 mg minocycline or 500 mg erythromycin by intravenous infusion twice a day. They were divided into a 6 day-administration group (Group A; 16 cases) and a 9 day-administration group (Group B; 17 cases). Administration was discontinued on the 4th day or earlier in 5 cases due to side effects. A comparative assessment was made between Groups A and B with respect to body temperature, WBC, erythrocyte sedimentation rate, CRP, and chest X-ray on the 3rd, 6th, and 9th days of treatment, but no significant difference was observed. Residual shadows at the end of treatment were present in 100% of Group A and in 47% of Group B, but they disappeared gradually in both groups. No cases of recurrence were observed in either Group A or B within 1 month after the completion of treatment. Regarding the treatment period for mycoplasmal pneumonia by intravenous infusion of minocycline or erythromycin, no significant clinical difference was observed between the 6 day-administration group and the 9 day-administration group, suggesting that 6 days of administration is sufficient for treatment. PMID- 1630054 TI - [Clinical study of respiratory infection due to Branhamella catarrhalis using transtracheal aspiration]. AB - We clinically investigated 40 cases of respiratory infection due to B. catarrhalis by transtracheal aspiration (TTA). The cases consisted of acute bronchitis (13 cases), pneumonia (14 cases), and chronic lower respiratory tract infection (13 cases). The infection was monomicrobial in 17 cases and polymicrobial in 23 cases with respect to the organisms isolated from TTA. The principal organisms isolated in combination with B. catarrhalis in cases of polymicrobial infection were S. pneumoniae and H. influenzae. All of the 6 cases of death were patients with pneumonia who had malnutrition and immunological hypofunction. These results suggest that B. catarrhalis is an important pathogen in respiratory infection. PMID- 1630055 TI - [Lymphangiomyomatosis with a large retroperitoneal tumor]. AB - A case of lymphangiomyomatosis (LAM) in a 35-year-old woman is reported. Because she was already severely dyspneic when she was admitted to our hospital, neither TBLB nor open lung biopsy was performed, and no accurate diagnosis was made. She died of respiratory failure three years after the development of exertional dyspnea, and autopsy revealed LAM. Pneumothorax, a well-known and frequent complication of LAM, did not occur until one month prior to her death. Although pneumothorax frequently complicates LAM, there are a few reports of cases in which pneumothorax did not occur during the course of the disease. We emphasize that LAM should be considered in the differential diagnosis of diffuse interstitial lung disease, even when the patient has no pneumothorax. The retroperitoneal tumor (15 x 10 x 10 cm), which was evident clinically, was later shown to be intra-abdominal involvement of LAM. Although only a few cases of LAM with a large retroperitoneal tumor have been reported, minor intra-abdominal involvement is relatively common. This case also suggested that the finding of a retroperitoneal tumor may be a diagnostic clue in LAM. PMID- 1630056 TI - [A case of alveolar hydatid disease of the lung in the Kansai district of Japan]. AB - A 78-year-old man was admitted to hospital because of episodes of high grade fever and multiple nodular shadows on chest roentgenogram. He had a past history of percutaneous drainage and partial resection of the left lobe of the liver for liver abscess of unknown origin in 1987. The high grade fever was secondary to sepsis due to Citrobacter freundii. The sepsis improved with antibiotic therapy, but the abnormal shadows on chest roentgenogram did not improved. Immunoserological tests indicated a probable diagnosis of alveolar hydatid disease of the lung, which is very rare in the Kansai district of Japan. Open lung biopsy was performed and the diagnosis of alveolar hydatid disease of the lung was confirmed. PMID- 1630057 TI - [A case of occult breast carcinoma with micronodular shadows on chest x-ray film]. AB - A 57-year-old woman was admitted to our hospital for the evaluation of roentgenological micronodular shadows of the bilateral middle and lower lung fields. Physical findings were normal except for left axillary lymph adenopathy. The level of tumor marker NCC-ST-439 was markedly elevated (2800 U/ml). Histological examination of the transbronchial biopsy and the swollen lymph node biopsy specimens showed proliferation of identical tumor cells. Breast or lung carcinoma was suspected as the primary site. Echogram of the left breast showed microcalcification without a mass. The biopsy specimen obtained from the calcified lesion indicated occult breast carcinoma. From these findings the diffuse micronodular shadows on the chest roentgenogram were considered to be the metastatic lesions of occult breast carcinoma. This case indicates that occult breast carcinoma should be considered as a possible primary site for diffuse pulmonary metastatic lesions. PMID- 1630058 TI - [A case of Wegener's granulomatosis with a giant solitary pulmonary mass]. AB - A 44-year-old woman was admitted to hospital with a history of high fever, cough, and weight loss. Her chest X-ray film showed a giant solitary pulmonary mass in the left lower lobe. After admission, she developed bilateral eyeache and left exophthalmos. CT film of the head showed a massive lesion in the sinuses. Biopsy specimens obtained from both massive lesions showed either epithelioid granulomas with Langhans' giant cells or necrotising vasculitis. Antineutrophil cytoplasmic antibodies, which have high sensitivity and specificity for active WG, were found. The diagnosis of WG was thus made. PMID- 1630059 TI - [A case of bronchiolitis obliterans organizing pneumonia with positive anti Jo-1 antibody preceding polymyositis]. AB - We describe a 58-year-old female with BOOP associated with polymyositis. Four months prior to the appearance of distinctive manifestation of polymyositis, she presented with a two-week history of cough, dyspnea on exertion, and fever. Chest roentgenogram demonstrated bilateral basal infiltrative shadows. The patient was treated with prednisolone, 30 mg/day because of progressive hypoxemia. Open lung biopsy revealed organizing masses of granulation tissue extending from the respiratory bronchioles into the intra-alveolar spaces, which was consistent with BOOP. She developed muscle pain in her legs, fever, dry cough, hypoxemia, and high CPK value in the course of tapering of steroid dose. The findings of biopsy from the left rectus femoris muscle were compatible with polymyositis. Retrospective study of the patient's serum on admission showed positive anti Jo-1 antibody. PMID- 1630060 TI - [A case of recurrent pulmonary alveolar proteinosis treated by pulmonary lavage: were the remissions due to the natural course or due to the lavage?]. AB - We report a 39-year-old male with pulmonary alveolar proteinosis. Although no abnormal shadows were seen on regular check-up chest roentgenogram one year previously, diffuse alveolar filling shadows were noted on admission, suggesting fairly acute progression of the disease. He was treated with bronchoalveolar lavage of each segment of both lungs by flexible fiberoptic bronchoscope under local anesthesia. Following this treatment, the shadows on X-ray film and shortness of breath resolved. Oxygen tension of arterial blood, pulmonary function, and serum CEA recovered to almost within normal ranges. The shadows deteriorated twice, but therapeutic lavage performed at the outpatient clinic was effective on each occasion. He thus received 3 series of bronchoalveolar lavage over a period of more than 3 years. We followed the clinical course of this patient for 6 years, and he remained well 3 years after the final treatment. PMID- 1630061 TI - [A case of loxoprofen-induced pulmonary eosinophilia]. AB - A 65-year-old female suffering from lumbago, headache, and hypertension had been treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and antihypertensive drugs. On June 13, 1990, 2 weeks after the commencement of loxoprofen administration, she developed cough and low grade fever. She was treated with antibiotics and NSAIDs without improvement. Laboratory data showed marked eosinophilia (2200/mm3), elevation of IgE (3090 IU/ml), and liver dysfunction. Her chest X-ray revealed no active lesion, but the percentage of eosinophils in BALF was elevated (38%). Because drug-induced eosinophilic pneumonia was suspected, all drugs were discontinued. Her symptoms improved and the abnormalities of laboratory data normalized. The lymphocyte stimulation test was weakly positive with three NSAIDs (loxoprofen, pranoprofen, and alminoprofen). The challenge test by loxoprofen reproduced eosinophilia and liver dysfunction, suggesting that she had loxoprofen-induced eosinophilic pneumonia. To our knowledge, this is the first reported case of loxoprofen-induced lung injury. PMID- 1630062 TI - [A case of vocal cord dysfunction diagnosed as bronchial asthma, that was improved by psychosomatic therapy]. AB - A 19-year-old psychologically disturbed female was admitted to our hospital because of intractable dyspnea and wheezing for twenty two months. She had been diagnosed as having asthma and had received several medications including steroids before admission to our hospital. According to our clinical observations, she was considered not to have asthma because neither FEV1.0 nor PaO2 was decreased during the periods of wheezing and FEV1.0 was not changed by inhalation of bronchodilators, although she had a family history of allergy and false bronchial hyperreactivity by asthograph. On physical examination, diffuse wheezing was heard mainly over the larynx during inspiration at the times of dyspnea. There was flattening of the inspiratory flow-volume loop during wheezing. Bronchoscopy performed during an attack confirmed that wheezing was due to adduction of the vocal cords throughout the respiratory cycle. Therefore, this case was diagnosed as vocal cord dysfunction. Her symptom was considered to be a form of conversion reaction derived from her unhappy past history. Following psychosomatic therapy, all of her medications became unnecessary. She understood the mind-body relationship of her condition, and learned to achieve self-control. PMID- 1630063 TI - [A case of re-expansion pulmonary edema following water seal drainage for spontaneous pneumothorax--management with right and left-separated mechanical ventilation]. AB - A 23-year-old male with complete collapse of the right lung due to spontaneous pneumothorax was admitted 11 days after its onset. Paying close attention to the re-expansion pulmonary edema (REPE), water seal drainage was performed. Following couple episodes of persistent severe cough, four hours later, he developed dyspnea and began to expectorate frothy massive sputum. Chest X-ray revealed pulmonary edema of the entire right lung field. Measurement of total proteins and neutrophil elastase in airway exudates showed 5.5 g/dl (ratio to plasma, 0.89) and 7000 micrograms/l, respectively. Because of marked difference of compliance between bilateral lungs, management with right and left-separated mechanical ventilation and PEEP applied only to the right lung was performed. Although transient mediastinal deviation to the left was observed, successful management was achieved by the maneuver. High concentrations of total proteins and neutrophil elastase in edema fluid suggest that increased vascular permeability due to endothelial cell injury via activated neutrophils is mainly responsible for REPE. In the present case, rapid expansion of the collapsed lung accelerated by severe cough seems to be a predisposing factor of REPE. In patient with prolonged pneumothorax, suppression of cough is thought to be important for the prevention of REPE even with water seal drainage. PMID- 1630064 TI - [Alpha 1-antitrypsin deficiency with bronchiectasis in two sisters]. AB - Two sisters with alpha 1-antitrypsin deficiency and bronchiectasis are reported. The 53-year-old older sister (propositus) had pneumonia 3 times during her forties. She developed dyspnea on exertion in February, 1988, and a few months later she was seen at our hospital. Her serum alpha 1-antitrypsin level was 11 mg/dl. Vascular markings on chest X-ray were mildly decreased. Bronchography showed generalized cystic bronchiectasis. The younger sister was seen at our hospital at the age of 50. She had been in good health until one year previously when she had developed pneumonia, and thereafter she had suffered from productive cough and dyspnea on exertion. Her alpha 1-antitrypsin level was 22 mg/dl. Chest X-ray showed ring-like shadows and tram lines. Chest CT scans of both sisters revealed cystic changes, dilatation of bronchi, and the connection of these lesions diffusely. The alpha 1-antitrypsin phenotype of these sisters was found to be PiSiiyama (homozygote). Family study revealed that alpha 1-antitrypsin levels of 7 members were intermediate and no members had symptoms. We consider that bronchiectasis may have been related to alpha 1-antitrypsin deficiency in these sisters. PMID- 1630065 TI - [A case of dimethyl sulfate intoxication manifested by persistent dyspnea]. AB - A 35-year-old man had been exposed to the vapor of dimethyl sulfate which was split over the bed of a truck from an accidentally broken container. After receiving treatment at the critical care unit of our university hospital for respiratory failure, he was transferred to our ward with dyspnea persisting for one month. Chest X-ray showed diffuse nodular and infiltrative shadows and shadows suggestive of bronchial wall thickening. Bronchoscopy demonstrated tracheobronchial stenosis due to severe inflammation, and transbronchial lung biopsy revealed erosion and granulation in tissues of the bronchiolar walls. These findings suggested extensive inflammatory involvement of the respiratory tract extending from the trachea to the bronchioles. Treatment with antibiotics, especially agents with antipseudomonal activity, was effective against secondary pneumonia. Administration of corticosteroid for stenotic lesions of the airway was extremely beneficial. The clinical course of the respiratory lesion caused by dimethyl sulfate intoxication was following, including the bronchoscopic findings. The efficacy of treatment with corticosteroid and antibiotics was evaluated by successive bronchoscopic examinations of the lesions. PMID- 1630066 TI - Common aspects of the cerebral regulation of thirst and renal sodium excretion. AB - It has been shown that several mammalian species increase the excretion of sodium in urine as they become dehydrated. This dehydration-induced natriuresis occurs despite simultaneous hypovolemia, and it can be blocked by an experimentally induced reduction in the sodium concentration of CSF, or by ablation of the periventricular tissue in the vicinity of the lamina terminalis. These two experimental procedures also disrupt thirst and vasopressin secretion. There may therefore be common features involved in the central control of osmoregulatory thirst, vasopressin secretion and sodium excretion. Experimental evidence in sheep suggests that whenever the tonicity of body fluids increases, a centrally mediated natriuretic mechanism is engaged. This cerebral natriuretic mechanism may contribute along with other influences such as the extracellular fluid volume, aldosterone and atrial natriuretic peptide, to determine the rate of sodium excretion by kidneys. The efferent pathway from brain to kidney mediating osmoregulatory natriuresis is not known. It is probably hormonal, because renal denervation does not disrupt such natriuresis. PMID- 1630067 TI - Aging and sodium homeostasis. AB - Deterioration of glomerular filtration rate appears to be progressive throughout life whereas sodium intake tends to remain constant. The influence of aging may be amplified by intrinsic renal disease, unilateral nephrectomy or renovascular abnormalities. Changes in the tubular reabsorption of sodium will allow the excretory capacity of the kidney to adjust to fluctuations in normal sodium intake. However, restriction of dietary sodium may be associated with a sluggish renal response; a sodium wasting state that could lead to significant deterioration in renal function and orthostatic hypotension, may occur. Conversely, increasing dietary sodium in older subjects may result in a rise in arterial pressure more often than in younger subjects. Dietary sodium restriction should be carefully controlled in elderly subjects. PMID- 1630068 TI - Studies on blood pressure regulation in hypertensive ren-2 transgenic rats. AB - Transgenic rats harboring the mouse ren-2 gene develop severe hypertension in association with suppressed kidney and plasma renin levels. Extra-renal expression of the ren-2 gene occurs in a number of sites, and is particularly high in the adrenal cortex. We have investigated the response of blood pressure and heart rate in ren-2 rats to acute converting enzyme inhibition and to sodium depletion. In response to a single dose of captopril (1 mg/kg i.p.), blood pressure in ren-2 rats was rapidly normalized, whereas normotensive Sprague Dawley rats were relatively unresponsive to captopril. In response to the sodium depletion protocol (five days on low-sodium diet, with furosemide administered on day 1) both ren-2 rats and normotensive Sprague-Dawley rats underwent similar initial losses of sodium followed by a gradual return to net sodium balance. Diastolic pressure in ren-2 rats fell from 160 +/- 9 mm Hg to 105 +/- 10 mm Hg after 72 hours, whereas blood pressure in Sprague-Dawley rats was essentially unchanged. The response to captopril implies a major role for angiotensin II in sustaining hypertension, and this may result from tissue generation of angiotensin I. The response to sodium depletion suggests a volume-dependent component, which may result from elevated aldosterone levels, possibly due to enhanced adrenal renin expression. PMID- 1630069 TI - Spectral analysis of short-term blood pressure and heart rate variability in uremic patients. AB - Short-term fluctuations in blood pressure (BP) and heart rate (HR) were quantified to assess autonomic nervous system (ANS) dysfunction in six dialysis patients, compared to six control subjects of similar age. Indirect finger BP was measured by a Finapres device. Analog-to-digital conversion of the BP was used to determine systolic BP (SBP), diastolic BP (DBP) and HR every second. The equidistant sampling allowed a direct spectral analysis using a fast Fourier transform algorithm. Uremic patients exhibited reduced BP and HR short-term variabilities, with a dramatic reduction in the amplitude of the 0.1 Hz component (Mayer waves) of SBP and DBP spectra. Dialysis did not produce any consistent immediate improvement in the amplitude of the Mayer waves. Our study thus indicates impaired cardiovascular ANS function in uremic patients. PMID- 1630070 TI - Arterial pressure control in the sympathectomized rat. PMID- 1630071 TI - Twenty-four hour blood pressure variability: clinical implications. AB - Ambulatory blood pressure monitoring techniques have allowed quantification of blood pressure variations occurring over a 24 hour time. The evaluation of these phenomena has not only allowed us to investigate the mechanisms responsible for cardiovascular regulation, but it has also provided information of clinical value. In particular there is evidence that blood pressure variations are significantly related to cardiovascular complications of hypertension. Progress in technology may allow us to extend these observations by means of non-invasive continuous blood pressure recordings to all those conditions where intra-arterial methods are not allowed. PMID- 1630072 TI - Baroreflex control of regional vascular resistances during simulated orthostatism. AB - Orthostatic stress or moderate hypovolemia was simulated in 10 healthy volunteers by the lower body negative pressure technique (LBNP at -10, -20 and -40 mm Hg). LBNP induced a progressive and parallel decrease in central venous pressure and cardiac output but mean arterial pressure remained unchanged regardless of the LBNP level. Heart rate and pulse pressure were only significantly increased and decreased at LBNP -40 mm Hg, respectively, indicating that cardiopulmonary baroreflexes were selectively deactivated up to LBNP -20 mm Hg, whereas both cardiopulmonary and arterial baroreflexes were deactivated at LBNP -40 mm Hg. The LBNP-induced increase in total peripheral resistance was heterogeneously distributed within the body. Forearm vasoconstriction occurred at low levels of LBNP and was exclusively related to an increase in sympathetic tone. Splanchnic vasoconstriction also occurred at low levels of LBNP, but was related to activation in sympathetic and renin-angiotensin systems. Renal vasoconstriction occurred mainly at high levels of LBNP (-40 mm Hg), but glomerular filtration rate and filtration fraction increased at low levels of LBNP (-10 mm Hg). Thus, if renal vascular resistance is not of major importance for the control of blood pressure during orthostatism or moderate hypovolemia, neurohumoral mechanisms triggered through deactivation of cardiopulmonary receptors play a key role in the maintenance of intrarenal homeostasis associated with reduction in cardiac filling pressure. PMID- 1630073 TI - Sympathetic innervation of renal and extra-renal arterial vessels. AB - The innervation of arterial vessels has been analyzed using serial thin sections examined in the electron microscope. Sympathetic postganglionic noradrenergic axons have been found to make neuromuscular junctions on the outermost cells of the media of virtually all muscular arterial vessels with diameters between 20 microns and 1 mm in rat, rabbit and guinea pig. Junctions are formed by the majority of varicosities which are not covered by Schwann cell on the side towards the artery surface. The junctions resemble those on skeletal muscle fibers, having a single layer of basal lamina in the synaptic cleft. Although post-junctional specializations have not been identified, 15 to 20% of junctions show electron dense regions of the prejunctional membrane with associated clumps of synaptic vesicles. The form of the varicose axons differs, and three distinct types have been distinguished on morphological grounds. Two of these occur in the juxtaglomerular region of the kidney, with characteristic distributions of junctions which differ between the afferent and efferent arterioles. The presence of numerous close junctions has revolutionized our thinking about how sympathetic neuroeffector transmission occurs in arterial vessels. PMID- 1630074 TI - Arterial hypertension and aneurysmal dilatation. AB - Hemodynamic parameters and especially systemic hypertension are considered to be significant factors in the progression of aortic aneurysmal dilatation. We have recently described an original experimental model of aortic aneurysm induced by transparietal infusion of elastase in the rat abdominal aorta. In order to evaluate the effect of hypertension on the aneurysmal remodeling of the arterial wall induced by perfusion of elastase activity, this experimental model was applied to renovascular hypertensive (N = 17), spontaneously hypertensive (N = 18) and normotensive rats (N = 17). The aneurysms were induced by infusion of 15 units of hog pancreatic elastase of a one centimeter isolated aortic segment in anesthetized rats which were sacrificed two weeks later. The aneurysmal length and diameter were measured in vivo using a micrometer in a surgical microscope. The aortas were then fixed in formalin and embedded in paraffin for standard histological study. The animals which died during the experimental period were examined. All rats presented a macroscopic aneurysm two weeks after the infusion of elastase. Histologically, the aneurysmal area was characterized by the disappearance of the normal elastic network and by the presence of a collagenic wall. The dimensions of the aneurysms (transversal diameter and length) were greater in hypertensive than in normotensive animals (F = 11, P less than 0.001) and aneurysmal dimensions were positively correlated with the level of blood pressure (r = 0.56, P less than 0.001). Moreover, the frequency of aortic rupture was greater in renovascular hypertensive (4/17) than in spontaneously hypertensive (1/18) and normotensive (0/17) rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630075 TI - Effects of monohydroxylated fatty acids on arterial smooth muscle cell properties. AB - The hydroxylated derivatives of polyunsaturated fatty acids may be potent modulators of basic biological responses involved in pathological processes, including atherosclerosis. The object of the present investigation was to study the effects of monohydroxylated fatty acids (namely 12-HETE) on the properties of aortic smooth muscle cells (SMC) in culture. The changes in cell expression of differentiation antigen alpha-SM actin and 2P1A2 was followed by computerized morphometry, using specific monoclonal antibodies and the activation of cells by measuring cell motility. In addition, intracellular [Ca2+]i mobilization and IP3 formation were studied. Finally, the metabolic routes of monohydroxylated compounds and their effects on PGI2 secretion were reported. The results demonstrate that 12-HETE is able to stimulate the phenotypic modulation. PGI2 production and motility of arterial SMCs, despite any detectable activity in increasing [Ca2+]i or IP3 formation. By contrast with parent compounds 15-HETE and 13-HODE, which appear as potent prodifferentiating molecules, 12-HETE is specifically metabolized via a 10-11 reductase pathway in addition to the classical beta-oxidation pathway. Taken together, our results suggest that cellular metabolism of 12-HETE, produced by platelets in the vicinity of the arterial intima, and also by cells present inside the atherosclerotic intima, or associated with modified LDL may play a key role in the atherosclerotic process. PMID- 1630076 TI - Regulation of membrane phospholipid metabolism in heart cell culture. AB - We have isolated, from newborn rats, heart cultures enriched in contractile muscle cells (M) and cultures of fibroblast-like cells (F). M cultures respond to simulated ischemia by an arrest of beating activity, by a decrease in beta oxydation rate, ATP and phosphocreatine content and by a loss of membrane phospholipids associated with neutral lipids accumulation. F cells in contrast do not respond to oxygen deprivation. Firstly, we observed that cocultures of M and F cells respond to oxygen deprivation by an arrest of beating activity and a decrease in cellular ATP content, but failed to exhibit any significant loss of membrane phospholipids. Secondly, we demonstrated that culture medium conditioned by F cells is able to inhibit the reaction of M cells to simulated ischemia thus suggesting that fibroblasts produce a diffusible factor able to block phospholipase activation. Heat treatment and trypsinisation failed to abolish this activity, indicating that the phospholipase inhibitory factor is probably not a polypeptide. PMID- 1630077 TI - Central monoamine neurons and cardiovascular control. AB - This review discusses the cardiovascular actions of central noradrenergic and serotonergic neurons, particularly with respect to the mechanism of action of the centrally acting antihypertensive agents clonidine, methyldopa (alpha-MD) and rilmenidine. The predominant actions of the noradrenergic neurons in the brainstem are to inhibit vasomotor and cardiac sympathetic activity and to facilitate cardiac vagal responses. By contrast the serotonergic neurons in the brainstem increase blood pressure and heart rate through excitation of cardiac and vasomotor sympathetic pathways and inhibition of the cardiac vagus nerve. The centrally acting antihypertensive drugs clonidine, rilmenidine and alpha-MD activate these noradrenergic pathways and inhibit the serotonergic pathways. Noradrenergic projections to the spinal cord tonically inhibit while the serotonergic neurons facilitate sympathetic vasomotor tone. In combination with other spinally projecting pathways, these monoamine fibers form part of a high gain control system for responding to changes in specific afferent information. However, the spinal pathways do not contribute to the actions of clonidine or alpha-MD. The forebrain noradrenergic projections are important for the noradrenergic baroreflex vagal facilitation produced by acute 6-OHDA and methyldopa, but not clonidine. By activating this forebrain pathway methyldopa minimises the baroreflex compensation that might normally be expected following a reduction in blood pressure. PMID- 1630078 TI - The cytoskeleton of arterial smooth muscle cells during human and experimental atheromatosis. AB - Smooth muscle cells (SMCs) implicated in the human atheromatous process show dedifferentiated features characterized by typical changes of cytoskeletal elements. In the normal media, quiescent SMCs express predominantly the alpha smooth muscle (SM) actin isoform. In the human atheromatous plaque, and in rat experimental intimal thickening 15 days after balloon-induced endothelial injury, a decrease of the alpha-SM actin isoform and a predominance of the beta cytoplasmic actin isoform develop. Proliferating SMCs in vivo assume fetal phenotypic features which are also observed in cultured SMCs. Thus, the study of cytoskeletal changes allows a better definition of SMC phenotype. Furthermore, in vitro SMCs may represent a useful experimental model to study phenotypic modifications of SMCs during the pathological process. Cytokines and growth factors, released by cells present in the atheromatous plaque, and extracellular components of the arterial wall, such as heparin, modulate the expression of alpha-SM actin in cultured SMCs and represent good candidates to exert important regulatory actions in vivo. A better understanding of the mechanisms leading to cytoskeletal modifications may help in the clarification of the mechanisms playing a role in the development of arterial pathological events. PMID- 1630079 TI - Dietary salt and risk factors for cardiovascular disease. AB - Sodium restriction by 50 to 100 mmol/day in populations with intakes averaging 150 to 180 mmol/day would likely lead to a reduction of population mean blood pressures, and less of a tendency for blood pressures to rise with age. Fewer people would require antihypertensive drug therapy, and those who did would require less drugs. The extent of any blood pressure fall would be greatest in the elderly or those with established hypertension. A corresponding reduction in stroke incidence might be anticipated, with less certain effects on coronary deaths and diseases. Other factors, such as weight control, alcohol moderation and increased physical activity, may be of greater importance in preventing hypertension in many populations, while cessation of smoking, control of obesity, increased physical fitness and reduction in dietary saturated fat consumption should probably receive the highest priority in terms of overall reduction in the risk of atheromatous cardiovascular disease. In countries such as Japan, which has a relatively high incidence of stroke and a low incidence of coronary disease, a high sodium intake assumes relatively greater importance, in conjunction with obesity and alcohol, as a risk factor for cerebrovascular disease. PMID- 1630080 TI - [Antibacterial and immunocorrective therapy of diffuse purulent peritonitis]. AB - The effectiveness of surgical treatment of 193 patients with generalized purulent peritonitis was analysed. The complex of bacteriologic and immunologic investigations contributed to optimization of antibacterial and immunocorrective therapy. Rational antibacterial therapy should be based on the principle of the use of broad and super-broad spectrum antibiotics with mandatory inclusion into the programme for treatment of metronidazole, administration of antibacterial agents before, at the time and after the operative intervention before identification of microflora and determination of its sensitivity to antibiotics. The therapeutic and tactical approach developed permitted to reduce lethality in generalized purulent peritonitis from 39.5 to 24.9%. PMID- 1630081 TI - [Informativeness of the methods of early clinical laboratory diagnosis of acute pancreatitis]. AB - In 92 patients with acute pancreatitis, the informative value of the available methods for laboratory investigations (general blood analysis, biochemical blood analysis with measurement of the level of total protein, bilirubin, glucose, ALAT, ASAT, amylase activity, amylase activity in the urine) was analysed. The authors consider that the indices studied are rather informative for independent reliable diagnosis of acute pancreatitis and differentiation of its forms. PMID- 1630082 TI - [A comparative study of changes in suture materials in mammary gland tissues]. AB - In the experiment on 75 white rats, the reactogenicity and strength of catgut, dexon, kacelon and PGL (native analogue of vicryl) were studied 10, 20 and 30 days after their implantation into parenchyma of the lactating mammary gland (MG). Around a catgut thread, the cellular-tissue reaction according to the type of purulent inflammation occurred. A danger of oncogenic effect of catgut which manifested itself in proliferation and atypical hyperplasia of epithelium of the MG ducts was noted. Dexon, kacelon and PGL were characterized by similar low reactogenicity, but kacelon strength reduced considerably in moistening. Dexon and PGL due to their reactogenicity and strength properties are the materials of choice in surgical treatment of MG diseases. PMID- 1630083 TI - [Use of laser irradiation for the prevention and treatment of complications following surgery of the lungs and pleura]. AB - Low-energy laser irradiation was used in treatment of 77 patients with surgical diseases of the lung and pleura. Laser therapy was performed by means of transcutaneous irradiation of the patients with the use of a semiconductor arsenide-gallium laser and influencing with helium-neon laser on the biologically active points. The use of laser therapy contributed to decrease in incidence of postoperative complications, shortening the duration of treatment of the patients at a hospital. PMID- 1630084 TI - [The role of sensitization of the body in the development of experimental peritonitis]. AB - In the experiment, a role of preliminary sensibilization of an organism in increasing the reproducibility of a peritonitis model was not confirmed. A tendency for reduction in spreading of infection in the organism of animals in their intraperitoneal contamination depending on increase in a titer of specific antibodies and augmentation of activity of neutrophil granulocytes was revealed. PMID- 1630085 TI - [A method of modeling strangulation ileus]. AB - A method for modeling of strangulation ileus consisting in passing the intestinal loop through a strip of cycle rubber nipple with a diameter of 2 mm, width of 4 mm is suggested. Advantages of the method were confirmed by the findings of angioscopy and morphologic study in ileus modeling in 175 rats. The method suggested permits easy and prompt creation of a standard model of strangulation ileus in rats in all the cases, and study after the nipple transection of the changes characteristic of the postischemic period. PMID- 1630086 TI - [Surgical tactics in perforated stomach and duodenal ulcers]. AB - The results of treatment of 410 patients with a perforated gastric and duodenal ulcer were summarized. A dependence of lethality and type of the operation performed on time elapsing from the moment of perforation, presence of concomitant diseases is shown. PMID- 1630087 TI - [A method of peritoneostomy for treating diffuse purulent peritonitis]. AB - For improvement of exudate outflow and prevention of the development of abscesses, a modified method of peritoneostomy has been suggested and successfully used in treatment of 59 patients. After elimination of a source of peritonitis and sanitation of the abdominal cavity, the greater omentum is covered with a hydrocellulose film of corresponding sizes, rolled up as a rouleau, and placed in the epigastrium. The intestinal loops are covered with a perforated polyethylene film sutured to the ends of a laparotomy wound. PMID- 1630088 TI - [Surgical tactics in acute gastrointestinal hemorrhage]. AB - The results of treatment of 595 patients with acute gastro-intestinal bleeding are presented. Ulcer disease is the most frequent cause of bleeding. In its diagnosis, the use of gastroduodeno-fibroscopy is effective. In ineffective conservative therapy, the operative intervention is indicated. PMID- 1630089 TI - [The use if low-stream membrane hemoxygenation and exchange plasmapheresis in the complex treatment of patients with peritonitis]. PMID- 1630090 TI - [Laparocentesis as a method for early diagnosis and active dynamic observation in acute surgical pathology under the conditions of a district hospital]. AB - The results of the use of laparocentesis in 75 patients for the period of 6 years were summarized. As a method for early diagnosis, laparocentesis was used in sufferers with isolated, or associated trauma to the abdomen, severe polytrauma, in absence of consciousness at the state of shock, or alcohol intoxication, and as well in patients with acute surgical pathology requiring the emergency operative intervention at difficult for diagnosis situations. Reliability of the method was 97.3%. Laparocentesis performance permitted to diagnose promptly damage to the visceral organs in trauma and establish necessity to use the urgent operation in patients with signs of acute abdomen. PMID- 1630091 TI - [Bacteriologic methods of study in acute appendicitis]. AB - In the article, the results of bacteriologic study of effusion from the abdominal cavity in 137 patients with acute appendicitis are summarized. A value of bacterioscopy in urgent diagnosis of the inflammatory agent has been established. PMID- 1630092 TI - [Indications for relaparotomy in acute postoperative intestinal obstruction]. AB - For the period of 1977-1987, operations on the abdominal organs were performed in 13,306 patients. Of them, 115 (0.86%) developed 1 to 21 days after the operation acute ileus requiring the performance of emergency relaparotomy. Lethality in this complication was 33.9%. A retrospective analysis of 103 case records and observations on 12 patients who underwent at the early postoperative period emergency laparotomy for acute ileus were performed. The data were entered on a formalized card. The material was processed by means of a computer. The integral criteria for diagnosis of acute postoperative ileus which permitted to predict with an accuracy of 99% the complication serving an indication for relaparotomy were developed. PMID- 1630094 TI - [Choice of the approach in the performance of reconstructive surgery of the abdominal aorta]. AB - The experience with surgical treatment of 630 patients with the use of extraperitoneal and transabdominal approaches to the abdominal aorta is summarized. Their advantages and disadvantages are noted. The expediency to use a new extraperitoneal approach to suprarenal and infrarenal portions of the abdominal aorta has been proved. The results of a topographic-anatomic study are presented. The technique for performance of a new approach to the abdominal aorta at this region, its advantages over the existing approaches are described. PMID- 1630093 TI - [Diagnosis and surgical tactics in severe closed injury to the abdomen]. AB - The authors observed 139 patients with severe closed abdominal trauma. Diagnosis of the injuries mentioned is often difficult. Performance of laparoscopy permits to establish correct diagnosis. Severity of the state is conditioned by extensive character of injury to the viscera, presence of traumatic shock and internal hemorrhage. Lethality in closed abdominal trauma is 3.6%. PMID- 1630095 TI - [Experience in the organization of specialized surgical care of a patient with acute gastrointestinal hemorrhage under the conditions of a district hospital]. PMID- 1630096 TI - [Organization and experience of the work of an daycare surgical hospital]. PMID- 1630097 TI - [Postoperative peritonitis]. PMID- 1630098 TI - [Spontaneous rupture of the esophagus]. PMID- 1630099 TI - [Perforation of the urinary bladder by a foreign body complicated by diffuse peritonitis]. PMID- 1630100 TI - [A method of treating peritonitis]. PMID- 1630101 TI - [A method of circulating irrigation of the abdominal cavity in peritonitis]. PMID- 1630102 TI - [Acute intestinal obstruction caused by a surgical napkin]. PMID- 1630103 TI - [A combination of acute perforated appendicitis and pancreatic necrosis]. PMID- 1630104 TI - [A case report of acute diverticulitis and acute appendicitis]. PMID- 1630105 TI - [A rare complication of appendectomy]. PMID- 1630106 TI - [A combined wound of the heart, lung and colon]. PMID- 1630107 TI - [Severe closed trauma to the abdomen with complete circular avulsion of the stomach from the duodenum, and rupture of the spleen and esophagus]. PMID- 1630108 TI - [A rare case of a thoracoabdominal wound]. PMID- 1630109 TI - [Traumatic rupture of the right main bronchus]. PMID- 1630110 TI - [Tactics for treating acute intestinal obstruction]. AB - Performance of infusion-transfusion therapy before the operation, suboperative intravenous administration of antibiotics, metrogil, sanitation of the abdominal cavity with the use of antiseptics, performance of transnasal intraoperative intubation of the small intestine, Hartmann operation in patients with cancer of the left colon complicated by acute ileus (AI), liquidation of ileus at operation permitted considerable improvement of treatment of the patients with AI. The incidence of postoperative complications reduced from 9.7 to 4.1%, lethality- from 12.6 to 5%. PMID- 1630111 TI - [Continuous electrocardiostimulation in a patient with incarcerated inguinal hernia]. PMID- 1630112 TI - [A chylous cyst of the abdominal cavity]. PMID- 1630113 TI - [Plastic surgery of a duodenal defect at the time of a right-sided hemicolectomy]. PMID- 1630114 TI - [Diagnosis of invagination of the small intestine in adults]. PMID- 1630115 TI - [An incomplete turn of the small intestine in adults]. PMID- 1630116 TI - [Personnel bottlenecks in the Zurich University Hospital. At the borders of peak medicine]. PMID- 1630118 TI - [Escaped from torture]. PMID- 1630117 TI - [Relations between fathers and their newborns]. PMID- 1630119 TI - ["Flight is impossible ...". Interview by Martin Glauert]. PMID- 1630120 TI - [Communication between psychogeriatric patients and their caregivers. Beyond words ...]. PMID- 1630121 TI - [An evaluation instrument: the RAI--Resident Assessment Instrument]. PMID- 1630122 TI - [Urinary incontinence in women of over 50 years. A tabu that ought to disappear]. PMID- 1630123 TI - [Questions concerning the new regulations in nursing education. Removing concerns]. PMID- 1630124 TI - ["We ourselves should know where we want to go". Interview by Monika Brechbuhler]. PMID- 1630125 TI - ["Pain and suffering of the dying"--a lecture. With love and honesty]. PMID- 1630126 TI - [How to help children to deal with painful interventions]. PMID- 1630127 TI - [Looking back: on the essence of pain]. PMID- 1630128 TI - [Nursing of patients with chronic pain--a term paper. What nurses can do]. PMID- 1630129 TI - [Model of ambulatory pediatric nursing. We are nursing children at home]. PMID- 1630130 TI - [My work place. On my way in matters of health promotion]. PMID- 1630132 TI - [Close and partners]. PMID- 1630131 TI - [Pain/suffering: Alice through the looking glass]. PMID- 1630133 TI - Managing the wear and tear of dentistry. PMID- 1630134 TI - Blood pressure monitoring: a necessary routine? AB - While faculty in Oral Medicine Departments have advocated routine blood pressure monitoring for more than thirty years, the activity does not seem to be routine in many practices, but rather undertaken only when the patient indicates that there is a problem. This study was undertaken to ascertain if the frequency of abnormal blood pressure findings warrants routine monitoring on the patient who is already being seen by a physician or who is asymptomatic. PMID- 1630135 TI - Improvement in the bond strength of phosphate ester bonding systems to dentin surfaces. PMID- 1630136 TI - Special ethical issues in the management of PVS patients. PMID- 1630137 TI - The morality of physician-assisted suicide. PMID- 1630138 TI - Voluntary euthanasia and the risks of abuse: can we learn anything from The Netherlands? PMID- 1630139 TI - Mistakes and fraud in medical research. PMID- 1630140 TI - Germ-line gene therapy: a new stage of debate. PMID- 1630141 TI - Whodunit? Causal responsibility of utilization review for physicians' decisions, patients' outcomes. PMID- 1630142 TI - Current issues in biomedical ethics. PMID- 1630143 TI - Some ethical costs of rationing. PMID- 1630144 TI - Justice, politics and community: expanding access and rationing health services in Oregon. PMID- 1630145 TI - The moral standing of animals in medical research. PMID- 1630146 TI - An axiology for national health insurance. PMID- 1630147 TI - Ethical dilemmas in HIV infection: what have we learned? PMID- 1630148 TI - Recruitment: a survey developed for dental hygiene career awareness in Louisiana. PMID- 1630149 TI - When is a worker an independent contractor? A wrong answer can bring stiff penalties. PMID- 1630150 TI - Intracellular nucleotides of lymphocytes and granulocytes from normal ageing subjects. AB - Impaired lymphocyte and granulocyte function in the aged may, in part, reflect intrinsic aged-related biochemical alterations. In this study we compared the ribonucleotide contents of lymphocytes and granulocytes from young and old subjects evaluated by means of an HPLC-anion exchange method. We found that in general both populations from old subjects present higher levels of the various nucleotides, in particular: ATP, UDP, CTP, UDP-glucose in granulocytes, AMP, CTP, UDP-N-acetylglucosamine, UDP-glucose in lymphocytes. These data suggest that these molecules accumulate in aged subjects because of altered biochemical pathways. The increased pool of UDP-sugars, in particular, could be due to a depressed activity of some glycosyltransferases which therefore fail to glycosylate some plasma membrane cell proteins, thus accounting for their functional impairment. PMID- 1630151 TI - Correlation of age-associated increases in follicle stimulating hormone secretion with decreases in antral follicles: failure of progesterone-induced acyclicity to prevent these changes. AB - It is well known that the number of follicles in the mammalian ovary decreases with age. In light of previous data from this laboratory showing age-related alterations in the secretion and production of follicle-stimulating hormone (FSH) in rats by 5-6 months of age, one objective of the present study was to determine if alterations in FSH secretion were accompanied by changes in the number of antral follicles. A second objective of this study was to determine whether or not interruption of cyclic activity by continuous progesterone (P) treatment could decelerate age-associated changes in FSH secretion possibly by retarding the depletion of follicles through ovulation. For this study, one group of 4-day cycling, 7-week-old rats received one empty Silastic implant while another group received 3-40 mm implants containing 30 mm crystalline P. Implants were replaced every 2 weeks until the animals were 5 months old. Progesterone-implanted rats were acyclic during treatment exhibiting predominantly leukocytic vaginal smears. Regular 4-day cycles resumed when P implants were withdrawn (rats approximately 5 6-months-old). A group of 2-3-month-old untreated rats were used for comparison. As expected from our previous results, serum FSH levels at 1600 h on estrus were significantly higher in 5-6-month-old rats receiving empty capsules than in younger rats. Serum FSH concentrations measured in P-treated rats at this time also were significantly higher than levels of this gonadotropin measured in younger rats. Ovaries of older control and P-treated rats contained significantly fewer medium and large antral follicles (greater than 250 microns) than the ovaries of younger rats despite the curtailment of estrous cyclicity and ovulation by continuous P treatment. Interestingly, P treatment prevented the age associated decrease in thymus weight. Taken together, the present observations suggest that a decrease in the number of growing follicles may be a factor contributing to early age-related alterations in FSH secretion. Furthermore, the prevention (at least temporarily) of age-related thymic involution by P treatment may be indicative of an interrelationship between thymic and reproductive aging. PMID- 1630152 TI - Effect of ethinyl estradiol treatment on lipoproteins and LCAT activity in aged rats. AB - The induction of hepatic lipoprotein (apo B/E) have been investigated in Fischer 344 rats. These studies were aimed to determine the mechanism underlying the previously observed (Lee et al., Mech. Ageing Dev., 61 (1991) 85-98) hypercholesterolemia and the age-related decrease in the fractional rate of endogenous cholesterol esterification. Young (5 months) and aged (22 months) male Fischer-344 rats were treated with pharmacological doses (5 mg/kg per day) of ethinyl estradiol (EE) for 7 days. Reduction of plasma cholesterol (57% in young vs 47% in aged rats) and high density lipoprotein cholesterol (64% in young vs 63% in aged rats) occurred in both groups upon EE treatment. Initial low density lipoprotein levels were very low in the plasma of young rats and consequently were not affected by EE treatment. However, in aged rats, the low density lipoprotein levels were much higher initially and were markedly reduced by EE treatment. (18.0 vs 10.0 mg/dl). Very low density lipoproteins were about the same initially but increased in aged rats and decreased in young rats upon EE treatment. Both the lecithin:cholesterol acyltransferase (LCAT) activity (as determined with a proteoliposome substrate) and the fractional rate (FR) of the endogenous cholesterol esterification decreased in treated animals compared to controls. However, the differences in the FR of the endogenous cholesterol esterification between young and aged rats (observed before treatment) were nearly abolished upon treatment. These data suggest that the previously observed age related decrease in the FR of endogenous cholesterol esterification is due to the accumulation of apolipoprotein E-rich (apo E) lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630153 TI - Quantitative evidence that the genetic basis of human mortality operates at the translation level: a preliminary assessment. AB - The dying off of human population cohorts due to different age related diseases rigorously follows stochastically derived rules. The existence of such rules suggests a common, fundamental mechanism for human mortality. We show here, by a simple quantitative analysis, that the progressive loss with age of genetic triplet code information (anticodons) in body cells, as described by the statistics of extremes in order theory, serves as such a mechanism. PMID- 1630154 TI - Longitudinal Gompertzian analysis of emphysema mortality in the US, 1962-1987: the differing basis for evolving mortality patterns in men and women. AB - Age-specific mortality rates for emphysema in the United States from 1962 through 1987 were subjected to longitudinal Gompertzian analysis, a method that can be used to identify and distinguish aggregate genetic, environmental, and competitive influences upon mortality. Annual crude emphysema mortality rates (per 100,000) among men increased from 11.77 in 1962 to 20.94 in 1968, and then fell to 7.74 in 1987. The basis for this rise and fall is shown to be the corresponding changes in environmental influences upon emphysema mortality in men. Between 1962 and 1987, the annual crude emphysema mortality rates among women increased from 1.71 to 4.25. The basis for the increase of emphysema mortality in women, on the other hand, is shown to be an enhancement of the competitiveness of emphysema as a cause of mortality in women, and not the result of worsening environmental influences. The capability to distinguish between environmental and competitive influences upon evolving human mortality patterns could have a significant impact upon public health policy. PMID- 1630155 TI - Phytohemagglutinin induced changes of membrane lipid packing, c-myc and c-myb encoded protein expression in human lymphocytes during aging. AB - Three parameters which signal different stages of cell activation were analyzed in lymphocytes from young and old subjects. Merocyanine 540 (MC-540) incorporation into the membrane lipid phase was used as a very early marker of activation and was measured after 1 h of phytohemagglutinin (PHA) stimulation. The proteins coded by c-myc and c-myb protooncogenes were determined by appropriate antibodies and were taken as markers of the G0/G1 and G1/S phase transition, respectively. The number of cells which increased the uptake of MC 540 following PHA stimulation did not differ when comparing young and old individuals. Both the number of the responding cells and the size of the response were decreased during aging when the presence of the c-myc protein was taken into account. A consistent decrease of the percentage of lymphocytes able to express the c-myb protein was observed in the cells from old donors as compared to those from the young ones, but the amount of detectable protein per cell remained unchanged. Our data suggest that the deficiency of responsiveness which accompanies aging is due to impairments at different points of the cell cycle. The very low number of cells expressing the c-myb protein is likely the result of step by step elimination of those cells not able to fulfill the requirements to progress along the cell cycle. PMID- 1630157 TI - Longitudinal Gompertzian analysis of ALS mortality in England and Wales, 1963 1989: estimates of susceptibility in the general population. AB - Mortality statistics in amyotrophic lateral sclerosis (ALS), which is more commonly and generally termed motoneurone disease (MND) in the United Kingdom, have been shown to reflect the incidence of previously diagnosed cases of the disease in a more complete way than in other conditions [1,2]. An analysis of changing patterns of mortality may therefore be a particularly appropriate way of tracing the underlying trends in the disease and is in principle a useful way of investigating the relationship between environmental and genetically controlled factors in the genesis of the condition. The majority of analyses so far have concentrated on the crude rise in reported mortality rates evident in recent decades in a number of countries [2-5], on the uneven geographical distribution [6,7] and on the complex range of plausible causes for these reported rises. Debates have centred on whether the increases represent 'real' or 'artifactual' changes, with no apparent resolution of the issue [8,3]. Recently Riggs [9] proposed a novel way of analysing this issue by using a Gompertzian model and provided evidence of the existence of an inherently susceptible subset of the US population. Riggs indicated that while the rise in ALS mortality is real, it is for the most part the result of an increase in the size of this inherently susceptible sub-population due to greater longevity. In order to examine the wider applicability of a Gompertzian model to ALS the technique has been replicated with the mortality rates for England and Wales for the 27-year period from 1963 to 1989. The technique has been developed and extended to produce an estimate of the size of the inherently susceptible sub-population (both male and female) over the entire period. PMID- 1630156 TI - Hepatic cytochrome P-4503A (CYP3A) activity in the elderly. AB - Elderly patients exhibit decreased clearance of multiple drugs biotransformed by the hepatic cytochromes P-450. The cytochromes P-450 are a superfamily of enzymes, which comprise a central component of phase I drug metabolism. Distinct isoforms metabolize specific drugs. In human liver microsomes, the glucocorticoid inducible cytochrome P-450IIIA, CYP3A, catalyzes the N-demethylation of erythromycin. To examine the activity of hepatic CYP3A in elderly males and females, erythromycin N-demethylation was examined, as reflected by the recently described [14C]erythromycin breath test in 24 healthy volunteers, age 70-88. The [14C]erythromycin breath test was measured in normal elderly males and females to: (a) determine persistence of the gender-related dimorphism (evident in younger subjects) of CYP3A activity in the elderly population, (b) examine the effect of % ideal body weight, age, diet, and medication use on the activity of human hepatic CYP3A, and (c) compare breath test results obtained in normal geriatric volunteers with published results obtained in younger subjects, to determine aging-related alterations in CYP3A enzyme activity. Erythromycin N demethylation varied fivefold among these patients. Similar to earlier studies examining erythromycin N-demethylation in younger subjects, CYP3A activity was found to vary with gender in the geriatric cohort. [14C]Erythromycin N demethylation at 60 min was 3.14% +/- 0.75 (n = 13) in females and 2.15% +/- 0.77 (n = 11) in males (P = 0.005). In evaluating the role of % ideal body weight and % dietary fat using multivariable linear regression analyses, [14C]erythromycin N demethylation, was found to decline significantly as % ideal body weight increased (P = 0.001). This was not confounded by gender. [14C]Erythromycin N demethylation was not related to dietary fat intake (P less than 0.13). [14C]Erythromycin N-demethylation in the elderly volunteers was similar to values reported for subjects aged 20-60. Performance of a new non-invasive test of the human hepatic glucocorticoid-inducible CYP3A in a geriatric cohort suggests that: (a) the gender-related heterogeneity in function of the glucocorticoid inducible human CYP3A persists during normal aging, (b) that the activity of CYP3A may decrease in obesity, and (c) that the activity of CYP3A is stable throughout normal ageing. PMID- 1630158 TI - Changes in glutathione content and localization in rat heart as a function of age. AB - The influence of aging on glutathione levels and distribution in the heart was studied in male Sprague-Dawley rats of 3 (young), 12 (adult) and 24 (old) months of age using biochemical and histofluorescence techniques, respectively. Biochemical assays of reduced glutathione (GSH) in the right and left ventricles and in the septum showed a significant decrease in GSH levels in adult in comparison with young animals. No further changes were noticeable between adult and old rats. GSH histofluorescence revealed a rather homogeneous distribution of the product of histochemical reaction within both right and left atria in 3-month old rats. In 12-month-old rats a reduction of GSH histofluorescence in comparison with younger animals was noticeable. The loss is more consistent in the epicardial portion of the right atrium and in the endocardial region of the left atrium. In the atria of 24-month-old rats GSH reactivity was homogeneously distributed throughout the atrial wall and was significantly lower than in young or adult rats. In 3-month-old rats GSH histofluorescence was slightly lower in the epicardial than in the endocardial portions of both ventricles. In adult rats a significant decrease of GSH histofluorescence was noticeable in comparison with 3-month-old rats. The loss is particularly pronounced within the endocardial region of the left ventricle. In 24-month-old rats GSH histofluorescence showed no significant differences between adult rats. However, GSH was more homogeneously distributed throughout the ventricular wall than in adult animals. The significance of these data is discussed in relation to the role that GSH plays in protecting the myocytes against free radical damage. PMID- 1630159 TI - Effect of dietary restriction on lysosomal bodies and total protein synthesis in hepatocytes of aging rats. AB - The accumulation of lysosomal bodies has long been considered to be an important correlate of aging. However it is not well established whether these age related changes interfere with cellular function. In this study, an evaluation of lysosomes by ultrastructural analysis was performed in livers of 4-6 and 20-24 month-old Sprague-Dawley female rats, fed ad libitum (A) or a restricted diet (R). An attempt was made to relate this parameter to hepatic protein synthesis, a liver function known to decrease with age and increase with dietary restriction. Aging was accompanied in both A and R animals with higher number and size of secondary lysosomes (lipofuscin) and by a decrease in total protein synthesis in hepatocytes. When compared to age matched ad libitum fed animals, livers of food restricted rats contained higher number of secondary lysosomes, yet exhibited higher protein synthetic capacity. Thus in hepatocytes, lipofuscin accumulation does not seem to interfere with cellular function. PMID- 1630160 TI - Catecholaminergic nucleus tractus solitarius lesions in anesthetized rats alter baroreflexes differently with age. AB - To explore whether catecholaminergic lesions produced chemically in the nucleus tractus solitarius (NTS) would alter the baroreflex impairment that normally occurs with age, we compared baroreflex responses in 3- and 14-month-old rats given bilateral microinjections of 6-hydroxydopamine (6-OHDA) or its vehicle into the NTS. After 2 weeks, basal pressures were unaffected but heart rates were lower in 14- than in 3-month-old rats. Sympathetic nerve inhibition elicited reflexly during intravenous infusions of sodium nitroprusside was reduced in 3 month-old rats, but increased in 14-month-old rats. Depressor, bradycardiac, and sympatho-inhibitory responses to afferent aortic nerve stimulation were likewise reduced in 3-month-old rats and oppositely enhanced in 14-month-old rats. Enhanced bradycardia probably does not depend on increased parasympathetic sensitivity because responses to vagal stimulation did not differ between age groups. Although underlying mechanisms remain uncertain, by showing that baroreflex responses become altered differently in 3- and 14-month-old rats by 6 OHDA these results suggest that the baroreflex changes normally occurring with age may be due, at least in part, to modified catecholaminergic mechanisms in the NTS. PMID- 1630161 TI - Quantitation of changes in mitochondrial DNA during aging and regeneration of rat liver using non-radioactive DNA probes. AB - By using DNA probes prepared from cloned cells which contain mitochondrial DNA (mtDNA) sequences in plasmids, the specific detection of mtDNA became possible in the presence of large excess of nuclear DNA by DNA-DNA hybridization. For this purpose, we prepared mtDNA probes labeled with non-radioactive substrate, which allowed a wider possibility of application. This method revealed that the contents of mtDNA in rat liver are strikingly decreased during aging. Furthermore, it was observed that although mtDNA content increased upon partial hepatectomy even in old rats, it decreased to the pre-operation level rather rapidly within 1 week after reaching peak in regenerated liver. PMID- 1630162 TI - Differential expression of membrane polypeptides on fetal thymic stroma co cultured with bone marrow cells from young and old mice. AB - Cell membrane polypeptides from co-cultures of lymphocyte depleted fetal thymuses (C57BL/Ka, H-2b, Thy 1.1) and bone marrow (BM) cells (C57BL/6J, H-2b, Thy 1.2) were analyzed by two-dimensional gel electrophoresis (2D-PAGE). Donors of BM cells were young (3 months) and old (24 months) mice. Two polypeptides, not detected in either the alymphoid thymus itself or the BM cells prior to seeding, were expressed in the co-cultures, and their levels in the presence of old BM cells were higher than in the presence of young BM cells. Two other polypeptides, originally observed in the thymic stroma, exhibited reduced levels by day 3 in cocultures containing BM cells from young donors, but not from old donors. It is concluded that distinct changes in membrane proteins are manifested in the thymic stroma, as well as in the colonizing BM cells. PMID- 1630163 TI - [The response of the growth hormone to acute effort is a function of training]. AB - BACKGROUND: The increase of the growth hormone (GH) during exercise is known although the relationship of this response with other hormones, the type and intensity of the exercise, nutritional state and with the degree of training are reasons for discussion. The aim of this investigation was to study the response of the HG on a group of young adults with different degrees of training, according to the maximum consumption of oxygen (VO2 max) achieved over a short period of time. METHODS: Thirty-nine healthy subjects who underwent maximum effort on the treadmill were grouped according to VO2 max reached (less than 3,000 ml/min; 3,000-4,500 ml/min and greater than 4,500 ml/min). Systolic blood pressure (SBP) and diastolic blood pressure (DBP), respiratory quotient (RQ), O2 pulse, cardiac frequency (CF) respiratory equivalence (RE), glycemia, plasma insulin (PI), C peptide, lactic acid, venous pH, plasma renin activity (PRA), plasma aldosterone, thyrotropine (TSH), triodothyronine (T3), thyroxine (T4), adrenocorticotropine (ACTH), cortisol and GH were measured basally and following achievement of VO2 max. RESULTS: The GH was only increased in those subjects with a VO2 max higher than 3,000 ml/min with a significant positive correlation found between the GH and VO2 max and a significant negative correlation was found between the GH and lactic acid at the end of the test. The increase of glycemia at the end of the test correlated with the VO2 max. The PI and C peptide increased at the end of the test in the subjects with greater VO2 max capacity and correlated positively with the VO2 max and with the GH upon completion of the exercise. CONCLUSIONS: These results suggest that the response of the growth hormone to exercise is a function of maximum oxygen consumption although this only explains 24% of the variants of the growth hormone. Despite important hormonal and metabolic mobilization during exercise, no model of multiple regression has been found which substantially improves the association found between the growth hormone and maximum oxygen consumption. PMID- 1630164 TI - [Epidemiology of diabetes mellitus in the province of Leon]. AB - BACKGROUND: Diabetes mellitus (DM) is a very important health problem because of its high morbidity and mortality. The aim of the present study was to investigate the prevalence of diabetes in the adult population of the Leon province and its possible association with the most common risk factors and markers. METHODS: A cross-sectional descriptive study was designed with a multistage stratified sampling (572 individuals). A questionnaire about several sociodemographic variables, an alimentary survey, measurements of height and weight, capillary baseline glycemia, and oral glucose tolerance test with 75 g glucose were carried out. RESULTS: The observed prevalence of diabetes mellitus was 5,6% and that of glucose intolerance 10,3%. The known/unknown DM ratio was 2,2/1. The prevalence of treated DM was 1,9%. The leading variables associated with DM were age, a positive family history of diabetes and obesity. A higher incidence of DM was found in females, in urban media, and in high social classes. BACKGROUND: Diabetes had been previously underrated in the Leon province. The observed prevalence values are close to those from other methodologically similar studies. In addition, an association was found between DM and some non-modifiable risk factors (age, sex or family history); by contrast, there is a very important risk factor (obesity) which may be modified by intervention. PMID- 1630165 TI - [Treatment of esophageal candidiasis with fluconazole in acquired immunodeficiency syndrome. Comparative study of 2 therapeutic schemes]. AB - BACKGROUND: To evaluate the efficacy and pharmacological safety of 2 therapeutic trials with fluconazole in candida esophagitis in AIDS patients. METHODS: A total of 75 episodes of candida esophagitis in 70 AIDS patients were included in an open prospective study. In group I 36 patients were included who received 200 mg of fluconazole orally the first day followed by 100 mg daily for 4 weeks. In group II (34 patients) the length of treatment was reduced to 10 days with the same daily doses. Therapeutic response was evaluated by esophagoscopy, biopsy and fungal culture. RESULTS: The protocol was completed at 68 episodes with a cure being obtained in all but 2 patients in group II. No significant differences in clinical response were found between the 2 groups. The incidence of oropharyngeal colonization at the end of treatment was greater in patients from group I than from group II (43% vs 11%). Fluconazole was well tolerated in all the patients. A slight alteration of the hepatic enzymes was observed in 29 cases (40%) with a lower incidence in the shorter time group (p less than 0.001), however, treatment was discontinued only in 1 patient because of severe asymptomatic hepatic dysfunction to which a relation with the drug is unclear. CONCLUSIONS: Fluconazole in an efficient and safe agent in the treatment of candida esophagitis in AIDS patients. A 10 day treatment is a useful as longer treatment and has a lower risk of adverse effects. PMID- 1630166 TI - [Suicide attempts in patients with organic disease]. AB - BACKGROUND: The aim of the present was to study the relation between organic disease and suicidal behavior. METHODS: The characteristics of 257 patients hospitalized for medical or surgical causes following attempted suicide were studied between June 1984 and June 1990 with 45 cases previously having had physical disease being compared with 212 that had not. RESULTS: Ninety-seven percent of the attempted suicides with organic disease fulfilled the DSM-III-R criteria for some psychiatric diagnosis with affective disorders predominating (64%). Suicides with organic illness tended to be older (p less than 0.0001), present a larger number of widowed patients (p less than 0.0001), have affective disorders (p less than 0.0001), non violent modes of suicidal behavior (p less than 0.008), and have a preference for non psychotropic drugs and barbiturates (p less than 0.007). CONCLUSIONS: Patients with organic disease who make serious attempts to commit suicide are characterized by high psychiatric morbidity (97%) with a predominance in the diagnosis of severe depression. PMID- 1630168 TI - [Suicides]. PMID- 1630167 TI - [Intravesical Calmette-Guerin bacillus]. PMID- 1630169 TI - [Management of a patient with arthritis at the emergency service]. PMID- 1630170 TI - [Neoplastic hypercalcemia]. PMID- 1630171 TI - [Infection caused by human immunodeficiency virus type 1 in individuals with negative serology. Is it really frequent?]. PMID- 1630172 TI - [Course of human immunodeficiency virus infection and programs with adequate retention capacity in the control of acquired immunodeficiency syndrome and tuberculosis in parenteral drug addicts]. PMID- 1630173 TI - [Retrieval and posterior use of the data contained in a database with a computer program]. PMID- 1630174 TI - [Non-hodgkin's lymphoma with cranial involvement]. PMID- 1630175 TI - [Right to reply to the reviewer]. PMID- 1630176 TI - [Subarachnoid hemorrhage and anticoagulant treatment. Presentation of 2 cases associated with aneurysm]. PMID- 1630177 TI - [Necrotic ulcers during oral anticoagulant treatment in protein C deficiency]. PMID- 1630178 TI - [A cost-effectiveness analysis of vaccination against the hepatitis B virus]. AB - BACKGROUND: The incidence of hepatitis B is on the increase despite immunization of people susceptible to risk populations. After the introduction of a recombinant vaccine in 1986, it has become possible to evaluate different alternatives of immunization, from the point of view of efficacy, with the aim of controlling the disease. METHODS: A cost-effectiveness analysis was performed with the use of decision trees and calculation of the cost per avoided case of infection in the different strategies evaluated, vaccination to risk groups, pubescent youth, newborns, and communicated accidental exposure. An evaluation of the different alternatives was carried out in a simple model associated to a passive and active immunization program of newborns of mothers who are carriers of HbsAg and finally, the possibility of revaccination is added. RESULTS: Costs and future profits are presented in pesetas for 1990 and rates of social discounts of 4% and 7% are applied actualizing the same. For the prevalence estimated in the bibliography consulted, the cost per avoided case oscillated between 115,000 and 310,000 ptas in the most numerous risk groups (those living with carriers and ADVP) with lower covering; in massive immunization of pubescent youth the costs are from 30,000 to 130,000 ptas; the costs for newborns is of about 400,000 ptas; and accidental exposure rises to 500,000 ptas per avoided case. CONCLUSIONS: In vaccination versus the hepatitis B virus systematic vaccination of adolescents is proposed as most efficient and with the aim of disease control a program of passive and active immunization of newborns of carrier mothers should be included. PMID- 1630179 TI - [A glucose tolerance study in the 12 months postpartum in patients with gestational diabetes]. AB - BACKGROUND: It has been reported that patients with gestational diabetes have a considerable long term risk of developing diabetes mellitus. METHOD: Glucose tolerance was studied in the 12 months following birth in 155 patients diagnosed by the authors as having gestational diabetes and followed during pregnancy. RESULTS: It was observed that in 48% of the patients alterations persisted (33% glucose intolerance and 15% diabetes mellitus). Glucose tolerance during gestation and the perinatal results were retrospectively analyzed with a relation with the postpartum reclassification being observed. CONCLUSIONS: It was estimated that the percentage of alterations in glucose tolerance persisting postpartum is extremely high, suggesting the need for this test with a double objective: the reclassification of gestational diabetes and the early detection of glucose intolerance and diabetes mellitus. PMID- 1630180 TI - [Time-series analysis applied to nosocomial infection]. AB - BACKGROUND: In this study we introduce a new view of hospital infection, to apply time series techniques to it. Our objective is to complement hospital infection's epidemiological surveillance by means of obtaining alert and alarm thresholds that make easy to the epidemiologist the decision of intervention, in case they are exceeded. METHODS: We have used the classic time series analysis described by Rumeau-Rouquette, and ARIMA (Autoregresive Integrated Moving Average) models developed by Box and Jenkins. The study focus on three hospital units: one intensive care, one long term care and one surgical unit. The nosocomial infection intervals have been calculated with a 68% (1SD) and 95% (2SD) confidence levels. RESULTS: We detect an ascending general trend in the last two units, without the detection of seasonal variations. Two ARIMA (1, 0, 0) models we obtained for surgery and long term care, discarding other better adjusted models, more complex and difficult to obtain, but with no real advantage in prediction power. Confidence intervals were calculated with both methods. We did not find general trend and seasonal variations for intensive care unit. No model was considered valid, because of its high random component. The nosocomial infection intervals have been calculated with mean +/- 1SD and mean +/- 2SD. CONCLUSIONS: We think that more precise knowledge of hospital infection, with a high random component in our study, can be in addition useful to assign priority to human and material resources. PMID- 1630181 TI - [Wegener's granulomatosis, 1992]. PMID- 1630182 TI - [Clozapine, to be or not to be?]. PMID- 1630183 TI - [Wegener's granulomatosis: a report of 6 patients]. AB - The clinical and analytical manifestations and the evaluation of 6 patients diagnosed with Wegener's granulomatosis (WG) in the Germans Trias i Pujol Hospital between 1986-1990 are described. The most frequent clinical manifestation found were general and respiratory symptoms. Three patients presented an alteration in renal function and urinary sedimentation. Antibodies against the cytoplasm of the neutrophils (ANCA) detected by indirect immunofluorescence (IIF) were positive in 4 patients. All the patients underwent initial complete remission with immunodepressor treatment and one presented relapse of the disease at 19 months of diagnosis. Complications were: opportunistic infections obliging discontinuation of treatment in one patient, distal necrosis of the fingers requiring amputation in another patient and massive atelectasis of the right lung requiring pneumonectomy in a third patient. PMID- 1630184 TI - [Behcet's disease with an onset prior to the appearance of chronic myeloid leukemia]. AB - The case of a Ph-positive female patient with chronic myeloid leukemia (CML) is reported. The patient presented a cutaneous-mucous picture prior to the appearance of the hemopathy consisting of genitals ulcers, buccal aphthae and nodular cutaneous lesions the study of which demonstrated panniculitis. The lesions improved with the administration of low doses of prednisone and colchicine. The CML evolved to a blastic crisis of a monocytic phenotype at 14 months of diagnosis leading to death of the patient. The cutaneous-mucous picture was catalogued as Beccet disease (BD) according to the criteria of the International Study Group for Behcet Disease. Given the lack of serologic tests or pathognomonic histologic lesions the difficulty in the diagnosis of BD is commented upon and the differential diagnosis of this disease, particularly with respect to the Sweet syndrome, is discussed. PMID- 1630185 TI - [Cerebral infarct in a patient with systemic lupus erythematosus. The presence of lupus anticoagulant and Libman-Sacks endocarditis]. PMID- 1630186 TI - [Pheochromocytoma: an analysis of 8 cases]. PMID- 1630187 TI - [The treatment of cerebral abscesses]. PMID- 1630188 TI - [The value of fine-needle aspiration puncture as a diagnostic method]. PMID- 1630189 TI - [Chylous ascites, chylothorax and stomach cancer]. PMID- 1630190 TI - [Health care at home: who does it? From where? Why?]. PMID- 1630191 TI - [Treatment difficulty in familial homozygous hypercholesterolemia]. PMID- 1630192 TI - [Streptococcus pyogenes endocarditis secondary to cellulitis]. PMID- 1630193 TI - [Acute psychosis and biperiden]. PMID- 1630195 TI - [Alopecia, curable or incurable?]. PMID- 1630194 TI - [Capnocytophaga sepsis in a man with acute lymphoblastic leukemia]. PMID- 1630196 TI - [The value of consensus conferences]. PMID- 1630197 TI - [The norms for good clinical practice in drug trials performed in Spain. A survey of the pharmaceutical industry]. AB - BACKGROUND: The objective of this survey was to assess the state of the art of the implementation of Good Clinical Practice in the Spanish Pharmaceutical Industry. METHODS: A questionnaire was sent to the sixty first laboratories according to their sales of ethical products. In the questionnaire there were questions concerning nationality of the company, personnel in clinical research, use and characteristics of standard operating procedures (SOPs), auditing and quality assurance as well as questions in connection with the future implications of SOPs implementation. RESULTS: The level of answer was 42%. Twenty one out of the 24 companies that answered the questionnaire had SOPs implemented. In total 150 clinical research projects were carried out in 1990. One hundred one out of this 150 were performed under GCP. Fourteen companies agreed that with their current structure were able to accomplish 100% of the projects with GCP. The most frequent estimation of cost increase due to GCP was 30% (min. 10%; max. 70%). In overall 26 external audits were performed in 1990. Twenty one laboratories stated that they had not acceptance problems of GCP among the investigators. CONCLUSIONS: The sample seems to be representative of the Spanish pharmaceutical industry attitude with respect to GCP implementation. Although the exigency level was not detailed, around 42% of the clinical trials sponsored by the pharmaceutical industry are performed according to GCP. There is a positive impression as to the possibility to implement GCP as well as to the attitude of the investigators to this respect. PMID- 1630198 TI - [The cytokines that maintain living bone]. PMID- 1630199 TI - [The health-care and economic importance of the median hospital stay]. PMID- 1630200 TI - [New systems for making slides by computer]. PMID- 1630201 TI - [Pleural effusion secondary to a malignant thoracic schwannoma]. PMID- 1630202 TI - [Myelopathy secondary to electric trauma from lightning]. PMID- 1630203 TI - [Septic pneumococcal arthritis in a female patient with chondrocalcinosis]. PMID- 1630204 TI - [Hypertrophic osteoarthropathy and the human immunodeficiency virus]. PMID- 1630205 TI - [Care for the diabetic patient in Catalonia. A study of a population sample]. AB - BACKGROUND: The aim of this study was to determine the clinical and therapeutic profile of both types of diabetics (IDDM and NIDDM) attended at different levels of health care in Cataluna in order to establish quality control and rationalize diabetologic sanitary planning. METHODS: Fifteen centers in Cataluna participated in a study with a total of 1,430 patients. The centers represented different specialized care levels: 6 endocrinology public health out-patient clinics (EO), 4 county hospitals (CH), 3 university hospitals (UH) and 2 private diabetic units (DU). RESULTS: IDDM: a) the percentage was higher in UH and DU (39 and 37) than in CH (26 p less than 0.01) and EO (11 p less than 0.001); b) the youngest were attended in UH (24 +/- 14 years) and the oldest in the EO (39 +/- 17 years, p less than 0.001), occupying the CH and DU at an intermediate position (34 +/- 16 and 32 +/- 17 years) and different than the other two (p less than 0.05); c) 74% of those attended in UH had an evolution of less than 10 years vs 45-58% of the other levels (p less than 0.005); d) no differences were observed in the overall prevalence of complications; e) 37% of the males between 15 and 64 years of age were smokers; f) intensive insulin therapy is more frequently used (p less than 0.05) in DU and UH (56% and 42%) than in EO and CH (19% and 13%); g) the determination of capillary glycemia is generalized (96%); h) 14% had HbA1 or fructosamine lower than the maximum normal value. NIDDM: a) the age of the patients was somewhat lower in DU (59 +/- 11) and UH (58 +/- 11) than in CH (62 +/- 100 and EO (64 +/- 10 (p less than 0.05); b) globally, the rate of insulinization was 55% and home control of glycemia was 43%; c) 47% are hypertense (half of whom are inadequately controlled) and 55% are dyslipemic; d) between 15 and 64 years of age 39% of the males are smokers; e) 27% had HbA1 or fructosamine lower than the maximum normal value. CONCLUSIONS: a) The quality of medical care to diabetics in the centers analyzed is high; b) there is no "patient-type" for level of health care; c) there seems to be more therapeutic "aggressivity" among the health care workers responsible for diabetics in relation to the glucose vs other risk factors. PMID- 1630207 TI - [General practitioners in Helsingborg: better quality and service]. PMID- 1630206 TI - [An analysis of Spanish biomedical journals by the impact factor]. AB - BACKGROUND: One of the most frequently used parameters for evaluating scientific publications is that of impact factor (IF) published in the Science Citation Index-Journal Citation Reports (SCI-JCR) which evaluates the number of citations a journal receives on behalf of other journals. The present study analyzed the Spanish biomedical journals included in the SCI-JCR by the IF. METHODS: The IF were obtained from the SCI-JCR (1980-89). The journals were evaluated by the IF and the weighted impact factor (WIF) calculated according to WIF = (IF/MIF) x 100 in which MIF = maximum IF of the considered area. RESULTS: Nine Spanish biomedical journals were included in the SCI-JCR, four being basic sciences (Histology and Histopathology, Inmunologia, Methods and Findings in Experimental and Clinical Pharmacology, Revista Espanola de Fisiologia) and five clinical journals (Allergologia et Immunopathologia, Medicina Clinica, Nefrologia, Revista Espanola de las Enfermedades del Aparato Digestivo, Revista Clinica Espanola). Their IF were much lower than the most important journals in each area with the mean (+/- standard deviation) being 0.21 +/- 0.22 (range 0.016-0.627). The mean WIF was 2.88 +/- 4.07 (0.16-12.82). The journals of basic sciences had higher IF and WIF than the clinical journals (p less than 0.05). Only the four journals of basic sciences were included in the SCI. Four journals, those of basic sciences, are preferentially or exclusively published in English and other five are published in Spanish. The differences in IF among these groups were not significant (p = 0.06) while those of WIF were significant (p less than 0.05). The number of Spanish biomedical journals in the SCI-JCR has risen from 1 in 1980 to 9 in 1989 with IF which have evolved variably. CONCLUSIONS: In mind of impact factor, the contribution of Spanish journals is low, with that of biomedical sciences being higher than that of clinical journals. Language and inclusion in the Science Citation Index may explain, at least in part, the low impact factors obtained. PMID- 1630208 TI - [Do not destroy primary health care]. PMID- 1630209 TI - [The right to a smoke-free occupational environment is a reasonable and natural demand]. PMID- 1630210 TI - [Sleeping prone or supine--a question of life or death?]. PMID- 1630211 TI - [Need for a humanistic and dynamic view in psychiatric care]. PMID- 1630212 TI - [Randomization and ethics. Careful planning solves many information problems]. PMID- 1630213 TI - [Prader-Willi syndrome or Angelman syndrome? A question of maternal or paternal chromosome 15]. PMID- 1630214 TI - [Accreditation according to the international norms for better quality assurance in laboratory medicine]. PMID- 1630215 TI - [Triangle revision of 3 emergency departments resulted in significant quality benefits]. PMID- 1630216 TI - [Routine preoperative ECG of younger patients is not justified]. PMID- 1630217 TI - [Depressing development since the 1970's. The incidence of sudden infant death has doubled in all Scandinavian countries]. PMID- 1630218 TI - [Radiofrequency ablation--promising treatment in supraventricular arrhythmia]. PMID- 1630219 TI - [Neurological institutes agree: they suggest new guidelines for handling of suspected vitamin B 12 deficiency]. PMID- 1630220 TI - [Case management--a suitable cooperative function for patients with chronic mental diseases?]. PMID- 1630221 TI - [A British system for classification of health care: "Spri" has studied the Read codes. It should be possible to adapt them for Swedish use]. PMID- 1630222 TI - [Is the duration of forensic psychiatric care dependent on the type of crime or the need of care?]. PMID- 1630223 TI - [The American system is nothing to imitate]. PMID- 1630224 TI - [Clinical research improves national economy--but not with the academics isolated in their ivory towers]. PMID- 1630225 TI - [What is the value of health care evaluations?]. PMID- 1630226 TI - [More extensive psychotherapy education is needed]. PMID- 1630227 TI - [Medical audit: how should the patients with suspected cobalamin deficiency be diagnosed and treated?]. PMID- 1630228 TI - [Prevention against chickenpox in children is unnecessary!]. PMID- 1630229 TI - [The HIV situation in Stockholm 1991. The Swedish model prevents epidemic]. PMID- 1630230 TI - [New diagnostic and therapeutic ways for the diabetic foot]. PMID- 1630231 TI - [New genetic findings radically improve the diagnostic possibilities in fragile X syndrome]. PMID- 1630232 TI - [Unstable DNA fragment can disclose carriers of dystrophia myotonica]. PMID- 1630233 TI - [Disturbed melatonin secretion in patients with thyroid diseases]. PMID- 1630234 TI - [New perspectives on primary hyperparathyroidism]. PMID- 1630235 TI - [The diabetes-nurse--a resource probably saving money and shortening the length of stay]. PMID- 1630236 TI - [Group education in a diabetes school improves the metabolic control]. PMID- 1630237 TI - [Treatment with multiple dosage insulin-pen has not only advantages]. PMID- 1630238 TI - [Private and public ambulatory care centers--comparisons of quality, service and costs]. PMID- 1630239 TI - [Local emergency care centers evaluated--radical changes are possible within the public health care system]. PMID- 1630240 TI - [A critical analysis of imprecise proposals. Are priority listings a tool for prioritization?]. PMID- 1630242 TI - [How much can it cost?]. PMID- 1630241 TI - [At least half a million cases of maternal deaths per year. A chronic disaster with devastating effects on survival of children]. PMID- 1630243 TI - [Child health service as a specialty]. PMID- 1630244 TI - [Malaria and malaria prevention in Sweden]. PMID- 1630245 TI - [What are the limits of the responsibility of the psychotherapy instructor?]. PMID- 1630246 TI - [Acupuncture in asthma? A long-term study should decide]. PMID- 1630247 TI - [Nephropathy induced by a contrast medium--comments on risk factors and prevention]. PMID- 1630248 TI - [Bullying--to bully or being bullied. A questionnaire study in middle schools in Uppsala]. PMID- 1630249 TI - [New discoveries on the etiology of type 1 diabetes--an example of molecular epidemiology]. AB - During the past decade the incidence of type 1 diabetes has been on the increase in Sweden, as it has in many other Western countries. The paper consists in a review of new hypothesis as to the pathogenesis of disease, resulting from findings in intensive molecular, genetic, immunological and epidemiological studies. Reversal of the rising trend in the incidence of type 1 diabetes is dependent upon further detailed elucidation of the molecular biology of the genetic and immunological markers of the disease, and their predictive value in population based studies. The currently identified risk factors, which may be initiators or promoters of diabetes pathogenesis, also need to be further elucidated, for which purpose a molecular epidemiological strategy is recommended, as it has already been found to be a successful approach in studies of type 1 diabetes. PMID- 1630251 TI - [Chronic abscessing skin infection after a splinter in the finger]. PMID- 1630250 TI - [Malaria in Gothenburg 1985-1990. Increasing frequency of malaria necessitates better knowledge of preventive measures]. PMID- 1630252 TI - [Liver transplantation--experiences from the first 100 cases in Gothenburg]. PMID- 1630253 TI - [Despite the shortage of personnel, time, computers and resources: a lot of quality assurance work is done at the Swedish surgical departments today]. PMID- 1630254 TI - [From hygiene to environmental medicine. Need for environmental precautions and improvement of public health requires better education]. PMID- 1630255 TI - [Life expectancy together with good health are health indicators of the public health status]. PMID- 1630256 TI - [Abortions of female fetuses in India--a prenatal sexual discrimination]. PMID- 1630257 TI - [From the golden years to the stormy years--role of the head of the clinical department through 4 decades]. PMID- 1630258 TI - [Family practice and children]. PMID- 1630259 TI - [Transcervical endometrial resection as an alternative to hysterectomy in menorrhagia]. PMID- 1630260 TI - [Who will pay for the competence and readiness of hospitals?]. PMID- 1630261 TI - [It is important for cancer patients to get individual planned written dietary guidelines]. PMID- 1630262 TI - [Is hypertonic dehydration increasing among children with gastroenteritis?]. PMID- 1630263 TI - [Lead poisoning in children is a serious problem in the USA]. PMID- 1630264 TI - [Importance of examination in the choice of the right surgical method of treatment of facial paralysis]. PMID- 1630265 TI - [Fertilization in vitro is successful in nearly half of the treated patients]. PMID- 1630266 TI - [Miraculous luck in an accident]. PMID- 1630267 TI - [Body weight of the Swedish population is increasing]. PMID- 1630268 TI - [Housing adapted to the needs of patients with dementia. Medical competence is necessary during planning]. PMID- 1630269 TI - [Research ethics in practice. Research ethics committees do not guarantee the right to informed consent]. PMID- 1630270 TI - [It can take 10 years between planning and execution of an experiment in space research]. PMID- 1630271 TI - [Pediatricians in primary health care--do general practitioners and pediatricians talk the same language?]. PMID- 1630272 TI - [The thoracic clinic in Umea--a new experimental model for better and cheaper care]. PMID- 1630273 TI - Dietary ether lipid incorporation into tissue plasmalogens of humans and rodents. AB - Chronic feeding of 1-O-octadecyl-sn-glycerol (batyl alcohol) to patients suffering from congenital deficiency in tissue ether glycerolipids showed an increase in the plasmalogens content of their erythrocytes. However, nothing is known about the ether lipid content of other tissues in these patients. Feeding 1 O-heptadecyl-sn-glycerol to young rats showed that this uncommon ether lipid was incorporated to a high extent into the plasmalogens of all tissues except brain. Comparative studies with other precursors, such as 3-O-heptadecyl-sn-glycerol, heptadecanol and heptadecanoic acid, indicated a stereospecific incorporation of the dietary 1-O-alkyl-sn-glycerols into tissue plasmalogens without cleavage of the ether bond. Dietary ether lipids were also shown to be transferred from mothers to suckling rats, but not from pregnant rats to fetuses. The implication of these results to possible dietary ether lipid therapy for patients suffering from peroxisomal disorders is discussed. PMID- 1630274 TI - Characterization of a cytosolic protein in rat liver inhibiting neutral cholesteryl ester hydrolase. AB - Neutral cholesteryl ester hydrolase activity (EC 3.1.1.13) present in microsomes isolated from lactating rat mammary glands was found to be inhibited by a factor (or factors) occurring in the cytosolic fraction of male rat liver. The inhibitor was heat-labile, non-dialyzable, destroyed by proteolysis, and was stable following preparation of an acetone/diethyl ether powder of the cytosolic fraction. The protein also inhibited the activity of hormone-sensitive lipase (HSL) (from bovine adipose tissue) and esterase from Candida cylindracea, but seemed to be more active against the neutral hydrolase found in rat liver microsomes. For the mammary gland microsomal cholesteryl ester hydrolase, the extent of the inhibitory effect was dependent on the concentration of the cytosolic protein, 50% inhibition being achieved by about 100 micrograms of cytosolic protein, and on the method of initiating the enzyme assay. Kinetic analysis indicated that, under circumstances where the reaction was initiated by the addition of substrate, the inhibition was characterized as "uncompetitive." When an inhibitor/substrate complex was allowed to form in the absence of enzyme, an element of "competitive" inhibition was introduced into the reaction. Food withdrawal reduced the activity of the inhibitor in liver by 56%, but activity was fully restored by short-term re-feeding. In contrast, feeding a diet high in fat led to a 34% increase in activity. The present findings suggest that the inhibitory factor(s) may be involved in the regulation of the hydrolysis of cholesteryl esters in the liver and also in other cell types. PMID- 1630275 TI - The inhibition of neutral cholesteryl ester hydrolase by a cytosolic protein factor in female rat liver: the influence of varying hormonal and nutritional conditions on the inhibitory activity. AB - A cytosolic protein, that is inhibitory to neutral cholesteryl ester hydrolase, has been investigated in the livers of female rats using microsomes isolated from the mammary gland of lactating rats as an enzyme source. To facilitate comparisons, inhibitory activity is expressed in terms of the amount (micrograms) of cytosolic protein required to reduce esterase activity by 50% and is compared to the hepatic content of both cholesterol and cholesteryl esters. The experiments revealed a sexual difference in the level of inhibitory activity, with the livers of both suckling and mature male animals containing less of the material than the corresponding females. Alterations in the physiological status of the females, such as pregnancy and lactation, led to a decrease in the activity of the protein. This was reversed by blocking lactation with a combination of an antiserum to rat growth hormone and the anti-prolactin drug, bromocriptine, but not by premature weaning of the animals. Food withdrawal for 24 hr also had the effect of increasing inhibitory activity. In general the cholesteryl ester content of the livers correlated with the level of inhibitory activity. Thus the activity of the cytosolic inhibitor of neutral cholesteryl ester hydrolase responded to changes in both the hormonal and the nutritional status of the female animal. It is suggested that the presence of the greater cholesteryl ester hydrolase inhibitory activity in the female liver may help to explain the lower risk of coronary heart disease in premenopausal females by facilitating increased hepatic storage of the sterol in the form of the ester. PMID- 1630276 TI - Cholestane as a digestibility marker in the absorption of polyunsaturated fatty acid ethyl esters in Atlantic salmon. AB - Salmonid fish require long-chain n-3 fatty acids in their diet. The digestibility of different chemical forms of fish oil fatty acids, fed as triacylglycerols, free fatty acids or ethyl esters, was examined in 300 g farmed Atlantic salmon (Salmo salar) using cholestane as an indicator of fat absorption in lieu of the chromium oxide (Cr2O3) which is commonly used as a marker in digestibility studies. It was established that the two digestibility markers gave similar results. Conveniently, cholestane does not require a separate analysis if fatty acids are to be determined by appropriate gas-liquid chromatography. The long chain polyunsaturated fatty acids were particularly well absorbed, the apparent digestibility being 90-98% when feeding triacylglycerols or free fatty acids. However, the digestibility of monounsaturated fatty acids (75-94%) was lower, and lower still for saturated fatty acids (50-80%). Ethyl esters of fatty acids were significantly less well absorbed (P less than 0.05) than were the corresponding fatty acids in free acid or triacylglycerol form. Irrespective of dietary fat type, only free fatty acids were identified in feces, indicating total hydrolysis of triacylglycerols and ethyl esters. PMID- 1630277 TI - Comparison of the effects of dietary fish oils with different n-3 polyunsaturated fatty acid compositions on plasma and liver lipids in rats. AB - The effects of dietary fish oils with different n-3 polyunsaturated fatty acid compositions on plasma lipid profiles in rats have been studied. Forty-eight male rats, previously maintained on a cholesterol-free diet for 15 days, were fed for 60 days with diets supplemented with 10% fat of either marine hilsa fish (Hilsa ilisa, family clupeidae) or fresh-water chital fish (Notopterus chitala, family notopteridae). The diets had similar levels of total saturated (35-41%), monounsaturated (43-47%) and n-3 polyunsaturated (9-10%) fatty acids. Cholesterol contents of the diets were adjusted to 0.85%; gamma-linolenic acid (3.3%) in chital oil and eicosapentaenoic acid (4.9%) in hilsa oil diets were the major n-3 contributors. The percentage of eicosapentaenoic acid in the chital oil diet was 0.57 times that of the hilsa oil diet, but the eicosapentaenoic (EPA) to arachidonic acid (AA) ratio in the latter (4.08) was 3.2 times that of the former (1.27). Sixty days of hilsa oil diet feeding decreased the levels of cholesterol (53.3 +/- 2.9 to 50.0 +/- 1.1 mg/dL), triacylglycerol (75.7 +/- 3.8 to 64.3 +/- 2.6 mg/dL) and phospholipid (55.8 +/- 1.5 to 51.7 +/- 3.1 mg/dL) in rat plasma. Similar treatment with chital oil diet elevated the plasma cholesterol level (53.3 +/- 2.9 to 62.3 +/- 7.6 mg/dL) while triacylglycerol and phospholipid contents remained unaltered. Both the dietary treatments decreased the levels of linoleic and arachidonic acids in liver but only under the hilsa oil diet did the eicosapentaenoic acid percentage increase markedly (0.8 +/- 0.06% to 5.5 +/- 0.06%) at the expense of arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630278 TI - A colorimetric assay for measuring cell-free and cell-bound cholesterol oxidase. AB - Cholesterol oxidase (cholesterol:oxygen oxidoreductase, EC 1.1.3.6) catalyzes the conversion of sterol delta 5-3 beta-alcohol to the corresponding delta 4-3-ketone with the reduction of oxygen to hydrogen peroxide. Rhodococcus species GK 1, a soil isolated microbe, produces an extracellular and a membrane-bound cholesterol oxidase; the latter is bound to the outer surface of the microbial cell membrane. A simple and sensitive assay is described to measure the two enzyme types; no enzyme extraction is needed for measuring the membrane-bound cholesterol oxidase. In this assay, hydrogen peroxide is reduced by the chromogen 2,2'-azino-bis(3 ethylbenzothiazoline-6-sulfonate) (ABTS) in the presence of horseradish peroxidase, and the increased absorbance is followed continuously at 600 nm (epsilon m = 1.82 x 10(4) M-1.cm-1 at pH 7.0 and 30 degrees C). The standardized assay medium contained 46.9 mM sodium-potassium phosphate buffer pH 7.0, 0.16% Triton X-100, 312.5 microM ABTS, 50 micrograms peroxidase (12.5 units at 25 degrees C), 6.25% isopropanol, 306.3 microM cholesterol or other sterols (kept in solution with isopropanol), and cholesterol oxidase. Oxidation of one molecule of cholesterol by cholesterol oxidase gives one molecule of hydrogen peroxide which reacts with two molecules of ABTS. The method is reproducible and the results correlate well with those obtained by measuring the absorbance of delta 4-cholest 3-one at 240 nm (epsilon m = 1.40 x 10(4) M-1.cm-1 at pH 7.0 and 30 degrees C) and by the method of Allain et al. (Clin. Chem. 20, 470-475, 1974).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630279 TI - The effect of amino acids on choline uptake and phosphatidylcholine biosynthesis in mammalian hearts. AB - The uptake of choline in mammalian hearts in the presence of amino acids was examined. Isolated hamster, guinea pig, rat and rabbit hearts were perfused with labeled choline in the presence and absence of amino acids. Neutral amino acids enhanced choline uptake in the hamster heart, but not in the guinea pig, rat and rabbit hearts. Phosphatidylcholine biosynthesis in these hearts was not affected by the presence of amino acids. Choline uptake in the hamster myocytes was also enhanced by neutral amino acid. The enhancement of choline uptake suggests a direct interaction between the amino acid and the transport of choline into the myocardiac cells. The different responses in choline uptake to neutral amino acids indicate that the regulation of choline uptake in the hearts may be different between mammalian species. PMID- 1630280 TI - Changes in lipid content, fatty acid composition and lipoprotein lipase activity in dry goat omental adipose tissue according to tissue site. AB - Water and lipid contents, fatty acid distribution, and lipoprotein lipase activity were determined in 11 samples taken from the Omentum Majus of five dry Alpine goats. Samples were chosen to standardize sampling sites using geometric guide marks representative of different adipose tissue sites. Sample location explained between 20% and 30% of the total variance in water and lipid contents and in lipoprotein lipase activity, and from 5.5% to 45.4% of the total variance in fatty acid distribution. Increased sample thickness was associated with an increase in lipid content and in saturated fatty acid percentages. Samples taken in proximity of the omentum tissue attached to the rumen and abomasum had the highest content. We furthermore found that the levels of 18:2n-6, 18:1n-7, and of branched chain fatty acids were high close to a pila of the rumen which also corresponded to high lipoprotein lipase activity. Concomitant high levels of 16:1n-7, 17:1n-8, and 18:1n-9 may reflect high levels of delta 9 desaturase activity. PMID- 1630281 TI - Low-density lipoprotein turnover in inbred strains of rabbits hypo- or hyperresponsive to dietary cholesterol. AB - In two inbred strains of rabbit with high or low response of plasma cholesterol to dietary cholesterol, low density lipoprotein (LDL) apolipoprotein (apoLDL) kinetics were determined with the use of a heterologous tracer isolated from a Watanabe heritable hyperlipidemic (WHHL) rabbit. On a diet without added cholesterol, the total clearance of apoLDL (which equals apoLDL production) did not differ significantly between rabbits of both strains. After the feeding of a diet containing 0.1% cholesterol for six weeks, plasma LDL cholesterol, plasma apoLDL and liver cholesterol concentrations rose significantly in the hyperresponsive but not in the hyporesponsive rabbits. Cholesterol feeding depressed the total fractional catabolic rate (FCR) of apoLDL in the hyper- but not in the hyporesponsive rabbits; this was attributed to a decrease of receptor dependent FCR while receptor-independent FCR was similar in the two strains. On the diet containing cholesterol, the receptor-mediated absolute catabolic rate (ACR) of apoLDL did not differ between hyper- and hyporesponsive rabbits but receptor-independent ACR of apoLDL was higher in hyperresponders. It is concluded that the higher plasma apoLDL levels in hyperresponsive rabbits fed the 0.1% cholesterol diet are caused by a higher production of apoLDL and not by a lower flux of apoLDL through the receptor-mediated pathway. PMID- 1630282 TI - Effect of 25-hydroxycholesterol on cholesteryl ester formation in Caco-2 cells. AB - Incubation of Caco-2 cells, a human intestinal cell line, with 25 hydroxycholesterol (25-HOC) marked enhanced cellular cholesteryl ester formation determined by incorporation of [14C]oleic acid into intracellular cholesteryl [14C]oleate. The stimulation by 25-HOC of cholesteryl ester formation was suppressed by staurosporine, a kinase inhibitor, but not by cycloheximide or actinomycin D. The specific activity of microsomal acyl-coenzyme A:cholesterol acyltransferase (ACAT) increased two-fold in cells treated with 10 microM 25-HOC for 5 h. ACAT activity decreased when microsomes were incubated without sodium fluoride, a phosphatase inhibitor, but the decrease in ACAT activity in cells stimulated with 25-HOC was more pronounced. The results suggest that protein phosphorylation may be involved in the stimulation of cholesteryl ester formation by 25-HOC in Caco-2 cells. PMID- 1630283 TI - Comments on essential fatty acid deficient rats fed hydrogenated oil. PMID- 1630284 TI - The forces of bureaucracy. PMID- 1630285 TI - George Boole, mathematical logic, and the modern computer. PMID- 1630286 TI - The World Food Programme at the United Nations. PMID- 1630287 TI - Digital CD-ROMs. PMID- 1630288 TI - The concept of meaning and the mathematical theory of communication. PMID- 1630289 TI - Organizing the clinical data in the medical record. AB - We have developed a method of collecting and arranging clinical data that makes the medical record more useful in patient care and research. The design is based on two principles: that detailed clinical findings should be recorded independently of any diagnostic interpretation, and that time should be integrated as a dimension of the medical record. Analysis of the principal components of the medical record as we have organized it allows identification of clinical entities on the basis of synchronous or sequential features and facilitates precise tracking of symptoms, evaluation of therapeutic effects, comparison of treatments, identification of patients at risk of recurrence, transmission of observations from physician to physician, and analysis and reinterpretation of the observations recorded. PMID- 1630290 TI - A thrombolytic decision tree. AB - We constructed a decision analysis model based on data in the medical literature to estimate the possible outcomes of thrombolytic therapy in patients 50 to 80 years old with possible myocardial infarction. We used the model to test the most likely effects of treatment (determined by averaging the values in reports of large studies) and the worst effects reported so far. The program begins by asking the patient's age, the hours from the onset of pain, and the probability of acute myocardial infarction. It then provides an opportunity to perform sensitivity analyses by changing the values for these variables and for the probability of death in the absence of thrombolytic therapy, as well as for the probability of major stroke and hemorrhage. The counterintuitive findings observed with this program are that the benefits of thrombolytic therapy increase with age and that young patients derive surprisingly little benefit from it. PMID- 1630291 TI - George Boole and the mathematics of logic. 1847. PMID- 1630292 TI - Spreadsheets. PMID- 1630293 TI - Silverplatter literature searches. PMID- 1630294 TI - Pen and display computers. PMID- 1630295 TI - Adherence and colonization mechanisms of enteropathogenic and enterohemorrhagic Escherichia coli. PMID- 1630296 TI - Purification and characterization of a Salmonella typhimurium agglutinin from gut mucus secretions. AB - One of the earliest events in Salmonella typhimurium pathogenesis seems to be the interaction of the bacterium with the mucus of the gut. After exposing S. typhimurium to guinea-pig colon, we were able to demonstrate by electron microscopy that S. typhimurium bacteria were trapped on, or in, the mucus layer. Specific components isolated from crude mucus secretions were found to aggregate the bacteria. The degree of bacterial aggregation was dependent on the protein concentration of the crude mucus and on time. Aggregation of S. typhimurium could be abolished by sugars: L-fucose exhibited the strongest inhibition, followed by D-glucose, D-galactose and D-mannose. Lectins were also capable of inhibiting aggregation, the lectin of Ulex europaeus (UEA I), specific for L-fucose, was found to be a stronger inhibitor of bacterial aggregation than Con A. The agglutinin for S. typhimurium isolated from guinea-pig colonic crude mucus preparation was characterized as a 15 kDa glycoprotein. An affinity-purified anti 15 kD antibody inhibited, dose-dependently, the aggregation of S. typhimurium by crude mucus material. PMID- 1630297 TI - Immunosuppression induced by attenuated Salmonella: effect of LPS responsiveness on development of suppression. AB - A live, avirulent strain of Salmonella typhimurium, SL3235, was previously shown to afford protection against virulent Salmonella challenge in three mouse strains of the C3H lineage, C3H/HeJ, C3HeB/FeJ, and C3H/HeNCrlBR, which differ in their innate susceptibility to Salmonella infection, as well as in their responsiveness to lipopolysaccharide (LPS). Concurrent with protection, however, SL3235 was found to induce greater than 90% reduction in proliferative responses of splenocytes from immunized mice to a panel of B and T cell mitogens. Suppression appeared to be independent of susceptibility to Salmonella infection, since the mitogenic responses of hypersusceptible C3H/HeJ and C3HeB/FeJ, as well as resistant C3H/HeNCrlBR mice, were suppressed. The suppressor cell population in immunized C3HeB/FeJ mice was recently shown to be of monocytic lineage. Using transwell plates, co-culture studies indicated that suppression was mediated by soluble factors. In the present study, the effect of LPS responsiveness on susceptibility to SL3235-induced suppression was evaluated in C3H mice by studying their ability to mount plaque-forming cell (PFC) responses to sheep red blood cells (SRBC) and in vivo antibody responses to tetanus toxoid. Comparison of PFC responses as a function of SL3235 dose in C3HeB/FeJ and C3H/HeJ mice, revealed that the latter strain was markedly more resistant to the development of suppression, as evidenced by the significantly higher (10-35-fold) SL3235 doses needed to achieve comparable suppression to those seen in C3HeB/FeJ mice. In contrast to C3HeB/FeJ mice, suppression in C3H/HeJ mice required direct cell-cell contact. In both mouse strains, suppression was alleviated by pre-treatment of immune splenocytes with either mitomycin C or x-irradiation, indicating that actively proliferating cells are required for suppressor function. Resistance of C3H/HeJ mice to SL3235-induced suppression was not due to a lesser bacterial load in vivo, since a higher number of SL3235 organisms were seen in C3H/HeJ spleens compared to C3HeB/FeJ mice. Rather, resistance of C3H/HeJ mice correlated with their reduced ability to recruit macrophages and other inflammatory cells into the spleen, as evidenced by the significantly smaller degree of splenomegaly induced in these mice following immunization with SL3235. PMID- 1630298 TI - Examination by site-directed mutagenesis of the amino acid residues of the thermostable direct hemolysin of Vibrio parahaemolyticus required for its hemolytic activity. AB - The amino acid sequences of eight variants of thermostable direct hemolysin (TDH) and a TDH-related hemolysin, deduced from nucleotide sequences, were compared. Fourteen amino acid residues, mainly within conserved regions, were chosen to prepare mutant TDHs with one or two amino-acid replacements by site-directed mutagenesis. Of the 25 mutant TDHs prepared, those with replacements of Trp65 (Trp65-His65, Trp65-Tyr65, Trp65-Leu65) or Leu66 (Leu66-Ser66) showed very significant reduction (more than 150-fold) of hemolytic activity. Several other mutant TDHs with replacements at Lys45, Arg46 and Gly90 showed weaker hemolytic activity than the wild-type TDH, but extents of reduction in hemolytic activity were much less than for mutant TDHs with replacements at Trp65 and Leu66. These results indicate that Trp65 and Leu66 are very important for the hemolytic activity of TDH. PMID- 1630299 TI - Evidence for three different fibrinogen-binding proteins with unique properties from Staphylococcus aureus strain Newman. AB - Binding of extracellular components of Staphylococcus aureus strain Newman to fibrinogen and prothrombin was investigated. Affinity-purified material from fibrinogen- and prothrombin-Sepharose was analysed on immunoblots, and two proteins with coagulase activity were identified. The two coagulases were produced in a sequential manner during staphylococcal growth. An 87 kDa fibrinogen-binding coagulase was produced mainly during the exponential growth phase and was replaced by a 60 kDa fibrinogen- and prothrombin-binding coagulase which was produced mainly during the post-exponential growth phase. In addition, a 19 kDa fibrinogen-binding protein was constitutively produced. Analyses of immunogenic properties and NH2-terminal sequences suggested that the 19, 60 and 87 kDa fibrinogen-binding proteins are not closely related. The NH2-terminal sequence of the 87 kDa protein is identical to a previously described coagulase from Staphylococcus aureus strain 8325-4. The 19 kDa fibrinogen-binding protein, which spontaneously aggregates into dimers and larger molecular weight complexes, had a unique NH2-terminal sequence. PMID- 1630300 TI - Impaired resistance to infection does not increase the virulence of Salmonella htrA live vaccines for mice. AB - We have described a new class of live attenuated salmonella vaccines harbouring lesions in htrA, a stress protein gene previously. The virulence and invasiveness of Salmonella htrA mutants was investigated in three models of increased susceptibility to Salmonella infection. These included BALB/c mice, either given sublethal whole body irradiation (350 R) or administered rabbit anti-TNF alpha antiserum, and (CBA/NfemaleXBALB/cmale)F1 male mice which express the xid sex linked B cell defect of CBA/N mice and are more susceptible to salmonellae than female littermates. Salmonella typhimurium htrA mutants derived from virulent strains, C5046 (C5 htrA::TnphoA) and BRD726 (SL1344 delta htrA) were not more invasive in immunosuppressed mice than in normal controls in the three mouse models of defective immunity. The results indicate that susceptibility to S. typhimurium htrA vaccines derived from virulent parents is not enhanced by conditions of impaired resistance to infection. PMID- 1630301 TI - The evolution of the mitochondrial D-loop region and the origin of modern man. AB - The origin of modern man is a highly debated issue that has recently been tackled by using mitochondrial DNA sequences. The limited genetic variability of human mtDNA has been explained in terms of a recent common genetic ancestry, thus implying that all modern-population mtDNAs originated from a single woman who lived in Africa less than 0.2 Mya. This divergence time is based on both the estimation of the rate of mtDNA change and its calibration date. Because different estimates of the rate of mtDNA evolution can completely change the scenario of the origin of modern man, we have reanalyzed the available mitochondrial sequence data by using an improved version of the statistical model, the "Markov clock," devised in our laboratory. Our analysis supports the African origin of modern man, but we found that the ancestral female from which all extant human mtDNAs originated lived in a time span of 0.3-0.8 Mya. Pushing back the date of the deepest root of the human implies that the earliest divergence would have been in the Homo erectus population. PMID- 1630303 TI - Phylogenetic reconstruction of the Drosophila obscura group, on the basis of mitochondrial DNA. AB - We have constructed restriction-site maps of the mtDNAs in 13 species and one subspecies of the Drosophila obscura group. The traditional division of this group into two subgroups (affinis and obscura) does not correspond to the phylogeny of the group, which shows two well-defined clusters (the Nearctic affinis and pseudoobscura subgroups) plus a very heterogeneous set of anciently diverged species (the Palearctic obscura subgroup). The mtDNA of Drosophila exhibits a tendency to evolve toward high A+T values. This leads to a "saturation" effect that (1) begets an apparent decrease in the rate of evolution as the time since the divergence of taxa increases and (2) reduces the value that mtDNA restriction analysis has for the phylogenetic reconstruction of Drosophila species that are not closely related. PMID- 1630302 TI - Maintenance of DQB1 polymorphisms in primates. AB - To understand the evolution of the class II major histocompatibility complex (MHC) DQB1 locus in primates, the second exons of seven DQB1 alleles from five non-human primate species were amplified by polymerase chain reaction. Comparisons of these and other primate sequences show that no between-species diversity is greater than within-species diversity, suggesting maintenance of DQB1 alleles through the history of Old-World primates. There is a preponderance of nonsynonymous nucleotide substitutions at antigen-binding-site codons; this pattern is in marked contrast to what is seen at the closely related, presumably nonfunctional DQB2 gene. The results support the hypothesis that DQB1 polymorphism is maintained by overdominant selection relating to antigen presentation. PMID- 1630304 TI - Phylogeny of five fungus-like protoctistan Phytophthora species, inferred from the internal transcribed spacers of ribosomal DNA. AB - Ribosomal DNA variation was used to study evolutionary relationships among five fungal-like protoctistan Phytophthora species. On the basis of morphological and ecological characteristics, four of these species--P. palmivora, P. megakarya, P. capsici, and P. citrophthora--were once thought to be related. Variation within a species was extensively studied in a fifth, outgroup species--P. cinnamomi- known, on the basis of ecological, isozyme, and mitochondrial DNA studies, to be variable. Internal transcribed spacer regions (ITS I, between the 18S and 5.8S rDNAs; and ITS II, between the 5.8S and 25S rDNAs) from 27 isolates of these five species were analyzed by polymerase chain reaction amplification and direct sequencing. Intraspecific variability was undetected or low. Interspecific nucleotide difference was 0.3%-14.6%, and comparisons of variable regions permitted the evaluation of phylogenetic relationships among species. Both neighbor-joining and parsimony analysis of ITS variability support a close relationship between cacao isolates of P. capsici and P. citrophthora and a common lineage for P. palmivora and P. megakarya. Large distance values were estimated between P. cinnamomi and the other species. Inferred relationships based on ITS variability were compared with those based on other characters. The catalog of sequences provides the information necessary to design taxon-specific probes potentially useful in taxonomic, ecological, and population-level studies. PMID- 1630305 TI - Molecular population genetics of Escherichia coli: DNA sequence diversity at the celC, crr, and gutB loci of natural isolates. AB - The DNA sequences of three genes--celC, crr, and gutB--have been determined for each of 11 or 12 natural isolates of Escherichia coli from the ECOR collection. These genes encode the phosphoenolpyruvate-dependent phosphotransferase-system enzyme III proteins specific for beta-glucoside sugars (celC), glucose (crr), and glucitol (gutB), respectively. There is little evidence of recombination at or among these loci; among these strains, relationships inferred from each gene are largely consistent with each other and with the relationship inferred from multilocus enzyme electrophoresis. DNA sequence diversity is similar for all three genes, particularly when silent (synonymous) sites only are considered. This is surprising because there is much stronger codon usage bias at crr than at celC or gutB. The extent of divergence in the protein sequences encoded by these three genes varies considerably. The constitutively expressed glucose-specific enzyme is completely conserved. It is surprising that the inducible glucitol specific enzyme, which is functional, is more variable than the cellobiose specific enzyme, which is cryptic; the latter might be expected to be under less (if any) purifying selection. PMID- 1630306 TI - Estimation of the number of nucleotide substitutions when there are strong transition-transversion and G+C-content biases. AB - A simple mathematical method is developed to estimate the number of nucleotide substitutions per site between two DNA sequences, by extending Kimura's (1980) two-parameter method to the case where a G+C-content bias exists. This method will be useful when there are strong transition-transversion and G+C-content biases, as in the case of Drosophila mitochondrial DNA. PMID- 1630307 TI - Nucleotide sequence, function, activation, and evolution of the cryptic asc operon of Escherichia coli K12. AB - The cryptic asc (previous called "SAC") operon of Escherichia coli K12 has been completely sequenced. It encodes a repressor (ascG); a PTS enzyme IIasc for the transport of arbutin, salicin, and cellobiose (ascF); and a phospho-beta glucosidase that hydrolyzes the sugars which are phosphorylated during transport (ascB). ascG and ascFB are transcribed from divergent promoters. The cryptic operon is activated by the insertion of IS186 into the ascG (repressor) gene. The ascFB genes are paralogous to the cryptic bglFB genes, and ascG is paralogous to galR. The duplications that gave rise to these paralogous genes are estimated to have occurred approximately 320 Mya, a time that predates the divergence of E. coli and Salmonella typhimurium. PMID- 1630308 TI - Similarity, in molecular structure and function, between the plant toxin purothionin and the mammalian pore-forming proteins. AB - Many proteins containing domains of a cysteine-rich repeated motif, such as epidermal growth factor (EGF), have been reported. Here we report strong similarity between the amino acid sequence of a plant toxin--i.e., purothionin and its homologues--and with those of a domain found in mammalian pore-forming cytoplasmic proteins: components of complement and perforin of cytotoxic T lymphocytes or natural killer-like cytotoxic cells. These similar sequences were found to be identical to the so-called EGF-like cysteine-rich repeated motif itself. Electron-microscopic observations indicated that, like complement and perforin, purothionin forms pores in the cytoplasmic membrane of target cells, resulting in their death within a few hours. On the basis of these sequence comparisons and physiological functions, we propose a scheme for the evolution of proteins containing modules of the cysteine-rich repeat motif. PMID- 1630309 TI - Estimation of heterozygosity for single-probe multilocus DNA fingerprints. AB - In spite of the increasing application of DNA fingerprinting to natural populations and to the genetic identification of humans, explicit methods for estimation of basic population genetic parameters from DNA fingerprinting data have not been developed. Contributing to this omission is the inability to determine, for multilocus fingerprinting probes, relatively important genetic information, such as the number of loci, the number of alleles, and the distribution of these alleles into specific loci. One of the most useful genetic parameters that could be derived from such data would be the average heterozygosity, which has traditionally been employed to measure the level of genetic variation within populations and to compare genetic variation among different loci. We derive here explicit formulas for both the estimation of average heterozygosity at multiple hypervariable loci and a maximum value for this estimate. These estimates are based upon the DNA restriction-pattern matrices that are typical for fingerprinting studies of humans and natural populations. For several empirical data sets from our laboratory, estimates of average and maximal heterozygosity are shown to be relatively close to each other. Furthermore, variances of these statistics based on simulation studies are relatively small. These observations, as well as consideration of the effect of missing alleles and alternate numbers of loci, suggest that the average heterozygosity can be accurately estimated using phenotypic DNA fingerprint patterns, because this parameter is relatively insensitive to the lack of certain genetic information. PMID- 1630310 TI - Sequencing errors and molecular evolutionary analysis. AB - Heuristic approaches were used to quantify the influence that sequencing errors have on estimates of nucleotide diversity, substitution rate, and the construction of genealogies. Error rates of less than 1 nucleotide/kb probably have little affect on conclusions about the evolutionary history of highly polymorphic organisms such as Drosophila and Escherichia coli, but organisms with very low nucleotide diversity, such as humans, require greater sequencing accuracy. A scan of GenBank for corrections of previous errors reveals that sequencing errors are highly nonrandom. PMID- 1630311 TI - Sample size for a phylogenetic inference. AB - The objective of this work is to describe sample-size calculations for the inference of a nonzero central branch length in an unrooted four-species phylogeny. Attention is restricted to independent binary characters, such as might be obtained from an alignment of the purine-pyrimidine sequences of a nucleic acid molecule. A statistical test based on a multinomial model for character-state configurations is described. The importance of including invariable sites in models for sequence change is demonstrated, and their effect on sample size is quantified. The methods are applied to a four-species alignment of small-subunit rRNA sequences derived from two archaebacteria, a eubacteria and a eukaryote. We conclude that the information in these sequences is not sufficient to resolve the branching order of this tree. Estimates of the number of aligned nucleotide positions required to provide a reasonably powerful test are given. PMID- 1630312 TI - Early events in yeast mitochondrial protein targeting. AB - Protein import into mitochondria involves a number of complex steps occurring in the cytosol, on the mitochondrial surface, and inside the organelle. Once an initial interaction between mitochondrial proteins and their specific receptors occurs, the proteins are transported into the organelle in a series of reactions involving (in the case of a protein to be translocated into the mitochondrial matrix) the mitochondrial membrane potential, ATP hydrolysis and an undetermined number of membrane components. Inside the organelle, mitochondrial proteins are processed and sorted to their final intramitochondrial destinations. The earliest steps in the import process take place in the cytosol and include the synthesis of the mitochondrial proteins themselves, their interaction with cytosolic factors, and perhaps the establishment of cotranslational import complexes on the mitochondrial surface. These early events are important because it is during this phase that the system as a whole is most sensitive to cytosolic conditions that may exert control over the entire import process. PMID- 1630313 TI - Human neutrophil response to recombinant neisserial Opa proteins. AB - Interactions of human neutrophils with recombinant Escherichia coli expressing gonococcal outer membrane Opa proteins were examined using chemiluminescent and biological assays. Seven opa loci from Neisseria gonorrhoeae MS11 4.8 were expressed as beta-lactamase-Opa fusion proteins that contained all but the mature N-terminal amino acid of the full-length Opa protein fused to three N-terminal amino acids derived from the mature beta-lactamase. The Opa fusion proteins were exported and assembled in the outer membrane of E. coli in a manner similar to that of Opa in N. gonorrhoeae, as evaluated by antibody binding and in situ proteolytic cleavage. All fusion proteins exhibited the characteristic heat modifiable migration in SDS-polyacrylamide gel electrophoresis that typifies Opa proteins of neisseriae. Opa fusion proteins conferred on E. coli the ability to stimulate a chemiluminescent response from human neutrophils in the absence of antibody or complement. The nature of the response in terms of chemiluminescence, phagocytosis, and killing was in all cases analogous to that seen using N. gonorrhoeae expressing the equivalent Opa protein. Neither E. coli nor gonococci expressing OpaA elicited a response from neutrophils. Use of E. coli expressing Opa fusions should be useful in defining their biological activities and pathogenic roles. PMID- 1630314 TI - Characterization of transformation-deficient mutants of Acinetobacter calcoaceticus. AB - Three Acinetobacter calcoaceticus transformation-deficient mutants, obtained by insertional mutagenesis with the nptll gene, have been characterized physiologically. One mutant (AAC211) was found to be completely transformation deficient, while two others, AAC213 and AAC214, were severely impaired in transformation efficiency (100-1000 times lower than the wild type). The latter applied to both chromosomal as well as plasmid DNA. Analysis of the chromosomal DNA fragments flanking the nptll gene in the mutants showed that mutants AAC213 and AAC214 had an insertion of the nptll gene in the same chromosomal region, but that they were the result of two independent mutational events, whereas the insertion in mutant AAC211 was at a different position. None of the three mutants showed phenotypic or genotypic characteristics typical of a RecA-deficient strain. PMID- 1630315 TI - Molecular analysis of the lac operon encoding the binding-protein-dependent lactose transport system and beta-galactosidase in Agrobacterium radiobacter. AB - The genes coding for the binding-protein-dependent lactose transport system and beta-galactosidase in Agrobacterium radiobacter strain AR50 were cloned and partially sequenced. A novel lac operon was identified which contains genes coding for a lactose-binding protein (lacE), two integral membrane proteins (lacF and lacG), an ATP-binding protein (lacK) and beta-galactosidase (lacZ). The operon is transcribed in the order lacEFGZK. The operon is controlled by an upstream regulatory region containing putative -35 and -10 promoter sites, an operator site, a CRP-binding site probably mediating catabolite repression by glucose and galactose, and a regulatory gene (lacl) encoding a repressor protein which mediates induction by lactose and other galactosides in wild-type A. radiobacter (but not in strain AR50, thus allowing constitutive expression of the lac operon). The derived amino acid sequences of the gene products indicate marked similarities with other binding-protein-dependent transport systems in bacteria. PMID- 1630316 TI - Clarification of the structural and functional features of the osmoregulated kdp operon of Escherichia coli. AB - Expression of the Escherichia coli kdpABC operon, which is responsible for a high affinity potassium-uptake system, is regulated in response to a change in the medium osmolarity. In this study, we clarified the structure and function of the kdpABC promoter including its regulatory sequence at the molecular level. The canonical -35 and -10 regions determined for the promoter were not fully functional, i.e. in addition to them, a cis-acting sequence located upstream of the -35 region was essential for full activation of the promoter. This upstream sequence was demonstrated to be the target site for the trans-acting activator, KdpE. PMID- 1630317 TI - Phosphotransfer signal transduction between two regulatory factors involved in the osmoregulated kdp operon in Escherichia coli. AB - The proteins KdpD and KdpE are regulatory factors critically involved in the osmotic regulation of the kdpABC operon that is responsible for a high-affinity transport system in Escherichia coli. In this study, we obtained biochemical evidence supporting the view that the KdpD protein is a sensory protein kinase that exhibits autophosphorylation and KdpE-phosphotransfer characteristics. During the course of such studies we established a procedure for purifying the KdpE protein in large quantities. We also developed a procedure for preparing cytoplasmic membrane enriched with the KdpD protein that exhibits in vitro ability with regard to phosphorylation of KdpE protein. PMID- 1630318 TI - Interaction of the regulatory protein NicR1 with the promoter region of the pAO1 encoded 6-hydroxy-D-nicotine oxidase gene of Arthrobacter oxidans. AB - The D,L-nicotine catabolism of the Gram-positive soil bacterium Arthrobacter oxidans is linked to the presence within the cells of the 160 kb catabolic plasmid pAO1. pAO1-cured cells lost the catabolic enzymes and reintroduction of pAO1 by electroporation into cured cells reestablished the nic+ phenotype. DNA band shift assays with extracts from cured and pAO1+ cells suggested that pAO1 encodes the regulatory protein NicR1. Footprint analysis revealed that two homologous palindromes (IR1 and IR2), present in the 5'-regulatory region of the 6-HDNO gene, were protected from DNase I digestion. Binding of NicR1 to the palindromes is symmetrical, co-operative, and stronger to IR1 containing the 6 HDNO gene promoter than to IR2. Site-directed mutagenesis revealed that steric constraints and sequence requirements for NicR1-binding are located exclusively in the palindromic sequences. Deletions and insertions in the interpalindromic region and in the 6-HDNO promoter -10 sequence had no effect on the binding characteristics of NicR1 to the 6-HDNO regulatory region. Acting as a repressor, NicR1 prevents binding of the E. coli RNA-polymerase to the consensus sigma 70 promoter in vitro. However, the interaction of NicR1 with the 6-HDNO promoter region in extracts of nicotine-induced cells from various growth stages did not differ from that observed with extracts of nicotine-uninduced cells. PMID- 1630319 TI - Occurrence of a Photosystem II polypeptide in non-photosynthetic membranes of cyanobacteria. AB - Cytoplasmic and thylakoid membranes have been purified from the cyanobacteria Anacystis nidulans R2 and Phormidium laminosum by sucrose density gradient centrifugation. Probing of Western blots of proteins from these purified membrane fractions with antibodies directed against the 33 kDa polypeptide of Photosystem II from pea indicates that this protein is present in both the thylakoid and cytoplasmic membranes, rather than just the thylakoid membranes. This has been confirmed by immunogold labelling of cells. Oxygen evolution assays have been used to show that the 33 kDa polypeptide is not assembled into a functional Photosystem II complex in the cytoplasmic membranes. This may be due to the absence of other Photosystem II components. PMID- 1630320 TI - Expression of the Escherichia coli dam gene. AB - The Escherichia coli dam gene and upstream sequences were cloned from the Kohara phage 4D4. Five promoters were found to contribute to dam gene transcription. P1 and P2 (the major promoter) were situated approximately 3.5 kb upstream of the structural gene, P3 was within the aroB gene, P4 was within the urf74.3 gene, and P5 was in the urf74.3-dam intergenic region. The nucleotide sequence of 2280 bp of DNA containing P1 and P2 was determined and shown to have the potential to encode a protein of approximately 16 kDa between P1, P2 and the aroB gene. This 16 kDa open reading frame has been identified as aroK, the gene for shikimic acid kinase I. Thus the dam gene is part of an operon containing aroK, aroB, urf74.3, and dam. The transcriptional start points of the promoters were determined. A comparison of their nucleotide sequences suggested that P1-P4 were all recognized by the sigma 70 subunit of the RNA polymerase. PMID- 1630321 TI - NtcA, a global nitrogen regulator from the cyanobacterium Synechococcus that belongs to the Crp family of bacterial regulators. AB - The gene ntcA is required for full expression of proteins subject to ammonium repression in the cyanobacterium Synechococcus. A 3.1 kb DNA fragment able to complement an ntcA mutant was digested with exonuclease III, and deleted fragments of different size were tested for complementation of that mutant, allowing the localization of its mutation within a BamHI-HindIII genomic fragment of c. 0.4 kb. Insertion of a chloramphenicol-resistance-encoding gene cassette into both the BamHI and the HindIII sites of wild-type Synechococcus resulted in a pleiotropic, nitrogen-assimilation-minus phenotype, corroborating the presence of the ntcA gene in that genomic region. Sequencing of DNA in this region showed the presence of an open reading frame that included both the BamHI and the HindIII sites. The ntcA gene product, NtcA, is a protein of 24817 Da which belongs to a family of bacterial transcriptional activators that, among others, includes Crp and Fnr from Escherichia coli. Of special biological significance, it appears, is the presence of a conserved helix-turn-helix motif in the sequence close to the C-terminal end of all the proteins in the family. The gene ntcA is proposed to encode a transcriptional activator of genes subject to nitrogen control in Synechococcus. PMID- 1630322 TI - Lasers and their use in dentistry. PMID- 1630323 TI - Clients/patients with a principal diagnosis of affective disorder served in the inpatient, outpatient, and partial care programs of specialty mental health organizations, United States, 1986. AB - Of the 1.7 million persons under care on April 1, 1986 in the psychiatric inpatient, outpatient, and partial care programs of specialty mental health organizations nationwide, approximately 365,500 persons, or 22 percent, had a principal diagnosis of affective disorder. The vast majority of these persons, 84 percent, were under care in outpatient programs; 10 percent, in inpatient programs; and 6 percent, in partial care programs. Approximately 833,000, or 21 percent, of the 3.9 million persons admitted during 1986 to these same psychiatric programs had a diagnosis of affective disorder. Fifty-nine percent of persons with affective disorders were admitted to inpatient programs; 37 percent, to outpatient programs; and 4 percent, to partial care programs. Overall, most persons with affective disorders admitted to and under care in each of the three program types were female, white, and between the ages of 25 and 64. Most persons admitted to and under care in inpatient and partial care programs had a history of prior inpatient mental health care, while most persons in outpatient programs had never been treated in an inpatient psychiatric care setting. The principal source of payment used by persons with affective disorders varied by type of program setting. Blue Cross or other commercial insurance was the most common source of payment used by persons within inpatient programs, personal resources were used most often by persons under care in outpatient programs, and some type of public funds was used most often within partial care programs. Most persons with affective disorders were referred to inpatient and outpatient programs by family or friends, or were self-referrals. Most persons in partial care programs with affective disorders were referred to the program by an inpatient, outpatient, or another partial care mental health service. Services received by persons with affective disorders also varied by program setting. In general, drug and individual therapy were the leading types of treatment provided in inpatient programs. Individual therapy was the leading type of treatment provided, followed by drug therapy, in outpatient programs. Within partial care programs, no single type of treatment predominated. PMID- 1630324 TI - Patient care episodes in mental health organizations, United States: selected years from 1955 to 1988. AB - The 4,930 mental health organizations providing mental health services in the United States during 1988 (excluding the Territories) generated just over 8.3 million patient care episodes (table 1). However, in order to compare 1988 data with those for other years dating back to 1955, outpatient and partial care programs administered by the Department of Veterans Affairs (formerly the Veterans Administration) (VA) need to be omitted (table 2). Thus the 7.8 million patient care episodes in 1988 (exclusive of VA outpatient and partial care programs) represented a more than four-fold increase over the 1.7 million patient care episodes in mental health organizations observed more than three decades earlier in 1955. The major shifts in patient care episodes over the period from 1955 to 1988 have been from inpatient to ambulatory care services in mental health organizations, and from State and county mental hospitals to community based mental health organizations. For example, in 1955, 77 percent of all patient care episodes were inpatient episodes, and the remaining 23 percent were outpatient episodes. By 1988, inpatient episodes constituted only 28 percent of the total, while 66 percent were outpatient episodes, and 6 percent were partial care episodes (table 2 and figure 1). However, the relative distribution of inpatient, outpatient, and partial care episodes has been relatively stable since 1975. From 1955 to 1988, the primary locus of inpatient care shifted from State and county mental hospitals to non-Federal general hospitals. Also, by 1988, the locus of over one-half of the outpatient care episodes and almost two-thirds of the partial care episodes was in multiservice mental health organizations. PMID- 1630325 TI - Medical education and political reform. PMID- 1630326 TI - Sustaining and rewarding clinical teaching. AB - High standards of clinical teaching are essential in the training of medical students but greater prominence needs to be given to its importance. Strategies are described by which one medical school has raised the awareness of clinical teaching and supported those who deliver it. PMID- 1630327 TI - The role of expatriate advisers: effective teaching in Indonesian medical education. AB - The expatriate advisor or 'expert' working in Indonesian medical education will require a complex range of personal and professional qualities if he or she is to be effective. Personal qualities refer particularly to the nature of the relationships that are established. Professional qualities include expertise in the discipline as well as expertise in teaching and education more generally. None of the qualities identified in the study is simple or unidimensional. The qualities are complex and are also likely to vary among educators according to their own level of education and cross-cultural experience. PMID- 1630328 TI - Retention of interviewing skills learned by first-year medical students: a longitudinal study. AB - A pilot interviewing course was offered as an elective to first-year medical students in the spring of 1985. A quasi-experimental pre-test/post-test control group demonstrated that students who took the course exhibited a significant increase in interviewing skills. Subjects, 15 in the experimental group and 11 in the control group, were assessed in each of the following 3 years. Data consisted of five 10-minute videotaped interviews with real or stimulated patients for each subject and subject's responses on a degree of confidence, familiarity and anxiety scale. Interviews were rated on 43 behaviours by two independent coders with a 90% simple agreement. The experimental group did not maintain their scores on interviewing skills and both groups showed a significant decline in nine skills comprising empathy. The only significant difference between the groups in fourth year was on the degree of confidence experienced. While interviewing skills can be learned they decline in the clinical years as students learn medical problem-solving. If medical students are to graduate with their original empathy intact, a follow-up course in fourth year is indicated. PMID- 1630329 TI - Teaching clinical skills to new medical students: the Oman experience. AB - The College of Medicine at the Sultan Qaboos University (SQU) in Oman took up the challenge of moving away from a didactic emphasis in the teaching of family and community health by actively involving students in health care, requiring some clinical skills, as early as possible. This paper describes the experience of the Department of Family and Community Health at SQU of the feasibility of training first-year medical students in the measurement of blood pressure within a few days. Our experience showed that proper training before starting field-work can teach clinical skills to students who have had no prior exposure to medical subjects. There was a strong correlation between the measurements of blood pressure of 638 individuals by the students and the supervisors. This experience at SQU has encouraged us to implement the idea of family- and community-based clinical exposure for every class. Teaching of clinical skills is feasible in the field for new entrants, provided there is adequate orientation beforehand and skilled supervision of the students in small groups. PMID- 1630330 TI - Attitudes of medical students to old people: a cross-national comparative study. AB - Medical students' attitudes to the elderly were compared at the start and finish of a 5-week clinical attachment in health care of the elderly at the Christchurch School of Medicine. The study investigated students in their first clinical year (fourth year of their medical course) over five terms using a questionnaire employing a Rosencranz-McNevin semantic differential scale to measure general attitudes to old age and a Likert scale to measure attitudes to medical care. A question was also asked about career preferences. There was significant improvement in attitudes measured by both scales (Rosencranz-McNevin P less than 0.001, Likert P less than 0.001). Students also showed an increase in interest in health care of the elderly as a career choice. When compared with two cohorts of students from Nottingham Medical School, attitudes were significantly better in the Christchurch group at the commencement of the run. Students at both schools showed an improvement in knowledge but this was more marked for Christchurch students. PMID- 1630331 TI - Teaching bioethics to medical students: the Newcastle experience. AB - Over the past two decades in the USA, bioethics has become an accepted component of medical education, whereas in Australia, 10 years or even less would encompass the history of most existing programmes. Given the legendary conservatism of medical schools in Australia and the intractability of the medical curriculum, this is still a remarkable achievement. But does the teaching of bioethics change the thinking and/or decision-making behaviour of medical students or practitioners exposed to such courses? Those involved know only too well how difficult such courses are to design and evaluate since the connection between ethics education and practice is not known and may never be demonstrated to the satisfaction of critics. Critics not only seek answers to the questions of whether the teaching of bioethics makes a difference, which is a fair question, but they also seek answers to the question of whether bioethics should be taught in medical schools. Can bioethics be taught? Whose bioethics is being taught? What does the trained bioethicist contribute? Some of these questions arise from misunderstanding and some reflect the still too dominant view in medical schools which divides disciplines into those which provide 'practical skills', and those which contribute only theoretical and therefore peripheral knowledge. The authors will address these questions in the light of their experience at Newcastle, Australia, where the Faculty of Medicine has been teaching bioethics for over a decade. PMID- 1630332 TI - Multiple-choice testing in anatomy. AB - An analysis of 596 multiple-choice questions (MCQs) on human anatomy given at three First Professional Examinations for medical students is reported. The MCQ paper at each examination was 200 items long and consisted of three item-types: A, K and T/F. Each A-type item comprised a stem and five options, only one of the latter being the correct or best answer. Items of the K-type consisted of a stem and four responses, any number of which may be correct. The T/F items were of the three-response kind, the available options being 'true', 'false' and 'don't know'. Test reliability was computed by internal analysis, using the Kuder Richardson 20 formula. Measures of concurrent validity were obtained by correlating the scores in the MCQ papers with the overall outcome of the First Professional Examination. Indices of item facility, discrimination and abstention were calculated. The effects of item-type and the availability of the 'don't know' option on examinee performance were also determined. Reliability (alpha) and concurrent validity (Pearson r) coefficients in the ranges of 0.71-0.85 and 0.80-0.93 (P less than 0.05) respectively were recorded. Regression analysis revealed the MCQ papers to be less sensitive predictors of the aggregate performance than the essay papers. The proportion of highly discriminatory and excessively difficult items was highest for the K-type. When the same K-type questions were re-exhibited in the indeterminate format, the examinees performed significantly better. Higher scores were also recorded when candidates were required to respond to all the questions than when they were offered the 'don't know' option and the percentage gain was higher for the low-scoring examinees. The appropriateness of multiple-choice testing as a tool for assessing student achievement in human anatomy is discussed. PMID- 1630333 TI - The consistency of students' self-assessments in short-essay subject matter examinations. AB - This longitudinal study compares the accuracy of self-assessments of 22 students across four examinations during their first 2 years of medical school. The four examinations used a similar short-essay format and covered many of the same basic science disciplines at similar levels of difficulty. Immediately after answering an average of 20 questions on each examination, students predicted their performance on those questions. After assigned subject matter experts had scored the questions, the differences between students' predictions and the experts' scores were calculated for each question. The degree to which students had over- and underestimated their performance across all questions was determined by separately averaging all positive and negative differences between students' and experts' assessments on each examination. The results of the study indicated that accuracy in self-assessment improved from examination 1 to examination 3 (with less overestimation) and dropped on examination 4 (with more underestimation). The results revealed no relationship between self-assessment estimations and actual scores received. Furthermore, the self-assessment estimations tended to be statistically correlated between contiguous examinations (i.e., examinations 1 and 2, 2 and 3, etc.) but not between non-contiguous ones (i.e., examinations 1 and 3, etc.). The results of the study are interpreted to suggest that the students in the study have a self-assessment tendency towards over- or underestimation that is somewhat stable but that gradually evolves over time with experience, maturity and self-assessment practice. The most frequent direction of change is towards decreased overestimation and increased underestimation. These results are consistent with the findings of other recent longitudinal self assessment studies. PMID- 1630334 TI - An analysis of paediatric diagnostic decision-making: how should students be taught? AB - This study assesses the relative importance of history, examination and investigations in paediatric diagnosis, in the Paediatric Out-patient Department of the Central Middlesex Hospital, London, by means of a questionnaire-based record of 94 consecutive referrals. A diagnosis identical to the final diagnosis was made in 76% of referrals after taking a history. The general practitioner had proposed a diagnosis in 45% in the referral letter. Clinical examination changed the diagnosis in only 15% but increased diagnostic confidence in 33%. Ninety-one per cent of cases were diagnosed without recourse to investigations. Forty-two per cent of children referred had investigations performed. In the majority of paediatric cases the provisional diagnosis reached after taking a history was identical to that after examination or results of investigations were known. Although examination provided a final diagnosis in only 15% of all cases it played an important role in adding confidence in 33%. More educational effort should therefore be directed at clinical history-taking skills and the subsequent purpose of examination. PMID- 1630335 TI - The quality of student-tutor interactions in the clinical learning environment. AB - We surveyed 403 students in their clinical years for their perceptions of the quality of clinical clerkships. Between 42.6 and 67.0% of tutorials were said to contain positive factors such as a relaxed teaching atmosphere, enthusiasm, a good selection of patients and adequate preparation. Negative features in 18.2 37.2% of tutorials included unreasonable expectations, conflicting information, late arrival, early departure, failure to show up and the display of anger, a patronizing attitude, favouritism or ridicule. While two-thirds of tutors were regarded as friendly and helpful, the remaining one-third were perceived as unconcerned, discouraging, derogatory or hostile. Overall, only half the clinical tutors were rated as effective teachers; more specifically in medicine and psychiatry, less than one-third of consultants were regarded as effective teachers, as compared with some two-thirds of consultants in obstetrics and gynaecology and paediatrics who were so regarded. Almost two-thirds of the students had predominantly positive reactions to interactions with their tutors, in terms of being motivated to learn, enthused about the subject and having their self-confidence increased. Some one-quarter had negative reactions such as indifference, depression, anger, embarrassment and fearfulness. However, the impact of student-tutor interactions was mainly confined to the students' academic well-being, with little effect on their personal-social lives. Finally, one-third of students had experienced at least some form of mistreatment by their tutors, including gender, appearance, religious and racial discrimination, unfair grading and public humiliation. These findings suggest that the clinical clerkship may not be providing an optimal learning environment for medical students. PMID- 1630336 TI - The decision to enter a medical specialty: timing and stability. AB - The timing and stability of the decision to enter a medical specialty were examined for one class of medical students. Students were asked to predict specialty choices for themselves on six occasions from orientation day in year 1 to January of the senior year. Choices were compared to actual National Residency Matching Programme results. Forty-five per cent predicted their ultimate specialty choice at orientation, and 69% predicted their ultimate choice by the end of the second year. Specialty choices are made early, and are more stable and accurate than the previous literature has suggested. Variations in timing among the specialties are described, and implications for medical education are discussed. PMID- 1630337 TI - Medical education and medical education research and development activities in modern China. AB - The development of medical education in China occurred quite differently to medical education in the rest of the world. A review of the literature has been presented regarding the historical development and the evolution of medical education research and development (MERAD) units in modern China. The history of medical education in modern China has been divided into three periods: (1) the 17 years before the 'Cultural Revolution' (1949-1966); (2) the period of the 'Cultural Revolution' (1966-1976); (3) the post 'Cultural Revolution' period (1976 onwards). Although a number of MERAD activities had existed on China's medical campuses since 1949, there was no formal organizational structure for MERAD before 1978. The change of the political situation in 1978 led China to seek modernization, with education as its basis. In the process of health care system modernization, medical education was given priority, and the Western model of establishing MERAD units as a means of improving the training of health professionals was introduced. The evolution of medical education research and development in modern China appears to be following the Western pattern due to the multitude of Western consultants and fellowships in Western countries provided to Chinese medical education leaders. A group of people from medicine is gathering in the MERAD field and MERAD units are beginning to take shape in modern China. PMID- 1630339 TI - The dismal science and our favourite drug. PMID- 1630338 TI - An introductory 'survival course' for first-year medical students: a brief account of the course. AB - At the School of Medicine, Tromso, Norway, an intensive 2-day week-end course was offered to students in the first year of their studies. The content covered study approaches and study skills, learning issues, strategies for improving the current curriculum, and preparing for the first comprehensive final examination. A brief account of the content and outcome is presented. PMID- 1630341 TI - Medical device regulation in Australia. PMID- 1630340 TI - Alcohol and the brain. PMID- 1630342 TI - Very low energy diets. PMID- 1630343 TI - Alcohol abuse among young offenders. AB - OBJECTIVE: To investigate alcohol use and abuse among young offenders. DESIGN: A questionnaire survey. SETTING: Two centres in Adelaide used for the custodial care of young offenders. PARTICIPANTS: All consecutive admissions involving stays of more than 24 hours. All subjects were adjudicated delinquents. Usable questionnaires were obtained from 197 of the 207 subjects (95.2%) approached. MAIN OUTCOME MEASURE: The Adolescent Alcohol Involvement Scale (AAIS). RESULTS: Most respondents (72.1%) obtained AAIS scores that fell into the problem drinking range, with 24.4% scoring in the "alcoholic-like" drinker category. Comparison with a South Australian student sample indicated much higher rates of alcohol consumption among the young offenders. The majority (56.9%) had been drinking at the time of their last offence. CONCLUSIONS: Offending and the use of alcohol by adolescents are closely linked. Young offenders are at an extremely high risk of alcohol abuse. It is recommended that greater treatment and prevention efforts be directed toward this group. PMID- 1630344 TI - Psychological correlates of the level of alcohol consumption in young adults. AB - OBJECTIVE: To assess the psychological condition of young adults who drank no alcohol, moderate, or excessive amounts of alcohol. DESIGN: Subjects from a longitudinal study of the school-to-work transition supplied information by postal questionnaire, and others matched for age were interviewed. PARTICIPANTS: A sample of adults of average age 24 years. The 483 in the longitudinal study had been students at 12 metropolitan high schools in 1980, and had been followed annually from then until 1988; the 111 who were interviewed were mature-aged university students. Sex ratios and the proportion employed were similar in the two samples. MAIN OUTCOME MEASURES: The General Health Questionnaire was used to measure psychological disturbance in both samples, and alcohol consumption was measured by self-report in terms of number of glasses of beer, wine, spirits and fortified wine taken during the preceding week. RESULTS: Higher levels of disturbance were shown by men who drank excessively in the first study, and who abstained from alcohol in the second study. The latter result was related to the poorer health of abstainers. Women showed no psychological differences according to level of alcohol consumption. CONCLUSIONS: The inconsistent results for men in the two studies suggest that research methodology influences results in ways that are important for researchers in this field to take into account. The lack of disturbance in moderate drinkers of both samples indicates the social acceptability of responsible alcohol consumption in Australia, and supports efforts to educate the public and their medical advisors so that well-informed decisions can be made about alcohol use. PMID- 1630345 TI - Drug use in Australia: a community prevalence study. AB - OBJECTIVE: To estimate the prevalence of drug use in a representative Australian community. DESIGN: Using a Census district sampling framework supplied by the Australian Bureau of Statistics, we randomly selected dwellings for our survey. A household was defined as all those people living permanently at the postal address. All eligible members of each household, 15 years and older, were asked to participate. SETTING: The data were collected in the context of a large scale general population survey of health practices and attitudes, conducted in the Greater Newcastle area of New South Wales, during 1987 and 1988. PARTICIPANTS: Seventy-two per cent of eligible individuals approached (2623) agreed to participate in the survey. MAIN OUTCOME MEASURES: Participants were asked about their use of a number of drug types: medically prescribed drugs, non-prescription drugs, tobacco, alcohol and illicit drugs. For alcohol, only the results for use at a hazardous level according to the National Health and Medical Research Council guidelines are reported here. RESULTS: Seventy-eight per cent (95% confidence interval, 76%-80%) of the community sample reported having recently consumed at least one of these drug types. There were significant age and sex differences in drug use. A greater proportion of women and the older age groups (over 45 years) reported the use of both non-prescription and prescription medications than did men and the younger age groups. Conversely, a significantly greater proportion of men and the younger age groups reported the use of social and illicit drugs. CONCLUSION: The importance of regular, representative, methodologically comparable community studies of drug use is stressed, particularly in view of the inadequacy of the current routine sources of epidemiological data on drug use. PMID- 1630346 TI - Severe obesity: the use of very low energy diets or standard kilojoule restriction diets. AB - OBJECTIVES: To determine the efficacy of two dietary therapies in both the short term (hospitalisation) and the longer term treatment of severe obesity. DESIGN: A descriptive study of two patient groups with obesity defined by a body mass index of greater than 30 kg/m2. SETTING: A multidisciplinary weight control program in a tertiary care hospital. PATIENTS: All admissions to hospital of patients on the weight control program for initiation of weight loss during a period of 48 months. INTERVENTION: A standard kilojoule reduction regimen or the use of complete, followed by partial, long term meal substitution with a very low energy liquid diet (VLED), coupled with an exercise and a behavioural modification program. OUTCOME MEASURES: Weight loss during and after hospitalisation was measured in both dietary regimen groups. RESULTS: Both diets induced weight loss in hospital. Men prescribed VLED lost significantly more weight, 8.3 +/- 0.8 kg (mean +/- SEM) than women prescribed this diet (5.5 +/- 0.5 kg) or standard kilojoule restriction (5.1 +/- 0.8 kg). CONCLUSIONS: VLED and standard kilojoule restriction are both effective for the treatment of severe obesity, particularly in a controlled environment (hospitalisation). In the longer term, VLED is an effective method of maintaining weight loss. Lack of continuing weight loss may reflect the patients who were initially placed on this regimen--small eaters with a presumed high metabolic efficiency. PMID- 1630348 TI - Juvenile myoclonic epilepsy. PMID- 1630349 TI - Computer-assisted learning in medical education. PMID- 1630347 TI - Nebuhaler versus wet aerosol for domiciliary bronchodilator therapy. A multi centre clinical comparison. AB - OBJECTIVE: To compare the clinical effectiveness and patient acceptance of a large spacer device (Nebuhaler) for delivery of metered dose aerosol (MDI) terbutaline with nebulised wet aerosol terbutaline. DESIGN: Randomised open crossover study over two sequential four week treatment periods, following a two week run-in. SETTING: Multi-centre including five adult thoracic units and three paediatric centres throughout Australia. PATIENTS: Thirty-eight adults and 23 children with clinical asthma and reversible airflow obstruction (increase in forced expiratory volume in one second [FEV1] of greater than or equal to 15% in response to inhaled bronchodilator) entered the study proper. Six adults and one child withdrew. INTERVENTIONS: Terbutaline was administered four times daily via Nebuhaler/MDI or nebuliser. Clinical assessment with spirometry and peak flow readings was made after run-in and at the end of each treatment period. Patients recorded on diary cards daily peak expiratory flow rates and symptom scores and comparisons of these results for each treatment period were made. At the completion of the study patients answered a treatment preference questionnaire. RESULTS: No differences were found between the two treatment periods in diary card peak flow recordings and symptom score data, and in clinical assessment of spirometry and peak expiratory flow rates. There were also no differences between spirometry and peak flow values recorded at the clinic at randomisation and at the end of each treatment period, suggesting stable basal airflow obstruction over the period of the study. Thirty-two per cent of adults and 52% of children preferred the Nebuhaler/MDI combination, mainly because of convenience of use. Treatment preference was not related to any measured index of lung function. CONCLUSIONS: MDI terbutaline delivered via Nebuhaler provides clinical benefit similar to that of wet aerosol terbutaline in the long-term domiciliary management of patients with stable airflow obstruction. PMID- 1630350 TI - How are we doing with drugs and alcohol? PMID- 1630352 TI - Punch injuries to the hand in far north Queensland. PMID- 1630353 TI - Medicinal virtues of alcohol in moderation. PMID- 1630351 TI - News in dentistry. PMID- 1630354 TI - Trachoma in Australian aboriginals in the Pilbara. PMID- 1630355 TI - Fulminant hepatic failure complicating the treatment of Mycobacterium xenopi. PMID- 1630357 TI - Prevention in clinical practice: a checklist for general practitioners. PMID- 1630356 TI - Excimer laser photorefractive keratectomy: first Australian series. PMID- 1630358 TI - Catheter-associated urinary tract infections. PMID- 1630359 TI - Cultural variations in mental health. PMID- 1630360 TI - Suburban dogs--a reservoir of human giardiasis? PMID- 1630361 TI - In search of the pathogenesis of refractory cervicobrachial pain syndrome. PMID- 1630362 TI - Neurological complications of sarcoidosis. PMID- 1630363 TI - Silicone breast implants. PMID- 1630364 TI - Tobacco smoking in response to cigarette advertising. PMID- 1630365 TI - Echovirus 16 orchitis and postviral fatigue syndrome. PMID- 1630366 TI - Glue ear and grommets. PMID- 1630367 TI - Munchausen's syndrome. PMID- 1630368 TI - The pursuit of peace. PMID- 1630369 TI - Diet and coronary heart disease. The National Heart Foundation of Australia. AB - Over the last four decades there has been extensive research into the links between diet and coronary heart disease. The most recent literature is reviewed in this position statement. The clinical and public health aspects of the National Heart Foundation's nutrition policy are based on this review. The key points are as follows: 1. Saturated fatty acids A high intake of saturated fatty acids is strongly associated with elevated serum cholesterol and LDL-cholesterol levels and increased risk of coronary heart disease. 2. The n-6 polyunsaturated fatty acids The n-6 polyunsaturated fatty acids (principally linoleic acid) lower serum cholesterol levels when substituted for saturated fats and probably have an independent cholesterol-lowering effect. 3. The n-3 polyunsaturated fatty acids (fish oils) The n-3 polyunsaturated fatty acids reduce serum triglyceride levels, decrease the tendency to thrombosis and may further reduce coronary risk through other mechanisms. 4. Monounsaturated fatty acids Monounsaturated fatty acids reduce serum cholesterol levels when substituted for saturated fatty acids. It is not clear whether this is an independent effect or simply the result of displacement of saturates. 5. Trans fatty acids Trans fatty acids may increase serum cholesterol levels and can be reckoned to be equivalent to saturated fatty acids. 6. Total fat Total fat intake, independent of fatty acid type, is not strongly associated with coronary heart disease but may contribute to obesity. Associations between total fat intake and coronary heart disease are primarily mediated through the saturated fatty acid component. 7. Dietary cholesterol Dietary cholesterol increases serum cholesterol levels in some people and may increase risk of coronary heart disease. 8. Alcohol A high intake of alcohol increases blood pressure and serum triglyceride levels and increases mortality from cardiovascular disease. Light alcohol consumption reduces the risk of coronary heart disease. 9. Sugar The consumption of sugar is not associated with coronary heart disease. 10. Sodium and potassium High salt intake is related to hypertension especially in the subset of "salt-sensitive" people. Potassium intake may be inversely related to hypertension. 11. Overweight and obesity Abdominal obesity increases the risk of coronary heart disease probably by adversely influencing conventional risk factors. 12. Vegetarianism A high intake of plant foods reduces the risk of coronary heart disease through several mechanisms, including lowering serum cholesterol and blood pressure levels. PMID- 1630370 TI - Spontaneously remitting disease. Principles of management. PMID- 1630372 TI - A Borneo experience. PMID- 1630371 TI - Current status of general practice research in Australia. Analysis of a national database. AB - OBJECTIVE: To describe the current status of general practice research activity in Australia. DESIGN: A descriptive survey of research projects included in a national research database, established by the Royal Australian College of General Practitioners. The study instrument was a mailed questionnaire. SETTING AND PARTICIPANTS: Research projects involving or directly related to general practice that had commenced in Australia since 1 January 1989. Responses were specifically sought from all universities, the Family Medicine Programme and the Royal Australian College of General Practitioners. RESULTS: Two hundred and thirty-seven projects from 130 different principal investigators, one-third of whom were not medical practitioners, were analysed. Over 85% of research took place in association with a recognised tertiary institution. Over half of the projects were descriptive only; the most common areas were medical education, prevention and screening and health services research. Of the 69 projects completed prior to 1991, 49 had been submitted for publication and 26 had been accepted. CONCLUSIONS: The amount of general practice research undertaken in Australia is still small in relation to the size of the workforce, and most are descriptive studies. This national database will enable longitudinal changes in such patterns to be effectively monitored. PMID- 1630373 TI - Epidemiology of late presentation of HIV infection in Western Australia. AB - OBJECTIVE: To determine the incidence of and reasons for late presentation of patients infected with the human immunodeficiency virus (HIV), and the demographic characteristics of these late presenters, who first seek medical attention when they have an illness that defines the acquired immunodeficiency syndrome (AIDS). DESIGN: Retrospective analysis of clinical and demographic data relating to 106 sequential AIDS diagnoses in Western Australia. Surviving patients were questioned during routine medical and social work interviews to identify the reasons for late presentation. SETTING: Royal Perth Hospital, the sole specialist referral centre for the management of infection with the human immunodeficiency virus (HIV) in Western Australia. PARTICIPANTS: All patients presenting or referred to Royal Perth Hospital with an AIDS-defining condition between 1 January 1988 and 1 July 1991. RESULTS: Forty-one of 106 (39%) patients presenting with an AIDS-defining condition had known of their HIV status for eight weeks or less (late presenters). The proportion of late presenters decreased from 61% in 1988 to 34% in 1989 (P less than 0.05). Six of the 41 late presenters died during their initial admission compared with only one of the 65 early presenters (P less than 0.02). Sixty-six per cent of late presenters compared with only 35% of early presenters had pneumocystis pneumonia as their AIDS-defining condition (P less than 0.01). There was no significant difference in age at diagnosis of AIDS, martial status, sex or risk factors between the early and late presentation groups. Reasons given for late presentation included lack of knowledge of advances in the treatment of HIV infection, concerns about confidentiality and beliefs that sexual behaviour had been relatively "safe" from risk of HIV infection. CONCLUSIONS: While the proportion of patients presenting late is decreasing, late presentation continues to be a problem. Reasons for delayed presentation are not entirely clear, but can be explained in terms of psychosocial and physiological influences. How and to what degree each of these contribute to timing of presentation is yet to be determined. PMID- 1630374 TI - Mycobacterial disease and AIDS in New South Wales. AB - OBJECTIVE: To determine the coincidence of mycobacterial disease and acquired immunodeficiency syndrome (AIDS), and whether persons with mycobacterial disease and human immunodeficiency virus (HIV) infection differ from those with mycobacterial disease alone, by age, sex and country of birth. DESIGN: A descriptive study. PARTICIPANTS: Persons on the NSW Tuberculosis Register in 1989 and those on the NSW AIDS database in 1982-1989. MAIN OUTCOME MEASURE: Coincident appearance on the Tuberculosis Register and the AIDS database. RESULTS: People with atypical mycobacterial infection and HIV infection were younger and more likely to be male compared with those with mycobacterial disease alone. There was a strong association between mycobacterial disease and HIV infection. Of 438 patients newly diagnosed with mycobacterial disease in 1989, 75 (17.1%) had HIV infection. Of 318 tuberculosis patients, 8 (2.5%) had HIV infection, and of 120 patients with atypical mycobacterial infection, 67 (55.8%) had HIV infection. CONCLUSION: Close monitoring of HIV patients for mycobacterial infection, and chemoprophylaxis for persons infected with HIV who have positive Mantoux test results will assist in the control of mycobacterial disease. HIV testing and counselling should be considered for all persons with mycobacterial disease. PMID- 1630375 TI - Predicting AIDS deaths and prevalence in Australia. AB - OBJECTIVE: To describe a method for predicting deaths from, and the prevalence of, the acquired immunodeficiency syndrome (AIDS) in Australia and to obtain ranges of projections for the next five years based on data observed to 30 September 1989 and reported by January 1990. The projections are important components of planning for future health-care needs. PATIENTS: All patients with AIDS in Australia who were known to the National Centre in HIV Epidemiology and Clinical Research. The data used in the analysis were date of diagnosis of AIDS, date of death if the patient had died, and State or Territory of diagnosis. RESULTS: For Australia as a whole, the doubling time of AIDS incidence changed from 0.83 years before mid 1987 to 4.34 years after that time. Five hundred and seventy patients were diagnosed with AIDS to 30 June 1987 of whom 487 had died by 30 September 1989 and the estimated mean survival time was 1.36 years. Of 1037 patients diagnosed with AIDS after June 1987, 352 had died and the estimated mean survival time was 2.42 years. Combining the estimated survival distribution with the projected new cases of AIDS, we forecast that there will be between 530 and 680 deaths from AIDS in Australia in the year mid 1991 to mid 1992. Estimated cumulative deaths to mid 1994 range from 3390 to 4250. We predict that there will be between 1370 and 1850 people living with AIDS during the year ending mid 1992, and that this number will increase to between 1760 and 2830 for the year ending mid 1994. We also predict that the prevalence of AIDS in New South Wales will lie between 820 and 1620 for the year ending mid 1994, and that the prevalence in Victoria will lie between 270 and 740 in the same year. CONCLUSIONS: Any value in the range of predictions for AIDS incidence we give is equally likely and there is good agreement with the data now observed from mid 1989 to mid 1990. The dramatic increase in the doubling time is the result of a number of factors predicted by epidemic theory and the availability of treatment, zidovudine in particular. Our estimates of deaths and prevalence have been influenced by the quality of the available death data. The observed number of deaths in the year mid 1989 to mid 1990 has exceeded the number forecast for that year. Substantial improvements in survival were associated with the introduction of zidovudine into clinical practice in mid 1987 but the death rate has risen rapidly again in the very recent past, possibly due to patients becoming increasingly refractory to treatment with zidovudine (before or after a diagnosis of AIDS). Our approach to forecasting can be adjusted to accommodate a transient effect of treatment as further data accumulate. PMID- 1630376 TI - Basic immunology of transplantation. PMID- 1630377 TI - Mortality of former prisoners of war and other Australian veterans. AB - OBJECTIVE: This second summary article from an epidemiological review of the health of former prisoners of war (POWs) and other Australian veterans, commissioned by the Sir Edward Dunlop Medical Research Foundation, reports on studies of mortality. DATA SOURCES: The MEDLARS database, from 1966 to the present, under the terms military personnel, veterans, veterans' disability claims, combat disorders and prisoners (matched against war); databases of the Department of Veterans' Affairs (Victoria) and the Central Library, Commonwealth Department of Defense, under the term "prisoner of war"; and the microfiche listings of the Department of Veterans' Affairs, under "prisoner of war" and "repatriation". Only studies in English or French were reviewed, reaching a total of 172. STUDY SELECTION: Four studies in this paper constitute the main evidence about postwar mortality in Australians who were POWs of World War II or Vietnam veterans. Other mortality studies are cited in the complete literature review published elsewhere. DATA EXTRACTION: Only the data with an epidemiological basis are considered here. DATA SYNTHESIS: All-cause mortality rates were no greater in former POWs or Vietnam veterans than in the general Australian male population. There was, however, evidence of increased mortality among former POWs compared with other non-POW veterans, and among Vietnam veterans in one particular corps compared with veterans of the same era who served in Australia. CONCLUSIONS: Elevated early postwar mortality of young former POWs implicates diseases with short latent periods (including psychiatric disorders). This is consistent with the greater health risks of this group of survivors that were identified in the earlier review of morbidity. Mortality among former POWs and other veterans requires continued surveillance because a "healthy worker effect" (or exclusion of unfit persons from the armed forces) may partly conceal increased morbidity or mortality that should be attributed to war service. PMID- 1630378 TI - Antiretroviral agents in the nineties. PMID- 1630379 TI - Envenomated? Always check the bite site. PMID- 1630380 TI - Envenomation by the small-scaled snake: the world's most venomous snake. PMID- 1630381 TI - Patients with ciguatera: request for convalescent sera. PMID- 1630382 TI - Of spines, braces and steel rods. PMID- 1630383 TI - Treatment of ventricular arrhythmias after CAST. PMID- 1630384 TI - Proper use of the waist to hip ratio. PMID- 1630385 TI - The use of corticosteroids in dermatological practice. PMID- 1630386 TI - Tuberculosis in Australia. PMID- 1630387 TI - Tuberculosis in Australia. PMID- 1630388 TI - Emergencies in general practice. PMID- 1630389 TI - Emergencies in general practice. PMID- 1630390 TI - Eradication of Legionnaires' disease. PMID- 1630391 TI - Peripheral oedema associated with moclobemide. PMID- 1630392 TI - Thrombolytic therapy for coronary occlusion. PMID- 1630393 TI - Anticoagulants for atrial fibrillation. PMID- 1630394 TI - Treatment of atrial fibrillation: time for change? PMID- 1630395 TI - Changes in drug treatment and case fatality of patients with acute myocardial infarction. Observations from the Newcastle MONICA Project, 1984/1985 to 1988/1990. AB - OBJECTIVE: To describe changes in medications administered to patients with acute myocardial infarction between 1984/1985 and 1988/1990 and changes in case fatality. DESIGN: Descriptive study from the Newcastle MONICA Project, which monitors all heart attacks in men and women aged 25 to 69 years in the Lower Hunter Region of New South Wales. SUBJECTS: All patients admitted to hospital with a "definite" acute myocardial infarction who survived at least 28 days during periods in 1984/1985 (513 events) and 1988/1990 (790 events). MAIN OUTCOME MEASURES: Changes in drugs being taken immediately before the onset of the myocardial infarction, prescribed during hospitalisation and on discharge from hospital, and changes in case fatality rates. RESULTS: From the first time period to the second there were significant increases in the use of aspirin, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors and hypolipidaemic agents, and significant reductions in the use of diuretics. In 1988/1990, 34% of patients with a definite myocardial infarction received thrombolytic therapy compared with fewer than 1% in 1984/1985. Among those patients who survived at least one hour from onset of symptoms, the case fatality rate declined from 13.5% to 7.9% (change -5.6%; 95% confidence limits, -8.9%, 2.2%). CONCLUSION: Large changes in drug treatment of patients with acute myocardial infarction have occurred in the second half of the 1980s. These may be responsible for the reduction in case fatality. Nevertheless, use of drugs of proven effectiveness in acute care and for secondary prevention is surprisingly low in this population. PMID- 1630396 TI - Transfusion of frozen thawed blood stored at -20 degrees C to -25 degrees C. AB - OBJECTIVE: To determine the clinical efficacy of transfusion of frozen-thawed (FT) red cells using a 5-bag system for freezing (at -20 degrees C to -25 degrees C), storage and reconstitution. DESIGN: A prospective, controlled, non-randomised clinical trial was undertaken with two groups of orthopaedic surgical patients. Nine patients received FT homologous blood and a control group of 10 patients received homologous blood stored in liquid form at 4 degrees C. Five transfusion dependent patients with medical conditions were also studied. OUTCOME: Thirty three FT units were transfused without incident to 14 patients. In addition to clinical assessment, haematological and biochemical parameters were monitored after transfusion. There were no clinical side effects and laboratory data were consistent with those after recent surgery or for pre-existing medical conditions and subsequent blood transfusion. On the practical side certain technical difficulties were encountered which improved with experience. CONCLUSIONS: One of the major advantages of the system is the 35-day shelf-life at 4 degrees C after reconstitution. This system has potential for pre-deposit autologous collection, especially where large volume replacement may be required. PMID- 1630397 TI - Some characteristics of blood shed into the Solcotrans postoperative orthopaedic drainage/reinfusion system. AB - OBJECTIVE: To assess the suitability of blood shed into the Solcotrans orthopaedic autotransfusion system as a source of autologous blood for transfusion. DESIGN: Blood samples were taken from patients after surgery and from shed blood within the Solcotrans units. SETTING: Surgery was performed at a public hospital. PATIENTS: All six patients underwent total knee replacements. MAIN OUTCOME MEASURES: Measurements were made of haemoglobin, haematocrit, platelets, pH, potassium, plasma haemoglobin, fibrinogen, D-dimer, plasminogen activator, thromboplastin and fibrinopeptide A. The non-activated partial thromboplastin time was estimated. Shed blood was compared with homologous whole blood to assess the thrombogenic potential of shed blood in vitro. RESULTS: The haemoglobin and haematocrit levels of the shed blood were significantly lower than venous blood (P = 0.008). Levels of potassium in shed blood were normal although there was significant haemolysis. Shed blood was depleted of clotting factors, with increased levels of D-dimer (16-128 g/L). Activation of the coagulation pathway within the shed blood was shown by a shortened non-activated partial thromboplastin time (90-120 s), and detectable levels of thromboplastin. Propionibacterium acnes was isolated from one of the units. CONCLUSION: Reinfusion of large volumes of shed blood should probably be avoided, but use of the Solcotrans orthopaedic transfusion system in conjunction with other autologous transfusion practices can reduce the patient's requirement for homologous blood. PMID- 1630398 TI - Haematological profile of healthy elderly Australians. AB - OBJECTIVE: To determine normal values for haematological parameters in healthy elderly persons, and document any changes in these over a 12 month period. DESIGN: The study was conducted as part of a randomised controlled trial of low dose aspirin for primary prevention of cardiovascular disease in the elderly. All participants (380) had a full blood examination performed at entry, which was repeated after 12 months. The baseline results for all patients and the 12 month findings in a cohort of 162 persons allocated placebo were used in the present study. SETTING: Community-based (general practices and residential retirement villages). SUBJECTS: Persons aged 70 years and over (53% females) who were ambulatory, living independently, and volunteered to participate. None had significant vascular disease, peptic ulceration, haemorrhagic symptoms or were currently taking non-steroidal anti-inflammatory drugs. MAIN OUTCOME MEASURES: Full blood examination (excluding white cell differential counts) performed with a Technicon H1 analyser. RESULTS: The mean haemoglobin level +/- standard deviation (SD) was 14.69 +/- 1.10 g/dL (for men) and 13.72 +/- 1.05 g/dL (for women). Significant differences (P less than 0.001) in packed cell volume, red cell and platelet counts were observed between the two sexes. No clinically significant change was observed in any of the parameters over a 12 month period. CONCLUSIONS: Haematological reference values for healthy elderly Australians are consistent with normal values reported in younger populations for both sexes. As a result recommendations are provided for normal reference values among this group in an Australian setting. PMID- 1630399 TI - [Solvent pollution in shoe factories]. AB - In order to study solvent exposure in shoe factories, 43 kinds of glues and 22 solvent products used in footwear manufacturing were analyzed. A gas chromatographic spectrometric method was used to identify the mixtures of solvents contained in glues and their diluents. Acetone, ethylacetate and cyclohexane were the solvents more frequently found in glues. Cyclohexane represented on average about 40% of the solvent mixture. Methyl ethyl ketone, 3 methylpentane and 2-methylpentane were often present in glues (45-52% of the samples), but only in a few cases were they associated with n-hexane. N-hexane and methylcyclopentane were found in 32% of the glue samples. N-hexane represented 47% of the solvents only in one glue. Most of the glues contained less than 10% n-hexane. Other solvents (dichloropropane, toluene, trichloroethane, butyl acetate, iso-butyl acetate and 2,2-dimethylbutane) were found in few glue samples or in low percentages. The 22 solvents used as glue diluents were mainly acetone, ethylacetate, dichloromethane and methyl ethyl ketone. The results suggest that solvent exposure in shoe factories has changed compared with data reported about 10 years ago. Biological monitoring of shoe factory workers should measure exposures to the specific solvents found in each factory, especially acetone, cyclohexane, ethylacetate and methyl ethyl ketone. PMID- 1630400 TI - [The report on a divisional plan as an evaluation of results]. AB - The adoption of norms of recommended practice (NRP) by industrial management (a fundamental step in ensuring a safer and healthier work environment, is in our opinion a suitable approach for evaluating primary prevention programmes. We tested this hypothesis in the shoe and leather goods manufacturing industry (55 facilities). An ordinal scale was defined for each variable taken into account by NRP and for other variables related to employers' actions. A score was assigned to every facility with reference to the starting and ending points of the programme. In this way we estimated the degree of variation, in time and among facilities, in adopting NRP. PMID- 1630401 TI - [The determination of serum amino-terminal procollagen type-III propeptide (PIIINP) in occupational exposure to rock wool fiber]. AB - Fifty-six males workers exposed to rock wool during production, and 20 referents were examined. Exposure, evaluated by personal sampling, ranged from 0.05 to 0.74 fibres/ml (median 0.15). The subjects underwent a medical examination, chest X ray according to ILO recommendations and pulmonary function tests. In all subjects the serum levels of type III procollagen N-terminal propeptide (PIIINPs) were determined. No evidence of pulmonary fibrosis, nor work-related lung diseases were observed. PIIINPs mean values in the exposed (9.8 ng/ml; 2.8 S.D.) were slightly higher, but not significantly different when compared to referents (8.5 ng/ml; 2.5 S.D.). No significant correlation between PIIINPs and rock wool exposure (both airborne levels and exposure duration) was observed. Furthermore, peptide levels were not related to pulmonary function test results. Our results suggest that occupational exposure to rock wool fibres lower than 0.75 fibres/ml for less than 20 years does not induce definite cases of pulmonary fibrosis nor an increase of type III collagen synthesis in the lung. PMID- 1630403 TI - Occupational accidents in a selected chemical enterprise in Poland and an attempt to evaluate their economic effects. AB - An analysis was made of occupational accidents leading to temporary absence from work occurring in a selected chemical plant in the years 1988-1989. The authors also studied the possibilities of evaluating costs and financial losses for the enterprise due to occupational accidents. However, the results of the evaluation, in the Polish situation and based on records existing in the enterprise, were not very useful. PMID- 1630402 TI - [The monitoring of cholinesterases in farm workers and tradesmen exposed to phosphoric esters and carbamates]. AB - Cholinesterase (ChE) levels (Ellman method) were monitored in 90 subjects (69 males and 21 females) exposed to carbamate and organophosphate pesticides (78 agricultural workers and 12 pesticide vendors). Pre-exposure baseline values of plasma and red blood cell cholinesterase activities were defined for each subject with two blood samples (23 workers) or three blood samples (59 workers) taken almost thirty days after the last exposure. After control of intra-individual variation, 8 subjects with only one pre-exposure value and 13 with a coefficient of variation above 30% were excluded. For the other 59 subjects, the intra individual variation of erythrocyte ChE (16%) was similar to the inter-individual one (15%), whereas the inter-individual variation of plasma ChE (21%) was higher than the intra-individual one (14%). Laboratory variation for plasma ChE measurements was 8%. Baseline values were analyzed (ANOVA) for sex, age, task and hour and season of sampling. Both erythrocyte and plasma enzymes, corrected for hematocrit, were lower in females. Plasma cholinesterase activity was lower in "re-entry" agricultural workers and in pesticide vendors. Post-exposure cholinesterase activity was measured in 54 workers within a few (1-21) days after last handling. Average relative reduction was 15.2% (95% C.I. = 4.9%-25.5%) in erythrocyte cholinesterase activity and 29.1% (95% C.I. = 18.2%-40.1%) in plasma cholinesterase activity. The one-way variance analysis showed marked plasma ChE reduction in mixers, loaders and appliers (36%, 95% C.I. = 24%-48%) and in parathion handlers (35%, 95% C.I. = 21%-49%. No significant reduction in blood cell cholinesterase activity in relation to task and to pesticide handled was observed. We conclude that the intra-individual variations of the baseline values were higher for three repetitions (88% and 84% of the population were within a variability of less than 30%, for AChE and for ChE respectively) than for two repetitions (91% and 88% of the population were within 30% of variability for AChE and for ChE respectively). The figures show a greater sensitivity of plasma ChE activity in acute exposure, probably due to a poor reliability in detection of erythrocyte ChE by local laboratories. The maximum reduction (38%, 95% C.I. = 22%-53%) in plasma ChE activity was observed within six days of the last exposure in loaders and appliers. PMID- 1630404 TI - Monitoring of peak expiratory flow rates during occupational asthma treatment. AB - The purpose of this study was to evaluate the effect of anti-inflammatory drug treatment on respiratory symptoms and lung function in twelve subjects with occupational asthma while at work. PEFR was monitored for four weeks and antiasthmatic drugs (salbutamol, chromolyn sodium and beclomethasone dipropionate) were administered for three weeks, starting after the first week of PEFR monitoring, in an unchanged working environment. After treatment five subjects became asymptomatic, six improved and one continued to have unchanged work-related asthmatic symptoms. There were only minor increases in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and mean forced expiratory flow during the middle half of FVC (FEF25-75). Bronchial reactivity was studied in eleven subjects: six worsened and five improved. PEFR at 0600 h increased by 9.4% in nine responders and decreased by 5.8% in three non-responders. After treatment diurnal variation (DV) in PEFR decreased by 28.4% in responders and 30.8% in non-responders, even if at the fourth week it was 1.75 higher in non responders compared to responders. In conclusion, in this study a continuous treatment of occupational asthma with anti-inflammatory drugs minimized respiratory symptoms, slightly increased PEFR and greatly reduced DV in PEFR. PMID- 1630405 TI - [Lymphocyte subpopulations in workers exposed occupationally to styrene]. AB - In a group of 32 workers occupationally exposed to styrene, the distribution of lymphocyte subsets was investigated by automated flow cytometry. The group under study consisted of 22 male and 10 female workers aged 39.7, D.S. = 10 years and employed for 6.8 years in factories manufacturing glass fibre-reinforced plastics. A control group (12 males and 7 females) recruited according to the same selection criteria was simultaneously examined. Environmental and biological monitoring was used to characterize styrene exposure. In styrene-exposed workers, phenotypic analysis of peripheral blood revealed a reduced proportion of T helper lymphocytes and a relative increase in the T suppressor subset, leading to a significant inversion of the helper/suppressor ratio (0.92) among heavily exposed workers (greater than 50 ppm, 8h-TWA) as compared to less exposed workers and controls (1.37 and 1.43 respectively). The proportion of natural killer (NK) T lymphocytes was significantly increased among styrene workers. The proportion of B lymphocytes was unchanged as compared to the control group. Dose-response relationships were clearly apparent for the observed increases in the prevalence of abnormalities: none of control subjects showed more than 2 (out of 8) abnormal values as compared to 20 and 40% of styrene workers belonging respectively to the low and high exposure group (p less than 0.007). Only a minority of controls exhibited abnormally high levels of both NK and suppressor T lymphocytes (0-5%), the corresponding figures for styrene workers being 7-10% (low exposure) and 45% (high exposure). As a whole, the findings support the hypothesis of the immunotoxicity of styrene, which could be due either to direct effects on lymphocytes or to indirect mechanisms possibly mediated by neuroendocrine changes. PMID- 1630406 TI - [Pleural fibrosis in asbestosis and ventilatory function: a study of 50 cases]. AB - The importance of non-malignant pleural fibrosis in asbestosis in relation to respiratory function is still open to debate because of the differing results obtained in studies of different population groups. In the present study we selected 50 subjects with occupational exposure to asbestos presenting mono- or bilateral pleural fibrosis at X-ray but without lung impairment. Each subject underwent bronchial lavage and ventilatory function tests. The subjects were divided into 4 groups on the basis of the degree of pleural alterations according to the ILO Classification of Pneumoconioses. The results revealed that the mean values of CV and FEV1 in each group were within physiological limits. Moreover, analysis of the type of lung function showed a normal situation in 64% and restricted function in 28% of the cases. The prevalence of the latter finding was not correlated to the severity of pleural fibrosis in the various groups. Also, comparison between severity of pleural fibrosis and number of asbestos bodies/ml of BAL liquid on the one hand and frequency of alveolitis on the other did not reveal any relationship. Therefore, the onset of pleural fibrosis appears to be independent of the quantity of inhaled asbestos fibres and due to different mechanisms from those leading to lung fibrosis. In practice, a correct interpretation of the presence of pleural fibrosis from a clinical and prognostic viewpoint also requires other investigations such as BAL and a complete respiratory function study. PMID- 1630408 TI - [The untenable thoughtlessness of some legal judgements on the matter of occupational tumors]. PMID- 1630407 TI - [Auditory evoked potentials in workers exposed to styrene]. PMID- 1630409 TI - [The mechanisms of toxicity and risk assessment]. PMID- 1630410 TI - [Exposure to asbestos and Decree 277]. PMID- 1630411 TI - Flecainide for supraventricular tachyarrhythmias. PMID- 1630412 TI - Post-natal development of sleep organization in man: speculations on the emergence of the 'S process'. AB - We outline the development during the first year of life of both sleep-wake patterns and internal sleep organization (sleep states, quiet sleep-paradoxical sleep cycles, and slow-wave sleep), and raise the issue of the emergence of the 'S process'. The consolidation of sleep in episodes of longer duration takes place during the night; the ability to maintain sleep after sleep onset decreases during the day in infants older than 6 months. The main contribution to the increase of longest nocturnal sleep episode duration comes from the quiet sleep, the number of quiet sleep-paradoxical sleep cycles being of minor importance. The temporal analysis of infant sleep structure showed a difference between the first and the following cycles, not only for slow wave activity in infants older than five months, but also for younger infants and for other individual physiological activities (EEG activity, respiratory and cardiac rates): is the early development of these peculiar features a sketch of the 'S Process' described in the adult? PMID- 1630413 TI - [Functions of paradoxical sleep and ontogenesis]. AB - The hypotheses directly linked to cognitive and neurologic ontogenic processes ie consolidation of memory and learning, the maturation hypothesis of Roffwarg and the hypothesis of endogenous genetic programming of Jouvet, are analysed. The discussion of these theories are based on the analysis of: the neurophysiologic mechanism of REM sleep and its ontogenesis in human, the results of REM sleep deprivation in young animals and by a personal study of facial mimics during sleep in neonates. Active sleep could be assimilated, very early during ontogenesis, to REM sleep, it probably plays an important role in brain maturation during early development but the stimulation is probably, at this time, not very specific, later it could be a link between genetic programming and epigenetic processes. PMID- 1630414 TI - [Automatic analysis of sleep-wake states during the first year of life]. AB - Automatic analysis on infant sleep tracing was first considered as an aid to the rapid construction of hypnograms. It has long been thought more complicated than in adults, because of the significant changes in electrogenesis during the first year of life, resulting in difficulty to adapt to the criteria of Rechtschaffen and Kales (1968), even if modified, or to those of Anders et al (1971). In fact, these studies have shown that automatic analysis of sleep EEG tracings permit an easier analysis of the changes in electrogenesis according to subject age, sleep stage and time of night. Moreover, automatic analysis of parameters which change with the sleep-wake stages shows the continuity of these changes, and therefore the somewhat arbitrary nature of conventional hypnogram classification. The mathematical treatment of this information facilitates their visualisation, and permits a better analysis of circadian and ultradian variations that could scarcely be formalized by classical hypnogram analysis. In the study of maturation occurring during the first months of life, automatic signal processing will require adaptation that will lead to new forms of reasoning. PMID- 1630415 TI - Physiological correlates of sleep development in premature and full-term neonates. AB - Differentiation of motor and automatic function control during different sleep states appears early in human ontogeny. Time of first appearance, magnitude of between-state differences and modifications with age depend on which particular parameters are considered. For some parameters, significant between-state differences appear at 31 weeks conceptional age (wk CA). For nearly all parameters, this difference is clear from 35 wk CA onwards. The analysis presented herein is based on studies of body movements, spontaneous skin potential responses, respiratory characteristics, heart rate and heart rate variability, and correlations between different functions. It examines clinically and neurologically normal premature and full-term neonates of 28-41 wk CA. PMID- 1630416 TI - [The frequency of respiratory variations during daytime and nighttime sleep in 35 normal 2-month-old infants]. AB - Daytime and nighttime polygraphic recordings were made of 35 normal 2-month-old infants. Respiratory rate was calculated every minute in active (AS) and quiet (QS) sleep states. The study indicates a difference in mean rate between the 2 states and also shows that mean respiratory rate was lower at night than during the day (P less than 0.0001 for both states) and that there was a marked increase in rate during the first cycle. Infants with episodes of periodic breathing had a lower mean respiratory rate throughout the recordings. For each QS phase, both day and night, a marked decrease in mean respiratory rate occurred, especially during the first part of the sleep state, which was not found in AS. Intrasleep spontaneous awakening led to a marked increase in respiratory rate after sleep was resumed both in QS and AS. However, differences were only statistically significant when the awakened infant was fed. There was less difference between respiratory rates after spontaneous awakening without feeding since the pre awakening rate was more elevated than when the infant was subsequently fed. PMID- 1630417 TI - [Development in the metabolism of dopamine and its derivatives. Application to gross development disorders]. AB - Dopamine (DA) and its metabolites homovanillic acid (HVA) in total, free and conjugated forms, dihydroxyphenylacetic acid (DOPAC) in total, free and conjugated forms, and 3 methoxytyramine (3 MT) levels were determined in the urine of autistic children from 2 years 8 months to 12 years of age and compared to those in normal children of identical age. Very significant group and age effects were found for DA, HVA and 3 MT. In the discussion, results are related to the hypothesis of a disorder in the maturation of the dopaminergic systems in infantile autism. PMID- 1630418 TI - Seat belt usage by trauma center personnel. PMID- 1630419 TI - Recent trends in the selection and fitting of hearing aids. AB - A large segment of the hearing impaired population does not utilize amplification. this paper reviews several factors which may account for the under utilization of hearing aids by the hearing impaired population. In addition, this paper reviews several recent developments in procedures used to select and fit hearing aids. PMID- 1630420 TI - We must be involved in the decisions that will determine medicine's role in society. PMID- 1630421 TI - U.S. Department of Health and Human Services issues final Medicare and Medicaid anti-kickback safe harbor regulations. PMID- 1630422 TI - MOMEDICO: an answer to a need. PMID- 1630423 TI - Is the PRO a quack? PMID- 1630424 TI - Invasive pulmonary aspergillosis complicated by nocardiosis in a patient with agnogenic myeloid metaplasia. PMID- 1630425 TI - Prevention and control of tuberculosis in migrant farm workers. Recommendations of the Advisory Council for the Elimination of Tuberculosis. AB - Farm workers are approximately six times more likely to develop tuberculosis (TB) than the general population of employed adults. These recommendations are presented to assist health-care providers serving migrant and seasonal farm workers. The following services, listed by priority, that should be available for migrant and seasonal farm workers and their family members are: a) detection and diagnosis of those with current symptoms of active TB; b) appropriate treatment and monitoring for those who have current disease; c) contact investigation and appropriate preventive therapy for those exposed to infectious persons; d) screening and appropriate preventive therapy for asymptomatically infected workers who may be immunosuppressed, such as those with human immunodeficiency virus (HIV) infection; e) screening and appropriate preventive therapy for children of migrant and seasonal farm workers; and f) widespread tuberculin test screening for workers and families with preventive therapy prescribed, as appropriate. Health-care providers should immediately perform appropriate diagnostic studies for persons with a productive, prolonged cough, or other symptoms suggestive of tuberculosis. Health departments should be immediately notified when TB is suspected or diagnosed to enable examination of contacts and initiation of other health department diagnostic, preventive, or patient management services. Workers and family members with uncomplicated pulmonary TB should be treated with a regimen that includes isoniazid, rifampin, pyrazinamide, and ethambutol (or streptomycin). Drug-resistant TB is an important consideration since it requires altered treatment regimes and because higher rates of resistance have been found in ethnic and social groups comprising much of the migrant farm worker-force. Patients should be monitored carefully for compliance, treatment response, and toxicity. Ideally, patients should be placed on directly observed therapy given by a well-trained, outreach worker from the same cultural/language background as the patients. PMID- 1630426 TI - Lyme disease knowledge, attitudes, and behaviors--Connecticut, 1992. AB - Lyme disease (LD), caused by infection with the spirochete Borrelia burgdorferi, is the most commonly reported tick-borne illness in the United States (1). Because no vaccine is available and effective measures to control tick populations are experimental, education is the most important approach to preventing LD. LD was identified in Connecticut in 1975 (2); in 1991, Connecticut had the highest rate of LD in the United States (36 per 100,000 population), and cases were reported in residents from 134 of Connecticut's 169 cities. To assess knowledge, attitudes, and behaviors related to LD, the State of Connecticut Department of Health Services and the University of Connecticut conducted a telephone survey of adults in Connecticut during the first 2 weeks of May 1992. This report summarizes the results of the survey. PMID- 1630427 TI - Transmission of multidrug-resistant tuberculosis among immunocompromised persons in a correctional system--New York, 1991. AB - During 1990 and 1991, nosocomial transmission of multidrug-resistant tuberculosis (MDR-TB) was documented in four hospitals in New York and Florida. Subsequently, additional MDR-TB outbreaks have been investigated by CDC. This report summarizes preliminary results of an investigation of transmission of MDR-TB in a correctional facility in New York. PMID- 1630428 TI - Sudden infant death syndrome--United States, 1980-1988. AB - Sudden infant death syndrome (SIDS) (the abrupt and unexplained death of an apparently healthy infant) is the second leading cause of infant mortality in the United States (1) and the eighth leading cause of years of potential life lost (2). This report analyzes race- and region-specific data for SIDS during 1980 1988. PMID- 1630429 TI - Outbreak of type E botulism associated with an uneviscerated, salt-cured fish product--New Jersey, 1992. AB - In May 1992, the New Jersey Department of Health (NJDH) received a report of a man admitted to a hospital with a preliminary diagnosis of botulism. Subsequently, three family members of the man were diagnosed with botulism. This report summarizes the epidemiologic investigation of these cases that linked illness to consumption of an uneviscerated, salt-cured fish product.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630430 TI - Public-sector vaccination efforts in response to the resurgence of measles among preschool-aged children--United States, 1989-1991. AB - From 1989 through 1991, in the United States, the incidence of reported measles increased sixfold to ninefold over the median annual incidence (1.3 per 100,000 population) reported from 1981 through 1988. In 1990, the peak of the resurgence, the incidence of measles among children aged less than 5 years was 15-fold higher than the median 1981-1988 incidence (4.8 per 100,000) (1). During 1991, approximately 9500 cases were reported (Figure 1), including 4662 cases among children aged less than 5 years (CDC, unpublished data). The measles epidemic is a consequence primarily of the failure to vaccinate preschool-aged children at appropriate ages (2); among children aged 16-59 months who developed measles during this resurgence, only 15% had received measles vaccine as recommended (CDC, unpublished data). This report compares the number of public clinic vaccinations* (i.e., all measles-containing vaccines [MCV], diphtheria-tetanus pertussis vaccine [DTP], and oral polio vaccine [OPV]) for 1988 with that for 1989-1991 in response to the measles resurgence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630431 TI - Coronary heart disease incidence, by sex--United States, 1971-1987. AB - Coronary heart disease (CHD) is the leading cause of death in the United States for both men and women, although the rates are lower among women (1). The incidence of CHD, however, has not been as well characterized among women as it has among men (2). This report presents data on sex-specific incidence of CHD and the risks associated with smoking, diabetes, hypertension, total cholesterol, body mass, and age using data from the Epidemiologic Follow-up Study of the First National Health and Nutrition Examination Survey (NHEFS) (3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630432 TI - Estimated national spending on prevention--United States, 1988. AB - Despite the overall health improvements achieved through preventive interventions, the United States continues to be burdened by preventable illness, injury, and disability (1). For example, annual health-care expenditures for cardiovascular disease alone exceed $135 billion and injury and disability, $170 billion (1). This report summarizes the findings of a study to estimate national funding for health promotion and disease prevention in the United States during 1988 (2). PMID- 1630433 TI - [Studies on changes in low esophageal sphincter function after esophageal transection or esophago-esophagostomy in children]. AB - An aim of the present study is to clarify the changes of esophageal function after surgical treatments of the esophageal varices or the congenital esophageal stenosis in children. Esophageal manometric studies were performed in sixteen children undergoing the esophageal transection with paraesophageal devascularization or the esophago-esophagostomy with partial esophagectomy before, within 1 month and over 7 months after the operation. The pressure of lower esophageal sphincter (LES), the length of LES, the LES relaxation test and the gastroesophageal reflux (GER) inducing test were measured. 1) Esophageal transection; The pressure dropped within 1 month and returned to the preoperative level over 11 months after the operation. Temporal deterioration of LES function was observed during the early postoperative days. However, return to the preoperative state was gained over 1 year. 2) Esophago-esophagostomy; The pressure and the length of LES were not changed after the operation. The LES function was disturbed preoperatively and moreover long postoperatively, in the case when congenital stenosis closely existed to the esophago-gastric junction. Degree of the postoperative disturbance of the LES function may be influenced by the distance to the part of the transection or the partial esophagectomy from the E-C junction. PMID- 1630434 TI - [Clinical study on responses of the upper esophageal sphincter after subtotal esophagectomy for esophageal cancer]. AB - Responses of the upper esophageal sphincter (UES) to distention of the esophageal wall by use of a balloon catheter were measured in 30 patients after subtotal esophagectomy for esophageal cancer and 33 volunteers with unrelated disorders (control group). Patients were divided into extended dissection group and non extended dissection group according to the width of lymph node dissection, or palsy group and non-palsy group according to recurrent-laryngeal nerve palsy. The resting upper esophageal sphincter pressure (UESP) and the upper esophageal sphincter contraction (UESC) following UES induced by swallowing were measured after esophageal distention. Neither of UESP nor UESC without distention was significantly different among each group. But those of the extended dissection group and palsy group after esophageal distention were significantly lower values than those of control group. These findings suggest that responses of the UES to distention of esophageal wall are decreased, thus protection against aspiration is probably decreased. PMID- 1630435 TI - [Experimental studies on the effects of alpha-tocopherol in small intestinal ischemia and reperfusion injury]. AB - In the present study, we quantified the biochemical [thiobarbituric acid (TBA) reactants, superoxide dismutase (SOD) and vitamin E] and histologic changes in the small intestinal tissue after ischemia and/or reperfusion. Sixty-seven Wistar rats were divided into 7 groups; N group: control, A-I group: 30 min. ischemia, A II group: 120 min. ischemia, B-I group: Declamp after 30 min. ischemia, B-II group: 30 min. reperfusion after 30 min. ischemia, B-III group: 30 min. reperfusion after 120 min. ischemia, E group: vitamin E administration 30 min. reperfusion after 30 min. ischemia. The levels of TBA reactants were significantly different between A-II and B-II, B-II and E (all p less than 0.01). For SOD, there were significant differences between N and B-I (p less than 0.01), N and E (p less than 0.05). For vitamin E, there were significant differences between A-I and B-I, A-I and B-I, B-II and E (all p less than 0.01). Histologic changes showed that the grade of tissue injury was more severe in B-I and B-II than in A-I, and was less in E than in B-II. It is suggested that vitamin E protected cells from injury due to oxygen free radicals. PMID- 1630436 TI - [Histopathological findings in rectal carcinomas undergoing preoperative irradiation combined with chemotherapy]. AB - To evaluate the utility of preoperative irradiation (42.6 Gy) for rectal cancer, we examined histological specimens of surgically resected tumors, which were treated with (36 cases) or without (39 cases) preoperative irradiation. On the basis of the histological findings, irradiated cases were classified into non effective group (17 cases) and effective group (19 cases). According to quantitative analysis, cancer gland ratio (CGR) was 31.3% in non-irradiated group, 16.6% in non-effective group and 3.6% in effective group, while fibrosis ratio was 19.9%, 34.4% and 38.6%, respectively. The radiotherapy significantly reduced cancer gland and induced fibrosis. Influencing factors of recurrence in rectal cancer, such as depth of invasion, ew, vessel invasion (ly, v) and lymph node involvements were improved in the irradiated group, especially in effective cases, as compared with the non-irradiated group. In conclusion, preoperative irradiation therapy was thought to contribute to control of local recurrence and result in improvement of survival rate by decreasing several risk factors. PMID- 1630437 TI - [Correlation of DNA index and BrdU labeling index with clinicopathological factors in colorectal carcinoma]. AB - We studied the usefulness of the DNA index (DI) and bromodeoxyuridine (BrdU) labeling index (BLI) using fresh material from 71 patients with colorectal carcinoma. We compared the DI and BLI of the biopsy specimens with those of the resected specimens from 17 patients. These DI and BLI values were evaluated by flow cytometry. Neither DNA ploidy nor DI was correlated with other clinicopathologic factors. Intratumoral DI heterogeneity (DIH) was found in 33.8% (24/71) of tumors. Lymph node metastases were observed more often in cases with DIH than without DIH. The incidence of DIH was correlated with histologic stage. BLIs were higher in well-differentiated adenocarcinoma than in moderately and poorly differentiated adenocarcinoma. BLIs were not correlated with histologic stage. A significant correlation was observed between DI and BLI (r = 0.47, p less than 0.001). In cases without DIH, there was a good correlation between the DI values of the biopsy and resected specimens (r = 0.99, p less than 0.001). A significant correlation was also found between the BLI values of the two types of specimens (r = 0.69, p = 0.002). These results suggested that 4 biopsy specimens were adequate to estimate DI and BLI by FCM, and that DI and BLI values determined by FCM could facilitate the design of treatment regimens for preoperative patients. PMID- 1630438 TI - [Experimental study of bacterial adherence to biliary tract in rabbits]. AB - Adherence to host tissues and cell surfaces is an early step in infections. However nothing has been reported about bacterial adherence in biliary infections. The following experiment was carried out in rabbits with Escherichia coli isolated from the bile of a patient with acute suppurative cholangitis. Adhesion was observed by scanning electron microscopy. First, with cholecystic mucosa of normal, jaundice, acid (mucosa was injured with 0.1 N hydrochloric acid) and stone groups (stones were inserted into the gallbladder), bacterial adhesion as a virulence factor was examined in vitro. Second, in a cholangitis model the role of bacterial adherence to the bile duct in the development of localized biliary infection was examined in vivo. RESULT: (1) As compared to the normal, jaundice and stone groups, the number of adhering bacteria was remarkably increased in the acid group. The mucosa of the former groups was relatively intact, but that of the latter was remarkably destroyed. (2) In the cholangitis model, the number of bacteria adhered to the bile duct was negatively correlated with that of bacteria isolated from blood. These results suggest that bacterial adherence to the biliary tract is an important virulence factor, but not in the development from localized cholangitis to sepsis. PMID- 1630439 TI - [Long-term clinical results after aortic valve replacement with mechanical heart valves and mitral valve replacement with porcine valves]. AB - Long-term clinical results of aortic valve replacement (AVR) with mechanical heart valves and mitral valve replacement (MVR) with porcine valves were analysed. Sixty-three patients received isolated AVR and 48 received isolated MVR. Sixty-eight patients with MVR including double or triple valve replacement were also added in order to evaluate the primary tissue failure (PTF). The patients with operative deaths were excluded. Survival rate at 11 years in AVR was 68 +/- 10% and 67 +/- 15% in MVR without statistical difference. At 11 years, 76 +/- 8% of the patients in AVR were free from valve-related complications in contrast with the poor result of 34 +/- 31% in MVR (p less than 0.01). Main cause of this poor result in MVR was PTF as indicated in following event free rates; 83 +/- 9% at 7 years, 61 +/- 25% at 10 years and 49 +/- 31% at 13 years. There was no statistical difference between patients of above 50 years and below 49 years in PTF. Valve-related death event free was 93 +/- 5% in AVR and 86 +/- 11% in MVR at 11 years (not significant), however, there was statistical difference in re operation event free rate as 94 +/- 5% in AVR and 76 +/- 11% in MVR at 11 years (p less than 0.001). These results suggest that the use of porcine valves in mitral position is confined to the selected patients. PMID- 1630440 TI - [Efficacy of magnetic resonance imaging in treatment of neuroblastoma]. AB - Magnetic resonance imaging (MRI) was performed in 36 children with neuroblastoma at Chiba University from 1984 through 1989, and 29 patients of them were discussed about efficacy of MRI in treatment of neuroblastoma in this paper and the results were as follows. 1) MRI was difficult to differentiate tumor from normal kidney in the image intensity and was more efficient in determining the relationship of tumor to liver and to vascular structures. 2) MRI was better than CT in detecting the size and extent of tumor mass and in identifying lymph node spread using multiple planes. 3) MRI was more efficient than CT in defining displacement and encasement of renal vessels by tumor. It was useful to predict to reserve kidney before surgery. 4) MRI was useful to monitor tumor response to combined modalities of therapy. A favorable response was seen as a change in the image intensity in bone marrow metastases of neuroblastoma. PMID- 1630441 TI - [A case of endometrioid carcinoma arising from endometriosis of the rectum]. AB - A very rare case with rectal endometriosis heterotopic transformed into carcinoma is reported. A 44-year-old female patient underwent colostomy due to ileus. Postoperative examinations revealed submucosal tumors all around the rectum. Low anterior resection and the closure of the colostomy were performed. Thickening in the muscular layer and serosa were observed in the resected specimen, but the mucosal surface was maintained. Histopathological observation revealed glands of the endometrium and connective fibers with glandular adenocarcinoma in the periphery. Transformation of the benign endometrial tissues into carcinoma and squamous metaplasia were observed. A diagnosis of endometrial carcinoma in the rectum was made. PMID- 1630443 TI - [Trial on MR portal blood flow measurement with phase contrast technique: preliminary report]. PMID- 1630442 TI - [A case of anaplastic carcinoma of the mediastinal goiter]. AB - We reported a case of anaplastic carcinoma of mediastinal goiter. The initial symptom was hoarseness, and thyroid scintigram and venogram revealed mediastinal thyroid malignant tumor, although cervical tumor could not be palpated. Operation was performed with median sternotomy. The size of the tumor was 8 x 6 x 3cm. Histological examination showed papillary adenocarcinoma of left lower pole of the thyroid gland which was transformed into anaplastic carcinoma and extended to the mediastinal cavity. Anaplastic carcinoma of mediastinal goiter is very rare, and our case showed anaplastic transformation from papillary adenocarcinoma. PMID- 1630444 TI - [Nuclear P53 immunoreactivity associated with poor prognosis of gastric cancer: preliminary report]. PMID- 1630445 TI - [Tracheal reconstruction of extensive circumferential defects using cadaveric tracheal allograft: preliminary report]. PMID- 1630446 TI - [Enhancement of cytotoxicity in the regional lymph node cells by local injection of carbon particles adsorbing aclacinomycin a: preliminary report]. PMID- 1630447 TI - Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins. AB - Alpha interferon stimulates transcription by converting the positive transcriptional regulator ISGF3 from a latent to an active form. This receptor mediated event occurs in the cytoplasm, with subsequent translocation of the activated factor to the nucleus. ISGF3 has two components, termed ISGF3 alpha and ISGF3 gamma. ISGF3 gamma serves as the DNA recognition subunit, while ISGF3 alpha, which appears to consist of three polypeptides, is a target for alpha interferon signaling and serves as a regulatory component whose activation is required to form ISGF3. ISGF3 gamma DNA-binding activity was identified as a 48 kDa polypeptide, and partial amino acid sequence has allowed isolation of cDNA clones. ISGF3 gamma translated in vitro from recombinant clones bound DNA with a specificity indistinguishable from that of ISGF3 gamma purified from HeLa cells. Sequencing of ISGF3 gamma cDNA clones revealed significant similarity to the interferon regulatory factor (IRF) family of DNA binding proteins in the amino terminal 117 residues of ISGF3 gamma. The other IRF family proteins bind DNA with a specificity related to but distinct from that of ISGF3 gamma. We note sequence similarities between the related regions of IRF family proteins and the imperfect tryptophan repeats which constitute the DNA-binding domain of the c-myb oncoprotein. These sequence similarities suggest that ISGF3 gamma and IRF proteins and the c-myb oncoprotein use a common structural motif for DNA recognition. Recombinant ISGF3 gamma, like the natural protein, interacted with HeLa cell ISGF3 alpha to form the mature ISGF3 DNA-binding complex. We suggest that other IRF family members may participate in signaling pathways by interacting with as yet unidentified regulatory subunits analogous to ISGF3 alpha. PMID- 1630448 TI - Inducible processing of interferon regulatory factor-2. AB - PRDI-BFc and PRDI-BFi are proteins that bind specifically to a regulatory element required for virus induction of the human beta interferon (IFN-beta). PRDI-BFc is a constitutive binding activity, while the PRDI-BFi binding activity is observed only after cells are treated with inducers such as virus or poly(I).poly(C) plus cycloheximide or in some cells by cycloheximide alone. In this paper we report that PRDI-BFc is interferon regulatory factor-2 (IRF-2), a known transcriptional repressor. In addition, we find that PRDI-BFi is a truncated form of IRF-2, lacking approximately 185 C-terminal amino acids. Thus, PRDI-BFi appears to be generated by inducible proteolysis. Although the affinity of PRDI-BFc/IRF-2 for the IFN-beta promoter does not appear to be affected by the removal of C-terminal amino acids, the ability of PRDI-BFi to function as a repressor in cotransfection experiments is significantly less than that of intact IRF-2. Studies have shown that IRF-2 can block the activity of the transcriptional activator IRF-1, which also binds specifically to the IFN-beta gene promoter. Thus, the inducible proteolysis of IRF-2 may be involved in the regulation of the IFN-beta gene or of other genes in which the ratio of IRF-1 to IRF-2 can affect the level of transcription. PMID- 1630449 TI - RCC1, a regulator of mitosis, is essential for DNA replication. AB - Temperature-sensitive mutants in the RCC1 gene of BHK cells fail to maintain a correct temporal order of the cell cycle and will prematurely condense their chromosomes and enter mitosis at the restrictive temperature without having completed S phase. We have used Xenopus egg extracts to investigate the role that RCC1 plays in interphase nuclear functions and how this role might contribute to the known phenotype of temperature-sensitive RCC1 mutants. By immunodepleting RCC1 protein from egg extracts, we find that it is required for neither chromatin decondensation nor nuclear formation but that it is absolutely required for the replication of added sperm chromatin DNA. Our results further suggest that RCC1 does not participate enzymatically in replication but may be part of a structural complex which is required for the formation or maintenance of the replication machinery. By disrupting the replication complex, the loss of RCC1 might lead directly to disruption of the regulatory system which prevents the initiation of mitosis before the completion of DNA replication. PMID- 1630450 TI - Can, a putative oncogene associated with myeloid leukemogenesis, may be activated by fusion of its 3' half to different genes: characterization of the set gene. AB - The translocation (6;9)(p23;q34) in acute nonlymphocytic leukemia results in the formation of a highly consistent dek-can fusion gene. Translocation breakpoints invariably occur in single introns of dek and can, which were named icb-6 and icb 9, respectively. In a case of acute undifferentiated leukemia, a breakpoint was detected in icb-9 of can, whereas no breakpoint could be detected in dek. Genomic and cDNA cloning showed that instead of dek, a different gene was fused to can, which was named set. set encodes transcripts of 2.0 and 2.7 kb that result from the use of alternative polyadenylation sites. Both transcripts contain the open reading frame for a putative SET protein with a predicted molecular mass of 32 kDa. The set-can fusion gene is transcribed into a 5-kb transcript that contains a single open reading frame predicting a 155-kDa chimeric SET-CAN protein. The SET sequence shows homology with the yeast nucleosome assembly protein NAP-I. The only common sequence motif of SET and DEK proteins is an acidic region. SET has a long acidic tail, of which a large part is present in the predicted SET-CAN fusion protein. The set gene is located on chromosome 9q34, centromeric of c-abl. Since a dek-can fusion gene is present in t(6;9) acute myeloid leukemia and a set can fusion gene was found in a case of acute undifferentiated leukemia, we assume that can may function as an oncogene activated by fusion of its 3' part to dek, set, or perhaps other genes. PMID- 1630451 TI - Regulation of the junB gene by v-src. AB - The proteins encoded by cellular and viral src genes are believed to be involved in the transmission of mitogenic signals, the nuclear recipients of which are largely unknown. In this work, we report that four different v-src-transformed cell lines from three different species possess elevated levels of junB transcripts. Transient expression of junB promoter-chloramphenicol acetyltransferase constructs in NIH 3T3 cells was used to demonstrate that the increase in junB transcripts was specifically associated with v-src expression and could not be recapitulated with a c-src, v-H-ras, or v-raf expression vector. Deletion mutants were used to localize the v-src-responsive region in the junB promoter to a 121-nucleotide region encompassing the CCAAT and TATAA elements. This region is distinct from one in the 5' untranslated region of the junB gene which is required to maintain its high-level basal expression. Point mutagenesis of the junB TATAA box completely abolished v-src responsiveness, suggesting that proteins which bind to this element are modified by src transformation. Several v src and c-src mutants were used to demonstrate that elevated tyrosine kinase activity of src proteins is required for the observed effects on junB expression. Finally, homology between the TATAA box regions of junB and the unrelated but src responsive gene 9E3/CEF-4 suggests that modulation of gene activity through proteins which bind to this region may be a recurrent, although not exclusive, theme in src transforming action. Our results suggest that src proteins may modulate some nuclear effectors through pathways not involving cellular ras or raf gene products. PMID- 1630452 TI - Extrachromosomal homologous DNA recombination in plant cells is fast and is not affected by CpG methylation. AB - Using a sensitive transient assay, we investigated extrachromosomal homologous DNA recombination (ECR) in plant cells. As the plant genome is highly C methylated, we addressed the question of whether CpG methylation has an influence on DNA recombination efficiencies. Whereas the expression level of the fully CpG methylated DNA molecules was reduced drastically, we found no significant changes in ECR efficiencies between two partly CpG-methylated plasmids or between one fully CpG-methylated and one nonmethylated plasmid. Using a modified polymerase chain reaction analysis, we were able to detect recombination between two fully CpG-methylated plasmids. Furthermore, we characterized the kinetics of the ECR reaction. Cotransfection of plasmids carrying truncated copies of the beta glucuronidase (GUS) gene resulted in enzyme activity with a delay of only half an hour compared with that of the plasmid carrying the functional marker gene. This indicates that the ECR reaction itself requires no more than 30 min. By polymerase chain reaction, we were able to detect the recombined GUS gene as early as 2 h after transfection. This result and the time course of the transient GUS activity indicate that ECR occurs mainly early after transfection. The biological significance of this finding is discussed, and properties of ECR and intrachromosomal recombination are compared. PMID- 1630453 TI - The coat protein of the yeast double-stranded RNA virus L-A attaches covalently to the cap structure of eukaryotic mRNA. AB - The eukaryotic mRNA 5' cap structure m7GpppX (where X is any nucleotide) interacts with a number of cellular proteins. Several of these proteins were studied in mammalian, yeast, and drosophila cells and found to be involved in translation initiation. Here we describe a novel cap-binding protein, the coat protein of L-A, a double-stranded RNA virus that is persistently maintained in many Saccharomyces cerevisiae strains. The results also suggest that the coat protein of a related double-stranded RNA virus (L-BC) is likewise a cap-binding protein. Strikingly, in contrast to the cellular cap-binding proteins, the interaction between the L-A virus coat protein and the cap structure is through a covalent bond. PMID- 1630454 TI - Characterization of cis-acting elements regulating transcription from the promoter of a constitutively active rice actin gene. AB - The promoter of the constitutively expressed rice (Oryza sativa) actin 1 gene (Act1) is highly active in transformed rice plants (W. Zhang, D. McElroy, and R. Wu, Plant Cell 3:1150-1160, 1991). A region 834 bp upstream of the Act1 transcription initiation site contains all the regulatory elements necessary for maximal gene expression in transformed rice protoplasts (D. McElroy, W. Zhang, J. Cao, and R. Wu, Plant Cell 2:163-171, 1990). We have constructed a series of Act1 promoter deletions fused to a bacterial beta-glucuronidase reporter sequence (Gus). Transient expression assays in transformed rice protoplasts, as well as transformed maize cells and tissues, identified two distinct cis-acting regulatory elements in the Act1 promoter. A 38-bp poly(dA-dT) region was found to be a positive regulator of Act1 promoter activity. Deletion of the poly(dA-dT) element lowered Gus expression by at least threefold compared with expression produced by the full-length Act1 promoter. By gel retardation and footprinting, we identified a ubiquitous rice protein which specifically recognizes this poly(dA-dT) element in the constitutively active Act1 promoter. A CCCAA pentamer repeat-containing region was found to be a negative regulator of the Act1 promoter in transformed rice protoplasts. Transient expression assays in different maize cells and tissues with use of the Act1 deletion constructs suggested that the CCCAA pentamer repeat region functions in a complex tissue specific manner. A CCCAA-binding protein was detected only in root extracts. PMID- 1630455 TI - The functional importance of a cap site-proximal region of the human prointerleukin 1 beta gene is defined by viral protein trans-activation. AB - Prointerleukin 1 beta (IL-1 beta) is a cytokine that mediates a broad range of biological activities. Genomic sequences that regulate IL-1 beta transcription include both inducible regulatory elements located more than 2,700 bp upstream of the transcriptional start site (cap site) and proximal elements located near the TATA box of this gene. In this study, we focused on the identification and characterization of trans-acting nuclear regulatory proteins that bind to the cap site-proximal region of the human IL-1 beta gene. We identified a protein, termed NFIL-1 beta A (NF beta A), that binds to a highly conserved 12-bp DNA sequence ( 49 to -38) located upstream of the TATA box motif in both the human and murine IL 1 beta genes. The IL-1 alpha gene, which lacks a TATA motif, does not possess an NF beta A-binding sequence within the promoter region, suggesting that NF beta A may selectively regulate IL-1 beta expression. Using electrophoretic mobility shift assays, we identified several distinct DNA-protein complexes that are expressed in a cell-type-specific manner. In monocytic cell lines, the relative abundance of these complexes varies rapidly following stimulation of the cells with phorbol esters or lipopolysaccharide. UV cross-linking analysis identified two distinct DNA-binding polypeptides that comprise distinct complexes. The functional role of NF beta A was assessed in transient transfection assays. These data indicate that NF beta A is required for both basal and inducible promoter activity in monocytic cells. Furthermore, the human cytomegalovirus immediate early 1 gene product requires the presence of NF beta A in order to trans activate the proximal IL-1 beta promoter in a monocytic cell line. We propose that NF beta A is a factor that mediates either direct or indirect activation by the immediate-early 1 gene product. The proximity of this essential factor to the TATA motif suggests a possible role in transcriptional initiation. PMID- 1630456 TI - Two species of human CRK cDNA encode proteins with distinct biological activities. AB - Two distinct human CRK cDNAs, designated CRK-I and CRK-II, were isolated from human embryonic lung cells by polymerase chain reaction and by screening of a human placenta cDNA library, respectively. CRK-I differed from CRK-II in that it lacked a 170-nucleotide sequence, suggesting that CRK-I and CRK-II were the products of alternative splicing. The amino acid sequences deduced from these two cDNAs differed in the carboxyl termini and contained one SH2 and either one or two SH3 domains. RNAse protection analysis demonstrated both CRK-I and CRK-II mRNAs in various human cells. Three CRK proteins, of 42, 40, and 28 kDa, were identified in human embryonic lung cells by means of antibodies against the SH2 region and the SH3 region of the bacterially expressed CRK-I protein. Transient expression of CRK-I and CRK-II cDNAs in COS7 cells showed that the former encoded the 28-kDa protein and the latter encoded the 40- and 42-kDa proteins. All human cell lines so far examined expressed the 40-kDa protein; however, expression of the 28- and the 42-kDa proteins was variable. In a comparison of the biological activity of the two human CRK proteins, both proteins were stably expressed in rat 3Y1 cells. All cell lines expressing CRK-I protein showed altered morphology, proliferated in soft agar, and grew as massive tumors in nude mice. Although CRK II-expressing cells showed a slight morphologic change, they did not make colonies in soft agar or grow in nude mice. These results demonstrate that the two species of human CRK cDNA encode proteins which differ in their biological activities. PMID- 1630457 TI - The gene for a novel human lamin maps at a highly transcribed locus of chromosome 19 which replicates at the onset of S-phase. AB - A previously described human DNA fragment which is replicated early in S-phase of HL-60 cell DNA (C. Tribioli, G. Biamonti, M. Giacca, M. Colonna, S. Riva, and A. Falaschi, Nucleic Acids Res. 15:10211-10232, 1987) was used to screen a genomic library in lambda Ch28. A clone which contained a 13.7-kb insert (L30E) found to code for several transcripts was isolated. The transcription of L30E DNA exhibited a complex pattern and a tissue-specific and proliferation-dependent type of regulation. The data were consistent with two tandemly arranged transcription units, the 3' end of one separated from the 5' end of the other by a sequence of about 600 bp containing an active promoter. The isolation and sequencing of L30E-specific cDNAs permitted identification of two genes, one of which encoded a B-type human lamin (analogous to mouse lamin B2). L30E DNA was mapped by in situ hybridization at the G-negative subtelomeric band p13.3 of chromosome 19. Interestingly, in synchronized HL-60 cells, L30E DNA is replicated in the first minute of S-phase. Replication of the lamin gene early in S-phase may reflect a coupling between early replication and transcription of genes for S phase-specific proteins such as lamins. PMID- 1630458 TI - Oncoprotein-mediated signalling cascade stimulates c-Jun activity by phosphorylation of serines 63 and 73. AB - In resting cells, c-Jun is phosphorylated on five sites. Three of these sites reside next to its DNA binding domain and negatively regulate DNA binding. In response to expression of oncogenic Ha-Ras, phosphorylation of these sites decreases, while phosphorylation of two other sites within c-Jun's activation domain is greatly enhanced. Phosphorylation of these residues, serines 63 and 73, stimulates the transactivation function of c-Jun and is required for oncogenic cooperation with Ha-Ras. We now show that the same changes in c-Jun phosphorylation are elicited by a variety of transforming oncoproteins with distinct biochemical activities. These oncoproteins, v-Sis, v-Src, Ha-Ras, and Raf-1, participate in a signal transduction pathway that leads to increased phosphorylation of serines 63 and 73 on c-Jun. While oncogenic Ha-Ras is a constitutive stimulator of c-Jun activity and phosphorylation, the normal c-Ha Ras protein is a serum-dependent modulator of c-Jun's activity. c-Jun is therefore a downstream target for a phosphorylation cascade involved in cell proliferation and transformation. PMID- 1630459 TI - Regulation and expression of a growth arrest-specific gene (gas5) during growth, differentiation, and development. AB - The growth arrest-specific gas5 gene was isolated from mouse genomic DNA and structurally characterized. The transcriptional unit is divided into 12 exons that span around 7 kb. An alternative splicing mechanism gives rise to two mature mRNAs which contain either 11 or 12 exons, and both are found in the cytoplasm of growth-arrested cells. In vivo, the gas5 gene is ubiquitously expressed in mouse tissues during development and adult life. In Friend leukemia and NIH 3T3 cells, the levels of gas5 gene mRNA were high in saturation density-arrested cells and almost undetectable in actively growing cells. Run-on experiments indicated that the gas5 gene is transcribed at the same level in both growing and arrested cells. On the other hand, in dimethyl sulfoxide-induced differentiating cells a sharp decrease in the rate of transcription was observed shortly before the cells reached the postmitotic stage. These results indicate that in density-arrested cells accumulation of gas5 mRNA is controlled at the posttranscriptional level while in differentiating cells expression is regulated transcriptionally. PMID- 1630460 TI - Regulated degradation of ornithine decarboxylase requires interaction with the polyamine-inducible protein antizyme. AB - Intracellular degradation of vertebrate ornithine decarboxylase (ODC) is accelerated by polyamines, the products of the pathway controlled by ODC. Antizyme, a reversible, tightly binding protein inhibitor of ODC activity, is believed to be involved in this process. Mouse and Trypanosoma brucei ODCs are structurally similar, but the trypanosome enzyme, unlike that of the mouse, is not regulated by intracellular polyamines when expressed in hamster cells (L. Ghoda, D. Sidney, M. Macrae, and P. Coffino, Mol. Cell. Biol. 12:2178-2185, 1992). We found that mouse ODC interacts with antizyme in vitro but trypanosome ODC does not. To localize the region necessary for binding, we made a series of enzymatically active chimeric mouse-trypanosome ODCs and tested them for antizyme interaction. Replacing residues 117 to 140 within the 461-amino-acid mouse ODC sequence with the equivalent region of trypanosome ODC disrupted both antizyme binding and in vivo regulation. Formation of an antizyme-ODC complex is therefore required for regulated degradation. PMID- 1630461 TI - The N-terminal 96 residues of MCM1, a regulator of cell type-specific genes in Saccharomyces cerevisiae, are sufficient for DNA binding, transcription activation, and interaction with alpha 1. AB - MCM1 performs several functions necessary for its role in regulating cell type specific gene expression in the yeast Saccharomyces cerevisiae: DNA binding, transcription activation, and interaction with coregulatory proteins such as alpha 1. We analyzed a set of MCM1 deletion derivatives using in vivo reporter gene assays and in vitro DNA-binding studies to determine which regions of MCM1 are important for its various activities. We also analyzed a set of LexA-MCM1 hybrids to examine the ability of different segments of MCM1 to activate transcription independent of MCM1's DNA-binding function. The first third of MCM1 [MCM1(1-96)], which includes an 80-residue segment homologous to the mammalian serum response factor, was sufficient for high-affinity DNA binding, for activation of reporter gene expression, and for interaction with alpha 1 in vitro and in vivo. However, the ability of MCM1(1-96) to activate transcription and to interact with alpha 1 was somewhat reduced compared with wild-type MCM1 [MCM1(1 286)]. Optimal interaction with alpha 1 required residues 99 to 117, in which 18 of 19 amino acids are acidic in character. Optimal transcription activation required a segment from residues 188 to 286, in which 50% of the amino acids are glutamine. Deletion of this segment from MCM1 reduced expression of reporter genes by about twofold. Moreover, LexA-MCM1 hybrids containing this segment were able to activate expression of reporter genes that rely on LexA binding sites as potential upstream activation sequences. Thus, glutamine-rich regions may contribute to the activation function of yeast transcription activators, as has been suggested for glutamine-rich mammalian proteins such as Sp1. PMID- 1630462 TI - The yeast alpha 1 and MCM1 proteins bind a single strand of their duplex DNA recognition site. AB - The yeast cell type regulator alpha 1 cooperates with a constitutive factor, MCM1 protein, to recognize the promoter and activate transcription of several alpha specific genes. I show here that the alpha 1 and MCM1 proteins bind specifically to one of the two strands of their recognition sequence. This single-strand binding activity shares several characteristics with the duplex-binding properties of these proteins: (i) the MCM1 protein binds alone to single-stranded and duplex sequences of both the alpha-specific (P'Q) and a-specific (P) binding sites; (ii) the alpha 1 protein requires both the MCM1 protein and the Q sequence to bind either single-stranded or duplex DNA; (iii) the alpha 1 protein stimulates binding of the MCM1 protein to both single-stranded and duplex DNAs; and (iv) the affinities of the proteins for single-stranded and duplex DNAs are comparable. PMID- 1630464 TI - Effects of mutation position on frequency of marker rescue by homologous recombination. AB - Homologous recombination between transferred and chromosomal DNA can be used for mapping mutations by marker rescue, i.e., by identifying which segment of wild type DNA can recombine with the mutant chromosomal gene and restore normal function. In order to define how much the fragments should overlap each other for reliable mapping, we have measured how the frequency of marker rescue is affected by the position of the chromosomal mutation relative to the ends of the transferred DNA fragments. For this purpose, we used several DNA fragments to effect marker rescue in two mutant hybridomas which bear mutations 673 bp apart in the exons encoding the second and third constant region domains of the immunoglobulin mu heavy chain. The frequency of marker rescue decreased greatly when the mutation was located near one of the ends of the fragments, the results indicating that fragments should be designed to overlap by at least several hundred base pairs. Possible explanations for this "end effect" are considered. PMID- 1630465 TI - Infection control. Wound management. PMID- 1630463 TI - Occupancy of upstream regulatory sites in vivo coincides with major histocompatibility complex class I gene expression in mouse tissues. AB - The major histocompatibility complex (MHC) class I HLA-B7 transgene carrying a 660-bp upstream sequence is expressed in the mouse with tissue specificity that parallels that of the expression of endogenous mouse MHC class I (H-2) genes. We have performed in vivo genomic footprinting for the HLA-B7 transgene and the endogenous H-2Kb gene. We show that the upstream region of both the transgene and the endogenous gene was extensively occupied in spleen tissue, where these genes are expressed at high levels. In contrast, no occupancy was detected in brain tissue, where expression of these genes is virtually absent. Sites exhibiting in vivo protection correspond to cis elements previously shown to bind to nuclear factors in vitro, including the constitutive enhancer region I and the interferon response element. The strongest tissue-specific protection was detected at site alpha, located downstream from the interferon response element. Site alpha bound a constitutively expressed nuclear factor(s) in vitro that exhibited an overlapping specificity which may involve a nuclear hormone receptor, RXR, and an AP-1-related factor. Site alpha was functional in vivo, as it enhanced MHC class I transcription in lymphocytes. These results show that the tissue-specific occupancy of the MHC class I regulatory sequences in vivo correlates with their expression and suggest that in vivo occupancy is controlled by a mechanism other than the mere presence of factors capable of binding to these sites. Our results suggest that a sequence present in the 660-bp upstream region in a human leukocyte antigen gene directs tissue-specific occupancy of MHC class I genes in vivo, independently of their position and copy number, illustrating a potential advantage of using a transgene for delimitation of the sequence requirement for in vivo occupancy. PMID- 1630466 TI - Infection control. Eusol--(E) useful or (e) useless? PMID- 1630467 TI - Infection control. Blood-borne pathogens: safety for the healthcare worker. PMID- 1630468 TI - Infection control. The do's and don'ts of antiseptics. PMID- 1630469 TI - Infection control. Nursing management of a patient with hepatitis A and B. AB - The Infection Control precautions for hepatitis B are those of "Blood and Body Fluid Precautions" and those of "Universal Precautions". Gloves, preferably latex, are worn when there is to be contact with blood and body fluid. Goggles/masks are worn when there is a danger of splashing or aerosol of blood contaminated secretions. A plastic apron, or water repellant gown, may be indicated if there is a danger of splashing. Hand washing before and after contact with blood and body fluid, even if gloves are worn. Specimens are treated as biohazard. Refuse and linen are treated as infectious. It is important to establish if the patient is in the acute phase, a carrier, or not. Education of the patient about the disease, is very important, especially in the carrier. This poses a problem when there is a language barrier. This is a sensitive subject and must be handled tactfully, especially if the mode of transmission was sexual. Safe sex must be discussed. The partner, and the newborn baby must be assessed and immunised. The transmission of hepatitis A is mainly faeco-oral, and the infection control measures those called "Enteric Precautions", or blood and body fluid precautions. These include the wearing of latex gloves when handling faeces, urine, saliva, and blood. Handwashing is essential. The patient has his own bedpan, urinal, crockery and cutlery. Isolation is continued for the first two weeks of the illness, and one week after the onset of jaundice. The Infection Control management for hepatitis A is slightly different to that of hepatitis B, C, and Non-A Non-B. PMID- 1630470 TI - Infection control. Management of sharps injuries. PMID- 1630472 TI - Infection control. Infection control in a trauma unit. PMID- 1630471 TI - Infection control. The re-use of single-use medical devices. PMID- 1630473 TI - New AIDS safeguard available--and it is a must. PMID- 1630474 TI - Self-destructing syringes to combat AIDS. PMID- 1630475 TI - Al Gore's future. PMID- 1630476 TI - Patents for genomes? PMID- 1630477 TI - Audit faults US national labs. PMID- 1630478 TI - US drops Imanishi-Kari investigation; Baltimore withdraws Cell retraction. PMID- 1630479 TI - Wall Street remains bearish on value of genome project. PMID- 1630480 TI - Delaney's revenge: court rejects US approach to assessing cancer risks in processed foods. PMID- 1630481 TI - Multiplicity of migrants. AB - An informed debate on the manner in which legislation on migration from food packaging is introduced is badly needed. Until then, scientific resources are being needlessly wasted. PMID- 1630483 TI - Cost of brain disorders. PMID- 1630482 TI - Cost of brain disorders. PMID- 1630484 TI - Well-being and productivity. PMID- 1630485 TI - How to publish the unpalatable? PMID- 1630486 TI - Palaeontology. Wandering across time. PMID- 1630487 TI - Bear conservation genetics. PMID- 1630488 TI - Molecular replication. AB - Simple replicating molecules are likely to have played a critical role in the origin of life. Recent experiments show that non-enzymatic replication is conceivable in a wide range of synthetic chemical systems. The challenge now facing these studies is how to develop information-coding systems from simple prebiotic precursors. PMID- 1630489 TI - Atomic structure and chemistry of human serum albumin. AB - The three-dimensional structure of human serum albumin has been determined crystallographically to a resolution of 2.8 A. It comprises three homologous domains that assemble to form a heart-shaped molecule. Each domain is a product of two subdomains that possess common structural motifs. The principal regions of ligand binding to human serum albumin are located in hydrophobic cavities in subdomains IIA and IIIA, which exhibit similar chemistry. The structure explains numerous physical phenomena and should provide insight into future pharmacokinetic and genetically engineered therapeutic applications of serum albumin. PMID- 1630490 TI - Post-Jurassic mammal-like reptile from the Palaeocene. AB - Mammal-like reptiles of the order Therapsida document the emergence of mammals from more primitive synapsids and are of unique zoological and palaeontological interest on that account. Therapsids, first appearing in the Early Permian, were thought to become extinct in the Middle Jurassic, soon after the Late Triassic origin of mammals. Here, however, we report the discovery of a therapsid from the late Palaeocene, 100 million years younger than the youngest previous occurrence of the order. This discovery nearly doubles the stratigraphic range of therapsids and furnishes their first record from the Cenozoic. The documenting fossils, an incomplete dentary containing three teeth, and four isolated teeth from other, conspecific individuals (Fig. 1), are from the Paskapoo Formation, at Cochrane, Alberta, Canada, from beds yielding a diverse mammalian fauna of early Tiffanian age. These specimens are catalogued in the collections of the University of Alberta Laboratory for Vertebrate Paleontology (UALVP) and provide the basis for a new taxon, as named and described below: (see text) PMID- 1630491 TI - TCP1 complex is a molecular chaperone in tubulin biogenesis. AB - A role in folding of newly translated proteins in the cytosol of eukaryotes has been proposed for t-complex polypeptide-1 (TCP1), although its molecular targets have not yet been identified. Tubulin is a major cytosolic protein whose assembly into microtubules is critical to many cellular processes. Although numerous studies have focused on the expression of tubulin, little is known about the processes whereby newly translated tubulin subunits acquire conformations that enable them to form alpha-beta-heterodimers. We examined the biogenesis of alpha- and beta-tubulin in rabbit reticulocyte lysate, and report here that newly translated tubulin subunits entered a 900K complex in a protease-sensitive conformation. Addition of Mg-ATP, but not nonhydrolysable analogues, released the tubulin subunits as assembly-competent protein with a conformation that was relatively protease-resistant. The 900K complex purified from reticulocyte lysate contained as its major constituent a 58K protein that cross-reacted with a monoclonal antiserum against mouse TCP1. We conclude that TCP1 functions as a cytosolic chaperone in the biogenesis of tubulin. PMID- 1630492 TI - T-complex polypeptide-1 is a subunit of a heteromeric particle in the eukaryotic cytosol. AB - The murine t-complex encodes t-complex polypeptide-1 (TCP1), which is constitutively expressed in almost all cells, and upregulated during spermatogenesis. Mammalian sequences have greater than 96% identity with each other, and greater than 60% identity with Drosophila melanogaster and yeast orthologues. TCP1 is essential in yeast, and is postulated to be the cytosolic mammalian equivalent of groEL. We report here that, in the native state, murine and human TCP1 is distributed throughout the cytosol as an 800K-950K hetero oligomeric particle in association with four to six unidentified proteins and two Hsp70 heat-shock proteins. Negative-stain electron microscopy indicates that the structure is two stacked rings, 12-16 nm in diameter. Therefore, despite similarities with the chaperonin 60 proteins, these data indicate that TCP1 is biochemically and structurally unique. We suggest that TCP1 may represent one of a family of molecules in the eukaryotic cytosol involved in protein folding and regulated in part by their heteromeric associations. PMID- 1630493 TI - Cytotoxic T-lymphocyte activation involves a cascade of signalling and adhesion events. AB - In addition to the antigen-specific T-cell receptor (TCR), T cells bear an array of 'accessory' molecules that can contribute to stable adhesion to the antigen bearing cell and provide costimulatory signals. For several of these, T-cell adhesion to the ligand can be activated by TCR-dependent signalling (a signal from the TCR primes the coreceptor to bind to its ligand). It is unclear whether the individual coreceptors share common mechanisms of priming and cosignalling, and perhaps act in a redundant manner, or whether they act in a distinct way and contribute uniquely to the activation process. We report here the use of isolated alloantigen, class I proteins and fibronectin ligands to show that coreceptors on cytotoxic T lymphocytes are activated sequentially and deliver distinct biochemical signals on binding to their ligands. TCR engagement activates CD8 by a protein tyrosine kinase-dependent pathway, and CD8 then acts as a signal for initiation of polyphosphoinositide hydrolysis on binding to class I. In contrast, activated adhesion to fibronectin does not initiate polyphosphoinositide hydrolysis, but amplifies hydrolysis once it has been initiated. Thus, cytotoxic T-lymphocyte activation involves a TCR-initiated cascade of adhesion and signalling events leading to response. PMID- 1630494 TI - Superantigen implicated in dependence of HIV-1 replication in T cells on TCR V beta expression. AB - In the pathogenesis of AIDS it is not yet understood whether the small fraction of CD4+ T cells (approximately 1%) infected with the human immunodeficiency virus (HIV) are randomly targeted or not. Here we present evidence that human CD4 T cell lines expressing selected T-cell antigen receptor V beta gene products can all be infected in vitro with HIV-1, but give markedly different titres of HIV-1 virion production. For example, V beta 12 T-cell lines from several unrelated donors reproducibly yielded up to 100-fold more gag gene product (p24gag antigen) than V beta 6.7a lines. This is consistent with a superantigen effect, because the V beta selectivity was observed with several divergent HIV-1 isolates, was dependent on antigen-presenting cells and on major histocompatibility complex (MHC) class II but was not MHC class II-restricted. The in vivo significance of these findings is supported by the preferential stimulation of V beta 12+ T cells by freshly obtained irradiated antigen-presenting cells from some HIV-1 seropositive but not HIV-1-negative donors. Moreover, cells from patients positive for viral antigen (gp120) were enriched in the V beta 12 subpopulation. V beta 12+ T cells were not deleted in AIDS patients, however, raising the possibility that a variety of mechanisms contribute to T-cell depletion. Our results indicate that a superantigen targets a subpopulation of CD4+ cells for viral replication. PMID- 1630496 TI - [Gene probes and their use in microbiology]. AB - A gene probe (nucleic acid probe) is a single-stranded nucleic acid fragment that interacts with a complementary sequence of a target nucleic acid. The test is based upon the principles of nucleic acid hybridization reactions. Different assay formats (dot-blot, colony, whole-cell hybridizations) can be applied. Gene probes can be used for the rapid and specific identification of microorganisms. The phylogenetic identification and in situ detection of uncultured bacteria will be discussed. PMID- 1630497 TI - ECG and electrodermal response in Rana temporaria and Bufo bufo under the influence of autonomic-acting drugs. PMID- 1630495 TI - [Molecular biology and regulatory mechanisms of antibiotic production in Bacillus]. AB - Several species of the genus Bacillus produce linear and cyclic peptide antibiotics nonribosomally through multienzyme complexes by the so-called thiotemplate mechanism. Molecular genetic studies have shown that some peptide antibiotic biosynthesis genes are organized in operons and that they are expressed postexponentially under conditions that also activate the process of endospore formation in Bacillus. Furthermore, DNA-sequence analysis of some multifunctional peptide synthetase genes revealed that they contain a highly conserved and repeated domain structure. The same domain was also found to be conserved within a superfamily of peptide synthetases and adenylate-forming enzymes of diverse origins. Based on sequence homology and functional similarity I conclude that those enzymes bearing domain(s) represent a family of superenzymes which may have a common evolutionary origin. PMID- 1630498 TI - Compounds stimulating growth and multiplication in ciliates. Do also free-living cells release growth factors? PMID- 1630499 TI - U.S. health care dilemma. PMID- 1630500 TI - Cow dung cure. PMID- 1630501 TI - Environmental health. Should we be concerned? PMID- 1630502 TI - Environmental hazards and health risks. A public health viewpoint. PMID- 1630503 TI - Informed medical consent. PMID- 1630504 TI - Hazardous waste. A North Carolina dilemma. AB - North Carolina, along with the rest of the nation, faces a number of dilemmas regarding management of hazardous waste: 1. North Carolina businesses and industries generate a lot of hazardous waste, but the state lacks the capacity to manage it. For many, it has been acceptable to ship the waste to other states for treatment, storage, and disposal. Some of the receiving states have indicated that they are no longer willing to serve as the "dumping ground" for North Carolina. 2. North Carolina, along with the EPA, has identified a number of hazardous waste sites now listed on the NPL. However, the state was excluded from its regional agreement with Alabama, South Carolina, Kentucky, and Tennessee in January 1991, meaning that Superfund monies may be withdrawn and that cleanup won't be completed at these sites. 3. Every year the country produces at least 260 million tons of hazardous waste--more than one ton for every man, woman, and child. Those opposed to constructing hazardous waste treatment facilities charge that businesses and industries should reduce their hazardous waste to zero or near zero, and they charge that the state is not doing enough to encourage waste reduction. North Carolina's hazardous waste regulations already require programs to minimize the amounts of waste generated by industries, but for most industrial processes, it is impossible to reduce the generation of waste to zero. However, industries must continue to reduce their waste through source reduction and recycling. Hazardous waste and toxic materials do pose a risk to human health and the environment unless properly managed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630506 TI - Youth and alcohol. PMID- 1630507 TI - Health effects of indoor air pollution. PMID- 1630505 TI - Medical waste management. Federal perspective and North Carolina program. PMID- 1630508 TI - Radon in North Carolina. Does exposure create a significant health risk? PMID- 1630509 TI - What is the quality of water in North Carolina? PMID- 1630511 TI - Environmental risk assessment. Estimating risks contaminants pose to our health. PMID- 1630510 TI - Food safety. Lead, pesticides, antibiotics, hormones, and irradiation. PMID- 1630512 TI - [An arm in the wringer is not automatically lost]. PMID- 1630513 TI - [Methylene blue and pregnancy; revision of a calamity]. PMID- 1630514 TI - [Does a protein-poor diet delay the loss of kidney function?]. PMID- 1630515 TI - [Epilepsy and pregnancy]. PMID- 1630516 TI - [International reporting of adverse effects of drugs]. PMID- 1630517 TI - [The use of drugs for euthanasia and assisted suicide in family practice]. AB - An exploratory, descriptive, retrospective study was carried out concerning the use of means for euthanasia or assisted suicide, primarily regarding the period 1986-1989. Data were collected via an anonymous written inquiry among a random sample of family physicians in North Holland (n = 521) and family physicians in the rest of the Netherlands (n = 521). The inquiry contained among others questions about the last case they had encountered. In addition, police reports of euthanasia or assisted suicide administered by family physicians in North Holland (n = 263) were analysed. The response to the inquiry was 67%; (non respondents did not differ from respondents): 388 cases could be analysed. The use of euthanatics by family physicians in North Holland and those in the rest of the Netherlands was identical. More than 40 different euthanatics were used, most of them incidentally. The most frequently used (combination of) means were a benzodiazepine with a neuromuscular relaxant (23%), a barbiturate with a neuromuscular relaxant (20%), barbiturates (15%) and opioids (12%). Most euthanatics were given intravenously (61%, of which 5% by infusion), orally 21%, intramuscularly 12%, rectally 3% and subcutaneously 2%. The quantities applied varied greatly. The average length of time from the start of the procedure till decrease was 3.8 hours (less than or equal to 1 minute-72 hours). In 12% of the cases complications or unintended effects were reported. Comparison of inquiry and police reports showed some differences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630518 TI - [Revision consensus prevention and treatment decubitus]. AB - The text of the Consensus Meetings Prevention and Treatment of Decubitus (pressure sores; 1985 and 1986 respectively) was adapted to current insights into pathogenesis and treatment. This adaptation was important since the costs of the prevention and treatment of decubitus are enormous and decubitus tends to occur more often since the population is growing older. The so called anti-decubitus devices were grouped in 3 categories: 1. polyether foam mattresses, placed on top of the standard hospital mattresses (merely in prevention and in treatment of patients less than 85 kg), 2. polyether foam mattresses with or without special surface layout or simple alternating pressure air mattresses, replacing the standard hospital mattress (especially in patients greater than 85 kg) and 3. special beds and bed systems as low-air-loss beds and air-fluidized beds (only on strict indications such as thoracic operations and intensive treatments). The clinical manifestations of decubitus were classified in 4 stages: non-blanching erythema (1), blister (2), superficial decubitus (3) and deep decubitus (4). The existence of another form of pressure sores was identified: decubitus originating from operation or angiography tables, on which a deep necrosis develops, extending to form an abscess, erupting through the skin after 7-14 days. These ulcers are characterised by an impressive depth, usually to the underlying bones, but with vivid edges. The development of these sores is prevented in most cases by using a category 1 device on the tables mentioned.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630519 TI - [Public media and health care]. PMID- 1630520 TI - [Developments in the scientific field in surgery]. PMID- 1630521 TI - [Ultrasonography as initial imaging study can replace roentgen studies under certain conditions in suspected congenital hip dysplasia]. PMID- 1630522 TI - [Ultrasonography as initial imaging study can replace roentgen studies under certain conditions in suspected congenital hip dysplasia]. PMID- 1630523 TI - [Cerebrovascular accident]. PMID- 1630524 TI - [Should a patient with a stroke be hospitalized?]. PMID- 1630525 TI - [Should a patient with a stroke be hospitalized?]. PMID- 1630526 TI - [Traumatology in The Netherlands]. PMID- 1630527 TI - [Psychogenic aphonia; an easily and rapidly treatable conversion]. PMID- 1630528 TI - [High-density lipoproteins]. PMID- 1630529 TI - ['It is just a hernia']. PMID- 1630530 TI - [Medical activities under adverse conditions. The Medical Coordination Secretariat of the protestant (development aid) organizations in The Netherlands]. PMID- 1630531 TI - [Hemoglobinopathies in The Netherlands; is screening of foreign women advisable?]. PMID- 1630532 TI - [The treatment of familial hypercholesterolemia]. PMID- 1630533 TI - Salt output in relation to salt intake versus salt output alone: which is a better predictor of effective vascular volume? PMID- 1630534 TI - Plasma interleukin-6 levels in continuous ambulatory peritoneal dialysis and hemodialysis patients. AB - Plasma levels of interleukin-6 (IL-6), a cytokine known to be involved in lymphocyte activation and in inflammation, were studied in 10 normal volunteers, 21 continuous ambulatory peritoneal dialysis (CAPD) patients and 41 hemodialysis patients. Plasma IL-6 levels in hemodialysis patients were significantly higher than those in normal volunteers and CAPD patients (p less than 0.05). The means of plasma IL-6 concentrations before and after hemodialysis did not change significantly. While IL-6 in peritoneal dialysate was detectable in only 3 of the 21 CAPD patients without peritonitis, it was extremely high in 2 patients with bacterial peritonitis. IL-6 levels decreased as peritonitis subsided. PMID- 1630535 TI - Production of tumor necrosis factor-alpha in patients on hemodiafiltration. AB - The systemic production of tumor necrosis factor (TNF)-alpha was evaluated in uremic patients before and after hemodiafiltration (HDF) and paired filtration dialysis (PFD) and in the interdialytic period. Both HDF and PFD were performed using polysulfone dialyzers with either standard or ultrapure dialysis fluid. TNF alpha was quantitated by using a specific biological assay based on its cytotoxic effect on a TNF-sensitive human melanoma cell line SK-MEL-109. Postdialytic mean plasma TNF-alpha levels decreased, albeit not significantly, in regard to predialytic values. These results differ from those obtained in patients on HDF using other high-permeability membranes such as polymethylmethacrylate and polyacrylonitrile (AN 69) as recently described by us. Of interest, the adoption of ultrapure dialysis fluid resulted in a marked reduction in the interdialytic production of TNF-alpha. These results suggest that the enhanced production of TNF-alpha in patients dialyzed with high-permeability membranes is mainly dependent upon the bacteriological purity of dialysis fluid. PMID- 1630536 TI - Selenium in renal failure patients. AB - The selenium (Se) concentration in plasma, serum and whole blood was determined in 29 healthy persons, 19 nondialyzed patients with chronic renal disease (9 proteinuric but with otherwise normal renal function, 10 with chronic renal failure), and 10 dialyzed end-stage renal disease patients. No differences in Se concentrations of plasma, serum or whole blood were determined between patients and their matched controls. Total Se concentrations did not correlate with any of the Se carriers except with alpha 2-globulin. However, alpha 2-globulin concentrations were not different between patients and controls. Within the dialyzed patient group, Se concentrations did not change during dialysis. Se supplementation is not indicated in these patients. Within all groups analyzed, serum Se concentrations (12.7 +/- 2.5 micrograms/dl) were significantly (p less than 0.0001) lower than comparable plasma concentrations (15.3 +/- 3.9 micrograms/dl). These data suggest normal concentrations of blood Se in the groups of patients evaluated; and they are not Se-deficient. Serum Se concentrations cannot be equated with plasma values. PMID- 1630537 TI - Role of agglomeration in calcium oxalate monohydrate urolith development. AB - Formation of agglomerates of calcium oxalate monohydrate (COM) crystals on semi batch precipitation performed at conditions relevant to urolithiasis (37 degrees C, pH = 6, initial ratio [Ca]/[Ox] = 10), but without any specific admixture, was followed by both optical and electron microscopy. COM crystals formed on precipitation developed into large agglomerates consisting of intergrown crystals by a mechanism of primary agglomeration. Primary agglomeration of COM crystals represents an important mechanism of COM renal calculi growth. PMID- 1630538 TI - Deferoxamine test and PTH serum levels are useful not to recognize but to exclude aluminum-related bone disease. AB - The use of noninvasive diagnostic tools, like the deferoxamine (DFO) test and serum iPTH, to identify aluminum-related bone disease has proved to be inadequate due to false-negative cases; therefore, bone biopsy becomes a necessary diagnostic procedure. Our purpose was to verify whether these non-invasive parameters, appropriately used, may result valid in the identification of patients not at risk of Al toxicity, therefore restricting the need for histologic evaluation. We studied 68 hemodialyzed patients, aged 49.0 +/- 11.6 years, with a M/F ratio of 37/31 and a dialytic age of 85.0 +/- 47.0 months, by means of bone biopsy, DFO test and serum C-PTH. 19.1% of the cases had positive stainable Al and/or high bone Al content (greater than 60 mg/kg/dw) and could be intoxicated. To obtain the highest sensitivity, we selected the following limit values: the lower limit of increment so far proposed for DFO test positivity (greater than 150 micrograms/l) and a value capable of selecting patients with pathologic osteoclasia for C-PTH (greater than 15 ng/ml). With these limits, four different groups of patients were recognized: group A, DFO test positive and PTH high, n = 12; group B, DFO test positive and PTH low, n = 6; group C, DFO test negative and PTH high, n = 30; group D, DFO test negative and PTH low, n = 20. In group B, which could be anticipated as being at higher risk, we actually found the highest (p less than 0.05) bone Al content as compared to other groups, associated with a reduced bone formation rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630539 TI - Effect of body iron stores on serum aluminum level in hemodialysis patients. AB - To evaluate the influence of body iron stores on the serum aluminum (Al) level, we studied the correlation between iron status (the serum ferritin, serum iron and transferrin saturation) and serum Al levels in 68 severely anemic hemodialysis patients. Among them, 36 underwent the desferrioxamine (DFO) mobilization test. These 68 patients were divided into three groups according to their serum ferritin level. The basal Al level in the patient group was 41.4 +/- 37.4 micrograms/l (control, 4.1 +/- 2.4 micrograms/l). The serum Al level after DFO infusion of the patient group was 111.1 +/- 86.8 micrograms/l. A significantly higher basal Al and peak Al level after DFO infusion were found in group 1 patients (serum ferritin less than 300 micrograms/l) when compared to group 2 (serum ferritin 300-1,000 micrograms/l) and group 3 (serum ferritin greater than 1,000 micrograms/l) patients. A significant negative correlation between serum ferritin and basal serum Al (r = -0.544, p = 0.0001), as well as peak serum Al after DFO infusion (r = -0.556, p = 0.0001), was noted. Similarly, a negative relationship between serum Al (both basal and peak) and either serum iron or transferrin saturation was noted. However, there was no correlation between the serum Al level and the dosage of aluminum hydroxide. In conclusion, serum ferritin, serum iron and transferrin saturation were inversely correlated with serum Al in our hemodialysis patients. Iron deficiency may probably increase Al accumulation in these patients. PMID- 1630541 TI - Intraoperative versus routine hemodialysis in end-stage renal disease patients undergoing open-heart surgery. AB - Of 13 chronic hemodialysis end-stage renal disease (ESRD) patients undergoing open-heart surgery, 7 received intraoperative hemodialysis (IHD) during cardiopulmonary bypass and 6 received hemodialysis on a routine basis (RHD). Within the groups, IHD patients had significantly lower post-operative mean serum potassium and mean plasma creatinine concentrations compared to mean preoperative values. Postoperative mean BUN tended to decrease and mean serum bicarbonate concentration was unchanged as compared to mean preoperative values. In the RHD group, however, post-operative mean serum potassium concentration tended to increase, mean serum bicarbonate concentration significantly declined and mean BUN was unchanged as compared to mean preoperative values. An average of 2.1 +/- 0.5 liters of fluid was removed from the IHD patients during cardiopulmonary bypass. Post-operatively, 0 of 7 IHD patients versus 4 of 6 RHD patients required parenteral sodium bicarbonate therapy (chi 2, p less than 0.01). On average, RHD patients required hemodialysis 1 day after surgery, whereas IHD patients were hemodialyzed 2 days after surgery (p = 0.009). We conclude that IHD lessened postoperative hyperkalemia and metabolic acidosis and delayed postoperative hemodialysis by an additional day. IHD should be considered as an adjunct to RHD therapy in the management of ESRD patients undergoing open-heart surgery. PMID- 1630540 TI - Dialysis granulocytopenia is preceded by an increased surface expression of the adhesion-promoting glucoprotein Mac-1. AB - We studied the expression of Mac-1 on granulocytes (flow cytometry) from 9 patients (27 examinations) during hemodialysis with cuprophane membranes (CuM). Samples were drawn before dialysis and from the arterial and venous lines at 5, 15 and 180 min. Granulocytopenia was most pronounced after 15 min of treatment. Mac-1 expression on granulocytes increased during dialysis, and a pronounced enhancement occurred across the dialyzer. Mac-1 expression on granulocytes increased 116% across the dialyzer at 5 min, and the degree of Mac-1 mobilization at 5 min correlated with the degree of subsequent granulocytopenia at 15 min. In in vitro experiments, granulocytes from healthy blood donors were incubated with plasma drawn from the arterial and venous lines at 5 min. Plasma drawn from the venous line at 5 min had a greater ability to mobilize Mac-1 than plasma from the arterial line (p less than 0.002). This difference correlated with the degree of granulocytopenia at 15 min (r = 0.76, p = 0.01). Pieces of a washed CuM were incubated in normal human serum (NHS) preparations for different times. Inactivation of the alternative pathway of complement activation (NHS-50 degrees) did not alter the generation of Mac-1-mobilizating capacity compared to NHS. In contrast, inactivation of the classical pathway (NHS-EGTA) decreased the early but not the late generation of Mac-1-mobilizating capacity. Our results indicate that the early mobilization and not the absolute expression of Mac-1 correlates with granulocytopenia, and that sera in vitro attain Mac-1-mobilizating capacity more rapidly when the classical pathway of complement activation is intact. PMID- 1630542 TI - Urokinase concentration in the renal artery and vein. AB - To compare the fibrinolytic activity between the renal artery and vein and the systemic circulation, we measured tissue-type plasminogen activator (t-PA), urokinase and total fibrinolytic activity in the blood samples from both the left and right renal artery and vein and the anterior cubital vein of 7 kidney donors. Englobulin fibrinolytic activity was significantly higher in the renal vein [106.6 +/- 5.6 blood activator units (BAU)] than in the renal artery (90.6 +/- 4.1 BAU; p less than 0.001) and cubital vein (94.3 +/- 6.3 BAU, p less than 0.005), but there was no difference between renal artery and cubital vein. t-PA Ag was 2.9 +/- 1.1 ng/ml in the renal vein, 2.6 +/- 1.0 ng/ml in the renal artery and 2.6 +/- 1.1 ng/ml in the cubital vein. There was no difference between renal artery, renal vein and cubital vein. Urokinase was significantly higher in the renal vein (3.3 +/- 0.4 ng/ml) than in the renal artery (2.4 +/- 0.4 ng/ml; p less than 0.001) and cubital vein (2.6 +/- 0.4; p less than 0.005), but there was no difference between the renal artery and cubital vein. In all cases, there was no difference in the fibrin(ogen) degradation product concentration between the renal artery and vein and the cubital vein. These findings suggest that the kidney may be an essential organ for providing urokinase to the systemic circulation. PMID- 1630543 TI - Plasma 1,5-anhydroglucitol concentration in patients with end-stage renal disease with and without diabetes mellitus. AB - The plasma concentration of 1,5-anhydroglucitol, a new clinical marker of glycemic control in diabetic patients, was evaluated as a marker of glycemia in 83 diabetic and nondiabetic patients with end-stage renal disease. Plasma 1,5 anhydroglucitol concentration decreased and correlated inversely with blood glucose, hemoglobin A1c, or fructosamine in 48 diabetic patients with normal renal function. In 13 nondiabetic patients with end-stage renal disease not on dialysis, plasma 1,5-anhydroglucitol concentrations were lower than in 23 healthy subjects (6.22 +/- 2.10 vs. 24.20 +/- 7.50 micrograms/ml, respectively). The plasma concentration of 1,5-anhydroglucitol concentration in nondiabetic patients with end-stage renal disease was inversely correlated to the urinary N-acetyl beta-D-glucosaminidase activity (r = -0.634) but not to blood glucose, hemoglobin A1c, or fructosamine. Renal tubular damage may contribute to the low plasma concentration of 1,5-anhydroglucitol in this group. The plasma concentrations of this polyol decreased in both diabetic (4.63 +/- 1.08 micrograms/ml) and nondiabetic patients on hemodialysis (4.71 +/- 0.87 micrograms/ml). In these two groups, there was no correlation between plasma concentration of this polyol and blood glucose, hemoglobin A1c, or fructosamine. The plasma concentration of 1,5 anhydroglucitol decreased after a single hemodialysis session. The results showed that impaired renal function and removal of 1,5-anhydroglucitol by dialysis may contribute to its decreased concentration in patients with end-stage renal disease, but that glycemic control does not. Therefore, we should consider renal function when we use plasma 1,5-anhydroglucitol concentration as a marker of glycemic control in diabetic patients. PMID- 1630544 TI - Low doses of drugs able to alter intestinal mucosal permeability to food antigens (5-aminosalicylic acid and sodium cromoglycate) do not reduce proteinuria in patients with IgA nephropathy: a preliminary noncontrolled trial. AB - In an uncontrolled trial, patients with IgA nephropathy (IgAN) were treated with drugs that can alter the intestinal mucosal permeability to food antigens. These drugs are known to ameliorate urinary abnormalities and histological lesions of IgAN associated with ulcerative colitis or Crohn's disease [5-aminosalicylic acid (5-ASA)] or to prevent, in mice, the induction of IgAN-like disease by oral immunization [disodium cromoglycate (SCG)]. Nine patients [serum creatinine (s Cr) less than 2 mg/dl; 24-hour proteinuria higher than 1.5 g, but not nephrotic) were treated with 5-ASA (2.4 g/day for 6 months); 9 similar patients were treated with SCG (400 mg/day for 6 months); the follow-up extended to 6 months after stopping therapy. The 5-ASA group showed a slight but not significant decrease in s-Cr, 24-hour/proteinuria, IgA circulating immune complexes (IgA-CIC) and IgA rheumatoid factor (IgA-RF); serum beta 2-microglobulin and serum IgA were unchanged; 2 of 9 treated patients showed, after 6 months of therapy, a reduction in proteinuria of more than 50% that lasted for the subsequent 18 months. The SCG treated group showed a slight but not significant increase in 24-hour proteinuria and a significant decrease in serum IgA; unchanged were s-Cr, IgA-CIC, IgA-RF, serum beta 2-microglobulin; no patient treated with SCG showed a reduction in proteinuria of more than 50%. At the dosages and for the periods used, 5-ASA and SCG did not show a significant influence on clinical and laboratory parameters of disease in IgAN; other trials with increased dosages are warranted to definitely ascertain the possible therapeutic role of these drugs in IgAN. PMID- 1630545 TI - Two cases of persistent hypouricemia associated with diabetes mellitus. AB - Two patients with diabetes mellitus had persistent hypouricemia due to increased urate clearance; the degree of the apparent renal hypouricemia with uricosuria was quite mild. At the onset of diabetes, their serum urate levels were normal. Even after good diabetes control in both cases, hypouricemia continued. Based on the pharmacological evaluation in both patients, pyrazinamide administration could partially decrease urate clearance, however, suppression by pyrazinamide was less than in normal subjects, and probenecid increased urate clearance. These results suggest that the present cases had a renal abnormality affecting tubular presecretory reabsorption of urate, which might be due to diabetes mellitus. PMID- 1630546 TI - Detection of cellular proliferation during compensatory renal growth using flow cytometry. AB - Compensatory renal growth (CRG) consists of cellular enlargement and a small but consistent increase in DNA content. It has been assumed that the increase in total renal DNA content was due to new cell formation, however, the possibility of nuclear polyploidy remained an alternative explanation. To test the hypothesis whether cellular hyperplasia is the cause of the increase in DNA content during compensatory growth after renal deprivation, we performed cell cycle analysis using flow cytometry. Following unilateral nephrectomy, the amount of cortical cells in the S phase increased by 12% at 10 h while the number of cells in the G2M phase increased by 7% at 120 h. Medullary cells entering the S phase increased by 26% at 24 h and those in G2M increased by 12% at 168 h. DNA synthesis and replication occurs during CRG following unilateral nephrectomy as evidenced by an increase in cells entering both the S and G2M phases of the cell cycle. The increase in DNA content during CRG is a result of cellular proliferation and not polyploidy. PMID- 1630547 TI - Effect of ciclosporin on cardiac output and regional blood flow in rats: ciclosporin-induced nephropathy and its prevention with calcium channel blocker. AB - The effect of ciclosporin (CS) on cardiac output (CO) and regional blood flow was studied using the microsphere method in heminephrectomized rats with and without renal arterial clamping prior to the administration of CS. The effect of a calcium (Ca) channel blocker, verapamil, was also examined on CS-induced nephropathy. CS at a dose of 40 mg/kg per day was given orally using a gastric tube for 7 days. Verapamil was given in the drinking water for 7 days. Significant increases in blood urea nitrogen (BUN) and serum creatinine (sCr) with a significant decrease in renal inulin clearance (CIn) were noted after 7 days of CS administration in both intact and ischemic-kidney groups, indicating the development of CS-induced nephropathy. The ischemic-kidney group showed a significantly severe nephropathy as compared with the intact-kidney group. As for change in CO and regional blood flow, CS caused a significant decrease in CO, renal blood flow (RBF) and brain blood flow, while hepatic arterial blood flow and muscular blood flow significantly increased. The renal outer cortical blood flow decreased markedly while the inner cortical blood flow remained unchanged. Although verapamil slightly but significantly decreased mean arterial blood pressure in CS-treated rats, CO and its distribution did not change. BUN and sCr were not significantly ameliorated in the intact-kidney group. However, in the ischemic-kidney group, verapamil caused a significant improvement in RBF, ameliorating CS-induced elevation of BUN and sCr, and a decrease in CIn.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630548 TI - Phlebotomy for erythropoietin-induced malignant hypertension. AB - Four patients on regular dialysis treatment whose blood pressure was well controlled, developed malignant hypertension while receiving maintenance recombinant human erythropoietin (r-Hu-EPO). None of these patients had a haematocrit greater than 35% at any stage, and clinically, none had any evidence of fluid overload. Initially, they were all managed by stopping r-Hu-EPO and intensification of antihypertensive therapy. However, none of the patients responded, and venesection of 500 ml of blood was performed in each case with swift and sustained response. PMID- 1630549 TI - Hypertension in unilateral atrophic kidney secondary to ureteropelvic junction obstruction. AB - A patient with atrophic unilateral hydronephrosis due to ureteropelvic junction obstruction associated with hypertension was successfully treated by nephrectomy. Preoperatively, plasma renin activity was elevated in both the peripheral vein and affected renal vein. Renin concentration in the resected kidney was high, and immunohistochemical localization of renin was observed along the afferent arterioles of the juxtaglomerular apparatus and in arterioles at some distance from the glomeruli. PMID- 1630551 TI - Helicobacter pylori infection in dialyzed patients: bismuth therapy and pharmacokinetics. PMID- 1630550 TI - Idiopathic hypercalciuria causing osteoporosis and hypocalcemia. AB - Idiopathic hypercalciuria, though a common cause of nephrolithiasis, has not been recognized to cause hypocalcemia and severe bone disease. We describe an adolescent with idiopathic hypercalciuria who presented initially with severe hypocalcemia and osteoporosis and this was later complicated by recurrent renal calculi formation after calcium and vitamin D supplement. After treatment with thiazide, hypercalciuria was controlled and serum biochemistry normalized. While idiopathic renal hypercalciuria may cause a negative calcium balance in adults, a variant of this syndrome with severe renal calcium leak occurring in a growing subject could lead to severe hypocalcemia and osteoporosis. PMID- 1630552 TI - Red cell lipid peroxidation and antioxidant system in chronic renal failure patients treated with recombinant human erythropoietin. PMID- 1630553 TI - Massive hemorrhagic necrosis of small intestine due to mesenteric vein thrombosis: an unusual complication of nephrotic syndrome. PMID- 1630554 TI - Vinorelbine therapy in a hemodialyzed patient. PMID- 1630555 TI - Renal cell carcinoma of the native kidney in a female renal allograft patient without acquired cystic kidney disease. PMID- 1630556 TI - Is transfusion the only risk factor for HCV infection among hemodialyzed patients? PMID- 1630557 TI - Anomalous neutrophil inositol triphosphate production in idiopathic calcium oxalate nephrolithiasis. PMID- 1630558 TI - Hydrocarbons and renal failure: primary damage in glomerulonephritis is tubular, not glomerular. PMID- 1630559 TI - Enalapril-associated anemia in a patient with IgA nephropathy and hypertension. PMID- 1630560 TI - Infected graft fistula following dental surgery. PMID- 1630561 TI - Torulopsis glabrata peritonitis in a chronic hemodialyzed patient. PMID- 1630562 TI - Spontaneous resolution of hydrothorax in continuous ambulatory peritoneal dialysis. PMID- 1630563 TI - [Plastic surgery for facial nerve paralysis]. PMID- 1630564 TI - [Unbranched-site aneurysm of intracranial internal carotid artery]. AB - Most intracranial saccular aneurysms arise from the angle between a parent vessel and an arterial branch. Saccular aneurysms without relation to any arterial branch are rare. During the last 24 years, 210 patients with intracranial internal carotid artery (ICA) aneurysms were directly operated on at our institution. We found eight saccular aneurysms arising from intracranial ICA without relation to any arterial branch. So we call them unbranched-site aneurysms of intracranial ICA, and describe their unique characteristics. Of the eight cases with unbranched-site aneurysm of intracranial ICA, three were men and five were women. The age ranged from 31 to 61 years with an average age of 48. Seven cases suffered a subarachnoid hemorrhage due to ruptured unbranched-site aneurysm, and the other case had been admitted to our department because of accompanying ruptured left internal carotid-posterior communicating aneurysm. All cases of unbranched-site aneurysm presented intraoperative and/or angiographic findings of arteriosclerosis, and five of the patients had a past history of hypertension. Of the four unbranched-site aneurysms at the C2 portion of ICA, two arose from the lateral wall, one arose from the superior wall and the other arose from the infero-lateral wall of ICA. Of the four unbranched-site aneurysms at the C1 portion of ICA, three arose from the superior wall and the other arose from the supero-medial wall of ICA. Radical operation was performed in all cases and intraoperative rupture occurred in two cases. It was suggested that arteriosclerotic change in the arterial wall, and local hemodynamic stress played important roles in the development of unbranched-site aneurysms of intracranial ICA. PMID- 1630565 TI - [Diagnosis and treatment of disseminated intravascular coagulation associated with neurosurgical diseases; a proposal of a new scoring system for DIC]. AB - The occurrence of disseminated intravascular coagulation (DIC) is not rare in neurosurgical patients. We investigated the therapeutic effects of gabexate mesilate (FOY) for DIC or DIC preparatory state in 70 cases. Underlying diseases were head injuries in 31 cases, intracranial hemorrhages in 19, subarachnoid hemorrhages in 10, cerebral infarctions or embolisms in 5, brain tumors in 3 and other diseases in 2. DIC or DIC preparatory states were induced by severe brain damage (26 cases), infection (26 cases), failure of other organs (6 cases), shock (5 cases), and others. On the basis of the clinical coagulation studies of these patients, we retrospectively established a new scoring system for DIC (neurosurgical DIC score) associated with neurosurgical diseases and evaluated whether it was useful. Because the original DIC score proposed by the Research Committee on Blood Coagulation Disorders supported by the Japanese Ministry of Health and Welfare was not correlated with the level of consciousness representing the primary brain damage, it was likely to be underestimated in neurosurgical patients. Therefore, we included the level of consciousness with a new DIC scoring system. The neurosurgical DIC score was calculated from platelet count (score 0-3), FDP (score 0-3) and the level of consciousness (score 0-2), and was diagnosed as DIC preparatory state if it was 3, calculated from 2 of the 3 parameters, and as DIC if it was over 4. The score should be checked twice if it was 3, especially after operation. The neurosurgical DIC score was significantly correlated with the original DIC score.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630566 TI - [Intraoperative monitoring of facial electromyographic responses during neurovascular decompressive surgery for hemifacial spasm]. AB - In this paper, we reported our experience of intraoperative facial electromyographic recordings obtained during microvascular decompression for hemifacial spasm. MATERIALS AND METHODS: Intraoperative electromyographic recordings from the mentalis muscle during stimulation of the temporal branch of the facial nerve has been attempted in 31 patients. No muscle relaxants were used except for those before intubation. Of 31 patients, 22 were female and 9 were male. The age on admission ranged from 31 to 60 years with a mean of 54 years. RESULTS: 1. Abnormal response appeared with a latency of about 10 msec after stimulation. This response disappeared in 30 out of 31 patients at the end of operation. In 4 patients, the abnormal response disappeared prior to decompression of the nerve. 2. 30 patients in whom the abnormal response disappeared were free of spasm immediately after surgery. Hemifacial spasm has been relieved in 28 patients with a follow up period of 6 months to 2 years and 7 months. The remaining two patients had mild spasm. The one patient in whom the abnormal response did not disappear had persistent hemifacial spasm. CONCLUSION: The authors think that intraoperative facial electromyographic recording is useful to identify the blood vessel that is causing the spasm and to ensure that decompression of the nerve has been accomplished. PMID- 1630567 TI - [An analysis of lymphokine gene expression within astrocytoma]. AB - Expression of the lymphokine genes in human astroglial cell lineage was studied. Primers for 9 different human lymphokines, from IL-1 alpha to IL-8, were used to analyze RNA transcripts in 5 cultured human astrocytoma, one neuroblastoma cell line and 4 fresh brain specimens by polymerase chain reaction (PCR). mRNA transcripts of neither IL-1 nor IL-3, the biological activities of which were observed in rat primary cultured astrocytes, could be detected within these cell lines. Two out of 5 unstimulated astrocytomas, U138 and U373, expressed IL-6 genes. IL-8 gene was detected within U87, U138, U251, U373 glioma cells. After stimulation with IL-1 beta, all astrocytoma and one neuroblastoma cell line expressed IL-6 and IL-8 genes. In addition to the cultured cells, we examined IL 6 and IL-8 gene expression within human malignant astrocytoma specimens. The result shows that three out of four glioma specimens expressed IL-6 and IL-8 genes. From these results, it is suspected that astroglial cell-derived IL-6 or IL-8 may participate in local immune reactions accompanying infection, degeneration and malignancies in the central nervous system. PMID- 1630568 TI - [Linac based radiosurgery; a technical report]. AB - A method for highly dose-localized irradiation using a linear accelerator (linac) for a brain tumor has been developed. The method requires a linac, a computed tomography (CT) system, a CT simulator, and a treatment planning system for radiotherapy, with which most major radiotherapy centers are equipped. To immobilize a patient during irradiation, a custom-made device made of synthetic material which became flexible with heating was used. With the CT system and the CT simulator the target was identified and geometrical data for positioning the tumor at a point to which x-ray beams were directed (an isocenter of the linac) were obtained. By rotating a treatment couch it was made possible for the x-ray source to rotate around the isocenter on multiple planes. Dose distribution obtained with this method was compared to that of the gamma unit and found comparable. Since the method requires no invasive procedure, it appears suitable for treatment, with fractionated irradiation, of malignant tumors. PMID- 1630569 TI - [Germinoma with granulomatous reaction arising from the corona radiata; case report and review of articles]. AB - We report a rare case of germinoma with granulomatous reaction arising from the corona radiata. This 20-year-old man was admitted to our hospital complaining of progressive motor weakness on the right side. CT demonstrated a poorly demarcated high density area in the left corona radiata, which was heterogeneously enhanced after administration of contrast medium. Moreover, the continuity of the mass to the ventricular wall was confirmed on MRI. At the first operation, subtotal removal of the tumor was performed through a fronto-parietal craniotomy. The diagnosis for the specific neoplasm was not established histologically, but granuloma caused by fungal infection was the most likely cause of the lesion. We tried amphotericin B (AmB), and remission of the tumor was obtained. However, during the following 3 months, the size of the tumor gradually enlarged again. AmB was repeatedly administered, but this time the treatment was ineffective. Six months later, on May 21, 1990, the second operation was performed and histological examination revealed typical germinoma consisting of two-cell pattern. Subsequently, the patient underwent focal irradiation of 33 Gy to the tumor site, and the tumor completely disappeared. As intracranial germinomas are observed to be successfully cured by radiotherapy and/or chemotherapy, choice of the therapeutic management must be carefully determined according to the histological diagnosis, especially in young people. A variety of locations of germinomas and the accompanying granulomatous reactions could create some diagnostic confusion, so great care must be taken in the treatment of much intracranial germinomas. PMID- 1630570 TI - [Subclavian artery to internal carotid artery bypass with saphenous vein graft in the treatment of bilateral common carotid artery occlusion; a case report]. AB - A case of left common carotid artery occlusion, which was treated by a saphenous vein graft, is reported. A 49-year-old right handed male was admitted to the hospital because of right hemiparesis and aphasia. These symptoms disappeared spontaneously two weeks after admission. However, visual acuity remained impaired on the left side due to occlusion of the central retinal artery. Angiography revealed complete occlusion of the common carotid arteries as well as patency of the internal carotid arteries on both sides. PET and 123I-IMP-SPECT studies showed hypoperfusion in the left cerebral hemisphere. To restore the blood flow as well as to remove the source of the emboli, endarterectomy was performed on the left internal carotid artery. This was followed by a saphenous vein graft between the left subclavian and the internal carotid artery. Postoperative angiography revealed patency of the bypass, and a SPECT study revealed increased blood flow in the left cerebral hemisphere. The patient has remained in stable condition during the following 30 months with no neurological problems. We conclude that in the treatment of complete occlusion of the common carotid artery and subsequent cerebral hypoperfusion, a bypass graft between the internal carotid and the subclavian artery is quite effective, and that the site of the bypass graft should carefully be sought for by using preoperative angiographic studies. PMID- 1630571 TI - [A case of giant aneurysm of the posterior cerebral artery, treated with a detachable balloon]. AB - We report a case with a giant PCA aneurysm successfully treated using the detachable balloon technique. The case was a 52 year-old man with episodes of minor stroke probably due to the giant aneurysm. The aneurysm was located in the P2 segment of the right PCA and was broad-based. Clipping of the neck was considered to be impossible and proximal clipping was the alternative treatment. Instead of surgery, proximal occlusion of the PCA was performed with the use of a detachable balloon. PMID- 1630572 TI - [A septated syringomyelia with a dramatic clinical course in a young patient with MELAS; a case report]. AB - This is a report of a young girl who showed a recurrence of acute worsening and remission of neurological manifestations, with consistent MRI demonstration of transaxial septated syrinxes in the cervical and the lumbar spinal cord in addition to a tight filum terminale. This 8 year-old girl had developed normally since her birth until August 1989 when she developed a gait disturbance. This worsened acutely on January 1, 1990, with the additional manifestation of a urinary bladder disturbance. General examination failed to show any abnormality or scoliosis. Neurologic examination revealed a monoparesis of the right lower extremity with muscle atrophy and pyramidal tract sign. Fecal constipation and urinary retention were noted. The MRI T1 weighted sagittal image demonstrated an incontinuous low intensity signal in the C1-C7 as well as in the T12-L2 without swelling of the cord. The axial image clearly demonstrated the septations in the syrinx which looked like eye glasses. No definite Gd enhancement was demonstrated. Chiari malformation was not associated, but the tethered cord was well identified. With the administration of steroid, she showed a marked improvement of neurological manifestations. She was able to urinate without difficulty and also walk by herself. For one month thereafter she remained well with minor neurological deficits until she developed a worsening of the gait disturbance with a newly manifested weakness of the left upper extremity. Sensory impairment was also demonstrated below L3. In contrast to the worsening of the clinical symptoms, no definite change in the abnormalities found by MRI was noted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630573 TI - [Intrathecal dissemination of meningiomas; a case report]. AB - A case of the cytologically verified intrathecal dissemination of benign meningiomas was reported. A 36-year-old man was admitted to our hospital because trans-sphenoidal surgery was planned for the repair of CSF rhinorrhea caused by a recurrent pituitary adenoma. The CT scan demonstrated incidental multiple tumors spread throughout in the pontomedullary and ambient cisterns. The head and spinal MRI showed more than fifteen small tumors in the posterior fossa and the thoracic spinal canal. CSF cytology revealed benign fibroblastic or meningotheliomatous meningioma with whorl formation and psammoma body. Several comments were made on the mechanism of the intrathecal dissemination of the meningiomas. PMID- 1630574 TI - [Clival chordoma in an infant; case report and review of the literature]. AB - Skull base chordoma in infants is a very rare entity in spite of its congenital origin; only 11 clinical cases can be found in the literature so far. Here we report such a case and review the literature. The case is that of a 3.5-year old boy suffering from left abducent nerve palsy for 5 months. CT scan revealed an isodense mass lesion with bone destruction involving the clivus and left petrous apex, and was homogeneously enhanced on post-contrast study. MRI disclosed the clival tumor as a long T1 and long T2 mass. Angiogram showed no tumor stain. The tumor was preoperatively diagnosed as clival chordoma, and was partially removed via left transpetrosal-transtentorial approach. The tumor was found to extend into the subdural space through Dorrello's canal and compress the abducent nerve. Histological examination with H & E, PAS, mucicarmine, and reticulin stainings led us to a diagnosis of "typical chordoma". Electron microscopy demonstrated the mitochondria-endoplasmic reticulum complexes (MERC), glycogen granules, and vacuoles in the tumor cells. Postoperative irradiation (total dose 55 Gy) was performed. At present, 30 months after the operation, no evidence of tumor regrowth nor hypothalamus-pituitary deficiency is recognizable and the patient is free from left abducent nerve palsy. It is concluded that skull base chordoma in infants should be postoperatively irradiated in an appropriate manner. PMID- 1630575 TI - [A case of unilateral atypical moyamoya disease of adult onset with stenosis of the basilar artery]. AB - A 29-year-old, 39-week-pregnant female who had headache and nausea was admitted to our hospital. She bore a baby son by natural delivery after several hours. After labor, her headache was continuous. Brain CT scan demonstrated intracerebral and intraventricular hemorrhage. After conservative treatment for two weeks, her only neurological deficiency was visual field defect. Angiography demonstrated that her left internal carotid artery had partial stenosis at the C2 portion. Her right internal carotid artery had stenosis at the C2 portion. Her right middle cerebral artery was occluded at the M1 portion, and abnormal vascular networks had developed in the ganglionic region. Stenosis was also found in the basilar artery. We diagnosed her as being a case of adult-onset, unilateral, atypical Moyamoya disease with basilar artery stenosis. As our case was of adult-onset, and as she showed no ischemic signs, we did not think that reconstructive surgery was indicated. About the posterior circulation of Moyamoya or atypical Moyamoya disease, it was reported that in cases of juvenile onset the vertebral, basilar or posterior cerebral artery was sometimes stenosed or occluded, but, in adult-onset cases, stenosis or occlusion of the posterior cerebral artery would be an abnormality. Our case is a very rare example of unilateral atypical Moyamoya disease of adult onset with basilar artery stenosis. PMID- 1630576 TI - Ultrastructure of pre-synaptic input to motor neurons in Onuf's nucleus: controls and motor neuron disease. AB - Ultrastructural analyses of sphincteric motoneurons in Onuf's nucleus at S2 were undertaken in human spinal cord obtained 3-6 h post-mortem from three subjects with no neurological disease ('controls') and five in which death was due to motor neuron disease (MND). Neurons in specified locations within Onuf's nucleus of control subjects ranged between 17.8 and 71.7 microns diameter (mean 38.6 microns). Analyses of synaptology revealed five ultrastructural classes of presynaptic terminal synapsing with the neuronal surface membrane. When classified by size, vesicle morphology, and synaptic site structure these conformed to the S, F, T, M and C-terminals defining somatic motoneurons. No terminals characteristic of autonomic motoneurons were found. In MND subjects, neurons in Onuf's nucleus at S2 were preserved despite a paucity of neurons in medial and lateral motor nuclei and were of similar size range to those in control subjects. The morphological classes of pre-synaptic terminal found in controls, also characterized sphincteric motoneurons in MND subjects, including the C-type terminal. The presence of C-terminals indicates (i) that sphincteric motoneurons are somatic alpha-motoneurons, and (ii) that hypotheses explaining the survival of sphincteric motoneurons in MND on the basis of Onuf's nucleus being an extension of the pre-ganglionic parasympathetic nucleus, or having intrinsic autonomic properties are incorrect. PMID- 1630577 TI - Cytoskeletal protein abnormalities in patients with olivopontocerebellar atrophy- an immunocytochemical and Gallyas silver impregnation study. AB - A highly sensitive silver technique for glial cytoplasmic inclusions (GCI) in olivopontocerebellar atrophy (OPCA) was applied to tissues from 15 patients with neurodegenerative disorders including OPCA, Joseph disease, Alzheimer's disease (AD), Huntington's chorea, Pick disease and three control non-neurological subjects. Brain tissue from both OPCA and AD impregnated positively. Neurons, astroglia and oligodendroglia in the putamen, pontine nucleus and inferior olivary nucleus all impregnated in addition to white matter oligodendroglia. Neuronal inclusions in the pontine nucleus appeared as compact or fibrillary masses, and GCI-bearing oligodendroglia and astrocytes showed homogeneously impregnated somata. The myelinated pontocerebellar tract and the white matter surrounding the inferior olivary nucleus contained a small number of impregnated nerve fibres with a hollow structure, which resembled the myelin sheath. Immunocytochemical studies to clarify these argyrophilic structures in the OPCA subjects employed paired helical filament (PHF), microtubule associated proteins (MAPs), MAP1, MAP2, MAP5, tau, ubiquitin, neurofilament (200 or 70 kilodaltons) and myelin basic protein (MBP) antisera. GCI-bearing white matter oligodendroglia expressed PHF, tau, MAP5 and ubiquitin immunoreactives and non-argyrophilic astroglia were positive for MAP5 antiserum alone. In the putamen, pontine nuclei and inferior olivary nuclei, impregnated neurons as well as the GCI-bearing oligodendroglia immunostained with PHF, tau, MAP5 and ubiquitin antisera and impregnated astroglia were also immunoreactive to these antisera except for being tau negative in the putamen. Silver impregnated nerve fibres showed only MBP immunoreactivity. These findings indicate that the argyrophilia in the OPCA subjects closely correlates with PHF and tau immunoreactivities. PMID- 1630578 TI - The number and mean volume of neurons in the cerebral cortex of rats intoxicated with acrylamide. AB - Acrylamide was given in an accumulated dose of 500 mg/kg to rats by intraperitoneal injection in two different dosing schedules: 50 mg/kg twice a week for 5 weeks and 33.3 mg/kg twice a week for 7.5 weeks. The effect of acrylamide intoxication on the neurons in the cerebral cortex of the rat was studied using unbiased stereological methods. A reduction of brain weight of 8% was seen in both the intoxicated groups. The volume of neocortex was significantly decreased in the experimental groups, but the density of neurons was increased resulting in an unchanged total number of neurons. The mean volume of neurons in neocortex was significantly decreased in both acrylamide intoxicated groups. There was no difference between the two different intoxication schedules. The possibility that acrylamide causes neuronal death and the effect of eventual differential cellular sensitivity is discussed. PMID- 1630579 TI - A preliminary investigation of promotion of brain tumours by hexachlorophane in Sprague-Dawley rats transplacentally exposed to N-ethylnitrosourea. AB - Two-stage carcinogenesis (initiation and promotion) has been demonstrated in various mammalian tissues, but there is no conclusive evidence that it occurs in the nervous system. The present work has investigated the possibility that it might occur in the brain of the rat. Pregnant Sprague-Dawley rats were given an initiating dose (10 mg/kg intravenously (i.v.)) of N-ethylnitrosourea (ENU), which resulted in a low but consistent yield of brain tumours in the offspring. The dose was determined in a prior dose-response investigation. The 'initiated' offspring were treated postnatally with the putative promoter, hexachlorophane, and its ability to increase tumour incidence was examined by standardized step sectioning of the brain from rats killed at 6 months. There was no evidence of promotion of ENU-induced brain neoplasms by hexachlorophane in the rat. The experimental procedure led to a reproducible incidence of glial tumours in the pups. PMID- 1630580 TI - Dying back type axonal degeneration of sensory nerve terminals in muscle spindles of the gracile axonal dystrophy (GAD) mutant mouse. AB - A disorder of the gracile axonal dystrophy (GAD) mutant mouse is characterized by a neuromuscular disease with sensory ataxia (detectable 30 days after birth) and paresis of the hindlimbs (detectable at 80 days). In the sensory ataxia stage, histological study of the primary sensory system shows that, in addition to the lesions in the central nervous system, peripherally projecting axons have also started to degenerate at their distal ends in muscle spindles. Although the structure of Ia fibre endings appear normal until 15 days after birth, initial changes in the annulo-spiral structure are detected around the 20th day by a degeneration of the terminal axons. Degeneration then progressed proximally and the secondary endings also start to degenerate. Neuron cell bodies located in the dorsal root ganglia are morphologically intact until the later stages. Chronological studies indicate that, although axonal degeneration progresses throughout life, it is accentuated during the rapid somatic growth period. Around 50 days of age, transient regeneration takes place at axonal endings when somatic growth has attained a plateau. Such primary sensory endings tend to be restored by fine, multiple axons which gain access to the intrafusal fibres through the original endoneurial tubes. Ultrastructural observations at the fully affected stage show intrafusal muscle fibres lying scattered within spindles due to loss of the fine network of inner capsule layers and an almost complete loss of sensory endings from the surface of intrafusal muscle fibres. These results indicate that this mutant mouse is a useful model for naturally occurring 'dying back' type axonal degeneration or 'central and peripheral distal axonopathies', and would provide significant information about the complete evolution of the pathological processes involved. PMID- 1630581 TI - The binding of basic fibroblast growth factor to ischaemic neurons in the rat. AB - Transient occlusion of the right middle cerebral artery for 15 min produced a small ischaemic lesion in the dorsal portion of the right striatum in rats as seen on days 3, 7 and 14 post-operatively. The lesions consisted mainly of reactive astrocytes and 'ischaemic neuron's with chromatin-condensed (pyknotic) nuclei and homogenously eosinophilic cytoplasm. The incubation of tissue sections with basic fibroblast growth factor (bFGF) followed by anti-bFGF, or with biotinylated bFGF without anti-bFGF, labelled virtually all ischaemic neurons, indicating that bFGF had bound to the latter. The pretreatment of sections with heparitinase prevented the binding of bFGF to these cells, suggesting that the chemical substrate for the bFGF binding was heparan sulphate. In light of the findings that many normal-looking neurons were observed in the corresponding portion of the right striatum in most rats on post-operative days 28 and 90, the appearance of bFGF-binding sites in ischaemic neurons may contribute to the repair process of injured neurons. PMID- 1630582 TI - Development and control of the opioid inhibition of gonadotropin secretion during the sexual maturation of the male rat. AB - The endogenous opioid system tonically inhibits the LH-releasing apparatus in adult male rats but not in immature animals. To determine the relationship between the onset of this effect and the peripubertal testosterone rise, male rats were examined at 5-day intervals from day 25 through day 65. They were injected subcutaneously with saline, 0.25 or 1.0 mg/kg body weight naloxone and sacrificed 20 min later. Another group of immature males was castrated, implanted with testosterone-filled capsules and tested with naloxone 4 days later. The peripubertal increase in testosterone and the ability of naloxone to increase serum LH concentrations were both first statistically significant on day 45. Testosterone treatment of immature rats did not induce a naloxone effect. The ability of hypothalamic fragments to release LHRH in vitro in response to naloxone also appeared to occur at the same time as the peripubertal testosterone rise. Hypothalamic fragments obtained from immature male rats treated in vivo with testosterone were capable of responding to naloxone with LHRH release in vitro. These data suggest that in the rat the maturation of the endogenous opioid system is a component of male puberty that is induced by the peripubertal testosterone rise. PMID- 1630583 TI - Effect of retinoic acid deficiency on in vivo and in vitro GH responses to GHRH in male rats. AB - Retinoic acid has recently been shown to increase growth hormone (GH)-gene transcription rate and GH synthesis in vitro. To investigate the role retinoic acid plays in the neuroregulation of GH secretion we have studied GH responses to growth hormone-releasing hormone (GHRH) in retinoic acid-deficient rats. Compared to normally fed male rats, retinoic acid-deficient rats showed a marked impairment in body weight, which was statistically significant after 3 weeks and maximal after 5-6 weeks (p less than 0.001). Yet, in vivo GH responses to different doses of GHRH (1, 5 and 25 micrograms/kg) in pentobarbital-anesthesized rats were similar in both groups. Also, in vitro GH responses to GHRH, forskolin, and KCl were similar in perfused pituitary cells taken from control and retinoic acid-deficient rats. However, further studies carried out in freely-moving rats showed the typical GH secretory pattern usually found in male rats of the control group, while retinoic acid-deficient rats displayed a highly variable GH secretory pattern with GH peaks of much lower amplitude. Finally, after gel electrophoresis of in vitro 35S-labelled proteins, no differences were observed in the molecular forms of GH. Considering these findings on normal pituitary responsiveness and alterations in GH pulsatility, our data suggest that retinoic acid deficiency leads to an alteration in the neuroregulation of GH secretion at the central level. PMID- 1630584 TI - Type II corticosteroid receptor-like immunoreactivity in the rat cerebellar cortex: differential regulation by corticosterone. AB - Type II corticosteroid receptor-like immunoreactivity (type II-ir) was localized at the light- and electron-microscopic levels in the rat cerebellar cortex using BUGR2 monoclonal antibody. In intact rats, type II-ir was observed in the nuclei of basket, stellate, Golgi and Purkinje cells. After 1 week of adrenalectomy, type II-ir was barely resolvable in basket, stellate, Golgi and most Purkinje cells. Vermal Purkinje cells showed intense nuclear and cytoplasmic type II-ir. After 4 weeks of adrenalectomy, type II-ir was markedly reduced in most vermal Purkinje cells, however a few in lobules 1-3 and 9 and 10 retained diffuse immunoreactivity. Acute treatment with corticosterone restored nuclear type II-ir to basket, stellate, Golgi and Purkinje cells in the cerebellar hemispheres, flocculi and paraflocculi. In the vermis most Purkinje cells showed nuclear type II-ir following corticosterone treatment. Diffuse type II-ir was, however, retained in a few Purkinje cells in vermal lobules 1-3, 9 and 10. The distribution of GABA-like immunoreactivity (GABA-ir) in the cerebellar cortex was not altered by adrenalectomy or acute corticosterone treatment. 30-60% of type II ir Purkinje cells in intact rats were GABA-ir. In adrenalectomized and corticosterone-treated rats, a similar proportion of type II-ir Purkinje cells were GABA-ir. The differential regulation of neuronal type II-ir in the cerebellum by corticosterone may account for some of the known effects of glucocorticoids on motor coordination. PMID- 1630585 TI - Postnatal development of corticosteroid receptor immunoreactivity in the rat cerebellum and brain stem. AB - The postnatal development of corticosteroid receptor immunoreactivity in the rat cerebellum and related brainstem nuclei was studied using a type I receptor antiserum, MINREC4, and a type II receptor monoclonal antibody, BUGR2. Type I receptor immunoreactive (ir) Purkinje cells were first observed at postnatal day 5 (P5), and increased to adult levels by P20. Type I-ir cells, presumably migrating granule cells, were observed in the developing molecular layer of the cerebellum at P5. By P30, the density of type I-ir cells in the definitive molecular and granular layers was still less than adult levels. In contrast, type II-ir Purkinje cells were first observed at P15 and increased to adult levels by P20. No type II-ir cells were observed in the proliferative and migratory zones of the molecular layer. By P30, the density of type II-ir cells in the molecular and granular layers was far less than adult levels. In the deep cerebellar nuclei and most brain stem nuclei type I-ir was observed at P5 and developed to adult levels by P30. Type II-ir was observed in the deep cerebellar nuclei, red and medial vestibular nuclei by P15. The pontine and inferior olivary nuclei showed type II-ir cells by P10. Type II-ir in these regions developed to adult levels by P30. The earlier development of type I-ir suggests that the type I receptor may mediate the actions of corticosteroids in the cerebellum and related brain stem nuclei during early postnatal life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630586 TI - Involvement of arachidonic acid cascade pathways in interleukin-6-stimulated corticotropin-releasing factor release in vitro. AB - We have demonstrated that centrally administered interleukin-6 (IL-6) stimulates adrenocorticotropin (ACTH) secretion by a direct effect on corticotropin releasing factor (CRF) release from the hypothalamus. Since metabolites of the arachidonic acid cascade (AAC) have been implicated in mediating actions of cytokines in different tissues and some AAC inhibitors were able to block pyrogenic effects of cytokines and suppress IL-1-induced ACTH secretion, we decided to examine the mechanism of IL-6 action on CRF release in vitro. After a 60-min preincubation in Krebs-Ringer bicarbonate buffer, medial basal hypothalami (MBH) were preincubated for 30 min with dexamethasone (DEX), a phospholipase A2 (PLA2) inhibitor, to block arachidonic acid (AA) formation, or with inhibitors of AA metabolism: a cyclooxygenase inhibitor--indomethacin (IND); a lipoxygenase inhibitor--5,8,11-eicosatriynoic acid (ETI), and an epoxygenase inhibitor- clotrimazole (CLO). Then, the medium was discarded and MBH were incubated with medium or the above compounds and/or IL-6 for 30 min, and CRF release into the incubation medium was measured by radioimmunoassay. As reported previously, 10( 13) M IL-6 increased CRF release, which was significantly suppressed by DEX in a dose-dependent manner. The suppression was already highly significant at a concentration of 10(-11) M DEX and became maximal at 10(-7) M, at which concentration CRF release was no longer stimulated by IL-6. The response to IL-6 was completely blocked at the highest DEX concentration evaluated (10(-5) M). CLO also suppressed IL-6-induced CRF release with a minimal effective dose of 10(-9) M. Suppression was complete at 10(-7) and 10(-5) M.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630587 TI - Identification of neurotensin-immunoreactive cells in the anterior pituitary of normal and castrated rats. A double immunocytochemical investigation at the light and electron-microscopic levels. AB - The localization of neurotensin (NT) has been studied in the rat pituitary by means of immunocytochemistry at the light- and electron-microscopic levels. Cells immunoreactive for NT (NT-IR) were observed in the anterior lobe of rats of both sexes. Following an elution-restaining procedure, it was found that most of these NT-IR cells correspond to cells also reacting to beta-LH or FSH antisera. However, a few NT-IR cells did not stain for beta-LH nor FSH, but for TSH. The subcellular localization of NT was studied at the electron-microscopic level by means of the immunogold procedure. The immunoreactivity was always localized over the secretory granules. By using two sizes of gold particles, it was shown that NT- and beta-LH-IR were colocalized in part of the cell granules. Castration caused a progressive decrease of the NT-IR in the beta-LH- or FSH-positive cells, while the number of NR-IR, TSH-IR cells increased. After 2 weeks, NT-IR was mainly observed in this latter cell type. The present work demonstrates that NT IR is localized within the secretory granules of the gonadotrophs and a few thyrotrophs, indicating that NT could be released together with gonadotrophins and TSH. Moreover, since gonadectomy results in typical qualitative and quantitative changes of NT-IR gonadotrophs, the intervention of the pituitary NT in the regulation of the hypophysogonadal axis is strongly suggested. PMID- 1630588 TI - Endothelin-induced biphasic response of lactotrophs cultured under different conditions. AB - Endothelin (ET), a recently discovered vasoconstrictor peptide, is widely distributed in different tissues including brain and pituitary. Although evidence regarding the role of ET in neuroendocrine processes is still fragmentary, it appears that the release of several anterior pituitary (AP) hormones can be modulated by peptides of the ET family. In the present study, we compared the effects of ET-1 and ET-3 on the release of PRL from AP cells cultured in serum free (SFM) or serum-containing (SCM) medium. AP obtained from adult male rats were enzymatically dispersed, and the cells were plated in either SFM or SCM. After 4 days, cells were incubated with ET-1 or ET-3 for designated periods of time, and PRL levels in the incubation media were measured by RIA. When AP cells maintained in SCM were exposed to ET for 20 min, both peptides inhibited PRL release, with ET-1 being a more potent inhibitor than ET-3. In contrast, a biphasic response was observed in cultures grown in SFM: low concentrations of ET peptides inhibited the secretion of PRL, while high concentrations caused a significant stimulation. Further characterization of the effects of ET-1 revealed that the stimulatory phase was relatively short (15-30 min) and was followed by inhibition of PRL release. The addition of either horse serum or fetal bovine serum to SFM on the day of plating resulted in a dose-dependent reduction in the ET-induced stimulation of lactotrophs. These findings indicate that the presence of serum in culture medium alters the expression of cell properties underlying inhibitory and stimulatory responses to ET in terms of PRL secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630589 TI - Effects of sub-chronic treatment with chlordiazepoxide, buspirone and the 5-HT3 receptor antagonist, BRL 46470, on the social behaviour of mice. AB - Chlordiazepoxide (21.5 mg/l; 5 mg/kg daily), buspirone (12.8 g/l; 3.4 mg/kg daily) and the 5-HT3 receptor antagonist, BRL 46470, (40 micrograms/l; 10 micrograms/kg daily) were each given in the drinking fluid for 12-14 days to adult male CD1 mice. Controls received tap water. Effects of the treatments on behaviour during 5 min social encounters with untreated partners were examined by ethological procedures in an aversive and less aversive situation, an unfamiliar neutral cage and the home cage. In the neutral cage all compounds increased the occurrence of the social act, "nose" and enhanced digging of the unfamiliar sawdust, at the expense of exploration. In the home cage, all compounds increased social investigation and reduced non-social activity. The drug BRL 46470 evoked more marked effects on behaviour than did buspirone or chlordiazepoxide and in the neutral cage it enhanced some acts of aggression. These results show that all compounds increased reactivity to normal social and environmental stimuli, in addition to their anxiolytic profile of behavioural effects. PMID- 1630590 TI - Tianeptine increases the extracellular concentrations of dopamine in the nucleus accumbens by a serotonin-independent mechanism. AB - The effect of various doses of tianeptine on the extracellular concentrations of dopamine was studied in the striatum and nucleus accumbens of the rat. At 5 (but not 2.5) mg/kg intraperitoneally, tianeptine increased the extracellular dopamine only in the nucleus accumbens. At 10 mg/kg, the effect was also seen in the striatum but it was less marked and shorter-lasting. At 10 mg/kg (i.p.), tianeptine significantly raised the extracellular concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in both regions. The effect of 10 mg/kg tianeptine on dopamine and its metabolites was not significantly changed in animals which had received this dose twice daily for 15 days. Intracerebroventricular administration of 150 micrograms/20 microliters 5,7 dihydroxytryptamine, which markedly depleted serotonin in the brain, did not modify the effect of 10 mg/kg tianeptine on the extracellular concentrations of dopamine and HVA in the nucleus accumbens but reduced the effect on DOPAC. Various doses of tianeptine (1, 3 and 10 mg/kg i.p.) did not change the synthesis of serotonin and dopamine in the striatum and nucleus accumbens. The results show that tianeptine increased the extracellular concentrations of dopamine more in the nucleus accumbens than in striatum. The effect on the output of DA in the nucleus accumbens could be involved in the antidepressant activity of tianeptine. PMID- 1630591 TI - Effect of trimipramine on depolarization-induced and Na(+)-Ca2+ exchange-induced 45calcium uptake in synaptosomes from the cortex of the rat brain. AB - The present study examined the inhibition of synaptosomal uptake of 45calcium by racemic trimipramine and nortrimipramine and by enantiomers of trimipramine. Trimipramine, nortrimipramine, (+)-trimipramine and (-)-trimipramine inhibited the net K(+)-induced uptake of 45calcium with IC50 values of 31, 39, 17 and 95 microM, respectively. No significant difference could be detected between the parent compound trimipramine and the metabolite nortrimipramine; however, the levorotatory isomer had an IC50 value significantly larger than the dextrorotatory isomer. At normal therapeutic doses, a 25-40% inhibition of net K(+)-induced uptake of 45calcium, could be expected with trimipramine or 30-50% inhibition for trimipramine and nortrimipramine combined; these data, therefore, do not exclude the possibility that inhibition of voltage-dependent calcium channels could contribute to the therapeutic effect of trimipramine. The order of potency of stereoisomers of trimipramine, for inhibition of calcium channels, was the same as their reported order of potency in the clinic; this parallelism adds support to the possible involvement of blockade of calcium channels in the antidepressant effect. With respect to uptake of 45calcium induced by the Na(+) Ca2+ exchange process, all drugs inhibited this mechanism with a similar potency (IC50 74-91 microM); the drugs are not expected to have a significant effect on this exchange process, at therapeutic antidepressant doses. PMID- 1630592 TI - Flunarizine and R 56865 suppress veratridine-induced increase in oxygen consumption and uptake of 45Ca2+ in rat cortical synaptosomes. AB - The effect of the anti-ischemic compounds flunarizine and R 56865 on the veratridine-induced uptake of Ca2+ and Na+ was observed in cortical synaptosomes in the rat. The veratridine-induced uptake of Na+ and Ca2+ was determined by means of a measurement of synaptosomal oxygen consumption and a method for the uptake of 45Ca2+, respectively. Veratridine (10(-5) M) was found to induce a 3 fold increase in synaptosomal oxygen consumption (uptake of Na+) and uptake of 45Ca2+, both of which were inhibited by tetrodotoxin (10(-5) M). Nitrendipine (10(-5) M) and omega-conotoxin (5 x 10(-7) M) were ineffective on the veratridine induced response. Nimodipine (10(-5) M) suppressed the veratridine-induced uptake of 45Ca2+ but also diminished the unstimulated uptake of 45Ca2+. The veratridine induced uptake of Na+ was not influenced by nimodipine. Flunarizine (3 x 10(-6) 10(-5) M), as well as R 56865 (10(-6)-10(-5) M), attenuated the veratridine induced uptake of both Na+ and 45Ca2+. In conclusion, the veratridine-induced uptake of Na+ and 45Ca2+ was shown to be closely correlated to the activity of Na+ channels but not to voltage-operated Ca2+ channels. Secondly, flunarizine and R 56865 seemed to evoke their effects by interfering with the permeability of Na+ channels. Since veratridine-induced uptake of Na+ and Ca2+ shares some similarities with ischaemia-induced uptake of Na+ and Ca2+, it is proposed, that flunarizine and R 56865 exert their anti-ischaemic effects by reducing ischaemia induced Na+ and Ca2+ load, probably by inhibiting a TTX-sensitive Na+ channel. PMID- 1630593 TI - Electrophysiological evidence for a role of nitric oxide in prolonged chemical nociception in the rat. AB - The role of nitric oxide in the periphery and the spinal cord, during acute electrically-evoked and prolonged chemically-evoked nociceptive stimulation, was investigated in rats anaesthetised with halothane. The responses of single dorsal horn neurones to electrically-evoked A beta fibre and C fibre inputs were reduced by topical application (directly onto the spinal cord) of both the nitric oxide inhibitor, nitro-L-arginine methyl ester (L-NAME; 500-1500 micrograms) and the precursor of nitric oxide, L-arginine (4500 micrograms). Administration of L NAME, either directly into the receptive field (500-1500 micrograms) or intravenously (10-100 mg/kg) had little or no effect on the acute electrically evoked activity. Intravenous injection of L-NAME, administered 40 min prior to injection of formalin, significantly reduced the prolonged second peak of firing, with only a small effect on the short-duration first peak. Administration of L NAME, directly into the site of injection of formalin, as a 10 min pretreatment, significantly reduced the second but not the first peak of the response. Topical application of L-NAME onto the spinal cord, as a 30 min pretreatment, significantly reduced both the first and second peaks of the response. This inhibition was not reversed by the coadministration of L-arginine, which was inhibitory by itself. Thus, nitric oxide may be involved, in a complex way, in nociceptive events both in the periphery and within the spinal cord. PMID- 1630594 TI - Excitatory modulation by a spinal cholinergic system of a descending sympathoexcitatory pathway in rats. AB - Earlier studies have demonstrated that an excitatory cardiovascular response can be produced through activation of a spinal cholinergic system in rats. The present study was performed to determine whether this excitatory cardiovascular response was elicited through cholinergic potentiation of a descending spinal sympathoexcitatory pathway. Application of the cholinesterase inhibitor, neostigmine, directly to the surface of the spinal cord elicited increases in heart rate selectively when neostigmine was applied to upper thoracic segments (Th1-Th4), whereas all thoracic segments participated in the generation of the associated hypertensive response. The injection of a direct cholinergic agonist, carbachol, into an upper thoracic segment (Th2) produced tachycardic and pressor responses but only pressor responses when injected into a lower segment (Th11). Tachycardic responses occurred after injection of carbachol into the intermediolateral nucleus, a site between the intermediolateral nucleus and the central canal, the right lower dorsal horn and the ventral horn. At the Th11 level, carbachol increased blood pressure only when injected into sites between the intermediolateral nucleus and central canal. The pressor response, induced by electrical stimulation of the descending spinal sympathetic tract, was markedly potentiated at all stimulus strengths after intrathecal (i.t.) injection of neostigmine and this potentiation was antagonized by atropine. The accompanying tachycardic response to electrical stimulation was not affected when low stimulus strengths were employed but means increases in the heart rate, obtained in response to larger stimulus intensities, were eliminated after administration of neostigmine. These results are consistent with the presence of an intrinsic spinal cholinergic sympathoexcitatory pathway, possibly relegated to interneurons, which elicits cardiovascular responses, at least in part through potentation of descending sympathetic influences. PMID- 1630595 TI - Toxic effects of solstitialin A 13-acetate and cynaropicrin from Centaurea solstitialis L. (Asteraceae) in cell cultures of foetal rat brain. AB - Extracts of the aerial parts of the yellow star thistle (Centaurea solstitialis L.) were prepared using petroleum ether, chloroform and methanol and toxicity assessed in primary cell cultures of striatum, frontal cortex and mesencephalon, containing the substantia nigra or raphe nucleus from the brain of the foetal rat. Chloroform extracts significantly reduced the percentage of live cells whereas the petroleum ether extract was inactive. The ability of the methanol extract to reduce the percentage of live cells could not be distinguished from the effects of the vehicle controls for methanol. Subsequently, the plant material was extracted with dichloromethane and 10 fractions were obtained by column chromatography. Fractions 5, 6, 7 and 8 caused concentration-dependent cell death in the culture of substantia nigra, the other fractions were not toxic at the concentrations used. In further studies, solstitialin A was isolated from fraction 9, solstitialin A 13-acetate from fraction 6 and solstitialin A-3 acetate and cynaropicrin from fraction 7. Solstitialin A 13-acetate and cynaropicrin were toxic to cultures of substantia nigra cells. It is concluded that, of the compounds identified, solstitialin A 13-acetate and cynaropicrin have toxic potential in cell cultures, containing cells from the substantia nigra of the rat, the specificity of action to cells of the substantia nigra remains to be shown, and that a toxic action in the midbrain may contribute to the nigro pallidal encephalomalacia, caused by the ingestion of the yellow star thistle by horses. PMID- 1630596 TI - Learning and memory-enhancing effects of Ro 15-4513: a comparison with flumazenil. AB - Synthetic benzodiazepines produce an anterograde amnesia, which can be reversed by selective benzodiazepine antagonists or inverse agonists. It has therefore been suggested that the memory-enhancing effects of the antagonists are due to antagonism of an endogenous "benzodiazepine-like" endocoid. If the memory enhancing effects of the benzodiazepine antagonists are determined predominantly by the antagonism of such endogenous benzodiazepine-ligands, then it could be hypothesized that administration of an inverse agonist, which produces effects functionally opposite to those of benzodiazepine agonists, may also mimic the effects of benzodiazepine antagonists but not produce effects greater than those of the pure antagonists. The purpose of the present study was therefore to investigate the memory-enhancing effects of the benzodiazepine inverse agonist, ethyl-8-amido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5a] [1,4] benzodiazepine-3 carboxylate (Ro 15-4513) in young HSD:(ICR)BR mice and to compare these effects with those of the benzodiazepine antagonist, flumazenil. Pretraining injections of flumazenil and Ro 15-4513 (2.5 and 10.0 mg/kg) enhanced equally, both the acquisition and the retention of a task for 1 week requiring mice to discriminate the correct arm of a T-maze, to avoid a mild electric shock. Pretreatment with Ro 15-4513 also dose-dependently protected the animals from experimental amnesia, induced by the cholinergic receptor antagonist, scopolamine in a second model of memory, in which mice were required to passively avoid a dark chamber after shock. In contrast, Ro 15-4513, injected prior to daily active avoidance sessions, failed to significantly improve either the acquisition or retention performance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630597 TI - Behavioural effects of anatoxin, a potent nicotinic agonist, in rats. AB - Preliminary behavioural studies with the nicotinic agonist (+)-anatoxin have been carried with procedures sensitive to (-)-nicotine. In experimentally naive rats, (+)-anatoxin decreased locomotor activity; this effect resembled that of (-) nicotine, but it was not blocked by mecamylamine. In nicotine-tolerant rats, (+) anatoxin differed from (-)-nicotine because it did not increase locomotion. However, in rats trained to discriminate nicotine from saline in an operant conditioning procedure, (+)-anatoxin produced a partial nicotine-like discriminative stimulus effect that was blocked by mecamylamine, and a decreased rate of responding that was insensitive to mecamylamine. The behavioural profile of (+)-anatoxin differs from that of (-)-nicotine and it can be used for further investigations of CNS nicotinic receptors. PMID- 1630598 TI - Current bibliographies of neuropeptides prepared by the University of Sheffield Biomedical Information Service. PMID- 1630599 TI - Hyperthermia-induced seizures alter the levels of methionine-enkephalin in immature rat brain. AB - The effects of hyperthermia induced seizures on the amount of Methionine enkephalin (Met-E) in 15 day rat pups were examined. Animals exposed to an ambient temperature of 40 degrees C showed a gradual increase in body temperature reaching a maximum of 40.6 +/- 0.2 degrees C; at this time all of the animals had seizures. Elevated brain Met-E concentration was observed immediately after seizures. When the animals were exposed for 30 min to 27 degrees C environment maintained their normal body temperature throughout the experiments and no seizures were observed. The brain Met-E levels in this group were significantly lower than those observed in the animals exposed to 40 degrees C environment. These experiments suggest that enkephalinergic system may play a role in hyperthermia-induced seizures in the rat pups. PMID- 1630600 TI - Endogenous opioid peptides in brain and pituitary of rats with absence epilepsy. AB - The level of opioid peptides in several brain areas and in the pituitary was estimated in WAG/Rij rats, which are considered to be a genetic animal model for human absence epilepsy. In comparison with three groups of non-epileptic controls, these epileptic rats had an elevated level of the proenkephalin-derived peptide Met-enkephalin-Arg6-Gly7-Leu8 in the mesencephalon and striatum, while the level of the prodynorphin-derived peptide alpha-neoendorphin was increased in the striatum and hippocampus. In addition various age- and/or strain-related changes in these peptide levels were found in the hippocampus, thalamus, striatum, frontal cortex and neurointermediate lobe of the pituitary. No difference in the hypothalamic beta-endorphin level were found between epileptic and non-epileptic rats, though strain- and/or age-related changes in the peptide content were detected in both lobes of the pituitary. The increased level of proenkephalin and prodynorphin opioid peptides in brain structures, essential for the appearance of spike-wave discharges, suggests that these opioid systems, but not proopiomelanocortin one, may play a role in absence epilepsy. PMID- 1630601 TI - The behavioural effects of neuropeptide Y (NPY) injection into the rat brain frontal cortex. AB - The aim of this study was to investigate the influence of intracortical administration of neuropeptide-Y on the behaviour of rats. One week before the behavioural test the frontal cortex of rats was chronically implanted with intracerebral cannulae. Neuropeptide-Y (or saline in the control group) was injected in a volume of 1 microliter. After treatment the behaviour of the rats was tested in an open field apparatus and a light-beam actometer. The number of line crossings, episodes of rearing, sniffing, washing and head poking were counted. The results indicate that administration of neuropeptide-Y to the frontal cortex of rats slightly increased exploratory and locomotor activity. PMID- 1630602 TI - Inhibitory effect of D-myo-inositol-1,2,6-trisphosphate on glucose-stimulated insulin secretion in the mouse. AB - It has been demonstrated that D-myo-inositol-1,2,6-trisphosphate (PP56) antagonizes the effect of neuropeptide Y (NPY) in guinea pig basilar arteries. NPY is known to inhibit insulin secretion. We therefore examined whether PP56 is a NPY antagonist also on insulin secretion. Unanaesthetized mice were injected intraperitoneally with PP56. It was found that the plasma insulin response to a subsequent intravenous glucose challenge (500 mg/kg) was inhibited by PP56 at 20 but not at 2 mg/kg. Also NPY (8.5 nmol/kg) inhibited the glucose-induced increase in plasma insulin levels. When given together, PP56 and NPY exerted additive inhibitory effect. Thus, PP56 is not a NPY-antagonist on insulin secretion, but rather exerts a NPY-like effect. Furthermore, in isolated mouse islets, PP56 at 100 nmol/l, but not at lower dose levels, inhibited glucose (11.1 mM)-stimulated insulin secretion. Hence, PP-56 inhibits glucose-stimulated insulin secretion by a direct effect on the pancreatic islets. PMID- 1630603 TI - Cholecystokinin (CCK)-like material and CCK mRNA levels in the rat brain and spinal cord after acute or repeated morphine treatment. AB - The effects of a single or repeated administrations of morphine on the tissue levels of cholecystokinin-like material (CCKLM) and pre pro cholecystokinin mRNA (CCK mRNA) were examined in various brain and spinal cord regions (cerebral cortex, cerebellum, hippocampus, septum, substantia nigra, lumbar enlargement) in adult rats using a specific radioimmunoassay and 'Northern blot' analysis, respectively. Although a clear parallelism existed between the regional distribution of CCKLM (septum greater than cerebral cortex greater than or equal to hippocampus much greater than lumbar enlargement, dorsal zone greater than substantia nigra greater than lumbar enlargement, ventral zone much much greater than cerebellum) and that of CCK mRNA, some mismatch was found notably in the septum where CCK mRNA levels were less than in other regions except the cerebellum. Neither CCKLM nor CCK mRNA levels were altered one hour after an acute administration of morphine (5 mg/kg i.p.). Similarly, morphine addiction after a four-day treatment with this drug was not associated with any change in the tissue levels of CCKLM and CCK mRNA. These data indicate that the previously reported modulatory action of opioids on central CCKergic systems could occur without affecting the preproCCK gene transcription and the tissue peptide concentrations. PMID- 1630604 TI - Diffuse "fibrillary" astrocytomas: correlation of MRI features with histopathologic parameters and tumor grade. AB - MR images in 54 patients with biopsy-proven diffuse or "fibrillary" astrocytomas were analyzed and compared with the histopathologic features in order to determine which histopathologic characteristics underlie the radiographic findings in these gliomas and whether radiographic findings are more closely correlated with individual histopathologic characteristics than with histologically determined tumor grade. The MRI features studies included tumor heterogeneity, edema, mass effect, border sharpness, "anatomic invasion", contrast enhancement, hemorrhage, and the presence of flow voids, calcium and cyst formation. The histopathologic characteristics studied included cellular atypia, mitoses, cellularity, endothelial proliferation, necrosis and tumor grade. Edema (P less than 0.01), flow voids (P = 0.02) and contrast enhancement (P less than 0.01) demonstrated a direct correlation with tumor grade, but edema (P less than 0.01) and contrast enhancement (P less than 0.01) also demonstrated a significant correlation to tumor cellularity. Tumor heterogeneity was associated with the presence of necrosis (P = 0.01). Hemorrhage occurred only in high grade tumors, where it correlated with endothelial proliferation (P = 0.04). PMID- 1630605 TI - Trigeminal neuromas: assessment of MRI and CT. AB - We report four cases of trigeminal neuroma. One of the patients had von Recklinghausen's neurofibromatosis with plexiform neurofibromas of the branches of the trigeminal nerve. MRI provided more information than CT as regards the spread of tumour: extension to the mandibular and maxillary division of the trigeminal nerve was well demonstrated on sagittal and coronal sections. This examination yielded an accurate census of the intraocular plexiform neurofibromas and allowed a correct preoperative diagnosis to be obtained. With Gd-DOTA, better definition of the outline of the tumours and of cystic components was obtained. However, CT was better for demonstration of bone erosions. PMID- 1630606 TI - Contrast behavior between microadenoma and normal pituitary gland after gadolinium injection as a function of time at 1.5 T. AB - The behavior of contrast enhancement between a microadenoma and the normal pituitary gland after gadolinium injection was evaluated in 12 operatively confirmed cases using a repetitive sequence of four coronal T1-weighted spin echo series (T1 SE) (continuous acquisition, TR = 400 ms), followed by conventional coronal T1 SE (TR = 600 ms) and a three-dimensional fast low-angle shot sequence. The first and second acquisitions were useful with respect to delayed scans only in 3 cases (25%). Nevertheless, in these cases confident diagnosis could also be made on pre-contrast studies, which diminishes the real advantage of this finding. For a 1.5 T MRI unit we advocate starting with coronal T1 SE 30 s after a rapid injection of gadolinium. PMID- 1630607 TI - Radiological study of the brain at various stages of human immunodeficiency virus infection: early development of brain atrophy. AB - One hundred and one persons infected with human immunodeficiency virus (HIV-1), in whom other central nervous system infections or diseases were excluded, underwent brain CT and/or MRI at various stages of HIV-1 infection: 29 were asymptomatic (ASX), 35 had lymphadenopathy syndrome (LAS), 17 had AIDS-related complex (ARC), and 20 had AIDS. A control group of 32 HIV-1-seronegative healthy persons underwent brain MRI. The most common finding was brain atrophy, found in 9% of controls, and 31% of ASX cases, 29% of LAS, 59% of ARC and 70% of AIDS. Even the difference between the ASX or LAS groups and controls was significant. The changes were bilateral and symmetrical, and they were more severe at later stages of infection. Infratentorial atrophy was seen in the early stages; supratentorial atrophy became more pronounced at ARC, and generalized atrophy was typical of AIDS. Non-specific small hyperintense foci were found on MRI in 13% of controls and 6-15% of the infected groups. Larger, diffuse, bilateral white matter infiltrates were detected in 4 demented patients with AIDS. Four patients with AIDS and 1 with LAS had focal hyperintense lesions in the internal capsules, lentiform nuclei or thalamus, often bilateral on MRI. One patient with AIDS, examined with CT only, had low density in the lentiform nucleus. Loss of brain parenchyma can occur at an early stage of HIV-1 infection, and the atrophic process becomes more intense at later stages (ARC and AIDS). Parenchymal infiltration, seen as hyperintense areas on MRI, is most often associated with severe clinical symptoms, in the later stages of the disease. PMID- 1630608 TI - Locations of cerebral infarctions in tuberculous meningitis. AB - The locations of cerebral infarctions were studied in 14 patients with tuberculous meningitis (TBM) and 173 patients with noninflammatory ischemic stroke (IS). In patients with TBM, 75% of infarctions occurred in the "TB zone" supplied by medial striate and thalamoperforating arteries; only 11% occurred in the "IS zone" supplied by lateral striate, anterior choroidal and thalamogeniculate arteries. In patients with IS, 29% of infarctions occurred in the IS zone, 29% in the subcortical white matter, and 24% in (or involving) the cerebral cortex. Only 11% occurred in the TB zone. Bilaterally symmetrical infarctions of the TB zone were common with TBM (71%) but rare with IS (5%). PMID- 1630609 TI - Late CT manifestations in spontaneous putaminal haemorrhage. AB - Serial CT studies were performed on 61 patients with putaminal haemorrhage, to determine outcome. The average duration of the follow-up was 2 years and 5 months. Several types of late CT change were identified, including disappearance of the haematoma without a trace of haemorrhage, a residual cavity, deformity of the lateral ventricle, atrophy of the head of the caudate, white matter degeneration and linear pseudocalcification around the cavity. Small haematomas, comma-shaped and less than 2 cm wide might disappear without leaving any trace. A slit or small rounded residual cavity was a frequent result of elliptical or irregular haematomas with little mass effect. With prominent ventricular compression, there were distortion and dilatation of the lateral ventricle and atrophy of the head of the caudate nucleus, which might be accompanied by white matter degeneration and pseudocalcification around the cavity. Five cases (8%) were left with no trace of previous haemorrhage, 32 (52%) with a slit cavity, 10 (16%) with a small round cavity, 8 (13%) with a large cavity, 5 (8%) with no residual cavity but with ventricular deformity, and 1 (3%) with only pseudocalcification at the site of the haemorrhage. PMID- 1630610 TI - Pure sensory stroke resulting from thalamic haemorrhage. AB - Pure sensory stroke has not previously been reported with thalamic haemorrhage and had indeed been considered to exclude cerebral haemorrhage. We describe a case of thalamic haemorrhage causing a pure sensory stroke and propose that we should bear in mind the possibility of haemorrhage in such cases. PMID- 1630611 TI - Dilatation of the temporal horn in subarachnoid haemorrhage. AB - CT studies of 50 patients with spontaneous subarachnoid haemorrhage (SAH) and 100 randomly selected patients were reviewed with regard to the size of the frontal and temporal horns of the lateral ventricles. The temporal horn was classified into four grades, based on the size of its posterior portion at the level of the midbrain. The horn was clearly visible in 66% of patients with SAH, but in only 2% of controls. In the SAH group, the temporal horn tended to dilate sooner than the frontal horn after haemorrhage and could be seen clearly in a larger proportion of patients. Thus, assessment of the size of the temporal horn appears to be a simple and sensitive method for assessing ventricular dilatation. In addition, dilatation of the temporal horn may prove to be an important indirect sign suggesting SAH in patients in whom no high density clot is seen on CT. PMID- 1630612 TI - Alexia without agraphia. AB - Two new cases of alexia without agraphia are presented. Pertinent clinical findings, anatomy, pathophysiology and differential diagnoses are reviewed. The importance of carefully examining the inferior portion of the left side of the splenium of the corpus callosum on CT and/or MR scans in patients who present with this clinical syndrome is stressed. PMID- 1630613 TI - The reversal sign. AB - We report a 36-year-old woman with a bacterial meningitis. CT after resuscitation showed a striking "reversal sign." Opinions on the pathogenesis of this sign are discussed; it indicates serious brain damage and carries a poor prognosis. PMID- 1630614 TI - Variability in the enhancement of the normal central skull base in children. AB - We studied the signal and enhancement characteristics of the central skull base prospectively in 40 children aged 13 days to 8 years, on a 1.5 T MRI system. Identical standard short TR/TE spin echo sequences in the sagittal plane were performed before and after intravenous gadolinium-DTPA. The sequences used for comparison were filmed at identical window and level settings. Three independent observers assessed (1) the intensity of contrast enhancement of the basisphenoid, basiocciput and presphenoid, (2) the signal intensity of the spheno-occipital synchondrosis, (3) the degree of pneumatization of the sphenoid sinus and (4) the uniformity of signal intensity reflecting fatty replacement of the marrow of the basisphenoid, basiocciput and presphenoid. In 16% and 28% respectively of cases there was no enhancement of the basisphenoid and basiocciput after gadolinium administration; in 42% and 44% there was mild enhancement, and moderate or intense enhancement was observed in 42% and 28% of cases. Even when there was irregular fatty replacement, residual hemopoietic clements could enhance intensely. When skull base neoplasms are being investigated, the normal signal irregularity and enhancement of the central skull base in children must not be confused with pathologic invasion of the marrow. PMID- 1630616 TI - MRI demonstration of Kernohan's notch: case report. AB - We report a left acute subdural haematoma caused by rupture of a left anterior cerebral artery aneurysm, which progressed to left hemiparesis. Coronal MRI was superior to CT for visualizing Kernohan's notch. PMID- 1630615 TI - Atypical MR presentation of Wilson disease: a possible consequence of paramagnetic effect of copper? AB - A 53-year-old patient with Wilsons's disease and without autonomic dysfunction presented on T2-weighted MR study an atypical decreased signal intensity of the putamina and the caudate nuclei. Possible explanations of such a signal abnormalities are discussed. PMID- 1630617 TI - Pineal teratocarcinoma with drop metastases: MR features. AB - In a rare case of teratocarcinoma of the pineal gland, MRI accurately depicted the primary tumor and diffuse enhancing drop metastases along the surface of the brain stem and the spinal cord. PMID- 1630618 TI - Diffusion of contrast media in cerebrospinal fluid: comparison of iohexol, iopamidol and iotrolan in vitro. AB - Diffusion of iohexol (300 and 240 mgI/ml), iopamidol (300 and 200 mgI/ml), and iotrolan (300 and 240 mgI/ml) in the cerebrospinal fluid (CSF) of 16 patients was studied in vitro. Test tubes containing CSF were kept in a waterbath at 37 degrees C. Contrast medium was injected along the wall into the tubes, and diffusion of contrast media in the tubes was followed with repeated computed tomography for 5 h. The contents of the tubes were then mixed by shaking, and the tubes were scanned immediately and 8 h later. The contrast media first settled in the bottom of the tubes and then diffused upwards. Iotrolan diffused more slowly than the other media, but the difference was only significant at a concentration of 300 mgI/ml. The difference between iohexol and iopamidol was minimal. In general, diffusion was slower in CSF samples with an elevated protein content, but the difference in the diffusion of contrast medium in normal and pathological CSF was seldom statistically significant, perhaps owing to the small number of samples (5) with an elevated protein content. All contrast medium-CSF mixtures remained homogeneous after mixing. These experiments showed measurable differences in the diffusion of contrast media in CSF, but it does not seem very likely that these would be significant in clinical practice. PMID- 1630619 TI - Radicular avulsion resulting from spinal injury: assessment of diagnostic modalities. AB - The diagnostic utility of imaging techniques in injuries to the intramedullary and subarachnoid portions of the brachial plexus, with possibly complete avulsion of one or more nerve roots from the spinal cord and extramedullary meningocoele was compared in 18 patients studied by unenhanced computed tomography (CT), cervical myelography, myelographic CT (MCT) and magnetic resonance imaging (MRI). Emphasis was placed on the lesions of the subarachnoid roots. CM was the only diagnostic modality to show avulsion of 18 nerve roots and their levels in 8 patients (100% = gold standard), and to verify 2 incomplete avulsions. MCT reliably revealed 8 of 18 (45%) and MRI 1 out of 18 (6%) avulsions. Myelography with MCT showed intact subarachnoid nerve roots in 10 additional patients. MRI and MCT (16 out of 16 = 100%) were superior to myelography (14/16 = 88%) for demonstrating 16 traumatic meningocoeles in 8 patients; follow-up MRI (6-24 months) showed no increase in their size. We recommend a subsequent CT to role out fracture to the spinal column; MRI should provide significant information concerning oedema or haemorrhage in the spinal cord. Myelography with segmental MCT is performed to differentiate pre- from post-ganglionic lesions, data which are essential for deciding whether exploration of the plexus or a motor substitution operation is indicated. PMID- 1630620 TI - Sparganosis in the spinal canal with partial block: an uncommon infection. AB - A case of rare intraspinal sparganosis treated by surgical excision is described. In this 59-year-old male with paraparesis and voiding problem, an intradural mass was noted on myelogram. Magnetic resonance (MR) and computed tomographic appearance of spinal and associated cerebral lesion are illustrated and possible route of migration discussed. This represents, to our knowledge, the first MRI demonstration of intraspinal sparganosis reported in the literature. PMID- 1630621 TI - Balloon occlusion of the internal carotid artery in 40 cases of giant intracavernous aneurysm: technical aspects, cerebral monitoring, and results. AB - We have studied the results of carotid occlusion in the treatment of giant intracavernous carotid artery (ICA) aneurysms in 40 patients. Clinical, angiographic, Doppler and cerebral blood flow (CBF) criteria for tolerance of occlusion are discussed. The patients had headaches (47.5%), cranial nerve compression (87.5%), decreased visual acuity (20%), ruptured aneurysm (15%) and 5% were asymptomatic. Balloon occlusion tests were performed under light sedation anaesthesia: a successful test required perfect clinical tolerance and adequate angiographic collateral circulation in arterial, parenchymatous, and venous phases. Additional criteria included xenon 133 CBF measurements, and transcranial Doppler sonography of the middle cerebral artery. According to these criteria, 5 patients did not tolerate test occlusion and required an extra-intracranial (EC IC) bypass. Mean follow-up was 4.7 years. All patients were radiologically cured of their aneurysm, and in 35 the symptoms resolved, although 3 had persistent ocular motor nerve palsies, and in 4 visual defects were unchanged. Complications were 1 permanent and 3 transient neurological deficits. Balloon occlusion of the ICA is an effective, reliable form of treatment for intracavernous giant aneurysm and should replace surgical ligation of the cervical carotid artery. With CBF or Doppler monitoring, the risk of neurological deficit is diminished. EC-IC bypass prior to ICA occlusion is indicated if test occlusion is not tolerated. PMID- 1630622 TI - Platinum coil treatment of complex aneurysms of the vertebrobasilar circulation. AB - Two patients with complex aneurysms of the vertebrobasilar system were treated using platinum coils. During these sessions, 22 coils were placed in a basilar tip aneurysm in a 48-year-old woman. Almost total occlusion of the lumen was achieved, excepted in the area from which the right posterior cerebral artery arose. A large fusiform vertebral artery aneurysm in a 6-year-old boy was treated using 16 coils, which partially occluded the lumen at initial embolization. Follow-up angiography 2 weeks later revealed almost complete occlusion of the lumen with preservation of the vertebral artery. Our experience indicates that coil embolization of complex intracranial aneurysms is an acceptable treatment alternative to surgery or to a detachable balloon. PMID- 1630623 TI - Phosphorylation of Alzheimer amyloid precursor protein by protein kinase C. AB - The beta/A4 amyloid precursor protein is a membrane protein with one transmembrane domain. The accumulation and deposition of beta/A4 amyloid protein in Alzheimer's disease is thought to be brought about by altered processing of beta/A4 amyloid precursor protein. Activation of protein kinase C and/or inhibition of protein phosphatases 1 and 2A results in an increase in the proteolytic processing and secretion of beta/A4 amyloid precursor protein. These effects might result either from phosphorylation of beta/A4 amyloid precursor protein by protein kinase C or from phosphorylation of components of the beta/A4 amyloid precursor protein processing apparatus. We have previously reported phosphorylation by protein kinase C of a synthetic peptide corresponding to part of the cytoplasmic domain of beta/A4 amyloid precursor protein. However, it was not known whether beta/A4 amyloid precursor protein holoprotein was phosphorylated in its native conformation in the cell membrane. Using a PC12 (rat pheochromocytoma) semi-intact cell system, we now report that mature isoforms of beta/A4 amyloid precursor protein are phosphorylated by protein kinase C at Ser655. Five COOH-terminal fragments which are generated by processing of mature beta/A4 amyloid precursor protein were also phosphorylated by protein kinase C at Ser655. The results support the idea that the beta/A4 amyloid precursor protein haloprotein is a physiological substrate for protein kinase C. These observations should facilitate our understanding of the relationship between altered protein phosphorylation and beta/A4 amyloid production. PMID- 1630624 TI - Restoration of learning ability in fornix-transected monkeys after fetal basal forebrain but not fetal hippocampal tissue transplantation. AB - Monkeys with bilateral transection of the fornix were severely but selectively impaired on learning and retention of visuospatial conditional discriminations, visual conditional discriminations and non-conditional spatial-response tasks. Bilateral transplantation of cholinergic-rich fetal basal forebrain tissue into the hippocampus abolished significant learning impairments on all those tasks impaired by fornix lesions when tested three to nine months after transplantation whereas bilateral transplants of non-cholinergic fetal hippocampal tissue into hippocampus showed no such beneficial effect. Acetylcholinesterase staining was severely depleted throughout the dentate gyrus and hippocampus in fornix transected monkeys compared with animals with control corpus callosum ablations. Staining was largely restored to normal in the host hippocampus and dentate gyrus in monkeys with cholinergic transplants, whereas acetylcholinesterase staining was abnormal in those with non-cholinergic grafts. These experiments suggest that where a "higher order" cognitive function, in this case the acquisition of specific types of information into long-term memory, is disturbed by a neuropharmacologically simple lesion, cognitive function can be restored by transplantation of neurons containing appropriate neurotransmitters. PMID- 1630625 TI - Alterations in the properties of hippocampal pyramidal neurons in the aged rat. AB - The electrophysiological and pharmacological properties of CA1 hippocampal pyramidal neurons were studied in slices from young (three to four months) and aged (25-32 months) Sprague-Dawley rats having previously performed two behavioral tasks. About 20% of the aged rats were impaired in either the spontaneous alternation task or the water maze task. Electrophysiological parameters were measured and compared in young and aged animals using intracellular recordings. No age-related differences were observed in membrane potential, input resistance, amplitude of action potentials or amplitude of calcium spikes. The amplitude and duration of individual afterhyperpolarizations following a single spike were unchanged. In contrast, the neuronal excitability was significantly decreased and the spike duration significantly enhanced in aged rats as compared to young rats. The comparison of afterhyperpolarizations (which follow a burst of spikes) between young and aged rats was more complex. An increase in the amplitude and duration of afterhyperpolarizations generally occurred in aged animals. However, this increase was not consistent among animals and was dependent on the holding potential of the neuron and on the number of action potentials used to trigger the afterhyperpolarization. The depolarizing effect of bath-applied carbachol, as well as the associated increase in membrane resistance were reduced in neurons from aged rats. In contrast, the effects of carbachol on the depression of synaptic events and the blockade of the afterhyperpolarizations were similar in young and aged animals. In addition, the amplitude of the slow cholinergic excitatory postsynaptic potential induced by stimulation of cholinergic afferents in the presence of physostigmine was also decreased in aged rats. Excitatory postsynaptic potentials and inhibitory postsynaptic potentials following electrical stimulation of stratum radiatum were compared. The amplitude and duration of excitatory postsynaptic potentials were increased in aged rats. The amplitude and duration of the fast inhibitory postsynaptic potential were not significantly affected in aged animals. In contrast, the duration of the slow inhibitory postsynaptic potential was decreased in aged rats. Since the mean baclofen-induced hyperpolarization was only slightly reduced in aged rats, the most likely explanation is a decrease in the release of GABA rather than an alteration in the postsynaptic response mediated by GABAB receptors. A statistically significant correlation was found between the degree of impairment in the spontaneous alternation task and the amplitude of the carbachol-induced depolarization. PMID- 1630626 TI - Hypoxia produces cell death in the rat hippocampus in the presence of an A1 adenosine receptor antagonist: an anatomical and behavioral study. AB - Endogenous adenosine depresses synaptic transmission in rat hippocampal slices during periods of hypoxia, a potentially neuroprotective cellular response that is attenuated by the adenosine antagonist 8-cyclopentyltheophylline. In this study, rats were exposed to moderate hypoxic conditions (5% O2- 95% N2, 40 min x three days) in the presence or absence of 8-cyclopentyltheophylline, and the effects of reducing adenosinergic inhibition during hypoxia were assessed histologically and behaviorally. Half the rats exposed to low levels of oxygen in the presence of 8-cyclopentyltheophylline (10 mg/kg) suffered unilateral or bilateral hippocampal damage largely limited to the CA1 subfield. Animals which had suffered hippocampal damage were also impaired in their performance of a working memory version of the Morris Water Maze, but not a passive avoidance task (step-through). Hypoxia alone did not result in neuronal damage or behavioral impairment. These results provide further evidence that endogenous adenosine provides an important level of neuronal protection during even prolonged periods of hypoxia. PMID- 1630628 TI - Background firing activity in guinea-pig neocortex in vitro. AB - The background firing activity was recorded extracellularly in experiments on guinea-pig neocortical slices maintained in vitro. The following types of background firing activity were revealed: (i) high regular single spikes (48%), (ii) irregular single spikes (15%), (iii) bursts (7%), (iv) groups (7%), (v) mixed activity where single spikes alternated with bursts or groups (28%). The specific interspike interval distribution and the specific shape of autocorrelogram corresponded to each of these background firing activity types. Furie analysis of autocorrelograms showed periodic components in spike sequences with the maxima at 3, 12, and 28 Hz. When blocking synaptic transmission with 100 mM adenosine, about 70% of the background active cells "fell silent" and the remaining 30% of neurons continued to generate action potentials. The latter seem to be actual spontaneously active neurons, i.e. they were capable of autonomous spike generation. We failed to find any correlation between the type of neuronal firing and the ability of neurons to be spontaneously active. The selective blockade of inhibitory synapses with 100 mM picrotoxine did not practically change the character of background firing activity though the responses to stimulation became epileptic. An important conclusion to emerge from this study is that the background firing activity in cortical slices can include the actual spontaneous discharges related to intrinsic cell properties as well as those concerned with synaptic actions. Furthermore, a small number of spontaneously active neurons seem to be able to synaptically activate twice the number of cells. The inhibitory interneurons did not significantly influence the propagation of excitation with the absence of stimulation. PMID- 1630627 TI - Acute systemic heat stress increases glial fibrillary acidic protein immunoreactivity in brain: experimental observations in conscious normotensive young rats. AB - The possibility that astrocytes participate in the pathophysiology of thermal brain injury caused by systemic heat exposure was examined in conscious young rats. The temporal and regional pattern of the astrocytic response to thermal injury was characterized by demonstrating the immunoreactivity of glial fibrillary acidic protein (GFAP) using monoclonal antibody and avidin-biotin complex technique. Exposure of conscious young animals to heat at 38 degrees C for 4 h in a biological oxygen demand incubator resulted in a marked increase of the GFAP immunoreactivity in specific brain regions as compared with the intact controls. The intensity of the increased GFAP immunoreactivity was mainly noted in pons, medulla and cerebellum, followed by thalamus, hypothalamus, hippocampus and caudate nucleus. The cerebral cortex of heat-exposed animals showed only a mild increase in GFAP immunoreactivity which was predominantly concentrated in cingulate, parietal and pyriform cortices. The immunostaining in general was seen in the perivascular glia, within the neuropil and the glia limitans. This increase in GFAP immunoreactivity was absent in animals exposed to the same ambient temperature (38 degrees C) for 1 h and 2 h, or at a lower temperature (36 degrees C) for 4 h. These results show that (i) astrocytes actively participate in the pathophysiology of heat stress, (ii) endogenous thermal brain injury elicits activation and hypertrophy of astrocytes ("reactive gliosis") depending on the magnitude and duration of the ambient heat stimulus, and (iii) the astrocytic reaction (observed as increased GFAP immunostaining) could be induced much more rapidly within a very short survival period of 4 h, not reported earlier. PMID- 1630629 TI - Hypothalamic, dorsal raphe and external electrical stimulation modulate noxious evoked responses of habenula neurons. AB - Extracellular recording techniques were used to investigate the effects of focal brain stimulation and external electrical stimulation on spontaneous activity and on noxious evoked responses in the habenular nucleus of anesthetized Sprague Dawley rats. Two hundred and forty-one habenular neurons were tested to noxious and non-noxious stimuli. The habenular neurons exhibited three cell types according to their patterns of response to the noxious stimulus: 123 neurons (51%) responded to noxious stimulus by excitation and were classified as "nociceptive-on" cells; 56 neurons (23%) responded to the same noxious stimulus by decreasing their firing rate and were classified as "nociceptive-off" cells; and 62 neurons (26%) failed to respond to noxious stimulation and were classified as "non-nociceptive" cells. None of these 241 cells responded to non-noxious stimulus. One hundred and fifty-five, 160, 142 and 241 habenular neurons were tested following focal lateral hypothalamus stimulation, dorsal raphe stimulation, cerebellar stimulation and transcranial electrical stimulation alone and concomitant with noxious stimulation, respectively. The observations demonstrate that focal lateral hypothalamic, dorsal raphe and external (transcranial) electrical stimulation suppresses habenular noxious evoked responses while cerebellar electrical stimulation elicits no effect on the nociceptive-off cells and augmenting effects on the nociceptive-on cells. In addition, it was observed that low current (below threshold) external transcranial electrical stimulation was as effective in suppression of habenular noxious evoked responses as was focal brain electrical stimulation in the lateral hypothalamus and dorsal raphe. PMID- 1630630 TI - Depolarization of rat locus coeruleus neurons by adenosine 5'-triphosphate. AB - Intracellular recordings were performed in a pontine slice preparation of the rat brain containing the locus coeruleus. The enzymatically stable P2-purinoceptor agonist alpha,beta-methylene ATP increased the firing rate without altering the amplitude or shape of action potentials; the afterhyperpolarization following a spike was not changed either. When locus coeruleus neurons were hyperpolarized by current injection in order to prevent spontaneous firing, alpha,beta-methylene ATP produced depolarization and a slight increase in the apparent input resistance. A combined application of kynurenic acid and bicuculline methiodide failed to alter the alpha,beta-methylene ATP-induced depolarization, and tetrodotoxin only slightly depressed it. A gradual shift of the membrane potential by hyperpolarizing current injection led to a corresponding decrease, but no abolition or reversal of the alpha,beta-methylene ATP effect. In the hyperpolarized region, the current-voltage curve of alpha,beta-methylene ATP came into close approximation with, but did not cross, the control curve. Elevation of the external K+ concentration, or the intracellular application of Cs+ by diffusion from the microelectrode, depressed the response to alpha,beta-methylene ATP; external tetraethylammonium was also inhibitory. External Ba2+ and Cs+ had no effect or only slightly decreased the alpha,beta-methylene ATP-induced depolarization. A low Na+, or a low Ca2+ high Mg2+ medium, as well as the presence of Co2+ in the medium, markedly reduced or even abolished the depolarization by alpha,beta-methylene ATP. ATP itself did not produce consistent changes in the membrane potential or input resistance. However, in the presence of the P1-purinoceptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, ATP consistently increased the firing rate and evoked an inward current. In conclusion, P2-purinoceptor activation appears to depolarize locus coeruleus neurons by inhibiting a persistent potassium current, and at the same time opening calcium-sensitive sodium channels or calcium-sensitive non-selective cationic channels. PMID- 1630631 TI - The partial inhibition of inflammatory responses induced by capsaicin using the Fab fragment of a selective calcitonin gene-related peptide antiserum in rabbit skin. AB - The effect of an anti-calcitonin gene-related peptide (CGRP) antibody on responses induced by the sensory C-fibre neuropeptide, CGRP, and capsaicin, which selectively activates C-fibre nerves, was investigated in rabbit skin. Test agents and antibody were injected intradermally. Local blood flow changes were measured by 133Xenon clearance and oedema formation by [125I]albumin accumulation. Preinjection intradermally with the Fab fragment of a goat anti human alpha CGRP antibody selectively inhibited increased blood flow induced by CGRP (3 x 10(-12) mol/site) and caused a partial, but significant inhibition of increased blood flow induced by capsaicin (3 x 10(-7) mol/site). Oedema induced by histamine and bradykinin was potentiated by vasodilator doses of CGRP and capsaicin. These potentiating effects were significantly inhibited by pretreatment with anti-CGRP Fab. The Fab fragment was more potent in inhibiting capsaicin-induced responses than the parent IgG. These results suggest that capsaicin releases vasodilator quantities of CGRP in rabbit skin. PMID- 1630632 TI - c-fos expression in rat lumbar spinal cord during the development of adjuvant induced arthritis. AB - A parallel clinical and behavioral study of adjuvant-induced arthritis in the rat showed four stages in the time-course of the disease: preclinical (first week), acute (weeks 2-4), post-acute (weeks 5-8) and recovery weeks 9-11) [Calvino et al. (1987) Behav. Brain Res. 24, 11-29]. As several studies have reported the expression of the proto-oncogene c-fos in spinal cord neurons following acute noxious peripheral stimuli, the aim of this study was to quantitatively assess Fos-like immunoreactivity in lumbar spinal cord neurons at various times of adjuvant-induced arthritis development, i.e. one, two, three, 11 and 22 weeks post-inoculation. The total number of Fos-like immunoreactive neurons in the lumbar enlargement correlated with the observed development of adjuvant-induced arthritis, i.e. Fos-like immunoreactivity was absent at one week, moderate at two weeks, greatly increased at three weeks, decreased at 11 weeks and returned to control values at 22 weeks. At three weeks, at the peak of Fos-like immunoreactivity distribution and acute stage of hyperalgesia, maximal labeling was observed in L3 and L4 spinal segments. In these segments, the most densely labeled region was the neck (laminae V and VI) of the dorsal horn (55%) and the ventral horn (35%) as compared to the superficial laminae (laminae I and II; 5%) and the nucleus proprius (laminae III and IV; 5%). These data indicate that c-fos expression induced by chronic inflammation is better expressed in deeper laminae than in the superficial ones, and that the number of Fos-positive cells correlates with behavioral studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630633 TI - Localization of dystrophin and dystrophin-related protein at the electromotor synapse and neuromuscular junction in Torpedo marmorata. AB - The immunological identification of dystrophin isoforms at the neuromuscular junction and Torpedo marmorata electromotor synapse was attempted using various antibodies. A polyclonal antibody raised against electrophoretically purified dystrophin from T. marmorata electrocyte has been thoroughly investigated. This antibody recognized dystrophin in the electric tissue as well as sarcolemmal and synaptic neuromuscular junction dystrophin in all studies species (T. marmorata, rat, mice and human) at serum dilutions as high as 1:10,000. At variance, no staining of either the sarcolemma or neuromuscular junction was observed in Duchenne muscular dystrophy or mdx mice skeletal muscles. In these muscles, other members of the dystrophin superfamily, in particular the dystrophin-related protein(s) encoded by autosomal genes are present. These data thus demonstrate the specificity of our antibodies for dystrophin. Anti-dystrophin-related protein antibodies [Khurana et al. (1991) Neuromusc. Disorders 1, 185-194] which gave a strong immunostaining of the neuromuscular junction in various species, including T. marmorata, cross-reacted weakly with the postsynaptic membrane of the electrocyte. Taken together, these observations are in favor of the existence of a protein very homologous to dystrophin at the electromotor synapse in T. marmorata, whereas both dystrophin and dystrophin-related protein co-localize at the neuromuscular junction as in all species studied. The electrocyte thus offers the unique opportunity to study the interaction of dystrophin with components of the postsynaptic membrane. PMID- 1630634 TI - The neurology of sleep. PMID- 1630635 TI - Neuroanatomic and neurologic correlates of sleep disturbances. AB - The cyclic alternations of wakefulness and sleep competing for the domain of brain activity are controlled by neuronal systems contained in the core of the brainstem, hypothalamus, thalamus, and basal forebrain. This organization encompasses complex neuroanatomic, neurophysiologic, and neurochemical mechanisms that are subject to disruption from within, or as a result of incidental alterations of appropriate brain centers. The first section of this article reviews the wake-sleep disturbances that occur with lesions in defined neuroanatomic structures involved in sleep mechanisms, such as the brainstem, hypothalamus, thalamus, and cerebral hemispheres. The second section gives an overview of specific sleep alterations associated with neurologic disorders. These include stroke, Parkinson's disease, degenerative systemic disorders, multiple sclerosis, myotonic dystrophy, myasthenia gravis, brain tumors, head trauma, coma, epilepsy, and headache syndromes. PMID- 1630636 TI - The thalamus and insomnia. AB - The thalamus has been shown to play a primary role in the organization of the wake-sleep rhythm. This was confirmed by experimental findings in which athalamic cats displayed severe and persistent insomnia, and by clinical observations that thalamic degeneration, with selective or prevalent involvement of the anterior or dorsomedial nuclei, virtually abolishes the ability to generate electroencephalographic sleep patterns. Loss of sleep has been associated with autonomic (tachycardia, hyperthermia, tachypnea) and endocrine (increased plasma cortisol and catecholamine levels) activation. The clinical and experimental evidence suggests that degeneration of the anterior and dorsomedial thalamic nuclei (so-called "visceral thalamus") leads to permanent loss of autonomic and endocrine homeostasis and restorative body processes by relieving the hypothalamus of cortical inhibitory control. PMID- 1630637 TI - Narcolepsy. AB - Narcolepsy is a chronic neurologic disorder characterized by excessive daytime sleepiness, cataplexy, and premature onset of rapid eye movement sleep. It can be differentiated from other disorders causing daytime drowsiness by its clinical symptoms and by sleep laboratory studies. The disorder usually begins in adolescence and remains present throughout life. Genetic susceptibility to narcolepsy is closely associated with specific HLAs that indicate the existence of a gene in the region of the major histocompatibility complex on chromosome 6 that increases susceptibility to narcolepsy. Neurochemical studies of human and canine narcolepsy have demonstrated disturbed monoaminergic and cholinergic function that may account for impaired regulation of rapid eye movement sleep, but the link between these abnormalities and the genetic factors is still unknown. Treatment of sleepiness with stimulants and cataplexy with tricyclic antidepressants leads to substantial improvement but does not fully resolve symptoms in most patients. PMID- 1630638 TI - Dissociated states of wakefulness and sleep. AB - Both sleep clinicians and basic science researchers have been witness to a wide variety of unusual clinical and experimental phenomena that represent admixtures, incomplete declaration, or rapid oscillations of the three states of being: wakefulness, rapid eye movement (REM) sleep, and nonrapid eye movement sleep. The concept of state dissociation provides an explanation for a wide variety of bizarre clinical phenomena, including the symptoms of narcolepsy, REM sleep behavior disorder, disorders of arousal (such as sleep terrors, sleepwalking, and sleep drunkenness), automatic behavior, and some "out-of-body" experiences. The purpose of this review is to provide an overview and perspective of such conditions, encourage systematic and detailed study of these "experiments in nature," and underscore the interdependence of clinicians and researchers. PMID- 1630640 TI - The neurology of sleep. Introduction. PMID- 1630639 TI - Sleep-related obstructive and nonobstructive apneas and neurologic disorders. AB - Daytime breathing problems caused by neurologic lesions always worsen during sleep, and in certain cases abnormal breathing patterns are only seen during sleep or specific sleep states. The first clinical manifestation of maltase deficiency, myopathy, or myotonic dystrophy is often a sleep-related complaint, such as unexplained waking from sleep (insomnia) or daytime somnolence. Thus, systematic investigation during sleep of disorders impairing the loop involved in breathing is strongly encouraged. Lesions may involve sensory receptors, sensory pathways, brainstem-controlling neurons, upper motor neurons, descending motor pathways, lower motor neurons, motor nerves, neuromuscular junctions, or respiratory muscles. Most of these lesions lead to a decrease in or absence of inspiratory efforts (diaphragmatic apnea or hypopnea) during sleep. These events differ from the classic obstructive sleep apnea syndrome and the recently described upper airway resistance syndrome, which usually involve mild or significant anatomic abnormalities of the upper airway and craniofacial region. The treatment of abnormal breathing during sleep has been improved by the development of nasal ventilation methods: continuous positive airway pressure, intermittent positive pressure, and volume ventilation. These therapeutic approaches can prevent tracheostomy and diaphragmatic pacing and are more efficacious than drug treatments. Long-term compliance is generally much better in breathing disorders secondary to neurologic impairments than in cases of mild to moderate obstructive sleep apnea. PMID- 1630641 TI - Nocturnal paroxysmal dystonia and nocturnal wandering. AB - Nocturnal paroxysmal dystonia (NPD) and episodic nocturnal wanderings (ENWs) are complex motor attacks arising abruptly during sleep, especially nonrapid eye movement sleep. NPD is characterized by sudden arousal followed by motor agitation with dystonic posturing, and semipurposeful activity recurring several times per night. When short-lasting, NPD may respond favorably to carbamazepine. ENWs are unusual episodes of ambulation, with unintelligible speech, screaming, and complex, often violent, behavior that responds to anticonvulsants. In both short-lasting NPD and ENWs, electroencephalography may show some evidence of epilepsy; NPD is clinically similar to the frontal lobe seizures that arise mesially or in depth. Paroxysmal arousals (PAs) are even shorter episodes of arousal or awakening during nonrapid eye movement sleep, associated with transient dystonic posturing and related to the short-lasting NPD. PAs, short lasting NPD, and ENWs probably represent a spectrum of peculiar sleep-related epileptic seizures. PMID- 1630642 TI - Periodic, aperiodic, and rhythmic motor disorders of sleep. AB - A variety of spontaneous movements can occur during sleep. Most are unassociated with identifiable CNS pathology and are presumed to be caused by sleep-related modulation of CNS motor control systems. Individual dyskinesias occurring during sleep can be characterized not only by their frequency, rhythmicity, and anatomic predilections, but also by the stage of sleep in which they characteristically occur. Wake-pattern movement disorders improve during sleep but, contrary to common belief, they do not entirely disappear. Instead, these disorders reemerge in attenuated form, often during nonrapid eye movement sleep. The identification and proper characterization of the various sleep-related dyskinesias are greatly aided by careful polysomnographic study. PMID- 1630643 TI - Snoring, sleep apnea syndrome, and stroke. AB - Increasing evidence suggests that snoring and sleep apnea are associated with cerebrovascular diseases. Several other factors may be involved in this association because many established or potential risk factors for stroke are related to snoring and sleep apnea. These include arterial hypertension, coronary heart disease, age, obesity, smoking, and alcohol consumption. Recent epidemiologic and clinical studies indicate, however, that snoring can increase the risk of stroke independently of these confounding factors. Accumulating epidemiologic evidence of long-term harmful effects of the obstructive sleep apnea syndrome appears to be related to increasing vascular morbidity and mortality. Potential mediators among snoring, obstructive sleep apneas, and stroke include cardiac arrhythmias and other hemodynamic disturbances, increased levels of catecholamines, and disturbances in cerebral blood flow caused by sleep apneas, as well as hypoxemic periods that may potentiate atherosclerosis. PMID- 1630644 TI - Sleep in Alzheimer's disease and the sundown syndrome. AB - Approximately 10% of the elderly population have a dementing illness that manifests itself clinically by significant cognitive deficits. Half of these individuals have Alzheimer's disease (AD), a progressive degeneration of cortical and subcortical neurons. Disturbances of sleep and the sleep-wake rhythm are a common clinical observation in AD, as is "sundowning," the onset or exacerbation of delirium during the evening or night. Here we describe the neurologic basis for the disturbed sleep of patients with AD, the phenomenology of that disturbance, and its implications. Further, we describe the prevalence, possible causes, and treatment of sundowning. PMID- 1630645 TI - Basic mechanisms of sleep generation. AB - Most brainstem, thalamic, and cortical cellular types undergo similar processes during rapid eye movement (REM) sleep and wakefulness, and both these brain activated behavioral states are opposed to the resting EEG-synchronized sleep. Experimental evidence shows that during drowsiness, disfacilitation in thalamic and cortical neurons (by partial removal of influences from mesopontine, posterior hypothalamic, and basal forebrain activating systems) may coexist with active hypnogenic mechanisms. The idea of an active induction of sleep, however, still lacks firm support at the cellular level. The generation of REM sleep signs is probably caused, at least partially, by the disinhibition of mesopontine cholinergic cells, the executive elements of tonic and phasic events during dreaming sleep, following cessation of firing of inhibitory serotonergic dorsal raphe neurons. PMID- 1630646 TI - Outcomes and costs of inpatient AIDS care. PMID- 1630647 TI - Methodological issues in the study of surgical infections in war wounds. PMID- 1630648 TI - Nondeployability. PMID- 1630649 TI - Ambulatory health care needs of women deployed with a heavy armor division during the Persian Gulf War. AB - A study was undertaken to assess the health care needs of women in a combat deployment. During a 6-month period during the Persian Gulf War, 10,165 ambulatory visits from an armor division were studied. The results demonstrate that the health care needs of women can be managed by competently and broadly trained practitioners. Referral sites should provide for gynecologic consultants along with equipment and resources needed to manage pregnancy complications, pelvic pain, and abnormal cervical cytology. It is unlikely that women deployed in this setting pose a significant health care burden attributable solely to their gynecologic needs. PMID- 1630650 TI - An analysis of gynecological problems presenting to an evacuation hospital during Operation Desert Storm. AB - Very little data are available to commanders regarding gynecological problems encountered by a large female population in a combat zone for extended periods of time. The 312th Evacuation Hospital supported Operation Desert Storm, treating over 12,000 patients. Of these, 577 were treated by the gynecological service. Only six patients with nonobstetrical conditions required evacuation out of theater; the remainder returned to duty. Five of these had pre-existing conditions. There were 49 cases of pregnancy. Excluding pregnancy, the gynecological problems observed were predictable, manageable in theater, and resulted in minimal loss of manpower. PMID- 1630651 TI - Psychiatric evaluation of self-referred and non-self-referred active duty military members. AB - This study examined 300 cases of active duty Air Force members seen in an Air Force medical center outpatient mental health clinic over a 1-year period. Comparisons were made between self-referred and non-self-referred (commander directed) patients across several areas, including chief complaints/referral reasons, diagnoses, personality features, dispositions, and numbers of therapy sessions. Results showed significantly different distributions of types of chief complaints, dispositions, and treatment sessions between the two groups, and provided relative proportions of personality types distributed within each group. The dual roles of the military mental health practitioner, as provider for both the organization and the patient, are discussed. PMID- 1630652 TI - Anesthesia in military conflicts: towards simpler, safer, and higher standards. AB - The increasing military activity in the Persian Gulf necessitates that anesthesiologists in the United States should gain familiarity with the use of a draw-over vaporizer attached to a non-rebreathing circuit. Unfortunately, distributors of draw-over vaporizers in the United States do not allow anesthetists to use this equipment on humans in North America when conventional anesthesia equipment is available. Since the standard of anesthesia care in the U.S. is high, the use of a draw-over vaporizer is not allowed in most settings. Hence, this article reviews the function, the advantages, and disadvantages of a draw-over vaporizer attached to a non-rebreathing circuit. The use of an oxygen concentrator is also discussed, which increases the safety of this anesthetic delivery system. PMID- 1630653 TI - Development of the laws of war as they pertain to medical units and their personnel. AB - International law provides certain protections for medical units and their personnel during times of war. This was not always the case, but protections were gradually added and finally codified in the Geneva Conventions. The development of these protections is traced from early recorded history to modern times, and the limitations and obligations placed on medical units and medical personnel by international law are examined. PMID- 1630654 TI - Disease prevention strategies for Army aviators: clues from a descriptive analysis of the flying duty medical examination. AB - The U.S. government spends approximately $300,000 to train an Army aviator. Maintaining a healthy aviator population is important not only to the completion of the aviation mission, but also for budgetary reasons. We reviewed Army aviator physical examinations and self-reported risk behavior questionnaires from the Aeromedical Epidemiological Data Repository at Fort Rucker, Alabama, to assess aviator health. Overall, aviators are healthy adults; however, the health status of aviators can be improved by reducing tobacco use, limiting cholesterol and fat intake, and wearing hearing protection devices both during and off duty. PMID- 1630655 TI - Ambulance use in a military population: epidemiology and implications. AB - Because no studies have been reported on ambulance use in military populations, a 2-year epidemiologic study of all ambulance responses on Hickam Air Force Base was conducted. Findings included a higher utilization rate and a greater proportion of pediatric patients than might be expected in comparable civilian populations. Serious trauma was uncommon, but a wide spectrum of serious medical emergencies was seen. Advanced life support was indicated in 22% of all responses, and its availability improved patient outcome. Based on these and other findings, recommendations are made for upgrading military prehospital care to meet both base population needs and current civilian community standards. PMID- 1630656 TI - Previous hearing loss and susceptibility to future permanent threshold shifts. AB - The association between prior hearing losses and susceptibility to future permanent threshold shifts was examined by a matched pairs case-control study. Data were obtained from the United States Air Force Hearing Conservation Data Registry, which contains over three million audiometric records. Cases with permanent hearing losses were matched with normal controls for relative noise exposure intensity, years of exposure, and age. Based on analysis with normal or abnormal baseline hearing as the risk factor, cases with abnormal initial hearing were no more likely than controls to develop future permanent threshold shifts (odds ratio = 1.06, 95% confidence interval 0.61-1.85). PMID- 1630657 TI - Chronic pyridostigmine bromide administration: side effects among soldiers working in a desert environment. AB - The side effects of chronic pyridostigmine bromide administration were studied in seven male soldiers performing moderate-intensity exercise in a desert environment. A 2-week, double-blind, placebo-controlled crossover design was employed in which pyridostigmine was administered for 7 consecutive days (30 mg orally, t.i.d.). Four hours each day were spent in the heat (42 degrees C, 20% relative humidity); 2 hours rest followed by 2 hours moderate exercise (40% maximal aerobic power). Each day, subjects completed four symptom questionnaires and received three focused physical examinations. Symptoms reported did not differ between treatment groups except for fewer headaches during pyridostigmine treatment. Soldiers were unable to distinguish the effects of pyridostigmine from placebo. Pyridostigmine was associated with lower resting diastolic blood pressure (approximately 4 mmHg, p less than 0.05), smaller pupil diameter (approximately 0.5 mm, p less than 0.01), decreased handgrip strength (approximately 3%, p less than 0.05), and higher final rectal temperature (approximately 0.1 degree C, p less than 0.01). Effects of this magnitude are not likely to appreciably limit performance. We conclude that chronic pyridostigmine administration does not negatively impact on soldiers' ability to perform physical work over repeated days in a desert environment. PMID- 1630658 TI - A technique for subcutaneous knot inversion following running subcuticular closures. AB - Standard methods of running subcuticular closures frequently leave the completion knot close to the epidermis, resulting in stitch abcesses and suture extrusion. A simple technique for the subcutaneous placement of completion knots following subcuticular sutures, resulting in fewer stitch abcesses, is described. PMID- 1630659 TI - Efficacy of antiperspirants on feet. AB - Nineteen male soldiers participated in a study of the effectiveness of two antiperspirants (aluminum chlorohydrate and aluminum zirconium tetrachlorohydrex glycine) in reducing foot-sweat accumulation and injuries. Each subject was tested before and after antiperspirant application, with a 1-hour treadmill march at 5.6 km/hour in a warm environment. Both antiperspirants decreased (p less than 0.05) foot-sweat accumulation over 50%. There was also a tendency, although not statistically significant, for subjects to incur fewer blisters with antiperspirant use. However, the antiperspirants also increased (p less than 0.05) the incidence of irritant dermatitis. Nevertheless, these data suggest that the application of antiperspirants to the feet has merit in reducing serious foot injuries (blisters, trench foot) exacerbated by wet feet. PMID- 1630660 TI - Defining quality in health care. AB - The difficulty and importance of developing and implementing a definition of quality in health care is discussed. Some current definitions are considered, and a recommended definition of quality health care is presented. PMID- 1630661 TI - Decentralized operating room pharmacy services in a military teaching hospital. AB - The development, initiation, and evaluation of a decentralized pharmacy satellite within the operating room, requiring neither additional capital funding nor any major construction, is described. The satellite offers numerous programs to aid the operating room staff. Included in this effort is the complete management of all controlled substances within the operating room, post-anesthesia-care unit, and same-day-surgery unit. Pharmacists function as pharmaceutical resources playing a major role in the pain service unit. Success of the satellite is assessed via a number of parameters including staff survey response, quality assurance impact, and inventory management. PMID- 1630662 TI - High tech home care: a look at a success story. AB - The expansion of technology has allowed patients to receive intravenous therapy at home. This case study discusses the problems of a patient with diabetes mellitus and malignant otitis externa. This patient received intravenous therapy for the last 3 years of his life. In spite of several hospitalizations, he was able to return and remain home until his death. Management of the patient's discharge and home care seemed to be a major factor in his ability to remain in the community. PMID- 1630663 TI - An atypical case of brucellosis in a Turkish national. AB - Brucellosis is an endemic disease in many of the countries in which military personnel are stationed, including the Middle East, where thousands are deployed. The signs and symptoms of brucellosis are often nonspecific and diagnosis requires a high index of suspicion. This case report involves a Turkish national with an unusual febrile illness, subsequently diagnosed as brucellosis. The presentation, diagnosis, and treatment are discussed. The special relevance to the military physician is emphasized. PMID- 1630664 TI - Ambulance use in a military population: epidemiology and implications, by LTC Fred Leonard, USAF MC. PMID- 1630665 TI - [Diabetic cardiomyopathy: possible pathogenetic role of coronary microcirculation]. AB - The hypothesis that diabetes mellitus provokes a specific cardiomyopathy is supported by numerous clinical, epidemiological and anatomopathological studies. However, the frequent association of diabetes mellitus with other conditions, such as hypertension and coronary atherosclerosis, both capable of causing the dysfunction of the cardiac muscle, makes it difficult to interpret many of the data reported in the literature and contributes to the continuing debate regarding the effective existence of diabetic cardiomyopathy and its possible pathogenetic mechanisms. In clinical terms, diabetic cardiomyopathy is manifested both as an altered diastolic and/or systolic phase, assessed using various non invasive techniques, or as congested cardiac decompensation. The pathogenesis of diabetic cardiomyopathy is still not altogether clear. The alteration of the smallest coronary vessels might be responsible for the increased interstitial fibrosis found in the heart of diabetic patients. In this paper numerous data from the literature on this argument are reported and the authors advance the hypothesis that endothelial dysfunction may play a pathogenetic role in the development of cardiopathy. PMID- 1630667 TI - [4'-epidoxorubicin: its cardiotoxicity. Possible cardiac protection with gallopamil, a drug with calcium-antagonist action]. AB - The 4'-EPI-doxorubicin (4'-EDX) has shown antitumoral activity against a broad spectrum of human tumors. The same clinical reports have shown therapeutic activity comparable to doxorubicin (adriamycin), but a lower cardiac toxicity. 4' EDX cardiotoxicity appears after highest cumulative doses: 935 mg/m2 bs for 4' EDX vs 550 mg/m2 bs for adriamycin. Moreover we have observed a protective action of the calcium antagonist gallopamil. We have found an improvement in ventricular performance after using gallopamil, and a reduction of 4'-EDX cardiotoxicity. Cardiac function was evaluated by EKS, STI, echography, myocardial scintigraphy course. Our result indicates the possibility of treating tumors without serious cardiotoxic by 4'-EDX and gallopamil. PMID- 1630666 TI - [Progression of lesions of the arterial wall evaluated by ultrasonic biopsy in asymptomatic subjects and in diabetic and hyperlipidemic patients treated with bezafibrate. A 4-year follow-up]. AB - Non-invasive arterial ultrasonic biopsy (UB) has been used to evaluate and follow up arterial wall changes in four years in asymptomatic subjects, hyperlipidemics and diabetics. Both groups of patients were randomised in a treatment group (bezafibrate 400 mg daily) and in a control group. The rate of progression (ROP) into the next higher UB class was recorded by UB scans repeated every six months. In diabetics and hyperlipidemics the rate of progression (ROP, namely the percent of patients progressing to the next class) was significantly higher than the ROP in the asymptomatic subjects. However in the bezafibrate group the ROP was significantly lower than that observed in the controls. As each UB class corresponds to different levels of risks of occult coronary ischemia and cardiovascular events in the following four years, the reduction of ROP with bezafibrate was an important and positive achievement. PMID- 1630668 TI - [Heart rhythm changes in patients with chronic obstructive bronchopneumopathies: effects of different methylxanthine drugs]. AB - The present study was designed to assess effectiveness and safety and the proarrhythmic effects of two methylxanthine derivatives, doxofylline and aminophylline, in the management of chronic obstructive pulmonary disease associated with cardiac rhythm disturbances. Fourteen patients of both sexes (9 male, 5 female) with a mean age of 54 (range 43 to 66 years) with concomitant chronic obstructive pulmonary disease and high incidence of ventricular (VPB) and/or supraventricular (SVPB) premature beats were selected. The study was performed in a double-blind randomized cross-over trial. Following a proper wash out period, in each phase patients were administered intravenously 400 mg b.i.d. of doxofylline or 480 mg of aminophylline b.i.d. (rate of infusion: 60 min) according to the cross-over design. A 24-hour Holter monitoring was carried out before the onset of the treatments and at the end of each venous infusion of methylxanthines. Spirometry for measurement of forced expiratory volume in one second and clinical parameters were also evaluated. Parametric variables were evaluated by analysis of variance. Kruskal-Wallis test was used to estimate non parametric variables. A p value less than 0.05 was considered statistically significant. We observed a significant reduction in the occurrence of VPB/24 h (p less than 0.05 vs basal value) and in the total number of beats (p less than 0.01 vs basal value and p less than 0.05 vs aminophylline) after doxofylline administration, whereas no changes from baseline in the incidence of premature beats and in the mean 24-hour heart rate were reported after aminophylline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630669 TI - [Effects of fibrinolytic therapy in acute ischemia of the lower limbs]. AB - In this paper the Authors illustrate their experience of loco-regional fibrinolytic medical treatment in patients suffering from acute thrombotic-type ischemia of the lower limbs. The clinical, ultrasonographic and angiographic criteria leading to the choice of this form of treatment rather than surgery are examined. The Authors outline the reasons which led them to give preference to the use of plasminogen tissue activators (rt-PA) rather than other fibrinolytic agents; the results obtained are evaluated not only in terms of immediate permeability but also in relation to the additional procedures required to ensure a correct therapeutic iter. In conclusion, the paper underlines the need to assess the indications for this type of therapy with great care since "washing" the distal vascular bed may be decisive for successful treatment even in the event of possible future surgery. PMID- 1630670 TI - [Aortic coarctation and intracranial aneurysm: an unusual association. Description of an unusual case and diagnostic-therapeutic considerations]. AB - A case of double unruptured intracranial aneurysm associated with aortic coarctation is presented. The main characteristics of the unusual association, the diagnostic criteria and the surgical strategies are reviewed. PMID- 1630671 TI - [Prognostic significance of thallium-201 scintigraphy in patients with previous myocardial infarct]. AB - With the purpose of ascertaining the predictive value of residual myocardial ischemia, in stable clinical conditions at a distance after myocardial infarction, on the incidence of late cardiac events, we evaluated 55 patients 24.2 +/- 11.4 months after myocardial infarction with thallium-201 stress test imaging. All patients were either asymptomatic or with stable effort angina pectoris, well controlled with medical treatment. In the next follow-up period, whose duration has been 22.4 +/- 14.4 months, the incidence of unfavourable cardiac events, like unstable angina, reinfarction, coronary bypass surgery, sudden cardiac death has been monitored. Thirty-one patients (56.4%) presented a reversible perfusion defect (RPD) in one or more myocardial segments; 17 of these 31 showed cardiac events during follow-up. Only 2 patients of the remaining 24 without RPD had cardiac events, with a significant difference (p less than 0.01). The patients with RPD only in peri-infarct areas had a relatively smaller number of cardiac events, with respect to those patients with RPD also or only in distant areas. Fifteen of 21 patients with RPD in 2 or more segments manifested cardiac events, compared to 2 of 10 patients with RPD in only one segment (p less than 0.01). In 10/55 patients, increased lung uptake of thallium-201 activity was observed; 8 of them presented cardiac events (p less than 0.01). This analysis confirms the high predicting value of thallium-201 RPD imaging on the incidence of cardiac events in patients controlled at a distance after myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630672 TI - [AIDS in Italy: an update to 31 December 1991]. PMID- 1630673 TI - [AIDS in the world, as of 1 October 1991]. PMID- 1630674 TI - [Cardiac involvement in pheochromocytoma. A report of 6 cases]. AB - Pheochromocytoma is a rare case of sustained hypertension or hypertensive crisis: sometimes it may occur with several aspecific symptoms or hypotension. The literature reports frequent myocardial involvement in patients affected by pheochromocytoma. Adrenergic hormone effects are responsible for a functional coronary insufficiency which causes myocardial damage. The cardiac involvement may appear with symptoms of different severity that sometimes represent the only symptoms of the neoplasia. Clinical and instrumental cardiac alterations observed in 6 patients suffering from pheochromocytoma are reported. Electrocardiographic abnormalities were found in 5 out of 6 patients. Inferior myocardial infarct was present in one case; in two patients electrocardiogram showed left ventricular hypertrophy and negative T wave; frequent ventricular extrasystoles in one case and complete atrio-ventricular block in another were found during the hypertensive crisis; in one patient the electrocardiogram showed STT changes and in the last one, left ventricular hypertrophy, more evident in the interventricular septum, was present at the echocardiogram. All subjects underwent surgical treatment after a period of drug therapy. To date surgery is the only possibility to eliminate myocardial malignant effects of catecholamines. PMID- 1630675 TI - [A clinical case: coronary vasospasm induced by exercise after stopping nifedipine therapy]. AB - A 60-year-old man with atypical chest pain not submitted to adequate diagnostic procedures was treated on an empirical basis with nifedipine 20 mg b.i.d. The patient was referred to our institution where a first symptom-limited exercise stress-test during treatment was performed; neither S-T alterations nor clinical symptoms were induced at the maximal tolerated work load. Therefore we suggested a short period of hospital stay to repeat the stress-test after a progressive tapering off of the drug with the aim of obtaining a more definite diagnosis. However the patient refused and an at-home nifedipine withdrawal was planned. Some days later a second test showed marked S-T segment elevation in leads V4 to V6; concomitant high-grade ventricular arrhythmias and anginal pain occurred. Both the ECG alterations and the clinical symptom promptly regressed interrupting the test and administering sublingual isosorbide dinitrate. A coronary angiography performed few days later showed only a single and no significant stenosis of the left anterior descending artery (60%). The clinical and electrocardiographic pictures were therefore attributed to stress-induced vasospastic ischemia. A week later a third maximal stress-test during further treatment with nifedipine was totally negative. The pathophysiological mechanisms of rest and stress-induced vasospastic angina and the usefulness of Ca-blocking agents are discussed. PMID- 1630676 TI - [Metabolic changes in the patient with essential hypertension]. AB - The aim of the present study was to evaluate a number of parameters in a group of patients with essential hypertension and then compare the results with those in a group of healthy normotensive subjects. One hundred and fifty-six patients with essential hypertension (EH) in the non-complicated form (73 males, 83) females; mean age: 54.8 +/- 0.9 years) were selected and compared with 150 normotensive subjects matched for age and sex. After a 2-week period of wash-out during which patients followed a diet with normal sodium and calorie content, body mass index, systolic and diastolic arterial pressure (AP), mean arterial pressure (MAP), heart rate in clino- and orthostatism were measured and blood was collected to assay glycemia, total cholesterolemia, LDL and HDL cholesterolemia and triglycerides. In the group of patients suffering from EH all the above parameters were found to be significantly higher than in normotensive control subjects. In particular, in the hypertensive population the prevalence of obesity was 21.3%, hyperglycemia 26.9%, hypercholesterolemia 65.1% and smoking 36.4%. When the possible relation between one or more risk factors and AP values was assessed, it was found that in hypertensive patients the presence of hyperglycemia alone or in association with other metabolic disorders led to the highest MAP findings. Moreover, having studied the correlation rate of the various parameters, it was seen that in both the hypertensive and normotensive populations systolic AP measured in clinostatism positively correlated with glycemia, total cholesterolemia, and age, whereas correlations were not found between clinostatic diastolic AP and the above parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630677 TI - [The frequency of early coronary reperfusion assessed by electrocardiographic criteria in relation to the timing of thrombolytic therapy in acute myocardial infarct]. AB - This study was aimed at assessing coronary reperfusion in patients with acute myocardial infarction (AMI) undergoing systemic thrombolysis with SK and rtPA. The occurrence of reperfusion was related to the time of treatment. The evaluation of reperfusion was performed by monitoring ST segment changes. 56 patients with AMI were studied. 22 out of these (39.2%) showed a significant decrease (greater than 50%) in ST segment sum (sigma ST) at 100 minutes from the beginning of the treatment. Analysis of the relationship between reperfusion and elapsed time between the onset of symptoms and the treatment, reveals that the reperfusion is less frequent (p less than 0.05) in patients treated at 180 minutes or later. The standard electrocardiogram appears as the most useful method to evaluate indirectly coronary reperfusion in acute myocardial infarction. A further refinement of this method is desirable to recommend its widespread clinical use. The assessment of reperfusion by means of ECG in large series of patients will permit the evaluation of the benefits of reperfusion, in terms of survival, complications and incidence of ventricular dysfunction. PMID- 1630678 TI - [Observations on the natural history of heart failure. Changes due to the therapeutic use of captopril]. AB - The purpose of this research was a retrospective evaluation of the mortality rate in 138 patients, considered after the first hospitalisation due to heart failure. After 5 years, the mortality rate was higher in the 54 patients with dilatative cardiomyopathy (74.3%), compared to the 44 patients with coronary heart disease (54.5%), while the 40 patients with valvular heart disease showed a lower mortality (37.5%). The mortality rate was higher in patients admitted in higher NYHA class. The primary aim of this research was to assess the effects of captopril on mortality in 101 treated patients, compared to 37 non treated patients, both receiving conventional treatment for heart failure. Between the 2 groups, the mortality rate showed lower percentage values for patients treated with captopril, with significant difference (p less than 0.01) at controls carried out every 12 months, until 5 years. Progressive heart failure was the greater cause of death in both groups, while the deaths classified as due to arrhythmia without pump failure were less frequent. Deaths due to reinfarction in patients with coronary heart disease showed lesser percentage values in patients treated with captopril. This research demonstrated the high mortality rate affecting a group of patients after the first hospitalisation due to heart failure. The addition of captopril to conventional treatment for heart failure significantly reduced mortality. PMID- 1630679 TI - [The structural aspects of the pharmacological activity of calcium antagonists. A general profile and the results of a pilot study of nicardipine]. AB - The authors examine the most recent findings on arterial hypertension with particular emphasis to morphological changes of the arterial wall and to the results of nicardipine treatment in spontaneous hypertensive rats (SHR). According to these assumptions the authors evaluate the effects of nicardipine on the microvascular network by means of a funduscopic examination in 8 hypertensive patients. The preliminary data suggest that nicardipine has a positive structural and morphological effect on the vessel network. PMID- 1630680 TI - [The Study Group of Quinapril in Arterial Hypertension. The Steering Committee]. AB - The efficacy and safety of the treatment of arterial hypertension with the ACE inhibitor quinapril, were evaluated in a multicentre study conducted in Italy. The study, lasting 14 weeks, after a preliminary wash-out period, allowed response-based titration of quinapril dose from 10 mg to 40 mg once a day, with provision to combine additional hydrochlorothiazide (12.5 to 25 mg), in case of persistently high diastolic pressure levels. The efficacy sample included 1267 patients: at therapy week 14, 78.6% of patients were treated with quinapril alone. Global response rate (intent-to-treat) was 83.3%, with a mean reduction of diastolic pressure of 15.8 mmHg (95% confidence interval from 15.5 to 16.2 mmHg). 91 patients reported 126 associated adverse events (7.0%); the most frequently reported event was cough (2.7%). First-dose hypotension was rarely reported (1.3%), even in elderly and diabetic patients. PMID- 1630681 TI - [The effect of gallopamil on myocardial perfusion in angina of effort]. AB - To value stress tolerance and stress myocardial perfusion before and after a week of oral therapy with gallopamil 150 mg daily, we studied 10 patients suffering from stable effort angina. We performed bicycle exercise stress testing and thallium scintigraphy (Tl) with planar technique in 3 projections (anterior posterior and oblique left anterior at 45 and 70 degrees) according to the current standards. We valued systolic and diastolic blood pressure (SBP-DBP), heart rate (HR) and HR-SBP product at rest, at symptoms stress-induced and at the end of the procedure. Moreover we valued work threshold of chest discomfort and ischemia, the maximal work capacity and the perfusion defects according to a Tl score obtained dividing the 3 projections in 5 segments and fixing a value according to the observed perfusion from 0 = normal perfusion to 3 absent perfusion. We observed a significant reduction of basal HR (77 vs 71, p = 0.05), SBP (147 +/- 15 vs 131 +/- 15 mmHg, p = 0.001), DBP (91 +/- 6 vs 83 +/- 6 mmHg, p = 0.002). Work threshold of chest discomfort and ischemia significantly arose (8 +/- 3 vs 11 +/- 4 min., p = 0.002; 6 +/- 3 vs 10 +/- 4 min., p = 0.001). The HR SBP product at the maximal work capacity and the Tl score significant decreased (31650 +/- 6239 vs 29406 +/- 5418, p = 0.003; 8 +/- 2 vs 5 +/- 1, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630682 TI - [Rokitamycin. The new macrolide]. PMID- 1630683 TI - ["Multiorgan failure" in surgery: its physiopathology, prevention and treatment. A review of the literature]. AB - At present multiorgan failure (MOF) is the complication with the highest mortality after emergency or elective general surgery. The syndrome seems to find its pathogenesis out of the very complex interactions of endogenous and exogenous mediators; instead the physiopathology seems to depend on cellular oxygen deficiency. The authors refer the common criteria defining organ and/or system damage during MOF and analyse the available possibilities for their treatment. In this regard they stress the role of prevention, which relies on the opportune treatment of earlier stage of shock, constantly preceding the syndrome, and on the intensive organ/systems functions monitoring to obtain an early and rational correction of the alterations taken away. PMID- 1630684 TI - [Hurthle-cell tumors of the thyroid]. AB - In the last 10 years 20 patients with Hurthle tumors were observed at Institute of Surgery and Oncology of Cagliari University. 17 were females and 3 males with a median age of 42 years. Tumors were malignant in 7 cases and benign in 13. A total thyroidectomy was performed in all patients with carcinoma and in 2 with adenoma because of concurrent goiter. The remaining patients were treated with a less extensive surgery. Two patients with carcinoma had a cervical node metastases at 12 and 67 months, treated by surgery (followed by radioiodine therapy in one). All patients are alive and disease free at 72 months of median follow-up. None of patients with benign adenomas recurred at 47 months of median follow-up. A longer-term follow-up is necessary in order to evaluate the benignity of adenomas. PMID- 1630685 TI - [Intestinal obstruction in colorectal neoplasms. Our experience with 50 cases]. AB - From January 1985 to December 1989 in our Department 178 patients were operated for colorectal carcinomas. Fifty (28%) underwent emergency procedure for intestinal obstruction. The male-female ratio is about 1. The mean age is 79.6 (range 40-91), but 76% of patients is 60-85 years old. The rectum-sigmoid junction was the most affected (30%), followed by the rectum (18%) and the sigma (16%). Thirty-five (70%) patients underwent intestinal resection. The early postoperative death rate is 18% (9 cases). All the patients operated upon had Dukes stage B-C neoplasms. PMID- 1630686 TI - [The diagnosis and treatment of renal oncocytoma. Our experience]. AB - Personal experience of the treatment of renal oncocytoma is compared with reported data. Furthermore the problems relating to the diagnosis and treatment of this tumour, characterised, in many cases, by its lack of symptoms and tricky histopathological classification, are examined in greater depth. PMID- 1630687 TI - [Perioperative treatment with thymostimulin in patients with stomach and colorectal neoplasms. Our experience with 114 cases]. AB - The authors report their experience about the use of the timostimoline in the perioperative time in 114 cases of gastric and rectum cancer. They think that this method can be of help for neoplastic patients about the time of surgical stress. PMID- 1630689 TI - [A rare case of massive digestive hemorrhage. Carcinoid of the small intestine]. AB - The authors reports a case of massive digestive hemorrhage produce by a carcinoid of the small intestine. Having reviewed the most frequent causes of primary hemorrhage of the mesenteric small intestine, attention is focused on the difficulties o making an etiological and topographical diagnosis, in spite of using the most advanced instrumental research methods. The paper concludes that explorative laparotomy is the sole method for making a precise diagnosis and performing appropriate surgical treatment. PMID- 1630688 TI - [Leiomyoma of the stomach. A report of a case with exogastric development]. AB - The authors report a case of a large, exogastric, pedunculated leiomyoma of the stomach. Following a review of the literature, the paper describes the clinical and therapeutic aspects of these tumors and underlines the diagnostic difficulties of this relatively rare gastric pathology. PMID- 1630690 TI - [2 true cysts of the spleen. Case reports]. PMID- 1630691 TI - [An aneurysm of the extracranial carotid. A report of an interesting clinical case]. AB - One case of extracranial carotid artery aneurysm observed is reported. This uncommon and interesting vascular disorder is still under discussion even if the present tendency is to treat it actively by reconstructive surgical procedures that make it possible to avoid the natural aneurysm complications with a low risk of postoperative neurological lesions. PMID- 1630692 TI - [The use of human fibrin glue in the repair of recurrent mucosal prolapse in ileostomy]. PMID- 1630693 TI - [Peptic ulcer: 3 little-known symptoms]. PMID- 1630694 TI - [What treatment protocol for lobular carcinoma of the breast?]. PMID- 1630695 TI - [Simvastatin in the treatment of hypercholesterolemia in the aged. An epidemiological and clinical study]. AB - The paper review the literature on the subject and underlines the importance of hypercholesterolemia. It also reports the findings of the large trials, works and consensus studies, including the results of the Framingham Study, the Lipidic Research Clinics Program and the main international conferences. On the basis of these findings, it assesses the hypocholesterolemic effect of simvastatin in a sample group of 51 mainly geriatric outpatients following a standard period of preliminary dietary therapy. Subjects were treated with 20 mh/day simvastatin for not less than one month, after which lipidic parameters were evaluated and revealed significant variations: circulating cholesterin was reduced from 322 mg% +/- 49.4 to 225 mg% +/- 37.6 (p less than 0.001), the LDL-lipoprotein level fell from 229 mg% +/- 6.6 to 152 mg% +/- 36.3; HDL-lipoproteins showed no significant variation, nor did other tests to ascertain possible hepatic involvement or other parenchymas secondary to the use of simvastatin. Overall cholesterol levels decreased from 16423 mg% to 11511 mg%, equivalent to 29.9%. Lastly, simvastatin also proved to be clinical efficacious, and was easy to manage and well tolerated by elderly patients. All subjects responded equally well to treatment independent of their general condition and sex. Basal cholesterolemia in elderly subjects decreased from 320 mg% +/- 46.3 to 226 mg% +/- 33.2 (p less than 0.001) and in adults from 325 mg% +/- 56.6 to 224 mg% +/- 46.5 (p less than 0.001); LDL cholesterol decreased from 232 mg% +/- 46.5 to 153 mg% +/- 35.6 (p less than 0.001) and from 224 mg% +/- 46.6 to 147 mg% +/- 38.7 (p less than 0.001) respectively. PMID- 1630696 TI - [Effects of fenoverine on biliary kinetics evaluated by hepatobiliary scintigraphy with 99mTc-Br-IDA]. AB - Hepatobiliary scintigraphy was used to evaluate the action of fenoverine in 16 patients suffering from dyskinesia of the biliary tract; the drug was administered in doses of 300 mg per day per os for 20 days, the patients being subjected to hepatobiliary scintigraphy before and after treatment. The following parameters--accurate indicators of the motor coordination of the biliary tract- were evaluated: tracer appearance time in the gallbladder (Tc) and in the intestine (Ti). After treatment there was a normalization of these two parameters which initially were extended. Statistical analysis showed a highly significant reduction in these times. Stress is laid on the importance of hepatobiliary scintigraphy in the diagnosis of biliary dyskinesia and on the effectiveness of fenoverine in the treatment of this conditions. PMID- 1630697 TI - [Antibiotic prophylaxis with aztreonam in general surgery]. AB - Personal experience in peroperative antibiotic prophylaxis with aztreonam (Azactam) in 81 patients undergoing abdominal surgery of choice is reported. The usefulness, handiness and lack of side-effects of this parenteral drug are reiterated. The incidence of surgical wound infections was 2.5%, while that of associated infections was 6.1%. Considering these results, the use of aztreonam (Azctam) is recommended in peroperative prophylaxis as a drug of choice. PMID- 1630698 TI - [Acute renal failure caused by treatment with diuretics and ACE inhibitors in the absence of renal artery stenosis]. AB - The Authors describe a clinical case of a patient affected by arterial hypertension of severe degree (IV grade OMS) that during therapy with ACE inhibitors and diuretics developed acute renal failure that reversed after stopping treatment. The clinical course was quite similar to acute renal failure induced by ACE inhibitors and diuretics in patient with bilateral renal artery stenosis. In interpreting the pathogenesis, the Authors suppose, beside a reductions of effective plasma flow, the coexistence of hyalinosis of renal arterioles. They underline the necessity of monitoring renal function at least in the first weeks of therapy when a treatment with ACE inhibitors and diuretics is started especially in patients with hypertension of high degree and/or reduced renal function. PMID- 1630699 TI - [Partial remission of non-Hodgkin's lymphoma (stage IV-B) following immunostimulating therapy with thymopentin]. AB - Therapy of low-grade of malignancy non-Hodgkin's lymphoma in an advanced stage is still under discussion: aggressive poly-chemotherapies, such as radiotherapy and conventional chemotherapies did not prove to be more effective than conservative treatments. We report the case of a woman suffering from a low-grade of malignancy non-Hodgkin's lymphoma (stage IV-B). She was in such bad general conditions that she could not be treated with chemotherapy. She received an immunostimulating drug, thymopentin for 10 months. After this treatment, the general condition of the patient was improved and a partial remission of the lymphoproliferative disease was observed. The patient is still in constant fairly good health. PMID- 1630700 TI - [Castleman's disease. A clinical case]. AB - Castleman's disease is an uncommon lymph node syndrome. It is usually a lymphoid hamartoma, rarely systemic. We report a case of Castleman's multicentric disease observed in our hospital and review the literature. In this work we review prognosis, follow-up and therapy of 46 multicentric disease reported in the literature. PMID- 1630701 TI - [Cardiotoxicity caused by radiation. Description of 2 clinical cases]. AB - The paper reports two cases of valvular cardiac lesions and pericardial effusion caused by radiation. The widespread use of radiotherapy makes this a highly relevant problem. Radiation most frequently causes damage to the pericardium leading to pericardial effusion, and in some cases provokes myocardial, valvular and coronary lesions and even myocardial infarction. Cardiotoxicity depends on the radiation dose which must generally exceed 40 Gy. Radiated patients must be carefully monitored so as to diagnose cardiac lesions at an early stage. The ongoing improvement of radiotherapy techniques is the best means of preventing cardiac damage due to radiotherapy. PMID- 1630702 TI - [Acute renal damage caused by ampicillin. Description of a case]. AB - Approximately one week after a cycle of antibiotic therapy using ampicillin for pulmonary inflammation, an 82-year-old woman developed symptoms of acute renal insufficiency reminiscent of nephrotic syndrome. Symptoms were completely reversible and normal renal function was recovered (even after 14 months of follow-up). The Authors conclude by attributing this to acute tubulo-interstitial nephropathy due to hypersensitivity to ampicillin. PMID- 1630703 TI - [Zieve syndrome. Description of a clinical case]. PMID- 1630704 TI - [Churg-Strauss vasculitis in a 53-year-old man]. AB - The Authors describe a 53 year old patient, who, after suffering from asthma over the past 10 years, presented with abdominal pain, diarrhoea, dyspnea, petechias on lower limbs, and subsequently developed fever, polyneuritis, pericardial effusion and renal failure. Laboratory showed elevated IgE, presence of antinuclear antibodies to DNA, serum rheumatoid factor and peripheral eosinophilia. The clinical course was suggestive for systemic vasculitis; lung, skin biopsies and renal angiography confirmed this diagnosis: the association with asthma and eosinophilia fulfill the diagnosis of allergic angiitis and granulomatosis (Churg-Strauss syndrome). PMID- 1630705 TI - CHAP: America's most achievable health care reform. PMID- 1630706 TI - Gestures of dominance, gestures of defiance. PMID- 1630707 TI - Managed care, Democrats' health reform, and nursing reimbursement. PMID- 1630708 TI - AIDS--sole cause or cofactors? PMID- 1630709 TI - Deemed status for CHAP. A new standard for health care. AB - The board chair of the Community Health Accreditation Program (CHAP) reflects on the implications of federal recognition of CHAP. In challenging the status quo, CHAP has shown that a voluntary, consumer-based alternative can protect the public and promote excellence. PMID- 1630710 TI - CHAP: nursing's legacy of leadership. AB - In the story of CHAP's fight for deemed status, Mitchell, CHAP's president, finds important opportunities for nursing to exert moral leadership and initiate political reforms that will have a lasting impact on the quality of community based care. PMID- 1630711 TI - Teaching health care public policy. PMID- 1630713 TI - General nursing education. Prerequisite to midwifery. PMID- 1630712 TI - The persuasive proposal. A reviewer's perspective. PMID- 1630714 TI - "Alternative provider" ... a way of referring to nurses ... offering primary care services. PMID- 1630715 TI - Community health nurse: canary in a mine shaft? PMID- 1630716 TI - CRNA credentials overlooked. PMID- 1630717 TI - Weaning recommendations: the scientific basis. AB - Current weaning recommendations are based on nutritional need, physiologic maturation, and the behavioral and developmental aspects of infant feeding. Inadequate energy and protein intake and deficiencies of iron, zinc, vitamin A, and vitamin D are the most commonly observed nutrient deficiencies during infancy and weaning recommendations have focused on their prevention. This article reviews the data and summarizes implications for infant weaning in both developed and developing countries. Current published recommendations for infant feeding are outlined and major concerns are highlighted. PMID- 1630719 TI - Vitamin D and psoriasis. AB - Skin can serve as the source of vitamin D when exposed to sunlight so that cutaneous 7-dehydrocholesterol can be converted to the vitamin. Skin is also a target organ for the hormone form of vitamin D: 1,25-(OH)2D3. Both skin keratinocytes grown in tissue culture and samples of human skin have the nuclear receptor for 1,25(OH)2D3. New results suggest that this hormone or its analogs may be effective in treating some forms of psoriasis. PMID- 1630718 TI - Treatment of iron-deficiency anemia complicated by scurvy and folic acid deficiency. AB - We present a case of a child with iron-deficiency anemia, folic acid deficiency, and scurvy. His anemia proved refractory to treatment with iron until he received both folic acid and vitamin C supplementation. This case illustrates the importance of the evaluation of ascorbic acid and folate status in treating iron deficiency anemia initially refractory to iron supplementation, because multiple nutrient deficiencies may coexist. PMID- 1630720 TI - Acetyl-carnitine and Alzheimer's disease. PMID- 1630721 TI - Supplemental dietary potassium reduced the need for antihypertensive drug therapy. PMID- 1630722 TI - Vitamin B6 and immune function in the elderly and HIV-seropositive subjects. AB - Vitamin B6 plays an important role in immune response. A recent investigation of healthy elderly subjects in a vitamin B6 depletion-repletion study indicates that B6 deficiency impairs interleukin-2 production and lymphocyte proliferation. Another study in HIV-1-infected patients found impaired immune responsiveness in patients with compromised vitamin B6 status. PMID- 1630723 TI - Health claims on foods: American style. PMID- 1630724 TI - Health claims: omega-3 fatty acids and cardiovascular disease. PMID- 1630725 TI - The homocysteine theory of arteriosclerosis. PMID- 1630726 TI - Mechanisms of stress: a dynamic overview of hormonal and behavioral homeostasis. AB - Environmental events, both physical and emotional, can produce stress reactions to widely varying degrees. Stress can affect many aspects of physiology, and levels of stress, emotional status, and means of coping with stress can influence health and disease. The stress system consists of brain elements, of which the main components are the corticotropin-releasing hormone (CRH) and locus ceruleus (LC)-norepinephrine (NE)/autonomic systems, as well as their peripheral effectors, the pituitary-adrenal axis and the autonomic system, which function to coordinate the stress response. Activation of the stress system results in behavioral and physical changes which allow the organism to adapt. This system is closely integrated with other central nervous system elements involved in the regulation of behavior and emotion, in addition to the axes responsible for reproduction, growth and immunity. With current trends in stress research which focus on understanding the mechanisms through which the stress-response is adaptive or becomes maladaptive, there is a growing association of stress system dysfunction, characterized by hyperactivity and/or hypoactivity to various pathophysiological states. The purpose of this review is to 1) define the concepts of stress and the stress response from a historical perspective, 2) present a dynamic overview of the biobehavioral mechanisms that participate in the stress response, and 3) examine the consequences of stress on the physiologic and behavioral well-being of the organism by integrating knowledge from apparently disparate fields of science. PMID- 1630727 TI - Oxytocin and sexual behavior. AB - The neurohypophyseal hormone oxytocin has been implicated in many aspects of reproduction including sexual behavior. This review considers the hypotheses that oxytocin and/or the neural events surrounding the release of oxytocin may have behavioral effects during sexual arousal, orgasm, sexual satiety and other aspects of sociosexual interactions. PMID- 1630728 TI - Biochemical correlates for behavioral deficits induced by secalonic acid D in developing mice. AB - Humoral signals (neurotransmitters and hormones) control cell division, migration, and differentiation processes which define the organization of brain pathways. Alterations in maternal, fetal, and neonatal biochemistry during critical periods of neurogenesis may irreparably alter the circuitry and, thus, postnatal behavior of young animals. Secalonic acid D (SAD), an ergochrome mycotoxin, causes behavioral and neurochemical deficits in developing mice following prenatal (transplacental) or early postnatal (transmammary) exposure. SAD-induced functional abnormalities include delays in reflex behaviors, integrated neuromuscular activity and strength, stress adaptation responses, and sensory discrimination. These behavioral changes are associated with reductions of brain monoamine neurotransmitter levels in both fetuses and neonates. SAD also alters concentrations of maternal plasma corticosteroids and fetal cyclic nucleotides during midgestation. SAD thus modulates several chemicals in pregnant mice and their fetuses which contribute to brain development, suggesting that this mycotoxin may pose a neuroteratogenic hazard to other immature mammals, including human infants. PMID- 1630729 TI - Hormone-dependent aggression in male and female rats: experiential, hormonal, and neural foundations. AB - Hormone-dependent aggression in both male and female rats includes the distinctive behavioral characteristics of piloerection and lateral attack. In males the aggression is dependent on testicular testosterone and is commonly known as intermale aggression. In females, the aggression is most commonly observed as maternal aggression and is dependent on hormones whose identity is only beginning to emerge. The present review examines the experiential events which activate hormone-dependent aggression, the relation of the aggression to gonadal hormones, and the neural structures that participate in its modulation. In males and females, the aggression is activated by cohabitation with a conspecific of the opposite sex, by competitive experience, and by repeated exposure to unfamiliar conspecifics. In the female, the presence of pups also activates aggression. In both males and females, hormones are necessary for the full manifestation of the aggression. The essential hormone appears to be testosterone in males and a combination of testosterone and estradiol in females. The information available suggests the neural control systems for hormone dependent aggression may be similar in males and females. It is argued that hormone-dependent aggression is behaviorally and biologically homologous in male and female rats. PMID- 1630730 TI - Do essential fatty acids play a role in brain and behavioral development? AB - The membrane phospholipids of the brain contain high levels of polyunsaturated fatty acids (PUFA), particularly arachidonic acid, 20:4n-6 and docosahexaenoic acid, 22:6n-3. These long-chain PUFA are synthesized from their respective essential fatty acid (EFA) precursors, linoleic acid, 18:2n-6 and linolenic acid, 18:3n-3. Although the necessity of n-6 fatty acids for optimum growth has been established, a similar requirement for those of the n-3 family is less clear. The rapid accumulation of the long-chain n-3 PUFA in the brain during prenatal and preweaning development suggests that the provision of n-3 fatty acids to the developing brain may be necessary for normal growth and functional development. The intent of this review is to assess the experimental work which addresses this question, most of which has been conducted on rodents. The emphasis will be on studies which measure behavioral outcomes, and particular attention will be paid to methodological issues which affect the interpretation of these data. An integration of the research findings will be presented and discussed in light of possible implications for therapeutic interventions. PMID- 1630731 TI - The borderline hypertensive rat (BHR) as a model for environmentally-induced hypertension: a review and update. AB - In recent years, the burgeoning disciplines of health psychology and behavioral medicine have renewed interest in the important role that environmental factors can play in the disease process. Nowhere is this concern more well-founded than in the area of cardiovascular disorders, particularly hypertension. Epidemiologists and clinicians have long suspected that stressful life events can be a sufficient trigger for the expression of hypertension in some individuals. To understand better the ways in which these variables interact in the disease process, researchers have tried, with limited success, to produce experimental hypertension in animals by exposing them to stressful environmental paradigms. Additionally, recent investigations using the borderline hypertensive rat (BHR) have demonstrated the important role genetic factors can play in mediating both the behavioral and cardiovascular responses to environmental stressors. The current paper will review these attempts and discuss recent data from experiments using a relatively new animal model that appears to be especially appropriate for the study of environmental-genetic factors in the elaboration of essential hypertension. We will also discuss potential mechanisms by which environmental stress influences arterial pressure and suggest avenues for further inquiry into the stress-disease relationship. PMID- 1630732 TI - Genetic hypertension and increased susceptibility to cerebral ischemia. AB - A review of the sensitivity of genetically hypertensive rats to cerebral ischemia was presented together with original data describing the systematic comparison of the effects of focal ischemia (permanent and temporary with reperfusion) performed in hypertensive and normotensive rats (i.e., blood pressures verified in conscious instrumented rats). Microsurgical techniques were used to isolate and occlude the middle cerebral artery (MCAO) of spontaneously hypertensive (SHR), Sprague-Dawley (SD) and Wistar Kyoto (WKY) rats at the level of the inferior cerebral vein. Following permanent (24 h) MCAO, persistent and similar decreases in local microvascular perfusion (i.e., to 15.6 +/- 1.7% of pre-MCAO levels) were verified in the primary ischemic zone of the cortex for all strains using Laser-Doppler flowmetry. A contralateral hemiplegia that occurred following MCAO, evidenced by forelimb flexion and muscle weakness, was greater in SHR (neurological grade = 2.0 +/- 0.1) than SD (1.0 +/- 0.4) or WKY (0.7 +/- 0.4) rats (N = 7-9, p less than 0.05). SHR also exhibited sensory motor deficits following MCAO compared to sham-operation, with decreased normal placement response of the hindlimb (% normal = 20 vs. 83, N = 23-30, p decreased rota-rod (41 +/- 7 vs. 126 +/- 19 on rod, N = 10-15, p less than 0.05) and balance beam (25 +/- 5 vs. 116 +/- 29 s on beam, N = 5-7, p less than 0.05) performance. However, an index of general motor activity was not affected by permanent MCAO. Triphenyltetrazolium-stained forebrain tissue analyzed by planimetry revealed a significantly larger and more consistent cortical infarction in SHR (hemispheric infarction = 27.9 +/- 1.5%) compared to SD (15.4 +/- 4.1%) and WKY (4.0 +/- 2.4%) rats (N = 7-9, p less than 0.05), occupying predominantly the frontal and parietal areas. Also, a significant degree of ipsilateral hemispheric swelling (4.6 +/- 0.9%, N = 7-9, p less than 0.05) and increased brain water content (78.4 +/- 0.3% to 80.4 +/- 0.2%, N = 8-9, p less than 0.05) was identified in SHR that was not observed in SD or WKY rats. A novel model of temporary MCAO also was evaluated in the hypertensive and normotensive rat strains. Initially, the effect of increasing MCAO-time followed by 24 h reperfusion in SHR was studied. During temporary MCAO (20 to 300 min), persistent and stable decreases in local microvascular perfusion (i.e., to 15-20% of pre-MCAO levels) were verified in the primary ischemic zones of the cortex.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1630734 TI - Premature rupture of membranes. PMID- 1630733 TI - Metabolic fuels and reproduction in female mammals. AB - A complete reproductive cycle of ovulation, conception, pregnancy, and lactation is one of the most energetically expensive activities that a female mammal can undertake. A reproductive attempt at a time when calories are not sufficiently available can result in a reduced return on the maternal energetic investment or even in the death of the mother and her offspring. Numerous physiological and behavioral mechanisms link reproduction and energy metabolism. Reproductive attempts may be interrupted or deferred when food is scarce or when other physiological processes, such as thermoregulation or fattening, make extraordinary energetic demands. Food deprivation suppresses both ovulation and estrous behavior. The neural mechanisms controlling pulsatile release of gonadotropin-releasing hormone (GnRH) and, consequently, luteinizing hormone secretion and ovarian function appear to respond to minute-to-minute changes in the availability of metabolic fuels. It is not clear whether GnRH-secreting neurons are able to detect the availability of metabolic fuels directly or whether this information is relayed from detectors elsewhere in the brain. Although pregnancy is less affected by fuel availability, both lactational performance and maternal behaviors are highly responsive to the energy supply. When a reproductive attempt is made, changes in hormone secretion have dramatic effects on the partitioning and utilization of metabolic fuels. During ovulatory cycles and pregnancy, the ovarian steroids, estradiol and progesterone, induce coordinated changes in the procurement, ingestion, metabolism, storage, and expenditure of metabolic fuels. Estradiol can act in the brain to alter regulatory behaviors, such as food intake and voluntary exercise, as well as adenohypophyseal and autonomic outputs. At the same time, ovarian hormones act on peripheral tissues such as adipose tissue, muscle, and liver to influence the metabolism, partitioning and storage of metabolic fuels. During lactation, the peptide hormones, prolactin and growth hormone, rather than estradiol and progesterone, are the principal hormones controlling partitioning and utilization of metabolic fuels. The interactions between metabolic fuels and reproduction are reciprocal, redundant, and ubiquitous; both behaviors and physiological processes play vital roles. Although there are species differences in the particular physiological and behavioral mechanisms mediating nutrition-reproduction interactions, two findings are consistent across species: 1) Reproductive physiology and behaviors are sensitive to the availability of oxidizable metabolic fuels. 2) When reproductive attempts are made, ovarian hormones play a major role in the changes in ingestion, partitioning, and utilization of metabolic fuels. PMID- 1630735 TI - Introduction to premature rupture of membranes. AB - PROM is associated with controversies in diagnosis, management, and prognosis. The lack of a gold standard to confirm PROM makes it difficult to determine which diagnostic tool is the best and most reliable. It appears that the older methods of confirming PROM, which depend on properties inherent to amniotic fluid, are the best tools available today: ferning and nitrazine combined with patient history. PMID- 1630736 TI - Etiology of preterm premature rupture of membranes. AB - Numerous factors have been indicted as playing a role in causing preterm premature rupture of membranes (PPROM). After discussing the development of the amnion and chorion, this article focuses primarily on the effects that infection, nutrition, smoking, and cervical incompetence have on the fetal membrane and the subsequent advent of PPROM. However, evidence continues to support a multifactorial etiology for this entity, with numerous factors acting in concert. PMID- 1630737 TI - Neonatal morbidity and mortality secondary to premature rupture of membranes. AB - PROM is one of the most common complications of pregnancy that has a major impact on neonatal mortality and morbidity. The occurrence of PROM is either directly or indirectly responsible for a large number of premature births and the concomitant mortality and morbidity associated with preterm delivery. PROM turns a pregnancy into a high-risk situation and increases the need for neonatal resuscitation in the delivery room. The incidence of neonatal sepsis increases with PROM, but the overall outcome of the neonate, even with surfactant therapy, is still primarily dependent on the gestational age at the time of delivery. This is most relevant between 24 and 27 weeks' gestation. During this 3-week interval, survival improves by almost 2% for each additional day of in utero maturation (i.e., from 35 to 75%). Thus the benefit to the fetus of prolonging the pregnancy in cases of PROM is immensely worthwhile and should be aggressively pursued as long as there is no significant increase in maternal morbidity. PMID- 1630739 TI - Expectant and active management of preterm premature rupture of membranes. AB - Optimal management of PPROM remains controversial. Expectant management is a viable alternative only if there is no evidence of infection, advanced labor, or fetal distress. In these cases, aggressive intervention is appropriate, regardless of gestational age. The goal of expectant management is the achievement of increased gestational age at the time of delivery, given the tremendous potential advantage to be gained during the period between 26 and 34 weeks' gestation, an interval during which perinatal mortality decreases sharply. The potential value of corticosteroids and prophylactic antibiotics is discussed elsewhere in this issue. The power limitations of the previous studies, which considered amniocentesis and tocolytic therapy, preclude firm conclusions and enthusiastic recommendation for their routine inclusion in the expectant management of PPROM. PMID- 1630738 TI - Tests of fetal well-being in premature rupture of membranes. AB - In summarizing the published data on the use of amniocentesis and fetal biophysical assessment in managing patients with PROM the following conclusions may be drawn: 1. Both amniocentesis and fetal biophysical assessment are reasonably good methods to predict the fetus who is doing well and could therefore safely remain in utero, as well as the fetus who is at high risk for developing sepsis and therefore in need of delivery. 2. Consideration of routine transabdominal amniocentesis for Gram stain and cultures in patients with PROM is reasonable. Measurements of glucose levels, esterase activity, or cytokines are only investigational, and their use in patient management cannot be advocated at this time. 3. Although there are no prospective controlled randomized trials to prove improved pregnancy outcome by the use of either amniocentesis or frequent biophysical assessment, nonrandomized comparative trials as well as trials using historic controls suggest that the use of either or both techniques in combination may be beneficial in managing PROM. PMID- 1630740 TI - Corticosteroids after preterm premature rupture of membranes. AB - A review of all relevant randomized controlled trials provides strong evidence that corticosteroid therapy causes a significant reduction in respiratory distress syndrome (RDS) in preterm babies overall. This reduction in RDS is accompanied by a reduced incidence of neonatal death, intraventricular hemorrhages, and necrotizing enterocolitis. These benefits are also seen in cases of PROM. Corticosteroid therapy in PROM is associated with a trend toward an increase in neonatal infection. PMID- 1630742 TI - Management of premature rupture of membranes before 26 weeks' gestation. AB - PROM occurring before 26 weeks' gestation is associated with significant maternal morbidity as well as neonatal morbidity and mortality. With aggressive expectant management, neonatal survival can be predicted for a 23% and 54% incidence of patients with PROM at or less than 22 weeks' and 23 to 26 weeks' gestation, respectively. Of those neonates who survive, 55% to 69% will be neurologically intact on long-term follow-up. Conservative management leading to prolonged latency provides the neonate with the greatest potential for survival as outcome generally reflects the gestational age at birth. However, lethal pulmonary hypoplasia may occur with prolonged leakage and oligohydramnios. The patient who wishes to pursue a course of expectant management should be monitored closely for signs of infection and labor. Expectant management should be undertaken in a facility with resources capable of caring for the mother at risk of significant morbidity and the very low birth weight neonate. Ongoing counseling and psychologic support are essential in the management of this morbid pregnancy complication. PMID- 1630741 TI - Use of antibiotics for preterm premature rupture of membranes. Rationales and results. AB - PPROM is directly associated with 30% to 40% of preterm births. Reproductive tract infection, inflammation, or both may be primary causes or occur secondarily after PPROM and hasten the onset of labor. Recent carefully controlled trials demonstrate that antibiotic treatment (erythromycin, ampicillin) can significantly lengthen the "beneficial latency period" and reduce perinatal and maternal morbidity, as well as the costs. PMID- 1630743 TI - Management of premature rupture of membranes at term. AB - Although prelabor rupture of membranes at term is common, in most cases, the spontaneous onset of labor relieves the obstetrician of the need for making management decisions. The standard practice in the United States has been to induce labor with intravenous oxytocin in that minority of patients who fail to labor spontaneously. Controlled trials suggest that this practice is associated with higher rates of both chorioamnionitis and the need for cesarean delivery than is expectancy. Expectancy, however, has not been demonstrated to be safer for the perinate. PMID- 1630744 TI - New technologies for the management of preterm premature rupture of membranes. AB - The catheterization described is still incomplete, posing many problems yet to be solved. However, this method has shed light on new issues, including the intraamniotic administration of antibiotics against amniotic fluid infection and fetal infection, amnioinfusion of saline for oligohydramnios, and development of artificial amniotic fluid. These issues are much easier than the nursing of extremely small premature babies and should be solved by the collective wisdom of obstetricians. PMID- 1630745 TI - Antenatal care of the patient with previous preterm premature rupture of membranes. AB - Although there is a 21% recurrence risk for PPROM, little research has been directed to the obstetric management of women with prior PPROM. This article reviews indirect information regarding risk assessment, diet, lifestyle factors, and infections. A management plan is suggested. PMID- 1630747 TI - Avoiding litigation. Oral surgery in the 1990s. PMID- 1630748 TI - Oral surgery. From dark beginnings to a bright future. PMID- 1630746 TI - Pulmonary hypoplasia and deformations related to premature rupture of membranes. AB - In summary, fetal pulmonary development occurs in three phases. Hypoplasia results when an interruption occurs in or before the canalicular stage. Factors necessary for normal lung growth include sustained adequate amniotic fluid volume and normal fetal breathing movements. Pulmonary hypoplasia is most likely to occur with a very early rupture of membranes (less than 22 weeks) and with persistent oligohydramnios. Lack of sustained breathing movements and failure of modulation of ductal flow are strongly associated. Ultrasound measurement of fetal lung length may eventually be useful in monitoring intrauterine pulmonary development. Limb contractures resulting from prolonged oligohydramnios are examples of deformation-type defects. Their presence correlates most strongly with the length of the latent period (time from ROM to delivery) and the degree of oligohydramnios. Most contractures of this type are readily reversible. Early amnion rupture sequence, presumed to result from rupture of only the amnion in the first trimester, is associated with multiple severe fetal deformations. It usually occurs sporadically, with a minimal recurrence risk. PMID- 1630749 TI - Servicing the underserviced. A history of dental public health in Ontario. PMID- 1630750 TI - The rights of children to accept or refuse dental care. PMID- 1630751 TI - The treatment of enamel lesions. A CINOT perspective. PMID- 1630752 TI - Periodontal treatment planning. The influence of osseointegrated dental implants. PMID- 1630753 TI - Mucogingival considerations in orthodontics. PMID- 1630754 TI - Chronicles of dentistry. A former editor recalls his days at the journal's helm. PMID- 1630756 TI - Dentistry in the 1990s. Observations and options for the future. PMID- 1630755 TI - Dr. George Van Nest Relyea and the founding of the Ontario Dental Association. PMID- 1630758 TI - Digital diagnosis and disposable dam clamps. A look at technological advances in endodontics. PMID- 1630757 TI - Current developments in the filling of root canals. PMID- 1630759 TI - Corneal edema induced by cold. AB - We report on a patient, who regularly developed reversible corneal edema of the right eye after cold stress. Cycling tours in cold weather and windy conditions seemed to precipitate the edema. After a provocation test, we also observed transient, corneal edema. A few reports in the literature suggested that Raynaud's disease or trigeminal neuropathy might be responsible for cold-induced corneal opacification. None of these conditions was present in our patient, as proved by laboratory tests and magnetic resonance imaging. We found that contact lenses were an effective prophylaxis against corneal edema. PMID- 1630760 TI - Cilioretinal arteries in conjunction with a pit of the optic disc. AB - Cilioretinal arteries were noted to accompany pits of the optic disc in 16 of 25 cases (64%). Fourteen of the 16 cases were found to have 2 cilioretinal arteries (86%). The cilioretinal arteries were directly related to the pit of the disc and emerged either from the bottom or the margin of the pit in a proportion of 86%. This finding reinforces the assumption that the optic disc pit belongs to the same spectrum of congenital anomalies which also includes optic disc coloboma, megalopapilla and morning glory syndrome. A fluorescein angiography study showed hyperfluorescence of the pit in 12/16 cases and in particular in all the cases in which both cilioretinal arteries emerged from the pit. Hypofluorescence was noted in 7/9 cases in which the pit was not associated with cilioretinal arteries. Our findings could support the view that hyperfluorescence of the pit, which is not a constant phenomenon, mostly depends on the presence of cilioretinal arteries emerging from the pit. PMID- 1630761 TI - Surgical techniques and visual prognosis in retinal detachment due to macular hole. AB - In 250 eyes with retinal detachment due to macular hole, the visual prognosis of each surgical technique was evaluated. (1) Macular diathermy adversely affected the visual prognosis. (2) Macular buckling+macular diathermy produced a poorer visual prognosis than macular buckling alone. (3) The visual prognosis resulting from gas tamponade alone or vitrectomy+gas tamponade was better than that resulting from macular diathermy. It is not clear whether there is a significant difference in visual prognosis between gas tamponade alone and vitrectomy+gas tamponade. (4) Macular laser photocoagulation does not adversely affect the visual prognosis. Judging from these results, gas tamponade, which has the possibility of better visual prognosis and less operation stress, should be selected as the initial technique. PMID- 1630762 TI - The pupillary light reflex. 1. Age-dependent and age-independent parameters in normal subjects. AB - A hundred and three normal subjects (14-75 years old) were examined with a modified infrared TV videopupillometer that had previously been developed. Maximal pupillary diameter (p less than 0.00001), pupillary diameter in percent of iris diameter (p less than 0.00001), maximal pupillary area (p less than 0.00001), latency time of the light reflex (p less than 0.00001), maximal contraction velocity (p less than 0.00002), contraction velocity at 1 s (p less than 0.00001) and dilatation velocity at 6 s (p less than 0.0001) are strongly age dependent. A statistical formula is given to allow the calculation of the exact percentile for every parameter. Parameters which are age independent if they are expressed in percent of the maximal pupillary area are contraction velocity at 1 s (r = 0.042, p = 0.68) and dilatation velocity at 6 s (r = -0.150, p = 0.13). They can be used if age-matched study groups are not available. Furthermore, it is shown that most parameters of the pupillary light reflex correlate significantly with each other. The highest correlations are found with the maximal pupillary area. Differences between sexes are not evident. It is thought that this infrared videopupillometry and the given data base are useful for further clinical studies to investigate the autonomic nervous system. PMID- 1630763 TI - The pupillary light reflex. 2. Prevalence of pupillary autonomic neuropathy in diabetics using age-dependent and age-independent pupillary parameters. AB - Seventy-seven diabetics with a duration of the disease ranging from 2 to 55 years (average 18.5 years) were studied with infrared videopupillometry. The prevalence of diabetic autonomic neuropathy at the pupillary control system (pANP) was studied comparatively using several pupillary tests. The average prevalence using age-dependent parameters was 30.2% [maximal pupillary area: 22.1%, maximal contraction velocity: 24.7%, contraction velocity at 1 s (CV1): 28.6%, and dilation velocity at 6 s (DV6): 45.5%]. Comparing these percentages to prevalences of other diabetic late complications, e.g. retinopathy (49.4%), DV6 seems to be good for the diagnosis of pANP. If CV1 and DV6 are expressed in percent of the maximal pupillary area (CV1% and DV6%), they become age independent. The average CV1% and DV6% of diabetics differ highly significantly from those of normals (CV1%: 58.6 +/- 14.5 vs. 64.1 +/- 6.4%, 2 p less than 0.005, and DV6%: 6.0 +/- 2.9 vs. 7.3 +/- 1.1%, 2 p less than 0.001). The average prevalence of pANP using these age-independent parameters was 25.4%. These data suggest that the prevalence of pANP, especially disorders of pupillary dilation (DV6), is high in long-standing diabetes. Furthermore, CV1% and DV6% have proved to be valid parameters in finding differences in the light reflex in non-age matched study groups. PMID- 1630764 TI - C wave of electroretinogram and visual evoked response in optic neuritis due to demyelinating diseases. AB - In 21 consecutive cases with unilateral optic neuritis due to demyelinating disease, ERG, C wave of ERG and VER were recorded and studied in both eyes. Also 8 cases suffering from optic atrophy due to trauma or glaucoma were included. The analysis of data shows that the C-wave is significantly diminished in both eyes, namely the affected and the sound, in the cases of optic neuritis. Also in comparison to VER, C wave has a comparative probability in diagnosing optic neuritis due to demyelinating disease. The C wave of ERG is normal in the cases of optic atrophy. The mechanism of C wave involvement during the course of demyelinating disease may be related with an abnormality of the ionic homeostasis of the subretinal space. PMID- 1630765 TI - Effects of elastase on cultured human trabecular meshwork. AB - We evaluated the effect of elastase, a proteolytic enzyme, on the endothelial meshwork of cultured human trabecular meshwork using a solid agar method. The tissues were obtained from 3 postmortem eyes, aged 64, 71 and 77 years. Elastase was added to the culture medium for 24 h at a concentration of 1 x 10(-1)-10(-4) mg/ml. The cultured specimens were then processed for transmission electron microscopy. We evaluated the electron micrographs to determine the percent area occupied by the cells and the extracellular materials and by the empty space in the endothelial meshwork using computer-assisted morphometry. A statistically significant decrease in extracellular materials with intact trabecular cells was confirmed 24 h following the administration of elastase at the concentration of 1 x 10(-1)-10(-3) mg/ml. PMID- 1630766 TI - Xanthogranuloma juvenile--a rare cause of orbital swelling in adulthood. AB - Juvenile xanthogranuloma, a non-Langerhans-type benign proliferation, in adulthood is a rare condition. This article reports the second known case in the western literature of solitary orbital involvement. The diagnosis was confirmed by orbital biopsy, and symptoms were dramatically relieved by corticoids, although a relapse occurred after their withdrawal. The importance of differentiating benign conditions from malignancies is discussed. PMID- 1630767 TI - Beta irradiation of pterygium. PMID- 1630768 TI - Zinc supplements: are there ophthalmologic indications? PMID- 1630769 TI - Beta irradiation of pterygium. PMID- 1630770 TI - Treatment of rheumatoid corneal ulcers. PMID- 1630771 TI - Vision screening and children's access to eye care. PMID- 1630772 TI - Results of inpatient and outpatient cataract surgery. A historical cohort comparison. AB - PURPOSE: The transition from inpatient to outpatient cataract surgery during the last decade was not accompanied by prospective investigation of its effect on visual outcomes or surgical complications. The authors performed this study to assess the impact of this transition on surgical results. METHODS: The authors reviewed 600 extracapsular cataract extractions performed by 4 experienced ophthalmic surgeons during a 36-month period; in 300 cases, patients were hospitalized after surgery (inpatient group), and, in 300 cases, patients were never hospitalized (outpatient group). The same surgical techniques were used in all cases. Visual outcome and rates for operative and postoperative complications were compared. RESULTS: There were no statistically significant differences between the inpatient and outpatient groups for visual acuity. Excluding patients with pre-existing nonlenticular ocular disease, a best-corrected visual acuity of 20/40 or better was achieved in 93.1% of inpatient cases and in 97.2% of outpatient cases 6 months after surgery. Postoperative, clinically apparent cystoid macular edema was more common in the inpatient group (P = 0.03); however, after exclusion of patients with diabetes, hypertension, age younger than 65 years, and eyes with pre-existing nonlenticular disease, there was no statistically significant difference between groups. No significant differences in rates for other operative and postoperative complications were identified, including wound dehiscence, unplanned postoperative filtering blebs, infectious endophthalmitis, retinal detachment, persistent iridocyclitis, glaucoma, and corneal edema. CONCLUSION: This study does not demonstrate that the transition to outpatient cataract extractions has had an adverse effect on surgical outcomes. PMID- 1630773 TI - A prospective, randomized, double-masked comparison of a zonal-progressive multifocal intraocular lens and a monofocal intraocular lens. AB - INTRODUCTION: Multifocal intraocular lenses (IOLs) have been designed to provide improved near visual acuity without spectacles compared with monofocal IOLs. Early studies have reported variables amounts of decreased visual acuity and contrast sensitivity with multifocal IOLs, and some patients have experienced halos and glare. METHODS: The authors performed a prospective, double-masked, multicenter evaluation of 62 patients randomized between a new zonal-progressive optic multifocal IOL and a monofocal IOL. RESULTS: Mean postoperative spherical equivalent, astigmatism, and uncorrected and best-corrected distance visual acuity were similar between the two groups. Patients with a multifocal IOL achieved significantly better uncorrected near visual acuity than patients with monofocal IOLs (J3+ versus J7; P less than 0.0001). With distance correction only, mean near visual acuity was J2 versus J5- (P = 0.0001). Best-corrected near visual acuity was J1 for both groups, with 1.36 diopters (D) for the multifocal group versus 2.37 D for the monofocal group (P less than 0.0001). Regan contrast sensitivity was lower for the multifocal patients at all contrast levels, and achieved statistical significance at very low contrast (11% contrast; P = 0.0024). Fifty-two percent of patients with a multifocal IOL reported that they did not need spectacles at all or used them only for their fellow eye, compared with 25% of the patients with monofocal IOLs. CONCLUSION: Both monofocal and multifocal implant patients were very satisfied with the results of their cataract extraction and IOL implant surgery. A small loss of contrast sensitivity with the multifocal IOL was demonstrated, consistent with theoretical predictions. The functional significance of the loss of contrast sensitivity appears to be small and counterbalanced by the advantage of improved uncorrected near visual acuity. PMID- 1630774 TI - Penetrating ocular fish-hook injuries. Surgical management and long-term visual outcome. AB - BACKGROUND: Ocular penetrating fish-hook injuries represent a rare yet potentially devastating ocular trauma. To date, only five cases have been reported in the medical literature. The authors present five new cases with long term follow-up. METHODS: All individuals who presented to the Wilmer Ophthalmological Institute emergency room with ocular fish-hook injuries between 1974 and 1990 were identified, and ophthalmic follow-up evaluations were performed. RESULTS: Individuals were male, between the ages of 10 and 27, with follow-up evaluation of 2.0 to 15.5 years (mean, 6.7 years). The left eye was involved in 80% and in no instance had a single hook penetrated the lid and globe simultaneously. Initial visual acuity was uniformly poor (20/200 or worse). Using specialized surgical techniques, ultimate visual outcome was excellent in 80% of cases (4 of 5 with visual acuity of 20/30 or better). One eye was enucleated because of panendophthalmitis after delayed wound closure. Similar overall results are achieved when previous reports are included in the analysis (90% with visual acuity of 20/40 or better). CONCLUSIONS: These results suggest that penetrating ocular fish-hook injuries may have an excellent long-term prognosis if prompt, appropriate surgical intervention is accomplished. PMID- 1630775 TI - Shotgun eye injuries. Ocular risk and eye protection efficacy. AB - BACKGROUND: Little is known about the efficacy of shotgun eye protection. Shotguns can easily propel pellets with enough energy to penetrate the human eye, and a large percentage of shotgun eye injuries occur during shotgun sports such as hunting, trap, skeet, and sporting clays. Many of these injuries are preventable with proper eye protection. Although it is known that polycarbonate is the best lens material for shotgun eye protection, there has been no research that addresses the vision protective system design and its influence on eye protection. METHODS: A field study was performed during which shotshells were fired at 1:1 scale photographs of human faces to determine the risk of ocular trauma. The protective efficacy of three types of polycarbonate protective eye wear (standard industrial safety glasses with snap-on side shields, wrap-around racket sport glasses, and three-piece glasses with integral side shields) was tested by firing shotshells at them at various distances. Both frontal and side protection was evaluated. RESULTS: Results showed that the eye is at a high risk (55% to 100%) of being hit with shot pellets at ranges of 15 to 40 yards. It also was determined that the protective eye wear will give good frontal eye protection from shotgun pellets but integral side shields and a headband are necessary to obtain adequate side protection. CONCLUSION: These findings, coupled with the poor visual prognosis of ocular shotgun injuries, indicate that polycarbonate protective eye wear with integral side shields and headbands should be worn by all involved with shotgun sports. PMID- 1630776 TI - Corneal epithelial permeability of dry eyes before and after treatment with artificial tears. AB - PURPOSE: The question of whether artificial tears can lead to objective improvement of ocular surface disease in dry eyes is still unanswered. The aim of the current study is to assess the influence of artificial tears on corneal epithelial permeability of dry eyes. Furthermore, the effect of benzalkonium chloride, used as a preservative of artificial tears, on corneal epithelial permeability is investigated. METHODS: The corneal epithelial permeability of 40 dry eye patients (80 eyes) was measured by computerized objective fluorophotometry before and 6 weeks after treatment with artificial tears containing either polyvinyl pyrrolidone 2% without preservative (20 patients) or polyvinyl pyrrolidone 2% preserved with benzalkonium chloride 0.005% (20 patients). RESULTS: Before treatment, the epithelial permeability of the dry eye patients was found to be 2.7 times that of a control group. After treatment, the epithelial permeability of patients treated with unpreserved polyvinyl pyrrolidone 2% had decreased significantly (-37%; P less than 0.001), whereas patients who had been treated with polyvinyl pyrrolidone 2% preserved with benzalkonium chloride 0.005% showed an increase in epithelial permeability (+21%; P = 0.05%). CONCLUSION: These data suggest that, in dry eyes, treatment with unpreserved artificial tears may lead to an objective improvement in corneal surface disease. However, this effect may be counteracted by preservation of tear substitutes with benzalkonium chloride. PMID- 1630777 TI - New developments in serologic screening of corneal donors for HIV-1 and hepatitis B virus infections. AB - PURPOSE: The authors evaluated different methods to serologically screen potential cadaveric corneal donors for human immunodeficiency virus type 1 (HIV 1) and hepatitis B virus (HBV) infections. METHODS: Three commercially available enzyme-linked immunosorbent assays (ELISAs) for antibodies against HIV-1, a supplemental ELISA test for HIV antigen, and a radioimmunoassay and two ELISAs for hepatitis B surface antigen were compared using serum from cadavers with acquired immune deficiency syndrome (AIDS), cadavers with high risk factors for HIV infection, and cadavers with no known risk of HIV infection, along with respective confirmatory testing. RESULTS: The ELISA tests for HIV antibodies from Abbott Laboratories, Electro-nucleonics, and Organon-Teknika showed sensitivities of 94.3%, 94.3%, and 97.1%, respectively, compared with the autopsy diagnosis of AIDS in 35 cadavers. The sensitivities of the HIV-1 antibody ELISAs ranged between 73% and 87% compared with positive Western blots in testing 118 sera from cadavers at high risk of HIV-infection, but not manifesting AIDS at the time of death. Supplemental ELISA testing for HIV-1 antigen, in an effort to close the seronegative window, failed to identify any HIV antigen-positive sera confirmed by neutralization that were not also positive for antibodies to HIV-1 by ELISA and Western blot. The ELISA for HBV surface antigen had an overall sensitivity of 92.9% and specificity of only 81.3% compared with radioimmunoassay in testing 409 sera. Monoclonal ELISAs for HIV-1 antigen and HBV surface antigen paradoxically had lower specificity than polyclonal ELISAs, with false positivity correlating with hemolysis and with increasing death to puncture time. CONCLUSION: ELISA testing for antibodies against HIV-1 is relatively but not absolutely effective, should be accompanied by historical screening for risk factors, and does not appear to benefit from supplemental ELISA testing for HIV-1 antigen. ELISA testing for HBV surface antigen has lower specificity in screening cadaveric sera when compared with radioimmunoassay. PMID- 1630778 TI - Evaluation of corneal collagen shields as a drug delivery device for the treatment of experimental Pseudomonas keratitis. AB - PURPOSE: To clarify the role of corneal collagen shields as a drug delivery device for the treatment of bacterial keratitis, the authors studied the effectiveness of topical gentamicin treatment, with and without the use of corneal collagen shields, in a rabbit model of Pseudomonas keratitis. METHODS: Forty-eight New Zealand white rabbits were infected by injecting 500 colony forming units (CFU) of Pseudomonas aeruginosa into the corneal stroma, and treatment was begun 24 hours later. A 13.6 mg/ml solution of gentamicin was topically administered during a 24-hour period. Collagen shields were soaked in gentamicin 13.6 mg/ml for 5 minutes before placing them on the cornea. Corneas were quantitatively cultured 1 hour after the treatment period ended. Six different groups of rabbits were tested, with the results analyzed as the mean log10 of bacterial CFU. RESULTS: An untreated control group had significantly more bacteria (7.96 +/- 0.74) than any of 5 treatment groups. No difference was found between groups given a loading dose of antibiotic drops at the beginning of treatment, either with (4.90 +/- 2.41) or without (6.25 +/- 0.54) an antibiotic impregnated collagen shield. A group treated with a collagen shield augmented with gentamicin drops every 3 hours had fewer bacteria (1.52 +/- 1.82) than a group receiving drops alone (4.15 +/- 1.83) (P less than 0.05). However, treatment with a collagen shield supplemented with drops every 3 hours was not as effective as gentamicin drops administered every 30 minutes (no bacterial growth) (P less than 0.05). CONCLUSION: These results show that antibiotic-impregnated collagen shields should not replace traditional antibiotic drop therapy as the mainstay of treatment but may be a useful adjunct to treatment with topical antibiotics. PMID- 1630779 TI - Corneal wound healing after excimer laser ablation. Effects of nitrogen gas blower. AB - PURPOSE: To examine the effects of blowing nitrogen gas over the cornea during photorefractive keratectomy. METHODS: Excimer laser ablations for myopia were performed on rabbit corneas with or without the blowing of nitrogen across the surface of the cornea. All eyes underwent a 5-diopter myopic ablation; in 8 eyes, a ring was used to blow nitrogen gas across the cornea, and, in 8 eyes, the same ring was used, but no nitrogen gas was blown. RESULTS: Epithelial healing occurred more rapidly in the eyes that were not treated with the gas (3.8 +/- 1.3 days) than in the gas-treated group (6.1 +/- 0.8 days; P = 0.0025). Corneal haze was greater in the group treated with gas. Results of histologic examination showed the ablated area to have a smoother surface when nitrogen was not blown across the cornea surface. CONCLUSION: Superficial corneal deturgescence produced by the nitrogen gas appears to result in a rougher surface immediately postoperatively with undesirable effects on surface healing, but further studies will be necessary to determine the applicability of these results to humans. PMID- 1630780 TI - Blood-aqueous barrier in eyes with retinal vein occlusion. AB - PURPOSE: The purpose of this study is to examine the changes of blood-aqueous barrier function in cases of central or branch retinal vein occlusion. METHODS: In addition to fluorophotometry of the aqueous humor and posterior vitreous, the authors used a method that quantifies protein in the aqueous (aqueous flare) by measuring the intensity of scattered laser light. RESULTS: Aqueous and posterior vitreous fluorescein concentrations and aqueous flare were significantly higher than in unaffected fellow eyes or eyes of visually normal age-matched controls both in central and branch retinal vein occlusions. They also were significantly higher in eyes with central vein occlusion than in those with branch vein occlusion. Among those eyes with central vein occlusion, aqueous and posterior vitreous fluorescein concentrations and aqueous flare were significantly higher in the hemorrhagic than in the venous stasis type of disease. Among eyes with branch vein occlusion, cases at the acute stage showed significantly higher amounts of aqueous and posterior vitreous fluorescein concentrations and aqueous flare than did those with chronic occlusion. CONCLUSION: The authors believe that increased amounts mainly reflect blood-ocular barrier disruption. Not only the blood-retinal barrier but also the blood-aqueous barrier disruption is a common sequela in the disorder. PMID- 1630781 TI - Macular capillary hemodynamic changes associated with Raynaud's phenomenon. AB - BACKGROUND: Raynaud's phenomenon is an episodic, reversible spasm of the digital arterioles. Previous studies have suggested that Raynaud's phenomenon may be associated with alterations in the ocular circulation. The authors used the blue field entoptic simulation technique to study macular retinal capillary hemodynamics in patients with Raynaud's phenomenon. METHODS: Forty-two volunteers participated in the study: 18 with a connective tissue disease and secondary Raynaud's phenomenon, 8 with a connective tissue disease and no Raynaud's phenomenon, and 16 healthy volunteers. The mean of three blue field entoptic density and velocity measurements was determined before as well as during and 10 minutes after the immersion of one hand in ice water. RESULTS: Patients with severe Raynaud's phenomenon demonstrated a statistically significant 30% decrease in retinal capillary flow during immersion of a hand in ice water (P less than 0.05), which remained 17% reduced (P less than 0.05) for at least 10 minutes after removal. The decrease in capillary flow was not observed in control individuals or in individuals with connective tissue disease who demonstrated minimal or no Raynaud's phenomenon. CONCLUSION: The prolonged reduction in retinal capillary flow observed in subjects with Raynaud's phenomenon is probably caused by retinal arteriolar vasoconstriction and is similar to concurrent arteriolar vasoconstriction reported in other systemic vascular beds. In the retina, the recurrent ischemic episodes may result in dysfunction or injury. PMID- 1630782 TI - Trimethoprim-sulfamethoxazole therapy for ocular toxoplasmosis. AB - BACKGROUND: Toxoplasmosis is a leading cause of retinochoroiditis. Conventional multidrug therapy using sulfadiazine, pyrimethamine, and folinic acid is increasingly difficult to procure and administer safely. METHODS: To evaluate the efficacy of trimethoprim-sulfamethoxazole, a fixed-combination antibiotic, patients with active toxoplasmosis were treated with trimethoprim sulfamethoxazole (Bactrim DS) with or without adjunctive clindamycin and prednisone for 4 to 6 weeks. RESULTS: All patients in this study (n = 16) had resolution of active retinochoroiditis and had improved vision, with an average gain of 5.2 lines of vision. Two patients developed a drug allergy. CONCLUSION: Trimethoprim-sulfamethoxazole appears to be a safe and effective substitute for sulfadiazine, pyrimethamine, and folinic acid (Leucovorin) in treating ocular toxoplasmosis. PMID- 1630783 TI - Alcohol consumption and the prevalence of diabetic retinopathy. AB - OBJECTIVE: To determine if alcohol consumption is associated with the prevalence of diabetic retinopathy. PARTICIPANTS: This study surveyed a population-based sample (n = 1210) of younger-onset diabetic persons (diagnosed before age 30 years and taking insulin) and a stratified random sample (n = 1780) of older onset diabetic persons (diagnosed after age 30 years). Baseline and 4-year follow up examinations completed by 996 and 891 (730 by persons age 21 or older) younger onset persons, respectively, and 1370 and 987 older-onset persons, respectively. Data analyzed are from the 4-year follow-up examination. Questionnaires concerning consumption were completed at follow-up. MAIN OUTCOME MEASURE: Diabetic retinopathy as determined from stereographic fundus photography. RESULTS: After controlling for known risk factors in the adult younger-onset group, average alcohol consumption, as determined by questionnaire, was inversely associated with prevalence of proliferative diabetic retinopathy (PDR), odds ratio, 0.49; 95% confidence interval, 0.27 to 0.92. The trend was similar for recent consumption, odds ratio, 0.63; confidence interval, 0.37 to 1.09. In the older-onset groups taking or not taking insulin, average or recent alcohol consumption or usage history were not significantly associated with the prevalence of any retinopathy or PDR. CONCLUSIONS: Alcohol consumption does not appear to increase the risk of retinopathy and may have a beneficial effect in younger-onset persons, although further study is needed. PMID- 1630784 TI - Prevalence of age-related maculopathy. The Beaver Dam Eye Study. AB - PURPOSE: The relationships of retinal drusen, retinal pigmentary abnormalities, and macular degeneration to age and sex were studied in 4926 people between the ages of 43 and 86 years who participated in the Beaver Dam Eye Study. METHODS: The presence and severity of various characteristics of drusen and other lesions typical of age-related maculopathy were determined by grading stereoscopic color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System. RESULTS: One or more drusen were present in the macular area of at least 1 eye in 95.5% of the population. People 75 years of age or older had significantly higher frequencies (P less than 0.01) of the following characteristics than people 43 to 54 years of age: larger sized drusen (greater than or equal to 125 microns, 24.0% versus 1.9%), soft indistinct drusen (23.0% versus 2.1%), retinal pigment abnormalities (26.6% versus 7.3%), exudative macular degeneration (5.2% versus 0.1%), and geographic atrophy (2.0% versus 0%). CONCLUSION: These data indicate signs of age-related maculopathy are common in people 75 years of age or older and may pose a substantial public health problem. PMID- 1630786 TI - Clinical experience with the surgical removal of subfoveal neovascular membranes. Short-term postoperative results. AB - BACKGROUND: Severe visual loss occurs in the presumed ocular histoplasmosis syndrome (POHS) and in age-related macular degeneration (ARMD) from subfoveal neovascularization. Although laser photocoagulation has recently been recommended for this complication in ARMD, treatment is inevitably associated with a loss of central vision. In an attempt to restore and/or preserve central vision, the authors undertook surgical removal of subfoveal neovascular membranes in these diseases. METHODS: Patients with POHS and ARMD with reduced Snellen visual acuity to 20/80 or less were selected if there was angiographic evidence of a neovascular membrane beneath the fovea. Modern vitreoretinal techniques were used to remove the subfoveal neovascular complex. RESULTS: The authors' first 15 patients with POHS and 19 patients with ARMD were followed for an average of 4 months postoperatively. Snellen visual acuity improved by 2 lines or more in 8 of 15 (53%) cases of POHS. Although similar improvements in Snellen visual acuity were not observed in cases of ARMD, 14 of 19 (74%) cases showed either slight improvement or stabilization of their vision postoperatively. Complications included recurrent neovascularization in 2 of 15 (13%) and 3 of 19 (16%) eyes with POHS and ARMD, respectively. No retinal detachment or preretinal proliferation was observed. CONCLUSIONS: These results suggest that subfoveal neovascularization can be successfully removed with preservation of foveal vision in POHS and stabilization in ARMD, at least for the short term. Visual improvement was observed in POHS even after 6 months of decreased vision. Finally, visual prognosis is most dependent on the integrity of the subfoveal RPE after removal of the membrane. PMID- 1630785 TI - Extramacular disciform lesions simulating uveal tumors. AB - PURPOSE: The purpose of this study is to identify clinical, ultrasonographic, and fluorescein angiographic features of extramacular disciform lesions that allow differentiation from uveal tumors. METHODS: This was a retrospective study of 19 patients referred to our ocular oncology unit with a possible malignancy who had a diagnosis of an extramacular disciform lesion made after complete evaluation. RESULTS: The level of accuracy for each diagnostic technique alone was as follows: clinical (79%), ultrasonography (83%), and angiography (83%). Fluorescein angiography had limited utility because of severe media opacities in seven cases. No tumor developed an intraocular malignancy during the follow-up period. CONCLUSION: A combination of the above, noninvasive techniques can be used to correctly diagnose extramacular disciform lesions. PMID- 1630787 TI - Clinicopathologic spectrum of primary uveal melanocytic lesions in an animal model. AB - BACKGROUND: Currently, there are no animal models of primary uveal melanoma in an eye large enough to allow documentation of the clinical evolution of the lesion by either funduscopy or fundus photography. METHODS: The authors induced primary uveal melanocytic lesions in the eyes of Dutch (pigmented) rabbits using a two stage carcinogenesis protocol involving initiation with 4 weekly topical applications of 10 microliters of a 1% solution of 7,12-dimethyl benz[a]anthracene (DMBA) in acetone (21 eyes) followed by 12 weekly topical applications of a 10 microliters solution of either 0.25% or 0.5% croton oil in acetone. They also investigated the effect of initiation with DMBA without promotion and the effects of chronic topical exposure to acetone and proparacaine. RESULTS: Exposure to DMBA followed by promotion with croton oil in either concentration was the most effective means of inducing clinically detectable fundus lesions. Histologically, a spectrum of melanocytic proliferations developed including benign nevi, nevi with varying grades of cytologic atypia, and clusters of confluent atypical melanocytes that may represent early melanomas. Although clinical regression of fundus lesions was noted in eight eyes after promotion had been stopped, five of these eyes showed unequivocal histologic evidence of a residual uveal melanocytic lesion. Chronic ocular irritation is capable of inducing cytologically benign subclinical uveal melanocytic proliferations. CONCLUSIONS: The conventional classification of human uveal melanocytic lesions includes only nevi and melanomas, but a comparison of the results of this study with descriptions of human uveal melanocytic nevi suggests the existence of a spectrum of intermediate atypical precursor lesions in humans. PMID- 1630788 TI - Intraocular and central nervous system lymphoma in a cardiac transplant recipient. AB - BACKGROUND: Although B-cell lymphomas are the most frequent cancers that evolve in transplant patients, histopathologic verification of intraocular lymphoma as a result of cyclosporine immunosuppression has not been previously recognized. METHODS: A complete autopsy was performed on a 67-year-old woman who died 33 months after orthotopic heart transplantation. FINDINGS: Large cell lymphoma extensively involved the anterior segment of the left eye, as well as the vitreous, retina, subretinal pigment epithelial zone, and optic nerve. Tumor also was found in the ipsilateral orbitofrontal cortex and hypothalamic areas. No systemic lymphoma was present. CONCLUSION: Ocular and central nervous system lymphoma developed in a heart transplant patient. In addition to opportunistic infections, ophthalmologists should be aware that opportunistic lymphoproliferative disorders involving the eye and brain can occur in these immunosuppressed individuals. Epstein-Barr virus infection has been implicated as playing a major role. PMID- 1630789 TI - Long-term results of adjustable suture surgery for strabismus secondary to thyroid ophthalmopathy. AB - PURPOSE: To review the results of adjustable suture surgery in patients with strabismus secondary to thyroid ophthalmopathy to determine long-term outcome and to identify postoperative complications. METHODS: The records of 1524 patients with thyroid ophthalmopathy were retrospectively reviewed to identify those who required treatment for strabismus in the ocular motility clinic. Treatment consisted of adjustable suture surgery, prisms, or both. Elimination of diplopia in primary and reading positions was used at the criterion for success. RESULTS: Forty-seven patients were treated with adjustable suture surgery, with an average follow-up of 41 months. Results after 1 or more surgeries were: 47% excellent, 26% good, 19% fair, and 9% poor. Significant postoperative complications included eyelid retraction and A-pattern exodeviation. Sixteen of 18 patients with fair or poor outcomes after the initial surgery were recognized within 6 months. Postoperative changes in vertical deviation from primary position to downgaze were predictive of postoperative diplopia in downgaze. Analysis of multiple preoperative characteristics showed no statistically significant associations with outcome. Eight additional patients had adequate relief of diplopia using prisms alone, with an average follow-up of 49 months. CONCLUSIONS: Long-term symptomatic relief of diplopia was obtained in the majority of patients using adjustable suture strabismus surgery, combined occasionally with small amounts of prism postoperatively. Prisms alone provided effective long-term relief in patients with small-to-moderate deviations. PMID- 1630790 TI - Negative predictive value of a population-based preschool vision screening program. AB - BACKGROUND: The Enhanced Vision Screening Program is a population-based vision screening program that has, at present, examined 59,782 children. Its main goal is to detect amblyopia, strabismus, and high refractive errors. An average of 11,910 4 1/2- to 5 1/2-year-old children are screened yearly. The current study determines the negative predictive value of the screening program: For a subject having passed the vision screening test, what is the probability of not having amblyopia, strabismus, or high refractive errors? METHODS: Of the 11,734 subjects who passed the vision screening, 200 were randomly chosen to undergo a strictly defined gold standard examination by an orthoptist and an ophthalmologist. RESULTS: Of the 200 randomly chosen subjects, 157 underwent the gold standard evaluation. The negative predictive value of the Enhanced Vision Screening Program was 97.6% for any potentially vision-threatening ocular condition. It was 98.7% if we considered only the visually significant ocular problems that the test was designed to detect. CONCLUSION: Because the negative predictive value of the Enhanced Vision Screening Program is not 100%, some children with amblyopia, strabismus, or refractive errors are missed. Occasionally, a rare, potentially vision-threatening condition may go undetected. Parents should be made aware of this when they receive the results of the vision screening. PMID- 1630792 TI - Lessons about quality from the IOM Report on Medicare. PMID- 1630791 TI - A revolution in understanding: how ethics has transformed health care decision making: the role of patient education. PMID- 1630793 TI - Medicare: a strategy for quality assurance, V: Quality of care in a changing health care environment. AB - This article, the fifth and final in a series, provides a retrospective wrap-up of an Institute of Medicine (IOM) study to develop a strategy for quality review and assurance in Medicare. Portions of that report were adapted for four articles in QRB in January, March, August, and October 1991. This final article reflects on selected developments in the period since the IOM report first appeared, particularly those involving other IOM activities, in the context of certain of the findings, conclusions, and recommendations of the IOM study committee on Medicare quality assurance. PMID- 1630794 TI - Inputs and outputs for coronary artery bypass grafting. PMID- 1630795 TI - A methodology for QI in the coronary artery bypass grafting procedure involving comparative process analysis. AB - This report describes an example of applying comparative process analysis to improve surgical procedures. This approach to health care quality improvement relies on combining techniques from the technical disciplines of systems analysis and systems engineering with concepts embodied in the philosophies of total quality management. Coronary artery bypass grafting (CABG) has been examined in a cooperative observational study involving an engineer, cardiac surgeons, perfusionists, nurses, and an anesthesiologist. A baseline process flow for the CABG procedure was developed, against which interinstitutional variations among the five participating medical centers have been identified. On the basis of analysis of the variations, efforts are under way to develop a strategy for incremental continuous improvement in the CABG procedure in each of the five institutions. On the basis of the perceived success of the first phase of the activity, a second phase, wider in scope, has been undertaken. PMID- 1630796 TI - Total quality management in a hospital. AB - The adaptation of the management philosophy and tools of total quality management (TQM) to the modern American hospital, its staff, and physicians is a major challenge facing health care today. The TQM "bandwagon" is one that hospitals both want to--and are required to--jump on, insofar as TQM is now part of the revised Joint Commission standards [Ed note: The standards encourage hospitals to adopt TQM, continuous quality improvement, or a similar approach to improve performance]. TQM holds out the promise of improving clinical quality while simultaneously reducing the "cost of poor quality." Although the actual realization of cost savings through TQM remains to be seen, the author provides an exceptionally clear overview of the issues involved in TQM implementation at the hospital level. This article is noteworthy in its practical and experienced approach to the necessary groundwork for a successful TQM program, including strategic commitment, human resource issues, and oversight of the TQM process as it unfolds. Quality review professionals may still wonder how to merge hospital and medical staff quality assurance efforts with TQM initiatives in the near future. PMID- 1630797 TI - Health care reform dominates "Health Agenda 1992" meeting. PMID- 1630798 TI - [Viral hepatitis '91]. PMID- 1630799 TI - [Advances in the diagnosis of non-A non-B viral hepatitis]. AB - Having constructed the serological diagnostics of Hepatitis A and B viruses there remained non identified agent(s): named "Non-A, non-B". The non-A, non-B infecting parenterally is a Flavivirus, with lipoid envelope and a diameter of 30 60 nm, as stated very early. After having known the simple filament RNS genome, named as Hepatitis C. In the same time it was tried to isolate the antigen and antibody from ill people, without success. There were not usable the surrogate markers too (anti-HBc and ALT). One part of the synthetized polypeptides from little fragments of C virus genome was apt to antibody-detection. In the acute state there was 20-40, in the chronic state 60-80% anti-HCV positive during the illness. This seropositivity is not equal of healing, neither the potency to infect. The infectivity is showed by the nucleic acid's presence (of the virus) in the blood (PCR), the perfect healing by the neutralizing antibody. PMID- 1630800 TI - [Polymerase chain reaction and its application]. AB - The polymerase chain reaction (PCR) is one of the most important new methods in molecular biology. It is widely used in genetic and anthropologic basic research, in oncology and virology, in all those fields, where molecular biologic methods can give answers to the questions raised. The procedure enables one to multiply with extreme precision targeted pieces of amounts as little as one target molecule of DNA or RNA by five to six logs, making them easy to be handled and examined by routine molecular biological methods. The method is presented through one possible application field, that is of great importance in the study of hepatocarcinogenesis. Sensitivity of PCR in detection of hepatitis B virus DNA is greater by four logs than animal inoculation, the last most sensitive method known. PMID- 1630801 TI - [Determination of hepatitis C antibodies, using the Abbott and the Ortho anti-HCV EIA kits, in chronic liver diseases and patients under hemodialysis for chronic renal failure]. AB - The diagnostic usefulness of anti HCV EIA test of Abbott and Ortho companies were compared. The anti HCV levels determined in the sera of 173 patients with chronic liver diseases and of 17 haemodialysed kidney patients. 109 of 190 (57%) sera were found to be negative and 81 (43%) positive determined by Abbott kit, while 127 (67%) were negative and 63 (30%) were positive by the Ortho kit. Positive results in patients with chronic liver disease were found in 66 patients by Abbott and 58 patients with Ortho Kit. Distribution of positive cases according to the diagnosis is as follows: 29 (57%) out of 51 chronic hepatitis, 17 (61%) out of 28 cirrhosis. Conflicting results were obtained in 20 cases of 190 (11%) when 17 sera were positive by Abbott and negative by ORTHO, and 3 sera were negative by Abbott, and positive by Ortho. The samples close to the cut off and with low positivity with conflicting results were checked again by the neutralization HCV EIA Abbott assay. We found the Abbott HCV EIA test more sensitive in our excellent for screening of large numbers of samples, we recommend to confirm the positive results by a neutralization type test. PMID- 1630802 TI - [Hepatitis B virus markers and anti-HCV antibodies in hemodialyzed patients]. AB - Serum samples from 155 patients on haemodialysis were examined for markers of hepatitis B and C. Abbott and Ortho Elisa tests were used for the determinations. ALT levels were analysed at the same time. Of the 345 random blood donors and 366 prisoners examined, 1.44% proved to be anti-HCV antibody positive. 13 medical staff workers of 147 were found to be positive for anti-HCV antibody (19.1%). In patients on chronic haemodialysis 41.29% anti-HCV antibody prevalence was found. The prevalence of anti-HBc and anti-HCV antibodies in correlation with the number of transfusions was examined as well, in serums of chronic uraemic patients. Anti HBc antibody prevalence was significantly higher in the polytransfused group (p less than 0.01), compared to the group without transfusion. There were no correlation between the number of transfusions and anti-HCV antibody occurrence. ALT values were in correlation with HBV and HCV seropositives. Elevated ALT levels were found in patients with HBV and/or HCV infection. In conclusion, screening for HBV and HCV markers among patients receiving blood, blood donors and medical staff workers seems to be necessary in the future. The results suggest the determination of anti-HBc to be an early and common marker of hepatitis B and C and the frequent occurrence of nosocomial transmission and the importance of prevention at high risk patients. PMID- 1630803 TI - [Viral hepatitis and morphology of hepatitis viruses]. AB - Our knowledge has increased significantly about the hepatitis viruses and the disease caused by them. The most important hepatitis inducing viruses are the hepatitis A, B, C, D and E viruses, however, probably new members will be added soon. The possibility of differentiation and detection of these viruses was based on methods of molecular biology and serology. PMID- 1630804 TI - [Clinical significance of the hepatitis Delta virus and its incidence in virus B positive chronic liver diseases]. AB - The data on hepatitis delta virus and the liver diseases caused by it are reviewed. The findings of hepatitis B and D virus markers in 118 hepatitis B virus seropositive patients suffering from histologically confirmed chronic liver disease are reported. The prevalence of hepatitis delta virus infection was 13.56% of these cases, while active hepatitis delta virus replication was proved in 6 cases of them. Based on their findings, the role of hepatitis delta virus in the progression of chronic liver diseases is concluded, similarly to data published earlier. The importance of repeated, detailed virus-serological and histological examinations is stressed, especially in the cases in which the progression of liver disease are detected. The authors suggest that HBsAg--IgM complex seropositivity in patients suffering from anti-delta seropositive chronic liver disease supports active hepatitis delta virus infection. PMID- 1630805 TI - [Chronic hepatitis treated with alpha-interferon]. AB - The newest results on the interferon treatment of chronic viral hepatitis on the ground of controlled trials are reported. In chronic type B hepatitis about 35 percent of patients, while in chronic type C hepatitis 80 percent of patients showed good response, though in the latter disease relapse is frequent following the stop of interferon treatment. In hepatitis Delta infection further therapeutic studies are warranted. The duration of the interferon treatment in chronic viral hepatitis is still an unsolved question. PMID- 1630807 TI - [Recommendations for the diagnosis and treatment of viral hepatitis based on the results of the Viral Hepatitis Symposium 1991]. PMID- 1630806 TI - [Treatment of chronic viral hepatitis with recombinant interferon-alfa]. AB - The antiviral treatment with alfa-interferon is the first proven therapeutic possibility in chronic viral hepatitis. The rate of improvement to alfa interferon ranges between 15-40% depending on the type of hepatitis. The optimal dose is 5 MU/day three times a week for 6 months in chronic hepatitis B, while 3 MU/day three times a week for months in chronic hepatitis C. Results of therapy can be improved using combination treatment in selected cases. PMID- 1630808 TI - [Significance of detailed Hepatitis B virus marker studies in chronic liver diseases]. AB - The hepatitis B virus (HBV) markers were studied by Sorin RIA kits in the sera of 390 patients suffered from histologically confirmed chronic liver disease. On the base of HBsAg, anti-HBs, anti-HBc seronegativity the HBV infection was excluded in 235 cases. In most HBV negative cases the diagnosis was fatty liver and alcoholic hepatitis (52%), while chronic active hepatitis and/or liver cirrhosis occurred only in 21.7% of patients. Past or present HBV infection was proved in 155 patients. The diagnosis of 52.9% of cases in this group was chronic active hepatitis and/or liver cirrhosis, while fatty liver and alcoholic hepatitis occurred in 27.7%. The detailed HBV marker analysis was performed in 76 patients. Previous infection without replication (anti-HBs and/or anti-HBc and/or anti-HBe positivity) was proved in 48 cases, 12 patients have active HBV infection (HBsAg, HBe, IgM anti--HBc, positivity), while in 16 cases integrated HBV infection (HBsAg, anti-HBc, anti-HBe positivity) was proved. The HBsAg--IgM complex seropositivity was detected in every case with active HBV replication. Because of therapeutic, prognostic and epidemiologic significances the detailed HBV serology in chronic liver diseases is stressed. PMID- 1630810 TI - tek, a novel tyrosine kinase gene located on mouse chromosome 4, is expressed in endothelial cells and their presumptive precursors. AB - A search for protein tyrosine kinases expressed during murine cardiogenesis resulted in the isolation of a novel tyrosine kinase, designated tek, which maps to mouse chromosome 4 between the brown and pmv-23 loci. The deduced amino acid sequence of tek predicts that it encodes a putative receptor tyrosine kinase that contains a 21 amino acid kinase insert and which is most closely related in its catalytic domains to FGFR1 and the product of the ret proto-oncogene. In situ hybridization analysis of adult tissues, as well as sectioned and whole-mount embryos, showed that tek is specifically expressed in the endocardium, the leptomeninges and the endothelial lining of the vasculature from the earliest stages of their development. Moreover, examination of the morphology of tek expressing cells, and staging of tek expression relative to that of the endothelial cell marker von Willebrand factor, revealed that tek is expressed prior to von Willebrand factor and appears to mark the embryonic progenitors of mature endothelial cells. tek encodes a novel putative receptor tyrosine kinase that may be critically involved in the determination and/or maintenance of cells of the endothelial lineage. PMID- 1630809 TI - A high proportion of early response genes are constitutively activated in T cells by HTLV-I. AB - Immortalization of T cells by HTLV-I is mediated by the X region of the virus and probably involves transactivation of cellular genes. We show that T cells transformed by HTLV-I constitutively express a high proportion of early response genes that are normally transiently induced following antigenic or mitogenic activation of T cells. Thus, HTLV-I-infected T cells display an 'early activation' phenotype that is distinct from the gene expression pattern of continuously dividing T cells. Ten early response genes representing a diverse array of functional categories were assayed. Four DNA-binding proteins/transcription factors including the p50 subunit of NF-kappa B were evaluated. A protein(s) encoded by the X region of HTLV-I appeared to contribute to up-regulated expression of most, if not all, of the early response genes. For those genes that could be assayed, increased transcriptional rates, but not substantial changes in mRNA half-life, were demonstrated in the presence of pX encoded proteins, suggesting that the transcriptional transactivator, Tax, affects the induction or maintenance of transcription for these mitogen-inducible genes. Therefore, Tax may mimic or interact with a component(s) of the signal transduction pathway activated by antigen or mitogen treatment. These data demonstrate that early response genes, some of which probably play roles in initiating or maintaining cellular proliferation, are frequent targets of HTLV-I activation. PMID- 1630811 TI - c-Ha-ras gene mutation and activation precede pathological changes in DMBA induced in vivo carcinogenesis. AB - We have previously reported a stage-specific and sequential overexpression of the c-Ha-ras and c-erbB genes in 7, 12-dimethylbenzanthracene (DMBA)-induced in vivo carcinogenesis in hamster buccal pouch epithelium (HBPE). In this investigation, the immunoreactive protein product of the c-Ha-ras gene (p21 protein) was identified in HBPE cells, specifically in treated tissues and cultured cells established after 3 weeks of DMBA treatment. Microscopic examination did not show any histopathological changes in these tissues. The p21 protein was detected in a few selective cells, which were dispersed away from the more densely populated basal layer. The overexpression of the c-Ha-ras gene was accompanied by a point mutation of A----T in codon 61 (CAA), inducing an amino acid substitution from the wild-type glutamine to leucine in the peptide. The concurrent molecular modifications preceded any detectable histopathological changes. The cellular morphology and orientation in treated HBPE at this early stage was indistinguishable from the control tissue. Yet the genetic alterations, such as the point mutation and overexpression of the gene, were evident at the predysplastic stage. Amplification and overexpression of the second proto oncogene, c-erbB, and its product, epidermal growth factor receptor (EGFR), were detected in HBPE cells at the later stages of extensive cell proliferation and invasion. By using double antibodies and two immunoreporter systems, we demonstrated overexpression of both c-Ha-ras and c-erbB genes in the same HBPE cells during this chemically induced in vivo carcinogenesis. PMID- 1630812 TI - Establishment and characterization of a malignant melanocytic tumor cell line expressing the ret oncogene. AB - We established a cell line (designated Mel-ret) from a melanocytic tumor developed in a metallothionein/ret transgenic mouse. Unlike primary melanocytic tumors, which did not show malignant features, when the Mel-ret cells were transplanted into nude mice they invaded into surrounding tissues and had metastatic ability. Although the Ret proteins were expressed at similar levels in the cell line and the primary tumors, the level of tyrosine phosphorylation in the Mel-ret cells was much higher than that in the primary tumors. In particular, an 85-kDa tyrosine-phosphorylated band was specifically detected in the Mel-ret cells. These results suggest that the increase in tyrosine phosphorylation may be responsible for malignant transformation of the Mel-ret cells. Immunofluorescence and cell fractionation studies showed that the Ret proteins and most of tyrosine phosphorylated proteins in the Mel-ret cells localized in the membrane fraction. No activation of phosphatidyl-inositol-3 kinase (PI-3 kinase), a target protein for several tyrosine kinases, was detected in the Mel-ret cells. PMID- 1630813 TI - A novel sequence in the type IV collagen promoter binds nuclear proteins from Engelbreth-Holm-Swarm tumor. AB - The production of extracellular matrix proteins is an important element of tumor formation, and alterations in matrix protein metabolism may be critical to the process of tumor metastasis. Abundant expression of type IV collagen, the major structural protein of the basement membrane, is characteristic of the Engelbreth Holm-Swarm (EHS) mouse sarcoma. In the present study, we evaluated mechanisms of transcriptional regulation of type IV collagen genes by analysing nuclear factors that bind to the promoter region. Gel mobility-shift assays indicated that specific proteins from EHS tumor bound the promoter and generated several unique shift patterns. The specific sequences to which these proteins bound were determined using DNAase I protection assays. DNA-binding proteins protected two regions from DNAase I digestion. The first region was similar to a GC box, the binding site for the transcription factor Sp1. The other footprint was a 30-bp region that contained the novel sequence motif, 'CCCTCCC' present in several other extracellular matrix promoters. Nuclear extracts isolated from tissues that variably express type IV collagen bound to this protected sequence with distinctly different shift patterns. Furthermore, in highly expressing tissues, unlabeled oligonucleotides containing the 'CCCTCCC' motif effectively inhibited nuclear protein binding with the entire promoter. Thus, it is likely that a novel protein or protein complex binds to these sequences. Furthermore, these sequences appear to be unique to the genes that encode basement membrane proteins, suggesting a specific role in their regulation. PMID- 1630814 TI - Human pancreatic carcinomas and cell lines reveal frequent and multiple alterations in the p53 and Rb-1 tumor-suppressor genes. AB - The molecular pathology of human pancreatic cancer is poorly understood, particularly with regard to the role of known tumor-suppressor genes. We have examined the expression of the p53 and Rb-1 tumor-suppressor genes in seven human pancreatic carcinoma cell lines and 10 primary pancreatic carcinomas. Examination of the Rb-1 gene by Northern hybridization and immunoprecipitation analyses revealed the absence of Rb-1 protein expression in two cell lines. Moreover, regions of absent nuclear staining in two primary pancreatic carcinomas were detected by immunohistochemical analysis. Investigation of p53 by Southern, Northern, immunohistochemical and immunoprecipitation analyses revealed multiple abnormalities, including gross rearrangements in two cell lines, the absence of detectable p53 transcript in two cell lines and a truncated transcript in one line. Six cell lines overexpressed p53 protein, while one line revealed the absence of p53 product by immunohistochemical and immunoprecipitation analyses. Sequence analysis of exons 5-8 of the p53 gene confirmed these analyses, revealing missense mutations in all seven cell lines in codons 181, 220, 248, 249, 265, 272 and 273. Of 10 mutations identified, nine were transitions and 50% were in codon 273. Immunohistochemical analyses of frozen primary pancreatic carcinomas revealed positive nuclear staining for p53 in 40% of cases. Mutations were identified in codons 238 and 286 and in intron 9 in several representative specimens. Alterations in the p53 and Rb-1 genes may be important features in the development of human pancreatic cancer. PMID- 1630815 TI - The HIV tat gene transforms human keratinocytes. AB - Skin disorders are frequently seen in patients with the acquired immune deficiency syndrome (AIDS). Since many of these cutaneous manifestations are accompanied by an early onset of epidermal hyperplasia, the keratinocyte is a candidate for infection by the human immunodeficiency virus (HIV). We now report that the HIV tat gene, under the control of the viral long terminal repeat (LTR), can efficiently transform human keratinocytes in culture. Our finding suggests that this activity of the tat gene may be responsible for the epidermal hyperplasia that accompanies psoriasis and precedes the development of squamous cell and basal cell carcinomas in AIDS patients. PMID- 1630816 TI - v-Myc, but not Max, possesses domains that function in both transcription activation and cellular transformation. AB - Deregulated expression of myc gene family members is associated with the development of malignant neoplasms in several species. Despite the evidence linking expression of this family of nuclear proteins with the proper control of cellular growth and development, the function of the myc protein remains unknown. Intrigued by the observed structural similarity between the myc protein and several eukaryotic transcription factors, we have investigated the ability of the MC29 viral myc protein to activate transcription of a heterologous promoter in C3H10T1/2 cells. Overlapping portions of v-myc coding sequences were inserted 3' to the yeast GAL4 DNA-binding domain and tested for their ability to activate transcription of a chloramphenicol acetyl transferase reporter gene containing GAL4 binding sites. Two transcription activation domains were identified within the amino terminus of v-Myc. The importance of these regions for cellular transformation was examined using ras/myc co-transformation assays. Our results demonstrate that deletion of either of the transcription activation domains, or the DNA-binding and protein oligomerization domains, abolishes the ability of v Myc to cooperate with Ras to transform C3H10T1/2 cells. Similarly, we investigated whether Max, the protein-binding partner of Myc, also possesses the potential to activate transcription. Interestingly, chimeric GAL4/Max proteins were not functional in our assays, suggesting that the potential of the Myc-Max complex to influence gene expression and function in cellular transformation relies primarily on sequences found within the amino terminus of Myc. PMID- 1630817 TI - Loss of transforming growth factor beta 1 (TGF-beta 1)-induced growth arrest and p34cdc2 regulation in ras-transfected epithelial cells. AB - Transforming growth factor beta 1 (TGF-beta 1) is a potent inhibitor of mink lung epithelial (CCL64) cell growth in culture. The fact that many transformed epithelial cells have escaped from negative growth control by TGF-beta 1 suggests that transfected epithelial cells may be an appropriate model for investigating the growth-inhibitory mechanism of TGF-beta 1. We transfected CCL64 cells with a mouse c-myc oncogene (pSVc-myc1), a mutated Harvey-ras (Ha-ras) oncogene, or a combination of both. The results indicate that cells transfected with c-myc alone exhibit normal morphology and maintain sensitivity to TGF-beta 1 growth arrest, but are unable to form colonies in soft agar in the presence or absence of TGF beta 1. Cells transfected with Ha-ras, or co-transfected with c-myc, display a transformed morphology, grow spontaneously under anchorage-independent conditions and acquire a complete resistance to growth inhibition by TGF-beta 1. Affinity cross-linking of [125I]TGF-beta 1 to cell-surface receptors from these transfectants revealed that all three TGF-beta receptor types were present and no significant differences in [125I]TGF-beta 1 labeling of these receptors was observed. Since we have previously demonstrated that modulation of p34cdc2 kinase is a marker for TGF-beta 1 growth inhibition, we investigated p34cdc2 activity in the CCL64 transfected clones. The results show that in the control CCL64 cells and in the myc-transfected clones TGF-beta 1 regulation of p34cdc2 activity is maintained. In the ras- and ras + myc-transfected cells p34cdc2 phosphorylation and histone H1 kinase activity is significantly increased and regulation by TGF beta 1 is lost. PMID- 1630819 TI - Mechanism of estrogen activation of c-myc oncogene expression. AB - The estrogen receptor complex is a known trans-acting factor that regulates transcription of specific genes through an interaction with a specific estrogen responsive cis-acting element (ERE). In previous studies we have shown that in estrogen-responsive human breast cancer cells estrogen rapidly activates c-myc expression. This activated expression occurs through enhanced transcription and does not require the synthesis of new protein intermediates; therefore, an ERE is present in the human c-myc gene regulatory region. To localize the ERE, constructs containing varying lengths of the c-myc 5'-flanking region ranging from -2327 to +25 (relative to the P1 promoter) placed adjacent to the chloramphenicol acetyl transferase reporter gene (CAT) were prepared. They were used in transient transfection studies in MCF-7 and HeLa cells co-transfected with an estrogen receptor expression vector. These studies reveal that all constructs containing the P2 promoter region exhibited estrogen-regulated CAT expression and that a 116-bp region upstream and encompassing the P2 TATA box is necessary for this activity. Analysis of this 116-bp region failed to identify a cis-acting element with sequences resembling the consensus ERE; however, co transfection studies with mutant estrogen receptor expression vectors showed that the DNA-binding domain of the receptor is essential for estrogen-regulated CAT gene expression. We have also observed that anti-estrogen receptor complexes can weakly trans-activate from this 116-bp region but fail to do so from the ERE containing ApoVLDLII-CAT construct. To explain these results we propose a new mechanism of estrogen trans-activation in the c-myc gene promoter. PMID- 1630818 TI - Phosphorylation and regulatory effects of the carboxy terminus of a Drosophila src homolog. AB - The kinase activities of the vertebrate src family members are repressed by phosphorylation of a tyrosine residue in the carboxy-terminal 'tail' of these molecules. To explore whether the tail of an invertebrate src homolog might also serve a regulatory function, we examined the ability of the carboxy terminus of a Drosophila src homolog (p62D), which contains a tyrosine homologous to those in the vertebrate src family members, to regulate the following molecules in mammalian fibroblasts: (1) a chimeric protein, p60CD, containing the amino terminus and catalytic domains of chicken p60c-src joined to the C-terminus of p62D; and (2) full-length p62D itself. By a variety of criteria p60CD appears to be a partially, rather than fully, repressed form of p60c-src. Phosphopeptide mapping indicates that partial repression correlates with partial phosphorylation of the tyrosine in the p62D tail of the chimera. Phosphorylation of the tail may also regulate full-length p62D. Expression of p62D in fibroblasts does not affect cell morphology or the overall abundance of tyrosine-phosphorylated proteins. The molecule is phosphorylated at its C-terminal tyrosine (Tyr-547), but not at its in vitro autophosphorylation sites, suggesting that it is catalytically repressed in fibroblasts. Expression of a truncated p62D mutant lacking Tyr-547 is associated with a clear alteration in cellular morphology and a two- to threefold increase in cellular phosphotyrosine levels. These results suggest that phosphorylation of the C-terminal tyrosine of the tail of an invertebrate src like kinase can repress the activity of adjacent catalytic domains. PMID- 1630820 TI - Isolation of chromosome-specific DNA sequences from an Alu polymerase chain reaction library to define the breakpoint in a patient with a constitutional translocation t(1;13) (q22;q12) and ganglioneuroblastoma. AB - We describe the cytogenetic and molecular characterization of a t(1;13)(q22;q12) constitutional rearrangement occurring in a patient with a relatively benign form of neuroblastoma, called ganglioneuroblastoma. Somatic cell hybrids were generated between mouse 3T3 cells and a lymphoblastoid cell line from this patient, D.G. One isolated subclone, DGF27C11, contained the derivative chromosome, 1pter-q22::13q12-qter, but no other material from either chromosome 1 or 13. Using available DNA probes the 13 breakpoint was assigned proximal to all reported markers. In order to generate flanking markers to define this translocation further, an Alu polymerase chain reaction library was constructed from a somatic cell hybrid containing only the proximal, 13pter-13q14, region of chromosome 13. Seven unique sequences have been isolated from the library, three of which lie below and four of which lie above the 13q12 breakpoint. More precise mapping of the distal markers was achieved using a panel of somatic cell hybrids with overlapping deletions of chromosome 13. The paucity of probes in the 1q22 region has made a precise assignment of this breakpoint difficult, however it has been shown to lie distal to c-SKI and proximal to APOA2. This refined characterization of the breakpoint is a prerequisite for its cloning, which may yield genes important in the pathogenesis of ganglioneuroblastoma. PMID- 1630821 TI - Large-scale molecular mapping of human c-myb locus: c-myb proto-oncogene is not involved in 6q- abnormalities of lymphoid tumors. AB - Chromosomal abnormalities in the 6q region have been observed frequently in several T-cell and myeloid leukemias. Interestingly, this region was found to contain three cellular oncogenes, c-myb, c-fyn and c-ros. Several of the tumors that exhibit 6q- abnormalities have also been found to express high levels of c myb and, in some cases, amplification of the c-myb gene, leading to the suggestion that this gene could lie in proximity to the deletions observed in these tumors. To determine if c-myb gene activation is associated with 6q- abnormalities, we developed a megabase map of the human c-myb locus using pulsed field gel electrophoresis. We then examined the occurrence of abnormalities near the c-myb gene in several hematopoietic tumor cell lines containing well characterized 6q- abnormalities. Our results show that no rearrangements or deletions occur within a region of 1.0 Mbp of the c-myb locus in these cell lines. However, several of the cell lines exhibited differential and partial methylation patterns which seem to be prevalent amongst different cell lines. PMID- 1630822 TI - Deletion mapping of chromosome 3p in female genital tract malignancies using microsatellite polymorphisms. AB - We have constructed deletion maps of chromosome 3p for cancers of the female genital tract (uterine endometrium, uterine cervix and ovary). The tumours were tested for loss of heterozygosity using CA-repeat polymorphisms. The high degree of informativeness of these markers allowed the construction of detailed deletion maps from a relatively small number of samples. A common region of deletion was identified at chromosome 3p13-21.1 in endometrial cancer and at 3p13-14.3 in cervical cancer; 5 out of 13 (38%) endometrial cancers and six out of eight (75%) cervical cancers showed loss of heterozygosity at these regions. In ovarian cancer a separate common region of deletion was identified at 3p21.1-22; two out of four (50%) ovarian cancers had alleles deleted at this region. These data suggest the presence of a tumour-suppressor gene(s) for endometrial and cervical cancer at 3p13-21.3 and a separate gene at 3p21.1-22 that is involved in the carcinogenesis of ovarian cancer. PMID- 1630823 TI - Human wild-type p53 adopts a unique conformational and phosphorylation state in vivo during growth arrest of glioblastoma cells. AB - The wild-type (wt) human tumor-suppressor gene product, p53, and its mutant form have been analysed in an in vivo system in which the inducible expression of wt p53 results in growth arrest in the G1 phase of the cell cycle. Two major pools of p53 are detected after wt p53 expression by their differential reactivity with the p53 monoclonal antibodies PAb 421 and 1801 as well as the mutant and wt specific monoclonal antibodies PAb 240 and 1620; one pool contains wt and mutant p53 and is characterized as having a mutant conformation, whereas the other pool contains only wt p53 with a wt conformation. As G1 arrest is entered, the amount of wt p53 associated with the mutant pool decreases, such that by 12 h free wt and mutant p53 are the major pools. Two-dimensional gel analysis of the p53 pools revealed that free wt p53 is phosphorylated to a greater degree than mutant p53, which correlated with the loss of the PAb 421 epitope on wt p53. In summary, the ability of wt p53 to exert an antiproliferative effect correlates with the presence of a unique conformational state of wt p53 characterized by increased phosphorylation and the loss of both the PAb 421 epitope and association with mutant p53 pool, whereas mutant p53 is unable to assume this conformational state. PMID- 1630824 TI - Altered conformation of the p53 protein in myeloid leukemia cells and mitogen stimulated normal blood cells. AB - Expression of the normal p53 gene promotes cell differentiation, maturation and apoptosis. The mutant p53 gene, which does not function normally, is frequently expressed at elevated levels in tumor cells [for review see Lane, D.P. & Benchimol, S. (1990). Genes Dev., 4, 1-8]. We have analysed the expression of and mutational change in the p53 gene in the peripheral blood cells of 49 primary acute myeloid leukemia (AML) patients. The p53 protein levels were elevated in 37 patients (75%) when measured by immunoprecipitation with antibodies PAb1801 and PAb421, which recognize both normal and mutant forms of the protein. The p53 protein from 32 of these 37 patients was immunoprecipitated by PAb240, which recognizes a conformation of p53 protein associated with point mutations. However, point mutations were detected by single-stranded conformation polymorphism (SSCP) assay and direct sequencing in only three patients at codons 178, 245, 273 and 290. Growth stimulation of normal lymphocytes also generated p53 which was immunoprecipitable by PAb240. Thus, alteration of p53 conformation, rather than acquisition of point mutations, could be the mechanism underlying the increased proliferation of myeloid cells in most AML patients. PMID- 1630825 TI - The conformational change of a murine temperature-sensitive p53 protein is independent of a change in phosphorylation status. AB - Wild-type and mutant p53 proteins exhibit opposing activities in respectively suppressing and promoting tumour development. In a rat embryo fibroblast cell line transformed with a murine temperature-sensitive p53 gene, p53 functions as a oncogene at 37 degrees C and as a tumour suppressor at 32 degrees C [Michalovitz, D., Halevy, O. & Oren, M. (1990). Cell, 62, 671-680]. We have used this cell line to investigate whether this temperature-dependent switching of function involves changes in the phosphorylation of p53 protein. Monoclonal antibodies PAb246 and PAb240 were used to immunoprecipitate metabolically 32P-labelled p53 protein in the 'wild-type' or mutant conformation from cells grown at 32 degrees C or 37 degrees C. Tryptic phosphopeptide maps were prepared from the isolated 'wild type' and mutant p53 proteins. At 32 degrees C and 37 degrees C phosphopeptide maps of the 'wild-type' and mutant protein were identical. This demonstrates that the temperature-dependent conformation change, and associated functional change, in the p53 protein does not involve a change in the state of phosphorylation. PMID- 1630826 TI - Chromosomal assignment of two human B-raf(Rmil) proto-oncogene loci: B-raf-1 encoding the p94Braf/Rmil and B-raf-2, a processed pseudogene. AB - The B-raf gene is the human homolog of the avian c-Rmil proto-oncogene encoding a 94-kDa serine/threonine kinase detected in avian cells. We have previously shown that this protein contains amino-terminal sequences not found in other proteins of the mil/raf gene family. These sequences are encoded by three exons in the avian genome. We report that these three exons are conserved in the human B-raf gene and that they encode an amino acid sequence similar to that of the avian c Rmil gene, indicating that in both avian and mammalian species the product of the B-raf/c-Rmil gene is a 94-kDa protein. We also identified two human B-raf loci: B raf-1, located on chromosome 7q34, which encodes the functional B-raf/Rmil gene product, and B-raf-2, an inactive processed pseudogene located on chromosome Xq13. PMID- 1630828 TI - Acoustic neuroma I. Surgical management. PMID- 1630827 TI - Tumorigenic effects mediated in the avian embryo by one or more oncogenes associated with v-myc. AB - We have previously shown that introduction of the v-myc oncogene in chick or quail embryos at E3 induces rapidly growing heart rhabdomyomas. We now report that a retrovirus containing one or two other oncogenes induces additional pathologies specified by the v-myc-associated oncogene. The v-mil/myc combination introduced at E3 induces, in addition to heart rhabdomyomas, tumors of proliferating cells aggregated onto the luminal aspect of vessels in both chick and quail embryos. In the quail these cells react positively with the quail specific mAb QH1, which recognizes endothelial and most hemopoietic cells, while chick intravascular cells do not react with the chick-specific mAb VIA2 that recognizes hemopoietic cells. Thus the v-mil/myc tumors appear to be of endothelial origin. The v-myb-ets/myc combination injected at E3 induces cardiorhabdomyomas and aggressive VIA2-positive hemopoietic tumors in chick embryos, but only the v-myc-induced cardiorhabdomyomas in quail embryos. When injected into hatched animals, v-myc alone transforms hemopoietic and perhaps endothelial cells, but not cardiac cells. Thus the developmental stage at which a cell type can be transformed by v-myc and another associated oncogene depends on as yet undefined species-specific factors. More importantly, several examples of oncogene cooperation in vivo are adduced by these experiments. The type of cell transformed is specified by the viral oncogene combination. PMID- 1630829 TI - Microsurgical anatomy of acoustic neuroma. AB - Because acoustic neuromas most frequently arise in the posteriorly placed vestibular nerves, they usually displace the facial and cochlear nerves anteriorly (Figs. 11, 12, and 13). The facial nerve is stretched around the anterior half of the tumor capsule. Variability in the direction of growth of the tumor arising from the vestibular nerves may result in the facial nerve being displaced, not only directly anteriorly, but also anterior-superiorly or anterior inferiorly. The nerve is infrequently found on the posterior surface of the tumor. Because the facial nerve always enters the facial canal at the anterior superior quadrant of the lateral margin of the meatus, it is usually easiest to locate it here, rather than at a more medial location where the degree of displacement of the nerve is more variable. The cochlear nerve also lies anterior to the vestibular nerve and is most frequently stretched around the anterior half of the tumor. The strokes of the fine dissecting instruments used in removing the tumor should be directed along the vestibulocochlear nerve from medial to lateral rather than from lateral to medial because traction medially may tear the tiny filaments of the cochlear nerve at the site where these filaments penetrate the lateral end of the meatus to enter the cochlea. The landmarks that are helpful in identifying the facial and vestibulocochlear nerves at the brain stem on the medial side of the tumor have been reviewed. These nerves, although distorted by tumor, can usually be identified on the brain stem side of the tumor at the lateral end of the pontomedullary sulcus, just rostral to the glossopharyngeal nerve and just anterior-superior to the foramen of Luschka, flocculus, and choroid plexus protruding from the foramen of Luschka. After the facial and vestibulocochlear nerves are identified on the medial and lateral sides of the tumor, the final remnants of the tumor are separated from the intervening segment of the nerves. In the three approaches to the meatus and cerebellopontine angle- retrosigmoid, translabyrinthine, and middle fossa--a communication may be established between the subarachnoid space and the mastoid air cells that requires careful closure to prevent a cerebrospinal fluid leak. PMID- 1630830 TI - Retrosigmoid approach for acoustic tumor removal. AB - The retrosigmoid technique has evolved from the traditional suboccipital operation and, when combined with removal of the posterior wall of the internal auditory canal, affords a wide exposure of the cerebellopontine angle. This approach may be used for acoustic neuromas of all sizes, from intracanalicular to more than 4 cm from the porus acusticus. Hearing preservation may be attempted and is generally successful in a substantial minority of cases. The facial nerve is readily visualized at the lateral end of the internal auditory canal and is at no greater risk than in the translabyrinthine operation. We use this approach for all hearing preservation surgery as well as for tumors of more than 3 cm, regardless of hearing. PMID- 1630831 TI - Translabyrinthine approach for acoustic tumor removal. AB - The translabyrinthine approach is the most direct route to the cerebellopontine angle. It is the preferred approach for removal of all tumors in patients with poor hearing and for large tumors when the likelihood of hearing preservation is slight. This approach offers the advantages of minimum cerebellar retraction, identification of the facial nerve proximally and medially, and the ability to repair immediately the facial nerve if it is severed during acoustic tumor removal. This approach has the lowest morbidity with regard to spinal fluid leaks and also postoperative headaches. PMID- 1630832 TI - Transotic approach to the cerebellopontine angle. AB - The transotic approach to the cerebellopontine angle for resection of tumors invading the internal auditory canal provides superior illumination and exposure for optimal preservation of facial nerve function. Separation of facial nerve from tumor is enhanced with an anterior exposure that allows visualization of the intracranial segment of the nerve before tumor removal without significantly increasing total operative time. Facial nerve grafting or hypoglossal-facial anastomosis may be incorporated into the procedure at the time of tumor resection using the transotic approach. When combined with a musculofascial patch secured to the dural defect, the initial subtotal petrosectomy with eustachian tube and middle ear cleft obliteration generally avoids the complication of an immediate or delayed postoperative cerebrospinal fluid leak. The transotic approach is indicated for tumors up to 2.5 cm in size that are not adherent to the brain stem. PMID- 1630833 TI - Middle fossa approach for acoustic tumor removal. AB - The middle fossa approach is well suited for the removal of small acoustic tumors with possible hearing preservation. The most appropriate candidates have tumors with less than 5 mm extension into the cerebellopontine angle and good preoperative hearing (speech reception threshold less than or equal to 30 dB, speech discrimination score greater than or equal to 70%). Measurable postoperative hearing can be preserved in 31% to 59% of patients, and normal or near normal facial function occurs in 86% to 89%. Serious postoperative complications are rare with this approach. With the advent of gadolinium-enhanced MRI, it is now possible to diagnose acoustic tumors reliably when small and before hearing has been significantly affected. The middle fossa approach provides excellent access for the removal of these small tumors. PMID- 1630834 TI - Selection of surgical approach to acoustic neuroma. AB - A variety of surgical approaches are available in the management of acoustic neuroma. Each procedure has certain advantages and disadvantages in terms of surgical exposure, the capability of preserving cranial nerve function, and postoperative morbidity. This article advocates tailoring the operative approach to each acoustic neuroma according to its size, location, and clinical manifestations. PMID- 1630835 TI - Complications in acoustic neuroma surgery. AB - There has been a continuous lowering of mortality and morbidity rates in the 20th century, thanks to increasing experience and newer technology. Despite this, the readership should be aware of the hazards involved in this challenging field. Complications occur, and their incidence, mechanism, management, and prevention have been outlined here so physicians performing these procedures will be better prepared to manage them. We have found that the occurrence of complications can be greatly reduced through a team approach using the combined talents of a neurotologist, neurosurgeon, and frequently an internist. It is apparent from this article that the morbidity of removing larger tumors is significantly greater than the morbidity of removing small tumors. The recent introduction of MRI to the diagnostic armamentarium of the neurotologist may permit earlier detection and a further reduction of morbidity and mortality rates. Only continued study of prevention of complications will assure the improved quality of our results for patients undergoing microsurgical removal of acoustic neuromas. PMID- 1630836 TI - Intraoperative monitoring of facial and cochlear nerves during acoustic neuroma surgery. AB - The likelihood of successful preservation of facial and cochlear nerve function during acoustic neuroma surgery has been improved by the advent of intraoperative monitoring techniques. The facial nerve is monitored by recording EMG from facial muscles, with no muscle relaxants used; mechanical irritation of the nerve during surgery causes increased EMG activity, which can be detected in real time using a loudspeaker. Brief episodes of activity associated with specific surgical maneuvers aid the surgeon in avoiding damage to the nerve, whereas prolonged tonic EMG activity may reflect significant neural injury. Electrical stimulation with a hand-held probe elicits evoked EMG responses, which can be used to locate and map the nerve in relation to the tumor. The threshold for eliciting evoked EMG responses provides a rough indicator of the functional status of the nerve. Different nerves in the posterior fossa (trigeminal, facial, spinal accessory) can be identified in multichannel recordings by the spatial distribution and latency of responses to electrical stimulation. The ability to elicit EMG responses from low amplitude stimulation of the facial nerve at the brain stem after tumor removal is a reasonable predictor of postoperative facial function. Cochlear nerve function is assessed by recording the ABR from ear canal and scalp electrodes or the CNAP with an electrode placed directly on the nerve at the brain stem root entry zone. The ABR is a well-known, noninvasive technique that can be adapted to intraoperative use relatively easily but is of limited utility owing to the delay inherent in signal averaging. Direct CNAP recordings require placement of an intracranial electrode in such a way as to contact the cochlear nerve without interfering with surgical access but have the distinct advantage of rapid feedback on changes in cochlear nerve status. PMID- 1630837 TI - Management of bilateral acoustic neuroma. AB - This article has reviewed the genetic disorder, neurofibromatosis 2. The history, nomenclature, genetic etiology, epidemiology, diagnostic criteria, pathogenesis, and presentation of neurofibromatosis 2 have been given. A related but distinctly different disorder, neurofibromatosis 1, has also been described. The diagnostic evaluation of neurofibromatosis 2 has been discussed with an emphasis on the importance of early diagnosis. An analysis of the surgical treatment of bilateral acoustic neuromas as well as nonsurgical therapeutic alternatives has been presented. The results and complications in the operative management of 86 acoustic tumors in 49 patients with neurofibromatosis 2 have been described in detail. The poor immediate hearing results and the even poorer long-term hearing results have been examined in light of the invasive histopathology of these tumors. It has been emphasized that patients with neurofibromatosis 2 and asymptomatic family members require comprehensive, multidisciplined, long-term management. PMID- 1630838 TI - Stereotactic radiosurgery in the treatment of patients with acoustic tumors. AB - Stereotactic radiosurgery is performed under local anesthesia, and most patients can be discharged from the hospital within 24 hours of treatment. All patients in our series returned to their preoperative level of employment or function within 5 to 7 days of treatment, and this functional level was maintained over the period of follow-up. "Tumor control" was achieved in 96% of patients during an average follow-up of 1.7 years. Tumor shrinkage occurred in 45% of patients who had at least 1.5 years of follow-up. Useful hearing preservation rates were 50% at 6 months and 30% 1 year after treatment. New delayed facial or trigeminal neuropathy occurred in 34% and 32% of patients, respectively, with a median onset of 5 to 6 months after treatment. The vast majority of cranial neuropathies were partial at onset and tended to improve over time. Other complications included tumor growth (4%), communicating hydrocephalus (4%), and transient adjacent brain parenchymal changes best seen on T2-weighted MRI (9%). Stereotactic radiosurgery is an important alternative treatment for carefully selected patients with acoustic tumors. Indications for treatment include sufficient medical problems to pose excessive surgical risk, advanced age, the presence of bilateral acoustic tumors or contralateral deafness, recurrent tumor despite surgical resection, or refusal to undergo microsurgery. Radiosurgery is contraindicated in patients with symptomatic brain stem or cerebellar compression from a large acoustic tumor. Previous posterior fossa radiotherapy is a relative contraindication that must be considered on a patient to patient basis. Stereotactic radiosurgery should be viewed as an additional weapon in our arsenal for combating acoustic tumors rather than feared as a potential replacement for surgical excision. The strategic role of stereotactic radiosurgery in the overall treatment of patients with acoustic tumors will continue to be refined as longer-term, carefully assessed results become available. PMID- 1630839 TI - Bladder pressure and kidney function in children with myelomeningocoele: review article. AB - Therapy of children with myelomeningocoele should achieve a double goal: on the one hand, obtain continence and, on the other hand, preserve kidney function without complications. The first goal is a social and psychological one, the latter is a vital one. PMID- 1630840 TI - Hangman's fracture in Singapore (1975-1988). AB - A retrospective study of 33 patients with fracture of the ring of the axis (hangman's fracture) admitted to the Spinal Unit of the Department of Rehabilitation Medicine in the Tan Tock Seng Hospital between 1975 and 1988 was carried out. The aims were to establish the causes, mechanism and outcome of injuries that lead to Hangman's fracture in Singapore. The majority were males (27) and their ages ranged from 16 to 82 with a mean age of 33.7 years. 63.6% (21 cases) were due to road traffic accidents of whom 33% (11 cases) were motorcyclists or pillion riders and 30.3% (10 cases) were drivers or passengers of four wheel vehicles such as cars and vans. Using Effendi et al's classification, we have 21 type I, 11 type II and one type III fractures. Thirteen type I, 6 type II and one type III cases had no neurological deficit on admission. The rest had deficits ranging from tetraparesis to pure bladder dysfunction. After rehabilitation, 28 (84.8%) of them were able to return to gainful employment within a year of their injuries. PMID- 1630841 TI - Human osteoblast stimulation by sera from paraplegic patients with heterotopic ossification. AB - The pathophysiology of heterotopic periarticular ossification is not understood. Though local agents may be responsible, factors present in the serum may be contributory. Sera from 4 paraplegic patients with heterotopic ossification and 4 'normal' paraplegics were incubated with human osteoblasts in tissue culture and their metabolic activity was measured quantitatively. There were significantly greater levels of osteoblast stimulating factors present in the sera of ossifying patients, (p less than 0.01). These factors may contribute to the pathogenesis of heterotopic ossification. PMID- 1630842 TI - Prophylactic low dose heparin anticoagulant therapy in patients with spinal cord injuries: a retrospective study. AB - A retrospective study was performed of 100 consecutive acute traumatic spinal injury patients with neurological deficit admitted to the Yorkshire regional spinal injuries centre prior to May 1990. Ninety-seven of these patients received prophylactic low dose subcutaneous heparin and 3 patients were excluded because of noted complications. Twenty-six patients developed thromboembolic complications. Apart from the fact that acute spinal cord injury patients are considered to be in an hypercoaguable state, the occurrence of deep vein thrombosis/pulmonary embolism (DVT/PE) in our study, even though these patients were on prophylactic low dose subcutaneous heparin, was related to delay in transfers, operative intervention, level of spinal cord injury and was possibly due to loss of some amount of heparin solution from the prefilled syringe during removal of air bubbles prior to the subcutaneous heparin injection. PMID- 1630843 TI - Suicide following acute traumatic spinal cord injury. AB - The rate of suicide following spinal cord injury has not been extensively studied but appears to be greater than in the general population. Six patients who died by suicide, from a total of 342 patients who were treated for acute spinal cord injury over a 5 year period are described. Clinical features shared by this group of patients included being male; having schizoid, depressive or narcissistic personality traits; alcohol or drug abuse; family or significant others favouring death as a preferred option; and the development of significant depression. PMID- 1630844 TI - Modified Brown-Sequard syndrome following coronary artery bypass graft: case report. AB - A 75 year old man underwent a triple coronary artery bypass graft performed with intra-aortic balloon pump assistance. Left leg weakness developed on the first postoperative day, progressive worsening occurred over the next 2 1/2 weeks, finally culminating in a modified Brown-Sequard pattern of deficit. No etiology was found. Previous reports of spinal cord injury following coronary artery bypass graft are reviewed and the microcirculation of the spinal cord is discussed. PMID- 1630845 TI - Brown-Sequard syndrome due to Semple antirabies vaccine: case report. PMID- 1630846 TI - The prevalence of hyperhidrosis in patients with spinal cord injuries and an evaluation of the effect of dextropropoxyphene hydrochloride in therapy. AB - The prevalence of annoying hyperhidrosis (HH) in patients with spinal cord traumatic lesions was investigated by a questionnaire. A total of 192 patients were sent the questionnaire, 154 patients answered, and 41 patients reported annoying sweating. Of these 41 patients, 13 had a somatic underlying cause and 28 indicated having annoying HH without a contributing somatic cause. Twenty-five patients with spinal cord injury (SCI) were included in a double-blind, randomized, placebo-controlled, crossover trial using dextropropoxyphene hydrochloride (DP) in a slow release form (Abalgin Retard 150 mg Benzon Pharma A/S, Copenhagen) twice a day, for the treatment of annoying HH. Nineteen patients with lesions between C4 and L4 completed the study. Eight found the active drug to be so effective that they wanted to continue the treatment while 3 preferred placebo. Six patients dropped out, 5 due to adverse effects. There was a trend towards an effect on sweating in daytime (p = 0.08-0.14). Given that the patients had a preference, which 15 of 19 had, the true frequency of patients preferring active treatment ranged from 32 to 84% (95% exact confidence limits). For those with SCI above T6 level the limits ranged from 40 to 97%. We conclude that in spite of the lack of statistically significant effect, it seems worthwhile to try DP for annoying HH, especially in patients with lesions above T6 level. PMID- 1630847 TI - Sexual issues of women with spinal cord injuries. AB - The need for research addressing problems unique to women with spinal cord injuries is well documented. Consequently, 231 such women, ages 18 to 45, were surveyed. Demographic characteristics and data relating to physician usage, female hygiene, pregnancy, contraception and sexuality were collected. Analysis revealed that 60% of the respondents had post injury amenorrhea; the average time until menses resumption was 5 months. The group's post injury pregnancy rate was one-third its pre injury rate, but women with incomplete paraplegia had significantly more pregnancies than those with complete quadriplegia. Of 47 women who did carry babies to delivery, one-half had vaginal deliveries; 49% used no anesthesia. Problems during pregnancy included autonomic hyperreflexia, decubitus ulcers, urinary tract infections, water retention, bladder and bowel problems, anemia, spotting, fatigue, cardiac irregularity and toxemia. Many of these problems plagued the women during labor and delivery and in the post partum period as well. Sixty-nine percent of the women were satisfied with their post injury sexual experiences, although self confidence, spasticity, and lack of spontaneity were issues. Although satisfied with care received from physicians, many women were not content with the information provided during rehabilitation, and felt a need for more literature, counselling, and peer support. PMID- 1630848 TI - Septic ischial bursitis in patients with spinal cord injury. AB - Septic ischial bursitis is described in 4 patients with spinal cord injury. In these patients a pre-existing ischial bursitis probably became secondarily infected. Because these patients lack sensation, diagnosis may be difficult. The disease process in one patient with a prolonged fever was only recognized after a leucocyte scan detected an abscess extending to the thigh. At surgery it was found that the infection extended from the ischial bursa to the upper lateral thigh. Infection in these patients was due to beta hemolytic streptococcus, S. aureus, and S. epidermidis. The patients all responded well to local drainage and excision of the bursa. PMID- 1630850 TI - Anourethral reflex. Description of a reflex and its clinical significance: preliminary study. AB - A new reflex which I call the 'ano-urethral reflex' is described and its clinical significance discussed. It was studied in 16 volunteers with normal vesical and rectal functions. A concentric needle electrode was introduced into the external and sphincter (stimulating), and another one into the external urethral sphincter (recording). The reflex response was recorded by EMG apparatus. The external urethral sphincter basal activity was increased with stimulation of the external anal sphincter. This reflex response was absent when the external and sphincter was anesthetised. The average latency of the reflex was 129.5 ms. Reflex urethral sphincter contraction at defecation guards against involuntary micturition which may result from rectal distension and levator contraction. The anourethral reflex can be a valuable diagnostic tool in routine investigations of patients with urological and proctological complaints. PMID- 1630849 TI - Increased serum osteocalcin levels in patients with paraplegia. AB - Osteocalcin(OC) is a specific serum parameter of bone formation. Since bone metabolism disturbances, including osteoporosis, are seen in paraplegia, the serum levels of OC, midregional parathyroid hormone(mPTH), intact para-thyroid hormone (iPTH) and calcitonin (CT) serum levels were determined in 13 patients with paraplegia or tetraplegia and 15 control subjects by radioimmunoassay in a cross sectional study. In addition, the urinary hydroxyproline/creatine and the urinary calcium/creatinine ratio was determined. Serum OC levels were significantly increased in the patients with spinal cord injury (p less than 0.02), whereas serum levels of mPTH, iPTH and CT were not statistically different. The urinary hydroxyproline/creatinine ratio was significantly higher in the patients than in the controls (p less than 0.02), and the urinary calcium/creatinine ratio also tended to be higher in the patients. In a follow up study over 6 months after spinal cord injury, serum OC, serum iPTH, urinary hydroxyproline/creatinine ratio and the calcium/creatinine ratio were determined in 6 patients at monthly intervals. Hyperhydroxyprolinuria preceded the gradual increase of serum OC from normal to clearly elevated levels. Our data suggest that increased bone resorption in paraplegia is linked to an enhanced osteoblastic activity. PMID- 1630851 TI - The social and vocational outcome of spinal cord injury patients. AB - Functional status, perception of adjustment, occupational outcome and social functioning were investigated in a group of spinal cord injury (SCI) patients (mean age 34, range 10-74 years) seen at a specialised spinal unit over the period January 1984-December 1988. Functional status was assessed using a standardised scale measuring patients' performance of specific tasks, and other measures of outcome were investigated by a structured interview. Almost two thirds (68%) of the patients were independent according to the standardised scale (33% quadriplegic and 84% paraplegic). Patients' autonomy appeared to be threatened by architectural barriers in and about the house: approximately one third (34%) of those classified as 'independent' on the standardised rehabilitation scale used needed some help in their everyday life. A negative occupational outcome emerged: compared to the pre-morbid situation, 43 patients (44%) were worse off; 48 (49%) did not experience substantial changes--though it must be noted that 68% of these (33/48) were virtually unemployed (ie student, home maker, retired, unemployed) before the injury; and for 6 (7%) some improvement took place. With a multivariate analysis age was the only statistically significant predictor of poor occupational outcome, with older patients being worse off irrespective of the extent of disease and functional autonomy. The paper discusses these results and stresses the need for integrating results based on the use of standardised rehabilitation scales with the analysis of potential barriers influencing a patient's ability to exploit his/her autonomy. PMID- 1630852 TI - The management of an old fused hip after the occurrence of paraplegia. AB - Two patients are reported who suffered traumatic paraplegia, and had a long standing fused hip joint. Both required an excision (Girdlestone) arthroplasty to allow them to sit and one, who made a late but substantial neurological recovery, eventually underwent a total hip replacement. Both suffered thromboembolic and urinary complications. These may not have occurred if the procedures had been carried out earlier. Early mobilisation of the hip joint is recommended in these circumstances. PMID- 1630853 TI - Electrical stimulation of the lumbrical muscles in an incomplete quadriplegic patient: case report. AB - The increasing number of incomplete cervical spinal cord injuries means that more attention needs to be focused on the rehabilitation of the incomplete quadriplegic hand. A case study, describing the application of electrical stimulation for strengthening the paretic lumbrical muscles, is presented. A 2 week strengthening program resulted in a 33% increase in the force produced by the lumbrical muscles. No loss of strength had occurred 4 weeks after cessation of the treatment. The magnitude and speed of this result should be of interest to those clinicians who seek to maximise patient independence in minimal time. PMID- 1630854 TI - Nosocomial urinary tract infections at a pediatric hospital. AB - Although the epidemiology of nosocomial urinary tract infections (NUTIs) is well described in the adult population, there is little information on children. We therefore reviewed all our patients with NUTIs, to determine their age, underlying diagnoses, microorganisms involved, use of catheters and secondary bacteremias. During a 2-year period at our institution, NUTIs accounted for 10% of all nosocomial infections (0.8 infections/100 admissions). Of 44,948 patients admitted during this period 0.7% (n = 318) acquired 351 episodes of NUTI. The patient ages ranged from 5 days to 21 years. The highest rates of NUTIs per ward (NUTI/100 admissions or transfers to the ward) were seen in the neonatal surgery (4.8), hematology/oncology (2.7), infant neurosurgery (2.1) and neonatal intensive care units (1.9). The most common organisms isolated were Escherichia coli (26%), Enterococcus sp. (15%), Pseudomonas sp. (13%), Klebsiella sp. (10%) and coagulase-negative Staphylococcus (9%). Catheterrelated infections accounted for 48% of all the NUTIs. Secondary bacteremia occurred rarely, with an incidence of 2.9% (n = 7). We conclude that NUTIs represent an important proportion (10%) of nosocomial infections in our population of hospitalized children, but secondary bacteremia is uncommon. PMID- 1630855 TI - Nontuberculous mycobacteria in children with acquired immunodeficiency syndrome. AB - Among 139 children with acquired immunodeficiency syndrome at Children's Hospital of New Jersey, 20 had positive cultures for non-tuberculous mycobacteria. Eighty five percent had Mycobacterium avium complex isolated and 70% had definite evidence of disseminated disease. Ninety-three percent had CD4 lymphocyte counts less than 100 cells/mm3 and 95% had met acquired immunodeficiency syndrome criteria before the time of first positive culture. Clinical findings included failure to gain weight, anorexia, fever, abdominal pain/tenderness and anemia. The median age at onset of symptoms was 46 months and the median time between onset of symptoms and positive culture was 9 months. Outcome for patients with positive cultures for nontuberculous mycobacteria was poor, with 75% of the children surviving for less than or equal to 10 months. Nontuberculous mycobacteria are increasingly important causes of morbidity and indirect mortality in human immunodeficiency-infected children. Children with severe immunodeficiency are at particular risk. In addition to M. avium complex, other species of nontuberculous mycobacteria may be involved. PMID- 1630856 TI - Pharmacokinetic study of piperacillin in newborns relating to gestational and postnatal age. AB - The pharmacokinetics of piperacillin after a single 75-mg/kg intravenous injection as analyzed in 28 neonates with gestational ages of 29 to 40 weeks (A = 29 to 31 weeks, B = 33 to 35 weeks, C = 38 to 42 weeks) and birth weights of 860 to 3900 g during 35 courses. Serum concentrations of piperacillin were determined by high pressure liquid chromatography. A one compartment open model characterized the disposition of piperacillin. Twenty courses were given between Day 3 and Day 5 of life. The elimination half-life and total body clearance were related to gestational age. Differences were significant between Groups A and B and Group C for half-life (4.3 +/- 1.9 and 3.35 +/- 0.75 vs. 2.47 +/- 0.72 hours) and for clearance (1.68 +/- 0.6 and 1.8 +/- 0.4 vs. 2.46 +/- 0.36 ml/min/kg). Volumes of distribution were similar in the 3 groups, from 516 +/- 108 to 633 +/- 226 ml/kg. Fourteen courses were given from Day 9 to Day 11 of life. The same differences were observed between Groups A and B and Group C. Elimination half life was significantly reduced with simultaneous increase of the total body clearance. In clinical practice, 75-mg/kg intravenous injections every 12 hours during the first week of life and every 8 hours in the second week provide appropriate concentrations in infants of less than 36 weeks gestational age. In full term newborns the 75-mg dosage is appropriate but the number of injections must be increased to 3/24 h for the first week and 4 times daily thereafter. PMID- 1630857 TI - Efficacy of Haemophilus influenzae type b vaccines in Massachusetts children 18 to 59 months of age. AB - Since 1987 Haemophilus influenzae b (Hib) conjugate vaccines have been licensed for use in children ages 18 months and older. Before licensure there were no clinical trials of a single dose of any conjugate vaccine in children ages 18 months or older. To fulfill this need we performed an age- and residence-matched case-control study of the efficacy of Hib vaccines. In our study population the protective efficacy (PE) of Hib-diphtheria toxoid conjugate vaccine was 88% (95% confidence interval, 45 to 98%). No vaccine failures were observed with Hib oligosaccharide CRM197 diphtheria protein conjugate vaccine, but usage was not sufficient to establish efficacy: PE = 100% (95% confidence interval, -37 to 100%). The protective efficacy of Hib capsular polysaccharide vaccine was 18% (95% confidence interval -487 to 89%). We conclude that for children ages 18 to 60 months a single dose of the Hib conjugate vaccine, PRP-D, is protective against invasive Hib infections. Consistent with most studies Hib polysaccharide vaccine provided suboptimal protection. PMID- 1630858 TI - Interrelationship between diarrhea and vitamin A deficiency: is vitamin A deficiency a risk factor for diarrhea? AB - A cross-sectional study, a follow-up study and an evaluation of impact of community-based distribution of vitamin A capsules (200,000 IU) were conducted in Omdurman (Sudan) between November, 1988, and March, 1989. In the cross-sectional survey 1441 children less than 5 years of age participated, which established the baseline values for plasma retinol-binding protein. During the follow-up period 290 cases of diarrhea occurred. Low concentrations of plasma retinol-binding protein (less than 1.85 mg/dl) proved to be a risk factor for diarrhea, especially in girls. The relative risk increased after the second year of life. Children who received vitamin A supplementation before commencement of the study had a lower incidence of diarrhea. The protective effect of vitamin A supplementation was greater in girls (relative risk, 0.297; 95% confidence interval, 0.240 to 0.368) than in boys (relative risk, 0.404; 95% confidence interval, 0.352 to 0.464). PMID- 1630859 TI - Analysis of a measles outbreak in Kent County, Michigan in 1990. AB - New recommendations from the Immunization Practices Advisory Committee call for a second dose of measles vaccine for school age children. The purpose of this paper is to demonstrate the need for additional measures for the protection of preschool age children. A hospital-based measles outbreak of 25 cases in Kent County, MI, in 1990 provided an opportunity to study measles transmission to preschool age children. Twenty-two (88%) were people who had never received measles vaccine. Twelve of the cases were unvaccinated preschoolers, seven of whom were older than 15 months. Three nonvaccinated, but eligible people (one philosophic exemption and two vaccine-eligible preschoolers) were the source of most of the other cases. One school age unvaccinated child died of measles pneumonitis. A telephone survey indicated that improved public education regarding indications and contraindications to vaccination might encourage vaccination of children according to public health recommendations. PMID- 1630860 TI - Biology and molecular biology of human immunodeficiency virus. PMID- 1630862 TI - Disseminated Acanthamoeba infection in a child with symptomatic human immunodeficiency virus infection. PMID- 1630861 TI - Inherited C3 deficiency and meningococcal disease in a teenager. PMID- 1630863 TI - Ciprofloxacin treatment of multiply drug-resistant extrapulmonary tuberculosis in a child. PMID- 1630864 TI - Tuberculous peritonitis in a three-year-old boy: case report and review of the literature. PMID- 1630865 TI - Sinusitis and bacteremia caused by Flavobacterium meningosepticum in a sixteen year-old with Shwachman Diamond syndrome. PMID- 1630866 TI - Congenital staphylococcal scaled skin syndrome: report of a case. PMID- 1630867 TI - Imipenem therapy for melioidosis in two children. PMID- 1630868 TI - Prolonged fever in a 21-month-old boy. PMID- 1630869 TI - Maternal-infant transmission of hepatitis C virus infection. PMID- 1630870 TI - Significance of viridans streptococci in blood cultures from children. PMID- 1630871 TI - Ciprofloxacin therapy for localized melioidosis. PMID- 1630872 TI - Varicella in children receiving steroids for asthma: risks and management. PMID- 1630873 TI - Synopsis Book. Best articles relevant to pediatric allergy and immunology. Abstracts. PMID- 1630874 TI - Platinum antitumour agents: a review of (bio)analysis. AB - This paper summarizes analytical techniques in order to get a clear picture of the ins and outs of the (bio)analysis of platinum-containing compounds. The antitumour agent cisplatin has become an indispensable drug for the cure of a variety of cancer diseases. Since its introduction in the early seventies, about 2,000 related platinum complexes were designed to devoid the dose-limiting nephrotoxicity. Some of them were introduced for clinical trial, such as carboplatin and iproplatin. To investigate the mechanism of action and pharmaco kinetic behaviour, several interesting assays for total and specific platinum determination in biological matrices have been developed, each with its own possibilities and limitations. PMID- 1630875 TI - Clinical and pharmaceutical aspects in acute poisoning. AB - Today there are several methods for treating intoxicated patients. If these patients arrive in hospital in time, the diagnosis is correct and appropriate therapy is instituted, nearly all survive without any physical damage. This is best achieved by team-work between the hospital pharmacist and the physician treating the patient. Both should have a sound knowledge of the toxicological properties of drugs and other poisons and the clinical features which they produce. This article emphasizes the need for close co-operation between the pharmacist and the physician and discusses specific therapeutic measures, such as prevention of absorption, acceleration of elimination, symptomatic therapy and administration of antagonists. PMID- 1630876 TI - Direct measurement of probenecid and its glucuronide conjugate by means of high pressure liquid chromatography in plasma and urine of humans. AB - Probenecid with its phase-I metabolites, and phase-II glucuronide conjugate can be analysed by a gradient high pressure liquid chromatographic method. Probenecid glucuronide in plasma with pH 7.4 is not stable and declines to 10% of the original value within 6 h (t1/2 approximately 1 h). Probenecid glucuronide is stable in urine with pH 5.0, moderately unstable at pH 6.0 (t1/2 approximately 10 h), and unstable at pH 8.0 (t1/2 approximately 0.5 h). Probenecid glucuronide is stable in water and 0.01 mol/l phosphoric acid in the autosampler of the high pressure liquid chromatograph. The decrease in concentration in water is 5.5% during 9 h and 0% in diluted acid. Probenecid glucuronide and the phase-I metabolites were not detectable in plasma. The main compound in fresh urine is the phase-II conjugate probenecid glucuronide (62% of a 500 mg dose); the phase-I metabolites are present and only a trace of probenecid is present. The percentage of the dose of the phase-I metabolites varies between 5 and 10, while hardly any probenecid is excreted unchanged (0.33%). PMID- 1630877 TI - Centralized preparation of hazardous drugs. A choice between isolator and laminar airflow. AB - In 1987, the manager of the Saint-Joseph Hospital (Paris, France) requested a reorganization of cytotoxic drug preparation. Protection for staff who handle hazardous drugs was the main concern. The conclusions drawn from a first analysis emphasize the advantages of a centralized reconstitution unit against a decentralized system. Subsequently, a workload study and an economic study (investment, maintenance, supplies, staff costs, comparative balance sheet and a 5-year simulation) were carried out, but to choose between a laminar airflow in aseptic room and an isolator in a conventional room. The selected isolator is the first of the conception: the central half-suit uses as a server, and four sleeves located on one side allow two technicians to work in a sterile and closed area without sterile garments. PMID- 1630878 TI - Hydrocortisone anaphylaxis: a new case report. AB - In this report we describe a case of a nonatopic patient who developed an anaphylactoid reaction immediately after receiving intravenous hydrocortisone. The patient recovered after reanimation techniques and intravenous administration of atropine, epinephrine and plasma expanders. Although allergic reactions to corticosteroids appear to be rare there are a few case reports in the literature. This case is presented to draw the attention of clinicians to the occasional hazard of intravenous corticosteroid preparations, specially hydrocortisone. PMID- 1630879 TI - Influence of caffeine, Ca2+, and Mg2+ on ryanodine depression of the tension transient in skinned myocardial fibers of the rabbit. AB - Ryanodine, a blocker for Ca(2+)-release channels of the sarcoplasmic reticulum (SR Ca(2+)-release channels), induces depression of myocardial contraction in isolated intact muscle, which is consistent with depression of the caffeine induced tension transient in skinned muscle fibers. In isolated SR, ryanodine binds to a specific receptor with high affinity, and this binding is enhanced by caffeine and increasing Ca2+ and decreased by increasing Mg2+. The aim of this study was to test the hypothesis that depression of myocardial contraction is mediated by changes in ryanodine-receptor binding properties. Accordingly, factors (caffeine, Ca2+, and Mg2+) affecting ryanodine-receptor binding properties in the isolated SR membrane were studied in skinned myocardial fibers from adult rabbits. The depression of the caffeine-induced tension transient by ryanodine (ryanodine depression) influenced by these three factors was measured. In a dose-dependent manner, increasing caffeine or Ca2+ concentrations enhanced the ryanodine depression. The concentrations for 50% ryanodine depression (IC50) approximated 7 mM for caffeine, and pCa 5.25 for Ca2+. When 1 microM ryanodine and 25 mM caffeine were combined, ryanodine depression was independent of Ca2+ at low Ca2+ concentrations (20%-30% at pCa greater than 8 and 7.5) and was a direct function of Ca2+ at higher concentrations (pCa 7.5-6.0 with IC50 approx. pCa 6.75). In contrast, increasing Mg2+ reduced the ryanodine depression with IC50 approximately equal to pMg 3.3. In conclusion, the caffeine- or Ca(2+)-enhanced, and Mg(2+)-reduced ryanodine depression observed in this study is consistent with known ryanodine-receptor binding properties. PMID- 1630880 TI - Water handling in the rat jejunum: effects of acidification of the medium. AB - The minute-by-minute net water movement (Jw) in the rat jejunum was studied in relation to the diffusive water (Pw) and mannitol (Ps) permeabilities with the following results. (a) Jw was a linear function of the applied hydrostatic and osmotic transepithelial gradients (hydrostatic permeability coefficient, Phydr = 0.052 +/- 0.011 cm s-1; osmotic permeability coefficient, Posm = 0.0069 +/- 0.0014 cm s-1. (b) A fraction of this absorptive Jw (transport-associated Jw, Jwt = 0.086 +/- 0.024 microliter min-1 cm-2) was independent of the presence of any osmotic, hydrostatic or chemical gradient. (c) In the absence of Na+, Jwt was not significantly different from zero and there was an increase in Phydr but no change in Posm. (d) In the presence of a hydrostatic gradient (10 cm H2O, mucosal side), acidification of the medium (95% CO2 bubbling, pH 6.2) simultaneously and reversibly increased Jw and decreased Pw. (e) When an osmotic gradient was present (40 mM polyethyleneglycol on the serosal side) a net increase in Jw was observed. CO2 bubbling in these conditions reversibly reduced Jw while increasing Ps. (f) These effects were not observed when the serosal or mucosal pH was reduced in the presence of a nonpermeant buffer (HEPES/TRIS; MES/TRIS). If we accept that Ps is a good marker of paracellular movements and that Pw mainly reflects transcellular water movements, we may conclude that acidification of the medium, in the presence of bicarbonate, modifies both paracellular and transcellular routes. The experimental evidence indicates that an increase in proton concentration opens the paracellular pathway and probably has a blocking effect on a transcellular route. PMID- 1630881 TI - Tedisamil inhibits the delayed rectifier K+ current in single smooth muscle cells of the guinea-pig portal vein. AB - Tedisamil is a new bradycardic agent with an inhibitory action on K+ channels in cardiac muscle, and secondary beneficial effects in experimentally induced cardiac ischemia. In whole-cell clamp studies in enzymatically dispersed, single smooth muscle cells from the guinea-pig portal vein, tedisamil inhibited the delayed rectifier K+ current (determined as the charge transferred through the cell membrane), the mean concentration for half-maximal inhibition being 2.9 microM. In contrast to controls in the absence of drugs or in the presence of the classical K+ channel blockers barium, tetraethylammonium or 4-aminopyridine, the time course of the delayed rectifier K+ current in the presence of tedisamil could no longer be fitted by a single exponential, and signs of an accelerated inactivation by tedisamil were obtained. The slow onset of the response to tedisamil applied to the outside of the vascular myocytes, and the finding that tedisamil applied directly to the cytosol via the pipette was highly effective, suggest an intracellular site of action. PMID- 1630882 TI - Thyroid control of contractile function and calcium handling in neonatal rat heart. AB - Newborn rats were rendered hyperthyroid (daily subcutaneous injections of L triiodothyronine, 10 micrograms 100 g-1 body weight) or hypothyroid (0.05% 6-n propyl-2-thiouracil in drinking water to nursing mothers) during the first 3 weeks of postnatal life. Compared with the euthyroid group, hyperthyroidism resulted in: (1) cardiac enlargement with right ventricular preponderance, (2) increased cardiac contractile function, (3) increased Ca2+ uptake by the sarcoplasmic reticulum (SR), (4) decreased sensitivity to the negative inotropic effect of verapamil and (5) greater inhibition of contractile function by ryanodine. Hypothyroidism generally resulted in opposite changes. The data suggest that the development of the heart and its contractile function during early postnatal life depends on the plasma level of thyroid hormones. In particular, the relative contribution of the SR and sarcolemmal Ca2+ transport to the control of cardiac contractility seems to be markedly affected by altered thyroid states. The postnatal maturation of the SR function is accelerated in hyperthyroidism but retarded in hypothyroidism. Consequently, hyperthyroid hearts appear to be less dependent and hypothyroid ones more dependent on trans sarcolemmal Ca2+ fluxes when compared with age-matched euthyroid animals. PMID- 1630883 TI - Active movement of cardiac myosin on Characeae actin cables. AB - The active sliding of cardiac myosin on actin cables was studied using an in vitro movement assay. Cardiac myosin prepared from either adult rabbit or rat hearts was mixed with small latex beads to coat them. Actin cables were obtained from the internodal cells of green algae, Characeae. When the myosin-coated beads suspended in physiological buffer were introduced into the internodal cells, the myosin started to interact with the actin causing the beads to move. The sliding movement of the beads was observed under microscopy and the sliding velocity measured. The observed movement was smooth and the velocity was constant over a long distance. The movement was physiological in nature: a) it was ATP-dependent, but above a certain level of ATP, the velocity was constant; b) the velocity was maximum at pH 7.0, and decreased in both acidic and alkaline conditions. The average sliding velocity of cardiac myosin obtained from rabbit ventricles (0.31 +/- 0.11 micron/s) was slower than that from rat ventricles (1.04 +/- 0.26 micron/s) reflecting the lower ATPase activity of rabbit cardiac myosin. This assay system is considered to be a useful tool linking biochemistry and physiology at the molecular level. PMID- 1630884 TI - Relationship between force and Ca2+ in anococcygeal and vas deferens smooth muscle cells of the mouse. AB - We compared the changes of the cytoplasmic Ca2+ concentration ([Ca2+]i), as measured with the fluorescent Ca2+ indicator fura-2, and the force development in intact smooth muscle of the tonic anococcygeus (AC) and the phasic vas deferens (VD) of the mouse, during activation by K+ depolarization and by agonists. Resting [Ca2+]i was observed to be 33% lower in AC (80 nM) than in VD (115 nM), while the Ca2+ threshold for contraction was found to be about 120 nM in AC and 160 nM in VD. For a similar [Ca2+]i increase, the agonist stimulation induced a higher force development than the K+ depolarization in both muscle types. During prolonged depolarization, the force/calcium ratio increased in AC but strongly declined in VD. This decline of the force/calcium ratio in VD during depolarization was partially reversed by lowering [Ca2+]o. Our results indicate that the Ca2+ threshold for force development was about 150% of the resting [Ca2+]i in both cell types. The resting [Ca2+]i was lower in the tonic AC than in the phasic VD. Agonist-induced sensitization to Ca2+ occurred in both muscle types. The tonic and phasic smooth muscles essentially differed in the respective modulation of their Ca2+ sensitivity during contraction. The desensitization to Ca2+ was specific for phasic muscle, in which it occurred as an early, time- and Ca(2+)-dependent process that was partially reversible. PMID- 1630887 TI - Size and chirality of intracellularly applied anions affect the function of isolated photoreceptors. AB - The effect of intracellularly applied anions on the function of retinal rods of the frog Rana esculenta was investigated by means of the whole-cell patch-clamp technique. When the recording pipette contained a medium based on potassium chloride, a slow spontaneous hyperpolarization was observed presumably due to a diffusional loss of the photoreceptor's internal transmitter cyclic guanosine monophosphate (cGMP) and its precursor guanosine triphosphate (GTP). When chloride was replaced by organic anions such as acetate, aspartate, or gluconate the speed of hyperpolarization diminished and the dark voltage of the rods was stabilized. The extent of stabilization correlates with the molecular weight of the anions. A significant difference in the stabilizing effect was found for L aspartate and D-aspartate, suggesting an additional influence of the chirality. Effects of some of the anions on the configuration of the light responses were also observed. PMID- 1630885 TI - Cromakalim and lemakalim activate Ca(2+)-dependent K+ channels in canine colon. AB - The effects of cromakalim (BRL 34915) and its (-) optical isomer, lemakalim (BRL 38227) on the activity of 265-pS Ca(2+)-activated K+ channels (BK channels) were examined in cell-attached and inside-out patches from canine colonic myocytes. In cell-attached patches lemakalim increased the open probability (Po) of BK channels. Mean NPo, where N is the number of channels per patch, at +50 mV increased from 0.08 to 0.26 (20 microM lemakalim). In inside-out patches, cromakalim and lemakalim increased channel NPo rapidly and reversibly. This increase in NPo was due to a shift in half-maximal activation. Glyburide (20 microM) prevented the increase in NPo caused by lemakalim in cell-attached patches and reversed the increase in NPo in inside-out patches. Under conditions where Ca(2+)-activated K+ channels were maximally activated, lemakalim failed to increase current or induce a second type of K+ channel activity. When tetraethylammonium (200 microM) was added to the pipette solution to block the BK channel half maximally, lemakalim also failed to induce a second type of channel. Adenosine triphosphate (1 or 2 mM) applied to the inner surface of inside-out patches had no effect on Po of BK channels. Finally, the effects of lemakalim on ensemble average currents, constructed from multiple openings of BK channels in cell-attached patches was found to successfully mimic the effects of the drug on whole-cell membrane currents. We conclude that cromakalim and lemakalim activate BK channels in canine colonic cells. Whether this action participates in the membrane hyperpolarization and the decrease in frequency and duration of slow waves produced by these compounds in intact colonic muscles remains to be investigated. PMID- 1630886 TI - Effects of endurance training on myosin heavy-chain isoforms and enzyme activity in the rat diaphragm. AB - We investigated the effects of endurance training (20 m/min, 60 min/day, 5 days/week) on myosin heavy-chain (MHC) isoforms and succinic dehydrogenase (SDH) activity in rat crural and costal diaphragms, and plantaris muscles. Although the 4-week endurance training produced significant (P less than 0.05) increases, both in SDH activity and the percentage of isoform HCIIa in the plantaris of the trained rat compared with the sedentary control rat, these alterations did not occur in either the crural or costal diaphragms. After 10 weeks of endurance training, trained animals had significantly (P less than 0.05) higher SDH activity in the costal diaphragm and the plantaris. Moreover, a significant (P less than 0.05) decrease occurred in the percentage of HCIIb in the costal diaphragm, and a significant (P less than 0.01) decrease in the percentage of HCIIb concomitant with a significant (P less than 0.05) increase of HCIIa resulted in the plantaris. However, the crural diaphragm did not show any significant changes after 10 weeks of endurance training. These results indicate that endurance training induces an alteration in the expression of an MHC phenotype, in addition to causing an increase in oxidative enzyme activity. However, the alterations in response to endurance training are apparently not uniform, varying between regions and/or kinds of muscles. PMID- 1630888 TI - [MR imaging of amyotrophic lateral sclerosis]. AB - Magnetic resonance imaging (MR imaging) provides a sensitive method for mapping the normal and pathological distribution of iron in the brain. High field strength MR imaging (1.5 T) was used to evaluate eight patients with amyotrophic lateral sclerosis (ALS) and 49 neurological normal control patients. All eight ALS patients showed decreased signal intensity in the motor cortex on T2-weighted images, while only one of the normal control patients showed this finding. The results suggested that the decreased signal intensity in the motor cortex in ALS was caused by the deposition of iron in this area. PMID- 1630889 TI - [US findings of junctional parenchymal defect of the kidney]. AB - Junctional parenchymal defect (JPD) is a triangular or linear hyperechoic structure in the anterosuperior or posteroinferior surface of the kidney. The intermediate septum is a band-like cortex, running obliquely in the central echo complex. Some authors have suggested that these structures result from partial fusion of the embryonic parenchymatous masses called renunculi (renunculi theory). In a prospective study of 600 adult patients, the anterosuperior JPD of the right kidney was most frequently identified on ultrasonography (33.5%). The incidence of JPD did not depend on sex or age, and intermediate septum was frequently associated with JPD (71.4%). These data are compatible with the renunculi theory. The prominent septum of Bertin was located in the same position on the intermediate septum in the majority of cases (96.7%). Therefore, we suggest that the typical prominent septum of Bertin may be an incomplete intermediate septum. In order to differentiate JPD from pathologic conditions such as cortical scar or hyperechoic tumor, it is necessary to identify its characteristic location and shape. PMID- 1630890 TI - [Evaluation of transcatheter arterial embolization with coaxial microcatheter and micro-coil for vascular lesions]. AB - Transcatheter arterial embolization using a coaxial microcatheter and micro-coil was performed in eight patients with vascular lesions; one each with aneurysm of the basilar artery, cerebellar artery, and pancreatic artery, pseudoaneurysm of the common hepatic artery, gastroduodenal artery, and gluteal artery, carotid cavernous fistula, and thoracic paraspinal arteriovenous malformation. Complete occlusion was achieved in five patients with aneurysm and pseudoaneurysm by occluding the aneurysmal cavity and/or the orifice. A patient with recurrent carotid-cavernous fistula was also completely embolized. A case of basilar artery aneurysm resulted in partial occlusion because the posterior cerebral artery originated from the aneurysm. The unsatisfactory result in a case of paraspinal AVM was due to its wide extension with multiple feeding arteries. No apparent complication was seen. In conclusion, super-selective arterial embolization therapy with coaxial microcatheter and micro-coils was found to be a useful method for vascular lesions that would have been technically difficult to embolize with the standard catheter and coils. PMID- 1630891 TI - [Radiation therapy for patients with obstructive jaundice caused by carcinoma of the extrahepatic biliary system]. AB - From February 1980 through September 1990, 92 patients with obstructive jaundice resulting from biliary tract cancer registered at Shikoku Cancer Center Hospital or Ehime University Hospital. Radiation therapy (RT) was used to treat 38 of these patients (30 with carcinoma of the extrahepatic bile duct, excluding ampulla of Vater, and eight patients with carcinoma of the gallbladder). Of 38 patients, 11 underwent intraoperative radiation therapy (IORT), and 27 were treated by external radiation therapy (ERT) alone. In contrast, 54 patients (39 with carcinoma of the extrahepatic bile duct and eight with carcinoma of the gallbladder) were not treated by RT. All jaundiced patients received external and/or internal biliary drainage of some kind. Among patients undergoing biliary drainage with a catheter, 21 patients who underwent RT (four with IORT) survived significantly longer than 19 patients who did not (generalized Wilcoxon test: p less than 0.05). There were no significant differences in survival between 7 patients with recanalization and 11 patients with no recanalization. Concerning the survival of laparotomized patients, excluding those with complete resection or perioperative death, eight patients treated with postoperative ERT survived longer than 12 patients who did not have postoperative ERT (not significantly). Eleven patients underwent IORT. A patient with unresectable carcinoma of the hilar bile duct survived 2 years and 3 months after a combination treatment of ERT and IOTR. In four of eight autopsied patients, radiation effects of Grade II were observed (Oboshi and Shimosato's evaluation system for the histological effects of radiation therapy). Our experience suggests that RT is effective in patients with obstructive jaundice caused by carcinoma of the biliary system. PMID- 1630892 TI - [Thermoradiotherapy for adenocarcinoma of the rectum and sigmoid--application to primarily inoperable and recurrent cases]. AB - Between February 1983 and May 1990, 19 rectal cancers and three sigmoid colon cancers were treated with thermoradiotherapy. Among four patients with primary rectal cancer, one received preoperative treatment and three were judged inoperable. All the inoperable patients responded well to treatment and were judged operable. Pathological examination of the resected specimens confirmed the effectiveness of treatment. In one case in particular, no cancer cells were observed in the specimen or at autopsy, 21 months after thermoradiotherapy. Eighteen cases of recurrent colorectal cancer were also treated. Judged by tumor shrinkage alone, these patients were classified into five cases of PR and 13 of NR. When the low density area seen on CT images after treatment was added to the criteria, there was one case of CR, six of PR, and 11 of NR, and the effectiveness ratio shown by the sum of CR and PR was 38.9%. Fourteen cases in the thermoradiotherapy group and 16 in the radiation therapy group were compared as to the reduction in postoperative perineal pain caused by recurrence at the pre-sacral area. It was found that thermoradiotherapy was significantly superior to radiation therapy in the frequency and duration of pain relief. Although most patients complained of the sensation of heat, this was within tolerable limits, and no severe side effects were experienced. PMID- 1630893 TI - [Long-term results of radiotherapy in stage I.II glottic carcinoma]. AB - From 1965 to 1987, 271 patients were treated. Two hundred and sixty-two were male, and 9 were female. Age ranged from 36 to 91 years with a median value of 62 years. According to the UICC classification in 1987, 149 were T1a, 56 were T1b, 66 were T2. T2 was divided into T2a (with normal cord mobility), and T2b (with impaired cord mobility). Forty-seven were T2a and 19 were T2b. Total dose ranged from 24 to 84 Gy, and 245 received 60 Gy or more. Daily dose was 2 Gy in 249, and 3 Gy in 22. Field size ranged from 10 to 117 cm2. All 271 patients were treated with 6-MV X-ray. Adjuvant chemotherapy was performed in 91 patients. Follow-up was complete in 269 of 271 patients (99%). Eighty-four patients died of intercurrent disease. Thirty out of 84 (36%) died of second malignancy. A 10-year overall survival rate in 271 patients was 64% and a 10-year cause-specific survival rate (CSSR) was 92%. Ten-year CSSR were 94% in T1a, 92% in T1b, 90% in T2a, and 80% in T2b. Five-year local control rates were 87%, 77%, 84%, and 68%, respectively. Five patients relapsed after 5 years. Ten-year local control rates were 85%, 74%, 80%, and 68%, respectively. There seemed to be no relationship between local control rates and total dose, field size, TDF, and use of chemotherapy. Daily doses of more than 3 Gy seemed to increase complication rates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1630894 TI - [Usefulness of 111In labeled leukocytes scintigraphy combined with 99mTc phytate liver scintigraphy for diagnosis of hepatic abscess comparing with CT and US]. AB - 111In labelled leukocyte scintigraphy (ILLS) was performed in five patients with hepatic abscess. For the accurate diagnosis of hepatic abscess, ILLS was superimposed on 99mTc phytate liver scintigraphy. The results of ILLS were compared with CT and US findings. Four of five patients (80%) showed abnormal accumulations in the liver. The smallest abscess detected was 46 mm x 43 mm. CT scan showed rim enhancement, which was a specific finding for hepatic abscess, in three patients. It was rather difficult to diagnose hepatic abscess by US. In two cases without definite rim enhancement on CT, the abscesses were diagnosed as hot spots by ILLS. We conclude that ILLS combined with 99mTc liver scintigraphy is useful for the diagnosis of hepatic abscess. PMID- 1630895 TI - [Experimental study of water jet angioplasty]. AB - A newly invented angioplasty by using water jet energy was investigated for evaluating its safety and effectiveness in 3 dogs. The water jet was produced from a small tip nozzle (0.2 mm in diameter) of catheter by injecting 20 ml of diluted contrast medium. By using this method recanalization of femoral arterial occlusion produced by fresh thrombi was achieved in all 3 dogs. Post recanalization angiography showed no apparent small vessel occlusions. Injection apart more than 5 mm from the inner surface of human aorta provoked no apparent changes histopathologically. Water jet angioplasty may be useful in treating vascular occlusive disease. PMID- 1630896 TI - [Potential usefulness of computer-aided diagnosis (CAD) in a mass survey for lung cancer using photo-fluorographic films]. AB - We investigated the potential usefulness of computer-aided diagnosis (CAD) in a mass survey for lung cancer. When the sensitivity of the computer output was adjusted nearly equal to that of the mass survey in our database which contained 198 photofluorographic films, some shadows detected by the computer output were different from those detected by human observers. Therefore, the best estimated sensitivity of an observer using the computer output was equal to or greater than the sensitivity of double reading. It is expected that CAD may have a role in a mass survey for lung cancer using photofluorographic films. PMID- 1630897 TI - [Quantitative evaluation of liver function using 99mTc-GSA in rats with liver injury induced by ischemia-reperfusion]. AB - We evaluated quantitatively the liver injury of rats induced by ischemia reperfusion, using 99mTc-DTPA-Galactosyl-Human-Serum-Albumin (99mTc-GSA). The vessels of the left lobe were clamped for 5, 10, or 45 minutes followed by 15 minutes reperfusion. Then, 99mTc-GSA was intravenously administered (170 micrograms/kg body weight) to rats. Two compartment analysis was made on measurement curves in the heart and liver to obtain clearance parameters. Significant difference was observed between the ischemic group (clamped for 10 and for 45 minutes) and the control. These results suggest that 99mTc-GSA is useful in the estimation of liver injury produced by ischemia-reperfusion. PMID- 1630898 TI - 7-Deaza-2'-deoxyadenosine and 3-deaza-2'-deoxyadenosine replacing dA within d(A6) tracts: differential bending at 3'- and 5'-junctions of d(A6).d(T6) and B-DNA. AB - 7-Deaza-2'-deoxyadenosine (1, c7Ad) and 3-deaza-2'-deoxyadenosine (2, c3Ad) have been incorporated into d(AAAAAA) tracts replacing dA at various positions within oligonucleotides. For this purpose suitably protected phosphonates have been prepared and oligonucleotides were synthesized on solid-phase. The oligomers were hybridized with their cognate strands. The duplexes were phosphorylated at OH-5' by polynucleotide kinase and self-ligated to multimers employing T4 DNA ligase. Oligomerized DNA-fragments were analyzed by polyacrylamide gel electrophoresis and the bending was determined from anomalies of electrophoretic mobility. Replacement of dA by c3Ad decreased the bending more than replacement by c7Ad. Reduction of bending was much stronger when the modified nucleosides replaced one or several dA residues at the 3'-site of an d(AAAAAA)-tract whereas replacement at the 5'-site showed no significant influence [1, 2]. PMID- 1630899 TI - Conserved sequence motifs in the initiator proteins for rolling circle DNA replication encoded by diverse replicons from eubacteria, eucaryotes and archaebacteria. AB - An amino acid motif was identified that consists of the sequence HisHydrHisHydrHydrHydr (Hydr--bulky hydrophobic residue) and is conserved in two vast classes of proteins, one of which is involved in initiation and termination of rolling circle DNA replication, or RCR (Rep proteins), and the other in mobilization (conjugal transfer) of plasmid DNA (Mob proteins). Based on analogies with metalloenzymes, it is hypothesized that the two conserved His residues in this motif may be involved in metal ion coordination required for the activity of the Rep and Mob proteins. Rep proteins contained two additional conserved motifs, one of which was located upstream, and the other downstream from the 'two His' motif. The C-terminal motif encompassed the Tyr residue(s) forming the covalent link with nicked DNA. Mob proteins were characterized by the opposite orientation of the conserved motifs, with the (putative) DNA-linking Tyr being located near their N-termini. Both Rep and Mob protein classes further split into several distinct families. Although it was not possible to find a motif or pattern that would be unique for the entire Rep or Mob class, unique patterns were derived for large subsets of the proteins of each class. These observations allowed the prediction of the amino acid residues involved in DNA nicking, which is required for the initiation of RCR or conjugal transfer of single-stranded (ss) DNA, in Rep and Mob proteins encoded by a number of replicons of highly diverse size, structure and origin. It is conjectured that recombination has played a major part in the dissemination of genes encoding related Rep or Mob proteins among the replicons exploiting RCR. It is speculated that the eucaryotic small ssDNA replicons encoding proteins with the conserved RCR motifs and replicating via RCR-related mechanisms, such as geminiviruses and parvoviruses, may have evolved from eubacterial replicons. PMID- 1630900 TI - SRF and MCM1 have related but distinct DNA binding specificities. AB - The mammalian transcription factor SRF and the yeast regulatory protein MCM1 contain DNA binding domains that are 70% identical; moreover, both proteins can bind the serum response element in the human c-fos promoter. Here we present an analysis of MCM1 sequence specificity by selection of sites from random sequence oligonucleotides. In this assay the MCM1 DNA binding domain selects binding sites containing the consensus (NotC)CCY(A/T)(A/T)(T/A)NN(A/G)G, distinct from the SRF binding consensus CC(A/T)6GG. Carboxylethylation interference analysis of a set of selected sites suggests that MCM1 contacts DNA in its major groove throughout one helical turn. These differences in specificity are largely due to sequence differences between the N terminal basic parts of the SRF and MCM1 DNA binding domains. Comparison of the relative binding affinities of MCM1 and SRF for a panel of representative binding sites showed that many high affinity MCM1 sites have negligible affinity for SRF and vice versa. Thus MCM1 and SRF have significantly different sequence specificities. PMID- 1630901 TI - Systematic sequencing of the Escherichia coli genome: analysis of the 0-2.4 min region. AB - A contiguous 111,402-nucleotide sequence corresponding to the 0 to 2.4 min region of the E. coli chromosome was determined as a first step to complete structural analysis of the genome. The resulting sequence was used to predict open reading frames and to search for sequence similarity against the PIR protein database. A number of novel genes were found whose predicted protein sequences showed significant homology with known proteins from various organisms, including several clusters of genes similar to those involved in fatty acid metabolism in bacteria (e.g., betT, baiF) and higher organisms, iron transport (sfuA, B, C) in Serratia marcescens, and symbiotic nitrogen fixation or electron transport (fixA, B, C, X) in Azorhizobium caulinodans. In addition, several genes and IS elements that had been mapped but not sequenced (e.g., leuA, B, C, D) were identified. We estimate that about 90 genes are represented in this region of the chromosome with little spacer. PMID- 1630902 TI - Mapping of a Physarum chromosomal origin of replication tightly linked to a developmentally-regulated profilin gene. AB - We compared the pattern of replication of two cell-type specific profilin genes in one developmental stage of the slime mold Physarum polycephalum. Taking advantage of the natural synchrony of S-phase within the plasmodium, we established that the actively transcribed profilin P gene is tightly linked to a chromosomal replication origin and is replicated at the onset of S-phase. In contrast, the inactive profilin A gene is not associated with a replication origin and it is duplicated in mid S-phase. Mapping by two-dimensional gel electrophoresis defines a short DNA fragment in the proximal upstream region of the profilin P gene from which bidirectional replication is initiated. We further provide an estimate of the kinetics of elongation of the replicon and demonstrate that the 2 alleles of the profilin P gene are coordinately replicated. All these results were obtained on total DNA preparations extracted from untreated cells. They provide a strong evidence for site specific initiation of DNA replication in Physarum. PMID- 1630903 TI - Elk-1 protein domains required for direct and SRF-assisted DNA-binding. AB - The Ets-related Elk-1 protein can bind to purine-rich DNA target sites in a sequence specific fashion and, in addition, can form a ternary complex with the c fos serum response element (SRE) and the serum response factor (SRF). We demonstrate that Elk-1 can readily interchange between its different interaction partners. The amino terminal ETS-domain of Elk-1 was shown to be necessary and sufficient for direct DNA-binding activity. For ternary complex formation with the SRE and SRF, both the Elk-1 ETS-domain as well as flanking sequences up to amino acid 169 were required. Removal of sequences between the ETS-domain and amino acids 137-169 did not abolish ternary complex formation. This suggests the Elk-1 region spanning amino acids 137-169 to contain a protein-protein interaction domain. Furthermore, we have shown that a single amino acid exchange introduced into the ETS-domain can drastically alter the direct DNA-binding affinity of Elk-1 without severely affecting SRF-assisted binding to the SRE. Thus, Elk-1 requires different propensities of the ETS-domain to exert its different modes of DNA sequence recognition. PMID- 1630904 TI - Synthesis and properties of mirror-image DNA. AB - We have investigated the conformations of the hexadeoxyribonucleotide, L d(CGCGCG) composed of L-deoxyribose, the mirror image molecule of natural D deoxyribose. In this paper, we report the synthesis of four L-deoxynucleosides and the L-oligonucleotide-ethidium bromide interactions. The L-deoxyribose synthon 9 was synthesized from L-arabinose with an over all yield of 28.5% via the Barton-McCombie reaction. The L-deoxynucleosides were obtained by a glycosylation of appropriate nucleobase derivatives with the 1-chloro sugar 9. After derivatization to nucleoside phosphoramidites, L-deoxycytidine and L deoxyguanosine were incorporated into a hexadeoxynucleotide, L-d(CGCGCG) by a solid-phase beta-cyanoethylphosphoramidite method. This L-hexanucleotide was resistant to digestion with nuclease P1. The conformations of L-d(CGCGCG) were an exact mirror image of that of the corresponding natural one as described previously, and the conformations of the L-d(CGCGCG)-ethidium bromide complex were also the mirror images of those of the D-d(CGCGCG)-ethidium bromide complex under both low and high salt conditions. These results suggest that ethidium bromide prefers not a right-handed helical sense, but the base-base stacking geometry of the B-form rather than that of the Z-form. Thus, L-DNA would be a useful tool for studying DNA-drug interactions. PMID- 1630906 TI - Site-specific dissection of E. coli chromosome by lambda terminase. AB - We have succeeded the targeted cleavage of chromosomes by lambda terminase that introduces double-strand cleavages in DNA recognizing the lambda cos sequence. When chromosomal DNAs of various Escherichia coli K-12 strains were subjected to terminase digestion, all were found to contain two common cleavage sites. Therefore, DNAs from lambda lysogens in which lambda DNA was inserted at different chromosomal sites were specifically cleaved at one more additional site. The two sites, termed ecos1 and ecos2, were mapped at approximately 35.1' and 12.7' of E. coli genetic map. The ecos1 and ecos2 sites were included in qin and qsr' regions, respectively. Therefore, the cleavage sites were associated with cryptic prophages. Sequences at the ecos1 and ecos2 sites showed 98% homology to the lambda cos sequence, indicating high fidelity of sequence recognition by the terminase. Since the strategy for integration of a DNA segment into chromosomal DNA through homologous recombination has been established, the dissection method that uses lambda terminase should be applicable for gene mapping as well as construction of macrophysical maps of larger genomes. PMID- 1630905 TI - Nucleosomal histone protein protects DNA from iron-mediated damage. AB - Iron promotes DNA damage by catalyzing hydroxyl radical formation. We examined the effect of chromatin structure on DNA susceptibility to oxidant damage. Oxygen radicals generated by H2O2, ascorbate and iron-ADP (1:2 ratio of Fe2+:ADP) extensively and randomly fragmented protein-free DNA, with double-strand breaks demonstrable even at 1 microM iron. In contrast, polynucleosomes from chicken erythrocytes were converted to nucleosome-sized fragments by iron-ADP even up to 250 microM iron. Cleavage occurred only in bare areas where DNA is unassociated with histone. In confirmation, reassembly of nucleosomes from calf thymus DNA and chicken erythrocyte histone also yielded nucleosomes resistant to fragmentation. Protection of DNA by histone was dependent on nucleosome assembly and did not simply reflect presence of scavenging protein. In contrast to this specific cleavage of internucleosomal linker DNA by iron-ADP, iron-EDTA cleaved polynucleosomes indiscriminately at all sites. The hydroxyl radical scavenger thiourea completely inhibited the random cleavage of polynucleosomes by iron-EDTA but inhibited the nonrandom cleavage of polynucleosomes by iron-ADP less completely, suggesting the possibility that the lower affinity iron-ADP chelate may allow association of free iron with DNA. Thus, oxygen radicals generated by iron-ADP indiscriminately cleaved naked DNA but cleaved chromatin preferentially at internucleosomal bare linker sites, perhaps because of nonrandom iron binding by DNA. These findings suggest that the DNA-damaging effects of iron may be nonrandom, site-directed and modified by histone protein. PMID- 1630907 TI - Variants of the Xenopus laevis ribosomal transcription factor xUBF are developmentally regulated by differential splicing. AB - XUBF is a Xenopus ribosomal transcription factor of the HMG-box family which contains five tandemly disposed homologies to the HMG1 & 2 DNA binding domains. XUBF has been isolated as a protein doublet and two cDNAs encoding the two molecular weight variants have been characterised. The major two forms of xUBF identified differ by the presence or absence of a 22 amino acid segment lying between HMG-boxes 3 and 4. Here we show that the mRNAs for these two forms of xUBF are regulated during development and differentiation over a range of nearly 20 fold. By isolating two of the xUBF genes, it was possible to show that both encoded the variable 22 amino acid segment in exon 12. Oocyte splicing assays and the sequencing of PCR-generated cDNA fragments, demonstrated that the transcripts from one of these genes were differentially spliced in a developmentally regulated manner. Transcripts from the second gene were found to be predominantly or exclusively spliced to produce the lower molecular weight form of xUBF. Expression of a high molecular weight form from yet a third gene was also detected. Although the intron-exon structures of the Xenopus and mouse UBF genes were found to be essentially identical, the differential splicing of exon 8 found in mammals, was not detected in Xenopus. PMID- 1630909 TI - Homologous RNA recombination allows efficient introduction of site-specific mutations into the genome of coronavirus MHV-A59 via synthetic co-replicating RNAs. AB - We describe a novel strategy to site-specifically mutagenize the genome of an RNA virus by exploiting homologous RNA recombination between synthetic defective interfering (DI) RNA and the viral RNA. The construction of a full-length cDNA clone, pMIDI, of a DI RNA of coronavirus MHV strain A59 was reported previously (R.G. Van der Most, P.J. Bredenbeek, and W.J.M. Spaan (1991). J. Virol. 65, 3219 3226). RNA transcribed from this construct, is replicated efficiently in MHV infected cells. Marker mutations introduced in MIDI RNA were replaced by the wild type residues during replication. More importantly, however, these genetic markers were introduced into viral genome: even in the absence of positive selection MHV recombinants could be isolated. This finding provides new prospects for the study of coronavirus replication using recombinant DNA techniques. As a first application, we describe the rescue of the temperature sensitive mutant MHV Albany-4 using DI-directed mutagenesis. Possibilities and limitations of this strategy are discussed. PMID- 1630908 TI - Functional elements of the ribosomal protein L7a (rpL7a) gene promoter region and their conservation between mammals and birds. AB - The transcriptional initiation sites of the chicken ribosomal protein L7a (rpL7a) gene have been determined and found to occur at three consecutive cytidine residues at the start of a polypyrimidine tract of 8 base pairs (bp). A comparative analysis of the 5' upstream regions of the mouse, human and chicken rpL7a genes identified two sequence elements (Box A and Box B) conserved over the 600 million years of divergent evolution that separate mammals and birds. Only Box A (nts - 56 to - 39) and Box B (nts - 25 to - 4) sequences were detected to bind nuclear factors from mouse nuclear extracts in an analysis of the mouse rpL7a 5' upstream sequence. Box A and Box B bind different nuclear factors and the factor binding to mouse Box A and mouse Box B sequences could be effectively competed by corresponding homologous sequences from the human and chicken rpL7a promoters. These results indicate that elements of the rpL7a promoter region are conserved between mammals and birds. An in vivo analysis of the mouse rpL7a 5' upstream sequence required for efficient transcription identified the 5' border of the minimal promoter region as lying between nts - 50 and - 56. Constructs containing 56 bp of 5' upstream DNA and the first 25 bp rpL7a exon were very efficiently transcribed indicating that sequences within the first intron are not required for gene expression. No sequence similarity was detected between the rpL7a promoter elements and described promoter elements of other eukaryotic ribosomal protein genes. PMID- 1630910 TI - A comparison of the DNA bending activities of the DNA binding proteins CRP and TFIID. AB - Protein-induced DNA bending is of importance in the formation of complex nucleoprotein assemblies such as those involved in the initiation of DNA replication or transcription initiation. We have compared the DNA bending characteristics of the Escherichia coli cyclic AMP receptor protein (CRP or CAP), an archetypal DNA bending protein, to those of TFIID, the eukaryotic TATA-element binding transcription factor. By altering the helical phasing between a CRP binding site and the E. coli melR promoter we have mapped a DNA sequence-directed bend in the downstream region of the promoter. This intrinsic DNA bend may be important in the regulation of the melR promoter by CRP in vivo. Gel retardation assays and DNAse I footprinting show that human TFIID binds to the melR promoter 10 region. Taking advantage of this fact, and using the CRP-induced DNA bend as a standard, we have employed phase sensitive detection to show that the DNA bend angle induced by TFIID is far less than that induced by CRP. Further evidence to support this conclusion comes from a comparison of the relative mobilities of CRP DNA and TFIID-DNA complexes. These results place limits on the role of any DNA bending induced by TFIID alone in the initiation of transcription. PMID- 1630911 TI - Synthesis and properties of oligonucleotides containing aminodeoxythymidine units. AB - Procedures are described for synthesis via solid support methodology of oligonucleotide analogues derived in part from 3'-amino-3'-deoxythymidine or 5' amino-5'-deoxythymidine. Oligothymidylate decamers terminated with a 3'-amino group or containing a 3'-NHP(O)(O-)O-5' internucleoside link are found to form unusually stable complexes with poly(dA), poly(A), and oligo(dA). For related derivatives of 5'-amino-5'-deoxythymidine enhancement is less or absent, and in the case of multiple substitution destabilization of the heteroduplex may be observed. That the effect of the 3'-amino group is general for oligonucleotide derivatives is indicated by enhanced Tm values for heteroduplex complexes of the mixed-base oligomer, d(TATTCAGTCAT(NH2)), and the methyl phosphonate derivatives, TmTmTmTmTmTmTmTmTmT(NH2) and d(TmAmTmTmCmAmGmTmCmAmT(NH2)). PMID- 1630912 TI - Synthesis and physical properties of anti-HIV antisense oligonucleotides bearing terminal lipophilic groups. AB - A number of phosphoramidite monomers have been prepared and used in the synthesis of antisense phosphorothioate oligonucleotides bearing 5'-polyalkyl and cholesterol moieties. Similar groups have also been attached to the 3'-end of oligonucleotides by means of functionalised CPG. Melting temperatures of duplexes formed between phosphorothioate oligonucleotides with lipophilic end-groups and complementary DNA strands were found to be identical to those formed by the equivalent unmodified phosphorothioates. PMID- 1630913 TI - Construction of a human chromosome 4 YAC pool and analysis of artificial chromosome stability. AB - In order to construct a human chromosome 4-specific YAC library, we have utilized pYAC4 and a mouse/human hybrid cell line HA(4)A in which the only human chromosome present is chromosome 4. From this cell line, approximately 8Mb of chromosome 4 have been cloned. The library includes 65 human-specific clones that range in size from 30kb to 290kb, the average size being 108kb. In order to optimize the manipulation of YAC libraries, we have begun to investigate the stability of YACs containing human DNA in yeast cells; these studies will also determine if there are intrinsic differences in the properties of chromosomes containing higher eukaryotic DNAs. We are examining two kinds of stability: 1] mitotic stability, the ability of the YAC to replicate and segregate properly during mitosis, and 2] structural stability, the tendency of the YAC to rearrange. We have found that the majority of YACs examined are one to two orders of magnitude less stable than authentic yeast chromosomes. Interestingly, the largest YAC analyzed displayed a loss rate typical for natural yeast chromosomes. Our results also suggest that increasing the length of an artificial chromosome improves its mitotic stability. One YAC that showed a very high frequency of rearrangement by mitotic recombination proved to be a mouse/human chimera. In contrast to studies using total human DNA, the frequency of chimeras (i.e., mouse/human) in the YAC pool appeared to be low. PMID- 1630914 TI - Expression of wild-type and mutant p53 proteins by recombinant vaccinia viruses. AB - To facilitate the purification of wild type p53 protein, we established a recombinant p53 vaccinia viral expression system. Using this efficient eukaryotic expression vector, we found that the expressed p53 proteins retained their specific structural characteristics. A comparison between wild type and mutant p53 proteins showed the conservation of the typical subcellular localization and the expression of specific antigenic determinants. Furthermore, wild type p53 exhibited a typical binding with large T antigen, whereas no binding was detected with mutant p53. Both wild type and mutant p53 proteins were highly stable and constituted 5-7% of total protein expressed in the infected cells. These expression recombinant viruses offer a simple, valuable system for the purification of wild type and mutant p53 proteins that are expressed abundantly in eukaryotic cells. PMID- 1630915 TI - An experimental study of Saccharomyces cerevisiae U3 snRNA conformation in solution. AB - The conformation of Saccharomyces cerevisiae U3 snRNA (snR17A RNA) in solution was studied using enzymatic and chemical probes. In vitro synthesized and authentic snR17A RNAs have a similar conformation in solution. The S. cerevisiae U3 snRNA is folded in two distinct domains. The 5'-domain has a low degree of compactness; it is constituted of two stem-loop structures separated by a single stranded segment, which has recently been proposed to basepair with the 5'-ETS of pre-ribosomal RNA. We demonstrate that, as previously proposed, the 5'-terminal region of U3 snRNA has a different structure in higher and lower eukaryotes and that this may be related to pre-rRNA 5'-ETS evolution. The S. cerevisiae U3 snRNA 3'-domain has a cruciform secondary structure and a compact conformation resulting from an higher order structure involving the single-stranded segments at the center of the cross and the bottom parts of helices. Compared to tRNA, where long range interactions take place between terminal loops, this represents another kind of tertiary folding of RNA molecules that will deserve further investigation, especially since the implicated single-strands have highly evolutionarily conserved primary structures that are involved in snRNP protein binding. PMID- 1630916 TI - Insertion (sufB) in the anticodon loop or base substitution (sufC) in the anticodon stem of tRNA(Pro)2 from Salmonella typhimurium induces suppression of frameshift mutations. AB - The dominant +1 frameshift suppressors sufA6, sufB1 and sufB2, in Salmonella typhimurium act at runs of C and affect tRNA(Pro)1, tRNA(Pro)2 and tRNA(Pro)2, respectively. A recessive +1 frameshift suppressor, sufC, has a similar suppressor specificity (Riddle, D.L., and Roth, J.R., Mol. Biol. 66, 483 and 495, 1972). We show that sufC strains harbour two frameshift suppressors of which one, sufX201, is allelic to sufB. We cloned the sufB+ wild type allele and by recombination in vivo the mutations sufB1, sufB2 and sufX201. Determination of the DNA sequence revealed that the sufB1 and sufB2 mutations result in an extra G in the anticodon loop of the minor tRNA(Pro)2. The sufX201 mutation results in a base substitution (G43 to A43) in the anticodon stem of this tRNA. Although the sufB1 and sufB2 mutations were earlier shown to be dominant, the sufB+ wild type allele on multi copy plasmid inhibited the chromosomal sufB1, sufB2 and sufX201 mediated frameshift suppression but not that mediated by the dominant sufA6 mutation. These results are discussed in view of the possible coding specificity of these mutated tRNAs. The DNA sequence showed a potential consensus promoter sequence upstream of the structural gene for tRNA(Pro)2 and downstream a dyad symmetrical structure followed by a T cluster, a possible rho-independent termination signal. The Salmonella tRNA(Pro)2 gene is identical to the Escherichia coli counterpart reported by Komine, Y. et al. (J. Mol. Biol. 212, 579-598, 1990). While the 5' flanking sequence similarity between the two species is about 83%, the similarity of the 3' flanking sequence is only 42%. Still, the Salmonella tRNA(Pro)2 gene has a rho-independent transcriptional termination signal similar to the one present in E. coli tRNA(Pro)2 gene. PMID- 1630917 TI - Escherichia coli promoters: neural networks develop distinct descriptions in learning to search for promoters of different spacing classes. AB - Back-propagation neural networks were trained to recognize promoter sequences of each of the three major spacing classes found in E. coli. These networks were trained with the object of maximizing their ability to generalize while maintaining the level of false positive identifications at a fraction of 1 percent. These objectives were generally met. Networks for the 16 base spacing class captured between 78 and 100% of previously unseen promoters in different tests; networks for the 17 base class identified 97% of the test promoters; networks for the 18 base class identified 79% of the test promoters. A tandem poll of networks for all three spacing classes produced a cumulative false positive level of less than 0.5%. In each case, the weight matrices used by the networks in their classification were analyzed to determine the relative weight assigned to the occurrence of a given base at a given position within the promoter. In this fashion, an approximate description of the network's definition of the promoter can be obtained. PMID- 1630918 TI - A highly conserved repeated DNA element located in the chromosome of Streptococcus pneumoniae. AB - We report the discovery of a group of highly conserved DNA sequences located, in those cases studied, within intergenic regions of the chromosome of the Gram positive Streptococcus pneumoniae. The S. pneumoniae genome contains about 25 of these elements called BOX. From 5' to 3', BOX elements are composed of three subunits (boxA, boxB, and boxC) which are 59, 45 and 50 nucleotides long, respectively. BOX elements containing one, two and four copies of boxB have been observed; boxB alone was also detected in one instance. These elements are unrelated to the two most thoroughly documented families of repetitive DNA sequences present in the genomes of enterobacteria. BOX sequences have the potential to form stable stem-loop structures and one of these, at least, is transcribed. Most of these elements are located in the immediate vicinity of genes whose product has been implicated at some stage in the process of genetic transformation or in virulence of S. pneumoniae. This location raises the intriguing possibility that BOX sequences are regulatory elements shared by several coordinately controlled genes, including competence-specific and virulence-related genes. PMID- 1630919 TI - Analysis of DNA damage and repair in murine leukemia L1210 cells using a quantitative polymerase chain reaction assay. AB - The polymerase chain reaction (PCR) represents an alternative to the current methods for investigating DNA damage and repair in specific genomic segments. In theory, any DNA lesion which blocks Taq polymerase can be measured by this assay. We used quantitative PCR (QPCR) to determine the lesion frequencies produced by cisplatin and ultraviolet light (UV) in a 2.3 kilobase (kb) segment of mitochondrial DNA and a 2.6 kb segment of the DHFR gene in mouse leukemia L1210 cells. The frequency of UV-induced lesions increased linearly with dose, and was 0.58 lesions/10 kb/10 J/m2 in the mitochondrial DNA, and 0.37 lesions/10 kb/10 J/m2 in the DHFR gene. With cisplatin, the lesion frequency also increased linearly with dose, and was 0.17 lesions/10 kb/10 microM in the DHFR gene, and 0.07 lesions/10 kb/10 microM in mitochondrial DNA. This result is contrary to that of Murata et al., 1990 (1), in which mitochondrial DNA received greater cisplatin damage than did nuclear DNA. Using PCR to measure the repair of UV induced lesions in the DHFR gene segment, we observed that less than 10% of the lesions were removed by 4 h, but over 70% of the lesions were removed by 8 h. Repair of 43% of UV-induced lesions in mitochondrial DNA was also observed during a 24 h period. PMID- 1630920 TI - A negative regulating element controlling transcription of the gene encoding acyl CoA oxidase in Saccharomyces cerevisiae. AB - Peroxisomes are induced in Saccharomyces cerevisiae when this yeast is grown in the presence of oleate, and are repressed when glucose is supplied as the carbon source. Concomitant with this is an induction/repression of peroxisomal beta oxidation enzymes. We are investigating the transcriptional control of acyl-CoA oxidase, the first and rate-limiting enzyme in the peroxisomal beta-oxidation cycle. The promoter region of POX1 from S. cerevisiae has been analyzed in POX1/lacZ fusions. Expression of the POX1/lacZ fusion protein underwent glucose repression and oleate induction. By deletion, DNA band shift and DNase I footprinting analyses we have identified a region that is involved in transcriptional repression of POX1. Elimination of this DNA sequence results in constitutive expression of POX1 when S. cerevisiae is grown on a fermentable carbon source or glycerol. PMID- 1630921 TI - Nucleotide sequence of transfer RNA genes from the linear mitochondrial DNA of the yeast Williopsis mrakii and Pichia pijperi. PMID- 1630922 TI - Nucleotide sequence of genes for a 5.8S and 25S rRNA from rape seed (Brassica napus). PMID- 1630923 TI - Nucleotide sequence of trnI(CAU) and rpl23 from Arabidopsis thaliana chloroplast genome. PMID- 1630924 TI - Complete nucleotide sequence of a hepatitis E virus isolated from the Xinjiang epidemic (1986-1988) of China. PMID- 1630925 TI - ApaCI, an isoschizomer of BamHI isolated from Acetobacter pasteurianus. PMID- 1630926 TI - Nucleotide sequence of tryptophan tRNA from Bacillus subtilis. PMID- 1630927 TI - Cloning and sequencing of the 3' half of a potato virus Y (O strain) genome encoding the 5k protein, protease, polymerase and coat protein. PMID- 1630928 TI - Nucleotide sequence of a mouse cDNA encoding the nonhistone chromosomal high mobility group protein-1 (HMG1). PMID- 1630929 TI - Sequence of a new snRNA from the ciliate Tetrahymena thermophila. PMID- 1630930 TI - Nucleotide sequence of a mouse testis poly(A) binding protein cDNA. PMID- 1630931 TI - Prediction of oligodeoxyribonucleotides eluting salt conditions on anion exchange column. PMID- 1630932 TI - Basic peptides enhance protein/DNA interaction in vitro. PMID- 1630933 TI - Triplex affinity capture of a single copy clone from a yeast genomic library. PMID- 1630934 TI - A high-capacity column for affinity purification of sequence-specific DNA-binding proteins. PMID- 1630936 TI - A procedure to standardize CAT reporter gene assay. PMID- 1630935 TI - Transient expression of DNA in Drosophila via electroporation. PMID- 1630937 TI - A novel method for the isolation of tissue-specific genes. PMID- 1630938 TI - Preparation of nested deletions in single-strand DNA using oligonucleotides containing partially random base sequences. PMID- 1630940 TI - cDNA sequence of rabbit tissue factor pathway inhibitor. PMID- 1630941 TI - Mentor's cold shoulder left Project 2000 student demoralised. PMID- 1630939 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1630942 TI - Women's voices. PMID- 1630943 TI - Taking positive action. PMID- 1630945 TI - Midwifery support? PMID- 1630944 TI - Remember the children. PMID- 1630946 TI - Complementary care. PMID- 1630947 TI - Providing a source of support. PMID- 1630948 TI - Action for health. PMID- 1630950 TI - Management--changing times. PMID- 1630949 TI - A helpful assessment. PMID- 1630951 TI - A belated diagnosis. Interview by Ian McMillan. PMID- 1630952 TI - Taking pains. PMID- 1630953 TI - A test of ethics. PMID- 1630954 TI - Package deals. Learning disabilities. PMID- 1630955 TI - Health promotion by numbers. PMID- 1630956 TI - Aboriginal adventure. PMID- 1630957 TI - Community care for the dying. PMID- 1630958 TI - Understanding nursing audit. PMID- 1630959 TI - Springing the poverty trap. RCM supplement. PMID- 1630960 TI - Opening the gates? RCM supplement. PMID- 1630961 TI - Paying the piper. RCM supplement. PMID- 1630962 TI - Who can speak for women? RCM supplement. PMID- 1630963 TI - View from the top. RCM supplement. Interview by Jane Seymour. PMID- 1630964 TI - Physeal injuries of the distal humerus. AB - Physeal injuries of the distal humerus comprise approximately 10% of all physeal injuries. Diagnosis of these injuries at a young age before the ossification centers have ossified and become visible radiographically is difficult. Poor outcome of distal humeral physeal injuries is not uncommon and can be best prevented by knowledge of anatomy and the use of all appropriate imaging techniques. The focus of this article is to correlate anatomy at different ages with the occurrence of specific injuries. PMID- 1630965 TI - Supracondylar fractures of the humerus in children. AB - Supracondylar fractures of the humerus in children are either flexion or extension in type. Associated nerve or vascular injury is common. Fractures that remain stable after reduction can be treated with elbow flexion. If the fracture is unstable or if circulation is compromised, percutaneous pinning or traction treatment is utilized. The ischemic hand is always evaluated for brachial artery damage or for the presence of a compartment syndrome. Varus positioning should always be avoided, but other malalignments either remodel or are not of functional significance. PMID- 1630966 TI - Fractures of the distal humerus. AB - We present a rational approach to the classification and surgical management of intraarticular fractures of the distal humerus. The fractures are classified on the basis of the surgical anatomy of the distal humerus, which is divided into two skeletal columns held together by the trochlea. The basic surgical aim is to restore all three elements with sufficient stability to permit functional movement. The surgical tactics are presented in detail. PMID- 1630967 TI - Indications and technique of open reduction and internal fixation of radial head fractures. PMID- 1630969 TI - Elbow arthroscopy for loose bodies. AB - Arthroscopy is highly useful for the diagnosis and treatment of loose bodies of the elbow. Not all loose bodies are detected radiographically, and often there are multiple loose bodies, sometimes both anteriorly and posteriorly. When not complicated by an underlying disorder such as arthritis, loose bodies can be removed from any part of the elbow to provide excellent results in a predictable manner. This article describes techniques developed for the safe and effective application of this procedure in the elbow. PMID- 1630968 TI - Classification and treatment of coronoid process fractures. AB - Fractures of the coronoid process are rare as isolated injuries and usually are associated with significant, sometimes devastating trauma to the elbow. The classification system based on the degree of involvement has proven helpful to estimate prognosis and to help guide treatment. Severe fractures are generally associated with instability and portend a poor prognosis. Treatment by distraction, external fixation, and early motion has been encouraging. PMID- 1630970 TI - Posttraumatic stiffness: distraction arthroplasty. AB - Loss of motion after elbow trauma is a common complication. At times, the limitation of motion may significantly impair function. Options to improve posttraumatic motion by surgery depend on whether the joint surface has been severely involved (intrinsic vs extrinsic contracture). Increasing experience with the surgical release of the posttraumatic stiff elbow has been enhanced by the use of distraction with or without interposition arthroplasty. Current experience suggests that approximately 85% of patients will be satisfactorily treated with surgical intervention. PMID- 1630971 TI - Radial head fracture associated with elbow dislocation. PMID- 1630972 TI - The role of tracheostomy in the adult intensive care unit. PMID- 1630973 TI - Diuretic-induced hypokalaemia and surgery: much ado about nothing? PMID- 1630974 TI - Thrombocytopenia in pregnancy. PMID- 1630975 TI - Recent advances in cardiology. PMID- 1630976 TI - Experience with tracheostomy in medical intensive care patients. AB - Thirty-four intensive care patients who received elective tracheostomies were studied to determine the incidence and nature of complications associated with tracheostomies. Indication for tracheostomy was long-term ventilation. Adverse consequences occurred in 47% of the patients. The most frequent problem was pneumonia. There were no intraoperative complications. Two deaths occurred due to delayed haemorrhage. Some complications of tracheostomy were influenced by the preceding period of endotracheal intubation. In patients requiring prolonged mechanical ventilation, tracheostomy carries a considerable risk. Optimal airway care only will reduce the incidence of complications. PMID- 1630977 TI - Metastatic cervical lymph nodes: general practitioner referral patterns. AB - Premature excision biopsy of a cervical lymph node infiltrated by metastatic carcinoma may compromise patient survival since it is associated with an increased incidence of local wound recurrence and distant metastases. Seventy per cent of such patients have an identifiable head and neck primary, obviating the need for an excision biopsy. It is important therefore that they are examined by surgeons who are experienced in inspecting the upper aerodigestive tract and who are competent in performing definitive head and neck surgery. A questionnaire sent to all general practitioners of an Inner London and a District Health Authority revealed that only 18% and 33% respectively referred patients who they suspected of having a metastatic neck node to a department with an experienced head and neck surgeon. We conclude that greater emphasis on the correct management of these patients at both an undergraduate and postgraduate level may encourage subsequent generations of general practitioners to review their referral patterns. PMID- 1630978 TI - Extended transduodenal sphincteroplasty for bile duct stones associated with a periampullary diverticulum. AB - Extended transduodenal sphincteroplasty has been suggested as an alternative to choledochoduodenostomy for the surgical management of bile duct stones associated with a periampullary diverticulum but its value has not previously been investigated. Over a 3 year period, nine patients underwent extended transduodenal sphincteroplasty for common bile duct calculi associated with a periampullary diverticulum with no operative or post-operative mortality and minimal morbidity. Follow-up ranging from 20 to 60 months has shown remission of pain in all but one patient, who has had a normal endoscopic cholangiogram and no further episodes of jaundice or cholangitis. Extended transduodenal sphincteroplasty is a safe and effective alternative to choledochoduodenostomy for the surgical management of choledocholithiasis associated with a periampullary diverticulum. PMID- 1630979 TI - 'The Health of the Nation': the impact of personality disorder on 'key areas'. AB - The purpose of this response paper is to document a form of mental illness, namely, personality disorder: (1) whose impact is far-reaching, impinging on different 'key areas' identified in 'The Health of the Nation' (The Health of the Nation: A Consultative Document. HMSO, London, 1991), including: eating and drinking habits, smoking, prevention of accidents, human immunodeficiency (HIV)/acquired immunodeficiency syndrome (AIDS), and other mental illness itself; (2) which tends to be underdiagnosed by health-care professionals in spite of its aetiological relationship to other 'key areas' (as above); (3) which tends to be associated with negative therapeutic attitude in spite of well-documented, albeit specialist, treatment expertise; (4) which, importantly, transmits psychopathology from one generation to the next and hence has a pivotal role to play in prevention; and (5) which, for the reasons enumerated above, could form a 'target' for various, measurable, interventions. PMID- 1630981 TI - Recurrent intra-cranial granulomata presenting as space-occupying lesions in a patient with common variable immunodeficiency. AB - A patient with profound panhypogammaglobulinaemia due to common variable immunodeficiency developed two discrete intra-cranial space-occupying lesions, 10 years apart, requiring craniotomy. Histological examination revealed the intra cranial masses to be granulomata of unknown aetiology on both occasions. PMID- 1630980 TI - Colonoscopy in patients aged 80 years or older and its contribution to the evaluation of rectal bleeding. AB - Colonoscopies performed in patients aged 80 years or older at the Sheba Medical Center were analysed according to the primary indication for the procedure: 101 colonoscopies were performed because of rectal bleeding of at least 2 months duration, and 335 for all other indications. Carcinoma of the large bowel was found in 29 (28.7%) bleeders, with the rectum being the most frequently involved site (12 patients). Among the non-bleeders, the prevalence of cancer was significantly lower (33 cases, 9.8%; P less than 0.001), and rectal carcinoma was less common (five patients, P = 0.04), but proximal tumours were more frequent. Of patients with cancer who had operations, the majority (72%) had a tumour confined to the bowel wall (Dukes A or B). The rate of adenomas was similar for both groups (34% vs 29%). The non-bleeders complained more frequently of abdominal pain or a change in bowel habits as compared to the bleeders, but both groups had similar rates for anaemia and weight loss. In all, 47% of these octogenarians with cancer, and 26% with adenomas were referred for colonoscopy because of rectal bleeding. This procedure was found to be safe in old age, as we recorded only four (0.9%) non-fatal complications among our series, a similar figure to the overall incidence of complications at our Institute. In conclusion, our data indicate that rectal bleeding in octogenarians warrants a complete colonic investigation, preferably by total colonoscopy. PMID- 1630982 TI - Blastomycosis-like pyoderma in a case of chronic myeloid leukaemia. AB - Blastomycosis-like pyoderma, a rare skin lesion which may clinically resemble true blastomycosis, is seen in immuno-compromised individuals. We report one such case in chronic myeloid leukaemia. PMID- 1630983 TI - Lymphomatoid granulomatosis presenting as angioedema. AB - We describe a patient with severe eyelid and lip angioedema lesions in whom biopsy specimens from angioedematous labial mucosa disclosed features of lymphomatoid granulomatosis. To our knowledge, angioedema lesions with characteristic histological findings of lymphomatoid granulomatosis have not been previously described as a presenting sign of this disease. PMID- 1630984 TI - 'Chest epilepsy' in a child. AB - Pain is a most unusual manifestation of epilepsy, and it is rarer still for chest pain to be the primary manifestation of a seizure disorder. We report here a 6 year old boy with epileptic chest pain--'chest epilepsy'--an entity not previously described in children. PMID- 1630986 TI - Guillain-Barre syndrome in Plasmodium falciparum malaria. AB - A patient with Plasmodium falciparum malaria developed peripheral neuropathy. Clinical, cerebro-spinal fluid examination and nerve conduction studies confirmed Guillain-Barre syndrome, not previously reported in P. falciparum malaria. PMID- 1630985 TI - Lipid and lipoprotein metabolism in familial combined hyperlipidaemia during treatment of sporadic phaeochromocytoma: a case study. AB - Lipid metabolism was evaluated during management of phaeochromocytoma in a 41 year old non-obese post-menopausal women with familial combined hyperlipidaemia. The main effect of the excess catecholamine secretion on lipid metabolism was increased lipolytic activity, lower serum triglyceride and increased HDL cholesterol concentrations, compared with findings following removal of the tumour. Before removal of the tumour, the use of beta blockers alone led to marked deterioration of the hyperlipidaemic state, and combined alpha and beta blockade additionally led to a marked reduction in fat oxidation and lipoprotein lipase activity. Overactivity of the adrenergic system leads to changes in lipid metabolism in phaeochromocytoma. Treatment of the phaeochromocytoma may lead to worsening of hyperlipidaemia pre-existing in such individuals. PMID- 1630987 TI - Congenital left ventricular diverticula: a rare cause of sudden cardiac death. AB - Congenital left ventricular diverticula are a rare cause of sudden cardiac death. We describe the first reported case of ventricular fibrillation in association with congenital diverticula of the heart. The diagnosis of left ventricular diverticula was made by cardiac catheterization and confirmed by magnetic resonance imaging. Treatment was initiated with anti-arrhythmic and anticoagulant drugs to prevent life-threatening arrhythmias and emboli. PMID- 1630988 TI - A case of polycythaemia vera presenting with intramuscular chest wall haematoma. AB - A 40 year old male, previously well, presented with a posterior chest wall haematoma. Computerized tomography and ultrasound showed this to be intramuscular. Haematological indices were consistent with a diagnosis of polycythaemia vera. The haematoma and indices responded to hydroxyurea and venesection. This rare presentation of polycythaemia vera in a young person is described and the haemorrhagic complications of polycythaemia vera discussed. PMID- 1630989 TI - Primary pulmonary hypertension and functional hyposplenism. AB - Primary pulmonary hypertension is a rare disease of unknown case. Functional hyposplenism is characterized by the appearance of abnormal circulating erythrocytes despite the presence of a spleen and is associated with a variety of disease states. A case of primary pulmonary hypertension associated with functional hyposplenism is described in this report. PMID- 1630990 TI - Graves' disease and insulin-dependent diabetes mellitus in idiopathic Addison's disease. PMID- 1630991 TI - Pneumoperitoneum without peritonitis. PMID- 1630992 TI - Changes in pulmonary function in systemic sclerosis. PMID- 1630993 TI - Third degree heart block in acromegaly. PMID- 1630994 TI - Masked faecal peritonitis in Cushing's syndrome. PMID- 1630995 TI - Trimethoprim-induced vasculitis. PMID- 1630996 TI - Listeria rhombencephalitis in a previously healthy adult. PMID- 1630997 TI - Membranous nephropathy associated with diclofenac. PMID- 1630998 TI - Thrombotic thrombocytopenic purpura due to Mycoplasma pneumoniae. PMID- 1630999 TI - Amiodarone-induced thyrotoxicosis responding to oral steroid therapy. PMID- 1631000 TI - Idiopathic thrombocytopenic purpura and acute polyneuritis: a coincidence or association? PMID- 1631001 TI - Early diagnosis of colorectal cancer. PMID- 1631002 TI - A patient's request to change GPs. PMID- 1631003 TI - Cervical cancer. PMID- 1631004 TI - Re-infection and congenital rubella syndrome. PMID- 1631005 TI - Negative symptoms of schizophrenia. PMID- 1631006 TI - Work, health and disease. PMID- 1631007 TI - Transplantation update. PMID- 1631008 TI - Childhood bone marrow transplantation. PMID- 1631009 TI - The oral examinations. PMID- 1631010 TI - Rethinking antenatal care. PMID- 1631011 TI - Women's concerns. PMID- 1631012 TI - Antenatal diagnosis. PMID- 1631013 TI - Childbirth and mental health. PMID- 1631015 TI - Oral NSAIDs: the best choice in practice. PMID- 1631014 TI - Breastfeeding: the GP's role. PMID- 1631016 TI - Control of melanocyte proliferation and differentiation in the mouse epidermis. AB - Melanocyte-stimulating hormone plays an important role in the regulation of melanocyte differentiation in the mouse epidermis by inducing tyrosinase activity, melanosome formation, translocation of melanosomes, and increased dendritogenesis. The proliferative activity of differentiating epidermal melanocytes of newborn mice during the healing of skin wounds is regulated by semi-dominant genes, suggesting that the genes are involved in regulating the proliferative activity of epidermal melanocytes during differentiation. From the results of serum-free culture of epidermal cell suspensions from neonatal mouse skin, basic fibroblast growth factor is shown to stimulate the sustained proliferation of melanoblasts in the presence of dibutyryl adenosine 3',5'-cyclic monophosphate and keratinocyte-derived factors. Moreover, each step of melanocyte differentiation is controlled by numerous coat color genes. These genes control melanocyte differentiation by regulating the differentiation of neural crest cells into melanoblasts in embryonic skin, or by regulating the differentiation of neural crest cells into melanoblasts in embryonic skin, or by regulating transcription and/or translation of the tyrosinase gene in the differentiating melanocytes. These results suggest that melanocyte proliferation and differentiation in the mouse epidermis are controlled by both genetic factors and local tissue environment. PMID- 1631018 TI - Response of transformed and normal mouse cell lines to anti-melanin compounds, hyperthermia, and radiation. AB - Five cell lines (one parental, two transformed melanin producing, and two transformed non-melanin producing) were evaluated for the responses to 2- and 4 hydroxyanisole (2HA, 4HA) alone or combined with hyperthermia or radiation. All cells exhibited a non-specific toxic response to the two compounds and the effect was exposure time and concentration dependent and was greater for 4HA compared to 2HA. In addition, the two melanin-producing cell lines were more sensitive, demonstrating specific toxicity to such cell lines. The treatment with either 2HA or 4HA combined with heat and radiation resulted mostly in additive or antagonistic effects, except for one combination of 2HA plus radiation in the melanin-producing R25 cells. Thus, while these compounds may be useful in therapy for pigmented melanomas, combined treatment with radiation is not recommended. PMID- 1631017 TI - Differentiation of new metastatic variants of B16 melanoma under different culture conditions. AB - The purpose of this study was to examine the differentiation of variant tumors of the B16 metastatic melanoma when tumors were grown serially under different culture conditions and transplanted into C57BL/6J black mice, lethal yellow Ay/a, albino c/c, and C+/c mutant mice. Morphological and biochemical markers of melanogenesis were examined in cells in culture and in the corresponding tumors. Cellular pigmentation was assessed in terms of the levels of DOPA and 5-S-CD and in terms of tyrosinase activity in the various cell lines and tumors. The observed change from high to low metastatic capacity, which was dependent on culture conditions, appeared to be unrelated to melanogenesis even though changes were observed in the biochemical melanotic phenotype. Overall, tumor cells from spontaneous pulmonary metastases appear to differentiate in ways that are unrelated to the instability of experimental metastatic capacity. The melanotic phenotype in albino c/c and C+/c mice was dependent on the phenotype of the parental tumors. A marked difference was observed between two pigmentation compartments, one of which was stable in the B16 control, while the other was unstable in YB16 and MB16 variant cells and in the tumors derived from them. It appears, therefore, that the metastatic capacity of B16 metastatic variants is changeable and is independent of the unstable melanogenic behavior. The production of metastases and the differentiation of tumors in the present experiments appeared to be related to the genetic background of the mice and the epigenetic metabolic environment of tumors and cells. PMID- 1631019 TI - Hyperpigmentation of chinchilla stria vascularis following acoustic trauma. AB - This report describes morphological alterations of the chinchilla stria vascularis seen 30 days after exposure to impulse noise. The observed changes included a dramatic increase in strial melanin content which occurred in 7 of 36 animals exposed to electronically synthesized impluses presented in various temporal patterns at either 135 or 150 dB peak SPL. In these animals, densely pigmented areas of stria 1.5 to 3 mm in length were found in the basal cochlear turn. Light and electron microscopic study revealed that these areas contained large numbers of melanin granules situated primarily in pale-staining cells of the middle layer of the stria. Unlike the pigment granules present in normal chinchilla stria, the melanosomes found in the noise-exposed material clearly showed ultrastructural features characteristic of eumelanin. Melanin granules were also observed in marginal and basal cells of the noise-exposed stria. In some cases, pigment granules which had apparently been expelled from the marginal cells were present in the endolymphatic space beneath Reissner's membrane and on the strial surface. These findings support the view that the melanin-bearing cells of the inner ear are capable of markedly increased activity in response to stressful conditions. PMID- 1631020 TI - Tissue distribution of para-boronophenylalanine administered orally as a cyclodextrin inclusion complex to melanoma-bearing hamsters. PMID- 1631021 TI - Synergism exerted by 4-methyl catechol, catechol, and their respective quinones on the rate of DL-DOPA oxidation by mushroom tyrosinase. AB - 4-Methyl catechol and catechol, at concentrations ranging from 0.03 to 9 mM and 0.066 to 20 mM, respectively, have a synergistic effect on the rate of DL-DOPA oxidation by mushroom tyrosinase to material absorbing at 475 nm. The synergism results from the ability of 4-methyl catechol-o-quinone (4-methyl-o-benzoquinone) and of catechol-o-quinone (o-benzoquinone) to oxidize DL-DOPA non-enzymatically to dopaquinone, with the later being immediately converted to dopachrome (lambda max = 475 nm). PMID- 1631022 TI - Does the introduction of a new player, the endoplasmic reticulum, create more or less confusion in understanding the mechanism(s) of pigmentary organelle translocations? AB - In 1925, Wilson listed, in his classic third edition of Cell in Development and Heredity, four theories for the morphological and physiological characteristics of cytoplasm; each theory provided some sort of explanation as to the mechanism(s) of organelle translocations. During the past twenty years, cell biologists have focused their attentions on the cell's cytoskeleton, microtrabecular lattice, and associated mechanochemical motors which drive organelles along cytoskeletal tracks. A number of cell types have been used to study organelle translocations, but chromatophores, pigment cells, from cold blooded vertebrates have been one of the more popular models. This article reviews some of the research findings during the past twenty years, particularly those involving cytoplasmic elements: i.e, microfilaments, intermediate filaments, microtubules, and mechanochemical motors. In addition, it contrasts the proposed involvement of these elements in organelle translocations with the endoplasmic reticulum, a tubulovesicular organelle, which we recently demonstrated is responsible, through its elongation or retraction, for the translocations of carotenoid droplets in goldfish xanthophores and swordtail fish erythrophores. Here, the carotenoid droplets are not free in the cytoplasm and do not translocate via cytoskeletal tracks, but instead are attached to or are a part of the endoplasmic reticulum. On the other hand, carotenoid droplets of squirrel fish erythrophores are free in the cytoplasm and appear to translocate via microtubules. Finally, the rates of pigmentary organelle translocations are reviewed in light of the participation of the cytoskeletal elements with the endoplasmic reticulum. PMID- 1631023 TI - Effect of different isomers of dihydroxybenzoic acids (DBA) on the rate of DL dopa oxidation by mushroom tyrosinase. AB - Dihydroxybenzoic acids (DBA), such as 3,4-DBA, 3,5-DBA, and 2,4-DBA--at all concentrations tested--inhibited the rate of DL-DOPA oxidation to dopachrome (lambda max = 475 nm) by mushroom tyro0sinase. 2,3-DBA and 2,5-DBA at relatively low concentration had a synergistic effect on the reaction, whereas at relatively high concentrations they inhibited the rate of DL-DOPA oxidation. The synergistic effect of 0.6-13.3 mM 2,3-DBA on the rate of DL-DOPA oxidation to dopachrome (lambda max = 475 nm) was found to be due to the ability of 2,3-DBA-o-quinone (formed by the oxidation of 2,3-DBA by mushroom tyrosinase or by sodium periodate) to oxidize DL-DOPA to dopachrome (via dopaquinone) non-enzymatically. A similar explanation is likely to be valid for the synergism exerted by 2,5-DBA on the rate of DL-DOPA oxidation by mushroom tyrosinase. PMID- 1631024 TI - Current topic: the synepitheliochorial placenta of ruminants: binucleate cell fusions and hormone production. PMID- 1631025 TI - Current topic: midgestation cord sampling: what have we learned. PMID- 1631026 TI - Antibodies to hCG inhibit progesterone production from human syncytiotrophoblast cells. PMID- 1631027 TI - Protein turnover in rat placenta: effects of maternal fasting and maternal protein restriction. AB - Biochemical composition and variables of protein turnover were determined in rat placenta at 21 days gestation in control animals and in animals subjected to 72-h fasting and protein/calorie restriction (6 per cent protein) throughout gestation. Placental protein synthesis was determined following the injection of 'massive' amounts of 14C-phenylalanine intravenously to the pregnant rat. Protein content was reduced in placentas from rats that were fasted for 72 h and in those who were protein restricted throughout pregnancy. Placental RNA content was significantly reduced only in the protein-restricted animals. Fractional rates of protein synthesis were reduced in placentas from the protein-restricted animals (Ks = 17.9 +/- 0.8 per cent per day in controls versus 11.7 +/- 0.9 in protein restricted, P = 0.002), but not in fasted animals. Fractional protein breakdown was markedly enhanced in placentas following maternal fasting (Kd = 9.9 per cent per day in controls versus 26.0 per cent in fasted), but not affected by protein deprivation. These results mimic those previously reported for other fetal tissues under these experimental conditions. PMID- 1631028 TI - Uptake of zinc by human placental microvillus border membranes and characterization of the effects of cadmium on this process. AB - The uptake of Zinc (Zn) by microvillus border membrane vesicles formed from the trophoblast of term human placentae is markedly increased over brief periods of incubation with much slower increases persisting for up to 2 h of incubation. Zinc is both bound to membrane components and transported into intravesicular osmotically active space. Uptake is saturable, temperature dependent from 4 to 37 degrees C with a Q10 of 1.7, and is inhibited by the sulphydryl agent DTNB. About 20 per cent of the uptake is susceptible to inhibition by Cadmium (Cd) at concentrations from 5 to 50 microM, a significant part of the action of this metal being on the transmembrane component of Zn uptake. PMID- 1631029 TI - A fibrin matrix modulates the proliferation, hormone secretion and morphologic differentiation of cultured human placental trophoblast. AB - Term placental trophoblast epithelialize fibrin deposits attached to villi in vitro and trophoblast cultured on a fibrin matrix form an epithelial bilayer typical of the trophoblast layer on term villi. We compared the morphology of cells grown on fibrin with cells grown on substrates of type IV collagen, laminin, type I collagen, or Matrigel. We also used autoradiography, hormone assays, electron microscopy, and immunofluorescence to determine what functional activities were influenced by trophoblast-fibrin interactions. Cultured cellular trophoblast from term placentae differentiated to form syncytial trophoblast and to secrete estrogen, progesterone, and hCG in the presence or absence of matrices. Trophoblast proliferation was lower in cells grown on matrices and was inversely related to cell height after 24 h in culture. Cells grown on fibrin remained the tallest and had the lowest labelling index. Cells grown for 72 h on fibrin had the most dilated rough endoplasmic reticulum but the lowest media hormone levels. Only cells grown on a fibrin matrix formed a basal lamina-like structure at the trophoblast-substrate interface, and only a fibrin matrix facilitated trophoblast to form an epithelial bilayer in culture. However, this histology was not accompanied by a change in the amount of syncytial trophoblast formed by the cells grown on fibrin. The results suggest that a fibrin matrix uniquely modulates the trophoblast phenotype, away from the secretion of placental specific products like hCG in favour of a repair-oriented phenotype that forms basement membrane and a trophoblast bilayer. PMID- 1631030 TI - Characterization of human placental activity for transport of L-alanine, using brush border (microvillous) membrane vesicles. AB - To characterize the placental activity for the transport of amino acids, the uptake of L-alanine was investigated by rapid membrane filtration using brush border membrane vesicles separated from the human placenta of early pregnant (12 13 gestational weeks) and late pregnant (37-38 gestational weeks) women. The uptake of L-alanine into the brush border membrane vesicles at early and late stage of gestation showed a pattern of transport dependent on the intra- and extravesicular Na+ concentration gradient (extravesicular Na+ greater than intravesicular Na+). The Na+ concentration gradient-dependent uptake of L-alanine into the brush border membrane vesicles at early and late stage of gestation also showed a dependency on the potential difference of the internal and external membrane. The transport of L-alanine into the brush border membrane vesicles was markedly augmented at late stage of gestation. On the basis of the double reciprocal plotting of the L-alanine concentration and the Na(+)-dependent uptake of L-alanine into the vesicles, Km and Vmax were calculated as parameters of the Na(+)-dependent uptake of L-alanine into the vesicles. In the early stage of gestation Km was 0.78 mM, and in the late stage of gestation was 0.80 mM. In the early stage of gestation Vmax (nmol/mg protein/20 sec) was 0.62, and in the late stage of gestation was 3.53. From the results, it was considered that the placental active transport mechanism of L-alanine is the same in the early and late stages of gestation, and it was shown that its transport activity increases greatly in late stages compared to the early stages of gestation. PMID- 1631031 TI - Classics revisited: Otto Grosser's monographs. PMID- 1631032 TI - Levels of placental protein 14, human placental lactogen and unconjugated oestriol in extraembryonic coelomic fluid. PMID- 1631033 TI - [Interstitial Lung Diseases. 22nd Scientific Meeting of the North German Association of Pulmonary and Bronchial Medicine. Berlin, 3-5 October 1991. Abstracts]. PMID- 1631034 TI - The evolution of health promotion. AB - This paper describes the evolution of health promotion from its nascent roots which focused upon lifestyle to its global concepts of managing the future. A lifestyle orientation was the focus of approximately the first decade of health promotion efforts which followed the release of the 1974 document, "A New Perspective on the Health of Canadians". This was also a period of national health goal setting in Europe and in the United States. In 1984, the World Health Organization defined health promotion as the process of enabling individuals to take control over and to maintain their health. The focus of health promotion efforts thus changed from an emphasis on the individual to the more structural factors in society which support the types of choices that people ultimately make. Achieving Health for All: A Framework for Health Promotion, released in November 1986, further developed the concept of health promotion, suggesting three strategies for increasing health promotion: fostering public participation, strengthening community health services and healthy public policy. The health promotion movement has had other spin-offs such as the "Healthy Cities Movement" which was begun by another Canadian, Trevor Hancock. The newest evolution of the health promotion movement is a concern for a Healthy Future. PMID- 1631035 TI - Health promotion workshop. PMID- 1631036 TI - Public health programs. PMID- 1631037 TI - A multidisciplinary approach to health promotion for seniors. PMID- 1631038 TI - Canadian students in U.S. dental hygiene programs. PMID- 1631039 TI - Studies on chimeric fusion proteins of human aldolase isozymes A and B. AB - Several kinds of fusion proteins between human aldolases A and B were prepared by recombinant DNA technology and their enzymic properties were examined. AB chimeras, which have aldolase A at the N-terminal region and aldolase B at the C terminal region, were scarcely obtained, while BA chimeras were abundant (Kitajima et al., (1990), J. Biol. Chem., 265, 17493-17498). All the BAB chimeras, aldolase A fragments inserted in aldolase B, showed activity assignable to aldolase B type, which imply an essential role of Tyr residue at the C terminus of aldolase A in the binding of fructose-1,6-bisphosphate (Fru-1,6-P2). BAB chimeras also showed reactivity to effectors such as fructose-2,6 bisphosphate (Fru-2,6-P2) and pyridoxal 5-phosphate (PLP), in a similar manner to aldolase B. BAB108 has a similarity to the BA108 chimera, but acts differently from other BAB chimeras, suggesting that its structure around active site looks like that of aldolase A. PMID- 1631040 TI - Uncoupling of catalysis and colipase binding in pancreatic lipase by limited proteolysis. AB - In the intestine, the hydrolysis of triglycerides by pancreatic lipase is performed only in the presence of colipase, whose function is to anchor lipase to the bile-salt-coated lipid interface. Biochemical and crystallographic data on porcine and human lipases have shown that the molecule is made of two well delimited domains. In order to get more information on the role of the domains in catalysis and colipase binding, we performed limited proteolysis on lipase from various species and obtained different patterns of cleavage. In the case of porcine and human lipases, only the C-terminal domain (12 kDa) could be obtained after chymotryptic attack, whereas in the horse enzyme the cleavage of the Leu410 Thr411 bond gave rise to a large N-terminal (45 kDa) and a small C-terminal (4 kDa) fragment. The isolated porcine and human C-terminal domains were completely inactive towards emulsified tributyrin, though were able to bind colipase. Conversely, the horse 45 kDa fragment retained the lipase activity but failed to correctly bind colipase. This work definitely proves that catalysis and colipase binding are separate events involving topographically distinct regions of the molecule and focuses attention on the role of the C-terminal domain in colipase binding. PMID- 1631041 TI - Molecular dynamics simulations of the whey protein beta-lactoglobulin. AB - Molecular dynamics simulations have been used to model the motions and conformational behavior of the whey protein bovine beta-lactoglobulin. Simulations were performed for the protein by itself and complexed to a single retinol ligand located in a putative interior binding pocket. In the absence of the retinol ligand, the backbone loops around the opening of this interior pocket shifted inward to partially close off this cavity, similar to the shifts observed in previously reported molecular dynamics simulations of the uncomplexed form of the homologous retinol binding protein. The protein complexed with retinol does not exhibit the same conformational shifts. Conformational changes of this type could serve as a recognition signal allowing in vivo discrimination between the free and retinol complexed forms of the beta-lactoglobulin molecule. The unusual bending of the single alpha-helix observed in the simulations of retinol binding protein were not observed in the present calculations. PMID- 1631042 TI - Application of free energy simulations to the binding of a transition-state analogue inhibitor to HIV protease. AB - Free energy simulations (slow-change method) have been used to estimate quantitatively the ratio of the binding constants of (S) and (R) isomers of a novel HIV protease inhibitor, JG365. As a starting geometry, we used the X-ray crystallographic structure of a complex of HIV protease and JG365 provided by A. Wlodawer. According to our results the (S) configuration, i.e. the form previously identified experimentally, binds considerably more tightly to the protease (delta delta G degrees = 2.9 kcal/mol). When the (S) inhibitor is bound, there is a very strong preference for protonation of the Asp125 (rather than the Asp25) residue of the protease. This study is the first to apply a new method for quantitatively assessing the precision of free energies calculated by the slow change method. PMID- 1631043 TI - The crystal state binding of dithionite to deoxy-hemoglobin. AB - The crystal state binding of sodium dithionite to deoxyhemoglobin is reported. Dithionite has been used extensively to deoxygenate hemoglobin and myoglobin and there has been considerable interest among users of dithionite about its effect on protein structure and binding site(s). We have determined that dithionite binds to deoxygenated hemoglobin crystals at the interface of two molecules in the crystal lattice. Specific residues involved in hydrogen bonds or salt interactions with dithionite include His116 and His117 of the beta 2 subunit and Lys16 of the alpha 1 subunit of the adjacent hemoglobin molecule. No binding was observed at the symmetry related His116 and 117 beta 1 residues. We have shown that dithionite does not affect the native hemoglobin structure or the binding of several allosteric inhibitors to hemoglobin and can be used to mount T state crystals in the air. PMID- 1631044 TI - Pattern-induced multi-sequence alignment (PIMA) algorithm employing secondary structure-dependent gap penalties for use in comparative protein modelling. AB - A multiple sequence alignment algorithm is described that uses a dynamic programming-based pattern construction method to align a set of homologous sequences based on their common pattern of conserved sequence elements. This pattern-induced multi-sequence alignment (PIMA) algorithm can employ secondary structure dependent gap penalties for use in comparative modelling of new sequences when the three-dimensional structure of one or more members of the same family is known. We show that the use of secondary structure information can significantly improve the accuracy of aligning structure boundaries in a set of homologous sequences even when the structure of only one member of the family is known. PMID- 1631045 TI - A variable gap penalty function and feature weights for protein 3-D structure comparisons. AB - We have developed a variable gap penalty function for use in the comparison program COMPARER which aligns protein sequences on the basis of their 3-D structures. For deletions and insertions, components are a function of structural features of individual amino acid residues (e.g. secondary structure and accessibility). We have also obtained relative weights for different features used in the comparison by examining the equivalent residues in weight matrices and in alignments for pairs of 3-D structures where the equivalencies are relatively unambiguous. We have used the new parameters and the variable gap penalty function in COMPARER to align protein structures in the Brookhaven Data Bank. The variable gap penalty function is useful especially in avoiding gaps in secondary structure elements and the new feature weights give improved alignments. The alignments for both azurins and plastocyanins and N- and C terminal lobes for aspartic proteinases are discussed. PMID- 1631046 TI - Homology model of thyroxine binding globulin and elucidation of the thyroid hormone binding site. AB - The tertiary structure of thyroxine binding globulin (TBG) has been modelled on the basis of its close homology to alpha 1-antitrypsin, the archetype of the serine protease inhibitor (serpin) superfamily. Energy minimization was applied to the model to refine the structure further. The putative thyroid hormone binding region suggested in previous labelling studies was found to exist within a beta-barrel structure of complementary dimensions to the thyroid hormones. The model also revealed that the binding cleft provides the hydrophobic environment and specific ionic interaction sites deemed important for thyroid hormone binding. The model is in good agreement with evidence derived from previously reported T3 and T4 binding, stability and isoelectric focussing studies of TBG and TBG variants. Finally, T4 analogue and drug binding studies have enabled us to postulate the orientation and manner of hormone binding to TBG. This may prove to be of assistance in the development of potent and specific, non-thyroidal ligands and also aid in the understanding of physiological thyroid hormone binding interactions. PMID- 1631047 TI - A robust and efficient automated docking algorithm for molecular recognition. AB - A completely automated method is described for determining the most likely mode of binding of two (macro)molecules from the knowledge of their three-dimensional structures alone. The method is based on well-known graph theoretical techniques and has been used successfully to determine and rationalize the binding of a number of known macromolecular complexes. In this article we present results for a special case of the general molecular recognition problem--given the information concerning the particular atoms involved in the binding for one of the molecules, the algorithm can correctly identify the corresponding (contacting) atoms of the other molecule. The approach used can be easily extended to the general molecular recognition problem and requires the extraction of maximal common subgraphs. In these studies the docking of the macromolecules was achieved without the aid of computer graphics or other visual aids. The algorithm has been used to determine the correct mode of binding of a protein antigen to an antibody in approximately 100 min on a DEC micro VAX 3600. PMID- 1631048 TI - Characterization of the interactions of a bifunctional inhibitor with alpha thrombin by molecular modelling and peptide synthesis. AB - A potent thrombin inhibitor, [D-Phe45, Arg47] hirudin 45-65, that contains an active site-directed sequence D-Phe-Pro-Arg-Pro, an exosite specific fragment hirudin 55-65 (H55-65) and a linker portion hirudin 49-54, was designed based on the hirudin sequence [DiMaio et al. (1990) J. Biol. Chem., 265, 21698-21798]. A three-dimensional model of the complex between the B-chain of human thrombin and the inhibitor [D-Phe45, Arg47] hirudin 45-65 was constructed using molecular modelling starting from the X-ray C alpha coordinates of the thrombin-hirudin complex and the NMR-derived structure of the thrombin-bound hirudin 55-65. The contribution of the H49-54 fragment to the thrombin-inhibitor interaction was deduced by examining a series of analogs containing single glycine substitution and analogs with reduced number of residues within the linker. The results were consistent with the molecular modelling observations i.e. the H49-54 fragment serves the role of a spacer in the binding interaction and could be replaced by four glycine residues. The studies on the interaction of the exosite-directed portion of the inhibitor with thrombin using a series of synthetic H55-65 analogs demonstrated that residues AspH55 to ProH60 play a major role in binding to human thrombin where the side chains of PheH56, IleH59 and GluH57 showed critical contributions. Molecular modelling suggested that these side chains may contribute to inter- and intramolecular hydrophobic and electrostatic interactions, respectively. PMID- 1631049 TI - Evidence for a second conserved arginine residue in the integrase family of recombination proteins. AB - This study was designed to search for new regions of similarity in the integrase family of recombination proteins which consists of 28 members found in bacteria and yeast. A computer method based on an information content analysis has been used to align local regions of homology in the set of unaligned protein sequences from this family. Among the aligned regions with high information content were those containing the known conserved histidine, arginine and tyrosine residues. In addition, a new region was identified containing another arginine residue that appears to be conserved in all members of the family. To test further the importance of this newly identified arginine residue, mutants in the Cre protein from phase P1, a member of this integrase family, have been constructed which alter this residue. The mutations which change arginine to lysine and arginine to cysteine depress catalytic activity but not site-specific binding to the lox site. This result is expected for a conserved active site residue. This computer analysis also provides a means for searching for new members of the integrase family. PMID- 1631050 TI - Minimal sequence requirements for ribozyme activity. AB - The hammerhead ribozyme, as engineered by J. Haseloff and W. L. Gerlach [(1988) Nature (London) 334, 585-591], is an RNA molecule containing two regions of conserved nucleotides, a double helix, called helix II, which connects the two conserved regions, and flanking arms of variable sequence, which hybridize the ribozyme to its specific target. Here we show that this ribozyme may be reduced in size and still retain cleavage activity by replacing helix II with just a few nucleotides that cannot form Watson-Crick base pairs between themselves. Furthermore, the nucleotides replacing helix II and the nucleotides in the flanking arms may be substituted with DNA, and this small, DNA-containing ribozyme is fully as active as the original, full-size ribozyme. Cleavage activity of the minimized ribozyme depends on the number and sequence of the few nucleotides that replace helix II; optimal activity, thus far, is achieved by four or five deoxyribopyrimidines. The minimized ribozyme, or "minizyme," is active as a monomer, as shown by its nearly constant activity over a concentration range varying 25,000-fold, by the mobility of the minizyme substrate complex in nondenaturing polyacrylamide gels as compared with other nucleic acid molecules of known size, and by other observations. These minizymes provide an excellent model system for studying the structure and mechanism of catalytic RNA; they might also be useful in a variety of biological applications. PMID- 1631051 TI - In vitro mutagenesis of biologically active transcripts of beet necrotic yellow vein virus RNA 2: evidence that a domain of the 75-kDa readthrough protein is important for efficient virus assembly. AB - RNA 2 of the multipartite genome of beet necrotic yellow vein virus carries the cistron for 21-kDa viral coat protein at its 5' extremity. The amber termination codon of the coat protein cistron undergoes suppression approximately 10% of the time so that translation continues into an adjacent 54-kDa open reading frame, yielding a 75-kDa readthrough protein. The roles of coat protein and the readthrough protein in infection were investigated with biologically active transcripts of RNA 2. Much of the coat protein cistron of the RNA 2 transcript could be deleted without interfering with viral replication and local lesion formation on leaves, although formation of the rod-shaped virions did not occur. Mutants in which the amber coat protein termination codon was replaced with an ochre codon or a tyrosine codon were also viable. The ochre codon was suppressed both in vitro and in planta. The mutant containing the tyrosine substitution produced only the 75-kDa read-through protein and was deficient in viral assembly. Deletions in the 54-kDa readthrough domain were also viable in planta but had different effects on virus assembly. A deletion in the C-terminal portion of the readthrough domain did not interfere with RNA packaging but, unexpectedly, deletions in the N-terminal portion were assembly deficient, although 21-kDa coat protein was produced in planta. Thus, the 75-kDa protein can apparently intervene in virion assembly even though it has not been detected in purified virions. PMID- 1631052 TI - Stable transformation of a mosquito cell line results in extraordinarily high copy numbers of the plasmid. AB - Stable incorporation of high copy numbers (greater than 10,000 per cell) of a plasmid vector containing a gene conferring resistance to the antibiotic hygromycin was achieved in a cell line derived from the Aedes albopictus mosquito. Plasmid sequences were readily observed by ethidium bromide staining of cellular DNA after restriction endonuclease digestion and agarose gel electrophoresis. The plasmid was demonstrated by in situ hybridization to be present in large arrays integrated in metaphase chromosomes and in minute and double-minute replicating elements. In one subclone, approximately 60,000 copies of the plasmid were organized in a large array that resembles a chromosome, morphologically and in the segregation of its chromatids during anaphase. The original as well as modified versions of the plasmid were rescued by transformation of Escherichia coli using total cellular DNA. Southern blot analyses of recovered plasmids indicate the presence of mosquito-derived sequences. PMID- 1631053 TI - Organ injury associated with extrathymic induction of immune tolerance in doubly transgenic mice. AB - The developmental fate of autoreactive T cells encountering extrathymically expressed self-antigen was studied in a doubly transgenic mouse model system where pancreatic acinar cells expressed H-2Ld and T cells expressed an antigen receptor (2C TCR) specific for H-2Ld. Thymocytes bearing 2C TCR differentiated normally. They were positively selected without evidence of intrathymic clonal deletion. Survival of H-2Ld-bearing skin allografts was significantly prolonged in pancreatic H-2Ld singly and doubly transgenic mice, consistent with an in vivo state of T-cell tolerance. The mechanism of tolerance induction was determined and found to have two components. First, up to 80% of peripheral CD8+2C TCR+ T cells were eliminated. Second, those T cells which escaped elimination had a significantly reduced proliferative response to H-2Ld. Thus, autoreactive T cells can be made self-tolerant through interaction with self-antigen located extrathymically. This is accomplished by a reduction in the percentage of autoreactive T cells as well as by a reduction in the functional capacity of residual T cells. Surprisingly, although pancreatic lymphocytic infiltration and organ injury were absent in exocrine tissue of singly transgenic mice, it was present in doubly transgenic mice. This suggests that when the percentage of autoreactive T cells is high, tolerance induction can be associated with an inflammatory infiltrate in extrathymic tissue where self-antigen is presented. PMID- 1631054 TI - A simple explanation of the electrostatics of the B-to-Z transition of DNA. AB - Whereas the phosphates of B-DNA jut out into the solution, those of Z-DNA, being closer to DNA matter, are less subject to electrostatic screening by counterions. We present simple planar models of B- and Z-DNA that reflect these geometric features. The ionic strength dependence of the difference in the Poisson Boltzmann electrostatic free energy of the models agrees with that measured by Pohl [Pohl, F. M. (1983) Cold Spring Harbor Symp. Quant. Biol. 47, 113-118]. This indicates that the electrostatics of the B-to-Z transition are primarily controlled by a qualitative geometrical difference and not by details of the DNA geometry or by complex electrostatic properties of the ionic solution. PMID- 1631055 TI - [Val12] HRAS downregulates GLUT2 in beta cells of transgenic mice without affecting glucose homeostasis. AB - Glucose-induced insulin release from pancreatic beta cells depends on the beta cell metabolism of glucose, which generates intracellular signals for secretion. The beta-cell glucose transporter isotype GLUT2 and the glucose phosphorylating enzyme glucokinase have both been implicated in coupling insulin secretion to extracellular glucose levels. Here we present evidence that a pronounced decrease in beta-cell GLUT2 has no immediate effect on glucose homeostasis. Analysis of transgenic mice overexpressing human [Val12]HRAS oncoprotein under control of the insulin promoter reveals a great reduction in plasma-membrane GLUT2 levels. These mice are nonetheless able to maintain normal fed and fasting plasma glucose and insulin levels for a period of several months. Insulin secretion studied in isolated islets and the perfused pancreas is characterized by a normal incremental response to increasing glucose concentrations. Glucose metabolism, as measured by glucose phosphorylation and oxidation in isolated islets, shows a normal dose dependence on extracellular glucose concentrations. These findings suggest that normal GLUT2 expression in beta cells is not essential for glucose sensing. The transgenic mice provide an experimental system for studying the role of glucose phosphorylation in regulation of insulin release in the absence of GLUT2. PMID- 1631056 TI - High-speed platelet adhesion under conditions of rapid flow. AB - The recognition of exposed collagen by circulating platelets is an initial step in the formation of the hemostatic plug or a thrombus after vascular injury. Theoretical calculations of the speed of platelet function required for effective hemostasis have suggested very short reaction times. However, it is not known how fast platelets can adhere to collagen under arterial flow conditions or which membrane proteins are involved. We have used a continuous-flow, microaffinity column linked to a resistive-particle counter to detect platelet adhesion. Adhesion of human platelets to native type I collagen was extremely rapid, with exponential half-times as short as 240 ms, and was nearly complete by 2 s. This RGD-independent process was not associated with platelet aggregation or secretion. The monoclonal antibody 6F1 directed against the glycoprotein Ia/IIa complex inhibited adhesion, suggesting that this complex plays an important role in the initial phases of platelet-collagen interaction under flow conditions. In addition, divalent cations were required for adhesion, as indicated by inhibition with EDTA in plasma and the dependence on Mg2+ for washed platelets. PMID- 1631057 TI - Evaluation of luteinizing hormone-releasing hormone antagonistic activity in vitro. AB - Antagonistic analogues of luteinizing hormone-releasing hormone (LHRH) belong to a class of compounds that can be utilized for treatment of some hormone-dependent cancers and gynecologic disorders. Recently, we synthesized and tested a large number of LHRH analogues for LHRH antagonistic activity in the dispersed pituitary cell superfusion system. This fast, reliable, and dynamic system made it possible for us not only to evaluate the relative amounts of an analogue required for suppression of the LH-releasing activity of exogenous LHRH but also provided quantitative data on dynamic interactions between the LHRH analogue, LHRH receptors, and LH secretion. Three experimental paradigms were used: (i) LHRH responses after preincubation with the antagonist, (ii) pulsatile, simultaneous infusion of LHRH and the antagonistic analogue, and (iii) effects of the analogues on ongoing, continuous LH secretion induced by prolonged stimulation with LHRH. From the data obtained, we conclude that (i) the suppression of the LHRH-induced LH release was more effective and longer lasting when the cells were preincubated with the antagonistic analogues before the LHRH stimulation than in the case of simultaneous exposure; (ii) not only the potency but also the time of onset and the duration of the LH release-suppressing activity varied according to the different peptides used, resulting in different shapes of response curves; and (iii) from the accurate data obtained in this dynamic system, quantitative parameters of the in vivo interactions between the antagonists and LHRH on the LHRH receptor can be calculated. PMID- 1631058 TI - Regulation of immediate early gene expression and AP-1 binding in the rat nucleus accumbens by chronic cocaine. AB - Chronic treatment of rats with cocaine leads to long-term biochemical changes in the nucleus accumbens (NAc), a brain region implicated in mediating the reinforcing effects of cocaine and other drugs of abuse. Immediate early genes (IEGs) and their protein products appear to play an important role in transducing extracellular stimuli into altered patterns of cellular gene expression and, therefore, into long-term changes in cellular functioning. We therefore examined changes in the mRNA levels for the IEGs c-fos, c-jun, fosB, junB, and zif268 in the NAc of rats treated acutely and chronically with cocaine. A single cocaine injection increased the mRNA levels of all of the IEGs examined. Following chronic cocaine treatment, however, IEG expression had returned to control levels and was not significantly increased following a further acute challenge with cocaine, suggesting desensitization in the ability of cocaine to induce these IEGs. Similarly, levels of Fos-like immunoreactivity, which are increased in the NAc by acute cocaine, were reduced to control levels in chronic cocaine-treated rats. Fos, Jun, and a number of related proteins activate or repress transcription of genes by binding to DNA response elements called AP-1 sites. As would be expected from the RNA data and immunohistochemistry, acute cocaine administration increased AP-1 binding activity in the NAc, an effect that reverted completely to control levels within 8-12 hr. In contrast, AP-1 binding activity in the NAc of animals treated chronically with cocaine remained elevated at acute levels 18 hr after the last chronic injection, a time at which c-fos and c-jun mRNA levels and Fos-like immunoreactivity had returned to control values. An additional acute cocaine challenge did not further increase AP-1 binding. The data suggest that chronic cocaine treatment leads to a persistent increase in AP 1 binding activity, which may be involved in some of the physiological and behavioral aspects of cocaine addiction. PMID- 1631059 TI - Gene expression in cotton (Gossypium hirsutum L.) fiber: cloning of the mRNAs. AB - Cotton, an important natural fiber, is a differentiated epidermal cell. The number of genes that are active in fiber cells is similar to those in leaf, ovule, or root tissues. Through differential screening of a fiber cDNA library, we isolated five cDNA clones that are preferentially expressed in fiber. One of the cDNA clones, pCKE6, corresponded to an abundant mRNA in fiber. Transcripts for E6 were detected throughout the development of the fiber. Immunoprecipitation of in vitro translation products and Western blot analysis of fiber proteins showed two polypeptides in the range of 30-32 kDa as the products of E6 mRNA. Sequence analysis and hybrid-selected RNA translation also suggest that E6 mRNAs encode two polypeptides. Concentrations of E6 mRNA and protein are highest during the late primary cell wall and early secondary cell wall synthesis stages. Sequence comparison of E6 with other known eukaryotic and prokaryotic genes reveals no significant homology (GenBank; December 1991). E6 or a homologous gene(s) is conserved in several members of Malvaceae as well as in one other fiber-producing plant, kapok, but is not found in several other plants examined or in Acetobacter xylinum. A genomic clone corresponding to pCKE6 was isolated, and the promoter element of the E6 gene was shown to direct the expression of a carrot extensin mRNA in a tissue-specific and developmentally regulated fashion in transgenic cotton plants. PMID- 1631060 TI - On the definition of the concepts thinking, consciousness, and conscience. AB - A complex system (CS) is defined as a set of elements, with connections between them, singled out of the environment, capable of getting information from the environment, capable of making decisions (i.e., of choosing between alternatives), and having purposefulness (i.e., an urge towards preferable states or other goals). Thinking is a process that takes place (or which can take place) in some of the CS and consists of (i) receiving information from the environment (and from itself), (ii) memorizing the information, (iii) the subconscious, and (iv) consciousness. Life is a process that takes place in some CS and consists of functions i and ii, as well as (v) reproduction with passing of hereditary information to progeny, and (vi) oriented energy and matter exchange with the environment sufficient for the maintenance of all life processes. Memory is a complex of processes of placing information in memory banks, keeping it there, and producing it according to prescriptions available in the system or to inquiries arising in it. Consciousness is a process of realization by the thinking CS of some set of algorithms consisting of the comparison of its knowledge, intentions, decisions, and actions with reality--i.e., with accumulated and continuously received internal and external information. Conscience is a realization of an algorithm of good and evil pattern recognition. PMID- 1631062 TI - In vivo protein-DNA interactions at hypersensitive site 3 of the human beta globin locus control region. AB - The expression of beta-globin genes in developing erythroid cells is dependent on distant, upstream regulatory sequences, known as the locus control region (LCR), which are marked in chromatin by DNase I hypersensitive sites (HS-1 to HS-4). Linkage of the beta-globin gene complex LCR or fragments surrounding core regions of 200-300 base pairs to the human beta-globin gene permits consistent, high level expression of the transgene in mice. To define the array of nuclear factors interacting with beta-LCR HS-3, we have performed in vivo dimethyl sulfate footprinting of the active HS-3 core in erythroid cells by a modified procedure that permits assessment of protein-DNA contacts at adenine, as well as guanine, residues. In vivo protein occupancy differs considerably from that predicted from previous in vitro binding analyses. In vivo footprinting detects protein binding at four sites recognized by the erythroid transcription factor GATA-1, at two CACC/GT motifs, and at a single AP-1/NF-E2 site. The regulatory elements occupied in vivo in HS-3 appear similar to those described previously in globin gene promoters and 3' enhancers. These findings suggest that the distinctive properties of the HS-3 region may be attributable to the organization of these occupied motifs and the consequent protein interactions, rather than to the binding of unique LCR regulatory factors. PMID- 1631061 TI - Protein interaction cloning in yeast: identification of mammalian proteins that react with the leucine zipper of Jun. AB - To identify proteins that interact with Jun or Fos we have used the protein interaction cloning system developed by S. Fields and O.-K. Song [(1989) Nature (London) 340, 245-246] to clone mammalian cDNAs encoding polypeptides that interact with the dimerization and DNA-binding motif (bZIP; basic domain leucine zipper motif) of Jun. For this purpose, yeast cells lacking GAL4 activity but expressing a GAL4 DNA-binding domain-Jun bZIP fusion protein were transformed with a mouse embryo cDNA plasmid library in which the cDNA was joined to a gene segment encoding the GAL4 transcriptional activation domain. Several transformants exhibiting GAL4 activity were identified and shown to harbor plasmids encoding polypeptides predicted to form coiled-coil structures with Jun and/or Fos. One of these is a bZIP protein of the ATF/CREB protein family- probably the murine homolog of TAXREB67. Two others encode polypeptides with predicted potential to form coiled-coil structures, and seven other isolates encode segments of alpha- or beta-tropomyosin, classical coiled-coil proteins. The tropomyosin polypeptides were found to interact in the yeast assay system with the bZIP region of Jun but not with the bZIP region of Fos. Our results illustrate the range of protein interaction cloning for discovering proteins that bind to a given target polypeptide. PMID- 1631064 TI - Plants transformed with a region of the 201-kilodalton replicase gene from pea early browning virus RNA1 are resistant to virus infection. AB - The 3' proximal portion of the gene encoding the 201-kDa putative replicase protein from the Tobravirus pea early browning virus (PEBV) can potentially be expressed separately as a 54-kDa protein. Nicotiana benthamiana plants transformed with the open reading frame (ORF) encoding the 54-kDa protein, designated 54K ORF, were resistant to infection by purified PEBV at inoculum doses of up to 1 mg/ml, the highest concentration tested. However, resistance was abolished by the introduction into the 54K ORF of mutations that would cause premature termination of translation. This suggests that the resistance mechanism requires the involvement of an intact 54-kDa protein. The 54K ORF-transformed plants were also resistant to infection by broad bean yellow band virus and an uncharacterized isolate of British PEBV (PGRO R) but were not resistant to infection by two other tobraviruses, pepper ringspot virus and the I6 isolate of tobacco rattle virus. Additionally, two variants of PEBV which overcame 54K ORF mediated resistance have been isolated, the analysis of which might provide important information about both the resistance mechanism itself and the process of normal virus replication. PMID- 1631063 TI - Expression of the cholecystokinin gene in pediatric tumors. AB - We have examined a wide range of cultured human tumor cell lines and found that a specific subset of tumors expresses the cholecystokinin (CCK) gene. All neuroepitheliomas (eight) and Ewing sarcoma (eight) cell lines that were tested express CCK RNA. In addition, two of six rhabdomyosarcoma cell lines also express the CCK gene, suggesting that rhabdomyosarcomas are probably heterogenous and that a subset may be similar to Ewing sarcoma and neuroepithelioma. Very few of the positive tumors express completely processed immunoreactive CCK. However, we have used a radioimmunoassay that detects the CCK precursor to demonstrate synthesis of CCK precursor-like peptides by all of the Ewing sarcoma and neuroepithelioma lines that were tested and by the rhabdomyosarcoma cell line that expresses CCK mRNA. These data demonstrate a consistent association of CCK gene expression with a specific group of human neoplasms. The data also add credence to the theory that Ewing sarcoma and neuroepithelioma are derived from the same transformed cell type. Finally, our results suggest that CCK gene expression may serve as a marker to distinguish these tumors, which are considered to be small-round-cell tumors of childhood, from other pediatric tumors. PMID- 1631065 TI - Identification of the major soluble cuticular glycoprotein of lymphatic filarial nematode parasites (gp29) as a secretory homolog of glutathione peroxidase. AB - We have cloned and identified the major cuticular glycoprotein (gp29) of lymphatic filarial nematode parasites as a homolog of the antioxidant enzyme glutathione peroxidase. The derived amino acid sequence predicted a protein of 25.8 kDa, with an amino-terminal hydrophobic signal peptide and two sites for N linked glycosylation, consistent with the documented properties of gp29. Transcription of a full-length cDNA in an SP65 vector and subsequent translation of the RNA in reticulocyte lysates in vitro generated a protein of 27 kDa, which was glycosylated upon the addition of pancreatic microsomal membranes. A postulated role for this secreted enzyme could be inhibition of the oxidative burst of leukocytes and neutralization of secondary products of lipid peroxidation, thus providing one explanation for the resistance of these parasites to immune effector mechanisms and their persistence in the mammalian host. PMID- 1631066 TI - Heterotrimeric G proteins in synaptoneurosome membranes are crosslinked by p phenylenedimaleimide, yielding structures comparable in size to crosslinked tubulin and F-actin. AB - We have treated rat brain synaptoneurosomes with the crosslinking agent N,N'-1,4 phenylenedimaleimide under conditions that cause extensive crosslinking of tubulin, F-actin, and the alpha and beta subunits of three major types of heterotrimeric GTP-binding regulatory proteins (G(o), Gs, Gi) present in brain membranes. The major crosslinked products are coeluted from Bio-Gel sizing columns as very large structures that do not penetrate stacking gels during SDS/PAGE. The alpha subunits but not the beta subunits of Gs, G(o) and Gi also yield crosslinked products of intermediate sizes. None of the products are as small as the heterotrimeric G proteins extracted from brain by cholate or Lubrol. However, the large and intermediate crosslinked structures are strikingly similar to the large, polydisperse structures of the alpha subunits of Gs, Gi, and G(o) extracted from synaptoneurosomes by the detergent octyl glucoside, which have sedimentation properties of multimeric proteins. Several ways in which multimeric forms of G proteins can explain the dynamic and pleiotropic actions of hormones and GTP on signal-transducing systems are discussed. PMID- 1631068 TI - Determinant nucleotides of yeast tRNA(Asp) interact directly with aspartyl-tRNA synthetase. AB - The interaction of wild-type and mutant yeast tRNA(Asp) transcripts with yeast aspartyl-tRNA synthetase (AspRS; EC 6.1.1.12) has been probed by using iodine cleavage of phosphorothioate-substituted transcripts. AspRS protects phosphates in the anticodon (G34, U35), D-stem (U25), and acceptor end (G73) that correspond to determinant nucleotides for aspartylation. This protection, as well as that in anticodon stem (C29, U40, G41) and D-stem (U11 to U13), is consistent with direct interaction of AspRS at these phosphates. Other protection, in the variable loop (G45), D-loop (G18, G19), and T-stem and loop (G53, U54, U55), as well as enhanced reactivity at G37, may result from conformational changes of the transcript upon binding to AspRS. Transcripts mutated at determinant positions showed a loss of phosphate protection in the region of the mutation while maintaining the global protection pattern. The ensemble of results suggests that aspartylation specificity arises from both protein-base and protein-phosphate contacts and that different regions of tRNA(Asp) interact independently with AspRS. A mutant transcript of yeast tRNA(Phe) that contains the set of identity nucleotides for specific aspartylation gave a phosphate protection pattern strikingly similar to that of wild-type tRNA(Asp). This confirms that a small number of nucleotides within a different tRNA sequence context can direct specific interaction with synthetase. PMID- 1631067 TI - Whole genome amplification from a single cell: implications for genetic analysis. AB - We have developed an in vitro method for amplifying a large fraction of the DNA sequences present in a single haploid cell by repeated primer extensions using a mixture of 15-base random oligonucleotides. We studied 12 genetic loci and estimate that the probability of amplifying any sequence in the genome to a minimum of 30 copies is not less than 0.78 (95% confidence). Whole genome amplification beginning with a single cell, or other samples with very small amounts of DNA, has significant implications for multipoint mapping by sperm or oocyte typing and possibly for genetic disease diagnosis, forensics, and the analysis of ancient DNA samples. PMID- 1631069 TI - Functional conversion of the homologous proteins alpha-lactalbumin and lysozyme by exon exchange. AB - Exons of eukaryotic genes that encode proteins frequently appear to encode structural and/or functional protein units [Gilbert, W. (1978) Nature (London) 271, 501; Blake, C.C.F. (1979) Nature (London) 277, 598]. alpha-Lactalbumin and c type lysozyme are functionally quite different but structurally highly homologous proteins. Their gene organizations have been shown to be virtually the same and their exon structures are identical. The exon 2 region of hen lysozyme contains most of the amino acid residues that make up its catalytic cleft. In this study, we engineered a hybrid protein in which the exon 2 region of goat alpha lactalbumin was replaced with that of hen lysozyme. This conferred catalytic activity on the alpha-lactalbumin, which is a nonenzymatic protein in its native structural form. PMID- 1631070 TI - Fumarase C, the stable fumarase of Escherichia coli, is controlled by the soxRS regulon. AB - Fumarase C was strongly induced by paraquat in a parental strain of Escherichia coli but was not induced in a strain lacking the soxRS response. Moreover, a strain that constitutively expresses the soxRS regulon contained more fumarase C than did the parental strain. The Mn-containing superoxide dismutase and glucose 6-phosphate dehydrogenase, members of the soxRS regulon, were similarly induced by paraquat. Mutational defects in glucose-6-phosphate dehydrogenase increased the induction of fumarase C by paraquat. For Mn-containing superoxide dismutase, responsiveness to paraquat was also enhanced in the glucose-6-phosphate dehydrogenase-defective strains. Overproduction of the Mn-containing superoxide dismutase, elicited by isopropyl beta-D-thiogalactoside in a tac-sodA fusion strain, did not diminish induction of fumarase C or of glucose-6-phosphate dehydrogenase by paraquat, and induction of these enzymes was more sensitive to paraquat when the cells were growing on succinate rather than on LB medium. These results indicate that fumarase C is a member of the soxRS regulon and that this regulon does not respond to changes in O2- concentration but perhaps does respond to some consequence of a decrease in the ratio of NADPH to NADP+. PMID- 1631071 TI - Specific binding of the diphtheria tox regulatory element DtxR to the tox operator requires divalent heavy metal ions and a 9-base-pair interrupted palindromic sequence. AB - The structural gene for diphtheria toxin, tox, is carried by a family of closely related corynebacteriophages; however, the regulation of tox expression is controlled by a Corynebacterium diphtheriae-encoded regulatory element, dtxR. The molecular cloning and sequence analysis of dtxR was recently described. Previous studies have suggested that DtxR-mediated regulation of the diphtheria tox operator involves the formation of an iron-repressor complex, which specifically binds to the tox operator. We have expressed and purified DtxR from recombinant Escherichia coli. Immunoblot analysis shows DtxR to be a single M(r) 28,000 protein band in both recombinant E. coli and the C7(-) and C7hm723(-) strains of C. diphtheriae. In addition, we demonstrate that the binding of DtxR to a diphtheria tox promoter/operator probe requires the addition of Mn2+ to the reaction mixture; however, binding may be blocked by addition of the chelator 2,2'-dipyridyl, anti-DtxR antiserum, and excess unlabeled probe to the reaction mixture. Deletion of one of the 9-base-pair inverted repeat sequences from the tox operator results in a loss of DtxR binding. The results presented here demonstrate that regulation of diphtheria toxin expression by DtxR requires direct interaction between this regulatory factor and the tox operator in the presence of a divalent heavy metal ion. PMID- 1631072 TI - Clonal proliferation of murine lymphohemopoietic progenitors in culture. AB - We have used a two-step clonal culture system to unequivocally demonstrate that individual primitive lymphohemopoietic progenitor cells have the capacity for differentiation along either the myeloid or the B-lymphoid lineage. Highly enriched murine marrow cells were plated individually in culture by micromanipulation in the presence of pokeweed mitogen-stimulated spleen cell conditioned medium, erythropoietin, steel factor (SF), and interleukin (IL) 7. Forty-five percent of the single cells formed primary colonies expressing multiple hemopoietic lineages. When aliquots from individual colonies were replated in secondary methyl cellulose culture containing SF and IL-7, 41% of the primary colonies gave rise to lymphocyte colonies. Cells of the lymphocyte colonies were blast-like and B220+, sIg-, Mac-1-, Gr-1-, Ly-1-, L3T4-, Ly-2-, and CD3-. Thirty to 70% of the cells were Thy-1+. mu-chain mRNA was detected in most of the cells by in situ hybridization with an antisense RNA probe. When lymphocyte colonies derived from a single cell were pooled and individually injected into scid mice, donor-type IgM was measurable in the serum of mice and spleens contained donor-type B cells. We then carried out initial screening of growth factors to identify growth factors that might replace pokeweed mitogen stimulated spleen cell conditioned medium in the primary culture. Combinations of two factors that included SF plus IL-6, IL-11, or granulocyte colony-stimulating factor were all effective in the primary culture in the maintenance of the B lymphoid potential. Interestingly, IL-3 could neither replace nor act synergistically with SF to support the lymphoid potential of the primary cultures. Our observations demonstrate that many primitive progenitors previously believed to be myeloid-committed also possess B-lymphoid potential. This culture system should prove valuable for elucidation of the mechanisms regulating early stages of lymphohemopoiesis. PMID- 1631073 TI - Nonconservative recombination in Escherichia coli. AB - Homologous recombination between two duplex DNA molecules might result in two duplex DNA molecules (conservative) or, alternatively, it might result in only one recombinant duplex DNA molecule (nonconservative). Here we present evidence that the mode of homologous recombination is nonconservative in an Escherichia coli strain with an active RecF pathway (a recBC sbcBC mutant). We employed plasmid substrates that enable us to recover both recombination products. These plasmids carry two mutant alleles of neo gene in direct orientation, two drug resistance marker genes, and two compatible replication origins. After their transfer to the cells followed by immediate selection for the recombination to neo+, we could recover only one recombination product. A double-strand break at the region of homology increased this nonconservative recombination. If a nonconservative exchange should leave an end, this end may stimulate another exchange. Such "successive half crossing-over events" can explain several recombination-related phenomena in E. coli, including the origin of plasmid linear multimers and of transcribable, nonreplicated recombination products, and also in yeast and mammalian cells. PMID- 1631074 TI - Two mutations in Marfan syndrome resulting in truncated fibrillin polypeptides. AB - Biochemical and molecular genetic studies have recently suggested that mutations in the gene coding for fibrillin on chromosome 15 result in Marfan syndrome. To our knowledge, only one mutation in the fibrillin gene has been published. Here we report the results of screening 20 unrelated MFS patients for mutations in fibrillin cDNA by the single-strand conformation polymorphism technique. We found two mutations, both of which appear in the heterozygote form and code for a shortened fibrillin polypeptide. The first mutation is a large in-frame deletion of 366 bases of the fibrillin mRNA, shown to result in a truncated but secreted polypeptide found in the fibroblast culture of the patient. The second mutation is a G-to-A transition resulting in the substitution of a stop codon for a tryptophan codon and thus predicting the premature termination of the polypeptide chain. We screened 60 other, unrelated MFS patients for these mutations as well as for the previously reported mutation (arginine-239 to proline) and found none of the three mutations in any of these patients. These data suggest that most MFS families carry their own distinct mutation. PMID- 1631075 TI - Multiple mechanisms mediate glucose repression of the yeast GAL1 gene. AB - Several mechanisms contribute to the glucose repression of the GAL1 gene in Saccharomyces cerevisiae. We show that one mechanism involves the transcriptional down-regulation of the GAL4 gene and a second requires the GAL80 gene. We also examine the contribution of cis-acting negative elements in the GAL1 promoter to glucose repression. In an otherwise wild-type strain disruption of any one of these three mechanisms alleviates repression of GAL1 only 2- to 4-fold. However, in the absence of the other two mechanisms the transcriptional down-regulation of GAL4 is sufficient to repress GAL1 expression 40- to 60-fold and the GAL80 dependent mechanism is sufficient to repress GAL1 expression 20- to 30-fold. These first two mechanisms constitute a functionally redundant system of repression and both must be disrupted in order to abolish glucose repression of GAL1. In contrast, negative elements in the GAL1 promoter are effective in repressing GAL1 expression 2- to 4-fold in glucose medium only when at least one of the other two mechanisms of repression is present. Thus, glucose repression of GAL1 is mediated primarily by the first two mechanisms, whereas the third mechanism supplements repression severalfold. PMID- 1631076 TI - Developmental failure of chimeric embryos expressing high levels of H-2Dd transplantation antigens. AB - The absence of expression of class I products of the major histocompatibility complex at early stages of development is thought to play a key role in maternal tolerance of the fetal allograft. To test this, we developed a strategy that would allow us to describe the consequences of overexpression of the H-2Dd transplantation antigen in the developing embryo. A construct containing the H 2Dd gene under control of the human beta-actin promoter was transfected into pluripotent embryonic stem (ES) cells. Particularly in this case, since overexpression of major histocompatibility complex class I gene products may profoundly affect embryonic development, an important advantage of the ES cell system is the ability to analyze gene expression and study effects on cell growth and differentiation in vitro. ES cells do not constitutively express beta 2 microglobulin. Consistent with this, H-2Dd H chains expressed by ES cell transformants were not associated with beta 2-microglobulin or transported to the cell surface. Significant levels of beta 2-microglobulin and H-2Dd membrane glycoproteins were expressed following differentiation in vitro. H-2Dd transfected ES cells gave rise to a wide range of differentiated cell types, and there was no evidence to suggest that expression of the introduced H-2Dd gene affects the differentiation abilities of ES cells in vitro. When introduced into blastocysts, H-2Dd-transfected ES cells extensively contribute to embryonic and extraembryonic tissues, but this results in the failure of chimeric conceptuses at midgestation. Considering that transgenic chimeras cannot be rescued by transfer into syngeneic foster females, it seems likely that nonimmunological mechanisms are responsible for these prenatal lethalities. PMID- 1631077 TI - Side-chain entropy opposes alpha-helix formation but rationalizes experimentally determined helix-forming propensities. AB - In recent host-guest studies, the helix-forming tendencies of amino acid residues have been quantified by three groups, each obtaining similar results [Padmanabhan, S., Marqusee, S., Ridgeway, T., Laue, T. M. & Baldwin, R. L. (1990) Nature (London) 344, 268-270; O'Neil, K. T. & DeGrado, W. F. (1990) Science 250, 646-651; Lyu, P. C., Liff, M. I., Marky, L. A. & Kallenbach, N. R. (1990) Science 250, 669-673]. Here, we explore the hypothesis that these measured helix-forming propensities are due primarily to conformational restrictions imposed upon residue side chains by the helix itself. This proposition is tested by calculating the extent to which the bulky helix backbone "freezes out" available degrees of freedom in helix side chains. Specifically, for a series of apolar residues, the difference in configurational entropy, delta S, between each side chain in the unfolded state and in the alpha-helical state is obtained from a simple Monte Carlo calculation. These computed entropy differences are then compared with the experimentally determined values. Measured and calculated values are found to be in close agreement for naturally occurring amino acids and in total disagreement for non-natural amino acids. In the calculation, delta S(Ala) = 0. The rank order of entropy loss for the series of natural apolar side chains under consideration is Ala less than Leu less than Trp less than Met less than Phe less than Ile less than Tyr less than Val. Among these, none favor helix formation; Ala is neutral, and all remaining residues are unfavorable to varying degrees. Thus, applied to side chains, the term "helix preference" is a misnomer. While side chain-side chain interactions may modulate stability in some instances, our results indicate that the drive to form helices must originate in the backbone, consistent with Pauling's view of four decades ago [Pauling, L., Corey, R. B. & Branson, H. R. (1951) Proc. Natl. Acad. Sci. USA 37, 205-210]. PMID- 1631078 TI - Characterization of human androgen receptor overexpressed in the baculovirus system. AB - An essential step in the process of understanding the structure and function of the human androgen receptor (hAR) involves the production of large quantities of the hAR. For this purpose, the full-length hAR has been overproduced in insect cells by using a baculovirus genetic expression system. The recombinant hAR is produced in Sf21 insect cells at approximately 7 pmol/mg of protein (1 x 10(6) AR molecules per cell), which is 70-150 times greater than levels detected in androgen target tissues. Androgen can bind to the baculovirus-expressed hAR with high affinity (Kd = 0.46 nM), and the specificity of hormone binding in baculovirus-expressed hAR is essentially identical to that of bona fide hAR. An anti-AR monoclonal antibody can recognize the baculovirus-expressed hAR at approximately 100 kDa upon Western blot analysis. Sucrose gradient analysis shows that baculovirus-expressed hAR complexes sediment at 4 S in a high salt medium and these complexes can interact with anti-AR monoclonal antibody to form complexes that sediment at 8-10 S. Therefore, production of recombinant hAR from the baculovirus expression system will provide an alternative source of biologically active hAR for studies on the molecular mechanisms of androgen action. PMID- 1631079 TI - Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. AB - We report that visual stimulation produces an easily detectable (5-20%) transient increase in the intensity of water proton magnetic resonance signals in human primary visual cortex in gradient echo images at 4-T magnetic-field strength. The observed changes predominantly occur in areas containing gray matter and can be used to produce high-spatial-resolution functional brain maps in humans. Reducing the image-acquisition echo time from 40 msec to 8 msec reduces the amplitude of the fractional signal change, suggesting that it is produced by a change in apparent transverse relaxation time T*2. The amplitude, sign, and echo-time dependence of these intrinsic signal changes are consistent with the idea that neural activation increases regional cerebral blood flow and concomitantly increases venous-blood oxygenation. PMID- 1631080 TI - The cytoplasmic component of the bacterial flagellar motor. AB - We have used electron microscopy to examine freshly isolated Salmonella typhimurium and Escherichia coli basal flagellar fragments, purified without resort to extremes of pH or ionic strength. Such fragments contain the large bell like basal structures visualized recently in freeze-substituted or fixed preparations. We have found mot (non-motile) mutants produced by lesions in fli genes (G, M, N) in which the bell structures do not coisolate with the flagellar basal body. The coisolation of the bell with the flagellar basal body was unaffected in strains lacking the genes for the motility-associated Mot proteins or for the Che family of proteins, which are necessary for chemotaxis. Proper assembly and interaction of the cytoplasmically located bell with the membrane associated flagellar basal structures appears to be necessary for motor function. The FliG, FliM, and FliN proteins are thought to form a structural complex responsible for energization and switching of the flagellar motor. Our findings are consistent with the existence of such a complex and imply that it forms part of the flagellar bell. PMID- 1631081 TI - Estimating substitution rates from molecular data using the coalescent. AB - A coalescent model is used to estimate the rate at which neutral substitutions occur in a DNA sequence, without the necessity for an independent estimate of divergence times. Given a random sample of molecular sequences from a finite population, the distribution of the time to a common ancestor can be obtained from the coalescent model. With this principle, summary statistics are developed that use the distribution of molecular diversity within the sample to estimate the relative magnitude of nucleotide substitution rates. If, in addition, the effective population size is known, absolute substitution rates can also be estimated. These techniques are illustrated by estimating the transition rates that underlie the evolution of the first 360 nucleotides of the mitochondrial control region in an Amerindian tribal population. PMID- 1631082 TI - A promoter element that exerts positive and negative control of the interleukin 2 responsive J-chain gene. AB - In a primary immune response a signal from interleukin 2 (IL-2) induces B lymphocytes to express the gene for the IgM joining component, the J chain. The signaling mechanism was pursued in this study by examining the J-chain gene 5' flanking region for regulatory sequences and interacting nuclear factors. The analyses identified a major control region located between -75 and -45 that encodes two adjacent elements: a T-rich sequence (JA) containing a single positive regulatory motif and an A+G-rich sequence (JB) containing overlapping positive and negative regulatory motifs. Dissection of the two elements indicated that the bifunctional JB sequence is the likely target of the IL-2 signal. The evidence was based on findings that (i) JB activity correlated with J-chain gene transcription--i.e., JB acts as a repressor in J-chain-silent B cells and as an activator in J-chain-expressing cells, and (ii) JB activator function is mediated by a B-cell-specific nuclear protein, NF-JB, that exhibits an IL-2-responsive binding pattern. PMID- 1631083 TI - Identification and molecular characterization of a Salmonella typhimurium gene involved in triggering the internalization of salmonellae into cultured epithelial cells. AB - Penetration of intestinal epithelial cells is an important step in the pathogenesis of Salmonella infections. We have characterized a gene, invE, that is necessary for Salmonella invasion of cultured epithelial cells. The predicted amino acid sequence of InvE showed significant homology to the Yersinia outer membrane protein YopN (LcrE). Strains of Salmonella carrying mutations in invE were unable to penetrate Henle-407 human intestinal cells and Madin-Darby canine kidney cells, although they were fully capable of attaching to the same cells. Unlike wild-type Salmonella typhimurium, invE mutants failed to change the intracellular free calcium levels or the distribution of polymerized actin in cultured epithelial cells; neither did they alter the normal architecture of the microvilli of polarized Madin-Darby canine kidney cells. Wild-type S. typhimurium was able to rescue the invasive phenotype of the invE mutants in simultaneous infections of cultured epithelial cells although it did not rescue the Escherichia coli strain RDEC-1. We hypothesize that invE mutants are deficient in triggering the intracellular events that lead to bacterial internalization. PMID- 1631084 TI - Cloning of a cuticular antigen that contains multiple tandem repeats from the filarial parasite Dirofilaria immitis. AB - An unusual antigen composed of tandemly repeated protein units was cloned from the filarial parasite Dirofilaria immitis. The antigen was initially identified by screening a lambda gt11 cDNA library with serum from dogs immunized with irradiated D. immitis third-stage larvae. DNA sequence analysis of the cDNA clone, Di5, revealed a continuous open reading frame composed of two 399-base pair repeats arranged in tandem. Southern blot analysis of genomic D. immitis DNA showed that the gene coding for Di5 is composed of a tandem array of 25-50 copies of this same 399-base-pair repeat. Antiserum raised against recombinant Di5 protein detected a protein "ladder," from about 14 to greater than 200 kDa with steps approximately 15 kDa apart, on immunoblots of D. immitis extract. Metabolic labeling of adult parasites with [35S]methionine showed that Di5 is synthesized as a large precursor that is subsequently cleaved to produce the ladder-like array. These results suggest that the characteristic ladder is created by proteolytic cleavage of the precursor at the same site in each monomer. The Di5 antigen was localized to the cuticle and hypodermis of adult D. immitis by immunoelectron microscopy. Both male and female parasites were found to release Di5 when cultured in vitro. DNA hybridization analysis demonstrated that Di5 is a member of a gene family present in many filarial parasites that infect both animal and human populations. PMID- 1631085 TI - Binding of the Bacillus subtilis spoIVCA product to the recombination sites of the element interrupting the sigma K-encoding gene. AB - The gene encoding sigma K, a transcription factor controlling mother-cell specific gene expression at a late stage of sporulation, is interrupted by the skin element in Bacillus subtilis. The skin element is excised from the mother cell chromosome by a DNA rearrangement that depends on the spoIVCA gene product. This protein has no other role in sporulation than promoting skin excision and exhibits sequence similarity to a family of bacterial site-specific recombinases. An expression library of B. subtilis DNA in lambda gt11 was screened for the presence of a gene encoding a protein able to bind in vitro to an oligonucleotide matching the inverted repeat sequences present at the ends of the skin element. Several bacteriophages were found to contain the spoIVCA gene. A cell extract containing the SpoIVCA protein protected the inverted repeats and their neighboring sequences from DNase I digestion and methylation. SpoIVCA decreased the electrophoretic mobility of a DNA fragment containing its binding sequence and simultaneously bent the DNA. A single molecule of SpoIVCA bound initially to the repeat sequence followed by binding of a second molecule to create a complex straddling the recombination site. PMID- 1631086 TI - Early persistent activation of sperm K+ channels by the egg peptide speract. AB - Transduction by sperm of the instructive signal provided by the egg peptide speract involves rapid, complex changes in internal ion and cyclic nucleotide content. Here, investigations of hypotonically swollen sperm provide insight into the underlying processes and identify K+ channel activation as an initial ionic event in gamete recognition. A sustained hyperpolarization of swollen sperm is promoted by less than 2.5 pM speract and is followed (with greater than 100 pM speract) by transient repolarization and (with greater than 10 nM speract) by depolarization that is dependent on external Ca2+. Monophasic increases in pHi are produced only by greater than 25 pM speract, indicating that hyperpolarization may not directly promote alkalinization. Increased K(+) selective (K+ greater than Rb+ greater than Cs+ greater than Na+) membrane permeability is found after all speract greater than 2.5 pM, suggesting that hyperpolarization results from persistent activation of K+ channels and that repolarization has a different ionic basis. Supporting this contention, the K+ channel blocker tetraethylammonium (20 mM) inhibits the increased K+ permeability that follows treatment of swollen sperm (and of sperm in seawater) with 2.5 pM speract. Such induced activation of K+ channels is observed in patch-clamped swollen sperm examined in the cell-attached configuration, upon application of 5 50 pM speract to the bath medium. The efficacy of externally applied speract and its potency indicate that activation is indirect and probably involves an as yet unidentified diffusible mediator whose production is promoted by speract at concentrations 0.01-0.001 times those predicted from reported estimates of the Kd for the known speract receptor. PMID- 1631087 TI - Folate receptor allows cells to grow in low concentrations of 5 methyltetrahydrofolate. AB - The folate receptor mediates the uptake of 5-methyltetrahydrofolate in certain cultured cells by a process called potocytosis. When these cells are grown in physiological concentrations of folate, the receptor increases the efficiency of vitamin uptake by 30-fold. We now show that PAM 212 cells, a mouse keratinocyte cell line, are unable to grow in 1 nM 5-methyltetrahydrofolate unless they express a functional folate receptor. These results suggest that under certain conditions, tissue cells in the body may depend on the folate receptor to obtain enough 5-methyltetrahydrofolate for growth. PMID- 1631088 TI - The diabetogenic effects of glucocorticoids are more pronounced in low- than in high-insulin responders. AB - We investigated in six low- and six high-insulin responders (LIR and HIR) the effect of dexamethasone (Dex, 15 mg orally during 48 hr) on oral glucose tolerance (OGTT), glucose turnover under basal conditions and during glucose infusion of 2 mg.kg-1.min-1, and insulin response during hyperglycemic clamp. Dex increased fasting glucose more in LIR (P less than 0.05). During OGTT, Dex caused a more prominent increment in glucose in LIR, whereas the increment in insulin was less in LIR (P less than 0.05). After Dex, in three LIR but in no HIR, a diabetic OGTT was observed. Dex significantly increased basal hepatic glucose production (turnover measured with [6-3H]glucose), hepatic total glucose output (turnover measured with [2-3H]glucose), and glucose cycling (hepatic total glucose output--hepatic glucose production) only in LIR. Dex decreased basal glucose metabolic clearance to the same extent in LIR and HIR. Hyperglycemic clamp revealed that Dex induced a significant increase (P less than 0.05) in insulin response only in HIR. Dex effects on insulin release during hyperglycemic clamp were negatively correlated with the glucose area during Dex OGTT (P less than 0.01). Thus, the double tracer method provided a new insight into the pathogenesis of the steroid effect on carbohydrate tolerance. Dex increased basal glycemia more in LIR because only in LIR was glucose production increased. During OGTT, the LIR who were not able to counteract the effects of Dex by an appropriate enhancement in insulin secretion developed a decreased OGTT. The evaluation of insulin response after Dex may thus allow differentiation of the subset of LIR that run an increased risk of non-insulin-dependent diabetes mellitus. PMID- 1631089 TI - The deep, hot biosphere. AB - There are strong indications that microbial life is widespread at depth in the crust of the Earth, just as such life has been identified in numerous ocean vents. This life is not dependent on solar energy and photosynthesis for its primary energy supply, and it is essentially independent of the surface circumstances. Its energy supply comes from chemical sources, due to fluids that migrate upward from deeper levels in the Earth. In mass and volume it may be comparable with all surface life. Such microbial life may account for the presence of biological molecules in all carbonaceous materials in the outer crust, and the inference that these materials must have derived from biological deposits accumulated at the surface is therefore not necessarily valid. Subsurface life may be widespread among the planetary bodies of our solar system, since many of them have equally suitable conditions below, while having totally inhospitable surfaces. One may even speculate that such life may be widely disseminated in the universe, since planetary type bodies with similar subsurface conditions may be common as solitary objects in space, as well as in other solar type systems. PMID- 1631090 TI - Biosynthesis and endocrine control of the production of the German cockroach sex pheromone 3,11-dimethylnonacosan-2-one. AB - The biosynthesis and endocrine regulation of sex pheromone production in the female German cockroach (Blattella germanica) were determined. Radio-TLC and radio-GLC were used to demonstrate the metabolism of 3,11-dimethylnonacosane, a major cuticular lipid component, to the corresponding alkan-2-ol and methyl ketone. [11,12-3H2]-3,11-Dimethylnonacosan-2-ol was efficiently metabolized to the methyl ketone, and radio-GLC showed that the methyl ketone product from both experiments was coeluted with a methyl ketone standard. A comparison of the metabolism of the labeled dimethylalkane and dimethylalkan-2-ol by age and sex showed that both males and females from day 1 through day 9 after adult emergence readily metabolized the alcohol to the corresponding methyl ketone, whereas only females of 5-9 days postemergence efficiently converted the labeled dimethylalkane to the corresponding methyl ketone. Application of the juvenile hormone analog hydroprene induced significant increases in the conversion of the labeled hydrocarbon to the methyl ketone in starved adult females as well as in females fed a protein-free diet, conditions under which endogenous juvenile hormone biosynthesis is nearly undetectable. These data show that the methyl ketone sex pheromone is formed by the hydroxylation and oxidation of the 3,11 dimethylalkane at the 2 position, show that the age- and sex-specific step in this process is the conversion of 3,11-dimethylnonacosane to 3,11 dimethylnonacosan-2-ol, and provide evidence that juvenile hormone regulates sex pheromone production in the German cockroach. PMID- 1631091 TI - Localized torsional tension in the DNA of human cells. AB - Torsional tension in DNA may be both a prerequisite for the efficient initiation of transcription and a consequence of the transcription process itself with the generation of positive torsional tension in front of the RNA polymerase and negative torsional tension behind it. To examine torsional tension in specific regions of genomic DNA in vivo, we developed an assay using photoactivated psoralen as a probe for unconstrained DNA superhelicity and x-rays as a means to relax DNA. Psoralen intercalates more readily into DNA underwound by negative torsional tension than into relaxed. DNA, and it can form interstrand DNA cross links upon UVA irradiation. By comparing the amount of psoralen-induced DNA cross links in cells irradiated with x-rays either before or after the psoralen treatment, we examined the topological state of the DNA in specific regions of the genome in cultured human 6A3 cells. We found that although no net torsional tension was detected in the bulk of the genome, localized tension was prominent in the DNA of two active genes. Negative torsional tension was found in the 5' end of the amplified dihydrofolate reductase gene and in a region near the 5' end of the 45S rRNA transcription unit, whereas a low level of positive torsional tension was found in a region near the 3' end of the dihydrofolate reductase gene. These results document an intragenomic heterogeneity of DNA torsional tension and lend support to the twin supercoiled domain model for transcription in the genome of intact human cells. PMID- 1631092 TI - Beta 2-microglobulin-, CD8+ T-cell-deficient mice survive inoculation with high doses of vaccinia virus and exhibit altered IgG responses. AB - Transgenic mice lacking an intact beta 2-microglobulin (beta 2m) gene fail to express major histocompatibility complex (MHC) class I proteins on the cell surface and, as a result, are virtually devoid of CD4- CD8+ lymphocytes. These animals provide a unique model system for directly assessing the role of CD8+ lymphocytes in the modulation of viral infection in vivo. beta 2m- CD8- mice and their normal littermates were inoculated at the base of the tail with the WR strain of vaccinia virus and monitored for serum antibody and lesion formation. Both groups developed similar lesions in response to a broad virus dose range, and all animals had completely recovered by day 28 after inoculation. Isotype specific immunoglobulin levels were determined for each animal on day 7 and day 14 after primary inoculation, and again 7 days after a virus challenge. The virus specific IgG1, IgG2a, and IgG2b levels were significantly different in the beta 2m-/- group (20-, 9-, and 30-fold lower, respectively, on day 7 after challenge) compared with the beta 2m+/- group. Virus-specific serum IgM levels for both groups remained similar throughout the experiment. In a separate experiment, beta 2m-/- mice were immunized with a nonviral antigen, 2,4,6-trinitrophenyl conjugated keyhole limpet hemocyanin, and both total and antigen-specific isotype specific immunoglobulin titers were determined. Total IgG1, IgG2a, IgG2b, and IgG3 tended to be lower overall in the beta 2m-/- mice compared with beta 2m+/- littermates. In contrast, total and antigen-specific IgE titers were similar in the two groups. These data indicate that CD8+ lymphocytes are not required to clear high doses of vaccinia virus, and they suggest that beta 2m-/- mice are less efficient at antigen-specific IgG production than their beta 2m+/- littermates. PMID- 1631093 TI - Beta-amyloid precursor protein cleavage by a membrane-bound protease. AB - The principal component of amyloid plaques in Alzheimer disease is beta-amyloid protein, an approximately 4-kDa peptide derived from amyloid precursor proteins. Previous studies have established that amyloid precursor proteins are secreted after proteolytic cleavage within the beta-amyloid peptide. The present investigation documents that, in cultured cells, amyloid precursor protein is cleaved on the plasma membrane by a membrane-bound endoprotease and that the specificity of peptide bond hydrolysis is largely independent of the primary sequence of the precursor. The principal determinants of cleavage appear to be an alpha-helical conformation and the distance (12-13 residues) of the hydrolyzed bond from membrane. PMID- 1631094 TI - Crystal structure of rat liver dihydropteridine reductase. AB - The structure of a binary complex of dihydropteridine reductase [DHPR; NAD(P)H:6,7-dihydropteridine oxidoreductase, EC 1.6.99.7] with its cofactor, NADH, has been solved and refined to a final R factor of 15.4% by using 2.3 A diffraction data. DHPR is an alpha/beta protein with a Rossmann-type dinucleotide fold for NADH binding. Insertion of an extra threonine residue in the human enzyme is associated with severe symptoms of a variant form of phenylketonuria and maps to a tightly linked sequence of secondary-structural elements near the dimer interface. Dimerization is mediated by a four-helix bundle motif (two helices from each protomer) having an unusual right-handed twist. DHPR is structurally and mechanistically distinct from dihydrofolate reductase, appearing to more closely resemble certain nicotinamide dinucleotide-requiring flavin dependent enzymes, such as glutathione reductase. PMID- 1631095 TI - Parametric sequence comparisons. AB - Current algorithms can find optimal alignments of two nucleic acid or protein sequences, often by using dynamic programming. While the choice of algorithm penalty parameters greatly influences the quality of the resulting alignments, this choice has been done in an ad hoc manner. In this work, we present an algorithm to efficiently find the optimal alignments for all choices of the penalty parameters. It is then possible to systematically explore these alignments for those with the most biological or statistical interest. Several examples illustrate the method. PMID- 1631096 TI - Coupling of adenovirus to transferrin-polylysine/DNA complexes greatly enhances receptor-mediated gene delivery and expression of transfected genes. AB - We are developing efficient methods for gene transfer into tissue culture cells. We have previously shown that coupling of a chimeric adenovirus with polylysine allowed the construction of an adenovirus-polylysine-reporter-gene complex that transferred the transporter gene with great efficiency into HeLa cells. We have now explored simpler, biochemical means for coupling adenovirus to DNA/polylysine complexes and show that such complexes yield virtually 100% transfection in tissue culture cell lines. In these methods adenovirus is coupled to polylysine, either enzymatically through the action of transglutaminase or biochemically by biotinylating adenovirus and streptavidinylating the polylysine moiety. Combination complexes containing DNA, adenovirus-polylysine, and transferrin polylysine have the capacity to transfer the reporter gene into adenovirus receptor- and/or transferrin-receptor-rich cells. PMID- 1631097 TI - Cloning of a mu-class glutathione S-transferase gene and identification of the glucocorticoid regulatory domains in its 5' flanking sequence. AB - The expression of a mu-class glutathione S-transferase gene (hGSTYBX) isolated from hamster smooth muscle tumor cells (DDT1 MF-2) is transcriptionally up regulated by glucocorticoids, and this hormonal regulation is dependent upon protein synthesis. To study the mechanism of regulation, we have cloned and sequenced hGSTYBX genomic DNA including its 5' flanking region. The hGSTYBX gene contains nine exons dispersed over a 6.3-kilobase region. When linked to a chloramphenicol acetyltransferase (CAT) reporter gene, the 5' flanking region was able to direct transcription of the reporter gene. With 5' deletion studies, we have localized the major glucocorticoid-inducible regulatory element between nucleotides -353 and -239. Within this region no classic glucocorticoid response element (TGTTCT) was identified, but four potential helix-loop-helix binding domains are embedded in two 16-base-pair repeats. Another glucocorticoid regulatory domain has been localized between nucleotides -239 and -136. Cycloheximide blocks glucocorticoid-induced transcription of both the -353CAT and -239CAT reporter genes (nucleotides -447 to -12 and nucleotides -239 to -12 of hGSTYBX, respectively, ligated to a CAT reporter gene); therefore, our observations support previous results suggesting that hGSTYBX induction by glucocorticoids is a secondary response. PMID- 1631098 TI - Structures of apo and complexed Escherichia coli glycinamide ribonucleotide transformylase. AB - The three-dimensional structure of phosphoribosylglycinamide formyltransferase (10-formyltetrahydrofolate:5'-phosphoribosylglycinamide formyltransferase, EC 2.1.2.2) has been solved both as an apoenzyme at 2.8-A resolution and as a ternary complex with the substrate glycinamide ribonucleotide and a folate inhibitor at 2.5-A resolution. The structure is a modified doubly wound alpha/beta sheet with flexibility in the active site, including a disordered loop in the apo structure, which is ordered in the ternary complex structure. This enzyme is a target for anti-cancer therapy and now for structure-based drug design. PMID- 1631099 TI - Reconstruction of a Streptomyces linear replicon from separately cloned DNA fragments: existence of a cryptic origin of circular replication within the linear plasmid. AB - We report here the reconstruction of a functional linear replicon, the 12 kilobase Streptomyces clavuligerus plasmid pSCL, from separate DNA fragments cloned in Escherichia coli on the pUC19 plasmid. Protein-free DNA molecules containing the full-length pSCL sequence, an internally inserted thiostrepton resistance gene, and adventitious nucleotides external to the pSCL termini were introduced into Streptomyces lividans, where the synthesis and functional attachment of replication proteins occurred and pSCL was established as an extrachromosomal linear replicon. Transformation of S. lividans with uncut supercoilded pUC19/pSCL DNA from E. coli or with a circularized 8-kilobase internal fragment of pSCL yielded circular replicons, indicating the existence of a cryptic origin of circular replication within the linear plasmid. Insertion mutations at sites that prevented the replication of pSCL linear plasmids also interfered with its replication in the circular mode. PMID- 1631100 TI - The endoplasmic reticulum-sarcoplasmic reticulum connection: distribution of endoplasmic reticulum markers in the sarcoplasmic reticulum of skeletal muscle fibers. AB - The skeletal muscle sarcoplasmic reticulum (SR) was investigated for the presence of well-known endoplasmic reticulum (ER) markers: the lumenal protein BiP and a group of membrane proteins recognized by an antibody raised against ER membrane vesicles. Western blots of SR fractions revealed the presence of BiP in fast- and slow-twitch muscles of the rabbit as well as in rat and chicken muscles. Analyses of purified SR subfractions, together with cryosection immunofluorescence and immunogold labeling, revealed BiP evenly distributed within the longitudinal SR and the terminal cisternae. Within the terminal cisternae BiP appeared not to be mixed with calsequestrin but to be distributed around the aggregates of the latter Ca2+ binding protein. Of the various membrane markers only calnexin (91 kDa) was found to be distributed within both SR subfractions, whereas the other markers (apparent molecular masses of 64 kDa and 58 kDa and a doublet around 28 kDa) were concentrated in the terminal cisternae. These results suggest that the SR is a specialized ER subcompartment in which general markers, such as the ones we have investigated, coexist with the major SR proteins specifically responsible for Ca2+ uptake, storage, and release. The differential distribution of the ER markers reveals new aspects of the SR molecular structure that might be of importance for the functioning of the endomembrane system. PMID- 1631101 TI - Cytosolic phospholipase A2 is coupled to hormonally regulated release of arachidonic acid. AB - Cytosolic phospholipase A2 (cPLA2) binds to natural membrane vesicles in a Ca(2+) dependent fashion, resulting in the selective release of arachidonic acid, thus implicating cPLA2 in the hormonally regulated production of eicosanoids. Here we report that the treatment of Chinese hamster ovary (CHO) cells overexpressing cPLA2 with ATP or thrombin resulted in an increased release of arachidonic acid as compared with parental CHO cells, demonstrating the hormonal coupling of cPLA2. In contrast, CHO cells overexpressing a secreted form of mammalian PLA2 (sPLA2-II) failed to show any increased hormonal responsiveness. Interestingly, we have noted that the activation of cPLA2 with a wide variety of agents stimulates the phosphorylation of cPLA2 on serine residues. Pretreatment of cells with staurosporin blocked the ATP-mediated phosphorylation of cPLA2 and strongly inhibited the activation of the enzyme. Increased cPLA2 activity was also observed in lysates prepared from ATP-treated cells and was sensitive to phosphatase treatment. These results suggest that in addition to Ca2+, the phosphorylation of cPLA2 plays an important role in the agonist-induced activation of cPLA2. PMID- 1631102 TI - Enhancer of splitD, a dominant mutation of Drosophila, and its use in the study of functional domains of a helix-loop-helix protein. AB - Helix-loop-helix proteins play important roles in developmental processes, such as myogenesis, neurogenesis, and sex determination. The gene Enhancer of split [E(spl)] of Drosophila, a member of a gene complex that is involved in early neurogenesis, encodes a protein with a basic domain and a helix-loop-helix motif. We took advantage of a dominant mutation of this gene, E(spl)D, to define in vivo structural features of this protein for proper function. The mutation renders the otherwise recessive eye phenotype of spl dominant. By germ-line transformation of different in vitro mutagenized versions of the E(spl) gene, we could demonstrate that the basic domain of this helix-loop-helix protein is functional and necessary for expression of the dominant phenotype. These results are supported by in vitro DNA-binding assays, which showed that the basic domain is in fact necessary for DNA binding, despite the presence of a proline residue. Furthermore, we could show that the dominant enhancement of spl is caused by truncation of the E(SPL)D protein in combination with deletion of a putative regulatory element. PMID- 1631103 TI - Transfer of multiple sclerosis into severe combined immunodeficiency mice by mononuclear cells from cerebrospinal fluid of the patients. AB - To investigate the mode of the pathogenesis of multiple sclerosis (MS), we transferred cerebrospinal fluid (CSF) cells, predominantly mononuclear cells, from MS patients at both exacerbation and remission stages of the disease into severe combined immunodeficiency mice by intracisternal injection. As controls, (i) CSF cells from patients with cervical spondylosis and (ii) peripheral blood mononuclear cells from normal individuals were transferred. Four to 6 weeks after transfer, most mice transferred with CSF cells from MS patients at the exacerbation stage of the disease developed paralysis and ataxia. The histopathological examination on the sacrificed mice revealed multiple scattered, discrete lesions localized in the white matter of the brainstems and spinal cords. These lesions were characterized by various degrees of tissue necrosis, involving inflammatory-cell infiltration. Most infiltrating cells were macrophages, although a smaller number of granulocytes appeared in several foci. Reactive astrocytic gliosis was also seen around the necrotic foci. Furthermore, these lesions exhibited demyelination. These histopathological changes are similar to those seen in MS. In contrast, none of the severe combined immunodeficiency mice transferred with CSF cells from MS patients at the remission stage of the disease, or with CSF cells from the patients with cervical spondylosis, or with peripheral blood mononuclear cells from normal individuals showed any such histopathological changes. These observations provide convincing direct evidence of encephalitogenicity of mononuclear cells in CSF from MS patients at the exacerbation stage of the disease. PMID- 1631104 TI - Changes in intracellular calcium during the development of epithelial polarity and junctions. AB - The "Ca2+ switch" model with cultured Madin-Darby canine kidney (MDCK) cells is useful in studying the biogenesis of epithelial polarity and junction formation and provides insight into early steps in the morphogenesis of polarized epithelial tissues. When extracellular Ca2+ in the medium is changed from less than 5 microM to 1.8 mM, MDCK cells rapidly change from a nonpolarized state exhibiting little cell-cell contact (with the apical membrane and junctional proteins largely within the cell) to a polarized state with well-formed tight junctions and desmosomes. To examine the role of intracellular Ca2+ in the development of polarity and junctions, we made continuous spectrofluorimetric measurements of intracellular Ca2+ during the "switch," using the fluorescent indicator fura-2. Intracellular Ca2+ increased greater than 10-fold during the switch and gave a complex pattern of increase, decrease, and stabilization. In contrast, intracellular pH [monitored with 2',7'-bis(2-carboxyethyl)-5(and 6) carboxyfluorescein (BCECF)] did not change during the period studied. When intracellular Ca2+ curves in several cells were compared, considerable heterogeneity in the rate of increase of intracellular Ca2+ levels and in peak levels was evident, perhaps reflecting the heterogeneity among cells in establishing junctions and polarity. The heterogeneity of the process was confirmed by digital imaging of intracellular Ca2+ and was present even in a "clonal" line of MDCK cells, indicating the heterogeneity was intrinsic to the process and not simply a function of slight genetic variation within the population of MDCK cells. In pairs of cells that had barely established cell-cell contact, often one cell exhibited a much greater increase in intracellular Ca2+ than the other cell in the pair. At the site of cell-cell contact, an apparent localized change (an increase over the basal level) in intracellular Ca2+ was frequently present and occasionally appeared to extend beyond the point of cell cell contact. Since the region of cell-cell contact is also the site where junctions form and where vesicles containing apical membranes fuse during the development of polarity, we postulate a role for global and local changes in intracellular Ca2+ in these events. PMID- 1631105 TI - DHR3: a Drosophila steroid receptor homolog. AB - In Drosophila the steroid hormone ecdysone triggers a genetic regulatory hierarchy in which ecdysone combines with a receptor protein to form a complex that induces the transcription of a small class of "early" genes, which encode transcription factors that regulate other genes. We previously reported that one of the early genes, E75, encodes members of the steroid receptor superfamily. Using an E75 hybridization probe, we have identified two additional Drosophila genes that encode members of this superfamily. One of these is the ecdysone receptor gene, EcR, as previously reported. In this work, we examine the sequence, genomic organization, and developmental expression of the other gene, DHR3, which, like E75, encodes one of a growing number of "orphan" receptors for which ligands have not yet been identified. The structure of the DHR3 protein is strikingly similar to that of the MHR3 protein (e.g., 97% amino acid identity for the DNA binding domains), another orphan receptor encoded by an ecdysone inducible early gene of another insect, Manduca sexta. The temporal developmental profile for DHR3 expression closely parallels that for the ecdysone titer and for the ecdysone-inducible E75 and E74 Drosophila early genes. The structural similarity to a Manduca early gene and the expression similarities to Drosophila early genes suggest that the DHR3 gene may also belong to the early gene class. PMID- 1631106 TI - The complete sequence of Drosophila beta-spectrin reveals supra-motifs comprising eight 106-residue segments. AB - The alpha and beta chains of spectrin are homologous, yet they have acquired different structural features that work in synergy to give the multimer its overall properties. The primary amino acid sequence of each spectrin subunit is dominated by tandemly repeated 106-residue motifs. By comparing the complete Drosophila beta-spectrin sequence with other spectrins we have discovered evidence that a higher-order, 848-amino acid supra-motif is tandemly repeated in both alpha- and beta-spectrin. These data argue that alpha- and beta-spectrin, rather than evolving independently from sequences encoding the ancestral 106 residue motifs, must have arisen after the establishment of a large supra-motif composed of eight of the 106-residue motifs. Our data suggest the segment structure of a progenitor gene that gave rise to both alpha- and beta-spectrin as well as dystrophin. The structural differences that evolved after the split between the alpha- and beta-spectrin genes confer the independent functions that exist in their products today. PMID- 1631107 TI - Rapid decline of chronic myeloid leukemic cells in long-term culture due to a defect at the leukemic stem cell level. AB - In this report we describe a quantitative in vitro assay for the most primitive type of leukemic precursors yet defined in patients with chronic myeloid leukemia (CML). This assay is based on the recently described "long-term culture initiating cell" (LTC-IC) assay for primitive normal human hematopoietic cells. Such cells, when cocultured with competent fibroblast feeder layers, give rise after a minimum of 5 weeks to multiple single and multilineage clonogenic progenitors detectable in secondary semisolid assay cultures. Similar cultures initiated by seeding a highly enriched source of leukemic cells from patients onto normal feeders showed the clonogenic cell output after 5 weeks to be linearly related to the input innoculum over a wide range down to limiting numbers of input cells, thus allowing absolute frequencies of leukemic LTC-ICs to be determined using standard limiting dilution analysis techniques. Leukemic LTC IC concentrations in CML marrow were found to be decreased, on average to less than 10% of the normal LTC-IC concentration in normal marrow, but were greatly increased (up to greater than 10(5) times) in CML blood. Assessment of the number of clonogenic cells produced per leukemic LTC-IC by comparison to normal blood or marrow LTC-IC values showed this function to be unchanged in leukemic LTC-ICs [i.e., 3.1 +/- 0.4 clonogenic cells per CML LTC-IC (mean +/- SEM, n = 6) versus 3.7 +/- 1.2 (n = 3) and 4.3 +/- 0.4 (n = 5), respectively, for normal blood and marrow LTC-ICs]. In contrast, leukemic LTC-IC maintenance in LTC proved to be highly defective by comparison to normal LTC-IC of either blood or marrow origin. Thus, when cells from primary LTC were subcultured into secondary LTC-IC assays, leukemic LTC-IC rapidly declined (greater than 30-fold) within the first 10 days of culture, whereas normal LTC-IC numbers remained unchanged during this period. These findings illustrate how self-maintenance and differentiation events in primitive human hematopoietic cells can be differentially modulated by an oncogenic process and provide a framework for further studies of their manipulation, analysis, and therapeutic exploitation. PMID- 1631108 TI - Selective stimulation of prostatic carcinoma cell proliferation by transferrin. AB - Aggressive prostatic carcinomas most frequently metastasize to the skeletal system. We have previously shown that cultured human prostatic carcinoma cells are highly responsive to growth factors found in human bone marrow. To identify the factor(s) responsible for the increased prostatic carcinoma cell proliferation, we fractionated crude bone marrow preparations by using hydroxylapatite HPLC. The major activity peak contained two high molecular weight bands (M(r) = 80,000 and 69,000) that cross-reacted with antibodies to human transferrin and serum albumin, respectively. Bone marrow transferrin, purified to apparent homogeneity by using DEAE-Affi-Gel Blue chromatography, anti-transferrin affinity chromatography, and hydroxylapatite HPLC, markedly stimulated prostatic carcinoma cell proliferation, whereas human serum albumin showed no significant growth factor activity. Marrow preparations, depleted of transferrin by passage over an anti-transferrin affinity column, lost greater than 90% of their proliferative activity. In contrast to the response observed with the prostatic carcinoma cell lines, a variety of human malignant cell lines, derived from other primary sites and metastatic to sites other than bone marrow, showed a reduced response to purified marrow-derived transferrin. These results suggest that rapid growth of human prostatic carcinoma metastases in spinal bone may result from a combination of conditions that include (i) drainage of prostatic carcinoma cells into the paravertebral circulation, (ii) high concentrations of available transferrin in bone marrow, and (iii) increased sensitivity of prostatic carcinoma cells to the mitogenic activity of transferrin. PMID- 1631109 TI - pH-dependent insertion of proteins into membranes: B-chain mutation of diphtheria toxin that inhibits membrane translocation, Glu-349----Lys. AB - To investigate how diphtheria toxin (DT) undergoes pH-dependent membrane translocation in mammalian cells, we have isolated and characterized mutants of the toxin that are defective in acidic-pH-dependent killing of Escherichia coli. Cloned DT secreted to the periplasm of E. coli kills the bacteria under acidic conditions (near pH 5.0) by inserting into and permeabilizing the inner membrane (a mechanism independent of the toxin's ADP-ribosylation activity). Mutant forms of DT with reduced lethality for E. coli were selected by plating the bacteria under acidic conditions. CRM503, one of the full-length mutants selected by this protocol, also showed diminished cytotoxicity for mammalian cells. We traced the altered cytotoxicity of CRM503 to a Glu-349----Lys mutation (E349K), one of three point mutations, within the B fragment. The E349K mutation alone inhibited cytotoxicity and membrane translocation in mammalian cells and lethality for E. coli but did not affect enzymic activity or receptor binding. The recently determined crystallographic model of DT shows that Glu-349 resides within a short loop connecting two long hydrophobic alpha-helices of the translocation domain. Protonation of Glu-349 and two other nearby acidic residues, Asp-352 and Glu-362, may enable these helices to undergo membrane insertion and the intervening loop to be transferred to the opposite face of the bilayer. The E349K mutation introduces a positive charge at this site, which would be expected to inhibit membrane insertion and the insertion-dependent activities of DT. These results suggest that protonation of Glu-349 and nearby acidic residues may be important in triggering the translocation step of toxin action. PMID- 1631110 TI - Reversion of recombinant toxoids: mutations in diphtheria toxin that partially compensate for active-site deletions. AB - Deleting an important active-site residue of diphtheria toxin, glutamic acid-148, reduces the toxin's ADP-ribosyltransferase activity by a factor of greater than 10(4). We considered using this mutation to construct a recombinant toxoid for expression by live attenuated vaccines and explored second-site mutations that might cause reversion. Activity was partially restored by substituting glutamic acid for valine-147 or by extending the deletion by five residues toward the NH2 terminus, thereby placing glutamic acid-142 immediately adjacent to tyrosine-149. In both mutants the indicated glutamic acid may occupy a spatial locus similar to that of glutamic acid-148 in the unmutated protein. Simply deleting a crucial residue does not, therefore, provide confidence that a second-site mutation could not readily restore activity to a toxoid. PMID- 1631111 TI - Characterization of a periplasmic thiol:disulfide interchange protein required for the functional maturation of secreted virulence factors of Vibrio cholerae. AB - A number of ToxR-regulated genes that encode products required for the biogenesis or function of the toxin-coregulated colonization pilus (TCP) of Vibrio cholerae have been identified previously by TnphoA fusions. In this study we have examined the role of the product of one of these genes, tcpG, to which a fusion results in a piliated cell lacking all of the in vivo and in vitro functions associated with TCP. Our results show that TcpG is not an ancillary pilus adhesin component as suggested by the mutant phenotype but instead is a 24-kDa periplasmic protein that shares active-site homology with several different bacterial thioredoxins and protein disulfide isomerase, as well as overall homology with the disulfide bond-forming DsbA periplasmic oxidoreductase protein of E. coli. Corresponding activity can be demonstrated in vitro for TcpG-enriched fractions from a wild type strain but is absent in a similarly fractionated tcpG-phoA mutant. The phenotype conferred by a tcpG mutation was found to be pleiotropic in nature, also affecting the extracellular secretion of cholera toxin A subunit and a major protease. This suggests a general role for TcpG in allowing a group of virulence associated (and perhaps other) proteins that contain disulfide bonds to assume a secretion or functionally competent state. PMID- 1631112 TI - Fragmentation of proteins in the 13- to 29-kDa mass range observed by 252Cf plasma desorption mass spectrometry. AB - Results are presented on the observation of sequence-specific fragmentation of proteins in the 13- to 29-kDa mass range (ribonuclease A, papain, and proteinase K) by 252Cf-plasma desorption mass spectrometry. For these proteins, extensive N terminal an, cn + 2, and dn fragment ions are observed with mass accuracies approaching 200 ppm for the most prominent fragment ions. The fragmentation pattern of these proteins shows the same fundamental behavior (arginine-directed, charge-remote fragmentation) that is observed in the fragmentation of small peptides, indicating that similar processes are occurring when large proteins and small peptides fragment in plasma desorption mass spectrometry. PMID- 1631113 TI - Interaction between G-protein beta and gamma subunit types is selective. AB - Signal-transducing guanine nucleotide-binding proteins (G proteins) are made up of three subunits, alpha, beta, and gamma. Each of these subunits comprises a family of proteins. The rules for association between members of one family with members of another to form a multimer are not known; it is not clear whether associations are specific or nonspecific. Other than transducin (Gt), the G protein in rod photoreceptors, most purified G proteins contain more than one subtype of beta or gamma subunits. The Gt alpha subunit is associated only with beta 1 and gamma 1. It is not known whether this specificity is due to the differential expression of these subunit types in a cell type or due to intrinsically different affinities between different beta and gamma subunit types. We have used a transfected cell assay system to examine the association of the beta 1, beta 2, and beta 3 proteins with the gamma 1 and gamma 2 proteins. Results show that gamma 1 does not associate with beta 2 and that beta 3 does not associate with gamma 1 or gamma 2. Differences in affinities between types of G protein subunits will impose restrictions on the formation of certain heterotrimers and determine which G protein will be active in a cell. A chimeric molecule of beta 1 and beta 2 was used to broadly map the regions on these subunits that determine specificity of association. PMID- 1631114 TI - Antiproliferative prostaglandins activate heat shock transcription factor. AB - Treatment of human K562 erythroleukemia cells with the antiproliferative prostaglandin A1 results in the elevated transcription of two heat shock genes, HSP70 and HSP90. Parallel with increased heat shock gene transcription is the activation of heat shock transcription factor. Heat shock transcription factor levels are induced within 60 min after prostaglandin A1 addition to levels similar to that achieved during heat shock. The requirement for protein synthesis for prostaglandin A1 activation of heat shock transcription factor suggests that effects on nascent protein synthesis may be involved in the signaling mechanism. Although it is unclear whether the activation of a heat shock response by prostaglandins is relevant to the biochemical properties of these natural substances, cells pretreated with prostaglandin A1 are protected against a subsequent heat shock, indicative of a thermotolerant state. PMID- 1631115 TI - Targeted oncogene activation by site-specific recombination in transgenic mice. AB - An efficient and accurate method for controlled in vivo transgene modulation by site-directed recombination is described. Seven transgenic mouse founder lines were produced carrying the murine lens-specific alpha A-crystallin promoter and the simian virus 40 large tumor-antigen gene sequence, separated by a 1.3 kilobase-pair Stop sequence that contains elements preventing expression of the large tumor-antigen gene and Cre recombinase recognition sites. Progeny from two of these lines were mated with transgenic mice expressing the Cre recombinase under control of either the murine alpha A-crystallin promoter or the human cytomegalovirus promoter. All double-transgenic offspring developed lens tumors. Subsequent analysis confirmed that tumor formation resulted from large tumor antigen activation via site-specific, Cre-mediated deletion of Stop sequences. PMID- 1631116 TI - Purification and identification of bovine liver gamma-carboxylase. AB - The microsomal gamma-carboxylase catalyzes modification of a limited set of glutamyl residues to gamma-carboxyglutamyl residues in a vitamin K-dependent reaction that also utilizes O2 and CO2. We report the purification to apparent homogeneity of the bovine liver microsomal carboxylase. Affinity chromatography exploiting the association of the carboxylase with prothrombin precursor and carboxylase binding to the propeptide sequence were combined with ion-exchange chromatography and fractionation using immobilized lectins. A 3.5 x 10(5)-fold purification was obtained, which is the highest purification, by a factor of 35, yet reported for this enzyme. A single 98-kDa protein is obtained from this isolation. Carboxylase activity is associated with this protein by two different criteria. Antibodies prepared against the carboxylase detected the 98-kDa protein when used in Western analysis. In addition, the single 98-kDa protein was shown to comigrate with activity when electrophoresed in a nondenaturing gel system. The availability of purified preparations of carboxylase will facilitate an increased understanding of the complex biochemical reaction carried out by this protein. PMID- 1631117 TI - Complexity of sea urchin embryo nuclear proteins that contain basic domains. AB - We describe a quantitative two-dimensional gel electrophoretic analysis of nuclear extract from 24-hr sea urchin embryos. The extract was fractionated by using a weak cation-exchange resin, and eight known DNA-binding proteins were shown to be entirely included in a salt eluate that releases proteins containing basic domains. This fraction and a lower-salt fraction containing the majority of the protein species were mapped two-dimensionally by using new algorithms that permit reproducible spot identification, storage of intensity and map-position data, and subtractive comparison of one pattern with respect to another. By reference to a previously characterized DNA-binding factor, spot intensity could be interpreted in terms of the number of molecules per embryo nucleus. A map was constructed displaying all nuclear proteins containing basic domains that are present within the concentration range per nucleus of a set of known DNA-binding factors of the sea urchin embryo. The map includes 265 spots that fulfill both of these criteria, probably representing about 100 different protein species. PMID- 1631118 TI - An immunophilin that binds M(r) 90,000 heat shock protein: main structural features of a mammalian p59 protein. AB - In the rabbit, a p59 protein included in the untransformed, non-DNA binding, "8 9S," steroid receptor complexes binds heat shock protein M(r) approximately 90,000 (hsp90). Sequence data [Lebeau, M. C., Massol, N., Herrick, J., Faber, L. E., Renoir, J. M., Radanyi, C. & Baulieu, E. E. (1992) J. Biol. Chem. 267, 4281 4284] and hydrophobic cluster analysis delineate, from the N terminus, two successive domains closely related to the immunosuppressant FK506 binding immunophilin FKBP (FK506 binding protein), consistent with recent purification of the human p56 immunophilin cognate protein by FK506 affinity chromatography [Yem, A. W., Tomasselli, A. G., Heinrikson, R. L., Zurcher-Neely, H., Ruff, V. A., Johnson, R. A. & Deibel, M. R., Jr. (1992) J. Biol. Chem. 267, 2868-2871]. The first FKBP-like domain demonstrates all structural characteristics known to be necessary for immunosuppressant binding and for peptidylprolyl cis-trans isomerase (rotamase) activity. Hence, p59 is a "hsp binding immunophilin" (HBI). It is thus speculated that hsp binding immunophilin may help the assembly/disassembly mechanisms involved in steroid receptor trafficking and activity and participate in the poorly understood hsp90 function. ATP/GTP binding likely occurs within the second FKBP-like domain, near the FK506 binding site on the FKBP template. A third domain detected by the hydrophobic cluster analysis method is distantly structurally related to the two first FKBP-like domains and is followed by the C-terminal part of the protein, which contains a calmodulin binding consensus sequence. Hsp binding immunophilin may be involved in a number of immunological, endocrinological, and chaperone-mediated pathways. PMID- 1631119 TI - A microsomal endoprotease that specifically cleaves isoprenylated peptides. AB - A microsomal enzymatic activity is described that can specifically cleave the tetrapeptide N-acetyl-S-farnesyl-L-Cys-L-Val-L-Ile-L-Ser between the isoprenylated cysteine residue and the valine residue. Km and Vmax values are measured as 5.8 microM and 251 pmol/min per mg of protein, respectively. Proteolytic cleavage of the substrate is stereospecific because the substitution of a farnesylated D-cysteine residue for the L-amino acid leads to the abolition of substrate activity. A free carboxyl-terminal group is also required for substrate activity because methyl esterification renders the substrate inert. The tripeptide N-acetyl-S-farnesyl-L-Cys-L-Val-L-Ile and the dipeptide N-acetyl-S farnesyl-L-Cys-L-Val are also hydrolyzed by the protease. Again, stereospecificity is observed at the isoprenylated residue. Hydrolysis of the farnesylated tetrapeptide is not inhibited by a 5-fold excess of the nonfarnesylated tetrapeptide, suggesting that isoprenylation is important for substrate activity. This activity is probably the same as the proteolytic activity proposed to cleave isoprenylated proteins terminating in a Cys-Ali-Ali Xaa motif, where Ali refers to aliphatic amino acid. These proteins include the ras family of G proteins and the heterotrimeric G proteins. Proteolytic maturation of these essential isoprenylated signal-transducing elements is a key step in their activation. PMID- 1631120 TI - Identification of a structural domain that distinguishes the actions of the type 1 and 2 isoforms of transforming growth factor beta on endothelial cells. AB - A chimeric transforming growth factor beta (TGF-beta) molecule has been synthesized to map the amino acids responsible for the substantially greater activity of TGF-beta 1 than TGF-beta 2 on growth and migration of endothelial cells. This chimera consists of a dimer of a monomeric unit composed of amino acids 1-39 of TGF-beta 2, 40-82 of TGF-beta 1, and 83-112 of TGF-beta 2. Structural identity of the purified recombinant protein has been confirmed by immunoblotting and NH2-terminal sequencing. The biological potency of the TGF beta 2-1-2 chimera was equal to that of TGF-beta 1 in inhibition of growth of both fetal bovine heart endothelial cells and rat epididymal fat pad microvascular endothelial cells. Similarly, the TGF-beta 2-1-2 chimera was nearly equivalent to TGF-beta 1 and at least 10-fold more active than TGF-beta 2 in inhibiting migration of bovine aortic endothelial cells. These results identify the sequence between amino acids 40-82 as an important region within TGF-beta that functions to specify a TGF-beta 1- or TGF-beta 2-like activity. PMID- 1631121 TI - Disruption of a binding site for hepatocyte nuclear factor 4 results in hemophilia B Leyden. AB - Hemophilia B Leyden is an X chromosome-linked bleeding disorder characterized by very low plasma levels of blood coagulation factor IX (fIX) during childhood. After puberty, plasma fIX levels gradually rise to a maximum of 60% of normal, probably under the influence of testosterone. Single point mutations in the fIX promoter region of hemophilia B Leyden patients have been reported at -20, -6, 5, +8 and +13. In addition, one promoter mutation (G----C at -26) has been detected that abolishes fIX expression throughout life (M. Ludwig, personal communication). We examined how one of the hemophilia B Leyden mutations (T----A at -20) and the G----C mutation at -26 interfere with fIX gene transcription. We report that the wild-type promoter of the human fIX gene contains a binding site (at nucleotides -34 to -10) for hepatocyte nuclear factor 4 (HNF-4), a member of the steroid hormone receptor superfamily of transcription factors. The binding of HNF-4 is disrupted by both the T----A mutation at -20 and the G----C mutation at 26. Whereas HNF-4 transactivates the wild-type promoter sequence in liver (HepG2) and non-liver (HeLa) cell types quite well, it transactivates the -20 mutated promoter to only a limited extent and the -26 mutated promoter not at all. These data suggest that HNF-4 is a major factor controlling fIX expression in the normal individual and that its inability to bind efficiently to the -20 T----A and the -26 G----C mutated promoter sequence results in hemophilia. Further, the severity of the hemophilia phenotype appears to be directly related to the degree of disruption of HNF-4 binding and transactivation. PMID- 1631122 TI - Localization of the Salmonella typhimurium flagellar switch protein FliG to the cytoplasmic M-ring face of the basal body. AB - The direction of rotation of the bacterial flagellum is determined by the flagellar switch. We have localized FliG, one of the switch proteins of Salmonella typhimurium, to the cytoplasmic face of the M ring of the flagellar basal body. This localization was made possible by the discovery of two spontaneous mutants in which the fliF (M ring) and fliG (switch) genes were fused in-frame. In the first mutant, a deletion of 7 base pairs at the 3' end of fliF resulted in an essentially full-length fusion protein. In the second mutant, a larger deletion resulted in a fusion in which 56 amino acids from the carboxyl terminus of FliF and 94 amino acids from the amino terminus of FliG were lost. Both strains were motile and underwent switching; the first strain had a clockwise bias, and the second strain had a counterclockwise bias. Gel electrophoresis and immunoblotting of isolated hook-basal-body complexes verified that they contained the fusion proteins. Electron microscopy revealed additional mass at the cytoplasmic face of the M ring, which could be decorated with anti FliG antibody. We conclude that the natural location for FliG is at the cytoplasmic face of the M ring and that the stoichiometric ratio between FliF and FliG in wild-type cells is probably 1:1. PMID- 1631123 TI - Selective decreased de novo synthesis of glomerular proteoglycans under the influence of reactive oxygen species. AB - The effect of reactive oxygen species on de novo synthesis of heparan sulfate proteoglycans (HSPGs) of the renal glomerulus was investigated in an organ perfusion system. Isolated kidneys were perfused for 7 hr with a medium containing [35S]sulfate to label sulfated proteoglycans or [35S]methionine to label total glomerular glycoproteins. For the generation of reactive oxygen species, xanthine and xanthine oxidase were included in the perfusion medium, and catalase and superoxide dismutase were used as scavenging agents. Proteoglycans were characterized by Sepharose CL-6B and DEAE-Sephacel chromatographies and SDS/PAGE analysis. The labeled glycoproteins were immunoprecipitated with anti HSPG, anti-type IV collagen, and anti-laminin, and their specific radioactivities were determined. With exposure to reactive oxygen species, a drastic dose dependent decrease in de novo synthesis of proteoglycans was seen, and that effect was reversible by catalase treatment. No alterations in the biochemical characteristics of proteoglycans were noted. Immunoprecipitation studies revealed a 16-fold decrease in the synthesis of nascent core peptide of HSPGs, while at comparable concentrations of xanthine and xanthine oxidase, synthesis of type IV collagen and laminin slightly decreased (approximately 15%). Morphologic studies revealed a 14-fold decrease in [35S]sulfate-associated autoradiographic grains overlying the glomerular basement membrane, a critical component of the ultrafiltration apparatus. Relevance of the selective decreased de novo synthesis of HSPGs of the glomerular basement membrane is discussed in terms of increased glomerular permeability to plasma proteins. PMID- 1631124 TI - Ecdysteroid-dependent regulation of genes in mammalian cells by a Drosophila ecdysone receptor and chimeric transactivators. AB - Steroid receptors are members of a large family of transcription factors whose activity is tightly regulated by the binding of their cognate steroid ligand. Mammalian steroid hormone receptors have been exploited to obtain the regulated expression of heterologous genes in mammalian cells. However, the utility of these systems in cultured cells and transgenic animals is limited by the presence of endogenous steroids and their receptors. We show that a Drosophila ecdysone receptor can function in cultured mammalian cells as an ecdysteroid-dependent transcription factor. The activity of the ecdysone receptor was not induced by any of the mammalian steroid hormones tested. The DNA-binding and transactivation activities of viral, mammalian, or bacterial proteins were rendered ecdysteroid dependent when fused to the ligand-binding domain of the ecdysone receptor. The ecdysone receptor may prove useful in selectively regulating the expression of endogenous or heterologous genes in mammalian cells. PMID- 1631125 TI - Androgen receptor gene mutations in human prostate cancer. AB - We screened human prostate cancer tissues for the presence of somatic mutations in the hormone binding domain of the androgen receptor (AR) gene. Exons E-H were amplified from genomic DNA using the polymerase chain reaction and analyzed by denaturing gradient gel electrophoresis (DGGE), which separates DNA fragments that differ by only a single base. We detected a mutation in exon E of the hormone binding domain in 1 of 26 specimens of untreated organ-confined stage B prostate cancer. The mutation was not detectable in peripheral blood lymphocyte DNA. Lymphocyte DNA (wild-type AR) migrated in DGGE as a single band. The tumor DNA migrated in DGGE as four bands, consistent with the presence of cells with mutant AR plus cells with wild-type AR and indicating that the tumor contained a somatic mutation. To our knowledge, a somatic AR gene mutation has not been reported previously. Sequencing revealed a G----A substitution in codon 730, changing valine to methionine. Codon 730 is in a region highly conserved among all steroid receptors. The abundance of the mutated fragment (about 50% of the DNA in the specimen) indicates its presence in cells with a growth advantage. A somatic mutation could be detected by DGGE if it represented at least 10% of the sample. Failure to detect mutations in other specimens analyzed may be due to this limit of sensitivity, the presence of mutations in other parts of the AR, or a low frequency of mutations in early stage disease. PMID- 1631126 TI - Developmental segregation in the afferent projections to mammalian auditory hair cells. AB - The mammalian ear contains two types of auditory receptors, inner and outer hair cells, that lie in close proximity to each other within the sensory epithelium of the cochlea. In adult mammals, these two classes of auditory hair cells are innervated by separate populations of afferent neurons that differ strikingly in their cellular morphology and their pattern of arborization within the cochlea. At present, it is unclear when or how these distinctive patterns of cochlear innervation emerge and become segregated during development. In the present study, an in vitro horseradish peroxidase labeling method was used to examine the formation of individual auditory neuron arbors at the same location within the apex of the developing gerbil cochlea. At birth, most cochlear neurons displayed peripheral arbors that embraced both inner and outer hair cell receptors. During the next 6 days, however, the arbors of individual cochlear afferents become confined to either the inner or outer hair cell zone, and thus there is a complete segregation of afferent innervation. This neural segregation occurs principally through the withdrawal of inappropriate connections to the outer hair cell system and is completed well before hearing commences. PMID- 1631127 TI - Mutational and nucleotide sequence analysis of S-adenosyl-L-homocysteine hydrolase from Rhodobacter capsulatus. AB - The genetic locus ahcY, encoding the enzyme S-adenosyl-L-homocysteine hydrolase (EC 3.3.1.1) from the bacterium Rhodobacter capsulatus, has been mapped by mutational analysis to within a cluster of genes involved in regulating the induction and maintenance of the bacterial photosynthetic apparatus. Sequence analysis demonstrates that ahcY encodes a 51-kDa polypeptide that displays 64% sequence identity to its human homolog. Insertion mutants in ahcY lack detectable S-adenosyl-L-homocysteine hydrolase activity and, as a consequence, S-adenosyl-L homocysteine accumulates in the cells, resulting in a 16-fold decrease in the intracellular ratio of S-adenosyl-L-methionine to S-adenosyl-L-homocysteine as compared to wild-type cells. The ahcY disrupted strain fails to grow in minimal medium; however, growth is restored in minimal medium supplemented with methionine or homocysteine or in a complex medium, thereby indicating that the hydrolysis of S-adenosyl-L-homocysteine plays a key role in the metabolism of sulfur-containing amino acids. The ahcY mutant, when grown in supplemented medium, synthesizes significantly reduced levels of bacteriochlorophyll, indicating that modulation of the intracellular ratio of S-adenosyl-L-methionine to S-adenosyl-L-homocysteine may be an important factor in regulating bacteriochlorophyll biosynthesis. PMID- 1631128 TI - MT-III, a brain-specific member of the metallothionein gene family. AB - A third member of the metallothionein (MT) gene family, designated MT-III, was cloned by virtue of its homology to a human protein that was shown previously to inhibit neuronal survival in culture and to be deficient in the brains of people with Alzheimer disease. Human and mouse MT-IIIs have two insertions relative to all other known mammalian MTs: a threonine after the fourth amino acid and a block of six amino acids near the carboxyl terminus. The genes encoding MT-III resemble all other mammalian MT genes in their small size and exon/intron organization. The MT-III genes are closely linked to the other functional MT genes on human chromosome 16 and mouse chromosome 8. Mouse MT-III gene expression appears to be restricted to brain; in addition, it fails to respond to zinc, cadmium, dexamethasone, or bacterial endotoxin in vivo, thereby distinguishing MT III from other known MTs. PMID- 1631129 TI - Fast sequencing of oligosaccharides: the reagent-array analysis method. AB - A method of oligosaccharide analysis involving controlled fragmentation resulting from enzymatic digestion is presented. The principle involves generating a set of fragments from the original oligosaccharides, characterizing them in terms of their hydrodynamic volumes, determining their molar proportions, and identifying the oligosaccharides by comparison with a computer-generated data base. Experimentally, this technique involves incubation of aliquots of a sample with a set of defined mixtures of exoglycosidases followed by pooling of the products and a single analysis on the product pool. This method has several practical advantages over current techniques, including speed and the ability to use smaller amounts of starting material. The detection of the intensity-versus hydrodynamic volume profile is limited only by the specific activity of the labeling method. The ability to perform the enzyme digestions is limited by the individual Km values of the enzymes. PMID- 1631131 TI - Conservation of the organization of five tightly clustered genes over 600 million years of divergent evolution. AB - The organization of the mouse surfeit locus is unusual in that it contains six housekeeping genes (Surf-1-Surf-6), which are unrelated by sequence homology, in the tightest mammalian gene cluster thus far described. A maximum of only 73 base pairs separates any two of the four well-characterized genes, and two of the genes overlap at their 3' ends. The direction of transcription of each of the five surfeit genes, Surf-1-Surf-5, alternates with respect to that of its neighbor, suggesting cis-interaction or coregulation between the genes by mechanisms such as the sharing of regulatory elements and/or antisense regulation. The Surf-3 gene has been identified as encoding the ribosomal protein L7a (Rpl7a). We have used the high conservation of the Rpl7a gene to clone the chicken gene and surrounding genomic DNA. The tight clustering and juxtaposition of at least five of the surfeit genes (Surf-1-Surf-5) and their associated CpG rich islands have been found to be conserved over the 600 million years of divergent evolution that separates birds and mammals. This strongly suggests that the surfeit locus represents a different form of gene cluster in which gene organization may play both a positive and negative regulatory role in gene expression possibly via cis-interactions between the closely spaced genes. PMID- 1631130 TI - Cell cycle-dependent initiation and lineage-dependent abrogation of GATA-1 expression in pure differentiating hematopoietic progenitors. AB - The programmed activation/repression of transcription factors in early hematopoietic differentiation has not yet been explored. The DNA-binding protein GATA-1 is required for normal erythroid development and regulates erythroid expressed genes in maturing erythroblasts. We analyzed GATA-1 expression in early human adult hematopoiesis by using an in vitro system in which "pure" early hematopoietic progenitors are induced to gradual and synchronized differentiation selectively along the erythroid or granulocyte-macrophage pathway by differential treatment with hematopoietic growth factors. The GATA-1 gene, though virtually silent in quiescent progenitors, is activated after entrance into the cell cycle upon stimulation with hematopoietic growth factors. Subsequently, increasing expression along the erythroid pathway contrasts with an abrupt downregulation in the granulocyte-macrophage lineage. These results suggest a microenvironment directed, two-step model for GATA-1 expression in differentiating hematopoietic progenitors that involves (i) cycle-dependent initiation and (ii) lineage dependent maintenance or suppression. Hypothetically, on/off switches of lineage restricted transactivators may underlie the binary fate decisions of hematopoietic progenitors. PMID- 1631132 TI - Developmental expression of surface antigen genes in the parasitic ciliate Ichthyophthirius multifiliis. AB - A 1.2-kilobase (kb) cDNA encoding a major surface antigen of the holotrich ciliate Ichthyophthirius multifiliis (an obligate parasite of fish) has been isolated and used as a probe to examine the expression of immobilization antigen (i-antigen) genes in this system. The cDNA encodes a predicted protein of 394 amino acids with a tandemly repeated structure characteristic of the i-antigens of the related free-living ciliates Paramecium and Tetrahymena. As shown by Northern hybridization analysis with both total and poly(A)+ RNAs, the 1.2-kb cDNA recognizes distinct transcripts of 1.6 and 1.9 kb which are differentially expressed through the parasite life cycle. During the transition from the host associated trophozoite stage to the infective tomite stage, steady-state levels of the 1.9-kb RNA undergo a marked increase of greater than or equal to 50-fold, while the 1.6-kb transcript increases only slightly. The absolute amounts of RNA encoding the i-antigen have been quantitated and were found to reach extremely high levels equivalent to approximately 6% of the poly(A)+ RNA of I. multifiliis tomites. Southern hybridization analysis with I. multifiliis genomic DNA suggests that at least two genes encode the i-antigen transcripts. In experiments to examine the effects of temperature on the expression of I. multifiliis i-antigen genes, levels of the 1.6- and 1.9-kb transcripts were found to remain relatively constant in cells maintained at different temperature extremes. These studies indicate that genes encoding i-antigens of I. multifiliis are developmentally regulated, and they suggest the existence of alternative mechanisms for the control of surface antigen expression in ciliates. PMID- 1631133 TI - Distinct sequence of gonadotropin-releasing hormone (GnRH) in dogfish brain provides insight into GnRH evolution. AB - In vertebrates, gonadotropin-releasing hormone (GnRH) belongs to a family of decapeptides characterized by the conservation of residues 1, 2, 4, 9, and 10. In the jawed vertebrates only positions 5, 7, and 8 in the GnRH molecules vary. We have now purified two forms of GnRH from the brains of spiny dogfish (Squalus acanthias) by using reverse-phase high-performance liquid chromatography. The primary structures were established by automated Edman degradation and mass spectral analysis. The distinct structure of the first form (dogfish GnRH) is pGlu-His-Trp-Ser-His-Gly-Trp-Leu-Pro-Gly-NH2 (pGlu represents pyroglutamyl). The second peptide is identical to a form of GnRH originally isolated from chicken brains (chicken GnRH-II; pGlu-His-Trp-Ser-His-Gly-Trp-Tyr- Pro-Gly-NH2) and is widespread throughout the vertebrates. We are aware of no other species of cartilaginous fish in which the primary structures of two forms of GnRH have been determined. The presence of chicken GnRH-II in dogfish supports the idea that chicken GnRH-II is the oldest GnRH to evolve in jawed vertebrates. With the addition of the dogfish GnRH structure to the family, two main structural branches of GnRH can be delineated. The physiological effects of dogfish GnRH included the release of not only gonadotropin but also growth hormone from goldfish pituitary fragments. PMID- 1631134 TI - Conformation-dependent cleavage of staphylococcal nuclease with a disulfide linked iron chelate. AB - We report the synthesis and evaluation of (EDTA-2-aminoethyl) 2-pyridyl disulfide. By using this easily prepared cysteine-specific hydrophilic reagent, an ethylenediaminetriacetic acid-Fe3+ complex (EDTA-Fe) was covalently attached to a single genetically engineered cysteine residue in staphylococcal nuclease. Upon addition of the iron reductant ascorbate, the nuclease-EDTA-Fe conjugate underwent a protein self-cleavage reaction mediated by reactive oxygen species. Sequence analysis of the products indicated that cleavage occurs close in tertiary structure to the EDTA-Fe attachment site. In the presence of denaturants, the cleavage pattern changes and the reaction is limited to residues proximal in sequence to the cysteine attachment site. These results indicate that intramolecular protein cleavage reactions mediated by EDTA-Fe can be used to evaluate changes in protein conformation. The reagent described should be a useful tool in the structural mapping of nonnative protein states populated at equilibrium, such as the molten globule, that are frequently refractory to conventional structure analysis. PMID- 1631135 TI - Isoprenoid addition to Ras protein is the critical modification for its membrane association and transforming activity. AB - We have introduced a variety of amino acid substitutions into carboxyl-terminal CA1A2X sequence (C = cysteine; A = aliphatic; X = any amino acid) of the oncogenic [Val12]Ki-Ras4B protein to identify the amino acids that permit Ras processing (isoprenylation, proteolysis, and carboxyl methylation), membrane association, and transformation in cultured mammalian cells. While all substitutions were tolerated at the A1 position, substitutions at A2 and X reduced transforming activity. The A2 residue was important for both isoprenylation and AAX proteolysis, whereas the X residue dictated the extent and specificity of isoprenoid modification only. Differences were observed between Ras processing in living cells and farnesylation efficiency in a cell-free system. Finally, one farnesylated mutant did not undergo either proteolysis or carboxyl methylation but still displayed efficient membrane association (approximately 50%) and transforming activity, indicating that farnesylation alone can support Ras transforming activity. Since both farnesylation and carboxyl methylation are critical for yeast a-factor biological activity, the three CAAX-signaled modifications may have different contributions to the function of different CAAX-containing proteins. PMID- 1631136 TI - ADP-ribosylation factor, a small GTP-binding protein, is required for binding of the coatomer protein beta-COP to Golgi membranes. AB - The coatomer is a cytosolic protein complex that reversibly associates with Golgi membranes and is implicated in modulating Golgi membrane transport. The association of beta-COP, a component of coatomer, with Golgi membranes is enhanced by guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S]), a nonhydrolyzable analogue of GTP, and by a mixture of aluminum and fluoride ions (Al/F). Here we show that the ADP-ribosylation factor (ARF) is required for the binding of beta-COP. Thus, beta-COP contained in a coatomer fraction that has been resolved from ARF does not bind to Golgi membranes, whereas binding can be reconstituted by the addition of recombinant ARF. Furthermore, an N-terminal peptide of ARF, which blocks ARF binding to Golgi membranes, inhibits GTP[gamma S]- as well as the Al/F-enhanced binding of beta-COP. We show that Golgi coat protein binding involves a sequential reaction where an initial interaction of ARF and GTP[gamma S] with the membrane allows subsequent binding of beta-COP to take place in the absence of free ARF and GTP[gamma S]. The fungal metabolite brefeldin A, which is known to prevent the association of coat proteins with Golgi membrane, is shown to exert this effect by interfering with the initial ARF membrane interaction step. PMID- 1631137 TI - Germ-line mutations of the p53 tumor suppressor gene in patients with high risk for cancer inactivate the p53 protein. AB - Germ-line mutations in the p53 tumor suppressor gene have been observed in patients with Li-Fraumeni syndrome, brain tumors, second malignancies, and breast cancers. It is unclear whether all of these mutations have inactivated p53 and thereby provide an increased risk for cancer. Therefore, it is necessary to establish the biological significance of these germ-line mutations by the functional and structural analysis of the resulting mutant p53 proteins. We analyzed the ability of seven germ-line mutant proteins observed in patients with Li-Fraumeni syndrome, second primary neoplasms, or familial breast cancer to block the growth of malignant cells and compared the structural properties of the mutant proteins to that of the wild-type protein. Six of seven missense mutations disrupted the growth inhibitory properties and structure of the wild-type protein. One germ-line mutation retained the features of the wild-type p53. Genetic analysis of the breast cancer family in which this mutation was observed indicated that this germ-line mutation was not associated with the development of cancer. These results demonstrate that germ-line p53 mutations observed in patients with Li-Fraumeni syndrome and with second malignancies have inactivated the p53 tumor suppressor gene. The inability of the germ-line p53 mutants to block the growth of malignant cells can explain why patients with these germ-line mutations have an increased risk for cancer. The observation of a functionally silent germ-line mutation indicates that, before associating a germ-line tumor suppressor gene mutation with cancer risk, it is prudent to consider its functional significance. PMID- 1631138 TI - Localization of a DNA repair gene (XRCC5) involved in double-strand-break rejoining to human chromosome 2. AB - Complementation of the repair defect in hamster xrs mutants has been achieved by transfer of human chromosome 2 using the method of microcell-mediated chromosome transfer. The xrs mutants belong to ionizing radiation complementation group 5, are highly sensitive to ionizing radiation, and have an impaired ability to rejoin radiation-induced DNA double-strand breaks. Both phenotypes were corrected by chromosome 2, although the correction of radiation sensitivity was only partial. Complementation was achieved in two members of this complementation group, xrs6 and XR-V15B, derived independently from the CHO and V79 cell lines, respectively. The presence of human chromosome 2 in complemented clones was examined cytogenetically and by PCR analysis with primers directed at a human specific long interspersed repetitive sequence or chromosome 2-specific genes. Complementation was observed in 25/27 hybrids, one of which contained only the q arm of chromosome 2. The two noncomplementing hybrids were missing segments of chromosome 2. The use of a back-selection system enabled the isolation of clones that had lost the human chromosome and these regained radiation sensitivity. Transfer of several other human chromosomes did not result in complementation of the repair defect in XR-V15B. These data show that the gene defective in xrs cells, XRCC5, which is involved in double-strand break rejoining, is located on human chromosome 2q. PMID- 1631139 TI - Solution structure of a DNA-binding unit of Myb: a helix-turn-helix-related motif with conserved tryptophans forming a hydrophobic core. AB - The DNA-binding domain of the c-myb protooncogene product consists of three imperfect tandem repeats of 51 or 52 amino acids, each of which contains three conserved tryptophans, spaced 18 or 19 amino acids apart. The structure of the third repeat, which is essential for sequence-specific DNA binding, has been determined by NMR with distance geometry calculation. It includes three well defined helices (residues 149-162, 166-172, and 178-187) maintained by a hydrophobic core that includes the three conserved tryptophans, together with two histidines. Helices 2 and 3 form a structure related to but distinct from a canonical helix-turn-helix motif. In particular, the turn between these helices is one amino acid longer than the corresponding turn in bacterial repressors and homeodomains and contains a proline residue. In addition, the architecture of the three helices is different from those of homeodomains and DNA-binding domains of bacterial repressors. Based on the present structure, the binding mode of Myb repeat 3 with a specific DNA is also discussed. PMID- 1631140 TI - Three-dimensional scroll waves organize Dictyostelium slugs. AB - To test the hypothesis that periodic signals and chemotaxis direct later morphogenesis in Dictyostelium discoideum, we investigated cell behavior and cell movement in slugs. Trails of neutral red-stained prestalk and anterior-like cells were recorded by high-resolution digital image processing. Neutral red-stained anterior-like cells in the prespore zone of slugs move straight forward in the direction of slug migration and, furthermore, show coherent periodic cell movement. In contrast, cells in the prestalk zone move along completely different trajectories. Prestalk cells move perpendicular to the direction of slug migration; that is, they rotate around the tip. The cell movement data show that the chemotactic signal in the slug propagates as a three-dimensional scroll wave in the prestalk zone and as a planar wave in the prespore zone. The different behavior of prestalk and prespore cells is most likely caused by a difference in the oscillatory properties of the two cell types. We provide evidence that the slug stage of Dictyostelium behaves like an excitable system and that a (twisted) scroll wave organizes slug formation and migration. PMID- 1631141 TI - Platelet activation by simultaneous actions of diacylglycerol and unsaturated fatty acids. AB - Several cis-unsaturated fatty acids such as oleic, linoleic, linolenic, eicosapentaenoic, and docosahexaenoic acids added directly to intact human platelets greatly enhance protein kinase C activation as judged by the phosphorylation of its specific endogenous substrate, a 47-kDa protein. This enhancement absolutely requires the presence of a membrane-permeant diacylglycerol, 1,2-dioctanoylglycerol, or a tumor-promoting phorbol ester, phorbol 12-myristate 13-acetate. In the presence of ionomycin and either 1,2 dioctanoylglycerol or phorbol 12-myristate 13-acetate, the release of serotonin from the platelets is also remarkably increased by cis-unsaturated fatty acids. The effect of these fatty acids is observed at concentrations less than 50 microM. Saturated fatty acids and trans-unsaturated fatty acids are inactive. Titration of ionomycin to induce a release reaction and measurement of the intracellular Ca2+ level by the fura-2 procedure indicate that cis-unsaturated fatty acids increase an apparent sensitivity of the platelet response to Ca2+. The results suggest that cis-unsaturated fatty acids, which are presumably produced from phosphatidylcholine by signal-dependent activation of phospholipase A2, may take part directly in cell signaling through the protein kinase C pathway. PMID- 1631142 TI - Role of lysophosphatidylcholine in T-lymphocyte activation: involvement of phospholipase A2 in signal transduction through protein kinase C. AB - 2-Lysophosphatidylcholine (lysoPtdCho), a product of the hydrolysis of phosphatidylcholine catalyzed by phospholipase A2, greatly potentiates the activation of human resting T lymphocytes that is induced by a membrane-permeant diacylglycerol plus a calcium ionophore, as determined by the expression of the alpha subunit of the interleukin 2 receptor and thymidine incorporation into DNA. LysoPtdCho per se is inactive unless both diacylglycerol and a calcium ionophore are present. This effect of lysoPtdCho is also observed when diacylglycerol is replaced by a tumor-promoting phorbol ester. Other lysophosphatides including lysophosphatidylserine, lysophosphatidylinositol, and lysophosphatidic acid are inert except for lysophosphatidylethanolamine, which is far less effective than lysoPtdCho. Tracer experiments with radioactive choline indicate that, when T lymphocytes are stimulated with an antigenic signal, lysoPtdCho is indeed produced in a time-dependent fashion, although the concentration of this lysophospholipid accumulated remains to be quantitated. It suggests that phospholipase A2 is directly involved in the signal transduction pathway through protein kinase C to induce long-term cellular responses. PMID- 1631143 TI - Molecular basis of AMP deaminase deficiency in skeletal muscle. AB - AMP deaminase (AMPD; EC 3.5.4.6) is encoded by a multigene family in mammals. The AMPD1 gene is expressed at high levels in skeletal muscle, where this enzyme is thought to play an important role in energy metabolism. Deficiency of AMPD activity in skeletal muscle is associated with symptoms of a metabolic myopathy. Eleven unrelated individuals with AMPD deficiency were studied, and each was shown to be homozygous for a mutant allele characterized by a C----T transition at nucleotide 34 (codon 12 in exon 2) and at nucleotide 143 (codon 48 in exon 3). The C----T transition at codon 12 results in a nonsense mutation predicting a severely truncated AMPD peptide. Consistent with this prediction, no immunoreactive AMPD1 peptide is detectable in skeletal muscle of these patients. This mutant allele is found in 12% of Caucasians and 19% of African-Americans, whereas none of the 106 Japanese subjects surveyed has this mutant allele. We conclude from these studies that this mutant allele is present at a sufficiently high frequency to account for the 2% reported incidence of AMPD deficiency in muscle biopsies. The restricted distribution and high frequency of this doubly mutated allele suggest it arose in a remote ancestor of individuals of Western European descent. PMID- 1631144 TI - Viral RNA annealing activities of human immunodeficiency virus type 1 nucleocapsid protein require only peptide domains outside the zinc fingers. AB - The nucleocapsid (NC) of human immunodeficiency virus type 1 consists of a large number of NC protein molecules, probably wrapping the dimeric RNA genome within the virion inner core. NC protein is a gag-encoded product that contains two zinc fingers flanked by basic residues. In human immunodeficiency virus type 1 virions, NCp15 is ultimately processed into NCp7 and p6 proteins. During virion assembly the retroviral NC protein is necessary for core formation and genomic RNA encapsidation, which are essential for virus infectivity. In vitro NCp15 activates viral RNA dimerization, a process most probably linked in vivo to genomic RNA packaging, and replication primer tRNA(Lys,3) annealing to the initiation site of reverse transcription. To characterize the domains of human immunodeficiency virus type 1 NC protein necessary for its various functions, the 72-amino acid NCp7 and several derived peptides were synthesized in a pure form. We show here that synthetic NCp7 with or without the two zinc fingers has the RNA annealing activities of NCp15. Further deletions of the N-terminal 12 and C terminal 8 amino acids, leading to a 27-residue peptide lacking the finger domains, have little or no effect on NC protein activity in vitro. However deletion of short sequences containing basic residues flanking the first finger leads to a complete loss of NC protein activity. It is proposed that the basic residues and the zinc fingers cooperate to select and package the genomic RNA in vivo. Inhibition of the viral RNA binding and annealing activities associated with the basic residues flanking the first zinc finger of NC protein could therefore be used as a model for the design of antiviral agents. PMID- 1631145 TI - Targeting antiretroviral nucleoside analogues in phosphorylated form to macrophages: in vitro and in vivo studies. AB - A number of nucleoside analogues are active against the infectivity of human immunodeficiency virus (HIV); however, their use is limited by toxic side effects and by limited phosphorylation in the infected cells. In an attempt to overcome these problems, a drug delivery system has been developed. A prototype of these drugs in a form already phosphorylated (2',3'-dideoxycytidine 5'-triphosphate; ddCTP) was encapsulated into erythrocytes. Subsequently, by the addition of Zn, an arrangement of band 3 in clusters was induced (band 3 is the major transmembrane protein in erythrocytes). The immune system recognizes these clusters as nonself, promoting autologous IgG binding and phagocytosis by cells of the monocyte-macrophage lineage. In this way, ddCTP encapsulated into erythrocytes was delivered to macrophage cells, where concentrations greater than 2 microM were found. Addition of ddCTP-loaded erythrocytes to macrophages previously infected by HIV-1 results in almost complete inhibition of HIV production over 3 weeks in culture. Administration of ddCTP-loaded erythrocytes to LP-BM5-infected mice at 10-day intervals over a period of 3 months results in reduction of lymphoadenopathy, splenomegaly, and hypergammaglobulinemia. Thus, the delivery of nucleoside analogues in phosphorylated form is feasible, and selective targeting to virus reservoirs (macrophage cells) can be accomplished by the use of autologous erythrocytes. PMID- 1631146 TI - Adenovirus-mediated transfer of a recombinant human alpha 1-antitrypsin cDNA to human endothelial cells. AB - To evaluate the feasibility of using a replication-deficient recombinant adenovirus to transfer human genes to the human endothelium, human umbilical vein endothelial cells were infected in vitro with adenovirus vectors containing the lacZ gene or a human alpha 1-antitrypsin (alpha 1AT) cDNA. After in vitro infection with the lacZ adenovirus vector, cultured endothelial cells expressed beta-galactosidase. In parallel studies with the alpha 1AT adenovirus vector, infected cells expressed human alpha 1AT transcripts, as evidenced by in situ hybridization and Northern analysis, and de novo synthesized and secreted glycosylated, functional alpha 1AT within 6 hr of infection, as shown by [35S]methionine labeling and immunoprecipitation. Quantification of the culture supernatants demonstrated 0.3-0.6 micrograms of human alpha 1AT secreted per 10(6) cells in 24 hr, for at least 14 days after adenovirus vector infection. To demonstrate the feasibility of direct transfer of genes into endothelial cells in human blood vessels, lacZ or alpha 1AT adenovirus vectors were placed in the lumen of intact human umbilical veins ex vivo. Histologic evaluation of the veins after 24 hr demonstrated transfer and expression of the lacZ gene specifically to the endothelium. alpha 1AT adenovirus infection resulted both in expression of alpha 1AT transcripts in the endothelium and in de novo synthesis and secretion of alpha 1AT. Quantification of alpha 1AT in the vein perfusates showed average levels of 13 micrograms/ml after 24 hr. These observations strongly support the feasibility of in vivo human gene transfer to the endothelium mediated by replication-deficient adenovirus vectors. PMID- 1631147 TI - Plausible structure of the iron-molybdenum cofactor of nitrogenase. AB - A plausible structure of the iron-molybdenum cofactor of nitrogenase [reduced ferredoxin:dinitrogen oxidoreductase (ATP-hydrolyzing), EC 1.18.6.1] is presented based on altered substrate reduction properties of dinitrogenase containing homocitrate analogs within the cofactor. Alterations on each carbon of the four carbon homocitrate backbone were correlated with altered substrate reduction properties of dinitrogenase containing these analogs. Altered substrate reduction properties are the basis for a model in which homocitrate is oriented about two cubane metal clusters. PMID- 1631148 TI - The synapsis event in the homologous pairing of DNAs: RecA recognizes and pairs less than one helical repeat of DNA. AB - A key step in homologous recombination is the alignment and pairing of homologous DNAs. The Escherichia coli RecA protein initiates pairing by binding to single strand DNA, forming a helical nucleoprotein filament. We demonstrate that in the presence of the nonhydrolyzable ATP analogue adenosine 5'-[gamma thio]triphosphate and ADP, RecA can pair a homologous oligonucleotide 15 bases long with a duplex DNA to yield synaptic complexes consisting of the oligonucleotide and duplex DNA stabilized by RecA. RecA can pair as few as eight bases of homology to form such synaptic complexes. The homologous DNAs remain paired to each other upon removal of RecA provided that the length of shared homology is at least 26 base pairs. Based on our findings and the work of others, we propose that in vitro, one helical turn of a RecA nucleoprotein filament containing approximately six RecA monomers and 15 bases of single-strand DNA is the functional unit sufficient to carry out the homology search. PMID- 1631149 TI - Induced polypeptides associated with filarial worm refractoriness in Aedes aegypti. AB - Brugia malayi and Wuchereria bancrofti are mosquito-borne parasitic nematodes responsible for lymphatic filariasis in approximately 90 million people. The genetic control of the susceptibility of Aedes aegypti mosquitoes to B. malayi was well defined 30 years ago, but no data have since been provided regarding the gene products responsible for susceptibility or refractoriness or both. We addressed this problem by assessing polypeptide synthesis in thoracic tissue, the developmental site of this parasite, in susceptible and refractory strains of A. aegypti. Polyacrylamide gel electrophoresis of radiolabeled polypeptides synthesized in vivo were compared between (i) established susceptible and refractory strains and (ii) a refractory strain newly isolated from the established susceptible strain. Six polypeptide differences recognized by SDS/PAGE and two-dimensional gel electrophoresis were seen only in the refractory strains after they took a blood meal. A seventh polypeptide was present in those refractory mosquitoes that had ingested sucrose but increased in intensity after blood-feeding. The presence of parasites in the blood meal was not necessary to stimulate the synthesis of these polypeptides. These refractory strain-associated molecules may mediate genetically determined variation in susceptibility. PMID- 1631150 TI - Identification of murine homologues of the Drosophila son of sevenless gene: potential activators of ras. AB - Several findings suggest that signals from tyrosine kinases are transduced, at least in part, through ras proteins. These findings include (i) blockage of the transforming activity of constitutively active tyrosine kinases by inhibiting ras function and (ii) genetic screens in Caenorhabditis elegans and in Drosophila that identified ras genes as downstream effectors of tyrosine kinases. The recently isolated Drosophila gene Son of sevenless (Sos) is postulated to act as a positive regulatory link between tyrosine kinase and ras proteins by catalyzing exchange of GDP for GTP on ras protein. Such exchange proteins have been reported in extracts of mammalian cells but have not been previously characterized at a molecular level. As Sos appears to function in this role in Drosophila, we sought to isolate a vertebrate counterpart(s). We have characterized two widely expressed murine genes with a high degree of homology to Sos. Hybridization with human DNA and RNA indicates a high degree of conservation of these genes in other vertebrates. PMID- 1631151 TI - An infrequent point mutation of the p53 gene in human nasopharyngeal carcinoma. AB - Point mutations in the p53 gene have been detected in a variety of human cancers; the mutations are clustered in four "hot-spots" located in the coding region of exons 5, 7, and 8, which coincide with the four most highly conserved regions of the gene. We report the finding of a heterozygous G----C mutation at codon 280 (exon 8), position 2, of the p53 gene in a nasopharyngeal carcinoma (NPC) cell line, originating from Guangdong, a province in the People's Republic of China that leads the world in NPC incidence. A survey of nasopharyngeal tissues and NPC biopsies revealed that 1 out of 12 NPC samples from Hunan, another province in the People's Republic of China with high NPC incidence, had the same heterozygous mutation at codon 280 of p53, and none of 10 biopsies from Taiwan showed a mutation within exons 5-8 of the p53 gene. No other alteration of gene structure, including gross rearrangement or loss of heterozygosity or abnormality of gene expression was detected in NPC cell lines or NPC biopsies. We conclude from this study that mutational or other alterations of the p53 gene are not common in nasopharyngeal carcinogenesis and that a codon-280 mutation of p53 may be involved in less than 10% of NPC cases. This result contrasts with the relatively high frequency of p53 mutations associated with several other human carcinomas and suggests the importance of other genes in NPC genesis. PMID- 1631152 TI - Modulation of adenylate cyclase toxin production as Bordetella pertussis enters human macrophages. AB - During the course of human infection, Bordetella pertussis colonizes sequential niches in the respiratory tract that include intracellular and extracellular environments. In vitro the expression of virulence factors such as the adenylate cyclase toxin is coordinately regulated by the bvg locus, which is an example of a two-component sensory transduction system. With this toxin as a reporter, enzyme activities were compared between a wild-type and an altered strain to determine whether bacterial entry into human macrophages affected gene expression. BPRU140, a strain containing an inducible expression vector, produced enzyme activity independent of bvg. Samples of the parent, the induced, and the uninduced BPRU140 were incubated individually with macrophages for 30 min. Extracellular bacteria were then killed by gentamicin. The number of viable intracellular bacteria and the internalized bacterial enzyme activity were measured over time. By 2.5 hr all samples reached a steady-state concentration of 10(5) bacteria per 10(6) macrophages. Following an initial peak of enzyme activity, adenylate cyclase values for the parent and the uninduced BPRU140 decreased to a basal level, while the values for the induced strain remained at least 3-fold greater. Therefore, compared with the persistence of enzyme in the induced strain BPRU140, the decrease in enzyme production by the parent and the uninduced BPRU140 upon entry into macrophages indicates in vivo down-modulation of gene expression. These observations support the hypothesis that sensory transduction contributes to adaptations for bacterial survival in the infected host. PMID- 1631153 TI - Temporal asymmetry in activation of Aplysia adenylyl cyclase by calcium and transmitter may explain temporal requirements of conditioning. AB - Cellular experiments have suggested that during classical conditioning of the gill and siphon withdrawal reflex of Aplysia, adenylyl cyclase may serve as a molecular site of convergence for Ca2+ and serotonin (5-hydroxytryptamine; 5-HT), the cellular representations of the conditioned and unconditioned stimuli (CS and US). We explored the possible molecular basis of the behavioral requirement that the CS and US be paired within a narrow time window and in the appropriate order. To examine the temporal interactions of brief pulses of Ca2+ and 5-HT in stimulating Aplysia neural cyclase, we used a perfused-membrane cyclase assay. When brief pulses of Ca2+ and 5-HT were paired, cyclase activation depended upon the sequence of the pulses: peak cyclase activation was greater when the Ca2+ pulse immediately preceded the 5-HT pulse. Examination of the rising phase of 5 HT stimulation suggested that a Ca2+ prepulse might accelerate the onset of activation by 5-HT, without affecting the final level of activation achieved with prolonged 5-HT exposure. The observed interactions between Ca2+ and transmitter in activating cyclase could contribute importantly to the temporal requirements of conditioning for CS-US pairing. PMID- 1631154 TI - Perceptual asymmetry in texture perception. AB - A fundamental property of human visual perception is our ability to distinguish between textures. A concerted effort has been made to account for texture segregation in terms of linear spatial filter models and their nonlinear extensions. However, for certain texture pairs the ease of discrimination changes when the role of figure and ground are reversed. This asymmetry poses a problem for both linear and nonlinear models. We have isolated a property of texture perception that can account for this asymmetry in discrimination: subjective closure. This property, which is also responsible for visual illusions, appears to be explainable by early visual processes alone. Our results force a reexamination of the process of human texture segregation and of some recent models that were introduced to explain it. PMID- 1631155 TI - Introducing mutations into the single-copy chromosomal 23S rRNA gene of the archaeon Halobacterium halobium by using an rRNA operon-based transformation system. AB - A vector-transformation system is described that permits replacement of a portion of the single rRNA operon of the archaeon Halobacterium halobium with a homologous fragment from a vector-borne gene. The vector construct contains three functional sections: (i) an entire H. halobium rRNA operon with two selective mutations in the 23S rRNA gene, the substitutions of A----G at position 1159 conferring resistance to thiostrepton and C----U at position 2471 conferring resistance to anisomycin; (ii) the complete pHSB1 plasmid from Halobacterium sp. SB3, which interferes with vector maintenance in the transformed halobacterial cells; and (iii) a segment of the pBR322 plasmid that permits vector replication in Escherichia coli. Transformation of H. halobium with the vector plasmid generates cells resistant to both anisomycin and thiostrepton that can be selected for, and discriminated from spontaneous mutants, by a two-step selection procedure. After transformation, the plasmid recombines homologously with the chromosome so that the plasmid-borne rDNA segment with resistance markers substitutes for the corresponding region of the chromosomal rRNA operon, and the transforming plasmid is lost. Eventually, this leads to a homogeneous population of the mutant ribosomes in the cell. Other mutations that are engineered in the vector-borne rRNA sequences can be transferred to the chromosomal rRNA operon concomitantly with the selective markers. The system has considerable potential for ribosomal engineering. PMID- 1631156 TI - Evolution of major histocompatibility complex class II allelic diversity: direct descent in mice and humans. AB - The high degree of polymorphism seen at major histocompatibility complex (MHC) class II loci is a feature unique to the MHC. Most of the beta-chain polymorphism is localized in "hypervariable" regions (HVRs). HVR amino acid sequence similarity between distantly related species has recently been found. We have employed a Monte-Carlo statistic to show that shared HVR polymorphism between beta-chain genes of humans and mice represents direct descent of ancestral sequences rather than convergent evolution. Furthermore, half the sequence polymorphism seen in class II beta-chain genes of mice persists in evolution and is encoded by the same DNA sequence in humans. No evidence for increased mutation rate within the HVR was found. We postulate that the HVR can be considered the genetic unit of recombination, with selection for HVR sequences and combinations of HVRs constrained by functional considerations. PMID- 1631157 TI - Cloning and chromosomal location of human alpha 1(XVI) collagen. AB - We have characterized cDNA clones that encode a newly discovered collagenous polypeptide. A 4-kilobase (kb) cDNA clone was initially isolated by screening a human fibroblast cDNA library with a probe encoding the collagenous domain of the human alpha 3(VI) collagen. Subsequent screening of another fibroblast cDNA library yielded overlapping clones having a total length of 5.4 kb, which contained an open reading frame of 1603 amino acids including a 21-amino acid signal peptide. The predicted polypeptide consists of 10 collagenous domains 15 422 amino acids long, which were interspersed with 11 noncollagenous (NC) domains. Except for a large N-terminal NC11 domain of 312 residues, most of the NC domains were short (11-39 residues) and cysteine-rich. The overall structural arrangement differed significantly from other known collagen chains. Further analysis indicated that the deduced polypeptide exhibited several structural features characteristically seen in members of the fibril-associated collagen, types IX, XII, and XIV. In addition, the cysteine-rich motifs in the NC domains resembled those found in the cuticle collagen of Caenorhabditis elegans. Northern blot analyses showed hybridization of the cDNA to a 5.5-kb mRNA in human fibroblasts and keratinocytes. The gene was localized by in situ hybridization to band p34-35 of human chromosome 1. The data clearly support the conclusion that the cDNA encodes a collagen chain that has not been previously described. We suggest that the cDNA clones encode the alpha 1 chain of type XVI collagen. PMID- 1631158 TI - Gene order comparisons for phylogenetic inference: evolution of the mitochondrial genome. AB - Detailed knowledge of gene maps or even complete nucleotide sequences for small genomes leads to the feasibility of evolutionary inference based on the macrostructure of entire genomes, rather than on the traditional comparison of homologous versions of a single gene in different organisms. The mathematical modeling of evolution at the genomic level, however, and the associated inferential apparatus are qualitatively different from the usual sequence comparison theory developed to study evolution at the level of individual gene sequences. We describe the construction of a database of 16 mitochondrial gene orders from fungi and other eukaryotes by using complete or nearly complete genomic sequences; propose a measure of gene order rearrangement based on the minimal set of chromosomal inversions, transpositions, insertions, and deletions necessary to convert the order in one genome to that of the other; report on algorithm design and the development of the DERANGE software for the calculation of this measure; and present the results of analyzing the mitochondrial data with the aid of this tool. PMID- 1631159 TI - Active nuclear import of human immunodeficiency virus type 1 preintegration complexes. AB - After cell infection by the human immunodeficiency virus type 1 (HIV-1), nascent viral DNA in the form of a high molecular weight nucleoprotein preintegration complex must be transported to the nucleus of the host cell prior to integration of viral DNA with the host genome. The mechanism used by retroviruses for nuclear targeting of preintegration complexes and dependence on cell division has not been established. Our studies show that, after infection, the preintegration complex of HIV-1 was rapidly transported to the nucleus of the host cell by a process that required ATP but was independent of cell division. Functional HIV-1 integrase, an essential component of the preintegration complex, was not required for nuclear import of these complexes. The ability of HIV-1 to use host cell active transport processes for nuclear import of the viral preintegration complex obviates the requirement for host cell division in establishment of the integrated provirus. These findings are pertinent to our understanding of early events in the life cycle of HIV-1 and to the mode of HIV-1 replication in terminally differentiated nondividing cells such as macrophages (monocytes, tissue macrophages, follicular dendritic cells, and microglial cells). PMID- 1631160 TI - Structure-function relationships of the yeast fatty acid synthase: negative stain, cryo-electron microscopy, and image analysis studies of the end views of the structure. AB - The yeast fatty acid synthase (M(r) = 2.5 x 10(6)) is organized in an alpha 6 beta 6 complex. In these studies, the synthase structure has been examined by negative-stain and cryo-electron microscopy. Side and end views of the structure indicate that the molecule, shaped similar to a prolate ellipsoid, has a high density band of protein bisecting its major axis. Stained and frozen-hydrated average images of the end views show an excellent concordance and a hexagonal ring having three each alternating egg- and kidney-shaped features with low protein-density protrusions extending outward from the egg-shaped features. Images also show that the barrel-like structure is not hollow but has a Y-shaped central core, which appears to make contact with the three egg-shaped features. Numerous side views of the structure give good evidence that the beta subunits have an archlike shape. We propose a model for the synthase that has point-group symmetry 32 and six equivalent sites of fatty acid synthesis. The protomeric unit is alpha 2 beta 2. The ends of each of the two archlike beta subunits interact with opposite sides of the two dichotomously arranged disclike alpha subunits. Three such protomeric units form the ring. We propose that the six fatty acid synthesizing centers are composed of two complementary half-alpha subunits and a beta subunit, an arrangement having all the partial activities of the multifunctional enzyme required for fatty acid synthesis. PMID- 1631161 TI - Cooperation between the products of different nuclei in hybrid myotubes produces localized acetylcholine receptor clusters. AB - Cultured myotubes form clusters of acetylcholine receptors (AChRs) spontaneously and at sites of nerve-muscle contact. To investigate the cellular mechanisms by which spontaneous clusters are formed, we have made hybrid myotubes between a mouse muscle cell variant, S27, that does not cluster AChRs, and one that does not make AChRs. We have also made hybrid myotubes using S27 and quail muscle cells. In both cases, clusters of AChRs were found near the non-S27 nuclei; in the case of the interspecific hybrids, mouse AChRs were associated with extracellular matrix components contributed by the quail nuclei. Our results suggest that AChRs made by one nucleus can be clustered by localized extracellular matrix produced by a different nucleus and provide an example of nuclear cooperation between the products of different nuclei within multinucleated muscle fibers. PMID- 1631162 TI - Interferon alpha induces the expression of retinoblastoma gene product in human Burkitt lymphoma Daudi cells: role in growth regulation. AB - Interferon alpha (IFN-alpha) is a regulatory secretory protein with distinctive biological effects such as antiproliferative actions against many tumor cell lines, including human Burkitt lymphoma Daudi cells. The mechanism underlying growth inhibition by IFN-alpha is not well established. The growth of many mammalian cell types is also regulated by tumor suppressor retinoblastoma (RB) gene product, the RB protein. In the studies presented here, we explored the possible involvement of RB protein in the growth inhibitory action of IFN-alpha in the Daudi cell model system. We observed that IFN-alpha induces a 3- to 10 fold increased expression of RB protein in growth-sensitive Daudi cells but not in the growth-resistant variant of Daudi cells. IFN-alpha-mediated induction of RB protein was an early event that preceded the period of growth inhibition of Daudi cells. IFN-alpha-induced RB protein predominantly exists as the underphosphorylated form. Addition of antibody against IFN-alpha to Daudi cells resulted in the inhibition of constitutive expression of RB protein and stimulation of [3H]thymidine incorporation. These results demonstrate that the induction of RB protein expression in IFN-alpha-treated Daudi cells could constitute an important mechanism of IFN-alpha-mediated growth regulation. PMID- 1631163 TI - Functional reconstitution of the lysosomal sialic acid carrier into proteoliposomes. AB - The lysosomal carrier for the acidic monosaccharides sialic acid and glucuronic acid was solubilized from rat liver lysosomal membranes and reconstituted into phospholipid vesicles. Membrane proteins were extracted from lysosomal membranes with Triton X-100. Upon removal of the detergent by absorption on Amberlite XAD-2 beads, the solubilized proteins were incorporated in egg yolk phospholipids. The reconstituted proteoliposomes show proton-driven carrier-mediated uptake of acidic monosaccharides. The reconstituted carrier was compared in several characteristics with the transporter as present in the native lysosomal membrane. Transporter substrate affinity (Kt for glucuronic acid = 0.4 mM) and specificity for acidic monosaccharides are completely retained. The proteoliposomes also demonstrate trans-stimulation properties with both substrates sialic acid and glucuronic acid. The transporter is inhibited, both in its native and in the reconstituted state, by the sulfhydryl-modifying agents p-chloromercuribenzoic acid, N-ethylmaleimide, and phenyl isothiocyanate. In native membrane vesicles, arginine and histidine modifiers phenylglyoxal and diethyl pyrocarbonate inactivated transport in a substrate-protectable manner. In reconstituted proteoliposomes, similar inhibition was observed. However, protection by substrates was achieved only after treatment with phenylglyoxal. These data suggest that arginine or histidine residues or both are present at or near the substrate binding site of the carrier. Possibly, other essential histidines become exposed in the reconstituted state. The successful functional reconstitution of the lysosomal sialic acid carrier represents an important step towards its purification and its detailed molecular characterization. PMID- 1631164 TI - Effects of compact volume and chain stiffness on the conformations of native proteins. AB - An investigation of the statistical properties of the native conformations of proteins, observed from crystal structures, is reported. Protein conformations were analyzed in terms of a bond vector correlation function and molecular volume. It was observed that, while the volume of a protein structure varies nearly linearly with the number of residues, the bond vector correlation function exhibits a universal feature for all sizes of proteins. To interpret the nature of the bond vector correlation function of native protein structures quantitatively, Monte Carlo simulations of realistic polypeptide chains of specific but arbitrary amino acid sequence were carried out. The molecule was constrained in an ellipsoidal volume determined by its chain length, and conformations with unacceptable nonbonded contacts between different amino acid residues were excluded. The interactions within a terminally blocked single residue, which correlate two nearest-neighbor peptide groups in a chain, were taken into account by an energetically biased sampling of its phi-psi space. The simulated chain correlation functions were found to be in good agreement with those of the crystal structures of beta-sheet-type and mixed-type (alpha+beta) proteins of similar length. On the basis of these calculations, it is concluded that the observed conformations of these native proteins may arise from two basic factors: the compactness of structures under hydrophobic interactions and the intrinsic stiffness of polypeptide chains due to the interactions within each terminally blocked residue. PMID- 1631165 TI - Endosulfine, an endogenous peptidic ligand for the sulfonylurea receptor: purification and partial characterization from ovine brain. AB - Antidiabetic sulfonylureas act through receptors coupled to ATP-dependent potassium channels. Using the binding of [3H]glibenclamide, a highly potent sulfonylurea, to rat brain membranes to follow the purification procedure, we extracted from ovine brain, purified, and partially characterized two peptides that are endogenous ligands for the central nervous system sulfonylurea receptors. These peptides, referred to as alpha and beta endosulfine, differ by their isoelectric points, the beta form being more basic. Each form of endosulfine is recognized equally by the sulfonylurea receptors from the central nervous system and from insulin-secreting beta cells. In the same concentration range that is active on the receptors, beta endosulfine releases insulin from a beta-cell line. Endosulfine is a good candidate for being implicated in the physiology of beta cells and their disorders (e.g., type II diabetes) and in certain pathologies related to modifications of ion fluxes. PMID- 1631166 TI - Mutational analysis of the human immunodeficiency virus type 1 Eli Nef function. AB - The studies presented here define an internally consistent experimental system that permits systematic analysis of the effect of nef on the rate of the human immunodeficiency virus type 1 (HIV-1) replication in a CD4+ tumor T-cell line and in primary peripheral blood mononuclear cells. The parental full-length Nef protein, derived from the Eli strain of HIV-1, accelerates virus replication in both cell types. Mutations that destabilize or alter the intracellular location of the protein affect the ability of the Nef protein to accelerate virus replication. A set of mutants was made in amino acids proposed to be required for Nef function, including threonine and serine residues proposed to be targets for phosphorylation, and in sequences thought to resemble the G-1, G-3, and G-4 sites of the family of G proteins. In most cases alterations of the critical amino acids yield stable Nef proteins of parental phenotype. These results challenge the existing theories for the mechanism of Nef function. The results also identify two residues in the carboxyl half of the protein that are important for Nef function. PMID- 1631168 TI - Crystal structure determination at 2.3-A resolution of human transthyretin-3',5' dibromo-2',4,4',6-tetrahydroxyaurone complex. AB - The crystal structure of the complex of 3',5'-dibromo-2',4,4',6 tetrahydroxyaurone, a flavone derivative, with human transthyretin (TTR), a serum thyroid hormone transport protein, has been determined and refined to R = 17.9% for data to 2.3-A resolution and provides a detailed description of a protein bound flavonoid structure. This bromoaurone is a potent competitor for thyroid hormone binding to TTR, a 54,980-dalton alpha 4 tetrameric protein of 222 molecular symmetry, as well as an inhibitor of iodothyronine deiodinase. Crystals of the TTR-bromoaurone complex are isomorphous to those of native TTR. Interpretation of difference Fourier electron density maps revealed two binding modes for the bromoaurone in each of the two independent binding sites of the TTR tetramer: deep in the channel near Ser-117 (mode I) and near the channel entrance (mode II). None of the binding modes can be fully occupied because of overlap between binding positions. A statistical disorder for bromoaurone binding was also applied, as it binds along the twofold crystallographic axis and does not possess such symmetry. The binding of mode I and that of mode II were refined at half occupancy, resulting in two molecules per tetramer. The bromoaurone binds in a nonplanar antiskewed conformation. The molecular pattern for TTR binding consists of halogen groups able to anchor between beta-sheets to form both hydrophobic and hydrophilic contacts. Comparison of structural data for bromoaurone- and thyroxine-TTR complexes indicates that bromoaurone binding mode I is 3 A deeper in the channel and binding mode II is 4 A further from the channel center than thyroxine. The bromoaurone binding observed in this TTR complex differs significantly from that based upon computer modeling studies. PMID- 1631167 TI - A family of genes encoding neurotransmitter transporters. AB - The genomic and cDNA clones of the mouse gamma-aminobutyric acid transporter were sequenced and analyzed. The genomic clone contains 12 introns including 1 intron prior to the initiator methionine. The second intron comes immediately after the stretch of amino acids that is most conserved among the neurotransmitter transporters sequenced so far. By using a probe constructed according to this conserved region, several partial genomic clones were isolated. Sequence analysis of those clones reveals not only homology to the family of neurotransmitter transporters within the reading frame but also an identical location of an exon intron junction after the conserved region. A search of the GenBank data base (April 1991) revealed that two invertebrate genes exhibit homology to the conserved sequence of the above family. One, a Drosophila melanogaster gene, encoded the N-terminal part of a protein homologous to neurotransmitter transporters and the second was in Caenorhabditis elegans. The Drosophila gene contains an intron that starts at a position identical to the corresponding positions of all the mammalian genes of the family. PMID- 1631170 TI - Neural-specific expression, genomic structure, and chromosomal localization of the gene encoding the zinc-finger transcription factor NGFI-C. PMID- 1631169 TI - Identification of a family of bacteriophage T4 genes encoding proteins similar to those present in group I introns of fungi and phage. AB - The bacteriophage T4 segA gene lies in a genetically unmapped region between the gene beta gt (beta-glucosyltransferase) and uvsX (recombination protein) and encodes a protein of 221 amino acids. We have found that the first 100 amino acids of the SegA protein are highly similar to the N termini of four other predicted T4 proteins, also of unknown function. Together these five proteins, SegA-E (similar to endonucleases of group I introns), contain regions of similarity to the endonuclease I-Tev I, which is encoded by the mobile group I intron of the T4 td gene, and to putative endonucleases of group I introns present in the mitochondria of Neurospora crassa, Podospora anserina, and Saccharomyces douglasii. Intron-encoded endonucleases are required for the movement (homing) of the intron DNA into an intronless gene, cutting at or near the site of intron insertion. Our in vitro assays indicate that SegA, like I-Tev I, is a Mg(2+)-dependent DNA endonuclease that has preferred sites for cutting. Unlike the I-Tev I gene, however, there is no evidence that segA (or the other seg genes) resides within introns. Thus, it is possible that segA encodes an endonuclease that is involved in the movement of the endonuclease-encoding DNA rather than in the homing of an intron. PMID- 1631171 TI - [The importance of digestive tract lipases in the hydrolysis of lipid excipients and substitution enzyme therapy. Part 1]. PMID- 1631172 TI - [The effect of two lubricants (magnesium stearate and pruv) in the formation of tablets of four anti-ulcer agents/ by means of direct compression]. AB - In this research we study the influence of two lubricants-Magnesium Stearate and Pruv--on the tablets elaboration of Cimetidine, Ranitidine, Famotidine and Pirenzepine by direct compression. The presence of 0.5% of lubricants improved the flow of all the formulations, but especially the Famotidine's formulation. The formulations with Magnesium Stearate had the worst results in tests of friability and tensile strength. All tablets with drugs and Pruv had high data in indentation hardness. The tablets of Cimetidine, Famotidine and Pirenzepine with Magnesium Stearate had less time of disintegration. PMID- 1631173 TI - Monthly prostaglandin bibliography prepared by the University of Sheffield Biomedical Information Service. PMID- 1631174 TI - Urinary prostanoid excretion in healthy women with different degrees of induced potassium depletion. AB - Plasma renin activity (PRA), urinary excretions of PGE2, 6-keto-PGF1 alpha (6KPGF), TXB2 and renal function were determined in healthy women both in normal potassium balance (N, n = 14) and in experimental potassium depletion (KD). KD was induced by natriuretic treatment--associated to replacement of net NaCl and water losses--in the presence of either normal (congruent to 50 mmol/d) or low (less than or equal to 10 mmol/d) dietary potassium intake. By using different depletive patterns, three groups with estimated cumulative potassium deficit (mean +/- SEM) of 124 +/- 38 (KD0, n = 8), 160 +/- 43 (KD1, n = 8) and 198 +/- 22 mmol (KD2, n = 6), respectively, were obtained. Renal function by the clearance (cl.) method and urinary prostanoid concentrations by the RIA method were estimated during hypotonic polyuria (oral water load) and subsequent moderate antidiuresis induced by a low-dose infusion of lysine-8-vasopressin. 1. In KD0 group the potassium depletive treatment was inefficacious in significantly reducing either the plasma potassium concentration (PK) or the urinary potassium excretion (UKV). The reductions of PK and UKV as well as the enhancement of PRA became significant in KD1 and KD2 groups. 2. The urinary prostanoid excretions were not significantly changed in the KD0 and KD1 groups while in the KD2 group they were reduced, mainly concerning the urinary 6KPGF excretion. 3. Furthermore in the KD2 group, with larger potassium depletion, some of the typical hypokalemic renal dysfunctions appeared. The data suggest that a pathophysiologically critical degree of potassium depletion is associated with an inhibited renal prostanoid synthesis as well as an increased renin secretion. PMID- 1631175 TI - Influence of leukotriene D4 on arterial pressure and gastrointestinal electrical activity in the conscious piglet. AB - In 6 conscious weaned piglets with implanted electrodes in the corpus and antrum of the stomach, the duodenum, jejunum, ileum and caecum the influence of intravenous infusion of leukotriene (LT)D4, 0.1 and 1 microgram kgmin for 10 min, on mean arterial pressure and gastrointestinal electrical activity was examined. LTD4 induced a significant increase in arterial pressure. Gastrointestinal electrical activity, however, was little influenced, since only the antrum pylori revealed a transient decrease. PMID- 1631176 TI - Increased concentrations of phosphatidylinositol (PI) and decreased esterification of arachidonic acid into phospholipids in platelets from patients with schizoaffective disorders or atypic phasic psychoses. AB - The concentration of various phospholipids (PLs) and sphingomyelin in platelets and the amount of [14C] arachidonic acid ([14C]-AA) esterified in phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidylcholine (PC) were measured. The platelet-rich plasmas from unmedicated patients with psychiatric disorders and healthy controls were incubated for 30 min with 1 microM [14C]-AA. Platelets from patients with a schizoaffective disorder according to RDC criteria, a schizophreniform disorder (DSM III criteria) or an atypical phasic psychosis according to FC criteria contained twice as much PI and had significantly increased concentrations of PC as compared to controls (p less than 0.05, t-test). A highly significant (40-70%) reduced rate of esterification of [14C]-AA into PI/PS, PC and PE was found in platelets from patients with schizophreniform, schizoaffective and major depressive disorders but not in platelets from patients with chronic schizophrenia. The largest reduced esterification of [14C]-AA (about 70%) was found in PI/PS of platelets from patients with schizoaffective disorders (1.9 +/- 0.7 vs 6.3 +/- 1.7 mumol [14C]-AA/mol PI/PS; p less than 10(-4), t-test). The results indicate that changes in the metabolism of arachidonic acid and phosphatidylinositol and, to a lesser degree, of phosphatidylcholine in platelets are characteristic of patients with a likely favorable outcome of a psychotic episode. PMID- 1631177 TI - Mechanical injury increases eicosanoid production in cultured cardiomyocytes. AB - The release of three stable metabolites of the arachidonic acid cascade was determined in cultures of cardiac myocytes and of non-muscle cells. In both cell types, the main product was 6-keto-PGF1 alpha much less PGE2 was released, while TXB2 was only detected in muscle cells. Preincubation with arachidonic acid increased the release of all the PGs in both types of culture. Mechanical injury had a synergistic effect on the increased PG release in AA-preincubated cells. However, TXB2 was not detected in F-cells in any experimental conditions. These results suggest that PG production serves a functional role in heart preservation during injury. PMID- 1631178 TI - Effect of adenosine analogues on the expression of opiate withdrawal in rats. AB - The aim of this study was to test whether convergent dependence occurs in vivo. The adenosine A1 receptor agonist N6-[(R)-1-methyl-2-phenylethyl]adenosine (R PIA), the A2 agonist 2-(phenylamino)adenosine (CV-1808), the nonselective A1, A2 agonist (adenosine-5'-ethylcarboxamide (NECA), and the alpha 2-adrenoceptor agonist clonidine were screened (each at 30, 100, and 300 micrograms/kg, SC) for their ability to alter naloxine-precipitated withdrawal signs in morphine dependent rats. The results indicate that there is convergent dependence involving opioid and adenosine A1 receptors on those effects expressed by withdrawal diarrhoea, paw-shakes, teeth-chattering, body-shakes, and jumping. Further, dependence expressed by body-shakes involves convergence involving A1 receptors, as well as alpha 2-adrenoceptors; while A1 receptors are involved in dependence expressed by jumping, stimulation of alpha 2-adrenoceptors augments this sign. Adenosine analogues may be of clinical value for detoxification of opiate addicts. PMID- 1631180 TI - Strain-specific alterations in consumption of a palatable diet following repeated stressor exposure. AB - Exposure to acute inescapable shock caused reductions in the consumption of a highly palatable diet. The magnitude and duration of the reduction varied across strains of mice. With repeated exposure to footshock, consumption of the diet returned to baseline levels, although alterations of weight appeared to be more persistent. The course of the adaptation varied across strains of mice; however, the rate of adaptation was unrelated to the extent of the alterations of consumption induced by the acute stressor. When mice were exposed to a series of different stressors, the adaptation progressed less readily, and reductions of diet consumption were apparent in strains that had not shown such an effect following acute stressor application or when repeatedly exposed to a single type of stressor. Data were discussed with respect to the mechanisms that might be operative in subserving stressor-induced anhedonia. PMID- 1631179 TI - Effects of neuropeptide Y on food-reinforced behavior in satiated rats. AB - The effect of NPY on behavior and food intake of food-satiated rats was examined under three different food availability conditions. Food was available during times when rats normally do not eat under either a fixed-ratio or fixed-interval reinforcement schedule, or it was freely available in the bottom of the cage (FF). Forty responses were required for each 45-mg food pellet under the ratio schedule (FR 40) and for the first response to occur 15 s after the previous reinforcement under the interval schedule (FI 15"). NPY (5 micrograms) significantly increased food intake under all conditions and increased food reinforced responses under the FR and FI schedules. NPY's effect on food intake was greatest when food was freely available and least for rats working under the schedule requiring the most effort (FR 40). Food intake peaked after 3 days under repeated daily administration of NPY. Under free food access and under the fixed interval schedule, eating and/or responding occurred almost immediately following the onset of the initial 4-h session under NPY. However, during the first session following NPY administration under the FR, rats emitted few responses during the first 2 h of the session. The onset of robust responding under the FR schedule began earlier with each successive daily administration of NPY. These data show NPY substantially increases food-maintained behavior and is a potent inducer of food intake even under conditions where considerable effort is required to obtain food. Further, the conditions under which food is made available can dramatically alter NPY's effect on the temporal pattern of food-maintained responding, feeding, and latency to eat. PMID- 1631181 TI - Active avoidance behavior in guinea pigs: effects of physostigmine and scopolamine. AB - Behavioral training of guinea pigs by conventional methods, such as used for rats and mice, appears difficult. Hence, only a few behavioral experiments with guinea pigs have been described in the literature. An active avoidance technique in an automated two-way shuttlebox is described using sound as a conditioned (CS) and a tactile stimulus (a stream of air ruffling their fur) as an unconditioned (UCS) stimulus. Acquisition is fairly rapid and reproducible. Doses of physostigmine that caused moderate blood acetylcholinesterase inhibition induced dose-dependent performance decrements. These decrements were counteracted by a sign-free dose of scopolamine. PMID- 1631182 TI - Differential effects of CCK-JMV-180 on food intake in rats and mice. AB - Boc-Tyr(SO3)-Nle-Gly-Trp-Nle-Asp-2-phenylether ester (CCK-JMV-180) has been reported to be a CCK-based heptipeptide with novel in vitro properties. Based on studies conducted in rat and mouse pancreatic acini, it has been proposed that the compound acts as an agonist at the high-affinity site and an antagonist at the low-affinity site in the rat, but as an agonist at both sites in the mouse. In the present study, we examined the effects of CCK-JMV-180 on locomotor activity in the rat and on intake of a liquid diet in the rat and mouse. Although CCK-JMV-180 slightly reduced activity on its own in the rat, it completely reversed the suppression produced by coadministration of CCK-8. In rat feeding studies, CCK-JMV-180 failed to suppress intakes of a liquid diet, but was able to antagonize the anorectic effects of CCK-8. In contrast, in the mouse CCK-JMV-180 potently suppressed intakes on its own, and this effect was blocked by pretreatment with the selective CCK-A receptor antagonist, A-70104. The results of these studies suggest that similar receptor mechanisms are involved in CCK's ability to inhibit food intake in vivo and its effects on pancreatic function in vitro. PMID- 1631183 TI - Repeated administration of diazepam reduces [3H]Ro 5-4864 binding in cerebral cortex of rats. AB - Binding of [3H]Ro 5-4864 to mitochondrial membrane preparations of rat cerebral cortex was measured after repeated (5 days) IV administration of diazepam (10 mg/kg daily) and clonazepam (2.5 mg/kg daily). The B(max) value for [3H]Ro 5-4864 was significantly reduced in rats treated with diazepam (-49%) but not in those treated with clonazepam. These findings suggest the involvement of peripheral type binding sites in the development of rapid tolerance to the sedative effects of benzodiazepines. A downregulation of [3H]Ro 5-4864 (-65%) was also observed after repeated administration of Ro 5-4864 (4 mg/kg daily), thus confirming that this compound behaves as an agonist at its own recognition sites. PMID- 1631184 TI - "Paradoxical" effects of smoking on subjective stress versus cardiovascular arousal in males and females. AB - Cigarette smoking has sometimes been found to decrease subjective stress while simultaneously increasing cardiovascular arousal, contrasting effects referred to as the "nicotine paradox." The present study assessed acute effects of cigarette smoking on subjective stress vs. cardiovascular arousal in minimally deprived male and female smokers who smoked (n = 16) or sham smoked (unlit cigarette, n = 15) and a comparison group of male and female nonsmokers (n = 12) who sham smoked only. All subjects participated in two sessions (high- or low-challenge computer task) in which they smoked or sham smoked prior to each of two 20-min task trials. Results showed reduced subjective stress in smoking smokers compared with sham-smoking smokers during the high- but not low-challenge task. However, this stress reduction occurred only immediately after smoking and dissipated midway through each trial. In males, smoking appeared to reduce stress below that of nonsmokers, while smoking in females attenuated stress only partially to the level of nonsmokers. In contrast with the attenuated stress effects, cardiovascular arousal (especially heart rate) was increased immediately after smoking during both tasks and did not appear to be directly related to subjective changes. These findings suggest that the stress-reducing effects of smoking may be transient, situationally specific, partly gender dependent, and dissociated from the effects of smoking on cardiovascular arousal. PMID- 1631185 TI - Limbic forebrain toxin trimethyltin reduces behavioral suppression by clonidine. AB - Trimethyltin (TMT) at moderate doses selectively damages hippocampus and related olfactory cortex and produces learning and memory impairments. TMT also increases forebrain beta-adrenergic ligand binding; this could be ancillary to reduced noradrenergic neurotransmission, which in turn could be involved in the cognitive deficit caused by TMT. If this hypothesis is correct, then the alpha 1-adrenergic agonist clonidine, which inhibits noradrenergic neurotransmission in normal subjects, should be less behaviourally effective after TMT poisoning. Thus, rats treated with water vehicle or TMT (6 mg/kg, PO) were given saline or clonidine IP (5, 10, or 20 micrograms/kg) 30 min before placement in a hole-board apparatus. Exploratory activity was reduced in controls by 10 or 20 micrograms/kg. Clonidine at 10 micrograms/kg was ineffective in rats given TMT. At 20 micrograms/kg, an apparent reduction in exploratory activity was not significant because variability of responding was higher after TMT treatment. The results suggest an impairment in noradrenergic neurotransmission following TMT poisoning. PMID- 1631186 TI - Test-specific effects of FG-7142 on isolation-induced aggression in mice. AB - Treatment with FG-7142 decreased isolation-induced attack, but not defense, by male mice when the residents' home cages contained only a sawdust substrate. When a small wooden nesting box was added to the cage (Experiment 2), however, FG-7142 somewhat increased levels of attack. Time spent in the nesting box was also increased, while overall levels of social interaction were decreased, by drug treatment in Experiment 2. The latter findings are consistent with FG-7142's well documented anxiogenic properties and indicate that this drug is probably proaggressive in its actions. The antiaggressive effects of FG-7142 in Experiment 1 may have resulted from drug-induced fear behaviors that were incompatible with attack. Alternatively, Experiment 2 suggests the possibility that species-typical attack may be defensively motivated under some circumstances. Although the antiagressive properties of eltoprazine and yohimbine were unaffected by the addition of the nest box (Experiment 3), the provision of some sort of refuge within the testing apparatus may be an important methodological consideration for studies employing resident-intruder paradigms. PMID- 1631187 TI - Opiate effect on the threat display in the crab Carcinus mediterraneus. AB - The well-known defense response of a crab (laterus merus display, LMD) was easily evoked in Carcinus mediterraneus by striking the cephalothoraxic protogastric region between the eyestalks. Following a program aimed at investigating the regulatory action of diverse neuromodulators on the LMD of this crab, a study on the role of opioids was started by testing the effect of morphine administration. Injection of morphine HC1 (MP) (40, 50, 60, 70, or 100 micrograms/g) produced a dose-dependent reduction of the LMD so elicited that dissipated with the postinjection time. Only MP doses higher than 50 micrograms/g were effective 30 min after drug administration. The MP-induced inhibition of LMD was blocked by a 4.8-micrograms naloxone HC1/g dose injected 10 min before MP. These results and those previously obtained as the action of GABA on the LMD of this crab are discussed in connection with results reporting a similar effect of these drugs on another agonistic item of behavior in the crab Chasmagnatus granulatus. The possibility of demonstrating habituation of the LMD to an iterated stimulation in C. mediterraneus and of using such a process to elucidate the acting paths of the drugs is discussed. PMID- 1631188 TI - Effects of smoking abstinence and chain-smoking on puffing topography and diurnal nicotine exposure. AB - Effects of chain-smoking, a 15-h smoking abstinence, and the nicotine yield of cigarettes on puff indices were studied in eight healthy smokers by using a controlled crossover study design. Puff parameters were measured puff by puff with a portable measuring device when 10 or 20 cigarettes, with nicotine yields of 0.3 and 1.0 mg, were smoked per day. The interval between sessions was 1 h, and the 20 cigarettes per day were chain-smoked 2 at a time. Serum cotinine indicated that smokers compensate completely for the lower nicotine delivery from the 0.3-mg cigarette. Smokers almost doubled total puff volume per cigarette and per day mainly by taking more puffs from the low-nicotine cigarettes and slightly prolonging puff duration. However, nicotine deprivation and chain-smoking had a relatively minor effect on puffing indices with both brands, a fact that agrees poorly with the nicotine titration hypothesis. However, in the course of every single cigarette of the day smokers significantly reduced puff duration and puff volume toward the end of the cigarette, which probably involves satiation of the nicotine crave but may also be due to changes in taste of the smoke. PMID- 1631189 TI - Acute effects of chlorpromazine in a monkey operant behavioral test battery. AB - The effects of acute chlorpromazine treatment were assessed using a complex operant test battery (OTB) containing five tasks thought to depend upon processes associated with short-term memory and attention [delayed-matching-to-sample (DMTS)], color and position discrimination [conditioned position responding (CPR)], motivation [progressive ratio (PR)], time perception [temporal response differentiation (TRD)], and learning [incremental repeated acquisition (IRA)]. Adult male rhesus monkeys were tested 15 min after IV injection of saline or chlorpromazine (0.010, 0.030, 0.100, or 0.175 mg/kg). Behavioral endpoints measured included percent task completed, response rate or latency, and response accuracy. The order of task sensitivity to disruption by chlorpromazine was TRD = PR = IRA = DMTS = CPR in which sensitivity was defined as a significant alteration in any aspect of task performance. Chlorpromazine slowed response rates in all tasks except TRD but did decrease accuracy in that task. These effects were similar to those noted in previous studies of acute chlorpromazine treatment. Specific motoric effects suggested decreased task initiation at doses that left general motor ability intact. This finding is similar to that noted in parkinsonism caused by chronic chlorpromazine treatment. PMID- 1631190 TI - Novel approach to diet design for determining macronutrient preference. AB - Previous studies indicate that rats fed a saturated vs. unsaturated fat consume more of a high-protein/low-carbohydrate and less of a low-protein/high carbohydrate diet. Present studies were conducted to determine whether saturated fat-fed rats are preferring protein or avoiding carbohydrate. Three combinations of diets were prepared in which one macronutrient was held constant and two covaried: 1) high protein/low carbohydrate and low protein/high carbohydrate, 2) high fat/low carbohydrate and low fat/high carbohydrate, and 3) high fat/low protein and low fat/high protein. Male Sprague-Dawley rats (75-99 g) were fed either 34% tallow (n = 30) or corn oil (n = 30) diets for 4 days. These diets were removed and one third of each group was given one of the diet combinations. Rats previously fed tallow consumed more high-protein/low-carbohydrate and low carbohydrate/high-fat diets and less high-carbohydrate/low-fat diet than controls previously fed corn oil. These data suggest that tallow-fed animals are avoiding carbohydrate rather than preferring protein. PMID- 1631191 TI - Ketamine retards chronic but not acute tolerance to ethanol. AB - Motor impairment (tilt-plane test) was used to investigate whether the noncompetitive N-methyl-D-aspartate (NMDA) antagonist ketamine prevents the development of chronic and acute tolerance to ethanol. Rats were treated with ethanol or saline in the presence and absence of ketamine (separate groups) for 10 days and tested for ethanol tolerance in the absence of ketamine on the fifth and tenth days. In other studies, the effect of ketamine on acute tolerance to ethanol was examined. Rats that received ethanol daily without ketamine showed significant tolerance to ethanol on days 5 and 10, but those receiving ethanol plus ketamine daily showed significantly less tolerance to ethanol. Thus, ketamine interfered with the development of chronic tolerance just as it had been found previously to prevent rapid tolerance. In contrast, ketamine failed to block acute tolerance to ethanol. These results would suggest that the phenomena of acute tolerance and chronic tolerance have differences not previously reported. PMID- 1631192 TI - Human visual perception and ROC methodology in medical imaging. PMID- 1631193 TI - Addendum to the code of practice for electron beam dosimetry in radiotherapy (1985): interim additional recommendations. Working Party of the IPSM. PMID- 1631194 TI - Registration of low resolution medical images. AB - There are several situations in which the registration of two medical images is desirable. One example is the registration of two images of the same organ taken using different radionuclide tracers, for example the ventilation and perfusion components of a V/Q lung scan, where the aim is to compare the regional uptake of the two tracers. Another example is the registration of images of an organ belonging to a single patient but taken at different times, where the aim is to follow changes in tracer uptake. Such techniques require a reliable method of registering images. One image is usually brought into registration with another image using a coordinate transfer function (CTF) and the central problem in image registration is the determination of the appropriate CTF. A new semi-automatic approach to the problem of finding the CTF for similar images is described which is especially applicable to low resolution images. PMID- 1631195 TI - Differences in the AC electrodynamics of viable and non-viable yeast cells determined through combined dielectrophoresis and electrorotation studies. AB - An electrode system is described for the near-simultaneous application and measurement of translational, levitational and rotational forces induced by AC electric fields, and this has been used to investigate the differences in the AC electrodynamics of viable and non-viable yeast cells. A new approach to the theoretical modelling of the experimental data has enabled these differences to be quantified in terms of changes in the conductivity of the cytoplasmic membrane and cell interior. The results are considered to have potentially important biomedical and biotechnological applications. PMID- 1631196 TI - Contrast agent CT imaging in variable sized organs using single energy synchrotron radiation. AB - A theoretical and experimental study has been performed to determine which element, when used as a contrast agent in CT, requires the lowest concentration when delivered to various sized organs. Iodine is at present the primary contrast agent used in contrast enhanced CT imaging. The results presented here show that iodine is not the optimum element to use in terms of concentration needed for visibility. When administered to very small organs, the use of gadolinium reduces the concentration required for visibility by at least a factor of 3 over that required when using iodine. PMID- 1631197 TI - The theoretical basis for the determination of optical pathlengths in tissue: temporal and frequency analysis. AB - A concise theoretical treatment is developed for the calculation of mean time, differential pathlength, phase shift, modulation depth and integrated intensity of measurements of light intensity as a function of time on the surface of tissue, resulting from either the input of picosecond light pulses, or radio frequency-modulated light. The treatment uses the Green's function of the diffusion approximation to the radiative transfer equation, and develops this and its Fourier transform in a variety of geometries. Detailed comparisons are made of several of these parameters in several geometries, and their relation to experimentally measured clinical data. The limitations of the use of phase measurements is discussed. PMID- 1631198 TI - Effects of gradient timing and spatial resolution on the NMR signal from flowing blood. PMID- 1631199 TI - Determination of serum iron and iron binding capacity by NMR. PMID- 1631200 TI - Should 60Co tissue-air ratios be re-evaluated? PMID- 1631201 TI - Living without student research projects. PMID- 1631203 TI - Biomechanical comparison of the energy-storing capabilities of SACH and Carbon Copy II prosthetic feet during the stance phase of gait in a person with below knee amputation. AB - In this study, the energy-storing capabilities of solid-ankle cushion heel (SACH) and Carbon Copy II prosthetic feet during the stance phase of gait were compared. A person with a unilateral below-knee amputation served as a component of the instrumentation to test the feet under dynamic loads. Ten trials per foot of bilateral stride at "free" velocity were collected with a video-based, three dimensional data-acquisition system and two force plates. There were no differences between the prosthetic conditions in step length, single-limb support time, and swing period (analysis of variance) or in double-limb support time, cadence, and velocity (Student's t test). Angular kinematics and moments of the hip and knee were unaffected bilaterally by the type of foot. The progression of the center of pressure under the Carbon Copy II was delayed from 15% to 80% of stance as compared with the SACH foot. The Carbon Copy II showed slower unloading in late stance and a later peak propulsive force than did the SACH foot. The Carbon Copy II performed greater work in both the energy-storage (Carbon Copy II = 2.33 J, SACH = 1.16 J) and energy-return (Carbon Copy II = 1.33 J, SACH = 0.34 J) phases of stance and returned energy with 57% efficiency. Although the energy returned by the Carbon Copy II was clinically insignificant during level walking, these results confirm that it performs as an energy-storing device. PMID- 1631202 TI - Investigation of evidence for anticipatory postural adjustments in seated subjects who performed a reaching task. AB - The paradigm for study of anticipatory postural adjustments permits investigation of the coordination of postural and voluntary components of functional movement. The purpose of this study was to investigate whether there were anticipatory postural adjustments for voluntary movement in seated subjects under clinically relevant conditions. Eight neurologically normal subjects performed a reaching task to a target placed at shoulder height, 45 degrees to the right of midline. Onsets and magnitudes of lateral and fore-aft reactive forces associated with the movement and of electromyographic (EMG) activity of the ipsilateral deltoid and external abdominal oblique and contralateral paraspinal muscles were monitored. Conditions of trunk support, reach speed, and distance reached were manipulated. Onsets of deltoid muscle EMG activity preceded onsets of postural muscle (external oblique and paraspinal) EMG activity in 70% of all trials for seated subjects in contrast to reports of EMG activity onset in the postural muscles in advance of the prime mover in standing subjects who performed a similar task. The role of the trunk musculature and the significance of reactive forces in advance of hand movement were equivocal. This study has implications for evaluation of postural instability in persons unable to stand for testing. PMID- 1631204 TI - Clinical management of a patient following temporomandibular joint arthroscopy. AB - This case report describes a patient in whom arthroscopic surgery of the temporomandibular joint (TMJ) was used to break up adhesions between the TMJ disc and the articular eminence and therefore improve mobility of the joint. Postsurgical physical therapy procedures used were high voltage electrical stimulation, transcutaneous electrical nerve stimulation, moist heat, ultrasound, ice, mobilization, and therapeutic exercises. Postsurgical goals included normalization of range of motion, elimination of pain, elimination of inflammation, and mandibular function without restriction. Special emphasis is given to an unusually effective mobilization technique used to decrease tenderness in the TMJ. The conservative therapy described may be used for persons with similar symptoms and evaluation findings who do not require surgery. [Waide FL, Bade DM, Lovasko J, Montana J. Clinical management of a patient following temporomandibular joint arthroscopy. PMID- 1631206 TI - Changes in hand function in the aging adult as determined by the Jebsen Test of Hand Function. AB - The Jebsen Test of Hand Function is used to assess a broad range of hand functions required for activities of daily living. The time needed to complete a variety of subtests is measured, with high scores indicative of abnormality. Normative values have been established for men and women in two age groups: 20 to 59 years and 60 to 94 years. The purpose of this study was to determine whether hand function, as measured by the Jebsen test, declines with age in subjects over the age of 60 years. A total of 121 men and women were given the test and grouped into the following age categories: (1) 60 to 69 years, (2) 70 to 79 years, and (3) 80 to 89 years. Hand function decreased with age in both men and women. There were significant positive correlations between age and time needed to complete the various subtests, and analyses of variance revealed significant differences between subjects in their 80s and those in their 60s and 70s. In only a few tasks were there significant differences between men and women within any age group. Because of the decrease in normal function with age, measurements obtained with the Jebsen test in the elderly should be compared with normative values that are obtained from similarly aged subjects. [Hackel ME, Wolfe GA, Bang SM, Canfield JS. Changes in hand function in the aging adult as determined by the Jebsen Test of Hand Function. PMID- 1631205 TI - Exercise response in children with and without juvenile rheumatoid arthritis: a case-comparison study. AB - The primary purpose of the study was to compare the response to bicycle ergometer exercise in children with and without juvenile rheumatoid arthritis (JRA). Heart rate, exercise duration, highest work load completed, and peak oxygen consumption (peak VO2) were compared. A secondary purpose of the study was to determine the relationship between peak VO2 and articular disease severity. Thirty children with JRA and 30 controls matched for age, sex, and body surface area (BSA) were the subjects. Peak VO2 was determined by an open-circuit computerized gas analysis system. Peak VO2, highest work load completed, exercise duration, and peak heart rate were significantly lower among the children with JRA than their respective controls. Submaximal heart rate was significantly higher for the children with JRA. There was no difference in resting heart rate between the two groups. There was no relationship between peak VO2 and articular disease severity among the children with JRA. The results suggest that aerobic conditioning programs may be indicated soon after diagnosis for patients with JRA, regardless of the severity of their articular disease. One subject with JRA and 2 control subjects reported light-headedness and dizziness, and 1 subject with JRA complained of increased knee swelling. We recommend that physical therapists monitor patients for signs of exercise intolerance and joint symptoms during exercise training sessions. [Jasso Giannini M, Protas EJ. Exercise response in children with and without juvenile rheumatoid arthritis: a case-comparison study. PMID- 1631207 TI - American Physical Therapy Association environmental statement. PMID- 1631208 TI - The Ilizarov method. PMID- 1631209 TI - Academics and clinical research. PMID- 1631210 TI - Fetal fracture healing in a lamb model. AB - A large animal model to assess fetal fracture repair and the ability to close excisional bony defects is presented. Incisional and excisional ulnar fractures were made in 14 midgestation fetal lambs, harvested at serial time points, and subjected to high-resolution low-kilovolt magnification radiographs, magnetic resonance imaging scans, and histologic analysis. Fetal fracture healing was characterized by early closure of excisional defects and rapid fracture healing with minimal or no soft-tissue inflammation or callus formation. Magnetic resonance imaging scans of the fractures revealed a characteristic pattern compatible with the histologic findings, namely, minimal inflammation in soft tissue adjacent to the fracture site. Histologic and magnification radiographic findings indicated that complete bony repair occurred within 21 days in incisional defects and within 40 days in excisional defects. In both cases, healed fetal bone resembled normal bone matrix. Excisional defects, including periosteum, of greater than three times the width of the bony cortex closed rapidly with virtually normal-appearing bony matrix and with minimal or no callus formation. PMID- 1631211 TI - Are growth alterations a consequence of surgery for prominent ears? AB - This study was undertaken to detect growth alterations after surgery for prominent ears. The cartilage excision technique was used in all 77 patients seen for follow-up. Two hundred students served as controls. Auricular measurements were done according to standardized guidelines of anthropometry. There was no significant difference between the retroauricular angle in the surgical group and in controls. The morphologic ear length in the surgical group was significantly smaller than in controls. Maximum ear length was significantly greater in men. Our measurements in the control group were significant below the reference values reported in the literature. Comparing the ear index of both groups with published data, we found a harmony between the width and the length of the ear. We could demonstrate that prominent ears were significantly larger in all other dimensions and that auricular growth does not stop following surgery for prominent ears with the cartilage excision method. We also evaluated subjective criteria such as tolerance to cold, scar formation, and patient satisfaction. PMID- 1631212 TI - The use of Gore-Tex implants in aesthetic surgery of the face. AB - Deep wrinkles and folds usually are not completely or permanently corrected with face lifting, fat or collagen injections, chemical peels, and other known procedures. It is suggested that a permanent implant, well tolerated by human tissues, could be helpful as an isolated or associated procedure. An expanded synthetic polymer known as Gore-Tex expanded polytetrafluoroethylene soft-tissue patch is available and is easy to use to approximate and correct defects; it also can be used as a filling material or to replace other kinds of prostheses to get better projection of frontal, orbital, malar, and chin areas. I have used this material in my clinic for 5 years. Indications and results of the first cosmetic cases are reported herein. PMID- 1631213 TI - The ptotic (witch's) chin deformity: an excisional approach. AB - Ptosis of the chin pad is common and can be seen in patients of all ages. It may be associated with too little or (at times) too much anterior chin projection. Often there is an associated deep submental skin crease present. Frequently, the primary concern of the patient is the appearance or exaggeration of chin ptosis in smiling ("dynamic" ptosis). This report describes a flexible approach to the correction of developmental (and some iatrogenic) ptotic chin deformities. The key element in the approach is the direct excision of sagging or excess chin fat, muscle, and skin. No attempt is made to reposition or lift ptosis-prone soft tissues. If a deep submental skin crease is present, it too is excised. If the chin needs added anterior projection, it is accomplished with a stable alloplastic chin implant. The approach is uniquely suited to correct anterior overprojection caused by an excess of soft tissue at the front of the chin and has been successful in correcting the "dynamic" ptosis that appears with smiling. PMID- 1631214 TI - Mandibular retrusion, temporomandibular joint derangement, and orthognathic surgery planning. AB - One-hundred consecutive orthognathic surgery candidates with mandibular retrusion were selected for retrospective analysis. Patients had undergone imaging studies that included magnetic resonance imaging (MRI) of both temporomandibular joints to assess the presence or absence, stage, and activity of suspected internal derangement(s). Patients were divided into stable and unstable deformity groups based on the presence or absence of change in their facial contour and/or occlusal disturbances in the 24 months prior to evaluation. Each of the 58 unstable and 30 of 42 stable patients were found to have internal derangements of at least one temporomandibular joint. The degree of joint degeneration directly paralleled the severity of retrognathia in most cases. We concluded that temporomandibular joint internal derangement is common in cases of mandibular retrusion and leads to the facial morphology in a high percentage of patients. Preoperative temporomandibular joint imaging with MRI is recommended prior to orthognathic surgical correction of retrognathic deformities. PMID- 1631215 TI - The L short-scar mammaplasty: a new approach. AB - An improved L mammaplasty technique was employed in 178 patients aged 13 to 55 years, with reductions of up to 1280 gm per breast, with small, well-positioned, and undistorted scars. I have obtained a satisfactory final shape of the breast with no major complications over a 3-year follow-up period. The markings are based on chest width and on the quantity of skin that will remain. The technique allows the surgeon to remove more skin, and it is indicated for minor, moderate, and large hypertrophies, as well as for ptotic and asymmetrical breasts. The resection comprises skin and mammary tissue from the inferior and middle portions of the breast, preserving the main lactiferous ducts. In case of hypertrophic breasts, the base is removed, preserving the branches of the lateral cutaneous nerves, which derive from the third, fourth, and fifth intercostal nerves. PMID- 1631216 TI - A clinical comparison of the tendency to capsular contracture between smooth and textured gel-filled silicone mammary implants. AB - The aim of this prospective, controlled clinical investigation was to find out if there is a difference in the capsular contracture rate between silicone implants with a smooth or textured surface as the only difference. Twenty-five women with bilateral mammary hypoplasia underwent mammary augmentation. All got a textured implant on one side and a smooth implant on the other. The implants were placed subglandularly. Follow-up examinations were done on six occasions. Three parameters were used for estimation of the tendency to capsular contracture: (1) the patient's opinion on differences in hardness of the breasts, (2) the investigator's classification of capsular contracture, and (3) applanation tonometry. At the end of the follow-up period, after 1 year, all parameters showed with no doubt that the breasts augmented with textured implants had a lower tendency to develop contracting capsules than the breasts augmented with smooth implants. PMID- 1631217 TI - Immediate breast reconstruction: why the free TRAM over the conventional TRAM flap? AB - Use of the transverse rectus abdominis myocutaneous (TRAM) flap for immediate breast reconstruction is controversial because of fear of flap loss and concern that a high complication rate could interfere with adjuvant therapy. One common complication of the TRAM, partial flap necrosis, can interfere with both institution of postoperative therapy and evaluation for recurrence. In an attempt to minimize this problem, we began using the free TRAM flap based on the inferior deep epigastric vessels. This study compares our experience with conventional superior-pedicled (cTRAM) flaps and free TRAM (fTRAM) flaps. A total of 68 breasts were reconstructed in 63 patients, of which 48 of 68 (71 percent) were conventional TRAM flaps and 20 of 68 (29 percent) were free TRAM flaps. Of the 48 conventional TRAM flaps, 26 (54 percent) were unipedicled and 22 (46 percent) were bipedicled. There were 39 of 48 (81 percent) conventional TRAM flaps and 17 of 20 (85 percent) free TRAM flaps with T1 or T2 lesions. Node-positive patients occurred in 14 of 48 (29 percent) conventional TRAM flaps and 2 of 20 (10 percent) free TRAM flaps. One-fourth of patients in both groups smoked cigarettes. Twenty-one of 48 patients (44 percent) with conventional TRAM flaps required postoperative chemotherapy, and 6 of 21 (29 percent) were delayed because of complications of the TRAM flap. Of the 7 of 20 (35 percent) free TRAM flap patients who required post-operative chemotherapy, only 1 of 7 (14 percent) was delayed because of TRAM flap complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1631218 TI - An anatomical basis for prognosis of malignant melanoma. AB - Clinical observations during surgery have led us to speculate that an anatomic basis may in fact exist for the poor prognosis associated with malignant melanoma arising in certain recognized "high-risk" areas. In our study we have treated and followed 45 patients with primary malignant melanoma for over 5 years. During the course of treatment, we identified variations in anatomic characteristics at the tumor sites. Criteria were established for high- and low-risk locations by the neurovascular structure encountered. We speculate that these sites that have neurovascular windows provide a readily accessible vascular pathway for the dissemination of malignant cells to deeper visceral structures and may account for the poor prognosis associated with primary lesions in these locations. Thirty patients were classified as being at high risk for developing metastasis, whereas 13 were classified as being at low risk; 2 patients were in a special-risk category. To date, 12 of the 30 patients with "high-risk" melanoma have gone on to develop metastatic disease, which represents 40 percent of that group, whereas none of the patients classified as "low risk" have developed metastases during the same period. PMID- 1631219 TI - The extended V-Y flap. AB - The extended V-Y flap is a modification of the V-Y advancement flap, which is very useful in closing defects following excision of facial lesions. The modification involves the addition of an extension limb onto the advancing edge of the standard flap. This limb is located adjacent to the area requiring reconstruction and is hinged down as a transposition flap on the end of the V-Y advancement flap to close the most distal portion of the defect. The extended V-Y flap has been found to be very effective in closing large defects in areas that typically have inadequate subcutaneous tissue to allow extensive mobilization of the standard V-Y advancement flap. It has been used effectively with excellent cosmetic results in the temporal, scalp, forehead, and nasal areas, providing a well-contoured and aesthetically pleasing reconstruction. PMID- 1631221 TI - Full-thickness skin wound explants in tissue culture: a mechanical evaluation of healing. AB - This study was designed to evaluate biomechanically defined wound healing in full thickness skin explants in tissue culture. The requirement for preculture incubation of wounds in situ was characterized. Full-thickness skin incisions were made in 44 rats and closed immediately. Wounds were incubated in situ for 0, 12, 24, 36, 48, 72, or 96 hours before harvesting and placement into tissue culture media for 6 weeks. Healing was evaluated by biomechanical criteria: tensiometric distraction to wound rupture generated true stress and energy absorption data. Burst-strength (maximum true stress) and toughness (energy absorption) were five times higher in the 48-hour group than in any other group; other groups were not different from each other. This study demonstrates long term survival of full-thickness skin in culture and shows that full-thickness skin explants heal in tissue culture. Possible explanations for the narrow window of opportunity for harvest (48 hours, no more and no less) are discussed. PMID- 1631220 TI - Prevention of microvascular thrombosis with low-dose tissue plasminogen activator. AB - In a blind, randomized study, two groups, each of seven rabbits, were treated with either a very low dose of human melanoma cell line-derived tissue-type plasminogen activator (t-PA) or isotonic saline. t-PA (0.067 mg/kg of body weight) was administered intraaortically, 20 percent being given as a 30-second "bolus" infusion just prior to the reperfusion of intimectomized central ear arteries and the rest as a continuous infusion during the next 2 hours. Arteriotomic bleeding times, accumulations of 32P-labeled platelets, patency, and sizes of thrombus deposits 2 hours after reperfusion were recorded. To confirm the presence of tissue plasminogen activator in plasma, fibrin-plate lysis assays of arterial plasma were performed immediately before and 1/2 hour and 2 hours after starting drug infusion. Arteriotomic bleeding times were similar in both groups. Transient "oozing" from wound edges occurred in 40 percent of rabbits treated with tissue plasminogen activator. Patency was significantly increased and thrombus deposits were smaller in the tissue plasminogen activator group. Plasma from animals treated with tissue plasminogen activator caused massive lysis of fibrin plates, whereas plasma from control animals caused little or no lysis. Platelet accumulations were very similar in both groups, indicating that occlusive thrombi mainly consisted of other elements than platelets (e.g., fibrin and red cells). Scanning electron microscopy showed normally adhering and aggregating platelets in both groups. This study shows that mild fibrinolytic stimulation with tissue plasminogen activator significantly improves patency in severely traumatized small-caliber arteries and indicates that such treatment may be one approach to prevent thrombosis at microvascular anastomotic sites. PMID- 1631222 TI - Where angels fear to tread. PMID- 1631223 TI - Juvenile breast hypertrophy: report of a familial pattern and review of the literature. AB - Juvenile hypertrophy of the breast is a relatively rare condition rapidly leading to gigantomastia in peripubertal females. The pathology is limited to the breast, with otherwise normal growth and development. We have reported the first familial pattern seen in this unusual condition. Ablation of the breast is always required. We favor reduction mammaplasty to avoid breast implants, despite the need for additional procedures secondary to recurrent hypertrophy. Our second patient provides support for this approach, demonstrating amelioration in breast growth despite the initial period of rapid regrowth. PMID- 1631224 TI - Acute repair of a full-thickness right ventricular defect with a composite myofascial pedicle flap. AB - A full-thickness defect of the right ventricle presented acutely after mediastinitis and sternal dehiscence. This developed 29 days after bilateral internal mammary artery harvest for coronary artery bypass grafting. The defect was managed successfully with a pedicled left rectus abdominis muscle flap using an attached island of the anterior rectus sheath for endocardial lining. The vascular anatomic basis for viability of the rectus abdominis muscle flap after internal mammary artery harvest is derived primarily from musculophrenic, lumbar, lower sixth intercostal, and subcostal artery communications. In addition, the advantages of a myofascial pedicle flap for reconstruction of full-thickness cardiac defects are its ready availability and a strong anterior fascial sheath that can be used as a neoendocardial lining. The patient did well and remains asymptomatic after 3 years. PMID- 1631225 TI - Augmentation of the failed pharyngeal flap. AB - Pharyngeal flaps are frequently used with good results to eliminate hypernasality and/or nasal escape. In a small percentage of patients, however, cicatricial contracture of the flap occurs to such a degree that velopharyngeal incompetence returns. The authors have devised a method of augmenting the scarred flap with small, superiorly based flaps lateral and adjacent to the original flap. Four cases are presented in which speech analysis was conducted prior to the procedure and then for 9 to 24 months postoperatively. The postoperative speech results are all within normal limits. PMID- 1631226 TI - Flap models in the rat: a review and reappraisal. AB - The laboratory rat has long provided plastic surgical investigators a model to study many aspects of flap physiology. Clinical advances in reconstructive surgery have succeeded or preceded experimental work, setting the stage for further advances. We have critically reviewed all reports of flap models in the laboratory rat. This has begun with simple skin flaps designed on various areas of the body and continued with a review of free-tissue transfer models. Because of the multitude of as yet unanswered questions remaining, the laboratory rat will invariably continue to be widely used as an investigatory source in this area. This report should allow investigators to select more easily reliable, reproducible experimental models, and, one hopes, to streamline their investigative efforts. PMID- 1631227 TI - Hirsutism. PMID- 1631228 TI - Plastic surgery and psychotherapy in the treatment of psychologically disturbed patients. PMID- 1631229 TI - Cutis aplasia. PMID- 1631230 TI - Human bites of the hand. PMID- 1631231 TI - Decompression of ophthalmopathy. PMID- 1631232 TI - Not augmenting the opposite breast after postmastectomy reconstruction. PMID- 1631233 TI - The use of bacitracin ointment to avoid shaving the scalp for rhytidectomy. PMID- 1631234 TI - Could tight breast capsules "squeeze" a significant amount of silicone gel out of an implant? PMID- 1631235 TI - The fan principle in skin flaps. PMID- 1631236 TI - Posterior auricular keloids as a complication of conchal cartilage grafts in blacks. PMID- 1631237 TI - Intraoral versus intranasal approach to lateral osteotomy. PMID- 1631238 TI - Breast implants, the FDA, and trial lawyers. PMID- 1631240 TI - Breast implants and life's dangers. PMID- 1631239 TI - Suprapubic "intracath" cystostomy. PMID- 1631241 TI - The conventional and low-bleed implants for augmentation mammaplasty. PMID- 1631242 TI - Endonuclease A degrades chromosomal and plasmid DNA of Escherichia coli present in most preparations of single stranded DNA from phagemids. AB - With E. coli, large and variable amounts of chromosomal and plasmid DNAs are observed in the supernatants of overnight cultures when the cells carry an endA mutation, but are not detected by gel electrophoresis when the cells carry the wild type allele of endA. Significant amounts of nuclease activity in DH11S endA+ supernatants were detected by two simple assays; the rapid degradation of added pBR322 plasmid DNA, as judged by agarose gel electrophoresis, and a decrease of more than 100000 fold in transformation efficiency of the added pBR322 plasmid DNA. By employing isogenic endA mutant and wild type strains of DH11S and DH10B/F' proAB+ laclq Z delta M15, it was shown that detectable levels of chromosomal and plasmid DNAs are observed only in the endA mutant strains. These results indicate that Endonuclease I activity is responsible for degradation of chromosomal and plasmid DNA usually present in preparations of ssDNA. Therefore, a wild type endA gene is useful for the rapid and simple production of highly purified ssDNA from cells containing phagemid vectors. PMID- 1631243 TI - Removal of copper ion by Pseudomonas spp. AB - Copper-resistant Pseudomonas sp. 41Y, Pseudomonas pseudomallei 13-1 and Pseudomonas aeruginosa 7 were used in the present study. When the latter two organisms were added to copper-containing 1/3 strength Tryptic Soy Broth, more than 99.5% of the copper ion was removed from the medium within 24 h. If copper solution was added to hog waste slurry, a reduction in the copper ion concentration could be detected only when the added bacteria started to grow in it, whereas in a mineral medium supplemented with glycerol-2-phosphate, both bacteria could remove about 50% of the copper ion from the medium within 24 h. When cell suspension of Pseudomonas sp. 41Y was autoclaved, no copper ion removal was observed. Different incubation temperatures, including 30 degrees C, 37 degrees C and 45 degrees C, had no effect on the percent of copper ion removed by both Pseudomonas sp. 41Y and P. pseudomallei 13-1. On the other hand, if the pH value of the solution was lowered from 8.2 to 6.0, there was a drastic decrease in copper removal. A similar reduction of copper ion removal ability was also observed with the addition of lead ion. When cells of Pseudomonas sp. 41Y were embedded in sodium alginate, there was a decrease in its ability to remove copper ion as compared to the free-living cells. PMID- 1631244 TI - Fate of the autologous tri-cusp-valved pericardial conduit in the right ventricular outflow tract of growing pigs. AB - No perfect valve or valved conduit is currently available to reconstruct the right ventricular outflow tract (RVOT) in pediatric patients. To investigate the fate of autologous pericardial valved conduit, twenty piglets weighing 12.2 +/- 1.4 kg were divided into two groups. In 10 of them, the pericardium was immersed in 0.6% glutaraldehyde for 5 minutes (Gr PG) and then washed with normal saline. In the other 10 pigs, the pericardium was immersed in normal saline only (Gr PN) after procurement. Afterwards the autologous pericardium was tailored as designed to build a tri-cusp-valve inside the pericardial conduit with reconstruction of the sinus of Valsalva. This conduit was connected to the pulmonary trunk (PT) distally and RVOT proximally without a pump. The PT was then doubly ligated just above the annulus. The pigs survived 114 +/- 92 days in Gr PG and 82 +/- 50 days in Gr PN. The body weight increased to 42 +/- 29 kg in Gr PG and 30 +/- 9 kg in Gr PN. No cusps adhered to the conduit wall in either group. In Gr PN, the valve became retracted; in 7 of them an aneurysm developed proximal to the stenotic pulmonary valve, while only one pig in Gr PG developed an aneurysm. In Gr PG, the leaflet and conduit showed evidence of growth. In contrast, no evidence of valve growth was found in Gr PN. Calcification was evident more in Gr PG than in Gr PN either on the leaflet (9/10 vs. 5/10) or in the wall of conduit (8/10 vs. 6/10), but the differences were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1631245 TI - Effect of infection on nutritional status. AB - All infections no matter how mild decrease nutrient intakes and increase nutrient losses even when subclinical. The losses include decreased intestinal absorption, direct loss of nutrients in the gut, internal diversion for metabolic responses to infection and increased BMR when fever is present. Infection influences in this way not only protein and energy status but also that of most other nutrients. The clinical importance of these consequences of infection depends on the prior state of the individual, the nature and duration of the infection and the diet of the individual during the infection, particularly dietary intake during the convalescent period and whether full recovery takes place before another infection occurs. In industrialized countries particular attention must be paid to the nutrition of hospitalized patients since they are frequently debilitated by their primary disease, morbidity, and their nutritional status. Morbidity and mortality are increased by nosocomial infections to which the poorly nourished individual is more susceptible. PMID- 1631246 TI - A new codon 31 (-C) mutant resulting in beta zero-thalassemia. AB - A new beta zero-thalassemia mutation, a frameshift mutation with deletion of a single cytosine nucleotide in codon 31, is described. The propositus, which is compound heterozygous for this mutation and the 17 beta A-T beta zero-thalassemia mutation, has the phenotype of severe beta-thalassemia major. PMID- 1631247 TI - Deterioration on the Blessed test in Alzheimer's disease: longitudinal data and their implications for clinical trials and identification of subtypes. AB - One hundred eleven patients with probable Alzheimer's disease (AD) were given the Blessed test (BT) of information, memory, and concentration (scored 0-33) at 6 month intervals over periods of 6-96 months. For each patient, the change in the total BT score between pairs of visits at 6- and 12-month intervals was measured. Mean deterioration scores over 6 and 12 months were 2.2 (SD = 3.2) and 4.1 (SD = 4.1) points, respectively. There was no significant correlation between degree of dementia on the BT and the rate of deterioration. Gender, age of onset, and family history had no significant effect on the rate of deterioration. The implications of the results for treatment trials and investigations of clinical heterogeneity are discussed. PMID- 1631248 TI - Psychiatric disorders in the families of patients with obsessive-compulsive disorder. AB - The rate of comorbid diagnoses in a group of 92 patients with obsessive compulsive disorder (OCD) was examined, with particular attention being paid to mood disorders. The family history method was used to study the frequency of psychiatric disorders in the patients' families and to analyze the characteristics of the familial loading for OCD and mood disorders. A comorbid diagnosis of mood disorder occurred in 35.9% of the patients. The morbidity risk for OCD in the patients' families accounted for 3.4%; when 21 patients with an age of onset under 14 were examined, the morbidity risk in first degree relatives reached 8.8%. This tendency did not appear to be true for mood disorders. PMID- 1631249 TI - Neopterin production in acute schizophrenic patients: an indicator of alterations of cell-mediated immunity. AB - This longitudinal study analyzed how the activation of cell-mediated immunity (CMI) was related to the severity of symptomatology in 25 acute schizophrenic inpatients (DSM-III-R, 295.31). Neopterin, which was used to monitor the activation of T-cells and macrophages, was found to be within the normal range, but the lowest neopterin concentrations were measured on day 0. By day 3, a significant increase of neopterin was observed. Compared with healthy controls, patients had significantly lower neopterin levels at baseline. The highest scores on the Clinical Global Impressions Scale and the Brief Psychiatric Rating Scale occurred on day 0 and decreased significantly over the observation period. In general, the increase of neopterin was accompanied by a decrease in psychopathological symptoms. These results' indicate that at study entry, when patients are acutely ill, activation of the CMI is reduced rather than increased. Possible pathophysiological mechanisms are discussed. PMID- 1631250 TI - Level of haloperidol in plasma is related to electroencephalographic findings in patients who improve. AB - This study analyzed interrelationships among plasma level of haloperidol (HAL), electroencephalographic (EEG) changes, and clinical response in 37 acutely exacerbated schizophrenic patients after a 6-week period of treatment. Two hypotheses were tested: (1) EEG theta response to HAL depends on levels of HAL in plasma, and this relationship is expressed in patients showing a clear clinical response (responders). (2) Responders and nonresponders are characterized by a different neuroleptic EEG profile. EEG examinations (resting, waking EEG) were performed at study entry, end point of the placebo period ("baseline"), and weekly during the entire HAL treatment period. EEG response was measured by power spectral changes in four frequency bands (delta, theta, alpha, and beta); clinical response was assessed by the Brief Psychiatric Rating Scale. There was a significant relationship between HAL plasma levels and EEG theta activity for treatment responders, whereas no relationship was detected for the nonresponders. Furthermore, there were EEG changes (in the delta and alpha bands) that depended on clinical response but did not show any relationship, either in responders or nonresponders, to HAL plasma levels. These results supported both hypotheses. PMID- 1631251 TI - Prolactin responses to domperidone in chronic schizophrenia. AB - The prolactin response to 20 mg of domperidone, a peripheral dopamine receptor antagonist, was evaluated in a group of 17 male, drug-free, elderly, chronic schizophrenic patients and 8 age-matched male normal control subjects. Both groups of subjects were receiving a variety of nonpsychotropic medications not known to affect the prolactin response to dopamine receptor antagonists. Basal plasma prolactin levels did not differ between the two groups. However, the prolactin response following domperidone was significantly greater in the schizophrenic patients, although plasma domperidone levels did not differ between the two groups. This effect is opposite to the previously reported effect of domperidone in young schizophrenic patients compared with age-matched control subjects (Nerozzi et al., 1990). The prolactin response to domperidone was markedly smaller in the old compared with the young normal control subjects, whereas the young and old schizophrenic patients had identical responses. Possible explanations for these results are considered, especially the possibility of abnormalities in the release of dopamine and pituitary D2 dopamine receptors in the elderly schizophrenic patients compared with age-matched normal control subjects. PMID- 1631252 TI - Patterns of comorbidity in panic disorder and agoraphobia. AB - Diagnoses of comorbid disorders were determined in a sample of 54 patients with panic disorder as defined in DSM-III-R. The sample was divided into the following three groups: (1) uncomplicated panic disorder (PDU); (2) panic disorder with mild agoraphobia (PDM); and (3) panic disorder with moderate to severe agoraphobia (PDA). In comparison with patients with PDU, patients with PDA had higher comorbidity rates in general, received multiple comorbid diagnoses more frequently, had a higher prevalence of major depression, dysthymia, social phobia, generalized anxiety disorder, and obsessive-compulsive disorder, and scored higher on most measures of self-rated psychopathology. These findings support the notion that PDA may be a disorder essentially different from PDU. PMID- 1631254 TI - Case of neurological and behavioral abnormalities: due to Borna disease virus encephalitis? PMID- 1631253 TI - Effects of fenfluramine on plasma HVA in OCD. PMID- 1631255 TI - Should we add corticosteroids to the treatment of acute bacterial meningitis? PMID- 1631256 TI - Primary biliary cirrhosis--from Thomas Addison to the 1990s. PMID- 1631257 TI - Therapeutic potential of botulinum toxin in neurological disorders. PMID- 1631258 TI - Clonidine therapy for Shapiro's syndrome. AB - Shapiro's syndrome comprises agenesis of the corpus callosum in association with episodic hyperhidrosis and hypothermia. We describe a 25-year-old man who is the twentieth case to be reported. There was no evidence of epilepsy, sympathetic nervous system dysfunction or inappropriate vasopressin release. However, investigation demonstrated a central defect in temperature regulation with an abnormally low hypothalamic set-point and normal homeothermic reflexes. Therapy with clonidine, an alpha 2-adrenoceptor agonist, was associated with remission of symptoms: these recurred on four occasions when clonidine was withdrawn. Clonidine therapy was also associated with a return to normal central temperature regulation. We suggest that the efficacy of clonidine reflects an action on hypothalamic thermoregulation rather than on peripheral catecholamine release. These findings have implications for the use of clonidine in other patients with Shapiro's syndrome and in more common disorders of temperature control, including perimenopausal flushing. PMID- 1631259 TI - Metabolic studies in kidney stone disease. AB - Patients with kidney stones (n = 59) and healthy controls (n = 31) collected a 24 hour urine sample and later underwent a 6-hour 'fast and load' test in which an oral calcium load was taken after 2 hours. In the 24-hour urine sample, mean calcium excretion was higher in patients than controls, while mean urate, oxalate and citrate levels were similar. The patients had higher levels of fasting plasma calcium, serum calcitriol and fasting urinary calcium, and lower levels of plasma phosphate than did the controls. Following the calcium load, plasma and urinary calcium increased similarly in both groups. Serum parathyroid hormone (PTH) levels were similar in both groups and decreased similarly following the calcium load. Multiple linear regression, relating the presence or absence of stone formation to all variables, found the only variables significantly related to stone formation to be plasma levels of calcium (p less than 0.001) and phosphate (p = 0.001) and fasting urinary urea (p less than 0.001), and 24-hour urinary calcium excretion (p less than 0.05). Urinary oxalate and citrate were not related to stone formation. The data do not support the hypothesis that primary stimulation by calcitriol produces a normal fasting plasma calcium level, with an exaggerated increase after an oral calcium load. The findings instead suggest an abnormality of parathyroid cell 'set point', such that PTH secretion continues until the plasma calcium level is a little higher and the phosphate a little lower than in controls. PMID- 1631260 TI - A quest for the relief of atherosclerosis: potential role of intrapulmonary heparin--a hypothesis. AB - Recent progress in the treatment of coronary artery disease is reviewed from the standpoint of changes in lifestyle, surgical techniques to revascularize the myocardium and a variety of medical interventions. Among the medical modalities, heparin appears to have a greater potential than any other agent tested to neutralize the atherogenic process at most of its stages. This potential is supported by success in clinical trials of heparin administered by intravenous, subcutaneous, pulmonary, sublingual and topical routes. The suggested self administration of low-dose heparin by inhalation appears to be well justified and easily adaptable to home therapy. The summarized evidence suggests the need for further clinical trials to test the use of heparin in the prophylaxis of atherosclerotic disease. PMID- 1631261 TI - Assessment of gall bladder dynamics, cholecystokinin release and the development of gallstones during octreotide therapy for acromegaly. AB - The development of gallstones is a well recognized complication of therapy with the long-acting somatostatin analogue, octreotide in patients with acromegaly. A group of nine acromegalic patients was treated with octreotide at doses of 300 600 micrograms daily for 8 months and the changes in fasting and post-prandial cholecystokinin release, and gall bladder motor function (determined by a radiosotopic technique) were assessed at regular intervals. In addition the development of any gallstones was determined by serial ultrasonography. Fasting cholecystokinin levels showed no significant change over 6 months, whereas the post-prandial levels demonstrated a significant decrease (p less than 0.01) during therapy, yet remained significantly higher than fasting levels. Twenty four hours after commencing therapy gall bladder ejection fraction was decreased by 57 +/- 23 per cent and gall bladder ejection rate decreased by 63 +/- 19 per cent compared to the pretreatment values, whereas after 6 months' therapy a marked reduction in gall bladder ejection fraction (greater than 35 per cent) and gall bladder ejection rate (greater than 40 per cent) persisted in only four of nine patients. Three of these four patients with persistently impaired gall bladder motor function were subsequently shown to have developed either gallstones or biliary sludge during the course of therapy. We conclude that treatment with octreotide is associated with an impaired post-prandial release of cholecystokinin in all acromegalic patients, but gallstones only develop in those patients who, in addition, have evidence of a persistently impaired gall bladder motor response to cholecystokinin. PMID- 1631262 TI - Delirium in newly admitted elderly patients: a prospective study. AB - The prevalence, associated conditions and outcome of delirium were studied in a consecutive series of 184 patients admitted with acute illness to a department of health care of the elderly. Forty of these elderly subjects (22 per cent) met Diagnostic and Statistical Manual version 3 (revised) criteria for delirium. Screening for delirious patients using the abbreviated mental test on admission gave a high sensitivity (92 per cent). The conditions most commonly associated with delirium were infection and stroke. Onset of acute illness of less than 15 days, a reported history of dementia or recent confusion, and presence of a definite site of infection were much more likely in those with delirium. Serial use of the abbreviated mental test was a sensitive means of distinguishing delirious from other patients and may be useful in both the clinical and research setting. Delirious patients had more serious pre-existing disease than non delirious patients. They had a higher number of admissions during the 2 years prior to the index admission, a higher mortality rate and a higher rate of transfer to long-stay care than other patients, but no difference in duration of admission. All acutely ill elderly people should undergo an abbreviated mental test on admission, and if abnormal, this should be repeated as it will aid detection of delirium. PMID- 1631264 TI - The morbidity of multiple sclerosis. AB - Although the clinical course of multiple sclerosis is benign in up to one-third of patients, it is important to recognize the high rate of morbidity in others. Most individuals pass through a remitting phase but in a significant proportion the clinical manifestations subsequently recur, persist or slowly progress, and disability accumulates with time. Here we describe the frequency and spectrum of morbidity in a population based cohort of patients with multiple sclerosis. These statistics will guide those providing health care resources and planning services for patients with multiple sclerosis. PMID- 1631265 TI - Iatrogenic exfoliation of a tooth following abuse of a rubber dam: a case report. AB - This report presents a case in which tooth exfoliation followed rubber dam abuse. A 40-year-old patient was referred to the prosthodontic clinic with complaints of mobility and discomfort in tooth 44, which had received an amalgam restoration. While this tooth was scaled, a piece of rubber dam appeared in the buccal sulcus. Removal of the rubber piece was followed by thorough scaling and tooth splinting. Tooth deterioration continued, and concern for the adjacent teeth necessitated extraction of tooth 44. To avoid such undesirable consequences, the integrity of the dam should be verified on its removal. PMID- 1631263 TI - Lupus nephritis and pregnancy. AB - Sixty-four pregnancies in 41 women with biopsy proven lupus nephritis between 1965 and 1991 were analysed to record fetal and maternal outcome and identify risk factors for poor outcome. Of 65 fetuses, 22 (34 per cent) were lost (including therapeutic abortions), 19 (30 per cent) were live born but premature (less than or equal to 36 weeks gestation) and 24 (37 per cent) were term. Fetal loss after 20 weeks gestation was 19 per cent. Twelve per cent of 25 fetuses whose birthweight was recorded were small for gestational age. Maternal renal function deteriorated in 19 per cent of pregnancies but was irreversible post partum in only one woman (2 per cent). Hypertension was recorded in 44 per cent of pregnancies, developed early (less than or equal to 32 weeks gestation) in 28 per cent and was severe in 13 per cent. Treated hypertension predated 17 per cent of pregnancies and in 6 per cent (included in the overall incidence of hypertension) exacerbation occurred during pregnancy despite continued anti hypertensive medication. Nine women (22 per cent) who developed de novo hypertension in pregnancy had permanent hypertension post-partum. Increased proteinuria was recorded in 48 per cent of pregnancies and was irreversible post partum in 5 per cent. Comparison of pregnancies occurring before or after diagnosis was made by renal biopsy failed to show any significant difference in fetal outcome. Pregnancies occurring after the diagnosis of glomerulonephritis were associated with a significantly lower incidence of maternal hypertension, early hypertension, severe hypertension and increased proteinuria. The presence of the circulating lupus anticoagulant was clearly associated with a significantly high fetal loss rate although the incidence of maternal complications did not differ significantly between mothers positive or negative for lupus anticoagulant. PMID- 1631266 TI - Cardiovascular effects of local anesthesia with epinephrine in periodontal treatment. AB - To assess if the association of epinephrine with local anesthesia involves cardiovascular risks, 14 patients undergoing periodontal treatment were observed. Systolic and diastolic blood pressures and mean and maximal heart rates were analyzed. The comparison of basal and postanesthetic periods revealed a trend (nonsignificant) toward an increase in systolic blood pressure and a small, statistically significant increase in diastolic blood pressure; the heart rate increased in only a few patients, and never by more than 10 beats/min. The whole group showed a statistically significant reduction in mean and maximal heart rates from the basal period to an end-session period. Thus, in these patients, the given epinephrine doses resulted in negligible changes in heart rate and blood pressure. The reduction in heart rates at the end of treatment underlines the important role of the autonomic nervous system in the modulation of the cardiovascular response during dental sessions. PMID- 1631267 TI - Slip-casting alumina ceramics for crown and bridge restorations. AB - The In-Ceram technique uses alumina ceramics and glass in a two-step firing procedure to create a high-strength core material for single-tooth restorations as well as small fixed partial dentures. Fine-grain alumina particles are sintered to form a porous substructure, which is infiltrated with molten glass. The combination of these two processes gives the material its outstanding properties. The sintering process is almost without shrinkage, providing an excellent fit, while the glass infiltration leaves practically no porosities, resulting in high strength. PMID- 1631268 TI - Intentional replantation of a removable partial denture abutment tooth: a case report. AB - Intentional tooth replantation is a last-resort procedure, recommended only when all other techniques, short of tooth extraction, have been exhausted or are impractical. Although most endodontic textbooks describe the procedure, and many reports of intentional replantation have appeared in the dental literature, none have reported use of the technique to retain a removable partial denture abutment tooth. This article presents such a case and the rationale for the decision to intentionally replant. Eighteen-month follow-up clinical and radiographic results are presented. PMID- 1631269 TI - Resin bonding to wet substrate. 1. Bonding to dentin. AB - An in vitro study was undertaken to evaluate the ability of a dentin-enamel bonding system to bond to wet, as well as to dry, dentinal substrate. The All Etch/All-Bond system was used to bond to wet and dry dentin using 10% and 37% phosphoric acid surface conditioning. The wet dentinal surfaces exhibited significantly higher bond strengths than did the dry surfaces. It is suggested that, because of the unique behavior of the resin-primer mixture, the dentinal surface is adapted to much more thoroughly and intimately when the surface is wet. PMID- 1631270 TI - The dentinal surface: its influence on dentinal adhesion. 2. AB - The first paper in this series presented a categorization of dentinal adhesive systems that was organized roughly according to chronology, chemistry, and shear bond strength values. Category I dentinal adhesives demonstrate the lowest shear bond strength values, approximately 5 to 7 MPa. Category II dentinal adhesives, including experimental ferric and aluminum oxalate pretreatments and two commercial products, demonstrate shear bond strength values between 8 and 14 MPa. This second category of dentinal adhesives is the subject of this paper. An attempt is made to draw a parallel between the penetrative ability of the adhesive (the wettability of the dentinal substrate) and the efficacy of the adhesive bond as determined by shear bond strength values. Category III dentinal adhesives will be discussed in another paper. PMID- 1631271 TI - Use of self-curing composite resins to facilitate amalgam repair. AB - Resin cements, which have been shown to adhere to various metal alloys, were investigated as possible repair adhesives for dental amalgam. Test bars of repaired amalgam, formed by condensing new alloy against previously set alloy with or without the use of "adhesive" resins, were subjected to three-point bending measurements of transverse fracture strength. The results indicated that application of adhesive resin did not improve the breaking strength of the repaired specimens from that of specimens prepared without the use of such resins. The breaking strength of all repaired specimens was approximately 15% of the transverse fracture strength of the original intact amalgam bars. Scanning electron microscopy revealed that there was an intermixing of fresh amalgam and unset interfacial resin, which led to mechanical bonding of these materials, but there was no evidence of adhesion of the resin to the previously set amalgam. PMID- 1631272 TI - Surface topography of demineralized dentin preceded by formalin fixation. AB - Formalin treatment of dentin, prior to burnishing demineralization, results in a "tufted" collagen surface that may optimize bonding of hydroxyethyl methacrylate dentinal bonding agents. The purpose of this study was to determine if there is a clinically acceptable formalin treatment time that will yield a deeply tufted collagen surface. The exposed dentin of periodontally healthy and periodontally diseased human teeth was treated with formalin for various treatment times before "burnishing" demineralization with citric acid. Photographs of the specimens revealed that there was a statistically significant difference in the number of tufted surfaces found in the healthy group, as a whole, and the number found in the diseased group. No statistically significant difference was found among fixation times within either tooth group. It was concluded that 2 minutes of fixation was sufficient to produce a tufted fibrillar surface. PMID- 1631273 TI - Shear bond strengths of prosthodontic adhesive systems to a nickel-chromium beryllium alloy. AB - Panavia, a composite resin luting agent containing phosphate monomers, bonds chemically to air-abraded base metal alloys and is particularly suited for cementing resin-bonded retainers. Another adhesive methodology (Silicoater system) incorporates a pyrolytically applied silica layer to metal substrates to promote bonding of a resin adhesive. The object of this study was to compare prosthodontic adhesive systems that incorporated the Silicoater system and/or Panavia. The results showed that the surface treatment that provided significantly higher shear bond strengths was the Silicoater system and a layer of unfilled resin. A second test evaluated use of Panavia as a metal opaquing material beneath laboratory light-curing resins. Results showed that Panavia Opaque material was displaced peripherally during placement of overlying laboratory composite resin veneers. This resulted in an uneven intermediate layer of Panavia. PMID- 1631274 TI - The combined composite resin and amalgam restoration for posterior teeth: a clinical report. AB - This paper presents a technique for restoring maxillary posterior teeth with a combined composite resin and amalgam restoration when the preparation extends buccally into an esthetically critical area. This technique has two major advantages over traditional combined restorations: it requires only one clinical appointment, and it provides an esthetically acceptable result while maintaining the advantages of an amalgam restoration. A clinical assessment of 12 of these restorations, in vivo for 0.8 to 6.4 years, is presented. All but one restoration received a score of excellent or acceptable. PMID- 1631276 TI - The female pelvis. PMID- 1631275 TI - Transvaginal sonography of normal pelvic anatomy. AB - The major structures of interest in the pelvis for sonography are the uterus and ovaries. TVS, with its superior imaging characteristics, provides better sonographic detail of this anatomy and improves our diagnostic capabilities. It is certainly reasonable to expect this approach to yield even greater improvements in the future as the refinements to the technology continue to evolve. PMID- 1631277 TI - Transvaginal sonography of adnexal masses. AB - In conclusion, the clinical utility of TVS has expanded since its inception so that numerous gynecologic applications now exist. TVS has most certainly had a major impact upon the diagnosis of adnexal disease. The addition of duplex and color Doppler capability to vaginal probes has expanded further the scope of TVS. In our laboratory, TVS is used as an adjunctive tool to complement TAS in cases of inadequate bladder distention, incomplete evaluation of the pelvis, and equivocal findings that require improved visualization for diagnosis. TVS is now recognized as the procedure of choice in the evaluation of patients who have a suspected ectopic pregnancy. It also can be used as the initial procedure in the follow-up of a known adnexal process. This article has emphasized how TVS can contribute to the diagnosis of cystic, complex, and solid adnexal masses. With continued technologic advancements, additional applications for TVS are likely to emerge. PMID- 1631278 TI - Conventional and color Doppler transvaginal sonography in gynecologic infertility. Current clinical applications. AB - TVS affords accurate follicular monitoring and guidance for follicular aspiration. The role of TVS in assessing the adequacy of the endometrium is still undergoing investigation. Our studies suggest that there is a statistically significant difference in the pregnancy rate when the endometrium has a multilayered appearance. Infertility patients who successfully achieve pregnancy should be monitored with TVS because of a higher incidence of ectopic pregnancy, anembryonic gestation, and spontaneous abortion. TVS has a secondary role in evaluating certain uterine malformations and tubal disorders. With TV-CDS it is also possible to evaluate physiologic parameters such as adnexal and uterine blood flow. The role of TV-CDS in the anatomic and physiologic evaluation of early pregnancy is now being established. PMID- 1631279 TI - Transvaginal ultrasonography of pelvic neoplasms. AB - The recent development of the high resolution transvaginal probe has increased the diagnostic sensitivity and specificity of transabdominal sonography. This article reviews the applications of transvaginal sonography with pulsed and color flow Doppler imaging to the diagnosis and management of uterine, ovarian, and metastatic pelvic neoplasms. PMID- 1631280 TI - Doppler ultrasonography of the pelvis. AB - TVS has brought the pelvic organs closer to us than ever before. Color Doppler probes have exposed small vessels that could not be seen with real-time technique alone, and pulsed Doppler is becoming an important adjunct in many physiologic and pathologic states. Vascular changes of the ovary and uterus during the menstrual cycle are now being followed during infertility protocols, are being investigated to determine the viability of an early pregnancy, and may increase our confidence in the diagnosis of an ectopic pregnancy in a few selected cases. Waveform analysis may be useful in discriminating benign from malignant uterine masses, and additional work in the diagnosis of pelvic thrombophlebitis and ovarian torsion is anticipated. Color Doppler sonography has an important role to play in the diagnosis of early ovarian cancer. A large multicenter trial is ongoing in this country to determine if there is a characteristic PI that will determine whether an adnexal mass is benign. While much of this work is preliminary, TV-CDS has tremendous potential in the assessment of pelvic disease. PMID- 1631282 TI - Transvaginal ultrasonography in postmenopausal patients. AB - Clearly, TVS has become an important adjunctive procedure in the evaluation of suspected gynecologic disease in postmenopausal women. In our laboratory, the additive value of TVS is approximately 50% in this population. A preliminary diagnosis on TAS may be completely altered--an abnormal finding better characterized or an equivocal lesion confirmed with certainty. Further investigative studies are required to establish firmly the indications for TVS in postmenopausal women. PMID- 1631281 TI - Ultrasonography of the female pelvis in childhood and adolescence. AB - The age of the patient is crucial in the consideration of differential diagnoses for pelvic disease. This is especially true in the pediatric population. Ultrasonography is the first, and often only, imaging required for female babies, children, and young adults who present with signs and symptoms referable to the pelvis. Usually, children come to attention because of pelvic mass, pelvic pain, ambiguous genitalia, or abnormal sexual development. It should be remembered that congenital anomalies may not become apparent until the onset of puberty. In all cases, good practice requires that adnexal and uterine anatomy and screening views of each kidney are documented on hard copy. Further evaluation, which consists of MR or CT scanning, depends on the results of the ultrasonograms, the clinical examination, and acuity of the problem. PMID- 1631283 TI - Magnetic resonance imaging of the normal female pelvis. AB - MR imaging has emerged as an important modality in the evaluation of the female pelvis as a result of the detailed demonstration of normal anatomy. Tissue planes within the uterus, cervix, vagina, and ovaries are clearly delineated, thus enabling a better understanding of normal anatomy and, therefore, pathology. PMID- 1631284 TI - Benign disease of the uterus and ovaries. Applications of magnetic resonance imaging. AB - Because of its relatively low cost, widespread availability, and patient tolerance ultrasound remains the primary modality for imaging the female pelvis. Nevertheless, MR imaging can contribute to cost-effective management in women who have suspected myomas or adenomyosis by establishing the diagnosis noninvasively. It can also improve management and reduce costs by providing precise presurgical mapping prior to myomectomy or correction of mullerian duct anomalies. In these instances, other tests such as hysterosalpingography and laparoscopy may be obviated if fallopian tube disease is not strongly suspected. MR imaging is also valuable in patients in whom suspected adnexal masses are not detected sonographically or in whom definitive diagnosis of juxta-uterine myoma, cystic teratoma, or hemorrhagic mass may alter management. PMID- 1631285 TI - Evaluation of gynecologic malignancy by magnetic resonance imaging. AB - Currently, MR imaging has demonstrated the greatest accuracy and has potentially the greatest clinical utility for the staging of cervical carcinoma. Endometrial carcinoma also can be staged by MR imaging with reasonable accuracy, although the clinical indications for preoperative endometrial carcinoma staging are less clear. MR imaging has unparalleled capacity for the tissue characterization of adnexal disease and has demonstrated utility for diagnosis of common adnexal masses such as pedunculated leiomyoma, endometrioma, and ovarian dermoid. Its use in the evaluation or staging of ovarian, vaginal, and vulvar carcinoma has not been evaluated fully. MR imaging can demonstrate complications of radiation therapy and surgery and can distinguish most recurrent carcinomas from postradiation fibrosis. New techniques such as arrayed use of surface coils, endoluminal surface coils, fast spin-echo acquisitions, and contrast agents show promise for contributing to the already rapid pace of technologic advancement in the field of MR imaging of the female pelvis. PMID- 1631286 TI - Magnetic resonance imaging of the pediatric pelvis. AB - The increased use of MR imaging in the pediatric population is due to the lack of ionizing radiation, multiplanar imaging capability, and excellent tissue contrast differentiation. MR imaging is most commonly indicated in the evaluation of tumors to provide information about resectability and extent of lesions. It is also useful in the evaluation of congenital anomalies of the pelvic organs. This is a rapidly changing field; the development of fast-scanning techniques and contrast agents for the bowel should further improve the utilization of MR imaging in pediatrics. PMID- 1631287 TI - Computed tomography of gynecologic neoplasms. AB - Both CT and MR imaging have had a major impact on gynecologic oncologic imaging, and new technology and imaging techniques are still being introduced. CT maintains a role in gynecologic pelvic cancer imaging because of cost effectiveness, high spatial resolution, fast examination time, and wide availability. CT is particularly advantageous for lymph node metastasis screening and guided-biopsy of metastases and recurrent tumor. CT currently is recommended for primary staging of ovarian cancer and advanced cancers of the cervix and endometrium, detection of persistent and metastatic gestational trophoblastic disease, and evaluation of recurrent gynecologic pelvic cancers. PMID- 1631288 TI - Computed tomographic evaluation of benign and inflammatory disorders of the female pelvis. AB - The use and importance of CT in the evaluation of patients who have inflammatory conditions of the pelvis has increased in recent years. Although its role may be limited in women of childbearing age, CT may provide definitive diagnostic information concerning benign pelvic masses frequently present in this age group. CT is particularly valuable in detecting infectious complications in the postpartum and postoperative pelvis. In patients who have known or suspected inflammatory conditions of the bowel, CT is the imaging modality of choice to identify extraluminal complications such as abscess formation. CT is frequently diagnostic in cases of diverticulitis and appendicitis and is of recognized value in guiding percutaneous drainage procedures, often sparing emergent surgical intervention. PMID- 1631289 TI - Computed tomography and magnetic resonance imaging of the female lower urinary tract. AB - Computed tomography (CT) and magnetic resonance (MR) imaging have become invaluable imaging modalities in the diagnosis of diseases involving the lower urinary tract. Both CT and MR imaging are able to accurately stage bladder carcinoma, with MR imaging able to distinguish between superficial and deep muscle invasion of tumor. CT and MR are also the studies of choice for evaluating retroperitoneal fibrosis, which often affects the urinary tract; MR imaging is often able to detect the presence of active inflammation and occasionally rule out a malignant cause. MR imaging holds promise for the evaluation of stress urinary incontinence and urethral disease. Although diseases of the distal ureter continue to be most accurately diagnosed by intravenous urography and retrograde studies, CT and MR imaging may serve a helpful secondary role. PMID- 1631290 TI - Method improves consistency in L5-S1 joint space films. AB - This article describes a new way to determine the correct angle of the central ray for radiography of the L5-S1 joint space in the lateral position. The methods described in the most widely used positioning textbooks do not result in consistent results. This article provides an easy-to-apply alternative. PMID- 1631291 TI - An analysis of radiographic repeat and reject rates. AB - A literature search of the past 20 years of publications on radiographic repeat/reject rates located 11 reports of 48 studies. A significant unpublished 12th report added a 49th. This article evaluates these studies to propose mean radiographer repeat/reject rates and reasons for economic uses in administrative evaluations. A comprehensive bibliography provides a resource for future repeat rate studies. PMID- 1631292 TI - Mobile mammography: the technologist's role. AB - This article discusses the role of the radiologic technologist in a mobile mammography screening program targeted at the economically disadvantaged in Dade County, Fla. It describes the development of process, structure and outcome standards used to guide and evaluate both the program and the radiologic technologist within this setting, highlighting the technologists' valuable contributions to the program. PMID- 1631293 TI - Radiolabeled antibodies in cancer treatment. AB - The use of radiolabeled antibodies may play a major role in future treatment of cancer patients, affecting procedural operations throughout both radiology and radiation therapy departments. Because of the number of different radioisotopes that may be used, education of medical personnel will be of critical importance. Adaptation of current radiology procedures may enhance this therapeutic modality. PMID- 1631294 TI - Nebulous nonocclusion. PMID- 1631295 TI - Will mammographers be ready? PMID- 1631296 TI - Faculty development for distance educators. PMID- 1631297 TI - GABAergic circuits in the mammalian retina. PMID- 1631298 TI - Development of GABAergic neurons in the mammalian retina. PMID- 1631299 TI - GABAergic circuits in the lateral geniculate nucleus of the cat. PMID- 1631300 TI - Inhibitory GABAergic control of visual signals at the lateral geniculate nucleus. PMID- 1631301 TI - The distribution and function of gamma-aminobutyric acid (GABA) in the superior colliculus. AB - Laminer analysis of the distribution of GABA and GAD in the superior colliculus has shown that the distribution pattern of GABA within the SC is similar in rabbit, cat, and guinea pig. The highest levels of GABA were found in the superficial gray layer (SGL), averaging 37-40 mmol/kg dry weight. The GABA concentrations in the deep layers were each only half that of the levels in the SGL. The concentrations of both GABA and GAD in the upper half of SGL are the same as those in the substantia nigra and medial forebrain bundle which have the highest amounts of GABA in the CNS. Denervation studies of the fibers projecting to SGL suggest that the GABA concentrated in the SGL is intrinsic to the layer. The results obtained from immunohistochemical and electron microscopic studies on the localization of GABA neurons corresponds well with the regional distribution pattern of GABA and GAD reported here. However, pharmacological and electrophysiological studies do not necessarily accord well with the GABA distribution studies because they indicate that there are many GABA sensitive neurons in both the SGL and DGL. To investigate the role of GABA in the SGL, the effect of GABA and its agonists and antagonists on neurotransmission in SGL has been studied in SC slices in a perfusion system. Bath applied GABA (100 microM to 1 mM) enhanced the amplitude of postsynaptic field potentials (PSP) in SGL in a dose-dependent fashion and at concentrations above 1 mM it depressed the PSP in a dose-dependent fashion. A similar response pattern was obtained with muscimol (0.1-10 microM excitation; greater than 10 microM inhibition). However (-) baclofen only inhibited the PSP. Bicuculline (1 microM) shifted the dose-response inhibitory curve of GABA to the right, while the excitatory effect was enhanced. These results indicate that GABA has an excitatory and inhibitory action on neurotransmission in the SGL. The nigro-tectal GABAergic fibers terminate in the intermediate and deep layers of SC. Inhibition of GABAergic activity in the SC causes irrepressible saccades made toward the center of the movement field while GABA activation delays and slows saccadic eye movements. Thus, GABA in the SC plays an important role in the control of eye movements. The same GABAergic projection is also related to the propagation of generalized seizures. There exist collicular neurons which suppress the propagation of seizures.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1631302 TI - GABAergic neurons and circuits in the pretectal nuclei and the accessory optic system of mammals. AB - Two classes of GABAergic cell bodies have been described. They probably can be divided into GABAergic local interneurons and GABAergic projection neurons. GABAergic cell bodies receive few terminals which is in contrast to non-GABAergic somata, which receive many synaptic contacts. GABAergic dendrites that originate from GABAergic cell bodies, however, receive numerous terminals, both GABAergic and nonGABAergic. It can therefore be concluded that somatic inhibition is not present on GABAergic neurons, but does occur on nonGABAergic neurons. Furthermore, dendrites traverse large parts of the NOT/DTN forming a complex network that enables sampling and integration from a wide area. The projection to the IO is not GABAergic itself, but cells projecting to the IO receive a substantial GABAergic input, that probably originates in part from the MTN. Further investigation on the distribution of this input over a completely identified neuron would provide the quantitative data that are required to verify the above mentioned hypothesis. A GABAergic projection that originates in the pretectal nuclei is directed towards the superficial layers of the SC in the cat (Appell and Behan, 1990) and rat (Van der Want et al., 1991). A second GABAergic projection derives from the pretectum and reaches the LGN (Cucchiaro et al., 1991). Whether this projection originates from the same GABAergic cell bodies that project to the SC and the LGN or is derived from different populations remains to be determined. The ultrastructural studies of the NOT/DTN complex have shown that GABAergic terminals with different morphological characteristics are present and that the GABA positive F and P terminals are widely distributed over somata and the adjacent neuropil. The P terminals probably originate from dendrites of GABAergic interneurons while the F types originate from GABAergic projection and interneurons (Van der Want and Nunes Cardozo, 1988). One of these sources is located in the MTN differ from the intrinsic GABAergic terminals with respect to their relation to R terminals. GABAergic MTN terminals were never observed to receive R terminal input. This is in contrast with other GABAergic terminals which frequently do receive direct contact from R terminals. Within glomeruli triadic arrangements, formed by a single retinal terminal, a dendritic profile and second axonal profile dendritic profile and second axonal profile synapsing with the dendrite, were frequently encountered in the OPN (Campbell and Lieberman, 1985), but only occasionally in the NOT/DTN (Nunes Cardozo and Van der Want, 1987).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1631303 TI - GABA in the retina and central visual system. PMID- 1631304 TI - The pathways and functions of GABA in the oculomotor system. PMID- 1631305 TI - GABA mediated inhibitory processes in the function of the geniculo-striate system. PMID- 1631306 TI - GABAergic networks of basket cells in the visual cortex. PMID- 1631307 TI - Lateral inhibitory interactions in areas 17 and 18 of the cat visual cortex. PMID- 1631308 TI - The synaptic inputs to simple cells of the cat visual cortex. PMID- 1631309 TI - GABA-mediated inhibition in the neural networks of visual cortex. PMID- 1631310 TI - Molecular properties of GABAergic local-circuit neurons in the mammalian visual cortex. PMID- 1631311 TI - Development of GABA-containing neurons in the visual cortex. PMID- 1631312 TI - Functional organization of GABAergic circuitry in ectotherm retinas. PMID- 1631313 TI - Investigation of higher order structures of proteins by ultraviolet resonance Raman spectroscopy. AB - Progress in laser technology and light detection devices have enabled us to explore protein structures and their dynamics by using time-resolved resonance Raman spectroscopy. It is in the last decade that Raman spectra of proteins excited at 200-240 nm have brought about rich structural information. The technological developments in deep UV resonance Raman spectroscopy are reviewed first, and the unique information on proteins obtainable from such spectra are summarized. As an application of this technique to investigations of the higher order structures of proteins, studies on the quaternary structure transition of haemoglobin are described. PMID- 1631314 TI - Experimental approaches to transduction and the receptor potential in muscle receptors. PMID- 1631315 TI - Computer simulation of 2D-NMR (NOESY) spectra and polypeptide structure determination. PMID- 1631316 TI - Effect of prostaglandin F2 alpha (PGF2 alpha) on sources of progesterone and pregnancy in intact, ovariectomized and hysterectomized 90-100 day pregnant ewes. AB - A single dose of 8 or 16 mg of PGF2 alpha per 58 kg body weight was injected intramuscular into intact, ovariectomized or hysterectomized 90-100 day pregnant sheep in three separate experiments. Both doses of PGF2 alpha decreased the weights of the corpora lutea (P less than or equal to 0.05) and the concentration of progesterone in ovarian venous plasma at 72 hr (P less than or equal to 0.05) compared to the 0 hr sample within treatment groups and to control ewes at 72 hr in intact and hysterectomized pregnant ewes. In hysterectomized pregnant ewes, progesterone in jugular plasma declined (P less than or equal to 0.05) from 0 to 72 hr but never fell below 4 mg/ml and this decrease in progesterone after 8 or 16 mg PGF2 alpha was greater than in control hysterectomized ewes (P less than or equal to 0.05). There was a significant decrease in progesterone over time in jugular or uterine venous plasma in the presence of absence of the ovaries in 90 100 day pregnant ewes (P less than or equal to 0.05) but the profiles of progesterone were not different between vehicle and PGF2 alpha-treated ewes (P greater than or equal to 0.05). Uterine venous progesterone never declined below 30 ng/ml in the presence or absence of the ovaries and there was a significant quadratic increase (P less than or equal to 0.05) in uterine venous progesterone toward the end of the 72 hr sampling period indicating an increase in steroidogenic activity of the placenta. PGF2 alpha did not affect the number of abortions in intact or ovariectomized pregnant ewes (P greater than 0.05). Thus, the corpus luteum of sheep at 90-100 days of pregnancy is functional and responsive to PGF2 alpha, placentomes are functional but do not appear to be responsive to the doses of PGF2 alpha tested and PGF2 alpha was not an abortifacient over the 72 hr treatment period. PMID- 1631317 TI - Adenosine facilitates the response to HCG, PGE1 or PGE2 and inhibits the response to PGF2 alpha by HCG-stimulated ovine luteal cells in vitro. AB - Dispersed ovine luteal cells collected on day 7 or 16 postestrus were incubated in vitro with hCG, PGE1 or PGE2 in the presence or absence of adenosine, dipyridamole (inhibitor of adenosine uptake) or PGF2 alpha in two separate experiments. Secretion of progesterone was increased by hCG, PGE1 or PGE2 when incubated with day 7 luteal cells (P less than or equal to 0.05) which was increased further when co-incubated with adenosine (P less than or equal to 0.05). PGF2 alpha alone or in the presence of hCG decreased (P less than or equal to 0.05) the secretion of progesterone by day 7 luteal cells, PGF2 alpha decreased post treatment cell viability with or without hCG (P less than or equal to 0.05) and adenosine reduced (P less than or equal to 0.05) the inhibitory effect of PGF2 alpha on hCG actions and luteal cell viability. Day 16 luteal cells were not functional based on jugular progesterone (P less than or equal to 0.05) and did not respond to hCG, PGE1, or PGE2 in the presence of adenosine or PGF2 alpha (P greater than or equal to 0.05). It is concluded that adenosine enhances the response of functional luteal cells to the luteotropins hCG, PGE1 or PGE2 and adenosine reduces the luteolytic response to PGF2 alpha by hCG stimulated ovine luteal cells in vitro. PMID- 1631318 TI - Effects of reactive oxygen species on eicosanoid metabolism in human endothelial cells. AB - The influence of reactive oxygen species (H2O2 was used as model substance) on the formation and release of PGI2 and TXA2 by cultured human endothelial cells was analyzed. In the presence of H2O2 concentrations which did not induce a general cell damage (analyzed by estimation of the cellular concentration of energy rich phosphates and extent of lipid peroxidation), the formation of both eicosanoids exhibited a sigmoidal shape with respect to time. Increasing H2O2 concentration shortened the half time of PGI2 and TXA2 production. The maximum rates of PGI2 and TXA2 formation were separated by a delay of the TXA2 production. The ratio of PGI2 and TXA2 formation was 100 to 1 at the time of maximum PGI2 formation and 1-2 to 1 at the time of maximum TXA2 formation. This effect of reactive oxygen species could contribute to the reduction of the protective function of the endothelium in hemostasis and vascular tone. Using antioxidants, the modulating function of reactive oxygen species on the eicosanoid metabolism in endothelial cells was verified. PMID- 1631319 TI - Specific and non specific stimulation of prostaglandin release by human skin fibroblasts in culture.--Are changes of membrane fluidity involved? AB - In order to study a bidirectional relationship between changes of membrane fluidity and prostaglandin synthesis, the arachidonic acid cascade was stimulated in cultured human skin fibroblasts by unspecific stimuli (hypotonicity, low calcium concentrations) and by the specific stimulus, bradykinin. Fluorescence anisotropy of trimethylammoniumdiphenylhexatriene was used to measure membrane fluidity in cell monolayers. Hypotonicity or low calcium concentrations induce membrane fluidisation and prostaglandin synthesis. However, after specific stimulation of prostaglandins with bradykinin (at normocalcic and isotonic conditions) a rigidification of plasma membranes was observed in living cells. Fluidisation of membranes and bradykinin activate phospholipase A2 and induce prostaglandin synthesis. Although in cell membrane preparations increased phospholipase A2 activity leads to fluidisation, in our model a membrane fluidisation was not observed after stimulation of phospholipase with bradykinin. This suggests that in living cells a fluidizing effect of lysolecithin resulting from phospholipase A2 activation may be rapidly counteracted by its removal. A decrease of phosphatidylcholin content and consequently a rigidification of the membrane may ensue. Thus, the cell culture model using two different ways of stimulating phospholipase activity, helps to define the directional relationship between changes of membrane fluidity and activation of phospholipase and the arachidonic acid cascade in living human cells. PMID- 1631320 TI - Repetition priming follows spontaneous but not prompted recognition of familiar faces. AB - Reaction times to make a familiarity decision to the faces of famous people were measured after recognition of the faces in a pre-training phase had occurred spontaneously or following prompting with a name or other cue. At test, reaction times to familiar faces that had been recognized spontaneously in the pre training phase were significantly facilitated relative to an unprimed comparison condition. Reaction times to familiar faces recognized only after prompting in the pre-training phase were not significantly facilitated. This was demonstrated both when a name prompt was used (Experiments 1 and 3) and when subjects were cued with brief semantic information (Experiment 2). Repetition priming was not found to depend on prior spontaneous recognition per se. In Experiment 3, spontaneously recognizing a familiar face did not prime subsequent familiarity judgements when the same face had only been identified following prompting on a prior encounter. In Experiment 4, recognition memory for faces recognized after cueing was found to be over 90% accurate. This indicates that prompted recognition does not yield repetition priming, even though subjects can remember the faces. A fusion of "face recognition unit" and "episodic record" accounts of the repetition priming effect may be more useful than either theory alone in explaining these results. PMID- 1631321 TI - On the relation between visual spatial attention and visual field asymmetries. AB - In the typical visual laterality experiment, words and letters are more rapidly and accurately identified in the right visual field than in the left. However, while such studies usually control fixation, the deployment of visual attention is rarely restricted. The present studies investigated the influence of visual attention on the visual field asymmetries normally observed in single-letter identification and lexical decision tasks. Attention was controlled using a peripheral cue that provided advance knowledge of the location of the forthcoming stimulus. The time period between the onset of the cue and the onset of the stimulus (Stimulus Onset Asynchrony--SOA) was varied, such that the time available for attention to focus upon the location was controlled. At short SOAs a right visual field advantage for identifying single letters and for making lexical decisions was apparent. However, at longer SOAs letters and words presented in the two visual fields were identified equally well. It is concluded that visual field advantages arise from an interaction of attentional and structural factors and that the attentional component in visual field asymmetries must be controlled in order to approximate more closely a true assessment of the relative functional capabilities of the right and left cerebral hemispheres. PMID- 1631322 TI - A sensorimotor basis for motor learning: evidence indicating specificity of practice. AB - Our previous work (Proteau, Marteniuk, Girouard, & Dugas, 1987) was concerned with determining whether with relatively extensive practice on a movement aiming task, as the skill theoretically starts becoming open-loop, there would be evidence for a decreasing emphasis on visual feedback for motor control. We eliminated vision of the moving limb after moderate and extensive practice and found that the movement became more dependent on this feedback with greater amounts of practice. In the present study, we wished to test the hypothesis, developed from our previous work, that at the base of movement learning is a sensorimotor representation that consists of integrated information from central processes and sensory feedback derived from previous experiences on the movement task. A strong test of this hypothesis would be the prediction that for an aiming task, the addition of vision, after moderate and relatively extensive practice without vision, would lead to an increasingly large movement decrement, relative to appropriate controls. We found good support for this prediction. From these and our previous results, and the idea of the sensorimotor representation underlying learning, we develop the idea that learning is specific to the conditions that prevail during skill acquisition. This has implications for the ideas of the generalized motor program and schema theory. PMID- 1631323 TI - The phonetic integration of speech and non-speech sounds: effects of perceived location. AB - The third-formant (F3) transition of a three-formant /da/ or /ga/ syllable was extracted and replaced by sine-wave transitions that followed the F3 centre frequency. The syllable without the F3 transition (base) was always presented at the left ear, and a /da/ (falling) or /ga/ (rising) sine-wave transition could be presented at either the left, the right, or both ears. The listeners perceived the base as a syllable, and the sine-wave transition as a non-speech whistle, which was lateralized near the left ear, the right ear, or the middle of the head, respectively. In Experiment 1, the sine-wave transition strongly influenced the identity of the syllable only when it was lateralized at the same ear as the base (left ear). Phonetic integration between the base and the transitions became weak, but was not completely eliminated, when the latter was perceived near the middle of the head or at the opposite ear as the base (right ear). The second experiment replicated these findings by using duplex stimuli in which the level of the sine-wave transitions was such that the subjects could not reliably tell whether a /da/ or a /ga/ transition was present at the same ear as the base. This condition was introduced in order to control for the possibility that the subjects could have identified the syallables by associating a rising or falling transition presented at the left ear with a /da/ or /ga/ percept. Alternative suggestions about the relation between speech and non-speech perceptual processes are discussed on the basis of these results. PMID- 1631324 TI - [The physician facing a diagnosis of bad prognosis. Considerations on the moment of certain mental discomfort]. PMID- 1631325 TI - [Anticipatory anxiety and interpersonal relations with the radiologist of patients undergoing diagnostic imaging]. AB - A pilot study has been carried out with the aim of evaluating the impact of updated imaging techniques (CT and MRI) versus "simple" examinations (tomography, X-rays, US, and nuclear medicine) on the anticipatory anxiety of the patients, as well as on the radiologist-patient relationship. Ninety consecutive patients undergoing diagnostic imaging modalities were examined according to the following schedule: 1) preliminary interview and anxiety assessment according to HRSA; 2) diagnostic imaging investigation, and 3) filling out an "ad hoc" questionnaire. The collected data have been divided into two groups: the "simple" group (52 patients submitted to X-rays, tomography, US, and nuclear medicine), and the "complex" group (38 patients submitted to CT and MRI). Anticipatory anxiety was observed in all subjects and attained psychopathological rates in more than half of them. Anxiety proved to be related to the completion of the examination rather than to its complexity. The questionnaire has pointed out the need for a more interactive relationship between radiologist and patient during diagnostic imaging examinations. PMID- 1631326 TI - [Combined use of real-time digital subtraction radioscopy and computerized tomography: potential advantages in diagnostic and interventional radiology]. AB - The idea of combining fluoroscopy and CT arose from the daily practice in diagnostic and interventional radiology. A Diasonics OEC high-performance image intensifier complete with a digital subtraction system was connected to a Siemens Somatom-DRH CT scanner to work in tandem. CT is used for a localization in-depth and fluoroscopy for the subsequent maneuvers within an organ or body compartment. With this combination, complex procedures such as transarterial portography, percutaneous embolizations, pain treatment and manipulation for catheterization of the bile ducts and urinary tract could be performed in one place and in one session. CTF is especially useful when patients should not be moved about from room to room or undergo an examination in several sessions, as it happens with children or critically ill or contagious patients. PMID- 1631327 TI - [Percutaneous treatment of bile duct lithiasis. Personal experience in the first 150 cases]. AB - Since 1983 we have percutaneously treated 150 cases of bile duct lithiasis in which previous endoscopic maneuvers had been incomplete or unfeasible. Complete resolution of lithiasis was obtained in 139 of 150 patients. In 6 cases only partial success was obtained but symptoms subsided. In 2 cases the treatment failed and the patients underwent surgery. Minor complications were observed in 12.6% of patients and resolved either spontaneously or by percutaneous maneuvers. Mortality rate was 2%. After a follow-up period of 6-12 months, 9 patients had a recurrence, completely resolved with further percutaneous treatment. These cases never required surgery. We obtained the best results in patients with stones residual after cholecystectomy or a iatrogenic stricture of the biliary tree. We obtained good results in massive lithiasis with combined endoscopic, surgical and radiological procedures. Morbidity and mortality rates were lower than in surgical series and similar to the endoscopic ones. The short hospitalization, the low cost and the possibility of treatment on an outpatient basis should promote the spreading of percutaneous techniques in the treatment of bile duct lithiasis. PMID- 1631329 TI - [Bone disease in multiple myeloma. A study of 237 cases]. AB - From 1984 to 1990 the authors reviewed the radiologic-clinical charts of 237 patients affected with multiple myeloma (MM). The series included 127 males and 110 females (mean age: 66 years) who had been classified according to Durie and Salmon clinical criteria. All the patients underwent X-rays of the skeleton, as recommended in international literature; moreover, 148 subjects underwent whole body bone scintigraphy, and 130 bone marrow scintigraphy. A selected group of cases (18 male/female patients) were submitted to bone densitometry employing both quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA). The results follow: 1) in the first stage of the disease, a high number of patients (29.5%) exhibits no skeletal abnormalities on X-rays; the most common lesion locations include the spine (49%), skull (35%), pelvis (34%), ribs (33%), humeri (22%), femora (13%) and mandible (10%); 2) the most frequent pattern is osteolysis, as a characteristic "punched-out" multiple lesion; the second most frequent lesion is osteopenia (43%), especially in the spine; pathologic fractures are common (54%) in the ribs, vertebral bodies, limbs; typical associations of features and sites are seen on X-ray images, which sometime make diagnosis easier; 3) whole-body scintigraphy, revealing aspecific uptake only in the presence of pathological fractures, is not recommended in the first staging of the disease, but is considered as a valuable technique in the follow-up, when the patients become symptomatic; 4) bone marrow scintigraphy, especially in the "marrow expansion" pattern, might be considered as an attempt made by the body to recover the central space which was destroyed by myelomatous involvement. The prognostic value of this technique is still to be assessed; 5) bone densitometry, by confirming the grade of osteopenia, reveals that osteoporosis is a peculiar pattern of bone disease in MM, which is not related to age only; 6) conventional radiography of the skeleton is the method of choice in the diagnosis of lytic areas of MM, and remains, as yet, irreplaceable. The other diagnostic techniques- i.e., CT and MRI--can be used to evaluate the extent of bone and soft tissue involvement, in the cases with questionable diagnosis, and to assess the degree of marrow involvement. PMID- 1631328 TI - [Loco-regional fibrinolysis in peripheral arterial bypasses. Our experience]. AB - Thirty-one patients (29 males and 2 females) with 34 thrombosed grafts were treated by direct intra-arterial infusion of urokinase; the lesions were acute in 27 cases and chronic (2-4 months) in 4. Urokinase was infused in doses of 50,000 UI/h. Angiographic follow-up exams were performed every 12 hours. The infusion was stopped when lumen patency was re-established and there was no significant mural thrombus or peripheral embolus. Treatment usually lasted 4-72 hours (average: 18 hours). The hematological status was controlled by measuring plasma fibrinogen, coagulation time, partial thromboplastin time, prothrombin and antiplasmin time. Initial success rate was 76% (23 patients). Overall 1-year patency was 56% in 23 cases: 85% in the patients with correctable lesions by means of surgery or PTA, and 46% in the patients with non-correctable lesions. After the first period, patency remained high in the patients followed up to 5 years. Our experience confirms that lysis of a thrombosed graft is possible by the local infusion of a low-dose fibrinolytic agent and exhibits high success rate and low complication rate in acute and chronic obstructions. PMID- 1631330 TI - [Magnetic resonance in the staging of multiple myeloma]. AB - The authors retrospectively reviewed the MR examinations of 46 patients with clinical and laboratory findings of monoclonal gammopathies (MG). All cases had been submitted to radiographic examination which had shown skeletal involvement in 22 cases and osteoporosis in 11, with rupture of the vertebral body in 3 patients. Scintigraphy had been performed on all patients and CT on 12; 36 patients were subsequently submitted to follow-up (at 6, 12 and 24 months). MR examinations were performed with dedicated coils and standard sequences for the subjects with skeletal localizations on X-ray images. The extant cases, with no radiographic evidence of skeletal involvement, were submitted to MRI of the spine, skull and pelvis. In agreement with clinical and laboratory findings and with follow-up results (in 36 patients), MRI diagnosed MG with no skeletal involvement in 13 cases, osteoporosis in 8 (with rupture of the vertebral body in 2), asymptomatic non-progressive myeloma in 4, solitary myeloma in 3, and multiple myeloma in 18 cases. The good identification of bone marrow and its multiplanarity make MRI the method of choice in the study of patients with suspected or known gammopathies. If compared with other modalities, MRI is more sensitive and accurate in depicting the tumor, its size and relationship to periskeletal tissues, and its possible multifocality. Moreover, the technique has proven to be a valid tool during the follow-up, showing tumor response to therapy. PMID- 1631331 TI - [Computerized tomography of the orbit in Graves' ophthalmopathy. New observations]. AB - In order to evaluate Graves' ophthalmopathy new CT parameters have been introduced such as: the diameters of the five extraocular muscles, the value of their addition, the grade of apical crowding, the enlargement of optic nerve sheaths and of the superior ophthalmic vein, and the anterior displacement of the lacrimal gland. On this subject we report our further experience after reviewing 68 cases in which the new ocular parameters were correlated with altered ocular motility and optic neuropathy. The results confirmed our previous study, dealing with several groups of patients, which at the moment seem to be 2, instead of 3 groups: a) patients with increase in both muscular and fatty tissue (54/68 cases); b) patients with main or exclusive increase in fatty tissue (14/68 cases). Relevant clinical signs were present only in the first group of patients, where the medial, inferior and superior muscles were affected in 53/55, 53/55 and 50/55 cases respectively. A muscle increase by nearly 50% was more frequently found in cases with altered ocular motility, an increase by 90% was often associated with optic neuropathy. In case of optic neuropathy apical crowding was often observed, mainly in coronal scans, together with significant enlargement of the optic nerve sheath and of the superior ophthalmic vein. As to proptosis, preseptal area and anterior displacement of the lacrimal gland, they demonstrated lower correlation with the reference symptoms, even though their occurrence was high in symptomatic patients. PMID- 1631332 TI - [Inherent problems of the use of magnetic resonance in patients with metallic implants currently used in orthopedic practice]. AB - Forty-eight patients with oncologic prosthetic devices (modular rotatory shoulder, Kotz, custom made) and metallic means of fixation (Sherman's plates, Ender's rods, etc.) underwent MRI in order to: 1) assess possible physical changes in the magnetic field or the alloys under examination; 2) detect the presence and type of artifacts, and 3) verify the onset of eventual noxious effects of the alloy on the patient. The diagnostic investigation was preceded by an experimental phase which was characterized by: A) a study of the temperature fluctuations of the alloys when submitted to the magnetic field and to radiofrequency; B) the identification and characterization of the artifacts, as well as C) their physical interpretation. During examination, there was no evidence of any mobilization of the means of fixation, sensation of endogenous heat, or other subjective complaints on the part of the patient. The authors observed that, even in the presence of artifacts, MRI provided good evaluation of the soft tissues around the devices by identifying tumor recurrences in the presence of an oncological prosthesis. MRI was also capable of showing trophic changes in the tissues surrounding the means of fixation. Thus, the method exhibits no contraindications in the study of these patients but, on the other hand, does not allow the evaluation of the integrity or mobilization of the prosthetic devices. PMID- 1631333 TI - [Accuracy of magnetic resonance (0.5 T) in traumatic lesions of the knee. Controlled 87 cases]. AB - In this study the authors investigated the diagnostic accuracy of Magnetic Resonance (MR) imaging as a method to recognise traumatic disorders of the knee; in particular its capability to identify meniscal and cruciate ligaments tears was examined. The results have been compared with those from arthroscopy and/or surgery, which were considered the gold standard of the study. Eighty-seven consecutive patients with suspected traumatic injury of the knee were prospectively studied. All patients underwent MR examination (0.5 Tesla magnet, gradient echo sequences, slices thickness = 5 mm) and, within 15 days/1 month, arthroscopy or surgery. The high diagnostic accuracy (internal meniscus = 87.5%; external meniscus = 88.5%; anterior cruciate ligament = 93.1%; posterior cruciate ligament = 96.5%) has confirmed the good diagnostic capabilities of MR in assessing traumatic lesions of the knee. PMID- 1631334 TI - [Normal anatomy and findings in traumatic pathology of the popliteal system. A MR study]. AB - To date, the lesions of the popliteal system, which are responsible for the so called postero-lateral knee instability, are still an imperfectly known chapter of knee conditions. We retrospectively analyzed 215 consecutive MR examinations performed May-August 1991 to evaluate MR capabilities in correctly depicting both the normal anatomy and the pathologic conditions of the popliteal system. Using our standard protocols for knee study and two different magnets (0.064 and 0.5 T), we identified 23 lesions of the popliteus and of its meniscal and peritoneal insertions, and 17 lesions involving also other capsular and ligamentous structures of the knee. Coronal T1-weighted images were the best ones to correctly identify normal knee anatomy, whereas sagittal T2-weighted images were more sensitive in detecting popliteal lesions. Our results had clinical or surgical confirmation in all cases. PMID- 1631335 TI - [Computerized tomography as a diagnostic complement of standard radiograms in the evaluation of traumatic lesions of the carpal scaphoid. A study of 10 cases]. AB - The authors investigated the value of direct coronal CT as a diagnostic complement to plain radiography in the assessment of post-traumatic scaphoid conditions. The series included 10 patients who were selected either for disagreement of clinical and radiological findings, the latter being negative (3 patients), or for better assessment of radiological findings, which had diagnosed bone lesions, in order to plan treatment (7 cases). CT provided additional information in 5 patients, demonstrating 2 nonunited fractures in the first group and 2 pseudoarthroses with no significant bone deformity and 1 osteonecrosis in the second group. These results, which proved essential to plan the subsequent treatment, show that CT has, at present, in specific cases, a definite role in evaluating post-traumatic scaphoid conditions, and stress the value of direct coronal images, which are both easy to interpret, being equivalent to radiographs in postero-anterior projection, and quick to perform. PMID- 1631336 TI - [Pelvic fractures]. AB - Pelvic fractures, although accounting for only 2-3% of all traumatic skeletal lesions, are extremely important due to the frequent sequelae and complications that can cause the death of the patient. Moreover, their incidence is increasing due to road accidents, sport and work injuries. X-ray examinations, if correctly performed, allow the degree of residual stability of the pelvic ring to be assessed; they allow both the recognition of the mechanisms of injury and the evaluation of bone lesions. The X-ray examination can provide the orthopedist all the necessary information for the correct treatment planning, employing an external setting or, when the lesion is unstable, an open-field setting. The authors, after considering the major types of pelvic ring fractures, classified on the basis of the mechanisms of injury, suggest the best radiologic protocol, in their opinion, for the pelvic fractures whose diagnosis is based on X-ray examinations. In these cases, CT is less useful than in the study of acetabular fractures; it rarely provides additional information and thus remains a supplemental exam to X-rays. PMID- 1631337 TI - [Diagnostic contribution of CT in implantology: use of a new Denta-Scan reconstruction program]. AB - The authors report their preliminary experience with the use of a new CT reconstruction program: Denta-Scan. Tomodensitometric studies of both the maxillary and the mandibular bones are actually mandatory for the planning of the correct implantation techniques. Denta-Scan, usually employed for CT studies in implantology and maxillo-facial surgery, suits to both pre- and postoperative evaluations. It provides accurate anatomical imaging, identifying details and landmarks which are helpful for surgical planning. Moreover, it allows TDM evaluation of bone structures, showing the presence of pathologic conditions potentially affecting the result of implantology. In the postoperative follow-up Denta-Scan allows to verify the correct positioning of the prosthetic implant, testing its integration in the bone structure as well as the rate of surgical failure. PMID- 1631338 TI - [Echographic evaluation of pancreatic dimensions in type 1 diabetes mellitus]. AB - Aim of this study was to determine whether pancreatic size is altered in patients suffering from type I diabetes mellitus. Twenty-five diabetics (14 males and 11 females) and twenty-five healthy controls entered the study. All patients and controls were scanned by the same operator with the same US equipment after overnight fasting. The longitudinal and antero-posterior diameters of the head, body and tail and the transverse diameter of the head as well as the total area of the gland were measured through longitudinal and axial scans. The two groups were homogeneous relative to age, sex, distribution, height, weight and body mass index. All measured diameters as well as the total area of the gland were significantly smaller in diabetic patients than in controls (1-way ANOVA: p less than 0.001). These results may open new perspectives to US identification of possible changes in pancreatic size by a new US study including high-risk subjects without clinical signs. PMID- 1631339 TI - [Hepatobiliary ascaridiasis in childhood: echographic diagnosis]. AB - Ascaris lumbricoides infestation in the liver and biliary tract causes various clinical manifestations due to the migration of larvae and adult organisms. Parasites in the bile ducts cause obstruction and such complications as cholecystitis, cholangitis and liver abscesses. We report the US findings of biliary ascaridiasis as observed in a series of 13 children over a 3-year period. The patients (6 females and 7 males) presented hepatosplenomegaly, abdominal distension, right subcostal pain; 3 of 13 exhibited subicteric features and fever. The US features of Ascaris lumbricoides infestation are: hyperechoic linear images due to parasites within the dilated bile ducts, target images; mobile hyperechoic linear images within the gallbladder; intrahepatic abscesses with different features and sizes. Microscopic sections of hepatic tissue show inflammatory infiltration around the Ascaris eggs. Emergency surgery is sometimes to be performed. The value of US, as we assessed it, has been already stressed by other authors. PMID- 1631340 TI - [Preoperative staging and recurrence of rectal tumors. Comparison of transrectal ultrasonography and magnetic resonance]. AB - The accuracy of transrectal US (TRUS) and of MRI was evaluated in the preoperative staging and in local recurrences of rectal cancers. Fifty-four patients were examined: 45, with known rectal cancer, for preoperative staging, and 9 for the evaluation of local recurrences. Nineteen patients were examined with MRI in basal conditions, 21 after rectal air enema and 5 after paramagnetic contrast enema (Gd-DTPA). The following parameters were evaluated for preoperative staging: wall infiltration, invasion of perirectal fat and adjacent structures, lymph node involvement. Morphologic and signal intensity (on MRI) changes were evaluated for the diagnosis of local recurrences. TRUS provided 2 false positives. In the same patients, basal MRI results were poor, owing to difficult demonstration of the different wall layers, while in the patients studied after air enema, the lesion was hyperintense. In 20 patients with a fat infiltrating tumor, TRUS provided 3 false negatives and 2 false positives; basal MRI yielded poor results, while air enema and paramagnetic contrast enema clearly demonstrated all fat-infiltrating lesions, with only one false positive. PMID- 1631341 TI - [Echography in gynecologic emergencies]. AB - The authors report their experience with US in gynecologic emergencies through a retrospective study on 105 patients presenting with acute abdomen of suspected gynecologic nature. The series included 3 groups of patients: Group I: 59 patients all submitted to immediate surgery. The following pathologic conditions were observed: ectopic pregnancy (23 cases), torsion or hemorrhage from ovarian cysts (13 cases), pyosalpinx or tubo-ovarian abscess (9 cases), torsion of pedunculated uterine leiomyoma (7 cases), intraperitoneal bleeding from hemorrhagic corpus luteum (6 cases), hematocolpos and hematometra from imperforate hymen (3 cases). Two false positives, not included in this group, resulting from appendicular abscesses and misinterpreted as ovarian, were submitted to surgery in a gynecologic unit. Group II: 19 patients treated with medical therapy for the following conditions: torsion or hemorrhage from hyperstimulated ovary (10 cases), pyosalpinx or tubo-ovarian abscess (9 cases). Group III: 25 patients in whom neither US nor clinical examination revealed positive gynecologic findings. Both US and clinical follow-up were negative in these patients. The study was aimed at evaluating the role of US in identifying both lesion and peritoneal involvement, and in the diagnosis of nature. US proved a valuable tool in the first two diagnostic steps, allowing to confirm/dismiss active pathologic conditions, to indicate the medical/surgical treatment (immediate or delayed), to detect associated pathologies to study with further examinations. As for lesion nature, US alone proved poorly useful if not correlated with an accurate clinical history. PMID- 1631342 TI - [Exclusive radiotherapy in the treatment of carcinoma of the portio cervicis, stage IIB FIGO]. AB - From January 1970 through December 1987, 135 patients with cervical cancer in stage IIB (FIGO criteria) were treated by means of exclusive radiotherapy in the Istituto del Radio of the Brescia University. Thirty cases were treated by exclusive external-beam radiotherapy (RTT), 39 by brachytherapy (CU) plus external-beam radiotherapy, 24 by combined RTT and CU, 41 by RTT + CU + RTT, and 1 case by CU alone. Crude survival at 5 years is 52.4%, and NED survival is 50%. The differences between the values of crude and NED survival by radiotherapy technique were statistically significant (p 0.05), ranging from 69.8% in the RTT + CU group to 35.5% in the RTT alone group. Twenty-four cases (18%) failed to obtain complete remission, and 24 more cases recurred in the pelvis. Sequelae were evaluated by the French-Italian glossary; they were present in 62 cases (46%), but in 12 cases only (9%) they were severe. The incidence of sequelae was highest in the groups of patients treated with the combined techniques (RTT and CU) which allowed best disease control. PMID- 1631343 TI - [A rare complication of renal and biliary lithotripsy: subcapsular hematoma of the liver]. PMID- 1631344 TI - [Positioning of stent in urethral stenosis caused by carcinoma of the prostate]. PMID- 1631345 TI - [Acute abdomen following dislocation of transhepatic-duodenal biliary drainage. Resolution by use of percutaneous perihepatic drainage]. PMID- 1631346 TI - [Spontaneous dissection of the extracranial internal carotid artery: an atypical angiographic finding]. PMID- 1631347 TI - [Association of idiopathic pulmonary fibrosis and emphysema. An instructive case]. PMID- 1631348 TI - [Ultrasonographic study of tubercular effusions. Apropos of 12 cases]. PMID- 1631349 TI - [A rare case of concomitant duplication of the inferior vena cava with azygous vein continuation. MR aspects]. PMID- 1631350 TI - [Epidermoid cysts arising in the proximity of the left vaginal wall]. PMID- 1631351 TI - Dietary pesticide risk assessment. AB - In this review, the process of dietary pesticide risk assessment has been presented and three major components of the process--estimation of pesticide residue levels, estimation of food consumption patterns, and characterization of risk based on a comparison of exposure estimates with toxicological criteria- have been identified. Each component of the process is subject to considerable uncertainty that may compromise the accuracy of the final risk assessment. In estimating pesticide residue levels, common practices range from highly theoretical models assuming that all residues are present at a predetermined level (typically at the tolerance level) to the use of market basket survey data obtained at the time the food is ready for consumption. Intermediate techniques include using actual monitoring data (usually obtained from government residue enforcement programs) and/or making corrections to estimates on the basis of actual pesticide use. Additional corrections may be used to incorporate data on the effects of post-harvest practices such as processing, washing, cooking, peeling, and transportation that have often been shown to dramatically reduce residue levels, although occasional increases in residue levels and/or formation of toxicologically significant breakdown products may also result from post harvest practices. Food consumption estimates are typically derived from national surveys of consumer food consumption behavior and are also subject to considerable uncertainty. Food consumption estimates are often disaggregated into distinct population subgroups based on age, gender, geographic region, and ethnicity, although the accuracy of estimates for particular subgroups is commonly questioned on the basis of the adequacy of sample size. At the present time, data from the 1977-78 Nationwide Food Consumption Survey are still being used, and the incorporation of more recent data from the 1987-88 Nationwide Food Consumption Survey is being delayed due to major flaws in the study. On occasion, other food consumption surveys may be used, although they are typically much smaller in scope than the 1977-78 and 1987-88 studies and are considered less reliable. The multiplication of residue level estimates by food consumption estimates yields an estimate of human pesticide exposure. Commonly, the theoretical maximum residue contribution (TMRC) is calculated that represents the maximum "legal" exposure to pesticides. Calculation of the TMRC involves the assumptions that all pesticides legally allowed on a particular commodity will always be applied, that all residues are present at the tolerance levels, and that there are no post-harvest effects on residue levels. Often the TMRC is used as a sorting tool by the EPA in its preliminary assessment of dietary risks to pesticides.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1631352 TI - Aflatoxins in animal and human health. AB - Aflatoxins remain as a threat to the health of livestock as well as humans by their continuing intermittent occurrence in both feeds and foods. The finding that aflatoxin-contaminated feeds, and eventually purified aflatoxins, were carcinogenic in rats and trout initiated a multitude of studies in search of the role of these toxins in human liver disease, especially cancer. Although aflatoxins have caused acute liver disease in humans, epidemiologic evidence of the involvement of aflatoxins in PLC has not been clarified. Earlier studies did not consider that the hepatitis B virus (HBV) may have contributed to the PLC in the selected populations. Although later studies that did include measurement of the HBV antigen in serum provided conflicting evidence for the role of aflatoxin in PLC in these populations, the latest and most comprehensive study found no association between aflatoxin exposure and PLC mortality. The technological advances and findings of the chemical, immunologic, and metabolic activities of aflatoxins such as binding to DNA and protein to form adducts, development of monoclonal antibodies, and mutational specificity of the genotoxic compounds will, it is hoped, help to clarify the role of aflatoxin as a risk factor, among many others, in the development of primary liver cancer in humans. Aflatoxicosis of animals is usually manifested by pathologic changes in the liver, but they have been found to be carcinogenic and teratogenic as well as causing impaired protein formation, coagulation, weight gains, and immunity. The importance of the carcinogenic effect in livestock is diminished because they are not fed contaminated diets for a sufficient time prior to marketing for slaughter. Animals are variably susceptible to aflatoxins, depending on such factors as age, species, breed, sex, nutrition, and certain stresses. Swine, cattle, and poultry are the domestic species of greatest economic concern in terms of aflatoxicosis. In all species, the evidence of disease is a general unthriftiness and reduction in weight gains, feed efficiency, immunity, and production. More conclusive evidence of aflatoxin involvement in disease includes acute to chronic liver disease with concomitant increases in specific liver enzymes in the serum. In cattle, milk production is affected, but of greater significance is that the aflatoxins in feeds can be rather efficiently converted to toxic metabolites in milk, with even small amounts being readily detectable. The poultry industry probably suffers greater economic loss than any of the livestock industries because of the greater susceptibility of their species to aflatoxins than other species.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1631353 TI - [Hypofibrinolysis in coronary artery disease and predisposing conditions]. PMID- 1631354 TI - [Brucellar sacroiliitis. A detailed review with an analysis of treatment efficacy]. AB - All patients diagnosed of brucellosis in 4 regional hospitals during a period of nine years were reviewed, in an attempt to evaluate the efficacy of different antimicrobic regimens and also the clinical features. Evolution and complications of brucellar sacroiliitis. Of a total of 548 patients, 12% had been diagnosed of sacroiliitis and, of theme, 49 had complete data available with efficacy of different treatments, the time elapsed until fever and pain ceased was evaluated, together with initial therapeutic failures, relapses and length of hospital stay. Brucellar sacroiliitis is the most frequent osteoarthral complication of Brucella sp. in our setting. Keeping an stable incidence. It is predominant among young male (82%) population (mean age 25 +/- 12 years). The illness evolution is acute and less frequently subacute with a evolution mean-time before referral of 38 +/- 44 days (minimum 4 days, maximum 180 days). Fever (81%) and pain on gluteus and low lumbar localizations (100%) are the more frequent clinical features. Time elapsed until pain ceased was longer with doxycycline plus rifampicin (68 +/- 86) than with doxycycline plus streptomycin (28 +/- 43) (less than 0.05) and length of hospital stay was also longer with said treatment (p less than 0.05). There were no differences concerning time frame until fever ceased, initial therapy failures and relapses. Sequelae are infrequent and consist in persistency of pain. In resume response to treatment with usual regimens, doxycycline plus streptomycin of doxycycline rifampicin is good, being however time elapsed until pain ceases of mean length in hospital stay shorter in the group receiving doxycycline plus streptomycin. Control studies to confirm these data are need. PMID- 1631355 TI - [Abdominal tuberculosis today. A review of 46 cases]. AB - The clinical features, radiological and therapeutic response of 46 cases of abdominal tuberculosis (AT) seen at a university hospital are presented. Diagnosis was anatomopathologic in 39 cases (85%) and clinical with response to tuberculostatic in 7 cases (15%). Most of the patients did not have history nor exposition to tuberculosis. Both sexes were similar affected, mean age 43 years old, between 11 and 79. Clinical manifestations were no specific, the most frequent fever (65%), abdominal pain (63%) and constitutional syndrome with asthenia, anorexia and weight loss (63%). Thorax radiograph was normal in 50% and PPD negative in 42%, so in 10% of patients both tests were negative. More than half of the patients had other disease. 82% of patients were cured with tuberculostatic. 18% of patients died. AT seen now is different from classic descriptions. Is not a complication of pulmonary tuberculosis (PT) as it was to be in the past. Thinking in AT only in patients with PT make most patients lead without diagnosis. PMID- 1631356 TI - [Coxiella burnetii osteoarthritis]. AB - A case of a 25-year-old female characterized by febrile osteoarthritis and arthromyalgias as the only clinical manifestation of a Q fever is discussed. Analytical data were compatible with those of an acute inflammation and serologic findings reached diagnostic levels. Response to Doxycycline treatment was totally satisfactory. Even though associated arthromyalgias are described in some cases of Q fever as well as sporadic cases of osteoarthal infection due to Coxiella burnetii, there are no oligosymptomatic cases published as the one discussed. Some physiopathologic considerations referred to this peculiar onset are suggested. PMID- 1631357 TI - [The fasciitis-polyarthritis syndrome]. AB - A 56 years old woman showed polyarthritis with thickness and retraction of the palmar fascia: 5 months later an undifferentiated ovarian carcinoma was diagnosed. Symptoms improved when antineoplastic chemotherapy was started. This has been called fasciitis-polyarthritis syndrome. Cases published on the scientific literature are reviewed, discussion their etiopathology and the possibility of establishing an early diagnosis of neoplasia through the finding of this association. PMID- 1631358 TI - [Sneddon's syndrome: its clinical characteristics and etiopathogenic factors]. AB - Sneddon syndrome is know as the association of idiopathic livedo reticularis and cerebrovascular lesions. The most characteristic trait of this syndromes is a non inflammatory arteriopathy in medium caliber vessels. The pathogenic role of antiphospholipid antibodies in this disease is not clear. Clinical characteristics and etiopathogenic features of eight patients with Sneddon's syndrome are reviewed, specially regarding its relationship with primary antiphospholipid syndrome. A female predominance was found (3:1) as well as a relationship with hypertension (five patients suffered hypertension), but no relation was found with contraceptive use. Three patients showed evidence of antiphospholipid antibodies, present as anticardiolipin antibodies with significative titers in three cases and lupus anticoagulant in one. Digital artery biopsy performed in four patients showed in all of them the pathologic features characteristic of this disease. Seven patients were treated with platelet activity inhibitors and one with oral anticoagulants. Six of them have had a year and half follow-up without showing any new ischemic stroke. The main etiopathogenic factor on Sneddon's syndrome is the presence of a non-inflammatory arteriopathy in medium caliber vessels. Blood hypertension and antiphospholipid antibodies could play a role in the development of cerebrovascular lesions in some cases. No relationship has been found with oral contraceptives in this series of patients. Medium term prognosis with platelet activity inhibitors therapy seems benign. PMID- 1631359 TI - [Eosinophilia and ascites as an expression of a subserous form of eosinophilic gastroenteritis]. AB - Clinical and biological features are discussed on a 50 years old female, who suffered a peritonitis with eosinophilic ascites, together with a bilateral pleural effusion with the same cytologic findings, developing in the course of an hypereosinophilia. The clinical situations in which eosinophilic ascites is associated with blood hypereosinophilia are reviewed. The histopathological findings in this case support the diagnosis of eosinophilic gastroenteritis of subserous type. PMID- 1631360 TI - [Multifocal tubercular osteitis in a female patient infected with the human immunodeficiency virus]. AB - We discuss the case of a 22-year-old female, carrying of antibodies to against human immunodeficiency virus (HIV), who developed several tumors on different bone localizations, which corresponded to plurifocal bone tuberculosis. We reviewed multifocal bone tuberculosis reports in the literature. The exceptionally of this case in underlined and the relationship between this atypical clinical presentation and immunodeficiency in discussed. PMID- 1631361 TI - [The treatment of AIDS and its associated pathology]. AB - A distinction has to be made in the treatment of the acquired immune deficiency syndrome (AIDS), on one hand there is the treatment of the associated pathology that these patients suffer when their immune system is unable to cope with diseases such as opportunistic infections and neoplasms; on the other there is the treatment of the human immune deficiency virus (HIV) itself. In this work we review the state-of-the-art of both therapies, paying special attention to the treatment of opportunistic infections, because they hold responsibility for the deaths in 80% to 90% of these patients; the importance of the concept of prophylactic treatment, primary as well as secondary, in these diseases is outlined. The treatment of associated neoplasms has a worse outcome. Finally the antiviral therapies against HIV itself, are discussed, paying special attention to zidovudine (AZT) and didexosinosine, two of the more currently widely used drugs in the treatment of these patients. We end with the review of combined therapy, which probably will become, in the next future, the solution in the treatment of this disease. PMID- 1631362 TI - [Hypertransaminasemia of probable toxic origin]. PMID- 1631363 TI - [Should Hodgkin's disease be considered a diagnostic criterion of AIDS?]. PMID- 1631364 TI - [Hypoglycemia secondary to tenoxicam]. PMID- 1631365 TI - [The different attitudes of cancer patients and their relatives facing diagnostic information]. PMID- 1631366 TI - [Cardiac tamponade as the first manifestation of neoplastic disease]. PMID- 1631367 TI - [Left pleural effusion due to a transdiaphragmatic abdominothoracic communication in a cirrhotic patient with ascites]. PMID- 1631368 TI - [Fournier's gangrene in a diabetic woman: apropos a case]. PMID- 1631369 TI - [Adrenal hemorrhage linked to systemic lupus erythematosus associated with the antiphospholipid syndrome]. PMID- 1631370 TI - [Chylous ascites associated with hepatic fibrosis]. PMID- 1631371 TI - [Antiparasitic medication in a Spanish hospital: the needs of the year 2000]. PMID- 1631372 TI - [Tuberous sclerosis: apropos a case with a late presentation]. PMID- 1631373 TI - [Brucellosis: a clinico-serological study in a rural health area]. AB - We analyze retrospectively 132 cases of brucellosis evaluating the performance of diagnostic procedures, complications and serological and clinical evolution. We compare the 74 patients treated with streptomycin plus tetracycline versus the 41 patients treated with doxycycline plus rifampicin. The more outstanding results we find: a) Great sensibility of the rose bengal test; b) Higher relapse rate in the more severe cases (p less than 0.01); c) Good evolution with scarce relapse rate in both treatment groups; agglutination titers were lower at one year in the group treated with doxycycline plus rifampicin (p less than 0.05). CONCLUSIONS: Both treatments showed good efficacy, controlled studies would be needed to determine the most adequate one. PMID- 1631374 TI - Deaths from poisoning in Barcelona (Spain), 1986-1989. AB - Between 1986 and 1989, 3226 violent deaths were recorded in Barcelona, 489 of which were due to poisoning. The yearly distribution of these 489 deaths was: 1986, 74; 1987, 98; 1988, 134; and 1989, 183. Of all poisoning deaths, 316 were due to narcotic opiates use, 54 to the inhalation of toxic gases, 49 to the use of psychoactive agents, 37 to caustic products and the others 33 cases to various toxic agents (insecticides, methanol, solvents, mushrooms, etc.). Opioid use is currently the leading cause of death by poisoning in Barcelona, and affects a young population with a mean age between 25 and 27 years. In the groups corresponding to toxic gases and psychoactive drugs, the mean ages are 48 and 45.7 years, respectively. The oldest population was found in the group where death was caused by caustic agents, where the mean age is 56.5 years. The male sex was predominant in all groups except that of caustic agents, where 56.8% of the victims were women. This study confirms the notable increase in opiate- related deaths in the city of Barcelona (up from 27 cases in 1987 to 158 in 1989) and shows stability in the numbers for the other groups. Among the different hypotheses concerning of this remarkable increase in deaths related to opiate use, the aging of consumers and changes in the purity or composition of the product seem to be the most probable. PMID- 1631376 TI - [Prescription of temporary sick leave to pregnant women in the absence of legal provisions]. AB - Swiss legislation doesn't provide any maternity leave for pregnant women before the day of delivery. A retrospective study of 550 women who had just delivered, showed that in the absence of such provisions, 48.9% of women who worked during their pregnancy had been given temporary sick leaves by their physician on one or more occasion. The decision of giving such sick leave depends primarily on whether or not the woman presents obstetrical risks and is not systematic. The frequency of sick leaves increases also with job load. Finally, the attitude of each woman, related to her personal characteristics, her degree of satisfaction at work and her job security, are other deciding factors for prescribing sick leave. PMID- 1631375 TI - [Risk factors in cardiovascular diseases in a semi-urban community of the Tunisian Sahel]. AB - Cardiovascular diseases are the leading cause of mortality in the western countries at the same time they are beginning to appear with increasing frequency in developing countries. An epidemiologic study was carried out at Kalaa Kebira (Sousse-Tunisia) to determine the prevalence of the different risk factors of cardiovascular diseases. The study was performed on a representative sample of 555 adults of 20 years and more (response rate of 76%). There was a high proportion of adult males smokers (66%). The prevalence of hypertension varied from 15% to 25%, those of diabetes was 6.5%. An hypercholesterolemia greater than 6.2 mmole/l was observed for 12% of the sample and obesity for 20%. PMID- 1631377 TI - Self-reported smoking and exercising behaviours during the postnatal period: assessing congruence between spouses. AB - The aim of the study was to assess the congruence between women's self-reported behaviours during the postnatal period and the answers provided by their husbands. One hundred nineteen couples participated. Firstly, women reported their own smoking and exercising behaviours for four months following childbirth. Subsequently, husbands evaluated their spouses' behaviours over the same period of time. Smoking behaviour was assessed on 5-category scale ranging from non smoker to daily smoker whereas physical activity was measured on a 6-category scale ranging from no physical activity to regular physical activity. The polychoric correlation coefficients and the weighted Kappa indexes indicated that the degree of congruence between respondent pairs were appropriate, but better for smoking than exercising. The results of the present study support the idea that the information obtained from spouses can be helpful in the assessment of the reliability of the answers provided by their live-in partner, particularly in surveys regarding smoking. PMID- 1631378 TI - [Mortality due to suicide, accidents and undetermined causes in hospitalized mental patients 1968-1982]. AB - An analysis of the national statistics on mortality in psychiatric hospitals, covering 14 years from 1968 to 1982, provided rates of deaths by suicides, accidents and ill-defined symptoms (chapters 16 and 17 in the ICD). Death rates among psychiatric inpatients are compared to rates in the general population. For suicide, there is an increase of about 45% in patients under 75, which is higher than for the general population. The evolution for accidents is close to that found in the general population. The death rate by ill-defined symptoms is decreasing. The increase in the rates of deaths by suicide found both in France and in several other countries suggests that the major changes (sectorization policy and use of psychotropic drugs), in the care lead to increased risk of suicide for certain patients due to shortened hospital stays and subsequent intermittent institutional care. Specific modes of death can also be described: senility without mention of psychosis, airway obstruction by false passages, notably in subjects under 55, accidental falls, hangings and drownings are particularly important in the observed over-mortality. PMID- 1631379 TI - Decline of accident mortality in childhood, Italy, 1955-1984. PMID- 1631380 TI - [Occupational medicine in Morocco. Current status and future perspectives]. PMID- 1631381 TI - Epidemiology and prevalence of seropositivity against Borrelia burgdorferi antigen in La Rioja, Spain. AB - The aim of this study was to acquire a better knowledge of the epidemiology of Lyme disease. A seroepidemiologic study was made by evaluating the different levels of antibodies to Borrelia burgdorferi in a five hundred serum representative sample of a population from the province of La Rioja, Spain. Samples were randomly selected and stratified to take into account sex, age, rural or urban residence, and geographical area. All subjects included in the study were asked to fill out a questionnaire containing this information along with data concerning leisure activities, occupation, contact with animals, tick bite and antecedent features related to Lyme disease. No statistical differences were found in relation to sex or age. The seroprevalence was very high (31.3%) in mountain areas, where Ixodes ricinus and deer are present. The risk factors associated with seropositivity were forestry and cattle-raising activities, as well as contact with animals. The best titer of antibodies associated with clinical antecedents of Lyme disease and related disorders was 1/256. PMID- 1631382 TI - [Influence of educational status on a screening test for dementia, the Mini Mental State Examination]. AB - This study aimed to examine the relationships between the educational level and the Mini-Mental State Examination (MMSE) total scores and its different items. In a survey dealing with cerebral aging, the MMSE administered 2,792 subjects aged 65 years and over, who continued to live at home. The total score decreased with age and increased markedly when the educational level rose. The proportion of failures was higher than or equal to 10% for 12 of the 30 MMSE items, including the 5 items designed to measure attention ability (serial subtractions) and the 3 ones exploring delayed memory. Regarding these 12 items, the percentage of failures increased homogeneously with age, but the relationship with educational level was heterogeneous: it was very strong for the calculation items, weaker for the delayed memory items. These results pointed to the complex relationships between MMSE scores and educational level, and suggested a possible bias related to the screening tool in dementia surveys. PMID- 1631383 TI - [A mid-term clinical and hemodynamic evaluation of the Wessex and Hancock II bioprostheses]. AB - The purpose of this study is to compare clinically and hemodynamically the Wessex and Hancock II porcine bioprostheses. We compared functional class and data from echo-Doppler in 34 Wessex bioprostheses (group A) with those in 42 Hancock II bioprostheses (group B). We subdivided group A into A1 and A2. A1 was made up of 23 Wessex manufactured since 1986. A2 constituted 11 Wessex made before 1986 which belonged to a series with some variations in the manufacturing process, and in which some early dysfunctions have been described. We compared data from these sub-groups between each other as well as with those of group B. The groups were homogeneous in age, sex, patients body surface and the time elapsed since the prosthetic implant. The mean mitral gradient, the mitral area, the peak aortic gradient and the regurgitation incidence were similar in groups A and B. In A2 the mean mitral gradient was significantly superior to that of group B (7.1 +/- 1.1 mmHg vs 5.4 +/- 1.4 mmHg; p less than 0.01), and the mitral area showed a tendency to be inferior, although with no statistical significance. The functional class of the patients was similar in all the groups. We conclude that the Wessex bioprosthesis presents hemodynamic data and functional class similar to those of the Hancock II, with the exception of a sub-group of Wessex manufactured before 1986 which presents mean mitral gradients superior to the others and which would warrant further studies. PMID- 1631384 TI - [Myocardial infarct in the geriatric patient: the short- and mid-term prognostic factors]. AB - The purpose of this study was to investigate the clinical features and the prognostic factors related to early and late mortality in the acute myocardial infarction (AMI) in the geriatric population. We have studied 208 consecutive patients with AMI admitted to the Coronary Care Unit at the Hospital General de Asturias. Two groups were selected: group A included 102 patients older than 65 years; and 106 were younger (group B). In the group A was found a significantly lower percentage of males (52.9% vs 89.6%; p less than 0.0001) and smokers (45.1% vs 89.6%; p less than 0.0001); and older patients showed a greater incidence of diabetes mellitus (30.7% vs 16%; p less than 0.01). In the geriatric group, the clinical course of AMI is characterized by a greater incidence of heart failure (50% vs 29.2%; p less than 0.002) and cardiogenic shock (22.5% vs 7.5%; p = 0.002). Early mortality (first month) was significantly higher in elderly patients (36.3% vs 7.5%; p less than 0.001); and this increased mortality rate is partially related to an increased incidence of heart pump failure, despite having a smaller enzymatic infarct size by CPK peak (1,062 +/- 1,017 U/l vs 1,579 +/- 1,428 U/l; p less than 0.005). The multivariate analysis by stepwise logistic regression, selected diabetes mellitus, heart failure and peri-infarct bundle branch blocks as the only independent predictive variables for the early mortality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1631385 TI - [Color-coded Doppler in the diagnosis of vascular complications following heart catheterization]. AB - To determine the value of color Doppler in the diagnosis of vascular complications resulting from cardiac catheterization 5 consecutive patients, with the clinical suspicious of vascular iatrogenesis potentially requiring surgical repair, were analyzed. In 2 patients a femoral mass developed after a diagnostic catheterization but 3 patients underwent previously an interventional catheterization technique. In 3 patients color Doppler readily visualized a systolic jet originated in the femoral artery entering an anterior echo-free cavity, and a reversal flow in diastole, suggesting a femoral pseudoaneurysm. In 1 patient the clinical diagnosis of arteriovenous fistulae was confirmed by color Doppler which demonstrated a continuous turbulent flow within the femoral vein. In the remaining patient a diagnosis of simple femoral haematoma was made after the demonstration of a relatively echogenic structure overlying the femoral artery and vein but not interfering with their flows. In the 3 patients with femoral pseudoaneurysms and in the patient with arteriovenous fistulae the diagnosis was confirmed by angiography and during surgery. Our preliminary findings underscore the value of color Doppler, using the technology currently available in echocardiographic laboratories, in the differential diagnosis of vascular complications after cardiac catheterization. PMID- 1631386 TI - [The value of isotopic ventriculography in the prognosis and follow-up of patients undergoing dynamic myocardioplasty]. AB - Dynamic cardiomyoplasty was performed in twenty patients with dilated cardiomyopathy. The electrical stimulation was produced by a double chambered pacemaker. Patients were studied by nuclear ventriculography one week before surgery, in the immediate postoperative phase and 8 or 12 months later. Five patients died (four of them were operative deaths). In this group the left ventricular ejection fraction (LVEF) was lower than in survivors (22 +/- 8% vs 28 +/- 4%; p less than 0.001). The end-diastolic volume and the mitral regurgitation index were greater (200 +/- 76 ml/m2 vs 153 +/- 34 ml/m2; p less than 0.001 and 2.12 +/- 0.75 vs 1.68 +/- 0.54; p less than 0.001, respectively). The immediate effect of cardiomyoplasty was the significative reduction in the contractility. However, at 8 or 12 months of follow-up, the LVEF increased in the 72% of the survivors. The end-diastolic volume and the regurgitation index decreased significantly. The clinical status improved in the 81% of the survivors. The best results were obtained in those patients in which a pulse train stimulation was employed in the training phase. Nevertheless, the changes in LVEF are not consistent with the improvement in the clinical status. The improve in the cardiac performance should be also due to the reduction in the left ventricular diameters and in the mitral functional regurgitation. PMID- 1631387 TI - [The usefulness of isotopic ventriculography in the follow-up of left ventricular dysfunction]. PMID- 1631388 TI - [The present, future, reality and fiction of cardiomyoplasty]. PMID- 1631389 TI - [Biventricular functional adaptation during a prolonged race. An analysis of global and regional ventricular function]. AB - To determine the effects of a six-hour competitive race on left and right ventricular performance, 99mTc gated blood pool scans were performed to 6 long distance runners before the race (rest), each hour during the race and one hour after concluding the exercise (recovery). Heart rate increased during the race, peaking at 4th hour of competition (55 +/- 3 to 110 +/- 9 lpm; p = 0.001). Evolution of right ventricular ejection fraction showed a similar behavior with the evolution of left ventricular ejection fraction during the competition (r = 0.39; p = 0.006). Blood volume in the lungs increased at the end of the race (index 1.13 +/- 0.14) normalizing at recovery (index 1.03 +/- 0.03). Left and right ventricular peak filling rate had an inverse correlation with pulmonary blood volume (r = -0.31; p = 0.041 and r = -0.47; p = 0.001 respectively). Both left and right ventricular ejection fraction had an inverse correlation with pulmonary blood volume (r = -0.38; p = 0.006 and r = -0.34; p = 0.01 respectively). The anteroseptal regional ejection fraction showed an inverse correlation with end-systolic and end-diastolic volume (r = -0.32; p = 0.03 and r = -0.4; p less than 0.01 respectively). The posterolateral region showed a parallel evolution with the global ejection fraction for both left and right ventricles (r = 0.57; p less than 0.0001 and r = 0.38; p = 0.009 respectively). In conclusion, a transient biventricular functional adaptation during a prolonged race is related to pulmonary blood volume redistribution and to a higher preload for both ventricles and a greater afterload for the right ventricle. The posterolateral and inferoapical regions show a similar behavior as both left and right ventricular ejection fraction, response that does not occur with the anteroseptal regional ejection fraction. PMID- 1631390 TI - [Diverticulum of the right ventricle with dilated myocardiopathy]. AB - We report on a newborn infant with right ventricular diverticulum associated to dilated myocardiopathy, who was diagnosed by two-dimensional echocardiography within 24 hours after vaginal delivery. We believe this case represents the youngest one ever diagnosed with this disease. PMID- 1631391 TI - [An aortobronchial fistula 11 years after the resection of a posttraumatic aortic aneurysm]. AB - A case of a 47-year-old white male who developed an aortobronchial fistula eleven years after resection of a posttraumatic aneurysm of the descending aorta is presented. The clinical picture, the diagnostic problems as well as the treatment are presented and commented. PMID- 1631393 TI - The need for advocating specialized care. PMID- 1631392 TI - [A diffuse pulmonary hemorrhage following thrombolytic therapy in an acute myocardial infarct]. AB - A sixty-years-old man was admitted to the hospital because of acute myocardial infarction of anterior location. He had four episodes of ventricular fibrillation each requiring defibrillation and short-term cardiopulmonary resuscitation (less than 10 minutes). He was then managed with thrombolytic therapy, therapeutic doses of heparin and aspirin. He had persistent haemoptysis, chest X-ray revealing a diffuse bilateral alveolar infiltration. There was a continuous decrease in hemoglobin and hematocrit levels, with an evident clinical radiographic dissociation. Right cardiac catheterisation showed a normal left ventricular function. The single breath carbon monoxide diffusing capacity (DLCOsb) was high, indicative of a diffuse intrapulmonary haemorrhage causing the alveolar infiltration. PMID- 1631394 TI - Fatigue in multiple sclerosis: guidelines for nursing care. AB - Fatigue is a common chronic symptom of multiple sclerosis (MS) that can have disabling effects on the patient's quality of life. The cause of this fatigue is unknown, and there is no specific treatment for it. This article presents the major problem areas and manifestations associated with fatigue and incorporates suggested guidelines for the rehabilitation nurse to use in helping patients with MS manage this symptom. Major symptom areas include (a) physiological problems, (b) affective/behavioral/cognitive problems, and (c) environmental problems. Comprehensive intervention is addressed and the concept of fatigue as a nursing diagnosis is presented. PMID- 1631395 TI - A pediatric rehabilitation experience for undergraduate nursing students. AB - Pediatric rehabilitation is a specialty that will need more nurses in the future. A clinical rotation in this specialty was incorporated into the pediatric experience of junior-year baccalaureate nursing students at the University of Maryland School of Nursing. The experience helped students to learn more about the nursing care involved in pediatric rehabilitation, to appreciate the different disciplines within the specialty, and to view pediatric nursing from a holistic long-range perspective. The experience also strengthened ties between nursing education and practice. PMID- 1631396 TI - Managing crisis in a rehabilitation facility. AB - When crisis occurs in a healthcare facility, it involves not only the individual and his or her family, but also staff and management personnel--and personnel often are as disoriented and confused by crisis as is the individual. Healthcare providers, trained to manage the crises of others, are often at a loss when confronted with crisis in their own facility. The purpose of this article is to provide an outline of a strategy rehabilitation managers can follow in the event of a crisis in their facility. PMID- 1631397 TI - The evolution of rehabilitation facilities for children. AB - This article describes the development of rehabilitation facilities for children in the United States. The historical beginnings and subsequent growth of agencies nationwide that provide a variety of rehabilitative services for the pediatric population (birth to 21 years) are described. The origin of many of the modern day rehabilitation centers for all ages is seen in the founding of "homes" and other facilities for children during the late 19th and early 20th centuries. As the 21st century approaches, it is important to reflect on how far pediatric rehabilitation has come and project its continued growth and expansion through the year 2000. PMID- 1631398 TI - Restoring childhood through rehabilitation. AB - Nine-year-old Alesha's symptoms began with tingling in her hands, and within a few months she could neither walk nor talk. Alesha has Wilson's disease, a rare genetic condition that results in a progressive buildup of copper in the body. Alesha lost 2 years of her life to Wilson's disease. This article focuses on the clinical and rehabilitation aspects of Wilson's disease and on the efforts to restore to Alesha the childhood the disease cost her. Nursing care for Alesha involved physiological, developmental, and restorative components, with special attention to the home pediatric rehabilitation program. PMID- 1631399 TI - Deep vein thrombosis in the rehabilitation client. AB - Deep vein thrombosis (DVT) is a potentially life-threatening problem for both medical and surgical patients. The rehabilitation client is at high risk of developing DVT. Conditions such as spinal cord injury, paraplegia, cerebrovascular accident, and total hip replacement place patients at risk for developing DVT. Unfortunately, few articles that address nursing interventions for this problem in the rehabilitation population have been written. This article examines the scope of the problem and its causes, pathogenesis, risk factors, and signs and symptoms from a rehabilitation nursing perspective. PMID- 1631400 TI - A lesson from Mr. C. PMID- 1631401 TI - Early detection of pulmonary embolism. PMID- 1631402 TI - Clonal deletion and anergy: from models to reality. Introduction. PMID- 1631403 TI - A lifetime's flirtation with repertoire purging. PMID- 1631404 TI - Mechanisms and meaning of B-lymphocyte tolerance. PMID- 1631405 TI - Analysis of B-cell tolerance in mice expressing transgenic anti-CD8.2 immunoglobulin M molecules. PMID- 1631406 TI - The parameters of B-cell inactivation in transgenic mice vs classical model studies. PMID- 1631407 TI - Can self/nonself discrimination be explained entirely by clonal deletion? PMID- 1631408 TI - What is the mechanism of induction of intrathymic tolerance? PMID- 1631409 TI - Peptide-mediated anergy in human CD4+ T cells. PMID- 1631410 TI - Tolerance to peripheral antigens must involve non-deletional mechanisms. PMID- 1631411 TI - Peripheral tolerance. PMID- 1631413 TI - T cells causing immunological disease: immunopathology or autoimmunity? PMID- 1631412 TI - Deletion versus anergy: the superantigen paradigm. PMID- 1631414 TI - Post-thymic T-cell tolerance or indifference: that is the question. PMID- 1631415 TI - Was everyone a "little bit right" after all? PMID- 1631416 TI - The self/nonself discrimination: reconstructing a cabbage from sauerkraut. PMID- 1631417 TI - Clonal deletion, anergy and immunosuppression are connected in series to guarantee self-tolerance. PMID- 1631418 TI - Some reasons why deletion and anergy do not satisfactorily account for natural tolerance. PMID- 1631419 TI - [Temperament and freedom: biological foundations of the free will]. PMID- 1631420 TI - [Bone marrow graft in hereditary diseases]. AB - Since 1968, bone marrow transplantation became the first line therapy for selected metabolic and immunological hereditary disorders. Actually, advances in the supportive care in bone marrow transplantation and a better knowledge of the immunology of BMT complications has been associated with a better disease correction and an increase in long term survival. New approaches are under investigation and include: hematopoietic growth factors, enzymatic replacement and gene therapy. However at the present time BMT is still the only curative treatment for selected hereditary disorders. PMID- 1631421 TI - [Psychological adaptation to bone marrow transplantation]. AB - Bone marrow transplantation, used with increasing success over the past ten years, is recognized as highly stressful. Physiological and psychological rehabilitation after treatment is often difficult. This paper outlines the psychological issues encountered by adult patients with haematological malignancies through a review of the adjustment disorders associated with bone marrow transplantation, their prevalence, symptomatology and predictive factors. Some guidelines are proposed for the prevention of the stresses associated with hospitalization. PMID- 1631422 TI - [Pulmonary nodule and Osler-Rendu disease]. PMID- 1631423 TI - [Biocompatible materials and prostheses]. PMID- 1631424 TI - [Technique and indications for total hip prosthesis]. PMID- 1631425 TI - [Complications in total hip prostheses]. PMID- 1631426 TI - [Hip prosthesis: the anesthesiologist's point of view]. PMID- 1631427 TI - [Functional readaptation in the hospital after total hip prosthesis]. PMID- 1631428 TI - [Development of a protocol for the education of stoma patients]. PMID- 1631429 TI - [Total hip prosthesis, a diversified practice]. PMID- 1631430 TI - [Liver, bile ducts (1), cholecystectomy (anatomical data)]. PMID- 1631431 TI - [Blood derivatives (2)]. PMID- 1631432 TI - [The textile industry serving the operating bloc. Barrier textiles and double faced adhesive film]. PMID- 1631433 TI - [Anatomy and physiology of the hip joint]. PMID- 1631435 TI - [Complications of total knee replacements]. PMID- 1631434 TI - [Total sliding knee replacement: technique of insertion]. PMID- 1631436 TI - [Knee prosthesis: rehabilitation in the hospital service]. PMID- 1631437 TI - [Preoperative nursing care]. PMID- 1631438 TI - [The patient in the operating suite]. PMID- 1631439 TI - [Role of the circulating nurse and the scrub nurse]. PMID- 1631440 TI - [Role of the nurse anesthetist]. PMID- 1631441 TI - [Postoperative nursing care]. PMID- 1631442 TI - [Total knee replacement. A still difficult intervention]. PMID- 1631443 TI - [Treatment of pain in pediatric surgery]. PMID- 1631444 TI - [Anatomo-physiological review of the knee]. PMID- 1631445 TI - [ What is your diagnosis? Adenovirus pneumonia]. PMID- 1631446 TI - [Antibiotic therapy in ambulatory surgery]. AB - Antibiotic therapy in outpatient surgical care is reviewed. In the first section some skin and soft-tissue infections are discussed, where antibiotics are likely to achieve clinical cure. In the second section we examine, where surgical treatment alone is essential for successful eradication of the infection. Wound management, where antibiotics are still controversial, is mentioned in the last section. Some pharmacological data on the discussed antibiotics are given. PMID- 1631447 TI - [Assessment and treatment of minor cranio-cerebral injuries]. AB - Despite the usually uncomplicated course, minor head injury has a major economic impact because of its high frequency. The traditional evaluation and management using plain skull x-rays and subsequent surveillance has recently been questioned due to the wide-spread availability of CT and MRI. Indication and value of these diagnostic methods, however, are still ill-defined. The resulting uncertainty leads to increasing pressure on the smaller hospitals to transfer patients with minor head injury to specialized centres. This trend causes further financial escalation and the capacity of the specialized centres is not large enough to admit all minor injuries. The present review is focused on the initial risk estimation after minor head injury with the aim to derive guidelines for safe and efficient patient management. Adequately communicating patients without history of loss of consciousness have only a minimum risk of an intracranial haemorrhage and need not routinely be submitted to x-ray studies or in-hospital surveillance. Patients with a history of change of consciousness carry a risk of a few percent to develop intracranial haemorrhage and need therefore be admitted for 24 hours. A skull fracture increases the risk of haemorrhage to approximately 10%. An initially unsuspicious CT-scan is no absolute guarantee against subsequent intracranial haemorrhage. Patients who are disoriented and/or somnolent upon emergency room admission or who display a focal neurological deficit have a high risk of intracranial haemorrhage and emergency CT-scan is therefore recommended. The expensive MRI technique is not justified for initial diagnostic work up of head injuries. However, this technique represents a sensitive means to define organic lesions in cases of persistent neurological or neuropsychological deficits. PMID- 1631448 TI - [Acute deterioration of the CO diffusion capacity following exposure to ski-wax vapors]. AB - In cross country skiing use of hot wax is of importance. 90% of the active swiss cross country skiers have their own, self maintained equipment. Long unprotected exposure to hot wax fumes may cause disturbance of lung function. To examine short lasting disturbance in pulmonary function, CO-diffusion capacity and dynamic and static lung volumes in five healthy human subjects after exposure for one hour to hot wax (containing Paraffin and Cera-F) were determined. The subjects complained about burning eyes and tears, sore throat and coughing. Immediately after exposure all subjects showed a significant decrease of the CO diffusion capacity of 10.6% (SEM 3.9), related to the ventilated alveolar space (DCOSB/VA). Maximal decrease of 13.6% (SEM 2.4) was after 90 min. After 24 hours the reduction persisted with 9.4% (SEM 2.1). The dynamic and static lung volumes remained unchanged. In summary a reduction of the CO-diffusion capacity after inhalative hot wax exposure was observed for at least 24 hours. PMID- 1631449 TI - [An insulin-dependent diabetes patient with bloody diarrhea]. PMID- 1631450 TI - [A case from practice (247). Amnesic disorders in vertebral artery occlusion and arterial hypertension]. PMID- 1631451 TI - [What is your diagnosis? Infectious mononucleosis. Synonyms: Pfeiffer's glandular fever, kissing disease, monocytic angina]. PMID- 1631452 TI - [Gallstones: etiology and risk factors]. AB - Cholesterin is excreted into bile together with phospholipids and bile acids, which are essential for the formation of micelles. Cholesterin-supersaturation of the bile and a relative hyposecretion of bile acids, the presence resp. the lack of promotors and inhibitors of nucleation and a reduced gallbladder contractility are the most important factors in the formation of cholesterol stones. For the formation of pigment stones, however, an increase of bilirubin production and infection of the biliary tract are the causative factors. PMID- 1631453 TI - [Gallstones: natural course and complications]. AB - Cholelithiasis is a common clinical situation. In most individuals it takes an inconspicuous clinical course. In symptomatic patients the complications have to be considered: acute cholecystitis, cholangitis, choledocholithiasis, pancreatitis, ileus by large stones and--in a subgroup of patients--carcinoma of the biliary system. Therapy is warranted in symptomatic patients in order to prevent complications. The decision for use of surgical versus non surgical interventions is decided on a individual basis. In general laparoscopic cholecystectomy is the procedure of choice nowadays. A prophylactic cholecystectomy is as a rule not indicated in asymptomatic patients. PMID- 1631454 TI - [Drug therapy of gallstone disease]. AB - Cholesterol stones in the gallbladder can be dissolved in 60 to 90% by oral administration of chenodeoxycholic acid, ursodeoxycholic acid or the combination of both. The effect depend on the number and size of stones. Treatment is without any side effects and lethality. A great number and large stones can be dissolved by direct instillation of methyl-tert-butyl-ether (MTBE) into the gallbladder using the percutaneous transhepatic method. The success rate amounts to 90%, the average therapy duration is 9 hours. Solvents for chemolitholysis of pigmented stones are being tested. PMID- 1631455 TI - [Biliary extracorporeal shock-wave lithotripsy]. AB - Since 1985/86, more than 200 patients with problematic intra- and extrahepatic bile duct stones were treated with ESWL. Results are excellent and comparable with ESWL's success-story in urinary stone disease, abandoning widely open surgery for bile duct stones. In gallbladder-stone treatment, ESWL (always combined with bile acid litholysis) is only promising or successful in a carefully selected subset (10 to 15%) of all symptomatic patients (with good gallbladder contractility, limited stone volume and sonolucent stones). PMID- 1631456 TI - [Percutaneous and trans-papillary cholangioscopy: current diagnostic and therapeutic possibilities]. AB - Peroral and transhepatic cholangioscopy represent a substantial enrichment of the diagnostic and therapeutic spectrum in gastroenterology. The use of cholangioscopy in the diagnostics of hepato-biliary disease seems to make especially sense in those cases where ERCP, sonography and CT do not lead to a sufficient clarification of the pathological findings and inspection, biopsy and cytology are required. An essential field of application for cholangioscopy consists today in the lithotripsy of giant common bile duct stones where laser lithotripsy means an important progress in the complication-free removal of these concrements. Percutaneous-transhepatic cholangioscopy as the more invasive procedure is especially indicated in those cases where due to former operations or special anatomical situations the endoscopic retrograde access is difficult or impossible. Further fields of application like endoluminal ultrasound via miniaturized probes or photodynamic diagnostics and photodynamic therapy (PDT) of cholangiocarcinoma seem to be valuable aims for the future. PMID- 1631457 TI - [How can the AIDS virus outsmart our immune system?]. PMID- 1631458 TI - [How to interpret signals of an ultrasonic study: normal ultrasonic anatomy of the upper abdomen]. PMID- 1631459 TI - [Anal incontinence: practical approach]. PMID- 1631460 TI - [Can gastroduodenal lesions induced by non-steroidal anti-inflammatory agents be prevented?]. PMID- 1631461 TI - [Viral hepatitis C]. PMID- 1631462 TI - [Antibiotic-induced diarrhea and its prevention]. PMID- 1631463 TI - [Role of biosynthetic growth hormone in the nutritional management of adults]. PMID- 1631464 TI - [Asthma, allergy, current issues. Report of the "3A" of 10/26/1991: asthma and eosinophils]. PMID- 1631465 TI - [Management of chronic neurologic patients: apropos of patients with severe cerebrovascular involvement]. AB - We present clinical date and follow up in a rehabilitation unit with a multidisciplinary team for twenty two old patients with severe cerebrovascular disease. The patients were fully examined in the "Service de neurologie de Lausanne". New cerebral vascular accidents occurred in three patients. The other patients improved in functional status evaluated by the Barthel-Index in spite of no significant changes in neurological and neuropsychological status. PMID- 1631466 TI - [Prognosis in brain stem infarction]. AB - A retrospective study of patients who suffered cerebrovascular accidents (CVA particularly brainstem damage) was conducted to look for risk factors which, present on admission, indicated the chance of survival. The evolution of 100 patients, hospitalized in the Neurology Department, University Hospital Lausanne, after having had their first CVA was studied. The risk factors chosen were age, sex, hypertension, smoker, late onset diabetes, hypercholesterolemia as well as the conscious state, the location of the lesion and whether it was bi- or unilateral. Analysis of the data was performed by means of a stepwise multiple logistic regression program. The results demonstrated that diabetes or bilateral lesions, regardless of their position in the brainstem, or the combination of these two factors, indicated an unfavorable outcome, associated with a short term mortality rate greater than 30%. In their absence and despite the presence of the other risk factors, it was less than 2%. At one month the mortality rate was shown to be very high. At two month it was non insignificant and thereafter it became similar to that of the Swiss population. Brainstem lesions extending to the vital centres or respiratory complications related to the state of dependence were the most common causes of short term deaths. At long term the aetiology of death was the same as for the population as a whole. CONCLUSION: The results obtained show the importance of the prevention and treatment of patients at risk of CVA, particularly diabetes. To avoid the fatal complications, that arise from severe handicap in bedridden patients, the management must be rapid and efficient (physiotherapy and drugs). PMID- 1631467 TI - [Continuous infusion of a mixture of propofol, alfentanyl and atracurium in current anesthesiology practice. Apropos of 50 cases]. PMID- 1631468 TI - [Individualized care in the care of the many]. PMID- 1631469 TI - [Disaster plan of Geneva airport]. PMID- 1631470 TI - [Dudgeon's sphygmograph (1881)]. PMID- 1631471 TI - [HIV epidemic: an end to exceptional regulation? Response to the article which appeared under this title in the Revue medicale de la Suisse romande (112, 239 241, 1991)]. PMID- 1631472 TI - [Evaluation of the endometrium in postmenopausal women by means of vaginal ultrasound]. AB - In the context of a prospective study, the authors carried out vaginal ultrasound examinations at the Gynecology-Obstetrics Clinic of Gottingen University of two groups of post-menopausal women: 233 women with hemorrhage and 539 who were asymptomatic. A diagnostic curettage was carried out in cases where the endometrium had a depth of at least 4 mm. The authors identified a 6% incidence of cases of adenomatous hyperplasia, 21% of endometrial cancer in women with hemorrhages and a 20% cancer rate in the asymptomatic women. Where the thickness of the endometrium was less than 4 mm, there were no cases of cancer. The infiltration depth examined microscopically was twice as great in the patients with hemorrhages (10 mm vs 4 mm). PMID- 1631473 TI - [Endometriosis and sterility: whom to treat and how?]. AB - The difficulty in evaluating the efficacy of treatments for endometriosis in terms of sterility results from the frequent confusion between the inhibition of the natural progression of endometriosis and a beneficial effect on fertility. The authors review the supposed benefits and the drawbacks of the various medical and surgical treatments available and medically assisted fertilization (IVF) in the context of the various types of endometriosis damage. They highlight the inadequacy of the AFS score, which gives very similar scores for effects with widely differing impacts on fertility. The authors attempt to identify the therapeutic associations which seem currently to be useful in treating endometriosis and also beneficial in obtaining a pregnancy. PMID- 1631474 TI - [The Hellp syndrome. Clinical and laboratory test results]. AB - The Hellp syndrome is a complication of toxemia. It may occur before, during or after childbirth and may not be accompanied by any sign of toxemia. The main clinical sign is pain in the hepatic region. Haptoglobin is the most reliable parameter to demonstrate hemolysis, which is one of the disorders related to this syndrome. In the authors' opinion, early diagnosis and immediate delivery by Cesarean are the appropriate methods to use to reduce maternal and perinatal mortality. Conservative treatment is not generally effective and is dangerous. PMID- 1631475 TI - [Diagnostic and prognostic value of umbilical and cerebral Doppler velocimetry in intrauterine growth retardation]. AB - The diagnostic and prognostic value of Doppler velocimetry in delayed intrauterine growth was investigated in a series of 105 abnormal pregnancies. The diagnostic value of the umbilical Doppler velocimetry, whether alone or combined with simultaneous exploration of the umbilical and cerebral vessels was very limited. In contrast, the simultaneous exploration of the umbilical and cerebral vessels was of considerable prognostic value, since with regard to the risk of fetal distress, the sensitivity was 86.6%, the specificity 80% and the positive predictive value 63%. The negative predictive value was 95% and the prevalence 28.5%. The authors' experience also confirms the prognostic seriousness of the absence of diastolic flow or of reverse flow (2 perinatal deaths out of 6 cases). The interval between the changes in Doppler velocimetry and fetal distress is variable, however, ranging from two days to three weeks or more in these cases. PMID- 1631476 TI - [Cancer of the endometrium caused by antiestrogens]. AB - Tamoxifen is the most widely used non-steroidal antiestrogen compound for adjuvant treatment of postmenopausal breast cancer. Tamoxifen has both antiestrogen and estrogen-agonistic activity, which depends on the target tissue involved owing its systemic distribution. Upon the endometrium the agonistic estrogenic effect, so-called "paradoxical" effect, is suggested to induce proliferative changes such as hyperplasia or carcinoma. The authors report four cases of endometrial cancer developed in postmenopausal patients with breast cancer receiving tamoxifen. According to the literature data, the relationship of the tamoxifen to the endometrial remains uncertain: women with breast cancer are at increased risk for this neoplasm sharing common aetiologic hormonal factors and, in most published case reports, the uterine cavity has not been checked up before starting tamoxifen administration. PMID- 1631477 TI - [Intravaginal echography at the beginning of pregnancy]. AB - Endocavity ultrasound during the first three months of pregnancy provides greater detail in a number of obstetrical fields. In most cases, endocavitary ultrasound is not simply a way of "gaining time" in comparison with conventional transabdominal ultrasound (time saved estimated to be one week). In some cases it is also offers a definite "extra". Two areas of interest are focussed on particularly by the authors: 1) the fetal appendages (vitelline sac, membranes, extra-embryonic coelom, trophoblast) which may be detected or revealed in greater detail by endovaginal ultrasound, make it possible to get a picture of the embryology of the fetus and of the prognosis of the pregnancy. The combination of color coded Doppler corroborates this new approach to the fetus; 2) the developments of this "sono-embryology" makes it possible to identify certain fetal malformations at a very early stage (neuro-medullary, parietal malformations...). However, interpreting the morphology of the fetus examined during the first three months must remain prudent and is no substitute for the morphological ultrasound scan carried out at about four and one half months of pregnancy. PMID- 1631478 TI - [Tubal sterility. What treatment to propose: IVF or surgery?]. AB - The results of IVF in cases of tubal sterility are compared with those of surgery (macro- or micro-surgery, coelio-surgery). This analysis includes a continuous series of 1051 attempted pregnancies in 640 women (with or mixed tubal sterility with or without endometriosis). After an average 1.64 attempts per patient, 220 women had achieved 241 pregnancies (pregnancy rate: 22.9% per puncture, 34.3% per woman). Of these 241 pregnancies, there were 172 (71.8%) which continued to term, 57 (23.6%) miscarriages and 11 (4.6%) ectopic pregnancies. The pregnancies carried to term were single pregnancies in 129 cases (74.6%), twin pregnancies in 37 cases (21.4%) and triple pregnancies in 7 cases (4%). The indication of coelio surgery (or microsurgery) is justified in young women with no history of genital tuberculosis, tubal plasty or ectopic pregnancy and presenting with purely tubal sterility with a good prognosis. Restoration of patency after tubal sterilization remains a good indication for microsurgery in young women. In all other cases, indication is for IVF from the outset. PMID- 1631479 TI - [Efficacy and acceptability of dexfenfluramine in women consulting in gynecology. 336 overweight patients treated for 3 months]. AB - The efficacy on bodyweight and the acceptability of a three month treatment with dexfenfluramine (Isomeride), combined with a prescribed diet, were evaluated in 336 women followed by a gynecologist for overweight. These women were divided into three groups, those in the sexually active age group (80%) and perimenopausal and post-menopausal women (20%) and had the following characteristics: mean bodyweight 80.2 +/- 0.6 kg; excess bodyweight 35.0 +/- 0.5% of theoretical ideal weight, mean bodyweight index = 30.6 +/- 0.2 kg/m2. Simultaneously with the weight loss, a study of the change in gynecological symptoms was carried out at each consultation and for each group. Investigation of the bodyweight showed that 80% of the patient who followed the treatment for three months lost weight, the mean loss being 7.2 kg or 41.9% of the initial excess weight. Simultaneously with this loss of weight, there was an improvement in the gynecological symptoms in all three groups. These symptoms included those seen in the premenstrual phase (sexually active age group) and menopause-related symptoms in the perimenopausal and post menopausal groups. The acceptability and safety of Isomeride were also confirmed in this study. PMID- 1631480 TI - Sweets and other sugary products tend to be the primary etiologic factors in dental caries. AB - The aim of this study was to analyze the relationships between caries incidence and each of seven caries-related factors in a group of 15- to 18-yr-olds as well as in single and combined subgroups representing favorable or less favorable fractions of six of the factors. Sixty-nine 18-yr-olds were interviewed about consumption of sweets and other sugar-containing products during the past 3 yr and examined for oral hygiene, salivary counts of mutants streptococci and lactobacilli, salivary flow rate and oral sugar clearance time at the ages of 15 and 18. Simple linear correlations and a stepwise multiple regression analysis were used to compare ranks and explanatory values. The highest correlations were obtained for intake of sweets and intake of other sugary products, with r values increasing from 0.25 and 0.16, respectively, in the total material to 0.70 and 0.67 in less favorable fractions of oral hygiene, salivary flow rate and other sugary products in the former case, sweets in the latter. The stepwise multiple regression analysis revealed that sweets and other sugary products contributed 12 percentage points to the total explanatory value, which was as low as 19%. PMID- 1631481 TI - Caries associated microflora in plaque from orthodontic appliances retained with glass ionomer cement. AB - The caries associated microflora in dental plaque adjacent to orthodontic brackets retained with a glass ionomer cement (GIC) and a resin based composite was investigated using the split-mouth technique. 3, 8, and 28 days after the onset of the appliances, 48-h-old plaque was sampled. An increasing prevalence of mutans streptococci and lactobacilli in plaque from both retaining materials was found. A tendency to colonize more frequently around the composite retained brackets was noticed for both types of bacteria. The proportion of mutans streptococci in relation to the total viable count was significantly higher in plaque samples from composite retained brackets compared to GIC retained 1 month after onset of treatment. The results suggest that a less caries inducing microflora may develop when GIC is used as luting agent in orthodontic dentistry. PMID- 1631482 TI - Diagnosis of dentin involvement in occlusal caries based on visual and radiographic examination of the teeth. AB - The purpose of the present study was to examine the validity of visual, radiographic and combined visual-radiographic examination of occlusal caries, with special reference to the diagnosis of dentin lesions, using the microscopic diagnosis after sectioning the teeth as validating criterion. Thirty extracted permanent molar teeth with signs of occlusal caries were selected and radiographed using a standard method similar to bitewing. Ten dentists, five from the Department of Cariology and Endodontics and five from the Department of Pedodontics, were asked to make a visual, radiographic and combined visual radiographic caries examination with an interval of at least 1 month between different examinations. The teeth were sectioned bucco-lingually and the caries assessed as enamel or dentin lesion in a stereomicroscope. The sensitivity/specificity of the diagnoses of dentin lesions was 0.72/0.41 for the visual, 0.66/0.50 for the radiographic, and 0.86/0.64 for the combined visual radiographic examinations. The Receiver Operating Characteristic (ROC) method revealed a statistically significant difference between combined visual radiographic examination and the two other, but not between the isolated visual or radiographic examination. It is concluded that the combined use of visual and radiographic examination is better than either visual or radiographic examination alone. PMID- 1631483 TI - Influence of transient salivary flora on assessment of mutans streptococci level by the "Strip mutans" method. AB - The Dentocult SM ("Strip mutans") method occasionally shows decoloration of broth and of colonies of mutans streptococci on the plastic strip, thereby making interpretation difficult. In an attempt to explain the phenomenon and to investigate the influence of the salivary flora on the "Strip mutans" method, a total of 46 subjects were sampled. Saliva was analyzed using the "Strip mutans" method and conventional plating techniques to identify mutans streptococci, enterococci, staphylococci, enteric bacteria, and yeasts. Approximately 85% of the "Strip mutans" scores coincided with the conventional MSB-plating method. Two samples showed decolored mutans streptococci colonies on the "Strip mutans" strip. Enterococcus spp. were present in the saliva of these test subjects and could grow in the "Strip mutans" broth. Enterococcus faecalis was able to induce the same type of decoloration under experimental pure culture conditions. Three "Strip mutans" samples showed small colonies of mutans streptococci, visible only under magnification (x 10-20). Staphylococcus epidermidis was present in these saliva samples and showed heavy growth in the broth. Under experimental pure culture conditions S. epidermidis also inhibited the growth of mutans streptococci to some extent. PMID- 1631484 TI - Uptake of KOH-soluble and KOH-insoluble fluoride in sound human enamel after topical application of a fluoride varnish (Duraphat) or a neutral 2% NaF solution in vitro. AB - The uptake of alkali-soluble fluoride (calcium fluoride-like material and adsorbed fluoride) and alkali-insoluble fluoride (apatitically bound fluoride) on sound human enamel from treatment with Duraphat or a neutral 2% NaF solution was investigated in vitro. Blocks from impacted third molars were used. More fluoride was deposited on the enamel from the neutral 2% NaF solution than from the Duraphat treatment. All the fluoride could be dissolved in alkali. Globules of calcium fluoride-like material were demonstrated by scanning electron microscopy. Chemical analysis showed no measurable increase in the apatitically bound fluoride (alkali-insoluble fluoride) after brief exposures. Duraphat-treated samples submerged in water after the exposure lost only about 50% of the deposited fluoride, whereas samples treated with 2% NaF are known to lose all their fluoride under similar circumstances, a condition which may be related to the favorable clinical effect of Duraphat. PMID- 1631485 TI - Efficacy of bone-fill favoring treatment on juvenile periodontitis. AB - In this study we evaluated the effect of bone-fill favoring mechanical treatment on the marginal bone level and periodontal pockets of juvenile periodontitis patients. A total of 10 patients (3 men and 7 women) 13-29 yr of age were treated until no gingivitis or periodontal pockets were present. The intensive therapy (3 8 wk) included scaling, curettage and modified Widman flaps. The maintenance therapy comprised 4 recall visits during the first year after therapy and 2-5 visits per year thereafter. The efficacy of the therapy was evaluated by radiologic measurements of bony defects (%) 12 and 16-65 months after the treatment. The results showed a significant improvement both 1 yr after treatment and at the end of the study. The bone loss was 10.1% less than prior to the treatment and no sites with new bone loss were found after therapy in any of the patients. The bulk of healing took place during the first year after the active therapy, while some further improvement was detected thereafter. Our results show that non-resective mechanical treatment allows excellent healing and regeneration of JP lesions. Our findings also suggest that an adequate follow-up period is needed before definite conclusions can be drawn about the efficacy of the treatment procedures used. PMID- 1631486 TI - Ultrasound image of human masseter muscle related to bite force, electromyography, facial morphology, and occlusal factors. AB - The thickness of the human masseter muscle, corresponding approximately to a cross-section at the most bulky part of the superficial portion, was measured by ultrasound scanning at three sites 1 cm apart. The study included 13 women, 21-28 yr of age, with a minimum of 24 teeth and without craniomandibular disorders. Ultrasonography produced a well-defined depiction of the muscle with distinct tendinous structures. The average thickness at the measuring sites varied from 8.83 to 11.08 mm with the muscle relaxed, and increased significantly during contraction to average values between 9.84 and 12.57 mm. The study showed a connection between measures of masseter thickness and function of the muscle, as well as parameters generally associated with masseter muscle function. Muscle thickness at the voluminous anterior part of the superficial portion was systematically and significantly correlated to bite force, occlusal tooth contact and cephalometric data (anterior face height, vertical jaw relation and mandibular inclination). In conclusion, ultrasound scanning gave an uncomplicated and a reproducible access to parameters of jaw muscle function and its interaction with the craniomandibular system. PMID- 1631487 TI - Improvement of oral hygiene in patients with rheumatoid arthritis. AB - Programs in power toothbrushing, manual toothbrushing with conventional fluoride toothpaste and with a chlorhexidine/fluoride gel has been evaluated for plaque removal in an observer blind cross-over clinical trial on 14 rheumatoid arthritis patients. All three regimens lead to considerable improvement in oral hygiene. The use of an electric toothbrush was slightly more effective than a manual brush. Brushing with a chlorhexidine/fluoride gel gave the best results, but its clinical use is limited by unacceptable taste, discoloration and possibly adverse soft tissue effects. PMID- 1631488 TI - Effect of procedure on diametral tensile strength of composite resin. AB - The sensitivity of the test for diametral tensile strength to variations in testing procedure was investigated. Composite resin specimens of four different surface roughnesses at both ends of the specimens were loaded at one of three crosshead speeds. The diametral tensile strength values varied between 43.9 and 65.7 MPa. Diametral tensile strength was found to decrease with increasing loading rate, with decreasing roughness of the specimens, and with increasing length of the cylindrical specimens. The significant influence of the surface roughness is suggested to be a result of the correlation between roughness and length of specimens, and not the expression of a true influence on diametral tensile strength of surface roughness of the specimens' ends. PMID- 1631489 TI - Bond strength of porcelain on cast vs. wrought titanium. AB - The bond strength of porcelain fused to cast and wrought titanium surfaces was calculated from fracture loads in a 4-point bending test. Two different porcelain were applied (O'Hara and Duceratin). The surface of Ti-cast specimens was treated in two different ways to produce variations in the impurity level before porcelain veneering. Microhardness measurements as well as scanning electron microscopy with EDX analysis were conducted. The results showed no significant difference in bond strength between the two porcelains. Nor was any difference in bond capacity found between thoroughly blasted castings and wrought titanium. Significantly lower bond strengths were observed for lightly blasted specimens and for specimens treated with Gold bonding agent. Impurities in the surface region of the castings were found to be due to contact with the investment during solidification. This indicates that a thin surface layer (50-100 microns) of the casting should be removed before firing of the porcelain. PMID- 1631490 TI - The role of resective surgery in the treatment of the carcinoid syndrome. PMID- 1631491 TI - Acid and pepsin secretion in patients with esophagitis refractory to treatment with H2 antagonists. AB - The basis for treatment of esophagitis is suppression of gastric acid secretion. To determine whether lack of healing with standard treatment with H2 antagonists might be due to abnormal gastric secretion, 30 patients who remained unhealed after 12 weeks' therapy with histamine H2 antagonists were compared with 20 patients who healed after 6 or 12 weeks' therapy. The groups were matched with regard to age, weight, sex, and presence of hiatal hernia or duodenal ulcer. There were no significant differences in fasting gastric juice volume, pH, or acid or pepsin concentrations. All 30 refractory patients had basal acid output (BAO) less than 10 meq/h, and 16 of 30 had BAO less than 2 meq/h--that is, there was no evidence of hypersecretion in any refractory patients. Moreover, basal and maximal acid and pepsin outputs were not higher in non-healing patients. Refractory patients had a higher prevalence of initial severe (grade 3 or 4) esophagitis (80% versus 35% in those who healed, p less than 0.01) and of strictures (73 versus 15%, p less than 0.001), both of which serve as markers for refractoriness to treatment. Thus 77% of patients who presented with severe esophagitis failed to heal versus 32% of those with mild or moderate esophagitis (p less than 0.01). Refractoriness of esophagitis is not related to gastric acid or pepsin hypersecretion but represents a constitutional susceptibility to esophagitis and requires both short- and long-term treatment strategies that are not yet well defined. PMID- 1631492 TI - Quantification of lipopolysaccharides in human bile with or without gram-negative bacteria. AB - Lipopolysaccharide (LPS) was assayed in 78 samples of human common-duct bile, obtained at endoscopic retrograde cholangiography. The LPS was assayed by a chromogenic limulus amebocyte lysate (LAL) test, after dilution of bile samples in heparinized plasma and inactivation of inhibitors. The assay was not influenced by other biliary constituents, as demonstrated by the recovery of standards. Bile pigments did not influence the results. The LAL test was positive in 60 of the samples, 59 of which had a positive culture for gram-negative bacteria or Candida sp. The levels of LPS were significantly correlated to the total number of bacteria (n = 16, R = 0.55, p less than 0.05). The median LPS level was 35,250 ng/l and showed a very large variation (140 ng/l to 27.8 mg/l). In four of the samples gram-negative bacteria were present, but no LPS could be detected. The study demonstrates the presence of LPS in great quantities in human bile and supports the feasibility of using the LAL test on bile samples. The presence of LPS (within the detection limit) appears to be associated with local microbial colonization. PMID- 1631493 TI - Evaluation of ketogenesis in seriously reduced hepatic mitochondrial redox state. An analysis of survivors and non-survivors in critically ill hepatectomized patients. AB - Ketogenesis was evaluated in 33 critically ill hepatectomized patients in relation to the arterial ketone body ratio (acetoacetate to 3-hydroxybutyrate), which reflects hepatic mitochondrial redox state. In 15 patients whose arterial ketone body ratio decreased to below 0.4, blood ketone body levels were significantly increased concomitant with marked increase of blood lactate and plasma alanine levels. In the 6 survivors of these 15 patients, the arterial ketone body ratio was restored within the next 2 days, and blood ketone body levels were decreased. By contrast, in the nine non-survivors, the arterial ketone body ratio remained below 0.4, and blood ketone body levels were decreased, accompanied by significant increases in blood lactate and plasma alanine levels in the terminal stages. These results suggest that ketogenesis acts as an alternative process for ATP synthesis in the liver in critically ill patients. Death occurs when the liver falls into an energy crisis concomitant with the cessation of ketogenesis. PMID- 1631494 TI - Functional aspects of small-bowel transplantation in rats. AB - Although clinical small-bowel transplantation is still severely hindered by rejection of the graft, prolonged graft survival can be achieved by using cyclosporin A in several experimental models of small-bowel transplantation. In an immunologically quiescent phase after transplantation, the important question arises whether a small-bowel allograft has enough functional capacity to maintain a normal nutritional status. We investigated the functional capacity of orthotopic small-bowel transplants and evaluated the ability of the total small bowel transplant to absorb orally given cyclosporin in the early postoperative period and the effect of this oral cyclosporin treatment on allograft survival as compared with intramuscular administration. Between 3 and 7 months postoperatively, recipients of syngeneic and allogeneic total small-bowel transplants and syngeneic jejunal segmental grafts had significantly decreased serum triglyceride levels. Total serum protein and albumin concentrations, serum cholesterol values, fecal fat excretion, and percentage of split fatty acids were normal. One year after transplantation the weight in the groups transplanted with a total small-bowel graft was not different from age-matched untreated controls. Animals grafted with a segmental graft, however, showed a significantly impaired growth and had not reached a normal weight 1 year after transplantation. Growth was also significantly impaired after near-total small-bowel resection. These animals had to be killed because of their poor condition. Cyclosporin absorption after small-bowel transplantation equalled that in normal controls. Graft survival after intramuscular treatment, however, was significantly better than after oral treatment. PMID- 1631495 TI - Binding of epidermal growth factor to receptors in preparations of enriched porcine parietal cells and inhibition of aminopyrine uptake. AB - Preparations of isolated porcine gastric cells, enriched in parietal cells, were used to study binding of epidermal growth factor (EGF) to receptors and subsequent inhibition of [14C]aminopyrine uptake. EGF in concentrations from 10( 10) to 10(-7) M inhibited aminopyrine uptake stimulated by 10(-5) M histamine with an IC50 of 3 x 10(-10) M. [125]EGF bound in a saturable and specific manner to sites on cells in preparations containing 40-90% parietal cells. Mean apparent dissociation constant for the sites was 1.6 x 10(-9) M, with an average number of approximately 20,000 sites per cell. Endocytosis of ligand by parietal cells was limited, amounting to 10-20% of bound EGF after 1 h of incubation at 37 degrees C. Occupation of a fraction of the receptors caused a maximal reduction by 40% of aminopyrine uptake in histamine-stimulated cells, suggesting the occurrence of spare receptors. The results indicate the existence of specific receptors for EGF on porcine parietal cells exerting a regulatory influence on acid secretion. PMID- 1631496 TI - Changes in splanchnic hemodynamics in inflammatory bowel disease. Non-invasive assessment by Doppler ultrasound flowmetry. AB - An increase in splanchnic blood flow in both arterial and venous beds has been demonstrated in inflammatory bowel disease (IBD) by means of angiographic and scintigraphic studies. Doppler ultrasound (US) enables a non-invasive evaluation of splanchnic arterial inflow in the superior mesenteric artery (SMA) and of venous outflow in the portal vein. The aim of this study was to assess the role of Doppler US in detecting changes in the hemodynamic variables measured in patients with IBD. Forty-five patients with IBD were studied, including 22 with Crohn's disease (CD) and 23 with ulcerative colitis (UC), and compared with 45 matched normal subjects. The mean velocity of portal flow (Vmean) and the resistance index (RI) of the SMA were evaluated by Doppler US. In CD the Vmean of portal flow was significantly higher in patients with active disease than in controls (p less than 0.001) and patients with inactive disease (p less than 0.001). The RI of the SMA was significantly lower in active disease than in controls (p less than 0.005), but no significant difference was noted between active and inactive CD. Also in UC, the Vmean of portal flow was significantly higher in patients with active disease than in controls (p less than 0.01) and patients with inactive disease (p less than 0.05). The RI of the SMA was significantly lower in active disease than in controls (p less than 0.005) and in patients with inactive disease (p less than 0.005). Doppler follow-up studies were carried out in 10 patients after initiation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1631497 TI - Has smoking changed the epidemiology of ulcerative colitis? AB - The influence of smoking on the risk of developing ulcerative colitis is well documented. Compared with lifetime non-smokers, the risk is reduced in smokers and increased in ex-smokers. During the past 50 years general smoking habits have changed considerably. The proportions of smokers and ex-smokers among men and women have undergone significant changes and, consequently, probably also their risk of ulcerative colitis. A review of 56 earlier epidemiologic studies of ulcerative colitis from 1930 to 1990 showed that the sex distribution in ulcerative colitis has changed from an earlier female predominance that has now been replaced by a male predominance. In contemporary pediatric studies no such changes were seen. We propose that these changes in adults are not related to the disease per se but to an extrinsic factor affecting adults but not children- namely smoking. PMID- 1631499 TI - Omeprazole does not cause unscheduled DNA synthesis in rabbit parietal cells in vitro. AB - Parietal cells from rabbit gastric mucosa, enriched to greater than 90% purity, were used to study the effect of the H+,K(+)-ATPase inhibitor omeprazole on DNA in vitro. In this preparation, omeprazole undergoes acid-catalyzed conversion to its active form, the sulfenamide, which subsequently binds to luminal SH groups of the H+,K(+)-ATPase and thereby inhibits acid secretion. In the parietal cell fraction the S-phase inhibitor hydroxyurea (HU) decreased [3H]thymidine uptake by 40% as measured by liquid scintillation counting (LSC), presumably due to inhibition of scheduled DNA synthesis in contaminating stem cells. In the presence of HU, irradiation with ultraviolet light (UV) or treatment with the gastric carcinogen, 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) increased [3H]thymidine uptake by a factor of 5. Autoradiography of isolated, stimulated parietal cells showed that UV irradiation and MNNG treatment increased the average number of silver grains over the nuclei 18-fold and 4-fold, respectively. In contrast, treatment of histamine-stimulated parietal cells with omeprazole or ranitidine in concentrations 100 times the IC50 value for inhibition of acid secretion in the parietal cells did not increase [3H]thymidine incorporation above the control levels, measured either by LSC or by autoradiography. Extracted DNA from stimulated parietal cells treated with [3H]omeprazole or [3H]MNNG showed no binding of [3H]omeprazole but considerable binding of [3H]MNNG. It is concluded that parietal cells can undergo DNA repair, but there is no indication that omeprazole, or its acid-derived metabolites, should cause any damage to DNA, nor does it bind to DNA in its target cell, where the highest concentrations of omeprazole and its acid-derived products are found. PMID- 1631498 TI - Significance of serum type-IV collagen levels in various liver diseases. Measurement with a one-step sandwich enzyme immunoassay using monoclonal antibodies with specificity for pepsin-solubilized type-IV collagen. AB - Serum type-IV collagen levels determined with a one-step sandwich enzyme immunoassay (EIA) using monoclonal antibodies with specificity for pepsin solubilized type-IV collagen were compared with histologic changes in liver biopsy specimens from 107 patients with various liver diseases. Serum type-IV collagen levels were increased in the groups with liver diseases compared with controls. The serum type-IV collagen levels in the group with alcoholic cirrhosis showed significantly higher values than the other groups (P less than 0.05). A significant positive correlation was found between the serum type-IV collagen level and the degree of fibrosis or cell infiltration in 107 patients. Immunolocalization of type-IV collagen was observed around blood vessels and bile ducts increased in number in the portal tracts, with cell infiltration and fibrosis, increased around vessels in fibrous septa, and sinusoidal walls of areas with cell infiltration or necrosis in hepatic lobules, and along the boundary between fibrous septa and hepatocytes. The present data indicate that serum type-IV collagen may be a sensitive marker for active fibrosis and that the elevation of serum type-IV collagen level primarily reflects the enhancement of type-IV collagen synthesis and deposition in the liver tissue at the stage of active fibrosis in liver disease. PMID- 1631500 TI - Epidemiology of nephritis. Review. PMID- 1631501 TI - Effect of orchidectomy on serum concentrations of testosterone and dihydrotestosterone in patients with prostatic cancer. AB - Because it is well known that prostatic cancer is dependent on testosterone, and that dihydrotestosterone is the active mediator of the androgen action in the prostatic cell, we studied serum concentrations of testosterone and dihydrotestosterone in 84 patients with prostatic cancer, 40 of whom were treated by orchidectomy, and 44 who were not treated. There was a significant correlation between testosterone and dihydrotestosterone concentrations in the untreated group, but no correlation among the patients treated by orchidectomy. The results indicate that the effectiveness of orchidectomy as androgen withdrawal treatment in prostatic cancer should be assessed by measurement of both dihydrotestosterone and testosterone concentrations. PMID- 1631502 TI - Transrectal ultrasonography in the staging of localized prostatic carcinoma. A pilot study. AB - Transrectal ultrasonography (TRUS) was evaluated as a staging procedure in ten patients with localized prostatic carcinoma. The ultrasound images were correlated to histopathological whole-mount step sections of the surgical specimens after radical prostatectomy. Nine of the patients had pathological stage T3 (pT3) and only one was pT2. TRUS gave a diagnostic accuracy of 60% compared to 10% both for digital rectal examination (DRE) and computer tomography (CT) in detecting extracapsular tumor spread. We conclude so far that TRUS is superior to DRE and CT in detecting extracapsular tumor spread. Further we state that whole-mount step section of the surgical specimens is mandatory in order to achieve a correct pathological staging (pT-stage). PMID- 1631503 TI - Adenocarcinoma of the prostate and metastatic medullary compression. A retrospective study of 22 patients. AB - A retrospective study of 709 patients with prostatic cancer was carried out. Twenty-two developed medullary cord compression (an incidence of 3%). All but two of the 22 patients were treated by radiation and 10 had additional hormonal treatment. Ten had some benefit from the treatment, but only 2 of 19 regained their ability to walk. The need for immediate diagnosis and treatment is stressed. PMID- 1631504 TI - Significance of the antireflux valve for upper urinary tract pressure. An experimental study in patients with urinary diversion via a continent ileal reservoir. AB - When bladder substitution is required, a low pressure receptacle and an antireflux valve with low resistance to flow is essential for preservation of the upper urinary tract. The aim of this study was to evaluate whether these criteria are attained in the continent ileal reservoir used for urinary diversion. The investigations were performed in six patients more than one year after supravesical urinary diversion via a continent ileal reservoir. The pressure was recorded simultaneously both in the afferent loop and in the reservoir during filling of the reservoir. There was a slow parallel increase in the basal pressure in the reservoir and the afferent loop. Pressure waves appeared sometimes simultaneously and sometimes in only one compartment at a time. Only during short periods of time did the pressure exceed 25 cm of water. The frequency of pressure waves increased with increased filling of the reservoir. The "total pressure" was larger in the reservoir than in the afferent loop. It is the antireflux valve which prevents pressure rises in the reservoir from being conveyed to the upper urinary tract. The resistance to urinary flow was moderate. PMID- 1631505 TI - Long-term partial ureteral obstruction and its effects on kidney function. AB - Previously it has been shown that partial ureteral obstruction present in young rats for 12 weeks results in small morphological changes in the kidney as well as slightly decreased kidney function. In the present study the aim was to examine whether rats obstructed for one year had more advanced changes in morphology and kidney function. The first group of animals examined after three weeks of obstruction showed only modest changes in kidney function with a reduced potassium concentration in the urine but no reduction in the glomerular filtration rate. After one year there was a reduction in urine flow as well as in the excretion of both potassium and sodium. Urine osmolality was also reduced. Glomerular filtration rate measured in this group of animals was reduced in the obstructed kidney by about 60% compared to the contralateral one. There were only small changes in the morphology with no loss in parenchymal weight or compensatory hypertrophy, but there was a significant deformation of the papilla and an increase in inflammatory cells in the parenchyma. In conclusion hydronephrosis during a shorter period is not harmful to kidney function but if sustained for an extended time period kidney function will deteriorate. PMID- 1631506 TI - Results of one and two year follow-up in a clinical comparison of extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy in the treatment of renal calculi. AB - The results of 12 and 24 month follow-up of two groups of similar patients with renal and ureteric calculi treated by percutaneous nephrolithotomy (PCN) and related techniques versus first generation, Dornier extracorporeal shock wave lithotripsy (ESWL) alone or in combination with PCN and/or endoscopy indicated few major differences in the side-effects (complications, readmissions, further procedures) of the two approaches to renal stone treatment up to two years from treatment. However, PCN patients exhibited consistently higher rates of stone clearance whether this was measured cross-sectionally or cumulatively. The higher prevalence of retained fragments in the ESWL group indicates the importance of long-term monitoring of both groups to discover whether there are any significant differences in stone growth and retreatment rates associated with the observed difference in stone-free rates. PMID- 1631507 TI - Serum concentrations of calcitriol and PTH in hemo-dialysis patients on treatment with calcium carbonate. AB - The effects of calcium carbonate and aluminium hydroxide as phosphate binders were investigated in nine patients on chronic hemodialysis. Aluminium hydroxide, 1 g X 3, was given during four weeks followed by a period of four weeks without any phosphate binders and after this calcium carbonate, 2.5 g X 3, was introduced for four weeks. Calcium carbonate resulted in lowering of bioactive PTH in serum from 22.4 to 16.4 pM and a rise of serum calcitriol from 8.0 to 11.5 pg/ml with maintained control of phosphate and without significant difference in the calcium phosphate product. Calcium in serum rose from 2.27 to 2.57 mM and mild hypercalcemia (less than 3.0 mM) in five of the patients could be controlled by dose reduction of calcium carbonate without losing control of serum phosphate levels. We conclude that calcium carbonate offers advantages as a phosphate binder compared to aluminium hydroxide in that it offers equal control of serum phosphate and elevates serum calcium which helps to control the hyperparathyroidism secondary to uremia. PMID- 1631508 TI - Parathyroid function in relation to intestinal function and renal calcium reabsorption in patients with nephrolithiasis. AB - Recently a technique to measure intact parathyroid hormone (PTH), i.e. the biologically active hormone, has been available. The aim of the present study was to apply this method to evaluate the parathyroid function in a material of recurrent renal stone formers (n = 324). Intact PTH was found to be inversely related to both urinary calcium (r = -0.15; p less than 0.01) and serum calcium (p less than 0.02) indicating that in the majority of the patients with hypercalciuria this was accounted for by intestinal hyperabsorption and not by high serum PTH. Hyperabsorption was also the likely explanation for the finding of a positive relationship between the urinary calcium and oxalate excretions (r = 0.22; p less than 0.001) in medication-free patients without intestinal disorders, i.e. without enteric hyperoxaluria. Altogether 25 patients (7%) had elevated serum PTH concentrations. They were followed up with fasting serum and urinary electrolytes and an oral calcium loading test (1 g of calcium) in order to evaluate the importance of renal and intestinal factors responsible for the elevated serum PTH concentrations. The investigation was carried out on a free diet and on low and high calcium intakes, respectively. The incidence of intestinal malfunction, which was sometimes present without clinical symptoms, was found to be approximately the same as that of impaired renal conservation of calcium. The findings in the patients with intestinal malfunction were a reduced intestinal absorption of calcium and an enhanced tubular reabsorption of calcium (TRCa), with greater reabsorption of calcium for higher PTH values. In patients with impaired renal conservation of calcium despite the raised PTH there was no correlation between PTH and TRCa. When PTH was suppressed during the oral calcium load the TRCa was found to be inappropriately low and the renal defect obvious. The intestinal calcium absorption was secondarily increased to compensate for the renal losses. PMID- 1631509 TI - Effect of treatment of anaemia with erythropoietin on neuromuscular function in patients on long term haemodialysis. AB - To study the effect of treatment of anaemia with recombinant human erythropoietin (r-HUEPO) on neuromuscular function in patients undergoing haemodialysis for chronic renal failure, six patients were given r-HUEPO in an initial dose of 50 u/kg three times a week and their haemoglobin concentration was measured. The dose was increased by 25 u/kg every four weeks if the response was not satisfactory. In five patients anaemia had been corrected within 12 weeks of initiation of treatment. Neuromuscular function was evaluated before treatment, half way through, and after correction of anaemia by clinical examination and neurophysiological studies including motor nerve conduction velocity, distal latency, electromyography and test for neuromuscular fatigue. After correction of anaemia there was a significant increase in motor nerve conduction velocity, a decrease in the duration of motor unit action potential, and a lessening of neuromuscular fatigue. We conclude that treatment of anaemia with r-HUEPO in patients with chronic renal failure undergoing haemodialysis may improve neuromuscular function. PMID- 1631510 TI - Epidermoid cysts of testis. AB - A 27-year-old man presented with bilateral testicular pain and enlargement of the right testis caused by a cystic mass. Histological examination of a frozen section at exploration excluded malignancy and the final diagnosis after local excision was benign epidermoid cyst. The patient remained well three years later. PMID- 1631511 TI - Large cell calcifying Sertoli cell tumor of the testis. AB - We report on a patient with a large cell calcifying Sertoli cell tumor of the testis and review the literature of this recently described rare subtype of Sertoli cell tumor. Twenty-one cases, including ours, have been reported in the literature. Six of twenty cases (28%) had clinically evident endocrine abnormalities and eight of twenty-one cases (38%) were bilateral. This tumor has a low malignant potential with only one patient known to have metastatic disease. PMID- 1631512 TI - Distal ureteral atresia associated with ipsilateral renal dysplasia. AB - A 56-year-old man presented with unilateral ureteral atresia associated with renal dysplasia. He had no previous urinary symptoms. The diagnosis was established histopathologically after nephroureterectomy. PMID- 1631513 TI - An unusual cause of acute abdomen. PMID- 1631514 TI - Benign retroperitoneal schwannoma. AB - A rare case of benign retroperitoneal schwannoma in a 76-year-old man is reported. Ultrasound and computerized tomography disclosed two cystic retroperitoneal tumors sized 12 cm and 7 cm. The larger tumor was located anterior to psoas muscle and the smaller one was within the muscle. The larger tumor was excised via laparotomy. After 3.5 years follow-up the intramuscular tumor has remained unchanged and the patient has no symptoms. PMID- 1631515 TI - Epistaxis in renal carcinoma. AB - A 62-year-old man presented with recurrent epistaxis and a mass in the left nostril. Histological examination of the excised tissue showed clear cell carcinoma and he was found to have an asymptomatic carcinoma of the right kidney. A year after right nephrectomy, excision of the left maxilla, and radiotherapy he was well with no sign of recurrence. Early recognition of this rare condition and excision of both primary and metastatic tumours are recommended. PMID- 1631516 TI - [Clinical presentation of tuberculosis among immigrants seen at the antituberculosis outpatient clinic in Lausanne]. AB - Between 1987 and 1990, 162 new immigrants entering Switzerland were treated for tuberculosis at the TB Dispensary, Lausanne. Fifty-three were smear or culture positive. In 93% of the cases, the diagnosis was suspected at a screening examination for TB shortly after arrival in Switzerland. The diagnosis of TB was established on the basis of radiological abnormalities and the results of bacteriology and the clinical and/or radiological course under treatment. The prevalence of TB was 174.3 cases per 100,000 among foreign workers and 1357.5 per 100,000 among refugees in the group of immigrants entering the Canton of Vaud. Symptoms related to TB were mentioned by 18% of patients, clinical abnormalities were noted in 7.4%. The tuberculin test was positive (greater than 10 mm) in 94% of patients. Thirty patients, including six smear or culture positive cases, were lost to follow-up or stopped treatment before the scheduled end. A policy of active screening for TB among new immigrants allows detection at an early stage and, in combination with proper treatment, should prevent extension of the disease within groups of immigrants. PMID- 1631517 TI - [Colonoscopic endosonography in the diagnosis and follow-up care of colorectal tumors]. AB - We studied the usefulness and accuracy of a flexible endoscopic ultrasound system (EUS) in preoperative staging of tumor invasion and involvement of lymph nodes of rectal tumors. Comparison of preoperative EUS findings with histopathologic TNM classification (UICC 1987) was possible in 12 patients. The depth of tumor invasion was correctly staged in 9/12 patients (75%), and lymph node staging was correctly predicted in 9/12 patients (75%). Our results indicate that flexible coloscopic ultrasonography is as accurate as rigid systems for staging of colorectal cancer. It will become a sensitive method for early diagnosis of local recurrence. The flexible endoscopes are well tolerated by patients and more proximal lesions which cannot be reached with the rigid instruments can also be examined. PMID- 1631518 TI - [Exercise and cancer. An epidemiologic short review of the effects of physical activity on carcinoma risk]. AB - It is only during the past decade that occupational and leisure-time physical activity--whose importance for the prevention of cardiovascular diseases is well documented--has become a focus of research in cancer epidemiology. The most consistent observation of more than 15 epidemiological studies published in the 1980s is an average increase in the risk of colon cancer of 75 to 80% for physically inactive men and women, as compared to their more active counterparts. No study at all found a direct relationship between physical activity and colon cancer risk. A hypothetical explanation for this likely but unproven protective effect of regular exercise against colon cancer is that physical activity stimulates colon peristalsis, hereby reducing enteral transit time and diminishing exposure of the intestinal mucosa to fecal carcinogens. The epidemiologic evidence for a protective effect of exercise against rectal cancer and other cancers, however, is not sufficient. Isolated observations of a direct relationship between physical activity and the risk of cancer (e.g. prostate) have even been reported. For women, there is preliminary evidence of a protective effect of athletic activity against cancers of the breast and the reproductive system for which hormonal factors may be responsible. The cancer-protective effect of exercise per se is apparently too modest to serve as a justification for a general recommendation to take regular exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1631520 TI - [Continuing education: theory and practice in close union]. PMID- 1631519 TI - [Systemic Nocardia infection in an AIDS patient]. AB - We report the case of a patient with Aids, Kaposi's sarcoma and a systemic nocardial infection. After surgical drainage and adequate antibiotic treatment the infection was cured. Under secondary antimicrobial prophylaxis no relapse has occurred to date. Generalized N. asteroides infections have been rarely described in patients with Aids and the possible reasons for this are discussed. PMID- 1631521 TI - [Do new diagnostic tests improve the differential diagnosis and therapy of periodontitis? A review]. AB - New diagnostic tools give access to information that was previously not available by classical clinical means. This includes methods for the determination of the composition of the microbial flora or for monitoring specific reactions of host tissues to the accumulation of plaque. DNA-probes, monoclonal antibodies and enzyme assays have already been advertised and are sold to dentists. The practical value of new tests depends upon the possibility to improve the efficacy of treatment based on previously inaccessible information. This paper reviews frequently raised clinical questions, the possible answers coming from new diagnostica, and the potential impact of this knowledge on periodontal therapy. PMID- 1631522 TI - Effect of metronidazole on experimental periodontitis: cell population characteristics. AB - Systemic administration of metronidazole during an experimental periodontitis resulted in significantly less active tissue destruction compared to drug-free animals. However, the size of the inflammatory infiltrates in both groups was similar. The present study assessed cell populations within the infiltrates of metronidazole receiving and drug-free animals. In the experimental group, metronidazole was administered orally to 4 squirrel monkeys (100 mg/kg body weight per day) for 17 days. After 3 days, marginal periodontitis was induced around maxillary and mandibular bicuspids and molars by tying silk ligatures at the gingival margins. In 4 monkeys of the drug-free control group, periodontitis was induced around similar teeth. Biopsies of the gingiva representing 3, 7 and 14 days of experimental periodontitis were taken in both groups. The total number of cells and the number of polymorphonuclear leucocytes (PMN's) were counted on one-micron sections. At 3 days after ligature placement, there were numerically less total cells and PMN's in the metronidazole receiving experimental group. At 7 and 14 days the total number of cells and the number of PMN's was significantly greater in the drug-free control group, where more active periodontal breakdown had occurred. These results emphasize the potentially destructive role of PMN's in acute bursts of tissue destruction. PMID- 1631523 TI - [The addition of potassium rhodanide to artificial saliva in electrochemical corrosion research]. AB - Polarization curves of five dental alloys and pure platinum were made in artificial saliva with and without potassium-thiocyanate. From 400 mV (SCE) the noble alloys show a current rise. The reason for this current rise not corrosion, but a redox reaction of the potassium-thiocyanate. For potentiodynamic polarization measurements the addition of potassium-thiocyanate to the artificial saliva is problematic. PMID- 1631524 TI - [Ceramic veneer shells. The use of ceramic veneer shells is presented via a clinical case]. PMID- 1631525 TI - [Anterior tooth trauma. The preservation and treatment of the injured tooth]. PMID- 1631526 TI - Biodegradation of aquatic organic matter with reference to drinking water treatment. AB - This paper presents results obtained in a pilot scale investigation of biological treatment for preparation of drinking water from the North Saskatchewan River at Edmonton, Canada. Although the concentration of natural organic matter (NOM) in the raw water varied substantially over the study period, parameters measuring the biodegradability and reactivity to chlorine of the NOM were closely correlated to the NOM concentration. As a result of treatment including ozonation and adsorption, two patterns of response emerged. Some parameters decreased through each step of the treatment process while others usually increased following ozonation and then decreased through subsequent steps. The levels of this latter group were decreased by biological activity in the filters (except for one treatment stream) and further reduced in the biologically active granular activated carbon (GAC) contactors. PMID- 1631527 TI - Quality of air in industrial cities of the USSR and child health. AB - In cities containing different industries, studies of the health status of children demonstrate a correlation between geographic structure and pollution. Variations and changes in the demographic and reproductive status of a population, total morbidity and morbidity of the respiratory tract has been determined. A classification of cities with different levels of atmospheric pollution has been performed. PMID- 1631528 TI - Study of environmental pollutants in and around the city of Lahore, Pakistan. II. Concentrations of cadmium in blood of different groups of people. AB - Cadmium concentrations were measured in the whole blood of six different groups of persons living in and around the city of Lahore. The cadmium concentrations in the blood of normal persons of both sexes were distributed log normally. The values were lower among the young and increased gradually to reach a plateau at an average age of 45 years and then decreased. There was a trend of a gradual increase of cadmium blood concentrations with age in male industrial workers and female exposed groups. Cadmium-blood concentrations in cancer patients were significantly lower when compared to the rest of the groups, however no statistical correlation between Cd-blood concentration and age of cancer patients was observed. PMID- 1631529 TI - Distribution of heavy metals in Elcho Island, Northern Territory, Australia. AB - The concentration of four metals in waters and seven metals in oysters, clams and sediments from Elcho Island, Northern Territory, were determined during the dry season of 1987. The measured concentration of cadmium, zinc, copper and lead in unfiltered water were: cadmium, 0.02-0.27; zinc, 0.09-3.70; copper, 0.60-4.78; lead, 0.12-2.39 micrograms l-1, and iron, cadmium, zinc, manganese, copper, nickel and lead in oysters, 13.07-273.55, 0.29-10.63, 2.39-8.51, 0.25-4.84, 0.45 8.76, 0.16-0.59, 2.59-9.38 micrograms g-1 wet weight, and in clam, 94.84-419, 6.0 20.3, 1.09-6.28, 2515-6256, 0.47-3.18, 1.71-5.64, 0.45-2.17 micrograms g-1 wet weight, and in sediments, 3219.1-10871.1, 1.36-2.68, 2.7-6.55, 19.4-105.7, 0.65 1.91, 4.16-21.8 and 5.66-23.9 micrograms g-1 dry weight. Accumulation of manganese in razor clam was highest in spite of low concentration in the surrounding sediment, therefore it could be used as a bioindicator of manganese in a tropical environment. The level of cadmium and lead exceeded the National Health and Medical Research Council (NHMRC) recommended limit. In general, level of other metals were lower as compared to the concentration of these metals in Darwin Harbour. PMID- 1631530 TI - Sources of present Chernobyl-derived caesium concentrations in surface air and deposition samples. AB - The sources of Chernobyl-derived caesium concentrations in air and deposition samples collected from mid-1986 to the end of 1990 at Munich-Neuherberg, Germany, were investigated. Local resuspension has been found to be the main source. By comparison with deposition data from other locations it is estimated that within a range from 20 Bq m-2 to 60 kBq m-2 of initially deposited 137Cs activity approximately 2% is re-deposited by the process of local resuspension in Austria, Germany, Japan and the United Kingdom, while significantly higher total resuspension is to be expected for Denmark and Finland. Stratospheric contribution to the present concentrations is shown to be negligible. This is confirmed by cross correlation analysis between the time series of 137Cs in air and precipitation before and after the Chernobyl accident and the respective time series of cosmogenic 7Be, which is an indicator of stratospheric input. Seasonal variations of caesium concentrations with maxima in the winter months were observed. PMID- 1631531 TI - Evaluation of heavy metal pollution in the Venetian lagoon by using Mytilus galloprovincialis as biological indicator. AB - This study reports the analysis of heavy metal (Cd, Co, Cu, Cr, Hg, Fe, Mn, Ni, Pb, Zn) and As accumulated in the mollusc Mytilus galloprovincialis collected in the Venetian lagoon between March and September 1988. This environmental biomonitoring project was carried out using natural population of the molluscs attached to the 'Briccole', which limit the navigation canals into the lagoon. These data were compared with those reported by other authors in analogous studies published about a decade ago. A small improvement on the heavy metal pollution of the Venetian lagoon can be deduced from this comparison, presumably depicting a positive signal of a new downward trend in metal concentrations. Continuous monitoring of the fragile lagoonal ecosystem must be an important commitment due to the economic and historical importance of the Venetian lagoon. PMID- 1631532 TI - Reduced dietary cadmium intake in past 12 years in a rural area in Japan. AB - To examine possible reduction in dietary cadmium (Cd) intake, 24-h duplicates of diet were collected twice in the same village in north-eastern Japan, once in 1976-1977 (71 samples) and then in 1989 (198 samples) and analyzed for Cd contents. The statistical analysis by sex and age decade showed that there has been a significant (P less than 0.01-0.05, depending on sex and age) reduction in Cd intake during this 12-year period. The intake by men at 30-59 years was 28.8 micrograms/day (as a geometric mean of 41 samples) in 1976-1977 and 20.8 micrograms/day in 1989, indicating some 28% reduction, whereas the value for women of the same age range was 24.9 micrograms/day in 1976-1977 and 15.7 micrograms/day in 1989, with a reduction by 37%. A similar reduction in Cd contents was observed in cooked rice samples collected in 1980 and 1990 in the vicinity of the study field. Probable reasons for the improvement are discussed. PMID- 1631533 TI - Lead levels in settled dusts of Tripoli, Libya. AB - The levels of lead in settled dust samples collected near small streets, playgrounds, gas stations and main streets in the Tripoli area have been determined by atomic absorption spectrophotometry. The overall mean values observed were 417, 533, 553 and 797 micrograms g-1 dry wt for the above locations respectively. The overall mean concentration for main streets was significantly higher (P less than 0.05) than for other sites. The data were also compared with those reported in the literature for other cities. PMID- 1631534 TI - Heavy metals and selenium in stranded dolphins of the northern Tyrrhenian (NW Mediterranean). AB - Heavy metal (Hg, Cd, Pb and Zn) and selenium levels were determined in striped (Stenella coeruleoalba) and bottle-nosed dolphins (Tursiops truncatus) stranded along the coast of Tuscany and Latium, Italy in the period 1987-1989. Lead and zinc concentrations were quite low and there was modest accumulation of cadmium in the kidney of both species. Mercury levels were very high, especially in the liver where they reached peaks of 4400 ppm (dry weight) in the striped dolphin and 13,150 ppm (dry weight) in the bottle-nosed dolphin. Selenium levels were also high and were significantly correlated with mercury levels in some organs and tissues. The toxicological significance of the selenium-mercury interaction is discussed. PMID- 1631536 TI - Chirality and drug development. PMID- 1631535 TI - Organic chemicals entering agricultural soils in sewage sludges: screening for their potential to transfer to crop plants and livestock. AB - This paper presents a review and assessment of the pathways and transfers of organic contaminants applied to agricultural soils in sewage sludge. The purpose of the assessment has been to develop a simple screening approach to highlight different chemical fates of organic chemicals in soil and their potential transfers from soil to groundwaters, crop plants and grazing livestock using data on the physico-chemical properties of the compounds of interest. The fate of 46 compounds known to be present in sewage sludges are compared to illustrate the applicability of the procedure. Compounds are screened for their potential to adsorb, volatilise, degrade and leach in soils and to be transferred to plants via retention by root surfaces, root uptake and translocation and foliar uptake and to transfer to animal tissues via soil and herbage ingestion. Recommendations for experimental and field studies are made. It is envisaged that this screening approach can be applied to other chemicals and that it will focus research and aid risk assessments of organic compounds in sewage sludge following land application. PMID- 1631537 TI - Thrombin and its inhibitors. PMID- 1631538 TI - Oct-3 and mammalian development: correction of discussion. AB - The title of the 5 June report on page 1445 by R. C. deL. Milton et al. should have been "Total chemical synthesis of a D-enzyme: The enantiomers of HIV-1 protease show reciprocal chiral substrate specificity." Figure 3 in the same report (p. 1447) was inadvertently printed upside down. The labels "L-HIV protease" and "D-HIV protease" were therefore under the wrong illustrations. The correct figure is printed below. [See figure in the PDF file] PMID- 1631539 TI - AIDS research shifts to immunity. PMID- 1631540 TI - The perils of involving Congress in a 'catfight'. PMID- 1631542 TI - Are chemists girl crazy? PMID- 1631541 TI - Science funding. Is the wolf finally at the door? PMID- 1631543 TI - The promise and pitfalls of molecular genetics. PMID- 1631544 TI - Megascopic eukaryotic algae from the 2.1-billion-year-old negaunee iron formation, Michigan. AB - Hundreds of specimens of spirally coiled, megascopic, carbonaceous fossils resembling Grypania spiralis (Walcott), have been found in the 2.1-billion-year old Negaunee Iron-Formation at the Empire Mine, near Marquette, Michigan. This occurrence of Grypania is 700 million to 1000 million years older than fossils from previously known sites in Montana, China, and India. As Grypania appears to have been a photosynthetic alga, this discovery places the origin of organelle bearing eukaryotic cells prior to 2.1 billion years ago. PMID- 1631545 TI - Peptide binding by chaperone SecB: implications for recognition of nonnative structure. AB - The molecular basis for recognition of nonnative proteins by the molecular chaperone SecB was investigated with an in vitro assay based on the protection of SecB from proteolysis when a ligand is bound. The SecB tetramer has multiple binding sites for positively charged peptides. When the peptide binding sites are occupied, the complex undergoes a conformational change to expose hydrophobic sites that bind the fluorescent probe 1-anilinonaphthalene-8-sulfonate. A model is proposed for interaction of nonnative polypeptides with both hydrophilic and hydrophobic sites on SecB. PMID- 1631546 TI - Individual-initiated public policy. PMID- 1631547 TI - Miscarriage study. AB - In the letter of 19 June 1992 (p. 1613) by Ellen C. Weaver and Stephanie J. Bird of the Association for Women in Science (AWIS), an incorrect phone number was given for the AWIS mentoring program. The correct number is 800-886-AWIS. PMID- 1631548 TI - Is this your father's NIH? And other strategic questions. PMID- 1631549 TI - Did liability block AIDS trial? PMID- 1631550 TI - Gallo aide convicted on three counts. PMID- 1631551 TI - The evolution of sexes. PMID- 1631552 TI - Swallows and scorpionflies find symmetry is beautiful. PMID- 1631553 TI - Barbary macaques challenge theory of female choice. PMID- 1631554 TI - Speeding up a chemical game of chance. PMID- 1631555 TI - Researchers get a first look at the versatile TGF-beta family. PMID- 1631556 TI - How technique is changing science. PMID- 1631557 TI - Crystal structure of transforming growth factor-beta 2: an unusual fold for the superfamily. AB - The transforming growth factors-beta (TGF-beta 1 through -beta 5) are a family of homodimeric cytokines that regulate proliferation and function in many cell types. Family members have 66 to 80% sequence identity and nine strictly conserved cysteines. A crystal structure of a member of this family, TGF-beta 2, has been determined at 2.1 angstrom (A) resolution and refined to an R factor of 0.172. The monomer lacks a well-defined hydrophobic core and displays an unusual elongated nonglobular fold with dimensions of approximately 60 A by 20 A by 15 A. Eight cysteines form four intrachain disulfide bonds, which are clustered in a core region forming a network complementary to the network of hydrogen bonds. The dimer is stabilized by the ninth cysteine, which forms an interchain disulfide bond, and by two identical hydrophobic interfaces. Sequence profile analysis of other members of the TGF-beta superfamily, including the activins, inhibins, and several developmental factors, imply that they also adopt the TGF-beta fold. PMID- 1631558 TI - Recovery from hemophilia B Leyden: an androgen-responsive element in the factor IX promoter. AB - One form of the inherited, X-linked, bleeding disorder, hemophilia B, resolves after puberty. Mutations at -20 and -26 in the clotting factor IX promoter impair transcription by disrupting the binding site for the liver-enriched transcription factor LF-A1/HNF4. The -26 but not the -20 mutation also disrupts an androgen responsive element, which overlaps the LF-A1/HNF4 site. This explains the improvement seen in patients with the -20 mutation and the failure of the -26 patient to recover. PMID- 1631559 TI - Cloning of the gamma chain of the human IL-2 receptor. AB - A third subunit, the gamma chain, of the human interleukin-2 receptor (IL-2R) was identified, and a complementary DNA clone encoding this member of the cytokine receptor family was isolated. The gamma chain is necessary for the formation of the high- and intermediate-affinity receptors, which consists of alpha beta gamma heterotrimers and beta gamma heterodimers, respectively. The IL-2R on murine fibroblastoid cells can be internalized after binding IL-2 only if the gamma chain is present; alpha and beta are insufficient for internalization. Thus, the gamma chain is an indispensable component of the functional IL-2R. PMID- 1631560 TI - Negative inotropic effects of cytokines on the heart mediated by nitric oxide. AB - The direct effects of pro-inflammatory cytokines on the contractility of mammalian heart were studied. Tumor necrosis factor alpha, interleukin-6, and interleukin-2 inhibited contractility of isolated hamster papillary muscles in a concentration-dependent, reversible manner. The nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) blocked these negative inotropic effects. L Arginine reversed the inhibition by L-NMMA. Removal of the endocardial endothelium did not alter these responses. These findings demonstrate that the direct negative inotropic effect of cytokines is mediated through a myocardial nitric oxide synthase. The regulation of pro-inflammatory cytokines and myocardial nitric oxide synthase may provide new therapeutic strategies for the treatment of cardiac disease. PMID- 1631561 TI - On somatic recombination in the central nervous system of transgenic mice. PMID- 1631563 TI - Thrombin and hemostasis: II. PMID- 1631562 TI - Unraveling the structure of IL-2. PMID- 1631564 TI - Clinical application of the synthetic thrombin inhibitor, argatroban (MD-805). PMID- 1631565 TI - Platelet function defects: a clinical review. AB - Platelet dysfunction, especially acquired forms, are common causes of hemorrhage, especially in association with trauma and surgery. Although the hereditary platelet function defects are generally quite 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 developing 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 presence 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 appropriate clinical situations. The mainstay of therapy for essentially all these defects, if bleeding is significant, is the liberal infusion of appropriate numbers of platelet concentrates. The acquired platelet function defects, of course, should also be managed by attempts to treat or control the underlying disease, if possible, and offending drugs or potentially offending drugs should promptly be discontinued. PMID- 1631566 TI - Human platelet activating antibodies. AB - Platelet antibodies identified in the plasma of three multiply transfused patients and a woman who had delivered a baby with neonatal alloimmune thrombocytopenia were investigated for their platelet activating properties. Three patients possessed multispecific HLA antibodies reactive with 90 to 100% of the cells on a lymphocytotoxic panel. These antibodies were also detected using the MAIPA assay and MAb w6/32, which recognizes an epitope common to all HLA class I molecules. In addition to HLA antibodies, three of the patients possessed platelet-specific antibodies that were identified by the MAIPA assay as anti-HPA 1a and anti-HPA-3a (one patient) and anti-HPA-1b (two patients). Each of the HLA antibodies when reacted with platelets expressing the corresponding HLA antigens, potently induced aggregation and release of ATP from dense granules. In contrast, the HPA-1b antibodies induced platelet agglutination, but failed to trigger ATP release. However, platelets coated with these latter antibodies were now refractory to subsequent stimulation by ADP. Similarly, when HLA antibodies were reacted with platelets to produce suboptimal activation, the platelets could now be stimulated only poorly or not at all by either epinephrine or thrombin. This was also true for anti-HPA-1b, which, although not inducing aggregation or ATP release by itself, was capable of almost completely blocking thrombin-induced platelet activation. The thrombin-inhibiting activity of these antibodies could partially be reversed by pretreating antibody-coated platelets with epinephrine immediately followed by stimulation with thrombin. These findings suggest that transfused platelets may either be activated or inhibited by reaction with various platelet antibodies. Therefore it is conceivable that the presence of platelet reactive antibodies in multiply transfused recipients may contribute to the increased thrombotic and hemorrhagic symptoms often observed among these patients. PMID- 1631567 TI - Thrombin-mediated increase in vascular endothelial permeability. PMID- 1631568 TI - Pharmacologic aspects of the development of selective synthetic thrombin inhibitors as anticoagulants. PMID- 1631569 TI - Kinetic considerations on the physiologic control of thrombin and factor Xa. PMID- 1631570 TI - Thrombin derivatives obtained by autolytic or limited tryptic cleavage. PMID- 1631571 TI - The prothrombin gene and its liver-specific expression. PMID- 1631572 TI - Effects of sized heparin oligosaccharide on the interactions of Chinese hamster ovary cell with thrombospondin. AB - Binding and degradation of TSP by CHO cells and adhesion of CHO cells to substrate-adsorbed TSP are mediated by cell surface PGs and inhibitable by heparin. In order to learn how these three processes are related, we studied the effects of defined heparin oligosaccharides up to 18-mer produced by nitrous acid digestion. There was a complex correlation among oligosaccharide chain length, affinity of oligosaccharide for TSP in a solid phase binding assay, and potencies of oligosaccharide in inhibition of the three cellular processes. Inhibition of degradation was more sensitive to shorter oligosaccharides than inhibition of binding. For instance, the 10-mer inhibited binding of TSP to cells by 10% and degradation by 70%. Punctate immunofluorescence of cell surface bound TSP was replaced by a diffuse pattern after incubation in the presence of the 10-mer. These results suggest that the clustering of TSP on the cell surface may trigger endocytosis and degradation. Inhibition of binding of TSP to cells, in turn, was more sensitive to midsized oligosaccharides than inhibition of cell adhesion to adsorbed TSP. Inhibition of adhesion correlated with the ability of oligosaccharides to block binding of 125I-heparin to adsorbed TSP. PMID- 1631573 TI - Zinc binding by fibrin facilitates proteolysis by a snake (puffadder) venom protease. AB - PAV protease is able to cleave between the crosslinked sites of the gamma-chain of fibrin and fibrin-derived D-dimer. The rate of digestion can be increased fourfold to tenfold by the addition of zinc ions. Although the PAV protease is a zinc-containing metalloenzyme, the enhanced rate of cleavage can be shown to be due to histidine-specific zinc binding by D-dimer. It is proposed that zinc ions cause a distortion of the inter-crosslink peptide chain, creating a novel protease-susceptible site. The physiologic relevance is uncertain due to the relatively low measured zinc binding constant Kd = 10(-3.88) M. Zinc binding could, nevertheless, create a useful fibrin-specific neoepitope for antibody recognition in vitro. PMID- 1631574 TI - Endothelial cell-mediated thrombin formation. PMID- 1631575 TI - Thrombin binding to platelet membrane glycoprotein Ib. PMID- 1631576 TI - Deep vein thrombosis: prevalence of etiologic factors and results of management in 100 consecutive patients. PMID- 1631577 TI - Thrombin induces platelet adhesion to endothelial cells. PMID- 1631578 TI - Unusual bugs in immuno-compromised hosts. PMID- 1631580 TI - Buccal carcinoma--a case comparison of two modalities of reconstruction. AB - Buccal carcinoma, though a rare disorder in this part of the world, is often advanced at the time of diagnosis requiring full thickness resection of the cheek resulting in a through and through full thickness defect of the cheek. Such a defect confronts Head & Neck Surgeons with problem of reconstruction. The author presents, compares and contrasts two modalities of reconstruction. PMID- 1631581 TI - Sudden cardiac death in the Wolff-Parkinson-White syndrome. AB - Sudden death in the Wolff-Parkinson-White syndrome is an uncommon event but strikes in otherwise healthy children or young adults, often without much warning. They tend to occur in symptomatic but have also been reported in asymptomatic individuals. Several studies have been done profiling the sudden death survivor in the Wolff-Parkinson-White syndrome. In general, they tend to be symptomatic, have a short RR interval between preexcited beats during atrial fibrillation, have multiple pathways and may be associated with familial occurrence and Ebstein's anomaly. Several noninvasive investigations can help to assess the risk for sudden death, but the gold standard remains the use of electrophysiological testing. The management of patients with documented ventricular fibrillation or resuscitation from sudden death is unquestionably ablation of the accessory pathway but for the asymptomatic patients, it is still controversial whether they should be routinely studied by electrophysiological studies. PMID- 1631579 TI - Leuconostoc bacteraemia. AB - Leuconostoc species, a gram-positive coccal bacterium that is classically moderately susceptible to ampicillin and penicillin and resistant to vancomycin is a potential pathogen in the immunocompromised host. Twenty-eight isolates were collected from patients' blood culture specimens in the year 1989-1990. The clinical history and course of nineteen of these patients were studied. Five of them recovered without any antimicrobial therapy and in eight patients Leuconostoc species was isolated with other organisms in the blood culture specimens. The question arises as to when Leuconostoc species is of clinical significance when isolated in the blood culture specimens of patients. PMID- 1631582 TI - Operative cholangiography. AB - Retrospective analysis of 174 operative cholangiograms done over a 3-year period confirms its substantial benefit when used selectively in patients with clinical criteria for common bile duct exploration. A low incidental ductal stone rate of 1.6%, together with a 3.3% false positive cholangiogram rate and a case of bile duct injury resulting from the procedure makes its routine application appear superfluous. PMID- 1631583 TI - Giant cell tumours of the sacrum. AB - Giant Cell Tumours (GCT) of the Bone is one of the commoner primary bone tumours. Although considered a benign tumour, it does occasionally metastasize to the lungs. Treatment modalities vary according to the surgical staging and the site of the tumour. Treatment is further complicated when the tumour occurs in difficult locations like the sacrum. The paper includes a review of literature into treatment options and the presentation of 3 patients with sacral GCTs, one of which also has multiple pulmonary metastases from a "benign" giant cell tumour. PMID- 1631584 TI - ECG abnormalities in Kawasaki disease and their value in predicting coronary artery aneurysms. AB - ECG abnormalities suggestive of carditis were encountered in 20 of 25 patients (80%) with Kawasaki Disease. The commonest abnormalities were raised S-T segments (11 patients), increased Q/R ratio (11 patients) and prolonged corrected Q-T interval (7 patients). Six patients had coronary artery dilatation and all resolved on subsequent 2-D Echocardiography. These six patients all had ECG changes of carditis. Such changes were present in 74% of patients with normal coronary arteries. The differences were not significant. A similar comparison between the two groups using the modified Asai scoring system failed to show the usefulness of this scoring system in predicting the risk of coronary artery involvement in our patients. PMID- 1631585 TI - Fistulotomy and marsupialisation for simple fistula-in-ano. AB - Nineteen consecutive cases of simple fistula-in-ano treated with fistulotomy and marsupialisation were retrospectively reviewed. Fourteen cases were simple intersphincteric and the remaining 5 cases were uncomplicated transphincteric fistulae. The cases were followed up for between 3 to 10 months (mean 6.9 months). There were no reports of bowel incontinence or recurrence of fistula. The advantages of this 'tissue conserving' procedure are discussed in the paper. PMID- 1631586 TI - Medico-legal implications of electro-convulsive therapy--a Singapore viewpoint. AB - The clinical characteristics of 100 consecutive cases of ECT in a state mental hospital were surveyed. The medico-legal implications with regards to indications for and consent to ECT were looked into. The findings showed that ECT was given mostly for management reasons rather than based on diagnosis. Only 2 patients out of 100 gave their own consent. The discrepancy between teaching and practice was discussed. PMID- 1631587 TI - Inheritance of susceptibility: Lamarckism revisited. AB - The familial nature of susceptibility to rheumatic fever has been known for nearly three quarters of a century but even after massive ascertainments of affected families in 5 major cities, viz Toronto, Belfast, London, Glasgow and New York, a consensus on the exact mode of inheritance could not be reached. Reduced penetrance was suggested 40 years ago and still cited today even though the fit is poor. However with the sampling bias of the observed data resolved in the recently formulated geometric continuum v(affected-1) x P(sibship) (where O less than v----infinity) all those published ascertainments clearly show a unilocal Mendelian recessive mode of inheritance. Since rheumatic fever is clearly associated with streptococcal sore throat, I have therefore demonstrated the inheritance of an acquired trait. This Larmarckian concept is explained using simple numerical examples. PMID- 1631588 TI - Changing trends in the epidemiology and management of gonococcal ophthalmia neonatorum. AB - Between June 1985 and December 1988, 58 cases of gonococcal ophthalmia neonatorum were admitted to the neonatal unit at the University Hospital (USM). Of these, 15 (25.9%) cases were due to penicillin-resistant strains of Neisseria gonorrhoea. Of the 58 cases, 56 cases were treated effectively with a single dose of antibiotic given systemically. The mean period of recovery was shorter with spectinomycin in doses of 40 mg/kg than with cefotaxime (100 mg/kg). There was no permanent sequelae in the treated cases. An increasing incidence of infection with penicillin-resistant strains of N. gonorrhoea has been observed in the area of study. PMID- 1631589 TI - Postinfarction cardiac rupture in the nineties: do we know determinating factors? AB - Postinfarction cardiac rupture (PCR) up to the present accounts for approximately 20 percent of autopsy infarcted cases, ranking only behind arrhythmias and cardiac failure in the frequency of AMI complications. We re-examined our observations of a previous anatomo-clinical study of 96 patients who underwent autopsy after death from AMI. Sixteen patients had rupture of the free wall of the left ventricle at the site of infarction. All the patients with rupture showed the following statistically significant characteristics (p less than 0.01) if compared to those without rupture: cardiac hypertrophy (heart weight 390 to 1020 gm; mean: 627.5 +/- 201 gm; left ventricular wall thickness 18 mm to 29 mm; mean: 25.17 +/- 3.6 mm), sudden death (6 cases) without premonitory symptoms or with symptoms of less than an hour's duration or reappearance of chest pain not improved by opiates before late death, that occurred 240 to 660 minutes from chest pain, recorded electrocardiograms showing sinus rhythm with unchanged ST segment (12 cases), atrioventricular block (2 cases) and junctional rhythm (2 cases). Hypertension pre-existing to the infarction was seen in 6 cases with rupture versus 9 cases without rupture (p less than 0.01). Blood pressure, heart weight and wall thickness of the left ventricle are the most increased parameters in the patients with PCR. Preventive measures against these factors can reduce PCR. PMID- 1631590 TI - Comparison of serum fructosamine and blood glucose concentrations as indices of glycaemic control in non-insulin dependent diabetic out-patients. AB - The usefulness and validity of blood glucose measurement as an index of diabetic control were assessed with reference to serum fructosamine. Two hundred and twenty-eight non-insulin dependent diabetic out-patients were studied in the usual clinical setting. Fasting blood glucose (FBG) concentration was positively correlated with serum fructosamine (r = 0.42, t = 6.78 p less than 0.01). On the basis of their serum fructosamine concentrations, patients were divided into 3 groups. They were good control (fructosamine less than or equal to 288 umol/l), acceptable control (fructosamine less than or equal to 320 umol/l) and poor control groups (fructosamine greater than 320 umol/l). The mean fasting blood glucose concentration was significantly higher in the latter than the former 2 groups. However, at each level of control, there was a wide range of FBG concentrations. Thus, the value of FBG in predicting glycaemic control is limited. Its positive predictive value was only 32%, and its overall accuracy as an index of diabetic control was only 58% though its negative predictive value was high (93%). In 162 patients with poor diabetic control as indicated by their serum fructosamine concentrations, 81 (50%) of them had FBG less than 10 mmol/l on their clinic visit day. Fasting blood glucose is therefore not a reliable measure of good diabetic control, though it is useful in predicting poor control. FBG is simple to measure, cheap and rapidly available on clinic day, thus ensuring its continuing use. Doctors should be aware of its limitations and should not rely solely on FBG to assess diabetic control. PMID- 1631591 TI - Systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is a syndrome commonly affecting young women. The clinical manifestations are extremely varied and any major organ of the body may be involved. Misdiagnosis is not uncommon in early SLE where symptoms and signs may be few. Auto-antibodies to DNA, RNA and other cell nucleus antigens are frequently present. Circulating immune complexes may deposit in major organs, causing inflammation and tissue damage by a number of mechanisms. The lupus disease is marked by exacerbations and remissions. Management is dependent on accurate assessment of clinical activity and severity. Patient education and co operation in management affect outcome of the disease. With good management, the ten year survival may exceed 90%. PMID- 1631592 TI - The fibromyalgia syndrome. AB - Fibromyalgia is a syndrome characterized by generalized aches, pains and tender points. Fatigue and unrefreshed sleep are typical features often seen. In addition, patients complain of vasospastic extremities, irritable bowel syndrome, irritable bladder syndrome, tension headaches and sexual problems. Despite the many complaints, investigations are invariably normal. Other chronic pain and fatigue syndrome may be differentiated from Fibromyalgia. The pathophysiology is unknown but mechanical factors and a sleep disorder are implicated. Non pharmacological methods of treatment are more important than drugs. This includes explanation regarding the disease, reassurance, physiotherapy, stress elimination etc. Tricyclic anti-depressants may be useful. More research is needed to better understand this condition. PMID- 1631593 TI - Electrocardiographic case. Significance of raised ST segments? PMID- 1631594 TI - Duodenal leiomyosarcoma: a report of a rare and aggressive tumour. AB - A 45-year-old Malay lady who presented with intermittent abdominal pain and a left hypochondrial mass was found to have a 10 x 8 x 5 cm duodenal tumour without local invasion at laparotomy. En bloc resection of the tumour with adequate margin of clearance was done and histopathological diagnosis of low grade leiomyosarcoma was made. Fourteen months later, she returned with multiple metastases in the liver and needed palliative chemotherapy for pain relief. Duodenal leiomyosarcomata are very rare tumour. Their prognostic indicators include biological grading, tumour size and presence of metastases. Recognition of its high malignant potential calls for close surveillance calls even after apparent curative surgery. PMID- 1631595 TI - Retinal artery occlusion in a diver. AB - The clinical manifestation of decompression disorders is highly variable, ranging from mild rashes or joint pains to central nervous system symptoms like scotomata, paralysis and death. The diagnosis is easily overlooked, especially if an occupational history is not obtained. Recompression treatment with hyperbaric oxygen is the specific treatment for decompression sickness and air embolism. Prompt recognition and treatment are vital to recovery. However, there is a place for treatment of decompression disorders and embolism even when significant delay of up to 14 days has occurred. This case report discusses decompression disorders in relation to an unskilled fisherman diver who present with retinal artery occlusion. Decompression disorder leading to retinal artery occlusion is a very rare presentation. The difficulty of diagnosis is discussed as well as the result of delayed hyperbaric treatment. PMID- 1631596 TI - A delayed unusual presentation of a penetrating foreign body. AB - Complications resulting from the penetrating percutaneous foreign bodies almost always arise in the early post injury period. Delayed presentations of previous asymptomatic foreign bodies are rare. In this case report, symptoms of tracheal irritation arose seven years following the initial penetrating shrapnel injury to the neck. Computed tomography scans enabled localisation of the foreign body at the tracheal wall and carotid sheath interface. The usefulness of this radiologic modality in the evaluation of the penetrating soft tissue injury is highlighted. A review of the phenomenon of the migrating and asymptomatic foreign body follows. PMID- 1631597 TI - Early roentgen diagnosis of retroperitoneal duodenal rupture due to blunt abdominal trauma. AB - Retroperitoneal duodenal rupture due to blunt abdominal trauma is relatively uncommon. Diagnosis is difficult because the physical signs are subtle or they are difficult to interpret. A case of retroperitoneal duodenal rupture due to blunt abdominal trauma in whom the diagnosis was delayed is reported. Radiographic features are discussed. The role of early roentgen diagnosis is stressed in order to reduce the very high mortality which is associated with delay in diagnosis and treatment. PMID- 1631598 TI - Urinary incontinence caused by prazosin. AB - Urinary incontinence is a common problem in elderly women. However, urinary incontinence secondary to the commonly used antihypertensive, prazosin, is a rare phenomenon. The possible mechanism of this drug in causing incontinence is described in this case report. The possibility of an exaggerated response to the drug by women suffering from borderline stress incontinence is highlighted. PMID- 1631599 TI - Serodiagnosis of melioidosis in Singapore by the indirect haemagglutination test. PMID- 1631600 TI - Towards a new approach for estimating indirect costs of disease. AB - Many researchers in the field of evaluation of health care doubt the usefulness of estimates of indirect costs of disease in setting priorities in health care. This paper attempts to meet part of the criticism on the concept of indirect costs, which are defined as the value of production lost to society due to disease. Thus far in cost of illness studies and cost-effectiveness analyses the potential indirect costs of disease were calculated. In the following a first step will be taken towards a new method for estimating indirect costs which are expected to be effectuated in reality: the friction cost method. This method explicitly takes into account short and long run processes in the economy which reduce the production losses substantially as compared with the potential losses. According to this method production losses will be confined to the period needed to replace a sick worker: the so called friction period. The length of this period and the resulting indirect costs depend on the situation on the labour market. Some preliminary results are presented for the indirect costs of the incidence of cardiovascular disease in the Netherlands for 1988, both for the friction costs and the potential costs. The proposed methodology for estimating indirect costs is promising, but needs further development. The consequences of illness in people without a paid job need to be incorporated in the analysis. Also the relation between internal labour reserves and costs of disease should be further investigated. Next to this, more refined labour market assumptions, allowing for diverging situations on different segments of the labour market are necessary. PMID- 1631601 TI - Quality competition in local hospital markets: some econometric evidence from the period 1982-1988. AB - This study examines whether American hospitals continued to engage in non-price or quality competition over the recent past as health care markets underwent fundamental structural changes and the economic incentives facing hospital managers were correspondingly altered. It also investigates the degree to which such rivalrous behavior contributes to losses in economic welfare. An econometric model of quality competition is specified that tests, among other things, for the effect of spending by the hospital to enhance the quality of output on annual changes in its share of the local (inpatient) market as well as the effects of competitive conditions in the local market on the annual sum spent on quality enhancement. The model is estimated with panel data on 195 acute care hospitals in the State of Florida for the years 1982-1988. The results suggest that quality competitive behavior continued unabated over this period and that it was stimulated as much by the growth in physician supply and alternative delivery mechanisms as it was by other competing hospitals in the local market. Furthermore, the results show that quality competition yields some inefficiency or waste, but much of it also meets the test of the market. PMID- 1631602 TI - Consumer information and biased selection in the demand for coverage supplementing Medicare. AB - This study examines how the relationship between health insurance knowledge and the health status of health insurance consumers influences their decisions to purchase insurance coverage. Data from the federal Medicare health insurance program for the elderly in the United States are used. The basic Medicare program provides a limited amount of coverage for health care services obtained from any provider in the private fee-for-service (FFS) market. Beneficiaries of this program may choose to supplement the basic coverage which they receive by two mechanisms: either they may purchase private insurance designed to fill some of the gaps left by the federal program ('Medigap' policies), thereby remaining in the FFS market and preserving their choice of provider, or they may enroll in health maintenance organizations (HMOs), thereby leaving the FFS market and agreeing to use only those providers affiliated with the HMO, and in return receiving broader coverage at little additional out-of-pocket cost. The study was made possible by a unique data set which combines measures of beneficiary knowledge of Medicare coverage with measures of perceived health status, socio economic characteristics, and insurance coverage choices for a sample of Medicare beneficiaries who participated in an educational workshop about their insurance coverage options. These data were used to estimate a multinomial logistic model of the determinants of insurance choices, where the options included the two listed above and a basic Medicare option. The study explicitly recognizes the interaction between insurance information and health status in health plan choice. These results show that knowledge of coverage does have a differential impact on the decision to purchase health insurance depending on health status. With a high level of knowledge, sicker beneficiaries are less likely to have basic Medicare alone, compared with HMOs or Medigap policies, while healthier beneficiaries are less likely to be enrolled in HMOs, compared with Medigap policies. This finding has important implications for the use of health status measures to adjust capitated payment formulas when knowledgable consumers have the option to enroll in HMOs or remain in the FFS environment. In the absence of health status adjusters for the HMO capitation payments, high levels of coverage knowledge may exacerbate inherent selection bias among these coverage options by healthier and sicker consumers of health insurance. PMID- 1631604 TI - The collectivisation of health insurance. AB - The question that is dealt with in this article concerns the reasons for collectivisation of health insurance. This is not the same as collectivisation of health care. The The theoretical model of Usher, with the assumption that a commodity will be socialized if and only if a majority can be found in favour of socialization, appears relevant for the explanation of the origin and growth of social health insurance. Empirical evidence for the Netherlands, where reforms in the social health insurance are going on and common sense suggests that the taste factor is not very relevant, because preferences do not diverge very much among voters. This makes the income factor dominant. Since a majority will profit from socialization of health insurance, there is a strong tendency for collectivisation. PMID- 1631603 TI - Towards a capitation formula for competing health insurers. An empirical analysis. AB - In many countries the concept of capitating health care insurers is receiving increasing attention. The main reason is, that capitation may induce health care insurers in a competitive environment to concentrate more on cost containment. However, if the adjusters on which capitation payments are based, are too global, there may be ample room for risk selection by the insurers whilst also an unfair distribution of funds over the insurers may result, thereby undermining the objectives of capitation. The prime motivation for the present study is, that the Dutch government, as part of proposals for a new, market oriented structure of health care system, is considering to capitate insurers on the basis of global parameters like age, gender and location. Our analysis based on panel data of some 35,000 individuals, shows that the proportion of variance in annual health care expenditures that can be predicted (R2) by such a global capitation formula, is only 0.024. This is less than 1/5 of our estimate of the theoretically maximum achievable R2 which amounts to 0.138, implying the existence of abundant selection opportunities, e.g. on the basis of past expenditures or other health indicators. Alternative capitation formulae incorporating prior-year's costs and reaching about 3/5 of the maximum obtainable R2, effectively remove the profitableness of selection on the basis of past expenditures. The findings suggest, however, that selection via (chronic) health status may still be profitable to some extent. Therefore, we also analyzed data from the Dutch Health Interview Survey (N approximately 20,000) which comprised better health indicators. It appeared that a capitation formula based on the global adjusters mentioned above as well as three health status indicators and several background characteristics, yields an R2 of about 0.114, which probably accounts for 3/4 of our estimate of the maximum obtainable R2. The main conclusion is, that in the short term information on prior expenditures, which is available in the files of most insurers and thus may be used for risk selection, should be included in the capitation formula. For the more distant future, the formula should be expanded with indicators of chronic health status, possibly based on diagnostic information from previous, non-discretionary hospitalizations. PMID- 1631606 TI - Some recent developments in health economics. PMID- 1631605 TI - International health spending forecasts: concepts and evaluation. AB - Health care depends on the organizational and financial decisions which constituted each national system. Since those decisions were made at various times over the preceding years under different macroeconomic conditions, current expenditures are a distributed lag function of GDP growth and inflation rates. The accuracy of forecasts from such causal econometric models are compared to exponential smoothing, moving average, and ARIMA methods. Data fro 19 OECD countries 1965-79 are used for calibration, and then ex ante forecasts are generated for 1980-87 so that actual forecast accuracy can be tested. The greatest reduction in mean absolute error was obtained with the econometric model estimated in aggregate across all 19 countries, although single-country models, exponential smoothing and international averaging were also effective. A combination of all four forecasts was more accurate than any one alone, reducing MAE by 25% relative to a constant growth projection. PMID- 1631607 TI - Econometric critique of the economic change model of mortality. AB - The application of time-series data and analysis to study the effects of changes in unemployment rates on mortality rates has been a controversial issue in health unemployment research for many years. This article presents new criticism against previous aggregate time-series regression models and concludes that these models are misspecified in functional form, and the t-ratios used in significance tests are grossly overstated. Future empirical analysis of the Economic Change Model of Mortality, i.e. the aggregate, time-series relationship between mortality rates and economic variables must pay more attention to the salient characteristics of time-series data and implications for regression results. PMID- 1631608 TI - To prescribe or not to prescribe: on the regulation of pharmaceuticals in less developed countries. AB - An important source of failure in markets and justification for government intervention in the health sector of LDCs is imperfect information. Pharmaceutical use is one area in which widespread problems have been noted [1, 2] with substantial misuse, improper diagnosis and problems of compliance noted among both the population at large and health care providers, presumably due to a lack of information concerning appropriate use. One possible instrument vis-a-vis the regulation of pharmaceuticals in LDC's (and in developed countries as well) is the decision by public health officials to make a particular drug available over the counter (OTC) to consumers or to require a prescription from a licensed professional. The choice is one of balancing two competing risks. On the one hand, allowing self-prescription by the consumers who do not have medical training risks gross errors of diagnosis and mistaken prescriptions with possibly serious health consequences. On the other hand, requiring the intervention of a skilled professional runs the risk that the patient does not receive the appropriate, potential life saving, drug at all. With medical personnel in very short supply in many parts of the developing world, the real cost (including travel time and expense) of visiting licensed medical facilities can be prohibitively high. This paper presents a very general methodology for evaluating the tradeoff between these competing risks. The problem can be considered one of determining the value of information (in the form of a more accurate diagnosis through the intervention of a skilled professional) as a particular (and costly) mechanism for obtaining this information.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1631609 TI - The economic evaluation of malaria control technologies: the case of Nepal. AB - This paper illustrates the methodological issues arising from the use of economic evaluation in a developing country context, and how economic evaluation can be applied in developing countries to draw conclusions of relevance to policy makers. The paper reports research on the cost-effectiveness of the malaria control programme in Nepal. It outlines the heirarchy of choices presented by malaria control and concentrates on the evaluation of the mix of routine strategies employed by the programme, particularly for vector control and case detection and treatment. A social perspective is taken, and emphasis placed on identifying costs falling on households, namely private expenditure on treatment and loss of days of work. Conclusions are drawn relating to the application of economic evaluation methodology to disease control programmes in developing countries. PMID- 1631610 TI - Assessing the costs and benefits of medical research: the diabetic retinopathy study. AB - Significant amounts of scarce resources are devoted to medical research, but there have been few attempts to assess whether the benefits to society of these investments exceed the costs. A method for undertaking such an assessment has been developed and applied retrospectively to the Diabetic Retinopathy Study, a major clinical trial funded by the National Eye Institute from 1972-1981. It was estimated that the trial, which cost $10.5 million, generated a net saving of $2816 million to society ($231 million when the costs of lost production are excluded) (1982 prices) and a gain to patients of 279,000 vision years. This approach could be applied prospectively in considering priorities for medical research, in conjunction with traditional criteria such as the scientific merit of the proposal and the capabilities of the investigators. The key factors affecting the economic returns from medical research are the prevalence, incidence and economic burden of the disease in question, the costs and effectiveness of the medical intervention concerned, the likely impact of the clinical trial on clinical practice and the likely timespan of benefits from knowledge obtained during the trial. PMID- 1631611 TI - The impact of recombinant human erythropoietin on medical care costs for hemodialysis patients in Canada. AB - Recombinant human erythropoietin (r-HuEPO) is an established and effective therapy for anemia related to end stage renal disease. In addition to its clinical effects, it has been associated with significant improvements in quality of life for anemic hemodialysis patients. The therapy's impact on overall medical care expenditures for these patients remains uncertain, however. In this study, we examine the costs of r-HuEPO as well as potential offsetting reductions in other medical care costs that might result from the therapy. We used data from a randomized clinical trial, a longitudinal study of hemodialysis patients and the clinical literature to estimate the impact of r-HuEPO on transfusion requirements, transfusion-related illness, hospitalization and transplant success for these patients. We estimate that for patients that otherwise would be transfused, the therapy would reduce blood requirements by nearly 10 units per patient annually and hospital use by 8 days per year. In addition, increased transplant success due to r-HuEPO might result in 150 fewer patient months of dialysis treatments each year. Comparing the dollar value of these reductions with the cost of therapy yields a base case net increase in medical care expenditures of $3425 per patient year. Under varying assumptions, the estimates range from a net cost of $8320 to a net saving of $1775 per patient year. PMID- 1631612 TI - A cost utility analysis of mammography screening in Australia. AB - Cost utility analysis is the preferred method of analysis when quality of life instead is an important outcome of the project being appraised. However, there are several methodological issues to be resolved in implementing cost utility analysis, including whether to use generalised measures or direct disease specific outcome assessment, the choice of measurement technique, and the combination of different health states. Screening for breast cancer meets this criterion as mammographic screening has been shown to reduce mortality; and it is said that earlier treatment frequently results in less radical surgery so that women are offered the additional benefit of improved quality of life. Australia, like many other countries, has been debating whether to introduce a national mammographic screening programme. This paper presents the results of a cost utility analysis of breast cancer screening using an approach to measuring outcome, Healthy Year Equivalents, developed within this study to resolve these problems. Descriptions of breast cancer quality of life were developed from surveys of women with breast cancer, health professionals and the published literature. The time trade off technique was then used to derive values for breast cancer treatment outcomes in a survey of women in Sydney, Australia. Respondents included women with breast cancer and women who had not had breast cancer. Testing of (i) the effect of prognosis on the value attached to a health scenario; and (ii) whether the value attached to a health scenario remains constant over time has been reported. The estimate of the net costs of screening are reported. The costs of breast cancer screening include the screening programme itself, the further investigations and the subsequent treatment of breast cancer cases. Breast cancer is treated in the absence of screening, many commentators claim earlier treatment is costly but there is little evidence. Therefore we have investigated current patterns of breast cancer treatment, current use of investigations for women presenting with symptoms and current use of covert mammography screening. The results are extrapolated to obtain estimates of the costs and outcomes presented as cost per healthy year equivalent. This analysis produces important information for the Australian policy debate over mammography. It also contributes to the development of cost utility analysis and the approach developed here can be applied more generally. PMID- 1631613 TI - [Aortic valve stenosis]. PMID- 1631614 TI - [Aortic valve insufficiency]. PMID- 1631616 TI - [Extracorporeal circulation]. PMID- 1631615 TI - [Treatment of aortic valve diseases]. PMID- 1631617 TI - [Surveillance of the patient]. PMID- 1631619 TI - [Oral anticoagulants, a project for patient education]. PMID- 1631618 TI - [Education of patients taking antivitamin K]. PMID- 1631620 TI - [The society of artificial heart valve bearers]. PMID- 1631622 TI - [Care, ethics and management: antagonism or synergism?]. PMID- 1631621 TI - [Follow-up of transplant patients in the day hospital]. PMID- 1631623 TI - [A day with Veronique and Emanuel. "The profession involves you all the time"]. PMID- 1631624 TI - [Aortic valve diseases. Anatomical data]. PMID- 1631625 TI - [Is there an ideal model?]. PMID- 1631626 TI - [Hepatitis B]. PMID- 1631628 TI - [Anaphylactic shock]. PMID- 1631627 TI - [Diseases of the aortic orifice]. PMID- 1631629 TI - [Antitubercular agents]. PMID- 1631630 TI - [Protocol for taking specimens for blood culture]. PMID- 1631631 TI - [Clinical examination of patients with varicose veins]. PMID- 1631632 TI - [Venous disorders and life hygiene]. PMID- 1631633 TI - [Medical treatment of varicose veins and indications for surgery]. PMID- 1631634 TI - [Treatment of leg ulcers]. PMID- 1631635 TI - [Admission by a nurse of a patient with leg ulcer]. PMID- 1631637 TI - [Writing, the stumbling block of the profession]. PMID- 1631636 TI - [Leg ulcer. When nurses teach other nurses]. PMID- 1631638 TI - [Who are you, Michele Joly-Meng?]. PMID- 1631639 TI - [The National Hospital Center of Ophthalmology Quinze-Vingts]. PMID- 1631640 TI - [Public health, community health, primary health care]. PMID- 1631641 TI - [Advantages accorded the non-medical nursing personnel in public health]. PMID- 1631642 TI - [Antifungal agents in deep mycoses]. PMID- 1631643 TI - [Pentacarinat as an aerosol]. PMID- 1631644 TI - [Anatomy, physiology and physiopathology of the venous return of the lower extremities]. PMID- 1631645 TI - [Suicide from the aspect of legal medicine]. AB - The authors analyzed 778 cases of suicide subjected to necropsy in the Institute of Forensic Medicine in Plzen in 1979-1989. They evaluated various interrelations between 19,000 data they assembled. In the discussion they draw attention to conclusions which differ those published in the literature. PMID- 1631646 TI - [Causes of death among prisoners in Eastern Bohemia 1980-1990]. AB - The authors analyzed the death of 35 subject where autopsies were made in the Institute of Forensic Medicine in Hradec Kralove during 1980-1990 who died in prisons in the eastern Bohemian region. Attention was focused on the causes and circumstances of death. In addition to atherosclerosis and injuries attention is paid to suicide and possible murder. A special problem are deaths after long-term fasts. PMID- 1631647 TI - [Detection of drugs on thin layers using potassium permanganate]. AB - The authors discuss detection of drugs and other substances during thin layer chromatography by means of an aqueous solution of potassium permanganate. Ninety drugs and other substances were divided into three groups: a) strongly reacting, b) weakly reacting, c) not reacting. It was revealed that all compounds containing non-aromatic C = C bonds or oxidizable sulphur react very intensely. Other drugs containing readily oxidized groups react also. PMID- 1631648 TI - [Suburbs in difficulty: the relegation]. PMID- 1631650 TI - [Without your own roof: living in the city during adolescence]. PMID- 1631649 TI - [The city and mental health]. PMID- 1631651 TI - [The city at risk for drug abuse and AIDS]. PMID- 1631652 TI - [The medical-psychological center of d'Ivry: a team in the heart of life]. PMID- 1631653 TI - [Bistrot: provisional inventory of space or re-create the present]. PMID- 1631654 TI - [Dossier: disorders in the city]. PMID- 1631655 TI - [When the young steer themselves by boat]. PMID- 1631656 TI - [Family-space 92]. PMID- 1631657 TI - [Affiliation of the profession of psychiatric nursing]. PMID- 1631658 TI - [Caring for the ills of the city]. PMID- 1631659 TI - [Nursing diagnoses in mental health]. PMID- 1631660 TI - [Current issues in psychoanalysis: Reich and Ferenczi]. PMID- 1631661 TI - [A patient besieged by the absurd]. PMID- 1631662 TI - [Megalopolis, megacrisis]. PMID- 1631663 TI - [Psychopathological disorders of patients]. PMID- 1631664 TI - [To be part of the nursing staff in a residential care area]. PMID- 1631665 TI - [A new function: medical-psychiatric aide]. PMID- 1631666 TI - [The educational and caring area]. PMID- 1631667 TI - [Patient team work]. PMID- 1631668 TI - [Body moulding, words from the earth age]. PMID- 1631669 TI - [Psychomotor rehabilitation in a specialized halfway house]. PMID- 1631670 TI - [From action to interaction: communication with psychotic retarded patients]. PMID- 1631671 TI - [Determination of images. Confrontation between the body image/the lived image in the chronic psychotic patient]. PMID- 1631672 TI - [The drum child]. PMID- 1631673 TI - [Family therapy admission in mental disorders]. PMID- 1631674 TI - [Program of study leading to a state nursing diploma]. PMID- 1631675 TI - [A feverish psychotic]. PMID- 1631676 TI - The (non)-compliant patient. PMID- 1631677 TI - Writing a paper for a medical journal is like cooking potatoes. PMID- 1631678 TI - Physicians' attitudes and practices regarding treatment of HIV-infected patients. AB - We conducted a statewide survey to identify physicians' experiences, attitudes, and practices related to HIV-infected patients. A random sample, stratified by medical specialty (primary care, surgery, emergency medicine), was drawn. Physicians were concerned about contagion and inadequate knowledge to care for HIV-infected patients; 40% reported refusing or referring new HIV-infected patients. Differences across medical specialty and respondents' interest in various medical education topics to remedy knowledge deficits are discussed. PMID- 1631679 TI - Uncomplicated cystitis: diagnosis and treatment at college health centers. AB - The results of recent studies have led to valuable new recommendations regarding optimal diagnosis and treatment of acute uncomplicated cystitis in women. To investigate to what degree these recommendations have been incorporated into clinical practice, we conducted a survey of all college health centers belonging to the American College Health Association regarding their current management of suspected uncomplicated cystitis. Sixty-one percent responded. The results confirm that acute cystitis is indeed frequent among college women. Nonetheless, our data show that there is a wide variation in the approach to this common problem and that many centers have not yet adopted the new recommendations for optimal diagnosis and treatment. If we are to improve the management of uncomplicated cystitis in women, we must not only learn the best medical approaches, but we must also find reliable ways of transmitting this information to clinicians. PMID- 1631680 TI - Tubo-ovarian abscess in postmenopausal patients. AB - We retrospectively reviewed 20 surgically confirmed tubo-ovarian abscesses in postmenopausal women for the period 1973 to 1989. Pain and bleeding were the two most common presenting symptoms. Nine of the 20 patients (45%) had recently had endometrial instrumentation. Fever and the presence of a pelvic mass and elevated white blood cell count, without evidence of peritonitis, were frequent findings on admission. At surgery, seven abscesses were already ruptured or leaking, 12 of 18 patients with both ovaries had unilateral abscesses, and dense adhesions were found in 11 patients. A common intraoperative complication was inadvertent bowel injury. Postoperative complications included fascial dehiscence, enterocutaneous fistula, deep venous thrombosis, and need for prolonged ventilatory support. Eight patients had a coexisting gynecologic malignancy. A high index of suspicion is required for early recognition of postmenopausal tubo-ovarian abscess. Prompt surgical exploration should be done to avoid occult rupture or sepsis. PMID- 1631681 TI - Cavitary pulmonary cryptococcosis complicating Churg-Strauss vasculitis. AB - Churg-Strauss vasculitis (CSV) is an interesting but uncommon pulmonary vasculitis. Cavitation in CSV is distinctly unusual and should prompt a work-up for other causes. We have described a case of CSV complicated by pulmonary cryptococcosis, which was treated with a novel antifungal regimen. PMID- 1631682 TI - Infection due to Ehrlichia canis in children. AB - Human ehrlichiosis has a wide spectrum of presentation. This report presents two cases that demonstrate the diversity of the manifestation of ehrlichiosis, from life threatening to a mild viral-like illness. Diagnosis requires an understanding of the epidemiology and clinical manifestation of this infection and a high index of suspicion. PMID- 1631683 TI - New diagnoses in a specialty clinic: opportunities for consultants. AB - The role consultants play in detecting disease coincidental to the reason for consultation is unclear. We sought to elucidate this function in the setting of a specialty clinic for osteoporosis. Making no specific attempt to screen for general conditions, we evaluated 760 women; any new diagnosis was found in the course of thoroughly examining the patient for osteoporosis. A total of 274 new diagnoses were counted, encompassing 68 conditions. There were 211 women (28%) in whom a new diagnosis was detected; a higher percentage of older women than younger women had a new diagnosis. A diagnosis severity grouping scheme was devised, groups C and D being those in which further evaluation was clearly indicated. The diagnoses in groups C and D accounted for 70% of all new diagnoses made, suggesting that trivial conditions were not overrepresented. The history and physical examination alone was responsible for 50% of the various conditions diagnosed and 64% of the total number of new diagnoses. The consultant has an excellent opportunity to detect disease while performing a specialty consultation. PMID- 1631684 TI - Stiff-man syndrome. AB - Stiff-man syndrome (SMS) is a rare disorder of the central nervous system characterized by painful involuntary stiffening of axial muscles accompanied by spasms. These are often precipitated by tactile or emotional stimuli, volitional movement, and startling noises. Until recently, little has been known about the pathogenesis of SMS. There is evidence now to support the hypothesis that SMS may be an autoimmune disease. This is leading to changes in the way this disease is diagnosed and treated. We describe two patients with SMS and review the pathogenesis, diagnosis, and treatment. PMID- 1631685 TI - Antiarrhythmic response to intravenously administered magnesium after cardiac surgery. AB - We evaluated the antiarrhythmic response to magnesium given intravenously to 40 patients who had had elective cardiopulmonary bypass for the surgical treatment of acquired cardiac disease. All 40 patients were found to have hypomagnesemia postoperatively as defined by a serum magnesium level of less than 1.8 mg/dL. The ventricular arrhythmias of these patients were categorized by a modified Lown grade classification. Magnesium sulfate (16 mEq, [2000 mg]) was administered, and the patients were reclassified according to their rate of ventricular ectopia. All arrhythmias of a higher grade responded to the treatment with a marked reduction in ventricular ectopia and were reclassified to a lower grade. This study supports the routine administration of magnesium sulfate, at a dose of 16 mEq, in postoperative cardiac patients who are hypomagnesemic. PMID- 1631686 TI - Stooling problems in patients with myelomeningocele. AB - In children with myelomeningocele fecal and urinary incontinence lowers self esteem and decreases social interaction. The defects in the lumbosacral spine disturb the sensory and motor nerves supplying the skin and muscles of the perianal region, including the puborectalis muscle, and the external anal sphincter. The sensations in the region, as well as the motor functions of the striated muscles suffer, compromising the dynamics of continence and the normal process of stooling and leading to incontinence and constipation. Constipation has been treated by disimpaction of stools from the colon and rectum, administration of stool softeners, and a healthy diet containing adequate bulk forming items. Incontinence has usually been managed by behavior modification of self-initiating stooling after meals and positive reinforcement of this process. This method has helped up to 75% of patients to become socially continent. Biofeedback training has been helpful in patients who have preservation of some sensorimotor functions in the perianal region and who understand and cooperate in the process of biofeedback training. The enema continence catheter has been used to empty the rectosigmoid every 48 hours; most children treated in this manner have achieved social continence. Electric stimulation of the pudendal nerves using a neuroprosthetic device has been used in some patients. The pudendal nerve is stimulated continuously to achieve continence; stimulation is discontinued only for stooling and/or urination. PMID- 1631687 TI - Efficacy of the supraclavicular route for temporary hemodialysis access. AB - The percutaneous supraclavicular approach for temporary central venous hemodialysis access was successfully used in 27 of 34 cases (79%) without significant complications and was found to be a durable technique acceptable to every patient. The supraclavicular site was used from 3 to 156 days (mean, 40 days). The average catheter life was 25 days, and 13 guidewire catheter changes among eight patients were required for catheter limb thrombosis or suspected infection. Preventable kinks resulting from technical error occurred in two catheters (5%), necessitating guidewire replacement in one. A total of 41 catheters were used, and infection was documented in one (2%). Catheters were intentionally removed in 21 patients and were removed for proved infection (1) or suspected infection (5) in the remaining six patients. No new clinical evidence of central venous stenosis or thrombosis, such as arm swelling, prominent cutaneous collateral veins, or increased venous pressure at dialysis, was observed. We suggest the supraclavicular approach as the primary route for temporary central venous hemodialysis access. Continued follow-up is necessary to substantiate the initial favorable experience with the supraclavicular technique. PMID- 1631688 TI - Pancreatic pseudocyst: diagnosis and management. AB - Diagnosis and management of pseudocysts of the pancreas often present difficult clinical problems. We reviewed our 18 patients with pancreatic pseudocysts treated between January 1985 and October 1989 to identify criteria for operative and nonoperative management based on size of the lesion on computerized tomography. Diagnostic modalities, etiology, management, and concurrent medical problems were also evaluated. Alcohol (72%) was the most common etiologic agent. Hypertension (39%), peptic ulcer disease (28%), and chronic obstructive pulmonary disease (22%) were the most common associated medical problems. CT scan was the most frequently used (100%) and most accurate (100%) preoperative diagnostic tool. Preoperative ERCP modified the treatment plan in only one patient. All pseudocysts smaller than 3 cm on CT scan were managed nonoperatively, without recurrence (mean follow-up of 3 months). The most commonly performed surgical procedure was cystogastrostomy. External drainage procedures had a higher complication rate (100% vs 14%) and higher recurrence rate (33% vs 0%) than internal drainage procedures. Attempted percutaneous drainage in one patient resulted in recurrence. Pancreatic pseudocysts less than 3 cm in diameter can be safely managed nonoperatively. CT scan remains the diagnostic tool of choice. Preoperative ERCP evaluation is of limited utility and needs further evaluation. Internal drainage procedures provide the best surgical results. PMID- 1631689 TI - Pediatric chest disease: evaluation by computerized tomography, magnetic resonance imaging, and ultrasonography. AB - The initial method for evaluating pediatric chest disease remains the plain chest roentgenogram. When more precise definition of chest disease is required, computerized tomography (CT), magnetic resonance imaging (MRI), or ultrasonography (US) may be useful. In general, CT offers the widest spectrum of applicability. MRI is especially useful because no ionizing radiation is used and images can be acquired in multiple planes. MRI is most valuable when vascular anatomy needs to be defined or when tumor invasion of the spinal canal is suspected. US is helpful in evaluating diseases of the pleura and for characterizing and localizing pleural fluid and masses. US can differentiate normal thymus from other anterior mediastinal masses. Doppler techniques are valuable in evaluating suspected pulmonary sequestration and identifying the feeding vessel. PMID- 1631690 TI - Dizzy medical writing and editing: no relief in sight. PMID- 1631691 TI - Follow-up care for emergency patients. PMID- 1631692 TI - Jones fracture: relearning an old injury. AB - No longer should the Jones fracture be confused with more proximal injuries at the base of the fifth metatarsal. Historically, the lack of differentiation of these two injuries has led to much confusion about their natural history and consequently about the best method of treatment. It is presently well understood that the more proximal injuries typically respond satisfactorily to short-term immobilization. Current studies have been able to focus on defining the varied nature of fractures in the proximal fifth metatarsal. We have learned to differentiate between acute and chronic (subacute or stress) fractures and especially to appreciate the ramifications of the injury in an active population. Although significant contributions to understanding and managing these injuries have occurred in recent years, much of what we have described in such detail was already printed in Jones' original article, which was perhaps presented in much simpler terms, but no less accurately. PMID- 1631693 TI - Murine typhus endocarditis. AB - We have described a 28-year-old male sheepfarmer who had fever, headache, chills, malaise, and aortic insufficiency. Echocardiography revealed a tricuspid aortic valve with a large vegetation on the right cusp, an enlarged left ventricle, and diastolic flutter of the mitral valve. Repeated blood cultures were negative. Seroconversion of IgG and IgM to Rickettsia typhi was found on the 13th day of hospitalization. The patient was treated with tetracycline for 1 year and remained afebrile and free of symptoms for 9 months, when he was lost to follow up. IgM and IgG fluorescent antibodies to R typhi remained positive during 8 months of the follow-up period. We believe this to be the second reported case of endocarditis due to R typhi and the first not treated surgically. PMID- 1631694 TI - Murine typhus: forgotten but not gone. AB - An occasional patient presents the classical symptoms of a disease that has become uncommon. Typhus is an example of such a disease, since it is now well contained through control of its rodent reservoir. It is readily treated with tetracycline or one of its long-acting analogues, doxycycline or minocycline. Because typhus is infrequently encountered, the physician may not initially include it in his differential diagnosis. Our case serves as a remainder that with the increasingly frequent movement of persons from one geographic area to another, the uncommon rickettsial infection, murine typhus, should continue to be in the differential of a febrile patient. Furthermore, our case underscores the importance of including typhus in the differential of typhoid fever. PMID- 1631695 TI - Carotid body tumor: diagnostic and therapeutic approach. AB - Carotid body tumor may be clinically suspected when the only clues are physiologic manifestations of carotid body dysfunction or when a palpable cervical mass is evident upon presentation. In the latter case, the physiologic signs of carotid body dysfunction are usually recognizable. We have presented the case of a patient who was completely disabled by a slowly enlarging carotid body tumor. An attempt at surgical excision of the tumor was unsuccessful because of its proximity and adhesion to vital neck structures. An endocardial pacemaker inserted to ameliorate the episodes of bradycardia and hypotension accompanied by transient complete atrioventricular block resulted in only partial and temporary relief. Finally, irradiation of the tumor induced fast shrinkage and rapid regression of symptoms. PMID- 1631696 TI - Postpartum transient blindness probably related to undiagnosed brain tumor. AB - Nausea and vomiting are so frequent under regional anesthesia during parturition that these symptoms can be misleading and may cause the clinician to overlook a potential intracranial lesion. In the case we have reported, it was not until the onset of blindness that an intracranial lesion was suspected. Although the incidence of brain tumor during pregnancy is low, it does occur with various manifestations and has been associated with blindness. Therefore, prompt neurologic investigation may be warranted in patients complaining of visual changes, even though transient blindness can occur in the absence of a neurologic lesion. PMID- 1631697 TI - Cryptococcosis of the larynx in a patient with AIDS: an unusual cause of fungal laryngitis. AB - We have presented a case of unsuspected cryptococcal laryngitis, clinically masquerading as Kaposi's sarcoma in a patient with AIDS. The spectrum of laryngeal disease in AIDS patients includes a variety of infections and neoplasms, which can be treated satisfactorily when accurate and timely diagnosis is made. PMID- 1631698 TI - Benign schwannoma of the cecum shown radiologically. PMID- 1631699 TI - Right middle lobe syndrome caused by Mycobacterium fortuitum in a patient with human immunodeficiency virus infection. AB - We have reported a previously undescribed syndrome of Mycobacterium fortuitum infection manifested as localized pulmonary disease that required lung resection and prolonged combined chemotherapy for clinical response in a patient with HIV infection. M fortuitum infections must be considered in HIV-infected patients with possible infectious pulmonary complications. PMID- 1631700 TI - Progressive systemic sclerosis causing rapidly progressive myocardial disease and death. AB - We have presented an unusually swift progression of progressive systemic sclerosis (PSS), with death from cardiogenic shock in a 22-year-old woman who had severe hypertension and acute renal insufficiency. She arrived at our hospital with pericardial tamponade and shock. Despite initial improvement after pericardiocentesis, the patient's condition soon deteriorated and she died of cardiogenic shock. PSS was diagnosed at autopsy. Although the course of PSS is frequently indolent, it may also be fulminant, leading to death before diagnosis is determined. PMID- 1631701 TI - Candidal endophthalmitis after lithotripsy of renal calculi. AB - Candidal endophthalmitis is most commonly due to hematogenous seeding of the eye by Candida albicans. Although it is most often seen as a manifestation of disseminated candidiasis in patients who are seriously ill, other patients may have candidal endophthalmitis as the only evidence of fungal infection. We have presented a case of endophthalmitis due to C albicans in a patient who had bilateral renal calculi and who had received multiple antibiotics and extracorporeal shock wave lithotripsy. PMID- 1631702 TI - Massive splenomegaly in sarcoidosis. AB - We have presented a case of massive splenomegaly. Our patient was initially thought to have lymphoma, but at operation she was found to have sarcoidosis with splenic involvement. At 2250 g, the spleen was one of the largest recorded in the literature on sarcoidosis. Although the spleen is frequently involved in sarcoidosis, a review of 6074 cases showed that the incidence of actual splenomegaly is only 10%. In 628 of these cases the authors described various degrees of splenomegaly, but the incidence of massive splenomegaly was only 3%. We conclude that sarcoidosis must be considered in the differential diagnosis of splenomegaly. PMID- 1631703 TI - Airway obstruction in the mentally handicapped. AB - We have presented a case of laryngomalacia in an 18-year-old mentally retarded woman treated with epiglottoplasty. The preoperative and postoperative appearance of the larynx during aspiration was documented using video and still photography. Diagnosis was made by fiberoptic nasopharyngoscopy and laryngoscopy. PMID- 1631704 TI - Talking to patients with HIV disease. PMID- 1631705 TI - Inpatient CPR. PMID- 1631706 TI - Compliance with therapy for cervical dysplasia. PMID- 1631707 TI - Nuance of needle sharing among intravenous drug users in Houston. PMID- 1631708 TI - Neuropathic (Charcot) arthropathy of the spine after traumatic spinal paraplegia. AB - Neuropathic (Charcot) arthropathy of the spine is a relatively rare problem that, nonetheless, must be considered in the differential diagnosis of any patient with degeneration of one or more levels of the spine associated with diminished or absent protective sensation. This study presents 15 patients in whom Charcot arthropathy of the spine developed after traumatic paraplegia. Eight were successfully treated with surgical fusion, and the remaining seven were treated nonoperatively. By the use of combined anterior and posterior fusion with extensive debridement, autogenous grafting, and posterior instrumentation, successful fusion can be achieved in patients with Charcot arthropathy of the spine. However, the surgical technique is demanding, the rehabilitation must be carefully supervised, and the postoperative complication rate remains high. The possibility of developing secondary levels of arthropathy below a previously successful fusion must be considered. PMID- 1631709 TI - Routine use of magnetic resonance imaging in idiopathic scoliosis patients less than eleven years of age. AB - The purpose of this study was to determine the incidence of intraspinal pathology presenting as idiopathic scoliosis in children less than 11 years of age and otherwise neurologically normal. Twenty-six consecutive patients (5 boys, 21 girls) with idiopathic scoliosis measuring at least 15 degrees were studied with magnetic resonance imaging. Five children (19.2%) were diagnosed by magnetic resonance imaging to have Chiari-I malformations with hydromyelia (two patients), syringomelia (one patient), intramedullary tumor (one patient) and terminal lipoma (one patient). Only two of the five patients had left thoracic curves. Intramedullary spinal cord pathology can present as scoliosis without neurologic signs. Scoliosis can be the initial neurologic sign suggesting intraspinal pathology, and magnetic resonance imaging is indicated in routine evaluation of children less than 11 years of age. PMID- 1631710 TI - Spinal stenosis with scoliosis. AB - A retrospective review was carried out on 40 patients who met the criteria of 1) having a significant lumbar scoliosis associated with spinal stenosis, with symptoms of neurogenic claudication; and 2) having been treated with posterior decompression and pedicular screw fixation techniques. The average age of the patients was 61.5 years (range, 38-77 years), and 25 of the 40 patients were female. Eighty-eight percent of the patients had significant back pain in addition to lower extremity pain. All patients had pedicular screw fixation at all levels. Zielke instrumentation was used in 24 patients, Cotrel-Dubousset instrumentation in 8 patients, and Texas Scottish Rite Hospital instrumentation in the remaining 8 patients. After surgery, there was marked improvement in regard to pain status: 34 patients (83%) had severe pain before surgery, with 38 patients (93%) reporting mild or no pain at follow-up. Average length of follow up was 44 months (range, 24-61 months). There were no deaths and no instrument related failures or pseudarthroses noted in this series. A mean correction of the deformity of 19 degrees was obtained. Average scoliosis was 37 degrees before surgery and 18 degrees at follow-up. PMID- 1631712 TI - Human disc phospholipase A2 is inflammatory. AB - Human discs have been demonstrated to contain high levels of phospholipase A2. As the enzyme responsible for the liberation of arachidonic acid from membranes, this enzyme has a theoretical inflammatory potential. Herniated lumbar discs have a higher level of phospholipase A2 than do normal discs. The purpose of this study was to evaluate the inflammatory capability of purified human disc phospholipase A2. Phospholipase A2 extracted and purified from human disc was found to be inflammatory. Its inflammatory capability was directly related to its ability to function enzymatically. When the enzyme was treated with parabromophenacyl bromide (p-BPB) to specifically alkylate the active site histidine and block catalytic activity, the ability of the modified protein to produce edema was markedly reduced. Careful regulation of the activity of this enzyme is important in vivo because its inflammatory potential could result in disc degeneration and nerve injury. PMID- 1631711 TI - A biomechanical study of the fatigue characteristics of thoracolumbar fixation implants in a calf spine model. AB - Clinical failures of internal fixation implants for the treatment of the thoracolumbar spine are generally attributed to fatigue. Few studies, however, have characterized changes in fixation rigidity with time or subjected spine implant fixation constructs to fatigue loading until failure. Fatigue characteristics of five dorsally applied spinal fixation implants were determined using lumbosacral calf spines, with an L3 vertebrectomy, loaded cyclically in combined compression (maximum 605 N) and flexion (maximum 16 Nm) for up to 100,000 cycles. Displacement transducers monitored motion at the site of instability and at the segment above the implants. Flexibility and strain at these segments were then calculated. A one-way analysis of variance showed that there were no significant differences in flexibility of the five fixation constructs (P greater than .05). A multiple Bonferroni test revealed that the AO and Kluger fixateur interne and Steffee plates, with fixation at L2 and L4, allowed significantly more strain (P less than .01) across the site of instability than did Harrington rods and Luque plates with fixation at L1, L2, L4, and L5. There were no significant differences between fixation constructs in initial strain above the implants. After 10,000 cycles, however, there were significant increases in strain across the segment above the Luque and Harrington implants (P less than .05). Failure of the AO Schanz screw occurred in three of six constructs at a mean of 73,300 cycles. The Steffee screws failed in four of five constructs at a mean of 20,800 cycles. The rods of the Kluger fixateur interne broke in four of five constructs at a mean of 47,800 cycles, and one screw slipped at 11,000 cycles. There were no metal failures in the Harrington or Luque implants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1631713 TI - Human intradiscal levels with cefazolin. AB - The administration of prophylactic antibiotics for the prevention of discitis is common in the field of spinal surgery. The purpose of this study was to determine 1) whether cefazolin administered intravenously would result in detectable intradiscal levels; and 2) if so, what the proper timing of the antibiotic bolus should be to achieve optimal intradiscal concentrations. Forty human lumbar discs were obtained during the study period. All subjects received a preoperative bolus infusion of 2 g of cefazolin during a 3-5 minute period. Serum and intradiscal samples were obtained at intervals ranging from 6 to 220 minutes after the antibiotic infusion. The respective intradiscal concentrations of cefazolin were then determined, and the findings were as follows: 1) cefazolin does diffuse into the human disc in detectable concentrations; and 2) a critical time relationship exists (15-80 minutes after a bolus administration of cefazolin) for the optimal level of intradiscal antibiotics to be achieved. PMID- 1631714 TI - Instantaneous axis of rotation as a function of the three columns of the spine. AB - A knowledge of the rotatory motion of the vertebral bodies is needed to understand the normal biomechanical behavior of the spine. The aims of this investigation were 1) to define the instantaneous axis of rotation of the lumbar spine in rotation; and 2) to study the effect of the loss of the anulus, facet joints, and ligamentous structures on the location of the instantaneous axis of rotation. The instantaneous axis of rotation was found in 10 human cadaver thoracolumbar spines by the method of Reuleaux from superimposed serial photographs. Long-segment specimens were tested to minimize the effect of the imposed axis of the testing device. The instantaneous axis of rotation was consistently posterior to the anulus in the intact spine. With isolated destruction of the columns of the spine, the instantaneous axis of rotation migrated to the remaining intact structures. Anterior releases enhance derotation by removing the primary rotatory stabilizer. Ultimate control of a rotatory deformity or instability lies in the recognition that the anterior structures have a mechanical advantage in resisting torsion. PMID- 1631715 TI - Response to steroid and duration of radicular pain as predictors of surgical outcome. AB - Prolonged structural compromise of spinal nerve roots can lead to chronic changes that surgical decompression might not be able to reverse. In this study, it was hypothesized that if there were a reversible structural pain component, a steroid injected into the patient's symptomatic nerve root should provide temporary pain relief and that these patients should have a favorable surgical outcome. It also was hypothesized that duration of radicular symptoms would correlate inversely with surgical outcome. For postoperative relief of radicular pain, the results showed that patients with pain lasting less than 1 year had a positive surgical result (89%), regardless of response to steroid. Patients with pain lasting more than 1 year and who have had a positive response to steroid injected into the symptomatic nerve root (roots) had a positive surgical outcome of 85%. Patients who did not respond to the steroid and had pain for more than 1 year (95%) generally had a poor surgical outcome. Although the poor outcome in the last group might be explained in some cases by an inadequate structural correction, inadequate stabilization, or functional reasons, the majority of these failures represented irreversible changes in the neural structures. PMID- 1631716 TI - Complications of lumbar spinal fusion with transpedicular instrumentation. AB - Transpedicular screw fixation systems are coming into wide use as an adjunct to lumbar spinal fusion procedures. This 5-year series included 486 patients who underwent 533 variable screw placement procedures for discal, degenerative, and spondylolytic problems. The wound infection rate was 2.6%: 0.6% deep, 0.9% graft, and 1.1% superficial. The neural injury rate was 1.1% overall: 0.6% related to posterior lumbar interbody fusion and 0.6% related to instrumentation. Technical problems per procedure included 8.1% difficult screw placement, 5.6% nut loosening, and 4.3% screw breakage (1.1% per screw placed). Device modifications have reduced the incidence of screw breakage and nut loosening. No device-related neural injuries occurred in the last 333 procedures. With experience, the device can be applied safely without significantly increasing the risk of neural injury or morbidity. PMID- 1631717 TI - Technique and results of fixation to the sacrum with iliosacral screws. AB - This article describes the technique of iliosacral screw fixation, as well as a retrospective review of 28 consecutive patients who had spine fusion to the sacrum with iliosacral screws, with a minimum follow-up of 2 years. The study included 6 male and 22 female patients. Average age at the time of surgery was 43 years, and mean follow-up time was 3.5 years. There were no neurologic complications at final follow-up evaluation. Ninety-five percent of the patients had radiographic evidence of fusion. Three patients required iliosacral screw removal because of suboptimal intraoperative Kirschner-wire placement. Optimal intraoperative radiographic evaluation for accurate iliosacral screw placement is recommended. The use of iliosacral screws is also a useful addition to the armamentarium of the spine surgeon when fixation to the sacrum is required. PMID- 1631718 TI - Screw fixation in the human sacrum. An in vitro study of the biomechanics of fixation. AB - A load-to-failure test was used to study the biomechanical properties of sacral screw fixation in human cadaveric specimens. The goals of this study were 1) to determine the effects of the two commonly chosen sacral screw orientations of fixation characteristics; 2) to determine the effects of selected screw instrumentation linkages on the biomechanics of sacral screw fixation; 3) to correlate the biomechanical properties with a noninvasive assessment of sacral bone density; and 4) to correlate the torque during screw insertion with these biomechanical properties. The bone density of each specimen was measured with quantitative computed tomography. A screw was inserted from the dorsal surface either anteromedially or anterolaterally into the body of S1, and the torque needed to insert each screw was measured. The screw head was attached to a constrained or semiconstrained loading linkage. Force was applied to the screw in an inferior direction until the maximum load was achieved. The maximum load, screw translation, rotation at maximum load, and initial compliance of the bone screw interface were determined. It was found that the anteromedial screw orientation, combined with a rigidly constrained loading linkage, resulted in the greatest maximum load to failure, the least screw rotation, and the least initial compliance of the four groups studied. The maximum load and the initial stiffness of bone-screw fixation increased significantly with bone density. Torque measurements correlated significantly with maximum load to failure, initial interface stiffness, and bone density. It was therefore concluded that bone density and torque measurements can be useful in assessing sacral screw fixation. PMID- 1631720 TI - North American Spine Society. 6th annual meeting. Keystone, Colorado, July 31 August 3, 1991. PMID- 1631719 TI - The use of preoperative erythropoietin in scoliosis surgery. PMID- 1631721 TI - Spinal surgery of the future. PMID- 1631722 TI - Atlantoaxial lateral mass osteoarthritis. A frequently overlooked cause of severe occipitocervical pain. AB - Localized C1-C2 lateral mass osteoarthritis is a degenerative disorder of the upper cervical spine that has a natural history markedly different from that of degenerative afflictions of the lower cervical spine. Atlantoaxial lateral mass arthritis is a distinct cause of occasionally severe occipitocervical pain in elderly persons. In this series, the diagnosis was suggested by the medical history of nine elderly patients who presented with severe occipitocervical pain (frequently diagnosed as occipital neuralgia). Physical examination demonstrated marked restriction of rotation of the cervical spine to the affected side, and localized tenderness unilaterally at the occipitocervical junction. The diagnosis was confirmed by plain radiographs of the C1-C2 articulation (open-mouth view), demonstrating marked, usually unilateral joint-space narrowing, osteophyte formation, and subchondral sclerosis. Bone scanning demonstrated focal uptake unilaterally at the occipitocervical junction. Additional imaging studies, including computed tomography, magnetic resonance imaging, or cervical myelogram, were performed to rule out coexisting intraspinal pathology. Conservative treatment was usually successful; however, C1-C2 arthrodesis was successful for severe occipitocervical pain due to atlantoaxial lateral mass arthritis not responsive to conservative treatment. PMID- 1631723 TI - Changes in isometric strength and range of motion of the isolated cervical spine after eight weeks of clinical rehabilitation. AB - There have been no reports in the literature objectively measuring changes in strength and range of motion in patients with non-spinal-cord injuries of the cervical spine. Ninety patients participated in an 8-week training study. Diagnostic groups included patients with the following: degenerative disc (n = 6), herniated disc (n = 14), and cervical strain (n = 70). Full-range isometric strength tests were performed at eight equidistant positions in a device that constrained all motion with the exception of cervical flexion and extension. Post tests were performed following training. Significant gains were seen in strength as well as range of motion. Perceived pain was significantly reduced. This kind of testing can potentially provide the clinician with objective findings to direct patient management more adequately. PMID- 1631724 TI - Wear studies for development of an intervertebral disc prosthesis. AB - Two long-term wear behavior studies used in part of the process of selecting the best materials for a new all-metal orthopaedic spinal implant are presented. The relative and absolute wear volume rates of candidate metals were investigated through simulation of two bearing regions of an intervertebral disc prosthesis. It was determined gravimetrically that hot isostatically pressed Co-Cr-Mo alloy provided the lowest Co-Cr-Mo alloy wear debris generation. It had an average wear volume rate of 0.093 mm3/million cycles from a spring-in-pocket simulation and 0.126 mm3/million cycles from a hinge (pin-in-slot) simulation. The estimated total wear volume of a hot isostatically pressed intervertebral disc prosthesis with titanium-6%Al-4%V alloy springs was 2.9 mm3/million cycles. PMID- 1631725 TI - The natural history of thoracic disc herniation. AB - Fifty-five patients with 72 thoracic disc herniations were retrospectively reviewed in an effort to ascertain the natural history of this disease. The treatment programs given to these patients were evaluated, and 15 (27%) of the 55 patients eventually required surgery. The majority, however, did not require surgery and have continued to perform activities of daily living, some even participating in vigorous sports activities (eg, skiing) without any apparent neurologic consequences. Thoracic disc herniations, similar to cervical and lumbar disc herniations, do not always lead to major neurologic compromise. A less aggressive surgical approach therefore can be considered. PMID- 1631726 TI - [National seroepidemiologic survey, Mexico]. PMID- 1631727 TI - [Methodology of the National Seroepidemiologic Survey, Mexico]. AB - This paper briefly describes the methodology employed in the National Seroepidemiologic Survey (NSS). Among the aspects discussed are: previous studies of this kind; the master sampling frame; the sample design, the study population and sample size; the selection of diseases for study; the variables; instruments for data collection; operational design for the survey; as well as data processing and analysis. The overall response rate of the NSS was 78.4 per cent of the surveyed homes, 40 per cent of which were from rural areas (communities of less than 2,500 persons). The non-response rate was 41.3 per cent with the highest level in Baja California Sur (RNR = 26%) and the lowest in Puebla (RNR = 50.9%). The poor response in Puebla may have been due to the fact that it was the first state surveyed and served as the pilot project. The variable estimates from the NSS were similar to those found in other national surveys and the General Population Census. Therefore, these is reason to believe that the results of the NSS were representative and comparable. The final part of the paper describes the NSS projects already published, national seroprevalences, considerations concerning inference, and the laboratory procedures utilized in each project. PMID- 1631728 TI - [The National Serum Bank]. AB - A National Serum Bank was established to store sera obtained during the National Seroepidemiological Survey performed in Mexico in 1987. More than 70,000 serum samples were obtained from subjects of either sex 1-99 years of age in each of the 32 states of the country. The current collection of sera includes 28,704 male samples and 40,629 female samples. This paper describes the procedures for handling serum samples, including reception registry, storage and distribution to several laboratories for detection of measles, rubella, poliomyelitis, AIDS, diphtheria, pertussis, tetanus, brucella, salmonella, amoeba, toxoplasma, American trypanosomiasis and cysticercus. Determinations of total cholesterol were also made in order to describe its distribution and to identify the prevalence of hypercholesterolemia. PMID- 1631729 TI - [Seroepidemiology of measles in Mexico]. AB - Measles is an illness of universal distribution and great social impact. According to the WHO, the annual deaths due to this disease amount to more than a million children in the world. The objectives of this paper are to estimate the seroprevalence of titer of antibodies to measles in the population of 12 to 59 months of age in Mexico and identify the determinants of the immunity state. From the National Seroepidemiology Survey, 5,232 blood samples of children between 12 and 59 months of age, were analyzed, their blood samples were considered positive when the antibody titers were greater or equal to 1:4, tested by hemagglutination inhibition using sensitized erythrocytes. The National seroprevalence was 76.2 per cent. By age group, an increment in positive level was observed age increased. The seroprevalence was 56 per cent in children of 12 to 24 month and 82 per cent for children 48 to 59 month of age. The history of vaccination was obtained verbally; 62.5 per cent of seropositive didn't have vaccination history and 82.5 per cent were of those vaccinated were positive. By place of residence, at rural level (populations less than 2,500 inhabitants) 74 per cent positives, compared to 79 per cent in children of urban areas. All risk factor were significant, based on a univariate analysis, being the one with greatest risk those with negative vaccine history and children of one year of age. The efficiency of the vaccine estimation was of 63.6 per cent. Risk factors related to the vinculation of immunity protection to measles or seropositives were age, and verbal history of vaccination. PMID- 1631730 TI - [Values of serum cholesterol in the Mexican population]. AB - The National Seroepidemiologic survey was carried out by the General Directorate of Epidemiology of the Ministry of Health from March 1987 to May 1988. One of the objectives of this survey was to know the mean cholesterol levels in the whole country and in each of the different states of the Mexican Republic by sex and in the different age groups. Of the 68,257 individuals studied, 39,990 (58.6%) were females and 28,267 (41.1%) males. The blood samples were processed at the Lipid Laboratory in the Endocrinology Department of the National Institute of Cardiology "Ignacio Chavez". The mean serum cholesterol levels were for the entire country 184 and 185 mg/dl in adult males and females, respectively, and 145 in males and 149 mg/dl in females in the age group below 20 years old. The northern states and two states in the southeast (Yucatan and Campeche) had the highest mean values of the country, and were found to be very similar to those observed in the United States population. When the values seen during childhood were compared with those attained on adult age, an increment of around 33 percent in the mean cholesterol levels was disclosed. This finding was similar in the different regions of Mexico as well as in the USA population. Also, the states with the highest mean cholesterol values in the young population had the highest values during adulthood (R2 = 0.90 and 0.91, for males and females). This information can be of great value for developing public health strategies to diminish the incidence of coronary heart disease. PMID- 1631731 TI - [Seroepidemiology of whooping cough in Mexico]. AB - This paper presents the results from a serological survey developed in Mexico during 1987 in order to estimate the prevalence of anti Bordetella pertussis antibodies. Agglutinins were measured in 25,666 samples taken from children one to 15 years old living throughout the country. In each case survey covered some data about social and demographic variables such as socioeconomic stratum, number of DPT vaccine doses received and urban or rural settlement, among others. Titers greater than = 1.16 and 1.32 were considered positive; analysis is based on percent prevalence and geometric means of the antibody titers. We found a 65 per cent of total seropositivity, with higher prevalences in the northern and central states. Agglutinins response was higher among females subjects than in males. Children living in rural areas and those classified as belonging to lower socioeconomic level showed the lowest seropositivity prevalences. PMID- 1631732 TI - [Seroepidemiology of Chagas disease in Mexico]. AB - The lack of information about Chagas disease in Mexico, as well as the controversy concerning its importance, was the basis for the seroprevalence study of Trypanosoma cruzi in the National Seroepidemiology Survey (NSS). This information was representative of the national situation with regard to disease prevalences and other factors related to the nation's health. Unfortunately the NSS was not a very good information source for the study of trypanosomiasis americana, because its coverage in the disperse rural areas was poor. Nevertheless, the results of the NSS indicated that Chagas disease has an irregular distribution in Mexico with seroprevalences of 1.6, 0.5 and 0.2 for the different dilution levels used in the evaluation. The survey data showed Chagas disease to be less important than that mentioned by other authors. The NSS data confirmed the areas of disease transmission already reported and identified some new ones in Hidalgo, Chiapas and Veracruz. The survey also detected migratory workers with Chagas antibodies in Baja California border cities, a situation which indicates a risk for blood transfusion in areas of the country presumed to be free of the disease. Three quarters (74.5%) of the seropositive population were less than 39 years old. Moreover, the fact that children of less than four years were infected suggests that natural transmission is still very important in some areas. Although the seroprevalences were greater in the lower socio-economic groups, some persons of the higher socio-economic level were also affected. This situation may be explained by the fact that many of these persons own vacation homes in tropical areas. PMID- 1631733 TI - [Seroepidemiology of cysticercosis in Mexico]. AB - The seroprevalence of cysticercosis indicate that there is a high risk of contact with Taenia solium in Mexico, including both genders and all regions, socioeconomic group, and ages. There are some statistically significant differences in risk of contact, affecting principally the center and southeast of the country, rural areas, handicapped persons, children, old people and women. However, these differences are small. This study emphasizes the fact that the risks of infection by Taenia solium are important in all groups, and therefore, the programs for the control of this disease should be focused at the entire population and emphasize strategies for social development. PMID- 1631734 TI - [Determining factors of rubella in the 10 to 14 year-old population in Mexico]. AB - The clinical and epidemiological importance of rubella relates to its teratogenic effects. When this disease occurs in children, adolescents and adults, it is usually benign. On the other hand, these age groups are source of disease transmission to pregnant women. The serology studies on rubella carried in Mexico prior to 1974, detected seropositivity levels from 87.1 to 97.7 percent in children younger than 14 years of age. In contrast, the National Seroepidemiology Survey (NSS) (1988) reported a much lower seropositivity (69.3%) in children of the same age group, and a rate of 80 percent in women of reproductive age. This situation is a particular problem for Mexico where a high proportion of the pregnancies occur during adolescence. While previous research has commented on descriptive measures of seroprevalences in women, this study, which is based on a logistic regression model, has the purpose of identifying the factors associated with the immunological status of girls between 10 and 14 years of age. The variable which showed the most evident relation to the antibody levels for rubella was years of schooling. The odds ratios (OR) for seropositivity among those who finished secondary schooling was 2.05 times (CI 1.28-2.56) that of the illiterate group. Other statistically significant variables were related to residence, urban vs rural (OR = 1.69; CI 1.48-2.12) and age, 10 vs 14 years (OR = 1.93; CL 1.69-2.42). Based on the multivariate model, it was observed that the girls with a greater risk of seropositivity were those who live in urban areas, attend secondary school, and are 14 years of age, with an OR = 4.05 (G = 6,756.4 and 5,580 gl; p less than .001). The study concludes with the following considerations: the immunological levels of girls from 10 to 14 years of age are low, and the results of the NSS suggest that Mexican public health authorities should evaluate the policy of vaccination against rubeola in the population potentially at risk, and that the factors associated with the disease, in descending order, are: years of schooling, age, and place of residence. It is also necessary to carry out analytic studies which will identify the risks and the etiology of congenital malformations which are likely to have been associated with the occurrence of rubeola virus during pregnancy. PMID- 1631735 TI - [Seroepidemiology of toxoplasmosis in Mexico]. AB - This article presents to the results of the National Seroepidemiology Survey with regard to the prevalence of toxoplasmosis in Mexico. Some theoretical aspects of the disease are discussed, and the prevalences found in earlier reports are presented. The study measured 29,279 blood samples from persons in all 32 states of Mexico, for both sexes, all ages, and socio-economic groups. The samples were processed by indirect immunofluorescence for antibody titers of 1:16 and 1:128. Positivity levels were stratified by age, sex, socioeconomic level, place of residence, education level, number of persons in the family, state, and with or without rights to care in the social security medical institutions. The results pointed to greater prevalences in the costal areas, in lower socioeconomic levels, and a high incidence in women of reproductive age. Also included are a discussion of socio-economic aspects and the potential role of the domestic cat. PMID- 1631736 TI - [Seroepidemiology of brucellosis in Mexico]. AB - Brucellosis is an important and widely distributed zoonosis in Mexican cattle which also affects an unknown proportion of the human population. This report presents the brucellosis antibody levels registered in the National Seroepidemiology Survey (NAS) in sera obtained from 66,982 healthy persons from one to 98 years of age and determined by the test of plaque microagglutination. Seroprevalences by states ranged from 0.24 per cent in Morelos to 13.5 per cent in the state of Mexico. The national mean was estimated to be 3.42 per cent. The analysis showed no statistical differences for brucellosis antibody levels by urban and rural residence and by density of family sleeping areas (three or more persons vs. one or two persons per bedroom). Adults between 20 and 39 years of age had greater seropositivity and children from one to nine years had the least. Women were most affected and had 48 per cent more seropositivity than men. According to the information obtained in the study, brucellosis in Mexico has the following characteristics: it is related to gender but not to occupation; affects persons in all age groups, social strata and is independent of size of the community of residence. Historically, brucellosis has been an endemic disease in Mexico. Recently an increasing incidence has been reported, and this is possibly due to a better national notification system. PMID- 1631737 TI - [Antibodies against Entamoeba histolytica in the Mexican Republic. 1974]. PMID- 1631738 TI - [Endoscopic bipolar coagulation of acute gastroduodenal hemorrhage]. AB - The authors describe one possible way of endoscopic haemostasis, i.e. by bipolar coagulation. First they give an account of the principle of the method and technique of coagulation. Then they demonstrate on their own group of patients with haemorrhage into the gastroduodenum a 71% effectiveness of haemostasis by this method. In another 10% a temporary effect was achieved with the possibility of effective supplementation of the blood volume and thus an improved prognosis of surgery. In case of failure, in particular haemorrhage according to Forest Ia, they warn against any delay of surgery. PMID- 1631739 TI - [Salmonellosis and shigellosis in the differential diagnosis of acute abdomen]. AB - There are only very few reports in our literature on problems and pitfalls of the differential diagnosis and present incidence of acute abdominal salmonellosis and shigellosis. Based on evaluated results of a three-year investigation from their department the authors draw attention to the relatively frequent concurrent incidence of acute abdomen and infectious diarrhoeal disease, the difficulty of differential diagnosis and indication of surgery even when the results of cultivation examinations are known due to the common interlinked symptomatology and coincidence. The symptoms imitating acute abdomen in infectious diarrhoeal diseases predispose by concentration of infectious patients in surgical departments the development of nosocomial infections and epidemics. PMID- 1631740 TI - [Hemorrhage in severe distortion of the ankle joint]. AB - The author describes a case of severe distorsion of the talus associated with rupture of the lig. fibulotalare anterius with complicating haemorrhage from the injured art. malleolaris anterior lateralis. This injury was referred to their department only two weeks after the injury. The author describes the therapeutic procedure and resulting therapeutic effect. PMID- 1631741 TI - [Surgical treatment of anal fissures]. PMID- 1631742 TI - [Primary resection of the large intestine]. AB - The authors evaluate their own group of 49 patients subjected in 1982-1990 to primary resection of the large intestine with an immediately established anastomosis. 32 patients (65.31) recovered per primam and were discharged on average after 14.9 days. A disorder of the anastomosis was recorded in 5 patients, i.e. on 10.2%. In the conclusion the authors express conditions essential for the safety of these operations. PMID- 1631743 TI - [Classification of acute pancreatitis in correlation with serum protease levels]. AB - Based on previous work of their own and data in the literature the authors outlined diagnostic and classification criteria of acute pancreatitis. The latter were applied in a prospective study. Thus a group of 71 patients with acute pancreatitis was obtained. In 10 patients of this group at the same time intervals and while the same therapeutic procedures were used, the serum protease levels were followed up. The authors assumed that it will be possible to express thus objectively the severity of the disease and to diagnose in time necrotizing forms of acute pancreatitis. The results re demonstrated the feasibility and suitability of this procedure only for assessment of the severity of the disease. PMID- 1631744 TI - [Gallbladder carcinoma]. AB - The authors analyze a group of 34 operated patients with carcinoma of the gallbladder operated in 1984-1990. Before operation the diagnosis was established only in 6% of the patients. The authors draw attention to certain symptoms which could lead to the diagnosis of the disease on the basis of clinical and paraclinical examination. Even in recent years the incidence of this disease is not declining, difficulties with early diagnosis persist, in the majority the finding before operation cannot be resolved and only 1-5% patients survive for 5 years (due to several incidentally detected cases of carcinomas during operations performed on account of concrements). The necessity of early treatment of all biliary diseases is still urgent. PMID- 1631745 TI - [Personal experience with comprehensive treatment in diabetic gangrene]. AB - The author presents results of treatment of 262 patients with diabetic gangrene, necrosis and phlegmons; he mentions the complex of therapeutic measures incl. acral and high amputations, analyzes the causes of difficulties associated with therapy of ischaemic and infectious affections of the diabetic foot and possibilities how to improve the present unsatisfactory state of the problem. PMID- 1631746 TI - [Inflammation of the thyroid gland from the aspect of surgical treatment]. AB - The authors submit surgeons' and endocrinologists' views on treatment of thyroiditis. In the course of a 16-year period an acute spell of thyroiditis was treated by surgery only twice, once a case of subacute thyroiditis, and in all other 348 instances chronic thyroiditis was involved. In the latter group Hashimoto's thyroiditis predominated. Among various controversial reports concerning its treatment the authors maintain that surgery is suitable after failure of short-term conservative therapy. The extent of the operation usually corresponds to total thyroidectomy. PMID- 1631747 TI - [Comments on Wang's method of preparation of the recurrent laryngeal nerve in total thyroidectomy]. AB - The authors focus their attention on the problem of preparation of the recurrent laryngeal nerve in total thyroidectomy. Similarly as the majority of authors, the present authors use as the main guide during preparation of the recurrent nerve its relationship to the lower thyroid artery. As an alternative procedure they mention Wang's method which they tested in several tens of total thyroidectomies. In the submitted paper they discuss the advantages and disadvantages of this method. PMID- 1631748 TI - [Fibrin glue and wound healing]. AB - Bioadhesive systems used in medicine must meet certain prerequisites on which their application depends. A very important relationship is that of glue and tissue, irritability, the influence on regeneration of tissue cells and histotoxicity. The authors evaluated in an experimental study the necroptic appearance of the peritoneal cavity, the microscopic character of the scar and histological appearance of tissue after treatment of an induced hepatic and lienal rupture in 28 rabbits and 28 baby pigs, using fibrin tissue glue. The typical properties of the adhesive fibrin system ensue from its physiological properties. Filling the wound enhances natural biological processes of healing. The tissue reaction to the applied tissue fibrin coagulum is favourable. The treated parenchymatous organs, liver and spleen, healed by a smooth scar. The number of adhesions in the peritoneal cavity in all thus treated experimental animals after treatment of the spleen was similar. Fewer adhesions were observed when using glue for repairing liver injuries in rabbits. The macroscopic appearance of the scar was similar, the scar was less visible in the liver parenchyma. The histological appearance was similar. The glue did not damage the tissue surrounding the parenchyma and did not act as a foreign body. The assessed results confirm the harmlessness of the fibrin glue, tissue tolerance and satisfactory healing with out a reaction to alien material. After healing the fibrin glue replaced by natural fibrous tissue. PMID- 1631749 TI - [The contribution of Academician Jirasek to cardiovascular surgery]. PMID- 1631750 TI - [Extra-anatomic bypasses in reconstructive vascular surgery in the lower extremities]. AB - Extra-anatomic Bypass was used in 36 patients for limb salvage at the Department of Surgery, University Hospital in Pilsen in a period of almost eleven years (1th January 1981-1th November 1991) constituting 8.2% of all vascular reconstructions. Amputation rate was 22.2% and mortality rate 8.3% (without direct connection with reconstruction). Extra-anatomic reconstruction was used in such cases only where the anatomic bypass was excluded for general or local causes. PMID- 1631751 TI - [Reconstruction of the femoro-popliteal and peripheral portion in saphenous insufficiency]. AB - Implantation of a venous bypass is the best method of infraarticular and crural reconstructions. In 30%, however, a suitable saphenous vein is not available. If on account of severe ischemia revascularization is necessary, an alternative method must be selected. From a total number of 326 peripheral reconstructions with a distal anastomosis into the distal popliteal artery or crural artery the authors had to use instead of a long venous bypass a subsidiary reconstruction in 145 patients (44.6%). The authors implanted composite venous bypasses in 36 patients (24%), in 93 patients (64%) they combined a venous bypass with desobliteration of the superficial femoral artery and in 16 patients (11%) with an artificial prosthesis. For the end-to-end anastomosis of the prosthesis and vein the authors suggested a plastic operation by means of a venous patch which makes a short anastomosis possible with a smooth transit from a wide prosthesis into a narrow vein. The authors assume that in future ever more frequently the combination prosthesis and vein in the shape of a jump bypass will be preferred to other reconstructive methods, as it is relatively simple and rapid. Their hitherto assembled experience with this methods is favourable. PMID- 1631752 TI - [Metabolic aspects of hypothermic extracorporeal circulation]. AB - The submitted paper is devoted to some aspects of metabolic and immunity reactions of the organism to extracorporeal circulation. The authors focused attention in particular on a correlation of the whole-body oxygen consumption and the blood sugar level. Surprising findings comprise the rise of the whole-body oxygen consumption which occurs before the tissue temperature rises. As far as toxic oxygen radicals are concerned, their release is individual. It is, however, important that during the perfusion proper the activation of the immune system is suppressed. The course of the extracorporeal circulation was satisfactory from the clinical aspect; despite that it cannot be considered physiological, as also apparent from some biochemical findings. PMID- 1631753 TI - [Angiodysplasia]. AB - Angiomatous developmental changes are the therapeutic object of attention as regards elective interventions in particular in plastic surgery. Their complications in some body cavities, in particular haemorrhage or compression of organs, are usually dealt with by general surgeons and occasionally by vascular surgeons. Diseases of the central nervous system are the domain of neurosurgeons. After a general analysis of the problem of angiodysplasia, the author discusses three successfully operated patients with angiodysplasia of the stomach, spleen and small intestine which were manifested in two instances by severe haemorrhage and in one instance by compression of the surrounding tissues. PMID- 1631754 TI - [Mesenteric venous thrombosis as an unusual serious surgical complication in salmonellosis]. AB - The authors describe a case of an extensive relapsing mesenterial thrombosis associated with an intestinal infection caused by Salmonella enteritidis. The disease had a fatal course, despite treatment based on contemporary knowledge. The authors discusses the method of treatment, emphasize the necessity of full heparinization and second look operation after extensive resection of the gut. They draw attention to the fact that a relapse of an apparently trivial salmonellosis can influence in a decisive way the results of treatment. PMID- 1631755 TI - [Aorto-enteric fistula as a cause of massive gastrointestinal hemorrhage]. AB - The authors describe a rare complication following femoral reconstruction operations, i.e. an aorto-enteral fistula associated with massive gastrointestinal haemorrhage. They draw attention to limited diagnostic possibilities and sometimes the necessity to perform urgent laparotomy. The diagnosis is facilitated by endoscopy, CT, sonography and aortography. Endoscopy can determine the site of haemorrhage, not its cause. At present when there is a high number of vascular reconstruction operations, this possibility should be taken into account. The authors recommend to prevent this complication by inserting a transplant from the omentum between the intestinal wall and the prosthesis, or possibly to cover the wound by preaortal adipose and lymphatic tissue and to stitch the peritoneum to prevent direct contact. To resolve complications direct stitch may be used, a patch. More frequently it is, however, necessary to exchange the entire prosthesis and sometimes to ensure nurture by an extra-anatomical bypass. In urgent situations clamping of the aorta may be of temporary assistance. PMID- 1631756 TI - [The importance and urgency of pneumothorax]. AB - In a group of 110 subject with pneumothorax some factors are evaluated which may influence its impact and urgency. Attention is devoted to the length of the disease before surgical treatment, to the most frequent basic and accessory diseases, methods and complications of therapy, its effect and to economic aspects. Treatment on account of thoracotomy was indicated in 8.2% subjects. A total of six patients died. The authors recorded an increase of artificial pneumothorax. They draw attention to the disproportionately severe sequelae which may be due to apparently insignificant causes. Cure within one week was achieved in two-thirds of the group, the mortality increased steeply with the increasing number of relapses of the disease. PMID- 1631757 TI - [On the article by Professor Milos Hajek]. PMID- 1631758 TI - Microvascular anatomy of the hippocampal formation. AB - The hippocampal vessels were examined in 25 forebrain hemispheres injected with india ink or methylmethacrylate. There were two to seven hippocampal arteries, which measured 200-800 microns in diameter. The anterior hippocampal artery (AHA), which was present in 88.2% of the hemispheres, most often originated from the posterior cerebral and the anterior temporal arteries, that is, within the rostral hippocampo-parahippocampal arterial complex. It arose from the anterior choroidal artery in 29.4% of the hemispheres. The AHA extended between the uncus and the parahippocampal gyrus, and it supplied the head of the hippocampus. The middle hippocampal artery was constant. It most often arose from the posterior cerebral and the common temporal arteries. The middle hippocampal artery coursed just caudal to the uncus, in close relationship with the lateral posterior choroidal artery, and it usually supplied the middle part of the hippocampal formation. The posterior hippocampal artery, which existed in 94.1% of the hemispheres, most often arose from the posterior cerebral and the splenial arteries. It irrigated the caudal part of the hippocampal formation. The anastomoses connecting the posterior, middle, and the anterior hippocampal arteries were present in 29.4% of the hemispheres. The hippocampal arteries gave rise to the straight vessels, which divided into the large and the small intrahippocampal arteries. The highest density of the capillary network was noted in the pyramidal and molecular layers of the hippocampal formation. The clinical significance of the obtained microanatomical findings is discussed. PMID- 1631759 TI - Effect of graded hypoxia on cortical and spinal somatosensory evoked potentials. AB - Cortical somatosensory evoked potential (CSEP), spinal somatosensory evoked potential (SSEP), and electroencephalogram were recorded in rats under pentobarbital anesthesia. After baseline recordings in room air (21% O2), animals were subjected to a graded hypoxia at 15.75%, 10.5%, and 5.25% oxygen levels for 10 minutes. Each level of hypoxia was followed by a 15-minute reoxygenation period. With a moderate hypoxia (15.75% O2), measured latencies for the CSEP and the SSEP were not significantly different compared with baseline (p greater than 0.05). The CSEP amplitude showed a significant increase (p = 0.02) during reoxygenation after the moderate hypoxia. Change in the latency or amplitude of SSEP at 15.75% hypoxia or during the reoxygenation period was not significant compared with the room air (p greater than 0.05). No change in the electroencephalogram was noticed with the moderate hypoxia. At severe hypoxia (10.5% O2), 80% of the animals lost CSEP within 2 minutes. The loss of CSEP was concomitant with significant attenuation of the electroencephalogram waves. The SSEP was resistant to the severe hypoxia and was present in all animals. We concluded that hypoxia affects CSEP with the tendency to increase the amplitude at moderate hypoxia (15.75%) and loss of the latency and amplitude with severe (10.5%) and extreme (5.25%) hypoxia. PMID- 1631760 TI - Cranioplasty using gentamicin-loaded acrylic cement: a test of neurotoxicity. AB - Cranioplasty represents a formidable challenge for neuro-surgeons, with a significant morbidity from both early and late wound infections. Polymethylmethacrylate (PMMA) is one of the most widely used materials in this setting. Despite the advantages of this material, such as ease of handling and inert biochemical properties, it is still a foreign body that is prone to infection. We present an animal model using a gentamicin-impregnated PMMA patch to assess the neurotoxicity as well as the efficacy of using this as an alternative material to lessen the infectious morbidity in this clinical setting. In part two of our experiment, we used a PMMA patch of similar weight and surface area in a physiological saline solution to determine the rate of gentamicin elution from the patch. The results obtained appear promising with no evidence of neurotoxicity and warrant further study to assess the clinical efficacy of PMMA in this setting. PMID- 1631761 TI - Adenocarcinoma metastatic to a growth-hormone-secreting pituitary adenoma: case report. AB - Although the pituitary gland is known to harbor metastatic deposits, it is a rare occurrence for a metastatic deposit to appear in a pituitary adenoma. A case is presented of an adenocarcinoma metastatic in an acromegalic patient with a pituitary adenoma. This report adds to the literature of the unusual phenomenon of neoplasm-to-neoplasm metastasis. PMID- 1631762 TI - Enterogenous cyst at the cerebellopontine angle: case report. AB - A case of enterogenous cyst at the cerebellopontine (CP) angle is reported. A review of the literature yielded only seven cases of intracranial enterogenous cysts, and our case is the first one arising at the CP angle. The histological features, pathogenesis, and radiological and auditory brain stem response findings are discussed. PMID- 1631763 TI - Magnetic resonance imaging of a malignant transformation of an intracranial cellular blue nevus. A case report. AB - As a follow-up to a case previously reported, a rare case of malignant transformation of cellular blue nevus (CBN) in the central nervous system preoperatively diagnosed by magnetic resonance imaging (MRI) is reported. On MRI, the malignant portion of the nevus was slightly hyperintense on both T1- and T2 weighted images. In contrast, the benign portion with a great deal of melanin was hyperintense on T1-weighted image and hypointense on T2-weighted image. MRI was useful and indispensable for detecting the malignant transformation of CBN. PMID- 1631764 TI - Cerebral metastasis of malignant cardiac myxoma. AB - A rare case of bona fide cerebral metastasis of malignant cardiac myxoma is presented. The parenchymal brain tumor of a 32-year-old woman with a history of surgical operations on cardiac myxoma and jejunal leiomyosarcoma was surgically extirpated. The initial pathological diagnosis was metastatic sarcoma. Ten months later, an occlusion of bilateral carotid arteries occurred that was due to tumor emboli. The postmortem examination revealed an unusually rapid recurrence of the cardiac tumor containing sarcomatous components that were histologically identical to the tumors of the brain and the jejunum and the emboli of the cerebral vessels. Hence it was deduced that they all originated in the primary malignant cardiac myxoma. PMID- 1631765 TI - Cavernous hemangioma over the anterior fontanelle. AB - This is a report of an extremely rare case of cavernous hemangioma over the anterior fontanelle in a 5-year-old boy. Cavernous hemangioma is most common in or beneath the skin of the face, neck, and extremities and sometimes occurs in the scalp. Although cavernous hemangioma is often quoted in the literature as a differential diagnosis of a mass located at the anterior fontanelle, we could not find an illustrative case in published articles. We discuss the characteristics and differential diagnosis of cavernous hemangioma over the anterior fontanelle. PMID- 1631766 TI - Medulla oblongata germinoma in association with Klinefelter syndrome. AB - A rare case of medulla oblongata germinoma in a 19-year-old Japanese man with Klinefelter syndrome is presented. Light microscopic examination of the resected specimen showed very few lymphocytes, and an immunohistochemical study for placental alkaline phosphatase was of great diagnostic value. Up to now there have been only five cases of intracranial germ cell tumors in association with Klinefelter syndrome. These tumors were situated along in the midline structure. It is emphasized that endocrinological factors at the time of embryogenesis as well as a genetic malignant potential are important in the pathogenesis of extragonadal germ cell tumors associated with Klinefelter syndrome. PMID- 1631767 TI - Solitary plasmacytoma of the sphenoid sinus involving the pituitary fossa: a case report and review of the literature. AB - A rare case of solitary plasmacytoma of the sphenoid sinus involving the pituitary fossa is reported. A 50-year-old woman with a history of diplopia and a mass in the sphenoid sinus and the sellar region, documented by computed tomography, was referred to our department with a presumed diagnosis of nonfunctioning pituitary adenoma. The clinical and biochemical characteristics were unrevealing, but magnetic resonance imaging examination demonstrated the extrapituitary origin of the lesion. The patient was operated on by the transsphenoidal approach, and the lesion was histologically diagnosed as a plasmacytoma. Review of the literature disclosed 11 previously described cases of myelomatous disease presenting clinically as a pituitary adenoma. Our case demonstrates that magnetic resonance imaging investigation may help in distinguishing the extrapituitary origin of a mass involving the pituitary fossa. PMID- 1631768 TI - Dissecting aneurysm of the posterior cerebral artery treated with proximal ligation. AB - A rare case of a dissecting aneurysm of the P3 segment of the right posterior cerebral artery is presented that seems to have occurred in association with mild head injury. The patient was treated surgically because of repeated intramural hemorrhage and enlargement of the aneurysm. Proximal ligation produced thrombosis of the aneurysm without resulting in infarction in the region of the posterior cerebral artery. The mechanisms of the dissection, diagnosis, and treatment are briefly discussed. PMID- 1631769 TI - Solitary osteochondroma presenting as a neck mass with spinal cord compression syndrome. AB - Osteochondromas are a rare cause of spinal pathology and neurological dysfunction. A case of cervical osteochondroma with spinal cord compression is reported and the pathological, clinical, and radiological features are discussed with a brief review of the literature. PMID- 1631770 TI - Aneurysm of the fenestrated basilar artery: report of two cases. AB - This report describes two patients with fenestrated basilar artery aneurysms, and one of the patients underwent a postmortem examination. In our cases, the aneurysms arose at the proximal end of the fenestration, which involved the proximal third of the basilar artery. Subtraction angiography and oblique projections were essential in diagnosing the aneurysms. Complete neck clipping was successfully performed through a lateral suboccipital approach in the two cases. Technical aspects of neck clipping of the aneurysm of this unique location are discussed. Pathogenesis of these rare aneurysms is also discussed with clinical and histopathological data. PMID- 1631771 TI - Malignant rhabdoid tumor of the central nervous system with subarachnoid dissemination. AB - A case of primary central nervous system malignant rhabdoid tumor is presented. Clinical, radiological, and histopathological findings are described in detail. Because of a relatively long clinical course after presentation, it was possible to assess the clinical and radiological response to different treatment modalities: surgery, chemotherapy, and radiotherapy. Despite the complete clinical and radiological response that was achieved after subtotal excision, two cycles of chemotherapy, and high-dose radiotherapy, the tumor recurred within 4 months of completion of the treatment, with wide subarachnoid dissemination. Radiotherapy treatment of whole cranial axis is recommended. PMID- 1631773 TI - New drugs of 1990. PMID- 1631772 TI - Secretory meningioma with elevated serum carcinoembryonic antigen level. AB - We recently encountered a 68-year-old woman with right sphenoid wing meningioma of the secretory type accompanied by an elevated serum carcinoembryonic antigen level. This case was neuroradiologically characterized by marked brain edema. Histologically, the lesion was rated as having meningothelial components and was rich in blood vessels and pseudopsammoma bodies. Carcinoembryonic antigen, epithelial membrane antigen, keratin, and cytokeratin were immunohistochemically detected in the pseudopsammoma bodies and the cells producing these bodies. PMID- 1631774 TI - Mandibular restoration in the cancer patient: microvascular surgery and implant prostheses. AB - This article deals with state of the art reconstruction and rehabilitation of the head and neck cancer patient who requires mandibular resection. The mandible can be reconstructed by microvascular free tissue transfer of bone and soft tissue from distant body sites. The dental units and missing soft tissue contours can be supported by osseointegrated implants placed in the grafted bone. This article discusses the rationale for patient selection and sequencing of this complex and rewarding rehabilitation. PMID- 1631775 TI - Texas children biting off more than they can chew. PMID- 1631776 TI - Multidisciplinary teamwork in the treatment and rehabilitation of the head and neck cancer patient. AB - The advantages of multidisciplinary treatment planning of head and neck cancer patients is described. Planning rehabilitation concurrently with curing the malignancy results in the most effective application of treatment modalities coordinated with rehabilitative care. Concentrated multidisciplinary treatment reduces post treatment morbidity by shortening recovery and rehabilitation time. PMID- 1631777 TI - Benign cystic ovarian teratomas with prostatic tissue: a report of two cases. AB - We report two cases of the rare occurrence of prostatic epithelium in ovarian teratomas with associated transitional epithelium in one of the cases. This association of prostatic tissue with urothelium tends to reinforce the well established embryogenetic derivation of the prostate from the urogenital sinus. Local hormonal events may influence the formation of prostatic tissue from female urothelium. The histologic and immunohistological differences between adult prostate as seen in our cases and female paraurethral (Skene's) glands are discussed. PMID- 1631778 TI - Correlations of developmental end points observed after 2,4,5 trichlorophenoxyacetic acid exposure in mice. AB - A large-scale developmental toxicology study of 2,4,5-trichlorophenoxyacetic acid was conducted in four inbred strains and one outbred strain of mice. The most significant developmental effects observed were reduced fetal weight and increased incidences of cleft palate (malformation) and prenatal death (deaths/resorptions). The correlation coefficients among the proportion of deaths/resorptions, proportion of malformations, average fetal weights, and number of viable fetuses were investigated, with each variable measured on a per litter basis. Generally, the correlation coefficients between average fetal weight and number of viable fetuses were negative for the control and low-dose groups in the C57BL/6, C3H/He, and BALB/c strains. Overall, the correlation coefficients between proportion of malformations and number of viable fetuses were not significant. The correlation coefficients between proportion of malformations and average fetal weight were negative for all but one case. The correlations were weak in the control and low-dose groups, in which the malformation rates were very low, and were strong in the high-dose groups. The correlation coefficients between proportion of deaths/resorptions and proportion of malformations were generally positive at the high doses; some negative correlations were observed in control and low-dose groups. The correlation coefficients between proportion of deaths/resorptions and average fetal weight were negative for the A/JAX and CD-1 strains. In summary, the strongest relationship observed was the negative correlation between fetal weight and malformation. PMID- 1631779 TI - Identical phalangeal defects induced by phenytoin and nifedipine suggest fetal hypoxia and vascular disruption behind phenytoin teratogenicity. AB - In previous experimental studies in rabbits, we have shown that vasodilating drugs (including nifedipine) cause distal digital defects. These defects were preceded by edema, hemorrhage, and finally necrosis of the developed cartilage in the phalanges. The underlying mechanism is most likely a fetal hypoxic response, secondary to maternal hypotension and decreased uteroplacental blood flow. Since phenytoin is known to cause distal digital defects both in man and rabbits, we decided to compare the defects provoked by oral administration of phenytoin (100 mg/kg) versus nifedipine (8.3 mg/kg) to New Zealand White rabbits on days 6-18 of gestation. In order to investigate phase-specificity, phenytoin (150 mg/kg) was given on days 14-17. The result of single dose administration on day 16 of phenytoin (300 mg/kg) versus nifedipine (33.2 mg/kg) was also studied. In this latter experiment maternal heart rate was measured up to 21 hours after phenytoin administration. Phenytoin induced digital defects identical with those produced by nifedipine and caused marked maternal cardiodepression. The defects consisted of a reduction, absence, or abnormal structure of the distal phalanges. The distal phalanx of the fourth digit on the hindpaw was the first to be affected, with inclusion of other phalanges, both on the hind- and forepaws, with increasing dose. The sensitive period for induction and histological appearance of these defects was identical for phenytoin and nifedipine. These results suggest that vascular disruption due to a fetal hypoxic response lies behind phenytoin teratogenicity, as has been shown for vasodilators. A cardiodepressive action on the maternal and fetal hearts, possibly in combination with decreased uteroplacental blood flow, is discussed as a probable factor behind phenytoin teratogenicity. PMID- 1631780 TI - Microinjections of cultured rat conceptuses: studies with 4-oxo-all-trans retinoic acid, 4-oxo-13-cis-retinoic acid and all-trans-retinoyl-beta glucuronide. AB - 4-Oxo-all-trans-retinoic acid, 4-oxo-13-cis-retinoic acid and all-trans-retinoyl beta-glucuronide were intraamniotically microinjected in rat embryos on day 10 of gestation and cultured until day 11.5. A comparison of the concentration-effect relationships showed that the dysmorphogenic effects produced by these metabolites were qualitatively similar to those of parent all-trans-retinoic acid. Compared with all-trans-retinoic acid (300 ng/ml), the dysmorphogenic effects were elicited by a 2-fold higher concentration of 4-oxo-all-trans retinoic acid, an approximately 10-fold higher concentration of 4-oxo-13-cis retinoic acid and a 16-fold higher concentration of all-trans-retinoyl-beta glucuronide. A surplus of uridine 5'-diphospho-glucuronic acid, microinjected together with 300 ng/ml all-trans-retinoic acid, decreased the observed embryo toxicity of all-trans-retinoic acid, suggesting the possibility of glucuronidation in tissues of the conceptus per se. The results of the study provide further support for the hypothesis that 4-oxo-all-trans-retinoic acid and all-trans-retinoic acid are, in contrast to the corresponding cis-isomers and glucuronides, ultimate dysmorphogenic retinoids. PMID- 1631781 TI - Methotrexate-induced developmental toxicity in rabbits is ameliorated by 1-(p tosyl)-3,4,4-trimethylimidazolidine, a functional analog for tetrahydrofolate mediated one-carbon transfer. AB - Dihydrofolate reductase reduces folic acid to tetrahydrofolate as a prerequisite to one-carbon metabolism, which is required for normal embryonic de novo DNA synthesis. The developmental toxicity of methotrexate (MTX) has been attributed to MTX's ability to inhibit the activity of dihydrofolate reductase and thereby indirectly suppress one-carbon metabolism. The compound 1-(p-tosyl)-3,4,4 trimethylimidazolidine (TTI), which is structurally unrelated to folate, reestablishes one-carbon metabolism by the biomimetic transfer of single carbon units. Whether the developmental toxicity of MTX is indeed caused via suppressed one-carbon metabolism was tested in New Zealand white rabbits following concurrent maternal treatment with MTX and TTI. TTI reduced MTX developmental toxicity judged by increased mean fetal body weights, decreased percentage of malformed fetuses, and reduced incidences of major malformations. Two doses of TTI (90 mg/kg, each) at 1 hr prior to and 1 hr after MTX also reduced the developmental toxicity, but was no more effective than the single-injection regimen. Treatment with TTI alone caused no developmental toxicity. Histologically, MTX caused enlarged intercellular spaces in limb bud mesenchyme that began at 6-8 hr and increased in size until 16 hr. Mesenchymal nuclei appeared basophilic, with angular contours. Pretreatment with TTI delayed MTX induced histological changes until 20-24 hr after MTX in 36-50% of embryos and completely protected the remainder. The sequence of MTX-induced changes was not altered among affected embryos, although the severity of the lesions did not appear as great. Saline-only or TTI-only treatments caused no alterations in limb buds. These data are consistent with the concept that impaired one-carbon metabolism is indeed the fundamental process underlying MTX developmental toxicity. PMID- 1631782 TI - In vitro development of rat embryos undergoing organogenesis in heparin-plasma. AB - This study examines the use of heparin-plasma as a culture medium for mammalian postimplantation whole-embryo culture. The growth and differentiation of head fold rat embryo explants over 48 hours in a standard serum medium was compared with development of same stage explants over 48 hours in a plasma medium prepared using sodium heparin. Heparin disrupted the morphological differentiation of embryos, in a concentration-dependent manner, from 25 micrograms sodium heparin/ml media (i.e., 5 IU/ml media), with overall embryo growth being adversely affected from a concentration of 200 micrograms sodium heparin/ml media (i.e., 40 IU/ml media). Defects of cranial neural tube development were the first apparent structural anomalies resulting from culture in heparin media. Forebrain development was grossly abnormal and associated with failure of eye development. As the heparin concentration in media increased, the cephalic neural folds remained widely open and the edges became increasingly everted, although differentiation of the heart, otic primordia, and pharyngeal arch persisted. Similar concentration-dependent dysmorphogenic effects were seen when embryos were cultured in the standard serum media with added heparin. A minimum heparin concentration of 100 micrograms sodium heparin/ml media (i.e., 20 IU/ml media) was required to effectively inhibit coagulation of the plasma medium over the 48 hour culture period. Although embryonic growth was not adversely affected at this heparin concentration, morphological differentiation was severely disrupted. Therefore, heparin is not a suitable anticoagulant for the preparation of plasma for use in postimplantation whole-embryo culture. PMID- 1631783 TI - Thyroid hormone differentially regulates cellular development in neonatal rat heart and kidney. AB - The role of thyroid hormone in the control of cardiac and renal cell development was examined in neonatal rats made hyperthyroid by administration of triiodothyronine (T3, 0.1 mg/kg s.c. on postnatal days 1-5) or hypothyroid by administration of propylthiouracil (PTU, 20 mg/kg s.c. given to dams on gestational day 17 through postnatal day 5 and to pups on postnatal days 1-5). Indices of total cell number (total DNA per tissue), cell packing density (DNA per g tissue), and relative cell size (protein/DNA ratio) were evaluated from birth through young adulthood. PTU administration led to primary shortfalls in cell number that were of similar magnitude in both tissues, but persisted somewhat longer in the kidney than in the heart. Deficits in cell packing density and cell size in the hypothyroid animals were secondary to the effect on cell number, displaying smaller magnitudes of effect and a lag in appearance and disappearance of the deficits compared to that for total DNA; indeed, the phase in which tissues were restoring their cell numbers was accompanied by increased cell packing density, reflecting a more rapid restitution of cell numbers than tissue weight or cell size. In contrast to the relatively similar effects of PTU on developing cardiac and renal cells, the effects of T3 were selective for the heart. Although T3 caused general growth impairment, it evoked marked cardiac overgrowth that was accompanied by a striking increase in cell number and a small increase in cell size. The cardiac hyperplasia is unique to the developing animal, as post-replicative heart cells in adult animals show only hypertrophy in response to thyroid hormone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1631784 TI - Paternal cyclophosphamide treatment causes postimplantation loss via inner cell mass-specific cell death. AB - Treatment of the father with the anticancer alkylating agent cyclophosphamide has negative effects on embryonic development in the rat. Four-week treatment of male rats with a low dose of cyclophosphamide causes a dramatic, dose-dependent increase in postimplantation death of the progeny. Several recent studies have indicated that the paternal genome is required for the development of the extraembryonic tissues. Thus, the purpose of this study was to determine which tissues of the implanting embryo were affected by paternal exposure to cyclophosphamide. Male Sprague-Dawley rats were given cyclophosphamide (6 mg/kg/day) or saline by gavage and bred to untreated female rats after 4 weeks of treatment. Pregnant female rats were killed on day 7 of gestation, and implantation sites were dissected from the uterus, fixed, embedded in Epon for semithin serial sectioning, and stained for subsequent light microscopy. Strikingly, many of the implantation sites of affected embryos sired by treated males displayed an apparently normal trophectoderm enclosing a region of dying cells, containing dark-stained pyknotic nuclei. Very few or no inner cell mass derived embryonic cells were present in these implantation sites. Therefore, there is a selective death of inner cell mass-derived cells in day 7 implantation sites obtained from the progeny of cyclophosphamide-treated males. The results of this study suggest that treatment of the male with cyclophosphamide can affect paternal genes specifically required for development of the inner cell mass cells of the embryo, without an apparent effect on those genes required for normal trophectoderm. PMID- 1631785 TI - von Willebrand disease masquerading as haemophilia A. PMID- 1631786 TI - Hypofibrinolysis in patients with a history of idiopathic deep vein thrombosis and/or pulmonary embolism. AB - An impaired fibrinolytic activity after a venous occlusion test is the most common abnormality associated with thomboembolic disease. To better characterize the causes of abnormal responses we have measured different fibrinolytic parameters, before and after 10 and 20 min of venous occlusion, in 77 patients with a history of idiopathic deep vein thrombosis and/or pulmonary embolism and in 38 healthy volunteers. The patients had a lower mean fibrinolytic response to venous occlusion than the controls and higher antigen levels of tissue-type plasminogen activator (t-PA:Ag) and plasminogen activator inhibitor type 1 (PAI 1:Ag). Before venous occlusion, PAI-1 levels were at a molar excess over those of t-PA in all patients and controls. After 20 min of venous occlusion, the release of t-PA from the vascular endothelium resulted in a molar excess of t-PA over PAI 1 in the majority of controls (72%) but only in a minority of patients (39%). To identify patients with fibrinolytic abnormalities, reference intervals (RI) for fibrinolytic activity, t-PA:Ag and PAI-1:Ag were established in healthy controls. None of the patients had low levels of t-PA:Ag, but 17 (22%) had elevated PAI 1:Ag levels before venous occlusion and 12 (16%) exhibited low fibrinolytic activity after 20 min of venous occlusion. Ten of these were among the 17 subjects with high PAI-1:Ag levels before venous occlusion. Thus, the measurement of PAI-1:Ag levels before venous occlusion (i.e. in samples taken without any stimulation) is a sensitive (83%) and specific (89%) assay for the detection of patients with an impaired fibrinolytic response to venous occlusion. PMID- 1631787 TI - D-dimer and thrombin-antithrombin III complexes in patients with clinically suspected pulmonary embolism. AB - One hundred and fifty-six consecutive patients with clinically suspected pulmonary embolism (PE) had blood drawn to measure levels of D-dimer and thrombin antithrombin (TAT) complexes and underwent ventilation/perfusion (V/Q) lung scanning and bilateral impedance plethysmography (IPG); pulmonary angiography was performed in 10 patients. Patients were classified as: PE-positive (positive pulmonary angiography or high probability lung scan or non-high probability lung scan and abnormal IPG) or, PE-negative (normal lung scan or normal pulmonary angiography) or PE-unlikely (non-high probability lung scan and normal serial IPG and absence of venous thromboembolism in follow-up). Thirty patients were classified as PE-positive, 64 as PE-negative and 62 patients as PE-unlikely. PE positive patients were treated with anticoagulants, whereas PE-negative and PE unlikely patients were not. PE-unlikely patients were followed for 3 months with repeat IPG and clinical evaluation for the occurrence of venous thromboembolism. The sensitivities, specificities, positive predictive values and negative predictive values of the D-dimer and TAT complex assays were calculated for patients classified as PE-positive and PE-negative. In addition, the prevalences of normal D-dimer and TAT complex assays were calculated for PE-unlikely patients. Cutoffs of 300 ng/ml for D-dimer and 3.5 micrograms/ml for TAT complexes provided sensitivities of 96% for both assays, negative predictive values of 97% for D-dimer and 96% for TAT complexes and specificities of 52% for D-dimer and 51% for TAT complexes. The specificities of the assays were higher in patients without comorbid conditions and in outpatients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1631789 TI - A collaborative study to establish an international standard for alpha-thrombin. AB - Since 1975 an International Standard for Thrombin of low purity has been used. While this standard was stable and of value for calibrating thrombins of unknown potency the need for a pure alpha-thrombin standard arose both for accurate calibration and for precise measurement of thrombin inhibitors, notably hirudin. An international collaborative study was undertaken to establish the potency and stability of an ampouled pure alpha-thrombin preparation. A potency of 97.5 international units (95% confidence limits 86.5-98.5) was established for the new alpha-thrombin standard (89/588) using a clotting-assay procedure. Stability data at various elevated temperatures indicated that the standard could be transported and stored with no significant loss of potency. Ampoules of lyophilised alpha thrombin (coded 89/588) have been recommended as an International Standard for alpha-thrombin with an assigned potency of 100 international units per ampoule by the International Society for Thrombosis and Haemostasis (Thrombin and its Inhibitors Sub-Committee) in Barcelona, Spain in July 1990 while the Expert Committee on Biological Standardisation and Control of the World Health Organisation will consider its status at its next meeting in Geneva in 1991. PMID- 1631788 TI - Platelet and fibrinogen survival in calves implanted with artificial heart and ventricular assist device--correlation with autopsy findings. AB - The two main ingredients of blood clots formed on artificial surface are platelets and fibrinogen. In this study, we measured platelet and fibrinogen survival in calves implanted with total artificial heart (TAH) and left ventricular assist device (LVAD), and correlate these data with autopsy findings. Platelet survival with autologous 111In-labeled platelets was performed on nine calves implanted with TAH and five with LVAD. Fibrinogen survival with 131I labeled homologous fibrinogen was performed on six calves with TAH and three with LVAD. Platelet survival was significantly shortened in both groups of animals: 5.89 +/- 0.52 days, control 6.46 +/- 0.31 days, p = 0.0013; fibrinogen survival was normal: 8.79 +/- 1.20 days, control 8.64 +/- 1.16 days. At autopsy two calves with TAH had multiorgan thromboembolism. Two other animals with TAH and four with LVAD had focal renal infarcts. Most animals had minor clot formation within the prosthetic device. Major septic complications occurred in four calves with TAH and one with LVAD. Continuous platelet activation by artificial surface probably explains the shortened platelet survival and thromboembolic complications. PMID- 1631790 TI - Bacterial expression of biologically active high molecular weight kininogen light chain. AB - Human high molecular weight kininogen (HK), a single chain plasma glycoprotein, serves as a cofactor in the contact system of blood coagulation. After cleavage by human plasma kallikrein, the nonapeptide bradykinin is released. The HK light chain (LC) contains coagulant activity, which requires both the ability to bind the contact system zymogens, prekallikrein and factor XI, and the ability to interact with negatively charged surfaces. Since bacterial expression might not be successful if carbohydrate was required for activity, we evaluated that possibility by incubating plasma HK with endoglycosydase F. Although the procedure removed detectable N-linked carbohydrate, no change in specific activity occurred. We then developed a bacterial expression system to produce recombinant HK LC. The cDNA coding for the HK LC was prepared by polymerase chain reaction (PCR), digested with restriction enzymes EcoRI and PstI, and introduced into the bacterial expression vector pKK223-3. E. coli harboring this recombinant plasmid (pSK1) expressed HK LC upon induction with isopropylthio-galactoside (IPTG). The recombinant protein (27 kDa), when transferred onto a PVDF membrane, was recognized by monospecific polyclonal anti-HK LC-antibodies. The recombinant HK LC was purified by heparin agarose affinity chromatography to homogeneity and found to have a specific activity of 28 coagulant units per mg protein, similar to the specific activity of the LC derived by proteolytic digestion of human plasma HK. We conclude: 1) The HK LC synthesized in bacteria is biologically active, and 2) the 40% carbohydrate content of the HK LC is not required for its cofactor activity. PMID- 1631791 TI - The effect of suramin on laboratory tests of coagulation. AB - The antitrypanosomal drug suramin, which has recently been under investigation as a cancer chemotherapeutic agent, has previously been found to induce heparin-like anticoagulants in treated patients. In the currently reported work suramin is shown to have an additional anticoagulant activity that is due to direct effects of the drug on procoagulant proteins. The studies were conducted with pooled normal plasma treated in vitro with suramin and with plasma samples obtained from patients who had received the drug intravenously for 2 weeks. It is demonstrated that in plasma suramin inhibits factors V, VIII, IX, X, XI, and XII, while thrombin, prothrombin, and factor VII are unaffected. The inhibition of factor V is virtually irreversible, although the effect of suramin on the other factors is readily reversed by dilution. PMID- 1631792 TI - Analysis of intrinsic fibrinolysis in human plasma induced by dextran sulfate. AB - The analysis of normal human plasma by fibrin autography revealed four species of plasminogen activator (PA) activity related to tissue-type PA, factor XII, prekallikrein and urokinase-type PA (u-PA). The u-PA activity increased significantly by incubating plasma with dextran sulfate. This increase was coincident with both the cleavage of factor XII and the complex formation of activated factor XII with its plasma inhibitors, which were determined by immunoblotting procedure. The dextran sulfate-dependent activation of u-PA required both factor XII and prekallikrein, but did not require either plasminogen or factor XI. High molecular weight kininogen was required only at a low concentration of dextran sulfate. Thus the results indicate that the factor XII and prekallikrein-mediated activation of single chain u-PA (scu-PA) operates as a major pathway of scu-PA activation in whole plasma in contact with dextran sulfate. PMID- 1631794 TI - Lack of stability of aggregates after thrombin-induced reaggregation of thrombin degranulated platelets. AB - The stability of platelet aggregates is influenced by the extent of the release of granule contents; if release is extensive and aggregation is prolonged, deaggregation is difficult to achieve. The relative importance of the contributions of released substances to aggregate stability are not known, although stable thrombin-induced aggregates form in platelet-rich plasma from patients with barely detectable plasma or platelet fibrinogen, and ADP stabilizes thrombin-induced aggregates of platelets from patients with delta storage pool deficiency which otherwise deaggregate more readily than normal platelets. We degranulated platelets with thrombin (0.9 U/ml caused greater than 90% loss of delta and alpha granule contents) and recovered them as individual platelets in fresh medium. The degranulated platelets were reaggregated by thrombin (2 U/ml). To prevent continuing effects of thrombin, FPRCH2Cl was added when thrombin induced aggregation of thrombin-degranulated platelets reached its maximum. EDTA (5 mM) or EGTA (5 mM) added at maximum aggregation did not deaggregate these platelets, indicating that the stability of these aggregates does not depend on Ca2+ in the medium. Whereas with control platelets a combination of PGE1 (10 microM) and chymotrypsin (10 U/ml) was required for deaggregation, with thrombin degranulated platelets either PGE1 or chymotrypsin alone caused extensive deaggregation. The rate and extent of deaggregation of thrombin-degranulated platelets by a combination of PGE1 and chymotrypsin was greater than with control platelets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1631793 TI - Biochemical, thrombolytic and pharmacokinetic properties of rt-PA P47G, K49N, a substitution variant of human tissue-type plasminogen activator. AB - rt-PA P47G, K49N, a substitution variant of recombinant human tissue-type plasminogen activator (rt-PA), in which proline at position 47 and lysine at position 49 were replaced by glycine and asparagine respectively, was previously described by Ahern et al. (J Biol Chem 1990; 265:5540-5) to have an extended in vivo half-life with unaltered in vitro fibrinolytic properties. Because this variant might possess an increased in vivo thrombolytic potency, we have constructed its cDNA, expressed it in Chinese hamster ovary cells and determined its biochemical, thrombolytic and pharmacokinetic properties relative to those of home-made rt-PA and of alteplase (Actilyse). The specific fibrinolytic activities on fibrin plates were 160,000 +/- 17,000, 210,000 +/- 88,000 and 460,000 +/- 72,000 IU/mg (mean +/- SEM) for rt-PA P47G, K49N, rt-PA and alteplase, respectively, while the catalytic efficiencies for plasminogen activation (k2/Km) in the absence of fibrin were comparable (1.1 to 1.7 x 10(-3) microM-1s-1). Fibrin enhanced the rate of plasminogen activation by rt-PA P47G, K49N 100-fold and by both wild-type molecules 390-fold. Binding of the variant rt-PA to fibrin was significantly reduced, but its affinity for lysine-Sepharose was unaltered. In an in vitro clot lysis system, consisting of a radiolabeled human plasma clot submersed in plasma, 50% clot lysis in 2 h required 0.67 +/- 0.14 micrograms/ml rt-PA P47G, K49N, 0.36 +/- 0.01 micrograms/ml rt-PA and 0.17 +/- 0.01 micrograms/ml alteplase, respectively (mean +/- SEM; n = 3 or 4). At these doses residual fibrinogen levels at 2 h were in excess of 80%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1631795 TI - Inhibition by glaucocalyxin A of aggregation of rabbit platelets induced by ADP, arachidonic acid and platelet-activating factor, and inhibition of [3H]-PAF binding. AB - Glaucocalyxin A is a new diterpenoid isolated from the ethereal extract of the leaves of Rabdosia japonica (Burm f) Hara var glaucocalyx (Maxim) Hara (Labiatae) collected in the northeastern China. When it was incubated with washed rabbit platelets, glaucocalyxin A inhibited ADP- or arachidonic acid-induced platelet aggregation with IC50 values of 4.4 mumol/l, 14.1 mumol/l respectively. Glaucocalyxin A also inhibited PAF-induced aggregation of rabbit platelets which were refractory to ADP and arachidonic acid with an IC50 value of 13.7 mumol/l. Analysis of [3H]-PAF binding showed that glaucocalyxin A prevented [3H]-PAF binding to intact washed rabbit platelets with an IC50 value of 8.16 mumol/l, which was consistent with its inhibition of PAF-induced platelet aggregation. PMID- 1631796 TI - Induction of tissue factor synthesis in human umbilical vein endothelial cells involves protein kinase C. AB - Incubation of human umbilical vein endothelial cells with one of the following compounds: endotoxin, recombinant interleukin-1 beta, recombinant tumor necrosis factor alpha, allogenic lymphocyte subpopulations or phorbol ester resulted in significant induction of tissue factor synthesis. Diacylglycerol had the same effect and also enhanced synergistically the induction caused by endotoxin and interleukin-1 beta. Two different inhibitors of protein kinase C, H7 and sphingosine, inhibited tissue factor synthesis at concentrations which did not depress protein synthesis in general, suggesting that protein kinase C is involved in the processes leading to tissue factor synthesis. Cells down regulated for the tissue factor response to TPA responded essentially normally to endotoxin and interleukin-1 with regard to tissue factor synthesis. PMID- 1631797 TI - The role of venom haemorrhagin in spontaneous bleeding in Bothrops jararaca envenoming. Butantan Institute Antivenom Study Group. AB - Thirty-eight patients bitten by Bothrops jararaca were investigated. Twenty-six had signs of local or systemic haemorrhage. Twenty-two of these had incoagulable blood, and these patients were found to have low fibrinogen levels (mean 0.17 +/- 0.03 g/l), thrombocytopenia, very high thrombin-antithrombin III complex (850 +/- 184 micrograms/l) and D-dimer (170 +/- 44 micrograms/ml) antigen levels. Serum venom haemorrhagin levels were significantly higher in patients with clinical signs of haemorrhage (36.4 +/- 6.4 ng/ml) than those without (11.7 +/- 3.7 ng/ml; p less than 0.002). Twelve out of 13 patients with thrombocytopenia were bleeding. High levels of thrombomodulin (22.3 +/- 1.5 ng/ml) and haemorrhagin (35.7 +/- 7.7 ng/ml) were detected in these 12 patients, suggesting vascular endothelial damage. Haemorrhagin levels also correlated inversely with platelet count in these patients. It was concluded that thrombocytopenia is one of the main causes of bleeding in B. jararaca victims, possibly as a result of venom haemorrhagin activity. PMID- 1631798 TI - Down-regulation of urokinase secretion from a human lymphoma cell line RC-K8 by dexamethasone without inducing plasminogen activator inhibitors. AB - The plasminogen activator (PA) activity in various cell lines is suppressed by glucocorticoids. These phenomena are attributed to either a suppression of PA biosynthesis, to an increase of PA inhibitor or to a combination of both. The regulation of urokinase (UK) production in a human pre-B cell lymphoma line, RC K8, by dexamethasone (Dex) and phorbol myristate acetate (PMA) was investigated. RC-K8 is a cell line which is consistently producing a high molecular weight UK in the conditioned medium (Kubonishi, I., et al: Jpn. J. Cancer Res. 76, 12-15, 1985). The cells were cultured in RPMI-1640 with Dex or PMA for 1-4 days. UK activity was measured using a chromogenic substrate S-2444 and the antigen by an ELISA kit. PAI-1 and PAI-2 antigens were also measured by ELISA kits and the complex between PA and PAI was examined by SDS-PAGE fibrin-zymography. The UK secretion in RC-K8 cells was inhibited by cycloheximide and actinomycin D. PMA at 0.16-1.6 uM up-regulated the UK activity approximately two-fold, parallel with the antigen, whereas Dex at 1-10 uM decreased the UK expression approximately half. These were verified by SDS-PAGE fibrin-zymography. Neither PAI-1, PAI-2 nor PA/PAI complex was detected in the conditioned medium and in the cell lysate. These data suggest that PMA up-regulates the UK secretion without inducing PAIs and the down-regulation of the UK secretion by Dex results from the inhibition of the expression of UK itself but not from the induction of PAIs. PMID- 1631799 TI - Functional behaviour of mononuclear blood cells from patients with hypercholesterolemia. AB - Mononuclear cells were prepared from venous blood obtained from 20 patients with a newly diagnosed hypercholesterolemia and without clinical signs of vascular disease, and from 19 age and sex matched controls. Adhesiveness to plastic surface, phagocytic activity measured as ingestion of zymosan particles, and spontaneous motility of mononuclear cells from patients were significantly higher by 57%, 19% and 50%, respectively, when compared to controls. In controls chemotaxis induced by the chemotactic peptide FMLP was slightly higher than spontaneous motility measured in absence of FMLP, whereas in patients FMLP significantly inhibited cell motility by about 47%. With the exception of FMLP induced chemotaxis the results indicate that mononuclear cells are hyperreactive in hypercholesterolemia. PMID- 1631800 TI - A new variant of von Willebrand disease (type II I) with a normal degree of proteolytic cleavage of von Willebrand factor. AB - A variant of type II von Willebrand disease (vWd) is described in a young woman and her mother with severe lifelong bleeding histories. On electrophoresis with low-resolution agarose gels the plasma of the proband lacked large and intermediate-size multimers of von Willebrand factor (vWF) but the platelet multimeric structure was normal. On high-resolution gels, smaller multimers could be resolved into a broader central band and four satellite bands, which were much fainter than in normal plasma. In the proband plasma, the relative concentrations of proteolytic fragments of the vWF subunit were within the normal laboratory range. Since this variant of vWd appears to differ from those reported hitherto, the designation of type II I is proposed. PMID- 1631801 TI - Reduction in the ADP release from shear-stressed red blood cells by fish oil administration. AB - Fish oil concentrate (5.4 g/day) was administered to 8 young male volunteers and to 7 middle-aged male volunteers for 1 week. ADP released into the supernatant of red blood cell (RBC) suspension by a shear stress of 375/sec for 3 min was measured before and after fish oil administration. Before the administration the ADP release from shear-stressed RBCs in the middle-aged group was significantly higher than in the young group. After the administration the ADP release was reduced significantly in the young group (by 46%, p less than 0.001) and nonsignificantly in the middle-aged group (by 54%, p = 0.09). If the two groups were combined, the reduction was also significant (by 50%, p less than 0.005). This reduction was significantly correlated with the improvement of RBC filterability after fish oil administration (n = 13, r = 0.62, p less than 0.05). We suggest that the reduction of the ADP release from shear-stressed RBCs is one of the mechanisms of action of eicosapentaenoic acid against thrombotic disease. PMID- 1631802 TI - Thrombin inactivation and the effects of antithrombin and heparin in a recirculating Langendorff preparation. AB - A recirculating Langendorff preparation was developed in order to study the effects of antithrombin III (AT) and heparin on thrombin inactivation in the capillary bed. Using this technique, rat hearts were shown to inhibit approximately 50% of the recirculated thrombin, while surface-bound thrombin displayed no enzymatic activity towards recirculated fibrinogen. By displacing thrombin bound to the endothelial surface with Polybrene, thrombin enzymatic activity was found to be equally active against a synthetic chromogenic substrate (S-2238) and fibrinogen. This indicates that thrombin bound to the capillary endothelial surface is not coagulantly active, but, when displaced from the endothelium, its coagulant activity is retained. Hearts pretreated with AT or heparin had no effect on thrombin inhibition or surface-bound thrombin, although there was an uptake of both substances to the heart. These findings are in contrast with the results obtained from large vessel preparations, where pretreatment with AT increased thrombin inhibition and also demonstrated lower levels of surface-bound thrombin, and where heparin eluted endogenous AT from the endothelium. It is concluded that AT plays a more important role in the inhibition of thrombin on large vessels than in the microcapillary system where thrombomodulin is the major inactivator of thrombin. PMID- 1631803 TI - von Willebrand factor characterization of a severe dry-heat treated factor VIII concentrate, AHF (high purity). AB - Eight batches of a severe dry-heat treated (80 degrees C for 72 hours) Factor VIII concentrate manufactured by the Commonwealth Serum Laboratories (CSL Ltd.) were analysed for the following von Willebrand factor-related (vWf) activities: ristocetin cofactor activity (vWf:RCof), collagen binding activity (CBA), vWf antigen levels (vWf:Ag), vWf multimeric analysis and 2-stage FVIII clotting activity (VIII:C). The average potency per vial of vWf:Ag was 440 +/- 80 units, vWf:RCof 500 +/- 60 units, CBA 350 +/- 50 units and VIII:C 242 +/- 36 International Units. Multimeric analysis indicated the presence of high molecular weight multimers and a triplet structure slightly different to normal plasma. Viral inactivation studies using a marker virus, Sindbis, demonstrated that the terminal severe dry- heating step reduced the viral load in the product by greater than 6 log10TCID50/ml. This CSL Ltd. FVIII concentrate may thus provide a safer, purer and more convenient source of vWf than cryoprecipitate. Clinical studies to establish product efficacy in patients with von Willebrand's disease are underway. PMID- 1631804 TI - A chromogenic enzymatic assay capable of detecting prourokinase-like material in plasma. AB - We report a functional assay capable of quantifying prourokinase (ProUK)- like material in plasma where urokinase (UK) is also present. The assay involves inactivation of urokinase with a specific, active site directed irreversible inhibitor, dansyl-glutamyl glycyl arginine chloromethylketone (dansyl- GGACK). Excess inhibitor is subsequently quenched with dithiothreitol (DTT). The ProUK like material in plasma is then converted to active urokinase with thermolysin, a proteolytic enzyme of bacterial origin. Alpha 2-macroglobulin in plasma inhibits thermolysin; however alpha 2-macroglobulin is inactivated with methylamine. The assay can detect as little as 20 ng of ProUK and is linear from 20 to 120 ng. The assay was applied to quantify the amount of ProUK-like material in plasma obtained from dog at various times after i.v. administration of 100,000 or 75,000 U/kg, of pro-urokinase. PMID- 1631805 TI - K1K2Pu, a recombinant t-PA/u-PA chimera with increased thrombolytic potency, consisting of amino acids 1 to 3 and 87 to 274 of human tissue-type plasminogen activator (t-PA) and amino acids 138 to 411 of human single chain urokinase-type plasminogen activator (scu-PA). Purification in centigram quantities and conditioning for use in man. AB - K1K2Pu, a recombinant t-PA/u-PA chimera with increased thrombolytic potency in animal models of venous and arterial thrombosis, which consists of amino acids 1 to 3 and 87 to 274 of human tissue-type plasminogen activator (t-PA) and amino acids 138 to 411 of human single chain urokinase-type plasminogen activator (scu PA), was produced and conditioned for use in patients. Chinese hamster ovary cells were transfected with an expression plasmid containing the K1K2Pu cDNA, high producer cell lines were selected and scaled up in 800 cm2 roller bottles, and 350 ml conditioned cell culture medium was harvested 3 to 7 times at 2 to 5 day intervals. Batches of 21 +/- 4 liter (mean +/- SD, n = 28) containing 1.8 +/- 0.6 mg/l of K1K2Pu related antigen were purified by chromatography on Copper chelate-Sepharose and immunoadsorption on an insolubilized murine monoclonal antibody (MA-1C8). Yields were 8.6 +/- 3.4 mg K1K2Pu per batch with a specific activity of 83,000 +/- 44,000 IU/mg. The final material, obtained at a concentration of approximately 0.7 mg/ml, was dialyzed against 0.3 M NaCl, 0.02 M Tris-HCl buffer, pH 7.5, containing 0.01% Tween 80 and 10 KIU/ml aprotinin. It was homogeneous on SDS-PAGE, contained 6.5 +/- 6.9 percent two chain material and the contamination with murine monoclonal antibody was less than 0.1 percent. After filtration of pools of 3 to 5 selected batches on 0.22 microns Millipore filters the material was sterile and virus free by routine screening; it was obtained at a concentration of approximately 0.5 mg/ml with a specific activity of 110,000 +/- 16,000 IU/mg (mean +/- SD, n = 3) and an endotoxin content of 0.5 to 7 units/mg. Bolus injection at a dose of 1 mg/kg in mice did not produce weight loss within 8 days. Thus, this material appears to be suitable for the investigation on a pilot scale of the pharmacokinetic and thrombolytic properties of K1K2Pu in patients with thromboembolic disease. PMID- 1631806 TI - Relationship between vitamin K1 2,3-epoxide and vitamin K1 in patients treated with N-methyl-thiotetrazole cephalosporins. PMID- 1631807 TI - Platelet serotonin content and microcirculation haemostasis in spontaneous arterial hypertension in rats. PMID- 1631809 TI - [Sudden infant death and sleeping position]. PMID- 1631808 TI - Coupled D dimer and fibrinogen levels during thrombolytic therapy of venous thromboembolism. PMID- 1631810 TI - [Medical records--both about patients and for patients]. PMID- 1631811 TI - [Invasive treatment of coronary diseases]. PMID- 1631812 TI - [Sleeping position and crib death in Norway]. AB - Questionnaires to maternity hospitals in Norway in 1989 and 1991 showed that most units had changed the babies' sleeping position from the side position in the early 1970s, to predominantly prone in 1989, but back to the side position between 1989 and 1991. Parallel with these changes the incidence of sudden infant death increased steadily from 0.93 per 1,000 live births in the early 1970-74 to 2.4 per 1,000 in 1989, and dropped dramatically to 1.4 per 1,000 in 1990. It is assumed that parents adopt the sleeping position preferred in the maternity ward, and the study therefore supports the theory that the prone position significantly increases the risk of sudden infant death. PMID- 1631813 TI - [Coronary artery stenting. A new therapeutic alternative in Norway]. AB - In Norway the first percutaneously, transluminally placed human coronary artery endoprosthesis (stent) was implanted in the spring of 1991. This article summarizes international experience of treatment with the Palmaz-Schatz balloon expandable stent for coronary use and describes the first two patients treated with such implants at Ulleval hospital. PMID- 1631814 TI - [Angina pectoris after coronary angioplasty. Restenosis or partial revascularization]. AB - Percutaneous transluminal coronary angioplasty (PTCA) was performed on 115 consecutive patients with angina pectoris and the results were evaluated after an average of 100 days by means of bicycle exercise test and coronary angiography. Complete revascularization was achieved in 75% of the patients. Restenosis occurred in 23%. A good symptomatic effect was found in 90% of the patients with complete revascularization and in 72% of the patients with partial revascularization. Recurrence of angina pectoris 4-8 weeks after PTCA is a predictor of restenosis. Absence of angina and a negative bicycle exercise test 3 4 months after PTCA are strong predictors of the absence of restenosis. PMID- 1631815 TI - [Intermittent bradyarrhythmia in infants and small children treated with permanent pacemaker]. AB - Four children aged two, two and four months and five years respectively, with intermittent cardiac bradyarrhythmias and otherwise normal hearts are described. The diagnoses were based upon findings by telemetry and 24-hour ECG-recordings. Two patients had sinus node disease, one patient had intermittent complete atrioventricular block, and the fourth had a permanent first degree atrioventricular block and intermittent high grade second degree atrioventricular block. All patients presented serious symptoms with apparent life-threatening events before admission. They were given a permanent cardiac pacemaker. One patient experienced recurrent excessive increase in the myocardial stimulation threshold, leading to further syncopal episodes. All patients are developing adequately with normally functioning pacemakers. PMID- 1631816 TI - [Development and use of a database for gastroenterologic endoscopy]. AB - With no commercially available endoscopy database manager available, a standalone system for gastroenterological endoscopy departments has been developed since 1985 through joint efforts of gastroenterologists and dedicated programmers. The present system was implemented for daily use January 1989 and, to date, approximately 19,000 examinations have been recorded. Nurses and office assistants carry out administrative work, but the physician enters the endoscopic data, partly as free text, partly as structured data via automated menus and a mouse. In addition to the immediate printout of the result, valuable data are stored in the computer for administrative and research purposes. Mean data entering time for the physician was four minutes 17 seconds, and altogether eight minutes 40 seconds was spent on the computer system for each patient served. PMID- 1631817 TI - [Primary HIV-infection. A differential diagnosis of mononucleosis/influenza-like symptoms]. AB - We describe the history of a 29 year-old heterosexual female who presented symptoms and signs similar to those indicating infectious mononucleosis and influenza. However, the diagnosis turned out to be a primary HIV infection. The patient is highly infective at this phase of the HIV disease, and this report emphasizes the importance for general practitioners to have this diagnosis in mind when treating patients with "sero-negative" mononucleosis or influenza-like symptoms. The HIV-infection was suspected earlier but not confirmed until five weeks after the first positive screening test was taken. This illustrates the importance of repeated HIV testing when primary HIV infection is suspected. PMID- 1631818 TI - [Synovial chondromatosis]. AB - Synovial chondromatosis is a rare monarticular condition in which cartilaginous masses are formed by metaplasia of the synovial membrane. These masses may calcify and ossify. The disease most commonly affects the knee, and the symptoms include pain, swelling, locking and palpable loose bodies. Although the clinical features are usually non-specific, the roentgenograms often provide important diagnostic information. Synovial chondromatosis is rarely a difficult diagnostic problem, but should not be confused with other disorders that give rise to loose bodies, such as degenerative joint disease and osteochondritis dissecans. Two cases are described and synovial chondromatosis is discussed in some detail, including radiological features and treatment. PMID- 1631819 TI - [Perinatal listeriosis]. AB - Human listeriosis is a rare disease. It may be foodborne. Listeric infection during pregnancy may give a fatal fetal outcome, caused by transplacental passage of organisms from the maternal gastrointestinal tract. We describe a case of perinatal listeriosis which resulted in preterm stillbirth. Perinatal listeriosis should be considered when flue-like symptoms are presented during pregnancy. Early diagnosis and treatment may improve the outcome. PMID- 1631820 TI - [Acute pancreatitis after treatment with sulindac]. AB - Two women, aged 91 and 46 years respectively, developed acute pancreatitis following treatment with sulindac (Clinoril) for five weeks in the one case and four and a half years in the other. The oldest patient became acutely ill. An emergency laparotomy was performed which showed considerable pancreatic edema and typical fat necroses. The other case presented a more protracted course and was not operated. Restitution was remarkably quick in both patients after cessation of the sulindac treatment. PMID- 1631822 TI - [Multiple injuries in children]. AB - Multiple injuries do not occur very often in children, but are important because children's general reaction to trauma is different from that of adults. This is due to the anatomic and physiological differences between children and adults, and because some injuries in children differ considerably from similar injuries in adults. It is important to know these facts, even if the methods used for resuscitation and immediate follow-up are much the same in children as in adults. A special type of injury that is seen with increasing frequency comprises the bizarre injuries caused by child abuse. PMID- 1631821 TI - [Multiple injuries in pregnant women]. AB - It is relatively uncommon for pregnant women to suffer multiple injuries. In such a situation, however, two lives are at stake. The survival of the foetus depends on the mother's condition with regard to respiratory passage, oxygenation, and hypovolemia. This last condition implies that the blood is shunted away from the uteroplacental circulation, thus endangering the foetus. The principles of treatment are the ones described in this series of articles, and furthermore, in addition to concern for the foetus. Blows against the abdomen can cause abruption of the placenta, which is a frequent cause of death of the foetus after closed trauma, and can occur up to 48 hours after the accident. This necessitates monitoring of the foetus during this period. PMID- 1631823 TI - [Light therapy of newborns with hyperbilirubinemia]. AB - In a significant fraction of newborns the skin becomes yellow for a few days after birth due to accumulation of bilirubin, a product of heme catabolism. If the concentration of bilirubin in the serum approaches the binding capacity of albumin, bilirubin may penetrate into the central nervous system and cause irreversible damage. Phototherapy is the most common form of therapy, used on 5 10% of all newborns in Norway. Three photochemical reactions are of importance in this treatment: Photooxydation of bilirubin followed by fragmentation of the molecule and formation of water-soluble products. Reversible formation of (4Z,15E) and (less important) (4E,15Z) configurational isomers. Irreversible formation of the structure isomer Z-lumirubin, which is relatively water-soluble and can be excreted. The (4E,15Z) isomer is probably an intermediate in the formation of Z-lumirubin, whose formation therefore requires the absorption of two photons. Irreversible formation of Z-lumirubin, which has a quantum yield that increases with increasing wavelength of the light, is believed to be the most important reaction in phototherapy. All known side-effects of phototherapy are transient and not serious. PMID- 1631824 TI - [Technique for taking specimens for cervical and endometrial cytological tests]. PMID- 1631825 TI - [Crib death, sleeping position and temperature]. AB - Sudden infant death syndrome (SIDS) is the commonest cause of death in children over one week of age. Norway has the highest incidence in Scandinavia and the figure has increased during the last 20 years. There has been much discussion as to whether sleeping in the prone position rather than in the supine or lateral position may be a predisposing factor to cot death. In all 14 studies in seven countries where the question has been investigated, there was a higher proportion of prone infants in the SIDS group than in the control group. Intervention studies have shown that reducing the proportion of infants sleeping prone was followed by a reduction in cot deaths. There is also evidence that overheating is a risk factor for SIDS. In one British study it was found that infants who died of SIDS had more clothes on, and blankets covering them, and that both prone position and overheating were independently associated with SIDS. A possible mechanism is that overheating interferes with respiratory control. Although we do not completely understand the mechanisms underlying the links between SIDS and the prone position, the epidemiological evidence and the evidence from intervention are now so strong that it is fully justified to advice against the general use of the prone sleeping position for babies. PMID- 1631826 TI - [Patients' diary--a useful communication tool for both patients and health personnel]. AB - Elderly people living at home and suffering from one or more chronic diseases often receive help from different sectors of the public health service. Good communication between these different health workers is often lacking. To improve this situation we are now using a supplementary journal which is kept in the patient's own possession and brought with him or her to hospital and consultations. We have tried out this method for two years, have found it very useful, and shall continue to use it permanently. We hope this article will serve to acquaint doctors with this journal. We also discuss our experiences after having started to use the journal. PMID- 1631827 TI - [Microcomputer-based medical records system for diseases of the female breast]. AB - We describe a microcomputer-based Medical Record for diseases of the female mammary gland. The system is based on multiple-choice questionnaires used by the physician and later transferred to the computer. The computer produces written output for transfer to the patient record. Statistical information can be obtained through preprogrammed menus. The system has been used as the only documentation for the patient group at the Surgical Department, Ullevaal Hospital for more than four years. We discuss system design, statistical results and future development. PMID- 1631828 TI - [Smoking and extrauterine pregnancy]. AB - During the last twenty years the incidence of ectopic pregnancies has doubled or tripled. They constitute about 1.13% of all pregnancies in Norway, and remain an important cause of subsequent infertility. The main risk factors are sexually transmitted diseases, pelvic inflammatory disease, and use of intrauterine device. This paper reviews some of the recently published epidemiologic and non epidemiologic reports that have shown a positive association between ectopic pregnancies and cigarette smoking. Some ectopic pregnancies would probably be prevented if pregnant women refrained from smoking. PMID- 1631829 TI - [Medical advisers and chief physicians at Norwegian somatic hospitals]. PMID- 1631830 TI - [Delivery on the mother's or the infant's premises?]. AB - A delivery should take place on the infant's premises. The mother's wishes and needs should also be taken into consideration, however, as long as they do not involve hazard to the child. The mother should have the right to take leave of absence at least four weeks before term and approximately one year after delivery. ABC-principles (Alternative Birth Care) during pregnancy and labour could be applied by making a hospital delivery more like a home delivery. PMID- 1631831 TI - [Methadone therapy--for whom?]. PMID- 1631833 TI - [Incidence of scalp problems among soldiers in Sessvollmoen]. PMID- 1631832 TI - [Health problems of women-- accidental falls and injuries?]. PMID- 1631835 TI - [Criteria of suitability for medical education]. PMID- 1631834 TI - [Child ombudsman, health centers and family practice]. PMID- 1631836 TI - [On the concept of cause]. PMID- 1631837 TI - [Doubt about atenolol in the treatment of hypertension]. PMID- 1631838 TI - [Cholera]. PMID- 1631839 TI - [The age of internationalism. We live in the age of internationalism and the Norwegian physicians and their Society must adapt to it]. PMID- 1631840 TI - [Late diagnosis of advanced breast cancer--a challenge for health services]. AB - From 1982 to 1987, 1,637 cancers of the breast were diagnosed in Oslo. 235 were classified as advanced according to one or more of the following criteria: tumour size greater than or equal to 5 cm (T3) or T4, metastasis within 4 months, pathological diagnosis pT3, pT4 or pN2. These were further studied. The distribution of women with advanced cancer mammae was uneven. For no obvious reason, incidence was significantly higher in one out of four hospitals in Oslo. 169 of the patients discovered the tumour themselves. Many patients delayed seeking help. 93 waited for more than eight weeks before doing so. For patients with metastasis at time of diagnosis, survival was slightly more than one year, and for patients without metastasis it was four and a half year. The length of stay in hospital increased with increasing admissions. PMID- 1631841 TI - [Ultrasonography for early diagnosis of abdominal aortic aneurysm]. AB - 2,654 males aged 60 years or older were invited to attend a screening examination using ultrasound to detect abdominal aortic aneurysm. 1,256 met up. A fee of NOK 150 was charged. 92 aneurysms were detected (7.3%) 69 were smaller than 40 mm and 23 were 40 mm or larger. During the observation period (18 months from start of the study and nine months after screening stopped) 17 of the patients with an abdominal aortic aneurysm of 40 mm or larger had elective operations. All patients survived without major complications. Owing to the high prevalence of abdominal aortic aneurysm, the low cost of screening, and the safety of elective surgery, it is suggested that screening for detection of abdominal aortic aneurysm should be carried out on a larger scale. PMID- 1631842 TI - [Ischemic hepatitis. Important differential diagnosis of increased levels of transaminases in the liver]. AB - In patients with pathological findings in tests of liver function, ischemic hepatitis is an important differential diagnosis. This condition is most often seen in patients with coronary heart disease. Acute circulatory failure may induce reduced liver perfusion with extreme elevation in transaminase levels within three to five days. The values return to normal within five to ten days and in uncomplicated cases there is minimal cholestasis. Ischemic hepatitis may progress to fulminant hepatic failure. The diagnosis can be made by clinical examination and biochemical tests alone. Biopsy gives a characteristic picture of centrilobular liver cell necrosis which confirms the diagnosis, but is seldom necessary. PMID- 1631843 TI - [Systemic lupus erythematosus and pregnancy]. AB - In patients with systemic lupus erythematosus in remission pregnancy has a good prognosis for mother and foetus. Pregnancy does not have a negative effect on systemic lupus erythematosus in remission, either in the short or the long term. Immuno-regulatory drugs should not be withdrawn before or after start of pregnancy, and flares during pregnancy can be treated with steroids and/or azathioprine. The risk of flare is very high in the puerperium, and can be prevented by steroids. All patients are at high risk of losing the foetus, particularly patients with antiphospholipid antibodies. Patients at high risk should be given low doses of aspirin (80 mg daily) from the first day of pregnancy. Neonatal lupus and congenital heart block are rare, and are associated with the presence of anti-SSA and anti-SSB antibodies in the maternal blood. PMID- 1631844 TI - [Tissue expansion]. AB - Tissue expansion has now achieved an important place in reconstructive surgery, since the first experiments about 10-15 years ago. Expanded tissue used in reconstruction is usually excellently matched for colour, thickness, elasticity and other physical properties. This is particularly important in reconstructions in the head and neck region. Tissue expansion is also used increasingly for breast reconstruction all over the world. It is now the most common procedure for breast reconstruction in USA. Various options using either a temporary or a permanent expander are discussed. PMID- 1631845 TI - [Evaluation of suicidal tendency]. PMID- 1631846 TI - [The cholera epidemic in Latin America]. AB - An outbreak of cholera started in Peru in January 1991 and spread through most Latin American countries within a year. This was the first known epidemic of cholera in America for more than a century. In 1991, 321,334 persons were reported to have cholera in Peru, 119,063 were hospitalized, and 2,906 died. Other countries like Ecuador, Colombia, Guatemala, Brazil, Mexico, Bolivia, Chile, El Salvador, Venezuela and Honduras were also affected, but these countries combined accounted for only 20% of the cases registered in Peru. In April 1992, all Latin American countries except Uruguay, Paraguay and French Guyana have reported cholera. The mortality rate for the epidemic in Latin America was only 1%, mainly owing to good oral rehydration treatment provided by Local health services and the Pan American Health Organization. The causative organism was Vibrio cholerae, serogroup O1, serotype Inaba (and Ogawa) of the El Tor biotype. Genetic characterization shows this strain to be unique, and the designation is reserved for the Latin American strain, distinguishing it from the other El Tor isolates from the 7th pandemic. PMID- 1631847 TI - [Occupational anamnesis in general practice. Does it yield useful information for preventive procedures?]. AB - To what extent can general practitioners elucidate connections between working conditions and patterns of health and disease for preventive purposes? Data were collected by means of questionnaires to general practitioners, interviews with patients and by testing out questions to establish an occupational history. Questions covering seven key topics revealed a multitude of possible causal links between working conditions and symptoms. The information may appear irrelevant to the general practitioner, however, if the Labour Inspection (Arbeidstilsynet) or the companies' health services fail to assist. PMID- 1631848 TI - [Leadership and professionalism]. AB - In 1990 a new organizational structure based on decentralization and team leadership, where the leader (usually a doctor) is responsible for the final decision, was introduced at the regional and university hospital of Tromso. This structure replaces the traditional dual structure of leadership where the leaders (a doctor and a nurse) did not share responsibility for the whole department. In order to analyze organizational practices after the reform we constructed three different organization models of the hospital: the hierarchical model, the professional model and the workshop model. Of five teams, one functioned hierarchically, three resembled the professional model, and the fifth came close to the workshop model. The leader of the hierarchical team behaves autocratically and the employees are dissatisfied. In the three remaining teams conditions have changed very little compared with the situation before the reorganization. In the workshop team decisions are reached jointly. This team functions in an innovative way. Even though the new organizational structure has quite divergent consequences and some leaders have problems, the majority of the hospital employees support the new structure. PMID- 1631849 TI - [Introduction of quality assurance systems for medical technical equipment]. PMID- 1631850 TI - [Quality assurance--where is the challenge?]. PMID- 1631851 TI - [Diagnosis-related groups--possibilities and problems]. PMID- 1631852 TI - [Silicone breast prostheses--a guideline or misinformation from the Helsedirektoratet (Office of Health Authority)]. PMID- 1631853 TI - [Methadone treatment--for whom?]. PMID- 1631854 TI - [Hyperkalemia--repeat potassium determination in heparin plasma]. PMID- 1631855 TI - [Natural products can be hazardous to health]. PMID- 1631856 TI - [Elderly physicians are discriminated against]. PMID- 1631857 TI - [Habilitation/rehabilitation--young people and adults with congenital or early acquired functional disabilities]. PMID- 1631858 TI - [The medical doctor degree under revision]. PMID- 1631859 TI - [How can we improve hospital quality? Can hospitals learn anything from industry?]. PMID- 1631860 TI - Forgotten pioneers in thoracic surgery. AB - The names of Carrel, Sauerbruch and Blalock are milestones in the early history of thoracic surgery. The recognition of contributions by less renowned contemporaries does not diminish the decisive part played by these founders of prestigious schools of thoracic surgery. Kronlein who in 1883 successfully performed what was probably the first lobectomy is never mentioned. The esophagectomy without thoracotomy publicized by Orringer in 1978 had already been done by Gray-Turner 47 years before, in 1931. McLean who discovered heparin, and Forssmann who introduced cardiac catheterisation by passing an ureteral catheter into his own heart ended up as small-town general surgeons. Horace Smithy of Charleston successfully performed an operation for mitral stenosis four months before Bailey and Harken. Unlike his famous contemporaries, he was unable to publicize his cases at medical meetings because that same year, 1948, he died from an aortic vascular stenosis. Vineberg, who had recommended and successfully performed internal mammary artery implantation since 1946, was smiled at as a utopian until his rehabilitation by Mason Sones' coronarography and until coronary bypass surgery developed into the greatest boom in thoracic surgery. Sir Henry Souttar, who is known to have operated successfully a mitral stenosis a quarter of a century before Bailey, when asked why following his 1925 success he did not persue mitral surgery answered: "Because I could not get another case!" As usual, surgical "break-throughs" met with the resistance of medical men. Before doctors became enthusiastic advocates and referred thousands of cases of pulmonary tuberculosis, and mitral and coronary stenosis, their opposition had to be overcome by successful operation of generally desperate cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1631861 TI - Biochemical and functional effects of creatine phosphate in cardioplegic solution during aortic valve surgery--a clinical study. AB - During myocardial ischemia there is a drop in high-energy phosphates in the myocardium. Cold potassium cardioplegia decreases but does not altogether prevent this reduction. Supplementation of cardioplegic solutions with the high-energy compound creatine phosphate (10 mmol/L) compared to plain cardioplegic solutions was investigated in this study. Thirty patients scheduled for aortic valve replacement were included. The patients were randomized to group I (creatine phosphate) or group II (control). Postoperative hemodynamic evaluation revealed no significant differences between the groups. However, group I exhibited a tendency toward a better stroke-work index (135 +/- 18% vs. 102 +/- 5% recovery 15 minutes after bypass and 145 +/- 16% vs. 119 +/- 11% recovery 105 min after bypass). There were fewer patients in group I (5/15) needing inotropic support compared to group II (9/14). The myocardial content of ATP and creatine phosphate showed no significant differences during ischemia and reperfusion. It is concluded that the myocardial protection during ischemia was sufficient to prevent significant reductions of myocardial ATP and creatine phosphate irrespective of supplementation with CP. PMID- 1631862 TI - New surgical techniques for the prevention of paraplegia during aortic surgery. AB - It has been shown in previous publications that ischemic spinal cord injury after aortic cross-clamping may be produced by a steal-phenomenon. The present study investigates this phenomenon and the direction of spinal cord blood flow by directly measuring the oxygen tension on the spinal cord surface in pigs. After simple clamping of the aorta, oxygen tension decreased significantly distal to the clamping site both after occlusion of the thoracic aorta at T3-4 (group I) and the abdominal aorta at L1 (group II). Exclusion of the thoracic aorta by second clamping at T 13 restored oxygen tension almost to the control level while segmentation of the abdominal aorta up to S1 hardly affected oxygen tension in the area of the Adamkiewicz artery in most animals. An additional occlusion of the spinal cord proximal to the measuring point did not lead to a significant alteration of oxygen tension. It is concluded that, after aortic cross-clamping, blood tends to drain away from the spinal cord rather than supply it longitudinally. A steal phenomenon always has to be taken into account if any radicular artery, especially the artery of Adamkiewicz, supplies the spinal cord distal to the clamping. Without cognizance of the position of the Adamkiewicz artery in man as well as of the competence of the collateral circulation in the excluded segment, a new additional strategy needs to be developed for repair of the aorta. Two surgical techniques for the prevention of paraplegia after aortic cross-clamping are described and discussed: the counter occlusion technique and the bypass fractionated technique. PMID- 1631863 TI - First clinical experiences with a new angioscopic system for diagnosing peripheral vascular changes. AB - Conventional angiography allows a global view of regional vascular anatomy but precise information can only be deduced indirectly using contrast medium. The use of the three-dimensional picture of angioscopy, however, allows a direct evaluation of the vascular system. In order to extend our experiences with angioscopy, we employed a new micro-cardio-angioscopic system which consists of four components: a CCD color camera (360,000 pixels); a highly flexible optical probe which can be resterilised (1.4-0.6 mm diameter) incorporating 10,600-6,000 glass fibers, with a viewing angle of 140 degrees, 70 degrees, and 50 degrees and a focusing system that allows a distance from 2 mm to infinity; a high power light source and an insertion catheter with inflatable balloon. Using a known technique (intermittent blood-flow blockage and continual rinsing with NaCl solution), 36 cases involving 27 patients were examined before and after desobliteration of the femoral artery. In 88% of the cases it was possible to control the result of the intervention by angioscopy. Smaller intimal lips, the thrombotic wall, and intimal ruptures were clearly visible. Quantification of the stenoses was also successful in 88% of the cases, and in 8 patients the angioscopic findings deviated from the conventional angiogram. In 14% of the cases, angioscopic examination of the recanalisation result showed that thrombolytic therapy was necessary. Angioscopy offers the possibility of qualitative vascular diagnosis. It is a valuable addition to angiography. PMID- 1631864 TI - A new vascular prosthesis of bovine origin. AB - An experimental study on a new biologic vascular graft for reconstruction of small diameter arteries was carried out in 50 sheep. A follow-up period of two years let us conclude that the new vascular prosthesis may be "re-utilized" by the host. Infection and aneurysmatic degeneration could not be observed. An early occlusion of the graft occurred in only one case, due to technical reasons. PMID- 1631865 TI - Echinococcal cyst of the interventricular septum: a rare cause of myocardial ischemia. AB - A 30-year-old woman developed ischemia-like chest pain due to myocardial compression by an intracardiac cyst. The cyst was located in the interventricular septum. Its etiology could not be ascertained despite several diagnostic measures but exstirpation was indicated by the clinical symptoms. Intraoperatively the diagnosis of echinococcosis was established. The cyst was extirpated in toto without perforation of the thinned interventricular septum. Postoperatively the patient was symptomfree. PMID- 1631866 TI - Aorto-cutaneous fistula: a rare complication of aortic surgery. AB - Two cases of false aneurysm of the ascending aorta which presented with discharge of arterial blood from a sternal wound are discussed. The first presented 8 years after aortic valve surgery and was diagnosed by contrast enhanced computerised tomography of the thorax. The second presented 6 months following repair of an aortic dissection and the diagnosis was confirmed by thoracic magnetic resonance imaging. The diagnosis and surgical management of these cases are reviewed. PMID- 1631867 TI - Leiomyosarcoma of the pulmonary hilar vessels. AB - Leiomyosarcomas are uncommon tumors. They have a predilection for deep soft tissues, with a rare group arising in medium-sized or large veins, far less frequently in arteries. We report a case of a 63-year-old man, with an enlarging mass located in the left pulmonary hilar region which was discovered on a routine chest radiograph. Cytology of the sputum and bronchoscopic biopsies did not reveal any malignant cells. Over 5 months observation, there was a clear progression of the mass, and the patient finally underwent a left pneumonectomy which allowed the diagnosis of an intravascular leiomyosarcoma partially destroying major arteries and veins in the hilar region. A review of the literature reveals 67 cases of leiomyosarcoma involving the pulmonary artery. None of these cases had an associated venous pathology. The disease is found mainly in adult women. Clinical diagnosis is very difficult because most of the cases have no specific clinical signs; the major differential diagnosis is that of pulmonary thrombo-embolism. Prognosis depends on histological degree of the tumor and extent of the disease, metastases occur mainly in the liver, lung, and brain and less frequently in regional lymph nodes. Treatment is always surgical, chemotherapy is ineffective and the effectiveness of radiotherapy depends on the total dose of irradiation. Sarcomas of hilar blood vessels have a very poor prognosis with a one year survival estimated, from the onset of symptoms, at 20%. PMID- 1631868 TI - Treatment of intractable ventricular fibrillation with prompt circulatory support using a biventricular assist device in pigs--an experimental study. AB - Refractory ventricular fibrillation (VF), intractable to conventional therapy, can be converted into a stable cardiac rhythm by immediate ventricular volume unloading using a form of mechanical circulatory assist (MCA). We investigated the efficacy of MCA in a controlled animal study in which 20 pigs were subjected to intermittent occlusions (5 times) of the left descending coronary artery (5 min. occlusion + 10 min. reperfusion). 12 of the 20 animals (60%) developed 14 events of VF. 64% of VF developed during reperfusion (p less than 0.05). Countershock was attempted up to eight times and was successful in 5 of the 14 events (36%) (primary defibrillation, PD). When conversion was not achieved, total biventricular bypass was instituted. Mean perfusion time between countershock attempts was 24.4 +/- 15.3 min. All animals (n = 9) with cardiac assistance were successfully defibrillated (secondary defibrillation, SD), (p less than 0.05). Hemodynamic parameters after SD were not significantly different from those after PD (p greater than 0.05). Survival rate following PD was 66.6%. Six animals were ultimately weaned from cardiac assistance following SD. Three others died of progressive cardiogenic shock in the six hour follow-up period following SD. These non-survivors had a significantly longer VF time than the survivors (41.7 +/- 10.4 vs. 15.8 +/- 8.0, p less than 0.05). Overall survival after SD was the same as that for PD: 66.6% (p greater than 0.05). These results show that prompt conversion of VF into a stable cardiac rhythm is a prerequisite to recovery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1631869 TI - Omental pedicle flap used to treat a bronchopleural fistula after diaphragma pericardio-pleuropneumonectomy. PMID- 1631870 TI - Renal cell carcinoma extending into the right ventricle: successful resection with cardiopulmonary bypass. AB - Successful total removal of a renal cell carcinoma extending through the tricuspid valve into the right ventricle is reported. The rarity of this case prompted a review of the literature in which only right atrium involvement in this type of tumor was found. PMID- 1631871 TI - Partial "anomalous" hepatic venous connection associated with secundum atrial septal defect. AB - Postnatal connection of hepatic veins with the coronary sinus represents the rare persistence of a normal early embryonic development. A case is presented where this was found intraoperatively, associated with a secundum type atrial septal defect. Knowledge of this anatomic variation and its specific features may facilitate preoperative diagnosis, thereby preventing surprises in the operating room. PMID- 1631872 TI - Protection of a transplanted kidney during aortoiliac reconstruction. PMID- 1631874 TI - Comparison of myectomy alone or in combination with mitral valve repair for hypertrophic obstructive cardiomyopathy. AB - Between 1/84 and 6/91 56 patients were treated for hypertrophic obstructive cardiomyopathy (HOCM): the Morrow technique alone was performed on 40 patients (group 1), in 16 patients (group 2) an additional replacement (n = 13) or reconstruction (n = 3) of the mitral valve was indicated. In a total of 14 cases coronary artery bypass grafting and aortic valve replacement was performed in addition. Postoperatively (mean follow-up 4.2 yrs, 141 patient-years) left ventricular diastolic and systolic function parameters, heart muscle mass, ECG findings, and symptomatology were recorded and the ratios of beta-adrenoreceptor density to density of the calcium channel were measured. RESULTS: Pressure gradient decreased from 69.2 +/- 5.2 (group 1) and 75.1 +/- 4.8 (group 2) to 23.3 +/- 2.7 and 11.7 +/- 2.2 mmHg postoperatively. Likewise Sokolow-Lyon index decreased from 3.5 +/- 0.2/3.7 +/- 0.2 to 2.9 +/- 0.2/2.8 +/- 0.3. The quotient time-to-peak-velocity/left-ventricular-ejection-time decreased significantly in group 2 from 58.6 +/- 6.3 to 41.9 +/- 5.8 (p less than 0.05). The heart muscle mass, determined echocardiographically, decreased from 680g to 430g (p less than 0.05). Isovolumetric tension time, isovolumetric relaxation time, and E/A ratio at rest and after stress showed typical characteristics. Ca(++)-channel density was clearly raised in all patients, with no differences between the two groups being observable. We conclude from our results: The most marked improvements in clinical and left-ventricular functional parameters were experienced by patients in group 2 (myectomy+MVR).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1631873 TI - Preoperative and late postoperative psychosocial state following coronary artery bypass surgery. AB - In a prospective study of psychological and neurological reactions to coronary artery bypass surgery, 45 patients were examined preoperatively, postoperatively, and 21 to 27 months after, using a variety of neurological, psychiatric, and psychological investigations. Within the follow-up sample, three subgroups of patients could be identified by cluster analysis who differed with respect to their emotional status and life satisfaction. One group (24% of the total sample) was characterized by high levels of anxiety, depression and life dissatisfaction and appears as a risk population. The other groups could be described as either average (42%) or stable (33%). At the follow up, the risk group further indicated a preference for depressive coping styles, a slightly higher degree of cognitive impairment, more neurological and psychopathological symptoms (specifically giving-up and hostility), a considerably lower return-to-work rate, more subjective physical complaints and a poorer attitude toward the outcome. While postoperative measurements (obtained 2-3 and 6-8 days after surgery) as well as intraoperative parameters did not reveal significant group differences, the analysis yielded an increased impairment within the risk group already prior to surgery, especially emotional problems, specific health-related cognitions and a more fatalistic attitude. The results are in line with those of other studies investigating the late postoperative psychological status with regard to the proportion of patients showing psychological impairments as well as to their specific psychological characteristics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1631875 TI - Relationship of atrial fibrillation to significant pericardial effusion in valve replacement patients. AB - Rhythm change was observed in 21 of 242 (8.7%) patients during the first four weeks of open heart surgery (OHS). In the valve-replacement group of 148 patients the rhythm change was found to be associated with significant pericardial effusion (PE). Seven patients had rhythm changes during the first three days of OHS unrelated to PE. Two patients who were in atrial fibrillation (AF) developed fast ventricular rate and twelve patients showed rhythm change from sinus to supraventricular tachyarrhythmia (AF in ten and supraventricular tachycardia in two) and all these fourteen patients had significant PE. With pericardiocentesis or open drainage or withdrawal of anticoagulation, AF reverted to sinus rhythm in nine patients and five patients remained in AF but with a slow ventricular rate. Significant PE was related to a high anticoagulation ratio. We conclude from this study that within the first four weeks of OHS, high anticoagulation ratio contributes to the development of significant PE, and tachyarrhythmia (particularly AF) is a forerunner of significant PE or cardiac tamponade: the aim of management should be to rule out or show evidence of significant PE once tachyarrhythmia develops, and if significant PE is present then the pressure in the pericardial cavity should be reduced. PMID- 1631876 TI - The effects of systemic intraoperative hypothermia on the acute-phase and endocrine response to cardiac surgery. AB - To determine the ability of intraoperative hypothermia to modify changes in the plasma protein component of the acute-phase response (APR) and the plasma hormone component of the endocrine response (ER) to surgical injury, 20 patients undergoing coronary artery surgery were randomised to an intraoperative blood temperature of 28 degrees C or 20 degrees C during cardiopulmonary bypass (CPB). Serial measurements of pack-cell-volume corrected concentrations (PCVCC) of five plasma proteins (albumin, prealbumin, transferrin, caeruloplasmin, ferritin) and six plasma hormones (adrenaline, noradrenaline, cortisol, triiodothyronine, thyroxine, and thyroid-stimulating hormone) were obtained twice preoperatively, seven times during surgery, six times in the 24 hours following surgery, and a further four times until the seventh postoperative day. A more profound level of intraoperative hypothermia significantly reduced the plasma adrenaline response to CPB but not the other components of the ER or APR. PMID- 1631877 TI - Modified preservation of all annular-papillary continuity in replacement of the calcified mitral valve. AB - The technique described here is a modification of the mitral valve replacement with preservation of chordae tendineae for calcified mitral stenosis. After commissurotomy, the middle portion of the anterior leaflet is excised to get two parts with accessible chordal insertion. Each thickened and calcified segment is debrided by means of an ultrasonic tool and then attached to the mural leaflet. Finally mitral valve replacement is carried out. This procedure will extend surgical indication of chordae-sparing methods in mitral valve replacement for mitral stenosis. PMID- 1631878 TI - Pain relief and respiratory mechanics during continuous intrapleural bupivacaine administration after thoracotomy. AB - Continuous intrapleural bupivacaine administration was assessed in a randomized double-blind manner with respect to its analgesic effect and its impact on breathing after thoracotomy. The pleural cavity was infused continuously for 48 hours in 24 patients following thoracotomy for pulmonary resection. 12 patients received 10 ml/h of bupivacaine hydrochloride 0.5% solution, and 12 patients 10 ml/h NaCl 0.9% solution. There were no differences in the patients' characteristics, extent of surgery, mode and duration of general anaesthesia. There were no complications related either to the catheter or to bupivacaine. The amount of postoperative opioid, given on request, was used to assess the effect of bupivacaine administration on pain relief. Post-thoracotomy breathing was assessed by measuring the forced vital capacity (VC) prior to and after physiotherapy. The VC values measured 24 h, 36 h and 48 h after the operation were similar in both groups of patients with or without bupivacaine administration (p greater than 0.05). Patients given bupivacaine required significantly less opioid analgesia than those who received NaCl 0.9% at 24 h (p less than 0.001), 36 h (p less than 0.001) and 48 h (p less than 0.01) after the operation. Continuous intrapleural bupivacaine analgesia through a paravertebral catheter positioned in the paravertebral groove is safe and provides efficient pain relief after thoracotomy. PMID- 1631879 TI - Primary mucoepidermoid carcinoma of the thymus--a rare cause of mediastinal tumour. AB - We present a primary mucoepidermoid carcinoma of the thymus which is an extremely rare cause of mediastinal tumour. Growth is slow with cure obtained after complete resection. Only two previous cases have been reported. PMID- 1631880 TI - Truncus arteriosus communis associated with interrupted aortic arch: a report on two uncommon cases. AB - The paper presents two infants with the A-4 type of truncus arteriosus communis (according to Van Praagh's classification). One patient who survived a surgical procedure demonstrated a rare variant of aortic arch interruption to the left off the left subclavian artery (type A according to Celoria and Patton), whereas the second presented an uncommon anomaly in which the right subclavian artery originated from the descending aorta with associated severe truncal valve incompetency. The authors describe the clinical picture along with the surgical treatment of the first infant who being six days old was subjected to a correction employing the wide patent ductus arteriosus to reconstruct the aortic arch, following the method described by Gomes and McGoon. Subsequently an aortic homograft was implanted in order to connect the right ventricle and the pulmonary artery. PMID- 1631881 TI - Replacement of a thrombosed St. Jude Medical prosthesis in pulmonary position after repeated thrombolytic therapy. AB - A 49-year-old man who had undergone repair of tetralogy of Fallot underwent replacement of a thrombosed St. Jude Medical prosthesis in pulmonary position after intravenous thrombolytic therapy. Dysfunction of the prosthetic valve was detected clinically by change of heart sound and the appearance of a new diastolic murmur. Cinefluoroscopy confirmed fixation of both leaflets. Although thrombolytic therapy using urokinase was successful twice, the prosthesis was replaced with a Carpentier-Edwards bioprosthesis due to recurrent prosthetic dysfunction. PMID- 1631882 TI - Introduction to multihospital systems. PMID- 1631883 TI - The evolution of Catholic multiinstitutional systems. PMID- 1631884 TI - The future of multihospital systems. PMID- 1631885 TI - When the system can't save the hospital: a practical overview of workouts and bankruptcy alternatives. PMID- 1631886 TI - Financial and operating performance of systems: voluntary versus investor-owned. PMID- 1631887 TI - Mn2+ sequestration by mitochondria and inhibition of oxidative phosphorylation. AB - Manganese is known to accumulate in mitochondria and in mitochondria-rich tissues in vivo. Although Ca2+ enhances mitochondrial Mn2+ uptake, ATP-bound Mn2+ is not sequestered by suspended rat brain mitochondria, and ATP binds Mn2+ even more tightly than it binds Mg2+. Physiological levels of the polyamine spermine enhanced 54 Mn2+ uptake at the low [Ca2+]s characteristic of unstimulated cells (approximately 100 nM). With succinate as substrate, Mn2+ inhibited oxygen consumption by suspensions of rat liver mitochondria after the addition of ADP but not after the addition of uncoupler. With glutamate/malate as substrate, Mn2+ inhibited ADP-stimulated respiration and also slightly inhibited uncoupler stimulated respiration. State 4 (resting) respiration was unchanged in all cases, indicating that the inner membrane retained its impermeability to protons. These results suggest that Mn2+ was not oxidized and that it can interfere directly with oxidative phosphorylation, most likely by binding to the F1 ATPase. Mn2+ may also bind to the NADH dehydrogenase complex, but not strongly enough to affect electron transport in vivo. It is suggested that accumulation of manganese within the mitochondria of globus pallidus may help explain the distinctive pathology of manganism. PMID- 1631889 TI - The genetic toxicology of cobalt. AB - Genetic and related effects of cobalt compounds are reviewed and discussed with respect to mechanisms. In prokaryotic assays, Co(II) salts generally are nonmutagenic. In Saccharomyces cerevisiae, CoCl2 is mutagenic to mitochondrial genes and weakly mutagenic or nonmutagenic to chromosomal genes. In plants, Co(II) salts induced gene mutations and chromosomal aberrations. In mammalian cells in vitro, Co(II) compounds caused DNA strand breaks, sister-chromatid exchanges and aneuploidy, but not chromosomal aberrations. In two cell lines, CoCl2 was weakly mutagenic. Interestingly, the poorly soluble compound CoS caused DNA strand breaks and morphological transformation of mammalian cell lines. In contrast to its weak clastogenic and mutagenic properties, cobalt(II) exerts pronounced antimutagenicity in bacteria and mostly comutagenic effects in mammalian cells. In Escherichia coli CoCl2 lowered the frequency of mutations induced by MNNG, uv or X rays. In Chinese hamster V79 cells, CoCl2 enhanced the mutagenicity and clastogenicity of uv light but not of gamma rays. Regarding direct genotoxic mechanisms, Co(II) induces the formation of reactive oxygen species when combined with hydrogen peroxide in cell-free systems. At high (i.e., millimolar) concentrations, Co(II) also decreases the fidelity of DNA synthesis. Regarding anti- and co-mutagenic mechanisms, evidence for the interference of Co(II) with DNA repair processes is discussed. These mechanisms are regarded as relevant for the risk assessment of human exposure to cobalt in combination with other agents. PMID- 1631888 TI - Differential expression and induction of UDP-glucuronosyltransferase isoforms in hepatic and extrahepatic tissues of a fish, Pleuronectes platessa: immunochemical and functional characterization. AB - Glucuronidation of three substrates prototypical for different UDP glucuronosyltransferase (UDPGT) isoforms in hepatic, renal, intestinal, and branchial microsomes of corn oil, 3-methylcholanthrene, Aroclor 1254, and clofibrate-pretreated plaice was investigated. The differential expression of UDPGT in the four tissues clearly demonstrated for the first time that multiple isoforms with differing substrate specificities were present in fish. The liver was quantitatively the most important site for the glucuronidation of all three compounds studied. Phenol UDPGT activity was ubiquitous to all tissues and was induced by 3-methylcholanthrene and Aroclor 1254 in hepatic tissue and by Aroclor 1254 in renal tissue. The glucuronidation of testosterone was restricted to liver and intestinal tissue, while conjugation of bilirubin was expressed solely in hepatic tissue. The biotransformation of the endogenous compounds was not induced in the xenobiotic-treated animals. The presence of immunoreactive UDPGTs in the four tissues was demonstrated by immunoblot analysis using sheep anti-plaice UDPGT antibodies. Hepatic tissue displayed a range of immunoreactive polypeptides of 52 to 57 kDa, while a 55-kDa polypeptide was detected in extrahepatic tissues. An increased intensity of the latter polypeptide species was demonstrated in liver and kidney microsomes in which there was a concomitant induction of phenol UDPGT activity in xenobiotic-treated fish. The results indicate that the 55-kDa polypeptide was the major polyaromatic hydrocarbon-inducible UDPGT isoenzyme in hepatic and renal microsomes. PMID- 1631890 TI - Acrylamide disrupts elemental composition and water content of rat tibial nerve. I. Myelinated axons. AB - The mechanism by which acrylamide (ACR) produces distal axonopathy in humans and laboratory animals is unknown. The possibility that this neuropathy involves deregulation of elements and water in rat peripheral nerve has been investigated. Electron probe X-ray microanalysis was used to measure percentages of water and concentrations (mmol element/kg dry or wet wt) of Na, P, S, Cl, K, Ca, and Mg in axoplasm and mitochondrial areas of tibial nerve axons. Results show that when rats were intoxicated with ACR by either the oral (2.8 mM in drinking water, up to 60 days) or the intraperitoneal (ip, 50 mg/kg/day x 5 or 10 days) route, a progressive loss of internodal axoplasmic K, Cl, and Na regulation was observed in subpopulations of myelinated fibers. Elemental deregulation was manifest as a shift in mean elemental content, widening of the corresponding concentration range, and a statistically significant increase in data variance. In internodal axonal regions, elemental composition of mitochondrial areas was not altered by ip ACR intoxication, whereas oral exposure was associated with delayed changes in Na, K, Cl, Ca, and Mg. In swollen axons, axoplasm and mitochondrial areas exhibited complete loss of element and water compartmentalization. This global decompartmentalization of swollen axons was quantitatively similar regardless of the route or length of ACR exposure. The results of this study suggest that a progressive loss of elemental regulation in axoplasm of myelinated tibial nerve fibers might be mechanistically related to ACR neurotoxicity. PMID- 1631891 TI - Acrylamide disrupts elemental composition and water content of rat tibial nerve. II. Schwann cells and myelin. AB - The effects of subchronic and subacute acrylamide (ACR) intoxication on elemental composition (Na, P, S, Cl, K, Ca, Mg) and water content of Schwann cell body cytoplasm and myelin were assessed in rat tibial nerve. Electron probe X-ray microanalysis demonstrated that, in control rats, peripheral nerve glia and myelin exhibited highly characteristic distributions of elements and water and that ACR intoxication was associated with disruption of this normal subcellular distribution. When rats were intoxicated with ACR by either the oral (2.8 mM in drinking water for 15, 22, 30, and 60 days) or the intraperitoneal (50 mg/kg/day x5 and 10 days) route, an exposure-dependent loss of cytoplasmic Na, K, P, Cl, Mg, and water regulation was detected in Schwann cell cytoplasm. Maximum development of elemental deregulation occurred after 30 days of oral ACR exposure and 10 days of ip treatment. The cytoplasmic elements involved and their corresponding quantitative changes were similar regardless of the route of ACR intoxication. Analysis of myelin revealed that both oral and parenteral ACR exposure caused early, persistent increases in dry weight Na, P, and water content. However, Cl dry weight concentrations were increased by oral exposure and decreased by ip ACR injection. Results of this study indicate that ACR intoxication is associated with a significant disturbance of subcellular element and water distribution in tibial nerve Schwann cells and myelin. The pattern of elemental disruption is typical of reversible cell damage and, therefore, Schwann cell injury might play a role in the expression of ACR neurotoxicity. PMID- 1631892 TI - Protection of rhesus monkeys against soman and prevention of performance decrement by pretreatment with acetylcholinesterase. AB - The ability of acetylcholinesterase from fetal bovine serum (FBS AChE) to protect against soman, a highly toxic organophosphorus (OP) compound, was tested in rhesus monkeys. Intravenous administration of FBS AChE produced a minimal behavioral effect on the serial probe recognition task, a sensitive test of cognitive function and short-term memory. Pharmacokinetic studies of injected FBS AChE indicated a plasma half-life of 40 hr for FBS AChE in monkeys. Both in vitro and in vivo titration of FBS AChE with soman produced a 1:1 stoichiometry between organophosphate-inhibited FBS AChE and the cumulative dose of the toxic stereoisomers of soman. Administration of FBS AChE protected monkeys against the lethal effects of up to 2.7 LD50 of soman and prevented any signs of organophosphate intoxication, e.g., excessive secretions, respiratory depression, muscle fasciculations, or convulsions. In addition, monkeys pretreated with FBS AChE were devoid of any behavioral incapacitation after soman challenge, as measured by the serial probe recognition task. Compared to the current multicomponent drug treatment against soman, which does not prevent the signs or the behavioral deficits resulting from OP intoxication, use of FBS AChE as a single pretreatment drug provides significantly effective protection against both the lethal and the behavioral effects of soman. PMID- 1631893 TI - Therapeutic efficacy of HI-6 in soman-poisoned marmoset monkeys. AB - The therapeutic efficacy of the oxime HI-6 against intoxication with the irreversible cholinesterase (ChE) inhibitor soman was tested in marmoset monkeys. Five out of six marmosets, intoxicated with 5 x LD50 soman and treated immediately with diazepam (0.2 mg.kg-1 iv) and 15 sec later with atropine (0.5 mg.kg-1 im) and HI-6 (50 mg.kg-1 im), survived for more than 24 hr. One of these animals died after 4 days. In the HI-6-treated marmosets blood ChE activity was inhibited at a rate slower than that in three animals treated similarly but with saline instead of HI-6. The latter marmosets died within 8 min after soman. HI-6 achieved its plasma peak 5 min after injection and was eliminated with a t1/2 of about 40 min. In a second experiment similarly treated marmosets were euthanized at 5 min (three saline-treated animals) or at 10 min (three HI-6-treated animals) after the soman intoxication to enable the determination of acetylcholinesterase (AChE) activities in diaphragm and brain tissue. In addition, in these animals blood AChE and butyrylcholine esterase (BuChE) activities were determined. Low AChE activities were encountered in diaphragms and brains. These levels were not significantly different between saline- and HI-6-treated marmosets. In vitro treatment with HI-6 at 40 min after soman still led to an increase of the AChE activity, which was significant in diaphragm, suggesting that postmortem AChE inhibition had occurred. The ratio of AChE to BuChE in blood was significantly enhanced in HI-6-treated animals, indicating that HI-6 preferentially reactivated AChE. It is concluded that (i) HI-6 is an effective treatment against soman poisoning in marmosets and (ii) AChE reactivation or protection by HI-6 contributed to the survival of the animals. PMID- 1631895 TI - Exposure to methyl mercury from birth to adulthood impairs high-frequency hearing in monkeys. AB - Hearing deficits are a frequent consequence of both developmental and adult methyl mercury exposure in humans. However, a detailed characterization of these deficits has not been performed in either humans or animals. Cynomolgus monkeys (Macaca fascicularis) were dosed from birth to 7 years of age with 50 micrograms/kg/day of mercury as methyl mercuric chloride. Steady-state blood mercury levels during dosing were 0.6-0.9 ppm. When monkeys were 14 years old, pure tone detection thresholds were determined by a psychophysical procedure. Control monkeys exhibited thresholds at frequencies between 125 and 31,500 Hz comparable to previously published values for macaques. One methyl mercury treated monkey exhibited normal detection thresholds at all frequencies. Three treated monkeys were impaired at the second highest frequency tested (25,000 Hz) and therefore were not tested at 31,500 Hz. The fifth treated monkey displayed severely elevated thresholds at middle frequencies (10,000-12,500 Hz), precluding testing at higher frequencies. These results indicate a selective high-frequency deficit in monkeys exposed to methyl mercury from birth to adulthood and not exposed to methyl mercury in the 7 intervening years before auditory testing. These findings extend previous results in this group of monkeys in which deficits in spatial and temporal visual function were observed. PMID- 1631894 TI - Involvement of nonparenchymal cells in oxygen-dependent hepatic injury by allyl alcohol. AB - Allyl alcohol injury to hepatocytes in the perfused liver is oxygen-dependent. It is not known if this injury involves direct action of allyl alcohol on hepatocytes or requires participation of other cell types (e.g., Kupffer cells) present in the liver. Accordingly, the action of allyl alcohol (100-500 microM) on isolated hepatocytes was studied using cells maintained at either 95 or 21% O2. Allyl alcohol toxicity, as indexed by trypan blue uptake, lactate dehydrogenase release, and ATP content, did not differ in the two groups of cells, suggesting that O2 dependency of allyl alcohol toxicity involves other cell types. Administration of allyl alcohol (30 or 40 mg/kg, ip) to rats caused extensive hepatic necrosis localized primarily to periportal regions. To test the involvement of Kupffer cells in the genesis of this injury, male rats (200-350 g) were treated with gadolinium chloride (GdCl3, 10 mg/kg, iv) which diminishes Kupffer cell function and number. The extent of hepatic damage assessed by light microscopy and serum enzymes, aspartate aminotransferase and alanine aminotransferase, was markedly attenuated by pretreatment of rats with GdCl3 24 hr prior to allyl alcohol injection. Thus, O2-dependent hepatic necrosis caused by allyl alcohol involves the presence of Kupffer cells. Since GdCl3 did not prevent toxicity in the perfused liver, circulating blood elements may also contribute to injury of the liver by allyl alcohol in vivo. PMID- 1631896 TI - Role of hepatic lysosomes in the degradation of metallothionein. AB - The degradation of metallothionein (MT) by rat liver was examined. Degradation of MT by liver homogenate was greater than by cytosol. In addition, MT degradation by the homogenate at pH 5.5 was more than that at pH 7.2. Because lysosomal proteases function at acidic pH, these findings suggest the importance of lysosomes in MT degradation. The degradation by the lysosomal fraction was about 400-fold greater than that by the cytosol. Because cathepsins are the principal lysosomal proteases, we used cathepsin-specific inhibitors, such as leupeptin, E 64 and pepstatin, to determine the relative importance of different cathepsins in degrading MT. The study reveals that cathepsin B and/or L is (are) probably the most important enzyme(s) in degrading hepatic MT, because leupeptin, which blocks cathepsin B and L activity, inhibited the degradation of apo-MT by about 80%. Cathepsin D appears to be of least importance in MT degradation, because inhibition of this enzyme by pepstatin reduced degradation by only 20%. Studies on the degradation of apo-MT, ZnMT, and CdMT indicated that apo-MT is about 1500 fold more sensitive to degradation than ZnMT and CdMT. These data suggest that metals protect MT from degradation. This is further supported by a reconstitution experiment, which shows that with a progressive decrease of MT: metal ratio following titration of apo-MT by metals, there is a concomitant reduction in degradation. At a lysosomal pH of around 4.7, about 60% of Zn and 20% of Cd are displaced from MT, thereby making it susceptible to degradation. We propose, therefore, that lysosomes are probably important for MT degradation in vivo and that metal release is a prerequisite for degradation. With the release of metals, MT becomes susceptible to degradation, which is probably accomplished by the lysosomal cathepsins, in particular cathepsins B and L. PMID- 1631897 TI - Generation of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene by murine splenic macrophages. AB - Studies have demonstrated that macrophages are the cell types which metabolize benzo[a]pyrene (B[a]P) within the murine spleen. B and T cells, polymorphonuclear cells, or the splenic capsule did not produce amounts of B[a]P metabolites above those of background. Exposure of mice to B[a]P, a known inducer of isozymes of cytochrome P450, resulted in an increase in the amounts of some B[a]P metabolites generated by macrophages. Evaluation of the in vitro plaque-forming-cell response to several T-cell and macrophage-dependent antigens following in vivo exposure to B[a]P indicated that the macrophage is the cell type responsible for B[a]P induced immunosuppression. While suggestive, the reported data have not definitively established that an enriched splenic macrophage population can generate 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-B[a]P (BPDE) from B[a]P 7,8,-dihydroxy-7,8-dihydrodiol (B[a]P-7,8-diol). These data are critical to our hypothesis that the splenic cell type(s) which form BPDE will be the primary target cell responsible for B[a]P-induced immunosuppression. The first objective was to determine if splenic macrophages could generate BPDE. Enriched (80-90% purity) populations of macrophages were incubated with [3H]B[a]P for 24 hr. BPDE generated was quantitated by analysis of the cis- and trans-tetrol hydrolysis products of BPDE via HPLC procedures. Splenic macrophages generated BPDE from B[a]P. The cis syn was the predominate tetrol detected. Exposure of mice to B[a]P increased the amounts of the trans-anti-tetrols 2.2-fold, the trans-syn-tetrols 2.0-fold, the cis-anti-tetrols 1.8-fold, and the cis-syn-tetrols 2.6-fold above those formed by macrophages of vehicle-exposed mice. Both cytochrome P450- and peroxyl radical-dependent pathways are known to oxidize B[a]P-7,8-diol to BPDE. Since macrophages were found to generate BPDE, the second objective was to investigate which enzymatic pathway was responsible for its formation. The B[a]P (+)-7,8-diol isomer has been shown to produce different specific BPDE isomers via the cytochrome P450 and peroxyl radical pathways. Macrophage populations were incubated with [3H]B[a]P-(+)-7,8-diol for 24 hr and the contribution of the cytochrome P450 and peroxyl radical pathways to BPDE formation determined by detection of syn-BPDE-hydrolysis and anti-BPDE-hydrolysis products, respectively. Based on the ratio of anti/syn BPDE-derived tetrol products, the results demonstrate that splenic macrophages can generate the BPDE by both a cytochrome P450-dependent and -independent (peroxyl radical) pathway. Macrophages are the cells which metabolize B[a]P within the murine spleen and may be the cell type responsible for B[a]P-induced suppression of humoral immune responses. PMID- 1631898 TI - Alterations in the cortical thymic epithelium of rats after in vivo exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): an (immuno)histological study. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces thymic atrophy in rats. The present study was initiated to provide (immuno)histological data on the mechanism of action. Juvenile male Wistar rats were orally intubated once with 50 or 150 micrograms/kg TCDD. They were euthanized 4 or 10 days thereafter, or were allowed to stay alive until Day 20 or 26. Growth retardation occurred rapidly in all TCDD treated animals. Lethality was demonstrated within 20-21 days after administration. At Days 4 and 10 after intubation, thymic atrophy was shown by reduction of thymic weight and cortex/medulla ratio. Staining patterns for T-cell markers in the atrophic thymuses coincided with the reduction of cortical areas. There was no evidence indicating that the effects were indirectly caused by stress. TCDD-induced thymic atrophy persisted until Day 26 after administration. Immunohistochemical analysis revealed prominent changes in the cortical thymic epithelium at the 150-micrograms/kg dose level. First, in the cortex epithelial cell aggregates were observed both at Day 4 and at Day 10 after administration. Apparently, the architecture of the epithelium had changed in these animals. Second, at 10 days after administration epithelial cells were found with the simultaneous expression of markers that in the normal uninvoluted thymus only occur either in the subcapsular/medullary area or in the cortex. This phenotype points to an unusual stage of differentiation. We conclude that TCDD exposure affects the cortical epithelium of the rat thymus at a high dose level. Apparently, it disturbs the epithelial network and interfers with the differentiation of epithelial cells. PMID- 1631899 TI - Cutaneous toxicity and absorption of paraquat in porcine skin. AB - Paraquat, a commonly used herbicide, has been shown to be toxic in exposed field workers. The objectives of this study were to (a) assess the cutaneous toxicity of paraquat in vivo in pig skin and in vitro in the isolated perfused porcine skin flap (IPPSF) and (b) quantitate its absorption in the IPPSF. The amounts of 3, 24, and 200 mg of paraquat were topically applied (5 cm2 surface area) on the ventral abdomen of pigs and biopsied after 6-8 hr for light microscopy (LM) and transmission electron microscopy (TEM). IPPSFs were topically dosed with the same concentrations and perfused for 8 hr (n = 4/treatment). The dosed area of the skin was sampled for LM, TEM, and enzyme histochemistry. IPPSFs were also treated topically with [14C]paraquat dichloride at the aforementioned concentrations (n = 4/dose) and hourly perfusate samples were collected for radiolabel determination and assessment of biochemical and physiological parameters. The epidermal changes were similar both in vivo and in vitro. The changes included epidermal intercellular edema which increased with dose and epidermal-dermal separation at the 200-mg dose. Acid phosphatase and nonspecific esterase activities were increased in the upper layers of the epidermis, while alkaline phosphatase showed a greater activity in the stratum basale layer. Glucose utilization of all treated IPPSFs was lower than that of the controls and a variation in the vascular resistance profiles was seen in all the treated flaps. Radiotracer studies indicated that a majority of the compound remained on top of the application site and minimal absorption or penetration into skin was observed. Thus, at high concentrations and prolonged exposure, paraquat may have deleterious effects on epidermal morphology in the absence of significant percutaneous absorption. PMID- 1631900 TI - p-aminophenol nephrotoxicity: biosynthesis of toxic glutathione conjugates. AB - p-Aminophenol causes necrosis of the pars recta of the proximal tubules in rats, and its nephrotoxicity may be due to glutathione-dependent bioactivation reactions. We have investigated the hepatic metabolism of p-aminophenol in Wistar rats and the cytotoxicity of formed glutathione S-conjugates in rat renal epithelial cells. After ip application of p-aminophenol (100 mg/kg), the following metabolites were identified in rat bile: 4-amino-2-(glutathion-S yl)phenol, 4-amino-3-(glutathion-S-yl)-phenol, 4-amino-2,5-bis(glutathion-S yl)phenol, 4-amino-2,3,5(or 6)-tris(glutathion-S-yl)phenol, an aminophenol conjugate (likely a sulfate or glucuronide), acetaminophen glucuronide, and 3 (glutathion-S-yl)acetaminophen. 4-Amino-3-(glutathion-S-yl)phenol, 4-amino-2,5 bis(glutathion-S-yl)phenol, and 4-amino-2,3,5(or 6)-tris(glutathion-S-yl)phenol induced a dose- and time-dependent loss of cell viability in rat kidney cortical cells. Cell killing was significantly reduced by inhibition of gamma-glutamyl transpeptidase with Acivicin. p-Aminophenol was also toxic to renal epithelial cells. Coincubation of p-aminophenol with tetraethylammonium bromide, a competitive inhibitor of the organic cation transporter, and with SKF-525A, an inhibitor of cytochrome P450, protected cells from p-aminophenol-induced toxicity. p-Aminophenol would thus be accumulated in the kidney mainly by organic cation transport systems, which are concentrated in the S-1 segment of the proximal tubule. However, p-aminophenol toxicity in vivo is directed toward the S 2 and S-3 segments, which are rich in gamma-glutamyl transpeptidase. These results and the observation that biliary cannulation and glutathione depletion reduce p-aminophenol nephrotoxicity suggest that the biosynthesis of toxic glutathione conjugates is responsible for p-aminophenol nephrotoxicity in vivo. The aminophenol glutathione S-conjugates formed induce p-aminophenol nephrotoxicity by a pathway dependent on gamma-glutamyl transpeptidase. PMID- 1631901 TI - The hepatotoxicity of chloroform in precision-cut rat liver slices. AB - Chloroform hepatotoxicity was investigated in precision-cut liver slices from male Sprague-Dawley rats pretreated with phenobarbital to predispose animals to CHCl3 intoxication. Liver slices were exposed to 0.2, 0.5 and 1.0 mM chloroform for a total of 9 h in a roller culture system. Intracellular K+ loss was found to be concentration- and time-dependent over the duration of the experiment. Histopathological changes were also evident. Glucose 6-phosphate dehydrogenase and beta-glucuronidase were significantly decreased at 3 h relative to controls where a loss of 61% and 36% occurred, respectively. Enzyme levels of alanine aminotransferase and lactate dehydrogenase, both found predominantly in periportal hepatocytes, remained identical to controls over the duration of the experiment. A significant time-dependent depletion of glutathione occurred as early as 3 h following the administration of 0.5 mM chloroform. Mitochondrial viability, measured by the reduction of a specific dye, was significantly lower than controls in treated slices at 6 h following chloroform administration. Precision-cut liver slices appear to be especially useful for the biochemical and histopathological examination of site-specific hepatotoxicants such as CHCl3. PMID- 1631902 TI - Methylamine metabolism to formaldehyde by vascular semicarbazide-sensitive amine oxidase. AB - The capacity of the vascular enzyme, semicarbazide-sensitive amine oxidase (SSAO), to metabolize methylamine to the potentially toxic product, formaldehyde, was tested using rat aortic homogenates and purified porcine aortic SSAO. Formaldehyde production in incubations of enzyme source with methylamine (1 mM) was detected by high performance liquid chromatography and product was confirmed by desorption chemical ionization mass spectrometry (DCI-MS). Inhibitor studies using the specific SSAO inhibitor semicarbazide and the monoamine oxidase inhibitor pargyline indicate that SSAO is responsible for metabolism of methylamine to formaldehyde. These results suggest the possibility that elevated methylamine found in several pathologic states (such as uremia and diabetes mellitus), or generated from exogenous sources, could result in overproduction of formaldehyde in tissues with high SSAO activity, especially blood vessels. PMID- 1631903 TI - Toxicity assessment of toxins T-514 and T-544 of buckthorn (Karwinskia humboldtiana) in primary skin and liver cell cultures. AB - The present study was undertaken to assess and compare the in vitro cytotoxicity of toxins T-514 and T-544 of Buckthorn (Karvinskia humboldtiana) using primary cultures of rat hepatocytes and keratinocytes. Cell cultures were exposed to 6, 12, 25 and 50 microM concentrations of the toxins for 2, 4, 6 and 24-h periods. Cytotoxicity was determined by release of the cytoplasmic enzyme, lactate dehydrogenase (LDH), in culture media, methylthiazoltetrazolium (MTT) reduction and neutral red (NR) uptake. An increase in LDH leakage was observed in liver cell cultures as early as 2 h with 50 microM T-544 and with 6 microM T-514 and T 544 at 6 h and 24 h, respectively. In the NR assay the toxicity was evident at 2 h with 12 microM T-514 and T-544 and with 6 microM concentrations of both toxins at 6 h. On the other hand, a decrease in MTT reduction was detected at 4 h with 50 microM concentrations of both toxins and with 25 microM T-544 and 12 microM T 514 at 6 h and 6 microM T-514 and T-544 at 24 h. Both toxins were shown to be highly hepatotoxic; T-514 was more toxic than T-544. In the skin cell cultures, the toxicity of the toxins was not as severe and was not expressed until 12 h of exposure. PMID- 1631904 TI - Actin filament alteration as a potential marker for cholestasis: a study in isolated rat hepatocyte couplets. AB - It has been suggested that modification of the pericanalicular microfilament network (F-actin) plays a role in cholestasis. The purposes of this study were to assess (i) the process of F-actin network reorganization in isolated rat hepatocyte couplets (IRHC) in order to define the optimal study conditions in this model, (ii) the effect of cholestatic and hepatotoxic but non-cholestatic compounds on F-actin distribution in IRHC. F-actin was stained with fluorescein isothiocyanate phalloidin and fluorimetric measurements were performed in single couplets using a scanning laser cytometer, ACAS 570. F-actin distribution was assessed by the ratio of canalicular area fluorescence/total couplet fluorescence (CF/TF). The organization of the F-actin filaments was restored in IRHC 3-6 h after plating. At non-cytotoxic concentrations, most cholestatic compounds induced a significant accumulation of F-actin around the bile canaliculus as indicated by increased fluorescence in the pericanalicular area and by the increased CF/TF ratio as compared to the controls. This accumulation could be a consequence of an inhibition of F-actin depolymerization or a higher organization of actin (redistribution, bundling or reorientation). Hepatotoxic but non cholestatic compounds did not induce any change in pericanalicular F-actin. Abnormalities of pericanalicular F-actin therefore appear to be a specific marker of hepatocellular cholestasis. PMID- 1631905 TI - Formation and identification of protein adducts to cytosolic proteins in guinea pig liver slices exposed to halothane. AB - The anesthetic halothane can be bioactivated to the reactive intermediate, trifluoroacetyl chloride, which can covalently bind to liver protein. The product of this reaction is trifluoroacetyl-N-epsilon-lysine which can act as a foreign epitope in altering both protein immunogenicity and antigenicity. An in vitro liver slice system was used to study the formation of protein adducts following exposure to halothane. Liver slices (30-35 mg wet weight, 250-300 microns thick) from adult male Hartley guinea pigs (600-800 g) were exposed to [14C]halothane (0.6-0.9 microCi, 1.0-1.7 mM) in 95% O2/5% CO2 for 1, 6 and 12 h. The slices were homogenized and subcellular fractions prepared. Proteins were resolved by electrophoresis and bound radioactivity was detected by scintillation counting and autoradiography. Greater than 80% of detectable radioactivity to whole liver cell protein was localized in the 20-30-kDa range and increased in a linear fashion over the 12-h incubation period. Covalent binding was localized to two proteins of 27 kDa and 26 kDa present in the cytosolic compartment. Purification followed by N-terminal amino acid sequence analysis of the 27-kDa protein has identified it to be homologous with glutathione-S-transferase b. This cytosolic protein appears to be the major target for trifluoroacetylation in liver slices exposed to halothane. PMID- 1631906 TI - Inhibition of protein synthesis in liver and kidney of mice by bolesatine: mechanistic approaches to the mode of action at the molecular level. AB - Protein synthesis was assayed in liver and kidney of mice treated with bolesatine, a toxic glycoprotein from the mushroom Boletus satanas (Lenz) which was previously shown to be an inhibitor of protein synthesis by cell-free systems in vitro and by cultured cell-lines. Protein synthesis in vivo (Swiss mice) is inhibited in a dose-dependent manner in liver and kidney. The mechanism of action does not appear to be due to RNA-N-glycosidase activity of bolesatine or a RNAase activity of this toxin on the ribosomal RNAs. Ribosomes do not appear to be damaged by pretreatment with bolesatine as judged by a poly(U) translation system. Thus bolesatine cannot be included in the group of protein synthesis inhibitors of plant origin known as ribosome-inactivating proteins (RIPs). PMID- 1631907 TI - Host resistance to Trichinella spiralis infection in rats and mice: species dependent effects of cyclophosphamide exposure. AB - Host resistance to Trichinella spiralis infection was compared in male rats (F344) and female mice (C57BL/6J) following various cyclophosphamide (CY) treatment schedules. Doses of CY given to mice were adjusted by body surface area to be comparable to rat doses. Adult parasite elimination was not affected by oral administration of 1.5, 3 or 6 mg CY/kg per day to rats or 1.05, 2.1 or 4.2 mg CY/kg per day to mice for 10 days. In rats, resistance was suppressed by a single oral dose of 80 mg/kg given the day prior to infection, but was not affected at 20 or 40 mg/kg. A single oral dose of 14, 28 or 56 mg CY/kg did not affect parasite expulsion in mice. Rats were also given four daily intraperitoneal (i.p.) injections of 20, 40 or 80 mg CY/kg per day and mice received 14, 28 or 56 mg CY/kg per day. Infected rats did not survive at the two higher dose levels and parasite expulsion was suppressed at 20 mg/kg per day; parasite expulsion was suppressed in mice by four i.p. injections of 56 mg CY/kg per day, but not by lower doses. In rats, doses of CY which suppressed adult parasite expulsion also severely suppressed the proliferative response of mesenteric lymph node cells (MLNC) to an extract of T. spiralis (TsE). However, significant suppression of TsE-driven blastogenesis occurred at a dose of CY which did not affect parasite expulsion, indicating that the proliferative response in rats was more sensitive to suppression than actual parasite elimination. In contrast, the proliferative response to the T cell mitogen concanavalin A was elevated in the MLNC of CY-exposed rats. This was determined to be related to the interval between CY dosing and the day of assay rather than to an effect of infection with T. spiralis. Mouse MLNC proliferative responses to TsE were not suppressed by CY treatment, even at levels of CY which suppressed adult parasite expulsion. Mice differed from rats in that CY exposure did not affect the proliferative response to concanavalin A in infected animals. The species-dependent differences observed in these studies may have been secondary to the greater sensitivity of rats to CY. Nonetheless, these results highlight the potential for species-specific responses to chemical exposure and underscore the need for additional comparative studies of host resistance in rats and mice. PMID- 1631908 TI - [Anatomy and revolution of the human image]. AB - In Bourgery's and Jacob's "Traite complet de l'anatomie de l'homme", Paris 1831 1854, the revolution Davidienne had been introduced into the plates of anatomical atlasses. Unlike the Vesalian tradition of representation this demarcation against an old world provided a new picture of man in medical illustration. The cultural development taking us to this point is discussed against the background of converging movements in art and medicine in late 18th century France evolving sovereign man as a modern individual. PMID- 1631909 TI - [Karl Sudhoff and medical history sources. A contribution to his collections and exhibits]. PMID- 1631910 TI - [The medical journal of Hans Kehr (1862-1916) from 1905 to 1910 as a medical history document]. PMID- 1631911 TI - Asaph's 'book of remedies': Greek science and Jewish apologetics. PMID- 1631912 TI - [Anorexia nervosa in German medical literature 1900 to 1945. The role of anorexia nervosa in the origin of psychosomatic medicine]. AB - German-language publications on anorexia nervosa and Simmonds' disease from between 1900 and 1945 are reviewed in order to trace factors inherent in medical thinking which have mostly hindered German-language medicine in understanding anorexia nervosa. It is demonstrated that a) the few German-language physicians who did describe central and possible characteristics of a.n. (weight-phobia, overactivity, bulimia, self-induced vomiting) were enabled to do so by valuing detailed clinical description, also of psychic characteristics, and an interest in the neuroses; b) the concept of anorexia nervosa was better known than previously assumed, though largely misunderstood; c) typical diagnostic misinterpretations led to typical biases in the description of the syndrome; d) in Germany more than in other countries a.n. was confounded with Simmonds' disease; and e) in addition to other factors, one reason for this lay in the 'holistic' ideal of psychosomatic medicine in the 1930s. PMID- 1631913 TI - [Petrarca and the plague]. AB - The author presents a synopsis of Petrarch's reflections and experiences during the plague of 1348 and the following alterations in Italian society. The great humanist and celebrated poet was an excellent observer of the reactions of his contemporaries and the various cultural and moral consequences of the "Black Death" catastrophe. He feels deep desperation but emphasizes stoic acceptance of fate and Christian humility. His letters concerning plague and death are impressive documents of the "interior life" of European intellectuals in midfourteenth century. They reveal the helplessness of scholastic medical doctors and the crisis of contemporary medicine. PMID- 1631914 TI - Treating the Grail King: astrology and medicine in book XVI of Wolfram's "Parzival". PMID- 1631915 TI - ['Physica' of Hildegard von Bingen as a source for the 'Kochbuch Meister Eberhards']. AB - In this article a previously unknown fragment of Saint Hildegards 'Physica' is added to the list of extant manuscripts. Extracts from three books of the 'Physica' ("De Plantis", "De Piscibus", and "De Avibus") were found to be incorporated in a late-medieval German cookbook, the 'Kochbuch Meister Eberhards'. While the German sources for the cookbook, such as the 'Regel der Gesundheit' and the 'Breslauer Arzneibuch' have been known for some time, the Latin parts have traditionally been neglected by scholars. Neither were they included in the 1963-edition of the cookbook nor studied in any detail in the past. The discovery of the 'Physica' as their source provides us with new insights into Eberhard's compiler-work and the literature which was available to him, as well as the reception of Hildegard's medical writings in the fifteenth century. PMID- 1631916 TI - [Sudhoff's viewpoint of ancient medicine]. AB - Sudhoff's views of the tasks of medical historians in the field of the history of ancient medicine were influenced by the contemporary controversy between classical philologists and medical historians about their competence. On the one hand Sudhoff thought the philologic historical method to be the appropriate one for the investigation of the history of ancient medicine, on the other hand he did not think it to be indispensable for the medical historians. Their main task was in his eyes to publish new items from archaeological and literary sources, as he himself did. PMID- 1631917 TI - The case for local immunosuppression. PMID- 1631918 TI - A decrease in graft-vs.-host disease without loss of graft-vs.-leukemia reactivity after MHC-matched bone marrow transplantation by selective depletion of donor NK cells in vivo. AB - It is thought that natural killer cells may play a role in graft-vs.-host reactions after allogeneic bone marrow transplantation, but the use of NK cell specific reagents has been limited. In this report, an NK allele-specific monoclonal antibody, anti-NK 1.1, was used to study the impact of in vivo donor NK cell depletion on GVH disease, graft-vs.-leukemia (GVL) reactivity and donor T cell chimerism after allogeneic murine BMT. AKR/J (H-2k) recipient mice were preconditioned with suboptimal irradiation (9 Gy = LD50) and transplanted with major histocompatibility complex-matched B10.BR (H-2k) BM cells with or without added spleen cells as a source of T cells. The addition of increasing numbers of spleen cells to the BM inoculum produced GVHD of varying intensities. The beneficial effect of NK depletion on GVHD was dependent on the intensity of the GVH reaction. Donor NK cell depletion had no effect on the survival of mice with severe GVHD after MHC-matched BMT (B10.BR into AKR) or after MHC-mismatched BMT (B10.BR into DBA/2; H-2k into H-2d). However, donor NK depletion increased survival of AKR hosts given sufficient B10.BR splenic T cells to induce mild-to moderate GVHD. Ex vivo depletion of donor CD8+ T cells also reduced GVH associated mortality, but the use of both CD8 and NK depletion offered no improvement over either alone, suggesting an interaction between CD8+ and NK 1.1+ cells. In contrast to CD8 depletion, donor NK depletion did not compromise the rapid and complete establishment of donor T cell chimerism nor the ability of chimeras to mount an effective GVL reaction. Thus, elimination of donor NK cells provides an alternate strategy for reducing GVHD without loss of GVL reactivity following MHC-matched allogeneic BMT. PMID- 1631919 TI - Suppression of anti-skin-allograft response by photodamaged effector cells--the modulating effects of prednisolone and cyclophosphamide. AB - Using a murine model of skin allotransplantation, we have demonstrated previously that inhibition of specific response to alloantigen is inducible by immunization of the host with intravenously administered photoinactivated antigraft effector T cells. This hyporesponsiveness, which was demonstrated by specific inhibition of mixed leukocyte culture (MLC), inhibition of cytotoxic T lympholysis (CTL), specific suppression of the delayed type hypersensitivity (DTH) response, and prolongation of specific skin allograft survival, was adoptively transferable by CD8+ radiosensitive T lymphocytes. In this study, we extend those results to evaluate the effects of an immunosuppressive agent (prednisolone) and an alkylating drug (cyclophosphamide) on the induction of this specific suppressive cellular response. Our results reveal that the administration of prednisolone reduces the induction of the specific hyporesponsiveness to alloantigen, as demonstrated by maintenance of the DTH response to alloantigen and continued accelerated rejection of skin allografts. In contrast, the administration of cyclophosphamide augmented this specific suppressive response to alloantigen in the DTH assay and in prolongation of specific skin allograft survival. These results indicate that adjuvant immunomodulating chemotherapy alters the immune response to photoinactivated effector T cells. PMID- 1631920 TI - A canine model for hepatic venoocclusive disease. AB - Hepatic venoocclusive disease is a frequent lethal complication of bone marrow transplantation. It has also been associated with hepatic irradiation and administration of chemotherapeutic agents without BMT. The pathogenesis and therapy of VOD are unclear. The present studies were directed at developing a canine model for VOD. Three groups of dogs were studied. Group one consisted of 8 dogs in which monocrotaline (MC) was administered at 125 mg/kg orally on an intermittent schedule. In 7 of the 8 dogs 6 to 9 doses of drug were administered between 42 and 110 days. Group 2 consisted of 6 dogs receiving busulfan 2 mg/kg/day for 17-25 days, when platelet counts decreased to less than 5 x 10(4)/mm3 or clinical bleeding occurred. Group 3 consisted of 2 dogs receiving 24 Gy and 4 dogs receiving 36 Gy of whole-liver irradiation. Seven of 8 dogs in group 1 developed significant liver function abnormalities and evidence of portal hypertension. Histologic findings of VOD were present at autopsy. Group 2 dogs failed to develop clinical or laboratory liver abnormalities, but 3 of 6 animals had minimal histologic evidence of VOD. Three of 6 dogs in group 3 receiving 36 Gy developed hepatic dysfunction and had findings of fibrosis at autopsy. It was concluded that MC administration produced consistent clinical and histologic features of VOD in dogs. Changes occurring after busulfan or total-liver irradiation administration were less reproducible. Dogs are a suitable large animal model for studies of VOD. PMID- 1631921 TI - Rapid and long-term changes to host cytotoxic T lymphocyte precursors reactive to donor antigens caused by intravenous injection of histoincompatible lymphocytes. AB - It has been shown previously that a single intravenous injection of mouse F1 LNC into either parent results in a rapid reduction in the ability of the recipient to generate CTL reactive against donor antigens in an in vitro MLR. The underlying mechanism appears to be the inactivation of host CTL precursors that can recognize donor lymphocytes that have entered the recirculating pool. The donor lymphocytes may be acting as functionally deleting APC, or veto cells. Here, we have injected C57BL/6 (B6) mice with (C57BL/6 x DBA/2) F1 (F1) LNC. The CTL response against donor LNC was maximally reduced by 2 days and stayed reduced for at least 6 weeks, but ultimately recovered to normal levels. The response reduction mechanism remained operative during the period when the response was reduced: Fresh FITC-labeled B6 LNC introduced into B6 recipients of an earlier injection of F1 LNC were as effectively deleted of F1-reactive CTLp as the original host B6 LNC population, the fresh FITC-labelled B6 LNC being separated from host B6 LNC by cell sorting before testing. When B6 mice injected with F1 LNC ultimately recovered their response against F1 donor antigens, reinjection of F1 LNC did not induce a new response reduction. Instead of entering the recirculating pool, the injected F1 cells were rapidly removed by a specific immune process. PMID- 1631922 TI - The effects of donor-specific blood transfusion enhancement of rat renal allografts on host NK cell responses. AB - Donor-specific blood transfusion (DSBT) given 1-2 weeks prior to transplantation prolongs the survival of fully allogeneic ACI (RT1a) renal allografts in PVG (RT1c) recipients from 6-8 days to greater than 100 days. We have previously demonstrated that ACI kidneys transplanted to autologous blood transfusion (ABT)- or DSBT-pretreated PVG recipients stimulated an increase in CD8+ (OX8+) cells in the peripheral blood by 6 days after transplantation. To determine whether this increase represents a general expansion of the entire CD8+ population or only a subpopulation of CD8+ cells, subset analysis was performed on peripheral blood lymphocytes depleted of cells reactive with monoclonal antibodies against rat alpha beta T cell receptor (TCR), CD8, or NK cells (R7.3, OX8, or 3.2.3, respectively). Phenotypic studies of PBL depleted of CD8+ cells demonstrated that all 3.2.3+ NK cells coexpressed CD8; depletion of 3.2.3+ PBL revealed a second subpopulation of CD8+3.2.3- cells comprised predominantly of alpha beta TCR+ T cells. In naive PVG rats the prevalence of these two CD8+ subpopulations was approximately equal. Both ABT- and DSBT-pretreated renal allograft recipients demonstrated a significant and equivalent expansion of the CD8+ cell subpopulation that coexpresses the 3.2.3 NK marker. In contrast, the second subpopulation of CD8+3.2.3- cells did not change significantly after allografting. There were also no differences between DSBT and ABT pretreated rats in activity of PBL against the NK targets YAC-1 and Doxie at 6 days after renal transplantation, though the level of activity was modestly increased compared with naive controls. These findings indicate that renal transplantation in the rat is associated with a significant increase in PBL with the NK phenotype (CD8+3.2.3+) and a modest increase of NK activity, but that DSBT enhancement does not affect this NK cell response. PMID- 1631923 TI - Prevention of acute lethal graft-versus-host disease in F1 hybrid mice by pretreatment of the graft with anti-NK-1.1 and complement. AB - We studied the effect of depleting NK1.1+ cells from an allograft of lymph node and spleen cells on the outcome of GVH disease in the parent----F1-hybrid combination C57BL/6----(C57BL/6xDBA/2)F1. Four treatment groups were established: group I mice were transplanted with an unmodified graft from normal donors; group II mice were transplanted with an NK1.1-depleted graft that had been harvested from normal donors; group III mice received grafts from donors that had been injected with Poly I:C (100 micrograms i.p.) 18 hr prior to harvesting (These grafts were incubated with complement, but no antibody.); group IV mice were transplanted with depleted grafts harvested from donors that had received Poly I:C. Recipients in each group were monitored for splenomegaly, mitogen responsiveness, NK and CTL activity, histopathology, weight loss, and mortality. Results showed that recipients in all four groups developed splenomegaly and unresponsiveness to LPS, PHA, and Con A by day 12. Augmented host-derived NK activity and graft-derived antihost CTL activity was also demonstrated. Group IV showed little or no weight loss, minimal histopathological changes and a marked reduction in mortality. Recipients in all other groups developed features characteristic of GVH disease and exhibited a steady decline in body weight beginning by day 12. Mortality generally began on day 18 and reached 75-90% by day 60. We postulate that anti-NK1.1 depletes cells from the graft are intimately connected with the effector mechanism in acute GVH disease. PMID- 1631924 TI - Factors contributing to long-term kidney graft survival in Eurotransplant. AB - We examined the graft survival of 12,883 first unrelated kidney grafts from nonliving donors, transplanted between 1 January 1971 and 31 December 1987 within 52 renal transplantation centers participating in the Eurotransplant organization. The 5-year graft survival increased from 38.8% for the period 1971 1975 to 66.0% for the period 1981-1987 for patients treated with cyclosporine, whereas the half-life increased by only 2 years, from 9.7 years to 11.6 years over the same period, based on grafts functioning at 1 year posttransplantation. Results per HLA locus showed considerable improvements within mismatch groups over the entire period. Large differences between mismatch groups for the early years were observed, but within the cyclosporine era only HLA-B showed a statistically significant difference in half-lives (13.2 versus 9.0 years, for 0 and 2 mismatches respectively, P = 0.013). When other prognostic factors were taken into account, it was revealed by means of an exponential model that number of HLA-B mismatches, donor and recipient age and sex, and recipient diagnosis of diabetes had significant effects on the long-term outcome of the grafts. Depending on the combination of these parameters, estimates of half-life varied from 4.9 to 14.5 years. These results show that matching for HLA-B is still of benefit in the longer term and that other prognostic factors play an important role in predicting the late outcome of renal allografts. PMID- 1631925 TI - Successful renal transplantation after cyclosporine-associated hemolytic-uremic syndrome following bilateral lung transplantation. PMID- 1631926 TI - Reinstitution of immunosuppression in a renal transplant recipient after remission of Kaposi's sarcoma. PMID- 1631927 TI - Use of indomethacin to minimize the adverse reactions associated with orthoclone OKT3 treatment of kidney allograft rejection. PMID- 1631928 TI - Prevalence of dyslipidemia in liver transplant recipients. PMID- 1631929 TI - Differential effects of preexisting uremia and a synchronous kidney graft on pancreas allograft functional survival in rats. AB - Pancreas transplant results have been better in uremic recipients of a simultaneous kidney than in nonuremic recipients of a pancreas alone. We studied the relative effect of uremia versus a double transplant on functional survival by performing bladder-drained pancreas transplants alone (PTA), kidney transplants alone (KTA), and simultaneous pancreas/kidney (SPK) transplants from Buffalo donors to diabetic Lewis rat recipients that were or were not made uremic 2-3 weeks before by 1 4/5 native nephrectomy. Pancreas graft exocrine function was monitored by urinary amylase (UA). In the PTA and SPK recipients made diabetic by streptozotocin, endocrine function was monitored by measuring nonfasting plasma glucose (PG) levels. Kidney graft function was monitored by plasma creatinine (Cr). Rejection of the endocrine pancreas was defined as an increase of PG to greater than 200 mg/dl; of the exocrine pancreas, as a decline in UA to less than 6000 U/L or to less than 100 U/24 hr; and of the kidney, as an elevation of Cr to greater than 3 mg/dl. The mean functional survival times (MST) of both the endocrine (12.0 +/- 2.1 versus 10.1 +/- 1.1 days, P = 0.036) and exocrine (8.0 +/- 2.1 versus 6.3 +/- 1.3 days, P = 0.016) components of the pancreas grafts were significantly longer in SPK than in PTA recipients. The MST of kidney allografts, however, was not significantly longer in nonuremic SPK than nonuremic KTA recipients (6.7 +/- 1.4 versus 5.7 +/- 0.7 days, P = 0.13). In parallel experiments in recipients immunosuppressed with cyclosporine, the graft survival times were longer, but the relative differences between the PTA, SPK, and KTA groups persisted. Histologically, lymphocyte infiltration began in the two organs almost simultaneously, but the severity of the rejection was more vigorous in the kidney than in the pancreas in doubly grafted rats, and destruction of pancreas grafts progressed more slowly in SPK than in PTA recipients. Preexisting uremia delayed pancreas rejection in both SPK (exocrine 10.6 +/- 2.3, P = 0.032, and endocrine 14.8 +/- 3.4 days, P = 0.065, versus nonuremics) and PTA (exocrine 8.5 +/- 1.7, P = 0.007, and endocrine 12.6 +/- 2.5, P = 0.026, versus nonuremics) nonimmunosuppressed recipients. The MST of kidney grafts was not significantly longer in uremic (8.9 +/- 2.8 days) than in nonuremic (6.7 +/- 1.4 days) SPK recipients (P = 0.081). A synchronous kidney transplant and uremia independently down-modulate the rejection response to a pancreas graft, and a simultaneous pancreas graft has no detrimental effect on the survival of a kidney graft.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1631930 TI - Relevance of the nutritional status of donors in viability of transplanted hepatic allografts. PMID- 1631931 TI - Intraoperative color Doppler ultrasonography for partial-liver transplantation from the living donor in pediatric patients. PMID- 1631932 TI - Oxygen free radical-mediated lipid peroxidation injury in acute cardiac allograft rejection. PMID- 1631933 TI - A modified vascular "sleeve" anastomosis for rearterialization in orthotopic liver transplantation in rats. PMID- 1631934 TI - The role of reduced glutathione in heart preservation using a polyethylene glycol solution, Cardiosol. PMID- 1631935 TI - Protection of pig liver against normothermic ischemia by immunosuppressants cyclosporine and azathioprine. PMID- 1631936 TI - Tissue-specific differentiation of a natural killer cell subset in ectopically grafted murine uterine tissue. PMID- 1631937 TI - Prolongation of skin allograft survival in mice by didemnin B. PMID- 1631938 TI - The effect of transplanting donor spleen with an organ allograft. PMID- 1631939 TI - The combi-effect with regard to pancreas grafts that include the donor spleen. PMID- 1631940 TI - Evidence that 15-deoxyspergualin inhibits natural antibody production but fails to prevent hyperacute rejection in a discordant xenograft model. AB - Preventing hyperacute rejection (HAR) is a difficult and unsolved problem in xenotransplantation. This may be due, in part, to a lack of therapies that can suppress production of natural antibodies (NA), which are thought to be critical mediators of HAR. This study examined the effect of 15-deoxyspergualin (DSPG) and splenectomy (Spx) on NA production and return of NA after plasma exchange (PE) in a discordant species combination (strain 2 guinea pig to Lewis rat). A dose of 5 mg/kg/day DSPG + Spx significantly reduced Lewis rat anti-guinea pig NA titer after one week of therapy. Antibody titer was not significantly reduced in rats treated with splenectomy alone. PE alone acutely depleted NA titers; however, complete rebound was seen in 48 hr. When PE was performed in rats treated with DSPG + Spx, an additional significant NA reduction occurred; no rebound 24-48 hr after PE was seen. Except for a 20% reduction in body weight, no serious complications occurred in DSPG + Spx recipients. Despite a profound NA titer reduction, treatment with DSPG, Spx, and PE did not prolong guinea pig cardiac xenograft survival in a clinically significant fashion. Immunopathological study of rejected cardiac xenografts revealed no antibody deposition but persistent complement deposition on vascular endothelium. We conclude that DSPG + Spx effectively inhibits synthesis of rat anti-guinea pig NA, that further NA titer reduction can be achieved with the addition of PE, and that DSPG + Spx prevents post-PE antibody rebound. We also conclude that the limited prolongation in cardiac xenograft survival achieved, despite marked suppression of NA, supports a complement-mediated mechanism of HAR in our animal model. PMID- 1631941 TI - The role of ultraviolet B-irradiated leukocyte transfusions and cyclosporine in intestinal transplantation. AB - To explore the efficacy of ultraviolet B-irradiated donor-specific leukocyte transfusions (UV-DSLT) with short-term cyclosporine to control intestinal allograft rejection, 75 adult Lewis (RT1l) rats underwent total small-intestinal transplantation from Brown-Norway (RT1n) donors. Recipients were randomly divided into ten treatment and control groups utilizing various combinations of donor specific and third-party (Wistar-Furth, RT1u) leukocyte transfusions (TPLT), with or without transfusion UVB irradiation, and either alone or in combination with short-term cyclosporine administration (5 mg/kg intramuscularly on days -7, 0, 1, and 2 relative to transplantation). Leukocytes (10(8) cells) separated from a spleen cell suspension were infused on day -7. Certain transfused leukocytes were treated with 12,000 joules/m2 of UVB irradiation. Groups were monitored for mean survival time (MST) and cause of death. UV-DSLT alone (MST = 19.8 +/- 4.6) or in combination with cyclosporine (UV-DSLT+CsA, MST = 53.1 +/- 22.5) significantly (P less than 0.003-0.0002, Mantel-Cox) prolonged recipient survival when compared with appropriate controls (i.e., no treatment, MST = 11.2 +/- 3.4; CsA, MST = 17.2 +/- 9.0; UV-TPLT, MST = 12.4 +/- 4.0; and UV-TPLT+CsA, MST = 25.1 +/- 9.7) No significant increase in graft-versus-host disease occurred in any group, with 85% (64/75) of the recipients dying of acute rejection. Conversely, the UV DSLT+CsA group had a significant increase (9/11; chi-square, P less than 0.0001) in chronic rejection. Because UV-DSLT+CsA improved survival as compared with third-party controls, a limited donor-specific unresponsiveness may have been induced. Furthermore, this treatment produces a consistent, chronic rejection rodent intestinal allograft model. PMID- 1631942 TI - Patterns of corneal graft rejection in the rabbit and reversal of rejection with monoclonal antibodies. AB - The purpose of this study was to determine whether the local administration of monoclonal antibodies could reverse rabbit corneal graft rejection. To provide a rational basis for the choice of monoclonal antibodies as potential immunosuppressive agents, the phenotypes of cells infiltrating rejecting rabbit corneal allografts were examined by immunohistochemistry. About half the leukocytes accumulating in these grafts bore an immunodominant T cell marker, over two-thirds carried MHC class II antigens, and about one-fifth carried myeloid cell markers. A kinetic study of the cell population appearing in rabbit aqueous during corneal graft rejection was performed by examination of repetitive anterior chamber taps taken over a ten-day period; again, the major components were T cells, MHC class II antigen-positive cells and myeloid cells. Monoclonal antibodies L11/135 (directed against a peripheral T cell determinant), 2C4 (directed against a monomorphic MHC class II antigen), and LION 2 (directed against a myeloid antigen) were chosen for intracameral injection into rabbits with rejecting corneal grafts. Each animal received a total of 50-100 micrograms of antibody in two injections at 3-4-day intervals. L11/135 and LION 2 reversed rejection in 5/9 and 8/12 animals, respectively, in the absence of any other immunosuppression; 2C4 was without effect. We suggest that monoclonal antibody therapy in corneal transplantation deserves further attention. PMID- 1631943 TI - Beneficial effect of combined 3,5,3'-triiodothyronine and vasopressin administration of hepatic energy status and systemic hemodynamics after brain death. AB - The influence of combined replenishment of L-3,5,3'-triiodothyronine (T3) and vasopressin (antidiuretic hormone [ADH]) on both hepatic metabolism and systemic hemodynamics was assessed in brain-dead dogs. Arterial ketone body ratio (AKBR) was measured as a parameter of hepatic metabolism, which reflects the redox state (free nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide) of liver mitochondria. Mean arterial blood pressure (MAP) was significantly decreased from 110.4 +/- 3.8 to 44.4 +/- 1.7 mmHg, at 1 hr after completion of brain death (P less than 0.01). In the control group AKBR was maintained thereafter at near control value of 1.0 with a significant decrease in serum lactate concentration in spite of marked hypotension. T3 infusion at a rate of 1 microgram/kg/hr elevated the AKBR but did not elevate MAP. Vasopressin infusion at a rate of 0.1 U/kg/hr sustained AKBR and elevated MAP significantly at 1 hr after administration but tended to decrease thereafter. Combined administration of T3 and ADH elevated the AKBR to about 2.0, and MAP was restored to near-normal level. Other parameters such as glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactic dehydrogenase, reflecting liver cell injury and serum creatinine, and blood urea nitrogen as renal function, were maintained within normal range. These results indicate that combined T3 and vasopressin administration has a beneficial synergistic effect on both hepatic energy metabolism and systemic hemodynamics without any detrimental influence to other conventional parameters. Therefore, it is suggested that this combined administration may contribute to the management of potential multiorgan donors. PMID- 1631944 TI - Sequential therapy--a prospective randomized trial of MALG versus OKT3 for prophylactic immunosuppression in cadaver renal allograft recipients. AB - We prospectively studied the use of prophylactic Minnesota antilymphocyte globulin vs. OKT3 in kidney transplant recipients. Between 7/1/87 and 9/1/90, 138 adult kidney and 35 kidney-pancreas recipients were randomized after stratification for age (18-49 vs. greater than or equal to 50), diabetes (diabetic vs. nondiabetic), transplant number (1 vs. greater than 1) and, for retransplants, the length of survival of the first graft (less than 1 year vs. greater than or equal to 1 year), and then randomized to receive 7 days of either MALG (20 mg/kg/day) or OKT3 (5 mg/day). Immunosuppression was otherwise identical in both groups; prednisone and azathioprine started on the day of surgery, and cyclosporine started on postoperative day 6. Minimum follow-up was 9 months. There was no difference in one- and two-year actuarial patient or graft survival rates, incidence of rejection, or serum creatinine level. MALG was associated with a higher incidence of cytomegalovirus; it was statistically significant in the subgroup of CMV seronegative recipients of kidneys from seropositive donors (P less than .05). OKT3 was more expensive and was associated with significantly more side effects: fever (P less than .0001), dyspnea (P = .04), and acute respiratory distress syndrome (ARDS) (P = .02). PMID- 1631945 TI - Daily renal hypoperfusion induced by cyclosporine in patients with renal transplantation. AB - A variety of side effects are associated with the use of cyclosporine, the most relevant of which remains the renal toxicity. We did parallel studies on cyclosporine pharmacokinetics and renal function in patients who had a recent kidney transplant and were given cyclosporine as a part of their immunosuppressive therapy. Seven consecutive renal transplant patients were studied at the end of a month of treatment while on different oral cyclosporine doses (5, 3.5, 2.5, or 1.5 mg/kg, twice a day, respectively). Cyclosporine pharmacokinetics profiles and renal function parameters (GFR and renal plasma flow [RPF], as inulin and p-amino hippurate clearances, respectively) were determined before and over a 12-hr period after each single dose of cyclosporine. Plasma levels and urinary excretion rate of endothelin were also studied before and after the highest cyclosporine dose (5 mg/kg). Mean trough levels, area under the curve values, and maximum concentration of blood cyclosporine were comparable after 5 and 3.5 mg/kg cyclosporine and decreased in a dose-dependent manner after the lower doses (2.5 and 1.5 mg/kg). In the same patients GFR declined on average 63%, 53%, 35%, and 18%, 2-4 hr after maximum cyclosporine concentration was reached. As blood levels of cyclosporine returned to trough, GFR progressively increased to baseline. Similar results were found for RPF; 5 mg/kg cyclosporine did not modify endothelin plasma levels. By contrast, urinary excretion of the peptide increased significantly (P less than 0.01) in the 6 hr that followed cyclosporine administration and returned within the normal range in the subsequent 6 hr. Following each oral administration of cyclosporine, 2-4 hr after peak blood concentration was reached, patients showed renal hypoperfusion, transient and rapidly reversible. This was associated with an increased urinary endothelin excretion rate that was also transient. It is speculated that an excessive renal synthesis of endothelin is the cause of the daily renal hypoperfusion observed in patients with renal transplants given cyclosporine. PMID- 1631946 TI - Hyperacute and acute kidney graft rejection due to antibodies against B cells. AB - Because of the perception of its uncertain clinical significance, the B cell crossmatch is not universally performed before renal transplantation. Even though sporadic cases of hyperacute rejection associated with B cell antibodies have been reported, doubts remain in light of other studies suggesting no effect on graft survival. This report describes 4 cases of graft rejection (3 hyperacute and 1 acute) that occurred in patients with anti-B-cell antibodies specific against donor HLA-DR or DQ antigens. Absence of anti-donor class I antibodies was confirmed in all cases by 2-color flow cytometry. Strong evidence for an antibody mediated mechanism was found in one patient with anti-class I and anti-class II antibodies in serum transplanted with a class II mismatched kidney. In this case, only anti-class II antibodies were recovered in the eluate of the nephrectomy specimen. These four cases were compiled from three different institutions over a four-year period, which confirms the infrequent occurrence of these events. While anti-class II antibodies may not always be detrimental for graft survival, these results also confirm that they have the potential to cause hyperacute or acute graft loss. We conclude that the information provided by the B cell crossmatch should be available at the time that a decision to proceed with a renal transplant is made. PMID- 1631947 TI - The efficacy and tolerability of cyclosporine G in human kidney transplant recipients. AB - Twelve consecutive first cadaveric kidney transplant recipients received cyclosporine G (CsG)(initial dose 12 mg/kg per day) as basic immunosuppressive treatment along with prednisone (initial dose 0.5 mg/kg per day) for the first three months after transplantation. Thereafter CsG was replaced by Sandimmun (cyclosporine, CsA). Evaluation of the immunosuppressive efficacy and assessment of possible side effects of CsG was made and compared with the results in 38 historical control patients starting with the same dose of CsA as part of the same immunosuppressive dosage schedule. Statistically, there was no difference in patient survival at three (91% in CsG group versus 95% in CsA group) and twelve months (91% in CsG group versus 92% in CsA group), or in graft survival at three (75% in CsG group versus 89% in CsA group) and twelve months (75% in CsG group versus 84% in the CsA group). At equivalent oral doses of CsG and CsA significantly higher blood levels of CsG were observed (2P less than 0.05). Nephrotoxicity assessed by graft biopsy could be demonstrated to a similar extent in both groups, whereas hepatotoxicity was more pronounced during CsG treatment. Sequential measurements of bilirubin revealed a significant increase in all patients but median values were significantly higher in the CsG patients. A pronounced and concordant elevation of liver enzymes occurred during CsG treatment in three out of 12 patients. Liver biopsies performed in these patients revealed histological alterations consistent with toxic liver injury. Thus, in human kidney transplant recipients CsG and CsA appeared to be equally immunosuppressive and nephrotoxic but more hepatotoxic. On the basis of this limited experience we conclude that in human kidney transplant recipients CsG has no advantage over CsA. PMID- 1631948 TI - Renal hemodynamics, urinary eicosanoids, and endothelin after liver transplantation. AB - Patients with hepatic cirrhosis develop widespread abnormalities in kidney function and vasoactive hormones. These change rapidly after liver transplantation during immunosuppression with cyclosporine. The role of changing eicosanoid excretion and endothelin levels in regulating renal function after transplantation in humans remains uncertain. We studied 32 patients with regard to renal hemodynamics, glomerular filtration, urinary prostacyclin (6-keto-PG-F1 alpha), thromboxane (TBX2), and endothelin before and during the first four weeks after orthotopic liver transplantation. Arterial pressure rose from 106 +/- 2/61 +/- 2 to 146 +/- 4/81 +/- 2 mmHg, (P less than .001), while renal blood flow fell (686 +/- 38 to 453 +/- 24 ml/min/1.73 m2, P less than .05), as did GFR. Pretransplant excretion of 6-keto and TBX2 was above that of normal subjects and fell progressively after transplant, as did plasma renin activity and aldosterone. The 6-keto levels fell below normal after two weeks. The ratio of TBX2/6-keto remained elevated compared with normal subjects throughout the month after transplant (1.54 +/- 0.38 vs. 0.54 +/- 0.07, P less than .01). Endothelin levels rose during the first week (7.4 +/- 1.4 vs. 12.4 +/- 2.7 pg/ml, P less than .05), but fell back to baseline thereafter. These results indicate that high levels of urinary eicosanoids in patients with liver disease fall rapidly after liver transplantation during CsA immunosuppression. Unlike results in many experimental models, these data suggest that renal vasoconstriction in humans may be associated primarily with suppression in renal prostacyclin excretion rather than stimulation of thromboxane. PMID- 1631949 TI - The failure of venovenous bypass to prevent graft liver postreperfusion syndrome. AB - We studied 58 patients undergoing orthotopic liver transplantation, aged 42 +/- 10 years (mean +/- SD), and weighing 65 +/- 14 kg. Anesthesia was maintained with fentanyl, midazolam, and vecuronium. Serum bicarbonate, serum potassium, serum ionized calcium and pH did not change significantly throughout the study. Usual hemodynamic parameters were recorded. Hemodynamic tolerance was assessed by a trial of clamping of the inferior vena cava, above and below the liver and the portal vein; patients were allocated to two groups: the group without venovenous bypass (NBP, n = 29) consisted of patients whose MAP did not decrease by more than 30% and/or cardiac output did not decrease by more than 50%; the group with venovenous bypass (BP, n = 29) consisted of patients whose MAP decreased by more than 30% and/or cardiac output decreased by more than 50% or required venovenous bypass for easier surgical dissection. After clamping of the vena cava and the portal vein, the cardiac index (CI) and mean pulmonary arterial pressure (MPAP) decreased significantly, whereas systemic vascular resistances (SVR) increased. After unclamping the inferior vena cava suprahepatically and infrahepatically, no hemodynamic change was observed. After unclamping the portal vein, MAP decreased, despite the increase in the CI, because of an significant decrease in SVR; in addition MPAP increased despite the decrease in pulmonary vascular resistances. The decrease in MAP of more than 30% during at least 1 min occurred in 6 patients (20%) in the NBP group and in 6 patients (20%) in the BP group. We concluded that the occurrence of the syndrome of cardiovascular collapse following liver reperfusion was similar whether venovenous bypass was used or not. PMID- 1631950 TI - The decrease in organ donations from 1985 to 1990 caused by increasing medical contraindications and refusals by relatives. AB - After the progressive improvement in the results of organ transplantation we now face the challenge of shortage in organ supply. The decreasing number of organ retrievals performed in 1990 at our hospital has raised questions concerning loss of potential organ donors and opposition to donation by the next of kin. We investigated these questions and the number of organs available per million inhabitants in the area covered by our university hospital. Our surgical intensive care unit provides about 85% of all organ donations for this area. To this end, all 375 deaths occurring in the surgical ICU during the period between January 1, 1985 and December 31, 1990 were analyzed. Of 138 brain-stem deaths, 43 presented medical contraindications preventing organ harvesting for transplantation. Consent for donation was sought from the families of the 95 remaining potential donors and was refused for 17 patients. Organ retrieval followed all of the 78 agreements to donate, so that no suitable donor was lost. Over the 6 years surveyed, a progressive decrease in organs procured was observed, due to an increase of medical contraindications to organ harvesting for transplantation (P less than 0.001) and a higher rate of refusals to donate organs (P less than 0.002). The rate of kidney retrieval was thereby reduced from 45 to less than 25 per million population per year between 1985 and 1990 for our hospital's catchment area. The reasons cited by the families for denying organ donation suggest that the publicity campaigns aimed at the medical community and the public concerning organ transplant programs should be modified, and that a careful selection of indications for transplantation seems mandatory. PMID- 1631951 TI - Regulation of antibody response by an IgG-anti-Ig autoantibody occurring during alloimmunization. I. A few IgG molecules inactivate one B cell. AB - We have shown previously that alloimmunized rats develop a broadly reactive IgG antiimmunoglobulin autoantibody in addition to antidonor antibodies. The findings presented herein demonstrate that this "physiological" antibody suppresses antigen receptor-induced IgM production of B cells derived from rats of the same strain. When affinity-purified IgG-anti-Ig was added to cell cultures, the antibody production of B cells was maximally inhibited at the minute concentration of 0.9 pg/10(6) cells. Higher or lower IgG-anti-Ig concentrations resulted in weaker suppression. The same result was obtained when spleen lymphocytes were used instead of purified B cells. Based on the molecular weight of IgG and Avogadro's number, our results indicate that a few molecules of IgG anti-Ig are sufficient to inhibit the antibody production of a single B cell. Activity at this minuscule concentration demonstrates that IgG-anti-Ig antibodies are exquisitely active immunoregulatory molecules. In addition to the stimulatory effect of IgM-anti-Ig rheumatoid factors reported by others, our findings define the second component of an immunoregulatory mechanism: suppression of the B cell response by an IgG-anti-Ig autoantibody produced during alloimmunization. PMID- 1631952 TI - Regulation of antibody response by an IgG-anti-Ig autoantibody occurring during alloimmunization. II. Selective inactivation of antigen receptor-occupied B cells. AB - Heterologous antiimmunoglobulin antibodies are efficient regulators of the B cell response. We have shown that during the immune response against allogeneic cells the immune system develops autologous IgG-antiimmunoglobulin. A few molecules of this "physiological" autoantibody suppress the IgM production of one B cell in vitro. In the current series of experiments we further define the regulation of antigen receptor-activated B cells by this autoantibody. To mimic the in vivo situation, where IgG-anti-Ig appears a few days after alloimmunization, the antibody's effect on an already ongoing B cell response was studied. Interestingly, we found that the IgG-anti-Ig loses its suppressive effect when added to the cell culture 1 or 2 days after B cell activation, but that suppression can be completely restored when the cells are restimulated via their antigen receptor. Thus, the IgG-anti-Ig antibody suppresses B cells only when their antigen receptor is occupied. Even restimulated B cells become refractory 8 hr after activation, and later (24 hr) regain their susceptibility to IgG-anti-Ig induced suppression. The Fc receptor is involved in mediating suppression since the antibody's suppressive capacity is abolished after removal of its Fc region. Possible mechanisms of B cell suppression by IgG-anti-Ig are crosslinking of antigen receptor with Fc receptor, or cocapping and functional interaction of the two receptors as a result of their separate occupancy. Our experiments demonstrate that B cell regulation by IgG-anti-Ig produced during an immune response to allogeneic cells is governed by 3 restriction mechanisms: antigen receptor occupancy, activation stage dependency, and optimal antibody concentration. PMID- 1631953 TI - Mouse mutations and human disorders are paired. PMID- 1631954 TI - Temporal regulation in the early embryo: is MBT too good to be true? AB - The question of how early embryonic events are temporally regulated has traditionally been tied to the mid-blastula transition (MBT). This concept has directed the studies in Xenopus and influenced the studies in other organisms. By examining the weaknesses in the concept of MBT, we hope to refocus the study of temporal regulation on the many developmental transitions that do exist and to clear the way for an alternative viewpoint that emphasizes the similarities between developmental processes in different organisms. PMID- 1631955 TI - Small repeated sequences and the structure of plant mitochondrial genomes. AB - The structure of plant mitochondrial genomes has proven to be complex and difficult to study. Recombination across large and small repeated sequences can result in genome diversity within individual plants, as well as rapid evolutionary change in genome structure. The role of these repeats is becoming more obvious as mitochondrial genomes are examined in detail. PMID- 1631956 TI - Hormones, puffs and flies: the molecular control of metamorphosis by ecdysone. AB - Pulses of the steroid hormone ecdysone during late larval and prepupal development in Drosophila coordinate the activation of a large number of primary and secondary response genes, signalling the onset of metamorphosis. Molecular characterization of some of these genes has provided valuable clues to regulatory mechanisms by which the ecdysone signal is transduced and amplified. PMID- 1631957 TI - The molecular basis of glucose-6-phosphate dehydrogenase deficiency. AB - With more than 300 different variants reported, the human enzyme glucose-6 phosphate dehydrogenase (G6PD; EC 1.1.1.49) is one of the most polymorphic proteins known. An estimated 400 million people throughout the world are deficient in G6PD; numerous lines of evidence indicate that this is because female heterozygotes have a selective advantage in malaria infections. The cloning of the G6PD gene has made it possible to clarify the molecular basis underlying this enzyme deficiency and polymorphism. PMID- 1631958 TI - The three eras of research in experimental toxicology. PMID- 1631959 TI - Metabolic polymorphisms affecting activation of toxic and mutagenic arylamines. PMID- 1631960 TI - Cytokines and eicosanoids in cancer drug toxicity. PMID- 1631961 TI - Anthranoid laxatives and colorectal cancer. PMID- 1631962 TI - Scientific discourse, in public. AB - The experience of writing for a wider audience has benefits and drawbacks. Attempting to make scientific issues more accessible to non-scientists is no easier than explaining them to peers. Indeed, explaining toxicological data such as solvent measurements from a hazardous waste site can be even more difficult, especially in addressing those living next to the site. Alastair Hay reconsiders his experience in two cases that brought toxicology under public scrutiny. PMID- 1631963 TI - Cell death by apoptosis and its protective role against disease. AB - The involvement of cell death in control of tissue growth has long been neglected, but the description of apoptosis as cellular 'suicide', the functional opposite of mitosis, is now attracting more attention to this phenomenon. Physiologically unwanted cells are removed by apoptosis, and toxic chemicals and drugs may enhance or inhibit this type of cell death. These findings are providing new insights into the pathophysiology of a variety of diseases, and suggesting new therapeutic strategies. PMID- 1631964 TI - Nuclear receptors and chemical carcinogenesis. AB - A number of non-genotoxic chemical carcinogens can recognize specific intracellular proteins. These cellular targets include members of the nuclear receptor family of ligand-activated transcription factors. Some non-genotoxic carcinogens appear to mimic the action of hormones and growth factors and perturb signal transduction pathways. Their carcinogenic activity may therefore result from the persistent stimulation of such pathways, promoting the growth of initiated cells. PMID- 1631965 TI - [Endovascular treatment of arteriosclerosis]. PMID- 1631966 TI - [Excimer laser-assisted balloon angioplasty of the femoro-popliteal segment]. AB - In the Department of Vascular Surgery RK, The University Hospital in Copenhagen, the authors have treated 16 patients with ischaemia in the lower limb by means of laser-assisted balloon angioplasty. A pulsed ultraviolet excimer-laser was employed. It proved possible to break down the occluding arterial lesion in 12 patients (75%). In one patient, this was not followed-up by balloon angioplasty and, in another patient, the reconstruction closed on the first day after operation. The primary success of the procedure, defined as breaking down of the occlusion with the laser-catheter followed by balloon angioplasty and an increase in the ankle/brachial index of greater than 15%, was found to be 10/16 or 62%. The remaining four patients, in whom it did not prove possible to break down the arterial lesion with laser, were treated by means of conventional vascular surgical reconstruction. On follow-up examination after an average of nine months, nine out of the ten patients (90%) still had a patent reconstruction after laser-assisted balloon angioplasty. This new endovascular laser-procedure appears to be suitable for selected patients, but must be assessed more meticulously before it is possible to determine its future placing in the vascular surgical therapeutic armamentarium. PMID- 1631967 TI - [Insulin resistance--a physiopathological condition with numerous sequelae: non insulin-dependent diabetes mellitus (NIDDM), android obesity, essential hypertension, dyslipidemia and atherosclerosis]. AB - Recent research has demonstrated that reduced insulin-stimulated glucose metabolism in skeletal muscle (insulin resistance) and hyperinsulinism are common features in widespread diseases such as essential hypertension, android obesity, non-insulin dependent diabetes mellitus, dyslipidemia (in the form of raised serum triglyceride and reduced serum high-density lipoprotein (HDL) cholesterol) and arteriosclerosis. Simultaneously, investigations in a comprehensive group of healthy middle-aged men have revealed insulin resistance in one fourth. On the basis of these observations, a working hypothesis is suggested which postulates that genetic abnormalities in one or more of the candidate genes in the modes of action of insulin occur in a great proportion of the population. These may result in insulin resistance (primary genetic insulin resistance). Primary insulin resistance may be potentiated by a series of circumstances such as ageing, high fat diet, lack of physical activity, hormonal and metabolic abnormalities or drugs (secondary insulin resistance). As a consequence of the reduced effect of insulin on muscle tissue, compensatory hyperinsulinism develops. Depending on the remaining vulnerability of the individual the hyperinsulinism is presumed to result in development of one or more phenotypes. For example if the beta-cells of the pancreas are unable to secrete sufficient insulin to compensate the insulin resistance on account of genetic defects, glucose intolerance will develop. In a similar manner, hyperinsulinism in insulin-resistant individuals who are predisposed to essential hypertension is presumed to reveal genetic defects in the blood pressure regulating mechanisms and thus contribute to development of the disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1631968 TI - [Emphysematous pyelonephritis. A serious complication of diabetes mellitus]. AB - Pyelonephritis emphysematous (PE) is a life threatening renal infection which is observed practically exclusively as a serious complication of diabetes mellitus. 95% of the 73 cases which have been reviewed were found in diabetic patients. The symptomatology resembles that of severe acute pyelonephritis but the disease differs from this in that, in PE, emphysema develops in the actual renal parenchyma and/or in the perirenal tissues. The most important single factor in the etiology appears to be ischaemia of the tissues which are employed as growth media for the microorganisms involved. Infections with E. coli, Klebsiella pneumoniae, Aerobacter and Proteus are the most commonly found. Isolated cases with Candida and Cryptococcus neoformans have been observed. The mortality in untreated cases of PE is 100%. With medical treatment alone, the mortality decreases to 73% while, when combined medical and surgical intervention is employed, the mortality can be reduced to 30%. PMID- 1631969 TI - [Methylmethacrylate and organic dementia. A dose-response analysis among dental technicians and opticians]. AB - The substance methylmethacrylate (MMA) is an organic solvent which is employed inter alii for prostheses which is suspected of being neurotoxic. With the object of illustrating whether there is a connection between exposure to MMA and symptoms of organic dementia, a cross-sectional investigation was carried out on a population consisting of occupationally active dental technicians and opticians (n = 528) and a group of dental technicians who were no longer occupationally active (n = 173). No noteworthy difference in the background variables, apart from age, was observed. Age was taken into consideration in the analysis. The results show a statistically significant increase in the prevalence of the chronic symptoms on increasing exposure. Where the acute symptoms are concerned, the connection is not statistically significant, but a tendency is observed. A chronic symptom index constructed on the basis of 13 questions concerning chronic symptoms is compared with the life exposure and the age. A statistically significant increase in the index was found with exposure to MMA, although not for the oldest age group. The pattern symptoms, presence of bias and other forms of exposure are discussed. It is concluded that this investigation confirms the hypothesis that symptoms of organic dementia have a connection the exposure to MMA. The results support the presumption that MMA causes acute and chronic damage to the central nervous system even with exposure below the safety limits. It is recommended that the occupational environment of dental technicians, including the present safety limits, should be revised. PMID- 1631970 TI - [Microbiology related to anal abscess complicated with fistula formation]. AB - The results of operative treatment of anal abscesses with reviewed retrospectively for a period of three years with the object of correlating the microbiological findings on culture from the abscess with the presence of a fistula. Patients who had not been controlled postoperatively were requested to attend for anal examination. Fistula were demonstrated in 27 out of 83 patients. No fistulae nor recurrences of abscesses were found in patients in whom only bacteria not derived from the intestine were cultured. Culture from an anal abscesses is thus of considerable prognostic value. PMID- 1631971 TI - [Emphysematous pyelonephritis]. AB - A case of emphysematous pyelonephritis (EPN) is described. EPN is a severe suppurative infection of the renal parenchyma and the perirenal tissue, characterized by intra-renal, and possibly perirenal, gas formation. This is a rare form of acute pyelonephritis. The condition is associated with a high mortality. Diabetic patients are particularly prone to the disease. The diagnosis is established with great certainty by computed tomography of the kidneys. The condition should be treated with an intensive combined medical-urological regimen with percutaneous nephrostomy guided by computed tomography or ultrasound should be performed. If no therapeutic response occurs, surgical incision and drainage or nephrectomy are recommended. In the present case of EPN, the medical treatment proved adequate. PMID- 1631972 TI - [Fatal emphysematous pyelonephritis]. AB - A man aged 46 years with diabetes mellitus was admitted with acute right-sided renal symptoms. Pyelonephritis emphysematous without concretions was found. The patient was treated with insulin, fluids, electrolytes and antibiotics and nephrostomy was performed and, subsequently, an internal JJ-catheter in the ureter. The symptoms disappeared and he was discharged on a low dosage of sulphamethizol. After the planned removal of the JJ-catheter, sepsis running a lethal course developed. This emphasizes the importance of adequate prophylactic antibiotic therapy in connection with interventions in the urinary tracts. PMID- 1631973 TI - [Diagnosis of pulmonary fibrosis]. PMID- 1631974 TI - [P-pills do not cause breast cancer]. PMID- 1631975 TI - [Plant thorn synovitis]. PMID- 1631976 TI - [The PC for down-loading, selection and storage of literature references]. PMID- 1631977 TI - [Cesarean section]. PMID- 1631978 TI - [Uterine rupture in Denmark during the period 1980-1987]. AB - A retrospective review was undertaken of 128 consecutive cases of rupture of the uterus during the eight-year period from 1 Jan 1980-31 Dec 1987. It was found that rupture of the uterus occurs most commonly after previous Cesarean section but that it may occur after other types of operation on the uterus. Rupture of the uterus does not occur in primiparae unless special conditions are present. Potent stimulation appears to involve a slightly increased risk for rupture of the uterus. A great proportion of the ruptured uteri occurred in women who had previously been submitted to Cesarean section on account of breech presentation as primiparae. In subsequent pregnancies, this resulted in three dead infants and four children with severe brain damage. PMID- 1631979 TI - [Monitoring and oxygen therapy during gastrointestinal endoscopy]. AB - Gastroenterological Societies in Britain and USA have published recommendations for sedation, monitoring and oxygen therapy during gastrointestinal endoscopy. No scientific basis for the introduction of recommendations such as these is, however, present as it has not yet been proved that hypoxaemia is responsible for morbidity and mortality on gastrointestinal endoscopy. The pathogenesis of the development of myocardial ischaemia during gastrointestinal endoscopy is considered by many to be the simultaneous arterial hypoxaemia but recent investigations suggest that tachycardia is a more important factor. The scientific data available at present in this field is not conclusive. Introduction of recommendations for monitoring and oxygen therapy during gastrointestinal endoscopy in Denmark should be delayed until elucidation of the mechanisms involved has been undertaken. PMID- 1631980 TI - [Angiomyolipomas in the kidney. A review]. AB - Renal angiomyolipomata are rare, benign hamartomata composed of various amounts of fat, smooth muscle and blood vessels. The tumours may have an extremely variable clinical presentation which may be difficult to distinguish from other renal disorders. By combining the use of ultrasound- and CT-scanning, it is possible to make a definite diagnosis thus obviating usually unnecessary nephrectomy. Only symptomatic tumours require treatment. The treatment is directed mainly towards preventing or stopping bleeding. In cases where intervention is considered to be indicated, embolization should be carried out if possible. Otherwise, the renal surgery should preserve as much of the kidney as possible. Nephrectomy is indicated only for uncontrollable life-threatening bleeding, tumours which involve the whole kidney or in the presence of simultaneous carcinoma. PMID- 1631981 TI - [Autologous fibrin glue--preparation and clinical use]. AB - Fibrin tissue adhesive is a tissue adhesive in which the two components are fibrinogen concentrate and a thrombin solution, respectively. In autologous fibrin tissue adhesive, the fibrinogen is prepared from the patient's own blood in contrast to the fibrin adhesive available commercially where the fibrinogen is prepared from pooled donor plasma. In 42 heart and lung operations, autologous fibrin tissue adhesive prepared by a new method was employed in which the fibrinogen is separated from the patient's own plasma by precipitation with ethanol. Either 44 or 88 ml blood was employed for concentration of the fibrinogen. This resulted in 2.5 ml and 4.9 ml fibrinogen concentrate which was mixed with 0.3 parts of thrombin solution containing calcium and aprotinin (fibrolysis inhibitor) so that the total volumes of tissue adhesive were 3.3 ml and 6.4 ml. Production of autologous fibrin tissue adhesive is uncomplicated and takes less than 90 minutes. A new method of production of autologous tissue adhesive based on ethanol is described. The fibrin tissue adhesive prepared in this manner has a high concentration of fibrinogen and is effective as a haemostatic and as an adhesive in surgical operations and it has the further advantage that it is not associated with the risk of transmission of viral or for immunological reactions. PMID- 1631982 TI - [Bacterial degradation of fibrin glue in vitro]. PMID- 1631983 TI - [Measurement of anti-thyroid peroxidase antibodies as a substitute to measurements of microsomal and thyroglobulin antibodies]. PMID- 1631985 TI - [Continuous positive airway pressure (CPAP)--does the equipment live up to its name?]. AB - The purpose of this study was to evaluate the in- and expiratory pressures achieved by the use of different continuous positive airway pressure (CPAP) delivery systems. The study was performed on ten healthy adults breathing spontaneously with: 1) "simple CPAP", consisting of a fresh gas flow around 40 l/min and reservoir balloons of 2, 6 and 10 l and expiration against a water column, 2) a high-flow system CR60 CPAP, designed for home treatment and 3) another high-flow system Down's CPAP. Both high-flow systems used a venturi device (Downs Flow Generator, Vital Signs) giving flows around 90 and 170 l/min in our set-up, and the same PEEP valves (Vital signs) were used. All systems were tested with expiratory pressures set at 5, 10 and 20 cm H2O. Individual responses were found, but in general the simple CPAP with a 10 l latex balloon reservoir gave optimal CPAP. The high-flow systems were not found to provide better CPAP, however, CR60 CPAP was found also to be optimal with 5 and 10 cm H2O. Down's CPAP provided 3-5 cm higher expiratory pressure than the intended CPAP level. We recommend measurement of the pressure during the CPAP treatment to ensure that the intended CPAP is achieved. PMID- 1631984 TI - [Biological monitoring in chromium-plating industry]. AB - The purpose of the present investigation was to evaluate the role of biological monitoring as a means of surveillance of exposure in the Danish chromium-plating industry. We collected spot urine samples from 47 employees in five electro plating plants near Aarhus and compared the results wide 40 non-exposed workers. We found no increase of chromium in urine during a work shift (mean = 0.11 nmol chromium/mmol creatinine, p = .46). The mean urine chromium value among the chromium workers was twice the mean value of the referent population (p = 0.001). There was, however, a considerable overlap between the two populations. All of the urine chromium values were much lower than the proposed American biological exposure indices. The results do not indicate any need for implementation of biological monitoring in the Danish chromium-plating industry, but longitudinal studies concerning possible accumulation of chromium at present occupational exposure levels should be carried out. PMID- 1631986 TI - [Toxic shock syndrome after Cesarean section]. AB - A case of toxic shock syndrome (TSS) after caesarean section is reported. Strains Staphylococcus aureus (phage type 80/42E/81/83A--mixed type) producing toxic shock syndrome toxin-1 in very great grantities amounts were isolated from the surgical wound. The diagnosis is often difficult in non-menstrual cases in which TSS is not expected. PMID- 1631987 TI - [Epiphysiolysis in the distal femur as a birth injury in Cesarean section]. AB - A case of fracture-separation of the distal femoral epiphysis complicating cesarean section for delivery of an infant in breech presentation is described. Femoral fracture is a rare birth injury, particularly at cesarean section. The lesion can interfere with the growth of the bone, especially if overlooked. PMID- 1631988 TI - [Are better prenatal care and larger maternity wards the answer to the problem of stagnating perinatal mortality?]. PMID- 1631989 TI - [Ambulatory labors in the county of Ringkobing]. PMID- 1631990 TI - [Treatment of tubal dysfunction and secretory otitis media with a nasal balloon (Otovent)]. PMID- 1631991 TI - [Esophageal ECG and the pill electrode--one more time]. PMID- 1631992 TI - [Hemophilia--a commentary]. PMID- 1631993 TI - [Drug therapy of intermittent claudication]. PMID- 1631994 TI - [EDTA versus placebo treatment in intermittent claudication. A double-blind, randomized trial]. PMID- 1631995 TI - [Intermittent claudication]. AB - Intermittent claudication is a symptom triggered from the musculature during walking. The pathogenesis of the pain is unknown. All patients with peripheral vascular disease must abstain from smoking, perform physical exercise and dietary advice is sometime needed. Reconstructive vascular surgery or percutaneous transluminal angioplasty (PTA) are indicated when the occupational pattern and, in some instances, the recreational activities, are threatened. The results of these treatments are good. For various reasons a number of patients, however, cannot be offered these treatments. These patients must be informed of the importance of physical exercise and discontinuation of smoking. Some of these patients can be offered supplementary medical treatment (e.g. pentoxifylline). PMID- 1631996 TI - [Quality assurance of results of clinical chemical analyses in Danish hospital laboratories]. AB - During the past 35 years, voluntary professional assessment of quality of the results of analyses in Danish hospital laboratories has been undertaken under the auspices of the Danish Society of Clinical Chemistry. The analytical quality of the laboratories is described by their "imprecision" and "accuracy" as expressed by "coefficient of variation" and "bias", respectively. The participation in these programmes was 90%. During the period between 1968 and 1987, inter laboratory variation decreased markedly where all analyses were concerned. To ensure the necessary and adequate quality, establishment of specifications of quality based on clinical/biological goals of quality has proved necessary. The commonest reasons for large imprecision and bias from the target values are less specific methods of analysis, errors in calibration and sporadic "outliers". As the result of a stable organisation for ensuring quality, Denmark is well equipped for the introduction of the great demands in documentation of quality which may be anticipated from the Common Market during the immediate future. PMID- 1631997 TI - [Compositae dermatitis]. PMID- 1631998 TI - [Premature ejaculation--results of treatment of men of 2 different cultural backgrounds]. AB - The object of this investigation was to compare Danish and Muslim men treated for premature ejaculation in the Department of Sexology, Rigshospitalet, Copenhagen. The investigation is a retrospective review from the period 1986-1989. The following variables were included in the investigation: Mode of referral, personal data, duration of sexual dysfunction, previous sexological/psychiatric treatment, methods of treatment and results of treatment. The material consists of 60 Danish and 32 Muslim men. The investigation reveals that the Muslim men predominantly receive individual therapy of brief duration. Fewer Muslims were instructed in sensuality training and fewer carry out stop-start-treatment. The Muslim men responded more poorly to treatment than the Danish men. The differences in the therapeutic methods and therapeutic results cannot be explained on the basis of the personal parameters and possible cultural obstacles to treatment are suggested. For example, the therapist must become familiar with taboos and beliefs in the Muslim culture. The referring instance should inform the patients about the therapeutic principles at the Department of Sexology and attempts must be made to motivate possible partners to participate in the treatment. PMID- 1631999 TI - [Treatment of severe respiratory distress syndrome with surfactant]. AB - The first Danish experience of treatment of the respiratory distress syndrome (RDS) in preterm infants with exogenous surfactant is described. Fifteen infants with birthweights of 645-1,865 g and gestational ages of 25-32 weeks, all receiving artificial ventilation with at least 60% oxygen for severe RDS, were treated with purified porcine surfactant (Curosurf) within the first 28 hours of life. Pulmonary function improved immediately in all of the infants. Four infants (27%) died, four (27%) developed bronchopulmonary dysplasia (pulmonary fibrosis) and two (13%) had late neurological sequelae. These preliminary results are considered to be promising and they are in complete agreement with the results of randomised, controlled investigations from abroad. Systematic registration is, however, still necessary. PMID- 1632000 TI - [EDTA treatment of arteriosclerosis. Bias or manipulation?]. AB - A 62-year-old man suffering intermittent claudication had 20 infusions of EDTA in a double blind, placebo controlled trial. No effect on symptoms or systolic ankle/brachial blood pressure index was found. Following the trial, he received 30 further infusions of EDTA in a private clinic. The systolic ankle/brachial index was unchanged throughout the total period as measured in Hillerod Central Hospital. However, the private clinic found a significant increase in the index following EDTA treatment. The reason for this discrepancy could be poor technique in the clinic or it could be due to bias or manipulation. The discrepancy explains the difference between the positive results claimed by the private EDTA clinics and the results of the double blind placebo controlled Danish trial. PMID- 1632001 TI - [Reflex dystrophy after reconstruction of the axillary artery]. AB - Reflex sympathetic dystrophy (RSD) is a complex syndrome of pain, trophic changes and vasomotor instability affecting the limbs. Numerous theories have been suggested to explain the pathophysiology. None is universely accepted. In most of the patients reported, an antecedant event such as trauma or surgery is implicated in the initiation of symptoms. We describe a case of reflex sympathetic dystrophy developing after reconstruction of a. axillaris. To our knowledge there have only been a few previous descriptions of reflex dystrophy following vascular surgery. The mechanism of reflex sympathetic dystrophy secondary to vascular trauma is discussed. Presumely, damage to the arterial wall by trauma may initiate abnormal reflex activity and lead to RSD. We suggest that vascular surgery should be considered as a potential risk factor for the development of RSD. PMID- 1632002 TI - [Diagnosis of urinary tract infections and quality of diagnostic methods]. PMID- 1632003 TI - [Stomach ulcer and Helicobacter pylori]. PMID- 1632004 TI - [Helicobacter pylori]. AB - Helicobacter pylori (HP) are Gram-negative spiral bacteria which occur in the human stomach. The bacteria were cultured in vitro for the first time in 1983. It is suspected that the bacteria may cause chronic gastritis of type B and may also be a contributory cause of chronic ulceration and cancer of the stomach. The bacteria are accompanied by characteristic inflammatory changes in the gastric mucosa. The significance for gastritis, chronic ulceration, non-ulcer dyspepsia and carcinoma of the stomach is discussed. HP occurs in a great proportion of the population of the world and the frequency increases with age. The route of infection is unknown but faecal-oral infection is probable. Correlation between the presence of HP and the occurrence of symptoms is poor in the individual patient. The bacteria can be demonstrated histologically, cytologically, by culture, by the urease test, by the urease expiration test or serologically. The bacteria are sensitive for a series of antibiotics and bismuth but no effective treatment is known as the recurrence rate is high. PMID- 1632005 TI - [Testicular varicocele. Reason for surgery and recurrence frequency]. AB - In the period 1979-1989, 63 patients were operated on for testicular varicocele. The study was a retrospective follow-up from case records and from a questionnaire. Thirty-eight had local complaints, 19 were operated on because of infertility and six had an asymptomatic varicocele. 10% had minor, reversible complications. 92% answered the questionnaire and 38% had a personal contact. 21% had recurrence of the varicocele although to a minor degree. In the infertility group, 42% succeeded in conception after operation. PMID- 1632006 TI - [In-hospital day for patients connected with the District Psychiatric Center in Svendborg. A controlled study]. AB - As of 31.12.1990, the employment of bed-days and admissions was calculated for patients who had been connected with a district psychiatric centre for more than three years. A before-and-after comparison revealed a percentage reduction in the employment of bed-days as compared with a control group. This corresponds to the findings in other investigations. In the before-and-after analysis, various reductions are described according to the diagnostic groups. The reduction in bed day employment consisted mainly of fewer readmissions and reduction in the group of long-term hospitalisations. A reduction also occurred in the group of patients who could characterized as least ill. In this group, a marked percentage reduction in bed-days was observed as compared with the control group and this was probably due to the good and continuous treatment after discharge offered by the district psychiatric centre. This investigation revealed that the employment of bed-days for a patient population receiving district psychiatric treatment after discharge can be reduced. Nevertheless, the most severely ill patients will still require periodic admission to hospital. The value of treatment after discharge of the "Svendborg Model" type does not provide scientifically valid arguments that hospital admission can be avoided where the most severely ill patients are concerned. PMID- 1632007 TI - [Arteriosclerosis of the lower extremities--patients' contacts with alternative therapists]. AB - During the period July 1987-April 1988, ninety-one patients with arterial insufficiency in the lower limbs were referred to the Department of Thoracic and Vascular Surgery at Aalborg Hospital. The mean delay between contact with the general practitioner and the vascular surgeon was nine months. Twenty-nine of the patients contacted alternative therapists before referral to the vascular surgeon. Twenty-five of these patients had suffered from intermittent claudication for at least two years and the total cost of treatment was 76,013 Danish crowns (900 Danish crowns or approximately pounds 75 per patient). PMID- 1632008 TI - [Leprosy--still a possibility in Denmark]. AB - A case of borderline tuberculoid leprosy in a 27 year old woman from the Philippines is presented. The diagnosis was made after repeated biopsies. Only a single mycobacterium was present and the histology of the initial biopsies was inconclusive. This case emphasizes that leprosy is still imported to Denmark, and that the diagnosis is often difficult and delayed for years. PMID- 1632009 TI - [Pseudoporphyria]. AB - Pseudoporphyria with formation of bullae and vulnerability of skin exposed to light, particularly the backs of the hands, may be provoked medicinally by nalidixinic acid, tetracyclin, nabumeton, pyridoxine, dapsone and high-dosage furosemide and by excessive use of solaria. The present article demonstrates that the condition may also be precipitated by quinidine and ibuprophen. PMID- 1632010 TI - [What is the correct answer in the cholesterol debate?]. PMID- 1632011 TI - [Emotional side effects of Halcion; an unnecessary fear?]. PMID- 1632012 TI - [Are outpatient clinics for alcoholics an acceptable therapeutic possibility for all?]. PMID- 1632013 TI - [Sex differences among clients attending the outpatient clinic for alcoholics in the County of Vejle]. AB - A questionnaire investigation was undertaken in the four outpatient clinics for alcoholics in the County of Vejle in 1989. A total of 246 clients participated. The object was to illustrate differences and similarities between the sexes and aspects of the abuse. No differences were found as regards the frequency of unemployment and retirement or the housing conditions but the women were more frequently unemployed for 36 months or more. Where both sexes were concerned, the clients most frequently lived alone. The male clients had more frequently lost their employment, experienced failure of partnership, lost their driving licences or had been in detention on account of the abuse. Women were more frequently untrained, their incomes were lower, they had more frequently received public assistance and belonged most frequently to social group V. Women had more frequently children under the age of 16 years in the home and were more frequently alone with their children. Women had more frequently a partner who was addicted. Only women had children who had been placed under care. Women sought treatment earlier than men. The female clients thus appear to require particular attention and support because their social conditions, including those of their families, were, in general, worse than those of the male clients. PMID- 1632014 TI - [Social conditions of the clientele attending the outpatient clinic for alcoholics in the County of Vejle. A re-examination]. AB - A questionnaire investigation was performed among the clients attending the four outpatient clinics in the County of Vejle. The object of this investigation was to register aspects of the social conditions of 246 clients, to illustrate the present conditions and to observe changes as compared with previous conditions. The clientele attending outpatient clinics for alcoholics is still an extremely stressed group but, in several respects, the conditions are now better than previously. Nowadays, more of the clients had had prolonged school education and their earnings were relatively higher. Fewer clients lived in one room, fewer had received economic assistance, fewer were in social group V, fewer had come down in the world socially, and much fewer lived under extremely stressed circumstances. The clients lived most frequently alone. Nearly 40% had current or previous mixed addiction. Despite a relatively great number of new clients, the duration of addiction was now apparently longer to institution of treatment. Considerably fewer people under the age of 30 years now sought treatment in outpatient clinics for alcoholics. The authors consider that it is important that attractive offers of outpatient treatment of alcoholics are still available, one of the reasons being the possibility of altering the abuse as early as possible. PMID- 1632015 TI - [Changes in social conditions and drinking patterns in male and female clients attending an outpatient clinic for alcoholics in Copenhagen]. AB - The proportion of new female clients in the ALKO outpatient clinic in Copenhagen increased from 22% in 1975 to 37% in 1985. The first 100 new male and female clients in the ALKO outpatient clinic in 1975 and 1985 were investigated. The new female clients in 1985 were educated better as regards scholastic and occupational training than were the new female clients in 1975. Fewer of the clients of the ALKO outpatient clinic were married than was the case in the normal population in 1975 and also 1985. In 1975, fewer of the new female clients were registered in the occupational market than among the new female clients in 1985. Attention is drawn to a tendency to evening out of the differences between male and female alcohol addicts as regards social conditions and drinking patterns. The therapeutic consequences of these observations are discussed. PMID- 1632016 TI - [The laryngeal mask. An anesthesiological reevaluation]. AB - The larynx mask (LM) is an alternative to a mask and endotracheal tube. LM ensures free airway for the patient under anaesthesia while the anaesthetist has his hands free. The mask is introduced into the pharynx in the anaesthetized patient without use of muscle relaxants or laryngoscope. The literature is reviewed. The possibilities for employment are discussed and the authors' personal experience is presented. PMID- 1632018 TI - [The value of fine-needle aspiration cytology for a practising otologist]. AB - The results of 100 consecutive fine-needle punctures carried out in an otological practice are reviewed, discussed and compared with the literature. 93% diagnostic aspirates with negative predictive value of 0.97 and positive predictive value of 0.93 in histologically verified aspirates were obtained. It is concluded that fine-needle aspiration cytology is a very suitable method of investigation also in specialist practice. PMID- 1632017 TI - [Treatment of girls with Turner's syndrome with growth hormone and estrogen--1 year experiences]. AB - Girls with Turner's syndrome are characterized by growth retardation and defective pubertal development, among other features. In this investigation, 40 girls with Turner's syndrome were treated with growth hormone in doses of 0.1 IU/kg/day (group 1, n = 14), oral oestradiol in doses of 0.01 mg/kg/day (group 2, n = 8) or a combination of these (group 3, n = 18), depending on the bone age. All three forms of treatment increased the height velocity significantly. The combined treatment increased the height velocity more than the growth hormone of oestradiol alone (p less than 0.05). In group 2, a pronounced progression of bone age leading to a decrease in the prognosis of final height was observed. The serum insulin-like growth factor I was unchanged in group 2 while this rose in groups 1 and 3. Pubertal development was, by and large, satisfactory. No serious side effects were observed. Treatment of girls with Turner's syndrome with growth hormone should not be supplemented with oestrogen prior to the bone age of 11 years. The initial dosage of oestradiol should be less than 0.01 mg/kg/day, but the subsequent increase should be adjusted individually. PMID- 1632019 TI - [Difficult intubation--helped by a laryngeal mask]. AB - Two cases of difficult intubation are described in which the problem was overcome by use of the laryngeal mask airway. The anaesthetist should be thoroughly familiar with the technique before attempting to use it in difficult cases. PMID- 1632020 TI - [Appendiceal mucocele of unusual size]. PMID- 1632021 TI - [Benign pneumoperitoneum and scrotal emphysema after colonoscopy]. AB - A case of benign pneumoperitoneum and subcutaneous emphysema of the scrotum after elective colonoscopy with polypectomy is reported. The development and treatment of benign pneumoperitoneum is discussed. PMID- 1632022 TI - [The effect of psychotherapy]. PMID- 1632023 TI - [Therapeutic evaluation of psychotherapy]. PMID- 1632024 TI - [The HIV-positive surgeon]. PMID- 1632025 TI - [A method of combined horizontal resection of the larynx with removal of the arytenoid cartilage and its primary reconstruction]. AB - A modified technique of combined laryngeal resection in vestibular cancer T3-T4 (involvement of the arytenoid cartilage) was tried in 8 patients. To compensate for laryngeal separative function after the radical surgery, the reconstruction of the posterior laryngeal wall was performed by mobilization of the upper corniculum of the thyroid cartilage. In satisfactory functional results the method did not contribute to the disease aggravation. PMID- 1632026 TI - [Prognostic significance of the reaction of regional lymph nodes and lymphoid cellular infiltration of the tumor in laryngeal cancer]. AB - The immune response of the primary tumor and regional lymph nodes was studied morphologically in 239 patients with vestibular cancer of the larynx. Marked infiltration of the stroma developed in 48, mild response or its absence were recorded in 97 patients. The difference in 5-year survival was significant (84 versus 62%). Out of 117 patients examined for B-dependent cortical and T dependent paracortical response of the lymph nodes, 5-year survival in hyperplasia of the zones appeared to be 67%, in the absence of hyperplasia 42% and 44%, respectively. The difference is significant. The responses were essential for prognostication of the patient' survival. PMID- 1632027 TI - [Diagnostic significance of the study of lacrimal secretion in otorhinolaryngology]. AB - As shown by Schirmer's test of lacrimal secretion in 110 patients with peripheral paralysis of the facial nerve and in 35 patients with chronic polypous sinusitis subjected to vidiotomy, lacrimal secretion in both groups patients underwent marked changes. After dissection of the Vidian nerve a persistent decline in lacrimal secretion was universal, though preoperative tests in the peripheral paralysis patients displayed hyposecretion in 28 and hypersecretion in the rest cases. Nasolacrimal reflex investigation is recommended in obscure results of the Schirmer's test. PMID- 1632028 TI - [Intranasal dacryocystorhinostomy in children]. AB - Endonasal dacryocystorhinostomy performed in 78 children gave a steady favourable effect. Such a surgical operation is also recommended in dacryocysts complicated by phlegmons. Concomitant external fistulae of the lacrimal sac usually spontaneously closed after the operation, large fistulas were sutured. PMID- 1632029 TI - [A reliable symptom in differential diagnosis of cochlear and retrocochlear neurosensory hypoacusis (study of sound lateralization in Weber's test and ultrasound)]. AB - Sound laterality in Weber test occurs mainly in peripheral defects of the acoustic analyzer (lateral conduction or reception acoustic defects of the cochlea). In retrocochlear unilateral hypoacusis or loss of hearing, laterality in this test is absent in 80-90% of the cases (affection of the VIII nerve root, acoustic nuclei, stem and midbrain conductors). This symptom is most reliable in differentiation of cochlear with retrocochlear unilateral hypoacusis and deafness. In combination of retrocochlear hypoacusis of deafness with impaired sound conduction in the same ear, the sound in Weber test can show a paradoxical laterality in an absolutely deaf ear. This indicates that Weber test sound laterality definitely reflects changes in sound conduction. Ultrasound laterality occurs in the better hearing ear in any unilateral cochlear or retrocochlear lesions, thus complicating recognition of cochlear from retrocochlear affections. Laterality of ultrasound is a sensitive indicator of neurosensory abnormalities. Major trepanation bone defects of the parietotemporal skull did not influence sound laterality in Weber test. PMID- 1632030 TI - [Extracochlear prosthesis in acute experiment]. AB - Whether the transfer of coded sound intensity is possible was studied in acute experiments on cats with acquired deafness, using an original transducer of the signals with extracochlear position of the electrodes. The stimulation results were compared to intracochlear prosthesis. The type of the stimulation was not essential for threshold values of the total electric impact. In extracochlear position of the electrodes and the duration of potential 0.2 msec its amplitude increment was the highest, while the dynamic range turned out the lowest. With the impulse duration 0.5 msec, these differences disappeared. When compared to extracochlear, intracochlear bipolar stimulation proved superior. PMID- 1632031 TI - [Modulators of intracellular metabolism in the treatment of diseases of the internal ear]. AB - Stress reactions develop in different organs as a result of the effect of unfavourable factors which increase the differential threshold for men. These derangements mainly occur in the organs where we can observe an inadequacy between high level of metabolism in the cell and instability of energy supply. Under such conditions stress reactions in the cells have the following stages in succession: intensiveness of the lipolysis in mitochondria, accumulation in the cells of fatty acid metabolites, destruction of the membranous apparatus of the cells, increase in the presence of Ca++ in the cells. PMID- 1632032 TI - [Characteristics of the vestibulo-ocular relations in patients with lesions of the central regions of the vestibular system]. AB - Vestibular-ocular relations were studied in 30 patients with central vestibular affections varying in origin. Use was made of sinusoidal rotation with eyes closed and glance fixation tests. Symptoms of vestibular-ocular dysregulation typical for stem-cerebellar abnormalities were identified. PMID- 1632033 TI - [Use of local oxygenation and dimexide in the treatment of suppurative maxillary sinusitis in children]. AB - In search for high-efficacy therapy for childhood sinusitis, the author developed a unit providing a long-term perfusion followed by local oxygenation the maxillary sinuses. Intrasinus administration of 10% dimexide solution did not produce a negative effect on the ciliated epithelium. Out of 52 patients treated, cure within 2-year follow-up was achieved in 49 subjects. All the sufferers with maxillary sinusitis recovered. The disease relapsed in 5 cases. In control group treated by long-term drainage with local antibiotics recurrent inflammation was registered in 12 out of 52 cases. PMID- 1632034 TI - [Intranasal method of the diagnostic puncture of ethmoidal labyrinth cells]. PMID- 1632035 TI - [A device for game audiometry]. PMID- 1632036 TI - [Congenital retroauricular fistula]. PMID- 1632037 TI - [A penetrating wound of the skull with injuries of the brain, orbit and ethmoidal labyrinth]. PMID- 1632038 TI - [Marginal cholesteatoma of the mastoid process in a patient with chronic purulent otitis media]. PMID- 1632039 TI - [A rare case of brain tumor associated with acute purulent maxillary sinusitis with a course of rhinogenic intracranial complication in a pregnant woman]. PMID- 1632040 TI - [Association of otogenic meningoencephalitis and acute disorder of cerebral blood circulation]. PMID- 1632041 TI - [Angioleiomyoma of the retropharynx]. PMID- 1632042 TI - [Laryngeal stenosis in a child with congenital dysplasia]. PMID- 1632044 TI - [Case report of tracheal foreign bodies]. PMID- 1632043 TI - [Primary multiple cancer of the larynx and thyroid]. PMID- 1632045 TI - [A system for training otorhinolaryngology specialists]. PMID- 1632046 TI - [Otorhinolaryngologic complex of knowledge and skills in the training of family physician]. PMID- 1632047 TI - [Features of diagnosis and treatment of air cysts associated with different diseases of the larynx]. PMID- 1632048 TI - [Intranasal surgery (selected chapters)]. PMID- 1632049 TI - [Electromyography of the external muscles of the larynx in the combined diagnosis of hypokinetic dysphonia]. AB - Bioelectric activity of elevators and depressor of the thyroid cartilage were studied in 135 patients with hypokinetic dysphonia versus 30 healthy subjects. At the primary diagnosis and in controls this activity for the inferior muscles exceeded that for the superior ones 1.2-1.4-fold. One year after the diagnosis the superior muscles were 1.2-1.6-fold more active, whereas in later terms both activities correlated or the increase was less than 1.2-fold. Basing on the studies, early clinical signs of functional dysphonias are suggested promoting more precise diagnosis and decision on the voice problem treatment. PMID- 1632050 TI - [The effect of low temperatures on biochemical indicators in the blood of calves]. AB - Twenty calves, heifers of the Holstein-Friesian breed and crossbreds with the Slovak Pied breed, were divided into two groups at the average age of 19 days. The trial group was kept outdoors in wooden hutches and the control group was housed in an insulated building. Blood was sampled at the age of 20, 33, 48 and 60 days at the outdoor temperatures of 3 degrees C, -2 degrees C, -5 degrees C and -8 degrees C. The calves kept in hutches where temperatures were always lower than in the insulated calf-house had the higher level of nonesterified fatty acids in all observations. The largest, highly significant difference was determined at the age of 60 days at the outdoor temperature of -8 degrees C (271 mumol/l vs. 224 mumol/l), and the significance of differences was also observed in the first and third blood samplings at the temperatures of 3 degrees C and -5 degrees C. The differences were highly significant in the first group between the first and fourth, and second and fourth samplings. In the calves kept in the insulated building the difference was significant between the first and fourth observation because the content of free fatty acids was also gradually increasing in this case (Tab. I). Glycaemia values were also higher in the calves kept in hutches (Tab. II). The most noticeable (significant) difference was determined at the age of 48 days at the outdoor temperature of -5 degrees C (4.3 mmol/l vs. 3.9 mmol/l). Significant differences within the group were recorded only in calves from the trial group kept in hutches. Insulin concentrations increased gradually with the older age of animals (Tab. II). At the age of 20 days the values were identical in fact in both groups and the highest concentrations were recorded at the age of 60 days. The differences between the groups were not significant, the largest difference was observed at the end of milk feeding period at the age of 60 days (19 microUI/l in calves from hutches and 15.6 microUI/l in calves from the insulated building). Triiodothyronine concentrations decreased from the starting values of 0.8 nmol/l and 0.76 nmol/l in both groups at the age of 33 days to the values of 0.61 and 0.62 nmol/l.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1632051 TI - [Immunostimulatory effects of certain substances in experimental ascaridiasis in pigs]. AB - The effects were studied of four immunomodulative substances of biological origin (purified glucan, glucan with porcine immunoglobulin and zinc, transfer factor and vitamin A) on T and B lymphocytes, along with their protective effects in pigs with experimental ascariasis. These substances activated T and B lymphocytes with different intensity. The nonspecific stimulation of these cells in the blood of pigs with the immunomodulative substances intensified the protective mechanisms; this resulted in a decreased number of migrating ascaris larvae in the lungs of pigs by 17% to 65%. Of the four immunomodulative substances studied, transfer factor and glucan-based substances with porcine immunoglobulin and zinc proved to be the most effective. Both the substances exerted a significant stimulative effect on T- and B-cell populations even in the first days after infection, reaching the maximum on days 7-9 p. i. (Figs. 1 and 2). The protective effect, assessed by the reduction of migrating ascaris larvae in the lungs of pigs, was 62% and 65% using transfer factor and glucan preparation with homologous immunoglobulin and zinc, respectively. The percentage of occurrence of T and B lymphocytes, obtained by the use of purified glucan and vitamin A, was not in correlation with their protective effect (purified glucan 17%, vitamin A 50%). The immunomodulative effects of little effective purified glucan increased when combined with porcine immunoglobulin and zinc. The results are significant from the aspect of the nonspecific stimulation of immunity in ascariasis and in some other helminthoses. PMID- 1632052 TI - [Biochemical and histological changes in the hypothalamus in hormone-stimulated sheep]. AB - The effects were investigated of a hormonal preparation of serum gonadotrophin (SC) on neurosecretion, PAS-positive mucopolysaccharides and on histological changes in the third cerebral ventricle; at the same time variations were determined of catecholamine concentrations of ependyma surface in the hypothalamic regions that control directly reproductive functions in ewes of the Merino and Wallachian breeds in the oestrus period. Ewe oestrus was synchronized by insertion of Ageline (Spofa) sponges into the vagina. A dose of 2000 IU of serum gonadotrophin (Bioveta, Ivanovice in Hana) was administered to stimulate the ewes (n = 30). Twelve ewes of the Wallachian breed, six control and six test ones, were used for radioenzymatic detection of catecholamines (Catechola test, Prague). The brains were segmented immediately after bleeding and samples were taken from the eminentia medialis, area preoptica and corpus mamillare pursuant to the stereotactic configuration of the sheep hypothalamus (Welento et al., 1968). The brains of ten ewes of the Merino breed, four control and six test ones, and of eight ewes of the Wallachian breed (four control and four test ones) were used for histological treatment. For the purposes of a histological study, the brains were treated with current histological methods. The amount of neurosecretory material was assessed by light microscopy (Nakahara, 1963). Samples for the study of ependyma of the lower part of the third cerebral ventricle were examined in a scanning electron microscope. The obtained results demonstrate a statistically significant decrease by 36.4% (P less than 0.05) in epinephrin concentrations in the area preoptica of hypothalamus after SG administration (Fig. 3), in comparison with the control group. A decrease in norepinephrin concentration in the corpus mamillare (Fig. 4) was statistically significant (P less than 0.001). The dose of 2000 IU SG influenced most markedly catecholamine concentrations in the eminentia medialis (Fig. 5), where a statistically significant decrease in epinephrin and norepinephrin concentration was observed (P less than 0.01). Dopamine concentrations also decreased significantly (P less than 0.05) in the eminentia medialis (Fig. 5). Following the hormonal stimulation, a significant increase in dopamine and epinephrin concentrations was observed in the hypophysis of sheep (Fig. 6; P less than 0.05) and in the epiphysis there was a significant decrease in epinephrin and dopamine concentration (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1632053 TI - [Listeria monocytogenes in food]. AB - As in recent years laboratory diagnostics of listeria has become part of food microbiology, the frequency of occurrence of the bacteria Listeria monocytogenes has been followed in various kinds of foods for a year. A total of 51 strains of L. monocytogenes (7.2%) was isolated from 700 kinds of samples (raw milk, pasteurized milk, meat surface, poultry, cheeses, thermally not treated meat products, food--industry machinery). As can be seen in Tab. I, the highest number of strains was isolated from meat surfaces (13.5%), followed by meat--industry machinery (12.72%), poultry (10%) and cheeses (5%). The lower numbers of strains were found out in thermally not treated meat products (3.8%) and in raw milk (3.3%). Pasteurized milk did not contain any strains. Our findings in raw milk (3.3%) and in pasteurized milk (0) are in agreement with the data cited e. g. by authors from the USA (Lovett et al., 1987), who mention the value of 4.2% in raw milk and the zero value in pasteurized milk. The percentage of strains monitored in cheeses (5%) can be evaluated as low as the assortment of investigated cheeses was small (all strains were isolated from soft ripening cheeses). German authors (Tham et al., 1988) speak about the 2.5% percentage of L. monocytogenes strains; this is in keeping with our findings. The findings in thermally not treated meat products (3.8%) can be evaluated as low although the number of strains found in raw meat was high.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632054 TI - Hepatic storage of glycosaminoglycans in feline and canine models of mucopolysaccharidoses I, VI, and VII. AB - Livers from normal cats and dogs, cats with mucopolysaccharidoses (MPS) I and VI, and dogs with MPS VII were analyzed biochemically and morphometrically to determine the lysosomal storage of glycosaminoglycans (GAG) in these animal models of human genetic disease. Analyses were performed on liver samples from seven normal cats ranging in age from 13 weeks to 15 months; six MPS I-affected cats ranging in age from 10 weeks to 26 months; four MPS VI-affected cats ranging in age from 9 months to 32 months; four normal dogs ranging in age from 1 month to 47 months; and three MPS VII-affected dogs, 5 days, 11 days, and 14 months of age. All of the animals were from the breeding colony at the University of Pennsylvania School of Veterinary Medicine and were maintained in accordance with national standards for the care and use of laboratory animals. Each GAG subclass was quantitated, and total GAG concentration was determined. Liver from cats with MPS I had the highest total GAG concentration (5.7 times that of the control), followed by liver from dogs with MPS VII (1.8 times) and cats with MPS VI (1.5 times). These data were very closely correlated (R2 = 0.982) with the results of the morphometric analyses of hepatocyte and Kupffer cell vacuolation associated with lysosomal storage and support the validity of both methods. This is particularly important for the quantification of total and individual GAG concentrations in tissue preparations. The values obtained should prove useful in future assessments of therapeutic regimes, such as enzyme replacement, bone marrow transplantation, and gene therapy, for these genetic diseases. PMID- 1632055 TI - Uptake of ferritin by follicle-associated epithelium in the colon of calves. AB - Uptake of macromolecules (e.g., ferritin) by M cells in follicle-associated epithelium in small and large intestine was investigated in three healthy, conventionally raised, 2- to 3-week-old, female Holstein Frisian calves. A 2.5% solution of ferritin was injected into the ligated loops in mid-jejunum, in terminal ileum, in the ascending colon adjacent to the ileocecal junction, and in the proximal loop of the ascending colon containing gut-associated lymphoid tissue. After exposure times that ranged from 82 to 165 minutes, ferritin was detected in M cells of domes in the small intestine, as well as in cells in follicle-associated epithelium of proprial lymphoid nodules and lymphoglandular complexes of colon that morphologically resembled M cells of small intestine. Ferritin was found in apical invaginations, apical vesicles, multivesicular bodies, basal vesicles, and adjacent intercellular spaces. In addition to ferritin, apical vesicles, multivesicular bodies, and intercellular spaces contained 50-nm membrane-bound particles. More ferritin was endocytosed by M cells of the small intestine than by M cells of the large intestine. In the large intestine, higher amounts of ferritin were found in M cells of follicle associated epithelium overlying proprial lymphoid nodules than in M cells of follicle-associated epithelium in the depth of lymphoglandular complexes. Based on these results, we concluded that M cells of follicle-associated epithelium in the colon of calves provide a route for antigen uptake into the intestinal lymphoid system. PMID- 1632056 TI - Histopathologic and ultrastructural myocardial alterations in calves deficient in vitamin E and selenium and fed polyunsaturated fatty acids. AB - We developed an experimental model of nutritional degenerative myopathy in ruminant cattle. Fourteen experimental calves were fed a diet low in vitamin E and selenium for 127 to 137 days. Six of these calves were then euthanatized. After 127 days, a dietary additive of linseed oil that had been treated to protect it against ruminal hydrogenation was added to the low vitamin E and selenium diet of the eight remaining calves as a source of polyunsaturated fatty acids. Six of these animals were euthanatized after 6 to 11 days of polyunsaturated fatty acid feeding; the other two died after 6 and 8 days. Macroscopic myocardial alterations were seen in five polyunsaturated fatty acid fed calves but not in any other experimental calf. Microscopic lesions, comprising multifocal or diffuse cardiocyte degeneration and necrosis, were seen in atrial and ventricular myocardium of all experimental calves. These changes were more severe in polyunsaturated fatty acid-fed calves than in animals that did not receive polyunsaturates. Ultrastructurally, sublethally damaged cardiocytes had lysed contractile material; vacuolated sarcoplasm; altered mitochondria, sarcoplasmic myelin figures, and lipofuscin granules; and multiple nuclei. Necrotic cardiocytes had contracted myofibrils, pyknotic nuclei, mineralized mitochondria, and plasmalemmal disruption; the external lamina remained largely intact. Necrosis was followed by macrophage invasion and phagocytosis of necrotic debris. Repair of the lesions was by deposition of collagen and elastin fibers. No alterations were seen in the hearts of control calves fed vitamin E and selenium-supplemented diet. The induced myocardial lesions are similar to those of spontaneous nutritional degenerative myopathy in ruminant cattle. PMID- 1632057 TI - Neuropathologic findings of bromethalin toxicosis in the cat. AB - Ten random source male domestic shorthair cats, 2 to 6 years old and 3.0-4.4 kg body weight, were each given a single oral dose (1.5 mg/kg) of bromethalin (cat Nos. 1-5) or bait vehicle carrier (cat Nos. 6-10). Bromethalin-dosed cats developed a toxic syndrome characterized by ataxia, focal motor seizures, vocalization, decerebrate posture, decreased conscious proprioception, recumbency, depression, and semicoma. Bromethalin-dosed cats were euthanatized if seizure activity or hindlimb paralysis developed. Survival times were 48 hours (cat No. 1), 89 hours (cat No. 2), 90 hours (cat No. 3), and 97 hours (cat No. 4). Control cats (cat Nos. 6-10) and one bromethalin-dosed cat (cat No. 5) were euthanatized on day 20 after dosing. Spongy change (edema--characterized by the formation of vacuoles in extracellular spaces and myelin lamellae), hypertrophied fibrous astrocytes, and hypertrophied oligodendrocytes were observed in the white matter of the cerebrum, cerebellum, brain stem, spinal cord, and optic nerve of all bromethalin-dosed cats. Spongy change occasionally extended into contiguous cerebellar Purkinje cell layer and cerebral cortical gray matter. The severity of lesions varied among cats but was most pronounced in cat No. 5 (480 hours after dosing). A leukocytic inflammatory response, gitter cell (macrophage) response, or axonal degeneration was not observed in the vacuolated areas. Ultrastructural findings included separation of myelin lamellae at the interperiod lines with the formation of intramyelinic vacuoles (intramyelinic edema), rupture and coalescence of intramyelinic vacuoles into larger extracellular spaces (spongy change), and pronounced cytosolic edema of astrocytes and oligodendroglial cells. PMID- 1632058 TI - Toxic peripheral neuropathy with demyelination in Sprague-Dawley rats given CGS 21595--a 5-lipoxygenase inhibitor. AB - Male and female Sprague-Dawley rats were given CGS 21595, a pro-drug that is almost immediately metabolized to CGS 19213, a naphthoquinone that acts as a 5 lipoxygenase inhibitor. The compound was administered by gavage to five groups of Sprague-Dawley rats (group Nos. 1, 5, n = 30; group Nos. 2-4, n = 20) at daily doses of 0, 50, 150, 500, or 1,000 mg/kg for 13 weeks. Rats in the higher dose groups had a reduced weight gain, but significant neurologic signs were not observed. A peripheral neuropathy consisting predominantly of myelin destruction in the spinal nerve roots and sciatic nerves in male rats treated with greater than or equal to 150 mg/kg CGS 21595 and in female rats treated with greater than or equal to 50 mg/kg CGS 21595 for 13 weeks. This lesion was not fully reversible after a recovery period of 4 weeks. Lesions consisted of ballooning of myelin sheaths, infiltration by macrophages, demyelination, and occasional areas of remyelination. Axons were generally preserved, and the brain and spinal cord were not affected. Male and female rats in all treatment groups had cytoplasmic hyaline droplets in the proximal renal tubules. This change was reversible after 4 weeks and was not associated with any other adverse effects on the kidney. PMID- 1632059 TI - Langerhans' cells in equine cutaneous papillomas and normal skin. AB - Langerhans' cells (LC) were investigated immunohistochemically and electron microscopically in normal equine epidermis and 133 equine cutaneous papillomas experimentally induced in five 2-year-old Thoroughbred horses. Class II major histocompatibility complex antigen-positive dendritic LC were found in the normal epidermis and ultrastructurally had the characteristic Birbeck's granules. In the developing phase of the papillomas, LC were significantly decreased in number and size, indicative of a hypofunctional state. In the regressing phase of the papillomas, LC were markedly increased in number, especially at the epidermis dermis junction. LC with long dendrites were rich in cytoplasm with well developed cytoplasmic organelles, including Golgi apparatus, lysosomes, Birbeck's granules, and multivesicular bodies. These LC were hyperfunctional. An infiltration of many T lymphocytes was also observed at the epidermis-dermis junction. PMID- 1632060 TI - An atypical neuroendocrine tumor in the lung of a beagle dog. PMID- 1632061 TI - Ultrastructure of a spindle cell carcinoma in the mammary gland of a dog. PMID- 1632062 TI - Bovine focal proliferative fibrogranulomatous panniculitis (Lechiguana) associated with Pasteurella granulomatis. AB - In southern Brazil, cattle are affected by a disease known locally as Lechiguana and characterized by large subcutaneous swellings. Eighteen cases were examined clinically; 17 of the cattle had a single swelling, and one had two swellings. In 14 of the 18 cases, the swellings were located over the scapula and adjacent regions. The subcutaneous masses reached maximum dimensions of 45 x 50 cm, with heights above the skin surface of 5-25 cm. Growth was rapid, often taking place in 15 to 60 days. Histologically, all lesions were focal proliferative fibrogranulomatous panniculitis and consisted of focal proliferation of fibrous tissue that was infiltrated by plasma cells, eosinophils, lymphocytes, and sometimes neutrophils. An eosinophilic lymphangitis was also present, which sometimes resulted in the destruction of the lymphatics and the formation of eosinophilic microabscesses. Small granulomas, sometimes containing radiating clubs, and Splendore-Hoeppli material were present in the regional lymph node. Pasteurella granulomatis was isolated from the subcutaneous masses of 14 of the 18 natural cases. All 11 of these cases recovered following treatment with 3 g of chloramphenicol daily for 5 days. Untreated animals died. Because the area of anatomic distribution is similar to that infested by Dermatobia hominis, we postulate that this insect may transmit the causative agent. In one steer, a subcutaneous injection of P. granulomatis caused a large subcutaneous swelling consisting of interlacing bundles of collagen infiltrated by neutrophils, eosinophils, and some lymphocytes. Microabscesses, but not lymphangitis and granulomas, were detected. In all 11 cattle inoculated either intramuscularly or subcutaneously with P. granulomatis, purulent abscesses were produced at the sites of the injection, and P. granulomatis was recovered from all lesions. PMID- 1632063 TI - A qualitative assay for beta cell antibodies. Preliminary results in dogs with diabetes mellitus. AB - Purified beta cells from a radiation-induced transplantable rat insulinoma were used to detect beta cell antibodies in serum from untreated diabetic dogs. Serum from dogs in which anti-beta cell antibodies were induced by injecting a purified beta cell suspension subcutaneously was used as positive control. Following incubation with test sera, fluorescein-labeled anti-dog immunoglobulins were used to visualize binding between the beta cells and dog gamma globulins. Nine of the 23 diabetic dogs showed a strongly positive reaction which was characterized by a ring fluorescence, three showed a weak reaction and 11 were negative, i.e. they showed diffuse fluorescence. In contrast, 14 of the 15 healthy dogs showed diffuse fluorescence and one dog showed a weakly positive reaction. Thyroid, liver and kidney cells did not elicit ring fluorescence. Although females (spayed and intact) represented the majority of the diabetic dogs, there was no correlation between sex and the occurrence of antibodies in the diabetic dogs. There was also no correlation to the age of the dogs. In conclusion, we have developed a specific test for anti-beta cell antibodies. The test is reproducible and economical to perform on a large number of samples. PMID- 1632064 TI - Suppression of Ia antigen expression on gamma interferon treated macrophages infected with Ehrlichia risticii. AB - Ehrlichia risticii is an obligate intracellular bacterium of monocytes/macrophages. In this report, using immunofluorescence staining, flow cytometry, and Kolmogorov-Smirnov analysis of histograms, the response of P338D1 and peritoneal macrophages stimulated with recombinant murine interferon-gamma (rIFN-gamma) was examined for the expression of major histocompatibility complex Class II gene product (Ia) and effect of E. risticii infection on induction of Ia surface expression. Maximal expression of Ia by sham-infected P388D1 cells was observed 2 days post rIFN-gamma addition followed by a progressive decline. These stimulatory effects of rIFN-gamma were dose dependent. Relative to sham-infected P388D1 cells, the induction of Ia by rIFN-gamma (200 U ml-1) on E. risticii infected P388D1 cells was significantly suppressed at each time point tested through Day 5 with maximal suppression of 88% occurring on Day 2. Similarly, the induction of Ia by rIFN-gamma on E. risticii-infected peritoneal macrophages was significantly suppressed by 77% (fluorescent microscopy) when compared to sham infected peritoneal macrophages. The higher dose of rIFN-gamma (2000 U ml-1) failed to restore Ia surface expression by E. risticii-infected P388D1 cells. The suppression of Ia on P388D1 cells in response to RIFN-gamma was not related to the degree of infection of these cells by E. risticii. A soluble inhibitor substance was not demonstrable in the supernatant from E. risticii-infected cells, nor were inhibitor levels of prostaglandin E2 levels found in the supernatant. Suppression of surface Ia expression on the macrophage suggests a mechanism whereby I. risticii may evade T-lymphocyte recognition, hinder antigen specific T-lymphocyte activation, and promote their own survival. PMID- 1632065 TI - Swine leukocyte antigen and macrophage marker expression on both African swine fever virus-infected and non-infected primary porcine macrophage cultures. AB - Swine leukocyte antigens (SLA) and a macrophage specific marker were monitored on porcine macrophages cultured with or without macrophage colony stimulatory factor (M-CSF) and on cells infected with African swine fever virus (ASFV). SLA expression was maximal either in the total cell extract or on the cell surface at 3-4 days of culture; after 4 days these values began to decrease. Fluorescence analyses of immunostained macrophages cultured with or without M-CSF indicated a major upward shift in the number of SLA Class I molecules on individual macrophages whereas for SLA Class II both a novel expression of Class II and an upward shift in the number of molecules per cell were evident. Infection of 3-day old macrophage cultures with three different isolates of ASFV resulted in minor changes in surface expression of SLA Class I, SLA Class II, and macrophage markers. No differences in infection with ASFV was observed whether macrophages were SLA Class II positive or negative, nor was there blocking by anti-SLA Class I or Class II monoclonal antibodies of ASFV infection of cultured macrophages. PMID- 1632066 TI - Generation and functional characterization of ovine bone marrow-derived macrophages. AB - A method for the culturing and propagation of ovine bone marrow-derived macrophages (BMM) in vitro is described. Bone marrow cells from sterna of freshly slaughtered sheep were cultured in hydrophobic (teflon foil) bags in the presence of high serum concentrations (20% autologous serum and 20% fetal calf serum). During an 18 day culture period in the absence of added conditioned medium, and without medium change, a strong enrichment of mononuclear phagocytes was achieved. Whereas the number of macrophages increased four to fivefold during this time, granulocytes, lymphoid cells, stem cells and undifferentiated progenitor cells were reduced to less than 3% of their numbers at Day 0. This resulted in BMM populations of 94 +/- 3% purity. These cells had morphological and histochemical characteristics of differentiated macrophages, and they performed functions similar to those of non-activated, unprimed human monocyte derived macrophages. Thus, they avidly ingested erythrocytes coated with IgG of heterologous or homologous origin. They expressed a modest level of procoagulant activity, but upon triggering with lipopolysaccharide (LPS), a marked increase in cell-associated procoagulant activity was observed. LPS triggering promoted the secretion of interleukin-1, as evidenced by measurement of murine thymocyte costimulatory activity, and transforming growth factor-beta. Using the mouse L929 cell cytotoxicity assay as an indication of tumor necrosis factor (TNF) activity, no TNF activity was detected in the same supernatants, a result possibly due to species restriction. BMM generated low levels of O2- upon triggering with phorbol 12-myristate 13-acetate (PMA). On the other hand, no O2- production was observed upon stimulation with zymosan opsonized with ovine or human serum. Using luminol enhanced chemiluminescence (CL) as a more sensitive indicator of an oxidative burst, both PMA or zymosan were able to trigger CL, but the response was subject to partial inhibition by sodium azide, an inhibitor of myeloperoxidase. This points to non-macrophage cells contributing also to the CL response, and is consistent with the view that unprimed BMM elicit a low oxidative burst upon triggering with strong inducers of a burst. Our functional characterization now allows us to apply priming and activation protocols and to relate their effect to functional alterations. PMID- 1632067 TI - A lactogenic-immune-deficiency-syndrome in cows: unexplained phenomenon. AB - The majority of adult cows in a certain dairy herd, were found to have very low levels of immunoglobulins (Igs) in their colostrum. This phenomenon was defined by us as Lactogenic-Immune-Deficiency-Syndrome (LIDS). The mean IgG levels were 44.5 and 57.2 mg ml-1 respectively (on two different occasions) as compared to that of a control group which was 103.4 mg ml-1. The levels of Igs in the colostra of heifers from the same herd were found to be higher than those of adult cows. The degree of LIDS was found to be closely related to the age of cows in the herd. The low levels of Igs in the colostra were not directly linked to their concentrations in the sera of the affected cows. The relatively low amount of IgA in the affected colostra suggests that the local production in the lymph tissue associated with the mammary glands is impaired as well. In order to investigate the etiology of the phenomenon, tests were carried out to reveal whether bovine leucosis virus (BLV) infection or immune complexes were involved in the pathogenesis of LIDS. The results were negative. The etiology of LIDS remains for the time being unknown. PMID- 1632068 TI - Changes in cell-mediated immune responses after experimentally-induced anaphylaxis in dogs. AB - Experimentally-induced type 1 hypersensitivities were induced in normal dogs to either ovalbumin or Ascaris antigen. In vitro and in vivo cell-mediated immune responses were measured before sensitization and again at 1 and 6 days after induction of anaphylaxis by intravenous challenge with antigen. Histamine modulated lymphocyte functions, such as histamine-induced suppression, histamine co-mitogen induced blastogenesis and the in vivo cutaneous responses to intradermally injected mitogens decreased post anaphylaxis. Spontaneous suppression of the autologous mixed-lymphocyte reaction increased post anaphylaxis. Lymphocyte blastogenic response to Concanavalin A (Con A) decreased at 6 (but not at 1) days post anaphylaxis probably due to a mediator other than histamine. Blastogenesis of 24 h preincubated cells by suboptimal concentration of Con A, declined post anaphylaxis, but Con A-induced suppression was not significantly altered. Dogs with atopic dermatitis have some altered cell mediated immune responses. Altered histamine-induced and spontaneous suppression, histamine suppression of mitogenesis and decreased contact sensitivity observed in this experimental type 1 hypersensitivity mimicked that of atopic dogs. Increased cutaneous response to mitogens observed in atopic dogs was not reproduced in the type 1 hypersensitive dogs. These findings suggest some of the altered cell-mediated immune functions observed in dogs with atopic dermatitis result from type 1 hypersensitivity. The other abnormalities may be intrinsic to the atopic state. PMID- 1632069 TI - An assay to quantitate the binding of Rhodococcus equi to macrophages. AB - A Rhodococcus equi radiobinding assay has been developed using organisms labeled with 3H-uracil. These labeled organisms resemble their unlabeled counterparts with respect to colony morphology, viability, and buoyant density. Bacteria routinely incorporate between 5 x 10(-3) and 5 x 10(-2) counts per minute per colony forming unit (cfu) which in this assay allows the detection of fewer than 0.2 cfu per macrophage. Once incorporated, greater than 90% of the label remains bacterial associated for at least 4 h postlabeling. The majority of the label is trichloroacetic acid precipitable, partitions into the aqueous phase following phenol/chloroform extraction and is ethanol precipitable. RNAse treatment of the ethanol precipitate abolishes label trichloroacetic acid precipitation. This radiolabeling technique has been used to quantitate the attachment of R. equi to both murine peritoneal and equine alveolar macrophages adherent to 13 mm glass coverslips. R. equi binding is dose dependent, saturable, and specific to macrophages. Further, binding is enhanced in the presence of fresh serum. Inhibition of radiolabeled bacterial binding can be obtained by competition with cold R. equi. This radiolabeled binding assay represents a crucial step in identifying the receptors on macrophages involved in the recognition of R. equi and may help to provide information on how macrophages recognize intracellular bacteria in general. PMID- 1632070 TI - Proliferative response of mammary gland mononuclear cells to recombinant bovine interleukin-2. AB - Methods of augmenting bovine mononuclear cell responsiveness during physiological transitions of the udder may enhance resistance of the mammary gland to intramammary infections. Interleukin-2 is required for proliferation of T lymphocytes and may contribute to B-lymphocyte proliferation. Recombinant bovine interleukin-2 (rBoIL-2) was evaluated as a potential immunoenhancer of bovine mammary gland mononuclear cells. Bovine mononuclear cells were isolated from five primiparous Holstein cows at 14-18 and 28-32 days of involution and at 7-13 days prior to parturition. Bovine blood and mammary gland mononuclear cells were highly responsive to rBoIL-2. Response of mammary gland mononuclear cells to rBoIL-2 was comparable with response of blood mononuclear cells. These data suggest that rBoIL-2 may be an effective immunoenhancer of bovine mononuclear cells during the non-lactating and prepartum periods. PMID- 1632071 TI - Determination of optimal in vitro conditions for caprine alternative complement pathway assay. AB - Optimal in vitro testing conditions for caprine alternative complement pathway assay were determined. Effects of the following variables were tested: heterologous erythrocytes; pH, ionic strength and Mg2+ ion concentration of the complement diluent; incubation time and temperature. Rabbit erythrocytes were the optimal target cells. The optimal buffer conditions were: pH 8.0, ionic strength 0.06 mmol NaCl and 5mmol Mg2+ ion. Optimal incubation time and temperature were 75 min and 30 degrees C, respectively. PMID- 1632072 TI - Immunophysiological studies of interleukin-2 and canine lymphocytes. AB - Interleukin-2-dependent pathways of lymphocyte activation were investigated in canine peripheral blood lymphocytes (PBL) following stimulation with T-cell mitogens including phytohemagglutinin, phorbol ester (TPA), calcium ionophore (ionomycin), and human recombinant interleukin-2 (hrIL-2). The ability of the stimulated cells to produce interleukin-2 (IL-2) was determined using murine indicator cell lines. IL-2 receptor expression by mitogen-stimulated canine PBL was confirmed by the binding of hrIL-2 with high affinity, and with characteristics comparable to those of the human and murine IL-2 receptor. Examination of serum and PBL from two dogs that were treated with hrIL-2 and human recombinant tumor necrosis factor for systemic mast cell tumors showed that in one dog, IL-2 could be measured in the serum. Concurrently, the in vitro mitogenic response of this dog's PBL to hrIL-2 occurred earlier, possibly reflecting an increase in the relative number of IL-2-responsive cells within the PBL population. PMID- 1632073 TI - Effects of route of immunization, adjuvant and unrelated antigens on the humoral immune response in lines of chickens selected for antibody production against sheep erythrocytes. AB - Effects of intramuscular (i.m.), intravenous (i.v.) and intraperitoneal (i.p.) primary immunization with the T-dependent antigen, sheep red blood cells (SRBC), was studied in two chicken lines selected for either high (H) or low (L) antibody response after i.m. immunization with SRBC. The primary route of immunization affected the line differences in the primary response and in the secondary response after i.m. reimmunization. Intravenous immunization with the T-dependent antigen bovine serum albumin (BSA) showed line differences similar to those found after i.m. or i.v. immunization with SRBC. Immunization with both the partially T independent antigens Brucella abortus (BA) or Salmonella H-antigen (SHA) revealed no line effect. Immunization with SRBC in incomplete Freund's adjuvant (IFA) did not change the difference between lines, whereas immunization with complete Freund's adjuvant (CFA) diminished the difference between lines. It is postulated that differences in antibody production between the selected lines might be attributed to differences in T-cell activity. PMID- 1632074 TI - The production of equine monoclonal immunoglobulins by horse-mouse heterohybridomas. AB - Studies were carried out to determine the optimum conditions for the production of equine monoclonal antibodies (MAbs). Lymphocytes from ponies immunised with influenza A equine 2 virus, isolate A/Equine/Newmarket/79 (H3N8) were fused with mouse myeloma (NSO) cells and with horse-mouse heterohybridomas made aminopterin sensitive by selective growth in 8-azaguanine. Although all fusions initially resulted in heterohybridoma colonies that secreted equine immunoglobulin, many of these were unable to maintain secretion for longer than a few weeks. Increasing the time between immunisation and the booster injection of Newmarket/79 virus, the inclusion of Freund's incomplete adjuvant and the use of an aminopterin sensitive primary heterohybridoma as the fusion partner, improved the production of HIg-secreting heterohybridomas. After two clonings eight cell lines were established which maintained anti-Newmarket/79 antibody secretion for over a year. FACS analysis of the cell lines provided a useful means of predicting breakdown of MAb secretion by the cell lines, thus enabling re-cloning to be carried out in time. PMID- 1632075 TI - An enzyme-linked immunosorbent assay (ELISA) for von Willebrand factor antigen (vWf-Ag) in canine plasma. AB - A quantitative enzyme-linked immunosorbent assay (ELISA) has been developed to measure canine von Willebrand factor antigen (vWf-Ag) in plasma of the dog. A vWf Ag antiserum was raised in rabbits and purified by preabsorption with the low molecular weight vWf-Ag-deficient fraction of canine cryoprecipitate, followed by affinity chromatography on protein-A Sepharose. The rabbit anticanine vWf-Ag IgG was used to bind the vWf-Ag of the test plasmas to the solid phase and to prepare the enzyme-antibody conjugate in ELISA. Normal rat serum was used as blocking agent. The standard curve was linear (r2 greater than 0.98) and reproducible after logit-log transformation. The interassay coefficient of variation (CV) in test plasmas with various vWf-Ag concentrations was never greater than 7.7%. Assayed values in dilutions of pooled normal canine plasma added to canine vWf-Ag deficient plasma were linear between 0 and 100% (r2 = 0.99) and indicated excellent analytical recovery of vWf-Ag. In 18 dogs with various internal diseases, including von Willebrand's disease and haemophilia A, the coefficient of correlation between the results of the ELISA and those of electroimmunodiffusion (EID) was 0.93. PMID- 1632076 TI - Use of rats to compare atrophic rhinitis vaccines for protection against effects of heat-labile protein toxin produced by Pasteurella multocida serogroup D. AB - Four bacterin-toxoid and three bacterin commercial vaccines against atrophic rhinitis were tested in rats for their capacity to immunize against the lethal and systemic effects of purified heat-labile protein toxin (D-toxin) produced by Pasteurella multocida serogroup D. Only one bacterin-toxoid vaccine stimulated sufficient immunity to prevent the death of all rats challenged with D-toxin. None of the vaccines prevented weight loss, leukocytosis or increases in serum complement titers in rats challenged with D-toxin. Rats provide an inexpensive animal model for testing the capacity of vaccines to generate antitoxic immunity against the lethal and systemic effects of D-toxin. PMID- 1632077 TI - Anti-lymphocyte antibodies generated in animals immunised with Theileria annulata infected cells. AB - Complement fixing antibodies were measured in sera from animals immunised with either Theileria annulata sporozoites or autologous or allogeneic schizont infected mononuclear cells using a complement-mediated micro-cytotoxicity test. The test demonstrated the presence of anti-lymphocyte antibodies in allogeneic cell-immunised animals, which were not detectable in autologous cell- or sporozoite-immunised animals; also that these antibodies were directed to T. annulata-infected and (MHC) class I antigens. Their potential importance in repeated immunisations is discussed. PMID- 1632079 TI - Kinetics of ovine interferon-gamma production: detection of mRNA and characterisation of biological activity. AB - The kinetics of interferon-gamma (IFN-gamma) production were studied in sheep mesenteric lymph node (MLN) cells at the molecular level using an ovine IFN-gamma cDNA probe and by bioassay which was verified by blocking antiviral activity with a monoclonal antibody (Mab) against recombinant bovine IFN-gamma IFN-gamma mRNA appeared in MLN cells within 4 h of stimulation with phorbol ester and Concanavalin A and was not detectable by 72 h after stimulation. Biologically active IFN-gamma appeared in the culture supernatants 8 h after stimulation and was still present 96 h later when de novo synthesis had terminated. Acid dialysis and Mab neutralisation demonstrated conclusively that native ovine IFN-gamma is a pH 2 labile cytokine. PMID- 1632078 TI - Detection of canine interleukin-2 receptors by flow cytometry. AB - This study describes a method for detecting canine interleukin-2 receptors (IL 2R) by flow cytometry, using human recombinant IL-2 labeled with phycoerythrin (IL-2-PE). Peripheral blood mononuclear cells from four normal dogs were washed, incubated with IL-2-PE, and then washed to remove any unbound IL-2-PE. Flow cytometric analysis of the cells was performed with a 488 nm argon laser while gating on lymphocytes. Cells expressing the IL-2R were identified by their fluorescence as compared to cells stained with an anti-mouse immunoglobulin-G conjugated to phycoerythrin. The average percentage of resting cells expressing the IL-2R was found to be 21%. The addition of unlabeled human recombinant IL-2 to Day 3 phytohemagglutinin (PHA)-stimulated cells reduced the fluorescence intensity four-fold, thereby demonstrating the specificity of IL-2-PE for canine IL-2R. Following stimulation with optimal concentrations of PHA, the percentage of cells expressing the IL-2R increased daily and reached a maximum on Day 3 (76.4%). IL-2R density, as measured by mean fluorescence intensity, also increased and reached maximal levels on Days 2-3 (twenty-fold greater than resting cells). The binding, inhibition, and kinetic experiments provide evidence that human recombinant IL-2-PE is a useful tool for studying canine IL-2R expression. Thus, a one-step direct method for the flow cytometric detection and quantification of the canine IL-2R is now available. PMID- 1632080 TI - Biochemical analysis by SDS-PAGE and western blotting of the antigenic relationship between Leptospira and equine ocular tissues. AB - The antigenic relationship between Leptospira interrogans, equine cornea and lens was previously noted in our studies. Serum antibodies from horses inoculated with serovars wolffi, pomona, icterohaemorrhagiae, and tarassovi, were able to bind to five antigenic fractions from both cornea and lens, as demonstrated by immunoblotting. These antigens seem to be made up of protein and carbohydrates. After treatment with periodate for cleavage of glycoside ring structures, those fractions kept their condition of target for anti-Leptospira antibodies. Nevertheless, all fractions lost that condition after being subjected to peptide hydrolysis. PMID- 1632081 TI - Effects of weaning on antibody responses in young calves. AB - Two experiments were performed to investigate the effects of cessation of feeding milk substitute (weaning) on antibody responses to Keyhole Limpet haemocyanin (KLH) in young calves. In the first experiment, 47 calves were weaned at 42 days of age, while a further 47 calves remained unweaned until 84 days of age. All calves were immunized with KLH at 43 and 85 days of age. Serum IgG1, IgG2 and IgA responses to KLH were increased in the early weaned calves compared with the late weaned calves following both primary and secondary immunizations. In the second experiment, 24 calves were immunized with KLH at 21 days of age. Subsequently, at 35 days of age, eight calves were weaned, eight calves were sham-weaned and eight calves remained unweaned. Sham-weaning involved continuing to feed milk substitute of greatly decreased nutritional value in an attempt to isolate nutritional from behavioural effects of weaning. No effects of treatments on antibody responses were detected. It was concluded that weaning affects antibody responses to antigens given near weaning but not to antigens given 2 weeks before weaning. PMID- 1632083 TI - Inventory of pain data from the National Center for Health Statistics. PMID- 1632082 TI - Evidence for conservation of peripheral lymphocyte homing receptors between the bovine, murine and human species. AB - In rodents and humans, lymphocytes circulate throughout the body and return preferentially to their tissues of origin via a process termed homing. The specificity of homing is controlled by the binding of tissue-specific receptors on lymphocytes to ligands on specialized high-walled endothelial venules (HEV) found in lymphoid tissue. The murine and human peripheral lymphocyte homing receptors (PLHR) have been characterized and shown to be similar to each other. We present evidence for a similar receptor in the bovine. Bovine peripheral blood lymphocytes (PBL) bind to the HEV of murine peripheral lymph node tissue in vitro. The same sugars that have been shown to decrease the binding of murine or human lymphocytes to murine HEV also decrease the binding of bovine PBL to murine HEV. Neuraminidase treatment affects lymphocyte binding in a similar manner in the bovine, murine and human species. Phorbol myristate acetate (PMA) stimulation, which has been shown to reduce the expression of murine and human PLHR, also reduces the binding of bovine PBL to murine HEV. These data suggest conservation of PLHR between these species. PMID- 1632084 TI - [The psychosomatic approach in clinical practice]. AB - The author summarizes demands essential for successful implementation of the psychosomatic, i.e. biopsychosocial approach in everyday clinical practice. With regard to the complete shortage of comprehensively conceived psychosomatic centres, the author considers it useful to replace extra-mural psychiatric and psychological services to a maximum extent by consultant ("liaison") psychiatrists and psychologists. Team cooperation of specialists, mostly with a biomedical orientation, with specialists from the psychosocial sphere is an asset for patients as well as for medical thinking. This collaboration gives specialists of both represented models some new demands, in particular the need to find a common language, to define competences and for both an extension of the view on the problems. It opens the possibility of more effective cooperation with the patient's family and moreover the psychiatrist and psychologist can try to reduce stressing influences and attempt their prevention which is also to the benefit of health professionals. PMID- 1632085 TI - [Genealogic study of hypertrophic cardiomyopathy in the Czech population]. AB - In order to test the type of heredity and to assess further genealogical characteristics in our population the authors examined 105 families with hypertrophic cardiomyopathy. The families were subjected to clinical, electrocardiographic and echocardiographic examination of relatives (72% grade 1 relatives) as well as to a genealogical and psychological examination. For the proband's siblings the empirical risk of disease was 24%, in male probands it wts four times higher for brothers than sisters, in female probands it was three times higher in sisters. The sex ratio of six siblings in men was 20:4, in women 3:14. For children the risk was substantially higher in youner probands (under 30 years risk 40%, above 51 years 6.7%). The proband's parents were affected in 28%, fathers almost twice as frequently in male probands, and equally frequently in female probands. Fitness (reproduction fitness, f) was substantially reduced in the entire group, in isolated and familial cases and in different age groups, more in women than in men. The gene penetrance (assuming monofactorial heredity) was estimated by the method of definite carriers as 50%. Earlier manifestations (anticipation) and a more severe course of the disease was observed practically in all families with occurrence of the disease in more than 2 generations (influence of selection--sampling error). In our group the heredity in hypertrophic cardiomyopathies was not simple autosomal dominance, it was not possible to rule out heterogeny, phenocopy, sexual influence. On the other hand, the group was too small to make possible unequivocal conclusions and the data were not quite consistent with data in the literature. Genetic counselling, possibly DNA diagnosis, would be needed to elucidate heredity of this disease. PMID- 1632086 TI - [Creatine kinase and lactate dehydrogenase in the early diagnosis of acute myocardial infarct]. AB - The authors investigated in a group of 504 patients--357 men and 147 women with acute myocardial infarction on admission to hospital--the relationship between the ECG finding and values of catalytic concentrations of isoenzymes CK-MB and LD 1 LD-2. They found that isoenzymes CK-MB and LD-1 LD-2 are a more sensitive indicator of acute IM than the ECG tracing. Not even a negative ECG tracing when the total catalytic concentrations of CK and LD are not elevated rules out the possibility of acute myocardial infarction. PMID- 1632087 TI - [Magnesium loading test in cardiovascular diseases]. AB - The author presents an account of results of the magnesium loading test and its method, from a group of 50 patients with cardiovascular diseases. The magnesium loading test reveals shortage of bodily reserves of magnesium (mg) by calculating the percentage of Mg retention. In a group of examined subjects the author found a high percentage of Mg retention (on average 68%) which suggests an unequivocal deficiency of bodily Mg reserves in this group of patients. At the same time changes of serum concentrations and urinary excretion of other investigated minerals are discussed. As compared with other methods of assessment of Mg bodily reserves, the loading test is most suitable for clinical practice. In the discussion the author analyzes the assembled results and factors which lead to deficiency of bodily Mg reserves and deals with substitution treatment by Mg preparations. PMID- 1632088 TI - [Drug therapy in vascular occlusions of the lower extremities]. AB - The authors report their three-year experience with application of thrombolytic treatment in 31 patients with vascular occlusions of the lower extremities. They were successful in two thirds of the patients. The authors analyze the advantages and shortcomings of systemic or selective administration of antithrombotic therapy. Concurrent administration of hyperbaric oxygen is a rational therapy. PMID- 1632089 TI - [Diabetic osteopathy. Favorable effect of treatment of osteomalacia with vitamin D and calcium on high blood glucose levels]. AB - A group of 61 diabetics (incl. 35 treated by diet alone and 26 who were treated also by oral antidiabetics) with associated osteomalacia were treated with vitamin D (dosage 42,000 to 85,000 i. u. per day) and calcium (470-700 mg/day). After six weeks of this treatment the serum calcium level rose on average by 0.15 mmol/l and the blood sugar level declined on average by 1.68 mmol/l. A linear negative correlation was proved between these two parameters. The fasting blood sugar level declined in 53 subjects (86.88%) and only in five patients (8.19%) the blood sugar level increased, in three subjects (4.91%) it did not change. Possible explanations of this phenomenon include the influence of an increased calcium concentration on insulin secretion and release from pancreatic beta-cells on the one hand and enhanced glucose utilization in the periphery on the other hand. PMID- 1632090 TI - [Plasma viscosity. The effect of plasma proteins]. AB - The authors assessed the plasma viscosity by means of a capillary viscosimeter of their own design and assessed at the same time the concentration of 22 plasma proteins or lipids. Based on the results of these examinations it proved possible to elaborate an original equation which describes the plasma viscosity as a function of the concentration of fibrinogen, alpha-2-globulins (and among them most probably haptoglobin), gammaglobulins, IgA and IgM. The authors discuss in detail the importance of this finding for clinical haemorheology. PMID- 1632091 TI - [Free oxygen radicals in patients with hyperlipoproteinemia]. AB - The authors investigated the effect of hyperlipoproteinaemia on the formation of free oxygen radicals to which a significant role in the genesis of atherosclerosis is ascribed. They cause among others peroxidation of blood lipids with formation of lipoperoxides with a higher atherogenity. Using the method of luminol-dependent chemiluminiscence, their spontaneous and activated production in phagocytic blood cells was examined in a group of patients investigated on a long-term basis on account of hyperlipoproteinaemia (n = 24). The results were compared with a group of healthy subjects (n = 20); concurrently also blood lipids were examined. The authors revealed a statistically significant reduction of the spontaneous production of free oxygen radicals in the group of patients with hyperlipoproteinaemia. On examination of the activated production the drop of oxygen radical formation was at the borderline of statistical significance. PMID- 1632092 TI - [Antibodies against gastric parietal cells and thyroglobulin in various diseases in humans]. AB - The authors examined antibodies against antigen of gastric parietal cells using the method of reaction of complement-binding and the immunofluorescence test in 662 patients. Concurrently they examined in 443 patients of this group also antibodies against thyroglobulin. The group comprised 312 men and 350 women. For statistical evaluation the chi 2 test was used. Antibodies against the antigen of parietal cells were positive at the level of significance p less than 0.05 in the group with other diseases, at the level of significance of p less than 0.01 in dyspeptic syndrome, and at the level of significance p less than 0.001 in hypothyroidism and in chronic hepatopathies. The immunofluorescence test was statistically significant at the level of p less than 0.01 only in duodenal ulceration, at the level of p less than 0.001 in dyspeptic syndrome, hypothyroidism, hyperthyroidism, chronic hepatopathies, chronic pancreatitis, cholecystopathies, nephropathies and in the group of other diseases. Thyroid antibodies were positive with titres of p less than 1: 50 in 5.63, with titres of p less than 1: 5000 in 3.03%. The mentioned disease have not only pathomorphological and aetiological similarities but there is also serological overlapping. PMID- 1632093 TI - [Asymptomatic cholecystolithiasis in an ultrasonography study from Trencin]. AB - The author examined 1952 girls and women aged 15 to 92 years by ultrasonography. The incidence of cholecystolithiasis in the group without complaints was 8.19% in the group with atypical complaints it was 17.67% and in the group with typical complaints it was 75.0%. The ratio of asymptomatic cholecystolithiasis of the first two groups combined was 67.0% of the total. The ratio of cholecystectomies in the total number of cases with cholecystolithiasis was 30.9%. The clinical manifestation of cholecystolithiasis is influenced greatly by genetic factors, i.e. symptomatic lithiasis in the mother. Prophylactic cholecystectomy in case of asymptomatic cholecystolithiasis should not be recommended. PMID- 1632094 TI - [Pulmonary embolism as a rare complication of a contusion in the inguinal region]. AB - In the submitted case-history the authors describe the clinical case of an adolescent patient who developed phlebothrombosis of the right ileofemoral area one year after a blunt injury in the scrotal and right inguinal area. The symptoms of pulmonary embolism were detected sooner than the symptoms of phlebothrombosis. Two-dimensional echocardiography provided valuable information when the authors monitored the dynamics of changes in acute cor pulmonale and the effect of administered treatment. PMID- 1632095 TI - [Quality control in hematology]. AB - Qualified quality control is a necessary part of modern haematology: we cannot deem laboratory results reliable until effective quality checking is included. Quality assessment includes external (national, regional) and internal (intra laboratory) control. We suggest to found a Czech national external quality control agency for haematology based on principles which were declared by the World Health Organization. Internal control includes correct identification of samples, analytical control (standardization of test, evaluation of accuracy and precision) and biological quality control (history of patient's characteristics, relation to other laboratory results in clinical context). The deviation index, which is expressed either as a number or verbally 'excellent', 'good', 'satisfactory', or 'unsatisfactory', can supply rapid information on the quality of results in the haematological laboratory. PMID- 1632096 TI - [Present views on the diagnosis of cavernous hemangioma of the liver using ultrasound]. AB - The submitted review deals with morphometry, normal sonographic anatomy and the position of ultrasonography in the diagnosis of cavernous haemangiomas of the liver. The authors draw attention to the contemporary equipment used and analyze the position of other diagnostic methods in the diagnosis of cavernous haemangiomas of the liver. They discuss also the problem of percutaneous biopsy of the liver when this benign tumour is suspected. Finally the authors recommend the best procedure in the diagnosis of cavernous haemangiomas of the liver. PMID- 1632097 TI - [Modern development of cardiac pacing]. AB - In the submitted review the author presents after a historical introduction the contemporary possibilities of permanent pacing. He mentions the main reasons why a fixed rate pacing without atrioventricular synchronization is unphysiological and led to the development of dual chamber DDD pacemakers and ventricular pacemakers with a variable frequency of pacing. The main contribution of this so called physiological pacing is an increase of the cardiac output and the work capacity of patients, as compared with fixed rate pacing. The author present also examples of diagnostic and antitachycardiac stimulation and discusses possibilities of their combination with an implantable cardioverter-defibrillator in ventricular tachyarrhythmias. PMID- 1632098 TI - Current dental chemotherapeutics. PMID- 1632099 TI - Prenatal diagnosis: can what counts be counted? PMID- 1632100 TI - Reducing distress associated with pelvic examinations: a stimulus control intervention. AB - The effect of a new pelvic examination gown on patients' experienced discomfort during pelvic examination was tested. It was hypothesized that a better designed gown would reduce reported distress. Subjects were 87 patients at a private gynecology clinic. Age ranged from 17 to 72. Informed consent was obtained and patients were randomly assigned to either the experimental gown or the standard drape condition. Following examination, subjects completed questionnaires assessing demographic characteristics, state and trait anxiety, desired changes in pelvic examination procedures, and reactions to the examination. The attending nurse recorded heart rate and blood pressure. Results supported the hypotheses. Experimental subjects rated the gown as more comfortable than control subjects rated the drape. Experimental subjects desired fewer changes in exam procedures than control subjects, indicating that the gown provided them with an overall more comfortable experience. PMID- 1632101 TI - Depression and maladaptive eating practices in college students. AB - University students (n = 234) enrolled in sections of a required undergraduate course were administered the Center for Epidemiologic Studies Depression (CES-D) Scale and the Maladaptive Eating Behavior (MEB) Scale to determine if selected maladaptive eating practices correlated with depressive symptoms. Stepwise multiple regression on data from female subjects (n = 138) revealed that four eating practices related to depression, and produced a multiple R = .68, accounting for 46.2% of the variance. Maladaptive eating practices were not predictive of depression among males (n = 96) with "feeling uncomfortable eating in the presence of others" the only significantly correlated variable. This study confirms previous research that has found an association between maladaptive eating practices and depressed mood in nonclinical samples of university students. PMID- 1632102 TI - Was it murder or insanity? Reactions to a successful paroxysmal insanity plea in 1865. AB - This 1865 Harris/Burroughs trial marked the first time that the paroxysmal [temporary] insanity plea was supported by expert medical testimony in a U.S. courtroom. Jurors agreed that the female defendant was insane at the time of the shooting due to being "crossed in love and suffering from painful dysmenorrhea." Attitudinal stances of the legal system, health professionals, newspapers and the public are illustrated. By merely changing the antebellum language, the reactions could be recycled into our current tabloid newspapers and titillating TV programs as if the tragedy occurred yesterday. PMID- 1632103 TI - Worker and mother roles, spillover effects, and psychological distress. AB - This paper examines the relationship between the occupancy and quality of multiple-roles and psychological distress in a stratified random sample of 403 women employed as licensed practical nurses and social workers. We examined the main effects of the quality of the employee and parent roles and the interaction effects between these variables. Negative- and positive-spillover effects, from job to parenting and from parenting to job, were examined in an attempt to illuminate the processes by which multiple roles affect employed mothers' vulnerability or resilience to psychological distress. We found no negative spillover effects from job to parenting or from parenting to job, but we did find positive-spillover effects from job to parenting. Women with rewarding jobs were protected from the negative mental-health effects of troubled relationships with their children. This protection accrued to employed mothers regardless of their partnership status or the age of their children. Although based on cross sectional analyses, these findings suggest mechanisms by which employed mothers reap a mental-health advantage from multiple roles, even when some of those roles are stressful. PMID- 1632104 TI - Study on the metabolism of racemic prolintane and its optically pure enantiomers. AB - 1. Asian and European volunteers were given racemic prolintane, and the metabolites in the 24 h urine were identified and quantified by g.l.c. mass spectroscopy using synthetic reference compounds. 2. R-(+)- and S-(-)-prolintane were synthesized from optically active phenylalanine. The metabolism of the enantiomers differs mainly in the quantitative amounts of metabolites. PMID- 1632105 TI - Disposition of bepridil in laboratory animals and man. AB - 1. The disposition and pharmacokinetics of bepridil (Bp) were studied in mouse, rat, rabbit, rhesus monkey, and man. Bp was essentially completely absorbed by all species. 2. Maximum plasma Bp concentrations were achieved within 2 h of drug administration. Linear but non-proportional, dose-related increases in the area under the curve (AUC) for plasma Bp vs. time were noted after increasing oral doses of Bp.HCl to rats (30-300 mg/kg) and monkeys (25-200 mg/kg). 3. Daily administration of Bp.HCl to rats (100 mg/kg per day for 15 days) and monkeys (200 mg/kg per day for 13 days) produced no statistically significant changes in Bp pharmacokinetic parameters. 4. Oral plasma clearance (CLp) of Bp was very low in man (ca. 0.93 l/h per kg) compared to experimental animals (14.8-63.8 l/h per kg). Terminal elimination half-lives were 1.5-2.0 h for mouse and rat, ca. 4.4 h for monkey and ca. 48 h for man. 5. Bp and a total of 12 metabolites were identified and quantified. Metabolite formation in the five species was adequately described by four interrelated pathways, namely, aromatic hydroxylation, followed by N-dealkylation, N-debenzylation, and N-acetylation. Metabolites produced by this pathway included 4-hydroxy-Bp, N-benzyl-4 aminophenol, 4-aminophenol, and N-acetyl-4-aminophenol. Comparison of the proposed pathways revealed qualitative similarity among species. PMID- 1632107 TI - The plasma pharmacokinetics of iophenoxic and iopanoic acids in goat. AB - 1. The comparative plasma pharmacokinetics of two organic iodine-containing compounds were evaluated in the goat for their suitability as markers in wildlife studies. 2. After oral administration of a single dose, the plasma elimination half-life for iopanoic acid was considerably more rapid (t1/2 of 1-2 days) than that of iophenoxic acid (t1/2 of 81 days). 3. Similar peak plasma concentrations were obtained after administration of iophenoxic acid (1.5 mg/kg) and iopanoic acid (25 mg/kg); however, the AUC0----infinity for iopanoic acid at doses of 25, 50, and 100 mg/kg were 201 +/- 39, 604 +/- 225, and 1292 +/- 721 (micrograms h/ml +/- SD), respectively, which were less than the value of 36,600 +/- 6387 for the oral administration of iophenoxic acid at 1.5 mg/kg. 4. Iophenoxic acid was chosen as a suitable marker because of its persistence at detectable concentrations in the plasma for 5 months. PMID- 1632106 TI - Disposition of minaprine in animals and in human extensive and limited debrisoquine hydroxylators. AB - 1. The disposition of 14C-minaprine was studied after oral administration of 5 and 20 mg/kg to rats, dogs and macaques, and of 200 mg to human volunteers with a genetic status of either limited or extensive hydroxylation of debrisoquine. 2. The drug was readily absorbed and a large proportion of the administered radioactivity was excreted within 48 h. The total excretion over 5 days ranged from 83% in monkeys to almost 100% in human with a status of extensive hydroxylators. 3. In the two limited hydroxylators Cmax values of total radioactivity in plasma were 4.6 and 3.7 mg equiv/l respectively. Those in the two extensive hydroxylators were 1.9 and 1.6 respectively. The highest value in the animal species was 8.1 in rats at a dose of 20 mg/kg. Plasma Cmax values of minaprine were 4.0 and 1.4 mg/l in limited hydroxylators and 0.35 and 0.23 mg/l in extensive ones. The highest value in the animal species was 2.7 mg/l in dogs treated with 20 mg/kg. 4. In rats and dogs, the ratios of the plasma AUC values for 20 mg/5 mg doses were close to those of the ratios of the doses administered, whereas in the macaque a slower clearance of radioactivity occurred with the higher dose (t 1/2 beta 5.5 h at 5 mg/kg dose versus 25.7 h at 20 mg/kg dose). 5. Marked species differences were observed in the metabolic pathways. The dog and limited hydroxylators showed higher levels of minaprine and its N-oxide (M4) whereas p-hydroxy-minaprine (M3) prevailed in monkey, rat and extensive hydroxylators. 6. In dogs only, seizures appeared within 10-15 min after dosage with minaprine at 20 mg/kg, when the concentrations of minaprine in erythrocytes (6.9 mg/l) and of M4 in plasma (0.40 mg/l) and erythrocytes (0.25 mg/l), were high. 7. The measurements and clinical observations indicate that onset of an adverse behavioural response in humans is unlikely at the dose of 200 mg. PMID- 1632108 TI - Involvement of FAD-dependent polyamine oxidase in the metabolism of milacemide in the rat. AB - 1. It has previously been established that monoamine oxidase (MAO)-B participates in the metabolism of milacemide [2-(pentylamino)acetamide]. Furthermore, in rats, inhibition of FAD-dependent polyamine oxidase (PAO) was found to decrease the urinary excretion of two milacemide metabolites, termed UK1 and UK2. 2. Using gas chromatography-mass spectrometry, UK1 was identified as oxamic acid and UK2 as 2 hydroxyacetamide, confirming that PAO is involved in the metabolism of milacemide. 3. Thus, two FAD-dependent amine-oxidizing enzymes, MAO and PAO, contribute to the metabolism of milacemide. Milacemide appears to be the first non-polyamine xenobiotic in the metabolism of which PAO participates. PMID- 1632110 TI - Differentiation of cytochrome P-450 inducers on the basis of 7-alkoxycoumarin O dealkylase activities. AB - 1. The high-affinity and total activities of 7-methoxycoumarin O-demethylase and of 7-ethoxycoumarin O-deethylase were measured in liver microsomes isolated from rats treated with prototypic inducers belonging to the main classes of microsomal enzyme inducers currently recognized. 2. Each inducer (with the exception of clofibrate which was ineffective) produced a unique induction profile, indicating the possibility of using these two enzymes, each measured at two substrate concentrations, for characterization of the inducing potential of novel xenobiotics. 3. Differences between p,p'-DDT and phenobarbitone in the induction profiles indicate that DDT may not be a pure 'phenobarbitone-type' inducer as has been proposed hitherto. PMID- 1632109 TI - Metabolism of 1,2,4-trichlorobenzene in rats: examination of thiol formation. AB - 1. More than 60% of oral doses of 14C-1,2,4-trichlorobenzene (ca. 21 mg/kg) administered to rats were excreted in bile as S-trichlorophenyl-mercapturic acid pathway metabolites. 2. The biliary metabolites were ultimately excreted in urine mainly as the isomeric mercapturic acids. 3. An acetylated glutathione conjugate was isolated as a major metabolite in bile (8% dose). The acetyl group was shown by mass spectrometry to be on the glutamyl moiety. 4. A glutamylcysteine conjugate of trichlorobenzene was also isolated from bile as a major metabolite (8% dose). 5. Trichlorothiophenols were deduced not to be intermediates or end products of enzymic metabolism of trichlorobenzene in rats because 14C-2,4,5 trichlorothiophenol dosed i.p. to rats was excreted as the S-glucuronide (17% dose) and as S-(methylsulphonyl-dichlorophenyl)-mercapturic acid (36% dose). PMID- 1632111 TI - Single- and multiple-dose kinetics of d-fenfluramine in rats given anorectic and toxic doses. AB - 1. High parenteral doses of a twice-daily schedule of d,l-fenfluramine (d,l-F) may cause long-lasting decrease of functional indices of brain serotoninergic neurones in rats. The single- and multiple-dose (b.i.d. x 4 days) kinetics of low (1.25 mg/kg) and high (12.5 mg/kg) subcutaneous (s.c.) doses of d-F, which accounts of the anorectic effects of the racemate, and its deethylated metabolite d-norfenfluramine (d-NF), were therefore examined and compared with those of pharmacologically effective oral doses (0.3-1.25 mg/kg) in rats. 2. There were dose-dependent alterations of kinetic parameters after s.c. and oral dosing, indicating that hepatic clearance of d-F in the rat can be saturated either by increasing the size of the single dose or during repeated dosing. Nonlinearity was also observed for d-NF. Consequently at high doses exposure of rat to the drug, as measured by the sum of area under the plasma concentration-time curve (AUC) of d-F and d-NF considerably exceeded that expected from simple dosage considerations, particularly with repeated administration of d-F. 3. Total exposure at the high doses considerably exceeded that at pharmacological doses, however, indicating an ample margin in favour of anorectic activity. The possibility that the long-term depletion of brain 5-HT by d-F and/or its metabolite d-NF may have relevance at the usual therapeutic dose, is discussed. PMID- 1632112 TI - Biotransformation of mianserin in laboratory animals and man. AB - 1. The biotransformation and excretion of the antidepressant mianserin were studied after oral administration of the labelled drug to rats, mice, rabbits, guinea pigs and humans. Mianserin was well absorbed and almost completely metabolized in all five species. 2. Major metabolic pathways of mianserin were p oxidation of the N-substituted aromatic ring followed by conjugation, and oxidation and demethylation of the N-methyl moiety, followed by conjugation. Direct conjugation of the N-methyl moiety was observed as a metabolic pathway specific for man. 3. Conjugated metabolites were isolated by h.p.l.c. and identified by 1H-n.m.r. and FAB spectrometry. Novel metabolites such as an N-O glucuronide in the guinea pig and an N-sulphonate in rat and guinea pig, were identified using these techniques. A quaternary N-glucuronide was found only in man. PMID- 1632113 TI - Inhibition of rat hepatic aryl sulphotransferase IV by dihydrodiol derivatives of benzo[a]pyrene and naphthalene. AB - 1. Although neither the (+)- nor (-)-enantiomer of trans-benzo[a]pyrene-7,8 dihydrodiol was a substrate for aryl sulphotransferase IV from rat liver, both enantiomers inhibited the enzyme-catalysed sulphation of 1-naphthalene-methanol with Ki values of 3.7 +/- 0.4 microM for the (+)-enantiomer, and 4.4 +/- 0.3 microM for the (-)-enantiomer. 2. Based on the magnitude of the Ki values, the binding affinity of these dihydrodiols for the aryl sulphotransferase was significantly greater than that for the corresponding phenolic derivatives of benzo[a]pyrene. That is 7-hydroxybenzo[a]pyrene and 8-hydroxybenzo[a]pyrene were both substrates for aryl sulphotransferase IV, with apparent Km values of 280 +/- 41 microM and 370 +/- 72 microM, respectively. 3. Both (+)- and (-)-trans naphthalene-1,2-dihydrodiols were also inhibitors of aryl sulphotransferase IV, but with higher Ki values than would be expected from previously determined apparent Km and Ki values for (R)-(-)- and (S)-(+)-1,2,3,4-tetrahydro-1 naphthols, respectively. PMID- 1632114 TI - [Effect of pirenzepine on motility of Oddi's sphincter]. AB - Pirenzepine (Gastrozepin) has a proven positive effect in the treatment of peptic ulcers by blocking the so called muscarinic acetylcholine receptors of the gastric glands. Reports of positive results with pirenzepine in the treatment of acute pancreatitis led to new discussions about its biological effects. It is thought that there are three ways by which pirenzepine acts in the pancreas. It decreases enzymatic secretion and it increases the secretion of sodium bicarbonate and water. Furthermore, it is said to have a spasmolytic effect on the sphincter of Oddi. To prove this spasmolytic effect we performed endoscopic manometry at the sphincter of Oddi with intubation of the pancreatic duct in 12 healthy patients. After two minutes of manometric registration of the normal sphincter activity 6 patients received 10 mg pirenzepine i.v. while a control group of 6 patients received 2 ml of 0.9% NaCl i.v. During the next 5 minutes the basal pressure of the sphincter, the amplitude of concentrations, as well as their frequency and duration were monitored. There were no changes noticed in the placebo group. However, pirenzepine caused a considerable decrease of the 4 manometric parameters of the sphincter of Oddi in all patients. Within 5 minutes the basal tonus fell from 14.3 +/- 5.1 mm of mercury to 9.0 +/- 6.0 (p less than 0.01). The frequency of contractions dropped from 5.8 +/- 2.7 per minute to 2.0 +/- 2.1 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632115 TI - [Cavernous liver hemangioma with arterio-portal fistula]. AB - Evidence of a cavernous hemangioma of the liver with fistula between hepatic artery and the portal vein of a 52 year-old woman with colickly upper abdominal pain and ascites was obtained using Duplex-Doppler-ultrasound. The diagnosis was confirmed by selective arteriography. After ligation of the left hepatic artery clinical symptoms abated. The cavernous hemangioma was followed up over 7 1/2 years with ultrasound. Ultrasound has been shown to be a valuable test for diagnosis and follow up of cavernous hemangioma. PMID- 1632116 TI - [Applicability of CCK receptor antagonists in physiologic and therapeutic studies]. AB - The development of potent and specific CCK-receptor antagonists made it possible to evaluate the physiological role of CCK for various gastrointestinal functions. The results of these studies show that CCK is the hormone which principally mediates meal-induced gallbladder emptying. In addition, CCK appears to play an important role in maintaining the fasting muscular tone of the gallbladder. In contrast, CCK-antagonists could inhibit only about 50% of the meal-stimulated pancreatic exocrine secretion. Because of their marked relaxing effect on the gallbladder, CCK-antagonists might become an important clinical tool for treatment of gallbladder spasms and colics. On the other hand, long-term application of CCK-antagonists will increase the risk of stone formation in the gallbladder. CCK-antagonists also had beneficial effects in some animal models of acute pancreatitis. As yet, it is unclear whether CCK-antagonists might become useful for the treatment of human pancreatitis. Since CCK-antagonists only slightly inhibited pancreatic growth, it is unlikely that they will exert major inhibitory effects against growth of pancreatic carcinoma. CCK-antagonists failed to alter gastric emptying of a normal mixed solid-liquid meal, but accelerated gastric emptying of purely liquid meals. Thus, CCK-antagonists are not likely to become useful agents to treat alterations of gastric emptying. The studies with CCK-antagonists further showed that CCK plays only a minor role in the regulation of the motility of the small and large intestine. CCK is probably not involved in the regulation of the gastrocolonic response after a meal. Some reports indicate that CCK-antagonists might increase colonic transit and might therefore be useful to treat constipation. PMID- 1632117 TI - [Do patients with acute Crohn disease profit from enteral nutrition with oligopeptide diet?]. PMID- 1632118 TI - [Octreotide in intestinal pseudo-obstruction?]. PMID- 1632119 TI - [25th annual meeting of the Austrian Association for Gastroenterology and Hepatology. Vienna, 12-13 June, 1992. Abstracts]. PMID- 1632120 TI - [Letter to the Journal of Gastroenterology. Comment on the article "Senna or bisacodyl before lavage preparation for colonoscopy: prospective randomized comparative study", by D. J. Ziegenhagen, E. Zehnter, W. Tacke, T. H. Gheorghiu, W. Kruis]. PMID- 1632121 TI - Stress related diagnosis: increased admittance to hospital during unannounced warfare in Croatia? PMID- 1632122 TI - [Use of ERCP in pancreatic diseases]. PMID- 1632123 TI - [The structure of fish helminth populations]. AB - Typification and some qualitative characteristics of populations of the fish helminths are given which allow to explain some peculiarities of their numbers, genetical interrelations, action of immunological factor. Simplification of the structure of helminth populations provokes large fluctuations of the helminths number. Differences in the structure of helminth populations are to be considered as one of mechanisms of development of stability of parasitic system. PMID- 1632125 TI - Modelling of the cardiac electrical field. PMID- 1632124 TI - [The evolutionarily optimal rates of body development. The age of onset of sexual maturity and species-specific longevity as the parameters optimized during evolution]. AB - Dynamics of biological community of the "resource--consumer" type considering age structure of consumer population is described by a system of differential equations with special derivatives. On the basis of such a model, a competition model for non-crossing populations with different individual development rates is elaborated. It is shown that only a population with development rates maximizing the Malthusian function (reaching zero value at the equilibrium state of the system) is able to survive under competition for food resources. Equilibrium density of the resources is provided being minimal. Thus maximum energy influx into the population is gained. Search algorithm of evolutionary values of puberty, age and maximal longevity of individuals belonging to the consumer population is proposed. Analytic dependence of maximal longevity on environmental factors and some other parameters are found. Aging is considered to be mechanism leading to death while individual approaches evolutionary optimal longevity. PMID- 1632126 TI - Angiographic coronary artery lesion morphology and pathogenetic mechanisms of myocardial ischemia in stable and unstable coronary artery disease syndromes. AB - The angiographic morphology of coronary artery stenoses was studied in 160 patients referred for diagnostic coronary arteriography. Three groups of patients were studied: 60 patients with stable angina, 78 patients with unstable angina and 22 patients with a recent myocardial infarction. Complex lesions were more frequently observed in patients with unstable angina (59%, p less than 0.001) and in patients with a recent myocardial infarction (54%, p less than 0.05) then in patients with stable angina (25%). Angiographic signs suggestive for the presence of intravascular thrombi were almost exclusively observed in the patients with unstable angina (34%, p less than 0.001) and in the patients with a recent myocardial infarction (27%, P less than 0.001) and were almost completely absent in the patients with stable angina (1.5%). The high prevalence of complex coronary artery lesion morphology and of intravascular thrombi observed in patients with unstable angina or with a recent myocardial infarction emphasizes the important role of intima disruption and of subsequent thrombosis in the pathogenesis of myocardial ischemia in those unstable syndromes of ischemic heart disease. PMID- 1632127 TI - Influence of upright exercise on pulmonary hemodynamics in left heart failure. AB - Studies in severe chronic stable heart failure (HF) indicate that pulmonary resistance might remain unchanged during exercise and could subsequently contribute to limitation in exercise capacity of these patients. We assessed the possible role of the exercise decreases in mixed venous oxygen tension on this phenomenon in fifteen patients with chronic congestive heart failure (N.Y.H.A. functional classes II to IV) who underwent a symptom-limited treadmill exercise test with hemodynamic monitoring as well as repeated arterial and mixed venous blood gas analysis. For all patients there was an increase in cardiac output (from 3.7 +/- 0.2 to 6.7 +/- 0.5 l/min, p less than 0.001) and pulmonary wedge pressure (from 16 +/- 2 to 31 +/- 3 mm Hg, p less than 0.001) along with exercise with highly significant decrease in total systemic resistance and no significant (from 25.6 +/- 1.5 to 15.8 +/- 1.0 U, p less than 0.001) changes in pulmonary vascular resistances. Arterial blood oxygen tension increased from 86 +/- 3 to 99 +/- 3 mm Hg (p less than 0.001) and mixed venous oxygen tension (PvO2) decreased from 33 +/- 1 to 22 +/- 1 mm Hg (p less than 0.001). Changes in pulmonary vascular resistance during exercise were inversely related to changes in PvO2 (r = -0.61; p less than 0.05). We conclude that the observed decrease in PvO2 might be a determinant of unchanged pulmonary vascular resistance during treadmill exercise test in severe heart failure patients. PMID- 1632128 TI - Handgrip-apexcardiographic test: a new mode of detecting patients with silent exercise-induced myocardial ischemia. AB - There are no simple noninvasive stress tests for detecting silent myocardial ischemia by assessing left ventricular (LV) diastolic abnormalities which are known to occur early on the onset of every ischemic episode. It has been proved that the LV apexcardiogram (ACG) reflects the LV pressure curve in early and late diastole and can be recorded during isometric handgrip (HG) exercise. To determine the clinical validity of HG-ACG-Test (HAT) in identifying patients with silent ischemia, 16 patients (8 with prior infarction) with angiographically documented coronary artery disease, positive treadmill electrocardiographic test and without symptoms were examined. According to the largest and lowest individual values in 253 healthy volunteers, the positivity of HAT was defined by the presence of at least one of the criteria: 1) The relative A-wave to total height of ACG during or/and after HG greater than 21%. 2) The total ACG relaxation time (TART) during HG longer than at rest and also longer than 143 ms or/and the heart rate corrected TART during HG less than 0.14, or 3) the combined index of overall diastolic function DATI (= diastolic amplitude time index) during HG less than 0.27. Based on this definition 14/16 (sensitivity: 88%) patients showed a positive test result. It is concluded that, using new definitions of positivity, HAT shows a high sensitivity for detecting patients with proved silent ischemia providing, thus, providing a new simple clinical tool for the identification of these patients. PMID- 1632129 TI - Invasive and echocardiographic evaluation of non-Q myocardial infarction with isolated stenosis of descending anterior coronary artery. AB - Prognostic and clinical characteristics of acute myocardial infarction (AMI) can usually justify surgical and/or angioplastic approach if the residual ventricular function is still good. Multivessel disease frequently complicates results interpretation. We studied with 2D echocardiography and coronary angiography two groups of patients with one vessel stenosis located on anterior descending (AD) and previous AMI (means 19 days): 23 patients with spontaneous non-Q infarction (group 1), and 23 patients with Q infarction. Left ventricular function was better in group 1. Percent occlusion of AD was lower in group 1 and angiographic AD caliber was significantly higher. Differences between groups were much more evident in subgroups with proximal stenosis of AD: patients of non-Q subgroups had very good left ventricular function but frequently had post-AMI instable angina (88%). Our results underline the usefulness of aggressive diagnostic and therapeutic approach in non-Q AMI, because of higher amount of myocardium at risk. PMID- 1632130 TI - Noninvasive evaluation of asymptomatic athletes with cardiac murmur. AB - The increasing number of amateur sportsmen enhances the need for a correct evaluation of subjects suspected of overt and mild cardiac disease. Out of 4000 athletes, 72 subjects were clinically preselected by the sport doctor during an annual routine examination. They were studied with mono and 2D echo, pulsed color (PW) and continuous wave Doppler. Five asymptomatic patients are reported with congenital or acquired valvular diseases. PMID- 1632132 TI - Mechanocardiographic effects of an elevated central venous pressure. AB - Since 1985 we demonstrated that the increase of left ventricular mean diastolic pressure shortens the interval existing between the onset of the electrocardiographic P-wave and the onset of the left apexcardiographic "a"-wave (Aubert et al., 1981; Mortarino et al., 1985). In particular we showed that left P-"a" time interval shortens below 100 msec when left ventricular mean diastolic pressure rises above 12 mmHg. Our results thus substantiated the previous reports related to the P-4th heart sound shortening and 4th heart sound--1st heart sound increase occurring in patients with left ventricular failure (Shapira et al., 1982). In that same period, Kesteloot and collaborators showed a direct relationship between the velocity of appearance of the right internal jugular pulse (JVP) waves and the value of central venous pressure (CVP) (Minten et al., 1985). Moreover the range of variability of the right P-"a" interval (which is the time elapsing between the onset of the electrocardiographic P-wave and the onset of the "a"-wave on the JVP tracing) is, in adult subjects, of similar magnitude of the left P-"a" interval (respectively 60-140 msec (Fishleder, 1968) and 80-160 msec (Mortarino et al., 1985) suggesting a symmetric effect of an elevation of diastolic pressure on left and right P-"a" intervals. We therefore decided to test this hypothesis in a group of patients. PMID- 1632131 TI - Noninvasive assessment of the relationship between cardiac and autonomic function in diabetes. AB - In order to assess a possible relationship between left ventricular (LV) function and cardiac autonomic involvement in type-1 insulin dependent diabetes, we performed M-mode echocardiograms and autonomic function tests in 21 patients (mean age +/- SD, 38 +/- 11 years, range 18-55, 16 male and 5 female). In 7 patients and in 21 age-matched controls the echocardiogram was also recorded before and during handgrip. At rest, ventricular function abnormalities were found only in 4 subjects, and no significant correlation was found between echocardiographic parameters and autonomic function tests. Unlike controls, during handgrip diabetic subjects failed to increase peak Vcf and peak filling rate, and increased their left ventricular end-systolic diameter. The changes in LV parameters during handgrip were significantly correlated with resting autonomic function tests (p less than 0.025). Our results suggest that resting cardiac function may be normal in diabetics despite high incidence of abnormal autonomic tests. Latent abnormalities of left ventricular function can be unmasked by acute haemodynamic challenges such as handgrip, and are correlated with abnormalities in autonomic function tests. PMID- 1632133 TI - [Enteroscopy: methods and results]. AB - Recent advances in the instrumentation and techniques of enteroscopy now permit examination of the small bowel. This report is on the use of a prototypic small bowel enteroscopy to investigate patients with gastrointestinal bleeding of obscure origin. We used the sonde-type enteroscope (Olympus Corp.) that migrates distally responding to peristaltic activity. This instrument has neither tip deflection controls nor interventional capability. Small bowel enteroscopy was performed in 17 patients. Arteriovenous malformations were visualized in 5 patients but three of them suffered from Rendu-Osler disease. Small bowel enteroscopy can be useful in the evaluation of patients with gastrointestinal bleeding of obscure origin. However, patients must be well selected on basis of negative routine examinations because this method is time-consuming. PMID- 1632134 TI - [Role of arteriography in the assessment and treatment of hemorrhagic diseases of the small intestines]. AB - We present the indications and usefulness of visceral angiography for diagnostic and therapy in patients with gastrointestinal haemorrhage. This is based on the results of a retrospective study of 265 angiographies for gastrointestinal bleeding. In fifty one cases an extravasation was seen and in one hundred and four patients a possible etiology for the gastrointestinal hemorrhage was suspected from indirect signs. In 19 cases, an embolization was performed with good result in 16 (84%). PMID- 1632135 TI - [Celiac disease in adults: clinical aspects--role of endoscopy]. AB - Adult coeliac disease has a broad clinical spectrum and remains undetected for years. Among subclinical deficiency states, attributable to coeliac enteropathy, combined iron and folic acid malabsorption is predominant. An unexplained recurrent iron anaemia is an indication for small intestinal biopsy. Gastro intestinal disorders are present in only 50% of the cases. Coeliac disease is frequently associated with other major histocompatibility complex (MMC)-linked diseases which are mediated by immunological mechanisms: dermatitis herpetiformis, oral ulcerations, IgA nephropathy, rheumatoid arthritis, sarcoidosis. Dermatitis herpetiformis is a useful model for examination of the spectrum of mucosal changes that typify gluten sensitivity and subliminal lesions without villous atrophy. An increased interest is devoted to the intra-epithelial T-lymphocyte population, not only in the small intestine, but at the level of the stomach and the colon. A "rectal challenge" test has been proposed for detecting gluten sensitivity in coeliac patients. Such a test could be an original method of screening, reducing so the need of small intestinal biopsy. The preliminary results are to be confirmed. Until now, jejunoscopy remains mandatory for the diagnosis and the survey of intestinal lesions related to coeliac disease. PMID- 1632136 TI - Coeliac disease "anatomic pathology". AB - The microscopic diagnosis of coeliac disease is discussed. The small intestinal mucosal lesions observed in coeliac disease consist of a combination of epithelial alterations and inflammatory lesions starting with pre-infiltrative changes. In the early (?) changes an increase of lymphocytes is noted. The interactions probably finally lead to destruction or atrophy of the villi. PMID- 1632137 TI - Serological aspects of coeliac disease. AB - We have evaluated the sensitivity and specificity of serum anti-gliadin, anti reticulin and anti-endomysium antibody determinations for the diagnosis of coeliac disease. Serum samples from 54 children and 9 adults with untreated coeliac disease were analysed for anti-gliadin antibodies and compared to the results obtained for 111 non coeliac controls (72 children, 39 adults) and 221 healthy blood donors. This yields sensitivities of 87% and 86% for IgA and IgG antibodies. Specificities were respectively of 95.5% and 91%. Anti-reticulin and anti-endomysium IgA were analysed in a more limited number of sera. Specificity of both tests was of 100% for the IgA class of antibody. However sensitivity was only of 64% for anti-reticulin IgA but was of 100% for anti-endomysium IgA. These results indicate that combination of anti-gliadin antibodies (IgA and IgG), anti reticulin and anti-endomysium IgA may be recommended as screening tests to better select patients suspected of coeliac disease for jejunal biopsy. PMID- 1632138 TI - [Primary hypogammaglobulinemia in adults]. AB - Intermittent or chronic diarrhea may be the initial symptom of hypogammaglobulinemia. In adult, that corresponds most frequently to common variable immunodeficiency. The pathogenesis of this syndrome is still undetermined. Diagnostic criteria are discussed as well as the therapeutic approach that can avoid multiple complications. PMID- 1632139 TI - Small bowel amyloidosis, pathology and diagnosis. AB - The authors describe clinical findings, radiological aspects and histological characteristics of small bowel amyloidosis in 8 patients. Pathogenesis of the small bowel related symptoms and diagnostic procedures are discussed. PMID- 1632140 TI - [Therapeutic approach in intestinal lymphoma]. AB - Primary gastrointestinal lymphoma (Maltoma) represent between 1 to 4% of all gastrointestinal malignancies. Disseminated cases are hard to differentiate with advanced stages of peripheral non-Hodgkin's lymphoma. The discovery of specific adhesion molecules could resolve this physiopathological problem. The prevalence of small bowel lymphoma is higher in Middle-East and South Africa (50% vs 30%) than in West Europe because of the occurrence of the immunoproliferative small intestinal disease (IPSID). Multicenter locations and disseminated forms of small bowel lymphoma yield curative surgery uneasiness. An algorithm of treatment, including surgery, mono or polychemotherapy, colony-stimulating factors, and interferon, taking into account histological and clinical stages is proposed. Because of the rarity of the disease, treatment must be improved by activation of international multicenter randomized trials. PMID- 1632141 TI - Glaxo Prize 1992. Assessment of lipid peroxidation in humans by breath pentane output measurement. PMID- 1632142 TI - Endoscopic treatment of esophagogastric varices. AB - We report our current management of variceal bleeding with endoscopic sclerotherapy. We emphasize the importance of resuscitation and of recording at time zero and within the first 72 hours clinical and laboratory indicators, as these influence the management of these patients. Primary sclerotherapy using Histoacryl for active bleeding and Ethoxysclerol for recent bleeding should be performed as soon as the patient is stable hemodynamically. As we have identified factors related to the severity of hemorrhage and of liver failure degree which can predict early failure of sclerotherapy, patients presenting with these findings should be, in the future, referred quickly toward alternative therapies among which non-surgical intrahepatic shunt appears a promising modality. PMID- 1632143 TI - Non-surgical management of achalasia. AB - Pneumatic dilatation of the cardia is an effective procedure to treat patients suffering from achalasia. Eighty percent of these patients can be expected to have excellent or good results for 6 years after the first dilatation. A repeat dilatation should be performed as soon as the patient has recurrent symptoms, usually every 2 years. Calcium channel blockers (nifedipine and verapamil) or nitrates (isosorbide dinitrate) decrease LES pressure but do little to the clinical symptomatology of patients with achalasia; however such drug therapy may be tried as an adjunct in patients who remain symptomatic after pneumatic dilatations or myotomy. Pneumatic dilatation and surgical myotomy both reduce LES pressure; with pneumatic dilatation, enough residual LES pressure is retained to prevent gastroesophageal reflux. Indeed, reflux esophagitis seems to occur more often after surgery than after forceful dilatations. We think that pneumatic dilatation should be performed as the primary therapy and surgery reserved for the failures of this procedure. PMID- 1632144 TI - Treatment of peptic ulcer severe bleeding. AB - The success of a defined management policy op peptic ulcer haemorrhage which incorporates endoscopic therapeutic intervention depends on the early identification of a high risk group of patients and a high risk group of ulcers. The high risk group of patients consists of those likely to experience further bleeding on the basis of clinical prognostic indicators: shock and severe anaemia on admission and the pattern of bleeding; or tolerate rebleeding and emergency surgery poorly: patients over 60 years and those with associated disease. UGI endoscopy should be performed early (within 6-12 hours) in this group in order to identify the bleeding point and provide prognostic information regarding the risk of further haemorrhage. Peptic ulcers with major stigmata of recent bleeding (spurting or non-bleeding visible vessel) have high risk of rebleeding, the risk is even greater when major stigmata of recent haemorrhage (SRH) are associated with shock on admission. Patients with such ulcers should be monitored intensively and receive endoscopic haemostatic treatment in order to terminate active haemorrhage or prevent rebleeding thereby avoiding the need for emergency surgery with its attendant morbidity and mortality. Patients with ulcers with minor or no SRH have a very low risk of rebleeding and don't require intensive monitoring or endoscopic treatment and can be discharged from hospital early. Ulcers which cannot be completely characterized have an intermediate risk of rebleeding and should be managed as high risk lesions. Secondary to the anatomy of the visible vessel any haemostatic endoscopic treatment should be applied around, but avoiding, the sentinel clot. Well-designed randomized controlled trials of endoscopic haemostatic treatment of peptic ulcer haemorrhage in which stratification of risk was based on the SRH, have demonstrated for non-bleeding vessel a significant reduction in rebleeding and in emergency surgery, for spurting bleeding benefit was found only for the rebleeding risk. No advantage was demonstrated in each group of patients in term of mortality. Such studies also demonstrate the superiority of the Nd:YAG laser over the Argon laser. Perforation is a rare complication of Nd:YAG laser photocoagulation (less than 1%). Precipitation or aggravation of arterial haemorrhage during treatment of a visible vessel, as a result of a direct hit, is a more frequent complication (0 29%). Further laser treatment is successful in terminating 75% of these induced bleeds, the remainder requiring surgery. Preinjection of the ulcer with adrenaline does not appear to prevent this complication.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1632145 TI - Clinical significance of pancreas divisum. AB - Pancreas divisum (PD), a congenital anatomic variant consisting of a separate pancreatic ductal system, is diagnosed in nearly 10% of patients for whom a successful pancreatogram was obtained. The relationship between PD and pancreatic disease is discussed since 1976. Some authors, reporting a higher incidence of pancreatitis in patients having two separate pancreatic ducts, proposed the concept of relative outflow obstruction of pancreatic juice through the accessory papilla. Based on the literature data and on our own experience, this review asserts that there is no definite evidence for PD being associated with a significantly risk of idiopathic pancreatitis. Discrepancies between epidemiological series could be explained by selection biases leading to an apparent association of PD and pancreatitis. An objective assessment of accessory papilla stenosis in patients with PD is not clearly available to give consistent results. Although controversies persist with regard to the actual abnormality of PD and the presence of stenosis into the accessory papilla, several endoscopic and/or surgical procedures have been proposed in an attempt to correct what is thought to be a stenosis of the orifice of the dorsal duct. More than 300 patients have been treated until now with variable and unpredictable results, these treatments are not devoid of complications. We conclude that PD should be considered as a frequent coincidental anatomic variant having no clinical significance in the great majority of patients and not requiring systematic further therapy. PMID- 1632147 TI - Punitive damages. PMID- 1632146 TI - Operative colonoscopic endoscopy. AB - There are several conditions where operative colonoscopy is useful. Acute colonic pseudo-obstruction or Ogilvie's syndrome is characterized by a acute distension of the colon. Although medical management may be sufficient in many cases, endoscopic decompression must be performed when colonic distension is greater than 12 cm. Insertion of decompression tube to avoid rapid recurrence seems to be adequate. In case of massive lower intestinal hemorrhage, colonoscopy seems to be more accurate than mesenteric angiography. Such endoscopic examination requires an experienced endoscopist. Colonoscopic polypectomy has become the standard method for removal of colonic polyps. Factors influencing the rate of complications have been studied. While the number of complications was very low, we have observed that all the major hemorrhages were immediate when the blended current was used, but delayed when the pure coagulation current was applied. Endoscopic laser photocavitation is a valuable palliative method treating rectal adenocarcinoma in well selected patients. Indeed, if the patients survive sufficiently long after initial therapy, it becomes increasingly difficult to achieve persistent palliation with laser therapy. PMID- 1632149 TI - The laryngeal mask airway in the United States. PMID- 1632148 TI - Monitoring compliance: a sensitive indicator of change. AB - This article is the seventh in a series designed to help anesthetists appreciate the clinical applications of equipment and monitoring systems. The use of a new technology for monitoring compliance during general tracheal anesthesia techniques is presented along with an explanation of the added clinical benefits of visually monitoring patients' compliance compared to estimating compliance by feeling the tension on the rebreathing bag. PMID- 1632150 TI - U.S. Food and Drug Administration safety alert: cauda equina syndrome associated with use of small-bore catheters in continuous spinal anesthesia. PMID- 1632151 TI - New HCFA carrier manual instructions on Medicare payment. PMID- 1632152 TI - Health Care Financing Administration Medicare carriers manual. New implementing instructions for Medicare payment for anesthesia services. PMID- 1632153 TI - Criteria comparison of accreditation. Report of the National Commission on Nurse Anesthesia Education. PMID- 1632154 TI - The effect of knowledge of learning styles on anxiety and clinical performance of nurse anesthesiology students. AB - This study examined how students' knowledge of their learning styles affected their anxiety and clinical performance. In a graduate program of nurse anesthesiology with a sample size of 43 students, results indicated that, over time, students who were aware of their learning styles demonstrated less anxiety than those who were not. Knowledge of learning styles also improved clinical performance in the cognitive and affective domains. Recommendations for schools of nurse anesthesiology are discussed. PMID- 1632155 TI - AANA Journal course: update for nurse anesthetists--monitoring the brain for hypoxic events. AB - Monitoring of brain oxygen content is highly desirable as this organ is highly intolerant to hypoxia from a variety of possible etiologies, many of which can occur during the administration of anesthesia. Most of the modalities directed at brain oxygen monitoring are highly technical and currently are in various stages of evolution worldwide. These approaches include those which access brain oxygen content by both direct and indirect means. This lesson reviews the major areas of research currently underway and suggests that we should be optimistic that this technology may be available to us clinically in the foreseeable future. PMID- 1632156 TI - Side effects of morphine patient-controlled analgesia and meperidine patient controlled analgesia: a follow-up of 500 patients. AB - Many physicians, Certified Registered Nurse Anesthetists (CRNAs), and registered nurses have the clinical impression that either morphine sulfate or meperidine hydrochloride is a better drug to control postoperative pain. In this study, we evaluated pain relief and side effects for these two drugs to assess their potential differences. CRNAs conducted a structured interview of 500 female patients 24 hours after major gynecologic, urologic, or breast surgery. Patients' responses on 4-point scales of none, mild, moderate, and severe were collected for pain intensity, degree of nausea, severity of vomiting and itchiness, and degree of sedation experienced since the operation. There were 91 patients who received morphine patient-controlled analgesia (PCA) and 409 patients administered meperidine PCA. No statistically significant differences for pain intensity, degree of nausea, severity and incidence of vomiting, or degree of sedation were found. However, a significant difference was found in the incidence rates of mild itchiness, which occurred more frequently in the morphine PCA group (P less than .001). Patients vomited more often after vaginal hysterectomy than patients having laparotomy, major oncology, or tuboplasty surgeries (P less than .05), and vaginal repair patients reported more vomiting than patients having major oncology or tuboplasty surgeries. Clinical impressions that either morphine or meperidine should be the preferred treatment for patients following gynecologic operations was not found by a 24-hour review of 500 patients for pain relief and side effects. Although mild itchiness occurred more frequently in the morphine PCA group, treatment was rarely necessary. PMID- 1632157 TI - Adenosine: novel antiarrhythmic therapy for supraventricular tachycardia. AB - Adenosine (Adenocard) is a unique new agent for the acute treatment of paroxysmal supraventricular tachycardia (PSVT). Administered by intravenous bolus, it has an onset and duration measured in seconds and greater than 90% efficacy. Its primary effect is to slow atrioventricular nodal conduction, thus converting reentrant forms of PSVT to normal sinus rhythm. Side effects quickly dissipate without treatment because of the short duration of action. Other uses include diagnosis of broad or wide QRS complex tachycardias and controlled intraoperative hypotension. Its short duration and high efficacy in converting select forms of PSVT make adenosine an excellent alternative to verapamil in patients with compromised hemodynamics. This article will review the clinical use and anesthetic implications for the administration of this drug. PMID- 1632158 TI - Negative aspiration for cerebral spinal fluid does not assure proper placement of epidural catheter. AB - Inadvertent subarachnoid injection of a local anesthetic during the conduct of epidural anesthesia may have a devastating effect on the patient. The incidence of dural puncture with an epidural catheter has been reported to range from 0.5% to 0.9%. This case report demonstrates that, despite negative aspiration of cerebral spinal fluid from the catheter, subarachnoid injection of a local anesthetic can occur. PMID- 1632159 TI - Ketorolac tromethamine: a nonsteroidal anti-inflammatory analgesic used as an adjunct for general anesthesia. AB - This case report describes a general anesthetic where ketorolac tromethamine was used instead of a narcotic. The patient was a 37-year-old male, ASA II category, who underwent general anesthesia for a cholecystectomy. The drug is discussed in terms of preoperative, intraoperative, and immediate postoperative effects. During the preoperative phase, no effect was demonstrated. Intraoperatively, the drug performed poorly to attenuate responses to intense stimulation as noted by an increase in pulse and blood pressure of greater than 20% during intubation, incision, and abdominal wall retraction. During the immediate postoperative phase, the drug performed well to provide analgesia related to incisional pain. Ketorolac has not been previously discussed in terms of intraoperative uses. The mechanism of action by which it provides analgesia is through the inhibition of prostaglandin synthesis. It is similar in structure to the other nonsteroidal anti-inflammatory drugs and may offer certain advantages over traditional agents used to provide analgesia, including the absence of respiratory depression, addictive potential, euphoria, a decrease in gastric motility, and cardiovascular effects. These properties may help in the management of certain types of patients who are at risk for respiratory depression or in those who have a contraindication to narcotics. PMID- 1632160 TI - Epinephrine as an adjuvant to amino-amide local anesthetics does not prolong their duration of action in infraorbital nerve block in the rat. AB - The effects of epinephrine as an adjuvant to local anesthetics were studied in the rat infraorbital nerve block (IONB) model, using solutions of 0.5% prilocaine, 0.5% mepivacaine, 0.125% bupivacaine or 0.125% ropivacaine in 50 mmol/l tris-hydroxymethylaminomethane (THAM) tested both without and with epinephrine (EPI) added at 2, 4, 8 or 16 micrograms/ml. Solutions of THAM and EPI in normal saline did not induce IONB. THAM-buffered solutions of bupivacaine induced IONB of longer duration than bicarbonate-buffered solutions. Intensity of block during onset was increased only when EPI at 2 and 16 micrograms/ml was included in bupivacaine solutions. The duration of block induced by prilocaine, bupivacaine and ropivacaine was not significantly prolonged by addition of EPI at any of the concentrations tested. Only at a concentration of 16 micrograms/ml did EPI significantly prolong the duration of mepivacaine-induced block (+48%). Low concentrations of EPI in solutions of bupivacaine and ropivacaine significantly reduced their duration of action by up to 22% and 57%, respectively. It is concluded that the duration of action of local anesthetics in buffered solutions is only moderately affected by the inclusion of EPI, the effects differing only slightly from one to another. The efficacy of EPI as an adjuvant would seem to be governed by factors affecting the local disposition of the main drugs, such as non-specific binding, buffering of solutions and tissue pH. PMID- 1632161 TI - The effects of brain temperature on temporary global ischaemia in rat brain. A 31 phosphorous NMR spectroscopy study. AB - 31-Phosphorus magnetic resonance spectroscopy was used in a rat model of 10 min severe incomplete forebrain ischaemia (2-vessel occlusion with hypotension) to assess the effect of mild brain hypo- and hyperthermia (+/- 2 degrees C) on intracellular pH and high energy phosphates. In three experimental groups intracerebral temperature was maintained at levels of 34, 36 and 38 degrees C during ischaemia and early reperfusion. The steady level of intracellular pH during ischaemia was 6.63, 6.58 and 6.53 in the 34, 36, and 38 degrees C groups, respectively. The rate of initial recovery of intracellular pH in reperfusion was 0.046 +/- 0.012 pH units per min (+/- s.d.) in the 36 degrees C group compared to 0.056 +/- 0.010 (+/- s.d., P less than 0.05) in the 34 degrees C group and 0.032 +/- 0.009 (+/- s.d., P less than 0.01) in the 38 degrees C group. The recovery in early reperfusion of phosphocreatine and ATP was slower in the 38 degrees C group compared to the other groups. The findings were consistent with recent studies, suggesting that even mild hypothermia may afford protection to the ischaemic brain, and furthermore indicate that mild hyperthermia as fever or even subfebricity may be deleterious for the outcome in stroke patients. PMID- 1632162 TI - Adenosine modulates vascular resistance and fluid filtration in isolated rat lungs. AB - In adult respiratory distress syndrome, a major concern is to reduce increments in pulmonary vascular resistance (PVR) and maintain the patency of lung microvessels. We have investigated the effects of adenosine, a potent systemic vasodilator, on PVR and fluid filtration rate (FFR) in isolated blood-perfused rat lungs. The preparations were undamaged or subjected to fat emulsion-induced injury simulating ARDS. In undamaged lungs adenosine caused a significant dose dependent reduction of hypoxia-induced increases in PVR. Furthermore, the increase in FFR upon elevation of left atrial pressure by 0.77 kPa was significantly hampered by adenosine, 24 nmol.ml-1.min-1. Employing the same rate of infusion, adenosine, in a group of injured preparations, significantly reduced the rise in PVR towards baseline and completely abolished the further increase upon a superimposed injection of serotonin. In another series of preparations with lung injury randomly assigned to an adenosine group and a control group, adenosine significantly reduced FFR. Thus, adenosine, even when infused at low rates, reduced increments in PVR and fluid filtration, both in undamaged and in fat emulsion-injured isolated lungs. PMID- 1632163 TI - Failure of hypertonic saline to resuscitate intestinal ischemia shock in the rat. AB - The effects of resuscitation with hypertonic saline (HS), administered as a bolus injection or infusion, were studied in a model of intestinal ischemia shock in rats. The model is characterized by severe intestinal mucosal lesions, release of cardioinhibitory substances and endogenous opioid peptides, and it results in high mortality rates. The blood pressure improved after HS given as an infusion for 1 h. The effects on blood pressure of HS given as a bolus and of normotonic saline (NS) were not significant. Plasma volume was not different from unshocked control animals in either HS infusion or NS infusion groups 2 and 4 h after infusion. Liver metabolic consequences of intestinal shock did not differ comparing the HS and NS groups, and the same result was found concerning the mucosal lesions in the small intestine. The 7-day survival decreased in the HS infusion group (14%) compared to untreated shock (46%) or NS infusion (54%) groups. We conclude that HS failed to resuscitate intestinal ischemia shock. These experiments indicate that HS treatment could even, in contrast to previous reports on hemorrhagic shock, be disadvantageous or dangerous in shock states characterized by extensive tissue injury. PMID- 1632165 TI - Gas exchange as monitored in mixed venous and arterial blood during experimental cardiopulmonary resuscitation. AB - Nineteen anaesthetized piglets were investigated. After catheterization and a stabilization period, ventricular fibrillation was induced with a transthoracic DC shock, after which a 10-min period of cardiopulmonary resuscitation (CPR) took place. CPR included manual chest compression and mechanical ventilation with pure oxygen. After 1 min of CPR, an infusion of alkaline buffer was begun and completed within 5 min. A total of 50 mmol of either sodium bicarbonate (n = 6) or tris buffer mixture (n = 7) were given. These two groups were compared with a third control group (n = 6) receiving the same volume of normal saline. After 8 min of CPR all animals were given 0.5 mg adrenaline i.v., and after 10 min DC shocks were used to revert the heart back to normal sinus rhythm. Our results demonstrate that blood flow and not ventilation is the limiting factor for the efficient disposal of CO2 during CPR. This also applied when the demand for CO2 transport was increased by administration of sodium bicarbonate. The respiratory exchange ratio increased 1.9-fold, indicating that the transport of carbon dioxide was less affected than that of oxygen. The estimated alveolo-arterial oxygen tension difference, shunt, and overall ventilation/perfusion ratio increased, creating an inverse hyperbolic relationship between arterial PCO2 and PO2. The difference between mixed venous and arterial PCO2 correlated well to the mixed venous PCO2, implying more efficient pulmonary elimination of PCO2 when the mixed venous PCO2 was high. Pulmonary gas exchange during CPR appears to be independent of alkaline buffer therapy in the form of sodium bicarbonate or tris buffer mixture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632164 TI - A porcine model for sequential assessments of cerebral haemodynamics and metabolism. AB - We present a physiologically stable porcine model designed for sequential assessments of pharmacological effects on mean hemispheric cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) at sustained normocapnia. The dynamic influence of continuously administered fentanyl (0.040 mg.kg-1.h-1 i.v.), nitrous oxide (70%) and pancuronium (0.30 mg.kg-1.h-1 i.v.) on these variables was studied in eight normoventilated pigs. CBF was reliably assessable at 10-min intervals by clearance of intra-arterially injected 133Xe, monitored by an extracranial scintillation detector. CMRO2 was calculated from CBF and the simultaneously measured cerebral arteriovenous difference in blood oxygen content. The intracerebral distribution of a contrast medium injected into the external and internal carotid arteries was studied by angiography, and the cerebral venous outflow was investigated by measurements of the distribution of an intra-arterially administered non-diffusible tracer, [99mTc]pertechnetate, to the internal and external jugular veins. After a 3-h equilibration period, CBF and CMRO2 were determined on six occasions over a study period lasting 1 h 40 min. The mean ranges of these variables were 56-60 and 1.9-2.0 ml.100 g-1.min-1, respectively. We conclude that the model enables repeated assessments of CBF and CMRO2 under stable physiological background conditions and thus valid cerebral pharmacodynamic investigations of drugs given for anaesthesia. PMID- 1632166 TI - Influence of intrathecal morphine and naloxone intervention on postoperative ventilatory regulation in elderly patients. AB - Thirty elderly patients undergoing major hip surgery under spinal analgesia were randomly allocated in a double-blind manner into three groups. The aim was to evaluate the influence of intrathecal morphine and postoperative naloxone infusion on the regulation of ventilation. The Bupivacaine Group received spinal analgesia with 20 mg bupivacaine intrathecally. The Morphine Group received spinal analgesia with 20 mg bupivacaine + 0.3 mg morphine intrathecally. The Naloxone Group received spinal analgesia with 20 mg bupivacaine + 0.3 mg morphine intrathecally + postoperative naloxone infusion intravenously (1 microgram/kg/h over 12 h, 0.25 micrograms/kg/h over the next 12 h). Evaluation of resting ventilation and the ventilatory responses to hypercarbia and hypoxaemia was made on three occasions: before surgery, and 8, and 24 h after the intrathecal injection. Intrathecal morphine had no significant effect on ventilatory regulation in elderly patients undergoing major hip surgery performed under bupivacaine spinal analgesia. Postoperative administration of opioids or sedatives after intrathecal morphine as well as postoperative blood loss associated with a fall in blood pressure appeared to increase the risk of developing respiratory depression. Naloxone infusion seemed to reduce the risk of developing respiratory depression. Furthermore, one third of the elderly had a poor response to hypoxaemia before surgery. PMID- 1632167 TI - Do anticholinergic agents affect the occurrence of postanaesthetic nausea? AB - In order to establish if anticholinergic drugs might influence postoperative nausea and vomiting, 100 ASA I-II adult patients scheduled for minor orthopaedic procedures, varicose vein stripping or inguinal herniorraphy were randomised to receive, in a double-blind fashion, either a premedicant and a reversal dose of 0.003 and 0.0075 mg/kg of glycopyrrolate or 0.006 and 0.015 mg/kg of atropine, respectively. Nitrous oxide, after thiopentone induction was used for anaesthesia with fentanyl and diazepam as supplements and pancuronium for relaxation. In the recovery room, up to 2 h after surgery, 28% of the patients in the glycopyrrolate group and 8% in the atropine group experienced nausea (P = 0.017). Thereafter, the patients complained of nausea at decreased and equal frequencies in both groups. The incidence of vomiting was not statistically significantly different. Droperidol was needed, to control persistent emesis, three times more often in the glycopyrrolate than in the atropine group. It is concluded that substitution of glycopyrrolate for atropine increases the likelihood of postoperative nausea, and continued use of atropine should be considered in patients at risk of postoperative emesis. PMID- 1632168 TI - Evidence against endogenously released adenosine as modulator of the pressor response to hypoxia in isolated rat lungs. AB - Unlike other vascular beds, lung vessels constrict when exposed to hypoxia. However, a marked difference has been noticed as regards the elicitability of hypoxic pulmonary vasoconstriction (HPV) in vivo as compared to in vitro models, like a preparation of isolated rat lungs; in the latter, HPV cannot be evoked from the onset of perfusion, but might be triggered gradually by repeated hypoxic challenges. The formation of adenosine, a potent dilator of most vascular beds, is enhanced during conditions of hypoxia or ischemia. Our hypothesis therefore was that pulmonary vasoconstriction was initially antagonized by tissue-adenosine accumulating during the circulatory arrest necessary for lung isolation, and then, gradually invigorated along with the elimination of adenosine during periods of perfusion with normally oxygenated blood. In a first series of isolated rat lungs, we studied release of adenosine in connection with the third and the sixth hypoxic challenges. Although the vascular responses were of significantly different size, there was no sign of increased adenosine formation during any of the two provocations, as assessed by release of its more stable metabolites hypoxanthine, xanthine and uric acid. In a series of tissue preparations taken at the height of a fully developed hypoxic pressor response and immediately frozen, we could not find significant changes in tissue level of adenosine, hypoxanthine and inosine as compared to controls that had never been exposed to hypoxic challenges. Further, we found no correlation between the size of pressor responses and concentrations of adenosine and its metabolites, in either blood or in lung tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632169 TI - The accuracy of pulse oximetry at two haematocrit levels. AB - The object of this study was to investigate the influence of haematocrit on the accuracy of pulse oximetry. Seven Swedish land race rabbits were studied. The oxygen saturation of haemoglobin was decreased step-wise using increasing fractions of nitrogen to the inspiratory gas. One pulse oximeter probe was attached on the front leg and another probe directly over the common carotid artery. The pulse oximeter readings (SpO2) were compared with simultaneous oxygen saturation analysis (SaO2) by a haemoximeter. The pulse oximeter measurements were performed at the haematocrit levels of approximately 40% and 11%, respectively. We found a good correlation between SpO2 and SaO2 in a wide range of the oxygen saturation, i.e. SaO2 26-100%. After haemodilution the correlation was improved in the range 86-100%, but not in the range 26-85%. No correlation between SpO2 and SaO2 was found when the sensor was attached directly over the artery during normal haematocrit levels. After haemodilution a better correlation was however obtained. These results indicate that the accuracy of pulse oximetry is dependent on the haematocrit level. PMID- 1632170 TI - Central cholinergic action produces antagonism to ketamine anesthesia. AB - Ketamine sometimes produces posthypnotic emergency reactions, such as prolonged hallucination or delirium. In a previous paper, we showed that physostigmine, an anticholinesterase agent, counteracts the manifestation of effects of ketamine at some doses. In the present study, we investigated the mechanism of the antagonistic effect of physostigmine on ketamine anesthesia. At first, rats were given ketamine 75 mg/kg. Immediately after the loss of righting reflex, the four groups of rats were given one of the three central cholinergic agents, physostigmine 0.1 mg/kg, oxotremorine 0.05 mg/kg, 4-aminopyridine 3 mg/kg, or saline as the control. The sleeping times were 10.7 +/- 1.0, 12.3 +/- 0.9, 11.4 +/- 1.3 and 21.2 +/- 0.7 min, respectively. The three cholinergic agents antagonized ketamine anesthesia. In the other groups of rats, the central anticholinergic agent, l-hyoscyamine, 0.5 mg/kg, was given subcutaneously for premedication before the above-mentioned procedure. The sleeping times were 16.3 +/- 1.2 min in the physostigmine group, 18.7 +/- 1.0 min in the oxotremorine group and 18.6 +/- 0.8 min in the 4-aminopyridine group. The sleeping time was significantly longer in the premedicated group than in the non-premedicated group, in the case of the three central cholinergic agents. The sleeping time in the saline group, 20.0 +/- 0.4 min, was not significantly different from that of the control in the non-premedicated case. It is, therefore, considered that the central cholinergic action produces antagonism to ketamine anesthesia. PMID- 1632171 TI - Perioperative complement activation in neonates under halothane or fentanyl anaesthesia. AB - We investigated perioperative changes in complement activation in 18 neonates undergoing elective abdominal surgery with or without thoracotomy by measuring plasma concentrations of C3a and C5a, and leucocyte counts in peripheral blood. The 18 neonates, ranging in age from 1 to 17 days, were randomly divided into two groups according to type of anaesthetic procedures; the "halothane group" consisted of nine neonates in whom general anaesthesia was maintained with halothane and nitrous oxide (N2O) in oxygen, while the "fentanyl group" consisted of nine neonates in whom general anaesthesia was maintained with fentanyl and N2O in oxygen. Plasma C3a and C5a concentrations were higher in the fentanyl group than in the halothane group during the perioperative period. We have demonstrated that abdominal surgical trauma caused complement activation even in neonates undergoing the fentanyl rather than the halothane anaesthesia. Further studies are required to elucidate the precise mechanisms and the clinical implication of perioperative complement activation in neonates. PMID- 1632172 TI - High frequency jet ventilation: use of the Bain system for entrainment. AB - The use of a Bain system to convey anaesthetic gases for entrainment during high frequency jet ventilation (HFJV) was evaluated by examining the effect of varying the fresh gas flow (Vf) on the end-tidal carbon dioxide (PECO2) in 46 ASA physical status I and II patients undergoing extracorporeal shock-wave lithotripsy (ESWL). Anaesthesia was induced with methohexitone (1-2 mg.kg-1), fentanyl (1-1.5 micrograms.kg-1) and vecuronium (0.1 mg.kg-1). After endotracheal intubation with a Mallinckrodt Hi-Lo Jet cuffed endotracheal tube, the patient was immersed in a water bath and HFJV at 150 breaths per minute was instituted with an Acutronic AMS 1000 jet ventilator attached to the side channel of the Hi Lo tube. A Bain system was attached to the proximal end of the endotracheal tube to provide gases for entrainment. Anaesthesia was maintained with an intravenous infusion of methohexitone (5 mg.kg-1.h-1) and 50% nitrous oxide in oxygen for both the jetted and entrained gases. PECO2 was determined at 5-min intervals by a single-breath technique using a calibrated Engstrom Eliza capnograph. Thirty patients were randomly allocated to receive Vf's of 50 (Group 1), 75 (Group 2) and 100 (Group 3) ml.kg-1.min-1, respectively. A further eight patients (Group 4) received a Vf of 100 ml.kg-1.min-1 for 15 min, 75 ml.kg-1.min-1 for the next 15 min and 50 ml.kg-1.min-1 thereafter. In a further group of eight patients (Group 5), Vf was initially 25 ml.kg-1.min-1 for 10 min and was then switched off for the remainder of the procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632173 TI - Ketamine anaesthesia in a patient with septic shock. AB - A 71-year-old male patient was operated on in a septic state (tachycardia, hypotonia, fever peaks, disorientation) because of an occluding tumour of the biliary tract. Ketamine was used as the main anaesthetic. Mean arterial pressure increased markedly and diuresis started during the anaesthesia. The inotropic support (dopamine, dobutamine, noradrenaline) could be reduced. Ketamine anaesthesia seemed to have a beneficial haemodynamic effect in septic shock. PMID- 1632174 TI - Effect of a non-steroidal anti-inflammatory drug, diclofenac, on haemostasis in patients undergoing total hip replacement. AB - Haemostasis was studied in patients receiving diclofenac for postoperative pain relief. Intravenous diclofenac 75 mg over 60 min, followed first by an infusion of 5 mg/h for 15 h and then by 50 mg every 8 h orally was administered to 20 patients undergoing total hip replacement. Eighteen patients receiving a placebo infusion and dextropropoxyfen per os served as controls. The results showed no statistically significant differences between the groups in blood loss, bleeding time (IVY), partial activated thromboplastin time and prothrombin complex assay or in platelet count. The measurements were performed preoperatively, 3 h postoperatively and on the fourth and tenth postoperative days. Plasma concentrations were also determined in ten patients undergoing knee arthroscopy. An i.v. diclofenac infusion of 75 mg over a period of 15 min was administered either once (to half of the patients) or twice. The mean diclofenac concentrations were 28 +/- 5 nmol/ml (+/- s.d.) after 15 min and 36 +/- 12 nmol/ml after the second infusion. The bleeding time in the arthroscopy patients receiving one or two bolus infusions of 75 mg diclofenac remained at the control level. It is concluded that diclofenac given as an intravenous infusion of 75 mg in 60 min, then 5 mg/h for 15 h, followed by 50 mg every 8 h orally, is a safe as dextropropoxyfen for pain relief in patients undergoing major orthopaedic surgery as far as coagulation data are concerned. PMID- 1632175 TI - Combined use of hypothermia and buffering in the treatment of critical respiratory failure. AB - A 20-year-old male, recovering from post-traumatic ARDS, subsequently developed pneumonia with extreme hypercapnia (PaCO2 max 19.4 kPa) and hypoxemia (PaO2 min 5.1 kPa), in spite of maximal mechanical ventilation. Hypothermia was induced by surface cooling, reducing the body temperature from 40 degrees C to a mean of 33.3 degrees C. Buffer infusion (1375 mmol) during the first 2 days increased base excess from 3 to 22 mmol/l and pH from 7.16 to a median value of 7.30. Active cooling was discontinued on day 11. Weaning from the ventilator was possible 9 days later and the patient subsequently recovered fully. Combined use of hypothermia and buffering might offer an alternative to extracorporeal lung assist (ECLA) and facilitate a reduction of barotrauma and oxygen toxicity during mechanical ventilation. PMID- 1632176 TI - Interscalene plexus block for arthroscopy of the humero-scapular joint. AB - Interscalene plexus block was performed in nine patients subjected to shoulder arthroscopy. The operating conditions, including muscle relaxation, were fully adequate in all patients (after additional local anaesthesia of the skin in four patients). With the exception of one patient who experienced temporary hoarseness (probably due to a concomitant block of the recurrent laryngeal nerve), no side effects were found and the patients tolerated the surgical procedure well. Interscalene block might be a suitable alternative to general anaesthesia for shoulder arthroscopy. However, additional local anaesthesia at the site where the arthroscope is to be inserted is frequently required. PMID- 1632177 TI - Comparison of nicardipine and sodium nitroprusside in the treatment of hypertension after coronary bypass surgery (a pilot study). AB - Sodium nitroprusside is widely used in the treatment of hypertension after coronary artery bypass surgery despite its toxicity and its deleterious effect on the coronary circulation. The aim of this study was to compare the safety and effectiveness of nicardipine with sodium nitroprusside in a randomized study. Nicardipine and sodium nitroprusside are effective for controlling hypertension after coronary artery surgery. Oxygen myocardial balance was more often improved by nicardipine than by sodium nitroprusside. Hemodynamic stability was better with nicardipine which was also devoid of toxicity and might therefore have advantages over sodium nitroprusside in the management of hypertension after coronary artery surgery. PMID- 1632178 TI - Unusual complication after pelvic surgery: unilateral lower limb crush syndrome and bilateral common peroneal nerve paralysis. AB - We present a patient who developed a right anterior leg compartment syndrome and bilateral common peroneal nerve paralysis following radical hysterectomy in the lithotomy position. We describe the physiopathology of the syndrome, its various etiologies, the treatment, and prevention of this complication. PMID- 1632179 TI - Intraocular pressure changes in response to endotracheal intubation facilitated by atracurium or succinylcholine with or without lidocaine. AB - Changes in intraocular pressure (IOP) and hemodynamics (SP, DP and HR) were measured in 105 patients ASA I and II randomly assigned into seven equal and comparable groups (A to G) during induction of anesthesia and endotracheal intubation facilitated either by succinylcholine or atracurium with or without lidocaine. IOP decreased significantly (p less than 0.01) after induction of anesthesia with thiopentone in all the groups. While atracurium with or without lidocaine did not affect IOP following complete suppression of train-of-four (groups A, B, and C), succinylcholine per se or in combination with lidocaine (groups F and G) significantly (p less than 0.01) increased IOP after induction with thiopentone but not exceeding the baseline IOP level. IOP was significantly elevated (p less than 0.01) immediately after endotracheal intubation in all the groups when compared to IOP following thiopentone administration. In those patients given atracurium (groups A to E), IOP increased (p less than 0.05) in response to endotracheal intubation above the baseline level only in group B where atracurium was divided into a priming and intubating doses. However, the priming dose did not have any significant effect on the onset time of complete twitch suppression of train-of-four and did not affect the intubation conditions compared with the uniformly excellent conditions found with atracurium over an equivalent bolus dose of the relaxant. In patients who received succinylcholine only (group F), IOP immediately after endotracheal intubation was significantly greater (p less than 0.01) as compared to the baseline and did not return to the baseline level until 3 minutes after endotracheal intubation. The use of lidocaine in combination with atracurium (group D) or succinylcholine (group G) for a rapid sequence intubation did not affect IOP following endotracheal intubation. However, atracurium when used in a rapid sequence intubation could not produce similar intubation conditions when compared with succinylcholine. Consequently, we cannot endorse atracurium as an alternative to succinylcholine for patients with penetrated eye injuries and full stomach requiring rapid sequence intubations. In this context, the role of IV lidocaine in mitigating or preventing the systemic and ocular reactions and especially the acute increase in IOP associated with endotracheal intubation should be emphasized. PMID- 1632180 TI - The inferior conjunctiva of the monkey. AB - Light- and electron-microscopical techniques were used to study the structure of the inferior conjunctiva of monkeys including the third eyelid (nictitating membrane). The cell layers of the conjunctival epithelium were 8-10 at the margin, 6-8 near the limbus and 2-4 in other areas except in the third eyelid where there were 1-4 layers. The epithelium was 90-100 microns thick at the margin and 35-40 microns at the other areas except at the third eyelid where it was 10-45 microns thick; near the limbus it was 55-60 microns thick. The morphological differences between the epithelia of the various areas of the inferior conjunctiva are highlighted. The similarities and differences between the human and monkey inferior conjunctivas are discussed. PMID- 1632181 TI - Gross (mesoscopic) and applied anatomy of the anterior inferior cerebellar artery in man with special reference to its course through the cerebellopontine angle region. AB - In the present paper, we describe anatomical variants of the anterior inferior cerebellar artery in man for applicative purposes. Our goal was to provide the surgeon with a detailed anatomical view of the region. This is similar to what he may observe through the surgical microscope using modern microsurgical techniques. We have focused our attention on the segments of the artery comprising its origin, its course until it reaches the cerebellum and its main collateral branches. Our results confirm the great variability of the elements under study, but enable the establishment of a few basic variational patterns. These patterns together with their relative frequency may be helpful in microsurgery. PMID- 1632182 TI - Pancreatic microcirculation in the common tree shrew (Tupaia glis) as revealed by scanning electron microscopy of vascular corrosion casts. AB - Pancreatic vascular casts of the common tree shrew (Tupaia glis) were prepared by infusion of Batson's No. 17 plastic mixture into the blood vessels and examined by scanning electron microscopy (SEM). Routine histological study of the pancreas was also performed. It was found that the A and D cells appeared to occupy the core whereas the B cells were found at the periphery of the islets of Langerhans. With SEM, the insular arteriole, a branch of the interlobular artery, was shown to penetrate deeply into the core of the islets before branching off into the glomerular capillary network supplying the islets. These capillaries reunited at the periphery of the islets to become vasa efferentia and then gave off capillaries to anastomose with those in the exocrine part of the pancreas, the insuloacinar portal system. Such an insuloacinar portal system found in the pancreas of the tree shrew was similar to that found in the horse and monkey. However, there were some intralobular arterioles which did not end in the islets but directly branched into the interacinar capillary network and periductular plexus. The capillaries in the exocrine part not only gathered into intralobular venules which confluently formed the interlobular vein but also supplied the duct system. The periductular plexus also collected blood into the intralobular venule and interlobular vein, respectively. PMID- 1632183 TI - Timing and sequence of the events in the development of extraocular muscles in staged human embryos: ultrastructural and histochemical study. AB - The ultrastructure and the appearance of glycogen were studied in the extraocular muscles of 14 externally normal human embryos (Carnegie stages 13-21). At stage 16, myofibrils with an immature Z line and glycogen granules appeared in the cytoplasm of the myoblast. The myoblasts came into cluster at stage 18, and fusion between the myotubes was observed at stage 20. At this stage, an M line appeared in the myofibrils. At stage 21, an A band with a Z line and an H band with an M line were observed, the sarcoplasmic reticulum appeared in the cytoplasm of the muscle fibers and glycogen increased in volume in the cytoplasm. In the previous study, we showed that the muscle-specific isoenzymes, such as creatine kinase, beta-enolase and glycogen phosphorylase, appeared from stage 18 to 20 in the extraocular muscles. The previous findings and the present results suggest that the fusion of the muscle cells occurs in the period when some molecular markers of muscle differentiation are expressed in vivo. PMID- 1632184 TI - [Functional cytology of the apocrine glands of the anal sac in cats, Felis silvestris f. catus]. AB - Apocrine glands of the anal sacs in cats (Felis silvestris f. catus) were examined by transmission and scanning electron microscopy. The secretory cells exhibit a typical equipment with organelles that varied according to the season as well as the animal's sex and state of reproduction. This can be mainly explained by seasonal differences in secretory activity. The cytological dynamics observed are, particularly, related to the smooth endoplasmic reticulum, which, for the first time, can be demonstrated in its crystalloid form in apocrine glands. PMID- 1632185 TI - Analysis of the tendinous structure in human masticatory muscles. AB - In the masticatory muscles, the development of bundles of the tendon was examined: they were composed of many collagen fibers and a few elastic fibers. In the masseter muscle, the property of the tendon differs in the distribution and size of collagen fibers and elastic fibers in comparison with those of other masticatory muscles. This difference is concerned with the kinetic force for the stress or the stretch of each tendon and muscle during jaw movement. PMID- 1632186 TI - Autonomic innervation of the salivary glands in cebid monkeys: a histochemical study. AB - The autonomic innervation of the major and minor salivary glands was studied in five species of cebid monkeys using acetylcholinesterase (AChE) and catecholamine histochemistry. Catecholamine-containing and AChE-positive nerve fibres were observed in the vessels and secretory endpieces of all glands, with no apparent predominance of one type over the other. In the intralobular ducts, however, the cholinergic innervation predominates. In the major salivary and minor sublingual glands the density of the nervous supply was higher, whereas in the secondary mandibular and posterior lingual glands it was less dense. The morphological patterns of salivary gland innervation found in Cebidae are compared with those of the related family Callitrichidae. PMID- 1632187 TI - Prothymosin alpha expression in lymph nodes and tonsils: an optical and ultrastructural study. AB - Prothymosin alpha (ProT alpha) distribution in human and rat lymph nodes and human tonsils was studied by means of immunohistochemical methods, using specific antibodies raised against thymosin alpha 1. We observed ProT alpha immunoreactivity in lymphoid cells of the germinal centers both in humans and rats. In human tonsils, positive cells were also seen in the basal layer of the surface epithelium. These results support the hypothesis that ProT alpha expression is restricted to actively proliferating cells. Immunoelectron microscopy revealed that ProT alpha was located in the nucleus, mainly in the border between euchromatin and heterochromatin. PMID- 1632188 TI - Effects of short-term treatment with calcium on the parathyroid glands in golden hamsters of different ages, with special reference to large vacuolar bodies. AB - The effects of different ages on large vacuolar bodies in the parathyroid glands of golden hamsters after short-term treatment with calcium were investigated. In the parathyroid glands of the young and adult animals 15 min and the senile animals 15 and 60 min after administration of calcium, the percent area occupied by large vacuolar bodies was significantly increased as compared to that of the young, adult and senile control animals, respectively. These findings suggest that the percent area occupied by large vacuolar bodies is increased in response to acute hypercalcemia. It is thought that in the parathyroid glands suppressed by hypercalcemia there is a relationship between the percent area occupied by large vacuolar bodies and aging. PMID- 1632189 TI - Unilateral immobilization affects contralateral rat gastrocnemius muscle architecture. AB - In order to study the effects of unilateral short length immobilization on the contralateral gastrocnemius muscle (GM), length measurements were conducted on photographs taken in the active condition (tetanic plateau). Comparison of geometry of experimental and control muscles was made at optimum muscle length. The results show that a process occurred in the muscle which can be ascribed predominantly in terms of atrophy. This atrophy did not reach a maximum after 4 weeks but gradually increased in time. The altered conditions imposed on the muscle changed its architecture. It was shown that variables of the contralateral GM muscle are not representative of those of normally used muscles and should therefore not be used as control muscles for the determination of immobilization effects. PMID- 1632190 TI - Neural differentiation as an expression of UV sensitivity of melanocytes. AB - The present work is to study neural differentiation in melanocytes in relation to the cell cycle and UV exposure. Whole skin organ cultures of vitiliginous skin were exposed to a pulse of UV with and without prior Adriamycin treatment. It was observed that the highly dendritic marginal melanocytes are destroyed on UV exposure during the depigmentation phase but not during repigmentation. The melanocytes are resistant to UV destruction during the G2 phase as seen on Adriamycin treatment. They show a prominent increase in dendricity as well as biphasic activity to produce increased melanin and noradrenaline. Thus, the melanocytes form a UV-sensitive neural network in the skin. These responses are reminiscent of the repigmentation and depigmentation of coat color in animals exposed to extreme variations in the day/night cycles as seen at the poles. PMID- 1632191 TI - Sexually dimorphic duct system of the submandibular gland in mouse with testicular feminization mutation (Tfm/Y). AB - The X-linked testicular feminization mutation (Tfm/Y) in the mouse is characterized by androgen insensitivity of the target cells. The aim of this study was to examine sexually dimorphic development of the submandibular gland of Tfm/Y mutant mice in comparison with those of wild-type male, wild-type female and heterozygous Tfm female mice. In either 30- or 90-day-old wild-type male mice, the granular convoluted tubules (GCT) of the glands were more developed, and the relative occupied areas (ROA) of GCT were superior to those of the age matched wild-type and heterozygous Tfm females. In androgen-insensitive Tfm/Y mice, the glandular structures rather resembled the female glands, showing lower values of the ROA of the GCT. Sex differences in the mitotic rate were observed at 30 days of age, being significantly higher in the wild-type male GCT than in the female GCT. Thereafter, the mitotic rate of the wild-type male GCT declined to the female levels by 90 days of age. The mitotic rate of GCT in Tfm/Y mutants was as low as those of the females during observation periods. An other three regions, the acini, the intercalated ducts and the excretory striated ducts, were not significantly different in either the ROA or the mitotic rate among wild-type males and females, and Tfm/Y. On the other hand, either the ROA or the mitotic activity of GCT of the glands in Tfm/Y mutants was completely unaffected by 5 alpha-dihydrotestosterone (DHT).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632192 TI - SEM study on the dorsal lingual surface of the common tree shrew, Tupaia glis. AB - The dorsal lingual surface of the common tree shrew was examined by SEM after treating it with HCl to remove the mucous substance. Filiform (FI), fungiform (FU) and circumvallate papillae (CI) were observed. The FI exhibited a small circular bulge surrounded by anterior and posterior filamentous processes. FU were scattered among the FI. There were 3 CI separating the anterior 4/5 from the posterior 1/5 of the tongue. In addition, a group of conical projections with caudal orientation was found anterior to the palatoglossal fold on each side of the tongue. Microridges were widely observed on the entire dorsal lingual surface, except on the free surface of FI processes. PMID- 1632193 TI - Histochemical localization of carbonic anhydrase in the testis and epididymis of the rabbit. AB - The distribution of carbonic anhydrase (CA) was studied in the testis and epididymis of mature, male rabbits using a cobalt precipitation method. CA was found only in the endothelium of the capillaries in the testis. The epididymal duct was divided into initial, middle and terminal segments. Strong cytoplasmic CA was present in the apical cells in the initial and middle segments. Vacuoles with CA staining in the membranes were found in the principal cells in the middle segment. Intensely stained basal cells were present in the terminal segment. In the last part of the terminal segment and the first of the ductus deferens the basolateral cell membranes were also stained. The function of the enzyme is discussed especially in relation to acidification of the epididymal fluid and facilitation of CO2 diffusion. PMID- 1632194 TI - Effect of microbial immunomodulants on the course of LCMV infection in old mice with thymus involution. AB - Old mice with thymus involution were treated intraperitoneally with a live vaccine containing a mesogenic strain of attenuated Newcastle Disease Virus or with Mannozym (M, 1% zymosan suspension). One day after the treatments mice were infected with lymphocytic choriomeningitis virus (LCMV) intracerebrally. The fatal course of the consequent LCMV infection was stimulated by each of the pretreatments, indicating that the cellular immune response was stimulated. The results are compared with results of experiments carried out on suckling, young adult and old mice in similar experimental systems. The authors' previous publication suggesting that the direction and degree of the immunomodulant effect may be influenced by the actual age-dependent condition of the lymphoid system, have been confirmed. PMID- 1632195 TI - Morphological changes of Neisseria gonorrhoeae in amniotic fluid of pregnant women in their midtrimester. AB - Ten selected samples of amniotic fluid obtained through transabdominal amniocentesis from 10 pregnant women in their 17th-19th weeks of pregnancy were investigated for the survival of Neisseria gonorrhoeae in amniotic fluid. In 8 cases an antibacterial effect was observed with morphological changes comparable to the effect of benzylpenicillin. When N. gonorrhoeae was inoculated in amniotic fluid at 10(5)-10(7) cells/ml, it survived as an average 2 h longer than after inoculation of 10(2)-10(4) cells/ml. Electron microscopic pictures of gonococci taken after 2.6 and 24 h incubation in amniotic fluid correlated with the growth curves. Electron microscopically there were marked morphologic changes of N. gonorrhoeae, viz. vacuolar degeneration of their cytoplasm with a damage to the bacterial wall up to its complete destruction and lysis of the cell. PMID- 1632196 TI - Effect of Mannozym on the course of LCMV infection in mice with undeveloped and normal immune system. AB - Adult germfree (Gf) mice with undeveloped immune system due to antigen deficient environment, conventional (Cv) mice with normal immune system and Cv suckling mice with undeveloped immune system due to age were treated intraperitoneally with Mannozym (M, 0.1% zymosan suspension) 4 days or 4 days and 1 day before the intracerebral inoculation with lymphocytic choriomeningitis virus (LCMV). One dose of M was equal to 40 mg/kg of zymosan. In suckling mice, both applied doses of M contributed the development of fatal lymphocytic choriomeningitis after infection with 100 LD50 dose of LCMV, thus M pretreatment increased the cellular immune response to LCMV infection. M pretreatments had no influence on the course of LCMV infection either in adult Gf or in Cv mice. Spleen hypertrophy was caused by applied doses of M both in adult (Gf and Cv) and Cv suckling mice, but modulating effect on the cellular immune response manifested simultaneously only in Cv sucklings. PMID- 1632197 TI - Epidemiological and microbiological data on Salmonella enteritidis. AB - The number of Salmonella enteritidis isolations started to rise in humans, eggs and egg products in 4 territories out of the examined 9 territories of Russia in 1986. The spread of S. enteritidis infections was connected with the consumption of hen's eggs as it was demonstrated by the analysis of the local outbreaks. Phage type of 1142 S. enteritidis strains isolated in Russia was determined using the Hungarian typing scheme. The strains were typable in 95.3% and 12 phage types were found. Phage type 1 was the most frequent (86.7%) among human strains and also among strains originated from hen and egg products. The examined 18226 human S. enteritidis strains isolated in Hungary between 1984 and 1989 belonged to 24 phage types and phage type 1 was predominant, the incidence of this type varying between 69.3% and 93.2%. The strains were sensitive to antibiotics, multiresistant strains were found in 1%. Plasmid content was examined of 138 strains; a 38 Md plasmid was carried by all of them and a 96 Md plasmid was harboured by 11 antibiotic-resistant strains. The tested strains produced enterobactin but no aerobactin. PMID- 1632198 TI - Shigella-type pathomechanism in the "mouse model". AB - A strain of Escherichia coli K-12 carrying the 140-Megadalton virulence plasmid of the enteroinvasive E. coli--J53(pSPl)--showed high virulence in the "mouse model", in chick embryos, but not in the Sereny test. It expresses the outer membrane proteins thermoregulatedly, encoded also by the virulence plasmid. In orally infected streptomycin-pretreated mice this strain infects only the large bowel, shows adherence to the epithelial surface, but in its first step preferentially to the mucus excreted by the goblet cells. Epithelial penetration and intracellular multiplication occurs with a characteristic localization of bacteria in the depth of crypts. Consequence of the infection is degeneration of the epithelial surface, its denudation. PMID- 1632199 TI - Detection of Legionella pneumophila-specific antibody by indirect immunofluorescence assay. AB - Antibodies to Legionella pneumophila were found by indirect immunofluorescence assay in 525 samples of human serum. The samples were obtained from 451 patients who were suspected of having an acute infectious illness, with mainly respiratory symptoms; 90 patients had antibodies to L. pneumophila (19.9%). The results suggest that the prevalence of L. pneumophila is greater than had previously been supposed. PMID- 1632200 TI - Mixed cultivation of Trichoderma reesei and Aspergillus ochraceus for improved cellulase production. AB - Aspergillus ochraceus IMI 317911 was screened to be a high cellobiase producing strain (2.40 IU/ml). The mixed batch cultivation of Trichoderma reesei QM 9414/Rut C-30 and A. ochraceus IMI 317911 resulted in a balanced enzyme as compared to singly grown cultures. The milled rice straw (6%, w/v) as carbon source was found suitable for production of cellulases resulting in a Filter Paper Activity (FPA) of 1.83 IU/ml and a cellobiase production of 1.63 IU/ml after 7 days of stirred cultivation. An overall cellulase productivity of 10.89 IU/l/h and an enzyme ratio to cellobiase of 1.12 was achieved. PMID- 1632201 TI - Differences and similarities in the sensitivity of lymphocytic and macrophage plasma membrane to deoxycholate. AB - Human tonsillar lymphocytes separated on nylon wool and rat macrophages showed different sensitivity to deoxycholate (DOC) treatment at a low (0.24 mM, 0.01%) concentration for 3 h. The T cell-enriched fraction was stimulated more readily by PHA whereas the B-cell enriched fraction lost its adherence and a decrease of chromium binding capacity was observed after the detergent treatment. Rat peritoneal macrophages under the same conditions lost their chromium label and lysozyme content, whereas their adherence and phagocytic capacity decreased dramatically without affecting their binding capacity. Higher sensitivity to the detergent was observed in peritoneal macrophages compared to tonsillar lymphocytes when various DOC concentrations were used. These findings proved that this low concentration DOC treatment, at least in macrophages, touched mainly the adhesive proteins and the dynamics of the membrane and not its receptor associated properties. PMID- 1632202 TI - Plasmids encoding for erythromycin ribosomal methylase of Staphylococcus epidermidis and Staphylococcus simulans. AB - Two 1.7 Md plasmids of Staphylococcus epidermidis and three ones of Staphylococcus simulans determining inducible macrolide-lincosamide resistance are identical as judged by restriction endonuclease fingerprinting. These plasmids designated pEI2101, pEI9105, pE1107, pEI1108 and pEI6104, respectively, belong to the incompatibility group 12. Dot-blot hybridization by photobiotin labelled gene probe developed from S. aureus erythromycin ribosomal methylase gene showed cross hybridization between methylase-coding reference plasmids and the tested ones. The examined plasmids proved to be no transmissible in mating experiments into S. aureus recipients. PMID- 1632203 TI - Plasmids determining enzymatic inactivation of lincomycin in Staphylococcus epidermidis. A preliminary report. AB - Coagulase-negative staphylococcal strains isolated from immunocompromised patients harboured in 41% non-MLS type lincomycin resistance determinant. Two kinds of resistance plasmids were detected in Staphylococcus epidermidis isolates of this origin in connection with lincomycin resistance. One of them represented by pBI1 and pBI84 (1.4 Md in size) determines no other resistance marker. The pBI109PGL plasmid determines also penicillinase production and aminoglycoside resistance, its molecular mass is 31 Md. Hybridization using linA, linA' and linA like specific gene probes suggested occurrence of genes of lincosamid inactivating enzyme belonging to the lin gene family but differring from the previously characterized determinants. PMID- 1632204 TI - Chronic facial pain together with severe depression is responsive to electroconvulsive therapy. A case report. AB - Electroconvulsive therapy (ECT) is widely accepted as a treatment for severe depression, but is seldom used in the treatment of chronic pain even though chronic pain and depression frequently occur together. This study presents a case in which ECT relieved both severe depression and chronic pain. It seems that the recognition of depressive disorders merits more attention and that ECT as a treatment for chronic pain in patients with severe depression should be taken into consideration in cases in which other treatments have failed. PMID- 1632205 TI - Explanatory models for total edentulousness, presence of removable dentures, and complete dental arches in a Swedish population. AB - On the basis of data from a questionnaire study of 3000 inhabitants of Orebro County, Sweden, aged 45-69 years, the relative importance of various socioeconomic factors for dental conditions were analyzed in stepwise logistic regression models. Two different patterns were found: one in relation to the best dental condition (complete dental arches), another in relation to the poorest conditions (total edentulousness and presence of removable dentures). Next to age, education and income showed the highest predictive values in relation to the presence of removable dentures and total edentulousness. Place of residence and gender seemed to be of less importance than earlier. In relation to complete dental arches, there were lower values for most variables. One of only four significant variables was the attitude variable 'importance of good dental appearance'. The results may indicate the development of a new pattern of influences on dental conditions, mainly based on education and attitudes. PMID- 1632206 TI - Design of a socio-ecologic caries model and testing on 50-year-old citizens of Oslo, Norway. AB - The purpose of the present study was to design a socio-ecologic caries model based on a general health model and to test the fit of data collected from a random sample of 200 50-year-old Oslo citizens to this designed model. The intention was also to investigate the relative importance of the four items environmental, behavioral, human biology, and health care organization factors. The dependent variable, number of carious surfaces, was recorded clinically and radiologically. The mean number of carious surfaces was 3.0 (SD, 3.5), with a range from 0 to 17, and the four items explained 5%, 25%, 28%, and 13% of the variance in number of carious surfaces, respectively. The complete model explained 42%, whereas traditionally used variables on the basis of the Keyes triad explained only 22% of the variance. The findings from the present study indicate that dental caries is a multifactorial disease with both behavioral and biologic determinants, and the socio-ecologic caries model represents a relevant supplement to the Keyes triad. PMID- 1632207 TI - The predominant microflora of the palatal mucosa in an elderly island population. AB - The prevalence and microbiology of macrophotographically documented denture stomatitis were studied in denture wearers participating in an interdisciplinary health-monitoring project (Koster Health Project) on the Koster islands, Sweden. Upper dentures were used by 26.6% of the adult population, and 59.2% of the denture wearers had stomatitis. Denture stomatitis type I was identified as sialadenitis. The more severe forms of denture stomatitis (types II and III) demonstrated increased recovery of microorganisms in the palatal mucosa in addition to sialadenitis. Only one proband showed increased growth of fungi. Hemophilus spp. and Bacteroides spp. were the predominating microorganisms in stomatitis types II and III. Shifts in the normal oral flora are suggested to be an important factor for the development of denture stomatitis. It is concluded that bacterial colonization on the palatal mucosa may play an important role in denture stomatitis in this relatively healthy population. PMID- 1632208 TI - A clinical examination of ceramic (Cerec) inlays. AB - Two hundred and five Cerec ceramic inlays placed by 8 dentists in 72 patients were examined independently by 3 calibrated evaluators 12-24 months after insertion, using the criteria of the California Dental Association (CDA) and also certain periodontal variables. Proximal dental plaque and bleeding on probing were not seen more often on Cerec surfaces than on control homologous surfaces. Ten patients reported postoperative sensitivity after treatment with Cerec inlays. Excellent CDA ratings for Color and Surface were obtained in 57% and 26%, respectively, and for Anatomic Form and Margin Integrity in 55% and 83%, respectively. Obvious differences were seen among the participating dentists with regard to the clinical quality of Cerec inlays. At present, the long-term performance of the Cerec technique cannot be predicted. PMID- 1632209 TI - The clinical performance of two groups of functioning class-II cast gold inlays. AB - The length of service and the clinical performance of two groups of functioning class-II cast gold inlays in patients attending a private practice were assessed by conventional clinical and radiographic examination. In one group all inlays were older than 25 years (median age, 34 years), and they had an extended outline form. The impression technique was based on a thermoplastic material in a copper ring. In the other group, comprising inlays inserted during the past 25 years (median age, 16.5 years), the outline form was minimal and an elastic impression material in a copper ring was used. The inlays in the older group appeared to perform better than those in the younger group. In both groups recurrent caries appeared to be the predominant reason for repair. PMID- 1632210 TI - [The intact, injured and repaired knee: in-vitro experimental biomechanics and level walking]. AB - In vitro simulation of knee joint movement during walking on flat ground was developed in this experimental study. Such movements are of interest for surgical and rehabilitation medicine in order to improve knowledge in the field of dynamic behavior of the knee joint during the entire range of motion: spatial kinematics and strains and stresses on the different components, in the case of intact knee, as well as of the operated one. As internal strains and stresses could not be measured directly, the aim of this experimental study was also to simulate such factors in a model using experimental input data. A simulator of joint flexion was built: it was composed of a hydraulic universal testing machine which allowed the main flexion-extension of the knee joint and an additional hydraulic device to impose the quadriceps extension force which represented the muscular action, synchronized with the imposed flexion-extension. The anatomical automatic passive rotation and valgus-varus motion were freely allowed, and these were measured during joint motion. In addition the lateral ligaments were fitted with strain sensors in order to measure their time-dependent behavior. The imposed flexion motion and quadriceps force were also measured to verify that they were accurately synchronized. The time-dependent values of force and flexion were taken from the literature. The analysis gave the mean result of eight reliable knee joint determinations: first of all intact, then after removing the anteroexternal cruciate ligaments, and finally after joint replacement by total knee prosthesis. One main conclusion was the comparison between automatic rotations, which decreased significantly after prosthesis surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632211 TI - Ultrasound in the diagnosis of the early stages of hemophilic arthropathy of the knee. AB - We have studied the knees of 50 patients with hemophilia A, using ultrasound (US) when conventional radiology did not detect any secondary osseous changes. The sonographic images were compared with those obtained from 50 healthy controls. The mean age of this series was 14.6 years. Our results suggest that sonography as a diagnostic technique in the initial stages of hemophilia permits differentiation between suprapatellar effusion and synovial thickening. It also reveals early cartilaginous involvement. PMID- 1632212 TI - The validity and reliability of measurements in spinal deformities: a critical appraisal. AB - Quantitative measurement of spinal deformity is the preliminary step in order to plan a therapeutic regimen. The most commonly used methods and, for this matter, practically any measurement methods, may have several sources of errors, namely: a. errors in taking a radiograph; b. errors intrinsic to the measurement method; c. errors due to anatomical deformity of the vertebrae; d. observer errors in measurement technique. These are discussed, and suggestions are given to minimize them. PMID- 1632213 TI - [Bone anchorage and surface condition of the implant. Validity of extraction tests]. AB - The mechanical strength of the bone-implant interface depends on the morphology and the composition of the implant surface. The great variety of coating materials as well as the condition of the surfaces to be covered, makes a comparative and preclinical evaluation of the different materials for prostheses necessary. The results, the validity and the limits of the extraction tests are discussed in this article. PMID- 1632214 TI - [Spatial kinematics of the femoro-tibial articulation of the human knee: experimental characterization and surgical implication]. AB - The entire flexion of the human knee joint was experimentally studied by means of spatial solid kinematic theory. This study used postmortem joints, initially intact, then with the menisci removed, and finally without the antero-external cruciate ligament. The instantaneous velocities were defined in kinematic theory; then they were transformed into incremental displacements of the tibia which was considered as a moving solid relative to the femur, which was considered as the reference solid. The rotational movement of tibia was computed as being the main degree of freedom; then it was divided into three physiological components: flexion-extension, axial rotation, and varus-valgus rotation. The computation of the instant axis of the motion allowed definition of an area that was characterized as a central zone of the joint motion. This 3-dimensional approach was in opposition to the classical but incorrect definitions of the instant center of rotation, which can be described only for movement within a plane. Eight anatomical knee joints were tested and their mean results were used to elucidate conceptual problems relative to the femoro-tibial knee-joint prosthesis design. PMID- 1632215 TI - [Complex injuries of the proximal humerus treated with humeral head prosthesis. Apropos of 21 cases reviewed after a median 4-year follow-up]. AB - Of a total of 35 complex fractures of the upper humeral epiphysis treated by Neer arthroplasty, 21 were evaluated at a mean of 4 years after operation. The shoulder function according to Constant was 70% of the contralateral one. The internal and external rotations were rarely symmetric. Clinical improvement was possible during the first 2 years. Late breakage and migration of wires used to fix the tuberosities caused failure of this method of fixation. Dynamic radiographs revealed significant gleno-arthroplastic movement and a constant medialization of the prosthetic humerus. PMID- 1632216 TI - [Intramedullary nailing osteosynthesis with epiphyseal fixation of fractures of the proximal humerus in adults. 1 to 3-year follow-up]. AB - The authors used a medullary pinning with epiphyseal fixation in the treatment of superior metaphyseal fractures of the humerus for 41 patients aged 22 to 82 years. There were 28 cases with epiphyseal fractures and 12 with metaphyseal fractures. The follow-up was 1 to 3 years. The pins were introduced through the triceps brachii after perforation of the diaphysis, 1 cm above the ulnar fossa. Results were very good. Strength returned within 8.5 weeks. There was only one case of nonunion of a proximal diaphyseal fracture due to a technical fault (diastasis between fragments). Rehabilitation began immediately, resulting in good elbow motion in 35 cases. The shoulder motion was the same as the healthy side in 36 cases, and inferior to 90 degrees of abduction in only two complex epiphyseal fracture. The proximal humerus was never perforated by the pins. The authors find this new instrumentation to be very effective. PMID- 1632217 TI - [Post-traumatic cubitus varus in children (apropos of 8 cases in African children)]. AB - The author describes his experience after treatment of 8 cases of cubitus varus secondary to displaced supracondylar fractures of the humerus in African children. Measurement of the Baumann angle is necessary for the assessment of cubitus varus. The median angle is 24 degrees with a range of 10 degrees to 45 degrees. Indications were dictated by functional problems, discomfort, and esthetic considerations. The surgical treatment consisted in a supracondylar osteotomy of the humerus for correction of cubitus varus. PMID- 1632218 TI - Inter- and intratester reliability of radiographic measurements of spondylolisthesis. AB - Thirteen radiographic methods to measure spondylolisthesis were assessed to determine: 1. whether or not the different methods were correlated with each other; 2. their precision in detecting vertebral displacements; 3. inter- and intra-measurer reliability among six orthopedic surgeons performing radiographic measurements. Several methods were found to be correlated with each other in detecting spondylolisthesis on radiographs. However, on simulated displacements only three of them showed good correlation (r greater than or equal to 0.95, p less than 0.01). Intra- and intergroup correlations among the orthopedic surgeons were equally good (r greater than 0.90; p less than 0.01). PMID- 1632219 TI - [Experimental carpal displacement induced by bony lesions]. AB - Bony lesions were created experimentally in 48 fresh cadaver wrists. They consisted of radial and scaphoid resections along the extent of the proximal carpal row, representative of clinically-induced (usually traumatic) lesions. The displacements obtained experimentally to mirror each clinical situation modify the physiologic equilibrium established between the trans-osseous forces and the ligaments. The comparison between the experimentally-induced lesions and clinical displacements shows the etiology of the clinical conditions which indicates the proper treatment. PMID- 1632220 TI - Incidence of neonatal hip instability: are there seasonal variations? AB - We wanted to establish whether the season of birth affected the incidence of neonatally diagnosable hip instability in Eastern England. Data relating the numbers of maternities to the numbers of cases of congenital displacement of the hip diagnosed in neonates were analyzed month by month over a period of 8 years. The study covered 185,744 maternities and 154 cases of displaced hips during the period 1979-1986. While there were wide fluctuations in the monthly incidence, there was a striking excess of the malformation in late winter and early spring, i.e. in January, February, March and April, and a progressive decline in the succeeding months. The cause or causes of the seasonal variation are unknown. PMID- 1632221 TI - [Villonodular synovitis of the shoulder. Apropos of a case report]. AB - The authors report a case of villonodular synovitis of the shoulder, treated by synovectomy. The diagnostic problems, treatment and results are reviewed. PMID- 1632222 TI - Chondromyxoid fibroma in the metacarpal bone of the thumb. AB - We present a case of a chondromyxoid fibroma in the exceptionally rare location of the first metacarpal bone in a 12-year-old boy. The tumor had evolved asymptomatically over a period of 8 years destroying all diaphyseal trabecular bone. No recurrence was evident 50 months following aggressive curettage of the metacarpal lesion, which presented a predominantly myxoid appearance. PMID- 1632223 TI - [Intraneural fibrolipoma of the median nerve at the thumb. Apropos of a case and literature review]. AB - The authors report the case of a rare tumor of the median nerve in a 67-year-old man. They provide a review of the literature, and discuss the original macroscopic and histologic characteristics, the etiological hypotheses and the possibilities of treatment of this tumor. PMID- 1632224 TI - Kashin-Beck's disease. AB - A case of Kashin-Beck's disease is presented. It is an acquired, disabling, polyarthritic, degenerative condition of early onset, sometimes leading to a variable degree of dwarfism. It occurs endemically in certain Asian areas. Treatment is, if possible, preventive. In the established disease the therapy is that of any other form of secondary osteoarthritis. Reconstructive surgery and removal of loose bodies may be needed in severe cases (11). Early detection, facilitated by careful family history taking, is a prime requisite, especially in non-endemic areas (7). PMID- 1632225 TI - [Osteoid osteoma of the femoral neck in children: diagnostic problems]. AB - The authors report a case of an osteoid osteoma of the femoral neck in a child, aged 3 1/2. This is a benign bone tumor, frequently painful with variable relief obtained with salicylates. Clinical latency is not exceptional in children, owing to the delayed diagnosis. When located in the femoral neck it is usually discovered after a delay, owing to the misleading clinical signs and the frequently normal standard x rays. The only treatment for cure is the excision of the nidus, which is usually difficult because of the anatomical location and the perioperative adjustment. PMID- 1632226 TI - [Prevention of peridural fibrosis following laminectomy. Apropos of a case of monoradicular paralysis due to an intracanalar hematoma on Gelfoam]. AB - Gelfoam has routinely been used, according to Larroca and Macnab, to prevent scar formation about the dura mater and the nerve roots after laminectomy. We report a case in which postoperative monoradicular paralysis resulted from compression of the thecal cul-de-sac by a hematoma held in place by the Gelfoam. A review of the literature on prevention of adhesions after laminectomy is included. PMID- 1632227 TI - Aplasia of the anterior cruciate ligament with a compensating posterior cruciate ligament. AB - Aplasia of the anterior cruciate ligament is a rare condition and is usually associated with other abnormalities of the lower extremities. We report aplasia of the anterior cruciate ligament with a compensating posterior cruciate ligament in a 15-year-old boy. PMID- 1632228 TI - Tumoral calcinosis. PMID- 1632229 TI - HLA antigens and recurrent acute otitis media. AB - The frequencies of a number of HLA antigens were investigated in 45 individuals with clinical recurrent acute otitis media (rAOM), defined as six or more episodes of AOM during a 12-month period, and were compared to those in a control group from the same district. HLA-A2 was found to occur in 80% of the rAOM group, as compared to 55.9% of controls (p less than 0.01). HLA-A3 antigen occurred in only 11.1% of the rAOM group in contrast to 27.5% of controls (p less than 0.05). Among 22 prospectively followed children without any AOM during their first 3 years of life, the frequencies of HLA-A2 and HLA-A3 antigens were comparable with those among controls. PMID- 1632230 TI - Results of uvulopalatopharyngoplasty in snoring. AB - Twenty-one patients (4 females and 17 males) with very annoying snoring were subjected to UPPP with CO2-laser technique. All patients were overweight (bodymass index average 30.3 kg/m2). In 71%, narrowing were found at the naso/oropharyngeal border. All had either abnormal uvula or soft palate. In 17 patients, snoring was reduced to a degree no longer socially annoying. Three were annoying to some extent. In only one patient, snoring was completely unchanged. UPPP is not very difficult to perform and we did not notice any troublesome sequelae. We think that UPPP is an effective operation for severe snoring, although it does not eliminate the symptom. PMID- 1632231 TI - Diagnosis of psychogenic dysphonia. AB - Background factors, symptoms and signs were analysed in 40 consecutive patients with psychogenic dysphonia. Their voice profile was compared with that of 40 patients with infectious laryngitis. The majority of the patients were young females, non-smokers, who were not professional voice users. Criteria for acute infectious laryngitis prior the voice disorder were met in no more than 10% of the patients. Nevertheless as many as 40% of the patients had been treated with various antibiotics. The prevalence of reported asthma/allergy-like symptoms was high, 37.5%. Perceptual analysis of voice profiles demonstrated similarity of aberrancies in psychogenic dysphonia and in acute laryngitis. Since it may be difficult to distinguish psychogenic dysphonia from acute laryngitis, careful analysis of anamnestic data may be helpful for a correct diagnosis. PMID- 1632232 TI - Computerized apnea detection in ambulatory sleep recording with the Somnolog system. AB - Apnea detection from a traditional polysomnographic sleep recording is tedious and time consuming. With a new portable device, the Somnolog, it is possible to make ambulatory sleep recording and apnea detection. PMID- 1632233 TI - Bilateral facial palsy caused by the Borrelia spirochete. AB - A case of total left peripheral and partial right peripheral facial palsy caused by the Borrelia spirochete is presented. The diagnosis was confirmed by the history of the tick-bites and elevated titers of IgG in serum and cerebrospinal fluid. PMID- 1632234 TI - Alternative treatment of obstructive sleep apnea: nasal-CPAP continuous positive airway pressure. AB - The upper airway of patients with obstructive sleep apnea is often characterised by a narrow lumen and increased compliance of the pharyngeal wall. During inspiration, a negative inspiratory pressure is developed which may produce occlusion in the pharynx. Continuous positive airway pressure (CPAP) works as a pneumatic splint dilating the upper airway and thus keeping the airway open. The result is a patent airway, free regular breathing during sleep with no oxygen desaturations and normal sleep architecture. Irregular pulse, fluctuations in blood pressure, increased levels of catecholamines recorded during sleep in patients with obstructive sleep apnea are normalised during CPAP treatment. PMID- 1632235 TI - Shortened reaction time during nasal CPAP treatment of obstructive sleep apnea. AB - In 5 patients with severe obstructive sleep apnea the effect of nasal continuous positive airway pressure (CPAP) treatment on daytime functioning was measured. During a 2-week period, when the patients were effectively treated with nasal CPAP, a shortening of the reaction time could be measured. PMID- 1632236 TI - Natural history of Bell's palsy. PMID- 1632237 TI - Penicillin V treatment of experimental pneumococcal otitis media prevents mucosal changes. PMID- 1632238 TI - [Patient compliance in clinical research in the primary and secondary sectors]. PMID- 1632239 TI - Pressure recordings--a method for detecting site of upper airway obstruction in obstructive sleep apnea syndrome. AB - Polysomnography is the method of choice in diagnosis of obstructive sleep apnea syndrome (OSAS) establishing whether a patient has apneas or not. It does not, however, give any indications of where the obstructions occur. This is reflected in the limited success rate of current surgical procedures used in the treatment of this disorder. We have developed a simple method for simultaneous determination of OSAS and site of obstruction. The method implies continuously recording of pressure at different sites in pharynx. A catheter with five pressure transducers and corresponding markings is put into the pharynx through the nasal cavity and interfaced with a polygraph. Continuous pressure registrations were made in 12 patients. We have found characteristic patterns of pressure-changes which clearly indicate the level of obstruction. This may be of importance in selecting patients for further treatment. PMID- 1632240 TI - Orbital floor fractures. Diagnosis, treatment and results. PMID- 1632241 TI - Acute orbit from ethmoiditis drained by endoscopic sinus surgery. AB - Orbital complications from sinusitis are briefly reviewed. Acute orbit is suggested as the common term for all stages in the development. Four patients with acute orbit and ethmoiditis are presented. All had transnasal ethmoidectomy and drainage of the orbit performed by functional endoscopic sinus surgery (FES). Surgical indications are discussed based on clinical signs and CT examination. The operation can easily be staged according to the needs of the individual patient, starting with drainage of the primary cause, the sinusitis. Orbital skin incisions are avoided. Postoperative regression of clinical symptoms has been rapid. PMID- 1632242 TI - Histochemical analysis of enzymes involved in the formation and metabolism of the nasal septal cartilage. AB - Formation of the nasal septal cartilage in prenatal and neonatal rats was studied histologically and by histochemistry to determine the manner, degree and participation of the nasal septal cartilage in midface growth and in bone formation of the face. Chondrogenesis of the nasal septal cartilage started at the 13th embryonic day, premaxillary and vomerin bone formation at the 14th embryonic day and endochondral bone formation of the septo-presphenoid area at the 17th embryonic day. After differentiation of the nasal septal cartilage, this cartilage supported ethmoid bone formation by endochondal ossification in the septo-presphenoid area. Nasal septal cartilage showed intense activity of lactate dehydrogenase, NADH2-diaphorase and a moderate activity of acid phosphatase, whereas premaxillary and vomerin bone showed intense activity of alkaline phosphatase. Osteoblasts showed intense activity of alkaline phosphatase, lactate dehydrogenase and NADH2-diaphorase and osteoclasts showed intense activity of acid phosphatase. During the embryonal period growth of the nasal septal cartilage could occur in an ethmoido-rostral direction supported by endochondral ossification and growth in length and height supported by apposition and interstitial growth. PMID- 1632243 TI - Treatment of snoring--with and without carbon dioxide laser. AB - Thirty patients with bedpartners complaining of their heavy snoring which had resulted in separate bedrooms were treated surgically. Three different methods were used, each group consisted of 10 patients. In group A conventional scalpel excision was used for uvulopalatopharyngoplasty including tonsillectomy. In groups B and C, patients with small tonsils were selected and therefore the tonsils were saved. Group B was operated with carbon dioxide laser under a microscope and using micromanipulator. The same kind of excision was used as in group A but the tonsils were saved. Group C was operated as group B but using conventional scalpel excision technique. With a starting-point of snoring score 3 preoperatively in all groups, the mean postoperative snoring score in Group A was 1.0, in Group B 0.2 and in Group C 1.1. Patients with postoperative snoring scores of 0 and 1 were regarded as successful responders to surgery. No serious side effects were noted due to treatment. PMID- 1632244 TI - Quantitative assessment of esophageal transport with normalized condensed images. AB - Scintigraphy is one of several diagnostic procedures used to investigate dysphagia. Several different methods to present the bolus transport have been presented. The normalized condensed image enables quantitative assessments of patterns of bolus transport and a descriptive nomenclature of these patterns: the "L-h-S-E-m-system", based on results of 25 subjects without dysphagia, is suggested. Aberrant patterns were found in 40% of the swallows. PMID- 1632245 TI - Primary mandibular reconstruction after ablative cancer surgery. AB - Restoring of the oral functions is one of the most complicated procedures in head and neck cancer surgery. For the moment "primary reconstruction" using functionally stabile reconstruction plates in recontouring and stabilizing of the remaining mandibular stumps after tumour extirpation is becoming increasingly popular. The aim of the present study was to evaluate treatment results and complications of primary reconstruction after major tumour surgery. PMID- 1632246 TI - Influence of allergy, asthma and hypertension on nasal polyposis. AB - Arterial hypertension was found in 78 of 224 consecutive patients operated for nasal polyposis. An exacerbated degree of hypertension was significant in groups aged above 50 years. In total, 46% of patients whose nasal polyposis lasted for more than 10 years suffered from hypertension. Fifty of 78 patients developed hypertension after nasal polyposis had been established, and the mean duration time from polyposis to hypertension was 11.1 years. Eosinophilic infiltration was found in 88% of nasal polyps. Of the patients with eosinophilic polyps, 34.8% were classified as atopic. The most common allergens were house dust, tree- and grass pollen, mite and acetyl salicylate. Hyposensitization against known allergens reduced necessary polypectomy frequency in 60% of patients. The third most common concurrent disease was asthma (26.1%). Ten cases of the triad: asthma, intolerance to acetyl salicyclic acid and nasal polyps were found, comprising 4.4% of all patients. Fifty percent of these patients also had hypertension. This investigation strengthens earlier studies that hypertension is not an aetiologica factor for nasal polyposis but can develop secondary to nasal obstruction. PMID- 1632247 TI - Diagnosis and treatment of fractures of the orbital floor. A ten-year retrospective study. AB - In a retrospective study of 42 patients treated for fractures of the orbital floor at Sodersjukhuset, different diagnostic methods and the final outcome of the treatment were evaluated. Motility evaluation and exphtalmometry were performed on all patients by the same ophtalmologist. Twenty patients underwent computed tomography with coronal scans. The prolapse and volume of the herniated soft tissue from the orbit and the degree of entrapment of the inferior rectus muscle were measured from the CT scans. All patients who developed enophtalmos had according to the CT scans herniated volumes exceeding 0.7 ml. Only 2 out of 9 patients, who did not develop enophtalmos had herniated volumes exceeding 0.7 ml. This difference was statistically significant. Of these patients 36 were operated, while 6 patients were only followed. The mean follow-up time was 6 months. Out of 39 patients followed for more than 3 months, 28 were symptom free. Six patients were moderately molested by diplopia or enophtalmos. Five patients suffered from a persistent clinically significant diplopia or enophtalmos. PMID- 1632248 TI - Cellular regeneration and recovery of the maxillary sinus mucosa. An experimental study in rabbits. AB - Unilateral maxillary sinusitis was induced in 30 New Zealand White rabbits with Streptococcus pneumoniae or Bacteroides fragilis. In another group of 15 rabbits without infection, the sinus mucosa was surgically removed in defined areas. In both series, the sinuses were serially sectioned for histological analysis of the cellular regenerative capacity. In maxillary sinusitis induced by Bacteroides fragilis, an inflammatory and also reparative process involving all mucosal layers including the underlying periosteum was seen. The more superficial trauma as found in pneumococcal sinusitis eventually led to restitution ad integrum. Following surgical removal, the denuded sinus-lining was reepithelized by a flattened ciliated epithelium on a lamina propria displaying fibrosis and lacking serous glands. The restoration of the rabbit maxillary sinus mucosa after surgical trauma thus leads to structural abnormalities of the epithelium as well as the lamina propria, and these changes are likely to interfere with the normal function of the sinus mucosa. PMID- 1632249 TI - The bone-anchored hearing aid. Osseointegration and audiological effect. AB - The results of treatment of the first 12 Danish patients with the Branemark titanium implant system and the bone-anchored hearing aid (BAHA) are reported. All implants were osseointegrated, judged by 99mTC-scintigraphy, X-ray examination and clinical examination. Skin reactions were few, transient and short lasting. The patients experienced the BAHA to be superior to both conventional BC hearing aids and AC hearing aids in practically all respects. Speech discrimination scores in quiet and in noise were similar for the 3 types of hearing aids. PMID- 1632250 TI - Glossopexia--evaluation of a new surgical method for treating obstructive sleep apnea syndrome. AB - Uvulopalatopharyngoglossoplasty, UPPGP, is a modification of the uvulopalatopharyngoplasty, UPPP, technique, originally used for surgical treatment of the obstructive sleep apnea syndrome. The first method seems to be the more successful. However, polysomnography performed after UPPGP showed that about 35% of the patients still had obstructive apnea periods during sleep. Eight of these patients were reoperated with a new technique which is a combination of partial tongue resection and anterior suspension of the tongue (glossopexia). After glossopexia all the patients were subjectively relieved of their symptoms. However, polysomnography carried out postoperatively demonstrated that only 2 patients were objectively cured. The authors want to stress the necessity of meticulous polysomnographical registration pre- and postoperatively. Subjective and objective parameters recorded before and after surgery are discussed. PMID- 1632251 TI - Palatopharyngoglossoplasty in the treatment of patients with obstructive sleep apnea syndrome. AB - A new technique (palatopharyngoglossoplasty (PPGP)) has been developed for surgical treatment of patients with the obstructive sleep apnea syndrome (OSAS). In 20 operated patients 18 reported immediate marked improvement of daytime sleepiness, alertness and vigilance during the day, and of working capacity. However, polysomnography carried out pre- and postoperatively showed that only 10 patients were "cured", defined as 50% or more reduction in apnea/hypopnea index (AHI). Cephalometric analysis pre- and postoperatively indicated that nonresponders had a long and narrow posterior airway space, and we suggest that during sleep this part of the upper airway collapses before as well as after the operation. The discrepancy between the subjective improvement observed after PPGP and the postoperative reduction in AHI may be due to reduced/eliminated snoring and/or improvement in sleep quality after the operation. PMID- 1632253 TI - A new Finnish computerized rhinomanometer. AB - We introduce a new sophisticated Finnish rhinomanometer in which the need for routine work has been minimized. Technical information about the instrument is given, recording procedure is described and a normal material and reproducibility test is analyzed. PMID- 1632252 TI - Acute laryngitis in adults: results of erythromycin treatment. AB - Previous studies of acute laryngitis in adults have shown high nasopharyngeal isolation rates of B. catarrhalis and H. influenzae. Phenoxymethylpenicillin had no effect on the clinical course. In the present study, 106 patients with acute laryngitis were treated with erythromycin 0.5 g x 2 V or placebo. During the first week the isolation rate of B. catarrhalis was reduced from 60 to 10% in the erythromycin group compared to 34 to 27% in the placebo group (p less than 0.01). The elimination of H. influenzae, isolated in 19% at the acute visit, did not differ between the two groups. As compared to controls, erythromycin treated patients reported significantly lower scores of subjective voice disturbance after 1 week and cough after 2 weeks. Laryngological examination and voice evaluation failed to reveal any differences between the groups. PMID- 1632254 TI - Nasal packing and nocturnal oxygen desaturation. AB - Nasal obstruction influences respiration during sleep, and nasal packing may be the cause of obstructive sleep apnoea. In order to investigate this phenomenon, perioperative nocturnal oxygen saturation was monitored for 3 nights with continuous, non-invasive pulse oximetry in 12 patients who had total nasal packs after septoplasty. Significant extension of nocturnal accumulated time of oxygen saturation less than 90% was demonstrated both during the first and second postoperative nights. The clinical significance of these results is as yet unknown, but the use of partial nasal packing in association with septoplasty is advocated and further investigations on nocturnal oxygen saturation are called for. PMID- 1632255 TI - EMLA in local anaesthesia of the tympanic membrane. AB - An ideal agent for local anaesthesia of the tympanic membrane has been missing so far. Recently, however, a eutectic mixture of lignocaine and prilocaine (EMLA, Astra, Sodertalje, Sweden) has proved promising. We compared the anaesthetizing efficacy of EMLA, Bonain's solution (cocain, menthol, phenol ana partes) and Xylocain-spray (Astra, Sodertalje, Sweden) in 42 voluntary subjects. EMLA was applied on one tympanic membrane and either one of the other two agents in the other ear of each subject. Small cotton pledgets were used for application. Sensitivity of the ear drum was tested under otomicroscope with a cotton tipped wire before and after each local anaesthesia. Full anaesthesia could be reached with EMLA very significantly (p less than 0.001) more often than with Xylocain and almost significantly (p = 0.057) more often than with Bonain's solution. Most of the test subjects preferred EMLA to Bonain's solution of Xylocain. Undesired side effects, including two tympanic membrane perforations, appeared in most of the ears anaesthetized with Bonain's solution. In the clinical part of the study, EMLA topical anaesthesia was used in 127 minor policlinical tympanic membrane procedures like myringotomy and tympanostomy tube assembling. Eighty-three of the procedures were assessed as painless, 36 unpleasant and 8 painful. A 30-min action time of EMLA was considered sufficient in most cases. No EMLA related side effects appeared. In conclusion, Bonain's solution is recommended to be replaced by EMLA or a corresponding agent for local anaesthesia of the tympanic membrane. PMID- 1632256 TI - Penicillin tolerance in group A streptococci and treatment failure in streptococcal tonsillitis. AB - Penicillin tolerance in Streptococcus pyogenes has been suggested as a possible cause of therapeutic failure in streptococcal phryngitis treated with penicillin. In 144 patients with acute group A streptococcal tonsillitis treated with phenoxymethyl penicillin 12.5 mg per kg body weight b.i.d. for 10 days the same T type was recovered after treatment in 21%. The recovery rate was higher for non tolerant strains, 23%, than for tolerant strains, 10% (p greater than 0.05). Of patients with a non-tolerant strain 17% had both clinical and bacterial treatment failure in comparison with 5% infected with a tolerant strain (p greater than 0.05). Reinfection with a new serotype occurred in altogether 3%. The present data did not indicate that penicillin tolerance in group A streptococci is of significance in acute tonsillitis treated with phenoxymethylpenicillin for 10 days. PMID- 1632257 TI - Acute respiratory tract infections in early childhood. PMID- 1632258 TI - Prognostic factors in oral cavity carcinomas. AB - This retrospective study of 176 patients with oral cavity carcinoma showed that nearly 60% of the patients presented with an advanced stage of disease. The duration of symptoms was shorter in patients with a large tumour than with a small (p less than 0.001) and in patients with metastases than in those without (p less than 0.01). Lymph node metastases were more common in large tumours (p less than 0.01), in tumours with high malignancy grading (p less than 0.05) and in non-diploid tumours (p less than 0.001). The presence of lymph node metastases (p less than 0.001), tumour size (p less than 0.01) and tumour DNA ploidy (p less than 0.005) were the only parameters that significantly influenced survival (Cox regression analysis). PMID- 1632259 TI - Spontaneous otoacoustic emissions. Short-time stability. AB - We have examined 307 spontaneous otoacoustic emissions (SOAEs) from 59 ears. The short-time amplitude stability was very good, especially in the high-frequency region. A statistically significant trend for emissions to influence other emissions could not be demonstrated. PMID- 1632260 TI - Ostial function in allergic rhinitis. AB - In order to evaluate the maxillary ostial function a double-blind, group comparative study with intranasal budesonide and placebo was carried out in 20 adult patients suffering from seasonal rhinitis. The trial started with an entry visit 3 weeks before pollen peak with clinical assessments (physical examination and ostial diameter measurements) followed by a 3-week treatment period. Treatment was either intranasal budesonide 200 micrograms b.i.d. or matching placebo b.i.d. The trail ended at pollen peak with clinical assessment. The results showed normal ostial diameters in the patients suffering from seasonal rhinitis. There were no statistical significant differences in ostial diameter change between the treatment groups except between budesonide and placebo in sitting position at measurement time 0 min. It seems that pollen does not reach the ostial region. PMID- 1632261 TI - Uvulopalatopharyngoglossoplasty (UPPGP) in the treatment of the obstructive sleep apnea syndrome. AB - Out-patient polysomnography was conducted prior to surgery in 26 male, obstructive sleep apnea patients. Resection of lateral aspects of the tongue base and conservation of the proximal part of the uvula muscle were carried out in addition to conventional palatopharyngoplasty. At a minimum of 6 months after surgery, the patients were given a questionnaire for assessment of treatment. At the same time, polysomnography was repeated for objective evaluation of the results of surgery. More than 90% of the patients were satisfied with the outcome of treatment. The objective results by means of apnea index and oxygen desaturation index matched the patients' personal experiences, which is not usual in this kind of treatment. Sixty-seven percent of the obstructive sleep apnea patients achieved more than a 50% reduction in apnea index and oxygen desaturation index. No more side effects than for similar surgical intervention (PPP) were encountered. Safety and efficiency lead us to recommend this procedure as standard whenever oropharyngeal surgery is indicated. PMID- 1632262 TI - Experience with the Wurzburg titanium miniplate system in maxillo-facial surgery. AB - Since late summer 1989 we have used the Wurzburg titanium miniplate system in the treatment of severe midface fractures and as implants in reconstruction of the mandible after cancer surgery of the mouth. The aim of this study was to test the applicability of the system. PMID- 1632263 TI - [Healing of tympanic membrane perforation-a complex process influenced by a variety of factors]. AB - It is known that the healing of a perforated tympanic membrane can be influenced by mechanical procedures as well as drugs. Animal experiments have recently shown that local treatment with steroids delays the healing of a tympanic membrane perforation, whereas hyaluronan (hyaluronic acid) improves the healing rate as well as the quality of the scar. Hyaluronan, a non-sulphated glycosaminoglycan, belongs to the extracellular matrix substances. In the present study another glycosaminoglycan--heparin--was applied on experimental tympanic membrane perforations. This report confirmed that also this extracellular matrix substance improves the healing rate of a tympanic membrane perforation and the scar quality. PMID- 1632264 TI - Magnetic facial nerve stimulation in normal subjects. Three groups of responses. AB - Magnetic stimulation provides a method to stimulate the facial nerve transcranially. With this method, the stimulation can be directed to the intracranial part of the facial nerve, whereas conventional electric stimuli are delivered to a more peripheral part of the nerve. In 40 healthy subjects, ipsilateral responses with latencies of 4.5 +/- 0.4 ms were recorded on the nasolabial folds. The latencies were 1.1 ms longer than those elicited at the stylomastoid foramen by electric stimulation. Furthermore, a response with a mean latency of 12 ms (range 10-16 ms) appeared in 6 out of 10 healthy subjects and a polyphasic response with a mean latency of 32 ms in 9 out of 10 of these subjects. Transcranial magnetic stimulation seems to allow the examination of motor conduction through the proximal part of the facial nerve. In addition, the method may give further information concerning the facial activation mechanisms possibly by other central pathways. PMID- 1632265 TI - [An anastomotic loop between the recurrent nerves--an anatomical description]. AB - The authors present the results of twelve dissections of the neck carried out during autopsy on non-conserved human corpses. The investigation, centered on the anatomic study of the laryngeal nerve within the framework of the European Research Group on the Larynx (G.R.E.L.), revealed the presence of a connecting nervous anatomic branch between the recurrent laryngeal nerves which was observed in 10 of the 12 corpses examined. Despite a revision of national as well as international literature concerning ramifications and anastomosis of the recurrent laryngeal nerves, the authors were unable to find description of this anastomotic ansa. The anatomic reliefs related to this branch are extremely interesting, although research is still in its initial phase. This ramification is situated between the trachea and the oesophagus and the location of the branching-off point from the recurrent nerves as well as the crossing point of the nervous bundle with the oesophagus-tracheal axis vary greatly. The detachment of the ansa from the recurrent trunk is located at the intrathoracic level, while the crossing with the posterior paries of the trachea is located in proximity of the cervicomediastinal junction. The constant presence of this nervous entity encourages us to continue and extend our research, most of all towards microscopic and ultrastructural anatomy as well as towards histomorphometric studies which can give us precious indications. Moreover, electrophysiological studies are in program so as to enable us to gather the largest amount of useful data regarding any possible use of this anatomic entity. PMID- 1632266 TI - [The quantitative study of nucleolar organizers (AgNOR) in the diagnosis of laryngeal dysplasias and in the assessment of the prognosis in invasive carcinoma]. AB - Nucleolar organiser regions (AgNOR) are chromosomal segments in which ribosomal RNA is codified. These structures can be identified in the nuclei of cells in routine histological sections using a silver staining technique which reveals the proteins associated with transcription RNA. The number of AgNOR identified depends on the state of cell proliferation. The purpose of the present study was to evaluate the distribution of AgNOR in normal laryngeal mucosa, dysplastic and neoplastic, in order to establish a possible correlation with the degree of dysplasia and/or the entity of the malignant lesions. Ten slides each of specimens of laryngeal carcinoma, serious dysplasia and middle dysplasia were prepared with the silver staining technique. A count of the NOR in the basal, parabasal, intermediate and superficial levels was made. Findings show an increase in the average value of NOR proceeding from normal tissue to carcinoma in situ and malignant carcinomas. The number of AgNOR was lower always than that observed in the parabasal level. In the intermediate cell section the number of AgNOR was inferior to that in the parabasal level in normal tissue as well as in middle dysplasia, while it remained high in serious dysplasia and in carcinomas, thus indicating a great deal of biological activity in these cases. This method can be employed in order to better individualize those dysplastic lesions which, because of their tendency towards malignancy, must be kept under observation by means of an extremely accurate follow-up. PMID- 1632267 TI - [Magnetic fields evoked by auditory stimuli: a normative study]. AB - After outlining the fundamentals of biomagnetism and their possible clinical applications, the authors report the results of a normative study on auditory magnetic fields performed on 18 normally hearing subjects between the ages of 25 and 30. Having presented a thorough review of the literature, they then describe the recording technique employed, the dcSQUID biomagnetic system for signal detection, the shielded room, the characteristics of the stimulus. The auditory magnetic response is characterized by three main waves (P4Om, N100m, P200m) whose latency and amplitude values were calculated. Moreover, in order to localize dipolar activity, certain parameters, such as P and T, were taken into consideration. Localizations were made using a spherical volume conductor or with MRI, which was in any case employed in all the subjects. The waves, especially the N100m recorded contralaterally to the stimulus, showed a reduced latency and an increased amplitude when compared to those recorded ipsilaterally. Moreover, a systematic posterior shift of the N100m source into the left hemisphere with respect to the right one was detected. In conclusion, the authors emphasize the need to study electric as well as magnetic responses in order to better understand auditory cortical functions. PMID- 1632268 TI - [Bidirectional horizontal and tridimensional apogeotropic nystagmus: 2 semeiological realities]. AB - The authors take into account two different types of stationary, persistent and direction-changing nystagmus (ny): 1) the horizontal bidirectional ny (nyOB), apogeotropic (nyOBA) and geotropic (nyOBG); 2) the tridirectional apogeotropic ny (nyAT). The nyOBA was identified in experimental studies in 1973 but no other studies on the subject have been published since then. In existing literature the nyOBG has been reported in only one paper, whereas the nyAT has not yet been studied at all. The nyOBA is the combination of a 2nd degree left ny with the head turned right and a 2nd degree right ny with the head turned left. The nyOBG is the combination of a 2nd degree right ny with the head turned right and a 2nd degree left ny with the head turned left. The nyAT is a 2nd degree apogeotropic ny noticeable with the head turned left, right and in the position of Rose (head hanging down). From among a total of 5,960 consecutive vestibular examinations performed from 1986 to 1990, the authors chose those presenting nyOBA, nyOBG and nyAT and discuss them in the light of other vestibular findings and clinical diagnosis. A routine vestibular examination aims at verifying an eventual, spontaneous/evoked ny with the head turned right and left, in the position of Rose and in the two rapid Hallpike positionings. Frenzel glasses are used for detecting the gaze and rebound ny and these, in turn, are checked for visual fixation. During the caloric stimulation, according to the Fitzgerald-Hallpike method, the ny visual suppression test is performed at the culmination period. When electronystagmography is performed, visual oculomotor reflexes are often tested as well. The nyOB and/or nyAT were observed in 3.9% of the patients (234 subjects). The nyOB was present in 177 patients as follows: apogeotropic ny in 128 and geotropic in 49. This was the only vestibular finding in 46.9% of the nyOB cases (83 out of 177 patients). The nyAT was observed in 57 patients and in 17.6% of them was the only pathological finding of the otoneurological examination. When nyOB or nyAT were observed, clinical diagnosis evidenced their central origin in 138 of the 234 patients, most frequently present in cranial trauma, vertebral-basilar vasculopathy and multiple sclerosis. In a limited number of cases some sign of peripheral vestibulopathy were also observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1632269 TI - [An evaluation and comparison of the methodology of 2 otophoniatric screenings performed in the 1989-1990 biennium on a sample of 4-year-old children attending nursery schools]. AB - The Pediatric Otophoniatric Department of U.S.L.75II, the Multicenter of Preventive Medicine in Via Cherasco, 5, Milan, carried out two otophoniatric screenings on about 70 four-year-old nursery school children. While this screening was considered experimental in four schools, the ultimate goal is to extend it to all the nursery schools in the same area. The primary aim of the screening was to individualize several pathologies of the upper respiratory tract in this age range. The second aim was to identify language pathologies in children under the age of six in order to treat them as soon as possible with adequate and preventive therapy and appropriate language re-education before their entrance into primary school. The materials and methods employed were as follows: O.R.L. examination: otoscopy, rhinoscopy, oropharyngoscopy, indirect laryngoscopy (after individualization of dysphonia); Audiometric test: peep show in free field with a 250 Hz-4000 Hz frequency range at 30 dB; Language evaluation through examination and interpretation of questionnaires formulated in order to evaluate language development filled in by the children's teachers. Two modifications in the method used in the 1989 study were made in the 1990 screening: The preventive use of an auditory duct cleaner and the distribution of the above-mentioned questionnaires at the very beginning of the study. These two changes improved screening planning as well as development. The results of the two screenings were compared and an increase in the percentage of children examined and subjected to the audiometric test was noted. In fact, in the 1989 study, only 77% of the children underwent the audiometric test (23% had ear wax), while in the 1990 study 100% underwent the test (ear cleaner had been used). With regard to the questionnaires, the data were gathered four months after screening in the 1989 study, whereas in the 1990 study this phase was carried out on the same day of the screening. The new methodology saved time in the screening. PMID- 1632270 TI - [The senile voice]. AB - Involutive processes which characterize aging induce substantial morphological and functional alteration in the pneumo-phono-articulatory system and thus bring about numerous effects on vocal quality. Fundamental frequency (Fo) variation, whose values increase in males and decrease in females, are found in voice patterns. Moreover, in literature many authors have described vocal substain intensity and timbre deficit in the elderly. Vocal emission of elderly people can become so peculiar that it may be possible to identify approximately the age and the sex of the speaker by merely hearing the voice. The aim of this work was to identify specific parameters of the senile voice using spectroacoustic digital analysis. The following points were considered in this study: the psychoacoustic perceptive evaluation of vocal samples in subjects of different ages in order to identify the sex and age of the speaker; the spectroacoustic digital analysis of the same vocal samples; the morphofunctional observation of the phono articulatory apparatus. Our results confirmed the presence of peculiar electroacoustic characteristics in the senile voice (mean pitch value variation in males and in females, vocal substain deficit, decrease in vocal intensity, senile tremolo, cycle-to-cycle alteration of Fo and mean amplitude) due to morphofunctional changes of the pneumo-phono-articulatory system. In all the subjects we observed anatomo-functional changes at the glottic level. The presence of specific vocal patterns and the quality of speech play an important role in the processes of senile voice identification. PMID- 1632271 TI - [Gardner's syndrome: a case report]. AB - The Gardner syndrome (GS) is a dysplasia in which neoformations in the intestines, soft tissue and osseous tissue are associated. Since extra-intestinal manifestations, in particularly osteomas, appear promptly even in infants, and above all in the light of the possibility of malignant degeneration, the presence of mandibular osteomas indicates the necessity of carrying out investigations in order to ascertain the eventual existence of an intestinal polyposis typical of GS. This study describes a typical case of GS diagnosed merely upon suspicion of the existence of the syndrome in a patient who came to our Department with a mandibular osteoma. The study underlines the importance not only of carrying out investigations in order to ascertain the presence of GS (rectocolonoscopy), but also that of studying the relatives of the patient in light of the fact that this particular dysplasia is transmitted genetically. PMID- 1632272 TI - [Rehabilitation of oro-pharyngeal dysphagia of neurogenic etiology using radiological examination: preliminary results]. AB - Dysphagia is more frequently observed in patients with neurologic diseases (stroke, bulbar or pseudo-bulbar syndrome, amyotrophic lateral sclerosis, cranial trauma). Furthermore, the presence of this pathology is obviously more frequently noted in the light of the increase in the length of the human life span. It has become evident that alternative feeding procedures such as the nasogastric tube or gastrostomy may bring about complications and deprive patients of the oral phase of deglutition which plays a leading role in stimulating digestive functions. The Authors report a systematic research on the rehabilitation aspects of neurogenous dysphagia. All the patients studied underwent a neurological examination and oropharyngeal functional evaluation using echo-videorecording of the oral phase of deglutition and fluoro-videorecording of the pharyngeal phase. The data obtained allowed for the selection of five patients considered suitable for the rehabilitation program. One of them had a multi-infarct encephalopathy, two a spastic hemiplegia f.b.c., a fourth a cerebellar syndrome and the last a sequela of meningioma removal of the ponto-cerebellar angle with peripheral paralysis of the right VII, IX, X, XI cranial nerves. This last patient also underwent a crico-pharyngeal myotomy. Therapy consisted in making the patient sensitive to swallowing movements and in training them to assume a compensatory posture as well as functional rehabilitation of the organs involved in deglutition. The first datum emerging from the study is the lack of etiological homogeneity found in the cases treated with evident variability in different deglutition organ impairment, even though there was the common denominator of the dysphagia symptom. With regard to the results obtained, there was a complete resolution in one patient, while in the other four there was such an improvement as to allow the patients a safe autonomous oral assumption of food. The positive results obtained are not only linked to the recovery of damaged organs, but also to the development of compensatory strategies such as the choice of appropriate food consistency and the assumption of postures which protect the respiratory tract from aspiration and favor crico-pharyngeal relaxation. PMID- 1632273 TI - Age-related changes in NMDA-induced [3H]acetylcholine release from brain slices of senescence-accelerated mouse. AB - From the brain slices of normal mice (ddY strain, subcloned from dd strain in National Institute of Health in Japan), N-methyl-D-aspartic acid (NMDA) at 0.01-1 mM evoked [3H]acetylcholine (ACh) release in a concentration dependent manner. [3H]ACh release evoked by 1 mM NMDA was significantly inhibited by 2-amino-5 phosphonovaleric acid (APV), phencyclidine (PCP) and 5-methyl-10,11-dihydroxy-5H dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801). The effects of NMDA were not seen in the Ca2+ free medium and were inhibited by physiological concentration (0.83 mM) of Mg2+. NMDA seems to cause ACh release from nerve terminals through the receptor-ion channel mediated mechanism in the mouse brain. Based upon these results, we determined the activity of a high K(+)- or NMDA-evoked [3H]ACh release using prone/8 strain of senescence-accelerated mouse (SAM-P/8) (a murine model of accelerated aging and memory dysfunction) and SAM-resistance/1 strain (SAM-R/1) (normal aging mice as the control) and these release activities were compared between both strains and during aging. [3H]ACh release evoked by 30 mM KCl was significantly lower than that of age-matched SAM-R/1 at 9 and 12 months. NMDA evoked the [3H]ACh release at 2, 6, 10 and 14 months in R/1 mice. In SAM-P/8 mice the activity of NMDA-evoked release was seen at 2 months, but markedly decreased afterwards. Nonsignificant difference was observed on the uptake of [3H]choline and on the spontaneous release of [3H]ACh between SAM-P/8 and SAM-R/1 strains, and during aging.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632274 TI - Quantitative histochemical changes in enzymes involved in energy metabolism in the rat brain during postnatal development. II. Glucose-6-phosphate dehydrogenase and beta-hydroxybutyrate dehydrogenase. AB - The postnatal maturation of glucose-6-phosphate and beta-hydroxybutyrate dehydrogenase activity was assessed by histochemistry in rats at eight postnatal stages, P0, P5, P10, P14, P17, P21, P35 and the adult stage. Enzyme activities were revealed on cryostat brain sections with nitroblue tetrazolium. Both enzyme activities were low and homogeneous at birth, and increased to reach a peak in all areas studied, at P17 for beta-hydroxybutyrate dehydrogenase and at P21 for glucose-6-phosphate dehydrogenase. Then, glucose-6-phosphate dehydrogenase activity decreased regularly by 20-49% from P21 to adult stage, except in cerebellar white matter where activity did not change after P21. beta hydroxybutyrate dehydrogenase activity decreased regularly from P17 to adult stage in globus pallidus, hippocampus, thalamus, brainstem, genu of corpus callosum and cerebellar white matter. It sensorimotor cortex, medial geniculate body, caudate nucleus, hypothalamus and inferior colliculus, beta-hydroxybutyrate dehydrogenase activity stayed stable between P17 and P35 and decreased thereafter to adult levels. Finally, in parietal, auditory and cerebellar cortices, beta hydroxybutyrate dehydrogenase activity either stayed stable or slightly increased after P17. The present study shows that there is a quite good correlation between postnatal changes in cerebral glucose-6-phosphate and beta-hydroxybutyrate dehydrogenase activities and the importance of pentose phosphate pathway and ketone body utilization in the developing brain. Our results also reflect the regional heterogeneity of beta-hydroxybutyrate utilization in the adult rat brain, translating into a remaining high activity of beta-hydroxybutyrate dehydrogenase in cerebral cortex. PMID- 1632275 TI - Development of the cholinergic fibres innervating the cerebral cortex of the rat. AB - The ontogeny of innervation of the cholinergic fibres from the basal forebrain into the cingulate, frontal, parietal and piriform cortices of the rat has been examined using a modified histochemical method of acetylcholinesterase (AChE). The method produced crisp fibre staining with enhanced visibility and a clear back-ground, and a pattern of the distribution of these fibres was comparable to that achieved by choline acetyltransferase (ChAT) immunocytochemistry. In the rat, the AChE-stained fibres developed progressively from the deep cortical white matter towards the cortex itself. In general, a few AChE-positive fibres were seen in the subcortical white matter and the cingulum bundle, entering into the cerebral cortex by about 5 postnatal days. The number of these AChE-positive processes increased dramatically during the following two weeks. Thereafter, the general appearance of the overall pattern of distribution of the AChE fibres changed little, but the staining density became gradually more intense and by about 28 days after birth it was virtually indistinguishable from that in the adult. The onset and the development of the AChE-positive fibre network varied considerably between individual cortical regions, and indicated, in general, an anterior to posterior gradient. Within the dispersed AChE fibre network in the cerebral cortex, three bands of relatively enriched cholinergic processes, namely the deep cortical, mid-cortical and superficial layers, developed in an 'inside out' fashion. The exact position of some of these AChE-rich bands varied from one cortical region to another and during development. A striking correlation during ontogeny was observed in the cerebral cortex between the changing patterns of AChE fibre network and the activity of ChAT, the enzyme synthesizing acetylcholine. The present findings can also provide an important anatomical baseline for future studies related to the factors controlling the expression of ChAT activity and the development of cholinergic neurotransmitter system in the rat. PMID- 1632276 TI - Screening of adrenal medullary neuropeptides for putative neurotrophic effects. AB - Chromaffin granules, the secretory organelles of the neuron-like adrenal medullary chromaffin cells, have previously been shown to store and liberate neurotrophic activities that support in vitro survival of several neuron populations including those innervating the adrenal medulla. Molecules resembling fibroblast growth factor and ciliary neurotrophic factor have been identified among these activities. Since chromaffin granules store a variety of neuropeptides and many neuropeptides can have pleiotropic effects on neuronal growth and maintenance we have tested 24 different neuropeptides for their capacities to promote survival of embryonic chick ciliary, dorsal root and sympathetic ganglionic neurons. Peptides tested included several derivatives of proenkephalin (Leu- and met-enkephalin, fragments BAM 22, B, F and E), somatostatin, substance P, neuropeptide Y, neurotensin, VIP, bombesin, secretin, pancreastatin, dynorphin B, dynorphin 1-13, beta-endorphin, alpha-, beta-, and gamma-MSH. Control cultures received saturating concentrations of ciliary neurotrophic or nerve growth factor (CNTF; NGF), or no trophic supplements. At 1 x 10(-5) M leu- and met-enkephalin as well as somatostatin supported sympathetic neurons to the same extent as NGF. At the same concentrations, leu-enkephalin, the proenkephalin fragments BAM 22 and E, and somatostatin maintained about half of the dorsal root ganglionic neurons supported by NGF, but were not effective on ciliary neurons. VIP promoted the survival of approximately 50% of the ciliary and embryonic day 10 dorsal root ganglionic neurons as compared to saturating amounts of CNTF, but required the presence of non-neuronal cells in the cultures to be effective. Neurotensin (1 x 10(-5) M had a small effect on ciliary neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632277 TI - Cellular localization of nerve growth factor-like immunoreactivity in hippocampus and septum of adult rat brain. AB - The cellular localization of the nerve growth factor-like immunoreactivity (NGF LIR) has been studied in the intact adult rat brain at the level of the hippocampus and the septum. Immunolabelling for NGF combined with counterstaining with cresyl violet and double immunostaining technique, which allowed simultaneous localization of NGF-LIR and that of astroglial marker -GFAP, were used. The data indicate neuronal localization of NGF-like immunoreactivity and a lack of colocalization of NGF-LIR with the immunoreactivity of GFAP in the hippocampus. These data are consistent with in situ hybridization results for NGF and immunocytochemical results for pro-NGF localization obtained by others. At the septal level, apart from neuronal localization of NGF-LIR, single NGF-like immunoreactive astrocytes have been observed. This suggests that, although to a very small extent, in vivo intact brain astrocytes may, just as astrocytes growing in vitro, synthesize NGF-like molecules. This finding may be of importance in better understanding the trophic support for NGF responsive cholinergic neurones in the brain. PMID- 1632278 TI - Motor units of medial gastrocnemius muscle in the rat during the fatigue test. I. Time course of unfused tetanus. AB - Time course of tetanus recorded during 40 Hz stimulation was examined on 70 motor units (MUs) of medial gastrocnemius muscle in 41 rats. Three types of MUs were distinguished: slow(S), fast resistant to fatigue (FR) and fast fatigable (FF). In fast MUs of either type, the stimulation induced unfused tetanus with noticeable sag. It was found that in cases of tetani in FF MUs, the sag developed earlier than in FR MUs. Timing of tetanic peak before the sag appeared correlated with contraction time. Some fast MUs demonstrated a distinct time course of tetanus: the weakly accentuated sag appeared early and it was followed by a relatively significant rise in tetanic tension. However, in slow MUs, 40 Hz stimulation induced fused or fused-like tetani. In these MUs the sag was never observed. The obtained results indicate the relation between the sag time course in tetanus and the extent of tetanus fusing. PMID- 1632279 TI - Instability of hemispheric asymmetry in dyslexic children. AB - The study tested the hypothesis of abnormal brain asymmetry in dyslexic children. Two dyslexic groups classified as "phonetic disorder" and "language disorder" and a control group participated in two experiments. In both experiments was employed a dichotic listening procedure consisting in recalling pairs of words presented simultaneously to two ears. In Experiment I the children were to recognize four words presented at a level of loudness typical for natural speech. In Experiment II only two words were used in each trial but they were presented at a low intensity level. The recognition scores for stimuli presented to the left and right ears were compared. In Experiment I all groups of children showed a typical right ear/left hemisphere superiority, i.e. their recognition scores were higher for the right than for the left ear. Dyslexics, however, performed significantly less well. In Experiment II the control children and those from "phonetic disorder" group again performed better when words were presented to their right ears. Unlike those two groups, the children from "language disorder group" showed the right hemisphere superiority, i.e. they performed better in the left ear presentation condition. The results do not support the hypothesis that dyslexic children have abnormal lateralization of verbal functions. They suggest that the pattern of hemispheric asymmetry in dyslexics is less stable and depends both on the kind of dyslexia and on task variation. PMID- 1632280 TI - The effect of some exogenous factors on the formation of intranuclear membranaceus inclusions in the nerve cells. AB - The intranuclear membranaceus inclusions (IMI) appear as encapsulated irregular vacuoles surrounded by a single, rarely double, membrane. The vacuoles include floccular, fine granular content or they are translucent. They were found in neurones of particularly old or very young laboratory animals. Our studies concerning various types of intoxications and ischemia allowed to find relatively large number of such inclusions in laboratory animals. We observed them in four experimental models: (1) cyclo-phosphamide (an alkylating drug) and (2) dichlorvos (phosphoroorganic pesticide) given orally to rabbits, (3) complete ischemia also in rabbits and (4) vincristine (an antimitotic drug) given parenteraly to rats. The IMI were found much more frequently in experimental animals than in controls. We can conclude that intranuclear membranaceus inclusions do not appear to be pathognomonic for any particular etiologic factor, but this factor may influence and distort the homeostasis within nucleus. PMID- 1632281 TI - Biting behaviour as a tactic of escape in two bumblebee species with different nesting habits, Bombus terrestris L. and B. pascuorum Scopoli (Hymenoptera: Apidae). AB - Workers of two bumblebee species, Bombus terrestris L. and B. pascuorum Scopoli, had to find the way of escape out of a test tube closed with a paper membrane stretched against its open end. Nearly all of the tested individuals solved successfully that task by tearing a hole in the membrane closing the tube. However, their escape behaviour showed significant interspecific differences. B. terrestris started biting the membrane sooner than B. pascuorum, and they were biting it more persistently. These behavioural differences matched well the differences in the nesting ecology of these two species. Whereas B. pascuorum is a surface-nesting species, B. terrestris nest in underground cavities connected with the outside world by long tunnels. B. terrestris are thus more likely to be well adapted to deal with obstacles obstructing their way, and/or to have more experience in removing them. Neither the efficiency of biting behaviour as a tactic of escape, nor the total test time differed significantly between the tested species. PMID- 1632282 TI - High production of retinal melatonin in constant darkness. PMID- 1632283 TI - Ontogenesis of muscarinic cholinergic receptor binding in the barrel cortex of mice. PMID- 1632284 TI - Transection of the stria terminalis without damage to the medial amygdala does not alter behavioural sodium regulation in rats. AB - Damage to the medial region of the amygdala has been shown to impair mineralocorticoid-induced sodium appetite, while leaving intact sodium appetite induced through sodium depletion. This effect may result from the interruption of the flow of information through the stria terminalis (ST), a neural pathway linking the medial amygdala with the ventral forebrain. We determined the effect of transecting the ST of the rat, at a point remote from the medial amygdala, on sodium appetite induced with the administration of mineralocorticoids and with the natriuretic furosemide. Similar to control and amygdala lesioned rats, rats with ST knife-cuts displayed a normal sodium appetite following treatment with furosemide. However, unlike medial amygdala lesions, transection of the ST alone did not block mineralocorticoid-induced sodium appetite. Therefore, the inability of mineralocorticoids to induce a salt appetite in medial amygdala lesioned rats does not result from damage to the stria terminalis. PMID- 1632285 TI - Development of the digestive system in the North American opossum (Didelphis virginiana). PMID- 1632286 TI - Thromboxane biosynthesis and metabolism in relation to cardiovascular risk factors. AB - Enhanced platelet biosynthesis of thromboxane A2 is associated with several cardiovascular risk factors, as a consequence of a direct effect on platelet biochemistry and/or some form of endothelial dysfunction. Moreover, episodic increases in thromboxane biosynthesis occur in acute coronary and cerebral ischemic syndromes. Thromboxane-dependent platelet activation represents an important mechanism that amplifies the consequences of acute vascular lesions as well as those of long-standing metabolic or hemodynamic disturbances, and results in increased risk of vascular occlusive events. PMID- 1632287 TI - Effects of daltroban, a thromboxane (TX) A2 receptor antagonist, on lipid metabolism and atherosclerosis. AB - In rat hepatocyte cultures daltroban reduced 14C-acetate incorporation stronger into cholesterol (CH) esters than into free CH. Further data suggest that the reduction of cellular sterols by daltroban is independent from its TXA2 receptor antagonistic activity and caused by reduced capacity of ACAT depending CH esterification. In rabbits fed CH-enriched diet treatment with daltroban led to an inhibition of platelet aggregation and to a significant reduction of progression of atherosclerosis. Both reduced CH esterification and TXA2 receptor antagonism may contribute to the diminution of progression of atherosclerosis by daltroban. PMID- 1632288 TI - Effect of 3-morpholinosydnonimine (SIN-1), NG-nitro-L-arginine (NNA) and NG monomethyl-L-arginine (NMMA) on isolated anaphylactic guinea-pig hearts. AB - In isolated perfused ovalbumin-sensitized guinea-pig hearts modulating effects of nitric oxide (NO) on cardiac function and eicosanoid release were investigated. While the NO-donor SIN-1 exhibited a protective effect during cardiac anaphylaxis, inhibition of NO biosynthesis by NNA or NMMA aggravated anaphylactic changes of cardiac functions. Exogenous and endogenous NO seems to functionally antagonize the effects of vasoconstrictor mediators released during the anaphylactic reaction. In addition, inhibition of cysteinyl-leukotriene (cys-LT) release could contribute to the protective effect of SIN-1 observed. PMID- 1632289 TI - Effect of N-3 fatty acids on eicosanoid formation: implications for platelet thrombotic functions. PMID- 1632290 TI - Influence of omega-3 fatty acids on the prostaglandin-metabolism in healthy volunteers and patients suffering from PVD. PMID- 1632291 TI - Antithrombotic effects of the prostacyclin analogue naxaprostene after oral and intraduodenal application in rabbit carotid artery thrombosis. AB - The antithrombotic efficacy of the prostacyclin analogue naxaprostene has been tested in rabbits with copper coil-induced carotid artery thrombosis. With oral pretreatment, 10 mg/kg naxaprostene prevented thrombotic arterial occlusion; with intraduodenal pretreatment the efficacy of naxaprostene was enhanced and 1 mg/kg was sufficient to exert an antithrombotic effect. The final average carotid blood flow at 180 min compared to the flow immediately before thrombus induction was 85 +/- 25% and 47 +/- 18% in animals treated with 10 mg/kg p.o. resp. 1 mg/kg i.d. naxaprostene. Parallel to the antithrombotic effect, naxaprostene inhibited ADP- and collagen-induced fall in circulating platelets. In anesthetized rabbits there was no dissociation between antithrombotic and hypotensive effects of naxaprostene. PMID- 1632292 TI - Pathophysiology of critical leg ischaemia and mode of action of prostaglandins. PMID- 1632293 TI - Association between total cholesterol and thromboxane B2 levels in offspring of parents suffering from premature coronary artery disease. AB - Relationship between plasma thromboxane B2 concentration and serum total cholesterol level was studied in 129 healthy 3 to 18 years old children, 77 girls and 52 boys, without any family history of premature coronary artery disease and in 181 offspring, 105 girls and 76 boys, of parents suffering from acute myocardial infarction before the age of 45. It was identified an enhancement in serum total cholesterol level of endangered children, and an elevated release of thromboxane A2 in affected girls. A significant negative correlation was found between serum total cholesterol concentration and plasma thromboxane B2 level in healthy girls. However, there was no correlation between serum total cholesterol level and plasma thromboxane B2 concentration in the children whose parents had premature coronary artery disease. It appears, from our results, that this in an alteration of thromboxane A2 release of platelets in children of families with high risk of cardiovascular diseases. PMID- 1632294 TI - Platelet PGI2-receptor behaviour change after treatment with acetylsalicylic acid in healthy volunteers. AB - After treatment of human platelet membrane fractions with different concentrations of acetylsalicylic acid (ASA) the Iloprost binding capacity (Bmax) and also the dissociation constant (Kd) of the high-affinity PGI2-receptor increased significantly (p less than 0.01, low-affinity receptor only an increase of Bmax, p less than 0.01), whereas only a significant (p less than 0.05) increase of the Kd of the high-affinity receptor was observed for intact platelets. PMID- 1632295 TI - Impaired PGI2-stabilization in septic shock patients. AB - Lipids, lipoproteins, apolipoproteins and prostacyclin-half-life (PGI2-T/2) in vitro were determined in patients, who suffered from severe circulatory shock. Extremely lowered lipids, lipoproteins and apolipoproteins and an extremely shortened PGI2-T/2 were found, in these patients. These findings support the data of Yui and Aoyama that apolipoproteins may be an important coregulator of the biological half-life of PGI2 and thereby contribute to hemostatic dyregulation seen in these patients. PMID- 1632296 TI - Association between total cholesterol and plasma thromboxane B2 in human adults. AB - Apparently healthy adults were examined for their lipid and thromboxane parameters. The correlation between the levels of total cholesterol in serum and thromboxane B2/TXB2/ in plasma was strong mainly in men (p less than 0.01). However, the association between atherogenic index /AI/ and TXB2 levels tended to be higher in women. The authors suggest that, in healthy adults, elevated cholesterol levels coexist with abnormalities in thromboxane metabolism. PMID- 1632297 TI - Effects of 9,12,15-octadecatrien-6-ynoic acid on the metabolism of arachidonic acid in platelets and on the platelet aggregation. AB - An acetylenic fatty acid: 9,12,15-octadecatrien-6-ynoic acid (dicranin), extracted from Dicranum Scoparium was preincubated with platelets stimulated by exogenous arachidonic acid (20:4 n-6). Dicranin (10(-4) M) weakly inhibited the cyclooxygenase activity as assessed by measurement of 12-hydroxy heptadecatrienoic acid (HHT) In contrast, the 12-hydroxy-eicosatetraenoic acid (12-HETE) synthesized by the 12-lipoxygenase was strongly increased by about 650%. The same effects were observed with 10(-6) M of dicranin but to a lesser extent. The main platelet hydroxylated dicranin metabolite determined by GC-MS was a 13-hydroxy derivative Platelet aggregation induced either by thrombin or by arachidonic acid or by U46619, an structural PGH2 analogue was inhibited by 10( 4) M of dicranin. PMID- 1632298 TI - Effect of BN 52256 and other mediator antagonists on ouabain-induced ventricular fibrillation in sensitized guinea-pigs and on ischemia-induced fibrillation in rats. AB - The threshold dose of ouabain necessary to induce ventricular fibrillation is decreased in sensitized guinea-pigs signalizing an enhanced arrhythmogenicity. Esculetine or WEB 2170 antagonists of histamine and PAF, respectively and especially a combination of both can increase the threshold dose of ouabain induced fibrillation demonstrating an antiarrhythmic effect. BN 52256 a substance with multi-antagonistic properties shows antiarrhythmic effect in this method, too. WEB 2170 and BN 52256 decrease the incidence of ventricular fibrillation after coronary ligation in rats. PMID- 1632299 TI - Influence of a cholesterol rich diet in rabbits on the formation of PGI2 and TXA2. AB - In the study was investigated whether the formation of prostanoids is changed in the different regions of aorta or in clotting whole blood in dependence on development of atherosclerosis. For this question New Zealand rabbits were fed for different periods with a cholesterol rich diet (0.5%). At the end of the different dietary periods the animals were killed and the following parameters estimated: blood: levels of total cholesterol, HDLcholesterol, VLDLcholesterol, cholesterol in the beta-migrating lipoprotein fraction, serum lipid peroxides, TXB2 formation capacity of clotting whole blood; aorta: surface of intima covered with fatty streaks, free and esterified cholesterol, triglycerides, collagen, formation of 6-keto-PGF1a and TXB2 by abdominal and thoracic aortas. The lipid parameter demonstrated a relatively strong correlation with the duration of cholesterol rich diet or the macroscopically detectable atherosclerosis, but the prostanoid formation remained unchanged. PMID- 1632300 TI - Increased production of platelet-derived thromboxane in patients with lupus anticoagulant. AB - The in vivo production of thromboxane A2 and prostacyclin was assessed in 31 samples from 25 patients with lupus anticoagulant and in 32 controls. The urinary excretion of 11-dehydro-thromboxane B2 (a major thromboxane metabolite of platelet origin) was very significantly increased (p less than 0.0003) in the patients contrasting with a lesser increase of urinary 2,3-dinor-6-keto prostaglandin F1 alpha reflecting the vascular production of prostacyclin (p less than 0.02). Our study shows that in patients with lupus anticoagulant, platelet activation may occur without a compensatory increment in the vascular biosynthesis of prostacyclin suggesting an increased risk for thrombosis. PMID- 1632301 TI - Eicosanoids, other fatty acid metabolites and the cardiovascular system: are the present antithrombotic approaches rational? AB - Antiplatelet +/- anticoagulant drugs are currently used as the standard treatment to prevent and treat thrombosis. While this approach is beneficial, it is not optimal. Recent evidence suggests that constituents of the vascular endothelium play an important role in regulating vessel wall thrombogenecity, thereby inhibiting thrombogenesis. These include constituents such as PGI2, tissue plasminogen activator, thrombomodulin and the lipoxygenase fatty acid metabolite derived from linoleic acid, 13-hydroxyoctadecadienoic acid (13-HODE). Consequently, new strategies have been developed to maximize the use of these agents for antithrombotic therapy. We will review these different approaches, discuss their rationale, and based upon recent experimental data, introduce an alternative approach for antithrombotic therapy which may circumvent a number of limitations and side-effect of the currently used drugs. PMID- 1632302 TI - Antiatherosclerotic properties of oral cicaprost in hypercholesterolemic rabbits. AB - The effects of the orally active prostacyclin mimetic cicaprost on morphologic and functional alterations of rabbit aorta was investigated in experimental hypercholesterolemia. Oral cicaprost resulted in a significantly reduced aortic atheromatous plaque formation and partially prevented hypercholesterolemia induced impairment of endothelium-dependent relaxations. It is concluded that long-term substitution with PGI2 may beneficially influence the progression of atherosclerosis. PMID- 1632303 TI - Oral cicaprost reduces platelet and neutrophil activation in experimental hypercholesterolemia. AB - Oral treatment of cholesterol-fed rabbits with the PGI2 mimetic cicaprost largely reduces hypercholesterolemia-induced platelet and neutrophil hyperreactivity. In addition, cicaprost prevents atherosclerosis-induced platelet desensitization for PGI2. These effects persist after cicaprost treatment is withdrawn. Since platelets and leukocytes are supposed to contribute to atherogenesis, this suggests a favourable effect of long-term oral PGI2 substitution in hypercholesterolemia. PMID- 1632304 TI - Oral cicaprost protects from hypercholesterolaemia-induced impairment of coronary vasodilation. AB - Isolated Langendorff-hearts prepared from cholesterol fed rabbits (1% cholesterol for 3 months) showed a significant impairment in endothelium-dependent relaxation after short-term infusion of bradykinin (0.05 mumol/l) and carbamoylcholine (0.1 mumol/l). Generation of the endothelial mediators nitric oxide and prostacyclin by bradykinin was enhanced in hypercholesterolemia. Cicaprost treatment (5 micrograms/kg x d) largely prevented the hypercholesterolemia-related impairment of coronary vasodilation and nitric oxide release. It is concluded that (i) impairment of endothelium-dependent relaxation in the coronary microcirculation of hypercholesterolemic rabbits is not due to diminished endothelium-dependent mediator release but rather to accelerated inactivation or reduced activity of the released mediators and that (ii) oral cicaprost beneficially influence these alterations. PMID- 1632305 TI - Effects of ciprostene on restenosis rate during therapeutic transluminal coronary angioplasty. AB - Ciprostene, a chemically stable prostacyclin analog was studied for its effects on restenosis in patients with coronary artery disease undergoing therapeutic percutaneous transluminal coronary angioplasty (PTCA). In a double-blind, randomized trial 32 patients were randomized to receive either ciprostene or the respective placebo. The infusion started intracoronarily at a rate of 40 ng/kg/min 20 min before introduction of the balloon catheter into the coronary artery. Thereafter infusion was continued intravenously for 36 hours at a rate of 120 ng/kg/min and a tapering off period until 48 hours. The quantitative analyses of the degree of coronary artery stenoses on the angiographic films before PTCA, after PTCA and after 6 month of follow-up was performed in 24 patients available. In patients receiving placebo (n = 12) coronary artery stenoses was 81 +/- 3% before PTCA and was reduced to 34 +/- 3% by angioplasty. At the 6 month follow up angiography stenoses diameter was measured as 63 +/- 8%, being not significantly different from the % stenoses before PTCA. In contrast, coronary artery stenoses in patients receiving ciprostene (n = 12) measured 83 +/- 3% before PTCA, 31 +/- 4% after PTCA and 55 +/- 9% at 6 month, being still significantly different from pre-PTCA value (P less than 0.05). When patients were characterized according to their clinical status, these differences were accounted for by patients with unstable angina receiving ciprostene. Ciprostene seems to reduce restenosis 6 month after coronary angioplasty in patients with unstable angina. The infusion rate of 40 ng/kg/min i.c. followed by 120 ng/kg/min i.v. was tolerated well, although the incidence of catheter associated bleeding was increased. PMID- 1632306 TI - Endogenous prostacyclin preserves myocardial function and endothelium-derived nitric oxide formation in myocardial ischemia. AB - Nitric oxide (NO) and prostacyclin (PGI2) release was determined in effluents of Langendorff-perfused rabbit hearts under control conditions and during reperfusion subsequent to 2 h of global, low-flow ischemia. PGI2 release (6-oxo PGF1 alpha) was significantly enhanced during early reperfusion and remained enhanced during a total time of 70 min of reperfusion. NO formation was reduced during ischemia but was substantially enhanced during reperfusion. Inhibition of endogenous PGI2 production by indomethacin resulted in severe disturbance of myocardial function and NO release. Inhibition of NO generation by L-N nitroarginine did not affect myocardial contractility. These data suggest a cardioprotective and endothelium-protective role of PGI2 in myocardial ischemia which also involves protection of NO generation. PMID- 1632307 TI - Role of prostacyclin in normal and arteriosclerotic human coronary arteries during hypoxia. AB - Human coronary arteries were taken from heart transplant patients. Arteriosclerotic arteries were more depolarized and constricted over the whole PO2 range between 535 and 0 mm Hg. During oxygen deficiency, control preparations showed a maximal hyperpolarization of delta V = 10.9 mV and a maximal relaxation of delta T = 0.466 g. Arteriosclerotic arteries, however, became hyperpolarized by merely delta V = 7.1 mV and relaxed by delta T = 0.258 g. The isometric pretension was 2 g in all investigations. Two series of experiments, one with an application of indomethacin and another one with deendothelialized blood vessels, confirmed the hypothesis that the endothelium of arteriosclerotic coronary arteries arteries, indomethacin reduced the hypoxic hyperpolarization and dilatation at 30 mm Hg PO2 but about 51%. The reduction was 26% in arteriosclerotic vessels. The complete removal of the endothelium caused a 49% (74%) restriction of dilatory vascular reactivity. The relation was quite similar for a carbogen Krebs solution (resting, control conditions). The hyperpolarizing and dilatory contribution by prostacyclin was 32% in normal and 12% in arteriosclerotic coronaries. The rest can be attributed to the basal release of the endothelial dilator EDHR. Thus, it may be concluded that, in arteriosclerotic blood vessels, PGI2 synthesis and release are predominantly diminished or its effectivity is impaired. Finally we found the ratio PGI2/EDHF in the voltage and tension changes strongly shifted to the PGI2 side with a declining oxygen concentration. This is true for normal and arteriosclerotic vessels. In accordance with the activation curve for vascular smooth muscle, the hyperpolarization leads to relaxation via a closure of Ca2+ channels. 2.5 mV hyperpolarization reduces the tension developed by half. PMID- 1632308 TI - Involvement of PAF in atherogenesis. Brief review. AB - Crucial points have been recently explored between formation, release and breakdown of PAF and atherosclerotic plaque formation. Experimental and clinical studies suggest that an autocatalytic feedback network among PAF, cytokines and growth factors contributes to atherogenesis. This novel approach to atherogenesis deserves future therapeutical importance. PMID- 1632309 TI - Regulation of the concentration of free arachidonic acid in homogenates of human platelets. AB - With the intention to study the regulation of the availability of free arachidonic acid through the enzymes of the Lands cycle, we established a model system in homogenates of human platelets. Phospholipase A2, arachidonoyl-CoA synthetase and lysophosphatidyl acyltransferase proved to be simultaneously active and a steady turnover of arachidonic acid was the consequence. EGTA suppressed the deacylating activity that acted on endogenous membrane phospholipids and prevented eicosanoid formation from previously esterified exogenous arachidonoyl-CoA. The reacylating enzymes took part in the control of eicosanoid biosynthesis by re-esterification of liberated arachidonic acid. Blockade of the reacylation by apyrase made arachidonic acid completely available for further metabolization into 12-HETE and thereby induced an increase in the eicosanoid release. PMID- 1632310 TI - Sexual dimorphism in blood pressure response to thromboxane agonist U 46619 and to endothelin. AB - The blood pressure rising effect of two vasconstrictoryacting substances (the thromboxan agonist U 46619 and the endothelium-derived peptide endothelin-1) differs in male and in female rats and this fact depends on normotensive or hypertensive levels of blood pressure. Whereas in male rats the drug effect was changed by pretreatment with aspirin, in female rats aspirin was uneffective in changing the blood pressure response to the agents. It could be suggested that the mechanism(s) for blood pressure regulation, especially the vasoconstrictor system, is different in males and females. PMID- 1632311 TI - Effect of irradiation on the prostaglandin system of human hypernephroma cells. AB - Specific PGE1-, PGE2-, PGI2-binding sites and the eicosanoid production were investigated in cultured human hypernephroma cells. Low numbers of PGE1-, PGE2- as well as PGI2-high-affinity binding sites and high levels of PG-production were found as compared to normal kidney. Treatment with acetylsalicyclic acid (ASA) significantly (p less than 0.01) increased PGE1-, PGE2- and PGI2-binding sites and inhibited PG-formation. Following irradiation, PG-receptors and eicosanoid generation were significantly (p less than 0.01) diminished, however, were insignificantly lowered in the ASA-treated group. These findings suggest that ASA may modify the radioresponse of cultured hypernephroma cells by preventing the decrease of PG-receptors induced by irradiation. PMID- 1632312 TI - Prostaglandin (PG) E1 and 13,14-dihydro (DH) PGE1 are diminishing radiation induced arterial damage. AB - Rabbit abdominal aorta was irradiated with single or repeated doses up to 10 Gy. The rabbits were killed at different time intervals after irradiation. 5 micrograms/kg x 6/hr PGE1 or its biologically active metabolite 13,14-DH-PGE1 were administered either 6 hours before or 6 hours after irradiation. The administration of both PGEs reduced radiation-induced mitotic activity (3H thymidine incorporation) and extracellular matrix [collagen-(14C-proline) and glycosaminoglycan (35-S-sulphate)]-formation as determined by means of autoradiography. The initial peak increase in vascular PGI2-synthesis was partly abolished, while the long lasting depression was less pronounced. 13,14-DH-PGE1 was only slightly less active as compared to the parent compound. Pre-radiation treatment was more effective than post-irradiation therapy. These findings suggest that both the PGs exert significant radiation-protective actions on the arterial wall. PMID- 1632313 TI - Identification of oxidatively modified lipids in atherosclerotic lesions of human aortas. AB - The oxygenated lipids of human aortas with atherosclerotic lesions were analysed by RP-, SP- and Chiral Phase-HPLC and compared with those obtained after treatment of human LDL with pure 15-lipoxygenase (LOX) of rabbit reticulocytes. The data suggest an indirect role of 15-LOX in the atherogenesis in aortas. PMID- 1632314 TI - Purification to homogeneity of an NAD dependent 11-hydroxythromboxane B2 dehydrogenase from porcine kidney. AB - A protein with NAD dependent 11-hydroxythromboxane B2 dehydrogenase activity was purified to homogeneity from porcine kidney using a simple purification procedure, involving precipitation, anion exchange chromatography (DE-52), affinity chromatography (5'-AMP-Sepharose) and gel filtration chromatography (Protein Pak 300SW). The dehydrogenase was found to have a molecular mass of 50 kDa and 42 kDa as determined by comparison with standards on SDS/PAGE and gel filtration chromatography respectively. The apparent Km and Vmax values for thromboxane B2 were 220-250 microM and 15-30 nmol min-1 mg-1 respectively. The enzyme was clearly separated from the proteins with 15-hydroxyprostaglandin dehydrogenase activity also present in the kidney. Furthermore it was found that 11-hydroxythromboxane B2 dehydrogenase did not utilize prostaglandin D2 prostaglandin E2 or prostaglandin F2 alpha as substrate, and that the enzyme did not catalyze the reverse reaction, conversion of 11-dehydrothromboxane B2 to thromboxane B2. PMID- 1632315 TI - Biosynthesis of TXB2 and 6-oxo-PGF1 alpha in the heart and other tissues under pathophysiological conditions. AB - Many organs have the capacity to form prostanoids. Under pathophysiological conditions the biosynthesis of TXB2 and 6-oxo-PGF1 alpha is markedly increased in the myocardium and the gastric mucosa. Tumor growth is linked with an enhanced prostanoid formation. Furthermore a rise of the PG content could be found in the liquor, aqueous humor and urine under diseases of the related organs. These results could be of some significance for diagnosis and therapy control. PMID- 1632316 TI - [Evaluation of complicated renal cyst: a comparison of CT and MR imaging]. AB - We report 12 cases of renal cystic lesions that could not be diagnosed preoperatively. Sonography, computed tomography (CT), magnetic resonance (MR) imaging, and angiography were performed in all cases. Angiography was not helpful in evaluating cystic lesions, because all cystic lesions were hypovascular or avascular within the cystic mass. CT was useful in depicting the fine structural abnormalities, and especially bolus-contrast CT study was useful in the differentiation of cystic renal cell carcinoma from simple renal cyst. However, there were 5 false positive cases. MR imaging is superior to CT in distinguishing a hemorrhagic cyst or multiloculated cystic mass. In conclusion, CT is currently the primary imaging modality for evaluating complicated renal cysts, and surgical exploration is warranted for the undiagnosed cystic lesion by CT. However, MR imaging also has an important role in detecting the benign complicated cyst. Therefore if complicated cyst is thought to be benign by MR imaging, parenchyma sparing surgery should be considered preoperatively. PMID- 1632317 TI - [Detection of mutant adenine phosphoribosyltransferase genes by polymerase chain reaction-single strand conformation polymorphism analysis]. AB - Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis is a rapid and sensitive method to identify point mutations in a given sequence of genomic DNA. We tried to apply the PCR-SSCP to the diagnosis of adenine phosphoribosyltransferase (APRT) deficiency, which is an autosomal recessive hereditary disease leading to 2,8-dihydroxyadenine urolithiasis. Genomic APRT genes, with or without mutations, were amplified and labeled simultaneously with 32P-dCTP by PCR. When run in a 6% polyacrylamide gel containing 10% glycerol, two types of mutant genes, APRT*Q0 and APRT*J, gave bands clearly distinct from those of the respective normal APRT genes. Since heterozygotes as well as homozygotes for these mutant APRT genes can be detected in 2 days, PCR-SSCP should be a valuable method in the diagnosis of APRT deficiency and in screening a large population for APRT mutant genes. PMID- 1632318 TI - [Clinical assessment of patients with microscopic hematuria pointed out by mass screening examination]. AB - We clinically examined 445 patients with positive urine occult blood test found by mass screening examination. Among them, 41 cases had the history of macroscopic hematuria. Urological abnormalities were observed in 169 (41.8%) of the patients with microscopic hematuria, and in 22 (53.7%) of those with a history of macroscopic hematuria. Genitourinary neoplasms were found less frequently in the patients with microscopic hematuria (1.2%) than in those with macroscopic hematuria (22%). We couldn't find a correlation between the degree of hematuria and the severity of the underlying diseases. Hematuria is often thought to appear intermittently, and urinalyses of the patients with so-called significant disease may not be found at the first visit. PMID- 1632319 TI - [Indiana continent urinary reservoir: technical modifications and late complications]. AB - From October, 1987 through September, 1991, 39 patients underwent construction of Indiana pouch for cutaneous urinary diversion. There were 35 men and 4 women, and their ages ranged from 38 to 77 years (a mean age of 62 years). After the first 8 cases, Indiana pouch was constructed with several modifications which included complete detubularization of the cecum, construction of the pouch augmented with U-shaped ileal patch, and the use of stapled plication. There was no major early complication related to the pouch but one postoperative death of blood transfusion related graft versus host disease. End results were evaluated in 37 patients who were followed for 3 to 49 months. Late complications related to urinary reservoir occurred in 8 patients. The early two patients experienced pouch deformity due to incomplete detubularization of the colonic segment. Two patients had difficult catheterization due to a dilatation of the plicated ileum. One patient had metabolic acidosis requiring hospitalization. Patients perform self-catheterization 4-5 times during the day and 0-2 times at night for volumes ranging from 300 to 1,000 cc. Of 37 patients 34 achieved acceptable urinary continence and one had significant leakage requiring cutaneous bag. The remaining two patients suffered mild nocturnal incontinence. Follow up examination with excretory urography showed no upper urinary tract obstruction except one with unilateral hydronephrosis due to ureteroanastomotic stricture. Reservoirgraphy showed no reflux into the upper urinary tract in all the follow up cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632320 TI - [The clinical usefulness of flow cytometric DNA analysis in prostatic cancer]. AB - Flow cytometry was used to measure the DNA content in archival paraffin-embedded prostatic cancer specimens from 54 patients with known outcomes. The specimens were obtained by transurethral resection of the prostate. DNA ploidy as a predictor of prognosis was compared with histological grade and clinical stage. Although no significant correlation between histological grade or clinical stage and ploidy pattern was demonstrated, an increased percentage of DNA aneuploid tumors was seen in higher histological grade and in advanced clinical stage. The survival rate calculated by Kaplan-Meier analysis showed that DNA ploidy pattern was a more reliable indicator to predict survival probability than histological grade or clinical stage. All patients with a near diploid pattern (11 patients) survived more than 5 years, whereas all those with an aneuploid pattern (21 patients) died within 3.5 years. Of 22 patients with a tetraploid pattern, 15 died of tumor progression within 5 years. The remaining 7 patients with favorable outcome had a relatively lower proliferation index (less than 65) in DNA histogram and none of them suffered from stage D disease. In conclusion, the results from this retrospective study suggest that flow cytometric DNA analysis in prostatic cancer would be useful as a means of providing prognostic information. PMID- 1632321 TI - [Clinical and pathological study of 152 cases of prostatic cancer]. AB - A total of 152 prostatic cancer patients who underwent mainly hormone therapy was conducted. Our histological grading system combined with structure atypsim--SAT and nuclear anaplasia--NAN allowed for more accurate prognosis of prostatic cancer patients. The prognosis of G3 patients was obviously poor. The over-all 5 year survival rate for prostatic cancer patients with G1, G2 and G3 was 80%, 57% and 17%, respectively. The 5-year reactivation rate for patients with G1, G2 and G3 was 14%, 32% and 87%, respectively. The period for reactivation after initial hormone therapy for prostatic cancer patients with G1, G2 and G3 was 11.4, 10.0 and 3.2 years, respectively. Further improvements in survival for the patients with G3 prostatic cancer will require the development of effective systemic chemotherapy and the re-consideration of appropriate use of hormone therapy. PMID- 1632322 TI - [Adrenal pseudocyst: a case report]. AB - A 23-year-old man presented with high fever and left abdominal pain. Ultrasonography, CT scan and angiography visualized a left adrenal cyst. Cyst fluid obtained preoperatively by percutaneous needle puncture under ultrasonographic guidance was purulent, and had a higher level of aldosterone, and lower level of amylase than the plasma. These findings suggested that this cyst originated from the adrenal gland. Histopathological examination of the surgically removed specimen confirmed the adrenal pseudocyst. PMID- 1632323 TI - [Adrenal myelolipoma associated with Cushing's syndrome: a case report]. AB - A 42-year-old woman was referred to our hospital for evaluation of severe hypertension. A right adrenal tumor was revealed by CT scan, and the elevation of cortisol and u-17OHCS was found. We made a diagnosis of adrenal adenoma with Cushing's syndrome and performed right adrenalectomy. However, a small myelolipoma (1.5 mm in diameter) was found beside the cortical adenoma by histopathological examination. Adrenal myelolipoma is not a rare disease now, because it is easily-detected as an incidental by CT scan. The present case of adrenal myelolipoma, however, is interesting and uncommon in its connection with functioning cortical adenoma. Only 3 cases have been previously reported so far in English and Japanese publications. We discuss the etiology of adrenal myelolipoma, and suggest that myelolipoma would develop in the course of regressive or necrotic degeneration of cortical cells by hormonal disorders, stress, circulatory disturbance or other unknown factors. PMID- 1632324 TI - [A case of retrovesical fibrosarcoma with severe hypoglycemia]. AB - We report a case of retrovesical fibrosarcoma with severe hypoglycemia. A 67-year old man was admitted to our hospital with second recurrence of the retrovesical tumor with hypoglycemia. The episodes of hypoglycemia were accompanied by the advance of tumor size. Complete tumor resection with total cystectomy was performed on December 21, 1989, and the tumor was diagnosed histopathologically as fibrosarcoma. Soon after removal of the tumor, hypoglycemia disappeared and the patient has been well without local recurrence or distant metastasis for more than 20 months. PMID- 1632325 TI - [Simultaneous double malignant tumors on functional solitary kidney: a case report]. AB - A case of simultaneous double cancer on functional solitary kidney is reported. A 72-year-old man was admitted to the Department of Internal Medicine with angina, hypertension and diabetes mellitus. After treatment involving percutaneous transluminal coronary angioplasty, he was sent to the Department of Urology to check the microhematuria. Cystoscopy showed normal interior of urinary bladder. Drip infusion pyelography and computed tomography demonstrated a tumor mass on the upper pole of the right kidney and atrophic left kidney. Preoperative diagnosis was right renal cell carcinoma. However, an additional pelvic tumor was found during surgery, and a partial nephrectomy was performed. Histologic examination confirmed the presence of 2 separate and distinct malignant entities: a renal cell carcinoma and a non-invasive transitional cell carcinoma. Postoperative recovery has been uneventful and without hemodialysis for 16 months. This is the 19th case of simultaneous occurrence of renal cell carcinoma and transitional cell carcinoma in the same kidney and the 1st case in the patient with a functional solitary kidney in the Japanese literature. PMID- 1632327 TI - [A case of renal cell carcinoma in a horseshoe kidney]. AB - We report a 68-year-old man with renal cell carcinoma in a horseshoe kidney. Abdominal computed tomography revealed a left renal tumor in a horseshoe kidney, and we carried out left radical nephrectomy. Histopathological diagnosis was renal cell carcinoma. Only 19 cases of renal cell carcinoma in a horseshoe kidney have been reported in Japan, and our case was the 20th. PMID- 1632326 TI - [A case of multilocular renal cell carcinoma]. AB - Herein we report case of multilocular cyst of the right kidney complicated with clear cell type renal cell carcinoma. The chief complaint of the 51-year-old male patient was macroscopic hematuria. He underwent radical nephrectomy and was administered postoperative adjuvant chemotherapy with alpha-interferon. No recurrence was found 18 months after operation. Pathogenesis of multilocular cyst of the kidney and the mechanism of malignant transformation are discussed. PMID- 1632328 TI - Primary localized amyloidosis of the renal pelvis coexisting with transitional cell carcinoma: a case report. AB - Primary localized amyloidosis of renal pelvis is very rare, and only 12 cases have been reported. More than half of the reported cases were treated by nephrectomy, and the preoperative diagnosis could not be made correctly because of its resemblance to renal pelvic tumor. The ureteroscopy is a useful diagnostic means in such a condition. This case is unusual in that a papillary transitional cell carcinoma was present coincidentally. PMID- 1632329 TI - [A case of infected caliceal diverticulum]. AB - A 60-year-old woman was admitted to our clinic with the chief complaint of high fever. Antibiotic therapy had produced no improvement in another hospital and she was referred to our hospital for further examination and treatment. Intravenous pyelography showed left non visualized kidney and a stone shadow in left ureter. Computed tomography showed a cystic lesion, 9 x 9 x 8 cm, in the upper pole of the left kidney. We punctured and drained 400 cc of turbid yellowish fluid by a transcutaneous route. The nephrostogram clearly showed a communication with infundibulum. A diagnosis of infected caliceal diverticulum was made. Further examination demonstrated no function of left kidney and we performed nephrectomy. She has reported no symptoms for 6 months after the operation. PMID- 1632330 TI - [Primary ureteral tumor in the residual ureter: a report of two cases]. AB - Two cases of primary ureteral tumor in the residual ureter are reported. One was in a 40-year-old woman who had undergone simple nephrectomy for renal tuberculosis 6 years earlier. The other was in a 59-year-old man 11 years after ureterostomy for hydronephrosis. They presented with hematuria. Cystoscopic examination revealed a ureteral tumor out of the residual ureteral orifice. Computed tomographic scan showed a perivesical mass attached to the urinary bladder. It is useful for examination of ureteral stump's condition. We performed ureterectomy. The pathological study revealed the former high grade transitional cell carcinoma with squamous cell carcinoma and lymph nodes metastasis and the latter low grade transitional cell carcinoma. They have been free of disease for 5.5 years and 1.75 years, respectively. These cases are the nine and tenth reports of primary ureteral tumor of the ureteral stump in the Japanese literature. PMID- 1632331 TI - [Primary carcinoma in diverticulum of the bladder: a report of three cases]. AB - The first case was in a 48-year-old man admitted with a chief complaint of macroscopic hematuria and sense of residual urine. A tumor in the diverticulum of the bladder was detected by cystoscopy, computed tomography (CT) and magnetic resonance imaging (MRI). We made the diagnosis of an invasive tumor in the diverticulum of the bladder. Total cystourethrectomy and ileal conduit diversion was performed. Histopathological finding was transitional cell carcinoma including squamous cell carcinoma. Adjuvant chemotherapy was performed. No recurrence and metastasis has been recognized for 12 months. The second case was a 56-year-old man having an intradiverticular tumor diagnosed by cystoscopy, CT, and MRI. Total cystectomy and ileal conduit diversion was performed. Histopathological findings was squamous cell carcinoma. No recurrence has been recognized for 8 months. The last case was an 81-year-old man. The patient had the complication of a primary progressive squamous cell carcinoma of the skin. Transurethral resection of diverticular tumor was performed under the diagnosis of superficial tumor. Histopathological findings revealed transitional cell carcinoma. One hundred and sixty one cases of tumor in the diverticulum of the bladder were reviewed. Importance of aggressive treatment including total cystectomy was emphasized. PMID- 1632333 TI - [Effects of Tsumura Chorei-to and Tsumura Chorei-to-go-shimotsu-to on patients with urethral syndrome]. AB - Tsumura Chorei-to or Tsumura Chorei-to-go-shimotsu-to, was administered to 71 female patients with urethral syndrome 2.5 g three times a day for four weeks. Total efficacy rate of Tsumura Chorei-to in 34 cases was 71%. Tsumura Chorei-to was effective against pollakisuria, miction pain or discomfort, sense of residual urine and lower abdominal discomfort. Total efficacy rate of Tsumura Chorei-to-go shimotsu-to in 37 cases was 57%. Tsumura Chorei-to-go-shimotsu-to was effective against dysuria, sense of residual urine and lower abdominal discomfort. Uutoward effect rates of Tsumura Chorei-to and Tsumura Chorei-to-go-shimotsu-to were 6% and 14%, respectively. Many of the untoward effects of these two drugs were epigastral discomfort. These two drugs are thought to be effective on patients with urethral syndrome. PMID- 1632332 TI - [Repair of skin defect after extensive resection for penile cancer: report of two cases, and clinical observation of patients with penile cancer at Mie University hospital]. AB - Case 1: A 48-year-old male with stage 4 penile cancer is reported. We used peplomycin (PEP) and cisplatinum (CDDP) for preoperative chemotherapy. Chemotherapy was effective. Radical surgery with bilateral inguinal lymphadenectomy was done and skin defect was covered with a skin flap. Case 2: A 61-year-old male with stage 4 penile cancer underwent radical surgery after modified MBD therapy with methotrexate (MTX), PEP and CDDP. Emasculation with skin resection and inguinal and pelvic lymphadenectomy were performed. The skin defect was deep and wide. It was covered with a glacilis myocutaneous skin flap. Distal end of the flap became necrotic. It was covered with tensor fascia lata myocutaneous flap. Seventeen patients with penile cancer were treated between 1972 and 1990 at Mie University Hospital. Nine patients were in stage 1, 4 stage 2, 1 stage 3, 3 stage 4. Treatment consisted of surgery (3), surgery+chemotherapy (10), surgery+chemotherapy+irradiation (2), chemotherapy+irradiation (1), and surgery+irradiation(1). Cancer death was observed in 2 cases (stage 2), 2 patients died of other diseases, 10 are alive, and 3 patients were lost to follow up. PMID- 1632334 TI - [Clinical study of levofloxacin (DR-3355) on uro-genital infections--with special reference to usefulness for chronic prostatitis]. AB - The clinical usefulness of levofloxacin, an optical active isomer of ofloxacin, was investigated on uro-genital infections. Patients who were treated with the drug included 2 with complicated urinary tract infections (UTI), 29 with chronic prostatitis and 3 with chronic non-chlamydial epididymitis. Levofloxacin was given to each patient at a dose of 300 mg or 400 mg a day for 7-14 days (average 12.0 +/- 0.5 days). In 2 cases of chronic UTI, infected by P. aeruginosa in one case and P. stutzeri in another case, the isolates were eradicated, and the clinical efficacy was moderate or excellent. For evaluating the effectiveness on chronic prostatitis, the patients were divided into 2 groups; group I (G-I) was chronic bacterial (number of isolates including GNR or E. faecalis, greater than or equal to 10(4) ml) and group II (G-II) was chronic non-bacterial prostatitis (number of isolates including GPC less than or equal to 10(3)/ml). A complete bacteriological response was obtained in all 7 cases, classified in G-I, but in 20 of the 27 isolates, (74.1%) in G-II. In 3 cases of chronic non-chlamydial epididymitis, the response was moderate. In safety profile, there were slight elevations in the laboratory values of glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) in one case, and that of GOT in another case. As for side effects, a 69-year-old male complained of dizziness, and anorexia after 10 days on the drug, but recovered 2 days after discontinuance of the drug. PMID- 1632335 TI - Stress fractures: current concepts. AB - Stress fractures are extremely common lesions that occur in specific areas and are related to specific activities. They are caused by increased muscular activity on bones that are not yet ready to take the increased pull of the involved muscles. The insufficiency type of stress fractures found in patients with bone of diminished mineral content is being recognized more often as increasing numbers of middle-aged and elderly persons are becoming more physically active. A variety of imaging studies can be used to diagnose stress fractures. Radionuclide bone scanning and MR imaging often show abnormalities early in the course of the injury. However, when radiographs appear normal, findings on scintigrams may be more suggestive of the proper diagnosis. In patients with suspected stress injury, radiographs should be obtained a second time, 1-2 weeks after the initial study. Biopsy should be avoided until evidence is clear-cut that the lesion has not changed over a short time. PMID- 1632336 TI - Infertility in women: diagnostic evaluation with hysterosalpingography and other imaging techniques. AB - This article examines the current roles of hysterosalpingography and other imaging studies used in diagnostic assessment and treatment of infertility in women. The advantages and limitations of hysterosalpingography, transabdominal or transvaginal sonography, and MR imaging in detecting abnormalities of the uterus (congenital anomalies, intrauterine adhesions, myometrial and endometrial derangements) and tubal and peritubal disease are presented. The use of sonography to evaluate cyclical endometrial changes, to assess development of the follicle and corpus luteum, to determine whether ovulation has occurred, and to detect dysfunctional ovulatory dynamics is described, as is the role of this technique in improving the prognostic value of the postcoital test for assessing the quality of cervical mucus. With the development and availability of newer and improved methods for the treatment of infertility disorders in women, comprehensive and detailed evaluation to determine the precise underlying cause or causes of the infertility is important to allow formulation of the most appropriate therapeutic plan. With careful and thorough assessment, the cause of infertility can be identified in 90-95% of couples evaluated. PMID- 1632337 TI - Fetching the doctor. PMID- 1632338 TI - CT evidence for the "osseous pinch" mechanism of traumatic aortic injury. AB - OBJECTIVE: Our prior experiments suggested that traumatic laceration of the aorta induced by rapid deceleration results from pinching of the aorta between the spine and the anterior bony complex (manubrium, clavicle, and first rib). This study examines that hypothesis with in vivo CT data. MATERIALS AND METHODS: In 22 patients with angiographically and surgically proved lacerations of the proximal descending aorta, chest CT scans were obtained before (18) or after (four) surgical repair. The point of impact of the anterior bony complex with the anterior surface of the thoracic spine during compression of the thorax was predicted by simulated rotation of the first rib based on calculations made from the CT scans. RESULTS: In all 22 patients, the projected site of impact of the anterior bony complex with the spine corresponded to the actual injured aortic segment as determined with angiography. CONCLUSION: Our data further support the proposed "osseous pinch" mechanism of injury to explain traumatic tears of the aorta. PMID- 1632339 TI - Inverted papilloma. PMID- 1632340 TI - Intrathoracic neurogenic tumors: MR-pathologic correlation. AB - An MR-pathologic correlation of nine intrathoracic neurogenic tumors (three neurofibromas, four schwannomas, and two ganglioneuromas) was performed to characterize their MR appearances. The three types of intrathoracic neurogenic tumor were found to have characteristic appearances on MR images that should be helpful when establishing the differential diagnosis of posterior mediastinal tumors. The MR and histologic features of these tumors are illustrated and described in this essay. PMID- 1632341 TI - Transesophageal echocardiography for the evaluation of atherosclerosis of the thoracic aorta. PMID- 1632342 TI - Interval carcinomas in the Malmo Mammographic Screening Trial: radiographic appearance and prognostic considerations. AB - OBJECTIVE: Interval carcinoma is the term used to describe malignant breast tumors that are detected in the intervals between mammographic screenings. These tumors are important because they contribute significantly to breast cancer mortality in the screened population. MATERIALS AND METHODS: Two radiologists retrospectively reviewed the mammograms of the 96 interval carcinomas (17% of all malignant neoplasms in the screened group) that were detected during the 10-year Malmo Mammographic Screening Trial in Malmo, Sweden (average time between screenings, 21 months), including one sarcoma, 75 invasive carcinomas, and 20 noninvasive carcinomas. We recorded the interval between screening and detection, and noted the tumor's appearance on the prior screening mammogram and at the time of diagnosis; these data were correlated with histologic tumor type and the patients' mortality. The doubling time for tumor volume of the invasive carcinomas was estimated. RESULTS: Excluding the sarcoma, 72 carcinomas (75%) were detected within 18 months of screening. Retrospective review of the available preceding screening mammograms (94 cases) indicated that 10 tumors were missed (observer's error), 63 studies showed no tumor (true interval carcinomas), and 21 studies showed subtle signs of malignancy, mostly nonspecific densities or asymmetries (unrecognized sign). Of 66 invasive carcinomas in which doubling times for tumor volume could be calculated, 27 (41%) had doubling times of less than 100 days. At the end of the study, 20 of the 96 patients had died of breast cancer. CONCLUSION: Interval carcinomas in this series were dominated by comedo, medullary, and mucinous carcinomas that often had a nonspecific appearance (when present) on prior screening mammograms. The interval carcinomas also contained a subset of rapidly growing tumors with a grave prognosis. PMID- 1632343 TI - Evaluation of mammographic image quality: pilot study comparing five methods. AB - A radiograph is considered of high quality when it allows a radiologist to identify abnormalities with high sensitivity and specificity. Although many methods for assessing image quality have been devised, it is not clear which is most meaningful or how well these methods correlate with one another. A pilot study was undertaken to compare five methods of evaluating mammographic image quality. Each of the methods was used to form separate rankings of 11 mammographic system configurations. In two of the methods, observers (three radiologists and three physicists) subjectively ranked the "image quality" of radiographs of phantoms obtained with each configuration. The third method ranked the systems according to contrast as measured densitometrically with an aluminum step wedge, and the fourth, in terms of lowest to highest mean glandular radiation doses to the breast. In the final method, observers based their rankings on mammograms of patients. The intra- and interobserver variabilities of each ranking method were assessed, as well as the correlations between methods, by using standard nonparametric statistical tests. Intraobserver consistency was high with any of the image quality ranking methods; however, image quality rankings based on either of the two phantoms provided better agreement among observers than did rankings based on images of patients. Surprisingly, no significant degree of correlation was found between any two image quality evaluation methods. Our work may have two implications for the American College of Radiology Mammography Accreditation Program: (1) small variations in phantom scores do not necessarily correlate with subjective variation in image quality in radiographs of patients, and (2) when small numbers of radiographs are used, the assessment of the quality of mammograms of patients may vary considerably among radiologists. PMID- 1632344 TI - Duodenal neoplasms: predictive value of CT for determining malignancy and tumor resectability. AB - CT examinations of 25 patients with proved primary or metastatic duodenal neoplasms were retrospectively reviewed to determine if morphologic features seen on CT scans could be used to predict the benign or malignant nature of these neoplasms and to assess the effectiveness of using CT findings to predict tumor resectability. We studied 19 malignant and six benign tumors. Histologic proof was obtained by means of surgery in 20 patients and by endoscopic biopsy in five. CT features of tumor morphology were assessed in the 22 cases in which a duodenal tumor was seen on CT. These features included central necrosis, ulceration or excavation, and the location of the tumor with respect to the bowel wall. The specific morphologic features used to predict that a tumor was malignant included the presence of an exophytic or intramural mass, central necrosis, and ulceration. The only criterion used to predict that a tumor was benign was that the mass be entirely intraluminal. Whenever vascular encasement, invasion of contiguous organs other than the head of the pancreas, distant lymphadenopathy, or metastases were present, the tumor was predicted to be unresectable for cure. With the exception of three benign smooth muscle tumors, all tumors with one or more CT morphologic features indicative of a malignant neoplasm were malignant (n = 16). Three of four intraluminal masses were benign. In three cases of polypoid tumors smaller than 2 cm, a duodenal tumor was not seen on CT. Whenever extraduodenal disease was found (15 cases), the neoplasms were malignant. In the 22 cases in which a tumor was detected on CT, the sensitivity of using the presence of one or more morphologic features associated with a malignant neoplasm as a predictor was 94%; the specificity was 50%, and the accuracy was 82%. If the presence of any morphologic feature indicative of a malignant neoplasm was combined with the presence of any finding of extraduodenal disease, CT was 100% sensitive and 86% accurate for predicting that the tumor was malignant. CT appears to be reliable for predicting duodenal tumor resectability. On the basis of CT findings, 10 tumors were correctly predicted as being unresectable for cure, and 12 were predicted as being resectable; no surgery was performed in the remaining three cases. In conclusion, evaluation of the morphologic features of duodenal neoplasms is a sensitive, but nonspecific, method for predicting that a tumor is malignant.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1632345 TI - CT findings in patients with small-bowel transplants. AB - Orthotopic small-bowel transplantation procedures are being performed increasingly often worldwide. CT plays an important role in both the preoperative assessment and the postoperative care of these patients. This pictorial essay serves to acquaint radiologists with the CT findings related to small-bowel transplantation. PMID- 1632346 TI - Persistence of portosystemic collaterals and splenomegaly on CT after orthotopic liver transplantation. AB - OBJECTIVE: The appearances of portosystemic collaterals and splenomegaly on CT before and after liver transplantation were evaluated. MATERIALS AND METHODS: The records of 54 patients undergoing liver transplantation during a 2.5-year period were reviewed retrospectively. Twenty-five of these patients, in whom both a preoperative abdominal CT scan and a follow-up CT scan at least 1 year after transplantation had been obtained, were clinically well and had had no significant episodes of rejection, severe recurrent hepatitis, or other complication at the time of study. A total of 94 abdominal CT scans in these patients were reviewed to assess changes in portosystemic collaterals and splenic volume. RESULTS: At 6 months after transplantation, portosystemic collaterals at one or more sites were seen in 14 (74%) of the 19 patients scanned at this time in whom collaterals had been seen on CT preoperatively. At 1 year after transplantation, splenic hilar collaterals persisted in 64% of patients, splenocolic ligament collaterals in 50%, retroperitoneal collaterals in 38%, and peripancreatic collaterals in 38% of patients with preoperative varices at these sites who were examined with CT at this interval. Splenic hilar, coronary, and retroperitoneal collaterals were found to persist for up to 4 years after transplantation in the single patient examined at that time. Splenic volume decreased in 94% of patients examined after transplantation, with a mean reduction of 60 +/- 19%. However, the spleen remained significantly enlarged in 56% of patients. CONCLUSION: We conclude that portosystemic collaterals and splenomegaly frequently persist after liver transplantation, but that this finding need not indicate recurrence of hepatic disease or other posttransplantation complications. PMID- 1632347 TI - Calcifications in the portal venous system: comparison of plain films, sonography, and CT. AB - We describe 10 patients with long-standing portal hypertension and calcifications in the splenoportal and mesenteric venous systems or collateral vessels. The patients were examined with abdominal plain films (n = 10), sonography (n = 10), and CT (n = 9). Calcium was seen on CT scans in nine cases, on sonograms in seven, and on abdominal plain films in five. Calcifications appeared to be located in the wall of the vein in all cases. Sites of detection included the main portal, splenic, superior mesenteric, coronary, and peripancreatic veins. CT was more sensitive than sonography, and both were more sensitive than plain films, in showing portal venous calcification. Detection of such calcifications may influence surgical or percutaneous therapy of portal hypertension. PMID- 1632348 TI - Abnormalities of the gallbladder after extracorporeal shock-wave lithotripsy: imaging findings. AB - To qualify for treatment with biliary extracorporeal shock-wave lithotripsy (ESWL), patients must have sonograms that show gallstones and oral cholecystograms (OCGs) that show normal opacification (indicating normal function) of the gallbladder. We have noted that sonograms and OCGs made 6 weeks to 6 months after ESWL sometimes show abnormalities that were not visible on these images before ESWL. In these cases, the gallbladder appears contracted on sonograms and is poorly visualized on OCGs. To determine how often this occurs and to study its significance, we analyzed the posttreatment sonograms and OCGs in 174 patients who underwent ESWL. After ESWL, sonograms showed a contracted gallbladder and OCGs showed poor function in 25 (14%) of the 174 patients. One patient (4%) was lost to follow-up. In 17 (68%) of the 25 patients, the abnormalities were transient (findings on sonograms and OCGs returned to normal by 12 months after ESWL). In the other seven patients (28%), the abnormalities persisted (all seven subsequently had a cholecystectomy); this is a cholecystectomy rate twice that in the patients with normal findings on sonograms and OCGs after ESWL (20/149 or 13%). All 25 patients with abnormalities after ESWL had gallstone fragments at 6 weeks, as did 146 of the 149 patients with normal-appearing gallbladders after ESWL. When these abnormalities persist (in approximately one third of patients), cholecystectomy is often required. The cause of the abnormalities is unknown, although chronic cholecystitis, a process that is not detectable by pre-ESWL imaging techniques, seems likely. PMID- 1632349 TI - Disappearing "gallstones": biliary pseudolithiasis complicating ceftriaxone therapy. PMID- 1632350 TI - Splenosis: superparamagnetic iron oxide-enhanced MR imaging. PMID- 1632352 TI - Use of transperineal hydrosonovaginography to show an incomplete vaginal septum. PMID- 1632351 TI - The seminal tract in patients with ejaculatory dysfunction: MR imaging with an endorectal surface coil. AB - Twenty-six patients with signs and symptoms of ejaculatory dysfunction (hemospermia, hypospermia, oligospermia, or painful ejaculation) were examined with high-resolution MR imaging with an endorectal surface coil. Findings were abnormal in 15 patients. Abnormalities detected included four cases of mullerian cysts, three cases of wolffian cysts, one case of anaplastic prostatic carcinoma, and various noncystic abnormalities of the seminal vesicles and ejaculatory ducts, including ejaculatory duct obstruction and seminal vesiculitis. In all cases, depiction of both the normal and abnormal anatomy of the entire seminal tract, including the vas deferens, seminal vesicles, and ejaculatory ducts, was excellent. This depiction of the detailed anatomy of the prostatic cysts made it possible to suggest specific diagnoses. Our results show the value of MR imaging with an endorectal surface coil in the examination of patients with ejaculatory dysfunction. PMID- 1632353 TI - Radiologic findings of diseases involving the maxilla and mandible. AB - The purpose of this pictorial essay is to illustrate the radiologic appearances of diseases involving the maxilla and mandible. The high prevalence of dental disease results in inflammatory, infectious, and reactive processes that must be distinguished from more serious conditions with similar radiologic features. Because of their association with odontogenic tissues, lesions of the maxilla and mandible may have radiologic findings not seen in other bones. Furthermore, nonodontogenic cysts and tumors that occur elsewhere in the skeleton may exhibit unique radiologic characteristics when associated with teeth. This pictorial essay presents the radiologic characteristics of inflammatory lesions, developmental abnormalities, fibroosseous lesions, benign cysts and tumors, and malignant lesions of the maxilla and mandible. PMID- 1632354 TI - Width of the articular cartilage of the hip: quantification by using fat suppression spin-echo MR imaging in cadavers. AB - OBJECTIVE: Use of MR imaging to measure the width of the articular cartilage has not been thoroughly investigated. The value of a selective fat-suppression spin echo sequence in the quantitative assessment of articular cartilage of the hip was studied in cadavers. MATERIALS AND METHODS: Sagittal and coronal images were acquired in 10 cadaveric hips (age range at time of death, 62-81 years). On the coronal and sagittal MR images that were closest to the center of the femoral head, marks were placed every 30 degrees, with the midpoint of the femoral head used as a reference. Cartilage thickness was measured in 123 resulting locations. Sixty-three positions included both femoral and acetabular cartilages, and 60 positions included femoral cartilage without an acetabular counterpart. The findings were compared with corresponding anatomic sections. RESULTS: For the 60 locations containing only femoral cartilage, significant correlation between MR and anatomic sections was found (Pearson correlation coefficient = .34, p = .0089). Of the 63 locations containing both femoral and acetabular cartilages, the two cartilage layers could be differentiated on the MR images in 50 locations. In these 50, the MR and anatomic measurements of the femoral cartilage correlated significant (r = .58, p less than or equal to .0001). Measurements of the acetabular cartilage in these 50 locations yielded no significant correlation (r = .25, p = .08). When the entire cartilage (femoral plus acetabular) was measured in all 63 locations, the correlation between MR and anatomic measurements was .29 (p = .02). The correlation coefficients obtained in this investigation indicate considerable scattering of the data. CONCLUSION: Our results show that measurements of articular cartilage thickness of the hip on fat suppression spin-echo MR images are not sufficiently accurate to be of clinical value. PMID- 1632355 TI - The cruciate ligaments of the knee: correlation between MR appearance and gross and histologic findings in cadaveric specimens. AB - OBJECTIVE: Using anatomic and histologic correlation, we investigated the reasons for differences in the MR signal intensity between the normal anterior and posterior cruciate ligaments and for the focally increased signal intensity within these ligaments occasionally found in elderly patients. MATERIALS AND METHODS: The MR images of 18 anterior and 20 posterior cruciate ligaments obtained from cadavers (age at death, 56-88 years old; mean, 74 years) were evaluated blindly. Their overall signal intensity and focal regions of increased signal were noted. The findings then were correlated with corresponding anatomic and histologic sections. RESULTS: The anterior cruciate ligament had greater signal intensity than did the posterior cruciate ligament in 15 of 18 knees and had comparable signal intensity in three knees. No histologic basis to explain the different MR appearances of the anterior and posterior cruciate ligaments was found. Rather, differences in macroscopic anatomy appeared to be the best explanation. In the posterior cruciate ligament, the fibers were parallel, whereas they were diverging and twisted in the anterior cruciate ligament, causing volume-averaging artifacts. A focal area of signal increase was found in 29 of the 38 ligaments. In 17 of these 29 ligaments, mucoid and/or eosinophilic degeneration was found that appeared to have caused the focal MR signal change. In nine ligaments without focally increased signal on the MR images, only one had histologic evidence of degeneration. The predictive value of an abnormal finding on MR was 59%, and the predictive value of a normal finding on MR was 89%. The relationship between increased signal on MR and histologic degeneration was statistically significant (chi 2 test, p = .0126). CONCLUSION: The differences in the MR appearances of the anterior and posterior cruciate ligaments probably are due to differences in gross architecture. Increased MR signal within the cruciate ligaments occurring in elderly patients often can be attributed to degenerative changes. PMID- 1632356 TI - Knee effusion: normal distribution of fluid. AB - Although visualization of articular fluid on MR images of the knee is common, no specific MR criteria that enable assessment of the quantity of the effusion have been established. We performed MR of three cadaveric knee specimens after the instillation of increasingly large volumes of fluid and studied the distribution of the fluid. When 4 ml of fluid was injected, the anteroposterior diameter of the suprapatellar recess was 4 mm on midline sagittal MR images and 10.0-12.5 mm on lateral sagittal MR images, corresponding to the usual routine radiographic criteria for a knee effusion. PMID- 1632357 TI - Cerebral angiography and Egas Moniz. PMID- 1632358 TI - Value of acute-phase angiography in the detection of vascular injuries caused by gunshot wounds to the head: analysis of 12 cases. AB - A study of the angiographic findings in consecutive civilian patients with cranial gunshot wounds examined in the acute stage has not been done. Most prior clinical studies have evaluated the findings in survivors in the subacute or chronic stages and have often been of war-time casualties. We determined the clinicoradiologic features of six cases of posttraumatic intracranial aneurysm, vascular occlusion, or arteriovenous fistula caused by penetrating missiles among 12 civilian patients who were examined in the acute posttraumatic stage (within 48 hr of injury) during a 1-year period. Three internal carotid/vertebral artery aneurysms, one external carotid artery aneurysm, one combined aneurysm/arteriovenous fistula of the vertebrobasilar circulation, and one cerebral venous occlusion were identified. The 50% overall prevalence of major vascular lesions in this series of civilian patients with penetrating missile injuries examined in the acute stage suggests these injuries are more common than previously suspected. It may indicate that selective cerebral angiography should be considered in the evaluation of the cranial vascular system of such persons. PMID- 1632359 TI - MR angiography of the head and neck: value of two-dimensional phase-contrast projection technique. AB - MR angiography is commonly performed by using two- and three-dimensional time-of flight and three-dimensional phase-contrast techniques. These procedures require long examination times and processing of imaging data by computing maximum intensity projections. Two-dimensional phase-contrast projection angiography has neither of these disadvantages. We analyzed the value of this technique for head and neck MR angiography in 84 patients and 15 control subjects. Patients were examined to resolve specific clinical questions such as the presence of arteriovenous malformations (20 cases), patency of carotid and vertebral arteries (35 cases), patency of the superior sagittal sinus (14 cases), patency of saphenous vein bypass grafts (11 cases), and vascularity of masses (four cases). Conventional angiograms were available for correlation in 22 patients. Two dimensional phase-contrast projection angiograms were generated by using a gradient-recalled-echo sequence sensitized to flow with the use of flow-encoding gradients. Projection MR angiograms were obtained in approximately 3.5 min by combining images obtained with flow-encoding gradients applied along the axes defining the image plane. MR angiograms were subjectively evaluated by three observers without reference to routine MR images or conventional angiograms. High quality studies were obtained in 93% of control subjects and 90% of patients examined. The findings based on phase-contrast angiography were confirmed with conventional angiography in 21 of 22 patients for whom conventional angiograms were available. Evaluation of vascular grafts and of the patency of major cranial vessels was easily done with two-dimensional phase-contrast angiography and was useful in postoperative follow-up examinations. We also advocate its use for superior sagittal sinus thrombosis and follow-up examinations in patients with arteriovenous malformations. PMID- 1632360 TI - MR imaging of the pituitary stalk: size, shape, and enhancement pattern. AB - The size, shape, signal intensity, and enhancement pattern of the normal pituitary stalk were determined retrospectively by review of MR images of 58 patients. The pituitary stalk was measured at the level of the optic chiasm and at its insertion on the pituitary gland. The contour of the stalk was smoothly tapering, measuring 3.25 +/- 0.56 mm in transverse diameter at the optic chiasm and 1.91 +/- 0.40 mm at its pituitary insertion. The signal intensity of the pituitary stalk on unenhanced T1-weighted images was less than that of the neurohypophysis in all cases and less than that of the optic chiasm in 84% of the cases. After the administration of contrast material, enhancement of the pituitary stalk occurred in all cases. A central area of nonenhancement in an otherwise uniformly enhancing stalk was variably present, depending on the size of the infundibular recess. Our study defines the size, contour, and MR signal characteristics of the normal pituitary stalk. These criteria can be used to distinguish the normal from the abnormal stalk. PMID- 1632361 TI - Hypertensive encephalopathy: findings on CT, MR imaging, and SPECT imaging in 14 cases. AB - Hypertensive encephalopathy is a syndrome consisting of headache, seizures, visual changes, and other neurologic disturbances in patients with elevated systemic blood pressure. The purpose of this study was to analyze the imaging findings in 14 patients with hypertensive encephalopathy. CT (n = 13), MR (n = 12), and single-photon emission computed tomography (n = 2) examinations performed in these patients before and after resolution of symptoms were reviewed. Eight had the preeclampsia-eclampsia syndrome, and six had hypertensive encephalopathy due to other causes. CT and MR findings in all patients having these examinations were indicative of edema in the cortex and subcortical white matter in the occipital lobes. Two of the 14 patients also had similar findings in the cerebellum and frontal lobes. Single-photon emission computed tomography showed increased vascular perfusion adjacent to areas that appeared abnormal on CT and MR. The findings on the imaging studies resolved on follow-up examinations performed after the hypertension was corrected. Our results suggest that the radiologic findings associated with hypertensive encephalopathy may be useful in establishing the diagnosis in the appropriate clinical setting. PMID- 1632362 TI - Gadopentetate dimeglumine-enhanced MR imaging of the postoperative lumbar spine: comparison of fat-suppressed and conventional T1-weighted images. AB - OBJECTIVE: Gadopentetate dimeglumine-enhanced T1-weighted MR imaging has been used to distinguish epidural fibrosis from recurrent disk herniation in the postoperative lumbar spine. Potential interpretative difficulties relate to detection of subtle contrast enhancement and distinction of enhanced tissue from surrounding epidural fat. The objective of this study was to evaluate the utility of fat-suppressed T1-weighted imaging in improving the depiction of postoperative abnormalities. SUBJECTS AND METHODS: Forty-one patients with recurrent signs and symptoms after previous laminectomy and diskectomy were examined with conventional and fat-suppressed T1-weighted imaging before and after IV administration of gadopentetate dimeglumine. MR images were analyzed for the presence or absence of an epidural soft-tissue mass located anterior and/or lateral to the thecal sac. When such masses were identified, their contrast enhancement behavior was characterized according to the volume, intensity, and pattern of enhancement. Epidural fibrosis was diagnosed by using established MR imaging criteria. In patients with evidence of recurrent disk herniation, diagnosis was based on surgery in six patients and on MR imaging findings in the remainder. RESULTS: Soft-tissue masses were present at 32 of the 43 levels operated on, representing epidural fibrosis (n = 21) or disk herniation (n = 11). Fat suppression improved depiction of contrast enhancement associated with sites of epidural fibrosis. The extent, intensity, and homogeneity of enhancement was greater with fat suppression than with conventional imaging, although the ability to distinguish epidural fibrosis from recurrent disk herniation was not improved. CONCLUSION: Use of the fat-suppression technique results in increased relative intensity and homogeneity of contrast enhancement associated with sites of epidural fibrosis. However, it does not result in significant improvement in the ability to differentiate fibrotic tissue from recurrent disk herniation. Fat suppression does not appear to be indicated for routine use in imaging of the postoperative lumbar spine, but may be useful as a problem-solving tool in selected patients. PMID- 1632364 TI - Fast spin-echo high-resolution MR imaging of the inner ear. AB - Advances in MR imaging continue to improve our ability to evaluate temporal bone anatomy and disease. CT remains the procedure of choice for fine-detail imaging of bone structures such as ossicular anatomy, but it is not the ideal imaging technique for soft-tissue structures (e.g., the membranous labyrinth and neural structures). Conventional spin-echo MR techniques used to image these structures cannot yield excellent contrast and spatial resolution in clinically acceptable time frames. Conventional spin-echo T1-weighted images lack tissue contrast between fluid (e.g., CSF, endolymph, perilymph), neural tissue, otic capsule septa, and surrounding temporal bone. Conventional T2-weighted imaging of the inner ear is needed to reveal the natural contrast between fluid, neural structures, and bone; unfortunately, the use of conventional T2-weighted images is limited by time constraints when large-matrix, thin-section techniques with more than one excitation are used. Fast spin-echo imaging is a recently developed technique that can provide T2-weighted, thin-section (2-mm) high-resolution images with excellent contrast in a fraction of the time needed for conventional spin-echo techniques. This speed advantage allows us to obtain high-resolution images in clinically acceptable time frames. Images produced by this technique are a useful addition, in conjunction with routine T1- and T2-weighted spin-echo images, in the diagnosis of disorders of the inner ear. PMID- 1632363 TI - Ganglioglioma with leptomeningeal and subarachnoid spread: results of CT, MR, and PET imaging. PMID- 1632365 TI - Primary endodermal sinus tumor of the orbit: MR findings. PMID- 1632366 TI - Diagnosis of von Hippel-Lindau disease in a patient with blindness resulting from bilateral optic nerve hemangioblastomas. PMID- 1632367 TI - Influence of the stopcock on the efficiency of percutaneous drainage catheters: laboratory evaluation. AB - The effects of stopcocks on percutaneous fluid drainage were tested in a laboratory model by using a standard stopcock (6-French inner diameter) and a prototype stopcock (9-French inner diameter) connected to 8-, 10-, 12-, 14-, and 16-French catheters. Catheters were immersed in water alone or in viscous fluid with particulate matter, and the system was connected to low wall suction or gravity drainage. The average volume of fluid aspirated in a given period with and without a stopcock was compared for each catheter. The standard stopcock decreased drainage efficiency for these catheters by 13-42%. This decreased drainage efficiency was worse with the larger catheters. Particulate fluid blocked the stopcock connection for all catheters. With the prototype stopcock, drainage of water alone was reduced by 0-9% for the catheters of different sizes. Particulate fluid did not obstruct the prototype stopcock with any size catheter. With gravity drainage, the volume of water aspirated was reduced by 12-42% with the standard stopcock and by 3-6% with the prototype stopcock. These data suggest that stopcock connections greatly influence the efficiency of the percutaneous drainage systems. Stopcocks with larger inner diameters may improve drainage over that achievable with the stopcocks that are currently available. PMID- 1632368 TI - Percutaneous extraction of biliary stones: value of endoluminal sonography. PMID- 1632369 TI - Desperately seeking reimbursement. PMID- 1632370 TI - The selling of a profession. PMID- 1632371 TI - Mycotic aneurysm of the bronchial artery: a rare cause of hemoptysis. PMID- 1632372 TI - Localized large benign fibroma of the pleura in Poland's syndrome. PMID- 1632373 TI - Pulmonary sequestration: diagnosis based on MR angiographic findings. PMID- 1632374 TI - Hair as a mammographic artifact. PMID- 1632375 TI - Low-cost screening mammography. PMID- 1632376 TI - Gastroduodenal intussusception due to a prolapsed gastric adenoma. PMID- 1632377 TI - Ligamentous compression of the celiac axis. PMID- 1632378 TI - Bilateral posttraumatic adrenal hemorrhage detected with CT. PMID- 1632379 TI - Meniscal tears in marathon runners. PMID- 1632380 TI - Transfemoral venous catheterization through inferior vena caval filters. PMID- 1632381 TI - Periocular pseudocyst caused by a displaced contact lens: CT appearance. PMID- 1632382 TI - CT of schizencephaly. PMID- 1632383 TI - Highlights of the ninth annual Rheumatology on the Beach. PMID- 1632384 TI - Panic disorder and pregnancy. PMID- 1632385 TI - Evaluating pain treatment programs: a literature review. AB - The impetus for this project is an attempt to describe by comparison and literature review a pain control program that would provide active patient participation in a highly structured, intense, objectively graded program of comprehensive functional restoration that meets governmental, medical, moral, and ethical standards. Brena indicates that "...there are too many facilities which claim to be pain clinics ... bewildering physicians about their choice for referring their patients." PMID- 1632386 TI - How do you know when someone is in good recovery? PMID- 1632387 TI - Association of patency of the infarct-related coronary artery with plasma levels of plasminogen activator inhibitor activity in acute myocardial infarction. AB - To examine the fibrinolytic capacity in patients with acute myocardial infarction (AMI), baseline levels of plasma plasminogen activator inhibitor (PAI) activity and tissue-type plasminogen activator (t-PA) antigen were measured in 47 patients with Q-wave AMI who underwent emergent coronary angiography 3.0 +/- 0.2 hours after the symptom onset. They received intracoronary injection of urokinase if their infarct-related arteries were occluded. They were classified into 3 groups according to the patency of the infarct-related artery before and after thrombolytic therapy: the patent group (13 patients), the recanalized group (23 patients) and the occluded group (11 patients). The mean level of plasma PAI activity (IU/ml) was higher in patients with AMI as a whole than in the control group (12.8 +/- 1.6 vs 5.4 +/- 0.5, p less than 0.01). The level was lower in the patent group (3.0 +/- 1.1) and higher in the recanalized (18.6 +/- 2.2) and occluded (10.8 +/- 2.5) groups than in the control group (each p less than 0.01). The level was lower in the occluded than in the recanalized group (p less than 0.01) and 62% of the patients in the occluded group had levels within range of the control group. The mean level of plasma t-PA antigen (ng/ml) was higher in patients with AMI as a whole than in the control group (10.3 +/- 0.8 vs 5.8 +/- 0.3, p less than 0.01). There was no difference in the level among the 3 groups with AMI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632388 TI - Clinical, angiographic and anatomic findings in acute severe ischemic mitral regurgitation. AB - Severe mitral regurgitation (MR) due to coronary artery disease unfavorably alters prognosis for medical therapy and is also associated with increased surgical mortality. In this report, the clinical, angiographic and pathoanatomic findings in 50 consecutive patients with severe ischemic MR were characterized. Forty-two patients (84%) either presented with acute myocardial infarction or a well-documented prior infarction. Eleven patients (22%) were in cardiogenic shock at the time of catheterization. Forty patients (80%) had greater than 70% stenosis of the right and left circumflex coronary arteries with or without left anterior descending coronary artery stenosis. Segmental asynergy of the left ventricular wall was present in 48 patients (96%) and involved the inferior wall in 43 (86%). Mean ejection fraction for the group was 51 +/- 7%. A total of 15 patients had direct inspection of the mitral valve apparatus at surgery or autopsy. Posteromedial papillary muscle involvement was found in 14 patients, fibrosis or necrosis in 10 and rupture in 4, with anterolateral papillary muscle rupture in 1 patient. Thus, acute severe ischemic MR is usually associated with significant narrowing of both right and left circumflex coronary arteries, and posteromedial papillary muscle involvement. PMID- 1632389 TI - Effects of anger on left ventricular ejection fraction in coronary artery disease. AB - This study examined the comparative potency of several psychological stressors and exercise in eliciting myocardial ischemia as measured by left ventricular (LV) ejection fraction (EF) changes using radionuclide ventriculography. Twenty seven subjects underwent both exercise (bicycle) and psychological stressors (mental arithmetic, recall of an incident that elicited anger, giving a short speech defending oneself against a charge of shoplifting) during which EF, blood pressure, heart rate and ST segment were measured. Eighteen subjects had 1-vessel coronary artery disease (CAD), defined by greater than 50% diameter stenosis in 1 artery as assessed by arteriography. Nine subjects served as healthy control subjects. Anger recall reduced EF more than exercise and the other psychological stressors (overall F [3.51] = 2.87, p = .05). Respective changes in EF for the CAD patients were -5% during anger recall, +2% during exercise, 0% during mental arithmetic and 0% during the speech stressor. More patients with CAD had significant reduction in EF (greater than or equal to 7%) during anger (7 of 18) than during exercise (4 of 18). The difference in EF change between patients with CAD and healthy control subjects was significant for both anger (t25 = 2.23, p = 0.04) and exercise (t25 = 2.63, p = 0.01) stressors. In this group of patients with CAD, anger appeared to be a particularly potent psychological stressor. PMID- 1632390 TI - Effects of 8:00 a.m. and 2:00 p.m. doses of isosorbide-5-mononitrate during twice daily therapy in stable angina pectoris. AB - "Trough" plasma concentrations of isosorbide-5-mononitrate (IS-5-MN), an active metabolite of isosorbide dinitrate, of less than 95 ng/ml are considered necessary to prevent development of tolerance to isosorbide dinitrate and IS-5 MN. In a double-blind, crossover, placebo-controlled study, the effects of IS-5 MN during twice daily eccentric therapy were evaluated in 18 patients with reproducible exercise-induced angina who were nitrate responders. In a random order, patients received either placebo or IS-5-MN (20 mg) at 8 a.m. and 2 p.m. for 1 week each. Average trough plasma IS-5-MN concentrations before the 8 a.m. and 2 p.m. doses were 67 and 226 ng/ml, respectively, and increased to 382 and 488 ng/ml 2 hours after the 8 a.m. and 2 p.m. doses, respectively. Despite a more than threefold higher trough plasma IS-5-MN concentration before the 2 p.m. dose than before the 8 a.m. dose, the increase in exercise duration 2 hours after the doses was similar (1.21 minutes [21%] after 8 a.m. dose, and 1.08 minutes [19%] after 2 p.m. dose). These increases in exercise duration after IS-5-MN were significantly (p less than 0.01) greater than those observed after placebo (0.17 minutes [3%] after 8 a.m. dose, and -0.05 minute [-0.5%] after 2 p.m. dose). Reduction in standing systolic blood pressure at 2 hours after the doses was also nearly identical after the 8 a.m. and 2 p.m. doses of IS-5-MN (21 [15%] and 19 [14%] mm Hg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632391 TI - Background and methods for the lovastatin restenosis trial after percutaneous transluminal coronary angioplasty. The Lovastatin Restenosis Trial Study Group. AB - Restenosis remains a critical limitation of percutaneous transluminal coronary angioplasty (PTCA). Recent experimental and clinical data have suggested that lovastatin, an hydroxymethylglutaryl coenzyme A reductase inhibitor, may reduce the rate of restenosis through reduction of low density-lipoprotein (LDL) cholesterol or possibly by direct effects. Lovastatin may therefore produce favorable alterations in endothelial healing, resulting in a decreased smooth muscle cell proliferative response to injury after angioplasty. Emory University, in conjunction with Merck Research Laboratories, has initiated a 10-center double blinded, placebo-controlled, randomized trial to assess the effect of both pretreatment and aggressive lipid lowering with lovastatin in reducing the rate of restenosis. Lovastatin achieves approximately 75% of its effect on LDL cholesterol by 1 week. Thus, patients scheduled for PTCA are randomly assigned pretreatment with lovastatin, 40 mg twice daily, or placebo 7 to 10 days before PTCA. Therapy is continued for 6 months, at which time repeat coronary arteriography is performed. A detailed safety algorithm was designed, with patients receiving lovastatin and matching placebo back-titrated on a 1:1 basis for LDL cholesterol less than 50 mg/dl. The power is a 90%, alpha = 0.05, 2 tailed test to reduce restenosis from 30 to 15%. The sample size is 360 patients in the 2 arms; allowing for a 10% dropout rate, approximately 400 patients will be randomized. Patients with successful PTCA, less than 50% residual diameter stenosis and greater than or equal to 20% diameter stenosis reduction are analyzed for restenosis at 4 to 6 months by quantitative coronary arteriography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632392 TI - Usefulness of left ventricular size and function in predicting survival in chronic dialysis patients with diabetes mellitus. AB - To identify patients at high risk for sudden death, a group of stable patients on maintenance dialysis with diabetes mellitus were studied for up to 135 months to determine if there were clinical, laboratory or echocardiographic predictors of high risk. Eighty-two patients on maintenance dialysis who underwent clinical, laboratory evaluation and echocardiography were enrolled and followed for a mean of 25 months for cardiac and noncardiac complications. Thirty-seven patients with normal wall motion and left ventricular (LV) internal diameter had a mean survival of 35.8 months; 28 patients survived greater than 12 months. Seven patients with normal LV wall motion and dilated LV cavities had a mean survival of 45.7 months; 7 patients survived greater than 12 months. Fifteen patients with abnormal LV wall motion and normal internal LV dimensions had a mean survival of 17 months; 7 patients survived greater than 12 months. Twenty-three patients with both abnormal LV wall motion and dilated LV cavities had a mean survival of 7.8 months; 5 patients survived greater than 12 months. Although echocardiographic abnormalities predicted cardiac mortality at 6 and 12 months, the combination of an abnormal standard electrocardiogram at baseline, clinical history of angina pectoris, and prior documented myocardial infarction or congestive heart failure did not. When the study group was divided by mode or duration of dialysis, presence or absence of diabetes, or use of cardioactive drugs, echocardiographic LV wall motion abnormalities remained the most important determinant of survival. PMID- 1632393 TI - Prospective comparison of biphasic and monophasic shocks for implantable cardioverter-defibrillators using endocardial leads. AB - Bidirectional shocks using 2 current pathways have been used in endocardial lead systems for implantable cardioverter-defibrillators, but the optimal shock waveform for endocardial defibrillation is unknown. The clinical efficacy and electrical characteristics of bidirectional monophasic and biphasic shocks for endocardial cardioversion-defibrillation of fast monomorphic or polymorphic ventricular tachycardia (VT), or ventricular fibrillation (VF) were evaluated. Thirty-three patients (mean age 60 +/- 12 years, and mean left ventricular ejection fraction 34 +/- 13%) were studied. Defibrillation catheter electrodes were located in the right ventricular apex and superior vena cava/right atrial junction. A triple-electrode configuration including the 2 catheter electrodes and a left thoracic patch was used to deliver bidirectional shocks from the right ventricular cathode to an atrial anode (pathway 1) and the thoracic patch (pathway 2). The shock waveforms examined were sequential and simultaneous monophasic, and simultaneous biphasic. The efficacy of 580 V (20 J) shocks for fast monomorphic VT were comparable for the 3 waveforms (73% for sequential monophasic, 73% for simultaneous monophasic, and 100% for simultaneous biphasic). However, for polymorphic VT and VF, 580 V sequential monophasic shocks had a significantly lower efficacy (25%) than did simultaneous monophasic (75%; p = 0.01) or biphasic (89%; p less than 0.001) shocks. Single-shock defibrillation thresholds with simultaneous biphasic shocks were significantly lower (9 +/- 5 J) than were those with simultaneous monophasic shocks (15 +/- 4 J; p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632394 TI - Comparison of decremental and burst overdrive pacing as treatment for ventricular tachycardia associated with coronary artery disease. AB - Several forms of antitachycardia pacing have been used successfully for terminating cardiac arrhythmias, and implantable devices now incorporate a tier of overdrive pacing for treating of ventricular tachycardia (VT). No consensus exists regarding the optimal mode of pacing therapy. Accordingly, a prospective, randomized, crossover study of antitachycardia pacing was performed to analyze the effects of 2 decremental forms (10 and 5 ms) and a synchronized burst overdrive pacing mode on episodes of VT. Overdrive antitachycardia pacing was an effective therapy (78%) for terminating VT. Burst overdrive pacing and an autodecremental pacing protocol, incorporating a 10 ms decrement, were found to be effective and comparable forms of therapy. Both of these pacing methods were superior in terminating VT when compared with a pacing scheme using a 5 ms coupling decrement (p less than 0.01). Tachycardia acceleration occurred in 6.4% of the episodes of VT. None of the pacing methods displayed a specific propensity for tachycardia acceleration, and no measure of tachycardia segments identified a predilection for pace terminability. Antitachycardia pacing is an effective therapy for VT and different pacing formulas have variable effects. Further, these effects appear to be independent of tachycardia cycle length and variability. PMID- 1632395 TI - Establishment of signal-averaged electrocardiographic criteria with Frank XYZ leads and spectral filter used alone and in combination with ejection fraction to predict inducible ventricular tachycardia in coronary artery disease. AB - Signal-averaged electrocardiographic criteria are reported for corrected Frank XYZ leads and a spectral filter. The new criteria were used alone and in combination with ejection fraction to predict inducibility of ventricular tachycardia (VT) at electrophysiologic testing. Signal-averaged electrocardiographic criteria were developed in 87 control subjects and validated in 182 patients (aged 63 +/- 10 years) with coronary artery disease and QRS duration less than 118 ms. Patients underwent electrophysiologic testing in which up to 3 extra-stimuli were used during 2 paced drives from 2 right ventricular sites. A positive finding was monomorphic VT lasting 30 seconds or needing intervention. An ejection fraction less than 40% was considered abnormal. Signal averaged electrocardiographic variables that best characterized control subjects and separated patients with and without inducible VT were filtered QRS duration less than 120 ms, low-amplitude signal duration less than 38 ms and root-mean square voltage greater than 20 muv. With these criteria, signal-averaged electrocardiographic and ejection fraction sensitivities were 87 and 45%, respectively, and specificities were 65 and 77%, respectively. Combining signal averaged electrocardiography with ejection fraction improved the predictive accuracy. In conclusion, diagnostic criteria for signal-averaged electrocardiography with use of Frank XYZ leads and a spectral filter produced results similar to those reported for use of bipolar XYZ leads and a Butterworth filter. Signal-averaged electrocardiography was a better predictor of VT than was ejection fraction. PMID- 1632396 TI - Comparison of direct-current and radiofrequency ablation of free wall accessory atrioventricular pathways in the Wolff-Parkinson-White syndrome. AB - To evaluate and compare the safety and efficacy of catheter-mediated direct current (DC) or radiofrequency (RF) ablation in patients with free wall accessory atrioventricular pathways, 95 patients with free wall accessory atrioventricular pathway-mediated tachyarrhythmias underwent catheter ablation. Immediately after ablation, 27 of 30 accessory pathways (90%) were ablated successfully with DC, but 2 of the 27 had early return of conduction and received a second ablation session; 3 of 8 (38%) and 57 of 62 (92%) accessory pathways were ablated successfully with RF through a small-tip (2 mm) and a large-tip (4 mm) electrode catheter, respectively. Complications in DC ablation included transient hypotension (2 patients) and pulmonary air-trapping (2 patients) and in RF ablation, cardiac tamponade (1 patient) and suspicious aortic dissection (1 patient); myocardial injury and proarrhythmic effects were more severe in DC ablation. Procedure and radiation exposure time were significantly longer in RF ablation (DC, 3.6 +/- 0.2 hours, 34 +/- 4 minutes; RF 4.2 +/- 0.5 hours, 50 +/- 10 minutes). This study confirms that RF ablation is associated with little morbidity and few complications, and RF ablation with a large-tip electrode catheter is an effective and relatively safe nonsurgical method for treatment of free wall accessory atrioventricular pathway-mediated tachyarrhythmias. PMID- 1632397 TI - Clinical implications of left atrial spontaneous echo contrast in nonrheumatic atrial fibrillation. AB - The prevalence and clinical significance of left atrial (LA) spontaneous echo contrast were investigated in 103 consecutive patients with chronic nonrheumatic atrial fibrillation (AF) using transesophageal echocardiography. LA spontaneous echo contrast was visualized in 25 of 103 patients (24.3%). Age, sex, LA diameter, left ventricular diastolic and systolic dimensions, left ventricular ejection fraction, and the percentage of lone AF were not significantly different between patients with and without LA spontaneous echo contrast; however, those with LA spontaneous echo contrast were less likely to have moderate or severe mitral regurgitation. LA thrombi were observed in 7 patients (6.8%), and all 7 thrombi were found in the atria with spontaneous echo contrast. History of cerebral ischemia or peripheral embolism, or both, was significantly more frequent in patients with than without LA spontaneous echo contrast (84 vs 18%; p less than 0.001). The presence of LA spontaneous echo contrast was highly specific (94%) and predictive for thromboembolic events (positive and negative predictive values of 84 and 82%, respectively). Thus, transesophageal echo detected LA spontaneous echo contrast is frequently found in patients with chronic nonrheumatic AF. This phenomenon may represent a precursor of thrombus formation, and its presence is associated with an increased thromboembolic risk. PMID- 1632398 TI - Relation between QT and RR intervals during exercise testing in atrial fibrillation. AB - The ability to predict the RR-QT relation over a range of heart rates was evaluated in 10 patients with atrial fibrillation (AF) and in 10 control subjects in sinus rhythm. The data from each subject were fitted by regression into 3 QT prediction formulas (the square root formula of Bazett, the cube root formula of Fridericia and the exponential formula of Sarma) applied in standard form and modified with a weighted average of the preceding 5 RR intervals. The goodness-of fit of each formula was evaluated using mean square residual and Akaike information criterion. For AF, the mean square residuals did not differ among the 3 standard QT prediction formulas (Bazett 624 +/- 274, Fridericia 625 +/- 274 and Sarma 611 +/- 267) and among the 3 modified QT prediction formulas (Bazett 507 +/ 325, Fridericia 496 +/- 255 and Sarma 495 +/- 328). The weighted average modification produced a significant decrease in mean square residuals for all 3 equations (p less than 0.05) in all patients. These findings were confirmed by Akaike information criterion. Goodness-of-fit in sinus rhythm was similar to previously published reports, and significantly better than the fit for AF (p less than 0.0001). For 9 of the 10 patients with AF, sinus rhythm electrocardiograms were obtained and the above regression equations were used to predict QT intervals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632399 TI - A controlled trial of acute and long-term medical therapy in tilt-induced neurally mediated syncope. AB - To study the efficacy of medical treatment for preventing syncopal recurrences in patients affected by tilt-induced neurally mediated syncope, a randomized placebo treatment prospective study was performed in 30 patients (10 men and 20 women, mean age 42 +/- 21 years) who had syncope reproduced in 2 consecutive head-up tilt-table tests without pharmacologic intervention (n = 20) or during isoproterenol infusion (n = 10). Patients were randomly assigned to 2 groups: 15 to placebo, and 15 to drug therapy (determined on the basis of serial pharmacologic tilting tests). Therapy was either atenolol (n = 7), dihydroergotamine (n = 2), domperidone (n = 2), cafedrine (n = 1), or elastic compression stockings, alone or in association with drugs (n = 3). During a mean of 10 +/- 7 months of follow-up, syncope recurred in 3 patients (20%) in the treatment group and in 4 (27%) in the placebo group; actuarial rates of absence of syncopal recurrences after 20 months were 70 and 67%, respectively. Thus, the outcome of either treated or untreated patients was favorable (with a low recurrence rate of syncope), and the usefulness of tilting-guided medical therapy remains uncertain. PMID- 1632400 TI - Accuracy of various methods of localization of the orifice of the coronary sinus at electrophysiologic study. AB - The coronary sinus (CS) orifice is an important reference point for determining electrode and, thereby, accessory pathway location at electrophysiologic study. The reliability of fluoroscopic landmarks used to identify the CS orifice is not known. This study compared the accuracy of several fluoroscopic landmarks for identifying the CS orifice with the location defined by radiopaque contrast injection of the CS. Forty patients were studied. Radiographic markers of the CS orifice that were examined included: (1) the point at which the CS catheter prolapsed during advancement, (2) the point of maximum convexity of the CS catheter when a superior vena caval approach was used, (3) the right side of the ventricular septum, and (4) the relation to the underlying vertebrae. The least significant difference method of multiple comparisons was used for statistical analysis. The point at which the CS catheter prolapsed was the most accurate noncontrast method for determining the location of the CS orifice (p less than 0.05), but was possible without the use of excessive force in only 48% of patients. The point of catheter prolapse was a median of 1 mm (range 0 to 11) from the true location of the os. Errors with other examined landmarks ranged up to 3 cm. Identification of the CS orifice is best performed by radiopaque contrast injection. The point of prolapse during catheter advancement in the CS is an accurate alternative when contrast injection is not feasible. Other noncontrast fluoroscopic landmarks are less reliable and are best avoided.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632401 TI - Studies of Left Ventricular Dysfunction (SOLVD) Registry: rationale, design, methods and description of baseline characteristics. AB - The Studies of Left Ventricular Dysfunction (SOLVD) comprises 2 double-blind, randomized clinical trials to test improved survival by angiotensin-converting enzyme inhibitor in patients with left ventricular dysfunction, with or without congestive heart failure. Patients entering the trials may be a highly selected subset of the population of such patients; those with the worst and best prognosis are likely to be excluded. To obtain the clinical history of a broader group, a registry of 6,273 patients included a relatively unselected cohort of patients with heart failure or left ventricular dysfunction, or both, from SOLVD hospitals. Registry data were obtained from hospital records. Because data collection from medical records may lead to incomplete data and more investigations in "sicker" patients, 898 randomly chosen subjects from different disease strata were seen in clinic where neurohumoral measures, echocardiograms, x-rays and electrocardiograms were obtained, and a 6-minute walking test was performed. The design and methodologic features, and the baseline characteristics of the participants in this 2-tiered registry are described, and its use in complementing the results and interpretation of the SOLVD trials is discussed. PMID- 1632402 TI - Effects of once-daily benazepril therapy on exercise tolerance and manifestations of chronic congestive heart failure. The Benazepril Heart Failure Study Group. AB - The effects of the long-acting angiotensin-converting enzyme inhibitor benazepril hydrochloride on exercise tolerance and signs and symptoms of congestive heart failure (CHF) were evaluated in a double-blind, multicenter, placebo-controlled clinical trial. Patients with chronic New York Heart Association class II to IV symptoms of CHF and an ejection fraction by radionuclide scanning of less than or equal to 35% were randomized in a 2:1 ratio to treatment with ascending doses of oral benazepril (n = 114) or placebo (n = 58) once daily, while continuing to receive background therapy with digoxin and diuretics. After randomization, patients were evaluated clinically every 2 weeks during a 12-week, double-blind treatment period. Maximal exercise tolerance was measured before and at specified time points after randomization by graded treadmill exercise testing. At week 12, mean exercise time increased 95 +/- 12 (SEM) seconds in the group receiving benazepril, whereas the increase was 37 +/- 18 seconds in the group receiving placebo (p less than 0.01 for the difference between the groups). There was also greater improvement in overall clinical status and in the signs and symptoms of CHF in benazepril-treated patients than in control subjects. There were 3 deaths in placebo-treated patients and none in benazepril-treated patients (p less than 0.05); the overall incidence of adverse effects was identical in the 2 groups. Benazepril is a well-tolerated angiotensin-converting enzyme inhibitor that provides clinically important improvement in exercise tolerance and in signs and symptoms when given once daily to patients with CHF receiving background therapy with digoxin and a diuretic. PMID- 1632403 TI - Comparison between New York Heart Association classification and peak oxygen consumption in the assessment of functional status and prognosis in patients with mild to moderate chronic congestive heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy. AB - To compare the value of the New York Heart Association (NYHA) classification and measurement of peak oxygen consumption (VO2) in the assessment of functional status and prognosis in patients with mild to moderate chronic congestive heart failure (CHF), 94 patients with clinically stable NYHA class II and III CHF were prospectively studied. In all patients, left ventricular ejection fraction was less than or equal to 40% (mean 22 +/- 9); 49 patients were in NYHA class II, and 45 were in NYHA class III. Mean peak VO2 was 17 +/- 5 ml/min/kg. During a follow up period of 23 +/- 11 months, 21 patients died. The 1-, 2- and 3-year cumulative survival rates for the 94 patients were 88, 79 and 69%, respectively. Functional status, as assessed both by peak VO2 and NYHA classification, and left ventricular ejection fraction were significantly worse in the group of nonsurvivors. The most powerful independent predictor of mortality was peak VO2. Although mean peak VO2 was significantly higher in NYHA class II than in NYHA class III (20 +/- 4 vs 13 +/- 3 ml/min/kg, p less than 0.0001), categorization into subgroups on the basis of the attained peak VO2 revealed a marked discrepancy with the NYHA classification. Nevertheless, the survival curves of patients subdivided at a peak VO2 of 16 ml/min/kg showed a strong resemblance with survival curves of both NYHA classes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632404 TI - Ventricular septal defect in the first year of life. AB - Of approximately 22,000 live births in the region under study during the last 4 years, ventricular septal defect (VSD) was identified as the primary or isolated congenital heart lesion in 124 infants who were followed up from birth for a minimum of 1 year (incidence, 5.7 per 1,000 live births). Doppler color flow mapping was performed in 93 of 124 patients; 47 had a muscular VSD and 46 had a perimembranous VSD. Only 1 patient had 2 muscular VSDs. None had a subpulmonic type of defect. Of 124 patients, 14 were lost to follow-up. Spontaneous closure was seen in 18 patients (42%) in the muscular group, in 9 (23%) in the perimembranous group and in 10 patients (37%) in the unclassified group by the end of the first year. The overall rate of spontaneous closure was 34% by the end of the first year. Congestive heart failure developed in 2 of 46 patients with muscular VSD and in 12 of 47 patients with perimembranous VSD. In the first year, 2 patients with muscular VSD as opposed to 5 with perimembranous VSD required surgery. Doppler color flow mapping is a valuable aid in the diagnosis of VSD and may be one reason for the observed increase in the incidence of VSD. The overall prognosis appeared much better in the muscular than the perimembranous type of VSD. PMID- 1632405 TI - Changes in pulmonary hemodynamics with aging in a predominantly hypertensive population. AB - The impact of aging on pulmonary hemodynamics was investigated in 322 patients who underwent right- and left-sided cardiac catheterization and echocardiographic examination, and were free of coronary disease, impaired left ventricular systolic function and left ventricular dilatation. Most of the patients were black (83%) and hypertensive (78%). Mean pulmonary artery pressures increased progressively with age: 16.7 +/- 4.6, 17.9 +/- 6.4 and 20.6 +/- 8.0 mm Hg for those aged less than 45 (n = 50), 45 to 64 (n = 238) and greater than or equal to 65 years (n = 34), respectively (p = 0.020). Pulmonary vascular resistance was 99 +/- 42, 116 +/- 62 and 160 +/- 68 dynes s cm-5, and the ratio of pulmonary to systemic vascular resistance was 78, 80 and 105%, respectively, for the 3 age groups (p less than 0.001). Along with these changes, a decrease in cardiac output and an increase in systolic blood pressure and systemic vascular resistance with age were noted. The effect of age on mean pulmonary artery pressure and pulmonary vascular resistance was statistically significant after adjustment for gender, smoking status, body weight, left ventricular hypertrophy, systolic blood pressure and systemic vascular resistance. Consideration should be given to age-related changes in the pulmonary circulation when defining physiologically normal values. PMID- 1632406 TI - Left ventricular function and dimensions in newly diagnosed non-insulin-dependent diabetes mellitus. AB - Left ventricular (LV) function and dimensions were assessed with Doppler and M mode echocardiography in 26 men and 17 women with newly diagnosed non-insulin dependent diabetes mellitus, and in 13 healthy control men and 13 women. The diabetic men had lower peak filling rate normalized to mitral stroke volume than the control men (mean +/- standard error of the mean, 4.2 +/- 0.1 vs 4.9 +/- 0.3 stroke volume/s, p less than 0.01). The diabetic women had increased LV mass (102 +/- 12 vs 86 +/- 8 g/m2, p less than 0.01) and decreased fractional shortening (34 +/- 1 vs 38 +/- 1%, p less than 0.05) when compared with control women. At 3 and 15 months, 23 diabetic men and 15 women were reexamined. Concomitantly with decreasing blood glucose levels, fractional shortening improved mainly during the first 3 months and was significantly higher in both diabetic men (36 +/- 2 vs 30 +/- 2%, p less than 0.05) and women (38 +/- 1 vs 34 +/- 1%, p less than 0.05) at 15 months than at baseline. In the diabetic men, peak filling rate increased from 4.3 +/- 0.1 stroke volume/s at baseline to 4.8 +/- 0.2 stroke volume/s at 15 months (p less than 0.05). At 15 months, peak filling rate was correlated (r = 0.61, p less than or equal to 0.001) with autonomic nervous function assessed as heart rate variability during deep breathing test in diabetic men who also showed an inverse correlation between LV hypertrophy and heart rate variability throughout the follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632408 TI - Questions unresolved by the Third International Study of Infarct Survival. PMID- 1632407 TI - Three-dimensional reconstruction of human carotid arteries from images obtained during noninvasive B-mode ultrasound examination. AB - Previous investigators have demonstrated that B-mode ultrasonography can provide high resolution images of the carotid arteries. When combined with Doppler flow measurements, quantitative estimates of luminal narrowing may also be obtained. B mode imaging is limited, however, in its ability to provide a composite view of the vessel wall, lumen and plaque. Spatial relations between structures visualized in individual frames must be inferred from repeated transducer passes over the designated site, or repeated review of recorded images, followed by a "mind's eye" reconstruction. Three-dimensional (3-D) reconstruction of serially recorded cross-sectional images from current B-mode systems represents a possible solution to this limited spatial display that preserves detail regarding vessel wall pathology. Accordingly, computer-based automated 3-D reconstruction was used to generate a tangible format with which to assess and compare serially and transcutaneously recorded 2-dimensional (2-D) B-mode images of the carotid arteries. One or more timed sweep recordings of the 2-D B-mode examination were obtained from 5 patients for 3-D reconstruction. In all cases, satisfactory 3-D reconstruction was accomplished in three 3-D formats: cylindrical, sagittal and lumen cast. Sagittal 3-D reconstruction provided information regarding pathologic alterations within the arterial wall. Experience with the cylindrical mode suggests that this 3-D format, particularly when the reconstructed vascular segment is hemisected, is optimally suited for those cases in which direct inspection of luminal topography is of special interest. The lumen cast display, used with a recently validated edge-detection algorithm, may enhance the use of B mode ultrasound for assessment of luminal cross-sectional area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632409 TI - Good old boys, Texas, big numbers and coronary artery bypass grafting. PMID- 1632410 TI - Pulse oximetry in cyanotic congenital heart disease. PMID- 1632411 TI - Effects of homograft blood type and anatomic type on stenosis, regurgitation and calcium in homografts in the pulmonary position. PMID- 1632412 TI - Electrocardiographic features of restrictive pulmonary disease, and comparison with those of obstructive pulmonary disease. PMID- 1632413 TI - Usefulness of transesophageal echocardiography in diagnosing lipomatous hypertrophy of the atrial septum with comparison to transthoracic echocardiography. PMID- 1632414 TI - Spontaneous disappearance of cough induced by angiotensin-converting enzyme inhibitors (captopril or enalapril). PMID- 1632415 TI - Frequency of stress-induced thallium-201 defects in patients with patent internal mammary artery to the left anterior descending coronary artery graft. PMID- 1632416 TI - Angiographic follow-up after internal mammary artery graft angioplasty. PMID- 1632417 TI - Diagnostic significance of deep T-wave inversion induced by exercise testing in patients with suspected coronary artery disease. PMID- 1632418 TI - Increase in platelet support of thrombin generation after thrombolytic therapy. PMID- 1632419 TI - Prevalence of arrhythmias detected by 24-hour ambulatory electrocardiography and value of antiarrhythmic therapy in elderly patients with unexplained syncope. PMID- 1632420 TI - Multi-level analysis in epidemiologic research on health behaviors and outcomes. AB - Individual-level health behaviors and outcomes have multi-level determinants (individual and environmental). Multi-level analysis seeks to explain individual outcomes in terms of both individual and environmental or aggregate variables. Ecologic fallacy (improper inference about individual-level associations based on associations measured only at the aggregate level) can result from confusion about the level of inference that is of ultimate interest. The perspective of multi-level analysis acknowledges the importance of both individual and environmental variables in determining health behaviors and outcomes at the level of the indivisible unit--the individual. The authors review concepts and methods of multi-level analysis and their application to epidemiologic research on health behavior and health outcomes. PMID- 1632421 TI - Vitamin supplement use and reduced risk of oral and pharyngeal cancer. AB - Use of vitamin and mineral supplements was assessed in a population-based case control study of oral and pharyngeal cancer, conducted during 1984-1985 in four areas of the United States. There was no association with intake of multivitamin products, but users of supplements of individual vitamins, including vitamins A, B, C, and E, were at lower risk after controlling for the effects of tobacco, alcohol, and other risk factors for these cancers. After further adjustment for use of other supplements, vitamin E was the only supplement that remained associated with a significantly reduced cancer risk. The adjusted odds ratio of oral and pharyngeal cancer for "ever regularly used" vitamin E was 0.5 (95% confidence interval 0.4-0.6). To the authors' knowledge, this is the first epidemiologic study to show a reduced oral cancer risk with vitamin E use. Although it is not clear that the lower risk among consumers of vitamin E supplements is due to the vitamin per se, the findings are consistent with experimental evidence and should prompt further research on the role of vitamin E and other micronutrients as inhibitors of oral and pharyngeal cancer. PMID- 1632422 TI - Mortality from melanoma in migrants to Australia: variation by age at arrival and duration of stay. AB - All death records in Australia during the period 1964-1985 were analyzed to compare mortality from melanoma in immigrants and Australian-born individuals, and to investigate changes in risk in the immigrants according to their duration of stay and age at arrival. About 450,000 deaths were from cancer, and risks of melanoma were estimated by logistic regression relative to those of the Australian-born, with deaths from other cancers used as controls. Estimates were adjusted for age at death, time period, birth cohort, and state of registration of death in Australia. Region of birth was defined as New Zealand, other Oceania, England, Ireland/Scotland/Wales (including Northern Ireland and the Republic of Ireland), Central Europe, Eastern Europe, Southern Europe, Western Asia, or Eastern Asia, bearing in mind that many migrants born in Asia were of European descent. Overall, migrants from outside Oceania were at lower risk than the Australian-born, and the lowest risks in males were in Southern Europeans and Eastern Asians, reflecting the protective effect of a darker complexion. Risk of melanoma was related both to duration of stay in Australia and to age at arrival; although their relative importance cannot be measured, the patterns of change suggested that childhood migration may be more important in determining risk than number of years in Australia. The authors believe this study to be based on the largest data set ever used in migrant studies, and note that the previously found differences in melanoma risk between immigrants and Australian-born remained after adjustment for major temporal and geographic confounders. The results confirm the importance of the interaction between environmental and genetic risk factors in the etiology of melanoma. PMID- 1632423 TI - Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals. AB - The authors assessed the reproducibility and validity of an expanded 131-item semiquantitative food frequency questionnaire used in a prospective study among 51,529 men. The form was administered by mail twice to a sample of 127 participants at a one-year interval. During this interval, men completed two one week diet records spaced approximately 6 months apart. Mean values for intake of most nutrients assessed by the two methods were similar. Intraclass correlation coefficients for nutrient intakes assessed by questionnaires one year apart ranged from 0.47 for vitamin E without supplements to 0.80 for vitamin C with supplements. Correlation coefficients between the energy-adjusted nutrient intakes measured by diet records and the second questionnaire (which asked about diet during the year encompassing the diet records) ranged from 0.28 for iron without supplements to 0.86 for vitamin C with supplements (mean r = 0.59). These correlations were higher after adjusting for week-to-week variation in diet record intakes (mean r = 0.65). These data indicate that the expanded semiquantitative food frequency questionnaire is reproducible and provides a useful measure of intake for many nutrients over a one-year period. PMID- 1632424 TI - Body mass index and body girths as predictors of mortality in black and white men. AB - Anthropometric measurements collected from black and white men in the 1960 (n = 946) and 1963 (n = 456) examinations of the Charleston Heart Study cohort (Charleston County, South Carolina) were examined as predictors of all cause and coronary heart disease mortality. Anthropometric measurements included body mass index, chest girth (at the third intercostal space), abdominal girth (at the umbilicus) and midarm circumference. Vital status of 98 percent of the cohort was determined through 1988. Body mass index was not associated with mortality in the white men; however, it was predictive of all cause and coronary heart disease mortality in the black men. Analyses conducted separately in the lower and upper range of body mass index in black men showed the adjusted relative hazard at the 50th versus the 10th percentile of body mass index was 0.54 for all cause mortality, but was not significant for coronary heart disease mortality; whereas the adjusted relative hazard for the 90th relative to the 50th percentile was 1.7 for coronary heart disease deaths, but not significant for deaths from all causes. The circumference measurements were not predictive of all cause or coronary heart disease mortality in the white men. In the black men, the adjusted relative hazard ratios for all cause mortality for the 85th relative to the 15th percentiles were 0.22 for midarm circumference and 2.0 for abdominal circumference. PMID- 1632425 TI - Methods for inference on transmission in seroprevalence data for multiple infections. AB - When risk factors for an infectious disease are unknown, a method commonly employed is to investigate parallels with known infections (covariate infections). Data sets of value here are those for specified populations in which the seroprevalence of antibodies for multiple infections has been ascertained. The use of markers of covariate infections in multivariable analyses is problematic when the covariate infection is not itself an independent risk factor for the outcome of interest. In the performance of these analyses, the authors recommend the following strategy: 1) For estimates of the effects of measured risk factors on the outcome, adjustment for the covariate infection should not be done; this will avoid problems of overadjustment. 2) After control for the measured risk factors, an estimate of the "effect" of the covariate infection may be used as an indicator of the presence of unmeasured shared risk factors. 3) When shared, measured risk factors exist, the authors propose the use of methods developed for analysis of repeated measures of categorical variables to assist in inference about shared mechanisms of action of these risk factors. This analytic strategy takes advantage of the method of analogy for building understanding of transmission of new agents through their parallels with better known ones and is useful in the development of hypotheses. PMID- 1632426 TI - Serial changes in blood pressure from adolescence into adulthood. AB - High blood pressure is an established risk factor for cardiovascular disease outcomes in adulthood. Furthermore, numerous longitudinal studies of blood pressure in childhood with length of follow-up from 1 to 17 years indicate that blood pressure levels track over the short term. This study addresses the question of the predictive value of childhood blood pressure readings for adult levels, using repeated blood pressure determinations from a sample of 501 participants in the Fels Longitudinal Study, an ongoing cohort study in southwestern Ohio that began in 1929. A damped autoregressive model indicated tracking correlations from 0.39 (4-year intervals) to 0.24 (20 years) for systolic pressure and 0.37 (4 years) to 0.20 (20 years) for diastolic pressure. These results indicate that tracking of blood pressure persists from age 13 years to age 40 years, which translates into moderate levels of relative risk for adult hypertension (diastolic pressure above 90 mmHg) for adolescents with high normal blood pressure. The estimated relative risks of hypertension at age 35 for white 15-year-olds with a true mean diastolic pressure of 80 mmHg were 1.9 for males and 2.6 for females, relative to 15-year-olds with a true diastolic pressure of 60 mmHg. PMID- 1632427 TI - Re: "Breast cancer and cigarette smoking: a hypothesis". PMID- 1632428 TI - Re: "Breast cancer and cigarette smoking: a hypothesis". PMID- 1632429 TI - Re: "Statistical reasoning in epidemiology". PMID- 1632430 TI - Preaxial polydactyly of feet in infants of diabetic mothers: epidemiological test of a clinical hypothesis. AB - Using data from the Spanish Collaborative Study of Congenital Malformations (ECEMC), we tested the hypothesis of Carey et al. (Proc Greenwood Genet Cent 9:95, (1990) on maternal diabetes and preaxial polydactyly of feet in infants born to diabetic mothers. Our results seem to confirm their suggestion, although the hallucal type of preaxial polydactyly that they described seems to be much less frequent. Nevertheless, a high risk exists (OR = 24.60, P = 0.0004) for preaxial polydactyly of the feet in relation with other types of birth defects or postaxial polydactyly. This analysis shows the importance of clinical observations for epidemiologists, because such observations constitute hypotheses and provide actual issues for study, and clinicians will get epidemiological confirmation for their individual observations and hypotheses. PMID- 1632431 TI - Phenotypically normal girl with male pseudohermaphroditism, hypoplastic left ventricle, lung aplasia, horseshoe kidney, and diaphragmatic hernia. PMID- 1632432 TI - Psoriasis vulgaris, fetal growth, and genomic imprinting. AB - We report on 2 independent lines of evidence suggesting genomic imprinting of a major gene for psoriasis vulgaris. First, the birth weight of children from psoriatics is influenced by the sex of the psoriatic parent. Children from fathers with psoriasis are considerably (270 g) heavier than children from mothers with psoriasis (P less than 0.004). Second, the disease manifestation (penetrance) depends in part on the sex of the psoriatic parent. Offspring from fathers with psoriasis and male "gene carriers" are significantly (P less than 0.015 and P less than 0.007) more often affected than offspring from mothers with psoriasis and female "gene carriers." Of 91 grandchildren with psoriasis 59 (65%) have an affected grandfather and 32 (35%) a psoriatic grandmother. This deviation from the expected distribution is significant (P less than 0.04). Genomic imprinting is considered a special case of epigenetic modification. We propose that epigenetic modifications of a major predisposing gene in somatic tissues could cause differences in disease activity of psoriasis and could account for the often unpredictable clinical course the disease takes. PMID- 1632433 TI - Growth hormone deficiency and empty sella syndrome in a boy with dup(X) (q13.3--- q21.2). AB - A 2 8/12-year-old boy with severe growth failure and mental retardation was found to have a maternally derived tandem duplication of the long arm of X chromosome, dup(X) (q13.3----q21.2). Karyotypic interpretation was further confirmed in this patient by a double gene dose for red blood cell phosphoglycerate kinase. DNA replication study showed that the duplicated X chromosome was always late replicating in peripheral blood lymphocytes as well as in skin fibroblasts from the mother. Endocrine studies in the patient demonstrated growth hormone deficiency. Magnetic resonance imaging of the head then disclosed the empty sella syndrome. This appears to be the first report of a dup(Xq) patient associated with a growth hormone deficiency and the empty sella syndrome. We emphasize that duplication of the proximal Xq in males represents another microduplication syndrome (Thode-Leonard syndrome). PMID- 1632434 TI - del(18p) syndrome with complex tetralogy of Fallot in an infant with 45,X,t(Y;18)(q12;q11.2). AB - We report on an infant with multiple congenital anomalies, tetralogy of Fallot, and Karyotype 45,X,t(Y;18)(q12;11.2). The infant's anomalies are consistent with a del(18p) syndrome, except for the exceptional severity of the heart defect. PMID- 1632435 TI - Growth hormone therapy in achondroplasia. AB - A pilot study was carried out to examine the safety and efficacy of recombinant human growth hormone for growth-promoting therapy of achondroplasia. The data suggest that the agent in doses used to treat non-GH-deficient forms of short stature (0.3 mg/kg/wk) modestly increases overall height velocity in some children with achondroplasia. The effect was seen mainly in children with the lowest growth velocities prior to treatment. No untoward effects were noted. Several questions were raised that require further study. PMID- 1632436 TI - Unique karyotypes in two patients with Prader-Willi syndrome. AB - A physical disruption of the Prader-Willi syndrome (PWS) chromosome region is thought to cause PWS. We describe 2 girls with PWS phenotype, who had unique chromosome 15 abnormalities. The first patient showed mosaicism: 45,XX,t(15;15)(qter----p11.1::q11.200----qter)/46,XX,t(15;15)(qter----p1 1.1::q 11.200----qter), +mar. The band 15q11.2 apparently remained intact in the t(15;15) chromosome, and the mar chromosome was considered as r(15) (p11.1q11.1). The second patient had a karyotype of 47,XX,del(15)(q11.200----q11.207), +idic (15)(pter----q11.1::q11.1----pter). The complex breakage and reunion involving the 15q11.2 regions of the father's homologous chromosomes 15 at meiosis appeared to have resulted in the idic(15) and the del(15) chromosomes. These cytogenetic findings suggest that the PWS chromosome region may be localized on the very proximal portion of band 15q11.2. PMID- 1632437 TI - Interstitial deletion 8p21.3----p23.1 in a 6-year-old girl. AB - We present a 6-year-old mentally retarded girl. Chromosome analysis showed an interstitial deletion of chromosome 8; 46,XX,del(8) (pter----p23.1::p21.3--- qter). The proposita had normal activities of glutathione synthetase reductase (GSR) and factor VII. Parental chromosomes were normal. PMID- 1632438 TI - Short stature, Robin sequence, cleft mandible, pre/postaxial hand anomalies, and clubfoot: a new autosomal recessive syndrome. AB - We report on 5 unrelated Brazilian children with short stature, Robin sequence, cleft mandible, pre/postaxial hand anomalies, and clubfoot. Genetic aspects and phenotypic manifestations are compared with those of previous reports of acrofacial dysostoses and with other Robin sequence syndromes. We suspect that these patients present a previously undescribed autosomal recessive syndrome. PMID- 1632439 TI - Two distinct mutations in a single dystrophin gene: chance occurrence or premutation? AB - We report on a kindred segregating 2 distinct mutations of a dystrophin gene. DNA analysis showed that the second mutation, a deletion, arose in the same gene carrying the primary defect which produced a Becker phenotype in the affected males. The DNA data for this family are reported and the alternative explanations of chance occurrence and premutation are discussed to explain these unusual findings. PMID- 1632440 TI - beta-Glucuronidase deficiency as a cause of fetal hydrops. AB - Mucopolysaccharidosis type VII (MPS VII) was diagnosed in a case of severe fetal hydrops. beta-glucuronidase deficiency was demonstrated in the amniotic fluid, which was obtained at 25 weeks of gestation, and in the fibroblasts of the child, which were cultured after fetal death in the 26th week of gestation. In the amniotic fluid the two-dimensional electrophoresis pattern of glycosaminoglycans was in agreement with MPS VII. Based on these results, prenatal diagnosis could be offered to the couple for the next pregnancy. PMID- 1632441 TI - Glycogen storage disease type III with muscle involvement: reappraisal of phenotypic variability and prognosis. AB - A review of the case histories of 19 Japanese patients with enzymatically proven glycogen storage disease (GSD) III who developed muscular symptoms at various ages illustrates the phenotypic variability of this disease. There seem to be 4 subgroups of GSD III with muscle involvement according to the clinical symptoms. The first group of patients is characterized by the childhood onset of muscle weakness and hepatic disorders. The second group of patients develops muscular symptoms in adult years while the liver symptoms start in childhood. The third group includes the patients whose muscle weakness started in adult years long after liver symptoms in childhood had disappeared. The fourth group shows only muscular symptoms as adults without any sign or history of liver dysfunction since childhood. The prognosis for each subgroup seems to be different; however, none of them appears to be better than that for GSD I, as has been suggested previously. PMID- 1632442 TI - Ocular albinism in a male with del (6)(q13-q15): candidate region for autosomal recessive ocular albinism? AB - We describe a boy with an interstitial deletion of 6(q13-q15) and include "coarse" facial features, upslanting palpebral fissures, thin vermilion border of the upper lip, elongated philtrum, developmental delay, and profound hypotonia. The child's eye findings, pedigree, paucity of maternal ocular changes, and lack of melanin macroglobules in the skin suggest that this individual's phenotype is clinically similar to that of autosomal recessive ocular albinism. Though it is possible that this deletion and his ophthalmic disorder are coincidental, we postulate that the ocular albinism may be due to hemizygosity for a paternally derived ocular albinism gene located on chromosome 6 in the region q13-q15. This patient's deletion is secondary to a recombination of a maternal intrachromosomal inverted insertion of this region. Of the 7 reported 6q1 deletions, this is the only case that is due to a familial chromosome rearrangement. PMID- 1632443 TI - New skeletal dysplasia with unique brachydactyly. AB - We report on 2 male propositi, their mothers, and a maternal aunt with a new skeletal dysplasia associated with a unique pattern of digital malformation, variable mild short stature, and mild bowleg with proximal overgrowth of the fibula. The digital malformations comprise a pattern of brachydactyly which includes short, abducted thumbs, short index fingers, and markedly short, abducted great toes. The radiographic findings include hypoplastic thumbs and great toes with short first metacarpals and first metatarsals, absent distal phalanges of the index fingers and second toes, and coalescence of the carpal and tarsal bones. Radiographs of the long bones show mild metaphyseal and epiphyseal irregularity, tibial spurs, and relative elongation of the fibulae. The males are very similarly affected whereas the females show phenotypic variation and are generally less severely affected. The family histories from 2 fairly extensive pedigrees suggest X-linked dominant inheritance. PMID- 1632444 TI - Congenital absence of the vas deferens: recurrence in a family. AB - We report on 2 brothers with congenital absence of the vas deferens discovered in childhood during inguinal hernia repairs. The vas is absent unilaterally in one sib and bilaterally in the other. The unusual presentation of inguinal hernias in these children is discussed as well as mechanisms of inheritance and associated risk of renal anomalies. PMID- 1632445 TI - Segregation of three reciprocal translocations in the same family: t(3;4), t(5;10), and t(15;21). AB - A male infant with static antenatal encephalopathy and epilepsy was found to have a duplication of 5p12----5pter and deficiency of 10p13----10pter. Each of his parents was a carrier of a balanced reciprocal translocation. A third translocation was found in the maternal grandfather. The pedigree of each translocation and the segregation of parental reciprocal translocations are discussed. PMID- 1632446 TI - Identification of the origin of ring/marker chromosomes in patients with Ullrich Turner syndrome using X and Y specific alpha satellite DNA probes. AB - Fluorescent in situ hybridization (FISH) using X and Y chromosome-specific alpha satellite DNA probes hybridizing to loci DXZ1 and DYZ3 was performed to identify the origin of ring/marker chromosomes in 6 patients with Ullrich-Turner syndrome (UTS). All patients had a mosaic karyotype, 5 with 45,X/46,X,r(?) and one with 45,X/46,X,mar. We demonstrated that the marker/ring chromosome in each of these 6 patients originated from the X. A timely knowledge of the X or Y origin of ring and marker chromosomes can be crucial in genetic counseling and medical management since the presence of Y chromosome material in phenotypic females is known to increase the risk for developing gonadoblastoma. PMID- 1632447 TI - Dwarfism, rhizomelic limb shortness, and abnormal face: new short stature syndrome sharing some manifestations with Robinow syndrome. AB - We describe a child with short stature of prenatal onset, rhizomelic limb shortness affecting the upper limbs particularly, and an unusual face. She had frontal balding, mid-face hypoplasia, a small nose, macrostomia with down-turned corners of the mouth, gingival hypertrophy, and hypoplasia or absence of the clitoris. There was no gross modelling defect of the skeleton and the vertebral column was normal. Some of these manifestations overlap with those of Robinow syndrome. PMID- 1632448 TI - Charcot-Marie-Tooth neuropathy related to chromosome 1. AB - One family with documented male-to-male transmission of Charcot-Marie-Tooth (CMT) neuropathy was studied clinically and by genetic linkage. Patients had progressive distal weakness and atrophy, areflexia, and distal sensory loss, but early onset (before age 3 years) in all 5 cases, and phrenic nerve involvement in the propositus (a 39-year-old woman) requiring CPAP ventilator support during the night. Motor-nerve conduction velocities (MNCVs) were significantly slow, consistent with severe demyelinating neuropathy. Electromyography (EMG) data were normal. Two-point and multipoint linkage analyses strongly suggested the presence of a CMT gene on chromosome 1q. A maximum multipoint lod score of 2.70 was obtained at MUC1 (theta = 0), with the locus order centromere-MUC1-SPTA1-Fc gamma RII-AT3-telomere. Multipoint linkage analysis excluded the CMT locus from chromosome 17 markers in this family. PMID- 1632449 TI - New case of Bartsocas-Papas syndrome surviving at 20 months. AB - We report on patient with Bartsocas-Papas syndrome surviving at age 20 months. Similar to 7 previously reported families, this patient is of Mediterranean ancestry, pointing to clustering of the responsible mutant gene in Southern Europe. In 3 of the 11 Bartsocas-Papas syndrome patients described so far, including the present case, the condition has not been neonatally lethal. This suggests that about one-fourth of these patients could survive. This information is important for genetic counseling. PMID- 1632450 TI - Absent thumb, immune disorder, and congenital anemia presenting with hydrops fetalis. AB - A patient is described who presented with severe congenital anemia, hydrops fetalis, immune disorder, and absent thumbs. No toxic, infectious, or metabolic cause was found to explain these symptoms. Immunologic and cytogenetic studies excluded several syndromes that combine radial ray anomalies with hematological involvement. After careful study of the literature, it is concluded that the disorder described here represents a new syndrome that can be added to a growing list of hematological-radial syndromes. PMID- 1632451 TI - Heterogeneity in ataxia-telangiectasia: classical phenotype associated with intermediate cellular radiosensitivity. AB - We identified a subgroup of ataxia-telangiectasia (AT) patients (2 sibs and 1 unrelated case) characterized by typical clinical manifestations of the disease and cellular radiosensitivity intermediate between classical AT and normal subjects. Our data and a literature review of the intermediate radiosensitivity AT cases show that radioresistant DNA synthesis, cellular radiosensitivity (measured in terms of survival and chromosome breakage), and the clinical hallmarks behave independently. This raises a number of interesting questions about the correlation between radiobiological and clinical features, and about the nature of the AT gene(s). PMID- 1632452 TI - Prenatal diagnosis of the Pallister-Killian mosaic aneuploidy syndrome by CVS. AB - Prenatal cytogenetic analysis at 11 weeks of gestation revealed an abnormal karyotype 47,XX,+mar in all metaphases obtained from a chorionic villi sample after 24 h culture. Karyotyping of amniotic fluid cells in the second trimester showed mosaicism 47,XX,+i(12p)/46,XX with 10% aneuploid cells. The pregnancy was terminated at 20 weeks of gestation on the patient's request. The aborted fetus showed typical manifestations of the Pallister-Killian mosaic aneuploidy syndrome. The identity of the supernumerary isochromosome 12p was proven by LDH isozyme electrophoresis using cultured fibroblasts and by nonradioactive in situ hybridization using a biotinylated set of chromosome 12-specific DNA probes. PMID- 1632453 TI - Incidence of tuberous sclerosis in patients with cardiac rhabdomyoma. PMID- 1632454 TI - Lumping of CFC and Baraitser-Patton Noonan-like syndromes. PMID- 1632455 TI - Duty to disclose to family members in medical genetics. PMID- 1632456 TI - Basic fibroblast growth factor promotes proliferation of rat glomerular visceral epithelial cells in vitro. AB - Glomerular visceral epithelial cells (vGEC) play an important role in the synthesis of the glomerular basement membrane (GBM), and together with glomerular endothelial cells and the GBM, in glomerular ultrafiltration. Therefore clarification of the properties of vGEC is essential to investigations of glomerular morphology and function in both physiologic and pathologic conditions. This article demonstrates that basic fibroblast growth factor (bFGF) is mitogenic to vGEC in vitro. Its effect was found at concentrations as low as 1.25 ng/ml, and was synergistic with epidermal growth factor (EGF). In contrast, EGF by itself had no demonstrable mitogenic effect at concentrations of 1.25-100 ng/ml. In addition, mRNA for bFGF was identified in cultured vGEC by the method of reverse transcriptase polymerase chain reaction and the immunoreactivity of bFGF was found in GEC of the Sprague-Dawley rat kidney. These results suggest that bFGF stimulates the proliferation of vGEC in an autocrine manner in vivo. A unique relationship similar to that observed in endothelial cells may also exist among bFGF, vGEC, and the extracellular matrix (ECM). In a word, bFGF may be produced by vGEC and stored in the ECM, that is the GBM, and may be one factor that stimulates vGEC to proliferate when vGEC are injured and lost in vivo. PMID- 1632457 TI - Plasminogen activator inhibitor-1 deposition in the extracellular matrix of cultured human mesangial cells. AB - Human mesangial cells secrete tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1), the latter being secreted in large excess in vitro. We demonstrate that PAI-1 is a major component of the extracellular matrix of cultured human mesangial cells, where its deposition is dependent on cell density. By immunogold silver staining, epipolarization microscopy and dispersive X-ray spectrometry, we have shown that matrix associated PAI-1 is synthesized by spreading human mesangial cells, as indicated by the time-dependent accumulation of PAI-1 and the inhibitory effect of cycloheximide. Furthermore, by in situ hybridization, PAI-1 mRNA was detected in cultured mesangial cells. t-PA is present inside the cells, or at the cell surface, but is never associated with the extracellular matrix. Exogenous t-PA can remove matrix-associated PAI-1 without affecting cell adhesion. A similar effect was obtained by addition of urokinase-type plasminogen activator (u-PA) but not with fibrinolysis unrelated enzymes. In conclusion, PAI-1 is synthesized by human cultured mesangial cells and is deposited in the extracellular matrix by nonconfluent cells, whereas less PAI-1 is seen between confluent cells. This can explain the absence of detectable PAI-1 in normal human kidney biopsies. t-PA released by mesangial cells can bind and detach matrix PAI-1. PMID- 1632458 TI - Interleukin-6, but not interleukin-4, is expressed by Reed-Sternberg cells in Hodgkin's disease with or without histologic features of Castleman's disease. AB - Hodgkin's disease (HD) is a neoplastic disease that is characterized by unbalanced and/or unregulated cytokine production. Information accumulated in our own and other laboratories indicates that the cytokines interleukin-1 (IL-1), IL 5, IL-9, tumor necrosis factor-alpha (TNF-alpha), granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), and transforming growth factor-beta (TGF beta) are secreted by Hodgkin's and Reed-Sternberg (H-RS) cells. These and perhaps additional cytokines are likely to be responsible for the unique histopathologic and clinical alterations seen in patients with HD. In this study, we confirmed that IL-6 is produced by cultured H-RS cells as well as by H-RS cells in tissues. By using an enzyme-linked immunosorbent assay, we found that approximately 2 to 10 ng/ml of IL-6 was secreted by cultured H-RS cells (10(6) cells/ml). In tissues, we were able to immunolocalize IL-6 in the cytoplasm in 10 to 30% of H-RS cells by using rabbit polyclonal and mouse monoclonal anti-IL-6 antibodies. There was no correlation among the IL-6 staining intensity, number of H-RS cells stained, and the degree of plasma cell infiltration. However, in 3 of 17 cases studied, a large number (60%) of H-RS cells were positive for IL-6, and in these patients, abundant plasma cells were present. In one patient, the involved lymph node also showed histologic features similar to those of Castleman's disease. In this patient, we noted abundant IL-6 expression not only in H-RS cells, but also in most reactive histiocytes. The cultured H-RS cells did not express functional receptors for IL-6, and exogenously added IL-6 did not induce proliferation of these cells. We also conducted studies with specific anti IL-4 antibodies, which did not show IL-4 production by H-RS cells in both cultures and tissues. In tissues, only rare IL-4 positive lymphoid cells or dendritic cells were identified. Thus, the study demonstrated that adequate amounts of IL-6 are required for an abundant plasma cell reaction, and that an additional source of IL-6 from histiocytes is essential for the formation of Castleman's disease-like changes in lymph nodes involved by HD. Furthermore, IL-4 is not likely to be responsible for the T-lymphocyte reaction in tissues, by a mechanism distinct from that in T-cell-rich B-cell lymphomas. PMID- 1632459 TI - Immunopathology of glomerulonephritis associated with chronic woodchuck hepatitis virus infection in woodchucks (Marmota monax). AB - Retrospective analysis of necropsy findings of 705 woodchucks was performed to determine the prevalence and morphology of immune-mediated glomerulonephritis, its relationship to woodchuck hepatitis virus (WHV) infection, and the presence of major WHV antigens. Twenty-six woodchucks had glomerular lesions. Renal tissue of the 26 animals was evaluated histologically and immunohistochemically for immune-mediated glomerulonephritis. Of these 26 animals, immune-mediated glomerulonephritis was diagnosed in six, all of which were chronic WHV carriers. Membranous glomerulonephritis was identified in three animals, two of which also had mesangial proliferation. Host immunoglobulin was present within the mesangium and along capillary loops in all three. Woodchuck hepatitis virus core antigen (WHcAg) was present along capillary loops of two of these animals, one membranous and one mixed, and in the mesangium of all three. Woodchuck hepatitis virus surface antigen (WHsAg) deposition was similar to WHcAg deposition but was only present along capillaries in those animals with mixed nephritis. The remaining three animals had mesangial proliferation. WHsAg and host immunoglobulin deposition were predominately mesangial; WHcAg was not detected. Transmission electron microscopy showed thickening of the capillary loop basement membranes and subepithelial electron-dense deposits in animal one, and deposits in the mesangium in animal six. PMID- 1632460 TI - Detection of extracellular neutrophil elastase in hamster lungs after intratracheal instillation of E. coli lipopolysaccharide using a fluorogenic, elastase-specific, synthetic substrate. AB - Repeated intratracheal instillations of E. coli lipopolysaccharide (LPS) in hamster lungs cause an influx of polymorphonuclear leukocytes (PMNs) into the alveolar walls, with concomitant development of severe emphysema. It has been suggested that elastase, released by these PMNs, is involved in the development of emphysema. This study demonstrates the release of elastase from recruited PMNs in cryostat sections of hamster lungs, after being treated once, twice, or thrice with LPS, intratracheally. Elastase activity was visualized using two elastase specific synthetic substrates, to which a methoxynaphthylamine (MNA) group had been bound covalently. Liberated MNA, when made insoluble by coupling with 5 nitrosalicylaldehyde, fluoresces strongly. The authors observed that the interval between start of incubation and appearance of fluorescence and the intensity of fluorescence correlated with the number of LPS administrations. Fluorescence was observed to be located in or in close vicinity to alveolar walls. No fluorescence was observed in sections of untreated hamsters. Liberation of MNA from synthetic substrates was delayed strongly by the addition of a recombinant secretory leukocyte proteinase inhibitor or a substituted cephalosporin neutrophil elastase inhibitor. The authors conclude that LPS-mediated PMN influx into the lung is accompanied by release of elastase from these cells and speculate that this PMN elastase is involved in the development of LPS-mediated emphysema. PMID- 1632461 TI - Macrophage differentiation in atherosclerosis. An in situ immunohistochemical analysis in humans. AB - The differentiation of macrophages present in diffuse intimal thickening, fatty streaks, and atheromatous plaques, was analyzed with immunohistochemical methods, using segments of aorta, coronary, and carotid arteries obtained at autopsy. Various differentiation antigens were studied with the monoclonal antibodies anti HLA-DR, EBM-11, Leu M3, OKM1, and OKM5. Adjacent sections were stained for lipids (oil red O) and lysosomal activity (acid phosphatase). Almost all macrophages identified with the pan-macrophage antibody EBM-11, also stained with the anti HLA-DR antibody. Diffuse intimal thickening showed a predominance of Leu M3+ cells; fatty streaks also showed OKM1+ and OKM5+ macrophages. Classical atheromatous plaques showed a gradual shift in phenotypic expression towards the center of the lesion. Cells in the superficial layers were positive only with Leu M3, deeper localized cells showed double expression of Leu M3 and OKM1 or double expression of OKM1 and OKM5. Cells that were localized adjacent to the atheromatous debris stained only with OKM5. The phenotypic changes occurred in parallel with an increase in both fat uptake and lysosomal activity of the macrophages. This shift in phenotypic expression suggests a process of differentiation and maturation of the macrophages involved. The results indicate that macrophages within the arterial intima are activated and mature towards cells that express receptors for adhesion proteins and complement during the development of atherosclerotic plaques. This may imply that the macrophages involved in lipid metabolism also have a potential to act as effector cells in a chronic inflammatory process, and thus, may contribute to the progression of an atherosclerotic plaque. Functional studies of macrophage subpopulations are needed to verify this hypothesis. PMID- 1632462 TI - Chronic hemodynamic unloading regulates the morphologic development of newborn mouse hearts transplanted into the ear of isogeneic adult mice. AB - The morphologic development of newborn mouse hearts transplanted into the pinna of the ears of isogeneic adult mice was assessed in comparison to in situ ventricular myocardium of recipients. The grafted hearts became vascularized from the auricular artery at the base of the ear, and although these preparations appeared not to be intrinsically innervated, most of them showed grossly visible pulsatile activity. Since they were not subjected to hemodynamic load due to working against a pressure gradient, this technique provided an interesting experimental model for studies on the growth of chronically unloaded tissue. The ultrastructure of the myocardium from neonatal mouse hearts, which were fixed immediately after dissection, revealed no differences in comparison to previously published observations. By 2 months, there was virtually no change in the myocardial cell size as compared with newborn mouse cardiac tissue. The heterotopic hearts showed a mature ultrastructural appearance, with parallel bands of myofibrils alternating with rows of mitochondria and differentiated intercalated discs comparable to in situ myocardium. The interstitial space was widened due to fibrous tissue, with activated fibroblasts and a few mononuclear cells. In contrast, by 6 months after transplantation, the heterotopic myocardium showed a dispersion of the measured cell diameter of myocytes, with atrophy of a certain population of cells and hypertrophy in others; nevertheless, the mean cell diameter was similar to that observed in 2-month grafts. The myocytes showed significant dissociation from each other in fibrous tissue and a cellular infiltrate composed predominantly of mononuclear cells, and greater variability of the parallel arrangement of cells. They often contained myofibrils coursing in different directions rather than in parallel. Normal-sized or predominantly atrophic degenerated myocytes, characterized by a wide variety of ultrastructural alterations, were present. By 12 months after transplantation, the myocytes of heterotopic hearts were smaller in size in comparison to those after 2 or 6 months. The graft cells were separated from each other by fibrous tissue and mononuclear cells and were not aligned in parallel within the tissue; often, they appeared to have lost their connections with adjacent cells. The myofibrils within cells were strikingly disorganized, coursing in different directions. Severely degenerated myocytes were commonly seen. These results, without precluding the possible role of neural and hormonal stimuli, clearly indicate that hemodynamic work load regulates the developmental growth of newborn mouse heart transplanted into the pinna of the ear of isogeneic adult recipient mice. In other words, the mass of cardiac tissue would be adjusted to meet the prevailing hemodynamic demands.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1632463 TI - The bcl-2 gene translocation is undetectable in Hodgkin's disease by Southern blot hybridization and polymerase chain reaction. AB - B-cell associated antigens are frequently expressed by the Reed-Sternberg (RS) cells of lymphocyte predominance (LP) Hodgkin's disease (HD) and are sometimes expressed by those of nodular sclerosis (NS) and mixed cellularity (MC) HD. Clonal immunoglobulin gene rearrangements have been detected in some HD cases as well. These findings suggest that at least some cases of HD may be of B-cell derivation. Rearrangements of the bcl-2 gene, associated with the t(14;18)(q32;q21) are present in more than 75% of follicular and 30% of diffuse lymphomas of B-cell origin, suggesting that this translocation plays an important role in B-cell lymphomagenesis. In this study, we investigated 34 cases of HD (10 LP, 14 NS, and 10 MC) for bcl-2 gene rearrangements to determine if this B-cell lymphoma-associated translocation also plays a role in the pathogenesis of HD. The cases of HD were analyzed by Southern blot hybridization, using DNA probes that detect the major and minor breakpoint cluster regions and a 5'bcl-2 breakpoint region recently cloned and found to be involved in B-cell chronic lymphocytic leukemia, and by the polymerase chain reaction (PCR), using oligonucleotides capable of amplifying and detecting the major breakpoint region (mbr) and minor cluster region (mcr) breakpoint regions in t(14;18). bcl-2 translocations were not detected in any of the 34 cases of HD by Southern blot hybridization or by PCR. This is in spite of the fact that RS cells expressing B cell-associated antigen CD20 were detectable in 7/8 cases of LP HD and 6/24 cases of NS and MC HD with monoclonal antibody L26. Therefore, these results indicate that the bcl-2 gene translocation does not play an important role in the pathogenesis of HD and did not provide evidence for the B-cell origin of HD. PMID- 1632464 TI - Flow cytometric analysis of pulmonary fluids and cells for the detection of malignancies. AB - Cells from a pulmonary or bronchial origin were analyzed with flow cytometry to assess the sensitivity and specificity of this method in diagnosing malignancy. In all instances, cells submitted for flow cytometry analysis were excess cells from specimens submitted for routine cytology. Less than 3% of all samples were rejected for insufficient material. Overall sensitivity from all sources was 86%, specificity 96%. Although cytology results were the standard for determining accuracy of flow cytometry, in a few patients cytology appeared normal and initial evidence for malignancy was obtained from flow cytometry. For this reason, flow cytometry may be a valuable adjunctive technology in the diagnosis of malignancy. PMID- 1632465 TI - In vitro spontaneous synthesis of beta 2-microglobulin amyloid fibrils in peripheral blood mononuclear cell culture. AB - beta 2-microglobulin-related amyloidosis (A beta 2M), in long-term dialysis patients, is a new and frequent complication for which the pathogenesis remains unknown. The authors documented, by light and high resolution electron microscopy, the spontaneous polymerization of beta 2-microglobulin to amyloid fibrils in mononuclear cell culture supernatants from dialysis patients. These data provide significant information about the pathogenesis of dialysis amyloidosis, revealing an unusual and different fibrillogenic mechanism for beta 2-microglobulin and dialysis-amyloidosis than for other forms of amyloidosis. beta 2-microglobulin does not appear to require a proteolytic process before polymerization into amyloid fibrils and deposits. This study represents the first cell culture system in which beta 2-microglobulin amyloid fibrils have been spontaneously created. PMID- 1632466 TI - Beta amyloid is focally deposited within the outer basement membrane in the amyloid angiopathy of Alzheimer's disease. An immunoelectron microscopic study. AB - The fine structure of cerebral amyloid angiopathy, especially in small and presumably early deposits, was examined by immunolabeling of the beta/A4 protein in semithin and ultrathin sections from brains with Alzheimer's disease. The following findings emerged: 1) in large leptomeningeal arteries, small, focal amyloid deposits appear to consist of clusters of delicate (approximately 8 nm diameter) amyloid fibrils, not previously described, in the outermost part of the basement membrane (BM) at the media-adventitia junction; 2) in small leptomeningeal arteries and perforating cortical arterioles, small foci of delicate amyloid fibrils were observed within the BM. They appeared mostly in the outer portion of the BM, around intact smooth muscle cells, rather than in the subendothelial region. In larger and presumably more advanced deposits, coarse amyloid fibrils (approximately 10 nm) occupied the abluminal BM, and adjacent smooth muscle cells showed degeneration; and 3) in capillaries, small amounts of delicate (approximately 8 nm) amyloid fibrils, not previously described, were seen within the BM in the smallest discernible deposits. The BM at these sites was abnormally folded and layered. In larger deposits, amyloid fibrils appeared to extravasate from the outer BM of the capillary into the neuropil and were surrounded by astrocytic foot processes and/or microglia. Our results suggest that vascular amyloid fibrils may first be formed within the abluminal vascular BM, that is, outside of cells. The BM may trap degradative intermediates of the amyloid precursor protein that contain the beta/A4 region, and local proteases may then cleave them further to yield amyloidogenic fragments. PMID- 1632467 TI - Overexpression of p53 protein in basal cell carcinomas of human skin. AB - Basal cell carcinoma (BCC) of the skin is the most common human cancer, but its molecular-genetic pathogenesis is unclear. In many other types of cancer, mutations of the tumor-suppressor gene p53 occur frequently and may lead to overexpression of a long-lived mutant form of p53 protein. In this study, overexpression of p53 protein was detected immunohistochemically in 30 (83%) of 36 specimens of BCC of the head and neck. The same regions of tumor typically were reactive both with a monoclonal antibody (PAb240) specific for the mutant protein and with one (PAb1801) directed against an epitope common to both wild type and mutant p53 protein. Keratinocytes of chronically sun-exposed epidermis adjacent to BCCs also focally overexpressed p53 protein in the majority of cases, whereas those of sun-protected buttock skin did not. Mutation of p53 may form an important part of the pathogenetic sequence in a majority of cases of BCC. PMID- 1632468 TI - The NIH-3 immunodeficient mouse is a model for Lyme borreliosis myositis and carditis. AB - Experimental infection of immunodeficient NIH-3 (N:NIH-bg-nu-xid) mice with Borrelia burgdorferi was found to result in multisystem histopathologic lesions. In addition to T-cell deficiency due to the nude mutation, these mice have an x linked defect affecting the B-cell maturation and the beige mutation resulting in the absence of NK cells. NIH-3 mice were susceptible to progressive infection with B. burgdorferi resulting in pancarditis, synovitis, and skeletal interstitial myositis whereas controls remained normal. Cardiomyopathy was characterized by inflammatory mononuclear infiltration and fibrillar necrosis. Synovial hyperplasia and inflammation were seen in the tibiotarsal and ulna carpal joints. Advanced myositis was observed in peripheral skeletal muscle. Gastrointestinal submucosa, heart, and skeletal muscle were heavily colonized with B. burgdorferi. This mouse is proposed as a model for Lyme borreliosis carditis, synovitis, and myositis. PMID- 1632469 TI - Characterization and immunohistochemical localization of alpha 2-macroglobulin receptor (low-density lipoprotein receptor-related protein) in human brain. AB - Proteinase inhibitors have been implicated in brain development and in degenerative processes such as Alzheimer's disease. Low-density lipoprotein receptor-related protein (LRP) is a multifunctional cell-surface receptor that binds activated forms of the proteinase inhibitor, alpha 2-macroglobulin (alpha 2M) and apolipoprotein E. Solubilized plasma membranes of human cerebral cortical gray matter were subjected to affinity chromatography on alpha 2M-methylamine sepharose. A single receptor was purified; this protein was LRP as determined by molecular mass, peptide structure, and immunoreactivity with monoclonal and polyclonal antibodies. In adult human brain, LRP immunoreactivity was abundant on neuronal cell bodies and proximal processes. Other cells within the neuropil, including glia and microvascular cells (endothelium and pericytes), were immunonegative. Weak LRP immunoreactivity was identified in a perivascular pattern corresponding to the location of astrocytic foot processes. The distribution of LRP in the central nervous system is consistent with the potential function of this receptor in the regulation of proteinase activity, cytokine activity, and cholesterol metabolism. PMID- 1632470 TI - Follicular colonization in thyroid lymphoma. AB - The presence of neoplastic (light chain restricted) B-cell follicles in low-grade B-cell gastrointestinal (GI) lymphoma of mucosa-associated lymphoid tissue (MALT) has been explained on the basis of specific colonization of reactive follicles by centrocyte-like (CCL) cells. Low-grade B-cell thyroid lymphomas have been included in the category of MALT lymphoma, but the frequent presence of a follicular pattern in these tumors has contributed to the view that they are follicle center cell (FCC) tumors. We have reviewed the histology and investigated the phenotype and genotype of nine cases of primary low-grade B-cell lymphoma of the thyroid, all of which were distinguished by a predominantly follicular pattern. All cases also demonstrated features of MALT lymphoma, including CCL cells and lymphoepithelial lesions. The appearances and immunohistology of the follicles were those of follicular colonization as described in GI MALT lymphoma rather than FCC follicular lymphoma. The predominant pattern of follicular colonization was replacement of the follicle center by slightly enlarged CCL cells that showed a strikingly high proliferation rate. No evidence of the t(14;18) translocation was found in any case, using the polymerase chain reaction (PCR) on DNA extracted from fresh (n = 1) or paraffin embedded (n = 9) tissue. These findings argue against a FCC lineage for primary thyroid lymphomas and support their inclusion in the MALT category. PMID- 1632471 TI - Experimental pneumococcal meningitis causes central nervous system pathology without inducing the 72-kd heat shock protein. AB - We examined whether experimental pneumococcal meningitis induced the 72-kd heat shock protein (HSP72), a sensitive marker of neuronal stress in other models of central nervous system (CNS) injury. Brain injury was characterized by vasculitis, cerebritis, and abscess formation in the cortex of infected animals. The extent of these changes correlated with the size of the inoculum (P less than 0.003) and with pathophysiologic parameters of disease severity, i.e., cerebrospinal fluid (CSF) lactate (r = 0.61, P less than 0.0001) and CSF glucose concentrations (r = -0.55, P less than 0.0001). Despite the presence of numerous cortical regions having morphologic evidence of injury, HSP72 was not detected in most animals. When present, only rare neurons were HSP72 positive. Western blot analysis of brain samples confirmed the paucity of HSP72 induction. The lack of neuronal HSP72 expression in this model suggests that at least some of the events leading to neuronal injury in meningitis are unique, when compared with CNS diseases associated with HSP72 induction. PMID- 1632472 TI - Diarrheal disease as a cause of malnutrition. AB - Although long associated with infectious diseases, malnutrition is recognized as a major effect of specific infections, especially those of the gastrointestinal tract. Synergistic exacerbation of infections and nutritional deficiency commonly begin with weaning, where the impact of repeated infections and possible monocyte mediator release may have an even greater effect on malnutrition of young children than that of deficient diets in many areas. Reviewed here are the detailed host alterations seen with specific enteric infections that lead to malnutrition. These include mucosal dysfunction, systemic metabolic responses, impaired intake, digestion and absorption, nutrient losses, altered immune responses, and ultimately, impaired growth, development, and nutrition. The tremendous health impact of diarrhea on both morbidity and mortality in many developing areas must be recognized and controlled along with correction of food shortages in order to improve the nutrition, growth, and survival of impoverished children. PMID- 1632473 TI - Tumor necrosis factor in the malnutrition (cachexia) of infection and cancer. AB - This review presents a history of tumor necrosis factor, considers the biology of this pleiotropic mediator, and summarizes the evidence that implicates it as a mediator of cachexia. PMID- 1632474 TI - Diarrhea as a cause and an effect of malnutrition: diarrhea prevents catch-up growth and malnutrition increases diarrhea frequency and duration. AB - Diarrhea and malnutrition, alone or together, constitute major causes of morbidity and mortality among children throughout the tropical world. Data from northeast Brazil, taken with numerous other studies, clearly show that diarrhea is both a cause and an effect of malnutrition. Diarrheal illnesses impair weight as well as height gains, with the greatest effects being seen with recurrent illnesses, which reduce the critical catch-up growth that otherwise occurs after diarrheal illnesses or severe malnutrition. Malnutrition (whether assessed by impaired weight or height for age) leads to increased frequencies and durations of diarrheal illnesses, with a 37% increase in frequency and a 73% increase in duration accounting for a doubling of the diarrhea burden (days of diarrhea) in malnourished children. A multi-pronged approach focusing on those with prolonged diarrhea and severe malnutrition is suggested. PMID- 1632475 TI - Nutrition and infection. PMID- 1632476 TI - Visceral leishmaniasis: a model for infection-induced cachexia. AB - Parasitic infections and malnutrition coexist in many tropical and subtropical areas. Studies of Leishmania donovani and of experimentally infected Syrian hamsters have provided important insights into the complex interrelationships between malnutrition and this parasitic disease. Malnutrition, which adversely affects cell-mediated immunity, is associated with the development of visceral leishmaniasis (kala-azar) in children living in endemic areas. In turn, L. donovani can cause wasting as well as hepatosplenomegaly, fever, and anemia. Syrian hamsters infected with L. donovani develop a disease that is comparable to that of humans with kala-azar. Weight loss in infected hamsters is associated with splenic macrophage secretion of potentially catabolic cytokines as measured by the D10.G4.1 assay for interleukin-1 and the L929 cytotoxicity assay for tumor necrosis factor/cachectin. Although decreased food intake contributes to wasting in infected hamsters, studies of skeletal muscle function indicate that it is not the sole factor. Leishmania donovani-infected hamsters have also been used to study drugs with the potential to prevent or reverse cachexia. PMID- 1632477 TI - Genetic control of eosinophilia in guinea pig strains inbred for high or low bronchial allergic reactivity. AB - Development of eosinophilia was studied in four strains of guinea pigs (gp), selectively bred for either high or low respiratory anaphylactic reactivity. One high-asthma strain (IMM/S 209) and one low-asthma strain (IMM/R 203) developed spontaneous high blood eosinophilia. The 2 other gp strains - one high-asthma strain (IMM/S 740) and one low-asthma strain (IMM/R 201-16) - maintained normal low levels of eosinophilic granulocytes (eos). The levels of eos in various tissues showed similar differences between the gp strains. Following immunization with ovalbumin/Al(OH)3 the levels of blood eos increased significantly only in gp of strain 209. The blood eos levels in gp of all 4 strains decreased significantly following immunization with ovalbumin in Freund's complete adjuvant (FCA). PMID- 1632478 TI - Detection of allergens in a cat pelt extract. AB - Allergenic components of cat pelt extract fractionated by SDS-polyacrylamide gel electrophoresis (PAGE) and transferred to nitrocellulose membranes were identified using sera from 15 allergic patients who showed positive skin test and RAST to cat extract. Two components showed the highest IgE-binding frequency; 14 kD (being recognized by 86% of the sera examined) and 29 kD (73% of the sera tested). Both components were purified by electroelution and subjected to RAST inhibition assays. The 29 kD fraction was able to bind specific IgE to D. pteronyssinus and inhibited a RAST assay of 29 kD component (Der p I) purified from a D. pteronyssinus extract. These results could explain the finding of positive skin test with some commercial cat allergen solutions in patients with D. pteronyssinus allergy. PMID- 1632479 TI - A clinical index: a new method to assess efficacy of allergen immunotherapy. AB - Assessment of efficacy in immunotherapy trials is difficult: a number of parameters can be measured; these may give conflicting results and it is not clear which best represents the clinical state. We therefore derived a Clinical Index (CI), by combining five individual parameters-diary card symptom score, visual analogue symptom score, drug score, nasal challenge and skin prick test-by rank analysis. The CI has been used to express the results in a trial of house dust mite (D. pteronyssinus) immunotherapy for allergic rhinitis, comparing two active treatments, Pharmalgen and Allpyral, with placebo. The derived index correlated well with all parameters measured. Correlations between the five individual parameters were variable: with the exception of the skin test, good correlations were seen, each parameter correlating with two or three of the others, but the visual analogue showed the closest association with other parameters. Results from a single parameter taken alone could be misleading, e.g. in the Allpyral group, nasal challenge improved significantly, but symptoms assessed either by visual analogue or diary card score did not. The CI showed significant improvement in the Pharmalgen group but not in the Allpyral group. The CI gave a more reliable measure of outcome than individual parameters. PMID- 1632480 TI - Anaphylactic shock after skin test with phytohaemoagglutinin. AB - A young woman (26 years old), with gastrointestinal candidosis of 8 months duration, was hospitalized in our department to study her cell immunity. Five minutes after an id injection of PHA (bactophytohaemoagglutinin M, Difco, 1 mg), mix monilieae, mix tricophyton and PPD Berna, she showed an extensive wheal and flare reaction in the PHA injection area, eyelid oedema and respiratory distress. In spite of adrenaline, corticosteroid and antihistamine drug administration, the patient collapsed and was admitted to the resuscitation department, where she quickly recovered. In the following days, the patient underwent immune and allergy testing: 1) total Ige immuno-enzymatic assay: 72 KU/1; 2) specific IgE and IgE immuno-enzymatic assay for Candida: negative; 3) in vitro lymphocyte transformation test (thymidine 2-C14) with PHA Difco was positive. This finding and the positivity of the id injection with PHA could indicate an allergic type I immunoreaction, the description of which we have not found in the international literature (the presence of IgG STS cannot be totally excluded). PMID- 1632481 TI - Pathophysiology of itching in urticaria and atopic dermatitis. PMID- 1632482 TI - Presence of viable mould propagules in indoor air in relation to house damp and outdoor air. AB - The presence of viable mould propagules in indoor air was investigated using the N6-Andersen sampler in combination with DG18-agar, in relation to house damp (characterized with a checklist) and in relation to the presence of moulds in outdoor air. The first part of the study was conducted in 46 houses in the autumn of 1987, the second part in 84 houses in May 1989. Further, in the second part, the results obtained with settlement plates (OPD) were compared with those obtained with the N6-Andersen sampler. The number of CFU/m3 in the indoor and outdoor air varied widely. A large variety of mould genera and species was isolated. Species of Cladosporium, Penicillium and Wallemia predominated. The variability in time was high and the reproducibility of the measurements in terms of CFU/m3 and of species isolated was only moderate. The low predictive value of these measurements limits their use in epidemiological studies of the relationship between exposure to moulds and respiratory symptoms. Overall, the geometric mean concentration was somewhat higher outdoors than indoors. However, the clear differences found between the number of CFU/m3 belonging to different mould species in in- and outdoor air show that the presence of viable mould propagules in indoor air is not simply a reflection of the presence of moulds in outdoor air. The presence of moulds in indoor air was only weakly related to house damp as characterized by the checklist. High, statistically significant correlations were found between the CFU yield obtained with the OPD and the CFU/m3 yield obtained with the N6-Andersen sampler.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632483 TI - Study of the allergenic fractions of latex. AB - Two latex (Hevea brasiliensis) raw materials, one from the cytosolic fraction, the other from the total natural latex have been characterised by immunoblotting techniques. The two latex fractions A and B were studied by immunoprints using eight sera from patients who were allergic to latex. They gave different profiles though there were also allergens of common molecular weights (60, 35, 30, 25, 20, 18, 15, and 10 kD). This study confirms the importance of allergic reactions to latex, that may in some patients cause anaphylactic shock. PMID- 1632484 TI - Cytogenetic approaches to genome mapping. PMID- 1632485 TI - Determination of the in vivo redox status of cysteine, cysteinylglycine, homocysteine, and glutathione in human plasma. AB - An assay that measures the reduced, oxidized, and protein-bound forms of cysteine, cysteinylglycine, homocysteine, and glutathione in human plasma is described. Oxidized and protein-bound thiols are converted to their reduced counterparts by the use of NaBH4, and, following derivatization with monobromobimane (mBrB), the thiol-bimane adducts are quantified by reversed-phase ion-pair liquid chromatography and fluorescence detection. The presence of 50 microM dithioerythritol provides linearity of the standard curves at very low thiol concentrations. Selective determination of the oxidized forms was accomplished by blocking free sulfhydryl groups with N-ethylmaleimide (NEM) and excess NEM is inactivated by the subsequent addition of NaBH4. The reduced forms of the thiols in plasma were trapped with minimal oxidation by derivatizing blood samples at the time of collection. This was attained by drawing blood directly into tubes containing isotonic solutions of mBrB or NEM. The assay is sufficiently sensitive (less than 2 pmol) to detect the various forms of the four thiol compounds in human plasma. The analytical recovery of cysteine, cysteinylglycine, homocysteine, and glutathione was close to 100%, and the within day precision corresponded to a coefficient of variation of 7, 8, 6, and 7%, respectively. The assay has been used to determine the various forms of the four thiol compounds in human plasma. PMID- 1632486 TI - Assay of thiols and disulfides based on the reversibility of N-ethylmaleimide alkylation of thiols combined with electrolysis. AB - A simple and specific method for analyzing thiols and disulfides on the basis of the reversibility of N-ethylmaleimide (NEM) alkylation of thiols is described. When the adduct of NEM and glutathione (GSH) was electrolyzed at neutral pH, all of the GSH was recovered. When the adduct was exposed to pH 11.0 for 15 min at 30 degrees C before electrolysis, GSH was not detected. The same behavior was observed after protein thiols reacted with NEM. This pH-dependent production of thiol from the adduct was used to assay GSH and oxidized glutathione in yeast cells, to assay sulfhydryl groups and disulfide bonds in authentic proteins, and to protect thiols from oxidation during enzymatic digestion of protein. This method is useful for assay of thiols and disulfides of both small and large molecules and can be used to identify labile thiols in biological samples that are oxidized during extraction procedures. PMID- 1632487 TI - A modified colorimetric method for the determination of orthophosphate in the presence of high ATP concentrations. AB - We describe a modified colorimetric method that quantitates inorganic phosphate linearly up to 60 nmol, with high stability of the developed color and with a low interference by ATP concentration (up to 30 mM). This method is very suitable for use in ATPase enzymatic assays, especially with enzymes that have low specific activities and (or) high Km values for ATP. PMID- 1632488 TI - A gel electrophoresis assay for phytochelatins. AB - Phytochelatins are metal-binding peptides produced by higher plants and some fungi in response to heavy metal exposure. Established methods for analyzing cell free extracts for the presence of phytochelatins include gel-filtration chromatography and HPLC. We have developed a nondenaturing polyacrylamide gel electrophoresis assay for phytochelatins that combines a small sample size with detection via metal binding. This assay can be used for the measurement of the relative affinity of phytochelatins for a variety of metal and semimetal ions. PMID- 1632489 TI - Xerographic paper as a transfer medium for western blots: quantification of bovine alpha S1-casein by western blot. AB - We have found that xerographic paper (regular photocopy or laser printer paper) can be used as a transfer medium for protein blots for the immunodetection of low concentrations (a few nanograms) of bovine alpha S1-casein. With paper blotting, we could detect the protein with three times more sensitivity than with polyvinylidene difluoride. Blotting was achieved by transfer from sodium dodecyl sulfate-polyacrylamide gel electrophoresis to the methanol-wet paper. The blot was incubated with chicken anti-casein antibodies, sequentially peroxidase labeled rabbit anti-chicken antibodies, and diaminobenzidine substrate. The blots were directly scanned and the pixel intensity of the band areas was integrated. An analysis of the scanned blots showed that the log of protein concentration was linearly related with the square root of an integrated pixel intensity (r2 greater than 0.96). This linear relationship was observed in a wide range of protein concentration from 5 ng to 15 micrograms. The coefficients of variation were 12.4% for intraassay and 15.7% for interassay. This new analytical procedure can be applied to estimate the concentration of proteins by immunological blotting. PMID- 1632490 TI - Simultaneous determination of 3-hydroxyanthranilic and cinnabarinic acid by high performance liquid chromatography with photometric or electrochemical detection. AB - A convenient and rapid method for the simultaneous determination by HPLC of 3 hydroxyanthranilic acid and the dimer derived by its oxidation, cinnabarinic acid, is described. Buffers or biological samples containing these two Trp metabolites were acidified to pH 2.0 and extracted with ethyl acetate with recoveries of 96.5 +/- 0.5 and 93.4 +/- 3.7% for 3-hydroxyanthranilic and cinnabarinic acid, respectively. The two compounds were separated on a reversed phase (C18) column combined with ion-pair chromatography and detected photometrically or electrochemically. The method was applied successfully to biological systems in which formation of either 3-hydroxyanthranilic or cinnabarinic acid had been described previously. Thus, interferon-gamma-treated human peripheral blood mononuclear cells formed and released significant amounts of 3-hydroxyanthranilic acid into the culture medium and mouse liver nuclear fraction possessed high "cinnabarinic acid synthase" activity. In contrast, addition of 3-hydroxyanthranilic acid to human erythrocytes resulted in only marginal formation of cinnabarinic acid. We conclude that the method described is specific, sensitive, and suitable for the detection of the two Trp metabolites in biological systems. PMID- 1632491 TI - Affinity-mediated modification of electrical charge on a cell surface: a new approach to the affinity partitioning of biological particles. AB - Polylysine has been covalently bound to human transferrin in a 1:1 molar ratio over a disulfide bond that can be easily split by reducing agents such as dithiothreitol. The association constant for the binding of the transferrin polylysine derivative to transferrin receptors present on rat erythroblasts and the number of binding sites were identical to the corresponding values found for native transferrin. The incubation of the cells with transferrin-polylysine affected the partitioning of erythroblasts in a charge-sensitive aqueous two phase system containing Dextran and polyethylene glycol. The polylysine part introduced a nonspecific influence on the partitioning that could be eliminated by preincubation of the cells with an excess of sialic acid. The partition ratio, G, of the erythroblasts changed with a factor of 1.9 for each set of 100,000 polylysine chains attached per cell. PMID- 1632492 TI - An indirect-labeling procedure for the study of specific interactions of proteins with DNA. AB - A semiquantitative and reproducible indirect-labeling procedure for the study of specific protein/DNA interactions using nitrocellulose-filter-immobilized proteins and linear or superhelical DNA molecules is reported. Proteins were immobilized on nitrocellulose filters either by direct dotting or by electrotransfer from polyacrylamide electrophoretic gels. After incubation with the respective DNA (linear restriction fragments or closed circular recombinant DNA plasmids) the paper strips were washed, and specifically bound DNA was denatured by alkali and detected by hybridization with 32P-nick-translated DNA. The quantitation of the reaction was performed by scanning of the autoradiograms of the radioactive spots and determination of the area under the respective peaks. The intensity of the radioactive spots was proportional to the amount of protein present in the dot. The sensitivity of the assay depends primarily on the affinity of the respective DNA to the protein and in the case of mouse liver histone H1AB/mouse alpha-globin gene approximately 50 ng of protein per dot was enough for determination. PMID- 1632494 TI - Automated solid-phase peptide synthesis: use of 2-(1H-benzotriazol-1-yl)-1,1,3,3 tetramethyluronium tetrafluoroborate for coupling of tert-butyloxycarbonyl amino acids. AB - 2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) has been adapted for use as a coupling reagent for tert-butyloxycarbonyl (Boc) amino acids in automated solid-phase peptide synthesis. When compared to the existing preformed symmetrical anhydride procedure employing dicyclohexyl-carbodiimide (DCC), the use of TBTU in the presence of 1-hydroxybenzotriazole (HOBt) provides a more efficient coupling procedure for Boc-amino acid derivatives. Overall cycle times using TBTU/HOBt coupling reagents (30 min) compare favorably to those of the DCC-mediated procedure (approx 65 min). Dimethylformamide can be used as the sole solvent for both activation and coupling reactions. Implementation of TBTU/HOBt coupling conditions does not require replumbing of any lines of the Applied Biosystems Model 430A instrument and necessitates changes to only three reagent bottle positions. The variable coupling efficiencies of Boc-asparagine following activation with TBTU/HOBt (as low as 89%) can be overcome by protection of the amide function of Boc-asparagine with the 9-xanthyl group. Examples of the synthesis and characterization of a number of peptides ranging in length from 13 to 29 residues are given. PMID- 1632493 TI - Characterization and quantification of diadenosine hexaphosphate in chromaffin cells: granular storage and secretagogue-induced release. AB - The presence of diadenosine hexaphosphate (Ap6A) in chromaffin cells is described. The characterization of Ap6A has been accomplished by HPLC techniques, using three different elution conditions, rechromatography, and coelution with standards. Treatment with phosphodiesterase from Crotalus durissus produced AMP and adenosine pentaphosphate. The HPLC techniques described allowed the quantification of Ap6A in the picomole range. Chromaffin granules store Ap6A in a quantity of 48.5 +/- 9.7 nmol/mg protein, with a molar ratio ATP/Ap6A of 27. In chromaffin cells the Ap6A value was 1.46 +/- 0.32 nmol/10(6) cells. Diadenosine hexaphosphate was released from chromaffin cells by the action of carbachol and a value of 64 +/- 15 pmol/10(6) cells was obtained, which represents 4-5% of the total cellular content. PMID- 1632495 TI - Use of delta-(alpha-aminoadipoyl) chromogenic amides in screening for aminoadipoyl amidohydrolases. AB - The synthesis of delta-(alpha-aminoadipoyl) aromatic amides and their use in screening for enzymes able to cleave delta-(alpha-aminoadipoyl) residues off the synthetic amides and cephalosporin C are described. A number of commercially available proteases and peptidases were not active with delta-(alpha aminoadipoyl) chromogenic amides. Also, most tested microbial strains known to produce acylases did not hydrolyze these compounds. Only one microbial strain, Xanthomonas maltophila, had an appreciable activity toward the racemic form of chromogenic substrates. Activity measured in crude extracts from Xanthomonas cells indicated that this bacterium produces predominantly L-specific aminoadipoyl amidohydrolase and gamma-glutamyl hydrolase. A low level of cephalosporin C and glutaryl-cephalosporin acylase activities was also found. PMID- 1632496 TI - Extending CD spectra of proteins to 168 nm improves the analysis for secondary structures. AB - The CD spectra for 10 proteins with known secondary structure have been extended from 178 to 168 nm. Combined with the data for 6 other proteins investigated previously, this produces a basis set of 16 proteins, which can be used to analyze CD spectra for secondary structure. Extending the spectra adds another CD band to the data and increases the information content from the equivalent of five to six. Analyzing the CD for each of the 16 proteins in the basis set with the 15 other proteins shows a modest improvement in the prediction of secondary structure with the extended CD spectra. PMID- 1632497 TI - High-performance liquid chromatographic determination of catecholamines and their precursor and metabolites in human urine and plasma by postcolumn derivatization involving chemical oxidation followed by fluorescence reaction. AB - A high-performance liquid chromatographic method for the determination of catecholamines and their precursor and metabolites [amino compounds (norepinephrine, epinephrine, dopamine, normetanephrine, metanephrine, 3 methoxytyramine, and L-DOPA), acidic compounds (3,4-dihydroxyphenylacetic acid, vanillyl-mandelic acid, and homovanillic acid), and alcoholic compound [4-hydroxy 3-methoxyphenyl)ethylene glycol)] in human urine and plasma. Urine and plasma samples deproteinized with perchloric acid in the presence of isoproterenol and 3,4-dihydroxyphenylpropanoic acid (internal standards) are fractionated by solid phase extraction on a strong cation-exchange resin cartridge (Toyopak IC-SP S) into two fractions (amine fraction and acid-alcohol fraction). The compounds in each fraction are separated by an ion-pair reversed-phase chromatography on a TSK gel ODS-80TM with isocratic elution and on-line derivatized by periodate oxidation followed by a fluorescence reaction using meso-1,2 diphenylethylenediamine. The detection limits (S/N = 5) vary from 0.5 to 95 pmol/ml, depending on the compounds. PMID- 1632498 TI - Western blotting and immunochemical detection of histones electrophoretically resolved on acid-urea-triton- and sodium dodecyl sulfate-polyacrylamide gels. AB - We have developed a method for the efficient transfer of histones from acetic acid-urea-Triton X-100 (AUT)-polyacrylamide minislab gels to nitrocellulose. The AUT gel was equilibrated with 50 mM acetic acid and 0.5% sodium dodecyl sulfate and then with 62.5 mM Tris-HCl, pH 6.8, and 2.3% sodium dodecyl sulfate. An alkaline transfer buffer [25 mM 3-(cyclohexylamino)-1-propanesulfonic acid, pH 10, with 20% methanol] was used to electrophoretically transfer the strongly basic proteins from AUT or sodium dodecyl sulfate gels to nitrocellulose. The applicability of this approach in the immunochemical detection of ubiquitinated histone species is demonstrated. PMID- 1632499 TI - Ion-exchange high-performance liquid chromatography analysis of oligodeoxyribonucleotide phosphorothioates. AB - Oligodeoxynucleotide-containing phosphorothioate backbones have been used to regulate viral as well as cellular gene expression. The studies carried out in tissue culture have shown promising results on the use of oligonucleotide phosphorothioates as antiviral agents and, at present, study is underway to develop these oligonucleotide analogues as chemotherapeutic agents. To analyze and purify oligonucleotide analogues, high-performance liquid chromatography using weak anion exchange column has been described. The separation of oligonucleotide phosphorothioate is found to be length dependent. PMID- 1632500 TI - Beta-II conformation of all-beta proteins can be distinguished from unordered form by circular dichroism. AB - The CD spectrum of certain all-beta globular proteins resembles that of unfolded proteins with a characteristic negative band around 200 nm. The conformation of this class is tentatively termed beta-II, which had two features that were absent for unfolded proteins. First, beta-II proteins usually had CD bands due to aromatic side groups in the near-ultraviolet region. Second, the CD intensities both in the far- and in the near-uv region of these compact and rigid proteins usually showed a sharp transition upon thermal denaturation, whereas those of an unordered form changed linearly with rising temperature. PMID- 1632501 TI - Continuous spectrophotometric assays for beta-glucosidases acting on the plant glucosides L-picein and prunasin. AB - The neutral pH optimum beta-glucosidases of mammalian liver and almonds are each capable of hydrolyzing a number of plant glucosides, including L-picein (p hydroxyacetophenone-beta-D-glucoside) and prunasin (D-mandelonitrile-beta-D glucoside). Taking advantage of the marked differences in the spectra of the substrate/product pairs of L-picein/p-hydroxyacetophenone and prunasin/mandelonitrile, we have devised spectrophotometric assays that permit the continuous monitoring at pH 7.0 of p-hydroxyacetophenone (piceol) release from L-picein by guinea pig hepatic cytosolic beta-glucosidase and mandelonitrile from prunasin by almond beta-glucosidase. When L-picein hydrolysis was monitored at 320 nm and prunasin at 282 nm, the molar absorption coefficients determined for their products, namely piceol and mandelonitrile, were 3200 and 1360 M-1 cm 1, respectively. The kinetic parameter Km and Vmax values obtained using these spectrophotometric procedures for the guinea pig liver cytosolic beta-glucosidase acting on L-picein were 0.88 mM and 5.29 x 10(5) units/mg protein and for the almond beta-glucosidase acting on prunasin, Km 1.1 mM and Vmax 5.24 x 10(6) units/mg protein. These values agreed well with previously reported values obtained using less convenient, discontinuous assay procedures. PMID- 1632502 TI - Chromatography of proteins on columns of polyvinylpolypyrrolidone using adsorbed textile dyes as affinity ligands. AB - A simple and inexpensive chromatography system for proteins is introduced. When the amino derivatives of chlorotriazine dyes or other azo dyes were added to an aqueous slurry of the crosslinked polymer polyvinylpolypyrrolidone they were adsorbed, thus forming an immobilized dye chromatographic matrix. The association of the textile dyes with polyvinylpolypyrrolidone did not prevent them from acting as affinity ligands for proteins. Parameters such as ionic strength, dye concentration, and column size modulated the affinity effect exerted by the immobilized dyes. Lysozyme present in an egg white protein mixture bound to a column onto which the amino derivative of Procion Brown H-A was adsorbed and was eluted with a linear gradient of KCl. The resulting purification of the enzyme was 37-fold with 80% of the original activity being recovered. Free dye eluting with the lysozyme was removed on a column of polyvinylpolypyrrolidone equilibrated with 0.5 M KCl. After chromatography, the dye column was regenerated with 0.5 M NaOH and recharged with dye. The system presented here allows one to initially screen large numbers of potentially useful protein ligands to optimize a protein separation, followed by scaleup to a system size determined by the user. PMID- 1632503 TI - Large-scale cell separation by centrifugal elutriation. AB - Countercurrent elutriation is a powerful method for fast and gentle large-scale isolation of cells according to size and density. Current limitations of this approach are the suboptimal selectivity that is obtained and the fact that the total number of cells that can be separated per run is restricted. We describe a new separation chamber, which was calculated according to the hydrodynamic boundaries of the counterflow separation. In comparison to the chamber commonly in use, a fivefold higher cell number can be separated with this chamber at an increased separation selectivity. Furthermore the use of this chamber, which fits to the standard Beckman equipment, avoids large sampling volumes. PMID- 1632504 TI - Detection of acyl-coenzyme A thioester intermediates of fatty acid beta-oxidation as the N-acylglycines by negative-ion chemical ionization gas chromatography-mass spectrometry. AB - An analytical method for the separation and quantitation of acyl-CoA thioesters by gas chromatography-mass spectrometry is described. The method utilizes glycine aminolysis of the acyl-CoA thiolesters, esterification with pentafluorobenzyl bromide followed by gas chromatographic separation, and detection by negative chemical ionization mass spectrometry of the N-acylpentafluorobenzyl glycinates. The glycine aminolysis provides over 100-fold discrimination against oxygen esters and obviates the difficulty of removing trace contaminants of free fatty acids. The limit of detection of the described methodology for palmitoyl-CoA has been found to be 300 fmol, which improves at shorter chain lengths. Baseline separation was obtained for a standard mixture of seven acyl-CoAs (60 pmol injected) containing butyryl-CoA, hexanoyl-CoA, octanoyl-CoA, decanoyl-CoA, lauroyl-CoA, myristoyl-CoA, and palmitoyl-CoA. The above procedure is also applicable to the alpha-beta unsaturated and 3-hydroxyacyl-CoA derivatives, making it possible to quantify all of the intermediates in fatty acid oxidation, except the 3-ketoacyl-CoAs, in a single procedure. PMID- 1632505 TI - Evaluation of differential pulse polarography for the quantification of metallothionein--a comparison with RIA. AB - Two methods to quantify metallothionein (MT), differential pulse polarography (DPP) and radioimmunoassay (RIA), were compared for MT analysis of liver from Zn- and Cd-injected perch (Perca fluviatilis). Nine perch were intraperitoneally injected, twice a week during 2 weeks with ZnSO4 and CdCl2 to yield a total dose of 30 mg Zn and 3 mg Cd per kilogram body weight. Two samples, 100 and 200 mg from each liver, were homogenized separately and further prepared for DPP, RIA, and atomic absorption spectroscopy. MT values obtained by DPP were in good agreement with the MT values determined by RIA (r = 0.92). The relationship between the MT values analyzed with the two methods is described by the formula MTRIA = MTDPP x 0.99-0.048. Analysis of MT was not affected by sample size. MT values from individual liver samples plotted against the Cd and Zn content of the corresponding samples provided a high correlation. The correlation coefficient was 0.86 for MT values obtained by DPP and 0.92 for MT measured by RIA. It is concluded that DPP is a reliable method for analyzing MT in liver. PMID- 1632506 TI - A zymographic assay for detection of hyaluronidase activity on polyacrylamide gels and its application to enzymatic activity found in bacteria. AB - A zymographic assay for the determination of hyaluronidase activity in cell-free extracts on native polyacrylamide gels has been developed. In this assay an agarose replica of the polyacrylamide gel which contains hyaluronic acid and bovine serum albumin (BSA) was used. After an incubation at 37 degrees C to allow transfer and development of enzymatic activity, the hyaluronic acid and BSA were precipitated in the agarose gel with 2 M acetic acid. Areas of enzymatic activity appeared as clear zones in the agarose replica. The assay was sensitive and was used to demonstrate hyaluronidase activity in cell-free extracts from a number of bacterial and mammalian species. PMID- 1632507 TI - Analysis of macromolecular interactions using immobilized ligands. PMID- 1632508 TI - Preparative capillary electrophoresis based on adsorption of the solutes (proteins) onto a moving blotting membrane as they migrate out of the capillary. AB - A micropreparative capillary electrophoresis apparatus equipped with a new type of fraction collection device is described: solutes, such as proteins, are adsorbed onto a moving blotting membrane (for instance a polyvinylidene difluoride membrane) as they migrate electrophoretically out of the capillary. The adsorbed proteins are visualized by conventional protein staining methods or by fluorescent labeling. Specific identification of separated components by an immunological technique is demonstrated. The method also offers the potential to analyze proteins and peptides collected on the membrane by gas phase sequencing and mass spectrometry. PMID- 1632509 TI - Characterization of disulfide bond position in proteins and sequence analysis of cystine-bridged peptides by tandem mass spectrometry. AB - Tandem mass spectrometry employing high-energy, collisionally activated dissociation (CAD) is shown to be a useful method for sequencing through the cystine bridge of intermolecularly disulfide-bonded peptides. A characteristic triplet of intense fragment ions is observed corresponding to cleavage through and to either side of the disulfide bridge. These fragments define the masses of the linked peptides. Fragments due to peptide chain cleavage are also observed at lower abundance in the product-ion spectra and can be sufficient to sequence both of the disulfide-linked peptides without any prior knowledge of the peptide or protein sequence. Even in cases where the peptide sequence-related product-ion yields are poor, the intensities of the disulfide cleavage ions are usually sufficient to determine the molecular weights of the component cystine-bridged peptides. In this paper we demonstrate that the high-energy CAD tandem MS approach may be used to characterize disulfide-bonded peptides directly in complex enzymatic or chemical digests of native proteins. This obviates the need for individual purification of intermolecularly disulfide-linked peptides prior to analysis. The techniques are illustrated here for synthetic, inter- and intramolecularly disulfide-linked peptides and for human transforming growth factor-alpha (des-Val-Val-TGF-alpha), a compact protein containing 48 residues and three disulfides. PMID- 1632510 TI - Protein purification using a soluble affinity matrix: purification of estrogen receptor with estradiol-polylysine conjugate. AB - A new strategy for protein purification using a soluble affinity matrix is described. The method was used for purification of estrogen receptor. Cytosols from rat uteri and human fibroid uterine tissue, after fractionation by ammonium sulfate, were treated with estradiol-polylysine conjugate. The highly basic affinity complex was separated from other proteins by DEAE-Sephacel chromatography. After dissociation of the eluted complex with excess estradiol, the receptor was recovered by CM-Sephadex chromatography. A 2000-fold purification of the rat uterine estrogen receptor was obtained with an activity recovery of 35%. PMID- 1632511 TI - The precise radioimmunoassay of adenosine: minimization of sample collection artifacts and immunocrossreactivity. AB - Anti-adenosine antibodies were produced in rabbits immunized with N6 carboxymethyladenosine conjugated to methyl albumin. 125I-N6-Aminobenzyladenosine was synthesized and used as a high-specific-activity, high-affinity ligand. A radioimmunoassay (RIA) was developed that can detect 6.25 nM (312.5 fmol) of underivatized adenosine and cross-reacts less than 0.02% with adenine nucleotides and guanosine and not at all with 1 mM inosine. The sensitivity of the RIA can be increased to a detection limit of 0.125 nM (6.25 fmol) by derivitizing samples with benzyl bromide to form N6-benzyladenosine. The assay was adapted to an automated RIA procedure. Assay precision was increased by: (i) inhibiting slight adenosine deaminase activity present in anti-sera; (ii) treating buffers and albumin used in the RIA with charcoal to remove contaminating adenosine; and (iii) correcting for a small but variable component of immunoreactivity not attributable to adenosine. A second antibody prepared with a 2',3' disuccinyladenosine-albumin conjugate was also found to detect some non-adenosine mediated immunoreactivity in plasma samples. Immunointerference in human plasma was eliminated in samples treated with ZnSO4/Ba(OH)2 or partially purified over C18 Sep Paks to remove nucleotides and assayed after sample benzylation or succinylation. Human blood was mixed with a novel "stop" solution that was optimized to inhibit adenosine formation from AMP by greater than 99% and to inhibit adenosine uptake into red cells and degradation by greater than 94%. Human plasma/stop solution was assayed by RIA and HPLC with equivalent results. PMID- 1632512 TI - Internal protein sequence analysis: enzymatic digestion for less than 10 micrograms of protein bound to polyvinylidene difluoride or nitrocellulose membranes. AB - A procedure for the generation and isolation of internal peptide fragments for less than 10 micrograms of protein bound to either polyvinylidene difluoride (PVDF) or nitrocellulose membranes after electrophoretic transfer from sodium dodecyl sulfate-polyacrylamide gels (SDS-PAGE) is presented. This technique has produced internal sequence data for 120 peptides, with an average initial yield of 20 pmol. Membrane-bound proteins were enzymatically digested with either trypsin or endoproteinase Lys-C in the presence of 1% hydrogenated Triton X 100/10% acetonitrile/100 mM Tris-HCl, pH 8.0, for 24 h at 37 degrees C. The eluted peptides were then directly isolated by microbore HPLC for subsequent sequence analysis. One percent hydrogenated Triton X-100 did not inhibit enzymatic activity, distort HPLC resolution of peptides, or contain uv-absorbing contaminants that could interfere with peptide identification. Reproducible peptide maps and consistent recoveries are presented for standard proteins (3.5 8.0 micrograms) bound to either membrane, with higher recoveries for PVDF-bound proteins. Ninety percent of the proteins analyzed by this technique have produced results; representative peptide maps and sequence data are presented. This technique has a wide range of applications, particularly for proteins with blocked amino termini or those that can only be purified by SDS-PAGE or 2D isoelectric focusing SDS-PAGE. PMID- 1632513 TI - Determination of hydroxyproline by high pressure liquid chromatography. AB - A rapid, precise, and simple HPLC method provides an assay of hydroxyproline from tissue extracts or solutions of collagen. Samples are hydrolyzed with 6 N HCl, derivatized with phenyl isothiocyanate, and chromatographed on a small, C18 reverse-phase HPLC column. Hydroxyproline (Hyp) is separated from other amino acids and detected by absorption at 254 nm. The method detects 0.40 to 36 micrograms of Hyp with a linear response. Separation requires a total of 6 min, including column cleanup and reequilibration. All components are commercially available, making this a convenient method for routine measurement of collagen concentration. PMID- 1632514 TI - Polymerase chain reaction amplification of single-stranded DNA containing a base analog, 2-chloradenine. AB - By utilization of polymerase chain reaction techniques, single-stranded DNA of defined length and sequence containing a purine analog, 2-chloroadenine, in place of adenine was synthesized. This was accomplished by a combination of standard polymerase chain amplification reactions with Thermus aquaticus DNA polymerase in the presence of four normal deoxynucleoside triphosphates, M13 duplex DNA as template, and two primers to generate double-stranded DNA 118 bases in length. An asymmetric polymerase chain reaction, which produced an excess of single-stranded 98-base DNA, was then conducted with 2-chloro-2'-deoxy-adenosine 5'-triphosphate in place of dATP and with only one primer that annealed internal to the original two primers. Standard polymerase chain reaction techniques alone conducted in the presence of the analog as the fourth nucleotide did not produce duplex DNA that was modified within both strands. This asymmetric technique allows the incorporation of an altered nucleotide at specific sites into large quantities of single-stranded DNA without using chemical phosphoramidite synthesis procedures and circumvents the apparent inability of DNA polymerase to synthesize fully substituted double-stranded DNA during standard amplification reactions. The described method will permit the study of the effects of modified bases in template DNA on a variety of protein-DNA interactions and enzymes. PMID- 1632515 TI - The size dependence of cholate-dialyzed vesicles on phosphatidylcholine concentration. AB - The size dependence of vesicles prepared by dialysis of cholate from phosphatidylcholine (PC) dispersions has been investigated as a function of lipid concentration (at a constant applied lipid: detergent molar ratio of 0.7). Gel filtration of dialyzed samples produced a symmetrical profile shape, although quasielastic laser light scattering analysis of the fractions revealed an asymmetrical range of sizes about the peak for solutions containing elevated lipid concentrations. Vesicle diameters increased by approximately 20 nm for PC concentrations ranging from 10 to a maximum of 45 mg/ml. This was attributed to mixed micelle sizes being proportional to lipid concentration, since the diameters of vesicles produced from dialysis are determined by mixed micelle sizes. Before commencement of dialysis, mixed micelle sizes are proportional to lipid concentration and, although dialysis causes an increase in mixed micelle sizes, the phase ratios attained are larger for solutions containing elevated lipid concentrations. PMID- 1632516 TI - The use of three ferguson-plot-based calculation methods to determine the molecular mass of proteins as illustrated by molecular mass assessment of rat plasma carboxylesterases ES-1, ES-2, and ES-14. AB - The molecular masses of three rat-plasma carboxylesterases (ES-1, ES-2, and ES 14) were estimated by transverse-gradient polyacrylamide gel electrophoresis and subsequent application of Ferguson-plot-based calculation methods. Two electrophoretic buffer systems were used and the data subjected to either weighted or unweighted regression analysis. The Tris-boric acid buffer system produced significantly higher retardation coefficients than the Tris-glycine system. Molecular mass estimates were significantly higher with the Tris-glycine buffer system. Unweighted instead of weighted analysis produced significantly higher molecular mass estimates. Molecular mass estimates also depended on the calculation method, that is, the choice of calibration relationship with molecular size as a function of retardation coefficient. Three commonly used calibration relationships were compared. On the basis of their accuracy, both the weighted log[retardation coefficient] versus log[molecular mass] plot and the square root of retardation coefficient versus molecular radius were found suitable, provided that the Tris-boric acid buffer was used for electrophoresis. Using the former calibration relationship, the molecular masses of rat-plasma ES 1, ES-2, and ES-14 were 55.5, 61.1, and 65.3 kDa, respectively. PMID- 1632517 TI - Purification of brush border membrane vesicles from rat renal cortex by size exclusion chromatography. AB - Size-exclusion chromatography with controlled pore glass (CPG) was used in the further purification of renal brush border membrane vesicles (BBMV) isolated by the Ca precipitation method. The BBMV obtained had an almost spherical shape and their average diameter was about 95 nm in isotonic solution. The specific activities of alkaline phosphate and leucine aminopeptidase in the BBMV preparation were increased 18- and 17-fold, respectively, over those in the crude homogenate. The uptake of D-glucose by the purified BBMV in the presence of a sodium gradient reached 8.53 nmol/mg protein at 20 s. These results indicate that CPG chromatography is suitable procedure by which to obtain purified renal BBMV of homogenous size and with high specific marker enzyme activity for use in the study of membrane transport. PMID- 1632518 TI - Leaching of concanavalin A during affinity chromatographic isolation of cell surface glycoproteins from human fetal neurons and glial cells. AB - Preparation of surface glycoproteins from human fetal brain cells by affinity chromatography on Con A-Sepharose 4B was a problematic endeavor due to leaching of Con A from the matrix. Dissociation of Con A from the matrix took place irrespective of the presence of lipid and/or detergent and the buffer composition during chromatography and was apparently related to the nature of the protein under study. Pretreatment of Con A-Sepharose with 6 M guanidine or 8 M urea reduced Con A leaching. The Con A eluate also contained noncovalently associated glycolipid. Elution at 25 degrees C rendered fractions containing a higher degree of Con A and glycolipid contamination compared to the negligible contamination by these two components when elution was carried out at 4 degrees C. This phenomenon was attributed to the formation of heterogeneous mixed micelles of glycoprotein. PMID- 1632519 TI - Antibody from hen's eggs against a conserved sequence of the gametophytic self incompatibility proteins of plants. AB - A convenient way of producing effective antibodies to plant proteins is presented. It takes into account the following facts: (1) many plant proteins are highly glycosylated, thus giving rise to nonspecific antibodies which cross-react with other glycoproteins, (2) it is more common nowadays to know the DNA sequence of a protein coding gene than to have significant amounts of that protein well purified as antigen, and (3) eggs from immunized hens are very convenient sources of large amounts of antibodies. An antibody which specifically detects self incompatibility proteins (S-proteins) in Solanaceae was isolated. The published cDNA sequences and deduced amino acid sequences of Nicotiana alata (an ornamental tobacco) S-proteins were computer analyzed in order to recognize a peptide with a conserved sequence which would effectively give rise to antibodies. An adequate amount of this peptide was synthesized and part of it was coupled to a macromolecular carrier (bovine serum albumin). Antibodies to this peptide-carrier complex were recovered from egg yolks of immunized hen in amounts corresponding to 300 ml of antiserum per month. From the total immunoglobulin fraction isolated, the antibody specific for S-proteins was affinity purified over 100 fold on a peptide-coupled column. The antibody showed high levels of specificity for putative S-specific sequences in N. alata and in petunia. Also the size, polymorphy, and quantity of the detected antigens were in very good accordance with previously published data. In addition to the present application, this procedure should be useful for a wide variety of proteins. PMID- 1632520 TI - Electroluminescent lamp-based phase fluorometer and oxygen sensor. AB - We have tested 454-nm violet-emitting solid state electroluminescent lamps (ELLs) as inexpensive intensity-modulated excitation light sources for phase fluorometric oxygen sensors. Compared with blue-emitting silicon carbide LEDs, planar surface ELLs can be produced in various shapes and in large sizes. Accordingly, the overall optical output power emitted by ELLs is much higher than that of blue LEDs. By arranging a large-size ELL close to a large-size fluorescent chemical sensor, we obtained a large number of fluorescence photons allowing for the use of a pin photodiode instead of a photomultiplier tube as the detector. For a sinusoidal driving voltage at a frequency f, the ELL output light is modulated at 2f and at harmonics of 2f. Because of this nonlinear modulation characteristic, we used a square wave driving signal, resulting in a pulsed light output at a repetition rate twice the square wave frequency. The shortest light pulses obtained had a FWHM close to about 1 microsecond. This means that the violet ELLs used in our tests provide modulation frequencies at twice the square wave driving frequency and at all harmonics thereof up to about 1 MHz. This would allow the use of fluorescent chemical sensors with decay times as short as 30 ns, assuming that a phase shift of 10 degrees is adequate for the application. Due to the high ELL driving voltage, effective shielding is required to avoid electromagnetic interference between the modulated light source and the photodetector. Depending on the driving frequency and voltage applied, the ELLs showed a decrease in the optical output power to 50 or even 10% during the first 100 h of operation. PMID- 1632521 TI - Measurement of doxorubicin-induced lipid peroxidation under the conditions that determine cytotoxicity in cultured tumor cells. AB - We have investigated doxorubicin-induced lipid peroxidation by the measure of malondialdehyde (MDA) formation in rat glioblastoma cells and human breast carcinoma cells in culture. There was a significant production of MDA when the cells were incubated with pharmacologically relevant doxorubicin concentrations, i.e., concentrations that produce a significant cytotoxicity (0.1 micrograms/ml). At equitoxic doses, vincristine provided no lipid peroxidation, indicating that MDA formation is not a consequence of cell death. Doxorubicin-induced lipid peroxidation was maximal 24 h after incubation of the cells with doxorubicin, indicating that a delay was necessary for the free radical-mediated membrane damage induced by doxorubicin. In the presence of alpha-tocopherol in the culture medium, the doxorubicin-induced MDA formation was inhibited. The development of this method will help in defining the role of free radicals and lipid peroxidation in the cytotoxicity of doxorubicin. PMID- 1632522 TI - Genomic DNA microextraction: a method to screen numerous samples. AB - Many experimental designs require the analysis of genomic DNA from a large number of samples. Although the polymerase chain reaction (PCR) can be used, the Southern blot is preferred for many assays because of its inherent reliability. The rapid acceptance of PCR, despite a significant rate of false positive/negative results, is partly due to the disadvantages of the sample preparation process for Southern blot analysis. We have devised a rapid protocol to extract high-molecular-weight genomic DNA from a large number of samples. It involves the use of a single 96-well tissue culture dish to carry out all the steps of the sample preparation. This, coupled with the use of a multichannel pipette, facilitates the simultaneous analysis of multiple samples. The procedure may be automated since no centrifugation, mixing, or transferring of the samples is necessary. The method has been used to screen embryonic stem cell clones for the presence of targeted mutations at the Hox-2.6 locus and to obtain data from human blood. PMID- 1632523 TI - Carbohydrate composition analysis of bacterial polysaccharides: optimized acid hydrolysis conditions for HPAEC-PAD analysis. AB - The capsular polysaccharide from Haemophilus influenzae type b (polyribosyl ribitol-phosphate; PRP) and the capsular polysaccharides from Streptococcus pneumoniae types 6B, 14, 18C, and 23F (Pn6B, Pn14, Pn18C, and Pn23F) were subjected to acid hydrolysis using hydrofluoric (HF) and/or trifluoroacetic acid (TFA) and high-pH anion-exchange chromatography with pulsed amperometric detection in an effort to identify optimum hydrolysis conditions for composition analysis of their carbohydrate components. With the exception of PRP, composition analyses of polysaccharides containing a phosphate moiety in the repeating unit structure (Pn6B, Pn18C, and Pn23F) are significantly improved by subjecting the sample to HF hydrolysis (65 degrees C, 1 h) followed by TFA hydrolysis (98 degrees C, 16 h). This results in essentially quantitative hydrolysis of the phosphodiester bond to the carbohydrate components, which otherwise remained predominantly phosphorylated and poorly accounted for in the analysis. Optimum analysis of PRP was achieved following a 2-h hydrolysis with TFA at 80 degrees C, whereas Pn14 showed optimum results after a 16-h hydrolysis with TFA at 98 degrees C. These analyses also provide information about the relative susceptibility to acid hydrolysis of the various glycosidic and phosphodiester bonds in these polysaccharides, with evidence to suggest that the acid lability of a given bond can be dramatically different from one polysaccharide to another. PMID- 1632524 TI - Hydrophobic interaction chromatography fractionates lipoteichoic acid according to the size of the hydrophilic chain: a comparative study with anion-exchange and affinity chromatography for suitability in species analysis. AB - Hydrophobic interaction chromatography fractionated the lipoteichoic acid of Enterococcus faecalis into species of decreasing poly(glycerophosphate) chain length and decreasing extent of substitution with alpha-kojibiosyl residues (Glcp alpha 1----2Glcp alpha 1----). The chain length varied between 14 and 33 glycerophosphate residues per lipid anchor, the extent of glycosylation between 0.18 and 0.44 mol of alpha-kojibiosyl residues per mole of phosphorus, and, accordingly, the number of alpha-kojibiosyl substituents per chain between 3 and 15. Almost identical values were obtained when the same lipoteichoic acid was chromatographed on DEAE-Sephadex and concanavalin A, which separate molecular species according to increasing number of phosphate groups and alpha-kojibiosyl residues, respectively. Species from all three columns, which were identical in chain length and glycosylation, also had similar fatty acid patterns. These results prove the suitability of all three procedures for species analysis. One advantage of hydrophobic interaction chromatography over the other two procedures lies in its broader applicability since it is not dependent on negative charges or specifically binding oligosaccharide structures. Another advantage is the capacity of hydrophobic interaction chromatography to separate molecular species differing in the number of fatty acids [W. Fischer, H.U. Koch, and R. Haas (1983) Eur. J. Biochem. 133, 523-530] and render them accessible to molecular analyses. PMID- 1632525 TI - A particle beam-liquid chromatography-mass spectrometry method for the determination of lipoxygenase metabolites of arachidonic acid. AB - An application of the particle beam-liquid chromatography-mass spectrometry technique to the quantification of hydroxyeicosatetraenoic acids (15-, 12-, and 5 HETE) in biological samples is presented. The acids are extracted with Ethyl acetate and then transformed into pentafluorobenzyl esters, thus increasing the sensitivity of their detection by negative chemical ionization mass spectrometry. Reverse-phase HPLC separation of HETEs is performed in about 10 min with a water methanol gradient. The procedure shows a detection limit of nearly 0.5 pmol, about one order of magnitude lower than that of the widely used HPLC/UV methods. The quantitative determination is linear (r2 greater than 0.998) for all of the HETEs in the range tested (3-1500 pmol) and a CV lower than 8.5% was observed for repeated analysis of samples. As an application of the method, HETEs formed from endogenous arachidonate were evaluated in extracts obtained from coincubates of platelets and neutrophils stimulated with calcium ionophore A23187. PMID- 1632526 TI - Purification of human leucocyte DNA: proteinase K is not necessary. AB - A rapid nontoxic method for the purification of DNA from human leucocytes is described. Preliminary experiments which tested different methods of DNA purification indicated that digestion of proteins with proteinase K was unnecessary. This led to the development of a simple procedure involving lysis of the cells in SDS followed by extraction with 6 M NaCl. The method described overcomes the requirement for lengthy incubations in the presence of expensive proteinase K and subsequent extraction with toxic chemicals. PMID- 1632527 TI - A spectrophotometric microtiter-based assay for the detection of hydroperoxy derivatives of linoleic acid. AB - An assay for the detection of hydroperoxy derivatives of linoleic acid formed by the action of 15-lipoxygenase is described. The assay developed is based on a method first reported by Ohishi et al. (1985) Biochem. Int. 10, 205-211) with some important modifications. The assay described herein takes advantage of the ability of (9Z,11E)-13-hydroperoxyoctadecadienoic acid (13-HPODE), the product of the action of 15-lipoxygenase on linoleic acid, to oxidize N-benzoyl leucomethylene blue to methylene blue in the presence of hemoglobin. The resultant blue color is stable to light and air and can be quantified spectrophometrically at 660 nm. The linear range of the assay is 1.6-32 nmol (0.5 10 micrograms) of 13-HPODE. The utility of the assay can be extended to detect other peroxides as well as inhibitors of 15-lipoxygenase. The assay is a rapid, reliable method for the detection of lipid hydroperoxide production. PMID- 1632528 TI - Pressure support ventilation: technology transfer from the intensive care unit to the operating room. PMID- 1632529 TI - Convulsions associated with pediatric regional anesthesia. PMID- 1632530 TI - Pressure support ventilation decreases inspiratory work of breathing during general anesthesia and spontaneous ventilation. AB - Spontaneous ventilation may offer advantages over controlled mechanical ventilation (CMV), but increase in work of breathing may diminish its usefulness. During general anesthesia, respiratory depression and increased work of breathing often preclude spontaneous ventilation, and patients then receive CMV. We compared the inspiratory work of breathing of anesthetized patients who breathed with pressure support ventilation (PSV) with that associated with a demand gas flow and a standard anesthesia circle system. We studied nine consenting patients who underwent general inhaled anesthesia with or without regional supplementation. An anesthesia/ventilator system (Siemens 900D, Solna, Sweden) provided PSV (5 cm H2O) or demand gas flow during spontaneous inspiration. Gas flow during demand breathing and PSV was initiated when inspiration produced a 2 cm H2O reduction in airway pressure. An anesthesia machine (Drager Narkomed 3, Telford, Pa.) provided a gas flow rate of 6 L/min through a standard semiclosed circle system. Airway pressure, airway gas flow rate, and esophageal pressure were continuously transduced, and data or signals were conveyed to a computer. Tidal volume and respiratory rate were computed from the flow curve. The inspiratory work of breathing was calculated as the integral of the area subserved by a plot of esophageal pressure and tidal volume during inspiration. Heart rate and mean arterial blood pressure were recorded, and arterial blood was sampled for gas tension and pH analysis. No differences were found in pHa, Paco2, Pao2, tidal volume, respiratory rate, heart rate, or mean arterial blood pressure among the three modes of ventilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632531 TI - Long-term hypotensive technique with nicardipine and nitroprusside during isoflurane anesthesia for spinal surgery. AB - Short-term infusion of nicardipine can be used to induce deliberate hypotension but may result in plasma drug accumulation. To assess long-term nicardipine administration for deliberate hypotension in 10 patients in a moderately hemodiluted state who were undergoing spinal surgery, hemodynamics and plasma nicardipine concentrations were concomitantly measured before and 20, 80, and 140 min after starting nicardipine, at drug discontinuation, and 20 and 80 min later. A dose of 6.2 +/- 0.9 mg (mean +/- SEM) of nicardipine was initially required to obtain mean arterial blood pressures at 55-60 mm Hg. Maintenance doses of nicardipine were 3-5 mg/h. The duration of nicardipine administration was 270 +/- 20 min (mean +/- SEM). Hypotension was associated with decreased systemic and pulmonary vascular resistances, increased cardiac index, and decreased arteriovenous difference in O2 contents. Only two patients required homologous blood transfusion. Plasma nicardipine concentrations peaked at 110 +/- 21 ng/mL (mean +/- SEM) and then decreased to 38 +/- 11 ng/mL (mean +/- SEM) without changes in arterial blood pressure. After vasodilator discontinuation, hypotension was observed during a mean time of 43 min (range 27-88 min) despite plasma concentrations less than 20 ng/mL. No relationship was found between plasma nicardipine concentrations and hemodynamics. These findings suggest that an increasing effect of nicardipine over time may occur during prolonged administration. Because the reasons for this hysteresis remain unclear, use of nicardipine infusion during major surgery and anesthesia requires particular caution. PMID- 1632532 TI - Halothane and isoflurane inhibit endothelium-dependent relaxation elicited by acetylcholine. AB - The purpose of this study was to determine whether volatile anesthetics modify the release of endothelium-derived relaxing factor. We examined the effects of halothane and isoflurane on endothelium-dependent relaxation and 3',5'-cyclic guanosine monophosphate formation elicited by acetylcholine and ionophore A23187 in isolated rat aorta. Halothane and isoflurane (1%-2%) significantly attenuated acetylcholine-induced relaxation of the phenylephrine-contracted aorta but had no significant effect on relaxation induced by A23187, nitroprusside, and nitroglycerin. Basal and A23187 (10(-7) M)-stimulated levels of 3',5'-cyclic guanosine monophosphate were slightly lowered by halothane and isoflurane (2%). In contrast, the increase of 3',5'-cyclic guanosine monophosphate elicited by acetylcholine (10(-5) M) was significantly attenuated by halothane (2%) and abolished by isoflurane (2%). These findings indicate that halothane and isoflurane strongly inhibit the release of endothelium-derived relaxing factor elicited by acetylcholine. PMID- 1632533 TI - Effects on biliary tract pressure in humans of intravenous ketorolac tromethamine compared with morphine and placebo. AB - This study compared the effect of ketorolac tromethamine with that of morphine and placebo on biliary tract pressure. Intraoperatively, 31 anesthetized patients received either ketorolac (30 mg IV, n = 16) or morphine (5 mg IV, n = 15) after a cholecystectomy or gallstone removal. Intrabiliary tract pressure was measured 5 min after dosing. Postoperatively, 11 patients who had undergone biliary tract surgery received 10 mg of ketorolac or placebo, according to a randomized crossover design on 2 consecutive days. Intraoperatively, the biliary tract pressure did not change significantly from baseline after ketorolac administration. In the morphine group, there was significant increase in pressure over baseline. Postoperatively, there was no significant difference between ketorolac and placebo. We conclude that ketorolac has little or no effect on biliary tract dynamics; therefore, ketorolac may be a logical choice for analgesia in those situations in which spasm of the biliary tract is undesirable. PMID- 1632534 TI - Effects of ketorolac and bupivacaine on recovery after outpatient arthroscopy. AB - The effects of intraarticular bupivacaine, systemic ketorolac, and a combination of both treatments on postoperative pain and mobilization were evaluated in 60 healthy outpatients undergoing arthroscopic knee surgery under general anesthesia. After induction of anesthesia, patients received 2 mL of either ketorolac (60 mg) or saline solution (1 mL IV and 1 mL IM). On completion of surgery, the patient's knee joint was injected with 30 mL of either 0.5% bupivacaine or saline solution, according to a randomized, double-blind protocol. Only one patient (6%) receiving both medications complained of pain on awakening, compared with seven patients receiving either bupivacaine (37%) or ketorolac (41%) alone. Postoperative fentanyl was required by significantly fewer patients receiving combined therapy (n = 4, 21%) than either bupivacaine (n = 13, 62%) or ketorolac (n = 12, 60%) alone; however, there were no significant differences among the three treatment groups in terms of perioperative pain, nausea, or sedation visual analogue scale scores. Similarly, there were no differences in the times to ambulation or discharge or in analgesic requirements at home. In conclusion, a combination of systemic ketorolac and intraarticular bupivacaine decreased analgesic requirements and pain on awakening after arthroscopic surgery. However, the use of ketorolac alone or in combination with bupivacaine offered no advantage over bupivacaine alone with respect to recovery times after outpatient arthroscopy. PMID- 1632535 TI - Echocardiographic analysis of dysfunctional and normal myocardial segments before and immediately after coronary artery bypass graft surgery. AB - Echocardiography has revealed evidence of "subnormal" regional contraction patterns that result from myocardial ischemia and are often accompanied by nonadjacent "hyperkinetic" regions. Whether these regions of hyperkinetic wall motion persist unchanged or revert to normal after coronary artery bypass graft (CABG) surgery has not been studied in humans. Using echocardiography, we evaluated both dysfunctional and normal myocardial regions for changes in segmental wall motion and percent of systolic wall thickening that occurred immediately after CABG surgery in 32 patients. Segmental wall motion analysis before CABG surgery in these patients revealed that 170 (66%) of 256 myocardial segments were subnormal, of which 115 (67%) improved and 102 (60%) returned to normal immediately after CABG surgery. Eleven myocardial segments that were hyperkinetic before CABG surgery returned to normal after CABG surgery. Preoperatively, 162 (63%) of 256 myocardial segments had systolic wall thickening less than 30%, which increased from 11.8% +/- 8.9% to 24.3% +/- 14.3% (mean +/- SD) (P less than 0.01) postoperatively. Conversely, a reverse trend was found when systolic wall thickening was greater than 30% before CABG surgery: thickening decreased from 46.2% +/- 13.8% to 33.4% +/- 14.8% after CABG surgery (P less than 0.01). Thus, we conclude that immediately after CABG surgery, there is a recovery of function in some myocardial segments and a reduction in function in others. Furthermore, we conclude that the semiquantitative assessment of percent of systolic wall thickening is a more reliable (consistent) echocardiographic index of myocardial function compared with the qualitative assessment of segmental wall motion immediately after CABG surgery. PMID- 1632536 TI - Continuous endobronchial insufflation during internal mammary artery harvest. AB - Endobronchial insufflation of oxygen offers possible advantages over conventional ventilation modes in some clinical situations in which nonmovement of the chest may be desirable; however, endobronchial insufflation of oxygen has yet to be used during thoracic surgery in humans. Furthermore, the physiologic mechanisms underlying gas exchange during endobronchial insufflation of oxygen are unclear. This study assessed endobronchial insufflation of oxygen at 45 L/min in 11 patients with an open chest during internal mammary artery harvest. Cardiorespiratory function was measured at baseline during conventional mechanical ventilation and at 5-min intervals during the study period of 20-30 min. In all patients, clinically acceptable gas exchange was achieved, although PaCO2 increased from 32 +/- 3.2 to 44 +/- 7.5 mm Hg (mean +/- SD) at 5 min, but thereafter was unchanged (P greater than 0.1). Cardiac output, vascular pressures, and heart rate were unchanged, although pHa decreased. Surgical access for internal mammary artery harvesting was improved. No mucosal damage or complications occurred. During endobronchial insufflation of oxygen, efficacy of gas exchange and body weight were not correlated, but both subject height and age were correlated with high PaO2 and low PaCO2. We conclude that (a) endobronchial insufflation of oxygen can be used in patients with an open chest; (b) the efficacy of endobronchial insufflation of oxygen is probably improved by increased lung size and by collateral ventilation; and (c) cardiogenic gas mixing contributes little to gas exchange during endobronchial insufflation of oxygen. PMID- 1632537 TI - Modification of a new catheter for air retrieval and resuscitation from lethal venous air embolism: effect of nitrous oxide on air retrieval. AB - A modification of a new Arrow prototype catheter was evaluated for its ability to retrieve venous air emboli and for its effect on the success rate of resuscitation from venous air emboli in dogs anesthetized with isoflurane and nitrous oxide (66%) in oxygen. In an additional group of dogs, nitrogen was substituted for nitrous oxide in the inspired gases to determine whether the presence of nitrous oxide (as traditionally used in this model of lethal venous air emboli) increased the apparent amount of gas retrieval or altered the success rate of resuscitation. Dogs were placed in the seated position with the head 90 degrees to the horizontal. The modified Arrow prototype catheter was placed with the proximal orifice just above the superior vena cava-right atrial junction and the distal orifice near the mid-right atrium. Dogs were then given a predetermined lethal dose of air (5 mL/kg) over 30 s through the jugular vein. Attempts to aspirate venous air emboli were begun with the first decrease in expired CO2. The amounts of gas retrieved, expressed as a percent of the injected air, and the incidence of successful resuscitation were compared between groups. In both treatment groups (nitrous oxide and nitrogen), the percent of injected venous air retrieved (73% +/- 13% and 65% +/- 21%, mean value +/- SD, respectively) and success rate of resuscitation (four of six dogs in each group) were significantly increased compared with the control group in which no attempt was made to retrieve injected venous air, and none of the six dogs survived.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632538 TI - Methylprednisolone does not decrease eicosanoid concentrations or edema in brain tissue or improve neurologic outcome after head trauma in rats. AB - Methylprednisolone was recently reported to significantly improve motor and sensory function after acute spinal cord injury in patients. Our study was designed to determine whether methylprednisolone exerts a beneficial effect after head injury. Diethyl ether-anesthetized rats were assigned to receive surgery with no cranial impact and no methylprednisolone (group A, n = 13); surgery with no cranial impact and intraperitoneal methylprednisolone (greater than or equal to 60 mg/kg) (group B, n = 8); surgery with cranial impact and no methylprednisolone (group C, n = 8, and group E, n = 8); or surgery with cranial impact and methylprednisolone (greater than or equal to 60 mg/kg) (group D, n = 15, and group F, n = 13). Neurologic severity score was determined at 1, 2, 4, and 24 h (when appropriate) after injury, and brain tissue eicosanoid levels and cerebral edema were determined when the animals were killed (4 h after injury in groups C and D and 24 h after injury in groups E and F). Treatment with methylprednisolone did not improve neurologic severity score or edema formation and did not alter brain tissue levels of prostaglandin E2, thromboxane B2, or 6 keto-prostaglandin F1 alpha at any time period. The authors conclude that methylprednisolone does not exert a beneficial effect on brain tissue edema or functional activity after cranial impact in rats. PMID- 1632539 TI - Alfentanil-induced rigidity in newborn infants. AB - The authors evaluated whether alfentanil could be given before treatment procedures in critically ill mechanically ventilated neonates without adverse effects. Alfentanil (mean dose 11.7 micrograms/kg, range 9-15) was given intravenously to 20 mechanically ventilated critically ill newborn infants (mean birth weight 2510 g, range 1490-3990) during the first 3 days of life before treatment procedures. Heart rate, arterial blood pressure, transcutaneous partial pressure of O2, respiratory rate, and general activity were observed continuously from 10 min before the administration of alfentanil until 1 h after it. Plasma alfentanil concentrations were measured in 15 subjects. The pharmacokinetics of alfentanil varied greatly among the subjects. The hemodynamic changes were not clinically significant, and the most important side effect was muscle rigidity. Nine infants had mild or moderate rigidity, which had little or no effect on ventilation. Four infants had severe rigidity and jerking comparable to convulsive activity, transiently impairing ventilation and oxygenation for approximately 5-10 min. Increased inspired oxygen and increased pressure by manual ventilation were needed to prevent hypoxemia. Electroencephalographic recordings for three infants during alfentanil administration showed no evidence of increased seizure activity. We conclude that alfentanil should not be used for newborn infants without simultaneous muscle relaxation because of the danger of rigidity. PMID- 1632540 TI - Preoperative screening for pediatric ambulatory surgery: evaluation of a telephone questionnaire method. AB - The purpose of this study was to determine whether preoperative screening of pediatric patients, accomplished by means of a preoperative telephone call to their parents, would decrease the rate of cancellation or postponement of ambulatory surgical procedures. Data from 5031 patients scheduled for ambulatory surgery were collected. During phase I of the study, when phone calls were attempted only during business hours, we contacted 805 of 1662 (48%) of patients' parents. The contact rate improved to 71% (2403 of 3369 patients) during phase II of the study, when phone calls were made in the evening, and parents were encouraged by the surgeons to call the ambulatory unit. Approximately 13% of the contacted parents reported a history of medical problems in their children. A preoperative anesthesia consultation was required in 2.8% of the patients whose parents were contacted. The rate of postponed or canceled surgery among those who could not be screened was 14.8%; among patients who were screened, it was 9.7% (P less than 0.001). Patients in the former group were more likely than those in the latter group to require inpatient care for monitoring or treatment of underlying medical problems (1.3% vs 0.3%, respectively; P less than 0.05). We conclude that a preoperative telephone interview is an effective method for screening pediatric ambulatory surgical patients. PMID- 1632541 TI - Continuous low-dose 3-in-1 nerve blockade for postoperative pain relief after total knee replacement. AB - We have investigated the value of a 3-in-1 nerve block, followed by a continuous low-dose infusion of bupivacaine into the femoral nerve sheath for postoperative analgesia after total knee replacement. Thirty-seven patients were randomly allocated to either a control group or a study group. The study group had a catheter placed in the ipsilateral femoral nerve sheath. A 3-in-1 nerve block was then performed in the study group with injection of 30 mL of 0.25% bupivacaine through the catheter. This was followed by a continuous infusion of 0.125% bupivacaine at 6 mL/h. The study group had significantly lower pain scores 4 and 24 h postoperatively (P less than 0.01) and required less postoperative opioid analgesic medication (P less than 0.01) than the control group. The authors conclude that a continuous low-dose infusion into the femoral nerve sheath results in better pain relief than conventional intramuscularly administered narcotics after total knee arthroplasty. PMID- 1632542 TI - Continuous interpleural infusion of bupivacaine for postoperative analgesia after surgery with flank incisions: a double-blind comparison of 0.25% and 0.5% solutions. AB - Postoperative analgesia, as assessed by visual analogue scale scores (0-10) and patient-controlled analgesia morphine requirements, pulmonary function (forced vital capacity and forced expiratory volume in 1 s), and plasma bupivacaine concentrations were studied in patients receiving interpleural blockade with bupivacaine after surgery with a flank incision. Two groups of 10 patients received either 0.5% or 0.25% bupivacaine, both with epinephrine (5 micrograms/mL). Pain relief was initiated when patients had visual analogue scale scores greater than or equal to 4. Patients received 21 mL of bupivacaine 0.25% or 0.5% in a double-blind fashion. One hour later, a continuous infusion of 5 mL/h of the study solution was started. At the same time, patient-controlled analgesia became accessible to the patients. The onset time of pain relief and the area under the visual analogue scale score-time curves over the first 8 h were similar in both groups. Patient-controlled analgesia morphine use was also similar in the 0.25% (21.3 +/- 14.6 mg) and 0.5% (21.0 +/- 16.0 mg) groups (mean +/- SD). In both groups, forced vital capacity and forced expiratory volume in 1 s improved significantly within 60 min (P less than 0.05). Peak plasma concentrations (Cmax) and the area under the plasma concentration-time curve (AUC) over 24 h were higher (P less than 0.001) in the 0.5% group (Cmax, 1.47 +/- 0.37 micrograms/mL; AUC, 1511 +/- 323 micrograms.mL-1.min) than those in the 0.25% group (Cmax, 0.55 +/- 0.22 micrograms/mL; AUC, 680 +/- 118 micrograms.mL 1.min) (mean +/- SD).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632543 TI - Compartment syndromes: concepts and perspectives for the anesthesiologist. PMID- 1632545 TI - Succinylcholine-induced hyperkalemic arrest in a patient with severe metabolic acidosis and exsanguinating hemorrhage. PMID- 1632544 TI - Seizures occurring in pediatric patients receiving continuous infusion of bupivacaine. PMID- 1632546 TI - Succinylcholine-induced hyperkalemia 8 weeks after a brief paraplegic episode. PMID- 1632547 TI - Vertebral artery pseudoaneurysm: a rare complication of internal jugular vein catheterization. PMID- 1632548 TI - Craniotomy in a patient with Eisenmenger's syndrome. PMID- 1632549 TI - A "new" needle? PMID- 1632550 TI - A simple method of MDI administration in the intubated patient. PMID- 1632552 TI - Labeling of syringes to prevent "drug swaps". PMID- 1632551 TI - Use of a Wilson Convex Frame in removing "irretrievable" epidural catheters. PMID- 1632553 TI - A simple device to demonstrate the law of Laplace. PMID- 1632554 TI - The 3.5/4.5 modification for fiberscope-guided tracheal intubation using the laryngeal mask airway. PMID- 1632556 TI - When is a fact, in fact, a fact? PMID- 1632555 TI - Effect of propofol in brainstem auditory evoked responses. PMID- 1632557 TI - Plug it in! PMID- 1632558 TI - What caused the unilateral epidurogram and bilateral epidural analgesia? PMID- 1632560 TI - Contralateral anesthesia following interscalene block. PMID- 1632559 TI - Reinserting a catheter into a single-use adapter: an unsafe method. PMID- 1632561 TI - Ventilatory depression and midazolam. PMID- 1632562 TI - Anesthetic management in Charcot-Marie-Tooth disease. PMID- 1632563 TI - Interpleural regional analgesia--a simple cause of catheter obstruction. PMID- 1632564 TI - Effect of cardiac dysfunction upon diastolic cerebral blood flow. AB - The transcranial Doppler (TCD) studies performed in 54 patients with various forms of cardiac dysfunction were reviewed and the results compared with those of normal individuals. There were 4 patients with aortic insufficiency, 5 being treated by intra-aortic balloon pumps, 12 patients with atrial fibrillation, 11 with syncope, and 22 undergoing cardiopulmonary resuscitation. In all instances, significantly low or even absent diastolic cerebral perfusion was found. The importance of this parameter, in the future evaluation and management of similar patients, is discussed. PMID- 1632565 TI - Electrocardiographic prediction of the success of coronary reperfusion by intravenous thrombolytic therapy: an experimental study. AB - The accuracy of electrocardiograms (ECGs) in predicting the success of coronary reperfusion by intravenous (IV) thrombolytic therapy was studied in 49 canine acute myocardial infarctions (MI), induced by occlusive thrombus in the left anterior descending (LAD) coronary artery. Two hours after the onset of MI, urokinase (UK, 3 x 10(4) U/kg) was administered IV and the heart was observed for one further hour. LAD flow and epicardial ECGs were recorded continuously. LAD flow was restored by UK in 26 of 49 animals (Group I); restored LAD flow was stable in 17 of the 26 (Group IA) and unstable with repeated fluctuations in the other 9 (Group IB) during the follow-up period. No coronary reflow was obtained by thrombolysis in 23 of 49 animals (Group II). The best electrocardiographic criterion for predicting coronary reperfusion was reduction of ST elevation by more than 25%, which had a predictive accuracy of 86%. There was a significant correlation between the grade of improvement of coronary blood flow and reduction of ST elevation in Group IA (p less than 0.01), but not in Group IB, indicating that unstable coronary blood flow following thrombolysis due to residual thrombus appears to be one of the major factors preventing accurate prediction of coronary reperfusion with thrombolysis on the basis of changes in ST elevation. PMID- 1632566 TI - Clinical and angiographic features of patients from the Indian subcontinent treated with intravenous streptokinase for acute myocardial infarction: experience in Qatar. AB - The authors reviewed their experience with 245 patients who were treated with intravenous streptokinase for acute myocardial infarction at an average time of less than three hours from the onset of chest pain. Of these, 148 patients were from the Indian subcontinent (Group 1) and the remaining (Group 2) were predominantly from an Arabic background. Group 1 patients were younger and had lower serum cholesterol and fibrinogen levels than the Group 2 patients. Group 1 patients had a lower incidence of previous myocardial infarction (p = 0.0006) and antecedent angina pectoris (p = 0.017). A patency rate of 77.5% was seen in all patients studied at 5.37 +/- 2.96 days after admission and was similar in both the groups. Group 1 patients had a lesser extent of coronary artery disease (p = 0.01) manifested as a higher incidence of single-vessel disease (p = 0.06) and a lower incidence (p = 0.06) of three-vessel obstruction. The overall mortality for the initial hospitalization was 2.18% and showed no difference between the two groups. Patients from the Indian subcontinent presenting with acute myocardial infarction appear to be a unique population in that they are younger, have a somewhat lower cardiac risk profile, and have less extensive coronary artery disease than their Arabic counterparts. PMID- 1632567 TI - Differential exercise effects of captopril and nadolol in patients with essential hypertension. AB - In a crossover study, 12 patients with mild to moderate hypertension were given placebo, captopril (12.5 to 50 mg three times a day), and nadolol (20 to 160 mg once a day) to control the resting diastolic blood pressure to a nearly identical degree (p less than 0.0001) (106.1 +/- 4 placebo, 89.6 +/- 8 captopril, 89.8 +/- 7 nadolol). Both drugs lowered (p less than 0.0004) systolic and diastolic blood pressure at rest and during exercise. However, systolic blood pressure lowering during exercise was more pronounced (p less than 0.05) with nadolol than with captopril (difference of 6 mmHg, 16 mmHg, and 21 mmHg at 5.0, 7.0, and 9.0 metabolic equivalents (METS) respectively). Heart rate was lower (p less than 0.05) at rest and during exercise with nadolol as compared with placebo and with captopril. These data imply different mechanisms of action of the two drugs at rest and during exercise and may help in selection of drug therapy in special patient subsets. PMID- 1632568 TI - Coronary angioplasty in patients with previous coronary artery bypass grafting. AB - Between 1982 and 1990, in 134 patients with prior coronary artery bypass grafting and recurrent angina, repeat coronary angiography and balloon angioplasty of stenoses in grafts or native arteries were attempted. Mean age of grafts was 45.6 months, range three days to twelve years. At the time of angioplasty, 6 patients had one-vessel-disease, 33 had two-vessel-disease, and 95 had three-vessel disease. A total of 182 lesions were dilated: 55 venous grafts, 3 internal mammary artery grafts, and 124 native vessels. Forty-nine of 55 (89%) venous grafts could be successfully dilated, and in 3 internal mammary artery grafts, a stenosis reduction greater than 50% was achieved. In 65 of 88 (74%) grafted native arteries, dilation success was achieved. Twenty-seven of 36 (75%) patients with prior bypass surgery to other arteries had successful angioplasty of nongrafted native arteries. Three patients underwent emergency bypass surgery after dissection and acute occlusion: one of them died in cardiogenic shock secondary to acute myocardial infarction. The angiographic success rate in grafts was slightly higher than in native arteries (90% vs 74%). These data indicate that percutaneous transluminal coronary angioplasty in patients after bypass surgery is possible at a low risk (3%) and constitutes an effective therapy in symptomatic patients. PMID- 1632569 TI - Comparison of three progressive exercise protocols in peripheral vascular occlusive disease. AB - Although claudication pain and hemodynamic responses to exercise are usually clinically assessed via graded treadmill walking, measuring these responses to other commonly performed tasks may yield a more nearly complete evaluation of peripheral vascular occlusive disease. Thus, the purpose of this study was twofold: (1) to determine the reliability of claudication and hemodynamic responses to level walking and stairclimbing and (2) to compare these responses with those obtained with graded walking at similar oxygen consumption. Ten patients with stable claudication symptoms performed graded walking, level walking, and stairclimbing progressive protocols with respective increases in grade, walking speed, and stepping rate on a modified stairclimbing device every two minutes. Similar peak oxygen consumption (13.60 to 14.18 mL/kg/min) was attained with the three protocols (P = NS). Reliability coefficients for the times to onset and to maximal claudication pain during level walking (R = 0.95 and 0.95, respectively) and during stairclimbing (R = 0.92 and 0.82, respectively) were similar to those previously obtained during graded walking. Reliability coefficients for foot transcutaneous oxygen tension during and following level walking (R = 0.78 to 0.96) and stairclimbing (R = 0.65 to 0.98) and for ankle systolic blood pressure following level walking (R = 0.95 to 0.97) and stairclimbing (R = 0.90 to 0.98) were also similar to those previously found with graded walking. Additionally, claudication and hemodynamic measurements were similar among the three exercise protocols. Thus, because graded walking, level walking, and stairclimbing progressive exercise protocols yield reliable and similar information about the hemodynamic severity of peripheral vascular occlusive disease, only one is needed for evaluation. PMID- 1632570 TI - Spontaneous idiopathic subclavian arteriovenous fistula: a case report. AB - Systemic arteriovenous (AV) fistulas are a rare but correctable cause of hyperkinetic circulation and congestive heart failure. They are generally due to catheterization procedures, surgery, trauma, or aneurysms. A case of truly spontaneous AV fistula between left subclavian artery and left innominate vein is described. This patient presented with symptoms that might clinically be mistaken for a carpal tunnel syndrome. The discovery of a continuous to-and-fro murmur on her left upper sternal border led to the correct diagnosis. Surgical ligature of the fistula provided complete relief of the woman's symptoms. PMID- 1632571 TI - Cerebral microcirculatory changes after cerebral embolization induced by glass bead injection in rabbits. AB - The authors investigated microcirculatory changes in cerebral embolization induced by an injection of glass beads (mesh size 20/400, 15 mg/body) using intravital microscopy and reflectance spectrophotometry in normal rabbits. Cerebral embolization with the glass bead injection reduced the inner diameter of cerebral arterioles, the index of cerebral hemoglobin concentration (IHb), and the index of oxygen saturation (ISO2). Moreover, platelet aggregation rates and plasma levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto PGF1 alpha) appreciably increased. During observation of the pial vasculature, "white bodies" became visible at the entrance of arteriolar branchings two to three minutes after the glass bead injection. After indomethacin administration (3 mg/kg, IV), they could not observe white bodies, and platelet aggregation rates were significantly reduced. The plasma levels of TXB2 and 6-keto-PGF1 alpha were also significantly reduced. These findings suggest that glass beads do injury to the microvascular endothelial cells leading to development of white bodies, ie, "flying thrombi." Therefore, the cerebral microvascular embolization induced by the glass bead injection appears to be an experimental model for evaluating efficacy of remedies for the cerebral microcirculatory disorders. PMID- 1632572 TI - Diagnosis of atrial septal aneurysm by two-dimensional echocardiography--a case report. AB - A patient who was evaluated for a syncopal episode was found by two-dimensional (2D) echocardiography to have an aneurysm of the atrial septum. The atrial septal aneurysm appeared as a localized outpouching of the atrial septum that protruded into the left atrium during systole and into the right atrium during early diastole. The 2D echocardiography permits the definitive diagnosis of this condition by a noninvasive technique. PMID- 1632573 TI - Right-sided cardiac thromboembolism and its successful treatment with streptokinase: case report. AB - A sixty-eight-year-old woman with a clinical diagnosis of pulmonary embolism and large right-heart embolus on echocardiography is presented. Because of the critical clinical condition of the patient and the inability to perform surgical intervention, thrombolytic treatment (streptokinase) was administered. The patient's condition improved, the right-heart embolus disappeared, and on the perfusion lung scan there was only one small perfusion defect in the right lung. The authors consider thrombolysis to be appropriate treatment for right-heart thromboembolism whenever surgical embolectomy is not possible. PMID- 1632574 TI - Holt-Oram syndrome in an elderly patient--a case history. AB - The authors present a typical case of Holt-Oram syndrome in an eighty-year-old woman. The patient had atrial-septal defect and phocomelia but was independent in the activities of daily living. PMID- 1632575 TI - Cellular actions of opiates and cocaine. PMID- 1632576 TI - Cortico-subcortical interactions in behavioral sensitization: differential effects of daily nicotine and morphine. PMID- 1632577 TI - Cellular mechanisms of behavioral sensitization to drugs of abuse. PMID- 1632578 TI - Mesocorticolimbic dopamine systems: cross-sensitization between stress and cocaine. PMID- 1632579 TI - Effects of chronic ethanol and benzodiazepine treatment and withdrawal on corticotropin-releasing factor neural systems. PMID- 1632580 TI - Alterations in biodistribution of 11C-methamphetamine (MAP), 14C-MAP, and 123I-N isopropyl-iodoamphetamine (IMP) in MAP- and cocaine-sensitized animals. AB - Alterations in brain distribution of 11C-MAP, 14C-MAP, and 123I-IMP in MAP- and cocaine-sensitized animals were examined to investigate the mechanism involved in increased dopaminergic transmission and behavioral sensitization. First, a significant increase in 11C-MAP radioactivity in the striatum and hypothalamus was found in the mice pretreated with MAP for 7 days. Secondly, in MAP-sensitized rats, marked increases in 14C-MAP radioactivity were found in the striatum and limbic forebrain, respectively (370% and 650%). These findings may propose a new hypothesis that subchronic MAP administration may result in a long-term change in the presynaptic cell membrane at the nerve terminal which may in turn cause an increase in both MAP and DA uptake accompanied by an increased release of DA at the synaptic cleft. PMID- 1632581 TI - A lasting vulnerability to psychosis in patients with previous methamphetamine psychosis. AB - Chronic MAP abuse may produce a lasting vulnerability of the brain which leads to a paranoid delusional psychosis with hallucinations similar to schizophrenia. This view is based on the clinical observations that duration of the psychotic episodes could last quite long after excretion of MAP in the urine, and that reuse of MAP, alcohol ingestion and nonspecific psychological stressors lead to acute recurrence of psychotic episodes whose clinical features are almost identical to the initial episode in patients with prior MAP psychosis. The experimental studies indicate that a lasting change at the nerve terminal membranes, namely transporters of MAP and dopamine at the uptake sites, in the striatum and nucleus accumbens may be a cause for induction and expression of stimulant-induced sensitization, which may relate to vulnerability to schizophrenia-like psychotic episodes in MAP psychosis. PMID- 1632582 TI - Neural mechanisms of drug reinforcement. AB - The brain substrates involved in the effect of cocaine on brain stimulation reward, in the psychomotor activation associated with cocaine, and in cocaine self-administration appear to be focused on the medial forebrain bundle and its connections with the basal forebrain, notably the nucleus accumbens. Chronic access to cocaine produces a withdrawal state as reflected in increases in brain stimulation reward thresholds, and this change in reward threshold appears to be opposite to the actions of the drug administered acutely. These effects are thought to reflect a change in the activity of reward elements in the medial forebrain bundle and may be responsible for the negative reinforcing state associated with the anhedonia of cocaine withdrawal. Opiate receptors particularly sensitive to the reinforcing effects of heroin also appear to be located in the region of the nucleus accumbens and the ventral tegmental area. There is good evidence for both dopamine-dependent and dopamine-independent opioid interactions in the ventral tegmental-nucleus accumbens connection. In addition, the opiate receptors in the region of the nucleus accumbens may become sensitized during the course of opiate withdrawal and thus become responsible for the aversive stimulus effects of opiate dependence. Reliable measures of the acute reinforcing effects of ethanol have been established in rat models, and substantial evidence exists to show that non-deprived rats will orally self administer pharmacologically relevant amounts of ethanol in lever-press choice situations. Neuropharmacological studies of ethanol reinforcement in non dependent rats suggest important roles for serotonin, GABA and dopamine. A role for opioid peptides in ethanol reinforcement may reflect more general actions of opioid peptides in consummatory behavior. Studies of ethanol dependence have implicated brain GABAergic and CRF systems in the more motivational aspects of withdrawal. Future studies will need to focus on the common neurobiologic changes associated with all these drugs, particularly regarding their hedonic and motivational properties. PMID- 1632583 TI - Self-stimulation and drug reward mechanisms. PMID- 1632584 TI - Drug motivation and abuse: a neurobiological perspective. PMID- 1632585 TI - Neurochemical correlates of cocaine and ethanol self-administration. PMID- 1632586 TI - Cortical regulation of self-administration. PMID- 1632587 TI - High potency cocaine analogs: neurochemical, imaging, and behavioral studies. PMID- 1632588 TI - Methamphetamine-induced neurotoxicity: structure activity relationships. PMID- 1632589 TI - Genetic determinants of ethanol reinforcement. AB - In this paper, we present examples of some of the several behaviors which have been taken to indicate the reinforcing efficacy of drugs, including ethanol. Efforts to identify the genetic determinants of these behaviors have employed diverse pharmacogenetic methods. For example, we have used selective breeding to develop mice selected for severe or attenuated ethanol withdrawal and have found that Withdrawal Seizure Prone mice show a greater conditioned preference for ethanol-associated locations than the selected Withdrawal Seizure Resistant line. Similarly, HOT mice, selected for insensitivity to ethanol-induced hypothermia, had greater conditioned place preference after ethanol training than COLD mice, selected for ethanol hypothermic sensitivity. We have also developed selected mouse lines responsive or unresponsive to ethanol-stimulated locomotor activity. These FAST and SLOW lines develop sensitization rather than tolerance to ethanol induced activity. Using inbred strains of mice, others had shown that strains differed in preference for drinking ethanol solutions. We found that these strains also differed in acceptance of ethanol. Single-gene techniques have been used to show that preference drinking is significantly altered in mutant rodent strains lacking hypothalamic vasopressin, or with nephrogenic diabetes insipidus. In a specific panel of Recombinant Inbred mouse strains, we found that a single gene appeared to control a significant portion of the variance in preference drinking. These examples show that traits putatively related to drug reinforcement show substantial genetic control. Specifically, single-gene methods show promise of identification and mapping of genes related to drug reinforcement. PMID- 1632590 TI - Chromosome mapping of gene loci affecting morphine and amphetamine responses in BXD recombinant inbred mice. PMID- 1632591 TI - Behavioral and pharmacological determinants of drug abuse. PMID- 1632592 TI - Conditioned sensitization to the psychomotor stimulant cocaine. PMID- 1632593 TI - Classical conditioning in drug-dependent humans. AB - Repetitive use of psychoactive drugs produces a variety of learned behaviors. These can be classified in the laboratory according to an operant/classical paradigm, but in vivo the two types of learning overlap. The classically conditioned responses produced by drugs are complex and bi-directional. There has been progress in classifying and predicting the types of conditioned responses, but little is known of mechanisms. New techniques for understanding brain function such as micro-dialysis probes in animals and advanced imaging techniques (PET and SPECT) in human subjects may be utilized in conditioning paradigms to "open the black box." Because the existence of conditioned responses in drug users is now well established, clinical studies have been instituted to determine whether modification of conditioned responses can influence clinical outcome. A recently completed study in cocaine addicts has produced evidence that outcome can be improved by a passive extinction technique over an 8-week outpatient treatment program. PMID- 1632594 TI - Cocaine-induced changes in extracellular levels of striatal dopamine measured concurrently by microdialysis with HPLC-EC and chronoamperometry. PMID- 1632595 TI - Behavioral temperature regulation during withdrawal from ethanol dependency in mice. PMID- 1632596 TI - Methamphetamine-induced conditioned place preference or aversion depending on dose and presence of drug. PMID- 1632597 TI - Cocaine and other local anesthetics block hippocampal long-term potentiation. PMID- 1632598 TI - Effect of a benzodiazepine derivate Ro 15-4513 on ethanol-free selection and CNS mitochondrial energetics in rats. AB - 1) Females are higher EtOH drinkers than males in E.F.S. experiments in rats. 2) Ro 15-4513 inhibited intake of EtOH. 3) Hypothalamus mitochondrial energetics, studied at Sites I and II, showed Ro 15-4513 inhibition of these parameters at different doses by sex: effects were seen in females at 15 mg and in males at 10 mg/kg rat/24 h. An uncoupled effect between electron transport and ADP/O was found. PMID- 1632599 TI - Sensitization and individual differences to IP amphetamine, cocaine, or caffeine following repeated intra-cranial amphetamine infusions. PMID- 1632600 TI - Solubilization of the cannabinoid receptor from rat brain membranes. PMID- 1632601 TI - Different pharmacodynamics for diazepam and flunitrazepam? PMID- 1632602 TI - Psychomotor stimulant effect of cocaine is affected by genetic makeup and experimental history. PMID- 1632603 TI - Nifedipine blocks the development of tolerance to the anticonvulsant effects of ethanol. PMID- 1632604 TI - Influence of chronic cocaine on monoamine neurotransmitters in human brain and animal model: preliminary observations. PMID- 1632605 TI - Repeated injection of cocaine potentiates methamphetamine-induced toxicity to dopamine-containing neurons in rat striatum. PMID- 1632606 TI - Opioid modulation of alcohol intake in monkeys by low doses of naltrexone and morphine. PMID- 1632607 TI - Seizure incidence enhancement with increasing alcohol intake. PMID- 1632608 TI - Studies of the mechanism of inhibition of the dopamine uptake carrier by cocaine in vitro using rotating disk electrode voltammetry. PMID- 1632609 TI - Evidence for a possible role of the 5-HT2 antagonist ritanserin in drug abuse. PMID- 1632610 TI - Prenatal neurochemistry of cocaine. PMID- 1632611 TI - Ingested ethanol as a factor in double vision. PMID- 1632612 TI - Effect of haloperidol on craving and impaired control following alcohol consumption in alcoholic subjects. PMID- 1632613 TI - Locomotor responses of FAST and SLOW mice to several alcohols and drugs of abuse. PMID- 1632614 TI - Ethanol produces rapid biphasic hedonic effects. PMID- 1632615 TI - Dramatic depletion of mesolimbic extracellular dopamine after withdrawal from morphine, alcohol or cocaine: a common neurochemical substrate for drug dependence. PMID- 1632617 TI - Morphine withdrawal in the hamster. PMID- 1632616 TI - System of aldehyde metabolism in brain of rats during development of tolerance to the hypnotic effect of ethanol. PMID- 1632618 TI - Weak base model of amphetamine action. PMID- 1632619 TI - Methylxanthines (caffeine and theophylline) blocked methamphetamine-induced conditioned place preference in mice but enhanced that induced by cocaine. PMID- 1632620 TI - Comparison of evoked potentials in men and women admitted for alcohol detoxification. PMID- 1632621 TI - Vasopressin system is impaired in rat offspring prenatally exposed to chronic nicotine. PMID- 1632622 TI - A state by state picture of the changing practice of dentistry in the 1980s. AB - A review is provided of the changing practice of dentistry at the state level. Emphasis is placed on the economics and ownership of practice, and the evolving gender and specialist composition of the profession. PMID- 1632623 TI - Denture hyperplasia and oncocytic metaplasia. AB - A case of denture hyperplasia of the upper labial sulcus with concomitant oncocytic metaplastic changes is described. The patient concerned is an elderly male wearing an ill-fitting upper full denture. PMID- 1632624 TI - Leiomyoma of the incisive papilla region: a case report. AB - Leiomyomas are benign neoplasms of smooth muscle origin. They represent rare entities in the oral cavity. A case arising from the incisive papilla region of a 3-month-old infant is described and the histogenesis as well as the biologic potential of this tumor are discussed. PMID- 1632625 TI - Central mucoepidermoid carcinoma of the jaws. Review of the literature and case report. AB - A CMEC which occurred within the right maxillary canine-third molar region of a 34-year-old male was presented. The clinical symptoms were swelling and pain. Radiologically the lesion looked like an ameloblastoma or residual cyst. Hemimaxillectomy was the treatment. No evidence of recurrence has been observed for ten months after the operation. PMID- 1632626 TI - The Sturge-Weber syndrome: a case involving a 13-year-old black male. AB - A 13-year-old black male patient with Sturge-Weber Syndrome is presented. The report describes the classic presentation of the syndrome, emphasizing the oral manifestations. The case presentation includes a discussion of the differential diagnosis of gingival enlargement, and suggestions for subsequent therapy. PMID- 1632627 TI - Nifedipine-induced gingival hyperplasia. AB - Gingival hyperplasia is an adverse reaction of nifedipine therapy. Oral manifestations of this condition include enlarged and painful gingiva accompanied by spontaneous bleeding. Nifedipine-induced gingival hyperplasia may be reversible once a proper drug substitution is made. Two cases of gingival hyperplasia resulting from nifedipine are described and the drug's possible mode of action is discussed. PMID- 1632628 TI - Localization of impacted teeth utilizing inherent panoramic distortions. AB - Distortions in the size of images seen on panoramic radiographs can assist the clinician in determining the site of impacted teeth in relation to the dental arch. Application of this principle can often eliminate the necessity for additional radiographic views and prevent exposure of the patient to unnecessary radiation. PMID- 1632629 TI - Hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol by rat prostate microsomes: effects of antibodies and chemical inhibitors of cytochrome P450 enzymes. AB - The purpose of the present study was to test the hypothesis that rat prostate microsomes contain a single cytochrome P450 enzyme responsible for the conversion of 5 alpha-androstane-3 beta,17 beta-diol to a series of trihydroxylated products. The three major metabolites formed by in vitro incubation of 5 alpha [3H]androstane-3 beta,17 beta-diol with rat prostate microsomes were apparently 5 alpha-androstane-3 beta,6 alpha,17 beta-triol, 5 alpha-androstane-3 beta,7 alpha,17 beta-triol, and 5 alpha-androstane-3 beta,7 beta,17 beta-triol, which were resolved and quantified by reverse-phase HPLC with a flow through radioactivity detector. The ratio of the three metabolites remained constant as a function of incubation time, microsomal protein concentration, ionic strength, and substrate concentration. The ratio of the three metabolites was dependent on pH, apparently because the hydroxylation of 5 alpha-androstane-3 beta,17 beta diol shifted from the 6 alpha- to the 7 alpha-position with increasing pH (6.8 8.0). The V(max) values were 380, 160, and 60 pmol/mg microsomal protein/min for the rate of 6 alpha-, 7 alpha-, and 7 beta-hydroxylation, respectively. Similar Km values (0.5-0.7 microM) were measured for enzymatic formation of all three metabolites, which suggests that formation of all three metabolites was catalyzed by a single, high-affinity enzyme. Testosterone, 5 alpha-dihydrotestosterone, and 5 alpha-androstane-3 alpha,17 beta-diol did not appreciably inhibit the hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol, suggesting that this enzyme exhibits a high degree of substrate specificity. Formation of all three metabolites was inhibited by antibody against rat liver NADPH-cytochrome P450 reductase (85%) and by a 9:1 mixture of carbon monoxide and oxygen (60%). Several chemical inhibitors of cytochrome P450 enzymes, especially the antimycotic drug clotrimazole, also inhibited the formation of all three metabolites. Polyclonal antibodies that recognize liver cytochrome P450 1A, 2A, 2B, 2C, and 3A enzymes did not inhibit 5 alpha-androstane-3 beta,17 beta-diol hydroxylase activity. Overall, these results are consistent with the hypothesis that the 6 alpha-, 7 alpha-, and 7 beta-hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol by rat prostate microsomes is catalyzed by a single, high-affinity P450 enzyme. This cytochrome P450 enzyme appears to be structurally distinct from those in the 1A, 2A, 2B, 2C, and 3A gene families. PMID- 1632630 TI - Hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol by rat prostate microsomes: potent inhibition by imidazole-type antimycotic drugs and lack of inhibition by steroid 5 alpha-reductase inhibitors. AB - 5 alpha-Dihydrotestosterone, the principal androgen mediating prostate growth and function in the rat, is formed from testosterone by steroid 5 alpha-reductase. The inactivation of 5 alpha-dihydrotestosterone involves reversible reduction to 5 alpha-androstane-3 beta,17 beta-diol by 3 beta-hydroxysteroid oxidoreductase followed by 6 alpha-, 7 alpha-, or 7 beta-hydroxylation. 5 alpha-Androstane-3 beta,17 beta-diol hydroxylation represents the ultimate inactivation step of dihydrotestosterone in rat prostate and is apparently catalyzed by a single, high affinity (Km approximately 0.5 microM) microsomal cytochrome P450 enzyme. The present studies were designed to determine if 5 alpha-androstane-3 beta,17 beta diol hydroxylation by rat prostate microsomes is inhibited by agents that are known inhibitors of androgen-metabolizing enzymes. Inhibitors of steroid 5 alpha reductase (4-azasteroid analogs; 10 microM) or inhibitors of 3 beta hydroxysteroid oxidoreductase (trilostane, azastene, and cyanoketone; 10 microM) had no appreciable effect on the 6 alpha-, 7 alpha-, or 7 beta-hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol (10 microM) by rat prostate microsomes. Imidazole-type antimycotic drugs (ketoconazole, clotrimazole, and miconazole; 0.1 10 microM) all markedly inhibited 5 alpha-androstane-3 beta,17 beta-diol hydroxylation in a concentration-dependent manner, whereas triazole-type antimycotic drugs (fluconazole and itraconazole; 0.1-10 microM) had no inhibitory effect. The rank order of inhibitory potency of the imidazole-type antimycotic drugs was miconazole greater than clotrimazole greater than ketoconazole. In the case of clotrimazole, the inhibition was shown to be competitive in nature, with a Ki of 0.03 microM. The imidazole-type antimycotic drugs inhibited all three pathways of 5 alpha-androstane-3 beta,17 beta-diol hydroxylation to the same extent, which provides further evidence that, in rat prostate microsomes, a single cytochrome P450 enzyme catalyzes the 6 alpha-, 7 alpha-, and 7 beta hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol. These studies demonstrate that certain imidazole-type compounds are potent, competitive inhibitors of 5 alpha-androstane-3 beta,17 beta-diol hydroxylation by rat prostate microsomes, which is consistent with the effect of these antimycotic drugs on cytochrome P450 enzymes involved in the metabolism of other androgens and steroids. PMID- 1632631 TI - Formation of intraprotamine disulfides in vitro. AB - When mammalian protamine is dissolved in aqueous buffers at neutral or alkaline pH, both ends of the protein fold inward toward the center of the molecule and form disulfide crosslinks that stabilize several different structures. In the absence of reducing agents, these folded forms of protamine may be visualized and quantitated by gel electrophoresis. Using this technique, we have examined the formation of bull protamine disulfides in solution and describe a variety of factors that affect this process. At pH 8, disulfide-stabilized folded forms of protamine appear within minutes after solubilization of the fully reduced protein. Five different monomers are detected by electrophoresis. Each of these monomers is stabilized by at least one disulfide crosslink and migrates with a distinct mobility, ahead of the fully reduced and extended protein. Under certain conditions, dimers of these folded structures crosslinked by interprotamine disulfides are also formed. The appearance of these disulfide-crosslinked forms of protamine is effected by air oxidation, accelerated at alkaline pH, inhibited upon lowering the pH below pH 7 and eliminated by modifying the protein's cysteine residues. Similar intramolecular disulfides are also produced after the protamine molecule binds to DNA. These results suggest that only those cysteines located within the amino- and carboxyterminal ends of the protein appear to participate in forming intramolecular disulfides in vitro. PMID- 1632632 TI - Tissue-specific binding of testis nuclear proteins to a sequence element within the promoter of the testis-specific histone H1t gene. AB - The rat histone H1t gene is transcribed only in testis germinal cells. This testis-specific chromosomal protein is first synthesized during spermatogenesis in pachytene spermatocytes and the entire complement of testis histones is replaced during the midspermatid stage of spermiogenesis by positively charged transition nuclear proteins TP1 and TP2. Mobility shift assays conducted using crude nuclear protein extracts from different tissues and an 18-bp DNA sequence element within the H1t promoter as a probe reveal binding only with nuclear proteins from testis. The binding is specifically competed with an excess of the same unlabeled DNA fragment but not with heterologous competitors. A larger oligonucleotide corresponding to the same sequence element plus 18 bp of the adjacent downstream H1/CCAAT element binds nuclear proteins from all tissues tested, but a unique low mobility band is formed only with testis extracts. Protein-DNA crosslinking experiments reveal that two major polypeptides with molecular weights of approximately 13 and 30 kDa bind to the 18-bp H1t promoter sequence element. This strong correlation between the tissue where the H1t gene is transcribed and the presence of testis-specific nuclear proteins that bind to a sequence element within the testis histone H1t promoter supports the possibility that these DNA-binding proteins may participate in formation of an active transcription initiation complex with the testis H1t promoter. PMID- 1632633 TI - Properties of monoglycerol acyltransferase in rat adipocytes. AB - Previous studies by Coleman and Haynes (1986, J. Biol. Chem. 261, 224-228) indicated the presence of two different tissue specific monoacylglycerol acyltransferases (MGAT) in intestinal mucosa and suckling rat liver. The evidence was based upon the differential responses of these two isoenzymes to various treatments including, the effects of temperature, proteolysis, protein modification reagents, detergents, and divalent cations. In the present investigation, we have used some of these criteria to determine the identity of adipose enzyme with the MGAT present in liver and intestinal microsomes. The properties of adipose and intestinal enzymes were similar in several respects, but differed from the liver enzyme. This suggests the possibility that MGAT activities from adipose and intestine may be mediated by the same enzyme protein, whereas the liver MGAT may be a separate isoenzyme as proposed earlier. The most distinguishing feature of the liver enzyme was its ability to sustain both high temperature (52 degrees C) and resist proteolysis. However, when disrupted microsomal preparations were used, the liver enzyme was both thermolabile and protease sensitive, as observed for the intestinal and adipose MGAT. Possibly, the location of liver MGAT within the membranes may be responsible for such unique properties of liver MGAT. PMID- 1632634 TI - Thrombin-activated and factor Xa-activated human factor VIII: differences in cofactor activity and decay rate. AB - The decay of human coagulation factor VIIIa has been studied by kinetic methods that ensure no interference through proteolytic feedback. The rate of decay of factor VIIIa activity was found to vary with the activator used to activate factor VIII. Thrombin-activated factor VIII-von Willebrand factor complex (fVIII vWf) decayed at a rate of 0.31 min-1, whereas factor Xa-activated fVIII-vWf decayed at 0.11 min-1 under the same conditions. Factor VIII free of von Willebrand factor (factor VIII: C), although decaying at a generally slower rate after activation, still showed a dependence of decay rate on activator: thrombin activated factor VIII:C decaying at a rate of 0.06 min-1, and factor Xa-activated factor VIII: C at 0.01 min-1. Readdition of von Willebrand factor (18 micrograms/ml) to factor VIII:C did not alter the observed activity or decay rate. The decay of the two species of factor VIIIa was studied, using the fVIIIa vWf complex, in the presence of varying levels of factor IXa. Plots of reciprocal decay rates vs factor IXa concentration were linear, and nearly parallel for the two factor VIIIa species, with a mean slope of 0.56 min.nM-1. In addition to these studies, we have confirmed previous studies showing that the two forms of factor VIIIa differ in cofactor activity, but they do so in the same ratio as in their decay rates. We suggest that this difference and that observed in decay rate have a common cause, and incorporate this into a potential kinetic model of factor VIII activation and decay. PMID- 1632635 TI - Esterase-1: developmental expression in the mouse and distribution of related proteins in other species. AB - Esterase 1 (Es-1) is a sexually dimorphic 65-kDa glycoprotein present in plasma and other murine tissues able to hydrolyze a variety of esters including fatty acid esters of estradiol. Like most other carboxylesterases, its function is unknown. To gain insight into the function of Es-1 and by analogy other carboxylesterases, we have examined the developmental regulation of Es-1 in the mouse and have looked for the presence of related proteins in the plasma of other species. Northern blot analysis of total RNA from the livers of mice of various ages using a 32P-labeled 470-bp Es-1 cDNA probe showed clear postpartum induction with no detectable Es-1 mRNA in fetal liver. Similarly, immunoblotting after sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an affinity purified rabbit antibody to Es-1 showed no cross-reacting proteins in the plasma until after birth. Northern blot analysis of total RNA from a variety of adult mouse tissues showed the presence of substantial levels of Es-1 mRNA only in liver with lower levels in kidney, testes, and ovaries. Liver mRNA and plasma protein levels rose in parallel attaining full adult levels between 15 and 20 days of age. When plasma proteins were electrophoresed on 7% polyacrylamide gels under nondenaturing conditions, the antibody to Es-1 recognized a low mobility protein in mouse, rat, human, baboon, guinea pig, bovine, horse, and canine but not in chicken plasma. Consistent with the immunoblotting results, the Es-1 cDNA probe hybridized to restriction fragments from human, monkey, rat, and rabbit as well as mouse genomic DNA but not from chicken DNA indicating conservation of the esterase (or esterase-like) gene in mammalian species. The low mobility antigens in mouse and human plasma appeared also to cross-react with antibodies to human thyroglobulin, although antibodies to human thyroglobulin did not appear to recognize Es-1 under these conditions. PMID- 1632636 TI - Purification and characterization of a novel 12,000-Da calcium binding protein from smooth muscle. AB - A new low molecular weight calcium binding protein, designated 12-kDa CaBP, has been isolated from chicken gizzard using a phenyl-Sepharose affinity column followed by ion-exchange and gel filtration chromatographies. The isolated protein was homogeneous and has a molecular weight of 12,000 based on sodium dodecyl sulfate-gel electrophoresis. The amino acid composition of this protein is similar to but distinct from other known low molecular weight Ca2+ binding proteins. Ca2+ binding assays using Arsenazo III (Sigma) indicated that the protein binds 1 mol of Ca2+/mol of protein. The 12-kDa CaBP underwent a conformational change upon binding Ca2+, as revealed by uv difference spectroscopy and circular dichroism studies in the aromatic and far-ultraviolet range. Addition of Ca2+ to the 12-kDa CaBP labeled with 2-p-toluidinylnaphthalene 6-sulfonate (TNS) resulted in a sevenfold increase in fluorescence intensity, accompanied by a blue shift of the emission maximum from 463 to 445 nm. Hence, the probe in the presence of Ca2+ moves to a more nonpolar microenvironment. Like calmodulin and other related Ca2+ binding proteins, this protein also exposes a hydrophobic site upon binding calcium. Fluorescence titration with Ca2+ using TNS labeled protein revealed the presence of a single high affinity calcium binding site (kd approximately 1 x 10(-6) M). PMID- 1632637 TI - Catalysis of the oxidation of steroid and stilbene estrogens to estrogen quinone metabolites by the beta-naphthoflavone-inducible cytochrome P450 IA family. AB - Diethylstilbestrol (DES) or catecholestrogens are metabolized by microsomal enzymes to quinones, DES Q or catecholestrogen quinones, respectively, which have been shown to bind covalently to DNA and to undergo redox cycling. The isoforms of cytochrome P450 catalyzing this oxidation of estrogens to genotoxic intermediates were not known and have been identified in this study by (a) using microsomes of rats treated with various inducers of cytochrome P450; (b) using purified cytochrome P450 isoforms; and (c) examining the peroxide cofactor concentrations necessary for this oxidation by microsomes or pure isoenzymes. The highest rate of oxidation of DES to DES Q was obtained using beta-naphthoflavone induced microsomes (14.0 nmol DES Q/mg protein/min) or cytochrome P450 IA1 (6.4 pmol DES Q/min/pmol P450). Isosafrole-induced microsomes or cytochrome P450 IA2 oxidized DES to quinone at one-third or one-fifth of that rate, respectively. Low or negligible rates of oxidation were measured when oxidations were catalyzed by microsomal rat liver enzymes induced by phenobarbital, ethanol, or pregnenolone 16 alpha-carbonitrile or by pure cytochromes P450 IIB1, IIB4, IIC3, IIC6, IIE1, IIE2, IIG1, or IIIA6. Cytochrome P450 IA1 also catalyzed the oxidation of 2- or 4 hydroxyestradiol to their corresponding quinones. The beta-naphthoflavone-induced microsomes and cytochrome P450 IA1 had the highest "affinity" for cumene hydroperoxide cofactor (Km = 77 microM). Cofactor concentrations above 250 microM resulted in decreased rates of oxidation. The other cytochrome P450 isoforms required much higher cofactor concentrations and were not inactivated at high cofactor concentrations. The data demonstrate that beta-naphthoflavone-inducible cytochrome P450 IA family enzymes catalyze most efficiently the oxidation of estrogenic hydroquinones to corresponding quinones. This oxidation may represent a detoxification pathway to keep organic hydroperoxides at minimal concentrations. The resulting quinone metabolites may be detoxified by other pathways. However, in cells with decreased detoxifying enzyme activities, quinones metabolites may accumulate and initiate carcinogenesis or cell death by covalent arylation of DNA or proteins. PMID- 1632638 TI - 1,2-Diacylglycerol does not mediate the stimulatory effect of phorbol 12 myristate 13-acetate on phosphatidylcholine synthesis in NIH 3T3 fibroblasts. AB - In HeLa cells, increased 1,2-diacylglycerol (1,2-DAG) has been suggested to mediate the stimulatory effect of phorbol 12-myristate 13-acetate (PMA) on phosphatidylcholine (PtdCho) biosynthesis (A. K. Utal, H. Jamil, and D. E. Vance, 1991, J. Biol. Chem. 266, 24,084-24,091). The aim of this study was to examine if 1,2-DAG might have a similar mediatory role in NIH 3T3 fibroblasts. In these cells, PMA-induced hydrolysis of PtdCho and the formation of secondary product 1,2-DAG was inhibited by exposing the cells to either 300 mM ethanol for 15 min (less than 80% inhibition) or 43 degrees C for 60 min (less than 50% inhibition). In contrast, neither ethanol nor heat-treatment caused significant inhibition of PMA-stimulated PtdCho synthesis. These data indicate that in NIH 3T3 fibroblasts, 1,2-DAG is not a mediator of the stimulatory action of PMA on PtdCho synthesis. PMID- 1632639 TI - Kinetic mechanism of the cytosolic malic enzyme from human breast cancer cell line. AB - The kinetic mechanism of the cytosolic NADP(+)-dependent malic enzyme from cultured human breast cancer cell line was studied by steady-state kinetics. In the direction of oxidative decarboxylation, the initial-velocity and product inhibition studies indicate that the enzyme reaction follows a sequential ordered Bi-Ter kinetic mechanism with NADP+ as the leading substrate followed by L malate. The products are released in the order of CO2, pyruvate, and NADPH. The enzyme is unstable at high salt concentration and elevated temperature. However, it is stable for at least 20 min under the assay conditions. Tartronate (2 hydroxymalonate) was found to be a noncompetitive inhibitor for the enzyme with respect to L-malate. The kinetic mechanism of the cytosolic tumor malic enzyme is similar to that for the pigeon liver cytosolic malic enzyme but different from those for the mitochondrial enzyme from various sources. PMID- 1632640 TI - Stimulation by heme of steryl ester synthase and aerobic sterol exclusion in the yeast Saccharomyces cerevisiae. AB - Saccharomyces cerevisiae sterol and heme auxotrophs were used to elucidate a role for hemes in sterol esterification. Steryl ester synthase (SES) activity was stimulated on average fourfold in cells supplemented with 50 micrograms/ml delta aminolevulinic acid (ALA). This stimulation was not dependent on ALA per se, but on the ability of this precursor to effect heme competency. The addition of ALA stimulated SES activity of yeast on either fermentative or respiratory carbon sources. The elevation of SES activity was independent of intracellular free sterol, unsaturated fatty acid, or methionine levels. SES activity increases as the cells enter stationary phase, and this increase is enhanced by heme competency. SES was directly inhibited by the hypocholesterolemic drug lovastatin (mevinolin). The inhibition of SES activity by lovastatin was enhanced in heme competent cells. PMID- 1632641 TI - Indole protects tryptophan indole-lyase, but not tryptophan synthase, from inactivation by trifluoroalanine. AB - Trifluoroalanine is a mechanism-based inactivator of Escherichia coli tryptophan indole-lyase (tryptophanase) and E. coli tryptophan synthase (R. B. Silverman and R. H. Abeles, 1976, Biochemistry 15, 4718-4723). We have found that indole is able to prevent inactivation of tryptophan indole-lyase by trifluoroalanine. The protection of tryptophan indole-lyase by indole exhibits saturation kinetics, with a KD of 0.03 mM, which is comparable to the KI for inhibition of pyruvate ion formation (0.01 mM) and the Km for L-tryptophan synthesis. Fluoride electrode measurements indicate the formation of 28 mol of fluoride ion per mole of enzyme during inactivation of tryptophan indole-lyase, and 121 mol of fluoride ion are formed per mole of enzyme in the presence of 2 mM indole during the same incubation period. 19F NMR spectra of reaction mixtures of tryptophan indole lyase and trifluoroalanine showed evidence only for fluoride ion formation, in either the absence or the presence of indole, and difluoropyruvic acid was not detected. The partition ratio, kcat/kinact, is estimated to be 9. Tryptophan indole-lyase in the presence of trifluoroalanine exhibits visible absorption peaks at 446 and 478 nm, which decay at the same rate as inactivation. However, in the presence of 1 mM indole and trifluoralanine, tryptophan indole-lyase exhibits a peak only at 420 nm, and the spectra show a gradual increase at 300 310 nm with incubation. In contrast, tryptophan synthase is not protected by indole from inactivation by trifluoroalanine, and the absorption peak at 408 nm for the tryptophan synthase-trifluoroalanine complex is unaffected by indole. These results demonstrate that inactivation of tryptophan indole-lyase occurs via a catalytically competent species, probably the beta,beta-difluoro-alpha aminoacrylate intermediate, which can be partitioned from inactivation to products by a reactive aromatic nucleophile, indole. PMID- 1632642 TI - Purification, molecular cloning, and expression of lipase from Pseudomonas aeruginosa. AB - An extracellular lipase secreted by Pseudomonas aeruginosa TE3285 was purified. A genomic library of this strain was constructed in lambda EMBL3, and a DNA fragment 2.7 kb long containing the lipase gene, lipA, was isolated with an oligonucleotide probe synthesized on the basis of the partial amino acid sequence of a purified preparation of the enzyme. Nucleotide sequence analysis showed an open reading frame of 933 bases, and the deduced amino acid sequence agreed well with the molecular mass and partial amino acid sequences of mature lipase. The results of alignment of the amino acid sequences of five lipases from Pseudomonas species considered together with the published crystal structure studied with human pancreatic lipase showed that Ser82, His251, and Asp209 were catalytic residues and that a surface loop from residues 172 to 204 was responsible for the substrate specificity. About 50 bases downstream of lipA, there was another gene, lipB. The sequence of lipB was highly homologous to that of putative modulators of the production of active lipases in other Pseudomonas species. Expression plasmids encoding lipA followed by the complete or incomplete lipB gene downstream of the lac promoter of pUC18 were constructed. lipA was expressed in Escherichia coli 1100 only in the presence of the complete lipB gene. PMID- 1632643 TI - Binding of Saccharomyces cerevisiae extracellular proteins to glucane. AB - Interactions of Saccharomyces cerevisiae cell wall proteins with purified yeast glucane were studied. Using the beta-glucanase (BGL2 gene product) as the model cell wall protein, strong binding to glucane was demonstrated at pH lower than 7, while at pH higher than 8 the reaction did not occur. NaCl (2 M) did not influence the binding, while urea in concentrations higher than 4 M affected the interactions. It was also found that most other cell wall proteins, as well as intracellular proteins, reacted with glucane in the same way, showing that the interactions of proteins with glucane are rather nonspecific. Soluble periplasmic proteins invertase and acid phosphatase failed to react with glucane under the same conditions, indicating that these proteins have certain structural features preventing their interactions with glucane. PMID- 1632644 TI - Topical tocopherol acetate reduces post-UVB, sunburn-associated erythema, edema, and skin sensitivity in hairless mice. AB - Exposure of the skin of the back of skh-1 hairless mice to UVB (310 nm peak) irradiation at doses of 0.115-0.23 J/cm2 results after 24-48 h in an erythema which can be quantified using an erythema meter, providing a useful model of sunburn. Application of pure d-alpha-tocopherol acetate, a thick oil, to the skin immediately following the exposure to UVB significantly reduces the increase in erythema index, by 40-55%. At the lower dose (0.115 J/cm2), skin thickness (associated with edematous swelling of the sunburned skin) was measured by a novel non-invasive technique not previously reported for this purpose--magnetic resonance imaging (MRI). In two experiments the UVB-induced increase in skin thickness was significantly reduced at 24 hr by 29 and 54%, and at 48 hr by 26 and 61%. After 8 days the untreated irradiated mouse skin still showed a significant increase in thickness (24%) compared to the untreated unirradiated control, while the treated irradiated control was not significantly thicker than the unexposed control. Skin sensitivity was tested using a modification of the technique of esthesiometry, by observing rapid avoidance responses of the mouse to a pressure of 0.96 g/cm2 exerted by applying to the skin the tip of a nylon esthesiometer fiber extended to 60 mm in length. The untreated irradiated mice were more sensitive (p less than 0.07, Wilcoxon test) than the treated irradiated mice, and also significantly different from the untreated unirradiated control mice (p less than 0.04, Wilcoxon test), but the treated irradiated mice were not significantly differently sensitive when compared to the unirradiated controls (p less than 0.32). Taken together these data indicate that the erythema, edema, and skin sensitivity commonly associated with UVB-induced sunburn are significantly reduced by topical application of tocopherol acetate even after the exposure has occurred. This observation suggests that treatment of sunburn may be possible even after the irradiation has stopped, by a derivative of d-alpha-tocopherol which is stable to autooxidation. PMID- 1632645 TI - The binding of estrogen and estrogen antagonists to the estrogen receptor. AB - The model of the estrogen receptor as a dimer of identical, interacting subunits and data obtained by Sasson and Notides (1988, Mol. Endocrinol. 2, 307-312) were used to find the standard free energy changes that describe the binding of estradiol and 4-hydroxytamoxifen to the estrogen receptor. For the binding of estradiol or 4-hydroxytamoxifen to the estrogen receptor the data do not deviate systematically from the best fit to the model. The standard free energy change for binding of one molecule of estradiol at one site and one molecule of 4 hydroxytamoxifen at the second site of estrogen receptor indicates that 4 hydroxytamoxifen antagonizes the binding of estradiol to the estrogen receptor. PMID- 1632647 TI - Structural analysis of five new monosialylated oligosaccharides from human milk. AB - The total monosialylated oligosaccharide fraction from pooled human milk was isolated by gel filtration and ion-exchange chromatography. Further separation by HPLC using a mobile phase containing an ion-pairing reagent of triethylamine gave five new monosialylated oligosaccharides. Structural analysis was carried out by chemical analyses, fast atom bombardment mass spectrometry, and 500-MHz NMR spectroscopy. Combined structural data revealed the following new structures: [formula: see text] PMID- 1632646 TI - Lipid peroxidation, antioxidant concentrations, and fatty acid contents of muscle tissue from malignant hyperthermia-susceptible swine. AB - Homogenates of semitendinosus muscle from malignant hyperthermia (MH)-susceptible pigs produced threefold more pentane than those from MH-resistant pigs, indicating enhanced free radical-mediated peroxidation of n-6 fatty acids. This did not reflect a deficiency in tissue antioxidants or antioxidant-enzymes but glutathione concentrations and glutathione peroxidase activities were increased in the tissue from MH-susceptible swine, consistent with an adaptive response to a sustained oxidant stress. A lower proportion of linoleic acid (18:2 n-6) in phospholipids and neutral lipids in muscle from MHS pigs indicated increased peroxidation or metabolism (desaturation and elongation). The increased oleic acid (18:1 n-9) in the MHS muscle indicated that desaturase activity was elevated in all lipid classes. The results are consistent with the hypothesis that enhanced free radical activity and lipid peroxidation contributes to the abnormalities in Ca2+ homeostasis and polyunsaturated fatty acid metabolism in MH. PMID- 1632648 TI - Activation of rat liver microsomal glutathione S-transferase by hydrogen peroxide: role for protein-dimer formation. AB - The mechanism of oxygen radical-dependent activation of hepatic microsomal glutathione S-transferase by hydrogen peroxide was studied. Glutathione S transferase activity in liver microsomes was increased 1.5-fold by incubation with 0.75 mM hydrogen peroxide at 37 degrees C for 10 min, and the increase in activity was reversed by incubation with dithiothreitol. Purified glutathione S transferase was also activated by hydrogen peroxide after incubation at room temperature, and the increase in the activity was also reversed by dithiothreitol. Immunoblotting with anti-microsomal glutathione S-transferase antibodies after sodium dodecyl sulfate-polyacrylamide gel electrophoresis of hydrogen peroxide-treated microsomes or purified glutathione S-transferase revealed the presence of a glutathione S-transferase dimer. These results indicate that the hydrogen peroxide-dependent activation of the microsomal glutathione S-transferase is associated with the formation of a protein dimer. PMID- 1632649 TI - Purification and characterization of a putative proenkephalin cleaving enzyme. AB - A putative proenkephalin-cleaving enzyme (PCE) extracted from bovine adrenal chromaffin granules was purified with soybean trypsin inhibitor high-performance affinity chromatography. The 12,600-fold purified enzyme was maximally active at pH 8.0. The enzyme was completely inhibited with lima bean trypsin inhibitor (0.1 mg/ml), soybean trypsin inhibitor (0.1 mg/ml), and p (chloromercuri)benzenesulfonic acid (1.0 mM), indicating PCE is a serine protease with cysteine residues likely to be involved in its structure or activity. It exhibited significant autoproteolysis without specific substrates present. The substrate specificity and kinetic constants with the enkephalin-containing (EC) peptides Leu-9 and proenkephalin Peptides B, E, and F as substrates were studied. The cleavage patterns were substantially different than with trypsin digestion. PCE specifically recognized the paired basic amino acid residues and predominantly cleaved the peptide bonds between Lys and Arg sites and peptide bonds after Lys-Lys and Arg-Arg sites. Different Km and Vmax values for the different Lys-Arg sites indicate sequences in addition to the paired basic residues can affect enzyme activity. Also, the lower Km and Vmax of Peptide E suggest a higher affinity for this peptide but much slower cleavage. The C terminally located Lys-Arg site appears responsible for this high affinity. Based on these observations, we propose the following: (a) the primary structure of these peptides contains enough information to be processed correctly by PCE and (b) PCE may be regulated by pH and Peptide E to prevent extensive processing of the intermediate EC peptides which are the major opioid peptides found in the adrenal chromaffin granules. PMID- 1632650 TI - The lysosomal membrane glycoprotein lamp-1 is transported to lysosomes by two alternative pathways. AB - It has been demonstrated that lysosomal membrane proteins are directed to lysosomes by a tyrosine-containing structural motif in their cytoplasmic tails. It is presently unclear whether lysosomal membrane proteins are directly transported to lysosomes or first taken to the plasma membrane and then directed to the lysosomes via the endocytic pathway. In the present study, the transport pathways taken by one of the members of highly glycosylated lysosomal membrane proteins, lamp-1, were examined in human HL-60 cells. Pulse-chase labeling, combined with cell surface biotinylation and Percoll density gradient fractionation, was used to measure the kinetics of transport to the cell surface and lysosomes. The results show that the majority of lamp-1 is directly transported to lysosomes by a fast pathway (half-time 60 min), which involves sorting at an intracellular site, presumably in the trans-Golgi network. A minor part of lamp-1 is transported out to the cell surface, where it is internalized and eventually delivered to lysosomes. Transport by this pathway requires a long transit time (half-time greater than 2 h). After granulocytic differentiation of HL-60 cells by dimethyl sulfoxide, the synthesis of lamp-1 was increased approximately twofold. In these cells, the sorting in the Golgi apparatus is more effective, leaving only a minute fraction of lamp-1 for the bulk flow to the cell surface. This study establishes that the majority of lamp-1 is directly transported to lysosomes and that, in certain cells, the minority of the molecules is transported to lysosomes via the cell surface. PMID- 1632651 TI - A possible in vivo mechanism of intermediate transfer by glycolytic enzyme complexes: steady state fluorescence anisotropy analysis of an enzyme complex formation. AB - Rate constants of dissociation (k(off)) and association (k(on)) of the bienzyme complex yeast glyceraldehyde-3-phosphate dehydrogenase--yeast alcohol dehydrogenase have been determined in the absence and presence of NAD or NADH by fluorescence anisotropy measurements. We found that dissociation of the complex is considerably slower than catalytic turnover of either of the enzymes (that is k(off) much less than kcat) irrespective of the presence of coenzymes. A perusal of the literature reveals that this relation invariably applies to all systems studied so far. These observations all taken together constitute compelling evidence that direct metabolite transfer in enzyme complexes cannot be satisfactorily described by invoking the dynamic model but requires a model assuming more lasting complexes. This seems to support the case of the temporary stationary model suggested by one of us. Implications of this conclusion are treated in depth and further evidence is cited under Discussion. PMID- 1632652 TI - Production and characterization of recombinant lignin peroxidase isozyme H2 from Phanerochaete chrysosporium using recombinant baculovirus. AB - Recombinant Phanerochaete chrysosporium lignin peroxidase isozyme H2 (pI 4.4) was produced in insect cells infected with a genetically engineered baculovirus containing a copy of the cDNA clone lambda ML-6. The recombinant enzyme was purified to near homogeneity and is capable of oxidizing veratryl alcohol, iodide, and, to a lesser extent, guaiacol. The Km of the recombinant enzyme for veratryl alcohol and H2O2 is similar to that of the fungal enzyme. The guaiacol oxidation activity or any other activity is not dependent upon Mn2+. The purified recombinant peroxidase is glycosylated with N-linked carbohydrate(s). The recombinant lignin peroxidase eluted from an anion exchange resin similar to that of native isozyme H1 rather than H2. However, the pI of the recombinant enzymes is different from both H1 and H2 isozymes. Further characterization of native isozymes H1 and H2 from the fungal cultures revealed identical N-terminus residues. This indicates that isozymes H1 and H2 differ in post-translational modification. PMID- 1632653 TI - Coordinated regulation of cerebral glycolytic and oxidative metabolism, mediated by mitochondrially bound hexokinase dependent on intramitochondrially generated ATP. AB - Hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) of rat brain mitochondria is associated with membrane regions thought to correspond to contact sites (regions of close interaction of the inner and outer mitochondrial membranes). Two intramitochondrial compartments of ATP also appear to be located at contact sites, and are dependent on oxidative phosphorylation for their generation. Neither of these compartments was associated with the intermembranal space containing adenylate kinase, nor was there detectable intramitochondrial compartmentation of ATP generated by the adenylate kinase reaction. Formation of these compartments was not dependent on the presence of bound hexokinase since equivalent amounts of compartmented ATP were found in mitochondria from which a major portion of the hexokinase had been removed by treatment with Glc-6-P. During active oxidative phosphorylation, mitochondrially bound hexokinase is totally dependent upon intramitochondrially compartmented ATP as a substrate. Both the levels of ATP in the intramitochondrial compartments and the rate of glucose phosphorylation by mitochondrially bound hexokinase were shown to be correlated with the rate of oxidative phosphorylation. This dependence of hexokinase on intramitochondrial ATP levels that reflect the status of mitochondrial oxidative metabolism provides a mechanism by which hexokinase can serve as a mediator, coordinating the rate at which glucose is introduced into the glycolytic pathway with terminal oxidative stages of metabolism and avoiding the accumulation of lactate which has been associated with toxic effects on the brain. PMID- 1632655 TI - Inhibition of human serine proteases by substituted 2-azetidinones. AB - trans-4-Ethoxycarbonyl-3-ethyl-1-(4-nitrophenyl-sulfonyl)-azetidin -3-one described by Firestone et al. (1990, Tetrahedron 46, 2255) as an inhibitor of human leucocyte elastase (HLE) displayed potent, time-dependent inhibition of both HLE and human cathepsin G (Cat-G). The cis-isomer was 7- and 180-fold less active, respectively. The mechanism likely involves opening of the beta-lactam ring by the active site serine to form an acyl-enzyme intermediate(s). This intermediate partitions with ratios of 4:1 between turnover of the inhibitor and formation of relatively stable enzyme-inhibitor complexes from both enzymes. The final HLE-inhibitor complex reactivated with a half-life of 48 h at 25 degrees C and was 16-fold more stable than the Cat-G-inhibitor complex. The stability of the acyl-enzymes supports a "double hit" chemical mechanism involving both serine acylation and alkylation of the histidine. These observations suggest that beta lactams may be developed as a class of serine protease inhibitors. PMID- 1632654 TI - ATP-Mg/Pi carrier activity in rat liver mitochondria. AB - The ATP-Mg/Pi carrier in liver mitochondria is activated by micromolar Ca2+ and mediates net adenine nucleotide transport into and out of the mitochondrial matrix. The purpose of this study was to characterize certain features of ATP Mg/Pi carrier activity that are essential for understanding how the mitochondrial adenine nucleotide content is regulated. The relative importance of ATP and ADP as transport substrates was investigated using specific trap assays to measure their separate rates of carrier-mediated efflux with Pi as the external counterion. Under energized conditions ATP efflux accounted for 88% of total ATP+ADP efflux. With oligomycin present to lower the matrix ATP/ADP ratio, ATP efflux was eliminated and ADP efflux was relatively unaffected. Mg2+ was stoichiometrically required for ATP influx and is probably transported simultaneously with ATP. Ca2+ and Mn2+ could substitute for the stoichiometric Mg2+ requirement. ADP influx and Pi-induced adenine nucleotide efflux were unaffected by external Mg2+. Experiments with Pi analogues suggested that Pi is transported as the divalent anion, HPO4(2-). The results show that ATP-Mg and divalent Pi are the major transport substrates; the most probable transport mechanism for the ATP-Mg/Pi carrier is an electroneutral exchange. The results are consistent with the hypothesis that the direction and magnitude of net adenine nucleotide movements are determined mainly by the (ATP-Mg)2- and HPO4(2-) concentration gradients across the inner mitochondrial membrane. PMID- 1632656 TI - Can man's best friend provide clues to the aetiology of systemic lupus erythematosus? PMID- 1632657 TI - Radiographic patterns of osteoarthritis of the knee joint in the community: the importance of the patellofemoral joint. AB - The intimate relation which the patella has with the knee joint and quadriceps muscle suggests that patellofemoral joint osteoarthritis is likely to be an important cause of knee pain and disability. Two hundred and seventy three subjects who reported knee pain in a postal questionnaire survey and 240 control subjects consented to have anteroposterior weightbearing and lateral knee radiographs. Each subject completed a Stanford Health Assessment Questionnaire (HAQ). Radiographic knee osteoarthritis was found in 53% of symptomatic and 17% of asymptomatic subjects. Three patterns predominated patellofemoral, medial, and medial/patellofemoral joint disease in 11, 21, and 7% of the men and in 24, 12, 6% of the women respectively. The occurrence of isolated symptomatic patellofemoral joint osteoarthritis in this sample aged more than 55 years was estimated as 8% in women and 2% in men. All patterns of symptomatic knee joint osteoarthritis increased with age in women but peaked at 70 years in men. Medial joint and patellofemoral joint osteoarthritis were significantly associated with disability (46 v 17% in controls and 64 v 25% in controls respectively) but higher HAQ scores were more common in subjects with patellofemoral joint osteoarthritis. Patellofemoral joint osteoarthritis is common, associated with disability, occurs in the absence of tibiofemoral disease, and can no longer be omitted from future studies of osteoarthritis of the knee joint. PMID- 1632658 TI - Reduction of the concentration and total amount of keratan sulphate in synovial fluid from patients with osteoarthritis during treatment with piroxicam. AB - To study the effects of piroxicam on cartilage metabolism in vivo, a three phase (placebo/piroxicam 20 mg/day by mouth/placebo) double blind controlled trial was conducted in patients with osteoarthritis of the knee joint. Twenty one patients were recruited, 19 of whom (11 women, eight men, median age 70 years) completed the treatment schedule. The knee joint under study was aspirated to dryness at four week intervals. Treatment with piroxicam was accompanied by a decrease in the pain score, an improvement in the functional index, and an increased range of movement. Reductions in the concentration (mean (SEM) 120 (6) to 110 (8) micrograms/ml) and the total amount (1.22 (0.34) to 0.99 (0.37) mg) of keratan sulphate, but not the effusion volume (9.4 (2.5) to 8.3 (2.6) ml) were observed during treatment with piroxicam. These findings are consistent with decreased proteoglycan catabolism during treatment with piroxicam. Neither depressed synthesis nor enhanced clearance of degraded proteoglycan fragments can be excluded, however. PMID- 1632659 TI - Population study of the importance of rheumatoid factor isotypes in adults. AB - Blood samples collected from 13,858 randomly selected subjects participating in a health survey in Iceland from 1974 to 1983 were tested for rheumatoid factor. Samples that were positive in a sensitive RF screening test were analysed further by the Rose-Waaler technique and an isotype specific enzyme linked immunosorbent assay (ELISA). In 1987 the 173 available participants who were RF positive and 156 matched RF negative controls were evaluated clinically for rheumatoid diseases. RF levels and isotype patterns were more persistent in the patients with rheumatoid arthritis (RA) than in RF positive subjects who did not have overt RA. The prevalence of RA was only 19% in the participants who were RF positive in 1987. Forty per cent of the participants who had a persistent (four to 13 years) increase of IgA RF combined with either IgM or IgG RF were diagnosed as having RA. A positive correlation was found between RF levels and various manifestations of RA. This association was stronger for the IgA and IgG RF isotypes than for IgM RF. Excluding RF positivity as a diagnostic parameter, RA was diagnosed in 33 of the participants and 20 (61%) of these patients had increased levels of IgM and IgA RF. Patients with RA with bone erosions in their hands had higher levels of IgA RF than patients without erosions, but an association was not found between bone erosions and other RF isotypes. None of the RF negative participants who were symptom free when the original blood sample was taken developed RA during the four to 13 year follow up period. In contrast, five symptom free RF positive participants developed RA during this period. These five patients had all had increased levels of at least two RF isotypes before the onset of their symptoms. It is concluded that the IgA and IgG RF isotypes have a closer association with the clinical parameters of RA than IgM RF. Furthermore, increases in RF can precede clinical manifestations of RA and this applies in particular to the IgA and IgG RF isotypes. PMID- 1632660 TI - Pathogenic importance of fibronectin in the superficial region of articular cartilage as a local factor for the induction of pannus extension on rheumatoid articular cartilage. AB - To identify the local factors in cartilage that are responsible for the induction of pannus invasion, a 14 day organ culture study in which rheumatoid synovium was grown in contact with cartilage pieces was carried out. Rheumatoid synovium preferentially extended over hyaluronidase treated cartilage pieces, but detached from untreated pieces. Rheumatoid synovium extended over hyaluronidase treated cartilage surfaces containing fibronectin more extensively than over surfaces treated with hyaluronidase only. Extension over hyaluronidase treated cartilage surfaces containing immune complexes was small. The adherence of synovial cells to hyaluronidase treated cartilage slices in vitro was specifically inhibited by the synthetic peptide, Gly-Arg-Gly-Asp-Ser-Pro, which is the adhesive portion of the fibronectin molecule. Furthermore, synovial fibroblast-like cellular extension, morphologically similar to rheumatoid pannus, was observed in the organ culture experiments in which rheumatoid synovium grew over hyaluronidase treated cartilage surfaces containing fibronectin. Synovial tissue extension over fibronectin coated surfaces was inhibited when hyaluronic acid and chondroitin-4 sulphate, major components of cartilage proteoglycans, were present on the cartilage surface. These findings suggest that fibronectin present in the superficial region of cartilage potentiates rheumatoid synovial extension and proteoglycans and immune complexes inhibit rheumatoid synovial extension. It is likely that fibronectin deposited on the eroded surface of articular cartilage induces pannus formation in rheumatoid arthritis. PMID- 1632661 TI - Predictive value of synovial fluid analysis in estimating the efficacy of intra articular corticosteroid injections in patients with rheumatoid arthritis. AB - The predictive relevance of synovial fluid analysis and some other variables for the efficacy of intra-articular corticosteroid injections in 30 patients with rheumatoid arthritis and hydropsy in a knee joint was evaluated in a prospective study. At the onset of the study, the knee joints were aspirated and 30 mg triamcinolone hexacetonide injected intra-articularly. The circumferences and the tenderness scores of the knee joints were measured at onset, after two months, and at the end of the six months' follow up. Of the variables studied, synovial fluid C4, percentage of synovial fluid polymorphonuclear leucocytes, blood haemoglobin, and serum C3 correlated significantly with the decrease in knee joint circumference after two months, whereas only the percentage of synovial fluid polymorphonuclear leucocytes correlated significantly after six months. Between the patients with and without improvement in the tenderness scores of the knee joints, only serum IgM differed at the examination after two months; this was higher in patients whose scores showed no improvement. PMID- 1632662 TI - Effect of fish oil on neutrophil chemiluminescence induced by different stimuli in patients with rheumatoid arthritis. AB - Lipid composition plays an important part in the structural and metabolic functions of cell membranes. In particular the production of inflammatory mediators such as prostaglandins and leukotrienes is dependent on polyunsaturated fatty acid precursors. Neutrophil leucocytes participate in inflammatory processes by their phagocytic and killing activities which can be monitored by measuring the photon emission (chemiluminescence). Chemiluminescence was measured in a luminol dependent system after stimulation by either particulate (zymosan) or soluble (phorbol myristate acetate) stimulus in a group of 10 patients with rheumatoid arthritis before and 21 and 45 days after treatment with a diet supplemented with eicosapentaenoic and docosahexaenoic acids. Ten patients with rheumatoid arthritis continuing their usual diet were used as control subjects. A progressive reduction of chemiluminescence stimulated by zymosan and phorbol myristate acetate was found in the patients treated with fish oil supplementation. This result correlated well with the reduction in erythrocyte sedimentation rate and an improvement of clinical parameters. The effects of fish oil derived lipids on neutrophil chemiluminescence are probably due to a change of the lipid composition of the cell membrane which is dependent on the esterification of eicosapentaenoic acid and docosahexaenoic acid in cellular membrane phospholipids. The modification of membrane lipid composition seems to interact in a non-specific way with the metabolic activation of neutrophils during phagocytosis. PMID- 1632663 TI - Short term effects of intravenous pulses of cyclophosphamide in the treatment of connective tissue disease crisis. AB - A predominantly outpatient regimen of low dose intravenous cyclophosphamide was used to treat patients with serious progressive connective tissue diseases. Fifty five patients were treated with a total of 211 intravenous pulses of cyclophosphamide. Forty five patients had previously shown no response to a variety of other treatments. Low dose intravenous cyclophosphamide (500 mg) was given in 179 pulses and repeated pulses were given in most patients at weekly intervals for one to three weeks to induce disease remission. A good response was noted in 37 of 55 (67%) patients assessed four weeks after the pulses. Only 20 patients needed more than one such course of three pulses of intravenous cyclophosphamide during the observation period. The non-responders were characterised by longstanding disease and irreversible histological findings in renal and muscle biopsy samples. Patients with vasculitis, notably Wegener's granulomatosis, showed the most immediate response, and in most patients the amount of corticosteroids required was markedly reduced. In some patients steroids were completely stopped during the follow up period. The most striking observation of this effective but more conservative regimen was the low incidence of major side effects such as neutropenia and infections. It is concluded that low dose pulses of intravenous cyclophosphamide are well tolerated and are an effective treatment for patients with aggressive connective tissue diseases. PMID- 1632664 TI - Isotype profile and clinical relevance of anticardiolipin antibodies in Sjogren's syndrome. AB - The purpose of this study was to determine the occurrence and clinical value of anticardiolipin antibodies in patients with Sjogren's syndrome. Thirty one patients with primary Sjogren's syndrome (all women, mean (SD) age 48.3 (11.2) years) and 32 patients with secondary Sjogren's syndrome with rheumatoid arthritis (all women, mean (SD) age 54.9 (11) years) were studied. IgG, IgM, and IgA anticardiolipin antibodies were determined by a standard enzyme linked immunosorbent assay (ELISA) technique. Anticardiolipin antibodies were found in five patients (16%) with primary Sjogren's syndrome and in seven patients (22%) with secondary Sjogren's syndrome. There was no correlation between anticardiolipin antibodies and the clinical features of the antiphospholipid syndrome (thrombotic events, fetal loss, thrombocytopenia) or extraglandular manifestations of Sjogren's syndrome (arthritis, skin lesions, myositis, polyneuropathy, central nervous system disease, pulmonary and renal disease) in either group. Among the various serological features studied, anticardiolipin antibodies correlated with antinuclear antibodies and antibodies to RNP only in patients with primary Sjogren's syndrome. These results indicate that although anticardiolipin antibodies are often found in serum samples from patients with Sjogren's syndrome, their clinical significance remains unclear. PMID- 1632665 TI - Effects of coagulation temperature on measurements of complement function in serum samples from patients with systemic lupus erythematosus. AB - Blood samples from 15 patients with systemic lupus erythematosus (SLE) and 15 healthy blood donors were allowed to coagulate for one hour at room temperature, followed by one hour at 4 or 37 degrees C. The complement activity of the serum samples was assessed by three different functional assays. Serum samples from patients with SLE obtained by coagulation at 37 degrees C had a lower complement activity than serum samples from blood coagulated at 4 degrees C when the capacity of the serum samples to solubilise precipitable immune complexes and to support the attachment of complement factors to solid phase immune complexes was determined. Haemolytic complement activity was not affected by the coagulation temperature. The content of C1q binding immune complexes in paired serum samples obtained after coagulation at 4 and 37 degrees C was similar and the size distribution of the immune complexes, determined by high performance gel permeation chromatography, was also similar. This study shows that the results of functional complement assays, applied to serum samples from patients with SLE cannot be compared unless the conditions for blood coagulation and serum handling are defined and are the same. The data also indicate that assays measuring complement mediated solubilisation of immune complexes and the fixation of complement factors to solid phase immune complexes are more sensitive indicators of complement activity than the haemolytic assay. PMID- 1632666 TI - Gait analysis in ankylosing spondylitis. AB - A study was conducted to compare the gait pattern of 12 patients with ankylosing spondylitis with axial disease only with that of 11 healthy controls using a telemeterised electrogoniometer gait analysis system. The reproducibility of the gait variables was found to be acceptable. Angles for movement at the hip and knee were less in patients with ankylosing spondylitis, but hip/knee angle ratios did not differ between the two groups. The stride length was shorter in the patients with ankylosing spondylitis. These findings are due to the increased rigidity of the spine, which results in decreased shock absorption and consequently a more cautious gait pattern in the absence of clinically and radiologically detectable peripheral joint disease. PMID- 1632668 TI - Infectious discitis caused by Enterobacter cloacae. AB - The case is reported of a patient who developed a vertebral osteomyelitis caused by Enterobacter cloacae. The organism was isolated in cultures of blood and vertebral puncture biopsy samples. The patient was satisfactorily treated with trimethroprim and sulphamethoxazole. Enterobacter cloacae, a Gram negative organism, has been confirmed as the cause of bacteremia in patients with burns, urinary infections, in adults with pneumonia, and in children with joint infections. Spondylodiscitis caused by Enterobacter cloacae has not previously been described. PMID- 1632667 TI - Giant cell arteritis of the female genital tract with temporal arteritis. AB - The clinical and pathological features of a patient with giant cell arteritis of the uterus and ovaries are described. A 61 year old woman had fever and weight loss over a period of eight months. A hysterectomy with bilateral salpingo oophorectomy was performed for a large cystic ovarian mass. Histological examination showed a benign ovarian cyst and unexpected giant cell arteritis affecting numerous small to medium sized arteries in the ovaries and myometrium. The diagnosis of temporal arteritis was confirmed by a random temporal artery biopsy, despite the absence of symptoms of temporal arteritis. This observation is compared with previously reported cases and the relation between granulomatous arteritis of the genital tract and temporal arteritis is discussed. The main differential diagnosis in this localisation was represented by Wegener's granulomatosis and periarteritis nodosa. PMID- 1632669 TI - Digital vasculitis after splenectomy in a patient with Felty's syndrome. AB - The case is reported of a man with Felty's syndrome in whom digital cutaneous vasculitis developed after a splenectomy. This may be a coincidental occurrence but a possible mechanism is suggested by which the splenectomy may have modified the immunopathology of the disease. PMID- 1632670 TI - Salvage of the infected arthroplasty. PMID- 1632671 TI - Health of the nation and osteoporosis. PMID- 1632672 TI - Adhesion of peripheral blood lymphocytes to high endothelial venules of gut mucosa. PMID- 1632673 TI - Potential for drug interactions in elderly patients with arthritis. PMID- 1632674 TI - Bronchiolitis obliterans in systemic lupus erythematosus. PMID- 1632675 TI - Pamidronate associated hallucinations. PMID- 1632676 TI - The 103rd Annual Scientific Session of the Southern Surgical Association. Hot Springs, Virginia, December 1-4, 1991. PMID- 1632677 TI - Prostaglandin E2 production during hepatic regeneration downregulates Kupffer cell IL-6 production. AB - The liver possesses the remarkable ability to regenerate to its original size after a 70% partial hepatectomy. There has been little effort to characterize the Kupffer cells' role in this unique mammalian reparative physiologic phenomenon. The capacity of rat Kupffer cells (KC) isolated at specific intervals after partial hepatectomy to produce interleukin-6 (IL-6) and prostaglandin E2 (PGE2) in response to endotoxin was evaluated in standard RPMI-1640 (1200 microM L arginine) and arginine-depleted RPMI-1640 (10 microM L-arginine) media. Regenerating liver KC 48 to 120 hours after partial hepatectomy responded to endotoxin stimulation with a significantly greater (p less than 0.05) production of IL-6 in standard RPMI-1640. Because Kupffer cells function in an environment where high arginase activity results in negligible L-arginine levels, the 10 microM L-arginine RPMI-1640 was used to simulate the true hepatic microenvironment. Production of IL-6 by regenerating liver KC was further increased (p less than 0.05) by placing these same KC in 10 microM L-arginine RPMI-1640 tissue culture media. During the same period, regenerating liver KC produced significantly (p less than 0.01) more PGE2 than sham-operated KC in both standard and low-arginine media. When the cyclo-oxygenase inhibitor indomethacin (1 x 10(-5) M) was added to cultures, the PGE2 production was inhibited, and IL-6 production was upregulated (p less than 0.05) in arginine-depleted cultures. The authors conclude that during hepatic regeneration KC IL-6 production is elevated but controlled in an autoregulatory fashion by KC PGE2 production. PMID- 1632678 TI - Percutaneous catheter drainage compared with internal drainage in the management of pancreatic pseudocyst. AB - The records of 92 patients with symptomatic pancreatic pseudocysts referred for surgical management over a 27-year period were retrospectively reviewed to compare outcome in 42 patients managed with operative internal drainage procedures (group I) with that in 52 patients managed with computed tomography directed percutaneous catheter drainage (PCD) (group II). The two groups were similar for patient age, sex, pseudocyst location, and cause. The frequency of antecedent pseudocyst-associated complications was less in group I (16.7 versus 38.5%, p less than 0.05). Seven group I patients and four group II patients had major complications (16.7 versus 7.7%, not significant). Group II mean duration of catheter drainage was 42.1 days, and the drain track infection rate was 48.1%. The frequency of antecedent operative cyst drainage was similar (14.2 versus 13.5%), as was the frequency of subsequent operations for complications related to chronic pancreatitis (9.5 versus 19.2%, not significant). Mortality rate was greater in group I (7.1% versus 0%, p less than 0.05). Pseudocysts can be effectively managed either by open operation with internal drainage or by PCD. Drawbacks of PCD include the controlled external pancreatic fistula and the risk of drain track infection. Percutaneous catheter drainage has the following advantages: (1) low mortality rate, (2) does not require a major operation, (3) does not violate the operative field in cases when subsequent retrograde duct drainage procedures are required. Neither PCD nor internal drainage is definitive, and with either technique subsequent correction of underlying pancreatic pathology may be necessary. PMID- 1632679 TI - The use of UW solution in clinical transplantation. A 4-year experience. AB - The development of the University of Wisconsin (UW) cold storage solution has extended safe preservation of the liver and pancreas from 6 to 24 hours or more. From May 1987 until November 1991, 288 livers and 163 simultaneous pancreas/kidney transplants were performed using UW solution. The mean preservation times were: liver, 12.7 +/- 4.4 hours, pancreas 17.2 +/- 4.4 hours, and kidney, 19.2 +/- 4.3 hours. Included in this series were 35 reduced-sized liver transplants, 7 cluster transplants, and 132 combined liver/pancreas retrievals. No differences in allograft function or graft-related complications were seen in organs preserved for less than or longer than 12 hours or in grafts from combined liver/pancreas retrievals. All pancreas/kidney transplants and most liver transplants were performed semi-electively. Actuarial 1-month patient and graft survival after liver transplantation was 91.4% and 80.2%, and at 4 years was 74.0% and 62.0%, respectively. After pancreas/kidney transplantation, the actuarial patient survival at 1 month and 4 years was 99.4% and 90.5%, respectively, whereas pancreatic and renal allograft survival at 1 month was 97.5% and 96.8%, and at 4 years was 83.0% and 83.4%, respectively. The ability to extend preservation times with UW solution has many advantages; however, the most important contribution of UW solution to clinical transplantation has been the increased utilization of scarce donor organs for more recipients because the previously imposed constraints on preservation time have been removed. PMID- 1632680 TI - Pancreas transplantation. An initial experience with systemic and portal drainage of pancreatic allografts. AB - Pancreas transplantation has evolved dramatically since its introduction in 1966. As new centers for transplantation have developed, the evaluation of complications associated with pancreas transplantation has led to advances in surgical technique. Furthermore, surgical alterations of the pancreas resulting from transplantation (systemic release of insulin and denervation) are of unproven consequence on glucose metabolism. Since 1988, the authors have performed 21 transplants (16 combined pancreas/kidney, 3 pancreas alone, which includes 1 retransplantation, 1 pancreas after previous kidney transplant, and 1 "cluster") in 20 patients aged 18 to 49 years; mean, 35 +/- 1 years. Overall patient survival is 95%. Three pancreatic grafts failed within the first year because of technical failure; one additional pancreas was lost to an immunologic event on postoperative day 449, for an overall pancreatic graft survival of 81%. No renal grafts were lost. To evaluate causes of graft failure, demographic data were compared, which included age and sex of the donor and the recipient, operative time, intraoperative blood transfusion, and ischemic time of the graft. No statistically significant differences were found between groups except for ischemic time (11.7 +/- 6.4 hours for the technical success group versus 19.8 +/- 3.7 hours for the technical failure group; p less than 0.05 by unpaired Student's t test). Quadruple immunosuppression was used, which included prednisone, cyclosporine, azathioprine, and antilymphoblast globulin. A mean of 1.2 (range, 0 to 3) rejection episodes per patient occurred. Mean hospital stay was 24 +/- 11 days. Surgical and infectious complications were evaluated by comparing the technical success (TS) group (n = 17) with the technical failure (TF) group. Surgical complications in the TS group revealed a mean of 1.3 episodes per patient, whereas the TF group had 3.7 episodes per patient. The TS also had a reduced incidence of infectious complications compared with the TF (1.7 versus 4.3 episodes per patient). Cytomegalovirus was common in both groups, accounting for 11 infectious episodes, and occurred on a mean postoperative day of 38. Mean postoperative HbA1C levels dropped to 5 +/- 1% from 11 +/- 3%. The authors developed a new technique that incorporates portal drainage of the pancreatic venous effluent in three recipients. Preoperative metabolic studies disclosed a mean fasting glucose of 211 +/- 27 mg/dL and a mean stimulated glucose value of 434 +/- 41 mg/dL for all patients; the mean fasting insulin was 23 +/- 4 microU/mL.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1632681 TI - The interrelation between sclerosing cholangitis and ulcerative colitis in patients undergoing liver transplantation. AB - Thirty-six patients underwent orthotopic liver transplantation (OLT) for primary sclerosing cholangitis under cyclosporine, azathioprine, and steroid immunosuppression. Of these patients, 29 suffered from chronic ulcerative colitis. The purpose of this study is to determine (1) whether replacement of the diseased liver and the altered immunocompetence suppresses the manifestation of chronic ulcerative colitis, and (2) if active colonic disease alters allograft function. Thirty of 36 patients survived OLT. After OLT, seven of 14 patients with symptomatic colon disease at the time of transplantation continue to suffer from active chronic ulcerative colitis, and three of 13 who were asymptomatic developed clinically active disease. Intractable colonic disease was the indication for post-OLT proctocolectomy in three patients, and one refused an indicated colectomy. Despite the long duration of the disease, none developed colonic malignancy. Long-term graft assessment showed good hepatocyte synthetic function in patients suffering from either active or inactive disease. Liver alkaline phosphatase, however, was significantly higher in patients suffering from active colonic disease. Furthermore, the alkaline phosphatase in symptomatic patients was higher than that seen in a matched cohort undergoing OLT for chronic active hepatitis or primary biliary cirrhosis. These results suggest that (1) liver replacement and immunosuppression in patients suffering from sclerosing cholangitis and ulcerative colitis do not alter the course of the colon disease, and (2) active chronic ulcerative colitis does not adversely affect allograft function, although elevation of alkaline phosphatase may be the harbinger of recurrence over the long term. PMID- 1632682 TI - Benefits of quadruple immunosuppressive therapy in recipients of living related donor kidneys. A review of 855 operations. AB - Eight hundred fifty-five living related donor transplant recipients were analyzed according to 15 potential risk factors with regard to patient and graft survival according to immunosuppression. Group I, 1968 to 1983, (n = 440 patients) received azathioprine and prednisone; group II, 1984 to 1987, (n = 229 patients) received triple therapy--azathioprine, prednisone, and cyclosporine; and group III, 1988-1991, (n = 186 patients), quadruple therapy--azathioprine, prednisone, cyclosporine, and Minnesota antilymphocyte globulin. Three important risk factors included immunosuppression, tissue typing, and race. Groups II and III had improved allograft survival over group I (p = 0.03). Patients with two haplotype matches had similar survival in all three groups. Kidney survival in one haplotype-matched recipients improved in group II and was equal to that of the two-haplotype-matched patients in group III. Cyclosporine improved allograft survival in both races when combined with azathioprine and prednisone. Quadruple therapy improved early survival in one-haplotype black patients, even though long term results remained better in whites. Cyclosporine did not improve graft survival in two-haplotype recipients. The addition of cyclosporine and quadruple therapy did not increase morbidity and mortality rates. PMID- 1632683 TI - Efficacy of a single pretransplant donor-specific transfusion and cyclosporin A administered 24 to 48 hours before one-haplotype-mismatched living related donor kidney transplant. AB - During the 7-year period from March 1984 to June 1991, 86 haploidentical living related kidney recipients were entered into one of three donor-specific transfusion (DST) and cyclosporine treatment protocols: (1) Multiple pretransplant DSTs with cyclosporine begun after transplant, n = 34; (2) Multiple pretransplant DSTs with cyclosporine begun pretransplant, n = 31; and (3) a single DST 24 to 48 hours before transplant with intravenous cyclosporine initiated after the transfusion, n = 21. Triple immunosuppression (prednisone, azathioprine, and cyclosporine) was continued in all groups after transplant. The 1-year patient (97%, 97%, and 93%, p = not significant) and graft (91%, 90%, and 87%, p = not significant) survival were similar for the three groups. No differences were seen in the incidence of rejection at 1 year (61%, 45%, and 60%, p = not significant) or in the incidence of infectious complications (26%, 42%, and 47%, p = not significant). It is concluded that a single DST given 24 to 48 hours before operation followed by pretransplant cyclosporine is as effective as classic DST conditioning of recipients using either pretransplant or post transplant cyclosporine. The single DST protocol has the advantage of not eliminating any donors because of sensitization and was less costly and easier to administer. PMID- 1632684 TI - Management of diabetic midfoot ulcers. AB - Diabetic midfoot ulcers are caused by bone and joint disruption that occur as a consequence of progressive peripheral neuropathy associated with this disease. This results in osseus deformities and areas of high pressure on the plantar surface of the midfoot, which cause the ulcers. These lesions are difficult to heal and frequently lead to amputation. In a series of 348 patients, 40 developed 54 midfoot ulcers. Limb preservation was achieved in 33 (61%). Wound closure was achieved in 32 (60%). The amputation rate was highest (83%) in the 10 of 12 patients with peripheral vascular disease. Successful therapy for limb preservation most often included an operation combining resection of underlying osseus deformities with debridement of affected soft tissues. PMID- 1632685 TI - Is type II diabetes mellitus (NIDDM) a surgical disease? AB - Since February 1, 1980, 515 morbidly obese patients have undergone the Greenville gastric bypass (GGB) operation. Of these, 212 (41.2%) were euglycemic, 288 (55.9%) were either diabetic or had glucose intolerance, and 15 (2.9%) were unable to complete the evaluation. After the operation, only 30 (5.8%) patients remained diabetic (and 20 of these improved), 457 (88.7%) became and have remained euglycemic, and inadequate data prevented classification of the other 28 (5.4%). The patients who failed to return to normal glucose values were older and their diabetes was of longer duration than those who did. The effect of the GGB was not only limited to the correction of abnormal glucose levels. The GGB also corrected the abnormal levels of fasting insulin and glycosylated hemoglobin in a cohort of 52 consecutive severely obese patients with non-insulin-dependent diabetes. The GGB effectively controls weight. If morbid obesity is defined as 100 pounds over ideal body weight, 89% of the patients are no longer "morbidly" obese within 2 years. In most patients, the control of the weight has been well maintained during the 11 years of follow-up; most of the upward creep in weight of 20.8% between 24 and 132 months was from the 49 (9.5%) patients who had staple line breakdowns between the large and small gastric pouches. Non-insulin dependent diabetes, previously considered a chronic unrelenting disease, can be controlled in the severely obese by the gastric bypass. Whether the correction of glucose metabolism affects the complications of diabetes is unknown. Whether the gastric bypass should be considered for patients with advanced non-insulin dependent diabetes but who are not severely obese deserves consideration. The GGB has an unacceptably high rate of staple line failure. Accordingly, the authors have recently changed their procedure to one that divides the stomach rather than partitions it with staples. PMID- 1632686 TI - The surgical management of infants and children with ambiguous genitalia. Lessons learned from 25 years. AB - Over a 25-year period, 91 children with ambiguous genitalia have received surgical management. Female sex assignment was made for 79. Of these, 60 patients underwent extensive clitoral reconstruction consonant with the female assignment. Forty-two patients had vaginal reconstruction. Factors relating to success include: (1) prompt and appropriate sex assignment; (2) early and accurate diagnosis; (3) conservative reconstruction of the clitoris at an early age (less than 1 year); and (4) choice of vaginal reconstruction based on the severity of the malformation. Long-term follow-up demonstrates satisfactory anatomic and functional results when clitoral surgery alone was required. Functional results for patients with extensive vaginal reconstruction have been compromised. Physicians caring for children with congenital intersexual anomalies can expect to encounter a wide spectrum of anatomic and physiologic derangements. Cosmetic appearance alone is an inadequate measure of success because endocrinologic, social, psychological, and sexual factors must be blended into comprehensive evaluation of these patients. The management plan must be flexible and individualized, incorporating long-term follow-up to adulthood. PMID- 1632687 TI - Nissen fundoplication in children with profound neurologic disability. High risks and unmet goals. AB - Anti-reflux procedures have been advocated in children with profound neurologic disability referred for feeding gastrostomy when gastroesophageal reflux is present. Facilitation of care, reduction in pneumonia and vomiting, and improvement in the general health and survival of these children have been major goals of fundoplication and gastrostomy. In large pediatric series, these procedures have been reported to have low risk and negligible mortality rates. Recent reports, however, document an increased incidence of sequelae of fundoplication in children with profound neurologic disability. This paper retrospectively reviews a series of 35 nonverbal, nonambulatory pediatric patients undergoing a total of 39 fundoplications (37 Nissen, 1 Thal, and 1 Belsey) over an 11-year period. Neurologic impairment of 17 (49%) patients was acquired, 13 (37%) congenital, and 5 (14%) due to a syndrome. Perioperative complications occurred in six (17%). Three additional complications led to early postoperative death. A fourth early death was unexplained. Fourteen (40%) had recurrent pneumonia, 11 (31%) recurrent vomiting, 8 (23%) choking-gagging retching complex, and 3 (9%) bowel obstruction requiring laparotomy. Recurrent gastroesophageal reflux was documented in seven (20%) patients. A second ARP was performed in six (17%). There were 14 (40%) late deaths. Although the major goals of anti-reflux procedure are clearly achieved in many severely impaired children with gastroesophageal reflux, the use of Nissen fundoplication to resolve the complications of swallowing disorders and improve outcome with an acceptably low risk in this complex set of patients does not appear to be established. PMID- 1632688 TI - Formal hepatic resection of colorectal liver metastases. Ploidy and prognosis. AB - Fifty consecutive patients who underwent 52 formal hepatic resections (excluding isolated wedge resections) for metastatic colorectal cancer were analyzed to determine whether DNA content was of prognostic significance. The Dukes' stages of the colorectal primaries were: A (10%), B (20%), C (40%), D (28%), and unknown in 2%. Four patients whose liver metastases were discovered at the time of resection of the primary bowel cancer underwent concomitant liver resection, and the remaining patients underwent delayed resections. The hepatic resections performed were right lobectomy (50%), extended right lobectomy (19%), left lobectomy (13%), left lateral segmentectomy (6%), left lobectomy and right wedge (6%), extended left lobectomy (4%), and right lobectomy and left wedge (2%). The overall morbidity rate was 29%. The in-hospital mortality rate was 9%. As of November 1991, 36 patients have recurred. The 5-year actuarial survival was 28%. Flow cytometry could be performed on 37 archival specimens, 15 of which were found to be diploid whereas 22 were aneuploid. All metastases from Dukes A colorectal primaries demonstrated a diploid DNA content. In addition, there was no difference in actuarial survival between diploid and aneuploid tumors. These data suggest that in selected patients, formal hepatic resection of colorectal liver metastases can be performed with an acceptable morbidity rate, mortality rate, and survival, but ploidy of the resected tumor is not of prognostic significance. PMID- 1632689 TI - Composite resection of posterior pelvic malignancy. AB - Advanced pelvic cancer is a formidable challenge to surgical resection. These tumors commonly invade the bony pelvis, may involve other viscera, and usually have been irradiated previously. The authors are presenting experience with 76 patients who had composite resection of posterior or lateral pelvic malignancy. Fifty-eight patients had secondary cancers involving the musculoskeletal pelvis. This included 47 patients with advanced carcinoma of the rectum (41 curative, 6 palliative), 10 epidermoid cancers of the anorectum (8) or cervix (2), and 1 bladder cancer. Among the 18 patients with primary pelvic tumors were three patients with chordomas, six with bone tumors (osteosarcoma chondrosarcoma, grade III giant cell tumor), and nine with soft tissue tumors. All required major resection of the sacrum or pelvic side walls, and one half had an additional exenterative procedure. The overall mortality rate was 7.9%. Long-term estimated survival was 24% in patients having curative resection of recurrent rectal cancer, and 22.5% in 10 patients with advanced epidermoid cancer. Fifty per cent of patients with primary bone or soft tissue tumors survived from 13 to 88 months. Most patients had reasonable return of function, and were able to return to work or resume their normal previous lifestyle. PMID- 1632690 TI - Does preoperative radiation therapy enhance the probability of local control and survival in high-risk distal rectal cancer? AB - One hundred forty-eight patients were treated with preoperative radiation therapy and surgery for resectable rectal adenocarcinoma at the University of Florida between 1975 and 1986. All patients had at least 5 years' follow-up; no patient was lost to follow-up. Three treatment protocols were used over the study period: 1975 to 1978, 3500 cGy in 20 fractions; 1979 to 1983, 4000 to 5000 cGy at 180 cGy per fraction; and 1984 to 1986, 3000 cGy in 10 fractions. The change was made to 3000 cGy in 10 fractions to reduce the inconvenience and expense associated with preoperative radiation therapy without sacrificing any improvement in local control or complication rates. There were no significant differences in the rates of local control, absolute survival, cause-specific survival, or complications between the three preoperative radiation therapy protocols. The results were compared for the 132 patients who underwent complete resection after preoperative radiation therapy and a series of 135 patients who underwent a complete resection alone for adenocarcinoma of the rectum at the University of Florida between 1959 and 1976. The results at 5 years, calculated by the product-limit method, for preoperative radiation therapy and surgery compared with surgery alone, respectively, were as follows: for local recurrence-free survival, 96% and 67%; for absolute survival, 66% and 40%; and for cause-specific survival, 77% and 50%. All of these differences are significant (p = 0.0001 or less). A subset of 56 patients with locally advanced lesions, based on tethering or circumferential involvement of the rectal lumen, treated with preoperative radiation therapy and surgery were compared with patients treated with surgery alone for stage B2 and C cancers. There was a significant improvement in local control and survival rates in the group irradiated before operation. There was no apparent increase in the incidence of postoperative complications in the patients irradiated before operation. PMID- 1632691 TI - Endovascular surgery. PMID- 1632692 TI - Acute appendicitis following blunt abdominal trauma. PMID- 1632694 TI - Routine choledochotomy with cholecystectomy. PMID- 1632693 TI - Acute appendicitis following blunt abdominal trauma: incidence or coincidence. PMID- 1632695 TI - Choledocholithiasis, endoscopic sphincterotomy or common bile duct exploration. PMID- 1632697 TI - Restrictions suggested, or enacted for residency training programs. PMID- 1632696 TI - Use of Swan-Ganz catheter to reduce morbidity and mortality rates after lower extremity revascularization procedures. PMID- 1632698 TI - Importance of adequate staging and of hormone receptors in women older than age 70 with breast cancer. AB - This report includes 479 women older than 70 years of age who were operated on between January 1980 and January 1988 and who were followed for 2.5 to 10.5 years (mean, 4.6 years). There were no operative deaths. Staging was available on 90.8%. Eighty-one per cent of patients were estrogen receptor positive (ER+), and 64% had negative lymph nodes (LN-). There were 50 deaths from breast cancer (10.4%), and 56 (11.6%) from other causes (mostly cardiovascular). Estrogen receptor negativity was significant by both univariate and multivariate analysis for increased risk of death from breast cancer (by factors of 3 and 1.4). Only four of 152 (2.6%) women who were node negative and estrogen receptor positive died during the follow-up of 4.9 years. The results of this study suggest that elderly women should be fully staged with axillary node dissections, and the hormone receptor assay should be performed because these are important indicators of prognosis. Because only 2.6% of the LN- and ER+ women in this study died of breast cancer, and only 3% in this group were treated with adjuvant systemic therapy (tamoxifen), the authors conclude that this therapy is unnecessary, although a prospective randomized study of elderly women would be required to state this definitively. PMID- 1632699 TI - The application of positron emission tomographic imaging with fluorodeoxyglucose to the evaluation of breast disease. AB - Positron emission tomography (PET) is a computer-aided tomographic imaging technique that uses positron-emitting compounds to trace biochemical processes of tissue, and construct images based on them. The authors applied a whole-body PET imaging technique to patients with breast masses or mammographic abnormalities using the isotope 2-[F-18]-fluoro-2-deoxy-D-glucose (FDG), in a clinical trial to evaluate the feasibility of using PET to identify primary breast cancer, axillary lymph node involvement, and systemic metastases, before surgical resection. Fourteen patients have been entered on this study, 10 of whom proved to have breast cancer. Positron emission tomography correctly predicted the nature of 12 of the 14 primary breast lesions, and correctly determined the lymph node status of 11 of the 14 patients. The authors conclude that PET with FDG has potential as a diagnostic modality for detection of primary breast cancer, particularly in the patient with radiodense breasts by conventional mammography, and that it has potential for the preoperative identification of axillary lymph node metastases. PMID- 1632700 TI - Complications of gastroesophageal reflux disease. Role of the lower esophageal sphincter, esophageal acid and acid/alkaline exposure, and duodenogastric reflux. AB - The factors contributing to the development of esophageal mucosal injury in gastroesophageal reflux disease (GERD) are unclear. The lower esophageal sphincter, esophageal acid and acid/alkaline exposure, and the presence of excessive duodenogastric reflux (DGR) was evaluated in 205 consecutive patients with GERD and various degrees of mucosal injury (no mucosal injury, n = 92; esophagitis, n = 66; stricture, n = 19; Barrett's esophagus, n = 28). Manometry and 24-hour esophageal pH monitoring showed that the prevalence and severity of esophageal mucosal injury was higher in patients with a mechanically defective lower esophageal sphincter (p less than 0.01) or increased esophageal acid/alkaline exposure (p less than 0.01) as compared with those with a normal sphincter or only increased esophageal acid exposure. Complications of GERD were particularly frequent and severe in patients who had a combination of a defective sphincter and increased esophageal acid/alkaline exposure (p less than 0.01). Combined esophageal and gastric pH monitoring showed that esophageal alkaline exposure was increased only in GERD patients with DGR (p less than 0.05) and that DGR was more frequent in GERD patients with a stricture or Barrett's esophagus. A mechanically defective lower esophageal sphincter and reflux of acid gastric juice contaminated with duodenal contents therefore appear to be the most important determinants for the development of mucosal injury in GERD. This explains why some patients fail medical therapy and supports the surgical reconstruction of the defective sphincter as the most effective therapy. PMID- 1632701 TI - A comprehensive multi-institutional study on postoperative adjuvant immunotherapy with oral streptococcal preparation OK-432 for patients after gastric cancer surgery. Kyoto Research Group for Digestive Organ Surgery. AB - The current study was designed to compare the effects of oral administration of the streptococcal preparation, OK-432, as an adjuvant immunotherapy versus those of intradermal administration of OK-432 on the survival of patients after surgery for gastric cancer. The patients were stratified into two groups after surgery: a curative surgery stratum and a palliative surgery stratum. Then the patients in each stratum were randomly assigned into three groups: an oral placebo group, an oral OK-432 group, and an intradermal OK-432 group. All of the patients were given fluoropyrimidines orally in combination with OK-432 or placebo for 2 years after surgery. A total of 1011 patients were registered between 1982 and 1985, and 970 patients were eligible for statistical analysis. The survival rate of the oral OK-432 group was significantly higher than those of the other two groups after curative surgery. There were no significant difference in the survival rates between the three groups after palliative surgery, however. The effect of oral OK-432 was quite pronounced in patients after curative surgery for stage II to IV gastric cancer, especially in those patients with regional node involvement. Furthermore, it was found that the spleen is necessary for effective immunotherapy with oral OK-432, because the survival rate of the oral OK-432 group was significantly improved in patients whose spleens were preserved, when compared with splenectomized patients. These results demonstrate that oral adjuvant immunotherapy with OK-432 is beneficial after curative surgery for gastric cancer. PMID- 1632702 TI - Prognostic value of CA 19.9 levels in colorectal cancer. AB - Pretreatment serum levels of carbohydrate antigen 19.9 (CA 19.9) and carcinoembryonic antigen were measured in 293 patients with colorectal cancer. Carbohydrate antigen 19.9 was above the cut-off limit of 37 U/mL in 35% of patients. Carbohydrate antigen 19.9 sensitivity was related to tumor stage. Carcinoembryonic antigen was above the cut-off level of 3.5 ng/mL in 61% of patients, and the simultaneous use of two markers increased sensitivity to 66%. The main use of pretreatment levels of CA 19.9 in locoregional cancer is in prognosis. Carbohydrate antigen 19.9 provided more prognostic information than that obtained by conventional staging methods. In patients with Dukes' C tumors, additional information was obtained for allocation of these patients into groups at low or high risk of recurrence. Prognostic significance of carcinoembryonic antigen was not independent of Dukes' classification. PMID- 1632703 TI - Continuous dual oximetry in surgical critical care. Indications and limitations. AB - Continuous dual oximetry combines pulse and venous oximetry to provide real-time information about oxygen utilization and pulmonary function. The authors undertook this study to examine the accuracy, utility, and limitations of the technique in surgical critical care. Twelve critically ill patients underwent placement of a modified pulmonary artery catheter and a pulse oximeter, both connected to an on-line computer. Paired blood gas and oximeter measurements were recorded every 4 to 6 hours, with a minimum of six sets per patient. Blood-gas derived shunt fraction correlated well with oximeter-derived ventilation perfusion index (r = 0.78, p less than 0.01). Further, the continuous oxygen extraction ratio (O2EI) and mixed venous oxygen saturation (SpvO2) correlated with the oxygen utilization coefficient (O2EI:r = 0.6, p less than 0.01; SpvO2, r = 0.76, p less than 0.01). Computer modeling of ventilation-perfusion index found limitations in accuracy that occur at high arterial oxygen saturations and when pulse oximetry errors are present. The authors conclude that (1) Continuous dual oximetry offers a significant advantage over routine blood gas analysis for monitoring cardiopulmonary parameters in critically ill patients because of its real-time display; (2) Oximeter-derived determinations parallel traditional parameters; and (3) The most significant technical limitations occur primarily at high arterial saturations and with pulse oximetry errors. PMID- 1632704 TI - Body composition and surgical treatment of obesity. Effects of weight loss on fluid distribution. AB - Obesity is associated with absolute and relative expansion of the extracellular water compartment (ECW). The effects of substantial and prolonged weight reduction on body water distribution are unknown, however. The authors studied total body water (TBW) by tritiated water dilution, ECW by 35SO4 dilution, exchangeable sodium (Na(e)) by 24Na, and total body potassium (TBK) by 40K whole body counting in 25 severely obese women (body mass index [BMI] = 48 +/- 7 kg.m 2, mean +/- standard deviation) aged 36 +/- 8 years before and at intervals after gastric restrictive (GR; n = 12) and malabsorptive (MA; n = 13) operations for obesity. Results are compared with a control group of 26 healthy normal-weight women (BMI = 21 +/- 2). Before operation, the obese patients had absolute elevations of all water compartments compared with controls, with significantly higher ratios of Na(e) to TBK (1.17 +/- 0.13 versus 0.91 +/- 0.10; p less than 0.05) and ECW to intracellular water (ICW) (E/I = 0.82 +/- 0.17 versus 0.63 +/- 0.06; p less than 0.05). After weight loss of 52 +/- 20 kg in MA and 47 +/- 19 kg in GR patients (nonsignificant between groups) to a stable level 22 +/- 8 months after operation, there were statistically significant reductions in TBW, ICW, TBK, and Na(e) in both groups, but a significant reduction in ECW only after GR. Adjusting for preoperative weight, duration of follow-up, and rate of weight loss, E/I was greater after MA than GR (1.09 +/- 0.25 versus 0.82 +/- 0.14; p less than 0.05). The elevated preoperative E/I ratio did not normalize with weight loss after surgery, and the response was related to the type of operation. The finding remains to be explained although the increased E/I after MA may reflect mild protein-calorie malnutrition not detectable in the blood. The persistence of elevated E/I with significant weight loss after GR might imply an intrinsic or irreversible imbalance of fluid distribution in obese patients. PMID- 1632705 TI - Infrainguinal anastomotic arterial graft infections treated by selective graft preservation. AB - The purpose of this study was to determine whether the type of graft material and bacteria involved in an infrainguinal arterial anastomotic infection can be used as guidelines for graft preservation. Between 1972 and 1990, the authors treated 35 anastomotic infections involving a common femoral or distal artery. The graft material was Dacron in 14 patients, polytetrafluoroethylene (PTFE) in 14, and vein in 7. Of the 14 Dacron grafts, immediate graft excision was required for overwhelming infection in eight patients (bleeding in five, sepsis in three) and for an occluded graft in one patient. Three of five patients failed attempted graft preservation because of nonhealing wounds. Thus, 12 of the 14 Dacron grafts ultimately required graft excision. Of the 21 "smooth-walled" vein and PTFE grafts, 10 required immediate graft excision for occluded grafts (five PTFE, one vein) or bleeding (three PTFE, one vein). Ten of the remaining 11 (91%) patients with patent "smooth-walled" grafts, intact anastomoses, and absence of sepsis managed by graft preservation healed their wounds and maintained distal arterial perfusion. Wound cultures grew pure gram-positive cocci in 17 of 21 "smooth walled" graft infections versus 8 of 14 Dacron graft infections. In the absence of systemic sepsis, graft preservation is the treatment of choice for gram positive infections involving an intact anastomosis of patent PTFE and vein grafts. Regardless of the bacterial cause, the authors recommend that any infrainguinal anastomotic infection of a Dacron graft be treated by immediate excision of all infected graft material. PMID- 1632706 TI - Carl John Wiggers' visionary views on vivisection. PMID- 1632707 TI - Dr. Halsted's secret operation on Dr. Matas. PMID- 1632708 TI - Clinical variables associated with high risk of associated abdominal injury. PMID- 1632709 TI - Adverse effect of therapeutic vasoconstrictors in experimental acute pancreatitis. PMID- 1632710 TI - [The implantable defibrillator-cardioverter in the treatment of malignant ventricular arrhythmias]. PMID- 1632711 TI - [Bilateral infundibula in congenital cardiopathies]. AB - The goal of this paper has been to count and describe congenital heart disease associated with double conus. We studied 196 pathologic specimens from to the Pathologic Collection of the Department of Embryology of the National Institute of Cardiology "Ignacio Chavez" of Mexico. We found 3% of double conus in classic tricuspid atresia with concordant ventriculoarterial connection, 53% with double outlet right ventricle, 16% with discordant ventriculoarterial connection, 91% with double outlet single ventricle, 8% with one outlet right ventricle with pulmonary atresia, 20% with one outlet left ventricle and 25% with one outlet single ventricle. The morphological data of the associated anomalies were gathered in an informatized sheet designed according the segmental and sequential approach to diagnose congenital heart disease. From our results we conclude that double conus cannot be considered pathognomonic of any congenital cardiopathy, although they appear associated more frequently with truncoconal anomalies and single ventricle. It is frequent the association between double conus and stenosis of one of them, specially the subpulmonary one. We found great association between left juxtaposition of the atrial appendages and double conus. PMID- 1632712 TI - [The clinical and electrophysiological characteristics of patients with idiopathic ventricular tachycardia]. AB - Clinical and electrophysiological characteristics in 20 patients with clinical ventricular tachycardia and normal hearts documented by physical examination, echocardiography, and angiocardiography were analysed. There were 11 males and 9 females. All patients had sustained ventricular tachycardia without hemodynamic instability during tachycardia. A right bundle branch block morphology of ventricular tachycardia was present in 14 patients and left bundle branch block morphology in six patients. During electrophysiologic studies, ventricular tachycardia was induced in 10/15 (66%) patients. Intravenous verapamil terminated the ventricular tachycardia in 9/10 (90%) of cases. However oral verapamil not prevented recurrences. Among 14 patients on whom exercise tests were performed, only two had exercise-induced ventricular/tachycardia. Late potentials were positive in 3/14 (21%) cases and one patient died suddenly during exercise without antiarrhythmic drugs. PMID- 1632714 TI - [The usefulness of transesophageal echocardiography during percutaneous balloon mitral valvulotomy]. AB - The purpose of this study is to report the experience at Instituto de Cardiologia de Mexico with transesophageal echocardiography during percutaneous mitral valvulotomy and to compare its utility with transthoracic echocardiography. Sixteen patients with isolated or predominant mitral stenosis were examined and underwent percutaneous mitral valvulotomy with a single balloon catheter (Inoue [correction of Ionue] technique). Transthoracic echocardiography was done in all cases previous to the procedure. The procedure orientation was done with transesophageal in thirteen patients and with. Transthoracic echocardiography in the other three. The results were successful in all cases. Transesophageal echocardiography was more useful in the initial evaluation in patients with poor transthoracic windows, in those with clinical and/or transthoracic evidence of atrial thrombosis, as well as in procedure orientation, spontaneous contrast detection, mitral regurgitation and atrial septal defect evaluation after the procedure. Transesophageal echocardiography is superior to transthoracic technique in procedure orientation, early evaluation of results and potential complications. However, its practical utility is limited and its routine use is not recommended. PMID- 1632713 TI - [Atrioventricular and ventriculoatrial conduction in patients operated on for the Wolff-Parkinson-White syndrome]. AB - Over the last decade the surgical treatment of the Wolff-Parkinson-White syndrome has been well accepted. It is important to make an early diagnosis for surgical success. For this purpose we utilized programmed electrical stimulation to assess the functional characteristics of atrioventricular and ventriculoatrial conduction in our post-operative patients. In 55% of the cases we found accelerated nodal conduction. Programmed electrical stimulation correctly identified 90% of successfully treated patients. We did not found any false positive curve, therefore, this method has a high specificity. We concluded that in post-operative patients with the Wolff-Parkinson-White syndrome: 1- There is a high incidence of accelerated nodal conduction and 2- programmed electrical stimulation can correctly identify most of the patients who were successfully treated. PMID- 1632715 TI - [An electro- and vectorcardiographic study of ventricular activation in scleroderma]. AB - Electrical ventricular activation was studied by means of electrocardiogram and vectorcardiogram in 62 patients, 55 women and 7 men, affected by systemic sclerosis of average disease duration of 10.3 years. 45% of the patients showed the "diffused form" of the disease and 55% the "limited form". The vectorcardiogram showed some alterations of the ventricular activation in 55% of the recorded cases. The previous electrocardiogram found only 18%. The alterations, which are more frequent in the diffuse form than in the limited one, are the presence of loss of forces in septal, lateral or inferior or combined areas and intraventricular conduction disorders as complete and incomplete right bundle branch block, left anterior subdivision block, left posterior subdivision block, or combination between incomplete right bundle branch block and left anterior or posterior subdivision block. The vectorcardiogram was more sensitive than the electrocardiogram in showing loss of forces, also in patients with the limited form of systemic sclerosis, when the electrocardiogram was normal. Moreover the vectorcardiogram is helpful to identify left posterior subdivision block. The vectorcardiographic investigation seems to be a useful complement of the electrocardiogram especially for the identification of cases with myocardial involvement that is clinically silent. PMID- 1632716 TI - [An assessment of myocardial ischemia in women with the exercise test validated by coronary angiography]. AB - Ischemic heart disease has been studied in men and women only as a group. We studied the sensitivity and specificity of the exercise stress testing in women. The exercise stress testing (EST) was validated with the coronary arteriography. We studied 72 women and 129 men, the mean age was 55 years for women and 51 years for men. We found in women 83.2% of estimated maximal heart rate; the rate pressure product was 2.4, no different from the values recorded in men (p greater than 0.06). The blood pressure response to exercise was higher in women, and the maximal work capacity was more elevated in men (p less than 0.006). We found normal coronary arteries in 41 women, 70.7% with a positive (EST) compared with a 87.07% in men. The sensitivity and specificity of the exercise stress testing for the diagnosis of ischemic heart disease is smaller in women. PMID- 1632717 TI - [Premature atherosclerosis in a 17-year-old male with diabetes mellitus and familial dyslipoproteinemia]. AB - A 17-year-old male was admitted with an acute myocardial infarction. A coronarography showed 90% occlusion in of the descendent anterior artery. A coronary angioplasty was done with excellent response. As coronary risk factors he had diabetes mellitus for 5 years and dyslipidemia with a phenotype IIb and hypo-alpha-lipoproteinemia. The case is discussed in regard to the possible etiopathogenic causes for his premature atherosclerosis. PMID- 1632718 TI - [The effects of captopril in stable angina pectoris]. AB - Eighteen normotensive patients with coronary disease and stable effort-induced angina were selected. The effect of captopril was studied. A Bruce stress test was obtained before and after administration of conventional treatment with captopril or placebo. The captopril induced less systolic pressure elevation during maximal exercise without modification of heart rate. By decreasing myocardial oxygen consumption, increasing the time in which angina appears during exercise. Captopril may prove to be useful adjunct to the antianginal drug regimens of patients with stable angina and systolic arterial pressure greater than 110 mm Hg. PMID- 1632719 TI - [The prevalence of hypertension and associated factors in a political district of Mexico City]. AB - A cross-sectional study was conducted in order to know the prevalence of hypertension and some characteristics related as age, sex, obesity, smoking, heredity and exercise, in a mexican population; their possible causal role is discussed. Other variables related with the treatment and control of hypertension were explored as the awareness of personal blood pressure figures and regularity of treatment among hypertensives. The global hypertension prevalence was 26.9% (CI 95% 24.0-29.0), male's prevalence was 33.7% (CI 95% 29.0-38.0) and female's prevalence was 24.3% (CI 95% 22.0-27.0). Age, sex, obesity and heredity were the most associated characteristics on systolic and diastolic mean figures. The Prevalence Odds Ratios (POR) were 1.79 (CI 95% 1.4, 2.29) for obesity; for smoking 1.41 (CI 95% 1.1, 1.82), heredity 1.23 (CI 95% 0.92, 1.64), and sport practice 0.95 (CI 95% 0.64, 1.39). Among population studied only 61.1% knew their habitual blood pressure figures, and among known hypertensives only 27.1% were on regular anti-hypertensive treatment. PMID- 1632720 TI - [Intraesophageal electrocardiography: an old technic under a new concept]. AB - Transesophageal recording of heart potentials is a fully accepted procedure for the electrical study of the heart. However, the intraesophageal ECG could be explored even better by using multipolar catheter electrodes and by considering various characteristics of the tracing such as amplitude, frequency and velocity. The authors describe their experience with the use of these electrodes and recording characteristics applied to the field of investigation and diagnosis of the electrical activity of supraventricular region. This objective can also by achieved by constructing esophagus-thoracic wall bipolar derivations. PMID- 1632721 TI - Homotopic transplant of fetal cortex to lesioned motor cortex of adult rats. A comportamental and anatomical study. AB - Previous investigations have shown that the transplant of fetal nervous tissue in adult, formerly injured, brain induces an improvement of the neurological deficits. The process underlying this finding is not yet known. It has been proposed that this process is favourably supported by the reconstruction of the damaged circuitry, replacing the injured neurons with the transplanted fetal cells. In the present study we have investigated the relation between the improvement of the neurological deficits and the anatomical integration of the transplanted neurons within the host brain. The plan of the investigation included two steps: the first step consisted of inducing neurological deficits by kainic acid lesion of the motor cortex and then studying the changes in the motor learning following a homotopic transplant of fetal cortex in the side of the lesion. The second step consisted of studying the anatomical integration of the transplanted cortex with the thalamus of the host. The results showed that the rats with injury of the motor cortex followed by solid transplant of fetal cortex (E 17) had a significantly greater recovery of the motor learning with respect to non-transplanted rats with a lesioned motor cortex. In the same rats, the connections between the transplanted cerebral cortex and the thalamus of the host has been investigated. WGA-HRP solution was injected in the thalamus and both labeled fiber terminals and labeled cells were searched for in the transplants. The results showed that: 1) the host thalamus projects to the transplanted cortex with a lower density than to the host cortex surrounding the transplant; 2) the thalamic projection to the host cortex is topographically organized, whereas the projection to the transplant is arranged in patches without any topographical organization; 3) the transplant does not send a significant projection to the thalamus of the host. In conclusion, the experimental findings demonstrate that the reconstruction of an injured thalamo-cortical circuitry of adult rats transplanting fetal neurons is not possible. The improvement of the functional deficits by the transplant of fetal tissue may be referred to aspecific factors enhancing the functional activity of the host cortex undamaged by the initial injury. The identification of the nature of the hypothesized factors requires further investigation. PMID- 1632722 TI - Neuronal mechanisms of interaction of Deiters nucleus with the cerebral cortex. AB - The effects of stimulation of the vestibular nerve and five different cerebral cortex areas on the neuronal activity of the lateral vestibular nucleus of Deiters were studied. Stimulation of the cerebral cortex is shown to lead to antidromic and synaptic activation of Deiters neurons. The synaptic potentials of Deiters neurons evoked from the cerebral cortex were of mono- and polysynaptic origin. In particular, stimulation of the cerebral cortex evoked in Deiters neurons mono- and polysynaptic excitatory postsynaptic potentials. Collaterals of vestibulospinal neurons reaching different cortex fields as well as convergence of influences from these cortex fields on Deiters neurons were revealed. Inhibitory effects of the cerebral cortex on Deiters neurons were of polysynaptic origin and occurred rarely. The topical correlation between Deiters nucleus and different areas of the cerebral cortex was found. The peculiarities and functional significance of the effects obtained are discussed. PMID- 1632724 TI - A comparison of the interferon gamma assay with the absorbed ELISA for the diagnosis of Johne's disease in cattle. AB - Two interferon gamma (IFN-gamma) assays, the IFN-gamma enzyme immunoassay (EIA) and the IFN-gamma bioassay and an absorbed ELISA were used to screen 6 cattle herds for Johne's disease. Each herd had a history of Johne's disease but the majority of infected animals did not show clinical signs. The disease status of the cattle, which were removed from the herds, was confirmed by bacteriological culture of faeces or histopathological examination and culture of tissues collected at necropsy. The sensitivities of the IFN-gamma assays and the absorbed ELISA were determined using test results from infected animals. The sensitivity of the IFN-gamma EIA in detecting subclinical (71.8 to 93.3%) and clinical animals (100%) was not significantly different. However, the IFN-gamma bioassay and the absorbed ELISA were more sensitive in detecting cattle with advanced infections (80%) than those that were subclinically affected (16.7 to 33.3%). PMID- 1632723 TI - Effects of microinjection of vasopressin in dorsal pontine reticular structures on the gain of vestibulospinal reflexes in decerebrate cats. AB - 1. The possibility that vasopressin (VP) acts on the dorsal pontine reticular formation (pRF) and the related medullary inhibitory reticulospinal (RS) system to control posture as well as the vestibulospinal reflexes has been investigated by injecting small doses of VP in precollicular decerebrate cats. 2. Unilateral microinjection of VP (0.25 microliters at the concentration of 10(-11) micrograms/microliters saline) in the pRF decreased the extensor rigidity in the ipsilateral limbs, while that of the contralateral limbs either decreased or increased. The same injection also produced a moderate or a prominent increase in gain of the multiunit EMG responses of the ipsilateral triceps brachii to roll tilt of the animal (t-test, P less than 0.001 for either group of responses). In the first instance the response gain of the contralateral triceps brachii to animal tilt slightly increased, while the pattern of response remained always of the alpha-type, as shown for the ipsilateral responses (increased EMG activity during ipsilateral tilt and decreased activity during contralateral tilt). In the second instance, however, the response gain showed only slight changes, while the pattern of responses reversed from the alpha- to the beta-type. These findings occurred 5-20 min after the injection, fully developed within 30-60 min and disappeared in about 2-3 hours. 3. The structures responsible for the postural and reflex changes described above were located in the dorsal pontine tegmental region immediately ventral to the LC, and included the peri-LC alpha and the surrounding dorsal pRF. The induced effects depended upon the injected neuropeptide, since previous injection of an equal volume of saline stained by the pontamine sky blue dye into the same dorsal pontine area was ineffective. 4. We postulated that VP exerts an excitatory influence on ipsilateral dorsal pRF neurons. The increased discharge of these neurons and the related medullary inhibitory RS neurons would lead to a decreased postural activity in the ipsilateral limbs. However, since these inhibitory RS neurons fire out of phase with respect to the excitatory vestibulospinal neurons, it appears that the higher the firing rate of the RS neurons in the animal at rest, the greater the disinhibition that affects the limb extensor motoneurons during ipsilateral tilt. These motoneurons would then respond more efficiently to the same excitatory volleys elicited by given parameters of stimulation, thus leading to an increased gain of the EMG responses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1632725 TI - Genetic diversity among Australian and New Zealand isolates of Leptospira interrogans serovar pomona. AB - Restriction endonuclease analysis of 16 Australian and 4 New Zealand isolates of Leptospira interrogans serovar pomona showed that they could be divided into 3 genetic groups. Most of the isolates closely resembled the serovar kennewicki reference strain, and they all differed from the reference strain of serovar pomona. Based on these findings, it is suggested that vaccine manufacturers re evaluate their choice of serovar pomona vaccine strain. PMID- 1632726 TI - The occurrence of Dirofilaria immitis in dogs in South Australia. AB - Heart, lung and samples of blood from 230 dogs were examined for infections of filarial parasites. Dirofilaria immitis worms and microfilariae were detected in one dog. Blood samples from a further 1428 dogs were examined for microfilariae and 22 were found to be infected. Eighteen dogs were infected with D immitis microfilariae and four with Dipetolonema reconditum microfilariae. The histories were available for 18 of the dogs infected with heartworm and only seven dogs had not travelled outside South Australia. It was concluded that heartworm infection was endemic in South Australia but the apparent prevalence was only about 1%. PMID- 1632727 TI - Myodegeneration in rats fed Melia azedarach. PMID- 1632728 TI - Further analysis of bile crystals from sheep grazing Panicum schinzii (sweet grass). PMID- 1632729 TI - The efficacy of synthetic pyrethroid insecticides applied to the backline of sheep against four strains of lice (Damalinia ovis). PMID- 1632730 TI - Acute interstitial pneumonia in cattle associated with consumption of mould damaged sweet potatoes (Ipomoea batatas). PMID- 1632731 TI - Bacterial inhibitory residues in pigs fed mouldy grain. PMID- 1632732 TI - A congenital haemolytic anaemia and jaundice of Murray Grey calves. PMID- 1632733 TI - Amyloidosis in an Angora goat. PMID- 1632734 TI - Confocal microscopy of the antigen-antibody reaction site in nematode larvae. PMID- 1632735 TI - Performance of Australian wethers in Arabian Gulf feedlots after transport by sea. PMID- 1632736 TI - Dirofilaria immitis in cats. PMID- 1632737 TI - The multiple, sclerotic form of osteogenic sarcoma. PMID- 1632738 TI - The post therapy breast. AB - Both systemic and local therapy, for conditions of the breast and unrelated to it, may produce mammographic changes. Some of these are characteristic, such as the pattern of scarring seen in reduction mammoplasty. In many other instances, however, the changes produced overlap features commonly seen in malignancy. A knowledge of the timing, natural history and spectrum of these changes will aid mammographic interpretation. PMID- 1632739 TI - CT demonstration of complex dorsal spinal dysraphism. AB - An unusual case of dorsal spinal dysraphism in a four year old child is presented. Various abnormalities including diastematomyelia, an extradural arachnoid cyst arising from one of the two dural tubes, and lipomeningomyelocele with a related rib-like bony structure were demonstrated with Iohexol CT and subsequently confirmed at surgery. PMID- 1632740 TI - Radiological imaging of urinary tract infection in Malaysian children--a private hospital experience. AB - The results of radiological investigations performed on 81 children with urinary tract infection (UTI) were reviewed. Investigations included 91 voiding cystourethrograms (VCU), 59 intravenous urograms (IVU) and 36 ultrasonograms (US). The aim was to study the local spectrum of renal tract abnormalities in childhood UTI and to compare the diagnostic yield of combining US and VCU against IVU and VCU. Renal tract abnormalities were detected in 37%. Vesico-ureteric reflux (VUR) was the commonest, detected in 26%, with renal scarring found in 9% of refluxing units. Ultrasound should replace IVU in the initial diagnostic work up of these children. PMID- 1632741 TI - Hydrocolpos in siblings--percutaneous management. PMID- 1632742 TI - Malignant mesothelioma of the tunica vaginalis testis. AB - A patient is described with an indolent scrotal mass complicated by acute hydrocoele which was proven to be due to malignant mesothelioma of the tunica vaginalis testis. Although uncommon, the possibility of scrotal mass lesion should be considered in ultrasound examination of hydrocoeles with atypical presentations. PMID- 1632743 TI - Computed tomography of the abdomen with fat density oral contrast medium. AB - A 12.5% corn oil-emulsion (COE) was tested as an oral contrast agent for abdominal computed tomography (CT) examinations in 100 patients. The results were compared with those obtained from another group of patients who received a conventional, high-density, oral contrast agent (2-3% iodinated solution). There was no statistically significant difference in the subjects' tolerance to the two agents (P greater than 0.05). There was, however, a significant improvement in image quality with COE (P less than 0.05). Gastrointestinal tract discrimination, and mucosal and mural visualisation was of higher quality with fat density oral contrast medium than with the high-density contrast agent. These data suggest that COE should be considered for routine use as an alternative to conventional high density oral contrast agents in upper abdominal CT. PMID- 1632744 TI - Primary hypothyroidism with pituitary enlargement and a visual field abnormality. AB - A 23 year old man presented with classical hypothyroidism of 9 years duration. This was associated with pituitary enlargement, documented on magnetic resonance imaging (MRI), and abnormal half-field visual evoked responses (VERs). Following the initiation of thyroxine therapy the pituitary enlargement and the VER abnormalities resolved. The final diagnosis was of primary hypothyroidism with secondary pituitary hyperplasia. PMID- 1632745 TI - CT findings in tuberculous spondylitis. AB - The computed tomographic (CT) features of ten documented cases of spinal tuberculosis were analyzed. All cases showed evidence of vertebral body destruction, with paravertebral soft tissue masses. Four cases revealed extension of involvement into the neural arches. Calcification within the paraspinal soft tissue was found in only two cases. Two of four cases who received intravenous contrast medium demonstrated evidence of rim enhancement around multilocuated fluid collections. Compared to conventional roentgenography, CT better delineated the extent of bony destruction, involvement of the spinal canal and existence of paraspinal soft tissue masses. PMID- 1632746 TI - Magnetic resonance imaging in carotid dissection. AB - Magnetic Resonance Imaging was performed in two cases of suspected internal carotid artery dissection. In both cases it was possible to demonstrate the dissection. It is suggested that magnetic resonance imaging (MRI) could replace more invasive techniques in the diagnosis of this condition. PMID- 1632747 TI - Co-axial needle for use with the Biopty Gun. PMID- 1632748 TI - Echographic, radiological and anatomo-pathological evaluation of a foetus with Neu-Laxova syndrome. PMID- 1632749 TI - Comparison of duplex ultrasound with angiography in assessment of carotid bifurcation disease. AB - This is a study comparing duplex ultrasound against the "gold standard" of angiography in assessing atherosclerotic disease of the carotid bifurcation, prior to prospective endarterectomy surgery. Thirty-nine patients were studied with both sonography and angiography studies being performed within one month of each other. Plaques were described by sonography as being "smooth" or "irregular" in surface and "homogeneous" or "heterogeneous" in composition. Ultrasound showed an overall 92% sensitivity, against the standard of angiography, in its ability to assess the degree of internal carotid stenosis. There was only a 63% sensitivity with the common carotid arteries and only a 65% sensitivity with the external carotid arteries. Ultrasound did not show a high accuracy in detecting plaque ulceration when compared against angio-graphy. PMID- 1632750 TI - Pulmonary artery pseudoaneurysm secondary to Swan-Ganz catheterization--a case report. PMID- 1632751 TI - Meckel syndrome: prenatal ultrasonographic diagnosis in two cases showing marked differences in phenotypic expression. AB - Two consecutive siblings with the Meckel-Gruber syndrome are presented. They demonstrate variation in phenotypic expression which may render diagnosis difficult when the pattern of malformation is significantly different from that traditionally accepted. The diagnosis was only made with confidence because a sibling with typical features had been seen first. The usefulness of ultrasound in prenatal diagnosis, even when the abnormalities are atypical, is well illustrated. PMID- 1632752 TI - Embolisation in the management of peripancreatic pseudoaneurysm--a case report. AB - Peripancreatic pseudoaneurysms are an unusual cause of haemorrhage in patients with chronic pancreatitis and pseudocysts. We describe a 28 year old alcoholic male with documented chronic pancreatic pseudocysts, who presented with melaena and a large pulsatile epigastric mass. Ultrasound and digital subtraction angiography revealed a pseudoaneurysm of the gastroduodenal artery. This was successfully embolised with stainless steel coils. Surgical intervention in such cases is associated with high mortality, and the role of embolisation as an initial therapy is well established. The role of embolisation as definitive therapy is less clear. PMID- 1632753 TI - Agenesis of the right lobe of the liver: diagnosis by computed tomography. AB - Agenesis of the right lobe of the liver is a rare congenital anomaly with characteristic features on computed tomography (CT). We present a case diagnosed as an incidental finding and describe the CT appearances. PMID- 1632754 TI - Mammographic microcalcification in axillary lymph nodes. PMID- 1632755 TI - CT in complete congenital eventration of diaphragm with aplasia of lung. AB - Complete eventration of the diaphragm and pulmonary aplasia, though rare anomalies, should be considered in new-borns with respiratory distress. Such anomalous conditions occurring either alone or in combination elude diagnosis and pose problems for management. CT is a very effective, non invasive means of diagnosis which in the past depended largely on invasive procedures such as bronchography, angiography and thoracotomy. PMID- 1632756 TI - Gastric dilatation and necrosis in bulimia: a case report. AB - Gastric dilatation and perforation is a rare complication in anorexia/bulimia sufferers. We describe a 24 year old female who presented with severe abdominal pain and vomiting, in whom radiographs demonstrated gross gastric dilatation and subsequent perforation. Although gastric perforation is rare, one can anticipate a rising incidence, with the apparent increase in the incidence of bulimia. PMID- 1632757 TI - Acute osteomyelitis: early diagnosis by ultrasonography. AB - A prospective study was carried out to evaluate the role of ultrasound in early detection of infections of bone. Presence of a hypoechoic collection adjacent to bone was considered highly suggestive of osteomyelitis whereas a hypoechoic collection away from the bone implied a soft tissue abscess. Cellulitis presented as increased subcutaneous thickness. Of the 31 patients clinically suspected to have osteomyelitis, and subjected to ultrasound, 25 were proven to be osteomyelitis at surgery or by subsequent radiological changes, 4 had soft tissue abscesses and the remaining 2 had cellulitis. Co-existent hip joint effusion was seen in 2 patients. It is felt that ultrasound is simple and non-invasive investigation, capable of detecting bone and soft tissue infections. PMID- 1632758 TI - Magnetic resonance imaging in occult spinal dysraphism. AB - A prospective study was carried out in 100 cases of suspected occult spinal dysraphic anomalies with Magnetic Resonance Imaging in order to determine its diagnostic efficacy as the initial imaging modality. MR imaging provided accurate preoperative information in 91 out of 92 cases (98.9%). Some of the unusual and interesting findings in the series were: presence of intrinsic cord abnormality in 19 out of 21 cases (90.4%) with a normal plain radiograph, 4 cases of diastematomyelia with a dermoid in the dorsal and lumbar region associated with syringohydromyelia, intradural fibrous/glial bands, syringohydromyelia/myelomalacia of the conus with tethered cord syndrome having a normally placed conus, and myelocystocele. It is concluded that MRI is an excellent primary diagnostic tool, together with a plain radiograph, for complete preoperative evaluation of mid-line spinal anomalies. PMID- 1632759 TI - Inadvertent duodenal stenting: a case report. AB - A Gianturco type metallic stent placed in the common bile duct migrated into the duodenum. The device remains in situ, and has caused no ill-effects to date. This raises the possibility that such stents may be deployed in the gastrointestinal tract. PMID- 1632760 TI - Editor's case quiz (1). Xanthogranulomatous pyelonephritis with bronchorenal fistula. PMID- 1632761 TI - Novel glycosylation-defective baby hamster kidney cells. AB - The plant lectin wheat germ agglutinin (WGA) has previously been used to select more than ten different glycosylation-defective phenotypes in a variety of mammalian somatic cells. Three WGA-resistant phenotypes have now been obtained spontaneously from baby hamster kidney (BHK) cells. These mutant BHK cells exhibit a pattern of cross resistance and sensitivity to multiple plant lectins, suggesting that the cell surface carbohydrates of these cells are altered. Two WGA-resistant BHK phenotypes appear similar to WGA-resistant CHO cells that lack terminal sialic acid and galactose residues on their cell surface carbohydrates. The third WGA-resistant BHK cell phenotype has not previously been seen in WGA resistant mammalian cells. PMID- 1632762 TI - Properties of 1-methyladenine receptors in starfish oocyte membranes: involvement of pertussis toxin-sensitive GTP-binding protein in the receptor-mediated signal transduction. AB - In response to a meiosis-inducing hormone, 1-methyladenine (1-MA), starfish oocytes undergo reinitiation of meiosis with germinal vesicle breakdown. The 1-MA initiated signal is, however, inhibited by prior microinjection of pertussis toxin into the oocytes, suggesting that a guanine nucleotide-binding protein (G protein) serving as the substrate of pertussis toxin is involved in the 1-MA receptor-mediated signal. We thus investigated properties of 1-MA receptors by means of binding of the radiolabeled ligand to the oocyte membranes. There were apparently two forms of 1-MA receptors with high and low affinities in the membranes. The high-affinity form was converted into the low-affinity one in the presence of a non-hydrolyzable analogue of GTP. A 39-kDa protein, which had been identified as the alpha-subunit of the major substrate G protein for pertussis toxin, was also ADP-ribosylated by cholera toxin only when 1-MA was added to the membranes. The ADP-ribosylated 39-kDa alpha-subunit could be immunoprecipitated with antibodies raised against the carboxy-terminal site of mammalian inhibitory G-alpha. These results indicate that 1-MA receptors are functionally coupled with the 39-kDa pertussis toxin-substrate G protein in starfish oocyte membranes. PMID- 1632763 TI - Gene synthesis and expression in E. coli for pump, a human matrix metalloproteinase. AB - The gene for PUMP (putative metalloproteinase), a human matrix metalloproteinase, was synthesized by a PCR-based method. The DNA fragment of 546 bases containing the PUMP gene was generated by overlap extension of six long oligonucleotides (length ranging from 101 to 116 bases) and subsequent amplification by two short terminal oligonucleotide primers (length from 20 to 48 bases) in one pot without using restriction and ligation enzymes. The synthetic gene was cloned into a T7 expression vector in two ways to express PUMP as a non-fusion protein. Both constructs showed high level expression in E. coli. PMID- 1632764 TI - Nitric oxide from endothelium and smooth muscle modulates responses to sympathetic nerve stimulation: implications for endotoxin shock. AB - The influence of nitric oxide (NO) on vascular responses to transmural stimulation (TNS) of noradrenergic nerves was studied in isolated rings of rat iliac arteries. TNS produced frequency-dependent contractions in all vessels. The NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) significantly enhanced TNS responses in intact vessels, but not in those in which the endothelium had been removed. However, in endothelium-denuded rings incubated for 8 hours, L-NMMA increased the contractions induced by nerve stimulation, an effect which was prevented by treatment with dexamethasone or cycloheximide, and enhanced by incubation with lipopolysaccharide and gamma-interferon. Addition of L-arginine reversed the effect of L-NMMA in intact rings; however, it significantly decreased below control values TNS-induced contractions in vessels without endothelium. The results indicate that a) the arterial response to noradrenergic nerve stimulation is modulated by NO originating either in endothelial cells or in smooth muscle cells after induction of NO synthase activity, and b) once NO synthase is induced, the limiting step in NO production is the availability of the substrate L-arginine. An overproduction of vascular NO in the presence of endotoxin or other inflammatory stimuli may prevent the vascular response to sympathetic stimuli and contribute to the vasodilation observed in inflammation or endotoxic shock. PMID- 1632765 TI - Biosynthesis of trans,trans,trans-geranylgeranyl diphosphate by the cytosolic fraction from rat tissues. AB - The cytosolic fractions from rat liver, brain, kidney, spleen and testis demonstrate the capacity to synthesize two products from [3H]isopentenyl diphosphate, i.e., farnesyl diphosphate and geranylgeranyl diphosphate. The highest rate of geranylgeranyl diphosphate synthesis was found in brain, testis and spleen, accounting for up to 30% of the total incorporation of radioactivity under optimal conditions. In all tissues examined the geranylgeranyl diphosphate formed was identified as the trans,trans,trans-isomer. The ratio of geranylgeranyl diphosphate to farnesyl diphosphate produced was specific for the tissue investigated and could be altered by the addition of divalent cations. The results in this study demonstrate the presence of a specific trans,trans,trans geranylgeranyl diphosphate synthetase showing high affinity for farnesyl diphosphate. PMID- 1632766 TI - Effects of epidermal growth factor on apo B mRNA levels and apo B accumulation in the media of primate hepatocytes in culture. AB - EGF has been shown to augment albumin and apolipoprotein A-I secretion by cynomolgus monkey hepatocytes in primary culture without stimulating cell division. This study was undertaken to determine what effect EGF had on apo B secretion by those hepatocytes. The results indicate that EGF (3 nM final concentration) severely inhibits the rate at which apo B accumulates in the culture medium of primate hepatocytes. That effect was evident within 48 hours of treatment, and by 72 hours the rate that apo B accumulated was less than half that of cells treated with a hormone-free medium. However, the apo B mRNA levels in the EGF-treated cells were more than double those of hepatocytes given the hormone-free medium. These data indicate that EGF has a potent effect on the rate at which apo B accumulates in the culture medium of primate hepatocytes and that the effect is independent of apo B gene expression. PMID- 1632767 TI - Intermolecular homologies of human interferon-alpha. AB - Human interferon-alpha 2 (IFN) was analyzed by homology search computer program with the use of protein primary structures data bases. Results indicate that four domains with heightened ability to form homology pairs with different proteins exist in the IFN molecule. These domains occupy regions 35-56, 72-85, 97-110 and 124-136, mainly between the alpha-helical cylinders on the tertiary structure models. Additionally, results show in IFN structure the presence of amino-acid motifs that create the opportunity for this cytokine to influence directly the processes of DNA functioning in cell nuclei. PMID- 1632768 TI - Enhanced expression of membrane phosphoproteins tyrosine phosphorylation in estrogen-induced kidney tumors. AB - We demonstrate for the first time that the expression of tyrosine containing membrane phosphoproteins is elevated in estrogen-induced kidney tumors, which is evident from both the types of experiments, i.e., alkali-resistant phosphorylation of membrane proteins and immunoprecipitation of tyrosine containing phosphoproteins. Tyrosine phosphorylation of proteins or peptides was modulated by the growth factors (EGF, IGF-I) and by the inhibitors of tyrosine protein kinase(s). The kinetic analyses revealed that tumor membranes have high affinity and catalytically more efficient tyrosine phosphorylating kinase enzyme(s) compared to that of normal membranes which have low affinity and catalytically less efficient kinase enzyme(s). It is proposed that overexpression of tyrosine containing membranal phosphoproteins may be involved in the induction and growth of estrogen-induced renal neoplasm. PMID- 1632770 TI - Characterization of a novel arachidonic acid-derived neutrophil chemoattractant. AB - The oxidation of arachidonic acid in a superoxide-generating environment results in the formation of a potent chemoattractant that appears to be identical to a chemotactic material generated by hepatocytes when they metabolize alcohol. The product was extracted, chromatographed and characterized by physical methods including GC/MS. The physical properties are consistant with the parent structure: 19-hydroperoxy, 20-hydroxyarachidic acid. This novel saturated 20 carbon product, derived from arachidonic acid by free radical-generating reactions, may play a role in the neutrophilic infiltration observed during the course of acute alcoholic hepatitis. PMID- 1632769 TI - Cytokines stimulate lipolysis and decrease lipoprotein lipase activity in cultured fat cells by a prostaglandin independent mechanism. AB - We previously showed that indomethacin blocked the effect of tumor necrosis factor (TNF) and other cytokines on lipolysis. We now show that TNF stimulates prostaglandin (PG) production, enhances lipolysis and decreases lipoprotein lipase (LPL) activity in 3T3-F442A adipocytes and indomethacin blocks these activities, suggesting that the actions of TNF are mediated by PG's. However, exogenous PGE2 at the levels induced by TNF is not sufficient to affect lipolysis or LPL activity and low doses of indomethacin and flurbiprofen block PG production without affecting TNF's action. Interleukin-1 and interferon-alpha and gamma induce lipolysis and decrease LPL activity but do not stimulate much PG production. These results demonstrate that cytokines enhance lipolysis and decrease LPL activity in 3T3 adipocytes by a PG independent mechanism. PMID- 1632771 TI - Angiotensin II receptor subtypes play opposite roles in regulating phosphatidylinositol hydrolysis in rat skin slices. AB - Among the many functions of angiotensin II (Ang II) it now appears that Ang II is a growth factor. The concentration of Ang II in rat skin has been shown to increase during wound healing. To investigate the intracellular effect of Ang II in skin we determined the levels of total cytoplasmic inositol phosphates after incubation of skin slices with different doses of Ang II. 10(-6) M of Ang II increased significantly the phosphatidylinositol (PI) hydrolysis, and the effect was dose dependent up to 10(-4) M Ang II. The majority of inositol phosphates yielded after 1 hour incubation in the presence of lithium was InsP1, with lesser amount of InsP2. Losartan, the Ang II AT1 antagonist, at a dose of 10(-4) M blocked the effect of Ang II, while PD123319, the Ang II AT2 antagonist, had no antagonistic action; PD123319 at the higher dose of 10(-3) M, however, potentiated the effect of Ang II on PI hydrolysis. The results suggest that PI hydrolysis is a second messenger system for Ang II in rat skin. Also, the two subtypes of Ang II receptors mediate opposite effects on PI hydrolysis: Ang II binding to AT1 receptors increases inositol phosphate production, while Ang II binding to AT2 receptors decreases inositol phosphate production. PMID- 1632772 TI - Characterization of mouse inhibin alpha gene and its promoter. AB - Inhibin suppresses the pituitary secretion of FSH but not LH. The two forms of inhibin are composed of a common alpha subunit linked to either a beta A or a beta B subunit. The mouse inhibin alpha gene was isolated and shown to have two exons spanning a 1.7 Kb intron. The proximal 5' flanking region has neither TATA and CAAT boxes nor GC-rich area. Using the 5' flanking region of mouse inhibin alpha gene linked to luciferase gene, transfection of rat granulosa cells indicated that the first 165 bp of the promoter region is required for basal expression. The mouse inhibin alpha genomic clone should be useful for analysis of hormonal control of inhibin alpha transcription and the generation of mice with targeted deletion of this gene. PMID- 1632773 TI - Low density lipoprotein inhibits accumulation of nitrites in murine brain endothelial cell cultures. AB - Endothelial cells produce nitric oxide which is considered to serve as a major source of endothelial derived relaxing factor activity. It has been demonstrated that activation of mouse brain endothelium by TNF-alpha and IFN-gamma led to accumulation of nitrite which is presumably formed by oxidation of nitric oxide. A number of studies suggest that reactive oxygen species produced by cytokine activated cells are involved in the conversion of nitric oxide to nitrites and nitrates. We investigated whether low density lipoprotein (LDL), acting as a radical scavenger, is able to inhibit nitrite accumulation in mouse brain endothelial cell cultures and in a cell-free system in which sodium nitroprusside was used as a source of nitric oxide. A comparison of these two models indicates the active involvement of LDL in suppressing nitrite accumulation in murine endothelial cultures. PMID- 1632775 TI - Suppression of crossbridge motions of isolated thick myofilaments in ATP-free medium by thiourea. AB - Thiourea is known to suppress the contractile response of Mytilus anterior byssus retractor muscle and toad sartorious muscle following electrical or chemical stimulation without abolishing of the electrical responses. In addition, it blocks the shortening of glycerinated sartorious muscle induced by Ca2+. With dynamic laser light scattering method we found that thiourea suppresses the increase of the average linewidth of the photoelectron count autocorrelation function, gamma, of isolated thick filaments of Limulus striated muscle induced by depletion of ATP. The results obtained suggest that thiourea prevents the crossbridges from moving away from the thick myofilament backbones which will, in turn, prohibit the crossbridges from interacting with the thin myofilaments. PMID- 1632776 TI - Photothermal spectroscopy of bacteriochlorophyll-lipoprotein complexes. AB - Photoacoustic spectra at room and 85 K temperatures as well as photothermal beam deflection spectra of bacteriochlorophyll-lipoprotein complexes from purple bacterium Chromatium minutissimum were measured. Spectra were compared and obtained differences were tentatively explained by various inertion of these two methods. Photothermal beam deflection method measure the heat which is generated in close surroundings of absorbing pigment molecule, whereas usage of more inert photoacoustic signal is averaged over contributions from various pigments located in a larger sample volume and therefore is similar to absorption spectra. PMID- 1632774 TI - Androst-5-ene-7,17-dione: a novel class of suicide substrate of aromatase. AB - 5-En-7-one steroid 1 was found to be a potent inhibitor of aromatase. This along with its 19-hydroxy derivative 7 was characterized as suicide substrate of human placental aromatase (k(inact)'s of 0.069 and 0.058 min-1 and KI's of 143 nM and 11.1 microM, respectively, for steroids 1 and 7). The results suggest that the 19 oxygenation would be involved in the irreversible inactivation of aromatase by the 5-en-7-one steroids. PMID- 1632777 TI - Membrane fusion of influenza virus with phosphatidylcholine liposomes containing viral receptors. AB - pH-dependent membrane fusion of influenza virus with liposomes made of phosphatidylcholine was studied by the spin-labelling method. Efficiency of viral fusion with liposomes composed of dimyristoyl phosphatidylcholine or dipalmitoyl phosphatidylcholine was considerably lower compared to dioleoyl phosphatidyl choline or egg yolk phosphatidylcholine, suggesting importance of unsaturation of acyl chains of lipid bilayers. Reconstitution of specific viral receptors such as Glycophorin or sialylparagloboside strongly enhanced fusion with liposomes composed of dimyristoyl phosphatidylcholine. A direct comparison between the activities of the receptors showed that Glycophorin was about 50 times more effective than sialyparagloboside at the same receptor/phosphatidylcholine molar ratio. PMID- 1632778 TI - Increased plasma post-heparin diamine oxidase activity and plant sterol levels in streptozotocin diabetic rat. AB - Plasma post-heparin diamine oxidase (DAO) activity and plasma levels of plant sterols were examined in streptozotocin diabetic rats fed with chow containing plant sterols, to investigate the enzyme activity in relation to the morphological changes of small intestine as well as sterol absorption in the diabetic rats. Diabetic rats showed increased small intestinal mass and surface area compared with control rats. Plasma post-heparin DAO activity and plant sterol level were also increased more than 2.5-fold in the diabetic rats. Insulin treatment improved these abnormalities. Plasma DAO activity correlated to both the small intestinal hyperplastic change and plasma plant sterol levels. These results indicate that plasma post-heparin DAO activity may be used as a marker of intestinal hypertrophy as well as ability to absorb dietary sterols. PMID- 1632779 TI - Cloning and disruption of the cefG gene encoding acetyl coenzyme A: deacetylcephalosporin C o-acetyltransferase from Acremonium chrysogenum. AB - Acetyl CoA: deacetylcephalosporin C o-acetyltransferase(DCPC-ATF) catalyses the final step in the biosynthesis of cephalosporin C (CPC) in Acremonium chrysogenum. The gene encoding DCPC-ATF, cefG, has been isolated from an A. chrysogenum genomic library using a DCPC-ATF cDNA probe. Nucleotide sequence analysis revealed that cefG contains two short introns of 79bp and 65bp. The gene was found to be closely linked to the cefEF gene encoding deacetoxycephalosporin C synthetase/deacetylcephalosporin C synthetase, which catalyses the preceding two steps in the pathway. The two genes are separated by a 1114 bp segment from which they are divergently transcribed. Introduction of the cloned cefG gene to A.chrysogenum resulted in an increased level of DCPC-ATF activity. A plasmid carrying a cefG gene interrupted in the coding region by a selectable marker for resistance to hygromycin B was constructed and used to disrupt the cefG locus in A.chrysogenum. The cefG-disrupted strains were found to lack the ability to produce CPC, and accumulated its precursor, deacetylcephalosporin C in the culture broth. Southern hybridization analysis confirmed that the disruption resulted from a gene replacement event at the cefG locus. PMID- 1632780 TI - A novel saccharide structure, Xyl 1----3 Gal 1----(SO3-)3,4 Fuc----, is present in acrosome reaction-inducing substance of the starfish, Asterias amurensis. AB - The jelly coat of echinoderm eggs contains a glycoconjugate, acrosome reaction inducing substance (ARIS), that is essential for triggering the acrosome reaction in homologous spermatozoa. In the starfish, Asterias amurensis, ARIS is a sulfated glycoprotein of an apparent molecular size of greater than 10(7). Since its biological activity is dependent mostly on its sugar moiety, oligosaccharides liberated by hydrolysis with 10 mM H2SO4 for 60 min at 100 degrees C from pronase digests of ARIS (P-ARIS) were chemically analyzed. The main oligosaccharide purified by high-performance anion-exchange chromatography was determined to be Xyl1----3Gal1----(SO3-)3,4Fuc by compositional analysis and FAB mass spectrometry. This structure indicates that ARIS possesses a novel saccharide chain having sulfated fucose as an internal residue. PMID- 1632781 TI - Rat hypothalamic proopiomelanocortin messenger RNA is unaffected by adrenalectomy. AB - The negative feedback control of hypothalamic cortocotrophin releasing factor (CRF) and anterior pituitary proopiomelanocortin (POMC) by corticosteroids is well understood. However, less is known about the mechanisms that regulate POMC gene expression in the arcuate nuclei in the medial basal hypothalamus (MBH). Using a sensitive and specific S1 endonuclease protection assay, we have examined the effect of adrenalectomy on POMC mRNA in the rat MBH and pituitary. Our results show that adrenalectomy does not change POMC mRNA levels in the MBH at 7 or 14 days post surgery. The neurointermediate lobe of the pituitary was similarly unaffected by adrenalectomy, while in the anterior lobe, POMC mRNA increased 7-10 fold at both time points, effects that were prevented by dexamethasone treatment. We conclude that while POMC mRNA in the anterior lobe of the pituitary is regulated by plasma glucocorticoids, in the MBH and neurointermediate lobe, it is not. PMID- 1632782 TI - Posttranslational isoprenylation of rho protein is a prerequisite for its interaction with mastoparan and other amphiphilic agents. AB - The amphiphilic agents melittin, compound 48/80 and mastoparan inhibit ADP ribosylation of porcine brain rho protein by Clostridium botulinum exoenzyme C3. However, ADP-ribosylation of recombinant rhoA expressed in E.coli was not inhibited by these agents. Accordingly, steady state GTP hydrolysis by recombinant rhoA was not stimulated by mastoparan, whereas GTP hydrolysis by porcine brain rho was stimulated 2.5-fold in the presence of this wasp venom. After microinjection of recombinant rhoA into Xenopus laevis oocytes the inhibitory effect of mastoparan on C3 ADP-ribosylation was restored. The data suggest that the amphiphilic agents tested are only active at the posttranslationally processed form of rho and that they exert their effects via the C-terminal end. PMID- 1632783 TI - Kupffer cells play a major role in insulin-mediated hepatic glucose uptake in vivo. AB - The effect of insulin on the in vivo glucose utilization by different hepatic cells was investigated using the euglycemic, hyperinsulinemic clamp, combined with the 2-deoxyglucose tracer technique. Rats were infused with insulin at a rate of 2.8 or 9.0 mU/min/kg for 220 min, resulting in plasma concentrations of the hormone of about 80 microU/ml and 340 microU/ml, respectively. Glucose use by the whole liver was elevated by more than 200% following insulin. However, glucose uptake by the parenchymal cells was only elevated by 50-60%. By contrast nonparenchymal cells were more responsive to insulin. Glucose uptake by endothelial cells was increased 100% and Kupffer cells displayed the most marked response to insulin showing a 3- to 6-fold increase in glucose uptake. These data indicate that the sinusoidal nonparenchymal cells are the major sites of the insulin-mediated increased glucose utilization by the liver. PMID- 1632784 TI - Complement inhibitor C4-binding protein in amyloid deposits containing serum amyloid P in Alzheimer's disease. AB - Complement C4-binding protein (C4BP) is a plasma protein that complexes with serum amyloid P and is involved in inhibition of the complement cascade. We used immunochemical methods to demonstrate C4BP in brains of subjects with Alzheimer's disease and normal controls. C4BP antibodies stained cerebral amyloid deposits that were indistinguishable from those recognized by antibodies to serum amyloid P or by thioflavin S. Immunoblots of solubilized proteins from cerebral cortex, cerebral microvessels and cerebrospinal fluid showed specific antibody reactivity to 70-90 kDa bands. Our results suggest the involvement of complement regulatory proteins in the pathogenesis of Alzheimer's disease. PMID- 1632785 TI - In vitro interaction between Saccharomyces cerevisiae CDC25 and RAS2 proteins. AB - In Saccharomyces cerevisiae the CDC25 protein is a positive regulator of RAS/cAMP pathway [1-4], enhancing the GDP-releasing rate of RAS2 protein [5]. In this work we have tried to detect a direct interaction between CDC25 and RAS2 gene products. The results indicate that both the whole RAS2 protein and a truncated version that lacks approximately 25 C-terminal residues interact specifically with the CDC25 protein. On the contrary, a derivative of RAS2 that lacks the 112 C-terminal residues as well as the p21TI-ras is not able to bind the CDC25 protein in our assay conditions. The 310 C-terminal aminoacids of CDC25 bind RAS2 while a C-terminus deletion within this aminoacid stretch abolishes the binding. The possible physiological significance of these findings is discussed. PMID- 1632786 TI - Mitochondrial tRNA(Ile) mutation in fatal cardiomyopathy. AB - A patient with mitochondrial encephalomyopathy who died from progressive intractable cardiac failure at the age of 18 is reported. At the age of 4, he presented with short stature, but multiorgan disorders including deafness, focal glomerulosclerosis, epilepsy and dilated cardiomyopathy appeared later in his clinical course. Laboratory tests showed hyperlactatemia and hyperpyruvatemia. Histopathological findings demonstrated mitochondrial myopathy with ragged red fibers and focal cytochrome C oxidase-deficient fibers in skeletal and cardiac muscles. The activity of cytochrome C oxidase was 30% less than the control level in skeletal muscle. Sequencing of the entire mitochondrial tRNA genome revealed a novel point mutation in the tRNA(Ile) region (nt 4269). This A-to-G substitution was found in none of the 30 controls by screening using mispairing PCR and Ssp I digestion methods, suggesting that this new mutation was pathogenic in our case. PMID- 1632787 TI - A novel low-density lipoprotein with large amounts of phospholipid found in the egg yolk of crustacea sand crayfish Ibacus ciliatus: its function as vitellogenin degrading proteinase. AB - Low-density lipoprotein (LDL) with large amounts of phospholipid but not triacylglycerol was isolated from the egg yolk of crustacea sand crayfish Ibacus ciliatus as well as lipovitellin. LDL possessed vitellogenin-degrading proteinase activity. Hemolymph vitellogenin was degraded by incubating with LDL at pH 4.5 for 72 hr at 35 degrees C and apolipoprotein profiles of vitellogenin degraded by LDL were very similar to those of lipovitellin in the egg. PMID- 1632788 TI - p56lck stably associates with a 115 kDa substrate. AB - Using antibodies directed against p56lck, we have identified a 115 kDa protein (p115) that is specifically immunoprecipitated with p56lck from whole cell lysates. The p56lck/p115 complex is stable in the presence of nonionic detergents. p115 becomes phosphorylated on tyrosine residues in p56lck immune complex kinase assays. Treatment of whole cells with 12-O-tetradecanoyl phorbol 13-acetate decreases the subsequent tyrosine phosphorylation of p115 in immune complex kinase assays. PMID- 1632789 TI - Stimulatory effects of estrogen and progesterone on proliferation and differentiation of normal human osteoblast-like cells in vitro. AB - Here we report that osteoblast-like cells derived from female and male adult human trabecular bone are able to directly respond to 17 beta-estradiol (E2) and progesterone (P). In short-term (1 day) cultures using serum-free and phenol red free medium, both steroid hormones were found to stimulate DNA synthesis and growth of the human osteoblast-like cells. P was more potent in stimulating osteoblast growth compared to E2. On the other hand, E2 showed a stronger differentiation-inducing effect as determined by analysis of the number of cells displaying cytochemical alkaline phosphatase (AP) activity, a marker for the mature osteoblast phenotype. Combination of E2 and P resulted in a further increase in DNA synthesis, but did not further affect the number of cells expressing AP activity. In conclusion, female sex steroids may be involved in regulating bone mass in human adults via a direct anabolic action on the bone forming cells. PMID- 1632790 TI - Growth inhibition of leukemia cell line CEM-C1 by farnesol: effects of phosphatidylcholine and diacylglycerol. AB - Acute leukemia cells of the established line CEM-C1 were treated during growth in serum-free medium with various concentrations of trans-trans farnesol. At concentrations ranging from 9.0 to 31.5 microM, farnesol inhibited growth of these cells without causing cell lysis. This effect was preceded by very rapid inhibition of choline incorporation in cellular lipid fraction. The growth inhibitory effect was prevented to a large extent by incubation with phosphatidylcholine or diacylglycerol. PMID- 1632791 TI - The cysteine residues in the carboxy terminal domain of tropoelastin form an intrachain disulfide bond that stabilizes a loop structure and positively charged pocket. AB - Analysis of purified bovine tropoelastin with Ellman's reagent and [14C]iodoacetamide demonstrated that the only two cysteine residues in the molecule form an intrachain disulfide bond. Molecular modeling suggests that the cysteine residues are juxtaposed as the result of a tight turn that produces an antiparallel beta structure. Protruding from the C-terminal end of the turn is the sequence Arg-Lys-Arg-Lys which forms the floor of a positively charged pocket created by the extension of the arginine and lysine side chains on opposite sides of the peptide chain perpendicular to the plane of the turn. The side chain of a conserved lysine residue in the disulfide-bonded loop forms the top of the pocket. This positively charged pocket may define a binding site for acidic microfibrillar proteins that mediate elastic fiber assembly. PMID- 1632792 TI - Synergistic action of two oxysterols in the lowering of HMG-CoA reductase activity in CHO-K1 cells. AB - 3 beta-Hydroxy-5 alpha-cholest-8(14)-en-15-one (I) and (25R)-26 hydroxycholesterol (II), both potent regulators of sterol biosynthesis, have been found to show synergism in the reduction of the levels of HMG-CoA reductase activity in CHO-K1 cells. When equimolar concentrations of I and II were added in combination, synergistic reduction (p less than 0.0001) of enzyme activity was observed at total oxysterol concentrations of 0.1 microM, 0.2 microM, and 0.5 microM. Maximal synergistic effect in the lowering of reductase activity (28% greater than predicted) was observed at 0.1 microM total oxysterol concentration. Five additional experiments conducted with 50 nM oxysterols confirmed the synergistic effect at 0.1 microM total sterol concentration. These results suggest that the in vivo importance of I and II may be greater than that anticipated on the basis of the concentrations of the individual sterols. PMID- 1632793 TI - On the mechanisms of Ku protein binding to DNA. AB - The in vitro DNA-binding activity of Ku protein, a heterodimer of 70 and 86 kDa subunits, was studied using affinity-purified protein. Ku protein bound to different DNA probes and displayed a multiple-band pattern in band mobility shift assays. The protein-DNA complex formation was effectively blocked by different DNA competitors, indicating a non-sequence specific binding of Ku protein to DNA; no preference of binding of Ku protein to regulatory sequences derived from U1 snRNA, U6 snRNA or nucleolar protein p120 genes was observed. The number and size of the Ku protein-DNA complexes increased with increasing of the protein concentration and the size of DNA probe, suggesting that the protein accumulates on the DNA fragment until saturation of the binding sites. In UV-crosslinking experiments, the binding of Ku protein to DNA was shown to start with the 70 kDa subunit contacting free DNA ends. PMID- 1632794 TI - Volatile anesthetics selectively alter [3H]ryanodine binding to skeletal and cardiac ryanodine receptors. AB - The effect of clinical concentrations of volatile anesthetics on ryanodine receptors of cardiac and skeletal muscle sarcoplasmic reticulum was evaluated using [3H]ryanodine binding. At 2 volume percent, halothane and enflurane stimulated binding to cardiac SR by 238% and 204%, respectively, while isoflurane had no effect. In contrast, halothane and enflurane had no effect on [3H]ryanodine binding to skeletal ryanodine receptors, while isoflurane produced a significant stimulation. These results suggest that volatile anesthetics interact in a site-specific manner with ryanodine receptors of cardiac or skeletal muscle to effect Ca2+ release-channel gating. PMID- 1632795 TI - NADPH-dependent inhibition of lipid peroxidation in rat liver microsomes. AB - Microsomal NADPH-driven electron transport is known to initiate lipid peroxidation by activating oxygen in the presence of iron. This pro-oxidant effect can mask an antioxidant function of NADPH-driven electron transport in microsomes via vitamin E recycling from its phenoxyl radicals formed in the course of peroxidation. To test this hypothesis we studied the effects of NADPH on the endogenous vitamin E content and lipid peroxidation induced in liver microsomes by an oxidation system independent of iron: an azo-initiator of peroxyl radicals, 2,2'-azobis (2,4-dimethylvaleronitrile), (AMVN), in the presence of an iron chelator deferoxamine. We found that under conditions NADPH: (i) inhibited lipid peroxidation; (ii) this inhibitory effect was less pronounced in microsomes from vitamin E-deficient rats than in microsomes from normal rats; (iii) protected vitamin E from oxidative destruction; (iv) reduced chromanoxyl radicals of vitamin E homologue with a 6-carbon side-chain, chromanol-alpha-C-6. Thus NADPH-driven electron transport may function both to initiate and/or inhibit lipid peroxidation in microsomes depending on the availability of transition metal catalysts. PMID- 1632796 TI - Feedback repression of polyamine uptake into mammalian cells requires active protein synthesis. AB - Two mammalian cell lines, rat hepatoma (HTC) and Chinese hamster ovary (CHO), were fed 10 to 50 microM spermidine while changes were monitored in intracellular polyamine levels and spermidine uptake activity. Normal feedback control preventing excessive polyamine uptake was found to be completely blocked by the addition of inhibitors of protein synthesis at the time of polyamine exposure. Under these conditions the cells accumulated abnormally high, toxic concentrations of spermidine. Further, continuous protein synthesis was needed to maintain repression of polyamine transporter proteins that had been inhibited previously by normal or elevated intracellular polyamines. These results suggest that a major factor in the regulation of polyamine uptake is the rapid, reversible inactivation of existing polyamine carrier molecules by an unstable protein whose synthesis is stimulated by intracellular polyamines. PMID- 1632797 TI - Apolipoprotein A-1 interacts with the N-terminal fusogenic domains of SIV (simian immunodeficiency virus) GP32 and HIV (human immunodeficiency virus) GP41: implications in viral entry. AB - Previous studies showed that apoA1, the major protein component of HDL (High Density Lipoprotein), inhibited HIV infectivity and virus-induced syncytia formation. The mechanism of inhibition is unknown. We bring here evidence that the amphipathic helices of apoA1 interact with the N-terminal peptides of SIV gp32 and HIV gp41. These peptides have been shown to be associated with the initial steps of the fusion between the host cell and the virus. Binding of apoA1 to these peptides prevents the insertion of the fusogenic domains into the cell membrane and inhibits the fusion and the entry of the virus into the host cell. PMID- 1632798 TI - Studies on the intracellular Ca2+, protein kinase activity, and ATP contents of cisplatin- and rIFN-Y-treated non-adherent mononuclear cells. AB - The in vitro effect of cisplatin or rIFN-Y on the intracellular free calcium, protein kinase activity and ATP content of non-adherent mononuclear cells (nMNC) from human peripheral blood was assessed. We observed that treatment of nMNC with cisplatin enhanced the [Ca2+]i, ATP level, and protein kinase activity; whereas rIFN-Y-treated nMNC showed significant rises in ATP level and protein kinase activity only. We also observed that cisplatin-treated nMNC showed an instantaneous rise in [Ca2+]i when NK-sensitive K562 cells were added to the effector cells. PMID- 1632799 TI - Use of immunoadsorbent column chromatography for improved purification of arylsulfatase B from human placenta. AB - A simple and rapid procedure involving immunoadsorbent column chromatography has been developed for the isolation of lysosomal arylsulfatase B from human placenta. Using this method, we purified the enzyme over 20,000-fold with better recovery (16%) compared to that achieved by the conventional procedure. The enzyme appeared to be homogeneous and had an apparent molecular weight of 58,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under nonreducing conditions. The purified enzyme migrated as two bands with apparent molecular weights of 43,000 and 8,000 by reductive SDS-PAGE. PMID- 1632800 TI - Pluronic micelles as a tool for low-molecular compound vector delivery into a cell: effect of Staphylococcus aureus enterotoxin B on cell loading with micelle incorporated fluorescent dye. AB - Micelles of pluronic P85 (poly(oxyethylene)-poly(oxypropylene) block copolymer) are used as microcontainers for in vitro delivery of fluorescein into Jurkat and MDCK cells. In order to target the fluorescein containing micelles into the cell, Staphylococcus aureus enterotoxin B (SEB) is covalently conjugated with a pluronic molecule and the conjugate is incorporated into the micelle content. The incorporation of SEB capable of receptor-mediated endocytosis results in a drastic enhancement of the efficiency of cell loading with the fluorescent dye. This effect is not observed under the conditions (4 degrees C) when endocytosis is abolished. PMID- 1632801 TI - Adenosine deaminase from bovine brain: purification and partial characterization. AB - Bovine brain adenosine deaminase cytoplasmatic form was purified about 450 fold by salt fractionation, column chromatography on DEAE-cellulose, octyl-sepharose 4B and affinity chromatography on CH-sepharose 4B 9-(p-aminobenzyl)adenine. The purified enzyme was homogeneous on disc gel electrophoresis; the enzyme had a molecular mass of about 65 kDa with an isoelectric point at pH 4.87. The Km values for adenosine and 2'-deoxyadenosine were 4 x 10(-5) and 5.2 x 10(-5) M, respectively. The enzyme showed a great stability to temperature with a half life of 15 hours at 53 degrees C significantly different compared to that known for other mammalian forms of this enzyme. Aza and deaza analogs of adenosine and erythro-9-(2-hydroxy-3-nonyl) adenine were good inhibitors of the bovine brain enzyme with little difference with respect to those reported for the adenosine deaminases purified from other sources. Kinetic constants for the association and dissociation of coformycin and 2'-deoxycoformycin with the bovine brain adenosine deaminase are reported. PMID- 1632802 TI - DIDS-effect on Ser/Thr- and Tyr-phosphorylation of membrane proteins in human erythrocytes. AB - Band 3, the major transmembrane multifunctional protein of human erythrocytes, has been found to be phosphorylated-dephosphorylated on both Ser/Thr- and Tyr residues by specific protein kinases and protein phosphatases. The results reported here would indicate that the ghosts prepared from human erythrocytes pretreated with DIDS, well known inhibitor of band 3-mediated anion transport, exhibit a markedly reduced Ser/Thr-phosphorylation of spectrin and band 3, when incubated with [gamma-32P]ATP in the presence of Mg2+. On the other hand, Tyr phosphorylation of this latter protein is practically unchanged or even slightly enhanced. This suggests that Ser/Thr- and Tyr-phosphorylation of band 3 display a different functional role. PMID- 1632803 TI - Expression of pS2 gene in human breast cancer cell line MCF-7 is controlled by retinoic acid. AB - We established a simplified method for the quantitative measurement of pS2 mRNA using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Expression of the pS2 gene, which is transcriptionally induced by estrogen in breast cancer cell line MCF-7 cells, can be repressed by retinoic acid (RA) in unstimulated cells. The suppressive effect of RA on pS2 mRNA was inhibited by cycloheximide. PMID- 1632804 TI - Inhibition of Helicobacter pylori glycosulfatase activity toward gastric sulfomucin by nitecapone. AB - A glycosulfatase activity toward gastric sulfomucin was identified in the extracellular material elaborated by H. pylori. The enzyme exhibited maximum activity at pH 5.7 in the presence of Triton X-100 and CaCl2, and displayed on SDS-PAGE an apparent molecular weight of 30kDa. The H. pylori glycosulfatase effectively caused desulfation of N-acetylglucosamine-6-sulfate and galactose-6 sulfate of the carbohydrate chains of mucins, as well as that of glucose-6 sulfate of glyceroglucolipids, but was ineffective towards galactosyl- and lactosylceramide sulfates which contain galactose-3-sulfate. The glycosulfatase activity towards human gastric sulfomucin was affected by an antiulcer agent, nitecapone, which at its optimal concentration (100 micrograms/ml) caused a 61% inhibition. The results show that H. pylori through its glycosulfatase activity causes desulfation of sulfated mucins and glyceroglucolipids of the protective mucus layer, and that nitecapone is able to interfere with this detrimental action. PMID- 1632805 TI - A simple method for detecting protein antigens in flour. AB - Wheat, barley, rye or oat flour was dissolved in 0.2N NaOH using magnetic stirring followed by sonication. The ensuing clear solutions contained 95% of protein in the dry matter. Aliquots were electrophoresed on 12% polyacrylamide gels which were either stained with Coomassie brilliant blue or Western-blotted on nitrocellulose membrane. Incubation of the latter with serum from persons sensitized to flours allowed the detection of antigenic flour protein classes. It seems that many antigens are present in common kitchen flour. PMID- 1632806 TI - Unfolding of lysozyme by breaking its disulphide bridges results in exposure of hydrophobic sites. AB - The interaction of 1-anilino-naphthalene-8-sulphonate (ANS), a probe whose fluorescence is strongly dependent on hydrophobicity of the environment, with native lysozyme and lysozyme partially unfolded by breaking the disulphide bridges and reacting the free -SH groups with iodoacetamide, has been investigated. Monitoring the intensity of ANS fluorescence and the position of the emission maximum in the presence of native and partially unfolded lysozyme indicated that unfolding resulted in the exposure of hydrophobic sites. Hydrophobic sites could not be detected when native and partially unfolded lysozyme were denatured with urea or guanidinium chloride. Protein components of the cells export machinery like 'chaperones' associate only with partially unfolded proteins and not native, folded proteins. Hence, hydrophobic regions of proteins, exposed on partial unfolding, could be the sites of recognition by 'chaperone' proteins. PMID- 1632807 TI - Phospholipid polar heads affect the generation of oxygen active species by Fe2+ autoxidation. AB - The possibility that phospholipid polar heads may influence Fe2+ reaction with molecular oxygen and, thus, the generation of oxygen active species was investigated. Dipalmitoyl phosphatidylcholine (DPPC) and DPPC/dipalmitoyl phosphatidic acid (DPPA) were utilized as model liposomes. Fe2+ oxidation, oxygen consumption, nitro blue tetrazolium reduction and 2-deoxyribose degradation were the parameters evaluated. Comparison of the results obtained clearly shows that the two types of polar heads differently affect iron chemistry. DPPC liposomes are ineffective. By contrast, Fe2+ oxidation by oxygen occurs in the presence of DPPC/DPPA liposomes. During this reaction, species able to reduce nitro blue tetrazolium and to degrade 2-deoxyribose are generated. The results obtained indicate that the polar heads of phospholipids, by influencing Fe2+ autoxidation, generate dangerous oxygen species which may exert an active role in the oxidation of the associated hydrophobic components of the phospholipids. PMID- 1632808 TI - Induction of ornithine decarboxylase by transcriptional inhibitors in quiescent thymocytes. AB - The transcriptional inhibitors actinomycin D and dichlororibofuranosylbenzimidazole induced ornithine decarboxylase activity in isolated, quiescent thymocytes, which otherwise did not show detectable levels of the enzyme. This paradoxical induction was transient and dependent on the presence of serum and continuous protein synthesis. However, alpha-amanitin, another inhibitor of transcription, did not affect ornithine decarboxylase activity. Dichlororibofuranosylbenzimidazole and actinomycin D were unable to enhance the activity of spermidine acetyltransferase or S-adenosyl-methionine decarboxylase, which are other inducible and short-lived enzymes involved in the metabolism of polyamines. PMID- 1632809 TI - Catabolism of platelet-activating factor by human colonic mucosa. Calcium dependence of the catabolizing enzymes. AB - The catabolism of platelet-activating factor (PAF) and lyso PAF by a supernatant fraction of human colon mucosa homogenates has been studied in vitro. PAF is initially catabolized to lyso PAF by mucosal enzymes via removal of its acetyl group. Incubates in Ca(2+)-free Tris with EDTA showed that the acetyl hydrolase was Ca2+ independent. Addition of the hydrolase inhibitor, phenyl methyl sulphonyl fluoride, significantly reduced the catabolism of PAF. Lyso PAF was further catabolized in at least two ways. An acyl group was incorporated into the sn-2 position of lyso PAF to give 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine (alkyl acyl GPC); this step was Ca2+ independent as shown by omitting Ca2+ and adding EDTA to the incubate. Formation of alkyl acyl GPC was confirmed by HPLC. Alternatively, choline was removed from the head group of lyso PAF by a calcium dependent lyso phospholipase D. Under the experimental conditions utilized a neutral lipid product was formed but significant amounts of the intermediate lysophosphatidic acid could not be detected. A substance with a chromatographic mobility of Rf = 0.8 on TLC plates having an intact phosphorylcholine head group was also formed but has not yet been identified. It is concluded that the human colon mucosa contains enzymes that actively catabolize pro-inflammatory PAF and lyso PAF. PMID- 1632810 TI - Comparative affinity of steroidal and non-steroidal antioestrogens, cholesterol derivatives and compounds with a dialkylamino side chain for the rat liver antioestrogen binding site. AB - Steroidal and non-steroidal antioestrogens, steroidal compounds with (disubstituted) dialkyl amino side chain, cholesterol derivatives, histaminic and (anti)-progestational compounds were tested for their ability to compete with [3H]tamoxifen for the specific antioestrogen binding site (AEBS) in the post mitochondrial fraction of rat liver homogenates. Relative binding affinity was highest for compounds with diethylamino or pyrrolidino ethoxy side chains. Affinity decreased with shortening of this side chain. No connection could be established between the carbon backbone of the compound and affinity, except for the presence of (sometimes aromatic) ring structures. Steroidal ring structures do not seem to be necessary for binding. The cholesterol derivatives, tested in our laboratory, showed very little affinity for the rat liver AEBS. Histamine, melatonin and the (anti)-progestational compounds showed no affinity for the AEBS; and we therefore conclude that the AEBS is not identical to receptors for these compounds. Results of these experiments could be useful in other investigations on the development of resistance of breast cancer to antioestrogens. PMID- 1632811 TI - The S-thiolation of hepatocellular protein thiols during diquat metabolism. AB - The effects of diquat metabolism on the protein thiol (PrSH) status of bis chloronitrosourea-pretreated hepatocytes have been studied. Using a conventional, dithionitrobenzene-based assay for free PrSH in trichloroacetic acid-precipitated protein, control levels of PrSHs (83 +/- 6 nmol/mg protein) were unaltered during the initial 60 min of incubation of the cells with 1 mM diquat. However, using a radiochemical method for the determination of glutathionylation of PrSH [Grimm et al., Biochim Biophys Acta 844: 50-54, 1985], in which the hepatocytes were prepared from diethylmaleate-pretreated animals and reloaded with reduced glutathione (GSH) in the presence of [35S]methionine and cycloheximide, oxidation of hepatocellular PrSH by stimulated S-thiolation with GSH could be demonstrated. The S-glutathionylation of the protein was maximal after 30 min of treatment of the cells and preceded the onset of membrane leakage. However, the quantity of GSH mixed disulfide formed was limited to a maximum of 1.4 +/- 0.4 nmol GSH/mg protein, indicating the oxidation of only 2% of the total hepatocellular PrSH by S-thiolation. This percentage depletion is below the working variability of the colourimetric PrSH assay utilized and indicates strongly the use of the S thiolation assay in the study of the possible effects of other redox-cycling cytotoxins on cellular PrSH status, as these may not be evident with conventional spectrophotometric techniques. The analysis of the cellular protein from diquat treated cells by SDS-PAGE and autoradiography indicated the S-glutathionylation of a variety of cellular proteins, including species with molecular masses 17, 24, 26, 30, 40, 43 and 46 kDa. Although the identities of these species are uncertain (the 30-kDa protein may be equivalent to carbonic anhydrase as reported by Rokutan et al., Biochemistry 179: 233-239, 1989), it may be that oxidative modification of these proteins by stimulated S-glutathionylation may be an important early event in the mechanism of the hepatotoxicity of diquat. PMID- 1632812 TI - Modulation of the levels of cytochromes P450 in rat liver and lung by dietary lipid. AB - This study was undertaken to investigate the effect of dietary lipid on the regulation of several constitutive P450 isozymes. Male Sprague-Dawley rats with body weights of 130-140 g were fed either a 20% corn oil (CO) diet or a fat-free (FF) diet for 4 days following 2 days of fasting. Using liver microsomes, the catalytic activities and immunochemically detectable protein levels of P450s 1A1 and 2, 2A1, 2B1 and 2, 2C11, 2E1, and 3A were determined. The microsomes from rats fed the 20% CO diet exhibited 2-fold higher levels in N-nitrosodimethylamine demethylase activity and P450 2E1 protein than those from rats fed the FF diet. The CO group also showed 2.5-fold higher levels in 6 beta-hydroxylation of testosterone and P450 3A protein than the FF group. In contrast, the CO diet did not affect the immunodetectable level of P450 2C11 protein and its catalytic activities such as benzphetamine demethylase activity and 2 alpha-hydroxylation of testosterone. P450 1A1 was not detectable in either group, but 1A2 was 2.5 fold higher in the CO group than in the FF group. In the liver, the P450 2B1 level was very low in both groups as measured by pentoxyresorufin dealkylase activity and the protein level, whereas 2B2 was 2.5-fold higher in the CO diet group. In lung microsomes from rats fed different amounts of CO, an inverse relationship was observed between the P450 2B1 level and the dietary CO level. The results suggest that the constitutive levels of P450 isozymes are modulated by dietary lipid in a selective manner; the levels of hepatic P450s 1A2, 2B2, 2E1, and 3A were regulated positively but the level of pulmonary P450 2B1 was suppressed by dietary lipid. PMID- 1632813 TI - Metabolic activation of lidocaine and covalent binding to rat liver microsomal protein. AB - Incubation of [14C]lidocaine with rat liver microsomes in the presence of an NADPH-generating system resulted in covalent bindings of a 14C-labelled material to microsomal protein. The covalent binding of radioactivity needed NADPH and atmospheric oxygen, and was diminished by purging of carbon monoxide and the addition of SKF-525A. Hence the covalent binding of a 14C-labelled material resulting from a reactive metabolite of lidocaine formed by cytochrome P450 dependent monooxygenation. The covalent binding measured at various concentrations of lidocaine (2.5-30 microM) followed Michaelis-Menten kinetics, and the Km value (4.52 microM) of the activation reaction was close to the Km value (1.78 microM) of lidocaine 3-hydroxylation. The metabolism-dependent covalent binding of lidocaine to microsomal protein as well as lidocaine 3 hydroxylase activity was much lower in the Dark Agouti strain rat, which is known as a poor-metabolizer animal model of debrisoquine 4-hydroxylation, than in the Wistar rat for the corresponding sexes. The covalent binding in male rats was greater than that in females of both strains, but the extent of the sex difference in the binding was smaller than that of the lidocaine N-deethylase activity in Wistar rats. Propranolol and quinidine, specific inhibitors of debrisoquine 4-hydroxylase, markedly inhibited lidocaine 3-hydroxylase activity of Wistar male rats, but not N-deethylase activity. These compounds also inhibited the metabolism-dependent covalent binding of lidocaine to microsomal protein. These strain difference and inhibition studies showed that the reaction converting lidocaine to a reactive metabolite capable of binding covalently to microsomal protein was related to lidocaine 3-hydroxylation, and may be catalysed by cytochrome P450 isozyme(s) belonging to the CYP2D subfamily. The covalent binding of radioactivity to rat liver microsomal protein was diminished by nucleophiles, reduced glutathione and cysteine, indicating that the reactive metabolic intermediate of lidocaine is an electrophilic metabolite such as an arene oxide. PMID- 1632814 TI - Interactions of amiodarone with model membranes and amiodarone-photoinduced peroxidation of lipids. AB - The potent antiarrhythmic drug, amiodarone (AMIO) exhibits phototoxicity, which is thought to be related to its interaction with biological membranes. We report here a spectroscopic study of the interactions of this drug with phosphatidylglycerol (PG) and phosphatidylcholine (PC) liposomes used as membrane model systems. A linear increase in absorbance at 300 nm was observed with increasing addition of AMIO to dimyristoyl-DL-PC (DMPC) liposomes over all the drugs-lipid molar ratio (Ri)s tested. In contrast, in the dimyristoyl-DL-PG (DMPG) liposomes, there was a dramatic increase in absorbance at values of Ri above unity. Light scattering by DMPG liposomes at 350 nm increased with increasing AMIO concentration up to a Ri = 1, and then decreased with increasing drug concentration. Such changes were not observed with the DMPC liposomes. Moreover, addition of AMIO changed the fluorescence polarization rate of 1,6 diphenyl 1,3,5-hexatriene embedded in these liposomes. It reduced the rate below the phase transition temperature (Tt) of the lipid, but increased it above this temperature. These effects on the lipidic phases observed at low Ri were more pronounced on the DMPG than on the DMPC liposomes. The strong interactions of AMIO with phospholipids, especially the acidic ones, were confirmed by liposome size determinations. All these data strongly suggest that the drug was incorporated in the core of the lipid bilayers. Such a penetration would favor a drug-photoinduced peroxidation of lipids. Indeed, UV irradiation of AMIO-DOPG mixtures led to the disappearance of the unsaturated fatty acids of phospholipids, checked by gas chromatography measurements, which was correlated with the amount of oxygen consumed. This showed that AMIO did photosensitize phospholipid peroxidation. PMID- 1632815 TI - Transport of sulfonated tetraphenylporphine by lipoproteins in the hamster. AB - We have examined the transport and distribution properties of a bisulfonated tetraphenylporphine (TPPS-2A), an amphiphilic photosensitizer that spontaneously associates to lipoproteins. At different times after intravenous injection of TPPS-2A in hamsters, plasma was fractionated by density ultracentrifugation and porphyrin concentrations were measured in the different plasma (lipo)protein fractions. In order to mimic human lipoprotein composition hamsters were preinjected with 23 mg of apolipoprotein/kg human low density lipoprotein. In addition, the whole body distribution is described as detected by a novel method for the tissue quantification of TPPS-2A. At 5 min after injection into the penile vein, more than 50% of the injected dose appears to be associated with lung tissue, while only 30% is present in plasma and bound exclusively to plasma lipoproteins. After the initial phase, a more retarded decrease in plasma porphyrin concentration is observed. Between 5 min and 6 hr after administration, a redistribution of TPPS-2A from the lungs to the liver takes place. It is concluded that in the hamster, an animal model representing human lipoprotein composition, TPPS-2A is transported essentially exclusively by plasma lipoproteins. No depletion or accumulation of TPPS-2A in a particular plasma lipoprotein fraction could be observed, suggesting a continuous redistribution of the compound. The molecular skeleton of TPPS-2A may serve as a model for the development of new drugs that either have improved in vivo properties due to transport by lipoproteins or have a beneficial effect on the lipoprotein particle itself. PMID- 1632816 TI - Thermodynamics of the anthracycline-nuclei interactions in drug-resistant and drug-sensitive K562 cells. AB - Fluorescence emission spectra from anthracycline-treated cells suspended in buffer have been used to measure the uptake of three anthracycline derivatives: Adriamycin (ADR), 4'-o-tetrahydropyranyl-Adriamycin (THP-ADR) and aclacinomycin (ACM) in drug-sensitive and drug-resistant K562 cells. The concentration of drug bound to the nucleus and free in the cytoplasm, at steady state, as well as the concentration of drug bound to the nucleus at equilibrium state have been determined at temperatures ranging from 6 degrees to 40 degrees. The enthalpies for the binding of ADR, THP-ADR and ACM to nuclei equal -35 +/- 3, -35 +/- 3 and 30 +/- 3 kJ/mol, respectively. These values compare with the enthalpies of binding of these drugs to naked DNA. PMID- 1632817 TI - Relationships between the aqueous chemistry and the in vitro cytotoxic activities of mixed-amine cisplatin analogues. AB - The possibility that variations in the cytotoxic activities of cisplatin analogues could be a result of differences in the aqueous chemistry of the compounds was investigated. A series of structurally related mixed-amine dichloroplatinum complexes (cis-coordinated with amine and various diphenylmethylamines and 1,2-diphenylethylamines) was prepared and selected physicochemical properties of the new compounds were characterized. Cytotoxicity was determined in two human breast cancer cell lines (MDA-MB-231 and MCF-7) and one human ovarian cancer cell line (SK-OV-3) by means of a microtiter assay. There is no apparent relationship between the hydrophobicities of the compounds and their cytotoxic potencies. There is no evidence for an inverse relationship between the aqueous stability of the dichloroplatinum complexes and cytotoxic potency, as has been reported for nitrogen mustards and some nitrosoureas. The differences in cytotoxic activity cannot be explained by inter-compound variations in the area under the concentration-time curves (AUC) of the dichloroplatinum complexes in culture medium. Thus, it appears that the differences in the cytotoxic potencies of this series of cisplatin analogues are related to factors other than dissimilarities in these physiochemical properties. Nevertheless, a relationship was found between the AUC of a dichloroplatinum complex in medium and the efficacy of the compound in the MCF-7 cell line. However, the AUC-efficacy relationship does not always hold in the MDA-MB-231 and SK-OV-3 cell lines. In these cells, treatment with a "high" bolus dose of platinum complex over finite exposure times is often less cytotoxic than treatment with lower doses of the same compound but over a continuous exposure time, although the cells are subjected to the same AUC of dichloroplatinum complex. PMID- 1632819 TI - Covalent binding of morphine to isolated rat hepatocytes. AB - Incubation of [3H]morphine with isolated hepatocytes caused covalent binding of [3H]-morphine to hepatocellular proteins. Sulfhydryl compounds protected against morphine-induced toxicity and decreased covalent binding. Analysis of covalently bound proteins in the cytosol by electrophoresis indicated that covalently bound radiolabel was associated with macromolecules greater than 25 kDa and increased throughout the incubation. In contrast, covalent binding to the particulate fraction was highly selectively associated with three protein bands of 50-53 and 33 kDa. Covalent binding of morphine to particulate fraction proteins was observed in hepatocytes which exhibited cellular damage. We conclude that the covalent binding of morphine to protein is associated with morphine-induced cytotoxicity. PMID- 1632818 TI - Microsomal lauric acid hydroxylase activities after treatment of rats with three classical cytochrome P450 inducers and peroxisome proliferating compounds. AB - In order to investigate a proposed relationship between induction of hepatic microsomal lauric acid hydroxylase activity and peroxisome proliferation in the liver, male Wistar rats were treated with peroxisome proliferating compounds, and the lauric acid hydroxylase activity, the immunochemical detectable levels of cytochrome P450 4A1 and the activities of peroxisomal enzymes were determined. In addition, the levels of cytochrome P450 4A1 and lauric acid hydroxylase activities were studied after treatment of rats with three cytochrome P450 inducers. After treatment with aroclor-1254, phenobarbital or 3 methylcholanthrene total cytochrome P450 was 1.7-2.7 times induced. However, no induction of lauric acid omega-hydroxylase activities or P450 4A1 levels were found. After treatment of rats with di(2-ethylhexyl)phthalate (DEHP) a dose dependent induction of lauric acid omega-hydroxylase activities, levels of cytochrome P450 4A1 and peroxisomal fatty acid beta-oxidation was found. Even at a dose-level of 100 mg DEPH/kg body weight per day a significant induction of these activities was observed. The main metabolites of DEHP, mono(2 ethylhexyl)phthalate and 2-ethyl-1-hexanol, also caused an induction of levels of P450 4A1, lauric acid omega-hydroxylase activities and the activity of peroxisomal palmitoyl-CoA oxidase. 2-Ethyl-1-hexanoic acid did not influence lauric acid omega-hydroxylase activities, but did induce levels of P450 4A1 and palmitoyl-CoA oxidase activities. Three other compounds (perfluoro-octanoic acid, valproate and nafenopin) induced both lauric acid omega-hydroxylase activity and peroxisomal palmitoyl-CoA oxidase activity. The plasticizer, di(2 ethylhexyl)adipate, did not induce levels of P450 4A1, lauric acid omega hydroxylase activities or palmitoyl-CoA oxidase activities. With the compounds tested a close association between the induction of lauric acid omega-hydroxylase activities and peroxisomal palmitoyl-CoA oxidase activity was found. These data support the theory that peroxisome proliferating compounds do induce lauric acid omega-hydroxylase activities and that there might be a mechanistic inter relationship between peroxisome proliferation and induction of lauric acid omega hydroxylase activities. PMID- 1632820 TI - Dolastatin 15, a potent antimitotic depsipeptide derived from Dolabella auricularia. Interaction with tubulin and effects of cellular microtubules. AB - Dolastatin 15, a seven-subunit depsipeptide derived from Dolabella auricularia, is a potent antimitotic agent structurally related to the antitubulin agent dolastatin 10, a five-subunit peptide obtained from the same organism. We have compared dolastatin 15 with dolastatin 10 for its effects on cells grown in culture and on biochemical properties of tubulin. The IC50 values for cell growth were obtained for dolastatin 15 with L1210 murine leukemia cells, human Burkitt lymphoma cells, and Chinese hamster ovary (CHO) cells (3, 3, and 5 nM with the three cell lines, respectively). For dolastatin 10, IC50 values of 0.4 and 0.5 nM were obtained with the L1210 and CHO cells, respectively. At toxic concentrations dolastatin 15 caused the leukemia and lymphoma cells to arrest in mitosis. In the CHO cells both dolastatin 15 and dolastatin 10 caused moderate loss of microtubules at the IC50 values and complete disappearance of microtubules at concentrations 10-fold higher. Despite its potency and the loss of microtubules in treated cells, the interaction of dolastatin 15 with tubulin in vitro was weak. Its IC50 value for inhibition of glutamate-induced polymerization of tubulin was 23 microM, as compared to values of 1.2 microM for dolastatin 10 and 1.5 microM for vinblastine. Dolastatin 10 noncompetitively inhibits the binding of vincristine to tubulin, inhibits nucleotide exchange, stabilizes the colchicine binding activity of tubulin, and inhibits tubulin-dependent GTP hydrolysis (Bai et al., Biochem Pharmacol 39: 1941-1949, 1990; Bai et al. J Biol Chem 265: 17141-17149, 1990). Only the latter reaction was inhibited by dolastatin 15. Nevertheless, its structural similarity to dolastatin 10 indicates that dolastatin 15 may bind weakly in the "vinca domain" of tubulin (a region of the protein we postulate to be physically close to but not identical with the specific binding site of vinca alkaloids and maytansinoids), presumably in the same site as dolastatin 10 (the "peptide site"). PMID- 1632821 TI - Investigation of the mechanism by which cyclophosphamide alters cytochrome P450 in male rats. AB - The effects of administration of the cytotoxic agent cyclophosphamide on cytochrome P450 have been examined in the liver microsomes of male rats. Microsomes were prepared after cyclophosphamide administration 1, 4 or 7 days prior to killing. The coadministration of cyclophosphamide with N-acetylcysteine has also been investigated. The microsomes were assayed for NADPH cytochrome P450 reductase, aminopyrine demethylase, erythromycin demethylase and androstenedione hydroxylase activities. Activities were generally unchanged 1 and 4 days after cyclophosphamide administration and were significantly decreased at 7 days. N Acetylcysteine did not alter the effects of cyclophosphamide at 7 days. The effect of cyclophosphamide in vitro has also been examined. Microsomes from untreated animals were subjected to the above assays following in vitro metabolic activation of cyclophosphamide in a reconstituted system in the presence and absence of N-acetylcysteine. All enzyme activities were significantly reduced by the cyclophosphamide metabolites. The presence of N-acetylcysteine prevented this inactivation. The results of these investigations suggest that cyclophosphamide inactivates hepatic cytochrome P450 in vitro and in vivo via different mechanisms. PMID- 1632822 TI - Immobilization of solubilized UDP-glucuronosyltransferase from rat liver microsomes to Sepharose 4B. AB - A method for the covalent binding of rat liver UDP-glucuronosyltransferase to a cyanogen bromide-activated agarose matrix is described. The rat liver microsomal fraction was solubilized with 8 mM 3-[(3-cholamidopropyl)dimethylammonio]-1 propanesulfonate (CHAPS); 90% of the microsomal protein was solubilized. Some 50 60% of this protein became bound covalently to the activated agarose matrix. The immobilized UPD-glucuronosyltransferase remained completely active for 50 days when stored at 4 degrees in a 20% (v/v) glycerol buffer (pH 7.4). The immobilized enzyme has a temperature optimum around 37 degrees, and a broad pH optimum (pH 5 7.4). The enzyme displayed linear kinetics over a period of 1 hr; it conjugates a large variety of substrates. PMID- 1632823 TI - Effects of chronic ethanol feeding on rat liver mitochondrial energy metabolism. AB - Chronic alcohol consumption is known to decrease hepatic mitochondrial respiration rate. It was shown here that the proton leak through the mitochondrial inner membrane was unaffected by chronic ethanol treatment. This indicates that changes in proton leak are not responsible for the alterations in respiration found in mitochondria isolated from ethanol-treated rats. Therefore, the lowered coupled respiration rate is solely due to a decrease in the activity of the electron transport chain. However, this alteration was only evident in coupled respiration (i.e. state 4) and was not apparent in uncoupled respiration. Thus, chronic ethanol treatment decreases the activity of the mitochondrial electron transport chain components which have control over coupled, but not uncoupled, respiration. Mitochondrial energy metabolism is regulated by thyroid hormone status. It was shown that the chronic alcohol treatment did not affect the circulating levels of thyroxine. Furthermore, the activity of mitochondrial alpha-glycerophosphate dehydrogenase, which is strongly affected by thyroid hormones, was unaltered by alcohol treatment. Thus, the effects of ethanol treatment on mitochondria occur independently of changes in circulating thyroid hormone levels. PMID- 1632824 TI - GABA in pancreatic islets: metabolism and function. PMID- 1632825 TI - Differential effects of cisplatin on the expression of chimeric marker genes in CV-1 cells. AB - The effect of the antitumor drug cisplatin on marker gene expression in CV-1 monkey cells was measured. When non-replicating test genes were introduced by transient transfection, there was strong differential inhibition caused by the drug. Expression of certain genes was relatively insensitive, but expression of others was inhibited as strongly as was DNA replication. Stronger promoters led to stronger inhibition. This selective inhibition was not observed with the pharmacologically inactive isomer transplatin. The results raise the possibility that inhibition of strongly expressed genes by cisplatin may contribute to the antitumor activity of the drug. PMID- 1632826 TI - Chronic physical activity: hepatic hypertrophy and increased total biotransformation enzyme activity. AB - Does chronic voluntary physical activity alter hepatic or intestinal capacities for xenobiotic biotransformation? This question was investigated by comparing biotransformation enzyme activities in liver and small intestine of active and sedentary rats. Male rats allowed unlimited access to a running wheel and fed ad lib. for 6 weeks were weight-matched to sedentary controls; the active rats ate 22% more food than the sedentary rats (P less than 0.05). Active rats ran 2.8 +/- 0.6 miles/day. Liver weights were higher in the active rats (11.2 +/- 0.2 vs 9.8 +/- 0.2 g; P less than 0.05), as were total liver protein, and liver microsomal and cytosolic protein (P less than 0.05). As a result of liver hypertrophy, the active rats showed higher total liver activity of several biotransformation enzymes, including 2-naphthol sulfotransferase, styrene oxide hydrolase, benzphetamine N-demethylase, ethacrynic acid glutathione S-transferase and morphine UDP-glucuronosyltransferase (P less than 0.05). In contrast, there was no detectable difference in total liver N-acetyltransferase activity toward p aminobenzoic acid, 2-naphthylamine, and 2-amino-fluorene as well as, relative hepatic enzyme activity (expressed per g liver or per mg protein) and total and relative intestinal enzyme activity. We conclude that chronic voluntary physical activity, accompanied by an increased food intake, results in liver hypertrophy and potentially increases total hepatic capacity to biotransform certain xenobiotic chemicals. PMID- 1632827 TI - Acetaminophen-induced depletion of glutathione and cysteine in the aging mouse kidney. AB - Glutathione (GSH) plays an essential role in the detoxification of acetaminophen (APAP) and the prevention of APAP-induced toxicity in the kidney. Our previous results demonstrated that a GSH deficiency is a general property of aging tissues, including the kidney, suggesting a hypothesis that senescent organisms are at greater risk to APAP-induced renal damage. To test this, C57BL/6NIA mice of different ages through the life span were injected with various doses of APAP, and the extent of GSH and cysteine (Cys) depletion and recovery were determined. At time intervals up to 24 hr, kidney cortex samples were obtained, processed and analyzed for glutathione status, namely GSH, glutathione disulfide (GSSG), Cys and cystine, using an HPLC method with dual electrochemical detection. In the uninjected controls, GSH and Cys concentrations decreased about 30% in the aging mouse, but the GSSG and cystine levels were unchanged during the life span. APAP administration depleted the kidney GSH and Cys contents in a dose- and time dependent manner. Four hours after APAP administration, GSH levels of the young, growing (3- to 6-month) and the mature (12-month) mice decreased 34 and 58%, respectively, and recovered to near control values by 24 hr (95 and 98%). In contrast, the extent of depletion in old (31-month) mice was greater (64%) and the 24-hr recovery was less, returning only to 56%. Likewise, Cys levels of the young and mature mice decreased 49 and 65%, respectively, 4 hr following APAP, and increased to 99 and 85% by 24 hr. In contrast, in old mice, there was a 78% depletion after 4 hr followed by a recovery of only 65% by 24 hr. These results demonstrated clearly that in the aging mouse kidney, a GSH and Cys deficiency occurs that is accompanied by an impaired APAP detoxification capacity. PMID- 1632828 TI - Effects of interleukin-6 on cytochrome P450-dependent mixed-function oxidases in the rat. AB - Intravenous treatment of male rats with recombinant human interleukin-6 (rhIL6) at 50, 100 and 200 micrograms/kg (corresponding to 4, 8 and 16 x 10(4) U/animal, respectively) reduced the activities of hepatic microsomal cytochrome P450 dependent monoxygenases to varying degrees. Ethylmorphine-N-demethylase activity fell to 53% of control values, an effect similar to that induced by 2.5 mg/kg Escherichia coli lipopolysaccharide (LPS). Ethoxycoumarin-O-deethylase activity was also sensitive to inhibition, whereas IL6 had little effect on the activities of other P450-dependent enzymes, including ethoxyresorufin-O-deethylase. Pentoxyresorufin dealkylase activity, which is representative of the cytochrome P450 IIB 1/2 subfamily, was unaffected by IL6 whereas LPS reduced it to 33.7% of control values. Another hepatocyte-related parameter, serum concentration of alpha 1-acid glycoprotein (AGP), was increased by up to 3.5-fold over baseline by IL6 and 10-fold by LPS. Recombinant human interleukin-1 beta (rhIL1 beta) (10 micrograms/kg, corresponding to 5 x 10(4) U/rat) and recombinant human tumor necrosis factor alpha (rhTNF) (150 micrograms/kg corresponding to 24 x 10(4) U/rat) were both as potent as LPS (2.5 mg/kg) in increasing serum AGP levels and reducing hepatic microsomal monoxygenase activities. IL6 did not potentiate the effects of rhIL1 beta. Hepatic microsomal glucuronyltransferase activities were little affected by LPS and unaffected by rhIL6. Finally, rhIL6 was more potent after i.p. injection than after i.v. or s.c. injection. These results suggest that the effects of LPS, TNF and IL1 on the mixed-function oxidase system in vivo may be due partly to an induction of IL6 in vivo. The different sensitivities of the enzymes to IL6 but not to IL1 or TNF may be due to the involvement of two distinct mechanisms. PMID- 1632829 TI - New isoflavonoids as inhibitors of porcine 5-lipoxygenase. AB - The inhibitory activity of new isoflavonoids on 5-lipoxygenase of porcine leukocytes was investigated. Isoflavans (I) proved to be stronger inhibitors than isoflavones (II). The isoflavans containing ortho-hydroxy groups in ring A showed the lowest Ki values (0.8-50 microM). In comparison, isoflavans with meta dihydroxy groups exhibited Ki values higher than 150 microM. The effect of commercial antioxidants was tested also on porcine 5-lipoxygenase. Butylated hydroxyanisole (Ki: 25 microM) and butylated hydroxytoluene (Ki: 55 microM) revealed moderate inhibitory activity, whereas L-ascorbic acid, L-ascorbyl palmitate, dl-alpha-tocopherol and n-propyl gallate showed weak inhibitory activities (Ki: 100-260 microM). PMID- 1632830 TI - The toxicological relevance of paracetamol-induced inhibition of hepatic respiration and ATP depletion. AB - In order to elucidate the role of mitochondrial dysfunction in paracetamol induced hepatotoxicity, the effects of paracetamol on the oxygen consumption and ATP content of the isolated perfused rat liver were correlated with parameters of hepatic viability and hepatotoxicity. Paracetamol at 5 g/L reduced the oxygen consumption of the livers by about 80% and hepatic ATP content by 96%. Hepatotoxicity was evident from the nearly complete interruption of bile secretion, a marked release of enzymes [glutamate-pyruvate transaminase (GPT), lactate dehydrogenase (LDH)] in the perfusate, a depletion of hepatic glutathione and an accumulation of calcium in the liver. Paracetamol-induced hepatotoxicity could be prevented completely by using livers from non-fasted rats as well as by addition of fructose to the perfusate of livers from fasted animals. Both treatments resulted in an increased energy supply from anaerobic glycolysis as evidenced by a large release of lactate and pyruvate into the perfusate, but did not inhibit paracetamol-induced decline of oxygen consumption. The decrease in hepatic oxygen consumption depended on the dose of paracetamol and occurred first at a concentration of 0.2 g/L (-10%). LDH and GPT release, on the other hand, was elevated at 2 and 5 g/L and calcium accumulation occurred at 5 g/L paracetamol only. Inhibition of mixed-function oxidases by dithiocarb did not prevent the decrease in oxygen consumption and the resulting hepatic injury induced by paracetamol. The oral administration of the high dose of 5 g/kg paracetamol in vivo to rats exerted strong hepatotoxicity but produced maximal serum levels of 800 mg/L paracetamol only and did not decrease hepatic oxygen consumption as measured in vitro. Our results show that in the isolated perfused rat liver in vitro, only high concentrations of paracetamol can produce "chemical hypoxia" by attacking mitochondria so as to cause hepatic injury. Such high concentrations of paracetamol are not attained in vivo, however. "Chemical hypoxia", thus, seems not to be relevant to the well-known hepatotoxic action of paracetamol. PMID- 1632831 TI - Monoclonal antibodies distinguish between carboxylesterase isoenzymes in different tissues of rat and guinea pig. AB - The carboxylesterase (CarbE) activity in the main tissues (lung, liver, plasma and small intestine) of both the rat and guinea pig was separated by chromatofocusing. The three CarbE isoenzymes in the small intestine from both species showed nearly identical pI values. Monoclonal antibodies (MAbs) raised against rat lung CarbE (pI 5.8) were used in enzyme-linked immunosorbent assays to distinguish between these closely related CarbE isoenzymes. None of the MAbs did bind to the active site as no inhibition of the enzyme was seen when the MAbs were added. The immunological study showed a strong relationship between lung CarbE (pI 5.8) and the rat liver CarbE (pI 6.0). The MAbs were also strongly bound to the high pI forms of the CarbE isoenzymes in plasma and small intestine from both rat and guinea pig, but not with the low pI forms. These results indicate that two immunochemically distinct categories of CarbE isoenzymes are present in the plasma and small intestine. PMID- 1632832 TI - Synergism in insulin-like effects of molybdate plus H2O2 or tungstate plus H2O2 on glucose transport by isolated rat adipocytes. AB - The effect of molybdate, tungstate, molybdate plus H2O2 or tungstate plus H2O2 on 3-O-methylglucose (3-O-MG) uptake was studied in isolated rat adipocytes to investigate whether these agents possess an insulin-like action. High concentrations (10-30 mM) of molybdate or tungstate significantly stimulated the uptake of 3-O-MG while 1 mM of the metaloxides did not. The combination of 1 mM molybdate and 1 mM H2O2, or 1 mM tungstate and 1 mM H2O2 induced striking stimulation of the uptake of 3-O-MG in a synergistic manner, whereas 1 mM H2O2 alone showed only a small effect. The effect of metaloxides plus H2O2 (1 mM) and the effect of insulin (20 nM) were not additive, and both effects were ATP or energy dependent based on experiments using KCN. These results indicate that a weak insulin-like effect of molybdate or tungstate is potentiated synergistically with H2O2, presumably by producing peroxocompounds. Based on the present findings, these new agents may be useful for investigating the mechanism of insulin action and may indicate a new class of drugs for diabetes mellitus. PMID- 1632833 TI - Inhibition of transketolase and pyruvate decarboxylase by omeprazole. AB - Omeprazole inhibited two thiamin diphosphate-dependent enzymes, pyruvate decarboxylase (EC 4.1.1.1, PDC) from Zymomonas mobilis and transketolase (EC 2.2.1.1, TK) from human erythrocytes. Inhibition of PDC was competitive with the coenzyme with a Ki value of 42 +/- 3 microM, whereas inhibition of TK was complex. PMID- 1632834 TI - Detection of human lung cytochromes P450 that are immunochemically related to cytochrome P450IIE1 and cytochrome P450IIIA. AB - We have used monoclonal antibodies that were prepared against and specifically recognize human hepatic cytochromes P450 as probes for solid phase radioimmunoassay and Western immunoblotting to directly demonstrate the presence in human lung microsomes of cytochromes P450 immunochemically related to human liver cytochromes P450IIE1 (CYP2E1) and P450IIIA (CYP3A). The detected levels of these cytochromes are much lower than levels in human liver microsomes, but similar to the levels seen in microsomes from untreated baboon lung. Proteins immunochemically related to two other constitutive hepatic cytochromes P450, cytochrome P450IIC8 (CYP2C8) and cytochrome P450IIC9 (CYP2C9), were not detectable in lung microsomes. PMID- 1632835 TI - Stimulation of macrophage tumouricidal activity by 5,6-dimethyl-xanthenone-4 acetic acid, a potent analogue of the antitumour agent flavone-8-acetic acid. AB - The new antitumour drug 5,6-dimethylxanthenone-4-acetic acid (5,6-MeXAA; NSC 640488) was 14-fold more potent than the investigational chemotherapeutic drug flavone-8-acetic acid (NSC 347512) in stimulating tumouricidal activity in cultures of resident murine peritoneal macrophages. The tumouricidal activity of thioglycollate-elicited and Bacillus Calmette-Guerin-primed macrophages was also significantly enhanced by 5,6-MeXAA. Stimulation of macrophage tumouricidal activity by 5,6-MeXAA was not affected by inhibitors of superoxide and nitric oxide production, but was reduced by cyclosporin A, an inhibitor of protein secretion. Inhibitors of neutral proteases had no effect. Cortisone, dexamethasone, indomethacin, dibutyryl cAMP, prostaglandin E2 and prostacyclin, but not prostaglandin F2 alpha, inhibited stimulation, suggesting the involvement of tumour necrosis factor-alpha (TNF). However, antibodies to TNF did not inhibit stimulation. The results suggest that 5,6-MeXAA acts on macrophages in a manner similar to that of endotoxin, utilizing a pathway which includes arachidonic acid metabolism and requiring cell-cell contact with target cells for a tumouricidal effect. PMID- 1632836 TI - Action of ebselen as an antioxidant against lipid peroxidation. AB - The action of ebselen (2-phenyl-1,2-benzoisoselenazol-3(2H)-one) as an antioxidant was studied under various conditions to clarify how it prevents oxidative damage. It did not react with diphenylpicrylhydrazyl nor did it suppress the oxidation of methyl linoleate in acetonitrile solution or in aqueous dispersions induced by free radical initiator, suggesting that ebselen does not act as a potent radical scavenging antioxidant. On the other hand, it suppressed the oxidation of methyl linoleate emulsions in aqueous dispersions induced by iron. It also suppressed the spontaneous oxidation of rat brain and liver homogenates, but it did not suppress the oxidation of these homogenates induced by a free radical initiator. It was also found that ebselen reduced the fatty acid hydroperoxides to their corresponding alcohols and this reaction was enhanced by the presence of glutathione. These results suggest that ebselen acts as an antioxidant by reducing hydroperoxides, but that it does not act as a radical-scavenging antioxidant. PMID- 1632838 TI - Altered regulation of Cyp1a-1 gene expression during cultivation of mouse hepatocytes in primary culture. AB - Alterations in Cyp1a-1 gene expression in adult C57BL/6 mouse hepatocytes were followed after transferring them to primary culture during the initial 5 days. Changing the medium to a fresh one was associated with considerable amounts of Cyp1a-1 gene mRNA with a peak at around 6 hr after the medium change, followed by a decrease to negligible levels 24 hr later. Treatment of hepatocytes with cycloheximide increased the medium change-associated mRNA expression, the levels being equivalent to those observed after treatment with 3.2-25.6 nM 3 methylcholanthrene plus cycloheximide. With increasing length of culture period, cycloheximide-aided enhancement of the medium change-associated mRNA transcription increased. Although the chemical alone did not induce Cyp1a-1 gene transcripts in hepatocytes at day 1 or 2 of cultivation, for which medium had been changed 24 hr previously, prominent induction of transcripts was evident at later periods, the levels being elevated in accordance with length of time in culture. To examine whether or not the mRNA transcribed under these culture conditions was translatable, the cells were treated with actinomycin D after washing out the cycloheximide, in order to inhibit degradation of the generated mRNA (Nemoto N and Sakurai J, Carcinogenesis 12: 2115-2121, 1991). After these procedures significant elevation of aryl hydrocarbon hydroxylase activity was observed in hepatocytes, the rise being well correlated with elevated levels of mRNA transcripts. The observations suggest that the Cyp1a-1 gene might be expressed at low levels during the initial phase of cultivation of mouse hepatocytes in primary culture. Whether this expression might be essential for mouse hepatocytes to adapt to culture conditions is unclear. The findings do suggest, however, that superinducibility of the gene expression after cycloheximide treatment might be a result of a regulatory mechanism operating after adaptation to culture. PMID- 1632837 TI - Biscoclaurine alkaloids inhibit receptor-mediated phospholipase A2 activation probably through uncoupling of a GTP-binding protein from the enzyme in rat peritoneal mast cells. AB - The mechanism underlying the inhibitory effect of biscoclaurine (bisbenzylisoquinoline) alkaloids on phospholipase A2 activation in the signalling system of stimulated rat peritoneal mast cells was studied. Cepharanthine, berbamine and isotetrandrine inhibited antigen- and compound 48/80 induced arachidonic acid liberation, but not diacylglycerol formation or histamine release. They had no effect on A23187-induced arachidonic acid liberation, which was prevented by p-bromophenacyl bromide, a known phospholipase A2 inhibitor, and also did not affect phospholipase A2 activity in a cell-free system including an exogenous phospholipid substrate. Each alkaloid also inhibited arachidonic acid liberation induced by guanosine 5'-O-(3 thiotriphosphate) in saponin-permeabilized mast cells, and by mastoparan or NaF plus AlCl3 intact cells. Furthermore, each alkaloid abolished the inhibitory effect of islet-activating protein on the compound 48/80-induced arachidonic acid liberation. These data suggest that these alkaloids suppress the receptor mediated phospholipase A2 activation through, at least in part, uncoupling of a GTP-binding protein from the enzyme, rather than by affecting the enzyme directly. PMID- 1632839 TI - The cytotoxicity, DNA crosslinking ability and DNA sequence selectivity of the aniline mustards melphalan, chlorambucil and 4-[bis(2-chloroethyl)amino] benzoic acid. AB - Three aniline derivatives melphalan (L-PAM), chlorambucil (CHL) and 4-[bis(2 chloroethyl)amino] benzoic acid (BAM) have been compared on the basis of their in vitro cytotoxicities, DNA interstrand crosslinking ability and DNA sequence selectivity. Cytotoxicity was assessed in the human colonic adenocarcinoma LS174T and leukaemic K562 cell lines using the sulpho-rhodamine B and tetrazolium dye reduction assays. The order of cytotoxicities was L-PAM greater than CHL greater than BAM in both cell lines with K562 being less sensitive than LS174T. This was different from the order CHL greater than L-PAM greater than BAM which would be predicted from simple chemical reactivity or rate of hydrolysis, parameters which have been used previously as indicators of biological potency for aromatic nitrogen mustards. DNA interstrand crosslinking in cells as determined by alkaline elution showed a correlation with IC50 values. The ranking order of activity was further predicted by the ability of the agents to produce interstrand crosslinks in isolated DNA. The extent of guanine N-7 alkylation, assessed using a modified DNA sequencing technique, mirrored cytotoxicity and crosslinking ability, but at equivalent levels of alkylation there was no significant difference in DNA sequence selectivity. These data demonstrates that simple chemical reactivity or hydrolysis rate is not a good indicator of DNA reactivity or cytotoxicity for a number of aniline mustards, whereas DNA interstrand crosslinking ability either measured directly in cells or in isolated DNA, gives a good indication of biological activity. PMID- 1632840 TI - Substoichiometric inhibition of microtubule formation by acetaldehyde-tubulin adducts. AB - We have shown previously that acetaldehyde forms stable covalent adducts with tubulin, resulting in impaired microtubule formation. The present study explored the mechanism responsible for impaired microtubule formation caused by the substoichiometric stable binding of acetaldehyde to tubulin. The free tubulin dimer was much more reactive with acetaldehyde than microtubules, binding more than twice as much aldehyde. The dimer also formed nearly twice as many stable adducts on its alpha-chain as on its beta-chain, whereas microtubules exhibited an equal distribution of adducts between the two subunits. These data confirm that the alpha-chain of free tubulin, but not microtubules, has an accessible highly reactive lysine (HRL) residue that is a preferential target of acetaldehyde binding. Adduct formation with the HRL residue also correlated with impaired tubulin polymerization, and only 0.08 moles of acetaldehyde bound per mole of HRL was required for complete inhibition; however, adducts with other lysine residues (bulk adducts) did not affect assembly. Adducts to microtubule associated proteins (MAPs) also impaired the assembly of tubulin, but were much less effective than HRL adducts. In a copolymerization assay, HRL-adducted tubulin, in addition to being itself assembly incompetent, also interfered with polymerization of normal (unadducted) tubulin. Bulk adducts did not alter assembly and were incorporated normally into the growing polymer. When tubulin was cleaved by the proteolytic enzyme, subtilisin, microtubule formation could readily take place in the absence of MAPs. In this polymerization system, HRL adducts, but not bulk adducts, still markedly inhibited assembly. When low concentrations of acetaldehyde (50 microM) were used to generate HRL adducts, an adduct on only 1 out of 20 tubulin molecules was sufficient to totally block polymerization. These findings indicate that substoichiometric amounts of acetaldehyde bound to HRL of tubulin can markedly inhibit microtubule formation via direct interference of dimer-dimer interactions, and further suggest that low concentrations of acetaldehyde could generate sufficient amounts of HRL adducts in cellular systems to alter microtubule formation and function. PMID- 1632841 TI - Ethanol metabolism in rat brain homogenates by a catalase-H2O2 system. AB - Homogenates of perfused rat brains incubated in the presence of ethanol (50-100 mM) and glucose (10 mM) were found to oxidize ethanol to acetaldehyde. The addition of glucose oxidase, a known hydrogen peroxide generator, to the incubation medium, significantly (P less than 0.05) increased the generation of acetaldehyde. The presence in the incubation medium of metyrapone, an inhibitor of cytochrome P450, or pyrazole, an alcohol dehydrogenase inhibitor, did not affect the levels of acetaldehyde obtained. Conversely, the presence of 3-amino 1,2,4-triazole, a known catalase inhibitor, induced a concentration-dependent reduction of the amount of acetaldehyde generated after incubation, even in the presence of glucose oxidase. Homogenates of perfused brains of rats treated with 3-amino-1,2,4-triazole or cyanamide (another H2O2-dependent catalase blocker) also showed a dose-dependent reduction of the acetaldehyde obtained. These findings support the notion that a catalase-mediated oxidation of ethanol is present in rat brain homogenates. It is suggested that this local oxidation of ethanol may have important biological implications. The data of both studies increase support for the notion that acetaldehyde is produced directly in the brain and that it may be the agent mediating some of the psychopharmacological properties of ethanol and be one of the factors determining the propensity of an animal to voluntarily consume ethanol. PMID- 1632842 TI - Metabolism of 5-fluoro-dopa and 6-fluoro-dopa enantiomers in aggregating cell cultures of fetal rat brain. AB - The cerebral metabolism of enantiomers of 5-fluoro-DOPA (5F-DOPA) and 6-fluoro DOPA (6F-DOPA) was characterized in organotypic cell cultures of fetal rat brain. This system permits the investigation of metabolic processes in brain tissue exclusively, without the effects of peripheral metabolism and transport. Metabolic profiles for each substrate were determined in comparison with those of L-DOPA and D-DOPA. The uptake of DOPA and fluoro-DOPA in aggregating brain cell cultures is strongly preferential for L-enantiomers. Decarboxylation by aromatic L-amino acid decarboxylase is an active step: the major products are dopamine (DA) or 6F-DA and their corresponding products of oxidative deamination, i.e. dihydroxyphenylacetic acid (DOPAC) or 6F-DOPAC, respectively. Decarboxylation products of D-enantiomers occur in lower amounts, and 5F-D-DOPA is not decarboxylated. However, 5F-DOPA is O-methylated to a great extent, and levels of 3-O-methyl-5F-DOPA are higher after incubation with 5F-D-DOPA than with 5F-L DOPA. These data may serve as a support for more detailed modeling of [18F]F-DOPA metabolism than can be applied to the evaluation of the cerebral biochemistry of the DA system with positron emission tomography in vivo. PMID- 1632843 TI - Carotid stenosis is a powerful predictor of a positive exercise electrocardiogram in a large hyperlipidemic population. AB - Hypercholesterolemia is a major risk factor in coronary heart disease (CHD) and ischemic stroke. However, there is no general agreement on the usefulness of systematic screening of patients with hyperlipidemia by stress exercise electrocardiogram (ECG). The feasibility of this approach would depend on selecting patients with a high risk of CHD, since the sensitivity and specificity of the test depends on the prevalence of the disease. In view of the association of CHD and ischemic stroke, we undertook a study to determine whether the presence of atherosclerosis in the carotid arteries was predictive of a positive exercise ECG in a group of 778 asymptomatic patients referred to their hyperlipidemia. We a much higher percentage of positive exercise ECG in patients with carotid atherosclerosis in our ultrasonographic examinations. In a multiple regression analysis which included 13 parameters (age, sex, body mass index, arterial blood pressure, lipid parameters, serum level of glucose, smoking status and the severity of carotid lesions), the strongest predictors of a positive exercise ECG test were age (P = 0.014) and the degree of carotid atherosclerosis (P = 0.010). We therefore conclude that hyperlipidemic patients with atherosclerotic lesions on carotid arteries would benefit most from screening by the exercise ECG. PMID- 1632844 TI - U-73482: a novel ACAT inhibitor that elevates HDL-cholesterol, lowers plasma triglyceride and facilitates hepatic cholesterol mobilization in the rat. AB - U-73482, a novel acylCoA:cholesterol acyltransferase (ACAT) inhibitor with systemic activity, has been evaluated for its effects on a variety of lipid metabolic parameters in the rat. The compound inhibits ACAT in vitro in cultured Fu5AH rat hepatoma cells and demonstrates systemic activity through inhibition of hepatic ACAT in rats receiving the drug orally. U-73482 also lowers plasma triglycerides at 40 mg/kg per day in the rat and elevates high density lipoprotein cholesterol (HDL-chol) in a dose-related fashion over the range of daily intakes of 0-40 mg/kg in the rat. Elevations in HDL-chol are followed by elevations in total plasma cholesterol in normal rats but the compound exerts hypocholesterolemic activity in cholesterol-fed rats and promotes clearance of stored hepatic sterol in rats pretreated with a hypercholesterolemic diet and then changed over to normal chow. The triglyceride-lowering and HDL-chol elevating effects of U-73482 coupled with its ability to promote tissue sterol clearance and block the hypercholesterolemic effects of dietary cholesterol in animals, suggests that the compound has potential as a therapeutic agent for treatment of lipid disorders in man. PMID- 1632845 TI - Probucol and atherosclerosis in the Watanabe heritable hyperlipidemic rabbit- long-term antiatherogenic effect and effects on established plaques. AB - We performed two studies to investigate the effect of probucol on atherogenesis in vivo in the Watanabe heritable hyperlipidemic (WHHL) rabbit. In the first study (Study A), probucol was administered to 2-month-old WHHL rabbits, to evaluate its long-term effect. When killed at about 1.5 years of age, the percentage area of aorta covered with atherosclerotic plaque in probucol-treated rabbits was markedly less than that seen in non-treated rabbits (23.0 +/- 11.4% vs. 87.7 +/- 8.1%, M +/- S.D., P less than 0.001). In the second study (study B), administration of probucol was commenced with 8-month-old WHHL rabbits to investigate whether the drug was effective for limiting atherosclerosis in rabbits in which plaques had already developed. When killed after 6 months of treatment, the percentage area of aorta covered with plaque was 38.1 +/- 12.1% in treated rabbits and 82.7 +/- 22.6% in non-treated rabbits (P less than 0.02). Microscopic observations of lesions also supported the effect of probucol. Probucol treatment resulted in a change not only in the size but also the composition of lesions. Thus, probucol was effective in preventing atherosclerosis in long-term studies at both early and late stages. PMID- 1632846 TI - A prospective study of obesity, lipids, apolipoproteins and ischaemic heart disease in women. AB - The aim of the study was to examine the relationships of obesity, lipids and apolipoproteins with the risk for subsequent ischaemic heart disease in middle aged women, using a case-control study nested within a cohort study. A total of 3634 women aged 26-88 were recruited in Guernsey between 1977 and 1985 and followed until June 1986 by abstraction of their general practitioners' records. Fifty-one cases of incident ischaemic heart disease (11 myocardial infarction, 40 angina) were identified. For each case up to 4 controls were selected, matched for age and date at recruitment. Odds ratios for the development of ischaemic heart disease in the middle and upper thirds of the distribution for each variable in the controls, relative to the lowest third (and two-sided P-values for linear trends), were: 3.0, 2.6 (0.015) for Quetelet's index; 3.3, 5.1 (0.003) for total cholesterol; 0.5, 0.6 (0.102) for apolipoprotein A-I; 1.8, 2.4 (0.015) for apolipoprotein B; 1.3, 2.1 (0.155) for apolipoprotein(a). The increased risks associated with increased Quetelet's index and total cholesterol were independent of each other and these variables were more strongly related to myocardial infarction than to angina. The relationships of risk with serum cotinine, fatty acids, dehydroepiandrosterone sulphate and sex hormone binding globulin were weak and did not approach statistical significance. PMID- 1632847 TI - The oxidative modification of low density lipoprotein by human lymphocytes. AB - Oxidation of low density lipoprotein in atherosclerotic lesions may be involved in converting macrophages into lipid-laden foam cells. Lesions contain endothelial cells, smooth muscle cells, macrophages and lymphocytes. The first three types of cells have been shown previously to modify low density lipoprotein so as to increase its uptake by macrophages. We report here that lymphocytes from human blood are also capable of doing this. The modification process was an oxidative one because there was an increase in the thiobarbituric acid-reactive substances in media containing lymphocyte-modified low density lipoprotein and the modification could be inhibited by the antioxidants butylated hydroxytoluene and probucol. The lymphocyte-modified low density lipoprotein was taken up and degraded by macrophages by their scavenger receptor(s). PMID- 1632848 TI - Non-macrophage-related accumulation of cholesterol during probucol treatment in familial hypercholesterolemia: report of two cases. AB - Two patients receiving long-term (3-4 years) treatment with probucol for familial hypercholesterolemia (FH) developed diffuse yellow lesions over the upper eyelids suggesting lipid storage in those tissues (diffuse lipid-storage lesions). Interestingly, each patient had shown a substantial reduction in their cholesterol levels together with a marked regression of their tendon xanthomas or typical xanthelasmas during treatment. To evaluate the role of probucol in this unusual finding we conducted histological and immunochemical evaluations of the lesions (removed surgically) and compared them with those of a non-probucol treated subject with FH and typical audinal xanthelasma. In both probucol-treated patients the lesions were filled with foam cells and contained large amounts of cholesteryl ester. However, immunochemical analysis of the lesions of one patient using anti-monocyte monoclonal antibody (HAM56) demonstrated that they were not composed of macrophage-derived foam cells in contrast to those of the non probucol-treated subject which stained clearly with anti-monocyte monoclonal antibody. In each case the foam cells did not react with muscle-actin-specific monoclonal antibody (HHF35). It appears that non-macrophage-related diffuse lipid storage lesions may occur even during treatment with probucol despite the reduction in cholesterol levels and the regression of xanthomas, suggesting that probucol may alter the distribution of cholesterol from the macrophage to other cells. PMID- 1632849 TI - Interleukin 6 gene transcripts are expressed in atherosclerotic lesions of genetically hyperlipidemic rabbits. AB - We have investigated the involvement of interleukin 6 (IL-6), a growth-regulatory molecule for vascular smooth muscle cells (SMC), in the development of atherosclerotic lesions of Watanabe heritable hyperlipidemic (WHHL) rabbits. In in situ hybridization analysis, quite low levels of IL-6 mRNA were expressed in 'quiescent' SMC cultured from WHHL rabbits; however, high levels of IL-6 mRNA were induced in SMC exposed to 10% fetal bovine serum (FBS), suggesting that growth-stimulated SMC themselves can synthesize IL-6. In in vivo WHHL aortae, transcripts for the IL-6 gene were clearly observed in the fibrous plaques. These findings support the premise that IL-6 is an important autocrine and/or paracrine regulator of SMC proliferation and of pathogenesis of atherosclerosis in this animal model. PMID- 1632850 TI - Acid cholesteryl ester hydrolase activity of mononuclear leukocytes in patients with non-insulin-dependent diabetes mellitus: studies before and after treatment of diabetes. AB - The change of acid cholesteryl ester hydrolase activity in mononuclear leukocyte following treatment of diabetes mellitus was studied in 21 patients with non insulin-dependent diabetes mellitus (NIDDM). Enzyme activity before treatment in the patients was significantly lower than that in 14 age-matched healthy subjects (1.20 +/- 0.15; mean +/- S.E. vs. 2.20 +/- 0.17 nmol/mg protein/h, P less than 0.01). Enzyme activity before treatment in the patients was significantly increased (P less than 0.05) after 4-8 weeks of treatment. However, enzyme activity of 1.43 +/- 0.14 nmol/mg protein/h observed after treatment in the patients was significantly lower (P less than 0.01) than that in the healthy subjects. There was a significant negative correlation between enzyme activity before treatment and the increase in enzyme activity following treatment (rs = 0.555, P less than 0.01, n = 21). These results indicate that low level of enzyme activity may be insufficiently improved by the treatment of diabetes, and the risk for the development of atherosclerosis as viewed from the enzyme activity may persist even after the treatment in NIDDM. PMID- 1632851 TI - Familial defective apolipoprotein B100: clinical characteristics of 54 cases. AB - Familial defective apolipoprotein B100 (FDB) is a recently identified dominantly inherited genetic disorder, which is characterized by a decreased affinity of low density lipoprotein (LDL) for the LDL receptor. FDB is caused by a G to A mutation at nucleotide 10 708 in exon 26 of the apo B gene creating a substitution of glutamine for arginine in the codon for amino acid 3500. To determine the consequences of the arginine(3500)----glutamine mutation on plasma lipid levels and other clinical features, we have investigated 54 FDB heterozygotes from Germany (24 men, 30 women, mean age 37.2 (4-73) years). The average total cholesterol level in plasma was 308 mg/dl (average LDL-cholesterol 242 mg/dl), which was 116 mg/dl (120 mg/dl) above the 50th percentile of the age and sex-matched controls reported in the LRC population studies (Lipid Research Clinics' Program 1980). Tendon xanthoma and arcus lipoides were present in 25.9% and 22.2% of the patients, respectively. Plaques in the carotid arteries, determined by duplex scanning, were present in 38.9%, and coronary artery disease was present in 22.2%. This study shows that the combination of tendon xanthoma, arcus lipoides and premature atherosclerosis is no longer totally appropriate for the diagnosis of familial hypercholesterolemia (FH). It rather seems that these features are characteristic of a defective LDL receptor pathway, which could be caused by a defective LDL receptor or a defective ligand apo B100. The distinction between FH and FDB may have therapeutic implications, because certain lipid lowering drugs act by stimulation of the LDL receptor, which has a normal function in FDB. PMID- 1632852 TI - Effect of long-term insulin deficiency and insulin treatment on the composition of triglyceride-rich lipoproteins and triglyceride turnover in rats. AB - The effect of long-term (4 months) insulin deficiency on triglyceride turnover was examined using Triton WR1339 in rats. Triglyceride secretion rate was estimated in rats 2 weeks and 4 months after induction of diabetes with 40 mg/kg of streptozotocin. By the second week diabetic rats showed prominent hyperglycemia and the plasma insulin level was very low. In spite of a lower triglyceride secretion rate compared to non-diabetic control rats, diabetic rats showed normotriglyceridemia. Thus, the estimated fractional catabolic rate for plasma triglyceride was decreased in the diabetic rats of 2 weeks duration. By the fourth month diabetic rats still showed a suppressed triglyceride secretion rate but plasma triglyceride was markedly higher than in the non-diabetic control rats. Therefore, their estimated fractional catabolic rate for plasma triglyceride was severely suppressed. They also showed hyperglycemia and hypercholesterolemia. The triglyceride-rich lipoprotein particles obtained after Triton injection in long-term diabetic rats were significantly cholesterol enriched and triglyceride-depleted compared to control rats. These changes were already present in 2-week diabetic rats but the magnitude was significantly smaller that those in long-term diabetic rats. All of these abnormalities (including triglyceride turnover and the particle composition) were almost normalized by 2 weeks of insulin treatment (6 units/day). Thus, it was concluded from the present data that duration of insulin deficiency is an important determinant of triglyceride removal rate from the circulation in rats. Further modification of lipid composition of triglyceride-rich lipoprotein particles by long-term insulin-deficiency could be one of the reasons for this removal defect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632853 TI - Cellular damage in mouse peritoneal macrophages exposed to cholesteryl linoleate. AB - Mouse peritoneal macrophages readily oxidize cholesteryl linoleate/bovine serum albumin emulsions to produce soluble lipid oxidation products, some of the latter being thought to cause cell damage. Mouse peritoneal macrophages were therefore incubated in the presence of cholesteryl linoleate/bovine serum albumin emulsion with and without the addition of dl-alpha tocopherol. The macrophages were observed morphologically and cell damage was estimated by three methods: trypan blue exclusion, lactate dehydrogenase release and tritiated adenine release. All the methods showed significant cell damage which was reduced in the presence of physiological levels of dl-alpha tocopherol. Cholesteryl oleate/bovine serum albumin, which is taken up by macrophages but is not oxidized, was not toxic. dl Alpha tocopherol was itself toxic in higher concentrations. This self-inflicted macrophage damage might explain the onset of necrosis in atherosclerotic plaques. PMID- 1632854 TI - Low serum cholesterol, cancer and other noncardiovascular disorders. AB - There has been much concern and discussion whether reduction of serum cholesterol by diet or drugs, while preventing coronary heart disease, might cause an increase in the risk of dying from noncardiovascular disorders, in particular cancer. A review of the evidence from ecological, cross-cultural comparisons, prospective epidemiological cohort studies and intervention trials provides no indication for a cause-and-effect association between low serum cholesterol or serum cholesterol lowering and the risk of cancer, except possibly at very low levels. An inverse relationship between noncardiovascular-noncancer mortality and serum cholesterol level does exist but the link is unlikely to be causal; for better understanding, there is a need for studying the biological, lifestyle and social correlates of this association. Continuing observations should pay attention to the accuracy of information on specific causes of noncardiovascular deaths, especially mortality not due to disease. Further research needs to include investigations into the determinants of low serum cholesterol levels and their possible influence on biological functions. It is concluded that the current recommendations for coronary heart disease prevention, aimed at lowering elevated serum cholesterol levels in individuals (the 'high-risk strategy') and in populations at high risk (the 'population strategy') require no basic modification in the light of present knowledge on the relationships between cholesterol and noncardiovascular disease mortality. PMID- 1632855 TI - Atherogenic effects in a non-human primate of Fusarium moniliforme cultures added to a carbohydrate diet. AB - Adding less than 0.5% w/w of culture material of strain MRC 826 of the fungus Fusarium moniliforme to a carbohydrate diet low in fat resulted in an atherogenic plasma lipid profile in a non-human primate. Simultaneously increased plasma fibrinogen and activity of blood coagulation factor VII could enhance atherogenesis. This unique potential for promotion of atherosclerosis was probably secondary to chronic hepatotoxicity as indicated by liver fibrosis and elevated cholesterol, albumin and the enzymes AST, ALT, LD, GGT and ALP in serum. The cholesterol and enzymes responded in proportion to the calculated doses of fumonisin mycotoxins in the F. moniliforme MRC 826 cultures. Fumonisins are water soluble and heat stable. Thrombotic, hepatotoxic, carcinogenic and cerebral effects of MRC 826 culture material and fumonisins are well known in non primates. The estimated fumonisin concentrations tested fall within a range due to natural contamination of human foods. The results suggest that all maize grain products should be analysed for fumonisins. PMID- 1632856 TI - Comparative studies on acid cholesterol esterase in renal blood vessels and aorta of control and hypercholesterolemic rabbits. AB - Decreased acid cholesterol esterase has been linked to cholesteryl ester accumulation and may be fundamental in the development of atherosclerosis. The present study compared cholesterol esterase activity with the accumulation of cholesterol and its esters in aorta, renal artery and renal preglomerular microvessels. Tissue was obtained from white New Zealand rabbits fed either a control or 2%-cholesterol diet for 1 month. Cholesterol esterase was increased in microvessels from cholesterol-fed animals when compared to aorta and renal artery. Cholesterol feeding generally produced an increase in cholesterol and cholesteryl ester accumulation in all vascular tissues. The percent distribution of esterified/total cholesterol in renal microvessels was decreased consistent with the concomitant increase in cholesterol esterase. In contrast, aorta and renal artery exhibited an increase in cholesterol and cholesteryl ester accumulation and an increase in the percent of esterified cholesterol consistent with a decrease in acid cholesterol esterase after cholesterol feeding. The data suggest that renal microvessels, when compared to aorta and renal artery, may be relatively protected from developing atherosclerotic microvascular lesions through an organ-specific increase in acid cholesterol esterase activity. PMID- 1632857 TI - The effect of EDTA on the oxidation of low density lipoprotein. AB - Low density lipoprotein (LDL) is routinely isolated and stored in buffers containing ethylene-diaminetetra-acetic acid (EDTA) to inhibit its autoxidation. We have investigated the effect of EDTA on LDL oxidation by both copper ions and macrophages. LDL oxidation by macrophages in Ham's F-10 medium containing 6 microM iron showed a large and concentration-dependent increase when EDTA was added up to about 10 microM. EDTA concentrations above about 10 microM progressively inhibited LDL oxidation as measured by macrophage degradation, thiobarbituric acid-reactive substances and electrophoretic mobility. The oxidation of LDL by 1 microM copper in Ham's F-10 medium, measured by macrophage degradation, also showed a large increase with low concentrations of EDTA (1-3 microM), with higher concentrations (10 microM or above) strongly inhibiting the oxidation. In a simple phosphate buffer, however, EDTA simply inhibited the oxidation of LDL by copper with equimolar amounts of EDTA to copper giving a complete inhibition. The results of this study indicate that when LDL oxidation by cells or by copper in Ham's F-10 medium is investigated, more oxidation may be obtained if the EDTA is not previously removed from the LDL preparation. PMID- 1632858 TI - Genetic and environmental determinants of factor VII coagulant activity in ethnic groups at differing risk of coronary heart disease. AB - It has been shown previously that individuals possessing the Gln353 allele of factor VII have significantly lower factor VIIc levels. In this population based study of Europeans, Afro-Caribbeans and Gujarati Indians, the Gln353 allele was associated with lower factor VIIc in all groups, carriers having factor VIIc levels 20-25% below the group mean. Although the Afro-Caribbeans had the lowest factor VIIc levels, the frequency of the Gln353 allele was not different from the European sample. However, in the Gujaratis, the frequency of the Gln353 allele was significantly higher than in the Europeans (0.25 compared to 0.09, P less than 0.001). Factor VIIc is known to be positively correlated with plasma triglyceride levels, although the Gujaratis, having the highest mean triglyceride levels, did not have the highest mean factor VIIc levels. On examination of the relationship between triglycerides and factor VIIc in the Gujaratis there was a correlation (r = 0.23, P = 0.13) in individuals homozygous for the factor VII Arg353 allele, but no correlation (r = 0.001, P = 0.5) among Gln353 carriers. This striking difference suggests that the effect of triglycerides on factor VIIc is genotype specific and thus provides an example of gene-environment interaction. The high frequency of the Gln353 allele, with its associated lack of relationship between triglyceride and factor VIIc levels, may explain the lower than expected factor VIIc levels in the Gujaratis. PMID- 1632859 TI - The effect of probucol on HDL-mediated sterol translocation and efflux from cells. AB - It has been suggested that the antioxidant drug probucol can prevent arterial cholesterol accumulation in part by promoting HDL-mediated cholesterol removal from cells. In this study, the effect of probucol in vitro on the interaction of HDL3 with cultured skin fibroblasts, bovine aortic endothelial cells and human monocyte-derived macrophages was tested. Treatment of cholesterol-loaded cells with up to 20 microM probucol had no effect on [3H]cholesterol efflux from plasma membranes. No effect of probucol on HDL3-mediated efflux of labeled sterol was seen after intracellular sterol was labeled either with the biosynthetic precursor [3H]mevalonolactone or after incubation with lipoprotein-associated [3H]cholesterol linoleate. Further, no effect of probucol on cell cholesterol mass efflux was observed. Thus these results demonstrate that probucol does not affect movement of sterol from different cellular radiolabeled sterol pools. Within the limitations of cell culture studies, it is suggested that the proposed antiatherogenic effect of probucol in vivo is not likely to be the result of modulation of major cellular pathways for removal of cholesterol. PMID- 1632860 TI - Glucose tolerance, plasma insulin, HDL cholesterol and obesity: 12-year follow-up and development of coronary heart disease in Edinburgh men. AB - The insulin response to a standard oral glucose tolerance test (OGTT) and other anthropometric and biochemical risk factors for coronary heart disease (CHD) were measured in a random sample of 107 Edinburgh men, who were initially studied in 1976 when they were 40 and who were reexamined in 1988-89. Fasting glucose and glucose response to OGTT were higher in 1988-89 than in 1976. In contrast, insulin levels did not differ between the initial and follow-up study either before or after the glucose load. Body mass indices increased, except triceps skinfold. Changing patterns in both fasting and OGTT insulin or glucose levels in individuals were related to changes in bodyweight or in subscapular skinfolds. Modifications in serum total and HDL cholesterol were related to changes in fasting insulin and insulin area, respectively, but not to glucose data. Eleven men developed clinical CHD. Neither glucose nor insulin measures obtained in 1976 differed between those with and without CHD. Weight-height index and abdominal skin-folds were higher in those with CHD. HDL cholesterol was significantly lower (P less than 0.05). Abdominal skin-fold but not body mass index remained significant when adjusted for HDL cholesterol. This small study confirms the importance of central obesity and low HDL cholesterol but failed to identify insulin as a risk factor for CHD in this Scottish population. PMID- 1632861 TI - Inhibition of cholesterol synthesis in vitro by extracts and isolated compounds prepared from garlic and wild garlic. AB - Using a modified liver homogenate model to assay for the inhibition of cholesterol biosynthesis, different garlic and wild garlic extracts as well as pure compounds isolated from them were investigated for their influence on cholesterol synthesis. Chloroform and acetone/chloroform extracts of garlic and wild garlic inhibited cholesterol synthesis 44-52% at a concentration of 166 micrograms/ml, while the 5 individual sulfur-containing compounds ajoene, methylajoene, allicin, 2-vinyl-4H-1,3-dithiin and diallydisulfide inhibited cholesterol synthesis by 37-72% (10(-3) M corresponding to 234, 208, 162, 144, 146 micrograms/ml, respectively). Ajoene, 2-vinyl-4H-1,3-dithiin and allicin show IC50 values of 6.4, 7.2 and 9.4 x 10(-4) M, respectively. The results demonstrate that garlic and wild garlic may reduce serum cholesterol levels primarily by inhibiting cholesterol synthesis if taken in sufficient amount and that this effect arises from a mixture of multiple compounds from the sulfur-containing class of thiosulfinates, ajoenes and dithiines. Wild garlic extracts showed nearly identical efficiency to garlic extracts. PMID- 1632862 TI - Neopterin levels in patients with coronary artery disease. PMID- 1632863 TI - Endothelial cell damage and homocysteine. PMID- 1632864 TI - Human serum gangliosides in hypercholesterolemia, before and after extracorporeal elimination of LDL. AB - Total content, pattern and transport by lipoproteins of gangliosides have been studied in the sera of 10 patients with hypercholesterolemia and manifest cardiovascular disease. Half of the patients with hypercholesterolemia and 3 healthy controls were treated with heparin-induced extracorporeal LDL precipitation (HELP). In the sera of the untreated group total gangliosides and cholesterol were elevated about 2-fold. Ratios of normal ganglioside components were not altered and abnormal ganglioside species not detected. Treatment with HELP resulted in an almost selective removal of lipid-bound sialic acid carried on LDL. The re-increase of total serum gangliosides was strictly correlated to that of LDL-cholesterol and apolipoprotein B. Total gangliosides and ratios of individual components carried on single LDL- and HDL-particles were not altered by the HELP treatment. Our results indicate that gangliosides are excreted into the serum along with nascent apolipoprotein B-containing lipoproteins, which are of hepatic origin. In hypercholesterolemia excretion of gangliosides into the circulation is elevated and surplus of circulating gangliosides is bound to increased numbers of 'atherogenic' LDL. Biosynthesis of different ganglioside components, most probably by the liver, and total amount of gangliosides bound to lipoprotein particles seem not to be altered. PMID- 1632865 TI - Metabolic effects of dietary stearic acid in mice: changes in the fatty acid composition of triglycerides and phospholipids in various tissues. AB - The fatty acid patterns of triglycerides and phospholipids extracted from adipose tissue, liver, heart, kidney, spleen, and lung of 3 groups of C57BL/6 mice were determined after feeding diets rich in palmitic acid (16:0) (high palmitic: 16:0 = 45.1% of total fatty acids), stearic acid (18:0) (high stearic: 18:0 = 42.9% of total fatty acids) and oleic acid (18:1) (high oleic: 18:1 = 79.7% of total fatty acids) for 9 months. Triglyceride content of adipose, liver, heart, kidney, lung and spleen tissues was significantly enriched in palmitic acid in mice fed the high palmitic diet (range among all tissues: 19.9% +/- 0.2% to 29.0% +/- 1.9% of total fatty acids) and in oleic acid in mice fed the high oleic diet (range 56.0% +/- 1.9% to 71.6% +/- 1.2%). The stearic acid content of organ triglycerides in mice fed the high stearic diet ranged from 3.7% +/- 0.3% to 10.8% +/- 1.2%; however, the content of oleic acid on this diet (range: 57.0% +/- 1.8% to 71.4% +/- 1.7%) was similar to the one observed in mice fed the high oleic diet. In all organs, phospholipids had a significantly higher percentage of stearic acid (range: 23.5% +/- 0.9% to 51.5% +/- 6.6%) than triglycerides, regardless of diet. To evaluate the production of oleate from stearate and palmitate, 2 groups of mice were fed the high palmitic and the high stearic diets for 1 week and then injected intravenously with [1-14C]palmitate and [1-14C]stearate and the amount of labelled oleate in liver triglycerides was measured.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632866 TI - Lipid levels in monocytes of patients with moderate hyperlipoproteinemia. AB - Recent studies suggest that circulating blood monocytes may serve as a lipid clearance system in early atherosclerotic lesions. To evaluate the influence of moderate hyperlipoproteinemia on monocyte lipid concentrations, we measured fasting serum and monocyte lipid levels in 7 healthy individuals, in 7 patients with primary hypercholesterolemia and in 17 patients with secondary dyslipidemia due to chronic renal failure; 10 of these patients were treated by hemodialysis (HD) and 7 patients by continuous ambulatory peritoneal dialysis (CAPD). The hypercholesterolemic patients had elevated serum levels of total cholesterol, LDL cholesterol and apolipoprotein (apo) B, but normal plasma triglycerides. Patients on dialysis had elevated serum levels of triglycerides, serum cholesterol (CAPD only) and VLDL- and LDL-cholesterol (CAPD only) and apo B (CAPD only), whereas HDL-cholesterol and apo A-I levels (HD only) were decreased. In monocytes, we measured the content of free cholesterol (FC), cholesteryl esters (CE) and triglycerides (TG). The normal mean intracellular concentrations of FC, CE and TG were 48.3, 1.7 and 2.4 micrograms/mg cell protein, respectively. All monocyte lipid levels were similar in patients and controls, with the exception of a decreased content of FC (30.8 micrograms/mg) in monocytes of HD patients. We conclude that moderate increases in serum lipoprotein lipid levels are not associated with lipid accumulation in monocytes. PMID- 1632867 TI - Heparin stimulates proteoglycan synthesis by vascular smooth muscle cells while suppressing cellular proliferation. AB - We studied the effect of heparin on proteoglycan synthesis by bovine aortic smooth muscle cells in culture. Confluent, growth-arrested cells were incubated with [35S]sulfate, [3H]glucosamine or [3]serine in the presence of 0-600 micrograms/ml heparin. Metabolically labeled proteoglycans secreted into the culture medium and associated with the cell layer were analyzed. In cultures treated with heparin there was a dose-dependent increase in [35S]sulfate incorporation into secreted proteoglycans which reached a maximum (35% above controls) at 100 micrograms/ml heparin. At higher concentrations of heparin, the stimulatory activity declined and finally disappeared. Radioactivity in cell associated proteoglycans increased significantly (16% above controls) only in cultures treated with 100 micrograms/ml heparin. Heparin also produced similar increases in the incorporation of [3H]glucosamine and [3H]serine into secreted and cell-associated proteoglycans. While chondroitin sulfate, dermatan sulfate and heparan sulfate were elevated in the media, only chondroitin sulfate and heparan sulfate were increased in the cell layer. Heparin did not alter the degradation of proteoglycans. Heparin, while inhibiting the proliferation of subconfluent smooth muscle cells, also stimulated to a greater extent the incorporation of [35S]sulfate into proteoglycans. Other glycosaminoglycans, such as heparan sulfate, dermatan sulfate, heparin hexasaccharide and Sulodexide caused a significant but lesser stimulation of proteoglycan synthesis, while chondroitin sulfates and hyaluronic acid had no effect. Gel filtration chromatography of proteoglycans and their constituent glycosaminoglycans from heparin-treated and untreated cultures showed no differences in their molecular size. The results indicate that heparin can stimulate proteoglycan synthesis by vascular smooth muscle cells irrespective of their state of proliferation. This might have implications in vessel wall repair and arterial wall lipid deposition. PMID- 1632869 TI - Dietary vitamin E and the attenuation of early lesion development in modified Watanabe rabbits. AB - Modified Watanabe heritable hyperlipidemic rabbits (M-WHHL) were fed either standard rabbit diet or diet supplemented with 0.5% wt/wt of the lipophilic antioxidant vitamin E (d,l-alpha-tocopherol). Animals of 10-12 weeks of age were divided into two groups matched for distribution of serum cholesterol levels at the beginning of the 12 week study period. A significant hypocholesterolemic response to vitamin E feeding was observed throughout the study. Vitamin E supplementation increased serum vitamin E levels approximately fourfold and restricted ex-vivo copper mediated oxidative modification of low density lipoprotein (LDL) as quantitated by fluorescence at 430 nm. Post mortem examination of aortic tissue revealed a significant (32%) inhibition of surface area lesion involvement in the arch region as determined by image analysis. It is concluded that administration of vitamin E to M-WHHL rabbits brings about a significant hypocholesterolemic response, confers on LDL significant protection against oxidative modification and either or both contribute to the inhibition of early aortic lesion development. PMID- 1632868 TI - Hyperhomocyst(e)inemia, anti-estrogen antibodies and other risk factors for thrombosis in women on oral contraceptives. AB - Hyperhomocyst(e)inemia was shown to be associated with vascular occlusion in atherosclerotic patients. We have conducted a study to determine if hyperhomocyst(e)inemia was also related to the vascular events observed in women on oral contraceptives, presumably having little or no atherosclerosis. Two hundred women receiving oral contraceptives were included in the study: 100 were healthy controls and 100 had documented vascular occlusion. Determination of serum homocyst(e)ine and anti-estrogen antibody levels wore performed under blind conditions. They were evaluated in logistic regression models in which age and smoking were also included. Women with vascular occlusion had higher levels of homocyst(e)ine (P less than 0.001) and of anti-estrogen antibodies (P less than 0.001) when compared to controls. They were also older (P less than 0.001) and more frequently smokers (P less than 0.05). The above mentioned variables were, in isolation, independent predictors of vascular occlusion. Moreover, a model assessing those variables and their interactions indicated that the levels of anti-estrogen antibodies and smoking increased the predictability in older women, as well as the levels of age-adjusted homocyst(e)ine. The study suggests that the above factors can identify women at risk and that determination of anti-estrogen antibodies and homocyst(e)ine levels may help to detect women predisposed to vascular occlusions when taking oral contraceptives. PMID- 1632870 TI - Adipose tissue fatty acids in Scottish men and women: results from the Scottish Heart Health Study. AB - The fatty acid composition of adipose tissue from 4114 men and women across 22 districts of Scotland is described. A biopsy of subcutaneous adipose tissue was obtained from the upper arm using a skin biopsy punch. Overall the proportion of saturated fatty acids was lower in women and those of monounsaturated and polyunsaturated higher than in men. There were significant effects of age on adipose tissue fatty acid composition, particularly in women, where the proportion of saturated fatty acids decreased and that of monounsaturated fatty acids increased with advancing age. The fatty acid composition of adipose tissue varied among the districts studied. The district standardised mortality ratio for coronary heart disease was positively correlated with the district mean oleic acid value and inversely correlated with the district mean linoleic acid value. This paper supports the importance of adipose tissue fatty acids as indicators of risk factor status for coronary heart disease. PMID- 1632871 TI - Visceral fat accumulation measured by magnetic resonance imaging in relation to serum lipids in obese men and women. AB - In 91 apparently healthy obese subjects (45 premenopausal women and 46 men) the associations between specific fat depots and serum lipids were studied. Magnetic resonance imaging was used to quantify fat depots at abdominal and hip level. In women, an accumulation of visceral fat was associated with a less favourable lipid profile, even after adjustment for age and body fat percentage: higher triglycerides levels (P less than 0.001), lower levels of HDL-cholesterol (P less than 0.01) and a diminished HDL-cholesterol/LDL-cholesterol ratio (P less than 0.01). In men, however, the significant inverse relationship between an abundance of visceral fat and the HDL-cholesterol/LDL-cholesterol ratio and the significant positive correlations with total-, LDL-cholesterol and triglycerides disappeared after adjustment for age and fat percentage. Within each sex, subcutaneous fat neither at abdominal level nor at hip level was significantly related to serum lipids. It is concluded that there are gender differences in the associations between visceral fat accumulation and serum lipids. PMID- 1632872 TI - Antioxidant status in relation to free radical production during stable and unstable anginal syndromes. AB - Lipid peroxidation and the antioxidant status were studied in male patients having stable angina (SA) and unstable angina (UA) pectoris and the results were compared with that of controls. Lipid peroxides (LPx) and conjugated dienes (CD) were found to be elevated in patients with both SA (LPx: 3.96 +/- 1.07, P less than 0.001; CD: 357.09 +/- 66.23, P less than 0.01) and UA (LPx: 4.66 +/- 1.33, CD: 373.33 +/- 49.82, P less than 0.001) than in controls (LPx: 3.22 +/- 0.86, CD: 335.15 +/- 60.27). In SA, the erythrocytes expressed a diminished activity of superoxide dismutase (SOD) (SA: 435.59 +/- 76.02, control: 651.69 +/- 145.90, P less than 0.001) and normal activities of catalase and glutathione peroxidase, whereas in UA it showed enhanced activities of both SOD (UA: 735.72 +/- 145.67, P less than 0.01) and catalase (UA: 21.94 +/- 6.26, control: 18.69 +/- 6.37, P less than 0.01). A significant increase was also noticed in the levels of ceruloplasmin and vitamin E during both types of angina, but not alteration was observed in the levels of transferrin. Further, the patients with diabetes showed maximum levels of lipid peroxides compared to smokers and hypertensives. The level of lipid peroxides was also observed to increase with the severity of disease. This study indicates that free radicals are involved in the pathogenesis and progression of atherosclerotic heart disease. PMID- 1632873 TI - Evaluation of elastic structural change in coronary atherosclerosis using scanning acoustic microscopy. AB - Coronary atherosclerotic lesions were observed by scanning acoustic microscopy (SAM), a technique which can visualize regions of differing elasticity. Three regions, i.e., dark (dR), intermediate (iR) and bright (bR) demonstrating differences in acoustic reflection intensity and the velocity of surface acoustic waves, were seen in the lesions. Furthermore, lipid-positive areas were found to be dR and iR and fatty crystalline areas were observed only in iR regions by polarizing microscope. These phase transitions of fat affected the acoustic properties in each region. According to SAM images, intimal structural changes were classified into three types, minimum structural change (type I), the overcrowded net-like dR structure (type II) and markedly disturbed structure with a decrease of dR (type III). The medial structure change was also classified into three types paralleling the decrease of dR (types M1, M2 and M3). Intimal type II with a large degree of thickening and intimal type III with medial type M3 were highly prominent in the acute myocardial infarction (AMI) group (P less than 0.01). Therefore these results suggest that the anisotropic elasticity induced by micro-elastic changes in the arterial wall may be associated with functional disturbance of the vascular wall. PMID- 1632874 TI - Vascular contraction in perfused carotid arteries of cholesterol-fed rabbits. AB - The purpose of the present study was to investigate the effects of hypercholesterolemia on sympathetic vascular responsiveness in the perfused rabbit carotid artery. Two groups of rabbit carotid arteries were evaluated for the simultaneous measurement of noradrenaline (NA) release and vasoconstrictor response induced by electric nerve stimulation and for exogenous NA-induced vasoconstriction in vitro. One group of rabbits was fed a diet containing 0.5% cholesterol for 2 weeks and the other group was fed standard rabbit chow. By scanning electron microscopy, monocytes adhering to the endothelial cells and penetrating into the subendothelium were observed. Neither endothelial denudation nor platelet adhesion could be detected. Rabbit carotid arteries were cannulated and perfused with a physiological solution at a constant flow rate. The vessels were subjected to both transmural field stimulation (TFS; 1.5-24 Hz) and exogenous NA administration. TFS caused a frequency-dependent increase in endogenous NA release with subsequent pressor responses in both groups. Exogenous NA also induced a dose-dependent pressor response, but a significant reduction was observed in the cholesterol-fed group. Methoxamine induced a similar response in both groups. It was concluded that hypercholesterolemia decreased the sensitivity of extrajunctional alpha-receptors in the perfused rabbit carotid artery. PMID- 1632875 TI - Alcohol dose and low density lipoprotein heterogeneity in squirrel monkeys (Saimiri sciureus). AB - The present study was designed to determine whether normolipidemic male squirrel monkeys (Saimiri sciureus) exhibit low density lipoprotein (LDL) heterogeneity similar to that observed in humans and if present, whether LDL subfractions are altered by consumption of low vs. high dose ethanol (EtOH). Primates were divided into three groups designated control, low, and high EtOH and fed isocaloric liquid diets containing 0%, 12% and 24% of calories as EtOH, respectively, for 6 months. The 12% EtOH caloric level resulted in a modest, non-significant increase in high density lipoprotein (HDL) cholesterol and no change in LDL cholesterol or plasma apolipoprotein B (apo B), while the 24% dose produced significant elevations in plasma, LDL and HDL cholesterol and apo B. Using a single-spin density gradient ultracentrifugation procedure developed for humans, three distinct LDL subclasses designated LDL1a (d = 1.031 g/ml), LDL1b (d = 1.038 g/ml) and LDL 2 (d = 1.046 g/ml) were isolated from all three treatment groups. Monkey LDL subfractions were nearly identical to very light, light and heavy LDL subspecies isolated from human plasma in terms of their: (1) isopycnic densities following ultracentrifugation; (2) co-migration as single bands with beta electrophoretic mobility in cellulose acetate and agarose electrophoretic gels; (3) size-dependent migration pattern in polyacrylamide gradient electrophoretic gels; (4) co-migration as a single band corresponding to apo B-100, following SDS polyacrylamide gel electrophoresis; and (5) decrease in total cholesterol/protein ratios with increasing LDL subclass density. Although there were no treatment differences in LDL particle size, within each treatment group, mean particle size for each LDL subfraction was significantly different from every other subfraction. Low (12%) dose alcohol had no effect on LDL subfraction mass relative to controls while high alcohol consumption resulted in marked increases in all lipid (except triglyceride) and protein of the larger, buoyant LDL subspecies (LDL1a and LDL1b). Moreover, the best correlation between plasma apo B and LDL subfraction total mass was demonstrated with LDL1b (r = 0.735). Since neither the lipid nor the protein concentration of the small, dense, purportedly more atherogenic, LDL2 changed with the 24% EtOH dose, we propose that the LDL subfraction alterations associated with high alcohol intake in squirrel monkeys (increased LDL1a, increased LDL1b, LDL2 no effect) may represent a compensatory response to modulate the overall atherogenic lipoprotein profile associated with elevations in total LDL cholesterol and plasma apolipoprotein B. PMID- 1632876 TI - The possible role of hemorheology in atherothrombogenesis. AB - Conventional risk factors predict only about 30-50% of incidental cases in cardiovascular diseases, which are still the leading cause of death in western societies. During the last decade, the importance of thrombosis as an essential mechanism in acute myocardial infarction (AMI) and stroke has been established. The introduction of thrombolysis has led to an impressive reduction in AMI case fatality and possibly also to a substantial amelioration of its prognosis. Evidence from experimental, clinical and epidemiological studies suggest, that several hemostatic and hemorheological factors (e.g., fibrinogen, Factor VII, plasma viscosity, hematocrit, red blood cell aggregation, total white cell count) might not only play an important role in the evolution of acute thrombotic events, but may also take part in the pathophysiology of atherosclerosis. An increasing number of studies reports altered hemostatic and hemorheological parameters to be associated with smoking, hyperlipoproteinemia, and high blood pressure, as well as with adverse dietary habits and other life-style factors. To date, their way of interaction with the atherosclerotic process is poorly understood. Hemorheological or hemostatic mechanisms that might promote thromboatherogenesis include the predisposition to thrombosis via a hypercoagulable state, the enhancement of atherosclerosis by fibrinogen and its metabolites, and finally the reduction of blood flow through various rheological effects (e.g., increase in plasma viscosity and red cell aggregation, or leukocyte activation). Future research should focus in more detail on the interrelationship between accepted risk factors and the hemostatic system as well as hemorheological parameters. Deeper insight into the mechanisms involved might lead to new preventive strategies as well as to therapeutic procedures in the management of atherosclerosis and associated thrombotic events. PMID- 1632877 TI - Learning and consciousness during general anesthesia. PMID- 1632878 TI - Retroviruses that express different ras mutants cause different types of tumors in chickens. AB - We have used replication-competent retroviral vectors to express avian and murine ras genes in cultured chick embryo fibroblasts (CEF) and in chickens. Since the viral vectors are identical, it is possible to compare the oncogenic potential of the ras genes directly. The normal (12 gly) form of chicken c-Ha-ras is not oncogenic in vivo, nor does high-level expression transform CEF. Expression of murine v-ras or modified forms of chicken c-Ha-ras with either lysine or glutamine at position 12 transforms CEF and causes tumors in birds. However, the oncogenic potential of the transforming ras genes is different; the viruses that express the genes with lysine and glutamine at position 12 cause a distinct spectrum of tumors. PMID- 1632880 TI - The molecular basis of CD46 polymorphic expression and demonstration of a protective role against lysis by xenosera. PMID- 1632879 TI - Expression of the CD46 antigen, and absence of class I MHC antigen, on the human oocyte and preimplantation blastocyst. AB - Expression of CD46 and class I major histocompatibility complex (MHC) antigens by human oocytes and 6-8-day unhatched expanded preimplantation blastocysts has been studied by immunocytochemistry. The CD46 antigen, a cell surface complement regulatory protein, was expressed by unfertilized oocytes as well as strongly by both the inner cell mass and trophectoderm of preimplantation blastocysts. In contrast, class I MHC antigens were not usually expressed by either oocytes or blastocysts. These data support the concept that gametes and embryonic cells involved in fertilization and early implantation events, respectively, may be protected from immunological recognition or attack both by the lack of class I MHC antigens and by expression of the CD46 complement regulatory protein. PMID- 1632881 TI - [Severe respiratory insufficiency as the first manifestation of AIDS]. PMID- 1632882 TI - Chemical prospecting: hope for vanishing ecosystems? PMID- 1632884 TI - [Ethical and deontological problems in the use of electronic data processing in nursing]. AB - This article deals with the ethical and moral dilemmas the nursing profession faces today in regards to issues related to the computer technology. Such ethical dilemmas in nursing have been documented in four major areas: (a) Safeguarding confidentiality, (b) determining the right to know and the right to decide, (c) allocating limited resources, and (d) maintaining professional standards. PMID- 1632883 TI - Transfer of DDT used in malaria control to infants via breast milk. AB - The transfer of p,p'-DDT (1,1,1-tricholoro-2,2-bis(4-chlorophenyl)ethane) and its metabolites to infants via breast-feeding was studied in an area of KwaZulu, South Africa, where DDT is used to interrupt malaria transmission. Samples of whole blood were collected from 23 infants, together with samples of breast milk from their respective mothers. The mean sigma DDT (total DDT) in the whole blood was 127.03 micrograms.l-1 and that in the breast milk, 15.06 mg.kg-1 (milk fat). The % DDT (% DDT of sigma DDT) was significantly higher in the infant blood than in the breast milk (P less than 0.05). A multiplicative regression analysis indicated that sigma DDT increased significantly (P less than 0.01) in infant whole blood with infant age. Multiple regression showed that 70.0% of the variation in sigma DDT was due to the variation in parity of the mother, age of the infant, and the sigma DDT in breast milk. These variables accounted also for 76.3% of the variation in p,p'-DDE but only for 38.2% of that in p,p'-DDT. Organochlorines were therefore largely transferred to the infant from the mother, with DDT in the environment playing a secondary role. PMID- 1632886 TI - [Computer technology in nursing]. PMID- 1632885 TI - [Autologous blood transfusion]. AB - Homologous blood is not always available in adequate amounts and it has a number of undesirable effects for the patient. Autotransfusion prevents these problems. In this review, the criteria for patient selection, the technical procedures, the advantages and the potential risks are described. PMID- 1632887 TI - [Computers in nursing practice]. PMID- 1632888 TI - [Development of health information systems as part of an integrated hospital information system]. PMID- 1632890 TI - The search for genes for psychiatric illness. PMID- 1632889 TI - [Psychosocial problems in the aged--nursing interventions]. AB - This article deals with age-related problems, due to social structure and several other factors. Loneliness, confusion, and dementia of the aged, when they co exist with acute disease, are often reversible. When they happen independently create serious psychosocial problems, and gradually become irreversible. Appropriate nursing interventions for the prevention, control and correction of these geriatric problems are described. PMID- 1632891 TI - A systematic search for a bipolar predisposing locus on chromosome 5. AB - Chromosome 5 markers spanning the pter to the qter were used to examine linkage to bipolar illness in 14 pedigrees. Twenty-four loci were examined in 237 individuals, of whom 69 were either bipolars or schizoaffectives. Marker genotypes were determined for each individual and lod scores were calculated under a dominant disease model with a maximum penetrance of 85%, a disease gene frequency of 0.015, a variable age of onset, and a phenocopy rate of 0.001. Under the assumption that bipolar illness is genetically homogeneous, the total lod scores from all pedigrees with each marker were uniformly lower than -2.0, suggesting the absence of linkage to disease at any of these loci. Multipoint analysis allowed exclusion of intervals between markers. When lod scores were calculated allowing for heterogeneity, no subset of linked families was found. These results indicate that in our pedigree series almost the entire mapped region of chromosome 5 can be excluded for linkage to bipolar illness. PMID- 1632892 TI - Quantitative instrumental measurement of tardive dyskinesia: a review. AB - In this paper we review currently available quantitative instrumental techniques for the assessment of tardive dyskinesia (TD). We discuss the advantages and disadvantages of the use of accelerometers, electromyography, force gauges, position transducers, and Doppler ultrasound from both a diagnostic and a utilitarian perspective. Data obtained using these techniques appear to correlate significantly with patient scores on clinical rating scales. In some cases, the use of these techniques has facilitated the detection of subclinical dyskinesia and helped to differentiate TD from other movement disorders. We believe that a review of these qualitative techniques will be of interest to the clinician, as well as to investigators involved in studying TD. PMID- 1632893 TI - Applications of magnetic resonance spectroscopy to the investigation of neuropsychiatric disorders. AB - Magnetic resonance spectroscopy (MRS) can noninvasively characterize tissue composition and metabolism in vivo without the need for radioactive isotope administration. For the neuropsychiatrist interested in the functional basis of disease, MRS offers an investigative tool capable of studying a wide variety of neuropsychiatric disorders. This report provides an overview of how MRS works, current and potential clinical applications for specific psychiatric populations, and limitations of the technology. PMID- 1632894 TI - Phosphorylation of prolactin and growth hormone. AB - To determine whether GH and prolactin could be phosphorylated, turkey GH, chicken GH, chicken prolactin and turkey prolactin were incubated in vitro with the catalytic subunit of protein kinase A and [gamma-32P]ATP. Phosphorylation was assessed after sodium dodecyl sulphate-polyacrylamide gel electrophoresis, Western blotting and autoradiography. Polyacrylamide electrophoresis showed that both purified native chicken GH and turkey GH were phosphorylated under the conditions employed. However, the glycosylated variant of chicken GH did not appear to be labelled. Chicken prolactin, turkey prolactin and the glycosylated variant of turkey prolactin were all intensely phosphorylated by protein kinase A. Ovine and rat prolactins could also be phosphorylated by protein kinase A. The phosphate content of different native prolactin (turkey, ovine and rat) and GH (ovine and chicken) preparations was also determined and found to be significant. Chicken pituitary cells in primary culture incorporated 32P in GH- and prolactin like bands isolated by non-denaturing polyacrylamide gel electrophoresis, and this was stimulated by phorbol myristate acetate. Phosphorylation of GH and prolactin may thus explain some of the charge heterogeneity of these hormones. PMID- 1632895 TI - RNA-protein interactions in the 5' untranslated region of preproinsulin mRNA. AB - A comparison between species of the 5' untranslated region of preproinsulin mRNA revealed conserved sequences associated with a potential stem-loop structure. The present study was undertaken to determine whether specific protein interactions exist with mRNA sequences involved in the formation or stabilization of this structure in the 5' untranslated region. 32P-Labelled RNA probes corresponding to sequences from this region were synthesized by an in-vitro transcription reaction and used in electrophoretic mobility shift and u.v.-crosslinking studies with cytoplasmic protein extracts from a number of cell lines. Specific protein-RNA interactions were mapped to a sequence located between nucleotides -21 and -50 upstream of the AUG start codon. A number of proteins of molecular mass 25 kDa, 40kDa, 46kDa, 58kDa, 69kDa, 97kDa, 110kDa and 160kDa were specifically crosslinked to this sequence. The observed specific protein-RNA interactions in the 5' untranslated region may affect the activity of preproinsulin mRNA. PMID- 1632896 TI - Hormonal induction of malic enzyme in rat hepatocytes cultured on laminin-rich gels. AB - The levels of malic-enzyme mRNA and activity were determined in primary cultures of adult rat hepatocytes maintained on either rat-tail collagen or a laminin-rich substratum. Cells plated on laminin-rich gels exhibited substantially improved patterns of albumin and malic-enzyme expression when compared with cells maintained on rat-tail collagen. Moreover, hepatocytes plated on the laminin-rich matrix displayed marked malic-enzyme inducibility in response to tri iodothyronine and dichloroacetate, especially in the presence of insulin. However, Northern blot analysis revealed that the ratio of the amounts of the two major malic-enzyme mRNA species (2.0 and 3.1 kb) was reversed when compared with that found in the liver in vivo, the altered levels of these two species being closer to those found in non-hepatic tissues. These findings indicate that, although the hormonal responsiveness of isolated hepatocytes maintained on laminin-rich gels is markedly improved, and approaches the degree of induction demonstrated in the liver in vivo, the mechanisms of control differ, indicating a loss of liver-specific expression. PMID- 1632897 TI - Ovine follistatin: characterization of cDNA and expression in sheep ovary during the luteal phase of the oestrous cycle. AB - We have isolated ovine follistatin cDNA from an ovarian follicle cDNA library and determined its sequence. The deduced amino acid sequence of the ovine follistatin precursor is highly homologous (greater than 97%) to the porcine, human and rat follistatins. Northern analysis was used to characterize follistatin gene expression in ovaries of adult ewes, collected from days 11 to 13 of the oestrous cycle. Two major (about 2.7 kb and 1.5 kb) and one minor (about 0.5 kb) transcripts were detected in polyadenylated RNA extracted from ovarian follicles and corpora lutea. The degree of expression of the transcripts varied in the two ovarian compartments, with the 2.7 kb species predominating in the follicles and the 1.5 kb species being more abundant in the corpora lutea. No transcripts were detected in stromal tissue containing preantral follicles of less than 1 mm. PMID- 1632899 TI - [St. Laurentius Hospital Roermond. Unearthly noises]. PMID- 1632898 TI - [Continuing education oncologic nursing]. PMID- 1632900 TI - [316 days--Werner update 8]. PMID- 1632901 TI - [Research in Higher Nursing Education. Study day of the Society of Faculty in Higher Education Nursing]. PMID- 1632902 TI - [Nursing models in nursing of the mentally retarded]. PMID- 1632903 TI - [Roy in the Z (mental retardation nursing)]. PMID- 1632904 TI - [Composition of the patient group. According to a type classification of therapeutic milieus in psychiatric care]. PMID- 1632905 TI - [Nutrition in psychiatry. Carbohydrates and depression]. PMID- 1632906 TI - [The significance and use of somatometric reference values of weight and height in pediatric and epidemiologic practice]. AB - If we know growth as cellular phenomenon to addition of matter to protoplasm, is valid how a generic phenomenon, within normality range, is a species attribute, and in the human would be of psychosocial order. It is a appointed with only somatometrie is not valid criterion in the diagnosis of desnutrition, but is a excellent point in order to identification of risk population. In this order is necessary reference values useful, well elaborated, with adequate samples. It is commented about weight and height as a adequate parameters for measuring growth. It is convenient the adoption of an unique international somatometric reference tables if we considered growth how a generic and species phenomenons. Were analyzed 2 works of reference tables used in our country. Finally is commented the convenience of use of an unique international reference tables. It is proposed the somatometric reference tables published for the WHO, in 1983, and were discussed the razons for this recommendation. PMID- 1632907 TI - [The molecular genetics of cystic fibrosis: the delta F508 allele in Mexican families]. AB - We have initiated the screening of the delta F508 cystic fibrosis (CF) mutation in our country basing our study on the polymerase chain reaction technique. In a sample of 10 western and a northeastern Mexican families that have at least one CF affected child, we found a delta F508 frequency of 59.1% among CF chromosomes. This frequency is similar to those reported for Spain. Furthermore, we found a correlation between the delta F508 allele and pancreatic insufficiency. This paper points out the advantage of the polymerase chain reaction technology for the analysis of Mendelian disorders. PMID- 1632908 TI - [The prevalence of elevated arterial pressure and risk factors in adolescents in the Federal District of Mexico]. AB - To develop studies on blood pressure (BP) of young population, such as adolescents, is important, because it is an early way to obtain information about the factors that could influence or modify the levels of BP. A group of 1,146 junior high school students from Mexico City was studied, by means of a questionnaire to identify risk factors, which were classified as: 1. inherent factors, 2. acquired risks and 3. family background. A significant association was observed related to inherent factors in scholars, mainly at monarch age with an odds ratio of 2.45; and confidence intervals of (1.05-5.63) for systolic blood pressure (SBP) and 8.81 (4.44-17.54) for diastolic blood pressure (DBP). In relation to acquired risks, there was a positive association with the use of contraceptives. As for family background there was as important association, in the following order: obesity, diabetes and hypertension. Therefore, it may be said that since early ages there are risk factors for BP; although some of them were not significantly, they can not be excluded as risk factors because there is a possibility that a longer latency period may be needed for them to act as such. PMID- 1632909 TI - [The determination of pulmonary phospholipids in the gastric contents for an assessment of the respiratory distress syndrome]. AB - Since hyaline membrane disease (HMD) is an important cause of mortality and morbidity in preterm newborns, we decided to evaluate the utility of pulmonary phospholipid (PP) determination in gastric aspirate for confirmatory diagnosis. For that purpose we studied 31 preterm and 30 term babies and compared the results between them and PP in gastric aspirate and amniotic fluid from their mothers. All the term newborns were normal, with mean weight of 3,221, and 39 weeks of gestational age; the results of phosphatidyl inositol (PI) and phosphatidyl glycerol (PG) were positive. The premature babies had a mean weight of 2,424 g and 35 weeks of gestational age. Thirteen had respiratory distress, 4 transient tachypnea and 9 HMD. In this group the babies with PI present and PG absent developed respiratory distress without HMD. The test had sensibility of 69% and specificity of 100%, and in patients without PG and PI the sensibility and specificity was 100%. We concluded that this test has enough sensibility and specificity for the confirmation of HMD in gastric aspirate when the PI and PG are not present. PMID- 1632910 TI - [An evaluation of the 4 years of the Oral Rehydration Service of the Hospital Infantil de Monterrey]. AB - At four years of being founded the Service of Oral Hydration from Hospital Infantil de Monterrey, we carried out this investigation to know its productivity, to determine costs of internments, death rates due to diarrhea and dehydration in the hospital and at a State level. The statistics from the hospital were revised in the previous and subsequent years to the institution of the Service in September of 1986, so as the statistics of death due to diarrhea from the State Health Department. The cases attended were 12,139, from which 9,024 belonged to plan A, 2,983 to plan B and 72 to plan C. Three hundred (300) doctors were trained and nine (9) research studies were accomplished. A decrease was achieved from the hospital rate admission by diarrhea and dehydration, throw the oral dehydration therapy in a 66%, the mortality rate was reduced 72% and an expenditure of $619,243,480.00 pesos in drugs and auxiliary examinations of diagnostic was avoided. At a State level the general death rate due to diarrhea got a cutdown of 13.1 to 5.8, and in infants under a year old decreased from 275 to 122.3. The oral hydration therapy applied in the State seems to be the main reason in that results. PMID- 1632911 TI - [Fascioliasis in children. A study of 10 cases]. AB - These are the observation found in ten children with fascioliasis diagnosis at the Servicio de Parasitologia, of the Instituto Nacional de Pediatria, from 1979 to 1990; six children in scholar age; one prescholar and three teenagers; only one was female. Four of them lined at the State of Mexico; three at Morelos; one at Puebla, another one at Oaxaca and the other one at Mexico City. In nine of the watercress eaten was confirmed. The most important clinic manifestations were: fever, weight lose, paleness, hepatomegaly, hiporexia, right hypochondrium pain and diarrhoea. Diagnosis was established by: counterimmunoelectrophoresis, indirect haemagglutination and there were found eggs by simple sedimentation, Ritchie's method and microscopic study of duodenal sample. Leukocytes counts were between 11,000 and 34,000/mm3. Eosinophils were to 77% with 24,430 totals. Only in three of them haemoglobin was found under 9 g/dL. All of them had hypergammaglobulinemia. In nine patients the alkaline phosphatase was found in higher levels; only in three of them, transaminase, oxalacetic and glutamic piruvic were found in higher levels. The most effective drug in the treatment was dehidroemetine. PMID- 1632912 TI - [Cerebral infarct secondary to an intraoral injury from a spoon. A case report]. AB - We report the case of a 4-year-old female who developed an extensive cerebral infarction after trauma to the right peritonsillar area with a spoon. Blunt injury to the intima of the interna carotid artery promotes thrombus formation or clot embolization which results in an ischemic cerebrovascular event. We emphasize the need to prevent this rare complication of intraoral trauma in childhood. PMID- 1632913 TI - [Acute kidney failure due to stings by Africanized bees]. AB - Africanized bees are unique in their aggressive behavior, characterized by massive attacks during which the victims are injected an important amount of venom. For this reason, Africanized bees are extremely dangerous. Their venom contains biological toxic substances, mainly mellitin, phospholipases, histamine, hyaluronidase and apamin. Non-sensitized persons that survive a massive attack may develop acute renal failure, as a consequence of the severe hemolysis, rhabdomyolysis and shock. These complications may lead to acute renal tubular necrosis. Also, the clinical pattern and treatment of the acute renal failure secondary to bee stings are discussed. PMID- 1632914 TI - [Functional bladder capacity in enuretic patients]. PMID- 1632915 TI - [The diagnosis of human immunodeficiency virus infection in children under 18 months]. PMID- 1632916 TI - Untoward clinical effects after stereotactic radiosurgery for intracranial arteriovenous malformations. AB - Stereotactic radiosurgery has become one of the most acceptable means of treating deep-seated intracranial arteriovenous malformations, as well as being a useful adjunct in a number of other pathologies. One hundred and sixty patients are discussed, having follow-up of at least 2 years. Radionecrosis occurred in six patients and haemorrhage in the latent period prior to thrombo-obliteration in a further six. Successful thrombo-obliteration was ultimately achieved in 76% of patients. As a bonus, epilepsy was improved in 29 of 48 patients presenting with seizures and worsened transiently in only three of these. PMID- 1632917 TI - Paediatric craniopharyngiomas: a regional review. AB - Forty paediatric craniopharyngioma cases treated between 1956 and 1987 by conservative surgery (15), radical surgery (10), conservative surgery and radiotherapy (9) and shunting (6) are reviewed. The conservative surgery and radiotherapy group's local control and survival (100%) is significantly better than that of any other group. This group also achieved the most consistent level of employment or tertiary education. Overall morbidity was high. Overall survival has improved since 1976. Whether given as an adjuvant or salvage a radiotherapy dose of TDF 83 or greater gave a significantly better survival (100%) than lower doses. PMID- 1632918 TI - The fate of tumour rests following removal of acoustic neuromas: an MRI Gd-DTPA study. AB - The fate of capsular fragments left attached to vital structures at the time of otherwise total tumour removal was studied in 14 of 21 such patients who underwent acoustic neuroma surgery. Imaging using magnetic resonance Gd-DTPA at post-operative intervals of 6 months-12 years (mean 70 months) showed evidence of persistent tumour in half the patients. None of the patients had developed new symptoms and computed tomography had failed to demonstrate tumour recurrence. Persistence of the tumour was more likely if the residual fragments were not cauterized at the time of operation. Four of the seven persisting tumour rests showed evidence of gradual enlargement. The implications for patient management, particularly if an attempt is made to preserve hearing, are discussed. PMID- 1632919 TI - Unusual presentations of cerebral hydatid disease in children. AB - Three children with hydatid disease of the central nervous system (CNS) were seen. In two patients the lateral ventricles were involved, whilst one case involved the cerebellar hemisphere. In addition, one child presented with a deposit in the maxillary antrum, and deposits were also found in the liver. Operative removal of the deposits was performed, followed by post-operative treatment with praziquantel and albendazole. Investigation of other sites outside the CNS was undertaken for occult lesions. All hydatid cysts were clearly demonstrated on CT, but two cases posed the pre-operative problem of differential diagnosis from arachnoid cysts. PMID- 1632920 TI - Effect of pre- and postganglionic lesioning of the trigeminal nerve on cerebral blood flow and glucose metabolism following a subarachnoid haemorrhage in the squirrel monkey. AB - Simultaneous cerebral blood flow (CBF) and glucose metabolism (CMRglu) studies with a double isotope autoradiographic technique were applied to squirrel monkeys submitted to a unilateral pre- or postganglionic trigeminal lesion. The CBF values were not affected following a pre- or postganglionic lesion per se. In contrast, there was a global increase in the cerebral glucose uptake of about 50% as compared to controls following both kinds of lesions. Following a subarachnoid haemorrhage (SAH) 2-4 weeks after pre- or postganglionic trigeminal lesioning, there was a decrease in CBF similar to that seen in the control group. In the animals with a preganglionic lesion, the 50% increase in glucose uptake was not further augmented by a SAH and the increase in CMRglu was comparable to that found in control SAH animals. In the postganglionically lesioned monkeys, a SAH induced an additional increase in glucose uptake of about 50%. The findings suggest that the trigeminal system is involved in the regulation of cerebral metabolism via a brainstem centre. PMID- 1632921 TI - The outcome from acute subdural and epidural intracranial haematomas in very elderly patients. AB - Out of a consecutive series of 1082 operations performed on head-injured patients over a 9-year period, 28 cases of acute subdural haematomas (SDHs) or epidural haematomas (EDHs) occurring in patients aged between 80 and 100 years were selected. Mortality rates in these patients (100% in 2 EDHs, 88% in 26 SDHs) were significantly higher (p less than 0.01) compared with patients under 80 years (12% in 308 EDHs, 57% in 215 SDHs). Pre-existing diseases, primary events precipitating falls, and multiple system failure complicating the postoperative course accounted for most of the deaths. None of the patients operated upon with a Glasgow Coma Scale score of 11 or less survived. A typical 'talk and die' course occurred in two cases. Three patients, all operated on for SDH, survived and returned to their pre-injury conditions. It was concluded that, whilst the question as to whether to submit very old comatose patients to life-prolonging measures remains unsettled, there is a case for the prompt evacuation of extra axial clots in patients with minimal impairment of consciousness. PMID- 1632922 TI - Incidental pituitary macroadenomas. AB - Five cases of incidentally detected pituitary macroadenomas are described. All five had suprasellar extensions, but none had visual field defects as tested by computed perimetry. One patient had sellar changes seen on an X-ray film taken following a head injury, while the others were detected by computed tomography performed for seizures, stroke and meningitis. Four patients underwent trans sphenoidal surgery for suprasellar extensions with or without hypopituitarism, while one was managed conservatively as he had normal visual fields and pituitary function and there was a spontaneous decrease in size of the adenoma. The management of such incidental pituitary macroadenomas is discussed. PMID- 1632923 TI - New instrumentation for the assembly of shunt systems by a non-touch technique. AB - In modern neurosurgery there are many types of ventricular shunts, ventricular drains and access devices. These are composed of a variety of components which are best assembled and manipulated using a non-touch technique. A comprehensive and inexpensive set of instruments is described which is easy to sterilize and which will facilitate the easy manipulation and assembly of a wide range of these devices by a true non-touch technique. PMID- 1632924 TI - Carpenter's syndrome (acrocephalopolysyndactyly type II) with normal intelligence. AB - A 6-year-old girl with Carpenter's syndrome is reported who, in spite of a considerably distorted and small calvarium at birth, has normal mental development. Cranio-facial surgery was carried out in infancy, but its role in respect to mental development is difficult to assess since unoperated patients with normal intelligence and Carpenter's syndrome have been widely reported. Nevertheless, early cranio-facial surgery is recommended for cosmetic reasons. PMID- 1632925 TI - Solitary brainstem abscess successfully treated by microsurgical aspiration. AB - A case of pyogenic pontine abscess detected by computerized tomography scan in a 10-year-old boy is presented. While on broad-spectrum antimicrobial treatment, he deteriorated and developed new symptoms of respiratory distress. Microsurgical exposure of the abscess and aspiration of pus resulted in rapid improvement in his neurological state and radiological resolution of the lesion. The aim of this article is to emphasize the importance of prompt diagnosis and the role of surgical drainage of pus in the management of brainstem abscesses. PMID- 1632926 TI - Malignant paraganglioma of the glomus jugulare: a case report. AB - Jugular paragangliomas are noted for their tendency to recur, but frank malignant behaviour is rare. We report a case in which a patient harbouring a recurrent tumour of the glomus jugulare re-presented with metastatic spread to mediastinal lymph nodes. Review of the 16 reported cases provides information which can be a basis for management of the malignant form of this tumour. PMID- 1632927 TI - Ventriculo-ureteral shunt without nephrectomy. AB - Some patients with hydrocephalus cannot be adequately treated with either ventriculo-peritoneal or ventriculo-atrial shunts. Ventriculo-ureteral (VU) shunts are seldom considered in this group of patients because of the belief that nephrectomy is an essential part of the procedure. We report a case in which a VU shunt was performed with direct ureteral re-implantation and we suggest that a VU shunt is a reasonable alternative for the treatment of a patient with difficult to-manage hydrocephalus. PMID- 1632928 TI - Successful treatment of a pineal region epidermoid cyst by stereotactic aspiration. PMID- 1632929 TI - Fibromuscular hyperplasia of the internal carotid artery. A further cause of the 'moyamoya' collateral circulation. AB - Fibromuscular hyperplasia is a rare cause of internal carotid artery occlusion. We present a case where long stenoses of both internal carotid arteries were associated with terminal carotid occlusions and a ruptured basilar aneurysm. PMID- 1632930 TI - Paraganglioma of the cauda equina. PMID- 1632931 TI - Heterogeneity of hypertension. AB - Although all forms of hypertension have in common the finding of elevated blood pressure, further examination reveals great heterogeneity. The risk of hypertension is related not only to the level of blood pressure but also to the presence of other risk factors; the prevalence of hypertension is affected by demographic, clinical, and psychologic characteristics; the pathophysiology of hypertension reflects varying participation of salt-sensitivity, the renin angiotensin system, and other control mechanisms; and treatment responses differ among patients both with regard to the degree of blood pressure lowering by various therapies and the clinical benefit obtained. Knowledge of these heterogeneities at present is useful but only partial. Additional research is needed to improve prediction of hypertension, to enhance stratification of patients by the mechanisms and risk of their hypertension, to refine the matching of specific therapies and treatment goals to the underlying pathophysiology, and to facilitate transfer of evolving information to the clinician. PMID- 1632932 TI - Cell type and cell state specific antibodies in the analysis of early lesions of human atherosclerosis. AB - Studying the cell composition of lesions of human atherosclerosis can yield important information regarding the cellular interactions involved in the pathogenesis of this disease. We have used a panel of monoclonal antibodies, many developed in this laboratory, to study the cell composition of human fatty streaks. Results indicate that the predominant cell type in these lesions is the smooth muscle cell rather than the macrophage. Furthermore, using single and double labeling techniques, it was demonstrated that: (a) no expression of class II HLA antigens by smooth muscle cells could be documented; (b) the beta-chain of the platelet derived growth factor could be demonstrated within some macrophages in a small subset of lesions; and (c) only a very small fraction of the cell population express markers associated with cell proliferation, and those that do are largely macrophages and lymphocytes. PMID- 1632933 TI - Proliferative response of smooth muscle cells in hypertension. AB - A significant increase (up to 20% from about 10% in normals) in the number of smooth muscle cells (SMC) with tetraploid DNA content was found in the media and intima of human hypertensive aorta. A similar process was detected during normal human vessel aging. It was found that SMC from normal human aorta and normotensive rat aorta, which were able to incorporate 3H-thymidine, had diminished proliferative potency and a tendency to polyploidization in primary culture. We failed to detect a similar phenomenon in SMC obtained from aorta from spontaneously hypertensive rats. It was found that 10 mumol/L of norepinephrine significantly increased (by approximately twofold) the frequency of true polyploid cells in a subculture of rat aortic SMC. The effect of norepinephrine was blocked only by simultaneous action of alpha- and beta-adrenoreceptor antagonists. SMC polyploidization was also stimulated by simultaneous application of two direct activators of the second messenger systems, forskolin and phorbol 12-myristate-13-acetate. Thus, a subpopulation of SMC prone to polyploidization exists in normal vessels, and norepinephrine may be one of the mediators of the "hypertensive" response of vessel wall SMC, which probably occurs due to the synergism of two second messenger systems. PMID- 1632934 TI - Contractile rabbit aortic smooth muscle cells in culture. Preparation and characterization. AB - Investigations were conducted to determine whether rabbit aortic smooth muscle cells (SMC) reproduce their essential in situ features in culture. Enzymatically isolated cells in culture were compared with their in situ state in terms of myosin and caldesmon isoform expression, sensitivity to Ca(2+)-mobilizing agonists, and contractility. Protein marker expression was assessed by electrophoresis and quantitative immunoblotting, and intracellular free Ca2+ ([Ca2+]i) measurements were accomplished using indo-1, a Ca(2+)-sensitive fluorescent dye. Contraction of SMC grown on deformable silicone films was monitored optically. Before the onset of cell division (3 to 6 days in culture), SMC still contained significant although decreasing amounts of smooth muscle myosin (SM1 and SM2 isoforms) and they started to express nonmuscle-type myosin. The relative content of 150-kDa caldesmon decreased, whereas the expression of 77 kDa caldesmon increased during this period. In the confluent primary culture (11 days), SM1 was expressed, but 150-kDa caldesmon was hardly detectable. Histamine (10(-5) mol/L), serotonin (10(-6) mol/L), and thrombin (1.5 units/mL) contracted deendothelialized rings of rabbit aorta, but only histamine was able to elevate [Ca2+]i 2.5- to 3-fold and induce reversible contraction of primary nondividing cells. [Ca2+]i elevation in response to histamine was due both to Ca2+ mobilization from intracellular stores and Ca2+ flux across the plasma membrane. After the onset of proliferation, SMC regained the ability to elevate [Ca2+]i in response to serotonin and thrombin but lost the ability to contract. Thus, primary cultured quiescent rabbit aortic SMC (3 to 6 days in culture) retain the essential features of vascular SMC in situ (eg, smooth muscle specific contractile and regulatory proteins, vasoactive hormone sensitivity, and contractility). PMID- 1632935 TI - Humoral factor, intraplatelet calcium, and hypertension. AB - Plasma humoral factors which modulate the transmembrane distribution of sodium and calcium have been identified in hypertensive patients and have been hypothesized to be involved in the etiology of essential hypertension. In cross incubation experiments, we have found that plasma of hypertensive subjects elevated basal and stimulated intraplatelet calcium levels, while plasma of normal subjects has an opposite effect on platelets from hypertensives. Basal intraplatelet calcium in normal platelets was 108 +/- 5 nmol/L and rose to 142 +/ 3 nmol/L (P less than .001) after incubation in plasma from hypertensive patients. Platelets from hypertensive patients had basal calcium levels of 182 +/ 11 nmol/L which fell to 127 +/- 11 nmol/L (P less than .01) after incubation in normal plasma. Hypertensive plasma potentiated the rise in intraplatelet calcium in response to ADP and PAF. Hypertensive patients treated experimentally with plasmapheresis exhibited a disappearance of the plasma factor responsible for elevating intraplatelet calcium. These results indicate the presence of a plasma humoral factor in hypertensives which elevates intraplatelet calcium and sensitizes platelets to agonist stimuli. PMID- 1632936 TI - Altered sympathetic tone in hypertensives with angina and lowered threshold for pacing ischemia. AB - To determine the role of the sympathetic nervous system in myocardial ischemia with essential hypertension, plasma norepinephrine, heart rate (HR), blood pressure (BP), and the HR.BP double product at the time of silent ischemia during pacing and exercise treadmill test (ETT) were compared with basal values in 20 patients with sustained essential hypertension and stable angina, 3 to 60 days (12.6 +/- 11.6) after discontinuation of all antihypertensive and coronary vasodilator therapy. Group I (N = 6) had silent ischemia with a higher HR.BP product at ETT than at pacing (ratio = 157 +/- 10.4% [+/- SD] v a value in group II [N = 5] of 102 +/- 18.8 [P less than .01]. Group III (N = 9) had no silent ischemia at ETT or pacing. Group I v group II plasma norepinephrine levels at rest and with pacing silent ischemia were 76 +/- 37 v 138 +/- 36 pg/mL, P less than .02, and 101 +/- 50 v 230 +/- 43 pg/mL, P less than .01, respectively. In groups I and II plasma norepinephrine levels were significantly lower than those of group III. Eleven of 20 patients had ischemia on pacing or ETT. Left ventricular myocardial mass were greater (224 +/- 49 v 180 +/- 28 g, p less than .05), HR (67 +/- 13 v 76 +/- 11 beats/min, P = NS) and plasma norepinephrine levels at rest (104 +/- 47 v 241 +/- 99 pg/mL, P less than .01), pacing (160 +/- 81 v 338 +/- 94 pg/mL, P less than .01), and ETT (758 +/- 268 v 1203 +/- 611 pg/mL, P less than .05), were lower in patients with ischemia (N = 11, group II) than in patients without ischemia (N = 9, group III) on pacing or ETT. Eight patients were on reserpine prestudy; reserpine prestudy was associated with lower basal HR (63 +/- 9 v 76 +/- 12 beats/min, P less than .05) and plasma norepinephrine (106 +/- 48 v 169 +/- pg/mL, P less than .07) and greater ratio of HR.BP double product on ETT/pacing, (141 +/- 33 v 111 +/- 19, P less than .02). The sympathetic nervous tone of group I was low at baseline but there may have been raised alpha/beta-receptor responsiveness to laboratory stresses with concomitant micro/macrovascular constriction at higher oxygen demand.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1632937 TI - Silent myocardial ischemia in patients with essential hypertension. AB - The aim of this study was to determine the significance of the "coronary factor" in patients with essential hypertension (EH). Electrocardiogram Holter monitoring was performed in 61 patients with EH stage II (according to the World Health Organization criteria). Silent, ie, painless ST-segment depression, was found in 34 patients on whom echocardiography, a treadmill test, and transesophageal pacing were performed. In 21 patients with EH and silent ischemia, the examination included 201Tl stress scintigraphy, coronary angiography, and a platelet aggregation test. In 15 patients, catecholamines and beta-endorphins were obtained in blood samples during silent ischemia. 201Tl scintigraphy showed transient defects of perfusion without clearance abnormalities (group I) and with clearance abnormalities (group II). The patients in group I had more severe left ventricular hypertrophy (LVH) and a significantly higher platelet aggregation response to 0.5 mumol/L adenosine diphosphate; one patient in this group had coronary atherosclerosis. LVH and the platelet aggregation response was less pronounced in the patients in group II, but atherosclerotic lesions of a coronary artery were observed in four patients. In both groups, norepinephrine and beta endorphin levels were increased during silent episodes of ischemia. The results suggest that there are different pathogenetic mechanisms of coronary insufficiency in patients with EH, a hypertensive heart, and silent ischemia. PMID- 1632938 TI - Left ventricular mass as a measure of preclinical hypertensive disease. AB - The ability to identify the hypertensive patient who is destined to suffer a morbid or fatal complication in the long presymptomatic phase of this condition, when its natural history would be most subject to amelioration, is limited by the weak relation between the level of blood pressure and the occurrence of complications. Recent research indicates that the level of left ventricular (LV) mass--most conveniently measured by echocardiography--reflects the combined effects of a variety of factors involved in the pathophysiology of hypertension, including obesity, exaggerated blood pressure responses to everyday activity, high sodium intake and blood viscosity, and genetic factors predisposing to hypertension. Prospective studies indicate that LV mass is a stronger predictor of subsequent morbid events and death than blood pressure or other conventional risk factors except age. Preliminary findings of close relations between LV mass and arterial disease and between the change in LV mass during antihypertensive treatment and subsequent events contribute to explaining the strong predictive value of LV mass. Further research is needed to clarify the biologic basis of these observations and to determine whether stratification of hypertensive patients based on their level of LV mass can improve the treatment of hypertension. PMID- 1632939 TI - Evaluation of cardiac performance in hypertension. AB - Myocardial perfusion and left ventricular (LV) diastolic filling were studied in 67 patients with mild to moderate hypertension and left ventricular hypertrophy (LVH). The control group consisted of 28 subjects with no cardiac pathology. LV mass assessed by M-mode echocardiography was obtained in all patients. LV diastolic filling was estimated by pulsed Doppler echocardiography before and after intravenous administration of verapamil (0.145 mg/kg) and contrast ventricular angiography during intracoronary administration of verapamil (1 to 1.5 mg). Myocardial perfusion was estimated by technetium-99m scintigraphy with albumin microspheres and thallium-199 scintigraphy in combination with intravenous dipyridamole. Coronary artery disease was excluded in 42 patients by coronary angiography. Pulsed Doppler echocardiography demonstrated an inverse correlation between the LV mass index and the ratio of peak early to peak atrial velocity (r = -65, P less than .001). Twelve of 20 patients experienced transient "normalization" of LV diastolic filling during intravenous administration of verapamil. In addition, 6 of 22 patients with LVH had an increase in end diastolic volume owing to enhanced segment relaxation of the injected artery during intracoronary administration of verapamil. Myocardial perfusion defects assessed by scintigraphy with albumin microspheres were observed in 8 of 13 patients but in no controls. According to 199T scintigraphy data, myocardial perfusion defects were more common in patients with LVH (P less than .05). Thus, essential hypertension combined with LVH appears to result in severe cardiac dysfunction, which is probably associated with changes in small vessel walls. PMID- 1632940 TI - Chronic hypotension. In the shadow of hypertension. AB - Understanding the causes and treatment of chronic hypotension is of benefit to affected patients and may also shed light on the physiology and genetics of mechanisms of blood pressure control. Symptomatic hypotension (almost always with a blood pressure fall greater than or equal to 20/10 mm Hg) may reflect unrecognized medication effects or a variety of other causes. Autonomic neuropathies include those secondary to diabetes, peripheral autonomic impairment (the Bradbury-Eggleston syndrome), central autonomic impairment (the Shy-Drager syndrome), or newly described gene defects such as dopamine-beta-hydroxylase deficiency (which causes the absence of norepinephrine with an accumulation of dopamine). Baroreceptor dysfunction causes wide swings in blood pressure that are unrelated to posture, whereas a variety of stimuli (cough, micturition, or carotid sinus pressure) may precipitate paroxysmal parasympathetic activation, and sympathetic orthostatic hypotension associated with hypovolemia may occur with mitral valve prolapse or as an idiopathic condition. The differentiation of these and other causes of symptomatic hypotension may in many cases lead to beneficial therapy. PMID- 1632941 TI - Effects of subacute exposure to noise on the noradrenergic innervation of the cardiovascular system in young and aged rats: a morphofunctional study. AB - The effects of subacute noise stress on the noradrenergic pattern and receptor mediated responses were examined in aorta and atria of young and aged rats. Noise exposure increased the density of noradrenergic fibres and responses to the beta adrenergic agonist isoprenaline in the cardiac tissue of young animals. In aged rats, the stressing stimulus markedly increased the maximal response to the alpha agonist on the aortic musculature; on the contrary, a reduced responsiveness to the beta-agonist was observed at the cardiac level, without any noteworthy changes in the noradrenergic pattern in comparison to aged controls. The present results indicate that subacute noise stress induces both morphological and functional modifications of the noradrenergic nervous system and also that after subacute noise stress, morphological changes do not necessarily correspond exactly to functional data; the latter show responses that are more widely differentiated than the morphological ones. PMID- 1632942 TI - Differential effect of guanethidine on dopamine and norepinephrine in rat peripheral tissues. AB - The changes of dopamine (DA) and norepinephrine (NE) were investigated in rat peripheral tissues after guanethidine treatment (50 mg/kg i.p. five days each week) during one week (group 1, n = 10, five injections) and during 2.5 weeks (group 2, n = 8, 13 injections). Guanethidine greatly reduced NE levels in all the analyzed tissues but only partially depleted DA in kidney, bladder, stomach, intestine, lung and liver and in sympathetic ganglia. The differential pattern of changes between DA and NE induced by guanethidine suggests that peripheral DA is distributed in several neuronal or non-neuronal pools, whose presence, nature and contribution varies in the different tissues. Both noradrenergic cell bodies and small intensely fluorescent cells (SIF cells) can contribute to the DA in the superior cervical ganglion. Noradrenergic neurons seem to be the main sources of DA in seminal vesicles, vas deferens, heart and spleen. In addition to noradrenergic nerves, extraneuronal sources could account for a meaningful portion of DA in kidney, gastrointestinal tract, lung and liver. The bladder is the peripheral tissue where DA exhibits the highest resistance to the neurotoxin. Accordingly, these tissues may provide meaningful sources of non-precursor DA pools. PMID- 1632943 TI - The pharmacological effect of citalopram residues in the (S)-(+)-enantiomer. AB - The enantiomers of citalopram and N-demethylcitalopram have been investigated. Based on the inhibition of 5-HT uptake in vitro and the potentiation of 1-5-HTP in vivo the pharmacological activity resides in the (+)-enantiomers (the eutomers*) with the 1-(S) absolute configuration. In the 5-HT uptake test eudismic ratios of 167 and 6.6 are obtained for the enantiomers of citalopram and N-demethylcitalopram, respectively. The pharmacological profile of the eutomers of citalopram and N-demethylcitalopram very much resembles the profile of the respective racemates. PMID- 1632944 TI - Transient reduction of cerebral blood flow leads to longlasting increase in GABA content in vulnerable structures and decreased susceptibility to bicuculline induced seizures. AB - Rats were exposed for 24 min to bilateral clamping of the common carotid arteries (BCCA) in pentobarbital anaesthesia. The GABA content was measured 24 hours, 48 hours, 4 days, 14 days and 3 months after BCCA. In other groups of rats seizures were elicited by i.p. injection of (+)-bicuculline (3 mg/kg) 24 hours, 48 hours, 4 days, 14 days and 3 months after BCCA. Analysis of the GABA content revealed significant increase compared with controls in the hippocampus, frontal cortex and substantia nigra from 24 hours up to 3 months. Bicuculline treatment induced tonic/clonic seizures and status epilepticus in sham operated animals; these effects were drastically diminished at various time points after BCCA. The present results suggest that BCCA produces a longlasting increase in GABA content and as a consequence protection from bicuculline-induced seizures. PMID- 1632945 TI - Biosensors for environmental monitoring. AB - In this article we will outline several biosensor applications which may fill existing technology gaps in the area of environmental monitoring. The requirements for these environmental biosensors, as well as difficulties in commercialization, are also addressed. PMID- 1632946 TI - A lysine dehydrogenase-based electrode for biosensing of L-lysine. AB - An amperometric biosensor for L-lysine based on the recently isolated enzyme lysine dehydrogenase is described. Immobilization of the enzyme onto a platinum electrode is achieved via entrapment within a gelatin support on a cellulose membrane. Anodic detection (at 0.4 V vs. Ag/AgCl) is facilitated by the presence of a redox-mediating ferricyanide ion. The effect of experimental variables such as pH, enzyme loading, applied potential, cofactor and mediator concentrations were evaluated in order to optimize the analytical performance. A detection limit of 7 x 10(-8) M, and linearity up to 7 x 10(-4) M are reported. The fast response permits adaptation for flow injection operation with good precision (RSD = 1.9%) and high sample throughout (40 samples per hour). The high specificity offered by this new enzyme is indicated by the lack of interference by other L-amino acids, alcohols or carbohydrates. PMID- 1632947 TI - Sensitive detection of pesticides using amperometric sensors based on cobalt phthalocyanine-modified composite electrodes and immobilized cholinesterases. AB - The determination of organophosphate and carbamate pesticides was carried out using cobalt phthalocyanine-modified carbon epoxy composite electrodes coupled with acetylcholinesterase or butyrylcholinesterase. Covalent immobilization of enzymes on Immobilon membranes or nylon nets was examined; the highest sensitivity to inhibitors was found for the nylon net containing low enzyme loading and this was subsequently used for the construction of an amperometric biosensor for pesticides. Analyses were done using acetyl- or butyrylthiocholine as substrates; thiocholine produced by hydrolysis in the enzyme membrane was electrochemically oxidized at +300 mV (vs. Ag/AgCl reference). The decrease of substrate steady-state current caused by the addition of pesticide was used for evaluation. With this approach, 1.5 and 8.4 micrograms l-1 of paraoxon and heptenophos, respectively, can be detected in less than 3 min. These detection limits are similar as those obtained when analyses were performed using free cholinesterase and 10 min incubation with inhibitor. PMID- 1632948 TI - Evaluating in vitro and in vivo the interference of ascorbate and acetaminophen on glucose detection by a needle-type glucose sensor. AB - The aim of this work was to assess, in vitro and in vivo, the interference of ascorbate and acetaminophen on glucose measurements by a needle-type glucose sensor detecting hydrogen peroxide generated during the enzymatic oxidation of glucose, and to ascertain whether the protection against interference by the membranes used in the construction of the electrode is feasible. The oxidation of ascorbate and acetaminophen on a platinum electrode set at a 650 mV potential yielded a current representing 75 +/- 5% and 25 +/- 6% of that generated by the oxidation of an equimolar concentration of hydrogen peroxide, respectively. The bias introduced by the presence of 100 mumol l-1 ascorbate on the reading of 5 mmol l-1 glucose by the complete sensor (electrode + membranes) would be minimal (approximately 0.4 mmol l-1). By contrast, the bias introduced by 200 mumol l-1 of acetaminophen (a plasma concentration easily reached in clinical practice) was about 7 mmol l-1. The sensor was implanted subcutaneously in anaesthetized rats (n = 3). Using the current generated in the presence of a plasma acetaminophen concentration of about 200 mumol l-1 for glucose monitoring would lead to a major underestimation (approx. 6 mmol l-1) of subcutaneous glucose concentrations. PMID- 1632949 TI - Electrochemically modulated optrode for glucose. AB - One of the problems with fibre-optic sensors is the difficulty of finding reversible indicator reagents. This is a particular problem for fibre-optic glucose sensors. The development of an electrochemically modulated fibre-optic probe or optrode has been proposed as a convenient solution. Here the indicator reagent is regenerated electrochemically. In this work a design is proposed that offers considerable advantages in practical applications. In particular, it can be used in the same way as conventional optrodes. The optimization of working parameters and the application of the optrode to flow analysis under steady-state and flow-injection conditions is described. PMID- 1632950 TI - Glucose biosensor based on carbon black strips. AB - Amperometric biosensors for the determination of beta-D-glucose have been constructed. They were based on a porous matrix of carbon blacks--'Ketjenblack' (KB) and 'Shawinigan black' (SB) wet-proofed with polytetrafluorethylene. Glucose sensitive elements were prepared by subsequent adsorptional immobilization of 1,1'-dimethylferrocene (DMFc) and nickel-ocene (Nc) on 'Shawinigan black' or tetracyanoquinodimethane (TCNQ) on 'Ketjenblack' together with Penicillium chrysogenum glucose oxidase. Maximum surface concentrations of DMFc, Nc and TCNQ on carbon black electrodes were 95, 116 and 151 nmol cm-2. The biosensor based on KB and TCNQ (KB-TCNQ biosensor) could be used at a potential of 0.5 V (vs. Ag/AgCl reference electrode) in the concentration range up to 7 mM. This biosensor possessed an approximately ten times higher sensitivity than the ones based on SB and DMFc (SB-DMFc biosensor) and on SB and Nc (SB-Nc biosensor) which acted at 0.3 V and 0.05 V, respectively. The biosensors were suitable for practical use longer than one week. PMID- 1632951 TI - Immobilization of flavoproteins on silicon: effect of cross-linker chain length on enzyme activity. AB - The effect of cross-linker chain length on the activities of choline oxidase (ChO) and glucose oxidase (GOx) immobilized on oxidized silicon wafers has been investigated for the cross-linkers N-succinimidyl 4-maleimido-butyrate (GMBS) and N-succinimidyl 6-maleimidocaproate (EMCS). Enzyme activities were determined with an indirect fluorometric assay based on the production of hydrogen peroxide. Immobilization of ChO or GOx onto oxidized silicon with either cross-linker resulted in an 86-99% loss in enzymatic activity relative to the soluble form of the flavoprotein. However, the different cross-linkers had distinctly different effects on enzyme activity: EMCS-immobilized GOx was four times more active than GMBS-immobilized GOx; EMCS-immobilized ChO had a sevenfold higher activity than GMBS-immobilized ChO. PMID- 1632952 TI - Amperometric enzyme electrode for determination of theophylline in serum. AB - This paper describes an amperometric enzyme electrode for the rapid determination of theophylline in serum. The method is based on the catalysed oxidation of theophylline by the haem-containing enzyme theophylline oxidase. Results are presented for two approaches. First, ferrocene monocarboxylic acid was used as a mediator. The second-order rate constant was 1.1 x 10(3) 1 mol-1 s-1. Secondly, the organic conducting salt NMP.TCNQ was used to construct enzyme electrodes. These electrodes were employed for the rapid (60 s) measurement of theophylline in serum at a working potential of +100 mV versus Ag/AgCl. Linear calibration curves were obtained over the clinically relevant range (y = 0.13x + 0.22, n = 8). Caffeine, theobromine and 3-methylxanthine at levels up to 100 mg l-1 do not interfere and 1-methylxanthine shows cross-reactivity at concentrations greater than 50 mg l-1. PMID- 1632953 TI - Effects of lengthened immobilization on functional and histochemical properties of rabbit tibialis anterior muscle. AB - The imposition of long-term lengthened immobilization on rabbit tibialis anterior (TA) muscles resulted in rapid increases in slow oxidative (SO) fibre number. After 2 weeks, SO number had increased 2-fold and was 5 times greater after 6 weeks immobilization. There were also fibre-type-specific effects on SO, fast oxidative glycolytic (FOG) and fast glycolytic (FG) fibre areas. Twitch strength was unchanged throughout immobilization whilst production of tetanic tension was impaired during the initial period but had returned to control levels by 6 weeks. Twitch contraction times and isometrically determined rates of rise and relaxation were largely unaffected by immobilization despite the marked increase in expression of slow myosin. The change in phenotypic expression of the lengthened TA was not attributable to chronically increased levels of activation since integrated EMG activity was unchanged from control values throughout the immobilization period. Thus it is suggested that a chronic increase in tension consequent on the lengthening procedure is a potent stimulus for fast-to-slow myosin transformation. PMID- 1632954 TI - Diversity and homogeneity within endplates associated with physiologically identified static gamma-axons in cat tenuissimus muscle. AB - The terminations of static gamma-axons on chain fibres may be associated with a muscle surface contour thrown into complex folds at one extreme, ranging through lesser degrees of folding to being apparently uninfluenced by the presence of the terminals. The folding is not necessarily confined to the postsynaptic membrane. As a quantitative indicator of the degree of folding seen in cross-sections, the perimeters of the two halves of the intrafusal fibre with, and without the ending were compared. Both complexity of endplate structure and an undifferentiated appearance could co-exist within individual endings (of six static gamma-axons on thirteen chain fibres), associated with axons that supplied only chain fibres in the spindle isolated. (It should be noted, however, that the type of intrafusal fibres innervated by a particular axon was definitively identified only for the spindle isolated.) Endings of three other static gamma-axons on six chain fibres had a more homogeneous and less complex endplate structure; these supplied bag2 fibres in addition to the chain fibres and their endplates on the bag2 fibres were less folded than those of three axons which supplied bag2 fibres only. A sensory inhibitory influence on folding was not apparent because complexly folded endplates on chain fibres lay close (less than 500 microns) to sensory endings. All the endings studied were functional. In our experimental conditions all nine static gamma-axons which innervated chain fibres, alone, or together with a bag2 fibre, drove the Ia afferent at some stimulus frequencies; none of the three static gamma-axons innervating bag2 fibres alone caused driving at any frequency. These findings are discussed in relation to the concept of a dynamic remodelling of ending structure during life, to the relationship between the motor axon and the intrafusal fibre it innervates, and to the possibility that subgroups of static gamma-motoneurones might exist which could release different amounts of the trophic substances responsible for moulding the endplate structure. PMID- 1632955 TI - Reflex vascular responses to changes in left ventricular pressures, heart rate and inotropic state in dogs. AB - Dogs were anaesthetized with chloralose, artificially ventilated and the chests widely opened. Left ventricular mechanoreceptors, including those in or near the coronary arteries, were stimulated by changing the pressure in the aortic root. The pressures distending the left atrium and the aortic and carotid baroreceptors were controlled. Reflex vascular responses were assessed from changes in perfusion pressures to a hind limb and to the rest of the systemic circulation, which were perfused independently at constant flows. Physiological increases in peak left ventricular and coronary arterial pressures resulted in vasodilatation in both regions. These responses were not influenced by changes in the heart rate. Stimulation of the left cardiac sympathetic nerves resulted in increases in peak ventricular pressure and in the maximal rate of change of pressure (dP/dtmax). This also resulted in increases in perfusion pressures (vasoconstriction) at all levels of peak ventricular pressure although there was little effect on the responses to changes in ventricular pressure. Sympathetic stimulation had little effect on the relationship between perfusion pressures and aortic root pressure. Increases in ventricular filling also resulted in vasoconstriction at all levels of peak ventricular pressure. Increases in filling, however, did not affect the relationship between either perfusion pressure and aortic root pressure. Conversely, decreases in left ventricular filling, by bypassing some of the left atrial blood, resulted in vasodilatation at all levels of peak ventricular pressures but had no effect on the perfusion pressures at any aortic root pressure. The combination of sympathetic stimulation with decreased ventricular filling resulted in little effect on perfusion pressures or on their responses to changes in either aortic root or ventricular systolic pressures. We conclude that the vascular responses to stimulation of left ventricular mechanoreceptors are not enhanced by sympathetic stimulation, decreases in ventricular filling or the combination of the two. The apparent effects of each of these interventions alone on the relationships between perfusion pressures and ventricular, but not aortic root, pressure, could be explained if the receptors responsible were sensitive more to changes in aortic root and coronary arterial pressures than to pressure changes in the ventricle itself. PMID- 1632956 TI - The effects in the rat of two fragments of parathyroid hormone-related protein on uterine contractions in situ. AB - Synthetic parathyroid hormone fragment PTH(1-34) has been reported recently to inhibit uterine contractions stimulated by a variety of agonists. We have studied the effect in this system of the parathyroid hormone-related protein fragment PTHrP(1-34) which shows 60% homology with PTH over the first thirteen amino acid residues. The effects of two different PTHrP fragments on acetylcholine stimulated uterine contractions in vitro were studied. Whereas synthetic hPTHrP(75-86 amide) (10(-9)-10(-7) M) was without effect, synthetic hPTHrP(1-34) (10(-9)-10(-7) M) was capable of inhibiting, in a dose-related fashion, uterine muscle contractions precontracted with 10(-6) M-acetylcholine. In a second series of experiments the bovine PTH(3-34) fragment itself was shown to have no stimulatory effect on acetylcholine-stimulated contractions. Also this fragment in an equimolar concentration (10(-7) M) failed to antagonize the effects of PTHrP(1-34) on acetylcholine-stimulated uterine contractions. However, a 100-fold excess molar concentration of bPTH(3-34) (10(-6) M) completely abolished the inhibitory action of hPTHrP(1-34) (10(-8) M) on acetylcholine-stimulated uterine contractions. These results clearly show that the inhibitory action of PTH(1-34) and PTHrP(1-34) on uterine contractions depends on the integrity of the amino terminal region of the molecule. PMID- 1632957 TI - Segmental differences of short-chain fatty acid transport across guinea-pig large intestine. AB - Unidirectional fluxes of short-chain fatty acids (SCFAs) were measured under short-circuit current conditions across guinea-pig caecum, proximal and distal colon. Fluxes increased linearly with concentration. In the caecum with equal concentrations on both sides of the mucosa the serosal-to-mucosal (sm) fluxes were nearly twice the mucosal-to-serosal (ms) fluxes for all SCFAs; in the distal colon ms fluxes were always higher than sm fluxes. Thus, in the caecum the net effect was secretion while in the distal colon net absorption occurred. In caecum, ms fluxes decreased with chain length while sm fluxes were similar for the three fatty acids, acetic, propionic and butyric acid. In the distal colon both unidirectional fluxes increased with chain length. Fluxes across the mucosa of the proximal colon were intermediate to those in caecum and distal colon. A paracellular transport of short-chain fatty acids is not present. The results indicate that other processes are involved in transcellular transport of SCFA besides non-ionic diffusion. PMID- 1632958 TI - Growth-related change in specific force but not in specific power of rat fast skeletal muscle. AB - The effect of growth on the dynamic performance of rat medial gastrocnemius muscle was studied. From approximately 1.5 to 5 months of age specific force increased by 18%. Reductions were found in both optimal stimulation frequency (from 120 to 100 Hz) and optimal shortening velocity (by 16%) indicating that the fibres became slower. Specific power did not change during growth but was obtained at a lower shortening velocity. Possible mechanisms for the observed changes are discussed. PMID- 1632959 TI - Evidence for involvement of nitric oxide in the non-adrenergic non-cholinergic (NANC) relaxation of human lower oesophageal sphincter muscle strips. AB - Electrical field stimulation of circular muscle strips from human lower oesophageal sphincter reveals a predominant relaxation response. This relaxation is non-adrenergic non-cholinergic (NANC). The nitric oxide synthesis-blocking agent N omega-nitro-L-arginine (10-100 microM) reduces or abolishes this NANC relaxation, suggesting involvement of nitric oxide in the response. PMID- 1632960 TI - Evidence for simultaneous bidirectional fluid flux across synovial lining in knee joints of anaesthetized rabbits. AB - A recent model predicted a local synovial circulation of extravascular fluid in which capillary filtrate entered a joint cavity and fluid simultaneously drained out of the cavity via intercellular pathways distant from capillaries. Here, solutions of albumin (10-250 g l-1) were infused continuously into the knee joint cavity in fifteen anaesthetized rabbits at 3-18 cmH2O pressure and steady-state net trans-synovial flow was recorded. The intra-articular fluid collected after 15-30 min was substantially diluted despite a sustained net efflux from the cavity. This supports the prediction that net efflux comprises an influx of low protein plasma ultrafiltrate and a larger efflux of joint fluid. PMID- 1632961 TI - Involvement of carbonic anhydrase in ammonia flux across rumen mucosa in vitro. AB - Carbonic anhydrase activity in mucosa of the sheep rumen wall was completely inhibited by acetazolamide and ethoxyzolamide. This inhibition significantly reduced ammonia flux across mucosal discs in vitro but was ineffective if short chain fatty acids were present in the bathing solution. The findings are discussed in relation to the mechanism of ruminal ammonia absorption. PMID- 1632962 TI - Appearance of phloridzin-sensitive glucose transport is not controlled at mRNA level in rabbit jejunal enterocytes. AB - Glucose uptake by rabbit intestine has been shown to be confined to the upper two thirds of jejunal villi. Inhibition by phloridzin shows most of this transport to take place through the Na(+)-glucose linked transporter (SGLT1). Parallel measurements on the other hand show SGLT1 mRNA expression to increase rapidly as enterocytes reach the crypt-villus junction. Levels of SGLT1 mRNA then remain elevated in all villus enterocytes. These results provide direct evidence that SGLT1-mediated glucose transport is subject to post-transcriptional control. PMID- 1632963 TI - Evidence for presynaptic depression of monosynaptic excitation in neonatal rat motoneurones by (1S,3S)- and (1S,3R)-ACPD. AB - Both the (1S,3S) and (1S,3R) stereoisomers of 1-aminocyclopentane-1,3 dicarboxylate (ACPD), but not the (1R,3R) or (1R,3S) isomers, potently depress the fastest (presumed monosynaptic) component of dorsal root-evoked ventral root potentials in hemisected isolated spinal cord of the newborn rat. This effect is not due to antagonism of known excitatory amino acid (EAA) receptors on motoneurones and may reflect an action of the two ACPD isomers at presynaptic EAA receptors of the L-2-amino-4-phosphonobutyrate (L-AP4) type. PMID- 1632964 TI - Horizontal integration and cortical dynamics. AB - We have discussed several results that lead to a view that cells in the visual system are endowed with dynamic properties, influenced by context, expectation, and long-term modifications of the cortical network. These observations will be important for understanding how neuronal ensembles produce a system that perceives, remembers, and adapts to injury. The advantage to being able to observe changes at early stages in a sensory pathway is that one may be able to understand the way in which neuronal ensembles encode and represent images at the level of their receptive field properties, of cortical topographies, and of the patterns of connections between cells participating in a network. PMID- 1632965 TI - Pathway selection by ectopic motoneurons in embryonic zebrafish. AB - Primary motoneurons in embryonic zebrafish innervate cell-specific muscles. During pathfinding, motoneuronal growth cones encounter three distinct regions: a common pathway, a choice point, and separate cell-specific pathways. To learn whether the order in which these regions are encountered influences pathway choice, we transplanted individual motoneurons to the choice point region. These cells selected their appropriate cell-specific pathways. Thus, the sequence in which pathway regions are encountered may not be important for accurate path finding, and the cell-specific pathways may be delineated by distinct cues that individual growth cones recognize. Moreover, these cues are unlikely to be general ones, since primary sensory neurons transplanted to the same location do not extend growth cones along the motoneuronal pathways. PMID- 1632966 TI - Temporal limits on the rise in postsynaptic calcium required for the induction of long-term potentiation. AB - The induction of long-term potentiation (LTP) in hippocampal CA1 pyramidal cells requires a rise in postsynaptic intracellular Ca2+ concentration ([Ca2+]i). To determine the time for which Ca2+ must remain elevated to induce LTP, the photolabile Ca2+ buffer diazo-4 was used to limit the duration of the rise in postsynaptic [Ca2+]i following a tetanus. The affinity of diazo-4 for Ca2+ increases approximately 1600-fold upon flash photolysis, permitting almost instantaneous buffering of [Ca2+]i without disturbing resting [Ca2+]i prior to the flash. Photolysis of diazo-4 1 s following the start of the tetanus blocked LTP, while delaying photolysis for more than 2 s had no discernible effect on LTP. Photolyzing diazo-4 at intermediate delays (1.5-2 s) or reducing photolysis of diazo-4 often resulted in short-term potentiation (STP). These results indicate that a tetanus-induced rise in postsynaptic [Ca2+]i lasting at most 2 2.5 s is sufficient to generate LTP. Smaller increases or shorter duration rises in [Ca2+]i may result in STP. PMID- 1632967 TI - The amyloid protein precursor of Alzheimer's disease is a mediator of the effects of nerve growth factor on neurite outgrowth. AB - The beta A4 protein, the major component of the amyloid deposition characterizing Alzheimer's disease, derives from the amyloid protein precursor (APP), an integral membrane protein with soluble derivatives. The function of APP is unknown. Both soluble and membrane-associated human brain APP (10(-10) M) significantly increased (P less than 0.025) neurite length and branching in pheochromocytoma PC12 cells, but did not affect the number of neurites per cell. At higher concentrations, APP was cytotoxic, with a half-maximal concentration of 5 x 10(-9) M. Nerve growth factor (NGF) is known to affect APP expression in vivo and in vitro. Antibodies to APP specifically diminished the effects of NGF on neurite length and branching. Thus APP may act to mediate neurite outgrowth promotion by NGF. PMID- 1632968 TI - Generation and migration of cells in the developing striatum. AB - The development of the rat striatum was investigated using a combination of two histochemically distinguishable retrovirus vectors. Using this method, it was possible to identify clonal boundaries within the embryonic striatum and thus determine patterns of proliferation, migration, and some lineal relationships. Several novel aspects of striatal histogenesis were discovered. Striatal progenitor cells do not exhibit a stem cell pattern of division between embryonic day 15 (E15) and E19; a progenitor-progeny relationship appears to exist for ventricular zone and subventricular zone (SVZ) cells; striatal progenitors produce a variety of clone types; some SVZ cells migrate radially, and some migrate tangentially within the SVZ; and radial glia and presumptive neurons can occur in the same clone. PMID- 1632969 TI - Involvement of neuronal cell surface molecule B2 in the formation of retinal plexiform layers. AB - The B2 molecule is a 220 kd neuronal cell surface protein of Xenopus, recognized by monoclonal antibody B2 (MAb B2). Immunohistochemistry using MAb B2 revealed that the B2 molecule was expressed in both the inner and outer plexiform layers within the neural retina. During development of the neural retina, the B2 molecule first appeared at stages 35/36 in the newly formed plexiform layers. When embryonic eyes were cultured in the presence of anti-B2 antiserum (Fab fragments), the formation of the retinal plexiform layers was impeded. These data suggest that the cell surface molecule B2 plays a role in the development of retinal plexiform layers. PMID- 1632970 TI - A partial cDNA sequence of the Dlx-2 cDNA. PMID- 1632971 TI - Breast cancer and smoking, vodka drinking and dietary habits. A case-control study. AB - The relationship between cigarette smoking, vodka drinking and consumption of 44 food items typical of the Polish diet were analysed in a case-control study in Cracow, Poland, among 127 cases of breast cancer and 250 controls randomly selected from the general population. Cigarette smoking was not significantly influencing the breast cancer risk. Compared with never-drinkers, the habit of vodka drinking 20 years earlier significantly increased breast cancer risk in women below 50 years of age (multivariate OR was 4.4 with 95% CI 1.6-12.4). Frequent consumption of boiled vegetables 20 years earlier (greater than 3 times per week) was associated with a decreased risk of breast cancer in women aged 50 years and more (multivariate OR was 0.4 with 95% CI 0.2-0.8). PMID- 1632972 TI - Clinical examination, mammographic findings and cytological diagnosis in patients with breast disorders. Results of 9 years' follow-up. AB - In January through March 1978, 482 consecutive patients sought advice and examination for different kinds of breast disorders at the Breast Unit of Radiumhemmet; 171 of them (32.8%) came without any prior known medical consultation. All patients were seen by a doctor and examined clinically; 385 underwent mammography and 196 fine-needle aspiration for cytology. Combined clinical and mammographic examination showed an estimated specificity with respect to 'breasts with no need of follow-up' of 77%. The corresponding sensitivity was 88%. Fine-needle aspirations showed an estimated specificity and sensitivity of 96% and 88% respectively. In the total material 26 malignant cases were found, of which 16 cancers were detected at the first examination. During a follow-up period of nine years, 10 additional breast cancers were found in the national cancer registry. This number could be compared to the expected number of 6.6 (SIR 1.52, 0.73-2.79) breast cancer cases if the studied women had had the same standardized incidence as the total female Swedish population. The mean number of visits to the Breast Unit was 1.6 for the 466 patients with benign disorders, of whom 322 had no need of follow-up. The mean follow-up time for these 482 patients was 113 days. During the follow-up time, 22 patients died. Ten patients, one of them with a breast cancer diagnosed, emigrated. PMID- 1632973 TI - Tumors after radiotherapy for thyroid cancer. A case-control study within a cohort of thyroid cancer patients. AB - A case-control study of Swedish thyroid cancer patients was conducted to evaluate the possible influence of 131I treatment and external radiotherapy on the risk of developing a subsequent cancer. Both cases and controls derived from a cohort of Swedish thyroid cancer patients treated with 131I (n = 834) or by other means (n = 1,121). Thirty-six breast, 13 stomach, 12 kidney, and 5 bladder cancers were found more than 2 years after 131I treatment/thyroid cancer diagnosis. Individual, absorbed dose in the organs was calculated by using ICRP tables, administered activity of 131I, and 24-h 131I uptake. In studying the effect of 131I and external radiotherapy no statistically significant dose-response relationships were found for cancers of the breast, stomach, bladder or kidney. When the absorbed dose from 131I was analyzed separately the risks remained essentially the same. The present follow-up time and the relatively low absorbed dose that the patients received from 131I and external radiotherapy necessitate studies with a longer follow-up time or a larger patient material before more firm conclusions can be made. PMID- 1632974 TI - Protein tyrosine kinase activity in human thyroid papillary carcinoma. AB - We compared the protein tyrosine kinase (PTK) activity in the acytosolic and particulate fractions of homogenates obtained from 10 papillary thyroid adenocarcinomas with the corresponding activity in 10 specimens from adjacent normal thyroid tissue and 8 follicular adenomas. The cytosolic PTK activity of papillary adenocarcinomas was significantly elevated compared to normal and adenoma tissue. The particulate PTK activity was also significantly elevated in the papillary adenocarcinomas. The cellular distribution of PTK activity (cytosolic activity in percentage) in normal thyroid tissue, adenomas, and papillary adenocarcinomas showed no significant difference (62%, 64% and 63% respectively). These findings indicate that elevated cytosolic PTK activity may be a potentially useful marker for papillary thyroid carcinoma. PMID- 1632975 TI - Soluble interleukin-2 receptor levels in patients with malignant melanoma and renal cell cancer. AB - Soluble interleukin-2 receptor (sIL-2R) levels were measured in sera from 33 patients with metastatic malignant melanoma and 14 patients with metastatic or advanced renal cell cancer. Significantly elevated levels were found in both groups compared to 30 healthy controls. No correlation was found between the levels of sIL-2R and clinical parameters such as disease-free interval and tumour burden. Neither was there any correlation between receptor-levels and survival. This contrasts with the observations in lymphoma patients, but is in accordance with findings in other solid tumours. sIL-2R is possibly a marker of the host immune response to the tumour, but further investigations are needed to see if it has any predictive value concerning prognosis or response to immune therapy. PMID- 1632976 TI - Serum tumour necrosis factor alpha levels in benign and malignant lesions of the endometrium in postmenopausal women. A preliminary study. AB - Tumour necrosis factor alpha (TNF alpha) concentration was determined by a solid phase immunoradiometric assay in sera of 20 healthy postmenopausal women (reference group), 10 women suffering from postmenopausal bleeding with histologically confirmed cystic glandular hyperplasia, and 10 postmenopausal bleeding patients with histologically confirmed endometrial adenocarcinoma. In cases of endometrial adenocarcinoma serum TNF alpha (157.6 +/- 28 pg/ml) was found to be significantly higher than in controls (80.6 +/- 4.1 pg/ml). The rate of abnormally high values of serum TNF alpha increased with advancing stage of the disease. On the other hand, serum TNF alpha level in cases of endometrial hyperplasia (38 +/- 6 pg/ml) was significantly lower than in healthy individuals. It seems that the rise of serum TNF alpha in cases of endometrial carcinoma represents a possible mechanism of immune surveillance. The results suggest clinical usefulness of serum TNF alpha estimations for the differential diagnosis of benign and malignant lesions of the endometrium in women with postmenopausal bleeding. PMID- 1632977 TI - Crude isolation of DNA from unselected human pancreatic tissue and amplification by the polymerase chain reaction of Ki-ras oncogene to detect point mutations in pancreatic cancer. AB - Human pancreatic tissue obtained during surgery was divided into two samples, one stored in formalin for histology and the other frozen directly for DNA studies. A small bit of the frozen tissue was excised without prior differentiation of malignant from non-malignant tissue and crude DNA prepared. The DNA was used to amplify the Ki-ras oncogenes with the polymerase chain reaction (PCR) using primers for codons 12, 13 and 61. The PCR products were hybridized with oligonucleotides to detect mutations in these codons. No mutations were seen in patients histologically free from pancreatic cancer, having cancer of the papilla of Vater or endocrine pancreatic cancer. In the 9 cases of pancreatic cancer, point mutations were detected in codon 12 in 7 cases and in codon 13 in one patient. Thus, the PCR technique can be used to detect point mutations in Ki-ras oncogenes even in crude DNA without selection of malignant from non-malignant tissue. PMID- 1632978 TI - Droloxifene--a new anti-estrogen. A phase II study in advanced breast cancer. AB - Twenty-six patients with advanced breast cancer were treated with a new anti estrogen, Droloxifene (3-hydroxy-tamoxifen). They had all used tamoxifen either in the adjuvant or the advanced situation. The dose schedule was 100 mg orally daily. Partial remissions were observed in 4 (15%) of the patients, and in another 5 patients stable disease (greater than 24 weeks of duration) was observed. Three of the responders were resistant to tamoxifen. Fourteen of the 26 patients had no side-effect. In 2 patients therapy had to be stopped due to fatigue. Droloxifene seems to be an interesting new anti-estrogen which should be further exploited. PMID- 1632979 TI - Interferon combined with irradiation in the treatment of operable head and neck carcinoma. A pilot study. AB - Twenty-two patients with operable head and neck cancer were randomized to receive natural leukocyte alpha interferon (IFN) and radiotherapy, or radiotherapy alone (control) before operation. IFN was administered at 6 MU i.m. daily for 4 weeks and thereafter 3 times per week for 2 months. IFN treatment was introduced simultaneously with radiotherapy (2 Gy daily, 5 fractions per week). The preoperative dose was 30-32 Gy. Tumor response and side-effects were registered. The patients underwent radical surgery 3 weeks after the preoperative irradiation, followed by postoperative irradiation with 22-32 Gy. After preoperative treatment there were one complete response and 4 partial responses among 10 patients receiving IFN and 2 partial responses among 12 patients treated with irradiation alone. No difference in survival was demonstrated between the 2 groups. In the histologic examination of the surgical samples malignant cells were found in 6 of the IFN patients and in 8 of the control patients. The IFN patients had considerably more pronounced mucosal radiation reactions than the controls. The accrual of patients to the study was discontinued due to the side effects. PMID- 1632980 TI - Radiobiological cell survival models. A methodological overview. AB - A central issue in clinical radiobiological research is the prediction of responses to different radiation qualities. The choice of cell survival and dose response model greatly influences the results. In this context the relationship between theory and model is emphasized. Generally, the interpretations of experimental data depend on the model. Cell survival models are systematized with respect to their relations to radiobiological theories of cell kill. The growing knowledge of biological, physical, and chemical mechanisms is reflected in the formulation of new models. The present overview shows that recent modelling has been more oriented towards the stochastic fluctuations connected to radiation energy deposition. This implies that the traditional cell survival models ought to be complemented by models of stochastic energy deposition processes and repair processes at the intracellular level. PMID- 1632981 TI - Application of radiation effect models in combined external and intracavitary radiotherapy of carcinoma of the uterine cervix. AB - A retrospective analysis of 291 patients with cancer of the uterine cervix treated with a combination of external and intracavitary radiotherapy was carried out. Patients were treated with an external radiotherapy dose of 45 Gy in 20 fractions, 5 fractions per week, or 42 Gy in 14 fractions, 3 fractions per week. For brachytherapy the total dose was 24 to 32 Gy at a dose rate of 1.4 to 2.2 Gy per hour. Treatment results in terms of survival, local disease-free survival and complication rates were compared with cumulative radiation effect (CRE) and extrapolated response dose (ERD) values for point A (CRETA and ERDTA respectively) and for rectum (CRETr and ERDTr respectively). CRETA and ERDTA values did not significantly correlate with local disease-free and survival rates. Correlations of CRETA and ERDTA with overall complication rate and with rectal complication rate (p-value less than 0.025) were good. No significant correlation was observed between CRETr or ERDTr and overall complication rate and rectal complication rate. In order to limit grades II and III rectal complications to acceptable level, in combined external and intracavitary treatment, CRETA and ERDTA values of less than 2,500 and 93 respectively are suggested. PMID- 1632982 TI - Combined radiotherapy and surgery in the treatment of neck node metastases from squamous cell carcinoma of the head and neck. AB - A prospectively recorded series of 107 patients with clinical neck node metastases from head and neck squamous cell carcinomas, treated in 1983-1988, and with initial local control, is evaluated. Eighty-eight patients received preoperative, and were operated 4-6 weeks after radiotherapy, and 19 received postoperative radiotherapy. Forty-four of the neck specimens in the preoperatively treated patients showed vital tumor tissue, 7 with positive and 37 with negative resection margins. Nine of the latter 37 patients died due to regional recurrence. Twenty-three of the preoperatively treated patients had no palpable residual tumor following radiotherapy, but histological examination showed vital tumor tissue in five, of whom two had N1 neck disease. The overall regional failure rate was 19%. Eleven patients (10%) died from local recurrence and 11 from distant metastases. Forty-one patients (38%) are alive without evidence of disease and three (3%) alive with disease (mean observation time 30 months). Combined treatment is recommended for all cases of neck node metastases. PMID- 1632983 TI - Effects of glucan on the reticuloendothelial system and on the development of tumors in 90Sr-exposed mice. AB - A series of experiments was conducted to examine the effect of glucan on the reticuloendothelial system (RES) and on the development of 90Sr-induced osteosarcomas and malignant lymphomas in CBA/S mice. Glucan demonstrated a strong RES-stimulating effect, as evidenced by a dose-related increase in lysozyme levels in the plasma and an enlargement of the liver and spleen. Weekly injections of glucan between 150 and 250 days after exposure to 90Sr suppressed the actuarial appearance of the fibroblastic type of osteosarcomas and stimulated the emergence of malignant lymphomas. Glucan itself had no tumorigenic effect in mice not exposed to 90Sr. PMID- 1632984 TI - Normal tissue reactions in mice after combined treatment with metoclopramide and ionizing radiation. AB - We have previously shown that metoclopramide potentiates the effect of ionizing radiation and cisplatin treatment of human squamous cell carcinomas from the head and neck region xenografted to nude mice. In the present tumor study, the dose scheduling of metoclopramide in combination with radiation was evaluated, and metoclopramide was shown to be most effective in potentiating the cytotoxic effect of radiation when administered one hour before radiation. The effect of radiation in combination with metoclopramide on normal tissue was also studied in two well-established models. Acute skin reactions to radiation exposure were studied in 129-type mice, and metoclopramide did not enhance the acute skin reaction in this in vivo model. Survival after whole body irradiation was studied in heterozygote Balb/c nu/+ mice as a measure of bone marrow toxicity. Metoclopramide was not found to affect the LD50/30 in this in vivo model. The absence of potentiation of radiation damage to normal tissue in these animal studies, makes metoclopramide an interesting possibility for future clinical evaluation. PMID- 1632985 TI - Metastasis in the male breast from a lung adenocarcinoma. PMID- 1632986 TI - Genetic mapping and biochemical characterization of suppressor mutations sukA and sukB for a dnaK7(Ts) mutation of Escherichia coli K-12. AB - Temperature-resistant pseudorevertants were isolated from a dnaK7(Ts) mutant of Escherichia coli K-12. Two of these pseudorevertants were shown to carry suppressor mutations, sukA and sukB, respectively. Genetic mapping by conjugation and P1-transduction revealed that these suppressor mutations were located at two distinct sites between 76 and 77 min close to the suhA and rpoH genes. Labeled cellular proteins were extracted from suppressor mutants grown at various temperatures and subjected to SDS-gel electrophoresis. Autoradiograms of the gels indicated that these suppressor mutations each resulted in increased synthesis of the heat shock protein Lon (an ATP-dependent protease, La) at both permissive and nonpermissive temperatures. PMID- 1632987 TI - [Revista Portuguesa de Cardiologia. Quality and prestige to the service of cardiovascular medicine]. PMID- 1632988 TI - [Pharmaceutical companies as sponsors of clinical trials--advantages and limitations]. AB - The therapeutic progress achieved in the second half of this century was made possible only due to the interest taken by the pharmaceutical industry in the research field. It can be considered as the primum movens of the therapeutic revolution which has strongly benefited the humanity in these last decades. The clinical trials of new drugs constitute an integral part of the pharmaceutical and medical research. However its complexity and the costs involved make its execution impossible without the help or sponsorship of the pharmaceutical firms. Even in the more advanced countries it would be unthinkable that clinical trials could be carried out without the assistance of the pharmaceutical industry. The sponsorship by the pharmaceutical firms turns the relationship doctor-firm into a symbiotic association as both the parties reap benefits thereof: the physician because he is able to satisfy his inquisitiveness and his interest for the clinical research and the pharmaceutical firm because through these trials it will collect the information it requires. Besides having to bear the expenses inherent to the research, the sponsoring firms equally contribute for other pursuits usually of academical character and of interest to the investigator. Therefore it is not rare that these firms assume the costs of presence of these investigators in scientific meetings or to contribute for the arrangements of such meetings or even subsidise the acquisition of the equipment for the hospital services, etc.--measures which in countries with poor investments in research sector, such as Portugal, may constitute the only possibility to be carried out.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1632989 TI - [Surgical treatment of ventricular septal defect in the first year of life]. AB - Forty six infants with a large ventricular septal defect (VSD) underwent surgical treatment during the first 12 months of life. Forty three patients ranging in age from 3 to 12 months (mean age 10.4 months) and weighting from 3.0 to 8.2 kg (mean weight 6.8 kg) had primary surgical closure of their VSD. All infants were below the third percentile for weight preoperatively. In 40 patients (93%) the defect was closed through the right atrium. Three patients (7.0%) died in the early postoperative period. Surgically induced heart block occurred in one patient (2.3%). Late results were assessed in 29 surgical survivors (mean follow-up 26 months). There was no late mortality. Relief of congestive heart failure was prompt in all patients following closure of VSD. Right bundle branch block with left anterior hemiblock developed in 5 patients (17.2%), and right bundle branch block alone in 10 patients (34.5%). Three patients (mean age 4.3 months, mean weight 2.7 kg) underwent initial palliative pulmonary artery banding (PAB). There were no operative or late mortality. Closure of VSD and pulmonary artery debanding was performed in two of these patients, with no mortality. Prior to intracardiac correction the pulmonary artery pressure distal to the band was normal; no band related complications were found. Early primary closure is the treatment of choice for symptomatic infants with large VSDs. In particular circumstances, however, PAB may provide effective palliation. PMID- 1632990 TI - [Echocardiographic assessment of interventricular septal defect corrected during the first year of life]. AB - OBJECTIVE: To evaluate the medium term results of surgical closure of ventricular septal defect (VSD) performed during the first year of life, using echocardiography (echo). MATERIAL AND METHODS: We studied prospectively 29 patients aged from 17 to 68 months (mean = 37) who underwent surgical closure of perimembranous VSD during the first year of life. The postoperative follow-up time ranged from 6 to 60 months (mean = 26). Fifteen age-matched normal children were used as a control group in evaluating the left ventricular (LV) systolic function. The echo study included: 1) the assessment of LV systolic function using the shortening fraction, ejection fraction, pre-ejection to ejection time ratio (PET/ET), aortic flow acceleration time, acceleration to ejection time ratio, mean aortic flow acceleration; 2) detection and quantification of residual VSD as well as tricuspid and or aortic regurgitation; 3) determination of right ventricular systolic pressure (RVSP). The RVSP was evaluated from the maximum flow velocity from a residual VSD or tricuspid regurgitation, using the simplified Bernoulli equation. RESULTS: The LV systolic function parameters from patients versus (vs) normals showed a significantly different shortening fraction (34 +/- 5 vs 39 +/- 4; p = 0.005) and PET/ET ratio (0.34 +/- 0.04 vs 0.31 +/- 0.03; p = 0.02). None of the other studied parameters was significantly different from normal. Five (17%) patients had a small residual VSD. Two (7%) patients had mild aortic regurgitation. Tricuspid regurgitation was detected in 23 (79%) patients being trivial in 20 and mild to moderate in 3. The RVSP was quantified in 22 (76%) patients, ranging from 30 to 45 mmHg (mean +/- SD = 36 +/- 4). None of the remaining 7 patients showed changes in the end-systolic interventricular septal configuration. CONCLUSIONS: Our study shows that surgical closure of perimembranous VSD performed during the first year of life was possible without significant mobility. Furthermore, the echo allowed a complete and noninvasive cardiac evaluation of the anatomic, functional and hemodynamic status of this group of patients, thus limiting the need for postoperative control cardiac catheterization. PMID- 1632991 TI - [Echocardiographic study of 53 patients with rheumatoid mitral stenosis]. AB - In 53 patients with rheumatic mitral stenosis we performed echocardiographic study in order to define anatomic and functional alterations. We used 3.5 MHZ probe and obtained images from apical and parasternal windows. Determinations were performed by standards of the American Society of Echocardiography. Thirteen patients were men and forty women. Men's mean age was 43.5 years and women's mean age 40 years. In the men anatomic mitral valve area was 1.1 cm2 and in the women 1.3 cm2. Correlation anatomic to functional valve area was strong (r = 0.9). Mitral diastolic gradient had correlation with cardiac output, mitral valve area and ejection fraction. Pulmonary artery pressure had strong correlation with valve area and cardiac output. In conclusion, our study showed the usefulness of functional valve area in the graduation of mitral stenosis, the dependence of the mitral diastolic gradient of several cardiac events, the independence of the left atrium dimensions and also the strong dependence of pulmonary artery pressure of cardiac output and valve area. PMID- 1632992 TI - [Dyslipidemia as coronary risk factor]. PMID- 1632993 TI - [Annuloaortic ectasia: report of a case]. AB - The authors describe a case of a patient with annuloaortic ectasia (AAE) and severe aortic regurgitation. The diagnostic was made by angiography. He was submitted to a Bentall's procedure; replacement of the ascending aorta by a conduit and of aortic valve by a mechanical prosthesis with reimplantation of coronary arteries into the conduit. The only complication was atrial fibrillation with fast ventricular response. Nowadays he is clinically well, in NYHA class I. The authors make some considerations about AAE, its surgical treatment and its results. PMID- 1632994 TI - [Oxygen free radicals in cardiology]. PMID- 1632995 TI - [Classification of anti-arrhythmia drugs and their mechanism of action. Iatrogeny of anti-arrhythmia agents]. PMID- 1632996 TI - [Choice of anti-arrhythmia agents: the arrhythmia-patient binomial]. PMID- 1632997 TI - [Anti-arrhythmia agents and sudden death]. PMID- 1632998 TI - Promoting prevention services in primary care: a controlled trial. AB - We used a two-group hybrid, multiple baseline and reversal design to assess the efficacy of a prompt--an in-chart checklist--for increasing screening, counseling, and referral for 11 risk behaviors. Chart reviews for randomly selected patients of each provider showed very low baseline levels of these services for routine visits (0.2% to 3.8%). But significant increases occurred in discussion and prescription of change (although not in referrals) during intervention. Patient visits for routine gynecologic care and birth control showed higher baseline levels (10.8% to 21.0%) and also had a significant increase in discussion of risk behaviors. However, no significant change occurred in prescription or referral for these patients. Follow-up interviews of providers supported the reliability of the results and raised issues about attitudes toward primary care health promotion. Provider variability in response to the intervention suggests that more tailored interventions might increase provision of comprehensive health promotion services by a broad spectrum of primary care providers. PMID- 1632999 TI - The patient's view of hypertension and compliance. AB - Noncompliance has been identified as the predominant reason for failure of hypertension therapy. Patients may perceive hypertension as a symptomatic condition, and this view may affect compliance. In a cross-sectional study of outpatients attending a hypertension clinic, we assessed 125 veterans' understanding of hypertension, hypertension history, comorbidities, and pharmacy refills for hypertension medications. Though over 70% viewed hypertension as a symptomatic condition, symptoms were not significantly associated with pharmacy compliance. In univariate analyses, variables significantly associated with better pharmacy compliance were perceived lifetime treatment of hypertension, greater than 5-year history of medication use, perceived cause of hypertension other than diet, use of more than one hypertension drug, lack of reported departure from the prescribed medication regimen, absence of drug abuse history, and race (Caucasian). In multivariate analyses, the best predictive model of pharmacy compliance included three variables: drug abuse history, perceived cause of hypertension, and pattern of medication use. This type of information should be included in the assessment of medication compliance among hypertensive patients. PMID- 1633000 TI - Physician assessment of patient motivation: influence on disposition for follow up care. AB - This study of 3,318 outpatient visits evaluated the influence of the physician assessed level of patient motivation on the level of physician involvement in follow-up care. Data collected included patient demographics, health risk factors, physician-assessed level of patient motivation, and the disposition for follow-up care (return office visit or self-care). Physicians more frequently scheduled patients for a return office visit, regardless of assessed level of patient motivation, when they presented with a traditional biomedical problem. Patients with health promotion-disease prevention problems were more frequently relegated to self-care; patients physicians judged to be poorly motivated were four times as likely to be relegated to self-care. We discuss the implications of physician overuse of self-care strategies on the health status of poorly motivated patients. Factors influencing such physician behavior may include prior unrewarding experiences with poorly motivated patients, perceived lack of skill in affecting behavior change, time constraints, lack of reimbursement for preventive care services, and the actual process of physician education and professional socialization. PMID- 1633001 TI - Risk factors and recommendations for 230 adult primary care patients, based on U.S. Preventive Services Task Force guidelines. AB - We used a computer program based on the U.S. Preventive Services Task Force guidelines to identify recommendations for 230 adult patients who presented to an ambulatory family practice residency clinic. We entered risk factors into the computer program from sex-specific questionnaires that patients completed. On average, patients had 15.4 risk factors and 24.5 recommendations for preventive services (13.0 recommendations for screening, 10.5 for counseling, and 1.1 for immunizations). We noted a significant increase in the number of risk factors and recommendations with increasing age, except for counseling recommendations. The average patient incurs a large number of recommendations, which depend on many different risk factors, making the task of complete clinician compliance with the U.S. Preventive Services Task Force guidelines difficult. Many of these recommendations include counseling, which may take more time and require skills that clinicians may think they lack. Complete adherence may require several visits for the physician to address all recommendations. Measures to increase patient responsibility for health maintenance and innovations using comprehensive, interactive, and educational computer programs may help solve these problems. PMID- 1633002 TI - Weight reduction diets and health promotion. AB - Obesity is an important health problem. Despite record rates of dieting and the availability of numerous programs, the problem is not abating. This article discusses the popularity of fad diets, the safety and effectiveness of commonly used approaches to weight loss, and the health effects of weight change. We propose an approach in which the search for a best treatment is secondary to the development of criteria to match patients to different treatments. This approach provides an opportunity for the health professional to take advantage of the multiple weight reduction resources in the community. PMID- 1633003 TI - Attendance patterns and characteristics of participants in public cholesterol screening. AB - We conducted free, voluntary, public cholesterol screenings in supermarkets in the Rochester, New York, area during a four-month period for demonstration and research purposes. We assessed demographic characteristics and attendance patterns of the 8,583 participants. Compared with 1980 census data for the same census tracts, our participants were likelier to be white, older, female, and better educated than the general population in the area. Most screenees knew about the screenings in advance, and 79% came to the store just for screening. Weekend and weeknight screenings attracted more men and more younger people, in comparison to weekday screenings. However, referral rates based on high cholesterol (HC) test results were similar during all screening times. Overall, 22% of screenees reported a previous diagnosis of HC, but in the highest cholesterol-level group, 45% of screenees reported a history of HC. Previous awareness of HC did not vary according to screening time. These findings indicate that, like other screenings, cholesterol screenings in a public setting do not attract a representative sample of the whole population. The screenings did, however, attract a large number of high-risk individuals, many of whom had no prior awareness of HC. These results should be valuable in planning and targeting future cholesterol screenings. PMID- 1633004 TI - Application of the MRFIT smoking cessation program to a healthy, mixed-sex sample. AB - The Multiple Risk Factor Intervention Trial (MRFIT) included a smoking cessation program that was highly successful (40.3% abstinence prevalence rate at 48-month follow-up) when used with other interventions for a male, middle-aged population at high risk for coronary heart disease (CHD). Our study employed the MRFIT cessation program alone with a mixed-sex, mixed-age, healthy population. We wished to determine its effectiveness when applied in a manner similar to other smoking cessation programs. Fifty-six subjects participated in a 10-week intervention followed by maintenance or extended intervention programs. The 52% abstinence prevalence rate at the end of the 10-week intervention dropped to 32% after four months, 25% at eight months, 25% at 12 months, and 27% at 16 months. The higher cessation rates of the original MRFIT study may be related to motivation and other characteristics of the high-risk population and to the combination of the smoking component with other interventions for CHD, rather than to the characteristics of the smoking intervention itself. Although the MRFIT program is comprehensive and includes vigorous maintenance activities, it is also expensive and may not be cost-effective or as desirable as programs with slightly lower cessation rates. PMID- 1633005 TI - Evaluation of the impact of dissemination of smoking cessation methods on the low birthweight rate and on health care costs: achieving year 2000 objectives for the nation. AB - Nationwide dissemination of efficacious and cost-effective smoking cessation methods during the 1990s represents an important part of the solution to reducing the low birthweight (LBW) rate and associated health care costs. A minimum of 250,000 LBW births must be prevented during the 1990s to achieve the year 2000 LBW rate objective of 5% of total births. Annually 1,500 to 6,000 LBW births might be prevented between 1991 and 2000, and cumulatively 29,000 to 44,000, by dissemination of tested smoking cessation methods. Twelve to eighteen percent of the objective might be accomplished by dissemination. LBW births attributable to smoking might be reduced from the current 20% to 26% rate to a rate of 9% to 12% if the overall maternal smoking prevalence rate is reduced to 10% as projected in the Year 2000 Objectives. Smoking-attributable health care cost savings from dissemination would range from $22 million to $59 million. PMID- 1633006 TI - Follow-up of the use of local health department clinics for preventive care among young children. AB - We followed 18,490 infants from their first visit to a county child health clinic (CHC) in Maryland through visits through their third year of age to investigate whether their continued use of the CHCs was related to their characteristics or to the services they were provided as an infant. We classified as provided services immunization, an Early and Periodic Screening, Diagnosis, and Treatment Program (EPSDT) recommended screening, and number of visits. Immunization was associated with an increased percentage of infants who returned to the CHCs at two and three years of age. Half of the children, on the other hand, never returned to the clinics if they were not immunized as infants. These findings persisted, regardless of race, Medicaid status, completion of a screening, or number of visits in the first year of life. One-fifth of infants did not receive an immunization during one or more visits to CHCs in their first year. Failure to administer an immunization to infants appears to impede subsequent use of public health clinics for well child care. PMID- 1633007 TI - Repeat mammography among women over 50 years of age. AB - Mammography decreases mortality among women 50 years of age and older. Although recent surveys show that mammography use has increased since 1983, it continues to be underused by women at risk for breast cancer. The frequency of repeat screening at recommended intervals remains an important unanswered question. This record audit study included all visits from 1986 to 1988 for active female patients, 51-64 years of age, in a family medicine practice. The practice has a disproportionately black patient population, many of whom are on public assistance, characteristics associated with lower compliance with cancer screening guidelines. I reviewed medical records for a physician's recommendation for mammography and also for a radiology report documenting receipt of the mammogram. I also abstracted from the medical record the reason for mammography, a history of breast cancer risk factors, and sociodemographic information. In addition, I noted documentation of a clinical breast examination (CBE) and CBE results. Records for 150 patients were included in the analysis. The results indicate that repeat screening mammography is not common: 3% had three mammograms during the study period; 19% had two; 33% had one; and 44% had none. Physician recommendation for first-time mammography and clinical examination occurred with low frequency. As others report, mammography use is strongly associated with physician recommendation for a mammogram. PMID- 1633008 TI - The epidemiology of school-related injuries: new perspectives. AB - Among school-aged children, unintentional injuries are the leading cause of morbidity and mortality. We began this prospective study in a sample of nine schools within the Boulder Valley School District (Colorado) during the 1988-1989 school year in an effort to explore the etiology of school-related injuries and to provide information relevant to their prevention. During the study period, 509 injuries were reported among a population of 5,518 students, yielding an incidence of 9.22 per 100 students. Boys were nearly one and one-half times more likely to have sustained a school-related injury than girls (risk ratio (RR) = 1.41; 95% confidence intervals [CIs] 1.18, 1.68). We found a significant difference among injury rates by school level (P less than .001). Middle/junior high students had the highest rate, followed closely by elementary students and distantly by high school students. Sports activities accounted for the largest percentage of school injuries (53%), and the percentage of sports-related injuries increased with increasing grade level. Analysis of injury rates by school location revealed that high school students were most frequently injured in the gym (1.52 per 100), middle/junior high students on the athletic field (4.26 per 100), and elementary students on the playground (6.12 per 100). Using injury location as the focal point, we examined relationships among the variables sport/activity, body site, and nature of injury. We found that a large percentage of injuries sustained on the athletic field or in the gym were similar and affected similar body sites, whereas playground injuries differed in their nature and in body site affected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1633009 TI - What's in a name? PMID- 1633010 TI - [Effect of growth hormone and parenteral nutrition on the catabolic phase following major digestive surgery]. AB - The purpose of the present study was to determine if the administration of a biosynthetic human growth hormone (bGH) was able to enhance the efficacy of total parenteral nutrition (PN). Patients (n = 38) who had undergone major gastrointestinal surgery were randomly divided in two groups. Group I (n = 20) treated only with PN and Group II (n = 18) treated as in Group I plus bGH (4 UI/daily). Our study shows that the administration of bGH produces a significant increase in serum levels of growth hormone and Somatomedin-C. It also caused a positive nitrogen balance from the first 24 hours on (p less than 0.01). In Group II on day 12 after operation a statistically significant increase in transferrin (p less than 0.05), albumin (p less than 0.01) and total proteins (p less than 0.02) was observed. Our study suggest that the administration of bGH produces, perhaps through Somatomedin-C as mediator, an increase in protein synthesis. PMID- 1633011 TI - [Role of the vagal system in changes in small intestinal motility induced by psychological stress. Experimental study on dogs]. AB - The objectives of the present study were: 1) to describe the modifications in motility of the small intestine in response to situations of psychic stress during fasting and postprandial periods. 2) To analyse the possible involvement of the vagal system in these modifications. For this we used a total of 40 dogs. The motility of the small intestine was recorded using electromyography techniques (monopolar electrodes) and manometric techniques (submucous microballons). The stress stimulus consisted in the complete body immobilization of the animal in plaster. We show that stress induced a significant increase in the intestinal motility index (percentage of show waves followed by the action potential) in the three locations of the intestine studied (duodenum, angle of Treitz and proximal part of the jejunum) during the fasting (p less than 0.001) and postprandial periods (p less than 0.001). Finally, we demonstrate that vagotomy prevents the effect of hypermotility causes by the psychic stress. We can conclude that psychic stress does indeed modify the normal motility of the small intestine, both in the fasting and postprandial periods, and the vagus is implicated in this hypermotility response. PMID- 1633012 TI - [Complications and possible risk factors in endoscopic polypectomy of the colon]. AB - We review the incidence of iatrogenic complications in a serie of 661 patients who underwent endoscopic polypectomy, performed by the same team of endoscopists and using similar technique. We discuss the role of age, sex, associated diseases, coagulation abnormalities and polyp features (size, location, shape and malignancy) in the development of complications. Five severe complications (0.75%, 3 hemorrhages and 2 perforations) were detected. Two patients required blood transfusion and two other patients surgical treatment. Recovery was successful in all patients. In eight patients (1.21%) mild complications which did not required further treatment were present. According to previously published data, these results are satisfactory. Polyp size proved to be the only risk factor with statistical significance; 23.36 +/- 14.17 mm. in complicated polypectomies vs 8.12 +/- 4.21 mm. in non-complicated cases (p less than 0.001). The remaining parameters analyzed showed no significance and therefore no predictive value. PMID- 1633013 TI - [Synchronous carcinoma of the colon and the rectum (21 cases)]. AB - We present a retrospective study on 610 patients with colorectal cancer diagnosed over a 10 year period; 21 patients (3.4%) had synchronous multiple primary carcinomas. Age and clinical symptoms were similar to those with single carcinomas. In 57% of patients, the presence of synchronous neoplasms was diagnosed preoperatively by colonoscopy and/or barium enema, in 38% peroperatively and in 5% postoperatively. The more frequent localizations were rectum-sigmoid colon (24%) and descendent colon-sigmoid colon (19%). Three patients had 3 synchronous tumors, respectively. According to the Dukes classification, 80% of the patients had stage B or C. The five-year survival rate was 61%, similar to that for colon cancer in general. We emphasize the importance of preoperative identification of synchronous lesions; the whole colon should be investigated before surgery in order to ensure that no synchronous tumor has been missed or to change planned surgery. PMID- 1633014 TI - [Cholelithiasis in the region of Cartagena: an approximation to its real incidence based on the study of its symptomatic group]. AB - We have studied the frequency of cholelithiasis in a group of patients who complained of clinical symptoms of cholelithiasis and lived in the region of Cartagena. This group of patients accounts for 40% of all the patients suffering from cholelithiasis this would account for 0.5% of the whole population and 1% of the exposed population over 30 year-of-age. Our results suggest that the population living in the region of Cartagena has a low-risk for cholelithiasis. PMID- 1633015 TI - [Cholelithiasis and cancer: a study using precursor changes in a population with low incidence of cholelithiasis]. AB - In order to assess the role of cholelithiasis in the pathogenesis of gallbladder carcinoma in a low-risk population for cholelithiasis and gallbladder cancer, we have studied the relationship between cholelithiasis and cancer. Our findings suggest that, both the relationship between cancer and cholelithiasis, and the frequency of precursors lesions, are very similar to those obtained in surveys carried out in high-risk populations for both conditions. Our findings bear out our hypothesis that cholelithiasis plays a main role in the pathogenesis of gallbladder carcinoma. PMID- 1633016 TI - [Biliary ileus: enterolithotomy only or radical surgery?]. AB - Eleven patients, 8 women and 3 men, mean age 69.9 years (range 54-81) were operated with a gallstone ileus during a seven years period. Echography and barium study of small bowel were made in 8 and 2 patients, and gave a diagnostic rate of 37% and 100%, respectively. A preoperative diagnosis was made in 72.2% of cases, simple enterolithotomy was made in 8 cases and in three cases a definitive treatment of biliary pathology was added. There was no mortality and a major complication was observed in 1 patient without biliary surgery (evisceration and recurrence of biliary ileus); no major complications were seen in patients with primary biliary surgery. With a careful, selection, surgery can be made without mortality nor morbidity. PMID- 1633017 TI - [Wilson's disease]. PMID- 1633018 TI - [Phlegmonous gastritis. Report of a case induced by Pseudomonas aeruginosa]. AB - The authors present a case of phlegmonous gastritis in a 65 year old patient. The diagnosis was made in the operating room and the treatment was conservative; no gastric resection was done. This clinical entity is interesting because it is a least frequent pathology, the pathogenic bacteria which was the cause (Pseudomona aeruginosa) has at this time not been reported in the literature, including the favorable outcome of the patient without gastric resection. PMID- 1633019 TI - [Digestive hemorrhage caused by vascular malformation (Rendu-Osler-Weber). A diagnostic and therapeutic challenge]. AB - We present a case of gastrointestinal bleeding due to vascular malformation (Osler-Weber-Rendu disease), without cutaneous manifestations but with mucous manifestations and familiar and personal history of epistaxis. Until diagnosis, the patient underwent multiple radiologic and endoscopic tests and two surgical procedures. We would underline the diagnostic and therapeutic difficulty of recurrent gastrointestinal bleeding secondary to vascular malformation. PMID- 1633020 TI - [Cystic lymphangioma of the colon: endoscopic treatment and diagnosis]. AB - We present a case of cavernomatous cystic lymphangioma in the hepatic angle of the colon, a extremely rare benign tumor developed in a patient under continued radiologic and endoscopic surveillance because of multiple polyps and colon carcinoma. The lesion was asymptomatic and was diagnosed in a routine follow-up colonoscopy. The endoscopic appearance was similar to that of an adenomatous polyp and was safely resected by polypectomy without evidence of relapse to the present time. Trends in the treatment of lymphangioma have been changing since the development of snare polypectomy; thus before 1980 it was treated mainly by surgery, while at present lymphangiomas less than 2 cm have been removed more frequently by polypectomy. PMID- 1633021 TI - [Endoscopic retrograde cholangiopancreatography in Mirizzi's syndrome]. AB - Mirizzi's syndrome is characterized by compression and or stenosis of the common duct as a consequence of impaction of a stone in the gallbladder neck, the cystic duct and eventually by a cholecystobiliary fistula. Preoperative diagnosis is important to avoid iatrogenic injury of the biliary tree. We present two cases with Mirizzi's syndrome confirmed at operation in whom ERCP was done prior to the operation. In one of them the examination was diagnostic, while in the other, cystic duct compression and absence of the gallbladder image were the non specific findings. PMID- 1633022 TI - [Peritoneal mesothelioma]. PMID- 1633023 TI - [Stercorous perforation of the colon]. PMID- 1633024 TI - [Intestinal inflammatory disease or Behcet's disease]. PMID- 1633026 TI - [John Arderne (c. 1307-1390). Father of proctology]. PMID- 1633025 TI - [Hemoperitoneum following spontaneous rupture of ileal varix]. PMID- 1633027 TI - [Measurements of MEG]. PMID- 1633028 TI - [What the dipole tracing method can do at present and in future]. PMID- 1633029 TI - [Magnetoencephalography in clinical epileptology]. PMID- 1633030 TI - [Magnetoencephalography of cerebral evoked responses]. PMID- 1633031 TI - [Effect of ulinastatin on postischemic brain edema in cats]. AB - The effect of ulinastatin on postischemic brain edema was investigated in adult mongrel cats. Focal brain ischemia was produced by occlusion of the left middle cerebral artery (MCA) through the transorbital approach. Following two hours of occlusion, the brain was reperfused for two hours. In all seven animals of the ulinastatin-treated group, ulinastatin was administered intravenously at a dose of 50000 U/kg before and after occlusion. In the control group, six animals were given only vehicle. Measurements of regional cerebral blood flow (rCBF) were performed before MCA occlusion by the hydrogen clearance method, and then repeated every 30 minutes during and after occlusion. Following two-hour reperfusion, the animals were sacrificed by intravenous KCl injection. Specific gravity of the cortex, where rCBF was measured, was determined by microgravimetric method. In the analysis of specific gravity of the cortex, in which mean rCBF during ischemia was above 15ml/100g/min, no significant difference was found between the ulinastatin-treated and control groups. In the specimen with mean rCBF below 15ml/100g/min during ischemia, cortical specific gravity was reduced remarkably in the control group, while not decreased in the ulinastatin-treated group. The difference was statistically significant between two groups (p less than 0.001). These findings suggest antiedema effect of ulinastatin. PMID- 1633032 TI - [Effects of stimulation of the vertebral nerve around the proximal vertebral artery on pupil and the autonomic nervous system--a contribution to pathophysiology of Powers' intermittent vertebral artery compression syndrome]. AB - In order to elucidate the pathophysiology involved in Powers' intermittent vertebral artery compression syndrome, the author investigated sympathetic and parasympathetic changes produced by stimulation of nerves around the proximal vertebral artery (the vertebral nerve) in anesthetized and immobilized cats. These changes were observed mainly through pupillary changes, pulse and blood pressure, evoked potentials in the lateral horn of the upper thoracic cord (centrum ciliospinale), in the cervical sympathetic trunk, and in the short ciliary nerve. Electrical stimulation of vertebral nerve and local application of K ion around the vertebral artery produced stimulus-dependent ipsilateral mydriasis; when stimulation of higher strength was applied pronounced ipsilateral and mild contralateral mydriasis and hypertension occurred. Electrical stimulation of perivascular tissue around the subclavian artery proximal to origin of the vertebral artery showed ipsilateral mydriasis; while on stimulating the distal subclavian, the costcervical, the omocervical and the internal thoracic arteries did not show any pupillary response. Neuronal discharges in the lateral horn of upper thoracic cord and in the cervical sympathetic trunk showed stimulus-dependent increases on stimulating the vertebral nerve; while, inhibitory responses were observed in the short ciliary nerve formed by parasympathetic nerve fibers. From the data available, it seems likely that the stimulation of periarterial neural structure of the vertebral artery produced sympathetic excitatory as well as parasympathetic inhibitory neuronal discharges simultaneously may probably be derived from the integrating autonomic center in the hypothalamus. PMID- 1633033 TI - [A case of motor neuron disease with IgM gammopathy which showed anti-cerebrum antibody]. AB - A patient, 50-year-old female, developed progressive weakness of lower extremities, and gait disturbance for 2 years. Neurological examination revealed hyperreflexia with pathological reflex, fasciculation in the limbs and tongue, muscle weakness and atrophy in distal limbs, but no sensory disturbance. Needle EMG showed neurogenic findings compatible with motor neuron disease (MND). Laboratory data showed polyclonal IgM hyperimmunoglobulinemia, positive several autoimmune antibodies including antisingle strand DNA antibody (Ab), ENAab, SS-A ab and RA. There were no antibodies for gangliosides and Myelin-associated glycoprotein (MAG), but positive antibody for 54KD protein of cerebral gray and white matter. The clinical manifestations including gait disturbance and muscle weakness, and serum IgM level were moderately improved by plasmapheresis which is considered important for consideration of causes of MND. PMID- 1633034 TI - [Agenesis of the internal carotid artery--report of a case combined with arachnoid cyst in a child]. AB - A case of agenesis of the internal carotid artery combined with arachnoid cyst is reported. This 11-year-old boy had occasionally complained headache and nausea since he was of 9 years old. He was admitted to our hospital because of an epileptic seizure. Physical and neurological examinations on admission were normal. A CT scan showed a cystic mass in retrocerebellar region. MRI suggested absence of flow void area indicating internal carotid artery in the cavernous sinus on left side. Left common carotid angiogram showed absence of the internal carotid artery. Bilateral A2 segments were supplied by right A1 with tortuous anterior communicating artery. Left middle cerebral artery and left ophthalmic artery were supplied via dilated left posterior communicating artery on left vertebral angiogram. Thin slice, axial target image of the CT revealed absence of the left bony carotid canal. MRI by 3D TOF method confirmed no blood flow in this area. MR angiography provided sufficient information about cervical vessels non invasively. 123I-IMP SPECT image ascertained no hypoperfusion area in left cerebral hemisphere. Convulsion was controlled with sodium valproate. Association of agenesis of the internal carotid artery and arachnoid cyst could be a coincidence. PMID- 1633035 TI - [A case of acute subdural hematoma in the posterior fossa with idiopathic thrombocytopenic purpura]. AB - Intracranial bleeding is one of fatal complications in idiopathic thrombocytopenic purpura although its reported incidence is low. A case of spontaneous acute subdural hematoma complicated with idiopathic thrombocytopenic purpura was reported. He was hospitalized complaining of sudden onset of headache and nasal bleeding without neurological deficit. CT scan revealed subdural hematoma in the posterior fossa especially below the tentorium cerebelli. Further hematological examination proved very low platelet count (1,000/mm3) and antiplatelet antibody in confirmation of a diagnosis of idiopathic thrombocytopenic purpura. As his neurological status was good, he was treated medically. His symptoms and platelet count improved gradually with corticosteroid therapy. Reviewing the literature, acute subdural hematoma with idiopathic thrombocytopenic purpura was quite rare and only three cases reported. PMID- 1633036 TI - [Oculomotor nerve palsy due to small midbrain infarct--functional topography based on MRI findings]. AB - This is a report of 3 cases presented with oculomotor nerve palsy caused by small midbrain infarct. The aim of this report is to clarify the functional topography of intranuclear and intrafascicular portion of the oculomotor nerve with MRI. Three cases are 2 males and 1 female, ranging 51 to 68 years in age. Except for the long tract signs at the acute stage, cardinal sings were all eye-related, incomplete in 1 case and pupil sparing-type in 2 cases. In MRI, the size of the lesion extended 5 to 12 mm. In the incomplete palsy case, the infarction extended from the level immediately below the 3rd ventricle into the whole length of midbrain, whereas in the pupil-sparing types, more limited lesion excluding the upper part of the midbrain was noted. Anatomically the longitudinal size of the nucleus is 10mm and nerves functionally related to pupil reaction, eye motion and eyelid elevation are arranged in rosrocaudal order. Therefore, it is speculated that in midbrain, intrafascicular location of nerve fibers associated with pupil reaction is rostral and oculomotor nerve palsy of pupil sparing type is caused by the lesion excluding the rostral midbrain. MRI findings of the present 3 cases are compatible with this speculation. The lowest border of red nucleus is at the level of superior colliculus, whereas oculomotor nucleus has its lowest margin at the inferior colliculus. Therefore, red nucleus becomes an informative landmark to visualized the level of oculomotor nerve injury, since the red nucleus is clearly demonstrated in high intensity in T2 weighted image. PMID- 1633037 TI - Ductus arteriosus aneurysm imaging using modern diagnostic methods. AB - An aneurysm of the ductus arteriosus carries a high risk of rupture. The radiologic findings are described, based on a review of the literature, and on our experience of 5 patients, successfully diagnosed and treated. A left-sided mediastinal mass is always present, obscured only if the aneurysm has already ruptured. Although the lesion seems to be congenital, conventional radiology sometimes demonstrates wall calcifications. Ultrasonography is well suited to demonstrate the vascular nature of the mass, but interpretation may be difficult because of intervening air-containing lung parenchyma. CT, especially using dynamic scanning with contrast enhancement, is an excellent noninvasive diagnostic method. Angiography is frequently necessary to demonstrate patency or occlusion of the aortic and pulmonary ends of the ductus. The differential diagnosis must include a large number of mediastinal tumors. A temporary widening of the ductus in the newborn is common and must be differentiated from a true aneurysm. Surgical treatment today is usually successful. PMID- 1633038 TI - Iliac artery stenting--clinical experience with the Palmaz stent, Wallstent, and Strecker stent. AB - A total of 82 iliac artery lesions (62 stenoses and 20 occlusions) were treated with 3 different types of endovascular metallic stents (12 lesions with the Palmaz stent, 36 with the Wallstent, and 34 with the Strecker stent). The complication rate was 12%. Occlusion of 2 Wallstents occurred 4 and 12 weeks after stent placement, respectively. Both stents were recanalized by local fibrinolysis. One Strecker stent occluded after 8 months. The observation period was 3 to 26 months (mean 9.7 months). The patency rate with secondary intervention (fibrinolysis) was 100% after 3 and 6 months, and 98% after 9 months. All 3 stent designs turned out to be effective in the treatment of complicated iliac artery occlusive disease. PMID- 1633039 TI - Clinical utility of real-time compression ultrasonography for diagnostic management of patients with recurrent venous thrombosis. AB - In the diagnostic management of patients with clinically suspected recurrent deep vein thrombosis (DVT), there are potential limitations to all available diagnostic techniques. Since venous abnormalities may persist for some time after an acute thrombosis, the usefulness of compression ultrasonography (US) for the detection of recurrent DVT may be jeopardized. We determined the rate of normalization of an abnormal compression US test of the popliteal and the common femoral veins in patients after a first episode of proximal DVT. In a cohort of 60 consecutive patients, the test result was normalized in only 29, 44, 54, and 60% of patients at 3, 6, 9, and 12 months, respectively. The investigation shows that for the detection of recurrent DVT of the leg, real-time compression US (using the single criterion of compression of the common femoral and popliteal vein) is of limited value. Future studies need to be performed, using more subtle interpretation of the compression US result, by quantifying the extent of residual thrombus, which may increase the usefulness of this test in patients with recurrent symptoms. PMID- 1633040 TI - Complications of percutaneous pericardiocentesis under fluoroscopic guidance. AB - Complications in 352 cases of fluoroscopy-guided percutaneous pericardiocentesis accomplished through an indwelling catheter were reviewed following surgery and non-surgery. Thirteen major complications were found, namely 3 cardiac perforations, 2 cardiac arrhythmias, 4 cases of arterial bleeding, 2 cases of pneumothorax in children, one infection, and one major vagal reaction. No significant difference in complications was found between pericardiocenteses for pericardial effusions after cardiac surgery (n = 208) and those for effusions of non-surgical (n = 144) origin. Fluoroscopy-guided pericardiocentesis by the subxiphoid approach with placement of an indwelling catheter is a safe method for achieving pericardial drainage in both surgical and non-surgical effusions. Accidental cardiac perforation with a fine needle is a minor complication as long as the needle is directed towards the anterior diaphragmatic border of the right ventricle and drainage is achieved with a reliable indwelling catheter. PMID- 1633041 TI - Influence of CT on tumor classification of laryngeal carcinomas. AB - The routine use of CT in 51 consecutive patients with squamous cell carcinoma of the larynx revealed cartilage involvement or extralaryngeal tumor growth consistent with a T4 tumor which made 14 patients candidates for laryngectomy. Only 5 of these had a T4 classification by clinical examination while 8 cases were upstaged from T3. Except for one supraglottic tumor upstaged from T2 to T4, CT did not change the classification for T1 and T2 tumors, whose localization was mainly glottic, and there were 2 false-negative examinations. It is concluded that CT is mandatory only in advanced tumors of the glottic region or when the anterior commissure is involved. However, in suspected malignancies of the sub- or supraglottic regions CT should always be carried out because these patients are at an increased risk of unexpected deep tumor growth. PMID- 1633042 TI - Gd-DTPA-enhanced MR imaging of pituitary macroadenomas. AB - In a study comprising 40 patients with pituitary macroadenomas, MR imaging was performed before and after administration of Gd-DTPA. Before contrast administration T1- and T2-weighted images were obtained, and after the injection, frontal and/or sagittal T1-weighted images. Tumour extension and delineation, relationship to adjacent structures, and signal intensity patterns were evaluated. Compared with pre-contrast T1-weighted images only, post-contrast images provided considerable additional information, but not infrequently this information could also be extracted from pre-contrast T2-weighted images. Post contrast images were superior regarding the tumour relationship to the cavernous sinus and to the normal pituitary tissue. T2-weighted images were helpful in the diagnosis of degenerative changes, in particular intratumoural haemorrhage. A positive correlation was found between the T2 value (from dual echo sequences) and the degree of enhancement in areas with an appearance of solid tumour tissue, and the enhancement was significantly lower in GH-secreting tumours than in non secreting ones. It is concluded that the use of Gd-DTPA is often justified in pituitary macroadenomas, particularly in pre-operative evaluation. PMID- 1633043 TI - CT showing early ventricular dilatation after subarachnoidal hemorrhage. AB - We performed a retrospective analysis of 398 patients with subarachnoidal hemorrhage (SAH) confirmed by CT. On the first CT examination the temporal horns were enlarged in 84%, the frontal horns in 32%, and the third ventricle in 21% of the patients. The amount of blood in the basal cisterns was highly correlated to dilatation of the temporal horns. The temporal horns were enlarged even when small amounts of blood were found in the cisterns. The frontal and temporal horns were dilated only when moderate or large amounts of blood were present in the cisterns. In 24 patients no blood was seen in the basal cisterns on CT performed within 5 days of the hemorrhage; none of the 3 patients with aneurysms showed normal temporal horns while 18 without demonstrable aneurysms had normal, and 3 had moderately dilated, temporal horns. Because the temporal horns cannot usually be seen at CT of healthy individuals, dilatation could be a useful sign in the diagnosis of SAH. PMID- 1633044 TI - MR imaging of spinal lymphoma. AB - Fourteen patients with spinal lymphoma examined by MR imaging were reviewed. Thirteen of them also had extraspinal lymphoma. Vertebral involvement was found in 12 patients, epidural in 10, and paraspinal in 8 patients. On the basis of MR imaging at 0.3 T, spinal lymphoma may be divided into three types of growth pattern according to the main location: paraspinal, vertebral, and epidural. Most frequently, all three locations were found simultaneously on MR (7/14). In one patient the location was vertebral with epidural extension, in one paraspinal with vertebral extension, in 3 it was entirely vertebral, and in 2 entirely epidural. Multiple plane T1-weighted imaging gave complete information about the extent of spinal lymphoma. The signal intensity was lower than or equal to muscle and lower than bone marrow in paraspinal and vertebral lesions on T1-weighted images and high on T2-weighted images. Epidural lesions showed a hypo- or isointense signal relative to the cord on T1-weighted images except in one case and a hyperintense signal on T2-weighted images. Compression of the cord and cauda equina due to bulging of diseased vertebral bodies and epidural lesions was well demonstrated. MR imaging was also found useful in the follow-up of treatment. PMID- 1633046 TI - Assessment of liver iron overload in thalassemic patients by MR imaging. AB - The use of MR imaging has been proposed for the assessment of the hepatic iron overload in transfusion-dependent thalassemic patients treated with desferrioxamine. The aim of the study was to correlate serum ferritin levels and MR signal intensity of the liver parenchyma. Results on 12 patients showed that the ratios between the signal intensity of liver parenchyma and muscle and fat are promising parameters for predicting iron overload. PMID- 1633045 TI - Abdominal ultrasonography in myelofibrosis. AB - The findings at abdominal ultrasonography (US) in 40 patients with myelofibrosis were reviewed, 20 patients being examined at initial diagnosis and 31 at later stages. Splenomegaly was found in 80% at initial diagnosis and in 97% at later stages. The spleen of 2 patients appeared homogeneously hypoechoic and inhomogeneous in one. Focal splenic lesions were seen in 5, and calcifications in 6. Mixed splenic lesions proved to be metastases in one and hyperechoic lesions in another patient were due to extramedullary hematopoiesis. Hepatomegaly was found in 25% at primary diagnosis and in 39% at later stages. Focal hepatic lesions were seen in 7 patients, and proved to be metastases in 3. The focal lesions in 2 of these patients were extramedullary hematopoiesis, which was hypoechoic in one and hyperechoic in the other. Ascites was seen in 4 patients and lymphadenopathy in one. US could not reliably differentiate between extramedullary hematopoiesis and malignancy. Fine-needle biopsy may be performed for definitive diagnosis. PMID- 1633047 TI - Experimental transjugular portacaval shunt. Use of a fine-needle puncture device for the implantation of Strecker stents. AB - A transjugular portacaval intrahepatic stented shunt was created in 16 pigs without induced portal hypertension. A fine needle (OD 0.7 mm) was used for the transjugular puncture of the portal vein. The puncture was done directly from the inferior vena cava in 5 cases and from the right liver vein in 11 cases. The puncture tract was dilated and subsequently supported by a Strecker stent. The stented shunt was patent in all cases immediately after the stent placement, but was obstructed by fibrous tissue in 7 of 8 cases reexamined by angiography and autopsy after 4 weeks. Complications seem to be related to the choice of the puncture site, with fewer complications when the puncture was done via the right hepatic vein. PMID- 1633048 TI - Air enema revisited in assessment of colitis. AB - Plain radiographs and air enema were performed in 37 patients with ulcerative colitis, 7 patients with proctitis, and 8 patients with Crohn's disease. The air enema was superior to plain radiographs for diagnosing colitis, and for delineating the extent of disease and the degree of mucosal involvement. The air enema is simple to perform and easy to evaluate as shown by an almost complete agreement between 2 observers. PMID- 1633049 TI - CT demonstration of fat density in renal cell carcinoma. AB - The presence of fat in a renal mass is almost pathognomonic of angiomyolipoma. We report a rare instance of CT demonstration of foci of fat density in a renal cell carcinoma. PMID- 1633050 TI - Iopentol in urography. A clinical comparison between iopentol and metrizoate including delayed reactions. AB - A double-blind comparative study of the nonionic contrast medium iopentol and the ionic contrast medium metrizoate for urography was carried out in 200 adult outpatients. Significantly less discomfort and other side effects were observed following iopentol than following metrizoate. No serious adverse reactions and no clinically significant alterations in heart rate or blood pressure were observed. A questionnaire was used to record delayed symptoms, from 30 min after contrast medium injection and for one week. The response rate was 92% and delayed adverse events were reported by 45%. The incidence of delayed reactions was significantly lower following iopentol than following metrizoate, i.e., delayed arm pain, fatigue, headache, diarrhea, nasal congestion, and rash. Delayed arm pain was probably due to contrast medium induced thrombosis in 1% following iopentol and in 8% following metrizoate. Most other symptoms were probably related to a combination of nocebo effect and coincidentally occurring symptoms. The urograms with both media were of similar high quality. Iopentol was found a suitable contrast medium for urography. PMID- 1633052 TI - Monte Carlo simulation of multiple scattering in Compton spectroscopy. AB - The Compton scattered photons from a scattering medium can be analyzed in a Compton spectrometer and the primary energy spectrum derived using the Compton equation. Since the reconstruction algorithm assumes that only singly-scattered photons from the scatterer are detected, multiply-scattered photons introduce errors into the measurements unless they can be accurately corrected for. In this work, a Monte Carlo collision density estimator was used to determine the contribution from photons multiply-scattered from a Lucite scatterer in the form of a square rod. The ratio of multiply- to singly-scattered photons was determined for rod thicknesses from 0.5 to 5 mm and photons of energy 20 to 110 keV. The ratio in percent can be well approximated as a linear function of energy with slope 2.2. For thicknesses below 2 mm, the ratio is less than 5% at all energies. PMID- 1633051 TI - Granulocyte adherence is inhibited by radiographic contrast media in vitro. AB - Different amounts of diatrizoate, ioxaglate, iohexol, iodixanol, NaCl 1,000 mOsm/kg, mannitol 1,098 mOsm/kg, and meglumine (meglumine concentrations corresponding to the content in the diatrizoate solutions) were added to either whole blood or a suspension of granulocytes in autologous plasma, and the adherence to nylon fibers was determined. At high concentrations all the investigated contrast media (CM) inhibited granulocyte adherence. The degree of inhibition was significantly greater when the ionic CM diatrizoate and ioxaglate were used, as compared with the nonionic media. Meglumine solutions at high concentrations also inhibited adherence but significantly less than diatrizoate solutions containing the same amount of meglumine. Diatrizoate showed the greatest inhibitory effect on granulocyte adherence, and significant inhibition could be detected even with a 1.25% solution. PMID- 1633054 TI - Work redesign: ensuring success. PMID- 1633053 TI - Collaboration: the future of health care. PMID- 1633055 TI - Of quorums and quality: integrating shared governance and continuous quality improvement. PMID- 1633056 TI - Power spectral EEG analysis and EEG variability in obsessive-compulsive disorder. AB - Spectral EEG characteristics of thirteen patients with severe Obsessive Compulsive Disorder (OCD) were investigated topographically. The finding of predominantly left posterior frontal to mid-temporal theta-2 is discussed in light of previous EEG studies and recent neuroradiologic findings. PMID- 1633057 TI - Dipole tracing in childhood epilepsy with special reference to rolandic epilepsy. AB - To assess the clinical applicability of dipole tracing in childhood epilepsy, the location and stability of electric source generator of focal spikes seen in EEG of epileptic children were investigated using this method. The patients were divided into 3 groups; benign childhood epilepsy with centrotemporal spikes (BCECS, Group A, n = 14), other types of epilepsy with centrotemporal spikes (Group B, n = 15) and epilepsy with focal spikes in other areas (Group C, n = 13). The spike dipole in each group was analyzed using dipole tracing method. The following results were obtained. (1) The spikes of BCECS were characterized by constantly stable dipoles, compared to those of the other types of childhood epilepsy. The spikes of epileptic children with mental retardation mostly lacked the stability of dipoles. These seemed to suggest that the stability of dipoles was closely related to the prognosis and pathophysiology of epilepsy. (2) The dipoles of BCECS were localized strictly in the Rolandic area. Dipole tracing from EEG spikes was considered to contribute to the elucidation of the pathophysiology of childhood epilepsy. PMID- 1633058 TI - Topographic distribution of the periodic discharges in Creutzfeldt-Jakob disease (CJD). AB - A characteristic EEG abnormality in patients with Creutzfeldt-Jakob disease (CJD) consists of periodic high voltage bilateral diphasic or triphasic sharp waves widely distributed over both hemispheres. The mechanism underlying these electrographic manifestations is, however, unclear. To increase our understanding of these phenomena, we have employed the technique of microcomputer brain mapping, to analyze the electrical fields of the bilaterally-distributed complexes in four patients with CJD. Ten generalized discharges were studied in each patient. The EEG analysis demonstrated variability in the area of onset as well as the field maxima between the different complexes among patients as well as between discharges in each patient. The generalized pattern seen in routine EEG was clearly shown on brain mapping to be not strictly generalized from onset, nor bilaterally symmetrical. These findings may suggest multifocal areas of onset of the generalized discharges, or alternating pathways of activation of the cortical areas by a subcortical pacemaker. PMID- 1633059 TI - Equivalent EEG sources determined by FFT approximation in healthy subjects, schizophrenic and depressive patients. AB - In recent years, as a result of increasing calculation power of computers and with the aid of appropriate computer programs it has been made possible to calculate equivalent dipoles as intracranial representations of cerebral electrical activity. The present study investigated the localization of intracerebral equivalent dipoles in healthy controls and psychiatric patients. The equivalent dipole sources were calculated for conventional frequency bands of the background EEG. This was performed using the FFT approximation by Lehmann and Michel. Results showed more anterior equivalent sources for alpha and beta activity in all patients compared to controls. The beta activity was also generated in deeper brain structures in controls compared to patients. These results indicate that frequency bands may be generated in different brain structures in patients suffering from psychiatric diseases as compared to healthy controls and that the calculation of equivalent dipole sources may be a way to perform a sensible and substantial data reduction. PMID- 1633060 TI - Topographic analysis of visual evoked potentials from flash and pattern reversal stimuli: evidence for "travelling waves". AB - In this mapping study of the entire scalp area, the responses to flash (FL) and pattern reversal (PR) stimuli were studied in 34 normal subjects. The N70, P100, N135 and P180 were similar from both stimuli but with some differences in amplitude and latency, especially the variability of the latency of P100 from FL. A polarity inversion was usually seen for all components, especially at opposite ends of the scalp and a zero-potential was noted for all four components near Cz Pz. Evidence is seen that the frontal N100 is likely not the other end of a dipole involving the posterior P100. Lateral components as P120, N150 and N200 were also described. The major finding was evidence of "travelling" waves that appear to move in both the AP and PA directions throughout the scalp that eventually arrive on the posterior regions and appear as N70, P100, N135 and P180. PMID- 1633061 TI - The EEG mapping in the evaluation of patients with late onset epilepsy. AB - In 62 patients with late onset epilepsy the findings of EEG mapping routine EEG and CT were compared. Forty four patients had generalized, 18 partial seizures. In 39 patients (63%) EEG mapping revealed focal changes but only in 24 patients (39%) using routine EEG alone. Thus the EEG mapping showed focal abnormalities significantly more often and this could be demonstrated in the separated groups of patients with generalized or partial seizures as well. Lesions in CT occurred in 39 patients (63%). The focal abnormalities in EEG mapping were significantly related to the lesions in CT. Moreover focal changes corresponding to CT lesions were obtained by means of EEG mapping in 32 patients (82%) but only in 20 patients (51%) using routine EEG and in that way the EEG mapping could indicate focal lesions in CT significantly more often than routine EEG. Regarding etiology this was especially seen in the group with vascular origin of epilepsy. PMID- 1633062 TI - Antimalarial pharmacokinetics and treatment regimens. PMID- 1633064 TI - Captopril augments both basal and frusemide-induced natriuresis in normal man by suppression of circulating angiotensin II. AB - 1. We studied the renal effects of reinfusing low dose angiotensin II (1 ng kg-1 min-1) into seven salt-replete healthy volunteers after pretreatment with the angiotensin converting enzyme (ACE) inhibitor captopril (25 mg) to establish whether the natriuretic and renal haemodynamic responses to ACE inhibition in normal man result from suppression of circulating angiotensin II. In the same subjects we also studied the effect of captopril (25 mg) with and without exogenous angiotensin II (1 ng kg-1 min-1) on the natriuretic response to intravenous frusemide (20 mg). 2. In the pre-frusemide study captopril increased absolute and fractional excretion of sodium and paraaminohippurate clearance but had no effect on inulin clearance. 3. Reinfusion of angiotensin II after captopril pretreatment completely suppressed the renal effects of ACE inhibition, yielding renal vasoconstrictor and antinatriuretic effects equivalent to those produced by infused angiotensin II in the absence of captopril. 4. Frusemide increased renal sodium excretion without affecting paraaminohippurate or inulin clearance. Captopril augmented frusemide-induced natriuresis and again this effect was reversed by angiotensin II reinfusion. 5. We conclude that captopril augments both basal and frusemide-induced renal sodium excretion in normal man. Our findings suggest that these renal responses to ACE inhibition may be mediated by inhibition of circulating angiotensin II, specifically its renal tubular salt retaining actions, rather than via effects on other neurohumoral systems. PMID- 1633063 TI - Medical management of hypercalcaemia. AB - 1. Hypercalcaemia is a common disorder, which frequently requires specific treatment either to control symptoms, or to prevent the development of irreversible organ damage or death. Although the best and most effective way of controlling hypercalcaemia in the long-term is to treat the underlying cause, medical antihypercalcaemic therapy is often required in clinical practice, either as a holding measure, or because the primary disease cannot itself be treated. 2. The mainstays of medical antihypercalcaemic therapy are firstly, to promote calcium excretion by the kidney by restoring extracellular volume with intravenous saline and secondly, to administer pharmacological agents which inhibit bone resorption. Measures which seek to reduce intestinal calcium absorption are seldom effective. 3. Intravenous bisphosphonates are the treatment of first choice for the initial management of hypercalcaemia, followed by continued oral, or repeated intravenous bisphosphonates to prevent relapse. These drugs have a relatively slow onset of action (1-3 days) but have potent and sustained inhibitory effects on bone resorption, resulting in a long duration of action (12-30 days). 4. Of the other agents available, calcitonin has an important place in the management of severe hypercalcaemia where a rapid effect is desirable; calcitonin is best used in conjunction with a bisphosphonate however, because of its short duration of action. Intravenous phosphate also has a place in the emergency management of severe hypercalcaemia, but is probably best reserved for patients in whom other less toxic therapies have failed. Corticosteroids are generally ineffective except in certain specific instances and are best avoided in the routine treatment of undiagnosed hypercalcaemia. PMID- 1633066 TI - Effects of a non-absorbable osmotic load on drug absorption in healthy volunteers. AB - 1. We have studied the effects of a non-absorbable osmotic load on the absorption of a multicomponent solution of frusemide, atenolol, hydrochlorothiazide and salicylic acid in six healthy volunteers. 2. Each subject was studied on up to four separate occasions. The drugs were administered in one of four solutions: a) a mannitol/electrolyte solution, b) a double-strength mannitol/electrolyte solution, c) a glucose/electrolyte solution and d) water. Lactulose or sulphasalazine were added as oro-caecal transit markers. Lactulose was included in the mannitol- and glucose-based solutions, adding a further non-absorbable osmotic load, and sulphasalazine was added to the water, adding little osmotic load. 3. The absorption of atenolol and hydrochlorothiazide was two- to three times less from all lactulose-containing solutions than from the sulphasalazine containing solution. The absorption of frusemide and salicylic acid was similar from all four solutions. 4. The largest non-absorbable osmotic load impaired the absorption of atenolol and hydrochlorothiazide most and the incorporation of glucose only partly restored absorption. 5. These results suggest that transmucosal water movement is an important determinant of atenolol and hydrochlorothiazide absorption but is less relevant for the absorption of frusemide and salicylic acid. Furthermore, these data demonstrate a previously unrecognised interaction between a commonly prescribed laxative--lactulose, and atenolol and hydrochlorothiazide. PMID- 1633065 TI - The influence of gastrointestinal transit on drug absorption in healthy volunteers. AB - 1. The effect of variability of gastric emptying and oro-caecal transit on the absorption of a multicomponent solution of frusemide, atenolol, hydrochlorthiazide and salicylic acid has been studied in six healthy subjects. Each subject was studied on five separate occasions: three times under basal conditions, once following metoclopramide and once following codeine pretreatment in an attempt to speed and slow transit respectively. 2. Inter-subject variability of gastric emptying, oro-caecal transit and the rate and extent of drug absorption was considerable. 3. The absorption of salicylic acid appeared rate-limited by gastric emptying but the rate and extent of frusemide, atenolol and hydrochlorthiazide absorption were unrelated to measures of gastric emptying or oro-caecal transit. 4. Codeine phosphate caused a two-fold delay in oro-caecal transit but did not influence gastric emptying while metoclopramide had no significant effect on either function. 5. Metoclopramide and codeine had no significant effect on the rate or extent of absorption of any of the study drugs. 6. Within the limits of this experiment, oro-caecal transit time did not appear to be an important determinant of frusemide, atenolol, hydrochlorothiazide or salicylic acid absorption. Other factors must account for the observed variability in drug absorption. PMID- 1633067 TI - Discrepancy between bioavailability as estimated from urinary recovery of frusemide and total diuretic effect. AB - 1. Frusemide was given at a dose of 60 mg as two oral controlled release (CR) formulations and as plain tablets in a randomised, balanced, three way cross over design to 26 healthy volunteers. Urinary volume, and contents of frusemide, sodium, chloride and potassium were measured in samples taken over 24 h. 2. There was a marked difference between the CR formulations on one hand and the plain tablets on the other, in excretion of frusemide and diuresis vs time. The total diuretic/saluretic effect was only marginally lower (19 and 28% respectively, P less than 0.05) after CR compared with plain tablets although the fraction absorbed was markedly decreased (39 and 51% lower, respectively, P less than 0.05), estimated as urinary recovery of frusemide. The total diuresis of the two CR formulations did not differ although the urinary recovery was significantly different (P less than 0.05). 3. The diuretic effect vs frusemide excretion rate showed minimal counter-clockwise hysteresis after plain tablets while the CR formulations produced clockwise hysteresis indicating tolerance. 4. In agreement with the concept of efficiency, the higher diuretic/saluretic effect per amount of excreted frusemide may be a consequence of the slower output of frusemide in urine with the CR formulations compared with plain tablets. The major part of the pharmacological effect was produced with a higher efficiency after CR compared with plain tablets. It should be noted that the pharmacokinetics of a drug and its pharmacodynamic potency independently determine the total response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1633068 TI - The influence of renal function on the renal clearance of morphine and its glucuronide metabolites in intensive-care patients. AB - 1. The relationships between renal creatinine clearance and the renal clearances of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were studied in fifteen intensive-care patients who were receiving morphine sulphate by constant intravenous infusion and who had diverse renal function. 2. An arterial blood sample was collected before and after a 4-5 h urine collection. Plasma and urine concentrations of morphine, M3G and M6G were measured by h.p.l.c. Plasma binding of all three compounds in drug-free plasma from healthy volunteers was determined by ultrafiltration. Measured renal creatinine clearance (CLCr,meas) was calculated from plasma and urinary creatinine concentrations (from h.p.l.c.). Also, creatinine clearance was predicted (CLCr,pred) from routine laboratory determination of plasma creatinine (Jaffe method). 3. There were significant linear relationships (P less than 0.001) between CLCr,meas and the renal clearances of morphine, M3G and M6G. The unbound renal clearance of morphine exceeded CLCr,meas (P less than 0.002) while the unbound renal clearances of M3G and M6G did not differ from CLCr,meas (P greater than 0.5). 4. In ten of the patients who received a constant infusion of morphine for at least 6 h, the dose-normalised plasma concentrations of M3G and M6G increased with decreasing CLCr,pred. Significant (P less than 0.001) relationships were observed between the reciprocal of CLCr,pred and the dose-normalised plasma concentrations of M3G and M6G. 5. The results indicate the importance of renal function in determining the renal clearances and plasma concentrations of M3G and M6G during intravenous infusion with morphine in intensive-care patients. PMID- 1633069 TI - Enhancement of the oral absorption of cyclosporin in man. AB - 1. The oral absorption of cyclosporin from three new semi-solid oral formulations was compared with the standard soft gelatine preparation in twelve healthy male volunteers. One formulation was based on a solid micellar solution, while the other two, with different in vitro release properties, were based on a microemulsion principle. 2. The results showed that the solid micellar solution and the faster releasing microemulsion formulation increased the extent of absorption on average by 45.2 and 49.0%, respectively, compared with the reference soft gelatine capsule. PMID- 1633070 TI - Contrasting effects of fluconazole and ketoconazole on phenytoin and testosterone disposition in man. AB - Nine healthy male subjects received oral fluconazole 400 mg daily, ketoconazole 200 mg twice daily or no treatment for 6 days according to a randomized, cross over design. A single 250 mg oral dose of phenytoin suspension was administered on day 5 and serum phenytoin concentrations were measured over the following 48 h. Serum testosterone concentrations were measured for 10 h after each dose of phenytoin. Ketoconazole had no significant effect on phenytoin concentrations while the mean AUC(0,48) for phenytoin was significantly higher with fluconazole (195.2 +/- 47.8 micrograms ml-1 h) than control (146.3 +/- 49.6 micrograms ml-1 h). At 48 h, the serum phenytoin concentration averaged 1.72 micrograms ml-1 under control conditions and 3.99 micrograms ml-1 with fluconazole (132% increase). AUC(0,10) for testosterone was 42% lower than control after ketoconazole administration (P less than 0.05) but increased by 33% from 55.6 +/- 9.4 ng ml-1 h (control) to 73.8 +/- 12.6 ng ml-1 h with fluconazole. AUC(0,10) values for the testosterone precursors androstenedione and 17 alpha hydroxyprogesterone were significantly higher in the fluconazole treatment phase as were concentrations of luteinizing hormone. The mechanism and clinical significance of the increase in testosterone concentration caused by fluconazole remains to be determined. PMID- 1633071 TI - Plasma and cerebrospinal fluid concentrations of paracetamol after a single intravenous dose of propacetamol. AB - Since the antipyretic and probably the analgesic effects of paracetamol are, at least in part, centrally mediated, its plasma and cerebrospinal fluid (CSF) concentrations were measured in 43 patients with nerve-root compression pain. Each subject was given a short i.v. infusion of 2 g propacetamol, a prodrug which is hydrolysed to paracetamol within 7 min. Single blood and CSF samples were drawn concomitantly in each patient at intervals between 20 min and 12 h. Maximum CSF drug concentrations were observed at the 4th hour, subsequent concentrations exceeding those in plasma. The elimination half-life of paracetamol calculated from pooled data was shorter in plasma (2.4 h) than in CSF (3.2 h). The time course of paracetamol in CSF may parallel that of analgesic effect. PMID- 1633072 TI - Update on nitrate tolerance. AB - 1. It is now recognised that nitrate therapy designed to provide effects throughout 24 h each day induces tolerance. Such tolerance may be partial or complete and is associated with diminished haemodynamic and clinical effects. 2. The mechanism of tolerance is not completely understood but it seems to be related to the depletion of reduced sulphydryl groups in vascular smooth muscle and to the activation of counter-regulatory forces. These include elevated plasma catecholamines, arginine vasopressin and plasma renin activity. Activity of the renin-angiotensin system is associated with sodium and water retention and plasma volume expansion. The increase in vasoconstrictor influences and augmented plasma volume could modulate the effect of nitrate-induced vasodilatation. PMID- 1633073 TI - Plasma profile and haemodynamic tolerance to isosorbide-5-mononitrate in controlled-release form. AB - 1. Plasma concentrations and some haemodynamic parameters known to be affected by nitrates, were monitored in healthy volunteers who received three different dose regimens of isosorbide-5-mononitrate (5-ISMN) over 5 day study periods. 2. No haemodynamic tolerance was found in the 60 mg once-daily dose schedule which produced high plasma concentrations during the daytime but concentrations no greater than 100 ng ml-1 at night. In contrast, a dose regimen of 60 mg followed by 30 mg 12 h later and thereafter every 8 h until the fifth day induced complete haemodynamic tolerance. With this dose regimen the minimum plasma concentrations were never below 300 ng ml-1. A significant attenuation of haemodynamic effects was also found with the third dose regimen, 60 mg followed by 30 mg 6 h later for 5 days, which produced minimum plasma concentrations of between 100 ng ml-1 to 300 ng ml-1; the degree of attenuation rose as trough plasma concentrations increased. 3. In conclusion, 60 mg 5-ISMN in a controlled-release (Durules) preparation given once daily was the only dose regimen not inducing nitrate tolerance. PMID- 1633074 TI - Prophylactic nitrate therapy in angina pectoris--is there an optimal treatment regimen? AB - 1. Nitrates have a place in the prophylactic treatment of patients with angina pectoris. Their efficacy is not in doubt. 2. However, there may be some practical problems associated with their use, such as unreliable absorption, short duration of action, treatment-induced headache, development of nitrate tolerance and a suggested rebound phenomenon observed during intermittent dosing. Furthermore, patient convenience with treatment schedule and patient compliance have to be considered during prophylactic treatment. The present article discusses how many of these problems may be solved by selection of formulation as well as nitrate compound. 3. The development of controlled-release formulations producing sufficiently high nitrate plasma concentration during part of the day followed by nitrate-poor rather than nitrate-free interval, have the potential to prevent both nitrate tolerance and rebound phenomenon, and produce a sufficiently long duration of action with a convenient once daily regimen. PMID- 1633075 TI - Effects of nitrates on mortality in acute myocardial infarction and in heart failure. AB - 1. Seven randomized controlled trials of intravenous nitroglycerin in a total of about 850 patients have been reported. Overall, there were 51 deaths (12.5%) in the nitroglycerin group and 87 (20%) in the control group. This indicates a 48% reduction in the odds of death (P less than 0.001, 95% confidence limits (25% to 64%)). 2. There are five randomized trials of oral nitrates after acute myocardial infarction. In these trials, 11.8% of the patients in the nitrate group compared with 13.3% in the control group died. This indicates a nonsignificant 12% reduction in the odds of death but the 95% confidence interval overlaps widely with the i.v. trials. If all trials of i.v. or oral nitrates are considered the reduction in the odds of death is 32% (P less than 0.01). 3. Nitrates have a beneficial effect on haemodynamics in heart failure but the data on mortality effects are sparse. In combination with hydralazine, however, long term mortality was reduced in the V-HEFT trial of chronic heart failure. PMID- 1633077 TI - Nitrates today and tomorrow: introduction. PMID- 1633076 TI - Endogenous and exogenous nitrates and their role in myocardial ischaemia. AB - 1. Although nitrates have been prescribed in patients with angina pectoris for more than a century, their mechanism of action has only been understood recently. 2. The discovery of the endogenous nitrovasodilator nitric oxide, which is formed in endothelial cells by the enzyme nitric oxide synthase, has greatly expanded our knowledge. Nitric oxide, if released from endothelial cells can interact with vascular smooth muscle as well as circulating blood cells such as platelets. Nitric oxide activates soluble guanylate cyclase, which in turn leads to an intracellular increase in cyclic GMP. In vascular smooth muscle, this causes vasorelaxation, in platelets dysaggregation and prevention of platelet adhesion. This protective pathway both reduces the effects of vasoconstrictor substances, can produce profound vasodilation, if activated appropriately and acts as a regulator of platelet-vessel wall interaction. In addition, nitric oxide inhibits the production and action of endothelin, a 21 amino acid vasoconstrictor peptide formed by endothelial cells. 3. Exogenous nitrovasodilators also exert their action by releasing nitric oxide from the molecule. Their action is particularly pronounced in blood vessels with a low basal production of nitric oxide and is enhanced after removal of the endothelium. In coronary artery disease, the formation of endothelium-derived nitric oxide is reduced, its breakdown is increased, but only at later stages, is the action of endogenous and therapeutic nitrates depressed. 4. Hence, nitrates are an appropriate therapeutic tool in patients with coronary artery disease to substitute the effects of the impaired activity of the endothelial L-arginine/nitric oxide pathway. PMID- 1633080 TI - Expanded programme on immunization (EPI). Progress towards poliomyelitis eradication. PMID- 1633079 TI - Do nitrates differ? AB - 1. The organic nitrates all share a common biochemical and physiological mechanism of action. 2. The organic nitrates differ substantially in their pharmacologic potency and pharmacokinetics. In vitro potency differences appear larger than the corresponding in vivo activities. 3. The duration of action of organic nitrates, after a single immediate-release dose, is governed by the pharmacokinetics of the drug. However, the duration of action of available sustained-release preparations, whatever the nitrate or formulation, is limited to about 12 h, due to the development of pharmacologic tolerance. 4. Nitrates do not appear to differ in their production of undesirable effects. PMID- 1633078 TI - Clinical relevance of endothelium-derived relaxing factor (EDRF). AB - 1. In addition to metabolic and neurohumoral factors endothelium-derived autacoids like the nitric oxide radical NO and prostacyclin are effective regulators of vascular tone and thus tissue perfusion. NO is produced in endothelial cells from L-arginine by a Ca2+/calmodulin-dependent enzyme NO synthase. In addition, the NO radical is ultimately cleaved from all nitrovasodilators and resembles their vasoactive and antiaggregatory principle, which is used under pathological conditions as substitution therapy for impaired endothelial function and autacoid production. Impaired endothelium-dependent vasomotor control has been documented in hypercholesterolaemia, atheromatosis, diabetes, hypertension, and in reperfusion damage. L-arginine supplementation is effective in a few instances. PMID- 1633082 TI - Continuing education: opening up on education. PMID- 1633081 TI - Clinical enteral nutrition [continuing education credit]. AB - There are many reasons why an individual may become malnourished. It is important for nurses to be able to recognise people at risk, and to understand the processes that will safeguard their nutritional status in hospital and in the community. PMID- 1633083 TI - Homelessness: exploding a modern myth. Interview by Charlotte Alderman. PMID- 1633084 TI - Extended role: taking a giant leap towards freedom. PMID- 1633085 TI - Intensive care: pulmonary artery pressure monitoring. AB - Pulmonary artery pressure monitoring is an important aspect of the nurse's role in intensive care units. This article describes the advantages such monitoring can offer in the assessment of critically ill patients, and some of the common problems nurses face when using the specialised equipment. PMID- 1633086 TI - Analysing mandatory continuing education. AB - Of all the contentious issues surrounding the United Kingdom Central Council's continuing education proposals, the introduction of mandatory continuing education is perhaps the most controversial. This article sets out the issues surrounding it, including the postulated infringement of the voluntary principles of adult education, the effect it has on the learning process, and the possibility of it leading to uniform and inferior learning. The main issue, however, is whether mandatory continuing education achieves its objective of enabling staff to improve their practice. More research is required, the author argues, before this crucial question can be answered. PMID- 1633087 TI - Oral candidiasis and HIV infection. AB - Helping patients cope with the unpleasant symptoms of oral candidiasis is among the many challenges facing nurses caring for people with HIV infection. The features, treatment and prevention of this distressing condition are described. Nurses are identified as having a major part to play in educating patients to manage the symptoms. PMID- 1633088 TI - Reviewing the nurse-patient partnership. AB - One of the vital components of contemporary professional nursing is the idea of nurses working in 'partnership' with patients. In an effort to establish a framework for examining the concept of partnership and how this is viewed and utilised by the profession, a formal review of the literature relevant to this area was undertaken. British and overseas journals and also textbooks of nursing from the UK and the USA were reviewed. The results of the review are discussed in an effort to offer some clarity to this somewhat complex concept. PMID- 1633089 TI - Should employers be given the chance to remedy poor standards of care before a whistleblower goes public? PMID- 1633090 TI - Dual-needs provision: everybody else's client. PMID- 1633091 TI - Breaking professional barriers. PMID- 1633092 TI - The Clay column. PMID- 1633093 TI - Care of elderly people. Thoughts from a train. PMID- 1633094 TI - Care of elderly people. Carer support: it's up to us. PMID- 1633096 TI - Care of elderly people. 'I've got to see Angie'. PMID- 1633095 TI - Care of elderly people: a change of scene. PMID- 1633097 TI - LED perimeter for visual field analysis by mapping of small field evoked potentials. AB - A new type of visual field perimeter, equipped with conic light emitting diodes (LEDs) located at 10 degrees intervals automatically programmable is described. The device is meant for visual field analysis by mapping of the evoked responses derived from the retina and specific cortical projection areas. PMID- 1633098 TI - Mapping of VEPs and ERG responses to punctual stimulations in the visual field. AB - Visual field projection maps were obtained using retinal and cortical EP amplitude values. Single meridian investigations were also performed. Stimulation was done with punctual photic stimuli delivered by the LED perimeter built for the purpose. Schedule with 28 stimulation loci was adopted. The B wave of the average ERG and P100 component of the cortical VEP were measured. The maps were obtained by interpolation of amplitude values on a grid of 21 x 21 characters. By comparing the retinal and cortical visual field maps, conclusions regarding the normality of visual structures (peripheral or central) can be drawn. Our procedure adds to the previous data on visual field investigation (cynetic or static) important elements concerning vision electrophysiology. PMID- 1633099 TI - Advances in the pathogeny of migraine. PMID- 1633100 TI - Vocabulary grammatical structure in aphasic patients. AB - In 10 aphasics (7 Broca's and 3 Wernicke's) of vascular etiology and 10 normal controls, a corpus of 2,500 words was selected in each subject by means of a standard interview. The 10 grammatical classes of the Romanian language were studied. The vocabulary reduction observed in aphasics was produced by the loss of nouns, adjectives and verbs. In exchange, proportionally to their vocabulary, they used more adverbs, pronouns and numerals than the normals. Articles, prepositions and conjunctions showed a similar use with that of the normals. The aphasic patients preserved basic words for each part of speech, the loss of vocabulary operated among the non-basic words. It was revealed by the Token-Type ratio that the verbal creativity was lower in aphasics than in controls. However, in normals as in aphasics verbal creativity was higher in the non-basic words than in the basic ones. The results are discussed by the action of different factors as: the semantic and syntactical constraints, semantic characteristics and syntactical functions proper to each class as well as the influence of the different amounts of words comprised in each grammatical class on the selection of the necessary word. PMID- 1633101 TI - Type and frequency of phonetic errors in aphasics: therapeutic aspects. AB - Fifty aphasics were studied in three separate groups: nonfluent Broca, fluent Wernicke and fluent anomics in order to form a therapeutic guide of their phonetic errors (omission substitution, addition, repeated phonemes, perseveration of phonemes belonging to the preceding word, reversed order, phonematic targetting and misplacing. Frequency of phonetic error was also assessed. PMID- 1633102 TI - Serum immunoglobulin levels in schizoaffective disorders (manic and depressive). AB - Immunoglobulin levels (A, G, M) were measured with Mancini's radial immunodiffusion technique (RID). IgA and IgG levels showed a statistically significant increase in schizoaffective patients compared to normals, and schizophrenics, but no modification in comparison with the affective patients. IgM also showed a statistically significant increase which may constitute a trait marker for the schizoaffective disease. PMID- 1633103 TI - Modalities of collateral supply of cerebral circulation through the circle of Willis in stenoses and occlusions of extracranial carotid arteries. AB - The intracranial cerebral circulation was studied in 6 patients with bilateral ischemic lesions due to lesions of the internal carotid artery in the extracranial segment (2 significant bilateral stenosis cases; 1 case with bilateral thrombosis and 3 cases of unilateral thrombosis and significant controlateral stenosis). All the patients were males their age ranging between the 5th and 8th decades of life. In a single case, the neurological examination showed secondary left hemiplegia and recent right paresis of remittent type whereas the other 5 patients had only transient ischemic attacks with hemiparesis or transient aphasia. The lesions were revealed by duplex system echotomography (Aloka-Hellige Model SSD-630) and spectral analysis of Doppler signal (Vasoscan Sonicaid) and were later confirmed by bilateral carotid arteriography in all patients. The intracranial circulation was also watched by noninvasive methods using the spectral analysis of the Doppler signal with pulsed wave on TC-2 64-B apparatus. As for the modalities of blood flow compensatory mechanisms by the circle of Willis, it may be noted that in none of the patients investigated did the collateral supply observe a "mathematical model". PMID- 1633104 TI - The influence of trauma on the proliferating potential in neurofibromatosis. Case report. PMID- 1633105 TI - NSCL-2: a basic domain helix-loop-helix gene expressed in early neurogenesis. AB - We have identified a new basic domain helix-loop-helix (bHLH) gene, NSCL-2, which was cloned because of its homology to the previously described putative hematopoietic transcription factor, SCL. NSCL-2 has been identified in both human and murine DNA. NSCL-2 complementary DNA clones were obtained from an 11.5-day murine embryo library. The coding region is 405 base pairs and encodes a predicted protein of 15.6 kilodaltons. There is 74% homology at the nucleotide level with the coding region of the murine SCL and 27% protein homology. Unlike the majority of previously described bHLH genes, the NSCL-2 coding region ends only six amino acids beyond the second amphipathic helix of the HLH domain. The NSCL-2 gene shows a markedly restricted pattern of expression predominantly confined to murine embryos at days 11-13 of development, although low level expression can be detected in murine embryos flanking this time point. Examination of 11- and 12-day mouse embryos by tissue in situ hybridization reveals expression of NSCL-2 in the developing nervous system, most likely in developing neurons. The NSCL-2 gene maps to murine chromosome 3. The temporally and tissue restricted pattern of expression of this gene and its identification as a member of a family of transcription factors relevant to growth and development in a wide variety of species suggest a role for NSCL-2 in the development of the eukaryotic nervous system. PMID- 1633106 TI - Cell type and differentiation dependent heterogeneity in retinoblastoma protein expression in SCID mouse fetuses. AB - The expression pattern of retinoblastoma (Rb) protein has been studied at the single cell level in frozen sections of 16- to 18-day-old SCID mouse fetuses by immunofluorescence staining with mouse monoclonal and rabbit polyclonal antibodies, using conventional epifluorescence and confocal laser scanning microscopy. The nuclei of megakaryocytes, hemopoietic islands of the fetal liver, osteo-, amelo-, and odontoblasts, and skeletal muscle were strongly stained. There was no detectable Rb staining in the basal cell layers of stratified squamous epithelia, but the differentiating, more superficial layers were positive. Intestinal crypts were negative, whereas the villi were positive. In the retina, Rb protein was detectable in the inner ganglion layer but not in the outer neuroblastic layer. In the central nervous system, Rb protein was present in neurons and glia cells as well. The nuclei in the collecting tubules of the kidney, the pancreas, and the adrenal cortex were Rb positive. Analysis of the differentiation dependent expression of Rb protein in relation to the prospective life cycle of the cells in which it appears may pave the way toward an understanding of the tissue specific oncogenic effect of Rb loss in families with hereditary retinoblastoma. PMID- 1633107 TI - mmCGM1a: a mouse carcinoembryonic antigen gene family member, generated by alternative splicing, functions as an adhesion molecule. AB - Carcinoembryonic antigen is a human tumor marker and the prototype of a large family of immunoglobulin-like proteins. We have been developing a mouse model for this large protein family and have cloned a complementary DNA (cDNA) for a mouse carcinoembryonic antigen gene family member (mmCGM1a). Two transcripts expressed in several different adult mouse tissues hybridize to this cDNA, a 1.8-kilobase and a 4.6-kilobase mRNA. Sequences of many related cDNA clones indicate that they are most likely encoded by a single gene which undergoes alternative splicing. The protein encoded by the mmCGM1a cDNA shares 69% of the amino acid residues in the NH2-terminal domain with a rat liver ecto-ATPase and with the human biliary glycoprotein. Mouse fibroblast transfectant cells expressing the mmCGM1a protein on their cell surface exhibit calcium- and temperature-independent adhesion in vitro which can be specifically inhibited by an antibody raised against a carcinoembryonic antigen-related 120 kilodalton protein. PMID- 1633108 TI - Anti-immunoglobulin treatment of murine B-cell lymphomas induces active transforming growth factor beta but pRB hypophosphorylation is transforming growth factor beta independent. AB - Cross-linking of B-cell membrane immunoglobulin (Ig) receptors induces growth arrest at G1-S, leading to apoptosis and cell death in the immature lymphomas WEHI-231 and CH31, but not in the CH12 B-cell line. In this system, which has been used as a model for B-cell tolerance, we have established that these lymphomas produce active transforming growth factor beta (TGF-beta) when treated with anti-Ig and that their hierarchy of sensitivity to TGF-beta generally correlates with their growth inhibition by anti-Ig. TGF-beta, in turn, has been shown to interfere with the phosphorylation of the retinoblastoma gene product, pRB. Herein, we also demonstrate that in WEHI-231 B-lymphoma cells treated with anti-Ig for 24 h, the pRB protein is found to be predominantly in the underphosphorylated form, as previously reported for cells arrested by the exogenous addition of TGF-beta. However, neutralizing antibodies to TGF-beta failed to prevent growth inhibition by anti-Ig in WEHI-231 and CH31. When WEHI 231 lymphoma cells were selected for growth in TGF-beta, the majority of the TGF beta-resistant clones remained sensitive to anti-Ig-mediated growth inhibition. In these clones, the retinoblastoma gene product was found to be in the underphosphorylated form after 24-h treatment with anti-Ig, but not with TGF beta. These data show that anti-Ig treatment of murine B-cell lymphomas stimulates the production of active TGF-beta but that a TGF-beta-independent pathway may be responsible for the pRB underphosphorylation and cell cycle blockade. PMID- 1633109 TI - Regions within the c-Myc protein that are necessary for transformation are also required for inhibition of differentiation of murine erythroleukemia cells. AB - The c-, L-, and N-Myc nuclear phosphoproteins share several highly conserved regions that partially overlap putative functional domains of the c-Myc protein. All three myc oncogenes can cooperate with an activated ras gene to transform primary rat embryo cells (REC), and deregulated expression of c- and L-myc can block differentiation of murine erythroleukemia (MEL) cells. In the present study, we demonstrate that N-myc also can block MEL cell differentiation, and we identify regions within the c-Myc protein that are necessary for inhibition of MEL differentiation. C19 MEL cells were transfected with six human c-myc genes which were partially deleted in different areas of the coding region. Four of the genes lack sequences that overlap either the putative transcriptional activation domain, the helix-loop-helix motif, or the leucine zipper motif and were previously shown to have lost REC cotransforming activity (J. Stone, T. DeLange, G. Ramsay, E. Jakobovitz, J.M. Bishop, H. Varmus, and W. Lee, Mol. Cell. Biol., 7: 1697-1709, 1987). In this study, we demonstrate that they also fail to inhibit N,N'-hexamethylene-bis-acetamide-induced differentiation of MEL cells. In contrast, two partially deleted c-myc genes, one lacking a short NH2-terminal region and the other lacking 118 amino acids at the center of the coding region, which were fully active in REC cotransformation, also exhibited full activity associated with the former and only partial activity with the latter in blocking MEL differentiation. We conclude that the mutated genes tested in this study behave similarly in inhibition of MEL cell differentiation and in REC cotransformation. PMID- 1633110 TI - Complex expression of the genes coding for plasminogen activators and their inhibitors in HeLa-smooth muscle cell hybrids. AB - As cells progress through the multistep process of neoplastic transformation, they eventually acquire the property of invasive behavior. Although both plasminogen activators (PA) and their inhibitors (PAI) contribute to this process, their regulation in normal and transformed cells remains poorly defined. Because somatic cell hybrids provide useful tools for examining the transformation pathway, tumorigenic and invasive HeLa cells were fused with human normal vascular smooth muscle cells and tested for invasion-related parameters, including the expression of PA and PAI genes, and matrix degradation. Both parental cell lines produced large amounts of PAI activities with no detectable PA in either cellular or secreted form. Opposite findings were obtained with the hybrid cell lines, which demonstrated the presence of receptor-bound and secreted PA but absence of enzymatically measurable PAI activities. Both urokinase-type and tissue-type PA were found in cell-associated and secreted form in the hybrid cells. In addition, expression of the urokinase-type PA receptor gene was found in the three hybrid cells and the vascular smooth muscle cells but not in the HeLa cells. Expression of active, receptor-bound and secreted PA provided the nontumorigenic hybrid cells with the enzymatic tools to degrade extracellular proteins in a plasminogen-dependent manner. Thus, the hybrid cells lost tumorigenicity while retaining the tissue-degrading capability of HeLa cells. These hybrid cell lines should prove to be important reagents for investigating the complex regulatory control of PA and PAI gene expression. PMID- 1633111 TI - Transforming growth factor beta 1 regulation of c-myc expression, pRB phosphorylation, and cell cycle progression in keratinocytes. AB - Transforming growth factor beta 1 (TGF-beta 1) is a potent inhibitor of cellular proliferation in a variety of cell types, including skin keratinocytes. TGF-beta 1 suppression of c-myc transcription has been implicated in the mechanism of TGF beta 1 inhibition of keratinocytes, and evidence suggests that the protein product of the retinoblastoma gene (pRB) is a necessary component in this pathway. Following growth factor stimulation of quiescent keratinocytes, TGF-beta 1 can inhibit cell cycle progression into S phase at any point prior to the G1-S transition but does not inhibit progression through the S phase of the cell cycle. Since pRB is hypophosphorylated during G1 and hyperphosphorylated during S and G2, the G1-S-specific phosphorylation of pRB becomes an attractive target for the growth-inhibitory activities of TGF-beta 1. However, in TGF-beta 1-treated primary human keratinocytes and in a series of human papilloma virus and SV40 immortalized human keratinocyte cell lines, the phosphorylation status of pRB strictly correlated with cell growth. No evidence was found for a direct effect of TGF-beta 1 on the phosphorylation state of pRB in these cells. It was further demonstrated that synthesis of c-myc protein can be rapidly inhibited by TGF-beta 1 addition throughout G1 and S phases, indicating that the phosphorylation state of pRB, at least as it varies during the cell cycle, does not alter the ability of TGF-beta 1 to suppress c-myc expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1633112 TI - Shift from posttranscriptional to predominant transcriptional control of the expression of the GM-CSF gene during activation of human Jurkat cells. AB - The expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene is differentially regulated in various cell types. We investigated the mechanisms controlling its expression in 12-O-tetradecanoylphorbol-13-acetate plus phytohemagglutinin-stimulated Jurkat cells, a human T-cell line. In unstimulated cells, GM-CSF mRNA was undetectable by Northern blot. Upon activation, it was detected from 3 h onward, with a progressive increase in the levels of the transcript up to 24 h of stimulation. Whereas cycloheximide treatment at the time of stimulation blocked mRNA induction, its addition at later times resulted in a marked increase in transcript levels. Run-on analysis showed that transcription of the GM-CSF gene was low to undetectable in unstimulated cells; stimulation led to transcriptional activation, which was weak at 6 h but had increased 16-fold at 24 h. In addition, the mRNA half-life decreased during activation, from 2.5 h at 6 h down to 45 min at 24 h. Cycloheximide treatment increased GM-CSF mRNA half-life (3- and 4-fold, respectively). Our results show: (a) both transcriptional and posttranscriptional signals regulate GM-CSF mRNA levels in activated Jurkat cells, (b) de novo protein synthesis is required for mRNA induction, whereas destabilizing labile proteins control the transcript stability, and (c) a shift from a posttranscriptional to a predominant transcriptional control of GM-CSF gene expression occurs during activation. PMID- 1633113 TI - Regulation of EGR-1, c-jun, and c-myc gene expression by oncostatin M. AB - Oncostatin M (OM) is a cytokine that shares a structural and functional relationship with interleukin 6, leukemia-inhibitory factor, and granulocyte colony-stimulating factor. In this report, we tested for correlations between immediate-early gene expression and some of the cellular responses elicited by OM. We determined that OM stimulated a rapid and transient elevation of EGR-1, c jun, and c-myc mRNA in human fibroblasts prior to their proliferation. OM also stimulated a transient induction of these genes in M1 leukemic cells that differentiated into nonreplicating, macrophage-like cells. The expression of c myc, however, decreased significantly as the cells stopped dividing. Interestingly, OM had no detectable effect on the expression of EGR-1, c-jun, and c-myc during the cell cycle arrest of human A375 melanoma cells. Our results indicate that an early nuclear event associated with OM action is the regulation of immediate-early gene expression. We suggest that the transcription factors encoded by the EGR-1, c-jun, and c-myc genes are utilized in both cell proliferation and differentiation but are not part of the mechanism by which OM inhibits A375 cell growth. PMID- 1633114 TI - Regulation of epidermal growth factor receptor gene expression in murine embryonal carcinoma cells. AB - The protooncogene c-erbB1 [epidermal growth factor receptor (EGF-R)] is expressed in a wide variety of cell types and in most adult tissues. The precise roles of the EGF-R in vivo are largely unknown, especially their role in growth and development of embryonic tissues. We reported earlier that EGF-Rs are not expressed on the cell surface of undifferentiated embryonal carcinoma (EC) cells, but intracellular receptor protein is detectable (A. Weller, J. Meek, and E. D. Adamson, Development, 100: 351-363, 1987). We document here that in embryonal carcinoma cells, low levels of both receptor mRNA and protein are observed, but after 4 days of retinoic acid-induced differentiation, large increases are seen. Most notable is the 35-70-fold rise in the levels of EGF-R transcripts during the differentiation of P19 embryonal carcinoma cells to neural and glial cells, and this is paralleled by a 10-fold rise in protein. Measurements of the degradation rates of EGF-R mRNA and receptor protein show that both are rather stable and may partially explain the steady-state increases during differentiation. Run-on transcription assays of the EGF-R gene show very low rates of transcriptional activity at all stages: about 2-fold changes in transcription rate can be detected. It is concluded that transcriptional mechanisms may also partially account for increased levels of gene products. We hypothesize that the appearance of EGF-Rs at the cell surface leads to the slow induction of further receptor levels by EGF/transforming growth factor alpha stimulation, and this contributes to the driving force of differentiation and to the stability of the differentiated state. PMID- 1633115 TI - The ets gene family. PMID- 1633116 TI - Therapeutic strategies and outcomes: perspectives from different cultures. AB - Two forms of psychological therapy, one Japanese the other Euro/American, are described and compared. It is suggested that each identifies comparable goals for individual change. However, each differs in the means by which change is induced. The consensus concerning goals is taken as evidence of universal values in the definition of the fully functioning self. However, the divergence in means by which these goals are attained reflects specific cultural differences. The implications of these differences are related to individualistic versus relational values within the cultures discussed. It is proposed that the comparisons have implications for the practice of any specific form of psychotherapy on members of a culture other than that within which the therapy has developed. PMID- 1633118 TI - Sense of self in recovery from severe mental illness. AB - This report based on research interviews conducted with persons struggling to recover from prolonged psychiatric disorders suggests that the rediscovery and reconstruction of an enduring sense of the self as an active and responsible agent provides an important aspect of improvement. This process of developing a functional sense of self in the midst of persisting psychotic symptoms and dysfunction is described, and its implications for understanding severe mental illness and processes of change are discussed. It is suggested that viewing the development of a dynamic sense of self as central to the improvement process provides a coherent thread which ties together diverse research findings concerning factors influencing course and outcome of illness. It is also suggested that for treatment and rehabilitation to elicit and foster a more functional sense of self, models of improvement will need to allow for, and encourage, a more active and collaborative role for the person with the disorder. PMID- 1633117 TI - The belief in the transmigration of souls: psychotherapy of a Druze patient with severe anxiety reaction. AB - In this paper the culture-sensitive psychotherapy of a 19-year-old Druze patient with severe anxiety reaction is described. The patient explained his anxiety and his symptoms as stemming from violent death in his former life and subsequent transmigration. The therapists joined the patient's explanatory model and previous traditional healing, adding hypnotic suggestion which relieved the symptoms. The relationship of patient symptomatology to cultural background, multiple personality disorder, possession and dissociation is discussed. The strategic combination of culture-specific and modern psychiatric approaches is advocated in similar cases. PMID- 1633119 TI - Therapy factors in treating severely ill psychiatric patients. AB - We studied therapeutic factors influencing suicide during out-patient treatment in severely ill discharged psychiatric in-patients. A subsample of 25 suicide and 27 control patients were all treated by psychiatrists at the time of their suicide or at a corresponding point of time. We were not able to identify any significant psychosocial or clinical pre-discharge differences between the two groups. After discharge, the patients of the control group were treated by psychiatrists with substantially longer professional training-plus-experience, the therapist's experience being the most important therapy factor contributing to the different outcome. On the whole, the contribution of the therapy factors was modest, however, explaining only 26 per cent of the group variance. PMID- 1633120 TI - Structural equation modelling of some of the determinants of suicide risk. AB - Much of the psychological research with suicidal patients has examined, individually or in combination, correlates and predictors of the various measures in the suicide process. The present study investigated suicidal risk as an outcome measure. Several questionnaires were administered to a sample of 94 soldiers, 61 of whom had manifested some suicidal symptoms. Using LISREL analysis, the data showed that the best model had suicide risk as directly influenced by depression and indirectly by impulsivity. PMID- 1633121 TI - How specific are negative automatic thoughts to a depressed population? An exploratory study. AB - This paper is concerned with the relationship between negative or dysfunctional automatic thoughts and dysphoric mood in a non-clinical population. It addresses the question of how specific are these automatic thoughts to a depressed population. Negative automatic thoughts were obtained from 27 normal subjects via a thought-sampling method using the Daily Record of Dysfunctional Thoughts Form (Beck, Rush, Shaw & Emery, 1979) over a two-week period. A thought-content analysis was conducted. The resultant data were compared using X2 with Blackburn & Eunson's (1989) data from depressed patients. The results presented in this paper indicate that basic cognitive distortions occur in a normal population, but differ qualitatively and quantitatively from those found in depressed patients. PMID- 1633122 TI - Mood states and minor illness. AB - Mood and health reports from 65 administrative and clerical staff were obtained daily over a period of several weeks. Three mood factors emerged from the aggregated data which appear to be most suitably labelled: happiness, tense depression and hostile depression. Subjects high on hostile depression suffered more from colds. Subjects scoring highly on tense depressed mood reported more insomnia, head and neck aches. The results, especially in regard to hostile depression, are discussed in a wider context, including possible overlap with core affective aspects of the well-known Type A coronary risk construct. Finally, psychoimmunological interpretations of the link between hostile depression and vulnerability to colds are considered. PMID- 1633123 TI - Beliefs and fears underlying the Type A behaviour pattern in adolescents. AB - The present study was designed to test Price's (1983) cognitive social learning model of Type A in an adolescent population. A questionnaire measuring beliefs and fears thought to underlie Type A together with two measures of Type A (the Bortner scale and the student version of the Jenkins Activity Survey, SJAS) were administered to over 300 adolescents. Results showed that subscales measuring Type A beliefs and fears had acceptable levels of internal reliability and formed two separate components (beliefs and fears). Measures of beliefs and fears correlated significantly but modestly with measures of Type A thus providing some support for Price's cognitive social learning model. Furthermore, some striking sex differences were found. Results are discussed in terms of the implications of these beliefs and fears in studying the Type A behaviour pattern in children and adolescents and the modification of the behaviour pattern in the younger population. PMID- 1633124 TI - The effect of olfactory stimulation on fluency, vividness of imagery and associated mood: a preliminary study. AB - Twenty-two subjects were asked to visualize positive and negative phrases following exposure to either chamomile oil or placebo. Chamomile oil significantly increased the latency for all images, and shifted mood ratings and frequency judgements in a more positive direction, suggesting a possible mode of action for such oils. PMID- 1633125 TI - The effect of pre-assessment information on clients' satisfaction, expectations and attendance at a mental health day centre. AB - An information sheet describing the nature of initial assessment sessions was sent to people referred to a mental health day centre. This study examines the effect of receiving the information on attendance at assessment, expectations of the session and subsequent satisfaction. A group of subjects who were sent the information were compared with a control group who were not. The former group were more likely to attend the initial appointment (82 per cent attended) than those who did not receive the information (57 per cent attended). Of those subjects who attended, the experimental group expressed greater satisfaction overall and with the session itself. There were no differences between the groups on other satisfaction measures, levels of state anxiety and expectations. It is concluded that the effect of the information sheet is most likely to be mediated by changes in satisfaction levels which may be raised by increased levels of personal attention. PMID- 1633126 TI - Psychoanalytic views of aggression: some theoretical problems. AB - Various problems in relation to psychoanalytic theories of aggression are considered in a review which is by no means exhaustive but includes areas which have puzzled and interested the author. First to be considered is why the concept of aggression as a major drive was a relative late-comer in psychoanalysis; next the contentious concept of a 'death instinct' and some of the factors in Freud's lifetime which may have contributed to both. Then it is suggested that we seem to have theories of aggression which might be called primary or secondary in two different senses. First is the question whether aggression is innate or secondary to frustration. In another sense, primary and secondary theories of aggression seem to survive paralleling Freud's original primary and secondary theories of anxiety. In this sense the primary theory survives as an explanation of psychosomatic disorder. Lastly, the link between suicide and murder is considered and the turning of aggression against the self in depression and self-destructive attacks. PMID- 1633127 TI - Effects of selective pressure block of Y-type optic nerve fibers on the receptive field properties of neurons in the striate cortex of the cat. AB - In an aseptic operation under surgical anesthesia, one optic nerve of a cat was exposed and subjected to pressure by means of a special cuff. The conduction of impulses through the pressurized region was monitored by means of electrodes which remained in the animal after the operation. The pressure was adjusted to selectively eliminate conduction in the largest fibers (Y-type) but not in the medium-size fibers (X-type). The conduction block is probably due to a demyelination and remains complete for about 3 weeks. Within 2 weeks after the pressure-block operation, recordings were made from single neurons in the striate cortex (area 17, area V1) of the cat anesthetized with N2O/O2 mixture supplemented by continuous intravenous infusion of barbiturate. Neurons were activated visually via the normal eye and via the eye with the pressure-blocked optic nerve ("Y-blocked eye"). Several properties of the receptive fields of single neurons in area 17 such as S (simple) or C (complex) type of receptive field organization, size of discharge fields, orientation tuning, direction selectivity indices, and end-zone inhibition appear to be unaffected by removal of the Y-type input. On the other hand, the peak discharge rates to stimuli presented via the Y-blocked eye were significantly lower than those to stimuli presented via the normal eye. As a result, the eye-dominance histogram was shifted markedly towards the normal eye implying that there is a significant excitatory Y-type input to area 17. In a substantial proportion of area 17 neurons, this input converges onto the cells which receive also non-Y-type inputs. In one respect, velocity sensitivity, removal of the Y input had a weak but significant effect. In particular, C (but not S) cells when activated via the normal eye responded optimally at slightly higher stimulus velocities than when activated via the Y-blocked eye. These results suggest that the Y input makes a distinct contribution to velocity sensitivity in area 17 but only in C-type neurons. Overall, our results lead us to the conclusion that the Y-type input to the striate cortex of the cat makes a significant contribution to the strength of the excitatory response of many neurons in this area. However, the contributions of Y-type input to the mechanism(s) underlying many of the receptive-field properties of neurons in this area are not distinguishable from those of the non Y-type visual inputs. PMID- 1633128 TI - Effects of selective pressure block of Y-type optic nerve fibers on the receptive field properties of neurons in area 18 of the visual cortex of the cat. AB - Recordings were made from single neurons in area 18 of anesthetized cats (N2O/O2 mixture supplemented by continuous intravenous infusion of barbiturate) in which one optic nerve had been pressure blocked to selectively block conduction in the largest (Y-type) fibers. Cortical neurons were stimulated visually via the normal eye or via the eye with the pressure-blocked optic nerve ("Y-blocked eye"). Several properties of the receptive fields such as their spatial organization (S or C cells), orientation tuning, and the presence and strength of end-zone inhibition appear to be unaffected by removal of the Y input. By contrast, the removal of the Y input resulted in a small but significant reduction in the size of the discharge field and in the direction-selectivity index. In three respects, peak response discharge rate, eye dominance, and velocity sensitivity, removal of the Y input had strong and highly significant effects. Thus, the mean peak discharge frequency of responses evoked by the stimulation of binocular neurons via the Y-blocked eye was significantly lower than that of responses evoked by the stimulation via the normal eye. Accordingly, the eye-dominance histogram was shifted markedly towards the normal eye (more so than in the homologous experiment conducted on area 17-Burke et al., 1992). Finally, the mean preferred velocity of responses of cells activated via the normal eye was in the vicinity of 145 deg/s, whereas for cells activated via the Y-blocked eye the value was about 35 deg/s. Overall, the results of the present study imply that (1) apart from Y-type excitatory input there are significant excitatory non-Y-inputs to area 18; these inputs at least partially consist of indirect X-type input relayed via area 17; (2) in neurons of area 18 that receive both Y-type and non-Y-type excitatory inputs, the Y-type input has a major influence on strength of the response and velocity sensitivity and a lesser influence on the direction selectivity and size of the discharge fields; and (3) area 18 contains mechanisms determining such receptive-field properties as S- or C-type organization, orientation tuning, and direction selectivity which can be accessed either by the Y input or by non-Y input. PMID- 1633129 TI - A psychophysically motivated model for two-dimensional motion perception. AB - A quantitative model is developed to predict the perceived direction of moving two-dimensional patterns. The model incorporates both a simple motion energy pathway and a "texture boundary motion" pathway that incorporates response squaring before the extraction of motion energy. These pathways correspond to Fourier and non-Fourier motion pathways and are hypothesized to reflect processing in the V1-MT and V1-V2-MT pathway, respectively. A cosine-weighted sum of these pathways followed by competitive feedback inhibition accurately predicts the perceived direction for patterns composed of two cosine gratings at different orientations ("plaids"). The model also predicts direction discrimination, differences between foveal and peripheral viewing, changes in perceived direction with exposure duration, motion masking, and motion transparency. PMID- 1633130 TI - Visual callosal projections in the adult ferret. AB - The laminar and tangential organization of visual callosal projections of areas 17 and 18 were investigated in the adult ferret, using histochemical methods to visualize axonally transported horseradish peroxidase (HRP). Normal adult ferrets were given injections of HRP throughout one visual cortex or had gelfoam soaked in HRP applied to the transected corpus callosum. The ferret callosal cell distribution has a greater tangential extent in area 18 than in area 17. In addition, the radial organization of callosal cells in areas 17 and 18 differs: three times as many infragranular cells are present in area 18 than in area 17, although the number of supragranular cells is similar for both areas 17 and 18. Since the projections of alpha retinal ganglion cells are reported to be exclusively contralateral in the ferret (Vitek et al., 1985), callosal projections may make a major contribution to the binocularity of neurons in area 18. PMID- 1633131 TI - A model of the perception of area. AB - A psychophysical experiment was performed to measure the ability of human observers to compare the areas of two geometrical figures (squares and rectangles). The results show a systematic overestimation of rectangle area with respect to that of the squares. A formal model of area perception and its consequent estimation is proposed, which is based on the concept of an 'image function'. It assumes that not the original figure but some specific isocline defined on the image function surface determines area perception. The systematic error observed in the experiment is explained by the model. We discuss the role of different definitions of the image function as well as its parameters on the model performance. PMID- 1633132 TI - Sequential mapping of weighting functions for visual location. AB - The effect upon perceived location of adding an extra dot offset from the centre of a cluster of pseudorandom dots was investigated using a vernier acuity task. With this technique, weighting functions showing the extent to which the added dot pulls the apparent location of the entire cluster can be defined as a function of distance from the centre of the cluster. When dot density within the cluster is high, the weighting functions approximate to what would be expected on the basis of centroid alignment. With low dot densities, it appears that performance is determined by aligning the outermost dots within each cluster. The peak amplitudes of these weighting functions are proportional to the square root of dot density within the clusters. The results are consistent with the view that each vernier element is localised in an orthoaxial direction prior to discrimination of the vernier offset. PMID- 1633133 TI - Are direction and speed coded independently by the visual system? Evidence from visual search. AB - Three visual search experiments examined whether motion is coded as two separate features, speed and direction. Increasing the heterogeneity of the directions in which stimuli moved disrupted detection of a target defined by speed (fast among medium and slow nontargets), suggesting that speed is coded integrally with direction. However, heterogeneity in speed did not disrupt detection of a target moving in a particular direction among nontargets with different directions. This suggests that direction is coded independently of speed. The apparent paradox raised by these contrasting conclusions is consistent with neurophysiological and computational models of motion-detection, which suggest that low-levels of the visual system contain direction-detectors insensitive to speed, while speed is coded at higher levels by detectors which are also sensitive to direction. Evidence consistent with the existence of the latter conjunction detectors was obtained in a final experiment which found search for a conjunction of speed and direction to be parallel. PMID- 1633134 TI - Can human texture discrimination be mimicked by a computer model using local Fourier analysis? PMID- 1633135 TI - Spatial code interference on directional responses. AB - The interference from an irrelevant position cue was compared in a reaction-time paradigm using voice and manual responses. The subjects were required to say 'left' or 'right' or to press left or right keys in response to arrow directions, and the arrows were presented at left or right side display positions irrelevant to the task. Display position significantly increased latency when it did not match the response to the relevant direction cue for both spatial (key-press) and non-spatial (voice) responses (73 and 59 ms, respectively). When presented alone, the position cue was processed faster than the direction cue for both manual and verbal responses. Results are discussed in terms of a common abstract mediator for left-right responses between modes and the processing speed difference between the relevant and irrelevant cue. The irrelevant left-right position code may occupy some limited-capacity channel ahead of the left-right code derived from processing the relevant direction cue. PMID- 1633136 TI - The perceived image: efficient modelling of visual inhomogeneity. AB - When we fixate on a certain location in a scene, the image that our visual system provides us with is not like a snapshot of the scene. Because of visual inhomogeneity, the image we perceive is sharp and clean only around the fixation location, and it gradually blurs and loses detail with increasing distance from that location. In this paper, a procedure is presented that allows one to obtain the luminance distribution in the perceived image of a scene. The procedure is based on a stack distribution model of spatial visual processing, with parameters obtained experimentally. An application of this procedure is presented which allows an explanation of data on the decrease of visual acuity with eccentricity. The advantages of this procedure for taking visual inhomogeneity into account when seeking explanations for perceptual phenomena are also discussed. PMID- 1633137 TI - Cat keratoplasty wound healing and corneal astigmatism. AB - BACKGROUND: A major contributor to postkeratoplasty astigmatism may be donor/recipient disparity. Deficient or excess cornea at the wound is thought to influence the directions of the steep and flat meridians. Using an established model of penetrating keratoplasty in the cat, this study evaluated the morphometry of histopathologic wound features in the steep and flat meridians. METHODS: Thirteen cats had successful penetrating keratoplasties after intentionally misshapen donor corneas were misaligned in misshapen recipient beds. At 9.50 +/- 0.32 (mean +/- 1 SEM) months after keratoplasty, photokeratography was performed and analyzed, corneas were sectioned along the steep and flat meridians, and four histologic sections were processed. Features of the wounds were measured using a Zeiss Videoplan. The relationships between the morphometry of each feature and every other feature, between the morphometry of each feature and eccentricity, and between the steep and flat section morphometry of each feature were statistically evaluated. RESULTS: Epithelial thickness, area of lamellar alteration, length of Descemet's membrane produced postoperatively, and the depth that preoperative Descemet's membrane was embedded in the stroma were correlated with eccentricity (corneal astigmatism). Stromal thickness and the presence or absence of folded and fragmented Descemet's membrane were not correlated with eccentricity. Wound morphometry at the steep meridians was neither correlated with nor significantly different from wound morphometry at the flat meridians. CONCLUSIONS: Differences between healing at the steep and flat meridians were not likely contributors to astigmatism. Disproportionate availability of tissue in wound regions may have affected healing throughout the entire wound over time. The absence of Bowman's layer in cats restricts application of our results to understanding the etiology of corneal astigmatism after penetrating keratoplasty in humans. PMID- 1633138 TI - Circular keratotomy for the correction of astigmatism. AB - BACKGROUND: Mathematical and physical considerations that are contained in Gauss' law lead to the concept of a circular cut for the correction of corneal astigmatism. METHODS: The method applied is the coupling of the aspheric corneal surface to the spherical obturator of the Guided Trephine System and cutting of 90% of the parenchyma. Nineteen human eyes were treated with this technique, using a double-running suture closure. RESULTS: Results of reduction of astigmatism can regularly be obtained but are of different amounts depending on the origin of astigmatism. Mean preoperative refractive astigmatism was 5.41 diopters and mean postoperative refractive astigmatism was 1.34 D. Six eyes required additional tranverse arcuate keratotomy. CONCLUSIONS: The procedure is effective, but the results are variable. It may be improved by the use of obturators that fit the radius of curvature of the cornea. PMID- 1633139 TI - Photorefractive keratectomy as a second attempt to correct myopia after radial keratotomy. AB - BACKGROUND: Undercorrection after radial keratotomy is not uncommon. To correct the residual refractive error, several techniques are available including photorefractive keratectomy. METHODS: We report five eyes of four patients, which remained undercorrected following radial keratotomy and underwent photorefractive keratectomy with an excimer laser (193 nm) to correct the residual myopia, with a follow up of 6 months to 1 year. RESULTS: The corneal-healing response was similar to that of corneas treated by photorefractive keratectomy alone. No permanent corneal scarring occurred. The average preoperative refraction before photorefractive keratectomy was -2.25 +/- 0.55 diopters; it was close to plano (+0.12 +/- 0.26 D) after 6 months. One eye regressed 0.50 D between 6 months and 1 year. Best-spectacle corrected visual acuity did not change. CONCLUSIONS: Excimer laser photorefractive keratectomy seems to be effective as a second procedure in eyes undercorrected following radial keratotomy. PMID- 1633140 TI - Intraoperative and early postoperative complications in 466 radial keratotomies. AB - We have retrospectively studied the intraoperative and early postoperative complications of 466 radial keratotomies. These complications included: microperforations and macroperforations, incisions into the optical zone, and early bacterial corneal ulcers and endophthalmitis. PMID- 1633141 TI - Quantitative measurement of wound spreading in radial keratotomy. AB - BACKGROUND: Many studies of radial keratotomy have been performed, however quantitative laboratory evaluation of the biomechanics of this procedure is still incomplete. Furthermore, most measurements of strain in the past have utilized strip testing, thus destroying the normal physiological structure and water balance of the cornea. METHODS: We report on a membrane inflation method of wound spreading in intact human corneas using the Baribeau Micronscope. RESULTS: We measured a secant elastic modulus of 7.58 x 10(6) N/m2 between 25 and 100 mm Hg. The spreading of radial keratotomy incisions as a function of intraocular pressure showed a maximum spreading of approximately 50 mu at 25 mm Hg at a radius of 3.50 mm from the optical center. A slight increase in spreading was observed in proceeding from a single to four radial incisions. CONCLUSIONS: Quantitative measurement of wound spreading is an important parameter of radial keratotomy and can provide important information regarding opposing theories of the biomechanics of this operation. PMID- 1633142 TI - A comparison of corneal stromal edema induced from the anterior or the posterior surface. AB - BACKGROUND: Many differences between the anterior and posterior corneal stroma have been reported. The physiological and mechanical properties of the cornea are a summation of these properties across each of the corneal regions. This article investigates corneal stromal swelling that is experimentally induced through each surface. METHODS: Corneal stromal swelling was induced in human and rabbit corneas through either the anterior or posterior surface. The rate of stromal swelling was analyzed with a linear regression model. RESULTS: Swelling in the rabbit stroma was 3.65 x faster when induced through the posterior surface than through the anterior surface (p less than .0001), while the human stroma swelled 13.1 x faster through the posterior surface (p less than .0001). The hydration of the stroma increased during swelling through the posterior surface, but paradoxically decreased during swelling through the anterior surface. CONCLUSIONS: These experiments showed that stromal swelling occurs more rapidly through the posterior corneal surface than through the anterior surface. These results may have implications for the refractive surgeon performing laser ablative procedures on the anterior surface of the cornea. PMID- 1633143 TI - An in-vivo technique for monitoring keratocyte migration following lamellar keratoplasty. AB - BACKGROUND: We have recently developed a method for labeling and following the migration of keratocytes using the fluorescent dye, 4',6-diamidino-2-phenylindole (DAPI), which intercalates specifically into the adenine-thymine base pairs of deoxyribonucleic acid (DNA). METHODS: DAPI was applied to a 2-millimeter area of the corneal stroma, at the edge of the microkeratome wound, prior to placement of the autograft. RESULTS: DAPI-labeled keratocytes were identified by epifluorescence microscopy along the microkeratome wound and in the mid-periphery of the lamellar graft by day 7. In contrast, no DAPI-labeled keratocytes were observed in the graft immediately following surgery, indicating that the DAPI labeled keratocytes observed in the graft at day 7 resulted from keratocyte migration, and not from diffusion of DAPI from the host into the graft. CONCLUSIONS: These investigations suggest that DAPI could be a useful probe for monitoring the migration of keratocytes into corneal grafts following lamellar keratoplasty and other corneal transplant surgical techniques. PMID- 1633144 TI - On the safety of 193-nanometer excimer laser refractive corneal surgery. AB - Current literature on the potential hazards of 193-nanometer excimer laser corneal surgery is reviewed. The healing process of the different layers involved in the procedure is examined. The epithelium regenerates without delay or abnormal adhesion. A certain loss of corneal transparency seems to be only a short-term complication. The phototoxic risk for the endothelium and the lens has not yet been fully investigated. This risk is presently thought to be minimal. Factors such as improper corneal centering could lead to degradation of best corrected visual acuity or to loss of contrast sensitivity. Results of the first clinical trials indicate that vision quality does not appear to be adversely affected. The last section reviews studies designed to investigate the mutagenicity and cytotoxicity of 193-nanometer UV radiation. In vivo experiments could find no evidence of cellular transformation. PMID- 1633145 TI - Subepithelial reticular cicatrization following radial keratotomy in a patient with inactive trachoma. AB - BACKGROUND: Opacification of the clear optical zone following radial keratotomy has not been observed before. METHODS AND RESULTS: The authors noted the appearance of subepithelial dense white reticular cicatrization in the central area following radial keratotomy in a patient with inactive trachoma and clear cornea. The corneal changes resulted in regression of the surgical effect and decrease in visual acuity. A good visual result was obtained by performing homoplastic myopic keratomileusis in situ. Clinical and histopathological findings are presented. CONCLUSIONS: Patients undergoing radial keratotomy should be carefully screened for inactive trachoma which may contribute toward postoperative reticulate opacity of the central cornea. PMID- 1633146 TI - The correction of high myopia. AB - There are welcome signs that the ophthalmic profession is at long last facing up to its responsibilities to those unfortunate enough to suffer from high myopia. At this time, it is my opinion that the safest and most effective option is the use of the ZB5M anterior chamber implant inserted into phakic eyes, the updated technique devised by Baikoff and Domilens. In the long term, the future probably lies with the use of corneal inlays using a high refractive index thermoplastic such as polysulfone. PMID- 1633147 TI - The concept of using a different sized diameter corneal graft and host bed has been used in ophthalmology for many years. PMID- 1633148 TI - Epikeratoplasty in the management of keratoconus with aphakia. PMID- 1633149 TI - Binding of the H-ras p21 GTPase activating protein by the activated epidermal growth factor receptor leads to inhibition of the p21 GTPase activity in vitro. AB - There is strong, albeit indirect, evidence for a mitogenic signal transduction pathway comprising growth factors, growth factor receptors, the GTPase activating protein (p120-GAP), and p21ras. To demonstrate a direct physical association between these proteins in the absence of other cell constituents, their interaction was studied in vitro. Our results obtained with homogeneous protein preparations show that the activated epidermal growth factor (EGF) receptor phosphorylates p120-GAP at one site. Phosphorylated p120-GAP remains firmly bound to the receptor at physiological salt concentration; this leads to product inhibition of the receptor kinase activity as shown by diminished autophosphorylation activity and lack of turnover in p120-GAP phosphorylation. Phosphorylated p120-GAP is as active in stimulating the p21ras.GTPase as unphosphorylated GAP. p120-GAP, however, when bound to the EGF receptor is by a factor of 2 less active in stimulating the p21ras.GTPase than free p120-GAP. This effect might contribute to regulate the steady-state level of p21-GTP. PMID- 1633150 TI - High-pressure 31P NMR study of dipalmitoylphosphatidylcholine bilayers. AB - High-pressure 31P NMR was used for the first time to investigate the effects of pressure on the structure and dynamics of the phosphocholine headgroup in pure 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) multilamellar aqueous dispersions and in DPPC bilayers containing the positively charged form of the local anesthetic tetracaine (TTC). The 31P chemical shift anisotropies, delta sigma, and the 31P spin-lattice relaxation times, T1, were measured as a function of pressure from 1 bar to 5 kbar at 50 degrees C for both pure DPPC and DPPC/TTC bilayers. This pressure range permitted us to explore the rich phase behavior of DPPC from the liquid-crystalline (LC) phase through various gel phases such as gel I (P beta'), gel II (L beta'), gel III, gel IV, gel X, and the interdigitated, Gi, gel phase. For pure DPPC bilayers, pressure had an ordering effect on the phospholipid headgroup within the same phase and induced an interdigitated Gi gel phase which was formed between the gel I (P beta') and gel II (L beta') phases. The 31P spin-lattice relaxation time measurements showed that the main phase transition (LC to gel I) was accompanied by the transition between the fast and slow correlation time regimes. Axially symmetric 31P NMR lineshapes were observed at pressures up to approximately 3 kbar but changed to characteristic axially asymmetric rigid lattice lineshapes at higher pressures (3.1-5.1 kbar).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1633151 TI - Barnase has subsites that give rise to large rate enhancements. AB - Barnase is found to have a series of subsites for binding its substrates that confers large rate enhancements. Ribonucleotide substrates of the type Zp0Gp1Xp2Y have been synthesized, where p is phosphate, X, Y, and Z are nucleosides, and G is guanosine. G occupies the primary specificity site. The most important subsite is for p2, followed by that for Y. There appears to be no subsite for the Z or p0 positions. Occupation of the subsite for p2 gives rise to a 1000-fold increase in kcat/Km, composed of a 100-fold increase in kcat and a 10-fold decrease in Km. The Y subsite gives rise to further 20-fold increase in kcat/Km. Rates approaching diffusion control for kcat/Km are observed. kcat for the dinucleotide monophosphate GpU = 0.55 s-1, and Km = 240 microM; this compares with 53 s-1 and 20 microM for GpUp, and 3.3 x 10(3) s-1 and 17 microM for GpApA (the best substrate tested). Cleavage occurs at the 3'-phosphate of guanosine in all cases. There are differences in base specificity at the two subsites for X and Y downstream of the scissile bond. The binding energies of different substrates have been analyzed using thermodynamic cycles. These show that the contributions of the X and Y sites are nonadditive. PMID- 1633152 TI - Comparison of conformational features of staphylococcal nuclease in ternary complexes with pdTp, pdGp, and nitrophenyl-pdTp. AB - The conformations of wild-type staphylococcal nuclease (SNase) in the ternary complexes with thymidine 3',5'-bisphosphate (pdTp), 2'-deoxyguanine 3',5' bisphosphate (pdGp), and thymidine 3'-phosphate 5'-(p-nitrophenylphosphate) (NpdTp) with Ca2+ were examined by two-dimensional NMR NOESY and ROESY experiments. The results of these experiments indicate that the conformational features of the SNase are quite similar in the three ternary complexes. This suggests that the conformational features of SNase, in these ternary complexes, are not strongly dependent on whether the 5'-phosphate is a mono- or diester. This is in contrast to our prior studies on substitutions of active site charged amino acids which indicated that the conformational features of SNase in the ternary complex are quite sensitive to substitutions for active site charged amino acids (Hibler et al., 1987; Wilde et al., 1988; Pourmotabbed et al., 1990). The similarity of the SNase conformational features in the ternary complexes with pdTp and pdGp indicates that the features of the nucleotide bound at the active site are not strong determinants of the enzyme conformation in the ternary complexes. These conclusions are in general agreement with the results on pdApdT ternary complexes with SNase which suggested that it is the conformational features of the bound nucleic acid which determine the differences in catalysis observed for SNase with different substrates (Weber et al., 1991), more so than the conformational features of the enzyme. PMID- 1633153 TI - Phospholipase A2 engineering. Structural and functional roles of highly conserved active site residues tyrosine-52 and tyrosine-73. AB - Site-directed mutagenesis was used to probe the structural and functional roles of two highly conserved residues, Tyr-52 and Tyr-73, in interfacial catalysis by bovine pancreatic phospholipase A2 (PLA2, overproduced in Escherichia coli). According to crystal structures, the side chains of these two active site residues form H-bonds with the carboxylate of the catalytic residue Asp-99. Replacement of either or both Tyr residues by Phe resulted in only very small changes in catalytic rates, which suggests that the hydrogen bonds are not essential for catalysis by PLA2. Substitution of either Tyr residue by nonaromatic amino acids resulted in substantial decreases in the apparent kcat toward 1,2-dioctanoyl-sn-glycero-3-phosphocholine (DC8PC) micelles and the v(o) (turnover number at maximal substrate concentration, i.e., mole fraction = 1) toward 1,2-dimyristoyl-sn-glycero-3-phosphomethanol (DC14PM) vesicles in scooting mode kinetics [Berg, O. G., Yu, B.-Z., Rogers, J., & Jain, M. K. (1991) Biochemistry 30, 7283-7297]. The Y52V mutant was further analyzed in detail by scooting mode kinetics: the E to E* equilibrium was examined by fluorescence; the dissociation constants of E*S, E*P, and E*I (KS*, KP*, and KI*, respectively) in the presence of Ca2+ were measured by protection of histidine-48 modification and by difference UV spectroscopy; the Michaelis constant KM* was calculated from initial rates of hydrolysis in the absence and presence of competitive inhibitors; and the turnover number under saturating conditions (kcat, which is a theoretical value since the enzyme may not be saturated at the interface) was calculated from the vo and KM* values. The results indicated little perturbation in the interfacial binding step (E to E*) but ca. 10-fold increases in KS*, KP*, KI*, and KM* and a less than 10-fold decrease in kcat. Such changes in the function of Y52V are not due to global conformational changes since the proton NMR properties of Y52V closely resemble those of wild-type PLA2; instead, it is likely to be caused by perturbed enzyme-substrate interactions at the active site. Tyr-73 appears to play an important structural role. The conformational stability of all Tyr-73 mutants decreased by 4-5 kcal/mol relative to that of the wild-type PLA2. The proton NMR properties of Y73A suggested significant conformational changes and substantially increased conformational flexibility. These detailed structural and functional analyses represent a major advancement in the structure-function study of an enzyme involved in interfacial catalysis. PMID- 1633154 TI - Kinetic isotope effect analysis of the reaction catalyzed by Trypanosoma congolense trypanothione reductase. AB - African trypanosomes are devoid of glutathione reductase activity, and instead contain a unique flavoprotein variant, trypanothione reductase, which acts on a cyclic derivative of glutathione, trypanothione. The high degree of sequence similarity between trypanothione reductase and glutathione reductase, as well as the obvious similarity in the reactions catalyzed, led us to investigate the pH dependence of the kinetic parameters, and the isotopic behavior of trypanothione reductase. The pH dependence of the kinetic parameters V, V/K for NADH, and V/K for oxidized trypanothione has been determined for trypanothione reductase from Trypanosoma congolense. Both V/K for NADH and the maximum velocity decrease as single groups exhibiting pK values of 8.87 +/- 0.09 and 9.45 +/- 0.07, respectively, are deprotonated. V/K for oxidized trypanothione, T(S)2, decreases as two groups exhibiting experimentally indistinguishable pK values of 8.74 +/- 0.03 are deprotonated. Variable magnitudes of the primary deuterium kinetic isotope effects on pyridine nucleotide oxidation are observed on V and V/K when different pyridine nucleotide substrates are used, and the magnitude of DV and D(V/K) is independent of the oxidized trypanothione concentration at pH 7.25. Solvent kinetic isotope effects, obtained with 2',3'-cNADPH as the variable substrate, were observed on V only, and plots of V versus mole fraction of D2O (i.e., proton inventory) were linear, and yielded values of 1.3-1.6 for D2OV. Solvent kinetic isotope effects obtained with alternate pyridine nucleotides as substrates were also observed on V, and the magnitude of D2OV decreases for each pyridine nucleotide as its maximal velocity relative to that of NADPH oxidation decreases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1633155 TI - A kinetic investigation of phosphoenolpyruvate carboxylase from Zea mays. AB - The reaction catalyzed by phosphoenolpyruvate carboxylase from Zea mays has been studied kinetically. Results of initial velocity patterns and inhibition studies indicate that phosphoenolpyruvate carboxylase has a random sequential mechanism in which there is a high level of synergism in the binding of substrates. The preferred order of addition of reactants is Mg2+, phosphoenolpyruvate, and bicarbonate. The binding of Mg2+ is at equilibrium. Values for the various kinetic parameters are KiMg = 2.3 +/- 0.4 mM, KPEP = 3.6 +/- 0.6 mM, KiPEP = 0.2 +/- 0.07 mM, and Kbicarbonate = 0.18 +/- 0.04 mM. In addition, double inhibition experiments have been performed to examine the nature of the active site interactions with the putative intermediates, carboxy phosphate and the enolate of pyruvate. Highly synergistic inhibition of phosphoenolpyruvate carboxylase was observed in the presence of oxalate and carbamyl phosphate (alpha = 0.0013). However, an antisynergistic relationship exists between oxalate and phosphonoformate (alpha = 2.75). PMID- 1633156 TI - Hydrolysis of phosphoenolpyruvate catalyzed by phosphoenolpyruvate carboxylase from Zea mays. AB - In addition to the normal carboxylation reaction, phosphoenolpyruvate carboxylase from Zea mays catalyzes a HCO3(-)-dependent hydrolysis of phosphoenolpyruvate to pyruvate and Pi. Two independent methods were used to establish this reaction. First, the formation of pyruvate was coupled to lactate dehydrogenase in assay solutions containing high concentrations of L-glutamate and aspartate aminotransferase. Under these conditions, oxalacetic acid produced in the carboxylation reaction was efficiently transaminated, and decarboxylation to form spurious pyruvate was negligible. Second, sequential reduction of oxalacetate and pyruvate was achieved by initially running the reaction in the presence of malate dehydrogenase with NADH in excess over phosphoenolpyruvate. After the reaction was complete, lactate dehydrogenase was added, thus giving a measure of pyruvate concentration. At pH 8.0 in the presence of Mg2+, the rate of phosphoenolpyruvate hydrolysis was 3-7% of the total reaction rate. The hydrolysis reaction catalyzed by phosphoenolpyruvate carboxylase was strongly metal dependent, with rates decreasing in the order Ni2+ greater than Co2+ greater than Mn2+ greater than Mg2+ greater than Ca2+. These results suggest that the active site metal ion binds to the enolate oxygen, thus stabilizing the proposed enolate intermediate. The more stable the enolate, the less reactive it is toward carboxylation and the greater the opportunity for hydrolysis. PMID- 1633157 TI - Mechanistic studies of phosphoenolpyruvate carboxylase from Zea mays with (Z)- and (E)-3-fluorophosphoenolpyruvate as substrates. AB - The catalytic mechanism of phosphoenolpyruvate (PEP) carboxylase from Zea mays has been studied using (Z)- and (E)-3-fluorophosphoenolpyruvate (F-PEP) as substrates. Both (Z)- and (E)-F-PEP partition between carboxylation to produce 3 fluorooxalacetate and hydrolysis to produce 3-fluoropyruvate. Carboxylation accounts for 3% of the reaction observed with (Z)-F-PEP, resulting in the formation of (R)-3-fluorooxalacetate, and for 86% of the reaction of (E)-F-PEP forming (S)-3-fluorooxalacetate. Carboxylation of F-PEP occurs on the 2-re face, which corresponds to the 2-si face of PEP. The partitioning of F-PEP between carboxylation and hydrolysis is insensitive to pH but varies with metal ion. Use of 18O-labeled bicarbonate produces phosphate that is multiply labeled with 18O; in addition, 18O is also incorporated into residual (Z)- and (E)-F-PEP. The 13(V/K) isotope effect on the carboxylation of F-PEP catalyzed by PEP carboxylase at pH 8.0, 25 degrees C, is 1.049 +/- 0.003 for (Z)-F-PEP and 1.009 +/- 0.006 for (E)-F-PEP. These results are consistent with a mechanism in which carboxylation of PEP occurs via attack of the enolate of pyruvate on CO2 rather than carboxy phosphate. In this mechanism phosphorylation of bicarbonate to give carboxy phosphate and decarboxylation of the latter are reversible steps. An irreversible step, however, precedes partitioning between carboxylation to give oxalacetate and release of CO2, which results in hydrolysis of PEP. PMID- 1633159 TI - Bis-ANS as a specific inhibitor for microtubule-associated protein induced assembly of tubulin. AB - 5,5'-Bis[8-(phenylamino)-1-naphthalenesulfonate] (bis-ANS), the fluorescent probe which binds to tubulin, inhibits its assembly into microtubules [Horowitz et al. (1984) J. Biol. Chem. 259, 14647-14650]. The results described in this paper demonstrate that bis-ANS is quite distinct from other well-known microtubule inhibitors in its specificity of action. The inhibitory potentials of bis-ANS and its three structural analogues ANS, Prodan [6-propionyl-2 (dimethylamino)naphthalene], and NSA (naphthalenesulfonic acid) have been compared. It is found that they can be arranged in the following order according to their polymerization inhibitory potentials: bis-ANS approximately equal to Prodan much greater than ANS greater than NSA. Interestingly, the naphthalene nucleus is sufficient to cause inhibition of polymerization. Detailed experiments were carried out to examine the mode of assembly inhibition by aminonaphthalenes at the molecular level, using bis-ANS as a representative. It was found that there was little or no effect of bis-ANS on the assembly of tubulin when polymerization was induced by assembly promoters like taxol, DMSO, or glutamate, or on the assembly of subtilisin-digested protein (tubulin S), for all of which half-maximal inhibition could not be achieved even at 120 microM bis-ANS. On the contrary, bis-ANS acts as an inhibitor in the case of MAP- (MAP2 and tau) and poly(L-lysine)-induced assembly of tubulin, with half-maximal inhibitory concentrations ranging from 1.5 to 7.6 microM. Our results place bis-ANS as a novel inhibitor, which seems to specifically inhibit C-termini-mediated assembly. Of all assembly inhibitors known so far, none exhibits such selection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1633158 TI - Nucleic acid interactive properties of a peptide corresponding to the N-terminal zinc finger domain of HIV-1 nucleocapsid protein. AB - An 18-residue peptide (NC-F1) with an amino acid sequence corresponding to the N terminal zinc finger of human immunodeficiency virus-1 nucleocapsid protein has been shown to bind to nucleic acids by fluorescence and NMR methods. Previously, this peptide has been shown to fold into a defined structure when bound to zinc (Summers et al., 1990). We have used a fluorescent polynucleotide, poly(ethenoadenylic acid), to monitor binding of this peptide to nucleic acids. In the presence of zinc, the peptide had a smaller site size (1.75 nucleotide residues/peptide) than in the absence of the metal ion (2.75). The salt sensitivity of the interaction indicated that two ion pairs are involved in the association of Zn2+ (NC-F1) with polynucleotide, whereas one ion pair is found in the metal-free peptide-nucleic acid complex. Competition experiments with single stranded DNA (ss DNA) in either the presence or absence of Zn2+ showed that the peptide bound to ss DNA. Using NMR methods, we monitored the binding of a synthetic oligonucleotide, d(TTTGGTTT), to Zn(NC-F1). The hydrophobic residues F2 and I10, which are on the surface of the peptide and have been implicated in viral RNA recognition, were shown to interact with the oligomer. In accord with this observation, analysis of the salt dependence of the polynucleotide-peptide interaction indicates a nonelectrostatic component of about -6 kcal/mol, a value consistent with theoretical estimates of stacking energies of phenylalanine with nucleic acid bases. PMID- 1633160 TI - Structural comparison of apomyoglobin and metaquomyoglobin: pH titration of histidines by NMR spectroscopy. AB - Proton NMR spectroscopy was applied to myoglobin in the ferric, water-liganded form (metMbH2O) and the apo form (apoMb) to probe the structure and stability of the latter. Proteins from sperm whale and horse skeletal muscles were studied to simplify the spectral assignment task. Nuclear Overhauser effects and the response of chemical shifts to variations of pH were used as indicators of residual native holoprotein structure in the apoprotein. The investigation was focused in the histidine side chains and their environment. In metMbH2O, the resonances of all imidazole rings not interacting with the heme were assigned by applying standard two-dimensional methods. These assignments were found to differ from those reported elsewhere [Carver, J. A., & Bradbury, J. H. (1984) Biochemistry 23, 4890-4905] except for His-12, -113, and -116. Only one histidine (His-36) has a pK(a) higher than 7, two (His-48 and His-113) have a pK(a) lower than 5.5, and two (His-24 and His-82) appear not to titrate between pH 5.5 and pH 10. In the apoproteins, the signals of His-113 and His-116, as well as those of His-24, -36, -48, and -119 previously assigned in the horse globin [Cocco, M. J.. & Lecomte, J. T. J. (1990) Biochemistry 29, 11067-11072], could be followed between pH 5 and pH 10. A comparison to the holoprotein data indicated that heme removal has limited effect on the pK(a) and the surroundings of these residues. Five additional histidines which occur in the two helices and connecting loops forming the heme binding site were identified in the horse apoprotein. Four of these were found to have pK(a) values lower than that expected of an exposed residue. The NOE and titration data were proposed to reflect the fact that several holoprotein structural elements, in particular outside the heme binding site, are maintained in the apoprotein. In the heme binding region of the apoprotein structure, the low pK(a)'s suggest local environments which are resistant to protonation. PMID- 1633161 TI - Stimulation of the type III olfactory adenylyl cyclase by calcium and calmodulin. AB - Characterization of adenylyl cyclases has been facilitated by the isolation of cDNA clones for distinct adenylyl cyclases including the type I and type III enzymes. Expression of type I adenylyl cyclase activity in animal cells has established that this enzyme is stimulated by calmodulin and Ca2+. Type III adenylyl cyclase is enriched in olfactory neurons and is regulated by stimulatory G proteins. The sensitivity of the type III adenylyl cyclase to Ca2+ and calmodulin has not been reported. In this study, type III adenylyl cyclase was expressed in human kidney 293 cells to determine if the enzyme is stimulated by Ca2+ and calmodulin. The type III enzyme was not stimulated by Ca2+ and calmodulin in the absence of other effectors. It was, however, stimulated by Ca2+ through calmodulin when the enzyme was concomitantly activated by either GppNHp or forskolin. The concentrations of free Ca2+ for half-maximal stimulation of type I and type III adenylyl cyclases were 0.05 and 5.0 microM Ca2+, respectively. These data suggest that the type III adenylyl cyclase is stimulated by Ca2+ when the enzyme is activated by G-protein-coupled receptors and that increases in free Ca2+ accompanying receptor activation may amplify the primary cyclic AMP signal. PMID- 1633162 TI - Characterization of the specific antigenicity of Mycobacterium fortuitum. AB - Mycobacterium fortuitum, biovar, fortuitum, the cause of serious skin and soft tissue infections, can be differentiated from M. fortuitum, biovar. peregrinum, and other rapidly growing opportunistic mycobacteria by the presence of a unique antigenic glycolipid. The glycolipid is among the simplest of the acyl-trehalose containing lipooligosaccharide class. The application of 1H and 13C NMR, methylation analysis, FAB/MS, and other procedures demonstrated the structure, beta-D-Glcp-(1----6)-2-O-acyl-alpha-D-Glcp-(1 in equilibrium with 1)-3,4,6-tri-O acyl-alpha-D-Glcp. Thus, practically all environmental mycobacteria, many of them opportunistic pathogens, can be differentiated serologically and chemically on the basis of unique sugar arrangements within a few classes of glycolipids. The simplicity of the structure in M. fortuitum fortuitum combined with the distinct roughness of the parent strain raises the intriguing possibility that it is a spontaneous rough variant of the other mycobacteria with more elaborate glycolipids. PMID- 1633163 TI - The three-dimensional structure in solution (pH 5.8) of a DNA 9-mer duplex containing 1,N2-propanodeoxyguanosine opposite deoxyadenosine. Restrained molecular dynamics and NOE-based refinement calculations. AB - The solution structure of the complementary d(C1-A2-T3-G4-X5-G6-T7-A8-C9).d(G10 T11-A12-C13-A14-C15-A 16-T17-G18) nonanucleotide duplex (designated X.A 9-mer) that contains a 1,N2-propanodeoxyguanosine exocyclic adduct, X5, opposite deoxyadenosine A14 in the center of the helix at pH 5.8 is investigated by use of restrained molecular dynamics followed by NOE-based back-calculation refinement. The molecular dynamics calculation is based on 91 interresidue and 97 intraresidue interproton distance restraints derived from two-dimensional nuclear Overhauser enhancement data on the X.A 9-mer at mixing times of 50 and 250 ms [Kouchakdjian, M., Marinelli, E., Gao, X., Johnson, F., Grollman, A., & Patel, D.J. (1989) Biochemistry 28, 5647-5657]. Separate runs start from classical A and B DNA and converge to essentially identical structures (atomic root mean square difference of 0.69 A). Both structures are B-type DNA in character and satisfy the experimental distance restraints with the rms difference of only 0.001 A between the calculated and experimental interproton distances. The dynamics behavior of the A----B DNA transition is monitored and analyzed. Our results clearly indicate that the driving force of the convergence is the experimental interproton distance restraints. The molecular dynamics structures are further refined by a back-calculation dynamics which directly minimizes the difference between the observed 2D NOE intensities and those calculated by the full relaxation matrix approach. The fit of the refined structures to the NOE intensities is measured by the NOE R value, which is analogous to the crystallographic residual index. These R values of the final structures are only 0.17. The refined structures are generally B type, and their convergency improves slightly to an atomic root mean square difference of 0.64 A, despite relatively large structural shifts (approximately 1 A) which occur during the back calculation refinement in both cases. These results suggest that the converged refined structures represent reasonable approximations of the solution structure. PMID- 1633164 TI - Secondary structure of streptokinase in aqueous solution: a Fourier transform infrared spectroscopic study. AB - The secondary structure of streptokinase (Sk) in aqueous solution was quantitatively examined by using Fourier transform infrared (FT-IR) spectroscopy. Resolution enhancement techniques, including Fourier deconvolution and derivative spectroscopy, were combined with band curve-fitting procedures to quantitate the spectral information from the amide I bands. Nine component bands were found under the broad, nearly featureless amide I bands which reflect the presence of various substructures. The relative areas of these component bands indicate an amount of beta-sheet between 30 and 37% and an alpha-helix content of only 12-13% in Sk. Further conformational substructures are assigned to turns (25-26%) and to "random" structures (15-16%). Additionally, the correlation of a pronounced component band near 1640 cm-1 (10-16% fractional area) with the possible presence of 3(10)-helices is discussed. PMID- 1633165 TI - Penetration of analogues of H2O and CO2 in proteins studied by room temperature phosphorescence of tryptophan. AB - The influence of the protein matrix on the reactivity of external molecules with a species buried within the protein interior is considered in two general ways: (1) there may be structural fluctuations that allow for the diffusive penetration of the small molecules and/or (2) the external molecule may react over a distance. As a means to study the protein matrix, a reactive species within the protein can be formed by exciting tryptophan to the triplet state, and then the reaction of the triplet-state molecule with an external molecule can be monitored by a decrease in phosphorescence. In this work, the quenching ability (i.e., reactivity) was examined for H2S, CS2, and NO2- acting on tryptophan phosphorescence in parvalbumin, azurin, horse liver alcohol dehydrogenase, and alkaline phosphatase. A comparison of charged versus uncharged quenchers (H2S vs SH- and CS2 vs NO2-) reveals that the uncharged molecules are much more effective than charged species in quenching the phosphorescence of fully buried tryptophan, whereas the quenching for exposed tryptophan is relatively independent of the charge of the quencher. This is consistent with the view that uncharged triatomic molecules can penetrate the protein matrix to some extent. The energies of activation of the quenching reaction are low for the charged quenchers and higher for the uncharged CS2. A model is presented in which the quenchability of a buried tryptophan is inversely related to the distance from the surface when diffusion through the protein is the rate-limiting step.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1633166 TI - Construction and characterization of a spectral probe mutant of troponin C: application to analyses of mutants with increased Ca2+ affinity. AB - A spectral probe mutant (F29W) of chicken skeletal muscle troponin C (TnC) has been prepared in which Phe-29 has been substituted by Trp. Residue 29 is at the COOH-terminal end of the A helix immediately adjacent to the Ca2+ binding loop of site I (residues 30-41) of the regulatory N domain. Since this protein is naturally devoid of Tyr and Trp, spectral features can be assigned unambiguously to the single Trp. The fluorescent quantum yield at 336 nm is increased almost 3 fold in going from the Ca(2+)-free state to the 4Ca2+ state with no change in the wavelength of maximum emission. Comparisons of the Ca2+ titration curves of the change in far-UV CD and fluorescence emission indicated that the latter was associated only with the binding of 2Ca2+ to the regulatory sites I and II. No change in fluorescence was detected by titration with Mg2+. The Ca(2+)-induced transitions of both the N and C domains were highly cooperative. Addition of Ca2+ also produced a red shift in the UV absorbance spectrum and a reduction in positive ellipticity as monitored by near-UV CD measurements. The fluorescent properties of F29W were applied to an investigation of five double mutants: F29W/V45T, F29W/M46Q, F29W/M48A, F29W/L49T, and F29W/M82Q. Ca2+ titration of their fluorescent emissions indicated in each case an increased Ca2+ affinity of their N domains. The magnitude of these changes and the decreased cooperativity observed between Ca2+ binding sites I and II for some of the mutants are discussed in terms of the environment of the mutated residues in the 2Ca2+ and modeled 4Ca2+ states.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1633167 TI - Ionization of amino acid residues involved in the catalytic mechanism of aspartate transcarbamoylase. AB - The chemical and kinetic mechanisms of the reaction catalyzed by the catalytic trimer of aspartate transcarbamoylase have been examined. The variation of the kinetic parameters with pH indicated that at least four ionizing amino acid residues are involved in substrate binding and catalysis. The pH dependence of K(ia) for carbamoyl phosphate and the K(i) for N-(phosphonoacetyl)-L- aspartate revealed that a protonated residue with a pK value of 9.0 is required for the binding of carbamoyl phosphate. However, the variation with pH of K(i) for succinate, a competitive inhibitor of aspartate, and for cysteine sulfinate, a slow substrate, showed that a single residue with a pK value of 7.3 must be protonated for binding these analogues and, by inference, aspartate. The profile of log V against pH displayed a decrease in reaction rate at low and high pH, suggesting that two groups associated with the Michaelis complex, a deprotonated residue with a pK value of 7.2 and a protonated group with a pK value of 9.5, are involved in catalysis. By contrast, the catalytically productive form of the enzyme-carbamoyl phosphate complex, as illustrated in the bell-shaped pH dependence of log (V/K)(asp), is one in which a residue with a pK value of 7.0 must be protonated while a group with a pK value of 9.1 is deprotonated. This interpretation is supported by the results from the temperature dependence of the V and V/K profiles and from the pH dependence of pK(i) for the aspartate analogues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1633168 TI - 13C isotope effects as a probe of the kinetic mechanism and allosteric properties of Escherichia coli aspartate transcarbamylase. AB - 13C kinetic isotope effects have been measured in carbamyl phosphate for the reaction catalyzed by aspartate transcarbamylase. For the holoenzyme, the value was 1.0217 at zero aspartate, but unity at infinite aspartate, with 4.8 mM aspartate eliminating half of the isotope effect. This pattern proves an ordered kinetic mechanism, with carbamyl phosphate adding before aspartate. The same parameters were observed in the presence of ATP or CTP, showing that there is only one form of active enzyme present, regardless of the presence or absence of allosteric modifiers. These data support the Monod model of allosteric behavior in which the equilibrium between fully active and inactive enzyme is perturbed by selective binding interactions of substrates and modifiers, and there are no enzyme forms having partial activity. Isolated catalytic subunits of the enzyme showed similar 13C isotope effects (1.0240 at zero aspartate, 1.0039 at infinite aspartate, 3.8 mM aspartate causing half of the change from one value to the other), but the finite isotope effect at infinite aspartate shows that the kinetic mechanism is now partly random. With the very slow and poorly bound aspartate analog cysteine sulfinate, the 13C isotope effects were 1.039 for both holoenzyme and catalytic subunits and were not decreased significantly by high levels of cysteine sulfinate. The value of 1.039 is probably close to the intrinsic isotope effect on the chemical reaction, while the kinetic mechanism with this substrate is now fully random because the chemistry is so much slower than release of either reactant from the enzyme. PMID- 1633169 TI - 13C and 15N isotope effects as a probe of the chemical mechanism of Escherichia coli aspartate transcarbamylase. AB - 13C and 15N isotope effects have been measured for the aspartate transcarbamylase (ATCase) reaction in an effort to elucidate the chemical mechanism of this highly regulated enzyme. The observed 15(V/K(asp))H2O value for the ATCase holoenzyme at saturing carbamyl phosphate and 12 mM L-aspartate is 1.0045 at pH 7.5, and this value remains unchanged in the presence of 5 mM ATP (activator) or 5 mM CTP (inhibitor). The fact that the isotope effect is not changed by the allosteric modifiers supports the conclusion that the kinetic properties of the active form of ATCase are not influenced by ATP or CTP. The observed 15(V/K(asp)) values for the catalytic subunit of ATCase are also the same as those determined for the holoenzyme, suggesting that the chemical mechanisms of both enzyme species are the same. Quantitative analysis of 13C and 15N isotope effects in both H2O and D2O has led to the proposal of a chemical model for the ATCase reaction which involves a precatalytic conformational change to form an activated complex that facilitates deprotonation of L-aspartate by an enzyme functional group. Nucleophilic attack on the carbonyl carbon of carbamyl phosphate by the alpha amino group of L-aspartate results in the formation of a tetrahedral intermediate. An intramolecular proton transfer leads to formation of products N carbamyl-L-aspartate and inorganic phosphate. PMID- 1633170 TI - Steady-state kinetics and isotope effects on the mutant catalytic trimer of aspartate transcarbamoylase containing the replacement of histidine 134 by alanine. AB - A detailed kinetic analysis of the catalytic trimer of aspartate transcarbamoylase containing the active site substitution H134A was performed to investigate the role of His 134 in the catalytic mechanism. Replacement of histidine by alanine resulted in decreases in the affinities for the two substrates, carbamoyl phosphate and aspartate, and the inhibitor succinate, by factors of 50, 10, and 6, respectively, and yielded a maximum velocity that was 5% that of the wild-type enzyme. However, the pK values determined from the pH dependence of the kinetic parameters, log V and log (V/K) for aspartate, the pK(i) for succinate, and the pK(ia) for carbamoyl phosphate, were similar for both the mutant and the wild-type enzymes, indicating that the protonated form of His 134 does not participate in binding and catalysis between pH 6.2 and 9.2. 13C and 15N isotope effects were studied to determine which steps in the catalytic mechanism were altered by the amino acid substitutions. The 13(V/K) for carbamoyl phosphate exhibited by the catalytic trimer containing alanine at position 134 revealed an isotope effect of 4.1%, probably equal to the intrinsic value and, together with quantitative analysis of the 15N isotope effects, showed that formation of the tetrahedral intermediate is rate-determining for the mutant enzyme. Thus, His 134 plays a role in the chemistry of the reaction in addition to substrate binding. The initial velocity pattern for the reaction catalyzed by the H134A mutant intersected to the left of the vertical axis, negating an equilibrium ordered kinetic mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1633171 TI - The contribution of threonine 55 to catalysis in aspartate transcarbamoylase. AB - Heavy-atom isotope effects and steady-state kinetic parameters were measured for the catalytic trimer of an active site mutant of aspartate transcarbamoylase, T55A, to assess the role of Thr 55 in catalysis. The binding of carbamoyl phosphate to the T55A mutant was decreased by 2 orders of magnitude relative to the wild-type enzyme whereas the affinities for aspartate and succinate were not markedly altered. This indicates that Thr 55 plays a significant role in the binding of CbmP. If, as had been suggested previously, Thr 55 assists in the polarization of the carbonyl group of CbmP, the carbon isotope effect for the T55A mutant should increase relative to that observed for the wild-type enzyme. However, the opposite is seen, indicating that Thr 55 is not involved in stabilizing the oxyanion in the transition state. Quantitative analysis of a series of 13C and 15N isotope effects suggested that the rate-determining step in the reaction catalyzed by T55A trimer may be a conformational change in the protein subsequent to formation of the Michaelis complex. Thus, Thr 55 may facilitate a conformational change in the enzyme that is a prerequisite for catalysis. An altered active site environment in the binary and Michaelis complexes with T55A trimer is reflected in the pH profiles for log V, log (V/K)asp, and pK(i) succinate, show a displacement in the pK values of ionizing residues involved in aspartate binding and catalysis relative to the wild-type enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1633172 TI - 13C isotope effect studies of Escherichia coli aspartate transcarbamylase in the presence of the bisubstrate analog N-(phosphonoacetyl)-L-aspartate. AB - 13C isotope effects have been measured for the aspartate transcarbamylase holoenzyme (ATCase) and catalytic subunit catalyzed reactions in the presence of the bisubstrate analog N-(phosphonoacetyl)-L-aspartate (PALA). For holoenzyme catalyzed reactions in the physiological direction with very low levels of L aspartate as substrate, or with L-cysteine sulfinate as substrate, or in the reverse direction with carbamyl-L-aspartate and phosphate as substrates, the isotope effect data show a slight dependence on PALA concentration. Under these conditions, PALA first stimulates the rate and then inhibits it at higher concentrations. The observed isotope effect at maximum stimulation by PALA is slightly smaller than in the absence of the analog, but as the PALA concentration is increased to reduce the rate to its original value, the observed isotope effect also increases and approaches the value of the isotope effect determined in the absence of PALA. These data suggest that the kinetic properties of the active enzyme are affected by the number of active sites occupied by PALA, indicating communication between subunits, and a mathematical model is proposed which explains our experimental observations. In contrast to these results with the holoenzyme, isotope effects measured for the reaction catalyzed by the isolated catalytic subunits are not altered in the presence of PALA. Taken together, these data are consistent with the two-state model for the homotropic regulation of ATCase. PMID- 1633173 TI - Differential scanning calorimetric study of the thermal unfolding of beta lactamase I from Bacillus cereus. AB - The irreversible thermal unfolding of the class A beta-lactamase I from Bacillus cereus has been investigated at pH 7.0, using differential scanning calorimetry (DSC) and inactivation kinetic techniques. DSC transitions showed a single peak with a denaturation enthalpy of 646 kJ.mol-1 and were moderately scan rate dependent, suggesting that the process was partially kinetically controlled. The inactivation kinetics at constant temperature showed that the irreversible denaturation of the enzyme occurs as the sum of two exponential terms whose amplitudes are strongly temperature dependent within the transition range so that, at the lowest temperatures within this interval, irreversible inactivation would proceed mainly through the slow phase. The fraction of irreversibly denatured enzyme (D) as a function of temperature for a given scanning rate was calculated by numerical integration of the kinetic equation with temperature, using previously determined kinetic parameters. This D form was the most populated of the unfolded states only at temperatures well above the maximum in the calorimetric transition. Combination of the results of kinetic and DSC experiments has allowed us to separate the contribution of the final D state to the excess enthalpy change from the contribution arising from the reversibly denatured forms of the enzyme (I(i), i = 1,..., n), with the resulting conclusion that the scan rate dependence of the calorimetric traces was the result of two different dynamic effects, viz., the irreversible step and a slow relaxation process during formation of the reversibly denatured intermediate states. Finally, the problems of using results obtained at a single scan rate to validate the two-state kinetic model are commented on. PMID- 1633174 TI - Characterization of the copper- and silver-thiolate clusters in N-terminal fragments of the yeast ACE1 transcription factor capable of binding to its specific DNA recognition sequence. AB - N-terminal fragments of ACE1 protein spanning residues 1-122 or 1-110, termed ACE1(122*) and ACE1(110*), respectively, were investigated in regard to their metal- and double-stranded DNA-binding properties. Band mobility shift assays showed that binding to a specific oligonucleotide (termed UASc), containing two ACE1(122*) binding sites, requires the presence of Cu(I) or Ag(I) but does not occur in the presence of divalent metal ions. Both the Ag(I) and the Cu(I) forms of ACE1(122*) were characterized spectroscopically. The Tyr and metal cluster luminescence emission of Cu-ACE1(122*) was specifically quenched by the oligonucleotide UAScL, but not by an oligonucleotide of the same length and base composition but scrambled sequence. The room-temperature luminescence of Cu(I) ACE1(122*) was assigned to a phosphorescence emission, on the basis of its long lived luminescence of approximately 3.5 microseconds. We report the first observation of a Ag(I) metal cluster in solution for Ag(I)-ACE1(122*), which was found to exhibit a quantum yield and average luminescence lifetime that are ca. 6% of that of Cu(I)-ACE1(122*). The three-dimensional structure brought about by the binding of either metal ion appears to be very similar, since dynamic tyrosine fluorescence lifetime measurements, as well as circular dichroism spectra, were nearly identical for Cu- and Ag-ACE1(122*). Based on these results, we present a hypothetical model for the structure of the metal cluster in this class of proteins. PMID- 1633175 TI - Near-infrared Yb(3+) vibronic sideband spectroscopy: application to Ca(2+) binding proteins. AB - We have used near-infrared (NIR) vibronic fluorescence spectroscopy to study the vibrational structure of ligands associated with model complexes of the lanthanide Yb(3+). This technique exploits the similar binding properties of the lanthanide Yb(3+) to probe Ca(2+)-binding sites in proteins. The (NIR) fluorescence of complexed Yb(3+) exhibits, in addition to main 0-0 (2F5/2--- 2F7/2) electronic transition of Yb(3+), weak vibronic sidebands which provide infrared-like, local vibrational spectra of the chelates (inner sphere ligands) of Yb(3+). A similar approach has been used for the lanthanide Gd(3+) (MacGregor, R.B., Jr (1989) Arch. Biochem. Biophys. 274, 312-316) which fluoresces in the UV and which is usually complicated by amino-acid residues fluorescing in the same spectral region. In this same spectral region, other complications in studying photosynthetic membranes occur in the form of the excitation wavelength being actinic, promoting photodegradation of the membranes, as well as the reabsorption of Gd(3+) fluorescence. NIR excitation and fluorescence detection of Yb(3+) avoid these problems when studying photosynthetic membranes. A preliminary study has been conducted here on rat muscle parvalbumin. PMID- 1633176 TI - Uncoupling activity and physicochemical properties of derivatives of fluazinam. AB - The physico-chemical properties and uncoupling activity of eight derivatives of N phenyl-2-pyridinamines related to the fungicide fluazinam were analyzed using rat liver mitochondria. The uncoupling activity of these compounds relies on the deprotonable secondary amino group. One of the derivatives tested (B-3) was slightly more efficient than fluazinam. By phase-distribution analysis we could show that the N-phenyl-2-pyridinamines are chemicals with moderate hydrophobicity. Deprotonation of the compound reduces the water/octanol partition coefficient by about one order of magnitude. The pKA value of the deprotonable group is affected equally by electron withdrawing substituents of the phenyl- and the pyridinyl-ring, and could be predicted simply from the sum of the Hammett coefficients. The uncoupling efficiency was not dependent on the hydrophobicity of the compound, but appeared to be governed by the pKA of the deprotonable group. This structure/uncoupling characteristic is different from that of the generally more hydrophobic uncouplers of the salicylanilide-type. The pKA resulting in the most efficient uncoupling was found to lie in the range of the pH of the reaction medium. A model based on a solution complexation mechanism, which describes this behaviour, is presented. We conclude that the N-phenyl-2 pyridinamines uncoupled the mitochondria by a simple protonophoric cycle involving protonation/deprotonation in the bulk phase, and that the kinetics of uncoupling were primarily governed by the total concentration of the limiting uncoupler species. PMID- 1633177 TI - Ferredoxin and flavodoxin from the cyanobacterium Synechocystis sp PCC 6803. AB - The unicellular cyanobacterium Synechocystis sp PCC 6803 is capable of synthesizing two different Photosystem-I electron acceptors, ferredoxin and flavodoxin. Under normal growth conditions a [2Fe-2S] ferredoxin was recovered and purified to homogeneity. The complete amino-acid sequence of this protein was established. The isoelectric point (pI = 3.48), midpoint redox potential (Em = 0.412 V) and stability under denaturing conditions were also determined. This ferredoxin exhibits an unusual electrophoretic behavior, resulting in a very low apparent molecular mass between 2 and 3.5 kDa, even in the presence of high concentrations of urea. However, a molecular mass of 10,232 Da (apo-ferredoxin) is calculated from the sequence. Free thiol assays indicate the presence of a disulfide bridge in this protein. A small amount of ferredoxin was also found in another fraction during the purification procedure. The amino-acid sequence and properties of this minor ferredoxin were similar to those of the major ferredoxin. However, its solubility in ammonium sulfate and its reactivity with antibodies directed against spinach ferredoxin were different. Traces of flavodoxin were also recovered from the same fraction. The amount of flavodoxin was dramatically increased under iron-deficient growth conditions. An acidic isoelectric point was measured (pI = 3.76), close to that of ferredoxin. The midpoint redox potentials of flavodoxin are Em1 = -0.433 V and Em2 = -0.238 V at pH 7.8. Sequence comparison based on the 42 N-terminal amino acids indicates that Synechocystis 6803 flavodoxin most likely belongs to the long-chain class, despite an apparent molecular mass of 15 kDa determined by SDS-PAGE. PMID- 1633178 TI - Electron-transfer self-exchange kinetics of trimethylphosphine horse-heart myoglobin. AB - Electron self-exchange has been measured by an NMR technique for horse-heart myoglobin. The rate is 3.1 x 10(3) M-1 s-1 at 23 degrees in 0.1 M phosphate at pH 6.9. The rate was weakly dependent on ionic strength up to 0.7 M in added KCl (3.9 x 10(3) M-1 s-1). The enthalpy of activation was 12.1 +/- 0.5 kcal mol-1, and the entropy of activation was -1.2 +/- 0.5 cal mol-1 deg-1. Analysis of the data in terms of the Marcus theory gives a reorganization energy, lambda, for self-exchange of 1.6 eV mol-1. PMID- 1633179 TI - Mitochondrial inner membrane permeability changes induced by octadecadienoic acid hydroperoxide. Role of mitochondrial GSH pool. AB - The effect of exogenous octadecadienoic acid hydroperoxide (HPODE) on the functional properties of inner membrane of isolated rat liver mitochondria, as evaluated by the measurement of the membrane potential (delta psi) has been studied. Very low concentrations of HPODE (1.5-4.5 nmol/mg prot.) do not modify the delta psi of control mitochondria appreciably while bringing about the drop of delta psi, in a concentration-dependent mode, in mitochondria with a GSH level diminished by approx. 60%. Mitochondrial GSH depletion was obtained by intraperitoneal administration of buthionine sulfoximine, a specific inhibitor of GSH synthesis, to rats. The presence in the incubation system of GSH-methyl ester which normalizes mitochondrial GSH, fully prevents any drop in levels of delta psi induced by HPODE. The same protective effect has been presented by EGTA, which chelates the available Ca2+. Neither an antioxidant nor a specific inhibitor of mitochondrial phospholipase A2 are able to prevent the HPODE effect. From the results obtained we can assume that HPODE itself, at the concentrations used here, induces permeability changes in the inner membrane, with the loss of coupled functions, when the GSH mitochondrial level is below a critical value. PMID- 1633180 TI - Trails of inquiry and thought leading toward today's bioenergetics. AB - Significant experimental observations and concepts leading from various sources toward today's bioenergetics are briefly sketched. To limit the essay to manageable proportions main consideration is given to origins in research on metabolism and biological oxidations and attendant energy conversions. Relevant data and dates are summarized in table form. PMID- 1633181 TI - The photosystem I-like P840-reaction center of green S-bacteria is a homodimer. AB - An operon encoding the P840 reaction center of Chlorobium limicola f.sp.thiosulfatophilum has been cloned and sequenced. It contains two structural genes coding for proteins of 730 and 232 amino acids. The first protein resembles the large subunits of the Photosystem I (PS I) reaction center. Putative binding elements for the primary donor, P840 in Chlorobium and P700 in PS I and for the acceptors A(o), A(1) and FeS-center X are conserved. The second protein is related to the PS I subunit carrying the FeS-centers A and B. Since all our efforts to find a gene for a second, large subunit failed, the P840 reaction center probably is homodimeric. PMID- 1633182 TI - Structure-function relationships of cytochrome b by the genetic approach: intragenic revertants derived from frameshift mutations in the Saccharomyces cerevisiae apocytochrome b gene. PMID- 1633183 TI - Engineering protein structure for electron transfer function in photosynthetic reaction centers. AB - A basic relationship is defined that incorporates the three parameters that effectively modulate the rate of intraprotein electron transfer, namely distance, free energy and reorganization energy. This empirically validated relationship is used to explore the minimal requirements for protein-catalyzed conversion of excited electronic states into stable charge separated states, the essence of photosynthesis. PMID- 1633184 TI - The energy-transducing NADH-quinone oxidoreductase (NDH-1) of Paracoccus denitrificans. PMID- 1633185 TI - Human mitochondrial complex I dysfunction. AB - In humans, complex I dysfunction has been observed in a high percentage of patients with mitochondrial myopathy. Analysis of mitochondria from these patients suggests the function and assembly of complex I is particularly susceptible to abnormalities of mitochondrial DNA, involving either point mutations of tRNA genes or major deletions. The evidence for a complex I defect in Parkinson's disease is accumulating, although the cause of this deficiency or the role it plays in the events that culminate in dopaminergic cell death remains unresolved. PMID- 1633186 TI - Gene defects in Leber hereditary optic neuroretinopathy. PMID- 1633187 TI - The lactose permease of Escherichia coli: a paradigm for membrane transport proteins. PMID- 1633188 TI - The involvement of cyclosporin A binding proteins in regulating and uncoupling mitochondrial energy transduction. AB - The uncoupling of mitochondrial energy transduction by excess Ca2+ may be a factor in the pathogenesis of tissue injury brought about by energy deprivation, for example, in ischaemia. In isolated mitochondria the lesion appears as a large, 20 A, pore in the inner membrane. The pore is blocked potently by the immunosuppressant cyclosporin A. Cyclosporin A also markedly retards collapse of the mitochondrial inner membrane potential in energy-deprived (respiration inhibited) cardiomyocytes as judged by changes in rhodamine 123 fluorescence, and prolongs cell viability. A potential mitochondrial target for cyclosporin A is the matrix protein cyclophilin. Purified cyclophilin activates the respiratory chain of submitochondrial particles. This might reflect not only a physiological function of this protein, but also a component involved in the generation of the 20 A pore under pathological conditions. PMID- 1633189 TI - Mitochondrial substrate carriers. PMID- 1633190 TI - The energetics of protein import into mitochondria. PMID- 1633191 TI - Purification and electrospray mass spectrometry of aldose reductase from pig lens. AB - Aldose reductase (alditol: NADP+ 1-oxidoreductase, EC 1.1.1.21) has been purified from pig lens to homogeneity by a rapid and efficient three-step procedure involving poly(ethylene glycol) fractionation, ion-exchange chromatography and chromatofocusing. The homogeneity of the purified enzyme was examined by polyacrylamide gel electrophoresis under native and denaturing conditions, by isoelectric focusing and by high-performance liquid chromatography on a size exclusion column. The highly purified enzyme is a monomeric protein with a molecular mass of 35,775 +/- 3 Da as determined by electrospray mass spectrometry (ESMS). This purification procedure is particularly suited for the preparation of triclinic single crystals of pig lens aldose reductase, which are currently used in X-ray studies of this enzyme. PMID- 1633192 TI - Characterisation of a tryptic peptide from human placental ribonuclease inhibitor which inhibits ribonuclease activity. AB - Affinity-purified human placental ribonuclease inhibitor (PRI) was digested by trypsin. Subsequent fractionation of the hydrolysate by HPLC yielded 44 fractions, 3 of which retained the ability to inhibit ribonuclease. One of these, the most active, was a 15 amino acid peptide which had an amino acid composition corresponding to a tryptic fragment of PRI. This peptide was synthesised, and preliminary experiments were carried out on its interactions with ribonuclease. These experiments suggested that the behaviour of the peptide in terms of effect of pH, and effect of salt concentration were similar to the protein from which it was derived. These studies together with the strategic positioning of the peptide in the sequence of the ribonuclease inhibitor, suggest that this segment of PRI has an important role in the inhibitory activity of the intact protein. PMID- 1633193 TI - Close amino acid sequence relationship between the new plasmid-mediated extended spectrum beta-lactamase MEN-1 and chromosomally encoded enzymes of Klebsiella oxytoca. AB - Isolated from an Escherichia coli strain MEN-1 is a plasmid-mediated beta lactamase that confers resistance to methoxy imino third-generation cephalosporins. The protein purified to homogeneity was digested by trypsin, chymotrypsin and endoproteinase Asp-N. Amino acid sequence determinations of the resulting peptides gave rise to the alignment of the 263 residues of the beta lactamase. From amino acid sequence comparison MEN-1 was found to share more than 72% identity with the chromosomally mediated beta-lactamases of Klebsiella oxytoca. Therefore, MEN-1 is the first transferable extended-spectrum beta lactamase which is not directly derived from the widespread TEMs or SHV-1 penicillinases with which it presents less than 39% identity. PMID- 1633194 TI - Hydrogen bond network of cytochrome P-450cam: a network connecting the heme group with helix K. AB - During investigations of the structural character of a mutant P-450cam where Glu 286 is replaced with lysine, we obtained evidence of a hydrogen bond network between helix K and the heme group via helix L of P-450cam. This mutant protein loses the ability to maintain the heme group in a proper position, possibly due to a break in the hydrogen bond network. PMID- 1633195 TI - Inhibition of D-3-aminoisobutyrate-pyruvate aminotransferase by 5-fluorouracil and alpha-fluoro-beta-alanine. AB - Among pyrimidine derivatives, we found that 5-fluorouracil potently inhibited purified rat liver D-3-aminoisobutyrate-pyruvate aminotransferase, whereas 5 fluorouridine did so to a much lesser extent. 5-Fluorouracil acted as a competitive inhibitor against beta-alanine with a Ki of 56 microM, and was uncompetitive against pyruvic acid, with a Ki of 73 microM. alpha-Fluoro-beta alanine, a metabolite of 5-fluorouracil, was also a competitive inhibitor with respect to beta-alanine with a Ki of 8.0 mM. 5-Fluorouracil acted also as a competitive inhibitor of 4-aminobutyrate aminotransferase with respect to beta alanine with a Ki value of 1.9 mM, and was uncompetitive against 2-oxoglutaric acid, with a Ki of 1.8 mM. PMID- 1633196 TI - Characterization of aldehyde reductase of Sporobolomyces salmonicolor. AB - An NADPH-dependent aldehyde reductase (EC 1.1.1.2) isolated from Sporobolomyces salmonicolor AKU 4429 was further characterized. The enzyme also catalyzed the reductions of D-glucuronate, D-glucose, D-xylose and D-galactose at high concentrations. Km values for D-glucuronate and D-glucose are 345 and 4270 mM, respectively. Quercetin, dicoumarol and some SH-reagents inhibited the enzyme activity. NH2-terminal amino acid sequence analysis showed that the S. salmonicolor enzyme is partially the same as the aldo-keto reductase family proteins in primary protein structure. PMID- 1633197 TI - Highly homologous cytochromes P-450 and b5: a model to study protein-protein interactions in a reconstituted monooxygenase system. AB - Cytochrome b5 from mouse and rat liver formed a type I spectral complex with two murine cytochrome P-450 isozymes, the P450Coh and P450PBI. Mouse b5 stimulated the reactions catalyzed by reconstituted P450Coh and an equimolar amount of b5 to P450Coh was needed for maximal effect. In contrast, rat b5 inhibited P450Coh mediated reactions progressively starting from 1:1 ratio of b5 to P-450. Neither b5 had any effect on reactions catalyzed by P45015 alpha, an isozyme highly homologous to P450Coh, but with a point mutation (Arg-129----Ser) at site considered important for P-450-b5 interactions. In case of P450PBI, neither b5 protein had any effect on the associated activities at b5: P-450 ratios below 1, and a progressive inhibition occurred when b5: P-450 ratio was above 1. The results were similar with either rat or mouse liver NADPH-cytochrome P-450 reductase used in reconstitution demonstrating that the critical differences take place in P-450-b5 interactions. Kinetic and spectral experiments revealed that the stimulatory and inhibitory effects of b5 on the enzymatic reactions were due to corresponding changes in the reaction velocity, and that b5 does not compete with the flavoprotein nor with the substrate for binding to P-450. These results indicate that the high spin shift of P-450 does not necessarily correlate with enhanced reaction rates. Also, the increase in the coupling efficiency of P450PBI may result from the increased affinity for substrate in the presence of b5. Sequenation of mouse b5 peptides generated with proteinases revealed three amino acid changes between the mouse and rat b5, two of which appeared at the hydrophobic domain necessary for the P-450-b5 interaction. This could explain the species specificity of b5 proteins in supporting the P-450-mediated reactions. This is the first time functionally important differences in the interaction of highly homologous cytochromes P-450 and b5 have been demonstrated. Isozymes P45015 alpha and P450Coh, and mouse and rat b5 could serve as an excellent model for further studies on the nature and significance of P-450-b5 interactions. PMID- 1633198 TI - Biochemical and physiological studies on two T-kininogen species using monoclonal antibodies. AB - Rat T-kininogens were characterized in plasma, urine and liver slice incubation medium in different physiological conditions using monoclonal antibodies that allow to distinguish between the two forms of T-kininogen. T-kininogen purified from the plasma of both normal and inflamed Wistar and Sprague-Dawley rats was found to contain the two forms of T-kininogen, TI and TII, separated by non denaturing polyacrylamide gel electrophoresis. The two forms were also found in the plasma of several strains of normal and inflamed rats, except in the plasma of the Buffalo rat which contained only TII-kininogen. The two forms of T kininogen were also found in the media in which liver slices from inflamed and non-inflamed wistar rats had been incubated. The urine T-kininogen of normal rats was chiefly TI-kininogen, but both forms were found in the urine of inflamed rats. T-kininogen in the plasma of normal and inflamed rats was further characterized by chromatography on Con A-Ultrogel. In normal plasma, we observed a ratio of non-retained to retained T-kininogen of 0.41. The retained T-kininogen was eluted as two peaks, one eluted with 45 mM and the other with 120 mM alpha methyl-D-glucoside. The ratio of non-adsorbed to adsorbed T-kininogen in inflamed Wistar rat plasma was 1.40 and the retained material was almost exclusively in a single peak, which eluted with 50 mM alpha-methyl-D-glucoside. The non-adsorbed and adsorbed fractions contained both forms of T-kininogen, but the protein bands in the non-retained fraction had greater mobilities on non-denaturing PAGE. SDS PAGE analysis of T-kininogen deglycosylated by N-glycosidase F showed a major band with a molecular mass of 50 kDa, whereas the molecular mass of the native form was 66 kDa. We concluded that both forms of T-kininogen exist in the non inflamed and the inflamed rat plasma, except for the Buffalo rat, and that T kininogen displays a different chromatographic pattern on Con A-Ultrogel after inflammation suggesting altered glycosylation. PMID- 1633199 TI - Overproduction, purification and characterization of SecD and SecF, integral membrane components of the protein translocation machinery of Escherichia coli. AB - SecD and SecF proteins were overproduced by means of recombinant DNA technology. Immunoblot and amino-acid sequencing analysis revealed that the overproduced proteins are SecD and SecF. The SecD- or SecF-overproduced membrane fraction was subjected to differential solubilization. The SecD protein was then purified through ion-exchange and size-exclusion chromatographies. The SecF protein was purified through size exclusion chromatography. Proteoliposomes reconstituted from the purified SecD and SecF together with SecE and SecY were used to analyze the translocation activity. SecD and SecF did not exhibit significant effects on the translocation activity of proteoliposomes. The amounts of SecD and SecF in overproducers were determined densitometrically on a stained SDS gel and their overproduction (fold) was determined by means of immunoblot analysis. Then the number of these molecules in one normal cell were estimated. From these numbers, together with those of other Sec proteins, the number of the translocation machinery existing in one Escherichia coli cell was inferred to be around 500. PMID- 1633200 TI - Purification, characterization and preliminary X-ray study of fumarase from Saccharomyces cerevisiae. AB - Fumarase (fumarate hydratase, EC 4.2.1.2) from Saccharomyces cerevisiae has been purified to homogeneity by a method including acetone fractionation, DEAE ion exchange and dye-sorbent affinity chromatography. The suggested method allows fumarase purification with a yield higher than 60% and may be used to obtain large enzyme quantities. The native protein consists of four subunits with a approximately 50 kDa molecular mass each and has an isoelectric point at pH 6.5 +/- 0.3. The equilibrium constant for fumarate hydration is about 4.3 (25 degrees C, pH 7.5), the Michaelis constants for fumarate and 1-malate are approximately 30 microM and approximately 250 microM, respectively. The enzyme is activated by substrates and multivalent anions, the activation seems to be of a non competitive type. The fumarase complex with meso-tartaric acid has been crystallized by the vapor diffusion method. The unit cell parameters are a = 93.30, b = 94.05 and c = 106.07 A, space group P2(1)2(1)2(1). The unit cell contains 2 protein molecules. The crystals diffract to at least 2.6 A resolution and are suitable for X-ray structure analysis. PMID- 1633201 TI - Unfolding and trypsin inactivation studies reveal a conformation drift of glucose 6-phosphate dehydrogenase upon binding of NADP. AB - Binding of NADP to glucose-6-phosphate dehydrogenase (G6PD) from Dicentrarchus labrax liver has stabilized its native structure against thermal inactivation, guanidine hydrochloride unfolding and inactivation by tryptic digestion. The time course of G6PD inactivation by guanidine hydrochloride in the presence of NADP has provided experimental evidence in favor of a conformational drift upon NADP binding to the bass enzyme. Based on the inactivation patterns obtained when the enzyme was treated with guanidine hydrochloride and trypsin, it is proposed that the enzyme conformation induced upon NADP binding is in slow equilibrium with the conformation stabilized in the absence of NADP. FPLC studies have shown that micromolar concentrations of NADP induced oligomerization of G6PD. In addition, the different K0.5 values of NADP binding to the enzyme, ranging from 1-2 microM (from trypsin inactivation) to 90 microM (from titration of the intrinsic fluorescence), suggest a step-wise binding of NADP to the oligomer, with negative cooperativity in the saturation process. PMID- 1633202 TI - [35 years of organized emergency medicine--what remains to be done?]. PMID- 1633203 TI - [The scientific basis of cardiopulmonary and cerebral resuscitation]. AB - A survey is given on the scientific background of cardiopulmonary-cerebral resuscitation, which supposedly will be the basis of all clinical practice in this field. Haemodynamic, respiratory, acid-base, and cerebral problems are discussed in detail. As for haemodynamics, the pathomechanisms of the conventional "heart pump" and the "thoracic pump" as background of the "New CPR" are compared, the flow being generated by a direct compression of the heart in the former and by a phasic increase of the intrathoracic pressure in the latter case. Combined effects of both modalities mainly depending on the geometry of the thoracic cage, are usually seen. Improvement of flow by modifying the criteria of thorax compression (duration, frequency, strength) is then discussed, and new methods or CPR as e.g. simultaneous/synchronous compression/respiration, Vest CPR, MAST-CPR, abdominal compression and Cough-CPR are mentioned and their mechanisms explained. Finally, open cardiac massage is no doubt superior to all the other indirect and closed methods of cardiac resuscitation. Defibrillators and heart-lung "thumpers" are then described, mentioning the improvements in respect of automatic and semi-automatic defibrillation and the progress made by developing flexible and individually adaptable types of "thumpers". On assessing the sympathicomimetic drugs, it is evident that epinephrine is the method of choice in the acute phase of resuscitation; the pure beta-adrenergics isoprenaline and orciprenaline are not used any more, whereas the alpha-mimetics, although acutely effective similar to epinephrine, cannot produce positive long term effects; the combination of dobutamine and dopamine seems to be ideal for establishing stable haemodynamic situations following a successful acute reanimation procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1633204 TI - [Intravenous thrombolysis in acute myocardial infarct: optimization of the therapeutic strategy by informing the patients and physicians]. AB - Intensive education of patients and physicians helps to increase the incidence of thrombolytic therapy in patients with myocardial infarction. Important factors in this process are: 1. Reduced delays in patients' awareness of the severity of his symptoms, 2. shorter time periods from patients' hospital admission to the initiation of thrombolytic therapy, 3. more indications by educated physicians with a higher degree of precision, and 4. reduced catalogue of contraindications. PMID- 1633205 TI - [Resuscitation of patients using a cardiopulmonary bypass]. AB - The use of cardiopulmonary bypass within the framework of resuscitation justifies hopes for better results after cardiovascular arrest. By restituting sufficient cardiovascular conditions both the global and especially the cerebral blood flow situation are improved, so that, in turn, better neurological results can be expected after cardiopulmonary resuscitation. However, further decisive successes by using the cardiopulmonary bypass can be expected only in connection with new therapeutic concepts of reanimation. PMID- 1633206 TI - [New standards for catecholamine therapy in cardiopulmonary resuscitation? Results of a modified application in a resuscitation model]. AB - Using a standardized porcine CPR-model (3 min of cardiac arrest induced by ventricular fibrillation) the effects of epinephrine (10 micrograms/kg iv, 50 micrograms/kg iv, 100 micrograms/kg endobronchially, eb) and norepinephrine (10 micrograms/kg iv, 100 micrograms/kg eb) on resuscitability and early post resuscitation haemodynamics were compared. Success rate was 100% after epinephrine 10 micrograms/kg iv and 100 micrograms/kg eb, 75% after epinephrine 50 micrograms/kg iv, 80% after norepinephrine iv and 60% after norepinephrine eb. In an unmedicated control group 50% of all animals were successfully resuscitated. Early post-resuscitation haemodynamics in the high dose epinephrine group were characterized by tachycardia and progredient myocardial failure, while in the norepinephrine groups a low cardiac output was accompanied by small cardiac stroke volumes and an increased vascular resistance. It is concluded that iv or eb epinephrine given in standard doses has still to be considered as the drug therapy of choice after short term cardiac arrest or in the presence of ventricular fibrillation. Before different drugs or dosing strategies can be recommended, further experimental and clinical validation is required. PMID- 1633207 TI - [Current aspects of resuscitation. Introduction]. PMID- 1633208 TI - [New developments and standards for mechanical measures in cardiopulmonary resuscitation]. PMID- 1633209 TI - [Buffer therapy in cardiopulmonary resuscitation--indication or routine?]. PMID- 1633210 TI - [Limits of cerebral resuscitation. Pathophysiologic background and therapeutic approaches]. PMID- 1633211 TI - [The effect of first aid (layman) resuscitation on cardiopulmonary resuscitation]. PMID- 1633212 TI - [Suture fixation of a Swan Ganz catheter to the left brachiocephalic vein during re-thoracotomy]. AB - This case report describes the intraoperative fixation of a Swan-Ganz catheter at the left brachiocephalic vein by a suture during rethoracotomy in a cardiac surgical patient. In case of a rethoracotomy by median sternotomy the right-sided veins should be preferred for the insertion of a Swan-Ganz-catheter. Furthermore the free mobility of the catheter should be controlled before closure of the thorax. PMID- 1633213 TI - [Historical vignette (4) "A new apparatus for optical pulse control in anesthesia"]. PMID- 1633214 TI - Control of staphylococcal adhesion to polystyrene surfaces by polymer surface modification with surfactants. AB - The adherence of three clinical isolates of Staphylococcus epidermidis to model polystyrene surfaces was studied in vitro using epifluorescent image analysis. A series of 16 Pluronic surfactants (A-B-A block copolymers where A is poly(ethylene oxide) (PEO) and B is poly(propylene oxide) (PPO)) were used as surface modifiers for the model polystyrene surfaces. Substantial reductions (up to 97%) in bacterial adhesion levels were achieved with all copolymers tested, irrespective of the PPO or PEO block lengths. It appears likely that such treatments create a sterically stabilized surface with adsorbed PEO chains, conferring nonspecific anti-adhesive properties which can limit bacterial attachment. PMID- 1633215 TI - Heparin-poly(ethylene glycol)-poly(vinyl alcohol) hydrogel: preparation and assessment of thrombogenicity. AB - Heparin was immobilized on to poly(vinyl alcohol) hydrogel (PVA) through the free isocyanate end-group on a poly(ethylene glycol) (PEG2000) which had been previously covalently linked to the hydrogel via a urethane moiety. The intention was to reduce the platelet reactivity of the PVA while also suppressing fibrin formation. Elemental nitrogen analysis revealed that the total amount of bound heparin was 19 +/- 7 mumol/g of dried gel. An increase in the in vitro whole blood clotting time of PVA was observed. This was attributed to bound heparin, as the elution rate of heparin from the gel (23 pmol/m2 min) was too low to produce a significant bulk concentration to interfere with fibrin formation. Ex vivo assessment using a chronic canine A-V shunt showed that the bound heparin hydrogel had no effect on the drop in the number of platelets induced by PVA hydrogel, but increased the fractional rate of platelet destruction from approximately 0.35/d to an average value of 0.42/d. PMID- 1633216 TI - Grafting reactions and heparin adsorption of poly(amidoamine)-grafted poly(urethane amide)s. AB - Differently terminated poly(amidoamine) (PAA) oligomers were grafted on the surface of poly(ether urethane amide)s (PEUAm), with fumaric or maleic acid moieties. The grafting reaction was Michael-type addition of amino groups to activated double bonds in the PEUAm backbone. PAAs having primary amino, or secondary amino end-groups were directly grafted on the surface of PEUAm sheets. For vinyl-terminated chains an alpha, omega amino-polyether spacer was introduced initially, following the same addition mechanism. Ungrafted and grafted materials were characterized, besides other analytical techniques, by ATR FT-IR spectroscopy. The heparin adsorption on PEAUm films was analysed after its elution from heparinized samples, quantified by coagulation tests (aPTT), and related to the presence of the PAAs chains grafted on to the surface. Results indicate that PAA-grafted PEUAm elastomeric biomaterials, display enhanced heparin adsorption abilities. PMID- 1633217 TI - Synthesis and physicochemical characterization of a hydrophilic polyurethane able to bind heparin. AB - The synthesis of a new segmented polyurethane containing quaternary ammonium groups in the side-chain is reported. The quaternization was carried out both on the polymer dissolved in an organic solvent and on polymer films. Polymeric films quaternized by both techniques were heparinized. The amount of bonded heparin, determined by spectrophotometry, was remarkably higher than previously described. Polymer quaternized in solution bonded more heparin than that heparinized directly on film. In vitro evaluations of antithrombogenicity by activated partial thromboplastin time (APTT) carried out on the films confirmed these data. The polymers were also characterized by chemical, i.r., n.m.r., differential scanning calorimetry and viscometric techniques. PMID- 1633218 TI - New artificial connective matrix-like structure: thrombogenicity and use as endothelial cell culture support. AB - The recently described artificial connective matrix made of elastin solubilized peptides, type I+III collagens and connective proteins is shown to have structural and biological properties very close to the natural arterial subendothelium: the capacity to promote endothelial cell cultures maintaining their phenotype expression and its non-thrombogenicity. This new bioactive composite material could be used to replace arteries. PMID- 1633219 TI - Degradation of collagen suture in vitro and in vivo. AB - In vitro and in vivo degradation of collagen suture was investigated focussing on the change in the mechanical properties and weight. The in vitro hydrolysis was carried out for catguts using collagenase (pH 7.4) and pepsin (pH 1.6), simulating the in vivo environments. The kinetic study on the weight loss of the fibre at the collagenase hydrolysis suggested that the degradation proceeded gradually from the surface of the fibre into the core. The enzymatic hydrolysis was different from the non-enzymatic acidic hydrolysis which resulted in almost homogeneous degradation throughout the cross-section of the fibre from the beginning of the hydrolysis reaction. The rate of weight loss with enzymatic hydrolysis was in good agreement with that predicted under the assumption of continuous erosion from the surface. When the collagen sutures were implanted in the subdermal tissue of rabbits, severe infiltration of macrophages and neutrophils was observed at 4 wk post-implantation, probably because of the degradation products from the implanted sutures. Comparison of the tensile strength decrease with the weight loss observed at the in vivo degradation revealed that enzymatic and non-enzymatic hydrolysis occurred concurrently in the subcutaneous tissue. PMID- 1633220 TI - Investigation of Ti/Al2O3 joints with intermediate tantalum and niobium layers. AB - The microstructure of TiTa30 alloys diffusion bonded to a 99.7 wt% Al2O3 ceramic was subdivided into a reaction double layer containing the intermetallic phases TiAl and Ti3Al and the (alpha + beta) Ti microstructure. Excellent fracture toughness data of the TiTa30/Al2O3 joints of about 37 J/m2 were obtained after welding at 1200 degrees C for 1 h. The fracture energies of the joints were strongly dependent on the welding temperature which also influenced the thickness of the reaction double layer. The uptake of aluminium and oxygen into the reaction layer and the metal caused an embrittlement and decreased the yield stress and ductility of the metal. Introducing an Nb or Ta layer between pure Ti and Al2O3 before welding resulted in high fracture energies of 40 J/m2 for the Ti/Al2O3 joints. The thermal-induced stresses at the metal-ceramic interface were reduced by the occurrence of an Nb- or Ta-enriched region. The intermediate metal foils also decreased the O and Al uptake of the metal and therefore reduced the brittleness of the reaction zone and the adjacent metal. The thermal-induced stresses at the metal-ceramic interface caused a deflection of the crack into the ceramic during fracture mechanical testing in four-point bending. PMID- 1633221 TI - Solubility and disintegration of zinc phosphate cement. AB - The mechanism of erosion of a zinc phosphate cement was studied using two experimental procedures: discs of dental cement were immersed in distilled water under unrenewed conditions as defined by ISO standard; or discs were immersed under continuously running distilled water to simulate the oral environment. Both experiments revealed no physical disintegration mechanism, and suggest that erosion is only controlled by dissolution. PMID- 1633222 TI - Evaluation of the calcium phosphate ceramic implant by non-invasive techniques. AB - Current routine radiological procedures do not quantify the degree of calcium phosphate ceramic implant integration with the host bone, nor the rate of remodelling processes in the latter. The successful clinical use of non-invasive techniques in assessing bone mass deserves attention from surgeons and scientists dealing with hard tissue prosthetics and implants. Two suitable techniques for such non-invasive sequential analysis of the ceramic implant and host bone are outlined. PMID- 1633223 TI - Determination of three-dimensional morphometry of adherent cells by surface profilometry. AB - A three-dimensional, non-contacting surface profiler was used to analyse cells that had been previously prepared for scanning electron microscopy. The height of ten attached and spread cells was measured in both two- and three-dimensions (2-D and 3-D). The 2-D scan is a typical, linear profilometer output, while a 3-D image is produced with a 3-D detector. The 3-D contour plots of each cell were then compared with scanning electron microscopy micrographs by digitizing four morphological parameters: perimeter, surface area, long axis and short axis of each cell. A paired Student's t test showed that the two imaging techniques are not equivalent. Non-equivalence was attributed to a difference in the method of calibration. However, when combined with scanning electron microscopy, the profiler allowed complete three-dimensional quantitative analysis of cellular morphology. PMID- 1633224 TI - Biodegradable polymers. I. Synthesis of hydrolysis-sensitive poly[(organo)phosphazenes]. AB - Polyphosphazenes with hydrolytic labile substituents have potential as biodegradable materials. By proper choice of the substituents, polymers can be prepared which degrade in vivo to form harmless products. The rate of biodegradation and the nature of the degradation products can be varied by changing the chemical composition of the polymers. A series of new degradable polyphosphazene derivatives are described. The synthesis of phosphazene polymers with various amounts of ethyl 2-(O-glycyl)lactate or ethyl 2-(O-alanyl)lactate as cosubstituents is described. These polymers are prepared by reaction of poly[(dichloro)phosphazene) with the corresponding amine compound. Total halogen replacement was achieved by subsequent introduction of glycine ethyl ester cosubstituents. Introduction of these hydrolysis-sensitive side-groups along the polymer chain increases the degradability of poly[(amino acid ester]phosphazenes). PMID- 1633225 TI - Haemostatic activity of ethamsylate and aminocaproic acid adsorbed poly(2 hydroxyethyl methacrylate) particles. AB - A haemostatic material suitable for embolization was prepared by the adsorption of haemostatics--ethamsylate and aminocaproic acid in the spherical particles of porous poly(2-hydroxyethyl methacrylate) (p(HEMA)). The degree of purification of ethamsylate-treated particles was tested by an analysis of donor blood in contact with the material. An evaluation of the haemostatic properties of these materials was obtained by the determination of the indicators of blood clotting: activated partial thromboplastin time, thrombin time, and prothrombin time. Ethamsylate or aminocaproic acid-containing p(HEMA) has a distinct haemostatic effect on pathological blood of patients suffering from focal alterations of the liver. These haemostatic emboli materials show promise for the immediate control of various haemorrhages; when introduced into a zone with increased haemorrhage, they may help to correct disturbed haemostasis. PMID- 1633226 TI - Minimodule dialyser for quantitative ex vivo evaluation of membrane haemocompatibility in humans: comparison of acrylonitrile copolymer, cuprophan and polysulphone hollow fibres. AB - Minimodule hollow fibre dialysers, representing clinical dialysis modules on a scale of 1/25, enable quantitative evaluation of the haemocompatibility of hollow fibre membranes in an ex vivo flow system in humans. On line heparinization, adjusted for donor sensitivity, is maintained at a minimal level (approximately 0.14 units/ml). Blood samples collected at the minimodule exit over 30 min are analysed for heparin (anti-Xa activity), activated partial thromboplastin time, fibrinopeptide A, platelet count and beta-thromboglobulin, complement fragment C3a, leucocyte count and polymorphonuclear neutrophil elastase. Initial experiments were performed using well-characterized reference materials: acrylonitrile copolymer (AN 69 HF), polysulphone and cuprophan (CUP). Activation of coagulation and platelets was low for AN 69 HF, intermediate for CUP and greatest for polysulphone, while complement activation was negligible in the presence of AN 69 HF, moderate for polysulphone and most important for CUP. Future applications will be directed towards haemocompatibility screening of prototype membranes with the aim of developing clinical dialysers with improved biocompatibility. PMID- 1633227 TI - Studies on the effect of degree of hydrophilicity on tissue response of polyurethane interpenetrating polymer networks. AB - Interpenetrating polymer networks of polyurethane and vinyl monomers such as polyacrylamide, polyvinyl pyrrolidone, poly(hydroxyethyl methacrylate) and poly(methyl methacrylate) were implanted intramuscularly in rabbits. Attempts were made to correlate the morphological aspects of the interpenetrating polymer networks to their histological response. A relatively increased hydrophilicity of hydrophobicity of the interpenetrating polymer networks as in the case of polyurethane-polyvinyl pyrrolidone and polyurethane-poly(methyl methacrylate) interpenetrating polymer networks, respectively, could elicit an inert response whilst degradation of materials promoted reactivity. PMID- 1633228 TI - In vitro erosion of 20 commercial glass ionomer cements measured using the lactic acid jet test. AB - The lactic acid jet test has been proposed for incorporation in international standards for dental cements, since results correlate well with in vivo erosion. In the literature, jet test results have been reported on only six glass ionomer cements. This study examines three types of glass ionomer, restorative, luting and metal reinforced, twenty materials from six manufacturers. A wide range of erosion rates was found particularly for restorative cements. The hypotheses put forward by previous workers to explain differences in erosion rates found on their limited range of glass ionomers do not apply to the wider range that we tested. PMID- 1633229 TI - Adsorption of glycosaminoglycans to commercially pure titanium. AB - Aqueous solutions of the glycosaminoglycans (GAG), chondroitin-4-sulphate (C4S), chondroitin-6-sulphate (C6S), heparan sulphate (HS) and hyaluronan (HY) were reacted with 5 g samples of both native and calcium-treated titanium powder (99.5% pure) for 0-48 h in 10 ml volume at 37 degrees C. Residual GAG was detected in the supernatant following recovery of the TiO2-GAG complex by centrifugation (5000 g for 1 min) as hexuronic acid using the carbazole tetraborate method of Bitter and Muir. No adsorption on to native TiO2 was evident. In contrast, prior treatment of TiO2 with calcium produced a significant adsorption of C4S to a maximum of 60 micrograms of GAG per gram Ti. Only trace amounts of C6S, HS and hyaluronan interacted in the same way. Further evidence of interaction was obtained following the liberation of bound GAG from the TiO2-Ca GAG complex with EDTA and identification using cellulose acetate electrophoresis. These findings suggest that calcium ions are required for adsorption of GAG to TiO2 which is mediated through the anionic determinants of the GAG surface and that the special configuration of C4S, the predominant chondroitin sulphate isomer found in alveolar bone, is important in the adsorption process. The implication of these findings in relation to the interaction between bone and titanium implants is discussed. PMID- 1633230 TI - Hydration and preferential molecular adsorption on titanium in vitro. AB - Surface sensitive spectroscopies, Auger electron and X-ray photoelectron (XPS), were used to determine changes in titanium oxide composition, oxide stoichiometry, and adsorbed surface species as a function of exposure to human serum in a balanced electrolyte (serum/SIE) and 8.0 mM ethylenediaminetetraacetic acid in a balanced electrolyte (EDTA/SIE) at 37 degrees C. Before immersion, the oxide was near ideal TiO2, covered by two types of hydroxyl groups: acidic OH(s) with oxygens doubly coordinated to titanium, and basic Ti-OH groups singly coordinated. After extended exposure to both solutions, up to 5000 h (ca. 208 d), the surface concentration of OH groups increased and non-elemental P appeared. The P LVV Auger transition and P 2p spectra indicated the peak positions were similar to reference phosphate compounds. The adsorbed phosphate species were presumed to be either Ti-H2PO4 or Ti-HPO4-. The XPS data suggested that a lipoprotein and/or glycolipid film was adsorbed to the specimens exposed to serum/SIE. Analysis of the preferential lipoprotein/glycolipid adsorption using electrostatic bonding concepts contributed to the refinement of the hierarchical model for the Ti-tissue interface. The salient features are that Ti metal is not in direct contact with the biological milieu, rather there is a gradual transition from the bulk metal, near-stoichiometric oxide, Ca and P substituted hydrated oxide, adsorbed lipoproteins and glycolipids, proteoglycans, collagen filaments and bundles to cells. PMID- 1633231 TI - Reaction of skeletal muscle to small implants of titanium or stainless steel: a quantitative histological and autoradiographic study. AB - Small wire implants of titanium or stainless steel were inserted into mouse leg muscles to test the reaction of regenerating skeletal muscle. Muscle fibres regenerated rapidly, starting at 3 d; by 2 wk all implants were encapsulated in thin (10 microns) fibrous tissue capsule surrounded by myotubes for 15-20 microns. Quantitatively there were no detectable differences in muscle regeneration between the two metals. The initiation of myoblast precursor cell replication was determined in regenerating muscle next to the implants. Tritiated thymidine was injected 18-156 h after implant insertion and labelled myotube nuclei in the regenerated muscle indicated that their precursors had started DNA synthesis 24 h after implant insertion. This is similar to myogenesis in many other muscle lesions and indicated that neither titanium nor stainless steel retarded muscle regeneration. PMID- 1633232 TI - [The tuberculosis of AIDS: a new tuberculosis?]. PMID- 1633233 TI - [Role of oral candidiasis as a predictive marker of tuberculosis in patients with HIV infection]. AB - We present a prospective follow-up study of 114 patient infected by Candida and HIV, in order to assess the role of oral candidiasis (OC) as a predictive marker of tuberculosis and opportunistic infections (OI) which define the Acquired Immunodeficiency Syndrome (AIDS). We compared the study group with an homogeneous control group of 152 patients infected by HIV without OC during the same period. TBC findings in the first group were discriminant with respect to the control group (p less than 0.0001) with and average period of 2.5 months between the diagnosis of OC and the development of TBC. These findings suggest that OC is an early evolutive marker of TBC and a late marker of AIDS. PMID- 1633234 TI - [Clinical-endoscopic-histologic correlations in gastric pathology. II]. AB - Some authors do not accept as valid the clinical diagnosis of gastritis, due to the latter being mainly an anatomical-pathological term. Others, however, argue that such diagnosis may be establish through a correct anamnesis. A cross sectional study of a hundred and fifty patients undergoing fibrosgastroscopy with antral biopsy and anamnesis, as well as clinical exploration in accordance with specific protocols, has been conducted. We have concluded that there does not exist as symptomatology associated to a concrete pathology, despite the presence of certain symptoms as, for example, the pain, that may be related with certain pathologies (14/20 of those developing H.H.E.D., 22/34 of those developing UB and 7/10 of those developing neoplasia). We also inferred that many of the patients (46/50) with endoscopic and histological normal findings (20/23), present as many as or more symptoms than those with pathological findings. This symptomatology may be due to a somatic disorder that could be hiding the process. PMID- 1633235 TI - [Association between post-initial remission and HLA phenotype in Type I diabetics]. AB - Our goal was to estimate the occurrence rate of the post-initial remission and its relation with HLA phenotype in type I diabetics (DMI). We studied 50 type I diabetics, 22 women and 28 men, with an average age at the onset of the disease to 15.8 +/- years (range 3-30 years). All patients were conventionally treated with insulin therapy, diet and regular exercise. Six (12%) of the diabetics presented a complete remission during 57.3 +/- 46 weeks, whereas fifteen (30%) patients presented partial remission during 20.1 +/- weeks. No significant differences were observed with regard to age at the onset of the disease, sex, BMI, initial ketoacidosis and stage of gonadal development between those diabetics presenting remission and those who did not presented so. We observed a higher incidence of the HLA-DR4 antigen among diabetics with remission (complete and partial, 61.9%), compared with patients without remission (20%, p less than 0.5). In conclusion, our results support the findings suggesting the presence of a clinical-immunological heterogenicity in DMI, genetically determined and linked to the HLA system. PMID- 1633236 TI - [Zinc and osteoporosis]. AB - The relevant role of zinc in osteoporosis, its correlation with nutrient intake and the modifications of its urinary and serum levels, have been demonstrated. In this paper, we have studied the plasmatic, urinary and intraerythrocitary levels of zinc in a group of patients with extended primary osteoporosis, most of them women with postmenopausic osteoporosis. No significant differences were observed in zinc levels between osteoporotic patients and controls. We think that certain aspects regarding the correlation between zinc and bone mineral content still have to be defined, as well as zinc intake and osteoporosis. PMID- 1633238 TI - [Late detection of Bartter's syndrome. Presentation of a case]. AB - A 27-year-old patient with a chronic clinical history of asthenia and palpitations was diagnosed with Bartter's syndrome based on clinical and biochemical criteria. This case is especially interesting due to the late detection of the syndrome, its association to hyperuricemia and hypomagnesemia and the presence of tonic-clonic convulsions. PMID- 1633237 TI - [Spinal cord compression as a primary manifestation of occult thyroid carcinoma]. AB - Metastatic disease is the first clinical manifestation of differentiated thyroid carcinoma (DTC) in less than 5% of cases. Bone metastases as the first sign of DTC are associated with a poor prognosis, both for being resistant to treatment and for complications due to them. Spinal cord compression is a rare development in DTC, which may present late in the course of the disease. An initial presentation of DTC with a spinal cord compression is an extremely rare condition. PMID- 1633239 TI - [Rhabdomyolysis and cocaine consumption: presentation of 13 cases]. AB - We present 13 cases taken care at the Emergency Service, whose diagnosis was acute rhabdomyolysis related to consumption of illicit drugs. In all cases, the presence of cocaine in the urine was detected. Clinical features, other associated factors and complications are described, stressing the etiopathogenic mechanism of presentation of cocaine-related rhabdomyolysis. PMID- 1633240 TI - [Intermittent claudication as a presenting form of hypothyroidism]. AB - Two cases of patients affected for years by intermittent claudication symptoms with normal arterial flow are presented. In both of them, the diagnosis of hypothyroid myopathy was finally established, subsiding the symptoms with the appropriate treatment. PMID- 1633241 TI - [Splenic abscess: presentation of a case and literature review]. AB - A case of a patient with splenic abscess, a rare pathology, is presented. In large hospitals, no more than 12 cases per year are usually diagnosed and they are only observed in 0.2-0.7% of all necropsies performed in North American hospitals. Its diagnosis is difficult, frequently late and, if untreated, it has a very poor prognosis. Forms of presentation, concomitant diseases, methods of diagnosis and therapeutical alternatives are discussed. PMID- 1633242 TI - [Tuberculosis and corticosteroids. Physiopathological and therapeutical implications]. PMID- 1633243 TI - [New biological parameters in the study of pleural effusions]. PMID- 1633244 TI - [Pustular arthroosteitis: diagnostic difficulty in the initial stages]. PMID- 1633245 TI - [Celiac disease and pericarditis]. PMID- 1633246 TI - [Neonatal hypothyroidism after amiodarone therapy during pregnancy]. PMID- 1633247 TI - [Kikuchi diseases: presentation of a case with severe cutaneous affliction]. PMID- 1633248 TI - [Significant increase of transaminases levels in a patient with choledocholithiasis]. PMID- 1633249 TI - [Cholestatic hepatitis from amoxicillin-clavulanic acid]. PMID- 1633250 TI - [Addison-Biermer megaloblastic anemia: Weil's encephalopathy]. PMID- 1633251 TI - [Anxiety caused by nifedipine]. PMID- 1633252 TI - [ECG alterations in extreme hyperpotassemia in a patient with a pacemaker]. PMID- 1633253 TI - [Minimal model for representing the central and peripheral pulse based on the pulse wave theory]. AB - The present paper discusses an optimized model for describing central and peripheral pulse waves. On the basis of these computer-aided calculations, further haemodynamic data may be evaluated with the aim of improving the possibilities of clinically invasive diagnostic evaluation of cardiovascular diseases. PMID- 1633254 TI - [A measuring device for calculating electrical impedance of the heart in clinical conditions]. AB - Changes in the electrical impedance of tissue can indicate structural changes. This suggests a technique for the noninvasive detection of allograft rejection after heart transplantation. The direct electrical connection to the heart and the application of a measuring current to the myocardium requires a high standard of safety. A device was developed for measuring cardiac impedance using a sinusoidal current of 20 microA at a frequency of 15 kHz. The control logic ensures a slow current onset and also an immediate cessation in case of conductor fracture or excessive voltage. Initial results in patients with normal recovery after heart transplantation revealed a rapid drop in impedance to about 70% of the initial value in the 1st 48 hours and then a stable course. In the sole rejection episode observed so far, the impedance increased again to 85% of the initial value. This paper discusses the technical safety requirements and the design of the device, and presents initial results of clinical examinations. PMID- 1633255 TI - [Biomechanically induced stimulation of postoperative bone remodeling]. AB - Bone remodelling after prosthetic surgery involving the skeleton should create a durable and intimate connection between the bone and the prosthesis. A prosthesis that is not adapted to the biological mechanics is known to cause growth reactions which may lead to failure of the biotechnical system. The stimulation of growth reactions by local, specific changes in loading is defined in this paper. Analogously to the classical laws of continuum mechanics a model for calculating the post-operative remodelling processes is developed. PMID- 1633256 TI - [Recording of data and immediate interpretation of myoelectric activity of the stomach--electrogastrography]. AB - Unlike other electrophysiological measurements such as electrocardiography (ECG) and electroencephalography (EEG), the cutaneous measurement of the electrical activity of the stomach (electrogastrography, EGG) is not an established clinical diagnostic procedure. To overcome common problems in acquiring very-low-frequency signals in the presence of large and unstable voltages we developed a real time data acquisition and analysis system based on linear-phase digital signal processing instead of analog filtering. FFT's computed on line from highly overlapping time sets are displayed as pseudo-3D or grey-scale graphic plots. PMID- 1633257 TI - Phase transitions of phospholipid vesicles under osmotic stress and in the presence of ethylene glycol. AB - The effects of poly(ethylene glycol) (PEG) on the phase transition of phospholipid multilamellar vesicles (MLVs) were investigated by using differential scanning calorimetry (DSC). Main transition temperature (Tm) and the pre-transition temperature (Tp) of neutral phospholipid-, DMPC-1, DPPC- and DSPC MLVs increased with an increase in PEG concentration. The subtransition temperature of DPPC-MLV also increased with an increase in PEG concentration. These results could be qualitatively explained by enhancement of the lateral packing on the basis of the osmoelastic coupling theory. The pretransition temperature increased faster than the main transition temperature did with an increase in PEG concentration. The increment of Tm depended on the hydrocarbon chain length, the shorter the hydrocarbon chain length was, the larger the increment was. The transition width in the DSC peak was broadened with an increase in PEG concentration. These three above-mentioned effects are the main differences between the effects of the osmotic stress on the phase transition of MLVs and those of hydrostatic pressure. On the other hand, ethylene glycol (EG), which is the monomer of PEG, had a biphasic effect on transition temperature of DPPC-, DSPC-, and DMPC-MLV, reducing Tm and Tp at low concentrations, but increasing Tm and extinguishing pretransition at high concentrations. This is explained by the induction of an interdigitated gel phase at high concentrations of EG, which indicates that EG can easily penetrate into the head group region of the lipid, in contrast with PEG 6K, because EG is small. Temperature-EG concentration phase diagrams for the various PC-MLVs were determined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1633258 TI - Acetylcholine receptor-enriched membrane vesicles in response to ethanol: activity and microcalorimetric studies. AB - The activity of acetylcholinesterase (AChE) in acetylcholine receptor (AChR) enriched membrane vesicles isolated from electric organ of Torpedo californica exhibited a biphasic response to ethanol action. Below an ethanol concentration of 35 mM, AChE activity increased with increasing concentration of ethanol. At ethanol concentrations greater than 35 mM, the activity was found to decrease montonically. In contrast, ethanol (35-400 mM) increased the activity of soluble AChE. This biphasic behavior was consistent with the proposed important role of ethanol-membrane interaction. Microcalorimetric measurements revealed that the enthalpy change in acetylcholine (ACh) hydrolysis reaction was 586 J/mol in association with membrane-bound AChE in AChR-enriched membrane vesicles, as compared to -544 J/mol with the isolated soluble AChE. This discrepancy was attributed to the presence of membranes. Unlike its action on the enzyme activity, ethanol did not affect enthalpy change in ACh hydrolysis reaction catalyzed by either membrane-bound or soluble AChE. Comparison of results on activity and heat measurements suggested that the interaction of ethanol with membrane vesicles was nonspecific with no ethanol-induced membrane structural or conformational change. PMID- 1633259 TI - Kinetics of oxygen binding and subunit assembly for the hemoglobin alpha subunit. AB - A thorough kinetic characterization of the O2-binding and self-association reactions of alpha-subunits of human hemoglobin A has been performed. All of the rate constants for a five step reaction model linking the monomer-dimer reaction to the O2-binding steps have been determined for the first time. Our analysis of the ligand binding reaction shows that both monomer and dimer have nearly identical intrinsic O2-association and dissociation rate constants and therefore identical affinities for oxygen. During this investigation we discovered a small absorbance difference between the oxy-monomer and oxy-dimer alpha-subunits. This difference spectrum enabled direct measurements of the alpha O2 self-association reaction. We find an association rate constant of, 2.0 10(5) M(-1)s-1, similar to that for other subunit assembly processes in the hemoglobin system. Our results also suggest that the deoxy-subunit assembly kinetics must be similar to that for the oxy-subunit. These kinetic results together with the equilibrium constants obtained for these solution conditions by Ackers and coworkers provides, for the first time, a complete kinetic and thermodynamic description of all the intrinsic ligand binding and association reactions for alpha-subunits. PMID- 1633260 TI - Interpretation of the X-ray scattering profiles of chromatin at various NaCl concentrations by a simple chain model. AB - In order to interpret the change in the X-ray scattering profiles from rat thymus chromatin, extensive model calculation was carried out. Chromatin is modelled as a string of subunits (nucleosomes) in which disorder is introduced into the positions of adjacent subunits. Disposition parameters characterizing the arrangement of subunits were estimated for various states of chromatin, so that the main feature of the scattering profiles is described. The result indicated that the structure of chromatin changes, as the NaCl concentration increases, from the extended "beads-on-a string" structure to the condensed helical structure. The latter has an outer diameter of about 26 nm with 3-4 nucleosomes per turn. In the intermediate state, it has a loose helical structure. The estimation of disorder suggested that the arrangement of subunits is appreciably disordered even in the condensed helical filament at 50 mM NaCl. Our model for chromatin condensation seems to support models of the "crossed linker" type. PMID- 1633261 TI - D-factor and growth hormone enhance tumor necrosis factor-induced increase of Mn superoxide dismutase mRNA and oxygen tolerance. AB - D-Factor (differentiation-inducing factor or leukemia inhibitory factor) and growth hormone are proteins that regulate growth and differentiation of cells. In this study, we demonstrated that recombinant human D-factor and growth hormone caused a slight but significant protection of adult rats against oxygen toxicity without affecting levels of pulmonary manganous superoxide dismutase (MnSOD) mRNA. D-Factor and growth hormone also markedly enhanced tumor necrosis factor (TNF)-induced oxygen tolerance. This latter effect was associated with a marked enhancement of TNF-mediated induction of pulmonary MnSOD mRNA. PMID- 1633262 TI - Further aspects of IL-1 beta secretion revealed by transfected monkey kidney cells. AB - Because the cytokine interleukin-1 beta (IL-1 beta) lacks a classical hydrophobic signal sequence, it has been unclear how it is released from cells, and whether release proceeds via a novel mechanism or through non-specific leakage. To address this issue, we have examined the secretion of the recombinant forms of human IL-1 beta from COS monkey kidney cells, which express low levels of endogenous IL-1 beta. Four proteins were expressed: precursor and mature IL-1 beta and precursor and mature IL-1 beta fused to an amino terminal hydrophobic signal sequence from human tissue plasminogen activator. By monitoring the appearance of a known cytosolic protein (ATP citrate lyase) in the medium, we find that the unmodified IL-1 beta s are non-specifically released in very small quantities from the cytosol. On the other hand, the signal sequence-modified IL-1 beta s are glycosylated and efficiently secreted by the ER/Golgi pathway. The secreted, modified-mature protein is also biologically active, suggesting that this pathway has been bypassed for reasons other than maintaining the structural integrity of IL-1 beta. More likely the alternative pathway is a critical aspect of IL-1 biology. The differences in kinetics and quantity of IL-1 beta release from monocytic and COS cells suggest that COS cells lack critical components for the rapid release seen in monocytes. PMID- 1633263 TI - In vitro production of TNF-alpha, IL-1 beta and IL-6 by mononuclear blood cells of patients with renal cell carcinoma undergoing rIL-2 treatment. Relation between clinical response and TNF-alpha production. AB - The purpose of this study was to examine the production of IL-1 beta, IL-6 and TNF-alpha by peripheral blood mononuclear cells in patients with renal cell carcinoma treated with recombinant interleukin 2 (rIL-2). Peripheral blood mononuclear cells (PBMC) were purified from blood samples obtained six times during therapy and the production of IL-1 beta, IL-6 and TNF-alpha were determined after 18 h culture of the PBMC in culture medium or in medium containing 10 micrograms lipopolysaccharide (LPS)/ml, 10 ng LPS/ml or 1000 units rIL-2/ml. In vivo therapy with rIL-2 resulted in substantial changes in the production of the three cytokines. Only the production of TNF-alpha following in vitro stimulation with rIL-2 was related to the clinical response, being significant lower in responding patients than in non-responders (P less than 0.05). These findings suggest that the rIL-2-induced TNF-alpha production of PBMC in vitro is lower in renal cancer patients that respond to rIL-2 therapy than in non-responding patients. PMID- 1633264 TI - Immunological and biological identification of tumour necrosis-like factor in sponges: endotoxin that mediates necrosis formation in xenografts. AB - Xenografts of the sponge Geodia cydonium in its closely related species G. rovinjensis resulted in a rapid rejection of the graft within a period of 5 days. We identified an immunoreactive tumour necrosis factor (TNF)-like activity in the xenograft (Mr of 30,000) two days after grafting. In-vivo injection of 5 micrograms human recombinant TNF-alpha induced cytotoxicity in sponge cells in the same pattern and time course as during natural xenograft rejection. Anti-TNF alpha polyclonals were found to react with xenograft extracts, by Western blot analysis, as from day 2 after grafting. Using ELISA we detected the TNF-like activity from day 2 after grafting with peak levels at days 4 and 5, where the amount was 0.72 ng/micrograms tissue DNA. By day 1, gp27 (inhibitory aggregation factor) is already formed in the xenograft. In-vitro experiments on isolated G. cydonium cells showed that addition of purified gp27 induced the production of the TNF-like activity (up to 13.5 ng/ml). Evidence is presented that gp27 is a product of the gp180 lectin receptor. We conclude that gp27 induces TNF-like factor production, resulting in destruction and dissolution of the xenograft after 5 days. PMID- 1633265 TI - Isolation of an mRNA encoding a soluble form of the human interleukin-6 receptor. AB - Soluble forms of the interleukin (IL)-2, IL-4 and IL-7 receptors which lack the transmembrane domain have been described. IL-6 is a growth factor important in the final differentiation of B-cells into plasma cells and in the pathogenesis of multiple myeloma. To determine whether the receptor for IL-6 may exist as a soluble molecule, RNA was analysed from the transformed B-cell lines U266, CESS and Daudi, from bone marrow from two myeloma patients, and from normal leukocytes. Using polymerase chain reaction, oligonucleotide primers which flank the transmembrane domain were selected to generate a 339 bp fragment. All samples produced equivalent amounts of the expected 339 bp fragment plus a smaller 245 bp fragment except Daudi which exhibited virtual absence of both. Sequence analysis of the smaller fragments from each of the five samples demonstrated the deletion of the entire transmembrane region from codons 356 (G-TG) to 387 (AG-G). The boundaries of this deletion were identical in all cases. Partial sequence analysis of the ligand-binding domain for U266 demonstrated identical sequences for the membrane-bound and soluble forms of the IL-6 receptor cDNAs. In summary, an mRNA which encodes a soluble form of the IL-6 receptor is expressed in both normal and myeloma cells. PMID- 1633266 TI - Characterization of monoclonal IgG antibodies produced by hybridomas derived from rheumatoid synovial cells. AB - IgM rheumatoid factors (RF) are the predominant autoantibody found in rheumatoid arthritis. They are polyclonal, fix complement, and are directed against epitopes in the Fc portion of IgG. One hypothesis regarding the induction and persistence of RF production in rheumatoid arthritis is that the Fc of IgG is somehow altered, rendering it antigenic. In this study, to better understand the derivation and pathogenicity of RF in rheumatoid arthritis, monoclonal IgG (mIgG) constitutively secreting hybridomas were established by fusing rheumatoid synovial mononuclear cells (RSC) from patients with a mouse/human heteromyeloma cell line, F3B6. To clarify the primary structure of IgG Fc constant regions produced locally by RSC, we amplified the cDNA corresponding to the CH2 and CH3 domains of an IgG1-, IgG2-, and an IgG3-producing hybridoma derived from RSC. The amplified DNA segments were cloned in M13 vectors and sequenced. Interestingly, very few differences in the nucleotide sequences were observed, and the deduced amino acid sequences were identical, except for the allotype, with those encoded by the human germline genes GEA and CL. Thus, the primary structure of the IgG1, IgG2, and IgG3 Fc regions produced by RSC were not altered when compared with those encoded by the unmutated human germline gene. These results suggest that factors other than altered IgG induce and sustain high avidity RF production in rheumatoid arthritis. PMID- 1633267 TI - Structural and functional properties of mouse-human chimeric IgD. AB - A gene encoding mouse-human chimeric secreted IgD was constructed using the rearranged murine variable region specific for the hapten dansyl and the genomic gene sequences for the constant region of the heavy (H) chain of human IgD. When expressed with the dansyl-specific chimeric light (L) chain, chimeric IgD specific for the hapten dansyl was synthesized and secreted as an H2L2 molecule. The pathway of assembly was H + L----HL----H2L2. The chimeric IgD heavy chain contains three N-linked carbohydrate moieties; one of these appears to be added co-translationally, and the other two appear to be added post-translationally. In secreted chimeric IgD some of the N-linked carbohydrate remains in the high mannose form. The chimeric IgD heavy chain also contains O-linked carbohydrate, which is added at the time of secretion. Inhibition of N-linked glycosylation with tunicamycin halts assembly at the HL half-molecule stage and prevents secretion. Like natural human IgD, the chimeric IgD binds to and upregulates the IgD receptor (IgD-R) on human peripheral blood T cells, and it is equivalent to human myeloma IgD in the competitive inhibition of rosette formation between IgD R-bearing cells and IgD-coated Ox-RBC, Cross-linking by dansyl-BSA is needed for the chimeric IgD in soluble form to cause IgD-R upregulation. PMID- 1633268 TI - The detection of anti-Ro/SS-A and anti-La/SS-B activity of human serum monoclonal immunoglobulins (monoclonal gammopathies). AB - The sera of 340 patients with monoclonal gammopathies were examined for the presence of anti-Ro/SS-A and anti-La/SS-B activity. An enzyme-linked immunosorbent assay (ELISA) technique was employed. Forty-six sera (13.5%) bound to Ro/SS-A, while 79 sera (23.2%) bound to La/SS-B. The anti-Ro/SS-A and anti La/SS-B antibodies were found in sera of patients with IgG, IgM, and IgA gammopathies. Forty-two of the 46 sera (91.3%) with positive anti-Ro/SS-A activity were found to bind La/SS-B as well, while only 53.2% (42 out of 79) of the sera that had anti-La/SS-B activity also bound Ro/SS-A. The activity against Ro/SS-A and La/SS-B was further confirmed by immunoblotting with purified immunoglobulins. Antibodies to Ro/SS-A and La/SS-B are common in systemic lupus erythematosus, Sjogren's syndrome, and other rheumatic disorders. Yet none of the patients whose serum was found to contain high titres of anti-Ro/SS-A or anti La/SS-B human monoclonal antibodies presented with symptoms related to such autoimmune diseases. Our results of a high incidence of anti-Ro/SS-A or anti La/SS-B activity in the sera of patients with monoclonal gammopathies support previous reports of autoantibody properties characteristic of these immunoglobulins. PMID- 1633269 TI - Lymphocyte surface marker expression on hybridomas secreting human monoclonal antibodies. AB - The expression of human leucocyte markers on the surface of hybridoma cell lines producing human monoclonal antibodies was studied using immunofluorescence analysis (FACS). We tested 36 different hybridoma cell lines from fusions of lymphocytes of different organs of fetal and adult organisms with the mouse myeloma line P3 X63 Ag8.653 or the mouse-human heteromyeloma line CB-F7 (IgM-, IgG-, and nonproducer) with a panel of 21 murine monoclonal antibodies against human differentiation and activation antigens. CD2, 3, 4, 5, 8, 10, 23, 25 antigen and major histocompatibility complex (MHC) class II determinants could not be detected on all hybridomas analyzed. The antigens CD22, 69, 71, and 72 were expressed on few of the hybridomas tested. The majority of the cell lines carried the surface markers CD19, 20, 40, 45 as well as the plasma cell markers CD38 and O/C11. The activation antigen 4F2 was expressed on all the cell lines tested. However, a direct connection between the expression of a lymphocyte marker and the capacity for Ig production (high and low producer; Ig isotype), the origin of the lymphocytes, and the fusion cell line used could not be detected. PMID- 1633270 TI - Characterization of an antibody to the integrin beta 3 subunit (GP IIIa) from a patient with neonatal thrombocytopenia and an inherited deficiency of GP IIb-IIIa complexes in platelets (Glanzmann's thrombasthenia). AB - Patient A.F. is a 28-year-old polytransfused woman with an inherited bleeding disorder, Glanzmann's thrombasthenia. An abnormal platelet function is linked to severe decreases in the platelet content of the integrins GP IIb and GP IIIa. In 1987 the patient gave birth to a child with severe anemia and thrombocytopenia. Serological tests revealed the presence of anti-platelet antibody together with an anti-Rhesus D. Western blotting identified a major antibody that reacted with a protein of 90-95 kDa present in platelets and endothelial cells. This was identified as the beta 3 integrin subunit (GP IIIa). Antibody-binding required intact disulfides, while controlled digestion with proteases showed the determinant(s) to be retained within chymotrypsin- (50, 63 kDa) and Staphylococcus aureus V8 protease-derived (25-38 kDa) fragments of GP IIIa. Direct binding assays performed in the presence of monoclonal antibodies specific for different epitopes on GP IIb-IIIa complexes confirmed that the epitope was exposed on intact platelets and revealed a specific inhibition of A.F. IgG binding by the monoclonal antibody, AP-3. Other tests confirmed that the antibody reacted independently of the PlA or Pen polymorphisms carried by GP IIIa. IgG purified from A.F. plasma by adsorption and elution from paraformaldehyde-fixed normal platelets or electrophoretically separated GP IIIa was an inhibitor of ADP induced platelet aggregation. Unexpectedly, Western blotting showed trace amounts of abnormally migrating GP IIIa in A.F. platelets, which retained an ability to react with her antibody. This suggests that the patient has formed an autoantibody reactive with an active site of the beta 3 integrin subunit and linked to the development of neonatal thrombocytopenia. PMID- 1633271 TI - Postnatal shift of tonotopic organization in the chick auditory cortex analogue. AB - The existence of an ontogenetic shift of tonotopic organization throughout the auditory pathway concomitant with cochlea maturation is a matter of controversy. Using the 2-deoxyglucose method we demonstrate here for the first time the shift phenomenon in an auditory forebrain structure, field L, the auditory cortex analogue of the chick. During the first postnatal month isofrequency contours move to positions where, in younger chicks, lower frequencies (up to half an octave) are represented. This developmentally changing place code of sound frequencies at the forebrain level is similar to the one previously reported for brain stem auditory nuclei. It raises the question of constancy of frequency related pitch perception during development and may be a complication of early auditory learning and memory. PMID- 1633272 TI - Unit activity to click CS changes in dorsal cochlear nucleus after conditioning. AB - Recordings were made of single unit activity (n = 360 units) from the dorsal cochlear nucleus of cats. Different patterns of activity were elicited by acoustic stimuli before and after Pavlovian conditioning. The peak response to a forward paired click conditioned stimulus (CS) increased whereas that to a backward paired hiss discriminative stimulus (DS) did not. The percentage of units responding to the CS increased from 34% to 46% after conditioning. The findings do not support the widely accepted hypothesis that learning has no effect on transmission through the first brain stem relay of the auditory system and indicate, instead, that the cochlear nucleus can participate in complex adaptive acoustic signal processing. PMID- 1633273 TI - Temporal priority of premotor cortex over nearby areas in receiving visual cues in primates. AB - Neuronal activities in the premotor cortex (PM), supplementary motor area (SMA), and precentral motor cortex (MC) were recorded while monkeys performed a visually triggered task. Kendall's partial correlation coefficient analysis was applied to the data, to determine whether changes in neuronal activity were dependent on visual-stimulus or movement-onset. The proportion of cells in which neuronal activity changes were significantly related to visual-stimulus was 22% in PM cells, 7% in SMA cells, and 0% in MC cells. The sampling populations for visual stimulus related coefficients were greatest in PM, followed by SMA, then MC. These results indicate that the PM has temporal priority over the SMA and MC in the receipt of visual cues. PMID- 1633274 TI - Projections to Botzinger expiratory neurons by dorsal and ventral respiratory group neurons. AB - Botzinger complex (BOT) augmenting expiratory neuron efferent connection are well established, but little is known concerning the afferent neural projections to BOT. The dorsal (DRG) and ventral (VRG) respiratory groups were extensively searched in 17 pentobarbital anaesthetized cats for inspiratory neurons that were anti-dromically activated from BOT. Only 1 of the 60 VRG inspiratory neurons with confirmed spinal projection was antidromically activated from BOT. Another 3 VRG inspiratory neurons and 4 of the 30 DRG inspiratory neurons were activated from BOT, but none of these neurons had confirmed spinal cord projections. All 15 early burst neurons were antidromically activated from BOT. Neural projections to BOT from DRG and VRG inspiratory neurons are rare, but neural projections from early burst neurons are common. PMID- 1633275 TI - Left hemisphere preponderance in trajectorial learning. AB - The present study examines the organisational principle of a trajectorial storage mechanism for isochronically controlled overlearned movements. 48 right-handed subjects were trained on new ideograms at five different sizes. After the trajectory had been overtrained with one hand, learning transfer to the contralateral hand was analysed. Results indicate a significant transfer of trajectorial information after training with the right hand towards the left hand which points to a preponderance of the dominant left hemisphere in generalizing storage of learned trajectories to either upper extremity. The trajectorial storage system has clear geometrical restraints. PMID- 1633276 TI - Neuropeptide Y m-RNA and peptide are transiently expressed in the developing rat spinal cord. AB - The distribution of neuropeptide Y (NPY) m-RNA and peptide were studied during the ontogeny of the rat spinal cord, by means of in situ hybridization and immunohistochemistry. NPY expressing neurons were visualized by both techniques, although by in situ hybridization they appeared slightly more abundant than by immunohistochemistry. In the ventral horn, a few neurons transiently expressed NPY from the embryonic day 15 to birth, but not in the adult animals. In the embryonic dorsal horn, NPY expressing neurons were numerous and seen as early as embryonic day 15 (E15). In contrast, in the postnatal and the adult dorsal horn, the number of neurons expressing the NPY phenotype was dramatically lower. PMID- 1633277 TI - BDNF and NGF treatment in lesioned rats: effects on cholinergic function and weight gain. AB - Effects of chronic intraventricular administration of recombinant human brain derived neurotrophic factor (rhBDNF) or recombinant human nerve growth factor (rhNGF) on presynaptic hippocampal cholinergic function in adult rats with partial fimbrial transections were measured. Partial fimbrial transections reduced synaptosomal high affinity choline uptake, choline acetyltransferase activity, and [3H] acetylcholine synthesis by approximately 50-75%. Chronic treatment with rhBDNF failed to attenuate these lesion-induced decreases. In contrast, chronic rhNGF treatment increased all three parameters by 50-90% compared to lesioned control values. Chronic treatment with rhBDNF or rhNGF attenuated weight gain of the animals. The findings failed to provide evidence for a prominent role of BDNF in the function of adult cholinergic neurons, however, they suggest an action on central neurons involved in the regulation of food intake. PMID- 1633279 TI - Cholinergically-induced theta-like oscillations in the hippocampal formation of freely moving cats. AB - The present investigation was undertaken to assess the role of the cholinergics in the production of theta (theta) rhythm in the cat hippocampal formation. Intrahippocampal injections of carbachol, muscarine or eserine produced a well synchronized high frequency cholinergic theta activity (HFC) in a range of 5-12 Hz. Subsequent intrahippocampal injection of muscarinic antagonist, atropine sulphate, completely blocked this cholinergic-induced EEG pattern. The nicotinic antagonist, hexamethonium, was without any effect on the cholinergic-induced rhythmical waves. We suggest that HFC may result from the activation of the oscillatory mechanism intrinsic to the cat hippocampal formation. PMID- 1633278 TI - Role of nitric oxide in NMDA-evoked release of [3H]-dopamine from striatal slices. AB - Evidence that excitatory amino acids act via N-methyl-D-aspartate (NMDA) receptors to evoke the release of catecholamines from axonal terminals and synaptosomes has been used to argue for the presence of pre-synaptic NMDA receptors. NMDA receptor agonists also generate nitric oxide (NO) which rapidly diffuses through neural tissue. We find that exogenously applied NO evokes [3H] dopamine release from cultured neurons. This release is not blocked by the NMDA antagonist MK-801 nor by tetrodotoxin. Both NG-nitroarginine which inhibits NO synthesis, and hemoglobin which binds extracellular NO, block NMDA-evoked [3H] dopamine release from striatal slices. A major role of endogenously-synthesized NO may be to evoke neurotransmitter release in local volumes of neural tissue. PMID- 1633280 TI - Amino alcohol modulation of hippocampal acetylcholine release. AB - The synthesis and release of 3H-acetylcholine was measured in hippocampal slices of adult rat brain following acute in vitro exposure to ethanolamine. Evoked release of 3H-acetylcholine was elevated by 60-70% but 3H-acetylcholine synthesis was unaffected. Other amino alcohols were also found to significantly increase evoked 3H-acetylcholine release. The effect may be stereochemically mediated since only one of four possible propanolamine configurations, R-alaninol, was active. The most potent compound tested was R-prolinol which showed an EC50 nearly 10-fold lower than that of either R-alaninol or ethanolamine; S-prolinol was inactive. Slices taken from adult rats which had been fed active compounds for two weeks also exhibited enhancements in evoked 3H-acetylcholine release. These results indicate that amino alcohols modulate acetylcholine release in the rat hippocampus. PMID- 1633281 TI - Age-dependent decrease in histamine H1 receptor in human brains revealed by PET. AB - Age-related changes in histamine H1 receptors were studied using [11C]pyrilamine or [11C]doxepin by positron emission tomography (PET). The frontal, parietal and temporal cortices showed age-related decreases in binding of approximately 13% per decade. In contrast, the thalamus showed no apparent decrease in binding during normal ageing because of its higher nonspecific binding. Post mortem studies also indicated that the nonspecific binding of [3H]pyrilamine in the thalamus was approximately 112% higher than that in the cortex. However, no significant decrease in histamine H1 receptors with age was observed by in vitro binding assays of autopsied human frontal cortex. Possible reasons are given for the larger effects of age observed in the PET study than in the in vitro post mortem binding study. PMID- 1633282 TI - Kainic acid injection in NTS evokes hypertension and c-fos expression in spinal cord. AB - Kainic acid injected into rat nucleus tractus solitarius (NTS) caused a slowly developing hypertension, with a 2-fold increase in Fos-immunoreactive (Fos-IR) nuclei in the area of the presympathetic bulbospinal neurons in the rostral ventrolateral medulla (RVLM) and a widespread activation of sympathetic preganglionic neurons (SPN) in the spinal cord, particularly in the mid to lower thoracic cord. The highest segmental concentration of Fos-IR SPN was in T8, with Fos-IR nuclei increased 12-fold compared with the vehicle injected group. More than 60% of retrogradely labelled sympathoadrenal neurons in T8 were Fos-IR after kainic acid injection, consistent with the 60-fold increases in plasma adrenaline levels observed in these rats. PMID- 1633283 TI - Muscimol suppresses rCGU increase in the substantia nigra after destruction of the caudate nucleus. AB - Injection of ibotenic acid into the caudate nucleus caused an increase in the uptake of 2-deoxyglucose (2DG) in the ipsilateral substantia nigra pars reticulata (SNr). Increased 2DG uptake was completely suppressed by chronic infusion of muscimol, the gamma-aminobutyric acid (GABA) agonist. While delayed shorter infusion of muscimol from the 3rd to the 7th day, when 2DG accumulation was the most prominent, partially prevented this increase. These data suggest that GABA-mediated transneuronal processes play an important role in the delayed elevation in 2DG uptake in SNR but hyperexcitation due to disinhibition by the loss of GABAergic inputs may play only a partial role in this increase. PMID- 1633284 TI - Kanji word reading process analysed by positron emission tomography. AB - Positron emission tomography, involving the H2(15)O injection technique, was used to study changes in regional cerebral blood flow during Japanese kanji word reading. Three-times intrasubject averaging analysis revealed that the main cortical responses occurred in the bilateral (left-side dominant) posterior inferior temporal area for visual input. We believe the left posterior inferior temporal area processes highly complex morphological features of kanji. For language output, left-side dominant activation of the posterior inferior frontal gyrus and the basal ganglia was found. PMID- 1633285 TI - Visually induced destabilization of human stance: neuronal control of leg muscles. AB - With subjects standing on a treadmill both the treadmill and an optical flow pattern were moved sinusoidally (0.25 Hz) and the effect of delaying the presentation of the image with respect to treadmill movement was analysed. Around the posterior turning point of treadmill movement a modulation of the tibialis anterior EMG was observed, the onset, duration and amplitude of which were dependent upon the phase-shift between the movements of the legs and the image. At times around the anterior turning point a corresponding modulation, but only of EMG amplitude, occurred in the extensor muscles. Little adaptational changes in EMG activity were seen during successive cycles. Consequently during a specific sensitive phase of the sinus tibialis anterior EMG, responses are evoked in which strength depended on the velocity of the optical flow pattern. The modulation of the extensor activity is necessary for a 'resetting' of the neutral body position. PMID- 1633286 TI - Genetically engineered toxins. PMID- 1633287 TI - The structure of plant toxins as a guide to rational design. PMID- 1633288 TI - Chemical and genetic characterization of the enzymatic activity associated with ricin A chain. PMID- 1633289 TI - Chimeric proteins containing ricin A chain. PMID- 1633290 TI - Studies on ribosome-inactivating proteins from Saponaria officinalis. PMID- 1633291 TI - Cloning and expression of trichosanthin and alpha-momorcharin cDNA. PMID- 1633292 TI - Cloning and expression of a Luffa ribosome-inactivating protein-related protein. PMID- 1633293 TI - The Aspergillus ribonucleolytic toxins (ribotoxins). PMID- 1633294 TI - An efficient expression system for alpha-sarcin in Escherichia coli. PMID- 1633295 TI - Diphtheria toxin cloning and expression in Corynebacterium diphtheriae. PMID- 1633296 TI - Genetically engineered toxins. General methods. PMID- 1633297 TI - Diphtheria toxin expression in Escherichia coli. PMID- 1633298 TI - The structure of diphtheria toxin as a guide to rational design. PMID- 1633299 TI - Protein engineering of diphtheria toxin. Development of receptor-specific cytotoxic agents for the treatment of human disease. PMID- 1633300 TI - In vivo studies with chimeric toxins. Interleukin-2 fusion toxins as immunosuppressive agents. PMID- 1633301 TI - Initial clinical experiences with an interleukin-2 fusion toxin (DAB486-IL-2). PMID- 1633302 TI - Pseudomonas aeruginosa exotoxin A. PMID- 1633303 TI - Expression of growth factor-toxin fusion proteins. PMID- 1633304 TI - Cloning strategies. PMID- 1633305 TI - The structure of Pseudomonas exotoxin A as a guide to rational design. PMID- 1633307 TI - Genetically engineered toxins in perspective. PMID- 1633306 TI - Generation of chimeric toxins. PMID- 1633308 TI - Appendix. Primary amino acid sequences of toxins. PMID- 1633309 TI - Protein engineering strategies. PMID- 1633310 TI - General strategies in in vivo animal modeling. PMID- 1633311 TI - Molecular cloning of ricin. AB - A variety of strategies have been used to obtain cDNA and genomic clones encoding ricin. Since their isolation these sequences have been manipulated to allow expression of A chain (19) and A chain mutants (15,20,34), B chain (14,21-23) and proricin (24). Utilizing structural information (35), precise changes have been introduced into both A and B chains with the aim of probing catalytic and sugar binding residues, respectively. In the longer term, such manipulations, coupled with successful expression and purification schemes, will allow the delineation of functional residues and domains, ensuring that ricin remains the prototype plant toxin with which to study cellular intoxication and ribosome inactivation and to utilize in pharmaceutical product development. PMID- 1633312 TI - Expression of plant-derived ribosome-inactivating proteins in heterologous systems. PMID- 1633313 TI - Ontogenetic aspects of the intestinal immune system in man. AB - The development of the mucosal immune system in the human fetus has been studied in some detail. Aggregates of T and B cells form early Peyer's patches by 16 weeks gestation and by 19 weeks organised Peyer's patches with T and B cell zones are seen. T cells populate the mucosal lamina propria and epithelium from 11 weeks gestation and increase in number thereafter. As in the adult, most intraepithelial lymphocytes are CD8+ and most lamina propria T cells are CD4+. By 20 weeks, villus epithelial cells are HLA-DR+ and secretory component is also expressed. In the absence of lumenal stimulation in the fetus there is no intestinal secretory IgA antibody response. A few IgA plasma cells are present in fetal salivary glands but the number does not dramatically increase until after birth. PMID- 1633314 TI - Autoimmune mechanisms in the pathogenesis of the acquired immunodeficiency syndrome. PMID- 1633315 TI - Bispecific antibodies and retargeted cellular cytotoxicity: novel approaches to cancer therapy. AB - We have used a relatively new technology to increase the number of human lymphocytes that will react with human ovarian carcinoma cells. This technology, often called "retargeting of the immune system," can temporarily redirect the activity of immune cells that were originally committed to react with foreign substances other than cancer cells. In the example presented here, the antitumor effects of retargeted human T lymphocytes, collected from normal donors, were tested in immunodeficient mice with a human ovarian carcinoma line growing intraperitoneally. We retargeted T cells in vitro with a bispecific antibody that reacted with the T cell receptor complex and with a cell-surface antigen expressed by the ovarian carcinoma cells. Retargeted lymphocytes, injected intraperitoneally into mice 4 days after intraperitoneal injection of the tumor cells, impeded tumor growth and doubled the host survival time. These findings provide support for the concept that treatment of ovarian cancer patients with retargeted T cells could prove beneficial. PMID- 1633316 TI - Bifunctional antibodies and their potential clinical applications. AB - Bifunctional antibodies are monovalent, bispecific, antibody-derived molecules. They have been produced by both chemical and biological means. They are thought to have several advantages over monoclonal antibodies in both immunotherapy and immunodiagnosis. Bifunctional antibodies have been shown to be efficient in the targeting of drugs, toxins, radiolabelled haptens and effector cells on to diseased tissues, primarily cancer cells. In addition, bifunctional antibodies have been used to develop novel immunoassays. The full potential of bifunctional antibodies has yet to be realised. PMID- 1633317 TI - Anti-idiotype vaccines in toxicology. AB - The majority of naturally occurring biological and chemical toxins are highly lethal, nonproteinaceous, low molecular weight substances which exert their toxicity through a variety of mechanisms. Their relative small size and extreme in vivo toxicity have hampered the development of protective vaccines. We have investigated the feasibility of anti-idiotype-based vaccines which utilize antibodies for inducing a systemic and protective immunity against the in vivo toxicity of some of these toxic substances. A murine IgG1 monoclonal anti-T-2 mycotoxin antibody protective against mycotoxin toxicity was generated. This antibody was used to produce a second generation monoclonal anti-idiotype antibody which was capable of serologically mimicking the tertiary conformation of the nominal antigen, i.e., T-2 mycotoxin. Administration of the monoclonal anti-idiotype antibody to mice induced a circulating and protective antibody response against the in vitro and in vivo toxicity of T-2 mycotoxin. Antibody based vaccines may represent the only safe and effective strategy for the design of protective vaccines against small nonproteinaceous toxic compounds whose extreme toxicity prevents their use as safe immunogens. The potential of antibody based vaccines for producing protective immunity against low molecular weight chemical and biological toxins is discussed. PMID- 1633318 TI - A method for detecting specific anti-C100 protein antibodies of IgM isotype in hepatitis C virus infection. AB - A method for the determination of specific IgM antibodies to C100 protein, a hepatitis C virus-associated antigen, was developed which employed fractionation of serum proteins by gel chromatography and an enzyme-linked immunosorbent assay. Detection of IgM anti-C100 proved to be specific and reproducible in purified IgM fractions. Separation of IgM from IgG was necessary before IgM could be measured, because of the detrimental effect of the simultaneous presence of IgG antibodies with anti-C100 rectivity on IgM determination. IgM anti-C100 was not found in sera containing rheumatoid factors or IgM antibodies to other hepatotropic viruses. IgM anti-C100 was detected in 19 (44%) of 43 patients with hepatitis C virus-related chronic liver disease. When compared with the histological picture of liver disease, IgM anti-C100 was absent in patients with minimal changes and was most common (66.7%) in patients with progressive disease. It is suggested that IgM anti-C100 could reflect an active state of hepatitis C virus infection. PMID- 1633319 TI - Blood zinc status and zinc treatment in human immunodeficiency virus-infected patients. AB - We investigated the zinc concentration in blood and the effect of zinc supplementation in 11 male outpatients seropositive for human immunodeficiency virus at stage 5 according to the Walter Reed classification. Zinc concentration was measured in serum, platelets, mononuclear and polymorphonuclear cells, and erythrocytes. There was a significant increase in serum zinc concentration after zinc administration, but the zinc level in blood cells remained unchanged. All patients showed a progressive gain in body weight and a slight elevation in levels of CD4+ cells. No adverse side-effects were noticed. PMID- 1633320 TI - Serum beta 2-microglobulin levels and p24 antigen, lymphocyte depletion and disease progression in human immunodeficiency virus infection. AB - Abnormally elevated serum beta 2-microglobulin levels have been associated with progression of human immunodeficiency virus disease. In this study we have analyzed the relationship between serum beta 2-microglobulin levels of patients at different stages of the disease and serological and immunological parameters commonly used for monitoring the infection. The investigation was performed on 150 patients and 30 controls during the period from March 1989 to March 1990. At that time, 30 patients had the acquired immunodeficiency syndrome or its related complex and 120 had persistent generalized lymphadenopathy or were asymptomatic. Thirty-nine antibody-negative subjects, belonging to a high-risk group for the acquired immunodeficiency syndrome, were used as controls. All patients had normal renal function. There was a significant relationship between increased serum beta 2-microglobulin levels and the presence of p24 antigen, a decrease in the total number of lymphocytes (less than or equal to 1500/mm3) and a decrease in CD4+ T lymphocytes (less than or equal to 200/mm3). No significant relationship between serum beta 2-microglobulin levels and CD3+ T lymphocytes was found. PMID- 1633321 TI - Hypereosinophilic syndromes: an update. PMID- 1633322 TI - Relation of cathepsin D level to the estrogen receptor in human breast cancer. AB - Seventy-three primary human breast cancers were analyzed to assess the presence of estrogen and progesterone receptors, the p29 protein, and the total cathepsin D status. No significant relationship was found between cathepsin D concentration and the presence of ER or PR, either by Fisher's exact test or Spearman's rank correlation (P greater than 0.1). However, a significant association was found between cathepsin D and p29 (Fisher's exact test, P less than 0.001) and between cathepsin D and steroid receptor status in samples expressing both estrogen and progesterone receptors (positive by steroid binding assay and enzyme immunoassay) (P less than 0.05). This association was more significant in tissues expressing estrogen and progesterone receptors as well as p29 (P less than 0.001). In contrast, cathepsin D synthesis was not related to tumor size, lymph node involvement, or patient's age (P greater than 0.05). Steroid receptors and cathepsin D were also assayed in samples of non-malignant tissue from 16 mastectomies; there was a significantly higher relative concentration of cathepsin D in the malignant specimens (Student's t-test, P less than 0.001). PMID- 1633323 TI - Bleeding time and antiplatelet agents in normal volunteers. AB - Clinical trials have shown that antiplatelet agents are effective in the prevention of thrombosis in arterial diseases and increase bleeding time. To compare the effects of three such drugs [acetylsalicylic acid (ASA) at two dose levels, ticlopidine and indobufen] on bleeding time, we performed a randomized cross-over study on 12 normal subjects. All received the four treatments (ASA 300 mg daily and 500 mg twice daily, ticlopidine 250 mg twice daily and indobufen 200 mg twice daily, each for 6 days plus one dose on day 7) in a sequential manner with a washout period of 15 days between the treatments. Bleeding time was measured using a Surgicut device (Ortho, Milan, Italy) before treatment, 2 and 24 h after the first administration, and before and 2, 24, 48 and 72 h after the last administration. ASA (at both doses) and indobufen quickly induced a significant prolongation of bleeding time, but the effect of indobufen soon wore off after the treatment was stopped, unlike that of ASA. In contrast, ticlopidine treatment prolonged bleeding time only after the first 24 h, and after 7 days the mean value was significantly higher than with ASA (both doses) and indobufen. This significant difference in bleeding time between ticlopidine and the other drugs was still present 48 h after the end of treatment. PMID- 1633324 TI - Fluorescent labelling of sequencing primers for automated oligonucleotide synthesis. AB - A fluorescein derivative is described which can be used as a normal phosphoramidite in oligonucleotide synthesis, giving high yields of fluorescein labelled sequencing primers. The labelled primers were used in automated DNA sequence analysis without modification of existing protocols, the computer processed sequences being reproducibly readable up to 400 bases. The procedure described makes the fluorescent labelling of oligonucleotides much easier, and the time of labelling can be significantly reduced. It speeds up the "primer walking" approach of automated DNA sequencing. PMID- 1633325 TI - DNA sequencing by a subcloning-walking strategy using a specific and semi-random primer in the polymerase chain reaction. AB - In its basic concept, in vitro DNA amplification by the polymerase chain reaction (PCR) is restricted to those instances in which segments of known sequence flank the fragment to be amplified. Recently, techniques have been developed for amplification of unknown DNA sequences. These techniques, however, are dependent on the presence of suitable restriction endonuclease sites. Here, we describe a strategy for PCR amplification of DNA that lies outside the boundaries of known sequence. It is based on the use of one specific primer, homologous to the known sequence, and one semi-random primer. Restriction sites in the 5' proximal regions of both primers allow for cloning of the amplified DNA in a suitable sequencing vector or any other vector. It was shown by sequence analysis that the cloned DNA fragments represent contiguous DNA fragments that are flanked at one side by the sequence of the specific primer. When omitting the semi-random primer, a single clone was obtained, which originated from PCR amplification of target DNA by the specific primer in both directions. PMID- 1633326 TI - Rapid and reliable fluorescent cycle sequencing of double-stranded templates. AB - Automated DNA sequencing is an extremely valuable technique which requires very high quality DNA templates to be carried out successfully. While it has been possible to readily produce large numbers of such templates from M13 or other single-stranded vectors for several years, the sequencing of double-stranded DNA templates using the ABI 373 DNA Sequencer has had a considerably lower success rate. We describe how the combination of a new fluorescent, dideoxy sequencing method, called cycle-sequencing, coupled with modifications to template isolation procedures based on Qiagen columns, makes fluorescent sequencing of double stranded templates a reliable procedure. From a single five milliliter culture enough DNA can be isolated (up to 20 micrograms) to do 4-8 sequencing reactions, each of which yields 400-500 bases of high quality sequence data. These procedures make the routine use of double-stranded DNA templates a viable strategy in automated DNA sequencing projects. PMID- 1633327 TI - Conserved signals in the 5' flanking region of eukaryotic nuclear tRNA genes. AB - The statistical analysis of 5' flanking regions of eukaryotic tRNA genes was done. The analysis of nucleotides in the sequence of fungi and invertebrates showed a high content of A and T in the flanking regions versus coding regions where G and C dominate. In contrast to these results in vertebrates sequences the preferences of any nucleotide in flanking regions was not observed. The analysis of tetrads showed five conserved signals: TTGT, (T/A)(T/A)ATA, A(C/T)(C/A)A in the tRNA genes of fungi, (A/T)TGA of invertebrates and (A/T)GAG of vertebrates. The analysis of 3' flanking regions did not show any conserved signals except well known poly-T tracks. PMID- 1633329 TI - Characterization of the primate-specific repetitive DNA element MER1. AB - Computer analyses of the 3'-flanking DNA sequence of the human elastase I gene revealed a significant degree of similarity with seven human gene sequences in the GenBank and EMBL databases. Genomic Southern analysis indicates that the shared nucleotide sequences are a primate-specific family of short interspersed elements. These elements are members of MER1 sequences (medium reiteration frequency sequences). The consensus sequence of MER1 repeats spans 543 nucleotides and contains several inverted repeats. Since the copy number of MER1 elements seems to be much smaller than that of Alu and L1 repeats, MER1 elements may provide useful landmarks marks for human genome mapping. PMID- 1633328 TI - Genomic organization of the human homologue of the rat pancreatic elastase I gene. AB - The homologue of the rat pancreatic elastase I gene was found in the human genome, but its transcription was completely suppressed in the adult human pancreas as we reported previously. In this study, we characterized the complete structure of the eight putative exons of the silent gene for human elastase I. A genotype analysis of the exon 1 DNA sequence revealed that at least two allelic elastase I genes are present in human genomes. A primate-specific repetitive DNA element (MER1) was identified in the 3'-flanking region of the human elastase I gene. The primary structure of human preproelastase I, deduced from the sequences of the eight exons, showed an 89% identity with that of porcine or rat pancreatic preproelastase I. The amino acid residues of the serine protease catalytic triad and the eight cysteine residues conserved in the elastase family were present at positions equivalent to those observed in porcine and rat elastase I, suggesting that the gene product may function as an elastolytic enzyme if this gene is expressed in any tissue. PMID- 1633331 TI - A memorial issue to Bernard L. Diamond. PMID- 1633330 TI - Difference in the genomic organizations of the related transcription factors Sp1 and Krox-20; possible evolutionary significance. AB - We report here part of the genomic sequence of the mouse homolog of the human gene encoding the transcription factor Sp1. This gene belongs to a subfamily of zinc finger proteins, which includes another transcription factor, Krox-20. The analysis of the mouse Sp1 nucleotide sequence revealed that (i) the C-terminal part of the protein is conserved between man and mouse, consistent with a possible role in transcriptional activation; (ii) while the there Krox-20 zinc fingers are encoded by a unique exon, an intron separates the regions encoding fingers 2 and 3 of Sp1. On the basis of this latter observation, we propose a model for the evolution of the Sp1/Krox-20 gene family which might shed some light on the role of introns in the evolution of modular proteins. PMID- 1633332 TI - In memoriam: Bernard L. Diamond December 8, 1912-November 18, 1990. PMID- 1633333 TI - The forensic psychiatrist: consultant versus activist in legal doctrine. PMID- 1633334 TI - A personal view of the ethics and values of Bernard L. Diamond. PMID- 1633335 TI - "The Fallacy of the Impartial Expert" revisited. AB - This article, in memory of Bernard Diamond, revisits his seminal editorial on the "Fallacy of the Impartial Expert." In a later article he formulated his thesis most succinctly: "There is no such thing as an impartial expert witness; the objectivity of the expert witness is largely a myth." I argue that the implications of his challenging assertion have as yet not been fully recognized. Ultimately, they also invite a revision of the American Academy of Psychiatry and Law's Guidelines for the Practice of Forensic Psychiatry. The Guidelines should emphasize more than they do experts' commitment to honesty and to informing fact finders about the extent and limits of their scientific knowledge, the facts on which their opinions are based, as well as the scientific and value assumptions that underlie their testimony. PMID- 1633336 TI - Forensic psychiatry: the need for self-regulation. AB - The shortcomings of forensic psychiatrists in the courtroom fall into two categories: failure to meet expected levels of performance in evaluation and testimony; and unethical behavior or deliberate misfeasance. Legal mechanisms for controlling the quality of testimony have been inadequate to the task. Courts rarely make use of their powers to screen expert witnesses with care; and post hoc remedies, such as malpractice actions or charges of perjury, are almost unheard of. Psychiatry has been equally ineffective to date in responding to these problems, with educational programs usually reaching those least in need of help, and ethical codes either not addressing forensic issues or lacking powers of enforcement. Each class of problem calls for a distinct response. Inadequate performance in forensic work can be monitored and corrected by implementation of a program of peer review of forensic testimony. Preliminary attempts indicate the feasibility and utility of this effort. Unethical behavior, on the other hand, should be addressed by clear standards of forensic ethics, enforced by the relevant professional organizations. Forensic psychiatry bears the responsibility of cleaning its own house. PMID- 1633337 TI - Professional versus personal ethics: methods for system reform? AB - It has been suggested that changes in, and more vigorous enforcement of, professional ethical codes might lead to significant improvements in the quality of expert testimony by mental health professionals. The author examines the arguments for and against this thesis, and concludes that lack of consensus on controversial issues is likely to impede implementation and enforcement of meaningful ethical codes. He argues that attempts to educate the courts and legislatures through writings, testimony, and interdisciplinary teaching are more likely to be effective for the foreseeable future. PMID- 1633338 TI - Diminished capacity as an alternative to McNaghten in California law. AB - Dr. Diamond's courageous defense of the diminished capacity plea in People v. Gorshen (1959) emphasized mental disturbances negating malice aforethought. Diminished capacity as a defense in California remained effective from 1978 to 1982 until overturned by a modified American Law Institute rule. Diamond's advocacy of psychologic elements, including motivation, did much to enliven forensic thinking re: the death sentence and the fated diminished capacity defense. PMID- 1633339 TI - "Therapist-patient sex syndrome": the perils of nomenclature for the forensic psychiatrist. AB - The escalating problem of sexual misconduct has heightened clinicians' awareness of the consequences of therapist-patient sexual relations. One consciousness raising device, the definition of "therapist-patient sex syndrome," may pose more problems than remedies in the forensic, rather than clinical context. The author reviews the conceptual, diagnostic, and teleological dimensions of this addition to diagnostic nomenclature. PMID- 1633340 TI - "A terror to their neighbors": beliefs about mental disorder and violence in historical and cultural perspective. AB - This tribute to the enduring legacy of Bernard Diamond explores public perceptions of a link between mental disorder and violent behavior. Research on contemporary American beliefs is summarized and compared both to historical accounts of public perceptions in Western cultures and to anthropological investigations of public perceptions in non-Western cultures. The conclusion of these reviews is that the belief that mental disorder bears some moderate association with violent behavior is both historically invariant and culturally universal. PMID- 1633341 TI - The death penalty and Bernard Diamond's approach to forensic psychiatry. AB - Bernard Diamond would testify only for the defense in criminal cases, but only if the whole psychiatric truth would be introduced during a trial and the facts of the case supported the defense position. Otherwise, he would refuse to participate. Although few other forensic psychiatrists have personal or professional ethical concerns regarding ever participating for the prosecution, many more have such problems in capital cases. Bernard Diamond's approach to forensic psychiatry should be considered at least as an option by those opposed to the death penalty. Bias in capital cases is not a persuasive reason to withdraw from involvement if the forensic psychiatrist remains honest. PMID- 1633342 TI - The evolution of legal methods for dealing with mind-state in crimes. AB - From its very beginnings, British and American common law have attempted to deal with the mind-state of perpetrators of crime. This has taken various procedural and statutory forms that have often been characterized by confusion and contradictions in purpose. Clarification of the psychological and legal issues may assist in bringing the criminal treatment process to a more rational basis. PMID- 1633343 TI - Clinical assessment of the voluntariness of behavior. AB - There are a variety of therapeutic and forensic contexts in which the clinician is called upon to assess the voluntariness of behavior. Because the assessment has such complex moral and scientific dimensions, it has been difficult to conceptualize how it is done. By considering the behavior of clinicians and other relevant theoretical issues, the author has prepared a framework for thinking about the assessment of voluntariness. The relevance of diagnostic and philosophical issues is considered. Most of the factors which influence assessment are related to the nature of the patient's pathological experience, hypotheses of causation, and method of treatment. Dr. Diamond had a deep interest in questions of voluntariness and responsibility. I know that he would have disagreed with, at least, some of the material, but I believe that he would have thoroughly enjoyed discussing and arguing the issues. I know that I would have loved the dialogue. PMID- 1633344 TI - Nocturnal blood pressure monitored by ambulatory blood pressure measurement in elderly hypertensive patients. AB - This study was designed to characterize the nocturnal fall of blood pressure (NFBP) of elderly hypertensive patients (EH), with or without cerebrovascular disease or diabetes mellitus, as measured by automated blood pressure (BP) monitoring. Systolic and diastolic BP and heart rate was measured every 15 minutes in 133 hospitalized patients with nearly similar schedules and diets. The patients were divided into five groups: I, normotensive elderly patients over age 65: II, EH without cardiovascular diseases, controlled without medication: III, EH with cerebral infarction, chronic stage: IV, EH with noninsulin-dependent diabetes mellitus: and V, hypertensives under age 65, without cardiovascular diseases. A significant NFBP was observed in the patients of groups I and V, a significant but smaller NFBP in the hypertensives of groups II and IV, and no NFBP in the patients of group III. Administration of the antihypertensive drugs, enalapril and nifedipine, tended to augment the NFBP. These preliminary observations showed that NFBP did occur in elderly hypertensives but the fall was smaller than that observed in younger hypertensives or elderly normotensives. Although the ambulatory BP measurements were useful in the overall clinical evaluation of elderly patients, NFBP in elderly patients was affected by hypertensive drugs and therefore NFBP should be interpreted with caution. PMID- 1633345 TI - Diurnal change in heart rate variability in healthy and diabetic subjects. AB - We assessed the hourly coefficient of variance of RR intervals (CVRR) in 29 subjects with non-insulin-dependent diabetes mellitus and 19 age-matched healthy subjects using an ambulatory 24-hour ECG monitoring system. We also evaluated CVRR during 100 beats in both groups in the supine posture at 07:00 and 10:00 in the morning. Hourly CVRR showed an overt diurnal variation in both groups especially in the daytime and at midnight, but was significantly lower (p less than 0.05) in diabetic patients. CVRR during resting 100 beats at 07:00 was significantly higher (p less than 0.05) than that at 10:00 in both groups. These findings indicate that HRV shows an obvious diurnal variation in both groups. As a steep and marked change occurs in the morning, careful consideration is necessary to assess the test performed for a short time span at random times throughout the day, particularly in the morning. PMID- 1633346 TI - Diffuse pulmonary alveolar hemorrhage in acute promyelocytic leukemia. AB - A 60-year-old male with acute promyelocytic leukemia demonstrated bilateral diffuse air-space consolidation on chest X-ray. An autopsy on the next day revealed pure pulmonary alveolar hemorrhage without leukemic infiltration or inflammation. Disseminated intravascular coagulation was confirmed microscopically. In severe hemorrhagic diathesis and leukopenia, it is impossible to distinguish pulmonary hemorrhage from pneumonia by X-ray alone. Bronchalveolar lavage may be the only possible diagnostic approach. PMID- 1633347 TI - A case of papillary carcinoma of the thyroid associated with parathyroid adenoma without hyperparathyroidism. AB - A rare occurrence of the association of parathyroid adenoma in a case of thyroid papillary carcinoma is described. The patient was incidentally found to have parathyroid adenoma which was preoperatively diagnosed to be a metastatic lymph node. Analysis of her serum obtained before operation showed an elevation of serum parathyroid hormone (PTH) concentration without hypercalcemia. Since the association of hyperparathyroidism is high in patients with thyroid diseases, examination of not only serum levels of calcium and PTH but also careful interpretation of computed tomography (CT) and/or nuclear magnetic imaging (MRI) is necessary in the diagnosis of co-existing asymptomatic hyperparathyroidism. PMID- 1633348 TI - Syndrome of inappropriate secretion of antidiuretic hormone associated with multiple sclerosis. AB - A 63-year-old man who developed episodes of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) twice in the course of multiple sclerosis (MS) is reported. SIADH in this patient occurred only during the administration of antibiotics (sulbactam/cefoperazone, SBT/CPZ). At autopsy, demyelinating lesions in the optic nerves, cervical and thoracic spinal cord, and areas adjacent to the lateral ventricles were observed. Destruction and loss of neuronal cells were found in the supraoptic nuclei. Lymphocytic infiltration was observed in the area adjacent to the supraoptic nuclei. Destruction and swelling of axons and reactive astrocytic gliosis were observed in the hypothalamus. SIADH associated with MS is rare and the histological findings in such a case have not yet been reported. It is suggested that the development of SIADH in MS may be related to the damage in the supraoptic nuclei of the hypothalamus. PMID- 1633349 TI - Acute adrenal insufficiency due to symptomatic Rathke's cleft cyst. AB - A 65-year-old Japanese man who suffered from secondary hypopituitarism due to Rathke's cleft cyst is reported. Although computed tomography failed to detect any pituitary abnormality, magnetic resonance imaging demonstrated the presence of a cystic intrasellar mass, initially suggesting craniopharyngioma or abscess. Operative findings revealed Rathke's cleft cysts within the pituitary fossa which resulted in secondary hypopituitarism. Among cases of secondary hypopituitarism with abnormal findings in the pituitary, symptomatic Rathke's cleft cysts should be included in the differential diagnosis of adrenal insufficiency. PMID- 1633350 TI - Four Japanese cases of episodic angioedema with eosinophilia. AB - Here we describe four young Japanese women aged 25-33 years, whose clinical findings are characterized by episodic angioedema, marked leukocytosis with eosinophilia, benign course with spontaneous remission or low-dose prednisolone treatment. The recognized causes of eosinophilia, such as allergy, parasite, and collagen diseases, and the causes of edema, such as heart, kidney, and liver diseases, were ruled out. The findings in these patients are very similar to those reported as episodic angioedema with eosinophilia, which is clearly distinct from the so-called hypereosinophilic syndrome. We suggest that this syndrome is not rare, and should be widely recognized as a new clinical entity for accurate and prompt diagnosis. PMID- 1633351 TI - Sjogren's syndrome with hydronephrosis caused by pseudolymphoma. AB - A 67-year-old woman with Sjogren's syndrome was found to have left hydronephrosis and stenosis of the left ureter. Exploratory laparotomy disclosed a nodule at the ureteropelvic junction of the left ureter. Histopathological examinations of the biopsied specimen of this nodule showed lymphoid hyperplasia within the ureteral wall. Low dose prednisolone improved hydronephrosis and pseudolymphoma within several months. Hydronephrosis secondary to pseudo-lymphomatous infiltration of the ureter is a rare but, if properly treated, reversible complication of Sjogren's syndrome. PMID- 1633352 TI - A case of anorexia nervosa with acute renal failure induced by rhabdomyolysis; possible involvement of hypophosphatemia or phosphate depletion. AB - A 16-year-old girl with anorexia nervosa first presented with malnutrition, liver dysfunction, and rhabdomyolysis. Administration of fluid and nutrition saved her from the initial critical state, but acute renal failure followed. Laboratory examination revealed intrinsic renal failure induced by rhabdomyolysis. Latent phosphate depletion and refeeding-induced hypophosphatemia was implicated as the cause of rhabdomyolysis; however coexisting hypotension, dehydration, and liver dysfunction may have contributed to the renal failure. The patient recovered from azotemia by hemodialysis. This is the first reported case of anorexia nervosa with acute renal failure resulting from rhabdomyolysis induced by hypophosphatemia or phosphate depletion. PMID- 1633353 TI - Sideroblastic anemia associated with multiple myeloma in Turner's syndrome. AB - A 67-year-old female was admitted to our hospital because of pancytopenia. Forty six percent of erythroblasts in the bone marrow were ringed sideroblasts. Laboratory findings showed an IgG-kappa monoclonal gammopathy. She was diagnosed as having sideroblastic anemia associated with multiple myeloma in mosaic (45, X/46, XX/47, XXX) Turner's syndrome. There was no response to therapy. The chromosomal pattern of the patient was varied, and was accompanied by the development of refractory anemia with an excess of blasts from refractory anemia with ringed sideroblast 4 months after presentation. Cytogenetic studies suggested that the abnormal clone was restricted to the monosomic cell line. PMID- 1633354 TI - Electrical alternans of the T-U wave without change in the QRS complex. AB - A patient with myelocytic leukemia who showed electrical alternans of the T-U wave with no change in the QRS complex following chemotherapy is described. Electrocardiogram taken 4 days later showed ventricular quadrigeminy in which the T-U wave of the first sinus beat after the ventricular premature contraction was markedly less prominent compared to the successive two sinus beats which showed marked prolongation and inverted T-U waves. The causative factors for alternans of T-U waves may include hypochloremic alkalosis with hypopotassemia and myocardial damage by anticancer drugs such as daunomycin and aclarubicin chloride used for the underlying disease. PMID- 1633355 TI - Multiple osteomyelitis due to Mycobacterium avium with no pulmonary presentation in a patient of sarcoidosis. AB - A 31-year-old man with multiple osteomyelitis due to Mycobacterium avium is reported. The patient had been on prednisolone for systemic lymphadenopathy which was thought to be caused by sarcoidosis. In June 1990, he noticed high fever and general bone pain. He was found to have multiple lytic lesions in the bones which were biopsied showing acid-fast bacilli. This organism was revealed to be M. avium. The chest radiograph film revealed no abnormal pulmonary findings. Multiple bone lesions in the absence of pulmonary disease is reported to be rare for atypical mycobacterial infection. PMID- 1633356 TI - Development of rheumatoid arthritis after chronic hepatitis caused by hepatitis C virus infection. AB - We describe a patient with rheumatoid arthritis (RA) who had preceding evidence of post-transfusion, non-A, non-B hepatitis. The patient showed positive serological tests for anti-hepatitis C virus (HCV) antibody. The manifestations of RA, including progressive polyarthritis and positive serum rheumatoid factors, emerged after the ameriolation of hepatitis and persisted for more than 3 years, indicating that the polyarthritis in this patient was not the prodrome of the hepatitis. This patient had HLA-DR4 and HLA-Bw54 which are found to be strongly associated with RA in Japan. It is therefore suggested that HCV may trigger the development of RA especially in genetically susceptible individuals. PMID- 1633357 TI - A case of malignant lymphoma accompanied by Klinefelter's syndrome. AB - A 66-year-old Japanese male with diffuse non-Hodgkin's lymphoma, of the pleomorphic type, complicated with Klinefelter's syndrome is reported. His phisique was characterized by a long arm span, disproportionately longer lower body dimensions and a small sized penis. He had no children. Chromosomal study revealed 47, XXY and hormonal quantification showed hypergonadtropic hypogonadism. Although chemotherapy was administered, his disease took a progressive course and he died. A discussion of chromosomal alteration and oncogenesis and review of the literature are included. PMID- 1633359 TI - An outbreak of Legionnaires' pneumonia in a nursing home. AB - An outbreak of Legionnaires' pneumonia occurred at a nursing home in December 1990. A 79-year-old female and a 73-year-old male clerk who were staying at the nursing home developed pneumonia with only a 5-day interval. Legionella pneumophila serogroup I was isolated from transtracheal aspirate of the former and sputum of the latter. After treatment with a combination of erythromycin and rifampicin both patients improved. Serological surveillance of inpatients and staff of the nursing home was performed in February 1991. Seven out of 51 samples (14.0%) showed a titer higher than 1:128 of anti-Legionella pneumophila serogroup I antibody determined by indirect immunofluorescence; two of these seven complained of respiratory symptoms. Molecular epidemiology analyzed by restriction endonuclease digestion of isolated L. pneumophila showed an identical pattern which suggested a common origin. PMID- 1633358 TI - Ticlopidine treatment in idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia accompanied by nephrotic syndrome. AB - A 36-year-old woman was admitted for idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia (IPL) associated with nephrotic syndrome. She was expected to lapse into renal failure because renal biopsy showed focal glomerulosclerosis. VEMP chemotherapy and bolus methyl prednisolone were not effective against excessive urine protein of over 10 g/day. We thus began administration of ticlopidine (6 mg/kg/day), prednisolone (0.4 mg/kg/day) and cyclophosphamide (1 mg/kg/day). After 3 months of this regimen, the urine protein level decreased to less than 0.5 g/day, and renal function was maintained for more than 3 years. It is suggested that ticlopidine is effective for nephropathy complications associated with IPL. PMID- 1633360 TI - Primary epidural non-Hodgkin's lymphoma in clinical stage IEA presenting with paraplegia and showing complete recovery after combination therapy. AB - A 70-year-old man was admitted to our hospital because of paraplegia. A spinal epidural tumor (Th VII-XI) was diagnosed by magnetic resonance imaging and resected. Histological examination of the tumor showed non-Hodgkin's lymphoma of the diffuse large cell type (Lymphoma Study Group classification), with a B cell phenotype. The clinical stage was IEA by the Ann Arbor classification. Radiation therapy of the involved field was performed (total dose: 40 Gy), followed by six courses of modified cyclophosphamide, adriamycine, vincristine, prednisolone (CHOP) therapy. He was discharged walking unaided 10 months later and has shown no evidence of relapse in the 26 months since discharge. PMID- 1633362 TI - A patient with protein-losing enteropathy associated with systemic lupus erythematosus. AB - A 46-year-old woman previously diagnosed as having systemic lupus erythematosus presented with severe hypoalbuminemia and anasarca. She was demonstrated to have protein-losing enteropathy without any other active symptoms of SLE. Her bowel habit was normal and endoscopic examination revealed non-specific colitis and a small ulcer in the duodenum. Serum biochemistry showed an abnormal profile of the serum protein, including severe hyperlipoproteinemia and hyperfibrinogenemia. The process of protein-losing was not selective in terms of the molecular size. All of these symptoms and the abnormalities in laboratory data were improved by corticosteroid therapy. PMID- 1633361 TI - A case of common bile duct stone with cholangitis presenting an extraordinarily high serum CA19-9 value. AB - A 63-year-old male complained of right upper abdominal pain and jaundice. Laboratory data on admission showed hyperbilirubinemia, elevation of biliary enzymes and an extraordinarily high value of serum CA19-9 (60,000 U/ml). Diagnostic imaging modalities including abdominal ultrasonogram, abdominal CT and PTC suggested a stone impaction of the common bile duct. Jaundice subsided after PTC-drainage in association with decreasing serum CA19-9 value, which returned to the normal level six weeks later. Spontaneous delivery of the stone via the fistula was confirmed by cholangiography through the drainage tube. Though there are few reports of such a high serum CA19-9 level, the possibility of benign biliary tract disease should be considered in patients showing an extraordinarily high serum CA19-9 value. PMID- 1633363 TI - Lung cancer with eosinophilia in the peripheral blood and the pleural fluid. AB - A case of lung cancer associated with eosinophilia in the peripheral blood and pleural fluid is reported. A 55-year-old man with a tumor in the right lower lung lobe and right pleural effusion was admitted to Ehime University Hospital. Histology of specimens biopsied under a bronchoscope revealed that he had poorly differentiated squamous cell carcinoma. On admission, his peripheral blood leukocyte count was 11,500/microliters with 7.8% eosinophils and the pleural fluid showed a high eosinophil count (60.5%). After chemotherapy, blood eosinophilia disappeared and the pleural effusion was decreased with the reduction of the tumor. The patient's serum had the activity to stimulate eosinophil proliferation in human bone marrow cell culture, suggesting that the tumor may have produced an eosinophil proliferating factor. PMID- 1633364 TI - Hypertension in an adult with unilateral renal dysplasia. AB - We report a 29-year-old Japanese female with severe hypertension and unilateral renal dysplasia, which is rarely found in adults. The involved kidney was surgically removed and then the blood pressure fell to borderline levels without any changes in plasma renin activity or plasma aldosterone concentration. Histological examinations revealed typical renal dysplasia without hyperplasia of the juxtaglomerular apparatus. Unilateral renal dysplasia may be a cause of secondary hypertension in adults, though the mechanisms are still unknown. PMID- 1633365 TI - Allergic granulomatosis and angiitis with severe cardiac disease: a case in which cardiac function was extremely improved by long-term steroid therapy. AB - A 38-year-old man with a history of bronchial asthma developed marked eosinophilia, mononeuritis multiplex and transient pulmonary infiltration. Pathological findings from the lung and nerve biopsy were helpful in determining the diagnosis as allergic granulomatosis and angiitis (AGA). Echocardiogram indicated dilation of the left ventricle with impaired systolic contraction. Coronary arteriography demonstrated significant stenosis only in the peripheral segment of the circumflex artery. After 1 year of corticosteroid therapy, echocardiogram revealed improvement of left ventricular contractility evaluated by ejection fraction (from 28% to 67%). To our knowledge, no previous reports have described amelioration of severe cardiac lesions during long-term steroid treatment in patients with AGA. PMID- 1633366 TI - Superinfection of chronic necrotizing pulmonary aspergillosis by Mycobacterium tuberculosis. AB - A 63-year-old woman with chronic necrotizing pulmonary aspergillosis complicated by active pulmonary tuberculosis is reported. A small infiltrative shadow appeared, but no definite diagnosis was made. Six years later the shadow was found to have increased in size; chest CT revealed a fungus ball, while a transbronchial lung biopsy revealed aspergillus hyphae. The intrabronchial inoculation of amphotericin B proved ineffective, and a lobectomy was performed. Histopathologic findings showed necrotic granulomas containing aspergillus and some acid-fast bacilli. While the superinfection of healed tuberculous lesions by Mycobacteria or Aspergillus species is well documented, their coexistence is rare. PMID- 1633367 TI - Successful treatment of primary amyloidosis with dimethylsulfoxide and cytoreductive chemotherapy. AB - A 42-year-old Japanese male was admitted to our hospital because of congestive heart failure (CHF). A diagnosis of primary amyloidosis was made on the basis of a heavy deposition of amyloid in the gastric submucosal tissue in addition to the hematological and immunological findings. Intermittent chemotherapy in combination with daily oral dimethylsulfoxide (DMSO) resulted in a dramatic decrease of plasma cells in the marrow as well as a gradual improvement of CHF. With this therapy, the cardiac ejection fraction was markedly improved. This case indicates that the long-standing administration of DMSO combined with cytoreductive chemotherapy is therefore effective in treating some cases with primary amyloidosis. PMID- 1633368 TI - Successful treatment of idiopathic plasmacytic lymphadenopathy with polyclonal hypergammaglobulinemia. AB - A 51-year-old male was admitted because of eyelid edema and anosmia, which developed in 1985. He showed bilateral cervical lymphadenopathy, with nodes larger than 2 x 2 cm, and remarkable eyelid edema. Anemia, hyperimmunoglobulinemia with hypo-albuminemia (no M-protein) and liver dysfunction were found. Bone marrow, renal function, urine analysis and LDH level were normal. Cervical lymph node biopsy showed interfollicular proliferation of plasma cells without any malignant appearance. On day 3 of oral prednisolone (PD), anosmia abruptly improved from day 7, eyelid swelling, cervical lymphadenopathy and gammopathy subsided gradually. Since PD was tapered off, no relapse has been observed thus far. PMID- 1633369 TI - Multiple space-occupying lesions of the spleen in a case of Gaucher's disease. AB - A 50-year-old female patient was admitted because of an enormously enlarged spleen and thrombocytopenia. Ultrasonography and magnetic resonance imaging revealed multiple space-occupying lesions in the spleen. She was diagnosed as having Gaucher's disease based on the low level of beta-glucosidase activity in leukocytes and Gaucher's cells present in bone marrow aspirate. Severe hypersplenism necessitated splenectomy. Pathological studies of the excised spleen, including ultrastructural examinations, demonstrated that multiple space occupying lesions in the spleen were composed of typical Gaucher cells. PMID- 1633370 TI - Hypocalcemic cardiomyopathy in a patient with idiopathic hypoparathyroidism. AB - An idiopathic hypoparathyroidism-induced cardiomyopathy patient had severe long lasting hypocalcemia. The dramatic improvement of cardiac function with correction of only the serum calcium concentration could be quantitatively demonstrated on both echocardiogram and ventriculogram. The concentration of the extracellular calcium ion was considered to have a direct effect on the strength of the myocardial contraction through excitation-contraction coupling. Furthermore, elevated serum creatine phosphokinase and lactate dehydrogenase levels which were thought to be delivered from skeletal muscle returned to the normal range concomitant with the correction of hypocalcemia. The serum calcium concentration and these enzyme level showed significant inverse correlations. PMID- 1633371 TI - Primary esophageal non-Hodgkin's lymphoma. AB - A 77-year-old woman with primary esophageal non-Hodgkin's lymphoma in clinical stage IEA (Ann Arbor Classification) developed pain and difficulty in swallowing. An upper gastrointestinal examination revealed a submucosal tumor from the upper to the middle portion of the esophagus. Histopathological examination at endoscopic biopsy with endoscopic partial incision showed non-Hodgkin's lymphoma (diffuse type--large cell). Immunohistological examination of tumor cells disclosed LCA (+), CD3(DAKO) (+), MT1 (+), UCHL1 (+), MB1 (+), MxPanB (-) and EMA (-) reactivity and showed T cell lymphoma. The clinical stage was determined to be IEA after further work-up. Improvement of swallowing difficulty and esophageal findings on upper gastrointestinal series were noted after modified CHOP therapy and radiotherapy (total 50 Gy). PMID- 1633372 TI - Lyme disease acquired outside of Japan. PMID- 1633373 TI - Clinical management of chronic pain in spinal cord injury. AB - Spinal cord injury (SCI) can cause paralysis; sensory impairment; autonomic nervous system dysfunction; and bowel, bladder, and sexual dysfunction. These impairments may lead to immobility, physical dependence, and alterations in lifestyle and self-esteem. The addition of chronic, intractable pain to these impairments can be truly devastating. Chronic pain superimposed on spinal cord injury can virtually drain the individual of strength, motivation, and will. For the spinal cord injury survivor who already faces functional loss, severe pain can further restrict even the diversional activities that are available. Thus, it may become impossible for the individual to escape his or her pain even temporarily. The various medical, physical, and surgical treatments considered to be efficacious in treating this pain are reviewed. However, although chronic pain in SCI may be managed by these therapies, a permanent cure may not result. PMID- 1633374 TI - Psychological interventions for chronic pain following spinal cord injury. AB - Currently, no literature is available regarding the clinical efficacy and treatment outcome of psychological interventions for chronic pain among spinal cord injured (SCI) persons. The present article provides a framework for cognitive-behavioral interventions used with other pain populations and suggested application for the SCI population with chronic pain. Primary focus is upon a biopsychosocial model with patient self-management as the treatment goal. SCI rehabilitation has traditionally relied upon self-management strategies, as have recent psychological treatment approaches for chronic pain. In addition, recommendations for treatment outcome research are provided with the emphasis on using existing standardized assessment and measurement protocols. PMID- 1633376 TI - Pain-specific beliefs, perceived symptom severity, and adjustment to chronic pain. AB - Cognitive theories of appraisal argue for the importance of beliefs as determinants of adjustment to stress. The current investigation sought to examine the relation between beliefs about chronic pain and adjustment in a group of chronic pain patients. Patients' belief in themselves as disabled was found to be inversely related to activity level for patients reporting low and medium levels of pain severity. This same belief correlated with professional services utilization and was negatively related to psychological functioning. Believing in a medical cure for pain was also positively related to professional services utilization. Finally, an expressed belief in the appropriateness of solicitous responses from family members was negatively related to psychological functioning for patients reporting relatively low levels of pain. Although these findings support the broad-based hypothesis that the illness-relevant beliefs of chronic pain patients are associated with their multidimensional pain adjustment, they emphasize the importance of beliefs concerning whether or not one is disabled by pain. The findings also highlight the fact that the belief/functioning relation is not always direct and can be moderated by perceived pain severity. PMID- 1633375 TI - Chronic pain and spinal cord injury: review and comment. AB - The problem of severe chronic pain following spinal cord injury (SCI) has been well delineated for many years. However, progress has been slow in determining which treatment procedures work for which type of SCI pain in a particular individual at a particular time. Reasons for such slow progress include the low incidence and prevalence of SCI making large series of patients unavailable for trials in many centers. Lack of a widely accepted SCI pain classification scheme has also limited the comparability of similar interventions carried out by different investigators. Design limitations of many existing studies that can be remedied in future investigations are reviewed. Finally, discussion of two conceptual models of SCI pain is presented and an argument raised for the utility of both. PMID- 1633377 TI - Living with fibromyalgia. Consequences for everyday life. AB - The influence of chronic pain on daily life was studied in 58 patients (55 women and three men) with fibromyalgia. The mean age was 45 +/- 11 (SD) years. A mail questionnaire including a 2-day diary was used for data collection. Information was gathered on social background, employment status, symptoms, physical training habits, patients' experience of general health, physical condition, and difficulties in performing motor tasks. The patient reported every half hour in the activity diary the degree of pain and fatigue, whether the activities were difficult to perform, and whether the patient considered them to be enjoyable, valuable, and meaningful. Fifty-five percent of the group had gainful employment. Most were working shorter hours and with changed work tasks. Motor tasks, such as carrying, holding, and running were more difficult to perform than before the onset of the symptoms, and half of the group reported most of their activities as strenuous to perform. Thirty-nine persons (67%) reported no, or very short, pain free periods during the 2 days. In conclusion, symptoms influenced daily life considerably, and almost all patients reported changes in habits and routines as a consequence of fibromyalgia. An assessment of the patient's total life situation gives valuable information for understanding the patients' ability to handle everyday life. PMID- 1633378 TI - Postoperative pain relief and hospital stay after total esophagectomy. AB - Intraoperative and postsurgical epidurally administered pain relief is associated with reduced morbidity. We reviewed the charts of 19 patients who had total esophagectomy to see whether the method of postoperative pain relief influenced the length of hospital stay and cost of the procedure. The patients received either intravenous (group M) or epidural (group E) morphine for postoperative pain. The length of stay in the intensive care unit was reduced by 2 1/2 days and total hospital stay by 7 days in the epidural group. This resulted in a saving of Canadian $12,770 per patient. PMID- 1633379 TI - A survey of pain in hospitalized patients aged 4-14 years. AB - One hundred fifty randomly selected hospitalized children between the ages of 4 14 were interviewed to assess their pain experience in the hospital. Follow-up information was obtained through parent interviews 3 weeks, 3 months, and 6 months later. On enrollment, more than 87% of children reported having had pain within 24 h and, of those, 19% reported their usual pain intensity as in the severe range. Thirty-eight percent of children had received analgesic medication during the preceding 24 h. Children who had undergone surgery were three to four times more likely to have received narcotic analgesic than nonsurgical patients, although similar proportions in both groups reported moderate to severe pain intensity. In spite of these reports of significant pain by a substantial number of children during hospitalization, at the 3-week follow-up check, by parent report, 68% were pain free. The parents of those with pain were contacted at 3 and 6 months postenrollment, and 96% of children were no longer experiencing pain. Five children reported pain at all contact points; three of these were suffering chronic diseases and the other two had suffered major trauma from motor vehicle accidents. PMID- 1633380 TI - Chronic pain: fix or manage? PMID- 1633381 TI - Migraine and tension-type headaches: in response to comment by Dr. Campbell. PMID- 1633382 TI - Somatosensory evoked potentials and stellate ganglion block. PMID- 1633383 TI - The needle and the brain: psychophysiological factors involved in nerve blocking for chronic pain. In response to article by Drs. Brena, Chapman, and Sanders. PMID- 1633384 TI - In response to the position paper of the NCAHF on acupuncture. PMID- 1633385 TI - Phantoms and follow-up. PMID- 1633386 TI - Drug abuse, dependence, and addiction in chronic pain patients. AB - It is claimed that a significant percentage of chronic pain patients suffer from drug/alcohol abuse/dependency/addiction. To address this question, 24 articles alluding to chronic pain patient drug/alcohol dependence/addiction were reviewed according to the following criteria: method for drug misuse diagnosis, which drug misuse diagnosis used (abuse, dependence, or addiction), and percentage of patients within each diagnostic category of drug misuse. The result of the review indicated that only seven studies utilized acceptable diagnostic criteria and/or definitions for the drug misuse diagnoses and gave percentages of drug misuse. Within these seven studies, the prevalence percentages for the diagnoses for drug abuse, drug dependence, and drug addiction were in the range of 3.2-18.9%. It is concluded that these diagnoses occur in a significant percentage of chronic pain patients. However, there is little evidence in these studies that addictive behaviors are common within the chronic pain population. PMID- 1633387 TI - Chronic pain and spinal cord injury. AB - With the medical progress that has given spinal cord injured individuals greater longevity and better overall health, chronic pain has emerged as a major challenge in treating this population. Over the past 40 years, estimates of prevalence of severe/disabling chronic pain in spinal cord injury (SCI) patients have ranged from 18% to 63%. Beyond this finding, the extant literature is extremely limited. This review summarizes the empirical findings with regard to the prevalence and clinical significance of chronic pain in the SCI population. In spite of widespread clinical beliefs, there is little evidence that characteristics of the SCI such as the level, completeness, or etiology of the injury are associated with either the development or severity of pain. Until recently, psychosocial issues have been almost totally ignored in spite of the importance such variables have demonstrated in chronic pain in other populations. A major purpose of the present article is to expand the scope of inquiry to include these factors and to emphasize the importance of employing a biopsychosocial model. Evidence is reviewed which suggests that chronic pain is associated with psychosocial impairment in this population. It is concluded that rather than being a minor problem in comparison to the other limitations imposed by SCI, chronic pain represents a significant additional challenge to the SCI patient that may be best addressed by a multidisciplinary approach. PMID- 1633388 TI - Pain assessment in spinal cord injury. AB - Pain management is a serious problem for individuals with spinal cord injury (SCI). Recent developments in pain assessment indicate that multiaxial approaches, assessing medical, psychosocial, and behavioral/functional dimensions, are necessary to measure adequately the impact of chronic pain. The application of this multiaxial system to persons with SCI and chronic pain is presented. A review of the literature indicates that the psychometric properties and test utility for most pain measures have not been established for persons with SCI. The assessment task is further confounded by the functional limitations and psychosocial impairments that may accompany SCI. Recommendations are made for adapting established pain measures for use with SCI individuals. The choice of assessment tools for these patients is guided by the multidimensional nature of the pain experience, functional limitations, and the goals of treatment. PMID- 1633389 TI - Ultrafast MR imaging of water mobility: animal models of altered cerebral perfusion. AB - "Single shot" magnetic resonance (MR) diffusion imaging was used to study the details of signal decay curves in experimental perturbations of cerebral perfusion induced by hypercapnia or death. Despite large perfusion increases observed with dynamic susceptibility-contrast MR imaging, no correlation with these changes was seen in either the diffusion coefficient or any other intravoxel incoherent motion (IVIM) model parameters in dog gray matter as arterial carbon dioxide pressure increased. Non-monoexponential signal decay in cat gray matter was seen both before and after death. In addition, cat gray matter demonstrated a steady decrease in the diffusion coefficient after death. These data are strong evidence that the fast component of the non-monoexponential diffusion-related signal decay is not due solely to perfusion. The authors believe that a second compartment of nonexchanging spins, most likely cerebrospinal fluid, accounts for the non-monoexponential decay. PMID- 1633390 TI - In vivo Na-23 MR imaging and spectroscopy of rat brain during TmDOTP5- infusion. AB - In vivo sodium-23 and hydrogen-1 magnetic resonance (MR) imaging and spectroscopy of the rat brain during infusion of the shift reagent thulium DOTP5- (1,4,7,10 tetraazacyclododecane-1,4,7,10-tetra[methylene phosphonate] was performed to assign the various peaks observed during infusion and to evaluate the shift reagent in discriminating tissue compartments. Na-23 spectra collected during the infusion showed two shifted peaks that were assigned to intravascular Na+ and extracellular muscle Na+, respectively, and one unshifted peak assigned to intra- and extracellular brain Na+ and cerebrospinal fluid Na+. These assignments were validated with H-1 and Na-23 MR imaging and Na-23 chemical shift imaging (CSI). The H-1 and Na-23 images showed that a surface coil placed on a rat head can detect a substantial amount of signal from muscle surrounding the skull. Na-23 CSI spectra from successive 1-mm-thick coronal sections indicated that the shift reagent did not cross the blood-brain barrier. The study also showed that bulk susceptibility shifts are quite small with Tm-DOTP5-. This reagent may be useful in determining compartmental Na+ concentrations and blood flow kinetics in brain and in examining the integrity of the blood-brain barrier. PMID- 1633391 TI - Thin-section MR imaging of rat brain at 4.7 T. AB - The brains of anesthetized 7-month-old male hooded rats were imaged in coronal, sagittal, and horizontal planes at 4.7 T. Images were obtained with a section thickness of 0.6 mm and in-plane pixel size of 0.18-0.20 mm, resulting in finer combined spatial and contrast resolution than in most previously published reports. This allowed detailed anatomic assignment of many brain structures on the basis of comparison with a histologic brain atlas. T1, apparent T2, and water proton density values of gray matter, white matter, and cerebrospinal fluid (CSF) were derived from saturation-recovery and multi-echo measurements. These values were used to calculate expected contrast-to-noise ratios as a function of TR and TE in spin-echo imaging sequences. The optimal simultaneous contrast between gray and white matter and between CSF and gray matter was obtained on images with moderate T2 weighing, with a TR of 3.6 seconds and a TE of 45 msec. The use of thin sections was found to be essential for resolving many fine structures, and the improved sensitivity provided by the high magnetic field strength was crucial for imaging such thin sections at adequate signal-to-noise ratios. PMID- 1633392 TI - Gadolinium-enhanced magnetization transfer contrast imaging of intracranial tumors. AB - The magnetization transfer contrast (MTC) technique was used in low-field strength (0.1 T) magnetic resonance (MR) imaging of 28 patients with intracranial tumors. MTC images were generated with an off-resonance, low-power radio frequency pulse applied during the interpulse delay period of a gradient-echo partial-saturation sequence (TR msec/TE msec = 200/20). Images in the presence and absence of the MTC pulse were concurrently acquired before and after injection of gadopentetate dimeglumine at a dose of 0.1 mmol/kg. The contrast agent enhanced 27 of 28 tumors. Application of the MTC pulse improved the contrast-to-noise ratio (C/N) between tumor and normal white matter in 26 of 28 cases on the preinjection images and in 25 of 28 cases on the postinjection images. On the gadolinium-enhanced images, the mean C/N was 2.6 +/- 1.7 without the MTC pulse and 3.2 +/- 1.9 with the MTC pulse. The greatest contrast improvement with the MTC technique was obtained in tumors showing the strongest paramagnetic enhancement. The results indicate that MTC can improve contrast between normal brain and some intracranial neoplasms. The use of gadopentetate dimeglumine generally intensified this effect. PMID- 1633393 TI - Effect of perfusion on exercised muscle: MR imaging evaluation. AB - An ischemic clamp model of exercise was used to evaluate the potential role of blood flow in mediating changes in the magnetic resonance imaging appearance of skeletal muscle. Proton relaxation times of muscle were serially estimated in 10 healthy subjects (a) before exercise, (b) after exercise in the presence of vascular occlusion (VO1), (c) during vascular reocclusion after 1 minute of reperfusion (VO2), and (d) after reinstitution of continuous flow. T1 and T2 of active muscles were increased during VO1. During VO2, there were additional increases in relaxation times of active muscles. Reinstitution of continuous flow was associated with a continuous decrease in the T2 of exercised muscle. Hence, blood flow was not required for increases in T1 and T2 with exercise. Additional relaxation time increases occurred after a brief period of reperfusion; however, continuous flow was associated with a decrease in T2. PMID- 1633394 TI - Cardiac masses: signal intensity features on spin-echo, gradient-echo, gadolinium enhanced spin-echo, and TurboFLASH images. AB - Fifteen patients with cardiac or paracardiac masses underwent magnetic resonance (MR) imaging with spin-echo (n = 15), cine gradient-echo (n = 15), gadopentetate dimeglumine-enhanced spin-echo (n = 15), and TurboFLASH (fast low-angle shot) (n = 7) sequences. All masses had either histologic confirmation (n = 11) or confirmation with other imaging modalities (n = 4). Myxomas (n = 6) were characterized by an intermediate signal intensity (SI) on spin-echo (n = 6) and low SI on cine gradient-echo (n = 6) images and moderately high-SI contrast enhancement (n = 5). Percent contrast enhancement for myxomas was 57% +/- 11%. Thrombus (n = 4) had intermediate (n = 3) or high (n = 1) SI on spin-echo images and low (n = 2) or intermediate (n = 2) SI on gradient-echo images and did not show substantial contrast enhancement. Postcontrast first-pass TurboFLASH images were useful by clearly demonstrating the nonenhancing mass lesion in a high-SI blood pool. Other cardiac and paracardiac tumors (n = 5) showed variable pre- and postcontrast spin-echo SI; however, no other tumor showed low SI on cine gradient echo images. PMID- 1633395 TI - MR imaging of blood vessels with an intravascular coil. AB - A method for producing high-resolution magnetic resonance (MR) images of blood vessel walls is described. The authors review a theoretical analysis of receiver coil design and present a coil well suited for intravascular MR imaging. The design is based on two coaxial solenoids separated by a gap region and with current driven in opposite directions. Placement of this receiver coil within the vascular space is shown to provide a substantial increase in sensitivity over that external surface coils. Experimental verification of these predictions was obtained in a vessel phantom in which a 13-cm surface coil was compared with a 3.5-mm-diameter opposed-solenoid intravascular coil. This intravascular coil had a cylindric region of high sensitivity that offered a 10-fold improvement in signal-to-noise ratio over that of an external coil near the vessel wall. The performance of this coil was also tested in the jugular vein of a swine. PMID- 1633396 TI - MR angiography with adiabatic flow excitation. AB - A new method of magnetic resonance (MR) angiography is presented that produces signal from flowing spins and suppresses that from stationary spins by means of a flow excitation pulse sequence consisting of adiabatic 90 degrees and 180 degrees radio-frequency (RF) pulses interleaved with flow-dephasing gradient lobes. Stationary spins are refocused along the z axis, while flowing spins are dephased by the gradient lobes and generate a transverse component that can be measured directly to produce the angiogram. Adiabatic RF pulses and unipolar gradient lobes give the pulse sequence a high degree of immunity to RF and magnetic field inhomogeneity. The pulse sequence can be successfully applied with a transmit/receive surface coil. The disadvantage of adiabatic RF pulses is that their long duration makes it difficult to suppress the signal of stationary spins with short T2. PMID- 1633397 TI - High-speed black blood imaging of vessel stenosis in the presence of pulsatile flow. AB - Stenosis phantoms were created to study the ability of "black blood" methods to image a vessel stenosis in the presence of pulsatile flow. Black blood images were acquired with a modified TurboFLASH (fast low-angle shot) method that eliminates flow signal by applying a set of prepulses before segmented data acquisition. With this high-speed approach, imaging can be completed within 16 seconds. This technique was compared with conventional spin-echo black blood, gradient-echo black blood, and gradient-echo bright blood methods. Loss of flow signal, which extended beyond the site of the stenosis, was seen on the gradient echo bright blood images. The pattern of signal loss varied with the type of stenosis. Flow voids were achieved with spin-echo black blood imaging; however, substantial ghosting artifacts were seen. With gradient-echo black blood imaging, it was difficult to eliminate all flow signal, particularly for in-plane flow. The modified TurboFLASH method produced high-quality black blood images in a fraction of the time needed for spin-echo imaging. It showed no ghosting artifacts even in the presence of pulsatile flow. PMID- 1633398 TI - Comparison of velocity-encoded MR imaging and fluid dynamic modeling of steady and disturbed flow. AB - The contrast of flow-encoded magnetic resonance (MR) images obtained in vivo and the accuracy of velocity measurements are complicated by the presence of complex flow states. The effects of complex flow states on MR flow-encoded images were studied and quantitative flow information was obtained with an MR phase subtraction technique. Regions of complex flow, including flow stagnation and separation and laminar flow, could be clearly identified on the phase images. The MR imaging velocity measurements were validated by comparison with numerical simulation results for three-dimensional velocity distributions. The velocity MR images and the profiles obtained from the simulation generally agreed well for flow rates of 660 and 1,680 mL/min. This agreement lends support to both the fluid dynamic model and the physical basis of the phase imaging technique and establishes the validity of flow-encoded phase imaging as an in vivo flow quantitation method, especially under low Reynolds number flow conditions. PMID- 1633399 TI - Mechanisms of flow-induced signal loss in MR angiography. AB - Mechanisms of signal loss in magnetic resonance angiography were studied with a stenotic flow phantom. The results indicate that while signal loss induced by mean fluid motions is localized about the stenosis, the fluctuating component of fluid motion induces signal loss over a much larger region, primarily distal to the stenosis. For both motion components, use of gradient moment nulling (GMN) above first order was found to be an ineffective means of reducing signal loss. In contrast, shortened gradient durations were found to reduce signal loss substantially. However, though a zeroth-order gradient is generally of the shortest duration, use of a slightly longer, first-order gradient was found to be the most robust means of reducing signal loss. PMID- 1633400 TI - Diagnosis of fatty liver with MR imaging. AB - The diagnosis of fatty liver with magnetic resonance (MR) imaging was evaluated in experimental rat models of simple fatty infiltration and fatty liver with hepatocellular injury. T1 and T2 were measured ex vivo and correlated with the histologic degree of fatty infiltration. Enhancement of fatty liver with four different cells-specific contrast agents was studied with ex vivo relaxometry and in vivo MR imaging. Quantitative analysis of conventional and chemical shift MR images was correlated with biochemically determined fat content of the liver. Diet-induced simple fatty infiltration of the liver caused a decrease in T1 of 15%, whereas the T1 of L-ethionine-induced fatty liver with hepatocellular injury increased by 12%. T2 showed a positive correlation with the degree of fatty infiltration in both models. Cell-specific hepatobiliary contrast agents showed the same liver uptake and relaxation enhancement in fatty livers as in normal livers. Conventional T1-weighted images and chemical shift images showed good correlation (r = .83 and .80, respectively) between signal intensity and the degree of fatty infiltration. However, only chemical shift imaging was reliable in the diagnosis of fatty liver. PMID- 1633401 TI - Echo-planar imaging of the central nervous system at 1.0 T. AB - Echo-planar imaging (EPI) on the authors' 1-T prototype imager provides high quality 100-msec images of the central nervous system. Contrast parameters can be chosen freely. Three-dimensional EPI sequences provide isotropically resolved data sets with 1-mm resolution. Brain perfusion and blood-brain barrier disruption can be assessed in time-course studies with gadopentetate dimeglumine. The current state of development of the authors' midfield research EPI system is discussed and its image quality illustrated through selected patient studies. PMID- 1633402 TI - Incremental hydraulic jaw opener for MR imaging of the temporomandibular joint. AB - Magnetic resonance (MR) imaging in the open- and closed-mouth positions is the method of choice for visualizing the temporomandibular joint (TMJ). To analyze the TMJ in response to various degrees of mouth opening, the authors constructed a hydraulic incremental jaw opener. This apparatus enables obtaining of reproducible and stable positions of TMJ articulation. With modified gradient pulse sequences, the technique yields good spatial resolution of joint anatomy, including that of the articular disk. The application of a cine program allows cinematographic display of TMJ motion, which in conjunction with static open- and closed-mouth views can be useful in the diagnosis of TMJ dysfunction. The authors used the incremental jaw opener to examine the disk-condyle complex at each open mouth position, with particular attention to extreme open-mouth positions. PMID- 1633403 TI - Fast spin-echo studies of contrast and small-lesion definition in a liver metastasis phantom. AB - A liver-metastasis model was used to study the ability of fast spin-echo (FSE) imaging to show small lesions (1 pixel in diameter) relative to conventional spin echo imaging. FSE images of the liver-metastasis phantom were acquired with various phase-encode reordering schemes to manipulate T2 contrast. The imaging time for multisection acquisitions was 27 seconds for FSE imaging and 6 minutes 48 seconds for conventional spin-echo imaging. Computer simulations were performed to determine how the point spread function varies with the different phase-encoding orders in FSE imaging. Contrast-to-noise ratios and signal profiles of the lesions were measured as a function of the effective TE and lesion size. Experimental results and theoretical simulations showed that T2 weighted FSE imaging provides high contrast and good edge definition even for small lesions. The results indicate that FSE imaging may become a powerful method for the early detection of liver metastases. PMID- 1633404 TI - Why we should speak out for restriction of handguns. PMID- 1633405 TI - Developmental expression of estrogen receptor mRNA in the rat cerebral cortex: a nonisotopic in situ hybridization histochemistry study. AB - The distribution of estrogen receptor mRNA expression was studied in the developing rat cerebral cortex by in situ hybridization histochemistry. We used a specific, nonisotopically (digoxigenin) labeled, synthetic oligodeoxyribonucleotide complementary to a 48 base sequence in the region of the estrogen-binding domain of rat uterine estrogen receptor cDNA. During development, estrogen receptor mRNA was observed in all forebrain regions previously reported to bind estrogen, as determined by steroid autoradiography or nuclear binding assay. In the developing cerebral cortex, estrogen receptor mRNA was extensively expressed in the ventricular zone, primitive plexiform layer, and immature cortical plate at least as early as embryonic day 16. During the first 3 postnatal weeks, cortical mRNA expression was increasingly restricted to the upper third of the cerebral cortex and to the neurons of the cortical subplate (layer VIb/VII) and decreased to low levels by postnatal day 28. In the cerebral cortex, the spatial distribution of estrogen receptor mRNA expression overlapped that reported for the encoded protein. The extensive distribution of estrogen receptor mRNA throughout the late prenatal and early postnatal cerebral cortex points to an important role for estrogen in the differentiation and maturation of the cerebral cortex. PMID- 1633407 TI - Cholinergic immunoreactive fibers in monkey anterior temporal cortex. AB - Cholinergic processes in anterior temporal cortex of rhesus monkeys were identified using immunocytochemical techniques for ChAT. Labeled fibers were present throughout the temporal pole and anterior aspects of the superior temporal, middle temporal, and inferior temporal gyri. ChAT-immunoreactive fibers were most dense in layer I to superficial layer III throughout anterior temporal cortex. In temporal pole, agranular and dysgranular regions had a greater density of labeled fibers in superficial layers as compared to granular regions. In addition to the superficial concentration of cholinergic fibers in lateral temporal regions, numerous labeled fibers were also present in deep cortical layers in the inferior temporal gyrus of lateral temporal cortex, with lesser concentrations of immunoreactive fibers present in these layers in superior and middle temporal gyri. These patterns of cholinergic innervation may reflect the degree of cholinergic modulation of functions in anterior temporal cortex. PMID- 1633406 TI - Early expression of GABA-containing neurons in the prefrontal and visual cortices of rhesus monkeys. AB - Light and electron microscopic immunohistochemistry was used to examine the time of emergence and distribution of GABA-containing cells in an association (prefrontal) and primary sensory (visual) region of the telencephalon at progressive fetal and postnatal stages of cortical maturation in the rhesus monkey. Thirty fetuses and six postnatal monkeys were examined beginning at embryonic day 41 (E41), the start of cortical neurogenesis, to birth (E165) and proceeding to maturity (greater than 5 years of age). The emergence and major developmental modifications in the distribution of immunoreactive neurons in both areas examined were nearly identical. GABA-immunolabeled neurons were present throughout the full thickness of the cerebral wall, including the cortical plate and the developmentally transient marginal, subplate, and ventricular zones, as early as E41. An important and surprising result was that a subset of bipolar migrating neurons in the subplate zone also contained GABA at these early stages. GABA-containing neurons in the ventricular and subventricular zones disappeared after E100, when neurogenesis is completed. In contrast, the number of immunoreactive multipolar and bipolar neurons within the subplate zone diminished between E100 and E131. By the first postnatal week, the distribution and density of GABA-containing neurons in the cortex appeared qualitatively similar to that observed in mature monkeys. The early appearance of GABA in cortical neurons and its expression by a population of migrating neurons suggest that a subset of cortical neurons may be committed to a transmitter phenotype independent of synaptic interactions and prior to attaining their adult positions in the maturing cerebral cortex. PMID- 1633408 TI - Nonphosphorylated neurofilament protein and calbindin immunoreactivity in layer III pyramidal neurons of human neocortex. AB - Subpopulations of pyramidal neurons in the neocortex have been shown to contain nonphosphorylated neurofilament protein (NPNFP) and calbindin D28K (Morrison et al., 1987; Campbell and Morrison, 1989; Hof et al., 1990; Kobayashi et al., 1990; Hof and Morrison, 1991; Mesulam and Geula, 1991). However, it is not known what relations, if any, exist between the pyramidal neurons containing each of these proteins. In this study, the expression of NPNFP and calbindin immunoreactivity was compared in six regions of human neocortex. Characteristic laminar patterns of immunoreactivity for each protein were seen in most regions examined, and both NPNFP- and calbindin-labeled pyramidal neurons were found in layer III. However, the pyramidal neurons labeled with NPNFP and calbindin differed in several respects. First, the sublaminar distribution of NPNFP-labeled pyramids within layer III differed across regions, ranging from an even distribution throughout the layer in a visual association region (area 18) to a predominance of labeled neurons in the deep half of that layer in a higher association region (area 20). The distribution of calbindin-immunoreactive pyramidal neurons also varied regionally, but in a different manner than that of the NPNFP-labeled neurons. Second, in every region examined, the average size of NPNFP-labeled layer III pyramids was greater than that of calbindin-immunoreactive pyramids. However, there was substantial regional heterogeneity in the extent to which the size distributions of neurons in each of the two populations overlapped. Third, in the regions in which NPNFP- and calbindin-immunoreactive neurons were most similar in size, the amount of colocalization (as identified by double-labeling studies) was also greatest. Similarly, in the regions in which there was minimal overlap in the size of the NPNFP- and the calbindin-immunoreactive neurons, there was minimal colocalization. These regional characteristics of NPNFP- and calbindin immunoreactive layer III pyramidal neurons have implications for the involvement of these neuronal populations in Alzheimer's disease. PMID- 1633409 TI - Positron emission tomography study of letter and object processing: empirical findings and methodological considerations. AB - The study of functional-anatomical correlations of higher-order cognitive processing has benefited from recent advances in brain imaging techniques such as positron emission tomography (PET) measurements of regional cerebral blood flow (CBF). Comparisons of CBF changes by paired image subtraction provide the opportunity to isolate cerebral areas participating in the realization of the processes that differentiate two tasks. However, the subtraction method is based on assumptions that are not entirely compatible with cerebral cognitive processing, and the derived pattern of activation specifically associated with the processes that differentiate two tasks is relative to the activation associated with the subtracted task and may therefore vary as a function of the processes actually performed in this subtracted task. To examine the implications of this procedure, a PET study with the 15O water bolus technique was carried out on normal adults. Subjects performed three tasks that made nonoverlapping cognitive processing demands: a semantic categorization of visual objects, a spatial discrimination of visually presented letters, and a phonological decision on visually presented single letters. Each task produced distinct patterns of activation consistent with evidence from neurological patients, specifically in the left occipital cortex in the semantic categorization of objects, in the parietal cortex of both hemispheres in the letter-spatial task, and in the left frontal and superior temporal cortex in the letter-sound task. However, the comparisons between the two letter tasks did not result in the expected CBF changes even though these two tasks make distinct processing requirements and are dissociable by brain injury. In addition, the phonological task resulted in activation of areas of the frontal cortex that earlier PET studies had identified as participating in semantic operations, whereas letters have no semantic property. These results suggest that the interpretation of patterns of activation is confronted with difficulties due to the automatic, and uncontrolled, processing of verbal stimuli that raises the threshold for significant CBF changes between two conditions that use the same stimuli but different task demands. PMID- 1633410 TI - Mechanisms underlying somatosensory cortical dynamics: II. In vitro studies. AB - The response of the sensorimotor cortical slice to repetitive, single-site afferent drive is mapped using both evoked potential and metabolic mapping [2 deoxyglucose (2DG)] methods. Systematic changes (increases or decreases) in the evoked potential occur during repetitive 3-5 Hz stimulation. These resemble the changes in SI neuron response observed in the in vivo studies of the preceding companion article; they occur rapidly, recover within 1 min and are reproducible if stimulus parameters remain unchanged. Place, timing, and intensity of repetitive stimulation influence the amplitude and form of the response alterations observed at a given cortical locus. The neuron populations that exhibit different response modifications to the same repetitive stimulus are distributed nonrandomly in the slice: neurons occupying column-shaped aggregates undergo a common response alteration (either an increase or decrease) during repetitive stimulation, with sharp boundaries separating neighboring aggregates distinguishable on the basis of their dynamic behaviors. The distribution of stimulus-evoked 2DG uptake in the slice is "columnar," the dimensions of the 2DG columns corresponding to those mapped with neurophysiological methods. Taken together, the findings support the concept that repetitive stimulation causes the intrinsic network of somatosensory cortex to modify dynamically the network's response to extrinsic excitatory drive so that the local differences in the pattern of extrinsic excitatory drive to neighboring cortical columns are enhanced. PMID- 1633412 TI - Immediate and delayed changes of rat motor cortical output representation with new forelimb configurations. AB - These experiments examined motor cortical representation patterns after forelimb postural adjustments in rats. The experiments tested the hypothesis that postural adjustments that stretch muscles that are most strongly activated from the primary motor cortex (MI) enlarge their cortical representation. Intracortical electrical stimulation within MI, forelimb muscle activity and movements, and vibrissa movements were used to evaluate the border between the MI forelimb and vibrissa representations before and after forelimb position changes in anesthetized adult rats. The forelimb was originally maintained in retraction (wrist extension and elbow flexion) and then changed to protraction (wrist flexion and elbow extension). Movements and forelimb EMG evoked by electrical stimulation were evaluated during this period (up to 3 hr) through a set of four electrodes implanted in layer V of MI. Changing the forelimb configuration had both immediate and delayed effects on forelimb muscle activity evoked from MI. At some sites, the magnitude of evoked forelimb muscle activity immediately increased with forelimb protraction. At one-quarter of all sites, forelimb muscle activity was evoked where it was not previously detected following an average delay of 22-31 min after forelimb protraction. This change can be interpreted as an expansion of the forelimb area into the vibrissa representation. These data further support the hypothesis that motor cortical representations are flexible and show that sustained changes in somatic sensory input to MI are sufficient to reorganize MI output. PMID- 1633411 TI - Effects of continuous noise maskers on tone-evoked potentials in cat primary auditory cortex. AB - In nine barbiturate-anesthetized cats, cortical evoked potentials for tones presented to the contralateral ear were studied for the effects of continuous wideband noise masking. In five animals, input-output functions for tones were obtained in the presence of continuous noise masking at the same ear. Tone thresholds were raised by the presence of the masker, and they closely tracked the level of the masker, such that increments in masker level brought about tone threshold elevations of the same magnitude. In four animals, we compared the effect on responses to contralateral tones of continuous maskers presented to the same ear as the tone, to the opposite ear, and to both ears simultaneously. The presence of the masker at the ear opposite the tone had a small and variable effect on the response to the stimulus at the ear with the tone, whether or not noise was also present at that ear. Consideration of extant single-neuron evidence provides an interpretation of these findings. Whereas maskers at the ear with the tone are known to reduce signal sensitivity for almost all cortical neurons, the effects of masking at the ear opposite the tone (ipsilateral to the cortex) are likely to be very heterogeneous. It is likely that the perceptual salience of signals that have different binaural configurations to concurrent maskers resides in which neuronal elements are activated, rather than in the total number of cells excited, and it is perhaps for this reason that the evoked potentials show only modest effects of this masking parameter. PMID- 1633413 TI - A cortico-subcortical model for generation of spatially accurate sequential saccades. AB - This article provides a systems framework for the analysis of cortical and subcortical interactions in the control of saccadic eye movements, A major thesis of this model is that a topography of saccade direction and amplitude is preserved through multiple projections between brain regions until they are finally transformed into a temporal pattern of activity that drives the eyes to the target. The control of voluntary saccades to visual and remembered targets is modeled in terms of interactions between posterior parietal cortex, frontal eye fields, the basal ganglia (caudate and substantia nigra), superior colliculus, mediodorsal thalamus, and the saccade generator of the brainstem. Interactions include the modulation of eye movement motor error maps by topographic inhibitory projections, dynamic remapping of spatial target representations in saccade motor error maps, and sustained neural activity that embodies spatial memory. Models of these mechanisms implemented in our Neural Simulation Language simulate behavior and neural activity described in the literature, and suggest new experiments. PMID- 1633414 TI - 1992 Krieg Cortical Kudos Awards presented at the Cajal Club. PMID- 1633415 TI - Cortical Discoverer Award: Jennifer Lund, Department of Anatomy and Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania. PMID- 1633416 TI - Cortical Explorer Award: Sharon Juliano, Department of Anatomy, Uniformed Services University of the Health Sciences, Bethesda, Maryland. PMID- 1633417 TI - Cortical Scholar Award: Christopher Muly, Department of Neurobiology, Duke University Medical Center, Durham, North Carolina. PMID- 1633419 TI - Oncogenes and cell proliferation. PMID- 1633420 TI - Regulation of p21ras by GTPase activating proteins and guanine nucleotide exchange proteins. AB - Ras proteins play a critical role in controlling normal cellular growth and, when activated by mutation, in causing malignant transformation. Regulation of p21ras is achieved by GTPase activating proteins, which control the rate of hydrolysis of GTP to GDP, and also by GDP dissociation stimulators, which catalyze the exchange of guanine nucleotides. Several such proteins have now been identified and their control mechanisms characterized. PMID- 1633421 TI - Viral genetics. PMID- 1633418 TI - Mechanisms underlying somatosensory cortical dynamics: I. In vivo studies. AB - The experiments of this study demonstrate that relatively modest rates of repetitive tactile stimulation are accompanied by rapid and reversible modifications (either increases or decreases) in the response of SI neurons. Complete recovery occurs in a few minutes following cessation of stimulation. The modifications are reproducible (1) if stimulus parameters remain the same and (2) if time for recovery is provided between successive exposures. In contrast, repetitive tactile stimuli identical to those that modify SI neuron response rarely lead to changes in the response of cutaneous mechanoreceptive afferents. SI neuron functional properties conventionally regarded as immutable [e.g., directional selectivity, and distribution of sensitivity within the receptive field (RF)] also modify with repetitive stimulation. While the changes in RF organization differ in detail from one neuron to the next, they are similar in form: the response generated by stimulus contact with one (or more rarely, several) RF region(s) becomes enhanced relative to the response the same stimulus evokes from neighboring regions. Neurons in the same column (sampled in the same radial penetration) exhibit very similar changes in the distribution of sensitivity within the RF, whereas neurons sampled in tangential penetrations exhibit diverse, apparently unrelated changes in RF organization in response to the same repetitive stimulus. Simultaneous multichannel recordings reveal that a repetitive tactile stimulus exerts similar effects on the response and RFs of the neurons within local (no more than 100 microns) neuron groupings. A model that incorporates a manner of SI topographical organization (segregate organization) and well-known aspects of neocortical cellular, neurotransmitter/receptor, and connectional architecture accounts for the changes in SI neuron behavior observed during repetitive stimulation. PMID- 1633422 TI - Crossed signals: oncogenic transcription factors. AB - Transcription factors operate at key regulatory junctions in the cell's responses to diverse extracellular stimuli. We discuss how the transforming activity of mutated transcription factors encoded by several oncogenes (v-erbA, v-fos, v-jun and v-rel) may result in part from a loss of the integrated response to the signalling network. PMID- 1633423 TI - Negative regulators of growth. AB - The proliferation of cells is regulated by countervailing positively- and negatively-acting signaling networks. The anti-proliferative signals, the study of which has been much neglected until recently, are often conveyed by growth inhibitory peptides. Elements that mediate the cellular response to growth inhibitors are encoded by tumor suppressor genes that if lost may lead to the runaway growth of the cancer cell. PMID- 1633424 TI - Proto-oncogenes in mammalian development. AB - The phenotypic analysis of mice carrying germline mutations in protooncogenes is beginning to provide convincing genetic evidence for the important role that these genes play in mammalian development and differentiation. Two approaches are being taken to elucidate the biological function of proto-oncogenes in vivo. The first involves the molecular analysis of existing mouse developmental mutants, while the second approach involves the generation of specific germline mutations by gene targeting using homologous recombination in embryonic stem cells. Several key points have already emerged from these genetic approaches. First, many proto oncogenes are important to more than one cell lineage and function both during embryogenesis and in the adult. Second, the patterns of expression of these genes provide only a guide to their biological function. Third, mutant phenotypes are generally less severe than would be expected from their expression patterns, suggesting that there may be functional overlap between two or more members of a gene family. PMID- 1633425 TI - Tyrosine kinases and their interactions with signalling proteins. AB - Recent progress has been made in identifying signal transduction pathways controlled by receptor protein-tyrosine kinases. The receptors for nerve growth factor and hepatocyte growth factor have been identified as the Trk and Met tyrosine kinases. The stimulation of intracellular signal transduction pathways by activated receptors appears to involve the association of SH2-containing cytoplasmic signalling proteins with autophosphorylated receptors. PMID- 1633427 TI - Inherited cancer genes. AB - The identification of several genes associated with inherited cancer syndromes has opened a door to understanding mechanisms of carcinogenesis in common, non inherited forms of cancer. Each of these genes appears to play a role in the control of cell growth and differentiation. PMID- 1633426 TI - Learning about cancer genes through invertebrate genetics. AB - Genetic studies in yeast, nematodes and Drosophila are revealing the signal transduction pathways that regulate differentiation and cell proliferation. Some of the critical molecules involved are homologous to proto-oncogenes and others are likely to be analogous to the products of tumor suppressor genes. PMID- 1633428 TI - Genetic variation and quasi-species. AB - During the past year the relative fitness, that is, overall replication ability, and the fitness gain of animal virus variants have been quantified, providing new insight into the dynamics for the generation of RNA virus quasi-species. Measurements of mutant frequencies and rates of genetic diversification have confirmed the extreme complexity of RNA virus and retrovirus populations. PMID- 1633429 TI - Genetic analysis of influenza virus. AB - The newly developed ribonucleoprotein reconstitution and transfection systems have facilitated the characterization of cis and trans functions required for transcription and replication of the influenza virus genome. For the first time, the genome of a negative-strand RNA virus can be manipulated using recombinant DNA techniques. PMID- 1633430 TI - Genetic analysis and gene expression of human immunodeficiency virus. AB - Ten years after the initial description of acquired immune deficiency syndrome, its causative agent, the human immunodeficiency virus, remains the subject of intense scientific interest. Recent research has focused on the detailed analysis of the molecular principles governing gene expression and virion formation and on the cause of immune system dysfunction. Within the past year, considerable progress has been made regarding both the role of the regulatory proteins and the mechanism by which they function, and the determinants of cell tropism and of virion formation. PMID- 1633431 TI - Transcriptional and translational control of gene expression in cauliflower mosaic virus. AB - Cauliflower mosaic virus sequences have developed as a powerful tool for the study of various aspects of gene expression in plants. Analysis of the promoter/enhancer region has led to the discovery of several transcription factors and factor-binding sites. Studies on RNA processing and polyadenylation reveal a viral strategy to obtain terminal redundancy of retrovirus pregenomic RNA. Striking differences between plant and vertebrate polyadenylation signals have been disclosed. The mechanisms for translation of the polycistronic 35S RNA are novel in the eukaryotic field and may give new insight to translational control in general. PMID- 1633432 TI - Differential effects of the novel antidepressant tianeptine on L-5 hydroxytryptophan (5-HTP)-elicited corticosterone release and body weight loss. AB - Biochemical and behavioural experiments have indicated that the novel antidepressant tianeptine stimulates 5-hydroxytryptamine (5-HT) reuptake. The present study has explored the influence of acute tianeptine pretreatment upon corticosterone release and body weight loss following L-5-hydroxytryptophan (5 HTP) administration in conscious rats. Administration of 5-HTP (20 mg/kg i.v.) increased plasma corticosterone levels to a similar extent in rats pretreated either with saline or tianeptine (10 mg/kg i.p., 60 min beforehand). Besides, prior administration of benserazide (50 mg/kg i.p., 30 min beforehand), an inhibitor of peripheral aromatic L-amino acid decarboxylase, prevented 5-HTP induced corticosterone release in both saline- and tianeptine-pretreated rats. However, combined administration of benserazide and 5-HTP decreased overnight body weight in saline-, but not in tianeptine-pretreated rats. These results suggest that tianeptine preferentially activates 5-HT reuptake in central serotonergic neurones. PMID- 1633433 TI - Double-blind cross-over study of phosphatidylserine vs. placebo in patients with early dementia of the Alzheimer type. AB - Thirty-three patients with mild primary degenerative dementia according to DSM III (MMS between 15 and 27) took part in a double-blind cross-over study of phosphatidylserine (Fidia, 300 mg/d) versus placebo. Both treatment phases lasted for 8 weeks with an 8 week washout phase in between and a 4 week washout phase before treatment phase one. Clinical global improvement ratings showed significantly more patients improving under BC-PS than under placebo during treatment phase one. The improvement carried over to the following wash-out and treatment phases. There were no significant improvements in GBS dementia rating scale, psychometric tests or P300-latency. 16-channel EEG mapping findings indicated that the patients initially showed higher power values in all frequency bands (except alpha), when compared to a younger, healthy control group. BC-PS reduced the higher power values compared to placebo, shifting EEG power more towards the normal level. PMID- 1633434 TI - Adding lithium to antidepressant therapy: factors related to therapeutic potentiation. AB - Lithium augmentation of antidepressant drugs was studied in 51 patients with endogenous refractory depression. The remission after 28 days of lithium was obtained in 28 patients (55%). Better effect of lithium was shown in bipolar than unipolar patients, with subjects with lower pre-lithium severity of depression and in those with rapid improvement (within 7 days) on lithium addition. Factors such as age, gender, number of prior antidepressant (or ECT) treatments, type of preceding antidepressant, mean plasma lithium concentration and the results of DST did not show any association with the outcome of lithium augmentation. The 'priming' effect of lithium may contribute to the mechanism of lithium potentiation in a proportion of depressed patients. PMID- 1633435 TI - The human skeletal alpha-actin gene is regulated by a muscle-specific enhancer that binds three nuclear factors. AB - The tissue-specific distal promoter of the human skeletal alpha-actin gene (-1282 to -708) induces transcription in myogenic cells approximately 10-fold and, with the most proximal promoter domain (-153 to -87), it synergistically increases transcription 100-fold (Muscat and Kedes 1987). We report here that it is a short fragment of the distal promoter, the distal regulatory element (DRE) from -1282 to -1177 that functions as a muscle-specific, composite enhancer. An internal deletion in the DRE (delta -1282/-1151) in the context of the full-length 2000 bp promoter, resulted in a 10-fold reduction in transcription. Three distinct nuclear proteins, DRF-1, DRF-2, and DRF-3, interact specifically with the DRE between positions -1260 and -1193. A site specific mutation that abolishes DRF-2 binding also results in a 10-fold reduction in transcriptional activity. The DRF 2 nuclear protein has characteristics similar to those of the muscle-specific regulatory factor, MEF-2 (Buskin and Hauschka 1989; Gossett et al., 1989). Like the MEF-2 binding site in the muscle creatine kinase enhancer, the critical DRF-2 binding site is also an A/T-rich sequence element. The DRF-2 nuclear protein binds equally well to the MCK MEF-2 binding site and to the A/T-rich regulatory element of the skeletal muscle fast-twitch troponin C gene (Gahlmann and Kedes 1990). Furthermore, this troponin C site competes in vivo for DRF-2 driven expression of the skeletal alpha-actin gene in C2 cells. The DRF-2 site alone, however, does not activate transcription in muscle cells when linked to the SV40 promoter. We conclude that the DRF-2 binding element is a MEF-2 binding site that is required but insufficient for regulation of muscle-specific skeletal alpha actin gene expression by the DRE. Thus, muscle-specific regulation of the human skeletal alpha-actin gene appears to require interactions between the other elements of the composite DRE enhancer with the protein:DNA complex formed by DRF 2. PMID- 1633436 TI - Mechanism of tissue-specific transcription: interplay between positive and negative regulatory factors. AB - At least four regulatory cis-acting DNA sequences, CCAAAAGTGG (element A), TTATTTTTA (element B), TATTTATT (element C), and TATTACCTTTAT (element S), were identified in cardiac myosin light chain-2 (MLC2) proximal promoter as target sites for sequence-specific binding of nuclear proteins. For muscle-specific transcription, the proximal promoter (-53 to +1) consisting only of elements B and C is required. Addition of element A to this promoter results in a muscle specific up-regulation, whereas the addition of element S exerts a negative effect on transcription. The negative and positive regulatory effects of elements S and A respectively were demonstrated by site-specific mutations of the promoter following transient transfection of cardiac muscle cells in culture. Elements S and A interact separately with distinct nuclear protein factor present in both muscle and non-muscle cells, even though their regulatory activities are restricted to muscle cells. Among the multiple complexes resulting from the interaction of nuclear proteins and elements S and A DNAs, one requires both S and A sequences together for binding. Element B, which exerts a muscle-specific positive effect on transcription, binds to a nuclear protein present in cardiac muscle, but not in non-muscle cells. DNA-protein binding assays and mutational analysis of the MLC2 promoter suggest that the contribution of the functionally opposed cis-elements depends upon an interplay between the positively and negatively acting DNA-binding proteins via protein-protein interactions to mediate opposite regulatory effects on gene transcription. PMID- 1633437 TI - Detecting interactions between eukaryotic proteins in bacteria. AB - Few convenient genetic assays are available to study protein-protein interactions. This report describes a genetic scheme in E. coli to detect protein protein interactions based on the concept of cooperative DNA binding of two interacting proteins. The yeast regulatory proteins GAL4 and GAL80, which are known to interact with each other, were used to test the scheme. A fusion protein, LexA-GAL80, was found to exert a cooperative effect on the DNA-binding activity of GAL4 as monitored by a bacterial repression assay. PMID- 1633438 TI - Differential protein-DNA interactions at the promoter and enhancer regions of developmentally regulated U4 snRNA genes. AB - In the chicken genome there are two closely-linked genes, U4B and U4X, that code for different sequence variants of U4 small nuclear RNA (snRNA). Both genes are expressed with nearly equal efficiency in the early embryo, but U4X gene expression is specifically down-regulated relative to U4B as development proceeds. At the present time, little is known about the mechanisms that regulate differential expression of snRNA genes. We have now identified a novel chicken factor, PPBF, that binds sequence-specifically in vitro to the proximal regulatory region of the U4X gene, but not to the proximal region of the U4B gene. PPBF is itself regulated during development and may therefore be a key factor involved in differentially regulating U4X gene transcription relative to U4B. The U4X and U4B enhancers contain distinct sequence variants of two essential motifs (octamer and SPH). The Oct-1 transcription factor binds with similar affinities to both the U4X and U4B octamer motifs. However, a second essential snRNA enhancer-binding protein, SBF, has a 20- to 30-fold lower affinity for the SPH motif in the U4X enhancer than for the homologous SPH motif in the U4B enhancer. A potential role therefore exists for SBF, as well as PPBF, in the preferential down-regulation of the U4X RNA gene during chicken development. PMID- 1633440 TI - Histone 3' ends: essential and regulatory functions. PMID- 1633439 TI - The basic RNA polymerase II transcriptional machinery. AB - All genes encoding proteins in eukaryotes are transcribed by RNA polymerase II. The first step in analyzing transcriptional regulation requires understanding the general mechanisms of RNA polymerase II-specific gene transcription. The basal promoter, a template containing a TATA box devoid of upstream regulatory sequences, has been used to identify and characterize the factors which, together with RNA polymerase II, govern transcription in mammalian systems: TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIG, TFIIH, and TFIIJ. Interactions between regulatory transcription factors and basal elements of the transcriptional machinery affect the transcriptional rate in a positive or negative fashion. As these multiple proteins are purified, and their coding sequences are isolated, we come closer to reproducing these processes in vitro with pure components, and thus to elucidating the complex interactions among them. PMID- 1633442 TI - Stereotactic radiosurgery. PMID- 1633441 TI - Identification of three mammalian proteins that bind to the yeast TATA box protein TFIID. AB - The TATA box binding transcription factor TFIID of S. cerevisiae was used as a ligand for affinity chromatography. Polypeptides that bind specifically to yeast TFIID (TFIID-associated proteins, DAPs) were purified from human HeLa (heDAPs) and calf thymus (ctDAPs) whole cell extracts. Both heDAP and ctDAP fractions altered the binding of TFIID to the TATA element, and substituted for the TFIIA transcription activity in a reconstituted in vitro system. The heDAP fraction also behaved like TFIIA in its ability to form a promoter-TFIID-TFIIA complex and to recruit TFIIB to such a complex. The interaction of DAPs with TFIID can confer heat-resistance (47 degrees C) on recombinant yeast or human TFIID. SDS-PAGE analysis revealed that three polypeptides from HeLa extracts specifically bound to yTFIID columns (heDAP35, heDAP21, and heDAP12). These data suggest that a multi-subunit transcription factor with the properties of TFIIA can bind to TFIID in the absence of DNA. PMID- 1633443 TI - Radiation physics for particle beam radiosurgery. AB - For the particles and energies considered suitable for radiosurgery, with increasing particle charge, the Bragg peak height reaches a maximum with helium and then decreases, the Bragg peak width narrows, the distal fall-off steepens, and the exit dose increases (Table 1). The helium-ion beam is superior to a proton beam because of the higher peak-plateau ratio, more rapid dose fall-off, and smaller beam deflection, and it suffers only in the modest exit dose. Comparison of the therapeutically useful parameters of these beams is complicated by the change in beam quality (LET) with depth. Considerations of RBE values, which change with the ion species and with depth of penetration, may alter the relative rankings based on one or more of these beam characterization values. For all these beams, the RBE increases with increasing LET. The effect for protons is small and occurs just at the end of range of the particles. Effective isodose distributions based on modeled beams have been reported for helium, carbon, and neon ions. These distributions include the effects of a varying RBE with changes in the beam quality (as measured by a dose-weighted LET) and the change in dose fraction size with depth (the dose per fraction is a function of the depth of penetration). These calculations suggest that the optimal charged-particle beam for radiosurgery might be carbon. Heavy charged-particle beams can produce dose distributions superior to those obtainable with photon or electron beams. In clinical trials, these dose distributions have proved to be useful for the treatment of human diseases, including neoplasia and life-threatening intracranial disorders.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1633444 TI - Linear accelerator radiosurgery at the University of Florida. AB - The University of Florida radiosurgical project began in 1986 with the following design criteria: the most accurate radiosurgical device possible, state-of-the art computer hardware and software for dose planning, and a number of collimators sufficient to treat any lesion homogeneously. In this article we have reviewed how these goals have been met. Physical aspects of this device (accuracy, dose gradient, and dose-planning speed) as well as clinical results compare favorably with any other radiosurgical experience. We believe that LINAC radiosurgical systems are advantageous in terms of cost, variety of collimator sizes available, and currently available sophistication of computerized dose planning. In the near future, the development of conformal treatment may significantly change the entire field of radiosurgery by offering heretofore unobtainable dose plans for irregularly shaped lesions. In addition, LINAC systems may be adapted for stereotactically focused fractionated radiation therapy and for radiosurgical treatment of lesions elsewhere in the body. Accuracy and computer sophistication notwithstanding, we cannot emphasize strongly enough our belief that the least important determinant of radiosurgical results is the machine used to deliver the radiation. It is absolutely vital that all groups undertaking radiosurgery include neurosurgeons, radiation physicists, and radiation therapists who have spent considerable time studying and learning the myriad details necessary to produce consistently good results. All radiosurgical patients must be followed up carefully and studied so that we can learn how to better apply this technique. Only patients who are not candidates for conventional surgery should be treated radiosurgically, at least until much more is known about long-term success and complication rates. A patient never should be treated radiosurgically simply because the referring or treating neurosurgeon is uncomfortable with proven conventional procedures. All groups performing radiosurgery should strive to adhere to the highest possible standards. We are all responsible for verifying the adequacy of our radiosurgical systems. We are all responsible for selecting our patients well, treating them with a team approach that applies the latest available knowledge of our field, following up closely, and reporting our results honestly and thoroughly so that all can benefit. We owe this, at least, to our patients and to neurosurgery. PMID- 1633445 TI - Radiosurgery using a modified linear accelerator. AB - Stereotactic radiosurgery using modified LINACs is a powerful new technique that offers a versatile method for administering high-dose radiation in a single session. Treatment-planning techniques currently in use enable individual isocenter field shaping, three-dimensional optimization of isocenter placement (including the use of multiple isocenters), and real-time analysis of isodose distribution in three dimensions relative to specifically defined anatomic structures from MR imaging or CT data. Modified linear accelerators offer successful control of both arteriovenous malformations and benign tumors (acoustic neuromas, craniopharyngiomas, and meningiomas), with results equal to the best series reported by users of the gamma knife or heavy-particle systems. More recent work indicates that radiosurgery may play an important role in controlling recurrent pediatric malignant tumors, metastatic cerebral lesions, and even malignant astrocytomas in some patients. Improved correlation of isodose distributions with imaging data allows for sophisticated analysis of results and specific complications, ultimately enabling improved patient care using this exciting new technique. PMID- 1633446 TI - Stereotactic radiosurgery for acoustic tumors. AB - Stereotactic radiosurgery is an important alternative treatment for carefully selected patients with acoustic tumors. We perform radiosurgery under local anesthesia, and 91% of our patients have been discharged from the hospital within 24 hours after treatment. All returned to their preoperative level of function or employment within 5 to 7 days after treatment. Our current tumor control rate is 97%, but reduction in tumor size, judged by strict, objective criteria, was achieved in only 23%. Our actuarial rate of useful hearing preservation after radiosurgery is 38% at 1 year. Three tumors increased in size after treatment. Only one of the three demonstrated increased mass effect on surrounding brain structures by neuroimaging criteria. No increase has led to worsened clinical symptoms or has required surgical excision at this point in follow-up. The 1-year rates for developing new facial or trigeminal neuropathies after radiosurgery were 30% and 33%, respectively. Cranial neuropathies had a delayed onset, with the median onset occurring after 5 to 6 months. The vast majority were partial at onset, and most improved over time. Communicating hydrocephalus requiring ventriculoperitoneal shunts developed after radiosurgery in four patients. Eight patients developed increased signal within adjacent brain parenchyma on T2 weighted MR imaging, consistent with edema or blood-brain barrier breakdown. It is unlikely that stereotactic radiosurgery using the gamma knife will obviate the need for microsurgical removal performed by skilled and experienced microsurgeons. However, radiosurgery is a safe and effective treatment for patients whose medical problems make surgery unacceptably dangerous, those with bilateral tumors or a tumor in their only hearing ear, those who have recurrent tumor despite surgical resection, or patients who refuse microsurgical excision. PMID- 1633447 TI - Gamma knife surgery for sellar and suprasellar tumors. AB - Recent advances in neuroimaging, coupled with stereotactic delivery of ionizing radiation, permit precise, single-treatment irradiation of various intracranial tumors. This article describes the authors' experience with the 201-source 60Co gamma knife. Initial results indicate a potential therapeutic role for radiosurgery in controlling tumor growth and hormone hypersecretion in most patients. The authors believe that radiosurgery should be considered for small pituitary adenomas when prior microsurgery has failed to control tumor growth. Radiosurgery is a primary treatment alternative for patients who are elderly, medically infirm, or refuse microsurgical removal. Further follow-up is necessary to evaluate the long-term tumor control rate, hormonal effects, and tolerance of surrounding critical structures to stereotactic radiosurgery. PMID- 1633448 TI - Radiosurgery of meningiomas. AB - In early experience, radiosurgery proved to be a relatively safe and effective therapy for selected patients with symptomatic meningiomas, including those for whom surgical resection failed. Radiosurgery also has been an effective primary treatment alternative for patients whose advanced age, medical condition, or high risk tumor location preclude microsurgery. The long-term response to treatment, as defined by imaging and clinical findings, is not yet available. In addition, further clinical and laboratory work is necessary to determine the appropriate tumoricidal radiosurgical dose, dose-volume relationships for individual tumors, and the variable radiation tolerance of the different brain structures that closely surround meningiomas. PMID- 1633449 TI - The role of radiosurgery in the treatment of malignant brain tumors. AB - Most studies describing the results of radiosurgery have concentrated on the definitive treatment of small, histologically benign lesions such as vascular malformations, acoustic neurinomas, and pituitary adenomas. More recently, the role of radiosurgery using the gamma knife or LINAC-based systems to treat malignant neoplasms has become better defined. Most solitary metastases, ependymomas, well-circumscribed (on imaging studies) AAs, and a few glioblastomas (and other tumors) have responded dramatically to radiosurgery. Provided that the tumor volume was small (less than or equal to 14 cm3; 30-mm diameter), radiosurgery safely has caused tumor disappearance, shrinkage, or stabilization, regardless of prior surgery, conventional fractionated irradiation, or tumor radioresistance. For patients with recurrent or persistent, small, malignant intracranial tumors, radiosurgical treatment has obviated the need for prolonged hospitalization and has eliminated the risks associated with general anesthesia and open craniotomy. PMID- 1633450 TI - Stereotactic radiosurgery for pineal region tumors. AB - Our present treatment strategy for treating pineal region tumors is shown in Figure 5. We believe that stereotactic biopsy should be the first procedure in pineal region tumors so that a histologic diagnosis can be obtained. Based on the biopsy findings, the appropriate subsequent therapy, whether microsurgery, fractionated irradiation, or stereotactic radiosurgery, can be administered. Although our experience currently is limited to nine patients, we have found that stereotactic radiosurgery is a valuable alternative to microsurgery in the treatment of selected pineal region tumors. PMID- 1633451 TI - Physics and dosimetry of the gamma knife. AB - Since 1968, the gamma knife has been one of the major radiosurgical devices. Although approximately 4300 patients worldwide had been treated with the gamma knife units through June 1990, gamma knife installments in the United States are still rather scarce compared to linear accelerators adapted for radiosurgery. This article describes the basic physical characteristics of the gamma knife, patient set-up procedures, the existing treatment-planning system, the measurements of dosimetry and physical parameters, dose delivery accuracy, and quality assurance procedures. It also includes a vision of future developments and improvements in these areas. PMID- 1633452 TI - Dose prescription and dose-volume effects in radiosurgery. AB - The optimal use of radiosurgery as a treatment technique requires thorough planning, including careful fitting of the high-dose treatment volume to the target volume, and an understanding of the effects of high-dose single-fraction irradiation on both the target volume and the surrounding normal brain. The integrated logistic formula appears to be useful as an aid for predicting the risks of complications from radiosurgery, but greater understanding of the radiation tolerance for all the different areas of the brain (particularly the cranial nerves) is needed. The risk of developing MR imaging-defined changes after radiosurgery for AVMs was significantly related to predictions from the integrated logistic formula. The obliteration rate of AVMs after radiosurgery was volume dependent. Our assessment of the integrated logistic formula to date also indicates that it provides a reasonable guide for predicting complications in the radiosurgical treatment of meningiomas and in the treatment of solitary brain metastases using a combination of fractionated whole-brain irradiation and radiosurgery. The formula did not adequately predict complications in the treatment of AOVMs, however. In the treatment of acoustic tumors, the risks of injury to cranial nerves V, VII, and VIII clearly varied with treatment volume. Further data are needed to fully understand the therapeutic dose-response functions and volume effects for the obliteration of AVMs, the prevention of rebleeding from AOVMs, and growth arrest of meningiomas and acoustic neuromas. PMID- 1633453 TI - Radiobiologic models for radiosurgery. AB - A series of initial radiobiologic investigations have been performed using three animal models. The baboon model proved to be a valuable technique to assess the in vivo radiobiologic response of single-fraction irradiation doses delivered to the primate brain stem. Multimodality neurodiagnostic testing, including CT, MR imaging, xenon-enhanced CT, evoked potential studies, and analysis of CSF myelin basic protein levels, all of which eventually were correlated with neuropathologic examination, enabled detection of lesions produced with high-dose (150 Gy) radiosurgery as early as 6 weeks. Within the first 6 months after radiosurgery, lower doses (20 Gy, 50 Gy) did not result in clinically or neurodiagnostically detectable lesions. The rat arteriovenous fistula model permits analysis of the delayed histopathologic effects of radiosurgery on an experimentally created fistula designed to mimic an AVM. The rat C6 glioma model is designed to evaluate the effect of radiosurgery in an infiltrative tumor that simulates a human malignant brain tumor. These studies are intended eventually to increase our knowledge about the safety and efficacy of radiosurgery in both the normal and tumor-implanted brains. We believe that such fundamental studies ultimately will improve our ability to reach the goals of radiosurgery: to destroy the target and spare the surrounding brain. Eventually, it may become feasible to achieve these goals by combining radiosurgical technique with both radiation sensitizers (for the treated volume) and brain protectors. PMID- 1633454 TI - Stereotactic radiosurgery of brain vascular malformations. AB - Stereotactic radiosurgery using the gamma unit was performed in 251 patients with brain vascular malformations in a 3-year interval. Our efforts include the identification of factors related to both success and complications, including analysis of the malformation location, volume, and dose used. Radiosurgery is a valuable alternative treatment for many patients with brain vascular malformations, including those currently believed to be poor surgical candidates. PMID- 1633455 TI - Physics for radiosurgery with linear accelerators. AB - Radiosurgery had a long development period and, for more than three decades, was used only in a few specialized centers around the world. The development of LINAC based radiosurgical techniques combined with the concurrent advances in imaging modalities during the 1980s, however, caused so much interest in this treatment modality that most major radiotherapy centers now offer this service or at least plan to offer it in the near future. When considering a LINAC for radiosurgical use, one should remember that technical and clinical requirements for accurate radiosurgery are far more stringent than those applied to standard radiotherapy. This is because in radiosurgery, the targeted volumes are much smaller and the dose is usually delivered in a single irradiation session, whereas in radiotherapy, the dose is delivered to a relatively large target volume on a fractionated basis. Linear accelerator-based radiosurgery broadens the scope of radiotherapy departments. The impetus to introduce this service at a medical center usually comes from neurosurgeons, however. Even after the service becomes routine at an institution, it is the neurosurgeon who refers the patient and who plays the most important role in determining the target volume and its location within the brain. The decision on the choice of isodose surface and the prescribed dose, however, belongs to the radiotherapist. It is becoming clear that radiosurgery is a complex treatment modality for which a successful outcome requires a collaborative team effort by several hospital-based professionals, including neurosurgeons, radiation oncologists, neuroradiologists, and medical physicists. As in standard radiotherapy, physics plays an important role in radiosurgery, not only in the development of target localization, treatment planning, and dose delivery techniques, but also in the actual patient contact, from the diagnostic target localization procedures, through treatment planning, to patient preparation on the device and dose delivery. PMID- 1633456 TI - Charged-particle radiosurgery for intracranial vascular malformations. AB - Heavy charged-particle radiation has unique physical characteristics that offer several advantages over photons and protons for stereotactic radiosurgery of intracranial AVMs. These include improved dose distributions with depth in tissue, small angle of lateral scattering, and sharp distal fall-off of dose in the Bragg ionization peak. Under multi-institutionally approved clinical trials, we have used stereotactic helium-ion Bragg peak radiosurgery to treat approximately 400 patients with symptomatic, surgically inaccessible vascular malformations at the UCB-LBL 184-in synchrocyclotron and bevatron. Treatment planning for stereotactic heavy charged-particle radiosurgery for intracranial vascular disorders integrates anatomic and physical information from the stereotactic cerebral angiogram and stereotactic CT and MR imaging scans for each patient, using computerized treatment-planning calculations for optimal isodose contour distribution. The shape of an intracranial AVM is associated strongly with its treatability and potential clinical outcome. In this respect, heavy charged-particle radiosurgery has distinct advantages over other radiosurgical methods; the unique physical properties allow the shaping of individual beams to encompass the contours of large and complexly shaped AVMs, while sparing important adjacent neural structures. We have had a long-term dose-searching clinical protocol in collaboration with SUMC and UCSF and have followed up over 300 patients for more than 2 years. Initially, treatment doses ranged from 45 GyE to 35 GyE. Currently, total doses up to 25 GyE are delivered to treatment volumes ranging from 0.1 cm3 to 70 cm3. This represents a relatively homogeneous dose distribution, with the 90% isodose surface contoured to the periphery of the lesion; there is considerable protection of normal adjacent brain tissues, and most of the brain receives no radiation exposure. Dose selection depends on the volume, shape, and location of the AVM and several other factors, including the volume of normal brain that must be traversed by the plateau portion of the charged-particle beam. The first 230 patients have been evaluated clinically to the end of 1989. Using the clinical grading of Drake, about 90% of the patients had an excellent or good neurologic grade, about 5% had a poor grade, and about 5% had progression of disease and died, or died as a result of unrelated intercurrent illness. Neuroradiologic follow-up to the end of 1989 indicated the following rates of complete angiographic obliteration 3 years after treatment: 90% to 95% for AVM treatment volumes less than 4 cm3, 90% to 95% for volumes 4 to 14 cm3, and 60% to 70% for volumes greater than 14 cm3.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1633457 TI - Infections in neurologic surgery. PMID- 1633458 TI - Infective agents in the central nervous system. AB - Almost all agents can cause infection within the central nervous system. The extent of infection ranges from diffuse involvement of the meninges, brain, or spinal cord to localized involvement presenting as a space-occupying lesion. Epidemiologic considerations, appreciation of the presenting clinical syndrome (acute bacterial meningitis, acute aseptic meningitis, chronic meningitis, or space-occupying lesion), and cerebrospinal fluid analysis facilitate arrival at a diagnosis. PMID- 1633459 TI - Infections in neurologic surgery. Host defenses. AB - Normal host defense mechanisms are effective in preventing central nervous system (CNS) infection. Opsonins and compliment levels are normally low in the CNS, however. The relationship of these factors to CNS infection, specifically surgical wound infection and shunt infection, is discussed. PMID- 1633460 TI - Laboratory diagnostic methods for central nervous system infections. AB - Infections of the CNS have a high mortality, and rapid laboratory diagnosis and adequate antimicrobial therapy are critically important for their management. New techniques assist the clinical microbiology laboratory to isolate and identify micro-organisms more rapidly and accurately than with the use of classic procedures. Microbial identification using immunologic and DNA hybridization techniques has importantly reduced the time needed for the diagnosis of infectious diseases. Culture, however, is still the standard method to confirm the identity of an organism isolated from CSF or CNS sites. With the increase in the number of antimicrobial agents and the recognition of resistance in many isolates, antimicrobial susceptibility testing has become extremely important in the selection of optimal antimicrobial therapy. Communication between the physician and the clinical microbiology laboratory is essential for optimum patient care. PMID- 1633461 TI - Image-guided stereotactic management of non-AIDS-related cerebral infection. AB - Every neurosurgeon can appreciate Dandy's recognition that the drainage of brain abscesses causes trauma to the delicate parenchyma. Over the years, brain surgery has evolved toward management of problems by using less and less invasive techniques and thus gaining ever lower morbidity. Clearly, the advent of better imaging techniques has improved the outcome in patients afflicted with intracerebral infections. The combination of stereotaxy with these imaging techniques is contributing a "zero mortality" in the treatment of these infections. In our series of 29 consecutive patients with non-AIDS-related infections, no patient died as a direct result of a stereotactic surgical procedure. Two patients (7%) had new neurologic deficits after surgery. The only patient left with a permanent disability had a kidney allograft and subacute bacterial endocarditis. His condition deteriorated 6 hours after aspiration of a sterile abscess, when an intra-abscess hematoma was diagnosed and evacuated. In retrospect, this complication may have been avoided by less vigorous aspiration. Three of the four patients with nonviral infections who died were iatrogenically immunosuppressed for their organ transplants. These patients are difficult to treat, and given the current popularity of transplantation procedures, neurosurgeons will face more and more opportunistic infections. In general, the patients with abscesses did well. On the other hand, nonoperative mortality was extremely high for patients with viral encephalitides. This high mortality may have resulted from a delay in diagnosis and treatment or from the unavailability of highly effective antiviral agents at the time the biopsies were performed. The importance of early diagnosis and treatment of infection cannot be overemphasized. T.H. Flewett's warning about the management of HSE applies to the management of all cerebral infections: "It seems clear from everybody's published results [in the papers already given] if we wait to do biopsy until the clinical indications are unmistakable, we have waited so long that the patient, if he survives, will be left a severe neurological cripple." Because it is relatively noninvasive, stereotactic neurosurgery has been used increasingly to diagnose brain masses in patients with AIDS. We recommend its use for establishing diagnoses in all suspected cases of cerebral infection. We agree with Rosenblum et al: Empiric treatment of brain infections should be regarded as "radical." Such treatment should be reserved for patients who have an identifiable source of infection and causative organism or for patients who are clinically too unstable to undergo surgery.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1633462 TI - Imaging of intracranial infection. AB - Modern imaging techniques define the anatomic region infected and the evolution of the disease, help to evaluate treatment efficacy, and frequently can help to determine extra-central nervous system sources of infection, such as sinusitis or mastoiditis. These techniques are discussed by anatomic region, and differential diagnosis based on image pattern is formulated. Special attention is given to the findings in the immunocompromised host and in congenital infection. PMID- 1633463 TI - Use of antimicrobial agents to treat central nervous system infection. AB - When dealing with infections of the central nervous system (CNS), the clinician is often faced with a daunting diagnostic and therapeutic challenge. The clinical presentation can vary from an insidious course that allows time for a full diagnostic examination to fulminant catastrophic events that require immediate therapeutic intervention. Fortunately, a thorough clinical evaluation combined with current laboratory and imaging techniques often allows for a prompt provisional diagnosis of infection. Clinical experience and scientific investigation have laid the basis for rational empiric antimicrobial therapy of CNS infection. The role of antibiotics in the treatment of CNS infections is reviewed and updated, emphasizing current rationale for empiric therapy as well as the proper use of specific antibiotics for specific pathogens. PMID- 1633464 TI - Infections in neurologic surgery. The intraventricular use of antibiotics. AB - Intraventricular antibiotic therapy appears to be a useful treatment modality in those CSF infections in which systemic therapy may fail. Consideration should be given to using this form of treatment when infecting organisms are only sensitive to antibiotics with poor penetration of the CSF (e.g., aminoglycosides and vancomycin) and for cases in which intravenous therapy has failed to sterilize the CSF, toxicity from systemic therapy precludes further increases in dosages, and shunts or other CSF hardware might be expected to reduce the efficacy of systemic therapy by providing a foreign body to harbor organisms. Shunts or reservoirs that are infected may be successfully sterilized with IVT therapy alone or in conjunction with systemic therapy, but this has a lower success rate than cases in which the shunt is removed. There is a wealth of clinical experience with IVT vancomycin and gentamicin that suggests that they are relatively safe. Until more data are available on other aminoglycosides and newer antibiotics, these two agents should be considered the antibiotics of choice for IVT therapy. In situations in which the organism is sensitive to both vancomycin and gentamicin, vancomycin should be used in view of the documented neurotoxicity seen with gentamicin. When gentamicin resistance occurs, amikacin and tobramycin are appropriate alternatives. The high risk of epilepsy with the penicillins and cephalosporins makes them less suited for IVT therapy, although the newer cephalosporins have some promise for IVT therapy. CNS fungal infections can be treated effectively with IVT amphotericin B but with a high risk of significant toxicity. Miconazole appears to be safer than amphotericin B but there is less clinical experience with this drug. Table 1 summarizes the dosages, indications, and toxicity of those antibiotics commonly used for intraventricular administration, which have been reported previously. PMID- 1633465 TI - Antibiotic prophylaxis in neurosurgery. The controlled trials. AB - Systemic antibiotics are effective in reducing the risk of infection after clean neurosurgical procedures. They are less effective in preventing shunt infection, but are strongly recommended in institutions experiencing a shunt infection rate exceeding 15%. The role for antibiotic prophylaxis using topical agents and in the prevention of meningitis associated with cerebrospinal fluid drainage is uncertain. PMID- 1633466 TI - Craniotomy infections. AB - The incidence of craniotomy infections, usually less than 5%, is dependent on many factors, such as how the information is collected and how the percentage is calculated. Because these factors may vary from report to report, incidence figures should be read with skepticism. It is difficult to prove that a given factor contributes to infection. Most routines are based more on personal convictions than on solid evidence. CSF leak is one factor known to have great impact; it should be avoided with painstaking technique and, if it occurs, it should be treated promptly. Solid evidence favoring prophylactic antibiotics for persistent CSF leak is not available; but, until a well-designed randomized study tells otherwise, the high risk of meningitis justifies prophylaxis. Penicillin is adequate for leaks through the nose or the ear. For leaks through the skin, the antibiotic should be effective against staphylococci. The infection register should provide information about prevailing bacteria. In many hospitals, the prophylaxis should cover gram-negative bacilli. CRP is a useful diagnostic aid for detecting postoperative infections. The operation, however, also causes a CRP rise. Daily CRP monitoring, at least for patients with elevated temperature, is recommended. The third-generation cephalosporins are a welcome contribution to the treatment of bacterial meningitis. To avoid side effects, and to keep them potent when they are really needed, they should be used with caution. Most postoperative cases of meningitis are in fact aseptic. If the patient is moderately ill, chloramphenicol is still eligible as the first choice antibiotic. When the bacterial culture is negative, the antibiotic should be stopped. The standard treatment for bone flap infection is removal of the bone flap. The bone flap is essentially devascularized and comparable to a foreign body. The justification of vancomycin prophylaxis has been shown in a randomized study. PMID- 1633467 TI - Cerebrospinal fluid shunt infection. AB - There are distinct clinical situations in which the various methods of treatment are generally used: 1. Medical therapy may be used in the circumstance of an infected, but functioning shunt. However, once a shunt is shown to be malfunctioning, it must be treated surgically to correct both the malfunction and the infection. 2. The one combination therapy that continues to treat the hydrocephalus while obeying surgical principles to remove an infected prosthesis is that of immediate shunt replacement. However, this mode of therapy has worked infrequently. 3. The form of combined surgical and medical therapy that allows time to sterilize the CSF in the absence of a foreign body in situ is that of delayed replacement following removal of the infected shunt. However, this method temporarily discontinues the treatment of hydrocephalus. 4. External ventricular drainage removes the foreign body and continues to treat the hydrocephalus; however, this therapy places the patient at increased risk for more virulent infection. With these points in mind, an algorithm for the treatment of shunt infection can be developed as depicted in Figure 8. Using this common sense approach, most circumstances commonly encountered in the practice of pediatric neurosurgery are dealt with, and the best hope of cure is obtained. PMID- 1633468 TI - Diagnosis and management of brain abscess. AB - Over the past 20 years, the diagnosis and management of brain abscess has been facilitated by a number of technologic advances that have resulted in a significant reduction in mortality. Despite these advances in technology, however, brain abscess remains a serious disease. In this article the nature, pathogenesis, and diagnosis of brain abscesses are discussed. Issues regarding surgical versus nonsurgical management, optimal surgical therapy, choice and duration of antibiotics, and the use of corticosteroids are examined in terms of their impact on mortality and long-term neurologic sequelae. PMID- 1633469 TI - Neurosurgical infections in the compromised host. AB - Granulocytopenia, cellular and humoral mediated immune dysfunction are predisposing factors to the development of CNS infections in immunosuppressed patients. Brain abscess formation in the compromised host is most commonly caused by enteric bacilli, the bacterium N. asteroides, the fungus Aspergillus fumigatus, or the parasite T. gondii. Mucor and the JC virus cause invasive encephalitis in this patient population. CT and MR imaging have greatly aided in the diagnosis of intracranial lesions because of these agents. Stereotactic biopsy-aspiration for diagnosis and to relieve mass effect combined with systemic antimicrobial therapy is the treatment of choice for intracerebral abscess in the compromised host. Organ rejection and chronic immunosuppressive therapy can complicate surgical intervention in these patients. Only with a high index of suspicion, an aggressive approach to diagnosis, and rapid vigorous therapy may we hope to alter the clinical course in this difficult group of patients. PMID- 1633470 TI - Neurosurgical aspects of human immunodeficiency virus infection. AB - The spectrum of neurologic disease that complicates human immunodeficiency virus (HIV) is extremely broad. This article deals with those HIV-related diseases that may occur with a frequency of more than 1% and are of potential neurosurgical importance: those that result from a direct involvement of the nervous system by HIV and those that result either directly or indirectly from the concomitant immunosuppression. Infectious complications are the most common but not the sole cause of neurologic disability in the latter category. Other causes of neurologic disease seen in association with HIV infection include neoplasms, metabolic nutritional disorders, and vascular complications. PMID- 1633471 TI - Cysticercosis cerebri. AB - With increasing immigration from endemic regions, the incidence of cysticercosis in North America is rising. This fascinating disease with its varied presentations may pose complex management dilemmas whose resolutions often require a combined approach to treatment involving medical and, in some cases, selected surgical intervention. The treatment course must be individualized depending on the symptomatology, anatomic location of the cysts, and host inflammatory response. PMID- 1633472 TI - Chronic or recurrent meningitis. Neurosurgical perspectives. AB - Chronic meningitis is not a commonly encountered clinical problem in the day-to day patient care responsibilities of neurosurgeons. It is, however, important for the neurosurgeon to be familiar with the clinical problems, diagnostic challenges, and therapeutic options required to establish a definitive diagnosis. This article concentrates on specific entities causing chronic or recurrent meningitis that may require neurosurgical participation. PMID- 1633473 TI - Pathology of hypertensive arteriopathy. AB - The material covered in this article is divided into two parts: the initial portion summarizes information pertaining to the definition of structural abnormalities, attributed to arterial hypertension, that affects the intraparenchymal cerebral blood vessels. After a brief mention of the brain parenchymal lesions that accompany hypertensive arteriopathies, important modern mechanistic concepts that are derived primarily from animal observations are summarized. PMID- 1633474 TI - Spontaneous intracerebral hemorrhage. PMID- 1633475 TI - Cerebral vascular physiology in hypertensive disease. AB - Experimental advances during the last decade have greatly expanded our knowledge of mechanisms that control cerebral blood flow. In addition to local metabolites, many other factors are important in control of cerebral blood vessels. During chronic hypertension, several mechanisms of cerebral vascular control are altered, with both beneficial and detrimental consequences. The changes should be considered carefully during treatment of chronic hypertension. PMID- 1633476 TI - Hypertensive intracerebral hemorrhage. Epidemiology and clinical pathology. AB - Hypertension is the major risk factor for intracerebral hemorrhage (ICH) and is present in about 50% of patients with ICH. Common clinical findings are focal neurologic deficits at onset, gradually progressive deterioration, and the presence of headache, vomiting, and depressed level of consciousness. The clinical syndromes of ICH at common locations are reviewed. CT scanning has dramatically changed our thinking about ICH and allowed better correlation of neurologic findings with lesions at various sites. PMID- 1633477 TI - Management controversy. Medical versus surgical therapy for spontaneous intracerebral hemorrhage. AB - The controversy surrounding the management of intracranial hemorrhage seems to have been quieted by a large group of recent studies. Future efforts must focus on expansion of the current population screening projects for early detection of hypertension. Whereas some potential exists for new innovative surgical techniques to offer some benefit, it should be kept in mind that most of these patients suffer from end-stage cardiovascular, cerebrovascular, and peripheral vascular disease. PMID- 1633478 TI - Aneurysmal intracerebral hemorrhage. AB - Approximately 20% of all massive nontraumatic intracerebral hemorrhages are caused by ruptured intracranial aneurysms. The possibility for repeated and catastrophic rebleeds, potentially reversible increased intracranial pressure effects, and the need for cerebral vasospasm treatment make the early identification of this cause of hematoma mandatory. PMID- 1633479 TI - Infectious intracranial aneurysms. AB - Infectious cerebral aneurysms are uncommon, accounting for only 2.6% to 6% of all intracranial aneurysms according to autopsy studies. These aneurysms may arise from an intravascular or extravascular source of infection. The vast majority occur in the setting of bacterial endocarditis with an intravascular source of infection due to embolization of fragments of infected cardiac valve emboli. Infectious aneurysms are usually discovered after a devastating intracranial hemorrhage that carries a 60% to 90% mortality. More recently, fungal infectious aneurysms, which carry an even graver prognosis, have become more common. A high index of suspicion and early diagnosis of infectious aneurysms prior to hemorrhage is an important factor in reducing morbidity and mortality. Some lesions are effectively treated with antibiotics alone, but other require surgical intervention. PMID- 1633480 TI - Intracerebral hemorrhage due to cerebral arteriovenous malformations. AB - The most common presentation of a pial arteriovenous malformation (AVM) is spontaneous intracerebral hemorrhage (ICH). The peak incidence of ICH is early in the third decade of life. This article discusses the management of ICH of unknown etiology, ICH from angiographically visible AVM, and ICH from angiographically occult vascular malformations based on the current understanding of the natural history of these disease entities. PMID- 1633481 TI - Intracerebral hemorrhage due to dural arteriovenous malformations and fistulae. AB - Intracerebral hemorrhage is the most devastating complication of dural AVMs. The lesions most at risk are those located at the tentorial incisura and in the anterior cranial fossa. The more common dural AVMs located at the transverse sigmoid sinus and cavernous sinus typically do not hemorrhage and more frequently present with insidious symptoms such as a cranial bruit, tinnitus, or headache. Angiographic appearance of pial draining veins or an intervening varix identifies those patients most at risk for bleeding. An aggressive clinical stance must be taken in this group of patients, with the goal being complete extirpation of the lesion, because any residual AVM can enlarge and recruit pial veins, thus increasing the chances of future hemorrhage. Hemorrhage, which frequently is massive, can be spontaneous or occur after endovascular embolization. When hemorrhage does occur, medical and surgical management must be immediately instituted to avoid secondary brain injury. Therapeutic options include surgery and embolization using particulate material or polymerizing glues, alone or in combination. Although surgery remains the most effective and versatile method for treating dural AVMs, endovascular therapy and stereotactic radiosurgery will likely play more significant roles in treating these lesions in the future. PMID- 1633482 TI - Intracranial hemorrhage associated with primary and secondary tumors. AB - Intracranial hemorrhages are a recognized but relatively uncommon complication of brain tumors. Metastatic tumors are more often associated with hemorrhages than are primary tumors. The types of hemorrhages found include intraparenchymal, subarachnoid, subdural, and epidural. Treatment must be directed at both the hemorrhage and the underlying tumor. PMID- 1633483 TI - Hemorrhagic transformation. The spectrum of ischemia-related brain hemorrhage. AB - Hemorrhagic transformation of ischemic cerebral injury occurs commonly in embolic strokes. The incidence, timing, and clinical consequences of hemorrhagic transformation are reviewed. Hemorrhagic complications resulting from heparin therapy and results from recent preliminary thrombolytic treatment trials are discussed. PMID- 1633484 TI - Hemorrhagic stroke due to cerebral vasculitis and the role of immunosuppressive therapy. AB - Cerebral vasculitis may occur in isolation or in conjunction with a systemic illness. Although a relatively infrequent cause of intracerebral or subarachnoid hemorrhage, it should be considered in a setting of relevant systemic symptoms, an unexplained progressive neurologic disorder, or in a patient lacking risk factors for hemorrhagic stroke. Diagnosis may be difficult because the results of most studies may be normal or nonspecific. Because treatment is effective in many of the cerebral vasculitides, vigorous pursuit of the diagnosis is warranted. PMID- 1633485 TI - Cerebral amyloid angiopathy and moyamoya disease. AB - The incidence, clinical manifestations, diagnosis, and management of cerebral hemorrhage from amyloid angiopathy and moyamoya disease are reviewed. Particular attention is given to pathophysiologic mechanisms producing cerebral hemorrhage in these conditions, the diagnosis based on characteristic CT and angiographic appearances, and the role of surgery in comprehensive management. PMID- 1633486 TI - Hematologic causes of intracerebral hemorrhage and their treatment. AB - Spontaneous ICH is an unusual and potentially disastrous event that may complicate primary and secondary hemostatic abnormalities. Among the primary abnormalities, deficiencies of coagulation factors I, VII, VIII, IX and XIII as well as von Willebrand factor have been clearly associated with ICH. Specific factor replacement or supportive management to normalize the hemostatic defect is indicated in each case. Among secondary alterations in hemostasis, thrombocytopenia, platelet function abnormalities, or factor consumption contribute to the risk of ICH in patients with ITP, TTP, disseminated intravascular coagulation, myeloproliferative or myelodysplastic disorders, and exposure to certain medications. The precise incidence of spontaneous hemorrhage among these disorders is unknown but low. Platelet transfusion and fibrinogen replacement are appropriate in specific cases; however, treatment of the underlying cause is usually required. The association of hemorrhage with antithrombotic agents in several settings is better defined. Cessation of the medication is required in each instance. Fibrinogen replacement may be required after the use of fibrinolytic agents. In all cases, an assessment of the precise hemostatic defect is recommended. PMID- 1633487 TI - Delayed traumatic intracerebral hemorrhage. AB - Delayed traumatic intracerebral hemorrhage refers to the appearance of hemorrhage (usually within 48 hours of head trauma) in areas of the brain that were normal in appearance or nearly so on the CT scan taken shortly after injury. Neurologic deterioration is common but is not universally the rule. The frequency of delayed traumatic intracerebral hemorrhage is variable but is reported to occur in 1% to 8% of patients with severe head injury. The pathogenesis is multifactorial and may result from one or more of the following: coagulation abnormalities, necrosis of blood vessels in areas of brain injury, dysautoregulation, and release of tamponade effect with evacuation of extra-axial hematomas. Outcome is poor, and most series report a mortality of 50% or higher. PMID- 1633488 TI - Iatrogenic intracerebral hemorrhage. AB - Intracerebral hemorrhage as a result of a diagnostic or therapeutic procedure is a rare but potentially devastating event. The fear of hemorrhagic complications influences neurosurgical decision making. The incidence of iatrogenic intracerebral hemorrhage and risk factors for this complication are reviewed for neurosurgical procedures as well as for non-neurosurgical procedures with a known risk of intracerebral hemorrhage. PMID- 1633489 TI - The role of stereotactic technology in the management of intracerebral hemorrhage. AB - Stereotactic techniques have been utilized for more than 40 years in clinical neurosurgical practice. There has been considerable experience with stereotactic techniques in the drainage of intracerebral hemorrhages, although its effectiveness remains controversial. Stereotactic craniotomy, often incorporating advanced computer guidance, is increasingly applied to effect complete resection of small, deep brain lesions. Radiosurgery has become a viable alternative for the treatment of arteriovenous malformations that, in most cases, are untreatable by other means. Currently, stereotaxis is a valuable part of the therapeutic armamentarium available to cerebrovascular neurosurgeons. PMID- 1633490 TI - The future. Prospects of innovative treatment of intracerebral hemorrhage. AB - Aggressive surgical as well as medical management strategies have had limited success with improving outcomes from spontaneous intracerebral hematomas. Future prospects of treatment will undoubtedly focus on less invasive, better tolerated procedures to remove hematomas in select patients. Some success has been achieved with a coupling of stereotactic technology, fibrinolytic agents, and mechanical devices, which can remove solid portions of hematoma through narrow probes. Newer technology also has involved laser endoscopic and small ultrasonic probes to facilitate morcellation and subsequent aspiration without the problems associated with a major intracranial procedure. PMID- 1633491 TI - The tomato 66.3-kD polyphenoloxidase gene: molecular identification and developmental expression. AB - A gene coding for a polypeptide abundant in tomato floral meristems was isolated and shown to represent a tomato 66.3-kD polyphenoloxidase. Analysis of cDNA clones and a corresponding intronless genomic clone indicated that the plastid bound 587-residue-long polypeptide, designated P2, contains two conserved copper binding domains, similar to those found in fungal and mammalian tyrosinases. P2 transcripts and polypeptides are accumulated in the arrested floral primordia of the anantha mutant inflorescences and are equally abundant in primordia of wild type flowers; the gene continues to be expressed at high levels in developing floral organs. In young expanding leaves, P2 protein is concentrated in palisade cells and in epidermal trichomes. Expression patterns of P2 in plant meristems permit molecular distinction between floral and vegetative primordia, and, in a companion study, comparison with dUTPase suggests that the two genes mark two alternative complementary developmental programs in the floral and vegetative meristems of the tomato plants. PMID- 1633492 TI - Localization of protein-protein interactions between subunits of phytochrome. AB - We have used a novel assay based on protein fusions with lambda repressor to identify two small regions within phytochrome's carboxy-terminal domain that are capable of mediating dimerization. Using an in vivo assay, fusions between the DNA binding, amino-terminal domain of lambda repressor and fragments from oat PhyA phytochrome have been assayed for increased repressor activity, an indicator of dimerization. In this assay system, regions of oat phytochrome between amino acids V623-S673 and N1049-Q1129 have been shown to increase repressor activity. These short spans are highly conserved between proteins belonging to the phytochrome PhyA family. Embedded within these sequences are four segments that could potentially form amphipathic alpha helices. Two of the segments are well conserved between PhyA phytochrome and phytochromes encoded by the phyB and phyC genes, suggesting that heterodimers might form by way of subunit interaction at these sites. PMID- 1633493 TI - The Commelina yellow mottle virus promoter is a strong promoter in vascular and reproductive tissues. AB - Commelina yellow mottle virus (CoYMV) is a double-stranded DNA virus that infects the monocot Commelina diffusa. Although CoYMV and cauliflower mosaic virus (CaMV; another double-stranded DNA virus) probably replicate by a similar mechanism, the particle morphology and host range of CoYMV place it in a distinct group. We present evidence that a prompter fragment isolated from CoYMV confers a tissue specific pattern of expression that is different from that conferred by the CaMV 35S promoter. When the CoYMV promoter is used to drive expression of the beta glucuronidase reporter gene in stably transformed tobacco plants, beta glucuronidase activity occurs primarily in the phloem, the phloem-associated cells, and the axial parenchyma of roots, stems, leaves, and flowers. Activity is also detected throughout the anther, with highest activity in the tapetum. In contrast, the CaMV 35S promoter is active in most cell types. The CoYMV promoter is a strong promoter, and when the activity of the CoYMV promoter is compared with that of a duplicated CaMV 35S promoter, it is 30% as active in tobacco suspension cells and up to 25% as active in maize suspension cells. These properties of the CoYMV promoter make it potentially useful for high-level expression of engineered genes in vascular cells. PMID- 1633494 TI - Coordinate regulation of replication and virion sense gene expression in wheat dwarf virus. AB - We have investigated the relationship between viral DNA replication and virion sense gene expression in wheat dwarf virus (WDV), a member of the geminivirus group, by testing a series of deletion mutants in transfected Triticum monococcum (einkorn) protoplasts. Mutants contained a transcription fusion of the chloramphenicol acetyltransferase coding sequence to the virion sense promoter that replaced the viral coat protein coding sequence. The deletion analysis revealed that WDV replication and virion sense transcription can proceed independently and are controlled in part by nonoverlapping elements in the large intergenic region. These data and those from a C2 open reading frame (ORF) frameshift mutant also showed that the product of the C2 ORF (C1-C2 protein) is independently involved in both DNA replication and activation of the virion sense promoter. The amino acid sequences encoded by C2, which are highly conserved in the geminivirus group, show some homology to the DNA binding domain of the myb related class of plant transcription factors. The possible involvement of the host in controlling the function of the C1-C2 protein and the implication of these data for the development of WDV-based gene vectors are discussed. PMID- 1633496 TI - The five key areas of administration. PMID- 1633497 TI - Decision-making and delegating tasks. PMID- 1633495 TI - A maize ribosome-inactivating protein is controlled by the transcriptional activator Opaque-2. AB - Although synthesis of the cytosolic maize albumin b-32 had been shown to be controlled by the Opaque-2 regulatory locus, its function was unknown. We show here that b-32 is a member of the large and widely distributed class of toxic plant proteins with ribosome-inactivating activity. These ribosome-inactivating proteins (RIPs) are RNA N-glycosidases that remove a single base from a conserved 28S rRNA loop required for elongation factor 1 alpha binding. Cell-free in vitro translation extracts were used to show that both maize and wheat ribosomes were resistant to molar excesses of b-32 but not to the dicotyledonous RIP gelonin. We extracted RIP activity from kernels during seed maturation and germination. The amount of RIP activity increased during germination, although the amount of b-32 protein remained fairly constant. Expression of a maize RIP gene under the control of an endosperm-specific transcriptional regulatory may be an important clue prompting investigation of the biological basis for RIP expression in seeds of other plants. PMID- 1633498 TI - Where will you be? Financial planning for the registered nurse. PMID- 1633499 TI - Peruvian nurse visits Saskatchewan. PMID- 1633500 TI - The Children's Wish Foundation: making a wish a reality for a dying child. PMID- 1633501 TI - Traditions and transitions. PMID- 1633502 TI - Victorian Order of Nurses: a part of SRNA history. PMID- 1633503 TI - Caring for practice: the value of nurses. PMID- 1633505 TI - Need for foot care standards. PMID- 1633504 TI - KMK's column. In a prayerbook case, well worn. PMID- 1633506 TI - Advance health care directives: the living will and enduring power of attorney. PMID- 1633507 TI - Applications of intravenous immunoglobulin in haematology. AB - Intravenous immunoglobulin (IVIgG) has many potential applications in haematology both as antibody replacement therapy and as an immune-modulater in autoimmune disorders. Antibody replacement appears to be of value in the prophylaxis of infection in low-grade B-cell malignancies, in bone marrow transplant recipients and in children with AIDS, although optimal treatment strategies have not been assessed and determining which patients are likely to derive greatest benefit has been problematic. IVIgG appears to be effective in the prevention or amelioration of CMV-related pathology if given frequently and has also dramatically improved the survival of patients with established interstitial pneumonia when used in combination with ganciclovir. Intriguingly, IVIgG appears to moderate the severity of GVHD in adult transplant recipients. IVIgG has short term efficacy in most patients with ITP but, as long term remissions are uncommon, it has become necessary to be more selective in the use of IVIgG in this disorder. The response to IVIgG in other immune-mediated cytopenias is similar with generally transient improvement but also with occasional spectacular cures. The treatment of the acquired haemophilias with IVIgG has yielded in vivo and vitro evidence to support the idiotype-antiidiotype theory of IVIgG immune-modulation and has also demonstrated significant differences in the sensitivity of coagulation factor autoantibodies and alloantibodies to IVIgG therapy. IVIgG has several roles in pregnancy related disorders, including the management of both mother and fetus in ITP during pregnancy, the antenatal and postnatal management of platelet alloimmunisation and also in the management of severe rhesus isoimmunisation. IVIgG is safe and well tolerated. The expense of this therapy should be balanced against the likely gains and the overall costs of alternative approaches. PMID- 1633508 TI - Transcription factors, translocations and haematological malignancies. AB - Haematological malignancies arise as a consequence of clonal evolution driven by an accumulation of somatic mutations. Many haematological malignancies are associated with chromosome translocations that have provided powerful tools for the identification of proto-oncogenes implicated in the pathogenesis of leukaemia/lymphoma. The recent characterisation of several translocation breakpoints associated with human haematological tumours has demonstrated that genes encoding transcription factors are frequently involved. Direct alteration of transcription factor activity by somatic mutation may represent a particularly powerful leukaemogenic event. PMID- 1633509 TI - The detection of minimal residual disease in acute lymphoblastic leukaemia. AB - The detection of minimal residual disease in acute lymphoblastic leukaemia (ALL) can be achieved by assessing leukaemia-specific features at a cellular, chromosomal or molecular level. The application of the polymerase chain reaction to the amplification of leukaemia-specific chromosomal translocations and clone specific immunoglobulin and T-cell receptor gene rearrangements allows assessment of the majority of cases of ALL. The sensitivity of detection of this technique is around one leukaemia cell in 10(5) normal marrow cells. A comparative review of the advantages and pitfalls of the different methods of detecting minimal disease is presented. The clinical relevance of such detection is discussed, with early results suggesting that this may have predictive value for future disease relapse. PMID- 1633510 TI - Platelet-neutrophil interactions: their significance. AB - In the vicinity of an acute inflammatory response both cellular and non-cellular elements may interact to modify the overall response. Evidence suggests that leukocytes may play an active role in the modulation of platelet function and vice-versa. This interaction may be abnormal in certain pathological states. Neutrophils have been found to alter platelet behaviour by several mechanisms. These include transcellular metabolism of eicosanoids. Neutrophils utilize platelet-derived arachidonate to increase leukotriene synthesis. Other arachidonate metabolites result from platelet-neutrophil interaction and these differ quantitatively and qualitatively from those arising from either cell-type alone. Another mechanism is the release of a nitric oxide-like factor by neutrophils. Nitric oxide inhibits platelet adhesion and aggregation via guanylate cyclase stimulation. Neutrophils, under different conditions, are potent inducers of platelet calcium flux, aggregation and secretion. This activity is mediated by a neutrophil-derived protease, most likely to be cathepsin G. The interaction of platelets with neutrophils may help to explain some of the pathophysiological events associated with different clinical states. PMID- 1633511 TI - Vitamin K metabolism and nutriture. AB - Vitamin K functions as a co-factor for the post-translational carboxylation of specific glutamate residues to gamma-carboxyglutamate (Gla) residues in several blood coagulation factors (II, VII, IX and X) and coagulation inhibitors (proteins C and S) in the liver; as well as a variety of extrahepatic proteins such as the bone protein osteocalcin. This review outlines some recent advances in our understanding of the metabolism of vitamin K and its role in human nutriture. The introduction of new methodologies to measure the low endogenous tissue concentrations of K vitamins and circulating plasma levels of des-gamma carboxyprothrombin (PIVKA-II) have provided correspondingly more refined indices for the assessment of human vitamin K status. The assays for vitamin K have also been used to study the sources, intestinal absorption, plasma transport, storage and transplacental transfer of K vitamins and the importance of phylloquinone (vitamin K1) versus menaquinones (vitamins K2) to human needs. The ability to biochemically monitor subclinical vitamin K deficiency has reaffirmed the precarious vitamin K status of the newborn and led to an increased appreciation of the risk factors leading to haemorrhagic disease of the newborn and how this may be prevented. Biochemical studies are leading to an increased knowledge of the mode of action of traditional coumarin anticoagulants and how some unrelated compounds (e.g. antibiotics) may also antagonize vitamin K and cause bleeding. There is also an awareness of the possible deleterious effects of vitamin K antagonism or deficiency on non-hepatic Gla-proteins which may play some subtle role in calcium homeostasis. PMID- 1633512 TI - Setting the agenda for health in Europe. PMID- 1633513 TI - Selective serotonin reuptake inhibitors. PMID- 1633514 TI - London's health care again. PMID- 1633515 TI - New research in tuberous sclerosis. PMID- 1633516 TI - Over the counter treatment for candidiasis. PMID- 1633517 TI - Comparison of spontaneous ascites filtration and reinfusion with total paracentesis with intravenous albumin infusion in cirrhotic patients with tense ascites. AB - OBJECTIVE: To compare the effectiveness and safety of spontaneous ascites filtration and reinfusion and total paracentesis plus intravenous albumin infusion in cirrhotic patients with tense ascites. DESIGN: Randomised trial of the two treatments. SETTING: Teaching hospital and district general hospital in Milan. PATIENTS: 45 consecutive cirrhotic patients with recurrent tense ascites and urinary sodium excretion rate less than 20 mmol/day. 35 fulfilled admission criteria and completed the study. 17 received spontaneous ascites filtration and 18 paracentesis plus albumin infusion. MAIN OUTCOME MEASURES: Body weight; urinary volume; serum and urinary electrolyte, serum fibrinogen, and plasma aldosterone concentrations; and plasma renin activity before the procedure and 24 hours and eight days afterwards. RESULTS: Both procedures were effective in all patients. Weight decreased in both groups and showed no substantial increase after eight days. In patients receiving ascites filtration, values decreased significantly (p less than 0.01) after 24 hours for platelet count (mean relative change 0.92; 99% confidence interval 0.86 to 0.98) and serum fibrinogen concentration (0.92; 0.88 to 0.98) but returned to pretreatment values after eight days; no laboratory and clinical signs of disseminated intravascular coagulation were noted. Three patients in this group had fever, which receded spontaneously. One patient in each group had dilutional hyponatraemia. CONCLUSIONS: Spontaneous ascites filtration and reinfusion is an effective treatment for tense ascites. Reinfusion of the patient's concentrated proteins provides savings without compromising safety. PMID- 1633518 TI - Trends in perinatal mortality and cerebral palsy in Western Australia, 1967 to 1985. AB - OBJECTIVE: To analyse the trends in stillbirths, neonatal deaths, and cerebral palsy in all infants born in Western Australia from 1967 to 1985. To relate these trends to changes in perinatal care, particularly in relation to avoidance of intrapartum asphyxia in term infants and the increased survival of low birthweight infants. DESIGN: Descriptive epidemiological study calculating population rates for perinatal deaths and cerebral palsy according to year of birth and birth weight. SETTING: Western Australia. SUBJECTS: All infants born after 20 weeks' gestation or weighing at least 400 g (live and stillborn). MAIN OUTCOME MEASURES: Stillbirths, neonatal deaths (from perinatal death certificates), and cerebral palsy (from a population based register). RESULTS: Overall stillbirth rates fell from 12.1/1000 total births in 1967-70 to 8.1 in 1983-5. Early neonatal mortality fell from 13.0/1000 live births to 4.4 over the same period whereas total cerebral palsy rates remained at around 2-2.5/1000 live births. Death rates fell in all birth weight categories, particularly in low birthweight infants between 1975 and 1985, the period when birthweight data were available. In contrast, cerebral palsy rates in infants under 1500 g rose significantly over this period (from 12.1 in 1968 to 64.9 in 1985). The rise was seen in all spastic categories, including severely and multiply handicapped children. CONCLUSIONS: Large increases in the use of interventions aimed at reducing birth asphyxia and handicaps had not (by 1985) resulted in lower rates of cerebral palsy. This suggests that birth asphyxia is not a major cause. The increased survival of low birthweight infants has resulted in more cerebral palsy in this group, due either to postnatal complications of immaturity or prenatal damage to the fetal brain. These findings have implications for planning perinatal care and for litigation for putative obstetric malpractice in cerebral palsy cases. PMID- 1633520 TI - Regular balloon inflation for patients with chronic bronchitis: a randomised controlled trial. PMID- 1633519 TI - Alcohol consumption as a risk factor for poor outcome after aneurysmal subarachnoid haemorrhage. AB - OBJECTIVE: To evaluate the effect of factors existing before aneurysmal subarachnoid haemorrhage on outcome of haemorrhage. DESIGN: Prospective follow up study. SETTING: Helsinki University Hospital. PATIENTS: 291 consecutive patients (149 men) aged 15 to 65 years admitted within 96 hours after the bleeding. MAIN OUTCOME MEASURES: Potential risk factors (baseline characteristics, health habits, and clinical variables) for poor outcome after haemorrhage (dependent state in the activities of daily living, or death) were studied using multiple logistic regression. RESULTS: One year after haemorrhage, 179 (62%) patients were independent in the activities of daily living and 28 (10%) dependent; 84 (29%) had died. Risk of poor outcome was predicted, after adjustment for sex and age, by clinical condition at admission according to the Glasgow coma scale (p less than 0.0001); occurrence of rebleeding (relative risk 7.1, 95% confidence interval 2.8 to 18.0, p less than 0.0001) or delayed cerebral ischaemia (10.3, 4.2 to 25.4, p less than 0.0001); surgery on an aneurysm (0.13, 0.05 to 0.35, p less than 0.0001); and heavy consumption of alcohol (4.5, 1.8 to 11.0, p = 0.0014). Heavy drinking remained a significant risk factor after additional adjustment for hypertension, body mass index, and presence of intracerebral haematoma. Heavy drinkers had a more unfavourable outcome after rebleeding and delayed ischaemia than did others with rebleeding or ischaemia. Those who had salicylates in urine on admission had delayed ischaemia with fixed neurological deficits less commonly than others. CONCLUSIONS: Heavy drinking impairs outcome mainly through severe rebleeding and delayed ischaemia and to a lesser extent through a poor initial condition and presence of intracerebral haematoma. PMID- 1633521 TI - Pharmacy beyond the dispensary: general practitioners' views. AB - OBJECTIVES: To ascertain general practitioners' attitudes to an extended role for community pharmacists. DESIGN: Postal questionnaire to a 1 in 6 sample of general practitioners in the Northern, West Midlands, and Oxford regions (total sample size 1087). MAIN OUTCOME MEASURES: Attitudes towards specific extended roles, pharmacist prescribing of particular drugs, the role of the pharmacist, and the relationship between the professions. RESULTS: 744 questionnaires were returned in a usable form, an overall response rate of 68.4%. Attitudes varied, from a majority in favour of pharmacists reporting adverse drug reactions to a majority against their supervising repeat prescriptions (81% and 36% in agreement respectively). A similar range of attitudes was shown to pharmacist prescribing, from 84% in agreement with their prescribing nicotine chewing gum (deregulated since the survey) to 11% agreeing to their prescribing cimetidine. About half the respondents thought general practitioners should be allowed to dispense and a third that pharmacists "should stick to dispensing." 27% agreed that pharmacists were too influenced by commercial pressures to give unbiased advice. CONCLUSIONS: Most doctors would favour an extension of the activities of community pharmacists but worry about their role in screening and counselling patients and in prescribing. Despite relationships being generally felt to be good, there may be a need for better communication and cooperation locally and for proper evaluation of initiatives to extend the role of the pharmacist. PMID- 1633522 TI - Practice managers and practice management. PMID- 1633523 TI - Health services research: a case of need or special pleading? The Committee of Heads of Academic Departments of Public Health. PMID- 1633524 TI - ABC of colorectal diseases. Intestinal stomas. PMID- 1633525 TI - Non-Hodgkin's lymphoma. I: Characterisation and treatment. PMID- 1633526 TI - Potentiation of aluminium absorption by effervescent analgesic tablets in a haemodialysis patient. PMID- 1633528 TI - Diets that protect against coronary heart disease. PMID- 1633527 TI - Cholesterol and total mortality: need for larger trials. PMID- 1633529 TI - Doctors and control of major releases of chemicals. PMID- 1633530 TI - Progression of borderline abnormalities on cervical smear testing. PMID- 1633531 TI - Progression of borderline abnormalities on cervical smear testing. PMID- 1633532 TI - Progression of borderline abnormalities on cervical smear testing. PMID- 1633533 TI - Tuberculosis contact tracing. PMID- 1633534 TI - Tuberculosis contact tracing. PMID- 1633535 TI - Hazards of transmission of HIV during invasive procedures. PMID- 1633536 TI - Life insurance and HIV tests. PMID- 1633537 TI - Minimising psychosocial disabilities of multiple sclerosis. PMID- 1633538 TI - Medical abortion. PMID- 1633539 TI - PPP and physiotherapy for senior citizens. PMID- 1633540 TI - Study of factors in atherogenesis. PMID- 1633541 TI - Patterns of hospital medical staffing. PMID- 1633542 TI - Neonatal intensive care and the NHS reforms. PMID- 1633543 TI - Patterns of hospital medical staffing. PMID- 1633544 TI - Checking quality of health care records. PMID- 1633545 TI - Doctors and managers. PMID- 1633546 TI - Giving more information about drug treatment. PMID- 1633547 TI - Public attitudes to smoking in Avon. PMID- 1633548 TI - Ethics and multicentre research projects. PMID- 1633549 TI - Ethics and multicentre research projects. PMID- 1633550 TI - Ethics and multicentre research projects. PMID- 1633551 TI - Central-peripheral and rostral-caudal organization of the innervation of the saccule in a cichlid fish. AB - Saccular eighth nerve arbors were examined in the cichlid fish Astronotus ocellatus to determine if their morphology varies with saccular location. The saccule was divided into four regions: rostral-central, rostral-peripheral, caudal-central, caudal-peripheral. Arbors were filled with cobaltous-lysine. Axon diameter, maximum arbor width, and number of terminal points were taken as quantitative measures. Differences in these measures among the four different saccular regions were evaluated using an analysis of variance. The results indicate two types of organization: central-peripheral and rostral-caudal. The central-peripheral differences involve all three quantitative measures. The central saccule is innervated by arbors with larger axon diameters, larger arbor widths, and more terminal points than the peripheral saccule. The rostral-caudal organization involves only two measures. The rostral saccule is innervated by arbors having larger axon diameters and smaller arbor widths than the caudal saccule. In the oscar, we know of no other parameters that are organized along the rostral-caudal dimension. These findings of a spatial organization of innervation suggest to us that the oscar saccule is not homogeneous in function. PMID- 1633552 TI - Retinal projections in the cane toad, Bufo marinus. AB - The location and extent of retinorecipient areas in the cane toad, Bufo marinus, were established by anterograde transport of cobaltic-lysine complex from the cut optic nerve. Most of the labeled optic axons travelled in the marginal optic tract, while others were in the axial optic tract, and/or the basal optic tract. Retinal projections terminated in both contralateral and ipsilateral targets. In addition to the optic tectum, the main visual center, retinorecipient areas included the suprachiasmatic nucleus, rostral visual nucleus, neuropil of Bellonci, corpus geniculatum thalamicum, ventrolateral thalamic nucleus (dorsal part), posterior thalamic neuropil, uncinate neuropil, pretectal nucleus lentiformis mesencephali and basal optic nucleus. While all of these retinorecipient areas receive optic fibers from both eyes, the ipsilateral retinal projections were observed to be generally sparser than those from the contralateral retina. A sparse optic fiber projection covers the surface of the ipsilateral optic tectum and is most prominent rostromedially and caudolaterally. The position and the extent of each of the retinorecipient areas were determined in relation to a three-dimensional coordinate system. Morphometric analysis showed that 85.3% of the retinorecipient area is in the contralateral optic tectum, 10.4% in contralateral non-tectal areas, 1.6% in the ipsilateral optic tectum and 2.7% in ipsilateral non-tectal areas. The presence of an ipsilateral tectal projection and the well defined pretectal visual neuropil complex may be related to the highly developed visual behavior and visual acuity of Bufo marinus. PMID- 1633553 TI - Axial motor organization in postmetamorphic tiger salamanders (Ambystoma tigrinum): a segregation of epaxial and hypaxial motor pools is not necessarily associated with terrestrial locomotion. AB - The axial motor column has undergone a major reorganization during the evolution of vertebrates. In aquatic anamniotes including lampreys, goldfish, and mudpuppies, epaxial and hypaxial motoneurons are intermingled in the column. In contrast, epaxial and hypaxial motoneurons are spatially segregated in water snakes, rats, and monkeys, apparently as a consequence of an isomorphic mapping of motoneuron location onto the position of innervated muscle in the embryonic myotome. The presence of these two very different arrangements of motoneurons requires a major restructuring of the motor column during vertebrate evolution. The time of this reorganization is unknown. All amniotes studied to date have an epaxial/hypaxial segregation, and all anamniotes do not, suggesting that the map arose with the origin of amniotes. All the anamniotes examined previously were permanently aquatic, however, and the map might therefore be associated with terrestrial locomotion. If so, we would expect terrestrial anamniotes to have an arrangement of motoneurons like that in amniotes. We studied the organization of motoneurons innervating the trunk muscles of postmetamorphic, terrestrial tiger salamanders and asked whether their motor columns are more like those of amniotes or those of aquatic anamniotes. The motor column in tiger salamanders is similar to that seen in aquatic anamniotes and very like that in mudpuppies--permanently aquatic salamanders. There are several classes of motoneurons with morphological similarities to the primary and secondary motoneurons characteristic of aquatic anamniotes. Epaxial and hypaxial motoneurons show no obvious morphological differences and occupy extensively overlapping positions in the motor column. The only epaxial/hypaxial distinction is the presence of a few, small, relatively undifferentiated motoneurons located subadjacent to the ependymal layer. These motoneurons are filled only by horseradish peroxidase (HRP) applied to hypaxial nerves. They are probably newly born motoneurons, and their presence suggests continued addition of motoneurons, even in adult salamanders. We conclude that the epaxial/hypaxial segregation seen in amniotes is not necessarily associated with terrestrial locomotion. The segregation and the topographic map it reflects may have arisen in conjunction with the origin of amniotes. If they instead arose prior to the origin of extant amphibians, they must have been secondarily lost in those salamanders studied to date. An examination of the motor column of other amphibians should help to resolve this issue. PMID- 1633554 TI - Call patterns and basilar papilla tuning in cricket frogs. I. Differences among populations and between sexes. AB - Male cricket frogs (Acris crepitans) produce a broad-band, high frequency advertisement call with a single spectral peak (the dominant frequency). We measured the dominant frequencies of male calls from six populations in central Texas and one from Indiana and compared them to the tuning of basilar papilla afferents in males and females. Averaging over all populations, mean call dominant frequency was 3.69 kHz, mean male basilar papilla tuning was 3.63 kHz, and mean female basilar papilla tuning was 3.17 kHz. Among populations, mean dominant frequency varied from 3.56 kHz to 3.82 kHz. Dominant frequencies were slightly higher in the more eastern Texas populations occupying pine forest habitats than in the more western populations occupying open grassland habitats. Changes in dominant frequency in a population coincided with changes in tuning of both male and female basilar papillae. Furthermore, within populations females were tuned on average lower than males and lower than the mean dominant frequency of calls in their own population. We suggest that the coincident changes in calls and basilar papilla tuning plus the sexual difference in tuning indicate that female mate choice would be directed toward males from her home population with low frequency calls or toward males from foreign populations with average calls lower in frequency than those in her home population. This in turn suggests that any gene flow between populations would be biased from east to west and from forest to open habitats. PMID- 1633556 TI - Oculomotor and sensory mesencephalic trigeminal neurons in lungfishes: phylogenetic implications. AB - The location and number of neurons in the brainstem with projections to the eye muscles were investigated by means of fluorescent tracers in the African lungfish Protopterus dolloi. The oculomotor nucleus (M III) projects bilaterally with a ratio of 3:1 (70 ipsilateral, 20 contralateral neurons). Three subdivisions of this nucleus can be differentiated: one projects exclusively ipsilaterally, another projects exclusively contralaterally, and a third component projects bilaterally. The trochlear nucleus (M IV) is located caudally, distinct from M III, and projects predominantly to contralateral eye muscles with a ratio of 6:1 (18:3 neurons). The abducens nucleus (M VI) contains about 30 neurons with ipsilateral projections only. There is no evidence for an accessory abducens nucleus in Protopterus. Intraocular injections of tracers do not reveal any retinopetal projections in Protopterus. The mesencephalic trigeminal nucleus (Mes V) of Protopterus and Neoceratodus contains about 540-590 neurons on each side. In juvenile Protopterus, up to 75 Mes V neurons are located caudally in a ventral projection of the tectum above the velum medullare anterius. Fifty-five Mes V neurons (10% of the total number) have processes that exit the brain with the trochlear nerve. The relatively large number of Mes V neurons in lungfishes correlates with the well developed jaw musculature. The present study provides the first conclusive evidence for the location of oculomotor subdivisions in the brain of a lepidosirenid lungfish. The organization of the oculomotor nucleus is consistent with the observation that lungfishes possess the pattern of eye-muscle innervation seen in elasmobranchs and supports the unconventional view that lungfishes may be the sistergroup of elasmobranchs. PMID- 1633555 TI - Call patterns and basilar papilla tuning in cricket frogs. II. Intrapopulation variation and allometry. AB - We determined the influence of body size on the male advertisement call's dominant frequency and basilar papilla's (BP) tuning in male and female cricket frogs (Acris crepitans) in two Texas populations (Wimberley and Stengel Ranch). In both populations, call and tuning characters correlated negatively with body size; females were larger than males and their BPs were tuned to a lower frequency. Analysis of covariance showed that neither the sex difference in tuning nor the population differences in calls or tuning were due to the difference in body size alone, but instead represented differences in the allometric relationships of each character with body size. The analysis implied that differences between sexes or populations were due more to shifts in the Y intercept rather than the slope of the relationship with body size. This suggests a developmental model in which sexes or populations possess resonant structures in the ear or larynx with similar growth rates but different starting points or initial growth phases, resulting in different frequency characteristics as adults. The examination of the relationship between female BP tuning and male call dominant frequency predicts potentially different patterns of sexual selection in the two populations, with the Wimberley population males subject to much greater directional selection for low frequency calls. PMID- 1633557 TI - [Description of a new disease, pancreatic lithiasis with radiotransparent calculi]. AB - 118 patients presenting with pancreatic lithiasis were consecutively observed in our service. They underwent both an endoscopic pancreatography and good plain films of the abdomen. Calculi were classified in 3 groups: 1) Radiolucent calculi (17 cases, 5 females; 4 hereditary cases) are build up of amorphous residues of lithostathine S. This disease is not related to either alcohol, diet or tobacco. 2) Taget calculi (27 cases, 4 females; 3 hereditary cases) have a radiolucent core as in 1 and a peripheral calcification. They are a late evolutionary stage of radiolucent lithiasis. The frequency of females and of hereditary cases is significantly greater in form 1 + 2 than in form 3. These two forms are a newly described disease without relationship with nutrition, alcohol or tobacco but the peripheral calcification of radiolucent calculi is favoured by alcohol and tobacco. This disease could be hereditary. 3) Calcic lithiasis (74 cases, 8 females, 2 hereditary cases) is the most frequent form of pancreatic lithiasis. Its cause is nutritional. PMID- 1633558 TI - [Eulogy of Pierre Bourgeois (1901-1991)]. PMID- 1633559 TI - [Potentiation of the acute toxic effects of cocaine by ethyl alcohol]. AB - Ethyl alcohol increases significantly the lethality of cocaine intoxication in the rat. This lethality is not modified by nicardipine or flunarizine, antidotes to cocaine, and might be due to the formation of a newly identified active metabolite cocaethylene. In addition alcohol like cocaine inhibits the baro receptor reflex. PMID- 1633560 TI - [Detection of anti-HIV antibodies prenatally, prenuptially and at the time of induction into national service]. PMID- 1633561 TI - [Juvenile amyotrophic lateral sclerosis. Study of 43 cases]. AB - The authors reported 17 cases of common form of juvenile amyotrophic lateral sclerosis (ALS), 14 cases with spastic paraplegia and peroneal atrophy, and 12 other cases belonging to one single family with spastic pseudo-bulbar paraplegia. The absence of sensory disturbances, the normal motor and sensory conduction velocities, the normal feature of sensory nerve biopsy allowed to include these 3 groups of patients in the frame of Juvenile ALS which is chronic and benign disease. The authors discussed these observations on the light of the literature data on familial spastic paraplegia and primary lateral sclerosis. PMID- 1633562 TI - [Recent data on the epidemiology of dengue fever]. AB - Because of its haemorrhagic forms often with shock syndrome, dengue fever is presently one of the most important pediatric health problems, particularly in South-east Asia. The natural reservoir of dengue is now constituted by urban human populations; travellers are the only dissemination factor of the viruses from one country to another, and all vectors are domestic species of the genus Aedes; in these mosquitoes, a vertical transmission can take place. The persistence mechanisms of dengue fever are closely related to demographic explosion, uncontrolled growth of towns and deterioration of urban environment which comes of it. The spreading mechanisms of outbreaks are related to dramatic increase of travels and the variable susceptibility of the natural Aedes populations to the viruses. All these factors appear to be directly connected with human activities; they were submitted to considerable changes since World War II and the epidemiology of the disease has been widely modified; the incidence of the disease is continuously growing year after year, building up a very worrying situation, more especially as we have no etiologic treatment nor vaccine against it. PMID- 1633563 TI - [Occupational dust exposure and chronic obstructive bronchopulmonary disease. Etiopathogenic approach to the problem of compensation in the mining environment]. AB - In order to support the hypothesis of a causal relationship between exposure to respirable coal mine dusts and chronic obstructive pulmonary disease (COPD), investigations were performed to assess the biological disorders affecting the distal air spaces in coal workers with pneumoconiosis. Broncho alveolar lavage studies demonstrated a continual influx of mononuclear phagocytes loaded with mineral particles, associated with neutrophils in small number, in smokers as well as in non smokers. The alveolar macrophages were in activated state, spontaneously releasing various mediators, particularly interleukin I, Tumor necrosis factor alpha and superoxide anion. So, they appeared as responsible both for a chronic inflammation of the distal airways and for a protease-antiprotease imbalance leading to pulmonary emphysema, partly due to an oxidative inactivation of alpha 1 antiprotease inhibitor. In spite of additive effect of tobacco smoke, as shown by longitudinal studies of lung function in coal miners, it is now reasonable to consider the evidence of association between coal mine exposure and COPD to be sufficiently strong to infer causality, and to justify compensation for COPD in coal miners with or without radiological evidence of pneumoconiosis. PMID- 1633565 TI - An algorithm to fit the Gompertz function to growth curves. AB - An algorithm to fit the Gompertz growth function is presented. This algorithm is easy to program on a microcomputer. The algorithm is based on employing a searching technique to solve a set of equations derived from the Gompertz function. Its application may prove valuable when access to a computer mainframe is difficult. Such a method may be useful in construction of a specific growth curve in biology, or as a managerial tool in livestock enterprise, as well as in the clinical treatment of tumors. Demonstration of the successful application of this algorithm in experimental livestock growth data are presented. PMID- 1633564 TI - Redesigning, implementing and integrating Escherichia coli genome software tools with an object-oriented database system. AB - This paper reports our exploratory work to redesign, implement and integrate a collection of genome software tools with an object-oriented database system. Our software tools deal with genome data from Escherichia coli K-12, a bacterium that has been studied intensively and provides richer data sets than any other living organism. The object-oriented DBMS used for the integration is ONTOS, a commercial object-oriented system from Ontologic Inc. This redesign and implementation task was performed in two steps. First, C programs were converted into C++, and then the C++ version programs were modified and integrated with an object-oriented modeling of the data to form an ONTOS database application. The first step helps us develop a conceptual view for a DBMS-independent object oriented construct. The second step elucidates what additional DBMS-dependent modification steps are needed to provide persistency to the objects. Examples are included to illustrate steps of the redesign and implementation. Overall, the outcome of this project demonstrates that programs and data can be successfully integrated with an object-oriented database, while providing the objects with persistency and shareability. This paper includes discussions using concrete examples on what advantage the object-oriented database approach provides over the relational database approach. PMID- 1633566 TI - PATMAT: a searching and extraction program for sequence, pattern and block queries and databases. AB - A program has been developed that provides molecular biologists with multiple tools for searching databases, yet uses a very simple interface. PATMAT can use protein or (translated) DNA sequences, patterns or blocks of aligned proteins as queries of databases consisting of amino acid or nucleotide sequences, patterns or blocks. The ability to search databases of blocks by 'on-the-fly' conversion to scoring matrices provides a new tool for detection and evaluation of distant relationships. PATMAT uses a pull-down, menu-driven interface to carry out its multiple searching, extraction and viewing functions. Each query or database type is recognized, reported, and the appropriate search carried out, with matches and alignments reported in windows as they occur. Any of the high scoring matches can be exported to a file, viewed and recalled as a query using only a few keystrokes or mouse selections. Searches of multiple database files are carried out by user selection within a window. PATMAT runs under DOS; the searching engine also runs under UNIX. PMID- 1633567 TI - A method for delineating structurally homogeneous regions in protein sequences. AB - A homogeneous region in a protein sequence is a set of contiguous residues that share common features, concerning physico-chemical, structural and mutational information. This paper presents a method for identifying such homogeneous regions. From a profile describing a given type of biological information along the sequence, the algorithm allows the segmentation of the sequence by optimizing a criterion characterized by two user-defined control parameters: the 'homogenizing degree' of the regions and the 'site neighbourhood' size. We apply the method to the envelope proteins of the human immunodeficiency virus HIV-1, for the identification of homogeneous regions in a hydrophobicity profile and the delineation of variable and conserved regions in a variability profile. PMID- 1633568 TI - A new approach for displaying identities and differences among aligned amino acid sequences. AB - An algorithm is presented for computing degrees of sequence conservation found among aligned amino acid sequences. Sequence identities are calculated for each position of an alignment and average identity values of neighboring positions are figured. The average identity value of the whole alignment is chosen as a limit to discriminate between well and less conserved sequence sections. A second algorithm is given to calculate the degree of divergence of individual sequences compared to the other sequences of the alignment. The approach is easy to use on microcomputers and gives an exact picture of sequence identities and differences in order to determine, first, protein regions of high functional or structural importance among homologous proteins, and, second, significant differences of single sequences that may contribute to individual properties of the analysed protein. The method is illustrated by an example analysing a sequence alignment of higher plant nitrate reductases. PMID- 1633569 TI - Construction of simple pathways and simple cycles in ecosystems. AB - We present software tools for overcoming the problem of combinatorics in the enumeration of simple pathways and simple cycles in a first flow-through analysis of carbon transfer in large ecosystems. Rather than search through the very large number of potential routes in a reasonably sized ecosystem for the relatively small number of actual routes, our main algorithm performs an efficient rule based construction of the actual routes. The enumeration of the unique pathways becomes tractable in terms of CPU time, which increases linearly with ecosystem size and connectedness. Networks of up to 80 entities can be evaluated using our software. PMID- 1633570 TI - The rapid generation of mutation data matrices from protein sequences. AB - An efficient means for generating mutation data matrices from large numbers of protein sequences is presented here. By means of an approximate peptide-based sequence comparison algorithm, the set sequences are clustered at the 85% identity level. The closest relating pairs of sequences are aligned, and observed amino acid exchanges tallied in a matrix. The raw mutation frequency matrix is processed in a similar way to that described by Dayhoff et al. (1978), and so the resulting matrices may be easily used in current sequence analysis applications, in place of the standard mutation data matrices, which have not been updated for 13 years. The method is fast enough to process the entire SWISS-PROT databank in 20 h on a Sun SPARCstation 1, and is fast enough to generate a matrix from a specific family or class of proteins in minutes. Differences observed between our 250 PAM mutation data matrix and the matrix calculated by Dayhoff et al. are briefly discussed. PMID- 1633571 TI - STATUS, SEQSTAT, CSTATUS and LOAD: computer programs that facilitate large DNA sequencing projects. PMID- 1633572 TI - A simple method of avoiding the computational problems of the delta method for the end-user of statistical packages. PMID- 1633573 TI - SERPENT--an information storage and analysis resource for protein sequences. PMID- 1633574 TI - The phantom of the operatory. PMID- 1633575 TI - The KAL-technique. PMID- 1633576 TI - Making every minute count: effective time management. AB - Managing ourselves and putting first things first. That's the essence of fourth wave time management. It's about prioritizing, organizing with set priorities in mind and finding the discipline to achieve these goals. If you and your team can master this, the important, not the urgent, will dictate how you use your time. PMID- 1633577 TI - Patient profiles: worth a thousand words. PMID- 1633578 TI - Psychosocial predictors and sequelae of facial change. PMID- 1633579 TI - Function: the basis of facial esthetics. AB - Inadequate primary surgery, or a failure to establish muscular balance of the anterior face, causes muscular dysfunction. Muscular dysfunction has a nefarious effect on subsequent facial growth. Establishment of muscular balance, as early as possible, provides the best foundation for good esthetics. PMID- 1633580 TI - Assessment of the effectiveness of dental sterilizers using biological monitors. AB - This study was undertaken to evaluate the effectiveness of steam, chemical vapor, and dry heat sterilizers, over a three-year period, in dental operatories subscribing to the University of British Columbia's sterilization monitoring service. A total of 4,579 sterilizer loads were tested. The results demonstrated an overall failure rate of 4.4 per cent. Individual failure rates for each type of sterilizer were: chemiclaves, 4.9 per cent; steam autoclaves, 2.3 per cent; and dry heat ovens, 7.9 per cent. In 38 per cent of these cases, the reasons for failure could be attributed to a definite cause. PMID- 1633581 TI - The ideal composite material. PMID- 1633582 TI - Temporomandibular disorders, facial pain and headache following motor vehicle accidents. AB - Temporomandibular disorders are known to be a possible sequela of motor vehicle accidents, particularly when flexion-extension injury occurs. This paper recognizes the relationship between cervical injury and dysfunction, and temporomandibular dysfunction and headache. The literature related to motor vehicle accidents, whiplash injury, and temporomandibular dysfunction is reviewed, and the etiology, prognosis and management of the trauma associated with head and neck pain and dysfunction are presented. PMID- 1633583 TI - Subcutaneous emphysema following dental treatment: a report of two cases and review of the literature. AB - Subcutaneous emphysema is an uncommonly reported complication of routine dentistry. Two cases are presented, one occurring during root canal therapy and the second during routine restorative dentistry. The etiology and consequences of this phenomenon are reviewed, and the prompt recognition and management of this condition are discussed. PMID- 1633584 TI - Longevity of partial, complete and fixed prostheses: a literature review. AB - A review of the dental literature reveals a lack of consensus as to the longevity of conventional prosthodontic therapy. The reasons for this are suggested and best estimates of the longevity of partial, complete and fixed prostheses are presented based on the available literature. A renewed interest in survival studies, hopefully based on sound parameters that outline the reasons for failure, as well as replacement indicators, is required to update our knowledge of survival rates. PMID- 1633585 TI - Ultraviolet exposure. PMID- 1633586 TI - A method of teaching indirect ophthalmoscopy to beginning residents. AB - The authors describe an effective tool for teaching indirect ophthalmoscopy that is easily constructed from a roll of tape. The materials are inexpensive and readily available. The hollow interior of the roll affords a large pupillary opening, and one does not risk scratching the condensing lens on the metal surface of a commercial model eye. PMID- 1633587 TI - Effect of vitrectomy and cytopreparatory techniques on cell survival and preservation. AB - Obtaining vitreous fluid by means of vitrectomy frequently results in a specimen that is difficult to assess cytologically. We devised an experimental model to examine the effect of the vitrector on human leukemic cancer (HL60) cells in suspension and to evaluate the cytopreparatory techniques of membrane filtration and cytocentrifugation. Eighteen 3-mL specimens of cells at concentrations ranging from 1 to 9 x 10(5)/mL were vitrectomized, and eighteen 3-mL control samples matched for cell concentration were obtained atraumatically. No significant difference in cell loss, as determined by means of staining with nigrosin vital dye, was found at any cell concentration between the vitrectomized and control specimens. The specimens were then processed cytologically. On cytologic assessment it was not possible to distinguish the vitrectomized and control specimens. A higher degree of cell preservation was noted at higher cell concentrations regardless of the cytopreparatory technique, but at lower concentrations membrane filtration resulted in a higher proportion of cytologically assessable specimens than did cytocentrifugation (42% vs. 22%). The results suggest that the vitrector causes minimal cellular damage and that to obtain optimal results both cytopreparatory techniques should be used with all vitrectomy specimens. PMID- 1633588 TI - Night myopia: implications for the young driver. AB - A total of 380 randomly selected patients aged 16 to 80 years who did not have eye disease underwent testing for night myopia between August and October 1989 with a laser speckle generator under both photopic and scotopic conditions. For the first 308 subjects the speckles were continuously run, and for the next 72 subjects a timer was used to minimize the accommodative stimulus. An increase in myopia of 0.75 dioptres or more from the photopic to the scotopic state, equivalent to a visual acuity of 20/45 or less, was considered indicative of night myopia. Overall, 17% of the subjects were found to have night myopia. Of the 26 subjects aged 16 to 25 years in the timer group 38% had night myopia of 0.75 D or more, 23% had night myopia of 1.00 D or more, and 4% had night myopia of 2.50 D, which is equivalent to an acuity of 20/265. The results indicate that driving in the dark could create visual difficulties for certain younger patients that a night myopic correction would eliminate. PMID- 1633589 TI - Hemorrhage associated with localization of melanoma margins during radioactive plaque placement. AB - Accurate placement of a radioactive plaque is essential in brachytherapy of choroidal melanoma. Various localization techniques, including transillumination of anteriorly located tumours and scleral indentation to mark the anterior margin of posteriorly located tumours, have been used in initially placing a plaque over the base of the tumour. Of 40 consecutive patients treated for choroidal melanoma between 1986 and 1990, 8 had posteriorly located tumours, all localized by means of scleral indentation; subretinal hemorrhage occurred in 3 of the 8 during marking of the tumour margins. No hemorrhages occurred in the 32 patients with tumours localized by means of transillumination (p less than 0.01). It is not clear whether the method of marking or the location of the tumour itself contributed to the development of the hemorrhage. Hemorrhage around the base of a tumour may mask the tumour margins, making assessment of the response to therapy difficult. Caution should be used when marking posteriorly located tumours. PMID- 1633590 TI - Oral administration of tranexamic acid in the management of traumatic hyphema in children. AB - In a prospective study 163 patients aged 17 years or less admitted to a children's hospital between April 1985 and December 1990 with traumatic hyphema were treated with tranexamic acid, 25 mg/kg given orally every 8 hours to a maximum of 1500 mg every 8 hours for 5 days. Secondary hemorrhage occurred in 5 patients (3%), none of whom had more than one rebleeding episode. In contrast, 24 (8%) of 316 patients aged 17 years or less admitted to the same hospital between January 1977 and March 1985 with traumatic hyphema who were not treated with antifibrinolytics had a secondary hemorrhage, several more than once, giving a rebleeding rate of 33/316 (10%). The results suggest that tranexamic acid reduces the incidence and number of secondary hemorrhages in children, without significant ocular or systemic side effects. PMID- 1633591 TI - Idiopathic conjunctival granulomas. AB - A 12-year-old white boy presented with a 1-year history of intermittent bilateral follicular conjunctivitis with yellowish bulbar and limbal nodules and few symptoms. Histopathological examination of conjunctival biopsy specimens showed non-caseating epithelioid cell granulomas with giant cell formation. The lesions partially responded to therapy with topical corticosteroids but persisted for another 4 years and then gradually cleared over the next 5 years. A systemic investigation failed to disclose a specific cause. At the time of writing, the nodules had completely resolved and no associated systemic disease had developed. PMID- 1633592 TI - Initial identification of antinuclear-antibody-negative systemic lupus erythematosus on ophthalmic examination: a case report, with a discussion of the ocular significance of anticardiolipin (antiphospholipid) antibodies. AB - A 21-year-old man presented with an acute life-threatening illness that was diagnosed and treated as thrombotic thrombocytopenic purpura. The patient survived and during his recovery noted that his central vision was markedly impaired in both eyes. An ophthalmologic examination showed inflammatory and ischemic changes in the retinal vasculature consistent with a diagnosis of systemic lupus erythematosus (SLE). Review of the patient's clinical and laboratory findings did in fact support a diagnosis of SLE that was negative for antinuclear antibody but positive for anticardiolipin antibody. The authors discuss the importance of an ophthalmic examination in patients with SLE-like syndromes and the significance of positivity for anticardiolipin antibody and other antiphospholipid antibodies in patients with thrombosis in the eye or elsewhere. PMID- 1633593 TI - Psammomatoid ossifying fibroma of the orbit. AB - Psammomatoid ossifying fibroma of the orbit is a distinctive solitary fibro osseous lesion of the orbital bones that histologically has characteristic small, round structures resembling psammoma bodies within a benign spindle cell stroma. We describe a 19-year-old woman with this uncommon orbital tumour. PMID- 1633595 TI - Public information programs: three-ring circus or part of medical practice? PMID- 1633594 TI - Corneal melting after pterygium removal followed by topical mitomycin C therapy. AB - Right corneal melting and scleral necrosis developed in a 77-year-old man 5 months after pterygium excision followed by topical administration of mitomycin C drops (0.4 mg/mL) for 4 weeks. We believe that these were delayed complications of the mitomycin C therapy, and we caution against prolonged use of the drug postoperatively. PMID- 1633596 TI - Laser refractive keratectomy and intraocular pressure. PMID- 1633597 TI - Structural determination of alginic acid and the effects of calcium binding as determined by high-field n.m.r. AB - The nature of the solution conformations of the alginic acid components D mannuronan (poly-ManA) and L-guluronan (poly-GulA) from Azotobacter vinelandii were investigated by both one- and two-dimensional n.m.r. methods. Unequivocal proton assignments for both polymers as well as their constituent monomer units were made based on chemical-shift theory, coupling constant analysis, and nuclear Overhauser enhancement measurements. These data were used to investigate the interactions of poly-GulA and poly-ManA with Ca2+ ion in aqueous medium. Based on relative crosspeak integrals measured in two-dimensional phase-sensitive NOESY spectra of free and calcium-bound polymer, a model for calcium binding is proposed. PMID- 1633598 TI - A convenient method for the preparation of a variety of 13C-substituted D fructose phosphates using readily available enzymes of the glycolytic pathway. AB - Methods are presented for the preparation of a variety of D-fructose phosphates, 13C-substituted at any single carbon site or at any two symmetrically disposed carbon sites, from either 13C-substituted pyruvate or L-alanine. It is demonstrated that millimole quantities of product can be obtained in good yield following a "one-pot" incubation of 13C-substituted precursors with commercially available enzymes and cofactors of the glycolytic pathway. Since it has previously been shown that a wide variety of aldehydes serve as acceptable substrates for the final rabbit muscle aldolase-catalyzed condensation step, the method can potentially be applied to prepare a wide variety of 13C-substituted sugars and sugar phosphates. PMID- 1633599 TI - Analysis of glycosaminoglycan-derived oligosaccharides using fast-atom bombardment mass-spectrometry. PMID- 1633600 TI - Synthesis of a glycosidic affinity ligand for purification of cytidine-5' monophosphosialate synthase. PMID- 1633601 TI - Synthesis of p-trifluoroacetamidophenyl 2-acetamido-4-O-(2-acetamido-2-deoxy-beta D-glucopyranosyl)-2-deoxy- beta-D-mannopyranosiduronic acid, an artificial antigen corresponding to a disaccharide repeating unit of the capsular polysaccharide of Haemophilus influenzae type e. PMID- 1633602 TI - Structure of the acidic exopolysaccharide secreted by Rhizobium leguminosarum biovar. phaseoli CFN42. PMID- 1633603 TI - PCILO quantum-mechanical relaxed conformational energy map of methyl 4-thio-alpha maltoside in solution. AB - A theoretical study is presented of the conformational properties of methyl 4 thio-alpha-maltoside. Quantum-chemical PCILO (perturbed configuration interaction with localized orbitals) energy minimization with evaluation of the solvent effect has been used to calculate semi-rigid and relaxed (phi, psi) conformational-energy surfaces in 1,4-dioxane, methanol, dimethyl sulfoxide, and water. The inclusion of molecular flexibility in the conformational analysis of this disaccharide derivative was found to have a significant effect upon the allowed conformational space of the molecule. Calculations revealed the existence of 15 stable conformers having different internal geometries. The relative abundance of these conformers is strongly influenced by solvent. The locations of the global minima and "virtual" conformations vary with solvent and the flexibility of methyl 4-thio-alpha-maltoside significantly decreases from 1,4 dioxane to water. It was found that the conformational properties of methyl 4 thio-alpha-maltoside differ from those of the corresponding 4-oxygenated analogue, methyl alpha-maltoside. The calculated solution behaviour is supported by very good agreement between the theoretical values mean value of 3JC-4,H-1' = 2.67 and mean value of 3JC-1',H-4 = 5.24 Hz calculated as ensemble averages over all conformers on the relaxed map and the experimental values of 2.95 and 5.15 Hz in water solution. PMID- 1633604 TI - 1H-N.m.r. spectral assignments for two series of heparin-derived oligosaccharides. AB - Six heparin-derived oligosaccharides, ranging in size from di- to octa-saccharide and forming two closely related series differing in structure by the substitution of an unsulfated D-glucuronate for a 2-sulfated L-iduronate residue, have been characterized by 2-dimensional 1H-n.m.r. spectroscopy. In addition to providing new data on hexa- and octa-saccharides, several important changes to previously published data have been found for the two tetrasaccharides. The D-glucuronic acid H-5 proton is assigned to a resonance in the same region as resonances for the H-3 and H-4 D-glucuronate protons, rather than downfield from these resonances as earlier reported. The presence of D-glucuronic acid in the heparin sequence of the series-1 fragments affects the positions of neighboring D glucosamine resonances, in particular shifting the anomeric proton signal in the preceding D-glucosamine 0.1-0.2 p.p.m. downfield. Resonances from the reducing end D-glucosamines differ from internal D-glucosamine resonances both in relative position and in the degree of chemical shift difference between the H-6 and H-6' protons. This work illustrates the usefulness of two-dimensional techniques in determining heparin structure and emphasizes the need for direct analysis, rather than assignment by comparison to model compounds. PMID- 1633605 TI - Mode of formation of quinoxaline versus 2[1H]-quinoxalinone rings from dehydro-D erythorbic acid. AB - The mode of formation of the quinoxaline versus 2[1H]-quinoxalinone rings by the reaction of o-diamines with dehydro-D-erythorbic acid has been investigated. The study was carried out by using one and two molar equivalents of 1,2-diamino-4,5 dimethylbenzene (3b) to give 6,7-dimethyl-3-(1-oxo-D-erythro-2,3,4 trihydroxybutyl)-2[1H]-quino xalinone (4b) and 2-(2-amino-4,5 dimethylphenylcarbamoyl)-3-(D-erythro-glycerol-1-yl )- 6,7-dimethylquinoxaline (6), respectively. The former product exists predominantly as the two furanosyl anomers. Sequential reaction of 4a with 3b has been studied, and the location of each diamine in the product was deduced by using 1H-n.m.r. spectroscopy. A mechanism for the reaction is proposed. Acetate and acetal derivatives of the compound are prepared. PMID- 1633607 TI - Spacer-modified, photolabile tetrasaccharides as analogues of maltopentaose are versatile probes for porcine pancreatic alpha-amylase. AB - The syntheses are described of methyl 4'-O-[4-S-(3-azi-4-alpha-D glucopyranosyloxybutyl)-6-deoxy-4 -thio-alpha-D-xylo-hex-5-enopyranosyl]-alpha maltoside (28), methyl 4-O-[4-S-(3-azi-4-alpha-maltosyloxybutyl)-6-deoxy-4-thio- alpha-D-xylo-hex-5-enopyranosyl]-alpha-D-glucopyranoside (29), and methyl 4-S-(3 azi-4-alpha-maltotriosyloxybutyl)-6-deoxy-4-thio- alpha-D-xylo-hex-5 enopyranoside (30), which are analogues of maltopentaose in which a central glucosyl unit is replaced by an acyclic, four-membered hydrocarbon spacer carrying a photolabile azi group. Only 30 was slowly cleaved by high concentrations of pancreatic alpha-amylase. The Ki values (mM) were 0.15 (28), 2.1 (29), and 2.5 (30). Deactivation of the enzyme by irradiation in the presence severely of 28-30 was 96.4%, 98.1%, and 40%, respectively. There is an indication for regiospecific photoaffinity labelling of the binding subsites of the enzyme. PMID- 1633606 TI - Spacer-modified saccharides for the regioselective photoaffinity labelling of the binding site of an immunoglobulin. AB - The spacer-modified trisaccharides that mimic (1----6)-linked beta-D galactotetraose (Gal4), namely, O-beta-D-galactopyranosyl-(1----6)-S-beta-D galactopyranosyl-(1----11)-8 -azi- 6,7,8,9,10-pentadeoxy-11-thio-D-galacto undecose (12) and O-beta-D-galactopyranosyl-(1----6)-O-beta-D-galactopyranosyl- (1----13)-8-azi-6,7,8,9,10,11,12-heptadeoxy-D-galacto-tri decose (20) were synthesised by coupling disaccharide derivatives with 8-azi-6,7,8,9,10-pentadeoxy 1,2:3,4-di-O-isopropylidene-11-O -tosyl-alpha-D-galacto-undecopyranose (10) and 8 azi-6,7,8,9,10,11,12-heptadeoxy-1,2:3,4-di-O-isopropyli den e-alpha-D-galacto- tridecopyranose (17), respectively. Compounds 12 and 20 had affinities for the combining sites of the antibodies IgA X24 and IgA J 539 similar to those of O beta-D-galactopyranosyl-(1----6)-O-beta-D- galactopyranosyl-(1----11)-8-azi 6,7,8,9,10-pentadeoxy-D-gal acto-undecose (7) and the native ligand Gal4. Tritium labelled 7 chemically modified the heavy and light chains of IgA J 539, whereas 8 azi-6,7,8,9,10-pentadeoxy-D-(11-3H)galacto-undecose (5a) reacted only with the heavy chain. PMID- 1633608 TI - Current bibliography of cell calcium prepared by the University of Sheffield Biomedical Information Service. PMID- 1633609 TI - The effects of Ca2+ and calmodulin on adenylyl cyclase activity in plasma membranes derived from neural and non-neural cells. AB - The regulation of adenylyl cyclase activity by varying concentrations of Ca2+ was examined in plasma membrane preparations derived from a number of neural and non neural cells. Enzyme activity in neural tissue (i.e. cerebellum) neural-derived pheochromocytoma PC12 cells and certain endocrine cells (i.e. pancreatic RINm5f and parathyroid cells) was stimulated by physiologic concentrations of Ca2+ by a calmodulin (CaM)-dependent mechanism. In contrast, adenylyl cyclase activity in non-neural cells (e.g. platelets and GH3 cells) was not stimulated by Ca2+. In these latter sources, enzyme activity was inhibited by increasing concentrations of Ca2+, independent of CaM. In liver membranes, Ca2+ and/or CaM did not alter adenylyl cyclase activity. These results demonstrate that the effects exerted by physiologic concentrations of Ca2+ on adenylyl cyclase activity range from CaM dependent stimulation of activity to no effect, to CaM-independent inhibition of activity. The actions of Ca2+ on adenylyl cyclase may be major contributors to the various synergistic or antagonistic interactions that are seen between cAMP generating and Ca(2+)-mobilizing systems. PMID- 1633610 TI - The effect of endotoxemia on concanavalin A induced alterations in cytoplasmic free calcium in rat spleen cells as determined with Fluo-3. AB - The effects of acute (3 h) and chronic (30 h) in vivo infusions of Escherichia coli endotoxin on the Ca2+ homeostasis of rat spleen cells was investigated. Conditions were established for obtaining reliable estimates of [Ca2+]i in these cells using the newly-developed Ca2+ indicator Fluo-3. The resting [Ca2+]i of splenocytes and T lymphocyte-enriched preparations were 119 +/- 35 and 102 +/- 31 nM, respectively. Treatment of the cells with concanavalin A (Con A) resulted in a rapid increase in [Ca2+]i. The magnitude of the increase was positively correlated with the concentration of Con A, whereas the time required to reach the maximum [Ca2+]i was inversely related to the amount of Con A. The peak [Ca2+]i was attained more rapidly in splenocytes (i.e. less than or equal to 30 s) than in the T cell-enriched fraction (i.e. 1.5-2.0 min). Both the resting [Ca2+]i and the Con A-induced increase in [Ca2+]i were similar to values previously reported for other lymphocyte cell types using different Ca2+ indicators, thereby supporting the values obtained with Fluo-3. Infusions of saline or endotoxin prior to the isolation of the cells did not result in significant alterations of either resting [Ca2+]i or the cells' response to Con A. Since chronic infusions of endotoxin have previously been shown to cause a reduction in blastogenic responsiveness of splenocytes to Con A, these data suggest that the endotoxin-induced lesion occurs distal to the mobilization of intracellular Ca2+. PMID- 1633612 TI - Presence of Na+/Ca2+ exchange activity and its role in regulation of intracellular calcium concentration in bovine adrenal chromaffin cells. AB - The presence of a Na+/Ca2+ exchanger in bovine adrenal chromaffin cells was demonstrated by measuring the efflux of 45Ca2+ which had been preloaded into cells by a brief depolarization. The efflux of 45Ca2+ was dependent on extracellular Na+ (Na+o); 45Ca2+ efflux was significantly decreased by replacing Na+o with N-methylglucamine (NMG), or Li+. Replacement of Na+o by NMG increased the resting intracellular Ca2+ concentration ([Ca2+]i) of freshly isolated chromaffin cells. This could be reversed by adding Na+, suggesting that Na+/Ca2+ exchanger activity was involved in maintaining [Ca2+]i at its resting level. The initial rate of Na(+)-dependent [Ca2+]i recovery after Ca2+ loading by depolarization was dependent on the level of [Ca2+]i. There was an apparent linear relationship between the activity of the Na+/Ca2+ exchanger and [Ca2+]i both in the presence and absence of Na+o. When cells were treated with other stimuli, including 10 microM DMPP or 40 mM caffeine, the ability of the stimulated cells to decrease [Ca2+]i was significantly reduced upon replacing Na+o with NMG. Our data show that the Na+/Ca2+ exchanger is one of the major pathways for regulating [Ca2+]i in chromaffin cells in both resting and stimulated states. PMID- 1633611 TI - Subcellular distribution of cytosolic Ca2+ in isolated rat hepatocyte couplets: evaluation using confocal microscopy. AB - Ca2+ agonists induce Ca2+ waves and other non-uniform Ca2+ patterns in the cytosol of epithelial cells. To define subcellular Ca2+ transients in the cytosol of hepatocytes we examined Fluo-3-loaded isolated rat hepatocyte couplets using confocal microscopy. Optical sections of less than 1 micron in thickness were observed in couplets, and fluorescence from cytosolic Ca2+ signals was readily distinguished from nuclear, mitochondrial, and lysosomal fluorescence. The nature of the noncytosolic components of the fluorescent images was verified by double labelling with the mitochondrial dye DiOC6(3) and with the lysosomal marker acridine orange. Using the line scanning mode of confocal microscopy, measurements of cytosolic Ca2+ were made with a frequency of up to 250 Hz and without significant bleaching. It was found that phenylephrine-induced Ca2+ signals generally began at the basal pole of the hepatocytes, then spread to the canaliculus at average speeds of 80 micron/s. These findings demonstrate the utility of confocal line scanning microscopy for detecting rapid changes in the subcellular distribution of cytosolic Ca2+ in hepatocyte couplets, and suggest that phenylephrine-induced Ca2+ waves radiate in a basal-to-apical direction in this cell type. PMID- 1633614 TI - Does Zimbabwe need geriatric services? PMID- 1633613 TI - Pathways to psychiatric care in Harare, Zimbabwe. AB - A study was carried out on the pathways to psychiatric care in Harare, Zimbabwe. Encounter forms were completed on 48 patients admitted to psychiatric beds. Analysis indicated that there was a by-pass of primary care facilities, with a significant number presenting directly to tertiary care facilities, here were lengthy delays before seeking care, but delays while receiving care were moderate. The sample as a whole was composed of major disorders, displaying severe symptoms, and there was a suggestion that some patients become more disturbed along the pathway. As a whole, the sample is very different to samples screened from primary care settings, and the consequences of this are discussed. PMID- 1633615 TI - Malignant lymphomas in Jos, Nigeria: a ten-year study. AB - One hundred-and-sixty-seven cases of malignant lymphomas (ML) diagnosed in the Jos University Teaching Hospital, Jos, Nigeria, over a ten-year period (1979-88) were reviewed. The overall incidence rate is 13.4 per 100,000 with a median age of 29 years and a male:female ratio of 3:1. Non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) represent 67.7 pc and 32.3 pc cases respectively. Low, intermediate and high grade NHLs account for 51.4 pc, 17.7 pc and 30.0 pc of cases respectively; the collective median age at presentation is 31 years and the male:female ratio is 2:1 (Follicular: 13.3 pc; diffuse 86.7 pc). The small lymphocytic lymphoma is the commonest NHL (38.1 pc); the small non-cleaved cell type (African Burkitt's lymphoma type) accounts for 24.7 pc with an incidence rate of 2.2 per 100,000 within the general population and a median age of 10 years. Hodgkin's disease (median age: 28 years) is the commonest form of ML exhibiting only a single peak in the 21-30 years range. The male:female ratio is 8:1 and histological types associated with poor prognosis predominate. The prevalent clinical presentations is with a painless peripheral lymphadenopathy, the cervical group of lymph nodes is often involved representing 55 pc and 67 pc of NHL and HD cases respectively. Burkitt's lymphoma present primarily as an abdomino-pelvic tumour (67.8 pc of cases). Primary extradonal presentation is seen in 90 pc of MLs, all of which are the NHL group with Burkitt's lymphoma accounting for 80 pc of all cases. PMID- 1633617 TI - Peri-umbilical cellulitis in Nigerian neonates. AB - A retrospective analysis was made of 32 neonates with peri-umbilical cellulitis seen at Wesley Guild Hospital, Ilesa, Nigeria from 1979 through 1989. All were full term and delivered after a normal pregnancy. The male:female ratio was 1.3:1. On admission, the mean (Standard Deviation) post-natal age, weight and duration of symptoms were 7.3 (2.7) days, 3.21 (0.5) kg, and 1.9 (1.3) days respectively. Major features were abdominal distension, extensive peri-umbilical induration and inflammation, and foul-smelling discharge. Most mother had antenatal care, but 60 pc were delivered at home or in the mission house. There were no recognisable maternal risk factors. Hot fomentation and unsterile materials applied to the cord were the apparent causative factors. The case fatality rate was very high (71.9 pc). Recommended treatment was antibiotics and surgical debridement. If hospital delivery were accessible to the less privileged poor, this highly lethal condition could be prevented by facilitating instruction in simple sterile cord care. PMID- 1633616 TI - Child survival in a rural area in Zimbabwe: are we winning? AB - Health teams in a rural district in Zimbabwe have been implementing child survival programmes since 1984. A prospective study of the causes of morbidity and mortality in under-five children was done. Community based surveys assessing nutrition status, immunisation coverage and knowledge and use of sugar and salt solution for diarrhoea were carried out. Malnutrition, acute respiratory infections and diarrhoea accounted for 69.7 pc of the 902 under-fives admissions while 33 (67.4 pc) of the hospital deaths were under-fives. The mortality pattern parallelled that of morbidity. Malnutrition was more common in the dry communal areas and on the commercial estates. Full immunisation coverage rates in the 12 23-month-olds increased from 44.3 pc in 1984 to 70 pc in 1989; and up to 69 pc of the mothers correctly prepared and used sugar and salt solution for diarrhoea management. Although there appears to have been little impact on malnutrition, respiratory infections and diarrhoea, the study shows that a lot can be achieved even in a remote rural district given political will, community involvement, and dedicated staff. The maintenance of the current momentum and the introduction of further socio-economic reforms is a big challenge facing the health teams, community members and politicians. PMID- 1633618 TI - Unusual complications of celestin tube. PMID- 1633619 TI - The second tour. PMID- 1633620 TI - Seasonal variation in the food consumption patterns of the people of Mutambara district of Zimbabwe. AB - The pattern of food consumption among the people of Mutambara was studied during periods in December/January, May, and August. A total of 146 food items were consumed. The largest number of meals missed, mainly lunches, was in May. Home grown foods were consumed to a greater extent in May and August than in the December/January period. Wild and semi-wild vegetables and insects were consumed only in December/January when they were available. PMID- 1633621 TI - The discovery of cell wall active antibacterial antibiotics. PMID- 1633622 TI - ACV synthetase. AB - ACV synthetase (ACVS) is the first enzyme and plays a key role in the biosynthesis of all natural penicillins and cephalosporins. The enzyme is extremely unstable and little had been known about it until recently. This article summarizes the progress in research on this enzyme, including the establishment of a cell-free assay system, stabilization, purification, characterization, and gene cloning. A possible reaction sequence for ACVS catalysis is suggested. PMID- 1633623 TI - Overexpression of vinculin suppresses cell motility in BALB/c 3T3 cells. AB - The content of vinculin, a cytoplasmic protein found in focal contacts and cell cell junctions, was increased in BALB/c 3T3 cells by gene transfection. The vinculin expressed from the full length chicken cDNA, incorporated into focal contacts and its pattern was identical to that of the endogenous protein. Cells stably expressing vinculin by 20% over the endogenous level had altered locomotory properties. In these cells, the ability to migrate into a wound formed in a confluent monolayer and the locomotion of individual cells were drastically reduced. The results provide direct evidence that cell locomotion can be regulated by modulating vinculin expression. PMID- 1633624 TI - Actin based motility on retraction fibers in mitotic PtK2 cells. AB - When PtK2 cells round up in mitosis they leave retraction fibers attached between the substrate and the cell body. Retraction fibers and the region where they meet the cell body are rich in actin filaments as judged by phalloidin staining and electron microscopy. Video microscopy was used to study actin dependent motile processes on retraction fibers. Small, phase-dense nodules form spontaneously on the fibers, and move in to the cell body at a rate of 3 microns/minute. As they move in they increase progressively in phase-density. This movement appears to be related to actin dependent centripetal movement which has been previously studied in lamellipodia. Despite its generality, the mechanism of such movement is unknown, and retraction fibers present some special advantages for its study. Cytochalasin treatment causes nodules to stop moving and dissolve. Withdrawal of the drug causes them to reform and start moving. Surprisingly, movement after cytochalasin withdrawal was often outward, indicating a local reversal of cortical polarity. After a few minutes correct polarity is reestablished by a global control mechanism. The implications of these observations for the mechanism and polarity of actin dependent motility is discussed. PMID- 1633625 TI - Dynamics of neuronal intermediate filaments: a developmental perspective. PMID- 1633626 TI - Lung myofibroblasts. PMID- 1633627 TI - Sibling response to childhood cancer: a new approach. AB - It is well recognized that serious illness in children can have important consequences for siblings who may manifest their concerns as behavioural difficulty. The aim of the present study was to explore sibling psychological response to childhood cancer and to observe the effects that sibling knowledge had on their response. Siblings and parents of patients at the Children's Hospital, Birmingham, were interviewed using the Achenbach Child Behavior Checklist and semi-structured 'Illness Knowledge' questionnaires designed by the first author. Siblings were not experiencing significant behaviour problems. The level of sibling knowledge about cancer was related to the level of sibling social competence but not to the prevalence of behaviour problems. One-third of the siblings were talking to no one at all about their feelings, and sibling feedback yielded some important sibling needs. It was concluded that sibling response to childhood cancer may not necessarily be pathological and may also be mediated by the level of sibling social competence as well as sibling knowledge. PMID- 1633628 TI - NACB 15th annual symposium: Advances in clinical laboratory evaluation of cartilage, bone, and systemic rheumatic diseases. Washington, DC, July 26-27, 1991. PMID- 1633629 TI - Biochemistry of articular cartilage in health and disease. AB - Articular cartilage covers the ends of long bones in synovial joints, providing smooth articulation and cushioning of the underlying bone during joint movement. The tissue can be viewed as a viscoelastic, composite material composed of collagen type II (and smaller amounts of other collagens) entrapping compressed (underhydrated) proteoglycan aggregates which generate a high osmotic/swelling pressure. This abundant extracellular matrix (ECM) is synthesized and turned over by relatively few cells, the chondrocytes. These cells produce a compartmentalized ECM, the components of which are heterogeneous and vary with anatomical location. They also undergo changes with age and altered functional requirements. Articular cartilage contains no separating basement membranes, nerves, lymphatics, or blood vessels. Access to nutrients and elimination of waste products occur via diffusion through the extracellular matrix. The turnover of collagen is much slower than that of proteoglycans. Products of the metabolic turnover of the matrix macromolecules are released continuously into the synovial cavity and ultimately reach the blood circulation where they can be measured as "markers" of metabolic changes. PMID- 1633630 TI - National Academy of Clinical Biochemistry Kodak Lectureship Award Recipient. PMID- 1633631 TI - Cartilage matrix metabolism in osteoarthritis: markers in synovial fluid, serum, and urine. AB - Osteoarthritis is a major cause of disability and early retirement. Yet we lack the means to diagnose the disease in its early stages or to monitor the effects of treatment on the target tissue, the joint cartilage. Neither can we identify the disease mechanisms at the tissue or cell level. Current research focuses on the use of markers of cartilage matrix metabolism in body fluids as a means to diagnose and monitor osteoarthritis. Cartilage proteoglycan, collagen and glycoprotein fragments, as well as proteinases and their inhibitors, are being suggested for this purpose. Structural information on matrix molecule fragments released into body fluids may also help to identify the enzymes active in the destruction of the cartilage, a central issue in osteoarthritis. PMID- 1633632 TI - Serum keratan sulfate--a marker of predisposition to polyarticular osteoarthritis. AB - We have used an ELISA to quantify a highly sulfated epitope present on keratan sulfate, a carbohydrate chain found principally in cartilage proteoglycans. The serum level of the epitope provides an indirect measure of the rate of degradation of cartilage proteoglycans during normal turnover and can be used to diagnose specific abnormalities in keratan sulfate metabolism. Serum levels of the epitope are elevated in a high percentage of patients with osteoarthritis and correlate with the number of joints involved. The elevated rate of proteoglycan turnover in these patients appears to be systemic, affecting not only the degenerating articular surfaces but apparently normal articular cartilages as well. We have postulated that this acceleration in the rate of proteoglycan turnover precedes clinical evidence of degenerative changes; and we discuss the rationale for the contention that this elevation may predispose adult humans to polyarticular osteoarthritis. PMID- 1633633 TI - Autoimmune diseases: overview and current concepts of pathogenesis. AB - No single theory or mechanism can adequately explain all features or pathogenesis of autoimmune diseases. The clinically wide spectrum of autoimmune diseases is best considered as the mosaic of autoimmunity and the many factors involved are genetic, hormonal, immunological, and environmental. These multifactorial considerations help to explain not only the diversity of various clinical diseases encountered but also the differences in clinical manifestations from patient to patient within the same disease group. PMID- 1633634 TI - HLA molecules in autoimmune diseases. AB - The association of certain autoimmune diseases with HLA molecules is being refined through the use of sequence-specific oligonucleotide probes and amino acid sequencing, together with continuing elucidation of the functional features of HLA molecules derived from the milestone description by Bjorkman of the HLA molecular structure. The association of insulin-dependent diabetes mellitus and HLA began with weak associations of Class I antigens (B8 and B15) and progressed to Class II antigens (DR3 and DR4), then to subtypes of DR4 (Dw4, 10, and 14), and now to DQ molecules including the absence of aspartic acid at position 57 of the DQ beta chain and the presence of arginine at position 52 of the DQ alpha chain. In rheumatoid arthritis (RA) the HLA antigen association remains with certain Class II molecules of the DR series (DR4 and DR1) that share amino acid sequences with a restricted number of other DR antigens seen in RA, as well as a segment of the gp 110 protein of the Epstein-Barr virus. Although ankylosing spondylitis has a strong association with the Class I antigen B27, that association is not explained by any of the B27 subtypes defined by monoclonal antibodies, by the eight variable amino acids in B27 subtypes, or by the two unique amino acids on B27. The remarkable antibody cross-reactivity among lymphocytes bearing B27, a synthetic peptide sequence (63-84) of B27, and the 188 193 sequence of K. pneumoniae nitrogenase has provided strong support for molecular mimicry being an important mechanism in the association of HLA molecules with disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1633635 TI - Thyrotropin receptor antibodies: advances and importance of detection techniques in thyroid diseases. AB - The study of autoimmune thyroid disorders (AITD) has greatly contributed to our knowledge of autoimmunity. Graves' disease and Hashimoto's thyroiditis represent two ends of the range of autoimmune responses seen in AITD. Autoantibodies reactive to cytoplasmic antigens are associated with cell damage, and thyrotropin (TSH)-receptor antibodies (TRAb) influence the function and growth of the gland and play a major role in pathogenesis. The heterogeneous nature of TRAb is well accepted. Besides their long-known thyroid stimulating activity, TRAb can act as blocking antibodies or growth-promoting antibodies and, thus, cause hypothyroidism (primary myxedema) or endemic and sporadic goiters, respectively. Advanced methodologies for detection of these antibodies with the TSH-receptor assay and thyroid cell bioassay allow various activities to be measured. Current data using these assays confirm the presence of heterogeneity of functional activities of TRAb(s) in vivo. The activity of predominating antibody may relate to clinical presentation. This indicates a need for paired determinations of both TSH-binding inhibitory immunoglobulin (TBII) and thyroid-stimulating immunoglobulin (TSI) for accurate clinical correlations. Cloning the TSH-receptor gene has clarified its structure and function. The future identification of its epitopes will further delineate the clinical role of these antibodies and may allow development of new diagnostic and therapeutic approaches. PMID- 1633636 TI - Serological detection of disease activity in SLE. AB - Laboratory tests are commonly used to aid in monitoring disease activity in patients with systemic lupus erythematosus. Typically, tests for antinative DNA, complement, acute phase reactants, and sometimes circulating immune complexes are used for this purpose. More recently, tests for complement activation products and immunocyte activation have been suggested. We measured antinative DNA, C4, Westergren sedimentation rate, iC3b, Bb, and sIL-2R levels in a group of 100 patients with SLE evaluated clinically for activity by a modified version of the Systemic Lupus Activity Measure (SLAM); iC3b and Bb were studied in 71 of the patients and sIL-2R in 52. We found that sIL-2R and sedimentation rate correlated best with SLAM, anti-DNA was intermediate, and C4, iC3b, and Bb correlated the least. None of the tests predicted severity of disease, but sIL-2R was highest in patients with active renal disease. PMID- 1633637 TI - Laboratory evaluation of patients with Sjogren's syndrome. AB - Sjogren's syndrome (SS) is a chronic autoimmune disorder characterized by lymphocytic infiltration of the lacrymal and salivary glands, leading to severe dryness of eyes (keratoconjunctivitis sicca) and mouth (xerostomia). SS may exist as a primary disorder (1 degree-SS) or in association with other autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus or progressive systemic sclerosis (scleroderma). Diagnosis of 1 degree-SS is confirmed by minor salivary gland biopsy and the presence of circulating autoantibodies. Minor salivary gland biopsies exhibit focal lymphocytic infiltrates that are present in the majority of lobules. Incorrect methods of biopsy and failure to determine the average focus score are common causes for false-positive and false-negative biopsies. SS patients frequently have a positive antinuclear antibody test due to presence of SS-A (Ro) and SS-B (La) autoantibodies. Molecular analysis has revealed multiple "SS-A" proteins (60 kd, 54 kd, 52 kd) that react with sera from SS patients, as well as a 48 kd SS-B protein. Rheumatoid factor (anti-IgG Fc antibody) in 1 degree-SS patients exhibits restriction in its light chain-associated idiotype, in contrast to RA patients where no restriction of idiotype was detected. Other autoantibodies found in a subpopulation of SS patients include anti-ADP ribose polymerase, anti cardiolipin, anti-mitochondrial, anti-mitotic spindle apparatus, anti-parietal cell, and anti-thyroid associated antibodies. Due to the high frequency of dryness syndromes in patients due to other causes (ranging from drug side effects to normal aging processes), the use of strict criteria for diagnosis of SS will lead to improved cost-efficient medical care avoiding needless anxiety in the patient. PMID- 1633638 TI - Autoantibody specificity in drug-induced lupus and neutrophil-mediated metabolism of lupus-inducing drugs. AB - A long-term side effect of therapy with a variety of drugs is a syndrome resembling the idiopathic autoimmune disease, systemic lupus erythematosus. Essentially all patients with drug-induced lupus display autoantibodies to nuclear histone components whose specificity appears to be related to the higher order structure of histones existing in chromatin. IgG antibodies to H1 and the (H2A-H2B)-DNA complex were observed in most patients with lupus induced by procainamide, hydralazine, and quinidine, whereas the H3-H4 tetramer, comprising half the mass of the nucleosome core particle, was largely nonantigenic. IgM antibodies to (H2A-H2B)-containing chromatin subunits were common also. IgM reactivity was observed with the DNA-free H3-H4 tetramer and with H1, especially in hydralazine-induced lupus. These results suggest that IgM antihistone antibodies may result from autoimmunization with a nonnative form of chromatin, whereas IgG antibodies may be selected for reactivity with H1 and a native form of the (H2A-H2B)-DNA subunit of the nucleosome. The chemical basis for induction of autoimmunity by drugs is unclear because lupus-inducing drugs do not have a common structural feature or biological activity nor are they capable of specific reactions with histones, the principal target antigen. However, in the presence of activated neutrophils, procainamide is transformed metabolically to the cytotoxic procainamide-hydroxylamine. Mixing experiments and cell-free studies demonstrated that procainamide was cooxidized with H2O2 by myeloperoxidase released when neutrophils undergo the respiratory burst and degranulation reactions. Preliminary results indicate other lupus-inducing drugs are also biotransformed by this mechanism suggesting that a common denominator linking these drugs may be the capacity to be oxidized to reactive metabolites by the action of activated phagocytic cells. PMID- 1633639 TI - Gaucher patients with oculomotor abnormalities do not have a unique genotype. AB - Sixteen non-Ashkenazic American children with Gaucher disease who demonstrate slowing of the horizontal saccades are described. Attempts to correlate this specific clinical phenotype with a unique genotype were unsuccessful. Focusing on the three most common mutations, at least five different genotypes were present in these patients. Children with this isolated oculomotor abnormality generally had a diffusely slowed background on EEG, but an otherwise normal neurologic examination, and exhibited earlier and more severe systemic manifestations and mortality. This study emphasizes the need for careful sequential neuro ophthalmologic examinations in Gaucher patients and the need for caution in attempting to make clinical predictions regarding the course of Gaucher disease on the basis of current DNA mutational analysis. PMID- 1633640 TI - Birth prevalence studies of the Crouzon syndrome: comparison of direct and indirect methods. AB - An indirect method for estimating the birth prevalence of the Crouzon syndrome is presented. The fraction of Crouzon syndrome patients in large clinical surveys of all cases of craniosynostosis is calculated and the fractional component obtained is multiplied by the known birth prevalence of craniosynostosis in general. Crouzon syndrome makes up approximately 4.8% of all cases of craniosynostosis. Using a weighted average estimate, birth prevalence was calculated to be 16.5/1,000,000. The results of the indirect method compare favorably with those obtained by the direct method. Nevertheless, because the indirect method is based on a number of assumptions that are easily violated, we cannot recommend its general use except under special circumstances. PMID- 1633641 TI - Mental retardation with blepharo-naso-facial abnormalities and hand malformations: a new syndrome? AB - A syndrome involving facial abnormalities (telecanthus, epicanthus, broad flattened nose, large inverted W-shaped mouth and malformed ears), malformed extremities (camptodactyly, clinodactyly, interdigital webbing and joint hyperlaxity) and mental retardation is described in a girl at birth and at 11 years old. A comparison with Pashayan-Pruzansky syndrome, fetal alcohol syndrome, VATER association, Marden-Walker syndrome and Tel-Hashomer syndrome is discussed. We suggest this patient represents a new malformation syndrome or an extreme phenotypic variant of one of the above-mentioned syndromes. PMID- 1633642 TI - Interstitial deletion of chromosome 1 del (1) (q32 q42): case report and review of the literature. AB - We describe the case of a female infant with multiple congenital anomalies who was found to have a de novo distal intestinal del (1) (q32 q42). The clinical features of other reports of similar deletions are briefly reviewed. No characteristic phenotype seems to be as yet definable due to the limited number of cases published. PMID- 1633643 TI - Further evidence consistent with Yqh as an indicator of risk of gonadal blastoma in Y-bearing mosaic Turner syndrome. AB - An 8-year-old girl with some features of Turner syndrome and karyotype 45X/46XY had developed a bilateral gonadoblastoma in her rudimentary ovaries. Her normal Y chromosome showed the characteristic distal fluorescence, as seen in her father's. Another mosaic, this time 45X/46XidicY, and also with some Turner features had rudimentary ovaries, but no gonadoblastoma had developed at age 14. The nature of her idicY, which showed no fluorescent distal Yq and had one of the centromeres inactivated, was confirmed by in situ hybridisation with a Yp specific probe. Using primers from a human Yp-specific sequence, we amplified DNA extracted from paraffin-embedded ovarian tissue from both cases, and from a normal testicle and a normal ovary as controls. The finding of the expected Y derived PCR product in the rudimentary gonads from these mosaic patients indicates the presence of their Y chromosome in both. We discuss the validity of the findings, and the possible role of sequences in or near the fluorescent part of Yq in the origin of gonadoblastoma in Y-bearing mosaic Turner syndrome. PMID- 1633644 TI - Fragile site Xq27.3 in a family without mental retardation. AB - Routine parental blood analysis for a couple undergoing prenatal diagnosis because of maternal age, revealed a 47,XXX karyotype in the mother and expression of the fragile site Xq27.3 in the father. Additional family studies show the fragile site in the father's sister and her two sons. There is no history of intellectual handicap in this family, nor of any physical manifestations of the Fra(X) mental retardation syndrome. PMID- 1633645 TI - Trisomy 18 mosaicism with complete peripheral lymphocyte trisomy and normal intelligence. AB - We report a patient with trisomy 18 in all peripheral lymphocytes, mosaicism in cultured fibroblasts, mild nonspecific dysmorphic features, and normal intelligence. Trisomy 18 mosaicism with complete peripheral lymphocytic trisomy has not been previously described. The karyotype of lymphocytes is not diagnostic in the absence of congruent morphologic features. PMID- 1633646 TI - On the variable expression of the Brachmann-de Lange syndrome. AB - A mother of normal intelligence and her moderately mentally retarded son, both with the typical facial features of the Brachmann-de Lange syndrome, are reported. We discuss the variable expression of the Brachmann-de Lange syndrome by comparing the autosomal dominant cases with the sporadic or presumed autosomal recessive cases. The autosomal dominant cases show milder symptoms in general. In our opinion, a de novo autosomal dominant mutation causes the severe form of the syndrome, recurrence within sibships being explained by germline mosaicism. In all convincingly autosomal dominant cases we found that the mother is the transmitting parent, suggesting genomic imprinting. PMID- 1633647 TI - Treatment for B-cell-type lymphoma in a girl associated with Bloom's syndrome. AB - A 12-year-old girl suffering from Bloom's syndrome developed B-cell-type lymphoma in the epipharynx. She was identified as having Bloom's syndrome at the age of 3. While the tumor was eradicated completely by induction chemotherapy, the bone marrow suppression was severe and persistent. For this reason, we modified subsequent chemotherapy to a milder form. Thus the remaining therapy could be safely completed. This is the first case clearly diagnosed as having epipharyngeal B-cell-type lymphoma in the Bloom's Syndrome Registry. PMID- 1633648 TI - Severe Silver-Russell syndrome and translocation (17;20) (q25;q13) AB - An 8-year-8-month-old girl with Silver-Russell syndrome (SRS) and a paternally inherited balanced t(17;20)(q25;q13) is described. This observation suggests that an SRS gene(s) maps on chromosome 17 or 20 and that the patient phenotype resulted from either unmasking of heterozygosity or genomic imprinting via paternal disomy. PMID- 1633649 TI - A unique de novo interstitial deletion del(17)(q21.3q23) in a phenotypically abnormal infant. AB - We report on an infant with multiple congenital anomalies possessing a de novo, interstitially deleted no. 17 chromosome. The phenotype includes brachycephaly, club feet, delay of growth and development, and hypertelorism with upslanted palpebral fissures. We are unaware of other reported cases involving such interstitial deletion of 17, or of translocations involving the breakpoint regions observed in our case. PMID- 1633650 TI - An HLA study in 74 Danish haemochromatosis patients and in 21 of their families. AB - HLA-A and -B alleles in 74 Danish patients and 21 homozygous relatives with idiopathic haemochromatosis (IH) were compared with those in a sample of 1719 chromosomes from healthy Danish control subjects. The following alleles occurred with higher frequencies in IH compared to controls: A3: 53.6% vs. 15.1% (Pc less than 0.001); B7: 33.1% vs. 15.6% (Pc less than 0.001); B14: 6.9% vs. 3.0% (Pc greater than 0.05); B38: 5% vs. 0.9% (Pc greater than 0.05); B47: 4.0% vs. 0.4% (Pc greater than 0.05). Pedigree analyses disclosed 19 different haplotypes in IH subjects, compared to 286 haplotypes in controls. The following haplotypes occurred with higher frequency in IH compared to controls: A3,B5: 10.3% vs. 0.3% (Pc less than 0.001); A3,B7: 25.6% vs. 6.6% (Pc = 0.001); A3,B14: 3.4% vs. 0.6% (Pc greater than 0.05); A3,B47: 6.9% vs. 0.2% (Pc greater than 0.05). The major IH marker HLA-A3 was found in 56% of the haplotypes. The patterns of HLA-alleles associated with IH in Denmark show similarities to those in Central Europe, Australia, USA and Canada, being A3,B7 dominated and those in Central Sweden, England and Ireland, being A3,B14 dominated. PMID- 1633652 TI - HIV infection in obstetrics and gynaecology. PMID- 1633651 TI - Human immunodeficiency virus and the immunology of infection. PMID- 1633653 TI - The management of HIV disease in pregnancy. PMID- 1633654 TI - Nosocomial infection and infection control procedure. PMID- 1633655 TI - Clinical manifestations, management and therapy of HIV infection in children. AB - Perinatal infection accounts for the majority of cases of HIV infection in children both in developed and developing countries. Transmission may occur in utero, intrapartum or postpartum as a result of breast-feeding. The actual risk of transmission through breast-feeding is unknown. The majority of infants reported to be infected through breast milk have been infected as a result of a recently acquired HIV infection in the mother. Infants with HIV infection frequently present with clinical symptoms early in life. There is a broad spectrum of clinical findings in paediatric HIV infection, with opportunistic infections and multiorgan system involvement being common. The management of infants born to seropositive mothers includes routine paediatric care as well as careful clinical and laboratory monitoring for evidence of HIV infection. Infants who are seronegative with normal clinical and immunological findings at 18 months of age are considered uninfected. The prognosis and outcome of infants with HIV infection have improved considerably with earlier diagnosis and the availability of specific antiviral therapy. Modalities of therapy include frequent medical evaluation, aggressive diagnosis and treatment of infection, prophylaxis for Pneumocystis carinii infection, the use of intravenous gamma-globulin and specific antiviral therapy, such as zidovudine, didanosine or other drugs in development through clinical trials. HIV infection in children is a chronic illness and requires a comprehensive, family-oriented approach to care. With longer survival, children require support systems and an atmosphere of care and understanding to give them a good quality of life as well as prolonged survival. PMID- 1633656 TI - The situation in Africa. AB - More than three million women world-wide are infected with HIV, and women will constitute 40% of the new AIDS cases in 1990-1991. Unlike in the industrialized world, HIV in Africa is heterosexually transmitted and thus affects at least as many women as men. Already the leading cause of death in a major African city, HIV may be spreading to rural areas. In spite of improvement in surveillance, under-reporting makes it difficult to project trends, document differences within and between urban and rural areas, and identify at-risk groups. Increasing evidence shows that STDs play a major role in spreading the HIV epidemic. Male-to female transmission is more efficient owing to factors related to the pathogen and the host. Ulcerative STDs such as chancroid, syphilis and herpes facilitate HIV entry through mucosal discontinuation and recruitment of HIV target cells. The role of non-ulcerative STDs such as gonorrhoeal, chlamydial and trichomonal infections needs further elucidation. Lack of circumcision, traditional healing practices and oral contraceptives may affect the risk of viral transmission, but may not be major or modifiable risk factors. Pregnancy and pregnancy-associated immune alterations do not seem to affect the clinical course of HIV/AIDS in African women or impair immunocompetence. Maternal HIV can adversely affect pregnancy outcome in Africa, causing low birth-weight, prematurity, intrauterine and intrapartum fetal death. The risk for these outcomes is likely to depend on the degree of immunological and clinical deterioration. Breast-feeding does not appreciably increase the risk of HIV transmission to the infant and should be actively promoted in Africa. Control of HIV/AIDS in Africa, in the absence of an effective vaccine, will focus on behavioural changes through health education and condom use. High frequency STD transmitter core groups, mainly prostitutes and their clients, are currently the target of prevention campaigns which are proving to be successful and affordable. PMID- 1633657 TI - Gynaecological problems and infertility. PMID- 1633658 TI - Contraception and safer sex. PMID- 1633659 TI - HIV testing programmes in pregnancy. PMID- 1633660 TI - HIV counselling for women of reproductive age. AB - As the HIV pandemic has evolved over the past decade, the numbers of women affected by this virus have swelled. HIV counselling and testing is increasingly becoming a standard of obstetric and gynaecological practice, and women's health care providers will need to incorporate the appropriate knowledge and skills in order to provide these services. This article discusses preparation for integrating HIV counselling and testing into the women's health-care setting and the provision of HIV pre-test and post-test counselling and follow-up to women of reproductive age. Key preparation issues, including those of documentation, consent, confidentiality and risk assessment, are described. Counselling issues of particular significance for HIV-positive women, including reproduction, sexuality, care-giving, maintenance of health and long-term planning, are addressed. Planning and commitment are critical factors in the implementation of HIV counselling and testing in women's health-care delivery settings. PMID- 1633661 TI - The effect of HIV infection on pregnancy outcome. PMID- 1633662 TI - Vertical transmission. AB - Since AIDS was first described in children, much has been learnt about the epidemiology, clinical presentations and natural history of perinatally acquired HIV disease. As yet, several questions remain unanswered about the pathogenesis of vertical transmission, the relative risk associated with each mode of transmission, the rate of transmission from mother to child, and the factors that might contribute to the efficiency of transmission. Data presented thus far suggest that intrauterine exposure poses the greatest risk, but more recent reports have reopened speculation that infection could occur at or around the time of delivery. The prospects for intervention, to stop transmission from mother to child, rest on the ability to identify HIV-infected women; the knowledge of how and when the virus infects the fetus; and how to identify, as early as possible, those truly infected infants. Resources should therefore be set aside for routine screening for HIV in antenatal women. There is also a need to quantify the contribution made by intrauterine versus intrapartum events. Lastly, promising new techniques designed to detect neonatal HIV infection must be properly evaluated against standard methods, and correlated with clinical outcome. Only then can the efficacy of antiretroviral therapy be tried, to prevent vertical transmission. PMID- 1633663 TI - Burn rehabilitation and reconstruction. PMID- 1633664 TI - Burn rehabilitation: dimensions of the problem. AB - Recent improvements in the mortality rates of burned patients are attributed to the expansion of specialized burn centers. Satellite treatment areas with trained personnel need to be developed, located away from the burn center, and efforts should be made to increase the number of patient programs at existing burn centers. In addition, studies need to be conducted on cost consequences, hypertrophic scarring, peripheral and central nervous system involvement, musculoskeletal changes, sleep deprivation, and the comparison of various treatment techniques to determine what protocols provide the best treatment outcome. PMID- 1633665 TI - The cost of burn care and the federal government's response in the 1990s. AB - This article attempts to predict the federal government's response to the cost of burn care in the 1990s by examining the explosive growth of health care costs in the 1980s and the impact that this had on hospitals with burn centers. The Prospective Payment System (PPS) was enacted in 1983, which limited the government's liability to hospitals by effectively capping the amount of federal dollars in the system. The inequities of the classification of burn patients by the PPS is discussed and a proposal for modification is outlined. PMID- 1633666 TI - Rating burn impairment. AB - We have described the method of rating impairment published by the American Medical Association (AMA) and the method requested by the Social Security Administration (SSA). For various reasons it will be some time before burn centers will be able to report impairment as easily as they now report length of stay and other parameters, but in time it will come. When it is possible, the methods used will probably not be identical with the AMA method nor the SSA method described previously. But whatever method is used, it will surely incorporate concepts from each and portions of each--and the two exist and are used right now. Therefore, it is useful for burn physicians to understand the two methods and be prepared to use either. PMID- 1633667 TI - Reintegrating the healed burned adult into society: psychological problems and solutions. AB - This article reviews important psychosocial factors that effect reintegration of the burned patient into society. Issues of pain, brain injury, the psychological reaction, posttraumatic stress, the impact on the family, and alcohol and substance abuse are discussed, and possible solutions to these problems are offered. PMID- 1633668 TI - Helping the burned child to adapt. AB - Adaptation in burned children is multifaceted and complex due not only to etiologic variables but also to age-specific developmental issues and the level of family development. Parental and peer support are identified in the literature as major contributors to higher levels of self-esteem and adaptation. The potential for these levels of adaptation is complicated by the number of burn injured children residing in chaotic, dysfunctional families with limited ability to support psychosocial rehabilitation. Various interventions are presented as methods of addressing the social/emotional needs of higher-functioning patients and families. PMID- 1633669 TI - Ethical issues of burn management. PMID- 1633670 TI - Reconstructing the burned face. AB - The priorities, timing, techniques, and philosophies of reconstruction of the burned face are outlined in this article. Each anatomic area is analyzed, and the appropriate procedure is described. PMID- 1633671 TI - Ear reconstruction. AB - This article discusses both the surgical and nonsurgical management of the burned ear. Partial and total autologous reconstruction, as well as osseointegrated prosthetic reconstruction, are described. PMID- 1633672 TI - The thermally injured ear: a systematic approach to reconstruction. AB - The ears are special and unique structures that ordinarily are ignored during our daily routines. A thermal injury of relatively moderate proportions can irreparably alter their shape and appearance. Many reconstructive techniques have been garnered to restore these delicate structures. Herculean efforts will consistently fall short of these goals if tissue preservation is not in the forefront of our treatment protocol. Iontophoresis coupled with topical antimicrobial agents have been shown to ameliorate cartilage loss, allowing for delayed operative intervention, when more consistent results may be obtained. Early radical resection of ear soft tissue or structural cartilage should be an endeavor of last resort in all but a few instances, such as unresponsive suppurative chondritis. Segmental restoration of the injured ear allows for dismantling of the various parts to recreate the whole. A facsimile of the original is possible if the major visible distinguishing landmarks are salvaged. Flap resurfacing of exposed cartilage yields closer tissue match, color, and texture, and it affords a greater proclivity for survival than does graft closure. Sacrifice of the helical lip relegates the ear to that of a flat, less than-optimal appearance. Tissue expansion coupled with cutaneous flap closure will usually preclude this situation. Skin grafting is a valuable tool in our armamentarium but should be used judiciously in situations where graft coverage is either necessary or desired to produce enhanced results. In such instances, the thickness of the graft must be considered, ranging from an almost translucent quality for the antihelix to that of a much thicker graft for the helix. Application and direction of the graft will be determined by the underlying surface contours. Until the reconstruction has been completed, burn patients and their families usually do not view the injured ear that has been snatched from the fires of adversity. The unveiling frequently effects a felicitous atmosphere, because they perceive a relatively normal-looking ear. The final result is all that matters. PMID- 1633673 TI - Making the burned hand functional. AB - The goal of treatment of the burned hand is to make the hand functional at the conclusion of treatment. Function should ideally include both fine pinch and power grip but will ultimately be determined by the individual patient's needs. At no time, however, can the care of the burned hand be performed in a vacuum, losing sight of the patient as a whole. It must also be remembered that the hand functions as part of the upper extremity. Full hand motion is useless if significant contractures of the elbow or axilla prevent the patient from positioning the hand so that this motion can be utilized. Rehabilitation must render the entire extremity functional. Thus, it becomes obvious that a team effort is mandatory. This usually will include the following individuals: physician, nurse, occupational therapist, physical therapist, vocational rehabilitation counselor, and social worker. A functional upper extremity means that the goal must be to return patients to their preburn vocations and avocations. A clear understanding of job requirements and work habits will allow realistic goals to be established. However, when the goal of optimal function cannot be reached, early retraining will help to obtain optimal rehabilitation. PMID- 1633674 TI - The burned small finger. AB - Postburn deformities are common in the small finger. A boutonniere-like deformity may develop when no injury has been noted in the central slip of the extensor tendon. Attention to the anatomic differences of the fifth digit and principles of graft contraction make this deformity preventable. In the long-standing burn hyperextension deformity of the metacarpophalangeal joint, recurrence of the deformity may occur after reconstruction. Evaluation of extrinsic extensor tightness may indicate an alteration in the soft tissue-to-skeleton relationship. Composite tissue expansion of the tendon and overlying skin graft provides an alternative reconstruction method. PMID- 1633675 TI - Reconstruction of burns of the trunk and breast. AB - This article discusses the pathogenesis and reconstruction of hypertrophic scarring of the burned trunk. General reconstruction schemata are provided. Reconstruction of specific problems of the chest, abdominal wall, breasts, and perineum are also discussed. PMID- 1633677 TI - Splints and accessories following burn reconstruction. AB - Splints, exercise, traction, and compression garments are commonly accepted methods to minimize disabling scar formation. Although burn rehabilitation treatment has improved over the past 10 years, there is still no overnight cure for scars and contracture. The extent and depth of the burn injury, emotional strength and patience of the burn victim, and support systems available play an important role in scar treatment. Scar contracture is a frustrating complication for the recovering patient and burn team. Surgical reconstruction to correct functional impairment is often needed before wound maturation is complete. Splints are usually part of the postoperative treatment plan. When this is the case, patient understanding, compliance, motivation, and comfort are important to assure splint effectiveness. The treatments reviewed are specific for scar contracture limiting function of the upper body. Although they were presented as treatment of neck, mouth, axilla, and hand contractures, many of the principles and materials can be used after burn reconstruction of the lower extremities. Regardless of the area treated, assessment of patients is important to determine their specific needs in splint design. PMID- 1633676 TI - Reconstruction of the burned lower extremity. AB - Many of the long-term sequelae and deformities are preventable by early wound closure and aggressive physical managements. Concurrent and associated injuries and medical problems may place a patient with lower extremity burn injury into different clinical subsets. The standard care may have to be modified to accommodate these differences. The scars, the deformities, and the morbidity have decreased dramatically with early aggressive care and physical management. When contractures and deformities are recognized early in the rehabilitation phase, many of these can be satisfactorily corrected by physical means. If the contractures cause functional limitations, surgical release is indicated. The donor defects of free grafts or flaps should not be more deforming than the original injury. The goal is to return the patient to society as normal in function and appearance as possible. PMID- 1633678 TI - Pressure techniques for the prevention of hypertrophic scar. AB - No ideal or all-purpose method of scar control exists. Successful management of hypertrophic scar depends on early and aggressive treatment. The creative use of available products facilitates the production of a cosmetic and functional scar. Selection of the appropriate contact media will be influenced by the size, location, and depth of the injury; the scar's ability to tolerate shear and pressure; the availability of various products; and, most importantly, the patient's involvement in his or her own rehabilitation. The use of pressure is only one segment of the total rehabilitation of the thermally injured patient. Its use in conjunction with exercise, splinting, positioning, and reconstructive surgery allows an optimal level of function and cosmesis to be achieved. PMID- 1633679 TI - Skin care of the healed burned patient. AB - Many complications beset the skin formed over burn wounds, whether by primary re epithelialization or grafting techniques, and these can evolve over days to decades. Mechanisms by which re-epithelializations, reattachment, and remodeling may result in skin prone to blistering, dryness, itching, contact dermititis, photosensitivity, and hypertrophic changes relatively early in the course of healing are considered, and therapeutic approaches are discussed. Late development of benign and malignant lesions calls for long-term surveillance of the healed skin of burned patients. PMID- 1633680 TI - Antibodies to platelet glycoproteins in haemophiliacs infected with HIV. AB - The techniques of Western blotting and the monoclonal antibody specific immobilization of platelet antigen (MAIPA) assay were used to detect antibodies to platelet glycoproteins in 43 samples of serum from 23 anti-HIV positive haemophiliacs (8 with severe thrombocytopenia, 6 with moderate thrombocytopenia, and 9 with a normal platelet count), six anti-HIV negative haemophiliacs and ten controls. Antibodies were present in the majority of anti-HIV positive patients' sera even before the onset of thrombocytopenia. Thrombocytopenia was associated with an increase in the incidence of antibodies to GPIIIa and GPIb, whereas the antigen most frequently recognized in patients without thrombocytopenia was GPIIb. Anti-GPIIb and/or GPIIIa reactivity was also seen in three out of the six anti-HIV negative patients. There was no correlation between the absolute platelet count and the detection of antibodies in either assay. Effective therapy for thrombocytopenia with zidovudine, interferon or splenectomy did not influence the presence of antibody. Eight of nine patients with AIDS were negative in the MAIPA assay, consistent with their depressed immune status. It is concluded that the production of antibodies to platelet membrane glycoprotein in anti-HIV positive haemophiliacs is influenced by factors other than HIV. The presence of such antibodies is independent of the platelet count and is therefore unlikely to play a causative role in HIV-related thrombocytopenia. PMID- 1633681 TI - Antigen expression of frozen platelets. AB - Platelet antigens of platelet samples from 36 donors, frozen for different intervals, were evaluated by the platelet suspension immunofluorescence test (PSIFT). A, B, PLA1(HPA-1a) and various HLA antigens were tested by their corresponding antisera. The antigen could be detected in almost all the samples after one month of freezing. After 3 and 6 months, the platelet antigens could only be detected in 29.2% and 3.7% of the samples, respectively. There was no difference in decay of antigen expression among A, B, PLA1 and HLA antigens. When compared with the freshly prepared platelets, frozen platelets presented stronger antigen expression after 2 to 4 weeks of storage. This may suggest that the frozen platelets could be used for platelet crossmatching procedures without loss of their antigenicity within one month. PMID- 1633682 TI - Successful use of liposome encapsulated amphotericin to treat invasive aspergillosis following failure of conventional amphotericin. AB - We describe a case of proven invasive pulmonary aspergillosis in a neutropenic patient in whom disease progression occurred during treatment with conventional amphotericin B despite neutrophil recovery. Treatment with liposomal encapsulated amphotericin B resulted in clinical and radiological improvement and the clearance of aspergillus spores from the sputum. PMID- 1633683 TI - The selection of laboratory equipment. AB - The last few years have seen dramatic changes in laboratory haematology. Technological developments with increasing levels of automation have resulted in a plethora of new instruments. The choice of which to buy, often confused by conflicting advice and persuasive salesmanship, must be balanced by the need for cost containment. This calls for an understanding of the principles of selection to ensure that the system that is chosen will provide reliable results in the most efficient manner at the lowest possible cost. Most of the instruments which are currently available perform their intended tasks reasonably well albeit with some inter-instrument differences, usually due to different operating procedures and different methods of calibration. The task is to find a system that performs the required tests correctly and reliably, fits into the work requirements of the laboratory and is accepted by the staff who will operate it, whilst its cost both capital and recurrent, should be within the department's financial constraints. The selection of laboratory equipment is thus a complex and time consuming task. PMID- 1633684 TI - In vitro effects of ethanol on the phagocytic and microbial killing activities of normal human monocytes and monocyte-derived macrophages. AB - Human blood monocytes were cultured within the wells of chamber slides in growth medium to which 0, 1, 2, or 3 mg ethanol per ml was added at the start of the culture. After incubation for 1 h, 1 day and 7 days, their ability to phagocytoze IgG-sensitized red cells and to phagocytoze and kill non-opsonized Candida albicans was assessed. In all alcohol-containing wells, the concentration of alcohol in the growth medium fell progressively, reaching negligible values after 3 days. When compared with control cells, monocytes incubated with 1, 2 or 3 mg ethanol/mg for 1 h showed impaired phagocytosis of IgG-sensitized RBC and non opsonized C. albicans and those incubated with 1 or 2 mg ethanol/ml for 1 h showed impaired killing of Candida. After incubation for 7 days, the monocyte derived macrophages in wells initially containing 1, 2 or 3 mg ethanol/ml showed increased phagocytic activity towards C. albicans but not towards sensitized RBC. In addition, in 4 of 5 experiments, the percentage of phagocytozed organisms killed was increased in wells initially containing 1 mg ethanol/ml. The results support the view that the susceptibility of chronic alcoholics to certain infections may be partly dependent on an ethanol-induced depression of the phagocytic and killing functions of macrophages. They also suggest that a few days after a brief period of exposure to ethanol there may be stimulation of certain but not all effector functions of macrophages. PMID- 1633685 TI - Diffuse intracerebral involvement in B-cell chronic lymphocytic leukaemia. A case report. PMID- 1633686 TI - Vacuolated Burkitt-like cells in adult T-cell leukaemia/lymphoma. PMID- 1633687 TI - Clostridium perfringens septicaemia and massive intravascular haemolysis as a terminal complication of autologous bone marrow transplant. PMID- 1633688 TI - Myelodysplastic syndrome with t(8; 12) (q22; q13) translocation. PMID- 1633689 TI - RDW in vitamin B12 and folate deficiency and in patients with alcohol-related macrocytosis. PMID- 1633690 TI - Survival in adult leukaemia. AB - The evaluation of treatment and outcome in adult leukaemia requires unselected data. Such data is available from one Health Region in the United Kingdom with an adult population of 3.1 million. In the period July 1982 to December 1989, 676 cases of acute myeloid leukaemia (AML), 136 of acute lymphoblastic leukaemia (ALL) and 141 of chronic granulocytic leukaemia (CGL) were registered. The median survival for AML was 21 weeks and 26% of these patients died within 4 weeks of diagnosis. For ALL, the corresponding figures were 81 weeks and 21%. In CGL, the median survival was significantly different for males and females: 113 weeks and 173 weeks respectively. The 5-year survival in AML was 9%, in ALL, 31% and in CGL, 29% (20% for males, 45% for females). Age at presentation was the single most powerful prognostic factor and probably accounts for survival differences between patients referred to tertiary centres and those treated in district general hospitals. (DGH). Survival may be improving overall as supportive care improves. PMID- 1633691 TI - [Nightingale's perspective of nursing administration]. PMID- 1633692 TI - [The Nightingale nurses: the myth and the reality]. PMID- 1633693 TI - [A round-table talk: Florence Nightingale; the woman who lived in the reality]. PMID- 1633695 TI - [History and education of nursing as seen in 'Kyoiku Zasshi (Education Periodical)]. PMID- 1633694 TI - [Superintendent's quarterly reports to the Governors of Nursing Home at Harley Street, 1853-4]. PMID- 1633696 TI - [Asking about 'nursing and medicine']. PMID- 1633697 TI - [The world of Hildegard von Bingen]. PMID- 1633698 TI - [What is psychiatry?]. PMID- 1633699 TI - [Searching for logic of children's recognition]. PMID- 1633700 TI - Contact dermatitis in hairdressers' clients. AB - The aim of our study was to report the frequency of sensitization to hairdressing allergens in a group of patients with contact dermatitis, in whom previous treatments with hair dyes or permanent wave solutions were suspected to be the cause. 49 of 261 hairdressers' clients (18.7%), who were patch tested with the hairdressers' screening series in the years 1985-1990, showed one (27) or more (22) positive reactions to hairdressing chemicals. This study confirms hair dyeing to be the procedure associated with the highest risk of sensitization among hairdressers' clients. Among hair dye allergens, PPD is the most frequent sensitizer (7.3%). A low rate of sensitization to the PPD derivatives PAP, ONPPD and PTD was detected in these clients, there being no differences in the frequency of sensitization to the 3 substances (4.2%, 4.6% and 4.6%, respectively). Only 0.4% of clients were positive to resorcinol, while pyrogallol showed a 2.3% rate of sensitization. Sensitization to GMTG was found in 3.3% of patients. ATG was an infrequent sensitizer (1.1%). Allergic contact dermatitis due to APS is quite rare (2.7%), in view of the widespread use of this compound. A positive open patch test in 1 hairdressers' client, who complained of generalized urticaria after hair bleaching, confirmed the diagnosis of immediate contact reaction due to APS. Sensitization to hairdressing allergens among consumers (18.7%) is possibly more frequent than sensitization to other cosmetic ingredients. We previously detected a 14.3% rate of sensitization to cosmetic ingredients in patients with suspected allergic contact dermatitis caused by cosmetics. On the other hand, reactions to cosmetic ingredients were also common in our patients. This may indicate that hairdressers' clients make greater use of cosmetics than average. PMID- 1633701 TI - Allergic contact dermatitis in children. A multicenter study of the Portuguese Contact Dermatitis Group (GPEDC). AB - The authors report a study of allergic contact dermatitis in 329 Portuguese children of 14 years or younger. 170 children (64 male and 106 female) reacted to 1 or more allergens. Most of these were in the 11-14 years group. The main allergens were nickel, thimerosal, cobalt, mercury, fragrance-mix and potassium dichromate. Nickel reactivity predominated in females over the whole group, but a greater number of males younger than 5 years reacted to nickel. The number of positive reactions increased with age, but this was not accompained by an increase in the % of relevant tests. 12 children, all of them 13 or 14 years-old, had an occupational allergic contact dermatitis. PMID- 1633702 TI - Effect of a new topical cyclosporin formulation on human allergic contact dermatitis. AB - We studied the effect of a new topical cyclosporin (CS) formulation on the suppression of allergic contact dermatitis. 4 test sites were outlined on the back of healthy male volunteers. For 7 consecutive days, the test sites were treated as follows: #1: CS formulation (10%), #2: placebo formulation, #3: flumethasone pivalate (FP) formulation (0.02%; #4: no treatment. On day 8, we challenged all test sites in the diphenylcyclopropenone (DCP) sensitized individuals. Photographic and clinical documentation was performed daily. 24 h after the DCP skin challenge, a marked redness accompanied by severe itching and slight pain occurred in the test sites pretreated with CS (#1) and placebo (#2). A considerably milder reaction was noted in the untreated test site (#4) and only a faint redness was noted in the test site pretreated with FP (#3). After 36 h, a further increase in the cutaneous reaction was documented in CS and placebo pretreated test sites (#1, 2). In agreement with other workers, topical CS did not suppress experimentally-induced allergic contact dermatitis in man. On the contrary, in CS and placebo pretreated areas (#1, 2), an increased cutaneous reaction was observed. This observation may be explained by the extensive pretreatment with the topical formulation of CS and placebo, which possibly caused a profound perturbation of the stratum corneum, enabling excessive allergen penetration compared to the untreated area with intact stratum corneum. PMID- 1633703 TI - Comparative evaluation of permeation testing of protective gloves to solvents: in vitro in permeation cells versus in vivo in guinea pigs. AB - Most current data on the protective effect of gloves against chemicals are obtained in vitro, using permeation cells. In vivo testing would give additional information on efficiency but is both expensive and time-consuming. It would therefore be valuable to know whether any definitive relationship exists between results obtained in vivo and in vitro. Gloves of natural rubber, butyl rubber and polyvinyl chloride (vinyl) were tested against 3 organic solvents, toluene, 1,1,1 trichloroethane and butanol, in vivo in guinea pigs and in vitro in permeation cells. Breakthrough times, absorption rates and steady state permeation rates were determined and compared on a relative basis. Some of the gloves that had a low degree of resistance to the test solvent in vitro nevertheless showed a rather good reducing capacity on the percutaneous absorption in vivo. However, for 2 gloves where no breakthrough was noted for butanol in vitro, permeation occurred at a degree lower than the minimum detection level. At this low concentration, the solvent was not absorbed through intact skin but through damaged skin. The breakthrough times for the 3 solvents corresponded well for the 2 test systems. The relative absorption rates and relative steady-state permeation rates varied considerably and no definitive relationship between the 2 sets of test results could be seen. PMID- 1633704 TI - Contact urticaria from dog saliva. PMID- 1633705 TI - Guitar-string dermatitis. PMID- 1633706 TI - False positive reaction to patch testing with aqueous mercuric chloride in an aluminum Finn Chamber. PMID- 1633707 TI - An unusual late reaction to PTBP. PMID- 1633708 TI - Nickel in jewellery and associated products. PMID- 1633709 TI - Compositae dermatitis: a survey. AB - Compositae dermatitis in an allergic contact dermatitis, frequently chronic, triggered by plants of the Compositae family. The condition, which is seen, in particular, in middle-aged and elderly persons, typically starts in the summer months with an acute eczema either corresponding to areas exposed to light and air, or corresponding to areas of plant contact; it disappears spontaneously during the fall of the year. Repeated exposure over a number of years may cause severe intractable dermatitis affecting the patient throughout the year. The responsible allergens are sesquiterpene lactones, and investigations to date indicate that the frequency of the allergy is similar to that seen with some of the contact allergens of the standard patch test series. The diagnosis, however, is difficult, partly due to the fact that the clinical picture may be mistaken for a photodermatosis, and partly owing to the difficulty in obtaining commercially available allergens for patch testing. The diagnosis is therefore based on testing with plant extracts, which can cause pronounced local reactions and possibly active sensitization. A survey is given of the possible modes of sensitization, sex and age distribution, the relationship to photosensitivity and atopy, as well as the possible treatment. It is concluded, on the basis of the chronic nature of the disease, and the diagnostic and treatment problems, that continued intensive research into the condition is urgently needed. PMID- 1633710 TI - The molecular genetics of autosomal-dominant polycystic kidney disease of the PKD1 type. PMID- 1633711 TI - Isolation and characterization of a candidate gene for autosomal-dominant polycystic kidney disease. PMID- 1633712 TI - MEGABASE/PKD: a genetic database for polycystic kidney disease. PMID- 1633713 TI - Genetic heterogeneity of polycystic kidney disease in Europe. PMID- 1633714 TI - Regulation of cell proliferation and fluid secretion in the progressive enlargement of renal cysts. PMID- 1633715 TI - Pathophysiology of renal tubular cyst formation in murine models of polycystic kidney disease. PMID- 1633716 TI - Rat models of polycystic kidney disease. PMID- 1633717 TI - A chimaeric mouse model for autosomal-dominant polycystic kidney disease. PMID- 1633718 TI - Polycystic kidney disease: thoughts on the meaning of prevention. PMID- 1633719 TI - Effect of a low-protein diet on the rate of progression of chronic renal failure in patients with polycystic kidney disease. PMID- 1633720 TI - Therapeutic effects of hidrosmin on chronic venous insufficiency of the lower limbs. AB - A double-blind, placebo-controlled trial was carried out to assess the effectiveness of a new synthetic bioflavonoid, hidrosmin, in patients with chronic venous insufficiency of the lower limbs. Fifty-seven patients, showing varicose veins and ankle swelling and suffering from local pain and heaviness of the legs, were allocated at random to receive treatment for 45 days with 1 capsule 3-times daily of either 200 mg hidrosmin (30 patients) or placebo (27 patients). Pain and heavy legs were assessed using rating scales; swelling was assessed by a photographic method. The results showed that hidrosmin produced a significant clinical improvement in all of the parameters evaluated; compared with placebo, there was a marked reduction in the main subjective symptoms accompanied by a 10% reduction in swelling. Apart from 1 patient who complained of epigastric pain, there were no reports of adverse events during the study period. PMID- 1633721 TI - Cefetamet pivoxil in community-acquired pneumonia: an overview. AB - A total of 305 patients with community-acquired pneumonia have participated in comparative or non-comparative studies involving cefetamet pivoxil. Of these, 211 (55 adults and 156 children) were involved in a series of open, prospective, comparator-controlled, multi-centre studies. Adults were randomized to receive either cefetamet pivoxil 1000 mg twice daily or amoxycillin 750 mg 3-times daily for 10 days. Children received either cefetamet pivoxil 10 mg/kg twice daily, cefetamet pivoxil 20 mg/kg twice daily or cefaclor 10 mg/kg 3-times daily for 7 to 8 days. The remaining 94 patients were treated openly with cefetamet pivoxil, with most patients receiving cefetamet pivoxil 500 mg twice daily for an average of 10 days; an elderly sub-group of these patients aged 70 to 103 years received therapy for an average of 11 days. The main causative organisms isolated were Streptococcus pneumoniae and Haemophilus influenzae. In adult patients, a successful clinical outcome was achieved in 100% of assessable patients receiving cefetamet pivoxil 1000 mg twice daily, and about 90% in those receiving 500 mg twice daily. The success rate in children was 98% for both dose levels of cefetamet pivoxil and 90% for those receiving cefaclor. In elderly patients, the percentage was 78% for the 500 mg twice daily patients. Thus, the standard dose of cefetamet pivoxil (500 mg twice daily in adults, 10 mg/kg twice daily in children) was well tolerated and proved to be at least as effective as the comparator drugs which were given 3-times a day. PMID- 1633722 TI - Efficacy and tolerability of enteric-coated naproxen in the treatment of osteoarthritis and rheumatoid arthritis: a double-blind comparison with standard naproxen followed by an open-label trial. AB - One hundred and twenty-three patients with osteoarthritis (n = 50) or rheumatoid arthritis (n = 73) were enrolled in a 6-week, double-blind, randomized, controlled, parallel trial comparing enteric-coated naproxen with standard naproxen. Ninety-eight patients subsequently entered a 20-week, open-label trial of enteric-coated naproxen. The study demonstrated that naproxen in both its standard formulation and its new enteric-coated formulation is a highly effective form of therapy for osteoarthritis and rheumatoid arthritis. The tolerability profiles of the two formulations were similar in terms of the types of complaints reported. It is concluded that enteric-coated naproxen is an efficacious and well tolerated formulation for the treatment of osteoarthritis and rheumatoid arthritis. PMID- 1633723 TI - Open-label tolerability study of enteric-coated naproxen in the treatment of osteoarthritis and rheumatoid arthritis. AB - Two hundred and ninety-six patients were enrolled in a 6-month, open-label tolerability study of enteric-coated naproxen in patients with rheumatoid arthritis (n = 174) and osteoarthritis (n = 122). Thirty percent of the patients were greater than 65 years of age. Under standard clinical prescribing conditions, enteric-coated naproxen 500 mg twice daily and 375 mg twice daily demonstrated an acceptable tolerability profile that was not different from what one would expect with standard naproxen. PMID- 1633724 TI - The efficacy of pre-operative controlled-release indomethacin in the treatment of post-operative pain. AB - A double-blind, placebo-controlled study in patients undergoing lumbar laminectomy was carried out to assess the morphine-sparing effect of a controlled release indomethacin formulation ('Flexin Continus' tablets, 75 mg). Thirty patients were randomly allocated to receive 1 tablet of active or placebo study medication pre-operatively and their pain scores on visual analogue scale (VAS) and their morphine consumption, delivered by Patient Controlled Analgesia (PCA), were recorded over the 24-hour post-operative period. Over the first 4-hour post operative period, the patients who had received active treatment reported less pain on VAS than those in the placebo group and this difference was statistically significant on recovery (p = 0.033) and at 1 hour post-recovery (p = 0.013). By 4, 8, 12 and 24-hours post-recovery the mean cumulative amount of morphine used by patients in the active treatment group was reduced by 25%, 23%, 37% and 30%, respectively, compared to the control group. At the 12-hour time point, the difference in morphine consumption approached statistical significance (p = 0.074). It is concluded that the pre-operative administration of controlled release indomethacin reduces post-operative morphine requirements and significantly reduces VAS pain scores on recovery. PMID- 1633725 TI - Non-random distribution of abnormal mitoses in heteroploid cell lines. AB - We have performed absorption-cytometric DNA measurements of the DNA contents of the G0/G1, G2, metaphase, and telophase cells of the heteroploid MCa-11 and HL-60 lines, as well as the WCHE-5 line which has a narrowly restricted number of chromosomes. We found that morphologically unbalanced mitoses occurred much more frequently in telophase-cell pairs of the heteroploid MCa-11 and HL-60 lines than in those of the chromosomally stable WCHE-5 line. Furthermore, the morphologically unbalanced mitoses represented unequal segregation of DNA into each of the daughter telophase nuclei. Such mitotic segregation errors (MSE) occurred almost exclusively in telophase cells with DNA contents which were above, or below, the DNA content of the modal telophase population. The net effect of these non-random, unblanced divisions of heteroploid cells with non modal DNA contents is to produce one daughter cell with a DNA content that tends to return to the modal DNA content peak. PMID- 1633726 TI - Semi-automated detection of aberrant chromosomes in bivariate flow karyotypes. AB - A method is described that is designed to compare, in a standardized procedure, bivariate flow karyotypes of Hoechst 33258 (HO)/Chromomycin A3 (CA) stained human chromosomes from cells with aberrations with a reference flow karyotype of normal chromosomes. In addition to uniform normalization of normal and abnormal flow karyotypes, the main purpose is detection of structurally abnormal chromosomes in often complex karyotypes of tumor cells. The method, which has been implemented in a computer program, consists of a comparison of individual chromosome peaks with the positions of peaks in the flow karyotype constituted by normal chromosomes and takes into account the natural variability in base composition of normal chromosomes among healthy individuals. Flow-karyotypes are normalized using an iterative fitting procedure, using corrections for (1) amplification of HO and CA fluorescence, (2) cross-talk between the fluorescence signals of HO and CA, and (3) offset of the HO and CA origin. Flow karyotypes of two cell lines, one with a simple deletion and the other with more complex karyotypic changes, were analyzed. The results of flow analysis were found to be in general agreement with the cytogenetic analysis of quinacrine banded karyotypes. PMID- 1633727 TI - Influence of different cell extraction methods on cytometric features. AB - The purpose of this study was to investigate the influence of different cell extraction procedures on relative nuclear DNA content (IOD), nuclear area, and texture features of Feulgen-stained nuclei. In imprints and smears of fine-needle aspirates and suspensions from one human liver specimen, 50 diploid, 50 tetraploid, and 25 octaploid nuclei were measured from each slide. In addition, for DNA measurements, the progressive mean of IOD and tetraploid/diploid and octaploid/diploid ratios was calculated. The results show that the progressive mean of the IOD is constant after measuring 25-30 nuclei. For the three types of specimens, the IOD of diploid nuclei varied slightly. The average coefficient of variation was about 5% for the fine-needle aspirates, imprints, and suspensions. For all tissue sampling methods, the 99% confidence limits of the tetraploid/diploid ratio and octaploid/diploid ratio were within the range of 1.9 2.1 and 3.7-4.3, respectively. The nuclear area and most of the texture features showed a significant difference (p less than 0.01) between the three sampling methods in all nuclear populations. In conclusion, different tissue sampling methods have little or no effect on DNA-related IOD measurements, whereas the outcome of nuclear area and texture features is very dependent of the cell extraction procedure. PMID- 1633728 TI - A quantitative method for evaluating bivariate flow cytometric data obtained using monoclonal antibodies to bromodeoxyuridine. AB - A method is presented for analyzing data from bivariate analysis of cell populations exposed to bromodeoxyuridine and subsequently examined both for the presence of BrdUrd and for the cellular DNA content. It is shown that certain features may be defined in the bivariate data which are constant independent both of cell type and, within limits, experimental variability. These landmark features include the ratio of red, DNA, fluorescence of G2 + M cells to G1 cells, the ratio of green fluorescence corresponding to the non-specific binding of unlabeled G2 + M cells to unlabeled G1 cells, and the distribution of green fluorescence in unlabeled cells. The landmarks make it possible to standardize rules for establishing the separation line between-labeled and unlabeled cells as required in these experiments to obtain estimates of cytokinetic parameters. Values obtained for the DNA synthesis time and the potential doubling time which result from different decision rules for distinguishing labeled from unlabeled are compared in two murine tumor lines. The potential doubling time, but not the DNA synthesis time is shown to depend sensitively on the separation line. Suggestions are presented for analyzing clinical data with this procedure. PMID- 1633729 TI - Flow cytometric detection of the mitochondrial BCL-2 protein in normal and neoplastic human lymphoid cells. AB - The bcl-2 proto-oncogene, rearranged and deregulated in B-cell lymphomas bearing the t(14;18) translocation, encodes an inner mitochondrial membrane protein that blocks apoptotic cell death. We have developed a sensitive immunofluorescence assay for the single- and multicolor flow cytometric analysis of bcl-2 protein in relation to other markers and cell cycle, based on a fixation-permeation step of cells with paraformaldehyde and Triton X100 and the use of a bcl-2 specific monoclonal antibody (MoAb). As an application of this method, we have examined the expression of bcl-2 in normal and neoplastic lymphoid cells. We have found that greater than 80% of normal T-and B-cells are bcl-2 positive; following in vitro mitogen activation, the bcl-2 reactivity decreased slightly in the former but markedly in latter cells. In both cases the bcl-2 expression was not restricted to a specific phase of the cell cycle, as evidenced by two-color analysis. On lymphoblastoid cell lines, the bcl-2 staining intensity was variable and not necessarily correlated to molecular rearrangements of the bcl-2 gene. Among fresh B-cell non-Hodgkin's lymphomas (B-NHL), most sporadic Burkitt's cases were bcl-2 negative. Of four centroblastic-centrocytic cases with rearrangements of the bcl-2 gene, only two presented elevated amounts of bcl-2 protein, indicating that the levels of bcl-2 are not diagnostic of the translocation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1633730 TI - Flow cytometric analysis of opposite effects of a monokine on proliferation and differentiation of murine B lymphocytes. AB - A 35,000 mw factor able to replace macrophages (FRM) in the induction of the in vitro antibody response to sheep erythrocytes has been isolated from the supernatant of murine resident peritoneal macrophage cultures. Purified FRM, when added at the outset of cultures, induced B cells to generate an antigen-specific antibody response. The signals provided by FRM in the process of B cell activation were analyzed using a polyclonal model. Cell cycle analysis by multiparameter flow cytometry after acridine orange staining showed that FRM, on its own, did not trigger the transition of B cells from the G0 to the G1 stage of the cell cycle. In addition, FRM affected neither the basal intracellular free calcium level ([Ca2+]i) nor the rapid increase in [Ca2+]i induced by crosslinking of membrane immunoglobulin (mIgM) with anti-mu antibodies. In parallel with its positive effect on B cell differentiation, FRM markedly reduced both proliferation and cell cycle progression of B cells stimulated with anti-mu plus interleukin 4 (IL-4). Indeed, the addition of FRM to such cultures led to a preferential accumulation of cells in the early G1 compartment of the cell cycle and to a decreased frequency of cells in all other phases including G1B, S and G2/M. PMID- 1633732 TI - NADH-dependent dehydrogenase activity estimation by flow cytometric analysis of 3 (4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. AB - MTT reduction is usually analysed by colorimetric assay to study mitochondrial dehydrogenase activity as a test of cytotoxicity. This enzymatic reaction produces dark-blue granules of formazan, which increase cell refringency. In this work, we define the conditions for MTT use in quantitative flow cytometric analysis. MTT reduction provides a non-fluorescent dye usable by this technique to study an intracellular NADH-dependent dehydrogenase activity in vital cells. We observe that formazan production increases asymptotically with cell concentration and that this temperature-dependent Michaelis enzymatic reduction is produced essentially by mitochondrial dehydrogenases. In isolated mitochondria from rat hepatocytes and in whole L1210 murine leukemia cells, the Michaelis constants (KM) observed in the presence of respiratory substrates were, respectively, 10 microM and 500 microM. The inhibition of mitochondrial protein synthesis by chloramphenicol, which induces a rise of MTT reduction due to the correlative stimulation of glycolysis (Pasteur effect), is a limit of the MTT assay as a cytotoxicity test. PMID- 1633731 TI - Seric factors influence cell cycle modifications during commitment of murine erythroleukemia cells to differentiation. AB - Cell cycle modifications are among the early events which take place during the induced differentiation of murine erythroleukemia (MEL) cells; a transient accumulation of the cells in the G1 phase of the cell cycle, followed by a re entry of the cells into a proliferation state, has been described. In order to characterize a putative role of serum in such variations, we have studied the modifications of the cell cycle parameters when cells were induced to differentiate in the presence or in the absence of seric factors. We show that, in the absence of exogenous factors brought by serum, the G1 accumulation was enhanced both in amplitude and in duration, but cells were still able to bypass the G1 block and re-enter into the S phase. These results indicate that the resumption of cell proliferation after the transient block is under synergistic control of seric and endogenous factors, but these later are sufficient to overcome the block. However, MEL cells were unable to differentiate in the absence of seric factors, as measured by the number of benzidine-positive cells during induction with hexamethylene-bisacetamide (HMBA) or butyric acid. This capacity to differentiate was recovered when serum was added back to the culture medium, and the efficiency of recovery was maximal when cells underwent a full round of DNA replication in the presence of serum after the G1 block. The analysis of two molecular markers of cell differentiation confirmed these results. PMID- 1633733 TI - Aggregation of Escherichia coli B/r A during agar filtration: effect on morphometric measurements. AB - We have investigated the phenomenon of particle aggregation in a sample of 71,038 Escherichia coli B/r A cells in balanced exponential growth, during preparation for electron microscopy by agar filtration. The bacteria were photographed in a transmission electron microscope and the dimensions and spatial relationships among all the members of each aggregate were recorded using an interactive image processing system. The proportion of aggregated cells, 22%, is much greater than that found by direct count in a light microscope (7%), implying that most aggregation takes place during the preparation stages. The aggregated cells are about 1% narrower than the free cells, because of mutual compression, and 1.5% longer, because of a selection bias in favor of longer cells. From a statistical analysis of the data, we conclude that the clustering of cells into aggregates in the course of sample preparation is the result of random encounters during the settling on the collodion membrane and of the changing surface tension during the drying process. A method is proposed to correct morphometric measurements for the distortion caused by cellular aggregation of this kind. PMID- 1633734 TI - Method to improve the sensitivity of flow cytometric membrane potential measurements in mouse spinal cord cells. AB - We have developed a technique to improve the sensitivity of relative membrane potential measurements in mouse spinal cord cells using the fluorescent, anionic, voltage sensitive dye, DiBa-C4(3) (Oxonol) and flow cytometry. In order to attribute cellular fluorescence primarily to membrane potential, signal variability due to cell size and shape was reduced by dividing the log fluorescence signal from each cell by either its log forward angle light scatter or log side scatter signals. The use of these ratios in place of log oxonol fluorescence reduced the coefficient of variation of the distributions while leaving the changes in mean fluorescence largely unaffected. Kolmogorov-Smirnov analysis of pre- vs. postkainate stimulation (an excitatory amino acid) showed improved sensitivity of the assay with the use of this ratio technique. PMID- 1633735 TI - On the measurement of cytokinetics by continuous labeling with bromodeoxyuridine with applications to chick wing buds. AB - The cytokinetic properties, specifically the phase-transit times, TG1, TS, and TG2+M, of chick wing bud cells were estimated using data obtained from continuous labeling of stage 20 embryos with bromodeoxyuridine (BrdUrd). The presence of BrdUrd was detected with monoclonal antibodies, and the amount of DNA in the cells was determined with propidium iodide. The fraction of cells in each cell cycle phase, the fraction of labeled cells, and the relative movement, a measure of the mean DNA content, of all labeled cells were evaluated using bivariate flow cytometry at successive times following introduction of the label. Equations are presented to describe the fraction of unlabeled cells in G2 + M, which gives a direct estimate of TG2+M; the fraction of all labeled cells, which can then be used to estimate TG1; and, finally, the relative movement, which provides an estimate of TS. Thus, the data measured in these experiments together provide estimates of the progression through the cell cycle of limb mesoderm cells. PMID- 1633736 TI - Some new aspects on adipose tissue development. PMID- 1633737 TI - T-cell cloning in human type I diabetes. PMID- 1633738 TI - Autoimmune diabetes mellitus in the BB rat. PMID- 1633739 TI - Platelet function in diabetes mellitus. PMID- 1633740 TI - The pharmacology of diabetic neuropathy. PMID- 1633741 TI - Electrophysiologic findings in optic nerve dysfunction associated with multiple evanescent white-dot syndrome. AB - Electrophysiologic findings in a case of multiple evanescent white-dot syndrome were studied. A 37-year-old woman presented with multiple white dots, granularity of the macula, and optic disc swelling in her left fundus. The electroretinogram and electro-oculogram revealed abnormal findings indicative of changes in the retinal pigment epithelium and photoreceptors. In addition, relative afferent pupillary defect, enlargement of the blind spot, a decrease in the critical fusion frequency, staining of the optic disc on fluorescein angiography and prolonged latency of the P100 component with decreased amplitude in pattern reversal visual evoked cortical potential strongly suggested dysfunction of the optic nerve in this patient. PMID- 1633742 TI - Clinical and ERG data in a family with autosomal dominant RP and Pro-347-Arg mutation in the rhodopsin gene. AB - In a family with autosomal dominant retinitis pigmentosa, documented over six generations, a previously undescribed point mutation in the rhodopsin gene could be identified. The mutation found in the six affected members examined but in none of the controls, including healthy members of the family, was a point mutation in codon 347 predicting a substitution of the amino acid arginine for proline, designated Pro-347-Arg. Six affected members from two generations were examined clinically and with ganzfeld rod and cone electroretinography. The cone and, more dramatically, the rod electroretinograms were reduced to residual b wave amplitudes or were non-detectable as early as ages 18 to 22 years. The Pro 347-Arg mutation resulted in a subjectively and clinically homogeneous phenotype: early onset of night blindness before age 11, relatively preserved usable visual fields until about age 30, blindness at ages 40 to 60, and change from an initial apparently sine pigmento to a hyperpigmented and atrophic fundus picture between 30 and 50 years of age. PMID- 1633743 TI - Electrophysiologic evaluation of the visual pathway in children. Case reports. AB - Clinical findings and results of electrophysiologic evaluation of the visual pathway were studied in seven children ranging in age from 10 months to 13 years. Using skin electrodes for electroretinographic and visual evoked potential testing, we obtained reliable results without sedation or pupil dilation. The half-field stimulation was indispensable for localizing lesions along the visual pathway and thus for specific diagnosis. PMID- 1633744 TI - Pattern electroretinogram as a function of spatial frequency after retrobulbar optic neuritis. AB - Steady-state (8-Hz) pattern electroretinograms in response to counterphased sinusoidal gratings of variable spatial frequency (0.6-4.8 c/deg) were recorded in 17 patients who had had retrobulbar optic neuritis in one or both eyes (23 eyes with a clinical history of optic neuritis) and in 21 age-matched normal subjects. Amplitude and phase of the Fourier-analyzed pattern electroretinogram second harmonic were measured. The mean pattern electroretinogram amplitude of patients was significantly reduced compared with that of controls. Amplitude reductions were more marked at intermediate (1-1.4 c/deg) than at lower or higher spatial frequencies. Therefore, the average amplitude versus spatial frequency response function differed significantly in patients compared with controls, displaying a lowpass instead of a band-pass shape. No significant differences in the mean pattern electroretinogram phase were observed between groups at any spatial frequency. These results indicate spatial frequency-dependent abnormalities in the pattern electroretinogram amplitude after optic neuritis, suggesting a specific loss of retinal neurons sensitive to stimuli of intermediate spatial frequencies. PMID- 1633745 TI - Empiric limits of rod photocurrent component underlying a-wave response in the electroretinogram. AB - The corneally recorded rod photocurrent component (photoresponse) underlying the a-wave feature of the electroretinogram was analyzed. The results set empiric limits on critical photoresponse variables. Measurements were obtained from four normal adult subjects on a-wave amplitude, a-wave velocity, b-wave amplitude, b wave implicit time and b-wave height above baseline. At high intensity, interference from the b-wave component was minimized and the amplitude of the saturated photoresponse component was approximated by the a-wave feature. At lower intensities, the a-wave feature represented progressively less of the underlying photoresponse amplitude. Photoresponse amplitude saturation was signaled by the abrupt slowing of the rate of decline of b-wave peak latency and occurred at an intensity about 2.5 log units above the first appearance of the b wave. At the intensity of photoresponse saturation, the peak amplitude of the a wave feature was only about 25% of the maximum amplitude of the underlying photoresponse component. A-wave leading edge velocity was found to increase up to 3 log units above the intensity of photoresponse amplitude saturation and to provide a good estimate of photoresponse velocity at higher intensities. A cascaded low-pass filter model with modifications to accommodate amplitude and timing nonlinearities was used to generate a set of probable underlying photoresponses from the analysis of a-wave amplitude and velocity. Movement of the a-wave leading edge to the left at higher intensities in algebraic combination with a static b-wave leading edge above the intensity of photoresponse amplitude saturation was found to explain the second rise of the b wave amplitude function and the decline of b-wave amplitude above baseline at high intensities. This analysis provides a basis for modeling the underlying photoresponse on a biochemical level and for interpreting photoreceptor damage in disease states. PMID- 1633746 TI - Light adaptation and the luminance-response function of the cone electroretinogram. AB - Cone electroretinograms are typically isolated by presenting stimulus flashes against rod-desensitizing adapting fields. To investigate the manner in which adapting-field luminance affects cone electroretinogram response properties, we measured cone electroretinogram luminance-response functions of two normal subjects, with stimuli presented against adapting fields that ranged in luminance from -1.2 to 2.1 log cd/m2. A flicker rate of 31.1 Hz was used to isolate cone electroretinograms under all adaptation conditions. A hyperbolic equation of the form (R/Rmax) = Ln/(Ln + Kn) was fitted to each luminance-response function by a least-squares criterion. As adapting field luminance increased, the best-fit values of the variables K and n increased, which is in general agreement with results of electrophysiologic studies of light adaptation in retinal neurons. However, Rmax values also increased with adapting field luminance. The change in all three of these variables with adapting field luminance must be considered in the interpretation of cone electroretinogram luminance-response functions from patients with retinal disorders. PMID- 1633747 TI - Use of 10-Hz flash visual evoked potentials in prediction of final visual acuity in diabetic eyes with vitreous hemorrhage. AB - In 44 diabetic eyes with vitreous hemorrhage, monocular steady-state visual evoked potentials were elicited through closed eyes by a 10-Hz flash. Visual evoked potentials were rated as normal or abnormal on the basis of amplitude and waveform. Abnormal visual evoked potentials were subdivided into mildly abnormal, markedly abnormal and nonrecordable categories. Patients with normal potentials were predicted to have visual acuities of 6/15 (20/50) or better. Patients with abnormal potentials were predicted to have visual acuities of 6/18 (20/60) or worse. Final visual acuities were the best visual acuities recorded in the 6 months after vitreous surgery (vitrectomy) or spontaneous clearing of the vitreous hemorrhage. The visual evoked potential categories and final acuities were compared with a 2 x 2 contingency table. The accuracy was 86%. The visual evoked potential categories and final acuities were associated at a statistically significant level. PMID- 1633748 TI - Visual evoked potential estimation of visual activity with a Laplacian derivation. AB - Visual acuity was estimated with visual evoked potentials in 13 healthy subjects. A Laplacian derivation of 5 electrodes was used to improve the signal-to-noise ratio and to enhance striate cortical activity selectively. In 6 subjects, the Laplacian derivation gave a more reliable estimation of visual acuity than did a single midline derivation. In the other 7 subjects, the quality of both estimations was comparable. PMID- 1633750 TI - Pathogenesis of alcoholic myopathy: roles of ethanol and malnutrition. PMID- 1633749 TI - The neural retina of the frog contributes a slow cornea-positive potential to the electroretinogram. AB - A c-wave-like cornea-positive potential in the isolated rabbit retina has been described. In this study, frog retinas were investigated to see if the neural retina contributes a slow cornea-positive component to the c-wave of the electroretinogram. The eye cups of both Rana esculenta and Rana temporaria exhibited a normal electroretinogram with c-wave, a larger proximal light-induced extracellular potassium increase, a small distal extracellular potassium increase and an extracellular potassium decrease around photoreceptors. Isolated frog retinas kept receptor side-upward in a moist chamber without perfusion showed the well-known slow PIII generated by the potassium decrease around receptors. If the isolated retinas were well perfused, the slow PIII was not seen, but a cornea positive d.c. potential sometimes appeared after the b-wave. The different slow potentials seemed to relate to different light-induced potassium changes in the proximal retina. There was a long-lasting proximal potassium increase in the superfused retinas but a quick return of the proximal potassium increase to the baseline in the retinas lacking oxygen at the vitreal side. The lasting proximal potassium increase in adequately maintained retinas may counteract the potassium decrease around receptors and cancel slow PIII. PMID- 1633751 TI - Experimental approaches to the evaluation of alcohol abuse and dependence development. AB - In rats, a complex longitudinal analysis of alcohol intake behaviour and electrophysiological sleep pattern was performed during different periods of stable voluntary alcohol consumption. By the sleep pattern, the existence of alcohol abuse and dependence development could be confirmed. Acute ethanol withdrawal was shown to be the obligatory and necessary element in alcohol abuse and dependence evaluation. The proposed behavioural and sleep pattern models might be used in the search for anti-alcoholic drugs in combination with the study of alcoholic aging processes. PMID- 1633752 TI - Craving: consensus of status and agenda for future research. AB - The term craving is used frequently in relationship to drug abuse and its treatment but there is disagreement over its definition and role. In February 1991, a meeting of experts from several disciplines, sponsored by the Addiction Research Center (ARC) of the National Institute on Drug Abuse, was convened with the goal of reaching consensus about the importance of craving and to suggest a future research program. The participants agreed that craving is a subjective state in humans that is associated with drug dependence but little is known about its determinants, relationship to drug taking, and measurement. To advance our knowledge, a substantial research program is required. The outcome of this research effort could have important consequences for increasing our understanding of the determinants of drug abuse. PMID- 1633753 TI - Triazolam as a discriminative stimulus in humans. AB - Seven healthy normal male and female volunteers (19-42 years) were trained to discriminate between the benzodiazepine triazolam (0.32 mg/70 kg; e.g. drug A) and placebo (e.g. drug B). During the first four daily sessions, drug A and drug B were administered orally in capsules 60 min prior to the session on alternate days and subjects were informed of the drug label at the time of drug administration. Subsequently, drug A and drug B were administered in a randomized block fashion and subjects identified the drug code they thought they received. Subjects were informed of the drug code post-session. Once the criterion for discrimination was met (i.e. correct drug code identification on four consecutive sessions), the dose-effect curve for triazolam (0.1-0.75 mg/70 kg) was determined. The discrimination was acquired in all subjects; triazolam (0.32 mg/70 kg) and placebo produced approximately 85-95% correct responding. During the dose-effect curve determination, triazolam produced dose-related increases in triazolam-appropriate responding and self-reported sedation and drug strength. These results indicate that a triazolam-placebo discrimination can be acquired and that the triazolam discriminative stimulus effect is related to dose and to self-reported sedation. PMID- 1633754 TI - The scientific/clinical response to the cocaine epidemic: a MEDLINE search of the literature. AB - Index Medicus (1966-1990) was searched to quantify and characterize the scientific/clinical community's responses to the cocaine epidemic. The rate of growth in the cocaine literature was compared with the rate of growth in the heroin and marijuana literatures in the 1960s and 1970s. Articles on cocaine increased dramatically over the past 7 years suggesting a clear response from the scientific/clinical community to the public health problems presented by the cocaine epidemic. That literature spans a wide range of areas addressing many scientific and health-care issues. This increase in cocaine citations is similar to that which occurred previously in response to use of heroin and marijuana. PMID- 1633755 TI - Alcohol abuse and dependence in an urban primary care clinic in Nigeria. AB - A two-stage epidemiological survey was conducted in an urban walk-in clinic in Nigeria to detect, among other disorders, the prevalence of alcohol abuse and dependence using DMS-IIIR criteria. At the first stage, respondents were administered the 12-item General Health Questionnaire and the Alcohol Use Disorders Identification Test (AUDIT). A proportion of the respondents were selected for detailed interview at the second stage using the Composite International Diagnostic Interview (CIDI). An estimated 1.7% of this sample met the criteria for alcohol abuse or dependence. All the identified cases were males, thus giving an estimated prevalence of 5.2% in males. In this setting, the AUDIT performed poorly as a screening instrument. It has a sensitivity of 32% but a specificity of 93%. Apart from reasons relating to the low base rates of the disorders under investigation, cultural factors influencing the ways alcohol use are perceived may explain this poor performance. PMID- 1633756 TI - Acupuncture fails to improve treatment outcome in alcoholics. AB - Fifty-six alcoholics (49 male, 7 female) of lower socioeconomic class attending an outpatient treatment program in Brooklyn, New York were prospectively randomized to one of three treatment group: point-specific acupuncture, sham transdermal stimulation or standard care (control). One third of the subjects reported a history of drug use in addition to alcohol. Results in this small sample showed no significant differences in attendance at Alcoholics Anonymous meetings, number of outpatients sessions attended, number of weeks in either the study or in the outpatient program, number of persons completing treatment or in the number of relapses. It is therefore concluded that in this small racially mixed sample of urban outpatient alcoholics, fixed point-specific standardized acupuncture did not improve outcome. We caution against the routine use of this treatment until more randomized controlled trials demonstrate a beneficial effect. PMID- 1633757 TI - Dexamethasone suppression test in alcohol withdrawal: relationship to depression and liver function. AB - The relationship between dexamethasone suppression test (DST) response, depressive symptoms and liver function tests was investigated in 15 male alcohol dependent patients for 2 weeks during alcohol withdrawal. Six of the patients relapsed into drinking within the investigation period. There was no association between DST response and relapse, which suggests that abnormal DST response has no predictive value for relapse into drinking. About 50% of the patients had abnormal DST responses during the first week of alcohol withdrawal. There was no relationship between DST response and depression or depressive symptoms. Depression remitted within 1-2 weeks, whereas DST responses remained abnormal for at least 2 weeks in 2 of the non-relapsing 9 patients. Abnormal DST response in alcohol withdrawal is unlikely to be due to alterations in liver function but may be attributable to the effect of alcohol on the hypothalamic-pituitary adrenocortical axis. PMID- 1633758 TI - Measuring the learning potential of abstinent alcoholics. AB - The performance of 89 Finnish alcoholics was measured on a Vygotskian test of learning potential. There were four questions to analyse: (1) can the performance of alcoholics be improved by means of instruction in non-verbal problem solving tasks; (2) how extensive is the transfer effect; (3) how does the duration of abstinence affect test performance; and (4) how does the actual performance level affect post-test results? Results indicated that instruction had a clear positive effect on the performance of alcoholics in simple tasks, but no transfer effect was evident in the more complex tasks. The duration of abstinence had no general effect. Although analysis of the mean scores of time-level groups showed some improvement in performance with increasing duration of abstinence, intra-group deviation was so high that the trends were not statistically significant. The subjects' actual performance level, on the other hand, was a very relevant factor. This was particularly evident in complex transfer tasks. PMID- 1633759 TI - Hip and knee joint replacements. PMID- 1633760 TI - [The long-term therapy of familial hypercholesterolemia with heparin-induced extracorporeal LDL precipitation]. AB - The long-term tolerance to and effectiveness of heparin-induced extracorporeal LDL precipitation (HELP) in combination with lipid reducing drugs and diet was tested in six patient (5 males, 1 female; mean age 48 +/- 4 years). Follow-up period was over 50 months, in one patient over 24 months, while one man had a sudden cardiac death 57 weeks after starting treatment. The study was divided into three phases. In phase I (24 months) treatment consisted of HELP and conventional lipid-reducing drugs; in phase II (12 months) of lovastatin (80 mg daily) and cholestyramine (12-24 g daily); and phase III (14 months) of HELP, lovastatin and cholestyramine. In phase I it was possible to lower the pre treatment level of LDL-cholesterol from 306 +/- 18 mg/dl to 173 +/- 13 mg/dl (43.5%). A similar effect (from 307 +/- 21 mg/dl to 155 +/- 17 mg/dl [-49.5%]) was obtained in phase II. The resumption of HELP reduced the pre-treatment LDL concentration to 136 +/- 9 mg/dl (-55.7%). The various treatment regimens were well tolerated. Biochemical data remained unchanged except for iron loss requiring substitution. Thus combined HELP, lovastatin and ion exchange offer for the first time an effective and reliable means in familial hypercholesterolaemia of clearly reducing long-term the mean LDL cholesterol level below the atherosclerosis threshold of 120 mg/dl. PMID- 1633761 TI - [The Shy-Drager syndrome]. AB - For 15 years a now 70-year-old woman had been having occasional episodes of circulatory collapse which 7 years ago were diagnosed as being caused by severe idiopathic orthostatic hypotension. These episodes had recently become much more frequent and she was hardly able to be upright for more than one minute. In the Schellong test the blood pressure fell from 80/50 mm Hg when lying to 70/30 mm Hg on standing, the pulse rate remaining unchanged at 60/min. The standing test had to be abandoned after 90 seconds. Serum catecholamine concentrations (epinephrine 65 ng/l, norepinephrine 100 ng/l) did not rise on standing (epinephrine 25 ng/l, norepinephrine 105 ng/l). 24-hour urinary excretion of vanillyl mandelic acid was at the lower limit of normal (2.2 mg). The autonomic dysfunction of circulatory control suggested a Shy-Drager syndrome. Other signs of autonomic failure included gastroparesis, decreased tear and sweat secretion and transitory urinary incontinence. Symptomatic treatment with elastic stockings, fludrocortisone, etilefrine, dihydroergotamine, L-dopa, yohimbine and amezinium methylsulfate gave the patient greater mobility without achieving normal blood pressure responses. PMID- 1633763 TI - [The plasma hyperviscosity syndrome as an oncological emergency]. PMID- 1633762 TI - [Severe digitalis poisoning after the ingestion of 1 g of digoxin]. AB - A 50-year-old, previously healthy, woman swallowed 1 g digoxin powder, dissolved in water, with suicidal intent. On admission to hospital one hour later, having vomited three times at home, the prominent signs were somnolence and hypersalivation. Serum digoxin level was 3.37 ng/ml. There followed repeated episodes of asystole alternating with ventricular fibrillation requiring cardiopulmonary resuscitation over 90 min and adrenaline administration. Repeated electrical defibrillation, administration of dopamine, phenytoin and lidocaine, as well as transitory transvenous electrical stimulation became necessary. Anti digoxin antibody fragments were administered, initially 80 mg, to a total of 3,280 mg over 24 hours. After 3 days of intensive care and a further 21 days in hospital she was discharged and referred to psychiatric treatment. This case demonstrates that even severe digoxin poisoning can be successfully treated without sequelae by the appropriate administration of digoxin antidote. The main problems in this case were regulation of the dosage and acquiring the necessary amount of antidote which greatly exceeded the hospital's own depot. PMID- 1633764 TI - [Autosomal-dominant polycystic kidney disease]. PMID- 1633765 TI - [Johann Friedrich Dieffenbach: 1792-1847. The "father of plastic surgery" in Germany]. PMID- 1633766 TI - [The draft of a law on technical assistants in medicine]. PMID- 1633768 TI - [Tumor necrosis factor and multiple sclerosis]. PMID- 1633767 TI - [The long-term action of caffeine]. PMID- 1633769 TI - Endoscopic ultrasonography in the diagnosis, staging and follow-up of esophageal and gastric cancer. AB - The accumulating data show that endoscopic ultrasonography (EUS) is highly compatible with the UICC/AJCC staging classification for esophageal and gastric cancer, based on the TNM system expressing anatomical extent of disease. The great strength of EUS in staging these cancers is its ability to image the gut wall and adjacent structures in unique detail. EUS is more accurate than computed tomography in staging the depth of primary tumor invasion (T) and regional lymph node metastases (N). High frequency EUS is not useful in staging for distant metastases (M) due to limited depth of the field. EUS also has limitations in reliably distinguishing between neoplastic and inflammatory tissue. Thus, the major use of EUS is in staging rather than in diagnosis. However, initial reports indicate that EUS may be helpful in the detection of malignancy in Barrett's esophagus, in diagnosing post-operative recurrent cancer, and in evaluating the response to non-operative therapy. EUS appears to represent an important advance in the staging and follow-up of patients with esophageal and gastric cancer. Instruments and techniques will continue to evolve, but the next level of research should be designed to show that the improved staging provided by EUS has clinical utility and can affect patient outcome. PMID- 1633770 TI - Endoscopic ultrasonography in diagnosis and staging of pancreatic and biliary tumors. PMID- 1633771 TI - Endosonography of colorectal diseases. PMID- 1633772 TI - Endosonographic diagnosis of metastatic lymph nodes in gastric carcinoma. PMID- 1633773 TI - Enlarged lymph nodes: malignant or not? AB - Prospective controlled data of lymph node evaluation by endoscopic ultrasound in esophageal, gastric and pancreatic cancer is presented. Lymph node pattern, changes of boundaries and echogenicity were considered. Preoperative findings of endoscopic ultrasound were classified according to TNM staging. Only those cases with subsequent histologic examination of the resected specimen were entered into the study. Sensitivity of endoscopic ultrasonography (EUS) was 90% for esophageal and 87% for gastric cancer. The specificity was 72% and 88%, respectively. In spite of the overall satisfactory results of EUS in evaluation of lymph nodes, further improvement in detection and differentiation of benign and malignant nodes is required. PMID- 1633774 TI - Endosonography-guided treatment of esophageal carcinoma. AB - Endosonography is helpful in managing patients with esophageal cancer due to its capacity to stage the tumor for the depth of tumoral invasion and the presence of metastatic lymph nodes. Thus, ES will help the surgeon to determine if surgery is advisable. If the patient does not undergo surgery, it will provide a very accurate prognosis and allow the adaptation of non-surgical multimodal therapy to determine tumor extension. Finally, following the initial phase of treatment. ES will be useful in the follow-up, especially to detect and stage recurrences. PMID- 1633775 TI - Application of ultrasonic probes prior to endoscopic resection of early gastric cancer. AB - The development of a new strip biopsy technique for endoscopic mucosectomy utilizing endoscopic saline injection and a double-channel endoscope permits the safe and simple resection of superficial type early gastric cancer which has been difficult to perform with conventional polypectomy techniques. Preresection assessment of the depth of invasion and postresection assessment of efficacy are important with regard to treatment of early gastric cancer, but conventional endoscopic ultrasonography employed for this purpose requires special equipment and involves intricate procedures. An ultrasonic probe which can be used endoscopically has recently been developed and is currently in the trial stage. The authors have conducted studies with respect to a 7.5 MHz radial scanning type Miniature Ultrasonic Probe as well as a 20 MHz manual linear scanning type Sonoprobe System. Experimental studies indicated that the former type is capable of delineating postresection ulcers, while the latter permitted delineation of tumors as hypoechoic images in 9 of 11 cases of early gastric cancer. PMID- 1633776 TI - EUS-guided therapy in rectal tumors and other fields of minimal invasive surgery. PMID- 1633777 TI - The role of endoscopic ultrasonography in esophageal motility disorders. PMID- 1633778 TI - Value of endoscopic ultrasonography in the management of portal hypertension. AB - Using endoscopic ultrasonography (EUS) a large part of the portal venous system can be visualized. In 40 patients with portal hypertension (PH) and in 48 control subjects EUS displayed the azygos, splenic, mesenteric and portal veins in both groups. However, esophageal and gastric varices, peri- esophageal and peri gastric collateral veins and submucosal gastric venules were displayed only in patients with PH. EUS was inferior to endoscopy for detecting and grading esophageal varices (p less than 0.0005), but superior in the detection of varices in the fundus of the stomach (p less than 0.0005). EUS cannot be considered a reliable method for the study of esophageal varices: it has an overall sensitivity of 50%, does not permit flow measurements, and does not provide information that could be used to estimate the risk of bleeding. EUS has been demonstrated to be superior to endoscopy in the diagnosis of gastric varices. This finding is extremely important for the optimal selection of treatment of patients with portal hypertension. EUS can detect portal hypertensive gastropathy; thus inflammatory gastritis can be more easily distinguished from congestive gastropathy and therapeutic decisions are strongly influenced. PMID- 1633779 TI - Endoscopic ultrasonography in the diagnosis of chronic pancreatitis. AB - Endoscopic ultrasonography (EUS) is highly accurate in the diagnosis of chronic pancreatitis. Both parenchymal and ductal changes indicative of chronic pancreatitis can be identified. Parenchymal changes include small cystic abnormalities and hyperechoic foci scattered throughout the gland; the entire gland may be enlarged in early chronic pancreatitis, or small and atrophic in advanced disease. Ductal changes include enlargement of the main pancreatic duct or secondary branches, and the presence of stones or proteinaceous plugs within the ducts. Pseudocysts appear as cystic structures of mixed echogenicity; EUS is able to detect small pseudocysts or masses not identified by conventional imaging modalities. EUS has some difficulty in distinguishing benign from malignant pancreatic masses, particularly when the lesions are small. EUS should not supplant the use of CT scan or ERCP in the differential diagnosis of pancreatic disease, but is rather an adjunct to these studies. Future clinical research should focus on determining the appropriate indications for EUS in pancreatic disease, and determining if patient outcomes are favorably affected by the diagnostic information obtained. PMID- 1633780 TI - Value of endoscopic ultrasonography in the assessment of inflammatory bowel diseases. AB - The value of EUS in the assessment of inflammatory bowel diseases was determined. EUS was useful for estimation of the histological changes of inflammatory bowel diseases. In ulcerative colitis, EUS findings were classified into five types, which correlated with the colonoscopic and histological findings. Studies in surgical cases and further prospective investigations are necessary, however, to determine whether EUS can contribute to the management of inflammatory bowel diseases. PMID- 1633781 TI - Endosonographic differentiation of mucosal and transmural nonspecific inflammatory bowel disease. AB - Thirty-seven patients with nonspecific inflammatory bowel disease were examined with an ultrasonic colonoscope and the inflammation classified as mucosal or transmural. Mucosal inflammation was characterized by preservation of the five layer structure of the wall with thickening of the submucosa. Transmural inflammation was endosonographically defined as sectional interruption or loss of the five-layer structure. In 14 of the 37 patients a colectomy was performed. Examination of 3 of the 14 resected specimens revealed inflammation confined to the mucosa. This was consistent in all three cases with the preoperative endosonographic evaluation. Eleven of the 14 resected specimens showed sectional transmural inflammation. Ultrasonographically all of the 11 patients fulfilled the criteria for transmural inflammation, whereas endoscopic and microscopic signs were consistent with transmural inflammation in 9 of the 11. Endosonography of the colon enables definition of mucosal inflammation thus providing criteria for selection of patient for ileoanal pouch construction. PMID- 1633782 TI - Clinical application of linear ultrasound probes. AB - The linear ultrasound probe should be viewed as an adjunct to conventional endoscopic ultrasonography with combined ultrasound endoscopes. It certainly does not replace these instruments for staging neoplasms and imaging extraintestinal organs such as the pancreas. It can be a simpler alternative to these instruments when applied at the time of endoscopy to obtain more information about wall thickness and the cause of an intramural mass. It can add information when used to image within impassable malignant strictures. Further development of the linear probes with the addition of a balloon over the transducer and the advent of new probes that utilize other scanning mechanisms is anticipated and should make this imaging system even more useful. PMID- 1633783 TI - Clinical application of ultrasonic probes in the biliary and pancreatic duct. AB - The clinical use of an ultrasonic probe with the radial scan transducer in the biliopancreatic ducts is reported in 35 patients with biliopancreatic lesions, including 11 cases of bile duct and 5 of pancreatic carcinoma. Two approaches are available for the intraductal scanning of bile and/or pancreatic ducts. One is the percutaneous insertion via a percutaneous transhepatic biliary fistula established for cholangioscopy. The other approach is the transpapillary insertion of the probe via the working channel of the duodenoscope. Using both approaches, ultrasonographic images of the bile duct wall, pancreas head and neighboring major blood vessels could be observed clearly. The extent of bile duct and pancreatic carcinoma could also be visualized. We believe that intraductal scanning using ultrasonic probes is a promising method in the staging of biliopancreatic malignancy. PMID- 1633784 TI - Intravascular ultrasonography in tumor staging. PMID- 1633785 TI - Manual materials handling I: general research issues. A special issue in honour of Professor M. M. Ayoub. PMID- 1633786 TI - Discriminability of load heaviness: implications for the psychophysical approach to manual lifting. AB - The main objective of this study was to investigate human ability to discriminate between different levels of load heaviness in manual lifting. Twelve male college students participated in the laboratory experiment. Twenty-eight sequences of five boxes that weighed from 5 to 64 lbs (2.27-29.1 kg) were used. The subjects were asked to arrange boxes in each sequence in order of the perceived (increasing or decreasing) heaviness, i.e., from lightest to the heaviest box, or from heaviest to the lightest box. The subjects were also asked to assign linguistic descriptors of perceived load heaviness to each box in the sequence, and to indicate the confidence levels regarding correctness of the assigned box order and assignment of linguistic values. The independent variables included magnitude of weight and load differential between the successive weights in a sequence. The number of sequential ordering errors, assignment of linguistic variables, and estimated confidence levels were highly dependent on the load differential and weight range. It was concluded that in order to assure reliable results of the psychophysical approach to determining the values of maximum acceptable weight of lift, the adjustment process for male subjects should require using small weights of at least 4 lbs (1.8 kg) to be added or removed from the lifted box. The results of this study also suggest that the error rate in load discriminability can be controlled below the 10% level, if the relative difference in weight between successive boxes lifted is at least 12%. Given the above findings, it is suggested that usefulness of some of the recommendations for setting safe limits for manual lifting tasks, which were reached based on the psychophysical approach and broadly reported in the past, may need to be carefully re-examined. Finally, this study showed that the Weber fraction for load heaviness over the range of lifted weights from 8.6 to 29.1 kg is between 0.03 and 0.04. PMID- 1633787 TI - Psychophysical capacity of industrial workers for lifting symmetrical and asymmetrical loads symmetrically and asymmetrically for 8 h work shifts. AB - This paper presents comprehensive maximum acceptable weight of lift (psychophysical lifting capacity) database for male and female industrial workers for lifting symmetrical and asymmetrical loads symmetrically and asymmetrically for 8 h work shifts. The experimental data collected in previous studies on experienced (industrial) and inexperienced (non-industrial) materials handlers (Mital 1984a, Mital and Fard 1986) and the patterns of responses between the two populations (Mital 1985, 1987) were used to generate this database. Since previous work (Mital 1985, 1987) showed that responses of both experienced and inexperienced materials handlers to task variables are similar and also provided multipliers relating the psychophysical lifting capacities of the two populations, it was possible: (1) to convert psychophysical capacity data for asymmetrical lifting of symmetrical and asymmetrical loads, collected on inexperienced workers to reflect psychophysical lifting capacity of experienced workers for asymmetrical lifting; and (2) to take psychophysical lifting capacity data of experienced industrial workers for symmetrical lifting of symmetrical loads and generate from it their psychophysical lifting capacity for symmetrical and asymmetrical lifting of symmetrical and asymmetrical loads by using the response patterns of inexperienced workers to lifting symmetrical and asymmetrical loads symmetrically and asymmetrically. Both approaches were used and, as expected, provided almost identical values for the psychophysical lifting capacity of industrial workers for symmetrical and asymmetrical lifting of symmetrical and asymmetrical loads. Therefore, the final database tables provided in this paper used combined values generated by the two methods. PMID- 1633789 TI - The load on the lumbar spine during asymmetrical bi-manual materials handling. AB - Previous biomechanical analyses of typical load manipulation tasks were mainly limited to sagittal-plane activities or to static cases. This paper includes the biomechanical determination and assessment of lumbar load during asymmetrical bi manual materials handling tasks which involve lateral turning of the body, trunk inclination, and sagittal flexion and lateral bending of the spine. Diagonal lifting tasks were analysed for different values for load weight (0-40 kg) and task duration (0.75-1.5 s). Whereas a constant grasp height of 15 cm was assumed, the height for releasing the load differed (50, 100, 150 cm). A dynamic spatial human model ('The Dortmunder') was used for calculating the torque in the sagittal, frontal, and transversal planes through the lumbosacral joint and for determining the compressive and the sagittal and lateral shear force at the L5-S1 disc. The trajectories of body segments and load are computer-simulated on the basis of postures adopted during the movement. During diagonal lifting of loads, lumbosacral torque in the sagittal plane is considerably larger than the lateral bending and torsional torque components. Dynamic analyses result in higher maximum values in the lumbar-load time curves than static analyses. The shorter the time for task execution, the higher the resultant dynamic effects and, in consequence, the higher the lumbar load. Lumbosacral compression and shear increase with increasing load-release heights due to higher acceleration and retardation of body and load when the same grasp position and task duration are assumed. The maximum load-bearing capacity of the lumbar spine was determined on the basis of strength data for isolated lumbar segments provided in the literature. The compressive strength falls within the same range as the compressive forces calculated for asymmetrical lifting of loads up to 40 kg. On account of the wide scattering of the compressive strength values, the main influences were determined (age and gender). At an age of 40 years, strength is approx. 6.7 kN for males and 4.7 kN for females (decrease with age per decade: 1.0 kN males, 0.6 kN females). In order to avoid overestimating an individual's lumbar compressive strength, predicted values should be reduced, e.g., by the standard deviation in the male or female samples (2.6 kN or 1.5 kN). Although only a few maximum shear force values are available in the literature, comparison with the calculated values for diagonal lifting leads to the conclusion that sagittal and lateral shear should not be ignored in the assessment of lumbar load during asymmetrical handling tasks. PMID- 1633788 TI - Margin of safety for the human back: a probable consensus based on published studies. AB - Despite numerous efforts to control occurrences of work-related low back pain, it continues to be a significant problem. Since the causation of low back pain is under multifactorial control, it is suggested that the factor most vulnerable at any given time will determine the safety. Epidemiological, biomechanical, physiological, and psychophysical information presented in published literature has been analysed. The data available are related to injuries and the projected margin of safety. This paper therefore, is an integrative, inferential synthesis of the published work to discern the margin of safety. An attempt has been made to conclude, on the basis of objective evidence, an all encompassing criterion to ensure the safety of the back. The psychophysical approach appears to integrate biomechanical and physiological variables on a short term basis in the studies surveyed. However, it remains to be proven that the sensory conditioning due to prolonged and repetitive occupational tasks will remain responsive to cumulative load and fatigue failures. PMID- 1633790 TI - Manual materials handling capabilities in non-standard postures. AB - Research efforts to establish manual materials handling (MMH) capabilities of individuals and populations have been conducted for many years. Most of the previous efforts have explored 'standard postures', utilizing two-handed, symmetric, sagittal plane MMH using unrestricted postures. Recognizing that many industrial MMH activities do not utilize 'standard postures', recent research projects have explored psychophysically determined MMH capacities in a variety of non-standard postures. Among the non-standard postures examined were: twisting while lifting or lowering, lifting and lowering from lying, sitting, kneeling, and squatting positions, and carrying loads under conditions of constricted ceiling heights. This paper presents the results of a series of previous research efforts at Texas Tech University. The results are presented in the form of population capabilities of both males and females for 99 MMH tasks using 'non standard postures'. The data tables contain means and standard deviations of the data, as well as percentile distributions for the subject populations. Sample sizes for the experimental populations ranged from 45 to 50 subjects of each sex in the first three experiments to 20 subjects of each sex in the fourth set of experiments. PMID- 1633791 TI - The effects of speed, frequency, and load on measured hand forces for a floor to knuckle lifting task. AB - The purpose of this study was to describe and quantify measured hand forces during floor to knuckle lifting of various loads. Hand forces of five subjects were measured with a strain gauge apparatus for normal and fast speeds of lifting at 1, 4, and 8 l/min. The pattern of hand force over time exhibited peaks in force in the shape of a spike for all fast lifts, indicating that subjects did not lift smoothly. For normal speed of lift, only one of the five subjects executed some lifts smoothly, indicating that it may be possible to lift smoothly, but most lifters probably do not. Peaks of horizontal and vertical components of hand force were tabulated by speed of lift, frequency, and load. PMID- 1633792 TI - Quantification of back motion during asymmetric lifting. AB - The objective of this study was to determine how trunk motion characteristics (in all three planes of the trunk) change as a free dynamic lifting task becomes more asymmetric. Trunk motion characteristics included range of motion, velocity (peak and average), and acceleration. Previous studies have shown that trunk motion characteristics affect trunk strength as well as the action of the trunk musculature. These trunk motion characteristics were quantified as a function of seven task asymmetries and three task weights. The experimental task required the subject to lift materials in positions commonly seen in the workplace. The range of motion, peak velocity, average velocity, and peak acceleration in each plane of the body were documented during the tasks. Generally, trunk motion characteristics in all three planes increased with an increase in task asymmetry. However, with an increase in task weight all the sagittal plane parameters and one transverse plane parameter decreased. Models were constructed to predict trunk motion characteristics given a task asymmetry and weight. When these motion components were compared to dynamic strength estimates from previous studies it was found that dynamic asymmetric lifts could reduce available strength up to 21% of maximum static strength. The results provide new insight into factors associated with the risk of developing low back disorders. PMID- 1633793 TI - Static and dynamic lifting strength at different reach distances in symmetrical and asymmetrical planes. AB - Postural and therefore biomechanical standardization in strength testing has not been rigorously and consistently applied. To develop a quantitative relationship between strength and posture (body position, symmetry, and reach) 30 normal subjects (18 male and 12 females) were required to stoop and squat lift or exert in the relevant posture against a standardized instrumented handle. The isometric lifting efforts and isokinetic lifts were studied. The isokinetic lifts were done at a linear velocity of 50cm/s of the hand displacement from the floor to the knuckle heights of the respective subjects in stoop and squat postures. The isometric stoop lifting efforts were exerted in two standardized postures: (a) with 60 degrees hip flexion; and (b) with 90 degrees hip flexion. The isometric squat lifting efforts were also exerted in two standardized postures: (a) with 90 degrees knee flexion; and (b) with 135 degrees knee flexion. All isometric lifting efforts and isokinetic lifts were performed at half, three-quarters, and full horizontal reach in sagitally symmetrical, 30 degrees left lateral, and 60 degrees left lateral planes. Isometric stoop and squat lifting efforts were also measured in self-selected optimal postures. These 56 conditions were tested in random order. The analysis of variance revealed that the gender, the mode of lifting, the postural asymmetry and reach of lifting affected the strength significantly (p less than 0.0001). Most two-way and three-way interactions were significant (p less than 0.01). Of 108 prediction regression equations, 103 were significant with up to 90% of the variation explained by anthropometric variables and sagittal plane strength. The reach affected the strength most profoundly followed by postural asymmetry and the mode of lifting. PMID- 1633794 TI - Biomechanically and electromyographically assessed load on the spine in self paced and force-paced lifting work. AB - The purpose of this study was to measure dose of spinal load when different pacing methods were applied to lifting work and to develop methodology for such measurements. The compressive load on the spine computed by a dynamic biomechanical model and the electromyographic activity of back muscles were used for describing the spinal load. Five men and five women worked in a laboratory on two days lifting a box up and down for 30 min on both days, on one day force paced (4 lifts/min), and on the other self-paced in random order. The weight of the box was rated by the subjects to be acceptable for the work done. The lift rate of our female subjects was higher and that of the male subjects lower in self-paced than in force-paced work. There were no significant differences in peak lumbosacral compressions nor in the amplitude distributions of electromyography between the two pacing methods. The biomechanically-calculated compressive forces on the spine were lower (about 2.7 kN for the men and 2.3 kN for women) than the biomechanical recommendations for safe lifting, but the EMG activity showed quite high peaks so that for 1% of work time the activity was on women above 60% and on men above 40% of the activity during maximum isometric voluntary test contraction. PMID- 1633795 TI - An electromyographic analysis of seated and standing lifting tasks. AB - The objective of this project was to compare the muscular effort exerted during manual lifting tasks performed in standing versus seated posture. Six male undergraduate and graduate students performed 12 different static and dynamic lifts in both sitting and standing positions. During each effort electromyographic (EMG) data were collected on four muscles groups (low back, upper back, shoulder, and abdominals). Four contractions were designed to elicit maximum muscular effort in the four groups being monitored. The remaining data were then expressed as a percentage of maximum EMG. Each subject performed the following: maximum static lift when sitting; maximum static lift when standing; sitting, static lift with 15.9 kg; standing, static lift with 15.9 kg; dynamic sit-forward lift with 15.9 kg, dynamic stand-forward lift with 15.9 kg, dynamic sit-twist with 15.9 kg, dynamic stand-vertical lift with 15.9 kg. Each of the lifts was performed with a wooden tray with slotted handles. Root mean square (RMS) values of the EMG data were calculated for three second periods. EMG activity in the low back, upper back, and shoulder was greater during sitting lifting than during standing lifting. The sit-twist lift resulted in the highest EMG in the abdominal muscles. Dynamic lifts resulted in more muscle activity than did static lifts. From these data it was concluded that sitting-lifting results in greater stress in the low back, upper back, and shoulders than does lifting while standing. PMID- 1633796 TI - An exponential model of isometric muscular fatigue as a function of age and muscle groups. AB - Despite the recommendations that an important design criterion is not to exceed 15% of an operator's maximum voluntary contraction (MVC) with any muscle that must be used for a long period of time, many tasks involve the exertion of much higher forces coupled with long-term contractions. Many studies have investigated the force-time relationship of isometric muscle contractions to determine the endurance time of a given relative force. To date, however, direct studies of muscle performance throughout fatiguing tasks have not been conducted to the same degree. This research was concerned with studying the effects of different muscle groups (biceps vs quadriceps) of subjects with different age groups (20-29 vs 50 59 years of age) on long-term muscular isometric contractions at different levels of %MVC (20%, 40%, 60%, 80%, and 100% MVC), and modelling the functional data to describe the time course of strength decrement. The data revealed that the time course of strength decrement was best modelled by the function: [formula: see text] An experiment, using 20 subjects with each subject performing 10 conditions (two muscle groups x five levels of %MVC), showed that this function accounted for over 95% of the variance of strength decrement. All parameter estimates were statistically significant. PMID- 1633797 TI - Bibliography. PMID- 1633798 TI - Nervous control of liver metabolism and hemodynamics. PMID- 1633799 TI - Molecular cloning of a glucoamylase gene from a thermophilic Clostridium and kinetics of the cloned enzyme. AB - Clostridium sp. G0005 produces a cell-bound glucoamylase (CGA). The gene encoding CGA has been sequenced. The deduced amino acid sequence begins with a putative 21 residue signal sequence for secretion of bacterial lipoproteins, which suggests that a putative CGA precursor is modified and secreted like other bacterial lipoproteins in Clostridium sp. G0005, and that the modified residue is important in the cell-bound form of mature CGA. Comparison of the amino acid sequence of the CGA precursor with known eukaryotic enzymes showed several regions of high similarity in spite of low similarity throughout the overall primary structure. CGA is the first bacterial glucoamylase to be cloned. The CGA gene was expressed in Escherichia coli cells with an inducible expression plasmid, in which the 5' non-coding region and the N-terminal coding region of the gene were replaced with the lac promoter. Kinetic studies of the cloned enzyme purified from E. coli were performed with a set of linear malto-oligosaccharides as substrates, and the subsite affinity was calculated from the kinetic parameters. CGA had typical kinetic properties for a glucoamylase, but this bacterial enzyme had higher isomaltose-hydrolyzing activity than other eukaryotic glucoamylases. PMID- 1633800 TI - Identification of cholecystokinin/gastrin peptides in frog and turtle. Evidence that cholecystokinin is phylogenetically older than gastrin. AB - Peptides homologous to mammalian cholecystokinin (CCK) and gastrin in brain, antrum, and small intestine of an amphibian (the bullfrog, Rana catesbeiana) and a reptile (the turtle, Pseudomys scripta) were characterized. All tissues contained peptides reacting with antisera specific for the carboxyamidated C terminal tetrapeptide common for CCK and gastrin. Extracts of all tissues, except the turtle antrum, also reacted with an antiserum specific for mammalian sulfated CCK, while no extract contained peptides reacting with an antiserum specific for mammalian gastrin. Both species contained predominantly small acidic forms in the brain and larger less acidic forms in the antrum and intestine. The antral peptides of both species were identified. The largest frog gastrin was a 47 residue peptide: DLLASLTHEQ KQLIMSQLLP ELLSELSNAE DHLHPMRDRD YAGWMDF.NH2. The largest turtle gastrin was a 52-residue peptide: DLLEALSQDQ KLLMAKFLPH IYAELANREG NWHEDAALRP LHDHDYPGWM DF.NH2. They display 51% similarity. Having Tyr in position 7 from the C-terminus, both resemble structurally mammalian CCK rather than gastrin, which suggests that CCK is phylogenetically older than gastrin. The turtle antral peptide contains a Tyr followed by Pro as in chicken gastrin. Thus, apparently at the stage of reptiles, a route different from the mammalian was taken in order to evolve a specific gastrin function. PMID- 1633801 TI - A correlation-coefficient method to predicting protein-structural classes from amino acid compositions. AB - A protein is usually classified into one of the following four structural classes: all alpha, all beta, (alpha + beta) and alpha/beta. In this paper, based on the maximum correlation-coefficient principle, a new formulation is proposed for predicting the structural class of a protein according to its amino acid composition. Calculations have been made for a development set of proteins from which the amino acid compositions for the standard structural classes were derived, and an independent set of proteins which are outside the development set. The former can test the self consistency of a method and the latter can test its extrapolating effectiveness. In both cases, the results showed that the new method gave a considerably higher rate of correct prediction than any of the previous methods, implying that a significant improvement has been achieved by implementing the maximum-correlation-coefficient principle in the new method. PMID- 1633802 TI - Inhibition of triosephosphate isomerase from Trypanosoma brucei with cyclic hexapeptides. AB - Two series of oligopeptides have been synthesized. Their effects on the activity of purified triosephosphate isomerase from Trypanosoma brucei and various other organisms have been studied. Using detailed three-dimensional structure information, the first series consisted of both cyclic and linear hydrophilic peptides that were designed to mimic the beta turns of the subunit interface loops of the trypanosome triosephosphate isomerase dimer. None of these exerted any inhibitory effect. The second series consisted of more hydrophobic cyclic peptides, originally designed to inhibit a hepatic transport system. Several of these were very effective in inhibiting the trypanosome triosephosphate isomerase, but not the homologous enzymes from rabbit, dog, yeast or Escherichia coli. The most active peptide, cyclo[-Trp-Phe-D-Pro-Phe-Phe-Lys(Z)-], exerted 50% inhibitory activity at a concentration of 3 microM. The nature of the inhibitory action of one of these compounds cyclo[-Trp-Tyr(OSO3Na)-D-Pro-Phe-Thr(OSO3Na) Lys(Z)-] was studied in more detail. Its inhibition was noncompetitive and reversible and more than one peptide was able to bind/active site. PMID- 1633803 TI - Identification and purification of the ornithine/citrulline carrier from rat liver mitochondria. AB - The ornithine/citrulline carrier from rat liver mitochondria, solubilized with Triton X-100 and partially purified on hydroxyapatite, was identified and completely purified by PD-10, DEAE-Sephacel and celite chromatography. On SDS/polyacrylamide gel electrophoresis, the purified ornithine/citrulline carrier consisted of a single protein band with an apparent molecular mass of 33.5 kDa. When reconstituted into liposomes the ornithine carrier protein catalyzed an active mersalyl sensitive ornithine/ornithine exchange. It was purified 438-fold with a recovery of 38% and a protein yield of 0.09% with respect to the extract derived from mitoplasts. The purified and reconstituted protein did not catalyze a significant unidirectional transport of ornithine. Citrulline was found to be the best countersubstrate for the transport of ornithine, followed by lysine and arginine. The exchange activity was inhibited by several sulphydryl reagents. PMID- 1633804 TI - Lipoamide dehydrogenase from Azotobacter vinelandii: site-directed mutagenesis of the His450-Glu455 diad. Kinetics of wild-type and mutated enzymes. AB - Three amino acid residues in the active site of lipoamide dehydrogenase from Azotobacter vinelandii were replaced with other residues. His450, the active-site base, was replaced with Ser, Tyr or Phe. Pro451, from X-ray analysis found to be in cis conformation positioning the backbone carbonyl of His450 close to N3 of the flavin, was changed to Ala. Glu455, from X-ray analysis expected to be involved in modulating the pKa of the base (His450), was replaced with Asp and Gln. The general conclusion is that mutation of the His-Glu diad impairs intramolecular electron transfer between the disulfide/dithiol and the FADH-/FAD. The wild-type enzyme functions according to a ping-pong mechanism in the physiological reaction in which the formation of NADH is rate-limiting. Above pH 8.0 the enzyme is strongly inhibited by the product NADH. The pH dependence of the steady-state kinetics using the NAD+ analog 3-acetylpyridine adenine dinucleotide (AcPyAde+) reveals a pKa of 8.1 in the pKm AcPyAde+ plot indicating that this pKa is related to the deprotonation of His450 [Benen, J., Berkel van, W., Zak, Z., Visser, T., Veeger, C. & Kok de, A. (1991) Eur. J. Biochem. 202, 863 872] and to the inhibition by NADH. The mutations considerably affect turnover. Enzymes with the mutations Pro451----Ala, His450----Phe and His450----Tyr appear to be almost inactive in both directions. Enzyme His450----Ser is minimally active, V at the pH optimum being 0.5% of wild-type activity in the physiological reaction. Rapid reaction kinetics show that for the His450-mutated enzymes the reductive half reaction using reduced 6,8-thioctic acid amide [Lip(SH)2] is rate limiting and extremely slow when compared using reduced 6,8-thioctic acid amide [Lip(SH)2] is rate-limiting and extremely slow when compared to the wild-type enzyme. For enzyme Pro451----Ala it is concluded that the loss of activity is due to over-reduction by Lip(SH)2 and NADH. The Glu455-mutated enzymes are catalytically competent but show strong inhibition by the product NADH (enzyme Glu455----Asp more than Glu455----Gln). The inhibition can largely be overcome by using AcPyAde+ instead of NAD+ in the physiological reaction. The rapid reaction kinetics obtained for enzymes Glu455----Asp and Glu455----Gln deviate from the wild-type enzyme. It is concluded that this difference is due to cooperativity between the active sites in this dimeric enzyme.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1633805 TI - Lipoamide dehydrogenase from Azotobacter vinelandii. The role of the C-terminus in catalysis and dimer stabilization. AB - The 10 C-terminal residues are not visible in the crystal structure of lipoamide dehydrogenase from Azotobacter vinelandii, but can be observed in the crystal structures of the lipoamide dehydrogenases from Pseudomonas putida and Pseudomonas fluorescens. In these structures, the C-terminus folds back towards the active site and is involved in interactions with the other subunit. The function of the C-terminus of lipoamide dehydrogenase from A. vinelandii was studied by deletion of 5, 9 and 14 residues, respectively. Deletion of the last 5 residues does not influence the catalytic properties and conformational stability (thermoinactivation and unfolding by guanidinium hydrochloride). Removal of 9 residues results in an enzyme (enzyme delta 9) showing decreased conformational stability and high sensitivity toward inhibition by NADH. These features are even more pronounced after deletion of 14 residues (enzyme delta 14). In addition Tyr16, conserved in all lipoamide dehydrogenases sequenced thus far, and shown from the other structures to be likely to be involved in subunit interaction, was replaced by Phe and Ser. Mutation of Tyr16 also results in a strongly increased sensitivity toward inhibition by NADH. The conformational stability of both Tyr16 mutated enzymes is comparable to enzyme delta 9. The results strongly indicate that a hydrogen bridge between tyrosine of one subunit (Tyr16 in the A. vinelandii sequence) and histidine of the other subunit (His470 in the A. vinelandii sequence), exists in the A. vinelandii enzyme. In the delta 9 and delta 14 enzymes this interaction is abolished. It is concluded that this interaction mediates the redox properties of the FAD via the conformation of the C-terminus containing residues 450-470. PMID- 1633806 TI - Characterisation of a haem active-site mutant of horseradish peroxidase, Phe41--- Val, with altered reactivity towards hydrogen peroxide and reducing substrates. AB - A horseradish peroxidase variant ([F41V] HRP-C*), in which Val replaces the conserved Phe at position 41 adjacent to the distal His, has been constructed. Its composition and spectroscopic, catalytic and substrate-binding properties were compared with those of the wild-type recombinant (HRP-C*) and plant (HRP-C) enzymes. Presteady-state kinetic measurements of the rate constant for compound I formation (k1) revealed an eightfold decrease in the reactivity of the Phe41--- Val variant towards H2O2, in comparison with HRP-C or HRP-C*. Measurement of the remaining rate constants, k2 and k3, for the two single-electron reduction reactions of [F41V] HRP-C with para-aminobenzoic acid as reducing substrate, showed that they were 2.5-fold and 1.3-fold faster, respectively. In contrast, analysis of data from steady-state assays with 2,2'-azinobis(3 ethylbenzthiazoline-6-sulphonate) as reducing substrate, showed decreased reactivity of the mutant enzyme to this compound, indicating a change in substrate specificity. Over the substrate range studied, the data for HRP-C* and for [F41V] HRP-C conformed to a simple modification of the accepted peroxidase mechanism in which a first-order step (ku), assumed to be product dissociation, becomes rate-limiting under our standard assay conditions. Calculations of rate constants from steady-state data yielded values of k1 for both enzyme forms in adequate agreement with those from pre-steady state measurements. They showed, furthermore, that both k3 for 2,2'-azinobis(3-ethylbenzthiazoline-6-sulphonate) and ku were substantially decreased, fivefold and tenfold, respectively, in the mutant. Analogous to the decrease in ku, we observed a twofold increase in the affinity of the mutant variant for the inhibitor benzhydroxamic acid. The coordination-state equilibrium of the haem iron also appeared shifted towards the hexacoordinate high-spin form. These observations indicate that in addition to affecting reactivity to H2O2, mutations in the distal region and close to the haem iron also affect reactivity towards different reducing substrates, inducing perturbations in the neighbourhood of the aromatic-substrate-binding site, known to be 0.8-1.2 nm from the haem iron. PMID- 1633807 TI - Structural studies by proton-NMR spectroscopy of plant horseradish peroxidase C, the wild-type recombinant protein from Escherichia coli and two protein variants, Phe41----Val and Arg38----Lys. AB - Wild-type recombinant horseradish peroxidase isoenzyme C and two protein variants, Phe41----Val and Arg38----Lys, have been characterised using both one- and two-dimensional NMR spectroscopy. Proton NMR spectra recorded in both resting and cyanide-ligated states of the proteins were compared with those of the corresponding plant peroxidase. The latter contains 18% carbohydrate in eight N linked oligosaccharide side chains whereas the recombinant proteins are expressed in nonglycosylated form. The spectra of the plant enzyme and refolded recombinant protein are essentially identical with the exception of carbohydrate-linked resonances in the former, indicating that their solution structures are highly similar. This comparison also identifies classes of carbohydrate resonances in the plant enzyme which provides new information on the local environment and mobility of the oligosaccharide side chains. Comparison of the spectra of the cyanide-ligated states of the two variants and those of plant horseradish peroxidase C indicated that there were significant differences with respect to haem and haem-linked resonances. These could not be rationalised simply on the basis of the local perturbation expected from a single-site substitution. The two substitutions made to residues on the distal side of the haem apparently influenced the degree of imidazolate character of the proximal His170 imidazole ring thus perturbing the magnetic environment of the haem group. Inspection of the spectra of the Phe41----Val variant also showed that the resonances of a phenylalanine residue in the haem pocket had been incorrectly assigned to Phe41 in a previous study. A new assignment, based on additional information from two dimensional nuclear Overhauser enhancement spectroscopy, was made to Phe152. The assignments made for the Phe41----Val variant were also used as a basis to investigate the structure of the complex formed with the aromatic donor molecule, benzhydroxamic acid. PMID- 1633808 TI - The essential active-site lysines of clostridial glutamate dehydrogenase. A study with pyridoxal-5'-phosphate. AB - Glutamate dehydrogenase (GDH) of Clostridium symbiosum, like GDH from other species, is inactivated by pyridoxal 5'-phosphate (pyridoxal-P). This inactivation follows a similar pattern to that for beef liver GDH, in which a non covalent GDH-pyridoxal-P complex reacts slowly to form a covalent complex in which pyridoxal-P is in a Schiff's-base linkage to lysine residues. [formula: see text] The equilibrium constant of this first-order reaction on the enzyme surface determines the final extent of inactivation observed [S. S. Chen and P. C. Engel (1975) Biochem. J. 147, 351-358]. For clostridial GDH, the maximal inactivation obtained was about 70%, reached after 10 min with 7 mM pyridoxal-P at pH 7. In keeping with the model, (a) inactivation became irreversible after reduction with NaBH4. (b) The NaBH4-reduced enzyme showed a new absorption peak at 325 nm. (c) Km values for NAD+ and glutamate were unaltered, although Vmax values were decreased by 70%. Kinetic analysis of the inactivation gave values of 0.81 +/- 0.34 min-1 for k3 and 3.61 +/- 0.95 mM for k2/k1. The linear plot of 1/(1-R) against 1/[pyridoxal-P], where R is the limiting residual activity reached in an inactivation reaction, gave a slightly higher value for k2/k1 of 4.8 +/- 0.47 mM and k4 of 0.16 +/- 0.01 min-1. NADH, NAD+, 2-oxoglutarate, glutarate and succinate separately gave partial protection against inactivation, the biggest effect being that of 40 mM succinate (68% activity compared with 33% in the control). Paired combinations of glutarate or 2-oxoglutarate and NAD+ gave slightly better protection than the separate components, but the most effective combination was 40 mM 2-oxoglutarate with 1 mM NADH (85% activity at equilibrium). 70% inactivated enzyme showed an incorporation of 0.7 mM pyridoxal P/mol subunit, estimated spectrophotometrically after NaBH4 reduction, in keeping with the 1:1 stoichiometry for the inactivation. In a sample protected with 2 oxoglutarate and NADH, however, incorporation was 0.45 mol/mol, as against 0.15 mol/mol expected (85% active). Tryptic peptides of the enzyme, modified with and without protection, were purified by HPLC. Two major peaks containing phosphopyridoxyllysine were unique to the unprotected enzyme. These peaks yielded three peptide sequences clearly homologous to sequences of other GDH species. In each case, a gap at which no obvious phenylthiohydantoin-amino-acid was detected, matched a conserved lysine position. The gap was taken to indicate phosphopyridoxyllysine which had prevented tryptic cleavage.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1633809 TI - S100P, a novel Ca(2+)-binding protein from human placenta. cDNA cloning, recombinant protein expression and Ca2+ binding properties. AB - A novel member of the S100 protein family, present in human placenta, has been characterized by protein sequencing, cDNA cloning, and analysis of Ca(2+)-binding properties. Since the placenta protein of 95 amino acid residues shares about 50% sequence identity with the brain S100 proteins alpha and beta, we proposed the name S100P. The cDNA was expressed in Escherichia coli and recombinant S100P was purified in high yield. S100P is a homodimer and has two functional EF hands/polypeptide chain. The low-affinity site (Kd = 800 microM), which, in analogy to S100 beta, seems to involve the N-terminal EF hand, can be followed by the Ca(2+)-dependent decrease in tyrosine fluorescence. The high-affinity site, provided by the C-terminal EF hand, influences the reactivity of the sole cysteine which is located in the C-terminal extension (Cys85). Binding to the high-affinity site (Kd = 1.6 microM) can be monitored by fluorescence spectroscopy of S100P labelled at Cys85 with 6-proprionyl-2 dimethylaminonaphthalene (Prodan). The Prodan fluorescence shows a Ca(2+) dependent red shift of the maximum emission wavelength from 485 nm to 502 nm, which is accompanied by an approximately twofold loss in integrated fluorescence intensity. This indicates that Cys85 becomes more exposed to the solvent in Ca(2+)-bound S100P, making this region of the molecule, the so-called C-terminal extension, an ideal candidate for a putative Ca(2+)-dependent interaction with a cellular target. In p11, a different member of the S100 family, the C-terminal extension which contains a corresponding cysteine (Cys82 in p11), is involved in a Ca(2+)-independent complex formation with the protein ligand annexin II. The combined results support the hypothesis that S100 proteins interact in general with their targets after a Ca(2+)-dependent conformational change which involves hydrophobic residues of the C-terminal extension. PMID- 1633810 TI - A tungsten-containing active formylmethanofuran dehydrogenase in the thermophilic archaeon Methanobacterium wolfei. AB - Methanobacterium wolfei is a thermophilic methanogenic archaeon which requires tungsten or molybdenum for growth. We have found that the organism contains two formylmethanofuran dehydrogenases, one of which is a tungsten enzyme. Indirect evidence indicates that the other formylmethanofuran dehydrogenase is a molybdenum enzyme. The tungsten enzyme was purified and characterized. The native enzyme had an apparent molecular mass of 130 kDa. SDS/PAGE revealed a composition of three subunits of apparent molecular mass 35, 51 and 64 kDa, the N-terminal amino acid sequences of two of which were determined. 0.3-0.4 mol tungsten/mol enzyme was found but no molybdenum. The pterin cofactor was identified as molybdopterin guanine dinucleotide. The purified enzyme exhibited a specific activity of 8.3 mumol.min-1.mg protein-1 and an apparent Km for formylmethanofuran and methylviologen of 13 microM and 0.4 mM, respectively. The optimum temperature for activity was 65 degrees C. At 40-60 degrees C, the rate increased with a Q10 of 1.9; the activation energy of the reaction was 45 kJ/mol. The enzyme was found to require potassium ions for thermostability. The oxygen sensitive enzyme was not inactivated by cyanide. PMID- 1633811 TI - The role of retinal in the thermal stability of the purple membrane. AB - Differential scanning calorimetry demonstrates that the bleached form of the purple membrane does not possess any measurable thermal transition in water, up to 105 degrees C, whereas in 0.1 M phosphate pH 7.5 it shows a transition at about 82 degrees C, with an enthalpy of 110 kJ/mol. In the latter medium, the native membrane shows the main transition at 97 degrees C, with an enthalpy of 390 kJ/mol. The reduced form of the purple membrane shows two small transitions in water, as well as in 0.1 M phosphate, which do not seem to be related to the main thermal transition of the native membrane. Fourier-transform infrared spectra in D2O show that the two modified samples, as well as the native one, undergo similar secondary structural changes upon thermal denaturation. These changes appear to extend through a wide temperature range for both modified forms, particularly for the bleached one. The results suggest that the main thermal transition in the purple membrane is due to a cooperative conformational change involving the disruption of the network of electrostatic and hydrogen bonding interactions which originate from the protonated Schiff base. In the two modified membranes, these conformational changes appear to proceed smoothly through a rather low or non-cooperative process. The thermal behaviour of the bleached membrane in water resembles that of the molten globule state described for several globular proteins. PMID- 1633812 TI - A rat cerebellar protein containing the cdc10/SWI6 motif. AB - Systematic analysis of soluble proteins in developing rat cerebellum by an automated two-dimensional liquid-chromatography system detected a number of proteins which increased transiently during the initial stage of postnatal development. One of the proteins, V-1, was isolated using a liquid-chromatography system, and its amino acid sequence was determined by analysis of the purified protein. The sequence showed that the V-1 protein consists of 117 amino acids with an acetylated N-terminus, and has 2.5 internal sequence repeats of 33 amino acids. Computer retrieval of the sequence indicated that the repeated sequences have a structural characteristics of the cdc10/SWI6 motif, which is found in a series of proteins, including those involved in cell-cycle control and cell-fate determination in yeast, Drosophila melanogaster and Caenorhabditis elegans. The structure of V-1, coupled with its controlled expression in early postnatal development, implies a potential role for V-1 in cerebellar morphogenesis. PMID- 1633813 TI - Prosomes and their multicatalytic proteinase activity. AB - Prosomes were first described as being mRNA-associated RNP (ribonucleoprotein) particles and subcomponents of repressed mRNPs (messenger ribonucleoprotein). We show here that prosomes isolated from translationally inactive mRNP have a protease activity identical to that described by others for the multicatalytic proteinase complex (MCP, 'proteasome'). By RNase or non-ionic detergent treatment, the MCP activity associated with repressed non-globin mRNP from avian erythroblasts, sedimenting at 35 S, could be quantitatively shifted on sucrose gradients to the 19-S sedimentation zone characteristic of prosomes, which were identified by monoclonal antibodies. The presence of small RNA in the enzymatic complex was shown by immunoprecipitation of the protease activity out of dissociated mRNP using a mixture of anti-prosome monoclonal antibodies; a set of small RNAs 80-120 nucleotides long was isolated from the immunoprecipitate. Furthermore, on CsCl gradients, colocalisation of the MCP activity with prosomal proteins and prosomal RNA was found, and no difference in the prosomal RNA pattern was observed whether the particles were fixed or not prior to centrifugation. These data indicate that the MCP activity is a property of prosomes, shown to be in part RNP and subcomplexes of in vivo untranslated mRNP. A hypothesis for the role of the prosome-MCP particles in maintaining homeostasis of specific protein levels is proposed. PMID- 1633814 TI - Detailed structural analysis of asparagine-linked oligosaccharides of the nicotinic acetylcholine receptor from Torpedo californica. AB - The structures of the major oligosaccharide moieties of the nicotinic acetylcholine receptor (AcChoR) protein from Torpedo californica have been reported [Nomoto, H., Takahashi, N., Nagaki, Y., Endo, S., Arata, Y. and Hayashi, K. (1986) Eur. J. Biochem. 157, 233-242] to be high-mannose types. Here we report detailed analyses of the structures of the remaining oligosaccharides in this receptor. The sialylated oligosaccharides released by glycopeptidase (almond) digestion were separated according to the number of sialic acid residues using high-performance anion-exchange chromatography with pulsed amperometric detection. After removal of sialic acid from each fraction, the resulting neutral oligosaccharides were separately pyridylaminated and were analyzed by a combination of sequential exoglycosidase digestion and HPLC, then identified on a two-dimensional sugar map. The structures of two desialylated pyridylamino oligosaccharides were further analyzed by high-resolution proton NMR. Each oligosaccharide was composed of species containing varying numbers of sialic acids. The desialylated complex-type oligosaccharides of AcChoR consisted of ten, eight and one different biantennary, triantennary and tetraantennary oligosaccharide, respectively. The biantennary oligosaccharides were divided into two groups; oligosaccharides with fucose at the proximal N-acetylglucosamine (six varieties) and oligosaccharides without fucose (four varieties). Each group consisted of species differing in the number of terminal galactose residues. The major component of the biantennary oligosaccharides had two galactose residues at the non-reducing termini. The terminal alpha-galactose residue(s) linked to C3 of beta-galactose were found in the fucose-containing biantennary oligosaccharides (two varieties). The triantennary oligosaccharides were also divided into two groups; oligosaccharides with (four varieties) and without (four varieties) besecting N-acetylglucosamine. These groups were composed of species differing in the number of terminal galactose residues. The major component of the triantennary oligosaccharides was fully galactosylated with three galactose residues. An unusual group, Gal beta 1-3GlcNAc, was present in low levels in the triantennary oligosaccharides. In contrast, the tetraantennary oligosaccharide was composed of only one species, which is fully galactosylated with four galactose residues. PMID- 1633815 TI - Primary-structural and evolutionary analyses of the growth-hormone gene from grass carp (Ctenopharyngodon idellus). AB - The growth-hormone (GH) gene of grass carp, one of the fastest-growing species of farmed fish, was isolated and the DNA sequenced. Only one GH gene is found in this species. This gene, which is 2.5 kb in length, has five exons and four introns, in common with all of the mammalian and the recently published common carp GH genes. In the course of vertebrate evolution, the total lengths of the intron and the non-coding region of exon 5 of the GH gene have been shortened by 40-70%, whereas the encoding exons of the gene have been slightly increased. The more closely related species exhibit the closest sequence similarity in their GH genes. For example, the similarity of the exons is 84.1-93.2% between grass carp and common carp (within the same family of Syprinedae), 43.5-82.1% between grass carp and rainbow trout (in different orders of Teleostei) and 45.8-58.6% between grass carp and rat (in different grades of Vertebrata). In addition, similar DNA domains, such as thyroid-hormone-receptor-complex-binding site and cell-type specific cis elements involved in regulation of expression of rat and human GH genes, have been localized in the corresponding regions of the grass-carp GH gene. PMID- 1633816 TI - Characterization of the promoter region of the porcine opn (osteopontin, secreted phosphoprotein 1) gene. Identification of positive and negative regulatory elements and a 'silent' second promoter. AB - Osteopontin (secreted phosphoprotein-1, Opn) is a phosphorylated glycoprotein expressed by transformed cells, macrophages, activated T-lymphocytes, specialized epithelial cells and bone cells that is characteristically enriched in milk and in the mineralized matrix of bone. The synthesis of Opn by bone cells is regulated by glucocorticoids and growth factors, which promote bone formation, and by the osteotropic hormone calcitriol (1,25-dihydroxycholecalciferol) and retinoic acid, which mediate bone resorption, indicating a bifunctional role for this protein in bone remodelling. To study the transcriptional regulation of the opn gene, two genomic clones (10 and 15 kb) encoding the opn gene were isolated from a porcine liver genomic library cloned into lambda phage. From the 15-kb clone a 4-kb EcoRI fragment containing the first two exons and 2.6 kb of the 5' flanking region of the opn gene was sequenced, and the transcriptional start site determined by primer extension analysis and S1 nuclease mapping. To identify the opn promoter, chimeric chloramphenicol acetyltransferase constructs were prepared using fragments from the first intron and the 5' flanking region of the opn gene. Transient transfection of porcine bone cells with these constructs showed strong promoter activity located within 74 bp upstream from the transcription initiation site. Within this region a TATA sequence, TTTAAA, was identified at positions -26 to -31. However, the highest transcription rate was observed in a construct extending 180 bp upstream that included a CCGCCC Sp1 binding sequence (-63 to 68), and an AP1 site (-74 to -80). Further upstream in the 5' flanking region and within the first intron of the opn, a number of consensus sequences could be identified. Chimeric constructs containing a GGGTCAtatGGTTCA direct repeat consensus sequence for a vitamin D3 response element located at nucleotides -2245 to -2259 responded to the addition of 0.1 microM calcitriol by a 2.5-fold stimulation of transcription, although a greater than 2-fold increase was also observed in shorter constructs -180 to -905 lacking such a consensus sequence. Promoter activity was also exhibited by a region containing a TTTAAA sequence in the first intron that corresponded to the putative promoter site reported for mouse opn in macrophages (Miyazaki, Y., Setoguchi, M., Yoshida, S., Higuchi, Y., Akizuki, S. & Yamamoto, S. (1990) J. Biol. Chem. 265, 14432-14438).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1633817 TI - O-glycosylation and stability. Unfolding of glucoamylase induced by heat and guanidine hydrochloride. AB - We have examined the stabilities of the catalytic and binding domains of glucoamylase 1 from Aspergillus niger and how these stabilities are affected by the O-glycosylated linker glycopeptide which separates the domains. On heating, the catalytic domain unfolds irreversibly, whereas the binding domain unfolds reversibly as shown by differential scanning calorimetry and by 1H NMR. The stability of three functional peptides, derived from glucoamylase 1, containing the binding domain alone and with 10 or 38 residues of the linker glycopeptide [Williamson, G., Belshaw, N.J. and Williamson, M. (1992) Biochem. J. 282, 423 428] was examined. Refolding in each case was reversible after thermal or chemical denaturation. beta-Cyclodextrin stabilised the binding domain by the same amount when it was part of glucoamylase 1 or an isolated domain. The thermal stability of the catalytic domain was not affected by the binding domain; however, the catalytic domain increased the melting temperature of the binding domain. Furthermore, the linker glycopeptide stabilised the binding domain against reversible thermal and chemical denaturation by about 10 kJ/mol, but only a portion of the O-glycosylated residues were required for stabilisation. On a simple molecular mass basis, the linker glycopeptide does not contribute as much as expected to the denaturational enthalpy of glucoamylase 1 and, in addition, shows only a small conformational change on chemical or thermal denaturation; this supports an extended structure for the linker. The results demonstrate that the unfolding pathway of glucoamylase 1 depends on the concentration of beta cyclodextrin and that the presence of the catalytic domain and/or the linker glycopeptide stabilises the binding domain. PMID- 1633818 TI - The chloroplast-targeting domain of plastocyanin transit peptide can form a helical structure but does not have a high affinity for lipid bilayers. AB - Conformational properties and interactions with lipid membranes were studied for the chemically synthesized peptides PC(1-37) and PC(1-43), corresponding to the N terminal 37 and 43 residues, respectively, of the transit peptide of the precursor to plastocyanin of Silene pratensis. PC(1-43) covers the entire chloroplast targeting domain of the transit peptide. CD spectra of PC(1-37) and PC(1-43) showed that both peptides have little ordered structure in aqueous solutions but form partially helical conformations in the presence of detergent micelles or in methanol. Vesicle disruption and direct-binding experiments revealed, however, that neither PC(1-37) nor PC(1-43) had a high affinity for lipid membranes. Since in the intact plastocyanin transit peptide the chloroplast targeting domain is followed by a hydrophobic thylakoid-transfer domain, the plastocyanin precursor may well be transported to the chloroplast surface first with the aid of the thylakoid-transfer domain. The chloroplast-targeting domain may then form a helical structure in the lipid environments, and a chloroplast specific motif displayed on the helical structure may be recognized by a receptor protein located at the chloroplast envelope membranes. PMID- 1633819 TI - Determination of DNA-binding parameters for the Bacillus subtilis histone-like HBsu protein through introduction of fluorophores by site-directed mutagenesis of a synthetic gene. AB - A synthetic gene encoding the histone-like DNA-binding protein HBsu from Bacillus subtilis has been expressed in Escherichia coli. Yields of the purified protein are at least 20 mg/l culture medium. The recombinant HBsu protein is chromatographically, immunologically and functionally identical with the authentic wild-type protein. N-terminal sequencing of the purified protein confirms the fidelity of expression of the synthetic gene in E. coli. Site directed mutagenesis of the synthetic gene was employed to replace several amino acid residues of HBsu protein with tryptophan to facilitate the determination of DNA-binding parameters by fluorescence spectroscopy. According to gel-retardation experiments, the mutant protein [Phe47----Trp]HBsu shows identical DNA binding to wild-type HBsu protein. Analysis of fluorescence binding data reveals that [Phe47 ---Trp]HBsu binds double-stranded DNA with a dissociation constant in the micromolar range. Computer-assisted fit of binding models to the experimental data renders positive cooperativity of binding unlikely. A dimer of [Phe47--- Trp]HBsu appears to contact three or four base pairs of DNA. These results are in partial disagreement with earlier measurements on closely homologous proteins which tended to show cooperative binding and a longer DNA contact region. PMID- 1633820 TI - In vivo and in vitro characterization of overproduced colicin E9 immunity protein. AB - We report the overproduction of the immunity protein for the DNase colicin E9 and its characterization both in vivo and in vitro. The genes for colicin immunity proteins are normally co-expressed from Col plasmids with their corresponding colicins. In the context of the enzymatic colicins, the two proteins form a complex, thereby protecting the host bacterium from the antibiotic activity of the colicin. This complex is then released into the medium, whereupon the colicin alone translocates (through the appropriate receptor) into sensitive bacterial strains, resulting in bacterial cell death. The immunity protein for colicin E9 (Im9) has been overproduced in a bacterial host in the absence of its colicin, to enable sufficient material to be isolated for structural studies. As a prelude to such studies, the in-vivo and in-vitro properties of overproduced Im9 were analysed. Electrospray mass spectrometry verified the molecular mass of the purified protein and analytical ultracentrifugation indicated that the native protein approximates a symmetric monomer. Fluorescence-enhancement and gel filtration experiments show that purified Im9 binds to colicin E9 in a 1:1 molar ratio and that this binding neutralizes the DNase activity of the colicin. These results lay the foundations for a full biophysical and structural characterization of the colicin E9 DNase inhibitor protein, Im9. PMID- 1633821 TI - The GppNHp-activated adenylyl cyclase complex from turkey erythrocyte membranes can be isolated with its beta gamma subunits. AB - The adenylyl cyclase complex, derived from turkey erythrocyte membranes, was activated using guanosine 5'-[beta, gamma-imido]triphosphate (Gpp[NH]p) and separated under low-detergent and low-salt conditions using conventional molecular-sieve chromatography followed by high-pressure ion-exchange and molecular-sieve chromatography. Although the complex remains activated with Gpp[NH]p throughout the isolation, the beta gamma subunits copurify with the cyclase. The stoichiometry of the cyclase to the alpha subunit of the stimulatory guanosine-nucleotide-binding regulatory protein (alpha s) to the beta subunit is close to unity, demonstrating that the beta gamma subunits do not dissociate from the Gs.cyclase complex (Gs, guanosine-nucleotide-binding regulatory protein) upon activation of the enzyme. If the final purification step was performed at high salt concentrations, the beta gamma subunits could be separated from the alpha s.cyclase complex. Previously reported results on bovine brain cyclase also showed that the Gs.cyclase complex remains intact subsequent to activation by hormone and Gpp[NH]p [Marbach, I., Bar-Sinai, A., Minich, M. and Levitzki, A. (1990) J. Biol. Chem. 265, 9999-10,004]. These results, using adenylyl cyclase from two different sources, support our previous kinetic experiments which first suggested that beta gamma subunits are not released from Gs upon cyclase activation. We, therefore, argue that the mode of adenylyl cyclase inhibition by the inhibitory guanosine-nucleotide-binding regulatory protein cannot be via shifting the alpha s to beta gamma equilibrium as is commonly believed, and an alternate hypothesis is proposed. PMID- 1633822 TI - Novel aerobic 2-aminobenzoate metabolism. Nucleotide sequence of the plasmid carrying the gene for the flavoprotein 2-aminobenzoyl-CoA monooxygenase/reductase in a denitrifying Pseudomonas sp. AB - Pseudomonas KB 740 degrades 2-aminobenzoate aerobically via a chimeric pathway which combines characteristics of anaerobic and aerobic aromatic metabolism. Atypically, 2-aminobenzoyl-CoA is an intermediate, and the activated aromatic acid is not only hydroxylated but also reduced to an alicyclic compound in a single step. The bacterial strain possesses a small plasmid, pKB 740, which carries all essential information of this new pathway. Its total nucleotide sequence was determined. It consists of 8280 bp and contains the genes for the two initial enzymes of the pathway; 2-aminobenzoate-CoA ligase catalyzes the activation of the aromatic acid, and the flavoenzyme 2-aminobenzoyl-CoA monooxygenase/reductase catalyzes the hydroxylation (monooxygenase activity) and subsequent reduction (reductase activity) of the aromatic ring of 2-aminobenzoyl CoA. Furthermore, five open reading frames (ORF) possibly coding for polypeptides are on the plasmid. Putative promoter sequences were found for two of the ORF. A nucleotide sequence able to form a possible termination loop was located downstream of the gene for 2-aminobenzoyl-CoA monooxygenase/reductase. This gene consists of 2190 bases. The deduced amino acid sequence of the protein (730 residues; calculated molecular mass of the native 729-residue protein, 83,559 Da) contains a consensus sequence for an FAD-binding site at the N-terminus and a possible NAD(P)H-binding site approximately 150 amino acid residues apart from the N-terminus. The monooxygenase/reductase shows low sequence similarity to the flavoprotein salicylate hydroxylase. Functional and evolutionary aspects of this work are discussed. PMID- 1633823 TI - Photochemical trapping of a bacteriopheophytin anion in site-specific reaction center mutants from the photosynthetic bacterium Rhodobacter sphaeroides. AB - The mutant YY in the reaction center of Rhodobacter sphaeroides, in which Phe181 on the L chain has been replaced by Tyr, and the double mutant FY, with Tyr210 on the M chain replaced by Phe and Phe181 on the L chain replaced by Tyr, have been constructed by site-directed mutagenesis. The studies described here were performed to complement a previous mutational analysis of mutant FF with Tyr210 replaced by Phe. Both new strains grow photoheterotrophically. The optical absorption spectra of reaction centers isolated from these mutants have band shifts attributable to the monomer bacteriochlorophylls in the vicinity of the substitutions. Photochemical trapping of the bacteriopheophytin anion (I-) indicates that the bacteriopheophytin on the B branch is reduced to a much greater extent in FF and FY as compared to YY and wild-type YF. Low temperature (77 K) absorption spectra clearly show that in the wild-type (YF) and YY reaction centers only the 545-nm-absorbing bacteriopheophytin is reduced while in the FF and FY reaction centers both the 535-nm and 545-nm-absorbing bacteriopheophytins are reduced. A simple kinetic analysis is used to explain these results. This analysis suggests that, in order for the observed trapping results to occur, a decrease in the 'cycling' time must take place, that is changes in the rate(s) of charge recombination must accompany the already known decrease in the forward electron transfer rate. PMID- 1633824 TI - A mutation at Gly314 of the beta subunit of the Escherichia coli pyridine nucleotide transhydrogenase abolishes activity and affects the NADP(H)-induced conformational change. AB - Escherichia coli RH1 contains a mutation causing complete loss of pyridine nucleotide transhydrogenase activity. A single base change in the chromosomal DNA resulted in the replacement of Gly314 of the beta subunit by a Glu residue. The mutant enzyme was partially purified and its trypsin cleavage products examined. The distinct pattern of polypeptides given by proteolysis of the normal transhydrogenase in the presence of NADP(H) was absent when the mutant enzyme was treated with trypsin. However, the beta subunit of the mutant enzyme retained its ability to bind to NAD-agarose. Further substitutions were made at Gly314 converting it to Ala, Val or Cys by the use of site-directed mutagenesis. All substitutions for Gly314 abolished the activity completely. The enzyme containing the Gly314----Ala mutation was studied in detail and behaved exactly as the enzyme containing the Gly314----Glu mutation. It is concluded that the mutation in the beta subunit abolished the NADP(H)-induced conformational change in the mutant enzyme. This conformational change, caused by NADP(H) binding, is required to cleave the normal beta subunit at Arg265 by trypsin. The genes encoding the pyridine nucleotide transhydrogenase were completely resequenced and several corrections have been made to the previously published sequence [Clarke et al. (1986) Eur. J. Biochem. 158, 647-653]. PMID- 1633825 TI - Evidence that rat liver mitochondrial and cytosolic fumarases are synthesized from one species of mRNA by alternative translational initiation at two in-phase AUG codons. AB - Rat liver contains two isozymes of fumarase, mitochondrial and cytosolic enzymes. Recently, we suggested that the precursors of both isozymes might be synthesized by one species of mRNA [Suzuki, T., Sato, M., Yoshida, T. & Tuboi, S. (1989) J. Biol. Chem. 264, 2581-2586]. To examine this possibility, we have isolated and characterized rat genomic clones for fumarase. The isolated clones covered almost all of the 5' half of the fumarase gene consisting of five exons. The first exon contained the whole 5' non-coding region and the signal peptide of mitochondrial precursor. The second exon encoded 45 amino acid residues of both mature proteins, starting from the N-terminal alanine. By using the boundary region of the first intron and the second exon as an S1-nuclease-analysis probe, we obtained conclusive evidence that rat liver contains no other mRNA specific for the cytosolic isozyme of fumarase. Two transcription-initiation sites were identified by further S1-nuclease-mapping analysis and were shown to be located very close to each other, differing by only four bases in length. Therefore, these sites were considered to be functionally the same. The results obtained by hybrid-selected translation, with a DNA fragment of the 5' non-coding region as a hybridization probe for selecting mRNA, were consistent with the above findings. We found a plausible secondary structure within the 5' non-coding mRNA sequence that may impede initiation and so alter the efficiency of translation. We also discuss the mechanism regulating translational initiation. PMID- 1633826 TI - The serine-protease inhibitor of cartilage matrix is not a chondrocytic gene product. AB - Human articular cartilage contains significant amounts of antileukoprotease, a cationic low-molecular-mass serine-protease inhibitor, which was originally purified from mucous secretions (synonym: secretory leukocyte proteinase inhibitor). As it was not known whether the inhibitor molecule is also synthesized locally, we investigated antileukoprotease gene expression in chondrocytes. No antileukoprotease-specific mRNA was detected in adult or foetal human chondrocytes by in situ hybridization, Northern-blot analysis or polymerase chain reaction. Concurrently, the chondrocytes remained unstained on immunohistology, whereas immunoreactive antileukoprotease was demonstrated in the cartilage matrix. By Northern-blot analysis, the antileukoprotease message was detected in the promyelocytic cell line HL60, the myelomonocytic cell line U937 and even in mature polymorphonuclear leukocytes from the peripheral blood of healthy donors. Immunoperoxidase staining of polymorphonuclear leukocytes for the antileukoprotease protein indicated that this cell is likely to be the physiological source of the inhibitor in serum. The results further suggest an accumulation of the inhibitor in the cartilage matrix. PMID- 1633827 TI - The structure of neutral protease from Bacillus cereus at 0.2-nm resolution. AB - The crystal structure of the neutral protease from Bacillus cereus has been refined to an R factor of 17.5% at 0.2-nm resolution. The enzyme, an extracellular metalloendopeptidase, consists of two domains and binds one zinc and four calcium ions. The structure is very similar to that of thermolysin, with which the enzyme shares 73% amino-acid sequence identity. The active-site cleft between the two domains is wider in neutral protease than in thermolysin. This suggests the presence of a flexible hinge region between the two domains, which may assist enzyme action. The high-resolution analysis allows detailed examination of possible causes for the difference in thermostability between neutral protease and thermolysin. PMID- 1633828 TI - X-ray absorption spectroscopy of soybean lipoxygenase-1. Influence of lipid hydroperoxide activation and lyophilization on the structure of the non-heme iron active site. AB - X-ray absorption spectra at the Fe K-edge of the non-heme iron site in Fe(II) as well as Fe(III) soybean lipoxygenase-1, in frozen solution or lyophilized, are presented; the latter spectra were obtained by incubation of the Fe(II) enzyme with its product hydroperoxide. An edge shift of about 2-3 eV to higher energy occurs upon oxidation of the Fe(II) enzyme to the Fe(III) species, corresponding to the valence change. The extended X-ray absorption fine structure shows clear differences in active-site structure as a result of this conversion. Curve fitting on the new data of the Fe(II) enzyme, using the EXCURV88 program, leads to a coordination sphere that is in agreement with the active-site structure proposed earlier (6 +/- 1 N/O ligands at 0.205-0.209 nm with a maximum variance of 0.009 nm, including 4 +/- 1 imidazole ligands) [Navaratnam, S., Feiters, M. C., Al-Hakim, M., Allen, J. C., Veldink, G. A. and Vliegenthart, J. F. G. (1988) Biochim. Biophys. Acta 956, 70-76], while for the Fe(III) enzyme a shortening in ligand distances occurs (6 +/- 1 N/O ligands at 0.200-0.203 nm with maximum variance of 0.008 nm) and one imidazole is replaced by an oxygen ligand of unknown origin. Lyophilization does not lead to any apparent differences in the iron coordination of either species and gives a much better signal/noise ratio, allowing analysis of a larger range of data. PMID- 1633829 TI - Biochemical analysis of the biogenesis and function of the Escherichia coli export factor SecY. AB - SecY is an integral plasma-membrane protein of Escherichia coli which is essential for the export of periplasmic and outer-membrane proteins containing cleavable signal sequences. We have synthesized SecY in vitro using an E. coli transcription/translation system. In the absence of membranes, SecY remained largely soluble but cosedimented on sucrose gradients with the membrane fraction when inside-out plasma-membrane vesicles (INV) had been added cotranslationally. Membrane association of SecY was unaffected if the endogenous SecY of the INV had been inactivated by either antibodies, a mutation or trypsin treatment. In contrast, inactivation of the INV SecY interfered with membrane targeting and, consequently, the processing of precursors to beta-lactamase and lambda receptor. When SecY-deprived INV were, however, first functionally reconstituted with in vitro-synthesized SecY, targeting and translocation of the lambda receptor were partially restored. Thus, the assembly of SecY into INV in vitro leads to an active enzyme. In addition, we show that the prlA4 allele of the secY gene suppresses signal-sequence mutations of the lambda receptor in vitro. Collectively, our results demonstrate that SecY, while functioning as a membrane located receptor for precursors of exported proteins, appears to be virtually independent of pre-existing SecY for its own membrane integration. PMID- 1633830 TI - Expression of recombinant soluble and membrane-bound catechol O-methyltransferase in eukaryotic cells and identification of the respective enzymes in rat brain. AB - The rat and human recombinant soluble and membrane-bound catechol O methyltransferase (S- and MB-COMT, respectively) were expressed using mammalian and baculovirus vectors. Low levels of rat and human S-COMT polypeptides were detected by immunoprecipitation in K-562 cell lines transfected with the S-COMT vectors. From K-562 cells transfected with the rat MB-COMT construct, both S- and MB-COMT recombinant proteins were detected by a rat COMT-specific anti-serum. Infection of lepidopteran Spodoptera frugiperda cells with recombinant S- or MB COMT baculovirus constructs yielded high amounts of enzymically active and immunoreactive S- or MB-COMT proteins, respectively. Pulse/chase experiments with [35S]methionine-labelled insect cells infected with the MB-COMT baculovirus showed that the 30-kDa recombinant human MB-COMT polypeptide was not processed into the 25-kDa S-COMT form. Subcellular fractionations of insect cells, followed by immunoblotting with COMT antiserum, showed that recombinant S-COMT was found only in the soluble, cytoplasmic fraction, whereas MB-COMT resided both in soluble and membrane fractions. The recombinant MB-COMT sedimented in Percoll gradients at the density of 1.042 g/ml cosedimenting with the plasma-membrane marker. Fractionation and immunoblotting experiments on homogenized total rat brains indicated that the rat S-COMT (24 kDa) and some of the rat MB-COMT (28 kDa) was recovered in soluble fractions, whereas the microsomal material having COMT activity contained the MB-COMT polypeptide. The rat brain microsomal MB-COMT had a density of 1.042 g/ml in Percoll gradients, cosedimenting with the plasma membrane and rough-endoplasmic-reticulum marker enzymes. The meta/para methylation ratio of dihydroxybenzoic-acid substrate by different recombinant and rat brain COMT-containing subcellular fractions was analysed. PMID- 1633831 TI - Classification of dynamical diseases by new mathematical tools: application of multi-dimensional phase space analyses to the pulsatile secretion of parathyroid hormone. AB - The biological importance of dynamic hormonal secretion has been demonstrated. There is good evidence from recent studies that parathyroid hormone (PTH) which plays an important role in bone physiology is secreted in a pulsatile manner. In this study we performed a classification of two 'dynamical diseases' namely osteoporosis and hyperparathyroidism by the visualization of dynamic PTH secretion in multidimensional phase spaces. PMID- 1633832 TI - Verapamil increases serum ionized calcium and serum phosphate in patients with post-surgical hypoparathyroidism. AB - The calcium homeostasis in eight patients with postoperative hypoparathyroidism was examined before and after 2 weeks of administration of verapamil in an oral dose of 80 mg three times daily. Serum ionized calcium increased during verapamil treatment (from mean +/- SD of 1.10 +/- 0.06 to 1.24 +/- 0.38 mmol l-1; P less than 0.05), as well as total serum calcium corrected for protein (from 2.11 +/- 0.13 to 2.18 +/- 0.13 mmol l-1; P less than 0.05). During treatment with verapamil there was an increase in serum phosphate (from 1.08 +/- 0.15 to 1.19 +/ 0.20 mmol l-1 P less than or equal to 0.05) and in the urinary excretion of phosphate (P/creatinine ratio from 1.22 +/- 0.69 to 1.83 +/- 0.97; P less than or equal to 0.05). The serum 1,25-dihydroxyvitamin-D3 and serum parathyroid hormone were below the detection limits both before and after verapamil treatment. There were no significant changes either of the intestinal absorption of calcium or of the urinary calcium excretion. Serum osteocalcin was insignificantly reduced after treatment (1.60 +/- 0.70 before treatment and 1.25 +/- 0.71 micrograms l-1 after treatment). Thus in patients with post-surgical hypoparathyroidism verapamil has effects on calcium and phosphorous homeostasis. Since calcium absorption was not influenced by verapamil, it is suggested that verapamil affects bone mineral metabolism. PMID- 1633833 TI - Effects of cholestyramine and acipimox on subfractions of plasma low density lipoprotein. Studies in normolipidaemic and hypercholesterolaemic subjects. AB - Two independent studies were designed to investigate the separate and combined effects of acipimox and cholestyramine on plasma low density lipoprotein subfractions. In the first study, normolipidaemic subjects were given cholestyramine (16 g day-1, 4 weeks), followed, after an 8-week wash-out period, by acipimox (750mg day-1, 4 weeks). In the second study, moderately hypercholesterolaemic subjects were prescribed acipimox (1250mg day-1, 10 weeks), followed by acipimox in combination with low dose cholestyramine (12g day-1) for a further 10 weeks. In the normal subjects, cholestyramine decreased total LDL mass (density (d) = 1.019-1.063g ml-1) by selectively reducing the largest, least dense LDL-I (d 1.025-1.034 g ml-1, P less than 0.05) and LDL-II (d 1.034-1.044 g ml-1, P less than 0.005) subfractions. The small, dense LDL-III (d 1.044-1060 g ml-1) showed a variable response to the resin. In the same subjects acipimox produced no overall change in total LDL mass but showed a tendency to redistribute LDL towards LDL-I (+10%) and LDL-II (+10%) in a manner related to the changes in plasma triglyceride (TG) (TG vs. LDL-III r = 0.75, P less than 0.05). In the hypercholesterolaemic subjects acipimox induced a substantial redistribution of LDL subfractions (LDL-I +84% P less than 0.05; LDL-III -50%) without affecting total LDL mass. The addition of cholestyramine produced a significant decrease in total LDL mass which was again confined to the LDL-I ( 28%) and LDL-II (-23%) subfractions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1633834 TI - Functional and structural determinants of glomerulosclerosis in the fawn-hooded rat. AB - The effect of uninephrectomy (UN) at 4 months of age was studied on several parameters involved in the development of glomerulosclerosis (GS) in male spontaneously hypertensive Fawn-Hooded rats. Protein excretion per animal was significantly more increased in UN rats at 2 months after operation compared to sham operated controls (202 +/- 104 vs. 88 +/- 37 mg 24 h-1, P = 0.005) and remained significantly higher throughout the rest of the observation period. At 11 months of age UN rats had a marked increase in the incidence of GS, 37 +/- 16% compared to 5 +/- 3% (P less than 0.001) in controls. No differences were observed in mean arterial blood pressure. Functional studies in separate groups of rats at 5 months of age showed an increase in single kidney glomerular filtration rate in UN rats (0.40 +/- 0.07 vs. 0.28 +/- 0.09 ml min-1 100 g, P = 0.006). Single kidney renal plasma flow and filtration fraction were not altered. Mean glomerular volume was increased 1 month after UN (1.86 +/- 0.25 vs. 1.39 +/- 0.25 x 10(6) microns 3, P = 0.003). Urinary noradrenaline excretion per animal (24-h) showed a high sympathic nervous tone in both sham and UN rats. Total urinary dopamine and kallikrein excretion per animal were not influenced by UN. These data indicate that after UN the development of GS in this rat strain is accelerated in association with compensatory hyperfiltration and glomerular volume expansion, which may play a role in the pathogenesis of GS. PMID- 1633835 TI - Identification of the defective NADPH-oxidase component in chronic granulomatous disease: a study of 57 European families. AB - Chronic Granulomatous Disease (CGD) manifests as a predisposition to infection as a result of defective function of the NADPH oxidase of phagocytic cells. Proteins identified as part of this system include two subunits of a cytochrome b (cytochrome b-245) and two cytosolic factors. The affected oxidase component was determined in 63 CGD patients from 57 families, by Western blotting of extracts of their neutrophils with antibodies to those proteins. 38 (67%) of the families were X-linked with a defect of the beta subunit of the cytochrome. 13 (23%) lacked p47-phox, 3 (5%) p67-phox, and 3 (5%) the alpha subunit of the cytochrome. PMID- 1633836 TI - Sustained high plasma 5-aminolaevulinic acid concentration in a volunteer: no porphyric symptoms. AB - The pathogenesis of the acute porphyric attack is not known. One hypothesis is that porphyrin precursors, especially 5-aminolaevulinic acid (ALA), are toxic for neuronal tissue. This was tested by infusing ALA in a male volunteer after a loading dose at a rate of 50-80 mg h-1 for 92.5 h. During the experiment plasma ALA concentration was 9-11 mumol 1-l and porphobilinogen concentration 3-6 mumol 1-l which are the levels seen during acute attacks. Urinary excretion of these porphyrin precursors was also markedly increased. ALA infusion caused no subjective symptoms and no change in pulse rate, blood pressure, or autonomic nerve function or conduction velocity of peripheral nerves. Photosensitivity was not demonstrable. It is concluded that sustained high plasma ALA concentration does not cause porphyria-like symptoms. PMID- 1633837 TI - Influence of clinical findings, positional manoeuvres, and systolic ankle arterial pressure on transcutaneous oxygen tension in peripheral arterial occlusive disease. AB - The mutual effects of systolic ankle arterial pressures, positional manoeuvres, and calf artery occlusions on transcutaneous oxygen partial pressures (tcpO2) were studied in 388 legs of 258 patients with peripheral arterial occlusive disease (PAOD). The tcpO2-vs-perfusion pressure relationship could be satisfactorily fitted by a non-linear regression model deduced from the tcpO2 theory. Flow-insensitive ranges of tcpO2-vs-flow hyperbolas were reduced by both leg lowering and moving the electrode towards proximal measuring sites. Lower tcpO2 values were found in case of occluded compared to patent calf arteries at ankle arterial pressure indices below 0.4. The tcpO2 positional variability increased with worsening hemodynamic compensation and was most pronounced in critical limb ischaemia (ischaemic rest pain, non-healing ulcerations). According to a retrospective analysis, a critical ischaemia could be assumed if supine and sitting tcpO2-values exceed neither 10 nor 45 mmHg, respectively. PMID- 1633838 TI - Antibodies to cathepsin G in Crohn's disease. AB - Antibodies directed against antigens in human neutrophils have proved to be of great diagnostic value in certain systemic vasculitides. Recent reports have focused the attention on these antigens as targets of antibodies in sera of patients with inflammatory bowel disease. We investigated the sera drawn from 60 patients suffering from biopsy proven Crohn's disease and 15 patients with active ulcerative colitis. Using sensitive enzyme-linked immunosorbent assays with purified antigens and Western blotting the following antibodies could be demonstrated: cathepsin G (cat-G) antibodies IgG 38.3%, IgM 13.3%, IgA 23.3% and antibodies against human leucocyte elastase (HLE) IgG, IgA, IgM 3.3%. Low but significant correlations could be found for cat-G antibodies (IgG) and the van HEES index of activity. 73.9% of the cat-G (IgG) positive patients had colon involvement. In the sera of patients with ulcerative colitis no antibodies to cat G or HLE were detectable. Only 8.3% of the patients with Crohn's disease had antibodies against proteinase 3 (C-ANCA). Our data indicate that cat-G among other myeloid lysosomal enzymes seems to be an important target antigen of antibodies in sera of patients with Crohn's disease. Cat-G antibodies might be helpful to distinguish Crohn's disease from ulcerative colitis. PMID- 1633839 TI - Attempts to accelerate glucagon absorption: effects of adding a vasodilator and of injection using a 'sprinkler' needle. AB - Glucagon injected subcutaneously or intramuscularly may take up to 30 min to reverse hypoglycaemia. We investigated whether glucagon absorption could be accelerated by two manoeuvres known to enhance insulin absorption: addition of a powerful local hyperaemic agent (10 nmole alpha-calcitonin gene-related peptide; CGRP), and injection using a multihole 'sprinkler' needle. Glucagon (1 mg) given by conventional injection to six normal subjects produced peak plasma glucagon concentrations of 1.48 +/- 0.23 (SEM) ng ml-1 after 20 min and a peak glycaemic response of 7.8 +/- 0.8 mmol l-1 at 25 min. Glucagon injected with CGRP or using the sprinkler needle did not produce any significant differences in plasma glucagon or glycaemia profiles, compared with conventional injection. Further studies demonstrated that glucagon is itself a powerful vasodilator, causing a 300-500% increase in local blood flow, comparable to that induced by CGRP. Because of its intense local hyperaemic action, the absorption of subcutaneously injected glucagon may be optimal and seems unlikely to be accelerated by pharmacological or other means. PMID- 1633840 TI - Order and disorder in 30 nm chromatin fibers. AB - The tendency of DNA to form fibers upon condensation with counterions is reviewed. It is shown that chromatin fibers may acquire a relatively constant diameter of about 30 nm simply as an optimal size achieved upon neutralization of DNA, without requiring a repetitive internal structure. Thus the size of chromatin fibers would not be determined by any specific spatial interaction between DNA and histones. The driving force for the formation of fibers in chromatin would be similar to that found in proteins when they acquire a compact globular shape. PMID- 1633841 TI - Different sequence environments of cysteines and half cystines in proteins. Application to predict disulfide forming residues. AB - Protein sequences are often derived by translating genetic information, rather than by classical protein sequencing. At the DNA level cysteines and half cystines are indistinguishable. Here we show that the sequential environments of 'free' cysteine and half cystine are different. A possible origin of this difference is discussed and a simple method to predict cysteines and half cystines from the amino acid sequence is also presented. PMID- 1633842 TI - Isolation and characterization of the MHC linked beta-type proteasome subunit MC13 cDNA. AB - We have cloned and analysed the second mouse MHC-linked proteasome subunit, designated MC13, which appears to be homologous to the human RING10 proteasome protein. The isolated cDNA has an ORF encoding a protein of 276 amino acids with a molecular weight of ca. 30 kDa. Sequence alignment reveals that the subunit MC13 and several other mammalian proteasome subunits are encoded by a second proteasome gene family. This second gene family encodes subunits of the beta type, reveals striking sequence similarities with the beta-subunit of archaebacterial proteasomes and is related to, but distinct from, the genes encoding the so-called alpha-type subunits. PMID- 1633843 TI - Evidence that dopachrome tautomerase is a ferrous iron-binding glycoprotein. AB - Dopachrome tautomerase (DT) (EC 5.3.2.3) is a melanocyte-specific, membrane associated, heat-labile, non-dialyzable, protease-sensitive factor which catalyzes the isomeric rearrangement of dopachrome to 5,6-dihydroxyindole-2 carboxylic acid (DHICA), apparently through a tautomerization reaction. Metal ions such as Cu, Ni, Co, Zn, Mn, Ca, Al, and Fe can also catalyze the dopachrome/DHICA isomerization. How is the reaction regulated in vivo? An attractive possibility would be that DT is a metalloenzyme. Here we present evidence that this may indeed be the case. Purified preparations of DT and tyrosinase, obtained from Cloudman S91 mouse melanoma cells, were assayed in the presence of a variety of metal chelators including EDTA (predominantly Ca and Mg), EGTA (predominantly Ca), phenylthiourea (PTU) (predominantly Cu), 2,2' dipyridyl (predominantly Fe); 1,10-phenanthroline (predominantly Fe), and 2,3 dihydroxybenzoic acid (predominantly Fe). In addition, DT activity was assayed in the presence of two non-chelating structural analogs of 1,10-phenanthroline. Results were as follows: (i) iron chelators inhibited DT activity with no effects on tyrosinase activity; (ii) inhibition by the chelators was reversible with the addition of ferrous iron; (iii) 1,10-phenanthroline pre-complexed to ferrous iron was not inhibitory to DT; (iv) non-chelating analogs of phenanthroline were not inhibitory to DT; (v) PTU was inhibitory to tyrosinase but not DT; (vi) Ca2+ and Mg2+ chelators had little effect on either enzyme activity. Finally, studies with glycosylation inhibitors, glycosylase enzymes, and immobilized lectins, indicated that DT is a glycoprotein. The results suggest that DT is a metal-containing glycosylated enzyme, possibly with ferrous iron at its catalytic center. PMID- 1633844 TI - The oligosaccharides in a recombinant hepatitis B virus surface antigen (HBsAg) carrying the pre-S2 region derived from yeast. AB - The N- and O-linked oligosaccharides in a yeast-derived HBsAg M protein (pre-S2 + S) were analyzed. Two major structures of the N-linked oligosaccharides bound to residue Asn4 were determined to be high-mannose type oligosaccharides, Man7GlcNAc2 and Man8GlcNAc2, by two-dimensional sugar mapping of the corresponding pyridylamino oligosaccharides. Peptide mapping of the M protein, sequence analysis of the glycopeptides after beta-elimination under reducing conditions and sugar-composition analysis revealed that the O-linked oligosaccharides were composed solely of mannose and bound to residue Ser5, Thr6, Thr7, Ser27, Ser28, Ser29 and Thr31 in the pre-S2 region. PMID- 1633845 TI - Effective detergent/lipid ratios in the solubilization of phosphatidylcholine vesicles by Triton X-100. AB - Effective detergent:lipid ratios (i.e. molar ratios in the mixed aggregates, vesicles or micelles) have been estimated for the solubilization of phosphatidylcholine vesicles by Triton X-100. Effective molar ratios are given for both the onset and the completion of bilayer solubilization; small unilamellar, large unilamellar and multilamellar vesicles have been used. Effective detergent:lipid ratios are independent of phospholipid concentration, and their use allows a deeper understanding of membrane-surfactant interactions. PMID- 1633846 TI - Identification and characterization of two dermorphins from skin extracts of the Amazonian frog Phyllomedusa bicolor. AB - Skin extracts of South American hylid frogs of the subfamily Phyllomedusinae contain dermorphins and deltorphins, opioid heptapeptides highly selective for either mu or delta receptors. In all these peptides, a D-amino acid is present in the second position. The structure of the precursors for Ala-deltorphins was recently deduced from cloned cDNAs derived from skin of Phyllomedusa bicolor (Richter et al. (1990) Proc. Natl. Acad. Sci. USA 87, 4836-4839). From the amino acid sequence of these precursors, the existence of three peptides related to dermorphin could be predicted. From methanol extracts of skin of Ph. bicolor we have isolated two of these peptides, [Lys7]dermorphin-OH and [Trp4,Asn7]dermorphin-OH. The biological activity of these new dermorphins and their amidated counterparts is presented. PMID- 1633847 TI - Oligo(2'-O-methyl)ribonucleotides. Effective probes for duplex DNA. AB - To find novel probes for duplex DNA, we prepared four types of triplexes containing a homopurine-homopyrimidine 15-mer duplex DNA, and examined their thermal stabilities (Tm values). The single strand used for triplex formation were a DNA 15-mer having a defined C-T mixed sequence, and its sugar-modified analogs, namely 2'-fluoro DNA, RNA, and 2'-O-methyl RNA. The 2'-O-methyl RNA and the RNA-containing triplexes were similar in their enhanced stabilities at pH 6.1 and, amongst the four triplexes, the 2'-O-methyl was the most stable at pH 5.0. Furthermore, an experiment using a 34-mer duplex DNA suggested that the 2'-O methyl RNA-triplex was destabilized, mostly as a result of the incorporation of a mismatched triplet, as compared to the DNA triplex counterpart. Thus, 2'-O-methyl RNA can serve as an effective probe for duplex DNA. PMID- 1633848 TI - Primary structure of three minor isoforms of amphioxus sarcoplasmic calcium binding proteins. AB - Previously we reported the amino acid sequences of 4 well-defined sacroplasmic, high-affinity Ca(2+)-binding proteins in the protochordate amphioxus, Branchiostoma lanceolatum [1]. Here we report on the complete amino acid sequence determination of 3 additional minor isoforms. The seven isoforms differ from each other in 9 positions of a contiguous 17-residue-long segment (positions 20-36) and can be classified in a alpha (ASCP I, III and IV) and a beta lineage (ASCP II, V, VI and VII). PMID- 1633849 TI - Functional expression of a plant plasma membrane transporter in Xenopus oocytes. AB - A full-length cDNA clone for the H+/hexose co-transporter (STP1) from Arabidopsis thaliana has been transcribed in vitro and the mRNA injected into Xenopus oocytes. Under optimized conditions, oocytes injected with the STP1 mRNA accumulated 3-O-[methyl-14C]glucose at rates of more than a 1000-fold greater than water-injected control oocytes. A hexose-elicited depolarization of the oocyte membrane potential was demonstrated, and uptake was shown to be stimulated by low external pH, confirming the activity of a H+/hexose co-transport system. This is the first example of the functional expression of a plant membrane transporter in oocytes. PMID- 1633850 TI - Protein deamidase from germinating wheat grains. AB - A new enzyme catalyzing the deamidation of seed storage proteins was found in germinating wheat grains and was partially purified. It also acts on egg lysozyme, horse hemoglobin and reduced RNAse, glutamine and Gly-L-Gln-L-Tyr. No activity was observed when using ovalbumin, serum albumin, RNAse, insulin, asparagine and an asparagine-containing peptide. Only glutaminyl residues appear to be deamidated by this enzyme. It differs from transglutaminase and proved to be a true protein deamidase. PMID- 1633851 TI - Fluorescence study of the nucleic acid binding site of vimentin. AB - A selective tyrosine fluorescence quenching is found on interaction of vimentin with poly(dT) and poly(rA). However, addition of poly(dA) does not result in tyrosine quenching. The number of nucleotides covered by vimentin upon binding (n) of poly(dT) (50 +/- 4) appeared to be approximately the same as for poly(rA) (44 +/- 4), while the apparent binding constant (K(app)) of the latter is slightly larger (5.0 +/- 2.0 x 10(7) M-1.cm-1 vs. 2.5 +/- 0.5 x 10(7) M-1.cm-1). The finding that there exists a specific strong interaction between vimentin and nucleic acids could help in the search for cellular functions of intermediate filament proteins. PMID- 1633852 TI - The application of 1H NMR chemical shift calculations to diastereotopic groups in proteins. AB - We have calculated chemical shifts for a range of diastereotopic protons in proteins (i.e. methylene protons, and the methyl groups of valine and leucine residues), using a recently optimised method for chemical shift calculation. The calculations are based on crystal structure coordinates, and have been compared with experimental stereospecific assignments. The results indicate that chemical shifts can be used to suggest stereospecific assignments with about 80% probability of being correct, in cases where both the experimental and the calculated chemical shift differences between a pair of diastereotopic protons are greater than 0.3 ppm. Inaccurate calculations are shown to be caused in most cases by differences between crystal and solution structures. Furthermore, chemical shift calculations based on NMR structures are shown to be capable of acting as a further constraint on structure, by limiting the range of side-chain conformations adopted in structures calculated from NMR data. PMID- 1633853 TI - Intranuclear topological distribution of HIV-1 trans-activators. AB - Subcellular localization of human immunodeficiency virus type I (HIV-1) Tat and Rev was examined using a confocal laser scanning microscope (CLSM). In transfected COS-7 cells, Tat resided exclusively in the perinocleolar region, while Rev infiltrated fully into the nucleoli. The chimeric Tat in which the nucleolar targeting signal was replaced by that of Rev, which retains trans acting activity of Tat, remained still in the perinucleolar region as wild-type Tat. Perinucleolar distribution of Tat protein suggests the existence of a novel nucleolar architecture that affects transcription. PMID- 1633854 TI - Thermoregulatory, carboxyatractylate-sensitive uncoupling in heart and skeletal muscle mitochondria of the ground squirrel correlates with the level of free fatty acids. AB - Thermoregulatory uncoupling of oxidative phosphorylation has been studied in heart and skeletal muscle mitochondria of ground squirrels. The respiratory rate of mitochondria in the presence of oligomycin was found to be much higher in winter (in hibernating, arousing, or aroused animals) than in summer. This additional respiration is strongly (arousing animals) or completely (hibernating and aroused animals) inhibited by carboxyatractylate (CAtr) and bovine serum albumin (BSA). The CAtr- and BSA-induced decreases in the rate of respiration are accompanied by membrane potential increases. The rate of the CAtr- and BSA sensitive respiration is proportional to the content of free fatty acids which, in the heart, decreases in the order: arousing greater than aroused = hibernating greater than summer animals. Maximal respiratory rates observed in the presence of dinitrophenol (arousing greater than aroused greater than summer greater than hibernating animals) do not parallel the fatty acid level. It is assumed that some heat production in the winter animals is due to fatty acid-induced, ATP/ADP antiporter-mediated uncoupling in heart and skeletal muscle mitochondria. The peak of heat production during arousal after hibernation also includes some other stimulatory effect on mitochondrial respiration. PMID- 1633855 TI - Identification of the polypeptides of the major light-harvesting complex of photosystem II (LHCII) with their genes in tomato. AB - Using an improved SDS-PAGE system, the polypeptides of the major chlorophyll a/b light-harvesting complex of PSII (LHCII) from tomato leaves were resolved into five polypeptide bands. All the polypeptides were matched with the genes encoding them by comparing amino acid sequences of tryptic peptides with gene sequences. The two major LHCII bands (usually comigrating as a '27 kDa' polypeptide) were encoded by cab1 and cab3 (Type I LHCII) genes. A third strong band of about 25 kDa was encoded by cab4 (Type II) genes. Polypeptides from two minor bands of 23 24 kDa were not N-terminally blocked; their N-terminal sequences showed they were Type III LHCII proteins. One complete cDNA clone and several incomplete clones for Type III polypeptides were sequenced. Combined with the peptide sequences, the results indicate that there are at least four different Type III genes in tomato, encoding four almost identical polypeptides. Thus, all the LHCII CAB polypeptides have been identified, and each type of LHCII polypeptide is encoded by distinct gene or genes in tomato. PMID- 1633856 TI - Primary structure and functional expression of a choline transporter expressed in the rat nervous system. AB - Synthesis of the neurotransmitter acetylcholine in cholinergic nerve terminals is regulated by a sodium-driven high-affinity choline uptake system in the plasma membrane. We have isolated cDNAs from rat spinal cord and brainstem which encode a choline transporter (CHOT1). The predicted protein shares considerable amino acid identity and several structural features including twelve putative transmembrane regions with other neurotransmitter transporters. Expression of in vitro transcribed CHOT1 RNA in Xenopus oocytes generated Na(+)-dependent choline uptake, which was not seen in control oocytes. Amplification by polymerase chain reaction (PCR) revealed significant amounts of CHOT1 mRNA in brain, cerebellum, spinal cord and, to a lesser extent, heart, but only very low expression in lung, kidney and muscle. PMID- 1633857 TI - Caf1R gene and its role in the regulation of capsule formation of Y. pestis. AB - A new transcription unit of the f1 gene cluster was found. The DNA sequencing revealed one long open reading frame. Deletion and frame shift mutation analyses have demonstrated the importance of a corresponding gene product for the F1 antigen biosynthesis. A homology of the deduced amino acid sequence with that of AraC family DNA-binding regulators was shown. A potential regulatory DNA region is discussed. PMID- 1633858 TI - Structure and expression of Xenopus prohormone convertase PC2. AB - The multifunctional prohormone, proopiomelanocortin (POMC), is processed in the melanotrope cells of the pituitary pars intermedia at pairs of basic amino acid residues to give a number of peptides, including alpha-melanophore-stimulating hormone (alpha-MSH). This hormone causes skin darkening in amphibians during background adaptation. Here we report the complete structure of Xenopus laevis prohormone convertase PC2, the enzyme thought to be responsible for processing of POMC to alpha-MSH. A comparative structural analysis revealed an overall amino acid sequence identity of 85-87% between Xenopus PC2 and its mammalian counterparts, with the lowest degree of identity in the signal peptide sequence (28-36%) and the region amino-terminal to the catalytic domain (59-60%). The occurrence of a second, structurally different PC2 protein reflects the expression of two Xenopus PC2 genes. The expression pattern of PC2 in the Xenopus pituitary gland of black- and white-adapted animals was found to be similar to that of POMC, namely high expression in active melanotrope cells of black animals. This observation is in line with a physiological role for PC2 in processing POMC to alpha-MSH. PMID- 1633859 TI - A molecular model for the tumour-associated antigen, p97, suggests a Zn-binding function. AB - The primary structure of p97 (melanotransferrin) has been compared with other members of the transferrin superfamily. A molecular structure of p97 has been modelled based on the crystal structure of diferric rabbit serum transferrin. The most significant amino acid substitutions in p97 are almost exclusively limited to only two regions; the C-lobe iron-binding cleft and the interlobe contact region. The latter includes within the N-terminal lobe a Zn-binding consensus sequence found in metallopeptidases, and in the C-terminal lobe a glutamic acid residue (Glu-394) capable of completing a potential thermolysin-like Zn-binding site. Thus, p97 may have a Zn-binding potential, unique amongst the transferrin superfamily. PMID- 1633860 TI - Time-resolved fluorometry of purple membrane of Halobacterium halobium. O640 and an O-like red-shifted intermediate Q. AB - The photocycle of the light-adapted purple membrane was studied with a time resolved fluorometry apparatus: fluorescence of the sample suspension (greater than 660 nm) was pumped with a 633-nm cw laser and the temporal change induced by a 532-nm pulsed laser was measured with a photon-counting-type transient recorder. The formation and the decay of the O640 intermediate were clearly observed in the pH region between 4.0 and 11.4. A photochemical cycle of N560 was apparently driven in alkaline suspension (pH greater than 9.3). An O-like fluorescent intermediate Q appears and decays with time constants of less than 0.1 ms and 1.7 +/- 0.2 ms, respectively. PMID- 1633861 TI - The polyoxyethylene/polyoxypropylene block co-polymer poloxamer-407 selectively redirects intravenously injected microspheres to sinusoidal endothelial cells of rabbit bone marrow. AB - Small colloidal particulates (150 nm and below, in diameter) can be redirected specifically to the rabbit bone marrow following intravenous administration by coating their surface with the block co-polymer poloxamer-407, a non-ionic surfactant. The coated colloids are sequestered by the sinusoidal endothelial cells of the bone marrow and are accumulated in dense bodies within these cells. The uptake of poloxamer-407-coated colloids by marrow endothelial cells suggests that the steric repulsive barrier, imposed by the polyoxyethylene segment of the polymer, to particle-cell interaction can apparently be overcome by a specific interaction mechanism(s) with the cell surface. Such a dramatic uptake cannot be achieved with other block co-polymers of similar structure to poloxamer-407. The application of the current model for the site-specific targeting of drug carriers to bone marrow and the prevention of the adherence of metastases of tumours which selectively colonize the bone marrow endothelium is discussed. PMID- 1633862 TI - Transcripts of the viroid central conserved region contain the local tertiary structural element found in full-length viroid. AB - The viroid central conserved region (CCR) is highly conserved among different viroids and is thought to be involved in viroid replication. A novel tertiary structure occurs in the CCR of native circular potato spindle tuber RNAs. To permit more detailed studies of this structural element, a small RNA oligonucleotide containing the CCR of the viroid genome was synthesized. The tertiary structure of these CCR transcripts was examined by UV-crosslinking of the RNA, followed by mapping of the crosslink using limited alkaline digestion and classical RNA secondary analysis. The CCR transcript was found to undergo UV crosslinking between the same two bases as in full-length viroid, indicating that the tertiary structure is the same and that the CCR transcript will be useful for the affinity purification of host components. PMID- 1633863 TI - A functional tomato ACC synthase expressed in Escherichia coli demonstrates suicidal inactivation by its substrate S-adenosylmethionine. AB - 1-Aminocyclopropane-1-carboxylate (ACC) synthase is a key enzyme in the biosynthesis of the plant hormone, ethylene. We have isolated, sequenced and expressed a functional tomato (cv Pik-Red) ACC synthase gene in Escherichia coli. ACC synthase expressed in E. coli was inactivated by incubation with S adenosylmethionine (SAM), the half-time of which was concentration dependent. Mixing the tomato fruit protein extract with the cell-free extract from transformed E. coli did not affect SAM-dependent inactivation of ACC synthase activity. Thus, single isoforms of the ACC synthase enzyme, which demonstrate the biochemical features expected of the tomato fruit enzyme, can be expressed in E. coli and their structure-function relationships investigated. PMID- 1633864 TI - A rapid-kinetic study of the class C beta-lactamase of Enterobacter cloacae 908R. AB - The individual rate constants for acylation and deacylation (k2 and k3, respectively) of the class C beta-lactamase of Enterobacter cloacae 908R by ampicillin and carbenicillin have been determined. For several other beta lactams, the value of k2 was too high to be determined and the k2/k3 ratio could be larger than 10,000. Branched pathways were also shown to occur with several penicillins and cephalosporins. PMID- 1633865 TI - Crystal structure of Pseudomonas aeruginosa apo-azurin at 1.85 A resolution. AB - The 3D structure of apo-azurin from Pseudomonas aeruginosa has been determined at 1.85 A resolution. The crystal structure is composed of two different molecular forms of apo-azurin arranged as hetero-dimers in the tetramer of the asymmetric unit. Form 1 closely resembles the holo-protein lacking copper. Form 2 shows differences in the metal binding site region induced by the incorporation of a solvent molecule into this site. The positions of the copper ligands His46 and His117 are shifted by 0.6 A and 1.6 A. The His117 side chain adopts a position at the surface of the protein, thereby facilitating access to the copper site. The presence of two different molecular forms of apo-azurin in the crystal lattice may reflect an equilibrium between the two forms in solution. 1H-NMR spectra of apo-azurin recorded as a function of pH show that at high pH the line broadening of His35, His46 and His117 resonances is consistent with an interconversion between forms 1 and 2. At low pH, no broadening is observed. This may indicate that here the interconversion is fast on the NMR timescale. PMID- 1633867 TI - On the functional role of the Tyr-639 residue of bacteriophage T7 RNA polymerase. AB - Substitution of Asp for a Tyr residue normally present at position 639 of the bacteriophage T7 RNA polymerase leads to a drastic drop in the enzymatic activity. This mutation does not affect the enzyme-promoter interaction but decreases the ability of the RNA polymerase to discriminate between GTP and ATP molecules, resulting in a decrease in the rate of the incorporation of the nucleotide into the RNA chain. PMID- 1633866 TI - Photogeneration of NADH under coupled action of CdS semiconductor and hydrogenase from Alcaligenes eutrophus without exogenous mediators. AB - Photoreduction of NAD has been accomplished by a system consisting of the NAD dependent hydrogenase from Alcaligenes eutrophus immobilized on CdS particles with formate as artificial electron donor. Enzymatically active NADH is formed under illumination of this system by visible light. Accumulation of the coenzyme dimer (NAD)2 was not detected. NAD photoreduction is supposed to proceed via the direct electron transfer from the semiconductor to the enzyme electron transport chain. However, NADH formation as a result of hydrogenase interaction with anion radicals (CO2.-) formed in the course of formate photooxidation cannot at present be excluded. PMID- 1633868 TI - Evidence for the tetraplex structure of the d(GT)n repetitive sequences in solution. AB - The ability of oligonucleotides 3'-d(GT)5pO(CH2)6Opd(GT)5-5' (anti[d(GT)]) and 3' d(GT)5pO(CH2)6Opd(GT)5-3' (par[par[d(GT)]) to form tertiary structures has been studied. Circular dichroism (CD) as well as the fluorescence of the ethidium bromide (EtBr) complexes with oligonucleotides and hydrodynamic volume measurements in solutions containing 0.01 M phosphate buffer, pH 7 and NaCl in concentrations from 0.1 M to 1 M, have been used. The data obtained in the temperature interval from 3 degrees C to 10 degrees C are in good agreement with the structure suggested earlier where the par[d(GT)] and anti[d(GT)] form structures with four parallel strands in which layers of four G-residues alternate with unpaired bulged-out T-residues. Ethidium bromide interacts with the structure in a cooperative manner. Two ethidium bromide molecules intercalate between two layers of four G-residues. PMID- 1633869 TI - Transmembrane electron transport in ascorbate-loaded plasma membrane vesicles from higher plants involves a b-type cytochrome. AB - The possible involvement of a high-potential b-type cytochrome in plasma membrane electron transport was tested using ascorbate-loaded membrane vesicles. Absorption spectra demonstrated that the cytochrome was about 89% reduced in these preparations. Use of ascorbate oxidase and washing of the vesicles further indicated that reduction was mediated by intra-vesicular ascorbate. Addition of low concentrations of ferricyanide caused a rapid cytochrome oxidation followed by a slower re-reduction. The kinetics of this response indicate that the electron acceptor was fully reduced before re-reduction of the cytochrome occurred. These observations suggest that the b-type cytochrome mediates transmembrane electron transfer. PMID- 1633870 TI - Generation of Gla-domainless FVIIa by cathepsin G-mediated cleavage. AB - Coagulation factor VII contains ten gamma-carboxyglutamic acid residues in the N terminal region (Gla-domain) which are essential for the hemostatic function of FVII. The present study shows that granulocyte cathepsin G degrades the Gla domain of FVIIa in vitro. Characterization of the truncated FVIIa by SDS-PAGE and N-terminal amino acid sequence analysis revealed that cleavage had occurred between Tyr-44 and Ser-45 and that further cleavage was only obtained on extensive cathepsin G exposure. Cleavage of vitamin K-dependent coagulation factors by cathepsin G may play a role in vivo, and it offers a convenient way of obtaining proteins deprived of their Gla-domain for functional and structural studies. PMID- 1633871 TI - Induction of thromboxane synthase and prostaglandin endoperoxide synthase mRNAs in human erythroleukemia cells by phorbol ester. AB - The effects of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the mRNA levels of two enzymes, thromboxane synthase (TXS) and prostaglandin endoperoxide synthase (PES), responsible for the synthesis of thromboxane A2 from arachidonic acid, were studied in human erythroleukemia (HEL) cells by RNA blot analysis. TPA induced both TXS and PES mRNAs in HEL cells in a dose-dependent manner at 36 h. The half-maximal and maximal effects for the induction of both mRNAs were at approximately 3 x 10(-9) M and at 10(-8) M, respectively. TXS and PES mRNA levels increased in a time-dependent fashion by TPA, and reached to 7- and 3.5-fold of the control, respectively after 48 h of TPA treatment. These results suggest that expression of TXS and PES genes in HEL cells were simultaneously stimulated by TPA. PMID- 1633872 TI - Expression of c-fos, c-jun, jun-B, metallothionein and metalloproteinase genes in human chondrocyte. AB - Normal and osteoarthritic (OA) human articular cartilage chondrocytes, released enzymatically in the presence of 0.5% fetal calf serum, display constitutive expression of early response activating protein (AP-1) genes; c-fos, c-jun and jun-B. Among the late AP-1 responsive genes, total metallothionein (MT) and stromelysin mRNAs were expressed at high levels in both normal and OA chondrocytes, while collagenase and hMT-IIA mRNA levels were elevated only in OA individuals. Despite the common AP-1 sequences present in their promoter regions, the three late genes were differentially expressed. PMID- 1633873 TI - Ca2+/calmodulin is involved in growth factor-induced retinoblastoma gene product phosphorylation in human vascular endothelial cells. AB - In human vascular endothelial cells, both growth factor-induced DNA synthesis and retinoblastoma gene product (RB) phosphorylation are absolutely dependent on extracellular Ca2+, and are potently inhibited by an active calmodulin antagonist, W-7, but not an inactive analogue, W-12. A reduction in the extracellular Ca2+ or an addition of W-7 as late as 8 h after growth factor stimulation still inhibits both RB phosphorylation and DNA synthesis to the full extent. However, once RB phosphorylation occurs 12-16 h after addition of the growth factors, it is not reversed by subsequent Ca2+ reduction or W-7. These results suggest the existence of a Ca2+/calmodulin-dependent process relatively late in the mitogenic signalling cascade, at a step proximal to RB phosphorylation reaction itself. PMID- 1633874 TI - Molecular cloning of a novel ras-like protein from chicken. AB - We have isolated a cDNA clone from a chicken DNA expression library which codes for a ras-like polypeptide of 216 amino acid residues. This polypeptide is closely related to the human protein TC4 and to the yeast protein Spil, two novel proteins that may be involved in the coordination of the cell cycle. In the amino terminal region, the three polypeptides possess a P-loop motif characteristic of GTP-binding proteins. At the carboxy-terminal end, however, they lack the typical CAAX-box which is usually responsible for membrane anchorage of ras-like proteins. It is therefore likely that the three polypeptides define a new subclass of GTP-binding proteins within the ras-like superfamily. PMID- 1633875 TI - Crystal and molecular structure of RNase Rh, a new class of microbial ribonuclease from Rhizopus niveus. AB - The crystal structure of RNase Rh, a new class of microbial ribonuclease from Rhizopus niveus, has been determined at 2.5 A resolution by the multiple isomorphous replacement method. The crystal structure was refined by simulated annealing with molecular dynamics. The current crystallographic R-factor is 0.200 in the 10-2.5 A resolution range. The molecular structure which is completely different from the known structures of RNase A and RNase T1 consists of six alpha helices and seven beta-strands, belonging to the alpha+beta type structure. Two histidine and one glutamic acid residues which were predicted as the most probably functional residues by chemical modification studies are found to be clustered. The steric nature of the active site taken together with the relevant site-directed mutagenesis experiments (Irie et al.) indicates that: (i) the two histidine residues are the general acid and base; and (ii) an aspartic acid residue plays a role of recognizing adenine moiety of the substrate. PMID- 1633876 TI - Age and sex influence expression of plasmid DNA directly injected into mouse skeletal muscle. AB - Direct injection of plasmid DNA into the skeletal muscle has been proposed as a means of effecting somatic gene therapy. We examined the influence of age and sex on the level of expression of an SV40-CAT construct injected into mouse muscle. Age markedly affected expression, with peak values in the 4-6 week age class which were significantly higher than in animals older than 10 weeks. Sex also altered expression, with higher levels of CAT activity seen in males compared to females. We conclude that the rate of growth is important in determining levels of expression of directly injected DNA. PMID- 1633877 TI - Identification of a novel transthyretin variant (Val30----Leu) associated with familial amyloidotic polyneuropathy. AB - A novel variant transthyretin which contains a leucine-for-valine substitution at position 30 was isolated and identified in the serum of a patient with familial amyloidotic polyneuropathy (FAP). The amino acid substitution was proven to result from a guanine-to-cytosine change at the first base of codon 30 located in exon 2 in the mutated transthyretin gene by restriction fragment length analysis on the amplified transthyretin gene using Cfr13 I. The study indicates that the point mutation of the transthyretin gene is a cause of the disorder. PMID- 1633878 TI - Independence of the carotene and sterol pathways of Phycomyces. AB - Light, chemicals, and mutations that affect the carotene content of the fungus Phycomyces blakesleeanus had practically no effect on the ergosterol content. Lovastatin, a specific inhibitor of hydroxymethylglutaryl coenzyme A reductase, blocked growth at 1 microM; sodium DL-mevalonate (10 mM) fully reversed this inhibition. In the presence of [14C]mevalonate, a carS mutant accumulated 16 times more beta-carotene than the wild-type with a specific radioactivity five times lower. The specific radioactivity of ergosterol was different from that of beta-carotene, even when calculated in terms of the constituent isoprene units, and unaffected by the carS mutation. The carotene and sterol pathways of Phycomyces are independently regulated and physically separated in different subcellular compartments. PMID- 1633879 TI - Loss of transcriptional repression contributes to the ectopic expression of the calcitonin/alpha-CGRP gene in a human lung carcinoma cell line. AB - The calcitonin/alpha-CGRP (CT/CGRP) gene is ectopically expressed in a wide variety of neoplasia. We have investigated the molecular mechanisms responsible for this ectopic expression in the human cell line BEN, which is derived from a poorly differentiated squamous cell lung carcinoma. We show that a trans-acting factor which represses expression of the CT/CGRP gene in HeLa cells is absent or inactive in BEN cells, and have localised the repressor binding site to a 53 bp fragment 1500 bp upstream of the transcription start site. PMID- 1633880 TI - Di-myo-inositol-1,1'-phosphate: a new inositol phosphate isolated from Pyrococcus woesei. AB - A new inositol derivative could be isolated from the Archaeum Pyrococcus woesei and identified as di-myo-inositol-1,1'-phosphate by 1H, 31P NMR spectroscopy, mass spectrometry and thin layer chromatography. In P. woesei, this inositol phosphate represents the dominant counterion of K+ which ranges from 500 to 600 mM. The role of the potassium salt of di-myo-inositol-1,1'-phosphate as thermostabilizer is discussed. PMID- 1633881 TI - Stabilization of basic fibroblast growth factor with dextran sulfate. AB - Dextran sulfate protected bFGF from heat and acid inactivation and from proteolytic degradation. The protective effect was stronger than that of heparin which is known as a stabilizer of bFGF. Dextran sulfate and bFGF formed a high molecular weight complex via ionic interaction when mixed together in aqueous solution. The complex was dissociated when the ionic strength was increased and the protective effect was completely abolished. Successive digestion of bFGF with Staphylococcus aureus V8 protease and pepsin followed by affinity chromatography on an immobilized dextran sulfate column and reversed-phase high performance liquid chromatography yielded three positively charged fragment peptides, Tyr24 Phe30, Tyr106-Trp114 and Tyr124-Leu138. These results suggest that dextran sulfate stabilizes bFGF by binding close to the putative heparin binding sites of the bFGF molecule. PMID- 1633882 TI - Fast and slow kinetics of porin channels from Escherichia coli reconstituted into giant liposomes and studied by patch-clamp. AB - E. coli porins (OmpF and OmpC) were purified and reconstituted into liposomes which were enlarged to giant proteoliposomes by dehydration-rehydration and studied by patch-clamp. The porins could be closed by voltage pulses under -100 mV. The kinetics of closure was slow, with closure events of about 200 pS in 0.1 M KCl. Rapid fluctuations (in the millisecond range) of about one third (60-70 pS) of the large closure steps were also observed. The data are interpreted as follows: an increase in membrane potential favours the cooperation transition of multimers towards an inactivated state, while monomers which have not been inactivated can flicker rapidly between an open and a short-lived closed state. PMID- 1633883 TI - Construction and functional analysis of hybrid interleukin-6 variants. Characterization of the role of the C-terminus for species specificity. AB - We have constructed several hybrid human interleukin-6 (IL-6) variants in which the carboxyl-terminus, which includes a receptor binding site of IL-6 has been replaced with the C-terminus of various proteins homologous to human IL-6. IL-6 hybrids with the C-terminus of human growth hormone and human granulocyte-colony stimulating factor maintain part of the biological activity of human IL-6. Replacing the C-terminus of human IL-6 with the C-terminus of mouse and rat IL-6 resulted in a normal or increased activity on a mouse cell line; however, this gave a low (to 200-fold less) activity on a human cell line compared to wild-type human IL-6. We therefore conclude that the C-terminus of IL-6 plays an important role in the species specificity of IL-6. PMID- 1633884 TI - Two different Ca2+ ion binding sites in factor VIIa and in des(1-38) factor VIIa. AB - The Ca2+ ion binding of factor VIIa and the derivative lacking the gamma carboxyglutamic acid domain, des(1-38) factor VIIa, was investigated using intrinsic protein fluorescence and Tb3+ ion phosphorescence methods. Binding of Ca2+ ions giving rise to a decrease in the intrinsic protein fluorescence (approximately 50% at saturating conditions) is seen with both proteins. Each of the saturation curves is in accordance with the formation of a 1:1 complex of factor VIIa-Ca2+ (KD approximately 30 microM) and des(1-38) factor VIIa-Ca2+ (KD approximately 40 microM)). Yet another Ca2+ ion binding site reveals itself in each protein in Tb3+ ion phosphorescence experiments. Ca2+ ion competition studies have showed 1:1 complexes (KD's approximately 2 mM). The results are interpreted in terms of two different Ca2+ ion binding sites, one in the EGF-1 domain and one in the Gly-209-Gln-221 loop of the serine proteinase part. PMID- 1633885 TI - Regeneration of vitamin E in rat polymorphonuclear leucocytes. AB - The objectives of this study were to determine whether the recycling of tocopherol occurs in elicited rat polymorphonuclear leukocytes and if so, whether the recycling process is enzymic or chemical. When incubated with hemoglobin, tocopherol was oxidized in cell homogenates in a time- and concentration dependent manner. The oxidized tocopherol could be regenerated by addition of ascorbate, glutathione or nordihydroguaiaretic acid. Time course studies showed a rapid regeneration of tocopherol which peaked at 1 min after the addition of reductants. Determination of the regeneration reaction in the presence of CHCl3 and MeOH indicated that under these enzyme-denaturing conditions, a considerable amount of tocopherol was still regenerated, suggesting that the regeneration reaction is predominantly a chemical reaction. This study provided direct evidence from mass analysis that oxidized vitamin E can be regenerated by cellular water-soluble reductants such as ascorbate and glutathione. PMID- 1633886 TI - Carbon-by-carbon discrimination of 13C incorporation into liver fatty acids. AB - Quantitative carbon-by-carbon analysis would be useful in determining the origin and fate of carbons involved in fatty acid metabolism. Incorporation of 13C from 2-[13C]acetate into specific carbons of liver fatty acids was lowest at the n-2 carbon of saturates and monoenes but was 47% greater at acyl C1 than at C2, suggesting substantial redistribution of the 13C from C2 to C1 of acetyl CoA or malonyl CoA prior to 13C incorporation into fatty acids during de novo synthesis or during elongation. Thus, 13C derived from exogenous acetate can be quantitatively measured and is differentially incorporated into individual carbons depending on position in the fatty acid molecule. PMID- 1633887 TI - On the activation-inactivation coupling in Shaker potassium channels. AB - The 'ball-and-chain' model suggests the existence of a negative site which may attract the positively charged inactivation ball to occlude the pore when the channel is in the open state. For Shaker K+ channels, we propose that the state dependent negative site be tryptophan-435, which becomes negatively charged after receiving an electron from tyrosine-445. The kinetic scheme for the channel's activation-inactivation coupling as derived from the YW-gated model resembles a successful 'scheme 8' proposed by Zagotta and Aldrich. Our model suggests that the final rapid voltage-independent transition to the open state is due to the deprotonation of tyrosine-445. PMID- 1633888 TI - Barley (1----3,1----4)-beta-glucanase isoenzyme EI gene expression is mediated by auxin and gibberellic acid. AB - Treatment of young barley leaves with indole acetic acid (IAA) or gibberellic acid (GA3) results in a dramatic increase in levels of (1----3,1----4)-beta glucanase isoenzyme EI transcripts. In young roots of comparable age, levels of isoenzyme EI mRNA are high; IAA inhibits expression while GA3 has no effect on mRNA levels. The addition of both abscisic acid and GA3 to leaves, roots and aleurone layers leads to higher levels of (1----3,1----4)-beta-glucanase isoenzyme EI mRNA than is found with Ga3 alone. Little or no expression of (1--- 3,1----4)-beta-glucanase isoenzyme EII is detected in vegetative tissues, but in isolated aleurone layers GA3 enhances levels of isoenzyme EII transcripts, as does IAA. Thus, the two barley (1----3,1----4)-beta-glucanase genes respond quite differently to phytohormone treatment, depending on the tissue and its stage of development. PMID- 1633890 TI - Immunology and endometriosis. PMID- 1633889 TI - Ovarian hyperstimulation syndrome in novel reproductive technologies: prevention and treatment. AB - OBJECTIVE: To overview the world literature on ovarian hyperstimulation syndrome (OHSS) and modes of prevention and treatment of OHSS. STUDY SELECTION: All the pertinent literature on OHSS, its prevention, and strategies for treatment were reviewed. PREVENTION: Key to prevention is proper identification of the population at risk, which includes women with either the hormonal or the morphological signs of polycystic ovarian disease, high serum estradiol (E2) before human chorionic gonadotropin (hCG) administration (E2 greater than 4,000 pg/mL), multiple follicular response (greater than 35), younger age, and lean habitus. When a high risk situation is recognized, ovulatory dose of hCG may be reduced, avoided (with cycle cancellation), or substituted by gonadotropin releasing hormone or its agonist. Luteal support with hCG is to be bypassed. To minimize risk of OHSS, endogenous pregnancy-drived hCG may be eluded by judicious cryopreservation of all embryos. Last, follicular aspiration will allow higher levels of E2 and larger number of follicles to be matured with lesser risk of OHSS than conventional ovulation induction without follicular aspiration. TREATMENT: In-house for the severe and intensive care for the critical form. Meticulous fluid and electrolyte balance using both crystalloids and colloids (albumin) until hemoconcentration abates. Paracentesis is indicated for tight ascites, deteriorating kidney functions, and symptomatic relief. Diuretics may be prudently used once hemodilution is achieved. Dopamine drip may be used as a renal rescue, whereas heparin is indicated for thromboembolic phenomena and surgery reserved for abdominal catastrophies. Therapeutic interruption of an early gestation may be lifesaving when all other measures have failed. CONCLUSIONS: Although severe and critical OHSS may not be completely avoided, early recognition of high-risk factors, judicious prevention schemes, and treatment strategies should reduce the complication and long-term sequelae of this iatrogenic syndrome. PMID- 1633891 TI - Menstrual cyclicity of CA-125 in patients with endometriosis. AB - OBJECTIVE: To examine the serum levels of CA-125 in the menstrual, follicular, and luteal phases of the menstrual cycle in women with endometriosis and to determine if serum CA-125 levels drawn during menses improve the clinical utility of the test in diagnosing endometriosis. DESIGN: Serum CA-125 was measured in the menstrual, follicular, and luteal phases of the cycle preceding surgery. CA-125 levels for each phase were categorized by postoperative diagnosis and endometriosis stage. SETTING: The reproductive endocrine unit of a tertiary care university-affiliated hospital. PATIENTS: A total of 65 patients were recruited from the Fertility and Endocrine Unit and the Gynecology Service of Brigham and Women's Hospital. MAIN OUTCOME MEASURE: Serum CA-125 levels were measured by an immunoradiometric assay and were stratified by menstrual cycle phase, diagnosis, and stage of endometriosis. The menstrual cycle phase was confirmed by serum estradiol and progesterone measurements. RESULTS: Serum CA-125 levels in patients with stages II to IV endometriosis were significantly elevated in the menstrual phase compared with levels drawn in the nonmenstrual follicular and luteal phases. The sensitivity and specificity of CA-125 for the diagnosis of endometriosis were not significantly better in the menstrual than in the follicular or luteal phases. CONCLUSIONS: Despite menstrual cyclicity of CA-125, measurement of serum CA-125 during menses does not improve the clinical utility of the test in the diagnosis of endometriosis. PMID- 1633893 TI - The natural killer activity of peritoneal fluid lymphocytes is decreased in women with endometriosis. AB - OBJECTIVE: To investigate the local natural killer (NK) activity of the peritoneal fluid mononuclear cells (PFMC). DESIGN PATIENTS: In a prospective way, the NK activity (K562-assay) was measured in peripheral blood (PB) and peritoneal fluid (PF) of 44 women who underwent a laparoscopy for infertility and/or pain at the University Hospital of Gasthuisberg, Leuven, Belgium. MAIN OUTCOME MEASURE: The NK activity of peripheral blood mononuclear cells and PFMC, the number and concentration of PFMC, the percentage of lymphocytes versus macrophages by May Grunwald-Giemsa staining and the estradiol and progesterone concentration of the PF were correlated together and with the severity of endometriosis. RESULTS: We demonstrated that there is a significant NK activity in PF and that this activity is decreased in women with endometriosis. This defect was more pronounced in the follicular phase of the cycle compared with the postovulatory phase. In PB of the same 44 women, the decreased NK activity correlated with the severity of the disease. This confirms our previous report on another 34 women. CONCLUSIONS: The NK activity is decreased in women with endometriosis and correlated significantly with the severity of the disease in both the PB and PF of women with endometriosis. PMID- 1633892 TI - Glucocorticoid treatment decreases sera embryotoxicity in endometriosis patients. AB - OBJECTIVE: To investigate the effect of short-term glucocorticoid administration on embryotoxicity of sera from infertile patients with mild to moderate endometriosis. DESIGN: Prospective longitudinal study. SETTING, PATIENTS: Eight infertile patients with mild to moderate endometriosis and a control group of eight infertile patients with tubal infertility were selected on the basis of laparoscopic examination. INTERVENTIONS: Basal (B) serum collection and day 1 (T1), day 3 (T2), day 6 (T3), and day 12 (T4) serum drawn after a 3-day glucocorticoid treatment in endometriosis patients. MAIN OUTCOME MEASURE: Embryotoxicity of endometriosis sera, before and after glucocorticoid treatment, was investigated using a bioassay performed on two-cell mouse embryos. Interleukin 1 alpha (IL-1 alpha) and antismooth muscle, antimitochondrial, and antinuclear autoantibodies were also tested in these sera. RESULTS: At 50% concentration, endometriosis serum is embryotoxic in comparison with control; 0% versus 61% of the embryos reached the blastocyst stage at 72 hours, respectively (basal versus control, P less than 0.001). However, this embryotoxicity significantly decreases 12 days after glucocorticoid treatment in comparison with untreated sera; 32.4% versus 0% of the embryos reached blastocyst stage at 72 hours, respectively (T4 versus basal, P less than 0.001), although they did not reach nontoxic levels (greater than 50%). Interleukin 1 alpha was undetectable in all samples analyzed. In endometriosis sera, antismooth muscle antibody was detected. CONCLUSIONS: At 50% concentration, serum from infertile patients with minimal to moderate endometriosis appears to be embryotoxic to the in vitro development of two-cell mouse embryos. However, this embryotoxicity significantly decreases 12 days after a 3-day treatment with glucocorticoids. PMID- 1633894 TI - Elevated interleukin-6 levels in peritoneal fluid of patients with pelvic pathology. AB - OBJECTIVE: To determine if interleukin 6 (IL-6) is a normal constituent of peritoneal fluid (PF), and if various types of pelvic pathology influence its presence within the PF microenvironment. STUDY DESIGN: Peritoneal fluid from 73 women obtained at the time of laparoscopy was examined for the presence of IL-6 using an IL-6 specific sandwich enzyme-linked immunosorbent assay. Thirty-nine patients had pelvic endometriosis, 17 had nonendometriotic pelvic adhesive disease, and 17 subjects undergoing tubal sterilization without evidence of pelvic pathology served as controls. RESULTS: Immunoreactive IL-6 was observed in the PF of all 73 subjects (range 0.26 to 11.16 ng/mL). The mean concentration of IL-6 was higher in women with nonendometriotic pelvic adhesions as compared with control subjects (1.28 +/- 0.16 versus 0.80 +/- 0.06 ng/mL, P less than 0.03). There was no difference in the mean peritoneal concentrations of IL-6 between women with endometriosis (1.16 +/- 0.28 ng/mL) and controls, P = 0.38. Twenty seven of 73 patients (37%) demonstrated elevated levels (greater than 1.0 ng/mL) of IL-6. Patients with pelvic adhesions were significantly more likely to have elevated concentrations of IL-6 than controls (10/17 [59%] versus 3/17 [18%], P less than 0.02). Alternatively, the percentage of patients with elevated IL-6 concentrations did not differ between patients with endometriosis or controls (14/39 [36%] versus 3/17 [18%], P greater than 0.10). CONCLUSIONS: These findings demonstrate that IL-6 is a normal constituent of PF and that elevated levels are found in many patients with pelvic adhesions. PMID- 1633895 TI - Peripheral plasma met-enkephalin levels in ovulatory and anovulatory human menstrual cycles. AB - OBJECTIVE: To test the hypothesis that met-enkephalin has a role in human ovulation and that plasma levels may differ between ovulatory and anovulatory ovarian cycles. DESIGN: This is a descriptive study comparing levels of plasma met-enkephalin, gonadotropins, and ovarian steroids in 12 ultrasonically confirmed ovulatory cycles and 12 anovulatory cycles. SETTING: The study took place in the infertility clinic of a large teaching hospital receiving primary and tertiary referrals of both private and public sector patients. PATIENTS: All patients (n = 16) had infertility greater than or equal to 3 years and normal findings on previous investigation including evidence of ovulation. INTERVENTIONS: Ovarian cycles were defined using transabdominal ultrasound scanning. Biochemical analyses were by radioimmunoassay. MAIN OUTCOME MEASURES: The differences between plasma met-enkephalin levels in the two groups of cycles were compared. RESULTS: Met-enkephalin levels are significantly higher in ovulatory cycles with a significant peak in the 2 postovulatory days (Duncan's multiple range test; P less than 0.05). CONCLUSION: Human ovulation is associated with cyclic elevation of plasma met-enkephalin. Further studies are required to elucidate causality. PMID- 1633896 TI - Human chorionic gonadotropin stimulation of relaxin secretion by luteinized human granulosa cells. AB - OBJECTIVE: To determine the effect of human chorionic gonadotropin (hCG) on relaxin secretion by long-term cultures of luteinized human granulosa cells (GC). DESIGN: Luteinized human GC were collected from 10 women undergoing in vitro fertilization (IVF) cycles. Luteinized human GC from each woman were plated in replicate wells at 1 x 10(5) cells/well and exposed to medium 199 (GIBCO, Grand Island, NY), medium 199 with 1 IU/mL hCG, and/or medium 199 with 100 IU hCG/mL. Luteinized human GC were maintained for up to 40 days in culture. Spent media were changed every 2 days and assayed for relaxin and progesterone (P) at the conclusion of each experiment. SETTING: Tertiary care center. PATIENTS, PARTICIPANTS: Luteinized human GC were obtained from women undergoing controlled ovarian hyperstimulation for IVF with one of the following regimens: (1) clomiphene citrate with human menopausal gonadotropins (hMG); (2) hMG alone; or (3) hMG with leuprolide acetate. All women were less than 40 years of age, in good health, and were not taking medications other than those used in the ovulation-induction regimen. MAIN OUTCOME MEASURES: Levels of P and relaxin in spent media. RESULTS: Relaxin secretion by luteinized human GC was dependent on hCG stimulation and was detected only after a time lag in culture. After relaxin secretion was detected, it was maintained throughout the culture period (10 to 22 days). Luteinized human GC produced P immediately under both basal and stimulated conditions. Progesterone production continued throughout the culture period with hCG-stimulated cells producing significantly greater P after 4 to 8 days in culture. CONCLUSIONS: Luteinized human GC obtained at the time of oocyte retrieval secrete relaxin in response to hCG stimulation and secrete P under both basal and hCG-stimulated conditions, thereby serving as a model to explore luteal function and control. PMID- 1633897 TI - Prospective study of anticardiolipin antibodies in immunized and untreated women with recurrent spontaneous abortions. AB - OBJECTIVE: To investigate whether active leukocyte immunization increases levels of anticardiolipin antibodies in women with recurrent spontaneous abortions. To assess the impact of anticardiolipin antibodies on pregnancy outcome in these women. DESIGN: Patients who had received various treatments in an ongoing randomized trial were studied prospectively. SETTING: A department of clinical immunology investigating women with recurrent spontaneous abortions from all over Denmark. PATIENTS: Eighty-nine patients with unexplained recurrent spontaneous abortions whose pregnancies had been completed during the course of the trial. INTERVENTIONS: After randomization, 44 patients were actively immunized with husband's or third party leukocytes, and 27 patients received placebo. Eighteen patients received anticoagulation therapy in pregnancy. MAIN OUTCOME MEASURES: Changes in levels of immunoglobulin (Ig)M class and IgG class anticardiolipin antibodies after active immunization. Frequency of new miscarriages in patients who were positive or negative for anticardiolipin antibodies. RESULTS: Neither IgM nor IgG anticardiolipin antibodies changed significantly after active immunization (P greater than 0.2). The interim results of the immunization trial showed a success rate of 68% in the treated group versus 56% in the placebo group (not significantly different). Relative risk of miscarriage in anticardiolipin antibody-positive patients compared with anticardiolipin antibody-negative patients was 1.3 (95% confidence interval 0.7 to 2.2; P = 0.4) in the combined study groups. CONCLUSIONS: Patients eligible for active immunization did not exhibit significant changes in anticardiolipin antibody levels subsequent to the treatment. The treatment did not seem to provide any overall benefit with respect to pregnancy outcome. Prospectively, the risk of miscarriage in patients positive for anticardiolipin antibodies was not significantly increased. PMID- 1633898 TI - Immunohistochemical analysis of estrogen and progesterone receptors in fallopian tubes during ectopic pregnancy. AB - OBJECTIVE: To study decidualization, estrogen receptor (ER), and progesterone receptor (PR) expression in fallopian tubes containing an ectopic pregnancy (EP). DESIGN: Assessment of decidual reaction by light microscopy, staining of ER and PR in epithelium and stroma by immunohistochemical methods. SETTING: Academic hospital. PATIENTS: Twelve women with an ampullary located EP. INTERVENTION: A partial or complete tubal resection. RESULTS: Only minimal decidualization was observed in five tubes. Estrogen receptor expression was noted in glandular cells in seven tubes. No correlation was found between decidualization and ER staining. No PR expression was seen in glandular epithelium or in stroma. CONCLUSIONS: It is postulated that absence of PR is correlated to poor decidualization and to failure of treatment of EP with antiprogestins (RU486). PMID- 1633900 TI - Zygote intrafallopian transfer or in vitro fertilization and embryo transfer for the treatment of male-factor infertility: a prospective randomized trial. AB - OBJECTIVE: To compare zygote intrafallopian transfer (ZIFT) and in vitro fertilization and embryo transfer (IVF-ET) as treatments of male-factor infertility. DESIGN: Patients were prospectively randomized to ZIFT or IVF-ET. SETTING: In vitro fertilization program of the Centre for Reproductive Medicine of the Dutch-speaking Brussels Free University, Belgium, which is a tertiary referral institution. PATIENTS: One hundred fifty-seven couples were enrolled in the study. Inclusion criteria allowed only first trials of couples with long standing infertility caused by a male factor. Female factors were excluded. INTERVENTIONS: In ZIFT, up to three fertilized oocytes were transferred into one single patient fallopian tube by means of laparoscopy 18 hours after insemination. In IVF-ET, cleaving embryos were replaced into the uterine cavity about 48 hours after insemination. MAIN OUTCOME MEASURES: Fertilization and transfer rates, implantation and pregnancy rates, pregnancy outcome, and cost per procedure were evaluated. RESULTS: Implantation rates of 12.3% and 10% per replaced conceptus were achieved for ZIFT and IVF-ET, respectively. CONCLUSIONS: This study demonstrates no therapeutic advantage of ZIFT over IVF-ET in male factor infertility in terms of reproductive outcome or economic benefit. PMID- 1633899 TI - Interruption of endometrial maturation without hormonal changes by an antiprogesterone during the first half of luteal phase of the menstrual cycle: a contraceptive potential. AB - OBJECTIVE: To examine hormonal and endometrial responses to intermittent low-dose RU486 administration in the luteal phase of the menstrual cycle. DESIGN: Prospective open trial in which subjects serve as their own controls. PATIENTS/PARTICIPANTS: Eight normal cycling women. INTERVENTIONS: RU486 (10 mg, orally) was administered 5 and 8 days after urinary luteinizing hormone (LH) surge of treatment cycle. MAIN OUTCOME MEASURES: Daily serum concentrations of LH, follicle-stimulating hormone, estradiol (E2), and progesterone (P) were determined in control, treatment, and recovery cycles (n = 5) or treatment and recovery cycles (n = 3). Changes in endometrial morphology and immunohistochemical staining for P receptor (PR) and E2 receptor (ER) were determined during control (or recovery) and treatment cycles. RESULTS: Cycle length and hormonal patterns were unaltered after treatment with RU486. As demonstrated by reduced stromal edema and delayed glandular development, endometrial dyssynchrony occurred in all eight treatment cycles. In addition, seven of eight treatment cycle endometria demonstrated a decrease in PR staining without consistent change in ER staining. CONCLUSIONS: Two low doses of RU486 given 72 hours apart during the luteal phase of the cycle disrupted ongoing endometrial maturation without altering the hormonal and time course of the menstrual cycle. This study provides a basis for the development of a novel form of luteal contraception. PMID- 1633901 TI - Transvaginal embryo aspiration--a safe method for selective reduction in multiple pregnancies. AB - OBJECTIVE: To evaluate pregnancy outcome after transvaginal selective embryo aspiration and to compare the results with those reported previously with other techniques for selective abortion. DESIGN: Retrospective case series. SETTING: University-based in vitro fertilization (IVF) program. PATIENTS: Nineteen women with multiple pregnancy who conceived after ovulation induction or IVF/gamete intrafallopian transfer. INTERVENTION: Transvaginal ultrasound-guided aspiration of the embryo(s) was performed at 7 to 8 weeks of gestation. MAIN OUTCOME MEASURES: Early and late complications related to the procedure, outcome of pregnancy, and birth weight. RESULTS: In 18 cases, the initial number of embryos (3 to 7) was reduced to two. In 1 case, the number of embryos was reduced from 4 to 3. None of the remaining fetuses vanished after the procedure. One patient delivered at 25 weeks and all other patients delivered healthy, viable infants (a pregnancy loss rate of 5.3%). CONCLUSIONS: Transvaginal embryo aspiration in early gestation appears to be a simple and relatively safe procedure for selective termination in patients with high-order multiple pregnancy. The cumulative loss rate of selective termination procedures previously reported by others is three times higher than the loss encountered in our series. This earlier procedure may be more acceptable to patients from emotional and religious points of view. PMID- 1633902 TI - A prospective randomized study comparing aspiration only with aspiration and flushing for transvaginal ultrasound-directed oocyte recovery. AB - OBJECTIVE: To compare aspiration only with aspiration and flushing of ovarian follicles during transvaginal ultrasound (US)-directed oocyte recovery. DESIGN: Prospective randomized study. PATIENTS: One hundred patients who were undergoing an in vitro fertilization (IVF) treatment cycle. INTERVENTIONS: All patients underwent pituitary desensitization before the administration of gonadotropins. Monitoring of ovarian stimulation and the criteria for the administration of human chorionic gonadotropin were similar in both groups. In patients in whom aspiration alone was used, each follicle was aspirated until it was empty. The US probe was then rotated until every drop of follicular fluid had been aspirated before the next follicle was aspirated and the procedure repeated. For patients who had aspiration and flushing, each follicle was aspirated and then flushed up to a maximum of six times before moving to the next follicle. In both groups, all follicles greater than 10 mm were aspirated. RESULTS: The indication for IVF and mean age of the patients were comparable in the two groups. There were no significant differences between the aspiration and the aspiration and flushing groups in terms of the number of oocytes retrieved (11 versus 9), the oocyte recovery rates (77.5% versus 77.0%), the fertilization rates (55.6% versus 60.0%), the number of embryos transferred (2 versus 2), or the number of clinical pregnancies (12 versus 13). The time taken for oocyte recovery was significantly shorter (15 versus 30 minutes, P less than 0.00001), and the dose of pethidine required significantly less (50 mg versus 100 mg, P less than 0.00001) in the aspiration only group. CONCLUSIONS: Aspiration alone produces comparable oocyte recovery rates as aspiration and flushing while significantly reducing the length of the procedure and the dose of analgesia required. Aspiration alone suffices for virtually all cases during transvaginal US-directed oocyte recovery. PMID- 1633903 TI - Failed oocyte retrieval after lack of human chorionic gonadotropin administration in assisted reproductive technology. AB - OBJECTIVE: To document the absence of oocytes in follicular aspirates in women who, during controlled ovarian stimulation with gonadotropin-releasing hormone agonist (GnRH-a) and menotropins, fail to receive human chorionic gonadotropin (hCG) administration. DESIGN: Retrospective analysis of clinical laboratory data. SETTING: Multicentric. PATIENTS: Five women undergoing controlled ovarian hyperstimulation with GnRH-a and menotropins for programs of assisted reproductive technologies. RESULTS: The documented absence of an hCG injection produced "empty follicles" at transvaginal guided aspiration, despite numerous follicular lavages and aspiration of peritoneal fluid. The lack of oocytes and granulosa-cumulus complex in the follicular fluid was reverted in other cycles in the same patients when hCG was properly administered. CONCLUSIONS: (1) This study emphasizes the importance of proper patients' and nurses' instructions for preparation of hCG injections and proper mixture of vehicle and powder before follicular aspiration. (2) In the absence of cumulus-corona-oocyte complex at aspiration, measure serum beta-hCG to ascertain whether hCG injection was administered or not. (3) Routine preoperative beta-hCG levels may be helpful to avoid unnecessary surgeries. PMID- 1633904 TI - The appearance of one-pronuclear human oocytes is associated with a better ovulation-induction response and successful pregnancy outcome. AB - OBJECTIVE: To study the relationship between the presence of one-pronuclear oocytes in in vitro fertilization (IVF) patients and ovulation-induction response, oocyte and embryo development, and clinical outcome. DESIGN: Retrospective analysis of 535 consecutive IVF retrievals. Retrievals in which one or more oocytes exhibited one pronucleus were compared with retrievals in which no one-pronuclear oocytes (control) were observed. The following one-pronuclear versus control subgroups were also examined: leuprolide acetate/human menopausal gonadotropin (LA/hMG) ovulation inductions, high estradiol (E2) response cases, and retrievals in which a large number of oocytes (greater than or equal to 15) were recovered. SETTING: Brigham and Women's Hospital, a tertiary care, university-affiliated hospital. PATIENTS: Three hundred forty-six IVF patients were treated between January 1989 and May 1991. MAIN OUTCOME MEASURES: Parameters examined included E2 concentration and number of follicles with maximum diameter greater than or equal to 12 mm on day of human chorionic gonadotropin administration; number of total and mature oocytes retrieved; total fertilization rates; number of embryos; and percent per retrieval of embryo transfers (ETs), clinical pregnancies, and ongoing-livebirths. RESULTS: The one-pronuclear patients had higher E2 levels and larger number of follicles, yielded significantly more total and mature oocytes, had a higher overall fertilization rate, produced more embryos, and had higher ET, clinical pregnancy and ongoing livebirth rates per retrieval than did the control patients. Analysis of the subgroup populations revealed no significant differences in the majority of the main outcome measures studied; however, the one-pronuclear patients yielded significantly more total and mature oocytes per retrieval. CONCLUSIONS: Although there was an increase in the clinical and ongoing-livebirth pregnancy rates (PRs) in one-pronuclear patients, this was probably associated with an improved ovulation-induction response in the one-pronuclear patients. They achieved significantly higher E2 levels, recruited a larger number of follicles, and yielded more oocytes and embryos per retrieval than the control patients. When only the LA/hMG, E2 greater than or equal to 1,500 pg/mL, or the greater than or equal to 15 oocytes/case retrievals were analyzed, the PRs were no longer different; however, the one-pronuclear patients still yielded significantly more total and mature oocytes per retrieval than the controls. Therefore, the appearance of one-pronuclear oocytes is probably associated with the maturation stage of the oocytes obtained and is indicative of an ovulation induction in which a large number of preovulatory, metaphase II oocytes have been recruited. PMID- 1633905 TI - Can a single, early quantitative human chorionic gonadotropin measurement in an in vitro fertilization-gamete intrafallopian transfer program predict pregnancy outcome? AB - STUDY OBJECTIVE: To assess the predictive value of a single serum human chorionic gonadotropin (hCG) measurement obtained on day 14, 15, or 16 after transfer in in vitro fertilization or gamete intrafallopian transfer pregnancies. DESIGN: Retrospective. SETTING: Assisted reproductive technology (ART) programs. PATIENTS: One hundred thirty-four consecutive pregnancies from two ART programs were reviewed. RESULTS: The incidence of livebirth was only 6% when day 14 to 16 hCG values were less than 100 mIU/mL, but increased to 82% with levels greater than 100 mIU/mL (P less than 0.001). The incidence of livebirth and multiple birth correlated with rising hCG levels. Only 1% (1/71) of pregnancies with serum hCG values greater than 100 mIU/mL was ectopic, and this case was a bilateral (double) ectopic. CONCLUSIONS: A single serum hCG measurement obtained 14 to 16 days after embryo or gamete transfer not only is diagnostic but also has good predictive value for pregnancy outcome. PMID- 1633906 TI - The administration of glucocorticoids for the prevention of ovarian hyperstimulation syndrome in in vitro fertilization: a prospective randomized study. AB - OBJECTIVE: To determine if the administration of glucocorticoids reduced the rate of ovarian hyperstimulation syndrome (OHSS) in high-risk patients after ovarian stimulation for in vitro fertilization (IVF). DESIGN: Prospective randomized study. PATIENTS: Thirty-one patients who were stimulated with human menopausal gonadotropin (hMG) after pituitary desensitization by gonadotropin-releasing hormone agonist and who developed greater than 20 follicles greater than 12 mm and/or had a serum estradiol (E2) level of greater than 10,000 pmol/L on the day of administration of human chorionic gonadotropin (hCG). INTERVENTIONS: Patients were randomly divided into two groups. Those who were randomized to receive glucocorticoids (group A) (n = 17) were administered intravenous hydrocortisone, 100 mg, immediately after ultrasound (US)-directed oocyte recovery. Prednisolone, 10 mg three times per day, was given for 5 days starting on the day of oocyte recovery followed by prednisolone 10 mg two times a day for 3 days and 10 mg/d for 2 days. Those in group B (n = 14) did not receive any glucocorticoid treatment. In both groups, luteal support was provided by intramuscular injections of gestone 100 mg/d. RESULTS: The two groups of patients were comparable in terms of age, duration of infertility, and total dose of hMG used. All had polycystic ovaries on US examination. On the day of hCG administration, the mean number of follicles in the two groups were 26.76 +/- 2.49 and 25.93 +/- 1.44 and the serum E2 concentration 13,404 +/- 710 and 13,915 +/- 901 pmol/L, respectively. There were no significant differences in the number of oocytes collected or in the fertilization, cleavage, and implantation rates in the two groups. The pregnancy rates per initiated cycle were 41.18% and 35.71%, respectively. Seven of the 17 patients (41.2%) who received glucocorticoids developed ovarian hyperstimulation syndrome compared with 6 of the 14 patients (42.9%) who did not receive glucocorticoids. CONCLUSIONS: Administrations of glucocorticoids to high risk patients did not reduce the rate of OHSS after ovarian stimulation for IVF. PMID- 1633907 TI - A study of the detection of sperm antibody in cervical mucus with a modified immunobead method. AB - OBJECTIVE: To develop a new immunobead binding test (IBT) procedure that will detect sperm antibody in cervical mucus (CM), especially in very small samples of mucus. DESIGN: After the interaction of donor sperm with bromelin-dissolved CM, the motile sperm cells were separated from other cells and debris and then tested with a standard immunobead method. SETTING: The CM and serum samples were obtained from a sequence of referred patients who were sent to this testing laboratory. PATIENTS: There were 60 women who provided 64 samples of CM and 41 samples of blood serum. They were partners in infertile couples. INTERVENTIONS: None. MAIN OUTCOME MEASURE: A useful distinction was made between positive and negative results for the mucus samples by this CM-IBT procedure. The usable samples of mucus could be as little as 0.05 g (wet weight). RESULTS: From the 60 women, seven mucus samples were positive; in the repeated testing, the same results were obtained with five of the six positive samples and seven of seven negative samples. CONCLUSION: This method (CM-IBT) can be clinically useful for detecting sperm antibody in CM, especially because it is effective for tiny samples. In this method, the motile sperm cells are better separated from the debris after the incubation step. When the IBT was applied to the serum samples from the same women, there was no correlation between serum-IBT and CM-IBT, showing that both materials must be tested. PMID- 1633908 TI - Novel model for study of human sperm chemotaxis. AB - OBJECTIVE: To develop and test an adequate method for the study of sperm chemotaxis. DESIGN: A model based on a double-chamber design and a matrix of 0.5% hyaluronic acid was used to test the response of human sperm to chemotactic signals from follicular fluid (FF). RESULTS: A plateau of migration was reached at 10 minutes of incubation; under this condition, 70% of sperm migrated toward chambers with FF, less than 20% to the opposite side, and the rest remained at the site of application. Intra-assay and interassay coefficients of variation using pools of FFs were 17.2% and 23%, respectively. CONCLUSION: These data confirm previous findings and support the use of this novel model for the study of chemotaxis on human gametes. PMID- 1633909 TI - The fertilization antigen-1 does not have proteolytic/acrosin activity, but its monoclonal antibody inhibits sperm capacitation and acrosome reaction. AB - OBJECTIVE: To determine if human sperm surface fertilization antigen exhibits proteolytic or acrosin activity and to investigate the mechanism(s) whereby monoclonal antibody (mAb) to fertilization antigen inhibits human sperm penetration of zona-free hamster ova. DESIGN: Proteolytic and acrosin activities of human fertilization antigen were determined. Acrosomal status, acrosin activity, and motion characteristics were evaluated after incubation of human sperm with immunoaffinity-purified mAb to fertilization antigen. SETTING: Academic research environment. PARTICIPANTS: Fertile donors used as controls for infertile patients for fertility evaluation. INTERVENTIONS: Human spermatozoa were treated with mAb to fertilization antigen and induced to undergo acrosome reaction using calcium ionophore A23187. MAIN OUTCOME MEASURES: Proteolytic and acrosin activities of fertilization antigen. Sperm penetration assay, acrosomal status, and motion parameters. RESULTS: Fertilization antigen does not exhibit proteolytic or acrosin activity; however, its mAb completely blocks human sperm penetration of zona-free hamster ova. The mAb to fertilization antigen inhibits ionophore-induced acrosome reaction and blocks development of the hyperactivated state of human sperm cells. CONCLUSIONS: Monoclonal antibody to fertilization antigen blocks fertilization by inhibiting capacitation and acrosome reaction. PMID- 1633910 TI - Immunoneutralization of gonadotropin-releasing hormone and subsequent treatment with testosterone Silastic implants in rats: an approach toward developing a male contraceptive. AB - STUDY OBJECTIVE: To determine the extent to which increasing doses of exogenous testosterone (T) administered via Silastic implants can restore spermatogenesis and fertility to rats made azoospermic by active immunization against gonadotropin-releasing hormone (GnRH). DESIGN: Male rats were made azoospermic by active immunization against GnRH. Increasing doses of exogenously administered T (via Silastic implants) were administered for 8 weeks, and testicular sperm concentration and ability to impregnate female rats were evaluated. SETTING: Reproductive Endocrinology Laboratory, Department of Obstetrics and Gynecology, University of Colorado Health Sciences Center, Denver, Colorado. ANIMALS: Sexually mature male Sprague Dawley rats (SASCO, Omaha, NE). RESULTS: Suppression of gonadotropins and azoospermia was achieved by actively immunizing rats against GnRH. Testosterone was capable of restoring quantitatively complete spermatogenesis and fertility in GnRH-immunized azoospermic rats. This relationship was dose-dependent, as evidenced by the partial restoration of spermatogenesis and fertility observed in animals replaced with smaller T Silastic implants. CONCLUSION: Gonadotropin-releasing hormone immunization and T filled Silastic implants may provide a model to study isolated gonadotropin deficiency and for the development of a reversible male contraceptive. PMID- 1633911 TI - Predictors of uterine volume reduction in women with myomas treated with a gonadotropin-releasing hormone agonist. AB - A retrospective analysis of 104 women with leiomyomata uteri treated with LA for at least 12 weeks demonstrated a negative correlation between the percent reduction in uterine volume and serum E2 concentration at treatment week 12. The patient's age, height, or pretreatment uterine volume were not correlated with the degree of uterine shrinkage. PMID- 1633912 TI - Massive ascites after leuprolide acetate administration for the treatment of leiomyomata uteri. AB - The administration of GnRH-a for decreasing the size of uterine leiomyomata is tolerated by most of our patients with a minimum of side effects and difficulty. An unusual case of pseudo-Meigs' syndrome developed after a single dose of depot LA that resulted in an emergent operation in this young woman. The treatment of large leiomyomata uteri with GnRH-a warrants careful clinical surveillance. PMID- 1633913 TI - What is the minimal uterine cavity needed for a normal pregnancy? An extreme case of Asherman syndrome. AB - There are no reports on the subsequent anatomic findings in women with intrauterine adhesions who conceived and delivered after therapy, but our experience indicates that most of these women menstruate and conceive normally. The recurrence of intrauterine adhesions, together with preserved fertility in this patient, suggest that fertility, while usually correlated with subsequent resumption of normal menstruation and anatomy, may sometimes be independent of these features. PMID- 1633914 TI - Pseudomyxoma peritonei associated with secondary infertility. AB - In summary, we report a case of secondary infertility attributed to pseudomyxoma peritonei caused by ruptured appendiceal mucocele. Resection of the tumor and visible mucinous ascites resulted in spontaneous conception. We hypothesize secondary infertility was caused by significant peritoneal inflammation and inhibition of sperm-oocyte interaction from the ascites. PMID- 1633915 TI - Pregnancy-associated subacute hemorrhage into a prolactinoma resulting in diabetes insipidus. AB - A young woman with a small pituitary tumor associated with hyperprolactinemia developed subacute intrapituitary hemorrhage during the third trimester of pregnancy and presented with central diabetes insipidus. Magnetic resonance imaging established the diagnosis. After transsphenoidal surgery, her visual findings resolved, and the patient had an uneventful spontaneous delivery. PMID- 1633916 TI - In vitro fertilization and embryo transfer in well-controlled, insulin-dependent diabetics. AB - Five IDD patients achieved strict preconception glycemic control and then underwent nine IVF-ET cycles. All patients had high E2 response with an adequate number of preovulatory oocytes retrieved and normal fertilization and cleavage rates; one conceived. Follicular fluid analysis revealed similar E2, P, A, hCG, PRL, and IGF-I levels to non-IDD controls. The source of the insulin detected in the FF of IDD patients was probably from the insulin doses administered intensively during the tight diabetes management; insulin was absent in non-IDD participants. It seems that patients with IDD have conventional responses to gonadotropin stimulation for IVF and their follicular milieu resembles that of non-IDD patients. Nevertheless, in view of the significant advantages of preconceptional diabetes control in regard to pregnancy outcome, they should be allowed to participate in IVF programs only after tight preconception metabolic control has been obtained. PMID- 1633917 TI - The effect of consecutive day inseminations on semen characteristics in an intrauterine insemination program. AB - This study demonstrates a statistically significant decrease in semen volume, sperm concentration, and sperm motility in samples obtained on the 2nd day of consecutive day inseminations in an IUI program. This diminution in semen characteristics persists despite sperm washing. The effects of a second ejaculation on semen parameters in oligospermic and asthenospermic men were mixed. Thus, in general, sperm-washing procedures cannot overcome the natural reduction in semen quality produced by frequent ejaculations. Clinicians may wish to use this information in timing IUI cycle inseminations. PMID- 1633918 TI - Motility longevity of sperm samples processed for intrauterine insemination. AB - This study demonstrates that sperm from men with male factor infertility and sperm obtained by electroejaculation have reduced motility longevity when compared with normal specimens. After 24 hours, normal samples lost only 34% of initial motility, whereas male factor patients lost 48%, and electroejaculation patients dropped 66%. Based on these data and previous clinical studies of insemination timing, it is recommended that sperm retrieval and artificial insemination for male factor infertility, especially when electroejaculation is necessary, be performed 24 to 36 hours after urinary detection of the LH surge or as close to the time of ovulation as possible. PMID- 1633919 TI - Sperm peritoneal recovery in infertile couples with male factors. AB - Several studies (1-3) dealing with the presence of spermatozoa in preovulatory peritoneal liquid have shown a low correlation with the situation prevailing in the uterine cervix. Although all previous studies have worked with normospermic populations, we aimed at answering whether alterations of seminal variables are associated with alterations in transportation along the feminine tract. Different sperm migrations (in concentration and motility) were found, depending on the number of seminal variables altered. PMID- 1633920 TI - Intrafollicular insemination for male factor infertility. AB - Intrafollicular insemination is a promising new development that may have a major impact on ART, notably in the treatment of male factor infertility. Reported is the first successful intrafollicular insemination in the United States and the first successful intrafollicular insemination for male factor infertility. Although the results are encouraging, further investigations are currently underway to critically evaluate intrafollicular insemination. PMID- 1633921 TI - Pathophysiology of ovarian hyperstimulation syndrome. PMID- 1633922 TI - Pathophysiology of ovarian hyperstimulation syndrome. PMID- 1633923 TI - Intravenous immunoglobulin therapy for recurrent abortion: "state of the art" or "experimental therapy"? PMID- 1633924 TI - Electronically united?--bibliographic omissions. PMID- 1633925 TI - Electronically united--at last editorial comment. PMID- 1633926 TI - Efficacy of immunotherapy preceding in vitro fertilization and embryo transfer. PMID- 1633927 TI - Selective salpingography technique. PMID- 1633928 TI - [Hormones and growth of cancer]. AB - Estrogen and androgen play essential roles in the development of breast cancer and prostate cancer, respectively. However, only 30% of breast cancer mass and 70% of prostate cancer mass are found to be hormone-dependent when they have been treated clinically. These findings show that hormone dependency of cancer disappears rather easily. Recently, it has been found that the growth of hormone dependent cancer is mediated through sex steroid-induced growth factors in an autocrine manner. Future studies on sex steroid-induced growth factor(s) will play important roles in order to understand the molecular mechanisms of the development and growth of breast cancer and prostate cancer. PMID- 1633929 TI - [The possibility of hereditary factors in the susceptibility to diabetic nephropathy in NIDDM]. AB - Diabetic nephropathy is the most important complication of diabetes, because it is a major cause of morbidity and mortality for diabetic subjects. Since not all subjects with diabetes are at risk of developing this complication, we conducted a study to determine if heredity might be a possible risk factor for diabetic nephropathy in non-insulin dependent diabetes. Twenty-one factors including inheritance of nephropathy and hypertension were investigated in 109 individuals with NIDDM: 50 patients without proteinuria (Group I), 20 patients with intermittent proteinuria (Group II), and 39 patients with continuous proteinuria (Group III) matched for age and duration of diabetes. Of those patients, 55 patients with inheritance of diabetes were also divided into three groups: 29 patients without proteinuria (Group I), 9 patients with intermittent proteinuria (Group II), and 17 patients with continuous proteinuria (Group III). Individuals in Groups II and III has significantly higher frequency of inheritance of diabetic nephropathy than those in Group I, and also individuals with inheritance of diabetic nephropathy had significantly higher frequency of diabetic nephropathy than those without it. Frequency of hypertension, retinopathy and body mass index in the past were significantly higher in subjects in Groups II or Group III than in those in Group I. There were no significant differences between subjects in Groups II and III. These findings suggest that susceptibility to diabetic nephropathy in NIDDM may be hereditary, although hypertension and obesity may also be important risk factors for diabetic nephropathy. PMID- 1633930 TI - [Role of growth hormone in the pathogenesis of dawn phenomenon in IDDM]. AB - The early morning hyperglycemia of diabetic patients has been commonly referred to as the "dawn phenomenon". Recently the nocturnal surges of growth hormone (GH) have been suggested as an important factor in the pathogenesis of the dawn phenomenon. In order to reassess the role of the nocturnal GH secretion in the dawn phenomenon, seven C-peptide negative diabetic patients were studied during 48hr-feedback control using a closed-loop insulin infusion device (Biostator). They received oral sleeping medication only on the first night (control) and sleeping medication with anticholinergic agent (pirenzepine 75mg) on the second night, and blood glucose, insulin requirements, GH and cortisol concentrations during 0000hr and 0700hr were measured. The peak of sleep-induced GH secretions was markedly suppressed by pirenzepine in comparison with the control night (19.8 +/- 3.7 vs. 3.0 +/- 1.2ng/ml; p less than 0.05). Insulin requirements during 0500hr and 0700hr were suppressed significantly by pirenzepine (3.0 +/- 0.2 vs. 2.0 +/- 0.2U/2hr; p less than 0.05). Insulin infusion ratio, i.e. insulin requirements during 0500hr and 0700hr divided by those during 0000hr and 0200hr, was decreased by pirenzepine (2.2 +/- 0.3 vs. 1.5 +/- 0.2; p less than 0.05). There were no significant differences in blood glucose and cortisol concentrations whether or not the anticholinergic agent was given. In conclusion, these results have shown that an anticholinergic agent may be useful in the management of insulin-treated patients with marked dawn phenomenon. PMID- 1633931 TI - [Forty-one cases of Cushing's syndrome: a comparison between Cushing's syndrome (adrenal adenoma) and Cushing's disease (adrenal hyperplasia)]. AB - We experienced 41 cases of Cushing's syndrome (12 males and 29 females, 15 years old - 65 years old) during the last 20 years. These included 20 patients with unilateral adrenal adenoma (Cushing's syndrome), 19 patients with bilateral adrenal hyperplasia (Cushing's disease), one patient with adrenal carcinoma and one patient with primary adrenocortical nodular dysplasia (PAND). Moreover, these cases included some special ones, i.e. 5 cases with destructive thyroiditis after treatment, 2 cases with aggravation of arthritis after treatment, a case of Carney's complex with PAND, one case with paradoxical response to dexamethasone, and one case combined with empty sella syndrome. The most specific clinical signs were moon face (95% occurrence), hypertension (95%) and subcutaneous bruising (80%). Other significant signs were eye edema (66%), buffalo hump (68%), subcutaneous purpura (63%) and osteoporosis (49%). Skin striae was not a common sign in our cases (41%). Renal stone was observed in only 20% of our patients but was a significant sign in this syndrome. There was no difference in the occurrence of each clinical sign between Cushing's syndrome and Cushing's disease. The elevation of white blood cell count (WBC) and serum sodium, a decrease of serum potassium, and a decrease of reabsorption of phosphate (%TRP) were observed. Thyroid-stimulating hormone (TSH) and human growth hormone (HGH) were suppressed in patients with Cushing's syndrome and patients with Cushing's disease. These results were consistent with those of previous reports. However, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) were high in those patients with Cushing's syndrome and those with Cushing's disease. Oral glucose tolerance test was carried out in 34 patients before and after treatment. Thirty-one percent of those had diabetes mellitus and 26% had impaired glucose tolerance (IGT). The response of IRI in this test was high in patients with Cushing's syndrome and patients with Cushing's disease, and decreased 4 weeks after treatment in those with Cushing's syndrome but remained high in those with Cushing's disease. Plasma ACTH level and urinary 17-OHCS excretion were significantly higher in Cushing's disease than in Cushing's syndrome. During an 8mg-high-dose dexamethasone suppression test, urinary 17-OHCS excretion in 13 of 14 patients with Cushing's disease (93%) was suppressed by more than 50% of baseline on the second day of testing. However, all of 18 patients with Cushing's syndrome, who had an 8mg-dexamethasone suppression test, failed to suppress urinary 17-OHCS by 50% of baseline.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1633932 TI - The gram-negative outer membrane: structure, biochemistry and vaccine potential. PMID- 1633933 TI - The effect of Cu(II) ions on the optical rotation of heparin. PMID- 1633934 TI - Growth substances in context: a decade of sensitivity. PMID- 1633935 TI - The pyruvate kinase of Thermoplasma acidophilum: purification, kinetic characterisation & use as a phylogenetic marker. PMID- 1633936 TI - Inter-species variants of the 5-HT3 receptor. PMID- 1633937 TI - Enzyme activity in organic media. PMID- 1633938 TI - Muscarinic receptor subtypes: inositol phosphates and intracellular calcium. PMID- 1633939 TI - Multiple heterotrimeric guanine nucleotide binding proteins: roles in the determination of cellular signalling specificity. PMID- 1633940 TI - The generation of free acid SBFI within the matrix of isolated rat heart mitochondria and its use to estimate matrix [Na+]. PMID- 1633941 TI - Factors affecting the steady-state distribution of lithium in the sheep-heart Purkinje fibre. PMID- 1633942 TI - Mitochondrial Ca2+ transport and the role of matrix Ca2+ in mammalian tissues. PMID- 1633943 TI - Hormonal regulation of the glucose transporter GLUT I in the lactating rat mammary gland. PMID- 1633944 TI - Intracellular calcium measurements in response to histamine stimulation in DDT1 MF-2 cells. PMID- 1633945 TI - Polarimetry of mixtures of Cu(II) ions and chemically modified heparins. PMID- 1633946 TI - Antibody engineering. PMID- 1633947 TI - Catalytic antibodies--a new window on protein chemistry. PMID- 1633948 TI - Beetroot and red urine. PMID- 1633949 TI - Mechanism and regulation of galactomannan biosynthesis in developing leguminous seeds. PMID- 1633950 TI - Properties of immobilised bromelain. PMID- 1633951 TI - Immune-mediated cell separation methods. PMID- 1633953 TI - Rat liver L-threonine dehydrogenase. PMID- 1633952 TI - Immunochemical tests of potential fertility. PMID- 1633954 TI - Near infra-red reflection measurements and the applicability of the absorption law. PMID- 1633955 TI - Cloning and sequence determination of the feline calicivirus strain F9. PMID- 1633956 TI - Alginates: biosyntheses and some structure-function relationships relevant to biomedical and biotechnological applications. PMID- 1633957 TI - Gel retardation analysis of ribonucleotide reductase gene expression in African swine fever virus. PMID- 1633958 TI - Isolation of a gene from Xenopus borealis containing a paired box. PMID- 1633959 TI - Decrease in carboxylate absorption during heparin-poly L-lysine interaction. PMID- 1633960 TI - A sequence comparison of the VP72 gene of African swine fever virus. PMID- 1633961 TI - Kinetic evidence for the existence of an unstable intermediate in the trinitrophenylation-induced rhodanese inactivation reaction. PMID- 1633962 TI - Inactivation of glucose-6-phosphate dehydrogenase from various sources by a bifunctional isothiocyanate. PMID- 1633963 TI - General acid-base catalysis of 2,4,6-trinitrobenzene-sulphonate-induced rhodanese inactivation. PMID- 1633964 TI - Restoration of rat liver L-threonine deaminase by pyridoxamine 5'-phosphate. PMID- 1633965 TI - Multiple-specular-reflectance i.r. spectroscopy of glycosaminoglycan cetylpyridinium complexes. PMID- 1633966 TI - Drug interference in the 2,2'-bicinchoninic acid protein assay. PMID- 1633967 TI - Bacterial cellulases. PMID- 1633968 TI - Problems in the interpretation of ATP concentration in blood fractions. PMID- 1633969 TI - Primer extension analysis of mouse U7 small nuclear RNA gene expression. PMID- 1633970 TI - Fungal cellulases. PMID- 1633971 TI - Purine metabolism in normal and HIV-1 infected lymphocytes. Purine nucleotide content. PMID- 1633972 TI - Purine metabolism in normal and HIV-1 infected lymphocytes. Analysis of nucleotides through HPLC. PMID- 1633973 TI - Physical map of a 257 kilobase-pairs region from the genome of Halococcus saccharolyticus. PMID- 1633974 TI - Extraction of a calcification inhibitor from Corallina officinalis. PMID- 1633975 TI - Thermodynamics of talin and talin-vinculin binding to G-actin. PMID- 1633976 TI - Elicitation of peroxidase production in cell suspension cultures. PMID- 1633977 TI - PCR amplification of specific cDNA sequences using mixed oligonucleotide primers- a cautionary note. PMID- 1633978 TI - The effect of immunophotodynamic therapy using the monoclonal antibody HMFG-1 linked to hematoporphyrin on MCF-7 cell in vitro. PMID- 1633979 TI - The relationship between 111In-labelled immunoscintigraphy and serum CA-125 levels in ovarian carcinoma patients postchemotherapy. PMID- 1633980 TI - Identification of a dipeptidyl aminopeptidase type-II in the cytosolic fraction of bovine brain. PMID- 1633981 TI - Treatment of hypothyroid rats with T2 (3,5-di-iodo-L-thyronine) rapidly stimulates respiration in subsequently isolated mitochondria. PMID- 1633982 TI - Chemical production of bifunctional antibodies. PMID- 1633983 TI - Effects on oral bacteria of a peptide derived from human cathepsin G. PMID- 1633984 TI - Respiration deficiency in the pathogenic yeast, Candida albicans. PMID- 1633985 TI - Pathogenicity of Xenorhabdus luminescens. PMID- 1633986 TI - Stress responses of Bacillus subtilis. PMID- 1633987 TI - Enzymatic incision of UV-irradiated DNA at sites of purine photoproducts. PMID- 1633988 TI - Molecular cloning and characterization of the lux genes from the secondary form of Xenorhabdus luminescens, K122. PMID- 1633989 TI - Increased calpain activity in skeletal muscle of rats maintained on caloric restricted and fasting dietary regimes. PMID- 1633990 TI - Starch granules large and small. PMID- 1633991 TI - Evidence for the presence of GTP-binding proteins in tobacco leaf and maize hypocotyl plasmalemma. PMID- 1633992 TI - Purification and conjugation of anti-insulin IgG from guinea pig serum for use in proinsulin immunoassay. PMID- 1633994 TI - Streptavidin production by Streptomyces avidinii in a laboratory fermenter. PMID- 1633993 TI - The concanavalin A-glycoprotein interaction as a convenient method for the assay of endoglycosidases. PMID- 1633995 TI - Shake flask studies of streptavidin production in synthetic and complex media. PMID- 1633996 TI - X-irradiation- and carcinogen-induced proteins in cultured CHO cells. PMID- 1633997 TI - Identification of genes for the ethylene-forming enzyme and inhibition of ethylene synthesis in transgenic plants using antisense genes. PMID- 1633998 TI - Dye-mediated photodynamic inactivation of Bacillus subtilis. PMID- 1633999 TI - The role of calcium in the induction of apoptosis in human tumour cell lines. PMID- 1634000 TI - The regulatory role of zinc in apoptosis in human tumour cell lines. PMID- 1634001 TI - Sensitivity of protein phosphorylation in tobacco thylakoids to protein kinase C inhibitors and synthetic peptides. PMID- 1634002 TI - Control of cell division in plants. PMID- 1634003 TI - TNF-induced, cytotoxicity-linked IL6 gene expression in L929 cells may require factors other than NF-kappa B. PMID- 1634004 TI - Maltogenic alpha-amylase of Saccharomonospora viridis. PMID- 1634005 TI - Effects of phosphate on the binding of FMN and riboflavin by apoflavodoxin from Desulfovibrio vulgaris (Hildenborough). PMID- 1634006 TI - Apoptosis induced by Actinomycin D, Camptothecin or Aphidicolin can occur in all phases of the cell cycle. PMID- 1634007 TI - A Fasciola hepatica cathepsin L proteinase prevents the adherence of eosinophils to newly excysted juveniles. PMID- 1634008 TI - Purification and characterisation of a cysteine proteinase secreted by Fasciola hepatica. PMID- 1634009 TI - Patterns of exoprotein production in isolates of Staphylococcus schleiferi and Staphylococcus lugdunensis. PMID- 1634010 TI - Plasminogen activator inhibitor type 1 and 2 in human breast cancer. PMID- 1634011 TI - Specific immune detection and partial purification of G-proteins from Arabidopsis thaliana. PMID- 1634012 TI - Expression of auxin-responsive genes in soybean and transgenic tobacco. PMID- 1634013 TI - The forest, the trees and the anterior pituitary. PMID- 1634014 TI - Autoradiographic demonstration of in vivo 125I-growth hormone-releasing hormone (GHRH) binding by human GH-secreting pituitary adenomas transplanted on athymic nude mice. AB - This study was designed for the purpose of investigating a method for in vivo tumor labelling of human GH (hGH) secreting pituitary adenomas. Pituitary adenoma tissue removed from four acromegalic patients was transplanted into 62 athymic nude mice. After positive GHRH stimulation tests 125I-GHRH(1-44) NH2 was injected intravenously (i.v.) in ten nude mice. 10 min after 125I-GHRH injection, the nude mice were sacrificed, the transplants excised and prepared for light microscopical autoradiography. The mouse pituitary and skeletal muscle specimens served as controls. After the i.v. injection of 125I-GHRH we observed a marked accumulation of silver grains within the adenoma tissue indicating tumor labelling. This study is a first step in investigating a new method for labelling small residues of hGH secreting pituitary adenomas intraoperatively. PMID- 1634015 TI - Synergistic interaction of growth factors and albumin in regulating estradiol synthesis in breast cancer cells. AB - Estradiol 17 beta-hydroxysteroid dehydrogenase acts to convert estrone to the biologically active estrogen, estradiol, in breast tumors and MCF-7 breast cancer cells in vitro. In this study we have examined the ability of albumin to influence the effect of growth factors (insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha)) and cytokines (interleukin (IL)-1, IL-6) on estradiol 17 beta-hydroxysteroid dehydrogenase activity in MCF-7 cells. IGF-I (80 ng/ml) or albumin (30 micrograms/ml) stimulated estradiol 17 beta-hydroxysteroid dehydrogenase activity by 144% and 102% (p less than 0.01). The combination of IGF-I and albumin, however, produced a marked (704%) synergistic stimulation of estradiol 17 beta hydroxysteroid dehydrogenase activity. EGF or TGF alpha failed to stimulate estradiol 17 beta-hydroxysteroid dehydrogenase activity and no synergism with albumin was detected. IL-1 (10 ng/ml), but not IL-6, also stimulated estradiol 17 beta-hydroxysteroid dehydrogenase activity and acted synergistically with albumin to stimulate enzyme activity. MCF-7 cells were shown to specifically bind 125I albumin and binding is increased by pretreatment of cells with IGF-I (80 ng/ml) for 48 h. It is concluded that the synergism that results from treating MCF-7 cells with albumin and IGF-I may result from increased albumin uptake and subsequent biological effect. PMID- 1634016 TI - The priming effect of luteinizing hormone-releasing hormone (LHRH) but not LHRH induced gonadotropin release, can be prevented by certain protein kinase C inhibitors. AB - The priming effect of LHRH in vitro (which results in increased responsiveness of gonadotropes to both LHRH receptor-mediated and receptor-independent stimuli) is brought about by an unknown mechanism. The present results indicate that induction of the LHRH priming effect is inhibited in a concentration-dependent manner by the protein kinase C (PKC) inhibitors staurosporine, K252a, H7 and by the novel highly-selective PKC inhibitor, Ro 31-8220. In contrast, a range of other compounds that are relatively selective inhibitors of other kinases such as tyrosine kinases and Ca2+/calmodulin-dependent kinases were unable to prevent priming. The PKC inhibitors prevented priming without affecting initial LHRH induced gonadotropin secretion. Thus, the priming-elicited increment in secretion was selectively removed, restoring hormone release to the level measured during an initial response to LHRH. Similar results were obtained on different days of the estrous cycle where the magnitude of the priming effect varies. Experiments on the time course of PKC inhibitor action revealed that the critical period was in the induction of the priming effect, not its expression. The PKC inhibitors had neither acute nor delayed effects on gonadotropin secretion induced by ionomycin. Staurosporine, K252a and Ro 31-8220 inhibited LHRH priming with identical potencies to their inhibition of phorbol ester-induced gonadotropin secretion. The reduced potency of H7 seen on LHRH priming compared to phorbol ester-induced gonadotropin release parallels results seen with this inhibitor on phorbol ester-induced secretion of growth hormone (Johnson and Mitchell (1989) Biochem. Soc. Trans. 17, 751-752) and on the pharmacological characteristics of PKCs partially purified from anterior pituitary tissue. In all aspects of this study, effects on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion appeared to be entirely similar. PMID- 1634017 TI - Ovarian aromatase cytochrome P-450 mRNA levels correlate with enzyme activity and serum estradiol levels in anestrous, pregnant and lactating rats. AB - We examined the changes in P-450AROM mRNA, aromatase enzyme activity and serum estradiol levels (E2) in anestrous, pregnant mare's serum gonadotropin (PMSG) treated immature, pregnant, and lactating rats to determine if: (a) the various mRNA species encoding P-450AROM in rat ovarian tissue are differentially expressed during different hormonal states, and (b) a positive relationship exists between P-450AROM mRNA and enzymatic activity in rat ovarian tissue and serum estradiol levels from the same animals. Utilizing three different cDNAs encoding rat P-450AROM, levels of P-450AROM mRNA were determined by RNA blot analysis and scanning densitometry. Probe 1, a 5' probe, detects all three P 450AROM mRNA species in rat ovarian tissue (i.e. at 1.7, 2.2 and 2.7 kb). Probe 2 contains an unspliced intronic sequence in place of the heme-binding domain at its 3' terminus and thus the mRNA detected by this probe must encode a nonfunctional aromatase protein. Only the two smaller (i.e. nonfunctional) mRNA species at 1.7 and 2.2 kb are detected by probe 2. Probe 3 contains the heme binding region and hybridizes to principally the largest mRNA transcript at 2.7 kb (but hybridizes also to a 1.7 kb mRNA transcript). Aromatase enzyme activity was measured by using a saturating concentration of [1 beta-3H]testosterone as substrate in the [3H]water-release assay while serum estradiol levels were determined by radioimmunoassay. In immature rats (IR) or lactating animals (LA) P 450AROM mRNA was not detectable along with low serum estradiol (IR approximately 2.8 pg/ml; LA approximately 0.2 pg/ml) and aromatase activity levels (IR approximately 0.8 pmol/h per mg protein; LA less than 0.5 pmol/h per mg protein). Anestrous animals treated with 5 IU of PMSG resulted in a clear increase (24 h later) in P-450AROM mRNA levels, in concert with a 4-fold increase in serum E2 (approximately 12.5 pg/ml) and aromatase activity (approximately 4.2 pmol/h per mg protein). During pregnancy, all three mRNA species were clearly detectable, but low serum E2 levels (approximately 0.6 pmol/ml) and P-450AROM mRNA abundance were observed at 3 days of gestation (DG). Levels of all three P-450AROM mRNA species increased markedly at 15 and 18 DG; thereafter, the levels declined at 20 DG and further decreased at 22 DG. However, regardless of the probe utilized (probe 1, 2 or 3) in the RNA blot analyses, the mRNA transcripts detected by each probe were expressed in a concerted fashion with respect to abundance and pattern.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1634018 TI - Comparison of the biological and immunological properties of glycosylation deficient human chorionic gonadotropin variants produced by site directed mutagenesis and chemical deglycosylation. AB - Appropriate glycosylation of gonadotropins is essential for the full expression of their biological activity. In this investigation we have compared the properties of glycosylation deficient human chorionic gonadotropin (hCG) produced by chemical deglycosylation (HF treatment--DG-hCG) or recombinant techniques (site directed mutagenesis). Among the recombinant hCG molecules secreted into the culture medium, the following variants containing selective N-glycosylation deletions at delta alpha 1 or delta alpha 1,2 or in both subunits could not stimulate steroidogenesis in mouse Leydig tumor cells (MA-10 cell line) and in this respect were very similar to DG-hCG. The other variants were fully active like native hCG, but the alpha + delta beta 1,2 recombinant hCG was a partial agonist. In radioimmunoassay with antibodies against native hCG, the DG-hCG as well as all recombinant hCG variants, including the wild type (WT), were similar. However, with antisera against DG-hCG or affinity purified antibodies specific to DG-hCG the alpha/delta 1,2 beta mutant, the WT hormone and native hCG were less active. In this assay mutants containing N-glycosylation deletions in the alpha subunit as well as the delta alpha 1,2/delta beta 1,2, variant showed higher activity. A similar pattern was evident in reaction with a selected monoclonal antibody showing preferential binding of 125I-labeled DG-hCG (antagonist). Affinity purified antibody directed against native hCG conformation was successful in converting DG-hCG and some inactive glycosylation deficient variants into an active form by stimulating progesterone in MA-10 cells. These data suggest that there are similarities as well as subtle differences in conformation of DG-hCG and various recombinant hCG molecules.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634019 TI - Regulation of inhibin beta B-subunit mRNA expression in rat Sertoli cells: consequences for the production of bioactive and immunoreactive inhibin. AB - In Sertoli cells from 21-day-old rats, the expression of the mRNA encoding the alpha-subunit of inhibin, and the production of immunoreactive inhibin are stimulated by follicle-stimulating hormone (FSH). In contrast, the amount of beta B-subunit mRNA is not increased after FSH treatment of the cells, and the ratio between bioactive and immunoactive inhibin decreases after stimulation with FSH. These data suggest that the beta B-subunit is the limiting factor in the production of bioactive inhibin. The aim of the present experiments was to investigate the effect of changes in the amount of beta B-subunit mRNA on the production of bioactive and immunoreactive inhibin. During early postnatal testicular development, the relative amounts of the 4.2 kb and 3.5 kb mRNAs encoding the beta B-subunit of inhibin changed markedly. The meaning of this changing ratio between beta B-subunit mRNAs is not clear, since both mRNAs are actively translated, as demonstrated by polysomal analysis. The total amount of beta B-subunit mRNA correlated with the in vitro production of bioactive inhibin as published earlier. Prolonged stimulation of cultured Sertoli cells from 14-day old rats with 4 beta-phorbol 12-myristate 13-acetate (PMA) caused a decreased expression of the beta B-subunit mRNAs, presumably by down-regulation of protein kinase C. A similar effect was obtained after addition of the calcium ionophore A23187. Concomitantly, a decreased production of bioactive inhibin was observed. Furthermore, Western blotting revealed that secretion of the 32 kDa inhibin alpha beta-dimer was decreased, whereas secretion of the combination of the C-terminal part with the pro-region of the alpha-subunit was increased. It is concluded that the level of the beta B-subunit of inhibin is rate-limiting for the production of bioactive inhibin in cultured Sertoli cells, and that its expression can be influenced by modulation of protein kinase C, and/or intracellular calcium levels. PMID- 1634020 TI - Selections from current literature: treatment of hypertension. AB - The three papers reviewed for this issue deal with unrelated aspects of hypertension, illustrating the broad range of questions that still exist about optimal diagnosis and management. Physicians have for years been unsure about the efficacy, safety, and impact on morbidity of treating ISH. The result of these concerns has been that many, if not most patients with ISH never received treatment. The SHEP data are a powerful argument for routine treatment of ISH, which would represent a new standard of care for this condition. Only clinical experience and future trials will indicate whether treatment of ISH in the general population will be accompanied by the low incidence of side effects and morbidity observed in the more highly selected population of the SHEP trial. The study of Zeller et al. adds to the evidence that less is more, or at least the same, when it comes to treatment of hypertensive urgencies. The practice of oral 'loading' doses was not shown to improve therapeutic results. It is still not completely clear what criteria physicians should use in making a decision about inpatient parenteral therapy versus outpatient oral therapy. In patients with evidence of acute onset and end-organ injury, it is probably prudent to admit. In the absence of these risk factors, institution of an outpatient oral antihypertensive regimen can probably be accomplished with safety and at dramatically lower cost. The study of Koren et al. demonstrated a marked additional risk when LVH was present in hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634021 TI - Chronic illness in the community and the concept of 'social prevalence'. AB - General practice is an important source of information on the occurrence and distribution of chronic disease in the population. In this study, the burden of chronic illness was expressed as different indices of prevalence. Data were provided by 42 general practitioners in 15 computerized practices, collaborating in the Registration Network Family Practices of the University of Limburg in the Netherlands. Morbidity data concerning the actual health status of 25,357 subjects, as recorded by their GPs, were classified following the International Classification of Primary Care using the diagnostic criteria of the International Classification of Health Problems in Primary Care-2-Defined. The most frequent single disease was asthma (3.5%), while locomotor problems represented the most prevalent category (8.3%). The overall prevalence of chronic disease was 29.4%, with a clear positive correlation with age and, to a lesser extent, with a lower educational level. The 'social prevalence' of chronic illness (including individuals related to chronically diseased patients via their households) could be measured in a subset of the database (n = 4577), and amounted to 56%. It is concluded that the role of the GP as a family doctor involved with chronic disease concerns the majority of the general population. PMID- 1634022 TI - The general practitioner and laboratory utilization: why does it vary? AB - In a study of the practice patterns of 128 general practitioners in Northern Norway information concerning 6848 surgery consultations was registered. The ordering of haemoglobin and sedimentation tests was noted as well as urinalyses, forwarding of biological specimens (blood, urine, smears, etc) to other laboratories, and referrals for X-ray examinations. The extent to which doctors ordered these tests varied widely (haemoglobin 0-72% of encounters, urinalyses 0 70%, forwarding of tests 0-56%). Fee-for-service doctors ordered urine microscopy more frequently than did their salaried colleagues, but the ordering of haemoglobin or sedimentation test, and the forwarding of biological samples was about the same. Female and older doctors as well as doctors trained in Norway tended to request tests more often. Laboratory utilization was higher in municipalities with a high turnover of doctors, but the doctors' years of postgraduate experience per se did not affect the extent of test ordering. Tests were requested more often for female patients and with increasing age of the patient. However, only 10% of the variation in laboratory utilization was explained by the variables used in the analyses. This may imply that the medical condition at hand is the strongest determinant of test ordering behaviour. PMID- 1634023 TI - Diagnostic impact of the erythrocyte sedimentation rate in general practice: a before-after analysis. AB - Despite its frequent use and long history, little is known about the diagnostic impact of the measurement of the erythrocyte sedimentation rate (ESR) in general practice. We prospectively followed 362 patients who were seen by their general practitioner (GP) because of a new complaint, for which the GP wanted to know the ESR. The GPs recorded the most probable diagnosis, as well as their clinical judgements in terms of 'severe' and 'not severe', and the expected ESR values, before and after the determination of the ESR in the local hospital laboratory. Having compared the results before ESR determination with the results after, we conclude that ESR is valuable in reassuring the patient and the doctor when 'no pathology' is suspected rather than in confirming the presence of inflammatory diseases and malignancies. PMID- 1634024 TI - Continuity of care: general practitioners' knowledge about, and sense of responsibility toward their patients. AB - The aim of the present study was to examine the relations between continuity of care and the general practitioners' accumulated knowledge about their patients. A further objective was to evaluate the link between continuity of care and the doctors' sense of medical responsibility towards the patients. Emphasis was placed on the chronological, or longitudinal component of continuity of care. In a cross-sectional record study a representative sample of 133 Norwegian general practitioners each registered 30 consecutive consultations. Two aspects of longitudinal care were recorded: the duration of the patient-doctor relationship, measured as time from the first visit to the present, and the density, measured as the number of consultations (office or home visits) within the last 12 months. The physicians subjectively evaluated their accumulated knowledge about the patient's medical history, personality, and social network, on multinomic scales. Their sense of medical responsibility was indicated as one of three alternatives. Of 3990 possible recordings, 3918 (98%) were evaluated. In about one-third of all encounters the doctors reported extensive knowledge about their patients. It took at least one, and often 5 years, or at least 4-5 visits last year, to create such an extensive knowledge base. The physician's sense of responsibility increased more rapidly, and to a higher degree with the density of visits, than with duration of the relationship. The findings indicate firm links between longitudinal care and accumulated knowledge, and between longitudinal care and the doctors' sense of responsibility towards their patients. PMID- 1634025 TI - Factors associated with the decision to refer patients with anxiety disorders or sexual dysfunction. AB - The decision to refer patients to outside agencies is a complex one, seemingly related to patient, doctor and practice variables. Although there is a wide variation in referral rates between doctors, attempts to specify relevant demographic characteristics have been largely unsuccessful. The present study involves an examination of the factors which general practitioners report would affect their decision to refer, or not refer, patients portrayed in four case studies, two with anxiety disorders and two with sexual dysfunction. The results suggest that very different variables may be relevant for apparently similar conditions. The factor which most consistently distinguished between frequent and infrequent referers was the time they believed was required for treatment, but perceived responsibility for treatment was also important. Seventy per cent of the variance in referral decisions for sexual dysfunction but only 26% of the variance for anxiety disorders was accounted for by such variables as perceived expertise, time required for treatment and confidence in agencies. Demographic factors, such as age and level of training, were not associated with referral behaviour. Suggestions for further research, especially to do with the processes involved in decision making, are outlined. PMID- 1634026 TI - Determinants of maternal tolerance of vaccine-related risks. AB - In a time when informed consent requires knowledge of the risks and benefits of medical care and technology to be communicated to the public, perceptions of benefits and risks of these techniques and procedures take on special importance. The purpose of the present study was to examine the determinants of maternal tolerance of vaccine-related side-effects in their children. A questionnaire was sent to 226 mothers of young children in southwestern Ontario seeking their opinion of the benefits and risks of selected medical procedures. It asked them to identify the risk of serious reactions they would tolerate for a new vaccine with benefits similar to that of pertussis vaccine. The response rate to the questionnaire was 92%. This group of young, well-educated mothers had high regard for some of the most common procedures and treatments used in family practice. The less common and more invasive procedures (heart surgery, brain surgery) were viewed as carrying almost as much risk as benefit. Abortion was perceived as involving more risk than benefit. Levels of acceptable risk with respect to a hypothetical new childhood vaccine were determined. A risk level of 1 in 1 million was the most popular level of acceptable risk, chosen by 25% of the respondents. The next most frequently chosen risk level was 1 in 100,000, chosen by 22%. Tolerance of possible vaccine side-effects did not differ with maternal age, education or prior experience with adverse vaccine or drug reactions. A summary net benefit score was derived for four technologies commonly used in family practice (antibiotics, vaccinations, birth control pills and X rays).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634027 TI - Risk management in the community: lessons for family medicine. AB - Three polyurethane factories in Israel were examined using a combination of qualitative and quantitative methodologies. The study contrasts the effects of differing factory social and economic organization on occupational health and safety conditions as well as workers' attitudes and awareness. The central focus of the research addresses how each factory and community manages the risks associated with a particular industrial process. Surprisingly, the results show that the worker-owned and -operated plant, where knowledge and control of hazards was broadly shared and awareness high, had the worst safety, health, and hygiene conditions and outcomes. Worker involvement does not ensure worker protection and safety. These findings can be explained only by a careful examination of the social, economic, cultural and environmental settings in which they are embedded. Such an approach is well suited to family medicine research and training since it emphasizes the role of context on illness and disease. PMID- 1634028 TI - Life after divorce--a five-year follow-up study of divorced middle-aged men in Sweden. AB - Twenty-seven men, between 35 and 49 years of age, were asked via a questionnaire for information about their life circumstances (housing and working conditions, economic situation), actual symptoms, perceived health and health-related behaviour 5 years after they had divorced. The information was compared to corresponding data from an earlier study carried out within 7 months after the legal divorce. Housing conditions and personal economy had improved and working conditions were still satisfactory. Perceptions of health were more positive and in particular earlier, frequently recorded psychological symptoms (uneasiness, anxiety, depression) had diminished. Alcohol and smoking habits remained unchanged and common, especially among manual workers with more than one divorce. Men living in a stable relationship with a new partner or who had custody of children had fewer social and medical problems than men living alone. These findings support the connection between social support and health. PMID- 1634029 TI - Doctors' interviewing technique and its response to different booking time. AB - There is a burgeoning literature on communication in general practice. It is often assumed that trained GPs know and practice the techniques described, but that time is a major constraint. In two experimental studies patients were given shorter or longer appointments, and the doctors' use of different verbal interventions was measured. Our analysis focused on how individual doctors varied in their use of interviewing techniques according to the time available. When more time was available some interventions were used more frequently by all doctors, but for other interventions the response was variable. For example, GPs who normally used facilitation frequently used it more often when greater time was available, whereas doctors who used this technique less frequently tended not to change when more time was available. This suggests that, at least in the short term, there is a differential response to changes in the time available in the consultation, with increased time being a necessary but not sufficient condition to promote the greater use of the communication techniques which doctors use less frequently. PMID- 1634030 TI - What can doctors do to achieve a successful consultation? Videotaped interviews analysed by the 'consultation map' method. AB - Positive consultations, where both the GP and the patient had a positive impression, were compared with negative consultations, where both the GP and the patient had a negative impression. The consultations were compared with respect to tasks listed by Pendelton et al. in their 'consultation map', constituting satisfying and efficient consultation. The determining points in the positive consultations were that the GP and the patient were in agreement about the reason for the consultation and that the GP asked about the patients' ideas and concerns or health beliefs. In consequence, the GP used more time to achieve a share understanding with the patient and involved the patient in the management. This last point seemed to be the most discriminating between the positive and the negative consultations. PMID- 1634031 TI - Worry: a particular determinant of consultation illuminated. AB - In this study, exploring the worry experienced by patients in the GP waiting room and the reasons for being worried, 791 patients completed a structured questionnaire just before they consulted their GP, and afterwards. The perceptions of the patients concerning the complaint and the need for more information about the complaint played an important role in the degree of worry. Patients who wanted more information about the complaint were more worried than the patients who did not feel they needed more information. Not surprisingly, the more serious the patients perceived the complaint to be and the greater the perceived chance of serious disease, the more worried they were. General health status and frequency of consultations per year were related to the degree of general worry. According to the patient self-reports, worry was almost never due to information from the mass media or from other persons, or to a concern for the consultation itself. Patients generally evaluated the consultation as positive with respect to the way their worry was discussed. The decrease in worry after consulting the GP, in patients who were positive about the consultation was significantly higher than that in patients who were less positive. The theoretical and practical implications of this study are discussed. PMID- 1634032 TI - Patient satisfaction and the detection of psychiatric morbidity in general practice. AB - This study explores the relationship between the detection of psychiatric illness during general practice consultations and patient satisfaction. Psychiatric illness was defined as a score of greater than or equal to 3 on the 12-item General Health Questionnaire (GHQ-12). The hypothesis was that patient satisfaction would be higher after consultations during which psychiatric illness was correctly identified by the GP than after those during which it was 'missed'. Two hundred and twenty two patients attending seven doctors at one inner London practice participated. One hundred and ten patients (50%) scored greater than or equal to 3 on the GHQ-12. The GPs classified 76 of these 110 patients as having a psychiatric component to their illness and 34 as having an entirely physical illness. Only one significant difference in satisfaction was found between these two groups--patients in whom psychiatric illness was correctly identified reported more benefit from the consultation than patients in whom psychiatric illness was present but 'missed'. Possible explanations for the largely negative findings are discussed including the difficulties of measuring patient satisfaction and the distinction between detection and management of psychiatric illness in general practice. PMID- 1634033 TI - Research training for general practitioners: an experiment in The Netherlands. AB - One of the great problems in the field of primary health care research is the lack of qualified general practice researchers. The same is true for General Practitioners working in the University Departments of General Practice. Therefore the Department of General Practice at the University of Limburg in Maastricht in the Netherlands, developed a one-year research training programme for young General Practitioners. The aim was to provide a sufficient number of trained and qualified staff members in primary health care research for the various University Departments of General Practice. This article describes the main ideas behind this training course, as well as its contents and characteristics. PMID- 1634034 TI - Qualitative research and family practice: a marriage made in heaven? AB - Recent years have seen the development of interest in the usefulness of qualitative methods in family practice research. This paper shows how the underlying concerns of family practice medicine parallel those of the qualitative research tradition. After contrasting the philosophical underpinnings of both quantitative and qualitative methods, we go on to describe the methodological commitments of qualitative research. We relate this emerging debate within family practice to that which has taken place in other disciplines, particularly that of education. We discuss the relative strengths of qualitative and quantitative methods, and argue that these two traditions have complementary contributions to make to the discipline of family practice medicine. PMID- 1634035 TI - Patient perceptions of continuity of care: is there a socioeconomic factor? AB - This study aimed to assess perceptions of continuity of care by patients from different socioeconomic areas using focus group interviews augmented by postal replies. Patients were randomly selected from two contrasting primary medical care locations: a middle class suburb and a less affluent suburb in Adelaide, South Australia. The Ethnograph was used to analyse the content of the interviews and postal responses. Analysis used the framework described by Curtis and Rogers in the USA and Freeman in the UK. The response rate was much lower from the lower socioeconomic group (5% focus group; 20% when postal replies included). They emphasized access factors and importance of records, and alleged situations where they were taken too casually and their problems were not dealt with. Those from the middle class area (response rate 25%) emphasized interpersonal ('art of care') factors and were more likely to use their presenting problem as a criterion to decide whether they needed to postpone the problem to a time when they could see their personal doctor. Focus groups can be useful evaluation tools in general practice, but oversampling of lower socioeconomic groups is needed. Continuity of care should be considered as an aid to consistent quality of care, rather than its essence. Well controlled intervention-outcome studies in different types of practice organization in differing socioeconomic situations will increase our understanding of continuity of care. PMID- 1634036 TI - Goals and methods of research: the challenge for family medicine. AB - This article suggests that motivations to engage in research, as in any other human activity, are both explicit and implicit. Explicit motivations tend to be objective and rationalist, concerned with such goals as the advancement and organization of knowledge. But implicit motivations, the 'hidden agendas' of research, also exist and can influence the objectives, methods, and conclusions of the research process. In addition, a highly affectively charged activity such as research also develops its own set of symbolic meanings, which further complicate its various expressions. In this article, three such symbolic meanings are identified: purpose and seriousness; maturity and adulthood; and legitimacy and belonging. The article highlights qualitative research as a methodology compatible with much of family medicine's philosophy and theoretical foundations; and discusses the role of behavioural scientists in participating in a research agenda for the field. The article concludes with a plea for the discipline of family medicine to opt for authenticity in research, rather than settling for a superficial legitimacy in the eyes of other medical specialties. PMID- 1634037 TI - Turning anecdotes into data--the critical incident technique. AB - This article describes the critical incident technique and offers practical guidance on how the technique can be used to investigate dilemmas in medicine. It extols the particular virtue of this research method for general practice that it can be used to exploit the natural tendency of doctors to tell anecdotes. How the principles of the technique relate to significant event analysis, a form of medical audit, is also discussed. PMID- 1634038 TI - A revolution in medicine like no other. PMID- 1634039 TI - Molecular biology: impact on human disease. PMID- 1634040 TI - Assessing the underlying pattern of human germline mutations: lessons from the factor IX gene. AB - Germline mutations cause or predispose to most disease. Hemophilia B is a useful model for studying the underlying pattern of recent germline mutations in humans because the observed pattern of mutation in factor IX more closely reflects the underlying pattern of mutation than the observed pattern for many other genes. In addition, it is possible to identify and correct for biases inherent in ascertaining only those mutations that cause hemophilia. Aspects of the pattern of germline mutation in the factor IX gene are becoming clear: 1) in the United States, two-thirds of mutations causing mild disease arose from three founders whereas almost all the mutations resulting in either moderate or severe disease arose independently, generally within the past 150 years; 2) direct estimates of the rates of mutation in humans indicate that transitions are more frequent than transversions, which in turn are more frequent than deletions and insertions; 3) transitions at CpG are elevated approximately 24-fold relative to transitions at non-CpG dinucleotides; 4) transversions at CpG are elevated approximately eightfold relative to transversions at non-CpG dinucleotides; 5) the sum total of the dinucleotide mutation rates produces a bias against G and C bases that would be sufficient to maintain the G+C content of the factor IX gene at its evolutionarily conserved level of 40%; and 6) the pattern of mutation is similar for Caucasians residing in the United States and for Asians residing in Asia. Two ideas emerge from this and from an analysis of the pattern of recent deleterious mutations compared with ancient neutral mutations that have been fixed during evolution into the factor IX gene. First, the bulk of germline mutations are likely to arise from endogenous processes rather than environmental mutagens. Second, the factor IX protein is composed mostly of two classes of amino acids: critical residues in which all single-base missense changes will disrupt protein function, and "spacer" residues in which the precise nature of the residue is unimportant but the peptide bond is necessary to keep the critical residues in register. More work is necessary to assess the veracity and generality of these ideas. PMID- 1634041 TI - Leber's hereditary optic neuropathy: a model for mitochondrial neurodegenerative diseases. AB - A number of human diseases have been attributed to defects in oxidative phosphorylation (OXPHOS) resulting from mutations in the mitochondrial DNA (mtDNA). One such disease is Leber's hereditary optic neuropathy (LHON), a neurodegenerative disease of young adults that results in blindness due to atrophy of the optic nerve. The etiology of LHON is genetically heterogeneous and in some cases multifactorial. Eleven mtDNA mutations have been associated with LHON, all of which are missense mutations in the subunit genes for the subunits of the electron transport chain complexes I, III, and IV. Molecular, biochemical, and population genetic studies have categorized these mutations as high risk (class I), low risk (class II), or intermediate risk (class I/II). Class I mutations appear to be primary genetic causes of LHON, while class II mutations are frequently found associated with class I genotypes and may serve as exacerbating genetic factors. Different LHON pedigrees can harbor different combinations of class I, II, or I/II mtDNA mutations, as shown by the complete sequence analysis of the mtDNAs of four LHON probands. The various mtDNA genotypes included an isolated class I mutation, combined class I+II mutations, and combined class I/II+II mutations. The occurrence of such genotypes supports the hypothesis that LHON may result from the additive effects of various genetic and environmental insults to OXPHOS, each of which increases the probability of blindness. PMID- 1634042 TI - Genetic factors in the etiology and pathogenesis of autoimmunity. AB - Family and population studies indicate that several different genes can increase susceptibility to autoimmune diseases. Established genetic risk factors include genes encoding histocompatibility molecules, complement proteins, immunoglobulins, peptide transporter proteins, and genes controlling the production of sex hormones. Each factor may independently enhance the immunogenicity of autoantigens, either by increasing their processing and presentation by B lymphocytes and macrophages or by increasing the chance for recognition by autoreactive T and B lymphocytes. Genetic factors may also influence immune responses to infectious agents that can trigger autoimmunity. Because of the somatic generation of immune diversity, genetically identical individuals have different immune systems. The ability of genetic diagnosis to predict autoimmune disease in outbred populations cannot easily exceed the disease concordance rates in monozygotic twins, which usually are less than 50%. However, genetic diagnosis can target populations that should be monitored for serologic evidence of autoimmunity, which may precede clinical signs and symptoms. In the future, it may be possible to match different forms of immunotherapy with specific genetic defects. PMID- 1634043 TI - The diffusion of new genetic tests for predicting disease. AB - This paper examines the pathways by which new genetic tests will become available to the public. In view of the scarcity of genetic specialists, the pathway is likely to involve primary care physicians. Other pathways entail state-mandated testing, community-based programs, or testing by laboratories without much involvement of primary care physicians. When testing does become available the "destination" will be either family-centered testing or population-oriented screening. The deterrent to screening will not be the inability to detect disease causing mutations but the costs and attitudes of providers and the public. When tests are provided primarily to provide information about risks to future children, some people will oppose screening on religious or moral grounds. When there are no inexpensive treatments, some will fear that insurance companies and employers will use tests to deny them health care coverage. Some may not want to know their risks for disorders about which little can be done. For common, multifactorial disorders, genetic tests will have low predictive value. Because of these problems, the decision to be tested, regardless of the destination, requires that "testees" be fully informed and consent to testing. When acceptance rates are low, screening is less likely to be cost-effective; family-centered testing becomes the default destination. PMID- 1634044 TI - Ethical implications of screening asymptomatic individuals. AB - There has been a long-standing consensus on the principles that should guide screening asymptomatic individuals whether for treatment, counseling, or research. Advances in molecular biology will increase the rate of new opportunities for such screening. The benefits and risks, for individuals as well as the public health, will vary with each new test. As with all new technologies, these benefits and risks will have to be assessed in well-designed and well reviewed studies if individuals are to be allowed to make informed decisions regarding whether or not to be tested. PMID- 1634045 TI - The recombinant congenic strains for analysis of multigenic traits: genetic composition. AB - The genetic control of susceptibility to many common diseases, including cancer, is multigenic both in humans and in animals. This genetic complexity has presented a major obstacle in mapping the relevant genes. As a consequence, most geneticists and molecular biologists presently focus on "single gene" diseases. To make the multigenic diseases accessible to genetic and molecular analysis, we developed a novel genetic tool, the recombinant congenic strains (RCS) in the mouse (4). The RC strains are produced by inbreeding of mice of the second backcross generation between two inbred strains, one of which serves as the "donor" and the other as the "background" strain. A series of RCS consists of approximately 20 strains, each carrying a different set of genes: approximately 12.5% genes from the common donor inbred strain, the remaining 87.5% from the common background inbred strain. As the set of donor strain genes in each RC strain is different, the nonlinked genes of the donor strain involved in the control of a multigenic trait, e.g., cancer susceptibility, become distributed into different RC strains where they can be analyzed one by one. Hence, the RCS system transforms a multigenic trait into a series of single gene traits, where each gene contributing to the multigenic control can be mapped and studied separately. Recently we demonstrated that the RCS system is indeed capable of resolving multigenic traits, which are hardly analyzable otherwise, by mapping four new colon tumor susceptibility loci (8; P. C. Groot, C. J. A. Moen, W. Dietrich, L. F. M. van Zutphen, E. S. Lander, and P. Demant, unpublished results). For successful application of the RCS system, extensive genetic characterization of the individual recombinant congenic strains is essential. In this paper we present detailed information about the genetic composition of three series of RC strains on the basis of typing of 120-180 markers distributed along all autosomes. The data indicate that the relative representation of the donor strain genes in the RC strains does not deviate from the theoretical expectation, and that the RC strains achieved a very high degree of genetic homogeneity and for all practical purposes can be considered inbred strains. The density and distribution of markers reported here permits an effective mapping of unknown genes of donor strain origin at almost all autosomal locations. Much of this information has been obtained using the new class of genetic markers, the simple sequence repeat polymorphisms.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1634046 TI - Immune tolerance to a defined heterologous antigen after intrasplenic hepatocyte transplantation: implications for gene therapy. AB - Development of a host immune response against gene products expressed by genetically modified cells could be a serious limitation for gene therapy. During examination of whether site-specific differences in antigen presentation could regulate the host immune response, we observed an absence of antibodies against hepatitis B virus surface antigen (HBsAg) when HBsAg producing transgenic hepatocytes were transplanted into the spleen. Intrasplenic transplantation resulted in translocation of a large number of cells into the portal vascular bed and liver sinusoids. In these recipients, HBsAg secreted by the transplanted hepatocytes circulated indefinitely in the blood. In contrast, subcutaneous or intraperitoneal transplantation of the transgenic hepatocytes induced an anti-HBs response, followed by clearance of serum HBsAg. Rechallenge with HBsAg in a highly immunogenic form failed to break the tolerance in intrasplenic hepatocyte recipients even though these animals responded to another antigen (keyhole limpet hemocyanin). Immunization with HBsAg in intraperitoneal recipients of HBsAg producing hepatocytes further elevated anti-HBs titers. Our results indicate that hepatocyte transplantation into the portal vascular bed via injection into the spleen can confer immune tolerance to secreted heterologous antigens. This finding should have important implications for human gene therapy as well as for analyzing the mechanisms of immune tolerance. PMID- 1634047 TI - Dynamic changes in HIV-1 quasispecies from azidothymidine (AZT)-treated patients. AB - The emergence of azidothymidine (AZT)-resistant human immunodeficiency virus (HIV) variants in clinical samples was studied by a direct genomic sequencing method. Sequential lymphocyte samples from four patients, who had been treated with AZT for up to 27 months, were shown to gradually accumulate multiple nucleotide changes, some of which are known to be associated with AZT resistance. Several samples were shown to contain mixtures of wild-type and mutated genomes, indicating gradual rather than sudden changes in the HIV-1 quasispecies. These results demonstrate for the first time that automated solid-phase DNA sequencing is a rapid and useful tool for investigation of antiviral drug resistance and suggest that DNA sequencing may be important in routine clinical diagnostics in the future. PMID- 1634048 TI - Ataxia-telangiectasia: linkage analysis of chromosome 11q22-23 markers in Turkish families. AB - To further pinpoint the location of the genes for ataxia-telangiectasia on the long arm of chromosome 11, we performed linkage analysis and analysis of recombinants of genetic haplotypes on 14 Turkish families with ataxia telangiectasia, 12 of which were consanguineous. These studies used more than 25 polymorphic genetic markers spanning a region of the long arm of chromosome 11 that is larger than 50 cM. Seven markers gave significant LOD scores to AT: CJ5, DRD2, CJ208, S144, CD3E, PBGD, and S147, as did haplotypes created with pairs of markers DRD2/CJ5 and S144/CJ208, giving recombination fractions (theta) of 0.00, 0.00, 0.05, 0.08, 0.03, 0.09, 0.07, 0.00, and 0.06, respectively. Monte Carlo analysis of these 14 Turkish families indicated the best location for a single AT gene to be within a 6 cM sex-averaged (3 cM male-specific) interval defined by STMY and CJ77; this was three times more likely than the next most likely location (peak III) at the DRD2 locus. The analysis also revealed a peak (peak II) between S147 and S133, which may represent the complementation group D gene. Recombinant analysis of haplotypes also localized an AT locus to the STMY-CJ77 interval. Taken together, these results suggest that at least two distinct AT loci exist (ATA and ATD) at 11q22-23, with perhaps a third locus, ATC, located very near to the ATA gene. This genetic heterogeneity further complicates plans to isolate the major ATA and ATC genes and to begin identifying AT carriers in the general population. PMID- 1634049 TI - Intrathymic implants of genetically modified fibroblasts. AB - Implantation of autologous rodent fibroblasts genetically altered to express human growth hormone has recently been shown to be a feasible approach to the delivery of new gene products in somatic gene therapy. However, the novel gene product elicited in its recipients an intense antibody response that would have curtailed the effectiveness of such therapy. The possibility of inducing tolerance to foreign gene product was explored by implanting allogeneic fibroblasts transfected with the human growth hormone gene into rat thymus, a site recently shown to be immunologically privileged and able to induce donor specific tolerance to transplanted tissues. In the circulation of the implanted rats, human growth hormone was detected at 4-15 ng/ml serum within the first day and subsided to 0.6-9 ng/ml within the first wk in all animals implanted either thymically or intraperitoneally. Within 2-3 wk, high titers of anti-human growth hormone were detected in all animals regardless of the site of implantation. The failure of the thymus to offer immune protection for the foreign antigen was further confirmed when the animals were subsequently challenged with purified human growth hormone. An immediate twofold increase in titer within the first week of challenge was detected in animals previously implanted thymically. In contrast, animals implanted intraperitoneally but treated with short-term daily injection of cyclosporine A (28-41 days) did not mount any significant antibody response to human growth hormone throughout the experiment or even when challenged subsequently at weeks 8-10 with purified growth hormone. In conclusion, implantation of genetically modified fibroblasts in the thymus does not lead to tolerization toward soluble novel gene product secreted by these cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634050 TI - Mechanisms of inherited deficiencies of multiple UDP-glucuronosyltransferase isoforms in two patients with Crigler-Najjar syndrome, type I. AB - Crigler-Najjar syndrome, type I (CN-I) is a potentially lethal disorder characterized by severe unconjugated hyperbilirubinemia resulting from a recessively inherited deficiency of hepatic UDP-glucuronosyl-transferase (UGT) activity toward bilirubin (B-UGT). Two forms of B-UGT exist in human liver. mRNAs for these two forms and that for another isoform with activity toward simple phenols (P-UGT) have unique 5' regions, but their 3' regions are identical. The three mRNA species are derived from a single locus; the unique 5' regions are encoded by single unique exons and the identical 3' regions consist of four consecutive exons that are shared by all three isoforms. In this paper, we determined genetic lesions in two CN-I patients with deficiency of hepatic B-UGT and P-UGT activities. In one patient, there was a C----T substitution in exon 4 (common region) predicting the substitution of a serine residue with a phenylalanine residue; this mutation was present in the identical region of B-UGT and P-UGT mRNAs. In the other patient, a C----T substitution in exon 2 (common region) of the B-UGT/P-UGT locus resulted in a premature stop codon. This exon (132 nt) was absent in heptic B-UGT and P-UGT mRNAs of this patient due to exon skipping during pre-mRNA processing. Sequence abnormality of three distinct mRNA species explains the abnormality of multiple UGT isoforms in these patients. Presence of identical abnormalities in the common regions of the three mRNAs is consistent with the finding that the common 3' regions of the two B-UGT mRNAs and the P-UGT mRNA are encoded by four shared exons. PMID- 1634051 TI - Genetics 50 years ago. PMID- 1634052 TI - On the use of color slides. PMID- 1634053 TI - Effects of radiation on humans during prolonged spaceflight. PMID- 1634054 TI - Oral 5-aminosalicylic acid (Asacol) in the maintenance treatment of Crohn's disease. The Italian IBD Study Group. AB - A randomized, placebo-controlled multicenter trial was conducted to evaluate the efficacy and safety of a delayed-release formulation of 5-aminosalicylic acid (5 ASA) (Asacol; Giuliani & Bracco, Milan, Italy) for prevention of clinical relapse in 125 patients with inactive Crohn's disease. Patients in remission [Crohn's Disease Activity Index (CDAI) less than 150] between 3 months and 2 years were randomly allocated to receive either 800 mg 5-ASA three times daily (n = 64) or placebo (n = 61) for up to 12 months or until relapse of symptoms. Relapse was defined by a CDAI greater than 150, with a minimum increase of 100 points over the baseline value. The cumulative relapse rates were 12% in the 5-ASA group and 22% in the placebo group at 3 months [95% confidence interval (CI) for the difference, -4 to 24]; 28% and 41%, respectively, at 6 months (95% CI, -4 to 30); and 34% and 55%, respectively, at 12 months (95% CI, 3-39; P = 0.02, log rank test). Significant decrease in the risk of relapse was found in patients with ileitis, in those with previous bowel resection and, in those with prolonged prestudy remission. Eight patients (5 on 5-ASA, 3 on placebo) withdrew from the study because of adverse reactions, but no major clinical or laboratory adverse effect was observed. It is concluded that oral 5-ASA coated with Eudragit S (Rohn Pharma GmbH, Wieterstadt, Germany), 2.4 g daily, is safe and seems superior to placebo in preventing or delaying clinical relapse in Crohn's disease, especially in milder cases and in ileal disease. PMID- 1634055 TI - Measurement of gastric emptying by magnetic resonance imaging in humans. AB - A new noninvasive radiation-free method to measure gastric emptying in humans was developed. The upper abdomen was recorded with a magnetic resonance imager after administration of a liquid meal containing Gadolinium tetraazacyclododecane tetraacetic acid as a magnetic resonance image (MRI) marker. Meal volumes, total gastric volumes, and secretory rates were measured. The MRI technique was validated simultaneously by the double indicator method in 5 healthy volunteers and in 5 patients with symptoms of disordered gastric emptying applying gamma camera scintigraphy and MRI in randomized order. Similar gastric meal emptying curves were obtained in volunteers and in patients by MRI and the reference methods as assessed by linear (r greater than 0.90; P less than 0.001) and intraclass correlation analysis (r greater than 0.905) for T1/2, areas under the curve, and percent of gastric meal retained. Furthermore, similar total gastric volumes and gastric secretory rates were measured by MRI and the double indicator technique. The new MRI method correctly reflected gastric emptying disorders in patients. Thus for the first time it is possible to combine these measurements of gastric functions in a single method and to relate them to gastric morphology visualized by the generation of three-dimensional images. PMID- 1634056 TI - The effect of vasoactive intestinal polypeptide on the lower esophageal sphincter in achalasia. AB - Vasoactive intestinal polypeptide (VIP) is one of the main neurotransmitters implicated in the relaxation of the lower esophageal sphincter (LES). The effect of exogenous VIP on LES motor activity was determined by esophageal manometry. LES pressure (LESP) and LES relaxation were compared in four healthy volunteers and in six patients with achalasia. The effects of intravenous doses of 1.5, 3, and 5 pmol.kg-1.min-1 of VIP were compared with placebo. Neither placebo nor 3 and 5 pmol.kg-1.min-1 of VIP produced any effect on esophageal motility in healthy volunteers. In achalasia the three doses of VIP caused a dose-dependent decrease in LESP with a significant improvement in LES relaxation. A dose of 5 pmol.kg-1.min-1 produced a maximal decrease of 51% in LESP. A beta-adrenergic agonist, isoproterenol, caused a decrease in LESP both in healthy volunteers and in patients with achalasia without improving LES relaxation. In summary, intravenous VIP improved LES relaxation and caused a decrease in LESP in patients with achalasia without affecting LESP in healthy volunteers, indicating that the LES muscle in achalasia is supersensitive to VIP. The current study suggests that a selective damage in the noncholinergic nonadrenergic innervation of the esophagus is in part responsible for the motor alteration seen in these patients. The findings and the inability of isoproterenol to improve LES relaxation despite decreasing LESP support a role in VIP as a indicator of LES relaxation. PMID- 1634057 TI - Cephalic stimulation of gastrointestinal secretory and motor responses in humans. AB - The present study was designed (a) to investigate the cephalic phase of gastropancreatic secretion, antroduodenal motility, and regulatory peptide release in six healthy young men and (b) to assess its regulation by the cholinergic system and endogenous cholecystokinin. Sham feeding performed for 15 minutes induced a concurrent stimulation of gastropancreatic secretion, antroduodenal motility, and pancreatic polypeptide release that lasted for 30 minutes. Reappearance of interdigestive phases III was retarded in the post-sham fed state. Atropine abolished secretory, motor, and pancreatic polypeptide responses to sham feeding and enhanced gastrin release. The cholecystokinin receptor antagonist loxiglumide did not attenuate pancreatic enzyme response but diminished antral motor response by 72% (P less than 0.05) and release of pancreatic polypeptide by 91% (P less than 0.05); it enhanced gastrin release and abolished retardation of reappearance of phase III with sham feeding. It is concluded that (a) there is a distinct cephalic phase of gastropancreatic secretion, antroduodenal motility, and pancreatic polypeptide release in humans that is primarily under cholinergic control and that (b) endogenous cholecystokinin is involved in antral motor, gastrin, and pancreatic polypeptide responses to sham feeding. PMID- 1634058 TI - Crohn's disease in the northeastern and northern Isles of Scotland: an epidemiological review. AB - An epidemiological study of Crohn's disease has been conducted in northeastern Scotland since 1955 and in the Orkney and Shetland Islands since 1966 through the end of 1988. There were 856 verified cases on the mainland and 58 in the northern isles. There has been no change in the sex ratio on the mainland in recent years, with 63% of patients female. Younger men and women living in the city of Aberdeen are more liable to develop Crohn's disease than rural inhabitants; the reverse is true for men over 60 years of age. The annual incidence of new cases has increased; within the city of Aberdeen it was 11.6 per 100,000 during 1985-1987. The point prevalence on December 31, 1988, for northeastern Scotland was 147 per 100,000. Family histories of the disease were noted in 8.3% of cases. The disease now affects more distal parts of the intestinal tract. There is no clear correlation between these changes and variations in the environment or lifestyle of the population. In the Orkney Islands the overall incidence was 6.1 per 100,000, and there was a male preponderance. In the Shetland Islands the incidence was 5.7 per 100,000 during 1966-1988. A family history of Crohn's disease was more common in the northern islands than on the mainland. PMID- 1634059 TI - Effects of acute normovolemic anemia on gastric mucosal blood flow in rats: role of nitric oxide. AB - The present study investigates the effects of acute normovolemic anemia induced by isovolemic hemodilution on gastric mucosal blood flow (GMBF), measured by hydrogen gas clearance, and on the oxygen and hemoglobin content in the gastric mucosa, estimated by reflectance spectrophotometry. GMBF significantly increased after 3 and 6 mL of isovolemic hemodilution (from 50 +/- 5 to 70 +/- 7 and 77 +/- 6 mL.min-1.100 g-1, respectively; P less than 0.05) compared with basal values (50 +/- 5.mL-1.min-1.100 g-1; P less than 0.05). Oxygen content remained unchanged, whereas hemoglobin concentration decreased in parallel with the decrease in hematocrit. In a second set of experiments, the role of endogenous nitric oxide (NO) as a possible mediator of the gastric vascular changes induced by hemodilution was investigated by using the specific inhibitor of NO biosynthesis, NG-monomethyl-L-arginine (L-NMMA). The increase in GMBF induced by 3 mL of isovolemic hemodilution (delta 23 +/- 7 mL.min-1.100 g-1) was attenuated in a dose-related manner with L-NMMA, 6.25 mg/kg IV (delta 15 +/- 4 mL.min-1.100 g-1) or 50 mg/kg IV (delta 5 +/- 2 mL.min-1.100 g-1 g; P less than 0.05). The concurrent administration of L-arginine (the precursor of NO biosynthesis) abolished the effects of L-NMMA on GMBF changes. The current findings show that acute normovolemic anemia causes an increase in GMBF that is dependent on the endogenous formation of NO. PMID- 1634060 TI - Transient mosaic patterns of morphological and functional differentiation in the Caco-2 cell line. AB - To gain further insight on the mosaic expression of specific functional intestinal markers (such as sucrase-isomaltase) in postconfluent Caco-2 cells, a human colon cancer cell line unique in its property to differentiate in vitro into a mature enterocyte-like cell type, a comparative study was undertaken to examine the morphological and functional differentiation of Caco-2 cells at various culture stages. The observations clearly indicate that Caco-2 cells can exist only in three different states in culture: homogeneously undifferentiated (at subconfluence), heterogeneously polarized and differentiated (between 0 and 20 days after confluence), and homogeneously polarized and differentiated (after 30 days). Indeed, in the intermediate state, a strong discrepancy is found among adjacent differentiating cells throughout the monolayer relative to sucrase isomaltase expression as well as to cell morphology and brush border organization. Back-scattered electron imaging analysis showed a lack of correlation between these parameters at the cellular level. These observations indicate that morphological and functional differentiations of Caco-2 cells progress concomitantly according to a transient mosaic pattern, thus providing evidence that these two processes are not coupled. PMID- 1634061 TI - Ontogeny of procholecystokinin maturation in rat duodenum, jejunum, and ileum. AB - Expression and processing of procholecystokinin (proCCK) in rat intestine during development were examined using sequence-specific immunoassays, cleavage with processing-like enzymes, and chromatography. Fetal proCCK concentrations were similar in duodenum, jejunum, and ileum, but the maturation to CCK followed different courses: duodenal CCK increased from 14 pmol/g in the fetus to 86 pmol/g 4 days after birth and then declined to 17 pmol/g in the adult. In jejunum, CCK varied from 34 pmol/g in the fetus to 127 pmol/g at day 7, decreased to 54 pmol/g at day 21, and increased again to 93 pmol/g in the adult. Ileal CCK decreased from 20 pmol/g in the fetus to 10 pmol/g postnatally. Whereas duodenal proCCK after birth matured completely to carboxyamidated CCK, jejunoileal proCCK matured only partially. Chromatography showed an increase of tyrosine-sulfation and proteolytic processing of N-terminal sequences. At day 7 jejunal cholecystokinin octapeptide (CCK-8) constituted only a minute fraction of the carboxyamidated CCK, of which less than half was sulfated. However, in the adult jejunum, CCK-8 constituted a significant fraction, which was completely sulfated. It is concluded that the CCK gene is well expressed at propeptide level in the fetal small intestine. Postpartum maturation of proCCK, however, is late and differs in the three parts of the small intestine. The belated maturation supports the hypothesis that factors other than CCK regulate pancreatic growth in fetal and neonatal life. PMID- 1634062 TI - Surveillance in the routine management of ulcerative colitis: the predictive value of low-grade dysplasia. AB - Biopsies obtained at colonoscopy from 121 patients with ulcerative colitis (UC) for greater than 7 years were reviewed. Dysplasia or neoplasia was found in 27 patients (22%) after a mean of 16 years; 22 (18%) had dysplasia (all low grade), 2 had polyps, and 3 had carcinoma without prior dysplasia. Seven had dysplasia (or neoplasia) on the next examination, and another 4 after multiple negative examinations. Dysplasia preceded carcinoma in 4 (18%) of the 22 patients, and carcinoma occurred in 7 (6%) of 121 patients. The average time from the first encounter of dysplasia to the finding of carcinoma was 6.3 years, and 3 of 4 patients with negative second colonoscopies then had unremarkable examinations for 2-5 years. Dysplasia without cancer was found later in another 3. Dysplasia was found in 12 of 13 colectomy specimens, including the 3 from patients with cancer in whom no dysplasia had been found at surveillance colonoscopy. Active disease did not eliminate the capability to detect dysplasia or negate the value of surveillance for cancer when colonoscopy was conducted for routine clinical indications. Most dysplasia was detected in the rectum and sigmoid, supporting the value of interim sigmoidoscopies and biopsies during routine management of UC. Compliance for surveillance was diminished when the patient was asymptomatic, thereby increasing the risk of cancer. Low-grade dysplasia, like high-grade dysplasia, is predictive of future carcinoma and warrants careful follow-up. A "negative" second examination is no basis for a sense of security or relaxation of vigilance. PMID- 1634063 TI - Neutrophil autoantibodies in ulcerative colitis: familial aggregation and genetic heterogeneity. AB - The possibility that the neutrophil autoantibodies associated with ulcerative colitis represent a genetic marker of susceptibility was investigated by determining their prevalence in unaffected relatives of patients. Neutrophil autoantibodies were detected using an enzyme-linked immunosorbent assay, and positive values were confirmed by indirect immunofluorescence. An increased prevalence of neutrophil antibodies was found not only in the probands (68%, 26/38) but also in their clinically unaffected family members (15.7%, 17/108) compared with controls (2.9%, 1/35) (P less than 0.0001 and P less than 0.05, respectively). These results were confirmed with sera from a second center, where 86.4% (19/22) of probands were positive and 20.9% (9/43) of their relatives were positive. The prevalence of neutrophil autoantibodies in the relatives of probands who were antibody positive (21.4%) was significantly greater than the prevalence in relatives of probands who were antibody negative (7%; P less than 0.05). The findings are consistent with these antibodies being a potential marker of genetic susceptibility to ulcerative colitis and suggest the possibility of genetic heterogeneity within this disease. PMID- 1634064 TI - Nutrient-independent increases in proglucagon and ornithine decarboxylase messenger RNAs after jejunoileal resection. AB - To assess potential mediators of adaptive bowel growth, ileal proglucagon messenger RNA (mRNA) ornithine decarboxylase (ODC) mRNA, plasma enteroglucagons, and plasma glucagonlike peptide I (GLP-I) were analyzed in rats soon after jejunoileal resection or control transection. Analyses were performed before and after refeeding to establish whether responses are nutrient dependent. The elevation of ileal proglucagon and ODC mRNAs within 12 hours after resection and before refeeding shows a nutrient-independent component of the adaptive response. The onset of adaptive growth of the ileum required luminal nutrient but occurred very rapidly, within 4 hours of refeeding. The onset of adaptive growth was accompanied by transient elevation of ileal ODC mRNAs. Ileal proglucagon mRNA and plasma GLP-I levels were also elevated, and these increases were sustained up to 8 days after resection. These early and sustained increases in proglucagon mRNA and plasma GLP-I indicate that in addition to the enteroglucagons, other intestinal proglucagon-derived peptides must be considered as potential mediators of adaptive growth after jejunoileal resection. PMID- 1634065 TI - High-density lipoprotein 3 retroendocytosis: a new lipoprotein pathway in the enterocyte (Caco-2). AB - The present study in Caco-2 cells, derived from a human colon carcinoma and capable of enterocyte differentiation in culture, describes a retroendocytotic pathway for high-density lipoprotein 3 (HDL3). These cells exhibit specific binding of apolipoprotein E-free HDL3 which was competed for by HDL3 but not by low-density lipoproteins. At 37 degrees C, degradation was negligible and intact particles were internalized and resecreted into the medium within 2 hours. Electron microscopy showed binding and internalization of gold-labeled HDL3 in coated pit regions and transport in endosomes distinct from lysosomes to lipid droplets. The fusion of these endosomes with lipid droplets was followed by their dissolution and the subsequent extrusion of HDL particles from the cells. Fluorescence labeling studies of HDL3 supported cytosolic transport in vesicles. Specific binding showed negative feedback regulation by HDL3, was modulated by alterations in cellular cholesterol content, and increased with the cellular state of differentiation. HDL3 mediated efflux of endogenously labeled cholesterol. It is concluded that intact HDL3 is bound specifically by Caco-2 cells, leading to a subsequent intracellular passage and resecretion through a process of retroendocytosis effecting the efflux of cellular cholesterol. PMID- 1634066 TI - Spectrum of injury produced in the duodenum by perfusion with luminal acid in the rat. AB - The dose and time dependence of duodenal mucosal injury by luminal acid perfusion was studied. Saline, 0.01, 0.05, 0.15, and 0.3N HCl, were perfused through the proximal duodena of rats for 5, 15, or 30 minutes and then harvested for histological examination. In a second set of studies, after a 30-minute perfusion, duodena were harvested either immediately or 2, 4, 8, or 24 hours after the perfusion to study the recovery from injury. Acid disappearance (acid delivered minus acid recovered) was measured in all groups. Duodena were examined grossly, then fixed, stained, and scored histologically. Whereas no gross mucosal injury was noted, there was graded histological injury proportional to acid concentration. Injury occurred early in the perfusion and changed little with increased perfusion durations. The initial injury lead to an acid disappearance rate that was proportional to acid concentration and, therefore, the degree of injury. After the initial injury occurred, the rate of acid neutralization was unchanged by increased duration of acid perfusion. This acid neutralization protected against further injury despite the continued presence of acid. Recovery from injury was complete with physiological (0.01 and 0.05N HCl) but not pharmacological (0.15 and 0.3N HCl) concentrations of acid. It is concluded that acid-induced duodenal injury occurs within 5 minutes of exposure, is proportional to the acid concentration, and results in acid neutralization that protects against extension of the injury with continued acid exposure. PMID- 1634067 TI - A physiological role for cholecystokinin as a regulator of gastrin secretion. AB - To explore the role of cholecystokinin (CCK) in regulating gastrin secretion in humans, the effect of a CCK antagonist (loxiglumide) on meal-stimulated hormone responses was investigated. Subjects received 500 mL of a liquid test meal in the presence and absence of loxiglumide (22 mumol.kg-1.h-1). In the control experiments, both plasma gastrin and CCK levels increased postprandially. In loxiglumide-treated subjects there was a marked elevation in gastrin (area under the curve, 11,042 +/- 1493/120 min vs. 2156 +/- 281 pg/120 min) and CCK levels compared with the control experiment. These observations were confirmed in experiments with modified sham feeding and gastrin-releasing peptide stimulation in which loxiglumide pretreatment also caused a significant increase in gastrin release compared with saline (P less than 0.05). Further studies with intravenous infusion of gastrin, CCK-8, and CCK-33 with and without loxiglumide showed that the increases in CCK and gastrin during loxiglumide application cannot be explained by alterations in clearance rates. The findings of this study show that postprandial gastrin secretion is influenced by CCK and support the concept of a negative feedback control of gastrin secretion by CCK. PMID- 1634068 TI - Pathophysiology of small intestinal malabsorption in gerbils infected with Giardia lamblia. AB - Mongolian gerbils were infected with a human pathogenic Giardia lamblia strain and compared with sham-treated control animals 6 days after inoculation. Infection resulted in crypt hyperplasia associated with an increased enterocyte migration rate. Villus height was decreased in the duodenum, unchanged in the jejunum, and increased in the ileum of infected animals. Epithelial microvilli were markedly shortened, and brush border surface area decreased in the jejunum and ileum of infected animals. Thymidine kinase activity was increased in isolated duodenal villus enterocytes but did not differ in the jejunum and ileum. In vitro and in vivo experiments showed that the infection resulted in decreased jejunal glucose-stimulated electrolyte, water, and 3-O-methyl-D-glucose absorption, whereas in the ileum in vitro electrolyte and 3-O-methyl-D-glucose absorption was similar in infected and control animals. Thus, in the jejunum infection causes electrolyte, solute, and fluid malabsorption associated with decreased brush border surface area. The results indicate that the diarrhea associated with giardiasis is caused by malabsorption rather than active secretion. PMID- 1634069 TI - Familial aggregation of inflammatory bowel disease in northern Italy: a multicenter study. The Gruppo di Studio per le Malattie Infiammatorie Intestinali (IBD Study Group). AB - To assess the familial aggregation of inflammatory bowel disease (IBD) in Italy, the family pedigrees of 411 patients with ulcerative colitis (UC) and 241 patients with Crohn's disease (CD) seen at 14 participating hospitals were studied. Sufficient information was obtained on 97% of 3752 first-degree relatives, 80% of 8869 second-degree relatives, and 74% of 5791 cousins. Thirty six propositi (5.52%) had a total of 44 affected relatives (16 CD, 28 UC). The prevalence of IBD was higher in first- than in second-degree relatives and cousins (791, 112, and 163 in 100,000, respectively). A strong intrafamilial disease concordance was observed, with 26 cases of UC and 6 of CD among relatives of UC patients and 10 cases of CD and 2 of UC among relatives of CD patients. The prevalence of UC among first-degree relatives of UC patients and that of CD among first-degree relatives of CD patients was 680 and 531 in 100,000, respectively. In conclusion, there is a high degree of familial aggregation for IBD in Italy, with a strong intrafamilial disease concordance. PMID- 1634070 TI - Oral immunization against cholera toxin with a live Yersinia enterocolitica carrier in mice. AB - The 70-kb pYV plasmid of Yersinia enterocolitica directs the synthesis and secretion of several virulence determinants called Yops. These proteins are produced during the invasion of the host tissues and induce a strong antibody response. The yop genes are transcribed from strong promoters activated by a common transcription activator. Recombinant Y. enterocolitica strains expressing the B subunit of the cholera toxin were constructed from a yopH-ctxB operon fusion. Integration of the gene ctxB in the pYV plasmid itself, by a double crossing over, ensured its stability in the infecting bacteria. Oral inoculation of recombinant bacteria in mice elicited serum and intestinal antibody responses and resulted in protection of the immunized mice against a cholera toxin challenge. Secretory immunoglobulin A antibodies against the cholera toxin B subunit occurred not only in the intestines but also in the respiratory tract. PMID- 1634071 TI - Lysozyme gene expression in inflammatory bowel disease. AB - Riboprobe in situ hybridization (rISH) demonstrates active lysozyme synthesis in ulcerative colitis and Crohn's disease. Maximal labeling was seen in Paneth cells, macrophages, and granulomas. Diffuse infiltration of the mucosa by lysozyme-rich polymorphs characterizes ulcerative colitis but obscures reactivity in other cell lineages in immunohistochemical studies; lysozyme mRNA is not detected in polymorphs, rISH giving a clearer picture than immunohistochemical studies of the active synthesis of lysozyme within the gut in inflammatory bowel disease. In ulcerative colitis, strong signals localized to Paneth cell metaplasia were found in 11 of 20 cases and to a lesser degree in non-Paneth cell lineages in regenerative mucosa in 13 of 20 cases. In Crohn's disease, abundant labeling was seen in tuberculoid granulomas (5 of 20) and over macrophage aggregates in the lamina propria in another 7, characteristic patterns not encountered in ulcerative colitis. Low levels of lysozyme messenger RNA were found in the ulceration-associated cell lineage ("pseudopyloric metaplasia"). These results support the view that neutrophils are largely responsible for elevated fecal lysozyme levels in ulcerative colitis and macrophages for elevated serum lysozyme levels in Crohn's disease. PMID- 1634073 TI - Bile composition, microspheroliths, antinucleating activity, and gallstone calcification. AB - This study examined if abnormalities in bile composition and antinucleating activity are associated with gallstone calcification. Nineteen controls without gallbladder disease and 42 patients with cholesterol stones were studied. Bile was obtained at surgery and analyzed for pH and PCO2, ionized calcium, and total calcium. The pH and carbonate concentrations of gallbladder bile were significantly higher in patients with calcified stones than in patients with noncalcified stones and in controls, resulting in significantly higher levels of the ion product in patients with calcified gallstones. Microspheroliths of calcium carbonate, seen on microscopic examination of bile, predicted stone calcification with a sensitivity of 86%, a specificity of 86%, and a predictive value of 86%. Bile from control subjects completely inhibited precipitation of calcium carbonate from a supersaturated solution, whereas bile from subjects with calcified and noncalcified gallstones did not. It is concluded that gallstone calcification is related to elevated bile pH and carbonate concentrations, resulting in an elevated ion production of calcium carbonate in gallbladder bile. In addition, bile from subjects with calcified and noncalcified gallstones lacks antinucleating activity for calcium carbonate. PMID- 1634072 TI - Fecal osmotic gap and pH in experimental diarrhea of various causes. AB - Although the osmotic gap of fecal fluid is often used to distinguish osmotic diarrhea from secretory diarrhea, there has never been a scientific evaluation of the validity of this concept. Similarly, although a low fecal fluid pH value is used to indicate that diarrhea is mediated by carbohydrate malabsorption, the validity of this method is unproven. Therefore, in the present study, diarrhea was induced in normal subjects by different mechanisms and fecal fluid osmotic gap (using an assumed fecal fluid osmolality of 290 mOsm/kg) and pH were measured. In secretory diarrhea caused by phenolphthalein, the osmotic gap was always less than 50 mOsm/kg, whereas in osmotic diarrhea caused by polyethylene glycol, magnesium hydroxide, lactulose, and sorbitol, the osmotic gap always exceeded 50 mOsm/kg. In osmotic diarrhea caused by sodium sulfate, the fecal fluid osmotic gap was less than 50 mOsm/kg, but phenolphthalein-induced secretory diarrhea could be distinguished from sodium sulfate-induced osmotic diarrhea by the fecal chloride concentration. When diarrhea was caused by carbohydrate malabsorption (lactulose or sorbitol), the fecal fluid pH was always less than 5.6 and usually less than 5.3; by contrast, other causes of diarrhea rarely caused a fecal pH as low as 5.6 and never caused a pH less than 5.3. It is concluded that measurement of fecal fluid osmotic gap and pH can distinguish various mechanisms of experimental diarrhea in normal subjects. The concepts on which these tests are based are therefore verified experimentally. PMID- 1634074 TI - Pancreatic and hepatic abscesses: a late complication in 10 patients with chronic pancreatitis. AB - In this prospective long-term study of chronic pancreatitis (n = 336) over the last 3 decades, 10 patients with advanced calcific pancreatitis developed a sepsis associated with intra-abdominal abscesses (6 pancreatic, 4 hepatic). None of the known precipitating factors were present (e.g., no pancreatic necrosis or recent surgical/endoscopic interventions, no evidence of cholangitis). Nine of 10 patients had alcoholic chronic pancreatitis. Interestingly a pancreatojejunostomy in 9 of 10 patients had been performed up to 12 years previously. Cultures from abscess aspirates and/or blood were polymicrobial, mainly a mixed enteric flora in 8 patients. All patients recovered after an appropriate antibiotic therapy with or without drainage procedures. The pathogenesis of "spontaneous" abscess formation in advanced chronic pancreatitis and its relationship to pancreatojejunostomy remain to be established. PMID- 1634075 TI - The sequence of biliary events preceding the formation of gallstones in humans. AB - The aim of the present study was to determine the sequence of events leading to formation of gallstones among obese patients predisposed to cholesterol gallstones by a very low-calorie diet. Nine obese patients beginning a 520-kcal diet had gallbladder bile collected from the duodenum before beginning the diet and seven times during the first 56 days of the diet. Biliary cholesterol saturation index and levels of arachidonate, prostaglandin E2, and glycoprotein increased significantly; nucleation time decreased; and total lipid concentration did not change. Decreases in nucleation time preceded the appearance of cholesterol crystals. Significant (P less than 0.05) increases in prostaglandin E2 level were preceded by significant increases in arachidonate level and followed by significant increases in glycoprotein level. These observations support the hypotheses that in obese patients predisposed to gallstones by very low-calorie diets (a) decreases in nucleation time are necessary before cholesterol crystals form in the gallbladder; (b) biliary arachidonate, through its conversion to prostaglandins, promotes biliary synthesis and secretion of glycoprotein; (c) biliary glycoprotein promotes nucleation; and (d) increases in the concentration of gallbladder bile are not necessary for cholesterol nucleation to occur in vivo. PMID- 1634076 TI - In vivo differences between the turnover rates of leucine and leucine's ketoacid in stable cirrhosis. AB - Based on urinary nitrogen excretion, previous studies have indicated increased protein breakdown rates in cirrhosis. However, studies using [1-13C]-leucine infusion methodology have found normal protein breakdown rates. Because abnormal partitioning between extracellular and intracellular leucine exists in cirrhosis, plasma enrichment of leucine's keto acid (KIC), a marker of intracellular leucine, may more accurately reflect protein metabolism than plasma [1 13C]leucine enrichment. Therefore, protein breakdown and oxidation were calculated using both [1-13C]leucine and [1-13C]KIC and compared with urinary nitrogen excretion in seven cirrhotics and seven matched controls after an overnight fast. The ratio of KIC and leucine plasma enrichment was decreased (P less than 0.001) in cirrhosis because of lower KIC enrichment (P less than 0.006). Cirrhotics had increased rates of protein breakdown (P less than 0.006) and protein oxidation (P less than 0.05) based on KIC (P less than 0.006) but not leucine enrichment. In controls, protein oxidation calculated from urinary nitrogen excretion did not differ from KIC results (0.88 +/- 0.08 vs. 0.83 +/- 0.06) but was higher than the leucine method (0.88 +/- 0.08 vs. 0.73 +/- 0.05; P less than 0.01). However, in cirrhotics protein oxidation based on urinary nitrogen was lower than the KIC methodology (P less than 0.01). Therefore, cirrhotics have accelerated rates of protein breakdown and oxidation associated with increased extrarenal nitrogen loss. Furthermore, these results suggest abnormal leucine transport across cell membranes. PMID- 1634077 TI - Reversibility of secondary biliary fibrosis by biliodigestive anastomosis in the rat. AB - Biliary cirrhosis with portal hypertension and hepatocellular failure is a well known complication of extrahepatic obstruction. It is unclear to what extent these changes are reversible by biliodigestive anastomosis. Therefore a rat model of relief of biliary obstruction was developed by performing Roux-en-Y choledochojejunostomy in rats after bile duct obstruction. Patency of the biliodigestive anastomosis was documented by biliary scintigraphy. Microsomal function was assessed in vivo by the aminopyrine breath test and portal hypertension by spleen pulp pressure. Microsomal function was markedly impaired in obstructed animals but recovered after biliodigestive anastomosis. Microsomal cytochrome P450 content paralleled these changes. Similarly, portal hypertension was reversed after successful relief of obstruction. Stereologic analysis showed that biliodigestive anastomosis partially reversed bile ductular proliferation and fibrosis. Studying the time course of recovery showed that restoration of microsomal function was achieved after 2 weeks whereas recovery from portal hypertension required 4 weeks of biliary drainage. Recovery of microsomal function was paralleled by normalization of microsomal lipid composition while resolution of portal hypertension occurred parallel to resolution of the histologic abnormalities. PMID- 1634078 TI - Endogenous opioids accumulate in plasma in a rat model of acute cholestasis. AB - To obtain data on the degree to which the opioid system is changed in cholestasis, endogenous opioid activity in plasma of rats with acute cholestasis was determined 5 days after bile duct resection. Total plasma opioid activity was determined using a radioreceptor technique that measured the displacement of the opiate receptor ligand [3H]-DAMGO from lysed synaptosomal fractions of normal rat brain. Plasma total opioid activity was threefold greater in bile duct-resected rats than in sham-operated and unoperated controls (P less than or equal to 0.05). Plasma levels of the individual endogenous opioid, methionine-enkephalin, were determined using a sensitive radioimmunoassay, and the specificity of the assay was confirmed using high-performance liquid chromatography. In cholestatic rats, plasma methionine-enkephalin levels were more than six-fold greater than in sham-operated controls (P less than or equal to 0.001) and more than 17-fold greater than in unoperated controls (P less than or equal to 0.001). However, plasma methionine-enkephalin levels accounted for less than 5% of total plasma opioid activity after bile duct resection. Plasma methionine-enkephalin levels in both cholestatic plasma and plasma from sham-operated animals were stable when incubated in vitro despite the presence of undiminished activity of the major enkephalin-degrading enzymes. Thus, protection of methionine-enkephalin from degradation may be a factor contributing to the elevated plasma levels of methionine-enkephalin found in cholestasis. The magnitude of the increase in plasma endogenous opioid activity in bile duct-resected rats provides support for the hypothesis that endogenous opioids contribute to the pathophysiology of cholestasis. PMID- 1634079 TI - Ileal resection/dysfunction in childhood predisposes to lithogenic bile only after puberty. AB - Children with ileal resection/dysfunction since infancy have bile that is not supersaturated with cholesterol. Five sexually mature subjects (age 16-19 years) who had been previously investigated in childhood (age 4-9 years) were studied. Gallstones were found in one. Bile rich duodenal aspirates were analyzed for lipid content (molar fraction) and the cholesterol saturation index was calculated. In the postpubertal subjects, a significantly higher proportion of biliary cholesterol (22.0% +/- 4.8% vs. 3.2% +/- 0.6% and 5.7% +/- 0.5%, P less than 0.005) and significantly lower bile acids (58.1% +/- 3.9% vs. 79.7% +/- 2.3% and 78.2% +/- 1.9%, P less than 0.005) were found compared with the initial (prepubertal) samples or in samples from 20 healthy young adults. The cholesterol saturation index was significantly higher (3.1 +/- 0.7 vs. 0.6 +/- 0.1 and 1.1 +/ 0.1, P less than 0.005) whereas phospholipid content did not change (19.9% +/- 1.6% vs. 17.1% +/- 1.8% and 16.6% +/- 1.6%) as compared with themselves before puberty and as healthy young adults, respectively. It was concluded that children with ileal resection/dysfunction do not appear at risk for cholesterol cholelithiasis before puberty; however, the development of biliary cholesterol supersaturation after puberty may predispose them to gallstone formation in adulthood. PMID- 1634080 TI - Pancreatic blood flow in cats with chronic pancreatitis. AB - Pancreatic blood flow and its relationship to pancreatic interstitial pressure were investigated in a model of chronic pancreatitis in cats using a hydrogen gas clearance technique with an intraductal electrode. The intraductal technique correlated well with blood flow measurements made using gamma-labeled microspheres (r = 0.88, P less than 0.001). In control cats, the basal blood flow of 69.1 +/- 9.5 mL.min-1.100 g-1 increased by 25% to 86.2 +/- 11 mL.min-1.100 g-1 with secretory stimulation (P less than 0.05). Interstitial pressure was -0.02 +/ 0.3 mm Hg and did not change significantly with stimulation. In cats with chronic pancreatitis, basal interstitial pressure was 1.8 +/- 0.5 mm Hg and basal blood flow 39.9 +/- 4 mL.min-1.100 g-1 (P less than 0.05). Stimulation of the chronic pancreatitis gland increased the pressure to 3.0 +/- 0.4 mm Hg (P less than 0.01) and reduced flow 15% to 34.2 +/- 4 mL.min-1.100 g-1 (P less than 0.05). Papaverine increased blood flow in control and chronic pancreatitis cats without altering tissue pressure, suggesting that despite the reduced basal blood flow, the ability to increase blood flow was preserved in chronic pancreatitis. The increased interstitial pressure associated with secretion appeared to limit the gland's normal hyperemic response in this model of chronic pancreatitis. PMID- 1634081 TI - The effect of diet on feces and jaundice during the first 3 weeks of life. AB - This study examined the relationship between fecal output and neonatal jaundice in infants exclusively fed either human milk or one of three infant formulas (whey predominant, Enfamil; casein predominant, 3305H; and casein hydrolysate, Nutramigen; all from Mead Johnson, Evansville, IN). Stool output was quantitated during the first 3 weeks of life. Jaundice was assessed by measuring serum bilirubin level and transcutaneous jaundice index. In general, after the fourth day, breast-fed infants produced lower-weight individual wet and dry stools than formula-fed infants. Cumulative wet and dry stool output was also lowest in the breast-fed infants during this time. After the first week, breast-fed infants had a higher stooling frequency than formula-fed infants. The jaundice indexes of the four groups differed significantly on all days after day 3, with highest levels in breast-fed infants and lowest levels, for unknown reasons, in those fed casein hydrolysate. The jaundice index of those fed casein hydrolysate was significantly lower than that of the other formula-fed infants on days 10-18. In the breast-fed group the decrease from day 3 to day 21 in both serum bilirubin level and the jaundice index was positively correlated with both the 21-day total wet and total dry cumulative stool weights. It is concluded that the quantity of stool excreted is related to decreases in serum bilirubin levels in infants fed human milk. PMID- 1634082 TI - Pyostomatitis vegetans and primary sclerosing cholangitis: markers of inflammatory bowel disease. AB - The case of a 34-year-old woman with both pyostomatitis vegetans and primary sclerosing cholangitis is reported and the literature reviewed. Pyostomatitis vegetans is a rare disorder characterized by friable pustules on the buccal mucosa and often peripheral blood eosinophilia. In this review, the frequent association of pyostomatitis vegetans with inflammatory bowel disease as well as the potential for pyostomatitis vegetans to present with sclerosing cholangitis and liver disease before any other manifestations of inflammatory bowel disease is discussed. Patients with pyostomatitis vegetans may need long-term care for gastroenterological disease in addition to treatment for oral lesions. PMID- 1634083 TI - Successful treatment of a hepatic cyst by one-shot instillation of minocycline chloride. AB - Hepatic cysts are not rare but usually are asymptomatic; however, large ones sometimes show clinical manifestations. Treatment of a solitary hepatic cyst by one-shot instillation of minocycline chloride is reported here; 500 mg of minocycline chloride was instilled into the hepatic cyst, 11 cm in diameter, through a percutaneous transhepatic cholangiography needle under ultrasound guidance. After 5 weeks, the cyst had decreased in size to 5 cm. Five months later, the cyst could not be detected by diagnostic imaging. Fifteen months after the treatment, no reaccumulated fluid was observed. Ultrasound-guided percutaneous one-shot instillation of minocycline chloride seems to be a safe, easy, and useful procedure for treating a hepatic cyst. PMID- 1634084 TI - Benign cartilaginous tumor (chondroma) of the liver. AB - A 44-year-old woman with a large benign cartilaginous tumor (chondroma) of the liver is presented. After being followed up by computed tomography for 6 years and with imagining evidence for a recent increase in its size, this asymptomatic tumor was successfully removed at surgery. The resected tumor proved to be chondroma, a benign cartilaginous tumor. A review of the literature showed no previous reports of this type of hepatic neoplasm. PMID- 1634085 TI - The epidemiology of inflammatory bowel disease: are we learning anything new? PMID- 1634086 TI - Oral carrier vaccines: new tricks in an old trade. PMID- 1634087 TI - The gastroenterologist's osmotic gap: fact or fiction? PMID- 1634088 TI - How does cholecystokinin contract the gallbladder? PMID- 1634089 TI - When all the pressure and squeeze backfires. PMID- 1634090 TI - Mechanisms of inflammatory diarrhea. PMID- 1634091 TI - [A new procedure for continuous measurement of fetal oxygen saturation sub partu]. AB - The principal aim of foetal monitoring during labor is early detection of hypoxia. Current methods are unable to accomplish this task. Pulse oximetry permits continuous measurement of oxygen saturation and is the best method to detect early hypoxia. In this report, an optical scalp electrode is presented, which permits continuous monitoring of foetal oxygen saturation during labor. PMID- 1634092 TI - [Obstetric pelvimetry using nuclear magnetic resonance tomography (MRI): clinical experiences with 150 patients]. AB - Between Oct. 1987 and Oct. 1991 150 patients of the Frauenklinik Freiburg were examined by MR pelvimetry (MRI), 135 of which were "ante partum", i.e. just before delivery. The indications were: earlier operative or strongly protracted delivery, clinical suspicion of disproportion between head and pelvis, or obstetrical "problem pelvis" indicated by manual pelvic examination or ultrasonic foetometry. Previous experimental measurements with a phantom and the comparison with conventional radiograms by Guthmann and Martius of 10 patients in puerperium have shown, that the mean divergence was +/- 2 mm, the maximum divergence 5 mm. The MRI method for pelvimetry "ante partum" or in childbed, proved to be a method of high accuracy and a very good option to judge the pelvic shape, whilst being well accepted by the patients. Furthermore, it allows to determine the foetal BIP (biparietal head-diameter), to judge the pelvic soft-tissue, as well as the visualisation of the birth canal, all without any exposure to radiation. MR pelvimetry is thus part of today's clinical routine. The disadvantages are still the high costs as well as the fact, that only few centres have access to MRI equipment. Nevertheless, the pelvimetry "post partum" can be safely practised radiologically due to the very low radiation exposure. PMID- 1634093 TI - [Noninvasive function tests in the evaluation of vascular reactivity in pregnancy and pregnancy-induced hypertension]. AB - At present, there is an increasing discussion regarding the change of the prostacyclin/thromboxane ratio as an aetiological factor of pregnancy-induced hypertension (PIH). By means of videophotometric capillaroscopy in the capillaries of the nailfold, it is possible to visualise the resulting changes in the microcirculation. This method employs a special illumination microscope (magnification of the optical system x 560). Red blood cell velocity is measured under test conditions and microcirculatorical reaction capacity on ischaemic stress. Studies were conducted on healthy non-pregnant women and on healthy pregnant women as well as on patients suffering from pregnancy-induced hypertension. A markedly reduced velocity of red blood cells in patients with pregnancy-induced hypertension was seen as a sign of vasoconstriction, namely, 0.53 mm/sec. versus 0.74 mm/sec. Furthermore, these patients have a higher reactivity to ischaemic stress, probably also as a result of the already existing vasoconstriction; however, the duration of the hyperaemic phases is reduced in pregnancy-induced hypertension. By this method, an insight can be gained into microcirculation in pregnancy and in pregnancy-induced hypertension. In addition, as preliminary studies have already shown, the influence exercised by different medications on microcirculation can be assessed. PMID- 1634094 TI - [Placental protein 12 (PP 12) in pregnancy-induced hypertensive diseases]. AB - Placental protein 12 (PP12) was measured in 30 patients with hypertensive disorders of pregnancy, 10 healthy pregnant and 10 healthy nonpregnant controls. Differences in PP12-concentrations of healthy nonpregnant (median 2.0 micrograms/l, range 1.0-5.5 micrograms/l) and healthy pregnant controls (median 110 micrograms/l, range 29-280 micrograms/l), as well as between healthy nonpregnant controls and hypertensive patients (median 125 micrograms/l, range 28 420 micrograms/l) were both statistically highly significant (p less than 0.001). The comparison between healthy pregnant and hypertensive women demonstrated no statistically significant differences. In coexistent intrauterine growth retardation (median 163 micrograms/l, range 60-400 micrograms/l), higher values could be observed in some patients, but this group showed no statistically significant difference compared to healthy pregnant controls with adequate fetal weight. PP12 does not seem to be a clinically usable parameter in the diagnosis of hypertensive disorders of pregnancy and fetal growth retardation, because of the widespread range of results. PMID- 1634095 TI - [B-streptococci in obstetrics--risks and consequences of maternal colonization and neonatal contamination]. AB - 2,373 mothers and their newborn were studied during two years with respect to B streptococci colonisation or contamination. Bacteriological, vaginal and anal smears were taken from mothers at the beginning of parturition, as well as the amnion and the aspirated stomach contents of the newborn, employing, in each case, conventional culture methods and a latex agglutination test as a rapid testing method. Smears from the ears were also taken from the newborn for bacteriological examination. The vertical transmission and its possible influencing variables were examined in 1,328 mother/child pairs of the first observation year. Surface contamination of the newborn was confirmed in 10% in at least one smear. In the group of mothers with B streptococci colonisation, the amnion showed the highest rate of contamination (43%), followed by the aspirated stomach contents (26%) and the ear smears (taken from each side separately) with 28% and 30% respectively. Vertical transmission was decisively influenced by vaginal maternal colonisation (50% of the cases resulting in contamination of newborn), whereas anal colonisation, if it was the only site of colonisation, resulted in contamination of newborn in only 32% of the cases. The rate of contamination of newborn dropped significantly from 50% to 20% after intrapartal antibiotic prophylaxis, the latter appearing to be meaningful only after at least 6 hours of exposure. In this group, the surface contamination could be reduced from 61% to 8%. A group of newborn suffering from early onset of sepsis (0.4%), was compared with a group of 13 newborn at risk of infection (0.9%) with established surface contamination and clinical or laboratory chemistry confirmation of infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634096 TI - [Promoting pregnancy following partial zona dissection of the oocyte within the scope of in vitro fertilization]. AB - Partial dissection of the zona pellucida (PZD) is one of several micromanipulatory methods for the treatment of male subfertility. PZD involves the mechanical introduction of a small hole in the zona pellucida of the oocyte prior to insemination. Thus, fusion with the oolemma and fertilization of the oocyte is facilitated for spermatozoa with impaired quality that otherwise would not be able to penetrate the zona. We have established this technique at our clinic and report on the first pregnancy achieved by PZD of the oocyte during our IVF programme. PMID- 1634097 TI - [Modification of in vitro motility of human sperm by various dioxin congeners in super-physiologic concentrations]. AB - Human ejaculate was fractionated using density gradient centrifugation. Highly motile spermatozoa were incubated with "superphysiological" concentrations of various dioxin congeners. Over a period of sixty hours, no relevant influence on sperm motility in comparison to control media was noted on triplicate testing. It therefore appears unlikely, that intravaginally ejaculated spermatozoa would be compromised in their motility by naturally occurring levels of dioxins in female genital tract secretions. However, this does not preclude the possibility of such dioxin levels affecting normal intratesticular spermatogenesis. PMID- 1634098 TI - [Endometrial growth in continuous, estrogen substitution monotherapy with Estraderm TTS (0.05 mg/die) in 31 postmenopausal females]. AB - To prevent hyperplasia and carcinoma of the endometrium during Estrogen Replacement Therapy (ERT), addition of progestogens once a month is considered mandatory. There is, however, no good scientific basis for this assumption. Since the addition of progestogens has several disadvantages, it is important to minimise the frequency of progestogen addition. Vaginosonography is a rather new technique, which has not yet been used for monitoring ERT. This study uses the growth of the endometrium, as it was measured by vaginosonography, as a parameter for stimulation of the endometrium by estrogens. ERT with Estraderm 50 twice a week was started in postmenopausal women. The endometrial thickness at the beginning was less than 3 millimeters. During estrogen treatment the endometrial thickness was determined every 6 to 10 weeks. As long as there was little or no increase during the estrogen treatment, no progestogen was added. Where there was a considerable growth, progestogen was added. With the use of vaginosonography, it is possible, to distinguish "fast growers" (women whose endometrium responded fast) from "slow growers". PMID- 1634099 TI - [Epidermal growth factor receptor in human breast cancer: correlation with steroid receptors, tumor stage, grading and menopausal status]. AB - In this study, correlations between the epidermal growth factor receptor (EGF-R), steroid receptors, and other prognostic parameters (grading, pTNM-status, menopausal status) were analysed in 326 primary breast carcinomas. 19% of the tumour samples were EGF-R positive, 63% were estrogen receptor (ER) and 54% progesteron receptor (PR) positive. Both steroid receptors were positive in 46% of all samples. We found a highly significant inverse correlation between EGF-R and steroid receptors. 88% of the ER positive tumours were EGF-R negative (p less than 5 x 10(-5)), 90% of the PR positive tumours were EGF-R negative (p less than 5 x 10(-5)) and 91% of the ER plus PR positive tumours were ERF-R negative (p less than 1 x 10(-6)). Grading was available in 170 cases. Six (4%) of the carcinomas were highly differentiated (G1), 82 (48%) were classified as G2, and another 82 (48%) were poorly differentiated (G3). A combination of negative ER and positive EGF-R was found more often in the population of G3 tumours. EGF-R was also positively correlated to tumour size. With regard to receptor status, we did not find a correlation with lymph node involvement. The ER correlated negatively (p less than 1.3 x 10(-5) and the EGF-R positively (p less than 0.042) with menopausal status. Thus, EGF-R overexpression seems to be a marker of morphological and functional dedifferentiation which is associated with a loss of steroid dependency and an increase of an autostimulatory-paracrine growth control. These changes seem to be related to poor prognosis. PMID- 1634100 TI - [Primary Figo stage III melanoma of the uterine cervix]. AB - Malignant melanoma of the uterine cervix is a rare neoplasm with poor prognosis. Diagnosis is confirmed by immunohistochemical methods and by exclusion of other primaries. The common treatment is radical surgery. In advanced stages, primary irradiation can be successful. We report on a case of an 83 years old patient, suffering from a malignant melanoma of the uterine cervix FIGO III AB, diagnosed by histological and immunohistochemical methods. Due to combined irradiation, complete remission of the tumour was achieved. Nevertheless, the patient died of the malignancy 15 months later. PMID- 1634101 TI - [Pregnancy onset without corpus luteum function?]. AB - Within five years, a patient had five abortions and one biochemical pregnancy with two different partners. After the fourth pregnancy, she underwent a heterologous immune stimulation. The karyotypes of all three partners were normal. On her first visit, a subclinical hypothyroidism was detected and substitution with 50 micrograms L-thyroxine was started. Before further endocrinological, virological, or anatomical investigation, the patient conceived spontaneously for the seventh time. Even though the beta-HCG-levels rose adequately and the sonographic development was according to time, serum progesterone could not be detected before the eighth week of pregnancy and sufficient levels were found from the 15th week onwards. The patient received a hormonal substitution therapy with Gravibinon 250 mg i.m. twice a week up to the 15th week of gestation. She finally delivered a 3800 g healthy boy. PMID- 1634102 TI - [Pregnancy and labor in the literature]. PMID- 1634103 TI - [Pregnancy and short-wave therapy]. PMID- 1634104 TI - Genetic and environmental effects on blood pressure in a Norwegian sample. AB - Systolic (SBP) and diastolic (DBP) blood pressures were measured in a health screening of the adult population in Nord-Trondelag, Norway. Correlations were computed for 23,936 pairs of spouses, 43,586 pairs of parent and offspring, 19,151 pairs of siblings, 1,251 pairs of grandparents-grandchildren, 1,146 pairs of biological uncles/aunts-nephews/nieces (avuncular), 801 non-biological avuncular pairs, 169 pairs of same-sex twins, and smaller groups of other types of relationships. Spouse correlations of 0.08 and 0.09 were approximately constant or slightly decreasing with marital duration. The correlation values for SBP and DBP were approximately 0.16 for parents-offspring, 0.19 to 0.23 for same sex siblings with similar values for DZ twins, 0.19 and 0.16 for opposite-sex siblings, 0.52 and 0.43 for MZ twins, and close to zero for most of the second order relationships. Genetic additive variance was estimated at 0.29 and genetic dominance variance at 0.18 with the best model for SBP. The corresponding estimates from the best models for DBP were 0.29 or lower and 0.22 or lower, the sum not exceeding 0.35. There was evidence of a moderate effect of environmental factors shared by same-sex siblings and twins (for DBP), but no cultural transmission, and whether or not adult relatives live together does not affect familial resemblance for BP. The data did not permit a very precise resolution of the relative magnitude of genetic dominance and sibling effects. The correlation structure did not show sex-specific genetic effects. PMID- 1634105 TI - Two-locus mitochondrial and nuclear gene models for mitochondrial disorders. AB - Stimulated by a large pedigree with a cochlear form of deafness, for which we considered a two-locus mitochondrial and nuclear gene model, we have extended the classic methods of segregation analysis to these classes of two-locus disorders. Based on the unique maternal transmission pattern of the mitochondria, we demonstrate that utilization of the maternal line pedigree allows us to simplify the various two-locus mitochondrial models to "one nuclear locus" models. Classifying the nuclear families into different independent groups by the mother's phenotypes allows us to estimate the nuclear gene frequency in one group and to use this estimate as the expected value to test the fitness of the model on the other group. In addition, if we restrict the analysis to specific subsets of the mating type(s), we can also test the model on specific groups of nuclear families without estimating the gene frequency. Goodness-of-fit tests can be performed on pooled sibship data as well as individual sibship data. These methods of analysis should assume increasing importance as more disorders with features of mitochondrial inheritance are identified. PMID- 1634106 TI - Adequacy of single-locus approximations for linkage analyses of oligogenic traits. AB - When a disease is controlled by two or more mendelian loci acting epistatically, it can be modeled in a linkage analysis as a single-locus mendelian disease with reduced penetrance. However, the reliability of such an approximation has not yet been demonstrated. This study evaluates the adequacy of such single-locus approximations, when the disease under investigation is determined by two loci, one of which is tightly linked to a genetic marker. A wide range of two-locus models were simulated, and analyzed under both the correct two-locus model and under a single-locus approximation to that model. In general, the single-locus approximations yielded lod scores very close to the correct ones, but estimates of theta tended to be upwardly biased. We conclude that a single-locus linkage analysis will, in general, provide an excellent approximation to a correct (two locus) linkage analysis of epistatic two-locus diseases. This enables researchers to continue to use single-locus linkage analyses when two-locus disease transmission is a possibility, and it validates linkage findings already obtained under single-locus analysis, even if the disease under investigation proves ultimately to be governed by two mendelian loci. We also examine alternative methods for obtaining parameter estimates for the single-locus approximations, and we discuss both generalizations and limitations of our findings. PMID- 1634107 TI - Detection of linkage under heterogeneity: comparison of the two-locus vs. admixture models. AB - Linkage analysis under the two-locus model and the admixture model was compared on pedigree data for a common disease stimulated under a model of genetic heterogeneity. The ascertainment of families was designed so that the samples had a large proportion of families segregating for both disease loci. The two-locus linkage analysis model did not demonstrate increased power of detecting linkage or more accurate estimates of the recombination fraction, theta than did the admixture model linkage analysis. When a sample was purposely chosen so that all of the families were segregating for both loci, then the two-locus lod score analysis was better. However, the increased power depended on assuming the correct gene frequency for the linked locus. It can be concluded that under the conditions of genetic heterogeneity examined here, testing for linkage under the admixture model is the preferred method of analysis. However, this is not a general conclusion that can apply to all two-locus disease models. PMID- 1634108 TI - Sensitivity of transmission probabilities to paternity exclusion in segregation analysis. AB - Paternity exclusions are known to be common in Western countries and are yet neglected in segregation analysis because it is almost impossible to check it systematically on a large family sample. We had the opportunity of observing the sensitivity of segregation analysis parameters to a paternity exclusion in analyzing 34 families for a simple Mendelian trait, the acetylator phenotype. We found that only one family, with proven paternity exclusion, was responsible for a strong rejection of Mendelian transmission probabilities (P much much less than 0.001). PMID- 1634109 TI - Purification and characterization of wheat alpha-gliadin synthesized in the yeast, Saccharomyces cerevisiae. AB - The development of efficient methods for production and purification of plant seed storage proteins in heterologous microbial hosts would facilitate structure function studies of these proteins. This report describes such methods applied to the production and isolation of wheat alpha-gliadin, a prolamine-type seed storage protein, from Saccharomyces cerevisiae. Beginning with the vector, growth conditions, and extraction methods of Neill et al. [Gene 55 (1987) 303-317], we implemented several improvements to increase the yields of alpha-gliadin per volume of yeast cell culture. The CYCl::Gli-A2-Y transcriptional fusion vector, pAY31 (Neill et al., 1987), was modified by replacing the ARS1 region of replication with that of the 2 mu plasmid of yeast. We formulated a new medium, a derivative of synthetic defined (SD) medium supplemented with several nitrogen sources, that allows both selection for maintenance of plasmids and growth to high cell densities. Stationary phase cultures of cells bearing the modified expression vector, and grown in this medium with glycerol and lactate as carbon sources, contain significantly higher levels of alpha-gliadin than log-phase cultures grown in SD glucose. Sonication in 80% ethanol selectively and efficiently extracts the alpha-gliadin from cell pellets of small- or large-scale cultures, allowing the purification of several hundred micrograms of the wheat protein per liter in just a few high-yield steps. The alpha-gliadin isolated from yeast elutes at the same position in HPLC as the A-gliadin fraction purified from wheat flour. N-terminal amino acid (aa) sequencing reveals that the signal peptide is removed from the gliadin precursor in yeast cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634110 TI - Expression of a synthetic gene encoding potato carboxypeptidase inhibitor using a bacterial secretion vector. AB - A synthetic gene encoding the 39-amino-acid (aa) potato carboxypeptidase inhibitor IIa (PCI-IIa) has been constructed and expressed using the secretion vector, pIN-III-ompA-3, fused in frame to the OmpA signal peptide-encoding sequence. Recombinant Escherichia coli secreted a PCI with 10 additional aa at the N terminus (rePCI + 10). These extra aa were removed by site-directed mutagenesis giving a PCI with no additional aa (rePCI), as shown by fast atom bombardment mass spectrometry (M(r) 4295). The two forms of rePCI were found almost exclusively in the culture medium, not in the periplasmic space, as would be expected from OmpA signal peptide fusions. Both rePCI + 10 and rePCI are biologically active and react strongly with serum raised against PCI from potato. A method for the purification of rePCI to homogeneity has been developed. The purified rePCI shows a Ki for carboxypeptidase A within the range of the natural PCI-IIa (1.5-2.7 nM). These results indicate that both rePCI + 10 and rePCI are properly folded and that their three disulfide bridges are correctly formed. Together with previous reports, our results show that fusion to a secretion signal peptide is an effective way of producing small proteins containing disulfide bridges in a biologically active form. PMID- 1634111 TI - Mapping of a region of dengue virus type-2 glycoprotein required for binding by a neutralizing monoclonal antibody. AB - Envelope glycoprotein E of flaviviruses is exposed at the surface of the virion, and is responsible for eliciting a neutralizing antibody (Ab) response, as well as protective immunity in the host. In this report, we describe a method for the fine mapping of a linear sequence of the E protein of dengue virus type-2 (DEN 2), recognized by a type-specific and neutralizing monoclonal Ab (mAb), 3H5. First, an Escherichia coli expression vector containing a heat-inducible lambda pL promoter was used to synthesize several truncated, and near-full length E polypeptides. Reactivities of these polypeptides with polyclonal mouse hyperimmune sera, as well as the 3H5 mAb revealed the location of the 3H5-binding site to be within a region of 166 amino acids (aa) between aa 255 and 422. For fine mapping, a series of targeted deletions were made inframe within this region using the polymerase chain reaction (PCR). The hydrophilicity pattern of this region was used as a guide to systematically delete the regions encoding the various groups of surface aa residues within the context of a near-full-length E polypeptide by using PCR. The 3H5-binding site was thus precisely mapped to a region encoding 12 aa (between aa 386 and 397). A synthetic peptide containing this sequence was able to bind to the 3H5 mAb specifically, as shown by enzyme linked immunosorbent assay. In addition, we show that rabbit Abs raised against the synthetic peptide of 12 aa were able to bind to the authentic E protein, and to neutralize DEN-2 virus in a plaque reduction assay. PMID- 1634112 TI - Functional analysis of two long terminal repeats from the HTLV-I retrovirus. AB - Human T-cell leukemia virus type I (HTLV-I) is associated with a large spectrum of clinical manifestations in man. Viral and host factors are probably involved in determining the consequences of infection. Although most of the genome of HTLV I appears remarkably stable, considerable variation is observed in the long terminal repeat (LTR) which harbors the promoter region. So far, no correlation between specific mutations and pathogenesis has been found, and the current opinion is that sequence variations reflect the geographical origin of the isolate more than the associated pathology. To assess whether the mutations observed between two HTLV-I LTRs were functionally significant, two LTRs, which differ by ten mutations, were coupled to the highly sensitive eukaryotic luciferase-encoding reporter gene, luc, and tested by transfection in a variety of cell lines. Marked differences in promoter activity were observed in some of the cells tested, whereas in other both LTRs were equally active. This result demonstrates that the minor differences observed between two HTLV-I LTRs can affect the activity level of the promoter in some cellular environments, a result which could point to the LTR as one determinant of HTLV-I cell tropism in vivo. PMID- 1634113 TI - Sodium butyrate selectively induces transcription of promoters adjacent to the MoMSV viral enhancer. AB - The long terminal repeat region of the Moloney murine sarcoma virus (MoMSV) was cloned upstream from the Chinese hamster ovary adenine phosphoribosyltransferase (APRT)-encoding gene (APRT) in order to enhance synthesis of the APRT protein. The replacement of the native promoter with the viral enhancer-promoter increased the enzymatic activity of APRT two- to threefold. Addition of sodium butyrate (NaBu) to the cell growth medium induced APRT activity ten- to 20-fold above wild type levels in both transient and stable transfectants. The introduction of the APRT native promoter between the MoMSV enhancer-promoter and structural gene reduced the magnitude of the NaBu response. The bacterial cat gene was also stimulated by NaBu when linked to the viral enhancer-promoter. No NaBu response was found in constructs lacking the MoMSV enhancer region. Northern analysis and nuclear run-on experiments indicated that NaBu enhanced transcription of APRT mRNA in both transiently and stably transfected cells, but not in cells inhibited by cycloheximide. Thus, a butyrate-response element (BRE) is associated with the MoMSV enhancer and the action of the MoMSV BRE is promoter-dependent. PMID- 1634114 TI - Expression of a gene encoding a scorpion insectotoxin peptide in yeast, bacteria and plants. AB - The nucleotide sequence encoding the scorpion insectotoxin I5A was chemically synthesized and expressed in yeast, bacteria and tobacco. The I5A peptides produced in these organisms were purified using an immunoaffinity chromatography procedure. I5A produced using the bacterial secretion system was efficiently secreted and released into the culture medium. In contrast, only a trace amount of I5A was detected in bacterial cytosols when expressed from a direct expression vector, suggesting that I5A was unstable in bacterial cells. I5A secreted from yeast using an alpha-factor signal sequence was shown to have an N-terminal (Glu Ala)2 extension, indicating incomplete processing of the secreted peptide by dipeptidyl aminopeptidase A. In tobacco, a nonsecreted form of the protein was produced. No measurable insect toxicity was observed when insect larvae were assayed, regardless of whether I5A was produced in yeast, bacteria or tobacco. The lack of toxicity is almost certainly the result of improper folding due to incorrect disulfide bond formation. The inability to produce a biologically active peptide must be overcome before scorpion toxins might be used for the genetic engineering of plants for insect resistance. The yeast and bacterial expression systems described here may be useful for further studies on the problem of expressing a biologically active peptide. PMID- 1634115 TI - Cloning and mapping of 5' exons from the gene encoding chicken beta nerve growth factor. AB - An NGF cDNA containing the 5' exons of the nerve growth factor (NGF) messenger was obtained from chicken heart mRNA using the anchored polymerase chain reaction technique. Alignment of the chicken with the corresponding murine and human sequences reveals interspecies similarities. A sequence corresponding to an exon found only in the NGF messenger, which is abundant in the submaxillary gland of the male mouse, is present in the chicken NGF cDNA. The first non-coding exons of the NGF gene are much less conserved between chicken and mouse or human than the region of the last exon encoding the mature protein. After the cloning of the chicken NGF gene from a cosmid library, the chicken NGF exons have been located within 20 kb of DNA. The chicken NGF gene is therefore shorter than its murine counterpart which spans more than 43 kb. Furthermore, the organization of the chicken and murine NGF genes markedly differs in their 5' portion. PMID- 1634116 TI - A transcriptional analysis of the gene encoding mouse U7 small nuclear RNA. AB - Expression of the U7 gene, encoding mouse U7 snRNA, following microinjection into Xenopus oocytes is both accurate and efficient, giving rise to mature U7 snRNA and a precursor with an 8-nucleotide (nt) 3' extension. The mouse U7 gene promoter, which is similar to that of the vertebrate major U genes comprising a DSE, a PSE and a 3' box, with the same spatial arrangement, is as efficient as the Xenopus U2 gene promoter in this assay. A deletion analysis of the mouse U7 gene identified sequences downstream from the 3' box, within the region (nt +74 to +196), which seem to have a negative regulatory effect upon the frequency of transcription initiation and are also required for accurate 3' end formation. Sequences in the nt -1699 to -431 region also seemed to have a negative effect on the level of transcription. In addition, sequences upstream from the PSE, within the nt -65 to -421 region, are necessary for accurate and efficient synthesis of mature U7 snRNA. Finally, the mouse U7 snRNA may not form a functional snRNP in Xenopus oocytes due to defective snRNP assembly and/or nuclear import. PMID- 1634117 TI - Basal expression of the gene (TIMP) encoding the murine tissue inhibitor of metalloproteinases is mediated through AP1- and CCAAT-binding factors. AB - In cultured murine fibroblasts, the TIMP gene (encoding tissue inhibitor of metalloproteinases) is transcribed constitutively, although at low levels. We have used a cell-free system in which nuclear extracts prepared from murine L cells support transcription from TIMP DNA templates in vitro. This system was used to study the role of cis-acting DNA sequences in the constitutive expression of TIMP. Sequences important for expression are located both 5' and 3' (in intron 1) to the major transcription start point and are required to obtain detectable levels of transcription. These regions are specifically recognized by murine nuclear factors and contain DNA motifs whose sequences closely resemble binding sites for known transcriptional activators. In particular, the data strongly suggest a role for CCAAT-binding factor(s) and AP1-binding factors in the basal transcription of TIMP. PMID- 1634118 TI - Intragenic regulatory elements contribute to transcriptional control of the neurofilament light gene. AB - To date, no DNA regions involved in the neuron-specific expression of the neurofilament light gene (NF-L) have been defined using transfection assays in cultured cells. To identify those regulatory regions in the human NF-L gene, we generated transgenic mice with a construct containing the basal NF-L promoter ( 292 to +15) fused to the cat gene and with three DNA fragments of 21.5, 7.6 and 4.9 kb each, including NF-L with different lengths of either 5'- or 3'-flanking sequences. We show that the proximal NF-L 5' region (0.3 kb) constitutes a weak promoter and that it lacks information to confer neural specificity. However, appropriate expression in the nervous system occurred when this minimal promoter was combined with either 7.3 or 4.6 kb of NF-L sequences downstream from the transcription start point. We conclude that the intragenic NF-L region contains cis-acting elements conferring cell-type-specific regulation on the basal activity of the NF-L promoter. Interestingly, AP-2 motifs were found within homologously placed introns of all three NF genes, as well as in the promoter regulatory regions of many neuronal genes. We propose that the acquisition of introns by an ancestral intronless IF gene may have contributed to the emergence of a lineage of IF genes expressed in the nervous system. PMID- 1634119 TI - Gibbon and marmoset c-myc nucleotide sequences. AB - The nucleotide sequences of the gibbon and marmoset myc loci have been determined by the dideoxy ribomethod. The number of mutations which occurred during evolution and the branches affected were deduced according to the principle of maximum parsimony, from a comparison with known mammal sequences. As previously observed for the human and chimpanzee myc genes, an Alu repeat belonging to subclass III was observed in the second intron of the gibbon myc gene. In contrast, no such element was found in the marmoset gene. Alignment of the Myc amino acid (aa) sequences provided clues for detecting which aa or which protein regions have been more heavily mutated. Conversely, some regions remained free of mutations and remained unchanged from mouse to human, most probably in connection with some important embedded property(ies). An intriguing feature of the human Myc protein is duplication of 50 aa out of 439. Strikingly, most of these aa remain unchanged in mouse, rat, cat, marmoset, gibbon, chimpanzee and human. PMID- 1634120 TI - Structures of cDNAs encoding chum salmon pituitary-specific transcription factor, Pit-1/GHF-1. AB - Pit-1/GHF-1, a POU family transcription factor, was originally isolated as a protein that contributes to the pituitary-specific expression of the mammalian growth hormone(GH)-encoding gene. Pit-1/GHF-1 has been recently implicated in the development of three types of hormone-producing cells which secrete GH, prolactin (PRL) and thyroid-stimulating hormone. A presumed pituitary hormone, somatolactin (SL) which belongs to the GH/PRL family, was previously isolated from fish. As the first step for determining the possible involvement of the Pit-1 protein in the pituitary-specific expression of the SL gene and/or in the development of SL producing cells, chum salmon Pit-1 cDNA clones were isolated. Chum salmon Pit-1 mRNAs were mainly 2 kb and 3 kb in size, and specifically expressed in the pituitaries. They encoded a 365-amino acid (aa) protein, which was 74 aa larger than that found in mammals. The identity of aa sequences between salmon and rat Pit-1 was 69%. These proteins were highly conserved in the region specific for the POU family. Salmon Pit-1 had two additional sequences each consisting of about 30 aa in the N-terminal region. The sequence involved in transcriptional activation is considered to be located in the region including the above sequences, and thus, salmon Pit-1 may possibly have novel functions distinct from those of rat Pit-1. PMID- 1634122 TI - Jimmy Connors: 'geriatric' symbol at 40. PMID- 1634121 TI - High-level secretion of the four salivary plasminogen activators from the vampire bat Desmodus rotundus by stably transfected baby hamster kidney cells. AB - The cDNAs coding for the four Desmodus rotundus salivary plasminogen activators (DSPAs) were subcloned into the mammalian expression vector, pMPSV/CMV, which carries the myeloproliferative sarcoma virus promoter and the cytomegalovirus enhancer. These constructs were transfected, together with plasmids harbouring Geneticin (G418)-resistance and puromycin-resistance genes, into baby hamster kidney cells. Through the selective pressure of both antibiotics, cell clones constitutively overexpressing the DSPA alpha 1, DSPA alpha 2, DSPA beta or DSPA gamma cDNAs were obtained. Secretion of active DSPAs was confirmed by zymographic analysis and quantified using a fibrin plate assay and ELISA. PMID- 1634123 TI - Individualizing the risk/benefit ratio of NSAIDs in older patients. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) have provided safe, effective relief of pain and inflammation in millions of elderly patients. Their role in the therapy of rheumatic disease, particularly in helping patients to maintain an independent lifestyle, is indisputable. Despite this success, recent epidemiologic studies have confirmed an increased relative risk for a wide variety of significant toxicities. Advanced age has emerged as one of the most striking risk factors for all of the commonly associated side effects. However, considering the large proportion of the population using these drugs, the absolute risk is remarkably low. Recognizing those elderly individuals most likely to benefit and least likely to suffer from NSAID use is the key to their appropriate use. PMID- 1634124 TI - Prescribing physical activity for older patients. AB - Regular exercise is an effective nonpharmacologic therapy for stress, sleep disorders, depression, and anxiety, as well as such chronic conditions of aging as hypertension, obesity, diabetes mellitus, coronary artery disease, hyperlipidemia, and constipation. Pre-exercise office assessment of cardiac risk, possible limitations, and contraindications is advised. A balanced fitness training program includes activities to increase flexibility, strength, and cardiovascular endurance. The most effective exercise prescription begins with a type of aerobic activity the patient enjoys. A prescribed schedule of stepwise increments in frequency, duration, and intensity gradually leads to a maintenance level of fitness. PMID- 1634125 TI - Deep vein thrombosis and pulmonary embolism: prevention, diagnosis, and treatment. AB - Pulmonary embolism (PE) is a significant cause of mortality in the elderly. More than 90% of pulmonary emboli originate from a thrombus in the deep veins of the legs. Proper diagnosis and treatment of deep vein thrombosis (DVT) are thus essential to prevent PE. Diagnosis of new or recurrent DVT is based on the results of one or more tests, including impedance plethysmography (IPG) or duplex venous scan; venography can often be avoided, based on results of initial testing. For suspected PE, perfusion lung scanning is the initial test of choice, followed by IPG/duplex or venography. Pulmonary angiography is indicated for patients with decreased cardiorespiratory reserve. Decisions governing prophylaxis of DVT are based on individual relative risk; prophylactic therapies include intermittent compression, low-dose heparin, and oral anticoagulants. Management of thromboembolism requires IV and oral anticoagulant therapy. PMID- 1634126 TI - Age-based rationing of medical care. PMID- 1634127 TI - Inadequate analgesia: patients endure pain, fear addiction. PMID- 1634128 TI - Ovarian dysgerminoma metastatic to the breast. AB - A 16-year-old girl underwent a right salpingo-oophorectomy for a pure dysgerminoma limited to the right ovary. One month later, she developed a right pelvic mass along with abdominal lymphadenopathies, peritoneal carcinomatosis, left breast mass, and left axillary node. Cytology of the breast mass was suggestive of a pure dysgerminoma. Breast metastases of epithelial ovarian carcinoma are uncommon. In the literature, this is the first case of a breast metastasis of an ovarian dysgerminoma. PMID- 1634129 TI - Endosalpingiosis in association with ovarian surface papillary tumor of borderline malignancy. AB - A 40-year-old woman underwent total abdominal hysterectomy, bilateral salpingo oophorectomy, pelvic/paraaortic lymphadenectomy, and omentectomy for Stage IA ovarian surface papillary tumor of borderline malignancy. Microscopic examination revealed endosalpingiosis of ovaries, the peritoneum of uterus, pelvic lymph nodes, and omentum. There was no evidence of disseminated peritoneal malignancy. The several proposed theories of the pathogenesis of endosalpingiosis are reviewed, but that involving metaplasia of the multipotential peritoneal cells is presented as the most acceptable. PMID- 1634130 TI - Immature teratoma of the ovary--an unusual case. AB - A 30-year-old female was found to have a malignant immature teratoma of the ovary 14 years ago. This was treated with surgery followed by chemotherapy. Two years later, hepatic metastasis was discovered and treated with different multiple agent chemotherapy, resulting in transformation or evolution into a mature teratoma form of disease. Twelve years later, this disease underwent malignant degeneration and transformed into a metastatic adenocarcinoma. This case report illustrates that malignant ovarian immature teratoma, teratocarcinoma, like its testicular counterpart, can evolve or differentiate into an apparently benign form of disease, but ultimately leads to death due to subsequent malignant transformation into new forms of malignancy arising from any of the three primordial germ cell layers. PMID- 1634131 TI - Cellular schwannoma of the vagina. AB - Schwannomas of the female genital tract are rare, and an example in the vagina has not previously been reported. The case of a 37-year-old woman with a cellular schwannoma of the vagina is described and is accompanied by a review of schwannomas in the female genital tract. PMID- 1634132 TI - Recurrent consecutive partial molar pregnancy. AB - Gestational trophoblastic disease (GTD) is rare. Recurrent GTD, though occurring in only 0.6-2.6% of subsequent pregnancies, has significant clinicopathological implications. These include risk of malignant sequelae and subsequent poor reproductive performance. The cytogenetics and histopathology of complete and partial moles differ, yet there are several clinicopathological similarities. Although complete hydatidiform moles are known to recur, very little is known about recurrent partial vesicular moles in world literature. We report here on a patient with four consecutive recurrent partial hydatidiform moles who is yet to achieve a normal pregnancy. Her third molar pregnancy was further complicated by severe thyrotoxicosis. The unusual histology and the progressively more aggressive clinical course are discussed. The small risk of malignant sequelae and the need for close endocrinological monitoring are highlighted, as are her chances of yet another recurrent GTD. PMID- 1634133 TI - Granulocytic sarcoma of the uterine cervix--literature review of granulocytic sarcoma of the female genital tract. AB - Granulocytic sarcoma is an extramedullary tumor of malignant granulocytic progenitor cells that accompanies, heralds, or signals relapse of acute myelogenous leukemia (AML), or indicates blastic transformation of a chronic myeloproliferative disorder. We describe a case involving the uterine cervix of a 51-year-old woman that led to the diagnosis of AML. Granulocytic sarcoma can occur in the female genital tract and may be the first clinically significant manifestation of a hematologic malignancy. The salient findings in 28 reported cases from 12 different countries are reviewed. Awareness of this lesion is important for all medical personnel involved in the health care of women. PMID- 1634134 TI - Flow-cytometric DNA analysis of stages IB and IIA cervical carcinoma. AB - The prognostic significance of flow-cytometric DNA analysis was assessed in 375 stages IB and IIA squamous cell carcinoma patients treated with radical hysterectomy and lymphadenectomy at the Mayo Clinic between 1956 and 1985. Paraffin-embedded samples containing at least 20% tumor were dewaxed, rehydrated, stained with propidium iodide, and analyzed. Among 344 assessable samples, 136 (40%) were diploid and 208 (60%) were nondiploid (26 tetraploid, 158 aneuploid, and 24 polyploid). Diploid cases were further subclassified: 25 high proliferative phase (HPP) (S+G2M greater than 20%) and 111 low proliferative phase. No significant correlation was noted between DNA diploid patterns and stage, tumor size, grade, or histotype, but HPP diploid tumors had a significantly higher risk of nodal metastasis. With a mean follow-up period of 150 months, 62 patients died of disease. No significant difference was observed in survival rates (SR) between diploid and nondiploid tumors, but the subset of HPP diploid tumors had a prognosis significantly worse than that of any other group (P less than 0.01). Other significant variables included nodal metastases, parametrial extension, age, and clinical stage. While ploidy patterns did not assign additional risk to node-positive lesions, HPP diploid tumors in node negative patients were associated with a significantly lower SR. Multivariate analyses in node-negative patients demonstrated that stage, histologic subtype, and HPP diploid patterns retained prognostic independence. PMID- 1634135 TI - Sigmoid colectomy. PMID- 1634136 TI - The combined operative and radiotherapeutic treatment (CORT) of recurrent tumors infiltrating the pelvic wall: first experience with 18 patients. AB - CORT is a new radiosurgical treatment concept for patients with recurrent gynecologic malignancies infiltrating the pelvic wall. The operative part consists of (i) staging laparotomy; (ii) maximum debulking of the tumor from the pelvic wall and exenteration of infiltrated central pelvic organs; (iii) implantation of brachytherapy guiding tubes on the residual tumor/tumor bed at the pelvic wall; (iv) pelvic wall plasty with muscle and omentum flaps to create a protective distance between the tubes and the pelvic hollow organs and to induce therapeutic angiogenesis; and (v) surgical reconstruction of bowel, bladder, and vulvoperineovaginal functions. Radiation is given postoperatively as fractionated HDR brachytherapy via the implanted tubes. Patients without prior pelvic radiation also receive preoperative whole pelvis teletherapy. Eighteen patients with recurrent malignancies infiltrating one pelvic wall have been treated with CORT in a prospective phase I/II trial at the University of Mainz. Fourteen patients had a history of radiation therapy with midpelvic doses of 40 100 Gy (median, 65 Gy) as primary treatment. Eleven patients (61%) are without evidence of disease at 6-32 months (median, 15 months) follow-up. Four patients have died from pelvic progression and distant metastases, and two patients are alive with disease after 12 months. There was no operative mortality; however, one patient succumbed from fatal thromboembolism 6 months after therapy. Three patients with prior radiation of greater than 75 Gy had to be treated for intestinal fistulas. We conclude that CORT is feasible with encouraging preliminary results. PMID- 1634137 TI - The prognostic implications of low serum CA 125 levels prior to the second-look operation for stage III and IV epithelial ovarian cancer. AB - Second-look laparotomy is performed to evaluate response to chemotherapy and to determine the need for additional treatment. The relationship between absolute levels of serum CA 125 less than 35 u/ml and disease status at second-look operation was evaluated in 95 patients with advanced-stage epithelial ovarian cancer. Eighty-six patients had Stage III disease and nine patients had Stage IV cancer. Residual tumor was documented at second-look laparotomy in 52 (55%) of the patients studied. Forty-nine percent of the 82 patients with serum CA 125 values less than 20 u/ml had residual disease. In contrast, 12 of 13 (92%) patients with serum CA 125 values of 20-35 u/ml had residual tumor at second-look laparotomy. All patients with serous cystadenocarcinomas and serum CA 125 values of 20-35 u/ml had residual tumor, and two-thirds of these cases had grossly visible disease. The positive predictive value of a serum CA 125 level of 20-35 u/ml was 0.92. These data suggest that second-look laparotomy should be deferred in patients with advanced-stage ovarian cancer until serum CA 125 values are less than 20 u/ml. PMID- 1634138 TI - Prospective histopathologic malignancy grading to indicate the degree of postoperative treatment in early cervical carcinomas. AB - During a 9-year period, 92 women with squamous cell carcinoma of the cervix, FIGO stages IA1-IIA, were subjected to primary surgery according to Wertheim Meigs. Grading according to a malignancy grading score (MGS) and evaluation of tumor size before surgery together with surgical findings of positive nodes or insufficient surgical margin at the primary site were used to identify persons prospectively at high risk for relapse. Twenty-five women thus received postoperative treatment. Results among node-positive patients were good; only 2 out of 12 patients relapsed. Among 67 node-negative patients in stages IA2-IIA, 4 relapses occurred. These 4 patients had greater than or equal to 16 risk points according to MGS, but small tumors. Instead of tumor size, supplementary risk factor is therefore needed. Among the few patients in stage IA1, no high-point patients relapsed. These patients would probably have done just as well with less extensive surgery. PMID- 1634139 TI - The role of appendectomy in surgical procedures for ovarian cancer. AB - To assess the role of appendectomy in the surgical procedures for ovarian cancer, we evaluated retrospectively the clinical charts of 435 patients who underwent surgery after diagnosis of ovarian cancer. The appendix was removed in 160 cases and pathological examination revealed 37 with metastatic implants (23%). All the patients with appendiceal metastases showed advanced disease (stages III-IV) with an incidence of 43%. Ninety-one percent (31/34) of the tumors with appendiceal involvement at the staging operation were of the serous cell type and grade II or III. No case with early stage, right ovary carcinoma showed appendiceal metastatic foci, denying the existence of a preferential lymphatic pathway. Microscopic involvement was found only in 4 patients with advanced disease (11.7%). No intra- or postoperative complication directly related to the appendectomy was recorded. We conclude, with these results, that appendectomy should be part of the cytoreductive operation for ovarian cancer. PMID- 1634140 TI - ras oncogene product p21 expression and prognosis of human ovarian tumors. AB - Monoclonal antibody rp-28 directed against the ras gene product p21 has been studied to evaluate ras p21 expression in malignant and benign ovarian tissues. Some ovarian carcinomas of serous and mucinous cystadenocarcinomas, undifferentiated adenocarcinomas, and clear cell carcinomas demonstrated intense staining of ras p21. The frequency and intensity of ras p21 staining were observed to increase with the degree of malignancy. There was no significant difference in ras p21 expression between early and late stages in ovarian tumors arising from the coelomic epithelium. With respect to prognosis, no differences between the ras p21-positive and -negative cases in ovarian tumors arising from the coelomic epithelium were observed. It is, therefore, possible to say that ras p21 expression was not related to clinical staging and prognosis. Expression of ras p21 in malignant lesions was higher than that in benign lesions of the ovary, and the expression is associated with the degree of malignancy in some types of ovarian tumors. Overexpression of ras p21 was observed in epithelial tumors; however, increased expression was not observed in germ cell and sex-cord stromal tumors. This differential expression of ras p21 is due to the different histogenesis of ovarian tumors. This fact may reflect a different carcinogenic mechanism for different types of malignancy. PMID- 1634141 TI - Papillary serous adenocarcinoma of the endometrium: a clinicopathologic study of 19 cases. AB - Survival in 19 patients with papillary serous adenocarcinoma of the endometrium treated at the University of Vermont during the period 1960-1987 was significantly worse than that for 360 patients with other types of endometrial cancer. Deaths were associated with extrauterine spread and deep myometrial invasion detected at the time of surgery. Two patients without myometrial invasion and with extrauterine spread who also died may have developed synchronous peritoneal serous carcinoma. PMID- 1634142 TI - Inexpensive population screening for abnormal cells from the uterine cervix and valid results using the vaginal cytopipette. AB - Women who have not accepted an invitation by their own general practitioner to have a smear test, or for whom voluntary population screening projects are unavailable because of lack of public funds, may be at increased risk of malignant cervical changes. Such women may be offered self-testing by a cytopipette on the basis of the present analysis of abnormal cell counts and cell density on the cytological slides. As one link in a prophylactic study using the cytopipette, 107 women with abnormal cell findings were reinvited for simultaneous sampling by irrigation smear and by ordinary technique. The cytological findings indicate that the two methods are equal in recovery of abnormal epithelium, provided that the scanned quantity of cells is increased fourfold in the irrigation smear method, this quantity being distributed over two specimens each with double cell density and giving at least 1800 squamous epithelial cells per visual field (125:1) or a total of approximately 10(6) epithelial cells in each cytological specimen. Under these conditions the two sampling methods have the same predictive value. PMID- 1634143 TI - Serum erythropoietin levels in gynecologic cancer patients during cisplatin combination chemotherapy. AB - To investigate the participation of erythropoietin (Epo) in anemias induced by cisplatin combined chemotherapy, serum Epo levels were measured by radioimmunoassay on a serial basis in eight patients with gynecologic cancer undergoing this chemotherapy. The data demonstrated that serum Epo levels, the mean level before chemotherapy being 20.1 +/- 6.6 mU/ml, were significantly elevated after the first course of the chemotherapy (52.1 +/- 32.2 mU/ml; P less than 0.05) when anemia was not evident. The serum Epo level continued to increase as the course of chemotherapy advanced, and furthermore, patients with normocytic anemia after a multiple course of this chemotherapy still showed high Epo levels (115.2 +/- 53.5 mU/ml) that were appropriate for given degrees of anemia. It is suggested that cisplatin combined chemotherapy caused the elevated serum Epo levels through an unknown mechanism other than anemia, and that in anemias induced by cisplatin, Epo deficiency is not evident. PMID- 1634144 TI - Potentiation of cisplatin cytotoxicity in human ovarian carcinoma cell lines by trifluoperazine, a calmodulin inhibitor. AB - Chemotherapy for ovarian cancer is frequently limited by cisplatin (CDDP) resistance. Enhanced DNA repair is one of several mechanisms which may cooperate to produce resistance in human ovarian carcinoma cell lines. Published reports suggest that calmodulin inhibitors, such as trifluoperazine (TFP), may inhibit one or more steps in DNA repair. The effects of TFP alone or in combination with CDDP were determined by clonogenic assay of six human ovarian carcinoma cell lines, derived from untreated patients (some of which were selected for cisplatin resistance in vitro) and from patients clinically refractory to cisplatin-based chemotherapy. TFP produced dose-dependent cytotoxicity in all cell lines. In addition, TFP (10 microM) produced approximately two-fold enhancement of CDDP cytotoxicity in three of the six cell lines (A2780, 2780-CP8, and 2780-C30). TFP and CDDP had additive or synergistic cytotoxicity in four of the six cell lines by median effects analysis, while clear antagonism was apparent in the remaining cell lines. These results suggest that TFP may enhance CDDP cytotoxicity in some, but not all, human ovarian carcinoma cell lines. The potential utility of trifluoperazine in ovarian cancer, either alone or in combination with cisplatin, remains to be defined in xenograft models and in clinical trials. PMID- 1634145 TI - The use of ATP bioluminescence assay and flow cytometry in predicting radiosensitivity of uterine cancer cell lines: correlation of radiotoxicity and cell cycle kinetics. AB - Radiotherapy remains an important part of uterine cancer treatment. This study was designed to evaluate the potential of the ATP bioluminescence assay and flow cytometry for predicting radiosensitivity. Correlation of these two modalities revealed important insights into the relationship of radiotoxicity and cell kinetic effects. Six human uterine cancer cell lines were used: AE7, ECC1, HEC1A, HEC1B, AN3, and SKUT1B. Doses of cobalt 60 were 0, 1, 2, 5, 8, and 10 Gy. The ATP bioluminescence assays were performed on Day 7. Cell samples were taken at 0, 24, 48, 72, 96, and 168 hr for flow cytometry. The linear-quadratic model was used to fit survival data and mean inactivation dose D was calculated. Among parameters such as D, alpha and beta coefficients, and surviving fraction at 2 Gy (SF2), both D and SF2 correlated best with survival data. Radiation effects on the cell cycle did not correlate with D and revealed two distinct patterns: either a G1 accumulation with mild G2 block or a G1 depletion and severe G2 block. The S cells consistently demonstrated a biphasic pattern with an initial reduction followed by an accumulation. In summary, the ATP assay was shown to have potential in the study of radiosensitivity. Radiation-induced cell kinetics appeared to vary with intrinsic cellular differences and, thus, could not be used to predict radiosensitivity. PMID- 1634146 TI - DNA content in juvenile granulosa cell tumors of the ovary: a study of early- and advanced-stage disease. AB - Paraffin-embedded tissue from 38 patients with early- and advanced-stage juvenile granulosa cell tumor (JGCT) of the ovary was analyzed by flow cytometry to investigate whether the DNA content is related to the histologic features, stage, or clinical outcome. Thirty-three cases were suitable for analysis: twenty-seven Stage Ia, two Stage Ic, and four Stage III. Eighteen (55%) tumors were DNA diploid and fifteen (45%) tumors were DNA aneuploid with a mean S-phase fraction (SPF) of 13.6% and a range of DNA indices from 1.0 to 2.2. Neither the DNA ploidy nor the SPF was associated with the stage of the disease. An analysis of the relation between DNA content and histopathologic features revealed that aneuploidy was associated with high mitotic rates and to a lesser extent with high-grade nuclear atypia. DNA aneuploidy was not associated with aggressive behavior of Stage Ia JGCTs. However, among the four patients with Stage III tumors, the two with diploid, low-SPF tumors were alive and well, whereas the two with aneuploid, high-SPF tumors developed recurrences or died. These data suggest that further studies on the prognostic significance of flow cytometric analysis of DNA content in advanced-stage JGCTs are warranted. PMID- 1634147 TI - Marginal fractures of the lateral malleolus in association with other fractures in the ankle region. AB - Eight cases of avulsion-type fracture of the distal fibula associated with fracture of the calcaneus, talus, or ankle region were identified. This avulsion fracture can be identified on routine radiographs as well as on CT scans of the ankle and is pathognomonic of rupture of the superior peroneal retinaculum with or without peroneal tendon displacement. Recognition of this avulsion fracture, with subsequent proper management of the underlying peroneal tendon pathology by immobilization or surgery, may prevent future tendon dysfunction. It may also alter the treatment of other associated injuries. PMID- 1634148 TI - Treatment of extensive aseptic defects in old Achilles tendon ruptures: methods and case reports. AB - Defect bridging is still problematic in the secondary treatment of Achilles tendon ruptures. Smaller defects can be treated without problems by the well known standardized methods, whereas other methods have to be applied for treating larger defects. Free transplants with autogenous or exogenous material should be mentioned in this context. Complications are more likely to occur with exogenous material, free transplants from the fascia lata require an additional intervention to remove the transplant from another localization. These methods cannot be applied to achieve reliable restoration of continuity for defects with a length of 10 cm. Therefore, in these special cases, we carry out the tendon transplantation with a free tendon-muscle graft from the triceps surae muscle. We achieved reliable restoration of continuity with complication-free healing of the free transplant in, up to now, three cases, in association with the formation of a strong, functionally high grade scar plate in the area of the tendon. PMID- 1634149 TI - Stabilization of the interphalangeal joint of the big toe: comparison of three methods. AB - Three methods of stabilizing the IP of the big toe were compared. In group A, 10 patients underwent tenodesis of the extensor hallucis longus to the extensor digitorum brevis tendon. All of them developed a toe-drop; two patients had significant symptoms that required IP fusion. In group B, 19 patients underwent IP fusion using smooth or threaded intramedullary Kirschner wire fixation. There were nine nonunions, three requiring refusion. In group C, 32 patients underwent IP fusion using intramedullary screw fixation. There was one nonunion with screw failure that required revision. Although none of our patients considered the toe drop after extensor hallucis longus tenodesis cosmetically unacceptable, this may not be so in other cultures. All complications following IP fusion with screw fixation were technical and are avoidable. When stabilization of IP is required, we recommend fusion of IP with screw fixation. PMID- 1634150 TI - Plantar fasciotomy for intractable plantar fasciitis: clinical results and biomechanical evaluation. AB - Thirteen consecutive patients underwent plantar fasciotomy in 16 feet for intractable plantar fasciitis and had follow-up from 4.5 to 15 years. Plantar fasciotomy was successful (good or excellent results) for 71% of the 14 feet operated on and for which follow-up data were available. However, time to full recovery was prolonged, additional treatment was frequently required, and abnormalities of foot function persisted. Flattening of the longitudinal arch occurred. Dynamic force-plate studies showed differences in peak vertical, fore aft, and lateral-medial forces between patients and matched controls. More rapid progression of weightbearing along the longitudinal axis of the foot during stance phase in patients indicated avoidance of heel loading. PMID- 1634151 TI - Tibial sesamoid shaving for treatment of intractable plantar keratosis. PMID- 1634152 TI - The distal course of the sural nerve and its significance for incisions around the lateral hindfoot. AB - Twenty preserved cadaver limbs were dissected to show the distal course of the sural nerve and the number and site of origin of its branches. The mean position of the main nerve trunk was calculated at various points related to bony landmarks of the fibula and the fifth metatarsal base. Ninety-five percent confidence limits for the course of the main nerve trunk could be described. A fibula incision may damage the nerve if it extends more than 7 mm inferior to the lateral malleolar tip with the foot in equinus. Dorsolateral foot incisions may damage both the main trunk and the major anterior branch. PMID- 1634153 TI - The retrocalcaneal bursa: anatomy and bursography. AB - The retrocalcaneal bursae, located between the posterior angle of the os calcis and the Achilles tendon, may become inflamed and hypertrophied. There are few objective tests available for the diagnosis of pain syndromes involving the hindfoot and it is often difficult to differentiate Achilles tendinitis and retrocalcaneal bursitis. Retrocalcaneal bursograms can provide further insight into chronic changes in the bursae associated with traumatic and inflammatory conditions. This report describes the anatomy of the retrocalcaneal bursa, the technique of its opacification, and the application of this technique to the diagnosis and treatment of painful hindfoot syndromes. In addition, the anatomy of the retrocalcaneal bursa was investigated further using latex casting techniques. Twelve cadaver limbs were injected with radiopaque latex casting material or renografin into the retrocalcaneal bursae. AP, lateral, and oblique radiographs were then obtained on the specimens. The size, capacity, and configuration of the postmortem bursae were measured and recorded. Subsequently, the cadaver limbs injected with the latex material were cooled and dissection was made of the retrocalcaneal bursae. The latex bursal molds were measured, graphically recorded, and photographed. Fifteen patients with signs and symptoms of retrocalcaneal bursitis and eight asymptomatic patients were selected for this study and injected with radiopaque material into the bursae. Anteroposterior, lateral, and oblique radiographs were then obtained. The size, capacity, and configuration of the retrocalcaneal bursae were measured and recorded. The anatomic characteristics noted from the latex bursal molds correlated well with the findings on bursography. Bursographic findings in patients with retrocalcaneal bursitis can provide insight into the diagnosis and clinical management of this disorder. PMID- 1634154 TI - Clinical significance of magnetic resonance imaging in preoperative planning for reconstruction of posterior tibial tendon ruptures. AB - A retrospective study of attenuated/ruptured posterior tibial tendons was conducted of all patients who underwent tendon reconstruction over a 4-year period. The study comprised 20 feet in 19 patients having an average age of 53.3 years, with an average follow-up of 2 years. Preoperative magnetic resonance images were taken and graded for assignment to one of three magnetic resonance imaging (MRI)-based groups. The surgical grade was determined intraoperatively based on a previously described classification scheme. No medical or rheumatologic conditions predisposing to failure could be identified. Failure was defined as postoperative progression of pain and deformity which required subsequent triple arthrodesis. There were six failures at an average of 14.7 months. Surgical evaluation was not correlated to outcome following reconstruction. MRI grading, however, was predictive of outcome. The superior sensitivity of MRI for detecting intramural degeneration in the posterior tibial tendon that was not obvious at surgery may explain why MRI is better than intraoperative tendon inspection for predicting the outcome of reconstructive surgery. Therefore, it may be helpful to obtain preoperative MRI when this particular reconstruction of the posterior tibial tendon is contemplated, since this provides the best measure of tendon integrity and appears to be the best predictor of clinical success after such surgery. PMID- 1634155 TI - Dislocation of the posterior tibial tendon. AB - We have treated seven patients with dislocation or recurrent subluxation of the posterior tibial tendon. The diagnosis of dislocation was made based on the patient's symptoms, physical examination, and magnetic resonance scanning. All patients were treated with surgical repair, which was modified according to the operative findings. The operative findings included tenosynovitis, a shallow or incompetent flexor groove, and tearing or absence of the flexor retinaculum. At an average of 28 months following surgery, all patients were markedly improved and six returned to their preinjury level of activity. PMID- 1634156 TI - A technique for measuring absolute toe pressures: evaluation of pressure sensitive film techniques. AB - Although a number of pathologies of the forefoot in ballet dancers on pointe have been described, pressures and deforming forces have not been adequately measured. To evaluate the possible use of pressure-sensitive film (PSF) in measuring the pressures on the external soft tissues in such a confined space as the dancer's toe shoe, it was tested and calibrated with 20 cadaver toes. Each cadaver toe was internally stabilized and loaded longitudinally against PSF on a flat surface. The resultant films were analyzed with a video imaging system and the pressures and total forces were determined. Results showed that the linearity of the PSF to pressure had a regression value of 0.98. By using two sensitivity ranges of films, the total force measured by the PSF was found to be within 10% of the known applied force on each toe. The PSF, therefore, may very well be a useful and accurate method of measuring external soft tissue pressures on the forefoot. PMID- 1634157 TI - Repair of concomitant lateral ankle ligament instability and peroneus brevis splits through a posteriorly modified Brostrom Gould. PMID- 1634158 TI - [Increasing the adhesion of glass ionomer cements in bracket bonding]. AB - For attaching orthodontic brackets glass ionomer cements are being discussed as an alternative material to synthetic glues since they are less aggressive toward the tooth enamel. A serious disadvantage consists in a lower degree of adhesion to enamel. The adhesion can, however, be increased to some extent by enamel preparation. In order to investigate further improvement in this area, 250 freshly extracted bovine teeth were treated with 22 chemicals and their enamel conditioning properties were tested. For the attachment of the brackets the glass ionomer cements AqaCem and Ketac-cem are used. Tensile shear tests were carried out with a Wolpert universal testing machine. Best results were obtained with the aromatic carbonacids benzoic acid and salicylic acid in acetonic solution. The mean adhesive power was 9.8 MPa. This means an increase of 38% as compared to other pre-conditioning materials such as polyacrylic acid. It can be assumed, that aromatic carbonacids as small, very reactive molecules can establish a closer contact to the phosphate groups of enamel than can the macromolecular polyacrylic acid. Thus, a further step on the way to using glass ionomer cements as a bracket bonding material seems to have been taken. PMID- 1634159 TI - [The importance of the center of resistance for the biology of tooth movement]. AB - The tooth movement of loaded premolars was investigated in four two-years-old beagle dogs under general anesthesia. Two supragingival registrations were performed to calculate the center of rotation in order to estimate the amount of tipping. Loads of 5 to 20 N were applied for two to four seconds. The amount of tipping was found to be load- and time-dependent. The discrepancy between these findings and the models of analytical mechanics were explained by bone bending in our experiments. Biology and localization of periodontal remodelling is supposed to be dependent on load magnitude, load duration and physical properties of all periodontal tissues including bone. PMID- 1634160 TI - [The tensile bonding strength of metal plasma-coated bracket bases]. AB - The tensile bond strength of bracket bases coated with metal plasma were examined. The aim was to investigate, whether the conditioning of bracket bases by metal plasma is a possible means to increase the tensile bond strength. Two typical orthodontic adhesives were used. Three test groups were differentiated: 1. Metal mesh bracket bases (coated and uncoated with metal plasma), 2. metal bracket bases without mesh (coated with metal plasma), 3. ceramic bracket bases coated with metal plasma. Metal bracket bases with mesh, coated with metal plasma showed superior bond strength in comparison to usual uncoated mesh bracket bases. The former were nearly four times stronger than the uncoated bases with reference to the first adhesive and two times stronger referring to the second adhesive. The primary source of the enhancement of adhesion is due to the enormous increase of the retentive active surface created by the metal plasma. This structure guarantees an excellent micromechanical interlocking for the adhesive. The mean tensile bond strength of titanium coated mesh bases was 20.03 N/mm2 (= 286 N/bracket). Plasma coated bases without mesh reached average interlocking forces comparable to conventional uncoated mesh bases. Ceramic bracket bases were found not to be suitable for plasma coating. As a result of these experimental findings metal plasma coating of metal bracket bases can be regarded as an excellent means to increase the tensile bond strength. PMID- 1634161 TI - [The orthodontic treatment of deep bite in adults--a comparison of the straight wire appliance and the segmented arch technic]. AB - The purpose of the study was to analyse and compare deep overbite correction in adult patients carried out by a straight wire appliance and the segmented arch technique as recommended by Burstone. The sample comprised 50 adult, deep bite patients, 25 each treated with straight wire appliance and segmented arch technique. Plaster casts and lateral cephalograms made before and immediately after finishing treatment were analysed. Both techniques were successful in overbite correction; overbite reduction amounted to 3 to 3.5 mm. The straight wire appliance group demonstrated predominantly molar extrusion and as a result posterior mandibular rotation. A slight intrusion of 1 mm was seen in the lower incisor area. The segmented arch technique resulted in an incisor intrusion of 1.5 mm in the upper and 1.7 mm in the lower jaw. No substantiate extrusion in the molar area was found. The advantages of this technique are discussed. PMID- 1634162 TI - [The subjective and objective assessment of the long-term follow-up findings an average of 17 years after the conclusion of therapy]. AB - Posttreatment and seven to 28-year postretention records and actual questionnaires of 240 orthodontically treated patients were assessed to evaluate dental awareness and the patients evaluation of posttreatment changes. 80% have regular dental visits and 44% of them have periodontal disease whereas 60% of those who responded having irregularly or no dental controls. 38% were aware of posttreatment changes, only increased and decreased overjet showed a significance in patients evaluation and objective situation. PMID- 1634163 TI - [The periodontal changes following orthodontic tooth movement--a retrospective histological study in humans. 1]. AB - The maxilla of a deceased (19 years, female) who was treated with a straight-wire appliance could be taken in autopsy. The specimen was prepared histologically in the horizontal plane. The type of tooth movement was reconstructed by comparing the treatment documents of the beginning (photo of the cast model, radiograph) with the photo and radiographs of the specimen. In that manner the histological findings could be correlated with the type of tooth movement. RESULTS: Localisation and amount of tissue changes at the roots depend on the type of tooth movement and the morphology of bone. The histological findings are more pronounced than the radiographs show. Histologically verified bony dehiscences in the facial or oral cortical plate are not to be diagnosed by macroscopic inspection of the specimen. PMID- 1634164 TI - [The treatment of open bite using magnets]. AB - Until recently, surgical correction of the jaws has been widely regarded as the most effective treatment of open bites in the permanent dentition. In the following case report an open bite was treated non-surgical by intrusion of the molars with a magnet appliance. The forces of repelling magnets, fixed opposite in the upper and lower jaw were used to intrude the first and second molars. This intrusion allowed an autorotation of the mandible upward and forward to close the open bite. By reduction of the open bite of about 3 mm a surgical intervention could be avoided. PMID- 1634165 TI - [Additional therapeutic approaches after coronary thrombolysis]. PMID- 1634166 TI - [Proctalgia fugax. Differential diagnosis and therapy of fleeting anal cramp]. AB - Proctalgia fugax--short-lived anal spasm--is a common, extremely unpleasant, painful condition that occurs completely unexpectedly, often waking the victim at night. Scientific assessment is difficult on account of the functional nature of the condition and its multifactorial genesis. Before the patient is labeled "anal neurotic", however, he/she should be investigated by a specialist. The results of treating the rarely absent pathological organic findings give rise to optimism. PMID- 1634167 TI - [Resuscitation in cardiovascular arrest. Part 1: Basic measures, ventilation and heart massage]. PMID- 1634168 TI - [Erythema infectiosum infection can cause intrauterine fetal death. Possibilities of diagnosis and treatment]. PMID- 1634169 TI - [Crataegus in cardiology]. AB - The fact that the effectiveness of numerous phyto-preparations, so-called, has been demonstrated to the satisfaction of traditional medicine has led to increasing interest in phytotherapy. This also applies to Crataegus (whitethorn), the effects of which have been demonstrated in numerous pharmacological studies. These effects, produced mainly by the flavonoids, indicate a simultaneous cardiotropic and vasodilatory action, as confirmed clinically in controlled double-blind studies. This means that Crataegus can be employed for cardiological indications for which digitalis is not (yet) indicated. Prior to use, however, a Crataegus preparation must meet certain preconditions with respect to dosage, pharmaceutical quality of the preparation, and an accurate definition of the later. PMID- 1634170 TI - [Andrologic expert assessment. Experiences and results of 40 years]. AB - On the basis of 300 andrological expertises made over the last 40 years to answer the question as to procreative capacity and other andrological problems, a position is taken up towards the expertise in general and to a number of characteristic data. In more than 95 percent of the cases, there was agreement between the conclusions of the expert and the subsequent decision taken by the client. It is emphasized that, within the period considered, there has been a general decrease in requests for expert opinions on procreative capacity in paternity suits, which is traced back to the increasing accuracy of the methods of blood group serology. In contrast, expertises in the case of occupational accidents, criminal offences and errors in medical treatment are on the increase. PMID- 1634171 TI - [Photodynamic laser therapy with antibody-bound dyes. A new procedure in therapy of gynecologic malignancies]. AB - In the present paper, a new therapeutic concept of photodynamic laser therapy using antibody-linked dyes for the treatment of gynecological malignancies is described. So far, HPD (hematoporphyrin derivative) has been employed in this area, but is associated with toxic systemic reactions. We see a solution to this problem in the linking of a systemically non-toxic dye--known to induce photodynamic reactions while not itself being selectively accumulated within tumor cells--to an antibody directed against a selective tumor-associated antigen. The results of our study demonstrate the efficacy of this therapeutic concept as exemplified by the selective destruction of dye-labeled ovarian carcinoma cells by laser light of a defined wavelength (675 nm). The potential of this form of photodynamic therapy extends far beyond its use in ovarian carcinoma. PMID- 1634172 TI - [Resuscitation in cardiovascular arrest. Part 2: Expanded resuscitation measures]. PMID- 1634173 TI - [Local therapy of grade 1 and 2 hemorrhoids. Effectiveness of a combination preparation with standardized blood leech extract]. AB - AIMS: Testing the effectiveness of a topical combination preparation containing standardized leech extract, polidocanol and allantoin. STUDY DESIGN: Placebo controlled, double-blind study in 80 patients with first and second degree hemorrhoids; duration of treatment one week; examinations performed on admission and on days 3, 4, 5 and 8. RESULTS: Both the subjective and objective symptoms and signs improved during the one week of treatment statistically significantly more rapidly under the test preparation as compared with placebo. Histologically demonstrable signs of inflammation were more clearly improved in the preparation group than in the placebo group. No side effects were observed. CONCLUSIONS: The good efficacy and tolerability of a topical therapeutic preparation in first and second degree hemorrhoids have been convincingly demonstrated. PMID- 1634174 TI - [Anorexia nervosa and bulimia. New research results--success with behavior therapy]. PMID- 1634175 TI - Zenker's diverticulum and reflux. AB - The interrelationship between gastroesophageal reflux and Zenker's diverticulum remains unclear. The view that cervical diverticula are induced by gastroesophageal reflux disease (GER) is apparently supported by epidemiologic observations indicating that they occur only in populations with a high incidence of GER. However, it is difficult to prove causality on the basis of currently available physiological and pathophysiological investigations. The few data published to date now end to support a cryptogenic change in upper esophageal sphincter (UES) muscle motility characteristics instead of a reflux induced lesion to the UES. Clinical experience also shows that GER does not play a major role in individual cases of Zenker's diverticula, nor do many surgeons consider it a risk following cervical myotomy. This is confirmed by a very low complication rate even in large series of patients in whom no attempt was made preoperatively to rule out concomitant reflux disease. In conclusion, some facts suggest that reflux disease may be a cause of the development of Zenker's diverticulum. In the majority of cases, however, autochtonic structural lesions to the UES muscle fibers or other, as yet unknown, reasons are more probable. PMID- 1634176 TI - Endoscopic treatment of the hypopharyngeal (Zenker's) diverticulum. AB - Over the years the techniques for endoscopic treatment of Zenker's diverticulum have been improved. Initially, in 1964, we used the electrocoagulation technique as described by Dohlman, but currently we prefer to sever the tissue bridge between the diverticulum and esophagus with the CO2 laser under microscopic control. The results of endoscopic treatment in 507 patients with a diverticulum are discussed. It is concluded that endoscopic treatment can readily be performed with good results, especially in the case of elderly patients in a poor general condition. PMID- 1634177 TI - The treatment of pharyngoesophageal diverticulum: the simple and complex. AB - Over 900 patients have been treated at the Mayo Clinic for Zenker's diverticulum since 1944 using a one-stage transcervical diverticulectomy under general anesthesia. Overall results have been very good, but not entirely free of morbidity or mortality. An attempt is made to define those circumstances in which the procedures used have either been judgmentally or technically difficult or in which morbidity or mortality has occurred. These include patients with concomitant medical or surgical problems, or complexity related to the diverticulum itself. Among the latter are huge or giant sacs, patients with severe nutritional and respiratory symptoms related to aspiration, the perforated diverticulum, reoperation for recurrent diverticulum and cancer in a diverticulum. PMID- 1634178 TI - Manometric aspects of Zenker's diverticulum. AB - Zenker's diverticulum is thought to result from disordered coordination between the pharynx and upper esophageal sphincter. Manometric studies of the upper esophagus have been helpful in testing the hypothesis of dysmotility in the formation and growth of a Zenker's diverticulum; however, the data have provided conflicting evidence. Manometric studies show that resting upper esophageal sphincter pressure is normal in some patients with Zenker's diverticulum and decreased in others. Abnormal premature relaxation and contraction of the upper esophageal sphincter seen in some patients with Zenker's diverticulum may be accompanied by pharnygeal contractions against a closed sphincter. This abnormality is thought by some investigators to be the cause of Zenker's diverticulum, but not by others who have found normal upper sphincter relaxation. Future manometric studies will very likely elucidate the pathogenesis of Zenker's diverticulum. PMID- 1634179 TI - Zenker's diverticulum: is a myotomy of the cricopharyngeus useful? How long should it be? AB - In a series of 100 consecutive patients surgically treated for Zenker's diverticulum (ZD) biopsy specimens were taken at the level of the cricopharyngeal muscle in 62 patients and also at the level of the striated muscle wall of the cervical esophagus in 10 patients. Contractility, pathological enzymo- and immunohistochemical characteristics were studied in comparison with a group of 15 controls. Obvious pathological findings were noted in 95% of the ZD specimens as compared with the control specimens. These pathological changes, although somewhat less pronounced, were also documented in the biopsy specimens taken at the level of the striated cervical muscle wall. The findings were judged important enough to justify a long extramucosal myotomy of the cricopharyngeal muscle and cervical esophagus as an essential step in the treatment of ZD. The treatment of choice in this series was a diverticulopexy and a four to five centimeter long extramucosal myotomy, starting from the cricopharyngeal muscle and extending downwards into the striated muscle wall of the cervical esophagus. Excellent or very good results were obtained in 96% of the patients with respect to diverticulum-related symptoms. PMID- 1634180 TI - Surgical management of Zenker's diverticulum. PMID- 1634181 TI - The natural history of duodenal ulcer disease. AB - With a view to describing the natural history of duodenal ulcer, currently linked with powerful and widely used drugs, we retrospectively reviewed all patients followed-up at our unit between 1978 and 1989. All DU subjects with at least 5 years of clinical-endoscopic follow-up were admitted to the study. Concomitant gastric ulcer, previous gastrointestinal surgery and treatment other than with H2 blockers (where necessary) were considered exclusion criteria. Forty-four patients (35 males, 9 females, mean age 44.5) proved eligible for this study. At monthly intervals in the patients' history of ulcer disease (starting from a baseline month 0 when ulcer symptoms first appeared), we compared all cases in which the duration of disease coincided, i.e. for each month of the clinical course of the ulcer there was a certain number of patients at the same point in time; patients' histories coincided variously over a period ranging from 0 to 15 years. We considered endoscopically-diagnosed relapses (both symptomatic and asymptomatic) and hemorrhages as marker events for the activity of DU disease. A year-by-year duodenal ulcer activity rate was obtained for both treated and untreated subjects, as follows: No. of events/mean No. of patients followed-up per month x 100. Fisher's exact test and multivariate analysis (stepwise logistic regression) were used to investigate risk factors of poor outcome. We found that the years between the 1st and 5th and between the 10th and 15th from the onset of duodenal ulcer disease had higher peaks of activity, mostly in untreated subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634182 TI - Hemosuccus pancreaticus from a pseudoaneurysm of the hepatic artery proper in a patient with a pancreatic pseudocyst. AB - Pseudoaneurysms of the visceral arteries due to pancreatitis, with subsequent rupture and hemorrhage into the pancreatic duct are unusual. To date, three cases of pseudoaneurysm of the hepatic artery with hemosuccus pancreaticus have been reported in the literature. We describe a case of a pseudoaneurysm of the hepatic artery proper, which ruptured into a pancreatic pseudocyst communicating with the pancreatic duct, and which was the cause of upper gastrointestinal bleeding. This case was successfully managed by resection of both the pseudoaneurysm and the pancreatic pseudocyst. PMID- 1634183 TI - Therapeutic embolization of post-cholecystectomy hepatic artery aneurysm. AB - A "sandwich" technique employing steel coils and gelfoam embolization was applied in two cases of hepatic artery aneurysms. Immediate cessation of the bleeding was evident clinically and the post-embolization angiogram showed occlusion of the vascular lesion. Cholecystectomy is one of the most common abdominal operations and it is generally well tolerated, particularly in young and middle-aged patients. Morbidity rates of 5% to 32% and mortality rates of 0.4% to 2.5% have been reported, depending on such factors as age, underlying illness, etc. (1-4). The most frequent complications of cholecystectomy are wound infection, abscess, ductal injury or ligation, and bleeding. This paper describes two cases of hepatic pseudoaneurysm following iatrogenic damage during cholecystectomy which was treated with transarterial embolization. PMID- 1634184 TI - Serum bile acids and the bile acid tolerance test under oral contraception. AB - Oral contraceptives (OC) have lithogenic properties as shown by a rise in biliary cholesterol secretion and cholesterol saturation index. Since we noted not only a rise in saturation index, but also a reduction in chenodeoxycholate (CDC) pool size and an increase in cholate (C) pool size during oral contraception (30 micrograms ethinylestradiol + 150 micrograms desogestrel), we investigated the endogenous bile acid tolerance test as a potential predictor of this effect on bile acid pool sizes using a cholecystokinin infusion of 55 min duration (1.2 U.kg-1.hr-1) as stimulus of the enterohepatic bile acid circulation in 12 healthy females before and during oral contraception for 3-5 months. Serum C and CDC conjugates were measured at 5-10 min intervals over a period of 150 min and analysed by two specific RIA's. Although no significant correlations between the serum CDC and C measurements and CDC and C pool sizes were found, a significant reduction of nearly 40% for both serum peak levels and the integrated area under the serum curve of CDC conjugates during oral contraception, but not of C conjugates was found. The reduction in serum levels of CDC conjugates during OC using the present model is best explained by both a reduction in CDC pool size and more efficient hepatic uptake of CDC conjugates (consisting of considerably more taurine conjugates during OC use), as well as by an intestinal effect on bile acid absorption under OC. PMID- 1634185 TI - Clinical relevance of anorectal function investigations. AB - Anorectal function tests are often performed in patients with anorectal disorders. The test results have shown considerable overlap between normal controls and patients. Therefore, purely clinical indications for the individual anorectal function tests are few, and the strength of these tests lies in their combination. When the patient is not eligible for surgery or biofeedback, there is no indication for these tests. PMID- 1634186 TI - Pressure and X-ray recording of reflux into the thoracic stomach. AB - Anastomotic leakage, pulmonary aspiration and reflux-esophagitis might be induced or aggravated by the increased duodenogastric reflux observed in the thoracic stomach. In this study, the effect of respiration on the reflux-promoting pressure gradient in the intrathoracally located stomach was assessed. In nine patients pressure recording was done in the duodenum and the abdominal and thoracic part of the stomach. Intrapleural pressure was determined by recording mouth pressure during inspiratory occlusion. In addition, the course of injected contrast was examined fluoroscopically. The mean end-expiratory pressure gradient in the thoracic part of the stomach was 0.8 cm H2O, increasing up to 6.0 cm H2O and 21.3 cm H2O during normal and forced inspiration, respectively. Fluoroscopic examination showed reflux of contrast that coincided with the downward movement of the diaphragm. From this study, we conclude that reflux into the thoracic stomach is promoted by intraluminal pressure fluctuations induced by voluntary breathing. Performing a pyloroplasty or -myotomy after intrathoracic esophagogastrostomy destroys the integrity of the pyloric sphincter as a barrier to reflux, thus promoting duodenogastric reflux. PMID- 1634187 TI - Esophageal diverticula. PMID- 1634188 TI - Surgical management of esophageal thoracic diverticula. AB - Between 1969 and 1989, thirty-three patients were admitted for the treatment of a mid- or lower thoracic diverticulum and were investigated. Their mean age was 63 years. The predominant symptoms were dysphagia and regurgitations of, on average, 5.8 years' duration. Three patients had associated carcinoma and were excluded from the study. Three patients with mild complaints were managed medically and 27 surgically. Surgical treatment included, prior to 1979, simple diverticulectomy in 10 patients since 1970 diverticulectomy and myotomy through a right thoracic approach in one patient diverticulectomy, esophageal myotomy and fundoplication through a left thoracic approach in 10 patients and simple abdominal esophageal myotomy with fundoplication in 4 patients. In 2 patients, an esophagobronchial fistula was successfully treated. There were 3 postoperative deaths (2 suture line leakages and one massive aspiration pneumonia). Two patients had persistent dysphagia: one was reoperated on for a subsequent abdominal esophageal myotomy and the other one for severe reflux esophagitis following esophageal dilatations. Four patients had reflux esophagitis and two were reoperated on for a total duodenal diversion. The importance of the long esophageal myotomy extended on to the cardia through a left thoracotomy, and of a good antireflux procedure after the myotomy, in the treatment of thoracic esophageal diverticula is emphasized. PMID- 1634189 TI - Effects of alloxan-induced diabetes on hemorheology in rabbits. AB - Plasma viscosity (PV), apparent whole blood viscosity (WBV), relative blood viscosity (RV) and erythrocyte deformability (filterability) (EDF) were determined in 13 New Zealand White (NZW) rabbits with alloxan induced-diabetes (AID) and 8 normal NZW rabbits, matched for age, sex and weight. AID rabbits were divided into two groups depending on the duration of hyperglycemia (long-term, greater than 6.0 months (n = 7), and short-term, less than or equal to 3.0 months of hyperglycemia, n = 6). Comparing long-term AID rabbits to normal animals, we found significant increases in WBV (P less than 0.001, 0.005 for high and low rates of shear, respectively), and a marked reduction in EDF (P less than 0.001). There was no significant difference in PV between long-term AID and normal rabbits. Conversely, PV was significantly increased in rabbits with short-term diabetes (P less than 0.01) while there was a concurrent significant increase in WBV measured at high and low rates of shear (P less than 0.001, 0.001, respectively). No difference was detected in EDF between normal and short-term AID rabbits. Furthermore, in long-term AID rabbits there was a strongly positive correlation between RV and reduced erythrocyte deformability (r = 0.94, P = 0.006) while WBV strongly correlated with PV (r = 0.92, P = 0.004) in the short term AID subgroup. We conclude from these data: (1) elevated blood viscosity in long term AID rabbits is associated with reduced erythrocyte filterability; and (2) elevated WBV in short-term AID rabbits is associated with increased PV. PMID- 1634190 TI - Increased ketogenesis related to insulin deficiency in isolated hepatocytes from NIDDM model rats. AB - To investigate the hepatic ketone body metabolism in NIDDM, we studied the ketone body production rates in hepatocytes from newly developed non-obese NIDDM model rats. NIDDM model rats were prepared by intraperitoneal injection of streptozotocin at 2 or 5 days of age (STZ2, STZ5 respectively). After 10-15 weeks, ketone body production rates in hepatocytes isolated from these rats were compared with those from control rats as well as ketotic rats made by intravenous injection of streptozotocin into adult rats. Basal ketone body production rates from 0.3 mM [U-14C] palmitate in hepatocytes from control, STZ 2, STZ 5 and ketotic rats were 11.7 +/- 0.98, 14.9 +/- 0.72, 16.0 +/- 0.45, 22.8 +/- 2.32 nmole.palmitate/mg.prot/hr, respectively. These rates were stimulated by 1 microgram/ml of glucagon in control, STZ 2 and STZ 5 rats (14.1 +/- 0.99, 18.6 +/ 1.36, 18.7 +/- 0.69 nmole.palmitate/mg.prot/hr, respectively), but not in ketotic rats (22.8 +/- 2.07 nmole.palmitate/mg.prot/hr). The similar effects were observed by 1 microgram/ml of epinephrine. The basal ketone body production rates were negatively correlated to both hepatic glycogen contents and plasma IRI levels. Considering these parameters together, the extent of metabolic derangement in STZ 2 and STZ 5 rats was between that in control and ketotic rats. These results indicate that the derangements of hepatic ketone body production are related to the severity of insulin deficiency and suggest that the enhanced hepatic ketogenesis contributes in part to the elevated plasma ketone body levels in non-obese NIDDM. PMID- 1634191 TI - Effects of dopamine on the release of thyrotropin-releasing hormone from the rat retina in vitro. AB - The effects of dopamine on the release of thyrotropin-releasing hormone (TRH) from the rat retina in vitro were studied. The rat retina was incubated in the medium 199 (pH 7.4) with 1.0 mg/ml of bacitracin and 100 micrograms/ml of ascorbic acid. The amount of TRH release into the medium was measured by radioimmunoassay. The TRH release from the rat retina was inhibited significantly in a dose-related manner with the addition of dopamine, but not with pimozide. The inhibitory effects of dopamine on TRH release from the rat retina were blocked with an addition of pimozide to the medium. The elution profile of methanol-extracted rat retina on sephadex G-10 was identical to that of synthetic TRH. From these findings it is concluded that the dopaminergic system inhibits TRH release from the rat retina in vitro. PMID- 1634192 TI - Role of the sympathoadrenal system in the regulation of glycogen metabolism in resting and exercising skeletal muscles. AB - The purpose of the present study was to characterize the role of catecholamines in the regulation of skeletal muscle glycogen metabolism during exercise. Using the rat hindlimb perfusion technique we have measured skeletal muscle glycogen content, glycogen phosphorylase and synthase activities in sympathectomized and/or demedullated rats under epinephrine treatment (10(-7) M) at rest and during muscle contraction. When epinephrine and/or norepinephrine deficiency was induced, muscle contraction resulted in a decrease in glycogen content (-63%) despite a decrease in glycogen phosphorylase activity ratio (0.25 to 0.11; p less than 0.001) and an increase in glycogen synthase activity ratio (0.13 to 0.27; p less than 0.001). Under these conditions, epinephrine treatment further reduced glycogen content while blunting the changes in the activity ratio of the rate limiting enzymes. These data indicate that catecholamines do not play a primary role in skeletal muscle glycogen breakdown during acute exercise and suggest that allosteric regulators may be of prime importance. PMID- 1634193 TI - The beta cell function in NIDDM patients with secondary failure: a three year follow-up of combined oral hypoglycemic and insulin therapy. AB - Eleven Type 2 (non-insulin-dependent) diabetic patients, islet cell autoantibodies negative, nonobese with secondary failure to oral hypoglycemic agents (OHA) [glyburide (7.5 mg/day) and phenformin (75 mg/day)] and HbA1c 10.2 +/- 0.6% were studied. Insulin receptors on circulating monocytes, glucose utilization at supraphysiological insulin concentrations, and plasma C-peptide after i.v. glucagon were evaluated before and after 2 months of combined therapy with OHA and insulin (Ultratard HM Novo). A significant improvement was demonstrated in HbA1c and glycemia after two months of treatment. Glucose MCR was increased after two months of treatment whilst basal C-peptide was decreased as well as receptor binding to monocytes. After three years of combined therapy, body weight, glycemia and HbA1c did not increase. After three years the C-peptide basal values were significantly increased with respect to values found after 2 months of therapy. These results demonstrate that insulin treatment may restore insulin sensitivity in NIDDM patients resistant to OHA treatment and that after three years there is no exhaustion of B-cell function. PMID- 1634194 TI - Enhanced cholesteryl ester transfer protein activities and abnormalities of high density lipoproteins in familial hypercholesterolemia. AB - Cholesteryl ester transfer protein may play a role in the cholesteryl ester metabolism between high density lipoproteins (HDL) and apolipoprotein B containing lipoproteins. To investigate relationship between HDL and cholesteryl ester transfer protein (CETP) activity in the development of atherosclerosis, the present study has focused on CETP activity in the patients with familial hypercholesterolemia (GH). HDL-C and HDL-C/apo A-I mass ratio in heterozygous FH were lower than those in normolipidemic controls. There was a 2-fold increase in total CETP activity in incubated FH serum compared with normolipidemic controls. Assays for CETP activity in the lipoprotein deficient serum (d greater than 1.215 g/ml) were carried out by measuring the transfer of radioactive cholesteryl ester from HDL (1.125 less than d less than 1.21 g/ml) to LDL (1.019 less than d less than 1.060 g/ml). CETP activities in heterozygous FH (79 +/- 4 nmol/ml/h) was significantly higher than those in normolipidemic controls (54 +/- 6 nmol/ml/h). The increased total cholesteryl ester transfer mainly results from increased CETP activity in the d greater than 1.215 g/ml, possibly reflecting an increase in CETP mass in serum. Increased CETP activity in the d greater than 1.215 g/ml was correlated positively with IDL-cholesterol/triglyceride mass ratio (r = 0.496, p less than 0.01), and negatively with HDL-cholesterol/apo A-I mass ratio (r = 0.334, p less than 0.05). These results indicate that the enhanced CETP activities may contribute to increase risk for developing atherosclerosis in FH by changing the distribution of cholesteryl ester in serum lipoproteins. PMID- 1634195 TI - Effects of probucol on plasma lipids, lipoproteins and parameters of high density lipoprotein metabolism. AB - Eight patients with primary hypercholesterolemia were treated with probucol for 17 weeks. Plasma total cholesterol, low density lipoprotein (LDL)-cholesterol, and high density lipoprotein (HDL)-cholesterol decreased by 16.6, 15.0 and 25.7%, respectively, in response to probucol treatment. Plasma levels of apolipoprotein B and apolipoprotein A-I also decreased, while apolipoprotein A-II concentrations were unchanged. The decrease in HDL-cholesterol levels was associated with a reduction in HDL particle size. No changes in the plasma lecithin:cholesterol acyltransferase activity or mass occurred in response to probucol treatment. In contrast, a significant 25% increase in plasma cholesteryl ester and triglyceride transfer activity occurred following probucol treatment. There was a positive correlation (R = 0.94) between cholesterol ester and triglyceride transfer. We propose that the increase in lipid transfer activity may in part explain the changes in HDL concentration and size, as well as the previously reported effect probucol has on reducing atherosclerosis in animal models. PMID- 1634196 TI - Effect of growth hormone (GH) on the promotion of body weight gain in the spontaneous dwarf rat: a novel experimental model for isolated GH deficiency. PMID- 1634197 TI - Microalbuminuria in obese subjects. PMID- 1634198 TI - Pseudoangiosarcomatous carcinoma: a clinicopathological study of seven cases. AB - Seven cases of carcinoma mimicking angiosarcoma occurring in skin (3 cases), breast (3) and lung (1) are described. The cutaneous, pulmonary and one of the breast carcinomas were poorly differentiated and squamous in type; the other two breast tumours were poorly differentiated ductal carcinomas with focal squamous differentiation. Histologically, the pseudoangiosarcomatous pattern was due to complex anastomosing channels and spaces lined by neoplastic cells. The spaces contained hyaluronic acid. The neoplastic cells exhibited cytokeratin positivity but yielded negative results with the endothelial cell markers, factor VIII related antigen and CD 34 (QB-END/10). Two breast tumours showed binding of UEA 1. Ultrastructurally, unequivocal epithelial differentiation was demonstrated in six of the cases. Pathogenetically, these tumours appeared to be variants of acantholytic squamous cell carcinoma. Recognition of this unusual form of carcinoma is important, as an incorrect diagnosis of angiosarcoma may lead to inappropriate treatment and prognostication. PMID- 1634199 TI - Cellular relationship impairment in maturation arrest of human spermatogenesis: an ultrastructural study. AB - Ultrastructural examination of testicular biopsies from cases of maturation arrest showed that there were characteristic abnormalities of the Sertoli cell junctional connections. These abnormalities together with the meiotic failure afford an explanation for the severe oligospermia or azoospermia noted in patients with maturation arrest. Premature setting up of ectoplasmic specializations in front of early spermatids and/or spermatocytes were also observed. PMID- 1634200 TI - Colloid cysts of the third ventricle: an immunohistochemical study. AB - Eleven colloid cysts of the third ventricle were investigated by immunohistochemistry using 16 mono- and polyclonal antibodies. Colloid cyst epithelium, choroid plexus epithelium and ependyma showed different immunohistochemical profiles. In particular, antibodies to different cytokeratins and to transthyretin revealed considerable and constant differences of immunoreactivity. Therefore, common derivation of the three tissues seems unlikely. Our findings are interpreted in favour of the non-neuroepithelial origin of third ventricular colloid cysts. PMID- 1634201 TI - Desmoplastic supratentorial neuroepithelial tumours of infancy. AB - The clinicopathological features of two infants with desmoplastic supratentorial neuroepithelial tumours are described. The cases were similar to the 26 cases reported previously as desmoplastic infantile ganglioglioma and superficial cerebral astrocytoma attached to dura. Neuronal differentiation was absent on routine stains, but was immunohistochemically established. We review the literature and suggest classifying this clinicopathological entity by using a general designation such as desmoplastic supratentorial neuroepithelial tumours of infancy, a term which indicates the variability in the amount and lines of differentiation. PMID- 1634202 TI - Differential expression of the HECA-452 antigen (cutaneous lymphocyte associated antigen, CLA) in cutaneous and non-cutaneous T-cell lymphomas. AB - The monoclonal antibody HECA-452 identifies an antigen that is primarily expressed on high endothelial venules, the preferred site of lymphocyte extravasation in lymphoid tissues, and also on a subpopulation of myelomonocytic cells and some T-cells. We investigated the expression of the HECA-452 antigen, also called the cutaneous lymphocyte associated antigen, in primary cutaneous and primary non-cutaneous T-cell non-Hodgkin's lymphomas. The tumour cells of cutaneous T-cell non-Hodgkin's lymphomas were positive in 53% of cases, while only 5% of the non-cutaneous lymphomas were positive. These differences were also present in morphologically identical tumours. Thus, the tumour cells in six out of 10 primary cutaneous anaplastic large cell T-cell lymphomas were positive, while they were positive in none of 24 primary non-cutaneous anaplastic large cell T-cell lymphomas. In general, primary cutaneous and primary nasal T-cell non Hodgkin's lymphomas were devoid of HECA-452 positive high endothelial venules, whereas most nodal T-cell non-Hodgkin's lymphomas contained HECA-452 positive high endothelial venules. These observations suggest that the HECA-452 antigen might be related to a skin-associated type of lymphoid tissue and to lymphomas originating in the skin. However, the results of HECA-452 expression in secondary sites, and the clinical data of the primary cutaneous large cell lymphomas did not support the concept that HECA-452 is functionally involved in homing to the skin, or that loss of the HECA-452 antigen is related to tumour progression of primary cutaneous T-cell lymphomas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634203 TI - Thymoma in childhood: a clinicopathological study of five cases. AB - The histological and clinical findings in five cases of thymoma arising in paediatric patients have been studied. The age range was 11-15 years and no patient was affected by myasthenia gravis. All tumours were macroscopically encapsulated, but two of them displayed evidence of microscopic capsular invasion. Histologically, four cases were of the predominantly cortical type (organoid thymoma) with prominent areas of medullary differentiation and Hassall's bodies; one case was of the cortical type. All patients are alive and disease-free 3 months to 9 years after surgery. These findings suggest that thymoma in the paediatric age group may be characterized by fairly uniform clinicopathological features, with a low rate of association with myasthenia gravis and a favourable prognosis. PMID- 1634204 TI - Malignant melanoma occurring in a case of oculocutaneous albinism. PMID- 1634205 TI - Pilomatrixoma or calcifying epithelioma of Malherbe invading bone. PMID- 1634206 TI - Malignant teratoma of the thyroid: case report and literature review of thyroid teratoma in adults. PMID- 1634207 TI - KP1 (CD68) staining of granular cell neoplasms: is KP1 a marker for lysosomes rather than the histiocytic lineage? PMID- 1634208 TI - Epithelioid angiosarcoma arising in an arteriovenous fistula. PMID- 1634209 TI - Diversion proctocolitis. PMID- 1634210 TI - Angiolymphoid hyperplasia with eosinophilia. PMID- 1634211 TI - Silver staining of nucleolar organizer regions in prostatic lesions. PMID- 1634212 TI - Data watch. 1990 physician inpatient revenues, admissions. PMID- 1634213 TI - New test? Hanlester decision clamps down on MD ventures. AB - What's the difference between inducement and encouragement? That's a key question in the Hanlester Network case. Attorneys and other experts are carefully sifting through the implications of Hanlester, and what its precise--and very important- effects may be on joint ventures with physicians. PMID- 1634214 TI - Great comebacks: the 1992 turnaround contest winners. AB - Turning a hospital around takes hard work, determination, and guts. The winners of this year's Hospital Turn-around of the Year Contest, sponsored by Hospitals and Coopers & Lybrand, demonstrate that a successful turn-around is about much more than money, and that it can't be judged a success based solely on financial results. The management team of each winning hospital showed imagination and courage in tackling their hospitals' problems. Congratulations to this year's winners and finalists for a job well done. PMID- 1634215 TI - Is new OIG physician fraud alert precursor to enforcement action? AB - A recent fraud alert published by the OIG listing "suspect hospital incentive arrangements" in physician recruitment practices is compelling hospital executives to review their recruitment strategies. "What is new about this fraud alert," says an attorney, "is that the OIG has put them into one document as an indication of its enforcement priorities." PMID- 1634216 TI - Health care for the homeless: what role should hospitals play? AB - A growing number of hospitals across the country are collaborating with others in their communities to provide health care to the homeless. "Hospitals should take a lead role" in this area, say those already involved. PMID- 1634218 TI - The AHA names 1992 award recipients. PMID- 1634217 TI - SDR 1992 Vendor Awards of Excellence. How hospital users rate application software. AB - Information systems budgets for 1992 increased among medium and large hospitals and decreased slightly among smaller facilities, according to data gathered by Shared Data Research (SDR), Hudson, OH, for its Third Annual Vendor Awards of Excellence program. PMID- 1634219 TI - High turnover in Congress clouds health issues. PMID- 1634220 TI - Coalition develops software to refer uninsured for care. PMID- 1634221 TI - 'Unwieldy' claims could bog down automation process. PMID- 1634222 TI - MAP (Multidisciplinary Apprentice Program): matching care-givers to patient needs. PMID- 1634223 TI - Management leadership critical to CQI success. PMID- 1634225 TI - Mild dominant osteogenesis imperfecta with intrafamilial variability: the cause is a serine for glycine alpha 1(I) 901 substitution in a type-I collagen gene. AB - The molecular defect responsible for a case of mild osteogenesis imperfecta (OI) with repeated femoral fractures was investigated. The proband and his mother, who presented minor OI signs but no bone fractures, were shown to produce normal and abnormal type-I procollagen molecules in their dermal fibroblasts. The molecular defect was localized in about half of the proband's pro alpha 1(I) mRNA molecules by chemical cleavage with piperidine of hydroxylamine-reacted mRNA:cDNA heteroduplexes. The corresponding region was reverse-transcribed and amplified by polymerase chain reaction (PCR). Cloning and sequencing of the amplified products revealed in both subjects a G-to-A transition in the first base of codon 901 of the alpha 1(I) triple helical domain, which led to a serine for glycine substitution. Allele-specific oligonucleotide hybridization to amplified genomic DNA from fibroblasts and leukocytes confirmed the heterozygous nature of both patients and proved the absence of mosaicism. The presence of the mutation was excluded in other healthy family members, who were reported to have bluish selerae. The mild phenotypic outcome of this newly characterized mutation contradicts previous findings on glycine substitutions in the C-terminal region of collagen triple helix, most of which caused lethal OI. PMID- 1634224 TI - Sex determination and sex reversal: genotype, phenotype, dogma and semantics. AB - The genetic terminology of sex determination and sex differentiation is examined in relation to its underlying biological basis. On the assumption that the function of the testis is to produce hormones and spermatozoa, the hypothesis of a single Y-chromosomal testis-determining gene with a dominant effect is shown to run counter to the following observed facts: a lowering in testosterone levels and an increase in the incidence of undescended testes, in addition to sterility, in males with multiple X chromosomes; abnormalities of the testes in autosomal trisomies; phenotypic abnormalities of XX males apparently increasing with decreasing amounts of Y-chromosomal material; the occurrence of patients with gonadal dysgenesis and XY males with ambiguous genitalia in the same sibship; the occurrence of identical SRY mutations in patients with gonadal dysgenesis and fertile males in the same pedigree; and the development of XY female and hermaphrodite mice having the same genetic constitution. The role of X inactivation in the production of males, females and hermaphrodites in T(X;16)16H mice has previously been suggested but not unequivocally demonstrated; moreover, X inactivation cannot account for the observed bilateral asymmetry of gonadal differentiation in XY hermaphrodites in humans and mice. There is evidence for a delay in development of the supporting cells in XY mice with ovarian formation. Once testicular differentiation and male hormone secretion have begun, other Y chromosomal genes are required to maintain spermatogenesis and to complete spermiogenesis, but these genes do not function effectively in the presence of more than one X chromosome. The impairment of spermatogenesis by many other chromosome abnormalities seems to be more severe than that of oogenesis. It is concluded that the notion of a single testis-determining gene being responsible for male sex differentiation lacks biological validity, and that the genotype of a functional, i.e. fertile, male differs from that of a functional female by the presence of multiple Y-chromosomal genes in association with but a single X chromosome. Male sex differentiation in XY individuals can be further impaired by a euploid, but inappropriate, genetic background. The genes involved in testis development may function as growth regulators in the tissues in which they are active. PMID- 1634226 TI - Microdeletions in interval 6 of the Y chromosome of males with idiopathic sterility point to disruption of AZF, a human spermatogenesis gene. AB - For males with idiopathic sterility, a molecular screen specific for small lesions (microdeletions) in interval 6 of the Y chromosome was set up using 29 Y DNA probes. A "de novo" microdeletion in Y interval 6 was detected in 2 out of 19 "chromosomally normal" sterile males. The first microdeletion includes the Y-DNA probes pY6HP35 and 12f3; the second microdeletion includes the Y-DNA probes pY6HP52, 49f, FR15-II and the subinterval "C" of probe 50f2. A probe of the pY6H sequence family is present in both deletions. Sequences of this family cross hybridize to dhMiF1, a DNA sequence of a fertility gene structure on the Y chromosome of Drosophila hydei. It was possible to map the position of the Y deletion of one patient to the distal part of Yq11.22 or the proximal part of Yq11.23, and the deletion of the second patient to the distal part of Yq11.23. These microdeletions probably do not overlap. Since AZF, a human spermatogenesis gene, has been mapped to Y interval 6, we postulate that the microdeletions detected in this chromosome region affect the functional DNA structure of the AZF gene. If this holds true, it is possible that the AZF locus, cytogenetically mapped to distal Yq11, contains two spermatogenesis genes (AZFa and AZFb) or a large gene structure comparable to the Y fertility genes of Drosophila. PMID- 1634227 TI - Detection of two missense mutations and characterization of a repeat polymorphism in the factor VII gene (F7). AB - The 3' portion of the coagulation factor VII gene, containing the activation and serine protease domains, was investigated in four subjects with factor VII deficiency by temperature gradient gel electrophoresis and sequencing of polymerase chain reaction (PCR) products. Molecules displaying an altered melting behaviour were detected in three subjects, and direct sequencing showed two mutations. A G-to-T transversion causing a missense mutation, Cys-310 to Phe, suppresses a disulphide bond conserved in the catalytic domain of all serine proteases. This mutation, which in the homozygous form causes a severe reduction in protease activity (4%), was found in two patients from different Italian regions. A G-to-A transition, which gives rise to a missense mutation, Arg-304 to Gln, and is associated with the factor VII padua variant, was found in the heterozygous form in a subject also affected by von Willebrand disease. Two polymorphic alleles, which differ in one repeat monomer element, were precisely mapped in a region spanning the exon-intron 7 border of the factor VII gene and studied in families with factor VII or X deficiency. PMID- 1634228 TI - Paternal selection favoring mutant alleles of the retinoblastoma susceptibility gene. AB - Penetrance and segregation rates of mutant Rb-1 alleles were assessed in all 51 members of eight kindreds with hereditary retinoblastoma by concomitant ophthalmologic examination and determination of seven intragenic restriction fragment length polymorphisms (RFLPs). Penetrance was in the range reported in the literature except for one family in which it was only 42.8%. However, the odds of transmitting a mutant Rb-1 allele from one generation to the next were 25:9 in this population, much above the Mendelian 1:1 ratio (P less than 0.025). This preferential transmission was discovered through the use of molecular information. Further analysis revealed that this distortion was due to preferential inheritance among children of male carriers (18:4, P less than 0.005). No difference from a 1:1 segregation ratio could be detected among the children of female carriers (7:5). These findings were consistent with a review of relevant data in the literature. PMID- 1634229 TI - Metabolism of GM1 ganglioside in cultured skin fibroblasts: anomalies in gangliosidoses, sialidoses, and sphingolipid activator protein (SAP, saposin) 1 and prosaposin deficient disorders. AB - Cultured skin fibroblasts from controls and patients with lysosomal storage diseases were loaded with GM1 ganglioside that had been labelled with tritium in its ceramide moiety. After a 65-h or 240-h incubation, a large percentage of this ganglioside remained undegraded in GM1 gangliosidoses, whereas in the other storage diseases studied, one of its metabolites accumulated by 2-4 fold relative to controls. Labelled GM2 ganglioside accumulated in 4 variants of GM2 gangliosidosis, whereas labelled GM3 ganglioside accumulated in sialidosis, galactosialidoses and sphingolipid activator protein 1 (SAP-1, saposin B) and prosaposin (saposin A, B, C and D) deficient lipidoses. The reduced degradation of GM3 ganglioside in the SAP-1 and prosaposin deficiencies was attributed to the deficient function of SAP-1. The prosaposin deficient cells also showed a reduced re-utilization of radioactive metabolites from GM1 ganglioside (i.e. sphingosine and fatty acid) for phospholipid biosynthesis compared with fibroblasts from the SAP-1 deficient patient or normal controls. This anomaly was ascribed to the previously shown defect in ceramide degradation in prosaposin deficiency. PMID- 1634230 TI - A non-alphoid repetitive DNA sequence from human chromosome 21. AB - A non-alphoid repetitive DNA from human chromosome 22, consisting of a 48-bp motif, shows homology to both G-group chromosomes in the gorilla, thus indicating the presence of additional repeat family members on further human chromosomes. Therefore, we screened a chromosome-21-specific cosmid library using this repetitive sequence from chromosome 22 (D22Z3). Some 40-50 cosmid clones were positive in tests for hybridization. One of the clones giving the strongest signals was digested with EcoRI/PstI, which we knew to cut frequently within the repeats; this resulted in fragments containing repeat units only. The fragments were subcloned into plasmid vector pTZ 19. Sequence-analysis of a 500-bp insert showed ten copies of a 48-bp repeat similar to D22Z3, with about 15% sequence deviation from the chromosome 22 consensus sequence. In situ hybridization of the newly isolated recombinant established its chromosome 21 specificity at high stringency. Physical mapping by pulsed field gel electrophoresis placed this new repeat in close vicinity to the chromosome 21 alphoid repeat. No cross hybridization with other mammalian genomes except for those of apes was observed. The locus has been designated D21Z2 by the Genome Data Base. A gel mobility shift assay indicated that this repetitive motif has protein-binding properties. PMID- 1634231 TI - Population cytogenetics of aphidicolin-induced fragile sites. AB - Chromosome fragile sites are inducible by aphidicolin in cultured human lymphocytes. To assess the frequency and distribution of these common fragile sites in the general population, a cytogenetic survey was performed on 126 subjects, 59 males and 67 females, whose age ranged from 1 day to 72 years. Common fragile sites, induced by aphidicolin, were widespread and showed a remarkably different sensitivity among individuals; age influenced the overall frequency of fragile sites. Moreover, both age and sex seemed to modulate the expression of specific fragile sites. In our population, the most common fragile sites were: 3p14, 16q23, Xp22, 6q26, 1p31, 4q31, 1p22, 7q22, 2q33, 3q27, 2q31, 7q32, 14q24, 10q22, 5q31, 2q37, 6p21. PMID- 1634232 TI - Characterization of a new mutation (R292G) and a deletion at the human uroporphyrinogen decarboxylase locus in two patients with hepatoerythropoietic porphyria. AB - A deficiency in the activity of uroporphyrinogen decarboxylase (UROD), the fifth enzyme of the haem biosynthetic pathway, is found in familial porphyria cutanea tarda (F-PCT) and hepatoerythropoietic porphyria (HEP). A new mutation (R292G) and a deletion have been found in a pedigree with two HEP patients (two sisters). The R292G mutation was not detected in 13 unrelated affected patients with F-PCT, so it appears to be uncommon. The possibility that the arginine 292 may participate at the active site of the enzyme is discussed. A summary of the 7 mutations/deletions found in the UROD gene with their frequency is presented. PMID- 1634233 TI - Evidence for genetic heterogeneity in hereditary hydronephrosis caused by pelvi ureteric junction obstruction, with one locus assigned to chromosome 6p. AB - Hereditary hydronephrosis (MIM 143400) is an autosomal dominant trait that causes unilateral or bilateral pelvi-ureteric junction (PUJ) obstruction. Linkage analysis was undertaken in 5 families with hereditary PUJ obstruction using the major histocompatibility complex locus as a test marker. The data as a whole supported a hereditary hydronephrosis locus on 6p. Maximal lod scores were 3.090 at a recombination fraction of 0.1 with full penetrance, and 2.486 at a recombination fraction of 0.1 with a penetrance of 90%. However, analysis of two point lod scores using the HOMOG program revealed significant evidence for genetic heterogeneity with one locus on 6p in 4 of the families, and a different locus in one family. After exclusion of this unlinked family, two point analysis gave a maximal lod score of 3.9 at a recombination fraction of 0.05 with full penetrance, and 4.2 at a recombination fraction of 0.0 with 90% penetrance. These data support the assignment of one of the loci for hereditary hydronephrosis to chromosome 6p. PMID- 1634234 TI - Absence of mutations in the promoter region of the low density lipoprotein receptor gene in a large number of familial hypercholesterolaemia patients as revealed by denaturing gradient gel electrophoresis. AB - Denaturing gradient gel electrophoresis (DGGE) was used in combination with the polymerase chain reaction (PCR) to detect sequence variations in the promoter region of the low density lipoprotein receptor (LDLR) gene. On the basis of calculated predictive melting properties we designed primers to amplify a 447-bp fragment of the promoter region from position -512 to -66, containing previously identified regulatory sequences. Using a primer with a GC-clamp in combination with restriction enzyme digestion, two melting domains could be analysed simultaneously. By oligonucleotide-directed mutagenesis artificial mutants were generated to optimize the conditions and to test the sensitivity of the method. All mutants were readily detected by electrophoresis in a 9% polyacrylamide gel containing a 10%-60% linear denaturing gradient. Using this method, we analysed DNA samples of 350 heterozygous familial hypercholesterolaemia (FH) patients. No mutations were detected, suggesting that mutations in the regulatory elements of the promoter sequence do not play a significant role in the etiology of FH. PMID- 1634235 TI - The interleukin-7 receptor gene is at 5p13. AB - A DNA probe for the interleukin-7 receptor gene was used for in situ hybridisation and Southern blot analysis of a series of rodent-human hybrid cell lines. The IL-7 receptor gene maps to 5p13. PMID- 1634236 TI - Novel promoter and splice junction defects add to the genetic, clinical or geographic heterogeneity of beta-thalassaemia in the Portuguese population. AB - In order to delineate the spectrum and the relative abundance of beta-globin gene defects causing thalassaemia in the Portuguese population, a representative sample was analysed including 51 beta-thalassaemia carriers along with 26 patients representing different clinical phenotypes. Seven mutations were identified, four of which [codon 39 (C----T), 39%; intervening sequence (IVS) 1 nucleotide (nt) 1 (G----A), 26%; IVS 1 nt 110 (G----A), 17%; IVS 1 nt 6 (T----C), 15%] account for 97% of 93 beta-thalassaemia chromosomes. Two previously undescribed mutations, namely a C----T substitution at position--90 in the proximal CACCC box, and the deletion of nucleotides 4 and 5 (AG) in IVS2 were identified. The uncommon, though ubiquitous, G----T transversion at codon 121 was found once upon haplotype V. Direct prenatal diagnosis can be offered to 95% of couples at risk of bearing a thalassaemic child. PMID- 1634237 TI - A novel mutation in the beta-protein coding region of the amyloid beta-protein precursor (APP) gene. AB - A novel mutation, a C to T transition at base pair 2124 in exon 17 of the amyloid beta-protein precursor (APP) gene, has been identified by direct sequencing of amplified DNA from two Alzheimer's disease (AD) patients. A simple oligonucleotide-hybridization procedure was developed to allow population studies of this DNA variation. The mutation, which is silent at the protein level, was present in 2 out of 12 investigated AD patients, in 1 out of 60 non-AD patients and in 1 out of 30 healthy individuals. The mutation can be used as a new marker for linkage studies involving the APP gene, although more comprehensive population studies are required to determine the status of the mutation as a possible risk factor for the development of AD. PMID- 1634238 TI - A single nucleotide substitution in the phosphoglycerate kinase (PGK)-1 gene occurred after the separation of PGK-1 and PGK-2. AB - The mammalian genome contains two functional loci for the production of phosphoglycerate kinase, PGK-1, an X-linked gene expressed in all somatic cells, and PGK-2, an autosomal intron-less gene expressed exclusively in late spermatogenesis. A nucleotide substitution from guanine to thymine was recently found at position 473 of PGK-1 mRNA in PGK Shizuoka. The mutation was not found in the PGK-2 gene and might have occurred after separation of PGK-1 and PGK-2. PMID- 1634239 TI - Masking in three-dimensional auditory displays. AB - The extent to which simultaneous inputs in a three-dimensional (3D) auditory display mask one another was studied in a simulated sonar task. The minimum signal-to-noise ratio (SNR) required to detect an amplitude-modulated 500-Hz tone in a background of broadband noise was measured using a loudspeaker array in a free field. Three aspects of the 3D array were varied: angular separation of the sources, degree of correlation of the background noises, and listener head movement. Masking was substantially reduced when the sources were uncorrelated. The SNR needed for detection decreased with source separation, and the rate of decrease was significantly greater with uncorrelated sources than with partially or fully correlated sources. Head movement had no effect on the SNR required for detection. Implications for the design and application of 3D auditory displays are discussed. PMID- 1634240 TI - Minimum audible movement angle as a function of the azimuth and elevation of the source. AB - In the future auditory directional cues may enhance situational awareness in cockpits with head-coupled displays. This benefit would depend, however, on the pilot's ability to detect the direction of moving sounds at different locations in space. The present investigation examined this ability. Auditory motion acuity was measured by the minimum audible movement angle (MAMA): the minimum angle of travel required for detection of the direction of sound movement. Five experienced listeners were instructed to indicate the direction of travel of a sound source (broadband noise at 50 dBA) that moved at a velocity of 20 deg/s. Nine azimuth positions were tested at 0 deg elevation. Five elevations were then tested at 0 deg azimuth. Finally two azimuth positions were tested at an elevation of 80 deg. The position of the source did not significantly affect the MAMA for azimuth locations between +40 and -40 deg and elevations below 80 deg. Within this area the MAMA ranged between 1 and 2 deg. Outside this area the MAMA increased to 3 to 10 deg. PMID- 1634241 TI - The effect of accommodation on retinal image size. AB - The apparent size of an object is diminished when accommodation of the eye moves inward to a position closer to the observer than to a viewed object. This phenomenon is called accommodation micropsia. Using schematic eyes, we investigated change in retinal image size caused by a change in accommodation. The use of schematic eyes is also discussed and is justified. The calculated magnitude of this diminution for four schematic eyes ranged from unity at infinity to a maximum of 0.98 (-2%) at about 12.0 diopters (D). For distances at which accommodation micropsia is typically observed (about 2.0 D), retinal minification is less than 0.997 (-0.3%). Thus changes in the size of the retinal image attributable to accommodation are virtually negligible when compared with the observed reduction of 3% to 33%. This suggests that accommodation micropsia is mediated almost entirely by processes other than those involving the optics of the eye. PMID- 1634242 TI - Apparent size and distance in an imaging display. AB - The size-distance invariance hypothesis suggests that the perceived size and the perceived distance of objects in a field viewed naturally are closely related. However, this relationship breaks down when scenes are viewed through high-power optical systems. When natural scenes are viewed through an imaging display of unity magnification, there is a reduction in their apparent size. This raises the question of whether the relationship breaks down when scenes are viewed through a low-power imaging display. A single-lens reflex camera was used as an imaging display that enabled subjects to vary the size of imaged real-world scenes. Judgments of size were found to vary with depth information in scenes and between monocular and binocular viewing, consistent with a previous finding, but judgments of distance did not vary significantly across either of these conditions. The results suggest that judgments of size and judgments of distance with imaging displays are not influenced uniformly by environmental and task variables. PMID- 1634243 TI - Judgments of change and proportion in graphical perception. AB - Subjects judged change and proportion when viewing graphs in two experiments. Change was judged more quickly and accurately with line and bar graphs than with pie charts or tiered bar graphs, and this difference was larger when the rate of change was smaller. Without a graduated scale, proportion was judged more quickly and accurately with pie charts and divided bar graphs than with line or bar graphs. Perception is direct when it requires simpler or fewer mental operations; we propose that perception of change is direct with line and bar graphs, whereas perception of proportion is direct with pie charts and divided bar graphs. The results are also consistent with the proximity compatibility principle. Suggestions for improving the design of graphical displays are given. PMID- 1634244 TI - Arthritis induced in rats with adjuvant oil is a genetically restricted, alpha beta T-cell dependent autoimmune disease. AB - Adjuvant arthritis in rats is usually induced by injection of mycobacterium tubercle cell walls suspended in various adjuvant oils such as Freund's incomplete adjuvant (FIA) or pristane. We have recently shown that injection of adjuvant oils without inclusion of mycobacterium tubercle cell walls triggers arthritis [oil adjuvant-induced arthritis (OIA)] in the DA rat strain. The OIA is a genetically restricted disease since only DA rats are susceptible while Lewis, DA-fostered Lewis and F1 (Lew x DA) rats are relatively resistant. Activated alpha beta T cells infiltrate the affected joints of adjuvant oil-injected DA rats and treatment with monoclonal antibodies to the alpha beta T-cell receptor abrogates development of arthritis. These findings show that alpha beta T-cell activation is a critical event in the development of OIA. PMID- 1634245 TI - Induction of IgE antibodies and T-cell reactivity to ovalbumin in rats colonized with Escherichia coli genetically manipulated to produce ovalbumin. AB - The immune response to ovalbumin (OA) and the bacterial antigens, lipopolysaccharide (LPS) and fimbriae were studied in conventional rats colonized from birth with an Escherichia coli strain producing OA. The colonized rats had developed IgE antibodies against OA, but not against the fimbrial or the LPS antigens from the E. coli at 2 months of age. At this time all rats were primed with OA given intracutaneously in Freund's complete adjuvant. Two weeks later the colonized rats showed a 35% greater delayed-type hypersensitivity (DTH) reaction to OA, measured as ear swelling, than the controls. Thus bacteria carrying antigens resembling potential allergens might aggravate, or participate in the induction of allergic symptoms. In addition such bacteria could be efficient vaccine vectors in protection against parasites. The study illustrates the importance of the mode of antigen presentation for the subsequent immune response. PMID- 1634246 TI - Antibody responses to the blood group antigen D in SCID mice reconstituted with human blood mononuclear cells. AB - Mice with severe combined immunodeficiency (SCID) were reconstituted with peripheral blood mononuclear cells (PBMC) obtained from D-negative individuals who had been sensitized to D-positive erythrocytes. Anti-D was spontaneously secreted in mice reconstituted with PBMC obtained from donors within 14 days of re-immunization with D-positive erythrocytes, but was not detected in murine plasma when mice were reconstituted with PBMC obtained from the same donors many years after sensitization, even though anti-D was still present in the serum of these donors. In the murine plasma the anti-D titres were not related to the total human immunoglobulin concentrations. SCID mice reconstituted with PBMC from some donors immune to D-positive erythrocytes (but not immunized within 34 days of donating the sample) made a recall response to the D antigen, which in some cases was maintained for at least 84 days. Depletion of adherent cells from the reconstituting PBMC reduced the total concentration of human IgG obtained. These results show that SCID mice reconstituted with human PBMC (Hu PBMC-SCID) can make a recall response to the D antigen which cannot be attributed to non-specific polyclonal B-lymphocyte activation, and that efficient antigen processing and presentation of the integral erythrocyte membrane D polypeptide occurs in the Hu PBMC-SCID model. PMID- 1634247 TI - Cytokine-induced differentiation of IgA B cells: studies using an IgA expressing B-cell lymphoma. AB - Cytokines such as interleukin-5 (IL-5) and transforming growth factor beta 1 (TGF beta 1) increase IgA production by heterogeneous populations of lipopolysaccharide (LPS)-activated murine B cells. We have used IgA expressing murine B-lymphoma cells CH12.LX.C4.4F10 (4F10) to define the activity of these and other cytokines on IgA secretion at the single-cell level, membrane IgA expression, IgA polymerization and cell growth. IL-5 as well as LPS significantly increases IgA secretion of 4F10 cells, whereas TGF beta 1, a cytokine known to stimulate isotype switching to IgA among surface IgM-bearing B cells, inhibits IgA secretion. When tested alone, IL-1 beta, IL-2, IL-4, IL-6 and interferon gamma (IFN-gamma) do not significantly alter IgA secretion. However, there is a synergistic increase in IgA secretion when 4F10 cells are co-stimulated with IL-5 and IL-4, while IFN-gamma inhibits IL-5-stimulated up-regulation of IgA secretion. In parallel with increased IgA secretion after cytokine stimulation, 4F10 cells display less membrane IgA. Increased J-chain steady-state mRNA levels after IL-5 or LPS stimulation are paralleled by increased mRNA levels for secreted IgA, but are not accompanied by alterations in the ratio of monomeric to polymeric IgA. IL-5 and LPS initially stimulated but later inhibited 4F10 cell proliferation suggesting an inverse relationship between proliferation and differentiation in this cell line. 4F10 cells are a useful model for the characterization of discrete aspects of IgA B-cell differentiation, since the secretory and membrane Ig and proliferative responses of this IgA B-cell line to cytokines and LPS appear to parallel those of freshly isolated murine B cells. PMID- 1634248 TI - Entamoeba histolytica alters arachidonic acid metabolism in macrophages in vitro and in vivo. AB - Entamoeba histolytica infections are associated with a state of transient suppression of cell-mediated immunity. Macrophages, the most important cells in host defence and control of invasive amoebiasis, in infected animals have been found to be deficient in effector functions and accessory cell potential. However, little is known of the cellular mechanisms responsible for the down regulation. This study investigated whether macrophage dysfunction in amoebiasis is associated with altered macrophage arachidonic acid (AA) metabolism. Resident peritoneal macrophages (PMO) from naive gerbils produced enhanced levels of prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) in response to live E. histolytica trophozoites, to diffusible excretory/secretory products released from live amoebae in millicells and to freeze-thawed soluble amoebic proteins that were inhibitable by indomethacin (INDO) and nordihydroguaiaretic acid (NDGA), respectively. In contrast to PMO from naive gerbils, PMO from animals with amoebic liver abscesses at 10, 20 and 30 days post-infection (p.i.) released high basal levels of PGE2 and LTC4. In response to zymosan stimulation, PMO from infected animals produced two- and fourfold less PGE2 and LTC4, respectively, as compared to uninfected controls. AMO showed high constitutive basal release of PGE2 and LTC4. In response to amoebic and zymosan stimulation, AMO at 10 days p.i. produced significantly higher levels of PGE2 than AMO at 20 days p.i., while AMO at 30 days p.i. were refractory to stimulation to produce higher than basal levels of PGE2. Early (10 days) and late (20-30 days) AMO were refractory to amoebic and zymosan stimulation for enhanced LTC4 release. Pretreatment of AMO with AA substrate restored optimal PGE2 and LTC4 biosynthesis, but the cells were generally unresponsive to zymosan stimulation to produce augmented levels of LTC4. These results strongly suggest that intrinsic or secreted products or both from E. histolytica can induce profound alteration of eicosanoid formation in cyclooxygenase and lipoxygenase pathways in macrophages from naive and infected animals and that AA metabolism by AMO is sequentially modified during the course of the disease. PMID- 1634249 TI - Tumour necrosis factor-alpha mediates ultraviolet light B-enhanced expression of contact hypersensitivity. AB - Acute, low-dose ultraviolet B radiation (UVB) impairs the induction of contact hypersensitivity (CH) to dinitrochlorobenzene (DNCB) in certain inbred strains of mice (termed UVB-susceptible), but not in others (termed UVB-resistant). By contrast, exposure of mouse ear skin to an identical regimen of UVB has been reported to exaggerate the expression of CH. Recently, tumour necrosis factor alpha (TNF-alpha) has been demonstrated to mediate the deleterious effects of UVB on CH induction, presumably through local release of TNF-alpha within UVB exposed skin. The present studies were conducted to determine whether TNF-alpha also mediates the exaggerated expression of CH induced by UVB radiation. It was found that TNF-alpha, injected intradermally at the ear challenge site, enhanced the expression of CH to DNFB in conventionally sensitized mice. Interestingly, TNF alpha was able to amplify the expression of CH in the ears of both UVB susceptible strains of mice, and UVB-resistant strains. However, anti-TNF-alpha antibodies neutralized UVB-enhanced CH in UVB-susceptible mice, but not in UVB resistant mice. These findings support the proposition that TNF-alpha, released from UVB-exposed epidermal cells, is a critical mediator of the effects of UVB radiation on induction and expression of contact hypersensitivity. The effects of UVB radiation, intradermal (ID) TNF-alpha, and/or epicutaneously applied DNFB on epidermal Langerhans' cells were also evaluated and compared. Whereas epicutaneously applied DNFB alone profoundly depleted the epidermis of Langerhans' cells, DNFB painted on UVB-exposed or TNF-alpha-treated skin was much less effective at eliminating normal appearing Langerhans' cells. These results suggest that one direct effect of TNF-alpha on Langerhans' cells may be to immobilize these antigen-presenting cells transiently within the epidermis. It is proposed that this immobilization has the paradoxical effect (a) of interfering with sensitization, by preventing hapten-bearing Langerhans' cells from migrating to the draining lymph node, while at the same time (b) of amplifying CH expression by lengthening the interval of hapten retention and presentation with the epidermis. PMID- 1634250 TI - The effect of cytokines and chemotactic agonists on the migration of T lymphocytes into skin. AB - The migration of lymphocytes and neutrophils into skin sites stimulated with chemotactic agonists or with cytokines known to induce leucocyte-endothelial adhesion molecules was examined in sheep. Lymphocytes, collected from efferent prefemoral lymph, labelled in vitro with [111In]oxine and reinjected intravenously, migrated in large numbers into delayed-type hypersensitivity (DTH) reactions elicited by purified protein derivative (PPD) and into sites stimulated with tumour necrosis factor-alpha (TNF-alpha) or interferon-gamma (IFN-gamma). In contrast, interleukin (IL)-1 alpha, a potent inducer of endothelial leucocyte adhesion molecule-1 (ELAM-1), caused moderate accumulation of [111In]lymphocytes at concentrations that induced intense accumulation of 111In-labelled neutrophils. The chemotactic agonists IL-8 and zymosan-activated plasma (ZAP) caused accumulation of very large numbers of neutrophils but only small numbers of lymphocytes, whereas platelet-activating factor (PAF) and leukotriene B4 (LTB4) failed to recruit lymphocytes into skin. IFN-gamma was the only mediator to recruit lymphocytes in preference to neutrophils into skin. The results suggest that those lymphocyte chemotactic agonists which lack the ability to induce adhesion molecules on endothelium play only a minor role in directing migration of lymphocytes into skin. Immunohistological examination of skin lesions confirmed the findings of studies with 111In-labelled lymphocytes and indicated that there was a tendency for CD4+ cells to outnumber CD8+ cells in infiltrates induced by all mediators. In contrast to the elevated numbers of T19+ subset of T-cell receptor (TcR+) gamma delta cells present in DTH reactions, none of the mediators induced migration of T19+ cells into skin. PMID- 1634251 TI - Natural killer (NK) cell activity in human long-term bone marrow cultures (LTBMC): effects of interleukin-2 (IL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF) on the progenitor cells. AB - Human bone marrow-derived progenitor cells were studied in a long-term bone marrow culture system (LTBMC) dependent on an autologous stroma cell layer. The establishment of the stromal cell layer was facilitated by using marrow obtained from small pieces of sternum, which was cultured for 4 weeks without addition of exogenous growth factors. After this period, the response of LTBMC to two different cytokines [recombinant human interleukin-2 (rhIL-2) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF)] was investigated. Our results show proliferation in response to both cytokines and induction of differentiation of cells able to bind IL-2 and/or GM-CSF again. The two cytokines also generate cells responding to rhGM-CSF by colony formation. However, a difference with respect to morphology, phenotype and cytotoxic function of cells in the LTBMC, was noted between the two cytokines. Cells with large granular lymphocyte (LGL) morphology and cytotoxic activity against K562 and Daudi were generated only in the rhIL-2-supplemented LTBMC. This was compatible with a higher frequency of cells expressing the CD56+ phenotype in the IL-2-stimulated LTBMC as compared to the GM-CSF supplemented LTBMC. Our results also demonstrate the existence of a population of myeloid progenitor cells (CD33+) with ability to bind IL-2 in fresh bone marrow (BM). PMID- 1634253 TI - Selection of BoCD25 monoclonal antibodies by screening mouse L cells transfected with the bovine p55-interleukin-2 (IL-2) receptor gene. AB - The bovine interleukin-2 receptor-alpha (IL-2R alpha) gene has been isolated and a rabbit antiserum against a fusion protein of the gene has been produced. However, the antiserum does not inhibit IL-2-dependent proliferation. Since a panel of monoclonal antibodies (mAb) to bovine activation antigens was available, we transfected the gene into mouse L fibroblasts, selected stable transfectants with the rabbit antiserum, and screened for antibodies that bound the transfected cells but not the untransfected cells. Three mAb were selected and all three precipitated a molecule of M(r) 55,000 (under reducing conditions) from activated cells, as expected from homology with mouse and human IL-2R alpha (CD25, Tac). One of the three mAb was a strong inhibitor of IL-2-dependent proliferation of bovine lymphocytes. Thus, the availability of transfected cells allowed us to establish quickly and unequivocally the antigenic specificity of a number of antibodies. PMID- 1634252 TI - Modulation of in vitro porcine natural killer cell activity by recombinant interleukin-1 alpha, interleukin-2 and interleukin-4. AB - In order to understand better how cytokines modulate porcine lymphocyte-mediated natural cytotoxicity and to develop a rapid and reliable colorimetric assay to study that activity in young pigs, we studied inherent and cytokine induced in vitro natural killer (NK) activity. The cytokines we studied were human recombinant interleukin-1 alpha (IL-1 alpha), IL-2, IL-4 and interferon-gamma (IFN-gamma). Natural killer activity by peripheral blood mononuclear cells (PBMC), reported as per cent specific lysis (%SL), was determined by the colorimetric measurement of lactate dehydrogenase released from tumour cell targets, YAC-1 and K562. Inherent NK activity was low and remained relatively unchanged by alterations of assay length or effector cell concentration. Low NK activity was also observed in response to IL-4 and IFN-gamma. IL-2 and, to a lesser extent, IL-1 alpha induced significant NK activity with trends towards increasing %SL with increasing cytokine dose. Optimal IL-1 alpha- and IL-2 induced NK activity could be observed at 18 hr, with significant activity stimulated by IL-2 as early as 4 hr. IL-2-induced NK activity was sensitive to effector cell concentration; %SL decreased as the effector to target ratio decreased. IL-1 alpha- and IL-2-induced NK activities were decreased in the presence of IL-4. These results indicate porcine PBMC are sensitive to in vitro modulation by human recombinant IL-1 alpha, IL-2 and IL-4. The ability of IL-1 alpha and IL-2 to induce swine NK activity and the ability of IL-4 to inhibit that activity are similar to the actions of those cytokines in human NK systems. PMID- 1634255 TI - Surface expressed heat-shock proteins by stressed or human immunodeficiency virus (HIV)-infected lymphoid cells represent the target for antibody-dependent cellular cytotoxicity. AB - The expression of heat-shock proteins (HSP) of the 72,000 MW family by Daudi and H9 lymphoma cells has been investigated by flow cytometry. It has been found that both heat-stressed and chronically human immunodeficiency virus (HIV)-infected lymphomas show an increased expression of heat-shock proteins (HSP). Moreover, murine monoclonal antibody (mAb) against 72,000 MW HSP was able to mediate antibody-dependent cellular cytotoxicity (ADCC) using peripheral blood lymphocytes (PBL) as effector cells. All target cells used in these experiments were efficiently lysed in the presence of anti-HSP antibody suggesting a role of membrane HSP in the elimination of stressed or infected cells. PMID- 1634254 TI - Identification of immunosuppressive fractions from the rat submandibular salivary gland. AB - It had previously been suggested that the submandibular gland (SMG) of mice and rats may contain in vivo immunosuppressive factor(s). To identify such factor(s), we used a multi-step purification procedure of rat SMG extracts. Gel filtration chromatography of the SMG crude extract resulted in two pools of fractions with significant effects on lymphocyte reactivity in the in vitro concanavalin A (Con A) bioassay. Of these two pools, only the one with lower molecular weight resulted in the prolongation of murine skin allograft survival, the suppression of the delayed-type hypersensitivity (DTH) response to picryl chloride and the decrease in number of direct (IgM) plaque-forming cells against sheep red blood cells. Fractionation of this low molecular weight (LMW) pool through hydrophobic interaction chromatography resulted in three protein fractions designated A, B and C. Of these fractions only fraction A produced significant suppression of the DTH response. Further purification of fraction A with anion exchange chromatography produced two fractions with immunosuppressive activity in the DTH response. One fraction demonstrated on SDS-PAGE a single component of 40,000 MW, while the other had two components of 30,000 and 40,000 MW respectively. PMID- 1634256 TI - Interferon-gamma-dependent immunosuppressive effects of human gingival fibroblasts. AB - Immunoregulatory functions of human gingival fibroblasts (HGF) were examined. As in fibroblasts isolated from other tissues, HGF were activated with interferon gamma (IFN-gamma) to express HLA-DR molecules. Despite the fact that the IFN gamma-treated HGF showed phenotypical resemblance to so-called antigen-presenting cells (APC), the IFN-gamma-treated HGF were ineffective stimulators of alloreactive peripheral T cells. Conversely, IFN-gamma-treated HGF dramatically inhibited the proliferative responses of allogeneic APC (allo-APC) or phytohaemagglutinin (PHA)-stimulated T cells. Immunosuppressive effects of culture supernatant (CS) of IFN-gamma-treated HGF were low and were completely abrogated by the addition of indomethacin. Moreover, the production of prostaglandin E2 (PGE2) by HGF was not affected by IFN-gamma. These results suggest that IFN-gamma-dependent immunosuppressive effects of HGF were not due to PGE2 produced by HGF. In order to investigate further the mechanism(s) of IFN gamma-dependent immunosuppressive effects of HGF, activated T cells and IFN-gamma treated HGF were separately cultured in the same well by collagen films which were assembled in cylindrical cells and disturbed physical interactions between T cells and HGF. The proliferative responses of T cells which directly contacted with IFN-gamma-treated HGF were inhibited more significantly than those of T cells which did not contact with IFN-gamma-treated HGF. This suggests that IFN gamma-dependent immunosuppressive effects of HGF were mediated by direct interactions between T cells and activated HGF. The present results suggest that IFN-gamma-stimulated HGF would modulate the immune responses of locally infiltrated T cells in periodontal lesions. PMID- 1634257 TI - A view of the workshop. PMID- 1634258 TI - Dutch information policies in the near future. AB - The Dutch Ministry of Welfare, Health and Culture played an important part in Picture Archiving and Communicating Systems (PACS)-related activities in the Netherlands. It subsidized a large Dutch PACS project, which took place in the period 1986-1989. Moreover the ministry subsidized this workshop on the Technology Assessment of PACS. In this paper, the Director of the Information Policy department of the ministry explains the backgrounds of Dutch policy in the support of development and evaluation of information technologies applied in the health care sector in general and, more specifically, of PACS. PMID- 1634259 TI - Workshop aims, outline of the program. AB - This workshop on the Technology Assessment of PACS has been organized as a rounding off of the Technology Assessment activities which were initiated within the Dutch PACS Project (1986-1989). It is made possible by a funding from the Dutch Ministry of Health Care (WVC). We hope it will be not only a rounding off, but will contribute to more intensive cooperations in this area. In the scope of the Dutch PACS project, the software package CAPACITY for cost analyses of PACS has been developed, to stimulate the dialogue and exchange of data. During the workshop, the data which were collected with CAPACITY are used as a framework for discussions. This paper presents the outline of the workshop, its background, its aims and the program. PMID- 1634260 TI - Overview of CAPACITY data. AB - This paper presents an overview of the data from 15 cases collected with the CAPACITY software for cost analysis of PACS. The data suggest that both hospital wide and partial PACS implementations do not pay back yet. Only Nuclear Medicine PACS systems may be introduced cost-neutral in the near future. Because of the assumed price drop of hardware components of 5-25% per year, hospital wide and partial PACS may allow cost savings within the next 10-20 years. There are major differences in viewpoints concerning the required PACS configurations and their costs. The experiences with the CAPACITY software suggest the need for the establishment of key rules, for designing a PACS configuration and for estimating PACS costs. PMID- 1634261 TI - Overview of some methodological problems in assessment of PACS. AB - The purpose of technology assessment of picture archiving and communications systems (PACS) is to establish the need for the technology, provide a measure of functionality and to establish the costs and benefits associated with the introduction of the system. Given concerns about the clinical acceptability of PACS, it is unlikely that radiologists will change from existing film based systems until a clear demonstration of costs and benefits has been performed. The major need at present is to quantify the benefits which may flow from the introduction of PACS system in a standard manner which can be accepted by all parties involved. PMID- 1634262 TI - Required functionality of PACS from clinical point of view. AB - Concerning the required functionality of PACS from a clinical point of view this paper describes the functionality during the several phases of the imaging process. A list of general requirements is summarized. To get more information a period of prototype development and testing is needed. During this period the required functionality has to be investigated by questionnaires and automatic registration by the work stations. PMID- 1634263 TI - Current views on the functionalities of PACS. AB - The concept of PACS has evolved from a central storage of medical images to a distributed data and image management system. The trend and evolution of the definition and design of PACS systems is described in this paper. Special emphasis on the concept of distributed and open architecture is given with a discussion of the advantages and disadvantages of each approach. A hospital-wide PACS system designed based on a distributed architecture integrated with a Hospital Information System (HIS) at the University Hospital of Geneva is further described. PMID- 1634264 TI - The impact of standards. AB - The development of standards in the field of PACS is essential. This paper explains why and describes the current activities in this field. Special emphasis is put on the European activities, i.e. the CEN/TC251 committee. The impact of standards is given on the relation between the Information Technology and Medical Imaging market. PMID- 1634265 TI - Legal aspects of picture archiving and communications systems. AB - Legal issues of PACS have so far received little attention. This paper gives an overview of this field. It distinguishes three problem areas: Property Law, Liability and Fair Information Practices. Current EC developments are described. PMID- 1634266 TI - A view from the Nijmegen PACS project. AB - A view on PACS is given from a radiology department involved in PACS as part of its medical research environment. Special attention is payed to historical developments in medical imaging to study the context of actual PACS developments. Some directions of future diagnostic developments are indicated. Both image data acquisition and presentation techniques are of interest to medical as well as industrial applications. It is pointed out how PACS is thought to depend on contextual factors. PMID- 1634267 TI - Methodology for the evaluation of diagnostic image quality. AB - This paper explains the theoretical backgrounds of various methods for the evaluation of diagnostic image quality. It introduces the Receiver Operating Characteristics (ROC) methodology. The major prerequisites, some important features of the experimental set-up and of the data analysis of an ROC study are explained. Dedicated software packages to support ROC studies are introduced. A possible method on how to relate image quality and cost-effectiveness is presented. Finally some current problems of the ROC method and possible improvements are discussed. PMID- 1634268 TI - The impact of PACS on the information flow. AB - It is likely that changes in hospital operational practices made possible by the introduction of a whole hospital PACS will require the present information and data patterns to be changed significantly. Some of the factors which will affect the flow of data and information are considered, and the implications of comparing the costs of installing 'whole hospital' PACS systems in different institutions are discussed. PMID- 1634269 TI - Evaluation of personnel savings through PACS: a modelling approach. AB - The ability to improve the efficiency of the use of medical image information is often believed to be one of the most important potentials of PACS. The organization within hospitals is however complex, which makes it difficult to predict the impact of the system. This paper addresses several methods for the analysis of the organizational impact and proposes a modelling method. PMID- 1634270 TI - Evaluation of PACS-induced organizational change. AB - Filmless digital imaging with a PACS will affect health care institutions by changing the handling of clinically relevant information, altering needed staffing levels, and possibly affecting both the quality and cost of care. Economic evaluation of PACS compares the costs and/or benefits of PACS with those of all other relevant alternatives. Other evaluations may focus on narrower research questions. This paper discusses methodological considerations in economic evaluation, methods of time measurement, and the methods and results of several applied assessments of PACS effects on the medical imaging department or the hospital. PMID- 1634271 TI - Quality assurance issues and PACS. AB - Quality assessment and assurance is a growing concern in all areas of health care. The concern is fueled by a body of evidence that indicates that quality of care is not optimal, and in many instances, is unacceptably low. Although different standards for quality have been proposed, health outcome is the ultimate standard, since improving health is the goal of the health care system. The effects of PACS on health outcome are not known. A PAC system has the potential to improve quality, especially if it makes the diagnostic process more efficient, but evidence that such improvement actually occurs is so far lacking. PMID- 1634272 TI - Administrative and organization impact of PACS and its effect on the quality of care. AB - PACS integrated to RIS and HIS will have a significant impact on the hospital operation. This paper describes the current radiological process and indicates at what points PACS may prove to be important, in order to guarantee its successful implementation with the objective to improve patient care by better management of personnel, equipment and information. PMID- 1634273 TI - The impact of PACS on research and education. AB - Picture Archiving and Communication Systems (PACS) are rapidly evolving and the total digital radiology department may be a reality within the next decade. PACS can have a major impact on the educational and research responsibilities of a medical institution. The possibility of correlating real patient data with existing radiological teaching files opens up numerous possibilities. Multi institutional research can be strengthened by employing the PACS as the means to the end. This paper discusses the representative examples of how teaching and research can be enhanced with PACS and the technical requirements to achieve the inter-connectivity. PMID- 1634274 TI - Influence of health care systems on the market for picture archiving and communication systems. AB - An analysis is given of the relation between health care systems and the PACS market. Two driving forces exist in the market: quality and price. It is argued that the quality driven market is mainly independent of the health care system and will be the force that drives the introduction of the health care system and will be the force that drives the introduction of PACS in the forthcoming years. Finally a change of focus is suggested from only archiving and communication to a more general concept of image networking, serving more goals than only the goal of working filmlessly. PMID- 1634275 TI - Experience with an operational nuclear medicine PACS in the Utrecht University Hospital. AB - At the department of nuclear medicine of the University Hospital Utrecht a single modality PACS has been operational since mid 1990. After 1 year of operation the functionality, the organizational and economical consequences and the acceptability of the PACS are evaluated. The functional aspects reviewed are: viewing facilities, patient data management, connectivity, reporting facilities, archiving, privacy and security. It is concluded that the improved quality of diagnostic viewing and the potential integration with diagnosis, reporting and archiving are highly appreciated. The many problems that have occurred during the transition period, however, greatly influence the appreciation and acceptability of the PACS. Overall, we feel that on the long term there will be a positive effect on the quality and efficiency of the work done in our department. PMID- 1634276 TI - PACS clinical experience at Georgetown University. AB - Georgetown University Hospital has been operating an image management and communications system (IMACS or PACS) for 3.5 years. This work was initially funded under the Army Medical Research and Development Command Digital Imaging Network Systems (DINS) project. The system was taken from a research system supporting only radiology tasks to one extended to clinical use, and has been used in clinical work for 3 years. This paper will summarize our PACS clinical experience and will describe the operational features implemented and those still necessary. PMID- 1634277 TI - Feasibility of PACS based on 2 years experiences of Hokkaido University PACS. AB - Some features of HU-PACS which is now just 2 years old are described with the results of clinical assessment on it. It is clear that many advancements in technology have made the HU-PACS to be a useful tool of clinical routines. The paper describes also problems of the system in future with general comments on technology assessment and cost benefit issues. PMID- 1634278 TI - PACS experiences in Trieste. AB - The installation of a commercial PACS in the Hospitals of Trieste has been the start-point for a project of technology assessment, aimed at the evaluation of technical, clinical and economic aspects related to the introduction of this new and expensive technology in the health care system. During more than two years of use of this system in the clinical environment, several research activities have been carried out concerning the analysis of the organization of radiology departments in Italy, the analysis of work and data volumes, the evaluation of technical and clinical performances of PACS versus conventional film-based radiology, the integration between PACS and RIS, the experimentation of teleradiology applications. An overview of the most important activities and related results is given in this paper as well as some indications about future developments of the Trieste Project. PMID- 1634279 TI - Benefits of coordinated action in PACS evaluation. AB - PACS, a health care technology still in its developmental stage, aims to improve the management of diagnostic imaging investigations. As the technology has not been comprehensively assessed, data and facts to justify its clinical, economic and other benefits are to date insufficient. Through internationally coordinated action, it is expected to obtain a faster and more comprehensive technology assessment of PACS as well as recommendations for optimization of the system and guidelines for its rational use in various health care environments. PMID- 1634280 TI - Opportunities for cooperation in the domain of informatics and telecommunications applied to health. AB - The European Community (EC) plays an important part in the stimulation of coordinated Research and Development activities in Europe. This paper describes features of the EC framework programmes, and gives an overview of the opportunities for the support of activities in Technology Assessment of PACS. PMID- 1634281 TI - Healthcare informatics and telecommunications: opportunities for international coordinated action. AB - The interest in international cooperation in the applications of telecommunications technologies to healthcare is growing. This paper gives an overview of current worldwide activities and suggests opportunities for the future. PMID- 1634282 TI - Study of the relationships between weather conditions and the marathon race, and of meteorotropic effects on distance runners. AB - The relationships between the results of Beijing International Marathon Races and the corresponding weather conditions are analysed quantitatively. There are obvious interrelationships between the marathon results and weather factors such as air temperature, wet bulb temperature and human biometeorological indices. For example, the correlation coefficient between the average times of the top ten finishers and temperature is r = 0.8910. The meteorological conditions are classified into three categories, suitable, moderate and unsuitable for running a marathon race, and the optimum meteorological index is given. Also the concept of a meteorological result, i.e. the part of the actual performances fluctuating with the changes in weather conditions, is presented. This plays an important role in some kinds of sports such as marathon racing. Finally, the results of physiological tests are given, which illustrate the physiological reactions of long- and middle-distance runners to the surrounding temperature. PMID- 1634283 TI - Environmental profile and critical temperature effects on milk production of Holstein cows in desert climate. AB - The environmental profile of central Arizona is quantitatively described using meteorological data between 1971 and 1986. Utilizing ambient temperature criteria of hours per day less than 21 degrees C, between 21 and 27 degrees C, and more than 27 degrees C, the environmental profile of central Arizona consists of varying levels of thermoneutral and heat stress periods. Milk production data from two commercial dairy farms from March 1990 to February 1991 were used to evaluate the seasonal effects identified in the environmental profile. Overall, milk production is lower during heat stress compared to thermoneutral periods. During heat stress, the cool period of hours per day with temperature less than 21 degrees C provides a margin of safety to reduce the effects of heat stress on decreased milk production. Using minimum, mean and maximum ambient temperatures, the upper critical temperatures for milk production are 21, 27 and 32 degrees C, respectively. Using the temperature-humidity index as the thermal environment indicator, the critical values for minimum, mean and maximum THI are 64, 72 and 76, respectively. PMID- 1634284 TI - Effects of running training on in vitro brown adipose tissue thermogenesis in rats. AB - Brown adipose tissue (BAT) is a major site of nonshivering thermogenesis (NST) during cold acclimation for most mammals. Repetitive nonthermal stress such as immobilization has been shown to enhance the capacity of NST as cold acclimation. In the present study, the effects of running training, another type of nonthermal stress, were investigated on in vitro thermogenesis and the cellularity of interscapular BAT in rats. The rats were subjected to treadmill running for 30 min daily at 30m/min under 8 degrees inclination for 4-5 weeks. In vitro thermogenesis was then measured in minced tissue blocks incubated in a Krebs Ringer phosphate buffer containing glucose and albumin at 37 degrees C, using a Clark type oxygen electrode. The trained rats showed less body weight gain during the experiment. The weights of BAT and epididymal white adipose tissue were smaller in the trained rats. Noradrenaline- and glucagon-stimulated oxygen consumption were also significantly smaller in the trained rats. The tissue DNA level was greater in the trained rats, but the DNA content per tissue pad did not significantly differ. The results indicate that running training reduces BAT thermogenesis, possibly as an adaptation to conserve energy substrates for physical work. PMID- 1634286 TI - Non-psoralen treatment of vitiligo. Part I. Cosmetics, systemic coloring agents, and corticosteroids. PMID- 1634285 TI - Eosinophilia-myalgia syndrome. PMID- 1634287 TI - Signal transduction in normal and psoriatic epidermal cells. PMID- 1634288 TI - Les grattinages de papier. PMID- 1634289 TI - Donovanosis (granuloma inguinale) still exists. PMID- 1634290 TI - Cutis marmorata telangiectatica congenita. AB - The authors describe ten cases of cutis marmorata telangiectatica congenita (CMTC). All of these cases were sporadic. The incidence of associated anomalies was relatively low, and three patients had skin manifestations (cutaneous atrophy and nevus telangiectaticus). In two patients, the right leg was shorter and thinner. Another two showed neurologic symptoms without lasting neurologic damage. New associated anomalies, such as tendinitis stenosans and bowing of the lower legs, did not provide additional information regarding the cause of CMTC. The authors suggest that Happle's lethal gene hypothesis for Klippel-Trenaunay and Sturge-Weber syndromes also could be applied to CMTC. PMID- 1634291 TI - Occupational or extrinsic stimulation factors and initial signs of progressive systemic sclerosis. AB - Forty-eight patients with progressive systemic sclerosis (PSS) (man-woman ratio, 7:41) were studied, and detailed questionnaires were used to clarify the relationship between occupational stresses and the initial signs of PSS. All of the patients were right-handed. Raynaud sign was seen in 37 of the 48 patients (77.1%) as the predominant initial sign of PSS, and it first was noticed on the right index and middle fingers. Three sets of extrinsic aggravating factors, vibration stress, fine hand work with mental stress, and exposure to cold, were believed to be related closely to the development of the initial signs because the initial signs appeared after long-term exposure to the extrinsic factors. PMID- 1634292 TI - Cutaneous lupus erythematosus in India: immunofluorescence profile. AB - The clinical profile and cutaneous lesions of 65 patients with lupus erythematosus (LE) are described. This included 28 discoid LE (13 disseminated, 15 localized), five subacute cutaneous LE, and 32 systemic LE. The need to recognize a pigmented macular form constituting 25% of discoid LE is emphasized. Increased incidence of involvement of the lower lip in discoid LE and pigmentation in systemic LE is noted. Lupus band test was found to be highly sensitive; it was positive for lesional skin of all untreated patients with subacute cutaneous LE and systemic LE, it was, however, not useful on nonlesional skin. PMID- 1634293 TI - Acute cutaneous graft versus host disease: a clinicopathologic and immunophenotypic study. AB - Acute graft versus host disease (GVHD) is a major complication of bone marrow transplantation. This study was undertaken to characterize the histopathologic alterations in early lesions of GVHD and to improve our understanding about the disease process. Histopathologic and immunoperoxidase studies of skin tissue were carried out in 20 patients of GVHD. Sixty percent had grade II histopathologic changes in the skin, grade I and III changes were observed in 35% and 5% respectively. Follicular involvement could be observed in all cases beyond grade I. Immunoperoxidase study revealed OPD4 (+) (T-helper) cells in dermis and OPD4 ( ) (probably cytotoxic/suppressor) cells in epidermis. PMID- 1634294 TI - Extensive macular amyloidosis associated with poikiloderma. PMID- 1634295 TI - Cutaneous cryptococcosis mimicking Kaposi's sarcoma as the initial manifestation of disseminated disease. PMID- 1634296 TI - Xanthoma disseminatum. PMID- 1634297 TI - Fatal disseminated Mycobacterium marinum infection. PMID- 1634298 TI - Senior medical student clinical and research electives in dermatologic surgery. AB - Five senior medical students enrolled in the 4 week clinical elective in dermatologic surgery and cutaneous oncology (DSCO); two of these students also enrolled in a 4 week research elective in DSCO. During the elective(s) the students made significant improvement in the six areas of clinical diagnosis, histopathologic diagnosis, clinical management, DSCO procedures, research skills, and general information about the subspecialty. Following their elective(s), these students submitted a total of six abstracts, one letter, and seven manuscripts for presentation or publication. PMID- 1634299 TI - Origin of the nevus cell: a retrospective. PMID- 1634300 TI - Glandular basement membrane zone immunofluorescence in cicatricial pemphigoid. PMID- 1634301 TI - Sweet's syndrome associated with multiple myeloma. PMID- 1634302 TI - Eczema herpeticum induced by sun exposure. PMID- 1634303 TI - The effect of dietary intake of fruits and vegetables on the odds ratio of lung cancer among Yunnan tin miners. AB - All newly diagnosed cases of lung cancer (N = 183) among male tin miners of Yunnan Province, China and age-sex matched occupational controls (N = 183 aged 45 79 years) were interviewed within 3 months following cancer diagnosis. The questionnaire included information about usual adult diet as well as employment and smoking histories. Over 95% of cases and controls were current smokers. The 27-item food frequency questionnaire included 11 fruits and vegetables rich in vitamin A and/or carotenoids. The effect of dietary intake of fruits and vegetables on risk of lung cancer was examined with adjustment for exposures to radon, arsenic, and smoking as previously documented risk factors for lung cancer. Tin miners with reduced intake of yellow and light green vegetables had statistically significant increased odds ratios (OR) of lung cancer (OR = 2.26 and OR = 2.39 for the lowest two quartiles of intake; P value for trend = 0.02) among cases compared with controls after multiple logistic regression adjustment for covariates; and this relationship was monotonic. Tin miners with reduced intake of tomatoes had statistically significant increased adjusted OR of lung cancer (OR = 2.64, OR = 3.09, OR = 2.36 for the three lowest quartiles of intake; P value for trend = 0.04). This is the first study to demonstrate a protective effect of vegetable intake versus the strong effects of smoking and occupational exposures on lung cancer risk. PMID- 1634304 TI - Influence of migrants on regional variations of stomach and colon cancer mortality in the Western United States. AB - In order to examine the impact of migrants on regional variations in stomach and colon cancer, standardized mortality ratios (SMRs) were calculated for the total, nonmigrant (born and dying in same state), and migrant (born out of state) White residents of each of the 11 western states in the United States (US). The SMRs were derived from the National Center for Health Statistics' Mortality Detail Files for 1979-1981 and the 1980 Census Public Use Microdata 5-Percent Sample tapes. Migrants in the western US accounted for 79% of all stomach and colon cancer deaths. There was no consistent relationship between the SMRs of migrants and nonmigrants, with the migrant SMRs being higher in some states and lower in others. As a consequence of this differential impact, and their substantial numbers, migrants obscured the underlying regional patterns of mortality risk observed in the nonmigrants. The states of high or low risk were more contiguous in the analysis based on nonmigrants than the total population, and the interstate ranges in mortality were greater for nonmigrants. In areas with high in-migration, mortality atlases based on the total population may give an inaccurate portrayal of regional mortality risks, and spurious correlations may arise between the distributions of diseases and environmental characteristics of the regions. Regional mortality patterns of nonmigrants may more precisely reflect the factors which are influencing these cancers and thus provide a greater potential in providing clues to their aetiologies. PMID- 1634305 TI - Occupation and hospitalization with ischaemic heart diseases: a new nationwide surveillance system based on hospital admissions. AB - A cohort of all people in Denmark aged 20-59 years on 1 January 1981 was followed up for four years for emigration, death and hospital admission for ischaemic heart disease (IHD) as the primary diagnosis. The data set allows tabulation of rates of hospitalization by occupation, position and industry. Well-known classic associations for IHD have been reproduced. Examples are: male bus drivers had a standardized hospitalization ratio (SHR) of 136; for male urban bus drivers SHR = 143, male taxi drivers SHR = 168, fishermen SHR = 129, men occupied in hotels and restaurants SHR = 140, women in hotels and restaurants SHR = 157. The consistency with previous findings is an argument that new significant associations should be treated as substantiated hypotheses if no selection bias is known. Examples of groups at significant excess risk of IHD are those self-employed in the textile industry, self-employed hairdressers, foremen in the construction industry, bakers, medical and industrial laboratory technicians, telephone assistants and unskilled tube and sheet workers in shipyards. PMID- 1634306 TI - Risk of mortality and coronary heart disease by marital status in middle-aged men in The Netherlands. AB - Between 1972 and 1974, a cardiovascular screening survey was conducted in a stratified sample of 3365 men aged 45-59 in Rotterdam, the Netherlands. Follow-up data collected in 1982 were used to examine the association between marital status and mortality and coronary heart disease while adjusting for various control variables. Nonmarried men had significantly higher relative risks (RR) (95% confidence interval (CI)) of 1.7 (95% CI: 1.2-2.3) and 2.2 (95% CI: 1.2-4.2) for all-cause mortality and coronary mortality than the married. Never married men showed the most consistent relationships with all-cause and coronary mortality, with RR of 2.3 (95% CI: 1.6-3.4) and 2.9 (95% CI: 1.4-6.2) respectively. The RR for these endpoints among the widowed and divorced were all close to unity, except for the risk of coronary mortality among the widowed, which was 2.9 (95% CI: 0.9-10.2). Not being married also increased the risk for fatal and total reinfarction, with RR of 3.6 (95% CI: 1.4-9.1) and 2.5 (95% CI: 1.1-5.6) respectively. The results suggest that in middle-aged Dutch males, the health consequences of not being married may differ for the never married, divorced, and widowed. Selective mating, differential lifestyles or health habits, and lack of social integration were offered as possible explanations. PMID- 1634307 TI - Intra-person variability of various physical activity assessments in the Kuopio Ischaemic Heart Disease Risk Factor Study. AB - We investigated the 12-month intra-person variability of various physical activity assessments used in the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) in 51 men aged 54 years. The methods were a 24-hour total activity recording, a 12-month leisure time activity history, a 7-day leisure time activity recall and a habitual occupational activity interview. More leisure time activity was reported in the retest. Intra-person variability was high for all physical activity indices. The proportion of the mean absolute test-retest difference out of the test-retest mean was 18% for the 24-hour total activity recording, 45% for the 12-month leisure time activity history, 86% for the 7-day leisure time activity recall, 70% for kilometres of conditioning activity per week (No. = 51) and 22% for the occupational activity interview (No. = 39). However, respective intraclass correlations for these indices were 0.43, 0.58, 0.35, 0.71 and 0.69. The physical activity assessments differ in observed intra person variability in accordance with the type of activity, time frame and the method of recall. Owing to its representative time frame and relatively small intra-person variability the 12-month history may be recommended for a standard instrument for population studies concerning leisure time activity. PMID- 1634308 TI - Corneal arcus and cardiovascular risk factors in Asians in Singapore. AB - This study was a cross-sectional random survey of the whole of Singapore, based on 2143 subjects (aged 18-69 years, response rate 60.3%). The presence of corneal arcus was determined by a doctor using the naked eye in good light. Cardiovascular risk factors were measured by standardized techniques. The prevalence rates overall of corneal arcus were: 18-29 years (males 0.5%, females 0.3%), 30-49 years (males 18.1%, females 13.3%) and 50-69 years (males 70.7%, females 55.3%). In the 30-49 age group, people with arcus had higher serum low density lipoprotein (LDL) cholesterol concentrations than people without arcus, the mean differences being, males 0.31 mmol/l (P = 0.040) and females 0.62 mmol/l (P less than 0.001) with an increased likelihood of having values greater than 5.5.mmol/l of males 1.8 (95% confidence interval (95% CI): 1.0-3.4) and females 2.6 (95% CI: 1.4-4.8). There were no significant differences for LDL-cholesterol in the 50-69 age group. Arcus was weakly associated with fasting plasma glucose in the 30-49 age group. Arcus was not associated with serum high density lipoprotein (HDL) cholesterol, serum fasting triglyceride, blood pressure and cigarette smoking. It is concluded that while corneal arcus is primarily an age related change, its formation is accelerated by high serum LDL-cholesterol so that in people under 50 years it is a marker for the condition. PMID- 1634309 TI - National standards of blood pressure for children and adolescents in Spain: international comparisons. The Spanish Group for the Study of Cardiovascular Risk Factors in Childhood and Youth. AB - This study determined age-specific patterns of blood pressure (BP) in Spanish children aged 1-18 years for the purpose of developing BP guidelines for this population. Age- and sex-specific BP levels were constructed by pooling data from 15 studies conducted in Spain. Pooled mean BP levels were then compared with those reported by the US Second Task Force on Blood Pressure Control in Children and those recently reported from a separate pooled analysis of the relevant published surveys collected worldwide. In the Spanish data, the average 1-year age increment in Systolic BP (SBP) was uniform for boys and girls until 13 years at 2 mmHg; for boys aged 13-18 the increase was 1.3 mmHg/year; in contrast, girls reached their maximum values at age 13 and the means remained basically unchanged for female adolescents. Fifth-phase diastolic BP (DBP5) values showed a uniform increase for both boys and girls from ages 6 to 18 years at 0.9 mmHg/year. In most age-sex subgroups, mean SBP values were higher (7-8 mmHg on average) in Spain than in the US. However, Spanish values for SBP were in general only slightly higher or approximately equal to those for the international data, from ages 6 to 18 years. The patterns of change in SBP with age differed somewhat in the three data sets. Comparisons for DBP were limited to the age groups for which readings of DBP5 were available. For DBP5, only slight differences between the Spanish and International pools were observed (ages 6-18 compared), but these values were notably higher than those from the US (ages 13-18 compared). These findings suggest that the use of any particular age-based standard to evaluate readings in children in diverse populations cannot be recommended, at least until there is a better understanding of the true differences in BP between populations. PMID- 1634310 TI - Discrimination of smoking status by thiocyanate and cotinine in serum, and carbon monoxide in expired air. AB - To develop a procedure for maximizing the discrimination of smoking status, the authors analysed parallel samples of thiocyanate and cotinine in serum, and carbon monoxide (CO) in expired air in a cohort of 145 male subjects aged 45-65 years. The sensitivity and specificity were 93% and 82%, 97% and 83%, and 98% and 100% for thiocyanate, cotinine, and CO respectively. The results were not significantly improved when combining two or three methods as compared with CO separately. Also, cotinine in urine was analysed in a subgroup of 21 subjects. The correlation coefficient between cotinine in serum and urine was 0.92. In a subgroup of 44 subjects with extensive information on smoking habits, CO was the only indicator significantly related to the quantity of tobacco smoked. We conclude that CO seems sufficient for validating smoking status, but as atypical smokers who are vulnerable to misclassification may be overrepresented in smoking cessation programmes, combining two methods could still be useful. Validating the amount of tobacco smoked is of limited use with the current methods. PMID- 1634311 TI - Past and present smoking behaviour and its association with health-related habits in selected Israeli working populations. The Cordis Study. AB - Comprehensive surveys on the characteristics of smokers provide important data for the targeting and monitoring of smoking cessation programmes, and making international comparisons. Current information on this subject in Israel is very limited. During 1985-1987, the prevalence and correlates of cigarette smoking were examined in 5281 employees in Israeli industry, screened in the framework of the CORDIS study. The prevalence of smoking in men ranged from 44.7% in the age group 20-24 years to 28.0% in those aged 55-64. For women the prevalence ranged from 23.2% to 15.0% over the same age range. Ethnic differences were most marked in younger males with the highest prevalence in those of North African origin. Among females, the highest prevalence was among those of Western European origin. In most age groups, the highest proportion of exsmokers was found among those of Eastern European origin, except for older females where differences were not significant. Among males, educational differences were strong, with those of lower education smoking the most, whereas among females no significant differences were observed. For both sexes, past smokers were more prevalent in the highest education category. There was a cohort effect in declining age at starting smoking in both sexes and females tended to start smoking about 2 years older than males. Exsmokers tended to have been heavier smokers than current smokers, suggesting that heavy smokers may be more likely to quit than light smokers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634312 TI - The European Community 'avoidable death indicators' in Sweden 1974-1985. AB - Avoidable mortality in Sweden 1974-1985 was analysed using a European Community (EC) Working Group list of 'avoidable death indicators." The list includes causes of death that in certain age groups were defined as indicators of the outcome of medical care intervention or for some conditions, indicators of the national health policies. About 10 out of 14 medical health care indicators occurred in less than 50 cases per year. Death rates decreased over the 12-year period studied for most avoidable death indicators. For women, however, the death rate for malignant neoplasms of the trachea, bronchus and lung increased significantly. Swedish total mortality for ages 5-64 years was lower than the EC standards 1974-1978 and 1980-1984. Most of the avoidable causes of death had a relatively low standard mortality rate (SMR) when compared to both the EC standard and to the Swedish SMR for total mortality. For asthma, however, the Swedish SMR was higher. The development and implementation of the avoidable death concept and methodology is discussed. PMID- 1634314 TI - Comparison of the incidence of insulin-dependent diabetes mellitus in childhood among five Baltic populations during 1983-1988. AB - We have carried out a comparison of the incidence of childhood onset insulin dependent diabetes mellitus (IDDM) between five populations around the Baltic Sea. These were Finland, Estonia, Latvia, Lithuania and Poland. The risk of IDDM is highest in the world in Finland and also very high in Sweden, on the western and northern side of the Baltic Sea. The risk of IDDM in children on the eastern side of the Baltic Sea has not been known before. The data collection period covered the years 1983-1988. A marked variation in incidence was seen within this relatively small geographical area. Among these five populations, the incidence increased with the latitude. Our present results confirmed the very high incidence of IDDM in Finland. The average age-standardized yearly incidence of IDDM/100,000 was in males under 15 years of age 36.9 in Finland, 10.7 in Estonia, 6.4 in Latvia, 6.5 in Lithuania and 6.0 in Poland. In females the incidence was 31.6, 10.0, 6.9, 7.0 and 6.4 in these five populations, respectively. The differential in incidence in Estonia as compared with Latvia, Lithuania and Poland was statistically significant (P = 0.0002). A slight male excess in incidence was found in countries with higher incidence--Finland and Estonia, but in lower incidence countries the sex ratio was opposite (P = 0.019 for the interaction sex-population). During 1983-1988 the incidence increased significantly in Finland but not in other populations although a large year-to year variation in incidence was observed in each country, particularly in males. We recorded a peak in IDDM incidence in most of these populations around 1986. PMID- 1634313 TI - Association of body build with non-insulin-dependent diabetes mellitus and hypertension among Chinese adults: a 4-year follow-up study. AB - Both cross-sectional and longitudinal studies on the association of body build with non-insulin-dependent diabetes mellitus (NIDDM) and hypertension were conducted in Taiwan during the period 1986-1990. The cross-sectional study, was carried out in 1986 in Ta-An District of Taipei City and five rural areas evenly distributed in Taiwan Province. A total of 11,478 randomly selected subjects aged 40 years or over were surveyed. World Health Organization designations of diabetes and hypertension were followed. The longitudinal observation was made in 1990 for the cohort living in Taipei City who had neither diabetes nor hypertension in 1986. Of 2822 subjects, 1873 individuals participated in the follow-up study and 52 had died, giving a response rate of 67.6%. In comparison with Caucasian or Polynesian populations, Chinese adults have a much lower prevalence of obesity (body mass index [BMI] greater than 30 kg/m2). Univariate and multivariate analyses revealed both diabetes and hypertension increased as body build became heavier. The age-adjusted prevalence ratio and relative risk for the fourth quartile of BMI compared to the first quartile were 2.72 and 2.87, respectively, for diabetes as well as 2.96 and 2.24, respectively, for hypertension. Multiple logistic regression analyses revealed a slightly higher increase in prevalence of hypertension than that of diabetes for every 1 kg/m2 increase in BMI (1.16-fold and 1.12-fold, respectively), while a similar increase in BMI resulted in a slightly higher relative risk of diabetes than that of hypertension (1.14-fold and 1.11-fold, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634315 TI - Relationship between the degree of individual space-time clustering and age at onset of disease among multiple sclerosis patients. AB - A previous study of 381 multiple sclerosis (MS) patients from Norway has shown significant clustering of residence in adolescence among contemporaneous patients. Using a regression model with individual degree of clustering determined by Monte Carlo methods, this study utilizes the same data and shows a significant correlation (P = 0.002) between the degree of clustering and age at clinical onset of disease. A high degree of clustering in adolescence indicated a low age at clinical onset. This association was also verified independently of the regression model. The finding supports the theory of a common viral agent acting epidemically among nonpre-exposed individuals during adolescence, with MS developing in individuals with other necessary factors, such as a genetic predisposition. PMID- 1634316 TI - Estimating the incidence of dementia in the community from prevalence and mortality results. AB - This paper reports a series of computer simulations of the incidence of dementia, and its relationship to age. The simulations use known prevalence and mortality data from a single source: Liverpool. Comparison is also made with additional UK, European, and international figures to add stability to the estimates. The paper concludes that with our present knowledge we can either model prevalence or incidence, but not both, and suggests that more information is especially needed for the older groups. PMID- 1634317 TI - Correlated nondifferential misclassifications of disease and exposure: application to a cross-sectional study of the relation between handedness and immune disorders. AB - In cross-sectional studies, misclassifications of exposure and of health status may be related. For instance some subjects may tend to overreport both exposure and disease. A misclassification is said to be nondifferential if the sensitivity and the specificity which characterize it do not depend on the true status of the subjects for the other variables. Nondifferential misclassifications of two dichotomic variables may be correlated if the probability of being misclassified for one of them depends on the presence of an error of classification for the second one. Models are presented to estimate the bias induced by correlated nondifferential misclassifications on an odds ratio whose true value is unity. For most usual situations, when the great majority of the subjects are healthy and nonexposed, the influence of overreporting is shown to be larger than that of underreporting. It appears to be relatively easy to find a spurious, but significant, relationship. Real data are analysed to show that the potential consequences of correlated nondifferential misclassifications are not purely theoretical. In a sample of 1676 subjects from the general population we observed significant relations between left-hand shift and various aspects of health status: reporting a history of eczema, experience of a serious health problem in the past, experience of a serious health problem presently, use during the last month of analgesics or of drugs for circulatory problems, or digestion, consultation with a physiotherapist or hospitalization during the last year. These results, as with many similar ones previously reported, are highly suggestive of an information bias. They are less easily explained by biological hypotheses, e.g. Geschwind's theory of cerebral lateralization, than by correlated misclassifications resulting from overreporting of both the use of the left hand and the existence of some health problems by healthy right-handers. The modelling used in this report supports this hypothesis. PMID- 1634318 TI - Seasonality in tropical AIDS: a geographical analysis. AB - This paper presents evidence that the growth rate of the AIDS epidemic at the district level in Uganda, Central Africa, displays a seasonally recurring geographical pattern, with epidemic acceleration in some areas of the country in the first 8 months of each year. The spatial and temporal variations in acceleration appear to be correlated with the predominant agricultural systems in different parts of Uganda. Based upon the frequently hypothesized relationship between malnourishment and the progression to clinical AIDS in HIV-infected people, it is suggested that the variations in epidemic speed reflect the seasonal patterns of nutritional deficiency which occur under some tropical agricultural systems. These preliminary findings require further verification since they have important implications for directing nutrition-related remedial responses to the AIDS epidemic in tropical countries where malnutrition and endemic HIV infection coincide. PMID- 1634319 TI - Assessment of epidemiological and HIV/AIDS publications in Africa. AB - To assess the quantity of epidemiological publications emanating from Africa, three international epidemiology journals were examined. In addition, a separate MEDLINE search was undertaken for 1987 and 1989-1990 to assess AIDS/HIV prevalence and incidence publications. Of 361 general epidemiological articles examined for 1974-1975, 49.3% were from the US, 20.5% from the UK, 11.1% from Europe, 10.2% from the rest of America, 4.4% from Asia, 3.9% from Australasia and 0.06% (only two) from Africa. The overall proportion from the USA declined to 44.0% by 1989-1990; from the UK to 11.1% while from South America and Australasia the proportion remained similar. Striking increases occurred in Europe and to a lesser extent in Asia. By 1989-1990 African articles contributed 3.6% (31) of the total. While over 90% of first authors came from the study region in the US, UK, Europe and Australasia; 85.7% in Asia; 70.8% in South America in 1989-1990, in Africa only 32.2% were authors from their continent. Of the 220 published articles on AIDS/HIV epidemiology 6.8% emanated from Africa in 1987 and 12% of 606 articles in 1989-1990. African scientists were first authors in 46.7% of articles from the continent in 1987 and only 35.5% in 1989 and 1990. In 1987, 60% of the articles were co-authored by overseas scientists of various nationalities while collaborative publications increased to 78.4% in 1989-1990. Only 15% of these articles were published in African Journals. This study stresses the urgent need for improving all aspects of epidemiological research and training in Africa with particular need with respect to AIDS/HIV research capacity. PMID- 1634320 TI - Human immunodeficiency virus infection among intravenous drug addicts in Israel- stable low prevalence over 34 months. AB - A serological survey of 300 Israeli intravenous drug addicts in 1988-1989, showed a 2.3% prevalence of antibodies to human immunodeficiency virus (HIV), very similar to the finding of a previous study (2%) performed in the same population in 1986. Travel and drug injection abroad continue to be the most significant predictors of HIV seropositivity in this group. The relatively uncommon use of cocaine and the absence of 'shooting galleries' in Israel, appears to explain best the stable low prevalence of HIV infection among parenteral drug addicts in this country. PMID- 1634321 TI - Various factors associated with the manifestation of influenza-like illness. AB - A survey enrolling 814 schoolchildren was conducted immediately after a peak epidemic in the 1988-1989 influenza season and then a case-control study for influenza-like illness (ILI) was carried out using information concerning illness onset and usual lifestyle. Based on the analysis of the correlations among symptoms and actions taken due to symptoms, cases were defined as those with fever greater than or equal to 38 degrees C and subsequent absenteeism and medical consultation during peak epidemic; within this, mild-ILI (MILI) was defined as fever greater than or equal to 38 degrees C and less than 39 degrees C, and severe-ILI (SILI) as fever greater than or equal to 39 degrees C. Controls were defined as those with no symptoms (NS) during that period. Adjusted odds ratios (OR) were obtained through an unconditional logistic regression model between the MILI (80) or SILI (48) and NS (196) groups from among respondents (803). For MILI, increased risks were observed for easily-inflamed tonsils (OR = 3.0, 95% CI: 1.7-5.4); and larger family size (1.9, 1.1-3.4); with decreased risks for higher school grades (0.4, 0.2-0.9); frequent intake of vegetables or fruits other than green/yellow vegetables (0.5, 0.3-1.0); and larger room space per capita (0.4, 0.2-0.9). For SILI, there were increased risks for easily inflamed tonsils (3.8, 1.8-8.1) and history of doctor-diagnosed asthma (2.9, 1.2 6.7); and decreased risks for higher grades (0.2, 0.1-0.6), frequent intake of milk or dairy products (0.3, 0.1-0.6) and vaccination (0.3, 0.1-0.8). PMID- 1634322 TI - Subacute sclerosing panencephalitis in The Netherlands--1976-1990. AB - Since 1976, when general immunization against measles was introduced in the Netherlands, all new cases of subacute sclerosing panencephalitis (SSPE) were registered and detailed data about immunization, epidemiology and disease progression were collected on them. Up to 1991, 99 new patients have been registered of which 81 were born in this country and 18 elsewhere. From 1981 onwards, the incidence of SSPE among those born in the Netherlands decreased gradually from 13 cases per year to one case per year. This decrease is attributed to the large scale of immunization against measles. Three SSPE patients had been immunized against measles, all of them without a history of clinical measles. Epidemiology and risk factors of SSPE did not differ from those reported in other countries. An exceptional cluster of four patients in one town, who had measles in the same year, is reported. Progression of SSPE appeared to be age related. A total of 28 patients was treated with Inosiplex; no significant effect on survival in stage 3 of the disease was found. PMID- 1634323 TI - Choosing an appropriate measure of diarrhoea occurrence: examples from a community-based study in rural Kenya. AB - Epidemiological studies which aim to identify protective or risk factors for diarrhoea may rely on any of several established measures of disease occurrence, including cumulative incidence, (CI), incidence density (ID), and point prevalence (P); each with its own strengths and limitations. Comparison of these measures was afforded by a community-based study in rural Kenya in which the incidence and prevalence of diarrhoea were measured simultaneously but by independent means in the same group of children. In a cohort study, CI and ID among 138 infants (aged 0-6 months) were 26.1% and 1.41 episodes per 100 infant weeks, respectively. Among 111 toddlers (aged 18-29 months) CI and ID were 39.6% and 1.96 episodes per 100 toddler-weeks, respectively. In a cross-sectional study of these children, the Ps among infants and toddlers were 9.8 and 6.1%, respectively. Data on incident cases required more time and resources to obtain and evidenced more underreporting of diarrhoea episodes relative to the prevalence data. Other community-based studies have reported the ID of diarrhoea five times more often than any other measure, but appear to have calculated ID incorrectly. The infrequency with which CI and P are reported does not reflect their actual utility. PMID- 1634325 TI - Estimating prevalence of injecting drug use in an urban population: limitations of the three-sample estimation procedure. PMID- 1634324 TI - Seroepidemiological characterization of a syphilis epidemic in the Republic of the Marshall Islands, formerly a yaws endemic area. AB - The annual numbers of reported cases of syphilis in the Republic of the Marshall Islands (RMI) increased from none in 1983 to more than 600 in 1989, suggesting a large outbreak of syphilis. Much of the increase resulted from expanded serological screening. The apparent outbreak of syphilis, therefore, may have been partly the result of increased surveillance or, since the RMI was formerly a yaws endemic area, possibly due to a resurgence of yaws. To address this problem and better characterize the epidemic, we analysed results from a 1989/90 Ministry of Health Services mass serological screening on Majuro Atoll, the main population centre. Serum specimens from 9160 people (86% of residents aged 15-44 years) on Majuro were screened with the rapid plasma reagin (RPR) card test; we repeated the RPR and performed a confirmatory microhaemagglutination assay for Treponema pallidum-specific antibodies (MHA-TP) on a sample of serum specimens. To estimate the seroprevalence of syphilis, we also tested a sample of RPR nonreactive specimens by MHA-TP. Among people less than 45 years of age, total (11.5%) and high-titre (5.2%) seropositivity rates were highest in the 20-24 year age group, as was MHA-TP seroprevalence (15.9%). These results suggested that a large outbreak of syphilis was responsible for the observed seroreactivity. Cumulative incidence modelling and comparisons with the results of a previous serosurvey conducted in 1985 suggested that the duration of the syphilis epidemic was approximately 10 years and that incidence had not increased appreciably since 1985. PMID- 1634326 TI - Glycoconjugates of opioid peptides. Synthesis and biological activity of [Leu5]enkephalin related glycoconjugates with amide type of linkage. AB - Three N-glycoconjugates of the general formula H-Tyr-Gly-Gly-Phe-Leu-NH-R (R = carbohydrate residue) were synthesized in order to determine the influence of some carbohydrate molecules (6-amino-6-deoxy-D-glucopyranose, 2-amino-2-deoxy-D glucopyranose, beta-D-glucopyranosylamine) on the biological activity, conformation, and stability of the opioid pentapeptide [Leu5]enkephalin. For the preparation of this compound different methods of peptide synthesis (active ester and mixed anhydride) were investigated. In comparison with [Leu5]enkephalin, all three N-glycoconjugates showed higher potency in the guinea pig ileum assay and lower potency in the mouse vas deferens assay, indicating a decrease in delta opioid receptor selectivity. PMID- 1634327 TI - Ionization of tyrosine residues in human serum albumin and in its complexes with bilirubin and laurate. AB - Spectrophotometric titration of human serum albumin indicates that ionization of the 18 tyrosine residues takes place between pH 9 and 12.7. A Hill plot indicates that protons dissociate co-operatively from tyrosine residues, in pure albumin between pH 11.0 and 11.4 with a Hill coefficient 1.7, and in the bilirubin albumin complex between pH 11.2 and 11.7 with a Hill coefficient 1.6. With a stopped-flow technique it is shown that about seven of the tyrosines ionize fast, with rate constants well above 10(2) s-1, when pH is suddenly changed from near neutral to pH 11.76. Further residues ionize slowly, with rate constants around 10(2) s-1 or less. The N-form of albumin (pH 6) contains one more fast ionizing tyrosine than the B-form of albumin (pH 10). Binding of bilirubin or laurate to the albumin molecule (molar ratio 1:1) transforms one to three of the fast ionizing tyrosines to slowly ionizing. PMID- 1634328 TI - Complete structure of eclosion hormone of Manduca sexta. Assignment of disulfide bond location. AB - The locations of the three disulfide bonds of eclosion hormone (EH) isolated from Manduca sexta were assigned by sequence analysis of thermolysin fragments and by comparison of a key heterodimeric fragment to regiospecifically synthesized parallel and antiparallel isomers. We elucidated the complete structure of Manduca EH as a 62-residue peptide which has three disulfide bonds between Cys14 Cys38, Cys18-Cys34, and Cys21-Cys49. PMID- 1634329 TI - Cyclic hexapeptides derived from the human thymopoietin III. AB - Six diastereoisomeric cyclic hexapeptides of the partial sequence 39-44 of human thymopoietin III in which each residue was replaced with the D-amino acid were synthesized. In contrast to expectations, the yields from cyclization were not influenced by the location of the D-residue. PMID- 1634330 TI - Side reactions in solid phase synthesis of histidine-containing peptides. Characterization of two major impurities by sample displacement chromatography and FAB-MS. AB - The flow-polyamide synthesis of a histidine-containing sequence (Ac-YDNVLDHLTGR) produced two major impurities which were isolated through Sample Displacement Chromatography and characterized by Fast Atom Bombardment-mass analysis. The impurities correspond to the sequence Ac-YDNVLDH, and to a peptide with the Asp residue cyclized to a succinimide. The latter side-reaction took place during the acetylation procedure, and demands attention where capping procedures are planned in the synthesis of Asp-His sequences. PMID- 1634331 TI - NMR and molecular modeling characterization of RGD containing peptides. AB - The tripeptide sequence arginine-glycine-aspartic acid (RGD) has been shown to be the key recognition segment in numerous cell adhesion proteins. The solution conformation and dynamics in DMSO-d6 of the cyclic pentapeptides, [formula: see text], a potent fibrinogen receptor antagonist, and [formula: see text], a weak fibrinogen receptor antagonist, have been characterized by nuclear magnetic resonance (NMR) spectroscopy and molecular modeling. 1H-1H distance constraints derived from two-dimensional NOE spectroscopy and torsional angle constraints obtained from 3JNH-H alpha coupling constants, combined with computer-assisted modeling using conformational searching algorithms and energy minimization have allowed several low energy conformations of the peptides to be determined. Low temperature studies in combination with molecular dynamics simulations suggest that each peptide does not exist in a single, well-defined conformation, but as an equilibrating mixture of conformers in fast exchange on the NMR timescale. The experimental results can be fit by considering pairs of low energy conformers. Despite this inherent flexibility, distinct conformational preferences were found which may be related to the biological activity of the peptides. PMID- 1634332 TI - High level synthesis of biologically active recombinant trichosanthin in Escherichia coli. AB - Two forms of recombinant trichosanthin (rTCS) were synthesized in high levels in Escherichia coli by putting the TCS cDNA under the control of a T7 RNA polymerase directed promoter. Purification schemes were developed to isolate the recombinant protein from both soluble and insoluble fractions. Form I rTCS possessed the mature TCS sequence and had similar biological activities as the natural protein. Its IC50 was approximately 0.13 nM in an in vitro rabbit reticulocyte translational system and a dose of around 35 micrograms protein per 25 g body weight was sufficient to induce complete abortion in mice. Form II rTCS had a propeptide of 19 aa at the C-terminus and was five times less active than Form I in inhibiting protein synthesis by a rabbit reticulocyte lysate. PMID- 1634333 TI - The antineoplastic effect of vitamin D in transgenic mice with retinoblastoma. AB - Vitamin D has been shown to inhibit growth of human retinoblastoma in tissue culture and nude mouse heterografts. We have described a heritable transgenic mouse model of retinoblastoma. The in vivo efficacy of 1,25 dihydroxycholecalciferol (vitamin D3) was examined by administering this agent to transgenic mice with retinoblastoma. Forty-six 8-10-week-old transgene-bearing mice were injected intraperitoneally for 5 wk. Experimental animals received 0.05 microgram (15 animals) or 0.025 microgram (15 animals) of vitamin D. Sixteen control animals received only a mineral oil vehicle. Eyes were enucleated at 5 mo and were examined histologically by two investigators in a masked fashion. All control animals demonstrated bilateral involvement of retinoblastoma. Four eyes in the low-dose group and six eyes in the high-dose group had no evidence of retinoblastoma. Eyes treated with vitamin D3 showed less extensive involvement of the retina by retinoblastoma. Vitamin D-treated animals demonstrated tumors confined to the retina, whereas control animals demonstrated larger tumors, more often invading the vitreous, anterior chamber, and choroid. Thus, Vitamin D inhibited the growth and local extension in a dose-dependent fashion. PMID- 1634334 TI - Microsurgery of the retina with a needle-guided 193-nm excimer laser. AB - This article presents a method used to guide the beam from an argon fluoride excimer laser to make it suitable for microsurgical purposes and confine it to areas that can be varied in dimension from 1 micron to tens or hundreds of microns. This approach guides the excimer laser beam with an articulated mechanical arm and confines it with variable-diameter tapered tubes, possibly allowing the use of this laser in in vitro retinal surgery with endolaser techniques. Currently, because of the lack of a delivery and focusing system for the 193-nm argon fluoride beam and its absorption by biologic liquids, this laser is used exclusively in ophthalmology for topical applications, such as corneal sculpting. This new method resolves these problems in a unique way with impressive results. Specifically, it was shown that, with this needle-guided excimer laser, it is possible to remove retinal tissue accurately without detectable damage to surrounding cells. Applications of this new technique in retinal surgery are discussed. PMID- 1634335 TI - Effect of body temperature on threshold for retinal light damage. AB - Body temperature is known to influence the threshold for retinal light damage, but the magnitude of the effect has varied substantially between previous studies. The purpose of the present study was to establish a quantitative relation between body temperature in the range of 30-42 degrees C and dose of radiation for a just visible change in fundo. Anesthetized pigmented rats were exposed to 380 nm radiation for 10 min. Four intensities were simultaneously presented. Funduscopic changes were noted 2-3 d after exposure. At 30 degrees C, threshold dose was 6 J/cm2; at 42 degrees C, it was about 1 J/cm2. A fair fit to the data could be obtained with a linear regression between log threshold dose and temperature. The slope was -0.067. In an additional experiment, threshold dose at 500 nm and 41 degrees C body temperature was established at 400 J/cm2. These results agree with data in monkey and rabbit, but they vary from earlier data in rats that show a slope of -0.8. Exposure time, damage criterion, and the chromophores involved in retinal light damage are possible factors in the discrepancy. PMID- 1634336 TI - Sulfated proteoglycans in the human lamina cribrosa. AB - The sulfated proteoglycans in the normal human lamina cribrosa were studied by electron microscopy after cuprolinic blue dye binding. Within the cores of the laminar plates, three types of cuprolinic blue-positive proteoglycan filaments with different sizes were associated with collagen fibers. These filaments, which were partially sensitive to chondroitinase AC and chondroitinase B, were completely removed by chondroitinase ABC and were identified as chondroitin/dermatan sulfate proteoglycans. In addition, small punctate and filamentous structures that stained with cuprolinic blue were associated with the basal laminae of astrocytes and blood vessels. Enzyme chondroitinase ABC had no effect, but heparinase digested all of these basement membrane-associated structures, indicating that they represented heparan sulfate proteoglycan molecules. Keratanase did not affect any of the cuprolinic blue-positive materials. This investigation illustrates the ultrastructural distribution and morphology of proteoglycans in the human lamina cribrosa and provides baseline information for future studies regarding the roles of proteoglycan molecules in diseases such as glaucoma. PMID- 1634337 TI - Autoregulation of choroidal blood flow in the rabbit. AB - Previous studies show that choroidal blood flow is not autoregulated when intraocular pressure (IOP) is increased to raise venous pressure and lower the perfusion pressure gradient. However, the autoregulatory response to changes in mean arterial pressure (MAP) is unclear. In the current study, the perfusion pressure gradient (MAP-IOP) was altered by (1) decreasing MAP while IOP was held at 5, 15, and 25 mmHg, and (2) increasing the IOP at the prevailing MAP in anesthetized rabbits (n = 8). An occluder on the thoracic vena cava was used to vary MAP; this was monitored through an ear artery catheter. Two catheters were inserted in the vitreous to monitor and control IOP. Choroidal blood flow was measured by laser Doppler flowmetry using a slender stainless-steel probe positioned next to the retinal surface. The efficacy of autoregulation depended on the IOP. When IOP was held constant at 5 mmHg, choroidal blood flow did not fall until the perfusion pressure gradient was less than 40 mmHg. The pressure flow relationship became progressively more linear (ie, the efficacy of autoregulation decreased) when the IOP was held constant at 15 and 25 mmHg. When IOP was varied and MAP was held constant, the pressure-flow relationship was linear at IOPs greater than 20-25 mmHg. However, choroidal blood flow was pressure independent when the IOP was less than 20-25 mmHg. Simultations using a myogenic mathematic model of the choroid gave results similar to the experimental observations. It was concluded that a myogenic mechanism may be responsible for the autoregulation of choroidal blood flow in the rabbit. PMID- 1634338 TI - Motion thresholds in retinitis pigmentosa. AB - Minimum displacement thresholds, or dmin, were measured in 29 subjects with retinitis pigmentosa (RP) and 10 subjects with normal vision. The results showed that RP can affect an observer's ability to judge the correct direction of motion in a random-dot pattern. The majority of RP subjects had elevated dmin. They required a larger displacement to perceive the correct direction of motion. Only 5 of the 29 RP subjects had thresholds within two standard deviations of the mean of the normal-observer distribution. Moreover, three RP subjects were unable to detect the correct direction of motion regardless of the displacement magnitude, and four RP subjects consistently reported motion in the opposite direction at small displacements. The results cannot be explained by abnormal temporal processing or a reduction in the effective luminance. There was a statistically significant correlation (r = 0.72, P less than 0.001) between log threshold and log MAR, consistent with the hypothesis that a reduction in the spatial density of the photoreceptors contributes to the motion-threshold elevation. Motion thresholds also were measured in subjects with normal vision under conditions of simulated "photoreceptor" dropout. The results showed that a random elimination of information from over 25% of the image positions significantly elevates motion thresholds. These results also support the spatial-density reduction hypothesis. PMID- 1634339 TI - The neurophysiologic significance of frontal negativity in pattern-reversal visual-evoked potentials. AB - To demonstrate that the frontal negative potential (N100) does exist in response to pattern-reversal visual stimulation and its independence of the dipole source from the major occipital positive potential (P100), modifications of P100 and N100 with changes in the check size, contrast, and luminance of the stimulus pattern were studied in healthy subjects. Eight different check sizes (10-90 min of arc), eight different contrast levels (10-85%), and six different luminance levels (11-180 cd/m2) were used. Changing the stimulus conditions modified the latencies and amplitudes of P100 and N100 in different ways. P100 latency had a band pass spatial tuning function against check size; N100 latency did not. P100 was sensitive to changes in contrast and luminance; N100 was less dependent on these parameters. These findings suggest the existence of different physiologic properties for N100. Consequently, frontal negativity is considered to be independent of P100. PMID- 1634340 TI - Collagen gel contraction by cells associated with proliferative vitreoretinopathy. AB - The capacities of porcine choroidal fibroblasts, retinal glial cells, and retinal pigment epithelial cells to contract collagen gels in vitro were compared. Experiments with varied cell numbers indicated that glial cells are the most effective, followed by choroidal fibroblasts and retinal pigment epithelial cells. Analysis of the secretory products from cultures of these cell types revealed that retinal pigment epithelial cells synthesize and secrete peptides that promote fibroblast contraction of collagen gels in vitro. The mechanism of action of the retinal pigment epithelial cell-secreted contraction promoter was compared with that found in serum (type A) and secreted by cultured endothelial cells (type B). Like the serum factor, the retinal pigment epithelial cell secreted factor was not dependent on active protein synthesis by the target cell and must be present continuously to promote contraction. PMID- 1634341 TI - Quantitative assessment of growth stimulating activity of the vitreous during PVR. AB - This report postulates that the activity of cellular proliferation along the surface of the retina during proliferative vitreoretinopathy (PVR) is reflected in the aggregate effect of proliferation-inducing growth factors in the vitreous. A method for quantifying the "net" proliferation-inducing capacity of an individual vitreous sample was developed and this assay was used to evaluate the vitreous proliferative activity in a model for experimental PVR. Vitreous was aspirated sequentially after onset of fibroblast-induced PVR in a rabbit model. A simple bioassay for the "aggregate" stimulating activity was developed and each sample was assigned a quantitative value in terms of "proliferation units" (PU). Experimental eyes demonstrated a wide range of stimulating activity (0-1765 PU), but control eyes showed uniformly low levels of activity (0-337 PU). Experimental eyes that ultimately developed retinal detachment displayed higher levels of proliferative activity than did those eyes destined to remain attached. The differences were statistically different by day 3, prior to the onset of clinical retinal changes. We conclude that quantification of vitreous proliferation stimulating activity is possible and that this method might be useful for screening eyes at high risk for the development of recurrent retinal detachment from PVR. PMID- 1634342 TI - Isolation and cultivation of human iris pigment epithelium. AB - There have been very few attempts to isolate and culture human iris pigment epithelium (IPE). Earlier efforts that used whole iris explant methods did not achieve pure cultures of IPE. We have developed methods for separating the IPE from the iris stroma of post-mortem eyes that avoid contamination by other cell types. Three different isolation methods were studied: direct dissection, enzyme digestion, and enzyme-assisted microdissection. The latter method yielded the best results. After treatment with enzyme solution, the IPE was easily separated from the stroma under the stereomicroscope and subsequently cultured with supplemented F12 medium. With this method, approximately 2.3 x 10(5) cells were isolated from each iris with an average viability of 90.2%. IPE cells isolated from 19 of 24 eyes grew to confluence in primary culture. The IPE could be maintained in pure culture for many generations over several months with up to 20 population doublings. Cultured IPE demonstrated cytokeratin and S-100 protein by immunocytochemistry. Some of these cells also displayed desmin, indicating origin from the anterior IPE. Cultured IPE cells retained most of the characteristics of IPE in vivo, such as apical/basal polarization, microvilli, and many cell junctions. Gradual dilution of pigment occurred in the dividing IPE cells, suggesting an inability to produce melanin in vitro. A subpopulation of the IPE cells contained myofilaments by electron microscopy, also indicating a anterior IPE origin. This method provides a source for large numbers of human IPE cells and could be useful in studies of the biology of IPE and the role of IPE in pathogenesis of several eye diseases, most notably exfoliation syndrome and its associated glaucomas. PMID- 1634343 TI - Corneal function after storage in dexsol or optisol. AB - Rabbit corneas were stored in Dexsol or Optisol (Chiron, Irvine, CA) for up to 2 wk at 4 degrees C. The thickness of corneas placed in Dexsol decreased 10 microns after they were placed initially in Dexsol, then increased approximately 8 microns/d for 7 d and 3 microns/d thereafter. Corneas placed in Optisol decreased 35 microns in thickness initially, then increased 2 microns/d thereafter. Human corneas showed similar thickness changes to those of the rabbit when stored in these media. After 5.5, 10, and 14 d in storage, rabbit corneas from each medium were cultured to assess their net deturgescence ability. Identical groups were cultured in media containing 20 microM ouabain to monitor the corneas' passive swelling characteristics. Corneas stored in either medium showed similar net deturgescence and passive swelling patterns after each storage period. Deturgescence rates decreased with increasing storage time, primarily because the rates of passive corneal swelling increased with storage time. Knowledge of the net deturgescence and passive swelling rates allowed an estimation of the total deturgescence activity of corneas after removal from Dexsol or Optisol. The total deturgescence activity of corneas stored in Dexsol for 5.5, 10, and 14 d was 85%, 68%, and 63% of control corneas, which were processed identically but not stored before culture. Corneas stored in Optisol exhibited 87%, 71%, and 69% of control deturgescence activity, respectively. These experiments show that Optisol was not significantly better than Dexsol in retaining poststorage corneal deturgescence activity but was superior to Dexsol in preventing corneal swelling during storage. PMID- 1634344 TI - Myopia and refractive error in dogs. AB - The refractive error of 240 phakic dogs of various breeds was measured using streak retinoscopy and averaged (-0.27 +/- 1.41 D relative to infinity). Analysis by breed showed that the German Shepherd, Rottweiler, and Miniature Schnauzer breeds had an increased prevalence of myopia with an average refractive error of 0.86 +/- 1.31 D, -1.77 +/- 1.84 D, and -0.66 +/- 1.05 D, respectively. Myopia also was found in older dogs with marked nuclear sclerosis of the crystalline lens. Fifty-three percent of all German Shepherd dogs in a veterinary clinic population (n = 58 eyes) had a myopic refraction of greater than or equal to 0.50 D; 64% of all Rottweiler dogs (n = 28 eyes) were myopic. An in-depth investigation of German Shepherd dogs, using A-scan ultrasonography, photokeratoscopy, and streak retinoscopy, was done at Guide Dogs for the Blind (San Rafael, CA). By contrast with the results obtained in the veterinary clinic population, the overall average refractive error of guide dog German Shepherd dogs (n = 106 eyes) was +0.19 +/- 0.81 D, and only 15% of these dogs were myopic. The axial length and corneal curvature of myopic eyes did not differ significantly from nonmyopic eyes. PMID- 1634345 TI - Calpain in rat cornea. AB - This study was conducted to provide a description of calpain proteolytic enzyme (EC 3.4.22.17) in normal rat cornea and to document immunohistochemical changes in calpain distribution during maturation. Corneal soluble proteins were fractionated by diethylaminoethyl chromatography on high-performance liquid chromatography. Fractions were analyzed for calpain by enzyme-linked immunosorbent assay, immunoblotting, and caseinolytic enzyme activity with fluorescein isothiocyanate-labeled casein. Calpain II from the soluble fraction of 2-week-old and 3-month-old rat corneas eluted at a similar NaCl concentration (220-240 mmol/l) as calpain II from other tissues, was inhibited by E64, contained an 80-kilodalton subunit in immunoblots, and was present at specific activity of 473 units per gram of protein in 3-month-old rats and 801 units per gram of protein in 2-week-old rats. Calpain antigen also was present in the ethylenediaminetetraacetic acid and EGTA washed insoluble fraction of cornea. Calpain was found (by immunohistochemical analysis) in all layers of the epithelium but not in the stroma. Enzyme-linked immunsorbent assay, immunoblots, and immunohistochemical analysis showed that calpain in the whole cornea did not change with corneal maturation. It was hypothesized that calpain in the cornea may be involved in the turnover of epithelial cells during normal maturation. PMID- 1634346 TI - Defective processing of motion-defined form in the fellow eye of patients with unilateral amblyopia. AB - The following three measurements were made on a group of 20 pediatric and 5 adult patients with unilateral amblyopia: (1) speed threshold for recognizing motion defined dotted letters; (2) recognition acuity for isolated solid letters of 4% contrast; and (3) Snellen line acuity for high-contrast letters. Normal limits were established with a group of 30 pediatric and 10 adult control subjects. The main finding was that, in amblyopic children, a high percentage (83%, 15 of 18) of fellow eyes showed a degraded ability to recognize motion-defined letters, even though Snellen acuity and 4% letter acuity were normal for age. The fellow eyes of all nine patients with strabismic amblyopia showed this pattern of loss, as did four of six fellow eyes of patients with anisometropic amblyopia and two of three fellow eyes of patients with anisometropic plus strabismic amblyopia. Only two clinically unaffected eyes were normal for motion-defined letters. These eyes belonged to patients with anisometropic amblyopia. Eighteen of the 19 previously amblyopic eyes tested were abnormal for motion-defined letters even though Snellen acuity was within normal limits for 6 of these eyes. In adults, only one of five fellow eyes failed the motion-defined letter test. It was concluded that the degradation of form perception associated with amblyopia can be different for luminance-defined and motion-defined form and that defective processing of motion-defined form is common in the fellow eyes of children with unilateral amblyopia. PMID- 1634347 TI - Two-dimensional optokinetic nystagmus induced by moving plaids and texture boundaries. Evidence for multiple visual pathways. AB - Horizontal and vertical components of optokinetic nystagmus (OKN) were measured using the magnetic search coil technique in normal human adults during presentation of simple and complex moving patterns. Simple patterns were gratings moving horizontally and obliquely. Complex moving patterns consisted of plaids formed by superimposed oblique motion of two sets of gratings or of illusory contours formed by offset discontinuities in gratings. Slow-phase OKN gains (eye velocity divided by stimulus velocity) induced by high-contrast type I and type II plaids were comparable with those generated by one-dimensional moving gratings. The axis of OKN for high-contrast plaids was along the resultant direction determined by the intersection-of-constraints rule and not along any component. With low-contrast presentations, OKN induced by type I patterns remained in the resultant direction, but the OKN direction induced by type II patterns was biased toward the components' directions. The OKN generated by texture boundaries embedded in real pattern motion was measured for motion of illusory contours having systematically varying directions. The gain of OKN induced by real motion was independent of the direction of illusory contour motion, but the gain to illusory contour motion decreased with increasing contour angles. All these results suggest that input signals for driving the optokinetic system come from visual areas extracting higher order two-dimensional motion information. PMID- 1634348 TI - The primary position of the eyes, the resetting saccade, and the transverse visual head plane. Head movements around the cervical joints. AB - Photographic and video analyses show that the primary position of the eyes is a natural constant position in alert normal humans, and the eyes are automatically saccadically reset to this position from any displacement of the visual line. The primary position is not dependent on fixation, the fusion reflex, gravity, or the head position. The primary position is defined anatomically by head and eye planes and lines that are localized by photography, magnetic resonance imaging, and x-rays of the head and neck. The eyes are in the primary position when the principal (horizontal) retinal plane is coplanar with the transverse visual head (brain) plane (TVHP), and the equatorial plane of the eye is coplanar with a fixed orbital plane (Listing's plane). Evidence is presented to indicate an active neurologic basis for the primary position instead of passive mechanical forces. A different understanding of the primary position and the conception of the TVHP may be valuable in analyzing oculomotor defects. PMID- 1634349 TI - Induction of elongation in cultured rat lens epithelial cells by FGF and inhibition by selenite. AB - The purposes of this experiment were to: (1) test if fibroblast growth factor (FGF) induced elongation of cultured rat lens epithelial cells (LEC) and (2) determine if selenite affected elongation of LEC. FGF (125-500 ng/ml) reduced the number of colonies of LEC, but it did not induce elongation when cells were cultured on plastic dishes. One hundred micromolar and, to a lesser extent, 10 mumol/l selenite also reduced the number of colonies of LEC. Coculture of FGF and selenite on plastic caused a synergistic reduction in the number of colonies. FGF (125-1000 ng/ml) induced a dramatic morphologic change in LEC. Elongated processes radiated from stellate-like cell aggregates when cells were cultured on reconstituted basement membrane matrix (Matrigel). Again, 100 mumol/l selenite and, to a lesser extent, 10 mumol/l selenite reduced the number of cell aggregates with processes on Matrigel. These results indicated that an inhibitory effect of selenite on the elongation of LEC may be a factor in the development of selenite cortical cataract. PMID- 1634350 TI - Decreased photoreceptor count in human eyes with secondary angle-closure glaucoma. AB - Glaucoma has been known to be associated with a loss of retinal ganglion cells and their axons throughout the fundus and a decreased count of photoreceptors and retinal pigment epithelial (RPE) cells in the parapapillary region. This study investigated whether glaucomatous changes of the deep retinal layer occur outside the parapapillary region. The nuclei of the retinal photoreceptors and RPE cells were counted in histologic slides of 23 eyes with painful secondary angle-closure glaucoma resulting from perforating corneal injuries. Fourteen eyes with malignant choroidal melanoma not involving the ciliary body or trabecular meshwork served as the control group. No surgical procedure, including laser treatment, had been performed posterior to the ora serrata. There were no hints of retinal vessel occlusion and localized traumatic retinopathy, historically, ophthalmoscopically, or histologically. Photoreceptor count was significantly lower (P less than 0.05) in the glaucoma eyes than in the control group. Count of RPE cells did not differ between the two groups. This may indicate that glaucoma can be associated with a loss of photoreceptors. This could be important for psychophysical testing and may point to a more widespread involvement of ocular tissues in glaucoma than believed. PMID- 1634351 TI - Impact of androgen therapy in Sjogren's syndrome: hormonal influence on lymphocyte populations and Ia expression in lacrimal glands of MRL/Mp-lpr/lpr mice. AB - Recent research has demonstrated that androgen treatment dramatically curtails lymphocyte infiltration in the lacrimal glands of a mouse model of Sjogren's syndrome. The purpose of the current study was to determine whether this androgen action involves the selective suppression of specific lymphocyte populations or Ia expression in lacrimal tissue. Autoimmune female MRL/Mp-lpr/lpr mice were administered placebo- or testosterone-containing compounds for 0, 17, or 34 d. Then lacrimal glands were obtained and processed for immunohistochemical evaluation. Results demonstrated that in pretreatment mice, lacrimal lymphoid foci were composed predominantly of Thy 1.2+ cells, bearing L3T4 (helper T cell) or B220 surface antigens. In contrast, suppressor T cells (Lyt 2+) and surface IgM-bearing B cells represented minority populations in the immune infiltrates. Class II antigen (Ia) expression was observed on over 40% of the infiltrate lymphocytes and occasionally on epithelial cells close to the lymphoid focus. During the experimental time course, the extent of lymphocyte infiltration increased in glands of placebo-treated mice. This cellular accumulation was associated with an elevation in the frequency of B220+ cells, but not that of other lymphocyte subclasses. Testosterone administration induced a striking diminution in the area encompassed by all immune cell populations. Moreover, hormone therapy significantly reduced the frequency of B220+ cells in focal infiltrates. Overall, these findings demonstrate that androgen exposure stimulates a decrease in the quantity, but not necessarily the entire lymphocyte composition, of lymphoid aggregates in lacrimal glands of MRL/lpr mice. PMID- 1634352 TI - Extracellular matrix in aged human ciliary body: an immunoelectron microscope study. AB - Tissue from nine human eyes (ages 52-78 yr) was used to investigate the fine structural distribution of collagens I-VI and laminin in the ciliary body using the immunogold antibody labeling technique. The anterior segments of the specimens were normal, and the eyes were removed in treatment of choroidal melanoma. The basement membranes of the ciliary epithelium contained collagens I, III, and IV. Laminin was in greater concentration in the outer part of the nonpigmented epithelial basement membrane, and the distribution suggested a washout effect. The zonular apparatus labeled intensely with laminin. In contrast, laminin was not present in the basement membrane of the myocytes in the ciliary body. These cells were sheathed in a basement membrane that contained types I, III, and IV collagen. Plaque-like structures of slightly different morphology (a, filamentous; b, granular; c, amorphous) were found in the tendinous insertions, and subtypes a and b were strongly labeled with laminin. The basement membranes of the vessels contained types I and IV collagen, but laminin labeling was inconclusive. The major finding was that the lamina densa in the basement membranes of various sites labeled for collagens I, III, and IV. Striated collagen fibrils in the stroma were labeled for types I and III. Collagen subtypes V and VI were not identified in significant quantity in any of the regions examined. PMID- 1634353 TI - Mitochondrial DNA mutation in Leber's hereditary optic neuropathy. AB - Leber's hereditary optic neuropathy (LHON) causes acute or subacute central visual loss in healthy young males. Recently, it has been thought to be caused by a single nucleotide change in the ND4 gene in the mitochondrial genome. Mitochondrial DNA (mtDNA) of leukocytes and hair follicle cells from five patients in four families with LHON and nine relatives were analyzed by Sfa NI and Mae III enzyme digestion and DNA sequencing. Loss of Sfa NI site was found in all patients and maternal lineages but not in nonmaternal lineages and normal controls. Mae III digested all the mtDNAs that lost the Sfa NI site. The restriction fragment pattern of polymerase chain reaction (PCR) products exhibited mtDNA heteroplasmy in the hair follicle cells but not in blood cells of the proband in one family. Direct sequencing of PCR-amplified mtDNA fragments encompassing the ND4 gene of the patients disclosed a transition from guanine to adenine at nucleotide position 11778. These results confirm previous reports that a G to A point mutation is associated with LHON and that tissue variability and heteroplasmy of mtDNA exist in some, but not all, LHON patients. PMID- 1634354 TI - Unusually low values of mannitol permeability (PM) of the corneal epithelium and endothelium. PMID- 1634355 TI - Hb Kanagawa [alpha 40(C5)Lys----Met]: a new alpha chain variant with an increased oxygen affinity. AB - An abnormal hemoglobin was suspected in a 70-year-old Japanese male with cerebral infarction and erythremia with high performance liquid chromatography assay of Hb A1c. The hemoglobin variant migrated to the anode more rapidly than Hb A. Structure determination studies, including amino acid analysis of the abnormal peptide and DNA sequencing of a partially cloned alpha-globin gene, demonstrated that it is a new hemoglobin variant which has been named Hb Kanagawa [alpha 40(C5)Lys----Met]. This variant showed an increased oxygen affinity, decreased heme-heme interaction, and a lowered 2,3-diphosphoglycerate effect relative to normal. PMID- 1634356 TI - Anthropology of the beta S gene-flow from West Africa to north Africa, the Mediterranean, and southern Europe. PMID- 1634357 TI - A new alpha chain variant, Hb Turriff [alpha 99(G6)Lys----Glu]: the interference of abnormal hemoglobins in Hb A1c determination. AB - Hb Turriff is a new hemoglobin variant which we have identified in a diabetic individual. During the determination of Hb A1c by high performance liquid chromatography, an inappropriately elevated result was found to be due to the abnormal hemoglobin chromatographing with the Hb A1c fraction. This new hemoglobin variant, Hb Turriff [alpha 99(G6)Lys----Glu], is not associated with any hematological disturbance, and family investigations indicate that it has arisen as a de novo mutation. PMID- 1634358 TI - Hb Kaohsiung or New York: a T----A substitution at codon 113 of the beta-globin chain creates an Alu I cutting site. PMID- 1634359 TI - The unstable Hb Hammersmith or alpha 2 beta 2(42)(CD1)Phe----Ser observed in an Indian child; identification by HPLC and by sequence analysis of amplified DNA. AB - We have identified the unstable hemoglobin variant present in a Chipewayan Indian patient with severe hemolytic anemia as Hb Hammersmith or alpha 2 beta 2(42)(CD1)Phe----Ser. Her parents were normal. Identification was greatly facilitated by the use of reversed phase high performance liquid chromatography for the isolation of the beta X chain and its tryptic fragments, and of sequence analysis of amplified DNA which readily identified a TTT(Phe)----TCT(Ser) mutation at codon 42. PMID- 1634360 TI - Hb Rancho Mirage [beta 143(H21)His----Asp]; a variant in the 2,3-DPG binding site showing normal oxygen affinity at physiological pH. AB - Hb Rancho Mirage was detected in a 17-year-old male in association with a mild anemia. Hemoglobin electrophoresis revealed the variant had a mobility between Hbs A and J on cellulose acetate (pH 8.6) and a mobility like Hb F on citrate agar (pH 6.4). A substitution of His----Asp was found at position 143 in the beta chain, a residue that contributes to the anionic 2,3-DPG binding site in Hb. This variant exhibited normal oxygen affinity at physiologic pH and reduced affinity at alkaline pH. This suggested a subtle shift in the allosteric equilibrium due most likely to the introduction of a negative charge that stabilized the 2,3-DPG pocket. Both homotrophic (heme-heme) and heterotropic (2,3-DPG and protons) effects were reduced; this might be a consequence of an alteration in the carboxyl terminal region of the beta-subunits. Although a His----Asp substitution would be considered to cause reasonable disruption of the 2,3-DPG and C-terminal conformation of the beta- subunits, the properties of Hb Rancho Mirage suggest that, in fact, there appear to be no major perturbation of the critical C terminal residues. PMID- 1634361 TI - The nondeletional types of Hb H disease in Guangxi. AB - Three primers were designed, one specific for alpha 1-globin DNA, a second for alpha 2-globin DNA, and a third that is common for both alpha 1- and alpha 2 globin DNA. These three primers can be applied for selective amplification of the two globin DNA fragments, which is useful for identification of nondeletional types of Hb H disease. Fifty-nine DNA samples of Hb H patients from Guangxi were studied by selective amplification, and 27 cases (45.8%) were confirmed as nondeletional types. Of these, 22 (81.5%) had the Hb Constant Spring (CS) mutation and one had the Hb Quong Sze (QS) mutation; both were identified by hybridization with synthesized oligonucleotide probes. Nondeletional Hb H disease in Guangxi seems to be more severe than the deletional types. The average hemoglobin level of the nondeletional Hb H/CS (--/alpha alpha) is 6.8 g/dl, which is lower than that of the deletional types (7.9 g/dl), while the levels of Hb H and Hb Bart's were much higher in the patients with Hb H/CS than in those with the deletional types. PMID- 1634362 TI - Types of thalassemia among patients attending a large university clinic in Kuala Lumpur, Malaysia. AB - We have identified the beta-thalassemia mutations in 59 patients with thalassemia major and 47 patients with Hb E-beta-thalassemia, and the deletional and nondeletional alpha-thalassemia determinants in 23 out of 24 patients with Hb H disease. All persons were attending the Haematology Clinic at the National University of Malaysia in Kuala Lumpur (Malaysia). Most patients (76) were of Malay descent, while 52 patients were Chinese, and two came from elsewhere. The most frequently occurring beta-thalassemia alleles among the Malay patients were IVS-I-5 (G----C) and G----A at codon 26 (Hb E), while a few others were present at lower frequencies. The Chinese patients carried the mutation characteristic for Chinese [mainly codons 41/42 (-TTCT) and IVS-II-654 (C----T)]; Malay mutations were not observed among Chinese and Chinese mutations were virtually absent in the Malay patients. The large group of patients with Hb E-beta thalassemia and different beta-thalassemia alleles offered the opportunity of comparing hematological data; information obtained for patients with Hb E-beta thalassemia living in other countries was included in this comparison. Twenty three patients with Hb H disease carried the Southeast Asian (SEA) alpha thalassemia-1 deletion; 13 had the alpha CS alpha (Constant Spring) nondeletional alpha-thalassemia-2 determinant, while the deletional alpha-thalassemia-2 (-3.7 or -4.2 kb) was present in 10 subjects. The --/alpha CS alpha condition appeared to be the most severe with higher Hb H values. Both deletional and nondeletional types of alpha-thalassemia-2 were seen among Malay and Chinese patients. PMID- 1634363 TI - A new alpha chain variant, Hb Hanamaki or alpha 2(139)(HC1)Lys----Glu beta 2, found in a Japanese family. PMID- 1634364 TI - Hb Olomouc [alpha 2 beta 2(86)(F2)Ala----Asp] found in a Japanese family. PMID- 1634365 TI - Hb Nottingham or alpha 2 beta 2(98)(FG5)Val----Gly observed as a de novo mutation in a Canadian child. PMID- 1634366 TI - Hb Hope [beta 136(H14) Gly----Asp] and Hb E [beta 26(B8)Glu----Lys]: compound heterozygosity in a Thai Mien family. PMID- 1634367 TI - Hb Kodaira [beta 146(HC3)His----Gln]: a new beta chain variant with an amino acid substitution at the C-terminus. PMID- 1634368 TI - Three beta-thalassemia mutations in the Japanese: IVS-II-1 (G----A), IVS-II-848 (C----G), and codon 90 (GAG----TAG). PMID- 1634369 TI - A new case of thalassemia intermedia: interaction of a triplicated alpha-globin locus and beta-thalassemia trait. PMID- 1634370 TI - Proteoglycan and collagen morphology in superficially scarred rabbit cornea. AB - We have examined the changes in collagen and proteoglycan morphology in superficial lamellar keratectomy wounds produced in rabbit corneas. The ultrastructural location within the tissue of keratan sulphate and chondroitin sulphate proteoglycans was demonstrated using the cationic dye Cuprolinic Blue under critical electrolyte conditions. Large proteoglycan filaments (up to 500 nm long) appeared in the early stages of wound healing; these were most common after two weeks' wound healing, after which they decreased both in number and size. At these early stages of scar formation, spaces containing proteoglycans were present amongst bundles of collagen fibrils. As proteoglycans play an important role in controlling corneal hydration, the presence of the large proteoglycan filled spaces would result in an abnormally high water content which is found in early scar tissue. PMID- 1634372 TI - Histochemical analysis of rat testicular glycoconjugates. 2. Beta-galactosyl residues in O- and N-linked glycans in seminiferous tubules. AB - Rat testes have been examined with a panel of lectins that bind specifically to oligosaccharide sequences having terminal or subterminal beta-galactosyl residues in O-linked glycans, or in the outer chains of complex N-linked glycans: Arachis hypogaea (peanut, AHA), Erythrina cristagalli (coral tree, ECA), Ricinus communis (castor bean, RCA120) and Abrus precatorius (jequirity bean, APA) agglutinins. Pretreatment of sections with neuraminidase, beta-galactosidase and removal of alkali-labile O-linked sequences by beta-elimination allowed the structure of these glycans to be further explored. In spermatogonia and spermatocytes there was little evidence of glycans terminating in beta-galactosyl residues, although these were present at non-reducing terminals as sialylgalactosides. The acrosome contained two subsets of O-linked glycans terminating in sialylgalactosides, while the nuclear cap showed at least two subsets of N-linked sialylgalactosyl as well as O-linked glycans. Spermatozoa exhibited minor changes in the pattern of glycosylation, although the overall pattern of beta-galactosyl expression was similar. Binding to Sertoli cells showed the presence of some unsubstituted beta galactosyl terminals on O-linked glycans but few such N-linked residues, while terminal beta-galactosides were scanty in tubular basement membranes. PMID- 1634371 TI - Histochemical analysis of rat testicular glycoconjugates. 1. Subsets of N-linked saccharides in seminiferous tubules. AB - The distribution of N-linked glycans in rat testis has been probed using a panel of lectins derived from Galanthus nivalis (snowdrop, GNA), Canavalia ensiformis (jack bean, Con A), Lens culinaris (lentil, LCA), Pisum sativum (garden pea, PSA) and Phaseolus vulgaris, erythro- and leucoagglutinins (kidney bean, ePHA and lPHA). Several classes of N-linked glycan were identified in the spermatogenic series, and during differentiation into spermatozoa they altered in both their pattern of distribution and relative abundance. A population of tetra-antennary, non-bisected, complex glycans, detected by lPHA, was lost during the transition from spermatogonia to spermatocytes, while high-mannose structures were acquired; these were most abundant in spermatocytes, as were bi- and tri-antennary complex, non-bisected glycans, the latter becoming increasingly abundant on acrosomes and spermatozoa. Their bisected counterparts were more generally expressed throughout spermatogenic cells, although marked localization onto acrosomes and nuclear caps was again seen. Transition from spermatocytes to spermatids involved mainly changes of the acrosomal granule and nuclear cap, which were carried through to the final stages of differentiation. Sertoli cell surfaces and cytoplasmic granules showed a high level of N-glycan expression. PMID- 1634373 TI - Carbohydrate and protein histochemistry during oogenesis in Halobatrachus didactylus (Schneider, 1801) from the Bay of Cadiz (Spain). AB - Histological and histochemical characteristics were studied in Halobatrachus didactylus (Schneider, 1801) during oogenesis. Three phases could be differentiated: previtellogenesis (oogonia and basophilic oocytes), vitellogenesis (yolk synthesis) and maturation-spawning. Glycogen, glycoproteins and proteins rich in certain amino acids were present in the previtellogenic as well as in the vitellogenic cytoplasm oocytes. No acid mucosubstances were detected. Three types of yolk (vesicles, vacuoles and granules) contained different types of organic reserves; granules were essentially proteic whereas globules were lipidic. Carbohydrates and proteins were present in vesicles. PMID- 1634374 TI - Changes in lectin binding patterns of Leydig cells during fetal and postnatal development in mice. AB - Changes in the lectin binding of mouse Leydig cells during fetal and postnatal development were examined by light- and electron-microscopy using eight different biotinylated lectins (ConA, WGA, RCA-I, UEA-I, GS-I, PNA, SBA and GS-II). At the light-microscopic level, ConA, WGA, RCA-I, UEA-I and GS-I showed the same binding pattern in which all five lectins bound to the plasma membrane and cytoplasm of Leydig cells from the 13th day post coitum (p.c.) to the 8th postnatal week. PNA, SBA and GS-II reactions were positive in the plasma membrane and cytoplasm of Leydig cells from the 13th day p.c. to 15th day post partum (p.p.) but disappeared completely by day 20. At the electron-microscopic level, gold particles representing the GS-I or GS-II binding sites were distributed primarily along the cell surface membrane, including that of microvilli, as well as in the cytoplasm. These results indicate that certain glycoconjugates bearing D galactose, N-acetyl-D-galactosamine, and N-acetyl-D-glucosamine residues are expressed on the cell surface and in the cytoplasm of Leydig cells during the period from the 13th day p.c. to around the 20th day p.p. The results suggest that these glycoconjugates might play some role in modulating hormone-receptor interaction in the Leydig cells before the 20th day. Furthermore, these results may indicate that sugar residues expressed on the cell surface and in the cytoplasm of Leydig cells are different from those in the fetal-neonatal and adult phases. PMID- 1634375 TI - Structural variations of different oral basement membranes revealed by cationic dyes and detergent added to aldehyde fixative solution. AB - The ultrastructural appearance of different types of basement membrane was studied using histochemical methods for visualizing glycosaminoglycans. Samples of rat gingiva and mouse molar germ tissue were fixed either with glutaraldehyde, glutaraldehyde-ruthenium hexammine trichloride (RHT), glutaraldehyde-Cuprolinic Blue (CB) or cetylpyridinium chloride-glutaraldehyde (CPC). Ultrathin sections were stained with uranyl acetate and lead citrate. The results showed that the conventional trilaminar structure of the basement membrane was observed after glutaraldehyde and CB fixation. In contrast, after CPC or RHT fixation, the appearance of the basement membrane was homogeneous without any evidence of a lamina lucida. Furthermore, after single fixation with CPC, the ultrastructure of different basement membranes from oral tissues showed some differences in appearance which were related to their localizations, functions, or both. PMID- 1634377 TI - [The Romberg head-shake test within the scope of equilibrium diagnosis]. AB - We review the standard functional tests of static and dynamic equilibrium and discuss the value of these tests. The pendular platform test and the tilting table test were developed for provocation of the balance system, but are not used in clinical investigation because of the complicated apparatus and the difficulties of judgement of the curves recorded. A simple modification for provocation of the balance system, available in the clinic, the consulting room or the doctor's office is recommended, consisting of horizontal head-shaking in the Romberg position during posturographic recording. In healthy subjects little increase of body sway is found, but in patients with peripheral or central vestibular disorders a distinct tendency of disequilibrium is seen. PMID- 1634376 TI - Immunocytochemical study of dystrophin in cultured mouse muscle cells by the quick-freezing and deep-etching method. AB - Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene, is deficient in patients with DMD and in mdx mice. It is immunocytochemically localized in skeletal muscle sarcolemma. However, little is known about the three dimensional ultrastructural localization of dystrophin and its relationship with other cytoskeletal proteins. We found that dystrophin is localized irregularly, just underneath the plasma membrane in normal cultured mouse myotubes, by using the quick-freezing and deep-etching (QF-DE) method; it was found to be closely linked to actin-like filaments (8-10 nm in diameter), most of which were decorated with myosin subfragment 1, and was attached to the cytoplasmic side of the plasma membrane. These results suggest that dystrophin might play an important role in the preservation of cell membrane stability by connecting actin cytoskeletons with the cytoplasmic side of the plasma membrane. PMID- 1634378 TI - [Computer-assisted ENT medical literature search and literature management--a report of experiences]. AB - The increasing number of medical articles calls for a computer-aided system for literature database programs, literature retrieval and bibliography systems. We report an assessment of a dedicated modem line to DIMDI of Cologne (an institute offering a variety of biomedical, psychological and other literature databases), Medline on Silverplatter, Current Contents on disk and the Papyrus bibliography system. The databases with retrieval software are installed on a IBM-compatible PC (386 with an 80MB hard disc) and 4 CD-ROM players. Medline contains bibliographic citations and abstracts of biomedical literature; Current Contents on disk with its weekly update provides citations of articles published very recently; and the Papyrus bibliography system maintains a permanent collection of reference citations. When linked to a word processor, Papyrus can automatically read the manuscript, create a bibliography and produce a new copy of the manuscript in which the citations have been appropriately edited, and the references can be printed in any desired format. Although not without drawbacks, the configuration described here proved to be a valuable, time-saving tool to access citations precisely. PMID- 1634379 TI - [The temporal bone]. AB - Imaging of the temporal bone by high resolution CT scan has become more and more accurate in recent years. Coronal slices are particularly important. We present the anatomy of four temporal bones embedded in plastic material. Coronal sections with a thickness of 2 mm were taken, radiographed and their density measured. Particular interest was given to the three-dimensional relations as well as to the density of bone of important morphological structures such as the labyrinth, middle ear, facial canal, sigmoid sinus, carotid canal and the mastoid. A low density of bone corresponds to the colour blue, a high density to black. Because of the high resolution of the method it was possible to image small and fine structures such as the auditory ossicles, and the perilymphatic and endolymphatic ducts. A three-dimensional reconstruction may well be possible in the future, and the possibilities of this method are discussed. PMID- 1634380 TI - [Marginal cells of the stria vascularis in vitro]. AB - Explants of stria vascularis and spiral ligament of the guinea pig cochlea were cultivated and after 2 days fibroblast-like cells were found growing around the explant. Marginal cells advanced at 15 microns/day to the border of the explant, and after 2 weeks they proliferated on top of a thin layer of fibroblast-like cells outside the explant, replacing several layers of fibroblast-like cells. Tight junctions and interdigitations of the lateral membranes were found between all neighbouring marginal cells. Their apical surface was covered by microvillus like membrane extensions. The basal membrane of the new marginal cells did not interdigitate with the underlying membranes of fibroblast-like cells; there was always a gap between the two cell types. The results demonstrate that marginal cells of the stria vascularis are capable of repairing damage to the epithelium, such as may be caused by endolymphatic hydrops, even if the luminal side contains perilymph-like fluid. Furthermore, the cell culture allows living, clearly identified marginal cells to be studied in vivo. PMID- 1634381 TI - [Resection of the semicircular canal system with preserved hearing--an animal experiment study]. AB - In a previous investigation we selectively resected the lateral semicircular canal of the rabbit, preserving the hearing in 67% of the animals. We now report an attempt to remove all three canals in one step with a microsurgical technique using fibrin glue and bone chips. Brain-stem auditory potentials were recorded at intervals up to 3 months after operation. Residual hearing could be recorded in 50% of rabbits. These animals regularly showed a 30-40 dB deterioration of hearing. PMID- 1634382 TI - [Diagnosis of energy metabolism in ENT tumors--a PET study]. AB - The metabolism of malignant tumours can be determined in vivo by positron emission tomography. Fifty patients with malignant lesions of the head and neck were examined before therapy and followed up for 11-18 months. The course of the disease was related to the initial fluorodeoxyglucose (FDG) uptake of the tumour. There was a relation between FDG uptake and survival: an increased FDG uptake of more than 300-400% was related to a reduced survival rate. Patients with an uptake less than 300% had a much better prognosis. PMID- 1634383 TI - [Indications and surgical treatment of large middle ear abnormality]. AB - Children with atresia of the external auditory canal should undergo hearing assessment and fitting of a bone conduction hearing aid as early as possible to allow speech to develop normally. Surgery is done between 5 and 6 years of age, guided by high-resolution computed tomography, which provides a more precise diagnosis based on the abnormalities seen. The temporomandibular joint lies more posteriorly than normal due to aplasia or hypoplasia of the tympanic bone, so that the middle ear must be approached through the mastoid, resulting in a less favourable coupling to the middle ear structures. In unfavourable cases bone anchored hearing aids, creation of a meatus for fitting a hearing aid or a bone conduction hearing aid must be considered. PMID- 1634384 TI - [Audit of maternal and delivery records]. PMID- 1634385 TI - [How to diagnose pregnant women with drug abuse problems and which ones need support]. PMID- 1634386 TI - [Description of family social monitoring activities]. PMID- 1634387 TI - [World Health Organization reinforces the code of ethics on marketing of human milk substitutes]. PMID- 1634388 TI - Lactation characteristics of nine breeds of cattle fed various quantities of dietary energy. AB - Milk yield data were collected by weigh-suckle-weigh procedures at approximately 14, 28, 56, 84, 112, 138, 156, 184, and 212 d postpartum for mature Angus, Braunvieh, Charolais, Gelbvieh, Hereford, Limousin, Red Poll, Pinzgauer, and Simmental cows over a 4-yr period. Individual cows were fed at one of four energy intake levels. Parameters characterizing lactation curves for 431 lactations from 179 cows were estimated by nonlinear regression. Differences due to breed, level of energy intake, and the two-factor interaction between breed and level of ME allowance for scale and shape parameters of lactation curves and derived estimates for time of peak lactation, yield at time of peak lactation, and for total yield for a 210-d lactation period were evaluated. Breed and energy intake level were significant sources of variation for all traits. Pooled over energy levels, daily yields at time of peak lactation of Braunvieh, Gelbvieh, and Pinzgauer were greater (P less than .05) than those of Angus, Charolais, Hereford, and Limousin. Simmental and Red Poll were intermediate. Total lactation yield of the Braunvieh exceeded (P less than .05) that of all other breeds with the exception of Gelbvieh. Hereford produced less milk than (P less than .05) the other breeds. The response in yields at time of peak lactation as energy allowances increased for Braunvieh, Charolis, Gelbvieh, Limousin, and Pinzgauer cows were linear and resulted in higher yields at this time. Linear increases in total 210-d yield and times of peak lactation were observed for all breeds with the exception of Hereford. PMID- 1634389 TI - The effect of body condition, live weight, breed, age, calf performance, and calving date on reproductive performance of spring-calving beef cows. AB - Data from 321 spring-calving cows (mean calving date March 27) were used to assess the effects of body condition, live weight, cow age (from 4 to 13 yr), and breed (237 Hereford x Friesians and 84 Blue-Greys) and time of calving on the proportion of cows that became pregnant, the number of days from the start of mating to pregnancy, and calving interval. Mating started at turn-out to pasture in mid-May and lasted 9 to 10 wk. Body condition at calving and breed were the most significant animal factors affecting reproductive performance. Cows calving in higher body condition had shorter (P less than .001) calving intervals (11.2 d per unit of body condition at calving). Blue-Grey cows became pregnant in a higher proportion (90%) and calving interval was shorter (364 d) than in Hereford x Friesians (83%; 374 d). Body condition at the start of mating was less important and body condition at the end of mating had no effect. Live weight at calving and changes in live weight from calving to the start of mating and during the mating period had no significant effect. The proportion of cows becoming pregnant decreased significantly with age in Hereford x Friesian cows older than 7 yr. The variance in calving interval accounted for by calving date, body condition at calving, breed, and age was 42%. PMID- 1634390 TI - Live animal measurement of carcass traits by ultrasound: assessment and accuracy of sonographers. AB - The establishment and evaluation of an assessment system to accredit sonographers for measuring the carcass traits of subcutaneous fat depths and longissimus muscle area (LMA) on potential breeding animals by real-time ultrasound is described. Repeatability of operators, variation between the animal's left and right sides, and variations in technique were assessed from measurements and repeat measurements of 30 cattle by up to eight operators at three testing sessions. Accuracy of carcass data was determined by repeatability of measurements, variability between measurers, between left and right sides of the carcass, and variation due to handling and dressing procedures. Correlations with carcass data averaged .92 for rump fat, .90 for rib fat, and .87 for LMA. Residual SD averaged .81 mm, .88 mm, and 5.1 cm2. A very experienced sonographer can measure LMA only marginally less accurately than it can be measured on the carcass. In Session 3, the SE between repeat fat measurements for accredited sonographers averaged .43 mm, indicating that fat depths can be measured more accurately, but when comparing measurements from different operators, adjustments may be required for differences in technique, otherwise overall accuracy will be about the same, approximately 1 mm. Scanned rump fat measurements were consistently approximately 20% higher than on the chilled, hanging carcass 24 h after slaughter; after applying the standard correction factor of 1.17, LMA measurements were similar. Scan and carcass rib fat measurements were similar for animals with less than or equal to 10 mm of fat cover, above which carcass measurements tended to be higher. PMID- 1634391 TI - Subclinical mastitis in ewes and its effect on lamb performance. AB - Two studies were conducted to 1) assess the effectiveness of the California mastitis test (CMT) relative to direct microscopic somatic cell count (DMSCC) and(or) somatic cell count (SCC) procedures for detecting subclinical mastitis in ewes, 2) determine the incidence of subclinical mastitis based on repeated or single sample measures and organisms associated with the inflammation, and 3) assess the relationship between milk quality measures and lamb performance. The relationship between DMSCC and SCC scores was significant (P less than .01); 90% of the variation in DMSCC scores was accounted for by SCC scores. In contrast, CMT scores accounted for only 26% of the variation in DMSCC and 30 to 34% of the variation in SCC scores. Incidence of inflammation varied from 17 to 50% of ewes tested, depending on the study and the method of assessment. Staphylococcus species were cultured from 14/41 samples tested, with cultures of Streptococcus species (3/41) and Micrococcus species (1/41) also present. The effect of subclinical mastitis in ewes on lamb performance was minimal when assessed by regressing lamb weights on subclinical mastitis and milk quality scores. In conclusion, growth performance of lambs in a management system where they had access to supplemental feed was not influenced by the quality of milk produced by ewes, or by the degree of subclinical mastitic inflammation present when they suckled. PMID- 1634392 TI - Influence of yeast culture on feeder calves and lambs. AB - Four experiments were conducted to determine the influence of yeast culture on 1) the health and performance of feeder calves, 2) the response of calves to an infectious bovine rhinotracheitis virus (IBRV) infection, and 3) nutrient utilization in lambs fasted for 3 d. In Exp. 1, 108 feeder calves were transported from Tennessee to Texas (1,600 km) and fed receiving diets containing 0 or .75% yeast culture and .35 or .69% P in a 2 x 2 factorial arrangement of treatments. In Exp. 2, 101 calves were transported 950 kg from Austin, TX to Bushland, TX and fed receiving diets containing 0, .75, 1.125, or 1.5% yeast culture. Yeast culture did not significantly affect the health or performance of calves in either experiment, although morbid calves fed yeast culture required fewer (P less than .05) days of antibiotic therapy in Exp. 2. In Exp. 3, feeder steers were fed diets containing 0 or .75% yeast culture and challenged intranasally with IBRV. Calves fed yeast culture tended to maintain heavier weights and higher DMI during IBRV infection than did steers fed the control diet. In Exp. 4, feeder lambs were fasted for 3 d and refed diets containing 0, .75, 1.125, or 1.5% yeast culture during a N and mineral balance trial. Lambs fed yeast culture had greater (P less than .08) N balance and tended to have greater Zn and Fe balance than control lambs. Results of these studies are interpreted to suggest that supplementation of morbid calves with yeast culture can have beneficial effects (fewer sick days, higher feed intakes) and that these effects may be mediated by improved N, Zn, and Fe metabolism. PMID- 1634393 TI - Feedlot performance of steers and bulls actively immunized against gonadotropin releasing hormone. AB - Feedlot performance and testicular and pituitary function were assessed in cattle actively immunized against GnRH. In Trial 1, 50 steers were either unimmunized (n = 10), actively immunized against keyhole limpet hemocyanin (KLH; n = 10), or immunized against a GnRH-KLH conjugate (n = 30). Fifteen of 30 steers immunized against GnRH-KLH received a secondary immunization 8 wk after primary immunization. Antibodies against GnRH were not evident in unimmunized steers or steers actively immunized against KLH. Antibodies against GnRH were noted in all immunized animals (n = 30) within 6 wk of primary immunization and anti-GnRH antibody concentrations became maximal 20 to 24 wk after immunization. The increasing anti-GnRH titer in immunized steers was associated with decreasing serum concentrations of LH. Serum concentrations of LH were depressed (P less than .05) within 8 wk of primary immunization and reached a nadir by wk 20. The patterns of increase in GnRH titer and decrease in serum concentrations of LH did not differ (P greater than .05) in animals receiving primary immunization alone or primary and secondary immunization. Feedlot performance and carcass quality were not affected (P greater than .05) by immunization against KLH or the GnRH KLH conjugate. In Trial 2, 60 bull calves (mean weight = 325.2 +/- 2.8 kg) were randomly assigned to a 2 x 3 factorial experiment. The two classes (n = 30) were 1) unimplanted and 2) implanted with Synovex-S. The three treatments (n = 20) were 1) intact control, 2) actively immunized against GnRH, and 3) castrate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634394 TI - Effect of zeranol implants in ram and wether lambs on performance traits, carcass characteristics, and subprimal cut yields and distribution. AB - In two separate 2 x 2 factorial arrangements, 69 male, crossbred lambs were allotted randomly to the following treatments: 1) nonimplanted (NI) rams, 2) implanted (I) rams, 3) NI wethers, and 4) I wethers. In Trial 1, 36 lambs were allotted to treatment groups at birth (n = 9) and I lambs were implanted with 12 mg of zeranol between 1 and 3 d of age and again at weaning (average age of 62 d). Lambs were slaughtered at three time-constant end points of 78, 93, and 107 d on feed postweaning (average age of 155 d). Rams grew faster postweaning, were more efficient in their feed conversion, were heavier at slaughter, and had lower numerical yield grades than did wethers (P less than .05). Implanted lambs tended (P = .08) to grow faster and were (P less than .05) more efficient in their feed conversion than NI lambs. Rams produced heavier (P less than .05) trimmed subprimal shoulders, loins, and legs and had (P less than .05) a higher percentage of their carcass weight in the subprimal shoulder than did wethers. During Trial 2, NI rams (n = 8), I rams (n = 8), NI wethers (n = 8), and I wethers (n = 9) were allotted to treatment groups, and I lambs were implanted at average ages of 14, 55, and 98 d. After weaning, lambs were weighed every 14 d and were slaughtered 7 d after reaching a minimum weight of 50 kg (average age of 148 d).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634395 TI - Genotype and treatment biases in estimation of carcass lean of swine. AB - Carcasses of 181 barrows, representing five genotypes, 1) H x HD, 2) SYN, 3) HD x L[YD], 4) L x YD, and 5) Y x L (H = Hampshire, D = Duroc, SYN = synthetic terminal sire line, L = Landrace, and Y = Yorkshire), and two levels of ractopamine (RAC) treatment (0 and 20 ppm) were completely dissected and the data were used to examine genotype and treatment (RAC) biases in estimation of fat standardized lean weight and to evaluate accuracies and precisions realized by use of equations based on variables derived from different technologies. Independent variables used to establish regression equations represented technologies of direct carcass measurements, optical probe data, TOBEC (total body electrical conductivity) readings, and dissected (DHMLN) and fat standardized (FSHMLN) ham lean. Genotype bias existed when any equation from a single technology was used and was minimized by combining FSHMLN with one TOBEC reading, carcass length, and the probe measurement of 10th rib fat depth. Large RAC biases appeared when equations from direct carcass measurements or optical probe data were used and were minimized by an equation using either DHMLN or FSHMLN. A practical equation with relatively high R2 value and small genotype and RAC biases were developed by combining TOBEC readings with direct carcass measurements of 10th rib fat depth and warm carcass weight. PMID- 1634396 TI - Growth, development, and carcass composition in five genotypes of swine. AB - An experiment with 127 barrows representing five genotypes, 1) H x HD, 2) SYN, 3) HD x L[YD], 4) L x YD, and 5) Y x L (H = Hampshire, D = Duroc, SYN = synthetic terminal sire line, L = Landrace, and Y = Yorkshire), was conducted to evaluate growth and development of swine from 59 to 127 kg live weight. Animals were allowed ad libitum access to a pelleted finishing diet containing 18.5% CP, .95% lysine, and 10.5% fat, with an energy density of 3,594 kcal of ME/kg. Pigs were serially slaughtered at either 59, 100, 114, or 127 kg live BW. After slaughter, carcasses were chilled and backfat was measured at four locations. The right side of each carcass was fabricated into primal cuts of ham, loin, Boston Butt, picnic, and belly. Composition of each primal cut was determined by physical dissection into lean, fat, bone, and skin. Estimated allometric growth coefficients for carcass length, carcass weight, and longissimus muscle area relative to BW; carcass lean, fat, bone, and skin relative to both BW and carcass weight; and lean in each of the primal cuts relative to total carcass lean did not differ (P greater than .05) among genotypes. Relative to BW, the pooled growth coefficient(s) for carcass weight was (were) greater (P less than .001) than unity, whereas those for carcass length, longissimus muscle area, and backfat at first rib were smaller (P less than .001) than unity. Those for other backfat measurements were close to 1.00. Relative to either BW or carcass weight, the pooled coefficient(s) for fat was (were) greater (P less than .001) than unity, whereas those for lean, bone, and skin were smaller (P less than .001) than unity. Growth of lean, backfat, bone, and skin in the carcass were nearly linearly associated with increases in BW. The increase in fat weight was curvilinear as the pig grew and was accelerated in later growth stages, indicating that carcass fat percentage increased with increased BW. PMID- 1634397 TI - Reduced animal model with differential genetic grouping for direct and maternal effects. AB - Mixed-model equations for the reduced animal model with maternal effects and different genetic grouping of unknown parents for additive direct and maternal effects are derived. The matrices that relate the expected value and the variance of the breeding values of non-parents to the parents, as well as the different contributions of parental and non-parental breeding values, to the resulting mixed-model equations are presented. Mis-specification of additive maternal variance and the additive covariance between direct and maternal effects, arising from missing information on the dams of known individuals with records, is discussed. To avoid an incorrect specification of the variance-covariance matrix of the records without having to invert a nondiagonal variance of the residual terms, the breeding values of the unknown dams of individuals with records are included in the equations. Breeding values of non-parents are back-solved after the solutions for genetic groups and breeding values of parents are computed as simply as in cases in which maternal effects are absent. A numerical example is included to illustrate the derivations. PMID- 1634398 TI - Breed effects and heterosis in advanced generations of composite populations on actual weight, adjusted weight, hip height, and condition score of beef cows. AB - Heterosis effects were evaluated in three composite populations in F1, F2, and F3 generations separately and combined in 1-yr-old and from 2- through greater than or equal to 7-yr-old beef cows. Traits included actual weight, weight adjusted to a common condition score, hip height, and condition score. Breed effects were evaluated in the nine parental breeds (Red Poll [R], Hereford [H], Angus [A], Limousin [L], Braunvieh [B], Pinzgauer [P], Gelbvieh [G], Simmental [S], and Charolais [C]) that contributed to the three composite populations (MARC I = 1/4 B, 1/4 C, 1/4 L, 1/8 H, 1/8 A; MARC II = 1/4 G, 1/4 S, 1/4 H, 1/4 A; and MARC III = 1/4 R, 1/4 P, 1/4 H, 1/4 A). Breed group (parental breed and composite) effects were significant for all traits analyzed. The effects of heterosis were generally important (P less than .05) for all traits in F1, F2, and F3 generations separately and combined in the three composite populations. Generally, the magnitude of heterosis observed at 1 yr of age did not differ from that observed in cows from 2 through greater than or equal to 7 yr old. Adjusting weight to a common condition score resulted in an average reduction of heterosis effects on actual weight by approximately one-fourth. Thus, approximately one-fourth of the effects of heterosis on weight result from heterosis effects on condition score. Generally, retained heterosis in the F3 generation of either 1-yr-old or from 2 through greater than or equal to 7-yr-old cows of the three composite populations did not differ (P greater than .05) from expectation based on retained heterozygosity for the traits analyzed. These results support the hypothesis that heterosis for weight, hip height, and condition score of cows of these age classes is the result of dominance effects of genes. PMID- 1634399 TI - Estimation of direct and maternal heritability and genetic correlation for backfat and growth rate in swine using data from centrally tested Yorkshire boars. AB - The purpose of this study was to estimate components of variance and covariance for backfat and growth rate in swine tested in central test stations in the United States. Data were collected from 26 central boar test stations from 1984 through 1990. The traits analyzed were backfat adjusted to a 104.5-kg basis and ADG adjusted to a 36-kg on-test weight. Records from 7,951 purebred Yorkshire boars were analyzed. Contemporary groups were defined as boars of a breed that were tested and sold as a common group in a test station. Variance components were estimated using a pseudo-expectation method with a multiple-trait, sire maternal grandsire model. Direct heritabilities for backfat and ADG were estimated to be .56 and .24, respectively. Direct maternal effects were significant for both backfat and ADG; they accounted for 11 and 23% of the variance, respectively. The additive genetic correlation between backfat and ADG was approximately zero. Within this population of centrally tested Yorkshire boars, heritability seems to be high for backfat and moderate for ADG, with a significant maternal effect on each trait. PMID- 1634400 TI - A bioeconomic simulation model for a hierarchical swine breeding structure. AB - A stochastic computer model was developed to simulate individual pigs in a hierarchical breeding system. The bioeconomic model was designed as a tool to facilitate the evaluation of selection, culling, and management strategies for a three-tiered breeding structure. Events such as mating, farrowing, and selection occurred weekly. Variables included number of pigs born alive, survival rate from birth to weaning, average daily gain and backfat at 110 kg, number of pigs weaned, feed per gain, days from weaning to 110 kg, age at puberty, and growth rate and weight of sows and service boars. Also included were probabilities of conception, return to estrus by week, survival, involuntary culling, male infertility, and unacceptable conformation. Variables important for selection were determined by breeding value, individual and maternal heterosis, parity, size of birth litter, sex, age of dam, genetic and environmental relationships between variables, and common litter, permanent, and random environmental effects. Variables derived from selection variables were computed by regression using phenotypic relationships between all variables. Also, a random environmental effect was added to predicted performance. Means and variances of variables differed between genetic lines. Production costs included feed, non feed operating, fixed, and replacement stock costs. Income included market animals, culls, and replacements sold to lower tiers. Effects of changes in backfat on market value and sow maintenance feed costs were not modeled. An example is given to illustrate model output. PMID- 1634401 TI - Factors affecting dystocia and early calf mortality in Angus cows and heifers. AB - Calving performance records (965,417) from purebred American Angus herds throughout the United States were used to study dystocia and early calf mortality during the period from 1972 to 1985. A sample of 53 (n = 83,467) herds was used to establish reasonable limits on the expected frequency of dystocia and mortality within and among herds that have good reproductive management programs and to verify the frequencies of scores in all other herds (n = 4,130) reporting calving performance information. The data were analyzed by logistic regression models. Dystocia and perinatal mortality, to a lesser extent, were found to be more frequent in heifers than in cows. The odds of unassisted births vs births with major difficulty were 11.58 times greater in cows than in heifers. In heifers, the odds of an unassisted birth increased with age of dam and decreased with birth weight of calf. At a baseline age of 22 mo the odds of an unassisted birth for calves weighing 30 and 40 kg were .13 and .02 times lower than the odds for calves weighing 20 kg. Alternately, at 29 mo, the odds of an unassisted birth for heifers producing a 20-kg calf were 4.53 times greater than at 22 mo. Survival of calves to 24 h in heifers was primarily affected by birth weight. Heifers producing calves at intermediate weights of 29 kg had higher odds of producing live calves at all ages. Considering all heifers calving at 22 to 29 mo relative to 20-kg calves, the odds for survival to 24 h were 3.83 times greater for 29-kg calves and lower by a factor of .52 for 40-kg calves. PMID- 1634402 TI - Luteinizing hormone, testosterone, and behavioral response of male-oriented rams to estrous ewes and rams. AB - During the breeding season three experiments were conducted to evaluate the LH and testosterone (T) response of rams with male sexual orientation (e.g., male oriented homosexual rams) to female sheep, to male sheep, and to treatment with LHRH. Male-oriented rams were identified through a series of sexual performance and sexual preference tests. Treatments included exposure to estrous females and to males for 15 min (Exp. 1) and exposure to estrous females and to males for 8 h (Exp. 2). Behavioral responses to stimulus animals were recorded. In Exp. 2 homosexual rams mounted males more than females (P less than .02) and exhibited more flehmen (P less than .002) and investigatory sniffs (P less than .01) when exposed to males vs females. Acts of aggression (butting the stimulus animals) did not differ by gender (P greater than .1). Flehmen and butting were positively correlated to LH secretion (P less than .02) of rams exposed to females but not to males. In Exp. 1, LH concentration determined every 15 min for 6 h was not affected (P greater than .05) by the gender of the stimulus animal. In Exp. 2, LH pulse frequency and concentration were similar (P greater than .05) by treatment. Lack of an LH response to sexual activity in homosexual rams was not a result of pituitary or gonadal insensitivity; within 1 h of a single injection of LHRH both LH and T increased (Exp. 3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634403 TI - Performance of Bos indicus-influenced bulls in serving capacity tests and multiple-sire breeding groups. AB - Three experiments were conducted with Santa Gertrudis (SG) or F1 (Gelbvieh x SG or Red Angus x SG) bulls to assess factors that influence copulatory activity and fertility of Bos indicus-influenced genotypes. In Exp. 1, 3-yr-old SG bulls (n = 20) with sexual experience and 20-mo-old virgin SG bulls (n = 34) were allotted in a split-plot design (age, bull within age group, test day, and heifer treatment). Number of mounts (Mt), intromissions (I), and ejaculations (E) were measured 14 d apart during two 30-min serving capacity (SC) tests. Estrus was either induced via progesterone+estradiol cypionate (PE) injections or synchronized with Syncro-Mate B (SMB). There were more (P less than .05) I and E on Test d 2 than on Test d 1. Heifers treated with SMB received more (P less than .001) Mt, I, and E than did heifers treated with PE. Sixteen 20-mo-old bulls from Exp. 1 were allotted to breeding pastures at a bull:heifer ratio of 4:119 +/- 3 for 50 d in Exp. 2. Breeding pasture treatments either included or excluded low SC bulls. Neither pregnancy rate nor least squares mean day of conception differed between treatments. Experiment 3 evaluated copulatory activity with a 2 x 2 factorial arrangement (breed and test day) in 14- to 16-mo-old SG (n = 45) and F1 (n = 16) bulls. The F1 bulls had more Mt, I, and E than did the SG bulls (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634405 TI - Increased postnatal growth rates of offspring after antiestrogen treatment of rat dams during pregnancy. AB - The effects of administration of estradiol antiserum to pregnant rats on birth weight, subsequent growth velocity, carcass composition, and reproductive performance of their offspring were examined. Treated rats were injected i.p. with a potent antiestradiol serum on d 12 of gestation, whereas control rats received a similar injection of normal sheep serum. The pups from the treated rats were 12.2% heavier at birth than those from control rats (P less than .01) and had a greater postnatal growth rate (P less than .05). Chemical analysis of body composition at 56 d of age revealed that there was a tendency for female offspring from treated rats to exhibit carcass characteristics (such as increased percentage of body fat) that were more similar to those of normal male rats than to those of normal female rats. Neither onset of puberty nor reproductive performance was affected by the treatment. These results indicate that treatment of rats during pregnancy with antiestradiol may have potential as a technique for increasing postnatal growth rates. PMID- 1634404 TI - Characterization of somatotropin binding sites in pig skeletal muscle. AB - The present study was conducted to determine whether somatotropin (ST) binding sites are present in crude membrane preparations containing sarcolemma of pig skeletal muscle. Initial characterization experiments indicated that binding of bovine ST (bST) was time- and temperature-dependent and that binding was reversible. At 23 degrees C, binding was maximized between 36 and 48 h, whereas at 4 degrees C binding had not reached a maximum by 96 h. Somatotropin binding was stable between pH 5.5 and 8.5 and increased linearly between 100 and 600 micrograms of membrane protein. Addition of unlabeled bST decreased specific binding of [125I]bST in a dose-dependent manner (ED50: 1 to 1.6 ng/mL). The binding sites for bST were specific because porcine prolactin poorly inhibited bST binding. Scatchard analysis revealed the presence of a single class of binding sites (Ka: 9 to 15 x 10(9)M-1; Bmax: 5 to 6 fmol/mg of protein). In summary, the present report is the first to demonstrate that specific ST receptors are present in pig skeletal muscle. The role that ST plays in directly stimulating muscle growth and(or) muscle synthesis of insulin-like growth factor I (IGF-I) in pST-treated pigs as opposed to changes that occur as the result of an increase in plasma IGF-I concentration remains to be resolved. PMID- 1634406 TI - The effect of live weight gain and live weight loss on body composition of Merino wethers: dissected muscle, fat, and bone. AB - Sheep were slaughtered after live weight gain (LWG) and live weight loss (LWL) to evaluate the effect of different periods of normal and retarded growth on dissected carcass components. Thirty-five Merino wether sheep were allowed ad libitum access to the experimental diet of 80% alfalfa chaff and 20% cereal grain (17.23% CP and 18.10 MJ/kg of GE) to grow from 23.0 to 33.0 kg live weight and then fed to lose 10 kg at 133 g/d. Five animals were slaughtered at live weights of 23.0, 26.3, 29.6, and 33.0 kg during LWG and 29.6, 26.3, and 23.0 kg during LWL. Fleece-free empty BW was similar in both LWG and LWL animals at all common slaughter weights because of the lesser and greater weights of the alimentary tract contents and the fleece, respectively, in the LWL animals. Carcass weight or dissected side weight was greater in LWL animals at each common slaughter weight but significantly so (P less than .05) at the 23.0 kg live weight only. Total side muscle weight was similar in LWG and LWL animals at each common slaughter weight, but the proportion of muscle in the dissected side weight was lower (P less than .05) in LWL animals at 23.0 kg live weight. Total side fat, subcutaneous fat, intermuscular fat, and kidney and channel fat weights were all greater in LWL animals at each common slaughter weight, but significantly so (P less than .05) at the 23.0 kg live weight only. Total side bone weight was higher at both 26.3 kg (P less than .01) and 23.0 kg (P less than .05) in the LWL animals. Weight loss in young sheep mobilized more weight of muscle than fat from the carcass, whereas bone weight was constant. PMID- 1634407 TI - Yield grade and carcass weight effects on the cutability of lamb carcasses fabricated into innovative style subprimals. AB - Lamb carcass (n = 100) were selected from USDA yield grades (YG) 2, 3, and 4 and carcass weight (CW) groups 20.4 to 24.9, 25.0 to 29.5, and 29.6 to 34.0 kg. Lamb carcass were fabricated into semiboneless and boneless subprimals and trimmed to three s.c. fat trim levels: .64, .25, and .00 cm of fat remaining. Innovative subprimals were fabricated and yields were calculated for the subprimals and dissectible components (lean, bone, connective tissue, external fat, and seam fat) from each of the various subprimals. Carcass weight as a main effect in a two-way analysis of variance did not account for a significant amount of the variation in yield among trimmed subprimals or the percentage of the dissectible components, but USDA YG was a significant main effect in determining variation in yield for many of the subprimals or dissectible components. Muscle seaming of shoulders and legs and removal of excessive tails on the loin and rack resulted in a majority of the seam fat being removed from these cuts. Dissection data clearly showed that seam fat is a major component of rack and shoulder cuts and with increasing fatness or higher numerical yield grade there are clearly increased amounts of this depot. Increased trimming of external fat magnifies and draws more attention to the amount of seam fat remaining. Production of heavy, lean lambs would be more useful in an innovative type of program because of the larger-sized muscles. Heavy, fat lambs would not be as useful because of their decreased yields and excess seam fat located in cuts that cannot be muscled seamed because of the loss of retail cut integrity. Seam fat was highly correlated to percentage of kidney and pelvic fat and to external fat thickness and with USDA yield grade but was not strongly correlated to carcass weight. PMID- 1634408 TI - Development of a quantitative quality grading system for mature cow carcasses. AB - Data from 400 cow carcasses were used to develop a new quality grading system. First principal component (FPC) values were determined for shear force (SHR) and palatability attributes of tenderness, connective tissue amount, flavor, and juiciness (JUC). Associated eigenvector load values for those traits were -.48, .54, .51, .46, and .05, respectively, and FPC values ranged from -3.20 to 2.18. Linear regression, using FPC as the independent variate, and SHR and palatability attributes (8-point scale, where 8 was highest) as dependent variates explained a significant amount of variation (P less than .001) in all traits, except JUC, and resulted in R2 values of .71, .89, .80, .66, and .01, respectively. A predictive quality-grade equation was developed using FPC as the dependent variate, and overall maturity (OM), lean color, marbling score (MS), lean firmness, lean texture, fat color (FC), and marbling fineness ([marbling texture + marbling distribution]/2; 8-point scale, where 8 was highest) as independent variates. The resulting best-fit prediction equation (FPC = -.052-[.0031 x OM] + [.0013 x MS] + [.31 x FC]) explained a significant amount (P less than .001) of variation in FPC with R2 = .53, Cp = 15.0, and residual standard deviation = .69. A short-cut equation was developed from this prediction equation. Simple correlations for OM, MS, and FC with FPC were -.56, .39, and .64, respectively. Cow carcasses were assigned to one of three quality grades based on FPC values that corresponded with predetermined acceptability levels for each palatability trait. Newly developed grades were quantitative and less variable than existing grades. Future grades for cow carcasses should include fat color to predict palatability. PMID- 1634409 TI - 15N-leucine and 15N-isoleucine isotope dilution techniques versus the 15N-isotope dilution technique for determining the recovery of endogenous protein and amino acids in digesta collected from the distal ileum in pigs. AB - Twelve gilts, with an average initial BW of 38 kg, were fitted with simple T cannulas at the distal ileum and two catheters in the external jugular veins. The animals were fed twice daily (0800 and 2000) 700 g of one of four diets containing either soybean meal, canola meal, wheat, or barley as the sole protein source. 15N-leucine was infused continuously for 9 d at a rate of 40 mg/kg of BW daily via one of the jugular catheters. Blood samples were taken during feeding. Ileal digesta samples were collected continuously for 24 h on d 7 and 9 of the infusion period. 15N-enrichment excess in leucine and isoleucine in the trichloroacetic acid (TCA)-soluble fraction of blood and in digesta were measured using single-ion monitoring gas chromatography-mass spectrometry. Assuming that the 15N-enrichment excess in leucine and isoleucine in the TCA-soluble fraction of the blood is similar to that in endogenous protein secreted into the digestive tract and that the amino acid composition of endogenous protein is constant, the contribution of endogenous to total protein in ileal digesta was calculated using the 15N-isotope dilution technique for leucine and isoleucine, respectively. These contributions were much smaller for the 15N-leucine than for the 15N isoleucine isotope dilution technique: 7.1 to 11.0 vs 21.8 to 24.9 g of protein/kg of DM intake. The values obtained with the 15N-isoleucine isotope dilution technique were close to those obtained with the 15N-isotope dilution technique as described in a previous publication. PMID- 1634410 TI - Methionine requirement of pigs between 5 and 20 kilograms body weight. AB - Four nursery experiments were conducted using a methionine (Met)-deficient feather meal-corn-soybean meal-dried whey basal diet (20% CP; 3,250 kcal of ME/kg, .11% choline, .19% Met, 1.00% cystine) supplemented with lysine, tryptophan, and histidine to determine the Met requirement of 5- to 10- and 10- to 20-kg pigs. Based on a true Met digestibility value of 81.6% estimated by a pig ileal digestibility assay, the Met-deficient basal diet contained .155% of digestible Met. A preliminary experiment (Exp. 1) indicated that pigs fed the Met deficient basal diet when fortified adequately with Met could produce weight gains similar to those of pigs fed a 20% CP practical corn-soybean meal-dried whey diet. In Exp. 2 and 3, crossbred pigs weighing 5.8 kg initially were fed diets containing graded levels of digestible Met between .195 and .355%. Average daily gain increased quadratically (P less than .05) as the level of Met increased. When the data of Exp. 2 and 3 were examined together, the digestible Met requirement of 5- to 10-kg pigs was estimated to be .255% of the diet. In Exp. 4 and 5, crossbred pigs averaging 10 kg were fed digestible Met concentrations ranging from .155 to .315%. Average daily gain increased quadratically (P less than .05). The digestible Met requirement of 10- to 20-kg pigs was estimated at .255% for maximal weight gain, which was similar to that of 5- to 10-kg pigs. Assuming an 89% digestibility of Met in practical corn-soybean meal diets, the total Met level needed in practice would be .29%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634411 TI - Quantitative influence of lysine and energy intake on yield of milk components in the primiparous sow. AB - A regression approach was used to assess quantitatively the influence of lysine and ME intake during lactation on yield of milk components and to determine whether this influence was mediated through precursor metabolite concentrations in the blood. The influence of lysine and energy intake on sow weight and backfat loss also was analyzed by linear regression. Twenty-three primiparous Landrace x Yorkshire sows were fed one of nine corn-soybean meal diets to achieve a matrix of lysine (15, 30, or 45 g/d) and ME (6.5, 11.5, or 16.5 Mcal/d) intakes. Sow BW and backfat losses were found to be predominantly controlled by ME intake (P less than .02), with no response to lysine intake (P greater than .92). Lysine and ME intake explained a smaller portion of the variability in milk component yield on d 8 (R2 less than .34) than on d 22 (R2 = .64 to .78), evidence that dietary effects of milk production increased as lactation progressed. Lysine and ME intake had an interactive influence (P less than .05) on yield of all milk components except lactose, demonstrating that the amount of lysine required to maximize milk production increased as ME intake increased. Strong relationships between diet and most blood precursor metabolite concentrations (R2 = .5 to .7) were detected on d 22. No obvious relationships between precursor metabolite concentrations and milk component yield (R2 = .05 to .2) were observed. These results describe quantitatively the prominent interactive effects of lysine and ME intake on yield of milk components and demonstrate that these effects are not directly associated with changes in precursor pool concentrations. PMID- 1634412 TI - Interactive effects of dietary levels of tryptophan and protein on voluntary feed intake and growth performance in pigs, in relation to plasma free amino acids and hypothalamic serotonin. AB - The effects of dietary level of tryptophan (TRP) and CP content and composition on voluntary feed intake, growth performance, and carcass characteristics in finishing pigs were studied in two experiments, with an equal number of females and castrated males. In Exp. 1, involving 120 Large White pigs from 44 to 99 kg BW with ad libitum access to feed, six treatments were compared according to a 2 x 3 factorial arrangement: 1) two levels of TRP (.09 and .13%), suboptimal and optimal for growth, respectively, 2) three types of CP supply (a 12.5% CP diet based on corn-soybean meal, and adequately balanced for essential amino acids [EAA] other than TRP; 15.7% CP diet with additional protein from corn gluten meal; 16.2% CP diet with additional nonessential amino acids [NEAA, in the form of L-glutamic acid.HCl and glycine], and the same levels of EAA as in the 12.5% CP diet. In Exp. 2, including four of the six previous factorial combinations (.09 and .13% TRP, 12.3 and 15.8% CP with additional protein), 32 pigs of 50-kg initial BW were used during 21 d, and further observations on meat quality characteristics, plasma free amino acid levels, and serotonin concentrations in the posterior hypothalamus were made. The major observed effects were interactions of different magnitude according to sex between TRP level and the amount and the composition of additional CP. At the suboptimal level of .09% TRP, the increase in protein content severely decreased daily feed intake and growth compared with the .13% level, especially in females. Conversely, the addition of NEAA at both TRP levels had little effect on daily feed intake and growth. Deficiency of TRP exerted a significant increase of pH in adductor femoris and semimembranosus muscles measured 45 min and 24 h postmortem, but only in females. Voluntary feed intake, as affected by dietary TRP and CP levels, was linearly related with concomitant changes in TRP to large neutral amino acids (TRP:LNAA) ratio both in feed and in plasma, which in turn was directly associated to hypothalamic serotonin concentration. It was concluded that an overly low concentration of serotonin in the hypothalamus, especially in females, as a result of TRP:LNAA imbalance, could be involved in the reduction of voluntary feed intake. PMID- 1634413 TI - Secretion of ovine lymphocyte suppressor factor from curetted uterine luminal cells. AB - The secretion of ovine lymphocyte suppressor factor from jugular vein (JV), uterine vein (UV), and curetted hemopoietic uterine luminal (UL) mononuclear cells was evaluated on d 14 of the cycle, following ovariectomy (OVX) and after 14 d of progesterone injections (OVX + P4, 1 mg/kg BW). Mononuclear cells (predominantly lymphocytes) were harvested by Ficoll-Paque and placed into culture (2.5 x 10(6).mL-1.well-1 in RPMI-1640). Cellular supernatants were obtained at 72 h and volumes (5 to 50 microL) were tested for suppression of phytohemagglutinin (PHA [.08 microgram l)-treated peripheral blood lymphocytes (1.0 x 10(5)). In a concurrent experiment, PHA-treated JV, UV, and UL cells (1.0 x 10(5)) were cultured singly and JV cells (1.0 x 10(5)) were also cocultured with each of 1.0 x 10(5), 5.0 x 10(4), and 2.5 x 10(4) UV and UL cells. The incorporation of thymidine into DNA was quantified at 60 h. For the cellular supernatant experiment, thymidine incorporation was affected by reproductive phase (P less than .036), lymphocyte source (P less than .0001), and phase x source (P less than .004). For UL cells, the degree of suppressor activity follows: d 14 greater than OVX greater than OVX+P4 (P less than .05). The UL supernatant from OVX+P4-treated ewes and supernatants of JV and UV cells, irrespective of reproductive phase, lacked suppressor activity. Sephacryl S-200 chromatography revealed that UL supernatant from d-14 ewes contained a greater than or equal to 248,000 molecular weight suppressor macromolecule. For the cellular coculture experiment, thymidine incorporation was affected by reproductive phase (P less than .05) and lymphocyte source (P less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634414 TI - Influence of an agonist of gonadotropin-releasing hormone (buserelin) on estrus synchronization and fertility in beef cows. AB - The objective of this experiment was to determine the effect of sequential treatment with buserelin (a GnRH agonist) and cloprostenol (a prostaglandin F2 alpha analog) on estrous response and fertility in beef cattle with different ovarian conditions. On d 0 (1st d of treatment), the control group (n = 52, 10 heifers and 42 cows) and the GnRH group (n = 48, 10 heifers and 38 cows) received 2 mL of saline or 2 mL of Receptal (8 micrograms of buserelin), respectively. On d 6, all cows that had not exhibited spontaneous estrus were given i.m. 500 micrograms of cloprostenol (PGF). Ultrasonography on d 0 and assays of progesterone in blood on d -11, 0, and 6 were used to identify follicular and luteal status of animals. Cattle were observed for estrus from d 0 to 10. Cows showing estrus were bred artificially 12 h after onset of estrus. Over the 10-d period, the number of cows detected in estrus and pregnancy and conception rates were identical for the two groups. However, between d 0 and 6, the proportion of cows exhibiting estrus was lower (P less than .01) in the GnRH group than in the control group. Between d 6 and 10, the synchronization rate and precision of estrus were greater (P less than .01) in the buserelin-treated group than in the control group. Conception rate and interval from PGF injection to onset of estrus were not different between the two treatment groups. Presence of a large (greater than 10 mm) follicle on d 0 enhanced synchronization rate and precision of estrus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634415 TI - Influence of the embryo on intrauterine migration in sheep. AB - Mechanisms of intrauterine migration were examined in 55 ewes. In the first experiment, corpora lutea were removed from unilaterally ovariectomized ewes on d 4 (d 0 = estrus) and pregnancy was maintained by giving exogenous progesterone. In Exp. 2, the reproductive tract was altered surgically such that embryos initially entered the uterine horn contralateral to the site of ovulation. In Exp. 3, ewes received beads of silastic polydimethylsiloxane that released either cholesterol or estradiol-17 beta in an attempt to mimic embryonic synthesis of estradiol. In the fourth experiment, unilaterally ovariectomized ewes were superovulated and spacing of embryos within the uterus was then examined. In all experiments, ewes were slaughtered on d 15 and recovery of embryos or beads from each uterine horn indicated that migration had occurred. All ewes in Exp. 1 and 2 that had two conceptuses experienced embryonic migration. Beads impregnated with estradiol migrated farther (P less than .01) than cholesterol-containing beads (27.6 +/- 4.3 vs 12.5 +/- 1.6 cm, respectively). In Exp. 4, only one conceptus had migrated into the contralateral horn in all ewes. These results demonstrated that 1) embryonic migration was not affected by local vs systemic exposure to progesterone, 2) embryos migrated into the unoccupied horn, regardless of the initial horn of entry, 3) estradiol may stimulate embryonic migration, and 4) conceptuses were not equally distributed between horns. PMID- 1634416 TI - Effects of pregnant mare's serum gonadotropin treatment on follicular populations and ovulation rates in prepuberal gilts with two morphologically different ovarian types. AB - Two experiments were conducted to determine the effects of pregnant mare's serum gonadotropin (PMSG) on follicular populations and ovulation rates in prepuberal gilts with grape-type (GT) and honeycomb-type (HT) ovaries. The follicular populations were determined at 170 d of age (d 0) and 19 d after PMSG (d 19). In Exp. 1, the mean number of macroscopic follicles of Classes 2 and 3 was greater (P less than .05) in GT (n = 11) than in HT (n = 32) ovaries at d 0, whereas the mean number of those of Class 1 was greater (P less than .05) in HT ovaries. At d 19, no difference was observed between the two ovarian types for any class of follicles. The PMSG-induced ovulation rates were comparable between the two ovarian types (8.3 vs 7.9, GT vs HT, respectively; P greater than .10). In Exp. 2, the microscopic follicular populations were determined on right and left ovaries removed, respectively, on d 0 and 19. At d 0, GT ovaries (n = 5) contained a greater number of Class 5 nonatretic (P less than .01) and atretic (P less than .02) follicles than did HT ovaries (n = 5), whereas at d 19 the mean number was not statistically different between the two ovarian types (P greater than .10). In contrast, gilts with HT ovaries contained a greater (P less than .01) number of Class 4 atretic follicles than gilts with GT ovaries at d 0, whereas at d 19 the mean number was not statistically different between the two ovarian types (P greater than .10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634417 TI - Differences in development of bovine oocytes recovered by aspiration or by mincing. AB - This experiment was performed to clarify relationships between conditions of bovine ovaries and developmental capacity of the follicular oocytes recovered from them and to compare two methods of oocyte collection, aspiration and mincing. Follicular oocytes with surrounding intact, unexpanded cumulus recovered by follicular aspiration or by mincing of tissue from 24 pairs of ovaries were matured and fertilized in vitro. The number of follicular oocytes recovered from pairs of ovaries averaged 32.1 +/- 3.2, but the number recovered varied greatly among the 24 pairs of ovaries (range, 7 to 71). The overall rate of development to the blastocyst stage was 18% (137/771), and the average number of blastocysts produced from a pair of ovaries was 5.7 +/- 1.1 (range, 0 to 17). No relationships were found between the presence of corpora lutea or large follicles and the proportion of oocytes capable of reaching the blastocyst stage in vitro. However, a positive correlation was observed between the number of oocytes obtained from each pair of ovaries and subsequent in vitro development; the correlation was especially high for oocytes obtained by aspiration. These data suggest that the developmental capacity of bovine follicular oocytes after in vitro maturation and fertilization is correlated to the number of antral follicles aspirated from the pair of ovaries. PMID- 1634418 TI - Periodic changes in body composition and in priorities for tissue storage and retrieval in mature beef cows. AB - Sixty mature (4 to 6 yr), nonpregnant, nonlactating beef cows of two breed types, Angus (n = 30) and Simmental (n = 30), were used in a four-period, split-plot study (371 d) to determine the seasonal differences in body composition. Periods were chosen to represent each of the four seasons in one year that ran consecutively from June 14, 1986 to June 20, 1987. Initially, all cows were assigned randomly within breed type to one of four feeding levels based on the cows' estimated maintenance requirement (75, 87.5, 112.5, and 125% of weight maintenance) and were rotated such that all animals were fed at all four feeding levels during the course of the study. Body composition was estimated via isotope dilution initially and at the end of Periods 1 through 3 and via derived regression relationships after Period 4. Body composition differed by breed; Simmental cows had greater (P less than .05) amounts of empty body protein (79.4 vs 55.8 kg, respectively) and less (P less than .05) empty body fat (85.3 vs 93.9 kg, respectively) than the Angus cows. These differences also were apparent when expressed as a percentage of live weight. Season altered components of the empty body. On the average, both breeds mobilized (P less than .05) empty body protein (-3.6 and -5.4 kg for Angus and Simmental cows, respectively) in the summer while simultaneously gaining (P less than .05) empty body fat (15.3 and 30.1 kg for Angus and Simmental cows, respectively). Both breeds subsequently tended to gain empty body protein in the winter and spring.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634420 TI - Use and misuse of multiple comparisons in animal experiments. AB - The objective of many animal experiments is to detect meaningful relationships among treatments and associated responses. Types of comparisons of means include pairwise multiple comparisons, planned orthogonal or nonorthogonal contrasts, and orthogonal polynomials. Some procedures are appropriate only for specific types of treatment designs and specific types of objectives. Pairwise, multiple comparisons are appropriate only for comparing unstructured, qualitative treatments. Planned comparisons partition the overall set of treatment effects into independent or nonindependent subsets, with special application to factorials. Orthogonal polynomial (regression) procedures assess relationships between quantitative treatments and response when a full range of responses or an optimal dose is of interest. Recommendations for appropriate use of each mean comparison procedure are illustrated using data from three Journal of Animal Science articles. Also mentioned are a number of computer graphics packages that provide creative ways to display biological relationships and can be linked to statistical packages for input and to word processors or 35-mm cameras for output. PMID- 1634419 TI - Effects of ruminally degradable and escape protein supplements on steers grazing summer native range. AB - One experiment was conducted during 1989 to determine whether a deficiency exists for either ruminally degradable or escape protein in steers grazing summer native range. Increasing levels of ruminally degradable (.15, .27, and .37 kg/d) and escape protein (.07, .14, and .21 kg/d) replaced a cornstarch and molasses (energy control) supplement. Supplements were isoenergetic and fed individually to steers (.88 kg/d). No response to the degradable protein supplement (P = .15) was observed; however, a linear gain response (P less than .01) was observed in steers fed escape protein in addition to ruminally degradable protein. An in vitro study indicated that more (P less than .01) microbial protein was synthesized from the energy supplement than from the degradable protein; this finding presumably relates to the numerical decrease in weight gains observed for steers fed degradable protein supplements. Analyses of esophageal extrusa samples indicated that CP was relatively constant for the 1989 growing season compared with the 1988 growing season (P less than .05). Escape protein values differed (P less than .01) between years and among months within year. Forages that were apparently grazed in 1989 were never deficient in degradable protein. Additional gain observed from feeding escape protein would indicate that microbial protein synthesis may be insufficient to satisfy the metabolizable protein requirement, which probably limited gains by steers grazing summer native range. PMID- 1634421 TI - Improving social competence. PMID- 1634422 TI - An analysis of the effects of multiple setting events on the social behavior of preschool children with special needs. AB - We examined the effects of four combinations of setting events on the social interactions of 7 preschool children with social delays. In Study 1, the status of the teacher, activity materials, and peer varied across conditions. In Study 2, the status of the teacher and materials varied across conditions. Within the combinations of setting events, we also examined teacher behavior. Teacher presence and absence was varied in both studies. The type and rate of teacher prompting were varied in Study 2. The four combinations of setting events produced different rates of social behavior by the children with social delays. The optimal combination of setting events for promoting peer interaction and reducing teacher-child interaction included teacher absence from the activity, a limited number and form of materials, and children paired with a socially skilled partner. PMID- 1634423 TI - Teaching social skills to students with autism to increase peer interactions in an integrated first-grade classroom. AB - We investigated the use of social skills groups to facilitate increased social interactions for students with autism and their nonhandicapped peers in an integrated first-grade classroom. Social skills groups consisted of training students and peers in initiating, responding, and keeping interactions going; greeting others and conversing on a variety of topics; giving and accepting compliments; taking turns and sharing; asking for help and helping others; and including others in activities. Training occurred during the first 10 min of 20 min play groups, four times per week. Using a multiple baseline across subjects design, results demonstrated increases in the frequency of, time engaged in, and duration of social interactions, as well as the responsivity of students and peers to each other. Results were maintained when students were monitored and given feedback on social performance in play groups and during follow-up. PMID- 1634424 TI - Peer-mediated intervention: attending to, commenting on, and acknowledging the behavior of preschoolers with autism. AB - This study investigated the effects of a peer-mediated intervention on the social interaction of five triads comprised of preschoolers with autism and their typical peers. Strategies thought to facilitate interaction were selected based on analyses of a descriptive data base. Peers were taught to attend to, comment on, and acknowledge the behavior of their classmates with disabilities. These are behaviors preschoolers typically exhibit frequently, but that do not obligate responses to the same extent as questions and requests do. The ABCB reversal designs revealed that improved rates of social interaction during play were clearly associated with the peer intervention for 4 of the 5 children with autism. This intervention offers an alternative peer-intervention package for increasing interaction between children with and without disabilities. PMID- 1634425 TI - A peer-mediated social network intervention to enhance the social integration of persons with moderate and severe disabilities. AB - Increasingly, parents, teachers, and students with disabilities are advocating for interventions that go beyond skill training to provide support for participation in integrated environments and support for friendships. The present research demonstrated a social network intervention for youths with moderate and severe disabilities. Two groups of nondisabled peers were recruited to participate in weekly discussions with an adult integration facilitator to increase opportunities for social interaction for 2 students (1 with autism and 1 who was moderately mentally retarded). The groups met to discuss social interactions that had occurred with the students with disabilities and to talk about strategies to promote greater inclusion of the students into ongoing social interaction. The nondisabled students participated in the design and implementation of social skills interventions during transition times and lunch. The nondisabled students used self-monitoring data sheets to record the quantity and quality of interactions. The frequency of interaction, number of opportunities for interaction, and appropriateness of social interactions were analyzed with a multiple baseline design. Results indicated that the social network intervention was successful in increasing the quantity and quality of interactions and that the network strategy promoted the development of friendships. The results are discussed in terms of the need for additional research showing the relationships between increases in social competence, peer mediated intervention, and the development and support of friendship. PMID- 1634426 TI - Increasing generalized social interactions in psychotic and mentally retarded residents through peer-mediated therapy. AB - This study investigated whether withdrawn adults living in a residential center for psychotic and mentally handicapped persons could serve as peer therapists to increase the social interaction of other withdrawn residents. Two pairs of residents served as participants. Treatments were introduced and evaluated within a multiple baseline with reversal design. After baseline, the peer therapist was instructed to increase the social interactions of a target peer through engagement in social interactions. The results demonstrated that the peer therapist increased the social interactions of target peers. However, these increases did not generalize to other residents until the introduction of a multiple peer therapist condition. The percentage of time the peer therapists interacted with other nontarget residents also increased throughout the study. These results were maintained during a 4-month follow-up condition. PMID- 1634427 TI - Improving social skills and disruptive behavior in children with autism through self-management. AB - The literature suggests that children with autism typically are unresponsive to verbal initiations from others in community settings, and that such unresponsiveness can lead to problematic social interactions and severely disruptive behavior. The present study assessed whether self-management could be used as a technique to produce extended improvements in responsiveness to verbal initiations from others in community, home, and school settings without the presence of a treatment provider. The results showed that children with autism who displayed severe deficits in social skills could learn to self-manage responsivity to others in multiple community settings, and that such improvements were associated with concomitant reductions in disruptive behavior without the need for special intervention. The results are discussed in terms of their significance for improved development of social skills in children with autism. PMID- 1634428 TI - Effects of a videotape feedback package on the peer interactions of children with serious behavioral and emotional challenges. AB - Peer interactions are among the greatest challenges experienced by children who have severe emotional and behavioral problems. This study evaluated an intervention package designed to increase the ratio of these children's desirable to undesirable interactions. The package included three principal components: (a) observation of videotapes following regularly scheduled peer activity sessions; (b) self-evaluation of the children's peer interactions observed on the videotapes; and (c) delayed feedback and reinforcement for desirable peer interactions. Five students from two elementary schools participated. Multiple baseline designs and one reversal were used to evaluate the effects of the intervention package. The results showed that the intervention produced lower levels of undesirable peer interactions and higher ratios of desirable to undesirable interactions for all participants. The results are discussed in regard to their conceptual and applied implications and in terms of specific directions for future research. PMID- 1634430 TI - Generalization and maintenance of preschool children's social skills: a critical review and analysis. AB - This paper summarizes the results of a retrospective review of generalization in the context of social skills research with preschool children. A review of studies from 22 journals (1976 to 1990) that assessed generalization as part of social interaction research provided information concerning the prevalence of studies that have assessed generalization, common practices concerning the production and assessment of generalization, and the overall success of obtaining generalization and maintenance of social behaviors. A comparison of the most and least successful studies, with respect to generalization, revealed some differences concerning the practices employed by studies within each group. Differences differentially related to the production of generalization are discussed and recommendations are provided to guide and support future research efforts. PMID- 1634429 TI - Social validation of component behaviors of following instructions, accepting criticism, and negotiating. AB - This study evaluated whether behaviors often taught as part of social skills training are judged favorably by others. Community judges evaluated the performances of people in various situations requiring one of three social skills: following instructions, accepting criticism, and negotiating to resolve conflicts. These skills were displayed in videotaped scenes by actors with and without mental retardation who acted out roles that had different types of authority relationships, and when different components or clusters of behavior (nonverbal, specific verbal, or general verbal behaviors) were performed well or poorly. The highest ratings by judges were of videotaped scenes that depicted correct use of all behaviors, regardless of which skill was being examined, whether or not the actor had mental retardation, or what the relationship was between the two actors. The lowest ratings were of videotaped scenes that depicted poor performance of all behaviors, and intermediate ratings were obtained when only some of the behaviors were performed poorly. These results, as well as the verbal responses of judges to questions, indicated that the different behaviors commonly used in teaching the skills of following instructions, accepting criticism, and negotiating are relevant to judgment of social performance, and are likely to be reinforced and maintained by social contingencies. PMID- 1634431 TI - On the relationship between self-injurious behavior and self-restraint. AB - Many individuals who exhibit self-injurious behavior (SIB) also exhibit self restraint. Three hypotheses about the determinants of self-restraint have been suggested: (a) Self-restraint is maintained by escape from or avoidance of aversive aspects of SIB, (b) self-restraint and SIB are members of the same functional class, and (c) self-restraint and SIB are functionally independent. This study examined a method by which the relationship between self-restraint and SIB may be investigated using functional analysis. Data were collected on the self-restraint and SIB exhibited by 5 mentally retarded males, while conditions suspected to maintain SIB were manipulated. Results suggested that self restraint, like SIB, may be maintained by idiosyncratic contingencies. Implications of an understanding of self-restraint for the analysis and treatment of SIB are discussed, as are some general possibilities for future research. PMID- 1634432 TI - Teaching children with autism appropriate play in unsupervised environments using a self-management treatment package. AB - The present study used a self-management treatment package to teach 3 children with autism, who exhibited inappropriate play behaviors, to play appropriately in the absence of a treatment provider. After self-management training, generalization and maintenance of the behavior change were assessed. Because of the detrimental effects of self-stimulation (arm flapping, spinning toys, twirling, etc.) on learning, the relationship between self-stimulatory behaviors and appropriate play was measured. Results indicated that the children learned to exhibit appropriate play skills in unsupervised settings, appropriate play skills generalized to new settings, and 2 of the children maintained their gains at 1 month follow-up. In addition, self-stimulatory behaviors decreased as appropriate play increased. Treatment implications of these findings are discussed. PMID- 1634433 TI - Using stimulus equivalence procedures to teach name-face matching to adults with brain injuries. AB - On pretests, 3 men with brain injuries matched dictated names of three therapists to written names, but did not match dictated or written names to photos, produce correct names in response to photos, locate offices given written names, or name therapists on sight. Match-to-sample training established conditional relations between dictated names and photos. Posttests showed the emergence of untrained conditional relations involving photos and written names, indicating development of three classes of equivalent stimuli (each containing a dictated name, photo, and written name). For 1 participant, conditional relations involving photos of office nameplates were also examined, but did not emerge pre- or posttraining. Two participants produced names orally when given photos and sorted written names and faces together after training; the 3rd participant was unavailable for these posttests. After training, 1 participant located and named all three therapists in their offices. PMID- 1634434 TI - Promoting stimulus control with textual prompts and performance feedback for persons with mild disabilities. AB - We assessed whether written task analyses would serve as textual prompts for performing functional tasks by persons with mild disabilities. Several variables that could influence the effectiveness of textual prompts to promote stimulus control were examined across four groups. A consistent finding was that written specific task analyses combined with end-of-trial performance feedback were effective for promoting the acquisition and generalization of several tasks. Performance transferred immediately to natural discriminative stimuli when the written task analyses and feedback were withdrawn for most tasks and participants. For 2 participants, transfer of stimulus control was accomplished by prompt fading, using individualized written task analyses either with or without performance feedback (Group 1). When feedback was not provided, the effectiveness of written specific task analyses was inconsistent across groups. In contrast to the controlling effects of written specific task analyses, written generic task analyses, which specified only major task outcomes, when combined with performance feedback (Group 1) did not control responding. Overall, this research demonstrated the effectiveness of written specific task analyses and performance feedback to promote stimulus control for persons with mild disabilities. PMID- 1634435 TI - A comparison of two approaches for identifying reinforcers for persons with severe and profound disabilities. AB - The development of effective training programs for persons with profound mental retardation remains one of the greatest challenges for behavior analysts working in the field of developmental disabilities. One significant advancement for this population has been the reinforcer assessment procedure developed by Pace, Ivancic, Edwards, Iwata, and Page (1985), which involves repeatedly presenting a variety of stimuli to the client and then measuring approach behaviors to differentiate preferred from nonpreferred stimuli. One potential limitation of this procedure is that some clients consistently approach most or all of the stimuli on each presentation, making it difficult to differentiate among these stimuli. In this study, we used a concurrent operants paradigm to compare the Pace et al. (1985) procedure with a modified procedure wherein clients were presented with two stimuli simultaneously and were given access only to the first stimulus approached. The results revealed that this forced-choice stimulus preference assessment resulted in greater differentiation among stimuli and better predicted which stimuli would result in higher levels of responding when presented contingently in a concurrent operants paradigm. PMID- 1634436 TI - Fish cell lines as targets for bacterial cytotoxins. PMID- 1634437 TI - Heme-containing compounds replace chick embryo extract and enhance differentiation in avian muscle cell culture. PMID- 1634438 TI - Estrogen-dependent expression of the chicken very low density apolipoprotein II gene in serum-free cultures of LMH cells. AB - The estrogen-responsive Leghorn strain M chicken hepatoma (LMH) cell line provides a model system for studying the estrogen-dependent, liver-specific expression of avian genes. Serum-free culture conditions have been established that allow expression of apolipoprotein B, very low density apolipoprotein II (apoVLDLII), serum albumin, and transferrin at levels detectable by Northern blot analysis. Regulation of apoVLDLII mRNA by estrogen occurred in an appropriate time- and dose-dependent manner in serum-free cultures of the LMH cells. The expression of apoVLDLII mRNA in serum-free culture was at least 100-fold higher than that expressed in cultures containing 10% serum. The level of estrogen receptors in LMH cells cultured with 10% serum was approximately 2000 receptors per cell, and in serum-free culture approximately 1000 receptors per cell. When these cells were transfected with estrogen receptor DNA and cultured in serum free medium, apoVLDLII mRNA was decreased relative to that expressed in cells transfected with a control plasmid. These results indicate that when the LMH cells are cultured without serum, estrogen receptors are not the limiting factor for the expression of the apoVLDLII gene. PMID- 1634439 TI - Development and characterization of breast carcinoma cell lines as in vitro and in vivo models for breast cancer diagnosis and therapy. AB - To establish a model system for preclinical radioimmunotherapy studies, attempts were made to graft 16 different human breast carcinoma cell lines into BALB/c nu/nu(nude) mice. Nine produced serially transplantable tumors growing at a variable rate, whereas seven failed to do so. Conversely, three new cell lines were established in monolayer culture from transplantable human breast tumors in nude mice. Twelve selected tumors and their corresponding cell lines were characterized for DNA ploidy, % S-phase, and breast epithelial mucin expression by immunohistochemistry and flow cytometry. A wide diversity of these cellular characteristics were found in that each tumor was unique and distinct from the others. DNA ploidy differed among the tumors but was not affected by switching between in vitro to in vivo growth. Some tumors expressed similar levels of the breast mucin both in vitro and in vivo, whereas most expressed lower levels as transplantable tumors. There was a good correlation between immunohistochemical and flow cytometric determination of surface and cytoplasmic mucin expression, and with both techniques estrogen and progesterone receptor positive tumors had significantly higher levels of mucin expression than receptor negative tumors. These 12 transplantable breast tumors, with their corresponding cell lines, provide an excellent model system for testing radioimmunotherapy and other therapeutic reagents because they exhibit diverse phenotypic characteristics that represented a mini-population of breast cancer patients' tumors, allowing assessment of the effect of therapy when confronted with different breast tumors' genotype and phenotype. PMID- 1634440 TI - Role of endothelial cells in the proliferative response of cultured pulmonary vascular smooth muscle cells to reduced oxygen tension. AB - The development of pulmonary hypertension in a wide variety of human disease states and experimental animal models characterized by chronic alveolar hypoxia is mediated by two pathologic vascular processes, a) vasoconstriction and b) vasoconstruction (structural remodeling). The anatomic changes seen within the pulmonary circulation include a) increased deposition of collagen and elastin in the adventitial layer and b) aberrant pulmonary vascular smooth muscle cell proliferation and maturation in the medial segments. Despite the demonstrated ability of pharmacologic manipulation in the experimental animal to ameliorate both the structural and hemodynamic changes, the actual etiologic mechanisms are only beginning to be explored. Using the cell culture technique of co cultivation, we have investigated the potential role of bovine pulmonary arterial endothelial cell-derived factors in mediating abnormal bovine smooth muscle cell growth under conditions of reduced oxygen tension. We have demonstrated that these cultured endothelial cells exposed in vitro to reduced levels of atmospheric oxygen concentrations of 5.0% and 2.5% O2 for durations of 24 to 72 h produce and secrete soluble growth factor(s) which stimulate smooth muscle cell proliferation when compared to cells maintained under standard tissue culture oxygen conditions of 95% room air. This growth-stimulatory effect required the concomitant presence of serum factors (0.5% fetal bovine serum), was inhibited by heparin, was distinct from platelet-derived growth factor, and seemed to have a molecular weight greater than 14,000 Da. We conclude that reduced levels of oxygen tension in vitro can selectively induce pulmonary arterial endothelial cells to release mitogen(s) which can stimulate vascular smooth muscle replication. Furthermore, we speculate that this in vitro finding may be of importance as an etiologic mechanism to explain the accelerated smooth muscle cell growth characteristic of hypoxic pulmonary arteriopathy. PMID- 1634441 TI - 5,8,11,14-eicosatetraynoic acid-induced destruction of mitochondria in human prostate cells (PC-3). AB - Culturing human prostate PC-3 cells for 4, 24, or 72 h in the presence of 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of arachidonic acid metabolism and cholesterol biosynthesis, markedly altered the morphology and reduced the number of mitochondria in the treated cells. Using quantitative electron microscopic morphometry, we documented changes in the number, form, area, matrix density, and integrity of the cristae and limiting membranes of mitochondria in cells cultured with ETYA. The inhibition of cholesterol synthesis or the substitution of ETYA for polyunsaturated fatty acids in the inner membrane may participate in the disruption of the mitochondria, which resembles the morphologic sequelae of oxidative stress. If sufficiently extensive, these changes could contribute to the inhibition of cellular proliferation by ETYA. PMID- 1634442 TI - Serum and insulin inhibit cell death induced by cycloheximide in the human breast cancer cell line MCF-7. AB - Continuous exposure of cells to cycloheximide (CHM) terminates in cell death. This may result from CHM's inhibition of protein synthesis. In the present study we investigated the effect of serum and insulin on cell death induced by CHM in the human breast cancer cell line MCF-7, and correlated this effect to the inhibition of protein synthesis. Cell death was evaluated by measuring either dead cells by the trypan blue dye exclusion test or by the release of lactic dehydrogenase into the culture medium. CHM (0.1 to 50 micrograms/ml) was shown to induce cell death in a time- and concentration-dependent manner. Including either fetal bovine serum or insulin in the culture medium inhibited this cell death in a concentration-dependent manner. Protein synthesis as measured by [3H]leucine incorporation was inhibited by the increasing concentration of CHM. However, fetal bovine serum and insulin did not alter the protein synthesis inhibition rate induced by CHM. These results indicate that inhibition of protein synthesis is not enough for cell death to proceed. Insulin or factors present in serum may stabilize some crucial cell proteins (key enzymes, cytoskeletal or membrane components) which are vital for cell life. PMID- 1634443 TI - Transforming growth factor-beta: its effect on phenotype reexpression by dedifferentiated chondrocytes in the presence and absence of osteogenin. AB - The single and combined actions of transforming growth factor (TGF)-beta and osteogenin were evaluated with regard to induction of colony formation and reexpression of the differentiated phenotype by dedifferentiated rabbit articular chondrocytes in soft agarose under serum-free conditions. TGF-beta alone did not promote colony formation and induced accumulation of proteoglycans and type II collagen at significantly lower levels than those induced by osteogenin. Although synergism between these two growth factors occurred with respect to the induction of colony formation, their joint action on reexpression of the differentiated phenotype was additive. Complex interactions between the two growth factors may explain the latter phenomenon. PMID- 1634444 TI - Thymidine kinase-deficient mutants of Aedes albopictus mosquito cells. AB - Aedes albopictus mosquito cells resistant to the thymidine analog 5 bromodeoxyuridine (BrdU) were obtained using a single-step selection procedure. The resistant cells were characterized with respect to growth in the presence of BrdU, incorporation of [3H]uridine and [3H]thymidine, and thymidine kinase activity in crude extracts. The LC50 for TK-6 cells was 95 micrograms BrdU/ml, and for TK-8 cells was 45 micrograms/ml. Both clones incorporated [3H]uridine at levels corresponding to those in wild-type cells. TK-6 and TK-8 cells did not incorporate [3H]thymidine into acid-precipitable material, nor did they contain measurable thymidine kinase activity. Thymidine kinase activity in crude extracts from wild-type cells had a Km of 2 microM and a Vmax of 10 pmol.min-1.mg-1 protein. PMID- 1634445 TI - Cryopreservative effect of leupeptin on early human bone marrow progenitors. AB - Leupeptin, a thiol- and serine-proteinase inhibitor of low molecular weight, quickly enters viable cells. This property has been used to protect cells during thawing against intracellular proteolytic activities released by injured lysosomes. The bone marrow nucleated cells were frozen without rate-controlled freezing devices. Concentrations ranging from 0.1 to 1 microM of leupeptin allow to recover 87% of the most immature multipotent bone marrow progenitors which can develop in vitro into large multilineage colonies, instead of 58% recovery without leupeptin. The protective effect of leupeptin is particularly useful to freeze cells difficult to cryopreserve or when freezing-control equipment are not available. PMID- 1634446 TI - Exercise-induced asthma in the Olympic athlete. PMID- 1634447 TI - Importance of physical exercise training in asthmatics [see comment]. PMID- 1634448 TI - Plasma theophylline concentrations and airway function in asthmatic children receiving standard and modified RTC therapy. AB - The effects of three different dosage schedules for sustained-release theophylline (Theolong) were investigated in children with asthma. With regimen II (unequal doses at 0800 h and 2000 h), the maximum plasma theophylline concentration following the evening dose was significantly higher than that following the morning dose, and also was larger than that following the evening dose with regimen I (equal doses at 0800 and 2000 h). With regimen III (equal doses at 0600 h and 2100 h), the mean theophylline concentration-time curve showed a single large peak at 1100 h, whereas with regimen I, there were two peaks at 2300 and at 1400 h. Knowledge that a change of the dosage schedule can affect the pharmacokinetics of theophylline in this way should aid physicians in its safe and effective use. PMID- 1634449 TI - Effect of ibudilast: a novel antiasthmatic agent, on airway hypersensitivity in bronchial asthma. AB - Ibudilast, a unique agent with vasodilating and antiallergic actions, was studied in 13 asthmatics for its effect on airway hypersensitivity to histamine inhalation. The PC20 values improved significantly from 355.6 to 620.5 micrograms/ml at 3 months and further to 731.4 micrograms/ml at 6 months following the initial treatment with ibudilast (20 mg twice daily orally). In addition, the severity of the attacks decreased significantly. Improvements in the PC20 and asthmatic symptoms also were observed in the disodium chromoglycate group, but these were equal to or lesser than those in the ibudilast group. No improvement was observed in the untreated control group. These results suggest that ibudilast would be an effective agent for improving nonspecific airway hypersensitivity in asthmatics. PMID- 1634450 TI - Asthma and the use of CNS depressants: gender differences. AB - A retrospective 5-year random sample of 196 charts of patients with asthma was obtained from two hospital-based outpatient clinics. The chart reviews showed that age- and severity-matched males and females with asthma were prescribed antihistamines in similar proportions; however, 16.8% of the females were prescribed a tranquilizer or sedative compared with 8.5% of the males. The females (8.7%) also were prescribed a combination of these drugs, or two tranquilizers; none of the males were prescribed more than one CNS depressant. Results showed that, in this study, females were prescribed CNS depressants three times as often as males. PMID- 1634451 TI - Passive smoking among children with chronic respiratory disease. AB - The purpose of this study was to determine the prevalence and source of passive smoke exposure among children with chronic respiratory diseases and compare these to both a well child and nonrespiratory chronic illness child population. Rates and source of passive smoke exposure were compared among four child groups: asthma, cystic fibrosis, rheumatoid arthritis, and well children using a questionnaire mailed to the parents of the selected children. Twenty percent of respondents reported current smoking with a significantly higher rate among the cystic fibrosis and rheumatoid arthritis groups. One-third of all children surveyed were exposed to passive smoke at home and/or day care on a daily basis. Over 80% of the asthma and cystic fibrosis respondents reported a change in smoking behavior (i.e., smoking outside the home or smoking fewer cigarettes) after the diagnosis of their child's illness as compared with only 40% of the nonrespiratory groups. Health care providers need to inquire about potential sources of passive smoke exposure in their patients, particularly children with chronic respiratory disease. PMID- 1634452 TI - Evaluation of a once-a-day theophylline preparation in asthmatic children. AB - We conducted a study to evaluate the serum theophylline concentrations and dose interval of Theolan preparation in asthmatic children. A series of serum theophylline levels were measured both in 10 asthmatic children taking Theolan once a day and 9 children twice a day. In the once-a-day group, the peak serum theophylline level was greater than 20 micrograms/ml; whereas, in the twice-a-day group, it was mostly between 10 and 20 micrograms/ml. The difference of the peak to-trough was more fluctuant in the once-a-day group than in the twice-a-day group. These results suggest that Theolan given once a day in the evening can be useful in the management of nocturnal asthma; however, it was difficult for once a-day administration of Theolan to sustain rigid therapeutic serum theophylline levels. Because of rapid metabolism in children, they may require a more frequent interval than once-a-day dosing to suppress the symptoms of chronic asthma. PMID- 1634453 TI - Acquired coagulation factor inhibitors. PMID- 1634454 TI - Erythrocytic glucose-6-phosphate dehydrogenase deficiency in the Bania community of Punjab. AB - Five hundred members belonging to the Bania community of Punjab were screened for erythrocytic glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. The incidence of enzyme deficiency in males was 2.84 per cent and in females 2.75 per cent, with an overall incidence of 2.80 per cent. No correlation between age and G-6-PD deficiency was found. The mean values for haemoglobin and haematocrit did not differ significantly in the normal and deficient subjects. Study of the deficiency pattern amongst family members of the enzyme deficient subjects confirmed the X-linked inheritance of G-6-PD deficiency. PMID- 1634455 TI - Evaluation of purified protein derivative in the laboratory diagnosis of tuberculous meningitis. AB - An enzyme-linked immunosorbent assay (ELISA) was standardised for the quantitation of IgG antibody in cerebrospinal fluid (CSF) specimens of patients with tuberculous meningitis (TBM). Purified protein derivative (PPD1) from H37Ra M tuberculosis was used as the antigen in the assay. The sensitivity of the ELISA with this antigen was evaluated in the CSF of 10 culture positive and 40 culture negative patients with TBM. The specificity of the assay was evaluated in the CSF of 50 patients with non-tuberculous neurological diseases (control group). The results obtained with this antigen were compared with commercially available tuberculin purified protein derivative (PPD2) and BCG antigens. PPD2 gave false negative results (50%) in culture positive patients with TBM, and BCG antigen gave false positive results in 32% of non-tuberculous subjects. PPD1 gave a sensitivity of 60% in culture negative patients with TBM and no false positive reactions in the non-tuberculous group. PPD1 antigen, in contrast to other mycobacterial antigens, can be very easily prepared in any routine laboratory, and this antigen is recommended for use as an aid in the laboratory diagnosis of TBM, particularly in culture negative patients with TBM. PMID- 1634456 TI - Infections in acute myeloid leukemia. Study of 184 febrile episodes. AB - We analysed the case records of 75 patients with acute myeloid leukaemia treated at our institute from January 1984 to December 1988 to see the pattern and severity of infections and their relationship with granulocytopenia. A total of 184 febrile episodes (mean 2.45) were recorded; 153 (83.15%) were associated with granulocytopenia while 31 (16.84%) were without granulocytopenia. Among granulocytopenic patients, infections could be documented microbiologically in 58.2% and clinically in 30.0% of episodes. In the remaining 41.8% of episodes, no clinical, radiological or microbiological evidence could be found out. The various sites of infection were: septicaemia 21 (13.72%), disseminated fungal infections 4 (2.6%), upper respiratory tract 21 (13.7%), chest 58 (37.9%), gastrointestinal tract 8 (5.2%), genitourinary (7.2%), soft tissues 5 (3.2%) and skin cellulitis 7 (4.6%). Microbiologically, gram negative organisms (Klebsiella pneumoniae, E coli, Pseudomonas aeruginosa) were most common, followed by gram positive (Streptococcal faecalis, Staphylococcus aureus, Staph albus, Staph epidermidis). Four patients had disseminated fungal infection: candida 2, aspergillus *1, mucormycosis *1. Among non neutropenic febrile episodes, the sites infected were: septicemia 2 (6.4%), chest 9(29.0%), upper respiratory tract 1 (3.2%), gastrointestinal 1 (3.2%), soft tissue 1 (3.2%), drug fever 3 (9.6%) and fever of unknown origin 14 (45.2%). PMID- 1634457 TI - Extrathoracic Castleman's disease. AB - Castleman's disease is an uncommon clinical entity. We report two cases of this disease with a brief review of literature. Both of them had extrathoracic disease which is relatively infrequent. One of them presented with localized hyaline vascular type of the disease and the other with the multicentric plasmacytic variety. The patient with the latter form of Castleman's disease had sclerodactyly, which has not been reported earlier in association with this disease. PMID- 1634458 TI - Hepatic changes during short-term haemodialysis. AB - Twenty five patients with end stage renal disease were studied to find out the biochemical and hepatic morphological changes during short term haemodialysis. Asymptomatic hepatomegaly was seen in 32% of cases, transaminase elevation in 28% and positive Australia antigen in 12% of cases. Histopathological changes were observed in all the 12 patients in whom liver biopsy was done. Ten patients (82%) exhibited multiple abnormalities. The commonest findings were fatty change (8 patients); hepatic congestion, focal necrosis, Kupffer cell hyperplasia (6 patients each); and portal triaditis (5 patients). PMID- 1634459 TI - Cutaneous metastasis in lung cancer. PMID- 1634460 TI - Basic concepts of clinical pharmacokinetics. AB - Clinical pharmacology is now a well established discipline. Unlike the yester years when dosage schedules were determined by trial and error, in the present day selection of dose, dosage interval and route of administration are based on pharmacokinetic and pharmacodynamic principles. The primary utility of pharmacokinetics is to study the process of absorption, distribution, metabolism and elimination of drugs, fundamental for drug action. Individuals show a wide variation in kinetic parameters due to internal and external factors. Sometimes change in one variable may be compensated by change in another variable so that dose need not be altered e.g. metabolism of some drugs is increased in thyrotoxicosis but due to increased protein binding overall dose adjustment may not be required. On the other hand sometimes variations in these parameters can markedly affect the plasma concentrations of and the pharmacological response to drugs e.g. anticonvulsant treatment in oral contraceptive users, phenylbutazone addition in warfarin therapy. Drug concentrations can be measured in plasma, urine or saliva. Equipped with this knowledge the modern physician will be able to make a wiser use of drugs under altered physiological conditions like pregnancy, lactation, infancy, old age and pathological states like renal and liver failure and shock. PMID- 1634461 TI - Infections in acute leukaemia. PMID- 1634462 TI - Aortic saddle embolus. PMID- 1634464 TI - Factor VII inhibitor. AB - Acquired inhibitors of blood coagulation factors occur spontaneously or secondarily to various diseases or drug administration. A clinically significant factor VII inhibitor is very rare. We report a patient developing factor VII inhibitor possibly as a reaction to penicillin administration; it gave rise to fatal haemorrhage. PMID- 1634463 TI - Treatment of anaemia of progressive renal failure with recombinant human erythropoietin. A preliminary report. AB - We report response in anaemia and wellbeing of a lady with chronic renal disease treated with recombinant human erythropoietin 5000 units thrice weekly. Without any blood transfusions, the patient's haematocrit improved (20% to 35%) and a subjective improvement in wellbeing and appetite was noted. This drug seems to be a breakthrough in the management of anaemia of chronic renal diseases, including end stage renal disease, avoiding the risks of repeated blood transfusions. PMID- 1634465 TI - Herpes zoster oticus associated with facial, auditory and trigeminal involvement. AB - We report a case of herpes zoster oticus with involvement of the mandibular division of the trigeminal nerve and loss of taste sensation in the anterior two third of the tongue. Infranuclear facial palsy and sensorineural deafness were also present. PMID- 1634466 TI - Cutaneous anthrax--a report of ten cases. AB - The clinical features of ten cases of cutaneous anthrax are reported. Six males and four females were affected. Their ages ranged from one and a half year to sixty years. The average incubation period was 8 days. Fever and headache were common systemic manifestations. Pruritus and ulcer with formation of black eschar were typical features. The patients were treated with penicillins and chloramphenicol. There was no mortality. Possible human-to-human spread in a patient is discussed. PMID- 1634467 TI - Thin membrane nephropathy. PMID- 1634468 TI - Granulocytic sarcoma of the paranasal sinus. AB - We describe a young adult male with granulocytic sarcoma of the paranasal sinuses and nose with acute non-lymphoblastic leukaemia. Complete remission was achieved after systemic chemotherapy and localised radiation therapy. The patient died four months later due to disseminated aspergillosis. PMID- 1634469 TI - Right ventricular mural infective endocarditis in a patient with burns. AB - An individual who had sustained 43% burns and then developed blood culture negative right ventricular infective endocarditis and right basal segmental pulmonary infarction is reported. Echocardiography detected vegetations in the mid right ventricle. The patient had a central venous catheter in situ during the initial stage of management of burns. Following therapy, he recovered uneventfully from his extremely toxic and febrile state. PMID- 1634470 TI - Progressive dystonia with marked diurnal fluctuation. AB - Two cases of dopa-responsive dystonia with marked diurnal fluctuations are reported. Of these, one was a 26 year old female who had progressive dystonia of more than 20 years' duration with classical diurnal fluctuations exacerbated by exercise and relieved with sleep; she also had significant worsening during menstruation and the later half of her pregnancy, resulting in a stillbirth. She responded remarkably to low doses of L-dopa. PMID- 1634471 TI - The puzzle which is pyrexia of undetermined origin. PMID- 1634472 TI - Miosis with haloperidol. PMID- 1634473 TI - Erythropoietin: a therapeutic tool. PMID- 1634474 TI - Male infertility. PMID- 1634475 TI - Aetiologic factors in male infertility: clinical, microbiological and hormonal evaluation. AB - Seventy two infertile men were studied. History of small pox and mumps infection was noted in 4 and 3 patients respectively. Seven patients had varicocele (9.2%), and small atrophic testes were found in 9 (12.5%). Azoospermia was reported in 41 (58.3%) and oligospermia in 17 (23.6%), and 14 patients (19.4%) had normal sperm counts. Mycoplasma were grown from urethral swabs in 25 (35%) patients. Mean LH and FSH were elevated in azoospermics (p less than 0.001), E2-17B in oligospermics (p less than 0.001) and FSH in normospermic (p less than 0.01) patients. Hypergonadotropism suggestive of primary testicular failure was recorded in 43 (59.7%) patients. Hypogonadotropism was noted in 3 (4%) and hyperprolactinemia due to pituitary microadenoma induced infertility in only one patient. No aetiology could be determined in 11 (16%) patients. PMID- 1634476 TI - Platelet aggregation in migraine. AB - This study was conducted on forty male patients aged 17-35 years, suffering from migraine. Platelet aggregation was evaluated in them twice, once in the aura and headache phase of migraine and the other during the period in which patient was asymptomatic. We observed significant increase in platelet aggregation during the aura and headache phase of the migrainous attack in comparison to the headache free interval. Platelet hyperaggregability may be an important factor in the pathogenesis of migraine. PMID- 1634477 TI - Thyroid morphometry and intrathyroidal 131-I iodine transit kinetics in Kashmiri population. AB - Morphometric--kinetic parameters of the thyroid gland in the Kashmiri population, which is geographically, environmentally, socioculturally, anthropologically and ethnically different from that of the main country (Indian republic), have been analysed. Morphometrically, the gland in this population has been found to be significantly larger (p less than 0.001), while kinetically, the A max which is the ordinate-extrapolate of the best-fit RAIU(t) curve, has been found to be significantly lower (p less than 0.01). The majority of other structural and functional parameters were similar to those of the north Indian population. PMID- 1634478 TI - Adenosine deaminase in pleural effusions. AB - The serum adenosine deaminase (ADA) level was estimated in 30 patients with pleural effusion and 18 healthy controls and was found to be significantly elevated in the former (P less than 0.001). The pleural fluid ADA level in tubercular pleural effusion was always above 50 U/L and was significantly higher than in nontubercular effusions (P less than 0.001). Pleural fluid ADA to serum ADA ratio was not helpful in the aetiologic diagnosis of pleural effusions. Thus, estimation of pleural fluid ADA is a safe, simple, reliable and non-invasive test in distinguishing tubercular and non-tubercular pleural effusions. PMID- 1634480 TI - A comparison of the clinical efficacy of ranitidine and sucralfate in reflux oesophagitis. AB - Forty patients with endoscopically proved reflux oesophagitis were treated in a randomised study. Treatment was given for six weeks and consisted of either 1 g sucralfate four times a day or 150 mg ranitidine tablet twice daily. Twenty patients received each drug. Clinical evaluation was done weekly and endoscopic evaluation after six weeks. Eight patients on ranitidine and ten patients on sucralfate became asymptomatic at six weeks. Ten patients on ranitidine and twelve patients on sucralfate were endoscopically healed. There was no difference in the effect of ranitidine and sucralfate treatment (p greater than 0.05). Overall tolerance and compliance with the two forms of treatment were good. Though ranitidine has a more convenient dose schedule and is more cost-effective, sucralfate needs further clinical evaluation. PMID- 1634479 TI - Alpha-interferon in hairy cell leukemia: an initial Indian experience. AB - In the last decade, 14 patients were diagnosed as having hairy cell leukemia (HCL) at our hospital; five of these were treated with the biological response modifier, recombinant alpha-interferon (IFN), as their initial treatment. Four of these cases showed a complete remission of the disease while one had a good partial response after a few months of therapy. One case is in unmaintained remission while one has relapsed with a just palpable spleen on stopping the drug; two are still on intermittent IFN therapy while one has been lost to follow up. Fever and skin rash were the most common side effects observed but did not warrant reduction of dose or stoppage of treatment. We conclude that IFN is highly effective and well tolerated as initial treatment of HCL in a country like India. Splenectomy will continue to be the first line therapy in the majority of cases but, in certain selected situations, IFN can be an extremely useful alternative. PMID- 1634481 TI - Acute Campylobacter jejuni enteritis in 385 hospitalised patients. AB - Twenty healthy controls and 385 adult patients suffering from acute enteritis or gastroenteritis were enrolled for the study of Campylobacter Jejuni infection over a period of 2 years. Thirty five stool samples showed C jejuni on stool culture. The isolation rates were at peak in the monsoon season and from watery and bloody stool specimens. Pure C jejuni culture was obtained in 18 of 35 samples; the other 17 samples showed polymicrobial infection or infestation. Nine of 35 patients were treated with erythromycin 1 g in divided doses for 7 days. Repeat stool cultures did not grow C jejuni. There was no resistance to erythromycin therapy. C jejuni are fastidious organisms and require special medium and microaerophilic environment for culture. PMID- 1634482 TI - Cytokines in rheumatic diseases. PMID- 1634483 TI - Chloramphenicol and ciprofloxacin in enteric fever--cost-effectiveness. AB - Clinical decision analysis is a technique which is used to deal with uncertainities in clinical medicine. We used this technique to compare the cost effectiveness of chloramphenicol and ciprofloxacin in the treatment of enteric fever. The study shows that the most economical alternative can be predicted if the cost of hospital stay and the sensitivity of the organism to chloramphenicol are known. Thus if the hospital costs are Rs 50/- per day, chloramphenicol will be the drug of choice if more than 52% of the organisms are sensitive to the drug. At lower levels of sensitivity to chloramphenicol, ciprofloxacin will be the drug of choice. PMID- 1634484 TI - Influence of prior information of drug toxicity on patient compliance. AB - Sixty patients with pulmonary tuberculosis, who had not received any chemotherapy in the past, were divided into two groups. All the patients were put on isoniazid, rifampicin and pyrazinamide for 8 weeks followed by isoniazid and rifampicin for another 18 weeks. Group A patients were informed of the likely occurrence of anorexia and/or vomiting but Group B patients were not. Routine and default retrieval home visits were given to ensure maximal drug compliance. Drug toxicity related early defaults were significantly less common in Group A patients (1 of 30) as compared to Group B (6 of 30). PMID- 1634485 TI - Acupuncture--a critical evaluation. AB - Acupuncture is a traditional form of Chinese medicine which has been in practice for over 3000 years. It was not accepted in the West mainly due to cultural barriers. However, research during the last decade has established the physiological basis of acupuncture. Although it is mainly used for chronic musculoskeletal pain in the West, it also has a place in the treatment of various non-painful disorders like bronchial asthma, alcohol and nicotine addiction and functional gastrointestinal disorders. Controlled trials published in the literature have many methodological flaws, and these can be rectified by standardisation of acupuncture technique. Since traditional Chinese medicine and Western medicine differ in their concepts of anatomy, physiology and systems of diagnosis, it is not possible to reconcile them into a common language. However, it is possible for them to co-exist. PMID- 1634486 TI - Diarrhoeal diseases in Calcutta. PMID- 1634487 TI - Spontaneous left ventricle cavity thrombus in a patient of systemic lupus erythematosus. AB - A 32 year old female with systemic lupus erythematosus having circulating lupus anticoagulant developed a thrombus in the left ventricle cavity, an unusual site. She responded to standard anticoagulant regime. PMID- 1634488 TI - Giant epithelioid leiomyoblastoma of the stomach--a diagnostic dilemma. AB - Epithelioid leiomyoblastoma (ELB) of the stomach is an uncommon slow growing smooth muscle tumour, attaining enormous size and presenting with bizzare symptoms. We report one such case which posed a diagnostic problem to both the clinician and the radiologist; the condition was diagnosed after laparotomy and histological examination. PMID- 1634489 TI - Visceral larva migrans in an adult. AB - Visceral larva migrans is rare in adults. An adult male in whom the diagnosis was made by suggestive clinical features and muscle biopsy and who responded to thiabendazole is described. PMID- 1634490 TI - Primary amoebic lung abscess. PMID- 1634491 TI - Herpes zoster associated encephalitis. AB - Herpes zoster associated encephalitis is a very rare complication of herpes zoster. We are reporting a young healthy man who developed this complication along with the usual cutaneous presentation of herpes zoster. He was successfully treated with acyclovir. PMID- 1634492 TI - Congenital hemihypertrophy with mental retardation. PMID- 1634493 TI - Atropine infusion in organophosphorus poisoning. PMID- 1634494 TI - Ataxia telangiectasia. PMID- 1634495 TI - Renal involvement in leprosy. PMID- 1634496 TI - Chloramphenicol-resistant enteric fever. PMID- 1634497 TI - Intravenous magnesium in acute myocardial infarction. PMID- 1634498 TI - Thrombolysis in myocardial infarction--for whom? PMID- 1634499 TI - Viral encephalitis--overdiagnosed, undertreated. PMID- 1634500 TI - Genesis of thalassaemia intermedia. PMID- 1634501 TI - Pigmentation following cyclophosphamide therapy. PMID- 1634502 TI - Global headache in angina pectoris. PMID- 1634503 TI - Alpha: the Cinderella subunit of RNA polymerase. PMID- 1634504 TI - Fructose transporter in human spermatozoa and small intestine is GLUT5. AB - We recently reported that the glucose transporter isoform, GLUT5, is expressed on the brush border membrane of human small intestinal enterocytes (Davidson, N. O., Hausman, A. M. L., Ifkovits, C. A., Buse, J. B., Gould, G. W., Burant, C. F., and Bell, G. I. (1992) Am. J. Physiol. 262, C795-C800). To define its role in sugar transport, human GLUT5 was expressed in Xenopus oocytes and its substrate specificity and kinetic properties determined. GLUT5 exhibits selectivity for fructose transport, as determined by inhibition studies, with a Km of 6 mM. In addition, fructose transport by GLUT5 is not inhibited by cytochalasin B, a competitive inhibitor of facilitative glucose transporters. RNA and protein blotting studies showed the presence of high levels of GLUT5 mRNA and protein in human testis and spermatozoa, and immunocytochemical studies localize GLUT5 to the plasma membrane of mature spermatids and spermatozoa. The biochemical properties and tissue distribution of GLUT5 are consistent with a physiological role for this protein as a fructose transporter. PMID- 1634505 TI - Lipopolysaccharide priming of alveolar macrophages for enhanced synthesis of prostanoids involves induction of a novel prostaglandin H synthase. AB - We report here that lipopolysaccharide (LPS) priming of rabbit alveolar macrophages leads to amplified synthesis of prostanoids, at least in part, by induction of a novel prostaglandin H synthase (PGH synthase). Rabbit alveolar macrophages were cultured with or without added LPS derived from Escherichia coli 0111:B4 for 4 h and then stimulated with opsonized zymosan (OPZ). LPS priming of alveolar macrophages resulted in enhanced release of thromboxane (TX) upon stimulation with OPZ, when compared to stimulated non-LPS controls. Addition of exogenous arachidonic acid to LPS-primed alveolar macrophages also resulted in increased production of TX. The LPS-induced increase in TX formation, in response to OPZ or arachidonic acid, was abolished by the addition of actinomycin D or cycloheximide during the priming period. Gas chromatography/mass spectrometry analysis indicated that levels of prostaglandins D2, E2, and F2 alpha, along with TX, were augmented in stimulated LPS-primed alveolar macrophages, implicating PGH synthase in the priming process. PGH synthase enzymatic activity, as determined by addition of arachidonic acid to macrophage sonicates, was markedly enhanced in LPS-primed alveolar macrophages. This correlated with increased PGH synthase levels detected by immunoprecipitation of 35S-labeled proteins and by Western blot analysis. Finally, Northern blot analysis using a cDNA probe to the recently described mitogen-inducible mouse PGH synthase revealed strong induction of approximately 4.3-kilobase mRNA in LPS-primed alveolar macrophages. Taken together, these results reveal that induction of a novel PGH synthase, probably the rabbit homologue of PGH synthase-2, plays a role in the enhanced synthesis of prostanoids by LPS-primed alveolar macrophages. PMID- 1634507 TI - Synthesis of platelet-activating factor by polymorphonuclear neutrophils stimulated with interleukin-8. AB - Human interleukin-8 (IL-8) was evaluated for its capability to induce the synthesis and release of platelet-activating factor (PAF) from human polymorphonuclear neutrophils (PMN). IL-8 promotes in a dose-dependent fashion (1 100 ng/ml) a rapid synthesis of PAF, which is only partially released. The synthesis of PAF is preceded by the activation of acetyl-CoA: 1-alkyl-2-lyso-sn glycero-3-phosphocholine acetyl-transferase, suggesting that IL-8 activates the "remodeling pathway" of PAF synthesis. By thin layer chromatography and reverse phase high pressure liquid chromatography, we demonstrated that PAF synthesized by human PMN stimulated with IL-8 is heterogeneous: the 2-acetylated phospholipids having the biological and physicochemical characteristics of PAF include the 1-O-alkyl form, which is produced in large extent (51%), and the 1 acyl form (20%). The analysis of the individual molecular species of radyl chain indicated nine peaks, 16:0 and 18:0 being the predominant forms. These results identify PAF as a direct product of IL-8 stimulation in PMN. PMID- 1634506 TI - Serine regulates phosphatidylethanolamine biosynthesis in the hamster heart. AB - The role of serine as a precursor and metabolic regulator for phosphatidylethanolamine biosynthesis in the hamster heart was investigated. Hearts were perfused with 50 microM [1-3H]ethanolamine in the presence or absence of serine for up to 60 min. Ethanolamine uptake was attenuated by 0.05-10 mM serine in a noncompetitive manner, and the incorporation of labeled ethanolamine into phosphatidylethanolamine was also inhibited by serine. Analysis of the ethanolamine-containing metabolites in the CDP-ethanolamine pathway revealed that the conversion of ethanolamine to phosphoethanolamine was reduced. The reduction was a result of an inhibition of ethanolamine kinase activity by an elevated pool of intracellular serine. Perfusion of the heart with 1 mM serine caused a 5-fold increase in intracellular serine pool. In order to examine the action of serine on other phosphatidylethanolamine metabolic pathways, hearts were perfused with [1-3H]glycerol in the presence and absence of serine. Serine did not cause any enhancement of phosphatidylethanolamine hydrolysis. The base-exchange reaction for phosphatidylserine formation or the decarboxylation of phosphatidylserine was not affected by serine perfusion. We conclude that circulating serine plays an important role in the modulation of phosphatidylethanolamine biosynthesis via the CDP-ethanolamine pathway in the hamster heart but does not affect the contribution of the decarboxylase pathway for phosphatidylethanolamine formation. PMID- 1634508 TI - Functional interactions of stimulatory and inhibitory GDP/GTP exchange proteins and their common substrate small GTP-binding protein. AB - smg GDS and rho GDI are stimulatory and inhibitory GDP/GTP exchange proteins, respectively, for a group of ras p21-related small GTP-binding proteins (G proteins). rho p21 is a common substrate small G protein for both GDP/GTP exchange proteins. We examined here the functional interactions of these GDP/GTP exchange proteins with rho p21 as a substrate. smg GDS and rho GDI interacted with the GDP-bound form of rho p21 and thereby stimulated and inhibited, respectively, the dissociation of GDP. The inhibitory effect of rho GDI was much stronger than the stimulatory effect of smg GDS. The GDP-bound form of rho p21 formed a complex with rho GDI but not with smg GDS in their simultaneous presence. Since the content of smg GDS was generally less than that of rho GDI in cells, these results suggest that there is some mechanism to release the inhibitory action of rho GDI and to make rho p21 sensitive to the smg GDS action during the conversion of rhoA p21 from the GDP-bound inactive form to the GTP bound active form in intact cells. On the other hand, rho p21 was previously shown to be ADP-ribosylated by bacterial ADP-ribosyltransferases, named C3 and EDIN, at Asn41 in the putative effector region of rho p21. This ADP-ribosylation was inhibited by rho GDI much more efficiently than by smg GDS. These results suggest that rho GDI may mask the putative effector region of rho p21 and thereby inhibit its interaction with the target protein even in the presence of smg GDS. Thus, both smg GDS and rho GDI are important to regulate the rho p21 activity and action in cooperation with each other. PMID- 1634509 TI - S(T)PXX motifs promote the interaction between the extended N-terminal tails of histone H2B with "linker" DNA. AB - The assembly of hybrid core particles onto long chicken DNA with histone H2B in the chicken histone octamer replaced with either wheat histone H2B(2) or sea urchin sperm histone H2B(1) or H2B(2) is described. All these histone H2B variants have N-terminal extensions of between 18 and 20 amino acids, although only those from sea urchin sperm have S(T)PXX motifs present. Whereas chicken histone octamers protected 167 base pairs (bp) (representing two full turns) of DNA against micrococcal nuclease digestion (Lindsey, G. G., Orgeig, S., Thompson, P., Davies, N., and Maeder, D. L. (1991) J. Mol. Biol. 218, 805-813), all the hybrid histone octamers protected an additional 17-bp DNA against nuclease digestion. This protection was more marked in the case of hybrid octamers containing sea urchin sperm histone H2B variants and similar to that described previously (Lindsey, G. G., Orgeig, S., Thompson, P., Davies, N., and Maeder, D. L. (1991) J. Mol. Biol. 218, 805-813) for hybrid histone octamers containing wheat histone H2A variants all of which also have S(T)PXX motifs present. Continued micrococcal nuclease digestion reduced the length of DNA associated with the core particle via 172-, 162-, and 152-bp intermediates until the 146-bp core particle was obtained. These DNA lengths were approximately 5 bp or half a helical turn longer than those reported previously for stripped chicken chromatin and for core particles containing histone octamers reconstituted using "normal" length histone H2B variants. This protection pattern was also found in stripped sea urchin sperm chromatin, demonstrating that the assembly/digestion methodology reflects the in vivo situation. The interaction between the N-terminal histone H2B extension and DNA of the "linker" region was confirmed by demonstrating that stripped sea urchin sperm chromatin precipitated between 120 and 500 mM NaCl in a manner analogous to unstripped chromatin whereas stripped chicken chromatin did not. Tryptic digestion to remove all the histone tails abolished this precipitation as well as the protection of DNA outside of the 167-bp core particle against nuclease digestion. PMID- 1634510 TI - Processing of proinsulin by transfected hepatoma (FAO) cells. AB - Rat hepatoma (FAO) cells were stably transfected with the gene encoding either rat proinsulin II (using the DOL retroviral vector) or human proinsulin (using the RSV retroviral vector). Using the DOL vector, production of insulin immunoreactive material was stimulated up to 30-fold by dexamethasone (5 x 10(-7) M). For both proinsulins, fractional release of immunoreactive material relative to cellular content was high, in keeping with the absence of any storage compartment for secretory proteins in these cells. Pulse-chase experiments showed kinetics of release of newly synthesized products in keeping with release via the constitutive pathway. High performance liquid chromatography analysis showed immunoreactivity in the medium distributed between three peaks. For rat proinsulin II, the first coeluted with intact proinsulin; the second coeluted with des-64,65 split proinsulin (the product of endoproteolytic attack between the insulin A-chain and C-peptide followed by trimming of C-terminal basic residues by carboxypeptidase); the third (and minor peak) coeluted with native (fully processed) insulin. For human proinsulin, by contrast, the second peak coeluted with des-31,32 split proinsulin (split and trimmed at the B-chain/C peptide junction). Analysis of cellular extracts showed intact proinsulin as the major product. The generation of the putative conversion intermediates and insulin was not due to proteolysis of proinsulin after its release but rather to an intracellular event. The data suggest that proinsulin, normally processed in secretory granules and released via the regulated pathway, may also be processed, albeit less efficiently, by the constitutive pathway conversion machinery. The comparison of the sites preferentially cleaved in rat II or human proinsulin suggests cleavage by endoprotease(s) with a preference for R/KXR/KR as substrate. PMID- 1634511 TI - Choline transport into rat liver mitochondria. Characterization and kinetics of a specific transporter. AB - Rat liver mitochondria possess a specific choline transporter in the inner membrane. The transporter shows saturable kinetics at high membrane potential with a Km of 220 microM and a Vmax of 0.4 nmol/mg of protein/min at pH 7.0 and 25 degrees C. At physiological concentrations of choline, the rate of choline uptake by the transporter shows a linear dependence on membrane potential; uptake is distinct from the nonspecific cation diffusion process. Hemicholinium-3, hemicholinium-15, quinine, and quinidine, all analogues of choline, are high affinity competitive inhibitors of choline transport with Ki values of 17, 55, 15, and 127 microM, respectively. The choline transporter is distinct from other known mitochondrial transporters. Rat heart mitochondria do not appear to possess a choline transporter. Evidence suggests that the transporter is an electrophoretic uniporter. Analogue studies have shown that the hydroxyl and the quaternary ammonium groups of choline are necessary for binding to the transporter. A comparison of molecular models of choline and the high affinity inhibitors has provided evidence for the preferred conformation of choline for binding to the transporter. The presence of a choline transporter in the mitochondrial inner membrane provides a potential site for control of choline oxidation and hence supply of endogenous betaine. PMID- 1634512 TI - Relation between the insulin receptor number in cells, autophosphorylation and insulin-stimulated Ras.GTP formation. AB - We showed previously that upon insulin stimulation of an insulin receptor overexpressing cell line, most of the p21ras was rapidly converted into the GTP bound state (Burgering, B. M. T., Medema, R. H., Maassen, J. A., Van de Wetering, M. L., Van der Eb, A. J., McCormick, F., and Bos, J. L. (1991) EMBO J. 10, 1103 1109). To determine whether this process also occurs in cells expressing physiologically relevant numbers of insulin receptors, insulin stimulated Ras.GTP formation was quantitated in Chinese hamster ovary (CHO)-derived cell lines expressing varying numbers of insulin receptors. In the parental CHO9 cells, expressing only 5.10(3) insulin receptors, insulin stimulation for 3 min increased Ras.GTP levels with 10%. Upon increasing the number of insulin receptors in these cells, Ras.GTP levels increased almost proportionally until a plateau value of 60% is reached at high receptor numbers. These data show that receptor overexpression is not a prerequisite for insulin-stimulated Ras.GTP formation. The yield of Ras.GTP generated is 0.2-1.0 mol/mol autophosphorylated insulin receptor in CHO9- and NIH3T3-derived cell lines, respectively. These values argue against signal-amplifying processes between the insulin receptor and p21ras. To determine whether receptor autophosphorylation is required for Ras.GTP formation, NIH3T3 cells overexpressing insulin receptors were stimulated with a monoclonal antibody which activates the receptor and subsequent glucose transport without inducing detectable autophosphorylation. Also, CHO cells expressing the mutant Ser1200 receptor, which has markedly impaired tyrosyl autophosphorylation but is capable of mediating insulin-stimulated metabolic effects in CHO cells, were used. In both cases, no Ras.GTP formation was observed. Furthermore, Rat-1 derived cell lines expressing mutant p21ras, which is permanently in the active GTP-bound form, still responded to insulin by increasing the glucose uptake. These results support our hypothesis that Ras.GTP formation is activated by the tyrosyl-phosphorylated insulin receptor and suggest that an active Ras.GTP complex does not mediate metabolic signaling. PMID- 1634513 TI - Metabolic pathways of heparan sulfate proteoglycans in a rat parathyroid cell line. AB - The distribution of heparan sulfate (HS) proteoglycans in clonal rat parathyroid cells is regulated by the extracellular Ca2+ concentration, which is a principal factor for parathyroid cell function (Takeuchi, Y., Sakaguchi, K., Yanagishita, M., Aurbach, G. D., and Hascall, V. C. (1990) J. Biol. Chem. 265, 13661-13668). Increasing the concentration of extracellular Ca2+ in the physiological range redistributes HS proteoglycans from the cell surface to an intracellular compartment. We have now examined effects of the extracellular Ca2+ concentration on the metabolism of the HS proteoglycans in detail using [35S]sulfate metabolic labeling-chase experiments. Two distinct metabolic pathways were demonstrated: (i) the intracellular generation of HS chains from HS proteoglycans in prelysosomal compartments followed by their release into the medium (pathway 1), and (ii) intracellular generation of HS oligosaccharides from HS chains in prelysosomal compartments, which are eventually degraded into free sulfate in lysosomes (pathway 2). The HS oligosaccharides were exclusively present within the cells, whereas HS chains were found primarily in the medium. The cells do not internalize either HS proteoglycans or HS chains from the medium. These observations indicate that these two degradation pathways are independent. In addition to these pathways, approximately 15% of the HS proteoglycans were released into the medium as a proteoglycan form. Treatment of cells with chloroquine, a lysosomotropic agent, did not affect generation of HS chains but inhibited conversion of HS chains to HS oligosaccharides or to free sulfate and resulted in the release of HS chains from the cells. The drug did not affect metabolic pathway 1. The extracellular Ca2+ concentration did not alter these intracellular degradation pathways for HS proteoglycans in the parathyroid cells. Thus, extracellular Ca2+ appears to regulate only the distribution of HS proteoglycans between the cell surface and intracellular compartments, and the process of cycling between these compartments when extracellular Ca2+ is low. PMID- 1634514 TI - Recycling of transferrin receptors and heparan sulfate proteoglycans in a rat parathyroid cell line. AB - We examined recycling of heparan sulfate (HS) proteoglycans and transferrin receptor (Tf-R) in a rat parathyroid cell line. While extracellular Ca2+ concentration ([Ca2+]e) regulates the recycling of HS proteoglycans in parathyroid cells, such that HS proteoglycans only recycle when [Ca2+]e is lowered below physiological levels, recycling of Tf-R occurs equally well both in 0.05 mM (low) and 2 mM (high) [Ca2+]e. Inhibiting endocytosis chemically with phenylarsine oxide or at low temperature (4 degrees C) did not abolish the effects of changing [Ca2+]e on HS proteoglycans in the recycling compartment even though transport of HS proteoglycans from the Golgi complex to the cell surface was inhibited in low [Ca2+]e. Microtubules are not involved in the recycling of HS proteoglycans or of Tf-R since nocodazole did not affect these processes. Inhibiting the increase of intracellular Ca2+ by an intracellular Ca2+ chelator sustained recycling of HS proteoglycans even in the presence of high [Ca2+]e. These observations show that the exocytosis pathway of HS proteoglycans in the recycling compartment is specifically regulated by [Ca2+]e, whereas that for constitutive secretion is not. Therefore, the recycling of HS proteoglycans may be directly related to some functions of parathyroid cells regulated by [Ca2+]e. Although the mechanism by which [Ca2+]e regulates the exocytosis and recycling of HS proteoglycans is uncertain, it is suggested that an increase of intracellular Ca2+ is necessary, but not necessarily sufficient, for inhibiting their exocytosis. PMID- 1634515 TI - cis-acting elements that confer lung epithelial cell expression of the CC10 gene. AB - To define cis-acting genetic elements responsible for cell-specific transcriptional regulation of the CC10 gene, DNA sequences spanning nucleotides 2338 to +49 of the rat CC10 gene were linked to a reporter gene coding for chloramphenicol acetyltransferase (CAT). In transient expression assays, CC10 sequences were capable of restricting CAT expression to a human lung adenocarcinoma cell line similar to pulmonary Clara cells. Transgenic mice harboring the hybrid RtCC10-CAT construct expressed high levels of CAT activity specifically within protein extracts of lung and trachea. Transcripts for the CAT reporter gene colocalized with those for the endogenous murine CC10 gene within the airways of transgenic mice. Functional analysis of deletion mutants identified stimulatory, inhibitory, and cell type-specific transcriptional regulatory elements. The results of gel retention and DNaseI protection assays suggest that a transcriptional stimulatory region located between -320 and -175, and a cell type-specific regulatory element located between -175 and +49, result from a series of protein-DNA interactions occurring at -220 to -205 and -128 to 86, respectively. Lung epithelial specific transcriptional regulatory elements described herein will be useful for expression of chimeric genes within epithelial cells lining the trachea, bronchi, and bronchioles of mice. PMID- 1634516 TI - Minimal essential domains specifying toxicity of the light chains of tetanus toxin and botulinum neurotoxin type A. AB - To define conserved domains within the light (L) chains of clostridial neurotoxins, we determined the sequence of botulinum neurotoxin type B (BoNT/B) and aligned it with those of tetanus toxin (TeTx) and BoNT/A, BoNT/C1, BoNT/D, and BoNT/E. The L chains of BoNT/B and TeTx share 51.6% identical amino acid residues whereas the degree of identity to other clostridial neurotoxins does not exceed 36.5%. Each of the L chains contains a conserved motif, HExxHxxH, characteristic for metalloproteases. We then generated specific 5'- and 3' deletion mutants of the L chain genes of TeTx and BoNT/A and tested the biological properties of the gene products by microinjection of the corresponding mRNAs into identified presynaptic cholinergic neurons of the buccal ganglia of Aplysia californica. Toxicity was determined by measurement of neurotransmitter release, as detected by depression of postsynaptic responses to presynaptic stimuli (Mochida, S., Poulain, B., Eisel, U., Binz, T., Kurazono, H., Niemann, H., and Tauc, L. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 7844-7848). Our studies allow the following conclusions. 1) Residues Cys439 of TeTx and Cys430 of BoNT/A, both of which participate in the interchain disulfide bond, play no role in the toxification reaction. 2) Derivatives of TeTx that lacked either 8 amino- or 65 carboxyl-terminal residues are still toxic, whereas those lacking 10 amino- or 68 carboxyl-terminal residues are nontoxic. 3) For BoNT/A, toxicity could be demonstrated only in the presence of added nontoxic heavy (H) chain. A deletion of 8 amino-terminal or 32 carboxyl-terminal residues from the L chain had no effect on toxicity, whereas a removal of 10 amino-terminal or 57 carboxyl terminal amino acids abolished toxicity. 4) The synergistic effect mediated by the H chain is linked to the carboxyl-terminal portion of the H chain, as demonstrated by injection of HC-specific mRNA into neurons containing the L chain. This finding suggests that the HC domain of the H chain becomes exposed to the cytosol during or after the putative translocation step of the L chain. PMID- 1634517 TI - A linoleic acid (8R)-dioxygenase and hydroperoxide isomerase of the fungus Gaeumannomyces graminis. Biosynthesis of (8R)-hydroxylinoleic acid and (7S,8S) dihydroxylinoleic acid from (8R)-hydroperoxylinoleic acid. AB - The fungus Gaeumannomyces graminis metabolized linoleic acid extensively to (8R) hydroperoxylinoleic acid, (8R)-hydroxylinoleic acid, and threo-(7S,8S) dihydroxylinoleic acid. When G. graminis was incubated with linoleic acid under an atmosphere of oxygen-18, the isotope was incorporated into (8R) hydroxylinoleic acid and 7,8-dihydroxylinoleic acid. The two hydroxyls of the latter contained either two oxygen-18 or two oxygen-16 atoms, whereas a molecular species that contained both oxygen isotopes was formed in negligible amounts. Glutathione peroxidase inhibited the biosynthesis of 7,8-dihydroxylinoleic acid. These findings demonstrated that the diol was formed from (8R) hydroperoxylinoleic acid by intramolecular hydroxylation at carbon 7, catalyzed by a hydroperoxide isomerase. The (8R)-dioxygenase appeared to metabolize substrates with a saturated carboxylic side chain and a 9Z-double bond. G. graminis also formed omega 2- and omega 3-hydroxy metabolites of the fatty acids. In addition, linoleic acid was converted to small amounts of nearly (65% R) racemic 10-hydroxy-8,12-octadecadienoic acid by incorporation of atmospheric oxygen. An unstable metabolite, 11-hydroxylinoleic acid, could also be isolated as well as (13R,13S)-hydroxy-(9E,9Z), (11E)-octadecadienoic acids and (9R,9S) hydroxy-(10E), (12E,12Z)-octadecadienoic acids. In summary, G. graminis contains a prominent linoleic acid (8R)-dioxygenase, which differs from the lipoxygenase family of dioxygenases by catalyzing the formation of a hydroperoxide without affecting the double bonds of the substrate. PMID- 1634518 TI - Partially folded state of the disulfide-reduced form of human serum albumin as an intermediate for reversible denaturation. AB - The conformation of the fully disulfide-reduced state of human serum albumin was investigated by tryptophan fluorescence spectrum, CD analyses, and size-exclusion chromatography. Both the reduction of the native disulfide-bonded form under nondenaturing conditions and the refolding of the urea-denatured disulfide reduced form under reduced conditions yielded almost exactly the same disulfide reduced state with partially folded unique conformation that was clearly distinguished from either the native or fully denatured state. In addition, the interconversion between the urea-denatured reduced form and the partially folded reduced form was reversible with each other; by reoxidation, the partially folded reduced form was converted to the disulfide-bonded form. The conformation of disulfide-reduced serum albumin was highly variable depending on pH and ionic strength conditions. Thus, we concluded that the disulfide-reduced state with partially folded variable conformation is involved in the reversible interconversion between the denatured reduced form and the native disulfide bonded form of human serum albumin. PMID- 1634519 TI - Construction, expression, and characterization of a chimera of factor IX and factor X. The role of the second epidermal growth factor domain and serine protease domain in factor Va binding. AB - The prothrombinase complex, which catalyzes the conversion of prothrombin to thrombin, consists of activated Factor X, Factor Va, a membrane surface and Ca2+. To examine the structures that support Factor Va binding to Factor X, we used in vitro mutagenesis to construct a chimeric molecule that includes regions of Factor IX and Factor X. This chimera (IXGla,E1XE2,SP) was prepared from cDNA encoding the second epidermal growth factor (EGF) and serine protease domains of Factor X linked downstream from the cDNA encoding the signal peptide, propeptide, Gla domain, and first EGF domain of Factor IX. The cDNAs encoding the Factor IX/X chimera and wild-type Factor X were each expressed in Chinese hamster ovary cells and the secreted proteins purified by affinity chromatography using polyclonal anti-Factor X antibodies. The chimera migrated as a single major band corresponding to a molecular weight of 68,000. By Western blotting, the chimeric protein stained with both polyclonal anti-Factor X and anti-Factor IX antibodies. gamma-Carboxyglutamic acid analysis demonstrated near complete carboxylation of both the wild-type Factor X and the Factor IX/X chimera. Compared with Factor X, the rate of zymogen activation of the Factor IX/X chimera was about 50% that of Factor X when activated by Factor IXa, Factor VIIIa, phospholipid, and Ca2+. The enzyme form of the Factor IX/X chimera, activated Factor IX/X, generated using the coagulant protein of Russell's viper venom, expressed full amidolytic activity compared with Factor Xa. The activated Factor IX/X chimera had about 14% of the activity of Factor Xa when employed in a prothrombinase assay; this activity reached 100% with increasing concentrations of Factor Va. A binding assay was employed to test the ability of the active site-inactivated Factor IX/Xa chimera to inhibit the binding of Factor Xa to the Factor Va-phospholipid complex, thus inhibiting the activation of prothrombin to thrombin. In this assay the active site-inactivated form of the chimera competed with Factor Xa completely but with decreased affinity for the Factor Va-phospholipid complex. These data indicate that the second EGF domain and the serine protease domain of Factor Xa are sufficient to interact with Factor Va. The Factor IX/X chimera is a good substrate for the tenase complex; the defective enzymatic activity of the activated Factor IX/X chimera can be accounted for by its decreased affinity for Factor Va relative to Factor Xa. PMID- 1634520 TI - Structure and function in rhodopsin. Studies of the interaction between the rhodopsin cytoplasmic domain and transducin. AB - Structural requirements for the activation of transducin by rhodopsin have been studied by site-specific mutagenesis of bovine rhodopsin. A variety of single amino acid replacements and amino acid insertions and deletions of varying sizes were carried out in the two cytoplasmic loops CD (amino acids 134-151) and EF (amino acids 231-252). Except for deletion mutant delta 137-150, all the mutants bound 11-cis-retinal and displayed normal spectral characteristics. Deletion mutant delta 236-239 in loop EF caused a 50% reduction of transducin activation, whereas deletion mutant delta 244-249 and the larger deletions in loop EF abolished transducin activation. An 8-amino acid deletion in the cytoplasmic loop CD as well as a replacement of 13 amino acids with an unrelated sequence showed no transducin activation. Several single amino acid substitutions also caused significant reduction in transducin activation. The conserved charged pair Glu 134/Arg-135 in the cytoplasmic loop CD was required for transducin activation; its reversal or neutralization abolished transducin activation. Three amino acid replacements in loop EF (S240A, T243V, and K248L) resulted in significant reduction in transducin activation. We conclude that 1) both the cytoplasmic loops CD and EF are required for transducin activation, and 2) effective functional interaction between rhodopsin and transducin involves relatively large peptide sequences in the cytoplasmic loops. PMID- 1634521 TI - Properties of human red cell spectrin heterodimer (side-to-side) assembly and identification of an essential nucleation site. AB - The antiparallel side-to-side association of spectrin alpha and beta monomers is a two-step process which occurs in seconds even at 0 degrees C and at low concentrations. Assembly involves initial contact of complementary nucleation sites on each subunit, which are located near the actin binding end of the long, flexible heterodimer rod. The minimum nucleation sites are comprised of approximately four contiguous 106-residue homologous segments or repeats. Three repeats in the nucleation site contain an 8-residue insertion and have the highest homology to the four spectrin-like repeats in alpha-actinin. The adjacent actin binding domain on the beta subunit and the adjacent EF hand motifs on the alpha subunit are not required for heterodimer assembly. The nucleation sites probably have a specific lock and key structure which defines the unique side-to side pairing of the many homologous segments in both subunits. Assembly of spectrin heterodimers is probably most analogous to a zipper. After initial nucleation site binding, the remainder of the subunits quickly associate along their full lengths to reconstitute a normal dimer by supercoiling around each other to form a rope-like, flexible rod. Assembly is terminated if either polypeptide is interrupted by a protease cleavage. Heterozygotic mutations involving either nucleation site are predicted to affect allele incorporation into the mature membrane skeleton. PMID- 1634522 TI - Metabolic fate of plasma membrane diacylglycerols in NIH 3T3 fibroblasts. AB - We have examined the metabolism of three radiolabeled 1,2-diacylglycerols (DGs) in NIH 3T3 fibroblasts. Since the lipids used are not appreciably taken up by the cells, we used a phosphatidylserine (PS)-based liposome fusion system to rapidly associate the lipid species with the plasma membrane. When 1,2-[1-14C]dioleoyl-sn 3-glycerol ([14C]DOG) is delivered in this way, it is rapidly converted predominantly to phosphatidylcholine (PC) and triacylglycerol (TG) and to a lesser extent, to monoacylglycerol (MG) and fatty acids (FA), as well as phosphatidic acid (PA) and phosphatidylinositol (PI). We present evidence that [14C] DOG is largely utilized as an intact molecule rather than being broken down to FA and then incorporated to cell lipids. Examination of the metabolism of 1 stearoyl-2-[1-14C]myristoyl-sn-3-glycerol ([14C]SMG) and 1-stearoyl-2 arachidonoyl-sn-3-glycerol ([14C]SAG) reveal important differences. Both produce substantial labeling of PC but [14C]SMG gives rise to the highest proportion of TG and the lowest of PA and PI, whereas [14C]SAG yields the opposite pattern. When phosphatidic acid labeled on its glycerol backbone (1,2-dioleoyl-sn-[U-14C] glycero-3-phosphate) was supplied to the cells via the liposomes, rapid appearance of labeled DG was found which then decreased with concomitant labeling of cellular PC and TG. Only small amounts of the glycerol backbone were recovered in PI. Our experiments identify three types of processes involved in the metabolism of plasma membrane DGs: (i) transferase-catalyzed conversions to PC and TG, (ii) lipolytic breakdown to MG and FA, and (iii) phosphorylation to PA and then conversion to PI. The relative proportions of each DG species converted to these different products are strongly dependent on the fatty acyl composition of the particular DG molecular species, even though formation of PC is the major event in all cases. Since DGs are important second messengers, our study supports the view that conversion to PC and TG can play a key role in DG signal attenuation. PMID- 1634523 TI - Phytochrome assembly. The structure and biological activity of 2(R),3(E) phytochromobilin derived from phycobiliproteins. AB - The unicellular rhodophyte, Porphyridium cruentum, and the filamentous cyanobacterium, Calothrix sp. PCC 7601, contain phycobiliproteins that have covalently bound phycobilin chromophores. Overnight incubation of solvent extracted cells at 40 degrees C with methanol liberates free phycobilins that are derived from the protein-bound bilins by methanolytic cleavage of the thioether linkages between bilin and apoprotein. Two of the free bilins were identified as 3(E)-phycocyanobilin and 3(E)-phycoerythrombilin by comparative spectrophotometry and high pressure liquid chromatography. Methanolysis also yields a third bilin free acid whose absorption and 1H NMR spectra support the assignment of the 3(E) phytochromobilin structure. This novel bilin is the major pigment isolated from cells that are pre-extracted with acetone-containing solvents. Since phytochrome- or phytochromobilin-containing proteins are not present in either organism, the 3(E)-phytochromobilin must arise by oxidation of phycobilin chromophores. This pigment is not obtained by similar treatment of a cyanobacterium and a rhodophyte that lack phycoerythrin. Therefore, 3(E)-phytochromobilin appears to be derived from phycoerythrobilin-containing proteins. Comparative CD spectroscopy of 3(E) phytochrombilin and 3(E)-phycocyanobilin suggests that the two bilins share the R stereochemistry at the 2-position in the reduced pyrrole ring. Incubation of 2(R),3(E)-phytochromobilin with recombinant oat apophytochrome yields a covalent bilin adduct that is photoactive and spectrally indistinguishable from native oat phytochrome isolated from etiolated seedlings. These results establish that the phycobiliprotein-derived 2(R),3(E)-phytochromobilin is a biologically active phytochrome chromophore precursor. PMID- 1634524 TI - Multiple forms of ubiquitin-activating enzyme E1 from wheat. Identification of an essential cysteine by in vitro mutagenesis. AB - Ubiquitin-activating enzyme, E1, directs the ATP-dependent formation of a thiol ester linkage between itself and ubiquitin. The energy in this bond is ultimately used to attach ubiquitin to various intracellular proteins. We previously reported the isolation of multiple E1s from wheat and the characterization of a cDNA encoding this protein (UBA1). We now report the derived amino acid sequence of two additional members of this gene family (UBA2 and UBA3). Whereas the amino acid sequence of UBA2 is nearly identical to UBA1, the sequence of UBA3 is significantly different. Nevertheless, the protein encoded by UBA3 catalyzes the ATP-dependent activation of ubiquitin in vitro. Comparison of derived amino acid sequences of genes encoding E1 from plant, yeast, and animal tissues revealed 5 conserved cysteine residues, with one potentially involved in thiol ester bond formation. To identify this essential residue, codons corresponding to each of the 5 cysteines in UBA1 were individually altered using site-directed mutagenesis. The mutagenized enzymes were expressed in Escherichia coli and assayed for their ability to activate ubiquitin. Only substitution of the cysteine at position 626 abolishes E1 activity, suggesting that this residue forms the thiol ester linkage with ubiquitin. PMID- 1634525 TI - Characterization of the multisubunit cleavage-polyadenylation specificity factor from calf thymus. AB - Cleavage-polyadenylation specificity factor (CPSF) is one of five separable factors known to be required for 3' cleavage and polyadenylation of mRNA precursors in vitro. Previous studies have shown that the cleavage and poly(A) addition reactions can be uncoupled in vitro and have suggested that CPSF may be the only factor essential for both of these subreactions. Here we report the purification of CPSF to near homogeneity from calf thymus and show that the purified factor contains three polypeptides of 165, 105, and 70 kDa. These polypeptides cosediment precisely with CPSF activity, which has a sedimentation coefficient of 11.5 S. Consistent with previous reports from our laboratory, purified CPSF does not contain a detectable RNA component, indicating that it is a multisubunit protein and not a small nuclear ribonucleoprotein. Extensively purified bovine CPSF can function with human poly(A) polymerase to bring about AAUAAA-dependent poly(A) addition or with human cleavage factors to catalyze accurate 3' cleavage of a pre-mRNA substrate. UV cross-linking and gel retention analyses demonstrate that highly purified CPSF interacts with one of these cleavage factors, the multisubunit cleavage-stimulation factor, to facilitate stable binding of both to an AAUAAA-containing pre-mRNA. Likewise, evidence is presented indicating that poly(A) polymerase and CPSF can interact directly. PMID- 1634526 TI - Eosinophil-derived neurotoxin and human liver ribonuclease. Identity of structure and linkage of neurotoxicity to nuclease activity. AB - Eosinophil-derived neurotoxin (EDN) and human liver RNase were found to be indistinguishable from each other but distinct from the pancreatic ribonucleases in their nucleolytic activity on polynucleotides or small defined substrates. Antibodies to EDN and liver RNase showed identical cross-reactivities in assays of nuclease inhibition and in a radioimmunoassay. In each instance, EDN and liver RNase were easily distinguished from bovine or human pancreatic RNase. When injected intrathecally into rabbits, 5-10 micrograms of EDN or liver RNase each was neurotoxic as judged by induction of the Gordon phenomenon. Human pancreatic RNase was less neurotoxic, and up to 20-fold higher levels of bovine pancreatic RNase showed no effect. Treatment of EDN, liver RNase, and eosinophil cationic protein with iodoacetic acid at pH 5.5 resulted in inactivation of their RNase activity and also destroyed their neurotoxicity. EDN conformation was not greatly affected by iodoacetate treatment since interaction of the modified protein with antibodies was only slightly altered. We conclude that RNase activity is necessary but not sufficient to induce neurotoxic action. PMID- 1634527 TI - NAD+ binding site of Clostridium botulinum C3 ADP-ribosyltransferase. Identification of peptide in the adenine ring binding domain using 2-azido NAD. AB - C3 ADP-ribosyltransferase is an exoenzyme produced by certain strains of Clostridium botulinum types C and D, which specifically ADP-ribosylates rho proteins in eukaryotic cells. Using the photoaffinity probe [alpha 32P]nicotinamide-2-azidoadenine dinucleotide, we have identified the adenine ring binding domain of the NAD+ binding site. The specificity of labeling was demonstrated by saturation effects and protection by the natural compound at physiologically relevant concentrations. Saturation of labeling was observed at 50 microM. Protection experiments indicated an 80% protection of labeling by 100 microM NAD+ when protein was photolyzed in the presence of 10 microM probe. Trypsin or Staphylococcus aureus V8 protease digestion of the photolabeled protein, along with boronate affinity chromatography and immobilized metal affinity chromatography, was used to specifically isolate the peptide region photolabeled with the probe. The peptide corresponded to Phe9-Gly19 near the N terminus. PMID- 1634528 TI - Cytoplasmic and mitochondrial tRNA nucleotidyltransferase activities are derived from the same gene in the yeast Saccharomyces cerevisiae. AB - ATP (CTP):tRNA-specific tRNA nucleotidyltransferase is an enzyme required for the synthesis of functional tRNAs in eukaryotic cells. Neither the tRNA genes in the nucleus nor in organelles encode the CCA end, so it must be added post transcriptionally. The gene that codes for the enzyme that adds the CCA end to nuclear coded tRNAs in Saccharomyces cerevisiae has been isolated (Aebi, M., Kirchner, G., Chen, J.-Y., Vijayraghavan, U., Jacobson, A., Martin, N. C., and Abelson, J. (1990) J. Biol. Chem. 265, 16216-16220). We now demonstrate that there is a mitochondrial tRNA nucleotidyltransferase activity in yeast and that it is a matrix enzyme. A comparison of purified mitochondrial enzyme with its cytoplasmic counterpart revealed no differences. These results suggest that proteins responsible for this step in the maturation of tRNAs in the nucleus and mitochondria might be identical and coded by the same nuclear gene. Accumulation of shortened mitochondrial as well as cytoplasmic tRNAs in a strain with a temperature-sensitive tRNA nucleotidyltransferase is consistent with this hypothesis. Alteration of the wild type gene such that amino-terminal truncated proteins are produced leads to a defect in mitochondrial function and a decrease in mitochondrial nucleotidyltransferase activity. This provides a direct demonstration that one gene provides this enzyme activity for the biosynthesis of tRNAs in both the nuclear/cytoplasmic and mitochondrial compartments in yeast. PMID- 1634529 TI - A native RNA secondary structure controls alternative splice-site selection and generates two human growth hormone isoforms. AB - Consensus sequences at the splice donor, splice acceptor, and lariat branch point regions are necessary but insufficient determinants of splice-site selection in nuclear precursor mRNAs. Sequences outside of these regions can have a significant effect on the utilization of splice sites. Although the mode of action of such sequences is undefined in most cases, higher order RNA structures have been suggested as a potential contributor to splice-site selection. During a detailed analysis of the splicing patterns of the human growth hormone transcript, we located 2 bases in the vicinity of the exon 3 major splice acceptor site (B) which facilitate the utilization of a competing downstream acceptor (B'). The effects of a series of site-specific mutations on the splicing pattern demonstrate that these 2 bases function by stabilizing a specific stem loop structure in the native transcript. This defined secondary structure selectively encompasses the upstream B splice-acceptor site together with its lariat branch point region. Increasing the predicted stability of this stem by point mutations results in a corresponding shift in splicing towards the alternative B' splice-acceptor site. These results indicate that a specific secondary structure within the native human growth hormone transcript controls the relative utilization of two competing splice-acceptor sites with the consequent generation of two functionally distinct hormone isoforms. PMID- 1634530 TI - Brefeldin A promotes hydrolysis of sphingomyelin. AB - The hydrolysis of sphingomyelin (SM) is a key reaction in the "sphingomyelin cycle," which plays a role in the regulation of cell proliferation and differentiation (Okazaki, T., Bell, R. M., and Hannun, Y. A. (1989) J. Biol. Chem. 264, 19076-19080). SM is produced from endoplasmic reticulum-derived ceramide and is delivered to organelle membranes in a regulated manner, presumably through the same endomembrane trafficking system used for sorting and delivery of proteins. Since brefeldin A (BFA) interferes with this endomembrane trafficking system and thus alters normal membrane and organelle distribution, we investigated the effect of BFA on SM levels in HL-60 leukemia cells. BFA caused a dose-dependent decrease of 20-25% in cellular SM levels, with effects observed at concentrations of BFA as low as 0.10 microgram/ml. BFA effects on SM levels were noted as early as 5 min and were maximal by 20 min, with no further SM hydrolysis observed up to 60 min following treatment with BFA, suggesting the presence of a fixed SM-sensitive pool. BFA did not cause SM hydrolysis at 16 degrees C, a temperature that inhibits the effects of BFA on endomembrane mixing. The very early effects and temperature dependence of BFA-induced SM hydrolysis suggest that the mechanism of hydrolysis may be closely related to endomembrane mixing. These studies are beginning to define important interrelationships between membrane trafficking and topology, SM metabolism, and cell regulation. PMID- 1634531 TI - Separation of human neutrophil plasma membrane from intracellular vesicles containing alkaline phosphatase and NADPH oxidase activity by free flow electrophoresis. AB - A putative reservoir of functional plasma membrane proteins, the secretory vesicle identified by latent alkaline phosphatase and tetranectin, has previously been demonstrated based on indirect evidence (Borregaard, N., Miller, L. J., and Springer, T. A. (1987) Science 237, 1204-1206; Borregaard, N., Christensen, L., Bjerrum, O. W., Birgens, H. S., and Clemmesen, I. (1990) J. Clin. Invest. 85, 408 416). Difficulties in separating plasma membranes from this entity by density gradient centrifugation has prohibited discriminative dynamic and quantitative studies of secretory vesicles and plasma membranes. By combining density centrifugation with free flow electrophoresis we overcame this obstacle. Freshly prepared unperturbed human neutrophils were subjected to nitrogen cavitation followed by density centrifugation on Percoll gradients. Light membrane fractions containing plasma membranes and secretory vesicles were applied to high voltage free flow electrophoresis on an Elphor VaP 22. Plasma membrane vesicles, identified by HLA class I antigen mixed enzyme-linked immunosorbent assay (Bjerrum, O. W., and Borregaard, N. (1990) Scand. J. Immunol. 31, 305-313) and 125I applied to cells before cavitation, were clearly separated from secretory vesicles. Electron microscopy revealed a morphology typical of plasma membranes in the former fraction and a population of vesicles with markedly different appearance in the latter. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles demonstrated distinct differences in protein patterns between the two fractions. Superoxide generating capacity induced by sodium dodecyl sulfate and cytosol, an entity traditionally ascribed to the plasma membrane, was largely confined to fractions containing secretory vesicles. Thus, the majority of membrane-bound NADPH oxidase components of light membranes of human neutrophils colocalize with secretory vesicles. PMID- 1634532 TI - Hexanoate and octanoate inhibit transcription of the malic enzyme and fatty acid synthase genes in chick embryo hepatocytes in culture. AB - Hexanoate and octanoate inhibit the triiodothyronine (T3)-induced increases in the activities of malic enzyme and fatty acid synthase in chick embryo hepatocytes in culture. Butanoate was less effective as an inhibitor, and palmitate, stearate, and oleate had no effect or small stimulatory effects. Hexanoate and octanoate inhibited the lipogenic enzyme activities at a transcriptional step, and did so within 30 min of addition. Incubation for 2 h in the absence of fatty acid reversed the inhibition of transcription caused by hexanoate. The inhibitory effect of hexanoate was selective because DNA content and transcription of the glyceraldehyde-3-phosphate dehydrogenase and beta-actin genes were not inhibited. Hexanoate-mediated inhibition of transcription rates of the lipogenic genes was not correlated with an inhibition of binding of T3 to its nuclear receptor. 2-Bromooctanoate and carnitine stimulated the T3-induced accumulation of the mRNAs for malic enzyme and fatty acid synthase. The presence of hexanoate stimulated by 2- to 3-fold the increase caused by carnitine, suggesting that hexanoate and carnitine may regulate lipogenic gene expression by a common pathway. Hexanedioate, acetoacetate, beta-hydroxybutyrate, branched chain fatty acids, and branched chain keto acids had little or no effect on abundance of the lipogenic mRNAs. We suggest that the active inhibitor is a metabolite derived from hexanoate or octanoate, possibly an intermediate derived from an acyl-CoA derivative. PMID- 1634533 TI - Specificity of photolabeling of beta-cell membrane proteins with an 125I-labeled glyburide analog. AB - The interaction between sulfonylureas and membrane proteins from a hamster insulin-secreting tumor (HIT) cell line has been examined. Four HIT cell membrane proteins were covalently linked to an 125I-labeled glyburide analog by photolabeling. Three photolabeled polypeptides of M(r) 65,000, 55,000, and 30,000 were identified as low affinity "glyburide receptors." These proteins appear to be of similar abundance, when quantitated by photolabeling, with half-maximal displacements (Ki values) by glyburide, glipizide, and tolbutamide in the low micromolar range. The glyburide analog is more tightly bound to a M(r) 140,000 protein with dissociation constants, determined by filtration binding assays and by photolabeling, of 7 and 9.0 nM, respectively. The labeled analog was displaced from the M(r) 140,000 protein by glyburide, glipizide and tolbutamide with Ki values of 3.3 nM, 103 nM, and 25 microM, respectively, as estimated by photolabeling. Optimal conditions established for visualizing the M(r) 140,000 band on autoradiograms prepared after UV cross-linking and sodium dodecyl sulfate polyacrylamide gel electrophoresis include irradiating the radioligand-receptor complex at 1.5 J/cm2 at 312 nm, followed by heating samples in pH 9.0 sodium dodecyl sulfate-gel sample buffer. With receptor sites partially occupied (5 nM radioligand), approximately 0.75% of the protein is photocoupled to the radioligand and visualized by autoradiography. Our results confirm that the M(r) 140,000 polypeptide contains the beta-cell high affinity glyburide binding site and show that the second generation sulfonylurea antidiabetic drugs have a selective increase in affinity for this receptor. PMID- 1634534 TI - Co-expression of sulfonylurea receptors and KATP channels in hamster insulinoma tumor (HIT) cells. Evidence for direct association of the receptor with the channel. AB - Cell membranes isolated from hamster insulinoma (HIT T15) cells at passages 65-74 contain high and low affinity receptors for a sulfonylurea derivative, 5 [125I]iodo,2-hydroxyglyburide (KD values of approximately 7 nM and 16 microM). Between passages 75 and 85, the estimated B(max) for the high affinity receptor decreases approximately 10-fold from approximately 1.6 to 0.16 pmol/mg membrane protein. By contrast, the density of low affinity binding sites, 800-1000 pmol/mg, is unaltered. The drop in high affinity receptors is paralleled by a decrease in the density of KATP channels assessed using patch-clamp and 86Rb(+) efflux techniques. These results strongly support the idea that the high affinity sulfonylurea receptor is an integral part of the KATP channel. PMID- 1634535 TI - Active-site-selective labeling of blood coagulation proteinases with fluorescence probes by the use of thioester peptide chloromethyl ketones. I. Specificity of thrombin labeling. AB - In a new strategy for labeling the active sites of serine proteinases with fluorescence probes (Bock, P. E. (1988) Biochemistry 27, 6633-6639), a thioester peptide chloromethyl ketone inhibitor is incorporated into the enzyme active center and used to produce a unique thiol group which provides a site for selective chemical modification with any one of many thiol-reactive fluorescence probes. This approach was developed to increase the opportunities for identifying fluorescent proteinase derivatives that act as reporters of binding interactions by allowing a large number of derivatives, representing a broad range of probe spectral properties, to be readily prepared. In the studies described here, the specificity of the labeling approach was evaluated quantitatively for the labeling of human alpha and beta/gamma-thrombin with the thioester peptide chloromethyl ketones, N alpha-[(acetylthio)acetyl]-D-Phe-Pro-Arg-CH2Cl and N alpha-[(acetylthio)acetyl]-D-Phe-Phe-Arg-CH2Cl, and the thiol-reactive fluorescence probe, 5-(iodoacetamido)fluorescein. Irreversible inactivation of thrombin by the inhibitors was accompanied by incorporation of 0.98 +/- 0.06 mol/mol of the thioester group into the active site, independent of a 470-fold difference between the thioester peptide chloromethyl ketones in the bimolecular rate constants of alpha-thrombin affinity labeling. Subsequent mild treatment of the covalent thrombin-inhibitor complexes with NH2OH in the presence of 5 (iodoacetamido)fluorescein resulted in generation of the thiol group together with its selective modification and incorporation of 0.96 +/- 0.07 mol of probe/mol of active sites. The incorporated label was localized to a 9000 molecular weight region of alpha and beta/gamma-thrombin containing the catalytic site histidine residue. Evaluation of competing, side reactions showed that they did not significantly compromise the active site specificity of labeling. These results demonstrated equivalent, active-site-selective fluorescence probe labeling of alpha and beta/gamma-thrombin by use of either of the thioester peptide chloromethyl ketones, with a site specificity of greater than or equal to 94%. PMID- 1634536 TI - Active-site-selective labeling of blood coagulation proteinases with fluorescence probes by the use of thioester peptide chloromethyl ketones. II. Properties of thrombin derivatives as reporters of prothrombin fragment 2 binding and specificity of the labeling approach for other proteinases. AB - The behavior of an array of fluorescent human alpha-thrombin derivatives in reporting binding of the fragment 2 domain of prothrombin was characterized as a representative application of the active-site-selective labeling approach to studies of blood coagulation proteinase regulatory interactions. An array of 16 thrombin derivatives was prepared by affinity labeling of the proteinase active site with the thioester peptide chloromethyl ketones, N alpha [(acetylthio)acetyl]-D-Phe-Pro-Arg-CH2Cl or N alpha-[(acetylthio)acetyl]-D-Phe Phe-Arg-CH2Cl, followed by selective modification of the NH2OH-generated thiol group on the covalently incorporated inhibitors with each of eight thiol-reactive fluorescence probes. The changes in probe fluorescence intensity of the derivatives, signaling changes in the environment of the catalytic site associated with fragment 2 binding, appeared to be a unique and unpredictable function of the structure of the probe and the connecting peptide. These results demonstrated the utility of the labeling approach for overcoming the problem of not being able to predict which fluorescent label will provide the most useful proteinase derivative for investigating an interaction by enabling a greater variety of them to be prepared and screened for those with the most desirable properties. To determine whether the approach could be extended to other proteinases, the specificity of labeling with the fluorescence probe iodoacetamide, 5-(iodoacetamido)fluorescein, by use of the two thioester inhibitors was evaluated for several other blood coagulation proteinases and related trypsin-like enzymes. All of the proteinases were labeled in an active site-selective manner. The combined results of quantitating the labeling reactions for the proteinase and inhibitor combinations studied thus far showed active-site-specific incorporation of 0.98 +/- 0.10 mol of inhibitor/mol of active sites and 0.92 +/- 0.11 mol of probe/mol of active sites, representing an overall greater than or equal to 93% site-specificity of labeling. These results demonstrated the broad applicability of the labeling approach for fluorescence studies of proteinases that differ greatly in their catalytic specificities. PMID- 1634537 TI - A novel disialoganglioside in rat spleen lymphocytes. AB - A novel ganglioside has been identified as the predominant disialoganglioside of the lymphocytes prepared from rat spleen. The ganglioside was isolated from rat spleen and characterized by compositional analysis, methylation analysis, sialidase hydrolysis, proton NMR spectroscopy, and negative ion fast atom bombardment mass spectrometry. The structure was determined as follows. [formula: see text] This ganglioside is a unique derivative of N-acetyllactosaminyl-GM1. The three monosialogangliosides containing N-acetyllactosaminyl-GM1 structure, which had been originally isolated from rat spleen (Nohara, K., Suzuki, M., Inagaki, F., Ito, H., and Kaya, K. (1990) J. Biol. Chem. 265, 14335-14339), were also found in the lymphocytes and were hardly detected in the spleen remnant tissue depleted of single cells. On the other hand, GD1c(NeuGc,NeuGc) (IV3(NeuGc alpha 2-8NeuGc)-Gg4Cer), the overwhelmingly predominant ganglioside of rat thymocytes (Nohara, K., Suzuki, M., Inagaki, F., and Kaya, K. (1991) J. Biochem. (Tokyo) 110, 274-278), was demonstrated to be only a minor component of the gangliosides of the spleen lymphocytes. These results suggested that GD1c is characteristic for the immature T lineage lymphoid cells and the gangliosides having lactosaminyl-GM1 structure are specific for other populations of the lymphocytes in rat. PMID- 1634538 TI - Purification and characterization of the bacteriophage T7 gene 2.5 protein. A single-stranded DNA-binding protein. AB - Bacteriophage T7 gene 2.5 protein has been purified to homogeneity from cells overexpressing its gene. Native gene 2.5 protein consists of a dimer of two identical subunits of molecular weight 25,562. Gene 2.5 protein binds specifically to single-stranded DNA with a stoichiometry of approximately 7 nucleotides bound per monomer of gene 2.5 protein; binding appears to be noncooperative. Electron microscopic analysis shows that gene 2.5 protein is able to disrupt the secondary structure of single-stranded DNA. The single-stranded DNA is extended into a chain of gene 2.5 protein dimers bound along the DNA. In fluorescence quenching and nitrocellulose filter binding assays, the binding constants of gene 2.5 protein to single-stranded DNA are 1.2 x 10(6) M-1 and 3.8 x 10(6) M-1, respectively. Escherichia coli single-stranded DNA-binding protein and phage T4 gene 32 protein bind to single-stranded DNA more tightly by a factor of 25. Fluorescence spectroscopy suggests that tyrosine residue(s), but not tryptophan residues, on gene 2.5 protein interacts with single-stranded DNA. PMID- 1634539 TI - Interactions of gene 2.5 protein and DNA polymerase of bacteriophage T7. AB - Bacteriophage T7 gene 2.5 protein has been shown to interact with T7 DNA polymerase (the complex of T7 gene 5 protein and Escherichia coli thioredoxin) by affinity chromatography and fluorescence emission anisotropy. T7 DNA polymerase binds specifically to a resin coupled to gene 2.5 protein and elutes from the resin when the ionic strength of the buffer is raised to 250 mM NaCl. In contrast, T7 gene 5 protein alone binds more weakly to gene 2.5 protein, eluting when the ionic strength of the buffer is 50 mM NaCl. Thioredoxin does not bind to gene 2.5 protein. Steady-state fluorescence emission anisotropy gives a dissociation constant of 1.1 +/- 0.2 microM for the complex of gene 2.5 protein and T7 DNA polymerase, with a ratio of gene 2.5 protein to T7 DNA polymerase in the complex of 1:1. Nanosecond emission anisotropic analysis suggests that the complex contains one monomer each of gene 2.5 protein, gene 5 protein, and thioredoxin. The ability of T7 gene 2.5 protein to stimulate the activity and processivity of T7 DNA polymerase is compared with the ability of three other single-stranded DNA-binding proteins: E. coli single-stranded DNA-binding protein, T4 gene 32 protein, and E. coli recA protein. All except E. coli recA protein stimulate the activity and processivity of T7 DNA polymerase; E. coli recA protein inhibits these activities. PMID- 1634540 TI - Partial purification, from Xenopus laevis oocytes, of an ATP-dependent activity required for nucleosome spacing in vitro. AB - A critical feature of chromatin with regard to structure and function is the regular spacing of nucleosomes. In vivo, spacing of nucleosomes occurs in at least two steps, but the mechanism is not understood. In this report, we have mimicked the two-step process in vitro. A novel spacing activity has been partially purified from Xenopus laevis ovaries. When this activity is added, either at the beginning or at the end of a nucleosomal assembly reaction, it can convert a DNA template consisting of irregularly spaced nucleosomes into a chromatin structure made up of regularly spaced nucleosomes with a repeat length of about 165 base pairs. The reaction requires ATP. Histone H1 is able to increase the nucleosomal repeat from 165 to 190 base pairs. This two-step increase in nucleosomal repeat length suggests that both the spacing activity and histone H1 contribute to generating repeat lengths of greater than 165 base pairs and that their contributions may be additive. Alternatively, the critical step in the spacing reaction may not be the formation of the 165-base pair repeat but may be the sliding of nucleosomes or the reorganization of the octamer structure induced by the spacing activity. PMID- 1634541 TI - Intracellular transit of a yeast protease is rescued by trans-complementation with its prodomain. AB - The alkaline extracellular protease (AEP) of the yeast Yarrowia lipolytica is synthesized as a preproprotein. The precursor undergoes a complex maturation during its intracellular transit, successively involving signal peptide cleavage, dipeptidyl aminopeptidase processing, and cleavage at a dibasic site which results in the extracellular release of the active enzyme. It was previously shown that various deletions within the proregion affect the intracellular transit of the protease. Prodeleted precursors are translocated and have their signal sequences removed, but they accumulate in the secretion apparatus. We show here that the secretion of partially active proteins is restored when the prodomain is supplied in trans as an independent peptide. The secretion rescue and maturation processing that are reconstituted by the free propeptide do not reach wild type efficiency. The results of pulse-chase experiments indicate that a rate-limiting step occurs during the intracellular transit of the rescued precursors, before Kex2p proteolytic cleavage. This delayed maturation seems to be responsible for an overall slower release of the rescued polypeptides. Propeptide and AEP were secreted in equimolar amounts by both wild type and trans complemented strains, but none could be detected in the supernatant when expressed alone. These experiments suggest that the prodomain of AEP initially acts as a crucial folding aid for the early secretory transit of the translocated precursor. They further suggest that the prodomain is also required for a second structural change of the AEP precursor during its activation. PMID- 1634542 TI - Negative thyroid hormone control of human growth hormone gene expression is mediated by 3'-untranslated/3'-flanking DNA. AB - The intact human growth hormone (hGH) gene is negatively regulated by triiodothyronine (T3) treatment in transfected rat pituitary tumor cells. We now demonstrate that this responsiveness is mediated by a negative thyroid hormone response element (nTRE) localized to the proximal 3'-untranslated/3'-flanking region (3'-UT/FR). This region binds thyroid hormone receptors specifically and with high affinity. nTRE function was promoter-dependent, since it suppressed the activity of a positive TRE in the human chorionic somatomammotropin promoter, partially repressed activity of the herpes simplex virus TK promoter, but did not function with the human actin or Rous sarcoma virus promoters. T3 treatment did not alter transcript termination sites nor selectively affect the stability of transcripts containing the hGH 3'-UT/FR when transcription was blocked by actinomycin D treatment. The function of the nTRE depended on its location in the 3'-UT/FR; it was inactive when positioned down-stream of the simian virus 40 (SV40) 3'-UT/FR, and it acted as a positive TRE when placed upstream of the hGH promoter. These results demonstrate a novel localization of a TRE with unique properties which suggests expanded mechanisms by which thyroid hormone receptors can affect gene expression. PMID- 1634543 TI - Identification of the catalytically important histidine of 3-hydroxy-3 methylglutaryl-coenzyme A reductase. AB - We identify His381 of Pseudomonas mevalonii 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase as the basic residue functional in catalysis. The catalytic domain of 20 HMG-CoA reductases contains a single conserved histidine (His381 of the P. mevalonii enzyme). Diethyl pyrocarbonate inactivated the P. mevalonii enzyme, and hydroxylamine partially restored activity. We changed His381 to alanine, lysine, asparagine, and glutamine. The mutant proteins were overexpressed, purified to homogeneity, and characterized. His381 mutant enzymes were not inactivated by diethyl pyrocarbonate. All four mutant enzymes exhibited wild-type crystal morphology and chromatographed on substrate affinity supports like wild-type enzyme. The mutant enzymes had low catalytic activity (Vmax 0.06 0.5% that of wild-type enzyme), but Km values approximated those for wild-type enzyme. For wild-type enzyme and mutant enzymes H381A, H381N, and H381Q, Km values at pH 8.1 were 0.45, 0.27, 3.7, and 0.71 mM [(R,S)-mevalonate]; 0.05, 0.03, 0.20, and 0.11 mM [coenzyme A]; 0.22, 0.14, 0.81, and 0.62 mM [NAD+]. Km values at pH 11 for wild-type enzyme and mutant enzyme H381K were 0.32 and 0.75 mM [(R,S)-mevalonate]; 0.24 and 0.50 mM [coenzyme A]; 0.15 and 1.23 mM [NAD+]. Both pK values for the enzyme-substrate complex increased relative to wild-type enzyme (by 1-2.5 pH units for pK1 and by 0.5-1.3 pH units for pK2). For mutant enzyme H381K, the pK1 of 10.2 is consistent with lysine acting as a general base at high pH. His381 of P. mevalonii HMG-CoA reductase, and consequently the histidine of the consensus Leu-Val-Lys-Ser-His-Met-Xaa-Xaa-Asn-Arg-Ser motif of the catalytic domain of eukaryotic HMG-CoA reductases, thus is the general base functional in catalysis. PMID- 1634544 TI - Myristoylation of flagellar creatine kinase in the sperm phosphocreatine shuttle is linked to its membrane association properties. AB - TCK, the flagellar creatine kinase (ATP:creatine N-phosphotransferase) of sperm from the sea urchin Strongylocentrotus purpuratus is a membrane-associated lipophilic protein involved in energy transport. The cDNA derived protein sequence contains a consensus site sufficient for the covalent attachment of myristate. To examine whether TCK was myristoylated, mouse fibroblast Swiss 3T3 and baby hamster kidney cell lines were transfected with a cDNA encoding the entire TCK protein linked to a metallothionein promotor. TCK expression was induced by zinc and paralleled by incorporation of [3H]myristic acid derived label into the protein. 3H Label incorporated into TCK was resistant to hydroxylamine treatment. The 3H-labeled material released from TCK by acid methanolysis eluted from a C18 reverse phase high pressure liquid chromatography column at the positions of myristic acid and methylmyristate. Thus, TCK expressed in transfected mammalian cell lines contains authentic myristic acid, covalently attached through amide linkage. [3H]Myristoyl TCK comigrated on two-dimensional gels with the purified lipophilic isoform TCK II from sea urchins. Furthermore, like TCK II, [3H]myristoyl TCK associated with phospholipid liposomes, suggesting that myristoylation may mediate the observed membrane association of TCK. Myristoylation of sea urchin sperm flagellar creatine kinase may play a role in confining this enzyme to the flagellum during spermatogenesis. PMID- 1634545 TI - Interaction of AP-1-, AP-2-, and Sp1-like proteins with two distinct sites in the upstream regulatory region of the plasminogen activator inhibitor-1 gene mediates the phorbol 12-myristate 13-acetate response. AB - Phorbol 12-myristate 13-acetate induces a 3- and 10-fold induction of chloramphenicol acetyltransferase (CAT) activity in HT1080 and HeLa cells, respectively, following transient transfection of a 336-base pair plasminogen activator inhibitor-1 (PAI-1) promoter fragment linked to a CAT reporter gene. Substitution mutations in the regions encompassing nucleotides -78 to -69 (TGGGTGGGGC) or -61 to -54 (TGAGTTCA), but not in the regions -155 to -149 (TGCCTCA) or -84 to -76 (AGTGAGTGG) reduced this induction. Gel electrophoresis of double-stranded -65 to -50 oligonucleotides of the PAI-1 promoter region and nuclear extracts from Hela cells produced a gel shift pattern similar to that obtained with a AP-1 consensus oligomer, and excess unlabeled AP-1 oligomer reverted binding, suggesting that this region of the PAI-1 promoter is an AP-1 like binding site. Gel electrophoresis of double-stranded -82 to -65 oligonucleotides with HeLa nuclear extracts revealed a gel shift pattern of three bands; Sp1 consensus oligomer competed with the binding to two of these bands and AP-2 consensus sequence oligomer with the binding to the third band. The -82 to 65 oligomer also bound to purified AP-2 and Sp1 proteins. Southwestern blotting of HeLa nuclear extracts revealed that the labeled oligomer spanning region -82 to -65 bound to proteins with molecular masses of 52 and 72 kDa. Consensus AP-2 oligonucleotides competed for binding of the labeled -82 to -65 oligonucleotide to the 52-kDa protein, but consensus Sp-1 oligonucleotides did not compete for binding to the 72-kDa compound. The 72-kDa component binding to the -82 to -65 region may represent a new protein involved in transcriptional regulation. PMID- 1634546 TI - Folding of human lysozyme in vivo by the formation of an alternative disulfide bond. AB - The mutant h-lysozyme, W64CC65A, with Trp64 and Cys65 replaced by Cys and Ala, respectively, was secreted by yeast and purified. Peptide mapping confirmed that W64CC65A contained a nonnative Cys64-Cys81 bond and three native disulfide bonds. The mutant had 2% of the lytic activity of the wild-type lysozyme. The midpoint concentration of the guanidine hydrochloride denaturation curve, the [D]1/2, was 2.7 M for W64CC65A at pH 3.0 and 25 degrees C, whereas the [D]1/2 for the wild type h-lysozyme was 2.9 M. These results show that the W64CC65A protein is a compactly folded molecule. Our previous results, using the mutant C81A, indicate that Cys81 is not required for correct folding and activity, whereas Cys65 is indispensable (Taniyama, Y., Yamamoto, Y., Kuroki, R., and Kikuchi, M. (1990) J. Biol. Chem. 65, 7570-7575). Cys64 substituted for Cys65 in W64CC65A, even though the distance between the alpha-carbons at positions 64 and 81 in the wild-type h lysozyme is not favorable for forming a disulfide bond. Unlike C81A, the mutant W64CC65/81A, which has the additional substitution of Ala for Cys81, did not fold. These results suggest that the absence of both the Cys64-Cys81 bond and the amino acid residue Trp64 caused the misfolding or destabilization of W64CC65/81A in vivo. It is proposed that the formation of the alternative bond, Cys64-Cys81 is important for the folding of W64CC65A in vivo. PMID- 1634547 TI - Use of fetal intestinal isografts from normal and transgenic mice to study the programming of positional information along the duodenal-to-colonic axis. AB - The four principal cellular constituents of the mouse intestinal epithelium are all derived from a multipotent stem cell functionally anchored near the base of its crypts. Differentiation of enterocytes, enteroendocrine, and goblet cells occurs during an orderly upward migration from monoclonal crypts supplied by a single active stem cell to adjacent polyclonal small intestinal villi or to their colonic homologs, the surface epithelial cuffs. Paneth cells differentiate as they descend to the base of crypts. This epithelium undergoes rapid and perpetual renewal yet is able to maintain cephalocaudal (duodenal-to-colonic) differences in the differentiation programs of its four cell types from the time of its initial cytodifferentiation in late fetal life (embryonic (E) days 16-17). Rat liver fatty acid-binding protein/human growth hormone transgenes (Fabpl/hGH) have been used as novel phenotypic markers to describe the biological properties of gut stem cells and the differentiation programs of their enterocytic and enteroendocrine lineages. To determine whether the multipotent stem cell is able to retain a "positional" address in the absence of luminal signals, we prepared isografts from the proximal small intestine or distal small intestine and colon of E15-E16 Fabpl/hGH transgenic mice and their normal littermates and implanted them into the subcutaneous tissues of young, adult male CBY/B6 nude mice. Immunocytochemical and histochemical studies indicate that appropriate position specific differences in the differentiation programs of each of the four principal cell lineages are present along the cephalocaudal and crypt-to-villus (or crypt-to-epithelial cuff) axes of isografts harvested 4-6 weeks after implantation. This suggests that the gut stem cell can be characterized not only by its multipotency and enormous capacity for self-renewal but also by its ability to be programmed (? imprinted) with positional information. Transgene expression is reduced in a number of enteroendocrine subpopulations in small intestinal and colonic isografts compared to the intact gut. Moreover, the decision to express the Fabpl/hGH transgene appears to be coordinated between adjacent crypts as evidenced by (i) the presence of multicrypt patches of wholly reporter (hGH)-positive or reporter-negative cells in the intact colon and in colonic isografts and (ii) by the presence of coherent bands of reporter-positive or -negative cells that emanate from adjacent monophenotypic crypts and extend to the apical extrusion zone of distal small intestinal villi.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1634548 TI - Localization of the C termini of the Rh (rhesus) polypeptides to the cytoplasmic face of the human erythrocyte membrane. AB - We have raised a rabbit antiserum to a synthetic peptide corresponding to the C terminus (residues 400-416) of the Rh30A polypeptide. The rabbit antiserum reacted with the Rh30B (D30) polypeptide in addition to the Rh30A (C/c and/or E/e) polypeptide(s), indicating that these proteins share homology at their C termini. The antiserum did not react with erythrocyte membranes from an individual with Rh(null) syndrome. The rabbit antiserum immunoprecipitated Rh polypeptides from erythrocyte membranes and alkali-stripped membranes, but not from intact erythrocytes. Treatment of intact red cells with carboxypeptidase Y did not affect the reactivity of the antiserum, whereas treatment of alkali stripped and unsealed erythrocyte ghost membranes resulted in the loss of antibody binding. Carboxypeptidase A treatment of intact erythrocytes and alkali stripped membranes had no effect on antibody binding, indicating that the C terminal domains of the Rh polypeptides contain lysine, arginine, proline, or histidine residues. These results show that the C termini of the Rh polypeptides are located toward the cytoplasmic face of the erythrocyte membrane. Treatment of intact radioiodinated erythrocytes with bromelain followed by immunoprecipitation with monoclonal anti-D gave a band of M(r) 24,000-25,000, indicating that the Rh30B (D30) polypeptide is cleaved at an extracellular domain close to the N or C terminus, with loss of the major radioiodinated domain. Immunoblotting of bromelain treated D-positive erythrocyte membranes with the rabbit antiserum to the C-terminal peptide revealed a new band of M(r) 6000-6500, indicating that the extracellular bromelain cleavage site is located near the C terminus of the molecule. The band of M(r) 6000-6500 was not obtained in erythrocyte membranes derived from bromelain treated D-negative erythrocytes. Erythrocytes of the rare D- phenotype appear to either totally lack, or have gross alterations in, the Cc/Ee polypeptide(s), since the bromelain treatment of these cells resulted in the total loss of staining in the M(r) 35,000-37,000 region and the concomitant appearance of the new band of M(r) 6000-6500. PMID- 1634549 TI - Lipoprotein lipase release from BFC-1 beta adipocytes. Effects of triglyceride rich lipoproteins and lipolysis products. AB - Lipoprotein lipase (LPL), synthesized by adipocytes and myocytes, must be transported to the luminal endothelial cell surface where it then interacts with circulating lipoproteins. The first step in this extracellular LPL transport pathway is LPL release from the surface of LPL-synthesizing cells. Because hydrolysis of triglyceride (TG)-rich lipoproteins releases LPL from the apical surface of endothelial cells, we hypothesized that the same substances dissociate LPL from adipocytes. 125I-LPL was bound to the surface of brown adipocytes (BFC-1 beta). LPL binding to the adipocyte surface was greater than to endothelial cell surfaces. Using low concentrations of heparin, more LPL was released from endothelial cells than BFC-1 beta, suggesting that the affinity of LPL binding to the adipocytes was greater than LPL affinity for endothelial cells. Greater than 3-fold more LPL was released from the cell surface when very low density lipoproteins (VLDL) were added to culture medium containing 3% bovine serum albumin. LPL remaining on the cell surface decreased with VLDL addition. Endogenously produced LPL activity was also released from the cells by VLDL. Low and high density lipoproteins did not release 125I-LPL or LPL activity from the adipocytes. To assess whether lipolysis was necessary for LPL release, BFC-1 beta were incubated with TG-rich lipoproteins from a patient with apoCII deficiency. The apoCII-deficient lipoproteins did not release LPL unless an exogenous source of apoCII was added. Apolipoproteins E and Cs and high molar ratios of oleic acid:bovine serum albumin did not release surface-associated LPL. Lysolecithin (25 and 100 microM), but not lecithin, monoglycerides, or diglycerides, released adipocyte surface LPL. Because lysolecithin also released LPL during a 4 degrees C incubation, cellular metabolic functions are not required for LPL dissociation from the cells. Lysolecithin also inhibited LPL binding to endothelial cells; however, this effect was abrogated by addition of bovine serum albumin. We hypothesize that lipolysis products from TG-rich lipoproteins release adipocyte surface LPL, which can then be transported to the luminal endothelial cell surface. PMID- 1634550 TI - Purification and characterization of multiple components of human lymphoblastoid interferon-alpha. AB - Twenty-two components of human interferon-alpha (IFN-alpha) derived from Sendai virus-induced Namalwa cells were purified by sequential immunoadsorbent affinity chromatography using four monoclonal antibody affinity columns followed by ultrafiltration and reversed-phase high-performance liquid chromatography. The specific activity ranged from 0.2 to 2.6 x 10(8) IU/mg protein on Madin-Darby bovine kidney cells, 0.3 to 4.6 x 10(8) IU/mg protein on human WISH cells, and 10(4) to 7 x 10(5) units/mg protein on mouse L929 cells. The apparent molecular weights of the components ranged from 17,500 to 23,300 using nonreducing sodium dodecyl polyacrylamide-gel electrophoresis and 17,500 to 27,600 using reducing sodium dodecyl polyacrylamide-gel electrophoresis. The amino-terminal amino acid sequences were similar among the components as well as to those reported for the cloned human IFN-alpha genes (Pestka, S. (1986) Methods Enzymol. 119, 3-14). However, four components, f, i, l, and m, have amino-terminal amino acid sequences which appear to be unique when compared to those predicted from the cDNA clones. One component, pre-a, has a potential N-linked glycosylation site on the Asn of residues 2 through 4, Asn-Leu-Ser. PMID- 1634551 TI - Heterologous desensitization of platelet-derived growth factor-mediated arachidonic acid release and prostaglandin synthesis. AB - Prolonged treatment of quiescent Swiss 3T3 cells with vasopressin induced heterologous desensitization of specific early signals stimulated by platelet derived growth factor (PDGF). PDGF caused a striking dose-dependent release of [3H]arachidonic acid (EC50 = 2 ng/ml) and prostaglandin E2 (EC50 = 5 ng/ml). These responses are severely attenuated (greater than 85%) by prior exposure to vasopressin in a dose-dependent manner (IC50 = 1.5 nM). Maximal loss of responsiveness occurred after 40 h of vasopressin treatment with a half-maximal desensitization after 11-13 h. The desensitization is dependent upon binding to the V1 receptor, since it can be prevented by the antagonist [Pmp1,O-Me Tyr2,Arg8]vasopressin. In contrast, stimulation of inositol phosphate accumulation and production of diacylglycerol and phosphatidic acid by PDGF are unchanged. Thus, the observed heterologous desensitization cannot be attributed to an inability to activate phospholipase C. Furthermore, prior exposure to vasopressin did not affect the ability of PDGF to evoke tyrosine phosphorylation of cellular substrates, demonstrating that vasopressin-induced heterologous desensitization causes a block at a point distal to activation of receptor tyrosine kinase activity. Other downstream responses including transient induction of c-fos expression and stimulation of DNA synthesis were attenuated by vasopressin pretreatment. The findings demonstrate a novel mechanism of heterologous cellular desensitization namely, persistent occupancy of a guanine nucleotide-binding protein-coupled receptor, like the V1 type vasopressin receptor, attenuates responsiveness to a polypeptide growth factor like PDGF that initiates responses through a tyrosine kinase receptor. PMID- 1634552 TI - Coordinate regulation of glycogen metabolism in the yeast Saccharomyces cerevisiae. Induction of glycogen branching enzyme. AB - The yeast glycogen branching enzyme (EC 2.4.1.18) is shown to be induced in batch culture simultaneously with the onset of intracellular glycogen accumulation. The branching enzyme structural gene (GLC3) has been cloned. Its predicted amino acid sequence is very similar to procaryotic branching enzymes. Northern analysis indicates that GLC3 mRNA abundance increases in late exponential growth phase coincident with glycogen accumulation. Disruption of the branching enzyme structural gene establishes that branching enzyme activity is an absolute requirement for maximal glycogen synthesis. PMID- 1634553 TI - Identification of the type 2 proinsulin processing endopeptidase as PC2, a member of the eukaryote subtilisin family. AB - Enzymological studies have implicated two Ca(2+)-dependent endopeptidases in the conversion of proinsulin to insulin; a type 1 activity which cleaves on the C terminal side of Arg31-Arg32 and a type 2 activity which cleaves C-terminally to Lys64-Arg65 in the proinsulin sequence. The possibility that these enzymes are related to the recently discovered family of mammalian subtilisin-like gene products (furin, PC2, and PC3) and the yeast propheromone-converting enzyme (KEX 2), was investigated. Degenerate oligonucleotide primers flanking the putative catalytic domain within this gene family were used in a polymerase chain reaction to amplify related sequences from rat insulinoma cDNA. One major product of 700 base pairs was obtained which was greater than 99% identical to the corresponding rat PC2 sequence. This cDNA was subcloned into the bacterial expression vector pGEX-3X to generate a recombinant protein for antibody production. Western blot analysis showed the immunoreactivity was prominent in neuroendocrine tissues as a 65-kDa protein. It was concentrated in secretory granule-enriched fractions of insulinoma tissue, where it was present as a readily solubilized monomeric protein. Deglycosylation studies using endoglycosidase H and N-glycanase showed that the 65-kDa protein was comprised of approximately 9% carbohydrate, consistent with the presence of three consensus sequences for N-linked glycosylation in rat PC2. The immunoreactivity co-eluted with the type 2 proinsulin endopeptidase on gel filtration and ion-exchange chromatography and the antisera specifically immunoprecipitated type 2 activity from insulin granule extracts. N-terminal sequence analysis of the immunoreactive protein gave two sequences which corresponded to residues 109-112 and 112-119 of rat PC2. This indicated that posttranslational processing of PC2 itself occurs C-terminally to basic amino acids to produce the mature enzyme. It is concluded that PC2 is the type 2 endopeptidase involved in proinsulin conversion. Localization of PC2 immunoreactivity to other tissues of the diffuse neuroendocrine system suggests that the type 2 endopeptidase also functions in the processing of precursor forms of other prohormones and polypeptide neurotransmitters. PMID- 1634554 TI - Sphingosine activation of protein kinases in Jurkat T cells. In vitro phosphorylation of endogenous protein substrates and specificity of action. AB - Sphingosine displays multiple biochemical and biological effects, in particular inhibition and activation of protein kinases. To determine the predominant interaction of sphingosine with cellular kinases, the effects of sphingosine on endogenous protein phosphorylation in Jurkat T lymphoblastic cells were investigated in vitro. Sphingosine was found to cause prominent phosphorylation of a number of cytosolic proteins ranging in molecular mass from 18 to 165 kDa. Phosphorylation was calcium-independent. Phosphorylation of substrates was increased in response to concentrations of sphingosine as low as 10 microM and peaked at concentrations of 20-200 microM. Multiple lines of evidence suggested that sphingosine activated more than one protein kinase: 1) the concentration dependence on sphingosine differed from substrate to substrate, 2) phosphorylation of one group of substrates required ATP as the phosphate donor, whereas a second group showed no preference between ATP and GTP, and 3) phosphorylation of some substrates was inhibited by heparin, whereas other substrates were resistant. Activation of these kinases demonstrated a very specific requirement for D-erythro-sphingoid bases. DL-erythro-dihydrosphingosine was partially active, whereas DL-threo-dihydrosphingosine was not. Other related molecules such as stearylamine, sphingomyelin, and C2-ceramide were not active. Sphingosine-activated kinase(s) were distinct from protein kinase C, cyclic nucleotide-activated kinases, and calcium-dependent kinases. These observations demonstrate the existence of multiple sphingosine-activated protein kinases with high specificity for D-erythro-sphingosine, suggesting physiologic regulation of protein phosphorylation by sphingosine. PMID- 1634555 TI - A novel human insulinoma-associated cDNA, IA-1, encodes a protein with "zinc finger" DNA-binding motifs. AB - A subtraction library was constructed from human insulinoma (beta cell tumor) and glucagonoma (alpha cell tumor) cDNA phagemid libraries. Differential screening of 153 clones with end-labeled mRNAs from insulinoma, glucagonoma, and HeLa cells resulted in the isolation of a novel cDNA clone designated IA-1. This cDNA clone has a 2838-base pair sequence consisting of an open reading frame of 1530 nucleotides, which translates into a protein of 510 amino acids with a pI value of 9.1 and a molecular mass of 52,923 daltons. At the 3'-untranslated region there are seven ATTTA sequences between two polyadenylation signals (AATAAA). The IA-1 protein can be divided into two domains based upon the features of its amino acid sequence. The NH2-terminal domain of the deduced protein sequence (amino acids 1-250) has four classical pro-hormone dibasic conversion sites and an amidation signal sequence, Pro-Gly-Lys-Arg. The COOH-terminal domain (amino acids 251-510) contains five putative "zinc-finger" DNA-binding motifs of the form X3 Cys-X2-4-Cys-X12-His-X3-4-His-X4 which has been described as a consensus sequence for members of the Cys2-His2 DNA-binding protein class. Northern blot analysis revealed IA-1 mRNA in five of five human insulinoma and three of three murine insulinoma cell lines. Expression of this gene was undetectable in normal tissues. Additional tissue studies revealed that the message is expressed in several tumor cell lines of neuroendocrine origin including pheochromocytoma, medullary thyroid carcinoma, insulinoma, pituitary tumor, and small cell lung carcinoma. The restricted tissue distribution and unique sequence motifs suggest that this novel cDNA clone may encode a protein associated with the transformation of neuroendocrine cells. PMID- 1634556 TI - Proceedings of the workshop on methodology and protocol of human fertility studies under field conditions. June 1991. PMID- 1634557 TI - Human fertility studies under field conditions. Introduction. PMID- 1634558 TI - The female reproductive axis and its modifications during the post-partum period. PMID- 1634559 TI - Aetiological approach of female reproductive physiology in lactational amenorrhoea. PMID- 1634560 TI - Breast-feeding patterns, maternal milk output and lactational infecundity. PMID- 1634561 TI - The assessment of total energy expenditure of female farmers under field conditions. AB - The paper reviews methods, and their difficulties, in the measurement of the daily energy expenditure of rural women under field conditions in developing countries. Since all methods need to be validated against a reference method which is usually based on indirect calorimetry, examples of the use of this technique are given. The energy costs of most agricultural and daily tasks of rural women in developing countries have been measured. Large intra- and inter individual variations in the cost of a single activity occur, so repeated measurements are needed to obtain a valid mean energy cost for a specific activity for a homogeneous group of individuals. Much work remains to be done on the assessment of the duration and the intensity of the physical activity of the rural adolescent and adult female population. Studies indicate that the workload of most rural women in developing countries is excessive and frequently associated with acute poverty. PMID- 1634562 TI - Estimating energy and nutrient intakes in studies of human fertility. AB - Two methods of dietary recording, the 24-hr recall and the weighed dietary intake methods, are considered appropriate for estimating energy and nutrient intakes in studies of human fertility. The former method gives lower estimates than the latter, although weighed intakes may underestimate true intakes. Examination of food intakes of pregnant, lactating, and non-pregnant, non-lactating New Guinean women shows their diet to be less homogeneous than is generally assumed for groups in developing countries. As a result direct observations of food intake for a limited number of days are not sufficiently accurate for the estimation of intake of most of the nutrients examined. Rather the study design should reflect the variability of intakes of the nutrients and groups under consideration. PMID- 1634563 TI - Estimates of metabolic adaptation in women living in developing countries: technical limitations. AB - The measurement of food intake has long been used to describe 'adaptation' to low energy intakes in certain tropical peoples. However, the methods available to quantify food intake are unlikely to reflect accurately real energy intakes in free living peoples. Alternatively, estimating energy expenditure shows some promise--particularly the measurement of basal metabolic rate (BMR). The BMR may be measured effectively in males, but females show wide intra-individual variation in BMR during their menstrual cycle, which makes BMR measurements more difficult to interpret in the context of adaptation. The use of double-labelled water may be the only method suitable to quantify and define 'adaptation' to low intakes in women. PMID- 1634564 TI - Endemic disease, nutrition and fertility in developing countries. PMID- 1634565 TI - Maternal body composition: methods for measuring short-term changes. AB - The measurement of short-term changes in maternal body composition during the post-partum period under field conditions poses many problems: (1) body composition techniques depend on the constancy of the proportions of components or their physical properties and are less suitable for measuring changes; (2) many of the techniques require expensive, technically sophisticated apparatus that is inappropriate to field conditions in many countries; (3) changes in body composition affect some areas of the body more than others so regional as well as whole body approaches are required. The measurements of body weight, triceps and subscapular skinfold thicknesses and upper arm circumference are essential measurements. These can be supplemented with further skinfold thicknesses and circumferences, and possibly body density and body water measurements. There is little to be gained by transforming anthropometric variables into whole body composition indices in these circumstances. PMID- 1634566 TI - Brief description of WHO protocol for data collection. PMID- 1634567 TI - Round table discussion on research design, statistical aspects and data collection. PMID- 1634568 TI - The ecology of birth seasonality among agriculturalists in central Africa. AB - The Lese are subsistence farmers living in the Ituri Forest of north-east Zaire. They exhibit significant birth seasonality, with lowest frequencies of conception when food production is least, nutritional status is low and ovarian function, as measured by salivary steroid hormone levels, is reduced. Efe pygmy foragers, who live in the same geographical area but are less dependent on cultivated foods and have a more flexible life style, do not exhibit frequent fluctuations in nutritional status nor significant birth seasonality. These findings support a model of birth seasonality relating climatic variables to variation in fertility through a causal chain linking rainfall to food production to energy balance to ovarian function to fertility. The model, which emphasises an ecological approach to the study of human reproduction, should have broad applicability since seasonality of food production and energy balance is widespread geographically and across a wide variety of economies and cultures. PMID- 1634569 TI - Studies on perceived breast-milk insufficiency: relation to attitude and practice. AB - Fifty-one mother-infant pairs were followed prospectively by home visits and telephone contacts during the first 6 months post-partum. Comparisons between mothers who experienced lactation crises because of perceived breast-milk insufficiency (crisis group) and those who did not (non-crisis group) revealed differences in attitudes to breast-feeding, breast-feeding behaviour and sexual life. The crisis group tended to initiate breast-feeding for infant-related reasons more frequently than the non-crisis group, which more frequently gave mother-related reasons. During the course of breast-feeding attitude changes in a negative direction were significantly more common in the crisis group. No difference was found between the groups in the resumption of sexual life, but 59% of all the women claimed that they experienced less or no desire compared to before pregnancy and, of these, a significantly higher proportion belonged to the crisis group. PMID- 1634570 TI - Fixation with a single screw for slipped capital femoral epiphysis. AB - The effectiveness of a single 6.5 or seven-millimeter-diameter screw for the promotion of premature physeal closure and the provision of stability of a slipped capital femoral epiphysis was investigated. Physeal fusion was demonstrated in forty-nine (92 per cent) of fifty-three hips after fixation with a single screw. Premature fusion of the involved physis, compared with the uninvolved, contralateral physis, was documented (p less than 0.001). Epiphyseal stability, as measured by the lateral head-shaft angle, was maintained in all except one hip. An analysis of twenty-nine hips for which there was a complete set of radiographs, that were in patients who had no endocrine problems, and that were the first hips entered into the study when the patient had bilateral involvement, revealed an average time to closure of the physeal line of thirteen months. A longer time to physeal fusion was correlated with increasingly eccentric placement of the screw (r = 0.44, p = 0.016) and increasing severity of the slip (r = -0.536, p = 0.003). There was no correlation between the age at the time of the operation, race, or sex and the time to physeal fusion. Only one patient had penetration by a screw, and no chondrolysis, avascular necrosis, or other serious problems developed. Fixation with a single 6.5 or seven-millimeter diameter screw provided adequate epiphyseal stability and promoted premature physeal fusion in our patients, while decreasing the rate of complications compared with that reported to be associated with fixation with multiple screws or pins. PMID- 1634571 TI - Slipped capital femoral epiphysis. A prospective study of fixation with a single screw. AB - Forty-four children (fifty-eight hips) who had a slipped capital femoral epiphysis were managed by in situ pinning with a single cannulated screw. This method of treatment was first used in our institution in 1983. Thirty-one boys and thirteen girls were followed for an average of three years (range, two to six years). There were eight acute slips and fifty chronic slips. Thirty-four patients were black and ten patients were white. The clinical criteria of Heyman and Herndon and the radiographic parameters cited by Boyer et al. were used to grade the results. Fifty-four hips were rated as either excellent or good. Avascular necrosis developed in one patient who had an acute slipped capital femoral epiphysis, but chondrolysis did not occur in any patient. The complications included a subtrochanteric fracture in one patient and an increase in the degree of slippage of the capital femoral epiphysis in two patients. PMID- 1634572 TI - Clinical determination of femoral anteversion. A comparison with established techniques. AB - We evaluated femoral anteversion preoperatively in fifty-nine patients (ninety one hips), using a clinical method that we developed, Magilligan radiographs, and computed tomographic scans. These measurements were then compared with values for anteversion that were obtained intraoperatively. To determine femoral anteversion clinically, the patient was placed in the prone position and the maximum lateral trochanteric prominence was related to the degree of internal rotation of the hip. Compared with computed tomographic scanning and Magilligan radiographic determination, the clinically determined anteversion correlated most closely (to within 4 degrees) with the amount measured at the time of the operation. The clinical method was found to be superior to radiographic techniques for determination of the degree of femoral anteversion in children who have not had a previous operation about the hip. PMID- 1634573 TI - Residual chymopapain activity after chemonucleolysis in normal intervertebral discs in dogs. AB - Studies were carried out to demonstrate residual chymopapain activity in intervertebral discs after chemonucleolysis; protease assay, enzyme-linked immunosorbent assay, and immunohistochemical localization of the chymopapain in the disc tissue were done. Chymopapain, one milligram per level, was injected into the normal lumbar intervertebral discs of adult mongrel dogs and the discs were excised after two weeks. Proteolytically active chymopapain was still present in the extract of intervertebral disc at this time. The proteolytic activity was decreased by sulfhydryl inhibitors but not by inhibitors of metalloproteases or serine proteases. Protease and enzyme-linked immunosorbent assays showed that 0.60 +/- 0.48 per cent and 0.49 +/- 0.38 per cent of the original dose was present two weeks after the injection. Chymopapain was shown by immunohistochemical staining to be diffusely located throughout the extracellular matrix of the anulus fibrosus and the nucleus pulposus. Some cells, located mainly in the inner portion of the anulus, contained vacuoles filled with immunoreactive product. PMID- 1634574 TI - The effect of femoral stem geometry on interface motion in uncemented porous coated total hip prostheses. Comparison of straight-stem and curved-stem designs. AB - We compared the magnitudes of motion between the prosthesis and bone during axial and torsional loading in seven matched pairs of fresh-frozen femora of cadavera in which an uncemented, collarless, isthmus-filling, straight-stem (Harris Galante) prosthesis had been placed in one femur and an uncemented, collarless, proximal-filling, curved-stem (anatomic) prosthesis had been placed in the other femur. The comparison was performed in order to determine the effect of the geometry of the stem on the magnitude of motion. Single-limb-stance loads and combined axial and torsional loads were applied to the implanted femoral prostheses with the use of a jig that simulated acetabular and trochanteric loading. Extensometers were used to measure motion at the prosthesis-bone interface. The prostheses were then removed and were reinserted, with cement applied to the proximal porous coating to simulate ingrowth of bone. The single limb-stance and combined axial and torsional loads were reapplied and the magnitude of motion was recorded again. No significant differences in the magnitudes of the motion were found between the femora in which the straight stem had been implanted and the femora in which the curved stem had been implanted, during either simulated single-limb-stance or low-intensity torsional loading. When large torsional moments (twenty-two newton-meters) were applied, significantly less motion occurred at the bone-prosthesis interface, both proximally (p = 0.019) and distally (p = 0.0013), in the femora with the curved stem implant than in the femora with the straight-stem implant. When cement had been applied proximally, proximal and distal motion between the prosthesis and the femur was decreased during simulated single-limb-stance and during torsional loading in the femora with the straight stem and the femora with the curved stem. PMID- 1634575 TI - Periprosthetic bone loss in total hip arthroplasty. Polyethylene wear debris and the concept of the effective joint space. AB - Thirty-four hips in which there had been prosthetic replacement were selected for study because of the presence of linear (diffuse) or lytic (localized) areas of periprosthetic bone loss. In all hips, there was careful documentation of the anatomical location of the material that had been obtained for histological analysis, and the specific purpose of the removal of the tissue was for examination to determine the cause of the resorption of bone. Specimens from twenty-three hips were retrieved during an operation and from eleven hips, at autopsy. The area of bone loss was linear only in sixteen hips, lytic only in thirteen, and both linear and lytic in five. In all thirty-four hips, intracellular particulate debris was found in the macrophages that were present in the area of bone resorption. All thirty-four had intracellular particles of polyethylene, many of which were less than one micrometer in size. Thirty-one hips had extracellular particles of polyethylene as well. Twenty-two of the thirty-four hips had intracellular metallic debris; in ten, metallic debris was found extracellularly as well. Ten of the sixteen cemented specimens had intracellular and extracellular polymethylmethacrylate debris. In the mechanically stable prostheses--cemented and uncemented--polyethylene wear debris was identified in areas of bone resorption far from the articular surfaces. The number of macrophages in a microscopic field was directly related to the amount of particulate polyethylene debris that was visible by light microscopy. Although the gross radiographic appearances of linear bone loss and lytic bone loss were different, the histological appearance of the regions in which there was active bone resorption was similar. Regardless of the radiographic appearance and anatomical origin of the specimen, bone resorption was found to occur in association with macrophages that were laden with polyethylene debris. In general, the number of macrophages present had a direct relationship to the degree of bone resorption that was seen. We believe that these findings indicate that joint fluid penetrates far more extensively than previously thought, even in a well fixed component, along the interface between the prosthesis and bone and in the periprosthetic tissues; it is often more extensive than is shown by arthrography. We therefore suggest the concept of the effective joint space to include all periprosthetic regions that are accessible to joint fluid and thus accessible to particulate debris.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1634576 TI - Osteolysis after total knee arthroplasty without cement. AB - The prevalence and characteristics of osteolysis were studied after 174 consecutive total knee arthroplasties, performed without cement; 16 per cent (twenty-seven) of the implants (in twenty-six patients) were identified as being associated with osteolysis. The diagnosis was made an average of thirty-five months after the operation. Fifteen (56 per cent) of the twenty-seven prostheses were revised after an average of forty-five months in situ. The remaining twelve implants were still in situ five years or more postoperatively. In the patients who were managed with revision, six implants were judged to be stable radiographically and intraoperatively. The remaining nine implants were loose. The average age of the patients who had osteolysis was sixty-three years, and the average weight was seventy-six kilograms (168 pounds). Eighteen of the twenty-six patients who had osteolysis were women. The medial aspect of the tibial metaphysis was the most common site for resorption of bone (twenty-four knees). Sequential radiographs demonstrated progressive extension of the osteolytic process around the tibial base-plate of the prosthesis and distally into the tibial metaphysis along the screw-bone interface in all patients. Histological evaluation of tissue obtained at the revision procedures revealed sheets of histiocytes and occasional giant cells. Intracellular particulate polyethylene and metal were found; most particles were less than one micrometer in size, although particles as large as three micrometers were identified. Mechanical failure of the thin, modular, polyethylene tibial insert; excessive abrasion of the prominent polyethylene tibial eminence, with secondary wear and impingement of the pin on the femoral component; and failure of the metal-backed patellar component all contributed to the extensive amount of polyethylene and the variable amount of metal debris that were generated. Corrosion between the angulated titanium screws and the cobalt-chromium base-plate also contributed particulate metal to the osteolytic process locally. This study demonstrated that osteolysis occurs in association with cementless total knee replacement. PMID- 1634577 TI - Unicompartmental knee replacement: a comparison of constrained and unconstrained designs. AB - Seventy-six patients who had eighty-seven unicompartmental knee replacements were followed for an average of fifty-three months (range, two to twelve years). The operation was on the medial side in eighty-two knees and on the lateral side in five. Fifty replacements were unconstrained and thirty-seven were constrained. Of the fifty knees that had an unconstrained replacement, forty-nine (98 per cent) had a good or excellent result, compared with only twenty-six (70 per cent) of the knees that had a constrained replacement; the difference is significant (p = 0.0007). No knee that had an unconstrained replacement had a poor result, compared with nine (24 per cent) of the knees that had a constrained replacement (p = 0.0009). Four (8 per cent) of the fifty knees that had an unconstrained replacement later had a revision total knee arthroplasty, compared with ten (27 per cent) of the thirty-seven knees that had a constrained replacement; the difference is significant (p = 0.04). Noteworthy degenerative changes in the opposite compartment occurred in only one of the eighty-seven knees (a knee in which an unconstrained prosthesis had been inserted). PMID- 1634578 TI - Modular hemiarthroplasty for fractures of the proximal part of the humerus. AB - A new biomodular prosthesis was used for the treatment of a displaced fracture of the proximal part of the humerus in twenty-two shoulders in twenty-two patients. The fractures were classified according to the Neer system; there were thirteen four-part, five three-part, and four head-splitting fractures. There were fifteen women and seven men, and the mean age was seventy years (range, forty-nine to eighty-seven years). The hemiarthroplasty was performed an average of eleven days (range, one to forty-five days) after the injury. The deltopectoral interval was used in all patients, and the prosthesis was implanted with cement in twenty of the shoulders. All of the patients participated in a supervised program of rehabilitation. The patients were followed for an average of thirty-six months (range, twenty-six to forty-nine months). Twenty of the twenty-two patients had a good or excellent result. The active forward elevation averaged 119 degrees; external rotation, 40 degrees; and internal rotation, to the twelfth thoracic vertebra. All of the patients except for the two who had a poor result had satisfactory relief of pain. The two patients who had a poor result had a successful revision with a modular prosthesis of the same design. The modular head could be removed, enabling the surgeon to gain access to the glenoid and to adjust the soft tissues. The over-all scores correlated inversely with the age of the patients and the interval from the injury to the operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634579 TI - Treatment of instability of the shoulder with an exercise program. AB - One hundred and forty shoulders in 115 patients that had a diagnosis of traumatic or atraumatic recurrent anterior, posterior, or multidirectional subluxation were treated with a specific set of muscle-strengthening exercises. Only twelve (16 per cent) of the seventy-four shoulders (sixty-eight patients) that had traumatic subluxation had a good or excellent result from the exercises, compared with fifty-three (80 per cent) of the sixty-six shoulders that had atraumatic subluxation. For this reason, each patient who has instability of the shoulder should be thoroughly evaluated if a successful result from conservative treatment is to be expected. Every effort must be made to identify the etiology of the instability through careful history-taking, physical examination, and radiographic evaluation. PMID- 1634580 TI - Comparison of orthoroentgenography and computed tomography in the measurement of limb-length discrepancy. AB - To determine the most accurate roentgenographic technique for the measurement of limb-length discrepancy, the twenty lower extremities of ten cadavera were measured with use of both orthoroentgenograms and lateral scout computed tomographic scanograms. The actual anatomical limb length also was measured, to serve as a control. The effects of flexion of the knee joint, use of an external fixator, cost and time of the examination, and exposure to radiation also were determined. No statistically significant difference in the measurements of the length of the femur was found between the two methods at neutral or at 15, 30, or 45 degrees of flexion of the knee. However, computed tomography was significantly more accurate than orthoroentgenography in the measurements of length of the tibia and of total length of the limb when the knee was flexed to 30 degrees or more (p less than 0.01). The placement of an Ilizarov fixator did not alter the results. The cost and time necessary to complete an examination were comparable for the two methods. However, computed tomography delivered only 20 per cent of the radiation needed for orthoroentgenography. Computed tomography is more accurate than orthoroentgenography for the measurement of limb-length discrepancy in patients who have a flexion deformity of the knee. PMID- 1634581 TI - Arthrodesis of the ankle in patients who have rheumatoid arthritis. AB - We reviewed thirty-two arthrodeses of the ankle in twenty-six patients who had rheumatoid arthritis. In seventeen patients (eighteen ankles), a compression arthrodesis was done and external fixation was used. In eight patients (twelve ankles), we used internal fixation with 6.5-millimeter cancellous-bone screws. In the remaining patient, an arthrodesis with external fixation was done in one ankle and internal fixation was used in the other ankle; data for the appropriate ankle are included in each group. The patients were followed for an average of thirty-three months. The two groups were comparable with respect to age, sex, preoperative medications, and severity of disease. The average time to fusion was nineteen weeks in the compression arthrodesis group and seventeen weeks in the internal fixation group. Of the nineteen ankles that had a compression arthrodesis, four failed to fuse; all of the failures were associated with infection. Infection developed in two additional patients, there was malposition of the fusion in three patients, and neurapraxia developed in three patients. Of the thirteen ankles that had internal fixation, three ankles failed to fuse; one of the failures was associated with infection. Infection developed in one additional ankle. In two patients, the ankle fused in excessive valgus. Comparison of the two groups revealed comparable rates of fusion: fusion occurred in fifteen of the nineteen ankles in the group that had compression arthrodesis and in ten of the thirteen ankles in the group that had internal fixation. The method of arthrodesis did not affect the time to fusion or the rate of complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634582 TI - Reflex sympathetic dystrophy in children. Clinical characteristics and follow-up of seventy patients. AB - We report on the experience with our first seventy patients who had reflex sympathetic dystrophy and were less than eighteen years old (average age, 12.5 years). In our series, the patients were predominantly girls (male to female ratio, 11:59) and the lower extremity was involved most often (sixty-one of the seventy patients). The average time from the initial injury to the diagnosis was one year, which indicates that the syndrome remains under-recognized in patients in this age-group. Conservative treatment with physical therapy, transcutaneous electrical nerve stimulation, psychological therapies including cognitive behavioral management and relaxation training, and tricyclic anti-depressants was effective in improving the average scores for pain and function for forty patients. Sympathetic blocks were helpful for twenty-eight of thirty-seven patients. Thirty-eight of the seventy patients in the series continued to have some degree of residual pain and dysfunction. Reflex sympathetic dystrophy in children differs in presentation and clinical course from the syndrome in adults. It is best treated in a multidisciplinary fashion. PMID- 1634583 TI - The effect of low-frequency electrical fields on osteogenesis. AB - An in vivo animal model of disuse osteopenia was used to determine the osteogenic potential of specific components of electrical fields. The ability of a complex pulsed electrical field to inhibit loss of bone was compared with the remodeling response generated by extremely low-power, low-frequency (fifteen, seventy-five, and 150-hertz) sinusoidal electrical fields. The left ulnae of thirty adult male turkeys were functionally isolated by creation of distal and proximal epiphyseal osteotomies and then were exposed, for one hour each day, to an electrical field that had been induced exogenously by means of magnetic induction. After a fifty six-day protocol, the remodeling response was quantified by a comparison of the cross-sectional area of the mid-part of the diaphysis of the functionally isolated ulna with that of the intact contralateral ulna. Disuse resulted in a 13 per cent mean loss of osseous tissue, which was not significantly different than the 10 per cent loss that was caused by disuse treated with inactive coils. Exposure to the pulsed electrical fields prevented this osteopenia and stimulated a 10 per cent mean increase in the bone area. The osteogenic influence of the sinusoidal electrical fields was strongly dependent on the frequency; the 150, seventy-five, and fifteen-hertz sinusoidal fields, respectively, generated a -3 per cent, + 5 per cent, and + 20 per cent mean change in the bone area. These results suggest a tissue sensitivity that is specific to very low-frequency sinusoidal electrical fields, and they imply that the induced electrical fields need not have complex waveforms to be osteogenic. Since the frequency and intensity range of the sinusoidal fields producing the greatest osteogenic response are similar to the levels produced intrinsically by normal functional activity, these results support the hypothesis that electricity plays a role in the retention of the normal remodeling balance within mature bone. PMID- 1634584 TI - Recurrent giant-cell tumor with metaplasia and malignant change, not associated with radiotherapy. A case report. PMID- 1634585 TI - Pseudotumor of the distal part of the femur in a patient who had myelomeningocele. A case report. PMID- 1634586 TI - The response to bone allografts. PMID- 1634587 TI - Reconstruction of malunited fractures of the lateral malleolus. PMID- 1634588 TI - Simple bone cysts of the pelvis in adolescents. A report of four cases. PMID- 1634589 TI - Pigmented villonodular synovitis of the knee. The results of total arthroscopic synovectomy, partial arthroscopic synovectomy, and arthroscopic local excision. PMID- 1634590 TI - Annotation: historical research in child and adolescent psychiatry: scope, methods and application. PMID- 1634591 TI - The Emanuel Miller Memorial Lecture 1991. Autism and autistic-like conditions: subclasses among disorders of empathy. AB - Recent autism and autism-related research from Gothenburg is surveyed. In indigenous families, typical autism seems no more common now than 10 years ago. Genetic factors play a part in causing autism and Asperger syndrome. Certain medical syndromes carry a relatively high risk of concomitant autistic symptoms. Evidence for non-specific brain dysfunction is often found in autism and autistic like conditions. The search for the underlying clue to the riddle of autism may be futile. Autism might be best conceptualized as a behavioural syndrome reflecting underlying brain dysfunction which shades into other clinical syndromes. A new class of disorders of empathy is proposed. PMID- 1634592 TI - Unfamiliar face recognition in relatively able autistic children. AB - Two experiments were carried out assessing autistic children's recognition, discrimination, and fixation of unfamiliar faces and unfamiliar buildings. The experiments showed that (i) unfamiliar face recognition is impaired relative to normal peers, non-verbal ability matched and verbal ability matched controls. Relative to verbal ability matched controls (ii) recognition of buildings is normal; (iii) there is an enhanced discrepancy between face discrimination and buildings discrimination, in favour of buildings; and (iv) fixation is normal. Analysis of the results suggests that impaired face recognition does not result from impaired attention or discrimination. PMID- 1634593 TI - Do young calendrical calculators improve with age? AB - The calendrical calculation performance of two 10-year-old children of the same intelligence level (IQ 90) but different calendrical ability, was compared with the performance of eight adult idiot-savant calculators. The calculating speeds of the two 10-year olds fell within the range of the reaction times of the adult savants. No improvement was detectable in a series of successive trials over time, either in speed or accuracy. It is concluded that the young calculators have already inferred rules about calendrical structure and that their performance cannot be accounted for by practice alone, but these savants use cognitive strategies to aid their performance. PMID- 1634594 TI - The relationship between digit sucking and behaviour problems: a longitudinal study over 10 years. AB - Data from the Dunedin (New Zealand) Multidisciplinary Health and Development Study were used to examine continuity and discontinuity in digit sucking between 5 and 11 years. The data were also used to examine the relationship between digit sucking and behaviour problems at 5, 7, 9, 11 and 15 years. Cross-sectional analyses showed a relationship between digit sucking and behaviour problems at all ages, except 5 years. Longitudinal analysis by multiple regression showed that digit sucking at 5 and 7 years predicted behaviour problems at 7, 9 and 11 years. This effect was most apparent at 7 years. Children who sucked their digits at 11 years were more likely to have overjets of 6mm or more between their upper and lower dental arches. The behavioural and dental evidence suggest that it would be better for children to stop sucking their digits before they started school and acquired their permanent dentition. PMID- 1634595 TI - Rates of Obsessive Compulsive Disorder in first degree relatives of patients with trichotillomania: a research note. AB - To explore a possible relationship between trichotillomania, (TTM) (compulsive hair pulling) and Obsessive Compulsive Disorder (OCD), 65 out of 69 (94%) first degree relatives of 16 female probands with severe chronic TTM were compared with two control groups for OCD and for TTM. Three (19%) of the 16 TTM probands had at least one first degree relative with a lifetime history of OCD, and there was an age corrected rate of 6.4% of first degree relatives with OCD. No relative in control group (A) met criteria for OCD. There was a trend (Fishers exact p = .07, two tailed) for a higher rate (age corrected) of OCD in TTM families; these pilot data are consistent with the concept of a spectrum of obsessive compulsive disorders which includes TTM and other pathological grooming behaviours. PMID- 1634596 TI - Patterns of psychiatric disorder in adopted girls: a research note. AB - Over a 15-year period adopted children were overrepresented in a psychiatric clinic population. The excess was seen in all age groups and there was no rise of referrals of adoptees during adolescence. Adopted boys showed the same range of disorder as all referred boys. Adopted girls were more likely than other girls to have conduct disorders. Those with conduct disorders were more likely than non adopted girls with the same disorder to be taken into care and to be given inpatient treatment. Differences in family structure and relationships were found both between conduct disordered girls of different adoptive status and between adopted girls with conduct and other disorders. PMID- 1634597 TI - Maternal predictors of behavioral disturbance in preschool children: a research note. AB - The effects of maternal mental health and familial stress on child behavior were evaluated in a community sample of 691 preschoolers. Presence of behavior problems was determined using the Behavior Screening Questionnaire (BSQ) at age 3, and using the Conners Parent Rating Scale at age 4. In multivariate analyses, the development of disturbance was predicted by higher BSQ score, maternal role competition and maternal hostility assessed at both interviews; persistence was predicted by initial BSQ score and initial maternal hostility only. These results underscore the complexity of the relationships among maternal, familial and childhood variables. PMID- 1634598 TI - Detection of pea seedborne mosaic potyvirus by sequence specific enzymatic amplification. AB - The polymerase chain reaction (PCR) was used to detect pea seedborne mosaic potyvirus (PSbMV) pathotype P1 RNA after reverse transcription of total nucleic acid preparations from pea (Pisum sativum) tissues. Tissues assayed for PSbMV included leaves, roots, petals, seed parts, and pollen. Three oligonucleotide primers in appropriate combination yielded two products of the predicted size: 730 and 1200 bp. The described methodology allows for rapid pathotype-specific PSbMV detection with utmost sensitivity and wide applicability. PMID- 1634599 TI - Direct sequence analysis of amplified dengue virus genomic RNA from cultured cells, mosquitoes and mouse brain. AB - A method is described for direct sequence analysis of selected regions of dengue virus genomic RNA in infected tissues. Using specific primers, total high molecular-weight infected-cell RNA is reverse transcribed to single-stranded (ss) complementary DNA, amplified using the polymerase chain reaction (PCR) and sequenced using ssDNA obtained after lambda exonuclease digestion of one strand of the PCR product (R.G. Higuchi and H. Ochman, Nucleic Acids Research, 17, 5865, 1989). Sequence data for the envelope protein gene of two dengue-3 virus isolates were obtained using RNA from small numbers (10(5)) of cultured mosquito or monkey kidney cells, from one mg of infected mouse brain and from 1/300th of an infected Toxorhynchites amboinensis mosquito. Independent determinations showed that errors occurring during reverse transcription or PCR were not represented to a significant degree in the sequence of the amplified DNA. The method does not depend on extensive passaging of virus or large-scale growth to generate material for sequencing and therefore provides a means of obtaining sequence data for unadapted dengue virus isolates. PMID- 1634600 TI - Rapid diagnosis of influenza A. Comparison with ELISA immunocapture and culture. AB - The Directigen Flu-A is an enzyme immunoassay for detecting in 15 min the influenza A nucleoproteinic antigen directly from specimens after passive adsorption on a cellulose membrane. The test was assessed using 160 frozen (-20 degrees C) specimens collected during the 1988-1989 A/H1N1 influenza epidemic and the 1989-1990 A/H3N2 epidemic. Compared to the ELISA immunocapture test, the sensitivity of the commercial test was 87.8% and the specificity was 97.6%. When compared to isolation of viruses on LLCMK2 cells and/or chicken embryo, the sensitivity was 84%. No cross-reaction was found with other respiratory disease viruses. The feasibility, practicability and rapidity of the test make it a test of choice for rapid diagnosis of influenza A. PMID- 1634601 TI - Development and application of protein G antibody assay for the detection of antibody to hantavirus. AB - A new serodiagnostic method designated protein-G antibody assay (PGA) was developed for detection of hantavirus infection in various species of animals. The assay procedure includes reacting the sera with hantavirus-infected cells on glass slides, followed by incubation of biotinylated protein G and amplification with the avidin-biotinylated peroxidase complex. Specific antibody in rabbit, rat, mouse and Mongolian gerbil serum was detected by this method. The PGA titres were similar to those of the neutralization titre. In the sera of Mongolian gerbils infected with strain SR-11, antibody was first detected 10 days post infection, and the titre increased to 1:256 at 18 days post-infection. PGA was evaluated using sera of urban rats (Rattus norvegicus) captured in an endemic area of hantavirus infection. The negative (much less than 1:1, 24/62, 38.7%) and positive groups (much greater than 1:16, 38/62, 61.3%) were clearly distinguished. PGA titres were closely related to IFA titres in the sera. Two of 10 sera from Clethrionomys rufocanus and one from Apodemus speciosus captured in the same endemic area were positive to both PGA and IFA. These data indicate that PGA is a simple and useful method for seroepizootiological surveys of hantavirus infection, especially in wild rodent reservoirs. PMID- 1634602 TI - Transforming growth factor-beta in disease: the dark side of tissue repair. PMID- 1634603 TI - Thyroid hormone modulation of the hypothalamic growth hormone (GH)-releasing factor-pituitary GH axis in the rat. AB - Both thyroid hormone and hypothalamic growth hormone (GH)-releasing factor (GRF) facilitate pituitary somatotroph function. However, the pathophysiological role of thyroid hormone in GRF secretion is less well understood. Thyrotoxicosis, induced by administration of thyroxine (T4) in rats, inhibited both pituitary GH levels and immunoreactive GRF secretion from incubated hypothalamus. At the highest dose of T4 given for 12 d, GRF secretion and pituitary GH decreased by 50 and 39%, respectively. Hypothyroidism induced by thyroidectomy (Tx) enhanced GRF secretion approximately twofold while depleting pituitary GH by greater than 99%. Both of these hypothalamic and pituitary effects were reversed by replacement of T4 but not human GH for 7 or 14 d. Human GH was as potent as T4 in restoring decreased body weight gains or serum insulin-like growth factor-1 levels in Tx rats. These results indicate that at both physiological and pathological concentrations in serum, thyroid hormone acts as an inhibitory modulator of GRF secretion, probably not involving a feedback mechanism through GH. A biphasic effect of thyroid hormone on pituitary GH levels appears to derive from the difference in primary target tissues of hyper- and hypothyroidism, the hypothalamus and the pituitary, respectively. PMID- 1634604 TI - Nuclear expression of the 50- and 65-kD Rel-related subunits of nuclear factor kappa B is differentially regulated in human monocytic cells. AB - The nuclear factor (NF)-kappa B transcription factor system is composed of at least four inducible nucleoprotein adducts termed p50, p55 (NF-kappa B p50), p75 (NF-kappa B p65), and p85 (c-Rel). These proteins are expressed in the nuclei of activated T cells in a distinctly biphasic fashion, with p55 and p75 induction occurring within minutes whereas the induction of p50 and p85 occurs after several hours. In contrast, p50 and p55 are constitutively expressed in the nuclei of U937 and THP-1 monocytic cells. However, cellular activation is required for the nuclear expression of p75 in these cells. Additionally, activation of monocytic cells does not result in a significant induction of p85. Tumor necrosis factor alpha induces the nuclear expression of p55 and p75 in these monocytic cells within 20 min, presumably reflecting the liberation of these proteins from I kappa B. In contrast, phorbol myristate acetate (PMA) induces the expression of these proteins with delayed kinetics, raising the possibility that PMA is incapable of mediating the efficient release of p55 and p75 from I kappa B in these cells. These findings highlight important differences in the regulation of these proteins in monocytic cells versus T cells and suggest that the induced expression of NF-kappa B p65 in monocytes may play a central role in the activation of HIV-1 gene expression. PMID- 1634605 TI - Human enterocyte (Caco-2) migration is modulated in vitro by extracellular matrix composition and epidermal growth factor. AB - The modulation of enterocyte sheet migration was studied using Caco-2 cells, a well-differentiated human colonic cell line. Although Caco-2 cells attached and spread equivalently over collagen types I, III, IV, and V and laminin, migration over laminin was significantly slower than migration over the collagen types. Fibronectin was a poor substrate for attachment, spreading, and migration. Epidermal growth factor (EGF) stimulated migration over laminin but did not alter Caco-2 migration over collagen or fibronectin. This effect was independent of cell proliferation, which was stimulated equivalently on both laminin and collagen I. Expression and organization of cell surface receptors for matrix (integrins) were studied using antibodies specific for beta and alpha integrin subunits. Integrin surface expression was assessed by immunoprecipitation of surface 125iodinated control and EGF-treated cells. Beta 1 surface pools did not change substantially in any condition studied. Alpha 1 subunit pools were decreased after EGF treatment on collagen I but alpha 1 pools increased after EGF treatment on laminin. Surface pools of alpha 2 subunits were increased following EGF treatment whether cells were cultured on laminin or collagen I. However, traditional immunofluorescent and laser confocal imaging demonstrated substantial differences in the character of alpha 2 subunit organization between collagen and laminin in the migrating cell front. Furthermore, a functional antibody to the alpha 2 subunit inhibited EGF stimulation of migration over laminin without substantial effects on basal migration over laminin or collagen I. Thus, EGF appears to exert a matrix-specific effect on enterocyte migration by modulation of integrin expression and organization. PMID- 1634606 TI - Identification of a genetic alteration in the code for bilirubin UDP glucuronosyltransferase in the UGT1 gene complex of a Crigler-Najjar type I patient. AB - Patients with Crigler-Najjar syndrome (CN) type I inherit an autosomal recessive trait for hyperbilirubinemia, which is characterized by the total absence of bilirubin UDP-glucuronosyltransferase (transferase) activity. The recent identification of two bilirubin transferase isoforms with identical carboxyl termini (Ritter, J. K., J. M. Crawford, and I. S. Owens. 1991. J. Biol. Chem. 266:1043-1047) led to the discovery of a unique locus, UGT1, which encodes a family of UDP-glucuronosyltransferase isozymes, including the two bilirubin forms (Ritter, J. K., F. Chen, Y. Y. Sheen, H. M. Tran, S. Kimura, M. T. Yeatman, and I. S. Owens. 1992. J. Biol. Chem. 267:3257-3261). The UGT1 locus features a complex of six overlapping transcriptional units encoding transferases, each of which shares the four most 3' exons (2, 3, 4, and 5) specifying the 3' half of the transferase coding regions (condons 289-533) and the entire 3' untranslated region of each mRNA. This gene model predicts that a single critical mutation in any of these four "common" exons may inactivate the entire family of encoded transferases. In agreement with this prediction, we show here that in the first CN type I individual analyzed (patient F.B.), a 13-bp deletion has occurred in exon 2. Analysis of product generated by the polymerase chain reaction and genomic DNA demonstrated that F.B. is homozygous for the defective allele (UGT1*FB), and that the consanguineous parents are both heterozygotic at this locus. The mutation is predicted to result in the synthesis of severely truncated bilirubin transferase isozymes that are lacking a highly conserved sequence in the carboxyl-terminus and the characteristic membrane (endoplasmic reticulum) anchoring segment of the protein molecule. PMID- 1634607 TI - Identification of a common mutation in Finnish patients with nonketotic hyperglycinemia. AB - Nonketotic hyperglycinemia (NKH) is an autosomal recessive metabolic disorder caused by the defects in the glycine cleavage system (GCS; EC 2.1.2.10), a multienzyme system that consists of four individual components. NKH is a rare disorder in many countries, but with a very high incidence in northern Finland. To understand the genetic background of this high incidence, we examined the GCS in a typical case of NKH at the molecular level. The activity of P protein, a component of the GCS, was not detected in the lymphoblasts of the patient, while P protein mRNA of a normal size and level was present in the cells. Structural analysis of P protein mRNA from the patient revealed a single nucleotide substitution from G to T in the protein coding region, which resulted in an amino acid alteration from Ser564 to Ile564. No P protein activity was detected when the mutant P protein with this amino acid substitution was expressed in COS 7 cells. The patient was homozygous for this mutation. Furthermore, this mutation was present in 70% (14 of 20) of P protein gene alleles in Finnish patients with NKH, whereas it was not found in 20 alleles of non-Finnish patients. The results suggest that this mutation is responsible for the high incidence of NKH in Finland. PMID- 1634608 TI - A T cell-dependent experimental liver injury in mice inducible by concanavalin A. AB - Male NMRI or BALB/c mice developed severe liver injury as assessed by transaminase release within 8 h when an intravenous dose greater than 1.5 mg/kg concanavalin A (Con A) was given. Histopathologically, only the liver was affected. Electron micrographs revealed leukocyte sticking to endothelial cells and bleb formation of hepatocytes. The hepatotoxicity of the lectin correlated neither with its agglutination activity nor with its sugar specificity. Administration of 0.5 mg/kg dexamethasone or 50 mg/kg cyclosporine A or 50 mg/kg FK 506 (Fujimycin) resulted in protection of the animals whereas indomethacin pretreatment failed to protect. Con A hepatitis was accompanied by the release of IL-2 into the serum of the animals. Mice with severe combined immunodeficiency syndrome lacking B as well as T lymphocytes were resistant against Con A. Athymic nude mice with immature T lymphocytes were also resistant. Pretreatment of mice with an antibody against T lymphocytes fully protected against Con A as did monoclonal anti-mouse CD4. Monoclonal anti-mouse CD8 failed to protect. Pretreatment of mice with silica particles, i.e., deletion of macrophages, prevented the induction of hepatitis. These findings provide evidence that Con A induced liver injury depends on the activation of T lymphocytes by macrophages in the presence of Con A. The model might allow the study of the pathophysiology of immunologically mediated hepatic disorders such as autoimmune chronic active hepatitis. PMID- 1634609 TI - The familial hypercholesterolemia (FH)-North Karelia mutation of the low density lipoprotein receptor gene deletes seven nucleotides of exon 6 and is a common cause of FH in Finland. AB - A mutation of the LDL receptor gene very common among Finnish patients with heterozygous familial hypercholesterolemia (FH) was identified. This mutation, designated as FH-North Karelia, deletes seven nucleotides from exon 6 of the LDL receptor gene, causes a translational frameshift, and is predicted to result in a truncated receptor protein. Only minute quantities of mRNA corresponding to the deleted gene were detected. Functional studies using cultured fibroblasts from the patients revealed that the FH-North Karelia gene is associated with a receptor-negative (or binding-defective) phenotype of FH. Carriers of the FH North Karelia gene showed a typical xanthomatous form of FH, with mean serum total and LDL cholesterol levels of 12 and 10 mmol/liter, respectively. This mutation was found in 69 (34%) out of 201 nonrelated Finnish FH patients and was especially abundant (prevalence 79%) in patients from the eastern Finland. These results, combined with our earlier data on another LDL receptor gene deletion (FH Helsinki), demonstrate that two "Finnish-type" mutant LDL receptor genes make up about two thirds of FH mutations in this country, reflecting a founder gene effect. This background provides good possibilities to examine whether genetic heterogeneity affects the clinical presentation or responsiveness to therapeutic interventions in FH. PMID- 1634610 TI - Molecular basis of fibrinogen Naples associated with defective thrombin binding and thrombophilia. Homozygous substitution of B beta 68 Ala----Thr. AB - In an abnormal fibrinogen (fibrinogen Naples) associated with congenital thrombophilia we have identified a single base substitution (G----A) in the B beta chain gene that results in an amino acid substitution of alanine by threonine at position 68 in the B beta chain of fibrinogen. The propositus and two siblings were found to be homozygous for the mutation, whereas the parents and another sibling were found to be heterozygous. Individuals homozygous for the defect had a severe history of both arterial and venous thrombosis; heterozygous individuals had no clinical symptoms. The three homozygotes had a prolonged thrombin clotting time in plasma, whereas the heterozygotes had a normal thrombin clotting time. Fibrinopeptide A and B (FpA and FpB) release from purified fibrinogen by human alpha-thrombin was delayed in both the homozygous propositus and a heterozygous family member. Release of FpA from the normal and abnormal amino-terminal disulfide knot (NDSK) corresponded to that found with the intact fibrinogens, indicating a decreased interaction of thrombin with the NDSK part of fibrinogen Naples. Binding studies showed that fibrin from homozygous abnormal fibrinogen bound less than 10% of active site inhibited alpha-thrombin as compared with normal fibrin, while fibrin formed from heterozygous abnormal fibrinogen bound approximately 50% of alpha-thrombin. These results suggest that the mutation of B beta Ala 68----Thr affects the binding of alpha-thrombin to fibrin, and that defective binding results in a decreased release of FpA and FpB in both homozygous and heterozygous abnormal fibrinogens. PMID- 1634611 TI - Abnormal sympathetic overactivity evoked by insulin in the skeletal muscle of patients with essential hypertension. AB - The reason why hyperinsulinemia is associated with essential hypertension is not known. To test the hypothesis of a pathophysiologic link mediated by the sympathetic nervous system, we measured the changes in forearm norepinephrine release, by using the forearm perfusion technique in conjunction with the infusion of tritiated NE, in patients with essential hypertension and in normal subjects receiving insulin intravenously (1 mU/kg per min) while maintaining euglycemia. Hyperinsulinemia (50-60 microU/ml in the deep forearm vein) evoked a significant increase in forearm NE release in both groups of subjects. However, the response of hypertensives was threefold greater compared to that of normotensives (2.28 +/- 45 ng.liter-1.min-1 in hypertensives and 0.80 +/- 0.27 ng.liter-1 in normals; P less than 0.01). Forearm glucose uptake rose to 5.1 +/- .7 mg.liter-1.min-1 in response to insulin in hypertensives and to 7.9 +/- 1.3 mg.liter-1.min-1 in normotensives (P less than 0.05). To clarify whether insulin action was due to a direct effect on muscle NE metabolism, in another set of experiments insulin was infused locally into the brachial artery to expose only the forearm tissues to the same insulin levels as in the systemic studies. During local hyperinsulinemia, forearm NE release remained virtually unchanged both in hypertensive and in normal subjects. Furthermore, forearm glucose disposal was activated to a similar extent in both groups (5.0 +/- 0.6 and 5.2 +/- 1.1 mg.liter-1.min-1 in hypertensives and in normals, respectively). These data demonstrate that: (a) insulin evokes an abnormal muscle sympathetic overactivity in essential hypertension which is mediated by mechanisms involving the central nervous system; and (b) insulin resistance associated with hypertension is demonstrable in the skeletal muscle tissue only with systemic insulin administration which produces muscle sympathetic overactivity. The data fit the hypothesis that the sympathetic system mediates the pathophysiologic link between hyperinsulinemia and essential hypertension. PMID- 1634612 TI - Transplantation of thymic autoimmune microenvironment to severe combined immunodeficiency mice. A new model of myasthenia gravis. AB - To study the role of the thymus in the cellular pathogenesis of myasthenia gravis (MG) we transplanted thymus tissue fragments from MG thymuses beneath the kidney capsule of severe combined immunodeficiency (SCID) mice. Immunocytochemical studies documented that the human thymus tissues are accepted as long-term grafts in the host SCID mice, with human lymphocytes, thymic stroma, and thymic myoid cells demonstrable in transplanted thymus for at least 15 weeks after transplantation. Human anti-acetylcholine receptor antibodies became detectable 1 to 2 weeks after transplantation, and in most chimeras the titers increased over at least 11 weeks to reach levels typically found in severe human MG. Human Ig deposits were detected at skeletal muscle end-plates, demonstrating that the human (auto)antibodies bound to murine acetylcholine receptor. In contrast, transfers of dissociated thymus cells only lead to a transient increase of anti acetylcholine receptor antibodies. Our data prove that myasthenia gravis thymus is able to induce and maintain autoantibody production in immunodeprived host animals, and that this tissue contains all cellular components required for autoantibody production. Transplantation of solid thymus tissue seems to transfer an autoimmune microenvironment, which will allow direct studies of the mechanism of autosensitization inside the thymus. PMID- 1634613 TI - Induction of heme oxygenase is a rapid, protective response in rhabdomyolysis in the rat. AB - Heme proteins such as myoglobin or hemoglobin, when released into the extracellular space, can instigate tissue toxicity. Myoglobin is directly implicated in the pathogenesis of renal failure in rhabdomyolysis. In the glycerol model of this syndrome, we demonstrate that the kidney responds to such inordinate amounts of heme proteins by inducing the heme-degradative enzyme, heme oxygenase, as well as increasing the synthesis of ferritin, the major cellular repository for iron. Prior recruitment of this response with a single preinfusion of hemoglobin prevents kidney failure and drastically reduces mortality (from 100% to 14%). Conversely, ablating this response with a competitive inhibitor of heme oxygenase exacerbates kidney dysfunction. We provide the first in vivo evidence that induction of heme oxygenase coupled to ferritin synthesis is a rapid, protective antioxidant response. Our findings suggest a therapeutic strategy for populations at a high risk for rhabdomyolysis. PMID- 1634614 TI - Expression of a missense mutation in the messenger RNA for beta-myosin heavy chain in myocardial tissue in hypertrophic cardiomyopathy. AB - We have determined that a missense mutation in exon 13 of the beta-myosin heavy chain (beta MHC) gene is expressed in the messenger RNA (mRNA) isolated from a right ventricular endomyocardial biopsy obtained from the proband of a family with hypertrophic cardiomyopathy. The mutation is the result of a substitution of an adenine for a guanine residue in one allele of the beta MHC gene and creates a second recognition site for the restriction endonuclease Ddel in exon 13. The mutation is inherited in a Mendelian fashion and co-segregates with hypertrophic cardiomyopathy in this family. Complementary DNAs synthesized from RNA isolated from the endomyocardial biopsy were cloned into a plasmid vector and sequenced to confirm the expression of both the normal and mutant allele in mRNA of myocardial tissue. This is the first report of the transcription of a mutant beta MHC gene allele into mRNA of the myocardium. PMID- 1634615 TI - Chronic blockade of nitric oxide synthesis in the rat produces systemic hypertension and glomerular damage. AB - Tonic basal release of nitric oxide (NO) by vascular endothelial cells controls blood pressure (BP) in the basal state. In these studies we investigated the effects of chronic inhibition of basal NO synthesis in the rat for a 2-mo period. Significant systemic hypertension developed in chronically NO-blocked rats compared to controls. Marked renal vasoconstriction was also observed with elevations in glomerular blood pressure (PGC) and reductions in the glomerular capillary ultrafiltration coefficient (Kf). Chronically NO-blocked rats also develop proteinuria and glomerular sclerotic injury compared to controls. These studies therefore describe a new model of systemic hypertension with glomerular capillary hypertension and renal disease due to chronic blockade of endogenous NO synthesis. These observations highlight the importance of the endogenous NO system in control of normal vascular tone and suggest that hypertensive states may result from relative NO deficiency. PMID- 1634616 TI - Human hepatic lipocytes synthesize tissue inhibitor of metalloproteinases-1. Implications for regulation of matrix degradation in liver. AB - Hepatic lipocytes play a central role in the pathogenesis of liver fibrosis, both via production of extracellular matrix proteins and through secretion of matrix metalloproteinases. In this study, we have characterized lipocyte expression and release of tissue inhibitor of metalloproteinases-1 (TIMP-1), an important inhibitor of metalloproteinase activity, whose role in liver has not previously been examined. TIMP-1 was immunolocalized to human lipocytes, and secretion of TIMP-1 was confirmed by ELISA of culture media; (mean +/- SD) 159 +/- 79 ng of TIMP-1/10(6) cells per 24 h. Evidence for functional inhibitory activity of released TIMP-1 was obtained by (a) reverse zymography that demonstrated a single inhibitor band, M(r) 28 kD, that co-migrated with a TIMP-1-positive control sample; and (b) unmasking of inhibited gelatinase activity in lipocyte medium by separating it from TIMP-1 using gelatin sepharose chromatography; gelatinase activity in chromatographed medium increased more than 20-fold, compared with unfractionated medium, and could be reinhibited by adding back fractions that contained inhibitor. By Northern analysis, freshly isolated human lipocytes exhibited low levels of mRNA expression for TIMP-1, but this increased markedly relative to beta-actin expression with lipocyte activation during cell culture. We conclude that human hepatic lipocytes synthesize TIMP-1, a potent metalloproteinase inhibitor, and that TIMP-1 expression increases with lipocyte activation. These data indicate that hepatic lipocytes can regulate matrix degradation in the liver, and suggest that expression of TIMP-1 by activated lipocytes may contribute to the progression of liver fibrosis. PMID- 1634617 TI - Adenine nucleotides stimulate migration in wounded cultures of kidney epithelial cells. AB - Adenine nucleotides speed structural and functional recovery when administered after experimental renal injury in the rat and stimulate proliferation of kidney epithelial cells. As cell migration is a component of renal regeneration after acute tubular necrosis, we have used an in vitro model of wound healing to study this process. High density, quiescent monkey kidney epithelial cultures were wounded by mechanically scraping away defined regions of the monolayer to simulate the effect of cell loss after tubular necrosis and the number of cells that migrated into the denuded area was counted. Migration was independent of cell proliferation. Provision of adenosine, adenine nucleotides, or cyclic AMP increased the number of migrating cells and accelerated repair of the wound. Other purine and pyrimidine nucleotides were not effective. Arginine-glycine aspartic acid-serine peptide, which blocks the binding of extracellular fibronectin to its cell surface receptor, completely inhibited migration in the presence or absence of ADP. Very low concentrations of epidermal growth factor (K0.5 approximately 0.3 ng/ml) stimulated migration, whereas transforming growth factor-beta 2 was inhibitory (Ki approximately 0.2 ng/ml). Thus, adenosine and/or adenine nucleotides released from injured or dying renal cells, or administered exogenously, may stimulate surviving cells in the wounded nephron to migrate along the basement membrane, thereby rapidly restoring tubular structure and function. PMID- 1634618 TI - Molecular sieving of albumin by the ascending vasa recta wall. AB - Molecular sieving of albumin by ascending vasa recta. Evidence exists to support the presence of an extravascular pool of albumin in the renal medullary interstitium. This study used microperfusion in vivo to measure the transport of 125I-labeled albumin from descending (DVR) and ascending vasa recta (AVR) to the papillary interstitium. Perfusions were performed during furosemide diuresis with a buffer containing FITC-labeled dextran (FITC-Dx) 2 x 10(6) mol wt and 125I albumin. Perfusate albumin and collection pressure were adjusted to induce either zero transcapillary volume flux (Jv) or high volume flux. When Jv was zero, the collectate-to-perfusate ratios of FITC-Dx (RDX) and 125I-albumin (Ralb) in the DVR and AVR were identical implying that diffusive efflux of albumin was immeasurably small. In contrast, when Jv was increased, paired comparison of Ralb and RDX in the same AVR revealed a difference, 1.58 +/- 0.06 vs 1.72 +/- 0.08, respectively (P less than 0.01). AVR perfusions in hydropenic animals showed similar results, Ralb = 1.70 +/- 0.07 and RDX = 2.00 +/- 0.07 (P less than 0.01). These data suggest that albumin transport across vasa recta in vivo is likely to be governed by solvent drag. The reflection coefficient of the AVR wall to 125I albumin is estimated to be 0.78. PMID- 1634620 TI - Multiple deletions of mitochondrial DNA in several tissues of a patient with severe retarded depression and familial progressive external ophthalmoplegia. AB - Multiple deletions of mitochondrial DNA (mtDNA) have recently been reported in familial progressive external ophthalmoplegia (PEO), in a case of progressive encephalomyopathy, and in inherited recurrent myoglobinuria. The inheritance of familial PEO has been autosomal dominant, which indicates that a mutation in an unknown nuclear gene results in several mtDNA deletions of different sizes in these patients. We report a patient with autosomal dominant PEO, whose major clinical symptom, however, was severe retarded depression. The morphological analyses of the tissue samples derived from autopsy showed various abnormalities in the mitochondria in all the tissues studied. The activities of the respiratory chain enzymes encoded by mtDNA were remarkably reduced in the skeletal muscle. The mtDNA analyses confirmed that besides myopathy, this patient had a multisystem disorder with widespread distribution of multiple deletions of mtDNA. The highest percentage of mutated mtDNA was found in the brain, skeletal muscle and the heart, the relative quantity of mutated mtDNA correlating to the severity of the clinical symptoms. PMID- 1634619 TI - Dog mastocytoma cells produce transforming growth factor beta 1. AB - Transforming growth factor-beta (TGF beta) promotes deposition of extracellular matrix and is associated with fibrotic conditions both in experimental animals and in humans. Although a role for mast cells has been suspected in the pathogenesis of fibrosis, no potent mediator capable of stimulating fibroblast growth or extracellular matrix deposition has been identified in mast cell supernatants. We report here the constitutive production of TGF beta 1 by four dog mastocytoma cell lines. TGF beta 1 was identified by characteristic biologic activity, blockade of biologic effect by specific neutralizing antibody, and by recognition of a band with the appropriate migration by western blot. TGF beta 1 mRNA, but not TGF beta 2 or TGF beta 3 mRNA, was also produced constitutively by all four cell lines. Quantitation by bioassay revealed baseline TGF beta secretion of approximately 1 ng/10(6) cells over 48 h. Stimulation of mastocytoma cells with phorbol ester increased the rate of release of TGF beta 1, most markedly in the first 30 min after stimulation, without increasing TGF beta 1 mRNA. Dog mastocytoma cells produced TGF beta 1 primarily in a latent form, inactive until treated with acid. Both pure TGF beta 1 and TGF beta-containing mastocytoma cell-conditioned media inhibited mitogenesis and proliferation in dog mastocytoma cell lines, suggesting that mast cell tumor lines would not grow preferentially based on their ability to produce TGF beta. These studies may make possible further investigation of the mechanism by which mast cells contribute to the induction of fibrosis. PMID- 1634621 TI - Fibrinogen Lima: a homozygous dysfibrinogen with an A alpha-arginine-141 to serine substitution associated with extra N-glycosylation at A alpha-asparagine 139. Impaired fibrin gel formation but normal fibrin-facilitated plasminogen activation catalyzed by tissue-type plasminogen activator. AB - An A alpha-arginine-141 to serine substitution has been identified in a homozygous dysfibrinogen, fibrinogen Lima, associated with impaired fibrin polymerization. The point mutation created an asparagine-X-serine-type glycosylation sequence, and indeed, extra, mainly disialylated biantennary oligosaccharides have been isolated from A alpha asparagine-139 of the patient's fibrinogen. This type of glycosylation sequence is unique for human fibrinogen, because the sequences shown for normal and abnormal fibrinogens are all asparagine-X-threonine types. The terminal sialic acids of the extra oligosaccharides seem to have largely contributed to the impaired fibrin gel formation, as evidenced by its correction to a near normal level by desialylation. Nevertheless, the polymerizing fibrin facilitated tissue-type plasminogen activator-catalyzed plasmin formation in a normal fashion, indicating that the initial two-stranded fibrin protofibrils had been constructed normally. Thus the impaired fibrin gel formation could be attributed to the delay in their subsequent lateral association, most probably because of the repulsive forces generated by the negative electric charge of the extra sialic acids. The substitution of a basic residue arginine to a noncharged residue serine may also have contributed to the impaired function in a similar manner or by steric hindrance in association with bulky extra oligosaccharide chains. PMID- 1634622 TI - The loss of GLUT2 expression by glucose-unresponsive beta cells of db/db mice is reversible and is induced by the diabetic environment. AB - Glucose-induced insulin secretion by beta cells of diabetic db/db mice was studied by a pancreas perfusion technique, and the levels of GLUT2 protein in pancreatic islets were assessed by immunofluorescence microscopy and protein blot analysis. Beta cells from diabetic mice had a high basal rate of insulin secretion; they did not respond to glucose stimulation but displayed a normal secretory response to arginine. At the same time, GLUT2 expression by db/db islets was lost whereas beta cells from nondiabetic db/+ mice expressed high levels of this transporter. GLUT2 levels in liver or kidney of diabetic mice were, however, mostly unaltered. Transplanting islets from db/db mice under the kidney capsule of db/+ mice restored normal GLUT2 levels. Conversely, transplantation of db/+ islets into db/db mice induced the disappearance of GLUT2 expression. When islets from db/+ mice were transplanted under the kidney capsule of streptozocin-diabetic mice, the immunodetection of GLUT2 also disappeared. We conclude that: (a) GLUT2 expression is decreased in glucose-unresponsive beta cells from db/db mice; (b) the decreased expression of GLUT2 is reversible; (c) the loss of GLUT2 expression is induced by the diabetic environment of db/db and streptozocin-induced diabetic mice. These observations together with previously published data suggest that a factor different from glucose or insulin regulates the beta cell expression of GLUT2. PMID- 1634624 TI - Radiographic evaluation of early periodontal bone loss in adolescents. An overview. AB - A number of studies have used radiographs to establish the prevalence of periodontal bone loss in adolescents, though widely differing findings have been reported. It is likely that such disparity of results can largely be attributed to the variety of criteria used to determine the presence of disease, some of which are highly subjective. In addition, a number of factors may affect the radiographic appearance of commonly chosen reference points. If epidemiological studies are to be interpreted correctly, it is important to examine these areas and, in particular, to determine the most objective means of recording disease in this age group. From a review of the literature, it would seem that assessments based on the radiographic distance between the amelo-cemental junction and the alveolar crest are the least subjective, yet whether this should be greater than 2 mm or 3 mm before bone loss is recorded, is still debated. PMID- 1634623 TI - Interactions of surfactant protein D with bacterial lipopolysaccharides. Surfactant protein D is an Escherichia coli-binding protein in bronchoalveolar lavage. AB - Surfactant protein D (SP-D) is a collagenous glycoprotein that is secreted into the pulmonary airspaces by alveolar type II and nonciliated bronchiolar cells. SP D exhibits Ca(++)-dependent carbohydrate binding in vitro and is structurally related to the collagenous C-type lectins, including serum conglutinin, serum mannose-binding proteins, and surfactant protein A. Preliminary studies showed calcium- and saccharide-dependent binding of fluorescein-conjugated or radioiodinated SP-D to a variety of microorganisms, including Gram-negative bacteria and fungi. A laboratory strain of Escherichia coli (Y1088) was chosen to further examine the mechanism(s) of binding. Binding of SP-D to Y1088 was time dependent, saturable, and inhibited by cold SP-D or competing saccharides; Scatchard analysis gave a Kd of 2 x 10(-11) M. At higher concentrations, SP-D also caused Ca(++)-dependent agglutination of Y1088 that was inhibited by alpha glucosyl-containing saccharides, antisera to the carbohydrate-binding domain of SP-D, or Y1088 LPS. Lectin blots showed specific binding of 125I-SP-D to Y1088 LPS, as well as LPS from other several strains of enteric Gram-negative bacteria. Immunogold studies demonstrated strong and uniform surface labeling of the bacteria. Rat and human bronchoalveolar lavage (BAL) caused Ca(++)-dependent agglutination of E. coli that was dose dependent and inhibited by competing saccharides or anti-SP-D. SP-D was selectively and efficiently adsorbed from rat BAL by incubation with E. coli, and incubation of E. coli with radiolabeled rat type II cell medium revealed that SP-D is the major E. coli-binding protein secreted by freshly isolated cells in culture. We suggest that SP-D plays important roles in the lung's defense against Gram-negative bacteria. PMID- 1634625 TI - Prevalence of juvenile periodontitis in a circumpubertal population. AB - A cross-sectional radiographic screening was performed on bite-wing pairs (BW) from 1872 10-12 year old schoolchildren in the Greater Worcester, Massachusetts area to assess the prevalence of juvenile periodontitis (JP). The 3-stage screening process entailed: (1) visual identification of possible cases based upon a visual assessment of BW for interproximal crestal bone levels greater than or equal to 2 mm from the cemento-enamel junction (CEJ) on greater than or equal to 1 permanent first molar; (2) identification of probable cases based upon BW from possible cases measured with a transparent ruler calibrated in millimeters; (3) finally, clinical confirmation of JP in consenting probable cases. A total of 1038 subjects were eligible to be included in the study (greater than or equal to 3 mesial sites readable). Of the 1038 eligible subjects, 117 possible and 103 probable cases were identified in stage 1 and stage 2, respectively. A total of 99 probable cases could be contacted and 43 were examined clinically. Two cases of JP were confirmed clinically in stage 3, yielding a prevalence rate of 4.6/1000. Specifically, this report defines a rate of JP in 10-12 year-old schoolchildren for the first time. In addition, these results indicate that BW can be used to identify children with JP from large data sets. However, further studies including complete clinical and radiographic examinations are necessary to determine whether this method is adequate for large epidemiologic studies. PMID- 1634626 TI - Guided tissue regeneration combined with osseous grafting in suprabony periodontal lesions. An experimental study in the dog. AB - The purpose of the present investigation was to evaluate the use of bone grafts in combination with the GTR-procedure in reinstituting periodontal support around teeth with horizontal bone loss. Orthodontic elastic bands were placed around mandibular and maxillary premolars in 3 dogs in order to induce breakdown of the periodontal tissues. When the destruction had reached a level corresponding to approximately half the root length, the elastic bands were removed and the teeth were scaled. After a period with plaque control, mucoperiosteal flaps were elevated on the buccal and lingual aspects of the experimental teeth. The exposed root surfaces were curetted, and a notch was made at the level of the reduced bone crest. In randomly selected test quadrants, Kielbone mixed with fibrin sealant (Tisseel) was placed in the interproximal space and in the bifurcations. Both the buccal and lingual aspect of the test teeth were then covered by a teflon membrane (Zitex) and the raised tissue flaps sutured in a coronally displaced position. The contralateral teeth (controls) were treated the same way, except that fibrin sealant without Kielbone was applied in the bifurcations and the interproximal space prior to the placement of the membranes. The membranes were removed by a 2nd operation after 35 days. Clinically, various complications were observed during healing. The buccal and lingual flap margins consistently failed to join in the interproximal area, and increasing recession of the flap margins and exposure of the membranes, resulting in accumulation of bacterial deposits and food debris, occurred during the period the membranes were maintained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634628 TI - High-speed filming of the Periotest measurement. AB - Periodontal disease may be diagnosed with the Periotest technique, which involves electronically controlled and reproducible percussion of tooth. The movement on percussion was investigated with high-speed film and then compared with the return of teeth after static deflection for several seconds as has been reported previously by Lukas and Scholz. The elastic and viscous properties of the periodontium and the surrounding bony tooth socket are to a large extent non linear. The 10-20 microns deflection of the healthy tooth represents only a fraction of static tooth mobility published by Parfitt or Schulte et al. The visco-elastic properties of a healthy tooth enabling the percussion of the Periotest tapping head to be decelerated in less than 1 ms are largely lost in periodontitis. It is this essential difference which the Periotest method utilizes. PMID- 1634627 TI - A randomized trial of occlusal adjustment in the treatment of periodontitis patients. AB - The purpose of the randomized clinical trial was to test; (1) the influence of occlusal adjustment (OA) in association with periodontal therapy on attachment levels, pocket depth, and tooth mobility, (2) whether OA was of greater significance in non-surgically treated periodontal defects, and (3) whether initial tooth mobility or disease severity had an affect on post-treatment attachment levels following OA. After hygienic-phase therapy, 50 patients received OA/No OA according to random assignment; 22 patients received an OA and 28 were not adjusted. 2 months after OA, either modified Widman flap surgery or scaling and root planing by a periodontist were done according to random assignment within each patient in a split-mouth design. Following active treatment patients were maintained with prophylaxis done every 3 months and scored annually. For the analysis of this two-year data, a repeated measures analysis of variance was performed using attachment level change and pocket depths as outcome indicators. There was significantly greater gain of clinical periodontal attachment in patients who received an OA compared to those who did not. Both the surgically and non-surgically treated sides of the mouth responded similarly to OA. There was no affect of OA on the response in pocket depth, nor did initial tooth mobility or initial periodontal disease severity influence the response to OA. PMID- 1634629 TI - Use of toothpicks for chlorhexidine staining. AB - The purpose of this study was to determine if the extrinsic dental staining associated with the use of chlorhexidine gluconate (CHX) mouthrinse could be prevented or controlled by the patient with the use of toothpicks. 25 subjects received a prophylaxis to establish a stain-free baseline and were then randomly assigned a control and experimental side of the mouth. The rinsing regimen was 1/2 oz of 0.12% CHX mouthrinse 2x a day for 3 months. Subjects self-examined daily for the appearance of stain. Where stain was visible, a toothpick was used to 'rub it away' on the distolabial, labial and mesiolabial surfaces of the experimental side only. The rubbing action was similar to the use of an eraser to remove a pencil mark from paper. The amount and intensity of stain was photographed and graded by a blinded examiner after 2 weeks, 1, 2 and 3 months. Subjects kept calendars to encourage and document compliance. When analyzed across time, teeth and surfaces, there was a statistically significant difference in stain between the control and experimental sides for stain amount, intensity, and for a composite of amount/intensity. Clinical differences were slight. The study indicates that the use of a simple toothpicking technique can affect chlorhexidine stain. PMID- 1634630 TI - Subgingival temperature (I). Relation to baseline clinical parameters. AB - 44 subjects ranging in age from 14-71 years were measured at 6 sites per tooth for gingival redness, plaque accumulation, suppuration, bleeding on probing, pocket depth and attachment level. Subgingival temperatures were measured at the same 6 sites per tooth using a periodontal temperature probe (Periotemp, Abiodent, Danvers, MA). This instrument was also used to measure each subject's sublingual temperature in order to compute the differences between sublingual and subgingival temperature. Relationships were sought between the baseline clinical parameters and the temperature variables in subjects and at sites. The mean and standard deviation of the sublingual temperatures for the 44 subjects was 36.6 +/ 0.4 degrees C (range 35.8-37.6 degrees C). The mean of each subject's mean whole mouth subgingival temperature was 1.9 degrees C lower, 34.8 +/- 0.6 degrees C (range 33.4-36.1 degrees C). The differences of the mean subgingival temperature from sublingual ranged from -0.8 to -3.2 degrees C (average -1.9 +/- 0.5 degrees C). Mean temperature difference for a subject correlated with % of sites with plaque (rs = 0.45), redness (rs = 0.33), bleeding on probing (rs = 0.44), % of sites with attachment level greater than 3 mm (rs = 0.44), mean pocket depth (rs = 0.44) and mean attachment level (rs = 0.39). There were higher mean temperatures at sites exhibiting or not exhibiting plaque (35.0, 34.5 degrees C), redness (34.9, 34.6), bleeding on probing (35.1, 34.7) and suppuration (35.4, 34.8). Sites with pockets less than 4, 4-6 and greater than 6 mm had mean temperatures of 34.6, 35.2, 35.8 degrees C, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634631 TI - Subgingival temperature (II). Relation to future periodontal attachment loss. AB - The purpose of the present investigation was to determine whether subgingival temperature was a risk indicator of periodontal attachment loss (detected in the following 2 months) in a subject or at a site. 29 subjects were measured at 6 sites per tooth for clinical parameters as well as subgingival temperature using a periodontal temperature probe (Periotemp, ABIO-DENT, Danvers, MA). The same instrument was used to measure sublingual temperature in order to compute differences between subgingival and sublingual temperature. Clinical and temperature parameters were measured at 2-month intervals. A total of 49 subject visits which had both baseline temperature and subsequent attachment level change measurements were available for analysis. Attachment level loss greater than 2.5 mm occurred at 1 or more sites at 16 of 49 subject visits. Elevated mean subgingival temperature was related to subsequent attachment loss particularly in individuals who exhibited more than 1 progressing site. The odds ratios of a subject exhibiting new attachment loss at 1 or more sites or at 2 or more sites were 14.5 and 64.0 if the subject's mean subgingival temperature exceeded 35.5 degrees C. Subjects with high mean subgingival temperatures and widespread periodontal destruction appeared to be at greatest risk for new attachment loss. Discriminant analysis using % of sites with suppuration, redness and attachment level greater than 3 mm and mean site temperature correctly "predicted" disease activity with a sensitivity, specificity and overall agreement of 0.75, 0.76 and 0.82 respectively. Of 7243 sites, 43 (0.59%) and 160 (2.2%) showed attachment loss of either 2.5 mm or more or 2 mm or more respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634632 TI - Clinical evaluation of a light energy conversion toothbrush. AB - A blind, two-way crossover clinical trial was carried out to compare the effectiveness of plaque removal between a new, light energy conversion toothbrush incorporated with a semiconductor of TiO2 (test) and a similar toothbrush without the semiconductor (control). The study was completed by 73 school children aged 13-15 years. Each toothbrush was used for a period of 3 weeks. The mean differences between baseline plaque scores and after subjects used the test and control brushes were analyzed by the paired t-test. The Soladey 2 toothbrush showed significantly more reduction of plaque on the buccal surfaces of all teeth than the control brush. There was no significant difference in the plaque removing ability of the two brushes on the lingual aspects of the mandible and on the lingual surfaces of the maxillary posterior sextant. As the buccal surfaces are more likely to allow light to reach the semiconductor during brushing than the lingual areas, it is possible that the reported photocatalytic property of the semiconductor may be involved in some way in the observed reduction of plaque. PMID- 1634633 TI - Periodontal status of older Floridians. PMID- 1634635 TI - Thoughts on drug development. PMID- 1634634 TI - Prepubertal periodontitis. PMID- 1634636 TI - The case conference approach to teaching clinical pharmacology. AB - This article analyzes the development of the small group case conference format, historically, elsewhere, and at the authors' institution, as a way of introducing second-year medical students enrolled in a basic pharmacology course to the practicalities, nuances, and challenges of contemporary drug therapy. A number of goals and purposes for these conferences have been identified and incorporated into the development and execution of a plan carried out over the past 14 years. Two examples of the conferences were presented, including an analysis of their teaching features. A listing of the general topics of 40 individual conferences used by the authors was provided. The authors reviewed evidence based on several methods of evaluation that the conferences are enthusiastically accepted by second-year medical students as an adjunctive approach to teaching both basic and applied clinical pharmacology. In addition, the authors find that the conferences subserve a number of other teaching functions such as problem-solving, information retrieval and presentation, and peer co-instruction. The conferences provide a mechanism for faculty-student interaction and an additional way to evaluate student knowledge and performance beyond the more conventional examination approaches. PMID- 1634637 TI - A nineteen-year-old man with altered mental status. PMID- 1634638 TI - The role of ambulatory monitoring of the blood pressure for assessment of antihypertensive agents. AB - For many decades, the casual blood pressure (BP) has been the standard for assessing BP response to antihypertensive agents in clinical trials. Noninvasive ambulatory BP technology has improved vastly in the last 15 years and has been increasingly used in dose-response studies as well as efficacy trials. Through these studies we have learned that casual BP may not be representative of the average daily blood pressure, that it may be quite susceptible to observer bias, and that it may result in inaccurate calculation of the trough-to-peak ratio of an antihypertensive drug. Perhaps more importantly is that a large body of data now supports the superiority of average daily BP over that of the casual or clinic BP in predicting several indexes of hypertensive target organ damage. Thus, use of the ambulatory BP technique in antihypertensive trials yields BP data that are far less susceptible to improper diagnosis and are representative of the hypertensive burden that causes vascular disease. PMID- 1634639 TI - Insulin resistance, hyperinsulinemia, dyslipidemia, hypertension, and accelerated atherosclerosis. AB - Hypertension is only one component of a multifaceted metabolic-hemodynamic complex that also includes obesity, subtle and overt glucose intolerance, dyslipidemia, enhanced vascular resistance and accelerated atherosclerosis. Results of a number of studies in the past 5 years have shown that even nonobese, nondiabetic individuals with hypertension display insulin resistance, which is located in peripheral tissues (primarily skeletal muscle), is limited to nonoxidative pathways of glucose disposal, and appears to be directly correlated with the severity of hypertension. Insulin resistance and associated hyperinsulinemia in hypertensive individuals are also associated with increased plasma triglyceride levels and decreased high-density lipoprotein concentrations, which likely contributes to enhanced atherosclerosis. Hyperinsulinemia may directly promote atherosclerosis by enhancing LDL-cholesterol accumulation in vessel walls, vascular smooth muscle migration, and proliferation, augmenting connective tissue synthesis in the vascular wall, and decreasing the regression of lipid plaques. The enhanced peripheral vascular resistance that characterizes insulin resistance/hyperinsulinemic states may be related to decreased vascular smooth muscle responses to insulin, which normally modulates (attenuates) vascular contractile responses to vasoactive agents. PMID- 1634640 TI - Cholestyramine-induced hyperchloremic metabolic acidosis. AB - Cholestyramine is a nonabsorbable anion exchange resin that is used predominantly for the treatment of hypercholesterolemia in adults and the management of acute diarrhea in children. The authors report two cases of severe hyperchloremic nonanion gap metabolic acidosis associated with the use of cholestyramine therapy. The authors recommend that patients taking cholestyramine who have concomitant renal insufficiency or who are volume depleted or who are taking spironolactone be monitored carefully for the emergence of a hyperchloremic metabolic acidosis. PMID- 1634641 TI - Lovastatin alters blood rheology in primary hyperlipoproteinemia: dependence on lipoprotein(a)? AB - As part of a randomized, single-blind, comparative study evaluating the efficacy of lovastatin and bezafibrate retard in the treatment of primary hypercholesterolemia, hemorheologic parameters (whole blood viscosity, hematocrit, plasma viscosity, red blood cell aggregation and deformability, and fibrinogen) were studied in 35 patients. Whole blood viscosity and plasma viscosity improved significantly after 3 months of treatment with lovastatin, whereas other hemorheologic variables remained unchanged. Stratifying 24 patients by their lipoprotein Lp(a) levels showed that in those with low Lp(a) (less than or equal to 25 mg/dL) high-density lipoprotein cholesterol increased and red blood cell aggregation as well as deformability decreased considerably, whereas in the group with high Lp(a) levels (greater than 25 mg/dL), the opposite behavior was observed. Treatment of primary hypercholesterolemia with lovastatin may not only reduce the risk for atherosclerotic complications by its pronounced decrease of low-density lipoprotein cholesterol, but also may favorably alter blood rheology, and may decrease insudation of plasmatic components into the arterial wall and improve tissue perfusion, in particular on the microcirculatory level. The possible relevance of Lp(a) levels for the hemorheologic effects of lovastatin remains to be elucidated. PMID- 1634642 TI - A comparison of tablets with oral suspension formulation of dipyridamole in thallium myocardial imaging. AB - Dipyridamole stress thallium imaging has been widely employed to diagnose and assess the extent of coronary heart disease in patients who cannot exercise. When oral dipyridamole administration was used, a wide range of results for sensitivity, specificity, hemodynamic response and side effect profile has been reported. The authors hypothesized that the formulation used for oral administration of dipyridamole plays a major factor in this variability, and that the pulverized form of dipyridamole will achieve faster and more consistent response than the standard tablet form. The authors studied 13 consecutive patients who underwent thallium scintigraphy. Eight patients received dipyridamole pulverized and dissolved in a glycol/aqueous base diluent (group A), and five patients received the standard form of dipyridamole (group B). In group A, mean peak systolic blood pressure decreased from 142 +/- 31 (mean +/- standard deviation) to 109 +/- 30 (P = .05), and mean diastolic blood pressure decreased from 76 +/- 14 to 51 +/- 5. The mean heart rate changed from 78 +/- 26 to 80 +/- 10. In group B, baseline systolic blood pressure was 165 +/- 12 and decreased to 156 +/- 7 at 45 minutes and to 155 +/- 14 at 90 minutes. Heart rate increased from baseline of 69 +/- 9 to 75 +/- 8 at 45 minutes and to 76 +/- 11 at 90 minutes. At 45 minutes, the systolic blood pressure of the 8 group A patients dropped by 33 +/- 19 mm Hg, whereas group B's changed by 9 +/- 6 mm Hg (P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634643 TI - Evaluation of bioavailability and pharmacokinetics of two isosorbide-5 mononitrate preparations in healthy volunteers. AB - The objective of this study was to determine both the pharmacokinetic parameters and the bioavailability of two commercial 20-mg isosorbide-5-mononitrate (IS-5 MN) preparations (test and reference preparation) after single oral administration. For this purpose, the test and the reference preparation were examined in 24 healthy male volunteers according to a randomized 2-way cross-over design, blood samples were withdrawn up to 24 hours postadministration, and plasma concentrations of IS-5-MN were quantified by a gas chromatography (GC) method. Both preparations led to peak plasma levels of approximately 360 ng/mL IS 5-MN in the mean 0.76 hour (test) and 0.94 hour (reference preparation) after application; the plasma half-lives were about 5.2 hours, and for the areas under the curve (AUC(0-infinity)), mean values of 2741 (test preparation) and 2742 hour.ng/mL (reference preparation) were found. The statistical comparison (analysis of variance, confidence intervals) of the pharmacokinetic parameters found in the study resulted in bioequivalence of both IS-5-MN preparations. The undesired side effects/concomitant symptoms observed are known to occur after IS 5-MN administration. PMID- 1634644 TI - Effect of moricizine on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers. AB - Moricizine HCl, a new orally active antiarrhythmic agent, induces its own hepatic metabolism and consequently may interfere with the metabolism of warfarin, a drug used commonly by cardiac patients that also is subject to extensive hepatic metabolism. Both drugs are also highly protein bound in plasma. To assess the possibility of an interaction, single-dose sodium warfarin (25 mg oral Coumadin, Du Pont Pharmaceuticals, Wilmington, DE) pharmacokinetics, pharmacodynamics; and plasma protein binding were examined in 12 healthy male volunteers 14 days before and 14 days after starting chronic oral moricizine HCl administration (250 mg every 8 hours). The terminal elimination rate constant of warfarin was increased by about 10% when measured in the presence of chronic moricizine administration. However, oral plasma clearance, apparent volume of distribution, maximum peak plasma concentration, time to reach peak concentration, and protein binding were unaffected. More importantly, there was no evidence of a pharmacodynamic interaction based on the prothrombin time profile. It was concluded that no clinically significant interaction occurs under these conditions. PMID- 1634645 TI - Effectiveness of antihypertensive medications in office and ambulatory settings: a placebo-controlled comparison of atenolol, metoprolol, chlorthalidone, verapamil, and an atenolol-chlorthalidone combination. AB - In a double-blind, crossover study, five white men with mild-to-moderate hypertension received placebo and fixed doses of atenolol, metoprolol, chlorthalidone, verapamil, and the combination of atenolol and chlorthalidone in a quasi-random order. Daily dosages were: atenolol, 100 mg; metoprolol, 200 mg; chlorthalidone, 50 mg; verapamil, 240 mg; and the same doses of atenolol and chlorthalidone in combination. Standard office and daytime ambulatory blood pressures were assessed at the end of each month-long trial. Atenolol, metoprolol, chlorthalidone, and verapamil controlled office blood pressure with similar reductions. Verapamil did not lower ambulatory blood pressure at this dose (which is lower than is now commonly used), but reductions in ambulatory blood pressure were similar for atenolol, metoprolol, and chlorthalidone. The combination of atenolol and chlorthalidone maintained blood pressure control more effectively than the single drug treatments in both office and ambulatory settings, and the combined hypotensive effects were additive. However, reductions in the office due to the combination appeared to overestimate hypotensive effectiveness in the ambulatory setting. This study suggests that the effectiveness of commonly prescribed antihypertensive regimens varies according to setting as well as drug, and that assessment of treatment effectiveness can be improved by automated ambulatory blood pressure monitoring. PMID- 1634646 TI - Multiple dose pharmacokinetics of four different doses of nisoldipine in hypertensive patients. AB - This randomized double-blind parallel group study characterized the pharmacokinetics of the calcium channel antagonist, nisoldipine (core-coat tablets), administered once daily for 7 days in doses of 5 mg (n = 12), 10 mg (n = 13), 20 mg (n = 12), and 30 mg (n = 11) to patients with mild to moderate hypertension. Serial blood samples were obtained from 0 to 24 hours and from 0 to 48 hours after nisoldipine administration on days 1 and 7, respectively. Nisoldipine plasma concentrations were determined by gas chromatography with electron capture detection. No statistically significant difference was found in dose-normalized area under the curve between the four groups. Area under the curve (standardized to body weight) correlated to dose (r = .74, P less than .05). No significant difference existed in oral clearance (L/h/kg) when analyzed for equivalence across the four doses: 8.21 +/- 3.47 (5 mg), 11.84 +/- 13.85 (10 mg), 11.48 +/- 7.49 (20 mg), and 10.36 +/- 5.49 (30 mg). The present investigation characterizes the pharmacokinetics of nisoldipine core-coat tablets in hypertensive patients and demonstrates the dose proportionality or linearity of nisoldipine plasma concentrations and area under the curve, measured over a dose range of 5 to 30 mg. PMID- 1634647 TI - Comparison of plasma nicotine concentrations after application of nicoderm (nicotine transdermal system) to different skin sites. AB - Drug absorption through the skin can vary according to the application site. The nicotine transdermal system, Nicoderm (Alza Corp., Palo Alto, CA) contains a rate controlling membrane designed to regulate delivery of nicotine to the skin and thus limit variability in nicotine plasma levels. Plasma nicotine concentrations were compared after application of NTS 14 mg/day to three different skin sites (upper back, upper outer arm, upper chest) in a randomized, crossover study involving 12 healthy male smokers. Plasma nicotine profiles from all three sites were similar: nicotine concentrations increased rapidly within 2 to 4 hours, reached broad peaks of approximately 11 to 14 ng/mL, and then remained relatively constant between 8 and 24 hours after application. The mean nicotine maximum peak plasma concentration values for nicotine transdermal system application to the arm, back, and chest were equivalent (13.8, 14.6, and 13.2 ng/mL, respectively). The mean time to reach peak concentration (tmax) (3 to 6 hours), and area under the curve (168, 186, and 183 ng.h/mL) values for the arm, back, and chest, respectively, were not significantly different. Thus, bioequivalent plasma nicotine concentrations were achieved irrespective of the application site on the upper body. PMID- 1634648 TI - References to contemporary papers on acoustics. PMID- 1634649 TI - The nurse and the firing squad. PMID- 1634650 TI - Milestones in Canadian nursing history. PMID- 1634651 TI - Changing times--changing nations. PMID- 1634652 TI - The future of nursing research in ethics and law. PMID- 1634653 TI - Funding of schools of nursing. PMID- 1634654 TI - The first 5 years after the dissertation. AB - To succeed in academia, nursing faculty members must devote the first 5 years following the dissertation to achieving a standard to tenure characteristic of the profession. Most institutions in the country adhere to the American Association of University Professors' guidelines for tenure. These guidelines mandate excellence in teaching, scholarship, and service. A fourth characteristic, leadership, is increasingly considered in tenure decisions. The expectations of an academic career in nursing serve as the foundation for a framework to evaluate the likelihood of success in a particular setting. A detailed 5-year plan for achieving tenure is proposed. PMID- 1634655 TI - Faculty performance appraisal systems: procedures and criteria. AB - This study investigated the consensus among schools of nursing in (1) using the eight elements of effective performance appraisal identified in the literature and (2) identification of domains, dimensions, and subdimensions of faculty performance. Content analysis was done of actual policies, procedures, and forms from 86 schools with graduate programs. Performance appraisal systems were found to be in an early stage of development. There was substantive agreement on teaching, service, and research as domains, with 25% or fewer schools also using faculty development, professional practice, and/or administration. There was less consensus as to the attributes of domains. Specific dimensions and their assignment to domains, as well as recommendations to guide future development, are discussed. PMID- 1634656 TI - Career commitment in nursing. AB - There are different patterns and styles to careers in nursing. The concept of career commitment in nursing is explored, and the results of some research are discussed for their implications for nursing careers. A longitudinal, repeated measures descriptive survey was used to measure career commitment and explore its relationship to turnover and work performance in 320 newly employed registered nurses at one hospital. Career commitment scores dropped significantly over the first year. Although career commitment does correlate with turnover, and there is a relationship with job performance, the direct association is weak. Career commitment is not a stable phenomenon in the first year in a new job. It appears to be susceptible to organizational factors, thus making it possible to provide positive benefits for both nurses and hospitals through enhanced career commitment. PMID- 1634657 TI - Nursing education administrators: level of career development and mentoring. AB - The focus of this study was to analyze the influence of mentoring on the level of career development of nursing education administrators. Other variables that may influence the level of career development of nursing education administrators also were examined. These included early life influences, academic preparation, supporting factors, constraining factors, and career stage. Relationships among these variables are depicted in the conceptual Model of Career Development in Academic Administration. Survey research methods were used in this correlational, retrospective study. A questionnaire developed by the investigators was mailed to a randomly selected national sample of 600 nursing education administrators in National League for Nursing-accredited baccalaureate and higher degree programs. A response rate of 71 per cent yielded 427 completed questionnaires. Multiple regression techniques were used to examine the relationships between dependent variables and independent variables in the conceptual model. Nine variables explained 59 per cent of the variance in level of career development scores. This variance was explained by highest degree earned, number of years since completion of the highest degree, number of years as an academic administrator, the scholarly difficulty index, the work commitment index, mentoring relationships, number of months of nonemployment, number of children, and type of institution where highest degree was earned. Mentoring contributed significantly to the prediction of level of career development of nursing education administrators and therefore should be encouraged and fostered. PMID- 1634658 TI - Nursing education: developing specification equations for selection and retention. AB - Because nursing is a professional area in which costs continue to rise faster than in other academic areas, it is imperative to provide quality education that is within the financial reach of those students who can benefit from it. This study sought to develop a specification equation that could be used to predict retention in the academic area and workplace. PMID- 1634659 TI - An analysis of the writings of Janet Geister and Mary Roberts regarding the problems of private duty nursing. AB - Fifty years ago there were two widely circulated nursing journals, each with a unique purpose and style. The Trained Nurse and Hospital Review was the privately owned older journal, and the American Journal of Nursing was the voice of the professional organization. Each journal was edited by a strong nursing leader, Janet Geister and Mary Roberts, respectively. Each editor had many years of service to the nursing profession in varied capacities. Naturally, each had distinctly different interests, visions, and styles of communication. These editors witnessed and commented on the change in the sphere of nursing practice from a private duty and public health orientation to one that eventually became dominated by the hospital. Although their approaches differed, both recognized the need for organization, versatility, and creative problem solving. However, the legacy of these leaders must be considered in view of the gap that continues to exist between practicing nurses and the American Nurses' Association leadership. PMID- 1634660 TI - Toward conceptualizations in nursing: harbingers from the sciences and humanities. AB - Conceptualizations of care and caring generated from ethnographic study of Tohono O'odham children, Norwegian-Americans, elderly clients in nursing clinics, preschoolers, children with cancer, and gender differences is outlined. Where research questions came from during life experiences of the author, a journey of nursing scholarship viewed from concepts of context development, transformation and care, and "Where do we go from here?" serve as the outline for a discussion of the generation of conceptualizations. A question for nursing research is proposed: What characteristics of care promote human responses for quality human experience? Suggestions for nursing research in the future emphasize the potential of human responses, variations in conceptualizations of care during the life cycles of human beings living in diverse cultural contexts, and changes in conceptualizations of care over time. PMID- 1634661 TI - Equivalence between adenosine and exercise thallium-201 myocardial tomography: a multicenter, prospective, crossover trial. AB - OBJECTIVES: The study was designed to compare pharmacologic and exercise stress during thallium-201 single-photon tomography in a multicenter prospective crossover trial. BACKGROUND: Both exercise and adenosine myocardial perfusion imaging have high sensitivity and specificity for detection of coronary artery disease. However, few data are available comparing these two stress tests in the same patients. METHODS: The study group consisted of 175 subjects: 55 healthy volunteers and 120 patients with suspected coronary artery disease. All subjects underwent two thallium tomographic tests performed 30 days apart, one during intravenous administration of adenosine (140 micrograms/kg per min for 6 min) and one during exercise stress. All images were computer quantified and interpreted without knowledge of the stress test performed. Interpretation agreement was assessed by kappa and Z statistics. RESULTS: Agreement on the presence of normal or abnormal tomograms by adenosine and exercise scintigraphy was 82.8% by visual analysis with kappa and Z statistics of 0.65 (p less than 0.0001) and 11.1 (p less than 0.00001), respectively. The agreement by computer quantification was 86% with kappa and Z statistics of 0.709 (p less than 0.0001) and 12.2 (p less than 0.00001), respectively. Agreement on localization of the perfusion defect to a specific coronary vascular territory varied from 82.7% to 91.4% with highly significant kappa and Z statistics (p less than 0.0001). There was a good correlation between quantified perfusion defect size by adenosine and exercise (r = 0.80, p less than 0.0001), but the values for defect size were significantly greater by adenosine scintigraphy (p = 0.0073). Adenosine side effects were frequent but transient and ceased spontaneously in most subjects within 1 to 2 min after the infusion was discontinued. CONCLUSIONS: Adenosine thallium-201 scintigraphy provides diagnostic information similar to that of exercise scintigraphy, although values for defect sizes are greater with adenosine. PMID- 1634662 TI - Effects of smoking on survival and morbidity in patients randomized to medical or surgical therapy in the Coronary Artery Surgery Study (CASS): 10-year follow-up. CASS Investigators. AB - OBJECTIVES: The goal of this study was to ascertain how continued cigarette smoking or smoking cessation related to long-term survival and morbidity in patients with established coronary artery disease managed with medical therapy or coronary bypass surgery. BACKGROUND: Although the association of cigarette smoking with coronary artery disease is well established, the morbidity and mortality associated with smoking behavior in patients with such disease receiving medical or surgical therapy are less well established. METHODS: The 780 patients randomized to medical therapy or coronary bypass surgery in the Coronary Artery Surgery Study (CASS) were subgrouped according to smoking behavior during a mean 11.2-year follow-up interval. Comparisons between smokers and nonsmokers were accomplished by univariate and Cox time-dependent multivariate analyses. RESULTS: Survival at 10 years after entry into the study was 82% among 468 patients who reported no smoking during follow-up (nonsmokers) compared with 77% among the 312 smokers (p = 0.025). Survival was 80% among those who smoked at entry but stopped (quitters) versus 69% among those who continued smoking (p = 0.025). For patients who smoked at baseline and were randomized to bypass surgery, survival at 10 years was 84% among quitters and 68% among nonquitters (p = 0.018); the difference in survival between quitters (75%) and nonquitters (71%) was less among those randomized to medical therapy (p = NS). Among those who smoked at baseline, continued smoking increased the relative risk of death by 1.73. After 10 years, smokers, in comparison with nonsmokers, were less likely to be angina free and more likely to be unemployed and had more activity limitation and more hospital admissions (primarily for chest pain, heart attack, cardiac catheterization, peripheral vascular surgery and stroke). CONCLUSIONS: Thus, among patients with documented coronary artery disease, continued cigarette smoking may result in decreased survival--especially among those undergoing bypass surgery. Moreover, smokers have more angina, more unemployment, a greater limitation of physical activity and more hospital admissions. PMID- 1634663 TI - Serial follow-up of adults with repaired tetralogy of Fallot. AB - OBJECTIVES AND BACKGROUND: Sudden death has long been considered a major contributor to mortality in pediatric patients with corrected tetralogy of Fallot. However, this may not apply to the patient with repaired tetralogy of Fallot who has survived into adulthood. Consequently we followed up a cohort of such adults to establish the clinical outcome and risk factors affecting their survival. METHODS: A baseline group of 151 adult patients with repaired tetralogy of Fallot were followed up for a mean of 3.2 years. The overall mortality rate was low (0.009 death/patient-year). Four patients died during follow-up, but only two deaths can be attributed to tetralogy of Fallot repair, and there were no sudden cardiac deaths. Clinically 94% of patients have remained in New York Heart Association functional class I. A subset of 36 patients were followed up for a mean of 6.7 years. This group had three sets of serial testing at 3-year intervals consisting of right heart catheterization at the initial study only, 24 h Holter ambulatory electrocardiographic (ECG) monitoring, exercise ECG and rest and exercise radionuclide angiography. RESULTS: Exercise capacity assessed by serial exercise stress testing remained stable over the follow-up period, whereas the presence of exercise-induced arrhythmias steadily decreased. Most patients had no significant arrhythmias and had no significant change in severity of arrhythmia with time. Radionuclide angiography showed significant improvement in exercise right ventricular ejection fraction over time but a progressive decrease in left ventricular ejection fraction at both rest and exercise. However, the left ventricular ejection fraction is still within the normal limits for our laboratory. CONCLUSIONS: Adults with repaired tetralogy of Fallot have a very good prognosis and a low risk of sudden death. However, ventricular function may change over time and should be carefully monitored. PMID- 1634664 TI - Prevalence and mortality rate of congestive heart failure in the United States. AB - OBJECTIVES: The study was designed to determine the prevalence and mortality rate of congestive heart failure in noninstitutionalized men and women in the U.S. BACKGROUND: Congestive heart failure is a serious condition with significant morbidity and mortality. Earlier epidemiologic descriptions of congestive heart failure were constructed from small surveys, limited data, hospital records or death certificates. No nationally representative data from noninstitutionalized persons have been examined. METHODS: Data collected from the National Health and Nutrition Examination Survey (NHANES-I, 1971 to 1975) were used to determine the prevalence of heart failure on the basis of both self-reporting and a clinical definition. Mortality data were derived from the NHANES-I Epidemiologic Follow-up Study (1982 to 1986). RESULTS: The prevalence of self-reported congestive heart failure approximates 1.1% of the noninstitutionalized U.S. adult population; the prevalence of congestive heart failure based on clinical criteria is 2%. These estimates suggest that between 1 and 2 million adults are affected. Mortality at 10 and 15 years for those persons with congestive heart failure increases in graded fashion with advancing age, with men more likely to die than women. In the group greater than or equal to 55 years old, the 15-year total mortality rate was 39.1% for women and 71.8% for men. CONCLUSIONS: Congestive heart failure is a common problem in the U.S., with significant prevalence and mortality, both of which increase with advancing age. As the population of the U.S. becomes older, the health care impact of congestive heart failure will probably grow. PMID- 1634665 TI - Effects of severity of the residual stenosis of the infarct-related coronary artery on left ventricular dilation and function after acute myocardial infarction. AB - OBJECTIVES: This study was designed to evaluate the relation between the severity of the residual stenosis of the infarct-related artery and changes in left ventricular volume and function after a first anterior myocardial infarction. BACKGROUND: Although thrombolytic therapy improves clinical outcome after acute myocardial infarction, the relations between the severity of the residual stenosis of the infarct-related artery and postinfarction left ventricular remodeling and function are unclear. METHODS: Fifty-eight patients with a first anterior myocardial infarction and significant disease only in the left anterior descending coronary artery on arteriography performed after 7 to 10 days were evaluated. All patients received thrombolytic therapy. Residual stenosis of the infarct-related artery was measured with quantitative coronary arteriography. Left ventricular volumes and ejection fraction were measured by echocardiography and radionuclide angiography, respectively, 7 to 10 days, 6 months and 1 year after infarction. End-diastolic and end-systolic left ventricular volumes were measured by two-dimensional echocardiography and normalized to body surface area. Patients were classified into three groups according to baseline residual stenosis severity: total occlusion (Group I), minimal lesion diameter less than 1.5 mm (Group II) and minimal diameter greater than or equal to 1.5 mm (Group III). RESULTS: Group I patients had significantly greater left ventricular end diastolic and end-systolic volumes at 6 months and 1 year than did the other groups. Group II patients had greater end-diastolic and end-systolic volumes than did Group III patients at 1 year. In addition, Group I patients had a lower ejection fraction at 1 year than that of the other groups. The minimal lesion diameter was significantly correlated with percent change in end-diastolic volume at 1 year. CONCLUSIONS: The severity of the baseline residual stenosis of the infarct-related artery is an important predictor of change in left ventricular volumes in the 1st year after infarction. Total occlusion of the infarct-related artery is associated with greater left ventricular dilation and functional impairment. PMID- 1634666 TI - Coronary angioplasty: a treatment option for left ventricular remodeling after myocardial infarction? PMID- 1634667 TI - Selection of patients for programmed ventricular stimulation: a clinical decision making model based on multivariate analysis of clinical variables. AB - OBJECTIVE: This study was conducted to assess the utility of clinical variables in predicting the inducibility of sustained ventricular arrhythmias in a heterogeneous group of patients undergoing programmed ventricular stimulation. METHODS: Variables were considered in a simulated chronologic order to determine the incremental information added by the signal-averaged electrocardiogram (ECG) and left ventricular ejection fraction. All patients undergoing baseline programmed ventricular stimulation for induction of ventricular tachyarrhythmia during a 30-month period were included in the study. Fourteen historical, ECG, signal-averaged ECG and left ventricular wall motion variables were evaluated for their ability in predicting inducibility of a sustained ventricular arrhythmia, a "positive" event, at programmed ventricular stimulation. RESULTS: On univariate analysis of the clinical variables, comparison between patients with positive or negative results showed significant differences in 10 of the 14 clinical variables: major cardiac diagnosis, history of ventricular tachycardia, myocardial infarction by history or ECG, all five signal-averaged ECG variables, left ventricular ejection fraction and presence of left ventricular aneurysm. On multivariate analysis, five independent variables were determined to be important: history of ventricular tachycardia, historical or ECG evidence of myocardial infarction, history of loss of consciousness, filtered QRS duration on the signal-averaged ECG and left ventricular ejection fraction. However, with sequential multivariate analysis, a model based only on historical and conventional ECG data was found to do as well as a model that included signal averaged ECG and left ventricular ejection fraction data. CONCLUSIONS: Routinely available noninvasive historical, ECG, signal-averaged ECG and left ventricular wall motion variables can be used to accurately predict the outcome of programmed ventricular stimulation. The majority of the predictive power was obtained with the routine model, using only historical and ECG data. The signal-averaged ECG and left ventricular wall motion analysis added no significant incremental information. PMID- 1634668 TI - Angiographic and clinical outcome of intracoronary stenting: immediate and long term results from a large single-center experience. AB - OBJECTIVES: The purpose of this study was to determine the immediate and long term angiographic and clinical results of coronary stenting. BACKGROUND: Although preliminary trials of endovascular stenting have demonstrated promising results, lack of long-term follow-up has limited the critical evaluation of the role of coronary stenting in the treatment of obstructive coronary artery disease. METHODS: A total of 250 procedures using the Palmaz-Schatz stent, performed in 220 patients between June 1988 and July 1991, were examined. Minimal lumen diameter of the treated segments was measured on angiograms obtained before, after and 6 months after intervention. RESULTS: Stent placement was successful in 246 (98%) of 250 lesions, reducing diameter stenosis from 77% to -2.5%. There were no deaths or Q wave myocardial infarctions. One patient (0.4%) required emergency bypass surgery and one (0.4%) developed subacute thrombosis. Femoral vascular complications occurred in 36 patients (16%). Six-month angiographic follow-up was obtained in 91% of eligible patients. The overall angiographic restenosis rate (stenosis greater than or equal to 50%) was 25%. By univariable analysis, the rate of restenosis was significantly higher for stents in the left anterior descending versus the right coronary artery (44% vs. 12%; p = 0.002); in diabetic patients (56% vs. 20%; p = 0.006), and in vessels with post-stent lumen diameter less than 3.31 mm (34% vs. 16%; p = 0.05). Stenting of the left anterior descending artery was the strongest predictor (p = 0.01) of restenosis in a multivariable model. Total survival was 97% and event-free survival (freedom from death, myocardial infarction or revascularization) was 70% at 36 months. CONCLUSIONS: Palmaz-Schatz stents can be placed successfully with a low incidence of major complications. The angiographic restenosis rate was 25%, and 70% of patients remained free of cardiovascular events at 3 years. Diabetes, small postprocedure lumen diameter and stenting of the left anterior descending artery are associated with higher rates of restenosis. PMID- 1634669 TI - Obstruction in extracardiac ventriculopulmonary conduits: value of nuclear magnetic resonance imaging with velocity mapping and Doppler echocardiography. AB - OBJECTIVES: This study was designed to investigate the value of noninvasive imaging modalities for the detection of obstruction in extracardiac ventriculopulmonary conduits. BACKGROUND: the diagnosis of obstruction in a conduit by noninvasive methods can be difficult. Obstruction may be silent and its progression unnoticed. Nuclear magnetic resonance imaging (NMR) with velocity mapping is a new noninvasive technique that can provide high resolution images and has been shown to be a reliable method of measuring blood flow velocity. METHODS: Two-dimensional echocardiography, pulsed wave Doppler echocardiography and NMR spin echo imaging were used in 52 patients with an extracardiac ventriculopulmonary conduit. Continuous wave Doppler echocardiography was used in 30 of these, Doppler color flow mapping in 26 and NMR velocity mapping in 12. Cardiac catheterization data were available in 27 patients and operative or autopsy findings in 11. RESULTS: The conduit could be assessed by two-dimensional and pulsed wave Doppler echocardiography in only 17% of patients. Doppler color flow and continuous wave echocardiography provided technically satisfactory data in 19% and 83%, respectively. The anatomy of the conduit was adequately displayed by NMR imaging in 90%. A minimal diameter less than 18 mm indicated conduit obstruction, although failure to detect calcification resulted in obstruction being missed in some patients. Calculated gradients in obstructed conduits derived from NMR velocity mapping correlated well with results of continuous wave Doppler echocardiography and gave an accurate localization of the site of obstruction as well as a measure of its severity. CONCLUSION: NMR imaging with velocity mapping is the most effective noninvasive method of assessing obstruction in ventriculopulmonary conduits and can obviate the need for invasive investigation before an interventional procedure is performed. PMID- 1634670 TI - Balloon pulmonary valvuloplasty in infants: a quantitative analysis of pulmonary valve-anulus-trunk structure. AB - OBJECTIVES: The present study was designed to establish possible predictors of unfavorable outcome in infants with pulmonary valve stenosis. BACKGROUND: Balloon pulmonary valvuloplasty is the treatment of choice for typical pulmonary valve stenosis. Patients with dysplastic valves may be less suitable candidates for this procedure because they have morphologic abnormalities of the complex valve anulus-trunk that cause the obstructive phenomenon. METHODS: Twenty-five children (mean age +/- SD 1.1 +/- 0.7 years) with normal anulus diameter underwent balloon pulmonary valvuloplasty using a balloon/anulus ratio of 1.2 +/- 0.11. From the lateral view of a right ventricular angiogram, the following variables were quantified and scored: A, supravalvular narrowing; B, texture of the valve surface; C, diastolic deformity of the Valsalva sinuses; D, trunk/anulus ratio; E, systolic valve motion; and F, presence of a contrast jet. Paired t test, stepwise multivariate correlation with "dummy" variable methods were applied for both hemodynamic and valve-anulus-trunk determinations. RESULTS: The right ventricular-pulmonary artery gradient decreased from 66 +/- 21 (range 40 to 120) to 24 +/- 11 (range 10 to 50) mm Hg (p less than 0.001), whereas the right ventricular systolic pressure decreased from 89 +/- 20 (range 60 to 130) to 48 +/ 15 (range 30 to 80) mm Hg (p less than 0.001). Only variables A, B and D had significant influence in a percent reduction in right ventricular pulmonary artery gradient (R2 0.94, SEE 5.7; p less than 0.001). A score greater than or equal to greater than 4 obtained by adding the values from these three variables was correlated with poor outcome. CONCLUSIONS: These data show that there is an adequate relation between scores and outcome. We conclude that children less than 2 years old with pulmonary valve stenosis and a score greater than or equal to 4 should not be candidates for balloon pulmonary valvuloplasty. PMID- 1634671 TI - Coronary artery abnormalities and right ventricular histology in hypoplastic left heart syndrome. AB - OBJECTIVES: To determine whether right ventricular preservation is compromised in any anatomic subgroup of hypoplastic left heart syndrome, we assessed the coronary artery anatomy and myocardial histologic features of 151 postmortem specimens with hypoplastic left heart syndrome. BACKGROUND: Although previous studies have shown that coronary artery abnormalities are more prominent in the subgroup of patients who have a patent mitral valve and obstructed aortic valve, it has not been established that these abnormalities compromise right ventricular perfusion. METHODS: Eighty-nine specimens with a patent mitral valve and aortic atresia, 52 with mitral and aortic atresia and 10 with patent mitral and aortic valves were examined. Histologic sections of the right ventricle, left ventricle and coronary arteries were obtained from 64 study hearts and 5 control hearts. RESULTS: Gross coronary anomalies included coronary-cameral communications (n = 29), single left coronary artery (n = 2), single right coronary artery (n = 1) and tortuosity (n = 19). Coronary-cameral communications and tortuosity were significantly associated with the subgroup that had mitral hypoplasia and aortic atresia. Coronary artery wall thickness relative to lumen diameter was not different among the subgroups. No areas of coronary artery stenosis or interruption were discovered. Although endocardial fibroelastosis of the left ventricle was strongly associated with the mitral hypoplasia and aortic atresia group, the right ventricular histologic findings were similar in all subgroups and were not differentially affected by older age. CONCLUSIONS: Although the incidence of coronary abnormalities is greater in patients with mitral hypoplasia and aortic atresia, in this study there was no apparent difference in perfusion of the right ventricle among the anatomic subgroups of hearts with hypoplastic left heart syndrome. PMID- 1634672 TI - Pulmonary circulation in pulmonary atresia associated with the asplenia cardiac syndrome. AB - OBJECTIVE: The goal of this study was to determine the patterns of the pulmonary circulation in patients with pulmonary atresia and asplenia. BACKGROUND: The asplenic cardiac syndromes characteristically have complex cardiac anomalies including pulmonary stenosis or atresia. Definition of the pulmonary artery circulation and pulmonary venous connections is needed for consideration of surgical procedures. METHODS: In 35 patients, the sources of pulmonary blood flow, anatomic features of pulmonary arteries and pulmonary venous connections were determined from angiograms or autopsy specimens. RESULTS: The main pulmonary artery was absent or hypoplastic in 91% of patients; most had a ductus arteriosus. The right and left pulmonary arteries were confluent in 90% and usually of normal size (right 71%, left 63%). Total anomalous pulmonary venous connections were present in 38%. CONCLUSIONS: The anatomic features of the pulmonary arteries in pulmonary atresia associated with the asplenic cardiac syndrome are usually favorable for palliative surgical procedures. Total anomalous pulmonary venous connection may exist as a complicating factor. PMID- 1634673 TI - Congenital aortic regurgitation: natural history and management. AB - OBJECTIVES AND BACKGROUND: Congenital aortic regurgitation is rare as an isolated lesion. We describe seven children with no physical features of the Marfan syndrome in the patients or their families and no other cardiac lesions who had congenital valvular aortic regurgitation. METHODS: From 1954 to the present, seven children with auscultatory and physiologic characteristics of aortic regurgitation were evaluated for a total of 108 patient-years. We report on their natural history, clinical and laboratory findings, management and outcome. RESULTS: In five of the seven children congenital aortic regurgitation was diagnosed in infancy. In four, progressive severity of the regurgitation led to valve replacement at age 3, 10, 15 and 20 years, respectively, and to resection of an aneurysm of the ascending aorta in the 10-year old patient. Two patients had cystic medial necrosis on aortic biopsy. One of these patients died after reoperation for dissecting aneurysm of the thoracic aorta at 22 years of age; the other died after dissection and rupture of the ascending aorta at age 25 years. After obstructing pannus developed, the 3-year old patient underwent replacement of the St. Jude valve at age 10 years. The other three patients were asymptomatic at last follow-up at age 8, 10 and 20 years, respectively. CONCLUSIONS: Supportive management is recommended until it becomes necessary to intervene surgically when regurgitation becomes severe. The need for surgical treatment is indicated by the appearance of a diastolic thrill, left ventricular strain on the electrocardiogram or other evidence of left ventricular dysfunction on the echocardiogram or exercise stress testing by treadmill or radionuclide cineangiocardiography. Close follow-up of these patients is important to detect progression of aortic regurgitation, especially in the presence of cystic medial necrosis. PMID- 1634674 TI - Intravascular stent prosthesis for right ventricular outflow obstruction. AB - OBJECTIVES: This study was designed to assess the impact of implantation of balloon-expandable stents on right ventricular outflow obstruction in children with congenital heart disease. BACKGROUND: Intravascular stenting has been established as a useful treatment in adults with coronary and peripheral vascular disease. Its application in the treatment of infants and children with pulmonary, systemic and right ventricular conduit obstruction resistant to balloon angioplasty is limited. METHODS: A total of 24 stainless steel stents were implanted in 17 patients. Five stents were placed within right ventricular to pulmonary artery conduits, 17 in branch pulmonary arteries and 1 in an aortopulmonary collateral vessel. Follow-up time has ranged from 1 to 14 months, with 6 patients having hemodynamic and angiographic studies greater than 1 year after stent placement. The mean age at implantation was 7.4 +/- 5.6 years and the mean weight 33 +/- 16 kg. RESULTS: Optimal stent position was obtained in 22 of 24 implantations. In one patient the stent slipped from the delivery balloon and was left positioned in the inferior vena cava. No embolization or thrombotic event has been documented. Among patients with right ventricular to pulmonary artery conduit obstruction, the gradient was immediately reduced from 85 +/- 30 mm Hg to 35 +/- 20 mm Hg after stent implantation; however, three patients required conduit replacement because of persistent obstruction with elevated right ventricular pressures (82 +/- 16 mm Hg). In 10 of 11 patients with pulmonary artery stenosis, clinical improvement was noted in association with enlargement of vessel diameter by 92% +/- 90% (range 17% to 355%) and the gradient reduction of 22 +/- 24 mm Hg to 3 +/- 4 mm Hg. CONCLUSIONS: These data support the view that intravascular stenting will become an important adjunct in the management of children with congenital heart disease. PMID- 1634675 TI - Rapid progression of aortic aneurysms after patch aortoplasty repair of coarctation of the aorta. AB - OBJECTIVES: This study was undertaken to evaluate the progression of aortic aneurysms after patch aortoplasty repair of coarctation of the aorta. BACKGROUND: Previous studies demonstrated a 5% to 25% incidence rate of repair site aneurysm 3 to 18 years after patch aortoplasty repair of coarctation. The natural history of aneurysmal progression in this disease entity has not previously been examined. METHODS: Twenty-nine patients were identified 5.6 +/- 1 years (mean +/- SE) postoperatively and classified into two groups: Group A, aneurysm (n = 7); Group B, no aneurysm (n = 22). The presence of an aneurysm was defined angiographically as a ratio of the repair site diameter to diaphragmatic aortic diameter (aortic ratio) greater than or equal to 1.5. A 23% prevalence (7 of 29) of aortic aneurysm was identified. One patient in Group A underwent semiemergency aneurysmectomy and two patients in Group B were lost to follow-up. The remaining 26 patients were reevaluated 3 to 5 years later by clinical examination and chest radiography. Aortograms were performed in all patients with suspected aneurysm formation or progression. RESULTS: Five of six patients in Group a demonstrated progressive aneurysmal dilation documented by an increase in aortic ratio from 1.64 +/- 0.06 to 2.04 +/- 0.2 (p = 0.03) and an increase in absolute aneurysm diameter from 2.5 +/- 0.3 to 3.6 +/- 0.5 cm (p = 0.006). Only 1 of 20 patients in Group B had evidence of new aneurysmal dilation (p less than 0.05 vs. Group A). Four patients in Group A have undergone elective aneurysmectomy, with equal distribution of true and pseudoaneurysms by pathologic examination. CONCLUSIONS: Aortic aneurysm formation is common after patch aortoplasty repair of coarctation of the aorta. The majority of patients with an aortic ratio greater than or equal to 1.5 will show significant progressive aneurysmal dilation within 3 to 5 years. PMID- 1634676 TI - Fixed subaortic stenosis in atrioventricular canal defect: a Doppler echocardiographic study. AB - OBJECTIVES: The objectives of this retrospective study were to describe the Doppler and echocardiographic features of fixed subaortic stenosis in the setting of atrioventricular (AV) canal defect and to document the de novo occurrence of subaortic stenosis and progression of this lesion over time on the basis of sequential echocardiographic studies. BACKGROUND: The coexistence of fixed subaortic and AV canal defect has been sporadically noted, but no single or multicenter experience with this constellation of abnormalities has been previously described. METHODS: All patients with a diagnosis of subaortic stenosis and complete or partial AV canal defect who had one or more Doppler echocardiographic examinations were identified from a computer data bank. Retrospective analysis was performed, including review of patients' charts, operative notes, recorded videotapes and hard copy recordings when available. RESULTS: Twenty-one patients with both subaortic stenosis and AV canal defect were identified over a 13-year period. Fifteen were female and the mean age at diagnosis of subaortic stenosis was 16 years. Fifteen patients had partial AV canal defect with prior repair in 10; 6 patients had complete AV canal defect with prior repair in 4. The mean interval from prior repair to recognition of subaortic stenosis was 6.8 years. In six patients, serial examinations demonstrated the de novo occurrence of subaortic obstruction over a period of 10 to 87 months. In five patients, progression of known subaortic stenosis was documented over a 10- to 59-month period. Surgical resection of subaortic stenosis was performed in 16 patients; the echocardiographic diagnosis was confirmed in 15 of the 16. CONCLUSIONS: In the largest reported echocardiographic series of this lesion complex, it is concluded that subaortic stenosis can occur de novo, is often recognized only after repair of the canal defect and is progressive. Doppler echocardiography is the method of choice for diagnosis and serial follow-up of these patients. PMID- 1634677 TI - Steroid-eluting epicardial pacing leads in pediatric patients: encouraging early results. AB - OBJECTIVES: This study evaluated the pacing and sensing characteristics of a new porous-tipped steroid-eluting epicardial lead in a group of pediatric patients. BACKGROUND: Pacing in children may be complicated by small patient size, patient growth and the prevalence of structural congenital heart disease in children requiring pacing. Epicardial pacing has been associated with a high incidence of problems with sensing and capture, prompting the use of transvenous endocardial pacing when possible. In some children, epicardial pacing may still be desirable because of small patient size, potential for caval obstruction, previous cardiac surgery limiting transvenous access to the heart, or the need to repair congenital heart disease at the time of pacemaker insertion. METHODS: Twelve patients aged 3 weeks to 18 years underwent placement of 23 epicardial pacing leads (8 atrial, 15 ventricular). Pulse width thresholds, sensing thresholds and lead impedance were measured weekly for 6 weeks, then at 3, 6, 12 and 18 months after pacemaker implantation. The median duration of follow-up was 12 months. RESULTS: Ventricular pulse width thresholds did not change over time, whereas atrial pulse width thresholds improved significantly. At 6 months, the mean pulse width threshold at 2.5 V for the atrial and ventricular leads was 0.10 +/- 0.03 and 0.19 +/- 0.09 ms, respectively. The thresholds were slightly lower at 12 and 18 months. At the most recent follow-up, all atrial leads sensed appropriately at 2.5 mV and all ventricular leads at 5 mV. CONCLUSIONS: These encouraging early results suggest that steroid-eluting epicardial pacing leads may be an attractive option for children needing epicardial pacing. Their excellent pacing and sensing characteristics may allow reliable dual-chamber pacing in infants who are too small for transvenous pacing. PMID- 1634678 TI - Simultaneous measurement of coronary flow reserve by left anterior descending coronary artery Doppler and great cardiac vein thermodilution methods. AB - OBJECTIVES: The objective of this study was to compare left anterior descending coronary artery Doppler blood flow velocity and great cardiac vein thermodilution blood flow measurements of coronary flow reserve and submaximal coronary vasodilation in humans. BACKGROUND: Reported maximal coronary flow reserve values obtained with the coronary venous thermodilution method are lower than those obtained with other measurement methods. METHODS: Thermodilution measurements of great cardiac vein flow in 11 subjects were compared with simultaneous Doppler measurements of changes in left anterior descending coronary flow velocity after intracoronary administration of papaverine, nitroglycerin, iohexol and intravenous administration of dipyridamole. RESULTS: Coronary flow reserve (papaverine peak/rest flow ratio) was 3.7 +/- 1.7 (mean +/- SD) by the Doppler method and 2.0 +/- 0.7 by the thermodilution technique (p less than 0.001). Thermodilution flow changes were also smaller than Doppler-measured changes during submaximal vasodilation and during prolonged coronary dilation after dipyridamole administration. CONCLUSIONS: Coronary flow reserve and submaximal flow increases measured with the thermodilution method were consistently and substantially smaller than Doppler-derived measurements. This discrepancy has important implications for the comparison of coronary flow reserve measurements performed with the use of different techniques. PMID- 1634679 TI - Etiology of the Austin Flint murmur. AB - OBJECTIVES: The aim of the study was to determine the mechanism of the Austin Flint murmur. BACKGROUND: More than 100 years after the initial description of the Austin Flint murmur, the etiology of the murmur remains unclear. METHODS: M mode and two-dimensional echocardiography, conventional and color flow Doppler study, and cine nuclear magnetic resonance (cine NMR) imaging were performed in 24 patients with clinically moderate or severe aortic regurgitation. Mitral valve area was determined by planimetry and pressure half-time measurement. Overlap of the aortic regurgitation and mitral inflow jets was graded 0 (no overlap) to 4 (marked overlap) by Doppler study and cine NMR imaging. The volume of signal loss resulting from turbulent blood flow secondary to the aortic regurgitation jet was determined on cine NMR images, and the extent of contact with the left ventricular endocardium was graded 0 (no contact) to 4 (extensive contact). RESULTS: The presence of an Austin Flint murmur did not correlate with mitral valve area (2.7 +/- 0.8 cm2 with the murmur vs. 2.5 +/- 0.7 cm2 without), overlap of the aortic regurgitation and mitral flow jets (3 +/- 1 vs. 2.3 +/- 1.2), diastolic mitral regurgitation (50% vs. 71%) or fluttering of the anterior mitral valve leaflet (70% vs. 50%). The presence of an Austin Flint murmur correlated best with the volume of signal loss associated with the aortic regurgitation jet on cine NMR imaging (65 +/- 16 ml with the murmur. vs. 38 +/- 11 ml without, p less than 0.001) and the extent of contact of this signal loss with the left ventricular endocardium (2.9 +/- 0.5 vs. 1.5 +/- 0.4, p less than 0.0001). CONCLUSIONS: The Austin Flint murmur is caused by the aortic regurgitation jet abutting the left ventricular endocardium, resulting in the generation of a low pitched diastolic rumbling. PMID- 1634680 TI - Nature and time course of generation of isoforms of creatine kinase, MB fraction in vivo. AB - OBJECTIVES: This study was designed to characterize the nature and time course of carboxy-terminal lysine cleavages from the tissue isoform of MB creatine kinase (CK) in vivo. BACKGROUND: Rapid conversion of the tissue isoform of MM CK to two additional circulating isoforms with one or both carboxy-terminal lysines cleaved facilitates early detection of new tissue isoform release after acute myocardial infarction and coronary recanalization. Characterization of changes in plasma MB CK isoform profiles, potentially enhancing specificity even further, has been hindered by difficulties in separating the isoform products and elucidation of carboxy-terminal lysine cleavages underlying their formation. METHODS: Isoform species with carboxy-terminal lysine present on B-monomers were separated from those from which lysine had been cleaved by anion exchange chromatography. Carboxy-terminal lysine on M-monomers was assayed with the use of a monospecific antibody. RESULTS: MB CK in four pooled plasma samples from among 77 normal subjects exhibited carboxy-terminal lysine on 48 +/- 21% (mean +/- SEM) of B monomers and 82 +/- 12% of M-monomers. Within the 1st 16 h after the onset of acute myocardial infarction, virtually all M- and B-monomers exhibited carboxy terminal lysine, indicating release into plasma and the lack of rapid cleavage of lysine from the tissue isoform. After 20 to 30 h, 43 +/- 9% (three pools from 19 patients) of B-monomers and 95 +/- 10% of M-monomers exhibited lysine at the carboxyl terminus. After 40 to 50 h, 13 +/- 13% (four pools from 34 patients) of B-monomers and 46 +/- 19% of M-monomers still retained carboxy-terminal lysine. CONCLUSIONS: In contrast to MM CK, the tissue isoform of MB CK undergoes slow cleavage of lysine from both monomers in vivo. Sequential cleavage of lysine first from the carboxyl terminus of B-monomers and subsequently from M-monomers is consistent with generation of at least two additional isoforms. Development of assays capable of resolving all of the isoforms of MB CK that can occur in vivo might increase sensitivity for early detection of new tissue isoform release associated with acute myocardial infarction and coronary recanalization compared with currently available assays that resolve only two species. PMID- 1634681 TI - Left ventricular flow propagation during early filling is related to wall relaxation: a color M-mode Doppler analysis. AB - OBJECTIVES: This study was designed to evaluate the relation between the velocity of flow propagation and left ventricular relaxation by using color M-mode Doppler echocardiography to analyze flow propagation in the left ventricle. BACKGROUND: Noninvasive attempts to identify alterations in left ventricular relaxation have been hampered because both the relaxation rate and left atrial filling pressure are the determinants of peak early velocity and filling rate. METHODS: Color M mode velocity data were transferred to a microcomputer and compared with conventional pulsed Doppler data to assess the ability of color M-mode echocardiography to analyze velocity field properties. The velocity of flow propagation was measured as the slope of the flow wave front during early filling in normal subjects (n = 29) and in patients with disease that alters relaxation (dilated cardiomyopathy [n = 31], ischemic cardiomyopathy [n = 8], hypertrophic cardiomyopathy [n = 5], systemic hypertension [n = 22] and aortic valve disease [n = 25]). In nine patients with end-stage dilated cardiomyopathy, echocardiographic and left heart catheterization data were obtained at baseline and during intracoronary dobutamine infusion. RESULTS: Color M-mode and pulsed Doppler echocardiographic data were highly correlated (n = 217, r = 0.94, p less than 0.0001, velocity range 0.2 to 1.5 m/s). The velocity of flow propagation was lower in patients than in normal subjects (0.46 +/- 0.15 vs. 0.84 +/- 0.11 m/s, p less than 0.0001). The decrease was significant in all disease forms with or without left ventricular dilation. The velocity of flow propagation was related to peak early velocity in normal subjects (p less than 0.001) but not in patients. It varied inversely with the isovolumetric relaxation time constant during dobutamine infusion and the two variables were highly correlated (p less than 0.0001). CONCLUSIONS: The velocity of flow propagation during early filling seems to be highly dependent on the left ventricular relaxation rate and could be an important tool in studying diastolic function. PMID- 1634682 TI - Variability in the quantitation of mitral regurgitation by Doppler color flow mapping: comparison of transthoracic and transesophageal studies. AB - OBJECTIVES: This study was designed to assess the most accurate and reproducible methods to quantitate mitral regurgitation by color flow transthoracic and transesophageal echocardiography. BACKGROUND: Quantitative measurements of mitral regurgitant jets have resulted in an intraobserver and interobserver variability of up to 20%. Few data are available evaluating the various techniques by which mitral regurgitant jets are quantitated. METHODS: Forty patients who underwent cardiac catheterization and both transesophageal and transthoracic echocardiography within 1 week were studied. Two boundaries of the color regurgitant jet area were identified and quantitated: 1) the central aliased core of the regurgitant jet with the mosaic pattern excluding any swirling low velocity flow; and 2) the largest definable area of the regurgitant flow, including low velocity flow considered to be part of the regurgitant jet. RESULTS: The total regurgitant areas obtained by transthoracic and transesophageal studies did not differ (5.7 +/- 4.6 vs. 5.7 +/- 3.7 cm2; p = NS). However, the transesophageal mosaics were significantly larger than those obtained by transthoracic echocardiography (3.6 +/- 3.1 vs. 2.8 +/- 3.4 cm2; p less than 0.01). In transthoracic studies observer variability was higher when the mosaic aspect of the regurgitant jet rather than the total regurgitant area was measured (24 +/- 20 vs. 16 +/- 11%; p less than 0.05). In contrast, in transesophageal studies variability was lower when the mosaic area rather than the total regurgitant area was measured (11 +/- 12% vs. 18 +/- 18%; p less than 0.05). The best correlations with left ventriculography were obtained by using the absolute total regurgitant area (r = 0.72) for transthoracic studies and the mosaic area of the jets (r = 0.87) for transesophageal studies. CONCLUSIONS: Doppler color flow jet areas correlate closely with angiographic results in the evaluation of mitral regurgitation. The total regurgitant area (including the surrounding swirling flow) in transthoracic studies and the aliased core of the regurgitant jet (mosaic) in transesophageal studies appear to be the most accurate and reproducible measurements for evaluating mitral regurgitation. PMID- 1634683 TI - Quantitation of Doppler color flow recordings: an oxymoron? PMID- 1634684 TI - Activation patterns in experimental canine atrial flutter produced by right atrial crush injury. AB - OBJECTIVES: This study was designed to localize and characterize the atrial flutter reentrant circuit and the electrophysiologic effects of right atrial crush injury in a new canine model. BACKGROUND: In previous studies sustained atrial flutter was induced in the canine heart by rapid atrial pacing after a linear crush injury was placed in the right atrial free wall. METHODS: Eight dogs (group 1) with three electrode plaques on the right and left atria and Bachmann's bundle and seven dogs (group 2) with a single high density electrode plaque on the right atrium were studied with use of a 64-channel computerized mapping system. RESULTS: At baseline, during sinus rhythm and right and left atrial pacing, activation spread uniformly without areas of slow conduction. Crush injury produced marked conduction delay or complete block during sinus rhythm, increasing the mean difference in activation times across the injury compared with control values (group 1, 31 +/- 4 vs. 14 +/- 5 ms, p less than 0.01; group 2, 28 +/- 10 vs. 7 +/- 2 ms, p less than 0.01). Rapid atrial pacing (S1S1 200 ms) above and below the crush injury revealed a line of complete block across which adjacent electrodes recorded markedly different activation times (33 +/- 5 and 38 +/- 12 ms difference, respectively) and around which activation wave fronts proceeded, colliding opposite the stimulating electrodes. The mean atrial flutter cycle length of 11 episodes induced in group 1 and 14 episodes in group 2 was 157 +/- 16 and 140 +/- 16 ms, respectively (p = NS). Activation mapping revealed a reentrant circuit in the right atrium around the crush injury in all episodes. Although the reentrant circuit did not contain a discrete area of slow conduction, activation time below was longer than that above the crush injury (92 +/- 14 vs. 66 +/- 8 ms and 82 +/- 12 vs. 59 +/- 9 ms in groups 1 and 2, respectively, p less than 0.01 for both). Rapid atrial pacing or premature stimuli produced progressive conduction delay and unidirectional block between the crush injury and the tricuspid anulus, inducing atrial flutter directly in 9 of 25 episodes. In 16 episodes, atrial flutter developed after transient induction of atrial fibrillation. CONCLUSIONS: 1) Atrial flutter in this model is due to reentry in the right atrium; 2) the crush injury functions as an anatomic obstacle around which reentry may occur; and 3) the reentrant circuit does not contain a discrete area of slow conduction but, rather, generally slower conduction below the crush injury. PMID- 1634685 TI - Short-term administration of estrogen and vascular responses of atherosclerotic coronary arteries. AB - OBJECTIVES: This experiment sought to determine the effect of short-term administration of estrogen on endothelium-dependent dilation in the coronary arteries of 13 surgically postmenopausal female cynomolgus monkeys. BACKGROUND: Long-term estrogen replacement therapy prevents impaired endothelium-dependent dilation of atherosclerotic coronary arteries in postmenopausal female monkeys. However, it remains unclear whether this action of estrogen is due to long-term effects on plasma lipids and atherogenesis or to direct short-term effects on the endothelium. METHODS: The monkeys consumed an atherogenic diet for 18 months after bilateral ovariectomy. Vascular responses were measured just before euthanasia and necropsy. Dextrose in water (control), acetylcholine, 10(-6)M, and nitroglycerin were infused for 2.5 min each both before and 20 min after intravenous injection of 54 ng ethinyl estradiol. RESULTS: Quantitative coronary angiography revealed that the arteries constricted (-17 +/- 3%) in response to intracoronary infusion of acetylcholine before estrogen treatment but dilated (+5 +/- 3%) 20 min after intravenous injection of ethinyl estradiol (p less than 0.05). Coronary arteries dilated in response to nitroglycerin both before and after administration of estrogen (p greater than 0.05). Vascular responses of coronary arteries, both before and after administration of estrogen, were not associated with variation in plasma lipid concentrations, blood pressure, heart rate or plaque size. CONCLUSIONS: Estrogen affects endothelium-dependent coronary dilation within 20 min of administration and may have rapid direct effects on the vascular endothelium. PMID- 1634686 TI - Reversal of acetylcholine effect on atherosclerotic coronary arteries by estrogen: pharmacologic phenomenon of clinical importance? PMID- 1634687 TI - Coronary intimal proliferation after balloon injury and stenting in swine: an animal model of restenosis. AB - OBJECTIVES: This study was designed to compare the proliferative response in coronary arteries after tantalum stent placement or balloon injury in a normolipemic swine model of restenosis. BACKGROUND: Restenosis remains a significant complication of percutaneous transluminal coronary angioplasty. Efforts to study restenosis have been hampered by the lack of a suitable animal model. METHODS: In an attempt to create lesions resembling those of human restenosis, normolipemic swine underwent injury of either the left anterior descending or the left circumflex coronary artery with either balloon inflation or deployment of a tantalum stent. At 4 weeks, they were killed and the injured vessels processed for histopathologic analysis. Intimal area, lumen area and maximal intimal thickness were measured. The degree of stenosis was expressed as residual lumen area (lumen area/intimal area ratio). RESULTS: Vessels injured by either method demonstrated significant intimal smooth muscle proliferation leading to reduction in lumen area. In the 18 stented vessels residual lumen area measured 0.64 +/- 0.18 and maximal intimal thickness measured 0.6 +/- 0.3 mm; in the 15 balloon-injured vessels these values were 0.75 +/- 0.18 and 0.4 +/- 0.3 mm, respectively (p less than 0.05). In addition, most stented vessels had reactive inflammatory infiltrates surrounding the stent wires composed of lymphocytes, histiocytes and many eosinophils. CONCLUSIONS: These data indicate that coronary artery injury in swine with either balloon inflation or stenting leads to intimal smooth muscle cell proliferation similar to that seen in human restenosis. The degree of intimal proliferation appears to be greater after stenting than after balloon injury. Intracoronary stenting in swine is associated with a marked inflammatory reaction around the stent wires. These models may be helpful in planning systemic and local antirestenosis strategies. PMID- 1634688 TI - Electrocardiogram of the humpback whale (Megaptera novaeangliae), with specific reference to atrioventricular transmission and ventricular excitation. AB - OBJECTIVES: The objective of the study was to record the electrocardiogram (ECG) of a large whale to obtain crucial data for comparative electrophysiologic analysis. BACKGROUND: The data were needed to establish the mismatch between heart size and PR interval and QRS duration in mammals. METHODS: In the waters off the coast of Newfoundland, in two humpback whales (Megaptera novaeangliae) with an estimated weight of 30,000 kg a 1-lead ECG was recorded, enabling reliable assessment of P waves and QRS complexes. RESULTS: It was found that both the PR interval (atrioventricular [AV] transmission time) and QRS duration (ventricular excitation) are extremely short for animals of this size. These findings are difficult, if not impossible, to explain on the basis of currently accepted electrophysiologic theories. However, the narrow QRS complex may be due to a very dense His-Purkinje network in the ventricular wall of whales. Alternative mechanisms that can explain the function of the mammalian AV node need to be considered and explored. CONCLUSIONS: The results of the study may be of value for the understanding of the ECG in humans. PMID- 1634689 TI - Transcoronary chemical ablation of ventricular tachycardia in chronic chagasic myocarditis. AB - OBJECTIVE: A case of incessant ventricular tachycardia in a patient with Chagas' disease that was successfully terminated by chemical ablation is reported. BACKGROUND: Chagas' disease is a common medical problem in South America. Ventricular tachyarrhythmias, atrioventricular conduction disturbances, congestive heart failure and sudden cardiac death are important manifestations of this disease. METHODS: Selective catheterization of the coronary artery supplying the arrhythmogenic area was performed by using a conventional angioplasty system and the arrhythmogenic area was ablated by injection of 96% sterile ethanol. RESULTS: Ethanol (96%) injection initially in a lateral branch of the left circumflex artery and 2 days later in the proximal segment of the artery resulted in termination of ventricular tachycardia. Two weeks after ablation, programmed ventricular stimulation failed to induce ventricular tachycardia. CONCLUSION: Transcoronary chemical ablation should be considered in selected cases of Chagas' disease with incessant ventricular tachycardia. PMID- 1634690 TI - Cardiac alternans: diverse mechanisms and clinical manifestations. AB - OBJECTIVES: The purpose of this review is to assemble the widely dispersed information about cardiac alternans and to categorize the types and mechanisms of alternans, their clinical manifestations and possible therapeutic implications. BACKGROUND: The phenomena of mechanical and electrical alternans have been of continuing interest to both physiologists and clinicians. Recent studies have enhanced this interest because of the reported association of alternans with experimental myocardial ischemia and cardiac arrhythmias. METHODS: The review formulates concepts based on extensive review of published studies and personal observations. RESULTS: Cardiac alternans has been subdivided into the following four categories: 1) mechanical, 2) electrical, 3) in association with myocardial ischemia, and 4) in association with cardiac motion. Mechanical alternans can be explained by hemodynamic or inotropic alterations, or both. Mechanical alternans in the ventricular muscle is accompanied by alternans of action potential shape. In the Purkinje fibers, action potential duration alternates without change in shape and is determined by the duration of the preceding diastolic interval. However, in ventricular muscle fiber, alternans can occur in the presence of constant diastolic intervals. T wave alternans reflects changes in action potential duration and is frequently associated with a long QT interval. Electrocardiographic manifestations of conduction alternans occur at many different sites within the conducting system and myocardium. During myocardial ischemia, additional mechanisms of repolarization alternans have been proposed. Alternans occurring in the presence of a large pericardial effusion is attributed to swinging motion of the heart maintaining two-beat periodicity. CONCLUSIONS: Since its origin as "pulsus alternans" described by Traube in 1872, the definition of alternans has evolved into a term encompassing multiple physiologic and pathologic phenomena that, although united by the term cardiac alternans, diverge widely with respect to etiology, mechanism and clinical significance. PMID- 1634691 TI - The long QT syndrome: a G or not a G? PMID- 1634692 TI - Transesophageal echocardiography. American College of Cardiology position statement. PMID- 1634693 TI - Marital coital activity in men at the age of 75: relation to somatic, psychiatric, and social factors at the age of 70. AB - OBJECTIVE: To find somatic, psychiatric, and social variables that predicted cessation of coital activity in elderly married men. DESIGN: Prospective, longitudinal, observational study SETTING: General survey of a representative sample of 70-year-old urban men (born in 1901-02) in Goteborg, Sweden. PARTICIPANTS: Forty-one men who were married and had coital activity at age 70 and who, at the age of 75, were still married when the sample was reinterviewed. MAIN OUTCOME MEASURES: Presence (c) or absence (nc) of coital activity at age 75. RESULTS: Cessation of coital activity was associated with vasculogenic factors. At least one of the following disorders--systemic hypertension, ischemic heart disease, congestive heart failure, diabetes mellitus, or hypertriglyceridemia- was found in three of the C men and 14 of the NC men, P less than 0.005. Systemic hypertension was the most common disorder and was found in one C man and 10 NC men, P less than 0.01. Cessation of coital activity was associated with specified types of stress between 65 and 70 years of age in the subgroup of men who had stopped due to inability; six out of eight reported stress against five out of 20 in the C group, P less than 0.05. There was no association with any of the psychiatric or social factors studied. CONCLUSIONS: Cessation of coital activity is predicted by somatic disorders which are associated with vascular damage and especially by hypertension. This observation does not allow the conclusion that antihypertensive treatment would be effective in postponing the cessation of coital activity. PMID- 1634694 TI - The relationship of patient's age to the perceptions of the rehabilitation environment. AB - OBJECTIVE: To compare the perceptions of the rehabilitation environment among staff, younger (less than 65), and older patients (greater than 65). DESIGN: The Ward Atmosphere Scale (WAS) was administered to 55 patients and 108 staff members in a rehabilitation hospital. SETTING: A large university-associated free standing rehabilitation hospital. SUBJECTS: Patients and staff primarily associated with one of three treatment teams, each on a separate floor. The teams were selected to reflect a diversity of treatment styles and patients' diagnoses. MAIN OUTCOME MEASURE: The WAS is a 100 true/false questionnaire with 10 subscales which combine to form three dimensions: relationship, program orientation, and system maintenance. These dimensions represent the principal constructs of the instrument. MAIN RESULTS: Multivariate analysis of variance was performed on three groups completing the WAS--staff, patients less than 65 years old, and patients 65 years and older. This analysis revealed significant differences among the three groups on the Relationship (F = 14.3; P less than 0.01) and Program Dimensions (F = 36.5; P less than 0.01), and between staff and patients on the System Maintenance Dimension (F = 11.4; P less than 0.01). Compared to younger patients and staff, older patients had lower perceptions in the combined areas of involvement, support, spontaneity, autonomy, practical orientation, personal problem orientation, and anger and aggression. Likewise, older patients perceived more staff control than staff and younger patients. Younger patients scored between older patients and staff. CONCLUSIONS: This study suggests that there may be a mismatch between current rehabilitation environments and the needs of elderly individuals. PMID- 1634695 TI - The Test for Severe Impairment: an instrument for the assessment of patients with severe cognitive dysfunction. AB - OBJECTIVE: To develop a reliable and valid test of cognitive function suitable for patients with severe cognitive impairment. DESIGN: Administration of a test; test-retest reliability; comparison to traditional test. SETTING: Chronic long term-care facility. PATIENTS OR OTHER PARTICIPANTS: The participants were 40 elderly residents with severe cognitive impairment. MAIN OUTCOME MEASURES: Results of the Test for Severe Impairment (TSI) and its subsections (language, memory, executive function, and motor performance); correlation of test and retest scores; correlation of TSI with Mini-Mental State Exam. RESULTS: The TSI was significantly correlated with the Mini-Mental State Exam (r = 0.83, P less than or equal to 0.0001). Test-retest reliability was high (r = 0.96, P less than 0.0001). The internal reliability of the test was also good (alpha = 0.90). Preliminary result of a factor-analysis suggests that factor scores may be derived that relate to memory, language production, and knowledge of body parts. CONCLUSIONS: The TSI is a valid and reliable test of cognitive function in patients with severe cognitive impairment. It is appropriate to use it as a unified scale. PMID- 1634696 TI - Occult elevation of CK as a manifestation of rhabdomyolysis in the elderly. AB - OBJECTIVE: To evaluate the incidence, etiology and clinical course of rhabdomyolysis in hospitalized elderly patients. DESIGN: Retrospective case series. SETTING: Acute geriatric department of a university-affiliated teaching hospital. PATIENTS: Twenty-three patients who fulfilled our criteria of rhabdomyolysis. Criteria for inclusion were the finding of elevated serum creatine kinase of five-fold or greater above the upper reference limit and greater than 97% MM isoenzyme. RESULTS: In a 3-year period 23 patients out of 2,870 admissions fulfilled the criteria for rhabdomyolysis, an incidence rate of 0.8%. Diseases or insults associated with rhabdomyolysis were, in order of frequency, acute immobilization, infectious disease, cerebrovascular accident, hyperosmolar state, hyponatremia, hypernatremia, hypothermia, and a fall. Twenty two patients recovered from the acute illness; one patient died from respiratory failure. Seventeen patients had renal failure (serum creatinine greater than 180 mumol/L), none necessitating dialysis. Serum creatinine always declined following recovery. CONCLUSION: Elevation of CK with few other clinical features of rhabdomyolysis is common in admissions to a geriatric service. It is due to complete immobilization resulting from acute illness. Renal failure is mild and reversible, and the prognosis for recovery is excellent. PMID- 1634697 TI - Measurement of activities of daily living in hospitalized elderly: a comparison of self-report and performance-based methods. AB - OBJECTIVE: To determine the accuracy of self-reports of physical functioning by hospitalized elderly. DESIGN: Comparison of two measures. PATIENTS AND SETTING: Two-hundred forty-seven medical inpatients (mean age 78.7 years) hospitalized at St. Marys Hospital Medical Center, Madison, WI. MAIN OUTCOME MEASURES: Measures of five activities of daily living by self-report and by performance. RESULTS: The rate of agreement between self-report and performance ADL measures was the lowest in the areas of bathing and dressing where the agreement was 63% and 64%, respectively. When patients reported needing no help in these two tasks, they were measured lower 32% of the time for dressing and 42% for bathing. When patients reported needing help in an activity the agreement rate between patient and occupational therapist varied widely, from only 42% for toileting to 78% for bathing. The two factors which were statistically associated with poor agreement between the two ADL measurements were cognitive impairment (P less than 0.001) and a decline from the pre-hospital level of ADL functioning which had occurred during hospitalization (P less than 0.001). CONCLUSIONS: These data suggest that there may be significant differences between patient assessments and performance based measurements of ADL functioning in hospitalized elderly at time of discharge. These differences may have implications for the collection of functional measurements for discharge planning or for geriatric research in the hospital environment. PMID- 1634698 TI - The Caretaker Obstreperous-Behavior Rating Assessment (COBRA) Scale. AB - OBJECTIVE: To evaluate the usefulness and reliability of the Caretaker Obstreperous-Behavior Rating Assessment (COBRA), a new test instrument for caretaker assessment of types and severity of "obstreperous behaviors" (OBs) in demented patients. DESIGN: COBRA was completed by caretakers of 31 outpatients and 36 nursing home inpatients with dementia. Test-retest reliability was determined when 25 of the outpatient caretakers re-evaluated their demented relative 1 week later; inter-rater reliability was determined on nursing home inpatients by comparing the reports of two nurse's aids with equivalent knowledge of seven of the patients. SETTING: (1) University medical center Alzheimer's Disease and Related Disorders Clinic; (2) community nursing home. PATIENTS: Thirty-one sequentially-seen outpatients with dementia; 36 nursing home patients with dementia. INTERVENTION: Following instruction in the use of the COBRA Scale, caretakers provided scores for their demented patient. The instrument has three unique features: (1) it divides OBs into four categories for ease of comprehension: Aggressive/Assaultive; Mechanical/Motor; Ideational/Personality; and Vegetative; (2) a companion videotape shown to caretakers in advance illustrates each behavior to improve reliability of reporting; (3) the significance of each OB is estimated with severity and frequency measures. MAIN OUTCOME MEASUREMENTS: Frequency and severity of OBs are epitomized in 12 summary scores. Test-retest correlations (for outpatients) and inter-rater correlations (for inpatients) were analyzed with Pearson Product Moment and Spearman Rank Order correlations. RESULTS: Prevalence of OBs and severity was reported for the experimental groups. Summary scores revealed test-retest correlations of .95 to .73 for 11 of 12 scores (outpatients), and inter-rater correlations of .99 to .73 for 8 of 12 scores (inpatients). Age, gender, and disease etiology were not significantly related to OBs; clinical severity correlated with type and severity of OBs. CONCLUSIONS: The COBRA scale provides a convenient, comprehensive, and reliable means for caretakers to identify the types and measure the severity of OBs in demented outpatients and nursing home inpatients. If additional studies confirm these observations, COBRA will be a useful instrument for assessing the effects of interventions on OBs in patients with dementia. PMID- 1634699 TI - The physician's decision to use tube feedings: the role of the family, the living will, and the Cruzan decision. AB - OBJECTIVE: To determine the relative importance of factors influencing physicians to use tube feedings in patients lacking decision-making capacity. DESIGN: Survey. SETTING AND PARTICIPANTS: Four hundred thirty-nine members of the Missouri Academy of Family Physicians. MEASUREMENTS: Using a mailed questionnaire, physicians were asked for a decision about feeding tube placement in an 89-year-old man who was unable to swallow or communicate after a stroke. Changing the conditions of the scenario, we then evaluated the influence of patient age, duration of disability, a living will, the Cruzan decision, and family preferences on the physician's decision. RESULTS: After reading the initial case history, 47% of physicians opposed tube feedings. Physicians who were told that the patient signed a living will specifically excluding tube feedings were more likely to oppose tube feedings than those who were told that he signed only a standard living will (53% vs 42%; P = 0.02). Forty-two percent of physicians who initially suggested a feeding tube changed their recommendation if the family opposed it. Sixty-six percent of physicians who initially opposed a feeding tube changed their recommendation if the family "pushed" for it. Thirty three percent of physicians who initially opposed tube feedings under the living will scenario would favor tube feedings if the patient had not signed a living will. Twenty-two percent of physicians who initially opposed tube feedings would change to favor them if the issue had arisen before the Cruzan decision. CONCLUSIONS: Among this group of physicians, there was no consensus on whether tube feedings should be initiated. However, it was found that the family's opinion was the most influential factor affecting the physician's recommendation about tube feedings. Most physicians endorsed family preferences for tube feedings even when this intervention was specifically opposed in the patient's living will. PMID- 1634700 TI - A clinicopathological study of CT scans in Alzheimer's disease. AB - OBJECTIVE: To investigate the accuracy of cranial computerized tomography (CT) scans in distinguishing patients with Alzheimer's disease from those with other dementing conditions. DESIGN: Retrospective clinicopathological correlation with pre-mortem CT scans. SETTING: Urban and rural hospitals and nursing homes in the Upper Midwest. PATIENTS: All 507 patients had clinical dementia diagnosed as Alzheimer's disease during life and the subsequent referral of their brains to a dementia brain bank. Of these, 375 patients had had CT scans as part of the diagnostic work-up for dementia. MAIN OUTCOME MEASURES: The presence of neuropathological evidence of Alzheimer's disease and the specific findings on CT scans. RESULTS: Of the 375 patients evaluated with a CT, 28% were misdiagnosed (lacked neuropathological evidence of Alzheimer's disease); of the 132 patients evaluated without a CT scan, only 18% were misdiagnosed (P less than 0.05). The degree of atrophy and other CT findings were similar in the correctly diagnosed and misdiagnosed groups except for increased ventricular size in the correctly diagnosed patients (P less than 0.05). CONCLUSION: Although CT scans do not usually contribute to the recognition of Alzheimer's disease, the presence of ventricular enlargement may help distinguish Alzheimer's disease from other dementias. PMID- 1634701 TI - Sensitivity and specificity of death certificate diagnoses for dementing illnesses, 1988-1990. AB - OBJECTIVE: To evaluate the extent to which mortality data, which is often used to track secular trends for specific diseases, underestimates the prevalence of dementia. DESIGN: Retrospective analysis of existing data. SETTING: Department of Mental Health inpatient facilities in South Carolina. SUBJECTS: Inpatients at Department of Mental Health facilities who were listed in the South Carolina Statewide Alzheimer's Disease and Related Disorders Registry and who died between 1988 and 1990 (n = 450). MAIN OUTCOME MEASURES: Sensitivity and specificity of dementia diagnoses on death certificates compared to medical record diagnoses for inpatients with a pre-mortem dementia diagnosis. RESULTS: Twenty-three percent of death certificates contained any dementia diagnosis (104/450). The sensitivity of death certificates varied by type of dementia (28 percent for Alzheimer's disease; 8 percent for multi-infarct dementia) as well as by race, sex, and age. CONCLUSIONS: Mortality statistics substantially underestimate the prevalence of dementing illnesses and do not fully represent the public health burden of dementia. PMID- 1634702 TI - The use of targeting criteria in hospitalized HMO patients: results from the demonstration phase of the Hospitalized Older Persons Evaluation (HOPE) Study. AB - OBJECTIVE: To determine the yield of standardized targeting criteria for identifying hospitalized HMO patients who are at high risk for mortality and nursing home placement and, therefore, may be appropriate for comprehensive geriatric assessment. DESIGN: Prospective cohort study. SETTING: Four HMO (Southern California Kaiser-Permanente) hospitals. SUBJECTS: 3,697 patients 65 years of age or older admitted to any inpatient service from July 1 through September 30, 1990. MAIN OUTCOME MEASURES: Screening measures for standardized targeting criteria, administered 24-48 hours after admission. RESULTS: Overall, 35.1% of patients screened met at least one inclusionary criterion, which is considerably higher than other published reports. The most commonly met criteria were incontinence, impairment in performing activities of daily living, malnutrition, and immobility. The percentage of patients meeting at least one criterion and meeting each criterion varied considerably among hospitals. The vast majority of patients (83%) who were judged appropriate for assessment met at least three criteria. CONCLUSIONS: The yield of standardized criteria differs when applied to patients in different health care systems and to patients at different hospitals within a health care system, which may reflect differences in the populations being served and the practice styles of physicians and the delivery system. Because no single criterion identified more than approximately half of patients who were judged appropriate for assessment, it is likely that a battery of criteria will be necessary to identify these patients. PMID- 1634703 TI - Anemia and hemoglobin levels in older persons: relationship with age, gender, and health status. AB - OBJECTIVE: To determine the relationship of hemoglobin levels and anemia with age and health status in older adults. DESIGN: Survey. SETTING: Community. PARTICIPANTS AND METHODS: Hematologic tests were obtained from 3,946 adults aged greater than or equal to 71 years in three communities (East Boston, MA; Iowa and Washington counties, IA; and New Haven, CT). RESULTS: Hemoglobin level was inversely associated with age, although this was more pronounced in men than in women. The proportion anemic was equal for men and women aged 71-74 years (8.6%) and increased differentially with age, reaching 41% and 21% for men and women aged greater than or equal to 90 years, respectively. Hemoglobin and anemia were independently associated with age, race, body-mass index, smoking, cancer, hospitalization, renal insufficiency, and hypoalbuminemia. The adjusted relative odds of anemia for a 5-year increase in age was 1.5 (95% confidence interval [CI] 1.3-1.8) for men and 1.2 (95% CI 1.1-1.4) for women. CONCLUSIONS: Age is significantly associated with both hemoglobin levels and anemia, with a stronger effect in men compared with women, even after simultaneously adjusting for demographic characteristics and health status. The decline of hemoglobin and concomitant increased anemia with age is not necessarily a result of "normal aging" so the detection of anemia in an older person should prompt appropriate clinical attention. PMID- 1634704 TI - Glucose tolerance in women: the effects of age, body composition, and sex hormones. AB - OBJECTIVE: To determine the separate and interactive effects of age, phase of the menstrual cycle, menopausal hormone status, body fat mass, and regional fat distribution on glucose tolerance in healthy women. DESIGN: Retrospective study. SETTING: The Baltimore Longitudinal Study of Aging. PATIENTS: Two hundred sixty healthy women aged 22-89 years. MEASUREMENTS: Plasma levels of estradiol and progesterone, body mass index (BMI), waist-to-hip ratio (WHR), and plasma glucose values in the fasting state (FPG) as well as 120 minutes after 40 gm/m2 of oral glucose (G120) were measured for each participant. RESULTS: We found a progressive decline in oral glucose tolerance of 0.4 mM (6.7 mg/dL)/decade at G120) in women from early to late adult years, with no relationship to phase of the menstrual cycle and no abrupt change associated with the menopause. Multiple regression analysis revealed significant, independent effects of BMI and WHR on FPG and G120. The influence of age (P less than 0.01) on G120 was stronger than that of the BMI or WHR (P less than 0.05). There was no significant relationship between the levels of endogenous sex hormones and glucose tolerance after adjustments for age, BMI, and WHR. However, women taking oral contraceptives, but not those receiving postmenopausal replacement therapy, did exhibit mildly elevated G120 values. CONCLUSIONS: Age per se, and to a lesser extent BMI and WHR, but not levels of endogenous sex steroids, contribute to the physiological decline in glucose tolerance in older women. PMID- 1634705 TI - Milacemide: a placebo-controlled study in senile dementia of the Alzheimer type. AB - OBJECTIVE: Milacemide, a MAO-B inhibitor that is also a prodrug for glycine, was tested as a treatment for senile dementia of the Alzheimer type (SDAT) because of its potential for enhancing cognition in animal models of impaired learning and memory. DESIGN: Double-blind, placebo-controlled, randomized clinical trial. SETTING: Sixteen study sites, both university-affiliated and private. PATIENTS: A total of 228 outpatients (116 men and 112 women) with SDAT, ranging in age from 49-93 years. INTERVENTION: 1200 mg/day milacemide treatment for 1 month (113 patients received milacemide, and 115 patients received placebo). MAIN OUTCOME MEASURES: Alzheimer's Disease Assessment Scale and the Mini-Mental State Examination. RESULTS: Milacemide-treated SDAT patients did not show significant improvement in any of the outcome measures used. Significant elevations in liver enzymes in four subjects were of sufficient magnitude to necessitate withdrawal from the study. CONCLUSIONS: Milacemide does not appear to be an effective treatment in enhancing cognition in SDAT patients. PMID- 1634706 TI - Complete heart block presenting as intermittent delirium: case report and review of the literature on cardiac disease in the elderly. PMID- 1634707 TI - Alternative management of cutaneous squamous cell carcinoma in an elderly man: report of a case and review of the literature. PMID- 1634708 TI - Tetanus-diphtheria vaccinations in a veterans nursing home. PMID- 1634709 TI - Progress in gerontology: polymyalgia rheumatica and temporal arteritis. PMID- 1634710 TI - Multidimensional risk assessment versus age as criterion for retirement of airline pilots. AB - OBJECTIVE: To determine whether airline pilots over the age of 60 pose a hazard to aviation safety and whether risk assessment could replace age-based retirement. DATA SOURCES: A computer-assisted literature search (MEDLINE), expert consultation, and government reports. STUDY SELECTION: Original studies on flight performance and pilot age; sudden incapacitation, neuropsychological testing, and/or medication use in pilots; and/or non-invasive testing for predicting sudden death or stroke in asymptomatic subjects. DATA EXTRACTION: Pertinent results and methods data were abstracted from the 49 included studies. DATA SYNTHESIS: No study on aircraft accidents or pilot performance has shown an increased accident risk for over-60-year-old pilots. Normal age-related cognitive changes probably have minimal impact on aviation safety up to age 70, given above average health, education, and experience in airline pilots. Cognitive tests have not been validated for predicting flight performance safety, but they can detect early stages of cognitive disease. Cardiovascular incapacitation risk increases with age, but risk factor profiles and non-invasive tests could identify pilots with non-acceptable risk. CONCLUSIONS: An improved medical certification test could identify those pathologic conditions that might occur more frequently in older subjects. If pilots also underwent adequate performance testing, a gradual increase of the retirement age to approximately age 70 would seem justified. In the future, a longitudinal database should be established to validate medical tests for their ability to predict a pilot's accident risk. Using individual pilots as their own controls might be more sensitive than using population-based norm values. Progress in this field would advance medical assessment for other groups such as air traffic controllers or automobile drivers. PMID- 1634711 TI - The family's will or the living will: patient self-determination in doubt. PMID- 1634712 TI - Gobbledygook geriatrica. PMID- 1634713 TI - Health style. PMID- 1634715 TI - Tracking dementia by the IMC and the MMSE. PMID- 1634714 TI - Low weight and nutritional deficiency. PMID- 1634716 TI - Isolated systolic hypertension. PMID- 1634717 TI - A prospective study of pressure sore risk among institutionalized elderly. AB - OBJECTIVE: To determine if dietary intake, nutritional status, and other physical markers are risk factors for the development of pressure sores in the elderly. DESIGN: Cohort study. SETTING: 250-bed skilled nursing facility with 90 extended care beds in which the average length of stay is 28 days. PATIENTS: Two hundred newly admitted residents (70% female, 95% Caucasian) who were over age 65, estimated to stay greater than 10 days, at risk for pressure sore development (Braden Scale score less than or equal to 17) but free of existing pressure sores were studied for 12 weeks or until discharge. MEASURES: Skin assessment, Braden Scale score, blood pressure, body temperature, anthropometrics, and dietary intake were studied weekly. CBC, serum albumin, serum total protein, serum iron, iron binding capacity, serum zinc and copper, and serum vitamin C were studied weekly for 4 weeks and biweekly for 8 weeks. MAIN OUTCOME MEASURES: Presence/absence and stage of pressure sores. MAIN RESULTS: Stage I pressure sores developed in 70 (35%) and Stage 2 or worse in 77 (38.5%) residents. Subjects who developed pressure sores were older (P less than 0.001) and had lower systolic and diastolic blood pressure (P less than 0.001) and higher body temperature (P less than 0.001) than those without pressure sores. Dietary intake of all nutrients was lower among subjects who developed pressure sores. Using logistic regression, the best predictors or pressure sore development were the Braden Scale score, diastolic blood pressure, temperature, dietary protein intake, and age. CONCLUSIONS: Risk assessment is recommended upon admission to a nursing home and weekly for the first month. Risk status can be effectively predicted by using the Braden Scale in combination with knowledge of age, blood pressure, temperature, and dietary protein intake. PMID- 1634718 TI - Post-operative delirium: predictors and prognosis in elderly orthopedic patients. AB - OBJECTIVE: To compare the effect of post-operative analgesia using epidural versus intravenous infusions on the incidence of delirium after bilateral knee replacement surgery in elderly patients. Additional risk factors and impact on post-operative recovery were also assessed. DESIGN: Prospective randomized controlled trial. SETTING: Urban referral hospital specializing in elective orthopedic surgery. PATIENTS: 60 consecutive patients undergoing bilateral knee replacement surgery with epidural anesthesia were approached; 51 patients were eligible and consented. The mean age was 68, 55% were women, and there was a high prevalence of comorbid medical disease. No patient was demented pre-operatively. INTERVENTION: Random allocation to either continuous epidural infusion of bupivacaine and fentanyl or continuous intravenous infusion of fentanyl. Infusions were initiated at the first complaint of pain and continued through the 36- to 48-hour stay in the recovery room. MAIN OUTCOME MEASURE: Acute post operative delirium defined using an algorithm based on DSM III criteria. RESULTS: The overall incidence of acute delirium was 41%, with no difference between types of post-operative analgesia. Predictors of delirium were age, gender, and pre operative alcohol use. All cases resolved within 1 week, and length of stay and achievement of physical therapy goals were the same for delirious and non delirious patients. CONCLUSIONS: There is a high incidence of post-operative delirium in elderly non-demented patients following bilateral knee replacement, regardless of whether post-operative analgesia is administered by the epidural or intravenous route. PMID- 1634719 TI - Delusions and behavioral disturbances in cognitively impaired elderly persons. AB - OBJECTIVE: To compare cognitive function and the prevalence of selected behavioral problems in delusional and non-delusional dementia patients. DESIGN: Retrospective medical record review. SETTING: An outpatient geriatric assessment center. PARTICIPANTS: 114 consecutive patients with dementia. MAIN OUTCOME MEASURES: Delusions as recorded in a consultation report. RESULTS: Delusions were described in 25.5% of patients. A variety of behavioral disturbances were more common in delusional than non-delusional patients, including agitation, angry or hostile outbursts, urinary incontinence, wandering or pacing, and insomnia. While cognitive function as measured by the MMSE was similar in delusional and non delusional patients (18.9 +/- 3.8 and 19.2 +/- 5.9, respectively), there was a statistically borderline tendency for delusions to occur more often in patients in the mid-range of cognitive impairment (17 less than or equal to MMSE less than or equal to 23) compared with patients with greater or lesser degrees of cognitive impairment (32% vs 17% respectively). CONCLUSION: Delusions in dementia are associated with a variety of behavioral problems. Further studies are needed to clarify the role of delusions in the development of disruptive behaviors in dementing illness. PMID- 1634720 TI - The risk factors of age and family history and their relationship to screening mammography utilization. AB - OBJECTIVE: To study the association of two well known risk factors for breast cancer and the association of knowledge of those risk factors with mammography utilization. DESIGN: Cross sectional: two independent random telephone surveys. SETTING: Two Northeastern metropolitan communities surveyed in 1987 and in 1989. PARTICIPANTS: Women without breast cancer who spoke English and who were between 45 and 75 years of age. MAIN OUTCOME MEASURES: The two risk factors measured were a family history of breast cancer and being 65 or older. Participants were surveyed about their knowledge of risk factors, presence of risk factors, selected beliefs, attitudes, reinforcing factors and mammography use. Results were analyzed for women 50-75. RESULTS: There was a substantial increase in mammography use over the 2-year period. Having a positive family history or being older is not associated with increased mammography utilization. Knowledge that family history and/or age are risks is associated with increased utilization. However, knowledge of risk factors is not associated with having those risks. Older women have lower utilization than younger women regardless of their knowledge of age as a risk. Increased physician recommendation is associated with increased utilization. CONCLUSION: Since knowing that a factor is a risk and having a physician recommend mammography are each associated with increased use, we conclude that the primary care physicians' role in increasing mammography utilization is critical. PMID- 1634721 TI - Napping and 24-hour sleep/wake patterns in healthy elderly and young adults. AB - OBJECTIVE: To examine differences between healthy elderly and young adults in daytime napping, nocturnal sleep, and 24-hour sleep/wake patterns. A second objective was to determine whether elderly subjects with more and less frequent naps differed in their clinical features or nocturnal sleep. DESIGN: Survey by sleep/wake logs and polysomnography. Comparison by age. SETTING: Sleep/wake logs were completed in the subjects' homes. Polysomnographic studies were conducted on an outpatient basis in a sleep and chronobiology research laboratory. SUBJECTS: Convenience samples of forty-five healthy subjects over 78 years of age (21M, 24F) and 33 healthy adults between 20 and 30 years of age (20M, 13F). MAIN OUTCOME MEASURES: Using self-reports, we estimated the frequency and timing of daytime naps; timing, duration, and quality of nocturnal sleep; and 24-hour patterns of sleep and wakefulness. Also polysomnographic sleep measures. RESULTS: Compared to young adults, elderly subjects reported a greater mean number of daytime naps (P = .004), shorter nocturnal sleep with more wakefulness and earlier sleep hours (P less than .003 for each), and a trend for a shorter 24 hour sleep fraction. Among the elderly, more-frequent and less-frequent nappers did not differ in clinical ratings, self-report sleep measures, or polysomnographic measures. There was a trend for more sleep-disordered breathing and periodic limb movements in more frequent nappers. CONCLUSIONS: These findings are consistent with an age-related decrease in amplitude of the circadian sleep propensity rhythm, or with the expression of a semi-circadian (12-hour) sleepiness rhythm. However, we cannot exclude the additional possibility that napping results from lifestyle factors and nocturnal sleep pathologies in a subset of the elderly. PMID- 1634722 TI - Hypnotics, sleep, and mortality in elderly people. AB - OBJECTIVE: To re-assess relationships between mortality, hypnotic use, subjective insomnia, and sleep duration. DESIGN: A prospective study examining 5-year mortality among hypnotic drug users and respondents with subjective insomnia identified in a longitudinal study of health, activity, and lifestyle (Nottingham Longitudinal Study of Activity and Ageing). SETTING: General community. PARTICIPANTS: 1042 survey respondents, aged over 65 years, randomly selected from the community and stratified at age 75 years. MAIN OUTCOME MEASURE: Recorded mortality. RESULTS: During the 5-year period, 352 respondents died. The mortality rate was significantly greater among those taking some form of medication for sleep (n = 208) than for those not taking sleep medication (n = 812; chi-square = 4.91, df = 1, P = 0.027). When sleep medication users were categorized as either "hypnotic users" (ie, users of medication with recognized hypnotic or sedative actions) or "other users" (including analgesics and other over-the-counter medicines), only "other users" showed significant excess mortality (chi-square = 7.27, df = 1, P = 0.007). Logistic regression showed that "other users" were 2.5 times more likely to die than "non-users" even when gender, health risk, and usual sleep duration were controlled. There were no significant relationships between mortality and subjective insomnia or reported duration of sleep. CONCLUSIONS: Earlier reported relationships between excess mortality and use of medication for sleep are replicated in this study. Among elderly people, however, this relationship does not derive from the pharmacological characteristics of prescription hypnotics. Rather, it appears that reported self-medication to promote sleep, using a variety of non-sedative products, provides an epidemiological "marker" for a group within which levels of morbidity and mortality are particularly high. Excess mortality associated with very short or long sleep duration was not replicated in this study. Overall, these findings provide little epidemiological support for a wide-spread interaction between benzodiazepine hypnotic use and sleep disordered breathing in old age. PMID- 1634723 TI - Risk factors for early hospital readmission in a select population of geriatric rehabilitation patients: the significance of nutritional status. AB - OBJECTIVE: To test the strength of the evidence in favor of the hypothesis that protein-energy undernutrition is an independent risk factor for non-elective hospital readmission within 3 months of discharge in a population of elderly hospitalized patients. DESIGN: Retrospective analysis of data from prospective observational study. METHODS: All 110 elderly patients admitted to a geriatric recuperative care and rehabilitation unit during a 6-month period completed a comprehensive in-patient evaluation. Ninety-eight of these patients were subsequently discharged alive and followed prospectively for 3 months. All hospital readmissions during the observation period were identified by patient interview and, within the VA hospital system, computer tracking of admissions. Based on the discharge assessment, the strongest predictors of non-elective readmission were identified using univariate and multivariate statistical procedures. RESULTS: Twenty-eight of the 98 patients discharged alive and completing the 3-month follow-up (29%) had at least one non-elective readmission. The patients discharged home were non-electively readmitted more frequently than were the patients discharged to a nursing home (32% vs 11%, P = 0.05). Of the 109 discharge assessment variables analyzed, the best predictor of which patients would have at least one non-elective hospital readmission was the discharge serum albumin, followed by a diagnosis of dementia, discharge gamma globulin, the subscapular skinfold thickness, home ownership, and the discharge Katz Index of ADL score. Discharge serum albumin concentration, subscapular skinfold thickness, and discharge serum gamma globulin concentration were all negatively correlated with risk of non-elective readmission. The presence of functional debilitation or dementia was associated with a lower likelihood of non-elective readmission compared with the absence of these conditions. CONCLUSIONS: Protein-energy undernutrition appears to be a strong independent risk factor for non-elective hospital readmission especially among the highest risk patients, those who are functionally independent and cognitively intact. PMID- 1634724 TI - The relations among caregiver stress, "sundowning" symptoms, and cognitive decline in Alzheimer's disease. AB - OBJECTIVE: To investigate the relations among the initial perceived stress of Alzheimer patients' caregivers, the rate of change of perceived stress, patients' sundowning behaviors, and patients' rate of cognitive decline. DESIGN: A longitudinal cohort study in which Alzheimer patients and their caregivers were assessed at 6-month intervals. SETTING: Hospital out-patient clinic. Patients and caregivers lived at home. SUBJECTS: Subjects were 35 patients (50-79 years) with Alzheimer's disease and their primary caregivers (24 males and 11 females); all caregivers were spouses. METHODS: At time of entry into the study, caregivers indicated which of seven behaviors indicative of sundowning were exhibited by the patient. Patients were evaluated successively using the Mini-Mental State Examination, whereas caregivers completed the Perceived Stress Scale, provided an index of social support utilization, and completed the Beck Depression Inventory. MAIN OUTCOME MEASURES: Caregivers' initial perceived stress and the rate of change of perceived stress, patients' sundowning behavior, and rate of cognitive decline. RESULTS: The pattern of correlations indicated that both rate of cognitive decline and initial sundowning behavior were significantly correlated with initial perceived caregiver stress. The average rate of increase of caregivers' perceived stress was positively correlated with the initial incidence of sundowning behaviors, even when controlling for the effects of caregiver depression and social support utilization. CONCLUSION: Sundowning behavior of Alzheimer patients is associated with an increased rate of change of caregivers' perceived stress. This association may be specific to sundowning behavior because there was no relation between the rate of change of perceived stress and morning agitation. The findings suggest that future caregiver intervention programs could profitably focus on sundowning behavior rather than general agitation. PMID- 1634725 TI - Urinary tract infections and estrogen use in older women. AB - OBJECTIVE: To examine the relationship between exogenous estrogen use and risk of clinically diagnosed urinary tract infection (UTI) in older women. DESIGN: A case control study. SETTING: Two hundred seventy-six general practices. PATIENTS: Cases (n = 3,616) were women, age 50-69 years, with a first recorded UTI in the calendar years 1989 or 1990. Controls (n = 19,162) were matched for age and practice. MAIN OUTCOME MEASURE: Clinical diagnosis of UTI. RESULTS: Women using estrogens for greater than or equal to 1 year had an increased risk of being diagnosed with a UTI compared to non-users, crude odds ratio (OR) 1.9 (95% CI 1.5 2.2). All of this excess risk was observed in women with intact uteri, OR 2.1 (CI 1.7-2.7). Hysterectomized women had no increased risk, OR 1.1 (CI 0.8-1.5). Controlling for diabetes, neurologic deficit, atrophic vaginitis, incontinence, and age did not affect the observed associations. CONCLUSION: Estrogen use is associated with an increased risk of UTI in older women with intact uteri but not in hysterectomized women. This observed differential effect on women with or without uteri may be explained by prescribing biases between these two groups of women, but we lack any evidence to support this conclusion over several alternative possibilities. PMID- 1634726 TI - Group A streptococcal bacteremia associated with gastrostomy feeding tube infections in a long-term care facility. PMID- 1634727 TI - Classic hemophilia in elderly patients. PMID- 1634728 TI - The "fractured Foley": an unusual complication of chronic indwelling urinary catheterization. PMID- 1634729 TI - Delirium in older patients. PMID- 1634730 TI - (-)Deprenyl-medication: a strategy to modulate the age-related decline of the striatal dopaminergic system. AB - (-)Deprenyl (Selegiline, Jumex, Eldepryl, Movergan), a close structural relative to phenylethylamine (PEA), is a drug with a unique pharmacological spectrum. (1) It is a highly potent and selective, irreversible inhibitor of B-type monoamine oxidase (MAO), a predominantly glial enzyme in the brain. The activity of this enzyme significantly increases with age. (-)Deprenyl, the first selective inhibitor of MAO-B described in literature, has become the universally used research tool for selectively blocking B-type MAO. It is the only MAO-B inhibitor in clinical use. (2) (-)Deprenyl interferes with the uptake of catecholamines and indirectly acting sympathomimetics because it is handled by the catecholaminergic neuron in a way similar to the physiological substances transported through the axonal end organ and vesicular membrane. The unique behavior of (-)deprenyl is that, in striking contrast to PEA and its relatives, it does not displace the transmitter from storage, ie, it is not a releaser. The net result is that ( )deprenyl inhibits the releasing effect of tyramine, and, at present, is the only safe MAO inhibitor that can be administered without dietary precautions. (3) Maintenance on (-)deprenyl selectively enhances superoxide dismutase (SOD) and catalase activity in the striatum. This effect is unrelated to its effect on MAO B and the inhibitory effects of the drug on neurotransmitter uptake. (4) Maintenance on (-)deprenyl facilitates the activity of the nigrostriatal dopaminergic neurons with remarkable selectivity, and this effect, too, is unrelated to either its effects on MAO or on neurotransmitter uptake. (5) Maintenance on (-)deprenyl prevents the characteristic age-related morphological changes in the neuromelanin granules of the neurocytes in the substantia nigra. All in all, (-)deprenyl increases the activity of the nigrostriatal dopaminergic system and slows its age-related decline. Maintenance of male rats on (-)deprenyl delays the loss of the capacity to ejaculate, slows the decline of learning and memory, and significantly lengthens the life-span as compared with saline-treated rats. Parkinson's disease patients on levodopa plus (-)deprenyl (10 mg daily) live significantly longer than those on levodopa alone. (-)Deprenyl is the first drug that retards the progress of Parkinson's disease. Newly diagnosed Parkinson's disease patients maintained on (-)deprenyl need levodopa significantly later than their placebo-treated peers. Maintenance on (-)deprenyl improves significantly the performance of patients with Alzheimer's disease. It is concluded that Parkinson's disease and Alzheimer's disease patients need to be treated daily with 10 mg (-)deprenyl from diagnosis until death, irrespective of other medication.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1634732 TI - Advance directives on restraints. PMID- 1634731 TI - Delusions, delirium, and cognitive impairment: the challenge of clinical heterogeneity. PMID- 1634733 TI - At least routine laboratory assessment... PMID- 1634734 TI - Teaching about urinary incontinence. PMID- 1634735 TI - Quality graduates mean power to the profession. PMID- 1634736 TI - Standards of care. PMID- 1634737 TI - Premises liability. PMID- 1634738 TI - The unification of European optometry. PMID- 1634739 TI - Evaluating the laws defining blindness. AB - The law defining legal blindness was written in 1935, and has not been updated since. A historical view of the background in the development of this law and a comparison to laws used in other countries helps to point out some problems with the current definition. As the population gets older, the prevalence of visual impairment will be increasing. To administer programs, distribute funding, and ensure adequate care, the problems inherent in the definition of legal blindness must be addressed, and the law must be revised. PMID- 1634740 TI - Vascular implications of optic atrophy. AB - Optic atrophy can often be a result of arterial blood flow insufficiency associated with systemic vascular disease (cardiovascular disease, hypertension, or diabetes mellitus). The lack of adequate blood perfusion pressure can create conditions leading to anoxia and death of the nerve fiber layer with a resultant visual field defect. A case of a 63-year-old white male is presented with optic atrophy resulting from anterior ischemic optic neuropathy 5 years earlier. A review of the literature concerning the more common causes of ocular vascular insufficiency (i.e., anterior ischemic optic neuropathy, internal carotid disease, central retinal artery occlusion, and branch retinal artery occlusion) as well as diagnostic testing and therapeutic management is discussed. PMID- 1634741 TI - Norrie's disease vs. PHPV: one family's dilemma. AB - This paper presents the numerous similarities between Norrie's disease and bilateral persistent hyperplastic primary vitreous. A description of each disease is given, as well as a case report which demonstrates the difficulty in distinguishing the two disease processes when there is a negative family history of blindness. A discussion section focuses on the need for a better differential protocol for Norrie's disease, which would aid the clinician when a family history of blindness is absent. PMID- 1634742 TI - Duane's retraction syndrome. AB - The clinical findings for 29 patients with Duane's retraction syndrome (DRS) are reported. Similar to other studies, a preponderance of females, left eye involvement, and type I DRS occurred. The incidence of both anisometropia and amblyopia was somewhat higher than for the normal population. Unexpectedly, complaints of diplopia existed for seven patients. PMID- 1634743 TI - Retention of patient records. AB - Patient records are essential to provide patients with appropriate health care and to preserve patients' rights. Patient records are also vital to help practitioners defend lawsuits. Therefore, practitioners must maintain patient records in good order for as long as possible. This paper discusses the clinical and legal issues involved in record retention, including the relevant state regulations and record requirements in other health care fields, to provide guidelines for retention of optometric patient records. Based on the statutes of limitations, common practice and sound medical and legal advice, optometric patient records should be retained for a minimum of 10 years after the patient was last seen. Ideally, patient records should be retained forever. PMID- 1634744 TI - Peer review of expert medical-legal testimony: a proposal for child neurology. PMID- 1634745 TI - Medulloblastoma: II. A pathobiologic overview. AB - The pathobiology of medulloblastoma is reviewed in light of emerging data regarding its immunocytochemical and cytobiologic, as well as molecular biologic, characteristics. The nature of the lesion, particularly its nosologic relation to primitive neuroectodermal tumor, is discussed, as is its place in the World Health Organization classification of tumors of the central nervous system. PMID- 1634746 TI - Nervous system dysfunction in children with paraneoplastic syndromes. AB - Paraneoplastic syndromes are complexes of symptoms and signs that occur in association with cancer and that are unexplained by the known anatomic and physiologic characteristics of the tumor. Many of these syndromes are neurologic in nature or have consequences for the central or peripheral nervous system. These syndromes have been well characterized in adults. With the exception of opsoclonus-myoclonus, little has been written about the occurrence of such syndromes in children. This review looks at published reports of paraneoplastic syndromes in children and concludes that paraneoplastic syndromes in childhood differ from those seen in adulthood because of differences in both the host and the kinds of neoplasms most prevalent in each age group. Paraneoplastic syndromes may be underreported in childhood because of the difficulty in eliciting specific neurologic complaints from children and because a thorough neurologic examination is often not undertaken as a matter of routine. PMID- 1634747 TI - Spontaneous intracerebral hemorrhage: a very late delayed effect of radiation therapy. AB - Cerebral necrosis is a well-known delayed sequela of radiation to the central nervous system. Delayed intracerebral hemorrhage occurring several years after radiation is rare; however, with increased survival, this complication will become more common. We report a child who developed a brain-stem hemorrhage 4.5 years following radiation therapy for brainstem tumor. The possible pathogenesis for the spontaneous hemorrhage is discussed. The onset of the neurologic symptoms in this setting occurs later than the usual symptoms of radiation necrosis. It is important to recognize this entity as a late delayed complication of radiation therapy and not to mistake it for tumor recurrence. PMID- 1634748 TI - Follow-up study of muscle function in children of mothers with myasthenia gravis during pregnancy. AB - Most infants whose mothers have myasthenia gravis are healthy at birth, but 10% to 15% have a transient neonatal form of myasthenia gravis. In this study, the muscular function and neuromuscular transmission were examined in 31 children, aged 3 months to 31 years (median, 10 years), of 15 myasthenic mothers. Eleven of these children had had the neonatal form of myasthenia gravis. The children were examined clinically and with neurophysiologic methods. Blood samples were taken for HLA typing, creatine kinase levels, and myoglobin and acetylcholine receptor antibody studies. Twenty-nine of the 31 children had no signs of neuromuscular disease. Two children (who had had neonatal myasthenia gravis) had a moderate stationary myopathy, probably unrelated to the myasthenia gravis of their mother. Creatine kinase levels were normal for all subjects. Acetylcholine receptor antibody levels were similar to those of a control population. The HLA type B8 antigen was not significantly more prevalent in the children who had had neonatal myasthenia gravis than in the healthy children. Neonatal myasthenia gravis in a previous sibling was the only factor in the material that predicted the occurrence of myasthenic symptoms in the neonatal period. PMID- 1634749 TI - Cartoons of famous neurologists by Milt Gross. PMID- 1634750 TI - Angelman syndrome: clinical profile. AB - To further delineate the clinical and developmental features of Angelman syndrome, we collected data through three sources of information: (1) physical examinations; (2) laboratory data and family questionnaire data of affected individuals; and (3) literature review. The questionnaire data describes a generally normal prenatal and birth history. Feeding difficulties, developmental delay, or seizures were the presenting problems in all infants. The diagnosis of Angelman syndrome, however, was not made in any infant prior to 1 year of age. Except for seizures, no medical or surgical complication was common, although a variety of visual complaints or findings were common. Sixty percent of Angelman syndrome children had a cytogenetically demonstrated deletion of chromosome 15q11 q13. The individuals with and without a deletion could not be differentiated clinically. Diagnosis in early childhood is therefore difficult, and a high index of suspicion is recommended. PMID- 1634751 TI - Improved neuropsychological outcome in children with brain tumors diagnosed during infancy and treated without cranial irradiation. AB - Neuropsychological outcome of 28 patients with brain tumors diagnosed before the age of 36 months (mean, 19 months) was assessed using a comprehensive battery of tests. Elapsed time between diagnosis and testing averaged 6.2 years. Half the patients had received cranial radiation therapy and surgery, with and without chemotherapy, whereas the rest had received only surgery, with or without chemotherapy. Groups were comparable with respect to tumor diagnosis and location, age at diagnosis, race, and sex. Intellectual functioning was significantly lower in children whose treatment included cranial irradiation than in those treated without cranial irradiation, and this effect was more pronounced in nonverbal than in verbal intellectual abilities. Mean scores for the radiation group were lower than for the no-radiation group in all areas assessed and were significantly below age-based normative means in five of the eight cognitive areas: intellectual, memory, attention, motor, and visual-spatial skills. Mean scores for children in the no-radiation group were generally within the average range in all cognitive areas except visual-spatial skills, which were significantly below age-based normative means. Endocrine deficiencies and growth retardation were much more prevalent in patients treated with cranial irradiation. Because the immature brain is susceptible to treatment-related pathologic changes, infants are at greater risk than older children for significant, long-term neuropsychological, endocrine, and growth sequelae. In children treated without cranial irradiation, morbidity was minimized without an increased rate of mortality. PMID- 1634752 TI - Cerebral tumors in children presenting with epilepsy. AB - The records of 20 children with seizures who had cerebral tumor confirmed histologically between 1979 and 1989 have been reviewed. These patients represented 2.9% of all children presenting with seizures. Forty percent were aged 15 months or younger, all of whom presented with partial seizures. Initial misdiagnosis of seizures occurred in 25% of these infants. Examination was normal in 75% of the study group. Behavior disturbance was present in 50%, with deterioration occurring in 60% of these. Electroencephalograms revealed focal abnormalities in 62% and generalized abnormalities in 25% when performed. Cranial ultrasound was performed in two cases, with false-negative results. Computed tomographic scan findings were not diagnostic of tumor in 40%. Magnetic resonance imaging confirmed the presence of tumor in all children in whom it was performed. Tumors most frequently involved the temporal lobes (55%) and the frontal lobes (40%). Surgical intervention resulted in considerable improvement in seizure control in 75%. Surgery is useful in the control of tumor-related seizures and should be considered early in the treatment of this disorder. Suspicion of tumor should increase when seizures are partial or refractory, particularly if intelligence and physical examination are normal or if there is progressive deterioration in behavior. The most appropriate type of brain imaging is magnetic resonance imaging scan. PMID- 1634753 TI - Etiology of lateral rectus palsy in infancy and childhood. AB - The etiologies of lateral rectus palsy in 132 infants and children seen over a period of 22 years in a university medical center were retrospectively reviewed and compared with similar reports in the literature. Unlike most reports, which lump children with adults, this study focuses on childhood etiologies of lateral rectus palsy. In contrast to the only two studies in the literature on childhood lateral rectus palsy, which reflect a purely ophthalmologic perspective, this study reflects experiences of pediatric neurology and pediatric neurosurgery, as well as ophthalmology. Most lateral rectus palsies were unilateral, almost equally distributed between right and left sides. Trauma, tumor, and congenital etiologies were the most prevalent. The relative frequency of each of these etiologies varies by service (neurology, neurosurgery, ophthalmology). In 10.6% of patients, etiology could not be determined. The majority of patients had an isolated lateral rectus palsy. Association of lateral rectus palsy with other cranial nerve palsies and/or long tract signs characterized trauma and tumor. The majority of tumors were primary and infratentorial. A small number of patients had benign recurrent lateral rectus palsy. PMID- 1634754 TI - Trichothiodystrophy: report of a new case with severe nervous system impairment. PMID- 1634755 TI - Plantar responses in infants. PMID- 1634756 TI - The future of child neurology. PMID- 1634757 TI - The matter of madness: perspectives on the history of psychiatry. PMID- 1634758 TI - Myelosuppressive effects in vivo of purified recombinant murine macrophage inflammatory protein-1 alpha. AB - Purified recombinant murine macrophage inflammatory protein-1 alpha (rmuMIP-1 alpha), a cytokine with myelopoietic activity in vitro, was assessed in vivo by injection into C3H/HeJ mice for effects on proliferation (percentage of cells in S phase DNA synthesis of the cell cycle) and absolute numbers of granulocyte macrophage, erythroid, and multipotential progenitor cells in the femur and spleen, and on nucleated cellularity in the bone marrow, spleen, and blood. rmuMIP-1 alpha rapidly decreased cycling rates (at 2 to 10 micrograms/mouse i.v.) and absolute numbers (at 5 to 10 micrograms/mouse i.v.) of myeloid progenitor cells in the marrow and spleen. These effects were dose- and time-dependent and reversible. Suppressive effects were noted within 3 to 24 h for cell cycling and absolute numbers of progenitor cells in the marrow and spleen, and by 48 h for circulating neutrophils. A study comparing the effects of i.v. injection of rmuMIP-1 alpha versus rmuMIP-1 beta, a biochemically similar molecule but with no myelosuppressive effects in vitro, demonstrated myelosuppression in vivo by rmuMIP-1 alpha, but not by rmuMIP-1 beta. The results suggest that rmuMIP-1 alpha has myelosuppressive activity in vivo and offers the possibility that it may be a useful adjunct to treatments involving cytotoxic drugs because of its reversible suppressive effects on normal progenitor cell cycling. PMID- 1634759 TI - An immunosuppressive retrovirus-derived hexapeptide interferes with intracellular signaling in monocytes and granulocytes through N-formylpeptide receptors. AB - We have previously found that the retroviral p15E-derived hexapeptide LDLLFL is a potent inhibitor of the FMLP-induced polarization response that is an early event in chemotaxis of monocytes and granulocytes. We investigated the mechanism of action of LDLLFL. LDLLFL inhibited the changes in [Ca2+]i in response to FMLP, but not to C5a or leukotriene B4. The reverse peptide LFLLDL was not inhibitory. In the presence of LDLLFL, the FMLP dose-response curve shifted to higher concentrations, indicating that LDLLFL interfered with binding of FMLP to its receptor. Indeed, binding of [3H]FMLP to neutrophilic granulocytes was inhibited in the presence of LDLLFL. Furthermore, immunosuppressive LDLLFL homologs also inhibited binding of FMLP to granulocytes, whereas noninhibitory LDLLFL homologs did not. Our results suggest that retroviral p15E and p15E-like factors, which can be found in serum of patients with cancer or chronic upper airway infections, may interfere with the interaction of N-formylpeptides derived from (opportunistic) bacteria, with monocytes and granulocytes. This receptor interference may impair monocyte and granulocyte reactivity toward these agents. PMID- 1634760 TI - Priming of the respiratory burst of bone marrow-derived macrophages is associated with an increase in protein kinase C content. AB - The biochemical mechanism(s) underlying the priming of the macrophage for an enhanced PMA-induced respiratory burst is not understood. Because the cellular receptor for PMA is thought to be protein kinase C (PKC), we have investigated the effects of priming agents on cellular PKC levels. Sonicates from unprimed bone marrow-derived macrophages (BMM) were found to contain PKC activity (309 +/- 51 pmol 32P-incorporated/mg/min; mean +/- SE, n = 17) as measured by the phospholipid-, diacylglycerol-, and calcium-dependent phosphorylation of histone. Exposure of BMM to priming agents such as TNF-alpha, LPS, and granulocyte/macrophage-CSF resulted in a significant increase in both histone phosphorylating activity and levels of immunoreactive PKC protein in these cells. A minimum of 6-h exposure, with an increasing effect up to 48 h, was required for a detectable increase in PKC level. The activity from primed BMM, like that of the untreated cells, was predominantly cytosolic. The kinetics and concentration dependence of the priming agent-induced increase in the PKC content of BMM closely paralleled the enhancing effects of these agents on the PMA-stimulated respiratory burst. Furthermore, CSF-1, a cytokine that does not prime BMM, failed to increase PKC activity. We propose that the exposure of BMM to priming agents leads to an increase in the expression of a stimulatory isozyme(s) of PKC, resulting in an enhanced ability to mount a respiratory burst in response to stimulation with PMA. PMID- 1634761 TI - Collagen-induced arthritis in rats. Examination of the epitope specificities of circulating and cartilage-bound antibodies produced by outbred and inbred rats using cyanogen bromide-derived peptides purified from heterologous and homologous type II collagens. AB - To determine the number and location of antibody binding epitopes on type II collagen, outbred and inbred rats were immunized with chick, bovine, human, and rat type II collagen (CII, BII, HII, and RII); all sera were assayed for reaction with a panel of CB peptides purified and renatured from the immunizing collagen and from RII. Antibody reaction patterns (profiles) varied among individual outbred rats but were essentially constant over time and changed little after boosting. The strongest antibody reactions were to CB11, CB9-7, and CB12 followed by CB8, CB10, and CB6. Antibody profiles varied depending on the species of collagen used for immunization and the strain of rat immunized. Except for CB10, where antibodies were largely specific for heterologous collagens, antibodies reactive with all other CB peptides cross-reacted strongly with renatured rat CB peptides. Sera from inbred BB rats immunized with BII, CII, or HII reacted best with CB11, unlike antisera to RII that reacted strongly with CB9-7. Inbred LEW, COP, WKY, F344, and BUF rats immunized with BII reacted strongest with CB9-7 and variably with CB11 and CB12. BBxLEW F1 hybrid rats reacted almost equally with CB11 and CB9-7 producing an antibody profile intermediate to those elicited in the parent strains. Finally, antibodies reactive with rat CB11, CB9-7, and CB12 could be eluted from normal rat cartilage incubated in anti-BII serum; antibody eluate profiles generally paralleled the profile produced by the sera applied to cartilage. Taken together, these findings indicate that multiple antibody reactive epitopes on type II collagen may be instrumental in the initiation of collagen-induced arthritis in rats, particularly shared or cross-reactive epitopes located within CB11, CB9-7, CB12, and CB8. PMID- 1634762 TI - Anticardiolipin antibodies in NZW x BXSB F1 mice. A model of antiphospholipid syndrome. AB - NZW x BXSB F1 (W/B F1) male mice develop systemic lupus-like disease, and several autoantibodies, circulating immune complexes, and lupus nephritis become apparent. The abnormally high incidence of degenerative coronary vascular disease with myocardial infarction and thrombocytopenia due to the presence of both platelet-associated antibodies and circulating antiplatelet antibodies in this animal has been reported. We found that W/B F1 male mice produced autoantibodies against cardiolipin (aCL) and that the titer of aCL increases with age. aCL from W/B F1 male mice were mainly IgG and binding activity to cardiolipin was aCL cofactor (beta 2-glycoprotein I (beta 2-GPI)) dependent. We developed monoclonal aCL from these animals and examined specificity of the autoantibodies. All the mAb used reacted with the negatively charged phospholipids, cardiolipin, phosphatidylserine, and phosphatidylinositol, and some reacted with platelets and DNA. The addition of human or mouse beta 2-GPI enhanced the titer for monoclonal aCL from the W/B F1 mice. From the results of competitive inhibition enzyme immunoassay with monoclonal aCL and purified beta 2-GPI, aCL from the W/B F1 mice recognized the complex of CL and beta 2-GPI. The W/B F1 male mouse may be an appropriate model for use in studies on the pathologic significance of aCL in patients with antiphospholipid syndrome. PMID- 1634763 TI - Circumvention of the induction of resistance in murine experimental autoimmune thyroiditis by recombinant IL-1 beta. AB - Murine experimental autoimmune thyroiditis (EAT) is induced in genetically susceptible mice by immunization with mouse thyroglobulin (MTg). We have previously shown that raising the level of circulatory MTg for greater than or equal to 2 to 3 days, by the i.v. injection of soluble MTg or the infusion of thyroid-stimulating hormone, rendered these mice resistant to subsequent EAT induction. The Ag-specific resistance was mediated by CD4+ Ts cells, and the induction of unresponsiveness could be interfered with by injecting the T cell adjuvant poly(A).poly(U) 3 h after MTg pretreatment. To dissect further the cytokine signals involved in circumventing the induction of resistance, the effect of human rIL-1 beta was examined. As with poly(A).poly(U), mice given 4000 or 10,000 U or rIL-1 beta 3 h after deaggregated MTg (dMTg) were not resistant to EAT induced with MTg and adjuvant. Moreover, mice given 90,000 U or rIL-1 beta after dMTg and then immunized displayed very severe thyroiditis, strong in vitro proliferative response, and high antibody titers, compared with immunized controls, indicating a dose-dependent effect of rIL-1 beta. The intermediate dose of 10,000 U or rIL-1 beta was selected to determine the importance of time interval between dMTg and rIL-1 beta administration. Interference with the induction of suppression was more efficacious when rIL-1 beta was given at 3 h than at 24 h, but at 24 h it was no more effective than 4000 U given at this interval. In contrast, mice given 10,000 U of rIL-1 beta 3 h before dMTg and then challenged developed MTg antibodies but little thyroiditis, demonstrating that the interference with suppression of autoantibody responses can occur without altering the induction of suppression of thyroiditis. The injection of rIL-1 beta also led to a sharp but transient rise in serum IL-6. The short t1/2 of IL-6 suggests that any role played by IL-6 would require critical timing. Murine rIL-2 given at 1 and 2 days after dMTg had a minimal effect on induced resistance. Lastly, immunization of dMTg-pretreated mice with MTg and rIL-1 beta did not induce EAT, demonstrating that rIL-1 beta could not interfere with established suppression. Thus, the intervention by rIL-1 beta in MTg-induced suppression occurs at a critical time, early after the injection of dMTg but before the establishment of resistance. PMID- 1634764 TI - Novel human autoantibodies reactive with 5'-terminal trimethylguanosine cap structures of U small nuclear RNA. AB - A class of RNA-containing particles, U small nuclear/nucleolar ribonucleoprotein particles (U snRNP), are well known to be targets for sera from patients with various autoimmune diseases. In the most cases the protein components carry the antigenic determinants. We have identified serum autoantibodies from three patients with systemic sclerosis that were directed against U1-U5 snRNA by immunoprecipitation of deproteinized 32PO4 labeled HeLa cell total RNA. By competitive radioimmunoprecipitation assays, an experimentally induced anti-2,2,7 trimethylguanosine (TMG) cap structure mAb inhibited the reaction of these antisera. In addition, IgG isolated from the antisera inhibited the anti-TMG mAb reaction to the U snRNA. Furthermore, a structural analog, 7-methylguanosine triphosphate, competitively inhibited the reaction of the antisera to the U snRNA. Thus we concluded that the TMG cap structure of the U snRNA could be a target for serum autoantibodies. PMID- 1634765 TI - Selective breeding of miniature swine leads to an increased rate of acceptance of MHC-identical, but not of class I-disparate, renal allografts. AB - Previous work from this laboratory demonstrated that tolerance to MHC-identical or class I-disparate renal allografts develops in approximately one third of miniature swine without exogenous immunosuppression. A back-cross study indicated that rejection of MHC-identical transplants due to minor Ag was controlled by one or possibly two non-MHC-linked, autosomal dominant Ir genes. According to this hypothesis, and assuming complete penetrance, graft acceptors would be homozygous recessive at the relevant Ir loci, as would their offspring. Alternatively, if the gene(s) were incompletely penetrant, then two acceptors could give rise to a rejector. However, a high rate of MHC-identical graft acceptance would still be expected in the offspring of acceptors even if the Ir gene(s) were incompletely penetrant. To test this hypothesis and to obtain a higher frequency of acceptor animals for studies of tolerance, a program of selective breeding of renal allograft acceptors was begun. In the present paper, we assess the effect of selective breeding on renal graft acceptance. The analysis indicates a marked increase in the rate of MHC-identical graft acceptance, from 27.3% (n = 24) for the earliest of the four chronologic subgroups assessed to 64.5% (n = 33) for the most recent subgroup (p less than 0.0001). Calculations of kinship revealed that the increased acceptance of MHC-identical grafts was not the result of differences between acceptors and rejectors in donor/recipient consanguinity. Class I-disparate grafts (n = 128) were similarly stratified chronologically and compared. Unlike MHC-identical grafts, the rate of acceptance of class I disparate grafts has not changed over time. We conclude that rejector/acceptor status with respect to class I MHC incompatibility is determined by genetic factors in addition to those that control responses to minor antigen incompatibilities only. PMID- 1634766 TI - Shedding of the CD44 adhesion molecule from leukocytes induced by anti-CD44 monoclonal antibody simulating the effect of a natural receptor ligand. AB - The CD44 adhesion molecule, playing an important role in leukocyte extravasation, was down-regulated by PMA and ionomycin on granulocytes and by an immobilized or soluble anti-CD44 mAb both on granulocytes and lymphocytes. Soluble labeled CD44 molecules of lower apparent molecular mass as compared to their membrane counterparts were isolated from culture supernatants of stimulated surface iodinated cells. Shedding rather than internalization is the mechanism found to be responsible for the loss of CD44 from the cell surface. The size of the soluble CD44 shed from the cells stimulated in vitro corresponds to soluble CD44 isolated from human serum. These data suggest that shedding, induced by anti-CD44 antibody simulating the effect of a natural CD44 ligand, is an important regulatory mechanism controlling surface CD44 expression on leukocytes in vivo. PMID- 1634767 TI - MHC class II deletion mutant expresses normal levels of transgene encoded class II molecules that have abnormal conformation and impaired antigen presentation ability. AB - Successive transfers of HLA-DR alpha and beta genes restored expression of HLA-DR antigens to human B-lymphoblastoid cell line, LCL .174, from which all known expressible class II genes are deleted. While transferent cells displayed large amounts of DR on their surfaces, transgene-encoded DR3 molecules lacked a conformation-dependent epitope. DR1-restricted CTL lysis of DR1-expressing transferents pulsed with native influenza virus proteins was greatly reduced; the same cells were efficiently lysed in the presence of CTL-recognized influenza peptides. The properties of DR-expressing transferents of .174 suggest they are defective in producing peptides from exogenous proteins or in forming DR/peptide complexes. Comparison with other DR-expressing deletion mutants indicates that at least one gene in an approximately 230 kb DNA segment between the DQ1 and Ring 7 loci is needed for normal DR-mediated processing and presentation. Production of DR3 molecules having the conformation-dependent 16.23 epitope and efficient DR1 restricted presentation of influenza viral epitopes occurred in a B cell line that has a mutation specifically eliminating expression of the TAP1 transporter gene, which is in the approximately 230 kb interval and is needed for production of HLA class I/peptide complexes. PMID- 1634768 TI - Dual mechanisms of potentiation of murine antigen-specific IgE production by cyclosporin A in vitro. AB - Concomitant administration of cyclosporin A (CsA) with Ag has been shown to augment the production of Ag-specific IgE in vivo. We demonstrate that addition of CsA also markedly potentiated Ag-specific IgE in vitro. Low doses of CsA (3 and 10 ng/ml) added at the time of culture initiation selectively enhanced Ag specific IgE but not IgA or IgG1 production, whereas higher doses (30 ng/ml) suppressed production of all the isotypes. Augmented IgE production was found to correlate with enhanced production of IL-4 and diminished production of IFN gamma. Delayed addition (after 2 days) of low doses of CsA to Ag-stimulated cultures did not potentiate IgE production, even though CsA differentially affected levels of IL-4 and IFN-gamma. CsA enhanced Ag-mediated cognate T/B interaction was not affected by neutralizing doses of anti-IL-4, suggesting Ag mediated lymphocytic "synapses" may be inaccessible to anti-IL-4. The effect of CsA on Ag presentation was determined by pulsing peritoneal exudate cells, spleen cells, or primed B cells with Ag and low doses of CsA before incubation with primed splenocytes. Enhanced Ag-specific IgE responses were detected with no effect on IL-4 or IFN-gamma levels. Thus, our study indicates that CsA potentiation of Ag-specific IgE response is due to cumulative action of CsA on two independent pathways: first, CsA differentially modulates IL-4 and IFN-gamma levels during the early phase of cognate Th2/B cell interaction; and second, CsA directly affects APC and IgE isotype-specific amplifying cellular components without apparently affecting the secretory levels of IL-4 and IFN-gamma. Dual mechanisms of CsA-potentiated IgE production are consistent with the hypothesis of two-tiered T cell regulation of Ag-specific IgE responses. PMID- 1634769 TI - Selective functional depletion of HIV gp120 peptides complexed with MHC from antigen-presenting cells engaged with specific T lymphocytes. AB - Human T cell lines specific for different peptides of HIV envelope glycoprotein gp120 have been used as probes to identify the availability of functional MHC peptide complexes on APC. MHC-peptide complexes recognized by T cells specific for peptide 24 (amino acids 225-240) are no longer available on the surface of APC after interaction with irradiated (binding nonproliferating) T cells with the same fine specificity. On the contrary, MHC-peptide complexes recognized by T cells specific for peptide 30 (amino acids 285-300) were functionally available and could stimulate T cells with such a specificity. The reciprocal experiment yielded similar results. The same data were also reproduced with another pair of gp120 peptides. These data demonstrate that upon clustering of peptide-specific T cells with presenting cells presentation of the same peptide to a second cohort of T cells with identical specificity is abolished, suggesting that a selective functional depletion of the MHC-peptide complexes engaged with specific T cells occurs at the surface of the presenting cells. The depletion does not affect other MHC molecules complexed with unrelated peptides. PMID- 1634770 TI - Surface Ig receptor-induced nuclear AP-1-dependent gene expression in B lymphocytes. AB - The relationship between signals generated via the sIgR complex of B lymphocytes and subsequent changes in gene expression is poorly understood at the molecular level. To illuminate mechanisms that may couple these events, we examined the expression and function of tetradecanoyl phorbol acetate-response element (TRE) binding proteins (i.e., activator protein 1, (AP-1)) in the murine B lymphoma cell line BAL-17.7.1 (BAL-17), which models primary B lymphocyte responses in a number of respects. Cross-linking of sIgR led to substantial induction of nuclear AP-1, in BAL-17 B cells, that bound the TRE, as detected by electrophoretic mobility shift assay. The sIgR-induced TRE-binding activity consisted of both Jun and Fos proteins, on the basis of immunoreactivity of nucleoprotein complexes with specific antisera. In addition, immunoprecipitation with specific antisera showed that de novo synthesis of Jun-B and c-Jun proteins, accompanied by c-Fos, was stimulated after cross-linking of sIgR on BAL-17 B cells. Transient transfection of BAL-17 B cells with reporter gene constructs showed that B cell AP-1 failed to trans-activate the TRE-containing human collagenase gene promoter, for which activity is dependent upon functional expression of cellular c-Jun. In contrast, sIg-induced AP-1 trans-activated a HSV-tk promoter that contained three TRE; this pattern of gene expression is consistent with the presence of functional Jun-B-containing AP-1 in B lymphocytes. These results are the first to attribute a functional role to sIgR-mediated AP-1 in B lymphoid cells and suggest that AP-1 functions to couple the sIgR complex to changes in nuclear gene expression. PMID- 1634771 TI - Transcription and recombination of the murine RS element. AB - The deletion of C kappa is a frequent event in lambda-producing B cells in both mice and humans. Deletions of the murine C kappa gene are mediated by recombination events that involve the RS (recombining segment) element located downstream of the C kappa gene. RS recombinations appear to be mediated by the same mechanisms involved in Ig and TCR gene rearrangement. It has been suggested that RS recombinations might activate a factor that is involved in the initiation of lambda gene rearrangement in maturing pre-B cells. We have identified a unique RNA transcript derived from the recombined RS element present in some pre-B cell lines. However, gene transfer studies indicate that this RS transcript is not sufficient to induce lambda gene recombination in pre-B cell lines. We also find that recombination of the RS element in pre-B cell lines is closely correlated with changes in chromatin structure and transcriptional activation. Thus, recombination of the RS element in pre-B cells appears to be regulated in a manner similar to the regulation of antibody gene VDJ joining. PMID- 1634772 TI - Structure and expression of class II alpha genes in miniature swine. AB - Two overlapping genomic clones corresponding to the swine DRA class II gene were isolated and characterized. Restriction mapping and partial sequence data of the exon-containing fragments allowed identification and orientation of the five exons encoding the alpha chain. Two full length cDNA clones corresponding to the transcribed DRA gene from two different haplotypes of the swine MHC were sequenced. Nucleotide sequence alignments revealed that the two swine DRA cDNA were very similar and closely related to the human DRA equivalent. An additional glycosylation site, compared with those of human DRA, was found in the second external domain of the protein. Northern analyses showed that porcine DRA and DQA genes were the only two class II alpha genes expressed in the spleen, despite the presence of DPA and DZA genes in the genome. In addition to transfected cells expressing homologous pairs of alpha and beta chains from SLA-DR, stable transfectants expressing nonhomologous pairs of alpha and beta chains from DR and DQ loci were obtained, suggesting that such associations may contribute to the functional heterogeneity of class II products. PMID- 1634773 TI - Human leukocyte activation antigen M6, a member of the Ig superfamily, is the species homologue of rat OX-47, mouse basigin, and chicken HT7 molecule. AB - Peripheral granulocytes from rheumatoid arthritis and reactive arthritis patients were recently found to express higher levels of a newly defined Ag, termed M6, in comparison to granulocytes from healthy subjects. We present here the molecular characterization of M6 Ag and show that it is a novel human leukocyte activation associated cell surface glycoprotein. Peripheral lymphocytes do not significantly express M6 Ag, however, it appears upon 3-day PHA-activated T blasts. On monocytes, which constitutively express M6 Ag, it is down-regulated on day 1 but re-induced on day 3 of granulocyte-macrophage CSF stimulation. SDS-PAGE analysis of M6 immunoprecipitates shows a single band of 54 kDa under nonreducing conditions that shifts to 65 kDa under reducing conditions. Endoglycosidase F treatment of M6 immunoprecipitate reveals that 50% of the M6 molecule is composed of N-linked carbohydrates. By modifying the COS cell cloning strategy, we have isolated cDNA clones encoding M6 Ag. M6 cDNA hybridizes with a single mRNA transcript of approximately 1.7 kb in Northern blotting. Comparison analysis of the M6 sequence indicates that M6 Ag is a member of the Ig superfamily and the species homologue of rat OX-47 Ag, mouse basigin (gp42), and chicken HT7 molecule. The highly conserved remarkable transmembrane domain suggests that the M6 Ag may be a component of a multichain complex in the plasma membrane. PMID- 1634774 TI - Chicken IgA H chains. Implications concerning the evolution of H chain genes. AB - A cDNA clone (A1) encoding for a novel chicken Ig H chain isotype was isolated. In sequence comparison to mammalian H chains, A1 C region was most closely related to the alpha isotype. For example, identities of 35%, 32%, and 31% at the amino acid level to rabbit C alpha, C mu, and C gamma were observed, respectively. Distribution of the glucosamine acceptor sites (Asn-X-Ser/Thr) in A1 C region was typical of alpha H chains. Moreover, A1 C region probe hybridized to a 2.2-kb RNA species expressed in the epithelial lymphoid tissues. Thus, A1 was identified as the avian homologue for mammalian alpha H chains. Interestingly, the chicken C alpha was structurally consistent with four complete CH domains, whereas only three domains are present in the mammalian C alpha genes. In addition, interdomain sequence alignments suggested that the homologue for the chicken C alpha 2 domain is missing from the mammalian alpha H chains. Thus, the present data suggest evolution of the IgA isotype before the segregation of avian and mammalian species. Also, the first C alpha gene may have consisted of four CH domains, whereas reorganization of the C alpha 2 region led to the generation of hinge region in the mammalian alpha H chains. PMID- 1634775 TI - The rat mast cell antigen AD1 (homologue to human CD63 or melanoma antigen ME491) is expressed in other cells in culture. AB - Previously we reported that the mAb AD1 recognized a heavily glycosylated 50- to 60-kDa protein (AD1 Ag) sterically close to the high-affinity IgE receptor on rat basophilic leukemia (RBL-2H3) cells. The N-terminal amino acid sequence of the AD1 Ag was nearly identical to that of human CD63 (melanoma-associated Ag ME491). In this study we cloned the cDNA of AD1 Ag from a rat basophilic leukemia 2H3 cDNA library. An open reading frame of 238 amino acids was identified that contained the N-terminal 43 amino acid sequence. No evidence of a signal peptide was found. However, four predominantly hydrophobic stretches of sequence were predicted to form membrane-spanning helices, and three putative N-glycosylation sites were identified. The AD1 Ag and CD63 were highly conserved between rat and human, suggesting that the sequence of this protein is important for its function. By immunostaining various rat tissues, the AD1 Ag was found localized to mast cells. However, it was located to lysosomes, secretory granules and the plasma membrane of RBL-2H3 cells and to lysosomes and plasma membrane of many other cultured cell lines. The AD1 Ag could be induced by placing cells in culture. Fibroblasts and hepatocytes freshly isolated from rat embryos stained very weakly for AD1 Ag; however, after 24 to 48 h in culture they were strongly positive. This increase in the expression of the AD1 Ag was accompanied by an increase in detectable RNA message. Therefore, AD1/ME491/CD63 Ag is a mast cell marker in tissue, but is also associated with other cells in culture. PMID- 1634776 TI - A novel DNA binding activity is elevated in thymocytes expressing high levels of H-2Dd after radiation leukemia virus infection. AB - Resistance to radiation leukemia virus-induced leukemia is mediated by gene(s) in the H-2D region of the MHC; a clear correlation exists between disease resistance and increased H-2Dd expression on the thymocyte surface. We have investigated the molecular basis for this stimulation of H-2Dd class I expression. Elevated H-2 mRNA and H-2 transcription are demonstrated in the infected thymocytes as compared to normal thymocytes indicating that the elevation of H-2 surface expression is the result of transcriptional activation. Gel mobility assays performed with nuclear extracts of normal and infected thymocytes and sequences 5' of the H-2Dd gene show that specific binding occurs with both extracts; the binding differs both quantitatively and qualitatively, however. DNase I protection analysis detects a protein binding site that is protected only by extracts from infected cells. The protected region contains a sequence similar to the AP-1 consensus sequence. Gel shift competition assays and UV photo-cross linking to an oligonucleotide containing this sequence demonstrate that specific binding of an H-2 binding factor 1 occurs and that this factor is not the AP-1 binding complex. This novel binding factor, activated in vivo, might also be involved in the normal regulation of H-2 gene expression by recognizing the highly conserved binding sequence (TGACGCG) found in the 5' flanking region of many MHC class I genes. This is the first demonstration of the parallel stimulation of a DNA binding activity and increased transcription occurring in thymocytes after infection with a leukemogenic retrovirus. PMID- 1634777 TI - Extensive polymorphism in the extracellular domain of the mouse B cell differentiation antigen Lyb-2/CD72. AB - Lyb-2/CD72 is a 45-kDa mouse B cell surface protein that binds CD5 and has been shown to play a role in B cell proliferation and differentiation. Using the polymerase chain reaction we have isolated and sequenced cDNA clones encoding the serologically defined mouse Lyb-2a, Lyb-2b, and Lyb-2c alleles. We confirmed that our full length cDNA clones encode the Lyb-2a, -2b, and -2c alleles, respectively, by transfecting the isolated Lyb-2/CD72 cDNA clones into L cells and demonstrating that the transfectants bind only the appropriate allele specific anti-Lyb-2/CD72 antibodies. Sequence comparisons demonstrate that the Lyb-2/CD72 allels are highly conserved in their cytoplasmic and transmembrane domains but exhibit a high degree of polymorphism in their extracellular domains. This polymorphism in the extracellular region involves amino acid substitutions at a minimum of 20 residues and is concentrated primarily in the membrane distal region. cDNA sequence comparisons also demonstrate two distinct seven amino acid insertion/deletions among these allelic variants. A form of Lyb-2b cDNA lacking the sequence encoding the transmembrane region was isolated from a C57B1/6 mouse and a CH12.LX subline. The Lyb-2/CD72 PCR products from mRNA of mice expressing Lyb-2a and Lyb-2c contain a DNA fragment that corresponds in size to the transmembraneless form, suggesting that these mouse strains also express this mRNA. PMID- 1634778 TI - Naturally acquired CD8+ cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein. AB - In rodent malaria model systems, protective immunity induced by immunization with irradiated sporozoites is eliminated by in vivo depletion of CD8+ T cells, and adoptive transfer of CTL clones against the circumsporozoite protein protects against malaria. We recently demonstrated that volunteers immunized with irradiated Plasmodium falciparum sporozoites produce CTL against peptide 368-390 of the P. falciparum circumsporozoite protein. To determine whether natural exposure to malaria induced similar CTL, we studied 11 adult, male, life-long residents of a highly malarious area of Kenya, who were selected because their lymphocytes had been shown to proliferate after stimulation with peptides 361 380, 371-390, or 368-390 and because nine had been resistant to malaria in previous studies. In four of the 11 individuals there was peptide-specific, genetically restricted, CTL activity. In all four individuals, this activity was unaffected by depletion of CD4+ T cells. In three volunteers the activity was eliminated or reduced by depletion of CD8+ T cells; in the fourth volunteer the CD8+ T cell depletion was uninterpretable. This first demonstration of CD8+ T cell, genetically restricted, Ag-specific CTL against a malaria protein among individuals exposed to endemic malaria provides a foundation for studying the relationship between circulating CTL and resistance to malaria infection. PMID- 1634779 TI - Discrepancy between in vitro measurable and in vivo virus neutralizing cytotoxic T cell reactivities. Low T cell receptor specificity and avidity sufficient for in vitro proliferation or cytotoxicity to peptide-coated target cells but not for in vivo protection. AB - The TCR-alpha beta of CTL recognize peptide Ag in association with MHC class I molecules. TCR binding should be highly specific to guarantee pathogen specificity and to avoid self-reactivity. Therefore, the in vivo relevance of T cells exhibiting cross-reactivities in vitro and the respective role of the TCR affinities involved are not clear. To analyze high and low avidity T cell activities both in vitro and in vivo, we investigated primary and clonal CTL responses specific for the lymphocytic choriomeningitis virus nucleoprotein 118 126 epitope in association with the two closely related H-2Ld or H-2Lq molecules. As expected, we found highly specific class I-allele-restricted CTL responses when antiviral protection or immunopathology in vivo and lysis of virus infected target cells in vitro were analyzed. In contrast, the CTL were MHC crossreactive and thus considerably less discriminatory against targets expressing high MHC peptide densities and in proliferation assays. The data show that relatively high TCR avidities are required for virus neutralization in vivo, in contrast to in vitro analyses of peptide-coated target cells or proliferative T cell responses that may engage TCR of low avidity and broad specificity and therefore may not reflect biologically relevant TCR avidities. PMID- 1634780 TI - Cross-protection against influenza virus infection afforded by trivalent inactivated vaccines inoculated intranasally with cholera toxin B subunit. AB - Cross-protection against influenza virus infection was examined in mice, immunized intranasally with a nasal site-restricted volume of inactivated vaccines together with cholera toxin B subunit (CTB) as an adjuvant. The mice were challenged with either a small or a large volume of mouse-adapted virus suspension, each of which gave virgin mice either a predominant upper or lower respiratory tract infection. A single dose of a monovalent influenza A H3N2 virus vaccine with CTB provided complete cross-protection against the small-volume challenge with a drift virus within the same subtype, but a slight cross protection against the large-volume challenge. A second dose of another drift virus vaccine increased the efficacy of cross-protection against the large-volume challenge. Similar cross-protection against H1N1, H3N2, or B type drift virus challenge was provided in the mice having received a primary dose of a mixture of H1N1, H3N2, and B virus vaccines with CTB and a second dose of another trivalent vaccine. The degree of cross-protection against the small- and the large-volume infection paralleled mainly the amount of cross-reacting IgA antibodies to challenge virus hemagglutinin in the nasal wash and that of cross-reacting IgG antibodies in the bronchoalveolar wash, respectively. On the other hand, in mice immunized subcutaneously with the trivalent vaccines having no cross-reacting IgA antibodies, the efficacy of cross-protection was not so high as that of nasal vaccination. These results suggest that the nasal inoculation of trivalent vaccines with CTB provides cross-protection against a broader range of viruses than does the current parenteral vaccination. PMID- 1634781 TI - Surgery in rheumatoid arthritis. PMID- 1634782 TI - Blindness in India. PMID- 1634783 TI - Bladder rehabilitation in spinal cord injury patients. AB - The relative efficacy of intermittent catheterisation, self or assisted, over indwelling catheterisation was studied on 44 patients of different extent of spinal cord lesions. All the surviving cases (9) of incomplete cord lesion became catheter free irrespective of the method of catheterisation. In these patients urine was also found to be infection free by the 5th week of admission. Twenty seven cases of complete cord lesion (out of a total of 35) became catheter free, of whom 18 patients were on intermittent catheterisation (out of a total of 20) and 9 patients were on indwelling catheter (out of a total of 15 cases). In the later group incidence of urine infection was higher. Other complications like urethral trauma were comparable between patients with indwelling catheter and patients with intermittent, self or assisted, catheterisation. PMID- 1634784 TI - Low dose ketamine: an ideal supplementary anaesthesia for spinal block. AB - In a double blind clinical trial 100 adult patients were randomly divided into 2 groups. In group I after spinal block slow injection of diazepam (0.1 mg/kg) was followed by placebo (0.5 mg/kg as bolus and 0.5 mg/kg/hour in infusion). In group II patients, after spinal block slow injection of diazepam (0.1 mg/kg) was followed by injection of ketamine (0.5 mg/kg as bolus and 0.5 mg/kg/hour as infusion). Low dose of ketamine in combination with diazepam significantly improves quality of anaesthesia, gives better cardiovascular stability without significant increase in complication rate and significantly improves patients' acceptance for the technique. PMID- 1634785 TI - Epidemiology of rheumatic and congenital heart diseases in school children. AB - A stratified random sample of 10,263 school-going children in the age group of 6 16 years from government and private schools were screened for the prevalence of rheumatic fever, rheumatic heart diseases and congenital heart diseases. Fourteen children were found to have rheumatic heart disease with valvular lesions either single or in combination eg, pure mitral stenosis (6 cases), mitral regurgitation (4 cases), combined mitral stenosis and mitral regurgitation (3 cases) and aortic and mitral regurgitation (one case). Eight children had congenital heart diseases in the form of ventricular septal defect (3 cases), atrial septal defect (2 cases), patent ductus arteriosus (2 cases) and congenital bicuspid aortic valve (one case) while none had active rheumatic fever. PMID- 1634786 TI - Anti-amoebic antibody levels in gastro-intestinal disorders. AB - Serum anti-amoebic antibody levels were studied in 91 cases having clinical presentation of bowel disorders and 31 cases of control. Anti-amoebic antibody was positive in significant dilutions in 38 cases (31.15%) in total comprising 9 cases out of 22 cases showing presence of Ent histolytica cyst in stool, 13 cases who were positive for ova, parasite and cysts other than Ent histolytica in stool and 16 cases out of 70 cases with negative stool findings. It was positive in 5 cases out of 9 diagnosed cases of amoebic liver abscess. Assessment of immunoglobulin levels in amoebic liver abscess cases revealed high levels of immunoglobulin G and immunoglobulin M. PMID- 1634787 TI - Gastric cancer: a critical analysis of surgical treatment and long term survival. AB - Results of consecutive study of 120 cases of carcinoma stomach treated by one surgical team over a period of 10 years (1980-89) are presented. Maximum cases were in the sixth and seventh decades with male to female sex ratio of 2.5:1. The lesion in most cases were in the gastric antrum. Distal tumours were more of poorly differentiated histology compared to proximal tumours. Eighty-three out of 120 (69%) patients underwent surgical resection. In 50 patients it was in the form of a subtotal and distal gastrectomy. Only 5 patients underwent a total gastrectomy. In 70 cases the resection which involved en bloc removal of involved part of stomach including adequate proximal and distal free margins, omenta and perigastric lymph nodes and considered absolutely curative in 8 cases being no disease. The overall 5-year-survival figure was 18%. However, taking only the resected cases into account, the 5-year survival rate was 27%. The low survival figure can be attributed to a very small number of early cases encountered. PMID- 1634788 TI - Effect of clinicobiochemical bias on the sensitivity of nuclear imaging in detecting hepatic malignancies. AB - A retrospective analysis of the sensitivity of nuclear imaging in detecting hepatic malignancies has been done. Effects of clinical and liver function test bias have been studied on the ascribed sensitivity. The clinicobiochemical bias raises the detection sensitivity from 66.7% to 90.7% (p less than 0.001) but decreases the specificity of nuclear imaging significantly (p less than 0.05). PMID- 1634789 TI - Postcaesarean wound infection: a review of risk factors. AB - In a prospective study of 431 cases delivered by caesarean section, wound infection developed in 54 (12.52%) cases. In 2.55% cases, infection was deep with drainage of purulent material. The factors associated with a high risk of wound infection were anaemia, multiple pelvic examinations, prolonged rupture of membranes and handling by dai. General ward cases had a significantly higher wound infection rate than the private ward cases. PMID- 1634790 TI - Primary multicentric carcinomas of kidney. PMID- 1634791 TI - Ellis-van Creveld syndrome. PMID- 1634792 TI - Alveolar soft part sarcoma. PMID- 1634793 TI - Hospital administration in Calcutta. 1933. PMID- 1634794 TI - Epilepsy and pregnancy. PMID- 1634795 TI - Immunisation certificate. PMID- 1634796 TI - Q fever. PMID- 1634797 TI - Sports medicine. PMID- 1634798 TI - Helmets and head injuries. PMID- 1634799 TI - Association of gastric hypoacidity with opportunistic enteric infections in patients with AIDS. AB - To determine the relation and possible significance of gastric hypoaciditity to chronic diarrhea in AIDS, patients with and without chronic (greater than 1 month) diarrhea underwent fasting gastric juice pH measurement and microbiologic study and upper and lower endoscopy with biopsy. All 8 patients with diarrhea and high gastric pH (greater than 3; mean, 6.1 +/- 1.0) had gastric bacterial overgrowth (greater than 10(4) bacteria/mL) along with opportunistic enteropathogens in the duodenum or rectosigmoid, but only 1 of 6 patients with diarrhea and gastric pH in the normal range (less than or equal to 3; mean, 1.9 +/- 0.7) had overgrowth or an opportunistic enteropathogen. By contrast, all but 1 of 9 controls (AIDS patients without diarrhea) had normal fasting gastric pH (mean, 2.9 +/- 1.5). Overall, the presence of gastric hypoacidity was associated with identification of opportunistic enteropathogens (P = .035). Thus, gastric hypoacidity is associated with quantitative bacterial overgrowth and opportunistic enteric infections and may be etiologically important in the pathophysiology of the chronic diarrhea seen in some AIDS patients. PMID- 1634800 TI - Effect of cyclosporin A and zidovudine on immune abnormalities observed in the murine acquired immunodeficiency syndrome. AB - Two therapeutic modalities, zidovudine (targeting retroviral replication) and cyclosporin A (targeting immunopathologic consequences of retroviral expression) were evaluated in a murine model of AIDS. In previous studies, cyclosporin A treatment (40 or 60 mg/kg/day) before and after infection with LP-BM5 murine leukemia viruses protected against the development of immunodeficiency disease. The present study extends these findings. First, a low dose of cyclosporin A (20 mg/kg/day) was ineffective, and treatment initiated 5 days after infection did not protect against virus-induced lymphoproliferation and hypergammaglobulinemia. Second, zidovudine added to drinking water (0.1 mg initiated 5 days after infection and continued for 8 weeks) was more effective than 0.2 mg/mL given day 5-12 after infection. This treatment reduced lymph node size, disease severity as determined histologically, retrovirus-induced gp70 expression, and IgE (but not IgM and IgG) levels. Third, combined treatment had an additive, protective effect on lymphocyte proliferative capacity. This successful dual therapeutic strategy in a mouse model has potential applicability for similar approaches in treating human immunodeficiency virus infection. PMID- 1634801 TI - Epidemiologic and historical relationships among 87 rabies virus isolates as determined by limited sequence analysis. AB - Nucleotide sequence analysis of a 200-bp region of the nucleoprotein (N) gene of rabies virus differentiated unique genetic groups of rabies virus from samples collected in areas where dog rabies is enzootic in Asia, Africa, Europe, and the Americas. Patterns of nucleotide sequence identified for an outbreak area were conserved in samples collected over three decades. Epidemiologic relationships among isolates were determined by patterns of conserved nucleotide sequence, and the degree of sequence divergence between samples from separate outbreak areas were measured. This approach suggested that a historical reconstruction of events leading to the introduction of rabies into an area would be possible. In this broader view of rabies epidemiology, the cultural legacy of European exploration and colonization may have also included zoonotic disease. PMID- 1634802 TI - Translocation of Campylobacter jejuni across human polarized epithelial cell monolayer cultures. AB - The ability of Campylobacter jejuni isolates to translocate across an epithelial cell barrier was investigated by using polarized Caco-2 cell monolayers grown on microporous membrane filters. The 4 C. jejuni isolates tested all traversed the Caco-2 cell monolayers and displayed similar translocation kinetics. The number of bacteria crossing the polarized cell monolayers continued to increase with time until 4 h after inoculation, at which time a maximum rate of translocation was observed. Transmission electron microscopy revealed that C. jejuni translocated across polarized Caco-2 cell monolayers by passing both through and between cells. Chloramphenicol, an inhibitor of bacterial protein synthesis, reduced the translocation of C. jejuni. Bacterial attachment, internalization, and translocation were inhibited at low temperature. These data indicate that adherence, penetration, and translocation of C. jejuni require active bacterial and target cell processes and further suggest a role for cellular translocation in the pathogenesis of C. jejuni-mediated enteritis. PMID- 1634803 TI - Trimethoprim-resistant Escherichia coli in households of children attending day care centers. AB - Children in day care centers are frequently colonized with trimethoprim-resistant Escherichia coli. The frequency of transmission to family members was studied. Colonization with trimethoprim-resistant E. coli was detected in 13 (57%) of 23 day care center children. Among the 50 (98%) of 51 household members tested, colonization was detected in 13 (26%), representing 12 (52%) of 23 households tested. Households of colonized center children had significantly more colonized members than did households of noncolonized children (odds ratio, 13.3; 95% confidence interval, 1.3-172.6; P = .01). There was a trend toward higher prevalence of colonization in mothers (35%) and siblings (30%) than in fathers (12%). The same plasmid profiles of trimethoprim-resistant E. coli from center children were found among 8 (67%) of 12 colonized households. There was no association between antibiotic use and fecal colonization with trimethoprim resistant E. coli. Thus, transmission of trimethoprim-resistant E. coli among children within day care centers and from center children to household members is common. PMID- 1634804 TI - Role of interferon-gamma in experimental gram-negative sepsis. AB - To study the role of interferon-gamma (IFN-gamma) in gram-negative shock, mortality was compared in mice receiving either a monoclonal antibody to IFN gamma (H22) or an irrelevant monoclonal antibody (L2-3D9) before or after an LD90 dose of Escherichia coli O111:B4. H22 given either 1 h before or 0.5 h after bacterial challenge protected mice from death (mortality at 48 h, 28% vs. 83%, P less than .001). Serum tumor necrosis factor-alpha (TNF alpha) levels and bacterial counts in blood and organs (liver, spleen, heart, and brain) were similar in H22-treated animals and controls. The peak serum TNF alpha levels were 95.7 +/- 16.4 ng/mL and 80.7 +/- 14.9 ng/mL in the H22 and control groups, respectively. These results indicate that IFN-gamma plays a significant role in the pathogenesis of gram-negative sepsis. PMID- 1634805 TI - Affinity constants of naturally acquired and vaccine-induced anti-Pseudomonas aeruginosa antibodies in healthy adults and cystic fibrosis patients. AB - Naturally acquired anti-Pseudomonas aeruginosa antibody fails to afford protection against repeated P. aeruginosa bronchopulmonary exacerbations in cystic fibrosis (CF) patients. In an effort to explain this phenomenon, the titer and affinity constants of serum anti-lipopolysaccharide (LPS) IgG were determined in five study groups: healthy adults before and after immunization with a polyvalent LPS-based vaccine, healthy noncolonized CF patients before and after immunization, nonimmunized CF patients with significantly elevated anti-LPS antibody titers without documented colonization, recently colonized CF patients before and after immunization, and nonimmunized CF patients chronically colonized with P. aeruginosa. Immunization elicited a significant rise in total anti-LPS immunoglobulin levels and affinity constants in both healthy adults and CF patients. Although chronically colonized patients had elevated levels of total anti-LPS antibody, these antibodies possessed affinities at least 100-fold less than those of vaccine-induced antibodies. PMID- 1634806 TI - Blood-brain barrier damage in patients with bacterial meningitis: association with tumor necrosis factor-alpha but not interleukin-1 beta. AB - Brain damage after meningeal infection could result from impairment of cerebral endothelial cell functions and disruption of blood-brain barriers. Tumor necrosis factor-alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) produce many of their effects by acting on endothelial cells. This study correlates levels of TNF alpha and IL-1 beta in paired cerebrospinal fluid (CSF) and serum samples with the degree of blood-brain barrier damage, as manifested by CSF to serum albumin quotient, in 48 patients with bacterial meningitis and 66 controls. CSF levels of TNF alpha and IL-1 beta in bacterial meningitis were significantly higher than in controls. Intrathecal levels of TNF alpha, but not IL-1 beta, correlated with albumin quotient (P less than .001), with degree of blood-brain barrier disruption (P less than .001), and with disease severity and indices of meningeal inflammation. Sequential CSF samples demonstrated that IL-1 beta and TNF alpha disappear from the CSF within 24 h of antibiotic treatment. Data presented here suggest that TNF alpha is related to blood-brain barrier damage in bacterial meningitis and that its effect could be dissociated from that of IL-1 beta. PMID- 1634807 TI - Epidemic meningococcal disease in Nairobi, Kenya, 1989. The Kenya/Centers for Disease Control (CDC) Meningitis Study Group. AB - An epidemic of meningococcal disease occurred in Nairobi, Kenya, during 1989, outside the "meningitis belt" of sub-Saharan Africa. About 3800 cases occurred between April and November (250/100,000 population). The case-fatality rate was 9.4% among hospitalized patients. Areas that included Nairobi's largest slums had particularly high attack rates. The epidemic displayed an unusual age distribution, with high attack rates among those 20-29 years old. A vaccination campaign was conducted. By early January, the weekly case count had fallen to 25 from a high of 272 (in September). A case-control study estimated the vaccine efficacy to be 87% (95% confidence interval, 67%-95%). A model estimated that the vaccination campaign reduced the number of cases by at least 20%. Multilocus enzyme electrophoretic typing demonstrated that the strain responsible for this large epidemic is closely related to strains that caused other recent epidemics, documenting further spread of what may be a particularly virulent clonal complex of group A Neisseria meningitidis. PMID- 1634808 TI - Broad and persistent effects of benzathine penicillin G in the prevention of febrile, acute respiratory disease. AB - After an outbreak of acute rheumatic fever at a US Army training installation, a benzathine penicillin G prophylaxis program was instituted. Surveillance data were analyzed to measure rates of febrile, acute respiratory disease (ARD) among trainees before and after prophylaxis was begun. Annual admissions for ARD decreased from 1927 to 690 (-64.2%) after benzathine penicillin G prophylaxis was begun. Admissions with throat cultures positive for Streptococcus pyogenes fell from 595 to 63 (-89.4%), a reduction that accounted only for a minority (43%) of the total 1237 "prevented" admissions. Temporal changes in disease rates at other installations where drug was not administered were also analyzed. Only a small decrease in the number of annual ARD admissions (-6.3%) was observed at other training installations. These findings support a hypothesis that benzathine penicillin G has a broad effect in the prevention of ARD that extends beyond the simple elimination of group A streptococcal infection. PMID- 1634809 TI - Epidemiologic analysis of group A streptococcal serotypes associated with severe systemic infections, rheumatic fever, or uncomplicated pharyngitis. AB - More than 1100 group A streptococcal isolates collected in the United States (1988-1990) were examined to document an association of individual serotypes with specific clinical infections during the recent resurgence of group A infections and their sequelae. The most commonly isolated strains from patients with only uncomplicated streptococcal pharyngitis ("control" strains) were M serotypes 1, 2, 4, and 12. M1, M3, and M18 were statistically significantly more frequently isolated from patients with serious invasive infections and M3 and M18 from patients with rheumatic fever compared with the distribution of serotypes from the 866 control strains. An unexpected and important finding indicated that isolation rates of M1 streptococci varied geographically within the United States by year. The propensity for M1 streptococci to be statistically associated with severe systemic infections appeared unrelated to the M1 isolation rates from patients with only uncomplicated pharyngitis, thus offering additional support for the concept of strain-associated virulence rather than virulence broadly related to a given serotype. PMID- 1634810 TI - Comparison of the major outer membrane protein variant sequence regions of B/Ba isolates: a molecular epidemiologic approach to Chlamydia trachomatis infections. AB - The molecular evaluation of the chlamydial major outer membrane protein (MOMP) gene (omp1) can facilitate epidemiologic investigations of this pathogen. Genotyping of omp1 provides a more precise characterization of Chlamydia trachomatis than do current immunotyping techniques. Genetic omp1 variants of serovars that are responsible for ocular disease in Tunisia were identified. Archival conjunctival samples collected during 1972 and 1975 from trachoma patients in Douz were sequenced by automation along with additional B and Ba trachoma and genital isolates. Over 90% of the nucleotide changes resulted in an amino acid substitution. Different amino acid sequence changes in variable segments 1, 2, and 4 were found in the specimens collected in 1975 from those collected in 1972. Determination of omp1 genotypes responsible for trachoma will be useful for prospective, epidemiologic studies to identify chlamydial reservoirs within the host, evaluate transmission patterns, and determine the antigenic variation of MOMP for rational vaccine development. PMID- 1634811 TI - Low-inoculum model of surgical wound infection. AB - A model of surgical wound infection that uses low inocula of bacteria and closely simulates clinical infection involved inoculating suspensions of Staphylococcus aureus and dextran microbeads into intermuscular sites on the dorsum of guinea pigs, harvesting lesions at 72-96 h, identifying as a positive end point lesions yielding staphylococci on subculture, and using logistic regression for data analysis. Prophylaxis was placebo, ampicillin, or cefazolin, and three representative strains of S. aureus were used. A highly significant correlation (P less than .001) was observed between inoculum sizes and infection rates. Without antimicrobial prophylaxis, ID50 for each strain was less than 10 organisms; with antimicrobials, ID50 was significantly higher. Differences in the virulence of strains and in the efficacy of the antimicrobial regimens also were observed. The model should prove useful for understanding mechanisms of virulence among pathogenic bacteria and for elucidating subtle but important differences in efficacy among antibiotics used in prophylaxis. PMID- 1634812 TI - Comparison of in vitro adherence of methicillin-sensitive and methicillin resistant Staphylococcus aureus to human nasal epithelial cells. AB - Reported nasal carriage rates of personnel caring for patients with methicillin resistant Staphylococcus aureus (MRSA) range from 1% to 6% in contrast to nasal carriage rates of 45%-65% for methicillin-sensitive S. aureus (MSSA) in health care personnel under nonepidemic conditions. One proposed explanation for these conflicting observations was examined, namely that MSSA and MRSA differ in their ability to adhere to nasal epithelial cells. The adherence of 6 genotypically distinct strains of MSSA and MRSA to nasal epithelial cells from 5 healthy donors was compared using a radioisotope assay system (coefficient of variation, 26%). The effect of pretreating epithelial cells with S. aureus-derived ribitol teichoic acid, a known adhesin of S. aureus for epithelial cells, was also examined. The mean (+/- SE) adherence of MRSA compared with MSSA in 108 assays was 125 +/- 11.9 versus 129 +/- 8.3 viable bacteria per cell (P = .67). Dose dependent competitive inhibition by ribitol teichoic acid was linear and equivalent for MRSA and MSSA (r, .949, P less than .001). As these in vitro results correlate to adherence in vivo, it would be anticipated that MRSA and MSSA would have an equal likelihood of nasal carriage. A critical review of published epidemiologic studies comparing MRSA and MSSA carriage rates also supports this hypothesis. PMID- 1634813 TI - Intestinal parasite infection in the Kampuchean refugee population 6 years after resettlement in Canada. AB - A follow-up prevalence study was done in 1989 of the same Kampuchean refugee population (247 subjects) that had been screened and treated for intestinal parasite infection 6 years earlier. A control group (102 subjects) included Kampuchean refugees who had arrived in Montreal at about the same time. These groups did not differ in age, sex, family size, or number of months spent in refugee camps. Statistically significant prevalence differences were observed in the rescreened group between 1982-1983 (63.7%) and 1989 (21.9%) and between the rescreened group and the control group (39.2%). These differences are largely attributable to the elimination of Ascaris infection and decreases in Giardia and hookworm infections. However, Strongyloides infection decreased only slightly (from 15% to 11%) in the rescreened group, while 12% of the control group was infected. Despite an early screening and treatment program, there remain important health risks in this immigrant population due to long-lived potentially pathogenic parasites. PMID- 1634814 TI - Degree and length of viremia in adults with measles. AB - Measles viremia is thought to peak at onset of rash and diminish rapidly over the subsequent 2-3 days. The length of viremia and the proportion of peripheral blood mononuclear cells (PBMC) infected during measles were investigated in 8 adults. Blood was obtained from 7 patients between days 2 and 4 of rash. Five patients had repeat specimens obtained on day 6 or 7, and 1 patient had samples taken on days 6 and 10. Limiting dilutions of PBMC were cultivated with cord blood PBMC and stimulated with phytohemagglutinin. Virus was identified by syncytia formation and confirmed by immunofluorescent staining. Virus was isolated from all 8 patients. Four of 6 patients were still viremic at day 6 or 7 of rash. Titers ranged from 3 to 5623 TCID50/10(5) PBMC. Adults with measles may have prolonged viremia, and a large proportion of PBMC may be infected. PMID- 1634815 TI - High concentrations of intrathecal interleukin-6 in human bacterial and nonbacterial meningitis. AB - Interleukin-6 (IL-6) is multipotent cytokine that acts in a network of factors directing the inflammatory reaction of purulent bacterial meningitis (PBM). However, little is known about the role of IL-6 in aseptic or "viral" meningitis (AM). IL-6 was assayed by RIA in cerebrospinal fluid (CSF) and serum samples obtained from patients with AM (n = 65), PBM (n = 8), and lymphocytic bacterial meningitis (LBM, n = 11). Of patients with AM, 89% had detectable IL-6 in CSF, with high IL-6 titers (median, 2160 pg/mL; 95% confidence interval [CI], 1320 2540 pg/mL) compared with 100% in patients with PBM (median, 6575 pg/mL; 95% CI, 450-32,000 pg/mL) and 90.9% in patients with LBM (median, 875 pg/mL; 95% CI, 150 2180 pg/mL). There was a highly symmetrical correlation between IL-6 and the percentage of polymorphonuclear cells in CSF of patients with PBM (r = .97, P = .01) and AM (r = .49, P = .002). In conclusion, this study shows evidence that IL 6 is released into the meningeal space in aseptic meningitis and is correlated with the local acute inflammatory response. PMID- 1634816 TI - Fibroblasts protect the Lyme disease spirochete, Borrelia burgdorferi, from ceftriaxone in vitro. AB - The Lyme disease spirochete, Borrelia burgdorferi, can be recovered long after initial infection, even from antibiotic-treated patients, indicating that it resists eradication by host defense mechanisms and antibiotics. Since B. burgdorferi first infects skin, the possible protective effect of skin fibroblasts from an antibiotic commonly used to treat Lyme disease, ceftriaxone, was examined. Human foreskin fibroblasts protected B. burgdorferi from the lethal action of a 2-day exposure to ceftriaxone at 1 microgram/mL, 10-20 x MBC. In the absence of fibroblasts, organisms did not survive. Spirochetes were not protected from ceftriaxone by glutaraldehyde-fixed fibroblasts or fibroblast lysate, suggesting that a living cell was required. The ability of the organism to survive in the presence of fibroblasts was not related to its infectivity. Fibroblasts protected B. burgdorferi for at least 14 days of exposure to ceftriaxone. Mouse keratinocytes, HEp-2 cells, and Vero cells but not Caco-2 cells showed the same protective effect. Thus, several eukaryotic cell types provide the Lyme disease spirochete with a protective environment contributing to its long-term survival. PMID- 1634817 TI - Serum tumor necrosis factor in acute and fulminant hepatitis B. PMID- 1634818 TI - Safety and immunogenicity of Salmonella typhi Ty21a liquid formulation vaccine in 4- to 6-year-old Thai children. PMID- 1634819 TI - Serum interleukin-6 levels and adverse reactions to diethylcarbamazine in lymphatic filariasis. PMID- 1634820 TI - Clinical significance of tumor necrosis factor in patients with bronchogenic carcinoma and benign lung diseases: a comparative study. AB - Tumor Necrosis Factor (TNF) was determined in the serum of 72 lung carcinoma patients. Twenty-four healthy subjects younger than 50 years and 10 healthy subjects older than 70 years were considered as control group. TNF was also measured in 20 patients with stage I sarcoidosis and in 15 patients with pulmonary fibrosis. The marker was detected in 32% of cases in the neoplastic group, in 37.5% of disease confined to the chest and in 25% of advanced disease cases. A large proportion of TNF-positive samples was found in sarcoidosis (30%), and even larger in pulmonary fibrosis (66.6%). TNF was also present in healthy subjects older than 70 (40%). We conclude that TNF is not specific of malignancy, being demonstrable in other benign pulmonary diseases and even in the course of physiological aging. PMID- 1634821 TI - HER-2/neu gene in primary and local metastatic axillary lymph nodes in human breast tumors. AB - In order to verify whether the HER-2/neu gene is involved in the initial phases of neoplastic disease or in its progression, we evaluated the amplification and overexpression of this gene in the primary tumor and in synchronous metastatic axillary lymph nodes of 26 women with operable breast cancer. HER-2/neu was amplified in 35% and overexpressed in 33% of the primary sites; similar percentages were found in lymph nodes. The clear correlation between the two disease sites regarding gene, mRNA and protein levels, supports the hypothesis that this gene is involved in the initial and invasive phases of neoplasia. Its actual role with respect to other biological tumor characteristics during the metastatic process should be investigated further. PMID- 1634822 TI - Preliminary evaluation of HER-2/neu oncogene and epidermal growth factor receptor expression in normal and neoplastic human ovaries. AB - The HER-2/neu oncogene (a member of the Erb-like oncogene family) is distinct from but closely related to the c-erb B gene which encodes the epidermal growth factor receptor (EGFr). HER-2/neu gene amplification was found in a large number of mammary carcinomas and there was a strong correlation between this phenomenon and poor prognosis. In our study HER-2/neu oncogene expression was determined in 16 malignant ovarian tumors, 2 ovarian lymphomas and 5 normal ovaries. The HER 2/neu gene was found both in normal ovaries and malignant tumors, without any apparent difference among the various histological types. In all the specimens examined, HER-2/neu expression did not seem to be related to EGF binding capacity. PMID- 1634823 TI - Half-life of carcinoembryonic antigen following curative resection of adenocarcinoma of the lung. PMID- 1634824 TI - Total lactate dehydrogenase and tumor necrosis factor alpha levels in cyst fluid of women with gross cystic breast disease. PMID- 1634825 TI - CAM26 and CAM29 cytosol levels in breast tumors classified according to estrogen receptor status. First results. PMID- 1634826 TI - Plasma monomeric calcitonin as a marker of disease activity in multiple myeloma patients with osteolysis. AB - Circulating monomeric human calcitonin (hCT-M), parathyroid hormone, osteocalcin, alkaline phosphatase, urinary hydroxyproline, corrected serum calcium and inorganic phosphate were measured in 49 multiple myeloma patients and 49 matched controls. In patients with Durie-Salmon stage III disease hCT-M levels (16.9 +/- 5.8 ng/l, mean +/- SD) were significantly higher than controls and stage I patients (P less than 0.01), and correlated directly with corrected serum calcium (r = 0.74; P less than 0.001). In the same subgroup 14 of 15 patients had plasma hCT-M concentrations higher than the mean + 2SD of the controls. The calcium infusion test induced an increase of hCT-M in normocalcemic patients which was significantly greater in patients with advanced disease than in either controls or stage I patients. These findings suggest that hCT-M may be a biochemical index of bone resorption and disease activity in myeloma patients with osteolysis. In fact, its plasma concentrations were elevated in a large proportion (93%) of patients with severe bone involvement, and correlated directly with serum calcium. Moreover, our findings suggest the presence of a calcitonin-dependent calcium homeostatic mechanism, that protects against hypercalcemia due to tumor osteolysis. PMID- 1634827 TI - Growth fraction of colorectal carcinoma (Ki67): a comparative study. AB - We studied the growth fraction of 55 resected colorectal adenocarcinomas by means of a three-step immunoperoxidase technique (avidin-biotin-peroxidase) using the monoclonal antibody Ki67 directed against a cell proliferation-associated nuclear antigen. The percentage of Ki67-positive cells was evaluated independently by two observers, and a Ki67 score was obtained for each case. No correlation was observed between Ki67 staining and patient's age and sex, tumor size and localization or grading and staging according to Dukes' method (modified by Astler-Coller and Turnbull). The growth fraction showed extreme heterogeneity in the cases examined, within each grade of differentiation. PMID- 1634828 TI - [Right aortic arch with mirror-image branching and coarctation of the aorta--a case report]. AB - The right aortic arch with coarctation of the aorta was reported. A 56-year-old woman admitted to the hospital because of headache and hypertension. Cardiac catheterization revealed the right aortic arch with coarctation of the aorta and 80 mmHg pressure gradient across the coarctation. The bypass operation with a 14 mm Dacron graft between the ascending to descending aorta was performed. There was no peak systolic pressure gradient between the ascending and descending aorta after bypass operation. This patient is the fourth case report with both mirror image type right aortic arch and coarctation of the aorta. PMID- 1634829 TI - [Recurrent thromboses of the Bjork-Shiley valve in a patient with gout]. AB - A 56-year-old male, who had mitral stenosis and gout, underwent mitral valve replacement with the Bjork-Shiley valve prosthesis. Four years after the surgery, the patient suddenly became dyspneic on exercise due to malfunctioning valve. Thrombosis was found on the prosthesis, which was replaced again by Bjork-Shiley valve. Thrombotest value had been satisfactorily controlled at 12.8 +/- 4.2% with warfarin since the first surgery. Dilazep chlorate also had been prescribed. Hyperuricemia had been controlled with allopurinol. In spite of these combined medical therapy, thrombosed valve recurred. Clotted prosthesis was superseded by Carpentier-Edwards Bioprosthesis. Enhancement of platelet function of the patients with gout and hyperuricemia has been reported. Gout in this case might have influence on the recurrent episodes of thrombosis. Monitoring of platelet function would be necessary in follow-up of a patients with gout and valve replacement. PMID- 1634830 TI - [A case of a primary neurofibroma of the left ventricle]. AB - A neurogenic tumor of the heart is extremely rare, and previously only 8 cases of malignant schwannoma and 3 cases of neurilemmoma have been reported. The patient of this case was a seven year old boy and referred to our hospital by his school doctor for investigation of IRBBB on screening ECG. The chest-X-ray showed a bulging contour on left ventricular apex. Echocardiography and angiography showed a 4 x 4 cm solid mass in the anterior-lateral wall of the left ventricle near the apex. Thoracotomy was performed and during cardiopulmonary bypass the tumor was successfully removed without involvement of the endocardium. It was not encapsulated. The pathohistological findings of the specimen were compatible with neurofibroma, and S-100 protein was demonstrated immunohistochemically. PMID- 1634831 TI - [Surgical treatment of Candida endocarditis involving mitral valve--a case report]. AB - A 53-year-old male with a low pulmonary function (FEV1.0 500 ml) and cachexia was admitted for a remittent fever. Blood culture along with echocardiography indicating vegetation on the anterior mitral leaflet confirmed Candida endocarditis involving mitral valve. Following anti-fungal drug therapy, mitral valve replacement was performed. Surgical specimen of mitral valve showed vegetation on the anterior mitral leaflet with Candida albicans. The post operative course was uneventful, through the anti-fungal drug therapy was compelled to be discontinued owing to drug allergy. He was discharged on the 67th postoperative day. There was no evidence of recurrence without medication for 9 months after his discharge. PMID- 1634832 TI - [Biventricular repair for right isomerism associated with transposition of great arteries and common atrioventricular canal]. AB - A 5-years old boy, whose thoracic situs was right isomerism, was diagnosed as transposition of great arteries, common atrioventricular canal (intermediate type), severe tricuspid valve regurgitation, pulmonary valve stenosis, bilateral superior vena cava and left sided inferior vena cava. The preoperative RVEDV was 95% and LVEDV 160%, and LV/RV pressure ratio was 0.54. Atrial rerouting using pericardial patch, replacement of tricuspid valve and pulmonary valvotomy were performed. Postoperative course was uneventful. This was a rare case of right isomerism who received biventricular repair. PMID- 1634833 TI - [A case report of surgical repair of aneurysm involving the distal arch and the descending aorta through median sternotomy]. AB - A 46-year-old male patient with aneurysm involving the distal arch and the descending aorta was operated on successfully. Graft replacement of aneurysm with inclusion method was performed through median sternotomy with left pleurotomy. One month after operation, CT scan showed thrombus occupied between the graft and the aneurysm, and two years postoperatively, the aneurysm shrunk almost to normal size of the aorta. Therefore, our surgical procedure was considered to be proper. PMID- 1634834 TI - [Spontaneous intercostal lung hernia]. AB - A 70-year-old man admitted our clinic because of a painful bulge in the left chest wall that had appeared following a bout of coughing. CT confirmed the presence of lung herniation at the left eight interspace. At surgery a 3 x 16 cm anterolateral defect in the site was confirmed. A patch of Gore-Tex (expanded polytetrafluoroethylene) was fashioned and sewn into the defect with interrupted 3-0 Ethibond sutures. Spontaneous intercostal lung hernia is a rare lesion of thoracic wall and have not been reported in Japan. We describe a case with some reviewing. PMID- 1634836 TI - [Cell kinetics in two cases of meningioma with ultra-late pulmonary metastases]. AB - In order to elucidate the influence of surgical intervention on cell kinetics, we investigated the DNA ploidy pattern and mitotic index in two patients with metastatic pulmonary meningioma more than 10 years after the first operation for primary brain lesions. The first patient, with hemangiopericytomatous meningioma, showed a diploid pattern in all resected specimens and intrathoracic metastases obtained at autopsy, and also showed a constant mitotic indices throughout the clinical course. The second patient, with meningothelial meningioma, also showed a diploid pattern and constant mitotic indices throughout the clinical course. There was no difference in the two parameters between this second patient and 5 non-metastatic control cases. In conclusion, there was no positive correlation between these two parameters and the acceleration of tumor growth detected at every surgical intervention. PMID- 1634835 TI - [Experimental and clinical study of cardiopulmonary hemodynamics under one-lung ventilation during transthoracic esophagectomy]. AB - Cardiopulmonary hemodynamics in pre- and postoperative period after transthoracic esophagectomy under one-lung ventilation (OLV) was investigated in experimental and clinical studies. In experimental study, 30 mongrel dogs were assigned to one of the groups: Group 1 (n = 10): 2 hour right thoracotomy alone under one (n = 5) or two-lung ventilation (TLV) (n = 5), Group 2 (n = 10): thoracotomy + esophagectomy, Group 3 (n = 10): esophagectomy + right thoracic vagotomy. For further evaluation of the effect of vagotomy on increase of extravascular lung water (EVLW) on 3rd POD, the following 2 groups were designed as Group 4-1) (n = 5): thoracotomy + right thoracic vagotomy and Group 4-3) (n = 5): esophagectomy + left thoracic vagotomy. In clinical study, 30 patients underwent transthoracic esophagectomy were randomly divided into either OLV or TLV group. Cardiopulmonary hemodynamics and postoperative complications were investigated in pre- and up to 3 POD. 1. Cardiopulmonary parameters and EVLW except PaO2 and shunt ratio were not different between OLV and TLW groups in experimental study. PaO2 of OLV group dropped from the pre-thoracotomy value of 577 +/- 75 mmHg to 98 +/- 47 mmHg. This decrease was significant in comparison with TLV (582 +/- 85 mmHg to 215 +/- 132 mmHg) (p less than 0.05). Shunt ratio increased in the OLV group from 10 +/- 11% to 37 +/- 13%. This increase was also significant in comparison with TLV (24 +/- 10% from 9 +/- 9%) (p less than 0.05). However, both PaO2 and shunt ratio returned to the pre-thoracotomy value after stopping of OLV and showed no difference compared with TLV. 2. EVLW per kg was not different between 5 groups. Values of right to left lung ratio of EVLW in Group 3 and Group 4-3), 1.77 +/- 0.26 and 1.82 +/- 0.26, were greater than that in Group 1, 1.39 +/- 0.17 (p less than 0.05). This difference seems to be caused by increase of permeability of pulmonary capillaries. 3. Cardiopulmonary parameters and postoperative complications were not different between OLV and TLV groups in clinical study. In conclusion, OLV is a desirable procedure, not only for good exposure of the operative filed, but also for its safety regarding the cardiopulmonary hemodynamics. Transthoracic esophagectomy plus vagal branch denervation, which is necessary for aggressive lymphadenectomy around the trachea, increases EVLW and subsequent pulmonary edema compared with thoracotomy alone. PMID- 1634837 TI - [Modified technique for chronic tricuspid regurgitation in rabbits and evaluation of intestinal malabsorption in the chronic stage of this model]. AB - One of pathophysiological processes in cardiac cachexia with severe congestive cardiac failure is malabsorption in the intestine. This malabsorption might be caused by high venous pressure in the intestine, following congestive liver due to congestive cardiac failure. However, this has not been proved experimentally yet. In this experiment, rabbits were utilized because their body weights are relatively equal and their life cycle is shorter than that of dogs, for which experimental procedure has been established. Our purpose was first, to establish the technique which can produce tricuspid regurgitation (TR) in rabbits, and secondly, to examine the degree of malabsorption in these animals in the chronic stage of TR. SURGICAL TECHNIQUE: The TR rabbits (n = 4) were provided by means of division of the chordae of the tricuspid valve through the 4th intercostal space in the right thoracotomy. Division of the chordae was performed through the right atrial incision under direct vision while employing total temporary inflow occlusion. The duration of inflow occlusion varied from one to two minutes. RESULT: The mean of the peak right atrial pressure before the procedure was 6.5 mmHg, that just after the procedure was 16.1 mmHg, and that two to four months after the procedure was 17.0 mmHg. The peak right atrial pressure just after the procedure were higher than those before the procedure, and the peak right atrial pressure two to four months after the procedure were also higher than those before the procedure in all rabbits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634838 TI - [Hematologic and endocrinologic effects of pulsatile cardiopulmonary bypass using a centrifugal pump]. AB - The effects of pulsatile and nonpulsatile flow during cardiopulmonary bypass (CPB) with of centrifugal pump (Sarns) and membrane oxygenator, on blood cells, hemodynamics, and hormonal response were studied. In the pulsatile group (group P) in which pulsatile flow was generated by centrifugal pump and a 20 Fr arterial cannula was used, hemolysis and reduction of platelet count during CPB were more marked than in the nonpulsatile group (group NP), in which the same type of circuit was used. When the 20 Fr arterial cannula was replaced with a 24 Fr cannula (group Pc), the rate of hemolysis during CPB was significantly reduced compared with that in group P (p less than 0.05). The rate of rise in plasma free hemoglobin from 10 to 70 minutes CPB in group Pc was 15.0 mg/dl/hr, this value did not exceed that in either group NP or in group Pr, in which a roller pump rather than centrifugal pump was used to generate pulsatile flow. These findings show that pulsatile CPB with a centrifugal pump produces no deleterious hematologic effect in clinical use. The rise in the level of angiotensin II in group P was significantly smaller than that in group NP (p less than 0.05), and the rise in plasma renin activity and levels of angiotensin I, adrenalin and noradrenaline were smaller than those in group NP, although these differences were no significance. These findings indicate that the centrifugal pump generates pulsatile flow effectively, although not so effectively as to prevent the rise in peripheral vascular resistance. During CPB, there was no change in levels of thyroid hormones, including free T3, free T4 and reverse T3, in either pulsatile groups P and Pc or nonpulsatile group. TSH level in group Pc was significantly elevated in contrast with that in the nonpulsatile group (p less than 0.05), in which no change in TSH level was seen. It is suggested that pulsatile perfusion using a centrifugal pump might maintain sufficient hypothalamic-pituitary function to permit secretion of TSH in response to various stimuli. PMID- 1634839 TI - [Preservation of the heart with University of Wisconsin solution--hemodynamic and morphological evaluation in a canine heterotopically transplanted heart]. AB - University of Wisconsin (UW) solution has been reported to extend the safe cold ischemic time in the preservation of the liver, kidney and pancreas. However, there have been few reports of safe cold ischemic time in heart preservation with UW solution. The purpose of this study was to find whether UW solution can extend the safe cold ischemic time in cardiac transplantation in dogs. Heterotopic cardiac transplantation was performed in mongrel dogs after cold ischemic preservation of the hearts with UW solution, ischemic time 8, 16 and 24 hours (Gr.UW8, Gr.UW16 and Gr.UW24, respectively) and with GIK solution, ischemic time 4 hours (Gr.G4) which is considered the safe cold ischemic time in clinical cardiac transplantation. The following was studied: 1) Emax of the LV, myocardial contraction, by pressure-volume curve with the volume measured conductance catheter method, 2) myocardial tissue blood flow of the LV (MTBF), with laser doppler tissue flow meter, 3) serum CPK and electron microscopical evaluation. Emax and MTBF were measured before transplantation and after reperfusion. Their results were expressed as percentage of the values before transplantation. As results, after 120 minutes from reperfusion, Emax was recovered to 94 +/- 13% in Gr.G4, 104 +/- 11% in Gr.UW8, 67 +/- 22% in Gr.UW16 and 66 +/- 16% in Gr.UW24. Emax in Gr.G4 and Gr.UW8 were significantly (p less than 0.01) higher than that in Gr.UW16 and Gr.UW24. After 120 minutes from reperfusion, MTBF was recovered to 90 +/- 19% in Gr.G4, 98 +/- 9% in Gr.UW8, 63 +/- 19% in Gr.UW16 and 61 +/- 6% in Gr.UW24.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634840 TI - [Simple hypothermic retrograde cerebral perfusion for brain protection during aortic arch surgery]. AB - We have recently found that retrograde cerebral perfusion can be performed by simply elevating central venous pressure to 15 mmHg in the Trendelenburg position when the aortic arch is open during aortic arch surgery. During deep hypothermic (15 degrees C) perfusion of the lower half of the body with the descending aorta occluded, and with single cannulation of the right atrium for drainage, oxygen saturated venous blood perfuses the brain retrogradely, supplying it with oxygen. This method renders clamping of the aortic arch and the arch vessels unnecessary. Eleven cases of aortic arch aneurysm (9 males, 2 females; 5 true aneurysms, 5 dissecting aneurysms, one combined aneurysm; mean age, 63 years) were operated using this technique, whose clinical significance was then evaluated. Median sternotomy was performed in 4 cases, left thoracotomy in 7. Patch replacement was performed in 2 cases and graft replacement in 9 cases (the proximal arch in 2, the whole arch in 2, the distal arch in 5). In two cases coronary artery bypass surgery using the internal thoracic artery was performed simultaneously via lateral thoracotomy. Operation time was 517 +/- 139 min, pump time was 211 +/- 34 min, cardiac arrest time was 84 +/- 34 min and the lowest rectal temperature was 15.7 +/- 1.1 degrees C. In the venous return, PO2 was 188 +/- 136 mmHg, and SO2 97.5 +/- 2.9%, the respective values in the retrogradely perfused blood in the aortic arch being 46 +/- 12 mmHg and 68.8 +/- 18.8%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634841 TI - [Surgical treatment of lung cancer with mediastinoscopic positive lymph nodes]. AB - There are no definite criteria for the indication of surgery in lung cancer with mediastinal lymph node involvement. During the past 20 years, 100 patients (76 patients with adenocarcinoma and 24 patients with squamous cell carcinoma) have undergone thoracotomy for lung cancer with mediastinoscopic positive lymph nodes at our hospital. Of these, relatively curative resection was performed on 13 patients. The 5-year survival rate in these 13 patients was 28%, which was significantly higher than the 0% in 42 patients with relatively non-curative resection and the 0% in 26 patients with absolutely non-curative resection. The 5 year survival rate was 9% in both T1 (n = 14) patients and T2 (n = 37) patients. No T3 (n = 21) and T4 (n = 9) patients survived 3 years. The 5 year survival rate in patients with squamous cell carcinoma was 12% and that in patients with adenocarcinoma was 0%, but there was no significant difference. The survival rates of T1 and T2 patients were significantly higher than that of T3 patients (p less than 0.02 and p less than 0.005) respectively. Contralateral mediastinal lymph node metastasis (N3) was observed significantly more frequently in patients with adenocarcinoma (38%) than in those with squamous cell carcinoma (13%), but there was no significant difference in the survival rate. In N2 patients, the survival rate was compared between those with mediastinal nodal involvement of an early stage (N2-1) and those with lymph node metastasis of more advanced stage (N2-2) according to the lobe bearing the primary cancer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634842 TI - [Endoscopic ultrasonography for preoperative diagnosis of the hilar and mediastinal lymph node metastases in lung cancer]. AB - Fifty patients with lung cancer underwent transesophageal endoscopic ultrasonography (EUS) for preoperative detection of metastases to the hilar and mediastinal lymph nodes. An electronic ultrasonic fiberscope with a linear array (EPB-503-FS, Machida-Toshiba) was used. Later, in surgery, a total of 513 nodes that could have been detected by EUS were removed. Of these, 54 nodes were found to be metastatic histologically, and 459 were non-metastatic. The rate of detection by EUS was 65% (35/54) for the metastatic nodes; the rate was 41% (186/459) for the non-metastatic nodes (p less than 0.01). Metastatic nodes were detected at high rates in every lymph node site. Non-metastatic nodes were detected at low rates in sites 1, 2, and 4, and at the highest rate in site 7. Metastatic nodes had characteristic internal echoes, affected by the extent of tumor and necrosis present in a node, and were detected more easily than non metastatic nodes. For larger or rounder nodes, metastasis was more common (p less than 0.01). Lymph nodes that could be detected were classified into six types by their internal echo patterns; three of these types were rarely metastatic, and were called 'negative'; the other three were often metastatic, and were called 'positive'. In histological examinations, of the 'negative' nodes found in fact to be metastatic histologically, invasion by the tumor tended to be diffuse and necrosis was minute. The 'positive' nodes that were in fact metastatic tended to have one of two internal echo patterns (depending on the amount of necrosis) when invasion was diffuse, and a third pattern when invasion was localized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634843 TI - [Effect of aortic valve replacement on left ventricular function in adult patients with aortic stenosis]. AB - Echocardiographic and hemodynamic studies were obtained in 16 consecutive adult patients who underwent aortic valve replacement (AVR) with St. Jude Medical valve for aortic stenosis (AS). Three cases of congenital AS was included and two of them had undergone aortic valvotomy in childhood. One of 16 patients died due to late cardiac tamponade six weeks after AVR. Postoperative studies showed improved left ventricular (LV) functions. LV end diastolic and end systolic diameter (LVDs and LVDs) fell from 50.3 and 38.2 to 44.6 and 31.6 mm respectively (p less than 0.05). Fractional shortening (%FS) rose from 26.5 to 32.2% (p less than 0.05). End systolic wall stress (ESWS) fell from 126.2 to 69.6 k dynes/cm2 (p less than 0.01). Cardiac index and pulmonary arterial wedge pressure improved from 3.4 and 14.4 to 3.6 l/min/m2 and 10.5 mmHg respectively (ns). Preoperatively, six were functional class II, eight were class III and one was class IV (New York Heart Association classification). Postoperative improvement was as follows, eight: class I, seven: class II. In four cases, preoperative echocardiography revealed most depressed LV function in %FS (smaller than 21%) and ESWS (greater than 140). Postoperatively they improved from 18.3 and 164 to 26.0% and 72.8 k dynes/cm2 respectively. These results suggested that depressed LV function in the patients with longstanding AS was largely related to limited preload reserve due to LV enlargement and mechanical unloading of LV (correction of afterload mismatch) resulted in improvement of LV function. In conclusion, LV dysfunction owing to AS alone is reversible and AVR results in great clinical improvement. PMID- 1634844 TI - [The effects of osmolarity in reperfusion solution upon myocardial protection]. AB - The effects of several different osmolarity in reperfusion solution were studied. Experimental time course was as follows: 20 min working perfusion, 3 min cardioplegic infusion with St. Thomas Cardioplegic Solution (STS) followed by global ischemia for 33 min at 37.5 degrees C, 15 min early Langendorff reperfusion with different osmolarity by adding sucrose and 5 min late reperfusion with Krebs Henseleit bicarbonate buffer, followed by 20 min working perfusion. Percent recoveries of aortic flow showed that 290 mOsm/L in reperfusion solution possessed optimal protective properties with bell shaped dose response characteristics. PMID- 1634845 TI - [Intralobal sequestration in children--a new concept from the form of bronchial tree in sequestrated lung]. AB - Twenty cases of the intralobal sequestration of the lung in children have been experienced. The age of the patients were from eleven days to fifteen years. Intralobal sequestration was classified into two groups, (central type and peripheral type) by the way of reconstruction of the bronchial tree in the sequestrated lung. In 8 cases of central type, the site of lesion was variable. The bronchial trees of the sequestrated lung were running toward the hilus of the normal lung but the bronchi of the affected area in the normal lung were absent. The aberrant arteries were muscular in histology, and the drainage veins were pulmonary vein. In 12 cases of peripheral type, the lesion was in segment 10 area in every cases. The bronchial trees of the sequestrated lung were running toward the pulmonary ligament where an aberrant artery came from, and B10 of the normal lung were patent. The aberrant arteries were elastic in histology, and the drainage veins were pulmonary and/or azygos vein. It is conceivable that the peripheral type is the real intralobal sequestration and the central type is the mixture of some other diseases. PMID- 1634846 TI - [A useful method for the surgical treatment of active infective endocarditis--a case report using the Teflon felt reinforcing method]. AB - In the surgical treatment for active infective endocarditis (IE), perivalvular leakage is the most severe complication. We had a 42-year-old man who had active IE and a giant vegetation in the aortic valve, and a small mycotic aneurysm in the left ventricular outflow tract. Other operative observations included slight redness and a decrease in the reflex of the annular endocardium. We made a patch closure of the mycotic aneurysm, and aortic valve replacement using the Teflon felt reinforcing method. In the postoperative course, he had a pacemaker implantation with complete AV block. Postoperative pathological examination revealed inflammatory cells and plasma infiltration, and edematous change of the interstitial tissue around the cusp surface and annular side of the resected valve. These pathological changes could explain the redness and the decrease in the reflex of the annular endocardium. The edematous changes of the annular tissue might be the cause of postoperative perivalvular leakage. Reinforcement of the prosthetic valve with Teflon felt might be a useful method to prevent perivalvular leakage. There is, however, the possibility of acceleration or elongation of infective endocarditis. In our experiences of the surgical treatment for active IE, we performed valve replacement using Teflon felt in 6 patients, and not using in 27 patients. The mean period until CRP had been normalized was no significant difference between both groups (mean days using Teflon felt were 63.5 days, and not using were 75 days).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634847 TI - [A case of a small thymoma associated with myasthenia gravis in which the tumor was reduced by corticosteroid therapy]. AB - The case in this study was a 34-year-old male with a small thymoma associated with myasthenia gravis. The patient had been treated with corticosteroids for 10 months against myasthenia gravis. During the course of the treatment a chest CT revealed that the tumor had reduced. Thereafter the extended thymectomy was performed. A close examination of the excised thymus revealed the presence of a flat cystic tumor measuring 1.5 x 0.8 x 0.5 cm at the site corresponding to the CT image. This tumor was histologically ascertained to be a thymoma. The thymoma is sensitive to corticosteroids, which can effectively reduce it. As conclusion, it is necessary to check thoroughly on the presence of thymoma prior to the initiation of corticosteroid therapy to treat myasthenia gravis. PMID- 1634848 TI - [A case report of so-called solitary fibrous tumor of the mediastinum]. AB - A 52-year-old house wife was admitted to our hospital with the diagnosis of a impending rupture of the aneurysm of the ascending aorta. Chest X-ray showed an anterosuperior mediastinal mass which extended into right hemithorax and space between ascending aorta and superior vena cava on CT and MRI. Median sternotomy showed a large mass, arising from the left lobe of the thymus covered with mediastinal pleura and projecting into the right pleural cavity with no dissemination. The tumor was excised with the thymic glands together with the involved ascending aorta and pericardium. It was encapsulated tumor, 10 x 9 x 8 cm in size, 420 g in weight, and revealed central necrosis with bleeding on the cut surface. The pathological findings showed spindle cell tumor with high mitotic activity, immunoreactivity for vimentin, but not for keratin, and no ultrastructural evidence of micro villi. So far as the Japanese literature about the so-called solitary fibrous tumor of the mediastinum is concerned, this is considered to be the first case in our country. PMID- 1634849 TI - [A modified technique in total cavopulmonary connection]. AB - We have used an alternative technique in Total Cavopulmonary Connection without using any prosthetic material. The technique is a modification of Senning operation in which a flap of right atrial wall is used to create a tunnel between inferior vena cava and superior vena cava. We used this modified technique in two cases, and they showed excellent postoperative convalescence. PMID- 1634850 TI - [A case of infective endocarditis of the tricuspid valve repaired by vegetectomy and annuloplasty]. AB - A successful repair of infective endocarditis of the tricuspid valve in a drug abuser is reported. A 25-year-old woman with a history of drug addiction was referred to our hospital complaining of high fever despite antibiotic therapy. Blood cultures showed staphylococcal septicemia, and echocardiography revealed large vegetations attached to the tricuspid annulus and massive regurgitation of the tricuspid valve. Blood studies showed renal failure and hematological abnormalities due to septicemia and right ventricular failure. Excision of the vegetation and the posterior leaflet was performed along with annuloplasty (Kay's procedure). The patient's postoperative course was uneventful and subsequent echocardiographic examination disclosed no evidence of recurrence, and insignificant tricuspid valvular regurgitation. Local excision of vegetation and leaflet repair by annuloplasty may be performed in cases with well-circumscribed vegetation and minor leaflet damage. PMID- 1634851 TI - [The pulmonary venous obstruction following repair with absorbable sutures in total anomalous pulmonary venous drainage--a case report]. AB - A 4-month-old boy with infracardiac type of total anomalous pulmonary venous drainage (TAPVD) who underwent anastomosis between left atrium and common pulmonary vein at age of one month with absorbable suture of polydioxanone (PDS), was suffered from pulmonary venous obstruction (PVO). The ostia of pulmonary veins were stenosed severely. The histological findings showed that there were inflammatory changes and fibrosis around PDS suture. These findings suggested that PDS would cause inflammatory change of tissues around, which might be occurred following repair of TAPVD. PMID- 1634852 TI - [An unusual case of annular constrictive pericarditis--a "framed heart"]. AB - We presented a 62-year-old female with constrictive pericarditis of an unusual anatomy. A calcified constrictive band, 2-3 cm wide, ran parallel to the frontal plane, coursing circularly along the anterior aspect of the great arteries, right atrium, diaphragmatic surface of the right ventricle, posterolateral aspect of the left ventricle and back to the great arteries. The course of the constrictive band was circular but completely different from that of typical annular constrictive pericarditis in which a constrictive band runs along the atrioventricular groove. Hemodynamic consequences of our patient was rather non specific impairment of ventricular filling than functional valvular stenoses due to external compression characteristic for the typical annular constrictive pericarditis. Effective surgical relief of the constriction was accomplished under cardiopulmonary bypass and cardioplegic cardiac arrest. PMID- 1634853 TI - Evaluation of quality of lateral full spine radiographs: a statistical study. AB - OBJECTIVE: This study examines the effects of filtration on X-ray quality in 287 lateral full spine radiographs of human subjects. The impact of the subject's sex and age on the effects of filtration was also examined. DESIGN: X rays obtained with and without filtration were selected at random from various chiropractic clinics in North America. Five college instructors from various clinical backgrounds classified each film as adequate film quality, or as over- or underexposed in each of the cervical, thoracic, lumbar and sacral spinal regions. RESULTS: Log linear analyses showed that the use of filtration produced the best overall film quality, and that film quality decreased as age increased in all spinal regions, regardless of filtration usage. A higher percentage of films of subjects less than 54 yr of age were judged to be of adequate quality when filtration was used. Films of male subjects had better quality in the lower spinal regions; films of females were better in the upper regions. CONCLUSIONS: By the evidence supported by the statistical analyses, it is suggested that lateral full spine films may only be used as a means for postural screenings if filtration is always used, and to take the sex and age of the patient into account in deciding whether to change technique exposure factors or to use sectional views, which would increase the probability of better quality films. PMID- 1634854 TI - Who's interested in chiropractic history? AB - OBJECTIVE: To determine the extent of interest in chiropractic history among chiropractors in various nations, states and provinces. DATA SOURCES: The worldwide chiropractor population distribution was determined by noting the circulation of the biweekly magazine, Dynamic Chiropractic. Interest in chiropractic history among chiropractors was implied by inclusion in the Membership Directory of the Association for the History of Chiropractic (AHC). DATA EXTRACTION: An interest index was derived by expressing the number of members of the AHC as a percentage of the chiropractor population in each region. DATA SYNTHESIS: Worldwide membership in the AHC involves less than 1% of the total estimated chiropractor population; Canadian chiropractors demonstrated twice as much interest proportionately compared to all other members of the profession. CONCLUSIONS: Reasons for the minimal interest in chiropractic history are considered, and recommendations for increasing historical interest and scholarship are provided. PMID- 1634855 TI - Scapholunate failure: a long term clinical follow-up. AB - Rotary subluxation of the carpal scaphoid is a rare condition that may lead to collapse of the wrist. The subluxation is the result of disruption of the scapholunate interosseous ligament, often secondary to scaphoid fracture or significant trauma. The characteristic clinical and radiographic findings are discussed. Controversy exists regarding treatment, but lack of treatment predisposes the wrist to degenerative changes. A case report is discussed which illustrates the salient features of this condition. PMID- 1634856 TI - The fixed response objective structured clinical examinations: a useful adjunct for assessing competence in diagnostic decision making? PMID- 1634857 TI - Assessment of cervical vertigo. PMID- 1634858 TI - The superior intracapsular ligament of the sacroiliac joint: presumptive evidence for confirmation of Illi's ligament. PMID- 1634859 TI - Influence of substrate on retraction of neurites following electrical activity of leech Retzius cells in culture. AB - 1. The aim of these experiments was to determine how electrical stimulation of identified neurones in culture influences their growth on defined substrates. Single Retzius cells isolated from the central nervous system (CNS) of the leech were plated in culture dishes coated with the plant lectin Concanavalin A or with extracellular matrix extract containing leech laminin to promote neurite outgrowth. Stimuli were applied by a fine tungsten microelectrode placed close to the cell surface. The efficacy of electrical stimulation was checked occasionally by recording intracellularly with a microelectrode. 2. After the period of stimulation had ended, there was a short delay before neurones plated on leech laminin retracted their neurites. Of 112 neurones, only 11 failed to respond to stimulation. Neurite retraction in each cell was non-uniform, some processes retracting while others did not. After having retracted, most neurites subsequently showed clear regrowth. The degree of retraction depended on the duration of the stimulus train: whereas a few minutes was sufficient to produce observable effects, prolonged periods of stimulation caused more extensive retraction. Trains of impulses at 4 s-1 were equally effective when they were delivered in intermittent bursts or continuously. 3. The time in relation to growth at which stimuli were applied was of critical importance. Neurones stimulated during the phase of rapid outgrowth on leech laminin did not retract their neurites, which continued to elongate during and after stimulation. Neurones that had not retracted during the early phase were stimulated again later, when extension and outgrowth of neurites had ceased or slowed. At this stage stimulation was followed by retraction and subsequent regrowth. 4. Retzius cells plated on a substrate of Concanavalin A instead of leech laminin failed to show any retraction after stimulation. 5. To investigate the possible role of Ca2+, cells were grown with raised concentrations of Mg2+ in the bathing fluid. Raised [Mg2+] did not influence the rate or the extent of neurite outgrowth. It reduced, but did not block, the effects of electrical stimulation. Earlier experiments have shown that growth on Concanavalin A occurs without obvious Ca2+ entry following stimulation. Together with the present experiments, the results suggest that Ca2+ entry following impulses in cells grown on laminin is responsible for the massive retraction. PMID- 1634860 TI - Degenerative changes in the structure of neuromuscular junctions of Manduca sexta during metamorphosis. AB - During the degenerative processes that precede and accompany metamorphosis of the larval mesothoracic dorsal longitudinal muscles of Manduca sexta, the motor nerves and neuromuscular junctions undergo a variety of structural changes that are largely secondary to the changing morphologies of their respective glia. In the central region of the main motor nerve, the multiple layers of glial processes surrounding each of the large axons withdraw, leaving them apposed. In the peripheral region of the main motor nerve and in the secondary and tertiary nerve branches supplying the muscle, the outer glial processes of the nerve sheath and those that loosely wrap accompanying small neurosecretory axons all swell. Phagocytic cells and cells of unknown function invade the outer region of the nerve. In the neuromuscular junctions, the glial cells withdraw their processes from a complicated interdigitation with processes from the muscle fiber and from their relationship with the nerve terminal. As degeneration proceeds, this allows a greater area of contact between each nerve terminal and the muscle fiber. Within each junction there is a mixture of both functional and non functional regions and active zones, as determined by both thin-section and freeze-fracture observations. No correlation was found between the degree of degeneration of a neuromuscular junction and its association with a particular muscle fiber or its position on the fiber relative to the origin or insertion. PMID- 1634861 TI - Gas exchange, metabolite status and excess post-exercise oxygen consumption after repetitive bouts of exhaustive exercise in juvenile rainbow trout. AB - Juvenile rainbow trout (approximately 6 g) were exercised to exhaustion in two 5 min bouts given 6 h apart. Resting levels of whole-body lactate and glycogen were restored prior to the second bout. The rate of O2 consumption increased about threefold 5 min after each bout of exercise, while recovery time decreased from 4 h after the first bout to 2-3 h after the second. The excess post-exercise oxygen consumption, i.e. 'oxygen debt', was significantly reduced by 40% after the second exercise bout, despite almost identical rates of lactate clearance and glycogen resynthesis. The rates of CO2 and ammonia excretion increased sixfold and threefold, and recovery times decreased from 4-6 h to 3 h and from 3 h to 1.5 h, respectively. After the first bout, whole-body lactate levels peaked at 5 min post-exercise at about 8.5 times pre-exercise levels. After the second bout, lactate levels peaked at 0 min post-exercise and fell more rapidly during recovery. Whole-body glycogen levels decreased by 70% and 80% and ATP levels decreased by 75% and 65% after the first and second bouts, respectively, while glucose levels increased about 1.5-fold immediately after both bouts. Creatine phosphate levels decreased by 70% and 80% after the first and second bouts, respectively. After 6 h of recovery, creatine phosphate levels were higher after the second bout than after the first. These findings suggest that exhaustive exercise may cause a 'non-specific' increase in metabolic rate not directly related to the processing of metabolites, which is reduced upon a subsequent exercise bout. This is in contrast with the classical 'oxygen debt hypothesis', which states that the oxygen debt and lactate clearance are linked. Furthermore, it appears that two sequential exercise bouts are sufficient to induce a 'training effect', i.e. improved rates of metabolic recovery. PMID- 1634862 TI - The influence of cerebellar lesions on the swimming performance of the trout. AB - The influence of partial cerebellar ablation on the performance of rainbow trout, Oncorhynchus mykiss, swimming in a water tunnel was studied. Before surgery, all fish maintained a steady position in the water tunnel at all speeds tested. A linear relationship was found between the specific velocity (body length s-1) and the tail-beat frequency. After partial cerebellectomy, the fish swam well in the tunnel at low speeds, retaining the relationship between tail-beat frequency and specific velocity, but they were unable to maintain a steady position at water speeds requiring tail-beat frequencies above 3.5 s-1 and were swept backwards. Two sham-operated fish swam at all water speeds tested. Post mortem histological investigation showed that the lesions were restricted to the cerebellar corpus. We conclude that the cerebellum plays no role in the generation of motor programmes but may be essential for their selection and implementation. PMID- 1634863 TI - Cardiovascular responses of the red-blooded antarctic fishes Pagothenia bernacchii and P. borchgrevinki. AB - The aim of this study was to investigate cardiac performance and cardiovascular control in two red-blooded nototheniid species of antarctic fishes, Pagothenia bernacchii (a benthic fish) and P. borchgrevinki (a cryopelagic fish), and to make comparisons with existing information on haemoglobin-free antarctic teleosts. In quiescent P. bernacchii at 0 degrees C ventral aortic pressure (PVA) was 3.09 kPa and cardiac output (Q) was 17.6 ml min-1 kg-1, with a heart rate (fH) of 10.5 beats min-1 and stroke volume of 1.56 ml kg-1. Following atropine treatment, Q was maintained but heart rate increased and stroke volume decreased. Resting heart rate resulted from an inhibitory cholinergic tone of 80.4% and an excitatory adrenergic tone of 27.5%. The intrinsic heart rate was 21.7 beats min 1 at 0 degrees C. In quiescent P. borchgrevinki at 0 degrees C, PVA was 3.6 kPa, Q was 29.6 ml min-1 kg-1 and stroke volume was 2.16 ml kg-1. The resting heart rate in P. borchgrevinki of 11.3 beats min-1 resulted from an inhibitory cholinergic tone of 54.5% and an excitatory adrenergic tone of 3.2%. The intrinsic heart rate was 23.3 beats min-1. P. bernacchii maintained Q during a progressive decrease in water oxygen tension from 20 to 6.7 kPa, but fH was increased significantly. Thus, although there is cholinergic control of the heart, no hypoxic bradycardia was observed. Recovery from hypoxia was associated with increases in Q and fH; stroke volume returned to control values. PVA declined in recovery as total vascular resistance decreased. Hypoxic exposure following atropine treatment resulted in progressive increases in PVA, Q and stroke volume; fH decreased during the recovery period. Hypoxic exposure in P. borchgrevinki produced similar cardiovascular responses to those observed in P. bernacchii. During an acute increase in water temperature from 0 to 5 degrees C, P. bernacchii regulated Q and total vascular resistance. Stroke volume decreased as fH increased. The intrinsic heart rate had a Q10 of 1.96 over this temperature range. P. bernacchii maintained chronotropic inhibition up to a temperature of 2.5-3.0 degrees C. However, by 5 degrees C this chronotropic inhibition of the heart rate was lost. Infusion of adrenaline into the ventral aorta of P. bernacchii resulted in significant increases in Q, fH, PVA and total vascular resistance. Infusion of adrenaline after atropine treatment caused similar cardiovascular changes without the change in fH. P. borchgrevinki could sustain swimming in a water tunnel at approximately 1 body length per second for 6-10 min.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1634864 TI - Responses to freezing exposure of hatchling turtles Trachemys scripta elegans: factors influencing the development of freeze tolerance by reptiles. AB - Hatchling red-eared turtles Trachemys (= Pseudemys) scripta elegans (Wied) from a Louisiana population display a significant ability to withstand the freezing of extracellular body fluids. All animals survived at least 2 h of freezing at -2.5 or -4 degrees C. At -2.5 degrees C, survival declined to 50% after 6 h of freezing and no animals recovered after 24 h or longer, when mean ice content reached 54.7 +/- 1.4% of total body water. At -4 degrees C, all turtles recovered from 4 h of freezing exposure with a mean ice content of 49.6 +/- 2.4%, but survival dropped sharply thereafter with no animals recovering after 8 h, when ice content had reached 64.5 +/- 0.7%. Survival times were substantially shorter and percentage ice values greater than comparable values for hatchling painted turtles (Chrysemys picta (Schneider)) from northern populations subjected to identical freezing exposures. The ability to synthesize cryoprotectants in response to freezing was poorly developed in T. s. elegans; maximal accumulation of glucose was only 3.2 mumol g-1 wet mass in liver. Lactate content increased two- to threefold in oxygen-sensitive organs (heart and brain) during freezing, but levels of lactate and other putative cryoprotectants were unchanged in other organs. Total free amino acid content rose significantly in liver, muscle and blood during freezing; increased taurine concentration was primarily responsible for the changes in liver and blood. The capacity for freezing survival by T. s. elegans hatchlings from southern populations would be of limited use for hibernation in a cold climate, but the metabolic responses to freezing displayed by these animals might be enhanced by northern populations to increase their freeze tolerance. PMID- 1634865 TI - Calcium transients in identified leech glial cells in situ evoked by high potassium concentrations and 5-hydroxytryptamine. AB - We have recorded the fluorescence of Fura-2-loaded, identified glial cells in the neuropile of the central nervous system of the leech Hirudo medicinalis using the ratio of emission at 350 nm excitation to that at 380 nm excitation as an indicator of intracellular Ca2+ concentration ([Ca2+]i). The neuropile glial cells were exposed by mechanically removing the overlying ganglionic capsule and the neuronal cell bodies and were then impaled using a microelectrode under visual control to inject Fura-2 ionophoretically. The resting Ca2+ level was measured using digitonin or Triton to permeabilize the cell membrane at different external concentrations of Ca2+; it was found to vary between 5 and 79 nmol l-1 and averaged 32 +/- 23 nmol l-1 (+/- S.D., N = 7). Raising the external K+ concentration from 4 to 20 mmol l-1 or adding 50 mumol l-1 5-hydroxytryptamine (5 HT) produced a rapid, reversible rise in [Ca2+]i. During prolonged exposure to high [K+] or 5-HT, [Ca2+]i remained high. Upon restoring normal external [K+] or removing 5-HT, [Ca2+]i returned to its initial resting value within 1-2 min. The responses of [Ca2+]i to high [K+] and 5-HT were greatly reduced in nominally Ca(2+)-free saline, suggesting that the [Ca2+]i transients required an influx of Ca2+ into the cells. In the presence of 5-HT, the rise in [Ca2+]i was accompanied by a decrease in the resistance and an increase in the responsiveness to K+ of the glial cell membrane, indicating the existence of a Ca(2+)-dependent K+ conductance elicited by 5-HT. PMID- 1634866 TI - The influence of temperature on ryanodine sensitivity and the force-frequency relationship in the myocardium of rainbow trout. AB - The relationship between stimulation frequency and contraction was established for ventricular strips from rainbow trout heart at 5, 15 and 25 degrees C. Compared to mammalian species, changes in temperature had little impact on force development in trout ventricle at physiologically relevant stimulation frequencies. However, the force-frequency relationship was changed from a biphasic response with a minimum around 0.2 Hz at 5 and 15 degrees C to a monophasic decline in force with increasing frequency at 25 degrees C. Ryanodine reversed the negative force-frequency relationship at 25 degrees C. Potentiation of twitch force after a 5 min rest period was increased from 121 +/- 4% at 15 degrees C to 209 +/- 12% at 25 degrees C. A similar augmentation was seen for the maximal rate of force development. Rest potentiation of both force and maximal rate of force development (dF/dT) was abolished by ryanodine at both 15 and 25 degrees C. The ryanodine concentration causing a half-maximal reduction in rest potentiation of force was 51 nmol l-1 at 25 degrees C and 483 nmol l-1 at 15 degrees C. Rest potentiation was maximally reduced by 10 mumol l-1 ryanodine to 50 and 79% of the value in the absence of ryanodine at 25 and 15 degrees C, respectively. At 5 degrees C, rest potentiation was similar to that at 15 degrees C. At 5 degrees C, there was no rest potentiation of dF/dT and ryanodine did not reduce rest potentiation of force. Instead, rest potentiation was correlated with a potentiation of time to peak tension (TPT) at 5 degrees C. Thus, in trout ventricle, force correlates with TPT at 5 degrees C and seems to be regulated by a ryanodine-insensitive mechanism, while at 25 degrees C force is correlated with the maximal rate of force development and the sarcoplasmic reticulum appears to contribute significantly to excitation-contraction coupling. PMID- 1634867 TI - Degenerative changes in the muscle fibers of Manduca sexta during metamorphosis. AB - The ultrastructural changes associated with the early stages of degeneration of the larval mesothoracic muscle fibers of Manduca sexta were examined during the prepupal period and on the first day after ecdysis. Over this 5 day period, the muscle fibers decrease in cross-sectional area but increase in apparent surface area compared to the dimensions of early fifth-instar fibers. Large numbers of electron-dense granules or droplets are formed and extruded from the muscle cytoplasm into the hemolymph; this process may account for some of the decrease in muscle fiber mass and may represent a developmental mechanism for recycling nutrients. As the fibers shrink, the thick basal lamina is thrown into folds. Phagocytic hemocytes (granulocytes) congregate in clusters over the surface of the degenerating fibers and appear to remove specifically the basal lamina. The timely removal of the thick larval basal lamina may be essential for subsequent fusion of myoblasts to the residual larval myofibers. The contractile elements within the degenerating muscle fibers become disorganized but are not dysfunctional at the end of the first 12 h after the pupal ecdysis. Tracheoles withdraw from intimate contact with each muscle fiber in its clefts and T-tubules and associate in groups adjacent to it. Mitochondria appear to be degenerating. These structural changes are concurrent with a previously observed decline in resting potential and suggest that a significant change in the electrical properties of the muscle fibers should be expected as well. PMID- 1634868 TI - Nucleocapsid gene sequence of a North American isolate of viral haemorrhagic septicaemia virus, a fish rhabdovirus. AB - Viral haemorrhagic septicaemia is the most important viral disease of trout in Europe. The causative agent, viral haemorrhagic septicaemia virus (VHSV), a member of the lyssavirus genus of the rhabdoviridae family, was formerly believed to be confined to portions of the European continent; however in 1988, VHSV was isolated from adult chinook (Oncorhynchus tshawytscha) and coho (O. kisutch) salmon returning to two hatcheries in the northwestern part of the State of Washington, U.S.A. Initial fears were that the virus had been imported into North America, perhaps by aquaculture activities. The nucleotide and deduced amino acid sequences of the nucleocapsid (N) gene of one of the North American (Makah) isolates of VHSV were determined and compared with published sequences of a European reference strain of VHSV (07-71) and the Round Butte strain of infectious haematopoietic necrosis virus (IHNV), another salmonid fish rhabdovirus that is enzootic in western North America. The N gene of the Makah isolate of VHSV shared a similarity of 88.433% at the nucleotide level and 94.802% at the amino acid level with the N gene of the European strain of VHSV, and 62.121% amino acid similarity with the N protein of IHNV. Like the European reference isolate, the North American isolate of VHSV showed three domains in the N protein, the central one being the most conserved and the likely site of interaction with genomic RNA. This was also the region of highest similarity with the amino acid sequence of IHNV. The sequence data suggested that the Makah and 07-71 isolates were of independent origin. PMID- 1634869 TI - Characterization of a new picorna-like virus, himetobi P virus, in planthoppers. AB - Picorna-like virus particles, 29 nm in diameter, were purified from apparently healthy Laodelphax striatellus Fallen. The virus particles had a buoyant density of 1.352 g/ml in CsCl and a sedimentation coefficient of 161 s. The virus capsid proteins consisted of three major polypeptides of M(r)s 36,500, 33,000 and 28,000, and three minor polypeptides. The virus contained a major ssRNA of M(r) 2.8 x 10(6) and was also frequently associated with a minor dsRNA of M(r) 4 x 10(6). The 3' end of the ssRNA had a poly(A) tract of about 60 adenine residues. The virus has been provisionally named himetobi P virus. PMID- 1634870 TI - Baculovirus structural proteins. PMID- 1634871 TI - Electrotransfection of protoplasts from tomato, wild tomato, barley and chrysanthemum with tobacco mosaic virus RNA. AB - Protoplasts isolated from tomato, wild tomato, barley and chrysanthemum were electrotransfected with tobacco mosaic virus (TMV) RNA under almost the same optimum electric conditions: five square DC pulses of 50 microseconds duration at 500 to 800 V/cm, with the protoplasts suspended at 2 x 10(5)/ml in 0.5 M-mannitol containing 100 microM-MgCl2 and 10 to 20 micrograms/ml TMV RNA. ELISAs of these transfected protoplasts showed that the yields and the growth curves of the virus were quite similar, indicating a lack of host specificity in the initially infected cells of these plants. PMID- 1634872 TI - Analysis of the dsRNAs of apple chlorotic leaf spot virus. AB - Double-stranded RNAs were isolated from plants infected with five different isolates of apple chlorotic leaf spot virus (ACLSV). Analysis by PAGE and by Northern blot hybridization showed that six major species of viral dsRNA of approximately 7.5, 6.4, 5.4, 2.2, 1.1 and 1.0 kbp can be detected in infected plants, irrespective of the ACLSV isolate used. In addition to the dsRNA of 7.5 kbp corresponding to the full-length genome, the size and position on the genome of the 2.2 and 1.1 kbp species indicate that these are very probably double stranded forms of subgenomic RNAs allowing the expression of the internal open reading frames coding respectively for the ACLSV 50K and coat proteins. The subgenomic messenger for the coat protein was indeed detected in total RNA preparations from infected plants. Surprisingly, the two most abundant dsRNA species, of 6.4 and 5.4 kbp, were found to be 5'-coterminal with the genomic RNA. A model for the expression of the genome of ACLSV and for the production of the molecules 5'-coterminal with the genomic RNA is presented. PMID- 1634873 TI - Autocatalytic activity of the tobacco etch virus NIa proteinase in viral and foreign protein sequences. AB - The small nuclear inclusion (NIa) protein of the tobacco etch virus (TEV) is synthesized initially as part of a genome-derived high M(r) precursor. The NIa protein releases itself from this genome-derived precursor by self-cleavage, or an autocatalytic processing event. Cleavage between specific glutamine-glycine dipeptides at the N and C termini generates the 430 amino acid or 49,000 M(r) (49K) NIa protein. The requirements of this autocatalytic release, or cis cleavage, were examined by constructing gene cassettes encoding the TEV NIa protein which could be ligated into particular locations in cDNA of the TEV genome and also into foreign gene DNA sequences. Using cell-free transcription and translation systems, polyproteins containing TEV NIa sequences were synthesized and assayed for (i) autocatalysis and (ii) the ability of a functional NIa proteinase, purified from plant tissue, to cleave in bimolecular or trans reactions various artificial polyproteins which contained an inactive form of the NIa proteinase. The NIa self-cleavage events required an active proteinase sequence and a consensus TEV cleavage site sequence at the N and C termini. These results were consistent for NIa protein sequences placed at a foreign TEV cleavage site or in unrelated proteins. Differences were noted in the trans cleavage of these sites. PMID- 1634874 TI - Conserved terminal sequences of rice ragged stunt virus genomic RNA. AB - The 5'- and 3'-terminal nucleotide sequences of the dsRNA genome segments of rice ragged stunt virus (RRSV), a member of the plant Reoviridae, were determined and compared with those published for other viruses in this family. The 5'- and 3' terminal regions of the RRSV plus strand RNA from all genome segments were found to have the same conserved hexanucleotide (5' GAUAAA---) and tetranucleotide (-- GUGC 3') sequences, respectively. These conserved terminal sequences were different from those found in viruses in the Phytoreovirus and Fijivirus genera. This result confirms that, as already suggested, RRSV should be placed in a third genus. PMID- 1634875 TI - Secretion of fowl plague virus haemagglutinin from insect cells requires elimination of both hydrophobic domains. AB - In the present study we have investigated the role of the hydrophobic domains of the fowl plague virus (FPV) haemagglutinin (HA) on its intracellular transport and maturation in insect cells. To this end processing of full-length HA (A+) has been compared to that of two truncated forms lacking either the cytoplasmic domain and the transmembrane domain (A-) or lacking the entire HA2 subunit, i.e. the transmembrane domain and the fusion peptide (HA2-). All glycosylation sites present on A- and HA2- were glycosylated, indicating that both truncated forms were completely translocated in the endoplasmic reticulum. Unlike A+, A- and HA2- did not form trimers as indicated by cross-linking, gradient centrifugation and studies employing conformation-specific antibodies. Whereas HA2- was efficiently secreted, A- was retained in the cells in an apparently membrane-bound form. The data show that the carboxy-terminal transmembrane region is essential for the formation and stability of the trimers of the FPV HA. These observations also indicate that, under certain conditions, the fusion peptide of the FPV HA can serve as a membrane anchor. PMID- 1634876 TI - Oligomerization and post-translational processing of glycoprotein G of human respiratory syncytial virus: altered O-glycosylation in the presence of brefeldin A. AB - The post-translational maturation of the attachment G glycoprotein of human respiratory syncytial virus (RSV) was investigated. The G protein formed homo oligomers which sedimented in sucrose gradients at the same rate as the fusion F protein tetramer. Oligomerization of the G protein was insensitive to carbonylcyanide m-chlorophenylhydrazine, showing that this step occurs in the endoplasmic reticulum prior to O-glycosylation which initiated in the trans-Golgi compartment. The sedimentation of the G protein oligomer was essentially unchanged by the subsequent addition of O-linked sugars. This indicated that their contribution to the M(r) of the G protein is less than that estimated by electrophoretic mobility. It also suggested that O-glycosylation is not an important determinant of G protein oligomerization and, by implication, of polypeptide folding. The G protein is palmitylated. In short labelling pulses, the G protein accumulated as two species of 48K and 50K which contained only N linked sugars, whose difference in M(r) was due solely to an N-linked sugar, which both assembled into oligomers, but which differed in the rate of subsequent O-glycosylation. The G protein was not detectably O-glycosylated in the presence of monensin, confirming previous work. In the presence of brefeldin A (BFA), it accumulated as a partially O-glycosylated species (BFA-G) of 68K to 78K. But further analysis by chase incubations following BFA-washout, by lectin-binding, and by glycosidase treatment suggested that BFA-G was not a fully authentic processing intermediate. In particular, some of the O-linked side-chains of the BFA-G protein were found to be sialylated. Rather than being a normal step in processing, this sialylation probably was due to altered distribution or activity of sialyltransferases during BFA treatment and may have resulted in the premature termination of elongation of some of the O-linked side-chains. Thus, these studies (i) indicate that O-glycosylation of the G protein begins in the trans Golgi compartment and (ii) suggest that O-glycosylation is completed in as a subsequent compartment, but this latter suggestion is complicated by the evidence that the BFA-G protein is not a fully authentic intermediate.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1634877 TI - Sequence analysis of the genes encoding the nucleocapsid protein and phosphoprotein (P) of phocid distemper virus, and editing of the P gene transcript. AB - The nucleotide and deduced amino acid sequences of two genes of phocid distemper virus (PDV) were determined by cDNA cloning and sequencing. The long open reading frame of the gene encoding the nucleocapsid (N) protein is presented. As with other morbilliviruses, the phosphoprotein (P) gene of PDV was found to be located after the 5' end of the N gene and before the 3' end of the matrix protein gene. The P gene was shown to have the capacity to encode three distinct proteins, P, V and C, in analogy to other morbilliviruses. The results presented provide evidence for editing of the PDV P mRNA transcript by insertion of G residues. When the nucleotide and deduced amino acid sequences of the N, P, V and C genes were aligned with corresponding sequences of other established members of the morbillivirus genus, compelling homology was found between PDV and canine distemper virus (CDV), whereas there was markedly less similarity between PDV and measles virus or rinderpest virus. On the basis of the alignments presented, the estimated amino acid sequence similarity between the N and P genes of PDV and CDV was 84% and 76%, respectively. These differences at the genomic level indicate that the viruses are two separate entities. PMID- 1634878 TI - Basis of neurovirulence of avirulent rabies virus variant Av01 with stereotaxic brain inoculation in mice. AB - Av01 is a variant of the challenge virus standard strain of fixed rabies virus that was selected with a neutralizing anti-glycoprotein monoclonal antibody, and has a single amino acid change in the glycoprotein. It is avirulent after both intracerebral and peripheral routes of inoculation in adult mice. In this study, Av01 was found to be neurovirulent with stereotaxic brain inoculation in either the striatum or cerebellum of adult mice. Mice that had been inoculated simultaneously with Av01 by the intracerebral and intrastriatal routes recovered. More infectious virus was present in the brains of mice inoculated intrastriatally than intracerebrally, and more neurons contained rabies virus antigen. However, the topographical distribution of infected neurons was similar with both routes. Serum neutralizing antibodies against rabies virus were produced later and in smaller quantities after intrastriatal inoculation. Av01 is probably neurovirulent after stereotaxic brain inoculation because this route produces both a direct site of viral entry into the central nervous system and a low level of immune stimulation. PMID- 1634879 TI - Lack of human immunodeficiency virus type 1 (HIV-1) replication and accumulation of viral DNA in HIV-1-infected T cells blocked in cell replication. AB - Human immunodeficiency virus type 1 (HIV-1) infection of the CD4+ SupT and CEM cell lines, blocked in cell replication by the polymerase alpha inhibitor aphidicolin (APC), was studied. The APC-treated cells showed a lack of viral production, but the presence of single cell killing. High levels of unintegrated viral DNA forms were found in the infected APC-treated cells as compared with untreated cells. Moreover, an increased rate of viral replication occurred in the remaining viable cells following removal of APC. The results indicate that HIV-1 entry and reverse transcription can take place in cells blocked in the S phase of the cell cycle. Replication of infectious progeny virions appears to require de novo cell division. Finally, accumulation of viral DNA in cells during APC treatment can result in cytopathological effects and subsequent enhancement of virus production. PMID- 1634880 TI - Recombinant interleukin 4 stimulates human immunodeficiency virus production by infected monocytes and macrophages. AB - Recombinant interleukin 4 (IL-4) stimulated extracellular (EC) and intracellular (IC) production of human immunodeficiency virus (HIV) from infected human blood derived monocytes and macrophages when incubated with the cells after but not before virus inoculation. Significant stimulation was observed in 20 of 27 experiments with monocytes (inoculated with HIV immediately after adherence) and 10 of 13 experiments with macrophages (inoculated after 5 days adherence) using a total of 30 normal donors of monocytes and macrophages, and 11 recent isolates of monocytotropic HIV strains (after one passage in mononuclear cells). Marked increases in EC and IC HIV antigen were observed in some experiments, which were comparable with the maximal stimulatory effects of other cytokines such as IL-2. IL-4 also had similar effects on infectious HIV concentration as measured by reverse transcriptase and TCID50 assays. Antibody to IL-4 prevented the stimulatory effect of the cytokine. The proportion of monocytes and macrophages infected by HIV, as determined by in situ hybridization, also increased after incubation with IL-4 for 7 days. The most marked effects were observed with HIV infected macrophages, for which the proportion of unstimulated infected cells was lower (35 to 45% increasing to 66 to 70% with IL-4 treatment). There was also an increased proportion of cells with high granule concentrations, suggesting that IL-4 increases the intracellular concentration of viral nucleic acids. This was supported by semi-quantitative hybridization experiments showing that total HIV RNA increased in IL-4-stimulated monocytes 48 to 96 h after HIV inoculation. A marked increase in aggregates was observed on day 7 in HIV-infected monocytes treated with IL-4, compared to that in HIV-infected cells alone or IL-4-treated uninfected monocytes. These findings suggest that IL-4 stimulates HIV replication in the early phases of infection and may also facilitate virus transmission by aggregate formation. PMID- 1634881 TI - Low pH deforms the influenza virus envelope. AB - Influenza virus membrane fusion is induced by low pH, which triggers an irreversible conformational change in the viral haemagglutinin (HA). The result of this change is the extrusion of the HA fusion peptide, after which it may act in the fusion of virus and endosomal membranes. Here we describe electron microscopic observations on low pH-treated virus after negative staining or cryo electron microscopy of virus in the frozen hydrated state. The results indicate a destabilization of the virus membrane at low pH that can be reversed by returning the pH to neutral. PMID- 1634882 TI - Bovine respiratory syncytial virus nucleocapsid protein: mRNA sequence analysis and expression from recombinant vaccinia virus vectors. AB - The nucleotide sequence of the mRNA encoding the nucleocapsid (N) protein of bovine respiratory syncytial (BRS) virus, strain 391-2, was determined. Recombinant vectors containing a cDNA of the complete N gene were constructed, and expression of the N protein in eukaryotic cells was demonstrated using two different vector systems. The BRS virus N mRNA was 1197 nucleotides in length, exclusive of poly(A), and had a single major open reading frame that encoded a polypeptide of 391 amino acids with a calculated M(r) of 42.6K. The nucleotide and amino acid sequences of the BRS virus N gene were compared to those of human respiratory syncytial (HRS) virus strains A2 and 18537, and to BRS virus strain A51908. The level of nucleic acid identity between the N mRNA of BRS virus 391-2 and both HRS virus subtypes was 80 to 81%, whereas the identity between the two BRS virus strains was 97%. A 93 to 94% level of identity was observed between the deduced amino acid sequences of the N protein of BRS virus 391-2 and the corresponding sequences of the two HRS virus strains. The two BRS virus N proteins differed in amino acid sequence at only three positions. Recombinant BRS virus N protein was expressed using two different vector systems: in cells from a plasmid using the vaccinia virus/T7 polymerase expression system or from a recombinant vaccinia virus. N proteins synthesized by the two vector systems migrated with an electrophoretic mobility identical to that of authentic BRS virus N protein, and were precipitated by anti-BRS virus antibodies. PMID- 1634883 TI - Castration and antisteroid treatment impair vocal learning in male zebra finches. AB - Both song behavior and its neural substrate are hormone sensitive: castrated adult male zebra finches need replacement of gonadal steroids in order to restore normal levels of song production, and sex steroids are necessary to establish male-typical neural song-control circuits during early development. This pattern of results suggests that hormones may be required for normal development of learned song behavior, but evidence that steroids are necessary for normal neural and behavioral development during song learning has been lacking. We addressed this question by attempting to eliminate the effects of gonadal steroids in juvenile male zebra finches between the time of initial song production and adulthood. Males were castrated at 20 days of age and received systemic implants of either an antiandrogen (flutamide), an antiestrogen (tamoxifen), or both drugs. The songs of both flutamide- and tamoxifen-treated birds were extremely disrupted relative to normal controls in terms of the stereotypy and acoustic quality of individual note production, as well as stereotypy of the temporal structure of the song phrase. We did not discern any differences in the pattern of behavioral disruption between birds that were treated with either flutamide, tamoxifen, or a combination of both drugs. Flutamide treatment resulted in a reduced size of two forebrain nuclei that are known to play some role unique to early phases of song learning [lateral magnocellular nucleus of the anterior neostriatum (IMAN) and area X (X)], but did not affect the size of two song control nuclei that are necessary for normal song production in adult birds [caudal nucleus of the ventral hyperstriatum (HVc) and robust nucleus of the archistriatum (RA)]. In contrast, treatment with tamoxifen did not result in any changes in the size of song-control nuclei relative to normal controls, and it blocked the effects of flutamide on the neural song-control system in birds that were treated with both drugs. Castration and antisteroid treatment exerted no deleterious effects on the quality of song behavior in adult birds, indicating that gonadal hormones are necessary for the development of normal song behavior during a sensitive period. PMID- 1634885 TI - Demonstration of motoneuron-12 sparing in cultured Manduca sexta ventral nerve cords. AB - The emergence of the adult Manduca sexta moth is accompanied by the death of half of the neurons present in the pupal abdominal nervous system (Truman, 1983). This developmental neuronal death is highly selective, so that the same neurons die at the same time relative to emergence in every moth. In the case of the MN-12 motoneurons, this cell death is regulated both by hemolymph concentrations of a steroid hormone, 20-hydroxyecdysone, and by actions exerted by adjacent ganglia (Truman and Schwartz, 1984; Fahrbach and Truman, 1987). This latter effect, which has been previously described in isolated abdomens and in moths with transected ventral nerve cords, has now been reproduced under controlled culture conditions in which the selectivity and extent of postemergence neuronal death is comparable to that seen in vivo. With respect to the MN-12 neurons found in the most anterior unfused abdominal ganglion, A3, the pterothoracic ganglion appears to be the source of a factor that permits these neurons to die according to their usual developmental schedule. PMID- 1634884 TI - Directional control of neurite outgrowth from cultured hippocampal neurons is modulated by the lectin concanavalin A. AB - Cell surface carbohydrates play an important role in the regulation of neurite outgrowth during neuronal development. We have investigated the actions of the plant lectin concanavalin A (Con A), a carbohydrate-binding protein, on neurite outgrowth from hippocampal pyramidal neurons in primary cell culture. Neurons plated in culture medium containing nanomolar concentrations of Con A have a larger number of primary neurites arising directly from the cell soma than do neurons plated in culture medium alone. Furthermore, Con A causes counterclockwise turning of neurites in over 70% of the cultured neurons. Both of these effects of Con A are blocked by the hapten sugar alpha-methyl-D mannopyranoside, suggesting that they result from the interaction of Con A with a cell surface carbohydrate. Another lectin with a different sugar specificity, wheat germ agglutinin, does not modulate neurite outgrowth. Analysis of neurite outgrowth using video-enhanced microscopy reveals that the counterclockwise turning is accompanied by directionally biased extension of filopodia from the growth cones of growing neurites. Treatment of the neurons with cytochalasin, which disrupts actin polymerization, eliminates the neurite turning induced by Con A, suggesting that actin microfilaments are involved in directional control of neurite outgrowth. PMID- 1634886 TI - Modifications of motoneuron development following transplantation of thoracic spinal cord to the lumbar region in the chick embryo: evidence for target-derived signals that regulate differentiation. AB - In order to examine the role of target cells in the development of spinal motoneurons, the neural tube from thoracic segments was transplanted to the lumbar region on embryonic day (E) 2, and allowed to innervate hindlimb muscles in the chick embryo. When examined at later stages of development, the proportion of white and gray matter in the thoracic transplant was altered to resemble normal lumbar cord. Many thoracic motoneurons were able to survive up to posthatching stages following transplantation. The branching and arborization of dendrites of thoracic motoneurons innervating hindlimb muscles, as well as motoneuron (soma) size, were also increased to an extent approximating that seen in normal lumbar motoneurons. In support of previous studies using a similar transplant model, we have also found that the peripheral (intramuscular) branching pattern of thoracic motoneuron axons innervating hindlimb muscles was similar to that of normal lumbar motoneurons. Axon size and the degree of myelination of transplanted thoracic motoneuron axons were also increased so that these parameters more closely resembled axons of normal lumbar than normal thoracic spinal motoneurons. Virtually all of the changes in motoneuron properties noted above were observed irrespective of whether or not the transplanted spinal cord had developed in anatomical continuity with the host rostral cord. Accordingly, it is unlikely that the changes in the development of transplanted thoracic motoneurons reported here are induced either entirely, or in part, by signals derived from the host central nervous system. Rather, these changes appear to be mediated by interactions between the transplanted motoneurons and the hindlimb. We favor the notion that retrograde trophic signals derived from the hindlimb act to modulate the development of innervating motoneurons. Whether this signal involves a diffusible trophic agent released from target cells, or acts by some other mechanism is presently unknown. PMID- 1634887 TI - High vocal center growth and its relation to neurogenesis, neuronal replacement and song acquisition in juvenile canaries. AB - It is generally thought that most circuits of the adult central nervous system (CNS) are sculpted, in part at least, by selective elimination of some of the neurons present in an initial overabundant set. In this scenario, the birth of neurons precedes the period when brain functions, such as learning, first occur. In contrast to this form of brain assembly, we describe here the delayed development of the high vocal center (HVC) and one of its efferent pathways in canaries. The retrograde tracer Fluoro-Gold (FG) was injected into one of HVC's two efferent targets, the nucleus robustus archistriatalis (RA), to define the boundaries of HVC. The HVC grows markedly between 1 and 4 months, invading neighboring territories of the caudal telencephalon. During this same period, 0.43%-0.64% of the HVC neurons present at 1 year of age are labeled per day of [3H]-thymidine injection. [3H]-Thymidine labeling is a marker of cell birth, and during the first 4 months HVC neuron number increases, probably accounting for part of the HVC growth observed. Thereafter, the number of HVC neurons remains constant, but neuronal birth persists. We infer from this that neuronal replacement starts as early as 4 months after hatching and perhaps before then. About half of the neurons born after posthatching day 10 grow an axon to RA to form the main efferent pathway exiting from HVC. HVC growth, neurogenesis, axogenesis, and the observed replacement of neurons happen during the period of juvenile vocal learning. However, the recruitment of neurons that are still present at 1 year shows no particular inflections corresponding to the various stages in song learning, and continues at essentially the same rate after the more stereotyped adult song has been acquired. We suggest that a combination of neurogenesis and neuronal replacement provides unique advantages for learning. PMID- 1634888 TI - Transient neonatal denervation alters the proliferative capacity of myosatellite cells in dystrophic (129ReJdy/dy) muscle. AB - It has been previously shown that transiently denervated, neonatal dystrophic muscle fails to undergo the degeneration-regeneration cycle characteristic of murine dystrophy (Moschella and Ontell, 1987). Thus, the myosatellite cells (myogenic stem cells) in these muscles have been spared the mitotic challenge to which dystrophic myosatellite cells are normally subjected early in the time course of the disease. By in vitro evaluation of the proliferative capacity of myosatellite cells derived from extensor digitorum longus (EDL) muscles of 100 day-old genetically normal (+/+) and genetically dystrophic [dy/dy (129ReJdy/dy)] mice and from muscles of age-matched mice that had been neonatally denervated (by sciaticotomy) and allowed to reinnervate, it has been possible to directly determine whether the cessation of spontaneous regeneration in older dy/dy muscles in vivo, is due to an innate defect in the proliferative capacity of the myosatellite cells or exhaustion of the myosatellite cells' mitotic activity during the regenerative phase of the disease. This study demonstrates that transient neonatal denervation of dystrophic muscle (Den.dy/dy) increases the number of muscle colony-forming cells (MCFs) per milligram of wet weight muscle tissue, increases the plating efficiency, and significantly increases the in vitro mitotic activity of dystrophic myosatellite cells toward normal values. The increased mitotic capability of myosatellite cells derived from Den.dy/dy muscle as compared to unoperated dy/dy muscle suggests that there is no innate defect in the proliferative capacity of the myosatellite cells of dy/dy muscles and that the cessation of spontaneous regeneration in the dy/dy muscles is related to the exhaustion of their myosatellite cells' mitotic capability. PMID- 1634889 TI - Development of coordinated movement in chicks: II. Temporal analysis of hindlimb muscle synergies at embryonic day 10 in embryos with spinal gap transections. AB - Spinal neural circuits can recruit muscles to produce organized patterns of activity early in embryonic development. In a previous study, using multichannel electromyographic (EMG) recordings, we characterized burst parameters for these patterns in the legs of chick embryos during spontaneous motility in ovo at embryonic days (E) 9 and E10 (Bradley and Bekoff, 1990). Results of the study suggested both neural and biomechanical factors play an important role in the development of coordinated limb movements. In this study, to explore the contribution of descending neural inputs to the control of leg movements during motility, we applied similar methods to characterize motor patterns produced by the spinal cord in the absence of descending inputs. Thoracic spinal gap transections were performed at E2 and EMG patterns were recorded at E10. Several EMG features for chronic spinal embryos were similar to those for normal embryos and demonstrate that lumbar spinal circuits can be correctly assembled to control limb movements in the absence of connectivity with more rostral neural structures during early differentiation processes. However, certain aspects of the EMG patterns in chronic spinal embryos were different from patterns in normal embryos and provide support for conclusions drawn earlier by Oppenheim (1975). Specifically, our data support the view that propriospinal and/or supraspinal inputs function to regulate the timing of cyclic limb movements controlled by spinal neural circuits. Finally, we consider the possible long-term effects of chronic spinal gap transections as compared to acute spinal transections on the development of motility. PMID- 1634890 TI - S100 is present in developing chicken neurons and Schwann cells and promotes motor neuron survival in vivo. AB - We used polyclonal antisera recognizing S100, a small acidic protein highly enriched in nervous tissue, to stain sections of embryonic chicken lumbosacral spinal cord and hindlimb. S100 immunoreactivity was detected in developing sensory neurons of the dorsal root ganglia (DRG) and motor neurons of the ventral spinal cord as early as embryonic day (E) 5, and staining persisted through hatching. In contrast, expression of S100 first became apparent in Schwann cells at E13, just before myelination, and was not detected in developing skin or muscle. Since S100 beta was present in motor and sensory neurons and is known to promote neuronal survival and neurite extension in vitro (Winningham-Major, Staecker, Barger, Coats, and Van Eldik, 1989), we tested the ability of S100 to promote neuron survival in an in ovo survival assay. Addition of S100 to chick embryos in ovo during the period of naturally occurring motor neuron cell death resulted in a significant increase in motor neuron survival, but had no effect on the in vivo survival of sensory neurons in the DRG. The findings that S100 is present in spinal motor neurons and that the addition of S100 enhances the survival of these cells in vivo are consistent with the possibility that S100 may act as a naturally occurring neuron survival factor during development. PMID- 1634891 TI - Mossbauer effect studies on some bioinorganic complexes of europium. AB - The bioinorganic complexes of europium with N-acetyl-DL-alanine, N-acetyl-DL valine, and DL-alanyl-DL-alanine have been synthesized and the Mossbauer spectra at room temperature have been measured for these solid state complexes. The Mossbauer parameters indicate that the water molecules in these complexes are not directly linked to the central europium ion and are outside the coordination sphere of europium and biological ligands, and that the chemical bond between the europium ion and the ligands may be predominantly ionic in character, with the possibility of partial covalent contribution. PMID- 1634892 TI - On the use of iron octa-alkylporphyrins as models for protoporphyrin IX containing heme systems in studies employing magnetic circular dichroism spectroscopy. AB - The magnetic circular dichroism (MCD) properties of numerous oxidation and ligation state derivatives of myoglobin and horseradish peroxidase reconstituted with an iron octa-alkylporphyrin (mesoheme IX) have been investigated in order to establish the utility of such porphyrins as models for protoporphyrin IX containing systems. The MCD spectra of the mesoheme-reconstituted proteins are blue-shifted (4-12 nm) and are somewhat more intense (1.5-2.5 fold) when compared to the spectra of analogous derivatives of native myoglobin and horseradish peroxidase. However, the spectral band patterns of the mesoheme-reconstituted proteins closely resemble those of the native proteins in essentially all cases. These data demonstrate that octa-alkylporphyrins can be productively used as models for protoporphyrin IX in studies of heme proteins with MCD spectroscopy. PMID- 1634893 TI - Synthesis, characterization, and antitumor activity of new chloroethylamine platinum complexes. AB - A series of cis-bis-(2-chloroethylamine)platinum(II) and platinum(IV) complexes were synthesized and characterized by elemental analysis, IR, and 1H and 195Pt NMR spectroscopic techniques. Complexes were tested in vitro against murine L1210 leukemia and human ovarian A2780 cell lines and in vivo against the L1210 leukemia model. Some of these complexes showed excellent antitumor activity in both systems. However, all were inactive against cisplatin-resistant A2780/CP cells. PMID- 1634894 TI - Vascular dementia: neuropathologic alterations and metabolic brain changes. AB - After reviewing the concepts of dementia, in general, and vascular dementia, in particular, this review discusses potential future approaches that may contribute to an improved definition of the clinical syndrome and the neuropathological features of vascular dementia. Specific brain alterations in high-energy phosphate compounds, as measured by nuclear magnetic resonance, may contribute to the separation between dementias with neurodegenerative diseases and those with ischemic (vascular or hemodynamic) disorders. PMID- 1634895 TI - Transient myoclonic state with asterixis in elderly patients: a new syndrome? AB - We report 7 patients who developed acute co-occurrences of fragmentary generalized myoclonus and asterixis. All patients were elderly and had other chronic diseases. This condition appeared acutely, progressed over several hours and then disappeared in 2-3 days with diazepam administration. No sequelae were noted, although most cases developed recurrences. The myoclonus occurred spontaneously and was slightly enhanced by action. The myoclonus was widely distributed but predominated in the neck, shoulder girdle, and upper extremities. Opsoclonus was not noted. Clinically apparent myoclonus was not evoked by sensory stimuli. Asterixis was observed in the upper extremities in all cases. Asterixis like movements of the protruded tongue were also observed. Neurological findings other than the myoclonus and asterixis were unremarkable. Neither metabolic nor organic abnormalities clearly responsible for this condition were identified. Cerebral potentials preceding the myoclonic jerks recorded in one case suggested that the myoclonus may have been a spontaneous cortical myoclonus. We named this condition a transient myoclonic state with asterixis (TMA). Awareness of this syndrome is clinically important because of its benign nature, although it can recur. PMID- 1634896 TI - Delayed wallerian degeneration in the central nervous system of Ola mice: an ultrastructural study. AB - The ultrastructural features of wallerian degeneration in the optic nerves of the mutant mouse, C57BL/Ola, was compared with that occurring in age matched control mice, to determine whether the previously described defect in the peripheral nervous system was present in the central nervous system as well. On ultrastructural examination, marked delay in the rate of degeneration was seen in the Ola mice nerves seen most clearly at all stages up to 4 weeks post enucleation, following which differences progressively became undetectable. Once degeneration began, however, the pattern and mechanisms were similar to those seen in control animals, with macrophages, oligodendrocytes, and astrocytes apparently behaving similarly. In both the experimental animals and the controls, the rate of degeneration was slower than that seen in the peripheral nervous system. This study confirms a previous electrophysiological study that the defect in this mutant affects axons in both the peripheral and the central nervous systems. PMID- 1634897 TI - Contralateral early blink reflex in patients with facial nerve palsy: indication for synaptic reorganization in the facial nucleus during regeneration. AB - Fifty patients with Bell's palsy and 30 patients with etiologically different symptomatic peripheral facial nerve palsy were studied by means of electrically evoked blink reflexes 1-23 days after onset of paresis. Their results were compared with a normal control group of 30 healthy subjects. In a significant number of patients (64% in Bell's palsy and 53% in symptomatic facial nerve palsy) a contralateral early blink reflex response (R1) could be elicited upon stimulation of the normal side as compared to 13% in the control group. It is suggested that this result may be explained by synaptic reorganization of the facial nucleus leading to functional unmasking of pre-existing crossed trigemino facial reflex pathways during regeneration. This view is in line with previous experimental data in animals on the time course of structural changes in the facial nucleus after lesioning of the ipsilateral facial nerve. PMID- 1634898 TI - Effects of astrocytes, insulin and insulin-like growth factor I on the survival of motoneurons in vitro. AB - We isolated motoneurons from E15 dissociated mouse spinal cord by density centrifugation and planted them onto poly-ornithine-coated coverslips in a growth medium (DMEM/F12) supplemented with progesterone, transferrin, selenium, horse serum and muscle extract. Under these conditions only 28% of the motoneurons survived for 8 days. When living astrocytes on a separate coverslip were introduced into dishes containing motoneurons, there was a two-fold increase in neuronal survival. The addition of insulin and insulin-like growth factor I (IGF I) to such cultures alone or together, still further increased motoneuron survival, but this did not happen in the absence of astrocytes. We conclude that (a) astrocytes exert a trophic role in the survival of spinal motoneurons, (b) the effect does not require physical contact of the cells, and (c) insulin and IGF-1 have neurotrophic activity for motoneurons, an effect possibly mediated by living astrocytes. PMID- 1634899 TI - Myasthenia gravis: T and B cell reactivities to the beta-bungarotoxin binding protein presynaptic membrane receptor. AB - Antibodies against acetylcholine receptor (AChR) can be detected in most patients with myasthenia gravis (MG) and are considered to be involved in the immunopathogenesis of this disease. AChR are isolated from crude receptor preparations by binding to alpha-bungarotoxin (alpha-BuTx). Patients with MG have also antibodies against a second protein tentatively named presynaptic membrane receptor (PsmR), which has been isolated from crude receptor utilizing beta bungarotoxin (beta-BuTx). PsmR could represent another antigen besides AChR relevant for the development of MG. We have now evaluated the T cell reactivity to PsmR in MG and controls by analysing the frequencies of cells which in response to PsmR in short-term cultures secreted interferon-gamma (IFN-gamma). The B cell response to PsmR was analysed in parallel by counting cells secreting anti-PsmR antibodies. Most patients with MG had PsmR reactive T cell in blood with a median number of about 1 per 44,000 mononuclear cells. Cells secreting anti-PsmR antibodies belonging to the IgG and IgA isotypes, less frequently of the IgM isotype were detected in most MG patients. A positive correlation was found between T cells reactive with PsmR and anti-PsmR IgG antibody secreting cells. PsmR reactive T and B cells were also detected in control patients, but at much lower numbers. Our results indicate that MG is accompanied by T as well as B cell responses to PsmR, in addition to the previously recognized responses to AChR. It remains to be shown whether these PsmR reactivities are of pathogenetic importance in MG. PMID- 1634900 TI - Myasthenogenicity in the main immunogenic region of acetylcholine receptor as modified by conformational design: an approach to antigenic synthetic peptides. AB - Myasthenogenic regions in the acetylcholine receptor (AChR) alpha-subunit were studied in view of the conformation-dependent B-cell epitope expected at beta turn and the MHC class II-restricted T-cell epitope expected at alpha-helix. Torpedo AChR alpha 67-76 and alpha 107-116 were synthesized as the main immunogenic region and the site specific for T-cell epitope in Lewis rat, respectively. Model peptides, synthesized by combining these natural sequence segments or by intervening the segment aligned as Asn-Pro-Gly-Gly (NPGG) in natural sequence segments, were tested in terms of antigenic conformation. The model peptide, alpha 107-116.alpha 67-76.alpha 107-116, was immunogenic in the induction of the animal model of myasthenia, accompanied by the anti-peptide antibody cross-reactive with the native AChR. High antigenicity in antibody assays for various peptide- and native AChR-immunized rats was found when the model peptides, alpha 107-116.alpha 67-76 and/or alpha 107-116.NPGG.alpha 67-76 were used for measurement as antigens. Antigenic conformation for the induction of the disease may thus be different from that for the reactivity to antibody. PMID- 1634901 TI - 31P-NMR spectroscopy of skeletal muscle in Becker dystrophy and DMD/BMD carriers. Altered rate of phosphate transport. AB - Muscle energy metabolism was studied by phosphorus nuclear magnetic resonance spectroscopy (31P-NMR) in 6 patients with Becker dystrophy, and in 24 female DMD/BMD carriers (n = 18) and non-carriers (n = 6). At rest all patients showed a high Pi/PCr ratio due to low PCr and high Pi contents, and a high intracellular IpH. 31P-NMR of carriers and non-carriers did not differ from controls. In patients and carriers in-magnet exercise revealed a reduced ability to perform work and Pi/PCr ratios higher than controls for comparable relative levels of steady-state work. Post-exercise Pi recovery was found abnormal in patients and in carriers. The 31P-NMR abnormalities found in the working muscle of both BMD patients and female DMD/BMD carriers indicate a defect of phosphate metabolism that, be it primary or secondary, reflects a deficit of energy metabolism. PMID- 1634902 TI - Development of HTLV-I-associated myelopathy after blood transfusion in a patient with aplastic anemia and a recipient of a renal transplant. AB - We report the development of rapid progressive HTLV-I-associated myelopathy (HAM) after blood transfusion in two immunosuppressed patients, one of whom had aplastic anemia and the other was the recipient of a renal transplant receiving immunosuppressive chemotherapy. Spastic paraparesis developed 11 or 16 months after transfusion and rapidly progressed to a wheelchair-bound state. The present 2 cases suggest that the coexistent immunosuppression may play an important role in the rapid development of HAM in transfusion-acquired cases. PMID- 1634903 TI - Guillain-Barre syndrome associated with high titers of anti-GM1 antibodies. AB - We found high titers of anti-GM1 antibodies (1/1280 or more) in 3 of 14 consecutive patients (21%) with Guillain-Barre syndrome (GBS) and in 2 additional patients who developed GBS, 10-11 days after starting parenteral treatment with gangliosides. Antibodies were IgG in 4 patients and IgM in one, and they all bound to asialo-GM1, and, in 3, to GD1b as well. Although the clinical features in all the patients with high anti-GM1 titers fulfilled the criteria for the diagnosis of GBS and in 4 of them, proteins but not cells were elevated in cerebrospinal fluid, electrodiagnostic studies in 3 patients showed prominent signs of axonal degeneration, that in one case were confirmed by morphological studies on sural nerve biopsy. No recent antecedent infection was reported by these patients, but in 3, including patients treated with gangliosides, anti Campylobacter jejuni antibodies were elevated. In 3 patients a consistent decrease in anti-GM1 levels was observed after the acute phase of the disease suggesting that the frequent occurrence of these antibodies in patients with GBS and their frequent association with a prominent axonal impairment may have pathogenetic relevance. PMID- 1634904 TI - Effects of exogenous monounsaturated fatty acids on fatty acid metabolism in cultured skin fibroblasts from adrenoleukodystrophy patients. AB - The conversion of [1-14C]16:0 to very-long-chain saturated fatty acids (VLCSFA) was greater in fibroblasts from adrenoleukodystrophy (ALD) patients than fibroblasts from normal subjects. Added 23:1(n-9) decreased the formation of VLCSFA from [1-14C]16:0 in ALD fibroblasts to the value found in normal fibroblasts. Chain-elongation as well as extensive chain-shortening of added 20:1(n-9), 22:1(n-9), 23:1(n-9) and 24:1(n-9) occurred in both normal and ALD fibroblasts, with chain-shortening being less in ALD than in normal fibroblasts. Added 18:1(n-9) together with 22:1(n-9) reduced the levels of both VLCSFA and total n-6 and n-3 polyunsaturated fatty acids (PUFA) in normal and ALD fibroblasts. The levels of total (n-6) and (n-3) PUFA but not the levels of VLCSFA were readily restored by culturing the cells in the presence of 18:1(n-9), 22:1(n-9), 18:2(n-6) and 18:3(n-3). The results are consistent with added monounsaturated fatty acids reducing levels of VLCSFA in ALD fibroblasts by depressing their biosynthesis from 16:0. They also support the use of oils rich in long chain monoenes as a dietary therapy for ALD patients but caution that the PUFA status of ALD patients should be monitored with a view to dietary supplementation, if necessary, with PUFA. PMID- 1634905 TI - Dopaminergic insufficiency reflecting cerebral ageing: value of a dopaminergic agonist, piribedil. AB - Amongst the various disturbances of neurotransmission accompanying cerebral ageing, dopaminergic insufficiency is undoubtedly the most constant, the earliest and the most severe. It affects the three ascending dopaminergic systems and may explain many of the motor, emotional, affective and cognitive disorders associated with cerebral ageing. In particular, the psychobehavioural syndrome of cerebral ageing is marked by disorders affecting the capacities for abstraction, conceptualization, reasoning, elaboration of strategies and problem-solving and therefore analogous to those of frontal symptomatology. They probably reflect disafferentation of the frontal lobe, deprived of effective dopaminergic innervation. This hypothesis is supported by the beneficial effects of the dopaminergic agonist piribedil on symptoms of cerebral ageing, particularly on the psycho-behavioural changes. PMID- 1634906 TI - Retinal dopaminergic receptor affinity and ocular pharmacokinetic profile of piribedil. AB - Binding studies on retinal dopamine receptors have revealed the existence of both D1 and D2 receptors. Human retina micro-autoradiographs confirm the distribution of dopaminergic receptors in the plexiform layers. Piribedil, a dopaminergic agonist, is able to bind to D2 receptors, while its metabolite (S584) preferentially displaces D1-specific radioligands. These results demonstrate that piribedil has a dopamine-like pharmacological profile including direct interaction with receptors. When instilled into the rabbit eye, piribedil penetrates rapidly and accumulates in the pigmented epithelia--the iris ciliary body and chorioretina--before being rapidly cleared. Macro-autoradiographs confirm this distribution and show the levels to be compatible with the affinity of piribedil for retinal dopaminergic receptors. PMID- 1634907 TI - Parkinson's disease: pathological mechanisms and actions of piribedil. AB - The cause of the degeneration of dopamine-containing cells in the zona compacta of the substantia nigra in Parkinson's disease remains unknown. The ability of the selective nigral toxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) (via its metabolite MPP+) to destroy nigral dopamine cells selectively by inhibiting complex I of the mitochondrial energy chain may provide a clue. Indeed, recent studies of post-mortem brain tissue have suggested the presence of an on-going toxic process in the substantia nigra in Parkinson's disease leading to excess lipid peroxidation. This appears also to involve a disruption of mitochondrial function since mitochondrial superoxide dismutase activity is increased and there is impairment of complex I. These changes may in turn relate to a selective increase in the total iron content of substantia nigra coupled to a generalised decrease in brain ferritin content. Piribedil is used in the symptomatic treatment of Parkinson's disease and is particularly effective against tremor. Piribedil (and its metabolites) acts as a dopamine D-2 receptor agonist. However, in our studies in contrast to other dopamine agonists, in vivo piribedil interacts with dopamine receptors in the substantia nigra and nucleus accumbens but not those in the striatum. In patients with Parkinson's disease the beneficial effects of piribedil may be limited by nausea and drowsiness. Indeed, in MPTP-treated primates piribedil reverses motor deficits but marked side effects occur. However, pre-treatment with the peripheral dopamine receptor antagonist domperidone prevents the unwanted effects and piribedil produces a profound and longer-lasting reversal of all components of the motor syndrome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634908 TI - Effect of a dopaminergic agonist, piribedil (Trivastal 50 mg LP), on visual and spatial integration in elderly subjects. AB - Dopamine acts as a neuromodulator in the retina. Dopaminergic deficiency of any origin, as observed in elderly subjects, is associated with altered visual performances, and more specifically with altered perception of contrasts. The goal of this study was to compare contrast vision in elderly subjects and young subjects (first phase, n = 20), then to compare this function in elderly subjects before and after 3 months of treatment with a dopaminergic agonist, piribedil (Trivastal 50 mg LP), administered once daily (second phase, n = 20). The perception of contrast was analysed using a test measuring sensitivity to colour contrast yielding threshold values for sensitivity to contrast in eight spatial frequencies and three colours (red, green, blue) and in two directions (horizontal and vertical). The results of the first phase of the study demonstrated that elderly subjects showed a decrease in contrast perception in comparison with young subjects, primarily in the high frequency range, and over the full range of stimulation for direction and colour. In the second phase, elderly subjects, in comparison with young subjects, showed altered visual contrast, again in the high frequency range, but also in the low frequency range for horizontal simulation with red and blue. After 3 months of treatment with piribedil the mean contrast sensitivity threshold, over the entire frequency range, had significantly increased (P less than 0.05) for all stimulations, apart for red in the vertical direction. These results underline the value of treatment with a dopaminergic agonist, piribedil in visual disturbances in patients with dopaminergic deficiency (Parkinson patients or elderly subjects). PMID- 1634909 TI - Activity and acceptability of piribedil in Parkinson's disease: a multicentre study. AB - Several controlled trials have shown that the dopamine agonist, Trivastal (piribedil), is active in the treatment of Parkinson's disease, particularly with regard to tremor. To determine its efficacy as monotherapy in patients previously untreated with levodopa, a 3-month multicentre study was conducted with Trivastal 50 mg LP in 113 patients with idiopathic Parkinson's disease. The study population consisted of 66 men and 47 women, aged 63.1, SD 0.6 (43-79) years with a 2.1, SD 0.2 (1-15) year history of Parkinson's disease. Mean disease stage was 1.82 (1-4) by the Hoehn and Yahr classification. Tremor was the predominant clinical feature in 42 patients; the remaining 71 patients displayed the full parkinsonian syndrom. Trivastal 50 mg LP was prescribed stepwise up to doses of 150-250 (207, SD 6.4) mg/day at the end of 3 months. No concomitant anti parkinsonian medication was given. Patients were clinically assessed at 1, 2 and 3 months on the Webster scale, a specific tremor scale and the HARD depression scale. Mean results were as follows in the 90 patients completing the study. On the Webster scale, tremor fell from 1.7 to 1 (-41%, P less than 0.001), bradykinesia from 1.5 to 0.8 (-47%, P less than 0.001) and rigidity from 1.3 to 0.9 (-31%, P less than 0.001); on the specific scale, rest tremor decreased in daily duration and amplitude from 3.9 to 2.4 (-39%, P less than 0.001) and from 2.9 to 2.1 (-35%, P less than 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634910 TI - Deterioration of dopaminergic pathways and alterations in cognition and motor functions. AB - Degeneration of central dopaminergic neurons is the most characteristic pathological feature of Parkinson's disease. It remains to be established to what extent these lesions explain the motor, cognitive and affective disorders observed in patients, but there are now some interesting clues to a possible solution. PMID- 1634911 TI - Predictive testing for inherited mutations in cancer-susceptibility genes. PMID- 1634912 TI - Combined modality therapy of rectal cancer: decreased acute toxicity with the preoperative approach. AB - PURPOSE: We compared the combined radiation therapy (RT) plus chemotherapy segments of two separate parallel phase I trials to determine if combined pelvic RT, fluorouracil (5-FU), and high-dose leucovorin (LV) had less acute toxicity when delivered preoperatively versus postoperatively in patients with rectal cancer. PATIENTS AND METHODS: Patients with unresectable disease received preoperative RT plus LV and 5-FU followed by surgery and postoperative LV and 5 FU. Patients with resectable disease received identical doses, techniques, and schedules of RT and LV and 5-FU except all therapy was delivered postoperatively. On day 1, patients received LV and 5-FU times one cycle. RT began on day 8. A second cycle of LV and 5-FU was given concurrently with the fourth week of RT. RESULTS: Although more patients (75% v 32%; P = .02) received the higher dose level of 5-FU (250 mg/m2), significantly fewer experienced acute grade 3 to 4 toxicity with preoperative versus postoperative therapy (13% v 48%; P = .045). There was no grade 3 to 4 myelosuppression in either group. The two grade 3 toxicities in the preoperative group were gastrointestinal. The grade 3 toxicities in the postoperative group included seven gastrointestinal and two genitourinary; four patients had a grade 4 toxicity. CONCLUSION: Given the high incidence of grade 3 to 4 toxicity also reported in the postoperative combined modality adjuvant randomized trials, future adjuvant trials should explore the preoperative approach. PMID- 1634913 TI - Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: a Southwest Oncology Group study. AB - PURPOSE: The Southwest Oncology Group (SWOG) conducted a randomized comparison of cisplatin plus fluorouracil (5-FU) and carboplatin plus 5-FU versus single-agent methotrexate (MTX) in patients with recurrent and metastatic squamous-cell carcinoma (SCC) of the head and neck. The primary objective was to compare separately the response rates of each combination regimen to standard weekly MTX. PATIENTS AND METHODS: Two hundred seventy-seven patients diagnosed with SCC of the head and neck were randomized to one of three treatments: (1) cisplatin 100 mg/m2 intravenously (IV) on day 1 and 5-FU 1,000 mg/m2 per day for a 96-hour continuous infusion repeated every 21 days; (2) carboplatin 300 mg/m2 IV on day 1 and 5-FU 1,000 mg/m2 per day for a 96-hour continuous infusion repeated every 28 days; and (3) MTX 40 mg/m2 IV given weekly. RESULTS: All three treatment regimens were well tolerated. However, both hematologic and nonhematologic toxicities were significantly greater with cisplatin plus 5-FU compared with MTX (P = .001). Toxicity from carboplatin plus 5-FU was intermediate compared with the other regimens. The complete and partial response rates were 32% for cisplatin plus 5 FU, 21% for carboplatin plus 5-FU, and 10% for MTX. The comparison of cisplatin plus 5-FU to MTX was statistically significant (P less than .001), and the comparison of carboplatin plus 5-FU to MTX was of borderline statistical significance (P = .05). Median response durations and median survival times were similar for all three treatment groups. Logistic regression models showed that only treatment assigned was associated significantly with response (P = .001). Cox proportional hazards models indicated that only performance status was associated significantly with survival (P less than .01). CONCLUSIONS: We conclude that combination chemotherapy resulted in improved response rates but was associated with an increased toxicity and no improvement in overall survival. Therefore, new treatments that may alter the course of disease in recurrent head and neck cancer patients still need to be identified. PMID- 1634914 TI - LOPP alternating with EVAP is superior to LOPP alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation trial. AB - PURPOSE: The purpose of this randomized trial was to compare the efficacy of eight cycles of chlorambucil, vincristine, procarbazine, and prednisone (LOPP) with four cycles of LOPP that alternate with four cycles of etoposide, vinblastine, Adriamycin (doxorubicin; Familitalia Carlo Erba, Ltd, UK), and prednisone (EVAP) in patients with advanced Hodgkin's disease. PATIENTS AND METHODS: Between June 1983 and December 1989, 594 patients were entered onto the study. Of the 594, 295 patients were allocated to receive LOPP, and 299 were allocated to receive LOPP/EVAP. RESULTS: The complete remission (CR) rates were 57% and 64%, respectively, after initial chemotherapy (difference not significant [NS]), and 65% and 75%, respectively, after the subsequent administration of radiotherapy to residual masses (P less than .01). The procedure associated mortality in the LOPP and LOPP/EVAP arms was 1% and 3%, respectively. The actuarial CR relapse-free survival was significantly greater in the LOPP/EVAP arm (P less than .001) as was the overall survival (P less than .05). The CR relapse free rate, disease-free survival (DFS) rate, and overall survival rate at 5 years were 52%, 32%, and 66%, respectively, in the LOPP arm, compared with 72%, 47%, and 75% in the LOPP/EVAP arm, respectively. CONCLUSION: These results indicate that LOPP and EVAP is superior to LOPP alone as initial treatment for advanced Hodgkin's disease. PMID- 1634915 TI - Diffuse small cleaved-cell lymphoma: a heterogeneous disease with distinct immunobiologic subsets. AB - PURPOSE AND METHODS: Diffuse small cleaved-cell lymphoma (DSCL) is a relatively uncommon non-hodgkin's lymphoma (NHL) in the United States and has not been the subject of recent in-depth study of factors predictive of outcome. It is unique among the NHL of intermediate grade because there is no evidence of a curable subset of patients. To investigate whether any laboratory data might predict outcome, we studied 33 cases collected during a 12-year period and correlated morphology, immunohistochemistry, and serum lactate dehydrogenase (LDH) with clinical data and outcome. RESULTS: We found that proliferative rate (Ki-67), cell lineage (T v B cell), and serum LDH were associated with significant differences in survival. A Ki-67 value greater than or equal to 20% was associated with a median survival of 20 months compared with 80 months for lower values (P = .0002); patients with tumors of T-cell lineage had a median survival of 20 months compared with 40 months for those with B-cell neoplasms (P = .0143); and a serum LDH greater than 225 IU/L was associated with a median survival of 8 months compared with 40 months for lower LDH levels (P = .0004). Blastoid morphology was also linked to a trend toward poor outcome (P = .08). Neither a history of low-grade lymphoma nor the presence of residual immunologically detectable follicles influenced outcome (P = .93 and .97, respectively). CONCLUSION: We conclude that high Ki-67, high LDH, and T-cell lineage each identify DSCL patients with poor outcome. PMID- 1634916 TI - Abrogating chemotherapy-induced myelosuppression by recombinant granulocyte macrophage colony-stimulating factor in patients with sarcoma: protection at the progenitor cell level. AB - PURPOSE: The purpose of this study was to optimize the dose, schedule, and timing of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) administration that would best abrogate myelosuppression in patients with sarcoma. PATIENTS AND METHODS: Sarcoma patients who had experienced severe myelosuppression after chemotherapy with Cytoxan (cyclophosphamide; Bristol-Myers Squibb Co, Evansville, IN), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and dacarbazine ([CyADIC], cycle 1) were eligible. GM-CSF was administered during a 14-day period until 1 week before cycle 2 of CyADIC and was resumed 2 days after cycle 2 completion. The schedule subsequently was modified to allow the earlier administration of GM-CSF in which CyADIC was compressed from 5 days to 3 days, and GM-CSF was administered immediately after the discontinuation of CyADIC in cycle 2. To understand better the impact of GM-CSF on bone marrow stem cells, the proliferative status of bone marrow progenitors was examined during treatment. To evaluate the effects of GM-CSF on effector cells, select functions of mature myeloid cells were also examined. RESULTS: In the seven patients who were treated on the initial schedule, GM-CSF enhanced the rate of neutrophil recovery; however, severe neutropenia was not abrogated, By using the modified schedule in 17 patients, GM-CSF significantly reduced both the degree and the duration of neutropenia and myeloid (neutrophils, eosinophils, and monocytes) leukopenia. The mean neutrophil and mature myeloid nadir counts were 100/mm3 and 280/mm3 in cycle 1 and 290/mm3 and 1,540/mm3 in cycle 2 (P less than .01 and P less than .001). The duration of severe neutropenia (neutrophil count less than 500/mm3) and myeloid leukopenia (myeloid leukocyte count less than 1,000/mm3) were reduced from 6.2 and 6.8 days in cycle 1 to 2.8 and 1.4 days in cycle 2 (P less than .001). While 16 of 17 patients experienced severe myeloid leukopenia (less than 500/mm3) in cycle 1, only two of 17 experienced severe myeloid leukopenia in cycle 2 (P less than .001). Overall, severe neutropenia was abrogated in seven patients, which made them eligible for dose-escalation of Adriamycin. The fraction of cycling progenitors increased threefold on GM-CSF and decreased dramatically below the baseline within 1 day of GM-CSF discontinuation. CONCLUSIONS: The modified schedule improved the beneficial effects of GM-CSF by enhancing myeloprotection and permitting dose-intensification of chemotherapy. The increased myeloid mass and quiescent progenitors at the initiation of chemotherapy suggest that GM-CSF might allow further chemotherapy dose-rate intensification by shortening the interval between courses. PMID- 1634917 TI - Effective initial therapy of advanced breast cancer with fluorouracil and high dose, continuous infusion calcium leucovorin. AB - PURPOSE: The use of leucovorin (LV) to modulate fluorouracil (FU)-mediated inhibition of thymidylate synthase has been shown both in vitro and in vivo to improve the antitumor activity of this drug. Based on our previous demonstration that this combination was active in heavily pretreated patients with prior FU exposure, we performed a phase II study of FU and high-dose intravenous calcium LV in patients with advanced breast cancer who had been exposed to no more than one prior chemotherapy regimen. PATIENTS AND METHODS: Fifty-one female patients with metastatic breast cancer were entered onto this trial. Patients with metastatic disease limited to soft tissue, lymph nodes, skin, and pulmonary nodules were allowed no prior chemotherapy for advanced disease. Those with metastases in the liver or a lymphangitic pattern on chest x-ray were allowed either a single prior regimen for advanced disease or no therapy for metastatic disease if less than 1 year had elapsed since the completion of adjuvant chemotherapy. FU was given daily for 5 days at 400 mg/m2/d with calcium LV, 500 mg/m2/d, beginning 24 hours before and continuing 12 hours after the first and last FU doses, respectively. RESULTS: The overall objective response rate among 45 eligible patients was 36% (95% confidence interval, 22% to 51%). Fourteen of 31 patients in the soft tissue category responded (45%), and two of 14 in the visceral category experienced an objective response (14%). The median response duration was 5 months. Toxicities were moderate leukopenia and mucositis. CONCLUSIONS: FU plus LV is an active first-line regimen with antitumor efficacy comparable to that of the anthracyclines, which warrants further exploration in combination with other agents active in advanced breast cancer. FU plus LV in this schedule is also an excellent alternative for patients with medical contraindications to more intensive combination chemotherapy regimens. PMID- 1634918 TI - Prognostic significance of progesterone receptor levels in estrogen receptor positive patients with metastatic breast cancer treated with tamoxifen: results of a prospective Southwest Oncology Group study. AB - PURPOSE: Southwest Oncology Group (SWOG) protocol 8228 is a prospective trial designed to investigate the prognostic significance of progesterone receptor (PgR) levels in estrogen receptor (ER)-positive breast cancer patients who were treated with tamoxifen. This study was undertaken because the value of PgR measurements in advanced breast cancer had been assessed previously only in studies that were small, retrospective, or included heterogeneously treated patients. METHODS: Receptor assays were performed only in the laboratories that met strict quality control guidelines. Of the 398 patients entered, 342 patients were eligible and assessable for the study end points of objective clinical response, time to treatment failure, and overall survival. RESULTS: Multivariate analysis shows that elevated PgR levels significantly and independently correlated with increased probability of response to tamoxifen, longer time to treatment failure, and longer overall survival. Overall response rate (defined as complete response [CR], partial response [PR], or stable disease [SD] for greater than 6 months) in this trial was 54%. Response rates to tamoxifen were 43%, 53%, and 61% in subsets of patients with less than 10, 10 to 99, and more than 100 fmol/mg PgR, respectively. Exploratory subset analysis using PgR and other prognostic variables identified ER-positive patient subsets with response rates to tamoxifen ranging from 24% (premenopausal patients) to 86% (postmenopausal patients with ER greater than 38 and PgR greater than 329 fmol/mg). No groups of ER-positive patients were identified who had such a low response rate as to absolutely preclude considering the use of tamoxifen. Multivariate analysis showed the independent, statistically significant predictors were: for response to tamoxifen, menopausal status, PgR, and ER; for time to treatment failure, menopausal status, disease-free interval (DFI), PgR, and ER; and for overall survival DFI, PgR, ER, site of disease, and history of adjuvant therapy. CONCLUSION: We conclude that knowledge of PgR levels together with other clinical information can improve the pretreatment assessment of ER-positive breast cancer patients with metastatic disease. PMID- 1634919 TI - Effects of mastectomy versus lumpectomy on emotional adjustment to breast cancer: a prospective study of the first year postsurgery. AB - PURPOSE: Procedure (mastectomy v lumpectomy) and choice of procedure were examined as predictors of adjustment to breast cancer in a prospective study of the experiences of the first year after surgery. PATIENTS AND METHODS: Breast cancer patients were interviewed the day before surgery, 10 days after surgery, and at the 3-month, 6-month, and 12-month follow-ups. Patients included 24 women who received mastectomy on strong recommendation, 24 who chose mastectomy for other reasons, and 15 who chose lumpectomy. Subjective well-being was assessed in terms of mood disturbance, perceived quality of life, life satisfaction, marital satisfaction, perceptions of social support, and self-rated adjustment. RESULTS: Surgical groups differed in well-being in only one respect: lumpectomy patients reported a higher-quality sex life at 6 and 12 months postsurgery than mastectomy patients. Choice of surgical procedure predicted higher levels of life satisfaction at 3 months. CONCLUSION: The lack of difference between surgical groups in areas other than sexual adjustment replicates previous findings, but extends them by (1) using a fully prospective design, (2) providing data on the period surrounding the surgery (as well as later periods), and (3) examining a broader range of indices of well-being than usual. PMID- 1634920 TI - Infants with neuroblastoma and regional lymph node metastases have a favorable outlook after limited postoperative chemotherapy: a Pediatric Oncology Group study. AB - PURPOSE: Infants less than or equal to 1 year of age with neuroblastoma (NB) have a favorable outlook with minimal to moderate therapy. Patients with complete or partial removal of the primary tumor but positive intracavitary lymph nodes (Pediatric Oncology Group [POG] stage C) have a higher risk for recurrent disease. To determine the importance of distinguishing infants with POG stage C NB from those with POG stage B disease and to assess the efficacy and toxicity of treating POG stage C infants with limited, postoperative chemotherapy, a study was conducted by the POG. PATIENTS AND METHODS: Forty-four eligible POG stage C infants received cyclophosphamide 150 mg/m2 orally on days 1 to 7 and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) 35 mg/m2 intravenously (IV) on day 8 (CYC/ADR), every 3 weeks for five courses followed by second-look surgery. No continuation therapy was given if surgical and pathologic complete response (CR) was achieved. Secondary therapy with five courses of cisplatin 90 mg/m2 on day 1 followed by teniposide (VM-26) 100 mg/m2 on day 3 (CDP/VM) was given to infants with gross residual tumor after CYC/ADR and second-look surgery. RESULTS: Thirty-four infants achieved CR after CYC/ADR alone, three after CYC/ADR and second-look surgery, two after CYC/ADR, surgery, and maintenance therapy, and two after alternative treatment with CDP/VM (total CR rate, 42 of 44). The 3-year survival and disease-free survival are both 93%. Toxicity was nominal. CONCLUSIONS: Infants with POG stage C NB have a favorable outlook, which is similar to infants with POG stage B NB; the surgical staging procedure for distinguishing these infant subsets may not be necessary. Future studies should focus on the reduction of treatment toxicity and efficacy maintenance, and address methods to identify infants at risk for failure. PMID- 1634921 TI - Phase II study of liposomal muramyl tripeptide in osteosarcoma: the cytokine cascade and monocyte activation following administration. AB - PURPOSE: A phase II trial that uses liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) in patients with relapsed osteosarcoma is underway. To determine if in vivo cytokine induction plays a role in the mechanism of action of L-MTP-PE, we investigated the circulating cytokine levels of 16 patients who were undergoing therapy. PATIENTS AND METHODS: Patients had histologically proven osteosarcoma and pulmonary metastases that developed either during adjuvant chemotherapy or that were present at diagnosis and persisted despite chemotherapy. Patients were rendered disease-free by surgery. The major goal of the study was to improve the disease-free interval in this high-risk group. L-MTP-PE 2 mg/m2 was infused during a 1-hour period twice a week for 12 weeks, then once a week for 12 weeks. Serial blood samples were collected after L MTP-PE administration and were assayed for cytokine levels (tumor necrosis factor alpha [TNF alpha] interleukin-1 alpha [IL-1 alpha], IL-1 beta, IL-6, interferon gamma [IFN-gamma], neopterin, C-reactive protein). RESULTS: After the infusion of L-MTP-PE, there was rapid induction of circulating TNF alpha and IL-6. TNF alpha levels peaked 1 to 2 hours after infusion in 10 of 16 patients, whereas peak IL-6 levels were detected at 2 to 3 hours in all patients. Induction of circulating TNF alpha and IL-6 was evident only after the first dose of L-MTP-PE. Neither IL 1 alpha nor IL-1 beta was detected in the plasma. Neopterin levels increased at 24 hours postinfusion, which indicated macrophage activation, and were not related to the induction of circulating IFN-gamma. C-reactive protein was elevated in all patients at 24 hours and decreased by 72 hours. Unlike circulating TNF alpha and IL-6, elevations in C-reactive protein and neopterin could be detected throughout the treatment course. CONCLUSION: It is concluded that L-MTP-PE has specific biologic effects in patients with osteosarcoma that may be important to the drug's immunostimulatory capacity and its effectiveness as an antitumor agent. PMID- 1634922 TI - Refinement of clinicopathologic staging for localized soft tissue sarcoma of the extremity: a study of 423 adults. AB - PURPOSE: The prognostic value of factors used in clinicopathologic staging of localized soft tissue sarcoma (STS) of the extremity were analyzed comprehensively. PATIENTS AND METHODS: Four hundred twenty-three patients with STS that was confined to the extremity were admitted to Memorial Sloan-Kettering Cancer Center from 1968 to 1978. Cox models for the hazards rates of tumor mortality, development of a distant metastasis, strictly local recurrence, and postmetastasis survival were developed. Tests of changes in the prognostic value of the important variables over time were performed, as well as an analysis of the effect of a local recurrence on the hazard rate of distant metastasis. RESULTS: Three unfavorable characteristics contained independent prognostic value for the rates of distant metastasis and tumor mortality: high grade (P less than .00001), deep location (P less than .0002), and size greater than or equal to 5 cm (P less than .007). Their Cox model coefficients did not differ significantly (P greater than or equal to .65); thus, a staging scheme based on the risk of ever developing a distant metastasis would assign equal prognostic weights to grade, depth, and size. The tumor grade effect during the initial 18 months was much larger in magnitude than those for depth and size, and its effect disappeared beyond that time (P = .0003). Thus, a staging scheme based on the risk of early metastatic spread would assign a distinctly larger prognostic weight to grade and lesser but equal weights to depth and size. There was no local recurrence effect on the rate of distant metastasis in the high-risk group (high grade, deep, and greater than or equal to 5 cm; P = .75), but there was a significant association among the remaining groups combined (P = .0039). The magnitude of this association actually increased according to the number of favorable characteristics presented (P = .0024). CONCLUSIONS: The refinement of clinicopathologic staging may depend on the choice of outcome variable: ultimate prognosis versus early metastatic spread. Additionally, the observed local recurrence effect may be explained by a tendency for some patients to acquire one or more unfavorable risk factors at the time of local recurrence. PMID- 1634923 TI - Role of technetium 99m-labeled monoclonal antibody in the management of melanoma patients. AB - PURPOSE: A study was performed to assess the usefulness of a radiolabeled monoclonal antibody (MoAb; technetium 99m NR-ML-05 Fab) as a detecting agent, as well as to evaluate its role in the overall decision-making process in the management of cutaneous malignant melanoma. PATIENTS AND METHODS: Twelve patients with histologically confirmed primary cutaneous melanoma and palpable regional nodes were injected with MoAb NR-ML-05 Fab, radiolabeled with 20 to 30 mCi of 99mTc. Whole-body anterior and posterior images were obtained. Left and right lateral views of the head and anterior and posterior views of the chest, abdomen, pelvis, and extremities were obtained, as were selected single-photon emission computed tomographic (SPECT) views of regional lymph nodes and areas of known or suspected lesions. RESULTS: In nine of 12 patients, clinical and/or MoAb evolution identified 30 discrete sites of suspected melanoma. The remaining three patients showed no positive sites, and there was no evidence of metastatic melanoma. All 30 sites were examined microscopically, and melanoma was confirmed histologically in 23. The remaining seven were negative. MoAb imaging detected 21 (true-positive) but failed to detect two (false-negative) lesions. Sensitivity was 91% (21 of 23); positive predictive value was 95% (21 to 22). CONCLUSIONS: MoAb imaging seems to provide an excellent way to obtain information with regard to the metastatic status of melanoma patients. Immunocytochemistry showed that MoAb (NR-ML-05) is as sensitive as the S-100 antibody and probably more sensitive than the commercially available antimelanoma antibody HMB-45. PMID- 1634925 TI - Interferon-alpha, zidovudine, and granulocyte-macrophage colony-stimulating factor: a phase I AIDS Clinical Trials Group study in patients with Kaposi's sarcoma associated with AIDS. AB - PURPOSE: To increase the hematologic tolerance of interferon-alpha (IFN alpha) and zidovudine combination therapy by the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF), and to evaluate the safety, tolerance, and potential efficacy of the combination in patients with Kaposi's sarcoma and AIDS. PATIENTS AND METHODS: Seventeen patients with Kaposi's sarcoma associated with AIDS received zidovudine 200 mg orally every 4 hours and GM-CSF 5 micrograms/kg/d subcutaneously. Successive cohorts received IFN-alpha 2b at a daily subcutaneous dose of 5, 10, or 20 million units. The dose of GM-CSF was titrated to maintain the neutrophil count between 1 and 5 x 10(9) cells/L. Doses of all three drugs were reduced, as required, for nonhematologic toxicities. RESULTS: GM-CSF induced leukocytosis in all patients. On average, a dose of 1.25 micrograms/kg/d was sufficient to maintain the neutrophil count within the desired range. The combination of 20 million units of IFN-alpha with zidovudine and GM-CSF induced dose-limiting toxicity in four of six patients. The major side effects were constitutional symptoms, which included malaise, anorexia, fatigue, fever, and were dose-limiting in three patients. Severe anemia and/or thrombocytopenia developed in three patients. Seven patients (41%; 95% confidence interval [CI], 18% to 64%) showed objective tumor regression that persisted for a median of 51 weeks. A rapid decrease in free-serum p24 antigen levels was observed in seven patients who had measurable levels at baseline; the mean time required to isolate human immunodeficiency virus (HIV-1) from peripheral-blood cells was increased by 7 days. The number and percentage of CD4-positive lymphocytes showed no significant change. CONCLUSIONS: GM-CSF prevents neutropenia induced by the IFN alpha and zidovudine combination and induced no adverse effects on immune function or HIV activity. However, nonhematologic toxicity precluded a major increase in the maximum-tolerated doses of IFN-alpha and zidovudine. PMID- 1634924 TI - Sequential chemoimmunotherapy in the treatment of metastatic melanoma. AB - PURPOSE: A phase II study that alternates the sequence of chemotherapy (carmustine [BCNU], cisplatin [CDDP], and dacarbazine [DTIC]) and biologic therapy (interleukin-2 [IL-2] and interferon alfa-2 alpha [alpha IFN]) was performed to establish a safe and efficacious way to sequence these forms of treatment for metastatic melanoma. PATIENTS AND METHODS: Patients who had measurable metastatic melanoma, a Karnofsky performance status of greater than or equal to 70, and no clinically significant cardiac or pulmonary dysfunction were eligible for entry onto this trial. Responses to treatment were assessed after a treatment cycle by two tumor evaluations at least 4 weeks apart. RESULTS: Forty two consecutive patients with metastatic melanoma were treated with this sequential chemoimmunotherapy. Transient thrombocytopenia and neutropenia were observed frequently, but neither hemorrhage nor infection occurred in any of the patients. Of the 42 patients, 10 achieved a complete response (24%), 14 achieved a partial response (33%), two achieved a minor response (5%), eight had stable disease (19%), and eight (19%) had progressive disease. The median time to disease progression for all patients was 7 months. The median survival for all patients entered onto the trial was 11.5 months. A vitiligo-like depigmentation was induced in many patients by this treatment. CONCLUSIONS: Cytotoxic chemotherapy can be administered safely immediately before or immediately after IL-2 and alpha IFN. Sequential chemoimmunotherapy administered as previously described yields a response rate of more than 55%. The overall survival curve suggests that a proportion of patients may achieve a long-term benefit from this treatment. Also, cutaneous depigmentation induced by this treatment suggests that immune modulation may contribute to the antimelanoma effect of this treatment. PMID- 1634926 TI - Phase I trial of thiotepa in combination with recombinant human granulocyte macrophage colony-stimulating factor. AB - PURPOSE: The ability of growth factors to stimulate marrow recovery suggests their potential for use in dose intensification of cytotoxic drugs. We performed a phase I study of the alkylating agent thiotepa in combination with granulocyte macrophage colony-stimulating factor (GM-CSF), with the goal of dose-escalation of thiotepa. Thiotepa was selected based on its capacity for dose escalation to more than 1 g/m2 in the marrow transplantation setting. PATIENTS AND METHODS: The starting dose of thiotepa (75 mg/m2) was the highest dose evaluated in our previous phase I trial. Thirteen patients received 22 courses of thiotepa and GM CSF. The dose of GM-CSF was 10 micrograms/kg subcutaneously daily in six patients and 5 micrograms/kg in seven patients. RESULTS: Three patients (23%) developed grade 3 to 4 neutropenia on the first course, with a recovery to more than 1000/mm3 in 4.7 days (mean). Recovery was as rapid with the 5 micrograms/kg as it was with the 10 micrograms/kg GM-CSF dose. Thrombocytopenia grade 3 to 4 affected seven of 13 (54%) patients in the first course; counts recovered to more than 50,000/mm3 in a median of 15 days. GM-CSF at either dose did not influence markedly the severity or duration of thrombocytopenia, and did not permit dose escalation of thiotepa. Among the seven patients who received a second cycle of treatment, six of seven experienced grade 3 or 4 thrombocytopenia that lasted a median of 15.5 days. Five had thrombocytopenia that lasted more than 35 days after one to three cycles of treatment. Plasma concentrations of thiotepa and tepa were measured by gas chromatography in eight patients. The plasma elimination of thiotepa fit a two-compartment open model with a harmonic mean terminal half-life of 2.44 hours. The mean total body clearance was 217.9 mL/min/m2, and the mean steady-state volume of distribution (Vdss) was 36.8 L/m2. The half-life of tepa was 7.98 hours, and the ratio of the area under the plasma concentration versus time curve (AUC) of tepa to that of thiotepa was 0.79. CONCLUSIONS: These data were consistent with our previous observations at this dose, and indicated that the severity of toxicity in these patients was not explained by aberrant pharmacokinetic indices. We conclude that, independent of effects on neutropenia, severe and cumulative platelet toxicity precludes further escalation of thiotepa dose despite the use of GM-CSF. PMID- 1634927 TI - Methotrexate pharmacokinetics following administration of recombinant carboxypeptidase-G2 in rhesus monkeys. AB - PURPOSE: Carboxypeptidase-G2 (CPDG2) is a bacterial enzyme that rapidly hydrolyzes methotrexate (MTX) into inactive metabolites. As an alternative form of rescue after high-dose MTX (HDMTX), CPDG2 has more potential advantages than standard leucovorin (LV) rescue. In this study, the plasma pharmacokinetics of MTX with and without CPDG2 were evaluated in adult rhesus monkeys. MATERIALS AND METHODS: The plasma pharmacokinetics of MTX were determined in groups of animals that had received a 300-mg/m2 loading dose of MTX followed by a 60-mg/m2/h infusion during an 18-hour period. One group received CPDG2 at the end of the infusion, and the other group served as a control. Two additional animals with high titers of anti-CPDG2 antibody also were studied. RESULTS: During infusion, the steady-state MTX plasma concentration was 11.3 +/- 4.8 mumol/L. Without CPDG2, the postinfusion plasma MTX concentration remained above 0.1 mumol/L for more than 6 hours. After the administration of 50 U/kg of CPDG2, plasma MTX concentrations decreased to nontoxic levels (less than 0.05 mumol/L) within 30 minutes. The initial half-life (t1/2 alpha) of MTX decreased from 5.8 +/- 2.1 minutes to 0.7 +/- 0.02 minutes after enzyme administration. The postinfusion area under the plasma concentration time curve of MTX was 301 +/- 171 mumol/L/min without CPDG2 compared with 19.6 +/- 6.1 mumol/L/min with CPDG2. The immunogenicity studies performed indicated that although animals developed anti CPDG2 antibodies, none of them manifested allergic symptoms. The effectiveness of CPDG2 was diminished but not eliminated in animals with high titers of anti-CPDG2 antibody. CONCLUSIONS: CPDG2 is capable of rapidly decreasing plasma MTX concentrations to nontoxic levels. The administration of CPDG2 seems safe, well tolerated, and it may be useful as an alternative to LV rescue. PMID- 1634928 TI - Cisplatin in gynecologic carcinosarcoma. PMID- 1634929 TI - Interleukin-2 therapy with or without lymphokine-activated killer-cell infusions for low-grade non-Hodgkin's lymphomas? PMID- 1634930 TI - Radiation therapy is better than chemotherapy in early-stage Hodgkin's disease? Not so fast. PMID- 1634931 TI - Interpretation of nonsignificant results. PMID- 1634932 TI - Annual meeting highlights: molecules with messages. PMID- 1634933 TI - Strontium-89 and low-dose infusion cisplatin for patients with hormone refractory prostate carcinoma metastatic to bone: a preliminary report. AB - Strontium-89 has been used for the treatment of painful bony metastases in patients suffering from disseminated adenocarcinoma of the prostate, with a variable proportion of patients obtaining clinically significant reductions in analgesic requirements. Based on data revealing enhancement of continuous low dose rate irradiation by low-dose cisplatin in murine models, a protocol using 148 MBq (4 mCi) of 89Sr and 35 mg/m2 of cisplatin infused over 2 days, 1 and 4 wk after administration of the radioisotope was undertaken. Preliminary data suggest good pain relief with 55% of 18 patients entered thus far obtaining at least a 50% reduction in analgesic requirements. Improvements in total alkaline phosphatase and serum lactate dehydrogenase have consistently been seen, with some patients exhibiting improvements in hemoglobin, tumor markers and bone scans. Toxicity appears to be mild, with no life-threatening complications. In particular, myelosuppression after one course of treatment was modest, but retreatments in two patients has resulted in grade 3 hematologic toxicity. Two patients developed a "pain flare" after administration of cisplatin. Further accrual to this study will allow more accurate determination of pain response rate, and improved evaluation of parameters of objective response. PMID- 1634934 TI - Scintigraphic assessment of MIBG uptake in globally denervated human and canine hearts--implications for clinical studies. AB - To further characterize the behavior of metaiodobenzylguanidine (MIBG) in the myocardium and to test the hypothesis that the denervated heart would show normal early uptake on MIBG due to non-neuronal localization, we examined the early and late distribution of 123I-labeled MIBG in normal and globally denervated canine and human hearts. Canine hearts were denervated by intravenous injections of 6 hydroxydopamine, while patients were studied a mean of 4.3 mo following cardiac transplantation. Results in denervated hearts were compared to normal controls. Normal hearts showed prominent MIBG uptake on initial 5-min and 3-hr delayed images. Globally denervated canine hearts showed prominent uptake on initial images and absence of localization on delayed images, indicating complete washout of non-neuronally bound radionuclide. The transplanted human hearts showed no localization of MIBG on either early or delayed images. These results suggest that the non-neuronal uptake mechanism (uptake 2) is not significant in human myocardium. This finding has significant implications for interpreting the myocardial behavior of MIBG in various pathologic situations such as dilated cardiomyopathy. PMID- 1634935 TI - Evaluation of a neural-network classifier for PET scans of normal and Alzheimer's disease subjects. AB - The value of PET as an objective diagnostic tool for dementia may depend on the degree to which abnormal metabolic patterns can be detected by quantitative classification methods. In these studies, a neural-network classifier based on coarse region of interest analyses was used to classify normal and abnormal FDG PET scans. The performance of neural networks and of an expert reader were evaluated by cross-validation testing. When the "abnormal" class was represented by subjects with clinical diagnoses of "Probable Alzheimer's," the areas under the relative-operating-characteristic (ROC) curves were 0.85 and 0.89 for the neural network and the expert reader, respectively. When testing with abnormal subjects represented by "Possible AD" cases, ROC areas for both the network and the expert were 0.81. The neural network out-performed discriminant analysis. It is concluded that PET has potential for the detection of abnormal brain function in dementing diseases, and that the combination of neural networks and PET is a useful diagnostic tool. Despite the low-resolution "view" afforded the neural network, its performance was nearly equivalent to that of an expert reader. PMID- 1634936 TI - Reproducibility of plasma and extracellular fluid volume measurements in critically ill patients. AB - Plasma and extracellular fluid (ECF) volume measurements may provide valuable complementary data to the hemodynamic measurements currently used to compare fluid infusions in critically ill patients. To assess the reproducibility of plasma and extracellular fluid volume measurements in critically ill patients, we injected 131I-labeled albumin (10 microCi) and 35S-sodium sulfate (50 microCi), respectively, into 15 stable patients on two occasions 150 min apart. Plasma was sampled at 20, 30, and 40 min after each injection and the volume of distribution of each radioisotope was calculated from the extrapolated zero time counts. We found that plasma and ECF volume did not differ significantly between the first (42.4 +/- 4.7 ml/kg and 186 +/- 39 ml/kg) and second (42.8 +/- 5.5 ml/kg and 193 +/- 48 ml/kg) measurements. Specifically, the mean difference between the two measurements was 0.4 +/- 3.2 ml/kg and 7 +/- 17 ml/kg respectively. We conclude that measurements of plasma and ECF volume are reproducible over 150 min in stable critically ill patients. PMID- 1634937 TI - The effects of carbidopa administration on 6-[18F]fluoro-L-dopa kinetics in positron emission tomography. AB - Carbidopa (L-alpha-hydrazino-alpha-methyl-b-(3,4-dihydroxyphenyl) propionic acid is a known inhibitor of aromatic amino acid decarboxylase. In both humans and monkeys, we studied the effects of carbidopa on plasma and brain kinetics of 6 [18F]fluoro-L-DOPA (FDOPA), an analog of L-DOPA used for PET studies of the central dopaminergic system. Pretreatment with carbidopa resulted in increases in the plasma levels of FDOPA and 3-O-methyl-6-[18F]fluoro-L-DOPA (3-OMFD). Total striatal and cerebellar activities measured with PET were also increased. Furthermore, increases observed in the specific striatal activity (striatum minus cerebellum total activity) were correlated with increases in the plasma FDOPA curve. Carbidopa pretreatment did not affect the influx rate constant (K) for FDOPA from plasma to striatum in humans as determined by Patlak graphical analysis. Thus, an increase in measured striatal tomographic activity was secondary to the increase in plasma FDOPA levels rather than as a result of changes in the FDOPA influx rate constant. PMID- 1634938 TI - Clinical meaning of circulating antithyroglobulin antibodies in differentiated thyroid cancer: a prospective study. AB - In recent studies of patients with differentiated thyroid cancer (DTC), an association between the persistence of tumor and the presence of circulating anti thyroglobulin antibodies (TgAbs) have been described. The aim of the present study was to evaluate TgAb variations before and after total thyroid ablation and to correlate TgAb levels to the outcome of disease. Forty-three patients with DTC were studied (35 female, 8 male; 33 patients had papillary cancer and 10 follicular cancer). Tumor was intrathyroid in 20 cases, had spread to the lymph nodes in 19 and to the lungs in 4. All patients underwent total thyroidectomy and 131I therapy, and were then treated by suppressive doses of L-thyroxine. After a mean follow-up of 3.55 yr, TgAbs became undetectable in 24 patients (all were considered tumor-free), whereas TgAbs remained elevated in 19 cases. In 5 of these 19 patients, disease progression or persistence was documented (to the lymph nodes in three and to the lungs in two). TgAb levels were higher in patients with persistent disease in comparison with those tumor-free. Serum thyroglobulin (S-Tg) results were only elevated in the two patients with persistent disease in the lungs. Our data suggest that TgAbs determination may give some additional information to the follow-up of patients with DTC: the disappearance of TgAbs after therapy seems to represent a favorable prognostic factor, while the persistence of circulating TgAbs, particularly at high levels and in the absence of detectable S-Tg, may be representative of disease. PMID- 1634939 TI - Leukocyte scintigraphy in the diagnosis of mycotic aneurysm. AB - Early diagnosis of a mycotic aneurysm is critical, but often unsuspected, due to the insidious onset of symptoms related to occult infection. This study was undertaken to assess the role of leukocyte scintigraphy in establishing the diagnosis of mycotic aneurysm. The records of all patients with possible mycotic aneurysm between 1985 and 1991 were reviewed. Seven patients had leukocyte scintigraphy and computed tomography (CT), three also had magnetic resonance imaging (MRI) and three had angiography as part of the diagnostic workup. CT and MRI detected aneurysms in five of the seven patients, but CT scans were misinterpreted in two patients as indicative of abscess only. In six patients, infection could not be differentiated from thrombosis, seroma or hemorrhage by CT or MRI. Leukocyte scintigraphy was positive in all four patients with infected aneurysms; it was negative in two of the three noninfected aneurysms and equivocal in the third. Leukocyte scintigraphy provided a useful early survey that demonstrated evidence of infected aneurysms in four patients and identified other sites of infection in two patients. Leukocyte uptake complemented CT, MRI and angiographic findings distinguishing between seroma/hematoma and adjacent infection to establish a preoperative diagnosis of infected aneurysms. PMID- 1634940 TI - Detection of cardiovascular infections with radiolabeled leukocytes. PMID- 1634941 TI - Rapid gastric emptying of an oral glucose solution in type 2 diabetic patients. AB - Gastric emptying of a liquid glucose meal was measured with scintigraphic techniques in nine recently diagnosed Type 2 diabetic patients and nine sex- and age-matched nondiabetic control subjects. Seven of the nine Type 2 diabetic patients were receiving oral hypoglycemic therapy which was discontinued the evening prior to the study. The other two diabetic patients were taking no medication. The average gastric half-emptying time was 33.6 min (s.e.m. = 3.2) for the diabetic patients and 64.6 min (s.e.m. = 4.2) for the nondiabetic controls (p = 0.0005). These measurements indicate rapid gastric emptying in Type 2 diabetic patients which may contribute to worsening of glucose control in these patients. PMID- 1634942 TI - Time course of myocardial infarction evaluated by indium-111-antimyosin monoclonal antibody scintigraphy: clinical implications and prognostic value. AB - To investigate the clinical implications of 111In-antimyosin antibody scintigraphy in the chronic stage of myocardial infarction, 34 studies were performed in 26 patients with 36 infarcts of various infarct ages. The infarcts were divided into three groups according to time from onset of chest pain to scintigraphy. Positive antimyosin images were obtained in 93% of Group I patients (3 days to 1 mo), 71% of Group II patients (1.5 mo to 1 yr) and none were obtained from Group III patients (1.5-6 yr). A negative correlation was observed between antimyosin uptake and the time after myocardial infarction. In Group II, patients with coronary artery patency and patients showing redistribution on exercise 201TI scintigraphy were more likely to have positive antimyosin images compared to patients without these features. Recurrent angina may also relate to chronic antimyosin uptake. Indium-111-antimyosin antibody scintigraphy may be a useful method in assessing the course of myocardial infarction and for the patient follow-up. PMID- 1634943 TI - Quantitative stress-redistribution thallium-201 SPECT using prone imaging: methodologic development and validation. AB - Prone 201Tl myocardial perfusion SPECT has been shown to improve left ventricular inferior wall counts compared to supine imaging, thus minimizing diaphragmatic attenuation. Prone SPECT quantitative normal limits were developed and prospectively applied to 36 patients who had coronary angiography. The prone imaging table used had a cut-out under cardiac area which increased the average myocardial counts by 10.7% compared to prone SPECT through the standard table. Overall specificity and sensitivity were 80% and 93%, respectively. For the right, left circumflex and left anterior descending coronary arteries, the specificities were 94%, 71%, and 94%; and sensitivities were 88%, 89% and 78%, respectively. The normalcy rate in 55 normal patients was 89%. Incidence and the severity of patients motion in 200 prone SPECT studies were compared to 200 supine SPECT studies. Mild and severe motion occurred in 12% and 4% of the supine studies and in only 3.5% and none of the prone studies, respectively. When compared to supine SPECT, prone SPECT had higher (p less than 0.01) regional counts/pixel in the inferior wall and septum, but required an average increase of 2.9 +/- 1.0 cm in camera to chest wall distance and resulted in a reduction of total myocardial counts. Prone SPECT provides an alternative approach for patients who cannot tolerate supine imaging. It should be considered when inferior wall defects on supine imaging pose a diagnostic dilemma and when motion on supine imaging necessitates repeat acquisition. PMID- 1634944 TI - Subcellular distribution and analysis of technetium-99m-MIBI in isolated perfused rat hearts. AB - To address the apparent discrepancy between cultured cells and whole heart preparations, Langendorff-perfused rat hearts loaded with hexakis (2 methoxyisobutyl isonitrile) technetium (I) (99mTc-MIBI) were fractionated by a standard differential centrifugation method and fractional contents of 99mTc-MIBI were correlated with the mitochondrial marker, malate dehydrogenase (MDH), and mitochondrial substrates. The "cytosolic" fraction nominally contained 89% +/- 3% of total 99mTc-MIBI, but also contained 91% +/- 1% of total MDH activity by this method. Chromatographic analysis of activity in the "cytosolic" fraction demonstrated greater than 95% of the agent was present as the original free cationic complex; binding to a small molecular weight cytosolic protein was not involved in localization. Addition of the mitochondrial uncoupler CCCP (5 microM) to both "mitochondrial" and "cell fragment" pellets released up to 84% +/- 8% of 99mTc-MIBI content and addition of the mitochondrial substrate succinate (10 microM) in the presence of rotenone (1 microM) enhanced 99mTc-MIBI content by up to 139% +/- 52% over the control. These correlative data from rat hearts indicate that approximately 90% of 99mTc-MIBI activity in vivo is associated with mitochondria in an energy-dependent manner as a free cationic complex, but migrates during fractionation/centrifugation. PMID- 1634945 TI - Time course of skeletal muscle glucose uptake during euglycemic hyperinsulinemia in the anesthetized rabbit: a fluorine-18-2-deoxy-2-fluoro-D-glucose study. AB - Since skeletal muscle has been implicated as the major site of insulin resistance, the purpose of this study was to examine in detail the time course of muscle glucose uptake during the onset and maintenance of euglycemic hyperinsulinemia. Uptake of 18F-2-deoxy-2-fluoro-D-glucose (FDG) by the thigh muscle of an anesthetized rabbit was monitored by a single pair of coincidence photon detectors. Graphical analysis of tissue and plasma radioactivity concentrations was performed to derive fractional rates of FDG phosphorylation continuously. FDG phosphorylation rates were determined during rest (glucose 7 mM, insulin 5-10 microU/ml) and subsequent 5-min intervals under conditions of euglycemic hyperinsulinemia (glucose 6-8 mM; insulin 350-400 microU/ml plasma). FDG phosphorylation did not increase above resting control levels until 5.5 +/- 1.5 min after intravenous insulin administration. After 20-30 min of hyperinsulinemia, FDG phosphorylation and calculated glucose metabolic rates were increased by 50%. At 35-40 min of the clamp in place, there was a second increase in tracer phosphorylation which plateaued at 200% of control (p less than 0.01) and remained at this level for the remainder of the experiment. In conclusion, we have described a method for making rapid, serial estimates of insulin-mediated skeletal muscle glucose uptake. We suggest that appraisal of the time course of glucose uptake with FDG will aid in the understanding of normal and pathophysiologic states of insulin action in vivo. PMID- 1634946 TI - 5-Iododeoxyuridine increases the efficacy of the radioimmunotherapy of human tumors growing in nude mice. AB - Recently, there has been much interest in the use of radionuclide conjugated monoclonal antibodies for the treatment of human malignancies. One way to potentially maximize the therapeutic effectiveness of radioimmunotherapy would be to sensitize tumor cells to the radiation dose delivered by the antibody. Since radioimmunotherapy can potentially treat disseminated disease, including micrometastasis, we chose to study a halogenated pyrimidine radiosensitizer, a class of compounds that affect nonhypoxic cells. 5-Iododeoxyuridine, administered with pyrimidine metabolism modulators, increased the therapeutic effectiveness of radioimmunotherapy, resulting in individual cures of human tumors growing in BALB/c nu/nu (nude) mice. 5-Iododeoxyuridine was administered with N (phosphonacetyl)-L-aspartic acid and 5-fluoro-deoxycytidine plus tetrahydrouridine. This drug treatment was combined with radioimmunotherapy using 131I conjugated to a monoclonal antibody, Mc5. Mc5 binds to a mucin component of the human milk fat globule. This antigen is expressed on the surface of MX-1 cells, the transplantable human tumor used in this study. Tumor-bearing mice treated with both the drug protocol and 131I-Mc5 (540 microCi, 10 microCi/micrograms) showed a regression in average tumor volume. The average tumor volume was reduced below the initial size at treatment for 50 days; two of five cures were obtained. Neither cures nor regressions were observed with either the drug or antibody treatments alone. Our results indicate the potential for increasing the therapeutic effectiveness of radioimmunotherapy of human solid tumors with halogenated pyrimidines. PMID- 1634947 TI - Fluorine-18-labeled monoclonal antibody fragments: a potential approach for combining radioimmunoscintigraphy and positron emission tomography. AB - Monoclonal antibody fragments labeled with 18F could be useful for PET if selective tumor uptake could be achieved within a few half-lives of this nuclide. To evaluate this possibility, the F(ab')2 fragment of Mel-14, an antibody reactive with gliomas and other tumors, was labeled by reaction with N succinimidyl-4-[18F]fluorobenzoate. The in-vitro binding properties of 18F labeled Mel-14 F(ab')2 were nearly identical to those observed when this F(ab')2 was labeled by reaction with N-succinimidyl-4-[125I]iodobenzoate (18F, affinity constant = (6.7 +/- 1.1) x 10(8) M-1; 125I, affinity constant = (8.8 +/- 0.6) x 10(8) M-1). The tissue distribution of the two labeled fragments was compared in paired-label studies performed in athymic mice with subcutaneous D-54 MG human glioma xenografts. Uptake of both nuclides in tumor was rapid with levels as high as 18.7% +/- 1.1% injected dose/g for 18F and 19.4% +/- 1.0% injected dose/g for 125I observed by 4 hr after injection. Tumor-to-normal tissue ratios for 18F labeled Mel-14 F(ab')2 at 4 hr ranged between 0.8:1 for kidneys to 40:1 for brain. These results suggest that it may be feasible to use 18F-labeled antibody fragments for imaging tumors with PET. PMID- 1634948 TI - Relationship between quantitative tumor scintigraphy and time to metastasis in dogs with osteosarcoma. AB - Parameters that predict tumor aggressiveness or response to therapy are potentially useful in selecting the most appropriate treatment. In theory, the biologic aggressiveness of an untreated bone tumor may be reflected in bone scan parameters. The purpose of this study was to assess the usefulness of bone scintigraphy as a predictive indicator of subsequent metastasis in 25 dogs with primary osteosarcoma. Dogs received radiotherapy and/or intra-arterial cisplatin prior to limb-sparing surgery. Quantitative bone scintigraphy of the tumor was performed prior to treatment (25 dogs) and following treatment but prior to limb sparing surgery (22 dogs). All dogs developed metastasis at a median time of 202 days (range, 41-444 days) after initiation of treatment. A statistically significant relationship was identified between time to metastasis and: (1) the radiographic tumor area, (2) the pretreatment ratio of mean counts per pixel in tumor-to-adjacent nontumor bone (T/NTT), and (3) the pre:post-treatment T/NTT. Larger tumor area and high pretreatment tumor activity were associated with earlier metastasis. Tumors characterized by greater decreases in scintigraphic uptake after treatment were associated with earlier metastasis. These data suggest that osteosarcomas with high pretreatment mean counts per pixel signify aggressive tumors subject to early metastasis. PMID- 1634949 TI - Diagnosis of bleeding mycotic iliac aneurysm on technetium-99m renal scan. AB - Since abdominal aneurysms are common in the elderly, it is not unusual to see incidental aneurysms on renal scintigraphy performed for other reasons. However, the initial discovery of a bleeding aneurysm on a renal scan in a patient with salmonella septicemia who has no other obvious focus of infection should be considered suspicious for mycotic aneurysm. A prompt diagnosis is crucial to avoid catastrophic outcome associated with delayed surgical intervention. PMID- 1634950 TI - Scintigraphic aspect of Rotor's disease with technetium-99m-mebrofenin. AB - A 28-yr-old male with Rotor's disease was studied with 99mTc-mebrofenin. The scintigraphic pattern was that of a slow liver uptake with unimpaired excretion and persistent visualization of the cardiac blood pool, kidneys and urinary tract up to 6 hr. The gallbladder was visualized at 55 min postinjection. PMID- 1634951 TI - Hepatic clearance of technetium-99m-iminodiacetic acid derivatives in hyperbilirubinemic states. PMID- 1634952 TI - Indium-111 imaging of an inflammatory abdominal aortic aneurysm. AB - Indium-111-labeled leukocyte scanning has been shown to be a highly sensitive and specific imaging modality in the detection of abscess formation. Leukocyte infiltration occurs in a variety of inflammatory states as well as some noninflammatory states, leading to false-positive results. We report a case of an inflammatory abdominal aortic aneurysm imaged by 111In. It is not clear whether the activity noted is due to the inflammatory nature of the aneurysm or to hemorrhage present within the wall of the aneurysm. PMID- 1634953 TI - Reversible thallium-201 perfusion defects of the septal and inferoapical segments in a patient with incomplete right bundle branch block and normal coronary angiogram. AB - Possible causes of reversible perfusion defect in exercise-rest 201Tl myocardial images in a patient with a normal coronary artery angiogram include left bundle branch block, coronary spasm, myocardial bridges, hypertrophic cardiomyopathy, mitral valve prolapse, aortic valve disease and anomalous origin of the left coronary artery arising from the pulmonary artery. This case is a report of a 34 yr-old man with incomplete right bundle branch block and angiographically normal coronary arteries who was found to have reversible defects involving septal and inferoapical walls on stress-rest 201Tl-chloride myocardial imaging. PMID- 1634954 TI - Acute onset of cardiogenic shock associated with normal coronary arteries, diffuse myocardial necrosis, and rapid clinical recovery. PMID- 1634955 TI - Effect of patient motion on tomographic myocardial perfusion imaging. AB - We evaluated the effect of patient motion on inducing false-positive tomographic 201Tl myocardial perfusion studies. The effects of the angle of camera rotation at which movement occurs, the direction of movement and the distance of movement were studied. Movement was stimulated by shifting the raw data from normal motion free 201Tl tomographic myocardial perfusion studies. The visual detectability of motion artifact was evaluated with receiver-operating characteristic curve analysis. The clinical importance of patient movement was determined by measuring the incidence of quantitative bull's-eye abnormalities induced by motion. Visual artifacts were more detectable and quantitative abnormalities more frequent as the distance of movement increased. Artifacts from 3.25 mm of movement were not visually detectable. Artifacts from 6.5 mm of movement were visually detectable, but were infrequently clinically important. Movement of 13 mm or greater frequently caused quantitative abnormalities. Quantitative abnormalities from axial movement were more frequent than artifacts from lateral movement. Quantitative abnormalities were more frequent when the movement occurred at the beginning or end. We conclude that when patients move during 201Tl tomographic myocardial perfusion imaging, the incidence and character of false-positive results depend on the angle of camera rotation at which the movement occurs, the direction of the movement and distance of the movement. PMID- 1634956 TI - Sensitivity of SPECT thallium-201 myocardial perfusion imaging to patient motion. PMID- 1634957 TI - Attenuation correction of thallium SPECT using differential attenuation of thallium photons. AB - The greatest limitation of 201Tl for the diagnosis of coronary artery disease remains the high soft-tissue attenuation of its low energy photons. However, thallium also emits a smaller number of higher energy photons. Since photons of higher energy undergo less attenuation, it was postulated that the amount of attenuation could be ascertained from the ratio of the low-to-high energy photon counts. A planar phantom was used to derive a regression equation relating attenuation to the count ratio of the low and high energy peaks. A three dimensional heart phantom was constructed and SPECT images were obtained in air and water. Application of the attenuation correction algorithm to the SPECT images of the phantom in water produced images quantitatively similar to that obtained in air. We conclude that by using differential photon attenuation, correction of 201Tl SPECT using a single order post-processing technique is feasible. This technique may allow for more accurate analysis of thallium myocardial perfusion scintigraphy. PMID- 1634958 TI - Of theoretical derivations and empirical evidence. PMID- 1634959 TI - An automated method for rotational correction and centering of three-dimensional functional brain images. AB - The display and analysis of functional brain images often benefit from head rotational correction and centering. An automated method was developed to align brain PET images into a standard three-dimensional orientation. The algorithm performs transverse and coronal rotational correction as well as centering of a brain image set. Optimal rotational correction and centering are determined by maximizing a bilateral hemispheric similarity index, the stochastic sign change criterion. Testing of this algorithm on simulated symmetrical brain image sets showed errors less than 1.0 degree and 0.5 pixels for rotational correction and centering, respectively. With actual PET data, the algorithm results correlated well with those obtained by visual inspection. Testing on asymmetrical brain image sets with simulated lesions indicated that performance of the algorithm is not sensitive to focal asymmetries. This automated method provides objective, reproducible image alignment into a standard orientation and facilitates subsequent data analysis techniques for functional brain images. PMID- 1634960 TI - Does PET offer little additional value when compared with SPECT? PMID- 1634961 TI - Science behind clinical PET. PMID- 1634962 TI - The role of gallium scanning in staging lymphoma. PMID- 1634963 TI - The case for calcium antagonists as first-line treatment of hypertension. AB - OBJECTIVES: The evidence in favour of using calcium antagonists as first-line treatment for hypertension was reviewed. Without performing a comprehensive meta analysis, an evaluation was made of the favourable effects of these agents on cardiovascular risk factors other than the reduction in blood pressure. BACKGROUND: Hypertension is a disease of the elderly, in whom calcium antagonists are particularly effective. These agents do not have the adverse effects on lipids or insulin resistance seen with thiazides or beta-blockers. MODE OF ACTION: Promising new data show that the development of atherosclerosis can be slowed by interference with endothelial and platelet mechanisms, inhibition of vascular smooth muscle proliferation, binding of lipoproteins and hydrolysis of cholesterol esters in liposomes. CONCLUSIONS: On the grounds of superior efficacy in the target patient population, together with favourable effects on other important factors in the genesis of atherosclerosis, calcium antagonists are the drugs of choice for first-line therapy and are also readily combined with the other major classes of antihypertensive drugs. PMID- 1634964 TI - Psychophysical derivation of the impulse response through generation of ultrabrief responses: complex inverse estimation without minimum-phase assumptions. AB - A new technique is presented for the psychophysical measurement of the response phase that requires no assumptions of the relation between the phase and amplitude components of the frequency response. The amplitude attenuation is measured by a standard threshold paradigm and is then compensated for by increasing harmonic strength in proportion to the visual attenuation. Then the phase of each frequency component is adjusted to maximize the internal response amplitude. The amplitude and phase values may be converted by inverse Fourier transformation into the estimated visual impulse response in any stable set of stimulus conditions and are insensitive to a wide variety of response nonlinearities. A key aspect of the phase measurement technique is the generation of a stimulus to obtain the minimum time spread of the internal response, creating a briefer response than for any other stimulus. PMID- 1634965 TI - Blind deconvolution of quantum-limited incoherent imagery: maximum-likelihood approach. AB - Previous research presented by the author and others into maximum-likelihood image restoration for incoherent imagery is extended to consider problems of blind deconvolution in which the impulse response of the system is assumed to be unknown. Potential applications that motivate this study are wide-field and confocal fluorescence microscopy, although applications in astronomy and infrared imaging are foreseen as well. The methodology incorporates the iterative expectation-maximization algorithm. Although the precise impulse response is assumed to be unknown, some prior knowledge about characteristics of the impulse response is used. In preliminary simulation studies that are presented, the circular symmetry and the band-limited nature of the impulse response are used as such. These simulations demonstrate the potential utility and present limitations of these methods. PMID- 1634966 TI - Motion recovery in light-attenuating media from image-shading variations. AB - One of the requirements for providing some autonomy in the operation of robotic vehicles is an accurate knowledge of position, orientation, and motion relative to nearby objects and the environment. Passive-vision sensing provides a useful tool for extracting such information from the images of the scene. Some applications, including the operation of undersea vehicles, involve working under artificial lighting in an attenuating medium. The extraction of motion, position, and orientation information requires models of image brightness that incorporate the effects that are due to the illumination attenuation and the illumination variation resulting from the motion of the light source. We investigate the problem of motion recovery from image-shading variations for a configuration common in many undersea applications. On the basis of the image model developed earlier [J. Opt. Soc. Am. A 8, 217 (1991)], we show that the motion of a vehicle can be determined in closed form by using three Lambertian planar surfaces as optical beacons. PMID- 1634967 TI - Keeping up with the PAC. PMID- 1634968 TI - Classification and treatment of zygomatic fractures: a review of 1,025 cases. AB - The treatment of zygomatic fractures varies among surgeons, and the cosmetic and functional results are frequently less than optimal. A treatment guideline based on a simple classification of zygomatic fractures is presented. The emphasis is placed on the indications for closed and open reduction, consistent methods of three-dimensional alignment and fixation, and the management of concomitant infraorbital rim and orbital floor fractures. Postoperative results with regard to infraorbital nerve and maxillary sinus dysfunction, malar asymmetry, and orbital complications in the treatment of 1,025 consecutive zygomatic fractures are presented. PMID- 1634969 TI - The effects of zygomatic complex fracture on masseteric muscle force. AB - The masseter muscle often has been implicated as a primary cause of postreduction displacement of the fractured zygomatic complex. However, this contention has never been proved. This study compared masseter muscle force in 10 male controls with that in 10 male patients who had sustained unilateral zygomaticomaxillary complex (ZMC) fractures. Calculation of muscle force was based on measured bite force, electromyogram, and radiographic determination of muscle vectors. It was found that the masseter muscle in patients with ZMC fractures developed significantly less force than masseter muscle in controls. Following fracture, the masseter force slowly increased, but at 4 weeks following surgery the majority of patients were still well below control levels. The results of this study cast uncertainty on the role of the masseter muscle in postreduction displacement of the fractured ZMC. PMID- 1634970 TI - Current concepts in the surgical management of traumatic auricular hematoma. AB - There has been considerable confusion in the literature regarding the proper treatment of auricular hematoma. This has stemmed from an inadequate understanding of the mechanisms involved in the formation and propagation of this condition. This article reviews the literature and give suggestions as to the proper surgical management of this problem. PMID- 1634971 TI - Donor site morbidity of greater auricular nerve graft harvesting. AB - To better understand the risks of obtaining greater auricular nerve (GAN) grafts, a retrospective analysis of 29 patients who underwent GAN graft procurement between 1985 and 1990 was conducted. No short-term morbidity was noted. Thirteen patients developed symptomatic nerve injuries, of which 6 reported spontaneous resolution in an average of 4.6 months. Three patients developed neuromas and 1 formed a hypertrophic scar. Persistent nerve injury symptoms were well tolerated in all but one patient, who developed sympathetic-mediated pain. PMID- 1634972 TI - Maxillofacial esthetics: anthropometrics of the maxillofacial region. AB - Many artists, orthodontists, and surgeons have proposed guidelines for esthetic facial evaluation, but few have shown a scientific basis for their criteria. Farkas, however, made a substantial contribution to anthropometric facial measurements of adult whites. His raw data were used to develop a comprehensive set of ratios to define the esthetic face. A systematic maxillofacial evaluation derived from Farkas's data is presented, along with a brief description of its clinical application. PMID- 1634973 TI - Pseudocysts of the mandibular condyle. AB - The panoramic radiographs of 507 consecutive patients receiving comprehensive dental treatment were evaluated for the presence of radiolucencies in the mandibular condyles. Nine patients met the study criteria. Five patients had bilateral and four patients had unilateral circumscribed radiolucencies in the anterior aspect of the condyle. Computerized tomography confirmed that these radiolucencies were age-related anatomic variants that were accentuated and distorted during panoramic radiography. PMID- 1634974 TI - Incidence of temporomandibular joint symptoms following whiplash injury. AB - Recently there has been considerable litigation involving the development of temporomandibular joint (TMJ) pain and dysfunction following cervical musculoskeletal injury (whiplash). The purpose of this investigation was to interview, examine, and follow up patients with a diagnosis of whiplash injury to determine the incidence of associated temporomandibular disorders. Patients were divided into two categories: those with and those without radiologic evidence of cervical skeletal injury. In the 63 patients with radiographic evidence of cervical skeletal injury (group 1), none had clicking at the time of initial examination. In the 92 patients without positive radiographs (group 2), only one had clicking. At 1 month follow-up by telephone, 2 of 51 available patients in group 1 had developed clicking, but no new TMJ symptoms were reported by the 78 patients in group 2 contacted by phone. Seventy percent of the initial follow-up group (44 patients) with radiographic evidence of injury were contacted by telephone at 1 year and none reported new symptoms of TMJ pain or clicking. Sixty five percent of the initial follow-up group without radiographic evidence of injury (60 patients) were interviewed and also reported no new TMJ symptoms. These data indicate that the incidence of TMJ pain and clicking following whiplash injury is extremely low, and that patients who do not have clicking on resolution of their initial pain/dysfunction subsequently do not develop this problem. PMID- 1634975 TI - Role of osteopromotion in experimental bone grafting to the skull: a study in adult rats using a membrane technique. AB - This study explores the effect of an osteopromotive membrane technique in a mature animal model on the survival of membranous and endochondral bone inlays in mandibular defects and membranous bone onlays on the calvarial roof. Twenty-eight adult male rats received fibular or mandibular inlay bone grafts to trephine defects in the mandibular angle, as well as mandibular disc onlay grafts to the parietal and frontal bone regions. The results were assessed by gross inspection and light microscopy after 12 weeks. Membrane use markedly promoted bone deposition in the defects. The membranous bone inlays showed complete incorporation to the margins of the defect, whereas the endochondral grafts at all times were covered by a thin fibrous capsule and failed to incorporate. Onlay grafts generally resorbed substantially, but the grafts covered by a membrane seemed more active, developed an increased cancellous component, and showed less pronounced volumetric loss. The findings confirm the fact that a biological difference exists between membranous and endochondral bone. They also confirm the osteopromotive effect of the membrane technique, and suggest that the amount of bone needed for transplantation can be reduced using this method. PMID- 1634976 TI - Effect of ibuprofen on the healing and remodeling of bone and articular cartilage in the rabbit temporomandibular joint. AB - The purpose of this study was to determine the effect of ibuprofen on the healing and remodeling of bone and cartilage in the temporomandibular joint of the rabbit. Forty-two rabbits were operated on to create a groove and a hole in the articular surface of both the right and left mandibular condyles. Following surgery, the animals were divided into three groups. Group A (12 rabbits) was used as a control and the animals did not receive any medication. Group B (15 rabbits) was given a daily dose of 17 mg/kg of ibuprofen. Group C (15 rabbits) was given a daily dose of 34 mg/kg of ibuprofen. All animals were killed after 4 weeks. The 84 condyles were examined clinically and histologically. Statistical analysis showed a highly significant difference in the healing of bone and cartilage between groups A and C (P less than .01) and a significant difference between groups A and B (P less than .05). The results of this study indicate that ibuprofen has an adverse effect on the healing of bone and cartilage in the temporomandibular joint of the rabbit. PMID- 1634977 TI - Growth of a costochondral graft in the rat temporomandibular joint. AB - The aim of this study was to examine the growth and adaptation of costochondral grafts in the temporomandibular joint (TMJ). An autogenous rib section with either a short, intermediate, or long cartilaginous end was transplanted to replace the right mandibular condyle in 20-day-old rats. At 40 days, the mandibular halves with the short cartilage transplants were shorter than the contralateral halves, whereas the two sides did not differ in length in the rats with the intermediate transplant. The mandibular halves with the longest cartilaginous transplants initially were longer than the contralateral ones. The glenoid fossa was located more laterally as compared with the unoperated side. The results provide evidence that costochondral transplants do not adapt to the functional conditions of the TMJ and that the amount of cartilage in the graft has some bearing on its growth capacity. PMID- 1634978 TI - Creation of disc displacement in human temporomandibular joint autopsy specimens. AB - The purpose of this study was to investigate the possibility of iatrogenically creating disc displacement in the human temporomandibular joint (TMJ). Fourteen fresh TMJ autopsy specimens with superior disc position were selected for the study. The upper and lower joint spaces were exposed via a preauricular incision and two to three superficial mediolateral incisions were made in the inferior surface of the posterior disc attachment (ie, retrodiscal tissue). After these incisions were made it was possible to manually displace the disc anteriorly. To maintain the disc in the anterior position the condyle was positioned against the posterior disc attachment in a manner corresponding to the closed mouth position. The joints were then fixed in this relationship and magnetic resonance imaging (MRI) was repeated using the same scanning plane and scanning parameters as before intervention. After imaging, the joints were cryosectioned to show the degree of disc displacement. Histologic analysis was made of the posterior disc attachment. Postoperative MR images and cryosections showed the disc to be displaced anteriorly in 12 of the 14 joints. Displacement of the disc was complete in eight joints (the entire mediolateral dimension of the joint) and partial (only in the lateral part of the joint) in four joints. The disc remained in a superior position in two joints. Cryosections and histologic analysis showed the incisions in the inferior aspect of the posterior disc attachment to be superficial. The results of this study suggest that the integrity of the inferior aspect of the posterior attachment of the disc to the condyle is essential for keeping the disc in its position superior to the condyle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634979 TI - The prevention and treatment of aspiration of vomitus during pharmacosedation and general anesthesia. AB - The aspiration of gastric contents can occur in patients with a depressed level of consciousness. Pulmonary aspiration is a serious potential complication of pharmacosedation and general anesthesia. Sequelae associated with aspiration include pulmonary obstruction, chemical pneumonitis, secondary infection, and possibly death. Morbidity following aspiration is enhanced with an increased volume of aspirate, a more acidic pH, a high particle content, and bacterial contamination. Treatment of aspiration is dependent on the nature of the aspirate. Identifying aspiration-susceptible patients, employing preventive measures, and using careful anesthetic technique can effectively reduce the risk of aspiration. PMID- 1634980 TI - Keeping one in the air: iconography of the newly extracted tooth. AB - Tooth extraction remains a universally identifiable symbol of dentistry. Descriptions of the procedure in art and literature suggest three attributes of the dentist in the act of removing teeth: skill, power, and healing. Elements of the dentist's cultural identity are examined in light of the abundant imagery of dental extractions. PMID- 1634981 TI - Osteochondroma of the mandibular condyle: case report and review of the literature. PMID- 1634982 TI - Use of silicone drains in the management of cervicofacial infections. PMID- 1634983 TI - Difference of opinion or motivation? PMID- 1634984 TI - Bigger isn't always better. PMID- 1634985 TI - Bruce N. Epker to receive William J. Gies Award. PMID- 1634986 TI - AAOMS (American Association of Oral and Maxillofacial Surgeons) 74th annual meeting and scientific sessions. Honolulu, September 14-19, 1992. Abstracts. PMID- 1634987 TI - [Effects of inner ear immune responses on auditory function in guinea pigs]. AB - Following direct challenge with KLH antigen primary or secondary (after systemic immunization) to the ES (endolymphatic sac) in guinea pigs, ECoG (electrocochleograms) were recorded from the round window induced by click and tone pips. The recordings were carried out on the 2nd, 7th and 21st days after local antigen challenge. There were no abnormal findings in the ECoG of the primary antigen challenged animals. On the other hand, prolongation of latencies, decrease in amplitudes of APs (compound action potentials) and increases in SP/AP ratios were observed in the 2nd day recordings of the secondary antigen challenged animals. However, all parameters of ECoG in the 7th day recordings were normal. Decreases in AP amplitudes were again found in the 21st day recordings. The ECoG findings with click and tone pip stimulation showed similar results. From these findings, in conjunction with morphological observations, it is speculated that these ECoG findings are caused by immuno-injury to the ES and cochlea, as well as the resultant endolymphatic hydrops which develops acutely and gradually subsides after secondary challenge. PMID- 1634988 TI - [Image analysis of the inner ear with CT and MR imaging: pre-operative assessment for cochlear implant surgery]. AB - Recent progress in magnetic resonance imaging (MRI) has made it possible to obtain detailed images of the inner ear by delineating the lymphatic fluid within the labyrinth. We analyzed CT scans and MR images in 70 ears manifesting profound deafness owing to inner ear lesions and compared their detective ability for inner ear lesions. The following results were obtained. 1) CT scan examination showed slight to extensive ossification of the labyrinth in six ears (9%), whereas MRI examination revealed low to absent signal intensity of the inner ear in nine ears (13%). Therefore, it was concluded that MRI is more sensitive in detecting abnormalities of the inner ear than CT scan. 2) MRI provided useful information as to whether the cochlear turn is filled with lymphatic fluid or obstructed. This point was one of the greatest advantages of MRI over CT scan. 3) Abnormal findings in either or both the CT scan and the MRI were detected in suppurative labyrinthitis occurring secondary to chronic otitis media, bacterial meningitis and in inner ear trauma. However, such abnormal findings were not detected in patients with idiopathic progressive sensorineural hearing loss, ototoxicity or sudden deafness. These findings should be taken into consideration in pre-operative assessment of cochlear implant candidates. PMID- 1634989 TI - [Histological study of human lingual tonsil, especially changes with aging]. AB - The lingual tonsils, in company with the pharyngeal and palatine tonsils, constitute Waldyer's tonsillar ring and function as an immunological organ. However, fewer reports have been published on the lingual tonsil than on the other tonsils. It can hardly be said that changes is the lingual tonsil related to age have been studied in detail. The author reported a qualitative study on both gross and histological findings of the lingual tonsil, focusing on its changes with aging, in 204 autopsied cases (124 males and 60 females). The results of the qualitative observations obtained were as follows: 1. The lingual tonsils were classified into three shapes based on gross findings; flat, prominent and hypertrophic. Most of the hypertrophic tonsils were seen in the group in the 2nd decade and in those aged between the 4th and 6th decade of life. 2. Lymphatic tissues were classified into three types; isolated diffuse, adhesive converged and independent converged types. It was presumed that reconstruction of the lymphatic tissue should occur independently of proliferation of the connective tissue since the lymphatic tissues of the three were not related to aging. 3. Hyperplasia of the connective tissue, which separated the lymphatic tissues, started in the 2nd decade and rapidly increased after the 6th decade. Hyperplasia of the elastic fiber in the capsula also started in the 2nd decade and increased with aging. The results of quantitative observation were as follows: 1. Total area of the lingual tonsil and lymphatic tissues in each slice of the specimen showed two peaks in size in the 2nd and 5th decades. 2. Total sum of the lymphfolliculus had changed with aging in the same manner as mentioned above in "1". The ratios of the lymphfolliculus to the parenchymal tissue and to the lymphepithelial symbiosis had also altered with aging. However, the number of lymphfolliculi per unit was almost constant. A significant difference between the sexes was detected below the 4th decade, when hormonal sexual difference were manifest. 3. Total sum of the area of the crypt increased from the 4th decade onward. From these findings, it is concluded that the lingual tonsil transiently responds to aging from the first to the 2nd decade, when the pharyngeal and palatine tonsils have dominant functions, and becomes active from the 4th to 5th decades, followed by a decrease in function after the 6th decade though its activity persists in elderly individuals. PMID- 1634990 TI - [CT rim effects in various head and neck lesions]. AB - The authors evaluated various head and neck lesions seen from April 1988 through March 1990 both by plain and enhanced CT, examined the incidence of rim effect (or rim enhancement), classified these effects, and discussed underlying mechanisms. Materials consisted of 177 cases including primary tumors (28 benign and 49 malignant cases) and lymphadenopathy associated with malignancy (9 cases, metastatic nodes and malignant lymphomas), inflammatory lesions (20 cases), cystic lesions (12 cases), other lesions (7 cases, jugular thrombosis, carotid atheroma and aural lesions), and 22 cases without abnormal findings. Among the 177 cases, rim effects were observed in 22 cases (12%). These effects were analyzed and classified. The incidences of rim effect according lesion type are as follows; cervical lymphadenopathy associated with malignancy 5/9 (56%), primary tumors 8/77 (10%), inflammatory lesions none, cystic lesions 7/12 (58%), and others 3/7 (43%). The highest incidence was seen with cystic lesions including mucoceles of the paranasal sinuses and cervical cysts. Rim effects were classified as follows; Type 1: cystic pattern, Type 2: parenchymatous pattern, Type 3: vascular pattern and Type 4: others. Type 1 was seen in 15 cases (68%), Type 2 in 3 cases (14%), Type 3 in 3 cases (14%), and Type 4 in 1 case (5%). Type 1 included 6 cystic lesions, 3 malignant lymphadenopathies, 3 benign tumors and others. Type 2 included 2 malignant lymphadenopathies and 1 benign tumor, and Type 3, 2 jugular thromboses and 1 carotid atheroma. There was only one Type 4, a cystic lesion. Of interest is the mode of incidences among cervical lymphadenopathies associated with malignancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634991 TI - [Respiratory function in patients with perennial nasal allergy and pollinosis]. AB - There are many patients with allergic rhinitis who have no lower airway symptoms. The question arises as to whether or not the lower airway is involved in such cases, but the results of investigations in this field remain controversial. To answer this question, I performed various respiratory function tests in patients with perennial nasal allergy or pollinosis with or without a history of bronchial asthma. In addition, physiological changes in lower airway lesions were evaluated after challenge with antigen and histamine in these patients. In the present study, respiratory function was examined by autospirometry and the following results were obtained. 1. The group with perennial nasal allergy and a history of bronchial asthma showed significantly lower FEV1.0%, PER, %VC, V75, V50, and V25 values than the group with perennial nasal allergy without history of bronchial asthma, indicating an obstructive lesion in the lower airway. The group with perennial nasal allergy alone showed lower V75, V50, and V25 values than the control group, suggesting small airway obstruction. 2. The group with perennial nasal allergy and a history of bronchial asthma showed marked hypersensitivity in the lower airway after histamine inhalation. The group with perennial nasal allergy alone showed marked changes in V75, V50, and V25: the degree was between that of the control group and that in the group with a history of asthma. 3. In patients with pollinosis, various respiratory function tests showed no abnormalities during the in-season of pollinosis and the out-seasons. However, inhalation of antigen or histamine decreased various parameters, significantly V50 and V25, during the symptomatic season.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1634992 TI - [A temporal bone study of the jugular fossa]. AB - This study was performed to elucidate the anatomic variations of the jugular fossa (JF) on the basis of examination of 120 human temporal bones. Observations were made of temporal bones sectioned along a plane including the cochlea, the JF, and long axis of the internal auditory canal. The position of the upper margin of the JF was classified according to its relation to the tympanic cavity, the cochlea, and the internal auditory canal. The height of the upper margin of the JF was classified as follows. Low type; inferior to the level of the external auditory canal. Middle type; between the level of the external auditory canal and the cochlea. High type; superior to the level of the cochlea. The results revealed that 58 ears were of low type, 46 middle type, and 16 high type. Middle and high type comprised 62 ears, thus in 52% of ears the upper margin of the JF was situated superior to the external auditory canal. The relation between the JF and the cochlea was classified as follows. Medial type; medial to the medial margin of the cochlea. Lateral type; lateral to the medial margin of the cochlea. The results showed that 74 ears were of medial type, and 46 lateral type. Therefore, in 62% of ears the upper margin of the JF was situated medial to the medial margin of the cochlea. Forty-seven ears of medial type were of middle or high type. Ears of lateral type included none of high type. The jugular bulb diverticulum was observed in 32 ears, which consisted of 3 of low type, 13 middle type, 16 high type. When the upper margin of the JF was positioned higher, the JF was in a more medial position. However, no defect of the bony labyrinth was observed. In conclusion, it is considered that protrusion of the jugular bulb into the tympanic cavity was not caused by the abnormally high position of the JF, but by its lateral displacement. Distances from the JF to the surrounding structures were as follows; to the tympanic membrane 5.58 +/- 2.43mm (mean +/- S.D.), to the tympanic cavity 2.94 +/- 1.92mm, to the cochlea 4.93 +/- 2.20mm, and the internal auditory canal 5.82 +/- 2.38mm. PMID- 1634993 TI - [A case of transfusion-associated GVHD after total laryngectomy]. AB - We report a case of fatal transfusion-associated graft versus host disease (GVHD) that developed in a patient with laryngeal cancer. After a 39.6Gy irradiation dose, total laryngectomy with right radical neck dissection was performed. The postoperative course was uneventful. However, seven days after blood transfusion, high fever (38.5 degrees C) suddenly appeared. On the ninth day, watery diarrhea and facial erythema were observed. On the 12th day, liver disturbance and pancytopenia developed. The patient died on the 16th day because of overwhelming sepsis. Transfusion-associated GVHD has a mortality rate of more than 90%. Therefore, the most important procedure for preventing GVHD is the use of irradiated blood products. Furthermore unnecessary blood transfusion should be avoided. PMID- 1634994 TI - [Nasal airflow resistance before and after adenoidectomy]. AB - Nasal airflow resistance was measured in order to study physiological changes in the upper airway before and after adenoidectomy. The posterior method was better for measuring the state of the posterior portion of the nasal cavity, as compared with the anterior method. The posterior method was modified by improving the pressure piece, the size of which had been inadequate for insertion into a child's mouth. A positive correlation was found between the adenoidal nasopharyngeal ratio examined on X-ray film and the nasal airflow resistance both before and after surgery. Also there was a positive correlation between the weight of the resected adenoids and nasal airflow resistance preoperatively. Nasal airflow resistance was found to be significantly higher in patients who snored, breathed by mouth or had nocturnal breathing disorders than in those without these symptoms. PMID- 1634995 TI - The analysis of new short-period circadian rhythm mutants suggests features of D. melanogaster period gene function. AB - A number of new period gene (per) mutants were generated by in vitro mutagenesis and germ line transformation. Missense mutations were made at amino acid 589, which is altered in the 19 h short-period (per(s)) mutant, and insertion mutations were generated with peptides commonly used for epitope tagging. Most of these new per mutants had short behavioral rhythms. Flies with heteroallelic combinations of these new mutant per genes were found to have "hybrid" periods, i.e., they had values that were usually in between those of the individual alleles. These findings suggest that short-period per mutants are not unusual gain-of-function mutants but rather more traditional loss-of-function mutants that are unable to influence the circadian pacemaker in a proper manner. The data also suggest that the per protein may engage in important intermolecular interactions. PMID- 1634996 TI - Additive gene actions on the fiber number in the anterior optic tract of Drosophila melanogaster. AB - The influence of mutations in seven neurological genes on the number of fibers in the anterior optic tract (AOT) of Drosophila melanogaster has been investigated. It is shown that the number of fibers in the AOT can be drastically reduced in single and especially in multiple mutants. However, no evidence for synergistic interactions between the sample of mutations used in the sine oculis (so), reduced optic lobes (rol), minibrain (mnb), and small optic lobes (sol) genes was obtained at the level of the AOT. The rolKS222 and so mutations eliminate similar fiber sets in the AOT, which are distinctly different from those eliminated by solKS58 and mnb1. PMID- 1634997 TI - Mutants with delayed cell death of the ptilinal head muscles in Drosophila. AB - The emergence of adult Drosophila melanogaster from the puparium is followed by the programmed degeneration of a number of muscle groups. We have isolated two X linked mutants that delay the programmed death of at least some of these muscles. During eclosion, the fly makes use of a membranous sac, the ptilinum, which is later retracted into the head capsule. Six of the eight sets of muscles involved in the retraction then undergo degeneration. The muscle fibers initially show a gradual atrophy and then degenerate rapidly through fragmentation followed by absorption. In wild-type flies, this degeneration is obvious by 12 h after eclosion due to the loss of the birefringence of the muscles. Through mutagenesis with ethyl methanesulfonate, we isolated four mutants whose birefringence of the doomed muscles was retained even at 12 h. Mutants were genetically classified into two complementation groups; mcd-1 and mcd-2 (mcd: muscle cell death). The muscles of the mcd-1 mutants degenerate more slowly than that of the wild-type flies; the fibers enter the fragmentation step but are then not rapidly absorbed. In the mcd-2 mutants, the fibers atrophy more slowly than that in the wild-type flies and fail to undergo fragmentation. The difference in the process of the muscle death between the mcd-1 and the mcd-2 mutants suggests that at least two genes act on different steps in the process of muscle cell death. PMID- 1634998 TI - Genetic and age related models of neurodegeneration in mice: dystrophic axons. AB - Dystrophic axons (DA) are non-specific lesions that occur in a wide variety of human and animal diseases. In this paper we describe the distribution of these lesions in three newly discovered mouse neurological mutants. The distribution of DA in these mutants is defined by their names, lumbosacral neuroaxonal dystrophy (lnd), located on Chromosome 7, generalized neuroaxonal dystrophy (gnd) and vestibulomotor degeneration (vmd). The last mutant, which has degeneration as well as DA in lateral vestibular nucleus and vestibulo-spinal tracts, dies in the first weeks of life; the first two live for approximately one year. A previously described mutation, dystonia musculorum (dt), was found to produce generalized DA like gnd, but dt/dt mutants die at an early age. DA were also found to occur in the nuclei gracilis and cuneatus, in the area of Clark's column and in lumbo sacral spinal cord in aging normal mice either fed ad libitum or at a level of 40% dietary restriction. The dietary regimen had little effect on the numbers of DA observed in susceptible areas of the neuroaxis. The mutant models of neuroaxonal dystrophy may prove useful in studies of the pathophysiology of DA in general and of specific inherited diseases of man, such as infantile neuroaxonal dystrophy and Hallervordin-Spatz disease. PMID- 1634999 TI - Mutations on the second chromosome affecting the Drosophila eye. AB - In the developing eye of Drosophila, cell interactions appear to be responsible for organising undifferentiated cells into unit eyes, or ommatidia. Extensive mutagenesis has been used to search for mutations affecting the development and differentiation of ommatidia. These mutations have been characterized using sections of adults and immunocytochemistry of imaginal discs. Fourteen loci on the second chromosome are described that affect the spacing of the preclusters, the differentiation of ommatidial cells, orientation of the ommatidia, or architecture of the adult retina, that cause retinal degeneration in larval or pupal eye discs, or that cause homeotic transformation of part of the head. PMID- 1635000 TI - Pathology in the undergraduate medical curriculum. PMID- 1635001 TI - Immunocytochemical demonstration of IGF-II immunoreactivity in human phaeochromocytoma and extra-adrenal abdominal paraganglioma. AB - Insulin-like growth factor (IGF)-II immunoreactivity was demonstrated in 14 adrenal glands, six retroperitoneal paraganglia, 18 phaeochromocytomas, and six extra-adrenal abdominal paragangliomas through the use of a monoclonal antibody against rat IGF-II which cross-reacts with human IGF-II. A subpopulation of parenchymal cells in normal adrenal medulla and in retroperitoneal paraganglia was positively immunolabelled. Eighteen cases with phaeochromocytoma including two malignant and four multiple endocrine neoplasias all contained numerous IGF II-immunoreactive tumour cells. All six extra-adrenal abdominal paragangliomas contained numerous immunoreactive tumour cells. Almost all the other normal human adult tissues examined failed to immunolabel. These results indicate that IGF-II like immunoreactivity is widely expressed in normal and neoplastic human paraganglionic tissues, although its biological significance in these tissues has not been determined. PMID- 1635002 TI - Diagnosis of the acute ischaemic heart by ion elution from myocardium. AB - The post-mortem diagnosis of acute myocardial ischaemia may be difficult to establish in the absence of morphological changes in the myocardium or recent coronary thrombosis. Ischaemic cell injury leads to potassium (K) efflux and sodium (Na) influx and, if the blood is still circulating, the K:Na ratio of the tissue falls. In this study, the K:Na ratio was measured by eluting the ions from samples of myocardium and assaying the eluate. The method yields similar results to those obtained by a previous method, in which myocardial samples were homogenized. The K:Na ratios on samples of horizontal slices through the heart were plotted on maps of the slices. A low K:Na ratio corresponded to, but extended beyond, areas where there was morphological evidence of ischaemia. The method is simple and may be of use in routine practice. PMID- 1635003 TI - Renal cell carcinoma: comparison of morphological and flow cytometric parameters of primary tumour and invasive tumour lying within the renal vein. AB - Histological assessment and DNA flow cytometry have been performed on 15 kidneys containing primary adenocarcinomas which had invaded the renal vein. Comparison of morphological variables showed that samples of the intravenous tumour were more commonly composed of granular cells (53 per cent) than were samples from the main tumour mass (16 per cent), and were also of higher nuclear grade. In 7 of 14 kidneys, DNA studies showed either a higher S-phase fraction (five cases) or DNA aneuploidy (two cases) in tumour cells lying within the renal vein. The mean S phase fraction was also shown to increase in higher nuclear grades. Thus, both morphological and biological differences exist between invasive tumour cells lying within the renal vein and those in the main tumour. This is a useful model for the investigation of venous invasion and may give a better prediction of the metastatic potential of renal cell carcinoma. PMID- 1635004 TI - Myoendothelial contacts in arteriolosclerosis. AB - Human renal biopsies were examined electron microscopically to investigate close contacts between endothelial and smooth muscle cells in small arterioles. These myoendothelial contacts were seen in the form of cytoplasmic projections passing through fenestrae in the basal lamina. Most of these cell processes seem to arise from the endothelial cells. In the control vessels, the separation between the endothelial cells and smooth muscle cells of the tunica media is 0.09-0.27 microns. With arteriolosclerosis there is an increasing separation between the elements of the intima and the media, from 1.0 to 2.42 microns. In spite of this increasing separation, myoendothelial contacts maintain an intercellular space of 10-15 nm, as observed in the control vessels. At 2.42 microns of separation, the amount of extracellular material accumulated is such that the cells can no longer keep in contact. Break up of the myoendothelial contacts may be responsible for impairment of communication between the tunica intima and media in the vessel wall in arteriolosclerosis. PMID- 1635005 TI - Total parenteral nutrition for a terminally ill patient? PMID- 1635006 TI - Grief: re-forming life's story. PMID- 1635007 TI - Active metabolites of morphine. PMID- 1635008 TI - Use of the rectal, buccal, and sublingual narcotics in the management of cancer pain. PMID- 1635009 TI - Morphine intoxication during acute reversible renal insufficiency. PMID- 1635010 TI - Properties and function of the ocular melanin--a photobiophysical view. AB - This paper reviews the biosynthesis and physicochemical properties of the ocular melanin. Age-related changes of melanin granules and the corresponding formation of lipofuscin pigments in the retinal pigment epithelium (RPE) are also described. Adverse photoreactions of the eye and, in particular, light-induced damage to the RPE-retina are reviewed in relation to the ocular pigmentation. A hypothesis on the photoprotective role of the RPE melanin is presented that is based on the ability of the cellular melanin to bind redoxactive metal ions. Since bound-to-melanin metal ions are expected to be less damaging to the pigment cells, it is proposed that sequestration of heavy metal ions by the RPE melanin is an efficient detoxifying mechanism. It is postulated that oxidative degradation of RPE melanin may lower its metal-binding capability and decrease its anti-oxidant efficiency. Cellular and environmental factors that may contribute to possible oxidative damage of the RPE melanin are discussed in connection with the etiology of age-related macular degeneration. PMID- 1635011 TI - 212.8 nm laser photolysis of aromatic and aliphatic amino acids and related peptides. AB - The comparison of the photochemical properties of three aromatic and five aliphatic amino acids and three dipeptides was carried out using 212.8 nm laser irradiation and high performance liquid chromatography. The photochemical sensitivity, photolysis quantum yield and quantum yield of peptide bond scission were determined. Two-photon absorption coefficients of solvent (liquid water) and cell windows material (fused silica) at lambda = 212.8 nm were established. PMID- 1635012 TI - Intracellular localization of meso-tetraphenylporphine tetrasulphonate probed by time-resolved and microscopic fluorescence spectroscopy. AB - The effects of solvent pH on spectral properties and fluorescence decay kinetics were investigated in order to characterize the microenvironment of meso tetraphenylporphine tetrasulphonate (TPPS4) taken up by cells. Steady-state absorption and fluorescence spectra of TPPS4 in buffer solutions of different pH were used to identify a ring protonated species at pH less than or equal to 4. This dictation could also be distinguished from the unprotonated form by its altered fluorescence decay time (3.5 vs. 11.4 ns). In addition, time-resolved spectroscopy gave some evidence of a monocationic species existing at pH 6-9. This was concluded from the occurrence of another component with a decay time of 5 ns. Measurements of the spectral and kinetic properties of the fluorescence emission of single epithelial cells (RR1022) incubated with TPPS4 indicated that the sensitizer was mainly localized in a microenvironment with a pH of 5, a value which occurs intracellularly only within lysosomes. Cells kept in the dark exhibited the characteristic spectra of both the dication and the neutral form. The fluorescence decay showed two components with decay times of 2.6 ns and 10.6 ns. Irradiation of the cells changed the decay times to 4.6 ns and 13.4 ns and the dication fluorescence emission peak vanished, which is in accordance with the results obtained from buffer solutions at pH greater than or equal to 6. Therefore, we deduce that the photodynamic action leads to a rupture of the lysosomes and that the sensitizer is released into the surrounding cytoplasm. PMID- 1635013 TI - Phage T7 in biological UV dose measurement. AB - An experimental method complete with theoretical considerations is presented for the measurement of different biological UV doses. The method is based on the high sensitivity of phage T7 activity to UV light. A precisely determined T7 inactivation action spectrum is presented over a wide optical range (240-514 nm). Using the T7 spectral sensitivity in relation to the minimal erythema dose (MED) and the effective spectral irradiance from solar radiation for the MED, an example is given to determine the MED value based on the measurement of T7 inactivation for a given case. The advantages and applicability of the method are discussed. PMID- 1635014 TI - Photophysical processes in the NADH-alcohol dehydrogenase complex. AB - Fluorescent analysis showed the high sensitivity of the NADH-alcohol dehydrogenase complex to UV irradiation. The complex reacts to UV illumination with "photoresponse," a rapid decrease in NADH fluorescence intensity to some stationary level. No such decrease was found in the NADH solution without the protein. The maximum rate of photoresponse was observed at pH 8.0, i.e, the biochemical optimum for the enzyme. It is suggested that the main reason for the photoresponse is desorption of NADH from the protein due to vibrational and conformational relaxation after photoexcitation. The data obtained point to the possibility of controlling "dark" enzymatic processes with light. PMID- 1635015 TI - Proposal of modified mechanisms for photodynamic therapy. PMID- 1635016 TI - Coevolution: a history of the macroevolutionary approach to studying host parasite associations. AB - The year 1991 marked 100 yr of coevolution research. I have reviewed the first 90 yr of this history. Three chronological phases are apparent: recognition of predictable associations among hosts and their parasites; search for patterns of association and their underlying causes, emphasizing either correlated biogeographic patterns or correlated phylogenies; and development of objective and repeatable methodologies for reconstructing and interpreting these patterns of association. Von Ihering, an outspoken anti-Darwinian, was undoubtedly the first to recognize and make use of predictable host-parasite associations. Kellogg and Fahrenholz, however, had more profound influence on subsequent generations, but in different directions. Kellogg attempted to meld natural selection with speciation by isolation. He also considered host specificity a component of coevolution, important but variable. His work laid the foundation for future research concentrated on biogeographic interpretations of host parasite relationships. This emphasis and Metcalf's failed attempts to provide adequate mechanisms for reconstructing phylogenies reduced the biogeographic approach to an empirical research program in the hands of Manter. Fahrenholz, on the other hand, exposed to a strong anti-Darwinian sentiment, emphasized the importance of strict host specificity. This led to Eichler's formulation of the first 3 coevolutionary rules and the conclusion that host specificity was not a component but the cause of coevolution and ultimately the tautology inherent in the phylogenetic approach. All had to rely on 1 assumption, that host and parasite phylogenies were reflected in the taxonomic hierarchy. Hennig criticized this assumption and provided a method whereby phylogenies are reconstructed independently. Brooks melded this new phylogenetic method (cladistics) with an equally new biogeographic method (vicariance biogeography), providing the foundations for the modern macroevolutionary approach to studying host-parasite associations. PMID- 1635017 TI - Origins, diversification, and historical structure of the helminth fauna inhabiting neotropical freshwater stingrays (Potamotrygonidae). AB - Members of the freshwater stingray family Potamotrygonidae occur throughout the major river systems of eastern South America that empty into the Atlantic Ocean. Ichthyologists have tended to assume that the ancestor of the potamotrygonids was an Atlantic marine or euryhaline stingray that dispersed into freshwater, presumably during the last marine ingression 3-5 million years ago. The helminth parasites that inhabit potamotrygonids suggest an alternative perspective on their origin. Phylogenetic and biogeographic analysis of the helminths inhabiting potamotrygonids suggest that the hosts are derived from an ancestral Pacific urolophid stingray that was trapped in freshwater by the uplifting of the Andes beginning perhaps as early as the early Cretaceous period and ending by the mid Miocene epoch, changing the course of the Amazon River, which previously had flowed into the Pacific Ocean. PMID- 1635018 TI - Parasites as probes for biodiversity. AB - Cestodes of the genus Linstowia, parasitic in marsupials, show patterns of coevolution and ancient historical-ecological connections. Correlated with the breakup of the austral landmasses (Gondwanaland) of the Neotropical and Australian regions from the Antarctic continent, the age of this host-parasite community is estimated to be between 60 and 70 million years old. Based on the data from the survey of parasites of mammals from throughout Bolivia and from the phylogenetic analysis of the cestodes, we urge the planners of biodiversity preserves in the neotropics to consider the Yungas of Bolivia as a region that supports an ancient ecological community worthy of consideration as a biopreserve. PMID- 1635019 TI - Congruent and synchronic patterns in biogeography and speciation among seabirds, pinnipeds, and cestodes. AB - Congruence in biogeographic patterns among diverse assemblages of taxa indicates uniformity in the historical determinants of biotic distributions. Comparisons of host and parasite phylogenies and the elucidation of distributional area relationships are requisite components of analyses in historical biogeography. Host-parasite associations with broad geographic ranges are often archaic and have been structured largely by coevolutionary processes. In contrast, the origins and radiation of the primary cestode faunas of some seabirds (Alcataenia spp./Alcidae) and pinnipeds (Anophryocephalus spp./Phocidae and Otariidae) are associated with colonization. These young colonizing faunas, in the Holarctic Region, were influenced by a common history during the late Pliocene and Pleistocene epochs. Periodic range contraction, with isolation in refugial centers, and subsequent expansion into postglacial habitats for hosts and parasites coincided with the cyclic pattern of stadials and interstadials. During the past 2-3 million years following colonization, these dramatic climatic fluctuations strongly influenced the continuity of ecological associations in marine habitats and appear to have been the determinants of congruent and synchronic patterns of speciation among these disparate taxa of marine homeotherms and eucestodes. PMID- 1635020 TI - A phylogenetic and biogeographic analysis of the genera of Spirorchinae (Digenea: Spirorchidae) parasitic in freshwater turtles. AB - Cladistic analysis of the freshwater genera of Spirorchinae (Schistosomatoidea: Spirorchidae sensu Yamaguti, 1971) plus Haematotrema Stunkard, 1923, and Aphanospirorchis Platt, 1990, was completed. The Spirorchinae were considered monophyletic based on synapomorphies of the esophagus. Three lineages, Spirhapalum (Europe/Asia), Plasmiorchis+Hemiorchis (India), and Spirorchis + Henotosoma + Haematotrema + Aphanospirorchis (North America), were identified. Nelsen consensus analysis was used as the basis for recognizing 3 valid monophyletic genera: Spirhapalum, Plasmiorchis, and Spirorchis. Hapalotrematinae sensu Smith, 1972 (e.g., Hapalorhynchus/Coeuritrema), is considered the most plesiomorphic group of spirorchids. Freshwater representatives of the hapalotrematines have been reported from 7 of 12 extant turtle families, including the relatively primitive Pelomedusidae (Pleurodira) and exhibit a worldwide distribution. It is hypothesized that this group arose in the early Triassic period, prior to the breakup of Pangea. Thus, it represents a primitive lineage that was present during the diversification of turtle lineages in the mid Mesozoic era. Spirorchinae arose later (late Cretaceous period) as a Laurasian component parasitic in the more recent pond turtles (Emydidae + Bataguridae). Species of Spirhapalum retained a relatively plesiomorphic distribution, and they are found in emydids (Europe) and batagurids (Asia). Species of Spirorchis arose and diversified with North America emydids following the separation of North America and Europe in the late Cretaceous or early Tertiary periods. Species of Plasmiorchis are hypothesized to be derived from Asian ancestors that accompanied the colonization of India by Asian batagurids during the early Tertiary period. The presence of Spirorchis species in snapping turtles (Chelydridae/North America) and of Plasmiorchis species in Indian soft-shelled turtle (Trionychidae) are considered independent colonization events. PMID- 1635021 TI - The roles of ecological and evolutionary influences in providing structure to parasite species assemblages. AB - Parasite species assemblages currently are thought to range from isolationist to interactive, their dynamic properties being related to the number of species and types of hosts involved. The literature contains few experimental tests of this concept, however, and many of the host/parasite systems studied to date are not amenable to experimental manipulation. In this review, the presence of a parasite species, in a sample of host individuals, is considered to be an evolutionary phenomenon, but the parasite's population structure is considered to be an ecological one. Studies that allow evaluation of these 2 influences are comparative in nature and include data from a series of homogeneous samples of host populations. A lottery model is presented, in which hosts acquire their assemblages of parasites by Monte Carlo type sampling from multiple kind arrays; the major structuring influence is the relative probability of becoming infected by various parasite species. Claims of parasite species interaction need to be supported by studies showing departures from the predictions of this model. The species density and infraassemblage diversity index distributions are recommended as quantitative tools useful in such work. PMID- 1635022 TI - Allozyme analysis of Trichinella isolates from various host species and geographical regions. AB - Allozyme analysis was carried out on 152 Trichinella isolates from synanthropic and wild animals and from humans; the isolates were collected from 5 continents. The analysis, involving 27 enzymes, revealed the presence of 8 distinct gene pools, termed T1-T8. Four of the genetic groups represent the 4 previously proposed species: Trichinella spiralis sensu stricto (T1), Trichinella nativa (T2), Trichinella nelsoni (T7), and Trichinella pseudospiralis (T4). The other 4, T3, T5, T6, and T8 are distinct from previously described species. The absence of allozymic hybrid patterns among even sympatric groups indicates a lack of gene flow among the groups. Principal component analysis and the unweighted pair group method of analysis were used to assemble allozyme patterns of the 152 isolates into discrete groups and to show their relative relationships. Both analyses indicated the presence of 8 primary clusters that correlated with the gene pools revealed by direct allozyme profile analysis. The absence of evidence of gene flow among the gene pools and the high level of allozymic differentiation between the cluster groups support the concept that the genus Trichinella is composed of several sibling species. PMID- 1635023 TI - Biological characterization of Trichinella isolates from various host species and geographical regions. AB - Forty isolates of Trichinella collected from 5 continents were compared for 7 biological characters: newborn larvae produced per female worm cultured in vitro at the seventh, eighth, and ninth day postinfection, host muscle nurse cell development time, reproductive capacity index in rats and chickens, and resistance of muscle larvae to freezing. The isolates also were compared by analyses of an environmental character of the location from which they were isolated: the isotherms for January and July. By factorial analysis of correspondence of the biological and environmental data, the 40 isolates were grouped into 8 gene pools (T1-T8). The environmental temperature-related distribution was more evident for the sylvatic isolates (T2, T3, T5, T6, T7, T8), than for T1, which was isolated from domestic pigs, and for T4, a bird-adapted, nonencapsulating genetic type. The 8 biological groups correlated closely with the 8 gene pools previously identified on the basis of allozyme analysis. These results support the concept that the genus Trichinella is composed of at least 5 distinct gene pools or sibling species: Trichinella spiralis sensu stricto (T1), Trichinella nativa (T2), Trichinella sp. (T3), Trichinella pseudospiralis (T4), and Trichinella nelsoni (T7), and 3 other groups of uncertain taxonomic status (i.e., T5, T6, and T8). PMID- 1635024 TI - Taxonomic revision of the genus Trichinella. AB - The analysis of genetic, biochemical, and biological data on about 300 Trichinella isolates, reported in the literature, allows a taxonomic revision of this genus. We propose the recognition of 5 sibling species, Trichinella spiralis (Owen, 1835) sensu stricto; Trichinella nativa Britov and Boev, 1972; Trichinella pseudospiralis Garkavi, 1972; Trichinella nelsoni Britov and Boev, 1972 sensu stricto; and Trichinella britovi n. sp., on the basis of biochemical and biological characteristics. Trichinella britovi n. sp. is characterized by distribution in the Palaearctic Region; newborn larvae (NBL) production in vitro of 35-55 NBL/72 hr; nurse cell development time (NC d.t.) between 24 and 42 days postinfection (d.p.i.); low reproductive capacity index (RCI) in mice, rats, and pigs; low resistance to freezing; 1 unique marker allozyme; and moderate pathogenicity for humans. The new species is most similar to Trichinella nativa but differs from it in 4 allozymes, in having less resistance to freezing, in having a different pattern of major ribosomal DNA fragments after endonuclease digestion, and in distribution area. Trichinella nativa is characterized by a holarctic distribution; hosts that are sylvatic mammals; NBL production in vitro 28-54/72 hr; NC d.t. between 20 and 30 d.p.i.; low RCI in mice, rats, and pigs; high resistance to freezing; 2 unique marker allozymes; and moderate to severe pathogenicity for humans. Trichinella spiralis sensu stricto is characterized by a cosmopolitan distribution in domestic pigs, associated wildlife, and humans; high NBL production in vitro (greater than 90 NBL/72 hr); NC d.t. between 16 and 37 d.p.i.; high RCI in mice, rats, and pigs; no resistance to freezing; 6 unique marker allozymes; and high pathogenicity for humans.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635025 TI - Cyclophilin of Schistosoma japonicum. AB - A 623-bp cDNA molecule encoding cyclophilin, a specific cyclosporin A-binding protein, has been isolated from Schistosoma japonicum using a heterologous cDNA probe from Echinococcus granulosus. The nucleotide sequence of this molecule has been determined, and the deduced amino acid sequence has revealed extensive homology with homologues of other species. Southern blot analysis suggests that S. japonicum cyclophilin is the product of a single-copy gene. The cloning of this cDNA will allow an investigation of cyclophilin as a possible target of the antischistosome effects of cyclosporin A. PMID- 1635026 TI - Separation and characterization of adult worm proteins and glycoproteins from the liver fluke Opisthorchis viverrini. AB - Detailed studies of liver fluke proteins and antigens are necessary to facilitate further investigation of the human immune responses to these parasites. Accordingly, Opisthorchis viverrini antigens were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. We initially encountered excessive background smearing, vertical streaking, and indistinct bands that were similar to problems previously described by investigators studying this and other trematodes including Schistosoma mansoni. These problems were especially evident with silver staining of proteins and occurred despite the extensive use of protease inhibitors. They were minimized by using mini (vs. large) SDS-PAGE and Coomassie blue protein staining. With the latter 2 techniques, adult worm somatic proteins and excretory-secretory products were separated and characterized. Immunoblots using rabbit anti-adult worm sera demonstrated that some of these proteins were antigens common to both the adult and metacercarial stages. Several of these antigens also corresponded (according to molecular weight) to glycoproteins, detected by concanavalin A blotting. These findings form a base for subsequent studies of the human immune response to liver fluke infection. PMID- 1635027 TI - Detection of Schistosoma mansoni circulating cathodic antigen for evaluation of resistance induced by irradiated cercariae. AB - The appearance of serum levels of circulating cathodic antigen (CCA) detectable by a monoclonal antibody (mAb) (5H11) antigen-capture sandwich enzyme-linked immunosorbent assay (ELISA) system was evaluated during acute Schistosoma mansoni infections in female CF1 mice exposed to either 100 or 25 cercariae. Measurable CCA levels occurred in these groups at 5 and 7 wk after infection, respectively. The kinetics of appearance of CCA were thus related to the intensity of infection. The level of resistance developed by female C57BL/6 mice upon immunization with irradiated cercariae, as expressed by both worm burden and CCA levels after cercarial challenge was evaluated. Immunization conferred 44% protection against the challenge infection, and the level of CCA detected in the sera of the control group was significantly (P less than 0.02) higher than that found in the sera of the immunized group, 6 wk after challenge. These results demonstrate that CCA detection by the 5H11 mAb antigen-capture sandwich ELISA can reflect vaccine-induced resistance against S. mansoni. Localization studies showed that 5H11 reacts with a CCA epitope in the adult worm gut and to a lesser extent with the male tegument. Adaptations of this and other antigen detection systems may prove useful in monitoring the efficacy of developmental vaccines, an ability that may be essential for the extension of such studies to humans. PMID- 1635028 TI - Changes in humoral responses to Trypanosoma cruzi during the course of infection in mice held at elevated temperature. AB - A parasite-specific, enzyme-linked immunosorbent assay and immunoblot analysis were used to examine the development of humoral immunity in Trypanosoma cruzi infected C3H mice that survive acute infection when held at elevated environmental temperature. Both parasite-specific antibody levels and numbers of antigens identified increased during infection in mice held at 36 C, with the greatest reactivity measured in sera from mice that had resolved parasitemias. Heat shock of culture forms of T. cruzi resulted in production of different antigens, but there was no strong difference in the antigens recognized by sera from mice held at room temperature and those recognized by sera from mice held at 36 C. Immunoblot analysis using blood-form trypomastigote antigens identified a band of approximately 61 kDa produced by trypomastigotes in mice held at 36 C that was strongly detected by sera from mice held at 36 C. Little if any reactivity to this antigen was observed using sera from mice held at room temperature. PMID- 1635030 TI - Investigation of transplacental transmission of Caryospora bigenetica (Apicomplexa: Eimeriidae) in mice. AB - Five pairs of female Swiss-Webster mice were caged with 5 males (2 females/1 male). Eight females were inoculated orally with 2.6 x 10(5) Caryospora bigenetica oocysts either 3 days before mating, 3 days after mating (PMD), 9 PMD, or 16 PMD. The remaining 2 females were inoculated orally with Hanks' balanced salt solution and served as controls. One female from each cage delivered naturally at full term and the second female delivered by cesarean section on postmating day 18. The number of offspring per litter ranged from 7 to 12. One female produced a litter of 3 stillborn and 5 liveborn offspring. Seven of 8 female mice exhibited swollen muzzles and footpads 8 days after inoculation. Caryospora bigenetica was identified in tissues of muzzle, tongue, footpad, uterus, and placenta at necropsy. This is the first report of C. bigenetica in uterus and placenta. Clinical signs and tissue infections were not observed in control mice or in any offspring of the 10 female mice. This study presents evidence that C. bigenetica is not transmitted transplacentally. PMID- 1635029 TI - Binding of complement to trypomastigotes of a Brazil strain of Trypanosoma cruzi: evidence for heterogeneity within the strain. AB - Binding of the complement components C3 and C5 to epimastigote and trypomastigote stages of the Brazil strain of Trypanosoma cruzi was examined using radioligand binding and flow cytometric assays. Fibroblast-derived trypomastigotes bound approximately 40% fewer molecules of [125I]C3 per parasite than did epimastigotes. The predominant molecular species of C3 deposited on fibroblast derived trypomastigotes was the inactive form iC3b. Addition of parasite-specific antisera failed to enhance the number of molecules of [125I]C3 per parasite or the proportion of active to inactive C3b. Flow cytometric studies revealed that only 50% of trypomastigotes (fibroblast-derived or blood-form) bound C3. In contrast to results of the [125I]C3 binding studies, flow cytometric analysis showed that the percentage of trypomastigotes binding C3 actually increased upon incubation with parasite-specific antisera. C5 was found also to bind to only a percentage of trypomastigotes. PMID- 1635031 TI - A comparative study of the host-parasite relationship of Pomphorhynchus patagonicus (Acanthocephala) in two species of fish from Lake Rosario (Chubut, Argentina). AB - Some aspects of the host-parasite relationships of Pomphorhynchus patagonicus (Acanthocephala) in 2 fish species from Lake Rosario (Chubut, Argentina) were studied. The fish species Patagonina hatcheri (Atherinidae) is autochthonous, and Oncorhynchus mykiss (Salmonidae) is introduced. The host species appears to influence attachment, size, sexual maturity, and distribution of parasites along the digestive tract. In P. hatcheri, an effective major host, parasites are attached firmly to the wall of the gut, well developed, attain a greater size, and a large proportion of females is gravid with ripe eggs. In O. mykiss, an unsuccessful host, there were many unattached parasites that were small and not well developed; gravid females were rare and never had ripe eggs. PMID- 1635032 TI - Population dynamics of Plasmodium falciparum sporogony in laboratory-infected Anopheles gambiae. AB - The population dynamics of cultured Plasmodium falciparum parasites was examined during their sporogonic development in Anopheles gambiae mosquitoes. Estimates of absolute densities were determined for each life stage, and life tables were constructed for each of 38 experimental infections. Macrogametocyte and ookinete mortalities contributed equally to the overall mortality. On average, there was a 40-fold decrease in parasite numbers in the transition from the macrogametocyte to the ookinete stage, a 69-fold decrease in the transition from ookinete to oocyst stages, and a total net decrease in parasite numbers from macrogametocyte to oocyst stage of 2,754-fold (i.e., multiplicative). There was no relationship between macrogametocyte and ookinete densities due to the inherent variability in fertility among different gametocyte cultures. There was a curvilinear relationship (r2 = 0.66) between ookinete and oocyst densities. Above a threshold of about 30 ookinetes/mosquito, the oocyst yield per ookinete became increasingly greater with increasing ookinete density. There was a linear relationship (r2 = 0.73) between oocyst and sporozoite densities, with an average of 663 salivary gland sporozoites produced per oocyst. Sporozoite production per oocyst was not affected by oocyst density and virtually all oocyst infections resulted in sporozoite infections of the salivery glands. This quantitative study indicates that the sporogony of cultured P. falciparum in laboratory-infected A. gambiae is an inefficient process and that the ookinete is the key transitional stage affecting the probability of vector infectivity. PMID- 1635033 TI - Histochemistry and ultrastructure of the metacercarial cyst of Bolbogonotylus corkumi (Trematoda: Cryptogonimidae). AB - Histochemical and ultrastructural studies were conducted on the metacercarial cyst of the cryptogonimid trematode Bolbogonotylus corkumi from the muscle tissue of fantail darters Etheostoma flabellare. The metacercarial cyst consisted of an outer host capsule and an inner parasite cyst. The host capsule was composed of an outer region of fibroblasts, collagen, macrophages, and unidentified cells, and an inner region containing degenerating cells. The parasite cyst was thin, homogenous, and noncellular in nature. The host capsule stained strongly for connective tissue and proteins and moderately for lipids, nucleic acids, nonspecific esterase activity, and acid and alkaline phosphatase activities. The parasite cyst stained intensely for acid mucopolysaccharides and moderately for acid phosphatase activity. A thick glycocalyx occurred between the parasite cyst and metacercarial tegument. PMID- 1635034 TI - Occurrence of the acanthocephalan Eocollis arcanus in Georgia. AB - The geographical range of the acanthocephalan Eocollis arcanus Van Cleave, 1947, is extended to Atlantic drainages in Georgia where it occurs in a previously unreported host, the centrarchid Centrarchus macropterus. PMID- 1635035 TI - Influence of a menhaden oil diet on cercarial penetration of Schistosoma mansoni. AB - The ability of a menhaden oil (MO) diet to influence cercarial penetration into mouse tail skin was evaluated. Male CD-1 mice 4-6 wk old (15.2 g average weight) were fed a 0, 10%, or 20% MO-supplemented diet for 2 wk. After this time mice were infected with either 65 +/- 3 or 145 +/- 3 [35S]methionine/cysteine-labeled cercariae for 1 hr by tail immersion. Twenty-four hours and 7 days later groups of mice were killed and their tail skin removed and autoradiographed. At 24 hr postinfection, mice fed a 20% MO diet had significantly higher cercarial penetration than controls and 10% MO diets (56% +/- 5.2 vs. 44% +/- 2.9, P = 0.02, 1-tailed t-test). After 7 days mice fed a 20% MO diet retained more radioactive foci than controls or 10% MO diets (21% +/- 2.0 vs. 15% +/- 1.3, P = 0.01, 1-tailed t-test). PMID- 1635036 TI - Serologic response of the opossum Didelphis virginiana to a temperature-sensitive mutant (ts-4) of Toxoplasma gondii. AB - A study was designed to measure the Toxoplasma gondii-specific IgM and IgG antibody responses of opossums inoculated with tachyzoites of the temperature sensitive mutant of T. gondii, ts-4, and to examine its persistence in the tissues. Four young opossums seronegative for anti-Toxoplasma gondii IgM and IgG antibodies immediately after capture and 4 wk later were injected subcutaneously with 1.8 x 10(6) ts-4 tachyzoites; a fifth opossum (also seronegative) received an injection of saline only. Serum was collected weekly and titered by modified direct agglutination for anti-Toxoplasma gondii IgM and IgG. IgM titers were detectable from week 1 to week 6 postinoculation (PI). IgG was measurable by week 3 and remained high for 30 wk PI when the opossums were killed and examined. The control opossum did not develop a specific antibody response. At necropsy major lesions were not found. No anti-Toxoplasma gondii IgG was detected in serum collected from mice injected with tissues prepared from the opossums at necropsy, and no T. gondii was found on impression smears made at necropsy from these mice. Modified direct agglutination performed with or without 0.2 M 2-mercaptoethanol worked well for measuring specific IgM and IgG antibodies in experimentally infected opossums. PMID- 1635037 TI - In vitro oxygen consumption and motility of Cryptobia salmositica, Cryptobia bullocki, and Cryptobia catostomi (Sarcomastigophora: Kinetoplastida). AB - Cryptobia salmositica (pathogenic and vaccine strains), Cryptobia bullocki (pathogenic), and Cryptobia catostomi (nonpathogenic) have similar oxygen consumption rates (0.17 +/- 0.01 nm O2/10(6) parasites). Incubation with sodium azide (5 microliters of a 1-M solution to 1 ml of parasite suspension, i.e., a 5 mM final concentration) reduced the oxygen consumption by approximately 4.5-fold. Motility of the parasites was also greatly reduced in sodium azide. The oxygen consumption and motility of the parasites returned to preazide treatment levels when the azide was removed even after 24 hr of incubation in sodium azide. The activities of hexokinase, pyruvate kinase, and cytochrome C oxidase were not detected in the 3 species of Cryptobia. PMID- 1635038 TI - Theileria sergenti proliferates in SCID mice with bovine erythrocyte transfusion. AB - The unavailability of in vitro or in vivo experimental systems has been the major factor hampering the progress of research studies on Theileria sergenti, causative agent of theileriosis, a major disease of cattle in Japan. We report the first successful propagation of T. sergenti in SCID mice into which uninfected bovine erythrocytes (Bo-RBC) were supplied periodically. The infectivity of T. sergenti proliferated in an SCID mouse was ascertained by successful transfer of infection into another SCID mouse into which uninfected Bo RBC were supplied periodically. PMID- 1635039 TI - An introduction to the five-factor model and its applications. AB - The five-factor model of personality is a hierarchical organization of personality traits in terms of five basic dimensions: Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness to Experience. Research using both natural language adjectives and theoretically based personality questionnaires supports the comprehensiveness of the model and its applicability across observers and cultures. This article summarizes the history of the model and its supporting evidence; discusses conceptions of the nature of the factors; and outlines an agenda for theorizing about the origins and operation of the factors. We argue that the model should prove useful both for individual assessment and for the elucidation of a number of topics of interest to personality psychologists. PMID- 1635040 TI - The five-factor model: issues and applications. PMID- 1635041 TI - Editor's introduction to Tupes and Christal. PMID- 1635042 TI - Author's note on "Recurrent personality factors based on trait ratings". PMID- 1635043 TI - Recurrent personality factors based on trait ratings. AB - Intercorrelations among ratings on 35 personality traits, selected as representative of the personality domain, were obtained for eight samples. These samples differed in length of acquaintanceship from 3 days to more than a year; in kind of acquaintanceship from assessment programs in a military training course to a fraternity house situation; in type of subject from airmen with only a high-school education to male and female undergraduate students to first-year graduate students; and in type of rater from very naive persons to clinical psychologists and psychiatrists with years of experience in the evaluation of personality. Centroid or multiple-group factors were extracted and rotated orthogonally to simple structure. For one study, an independent solution was obtained in which analytic rotations were accomplished on an IBM 650 computer using Kaiser's normal varimax criterion. Five fairly strong and recurrent factors emerged from each analysis, labeled as (a) Surgency, (b) Agreeableness, (c) Dependability, (d) Emotional Stability, and (e) Culture. PMID- 1635044 TI - Assessing the five-factor model of personality description. AB - Several approaches to assessing the dimensions of the five-factor model are reviewed and evaluated. The items in the assessment instrument may be adjectives or phrases, and the instrument itself may have been developed specifically to measure the five factors or may have been reinterpreted in terms of the five factor model. Data are presented comparing an adjective-based measure of the model (Goldberg, 1990) with two phrase-based measures (Costa & McCrae, 1985; Hogan, 1986), and recommendations are made for the choice of an instrument in different research contexts. Allport's (1937) distinctions between the structure of the trait lexicon and the structure of personality in individuals are reiterated. PMID- 1635045 TI - Implicit personality theory and the five-factor model. AB - The Big Five have not only been identified in ratings of knowledgeable informants, but also in ratings of strangers, in co-occurrence likelihood ratings of traits, in semantic similarity ratings of trait pairs, and in prototypicality ratings of acts for traits. This article describes the shared and distinctive characteristics of correlations among trait ratings and implicit personality theory and reviews studies that compare the structure of memory-based ratings and of on-line behavior counts. Three hypotheses suggested in the literature to account for these correlations are delineated and discussed: an accurate reflection hypothesis, a distortion hypothesis, and an overlap hypothesis. It is concluded that the distortion hypothesis, has been discredited and that an overlap model best accounts for the available evidence. This implies that traits are real and accurately perceived, provided that the judges have the necessary information. PMID- 1635046 TI - The five-factor model in personality: a critical appraisal. AB - This critical appraisal aims to position the five-factor model within the multifaceted field of personality psychology by highlighting six important limitations of the model. These are the model's (a) inability to address core constructs of personality functioning beyond the level of traits; (b) limitations with respect to the prediction of specific behavior and the adequate description of persons' lives; (c) failure to provide compelling causal explanations for human behavior and experience; (d) disregard of the contextual and conditional nature of human experience; (e) failure to offer an attractive program for studying personality organization and integration; and (f) reliance on simple, noncontingent, and implicitly comparative statements about persons. The five factor model is essentially a "psychology of the stranger," providing information about persons that one would need to know when one knows nothing else about them. It is argued that because of inherent limitations, the Big Five may be viewed as one important model in personality studies but not the integrative model of personality. PMID- 1635047 TI - Personality and psychopathology: an application of the five-factor model. AB - Our review is concerned with the relationship of the five-factor model of personality to psychopathology, focusing in particular on Axis II personality disorders and depression. The five factors provide a particularly compelling model for interpreting the Axis II personality disorders as maladaptive variants of normal personality traits. However, we also discuss methodological and conceptual limitations of this application. There has been little research on the relationship of Openness, Agreeableness, and Conscientiousness to Axis I mental disorders, but considerable attention has been given to Neuroticism and Extraversion. We focus in particular on the difficulty in distinguishing between the various ways in which personality can relate to depression, either as a predisposition to, a complication of, a pathoplastic effect upon, or a spectrum variant of the mental disorder. We conclude with recommendations for future research. PMID- 1635048 TI - Personality and health: advantages and limitations of the five-factor model. AB - Interest in the association between personality characteristics and physical health has been renewed in recent years. Theory and research in this area has also been complicated by conceptual and methodological limitations. The present article briefly reviews this literature and discusses the advantages and limitations of the five-factor model of personality as an integrating framework for studies of personality and health. The model has already been fruitfully applied in several contexts, and more possibilities exist. Although it has some potential limitations, the application of the five-factor model--as well as other aspects of current personality theory and research--is likely to facilitate progress in the study of how personality influences health. PMID- 1635049 TI - Probing the big five in adolescence: personality and adjustment during a developmental transition. AB - The present study probed the links among Big Five personality differences, self reported personality differences, and adjustment to school among young adolescents. We used a multimethod converging analysis, with three sources of data: (a) adolescent self-report on standardized personality inventories; (b) classroom teacher trait ratings and evaluations of adjustment; and (c) school guidance counselor evaluations of adjustment. Evaluations of adolescent adjustment were systematically related to Big Five personality differences, as assessed by both classroom teachers' and school counselors' ratings. For classroom teachers, adjustment was closely related to evaluations on the Big Five dimension of Conscientiousness. Adolescent self-report on several standardized measures was not related to adult evaluation of school adjustment. We suggest that the five-factor model may be a useful tool for probing adjustment during the transition to adolescence. PMID- 1635050 TI - On traits and temperament: general and specific factors of emotional experience and their relation to the five-factor model. AB - In this article we investigate relations between general and specific measures of self-rated affect and markers of Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness. Replicating previous research, we found strong and pervasive associations between Neuroticism, its facets, and the various negative affects; and between Extraversion, its facets, and the positive affects. Conscientiousness also had a significant, independent relation with general positive affect, but this effect was entirely due to the specific affect of attentiveness, which was more strongly related to Conscientiousness than Extraversion. Conversely, only the achievement facet of Conscientiousness correlated broadly with the positive affects. Finally, hostility had a strong independent association with (low) Agreeableness. The results for Neuroticism and Extraversion further clarify the temperamental basis of these higher order trait dimensions; whereas those obtained for Agreeableness and Conscientiousness illustrate the importance of examining personality-affect relations at the lower order level. PMID- 1635051 TI - Manipulation in close relationships: five personality factors in interactional context. AB - This research had three basic goals: (a) to identify manipulation tactics used in close relationships; (b) to document empirically the degree of generality and specificity of tactical deployment across relationship types (mates, friends, parents); and (c) to identify links between five major personality dimensions and the usage of manipulation tactics. Twelve manipulation tactics were identified through separate factor analyses of two instruments based on different data sources: Charm, Reason, Coercion, Silent Treatment, Debasement, and Regression (replicating Buss et al., 1987), and Responsibility Invocation, Reciprocity, Monetary Reward, Pleasure Induction, Social Comparison, and Hardball (an amalgam of threats, lies, and violence). The Big Five personality factors were assessed through three separate data sources: self-report, spouse report, and two independent interviewers. Personality factors showed coherent links with tactics, including Surgency (Coercion, Responsibility, Invocation), Desurgency (Debasement), Agreeableness (Pleasure Induction), Disagreeableness (Coercion), Conscientiousness (Reason), Emotional Instability (Regression), and Intellect Openness (Reason). Discussion focuses on the consequences of the five personality factors for social interaction in close relationships. PMID- 1635052 TI - Personality and personal projects: linking big five and PAC units of analysis. AB - This article examines the relationships between classical trait units as represented by the five-factor model (e.g., Digman, 1990) and personal action construct (PAC) units as measured by Personal Projects Analysis (Little, 1983). One hundred and forty-seven students were administered the NEO Personality Inventory (Costa & McCrae, 1985) and two components of Personal Projects methodology during their first term in university. Neuroticism and Conscientiousness were related to problematic and positive project systems, respectively, with these effects generalizing across the academic and interpersonal project domains. Extraversion and Agreeableness were also associated with positive evaluations of personal projects, particularly in the interpersonal domain. Openness was distinctively linked with project initiation and value congruency. We suggest theoretical and applied implications of using PAC methods to expand and refine the classical trait research agenda. PMID- 1635053 TI - 5-lipoxygenase: properties, pharmacology, and the quinolinyl(bridged)aryl class of inhibitors. AB - In conclusion, an effective modulator of the AA cascade for the treatment of asthma and other inflammatory diseases may require 5-LO inhibitory activity as well as LTD4 antagonism in order to limit the effects of LTB4, LTD4, and 5-HPETE. The unknown role of LTC4 with respect to bronchoconstriction and mucus production could mask the efficacy of a pure LTD4 antagonist in man, whereas the chemotactic property of LTB4 for eosinophils can contribute to lung inflammation. Indeed, it is observed that the blood of patients with bronchial asthma has increased numbers of hypodense eosinophils. In addition, the formation of lipid-derived peroxide radicals, such as 5-HPETE, are believed to be responsible for various types of cellular injuries associated with the inflammatory disease process. Because inhibition of the CO pathway is thought to explain the therapeutic effects of nonsteroidal antiinflammatory agents in rheumatic diseases, a 5-LO inhibitor with CO inhibitory activity may also be desirable profile for an antiasthma agent. The validation of the LT hypothesis of disease had to wait for the demonstration of a clinical effect by either a LTD4 receptor antagonist or a LT synthesis inhibitor (5-LO inhibitor). Only very recently has this evidence become available and it is now apparent that compounds that antagonize LTD4 receptors or inhibit LT synthesis have shown clinical efficacy in a wide range of diseases. Due to the breakthrough nature of this approach, certain of these compounds are being considered for expedited development. The absence of side effects seen in the clinical trials of selective 5-LO inhibitors is gratifying and argues that LTs are not important in homeostasis. Only time will tell whether 5-LO inhibitors will take their place in the therapeutic armamentarium; however, the recent demonstration of clinical efficacy by a number of these compounds is a significant step in this direction. PMID- 1635054 TI - A series of potent HIV-1 protease inhibitors containing a hydroxyethyl secondary amine transition state isostere: synthesis, enzyme inhibition, and antiviral activity. AB - A series of HIV-1 protease inhibitors containing a novel hydroxyethyl secondary amine transition state isostere has been synthesized. The compounds exhibit a strong preference for the (R) stereochemistry at the transition state hydroxyl group. Molecular modeling studies with the prototype compound 11 have provided important insights into the structural requirements for good inhibitor-active site binding interaction. N-Terminal extension of 11 into the P2-P3 region led to the discovery of 19, the most potent enzyme inhibitor in the series (IC50 = 5.4 nM). 19 was shown to have potent antiviral activity in cultured MT-4 human T lymphoid cells. Comparison of analogs of 19 with analogs of 1 (Ro31-8959) demonstrates that considerably different structure-activity relationships exist between these two subclasses of hydroxyethylamine HIV-protease inhibitors. PMID- 1635055 TI - Synthesis and X-ray crystallographic analysis of quinazolinone cholecystokinin/gastrin receptor ligands. AB - Compounds exemplified by 2-[2-(5-bromo-1H-indol-3-yl)ethyl]-3-[3-(1- methylethoxy)phenyl]-4(3H)-quinazolinone (3, IC50 = 0.0093 microM using mouse brain membranes) represent a structurally novel series of non-peptide cholecystokinin B receptor ligands. Since asperlicin, a selective CCK-A receptor antagonist, may be regarded as a conformationally constrained 2-substituted-3 phenyl-4(3H)-quinazolinone, the progenitor of compound 3 (compound 2, 2-[2-(1H indol-3-yl)ethyl]-3-phenyl-4(3H)- quinazolinone) might therefore represent a conformationally flexible pharmacophore of the natural product. To probe possible conformational preferences for this class of receptor ligands, in particular the spatial relationship between the indole and quinazolinone rings, we prepared a series of analogues with methyl substituents on the ethylene bridge as well as congeners with different linkers. The X-ray crystal structure conformation for compound 22 (2-[2-(1H-indol-3-yl)ethyl]-3-]-3-(1-methylethoxy) phenyl]-4(3H) quinazolinone, IC50 = 0.026 microM) is extended with the two heteroaromatic rings adopting an antiperiplanar arrangement around the central sigma bond of the ethane linker, whereas the solid-state conformation for a less active analogue 19 (2-[2-(1H-indol-3-yl)-1-methylethyl]-3-[3-(1- methylethoxy)phenyl]-4(3H) quinazolinone, IC50 = 9.1 microM) is folded with the two heteroaromatic systems adopting a synclinal orientation. However, MM2 force field calculations (MacroModel, v 3.0) suggest that the energy difference between the folded and extended conformation is small. Thus, other factors such as unfavorable steric interactions may account for the difference in receptor affinity. For derivatives with one to three methylene units separating the indole and quinazolinone rings, maximal receptor binding activity was found when the distance separating the two heteroaromatic systems is defined by an ethyl group. Introducing unsaturation into the ethylene bridge of compound 3 limited the conformational flexibility of the molecule and decreased its receptor affinity greater than 2 orders of magnitude. PMID- 1635056 TI - Comparative molecular field analysis of anticoccidial triazines. AB - Comparative molecular field analysis (CoMFA) of 2-(substituted phenyl)-1,2,4 triazine-3,5(2H,4H)-diones (triazines henceforth) resulted in an excellent correlation of their anticoccidial potencies with their physical properties. Two items about this work are notable: (i) the biological data are from a whole animal infectious disease model; and (ii) for the best results CoMFA required columns of measured "lipophilicity" and "acidity" data in addition to the calculated data in the steric field and electrostatic field columns. CoMFA resulted in a quantitative description of the major steric and electrostatic field effects, and gave significant new insights to factors governing potency. The model was used to "predict" the potencies of diverse triazines not used in making the model itself. PMID- 1635057 TI - Structure-activity relationships of a series of 2-amino-4-thiazole-containing renin inhibitors. AB - A series of renin inhibitors was synthesized that contained a 2-amino-4-thiazolyl moiety at the P2 position. These derivatives are potent inhibitors of monkey renin in vitro and are selective in that they only weakly inhibit the closely related aspartic proteinase, bovine cathepsin D. Four compounds exhibited oral blood pressure lowering activity in high-renin normotensive monkeys. One of these compounds, 22 (PD 134672), was selected for further evaluation in renal hypertensive monkeys, on the basis of its superior efficacy and duration of action in the in vitro assays and the normotensive primate model. PMID- 1635058 TI - Rationally designed "dipeptoid" analogues of CCK. Acid mimics of the potent and selective non-peptide CCK-B receptor antagonist CI-988. AB - This paper outlines the synthesis of selected acid mimics of the non-peptide CCK B selective antagonist CI-988, 1. CCK-B and CCK-A binding affinities of these analogues are described and their CCK-B affinity and selectivity rationalized by consideration of the pK(a) values, charge distribution, and geometry of the respective acid mimics. Several of the compounds have CCK-B binding affinities similar to the parent carboxylic acid 1 (CCK-B, IC50 = 1.7 nM; pK(a) = 5.6) and span a pK(a) range of less than 1 (sulfonic acid 27) to greater than 9.5 (5-thio 1,2,4-triazole 24). Among the more active compounds synthesized are tricyclo[3.3.1.1(3,7)]dec-2-yl [R-(R*,R*)]-[2-[[2-[[(3-hydroxy-5 isoxazolyl)acetyl]-amino]-2- phenylethyl]amino]-1-(1H-indol-3-ylmethyl)-1-methyl 2-oxoethyl+ ++]carbamate (15), tricyclo[3.3.1.1(3,7)]dec-2-yl [R-(R*,R*)]-[1-(1H indol-3-ylmethyl)-1-methyl-2-oxo-2-[[2-[(1-oxo- 3-sulfopropyl)amino]-2 phenylethyl]amino]-ethyl]carbamate, monosodium salt (27), and tricyclo[3.3.1.1(3,7)]dec-2-yl [R-(R*,R*)]-[1-(1H-indol-3-ylmethyl)-1- methyl-2 oxo-2-[[2-[[(1H-1,2,4-triazol-5-ylsulfinyl)acetyl]a mino]-2 phenylethyl]amino]ethyl]carbamic acid (34) which have CCK-B binding affinities of IC50 = 2.6, 1.3, and 1.7 nM, CCK-A/-B ratios of 650, 780, and 550 and pK(a) values of 6.5, less than 1, and 7.0, respectively. PMID- 1635059 TI - Benzazepinone calcium channel blockers. 5. Effects on antihypertensive activity associated with N1 and aromatic substituents. AB - We have shown that the pyrrolidinylmethyl substituent on the lactam nitrogen (N1) of benzazepinone and benzothiazepinone calcium channel blocking agents is resistant to metabolic deamination and generally increases the duration and potency of antihypertensive activity in spontaneously hypertensive rats (SHR) relative to (N,N-dimethylamino)ethyl analogs. Additionally, compounds possessing a substituent on the fused aromatic ring are more resistant to metabolic deacylation of the C3 hydroxy function, which may explain why aromatic substituents also frequently increase the potency and/or duration of antihypertensive activity. Our data also indicate the increased antihypertensive activity associated with these structural modifications is independent of any effects of potency in vitro. Overall, we interpret these results to indicate that these structural modifications improve antihypertensive activity as a result of increased metabolic stability and, consequently, oral bioavailability. PMID- 1635060 TI - Studies on antidiabetic agents. 11. Novel thiazolidinedione derivatives as potent hypoglycemic and hypolipidemic agents. AB - In the course of further chemical modification of the novel antidiabetic pioglitazone (AD-4833, U-72,107), a series of 5-[4-(2- or 4-azolylalkoxy)benzyl- or -benzylidene]-2,4-thiazolidinediones was prepared and evaluated for hypoglycemic and hypolipidemic activities in insulin-resistant, genetically obese, and diabetic KKA(y) mice. Replacement of the 2-pyridyl moiety of pioglitazone by a 2- or 4-oxazolyl or a 2- or 4-thiazolyl moiety greatly enhanced in vivo potency. The corresponding 5-benzylidene-type compounds, in which a methine was used as a linker between the benzene ring and the thiazolidinedione ring, also had potent biological activity. Among the compounds synthesized, 5-[4 [2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzyl]-2,4- thiazolidinedione (18) exhibited the most potent activity, more than 100 times that of pioglitazone. The synthesis and structure-activity relationships for this novel series of derivatives are detailed. PMID- 1635061 TI - N-[4-[[(3,4-dihydro-4-oxo-1,2,3-benzotriazin-6- yl)methyl]amino]benzoyl]-L glutamic acid, a novel A-ring analogue of 2-desamino-5,8-dideazafolic acid. AB - N-[4-[[(3,4-Dihydro-4-oxo-1,2,3-benzotriazin-6- yl)methyl]amino]benzoyl]-L glutamic acid ("2-aza-2-desamino-5,8- dideazafolic acid", ADDF) was synthesized from 2-amino-5-methylbenzamide via a four-step sequence consisting of diazotization, benzylic bromination, condensation with dimethyl N-(4 aminobenzoyl)-L-glutamate, and ester hydrolysis. ADDF was an inhibitor of recombinant mouse thymidylate synthase; inhibition was competitive with 5,10 methylenetetrahydrofolate as variable substrate (Ki = 2.3 microM). It was a substrate for murine folylpolyglutamate synthetase with kinetic characteristics (Km = 28 microM) comparable to those of aminopterin, and it inhibited the growth of L1210 cells in culture (IC50 = 0.52 microM). The structural modification of the A-ring embodied in ADDF appears to offer a novel, heretofore unexplored approach to the design of TS inhibitors. PMID- 1635062 TI - Synthesis and structure-activity relationships of cephalosporins with C-3' catechol-containing residues. AB - Cephalosporins with new catechol substituents at C-3' have been synthesized, including novel compounds with C-3' carbon-carbon bonds. Many of these compounds have high potency against Gram-negative bacteria, in particular against resistant strains like Pseudomonas aeruginosa. Structure-activity relationships are discussed in terms of their dependence on the pKa of the C-3' catechol and also in terms of steric and conformational factors of the C-3' substituent. The best overall properties were found in compounds with a bulky and/or conformationally restricted acidic C-3' catechol. PMID- 1635063 TI - Pharmacokinetics of catechol cephalosporins. The effect of incorporating substituents into the catechol moiety on pharmacokinetics in a marmoset model. AB - Two series of cephalosporins A and B have been synthesized, bearing at C-3' catechols substituted with various electron withdrawing groups (Y) and differing links (X), and were evaluated for their in vitro antibacterial activity and their pharmacokinetics in marmosets. Compounds in series A, bearing an isobutyric oxime substituent, proved to be highly active against Gram-negative organisms and were especially noteworthy for showing long elimination phase (beta) half-lives in marmosets. It was established that introduction of electron withdrawing substituents greatly increased the beta half-lives of compounds (5, X = NHCO, Y = H, t1/2 = 1.25 h, AUC = 27 mg/h per L; 11, X = NHCO, Y = 5-Cl, t1/2 = 4.5 h, AUC = 638 mg/h per L) and that the nature of the link also influenced t1/2, the highest values being obtained when X = NHCO and OCO. Acidities (pKa values) of the substituted catechols were measured, and relationships between the acidities and half-lives were evaluated. Thus it was established that the more acidic catechols gave the longest half-lives (12, X = NHCO, Y = 2,5-Cl2, t1/2 = 8.2 h, AUC = 461 mg/h per L). Further elaboration of the catechol to bicyclic systems maintained good pharmacokinetics when the pKa was sufficiently acidic. PMID- 1635064 TI - Nonpeptide angiotensin II receptor antagonists: synthetic and computational chemistry of N-[[4-[2-(2H-tetrazol-5-yl)-1-cycloalken-1- yl]phenyl]methyl]imidazole derivatives and their in vitro activity. AB - A series of nonpeptide angiotensin II receptor antagonists was synthesized and tested in vitro to investigate requirements for recognition by and binding to AT1 receptors. Compared to a known series of N-(biphenylylmethyl)imidazoles, including losartan (DuP 753), which has a more rigid conformation in the 2' tetrazolylbiphenyl moiety, the new series replaces the terminal phenyl with cycloalkenyls. Compounds were made with five- to seven-membered rings and with either a hydroxymethyl (3) or carboxyl (4) group at the 5 position on the imidazole ring. The effects of the lipophilicity and steric bulk of the terminal ring system, the amount of pi-electron density in the terminal ring, and the relative spatial proximity of the tetrazolyl and the middle phenyl are explored in terms of binding affinity to AT1 receptors in rat adrenal glomerulosa and rabbit aorta. The physicochemical variables of the new compounds were quantitated by computational chemistry and compared to those of losartan and its carboxyl metabolite. Potency at the AT1 receptors is maximized when the terminal ring is six-membered; an aromatic ring binds better than a cycloalkenyl ring. The 5 carboxyimidazole compounds show higher affinity than the 5-hydroxymethyl series. PMID- 1635065 TI - Metabolism of 5-hydroxytryptamine by brain synaptosomes and microsomes in the presence of cysteine and glutathione. AB - Incubation of 5-hydroxytryptamine (1) with L-cysteine and pig or bovine brain microsomes and an NADPH-generating system or with synaptosomes results in the rapid formation of the (2R,4R)- and (2S,4R)-epimers of 2-[(5-hydroxy-1H-indol-3 yl)methyl]thiazolidine. Incubation of 1 and glutathione under the same experimental conditions yields the (2R,4R)- and (2S,4R)-epimers of alpha-amino-4 [[(carboxymethyl)amino]carbonyl]-2-[(5-hydroxy-1H- indol-3-yl)methyl]-delta-oxo-3 thiazolidinepentanoic acid. These various thiazolidine derivatives are formed by nucleophilic addition of the thiol residues of cysteine or glutathione to the aldehyde group of 5-hydroxyindole-3-acetaldehyde (2), the primary product of the monoamine oxidase-mediated oxidative deamination of 1. The facile reaction of cysteine and glutathione with 2 might represent a mechanism designed to scavenge the biogenic aldehyde and therefore to prevent its alkylation of key intraneuronal protein nucleophiles. PMID- 1635066 TI - Acetazolamide-like carbonic anhydrase inhibitors with topical ocular hypotensive activity. AB - New carbonic anhydrase (EC 4.2.1.1) inhibitors were synthesized as potential drugs for the topical treatment of glaucoma. They were obtained by substituting the acetyl group of acetazolamide and methazolamide with bicarboxylic acids of different chain length (C4-C6). The terminal carboxyl was either kept free or esterified with alcohols of different size (C1-C12). A gamma-aminovaleric derivative was also prepared. All compounds proved active as carbonic anhydrase inhibitors in vitro, with an average IC50 of about 0.5 microM. Some proved also to be topically active in vivo in lowering the artificially elevated intraocular pressure in rabbits. The most active compound, carrying a succinic acid side chain, is the most soluble in aqueous buffers. Its duration of action is about 8 h and it is under evaluation as a topical antiglaucoma drug. It is hypothesized that the duration of action could be longer in compounds having both the same high water solubility and partition coefficient. PMID- 1635068 TI - 1-(5'-Fluoro-6'-hydroxy-5',6'-dihydrouracil-5'-yl)-5-fluorouracil, a novel N(1) C(5)-linked dimer that releases 5-fluorouracil by radiation activation under hypoxic conditions. PMID- 1635067 TI - Synthesis of the acridone alkaloids glyfoline and congeners. Structure-activity relationship studies of cytotoxic acridones. AB - Glyfoline (4, 1,6-dihydroxy-10-methyl-2,3,4,5-tetramethoxyacridin-9-one) and its congeners were synthesized for evaluation of their cytotoxicity. A detailed structure-activity relationships (SAR) of these acridone derivatives were also studied. To study the SAR of glyfoline analogues, substituent(s) at C-1 and C-6 and at the heterocyclic nitrogen of glyfoline nucleus were modified. Nitro- and amino-substituted glyfoline analogues were also synthesized to study the effects of substituent(s) (electron-withdrawing vs electron-donating) on their cytotoxicity. These compounds were synthesized via the Ullmann condensation of anthranilic acids with iodobenzenes or 2-chlorobenzoic acids with aniline derivatives. The SAR studies showed that 1-hydroxy-9-acridones were more active than their 1-OMe derivatives against cell growth of human leukemic HL-60 cells in culture. Replacement of NMe of glyfoline with NH or N(CH2)2NEt2 resulted in either total loss or dramatic reduction of cytotoxicity. Glyfoline congeners with nitro function at the A-ring were inactive, while compounds with amino substituent were shown to be cytotoxic in vitro. PMID- 1635069 TI - Praesomal nerves in Leptorhynchoides thecatus (Acanthocephala: Rhadinorhynchidae). AB - Investigated by light microscopy, the nerve pathways are described for the first time in the praesoma of a species of Rhadinorhynchidae. The pathways are described for 18 nerves, eight paired and two single, which originate from the cerebral ganglion and a post-ganglionic cell and terminate in the body wall musculature and the proboscis. The location of three commissures formed by these nerves is also described. PMID- 1635070 TI - Internal reproductive system in adult males of the genus Camponotus (Hymenoptera: Formicidae: Formicinae). AB - Descriptions are provided of the histology and ultrastructure of the male internal reproductive tracts from three species of Camponotus, representing three subgenera. This study is the first to provide ultrastructural information on the testes (including spermatogenesis and spermiogenesis), seminal vesicles, and accessory glands in ants. Testes contain about ten follicles each, and each follicle is capable of producing hundreds of cysts in which spermatozoa develop. Structural evidence of meiosis in late pupal testes includes cytoplasmic bridges between spermatocytes, centriole elimination, and fusion of mitochondria. Developing spermatids are in close contact with cyst cells in the region of the acrosome. Mature spermatozoa are similar in ultrastructure to those described previously for two other subfamilies of ants (Myrmicinae and Dolichoderinae). The ultrastructure of the seminal vesicle suggests that it is not merely a passive organ for sperm storage. Large numbers of both mitochondria and membranous whorls suggest a pH-regulating and/or hormonal function. The accessory gland is made up of secretory cells that contain a diversity of secretory granules. SDS-PAGE reveals several proteins found in the accessory glands but absent in the adjacent genitalia. Preliminary analyses indicate that carbohydrate is an important component of accessory gland secretions. PMID- 1635071 TI - Effects of hypothermia and rewarming on phospholipase C-evoked glycerol output in rat myocardial cells. AB - The combined action of phosphatidylcholine preferring phospholipase C (PC-PLC) and intracellular lipases has recently been shown to cause glycerol output in energy deprived rat cardiomyocytes. In the present study we examined the effect of hypothermia and rewarming on PC-PLC evoked glycerol output in freshly isolated, calcium-tolerant myocytes. The cells were preincubated for 60 min at hypothermic (5 degrees C) or normothermic (37 degrees C) conditions in Krebs Henseleit bicarbonate buffer (pH 7.4) supplemented with 1 mM DL-carnitine, 1% B.S.A. and 5 mM glucose. Addition of PC-PLC resulted in a significantly higher (P less than 0.05) output of glycerol in myocytes undergoing rewarming than in myocytes kept constantly at 5 degrees C or 37 degrees C. The values obtained for PC-PLC induced glycerol output (difference in glycerol output between incubations with and without PC-PLC) were 6.77 +/- 2.6 (37 degrees C), 4.54 +/- 1.7 (5 degrees C) and 22.85 +/- 5.9 (5-37 degrees C) nmol/10(6) cells.h. Rewarming in addition caused a significantly higher (P less than 0.05) leakage of lactate dehydrogenase (LDH) from the rewarmed cells as compared to cells at constant temperatures (5 degrees C or 37 degrees C). However, there was no additional effect of PC-PLC on LDH leakage. The elevated PC-PLC induced glycerol output in rewarmed myocytes was not related to a fall in the percentage of rod-shaped cells or a reduced cellular content of ATP, since no differences could be detected between the various myocyte preparations with respect to these parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635072 TI - Reduced adenylyl cyclase inhibition by carbachol and GTP during acute myocardial ischaemia. AB - Acute myocardial ischaemia frequently is complicated by ventricular tachyarrhythmias. These arrhythmias are in part due to an increased susceptibility of myocardial cells to adenylyl cyclase stimulation by catecholamines [1]. As adenylyl cyclase underlies an endogenous dual regulation by stimulatory and inhibitory receptor systems, adenylyl cyclase stimulation can be counteracted by the activation of receptors like the muscarinic M2 receptor [2]. Therefore, the effect of myocardial ischaemia on muscarinic receptor and "inhibitory" guanine nucleotide binding proteins (G(i)) mediated inhibition of adenylyl cyclase was studied. During 5 min of myocardial ischaemia, carbachol mediated inhibition of forskolin and isoproterenol stimulated adenylyl cyclase was reduced by 30% and 50%, respectively. Hormone independent inhibition of adenylyl cyclase by the nonhydrolyzable GTP-analogue guanosine 5'-[beta gamma imido]triphosphate (Gpp(NH)p) was reduced by 46%. In contrast, the amount of G(i), as determined by pertussis toxin catalyzed ADP-ribosylation, remained constant during 15 min of ischaemia. The impaired function of muscarinic receptor linked signal transduction during early myocardial ischaemia could contribute to the occurrence of ischaemia induced tachyarrhythmias by a reduced ability to counteract adenylyl cyclase activation. PMID- 1635073 TI - Neutrophils contribute to TNF induced myocardial tolerance to ischaemia. AB - Sublethal endotoxin (ETX) pretreatment of rats induces protection from cardiac ischaemia-reperfusion injury. This protective state is associated with increased endogenous myocardial catalase activity. Since tumour necrosis factor (TNF) is one mediator of ETX effects, we hypothesized that (TNF) pretreatment of the rat (30 micrograms/kg ip) 36 h prior to cardiac ischaemia-reperfusion could induce myocardial protection. We found that TNF administration increased both myocardial tolerance to ischaemia reperfusion injury (modified Langendorff, buffer perfusion, global, normothermic ischaemia) and myocardial catalase activity at 36 h. Moreover, we found that 6 h after TNF administration, myocardial hydrogen peroxide (H2O2, assessed by aminotriazole-H2O2 inactivation of catalase) and myocardial neutrophil accumulation (assessed by histology) were both increased. When neutrophil function was inhibited either by neutrophil depletion (vinblastine) or by ibuprofen treatments of the rat before TNF, the protection previously apparent at 36 h was blocked. We conclude that TNF can induce myocardial resistance to ischaemia reperfusion injury. This protection is related to prior tissue neutrophil accumulation and concomitant increases in H2O2 levels. PMID- 1635074 TI - Effect of amiodarone therapy on the time course of myocardial phospholipid hydrolysis during in vitro total ischaemia in cat hearts. AB - The effects of chronic amiodarone therapy on myocardial phospholipid hydrolysis induced by total in vitro ischaemia were investigated in cat hearts. Chronic treatment of cats with amiodarone (30 mg/kg/day, orally) for 6 weeks resulted in a sufficient uptake of the drug reaching tissue levels of 83 +/- 13 & 122 +/- 22 microM (n = 12) for amiodarone and its principle metabolite, desethylamiodarone, respectively. This was accompanied by a significant increase (37%, P less than 0.001) in total phospholipid content of heart in treated as compared to untreated animals. Upon in vitro total ischaemia, these endogenous drug levels were sufficient to attenuate significantly hydrolysis of membrane phospholipid. The degree of attenuation was dependent upon the duration of ischaemic insult. In this regard, protection against phospholipid losses by amiodarone treatment was significantly more in the later irreversible phase of ischaemic injury whether studied in an in vitro total ischaemia model or in an isolated perfused heart preparation. Similar trend was observed in the relative accumulation of lysophospholipid and non-esterified fatty acid levels during ischaemia, i.e. both were significantly attenuated by amiodarone treatment. However, in contrast to the fatty acid data, the net changes in lysophospholipids per gram tissue wet weight were similar in treated and untreated animals, suggesting that the protective effects of amiodarone may have involved other enzymes including phospholipase C and D. Also, during the entire time course studied, all the phospholipid classes appeared to be affected to more or less a similar degree, indicating that the effects of the drug may have manifested in other subcellular compartments besides lysosomes. However, at all time periods studied, the net release of eicosatetraenoic and docosahexaenoic acid (fatty acids occupying primarily sn-2 position of phospholipids) was different, release of the former fatty acid being inhibited more than the latter, suggesting specific interaction of amiodarone with the molecular species of phospholipid. The data suggest that amiodarone attenuates ischaemia-induced membrane lipid abnormalities in part through modulation of phospholipid metabolism, and that this effect may be one of the key determinants which contribute to its antiarrhythmic properties during acute ischaemia. PMID- 1635075 TI - Mechanism of the membrane depolarization induced by oxidative stress in guinea pig ventricular cells. AB - Mechanism of the membrane depolarization induced by oxidative stress was examined using ion-selective microelectrode and patch clamp techniques. In guinea-pig papillary muscles stimulated at 0.5 Hz, cumene hydroperoxide (CH) at a concentration of 300 microM decreased the resting membrane potential and shortened the action potential, concomitantly with muscle contracture. The membrane depolarization was not associated with a significant decrease in intracellular potassium ion activity, indicating that the depolarization is not due to a decrease in potassium equilibrium potential resulting from leak of intracellular K+. In isolated guinea-pig ventricular cells. CH (10-30 microM) consistently decreased the inward rectifier potassium current and slightly decreased the calcium current. In cell-attached patches CH inhibited the opening of the inward rectifier K+ channel without affecting the unit amplitude of the single channel current. Thus, the depolarization of the resting membrane induced by oxidative stress is, at least in part, due to the inhibition of the inward rectifier K+ channel activity, and may play an important role in the genesis of reperfusion-induced arrhythmias. PMID- 1635076 TI - Reductive activation of mitomycin C: a delicate balance. PMID- 1635077 TI - Ken Olden has clear vision as NIEHS director. PMID- 1635078 TI - Second round of NCI funds goes to other institutes. PMID- 1635079 TI - Drug firms, countries hope to cash in on natural products. PMID- 1635080 TI - Biodiversity treaty still unsigned by U.S. PMID- 1635081 TI - Top July stories are "5 a day," new cancer risks. PMID- 1635082 TI - ACS focusing on breast cancer detection. PMID- 1635083 TI - Cancer pain in the elderly needs special attention. PMID- 1635084 TI - Recommendations on predictive testing for germ line p53 mutations among cancer prone individuals. PMID- 1635085 TI - Relationship between mammographic and histological risk factors for breast cancer. AB - BACKGROUND: Information on breast cancer risk can be obtained both from the histological appearance of the breast epithelium in biopsy specimens and from the pattern of parenchymal densities in the breast revealed by mammography. It is not understood, however, how parenchymal densities influence breast cancer risk or whether these densities are associated with histological risk factors. PURPOSE: We have estimated, in a large cohort of women, the relative risk of detecting carcinoma in situ, atypical hyperplasia, hyperplasia without atypia, or nonproliferative disease in biopsy specimens from women with different extents of mammographic density. We also examined the association between these histological classifications and radiological features present specifically at the biopsy site. METHODS: The source of study material was a population of women aged 40-49 years who were enrolled in the Canadian National Breast Screening Study (NBSS). Mammograms from women who had undergone a biopsy (n = 441) and from a comparison group of women (n = 501) randomly selected from the mammography arm of the NBSS were classified according to the extent of mammographic density. The corresponding histological slides were independently classified by a review pathologist. RESULTS: Compared with women showing no mammographic densities, women with the most extensive densities (i.e., occupying greater than 75% of the breast volume) had a 9.7 times greater risk of developing carcinoma in situ or atypical hyperplasia (95% confidence interval [CI] = 1.75-53.97), a 12.2 times greater risk of developing hyperplasia without atypia (95% CI = 2.97-50.14), and a 3.1 times greater risk of developing non-proliferative disease (95% CI = 1.20 8.11). The gradients in risk were not monotonic across the five classifications of mammographic density. The association could not be explained by the presence of mammographic densities at the biopsy site, but calcification at the biopsy site was strongly associated with high-risk histological changes (relative risk = 24; 95% CI = 5.0-156.0). CONCLUSIONS: These results suggest that the radiological patterns referred to as mammographic dysplasia may influence breast cancer risk by virtue of their association with high-risk histological changes in the breast epithelium. IMPLICATIONS: Identification of the factors responsible for high-risk histological changes may offer new insights into the etiology of breast cancer and potentially lead to the development of methods for its prevention. PMID- 1635086 TI - Bioactivation of mitomycin C by xanthine dehydrogenase from EMT6 mouse mammary carcinoma tumors. AB - BACKGROUND: Mitomycin C is an antineoplastic antibiotic requiring bioactivation to an alkylating species or to an intermediate capable of generating oxygen radicals for its toxic effect. The enzymes responsible for the in vivo activation of mitomycin C have been proposed to include NADPH-cytochrome-c reductase, DT diaphorase, and xanthine oxidase. PURPOSE: In this study, xanthine dehydrogenase, an enzyme structurally similar to xanthine oxidase, was assessed for its ability to activate mitomycin C. Partially purified xanthine dehydrogenase, from EMT6 mouse mammary tumors, was investigated for its ability to bioactivate mitomycin C under both aerobic and hypoxic conditions. METHODS: We conducted this analysis by measuring mitomycin C-induced oxygen consumption, alkylating potential, and mitomycin C consumption and metabolite formation as determined by high-pressure liquid chromatography analysis. RESULTS: Bioactivation of mitomycin C by xanthine dehydrogenase under both aerobic and hypoxic conditions gave rise to the formation of a metabolite, 2,7-diaminomitosene. Formation of this metabolite and alkylating ability were greater under hypoxic than under aerobic conditions and were increased when the pH was decreased from 7.4 to 6.0. Mitomycin C consumption was the same under both aerobic and hypoxic conditions and was independent of pH. Oxygen consumption studies showed that xanthine dehydrogenase-activated mitomycin C consumed oxygen at a much lower rate than xanthine oxidase-activated mitomycin C. CONCLUSIONS: Xanthine dehydrogenase-activated mitomycin C appears to be a good alkylating species but a relatively poor generator of reactive oxygen when compared with xanthine oxidase activation under aerobic conditions. IMPLICATION: Xanthine dehydrogenase may play an important role in the bioactivation of mitomycin C to an alkylating species under both aerobic and hypoxic conditions. PMID- 1635087 TI - l-folinic acid versus d,l-folinic acid in rescue of high-dose methotrexate therapy in children. AB - BACKGROUND: At this time, folinic acid (FA) is commercially available as the racemic mixture d,l-FA, whose biological activity is supported by natural l-FA. The administration of d,l-FA results in the accumulation of d-FA in plasma relative to the active l-FA form; in vitro studies have shown that d-FA can compete with the polyglutamation of methotrexate (MTX). PURPOSE: Our purpose was to compare, on a pharmacokinetic, biological, and clinical basis, the racemic mixture d,l-FA with the pure l-FA in rescue of high-dose MTX therapy (5 g/m2) in children with acute lymphocytic leukemia (ALL). METHODS: Eighteen children with ALL were entered in this trial, which was planned with a crossover design. Four cycles of MTX were administered to each patient, and rescue was achieved orally every 6 hours at a dose of 12 mg/m2 for d,l-FA and 6 mg/m2 for pure l-FA. The d,l FA and l-FA rescues were alternated from one cycle to the next. d-FA, l-FA, and the active metabolite 5-methyltetrahydrofolate (5-MTHF) were measured in plasma using a stereospecific high-performance liquid chromatography assay. RESULTS: Considering total active folate levels (l-FA + 5-MTHF), mean residual concentrations were similar for rescue by d,l-FA and l-FA, after two and six intakes, respectively: 92 and 186 nM for d,l-FA rescue versus 100 and 184 nM for l-FA rescue. Intra-individual comparison of total active folates (l-FA + 5-MTHF) did not show any significant difference between d,l-FA rescue and l-FA rescue. After administration of d,l-FA, the accumulation of d-FA in plasma was confirmed. For both types of FA rescue, MTX terminal half-lives were identical (average value, 13.9 hours). Considering each type of toxic effect (hematologic, hepatic, renal, and digestive), there was no significant difference in the proportion of toxic cycles following l-FA rescue or d,l-FA rescue. CONCLUSION: The administration of the pure l-FA, compared with the administration of the racemic mixture, results in comparable blood profiles of active folates and MTX, leads to equivalent treatment tolerance, and avoids the plasma accumulation of d-FA. PMID- 1635088 TI - Hematopoietic growth-promoting effects of natural killer cells in mice in response to in vivo administration of human interleukin-2. AB - BACKGROUND: Interleukin-2 (IL-2) is currently being evaluated as an anti neoplastic agent because of its stimulatory effects on the immune system. However, little is known about the effects of systemic IL-2 administration on hematopoietic parameters. PURPOSE: Recombinant human IL-2 (rHuIL-2) was administered to mice to evaluate its in vivo hematopoietic effects. The mechanism underlying the effects of rHuIL-2 administration was also determined. METHODS: Mice were given 5 x 10(4) IU of rHuIL-2 for 5 days, and their hematopoietic progenitor cell status was determined as measured by growth in soft agar. Antiserum to natural killer (NK) cell-specific markers was used to ascertain if NK cells were responsible for the hematopoietic effects of rHuIL-2. NK cells were purified and cultured in vitro with rHuIL-2 and then adoptively transferred into syngeneic mice to determine the effects on hematopoiesis. RESULTS: Treatment of mice with rHuIL-2 resulted in a significant increase in bone marrow and splenic hematopoietic progenitor cell content. Mice with severe combined immune deficiency (SCID), which lack T cells and B cells yet have NK cells, also responded to the myelostimulatory effects of rHuIL-2. However, removal of NK cells from the SCID mice with antiserum to NK cell-specific markers abrogated the myelostimulatory properties of rHuIL-2. Adoptive transfer of NK cells that were propagated in vitro with rHuIL-2 into mice also resulted in an increase in splenic hematopoietic progenitor cells. CONCLUSIONS: rHuIL-2 exerts significant myelostimulatory effects after in vivo administration, and NK cells are responsible for at least some of these effects. IMPLICATIONS: These results suggest that NK cells and rHuIL-2 may be of use clinically to promote hematopoiesis after bone marrow transplantation or in the face of other myelotoxic therapy in the treatment of cancer. PMID- 1635089 TI - Intrathecal dacarbazine treatment of leptomeningeal malignant melanoma. PMID- 1635090 TI - Diuretic use and risk factors for cancer: results of animal studies. PMID- 1635091 TI - Indole-3-carbinol. PMID- 1635092 TI - Men, women, and murder: gender-specific differences in rates of fatal violence and victimization. AB - To study the potential differences that distinguish homicides involving women as victims or offenders from those involving men, we analyzed Federal Bureau of Investigation Uniform Crime Reports data on homicides that occurred in the United States between 1976 and 1987. Only cases that involved victims aged 15 years or older were included. Persons killed during law enforcement activity and cases in which the victim's gender was not recorded were excluded. A total of 215,273 homicides were studied, 77% of which involved male victims and 23% female victims. Although the overall risk of homicide for women was substantially lower than that of men (rate ratio [RR] = 0.27), their risk of being killed by a spouse or intimate acquaintance was higher (RR = 1.23). In contrast to men, the killing of a woman by a stranger was rare (RR = 0.18). More than twice as many women were shot and killed by their husband or intimate acquaintance than were murdered by strangers using guns, knives, or any other means. Although women comprise more than half the U.S. population, they committed only 14.7% of the homicides noted during the study interval. In contrast to men, who killed nonintimate acquaintances, strangers, or victims of undetermined relationship in 80% of cases, women killed their spouse, an intimate acquaintance, or a family member in 60% of cases. When men killed with a gun, they most commonly shot a stranger or a non-family acquaintance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635093 TI - Laparoscopy in the evaluation of the intrathoracic abdomen after penetrating injury. AB - Penetrating trauma to the intrathoracic abdomen is a difficult clinical problem, especially with reference to the detection of diaphragmatic injuries. A retrospective analysis of 657 laparotomies for penetrating abdominal trauma at our institution revealed 78 laparotomies with negative results. The majority (44.8%) were for wounds in the lower chest and upper abdomen. The role of laparoscopy in evaluating these difficult areas was studied in 40 (34 stab wounds and 6 gunshot injuries) patients. Fifteen stab wounds and five gunshot wounds were nonpenetrating. Laparoscopy revealed eight clinically unsuspected diaphragmatic lacerations in seven patients. Twenty patients had hemoperitoneum. Five patients with omental bleeding and abdominal wall bleeding and four with nonbleeding liver lacerations underwent nontherapeutic laparotomies. One patient with a nonbleeding liver laceration was observed successfully without laparotomy. Ten of the 20 patients with hemoperitoneum had therapeutic laparotomies. The incidence of diaphragmatic lesions discovered by laparoscopy in this series was comparable with that reported after a mandatory laparotomy for thoracoabdominal wounds. It is concluded that laparoscopy is an excellent modality for the evaluation of the intrathoracic abdomen and the diaphragm. PMID- 1635094 TI - Mild head injury: a plea for routine early CT scanning. AB - We reviewed the records of 1538 mild head injury patients admitted during a 4 1/2 year period to the Southern New Jersey Regional Trauma Center. All patients had experienced brief loss of consciousness or amnesia, but had a normal or near normal neurologic examination on admission, with Glasgow Coma Scale (GCS) scores of 13-15 and no focal neurologic deficit. Routine urgent cranial CT scans were obtained on all patients, and correlations between skull fractures and intracranial lesions investigated. Two hundred sixty-five patients (17.2%) harbored 340 lesions on CT scans, of which 131 were fractures and 209 were intracranial abnormalities. Fifty-eight patients needed surgery for their intracranial lesions; 23 of them had no skull fractures. None of the 1339 patients without CT evidence of intracranial lesions deteriorated under observation. We conclude that clinical observation with or without skull x-ray films is inadequate to rule out potentially dangerous intracranial lesions in apparently mild head injuries. If there is a history of loss of consciousness or amnesia, an immediate CT scan is indicated. If the results of the CT scan are normal and there are no other indications for admission, these patients may be safely discharged. PMID- 1635095 TI - Antibiotic-primed fibrin gel improves outcome in contaminated splenic injury. AB - Fibrin gel (FG) has recently been shown to be bactericidal in the management of contaminated hepatic injury; antibiotic loading of fibrin gel (AFG) may augment this effect. We evaluated the antimicrobial properties of FG and AFG in a rat model of contaminated splenic injury. Fibrin gel was made from centrifuged plasma of separate donor rats and bovine thrombin. Antibiotic fibrin gel was similarly produced following intravenous injection of 70 mg/kg ticarcillin. Male Holtzman rats (250-300 g) were anesthetized and a laparotomy done. The abdomen was contaminated with 1 x 10(7) Bacteroides fragilis and the spleen transected in the midportion. Treatment consisted of splenorrhaphy (S) (n = 7), FG application (n = 7), or AFG (n = 7). The animals were autopsied at 1 week to evaluate abscess formation and abdominal adhesions (grade I = none, grade II = mild, grade III = severe). Antibiotic/fibrin gel significantly decreased abscess formation following splenic injury when compared with S (2 of 7 vs. 7 of 7; p less than 0.05 by ANOVA) without an increase in adhesions. Fibrin gel also decreased abscess formation but not significantly (4 of 7 vs. 7 of 7). Histologic analysis confirmed the beneficial effect of FG and AFG on wound healing. The bactericidal effect of FG is improved by antibiotic loading in contaminated intraabdominal injury. PMID- 1635096 TI - Packing and re-exploration for patients with nonhepatic injuries. AB - We retrospectively reviewed the clinical records of 11 patients admitted to the trauma service at Kings County Hospital who underwent packing and temporary closure for severe nonhepatic injuries. The mean ISS was 37 and the mean Abdominal Trauma Index value was 48. Operative findings included 17 major vascular injuries. Although the mean blood pressure was 105 mm Hg during the procedure, the patients required an average of 17 units of blood and all were acidotic, hypothermic, and coagulopathic. Acidosis persisted in all patients and the mean base excess was -13 at closure. A conscious decision was made to terminate the procedure when surgical bleeding was controlled. Patients were resuscitated and warmed in the ICU and returned to the operating room within 48 hours. Seven of the 11 patients survived. Of the eight patients who survived to return to the operating room, all required gastrointestinal procedures at re exploration. This preliminary experience supports packing to control coagulopathic bleeding, use of temporary abdominal closure, and further ICU resuscitation with a planned second laparotomy for definitive management of gastrointestinal injuries in patients with severe nonhepatic injuries. PMID- 1635097 TI - A pediatric trauma center without a pediatric surgeon: a four-year outcome analysis. AB - Approximately 25% of all injury victims are in the pediatric age group, and one in four injured children will require a pediatric trauma center. According to the American College of Surgeons as well as many state guidelines, a level I pediatric trauma team should be directed by a pediatric surgeon. In 1986, the pediatric surgeon left our pediatric trauma center, but the center remained open under a cooperative effort by the adult trauma surgeons and pediatric intensivists. We have retrospectively reviewed the charts of all pediatric trauma patients (age less than or equal to 15 years) for the subsequent 4 years to determine the outcome of treatment without a pediatric surgeon. During this period, we treated 303 pediatric patients with multiple or serious single-system injuries. The mean age was 6.9 +/- 0.3 (SEM) years and 66% were boys. Falls were the cause of injury in 31% of the patients, with pedestrian/bicycle, motor vehicle crashes, and penetrating injuries resulting in 26%, 19%, and 3% of the injuries, respectively. The mean ISS was 15.6 +/- 0.8, and 73% of the patients had at least one AIS greater than or equal to 3. Surgical procedures were required in 48% of the patients. There were 27 deaths in this group, most commonly related to head injury (89%). The mean Pediatric Trauma Score of the patients who died was 1.6 +/- 0.8 and no patient with a Pediatric Trauma Score greater than 7 died.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635098 TI - The reaction of copper and other projectile metals in body tissues. AB - To determine the effect of copper in tissue, copper specimens, along with other metals commonly used in firearm projectiles, were implanted into rats. Copper consistently produced a necrotic, abscesslike reaction in all tissues tested. Nickel produced a similar reaction, although of lesser magnitude. Aluminum, zinc, and lead produced no significant tissue reaction. PMID- 1635099 TI - A new method of diagnosing diaphragmatic injury using intraperitoneal technetium: case report. AB - The diagnosis of diaphragmatic laceration following blunt or penetrating trauma is often difficult to establish. Delay in recognition of this injury can be life threatening, resulting in herniation of abdominal viscera with possible strangulation or respiratory embarrassment. Previous animal studies from our institution have documented that intra-abdominal instillation of technetium sulfur colloid is a sensitive method to diagnose diaphragmatic disruption. We now present a case of diaphragmatic injury where the preoperative diagnosis was accurately made using this method when other imaging studies were inconclusive. PMID- 1635101 TI - Predictors of blinding or serious eye injury in blunt trauma. AB - Multivariate analysis was used to identify factors predicting injury and visual outcome in 94 blunt trauma patients evaluated for eye injuries among 6700 admissions to a level I trauma center over a 29-month period. Patients with penetrating eye injuries were excluded from this review. Eye injury was detected in 93% or 87 of the patients evaluated. Seven percent of eye injuries resulted in blindness, 22% were serious (visual acuity between 20/40 and 20/200 or eye injury requiring surgery), and 71% were temporary (final visual acuity of 20/40 or better). The presence of an afferent pupillary defect or a nonreactive pupil was the most important factor in predicting the severity of eye injury (p = 0.0023), followed by facial fractures (p = 0.0084), and no eye opening or eye opening to pain within the Glasgow Coma Scale (p = 0.02). Eye injury is an infrequent complication of blunt trauma. Appropriate consultation for evaluation of this problem can be obtained based on findings from the initial history and screening physical examination. PMID- 1635100 TI - Salmonella typhi splenic abscess in an intravenous drug abuser following splenorrhaphy: case report. AB - A recent case of posttraumatic splenic abscess in an HIV-positive intravenous drug abuser following a splenic salvage procedure is reported. With the recent trend toward splenic preservation and the ever-increasing population of HIV positive, immune-compromised patients, the complication of splenic abscess may become more common. PMID- 1635102 TI - Experimental cardiac tamponade with a myocardial wound: the effect of rapid intravenous infusion of saline. AB - In order to demonstrate that the evolution of cardiac tamponade from a ventricular wound is different from that without myocardial wounding, the effects of a rapid infusion of saline solution on hemodynamic behavior and pericardial pressure (PP) were evaluated in dogs with cardiac tamponade caused by ventricular perforation (group C), animals without cardiac tamponade (group A), and animals with cardiac tamponade induced by infusion of saline into the pericardium (group B). We found that blood pressure (BP) increased from 107.5 +/- 15.5 mm Hg to 126 +/- 4 mm Hg in group A; increased from 64.5 +/- 17.9 mm Hg to 117.5 +/- 22.17 mm Hg in group B; and increased from 60.75 +/- 46.5 mm Hg to 76 +/- 14.4 mm Hg in group C. Central venous pressure (CVP) increased from 3.75 +/- 0.96 cm H2O to 9.5 +/- 3.3 cm H2O in group A; increased from 8 +/- 2.4 cm H2O to 16.25 +/- 3.1 cm H2O in group B; and rose from 7.75 +/- 2.6 cm H2O to 20.66 +/- 5.03 cm H2O in group C. Cardiac output (CO) increased from 3.9 +/- 1.2 L/min to 18.93 +/- 3.96 L/min in group A; increased from 1.23 +/- 0.3 L/min to 5.4 +/- 1.7 L/min in group B; and increased from 1.8 +/- 0.66 L/min to 3.53 +/- 1.31 L/min in group C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635103 TI - Multivariate population-based analysis of the association of county trauma centers with per capita county trauma death rates. AB - The purpose of this study was to utilize a large population-based data base to determine the association of trauma centers with per capita county trauma death rates. METHODS: Per capita county trauma death rate, the dependent variable in the model, was obtained from a well-validated state Medical Examiner's data base. Over 200 county demographic, prehospital, and hospital trauma care resource variables were obtained from a variety of sources for multivariate modeling. Bivariate analysis identified candidate variables for multivariate modeling, excluding highly correlated independent variables to avoid problems of collinearity. Multivariate linear regression, logistic regression, and stepwise discriminant analysis were used to determine the relative association of the candidate variables with per capita county trauma death rates. RESULTS: Bivariate analysis identified multiple factors associated with per capita county trauma death rates. These included, among others: county rurality, percentage of unemployment, percentage nonwhite, 911 access, and ALS certified EMS. Per capita trauma death rates were significantly lower in counties with trauma centers compared with counties without trauma centers (4.0 +/- 0.5 and 5.0 +/- 1.1 deaths per 10,000 population, p = 0.0001, respectively). Multivariate analysis demonstrated that the presence of a trauma center in the county and ALS were the best medical system factors predicting decreased per capita county trauma death rates. CONCLUSIONS: This study is unique in utilizing a regional population-based data base of all trauma deaths in a large state to analyze the association of trauma centers and trauma death rates. Multivariate modeling controlling for other county variables demonstrated that the presence of a trauma center and Advanced Life Support training were the best predictors of per capita county trauma death rates. These findings are consistent with the hypothesis that trauma centers decrease trauma death rates. PMID- 1635104 TI - Sonography in blunt abdominal trauma: a preliminary progress report. AB - Evaluation of blunt abdominal trauma is clinically challenging. Diagnostic peritoneal lavage (DPL) and computed tomographic (CT) scanning have become primary diagnostic modalities. We examined the efficacy and role of ultrasonographic (US) studies in the initial abdominal evaluation of blunt trauma patients. Over an 8-month period, patients whose abdominal work-up indicated the need for DPL or CT were evaluated sonographically within the first hour after admission by trauma fellows (PGY-6) with at least 1 hour of theoretical training and 1 hour of practical training. Sonograms considered positive were those showing free peritoneal fluid or organ disruption. Hard copies of the sonograms were evaluated by a staff radiologist without knowledge of the fellows' interpretations or of DPL or CT results. Based on the fellows' interpretation of the real-time sonograms, among the first 163 patients studied were 11 true positive, 146 true-negative, one false-positive, and five false-negative results. Sixteen patients had intra-abdominal injury documented by DPL, CT, or laparotomy. Ultrasonography was 91% sensitive in detecting the presence of hemoperitoneum. Overall, ultrasonography was 69% sensitive, 99% specific, and 96% accurate in diagnosing abdominal injury. We conclude that emergency sonography on admission can serve as a valuable adjunct to the physical diagnosis of clinically significant hemoperitoneum. It is noninvasive, portable, and accurate in determining the need for further diagnostic/surgical intervention. PMID- 1635105 TI - Effect of increased intra-abdominal pressure on mesenteric arterial and intestinal mucosal blood flow. AB - The effects of increased intra-abdominal pressure (IAP) on intestinal blood flow were studied in eight anesthetized pigs. Mesenteric artery blood flow (MABF), intestinal mucosal blood flow (IMBP), tonometric intramucosal pH (pHi), mean BP (MAP), cardiac output (CO), and pulmonary artery wedge pressure (PAWP) were measured as IAP was raised to 10, 20, 30, and 40 mm Hg by infusing lactated Ringer's solution (LR) into the peritoneal cavity. The MAP was kept constant with IV LR. Cardiac output fell slightly from 5.4 +/- 1.1 at baseline to 4.0 +/- 1.2 L/min at an IAP of 40 mm Hg (p less than 0.05). An IAP of 20 mm Hg caused significant decreases in MABF (73% +/- 22% of baseline) (p less than 0.05) and IMBF (61% + 12% of baseline) (p less than 0.05). These changes became progressively greater as the IAP was increased to 40 mm Hg. The pHi fell to 6.98 +/- 0.14 at 40 mm Hg IAP (p less than 0.01), indicating severe mucosal ischemia. Thus increased IAP can cause severe intestinal ischemia, which may be more important than the cardiac, pulmonary, and renal changes usually described. PMID- 1635106 TI - The effect of burn wound size on hemostasis: a correlation of the hemostatic changes to the clinical state. AB - The effect of burn wound size on the activation of fibrinolysis, coagulation, and contact factors was analyzed in 60 thermal injury patients. Blood samples from 47 male patients and 13 female patients, (average age 37 years; range 1.5-70 years) were collected within the first 36 hours and at 5-7 days following injury. The patient population was categorized by percentage of burn (second degree and/or third degree): less than 20%, n = 22; 20%-40%, n = 18; greater than 40%, n = 20. The average percentage of burn was 32% (range, 4%-95%). The mechanism of injury was by flame (25), explosion and flame (19), scald (12), electric (3), or chemicals (1). An associated inhalation injury was present in 12 patients. The overall mortality rate was 13% (8). Sepsis or serious infection occurred in 23% (14) of the patients. On admission, 83% of the patients had normal prothrombin times (PT) and activated partial thromboplastin times (APTT). However, specific hemostatic variables showed marked changes. Admission hemostatic markers that correlated with the severity of injury were: tissue-plasminogen activator (tPA), plasminogen activator inhibitor (PAI), D-dimer (D-di), plasminogen (Plg), proteins C and S (PrC and PrS), antithrombin III (ATIII), thrombin-antithrombin complex (TAT), kallikrein (Kal:c), kinin (Kin), C1 esterase inhibitor (C1Inh), and factor VII clotting and antigen (FVII:c, FVII:ag). These data suggest that during the early course following burn injury, thrombogenicity is increased (TAT increases) because of a decrease in ATIII, PrC, and PrS; and fibrinolysis activation (D-di increases) occurs via an increase in tPA with a p value increase in PAI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635107 TI - "Scoop and run" or stabilize hemorrhagic shock with normal saline or small-volume hypertonic saline? AB - The controversy over a policy of "scoop and run" or stabilizing hemorrhagic shock when evacuation time is short has not yet been settled. Small volumes of hypertonic saline have been suggested as effective therapy when the scoop-and-run policy is adopted. In the present study small-volume hypertonic saline treatment and normal saline treatment of "uncontrolled" hemorrhagic shock (UCHS) in rats were compared with no treatment, which best simulates the scoop-and-run policy. The rats were randomly assigned to three groups. Uncontrolled hemorrhagic shock was induced by 12% resection of the terminal portion of the rats' tails. In group I (n = 13) the animals were untreated. In group II (n = 6) UCHS was treated by administering 41.5 mL/kg 0.9% NaCl (NS). In group III (n = 6) UCHS was treated by administering 5 mL/kg 7.5% NaCl (HTS). Resection of the rats' tails in group I was followed by bleeding of 3.3 +/- 0.3 mL in 15 minutes with a fall in mean arterial pressure (MAP) from 100.9 +/- 7 to 63.5 +/- 5 mm Hg (p less than 0.001). The early bleeding and hemodynamic responses were similar in all three groups. Further blood loss in the first hour in group I was 0.5 +/- 0.2 mL, and MAP rose spontaneously to 73.2 +/- 6 mm Hg (p less than 0.05). The NS infusion in group II was followed by further bleeding of 4.1 +/- 0.9 mL (p less than 0.01) and a further fall in MAP to 53.8 +/- 7 mm Hg (p less than 0.01) after 60 minutes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635108 TI - The clinical significance of myocardial contusion. AB - In an attempt to identify a group of blunt trauma victims with asymptomatic myocardial contusion (MC) who do not benefit from intensive cardiac monitoring, we prospectively divided 336 patients admitted to the SICU with possible MC following blunt trauma in the 6 years prior to January 1990 into three groups: Group 1 (n = 155, age 30.5 +/- 9 years) consisted of those patients admitted for mechanism of injury, J-point elevation, with or without minor chest injury. None developed arrhythmias. Their SICU length of stay (LOS) was 2.41 +/- 0.77 days. Group 2 (n = 43, age 31.5 +/- 10 years) patients had the same admission criteria as the patients in group 1 plus an abnormal emergency department ECG, i.e., arrhythmia, heart block, ischemia. None had cardiac complications. Their SICU LOS was 2.47 +/- 0.94 days. Group 3 (n = 138, age 40 +/- 20 years) patients had four or more rib fxs, a pulmonary contusion, a flail chest, or extra-thoracic injuries or were greater than 60 years of age. All required SICU admission for their non cardiac injuries. Nineteen patients had cardiac complications requiring treatment. None had a cardiac death. Their SICU LOS was 10 +/- 22 days. We conclude that young patients with minor blunt thoracic trauma and a normal or minimally abnormal ECG do not benefit from cardiac monitoring. PMID- 1635110 TI - Focal brain injury results in severe cerebral ischemia despite maintenance of cerebral perfusion pressure. AB - Severe head injury often causes an increase in intracranial pressure (ICP) and decreases in cerebral blood flow (CBF) and cerebral oxygen delivery (CO2del). To determine if this reduction in CBF and CO2del would produce cerebral ischemia and if this reduction would be abrogated by maintaining global cerebral perfusion pressure (CPP), we studied CPP, ICP, CBF, CO2del, cerebral oxygen extraction ratio (CO2ER), and cortical water content (CWC) in a porcine model of focal cryogenic brain injury. Fifteen mature swine were randomized to two groups. The experimental group (n = 7) had a brain lesion and was studied for 24 hours. The control group (n = 8) was instrumented only. Cryogenic injury significantly increased ICP and decreased CBF and CO2del compared with controls. There were no significant differences in CPP between the groups for the entire experiment, and the CPP was well above the ischemic threshold. The CO2ER significantly increased in the first three hours after brain injury. However, CO2ER in experimental animals tended to decrease 12 hours after brain injury and was not significantly different from that in controls. Cryogenic injury significantly increased the CWC in the lesioned hemisphere. These data indicate that focal brain injury results in persistent ischemia despite the normalization of CPP, suggesting that a significant increase in cerebral vascular resistance (CVR) occurs after brain injury. We conclude that in addition to maintenance of CPP, intervention to reduce CVR may be important in the management of brain injury. PMID- 1635109 TI - Local production of interleukin-8 is associated with nosocomial pneumonia. AB - One hundred five (70%) of 151 patients hospitalized in the intensive care unit and undergoing mechanical ventilation had bronchial secretions that tested positive for interleukin-8 within 36 hours of admission. Arterial blood, mixed venous blood, and urine collected simultaneously all tested negative, except for 11 patients admitted with intra-abdominal septic foci. The presence of interleukin-8 in the pulmonary air space early in the course of hospitalization was significantly associated with patients with multiple injuries, the need for greater ventilatory support, the occurrence of pulmonary dysfunction, and a 66% incidence of nosocomial bacterial pneumonia. We conclude that the early local production of interleukin-8 in the lungs is an early marker of pulmonary injury and may be involved in the pathogenesis of nosocomial bacterial pneumonia. PMID- 1635111 TI - The effect of in-line microwave energy on blood: a potential modality for blood warming. AB - The treatment of hypothermia associated with hemorrhage, exposure, or intraoperative intervention continues to represent a challenge for trauma care teams. An innovative technique for combining microwave heating with continuous temperature monitoring into a feedback-controlled system for blood warming has been developed. The effect of microwave warming on the structure and function of blood was compared with that in nonheated controls. Erythrocyte structural integrity (hemolysis) was evaluated by comparing levels of lactate dehydrogenase (LDH), potassium (K+), and plasma hemoglobin (PHGB), and hematocrit (HCT) in heated and nonheated (control) samples of banked red blood cells. Hemoglobin function was evaluated in fresh blood by comparing the P50 and hemoglobin electrophoresis of experimental and control samples. Prewarming temperatures were 3 degrees or 23 degrees C; temperatures after warming were 35 degrees, 37 degrees, or 39 degrees C. The results reflect the percentage of changes for 84 heated and 24 unheated blood samples. There were no statistical differences in any of the biochemical variables measured. The P50 for three heated and three unheated samples was 30.7 +/- 1.2 and 30.5 +/- 0.9 mm Hg (p greater than 0.05). There were no changes in the hemoglobin electrophoretic patterns in experimental or control samples. This system is designed to deliver microwave energy in a uniform and controlled manner, overcoming the limitations of conventional microwave ovens that in the past caused local overheating and subsequent hemolysis when used for blood warming. The structural and functional integrity of erythrocytes after microwave warming indicate the safety and effectiveness of this technique. PMID- 1635112 TI - Early criteria predictive of prolonged mechanical ventilation. AB - This study was performed to determine if prolonged mechanical ventilation (MV) could be predicted by objective clinical variables present at 48 hours after MV was instituted. During a 3-month period, 49 (54%) of 91 mechanically ventilated surgical intensive care unit patients required MV for 2 or more days. Twelve (24%) of these patients died. Patients requiring 2-13 days of MV had significantly lower alveolar-arterial oxygen gradients (PAO2 - PAO2), PEEP, and FIO2 on MV day 2 compared with patients with MV greater than or equal to 14 days. PAO2 - PAO2 greater than or equal to 175 mm Hg on day 2 in patients without chronic obstructive pulmonary disease (COPD) was 60% sensitive and 91% specific for MV greater than or equal to 14 days. In survivors, a day-2 PAO2 - PAO2 greater than or equal to 175 mm Hg (without COPD) or a GCS score less than or equal to 9 had a 91% positive predictive value and a 96% negative predictive value for MV greater than or equal to 14 days. We conclude that mechanical ventilation for 14 or more days can be accurately predicted at 48 hours after the institution of ventilatory support by these objective criteria. PMID- 1635113 TI - Radiographic evaluation of adult patients with blunt renal trauma. AB - Recent reports in the literature suggest that radiographic evaluation of the normotensive blunt trauma patient with microscopic hematuria is no longer necessary. Several facilities, however, including ours, continue to perform excretory urography (IVP) routinely in this setting. To evaluate further whether this practice is indicated, we retrospectively reviewed the records of 317 adults who presented to our facility between May 1986 and December 1989 after blunt trauma with resultant microscopic hematuria but no shock. All patients were radiographically assessed with an IVP. Of the 317 studies 29 (9%) had an abnormal result, including 28 with renal contusion and 1 with a nonfunctioning kidney (in which case further evaluation revealed a congenitally absent kidney). No significant urological injury was identified. Thus, no injury would have been missed if a policy of observation had been followed in these patients. Our data support other reports in the literature that radiographic staging is not necessary in the adult blunt trauma patient with microscopic hematuria but no shock. PMID- 1635114 TI - Angiographic embolization of renal stab wounds. AB - Nonoperative management of renal stab wounds following complete radiographic assessment has become an accepted if not preferred therapeutic option. Selected injuries, however, including renal artery branch injuries, often require surgical intervention and result in partial or total nephrectomy. We report our experience with 16 renal branch arterial injuries secondary to street stabbing during the last 10 years that were managed with angiography and embolization techniques. Angiography with embolization was the initial treatment in 11 patients, while 5 had undergone emergency surgical intervention initially because of hemodynamic instability. Subsequently, gross hematuria recurred in the latter 5 patients and they were managed angiographically. Overall, 14 of 16 patients had prompt hemostasis documented either on the post-embolization angiogram or by clinical assessment. In 2 patients bleeding was increased but partial nephrectomy ultimately was required. Complications included nontarget embolization in 2 patients: 1 subsequently had hypertension and 1 had no untoward effect as a result of this complication. We conclude that angiography with transcatheter embolization techniques provides a safe and effective means of managing renal artery branch injuries secondary to stab wounds. PMID- 1635115 TI - Microscopic venous infiltration as predictor of relapse in renal cell carcinoma. AB - In a retrospective analysis at a single institution we evaluated the significance of various pathological phenomena on the disease-free survival of patients with radically resected renal cell carcinoma. Parameters considered were tumor extension (pT stage) according to the International Union Against Cancer, tumor invasion into the renal vein or vena cava (V stage), standard histological grading (G stage), nuclear grading (F stage) and microscopic venous infiltration. The pT stage had a significant impact on disease-free survival (p = 0.0004) of patients with radically resected tumors, as did G stage (p = 0.0001) and F stage (p = 0.002). In contrast to some previously reported results tumor extension to the renal vein and vena cava showed no influence on disease-free survival (p = 0.077). On the other hand, microscopic venous infiltration, defined as local tumor infiltration through all vessel structures including the endothelial layer leading to a free tumor extension into the vessel, had a significant impact on disease-free survival (p less than 0.0001). When stratifying either tumor size or nuclear differentiation against microscopic venous infiltration, the latter retained a superior influence on disease-free survival (p = 0.01 and p = 0.0079, respectively). We conclude that microscopic venous infiltration is the most important predictor of relapse in renal cell carcinoma. PMID- 1635116 TI - Ureteroscopic treatment of urothelial carcinoma of the ureter and renal pelvis. AB - From June 1987 to September 1990, 12 patients were evaluated for ureteroscopic treatment of upper urinary tract neoplasms. Four patients were not considered candidates because of technical reasons. Each of these patients was treated by nephroureterectomy. A total of 8 patients underwent ureteroscopic therapy with a neodymium:YAG laser 1 to 11 times (median 2) for the treatment of 3 proximal ureteral or pelvic lesions and 7 distal ureteral lesions. One patient had local progression and 1 failed subsequent laser treatment for technical reasons. Both of these individuals were salvaged with an operation. Three patients were without recurrence for 15, 21 and 36 months. Two patients had multiple superficial local recurrences and continue to be managed endoscopically without local progression for 12 and 32 months. One patient was asymptomatic 16 months after treatment but he has refused followup evaluation. Of 7 patients with ureteral tumors who were believed to be candidates for endoscopic therapy 5 have had the tumors controlled by this method of treatment. Only 1 renal pelvic tumor has been successfully treated. Most patients with tumors in the renal pelvis are not candidates for rigid endoscopic therapy because of the tumor size and location. In selected individuals ureteroscopic laser treatment of upper urinary tract transitional cell carcinoma can achieve local control with renal preservation. PMID- 1635117 TI - The double-J ureteral stent: in vivo and in vitro flow studies. AB - Although most ureters can now be stented, the rate of ureteral obstruction from extrinsic compression remains relatively high. To illuminate the mechanisms of obstruction in these patients we performed 20 in vivo pressure-flow investigations in 14 patients with indwelling ureteral Double-J stents. All patients had a percutaneous nephrostomy tube in place. Our investigations revealed proper drainage to the bladder in 17 of the 20 studies at an average renal pelvic pressure of 19.9 cm. water. Vesicorenal reflux was noted at an average bladder pressure of 20 cm. water in 17 studies. Three stents appeared to be obstructed. They showed no drainage to the bladder but also no reflux. To evaluate the in vivo results we then performed an in vitro study of pressure-flow characteristics under conditions simulating ureteral obstruction. At physiological flow rates different ureteral stents showed no major differences in pressure-flow characteristics. With compression and kinking, flow resistance in softer stents was notably greater than in hard stents. Therefore, we believe that in patients with suspected extrinsic compression of the ureter hard Double-J stents should be used. Vesicorenal reflux appears to be a reliable predictor of stent function. PMID- 1635118 TI - Metallic Wallstents: a new therapy for extrinsic ureteral obstruction. AB - Self-expanding metallic stents, frequently used in interventional radiology, were implanted into 15 obstructed ureters in 12 patients. The cause of obstruction was lymph node metastases of different malignant tumors or direct tumor compression of the ureter. Followup in 12 patients was 3 to 31 weeks. Immediately after implantation all stents drained well. During the initial 4 weeks slight obstruction occurred due to hyperplasia of regenerating urothelium. The stents were fully incorporated into the ureteral wall 8 weeks after implantation, they were covered by smooth epithelium and the hyperplasia had disappeared. Complications were hemorrhagia in 1 patient and incrustation in 2. No infection was observed. Complications due to the tumor were obstruction distal to the stent in the presence of a widely open catheter in 3 patients. Early results are presented. Late results are not yet available. The method seems to be minimally invasive and easy to perform. PMID- 1635119 TI - Balloon cystoscopy with neodymium:YAG laser. AB - We performed balloon cystoscopy for the diagnosis of gross hematuria as well as for the treatment of bladder tumor using the neodymium:YAG laser. Animal experiments were done to evaluate the efficacy of laser irradiation through the balloon, which proved to have the same effect as conventional laser irradiation. A total of 40 patients with bladder diseases was observed and treated by balloon cystoscopy, and the results were examined comparatively. Even with gross hematuria the structure of the mucosa and the tumor could be observed in detail without irrigating the inside of the bladder. Most bladder tumors were successfully treated with laser irradiation through the balloon through the optic lens system. Therefore, balloon cystoscopy appears to be a useful endoscopic modality in neodymium:YAG laser surgery for the treatment of bladder tumor. PMID- 1635120 TI - Home screening for hematuria: results of a multiclinic study. AB - The majority of urinary tract tumors cause bleeding in the urine. A program designed to detect hematuria before it is grossly apparent may contribute to earlier detection and more successful treatment of these malignancies. To test this hypothesis a hematuria home screening study was conducted. A total of 1,340 healthy men 50 years old or older used chemical reagent strips for 14 consecutive days to test the urine. Of the men 283 (21.1%) had at least 1 episode of hematuria. Of the 192 hematuria positive men who received a complete urological evaluation 16 (8.3%) had urological cancers and 47 (24.5%) had other hematuria causing diseases that required immediate treatment. The quantity and frequency of hematuria were not related to disease severity. A hematuria home screening regimen is feasible and economical, and may promote the early detection of urinary tract cancers and other diseases in men more than 50 years old. PMID- 1635121 TI - The predictive value of flow cytometry and urinary cytology in the followup of patients with transitional cell carcinoma of the bladder. AB - To determine the predictive value of flow cytometric deoxyribonucleic acid (DNA) ploidy and urine cytology in patients with superficial transitional cell carcinoma of the bladder, a retrospective analysis was performed on 181 patients who presented for evaluation of presumed superficial transitional cell carcinoma of the bladder. Of the patients 91 were confirmed to have superficial transitional cell carcinoma and were systematically followed with cystoscopy, flow cytometry and urine cytology from 1984 until 1989. They underwent 637 evaluations (mean 7 evaluations per patient). At initial evaluation, flow cytometry had 81% sensitivity and 57% specificity, while urine cytology was 75% sensitive and 94% specific. During the followup flow cytometry was 76% sensitive and 36% specific. Urine cytology was less sensitive (40%) but more specific (81%) than flow cytometry in followup evaluation. These results were similar whether intravesical chemotherapy or bacillus Calmette-Guerin was administered. To ascertain whether false positive flow cytometry represented early detection of recurrent transitional cell carcinoma not apparent at cystoscopy, patients with positive flow cytometry and urine cytology were followed longitudinally. False positive flow cytometry and urine cytology were equally predictive of recurrent transitional cell carcinoma progressively with time. However, for any given examination flow cytometry was more likely to detect and predict recurrent transitional cell carcinoma. At 4 years the bladder transitional cell carcinoma incidence for false positive flow cytometry and urine cytology was 87% and 84%, respectively. PMID- 1635122 TI - Adjuvant chemotherapy of recurrent superficial transitional cell carcinoma: results of a European organization for research on treatment of cancer randomized trial comparing intravesical instillation of thiotepa, doxorubicin and cisplatin. The European Organization for Research on Treatment of Cancer Genitourinary Group. AB - A total of 356 patients with recurrent superficial transitional cell carcinoma of the bladder was entered in a randomized clinical trial to compare intravesical thiotepa, doxorubicin and cisplatin with respect to the recurrence rate and disease-free interval. After complete transurethral resection of all visible lesions, the drugs were administered weekly for 4 weeks and monthly for 11 months. The recurrence rates per year were 0.50 for thiotepa, 0.54 for doxorubicin and 0.58 for cisplatin. Of 266 patients (mean followup 41 months) 35 reported an increase in T category and 19 of them had distant metastases. No association between treatment and progression was noted. Thus, there is no difference among treatments with respect to efficacy. However, severe anaphylactic reactions were observed in the cisplatin arm and chemical cystitis was more frequently reported in patients who received doxorubicin. PMID- 1635123 TI - Advanced bladder cancer (stages pT3b, pT4a, pN1 and pN2): improved survival after radical cystectomy and 3 adjuvant cycles of chemotherapy. Results of a controlled prospective study. AB - A total of 49 bladder cancer patients with tumor stages pT3b, pT4a and/or pelvic lymph node involvement without microscopic or macroscopic evidence of residual tumor was randomized into 2 comparative groups: the chemotherapy group was to receive 3 adjuvant cycles of methotrexate, vinblastine and cisplatin plus doxorubicin (M-VAC) or epirubicin (M-VEC) after radical cystectomy. The control group received no additional treatment. The protocol was activated in May 1987. Patient recruitment was concluded in December 1990 because an interim analysis of the 49 randomized patients revealed a significant prognostic advantage in favor of 26 patients randomized to the chemotherapy group compared to 23 in the control group (p = 0.0015, log rank test for relapse-free survival curves). Of the 26 patients randomized for adjuvant chemotherapy 18 were treated with M-VAC or M-VEC (3 cycles in 16 patients and 2 cycles in 2). Of the remaining 8 patients 7 refused chemotherapy before or during cycle 1 and 1 received chemotherapy without cisplatin because of impaired renal function. An update of the patients in August 1991 revealed a further increase in the prognostic difference between the 2 trial arms (p = 0.0012). Of 18 patients who received treatment with M-VAC or M-VEC only 3 have had tumor progression to date compared to 18 of 23 patients in the control group. Further statistical analysis of the data was performed on the basis of Cox's regression model, incorporating various criteria as explanatory variables, including patient sex and age, pT stage and number of involved lymph nodes. This multivariate analysis revealed a significant decrease in the risk of tumor recurrence (p = 0.0007, 2-sided) after adjuvant chemotherapy. The number of lymph nodes involved was also of prognostic significance (p = 0.0028, 1-sided). The results indicate that the survival time after radical cystectomy can be prolonged considerably by adjuvant polychemotherapy in cases of locally advanced bladder carcinoma. Fortunately, all of these conclusions are not affected by switching from an intent-to-treat analysis to an analysis of the therapy actually performed. The p values obtained from the latter are 0.0005 (log rank test) and 0.0001 (Cox model with the same set of additional regressors). PMID- 1635124 TI - Treatment of recurrent urethral stricture by internal urethrotomy and intermittent self-catheterization: a controlled study of a new therapy. AB - A controlled study of the effect of treatment of recurrent urethral stricture by internal urethrotomy followed by clean intermittent self-catheterization for 3 months is reported. There were 28 men (median age 70 years, range 18 to 75) allocated to internal urethrotomy and clean intermittent self-catheterization for 3 months (treatment group) and 33 (median age 76 years, range 36 to 87) were randomized to undergo internal urethrotomy only (observation group). The groups were comparable in terms of patient age, etiology of the primary stricture, number of recurrences, length and site of the actual stricture, and preoperative maximum flow rate (p less than 0.01). After termination of the treatment all patients from both groups were evaluated by uroflowmetry 2, 4, 6 and 12 months later, and a new recurrence was defined as a maximum flow rate of less than 10 ml. per second (micturition volume greater than 100 ml.) and a characteristic flow curve. From the treatment group 23 patients could be assessed: 2 had discontinued clean intermittent self-catheterization due to urethral hemorrhage, 2 died during the observation period and 1 was lost to followup. From the observation group 28 patients were assessable: 3 died during the observation period and 1 was lost to followup. Treatment results were not significantly different (p less than 0.01). Of the patients in the treatment and observation groups 78% and 82%, respectively, had a new stricture. The median interval for this to occur was 4 months for both groups. Since no patient had clinical signs of stricture during clean intermittent self-catheterization, we conclude that for the treatment of recurrent urethral stricture clean intermittent self catheterization following internal urethrotomy should be continued for a long duration, possibly permanently. PMID- 1635125 TI - The change of urinary 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto prostaglandin F1 alpha in arteriogenic impotence. AB - Thromboxane A2 is a potent vasoconstrictor and a stimulus of platelet aggregation, which may contribute to hypercoagulability. The prostacyclin, prostaglandin I2, has exactly the opposite effect. Measurement of the major urinary metabolites, 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha (prostaglandin F1 alpha) by radioimmunoassay can accurately reflect in vivo the biosynthesis of thromboxane A2 and prostaglandin I2, respectively. Group 1 consisted of 60 patients less than 50 years old. The mean urinary 11-dehydro thromboxane B2 level of 3 patients with arteriogenic impotence was significantly greater than that of the 57 control volunteers: 2.66 +/- 0.65 versus 1.74 +/- 0.56 (plus or minus standard deviation) ng./mg. creatinine (p = 0.008). The prostaglandin F1 alpha levels for the patients and controls were 32.74 +/- 8.45 and 37.58 +/- 16.55 ng./mg. creatinine, respectively, which was not significantly different (p greater than 0.05). Group 2 consisted of 96 patients 50 years old or older. The 11-dehydro-thromboxane B2 concentration in the urine was 1.83 +/- 0.58, 2.54 +/- 1.12 and 1.91 +/- 0.73 ng./mg. creatinine in the 47 normal control volunteers, 20 patients with arteriogenic impotence and 29 with arteriogenic impotence plus intracavernous injection of 20 micrograms prostaglandin E1, respectively. The arteriogenic impotence group showed the significantly highest level among the 3 groups (p = 0.0025). Also, the urinary prostaglandin F1 alpha levels in these patients were 45.71 +/- 36.3, 57.71 +/- 35.53 and 59.30 +/- 45.08 ng./mg. creatinine, respectively, which was not significantly different (p greater than 0.05). For the 13 patients with arteriogenic impotence (group 3) we compared the urinary 11-dehydro-thromboxane B2 and prostaglandin F1 alpha levels before and after intracavernous injection of prostaglandin E1 by using a paired t test. The results showed that the change in 11-dehydro-thromboxane B2 levels was 2.78 +/- 1.09 versus 1.99 +/- 0.75 ng./mg. creatinine, which was significantly different (p = 0.005), whereas that for prostaglandin F1 alpha was 62.30 +/- 40.41 versus 58.86 +/- 44.26 ng./mg. creatinine, with no significant difference (p greater than 0.05). Our findings suggest that urinary 11-dehydro-thromboxane B2 may have an important role in the diagnosis and treatment of arteriogenic impotence. PMID- 1635126 TI - The value of increased end diastolic velocity during penile duplex sonography in relation to pathological venous leakage in erectile dysfunction. AB - In 58 patients 23 to 71 years old (mean age 49.5 years) with suspected vasculogenic erectile dysfunction diagnosed on the basis of repeated negative reactions to intracavernous pharmacological stimulation (rigidity less than 60% when measured with the RigiScan* device) pharmacocavernosometry and duplex Doppler measurements were performed. The end diastolic velocity in the 24 patients without venous leakage ranged from 0 to 21 cm. per second (mean 7.5 +/- 6.3, standard deviation). The end diastolic velocity in the 34 patients with venous leakage ranged from 0 to 26 cm. per second (mean 9.0 +/- 6.7). In 23 of the 58 patients a peak systolic velocity of less than 25 cm. per second was found, which is an indication of arterial disease. Of 35 patients with a normal peak systolic velocity 15 were in the group without and 20 were in the group with leakage. In the group with a normal peak systolic velocity no statistically significant difference was found in end diastolic velocity between patients with and without leakage. We conclude that the end diastolic velocity during color Doppler analysis of patients with negative reactions on intracavernous pharmacological stimulation does not provide a good indication of potential pathological venous leakage. PMID- 1635127 TI - The value of dynamic color duplex scanning in the diagnosis of venogenic impotence. AB - To determine the value of color duplex scanning in the diagnosis of venogenic impotence we examined 53 patients. The control population consisted of 26 psychogenically impotent men and 8 normal potent men who all had a firm erection after pharmacological stimulation. There was no significant difference in the values of duplex parameters between these 2 groups. The venous leak population was characterized by a bad erectile response to pharmacological stimulation despite a good arterial compliance and by a persistent diastolic flow as shown by duplex scanning. There was a significant difference with the control population for the parameters of resistance index after 10 minutes (p = 0.001), minimal resistance index (p = 0.016) and corporeal volume increase (p = 0.010). There was a good correlation between the results of duplex scanning and those of pharmacocavernosography-pharmacocavernosometry (93%). We conclude that dynamic color duplex scanning can be used as a screening procedure to diagnose significant venous leakage in an objective manner with the resistance index. PMID- 1635128 TI - Current urological practice: routine urological examination and early detection of carcinoma of the prostate. AB - With the increasing incidence of carcinoma of the prostate, the interest in early diagnosis through screening has dramatically increased. Several organizations, including the American Urological Association (AUA) and the American Cancer Society, have promulgated recommendations on suggested early detection methods. To determine the current practice patterns of United States urologists, a survey was sent to a random sample of 10% of all urologist members of the AUA. The survey was designed to determine what are current recommendations for an annual urological checkup for older men, what tests should be included in screening for carcinoma of the prostate and what age groups of men should undergo prostate cancer screening. A total of 562 surveys was returned, constituting a 4.7% sample of all urologist members of the AUA. The use of digital rectal examination was unanimously recommended for the urological examination as well as for prostate cancer detection. Prostate specific antigen was recommended by a majority of respondents for both situations. Screening was recommended for men ages 50 to 80 years. Demographic factors had a significant role in clinical recommendations by urologists. PMID- 1635129 TI - Frequency and location of extracapsular extension and positive surgical margins in radical prostatectomy specimens. AB - Positive surgical margins have been reported with disturbing frequency in radical prostatectomy specimens and may portend an increased risk of eventual treatment failure. We determined the location of any cancer, extracapsular extension and positive surgical margins in 144 consecutive step-sectioned radical prostatectomy specimens. Of the 46 stage A cancer patients 98% had residual cancer in the prostate after transurethral resection and in 76% cancer was found posteriorly in the gland. Extracapsular extension was identified in 10 patients (22%): anteriorly in 5, posterolaterally in 5 and on the most apical transverse section in 4. Positive margins were found in 10 patients (22%) and half of these occurred posterolaterally. Of the 98 stage B cancer patients tumor was located posteriorly in 97%. Extracapsular extension was found in 62 patients (63%) and in 87% of these it was located posterolaterally. Positive margins were found in 23%, most commonly in the posterolateral and rectal areas (57% and 26%, respectively), and in more than half of these the positive margin resulted from incision into the capsule. In 18 of the 144 patients (13%) a single positive surgical margin was the only pathological indicator of treatment failure and half of these occurred in the area of the neurovascular bundle. Some of these patients with extraprostatic tumor might have been cured if wide excision of the neurovascular bundle had been performed. Overemphasis on preservation of potency during radical prostatectomy may leave some patients with persistent local disease. PMID- 1635130 TI - Ultrasound for detecting Schistosoma haematobium urinary tract complications: comparison with radiographic procedures. AB - Chronic infection with Schistosoma haematobium primarily causes urinary tract complications. These lesions are often silent or ignored and not detected until irreversible changes have occurred. However, early chemotherapy can prevent progression and usually reverse all but the more severe abnormalities. Recently, abdominal ultrasound has been shown to be an inexpensive, portable and safe means of detecting schistosomal morbidity. A prospective study was performed on 40 patients comparing abdominal radiography, excretory urography (IVP), cystoscopy and ultrasound to detect urinary tract morbidity due to S. haematobium infection. Ultrasound was as sensitive as an IVP in detecting bladder masses, hydronephrosis and renal stones. It detected hydroureter less frequently (sensitivity 62.5%) than an IVP but visualized this lesion and hydronephrosis in some patients with nonfunctioning kidneys. Ultrasound demonstrated bladder stones as well as an x ray but it detected bladder wall calcification with less sensitivity (65%) and was much less sensitive (12.5%) for detecting ureteral stones. PMID- 1635131 TI - Stepladder incision technique for lengthening of bowel mesentery. AB - A tension-free bowel anastomosis is essential when bowel segments are used in reconstructive urological procedures. A safe and effective technique is described to lengthen the mesenteric vascular pedicle. Serial incisions are made in the mesenteric peritoneum horizontally, perpendicular to the vascular plane on both sides of the mesentery. This technique has provided up to 3 cm. of additional length without complication in 3 cases. PMID- 1635132 TI - A modified surgical retractor blade for radical retropubic prostatectomy and retropubic surgery. PMID- 1635133 TI - A simple test for the detection of intraoperative rectal injury in major urological pelvic surgery. AB - We describe our experience with a simple inexpensive test with 2 practical uses: 1) to detect unrecognized intraoperative rectal injury and 2) to assess the adequacy of repair of rectal injuries. PMID- 1635134 TI - Detrusor function in suprasacral spinal cord injuries. AB - A total of 21 patients with chronic, stable suprasacral spinal cord injuries underwent a comprehensive neurological evaluation. A second lumbosacral lesion was excluded. The urodynamic findings were relatively constant as 95% of the patients showed detrusor hyperreflexia with elevated pressures, sphincteric dyssynergia and a competent bladder neck during the filling phase. The urodynamic findings of unexpected detrusor function in high spinal cord injury, for example areflexia and hypocontractility, should raise the clinician's suspicion that there is a lesion or dysfunction involving the sacral cord. PMID- 1635135 TI - Results of the renewed extravesical reimplant for surgical correction of vesicoureteral reflux. AB - In 1987 Firlit et al described their results using Hodgson's technique of the modified extravesical Gregoir-Lich procedure. They coined the term detrusorrhaphy or extravesical ureteral advancement to describe this technique. During the last 4 years we performed this reimplantation on 211 ureters in 132 patients. Of the patients 79 had unilateral and 53 had bilateral procedures. Included were 6 megaureters requiring ureteral tailoring and 9 uncomplicated duplications. All but 1 patient were cured of reflux. No postoperative obstruction was encountered. Our results indicate that this is an excellent procedure to repair vesicoureteral reflux with minimal morbidity and short hospital stay. PMID- 1635136 TI - Urodynamic dysfunction in walking myelodysplastic children. AB - We evaluated urodynamically and radiologically 54 children with myelodysplasia and neurological deficits at or below the S1 level. Baseline urodynamic testing was normal in 13 patients (24%), while 12 (22%) had an upper motor neuron and 13 (24%) had a lower motor neuron type of dysfunction. A total of 7 patients (13%) had a mixed upper and lower motor neuron type, and 9 (17%) had only lower motor neuron dysfunction of the urethral sphincter with a normally contractile bladder. Followup studies varying in time from 1 month to 10 years showed a changing neurourological lesion in 29 patients (54%): 25 deteriorated while 4 improved. Of the 54 children 20 had hydronephrosis and/or vesicoureteral reflux. Incontinence was the major problem in 41 patients (75%), and was managed initially with pharmacological agents and/or clean intermittent catheterization, with 9 of the 41 eventually requiring surgery. Urodynamic assessment reveals a variable picture that does not correlate well with the apparent neurological examination. Despite the low level of the neurological deficit, many children may be at risk for urinary tract deterioration. These findings emphasize the importance of continuous surveillance and appropriate management in this group of myelodysplastic children who have the greatest potential for a normal life. PMID- 1635137 TI - The management of the neuropathic bladder in adolescents with imperforate anus. AB - The management of 58 patients born with an imperforate anus who presented to the urology service and who are currently 18 years old or older is discussed. Of the 44 patients with a high imperforate anus 43 were treated by a rectal pull-through and 1 by an anal cut back procedure, while an anal cut back procedure was used in all 14 children with a low imperforate anus. A total of 32 children (55%) had a neuropathic bladder (hyperreflexic in 29 and atonic in 3). A spinal deformity was present in 72% of the hyperreflexic group but not in the atonic group. Vesicoureteral reflux occurred in 41% of the patients, two-thirds of whom had a neuropathic bladder. A total of 30 children had an associated genital anomaly and 27 had an upper tract anomaly. Nineteen children underwent an operation for the neuropathic bladder, with modern reconstructive methods involving substitution or augmentation cystoplasty, supplemented with self-catheterization, being superior to older methods with regard to continence. The incidence of a neuropathic bladder in these children is high in both operative groups but it is usually associated with a spinal deformity and unlikely to be iatrogenic in nature unless proved to be of lower motor neuron origin. Early operative management is advised to achieve continence and minimize renal impairment. PMID- 1635138 TI - Perforation of the gastric segment of an augmented bladder secondary to peptic ulcer disease. AB - Gastrocystoplasty consists of bladder augmentation using part of the gastric body. We describe a child in whom peptic ulcer disease developed in the gastric portion of the bladder, with subsequent perforation of the ulcer. Chronic renal failure, hypercalcemia and oliguria are potential ulcerogenic conditions commonly present in patients with gastrocystoplasty. Perforation of the ulcer is a potentially fatal complication. Periodic cystoscopy and prophylactic treatment with hydrogen blockers and alkalization of the urine should be considered in patients with those risk factors. PMID- 1635139 TI - Ileal nipple for continence in cloacal exstrophy. AB - Since 1985, 7 children 2 to 17 years old with urinary incontinence from cloacal exstrophy underwent bladder augmentation and creation of a small bowel nipple at the bladder outlet. There were 3 genetic female and 4 genetic male patients being reared in the female role. In 3 early cases augmentation was done with small bowel, while gastric augmentation was used in 3 later cases and 1 had both types. Six patients became completely dry and they empty by intermittent self catheterization. In the youngest patient the operation failed because the nipple became infarcted and disappeared. Reoperation will be performed after at least 1 year has passed. In cloacal exstrophy if there is insufficient local tissue to create a bladder neck and urethra, a reversed, catheterizable bowel nipple may be an option to consider. PMID- 1635140 TI - Traumatic priapism in a child: evaluation with color flow Doppler sonography. AB - We report a case of nonischemic priapism in an 11-year-old boy that occurred after blunt perineal trauma. Color flow Doppler sonography ruled out ischemic priapism and proved itself valuable as part of the emergency diagnostic evaluation of priapism in childhood. PMID- 1635141 TI - Posttraumatic arterial priapism in a 7-year-old boy: successful management by percutaneous transcatheter embolization. AB - Priapism may be classified as the classical veno-occlusive form or the more recently described high flow, arterial type. We report a case of posttraumatic arterial priapism in a 7-year-old boy. The successful management with percutaneous transcatheter embolization of the internal pudendal artery is described. PMID- 1635142 TI - Unilateral hydroureteronephrosis caused by abdominoscrotal hydrocele. AB - Abdominoscrotal hydrocele is extremely rare in children. A case is presented of an unusually large abdominoscrotal hydrocele in a child, with secondary right hydroureteronephrosis due to contiguous pressure and right cryptorchidism. This entity, although unusual, should be considered in the differential diagnosis of a lower abdominal mass in children, as well as a cause of hydroureteronephrosis. Diagnosis is made with ultrasound, computerized tomography and occasionally excretory urography. Complete surgical excision through a groin incision is recommended, but optional inguinoabdominal or abdominal incisions have been reported. After surgical removal, healing is usually complete, including regression of the hydroureteronephrosis. PMID- 1635143 TI - Repair of an autotransplant renal artery aneurysm: case report and literature review. AB - We report the successful repair of a renal artery aneurysm involving the autotransplanted kidney of a 25-year-old hypertensive woman. The risk factors for renal artery aneurysm rupture, and the relationships between hypertension and renal artery aneurysms are presented. PMID- 1635144 TI - Late onset renal allograft anastomotic pseudoaneurysm with absent Doppler signal. AB - A large extrarenal pseudoaneurysm, originating from the arterial anastomosis of a renal allograft, occurred spontaneously 7 years after transplantation in a 29 year-old diabetic patient. Although the scintigraphic examination was diagnostic of a pseudoaneurysm, pulsed Doppler and color coded Doppler ultrasound failed to demonstrate a Doppler signal, suggesting erroneously a nonvascular fluid collection. The role of scintigraphy combined with duplex ultrasound in this rare but potentially fatal complication of renal transplantation is discussed. PMID- 1635145 TI - Late development of renal carcinoma in allograft kidney. AB - The Cincinnati Transplant Tumor Registry recorded 169 cases of renal carcinoma developing in transplant recipients. The great majority of these cases were of primary renal cell carcinoma developing in the recipient native kidneys. Renal carcinoma developing de novo in the renal allograft occurred 17 times, with a maximal interval to clinical development of 85 months after transplantation. The development of multicentric renal cell carcinoma in an allograft 156 months after transplantation is described. The 24-year-old white male recipient with Alport's syndrome received a cadaver renal allograft from a healthy 27-year-old black man who had died of a cerebral hemorrhage in 1977. At 13 years after transplantation the recipient had upper abdominal pain. Ultrasound revealed 2 incidental renal masses and a renal cyst in the allograft. Partial nephrectomy confirmed the presence of multicentric renal carcinoma. The graft was left in situ and immunosuppression was maintained. The recipient continued to do well with no evidence of disease 1 year postoperatively. Deoxyribonucleic acid banding demonstrated that the tumor and recipient blood were of different patterns. PMID- 1635146 TI - Transitional cell carcinoma of the kidney with vena caval involvement: report of 3 cases and a review of the literature. AB - Vena caval tumor thrombus in association with transitional cell carcinoma of the kidney is uncommon, with only 9 cases having been reported to our knowledge. We report 3 additional cases and review this subject with particular attention to symptoms, radiographic evaluation and the importance of early diagnosis. PMID- 1635147 TI - A late manifestation of testicular seminoma in the bladder in a renal transplant recipient: a case report. AB - An unusual case is presented of a renal transplant recipient on immunosuppressive medication who underwent orchiectomy for a testicular seminoma. Since the surgical resection plane showed seminoma cells, radiotherapy was applied to the para-aortic and inguinal regions. Tumor recurred in the bladder 3 years later as demonstrated by urine cytology and later by bladder biopsies. After chemotherapy, repeated bladder biopsies were normal and a complete remission was achieved. The possible metastatic pathways are discussed. PMID- 1635148 TI - Trifurcation of the urethra: a case report. AB - Trifurcation of the anterior urethra is an uncommon anomaly. We present a case of trifurcation of the anterior urethra with pelvic ectopia of the right kidney and complete left ureteral duplication. PMID- 1635150 TI - Total prostatoseminal vesiculectomy in the treatment of debilitating perineal pain. AB - Persistent perineal pain, unresponsive to antibiotics and analgesia, sufficient to produce an inability to function in any work or social environment is occasionally encountered. A total of 5 such patients underwent total prostatoseminal vesiculectomy: 3 experienced complete relief of the pain and 1 experienced symptomatic relief to the extent that he ranks the residual discomfort as 1 on a scale of 1 to 10. The remaining patient had complete absence of pain for approximately 4 months but thereafter mild, intermittent proximal urethral discomfort developed during voiding. Total prostatoseminal vesiculectomy may be occasionally applicable in the patient disabled by chronic perineal pain. We believe that psychiatric evaluation and concurrence should be a preoperative prerequisite. PMID- 1635149 TI - Actinomycosis associated with pilonidal sinus of the penis. AB - We report a case of actinomycosis associated with a penile pilonidal sinus. This association does not appear to have been described previously. We recommend the submission of biopsies of unusual lumps in the genital region (fresh biopsies for bacteriological examination and fixed biopsies for histomorphological assessment). PMID- 1635151 TI - Re: The no-scalpel vasectomy. PMID- 1635152 TI - Radioimmunodetection of human bladder tumor xenografts in nude mice with radiolabeled monoclonal antibodies. AB - The tumor targeting potential of two monoclonal antibodies (mAbs) reacting with growth-regulated surface glycoproteins of human bladder cancer was investigated. The mAb T16 reacts more intensely with stationary cells while the mAb T43 is preferentially reactive with exponentially growing cells. The test target was T24 human bladder cancer cells grown subcutaneously in 30 nude mice. Controls for tumor specificity were human lung cancer cells grown on the contralateral side. Purified mAb's T16 and T43, and Om5, a non-reactive control, were radiolabeled with 131-Iodine and injected intravenously in doses ranging from 50 to 300 microCi in tumor-bearing animals. Consistent images of the bladder cancer xenografts were obtained at 48 and 72 hours with tumors as small as 0.1 gm. High resolution tumor images were obtained only with the reactive antibodies and according to their in vitro specificity. These results demonstrate that the two mAbs T16 and T43 can specifically and sensitively localize human bladder cancer cells in vivo. PMID- 1635153 TI - Epidermal growth factor: receptor binding and effects on the sex accessory organs of sexually mature male mice. AB - The role of epidermal growth factor (EGF) in maintaining the integrity of the male sex accessory glands was investigated in the mouse. In the sexually mature male C3H mouse, EGF levels were highest in the submandibular gland, followed by the seminal vesicles and the prostate. Twenty eight days after sialoadenectomy (Sx), EGF fell below detectable limits in the serum and in the seminal vesicles. However, the prostate still retained 22% of its immunoreactive EGF. There was a seven-fold increase in serum testosterone after sialoadenectomy. Despite this drastic rise in testosterone, both prostatic and seminal vesicular weights were reduced, serum levels of LH were suppressed only by 37% and FSH levels were not altered. All these changes were abolished by the simultaneous administration of exogenous EGF at 100 micrograms./kg./day for 28 days. Both prostatic and seminal vesicular membranes contained binding sites for 125I-EGF. Binding was maximal after one hour of incubation at room temperature. Two classes of binding sites were shown for either organ (Kd = 1.2 nM, n = 56 fmol/mg. and Kd = 74 nM, n = 540 fmol/mg. for prostate; Kd = 0.9 nM, n = 29 fmol/mg. and Kd = 93 nM, n = 150 fmol/mg. for seminal vesicle). The binding of 125I-EGF was displaced by excess EGF and TGF-alpha but not by insulin, ILGF-2 and PDGF. These data suggest that EGF may have an important role in maintaining the integrity of the seminal vesicle and the prostate in the mouse. While the seminal vesicle appears to acquire EGF by uptake from the environment, the prostate may have the ability to synthesize EGF locally. PMID- 1635154 TI - Evidence for a non-androgenic role of testis and epididymis in androgen-supported growth of the rat ventral prostate. AB - A widely held view is that the role of testis in prostatic growth is through its ability to secrete androgen. Our earlier observation suggested a non-androgenic role for the testis, and perhaps the epididymis, in promoting growth of the ventral prostate in rats. The present study was conducted to evaluate the separate role of the testis and the epididymis in this phenomenon. In the first study, increasing quantities of silastic tubing filled with crystalline testosterone were implanted into adult Sprague-Dawley rats at the time of bilateral epididymo-orchiectomy or sham-operation. Twenty-eight days later, growth of the ventral prostate, as determined by fresh weight, DNA, and protein content, was significantly greater in sham-operated rats than in those receiving combined epididymo-orchiectomy, confirming our previous observation using dihydrotestosterone. In the second and third studies, rats were subjected to selective surgical procedures to evaluate the independent role of the testis and the epididymis. At the same time, 12 cm silastic tubing filled with testosterone or dihydrotestosterone were implanted subcutaneously into each of these animals for 28 days. Results indicated that the ventral prostate was significantly smaller in rats receiving the combined epididymo-orchiectomy than that of sham operated controls. Simple orchiectomy or simple epididymectomy resulted in an increased weight of the ventral prostate between the two values obtained from the above two groups. Ligation of either the efferent duct or the vas deferens yielded ventral prostatic weights comparable to the androgen-treated, sham operated controls. These results indicated that in order to achieve a maximal effect on androgen-supported growth of the ventral prostate, the presence of both the testis and the epididymis is required. PMID- 1635155 TI - Effect of intracavernous simultaneous injection of acetylcholine and vasoactive intestinal polypeptide on canine penile erection. AB - We investigated the effects of intracavernous injection of a combination of acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) on the erectile response in eleven adult male dogs. The minimum dose of ACh which increased the intracavernous pressure in eight dogs varied from 0.2 to 40 micrograms, and the minimum dose of VIP varied from 0.2 to 5 micrograms. When the minimum doses of ACh and VIP were injected simultaneously, a strong increase of intracavernous pressure (the mean increase was 102 cm. H2O from the baseline level) and a sustained erection (mean 5 min.) were observed in all eight dogs. The effect of simultaneous injection of both drugs was not additive but synergistic. Pretreatment with VIP-antibody and atropine intracavernously suppressed the erectile response induced by cavernous nerve stimulation. VIP may increase the affinity of muscarinic receptors for ACh in canine corpus cavernosum because pretreatment with atropine alone before the simultaneous injection of ACh and VIP completely abolished the effect of the combination. We conclude that ACh and VIP may play a cooperative role in canine penile erection. PMID- 1635156 TI - Mechanism of ammonium transport by intestinal segments following urinary diversion: evidence for ionized NH4+ transport via K(+)-pathways. AB - Using a previously reported in vivo intestinal perfusion model in the rat, we have shown that net total ammonium absorption accounts for the majority of the acid load resulting from urinary intestinal diversion. In the present study, by varying perfusate pH and therefore NH3 concentrations, we demonstrated that the net flux of total ammonium did not correlate with non-ionized NH3 concentrations (r = .039). This indicates that the basic mechanism of total ammonium flux is via ionized NH4+ movement. To more precisely define the transport processes involved, we manipulated this system with the following chemical and pharmacologic probes of electrolyte transport: amiloride (0.5 mM/l.), furosemide (1 mM/l.), 2,4,6 triaminopyrimidine (TAP) (15 mM/l.), methylprednisolone (3 mg./100 gm./B.W.) S.Q. x 3 days followed by perfusion, and barium (Ba2+) (15 mM/l.). Net solute flux was not significantly altered by the mucosal addition of amiloride or TAP. Methylprednisolone treated rats exhibited significantly diminished Na+ secretion (p less than .01) and increased Cl- absorption (p less than .05) without affecting net total ammonium flux providing evidence for the inducibility of Na+ conductance channels and against significant NH4+ movement via this pathway. The mucosal addition of furosemide resulted in significantly decreased net absorption of both total ammonium (p less than .001) and K+ (p less than .05). The addition of Ba2+ resulted in a three-fold reduction of ammonium absorption (p less than .001) and a greater than ten-fold reduction in K+ absorption (p less than .001). The observation of significant inhibition of ammonium absorption by furosemide and barium suggests that K+ transport pathways play a significant role in the intestinal transport of NH4+. PMID- 1635157 TI - Inhibition of rat bladder tumor (RBT323) growth by tumor necrosis factor alpha and interferon-gamma in vivo. AB - The antiproliferative activities of recombinant rat gamma-interferon and recombinant human tumor necrosis factor alpha were evaluated in a new rat bladder tumor model, RBT323. The RBT323 is a spontaneously arisen, serially transplantable, bladder tumor in ACI rats. Histologically and ultrastructurally this tumor is a grade 2-3 transitional tumor without squamous cells. The RBT323 appears to be non-immunogenic in tumor excision and rechallenge experiments. The tumor was transplanted subcutaneously and the drugs were administered peritumorally. Gamma-interferon and tumor necrosis factor monotherapy starting two days after tumor implantation showed dose-dependent growth inhibiting effects in the dose range tested. Combination treatment with gamma-interferon and the highest dose of tumor necrosis factor resulted in synergistic antiproliferative effects. After cessation of the combination treatment all tumors resumed growth, initially with a low doubling time, but finally with their original growth rate. Gamma-interferon treatment initiated at a tumor volume of 0.2 to 0.5 cm.3 had no antitumor effects, whereas treatment with 100 micrograms. tumor necrosis factor per rat inhibited tumor growth significantly. Different combinations of the cytokines had synergistic effects against established tumors. These studies demonstrate antitumor effects of gamma-interferon and tumor necrosis factor in a rat bladder tumor model system. Combination therapy has synergistic effects and prolongs the time to tumor recurrence. PMID- 1635158 TI - Morphological changes and alterations in regional intrarenal blood flow induced by graded renal ischemia. AB - A model of renal ischemia was used to study morphological changes and alterations in intrarenal blood flow. Renal artery blood flow was reduced from 120 to 20 ml./minute (normal 172 +/- 14) for 3 weeks. Morphological changes were assessed histologically, and by electronmicroscopy. Intrarenal blood flow was determined using microspheres. Flow rates less than 80 ml./minute resulted in a progressive loss of renal volume with arterial thrombosis and renal infarction at 20 ml./minute. Histological changes included loss of glomerular volume, tubular dilatation (60 ml./minute), tubular cast formation (50 ml./minute) tubular atrophy, interstitial fibrosis, arteriolar thickening (40 ml./minute) and glomerular hyalinization (30 ml./minute). Electronmicroscopy changes at 60 ml./minute (loss of glomerular microvasculature, unfolding of glomerular vascular tuft, appearance of blind ending vessels) progressed to disruption of glomerular architecture noted at 30 ml./minute. Narrowing of medullary blood vessels (60 ml./minute) and neovascularisation (40 ml./minute) was observed. Progressive ischemia decreased medullary, inner cortical and outer cortical blood flow (5.9 to 2.1 ml./minute/gm.) p less than 0.01, with a compensatory increase to the opposite kidney. PMID- 1635159 TI - Collagen alterations in the corpus cavernosum of men with sexual dysfunction. AB - Previous studies have noted the abundance of collagen in human erectile tissues and the association of altered collagen content with erectile dysfunction. We investigated these notions by studying the collagen characteristics of biopsies from the corpus cavernosum of men who required surgical correction of their sexual dysfunction. Histologic analysis revealed abundant collagen within the erectile tissues. With the exception of patients with Peyronie's disease and priapism, only mild alterations in collagen architecture were noted in the remainder of the patients. Biochemical quantitation confirmed the histologic study. The mean collagen content represented 47% of total protein in most patients. The proportion rose to 68% and 73% in the patients with Peyronie's disease and priapism, respectively. No statistical difference in collagen content was noted in all the patients studied. Immunohistochemistry revealed collagen types I and IV to predominate in the corpus cavernosum, with type III making up the minority. There were no qualitative changes in collagen ratios with age and disease. We conclude that though collagen is a major component of the penis, there are no changes in its histologic characteristics that can be correlated to senescence or to the etiology of erectile dysfunction. PMID- 1635160 TI - [Analysis of the GPIIb and GPIIIa genes in patients with Glanzmann's thrombasthenia]. AB - Glanzmann's thrombasthenia (GT) is an autosomal recessive bleeding disorder due to a deficiency or abnormality of glycoproteins (GPs) IIb and IIIa, but its genetic basis remains to be determined. We analyzed the genes for GPIIb and 3'GPIIIa in 3 patients with GT and in 7 control subjects by Southern blot. No large deletions or insertions were detected in these genes in any patient with GT. Furthermore, the GPIIb and GPIIIa mRNAs derived from the platelets of patients with GT could be amplified using the reverse transcriptase-polymerase chain reaction (RT-PCR). This finding indicates that the mRNAs of the patients with GT are considered to be normally transcribed. The molecular defects of the GPIIb. PMID- 1635161 TI - [Multicenter clinical evaluation of red cell concentrates stored up to 6 weeks in MAP, a new additive solution]. AB - The clinical safety and efficacy of transfusion of red cell concentrates stored in MAP solution (MAP-CRC) containing mannitol, adenine, glucose, phosphate and citrate, into 39 anemic patients were evaluated. In 23 patients, infusion of MAP CRC was alternated with infusion of ordinary CRC as a control. The MAP-CRC and CRC used in this study were stored at 4 degrees C for an average of 38.2 +/- 2.6 days (n = 52) and 18.1 +/- 2.2 days (n = 26), respectively. Red cell recovery was 77.5% for MAP-CRC and 82.5% for CRC, based on calculation of the increase in hemoglobin level one day after transfusion. There were no differences between patients transfused with MAP-CRC and those transfused with CRC in clinical findings or biochemical data. No major side-effects other than pyrexia associated with the underlying infections were seen in patients transfused with MAP-CRC. MAP CRC stored up to 42 days is apparently as safe and effective as stored CRC. This new additive solution may therefore be useful for the future expansion of the indications for autologous blood transfusion by facilitating the collection and storage of more blood in the liquid state for a longer period, and may also be useful in obtaining more plasma from whole blood as source plasma. PMID- 1635162 TI - [Clinical evaluation of traditional Chinese medicine for chronic idiopathic thrombocytopenic purpura]. AB - The efficacy of traditional Chinese medicine (Kampo medicine) was examined in 40 patients with steroid-unresponsive idiopathic thrombocytopenic purpura (ITP). All patients were, at first, given Hochuekihi-to, and when they were refractory, therapy was switched to Sairei-to, Ninjinyoei-to, and Kamikihi-to. The efficacy rate was 20.0% by Hochuekihi-to, 20.7% by Sairei-to, 5.5% by Ninjinyoei-to and 6.7% by Kamikihi-to, respectively. Thus, overall responders were 12 in 40 patients with an effective rate of 30.0%. The mechanism of action of traditional Chinese medicine is discussed in relation to the production of various kinds of cytokines. PMID- 1635163 TI - [Abnormalities of beta spectrin with hereditary elliptocytosis in mother and child]. AB - It is generally considered that abnormality of the erythrocyte membrane skeleton co elliptocytes. There are, however, few reports of beta spectrin variants. We found a new variant of beta spectrin in a child and her mother. This report is the first case of abnormality of beta spectrin in Japan. The propositus was an 8 month-old girl who was first examined by us in 1988. On laboratory findings, she showed anemia, increased reticulocyte count and decreased haptoglobin concentration. Both peripheral blood smears of patient and her mother showed typical elliptocytosis and they were diagnosed as hereditary elliptocytosis. SDS PAGE patterns of the red cell membranes of the propositus and her mother were characterized by the presence of an abnormal component migrating immediately below the spectrin chains. We confirmed that the abnormal spectrin appeared clearly at the expense of normal beta chain. The abnormal spectrin (M.W. 216,000d) makes up 16% of the total beta chain. The inheritance of our case was autosomal dominant. The present case is considered as a new spectrin variant. PMID- 1635164 TI - [Hematopoietic failure of a healthy child with human parvovirus B19 infection- studies on the hematopoiesis]. AB - An 8 year-old boy, who had been healthy since his birth, presented fever, ecchymosis and nasal bleeding. His peripheral blood picture showed pancytopenia and bone marrow showed erythroblastopenia, but these findings recovered spontaneously in two weeks. The diagnosis of human parvovirus B19 (HPVB19) infection was made by the presence of anti HPVB19 IgM antibodies in the sera. In order to investigate the mechanisms of erythroblastopenia and pancytopenia, we performed in vitro hematopoietic cell culture in both acute phase and the convalescent phase (3 months after the onset). In the acute phase, the formation of CFU-E colony was inhibited but that of BFU-E, CFU-G, GEMM colony was not inhibited. Unexpectedly, HPVB19 DNA was detected in CFU-GEMM colony cells with the PCR technique. It is suggested that HPVB19 infected not only to erythroid progenitor cells but also to other progenitors. PMID- 1635165 TI - [Familial occurrence of myelodysplastic syndrome concomitant with monoclonal gammapathy]. AB - Myelodysplastic syndrome (MDS) combined with monoclonal gammopathy or multiple myeloma has rarely been reported. In this article, two siblings, a brother and his sister who showed simultaneous occurrence of MDS and monoclonal gammopathy are reported. The first case, a 73-year-old male, was admitted to our hospital in November, 1987. Analysis of peripheral blood revealed pancytopenia without blast cells. Bone marrow was hypocellular with 14.9% of myeloblasts and 2.8% of plasma cells characterized by 2 to 4 nuclei. Serum IgA level was 635 mg/dl and serum immunoelectrophoresis revealed a monoclonal IgA lambda band. The second case, a 70-year-old female, younger sister of the first case, was admitted to our hospital in January, 1988. Bone marrow was normocellular with 23% of peroxidase negative myeloblasts and 12.8% of atypical plasma cells. Serum IgG level was 1,901 mg/dl with monoclonal IgG kappa band. Hematological findings have remained unchanged for 12 months. The first case was regarded as hypoplastic MDS with monoclonal gammopathy and the second case was MDS with smoldering myeloma. These cases were very similar with in respect to age, time of onset, clinical course, hematological findings and especially, association with M-protein. There are no reports concerning the familial incidence of MDS with M-protein. These findings supported the hypothesis that an initial event selects a clone of stem cells which retain the capability to differentiate into mature myeloid and lymphoid cells, in these cases B-cells. PMID- 1635166 TI - [Myelodysplastic syndromes in two young brothers]. AB - Myelodysplastic syndromes that occurred in two young brothers are reported. A 19 year-old man was admitted to Kobe City General Hospital in May 1990 because of fever and nasal bleeding. On admission his hemoglobin was 5.5 g/dl, platelet count 1.5 x 10(4)/microliters and white cell count 1,700/microliters with 18% neutrophils and 80% lymphocytes. Bone marrow aspirate showed dysplastic features of trilineage blood cells with 4.8% myeloblasts. A diagnosis of refractory anemia was made. His younger brother, a 17-year-old man was examined in May 1990 because of increasing fatigability of 2 years' duration. His hemoglobin was 8.7 g/dl, platelet count 2.1 x 10(4)/microliters and white cell count 2,800/microliters. Bone marrow aspirate revealed morphological abnormalities in three lineages with 5.2% myeloblasts. He was diagnosed as having refractory anemia with excess of blasts. Their parent are consanguineous. The onset at a young age, reduced CD4 lymphocytes and similarity of dyshematopoietic findings suggests the presence of common genetic disorder in the pluripotent hematopoietic stem cells. PMID- 1635167 TI - [Myelodysplastic syndrome associated with marked eosinophilia and basophilia]. AB - Myelodysplastic syndrome (refractory anemia with excess of blasts; RAEB) with marked basophilia and eosinophilia is described. An 82-year-old male was admitted to our hospital because of severe normocytic normochromic anemia (Hb 5.6 g/dl). The white cell count was 9,200/microliters with marked basophilia (34.5%) and eosinophilia (19.5%). The bone marrow aspiration also revealed both basophilia and eosinophilia, with blast contents of 9%. Diagnosis of RAEB was established. Although the treatment with red cell transfusion and ubenimex (Bastatin) was started, anemia was not improved. A karyotype of the bone marrow cells from this patient showed 47, XY, +8, i (17q), which has been observed as additional chromosomal abnormalities in blastic crisis of chronic myelogenous leukemia. The diagnosis of CML was not compatible with this case, because Ph1 chromosome and bcr gene rearrangement were negative. It is concluded that eosinophilia and basophilia might be derived from clonal abnormalities associated with MDS. PMID- 1635168 TI - [Erythroleukemia in pregnancy with successful outcome of delivery]. AB - A 37-year-old woman was admitted to our hospital because of anemia in the 33rd week of pregnancy. On admission, the hemoglobin was 7.6 g/dl, platelets 508,000/microliters and WBC 8,300/microliters with 4% blast cells. Bone marrow aspirate demonstrated 50% erythroblasts of nucleated cells, which had prominent megaloid and polynucleic changes, and 20% myeloblast cells. We diagnosed her as having erythroleukemia. Receiving packed-red-cell transfusions, she had a cesarean section, and gave birth to a female infant (BW 2,175 g) in the 34th week of pregnancy. At the same time, she had a total hysterectomy with left adnexectomy. The postoperative course was favorable. She had a combination chemotherapy of BHAC-DMP, resulting in a partial remission. After the second induction chemotherapy with subcutaneous use of G-CSF and BHAC-DMP, complete remission was obtained, which lasted for almost 17 months. The child is growing well without any hematological disorder. PMID- 1635169 TI - [B-cell chronic lymphocytic leukemia complicated by autoimmune thrombocytopenic purpura]. AB - A 74-year-old Japanese male was admitted because of anemia. Hepatosplenomegaly, lymphoadenopathy, and purpura were not found. The laboratory data on admission revealed that the white-cell count was 9,400/microliters, the hemoglobin 11.1 g/dl, and the platelet count 17,000/microliters. Platelet-associated IgG was 794.2 ng/10(7) cells. The patient was diagnosed as having autoimmune thrombocytopenic purpura (ATP) at this time. He was treated with prednisolone, but his thrombocytopenia not improve. In addition to prednisolone, azathioprine was given to him. During the course of treatment, leukocytosis gradually appeared and the white-cell count reached more than 30,000/microliters with over 70% lymphocytes. A bone marrow aspiration revealed 70% of small lymphocytes, and surface marker analysis showed that CD19 and HLA-DR were positive on these lymphocytes. Southern blotting analysis demonstrated rearrangements of JH and JK. He was finally diagnosed as B-CLL complicated by ATP. One month after the azathioprine administration, the platelet count increased more than 30,000/microliters and the white-cell count decreased less than 10,000/microliters. About 2% of patients with CLL are known to be complicated by ATP. To our knowledge, the present case is the first case of B-CLL complicated by ATP in Japan. PMID- 1635170 TI - [Lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2) therapy that improved lymphadenopathy in a patient with B cell non-Hodgkin's lymphoma]. AB - A 70-year-old man was admitted to our hospital on March 9, 1989 because of fever, superficial generalized lymphadenopathy, upper abdominal mass and right pleural effusion. The diagnosis of non-Hodgkin's lymphoma (follicular medium sized cell type, B cell) was made by a biopsy of the neck lymph node. Peripheral blood mononuclear cells were obtained from the patient by cytopheresis. The cells were cultured for 8 days with interleukin-2 (IL-2) to generate Lymphokine-activated killer (LAK) cells. The patient received a total of 7.7 x 10(9) LAK cells intravenously over a period of 3 weeks. He also received continuous intravenous infusion of IL-2 for 17 days, starting 2 days before the first infusion of LAK cells. After this therapy, although his superficial generalized lymphadenopathy disappeared or decreased in size, the size of the upper abdominal mass did not decrease. Therefore, it is suggested that adoptive immunotherapy is a beneficial treatments for B cell lymphoma. However, LAK cells should be generated in much larger quantities for a more successful therapeutic result. PMID- 1635171 TI - [Hodgkin's disease associated with Behcet's disease]. AB - This paper reports a rare case of Hodgkin's disease with Sjogren syndrome in the course of Behcet's disease. A 43-year-old man developed arthralgia of bilateral knees, ankles, elbows and wrists in May, 1988. He had hazy vision and was diagnosed as having iridocyclitis and chorioretinitis in February, 1989. Gingival ulcer, penile ulcer, erythema nodosum on the right lower leg and superficial thrombophlebitis on the bilateral arms appeared in June, 1989. Therefore, he was diagnosed as Behcet's disease. He responded well to prednisolone. In November, 1989, he developed fever with positive CRP and elevated alkaline phosphatase. Multiple mass lesions in the liver and spleen with retrocrural lymphadenopathy were noticed on the abdominal CT and echogram. A cervical lymph node biopsy revealed Hodgkin's disease of the mixed cellularity type. At the same time, the patient had dry eyes and a dry mouth. Salivary gland biopsy revealed chronic sialoadenitis with lymphocytic infiltration compatible with Sjogren syndrome. The patient responded well to ABVD regimen. He is still free of disease as of May, 1991. PMID- 1635172 TI - [Hairy cell leukemia successfully treated with 2'-deoxycoformycin following refractoriness to splenectomy and alpha-interferon therapy]. AB - A 34-year-old man was admitted in May, 1989 because of severe left upper abdominal pain, which was caused by advanced splenomegaly. On initial examinations, peripheral blood showed leukocytosis (13,400/ml) including 60% hairy cell which also infiltrated in bone marrow (64%). The patient was diagnosed as having hairy cell leukemia (Japanese type) of B-cell lineage. Splenectomy was performed as an initial treatment. The effect of splenectomy was only palliative and transient leukocytosis progressed thereafter. alpha-interferon and bestrabucil (KM 2210) were then adopted for 4 months respectively. The effects were, however, unsatisfactory. Subsequently the patient was treated successfully with 2'-deoxycoformycin (DCF). Complete remission was attained following 12 injections of 7.5 mg/body of DCF during 5 months and durable remission persists for more than 6 months without maintenance therapy. The side effect was minimum. PMID- 1635173 TI - [Idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia with elevated level of serum interleukin-6]. AB - A 38-year-old male was admitted in January 1984 due to lymphadenopathies with hyperimmunoglobulinemia with a serum IgG level of 2,872 mg/dl. Following this, he was observed as an outpatient in regard to lymphadenopathies of unknown origin. In 1989, after the fourth lymph node biopsy he was diagnosed as having idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia. At that time his serum IgG level was 8,090 mg/dl. The elevated serum interleukin-6 (IL-6) level, up to 21.1 pg/ml, was particularly interesting, because IL-6 is involved in the oncogenesis of plasmacytoma/myeloma. The patient also had thrombocytosis, hematuria, and a serum increased level of C reactive protein which seemed to be related to the effects of IL-6 i.e. thrombopoiesis, induction of the proliferation of mesenchymal cells, and induction of the production of acute phase proteins by hepatocytes, respectively. Even though he displayed no outward symptoms before and after treatment with prednisolone and melphalan, elevated immunoglobulin levels were still present. PMID- 1635174 TI - [Natural interferon-alpha induced cytogenetic complete remission in a patient with chronic myelocytic leukemia, diagnosed in early chronic phase with basophilia and normal blood cell counts]. AB - A 57-year-old woman visited to our hospital complaining of paresthesia in the right leg. She had no abnormal physical findings. However, the peripheral blood examination demonstrated 7% basophilia with 8000/microliters WBC count and decreased neutrophil alkaline phosphatase activity (score 37, rate 19%). She was diagnosed as Ph1 chromosome positive CML in early phase by the chromosomal analysis of bone marrow cells. She received subcutaneous injection of natural interferon-alpha at a dosage of 600 x 10(4) IU daily from March 10, 1987. The dosage and administration interval were gradually reduced and prolonged. Since November 1988, weekly injections of 300 x 10(4) IU has been administered as maintenance therapy. Cytogenetic improvement was seen at 4 months after the start of IFN. Disappearance of Ph1 chromosome positive cells was observed on December 11, 1987. It was suggested that the administration of IFN from the early chronic phase played an important role in the control of the disease. PMID- 1635175 TI - [alpha-Interferon in the treatment of essential thrombocythemia]. AB - Two patients with essential thrombocythemia were successfully treated by administering native alpha-interferon (alpha-IFN). One patient was a 38-year-old man in whom thrombocytosis was found accidentally. His platelet count on admission was 880,000/microliters and megakaryocytes increased. Three million units of alpha-IFN was administered subcutaneously everyday, and the platelet count decreased gradually to about 500,000/microliters within 2 weeks. The other patient was a 66-year-old woman who visited our hospital complaining of tenderness and swelling of the fingertips. Her platelet count was 1,610,000/microliters, and megakaryocytes increased and showed abnormal morphology. Six million units of alpha-IFN was administered subcutaneously every other day. The tenderness and swelling of the fingertips disappeared soon after the beginning of alpha-IFN administration. The platelet count decreased to about 500,000/microliters within 10 days, but she developed itching of the skin over the entire body. Therefore, alpha-IFN treatment was discontinued. It was suggested that alpha-IFN suppresses not only the maturation and proliferation of the progenitors of megakaryocytes but also the production of platelets from megakaryocytes. Administration of alpha-IFN should be considered in treating patients with essential thrombocythemia, because effects appear soon and alpha IFN does not induce a second malignancy. PMID- 1635176 TI - [Alveolar rhabdomyosarcoma with massive bone marrow involvement and 2;13 chromosome translocation]. AB - We report a 9-year-old girl who had massive bone marrow infiltration of tumor cells at the onset of alveolar rhabdomyosarcoma. She was admitted to a surgical hospital because of abdominal pain and tumor in the buttock. Computerized tomographic scans of the pelvis revealed an abnormal mass. She was referred to our department. Hematological examination showed pancytopenia. Blood chemistry revealed hypercalcemia and hyperuricemia. Bone marrow was occupied with 100% tumor cells. Chromosome analysis of tumor cells in bone marrow revealed a specific translocation, t(2;13) (q37;q14). This finding enabled the diagnosis of a disseminated alveolar rhabdomyosarcoma to be established. She was treated with vincristine, cyclophosphamide and epirubicin, achieved a complete remission, but died of relapse 3 months after diagnosis. PMID- 1635177 TI - [All-trans retinoic acid induced a complete remission in a case of refractory relapsed acute promyelocytic leukemia]. AB - Forty five year old male suffering from relapsed acute promyelocytic leukemia (APL) was treated with all-trans retinoic acid (ATRA) and attained second complete remission (CR) without bone marrow hypoplasia. He was diagnosed as having APL in September 1989. The DCMP-85 regimen first induced CR in October, however the disease relapsed in September 1990. The DCMP-85 and and the MEC (MIT, ETOP, Ara-C) regimens were applied for re-induction without success. Then, 45 mg/m2/day ATRA was given orally from December 28, 1990. Laboratory data before ATRA treatment were as follows; 35.4% leukemic cells in the bone marrow, Hb 11.0 g/dl, Plt 130,000/microliters, WBC 5,100/microliters without leukemic cells, and no DIC was detected. During the treatment, his bone marrow was examined frequently. The bone marrow series showed no hypoplasia at any time and gradual reduction of leukemic cells with proliferation of mature granulocytes. CR was attained on January 21, 1991. DIC did not develop. Cytogenetic anomalies including t(14;17;15) (q24;q11.2;q22) reduced from 29/30 cells at relapse to 4/30 cells at the time of CR. Dryness of mouth and lips, irritation around eyes and the elevations of GOT, GPT and triglyceride level were seen as the side effects of ATRA, however they were tolerable. PMID- 1635178 TI - [Differentiation therapy of acute promyelocytic leukemia: two successful cases of remission induction by all-trans retinoic acid]. AB - We described two pediatric patients with acute promyelocytic leukemia (APL) who were successfully induced into complete remission with all-trans retinoic acid (ATRA, 45 mg/m2 per day) after failing on conventional chemotherapy. Initial response was observed as correction of DIC within a week of treatment. Hematologically, initial increase of maturing leukocytes reached a peak peripheral WBC count on the 16th and 20th day, respectively. However, these seemingly differentiated leukocytes retained Auer body and dysplastic features and there was no concomitant recovery of erythroid and megakaryocytic lineages at this point. A sudden drop of leukocyte counts after this peak made a brief period of leukopenia before the complete remission was finally attained morphologically in 4-5 weeks. Thus, remission of APL by ATRA therapy consisted of a two-phase course. In one patient, we observed an increase of histiocytes phagocytizing leukocytes in the marrow during the recovery from leukopenia. It is, therefore, postulated that the two-phase course of recovery may reflect the differentiation of leukemic cells by ATRA and subsequent clearance of senescent cells by the reticuloendothelial system followed by regeneration and differentiation of residual normal hematopoietic stem cells. PMID- 1635179 TI - [Improvement of bone marrow hematopoiesis in idiopathic myelofibrosis with prednisolone]. AB - A 64 year-old female patient of idiopathic myelofibrosis (IMF), who had had rapidly progressing massive splenomegaly and severe pancytopenia refractory to blood transfusion, was treated with PSL 0.6 mg/kg/day for a month, being significantly improved not only symptomatically and hematologically but also in bone marrow hematopoiesis. Although the effectiveness of PSL to restoration of bone marrow hematopoiesis has been almost unknown, long term oral PSL should be tried for a certain phase of IMF. PMID- 1635180 TI - [Pharmacology and action mechanism of calcium and magnesium as regulators of blood pressure]. PMID- 1635181 TI - [Pharmacology and action mechanism of endothelium-derived relaxing factor]. PMID- 1635182 TI - [Neural network of circulatory control system]. PMID- 1635183 TI - [Roles of cytokines on blood pressure regulation]. PMID- 1635184 TI - [Insulin--pharmacological aspects]. PMID- 1635185 TI - [Definition of high blood pressure]. PMID- 1635186 TI - [Comparison of various methods of measuring blood pressure]. PMID- 1635187 TI - [A clinical significance and limitation of home blood pressure measurements]. PMID- 1635188 TI - [Ambulatory blood pressure monitoring in hypertensive patients]. PMID- 1635189 TI - [Classification and severity of hypertension]. PMID- 1635190 TI - [Hypertension detection and follow-up program(HDFP)]. PMID- 1635191 TI - [An epidemiology of hypertension in Japanese]. PMID- 1635192 TI - [The changing pattern of hypertension and incidence of cardiovascular diseases in a long-term follow-up survey of a Japanese community: the Hisayama Study]. PMID- 1635193 TI - [Long-term trends in blood pressure observed in rural and urban populations]. PMID- 1635194 TI - [Long-term follow-up of hypertension in work site population]. PMID- 1635196 TI - [Genetic background of hypertension]. PMID- 1635195 TI - [An epidemiological analysis of cardiovascular diseases in the subtropical islands of Okinawa]. PMID- 1635197 TI - [The background of racial difference in hypertension]. PMID- 1635198 TI - [Simulation of cardiovascular control system]. PMID- 1635199 TI - [Characteristics in prehypertensive stage of essential hypertension]. PMID- 1635200 TI - [Pathogenesis of essential hypertension--a perspective]. PMID- 1635201 TI - [Autonomic nervous system in essential hypertension]. PMID- 1635202 TI - [Role of sodium and potassium in the pathogenesis of essential hypertension]. PMID- 1635203 TI - [Arterial factors in essential hypertension]. PMID- 1635204 TI - [Etiological and physiopathological significance of catecholamine activity in hypertension]. PMID- 1635205 TI - [Etiological and physiopathological significance of serotonin activity in essential hypertension]. PMID- 1635206 TI - [Etiological significance of the renin-angiotensin system in essential hypertension]. PMID- 1635207 TI - [Etiological and physiopathological significance of vasopressin activity in essential hypertension]. PMID- 1635208 TI - [Etiological significance of prostaglandins and related substances in hypertension]. PMID- 1635209 TI - [Diurnal variation of blood pressure]. PMID- 1635210 TI - [The kallikrein-kinin system and blood pressure regulation in essential hypertension]. PMID- 1635211 TI - [Etiological significance of calcium and magnesium activity in essential hypertension]. PMID- 1635212 TI - [Etiological significance of calcium regulating hormones in hypertension]. PMID- 1635213 TI - [Etiological and physiopathological significance of endothelin activity in essential hypertension]. PMID- 1635214 TI - [Etiological and physiopathological significance of cytokine activity in hypertension]. PMID- 1635215 TI - [Etiological and physiopathological significance of growth factor activity in hypertension]. PMID- 1635216 TI - [Insulin--its role in the pathogenesis of hypertension]. PMID- 1635217 TI - [Etiological and physiopathological significance of steroid hormones in hypertension]. PMID- 1635218 TI - [Etiological and physiopathological significance of taurine in hypertension]. PMID- 1635219 TI - [Miscellaneous factors on mechanisms of blood pressure regulation]. PMID- 1635220 TI - [Molecular biology in renin angiotensin system]. PMID- 1635221 TI - [Essential hypertension and cerebral blood flow]. PMID- 1635222 TI - [Renal hemodynamics in essential hypertension]. PMID- 1635223 TI - [Peripheral vascular hemodynamics in essential hypertension]. PMID- 1635224 TI - [Disorders of renal sodium excretion in essential hypertension]. PMID- 1635225 TI - [Electrolyte transport in the blood cell membrane and essential hypertension]. PMID- 1635226 TI - [Changes in platelet function in essential hypertension]. PMID- 1635227 TI - [Hypertension and microvascular rheology]. PMID- 1635228 TI - [Diurnal rhythm of blood pressure in normotensive subjects and patients with essential hypertension]. PMID- 1635230 TI - [Circadian changes in blood pressure before and after admission]. PMID- 1635229 TI - [Mechanisms and sources of circadian variations in blood pressure]. PMID- 1635231 TI - [A clinical significance of nocturnal blood pressure]. PMID- 1635232 TI - [Sodium, potassium and calcium intake and hypertension]. PMID- 1635233 TI - [Alcohol and hypertension]. PMID- 1635235 TI - [Effects of alcohol on circadian blood pressure pattern]. PMID- 1635234 TI - [Possible mechanisms of alcohol-induced hypertension]. PMID- 1635236 TI - [Smoking as a factor altering blood pressure: acute and chronic effects]. PMID- 1635237 TI - [Cold stimulation and essential hypertension]. PMID- 1635238 TI - [Psychological stress and blood pressure]. PMID- 1635239 TI - [Exercise and essential hypertension]. PMID- 1635240 TI - [Blood pressure during sleep]. PMID- 1635241 TI - [Biosynthetic pathway of endothelin]. PMID- 1635242 TI - [Seasonal differences in blood pressure]. PMID- 1635243 TI - [Disturbance of cerebral circulation in hypertension--introduction]. PMID- 1635244 TI - [Pathogenic mechanisms of hypertensive cerebrovascular lesions--importance of regional nutrition]. PMID- 1635245 TI - [Echocardiographic findings in hypertensive heart disease--evaluation of cardiac structure and function]. PMID- 1635246 TI - [The relationship between hypertension and hypertrophic cardiomyopathy]. PMID- 1635247 TI - [Renal disorder (nephrosclerosis) in hypertension]. PMID- 1635248 TI - [Arteriosclerosis associated with hypertension]. PMID- 1635249 TI - [Ocular fundus changes in essential hypertension]. PMID- 1635250 TI - [Sleep apnea syndrome and hypertension]. PMID- 1635251 TI - [Pressure-regulating factors--pharmacology and action mechanisms. Catecholamines]. PMID- 1635252 TI - [Hypertension and sudden death]. PMID- 1635253 TI - [Classification of antihypertensive agents]. PMID- 1635254 TI - [Thiazides and thiazide-like diuretics]. PMID- 1635255 TI - [Loop diuretics]. PMID- 1635256 TI - [Potassium-sparing diuretics]. PMID- 1635257 TI - [Centrally acting sympathetic inhibitors]. PMID- 1635258 TI - [Presynaptic adrenergic neuron blocking drugs]. PMID- 1635259 TI - [Regional flows in conscious hypertensive rats]. PMID- 1635261 TI - [Relaxants of arterial and arterio-venous smooth muscles]. PMID- 1635260 TI - [Blood pressure regulating factors--pharmacology and action mechanisms. Serotonin]. PMID- 1635262 TI - [Ca antagonists]. PMID- 1635263 TI - [Nonpeptide angiotensin II antagonists]. PMID- 1635264 TI - [Renin inhibitors]. PMID- 1635265 TI - [Renin angiotensin system as a regulator of blood pressure--pharmacological actions and its mechanisms]. PMID- 1635266 TI - [Serotonergic antagonist]. PMID- 1635267 TI - [Pharmacology and action mechanism of vasopressin as a regulator factor of blood pressure]. PMID- 1635268 TI - [Pharmacology and action mechanism of prostaglandins and related substances as regulators of blood pressure]. PMID- 1635269 TI - [Pharmacology and action mechanism of kallikrein-kinin system as a regulator of blood pressure]. PMID- 1635270 TI - [Development of a scale for workers' coping behavior: its reliability and validity]. AB - The purpose of this study is to develop a scale for measuring coping with job stressors. Stress process and coping function provide the theoretical framework. Coping is conceptualized as situation-specific behavior. We measure episodic coping, that is, the strategies that individuals actually use in coping with a particular situation. First, a preliminary scale, was prepared. It contained 39 coping behaviors with job stressor which were based on an open-ended pilot study. Next, factor analysis was conducted in order to identify the structure of the scale. Subjects of this study were 649 male employees and 91 female employees of a in manufacturing firm and research and development institute. By occupation they were comprised of 383 professionals, 99 technicians, 96 clerks, 104 miscellaneous workers and 58 of unknown occupation. Seven items in the preliminary scale were omitted because of their psychometrical properties. Finally, factor analysis showed three factors in the scale: positive action and cognition (11 items), avoidant action and cognition (10 items), and symptom management (11 items). The coping scale showed high conceptual validity and reliability. PMID- 1635271 TI - [Person-centered approach in occupational mental health: theory, research and practice]. AB - The objective of this study was to articulate the person-centered approach (PCAp) in theory and in the research and practice of occupational mental health. First, Carl Rogers' person-centered theory was reviewed. Secondly, a study on 1,661 workers was presented in which psychological variables such as fatigue (FG), depression (DP) and anxiety (AX) were found to be negatively correlated with relationship scales concerning the workers' perception of the person-centered attitudes (PCA) of their superiors, the democratic leadership of their superiors (DEM) and the overall activation (ACT) of their worksites. Significant differences in FG, DP and AX were found among workers who perceived of their superiors as having either high or low PCA. Workers who reported that their superiors had high PCA had significantly less FG, DP and AX than those who perceived of their superiors as having low PCA. Similar results were also obtained when high DEM/low DEM and high ACT/low ACT were compared in terms of workers' FG, DP and AX. Thus, the PCA of job superiors was considered to be positively related to the mental health of workers. Thirdly, PCA training in industry was introduced and evaluated. A total of 137 trainees (managers) conducted active listening, a basic skill in the PCAp, and filled out a relationship inventory immediately afterwards, evaluating themselves as listeners and their partners as listeners. A comparison of scores between the first and last sessions of training showed significant increases in empathy, congruence and unconditional positive regard at the last session in both the speakers' version and the listeners' version of the relationship inventory. Cases showing changes in human relations at work as a consequence of PCA training, reported by the trainees and confirmed by an occupational health nurse, were presented. This study showed that PCA, which is positively related to workers' mental health, can increase as a result of training. The implications of these studies are discussed and various possibilities for further research using the concepts of PCAp are presented. The authors hope that such a viewpoint in occupational mental health may lead to fruitful research and practice in the field of occupational medicine. PMID- 1635272 TI - [Excretion of p-chloroaniline metabolites into urine. Excretion of 2,4 dichloroaniline and p-chloroformanilide]. AB - Previously, we identified by gas chromatography/mass spectrometry (GC/MS) urinary metabolites of p-chloroaniline (p-CA) in a patient with acute p-CA poisoning. Among these metabolites there is a possibility that 2,4-dichloroaniline (2,4-DCA) and p-chloroformanilide (p-CFA) are produced through some unknown metabolic pathways in human. In order to clarify whether 2,4-DCA and p-CFA were produced within the human body or not, an attempt was made to detect these metabolites in the patient's urine samples prepared by various pretreatments, using both GC/MS and high performance liquid chromatograph. In addition, the detection of these metabolites in non-exposed person's urine samples spiked with p-CA and 2-amino-5 chlorophenol was attempted by GC/MS using same the procedures in order to examine whether p-CA and 2-amino-5-chlorophenol excreted as metabolites were further changed to 2,4-DCA or p-CFA in the urine or not. 2,4-DCA was found abundantly in the ethereal extracts from the patient's urine samples hydrolyzed with hydrochloric, sulfuric and nitric acids, but only small amounts from intact urine samples by GC/MS. No 2,4-DCA was detected in the urine samples to which were added p-CA and 2-amino-5-chlorophenol. p-CFA was found in the ethereal samples which were extracted at acidic conditions from the patient's urine samples by GC/MS at the injection port temperature of 250 degrees C of the gas chromatograph, but the p-CFA peak disappeared at the injection port temperature of 150 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635273 TI - [Assessment of occupational exposures to industrial hazardous substances. V. A proposed method for evaluating employee's exposure averages (8-h TWAs) using a single day measurement]. AB - Daily exposure averages (8-h TWAs) to hazardous substances may vary considerably day to day, even though a worker is engaged in the same job. Previously we proposed a method to evaluate a long-term exposure condition with interday fluctuation using some exposure measurements. As it is assumed that 8-h TWAs are log-normally distributed, geometric standard deviation (sigma g) representing true interday fluctuation of 8-h TWAs should be estimated. If a single day's 8-h TWA of a worker is measured, sigma g of his own distribution of 8-h TWAs cannot be estimated. Therefore, to evaluate a long-term condition using a single day's 8 h TWA, representative sigma g in all industrial workplaces must be determined beforehand. To investigate sigma g observed in many industrial workplaces, two days' 8-h TWAs of each worker were measured in a week on 260 workers exposed to 19 hazardous substances. Sg2 (geometric standard deviation estimated by two samples) ranged from 1.00 to 8.22 with a median of 1.47 and a 90% upper limit of 2.47. Transforming Sg2 into sigma g, median and 90% upper limit of sigma g were 1.75 and 2.47, respectively. According to a classification scheme in the proposed method, exposure levels (I to III) were calculated using sigma g of 1.75 and 2.47. A long-term exposure condition to hazardous substances can be evaluated by comparing a single day's 8-h TWA with the exposure levels. PMID- 1635274 TI - [Questionnaire survey for the fitness of protective equipment used by workers]. PMID- 1635275 TI - [A method for storage of urine samples in the biological monitoring of organic solvents]. PMID- 1635276 TI - [Carpal tunnel syndrome in three public school lunch cooks]. PMID- 1635277 TI - Renal basolateral membrane SO4/HCO3 transporter characterized by fluorescent acridine orange. AB - Acridine orange (AO), a pH-sensitive fluorescent indicator, was used to study the characteristics of SO4/HCO3 transport in basolateral membrane vesicles (BLMV) isolated from rabbit renal cortex. The BLMV preparation containing a low buffer concentration and preloaded with 25 mM HCO3 was mixed with buffer containing AO and SO4 in the absence of an initial pH gradient. SO4 influx tended to drive HCO3 efflux, causing intravesicular accumulation of AO and fluorescence quenching. There was no AO quenching in the absence of HCO3 with or without an external SO4 gradient. 100 microM 4,4'-dibenzamido-2,2'-disulfonic stilbene (DBDS) inhibited the fluorescence quenching completely. 25 and 100 mM external Cl did not cause AO quenching. There was no effect of pH (6.5-8.0) on SO4/HCO3 transport. The Kd for SO4 was 8.2 mM. A positive inwardly directed diffusion potential (K(in) = 5 mM, K(out) = 100 mM with valinomycin) did not exert any effect on the SO4/HCO3 transport, indicating that the transport process is insensitive to voltage. The Ki for DBDS inhibition of SO4/HCO3 transport was 2.3 microM. PMID- 1635279 TI - Characterization of G-proteins in rat glomeruli. AB - G-proteins in rat glomeruli were examined using bacterial toxin-catalyzed ADP ribosylation and specific immunoblots. ADP-ribosylation catalyzed by cholera and pertussis toxin demonstrated the existence of Gs and Gi proteins in the glomerular membranes. Immunoblots further revealed two types of Gs alpha (45 and 52 kDa), Gi alpha 1 and/or Gi alpha 2 (40-41 kDa), Gi alpha 3 (40 kDa) and G beta (35-36 kDa) but not Go alpha in the membranes of the glomeruli. The predominant subspecies of Gs alpha was a 52 kDa protein. However, detectable amounts of G proteins did not exist in cytosolic extracts of the glomeruli. We conclude that several subspecies of Gs and Gi proteins are present in rat glomerular membranes. PMID- 1635278 TI - Arginine vasopressin increases intracellular calcium ion concentration in isolated mouse collecting tubule cells: distinct mechanism of action through V2 receptor, but independent of adenylate cyclase activation. AB - The effects of arginine vasopressin (AVP*2) and its V2 receptor agonist, 1 deamino-8-D-AVP (dDAVP), on the intracellular calcium ion concentration ([Ca2+]i) in isolated collecting tubular cells of mouse kidney were examined using fluorescent indicator fura-2 and a superfusion system. Both AVP and dDAVP evoked a rapid, transient increase followed by a sustained elevation of [Ca2+]i in CCT, OMCT, and IMCT in a dose-dependent manner. In CCT, the increments in [Ca2+]i by dDAVP were lower than those induced by AVP at all concentrations (10(-10)-10(-6) M) of the agonists tested, while in OMCT and IMCT, the increments were comparable. The initial peak of the rise in [Ca2+]i induced by AVP and dDAVP in these collecting tubule segments was partially attenuated by about 40% and the second sustained elevation was largely abolished in the absence of Ca2+ in the superfusate. Further, the increments [Ca2+]i induced by AVP were not affected by the addition of nicardipine to the superfusate. The increases in [Ca2+]i evoked by AVP and dDAVP were not mimicked by cAMP or forskolin. Moreover, they were not affected by alpha-adrenergic stimulation with epinephrine, in the presence and absence of prazosin, conditions which inhibit AVP-dependent cAMP production. These results indicate that AVP increases [Ca2+]i in CCT, OMCT, and IMCT, probably through V2 receptors, but via a mechanism which is independent of adenylate cyclase activation. In addition, the rise in [Ca2+]i is due to both Ca2+ release from the intracellular stores and increased Ca2+ influx through Ca2+ channels insensitive to nicardipine. PMID- 1635280 TI - Specificity of IgA antibodies in sera from patients with IgA nephropathy. AB - A study was undertaken on the specificity of circulating IgA antibodies in patients with IgA nephropathy detected by immunofluorescence using avidin-biotin complexes. Renal biopsy specimens and serum samples were obtained from 33 patients with IgA nephropathy, 14 other glomerular diseases and 3 normal renal tissues. These renal specimens were treated with citrate buffer (pH 3.2), and then incubated with serum samples obtained from the same and other patients with IgA nephropathy, other glomerular diseases or healthy adults at 37 degrees C for 30 min. The specimens were incubated with biotin conjugated gout F(ab')2 anti human IgA antiserum at 37 degrees C for 30 min, and then with fluorescein-labeled avidin at 37 degrees C for 30 min. It was found that IgA antibodies in the sera from patients with IgA nephropathy specifically combined with the autologous glomerular mesangial areas, but only 25.7% of them combined with allogeneic renal tissues of IgA nephropathy patients. Confirmatory findings were obtained using an automatic image analyzer. However, these IgA antibodies did not combine with the renal tissues from patients with other glomerular diseases or normal renal tissues. In parallel studies, in order to distinguish IgA nephropathy from other glomerular diseases before renal biopsy, the renal specimens from patients with IgA nephropathy were also incubated with serum samples obtained from 42 patients with proteinuria and/or hematuria before renal biopsy. It was demonstrated that the incidence of IgA binding in IgA nephropathy was significantly higher than that in other glomerular diseases prior to renal biopsy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635281 TI - Study on anti-IgA antibody in patients with IgA nephropathy. AB - Serum IgG antibodies to polyclonal IgA, IgA1 and IgA2 were evaluated by enzyme linked immunosorbent assay in 50 patients with IgA nephropathy and 30 healthy controls to elucidate the relationship between IgA and IgG in IgA nephropathy. Anti-IgA antibody was considered positive if the titer exceeded the mean value in normal controls by greater than 2 SD. In patients with IgA nephropathy, 18 cases (36%) demonstrated anti-IgA antibody, 19 cases (38%) anti-IgA1 antibody and 7 cases (14%) anti-IgA2 antibody. Western blots confirmed the existence of anti-IgA antibody in these patients. There were no significant differences in serum IgA concentration, serum creatinine concentration, degree of hematuria, amount of urinary protein, and rate of glomerular IgG deposition between the "positive" group and "negative" group. Although the mechanism of production and the role of this antibody remain unknown, it may represent one of the diverse immune abnormalities of IgA nephropathy and may be involved in the pathogenesis of IgA nephropathy. PMID- 1635282 TI - Clinical significance of anti-neutrophil cytoplasmic antibodies (ANCA) in collagen diseases associated with vasculitic syndrome in Japan. AB - The present study was undertaken to determine the anti-neutrophil cytoplasmic antibody (ANCA) levels in 96 patients with various collagen diseases associated with renal vasculitis and vasculitic syndrome in Japan. The results indicated that cytoplasmic(C)-ANCA is an autoantibody highly specific to Wegener's granulomatosis (WG) and that it is also active in renal injury. The relationships between ANCA and focal segmental necrotizing GN, i.e., renal vasculitis as proposed by Balow, were investigated. Perinuclear(P)-ANCA was detected with high sensitivity and specificity in renal vasculitis without WG, and the severity of necrotizing and crescentic nephritis in WG was correlated especially well with the C-ANCA titer. Detection of ANCA is considered clinically useful for the etiological differentiation of renal vasculitis, suggesting the possibility that C-ANCA may be involved in the onset of vasculitis of the glomerular capillary vessels in WG. The presence of C-ANCA and cytokines (IL-1 beta and TNF-alpha) is important in the pathogenesis of vasculitis and GN in WG. PMID- 1635283 TI - High resolution three-dimensional meshwork structure of the glomerular basement membrane. AB - To investigate the ultrastructure of the glomerular basement membrane (GBM), rat GBM was treated with sodium dodecyl sulfate and 2-mercaptoethanol and observed under an electron microscope employing ultrathin sectioning and rotary shadowing methods. Further, thick sections of the treated GBM were examined by high voltage transmission electron microscopy. A fine three-dimensional meshwork structure was clearly observed through the entire thickness of the GBM treated with sodium dodecyl sulfate and 2-mercaptoethanol by conventional transmission electron microscopy and high voltage transmission electron microscopy. The diameter of the fibrils forming the meshwork structure was about 3 nm and the dimensions of the pores present in the meshwork were 3 to 4 nm. The rotary shadowing technique revealed fine fibrils disentangled from the GBM that were bound together, and corresponded morphologically type IV collagen molecules. The present findings suggested that the GBM has a fine three-dimensional meshwork structure through its entire thickness which is composed mainly of type IV collagen and may function as a size barrier in the renal glomerulus. PMID- 1635284 TI - Effects of pravastatin on serum lipids and apolipoproteins in hyperlipidemia of the nephrotic syndrome. AB - The nephrotic syndrome is often accompanied by hyperlipidemia associated with an increased risk of accelerated atherosclerosis. The present study was undertaken to evaluate the effects of pravastatin, a novel competitive inhibitor of 3 hydroxy-3-methylglutaryl coenzyme A reductase, on the serum lipids and apolipoproteins in patients with this syndrome and marked hyperlipidemia. Eleven adult patients received 10 mg of pravastatin twice daily for 4 to 8 weeks. The total serum cholesterol decreased from 426 +/- 44 to 309 +/- 18 mg/dl (-27.4%, mean +/- S.E.; p less than 0.01) following administration of pravastatin. The serum triglyceride decreased from 332 +/- 122 to 229 +/- 50 mg/dl (-30.9%), although this change was not significant. Despite the fact that the HDL cholesterol level was barely changed (51 +/- 7 to 51 +/- 6 mg/dl), the LDL cholesterol fell from 313 +/- 30 to 211 +/- 16 mg/dl (-32.5%; p less than 0.005), and the LDL to HDL cholesterol ratio fell from 7.57 +/- 1.59 to 4.94 +/- 0.88 ( 34.8%; p less than 0.05). These changes caused the atherogenic index to decline from 9.6 +/- 2.4 to 6.1 +/- 1.2 (-36.5%; p less than 0.05). No significant alterations could be found among apolipoproteins A-1, A-2, B, C-2, C-3, and E. During the present study period, pravastatin was well tolerated and did not affect the serum protein, albumin, serum urea nitrogen, creatinine levels, or urine protein excretion. Also, there were no serious adverse effects. Pravastatin appears to be effective for treating patients with hyperlipidemia of the nephrotic syndrome. PMID- 1635286 TI - Anti-proteinuric and anti-coagulatory effects of camostat mesilate in azotemic diabetics. AB - The present study was conducted on 8 patients with advanced diabetic nephropathy who showed a significant reduction of proteinuria through ACE inhibition. Camostat mesilate, one of the most potent protease inhibitors developed for oral use, was administered to these patients at a daily dose of 600 mg starting after 4 weeks of ACE inhibitor administration. Laboratory data were obtained 1) just before the ACE inhibition, 2) after 4 weeks of the ACE inhibitor single treatment, and 3) after another 4 weeks of the additional treatment with camostat mesilate. The urinary protein excretion decreased from 1) 10.1 +/- 1.3 to 2) 7.3 +/- 1.1, and 3) 4.6 +/- 0.9 g/day [mean +/- SEM; significance of difference 1) 2), p less than 0.05; 2)-3), p less than 0.01], and the serum total protein values increased from 1) 5.0 +/- 0.3 to 2) 5.2 +/- 0.2, and 3) 5.4 +/- 0.3 g/dl [1)-3), p less than 0.05]. The plasma levels of fibrinogen, and of E fragment and D-dimer of FDP changed from 1) 476 +/- 43 to 2) 477 +/- 41, and 3) 374 +/- 33 mg/dl [2)-3), p less than 0.01], from 1) 125 +/- 19 to 2) 147 +/- 27, and 3) 104 +/- 30 ng/ml [2)-3), p less than 0.05], and from 1) 261 +/- 60 to 2) 272 +/- 86, and 3) 185 +/- 56 ng/ml [2)-3), p less than 0.05], respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635287 TI - Study of factors related to hypotension in hemodialysis patients. AB - The factors related to hypotension in hemodialysis patients were evaluated. The subjects consisted of 120 hemodialysis patients (61 males and 59 females), whose ages ranged between 28 and 82 years, and who had undergone hemodialysis treatment for a period ranging between 3 and 201 months. They were divided into three groups: Group A, 53 normotensive patients; Group B, 52 patients with hypotension during hemodialysis; and Group C, 15 patients with constant hypotension. The evaluated factors were age, sex, etiology of renal failure, hemodialysis term, ultrafiltered volume, responsiveness to vasopressor drugs, Cr, Na, Ht, TP, cardiothoracic ratio, presence or absence of heart disease, and microvibration pattern. Statistical analysis was performed using multivariate analysis (Quantification II and IV methods). The results of the Quantification IV method indicated that Groups A and B were similar but Group C was quite different from the other two groups. The results of the Quantification II method indicated that the most important factor which characterized the difference between Group A and Group C was the responsiveness to vasopressor drugs, and the most important factor in the difference between Group B and Group C was the microvibration pattern. Group B was characterized by abnormal microvibration patterns and Group C was characterized by a low responsiveness of the peripheral vessels to vasopressor drugs. We conclude that the hypotension during hemodialysis was caused predominantly by dysfunction of the autonomic nervous system, while the constant hypotension was caused predominantly by a deterioration of constriction of the peripheral vessels. PMID- 1635285 TI - Comparison of converting enzyme inhibitor and calcium channel blocker in SHR with nephrotoxic serum nephritis. AB - In order to compare the protective effects of angiotensin converting enzyme inhibitors (ACEI) and calcium channel blockers (CCB) on the renal function in experimental nephritis, nephrotoxic serum nephritis was induced in male spontaneously hypertensive rats (SHR). The above drugs were then chronically administered to different groups, as follows: the ACEI-treated group (n = 7) received captopril (150 mg/kg/day), and the CCB-treated group (n = 6) was given both nifedipine (40 mg/kg/day) and nisoldipine (20 mg/kg/day). The control group (n = 8) received a placebo. Although the control group developed marked hypertension and proteinuria, the rats treated with either ACEI or CCB demonstrated a significant and equivalent decrease in mean arterial pressure and urinary protein excretion. At 15 weeks after the injection of nephrotoxic serum, all rats were anesthetized with Inactin, and the glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured. In the control group, GFR and RPF were markedly attenuated. However, both were preserved at much higher levels in the ACEI-treated group, and GFR was also maintained to a similar degree in the CCB treated group. Histological studies were carried out after the clearance studies. As a result, it was found that the ACEI treatment significantly limited the development of glomerulosclerosis, whereas CCB modestly ameliorated the glomerular structural lesions. Moreover, ACEI significantly reduced the serum cholesterol, while CCB did not exert such an effect. These results suggest that both ACEI and CCB have a therapeutic effect in experimental glomerulonephritis models which are accompanied by hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635288 TI - A case of IgA nephritis showing diffuse podocytic detachment from the glomerular basement membrane. AB - We report the case of a 15-year-old Japanese female with severe mesangial proliferative IgA glomerulonephritis who showed a dramatic response to cocktail therapy for nephrotic syndrome. She had suddenly developed massive proteinuria and microscopic hematuria. The first renal biopsy at one month after onset revealed severe mesangial hypercellularity and podocytic detachment from the glomerular basement membrane (GBM). The cocktail therapy resulted in a decrease of proteinuria clinically, and a second biopsy demonstrated repair of the podocytic detachment. We suggest that the massive proteinuria in this case was due to destruction of the size barrier by detachment of podocytes from the GBM, and the repair of the podocytic covering on the GBM was accelerated by the cocktail therapy. PMID- 1635289 TI - Timolol movement across isolated iris-ciliary body of albino rabbit. AB - The outward (from the aqueous to the stromal side) and the inward (from the stromal to the aqueous side) movement of [14C]timolol across the isolated iris ciliary body of the albino rabbit were studied using Ussing's chamber under short circuit conditions and timolol concentrations of 0.025-60 microM. The tissue permeability in both directions decreased gradually as the timolol concentration was increased, while at higher concentrations tissue permeability was almost constant. This finding indicated that the timolol movement in both directions consists of passive diffusion and a possibly active mechanism, with the former contributing mainly at higher concentrations. The tissue permeability for passive diffusion was calculated as 7.2 x 10(-6) cm/second. The outward timolol movement by a possibly active mechanism was saturated against the concentrations tested. In addition, the outward timolol movement was significantly reduced by ouabain, 2,4-dinitrophenol and low temperature. These results suggested that the non passive component of the outward timolol movement was carrier-mediated active transport, and Lineweaver-Burk plots gave the half-saturation concentration (Km) value of 0.098 microM. On the other hand, the inward timolol movement by a possible active mechanism was not saturated. Neither ouabain nor 2,4 dinitrophenol inhibited it. Thus the non-passive component of the inward timolol movement was thought to be different from that of the outward movement. PMID- 1635290 TI - Molecular mimicry: uveitis induced in Macaca fascicularis by microbial protein having sequence homology with retinal S-antigen. AB - S-antigen (S-Ag), a well characterized 45-kDa protein in the photoreceptor cells, induces predominantly T-cell-mediated autoimmune uveitis when injected into experimental animals. Recently, we have shown that native histone H3 protein derived from yeast (Saccharomyces cerevisiae), or a synthetic peptide that is homologous with S-Ag peptide M in having six consecutive amino acids, induces experimental autoimmune uveitis (EAU) similar to that induced by native S-Ag in the Lewis rat. In this study, monkeys (Macaca fascicularis) immunized with histone H3 peptide developed a strong cellular immune response to this peptide as well as to peptide M. However, no significant inflammation or hypervascularization was observed in the retina or the iris during the experimental period, when they were examined clinically with an inverted ophthalmoscope. Histopathological examination showed that all monkeys injected with histone H3 peptide or with native histone H3 lost a large number of photoreceptor rod cells and developed neovascularization in the outer nuclear cell layer of the retina. These histopathological findings in the monkey retina closely resemble those seen in human patients with some types of uveitis. The possible involvement of microbial proteins having sequence homology with normal retinal proteins in the pathogenicity of human uveitis is discussed. PMID- 1635291 TI - Study of suppressive effect of intravenous fluconazole on endogenous Candida endophthalmitis in rabbits. AB - The effect of intravenous fluconazole on endogenous Candida endophthalmitis in rabbits was investigated. Preventive and therapeutic experiments were carried out. In the preventive series, rabbits were injected intravenously with 5 mg/kg of fluconazole at 30 minutes, 1 day and 2 days after intravenous inoculation with Candida albicans spores. The control group received no medication. No treated rabbits developed ocular lesions and no Candida spores were isolated from the treated eyes. On the other hand, all control rabbits developed bilateral chorioretinitis and C. albicans was isolated invariably from the control eyes. In the therapeutic series, intravenous fluconazole (5 mg/kg body weight) was administered from 3 to 6 days after inoculation. All rabbits developed chorioretinitis and Candida spores were isolated from all eyes. Therefore, the results of this study prove that intravenous fluconazole is more effective in preventive use than in therapeutic use against endogenous Candida endophthalmitis in rabbits. PMID- 1635292 TI - Expression of human ornithine aminotransferase (OAT) in OAT-deficient Chinese hamster ovary cells and fibroblasts of gyrate atrophy patient. AB - Gyrate atrophy is a hereditary chorioretinal degenerative disease caused by a deficiency of the mitochondrial enzyme, ornithine aminotransferase (OAT). Recent investigations have demonstrated the molecular genetic defects of OAT in gyrate atrophy patients. We constructed a eukaryotic expression vector (pcDHOAT) which contains the SV40 promoter and human OAT cDNA. We used OAT(-) Chinese hamster ovary (CHO) cells, which have negligible OAT activity, and fibroblasts from a gyrate atrophy patient (GA35 cell), which have negligible OAT mRNA and enzyme. Incorporation of pcDHOAT and synthesis of human OAT mRNAs and active enzyme were demonstrated in both cell types. The level of expression of human OAT was low in the GA35 cells in comparison to the CHO cells. Despite the limited success, the ability to express active OAT in these OAT-deficient cells using an expression vector offers possibilities of replacement gene therapy for gyrate atrophy. PMID- 1635293 TI - Linkage disequilibrium between glucose-6-phosphate dehydrogenase deficiency and congenital color blindness in Turkish population. AB - No erythrocyte glucose-6-phosphate dehydrogenase (G6PD)-deficient person was detected among 90 male patients with congenital color blindness (CCB) diagnosed at the Ophthalmology Clinic of our Hospital. Eighteen complete G6PD-deficient subjects had normal color vision. These results suggest that there is a linkage disequilibrium between CCB and G6PD genes. PMID- 1635294 TI - Characterization of T-cell subsets, soluble interleukin-2 receptors and interleukin-6 in Vogt-Koyanagi-Harada disease. AB - The lymphocyte subunits and subsets of 12 patients with Vogt-Koyanagi-Harada disease (VKH disease) were characterized using two-color flow cytometry techniques, both in cerebrospinal fluid (CSF) and in peripheral blood (PB). Soluble interleukin-2 receptor (sIL-2R) levels and interleukin-6 (IL-6) levels were also measured. The percentage of T cells was significantly higher in CSF than in PB (P less than 0.01), but the percentage of B cells was decreased in CSF (P less than 0.05). As for T-cell subsets, the percentage of helper T cells was especially high in CSF (P less than 0.01). Also, the ratio of helper T cells/suppressor T cells was significantly larger in CSF than in PB. These data suggest that helper T cells play an important role in the early stages of VKH disease. sIL-2R and IL-6 levels were not elevated in CSF of patients with VKH disease. The level of sIL-2R in serum also was not elevated. PMID- 1635295 TI - Photocoagulation with continuous wave ND:YAG laser for neovascular maculopathy. AB - Twenty-two eyes in 22 cases of neovascular maculopathy were treated with continuous wave (CW) Nd:YAG laser and followed up for 6 to 24 months. The effect of the treatment was evaluated by repeated visual acuity testing, fundus photography, fluorescein angiography and automated static perimetry. In 91% of the patients visual acuity remained unchanged or improved. Fluorescein angiography revealed that the neovascularization disappeared in 91% of the patients. In 40% of the patients the central visual field showed improvement by automated static perimetry. These results indicate that CW Nd:YAG laser photocoagulation is useful for the treatment of neovascular maculopathy. PMID- 1635296 TI - High frequency of mitochondrial ND4 gene mutation in Japanese pedigrees with Leber hereditary optic neuropathy. AB - The association of the ND4 gene mutation (mutation) at nucleotide position 11778 of mitochondrial DNA (mtDNA) was investigated in 14 definitive Japanese pedigrees with Leber hereditary optic neuropathy (LHON). The mutation was detected by SfaNI and MaeIII restriction fragment length polymorphisms of mtDNA amplified by polymerase chain reaction. All 14 LHON pedigrees exhibited the mutation, whereas 10 controls did not. The association of this mutation with LHON was revealed to be significantly higher in Japanese (91.7%) than in 27 reported Caucasian (51.9%) LHON pedigrees, implying genetic heterogeneity. In the tested 14 pedigrees, 28 cases with the mutation comprised 19 affected (17 male and 2 female) and 9 asymptomatic (all female except for one) individuals. Such a predominance of males in the incidence of LHON suggested probable participation of additional pathogenetic factor(s) in the development of optic atrophy in LHON patients. PMID- 1635297 TI - Cell death in rat retina after pressure-induced ischaemia-reperfusion insult: electron microscopic study. II. Outer nuclear layer. AB - Pressure-induced ischaemia-reperfusion insult of sufficient duration leads to significant retinal damage in rats. In this report we describe the morphology of degenerating cells in the outer nuclear layer at several time points after the insult, as observed by electron microscopy. Only one death pattern was observed. It was characterized by asynchronous involvement of individual cells, progressive densification and shrinkage of nuclear and cytoplasmic components, and a final phase of disaggregation and heterophagic elimination by Muller cells. This pattern of cell death combined features of an apoptosis-like mechanism and secondary necrosis. PMID- 1635298 TI - Clinical features of Japanese family with autosomal dominant retinitis pigmentosa caused by point mutation in codon 347 of rhodopsin gene. AB - Four members in a Japanese family had autosomal dominant retinitis pigmentosa caused by a single point mutation in codon 347 of the rhodopsin gene. The youngest, an 11-year-old girl, had an abnormal electroretinographic response, although her fundus appeared normal. The other affected family members noticed night blindness in the second decade. Their fundi showed diffuse pigmentation with concentric visual field loss, and there was no recordable electroretinographic response. Cataract developed in the fourth decade in the older patients. Good visual acuity was retained however, even in the fifth decade, after cataract extraction. These clinical features were similar to those of American patients (European family origin) with the same mutation of the rhodopsin gene reported previously. PMID- 1635299 TI - Uric acid as biochemical marker for retinal and optic nerve damage after occlusion and reperfusion of common carotid and vertebral arteries in rat. AB - Transient retinal and optic nerve ischemia lasting for 20 minutes was produced in Wistar rats by clipping bilateral common carotid arteries and coagulating both vertebral arteries by heat. The uric acid level in the retina and optic nerve were determined by high performance liquid chromatography with electrochemical detection just before induction of ischemia, 20 minutes after induction of ischemia, and after resolution of ischemia. Uric acid content in the optic nerve (28.0 +/- 4.5 ng/mg protein) was about 5 times higher than that in the retina (5.7 +/- 0.8 ng/mg protein) in the control experiment. Ischemia lasting for 20 minutes caused a 2.7-fold increase of uric acid in the optic nerve and a 1.8-fold increase in the retina. Following reperfusion of the blood flow by unclipping of the common carotid arteries, the uric acid level decreased to the control level in both the retina and optic nerve 30 minutes after unclipping, which was followed by 3.1- and 1.6-fold increases in uric acid in the retina and the optic nerve, respectively, at 60 minutes after unclipping. Although ischemia alone causes tissue damage, there is some clinical evidence that greater injury can occur after oxygen is reintroduced to ischemic tissue. Our results indicate that the retina is more likely to be damaged by reperfusion than the optic nerve. PMID- 1635300 TI - Increased lysosomal enzyme activity of keratocytes after endocytosis of foreign particles. AB - It has been reported that keratocytes endocytose foreign particles both in vitro and in vivo, suggesting the active participation of keratocytes in corneal wound healing and host defense mechanism. To understand the cellular response and the fate of engulfed foreign particles, we investigated the changes in the lysosomal enzyme activities after keratocytes endocytosed latex beads or glutaraldehyde fixed Staphylococcus aureus. Acid phosphatase activity in the cells endocytosing either latex beads or fixed bacteria increased significantly as compared with that in the control over the period of 12 hours. Changes in acid phosphatase activity depended on both the incubation periods and the amount of latex beads or bacteria added. The activity reached a plateau after 6 hours of incubation. When keratocytes endocytosed latex beads, the activity of N-acetyl-beta-D glucosaminidase in the cells showed an increase similar to that of acid phosphatase. However, the N-acetyl-glucosaminidase activity in the cells endocytosing fixed bacteria did not increase significantly. These findings suggest that endocytosing keratocytes increase degrading enzyme activities in the cells to break down engulfed foreign particles. It is also suggested that the intracellular response is varied according to the character of the engulfed materials. PMID- 1635301 TI - Batten disease--deteriorating course of ocular findings. AB - For over two years, we monitored the visual functions and ocular findings of two siblings with Batten disease. At the initial visit, the older patient was in the advanced stage of the disease, manifesting symptoms similar to those previously reported by many authors. The younger patient, on the other hand, was in the early stage of the disease at the time of the first visit. In the next 8 months, however, the visual acuity of the younger patient decreased rapidly, from 1.0 to below 0.1. Although the electroretinogram (ERG) showed a normal a-wave and a reduced b-wave when visual acuity was normal, repeated recordings of the ERG at each visit revealed rapid reduction of the b-wave. This finding seems to confirm the animal data, indicating that the primary lesion of the retina was in the inner layers. To our knowledge, this is the first report on these phenomena which may be unique to the deteriorating visual system in Batten disease and may facilitate early diagnosis. PMID- 1635302 TI - Bilateral retinal detachment with large breaks of pars plicata associated with coloboma lentis and ocular hypertension. AB - A 39-year-old man developed bilateral, insidiously progressing detachment of the retina and nonpigmented epithelium of the ciliary body because of a large break in the pars plicata. The anterior segments had multiple malformations including ectopia of the lens associated with coloboma of the lens and hypoplastic ciliary processes. The pars plicata breaks were present in areas corresponding to the anomalies of the lens-zonule-ciliary body complex and caused progressive, shallow rhegmatogenous retinal detachments with anterior chamber cells and elevation of intraocular pressure. Surgeries with scleral buckling procedure combined with vitrectomy and lensectomy brought about reattachment of the retina. This case indicates that subtle anomalies in the lens-zonule-ciliary body complex might be an indication of a break in the nonpigmented epithelium of the ciliary body which could lead to rhegmatogenous retinal detachment. The mode of inheritance of the clinical syndrome remained undefined because of negative family history. PMID- 1635303 TI - A case of testicular feminization syndrome with bulimia nervosa. AB - A 19-year-old patient with a female appearance visited our department for treatment of bulimia nervosa. The patient had primary amenorrhea. Chromosomal studies revealed a 46XY karyotype, and the plasma testosterone level was in the range of normal adult males. The patient was diagnosed as having testicular feminization syndrome. The psychological background, such as severe anxieties concerning her body, was behind the eating disorders. Examinations revealed intraabdominal testes. A bilateral gonadectomy was performed, and no androgen receptors were detected in the suprapubic skin. After the gonadectomy, the patient's mental status became much more stable, and the ability to control her eating pattern was restored. Testicular feminization with bulimia nervosa is rare in Japan. The importance of mental support and a careful follow-up to people with testicular feminization is being discussed. PMID- 1635304 TI - Reduction of cerebral blood flow in chronic schizophrenia: relation to age. AB - The effect of age on resting-state cerebral blood flow (CBF) was studied in 40 medicated patients with chronic schizophrenia aged 20 to 57 and 32 age- and sex matched normal controls, using the regional CBF with the xenon-133 inhalation technique. Global CBF (average of 16 cerebral regions) and the left prefrontal flow ratio (left prefrontal/global CBF) were significantly lower in schizophrenics aged 20-29 than in age-matched controls. Both global CBF and the left prefrontal flow ratio correlated with age in controls, but neither of such correlations was found in schizophrenics. Therefore, the CBF deficits in chronic schizophrenia appear to be unaffected by the aging process. PMID- 1635305 TI - Linkage study of schizophrenia with markers on chromosome 11 in two Japanese pedigrees. AB - We examined the linkage between schizophrenia and DNA markers on chromosome 11 in two Japanese pedigrees. Thirty individuals from the two pedigrees were genotyped at the eleven polymorphisms (eight loci) studied. Data were analyzed according to three models, representing a range of single gene models from near dominant to an intermediate model. For all markers, except those at the D11S35 locus, there is no evidence for the linkage. Positive LOD scores between 1 and 1.5 are obtained for some genetic models with the polymorphism at D11S35. Two point scores for the broad diagnostic model and for the intermediate parameter set peak at 1.49. PMID- 1635306 TI - 5HT2 receptor-mediated function in depressed patients: investigation by measuring 5HT-induced shape change of blood platelets. AB - The 5HT-induced shape change (5HT-SC) of blood platelets, which had been suggested to reflect the 5HT2 receptor-mediated function of the central nervous system (CNS), was examined in patients with depression before or after antidepressant therapy. The degree of 5HT-SC did not differ between patients before treatment (n = 17) and healthy controls (n = 26). In patients after treatment (n = 12), in whom depression had been improved but drug therapy was continued, 5HT-SC in a concentration of 10(-5) M 5HT was observed more potently than that in healthy controls or untreated patients (p less than 0.05 and p less than 0.05, respectively). In 4 patients in whom 5HT-SC was measured before and after mianserin treatment, 5HT-SC increased after the treatment. These results suggest that the 5HT2 receptor-mediated function in the CNS may not be damaged in patients with depression, and that the 5HT2 receptor-mediated function in the CNS may be enhanced by antidepressants. PMID- 1635307 TI - Serial changes of SPECT in periodic synchronous discharges in a case with Creutzfeldt-Jakob disease. AB - We conducted serial EEG and SPECT studies on one female with Creutzfeldt-Jakob disease (CJD). In an analysis of EEG, a periodic synchronous discharge (PSD) was observed in the middle of the third stage (terminal stage) of Bernoulli's classification. The frequency of PSD was the highest at the beginning of the third stage, followed by a gradual decrease and disappeared at the end of the third stage. In the middle of the third stage, SPECT disclosed blood flow differences between the cerebrum and other regions (the cerebellum and the brainstem), while no such difference was observed by SPECT at the end of the third stage. It was suggested that the appearance of PSD requires the presence of a pathological change in the cerebrum precedent to other regions. PMID- 1635308 TI - Voiding dysfunction in Parkinson's disease. AB - A micturitional history of unselected 110 patients with Parkinson's disease revealed that 66 (60%) had urinary symptoms such as irritative in 28%, obstructive in 11%, and both symptoms in 21%. The frequency of urinary symptoms statistically correlated with severity of the disease, but not with the duration of illness and no sexual difference was noted. A urodynamic study was conducted in 39 patients and 7 had residual urine of 30 ml or more, 19 had detrusor hyperreflexia, 19 had a small bladder capacity and only 1 had detrusor-sphincter dyssynergia. The results indicate that the disturbed urine storage is more frequent and to a severer degree than that of urine evacuation in Parkinson's disease. PMID- 1635309 TI - Proceedings of the 6th Workshop for the Clinical Research on Chronobiology. October 16-17, 1991, Nagoya. PMID- 1635310 TI - Sleep rhythm disturbances in school refusers. PMID- 1635311 TI - Circadian sleep-waking rhythm disturbance in blind adolescence. PMID- 1635312 TI - Free-running melatonin, sleep propensity, cortisol and temperature rhythms in a totally blind person. PMID- 1635313 TI - Three cases with sleep-wake rhythm disorders, showing remarkable improvements in daily cycle under the influence of several psycho-social conditions. PMID- 1635314 TI - Seasonal affective disorder (SAD) with non-24-hour sleep-wake rhythm during depressive phase. PMID- 1635315 TI - Study on sleep-wake rhythm disorders in two outpatient clinics. PMID- 1635316 TI - A polysomnographic study on patients with delayed sleep phase syndrome (DSPS). PMID- 1635317 TI - Effect of vitamin B12 (mecobalamin) on the free-running period of rat circadian behavioral rhythm. PMID- 1635318 TI - Effects of vitamin B12 on the period of free-running rhythm in rats. PMID- 1635319 TI - Effect of methylcobalamin (VB12) injection on sleep-wake rhythm in demented patients. PMID- 1635320 TI - A multicenter study of the effects of vitamin B12 on sleep-waking rhythm disorders: in Shizuoka Prefecture. PMID- 1635321 TI - Collaborative multicenter field trial of the Draft of ICD-10 in Japan- interdiagnostician reliability and disagreement: a report from the WHO project on "field trials of ICD-10, Chapter V". AB - The Draft of "ICD-10, Chapter V, Clinical Descriptions and Diagnostic Guidelines" was tested in a multicenter field trial in Japan. We have previously reported good results in suitability, confidence and ease of diagnosis, and adequacy of descriptions of the Draft. In this paper, the interdiagnostician reliability of the Draft is reported. Among the two-character categories, "Schizophrenia, Schizotypal States and Delusional Disorders (F2)" (ICC = .80) and "Mood Disorders (F3)" (ICC = .80) proved reliable. "Neurotic, Stress-Related, and Somatoform Disorders (F4)" was less reliable (ICC = .65). The ICCs of the 17 major categories (three-character code) and the 21 subcategories (four-character code) were also calculated. The finding that in Japan subtyping schizophrenia with ICD 10 was more reliable than that made using DSM-III Diagnostic Criteria supports the need to use a descriptive version of ICD-10 as the basis for several versions serving different purposes. The nature of disagreements with unreliable categories was also investigated. The results are discussed with special reference to the changes in the final Draft of Chapter V, which contained a feedback of the results from field trials from all over the world. PMID- 1635322 TI - A multicenter study on sleep-wake rhythm disorders in Japan: a preliminary results. PMID- 1635323 TI - The factors in influencing the adjustment to shift work. PMID- 1635324 TI - Diurnal rhythm in body temperature in different phases of the menstrual cycle. PMID- 1635325 TI - Ultradian rhythms in task performance and EEG activities during prolonged continuous work. PMID- 1635326 TI - Effects of phototherapy on circadian rhythms of body temperature in affective disorders. PMID- 1635327 TI - Circadian temperature and sleep-wake rhythms in depression. PMID- 1635328 TI - Fifty young women's seasonal changes in mood and behavior in Tokyo. PMID- 1635329 TI - Prevalence of seasonal mood changes in low latitude area: Seasonal Pattern Assessment Questionnaire score of Quezon City workers. PMID- 1635330 TI - A case of reversed seasonal affective disorder. PMID- 1635331 TI - Seasonal variations of the circadian rhythms in seasonal affective disorder (2). PMID- 1635332 TI - A nationwide survey of seasonal affective disorders in outpatient university clinics in Japan--a preliminary report. PMID- 1635333 TI - Four clinical types of panic disorders. AB - The authors attempted to classify panic disorders into four types according to a clinical course and accompanying neurotic or depressive symptoms. The characteristics of each type are as follows; type I: a single panic attack is the only symptom, type II: only panic attacks occur frequently without any accompanying neurotic or depressive symptoms, type III: a recurrence of panic attacks and the gradual development of neurotic symptoms, such as anticipatory anxiety, generalized anxiety, agoraphobia, or hypochondriasis, type IV: depressive symptoms develop in the course of recurring panic attacks. Type IV is further divided into three subtypes. Type IV-1: depressive symptoms develop secondary to panic attacks and major depression later coexists with panic disorder. Type IV-2: panic disorder continuously changed into major depression. Type IV-3: panic attacks and depressive symptoms are seen independently. The most common types are type III and type IV-1, and seem to be a core group of the panic disorder. Typical cases of each type are presented and underlying psychopathology is discussed. PMID- 1635334 TI - Current views on panic disorder and its management in Japan: a national survey. AB - In a national random-sample survey, the views of 1,069 practicing clinicians, including internists, surgeons and psychiatrists, on panic disorder were surveyed by using a series of questionnaires. In spite of a high rate of clinical experience and agreements on the symptoms among clinicians, the nature of this disorder, such as a common descriptive diagnosis, and the preferred treatment have not been agreed upon by the Japanese medical community. Furthermore, respondents were questioned as to the preferred treatment for panic disorder, but no treatment was regarded as critical by a majority of clinicians. It is concluded that because of the high potential patient population with panic disorder, clinical research that will provide more adequate diagnosis and treatment for this disorder is necessary in Japan. PMID- 1635335 TI - Outcome at discharge for clients in a psychiatric day care program. AB - The effectiveness of a psychiatric day care program was assessed in terms of the outcome at discharge for 79 clients. One-third of the clients were employed, either full-time or part-time (in case of students, at school), during the postprogram period of three months or more. Another one-third left the program prematurely with or without exacerbation of psychotic symptoms. Clients having premature termination were significantly less adherent to outpatient clinic visits and/or psychotropic medication. Family's understanding of and cooperation in the program were significantly less favorable in clients with early termination. The possible strategies for reducing the dropouts were discussed. PMID- 1635336 TI - Klinefelter's syndrome and epileptic psychosis: a case report. AB - We present here a case of Klinefelter's syndrome with epileptic psychosis. The patient was a 30-year-old male, who suffered from epilepsy for 23 years. He showed auditory hallucination, delusion of reference and delusion of grandeur. At present there are some cases of Klinefelter's syndrome with various psychiatric symptoms, but there are few cases of Klinefelter's syndrome with epileptic psychosis. These various neuropsychiatric symptoms of the present case are thought to be associated with a specific effect of chromosomal abnormality through the cerebral dysfunction. PMID- 1635337 TI - On the psychophysiology of dreaming: a sensory image--free association hypothesis of the dream process. AB - A psychophysiological hypothesis of the dream process during REM sleep called "a sensory image-free association hypothesis" is proposed. It is assumed that a state with a sustained EEG pattern of drowsiness (non-REM stage-1) and muscle atonia produces a stream of disorganized and vague thinking as a background mentation during the REM sleep. The phasic excitation of the brain occurring concurrently with the burst of rapid eye movements (REMs) activates the hippocampal-neocortical memory system and draws out sensory images from the memory reservoir of the brain. The dreamer makes a freely organized association about the successive sensory images and makes up a dream story. This hypothesis is compatible not only with the recent neurophysiological findings but also with traditional psychological interpretation of the dream content. PMID- 1635338 TI - A computerized tomographic study in patients with delusional and non-delusional depression. AB - This is a description of a computerized tomographic study of 45 non-delusional depressed, 29 delusional depressed patients and 77 neurotic control subjects. The cerebral atrophy ratio (CAR) on the three different slices and the ventricular ratio (VBR) of the anterior horn and the body of the lateral ventricles were calculated, analyzed and compared using Student's t test. Compared to the control subjects, the non-delusional depressive patients had greater CAR values than the controls but there were no significant differences of VBR values between the two groups. The patients with delusional depression had significantly larger CAR and VBR values than the non-delusional depressives and control subjects. The delusional depressives had greater brain atrophy than the non-delusionals and it was suggested that organic cerebral factors may have etiological significance in the depressions, especially the delusional depressives. PMID- 1635339 TI - The peritoneal equilibration test in children. AB - The peritoneal equilibration test (PET) has been recommended in adults as a standardized means of estimating solute transport. Based on results of the PET, adult peritoneal permeability has been classified as high, high average, low average, and low. We performed a PET on 32 children aged 0.8 to 17.8 years (mean 9.3) using a dwell volume of 32 +/- 5 ml/kg of 2.5% dialysate. Dialysate to plasma (D/P) ratios for creatinine, urea, and sodium were calculated at two and four hours as were the ratios of dialysate glucose at two and four hours to the dialysate glucose at time 0 (D/Do). Stepwise logistic regression identified only the patients' age and D/Do glucose values at two hours as significant predictors of ultrafiltration. Net ultrafiltration after a four hour dwell could be predicted for 75% of children above 9.3 years, or whose D/Do glucose value at two hours was greater than 0.45. The mean and standard deviation values for D/Do glucose and D/P creatinine at four hours were 0.31 +/- 0.17 and 0.71 +/- 0.12, respectively. When children are characterized according to adult standards, at least 70% fall into the high or high average permeability categories. PMID- 1635340 TI - Glomerular hemodynamics and eicosanoid synthesis in a rat model of IgA nephropathy. AB - We sought to study glomerular pathophysiology in a model of IgA nephropathy (IgAN). Preliminary experiments with oral immunization indicated that Lewis rats had higher IgA levels and IgA/IgG ratios than Wistar, Fischer or Sprague-Dawley rats. Six groups of Lewis rats were studied: four continuously orally immunized for eight weeks with bovine gamma globulin (BGG) in the drinking water, the other two non-immunized controls. Groups of immunized rats were treated with a thromboxane receptor antagonist (SQ 29,485) and/or a thromboxane synthase inhibitor (UK 38,485). After systemic challenge, microscopic hematuria was present in 84% of immunized rats not given anti-thromboxane drugs versus 18% of non-immunized rats (P less than 0.01). Immunized rats showed predominantly IgA glomerular deposits with lesser IgG and C3, and produced more glomerular thromboxane than controls, but no significant increase in prostaglandin E2. Immunized rats also had reduced GFR and RPF, but not a reduced filtration fraction, compared to controls. Thromboxane synthase inhibitor diminished glomerular thromboxane and increased prostaglandin E2 in immunized rats. Anti thromboxane therapy reduced hematuria and apparently re-established the RPF but not the GFR in immunized rats, yielding a reduced filtration fraction. We propose that increased thromboxane, in concert with mesangial contraction that is unaffected by anti-thromboxane drugs, contributes to the pathophysiology in this model of IgAN. PMID- 1635341 TI - Distribution of the alpha 1 and alpha 2 chains of collagen IV and of collagens V and VI in Alport syndrome. AB - We compared the distribution of the alpha 1 and alpha 2 chains of collagen IV and of collagens V and VI in glomeruli of males with Alport syndrome to their distribution in normal glomeruli and glomeruli from patients with non-Alport renal diseases. alpha 1(IV), alpha 2(IV), collagen V and collagen VI are normally restricted to the mesangium and the subendothelial aspect of the glomerular basement membrane (GBM). In contrast, these proteins were present throughout the entire width of the GBM in Alport glomeruli. These alterations were apparent in "early" Alport glomeruli, that is, those exhibiting minimal abnormalities by light microscopy, and they were further accentuated in sclerosing Alport glomeruli. Obsolescent Alport glomeruli, in which the capillary tuft had collapsed and few remaining cell nuclei were present, exhibited nearly complete loss of alpha 1(IV) and alpha 2(IV), like obsolescent glomeruli in non-Alport diseased kidneys. However, the matrix of obsolescent Alport glomeruli stained intensely for collagen V and collagen VI, while these collagen types were not prominent in obsolescent glomeruli of non-Alport diseases kidneys. These observations suggest that the process of glomerulosclerosis in Alport kidneys has attributes unique to this disease. It would also appear that mutations affecting the Alport gene product have secondary effects on the distribution of other GBM constituents. PMID- 1635342 TI - Glomerulonephritis in chronic lymphocytic leukemia and related B-cell lymphomas. AB - We retrospectively analyzed clinical presentation, immunopathological data and renal outcome in 13 patients with glomerulonephritis (GN) and chronic lymphocytic leukemia (CLL) or related diffuse well-differentiated lymphocytic lymphoma (WDLL) of B-cell lineage. B-cell proliferation and glomerulopathy were simultaneously diagnosed in seven of the 13 patients. Nephrotic syndrome was observed in nine patients. Serum creatinine was elevated (greater than 120 mumol/liter) in 10 patients and exceeded 400 mumol/liter in three patients. A clear cut relationship between GN and hematologic disease could be established in nine cases: five patients had MPGN caused by type I or type II cryoglobulinemia; two had MPGN or mesangial hypertrophy with circulating and deposited noncryoprecipitating monoclonal IgG K and IgM K, respectively; in the two remaining patients, monotypic IgG K glomerular deposits exhibiting fibrillary organization were observed in association with MGN or MPGN, despite the absence of circulating M component by immunofixation. The pathophysiologic link between glomerular lesions and B-cell proliferation was further evidenced by effectiveness of specific treatment of the malignancy by chlorambucil. This drug, used in the absence of steroids, induced complete remission of nephrotic syndrome in the five patients to whom it was given. Moreover, in the five patients with creatininemia greater than 200 mumol/liter who received chemotherapy, substantial improvement in renal function was observed. These overall data demonstrate that the occurrence of GN in B-CLL and related lymphoma is not fortuitous, and testify to the paraneoplastic nature of glomerular involvement mediated by deposition and possibly processing of cryoprecipitating or noncryoprecipitating M-components. PMID- 1635343 TI - Glomerular damage after uninephrectomy in young rats. I. Hypertrophy and distortion of capillary architecture. AB - Uninephrectomy (UNX) results in a higher incidence of focal glomerular sclerosis (FGS) in young rats than it does in adults. The reason for this higher susceptibility in young animals is not fully understood, but this does suggest that UNX in young rats may represent a particularly promising model in which to study the development of FGS. In the present study 10-day-old rats were subjected to UNX. After 4, 12 and 24 weeks, glomerular hypertrophy, structural lesions and function were analyzed in comparison with sham-operated controls. Up to the twelfth week, remnant kidney growth and glomerular growth proceeded in parallel; thereafter, kidney growth ceased, whereas glomerular growth continued undiminished. Twenty-four weeks after UNX, glomerular tuft volume in experimental animals exceeded that in controls by 80%. Twelve weeks after surgery, total GFR in UNX rats was approximately 80% of that in controls, a value maintained until the end of the observation period. Twenty-four weeks after surgery, heavy proteinuria was present in UNX animals. Structural abnormalities in glomeruli of UNX animals were already encountered 12 weeks after surgery; they were present to a much lesser extent in controls. In UNX animals these proceeded to the FGS stage by the end of the observation period. Three major groups of glomerular lesions were observed: (1) changes in the width and shape of glomerular capillaries. (2) changes in podocyte structure, and (3) tuft adhesions to Bowman's capsule with or without segmental sclerosis. The structural changes are analyzed in this and an accompanying paper [1]. The present paper deals with the widespread formation of irregular, giant capillary loops. They occur predominantly at the tuft periphery with a clear predilection for the vascular pole region. They are not a result of compensatory growth, but rather an expansion of single capillaries due to failure of the mesangium. Local disconnection of the mesangium from its anchoring points at the GBM leads to bulging and "coalescence" of capillary loops, resulting in abnormally-shaped vascular channels. This process is associated with a rearrangement of the corresponding mesangium. In our view, the appearance of dilated capillaries represents a local event pivotal to the development of more severe lesions, such as tuft adhesions and FGS. PMID- 1635344 TI - Glomerular damage after uninephrectomy in young rats. II. Mechanical stress on podocytes as a pathway to sclerosis. AB - In a preceding study [1], we showed that within six months after UNX in young rats, glomeruli in the remnant kidney undergo a sequence of serious changes which finally lead to focal segmental glomerulosclerosis (FGS). The formation of abnormally-shaped capillary channels was shown to result from local mesangial failure and is considered to be a nidus for the development of more severe lesions. In the present paper, the development of characteristic lesions in podocyte structure is described and analyzed. Concomitant with overall glomerular growth after UNX, a pronounced hypertrophy of podocytes was observed, while the mean number of podocytes per glomerulus did not change. It appears that podocytes cannot sustain the same degree of growth as the tuft as a whole; podocyte hypertrophy is soon followed by maladaptive changes which eventually lead to cell destruction. The following sequence of pathologic changes can be suggested: cell bodies enlarge in volume and area associated with a dramatic attenuation to cytoplasmic sheets. Primary processes are thinned out and frequently extend to remote capillaries. As a whole, the capillary area served by a single podocyte is dramatically enlarged. Furthermore, the expanding cytoplasmic sheets (derived from podocyte cell bodies) cover an increasingly large proportion of the outer capillary surface, that is, of the filtration area. Consequently, an increasing amount of filtrate is delivered into the subcellbody space. Obstruction of the efflux of this filtrate into the urinary space causes bulging of the overlying cytoplasmic sheets into pseudocysts. Podocytes overlying abnormally-shaped and dilated capillary channels are generally the most seriously affected. Tuft hypertrophy, pseudocyst formation and local capillary expansion cause wide-spread apposition of podocytes to Bowman's capsule. Appositions are a prerequisite for the development of tuft adhesion. Local detachment of a podocyte from the GBM in those areas allows access of parietal cells to the GBM. In early adhesions the connection of the tuft to Bowman's capsule is established by single parietal cells which attach to both the GBM and the basement membrane of Bowman's capsule. An adhesion is considered as a nidus for segmental sclerosis; as the adhesion progresses, the related tuft regions turn into sclerosis. In the present model FGS develops exclusively in areas of tuft adhesion. PMID- 1635345 TI - Dialysis disequilibrium syndrome (DDS) in the rat: role of the "reverse urea effect". AB - DDS is characterized by neurologic deterioration and cerebral edema which occurs after hemodialysis. To investigate the pathogenesis of DDDS, we studied the effects of rapid hemodialysis on plasma and brain electrolytes, urea, and osmolality in the rat. Forty-two hours after bilateral nephrectomy, nine uremic rats were hemodialyzed for 90 minutes against dialysate without urea (model of DDS), yielding a decrease in plasma urea from 72 +/- 2 mM to 34 +/- 2 mM (P less than 0.01) and an 8% (29 mOsm/kg) decrease in plasma osmolality. This group was compared to three control groups: 11 uremic animals dialyzed against a bath with urea added so that no fall in plasma urea occurred, and 15 uremic and 12 nonuremic animals that were not dialyzed. In animals dialyzed without urea, compared to uremic non-dialyzed animals, there was a 6% increase in brain water (3.89 +/- 0.04 liter/kg dry wt vs. 3.67 +/- 0.03, P less than 0.01) and an increase in the brain to plasma (urea) ratio (1.30 +/- 0.06 vs. 0.79 +/- 0.05, P less than 0.01). Comparison of these parameters in animals dialyzed without urea versus other control groups yielded similar results. In animals dialyzed without urea, the 53% decrease in plasma urea was associated with only a 13% decrease in brain urea content. Brain content of sodium and potassium was not significantly different among groups. Retention of brain urea despite the large decrease in plasma urea was able to account for the increased brain water observed in animals dialyzed without urea.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635346 TI - Effect of insulin therapy on renal hemodynamic response to amino acids and renal hypertrophy in non-insulin-dependent diabetes. AB - Since renal hemodynamic disturbances are important in renal injury and are exacerbated by elevated plasma amino acid concentrations in insulin-dependent diabetes, we measured glomerular filtration rate (GFR) and renal plasma flow (RPF) after an overnight fast and during amino acid infusion in 12 patients with NIDDM and nine normal subjects. In the diabetic patients (plasma glucose 12.4 +/- 0.6 mmol/liter), the fasting GFR (113 +/- 6 vs. 98 +/- 7 ml/min.1.73 m2 in normal subjects, P = 0.056) and RPF (635 +/- 37 vs. 540 +/- 20 ml/min.1.73 m2 in normal subjects, P less than 0.05) were increased. After amino acid infusion, the increase in GFR (159 +/- 7 vs. 121 +/- 6 ml/min.1.73 m2 in normal subjects, P less than 0.05) and RPF (970 +/- 51 vs. 700 +/- 18 ml/min.1.73 m2 in normal subjects, P less than 0.05) were augmented. Insulin infusion for 36 hours did not change these responses. After three weeks of insulin therapy (plasma glucose 5.9 +/- 0.2 mmol/liter), the amino acid-stimulated GFR (143 +/- 5 ml/min.1.73 m2) and RPF (836 +/- 30 ml/min.1.73 m2) declined (P less than 0.05), while the fasting values remained unchanged. The right kidney volume was measured by ultrasonography and found to decrease after three weeks of insulin therapy from 188 +/- 12 to 165 +/- 9 ml/1.73 m2 (P less than 0.05). However, both values were greater than that in the normal subjects, 124 +/- 13 ml/1.73 m2 (P less than 0.01). Glomerular hyperfiltration and hyperperfusion became augmented during hyperaminoacidemia in our NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635347 TI - Measurement of glomerular filtration rate in ICU patients using 99mTc-DTPA and inulin. AB - Improved and reliable methods for assessing glomerular filtration rate (GFR) in intensive care patients are needed in light of known deficiencies using creatinine clearance. We compared simultaneous two-hour clearances of inulin (CIn), creatinine (CCr), and 99mTc-diethylenetriaminepentaacetic acid (CDTPA) in 18 medical or surgical intensive care patients (range, 49 to 92 years old) with blood urea nitrogen (BUN) levels greater than 17.9 mmol/liter (0.5 mg/ml), serum creatinine levels greater than 150 mumol/liter (0.02 mg/ml), or estimated Cockcroft clearance less than 60 ml/min. Patients had severe renal dysfunction with average GFR of 35 ml/min (range, 2 to 69 ml/min). CDTPA and CCr correlated significantly with CIn, although CDTPA tended to provide a closer approximation. Cockcroft clearance (32 +/- 4 ml/min) was grossly similar to CDTPA and CIn and correlated significantly, especially when weight was calculated using actual as opposed to ideal body weight. In a subset of 13 patients with CIn less than 30 ml/min, only CDTPA was significantly correlated with CIn. In patients in the intensive care unit, CDTPA provides a rapid, accurate, and inexpensive clinical assessment of GFR, even at very low GFRs. PMID- 1635348 TI - The pathogenesis of Alport syndrome involves type IV collagen molecules containing the alpha 3(IV) chain: evidence from anti-GBM nephritis after renal transplantation. AB - Mutations in the COL4A5 collagen gene have been implicated as the primary defect in Alport syndrome, a heritable disorder characterized by sensorineural deafness and glomerulonephritis that progresses to end-stage renal failure. In the present study, the molecular nature of the defect in Alport glomerular basement membrane (GBM) was explored using anti-GBM alloantibodies (tissue-bound and circulating) produced in three Alport patients subsequent to renal transplantation. The alloantibodies bound to the alpha 3(IV)NC1 domain of type IV collagen and not to any other basement membrane component. In tissue sections, the alloantibodies bound specifically to peripheral GBM in normal kidney and the affected renal transplant but not to that of Alport kidney. These results establish that: the alpha 3 chain in type IV collagen molecules, the Goodpasture autoantigen, is the target alloantigen in post-transplant anti-GBM nephritis in patients with Alport syndrome, and that a molecular commonality exists in the pathogenesis of anti-GBM nephritis causing loss of renal allografts in patients with Alport syndrome and renal failure in patients with Goodpasture syndrome. These findings implicate: (1) defective assembly of type IV collagen molecules containing the alpha 3(IV) chain in Alport GBM; and (2) the existence of a mechanism linking the assembly of molecules containing the alpha 3(IV) chain with those containing the alpha 5(IV) chain. PMID- 1635350 TI - 23rd Meeting of the Spanish Society of Nephrology. Madrid, Spain, October 1, 1991. Abstracts. PMID- 1635349 TI - Stimulating growth in uremic children. PMID- 1635351 TI - Society of Nephrology. Geneva, Switzerland, October 17-18, 1991. Abstracts. PMID- 1635352 TI - Immunocytochemical study of glomerular permeability to anionic, neutral and cationic albumins. AB - The renal handling of albumin of various isoelectric points (pI) was studied in mice by high resolution quantitative immunocytochemistry. Bovine serum albumin (BSA) was tagged with dinitrophenol (DNP) and cationized to pI 6.5 to 7.5 and to pI over 8.5. These tracers, including the anionic BSA-DNP (pI 4.8) were injected in the iliac vein of mice and the post-embedding protein A-gold technique was used with antibodies against DNP to localize the different tracers in renal tissue. Morphometric analysis of the labeling over the glomerular wall has demonstrated variations in its distribution according to the pI of the markers. Anionic and neutral BSA molecules were detected on the endothelial side of the basement membrane, while labeling for cationic BSA was present mainly in the laminae rarae interna and externa known to display fixed polyanionic sites. Neutral and cationic BSA-DNP reached the urinary space and were detected within the endocytotic apparatus of the proximal tubule epithelium. Neutralization of the anionic sites of the basement membrane with cationic BSA resulted in an increase in the permeability towards anionic BSA-DNP. In addition to the demonstration of glomerular permeability properties towards various probes, the present study has demonstrated that dinitrophenylated albumin represents an excellent versatile tool for the quantitative morphological investigation of glomerular permeability. PMID- 1635353 TI - Regulation of inositol transport by glucose and protein kinase C in mesangial cells. AB - Since inositol (Ins) depletion appears to be an important mechanism of cell injury in diabetic glomerulopathy, we studied Ins transport in cultured rat mesangial cells during hyperglycemia. High glucose stimulated [3H]-Ins uptake by 50 to 90% within 24 hours in a dose dependent manner. This effect was characterized by an increase in the Vmax of a Na(+)-dependent Ins transporter (10.3 +/- 0.2 vs. 16.4 +/- 0.4 pmol/mg/min, P less than 0.005). Since high glucose also induced activation of protein kinase C (PKC) in permeabilized mesangial cells, we examined the potential role of this enzyme in the stimulation of Ins transport by glucose. Both PKC inhibition with H7 and staurosporine, and down regulation of PKC by prolonged PMA (1.6 microM) treatment inhibited the stimulatory effect of glucose on Ins transport. In conclusion, high glucose stimulates Na(+)-dependent Ins transport in mesangial cells by a mechanism mediated by PKC. This process may represent an important adaptive response of mesangial cells to hyperglycemia. PMID- 1635354 TI - Blood pressure-independent effect of angiotensin inhibition on vascular lesions of chronic renal failure. AB - Previous studies in experimental models of progressive renal failure have shown that the capacity of antihypertensive drugs to protect glomeruli from sclerosis is often unpredictable from their effect on systemic blood pressure. The present study was undertaken to ascertain whether this systemic blood pressure independent structure-preserving effect of antihypertensives, particularly angiotensin II converting enzyme inhibitors (ACEI), is confined to the glomerulus or not, as well as whether this effect is mediated via angiotensin II (Ang II). The following experimental drug regimens were used in the rat model of subtotal nephrectomy (sNPX): so-called triple therapy [TRX; a combination of reserpine 5 mg/liter drinking water (DW), hydralazine 80 mg/liter DW and hydrochlorothiazide 25 mg/liter DW], or ACEI (either captopril, CPL, 600 mg/liter DW, enalapril, ENL, 400 mg/liter DW or lisinopril, LSL, 200 mg/liter DW), or a novel Ang II receptor antagonist (Ang IIR, L-158,809, 20 mg/liter DW). These dosages were identified in pilot studies to be the minimum required to control systemic blood pressure in the early phase up to 12 weeks. In addition, a separate group was treated with a higher dose of L-158,809 (80 mg/liter DW) with equipotent systemic pressor effect. Treatment was initiated eight weeks after subtotal nephrectomy following renal biopsy, and animals were sacrificed at 16 weeks. In ACEI treated rats, carotid arterial wall thickening (WT), defined as ratio of media thickening to radius of outer vessel wall, was similar to normal age-matched control (0.073 in all ACEI treated rats, vs. 0.074 in normal control) and significantly less than with TRX (ratio 0.118) or untreated sNPX (0.130). Even more remarkably, coronary arteriole WT in ACEI-treated rats averaged 0.139, a value less than one half and one third of TRX (0.298) and untreated sNPX control (0.388), respectively. Similar results were obtained for mesenteric artery WT. These findings were closely paralleled by changes of glomerular sclerosis. In untreated sNPX control rats, glomerular sclerosis increased from biopsy to autopsy specimens by an average of 458%. Although TRX dampened the degree of increase in sclerosis to on average 212%, this protective effect was far less than that achieved by ACEI. In the latter, sclerosis increased on average only 65% from biopsy to autopsy. Although all ACEIs were more effective than TRX, captopril and lisinopril groups showed greatest benefit at these doses. Ang IIR also protected renal and extrarenal structures with 34% increase of sclerosis index in low dose and WT 0.088, 0.117 and 0.112, respectively in carotid, mesenteric and coronary arteries.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1635355 TI - Permeability of dialyzer membranes to TNF alpha-inducing substances derived from water bacteria. AB - Pro-inflammatory cytokine-inducing substances derived from cultured E. coli have previously been shown to pass across low-flux regenerated cellulosic dialyzer membranes. In the present study, a sterile filtrate of Pseudomonas maltophilia grown from standard bicarbonate dialysis fluid was used to test the permeability of various dialyzer membranes (regenerated cellulose, cellulose triacetate, polyacrylonitrile, polysulfone and polyamide) to TNF alpha-inducing bacterial substances. Pyrogen-free tissue culture medium (MEM) was recirculated for 60 minutes in the dialysate compartment of a closed-loop dialysis system, then P. maltophilia filtrate was added and recirculation was continued for a further hour. Samples from the dialysate (MEM) and the blood side (containing 10% human plasma in MEM) were incubated with donor mononuclear cells (MNC) for 18 hours and TNF alpha release was measured in MNC supernatants by radioimmunoassay. Five minutes after the addition of P. maltophilia filtrate, mean TNF alpha-inducing activity in the dialysate increased from (mean +/- SEM) 0.10 +/- 0.02 to 18.2 +2- 1.5 (ng/2.5 x 10(6) MNC/18 hr). TNF alpha-inducing activity in the blood side increased with regenerated cellulose from 0.10 +/- 0.01 to 4.57 +/- 1.55 (N = 8; P less than 0.001); with cellulose triacetate from 0.20 +/- 0.05 to 0.44 +/- 0.10 (N = 5; P less than 0.05), and with polyacrylonitrile from 0.10 +/- 0.02 to 1.16 +/- 0.45 (N = 5; P less than 0.03). No increased TNF alpha-inducing activity was observed in the blood side of polysulfone (N = 5) or polyamide dialyzers (N = 5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635356 TI - Increased oxygen radical and eicosanoid formation in immune-mediated mesangial cell injury. AB - To evaluate whether monocytes/macrophages derived from glomeruli could be a source of increased eicosanoid and free oxygen radical formation in glomerular disease, monocytes/macrophage (M/M) were isolated from nephritic glomeruli and their in vitro generation of eicosanoids and superoxides were measured. Glomerular immune injury was induced by i.v. injection of a rabbit-anti-rat thymocyte antiserum (ATS). Kidneys were removed two, five, and 24 hours, and three and eight days after ATS. Adhesive glomerular macrophages were obtained by isolation of glomeruli, enzymatic digestion and incubation of the single cell suspensions in culture dishes. O2-production was evaluated by superoxide dismutase (SOD)-inhibitable reduction of ferricytochrome C; PGE2 and TxB2 release was assessed by direct RIA. Glomerular macrophage infiltration was maximal 24 hours after intravenous antibody (35.9 +/- 5.1 M/M per glomerulus). In vitro production of superoxide was significantly enhanced (P less than 0.001) five hours after ATS administration (51.6 +/- 4.4 nmol O2/10(6) MM/hr), when compared with M/M from controls (30.4 +/- 2.0 nmol O2/10(6) MM/hr). TxB2 formation of glomerular M/M was increased (P less than 0.001) two hours and five hours after ATS administration (1056 +/- 75 and 1182 +/- 112 pg TxB2/10(6) MM/hr) compared with controls (390 +/- 34 pg TxB2/10(6) MM/hr). PGE2 synthesis, however, was decreased (P less than 0.01) at five hours after ATS (629 +/- 43 pg PGE2/10(6) MM/hr) compared with controls (950 +/- 125 pg PGE2/10(6) MM/hr). Furthermore, there was release of leukotriene B4 (LTB4) in monocytes of nephritic glomeruli five hours after ATS administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635357 TI - Different mutations in the COL4A5 collagen gene in two patients with different features of Alport syndrome. AB - Alport syndrome is a hereditary renal disease in which progressive renal failure is often accompanied by sensorineural deafness and ocular abnormalities. Recently, mutations were detected in the type IV collagen alpha 5 chain gene in Alport syndrome patients. We searched for mutations in this gene in 18 unrelated patients, and in two patients abnormalities were detected. In the gene of patient BB we identified a complex deletion, which included the exons encoding the non collagenous domain and part of the collagenous region. This patient showed early onset nephritis (end-stage renal disease at 17 years) with deafness. Within a year after receiving a kidney from an unrelated donor, he developed an antiglomerular basement membrane nephritis. In patient WJ a point-mutation was detected, changing a tryptophane into a serine in the non-collagenous domain. His clinical features are milder (renal failure at 33 years, no hearing loss), and a recent renal allograft did not provoke antiglomerular basement membrane disease. These initial data suggest that differences in the extent of disruption of the non-collagenous domain may correlate with the severity and/or heterogeneity of Alport syndrome and with the development of nephritis in renal allografts. PMID- 1635358 TI - Ureteral obstruction decreases renal prepro-epidermal growth factor and Tamm Horsfall expression. AB - Northern and dot-blot analysis of polyadenylated RNAs of kidney cortical and outer medullary tissue was performed in male Sprague-Dawley rats at varying times up to 24 hours after bilateral ureteral obstruction (BUO), after 24 hours of unilateral obstruction (UUO) and at varying periods after release of BUO or UUO. Pre-proEGF (preproEGF) and Tamm-Horsfall (TH) mRNA declined by four hours of BUO to virtually undetectable levels at 24 hours of ureteral obstruction. Upon release of BUO or UUO, preproEGF and TH mRNA returned slowly toward normal but remained below control levels up to four days after release of ureteral obstruction. Urinary EGF excretion paralleled these changes in renal preproEGF mRNA. Although these changes are similar to those observed during nephrotoxic and ischemic renal failure, where the expression of the immediate early genes precedes the fall in preproEGF and TH expression, no such increase in the expression of these genes occurred after bilateral ureteral obstruction. These changes in preproEGF and TH expression could also be dissociated from uremia and high rates of DNA synthesis, suggesting that ureteral obstruction itself is a sufficient cause of the reduced expression. The increase in ureteral pressure and its functional and humoral effects may each play a role in reduced preproEGF and TH expression during ureteral obstruction. PMID- 1635360 TI - [Evaluation of the levels of selected immunoglobulins in peripheral blood of patients with recurrent anterior uveitis]. AB - The antigen of the tissular congruity HLA-B 27 appears more frequently in patients with anterior uveitis than in healthy people. The presence of this antigen in a patient may have a substantial influence on the changes seen in the peripheral blood and on the clinical picture of the condition. Coming from that assumption the authors undertook a trial of revealing the interdependence between the concentration of some immunoglobulins in the blood serum and the appearance of the above-mentioned antigen in patients with recurrent iridocyclitis. In the group of patients with the antigen of tissular congruity HLA-B 27 they found a statistically significant higher concentration of the A and G immunoglobulins than in the control group. PMID- 1635359 TI - [Effect of various light sources on visual functions in the age aspect. I. Conscious reaction time and the manual spatial visual localization]. AB - The authors present the results of investigations performed in 28 right-handed, normally seeing persons divided into 2 groups: 15 of them were in productive age and 13 in older age. The authors compared the dynamics of the behaviour of the visual functions in dependence on the age of the subjects and the stay in the glow and sodium light. No adverse influence of the sodium light on the hand localization could be detected, instead it seems that it negatively influenced the selective reaction in older productive persons in the sense of an increased number of faults. PMID- 1635361 TI - [Evaluation of the effectiveness of prostacyclin in the treatment of thrombosis of the central retinal vein using a double-blind method]. AB - The patients were divided by chance into 2 groups: the first one (15 persons) was given a natrium salt of prostacyclin (Epoprostenol Wellcome or Chinoin) in a dose of 5 mg/kg/min. intravenously by an infusion pump in 5 infusions; the control group (15 persons) received instead of prostacyclin a placebo (0.1 M glycine buffer of pH 10.5). Besides all the patients were given Doxium or Calcium dobesilate, Rutinoscorbin, Vitamin C, and Polopyrin S (Soluble Aspirin). Immediately after the completion of the treatment the authors did not find any essential differences between the examined groups. In prolonged observations however one demonstrated a significantly smaller frequency of the development of neovascularization in the eyes of persons treated by prostacyclin in comparison with the control group. PMID- 1635362 TI - [Evaluation of the effect of advanced pathological changes on the course of the treatment of patients with primary open-angle glaucoma]. AB - One hundred seventy two persons (300 eyes) with various degree of advancement of glaucomatous changes of the optic nerve were examined at the start of the treatment and after 1, 5 and 10 years. It was detected that in the eyes with a nearly full cupping of the optic disc the deterioration of the visual acuity and the advancement of field changes occurred much more frequently than in eyes with a small lesion of the nerve, as well in the eyes treated conservatively as in those treated surgically. PMID- 1635363 TI - [Personal experiences with conservative treatment of central retinal degeneration]. AB - 21 patients (40 eyes) aged 27-84 years (15 women and 6 men) were treated orally with cavinton 3 x 5 mg, sadamine++ 3 X 75 mg, cinnarizine++ 3 X 40 mg, vit. A+E 3 X 1 caps. daily. Intramuscularly++ were given vit. B1 25 mg, vit. B12 1000 micrograms, geriocaine++ 100 mg, and not in all sadamine++ 300 mg daily. Improvement of visual acuity for distance was observed in 31 eyes (77.5%) and for near vision in 17 eyes (42.5%). Within 34 eyes with visual field abnormalities in 9 the central or pericentral scotomas were observed. After medical treatment the central scotomas were diminished in 6 eyes (66.6%) and the enlargement of peripheral visual border from 10 to 30 degree in 10 eyes (40%) were observed. PMID- 1635364 TI - [Soft contact lens as an obturator in children with amblyopia]. AB - The authors present the results of application of a soft contact lens in 16 children. The lens has been used for obturation of the master-eye in the treatment of amblyopia. Particular attention was committed to the improvement of the visual acuity, retinal fixation and position of the eyes. PMID- 1635365 TI - [Immunologic response of the anterior chamber in the light of observation of the presence of bee sting]. AB - The authors present a case of a bee sting sticking for 3 days in the anterior chamber. It did not provoke any inflammatory changes except of a sector hyperemia of the iris and aqueous flare. After a surgical removal of the sting these symptoms receded. The lack of reaction to the bee poison is considered in the light of a humoral reaction and of the phenomenon of Anterior Chamber Associated Immune Deviation (ACAID) the essence of which is based on the suppression of the late type of sensitivity. PMID- 1635366 TI - [Atypical clinical picture of uveal melanoma]. AB - Presented is a case of uveal melanoma in the posterior segment of the eye. It has been accompanied by an inflammatory reaction of the anterior segment which made impossible the visual evaluation of the fundus. PMID- 1635367 TI - [Early changes in the visual system in subacute sclerosing panencephalitis]. AB - This paper presents our observations of changes in the visual system in the early period of SSPE in the group of 23 children at the age of 3 to 17 years (18 boys and 5 girls). The most frequent changes were papillary stasis (9 patients). Decreased visual acuity with no changes in the optic fundus or with chorioretinitis and simple atrophy of the optic nerve were observed in 8 children. Convergent squint, visual hallucinations and visual agnosia were additional symptoms in single cases. Changes in the visual system which appeared in early period of the disease as single clinical symptom usually create serious diagnostic problems. The greatest problem appeared when papillary stasis coexisted with other symptoms of increased intracranial pressure. Neuroradiological examinations were decisive in these cases. Diagnosis of SSPE was confirmed by further course of the disease and others additional and typical results. PMID- 1635368 TI - [Critical evaluation of the treatment of diabetic retinopathy based on personal experience]. AB - The authors present the results of analysis of the treatment of 184 patients (360 eyes) with diabetic retinopathy; it comprises as well the out-patients as the in patients divided into 4 groups in dependence on the changes and the treatment applied (laser focused photocoagulation, panretinal photocoagulation, cryopexy) the majority of patients reported to the hospital with an advanced proliferative diabetic retinopathy and this allowed only the performance of a panretinal photocoagulation and in a part of cases only cryopexy. The attention is called to the necessity of an early detection of pathological changes and of an early treatment. PMID- 1635369 TI - [Value of different serological tests in the diagnosis of various forms of active ocular toxoplasmosis]. AB - The analysis of results of indirect immunofluorescence and direct agglutination reaction in patients with various forms of ocular toxoplasmosis showed that these reactions have a limited value in diagnostics of this condition. One can define a sure diagnosis of active ocular toxoplasmosis when the titre of these reactions are higher than 512. The ELISA IgM reaction is specific for the active form of this disease. The sensitivity of this reaction amounts 43-50%. In cases of iridocyclitis the results of the serological tests were similar to those of the control group; this confirms the hypothesis that the inflammation is evoked by an allergic reaction. PMID- 1635370 TI - [Stickler's syndrome]. AB - Stickler's syndrome or congenital, progressive arthro-ophthalmopathy refers to disturbances of the connective tissue of the organism but mainly the osteoarticular and visual systems. In the visual system one discovers a congenital high myopia, pathological changes in the vitreous in the form of membranes and proliferative bands as well as retinal detachment. A metabolic defect concerning the hyaluronic acid and the collagen of the 2-d type is assumed to be the cause of this syndrome. PMID- 1635371 TI - [Radial keratotomy and the factors determining its effectiveness]. AB - The authors present a short history of the development of the idea and technique of the radial keratotomy. They discuss the individual factors as well topical (corneal curvature, intraocular pressure) as general (age, sex) and also surgical parameters influencing the final effect of operation and its stability. Presented are: the indications and contraindications for the procedure, the preoperative approach, surgical technique and the postoperative treatment. PMID- 1635372 TI - [Failures, complications and side effects of radial keratotomy]. AB - The authors present the 10-years results of radial keratotomy in the light of the world literature. The refractive and functional efficacy of this procedure as well as intraoperative and postoperative complications are discussed. The problem of the influence of the radial keratotomy on the endothelium is presented in the light of clinical and experimental investigations. The daily fluctuation of the refraction has been discussed in the aspect of diurnal variations of the intraocular pressure and the changes in corneal thickness resulting from its hydratation. The problem of binocular vision in conditions of postoperative anisometropia is also presented. PMID- 1635373 TI - [Effect of various light sources on visual functions in the age aspect. II. Visual acuity, the range of accommodation and fusion and the visual field]. AB - The authors performed examinations in 15 middle aged persons and in 13 persons of older productive age in conditions of equivalent illumination, first the glow one, then the sodium one of 600 lx value at the stand of examination. They observed the dynamics of selected visual functions as the time went by in the forenoon hours. The group of older persons tolerated worse the sodium light and in both age groups one could observe the receding of the visual near point. The authors analyze the remaining visual functions in both conditions of illumination. PMID- 1635374 TI - Regulation of hematopoietic cell function by protein tyrosine kinase-encoding oncogenes, a review. AB - Tyrosine phosphorylation of proteins by protein tyrosine kinases (PTKs) is an important mechanism in the regulation of various cellular processes such as proliferation, differentiation, and transformation. Accumulating data implicate PTKs as essential intermediates in the transduction of extracellular signals to the interior of the cell. This review summarizes the mechanism of action of PTKs from the major subclasses and the involvement of PTK-encoding oncogenes in the regulation of hematopoietic cell function. PMID- 1635376 TI - Increased serum interleukin 6 levels in patients with myelodysplastic syndromes. AB - Serum concentration of interleukin 6 (IL-6) was measured in 45 patients with myelodysplastic syndromes (MDS). A commercially available enzyme-linked immunosorbent assay (ELISA) with a sensitivity of 3 pg/ml was used. While IL-6 was undetectable in healthy volunteers, 32 of the patients with MDS showed IL-6 concentrations higher than 3 pg/ml. In MDS we found serum concentrations of IL-6 between 0 and 150 pg/ml with a median of 9 pg/ml, mean and standard deviation (SD) were 15 and 26 pg/ml respectively. In refractory anemia with excess of blasts in transformation (RAEB-t) the serum IL-6 concentrations were significantly higher than in refractory anemia (RA; p = 0.0025), in refractory anemia with excess of blasts (RAEB; p = 0.0050) and in chronic myelomonocytic leukemia (CMML; 0.0449). No significant difference was detected between RA and RAEB or between CMML and the other types of MDS, while s significant negative correlation was found between the concentrations of IL-6 and hemoglobin (p = 0.0228). PMID- 1635375 TI - Intensive sequential post-induction therapy for adults with acute myelogenous leukemia in first remission: long-term follow-up and results. AB - We designed a post-induction therapy including intensive sequential therapy with non-cross-resistant drugs in an effort to prolong disease-free survival (DFS) for adults with acute myelogenous leukemia. Forty-five patients entered this study and 33 of 35 patients entering complete remission received the post-induction therapy. With a median follow-up for survivors of 3.5 years from complete remission, the actuarial 5-year DFS was 46% +/- 19% (95% confidence interval). The five-year DFS for patients over 45 years of age was comparable to that for patients under 45 years of age (50% +/- 26% vs 47% +/- 28%). Furthermore, the actuarial 5-year DFS for patients who required two courses of induction therapy was comparable to that for patients who required only one course of induction therapy (45% +/- 29% vs 50% +/- 25%). The toxicity of post-induction therapy was tolerable and no patients died during complete remission. PMID- 1635377 TI - Binding of monoclonal anti-interleukin 2 antibody to nucleoli in acute leukemia blast cells. AB - Neutralizing anti-IL-2, anti-IL-3, and anti-IL-6 monoclonal antibodies (MAbs) were used for the immunoenzymatic detection of the respective cytokines in blast cells of 38 patients with acute myeloid (AML) and lymphoid (ALL) leukemias by the APAAP-technique. In 20/24 AML-cases (83%) blast cells showed intranuclear staining with MAb anti-IL-2 (DMS-1). In 17 cases reaction was restricted to the nucleoli, in 4 cases additional cytoplasmic staining was observed. Only 2/13 (15%) of the ALL cases showed anti-IL-2 staining. In contrast to IL-2, neither IL 3, IL-6 nor IL-2R alpha-chains were detected in any of the acute leukemias tested. The anti-IL-2 staining of nucleoli in AML cells is distinct from the cytoplasmic staining which is observed in PHA-activated normal lymphocytes and in a minority of AML cells. PMID- 1635378 TI - High constitutive expression of heat shock protein 90 alpha in human acute leukemia cells. AB - The constitutive expression of the genes for four heat shock proteins (hsps) was studied in leukemia cell lines, cells obtained from patients with acute leukemia, and normal blood cells by means of Northern-blot analysis. Western-blot analysis with hsp90 antibody showed that the leukemia cells contained larger amounts of hsp90 than the normal peripheral mononuclear cells. The expression of the hsp90 alpha gene was enhanced in the leukemia cell lines and the acute leukemia cells from patients as compared with the normal blood cells. In contrast, the expression of the hsp90 beta gene could hardly be recognized in either the acute leukemia cells or the normal blood cells. An increased expression of hsp70 gene was observed in only one patient. The expression of the hsp27 gene was enhanced in one-half the patients with common acute lymphoblastic leukemia. Thus, exclusively the hsp90 alpha gene was expressed highly in the leukemia cells, indicating its association with cellular proliferation. PMID- 1635379 TI - The effect of high-dose methylprednisolone treatment on GM-CSF level in children with acute leukemia: a pilot study. AB - High-dose methylprednisolone therapy (HDMP) induces acceleration of leukocyte recovery in acute lymphoblastic leukemia (ALL) and the differentiation of myeloblasts to mature granulocytes in acute myeloblastic leukemia (AML). These effects of corticosteroids have been shown to be due to the enhanced colony stimulating activity (CSA) and responses to corticosteroids in some patients with aplastic anemia and myelodysplastic syndromes (MDS) have been related to increased CSA activity. We measured the serum (granulocyte-macrophage colony stimulating factor (GM-CSF) levels by a sandwich linked immunoabsorbent assay (ELISA) in patients with ALL and AML at presentation and following high-dose methylprednisolone (HDMP) therapy. Serum GM-CSF levels at presentation in the ten cases studied ranged between 160 and 700 pg/ml (mean 418.5 +/- 252.5). One week following HDMP therapy GM-CSF levels increased to between 260 and 950 pg/ml (733.5 +/- 203.2). Four weeks after therapy the GM-CSF levels increased to between 470 and 1350 pg/ml (911 +/- 278.7). GM-CSF levels were markedly elevated one week after HDMP in the patients with ALL, suggesting that in addition to the lymphotoxic effects on leukemic blasts, the acceleration in neutrophil recovery may be due to release of GM-CSF induced by HDMP and its effects on myeloid progenitors. PMID- 1635380 TI - Is cigarette smoking a risk factor for non-Hodgkin's lymphoma or multiple myeloma? Results from the Lutheran Brotherhood Cohort Study. AB - Among 17,633 U.S. white male insurance policy holders whose use of tobacco was characterized in a 1966 self-administered questionnaire, there were 49 deaths from non-Hodgkin's lymphoma (NHL) and 21 from multiple myeloma (MM) during a 20 year follow-up. Men who had ever smoked cigarettes had an elevated mortality from NHL (RR = 2.1; CI = 0.9-4.9), with risk almost four-fold greater among the heaviest smokers (RR = 3.8; CI = 1.4-10.1) compared with those who used no tobacco. In contrast, risk of MM was only slightly elevated among those who had ever smoked cigarettes (RR = 1.3; CI = 0.4-3.9) and without evidence of a dose response trend. Since this is the first cohort study suggesting a link between cigarette smoking and NHL and findings from case-control studies have been inconsistent, additional clarification should be sought from larger incidence based cohort investigations. PMID- 1635381 TI - The cytotoxic effects of 5-OH-1,4-naphthoquinone and 5,8-diOH-1,4-naphthoquinone on doxorubicin-resistant human leukemia cells (HL-60). AB - The effect of 5-OH-1,4-naphthoquinone and 5,8-diOH-1,4-naphthoquinone, two quinones highly reactive with oxygen, was studied on HL-60 and HL-60R cells. The multidrug resistance developed by the doxorubicin-resistant HL-60 cell line did not prevent the cytotoxic effect of these compounds, at clinically relevant concentrations. An increase in cellular defenses against oxygen radicals seemed to be one of the features developed by HL-60R, since the homogenate from this cell line had only 65% of the ability of the original cell line to form oxygen radicals during doxorubicin reduction. This result may be explained in part by the slight increase in superoxide dismutase and DT-diaphorase enzymatic activities. PMID- 1635384 TI - Effects of a fibroblast-derived inhibitor on the growth of normal marrow and leukemic clonogenic cells. AB - Blood cells develop in the bone marrow, controlled by a network of regulatory factors, some of which originate in the stroma. Previously, we found that most fibroblastoid (FB) cells growing in primary cultures of rat marrow bear surface antigens different from those found on FB of certain other tissues. As determined by two monoclonal antibodies ("ST3" and "ST4"), the "marrow type" is ST3+/ST4- and releases predominantly a colony-stimulating activity (CSA) into its culture media (CM), whereas the "peripheral type" (e.g. lung) is predominantly ST3-/ST4+ and produces inhibitory activity in excess of CSA. The studies described here show that this inhibitor also is active on rat leukemic myeloblasts (the BNML cell line), but not on eight other cell lines derived from rat tumors of various origins or on the human-derived leukemic cell lines tested. It was produced without exogenous stimulation, was labile to heat and acid, was not neutralized by antisera to transforming growth factor-beta, beta-interferon, or ferritin, and had an apparent mol wt in the range of 100-120 kD (peak of activity by gel filtration). From the results obtained at this time, we are not able to ascribe this fibroblast-derived activity to any known inhibitor molecule. PMID- 1635383 TI - Intranuclear concentration measurements of doxorubicin in living leucocytes from patients treated for a lympho-proliferative disorder. AB - The accumulation of doxorubicin (DOX) in white blood cells of treated patients has been studied by quantitative microspectrofluorometry. From blood samples of treated patients, leucocyte subpopulations were separated by the gradient method. Emission fluorescence spectra from a microvolume of a single living cell nucleus were analysed in terms of spectral shape and fluorescence yield between free and DNA-bound doxorubicin. With this non-destructive analysis technique, intranuclear doxorubicin concentrations were determined within +/- 10%. Doxorubicin concentrations were measured in patients treated with bolus injection. After an accumulation of DOX in leucocytes during the first 30 min, intranuclear doxorubicin concentration did not vary significantly for 24 h, whereas its concentration in plasma decreased. Despite large differences between patients, monocytes accumulated significantly more doxorubicin than granulocytes or lymphocytes did. PMID- 1635382 TI - Flow cytochemical analysis of peripheral lymphocytes in chronic B-lymphocytic leukemia. Prognostic role of the blast count determined by the H*1 system and its correlation with morphologic features. AB - Peripheral blood samples from 148 previously untreated patients with chronic B lymphocytic leukemia (B-CLL) were analyzed with the Technicon H*1 flow cytometer. The absolute number and the percentage values of both LUCs (large unstained cells) and blasts were correlated with survival, as well as with well-known prognostic factors including morphological subtypes of lymphoid cells. Results showed that patients at the most advanced clinical stages (Rai: III and IV; Binet: C) had the highest percentage and count of both LUCs and blasts. Furthermore, the proportion of LUC positively correlated with the following prognostic factors: peripheral lymphocytosis (greater than 50 x 10(9)/l); marked splenomegaly (greater than 10 cm UCM); % of circulating prolymphocytes, % immunoblasts, and % LGL. Our data analysis further revealed that chemotherapy produced a greater reduction of both the LUCs and of the blast count than of that of small lymphocytes. An increase in LUC count was found to coincide with deterioration of clinical status (progressive changes in the clinical stages, occurrence of prolymphocytoid transformation). A rapid increase in blast count was found to occur in concomitance with the development of Richter's syndrome, and correlated positively with the number of peripheral immunoblasts determined by light microscopy. Moreover, a blast percentage higher than 7% had the strongest predictive relation to survival rate when compared with other hematological parameters (lymphocytosis greater than 50 x 10(9)/l, % of LUCs greater than 12%, LUC to lymphocyte ratio greater than 16%, LUCs count greater than 2.2 x 10(9)/l). In the light of these findings, it may be suggested that the presence both of larger proportions of LUCs and of blasts measured with the flow cytometry may be considered unfavorable prognostic factors in B-CLL. However, based on morphological and multivariate statistical analyses, the blast count proved to be the most important prognostic parameter determined by the H*1 system in B-CLL. PMID- 1635385 TI - A patient with monosomy 7 and polyuria. AB - Diabetes insipidus (DI) is a rare complication of leukaemia. An association between monosomy 7 and DI in leukaemias has been proposed. We present a case of Ph1-positive CML who developed polyuria at the time of lymphoid blast transformation associated with loss of chromosome 7. Biochemical results were not diagnostic of DI and a therapeutic trial of DDAVP was unsuccessful. Post-mortem showed a peripituitary and renal leukaemic infiltrate and although DI is a possibility, the cause of his polyuria remains unresolved. PMID- 1635386 TI - 5th International Workshop on Chronic Lymphocytic Leukemia. AB - In the past few years important advances have been made in our understanding of the biology and natural history of CLL; also, new strategies and agents offer promise in the treatment of this form of leukemia. Now, patients can be treated on a more rationale basis and with real prospects for a sustained control of their disease, and improved quality of life. Hopefully, progresses in CLL will continue to accumulate in the coming years. PMID- 1635387 TI - Enhanced NK activity during blast crisis in chronic myelogenous leukemia (CML) PMID- 1635388 TI - Macrophage colony-stimulating factor production in leukemic cell lines compared to normal T cells. PMID- 1635390 TI - Isochromosome 11q in acute erythroblastic leukemia. PMID- 1635389 TI - Can dipyridamole or verapamil slow regrowth of leukaemia cells? PMID- 1635391 TI - [Seroprevalence of human immunodeficiency virus infection at an emergency service of an urban area]. AB - BACKGROUND: Objectification of the seroprevalence of infection by the human immunodeficiency virus (HIV) among patients consulting in a hospital emergency ward of an urban area is presented. Detection of unknown carriers of HIV is also reported as well as an evaluation of the reasons for consultation by these patients in emergency wards. METHODS: A prospective study was carried out in the emergency ward of internal medicine with the random selection of 500 patients. In each case the following were evaluated: previous epidemiology of HIV, reason for consultation and clinical suspicion of HIV infection. The determination of HIV antibodies was carried out in all patients by ELISA with a further ELISA and Western blot being performed for seropositivity. RESULTS: 8.4% of the patients included were previously known carriers of HIV. In addition, 1.1% presented positive serology vs previously unknown HIV. The most frequent reason for consultation was a febrile syndrome followed by digestive and respiratory symptomatology. CONCLUSIONS: There is a high seroprevalence of HIV carriers among patients consulting in emergency wards with an unnegligible percentage of unknown carriers. The profile of previously unknown HIV carriers is that of male between 25-35 years of age consulting for a febrile syndrome of no apparent focus who pertains or has previously pertained to a risk group. PMID- 1635392 TI - [Nephropathy in human immunodeficiency virus infection]. AB - BACKGROUND: Patients with the human immunodeficiency virus (HIV) infection may present different types of nephropathy with focal segmentary glomerulosclerosis (FSGS) being the most specific lesion associated to HIV (HIVN). The prevalence of this entity varies between 1 to 23%. These differences have been attributed to ethnic factors and/or intravenous drug addiction (IVDA). The renal alterations presented in these patients with HIV infection were analyzed. METHODS: Two groups of patients were studied: Group I with 300 consecutive patients with advanced HIV infection (complex related with AIDS) treated with zidovudine without initial kidney infection followed for a mean of 19 +/- 11 months (99% caucasian, 65% IVDA, 66% AIDS); and group II with 11 patients with HIV infection remitted for kidney involvement (4 on hemodialysis). RESULTS: Group I: 26 cases (9%) presented acute reversible kidney failure (12 prerenal, 9 nephrotoxicity and 5 mixed). No patient presented HIVN criteria. Group II: one black patient developed HIVN and had no known risk factors. The remaining patients presented glomerular changes different from those of HIVN. CONCLUSIONS: The scarce prevalence of human immunodeficiency virus nephropathy in the present series is of note despite the high number of intravenous drug addicts included suggesting that ethnic factors determine the differences observed in different series. The most frequent kidney disturbances seen are those related with infectious complications associated to the acquired immunodeficiency syndrome and the treatment of the same. PMID- 1635393 TI - [Prevalence of human immunodeficiency virus infection, hepatitis B virus and syphilis in full term pregnancy]. AB - BACKGROUND: The estimation of the frequency of infection by HIV, hepatitis B virus and syphilis in unselected populations of full-term pregnancy is useful for epidemiologic surveillance of these diseases and for decision marking in prenatal detection. METHODS: A transversal study of 3,193 women who gave birth in the Hospital General de Elche between March 1989 and February 1990 was carried out. A blind survey was developed to avoid ethic problems and bias derived from the undertaking of HIV test without patient consent. RESULTS: The prevalence of HIV was 0.5/1,000 women (CI 95%, 0-1.5); HBV 8.9/1,000 (CI 95%, 4.6-13.2) and syphilis 1.5/1,000 (CI 95%, 0.9-2.1). CONCLUSIONS: The diffusion of the AIDS epidemic in Spain to the general population does not at present seems important although studies should be performed in the future to monitor the trend. The prevalence of syphilis in Spain is low in this study in comparison with the results of other Spanish studies which may be explained by greater quality of care in to pregnancy. The prevalence of HBV suggests the need for detection and vaccination of newborns. PMID- 1635395 TI - [Aids: where we are and where we are heading]. PMID- 1635394 TI - [Multicenter study of the prevalence of type 2 human immunodeficiency virus infection in Spain (1990)]. AB - BACKGROUND: HIV-2 is a new retrovirus which may produce AIDS and has been mainly described in individuals from West Africa. More than 400 cases have been reported in France and Portugal while in Spain very few cases of HIV-2 infection have been reported with few studies having been made concerning the prevalence of the disease. This multicentric study analyzes the prevalence of HIV-2 infection in subjects of different risk groups in Spain and evaluates the diagnostic efficacy of different methodologies. METHODS: The presence of HIV-2 antibodies was analyzed in 902 serum samples of high risk individuals collected in 1990 from: 386 drug addicts, 246 not drug addict prostitutes, 184 West Africans and 86 homo/bisexual individuals. These samples were from Barcelona, Sevilla, and Malaga. The detection of antibodies was carried out by enzymatic immunoanalysis (EIA), Western blot (WB) and an enzymoimmuno-dot (EID) designed with synthetic peptides. RESULTS: Positive serology only for HIV-2 was detected in 7 samples from African immigrants. Two drug addicts presented double reactivity HIV-1/HIV-2 in all the tests suggesting double infection. No prostitutes or homo/bisexual males were identified with positive serology for HIV-2. Cross-reactivity between HIV-1 and HIV-2 was more frequently detected in WB than in EID. Greater discordance was found in the results obtained by EIA, WB, and EID in the West Africans than in the analysis of the samples of native subjects. CONCLUSIONS: This study demonstrates that, for the time being, HIV-2 infection in Spain is rare although from among immigrants from endemic areas subjects with behavior to risk of transmission to the autochthonous population have been identified. The use of techniques designed with synthetic peptides may be of use to discriminate HIV-1 and HIV-2 infection in positive samples by enzymatic immunoanalysis (EIA) and Western blot which use a viral lysate as antigenic material. PMID- 1635396 TI - [Human immunodeficiency virus infection in seronegative subjects: myth or reality?]. PMID- 1635397 TI - [Cell cultures: usefulness in biomedical research]. PMID- 1635399 TI - [Supraclavicular silicoanthracotic adenopathy]. PMID- 1635398 TI - [Cavitated pulmonary mass in a 19-year-old male]. PMID- 1635400 TI - [Cerebello-extrapyramidal syndrome as the only manifestation of poisoning with tricyclic antidepressives]. PMID- 1635401 TI - [A proposal of a deontologic decalogue]. PMID- 1635402 TI - [Regional differences in amiodarone consumption]. PMID- 1635403 TI - [Role of conservative surgery in the multidisciplinary treatment of Ewing's sarcoma in childhood]. AB - BACKGROUND: In order to cure Ewing's sarcoma it is necessary to have an approach which considers the radical local control on the sites of macroscopic disease, along with the systemic control of micrometastases. On the present study the experience of the authors in analyzed, remarking the role of cytoreduction surgery on curability. METHODS: From January 1982 to August 1991, 24 patients with the mean age 13 years, 14 boys and 10 girls, previously untreated and with a pathology proven diagnosis have been treated by the authors. The treatment protocol included: alternating chemotherapy with cyclophosphamide, adriamycin, methotrexate, bleomycin, actinomycin D and vincristine; administered simultaneously with preoperative external radiation with a volume that completely included the affected bone and surrounding soft tissues for a total dose of 45 Gy/4.5 weeks. After a resting period of 4 weeks, resection of the involved bone and adjacent healthy bone was performed, followed by a single dose of 10-15 Gy of intraoperative radiotherapy to the tumor bed. Subsequently a custom prostheses or allograft was implanted. RESULTS: Twenty patients had localized disease and 4 had metastatic disease at diagnosis. In 16 cases the tumor was in extremities, 5 axial, and 3 extraskeletical. In 15 patients surgery with limb sparing techniques was performed, 8 had en block resection and one amputation (calcaneous location). At the time of this report 21 patient are alive (87%). Four had disease progression, of this 3 had died (12%). The actuarial disease free survival rate is 80% +/- 9% with a follow-up of 104 months, being the mean survival time of 85.5 months. CONCLUSIONS: The cytoreduction surgery included into a multidisciplinary approach permits to achieve a high rate of cure in Ewing's sarcoma. The toxicity of the program can be considered acceptable. PMID- 1635404 TI - [Influence of chronic renal failure and of its treatment on serum erythropoietin]. AB - BACKGROUND: In order to know the influence of dialysis treatment in erythropoietin production, serum erythropoietin (Ep) has been studied in patients with anemia due to chronic renal failure (CRF). METHODS: Thirty six of them in hemodialysis (HD), 10 in continuous ambulatory peritoneal dialysis (CAPD) and 18 in predialysis stage (PD) and their results were compared to two control groups, including 72 healthy controls (HC) and the second one 89 iron deficiency anemia patients (ID). RESULTS: Patients had lower Hb and Ep levels than the other groups. Although Ep was higher in CAPD and PD. Ep levels were similar to HC values, and lower than ID levels. It could be demonstrated any correlation between Hb and Ep in CRF patients, however a negative exponential correlation was demonstrated in ID patients between Hb and Ep (r = -0.83; p less than 0.00001). In summary, Ep is higher in CAPD and in PD than in HD, but the levels are lower than they should be expected. CONCLUSIONS: These data confirm an Ep production failure in most of IRC patients and it seems likely that Ep treatment could be effective to treat the anemia of CRF. PMID- 1635405 TI - [Primary cerebral lymphoma in 10 patients with AIDS. Comparative clinico radiologic study with cerebral toxoplasmosis, cerebral tuberculoma and primary cerebral lymphoma in non-immunodepressed patients]. AB - BACKGROUND: Primary central nervous system lymphoma (PCNSL) is the second cause of cerebral masses in patients with the acquired immunodeficiency syndrome (AIDS). The present study evaluated the possible presence of clinical or radiologic signs permitting differentiation of AIDS patients and PCNSL from those with cerebral masses of other etiologies. METHODS: Clinical history and cranial computerized tomography (CT) of patients with PCNSL and AIDS from the Hospital Clinic i Provincial in Barcelona were reviewed. Results were compared with those of patients with PCNSL without evidence of immunosuppression and with those with AIDS and cerebral toxoplasmosis or tuberculoma diagnosed during the same period. RESULTS: Of 685 patients with AIDS, 10 were identified with PCNSL. The clinical picture was not different to that observed in patients with AIDS and cerebral toxoplasmosis or tuberculomas. In contrast to PCNSL in non immunodepressed patients, the cerebral CT in patients with PCNSL and AIDS demonstrated hyperdense lesions in only 44% and contrast enhancement was not homogeneous in any case. These characteristics were similar to those observed in the CT of patients with cerebral toxoplasmosis or tuberculoma with the exception that only 8% of the lesions by toxoplasmosis were spontaneously hyperdense. CONCLUSIONS: The clinical radiological data of primary central nervous system lymphoma in patients with the acquired immunodeficiency syndrome are similar to those observed in other etiologies. However, the presence of a sole spontaneously hyperdense region in cranial computerized tomography is more suggestive of primary central nervous system lymphoma than cerebral toxoplasmosis. PMID- 1635407 TI - [Molecular epidemiology]. PMID- 1635406 TI - [Familial study for the early diagnosis of insulin-dependent diabetes mellitus]. AB - BACKGROUND: Diabetes is more frequently found than expected in families of first grade with children with diabetes type I. METHODS: With the aim of identifying the potential candidates prone to develop diabetes type I, genetic and metabolic analysis was carried out on the members of 11 families with a diabetic type I child. They were distributed into three groups: 11 diabetic patients (IDDM); 22 progenitors and 13 unaffected siblings. The HLA haplotype was determined, the spectrum of autoantibodies and the intravenous glucose tolerance test (IVTT) were performed. RESULTS: In two progenitors postprandial glycemia values corresponding to intolerance to carbon hydrates were obtained. Moreover, in one the IVTT was found to be low in the normal values. Of a total of 12 non diabetic descendents studied, 4 shared identical HLA haplotypes as the diabetic, 5 were haploidentical and 3 unidentical. The DR 3 antigen was detected in 90% of the diabetics; in 68% of the progenitor group and in 50% of the non diabetic descendents. Sixty-two percent of the children inherited the DR 4 antigen of the father (p less than 0.05), while 37% do so from the mother. Of the siblings with a haplotype identical to that of the diabetic, 2 were also ICA positive; asymptomatic at the moment of the study but in one the diabetes type I became manifest after 2 years of evolution. CONCLUSIONS: Subjects at high risk of becoming type I diabetics may be identified at a preclinical phase by means of HLA typing and the detection of immunologic and metabolic markers associated with the disease. PMID- 1635408 TI - [Contribution of continuous ambulatory monitoring of arterial pressure to the diagnosis and treatment of arterial hypertension]. PMID- 1635409 TI - [Pulmonary infection caused by Rhodococcus equi in a renal transplant recipient]. AB - Rhodococcus equi is a primarily pathogen in animals and it has only rarely been seen in immunocompromised humans. We describe our experience with an HIV-negative patient with a functioning renal graft under cyclosporin-azathioprine-prednisone therapy. The patient died after a two months recurrent multifocal pneumonia. The cultures from sputum and blood were negatives but R. equi was isolated from lungs in the necropsy. Most of the 41 cases we had found in the literature had AIDS or HIV infection. Six cases had a kidney graft under azathioprine-prednisone therapy. Rhodococcus equi infection may be missed in some instances due to incomplete or improper identification of the organism, that grows well in aerobic media but is usually regarded as a component of normal flora or as a contaminant. The ability of R. equi to persist in and eventually to destroy macrophages is the basis of its pathogenicity. It also explains the clinical resistance to antibiotics without intracellular activity. Rhodococcus equi infection must be suspected in immunocompromised patients with recurrent pneumonia. Correct identification and combined therapy with lipophilic antibiotics that penetrate the macrophages are necessary to prevent the high mortality of this infection. PMID- 1635410 TI - [Chronic myeloid leukemia after chemotherapy treatment for non-Hodgkin's lymphoma]. AB - A 52 year old male presenting chronic myeloid leukemia (CML) Philadelphia chromosome positive (Ph) four years after the diagnosis of a non Hodgkin's lymphoma is described. The patient had received high total doses of alkylating drugs (cyclophosphamide and chlorambucil) as part of chemotherapy treatment for a diffuse mixed lymphoma. At four years of diagnosis of the lymphoma the appearance of hepatosplenomegaly, leukocytosis with myeloma and basophilia and thrombocytosis were observed. These alterations augmented progressively until a cytogenetic study of the bone marrow two years late established the diagnosis of CML upon demonstrating the presence of the Ph chromosome with no other karyotypic anomalies being observed. The explorations carried out at that time confirmed that the lymphoma continued to be in remission. The CML initially responded to treatment with busulphan. However, following a year and a half the disease evolved to a phase of acceleration and the patient died a few weeks later due to pneumonia with no signs indicative of lymphoma activity having been detected since the diagnosis of the CML. PMID- 1635411 TI - [Direct methods for the detection of the human immunodeficiency virus]. PMID- 1635412 TI - [The day that I did not kill Mikado]. PMID- 1635413 TI - [Severity indexes and prognosis in intensive care. Their application in diabetic hyperosmolar coma]. PMID- 1635414 TI - [Prognostic factors in bladder carcinoma]. PMID- 1635415 TI - [Anatomopathologic diagnosis of Alzheimer's disease]. PMID- 1635416 TI - [Spontaneous bacterial peritonitis and pneumoperitoneum]. PMID- 1635417 TI - [Miliary tuberculosis secondary to intravesical instillation of Calmette-Guerin bacilli]. PMID- 1635418 TI - Interaction of antidepressants with 4-aminopyridine. AB - Systemic administration of 4-Aminopyridine at a dose of 4 mg/kg (4-AP) induces hypothermia in mice. Scopolamine (ED50 = 0.26 mg/kg) and two tricyclic antidepressants, desipramine (ED50 = 1.82 mg/kg) and IM/P/3/4 (ED50 = 8.95 mg/kg) completely antagonize 4-AP-induced hypothermia, whereas minaprine (0.1-0.25 mg/kg), a non-tricyclic antidepressant, reverts only 45% of the maximal effect of 4-AP. Oxotremorine at a dose of 0.05 mg/kg (OXO) induces a hypothermic effect comparable to that of 4-AP. Scopolamine (ED50 = 0.011 mg/kg) completely reverts OXO-induced hypothermia whereas desipramine and IM/P/3/4 never produce more than 60% of antagonism over a wide range of doses. Minaprine does not affect OXO induced hypothermia. These results suggest that the interaction of antidepressants with cholinergic function occurs mainly at the pre-synaptic level. PMID- 1635419 TI - Effects of (S)-alpha -fluoromethylhistidine and metoprine on locomotor activity and brain histamine content in mice. AB - We examined the effects of (S)-alpha -fluoromethylhistidine (FMH), an inhibitor of histidine decarboxylase, and metoprine, an inhibitor of histamine N methyltransferase, on the locomotor activity and the brain histamine content of ICR mice. The brain histamine content was decreased by FMH (12.5 or 50 mg/kg, i.p.) and increased by metoprine (4 mg/kg, i.p.). Under these conditions, the locomotor activity and the number of rearing were significantly decreased and increased by FMH and metoprine, respectively. The higher the brain histamine content, the greater the locomotor activity and vice versa. In a previous paper [Sakai et al., Life Sciences, 48, 2397-2404 (1991)], we showed that thioperamide, a histamine H3 antagonist, which enhances the release of histamine from histaminergic neurons, in doses of 12.5 and 25 mg/kg, i.p. increases the locomotor activity, whereas it decreases the brain histamine content. Taken together, these results support the hypothesis that central histaminergic neurons may be involved in the control of state of locomotion and rearing. PMID- 1635420 TI - Rapid and simple gas chromatographic measurement of lactic acid in red blood cells, plasma, and tumor cells after hyperthermia. AB - The content of lactic acid in red blood cells, plasma, and Ehrlich ascites tumor cells were measured by a gas-liquid chromatography using a column with a terephtalic acid support coated with polyethylene glycol-6000. The lactic acid contents were directly determined in aqueous samples, because they were converted to a volatile derivative in the column. The method was rapid and simple, compared with previous methods which need time-consuming conversion of lactic acid to volatile derivatives. Our measurements showed the increase in the contents of intra- and extracellular lactic acid after hyperthermia. PMID- 1635421 TI - A new test for measuring diapause in the pink bollworm Pectinophora gossypiella Sunders. AB - An ELISA test was developed to assay for the presence of a protein, pectinophorin, that is expressed only in diapausing last instar larvae of the pink bollworm, Pectinophora gossypiella Saunders. Use of the test provides a good estimation of the percent of diapause larvae in populations of pink bollworm in cotton fields in California and Arizona. All plow down dates are chosen before the majority of larvae enter diapause so as to eliminate as many overwintering survivors as possible. These dates may now be determined more precisely for any given field by use of the new ELISA procedure. PMID- 1635423 TI - Estimation of unbound concentrations of morphine from microdialysate concentrations by use of nonlinear regression analysis in vivo and in vitro during steady state conditions. AB - The unbound concentration of morphine in striatum of rats was estimated during a constant rate infusion of morphine 14 mumol/h*kg, by use of the microdialysis technique and nonlinear regression analysis. The concentrations in plasma of morphine and its metabolite, morphine-3-glucuronide, were 4.2 +/- 1.4 microM and 7.7 +/- 4.0 microM, respectively, during the constant rate infusion. The corresponding estimated unbound concentrations of morphine in striatum varied between 0.06 and 0.11 microM. No morphine-3-glucuronide was detected in the brain dialysates. The unbound concentration in striatum was lower than expected based on unbound plasma concentrations and could be an indication of active transport from the brain. Five different equations were tested to find the best empirical description of the relationship between microdialysate concentration and perfusion rate by nonlinear regression analysis. The equations were validated by a serum in vitro study, where three unbound concentrations of morphine estimated from microdialyis were compared to estimates obtained from equilibrium dialysis. The precision of the parameter estimates obtained from the five equations was tested by Monte Carlo simulations. One of the equations (Eq. 4) was selected in preference to the others, because of the good agreement with the estimated unbound concentration obtained by equilibrium dialysis in vitro, and good precision of the parameter estimates. The method described in this paper is valuable when estimating the unbound concentration of drug from microdialysate concentrations during steady state conditions. Furthermore, the method is easily accessible when working in the pharmacokinetic and pharmacodynamic field. PMID- 1635422 TI - Protein kinase C activity during sphinganine potentiation of retinoic acid induced differentiation in a human leukemia cell line (HL-60). AB - The differentiation of HL-60 promyelocytic cells toward mature granulocytic cells induced by retinoic acid (RA) was accompanied by a decrease in protein kinase C (PKC) activity. The enhancement of RA-induced differentiation and the potentiation of the decrease of PKC activity by sphinganine (SP) seemed to correlate with each other. Kinetically, PKC activity during RA-induced differentiation without SP decreased to its lowest (75% of the control) after 48h; about 50% of the reduction was observed at 24h. In the presence of SP, PKC activity decreased more rapidly to its lowest (60% of the control) within 24h of incubation of RA. SP, added 24h before or concomitantly with the addition of RA, could potentiate the RA-induced differentiation and the reduction of PKC activity. Our results indicate that the effect of SP and the role of PKC during RA-induced differentiation may be critical at the early stages of induction of differentiation (within 24h of RA exposure). PMID- 1635424 TI - Powerless? Not if we don't want to be. PMID- 1635425 TI - UNICEF launches the Baby-Friendly Hospital Initiative. PMID- 1635426 TI - Clarifying HIB schedules. PMID- 1635427 TI - ICEA position statement on maternal substance abuse. PMID- 1635428 TI - Don't forget to play! PMID- 1635429 TI - Neonatal and pediatric PEG tubes. PMID- 1635430 TI - Nursing alert: vertical transmission of HIV and HBV. PMID- 1635431 TI - Parental prerogatives: Newmark v. Williams. PMID- 1635432 TI - Maternal drug abuse and its effects on young children. PMID- 1635433 TI - Bridging the cultural gap with Southeast Asians. PMID- 1635434 TI - Alcohol and other drug education videos. PMID- 1635435 TI - Biases in meta-analysis and how to compensate. PMID- 1635436 TI - Thyrotoxic periodic paralysis in the United States. Report of 7 cases and review of the literature. AB - Although hypokalemic periodic paralysis is a common complication of hyperthyroidism among Asian populations, it is an uncommon problem in the United States. The recent experience in an American medical center with 7 patients with thyrotoxic periodic paralysis (TPP) is reviewed. Compared to most descriptions of this disorder, which tend to reflect the international experience with this disease, patients with TPP in the United States reflect the ethnic makeup of the local population: the predisposition of patients of Asian origin is very evident, but whites are more frequently affected than most previous reports have recognized. Hispanics and American Indians also appear to be at increased risk, and blacks have also been affected. Except for the fact that hyperthyroidism is an absolute requirement for expression of the disease, TPP is identical to familial periodic paralysis (FPP) in its clinical presentation. TPP affects predominantly males (to an even greater degree than FPP), is rarely associated with a positive family history, and has a later onset of presentation than FPP (reflecting the need for hyperthyroidism to occur before the disorder can be expressed). Graves disease is the most common cause of hyperthyroidism in affected patients, but any cause of thyrotoxicosis (including administration of excessive amounts of exogenous thyroid hormone) can trigger attacks of TPP in susceptible subjects. Clinical features of thyroid disease may be very subtle or virtually nonexistent; as a result, thyroid function tests should be routinely monitored in patients with features of hypokalemic paralysis. The pathophysiology of the disorder is not well understood. Definitive treatment of hyperthyroidism leads to cessation of periodic hypokalemic paralysis, but symptoms can return with recurrence of the hyperthyroid condition. Potassium administration during an acute attack will shorten the duration of the episode, and treatment with propranolol, potassium supplementation, or spironolactone may prevent attacks in some patients. PMID- 1635437 TI - Gastrointestinal manifestations of epidermolysis bullosa. A study of 101 patients. AB - One hundred one patients with EB were evaluated by a combination of prospective and retrospective review, and analyzed regarding the nature, incidence, and prevalence of their gastrointestinal (GI) manifestations. Involvement of the GI tract is a well-known extracutaneous manifestation of dystrophic EB, but it also occurred in more than one-half and one-third, respectively, of those with junctional and simplex EB. Most of the serious consequences, such as esophageal strictures and microstomia, occurred in recessive dystrophic EB but were also seen, although infrequently, in the junctional and simplex forms. The majority of patients with dysphagia had an esophageal stricture, and the cervical esophagus was the most common location. The onset of dysphagia generally occurred in the first decade of life, in patients much younger than previously recognized. Diagnostic endoscopy did not reveal lesions which could not have been detected radiographically. Lower GI complaints were common, especially constipation and perianal blistering, and affected all types of EB. These complaints contributed substantially to management problems but they did not correlate with colonic pathology and appeared to reflect anal or perianal disease. PMID- 1635438 TI - Nocardiosis in patients with human immunodeficiency virus infection. Report of 2 cases and review of the literature. AB - Nocardia infection is a rarely reported opportunistic infection in HIV-infected patients. Nocardiosis typically occurs in HIV-infected patients with advanced immunodeficiency (89% of cases), often as the initial serious opportunistic infection (42% of cases). In most HIV-infected patients, nocardia infection is disseminated at the time of diagnosis and is characterized by an indolent course that may be difficult to differentiate from other systemic infections. Invasive procedures to obtain tissue of fluid for culture are frequently necessary to make the diagnosis, although a Gram or modified acid-fast stain of sputum or other infected material may suggest the etiologic agent. Although trimethoprim sulfamethoxazole is the most commonly used initial therapy, it was discontinued in 50% of cases because of adverse reactions. Even though the optimal treatment has not been defined, nocardiosis in HIV-infected patients can be treated successfully with or without sulfa-containing antimicrobial regimens, along with surgical drainage when necessary. Recurrence is noted after short duration of treatment, and consideration should be given to lifelong maintenance therapy. PMID- 1635439 TI - Wilson disease. AB - Wilson disease is an inherited disorder of copper metabolism. Progress has been made in establishing the location of the gene on the long arm of chromosome 13, and in finding nearby probes that can be used to identify affected sibs of newly diagnosed patients. However, the gene has not been cloned, and the molecular nature of the defect remains unknown. The cause of the disease is a failure to excrete unneeded and excessive copper in the bile for loss in the stool. This may be due to a failure to excrete copper packaged in ceruloplasmin into the bile. Clinically, patients usually present during the second to fourth decades of life with liver, neurologic, or psychiatric disease, but the diagnosis is often missed or delayed. Once a diagnosis of Wilson disease is considered, reliable studies of copper variables can be carried out. After diagnosis, patients must receive anticopper treatment for the rest of their lives, to reduce copper levels and prevent copper reaccumulation. For life-long maintenance therapy, we recommend zinc acetate because of its complete efficacy and lack of toxicity; it acts by blocking copper absorption. For initial therapy of the acutely ill patient, no currently available therapy has proven to be ideal. A chelator-type drug, either penicillamine or trien, can be used for the initial therapy of patients who present with liver disease; transition to zinc acetate can then be made after a few months. For the initial therapy of acutely ill patients who present with neurologic disease, chelation should be avoided because neurologic worsening frequently occurs, probably due to redistribution of copper which temporarily raises the levels of copper in the brain. For initial treatment, zinc therapy is also not ideal because it is relatively slow-acting. A new experimental drug, tetrathiomolybdate, shows promise in the initial treatment of patients with Wilson disease. The major challenges ahead include closing the remaining therapeutic hiatuses, cloning and expressing the gene to understand its function, and improving clinical diagnosis so that therapy can be instituted as quickly as possible. PMID- 1635440 TI - Pneumocystis carinii infection. 1973. PMID- 1635441 TI - [Objective evaluation of respiratory ventilation at work by measuring peak expiratory flow rate (PEFR)]. AB - Eleven patients suffering from baker's asthma, 27 patients with bronchitis and 2 patients with suspected bronchial asthma resulting from occupational exposure to formaldehyde were subjected to a single blinded 3-day observation. Clinical symptoms' analysis and PEFR were performed to diagnose asthmatic symptoms at the workplaces. In all the patients with barker's asthma bronchoconstriction was observed as a result of exposure to formaldehyde on both "no drug" and "placebo" days. No bronchoconstriction on the "bronchodilator" day was observed. Reactions to other asthmatic and bronchitic patients differed significantly. The proposed model seems to be useful as a routine diagnostic procedure in occupational asthma. PMID- 1635442 TI - [Psychological evaluation of the effects of chronic occupational exposure of paint shop workers to the mixture of organic solvents]. AB - The aim of the study was to evaluate the psychological effects of chronic occupational exposure to the mixture of organic solvents containing xylene, toluene, n-butanol, butyl acetate, n-butyl acetate, ethyl acetate and cyclohexanone defined by MAC values. Thirty-four paint shop workers and 34 controls, matched according to sex, age, education and the type of work performed, were examined. The Neurobehavioral Core Test Battery (NCTB) was used in the study. In the exposed workers, a longer simple reaction time was observed, as well as reduced manual skills and impaired precision of the hand movements. PMID- 1635443 TI - [Peripheral vision in copper mine workers]. AB - Eighty-two copper mine workers were subjected to an examination performed twice a day. Field of vision and eye's resolving power were examined in all subjects. Preliminary examination was performed above ground before the miners started their work and later, after five hour's work under ground. During the follow-up examination the limitation of the field of vision was found in 64% of face foremen and in 13.6% of off-face miners. This limitation was observed in the lower temporal quadrants. The limitation is probably of central origin and is connected with the effects of occupational agents, eg. noise. The eye's resolving power assessed under ground was statistically remarkably lower than above ground. However, taking into consideration the inadequate lighting, one might expect more serious changes of this characteristic. PMID- 1635444 TI - [Acetylcholinesterase activity in erythrocytes of workers engaged in the production of iron-manganese alloys]. AB - The activity of acetylcholinesterase in the red blood cells of metallurgy workers producing iron-manganese alloys was statistically less significant than the activity of this enzyme in the control group. Work tenure and smoking intensity, measured using the smoking index method did not significantly affect the acetylcholinesterase activity in the worker's red blood cells (smoking index = number of packs of cigarettes smoked per day x years of smoking; one pack = 20 cigarettes). The results may point to malfunctions of the erythrocytes membranes caused by harmful substances in iron works producing iron-manganese alloys. PMID- 1635446 TI - [Biological markers--a new trend in evaluating the effects of the environment on the body]. AB - Deepening changes in the environment, resulting from the industrialization process, have a negative effect upon human health. They increase specific health effects and bring about higher incidence of common diseases. Biomarkers make it possible to evaluate the organism's reaction toward the hazardous effects of exposure to noxious chemicals of the environmental origin. Biomarkers reflect the changes in the exposed organisms and make it possible to assess exposure, its health effects and susceptibility to toxic agents. At the moment, research is under was aimed at finding biomarkers for the neoplastic process and determining the neurotoxic effects, changes in the reproductive system, immunotoxic effects as well as toxic changes in such organs as liver, kidneys and lungs. PMID- 1635445 TI - [International control of the quality of microscopic-numerical analysis of the levels of man-made mineral fibers (MMMF) in the air of the work area]. AB - In the years 1986-1990 the Institute of Occupational Medicine in Lodz (Department of Aerosols) participated in seven exchanges of preparations within the WHO/Euro MMMF Reference Scheme programme. The number of persons analysing the preparations increased from three, during the first exchange, to seven in the sixth. Markings in the 1st and 3rd exchange constituted two thirds of the reference markings. In the 2nd, 5th and 7th exchange the markings were similar, and in the 6th exchange they were lower than in the reference markings. According to the accepted system, the markings of the standardized density in four exchanges (2nd, 5th, 6th and 7th) were determined as class I (0.70-1.40), and in the remaining exchanges (1st, 3rd and 4th) of class II (0.50-2.00). PMID- 1635447 TI - [Risk of neoplasms among workers in the paper-cellulose industry]. AB - The results of various epidemiological research indicate that workers in the pulp and paper industry have an increased risk of developing and dying of malignant cancer with a specific location. The paper discusses recent studies in the area. The findings point to an increased risk of stomach cancer in workers occupationally exposed to pulp produced in the sulfite process. Workers making paper and cardboard are especially at risk for lung cancer. Some researchers signal a higher risk of lymphatic system cancer and stoma cancer. On the basis of existing data on exposure in the pulp and paper industry, it is impossible to determine the exact effects of exposure to a given compound or chemical. Assessment of exposure at particular work areas and analysis of data using the job exposure matrix is necessary. This should provide more information about cancerogenic compounds in the pulp and paper industry. PMID- 1635449 TI - Prediction of the carcinogenic potential of chemicals. PMID- 1635448 TI - [Principles of establishing the registries of chemical substances in the United States and Europe]. AB - The paper presents the principles of building up the inventories of chemical substances in the USA, the countries belonging to European Economic Community (EEC) and Austria. In all countries, the appropriate legal regulations putting the manufacturers and importers of chemicals under obligation to provide some strictly determined information underlie the decision to build up these inventories. The data provided usually inform of: manufacturer's name and address, chemical substance identity, production volume and ways of distribution. The paper presents also the criteria of selection of substances to be placed in the inventory, organizational scheme of building up the inventory and the ways of exacting the respective regulations. The inventories of chemical substances issued in the USA and Austria may serve as banks of information on the place, kind and quantity of chemical substances on the territory of the whole country. Based on these data a map of chemical hazards zones may be prepared which may adversely affect either human health or environment. The inventory of EEC countries may serve only as lists of chemicals occurring in the common market. PMID- 1635450 TI - Sensitivity of Salmonella typhimurium TA97a to the type of agar used for preparation of Vogel-Bonner plates. AB - Recent problems with the supply of Difco bacto agar have forced some laboratories to evaluate alternative agars for use in the Salmonella/microsome assay. This led to the independent observation in two laboratories (Boots and Glaxo) that Salmonella typhimurium TA97a is sensitive to certain types of agar that may be used to prepare Vogel-Bonner minimal medium plates. A programme of work was, therefore, undertaken to investigate this phenomenon; 9-aminoacridine hydrochloride (at Boots) and 4-nitro-o-phenylenediamine (at Glaxo) were tested against TA1537 and TA97a using Vogel-Bonner plates prepared with a number of different agars. Three agars (Lab M, Difco Bi-tek and Beckton Dickinson granulated) were identified which, although supporting normal growth of TA1537 revertant colonies, gave much reduced control counts and responses to the mutagens with TA97a. One agar, Becton Dickinson grade A, gave poor responses with TA1537 but produced satisfactory results with TA97a. In contrast to the Vogel Bonner plates, varying the type of agar used in the top agar overlays had little effect on the responses obtained. On the basis of these comparisons, Becton Dickinson purified agar was selected as a suitable alternative to Difco bacto and it was concluded that laboratories using agars other than these, or purchasing pre-poured plates without specifying the type of agar, should be made aware of potential problems with TA97a. PMID- 1635451 TI - Formation of thymidine adducts and cross-linking potential of 2-bromoacrolein, a reactive metabolite of tris(2,3-dibromopropyl)phosphate. AB - DNA-adduct formation by the mutagen 2-bromoacrolein (2BA) with DNA was studied. [3-3H]2BA was reacted with single-stranded (ss) DNA or double-stranded (ds) DNA and subsequently incubated with methoxylamine to convert an unstable 2BA:thymidine adduct (Meerman et al., Cancer Res., 49, 6174-6179, 1989) to a stable product. This product was identified in the study as 3-(2"-hydroxy-3" methoximpropyl)thymidine (HYMETH) by LC-MS. After extensive purification and enzymatic hydrolysis of modified ssDNA and dsDNA, approximately 5% of the covalently bound activity coeluted with added HYMETH standard in a reverse phase HPLC system. Because the unstable 2BA:thymidine adduct may have the potential to form cross-links, we investigated the reaction of this adduct with various nucleophiles in vitro. A reaction occurred between the adduct and cysteine, but not with lysine or deoxynucleosides. Reaction of 2BA with ssDNA in the presence of [3H]glutathione also resulted in the binding of radiolabelled GSH to DNA. These results indicate that the reactive aldehyde group of the adduct can react with thiol groups in proteins to form protein-DNA cross-links. Further, the possibility that tris- and bis-(2,3-dibromopropyl)phosphate (Tris-BP and Bis-BP) form such cross-links was examined in vivo in Drosophila. The results indicate that Tris-BP is a cross-linking agent, whereas Bis-BP is not. Inasmuch as Tris-BP is known to be metabolized rapidly to 2BA and Bis-BP, whereas Bis-BP forms 2BA only very slowly, suggests that in Drosophila DNA adducts are formed that cross link proteins. PMID- 1635452 TI - Use of batch and fed-batch fermentation for studies on the variation of glutathione content and its influence on the genotoxicity of methyl-nitro nitrosoguanidine in yeast. AB - We have applied fermenter techniques to analyse the variations of glutathione (GSH) content in cultures of the diploid strain D7 of Saccharomyces cerevisiae. Choosing various experimental conditions of controlled batch and fed-batch fermentation we give evidence that the GSH levels of the yeast cultures depend on growth phase, the carbon source supply and the carbon source metabolism in an unexpectedly complex manner. Additionally, we analysed yeast cells with low GSH levels which were obtained either by depleting GSH with chloroacetophenone (CN) chemically or by using a GSH-deficient diploid strain (gsh1/gsh1). In order to study the relevance of the factors influencing the GSH concentration for genotoxicity testing in yeast we have used N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) which is activated by GSH. We show that in cells which are GSH proficient the extent of genotoxicity of MNNG correlates well with the GSH levels in the cells. Conditions of high GSH content (stationary phase of growth) corresponds with high genotoxic activity of MNNG, whereas conditions of low GSH content as logarithmic growth, glucose repression, GSH deficiency caused by the gsh1 mutation and GSH depletion by CN treatment correspond with a very moderate genotoxic effect of MNNG. These findings emphasize the necessity to use metabolically highly standardized cells for genotoxicity testing, since the carbon source catabolism, the concentration of glucose, growth rate and possibly other parameters influence the metabolization of xenobiotic agents in yeast. PMID- 1635453 TI - Bacterial mutagenic evaluation of a series of 4' substituted derivatives of 3 benzylidenamino-5H-1,2,3-triazin[5,4b]indol-4-one. AB - The mutagenicity of ten triazinoindole derivatives was studied in bacteria. The compounds form part of a 3-(4'-substituted-benzylidenamino)-5H-1,2,3-triazin[5,4 b]in dol-4-one series and differ in the physicochemical properties of the substituent at the 4' position of the benzylidenamino group: -H, -OH, -COOH, OCH3, -COOCH3, -NHCOCH3, -C1, -NO2, -C6H5, and -OC6H5. They were tested in the TA97, TA98, TA100, and TA102 strains of Salmonella typhimurium, both with and without metabolic activation, using the preincubation procedure. Only the derivatives with phenyl and phenoxy substituents were non-mutagenic. The remaining compounds significantly increased the number of His+ revertants and showed three patterns of activity based upon their mutagenic potency and their response to metabolic activation. Size and hydrophobicity of the 4'-substituents are the physicochemical characteristics that most differentiate the mutagenic triazinoindole derivatives from the nonmutagenic ones. PMID- 1635454 TI - Influence of the triazine ring on the mutagenicity of triazinoindoles and some congeners. AB - Three compounds, which could be considered as precursors or derivatives of the 3 (4'-substituted-benzylidenamino)5H- 1,2,3-triazin[5,4b]indol-4-one series, were selected from the study of their mutagenic activity. Ames tests were performed study of their mutagenic activity. Ames tests were performed using the Salmonella typhimurium strains TA97, TA98, TA100, and TA102, according to the preincubation procedure, both with and without metabolic activation. The 3-amino-5H-1,2,3 triazin[5,4b]indol-4-one has been shown to be a strong S9-independent mutagen, which reverts frameshift and substitution mutations. Nevertheless its potency increases with the addition of microsomal fraction. In contrast, the 2-benzyliden 1-(3-aminoindol)-2-carbohydrazide and the 3-aminoindol-2-carbohydrazide congeners were not mutagenic. These results suggest that the 1,2,3-triazine ring is the principle substructure responsible for the mutagenicity of the triazinoindole congeners studied. PMID- 1635455 TI - Induction of ribonucleoside diphosphate reductase gene transcription by chemicals in Escherichia coli. AB - A fusion between the promoter of the nrdA gene of Escherichia coli and the lacZ gene has been constructed, and the induction of nrdA gene expression by 20 organic and 20 inorganic chemicals has been studied. The inducing compounds of the SOS genes, such as bleomycin, captan, ciprofloxacin, enoxacin, hydroxyurea, N methyl-N'-nitro-N-nitrosoguanidine, mitomycin C, nalidixic acid, ofloxacin and hexavalent chromium compounds also trigger the expression of the nrdA gene. Other chemicals such as aluminium, manganese and zinc salts, reported as negative in the SOS Chromotest, are also inducers of the nrdA gene. These results suggest that ribonucleoside diphosphate reductase transcription is increased by chemicals able to either block DNA synthesis or to alter the enzymes participating in the DNA replication. Induction of nrdA gene is an effect to be further considered in the study of alterations produced by physical or chemical treatments which act upon DNA metabolism. PMID- 1635456 TI - Effect of arsenite on the DNA repair of UV-irradiated Chinese hamster ovary cells. AB - Arsenite, an ubiquitous human carcinogen, has been shown to enhance the cytotoxicity, mutagenicity and clastogenicity of UV light in mammalian cells. Arsenite may exert its co-genotoxic effects by inhibiting DNA repair. Results from alkaline sucrose gradient sedimentation show that arsenite did not accumulate UV-induced DNA strand breaks in Chinese hamster ovary (CHO) K1 cells as aphidicolin plus hydroxyurea (HU) did. These data indicate that arsenite did not inhibit the activity of DNA polymerase alpha in UV repair. Treatment with arsenite before UV irradiation slightly reduced the DNA strand breaks accumulated by cytosine beta-D-arabinofuranoside (AraC) plus HU. This effect implies that arsenite only slightly inhibited the incision of UV-induced DNA adducts. The low molecular weight DNA accumulated by post-UV incubation with AraC plus HU shifted to high molecular weight upon the incubation of cells in drug-free medium, but this shifting was prohibited by the presence of arsenite. This suggests that arsenite inhibited the rejoining of DNA strand breaks. When a pulse-chase labelling procedure was applied on UV-irradiated cells, the chain elongation of nascent DNA was strongly inhibited by post-incubation with arsenite. These data show that arsenite inhibited post-replication repair in UV-irradiated cells. Therefore, the steps inhibited by arsenite in UV-induced DNA repair in CHO K1 cells are different from human fibroblasts in which the inhibition of excision of pyrimidine dimers by arsenite was reported to be the major target. PMID- 1635457 TI - Micronuclei induced by 2-chlorobenzylidene malonitrile contain single chromosomes as demonstrated by the combined use of flow cytometry and immunofluorescent staining with anti-kinetochore antibodies. AB - The effects of the tear gas 2-chlorobenzylidene malonitrile (CS) on micronucleus induction and cell cycle kinetics were studied in Chinese hamster and Ehrlich ascites tumour cells using flow cytometric analysis of micronuclei and nuclei in suspension, and indirect immunofluorescent staining of kinetochores in micronuclei. In both cell lines CS induced a concentration-dependent inhibition of the fraction of cells in mitosis as observed by simultaneous flow cytometric measurements of DNA content and side scatter intensities of cell nuclei. Micronucleus frequency increased during the delayed division of cells accumulated by CS in mitosis and reached a plateau when most of these cells have divided. The height of this plateau depended on the CS concentration. Results obtained by flow cytometric analysis of the frequency of CS-induced micronuclei did not agree quantitatively with results obtained by microscopic analysis due to cells showing CS-induced fragmented nuclei. Nearly all CS-induced micronuclei exhibited kinetochores, the majority of which (60-70%) showed one kinetochore per micronucleus implying the presence of a single metaphase chromosome in these micronuclei. DNA distributions of micronuclei measured by flow cytometry showed pronounced peaks corresponding to the DNA distribution of chromosomes measured by flow karyotyping. Even micronuclei containing two of the large chromosomes could be observed as distinct peaks in the distributions. The combined results of flow cytometric analysis of micronucleus distributions and immunofluorescence staining of kinetochores in micronuclei suggest that CS induces micronuclei mainly by damaging the spindle fibres of single chromosomes during mitosis, thus possibly leading to aneuploidy and polyploidy. PMID- 1635458 TI - Aneuploidy induction in mouse spermatocytes. AB - Assays for aneuploidy are being developed within a coordinated research program sponsored by the Commission of the European Communities. The 10 known and suspect spindle poisons colchicine (COL), econazole (EZ), chloral hydrate (CH), hydroquinone (HQ), diazepam (DZ), thiabendazole (TB), cadmium chloride (CD), pyrimethamine (PY), thimerosal (TM) and vinblastine (VBL) were tested for aneuploidy induction in male germ cells. Two different criteria were used for the evaluation of slides from testicular material of (102/El x C3H/El)F1 mice at different times (6, 14 and 22 h) after treatment with different doses of each of the test chemicals. Secondary spermatocytes of mice were evaluated by chromosome counting to determine the induction of hyperploidy. The proportions of spermatogonial mitoses, first and second meiotic metaphases were determined in order to recognize an effect of the test chemicals on testicular cell proliferation. COL, EZ, CH, HQ and VBL clearly increased the frequencies of hyperploid secondary spermatocytes which indicated non-disjunction induction during the first meiotic division. DZ and CD were less effective but significantly positive (P less than 0.05). Concomitantly, COL, EZ, CH, HQ, DZ, CD and VBL induced meiotic delay in primary and/or secondary spermatocytes. It is concluded that meiotic delay may be indicative for aneuploidy induction and the evaluation of changes in testicular cell proliferation described here could serve as a prescreen and partially substitute the time-consuming counting of metaphase chromosomes in secondary spermatocytes. PMID- 1635459 TI - Study on the mutagenicity of brandy with the Ara test. AB - The forward mutation assay to L-arabinose resistance (Ara test) in Salmonella typhimurium was used to demonstrate that evaporated residues of brandy had direct acting mutagenic activity. The mutagenicity covered a 100-fold range, from 13482 to 127 AraR induced mutants/ml brandy equivalent. Rat liver S9 mix suppressed the mutagenic activity of brandy in the Ara test. The inactivating capacity was independent of microsomal monoxygenase enzymes and appeared to be mediated through a heat stable component of the S9 fraction. Catalase was identified as the putative S9 component responsible for its inactivating capacity. The implication of reactive oxygen species in the direct-acting mutagenicity of brandy was supported by the higher sensitivity of Escherichia coli bacterial strains deficient in two major cellular antioxidant defense (glutathione and/or catalase) compared to their parental wild-type. Phenolic compounds of a polar nature could be responsible for the mutagenicity through the production of reactive oxygen intermediates. Non-matured beverages (gin and non-matured rum) were non-mutagenic. It is conceivable that mutagenic phenolics might be extracted from the wood during maturation in the barrel. Autoxidation of phenolic compounds could be a common mechanism in the mutagenicity of complex mixtures of plant origin. PMID- 1635461 TI - Industrial Genetic Toxicology Discussion Group. Report of the meeting on 'Practical Experiences with Regulatory Mutagenicity Guidelines'. PMID- 1635460 TI - Chromosomal localization of human O6-methylguanine-DNA methyltransferase (MGMT) gene by in situ hybridization. AB - Recombinant lambda phage DNA containing segments of human O6-methylguanine-DNA transferase gene was employed to localize this gene among the human chromosomes using non-radioactive in situ hybridization technique. This gene was found to be present at the telomeric end, 26q, of the long arm of the chromosome 10. PMID- 1635462 TI - Toward normative expert systems: Part II. Probability-based representations for efficient knowledge acquisition and inference. AB - We address practical issues concerning the construction and use of decision theoretic or normative expert systems for diagnosis. In particular, we examine Pathfinder, a normative expert system that assists surgical pathologists with the diagnosis of lymph-node diseases, and discuss the representation of dependencies among pieces of evidence within this system. We describe the belief network, a graphical representation of probabilistic dependencies. We see how Pathfinder uses a belief network to construct differential diagnosis efficiently, even when there are dependencies among pieces of evidence. In addition, we introduce an extension of the belief-network representation called a similarity network, a tool for constructing large and complex belief networks. The representation allows a user to construct independent belief networks for subsets of a given domain. A valid belief network for the entire domain can then be constructed from the individual belief networks. We also introduce the partition, a graphical representation that facilitates the assessment of probabilities associated with a belief network. We show that the similarity-network and partition representations made practical the construction of Pathfinder. PMID- 1635463 TI - Natural language processing and semantical representation of medical texts. AB - For medical records, the challenge for the present decade is Natural Language Processing (NLP) of texts, and the construction of an adequate Knowledge Representation. This article describes the components of an NLP system, which is currently being developed in the Geneva Hospital, and within the European Community's AIM programme. They are: a Natural Language Analyser, a Conceptual Graphs Builder, a Data Base Storage component, a Query Processor, a Natural Language Generator and, in addition, a Translator, a Diagnosis Encoding System and a Literature Indexing System. Taking advantage of a closed domain of knowledge, defined around a medical specialty, a method called proximity processing has been developed. In this situation no parser of the initial text is needed, and the system is based on semantical information of near words in sentences. The benefits are: easy implementation, portability between languages, robustness towards badly-formed sentences, and a sound representation using conceptual graphs. PMID- 1635464 TI - Possibilities of software phantoms for quality control of KBS in nuclear medicine. AB - The assessment of the results of a "knowledge-based system" (KBS) for quality control is a basic requirement for clinical application: Large numbers of test studies are necessary in order to cover as widely as possible the spectrum of cases to be analyzed by the KBS. The use of original patient data as test data is one possibility, but real data are provided unevenly. This is due to the set of characteristics which are relevant to the analysis. Data are available in a limited quantity only. This implies a remaining set of unvalidated cases which are not represented in the data pool. The software phantom is an approach towards systematically guided validation. It permits the generation of test data adjusted to the demands of the validation. PMID- 1635465 TI - Data modeling for immunological and clinical data of leukemia and myasthenia patients. AB - In this study it was investigated whether and to what extent semantic data models and their methods for data modeling are useful for adequate representation and integration of immunological and clinical data. To that end the special research program in leukemia research and immunogenetics (SFB 120) of the University of Tubingen was taken as an example. Based on the semantic data model RM/T we propose the design of a database system, report on its realization, and discuss this approach. Using a semantic data model, the quality of data increased considerably. This means, for instance, that the integration of the molecular biological knowledge allows a better control of the person-related results. Hence, the decisions based of these data may have greater validity and the treatment on leukemia patients can be improved. Furthermore, the elucidation of immune mechanisms concerning auto-immune diseases could be improved. PMID- 1635466 TI - Eurosentinel: development of an international sentinel network of general practitioners. AB - The Eurosentinel project was a European concerted action. It started in June 1988 and ended in June 1991. Its purpose was to coordinate activities in the field of sentinel practices with GPs and the ultimate goal was to establish a real European network of sentinel practices. This paper deals with the purposes of the project, the studies carried out in the frame of the project, and an evaluation of three years Eurosentinel. PMID- 1635467 TI - Use of two online services as drug information sources for health professionals. AB - The utility of the online computer services BRS Colleague and Dialog Medical Connection, when used primarily as drug information sources by physicians, nurses, and pharmacists and attitudes toward their use, are described. Study sites included office-based medical practices, a university clinic family medicine group, and a university clinical pharmacy department. Participants had access to either of the computer services during two 9 1/2-month periods. All searches were automatically recorded and analyzed. A total of 1,112 search sessions were conducted (78% by pharmacists, 16% by nurses, 6% by physicians) by 38 of 65 participants. Information which completely answered questions was found for slightly less than one-third of searches. Errors occurred in about 81% of searches which retrieved incomplete information. Lack of time was a major factor which limited use of the services, and infrequent users felt that the services did not fit in well with their daily work routine. PMID- 1635468 TI - A new paradigm of medical informatics. PMID- 1635469 TI - Expert system design in hematology diagnosis. AB - A two-part study was designed to test the hypothesis that sufficient information is available from a modern hematology analyzer (the Coulter STKS) to reach a reliable intermediate conclusion which can be used as input to the next decision making level in the design of a high-performance expert system for hematology diagnosis. In phase one, we analyzed the performance of three probabilistic systems (using Bayes' rule) which interpret STKS data: a control system which took the traditional approach of classifying cases into specific diagnoses, and two test systems which were designed to reach only an intermediate conclusion but not a final diagnosis. One of the test systems classified cases into "textbook categories" of disease and the other utilized defined diagnostic patterns. The systems were tested with 150 cases. The pattern approach ranked the correct choice first in 141 of 150 cases (94%). In phase two, we abandoned Bayes' rule, reformulated the pattern approach into a heuristic classification system, and tested its reliability on 820 cases. The algorithm of the reformulated system was able to classify all 820 cases into the same predominant pattern as a panel of three experienced laboratory hematologists. PMID- 1635470 TI - Toward normative expert systems: Part I. The Pathfinder project. AB - Pathfinder is an expert system that assists surgical pathologists with the diagnosis of lymph-node diseases. The program is one of a growing number of normative expert systems that use probability and decision theory to acquire, represent, manipulate, and explain uncertain medical knowledge. In this article, we describe Pathfinder and our research in uncertain-reasoning paradigms that was stimulated by the development of the program. We discuss limitations with early decision-theoretic methods for reasoning under uncertainty and our initial attempts to use non-decision-theoretic methods. Then, we describe experimental and theoretical results that directed us to return to reasoning methods based in probability and decision theory. PMID- 1635471 TI - Anti-oxidant therapy improves microvascular ultrastructure and perfusion in postischemic myocardium. AB - To determine the contribution of oxygen-derived free radicals to the changes in microvascular structure and function which follow reperfusion of ischemic myocardium, isolated perfused rat hearts were subjected to 15 or 45 min of global ischemia followed by 5 min of oxygenated reperfusion. Hearts were then fixed by perfusion with glutaraldehyde and perfused with nuclear track photographic emulsion to identify competent capillaries in scanning and transmission electron micrographs. Reperfusion after 15 min caused a significant reduction in the density of competent capillaries in the subendocardial third of the left ventricle, but this reduction was lessened but not eliminated by the addition of 0.61 mmole/liter desferrioxamine, but not by 60,000 U/liter superoxide dismutase plus 60,000 U/liter catalase, to the perfusate. After 45 min of ischemia both interventions prevented the myocyte swelling, endothelial cell changes, bleb formation, and reduction in microvascular lumina characteristic of unprotected reperfusion, but only desferrioxamine significantly improved microvascular competence. This suggests that the hydroxyl radical rather than superoxide and/or hydrogen peroxide has a pathogenic role, although desferrioxamine may have other effects as nonspecific chelator. Postischemic reductions in capillary function also occur in reversibly injured myocardium in the absence of structural abnormality. Preventing postischemic microvascular incompetence has the potential to minimize ischemic cell injury and to enhance repair following myocardial infarction, but it also may increase the risk of hemorrhage from venules. PMID- 1635472 TI - An evaluation of skin capillary blood flow determinations in neonates using a computerized videophotometric method. AB - Dynamic capillaroscopy has been shown to give valid measurements of skin capillary blood flow in adults. The aim of this investigation is to evaluate the accuracy of the method when applied to studies in newborn infants. A computerized videophotometric technique was used to measure the skin capillary blood cell velocity (CBV) and the capillary erythrocyte column diameter at 64 standardized locations in 16 nailfold capillaries in five subjects. To estimate the method's reliability, we calculated the coefficient of variation (CV = 1 SD/mean x 100%) for repeated measurements at each location. The CV for CBV determinations was found to be 3.4% (0.9-13%) and the corresponding value for capillary diameter measurements was 6.7% (0.5-12%) (median and range). Although the CBV and diameter values were found to vary along the course of the capillary, the volume flow of blood cells was assumed to be the same in simultaneously studied but different sections of the capillary. The paired CBV and diameter observations were therefore used to calculate blood cell flow values at an average of four different intracapillary locations. To estimate the method's validity, the CV for these repeated flow calculations was determined and found to be 7.5% (3.2-26%). We conclude that the age-specific characteristics in neonates, mainly a high hematocrit and short, irregular skin capillary loops, do not limit the feasibility and accuracy of videophotometric microscopy for dynamic microcirculatory studies in neonates. PMID- 1635473 TI - Repeated measurement variation and precision of laser Doppler flowmetry measurements. AB - The repeated measurement variation of laser Doppler flowmetry (LDF) recordings is essential for the precision level of the method in the assessment of tissue perfusion. The objective of this paper was to discuss the practical consequences of this problem by presenting a statistical method which can be used to estimate the number of replicates needed to reach a certain precision standard. By a repeated measures analysis of variance with a single-factor design, the mean variation of repeated measurements and its standard deviation were estimated. This estimate was used for simulation of a 95% confidence interval with length defined as a percentage of the mean of repeated measurements. The analyses were made in LDF samples performed in skin, gastric mucosa, and pig kidney in order to exemplify the use of the method. Paired values gave an unacceptable precision estimate in all tissues, but by increasing the number of replicates, the estimated precision was greatly enhanced. A preliminary recommendation for the practical use of LDF in the assessment of tissue perfusion is to perform at least four to six repeated measurements. Further studies are needed in order to establish methodological standards. The presented statistical considerations could also be relevant for other procedures used in microvascular research. PMID- 1635474 TI - Coronary microvascular response to exogenously administered and endogenously released acetylcholine. AB - The objectives of the present study were first, to determine the coronary microvascular response to vagal stimulation and to compare it to exogenously administered acetylcholine, and second, to determine the microvascular response to larger doses of acetylcholine which preferentially increase subendocardial blood flow. In anesthetized cats and dogs, the left ventricular epicardial vasculature was visualized in mid-diastole with stroboscopic epi-illumination. Myocardial perfusion was measured with the radioactive microsphere technique. In cats microvascular diameters were measured at control and following bilateral vagal nerve stimulation (5-30 Hz) or left atrial infusion of acetylcholine (0.4 1.0 micrograms/kg/min). Aortic pressure and heart rate (A-V-sequential pacing) were maintained constant. Vagal stimulation (n = 13) increased myocardial perfusion by 25 +/- 9% (control: 161 +/- 17 ml/min x 100 g). Acetylcholine (n = 13) produced a similar increase in myocardial flow (control: 185 +/- 16 ml/min x 100 g, 30 +/- 9%). Both vagal stimulation and acetylcholine dilated all size arteries and arterioles (51-410 microns; 5 +/- 1% and 11 +/- 2%, respectively). In dogs intracoronary administration of acetylcholine (10 micrograms/min) that increased myocardial flow twofold (control: 129 +/- 7 ml/min x 100 g; 10 micrograms/min: 263 +/- 26 ml/min x 100 g) and increased the endo/epi flow ratio also dilated all vessel sizes. In conclusion, vagal stimulation and exogenously administered acetylcholine produce similar effects on the coronary microcirculation and dilate all size classes of arteries and arterioles in a similar manner. Intracoronary infusion of acetylcholine which preferentially increases subendocardial blood flow also dilates all size classes of microvessels. Thus, the ability of acetylcholine to preferentially increase subendocardial blood flow cannot be explained by a selective dilation of a particular size class of arterioles. These data suggest that neurally released acetylcholine can diffuse to the endothelial layer to release vasodilator substances in vivo. PMID- 1635475 TI - Modeling transient exchange in mesentery. AB - In this paper, a mathematical model of interstitial transport and microvascular exchange within a rigid mesenteric tissue segment is employed to simulate the transient exchange of fluid and plasma proteins following two systemic disturbances: hypoproteinemia and venous congestion. In each case, the model system behavior is studied as a function of interstitial plasma protein transport mechanisms and mesothelial transport properties. Plasma protein washout was generally predicted in cases of hypoproteinemia. However, following venous congestion, the transient change in interstitial plasma protein content also depended on the relative sieving properties of the filtering and draining boundaries. When these boundaries display similar sieving characteristics, the interstitial plasma protein content increases following the disturbance. Such behavior may have some bearing on transient exchange in the hepatic microcirculation during venous congestion. PMID- 1635476 TI - Use of fluorescently labeled erythrocytes and digital cross-correlation for the measurement of flow velocity in the cerebral microcirculation. PMID- 1635477 TI - Fiber matrix model reanalysis: matrix exclusion limits define effective pore radius describing capillary and glomerular permselectivity. PMID- 1635478 TI - Perfusate composition modulates in vitro renal microvascular pressure responsiveness in a segment-specific manner. PMID- 1635479 TI - An extension of the fiber matrix model of vascular permeability. PMID- 1635480 TI - Capillary as a communicating medium in the microvasculature. PMID- 1635481 TI - [The use of pulsed field electrophoresis using diversely directed electrical fields for establishing the degree of similarity of three Pseudomonas cultures]. AB - It has been shown that from the group of three restriction endonucleases (XbaI, Uba 78I, DraI) only XbaI digests the native Pseudomonas genomic DNA into the number of fragments, sufficient for their comparative analysis. Optimal electrophoresis conditions were adjusted for the better DNA restricts separation. Each Pseudomonas culture gives unique patterns of DNA restriction. The calculation of the conservative fragments fraction content in the samples led us to the conclusion that P. fluorescens differs equally from both P. fluorescens 80 and P. alcaligenes. The P. fluorescens 80 DNA contains a relatively larger number of fragments equal in size with those of P. alcaligenes DNA, than DNA of P. fluorescens. We have concluded that the systematics of the Pseudomonas genus is still imperfect and that the analysis of DNA restriction patterns is necessary for the estimation of the similarity level of cultures studied. PMID- 1635482 TI - [The nature of stability of yeast cells to drying]. AB - The residual water and dry matter condition in the lyophilized biomass of the yeast Saccharomyces cerevisiae was studied by NMR-relaxation technique. It was shown that the slow component of the transverse magnetization NMR signal spectrum corresponding to the so-called "isolated mobile water" was caused in fact by the interaction of the disaccharide trehalose with the cell biopolymers. The big amount of hydrogen bonds formed by trehalose and their three-dimensional orientation closed to the orientation in water clusters assure the valuable functioning of this disaccharide during the process of removing water out of cells. When stationary phase yeast biomass containing a lot of trehalose was dried the cell organelles condition remained practically unchanged what led to the high resistance of such cells to dehydration. PMID- 1635483 TI - Anaesthesia in obstetrics--how safe? PMID- 1635484 TI - Frozen embryos: another population explosion? PMID- 1635485 TI - Azoospermia. PMID- 1635486 TI - Rural mental health. PMID- 1635487 TI - Antenatal care of low risk obstetric patients by midwives. A randomised controlled trial. AB - OBJECTIVES: To assess the practicality, acceptability to patients and salary costs of the antenatal care of low risk obstetric patients by midwives. DESIGN: A randomised controlled trial. SETTING: The antenatal clinic at Westmead Hospital, a teaching hospital of the University of Sydney in western Sydney. PATIENTS: From January 1989 until November 1990, 89 women booking for full antenatal care at Westmead Hospital and classified as low risk were randomly allocated to one of two groups. Group 1 (43 patients) had their antenatal care provided by registered midwives. Group 2 (46 patients) had their antenatal care provided by an obstetrician (either Visiting Medical Officer or Staff Specialist) in a routine hospital antenatal clinic. INTERVENTIONS: Patients in the midwives' clinic were seen by an obstetrician at their first visit to the antenatal clinic and again at 30 weeks and at 40 weeks. MAIN OUTCOME MEASURES: These were the salary costs of each clinic and the patients' levels of satisfaction. Maternal and neonatal indicators, delivery details and analgesic requirements were also considered. These indicators were planned before data collection commenced. RESULTS: The major differences found were a 28% to 68% salary cost saving and that patients cared for by midwives showed appreciation of the continuity of care and information given at the midwives' clinic. CONCLUSIONS: The care of low risk obstetric patients by midwives in a midwives' clinic showed salary cost savings and high patient acceptance. PMID- 1635488 TI - Comparative study of mammography and mammary serum antigen estimation for breast cancer screening. AB - OBJECTIVE: To compare mammary serum antigen (MSA) levels with mammography as a screening test for breast cancer. To determine the value of MSA testing to decrease the need for women to undergo mammography. DESIGN: A blind prospective comparison of MSA levels and mammography to detect breast cancer. SETTING: Royal Women's Hospital Breast Cancer Screening Clinic. Women were mainly self-referred. RESULTS: MSA levels had a wide range in normal women and women with mammography detected breast cancer. Mean MSA levels in women with breast cancer reflected tumour volume, but a wide range was again seen. At 60% specificity, the sensitivity of an elevated MSA level for breast cancer was 63% for invasive cancer and zero for in-situ disease. MSA levels were modestly but significantly elevated in smokers over non-smokers. CONCLUSION: The MSA level is an insufficiently sensitive or specific marker to have a role in screening for breast cancer. PMID- 1635489 TI - In-vitro fertilisation and neonatal ventilator use in a tertiary perinatal centre. AB - OBJECTIVE: To determine the contribution of livebirths resulting from in-vitro fertilisation and related technologies (IVF) to the use of neonatal ventilator beds. DESIGN: A retrospective review of records of all livebirths from our hospital's IVF program and all IVF infants receiving mechanical ventilation in our neonatal intensive care unit for the period 1985-1989. We also reviewed records of labour ward deliveries, neonatal intensive care unit admissions and transfer requests in order to obtain comparative data for livebirths of non-IVF infants whose mothers had been booked to deliver in our hospital. SETTING: A tertiary perinatal centre with a large IVF program and a Level 3 neonatal intensive care unit. RESULTS: IVF livebirths accounted for 5.1% of total ventilator bed days. Compared with non-IVF booked livebirths, IVF babies were more likely to require ventilation (odds ratio, 7.41; P less than 0.0001) and used more ventilator bed days per 100 livebirths (rate ratio, 9.63; P less than 0.0001), largely due to preterm delivery of multiple pregnancies; 42.3% of IVF babies who required ventilation were from triplet births and 38.5% from twin births. Nevertheless, even IVF singletons used more ventilator bed days per 100 livebirths than non-IVF booked livebirths (rate ratio, 2.78; P less than 0.0001). IVF livebirths accounted for 9.9% of the 78% increase in ventilator bed days used in 1989 compared with 1985. CONCLUSIONS: IVF livebirths accounted for only a small percentage of the overall use of neonatal ventilator beds, but consumed relatively more of such resources per livebirth than did non-IVF livebirths. The degree of risk of requiring ventilation is directly related to the number of infants in a multiple pregnancy, but even IVF singletons are at a relatively high risk of requiring ventilation. PMID- 1635490 TI - Increased risk of postnatal depression after emergency caesarean section. AB - OBJECTIVE: To examine whether women having an emergency caesarean section are at increased risk of developing postnatal depression at one, three and six months postpartum. DESIGN: Participants were part of a larger study examining the relationship between personality dysfunction and postnatal depression. All women were recruited at an antenatal clinic in the first trimester of their pregnancy. These women were followed up at one, three and six months postpartum to identify cases of postnatal depression, defined by the Edinburgh Postnatal Depression Scale (EPDS). RESULTS: Data were collected from 188 women, who were divided into three groups by method of delivery: 21 women had an emergency caesarean section, 49 had a forceps delivery and 118 had a spontaneous vaginal delivery. Comparison of the groups indicated a significant difference at three months postpartum only. Women having an emergency caesarean section had significantly higher EPDS scores than women who had forceps or spontaneous vaginal delivery (9.15 +/- 6.18 v. 5.05 +/- 3.81 v. 5.79 +/- 4.47; F(2,143) = 4.2, P less than 0.02). Analysis of postnatal depression at three months indicated that women in the emergency caesarean section group had a relative risk of 6.82 (95% confidence interval, 2.85-16.15) compared with women in the other groups. CONCLUSIONS: When compared with women having spontaneous vaginal or forceps deliveries, women having an emergency caesarean section had more than six times the risk of developing postnatal depression three months postpartum. Special attention to this group appears warranted. PMID- 1635491 TI - Oestrogen and the breast. 1. Myths about oestrogen and breast cancer. PMID- 1635492 TI - A graduate diploma in family medicine by distance education. PMID- 1635493 TI - A master's degree in family medicine. PMID- 1635494 TI - Health status and lifestyle in elderly Hawaii Japanese and Australian men. Exploring known differences in longevity. AB - OBJECTIVE: To contrast health status and lifestyle in two elderly populations with differing longevity. DESIGN: Comparison of two cross-sectional data sets. SETTING: Non-institutionalised subjects. SUBJECTS: Men aged 60-81 years resident in Dubbo, New South Wales (n = 1183, 1988-1989) and Japanese men of the same ages resident in Hawaii (n = 1376, 1980-1982). MAIN OUTCOME MEASURES: Cardiovascular and non-cardiovascular disease prevalence, risk factors, social and health status. RESULTS: A history of heart attack, angina and stroke was twice as prevalent in Dubbo men as in Hawaii Japanese. Other diseases were many times more prevalent in Dubbo--liver disease sixfold, prostate and renal disease twofold, and arthritis 1.5-fold. Hypercholesterolaemia and untreated hypertension were more prevalent in Dubbo (threefold and 1.5-fold respectively). Current smoking was similar in both groups, while diabetes was twice as prevalent in the Hawaii Japanese. More Dubbo men were widowed or lived alone, and fewer remained in paid employment. Dubbo men had more limited physical mobility. CONCLUSIONS: Elderly Dubbo men have an excess of cardiovascular disease and associated risk factors, as well as an excess of non-cardiovascular disease, compared with Hawaii Japanese. This may account, in part, for a higher total mortality rate in elderly Australians compared with Japanese. Some of this disease burden may be amenable to risk factor intervention. PMID- 1635495 TI - Acute adrenal insufficiency secondary to heparin-induced thrombocytopenia thrombosis syndrome. AB - OBJECTIVE: To present a case of acute adrenal insufficiency secondary to heparin induced thrombocytopenia-thrombosis syndrome (HITTS), an important though rare complication of heparin therapy. CLINICAL FEATURES: A 69-year-old woman developed HITTS secondary to low dose heparin administered subcutaneously as prophylaxis against deep venous thrombosis. This followed a revision of a knee replacement. The first manifestation of HITTS was the development of pulmonary emboli in the setting of a falling platelet count. Bilateral adrenal haemorrhages complicated her course resulting in acute adrenal insufficiency. Non-specific symptoms dominated the clinical picture, with fever, nausea, abdominal pain and vomiting. Symptomatic postural hypotension was noted later in the course of her illness. INTERVENTION AND OUTCOME: The diagnosis of adrenal insufficiency was confirmed by short Synacthen test plus computed tomographic scanning which demonstrated bilateral adrenal haemorrhages. Steroid replacement resulted in rapid clinical improvement. CONCLUSIONS: This case demonstrates one of the life threatening complications that may occur with heparin even in prophylactic doses. Regular platelet counts are essential to detect heparin-induced thrombocytopenia at an early stage. PMID- 1635496 TI - Whiplash in Australia: illness or injury? AB - OBJECTIVE: To provide a perspective on "whiplash" injury in Australia by examining conflicting evidence, which suggests on the one hand that the disorder is a culturally conditioned and legally sanctioned illness and on the other, that it is an occult injury which can cause chronic pain. DATA SOURCES: The published English language literature derived from MEDLINE covering epidemiological, pathogenetic and psychological aspects of "whiplash" injury, post-traumatic stress disorder, abnormal illness behaviour and iatrogenicity; the Australian legal literature; the printed news media; the Transport Accident Commission of Victoria and the State Government Insurance Commission of South Australia. DATA SYNTHESIS AND CONCLUSIONS: Comparative studies suggest that "whiplash" is an illness reinforced by legal and social sanction. Evidence from Victoria indicates that the reported incidence of "whiplash" can be reduced by minor legislative change. Occult injury to cervical intervertebral discs, vertebral end plates and cervical zygapophysial joints may be responsible for "whiplash" symptoms in some who are involved in motor vehicle accidents. This is likely to be confined to a small number of those involved in unexpected rear-end collisions. PMID- 1635497 TI - The evolution of computer viruses. Part 1: A compelling analogy with biological virus. PMID- 1635498 TI - Immunosuppression in transplantation. PMID- 1635500 TI - Community attitudes to smoking in restaurants. PMID- 1635499 TI - The effect of oestrogen on the female cardiovascular system. AB - OBJECTIVE: To review the present state of knowledge regarding the effect of oestrogen on the female cardiovascular system (e.g. atherosclerosis, myocardial infarction, hypertension and thrombosis). DATA SOURCES: Over 100 articles (most published over the last 10 years) were reviewed. They included epidemiological, biochemical, physiological, animal and clinical studies which related to the effect oestrogens have on the cardiovascular system of postmenopausal women. These data contained a wide cross-section of results and outcomes and each study was summarised to provide the most relevant information. Where a particular study provided an opinion or result at variance with the majority opinion, that study has been discussed in greater detail. STUDY SELECTION: All published papers which appeared to be relevant to an understanding of the clinical implications of oestrogen replacement therapy and its impact on the female cardiovascular system were included in this analysis. Some papers which appeared to repeat data and results previously published were not included. DATA SYNTHESIS: The overwhelming eight of evidence from this literature review supports the concept that oestrogen reduces the risk of atherosclerosis and myocardial infarction. It also confirms that postmenopausal "natural" oestrogen is a vasodilating agent which will lead to a fall in blood pressure and an improvement in blood flow and the pulsatility index. Although oral oestrogen did appear to increase thrombogenic activity, there was no clinical evidence that "natural" oestrogen taken after the menopause increased the risk of venous thrombosis. CONCLUSIONS: The consensus of the published data is that oestrogen conveys a highly protective effect on the cardiovascular system of postmenopausal women. There will be a reduction of up to 50% in myocardial infarction and stroke, a reduction in the incidence of hypertension and an improvement in blood flow. Some of the data suggest that even for women who have suffered from an infarct, their long-term survival is enhanced by oestrogen therapy. The medical myth that oestrogen has a deleterious effect on the cardiovascular system of women is finally laid to rest. PMID- 1635501 TI - Melioidosis in Sydney. PMID- 1635502 TI - Lead toxicity in cats. PMID- 1635503 TI - HIV testing of homosexual and bisexual men. PMID- 1635504 TI - RSI, whiplash and cervicobrachial pain. PMID- 1635505 TI - Medical aspects of euthanasia. PMID- 1635506 TI - Male homosexuality. PMID- 1635507 TI - Cultural variations in mental health. PMID- 1635508 TI - Cultural variations in mental health. PMID- 1635509 TI - Gonococcal arthritis: a Bangkok connection. PMID- 1635510 TI - Testing after vasectomy. PMID- 1635511 TI - Adolescent use of sun-protection measures. PMID- 1635512 TI - The New World screw-worm and other exotic myiases in Australia. PMID- 1635513 TI - Child abuse: does prosecution serve any useful purpose? PMID- 1635514 TI - The Privy Council and the professional foul. PMID- 1635515 TI - Environmental radiation risks near Sellafield judged trivial--the Merlin case. PMID- 1635516 TI - The legal consequences of shock. 1933. PMID- 1635517 TI - [Endoscopic sub-fascial perforant vein dissection in the treatment concept of primary varicose veins]. AB - Subfascial dividing of insufficient perforating veins is considered the most effective therapeutic principle in the treatment of primary varicosis and postthrombotic changes or varicosis-related trophic disturbances of the skin. A new endoscopic technique allows these veins to be sectioned under direct vision, with little trauma. Between November, 1986 and August 1991, 74 patients underwent endoscopic sectioning of perforating veins in a total of 106 legs. In 100 legs, the procedure was combined with a conventional stripping operation. The perforating veins divided most frequently involved the Cockett group (223), the 24 cm perforating vein (86) and the Boyd group (83). In three legs (2.8%) showing trophic skin changes in the lower leg area impaired wound healing was seen postoperatively. Follow-up examination carried out 27 months after the procedure revealed insufficient perforating veins in two of the legs treated. New varices were seen in nine legs. In terms of staging of chronic venous insufficiency, either a more favourable stage or complete healing can be achieved in 90 of the cases. PMID- 1635518 TI - [Image analysis of DNA cytometry in tumors of the upper gastrointestinal tract]. AB - The prognostic influence on the DNA content was investigated in 189 patients (esophagus carcinoma n = 45, gastric cancer n = 103, pancreatic cancer n = 41) who underwent a curative resection. In a multivariate analysis the DNA content had a strong as well as an independent influence on the prognosis in esophagus cancer and in pancreatic carcinoma. In gastric cancer, the DNA content had no influence on the prognosis. These results show that the DNA content of the tumor cells, as a measurement of the numerous chromosomal aberrations, well reflects the aggressiveness of the tumor growth in esophagus- and pancreatic cancer. In these tumors it represents the decisive criteria for the prognostic judgement. PMID- 1635519 TI - [Morbidity and fatality of surgery for stomach cancer. Results of a prospective study on the importance of various risk factors]. AB - A total of 172 patients with cancer of the stomach presenting between 1986 and 1990 were entered into a prospective study. Total gastrectomy including extended lymph node dissection and splenectomy was done in 84 patients, simply gastrectomy in 28, resection in 29, and other operative procedures with no resection in 31 patients. Postoperative morbidity rates were 38%, 21%, 17% and 26%, respectively, with 16% surgical and 24% nonsurgical complications, mainly pulmonary. Important parameters proved to be extensive resections such as extended total gastrectomy, intraoperative blood loss and general physical condition (ASA I/II 24%, ASA III 34%). Total gastrectomy can be performed even in geriatric patients (greater than 70 years), although these patients had a clearly higher morbidity rate (48% vs. 35%) after extended procedures, the mortality rate not being increased. The overall mortality rate was 3.5%. PMID- 1635520 TI - [Perianal infections in Crohn disease. Results of local surgical treatment in comparison with non-Crohn patients]. AB - In a prospective study the results of local surgery in perianal infections in patients with and without Crohn's disease were compared. In patients with Crohn's disease (CD) the abscesses and fistulas were more extensive and complicated than in patients without Crohn's disease (NCD). The source of infection was cryptoglandular in 81% (CD) resp. 100% (NCD). The wound healing in CD-patients was four weeks longer than in NCD patients. Abscesses or fistulas recurred in 6/18 (CD) resp. 1/25 (NCD). Partial incontinence occurred in 6/18 CD and 5/25 NCD. It is concluded that perianal infections can be treated successful in most of patients with Crohn's disease. PMID- 1635521 TI - [Recommendations for ambulatory diagnosis of sleep apnea]. PMID- 1635522 TI - [Cumulative manifestations of acute intermittent porphyria]. PMID- 1635523 TI - [Step-wise diagnosis in gastroenterology. Liver, bile, pancreas]. PMID- 1635524 TI - [Successful fibrinolytic therapy of early diagnosed coumarin necrosis]. PMID- 1635525 TI - [Recent findings in the field of pediatric ophthalmology]. PMID- 1635526 TI - [The long-term prognosis of anorexia nervosa: the evaluation of hospital treatment]. AB - The present study is the continuation of a previous programme performed by a mail or phone questionnaire. In this study 18 subjects with anorexia nervosa were submitted to a clinical semi-structured interview, and underwent a medical examination regarding eating habits and Rorschach tests. Clinical results seemed to be quite satisfactory (none died and 84% were greatly improved or had recovered clinically) whereas the psychopathologic aspects were less positive. The authors conclude that complete clinical evaluation can be considered the only safe approach for the understanding of the clinical course. PMID- 1635527 TI - [A sampling epidemiological study of infant health in relation to the type of feeding]. AB - An epidemiological study has been carried out an the scholastic population of L'Aquila (Abruzzo). This study had the aim of verifying possible correlations between feeding procedures and the outbreak of illnesses whose causes are unknown. The information was registered with the collaboration of the Medical Scholastic Service, in the period of May-June in 1988-1989, interviewing four hundred and seventy-seven mothers of students, the information regards the temporary period of 1973-1985. The results of their elaboration are as follows: 75.9% of babies took breast milk at birth and in following months breast feeding was the most frequent (34.8%). The procedure breast feeding-bottle feeding was carried out in 30.4% of cases and exclusively bottle feeding in 22.4%. The study has permitted to discover thirteen cases of illnesses whose cause are unknown among which a case of SIDS (sudden infant death syndrome) in a newborn baby fed till eighteen weeks with breast milk and through twenty days before dying with undiluted cows milk. These illnesses happened in 13.4% of babies fed by bottle milk and diluted with running water; in 7.7% by cow's milk diluted with running water and in 4.3% by undiluted cow milk. Some Authors have suspected a relationship between bacterial endotoxin introduced by diet and baby illnesses whose causes are unknown. For this a quantitative determination of such substances is necessary in baby diets. PMID- 1635528 TI - [The activities of a pediatric emergency department. The emergency problems]. AB - The authors reviewed records of admission at the Fist Ais-Emergency Service of "G. Gaslini" Children's Hospital, data referring both to in and outpatients. First of all we took into account epidemiological data analysing occurrence and types of diseases; at the same time a demographic study, which aimed to show a decrease in the child population in Genova, was performed. Secondly we compared these data with the real number of admitted patients: collected data showed that this service has been used excessively. PMID- 1635529 TI - [Weight gain in the first 2 months of life in neonates with a birth weight less than or equal to 1500 g. A comparison between parenteral nutrition and orogastric feeding]. AB - This study was designed to verify the effectiveness of parenteral nutrition (NP) and continuous nasogastric feeding (AOG) in providing a good caloric intake and a good growth in the very low birth weight infants during the first 60 days of life. The study included 108 preterm babies with birth weight less than or equal to 1500 g: 26 received parenteral nutrition, 82 nasogastric feeding. Infants in NP showed a smaller postnatal weight loss and regained birth weight earlier than the AOG group. Caloric intake greater than 120 kcal/kg/die was achieved in 10.2 days of life in the NP group and in 14.1 days in the AOG group. Full enteral feeding was achieved later in the NP than in the AOG group (25.7 days vs 20.7 days). Weight gain at 60 days of life was better in the NP group (23.2 g/die vs 18.2 g/die), while there was no difference in the head circumference gain. The study shows the efficacy of NP in providing a good caloric intake in the very low birth weight infants in the first weeks of life. PMID- 1635530 TI - [Nutritional studies in a commune of Lazio. Anthropometric data and food consumption in childhood]. AB - The present study concerns with anthropometric and nutritional data collected in the school population of a small rural town in Lazio. We studied 368 school children of both sexes, belonging to the following age groups: from 7 to 8 years, 9 to 10 years, 11 to 12 years, 13 to 14 years. The technique of evaluation of obesity used in this paper is: weight 20% higher than the height-adjusted figure according to NCHS's curves and triceps skinfold higher than 90 degrees centile according to Tanner's curves. Dietary intake was assessed by a "24 hour-recall" on three consecutive days one of which of holiday. The prevalence of obesity is 17.7%. In all the age groups daily caloric intake is adjusted to that recommended by Italian 1987 Larn. On the other hand the single nutrient's assumption shows important differences from Larn. Particularly in all the age groups daily protein intake is high (14.6%-15.8% of the energy in a day), with an increased animal vegetable protein ratio (1.5-2.1). Dietary lipids are higher than 35.9% of day's energy (35.9%-39.5%); the polyunsaturated/saturated fatty acids ratio is low (0.3 0.5). Cholesterol in the diet (231-347 mg/day) exceeds the level recommended. The daily intake of total carbohydrates (45.3%-48.5%) is low. Crude fiber intake increases with age from 2.8 g to 4.5 g/day. There is no statistical difference between obese and not obese subjects for what concerns energy intake or single nutrient's assumption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635531 TI - [A rare case of idiopathic staghorn urolithiasis in childhood. Imaging diagnosis]. AB - The authors describe one case of kidney staghorn lithiasis in a little patient 1 1/2 years old, as complication of a megacalycosis with associated pyelo-ureteral junction dysplasia. They underline the value of ultrasound both as a first examination and, particularly, in the follow up because of the non invasivity of the technique and the correct information about the persistence of calculi and dilatation. PMID- 1635532 TI - [Cardiac rhabdomyoma in tuberous sclerosis. A report of five cases and review of the literature]. AB - Five children with tuberous sclerosis (TS), a polysystemic disease, had cardiac tumors detected by B-mode echocardiography. In a fetus, sonography performed at the eighth month showed the presence of a cardiac mass and of polycystic kidneys: the diagnosis of TS was confirmed postnatally because of the presence of calcified cerebral nodules. A newborn dichorial twin had paroxysmal tachycardia at ten days. B-mode echocardiography showed the presence of seven intracardiac tumors, and cerebral CT the presence of multifocal periventricular calcifications. An absence in a nine month old baby prompted an electrocardiogram that proved abnormal; a B-mode echocardiography showed large apical cardiac tumor; again cerebral CT showed periventricular calcified nodules. Two girls, 9 and 10 y.o. respectively, affected by TS, with normal electrocardiograms, both presented a small, asymptomatic, intracardiac mass demonstrated sonographically. In recent years, prenatal sonography and B-mode echocardiography in patients with TS demonstrated with increasing frequency the association of cardiac tumors (rhabdomyomas) with TS. Tumor detection often precedes the appearance of the cutaneous and neurological signs typical of the disease. This paper emphasizes the role of echocardiography in detecting cardiac tumors, as an early sign for the diagnosis of tuberous sclerosis, and to depict the natural history of cardiac rhabdomyoma with its variable clinical presentation and prognosis. PMID- 1635533 TI - [The Fanconi-Bickel syndrome: one more case]. AB - The association of de Toni-Debre-Fanconi syndrome with alteration of galactose metabolism and glycogen hepatic storage, before further clarification, is defined as Fanconi-Bickel syndrome. The Authors present a case in which the alterations in galactose metabolism typically do not affect the enzymes responsible for galactosemia. In such patients a recognised enzymatic defect glycogenosis is not involved and glycogen storage in the liver can be a secondary phenomenon, which can increase, differing according to each subject. Liver biopsy to detect storage can be avoided when all the other diagnostic criteria are observed. PMID- 1635534 TI - [The effects of lactitol in the treatment of intestinal stasis in childhood]. AB - Thirty-nine children (18 males, 21 females) suffering from intestinal stasis were treated with lactitol or a reference drug (lactulose in crystalline form), according to a balanced randomization, for 15 days. The first group of children included 19 subjects treated with lactitol, the second group included 20 subjects treated with lactulose. The dosages of lactitol and lactulose were, respectively, of 150-350 mg/kg and of 150-300 mg/kg daily per os with a single administration in the morning. During the trial, the children did not take any concomitant drug. For each patient the tested parameters were: number of intestinal evacuations, consistency of stool and adverse reactions (abdominal swelling, abdominal pain, nausea, vomiting, meteorism) daily; routine laboratory tests at the beginning and at the end of the trials. The results showed that the subjects treated with lactitol have manifested, besides a proved therapeutic efficacy, a better tolerability and compliance than the subjects treated with lactulose. PMID- 1635535 TI - [The exercise test in cystic fibrosis: the usefulness and applicability of various methods]. PMID- 1635536 TI - Neurotoxicity of phenytoin administered to newborn mice on developing cerebellum. AB - To examine the neurotoxic effects of phenytoin (PHT) on cerebellar development, we administered 50 mg/kg PHT suspended in sesame oil orally to newborn Jcl:ICR mice once a day during postnatal days 2-14 and determined plasma PHT concentrations at designated intervals during the administration period. In the treated group, walking reflex and negative geotaxis were poorly developed on postnatal day 14. Pyknotic cells in the external granular layer (EGL) significantly increased and were prominent in the vermis area compared with controls on postnatal day 14. Plasma PHT levels were 34-36 micrograms/ml on the 3rd day of PHT treatment and approached a steady-state situation. Total brain weight, size of the cerebellum, and cerebellar weight were significantly reduced in the treated group on postnatal day 56. Accordingly, oral administration of PHT in the neonatal period induced neurotoxic damage on the developing cerebellum. PMID- 1635537 TI - The use of dose equivalency as a risk assessment index in behavioral neurotoxicology. AB - This article reports changes with graduated dosage of alcohol on a standardized set of cognitive and psychomotor performance tests and refers to the approach as dose equivalency. Subjects (N = 20) were tested until their performance was stable on 10 tests from a microcomputer test battery. After administration of sufficient alcohol to achieve .15 blood alcohol level (BAL), using breath as the independent variable, the descending branch of the BAL curve was followed by measuring performance at set levels of alcohol. A dose-response relationship was confirmed in all performance tests (p less than .01), and multiple regression was used to select performance subtests that maximally predicted alcohol level. Four subtests were combined into a linear composite that related well to alcohol levels above 0.05 BAL (shrunken R = .75), which was used in a power function to approximate the roughly linear relation above 0.05, as well as the clearly nonlinear function between 0.05 and zero. It is suggested that alcohol, a powerful central nervous system depressant, can be a useful metric in communicating risk in neurotoxicological research. PMID- 1635538 TI - Neurodevelopmental effect of aluminum in mice: fostering studies. AB - In order to determine sensitive periods for induction of neurodevelopmental effects of aluminum (Al), mice were fed either 25 (control) or 1000 (high Al) micrograms Al/g diet (as Al lactate) from conception through lactation and litters were fostered either within or between groups at birth. Birth parameters were not influenced by Al intake. Food intake and body weight were 10%-12% lower during lactation in dams fed the high Al diets. Both gestation and lactation high Al exposure led to growth retardation in offspring beginning on day 10 postnatal; combined gestation and lactation exposure led to the biggest weight differential at weaning (23%). For neurobehavioral measures obtained at weaning, forelimb grasp strength was influenced by gestation high Al exposure, whereas negative geotaxis was influenced by lactation exposure, and hindlimb grasp and temperature sensitivity were influenced by both gestation and lactation exposure. Pup liver and brain manganese (Mn) and liver iron (Fe) concentrations at weaning were lower after high Al lactation exposure than in controls. Pup brain and liver Al concentrations were similar among the groups. These data show that mice are susceptible to neurodevelopmental effects of high maternal dietary Al intake during both gestation and lactation, and that high maternal intake can result in altered essential trace element metabolism in the offspring. PMID- 1635539 TI - Effects of prenatal cocaine on behavioral responses to a cocaine challenge on postnatal day 11. AB - The purpose of this study was to investigate the effects of prenatal cocaine treatment on behavioral responsivity to a cocaine challenge on postnatal day (PD) 11. Timed-pregnant Sprague-Dawley rats were injected s.c. with 40 mg/kg/day of cocaine (20 mg/kg twice daily) from gestational day 11 to 20. Saline-control females received saline injections and were pair-fed to the cocaine-treated females, whereas untreated-control females were undisturbed and were fed ad lib. Litters were culled to eight pups on PD1 and fostered to normal lactating dams. On PD 11, subjects were given either saline or cocaine (1.25, 2.5, or 5.0 mg/kg s.c.) and then tested 15 min later for isolation-induced ultrasonic vocalizations and other behaviors. Prenatal cocaine-treated pups showed a reduced sensitivity to the stimulating effect of postnatal cocaine on wall climbing, which may reflect an underlying alteration in central dopaminergic and/or noradrenergic systems. Most of the other behaviors studied, including ultrasonic vocalizations, were unaffected by prenatal cocaine administration. However, one other notable finding was an increase in postnatal mortality among the cocaine-exposed pups. We hypothesize that prenatal cocaine treatment may alter pup behavior so as to produce abnormal maternal-offspring interactions and impaired development in some individuals. PMID- 1635540 TI - Development of neurons and synapses in ochratoxin A-induced microcephalic mice: a quantitative assessment of somatosensory cortex. AB - Ochratoxin A (a mycotoxin) is known to cause cell death in the developing brain of embryos 1-2 days after treatment. Microcephaly was observed with high frequency in mice by prenatal treatment with ochratoxin A. Using a stereological method, the numerical densities of neurons and synapses were investigated in the somatosensory cortex of 6-week-old microcephalic mice. The numerical density of neurons in ochratoxin A-treated mice represented a 39% increase compared to the control mice, but there was no difference in the numerical density of synapses. The somatosensory cortices of control mice had about 13,000 synapses per neuron, whereas ochratoxin A-treated mice had about 9,400 synapses per neuron. The deficits in synapse-to-neuron ratios seen in ochratoxin A-induced microcephalic brain seemed to result from a reduced dendritic growth. PMID- 1635541 TI - The use of repeated measures analyses in developmental toxicology studies. AB - In many toxicology studies, it is common to take the same measurements on an individual animal at several time points (e.g., body weight across days or weeks, activity levels either within a single test session or across days). Such repeated measures for both maternal and offspring endpoints routinely are incorporated into developmental toxicology studies to allow characterization of the profile of treatment-related effects over time. To permit a valid statistical analysis, repeated measures studies are characterized by: random assignment of treatment to experimental units, measurement of the variable(s) of interest at the same time points for all animals, and avoidance of systematic overlaying of treatment and potential response gradients. Assumptions for and advantages of the use of a repeated measures analysis of variance versus single-factor analyses at each time point are illustrated in two data sets from a rat perinatal and postnatal study. The variance-covariance structure of repeated measures designs dictates that adjustments are necessary to provide protection against inflated Type 1 error rates. Communication between statisticians and toxicologists which allow the implementation of such analyses can improve the interpretation of data resulting from repeated measures study designs. PMID- 1635542 TI - Principles and pitfalls in the analysis of prenatal treatment effects in multiparous species. AB - Developmental studies often assess the effect of treatment of the pregnant mother on offspring. The use of multiparous species such as rats and mice in such studies creates a special set of design and analysis problems. These arise for two reasons. First, the availability of many offspring per litter tempts the experimenter to inflate sample size by treating scores from several pups per litter as independent observations. Second, large litter size seldom makes it practical to measure exposure effects in all offspring of an exposed dam. Such studies commonly involve two-stage sampling: Drawing a random sample of dams for treatment, then drawing a second sample of pups per dam for neurobehavioral measurements. In this article, such sampling was modeled by two different simulations. The first, a standard Monte-Carlo approach, sampled from random normal distributions for litter mean and within-litter variability. The second simulation sampled without replacement from actual data on weight of all pups in a series of 39 nontreated rat litters. These mutually-supportive approaches demonstrate that litter effects, even over as few as three litters, are generally large and statistically meaningful. Consequently, statistical significance tests are sensitive to litter effects. Inflation of sample size by treating as few as 2 pups per litter as independent measurements can almost triple the nominal 0.05 alpha level. Furthermore, two-stage sampling increases the within-treatment error term and correspondingly reduces statistical power relative to one-stage sampling.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635543 TI - The teaming leader in nursing--trendsetter for the 1990s. PMID- 1635544 TI - Certification is formal recognition for RN's demonstrated competence. PMID- 1635545 TI - Trends in ischemic heart disease mortality--United States, 1980-1988. AB - In 1989, approximately 500,000 persons died from ischemic heart disease (IHD), the leading cause of death in the United States (1). This report summarizes an analysis by CDC to characterize trends in IHD mortality in the United States from 1980 through 1988 (the latest year for which data are available), and emphasizes comparisons by race and sex, region, and state. PMID- 1635546 TI - Pregnancy risks determined from birth certificate data--United States, 1989. AB - The 1989 revision of the "U.S. Standard Certificate of Live Birth" includes new items of information about medical and lifestyle risk factors related to pregnancy, birth, and method of delivery (1,2). This report presents data about three of these new items: maternal weight gain during pregnancy, smoking during pregnancy, and method of delivery. For this analysis, to allow for more in-depth comparisons, data were limited to the two largest racial groups (black and white) in the United States. PMID- 1635547 TI - Homicide surveillance--United States, 1979-1988. AB - From 1979 through 1988, 217,578 homicides occurred in the United States, an average of greater than 21,000 per year. Homicide rates during this 10-year period were about 1.5 times higher than the rates during the 1950s. The national homicide rate of 10.7/100,000 in 1980 was the highest ever recorded. Homicide occurs disproportionately among young adults. Among the 15- to 34-year age group, homicide is the fourth most common cause of death among white females, the third most common cause among white males, and the most common cause among both black females and black males. In 1988, nearly two-thirds (61%) of homicide victims were killed with a firearm, 75% of these with a handgun. More than half (52%) of homicide victims were killed by a family member or acquaintance, and about one third (35%) of homicides stemmed from a conflict not associated with another felony. The homicide mortality rate among young black males 15-24 years of age has risen 54% since 1985. Ninety-nine percent of the increase was accounted for by homicides in which the victim was killed with a firearm. The surveillance data summarized in this report should assist public health practitioners, researchers, and policymakers in addressing this important public health problem. PMID- 1635548 TI - Influenza--United States, 1989-90 and 1990-91 seasons. AB - During the 1989-90 influenza season, 98% of all influenza viruses isolated in the United States and reported to CDC were influenza A. Almost all those that were antigenically characterized were similar to influenza A/Shanghai/11/87(H3N2), a component of the 1989-90 influenza vaccine. Regional and widespread influenza activity began to be reported in late December 1989, peaked in mid-January 1990, and declined rapidly through early April 1990. Most of the outbreaks reported to CDC were among nursing-home residents. Considerable influenza-associated mortality was reflected in the percentage of deaths due to pneumonia and influenza (P&I) reported through the CDC 121 Cities Surveillance System from early January through early April. More than 80% of all reported P&I deaths were among persons greater than or equal to 65 years. In contrast to the predominance of influenza A during 1989-90, during the 1990-91 influenza season 86% of all influenza virus isolations reported were influenza B. Widespread influenza activity was reported from mid-January through April 1991, with regional activity extending into May. Outbreaks were reported primarily among schoolchildren, and no evidence of excess influenza-associated mortality was found. Almost all the influenza B isolates tested were related to influenza B/Yamagata/16/88, a component of the 1990-91 influenza vaccine, but were antigenically closer to B/Panama/45/90, a minor variant. PMID- 1635549 TI - Chancroid in the United States, 1981-1990: evidence for underreporting of cases. AB - Chancroid, a bacterial sexually transmitted disease (STD) characterized by genital ulceration, has reemerged in the United States during the last decade. From 1950 to 1980, cases were infrequently reported. After an epidemic in California in 1981, however, the numbers of cases increased, peaking in 1987 at 5,035. Despite a subsequent decline in numbers of reported cases to 4,223 in 1990, new areas continue to report outbreaks. Interpreting chancroid surveillance data is difficult because confirmatory culture media are not commercially available. In addition, states may not require that unconfirmed or even confirmed cases be reported. To determine if chancroid is more widely distributed than surveillance figures indicate, CDC contacted STD clinics in 115 health departments, located in 32 states, the District of Columbia, and Puerto Rico- areas chosen because they had reported five or more cases of chancroid in any single year during 1986-1990--to determine if cases might be occurring but not reported. Only 16 of the 115 clinics had culture media available for Haemophilus ducreyi, and only nine had laboratory facilities complete enough to definitively diagnose chancroid, syphilis, or genital herpes, the most common STDs characterized by genital ulcers. Five or more clinically likely cases occurring in 1990 were identified in 24 states, seven more than surveillance figures indicated. Surveillance can be improved if a) states utilize the definitions for chancroid cases adopted for use in 1990 and b) microbiology laboratories utilize enhanced diagnostic methods. PMID- 1635550 TI - Chemical modification and irreversible inhibition of striatal A2a adenosine receptors. AB - The ligand recognition site of A2a-adenosine receptors in rabbit striatal membranes was probed using non-site-directed labeling reagents and specific affinity labels. Exposure of membranes to diethylpyrocarbonate at a concentration of 2.5 mM, followed by washing, was found to inhibit the binding of [3H]CGS 21680 and [3H]xanthine amine congener to A2a receptors, by 86 and 30%, respectively. Protection from diethylpyrocarbonate inactivation by an adenosine receptor agonist, 5'-N-ethylcarboxamidoadenosine, and an antagonist, theophylline, suggested the presence of two histidyl residues on the receptor, one associated with agonist binding and the other with antagonist binding. Binding of [3H]CGS 21680 or [3H]xanthine amine congener was partially restored after incubation with 250 mM hydroxylamine, further supporting histidine as the modification site. Preincubation with disulfide-reactive reagents, dithiothreitol or sodium dithionite, at greater than 5 mM inhibited radioligand binding, indicating the presence of essential disulfide bridges in A2a receptors, whereas the concentration of mercaptoethanol required to inhibit binding was greater than 50 mM. A number of isothiocyanate-bearing affinity labels derived from the A2a selective agonist 2-[(2-aminoethylamino) carbonylethylphenylethylamino]-5'-N- ethylcarboxamidoadenosine (APEC) were synthesized and found to inhibit A2a receptor binding in rabbit and bovine striatal membranes. Binding to rabbit A1 receptors was not inhibited. Preincubation with the affinity label 4 isothiocyanatophenylaminothiocarbonyl-APEC (100 nM) diminished the Bmax for [3H]CGS 21680 binding by 71%, and the Kd was unaffected, suggesting a direct modification of the ligand binding site. Reversal of 4 isothiocyanatophenylaminothiocarbonyl-APEC inhibition of [3H]CGS 21680 binding with hydroxylamine suggested that the site of modification by the isothiocyanate is a cysteine residue. A bromoacetyl derivative of APEC was ineffective as an affinity label at submicromolar concentrations. PMID- 1635551 TI - Tunicamycin increases desensitization of junctional and extrajunctional acetylcholine receptors expressed in Xenopus oocytes by a mechanism independent of N-glycosylation blocking. AB - Extrajunctional and junctional mouse muscle acetylcholine receptors (AChRs) expressed in Xenopus oocytes in the presence of tunicamycin desensitized more rapidly than the corresponding AChRs synthesized in the absence of tunicamycin. The two types of AChR expressed in non-tunicamycin-treated oocytes could be distinguished by their different rates of desensitization, but tunicamycin diminished this difference. The effect of tunicamycin on the AChR desensitization appeared to be reversible, and coapplication of tunicamycin with acetylcholine (ACh) also caused a similar effect on desensitization of these AChRs suggesting that the effect of tunicamycin was mediated by a mechanism independent of N glycosylation blocking. In addition, tunicamycin increased the amplitude of membrane current elicited by application of lower doses of ACh and accelerated the rate of desensitization, which suggests that tunicamycin favors an open channel state and, therefore, accelerates transition towards a desensitized state. Tunicamycin also increased the membrane current decay elicited by ACh in oocytes expressing incomplete AChRs, missing the beta, gamma, epsilon, or delta subunits. PMID- 1635552 TI - Staurosporine-induced neurite outgrowth in PC12 cells is independent of protein kinase C inhibition. AB - The protein kinase C (PKC) inhibitor staurosporine, a member of the K252a family of fungal alkaloids that are known as protein kinase inhibitors, induces neurite outgrowth in pheochromocytoma PC12 cells. The progressive staurosporine-induced neurotropic effect (EC50 = 50 nM) has the following characteristics: it is evident after 4 hr of incubation, requires the continuous presence of staurosporine, occurs at 37 degrees but not at 4 degrees, and is not blocked by K252a derivatives. Scanning electron micrographs showed long neurites, ruffling, and dense networks in nerve growth factor (NGF)-treated cells and short neurites, flattening, and smooth cell surface in staurosporine-treated cells. [3H]Staurosporine binding, which was time, temperature, and dose dependent, saturated at 5-10 nM. Other kinase inhibitors were poor competitors. The [3H]staurosporine bound over 20 hr at 37 degrees was poorly dissociated by acetic acid wash or unlabeled staurosporine. These results suggest an uptake process occurring at 37 degrees that is required for the neurotropic effect of staurosporine. NGF did not interfere with staurosporine binding, and staurosporine did not affect NGF receptor binding. At neurotropic concentrations of staurosporine, PKC in PC12 cells was completely inhibited. When PKC activity was down-regulated by prolonged exposure to phorbol myristate acetate, PC12 cells responded to staurosporine with neurite outgrowth similar to that of untreated cells. Although the target and mechanism of the neurotropic effects of staurosporine remain to be determined, the observed effects on PKC-deficient cells indicate that PKC may not be required for the neurotropic effect of this compound in PC12 cells. These results suggest that caution should be taken in the interpretation of staurosporine action in vivo, and they provide a pharmacological tool for the development of potential neurotropic drugs. PMID- 1635553 TI - Molecular neurotoxicology of trimethyltin: identification of stannin, a novel protein expressed in trimethyltin-sensitive cells. AB - The molecular basis of selective vulnerability of specific neuronal populations to neurotoxicants remains a key focus in neurotoxicology. Trimethyltin (TMT) selectively damages neurons in rodent and human central nervous system after a single exposure. By coupling subtractive hybridization with molecular cloning techniques, we isolated a cDNA specifically localized in TMT-sensitive cells. This 2.9-kilobase cDNA encodes a putative 10-kDa peptide of 88 amino acids, termed "stannin." In immunocytochemical experiments, antisera raised against the amino terminus of stannin exhibited strong immunoreactivity in TMT-sensitive neurons in the hippocampus and entorhinal cortex, areas previously identified by in situ hybridization. Northern blot and in situ hybridization experiments detected a 3.0-kilobase stannin mRNA in brain, spleen, and kidney; expression occurred as early as embryonic day 15 in rat brain and thymus. In situ hybridization in human hippocampus demonstrated a stannin mRNA in pyramidal and dentate gyrus neurons. High stringency Southern blot analysis of genomic DNA identified stannin homologs in rabbit, Drosophila, and human. These findings indicate that stannin is present in TMT-sensitive cells and may play a role in the selective toxicity of organotin compounds. PMID- 1635554 TI - Gender-related expression of rat microsomal epoxide hydrolase during maturation: post-transcriptional regulation. AB - Expression of microsomal epoxide hydrolase (mEH), levels of mEH mRNA, and the rate of mEH mRNA transcription were examined in hepatic and renal tissues at 4, 24, 44, and 56 weeks of age in male and 4, 14, 24, 34, and 44 weeks of age in female Sprague-Dawley rats. Immunoblot analyses revealed that hepatic mEH levels in males increased in an age-dependent manner, with a maximal increase (approximately 3-fold) being noted at 44 weeks of age, whereas the expression of hepatic mEH in females decreased significantly at 14 weeks of age or older, by approximately 70%s, compared with that of 4-week-old rats. Microsomes from kidney tissue failed to exhibit an age-dependent change in either sex. mEH mRNA levels were measured in total and poly(A)+ RNA isolated from hepatic and renal tissues. RNA blot hybridization analyses, probed with a 1.3-kilobase mEH cDNA, revealed that the levels of hepatic mEH mRNA in total RNA isolated from males were elevated approximately 1.5-, 2.8-, and 2.3-fold at 24, 44, and 56 weeks of age, respectively, relative to those at 4 weeks of age, whereas the levels of hepatic mEH mRNA in poly(A)+ RNA from males failed to change in an age-dependent manner. In contrast, the levels of hepatic mEH mRNA in either total or poly(A)+ RNA from female animals were dramatically decreased from 4 to 14 weeks of age, by approximately 90%. The suppressed levels of mEH mRNA in females were maintained at 24, 34, and 44 weeks of age (approximately 80%). However, the levels of renal mEH mRNA failed to change in an age-dependent manner in either sex, which was consistent with there being no change in the levels of mEH protein in kidney. In order to examine whether the gender-related maturational changes in hepatic mEH mRNA levels could result from transcriptional regulation, nuclear run-on assays were performed. The rate of hepatic mEH gene transcription failed to change in either males or females at the ages that exhibited significant changes in both mRNA levels and protein expression, suggesting that transcriptional regulation is not associated with the gender-dependent modulation of mEH mRNA levels during maturation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1635555 TI - Affinity alkylation of hamster hepatic arylamine N-acetyltransferases: isolation of a modified cysteine residue. AB - N-Acetyltransferases (NATs) play key roles in the detoxification and/or bioactivation of arylamines, arylhydroxylamines, arylhydroxamic acids, and hydrazines in mammalian tissues. In the present study, two hamster hepatic NATs (NAT I and NAT II) were separated, and each was purified greater than 2000-fold by sequential ammonium sulfate fractionation, DEAE anion exchange chromatography, Sephadex G-75 gel filtration chromatography, aminoazobenzene-coupled affinity chromatography, and DEAE anion exchange high performance liquid chromatography. Both NAT I and NAT II were purified to near-homogeneity. The molecular masses of NAT I and NAT II were estimated to be 30.5 kDa and 32.6 kDa, respectively. 2 (Bromoacetylamino)fluorene (Br-AAF) and bromoacetanilide were synthesized and evaluated as affinity labels for NAT I and NAT II. Whereas Br-AAF was a highly selective inactivator of NAT II, bromoacetanilide inactivated both NAT I and NAT II in a similar fashion. Inactivation of NAT II by both Br-AAF and bromoacetanilide, and inactivation of NAT I by bromoacetanilide, followed pseudo first-order kinetics. Relative rate constants (k(obs)/[I]) for the two compounds indicate that Br-AAF is approximately 25 times more potent than bromoacetanilide as an inactivator of NAT II. Both acetylcoenzyme A (CoASAc) and 2 acetylaminofluorene protected NAT II from inactivation by Br-AAF, and CoASAc provided protection of both NAT I and NAT II activities from inactivation by bromoacetanilide, indicating that the inactivation by both bromoacetanilide and Br-AAF is active site directed. The irreversibility of the inactivation of NATs by Br-AAF and bromoacetanilide was demonstrated by the failure to recover transacetylase activities after gel filtration of enzyme preparations that had been preincubated with Br-AAF or bromoacetanilide. Preincubation of NAT II with CoASAc significantly reduced the incorporation of [14C]Br-AAF into the enzyme, providing further evidence that the labeling is active site directed. In addition, pretreatment of NAT II with N-ethylmaleimide completely prevented the labeling of NAT II with [14C]Br-AAF, which suggests that a cysteine thiol is the target nucleophile of Br-AAF. High performance liquid chromatography analysis of the hydrochloric acid hydrolysate of [14C]Br-AAF-labeled NAT II revealed that 70% of total radioactivity is associated with S-carboxymethyl-L-cysteine, indicating that Br-AAF reacts primarily with a cysteine residue at the active site. These studies provide direct evidence that hamster hepatic NAT II contains an essential cysteine residue at the active site, and they establish the potential utility of Br-AAF for determining amino acid sequences in the active site of hamster hepatic NAT II. PMID- 1635556 TI - Identification of amino acid residues of 5-lipoxygenase-activating protein essential for the binding of leukotriene biosynthesis inhibitors. AB - 5-Lipoxygenase-activating protein (FLAP) is specifically labeled by [125I]L 669,083 and [125I]L-691,678, photoaffinity analogues of two classes of potent leukotriene biosynthesis inhibitors. Because human FLAP contains only a single tryptophan residue at position 72 and two internal methionine residues at positions 89 and 125, we have used reagents that specifically cleave at these residues, in conjunction with antipeptide antisera, to localize the site of attachment of the photoaffinity ligands. Immunoprecipitation of specifically labeled peptide fragments after digestion of photoaffinity-labeled FLAP by iodosobenzoic acid at 72Trp demonstrates that the inhibitors bind to FLAP amino terminal to this residue. This finding is consistent with similar immunoprecipitation studies after digestion at methionine residues using cyanogen bromide. These findings localize the site of attachment of the inhibitors to a region of FLAP that includes the hydrophilic loop between the proposed first and second transmembrane regions. Based on these findings, site-directed mutagenesis of human FLAP was performed to define key amino acids involved in inhibitor binding. Using a radioligand binding assay, analysis of mutants of human FLAP expressed in COS-7 cells demonstrates that a number of residues in the amino terminal half of the first hydrophilic loop of the protein can be deleted without significantly affecting inhibitor binding. In contrast, no inhibitor binding was detectable with mutants in which amino acid residues in the carboxyl-terminal half of this loop were deleted. Furthermore, a point mutation of 62Asp to asparagine results in a mutant with dramatically reduced affinity for inhibitors. This loss of affinity was not displayed by a mutant in which 62Asp was mutated to a glutamate residue, suggesting that a negative charge associated with residue 62 may be critical for inhibitor binding. The roles that amino acid residues in the carboxyl-terminal half of the first hydrophilic loop of FLAP may play in the binding of leukotriene biosynthesis inhibitors are currently under investigation. PMID- 1635557 TI - A shuttle vector system for the investigation of immunoglobulin gene hypermutation: absence of enhanced mutability in intermediate B cell lines. AB - Somatic hypermutation focused to the rearranged V(D)J segment of the immunoglobulin (Ig) loci contributes substantially to antibody gene diversification. However, neither the precise B cell subset subject to hypermutation nor the molecular mechanism(s) involved is known. One model proposes that Ig segments may be uniquely susceptible to DNA nicking and subsequent error-prone repair during a specific B cell developmental stage. We describe an SV40-based shuttle vector system for testing such a model. Plasmids containing two distinct Ig segments juxtaposed to the supF marker gene have been passaged through cell lines representing intermediate stages of B cell development, rescued and screened for marker gene mutations. To date we have not demonstrated enhanced supF mutation in any cell line examined, irrespective of the adjacent Ig segment. Thus, these cell lines exhibit normal DNA repair mechanisms and no evidence of increased endonuclease activity on the Ig segments tested. The feasibility of this system will allow similar experiments using other Ig target sequences exposed to a broader range of B cells. PMID- 1635558 TI - Sequences of variable regions of a monoclonal antibody specific to the thyroid hormone, triiodo-L-thyronine. AB - We have determined the nucleotide sequences of the variable regions of H and L chains of a monoclonal antibody 98QQ that interacts with the thyroid hormone triiodo-L- thyronine with high affinity. Analysis of the nucleotide sequence of the light chain V region of 98QQ revealed that the VL sequence is 99% identical to Balb/c germline Vk 21-E sequence. That is an interesting finding with this high affinity anti-T3 antibody, since occurence of predominantly germline variable region sequences is observed in some autoantibodies to self antigens but not usually in high affinity IgG antibodies. The sequence analysis also revealed that the heavy chain variable region sequence of 98QQ is similar to a V region of an anti-DNA antibody (MRL DNA 22). Thus the sequence analysis of our anti-T3 mAb 98QQ has revealed some features of autoantibodies to self antigens. PMID- 1635559 TI - Synthesis and secretion of a functional antibody in a vaccinia virus expression system. AB - A humanized rat monoclonal antibody (Campath 1H) has been expressed in HeLa cells using recombinant vaccinia viruses. Heavy and light chain recombinant viruses were constructed separately and when grown independently produced proteins of the expected molecular weights. Expressed heavy chain was entirely intracellular but light chain was mainly excreted and processed. When cells were infected at high multiplicity with both heavy and light chain recombinants a proportion of the heavy chain was then found in the extracellular medium. This secreted heavy chain was shown to be associated with light chain as judged by co-electrophoresis in non-reducing SDS polyacrylamide gels and by co-purification on protein-A sepharose. The secreted heavy and light chain complexes were functionally active as an antibody, with activity comparable to authentic Campath 1H antibody as assessed by ELISA, T-cell binding and antigen binding assays. Production of antibody in this system was achieved in the absence of serum, which is an important consideration in the production of monoclonal antibodies (MAbs). The amount of antibody produced was 0.2-0.4 micrograms/10(6) cells without optimization of expression levels. The wide host cell range of vaccinia virus together with the recently developed methods for increasing expression levels make this an attractive candidate as a flexible general vehicle for producing MAbs. PMID- 1635560 TI - Isolation and sequence of a cDNA coding for the immunoglobulin mu chain of the sheep. AB - A sheep cDNA library was screened with a human C mu probe, and the complete nucleotide sequence of a 1923 nt cDNA was determined. It contains sequences corresponding to all the exons (VH, DH, JH, CH1, CH2, CH3 and CH4) characteristic of the immunoglobulin mu heavy chain regions. The deduced amino acid sequence shows a percentage of identical residues in the range 65-45% when compared with the mu chains of various species. The VH region of this clone is clearly related to a group of genes that includes mouse VH36-60 and VHQ52, human VH2, VH4 and VH6 gene families and Xenopus VHII gene families. The constant region shows an unusual repartition of cystein and proline residues at the beginning of the CH2 domain, that may result in a molecule with enhanced stability and reduced flexibility. PMID- 1635561 TI - Characterization of soman-binding antibodies raised against soman analogs. AB - The production of antibodies against the highly toxic organophosphorus compound soman (GD) has been undertaken. Monoclonal antibodies were raised against two structural analogs of soman which served as haptens for immunization. In these soman analogs the chemically active P-F bond of the soman molecule was substituted by a P-OH group (which is ionized to P-O- under physiological conditions) or a P-H bond, creating compounds which we have named GDOH and GDH, respectively. These soman analogs were linked to carrier proteins through a short linker extending from the pinacolyl group. Monoclonal antibodies were selected according to their ability to bind to the immunizing hapten, and their specificities were determined by competitive inhibition assays. Out of total of 103 anti-GDOH antibodies 22 bound soman, whereas no binding was achieved with 62 anti-GDH antibodies. The two groups of monoclonal antibodies differed also in their structural specificity as demonstrated by different reactivities against a variety of soman analogs and substituted derivatives. These studies indicate that in order to achieve further improvement in anti-soman reactivity with protective potential, other groups (which resemble the OH group) have to be substituted for the F atom in the soman molecule. PMID- 1635562 TI - Mitogen-induced human T cell proliferation is associated with increased expression of selected PKC genes. AB - The induction of T cell proliferation and differentiation into mature effector cells is dependent on two principal exogenous signals that are provided by the antigen or mitogen and IL2. The enzyme protein kinase C (PKC) has a major role in the antigen-receptor signalling pathway in T cells, but appears not to be involved in signalling via the IL2-receptor (IL2-R). Since both pathways trigger a series of sequentially coordinated transcriptional events in which numerous genes are activated, we tested whether a T cell mitogen acting via the TCR/CD3 complex, and IL2, affect the expression of the conventional, Ca(2+)-dependent, PKC genes (alpha, beta and gamma) in T cells. Stimulation of human peripheral blood lymphocytes or an enriched population of human T cells with phytohemagglutinin resulted in augmented mRNA levels of PKC alpha and PKC beta, but not PKC gamma-gene. The response peaked at 24-48 hr when a 3-5-fold increase was observed. Stimulation of IL2-R alpha-expressing T cells with human recombinant IL2 induced cell proliferation and transcription of the IL2-R alpha gene (greater than 100-fold), but did not change mRNA levels of PKC alpha or PKC beta genes. The results suggest that stimulation of human T cells with mitogens acting via the TCR/CD3 complex, that involve activation of PKC, is accompanied also by a late activation of selected PKC genes. By contrast, agonists such as IL2, that operate via a different signalling pathway, do not modify the expression of any of the known conventional PKC genes. PMID- 1635563 TI - Interaction of aglycosyl immunoglobulins with the IgG Fc transport receptor from neonatal rat gut: comparison of deglycosylation by tunicamycin treatment and genetic engineering. AB - The role of carbohydrate in the structure and function of immuno-globulin Fc regions has been studied using the interaction of a monoclonal mouse IgG2b anti NIP antibody with the IgG Fc transport receptor from neonatal rat gut. An aglycosyl variant of this immunoglobulin, in which site-directed mutagenesis had been used to eliminate the carbohydrate attachment site in the CH2 domain by changing Asn297 to Ala, was compared in this system to aglycosyl immunoglobulin prepared from immunoglobulin-secreting cells treated with tunicamycin to inhibit N-linked glycosylation. Loss of carbohydrate from the heavy chain was confirmed for both methods by Western blotting of the separated chains with Concanavalin A, and no significant differences in circular dichroism spectra were found between glycosylated and non-glycosylated mutants. Removal of carbohydrate by site directed mutagenesis had no effect on binding of the immunoglobulin to the Fc transport receptor (FcTR) in vitro or transport from the gut to blood in vivo. Short-term clearance from circulation and degradation by gut contents in vitro were similarly unaffected. Mutation of Glu235 to Leu, an alteration that allows binding to human monocyte Fc gamma RI, did not alter the interaction with FcTR. However, treatment of wild-type or aglycosyl mutant cells with tunicamycin resulted in immunoglobulin which was less stable, cleared more rapidly and was transported slightly less efficiently. These findings indicate that the binding site for the FcTR may be unique among Fc-binding ligands, and that tunicamycin treatment may cause alterations in the immunoglobulin molecule in addition to loss of N-linked carbohydrate. PMID- 1635564 TI - The immunochemistry of sandwich ELISAs--V. The capture antibody performance of polyclonal antibody-enriched fractions prepared by various methods. AB - Studies compare the performance of antibody-enriched serum fractions prepared by various methods, when adsorbed on polystyrene microtiter wells as capture antibodies (CAbs) and tested against multivalent antigens. The criteria of performance in the RIA used included antigen capture capacity (AgCC) and the nmol of functional capture sites per microtiter well (CAbt). Affinity purified polyclonal (pAb) and monoclonal antibodies (mAb) were employed as reference CAbs. AgCC was highest for enriched fractions prepared using caprylic acid and a high pressure SpG affinity column. The performance of capture antibodies is expressed by an equation which was empirically derived and experimentally tested; CAbt x AgCC/ng adsorbed IgG. In terms of this parameter, CAb-enriched fractions prepared with caprylic acid performed best. The data reported also provide insight into solid-phase ligand immunochemistry. Adsorbed polyclonal CAb performed with remarkable homogeneity in percent bound and in Scatchard plots. Values obtained for CAbt from Steward-Petty plots were directly correlated with the length of the LBR of log-log percent bound plots but indicated that less than 10% of the potential capture sites of polyclonal CAbs remained functional after adsorption; mAb showed a more serious loss of activity. The loss of CAbt was a general phenomenon for all preparations tested although relative to their antibody content, certain antibody-enriched fractions retained a higher proportion of CAbt than their affinity-purified counterparts. Comparative studies in which the activity of adsorbed mAb and pAb was compared to the same antibodies immobilized by a non-adsorptive procedure, indicated that adsorbed CAbs also express lower affinity. The studies we report offer a single parameter criterium for comparatively evaluating CAb performance while simultaneously revealing the need to develop immobilization procedures that can preserve CAbt and antibody affinity so that immunoassays with wide dynamic ranges and high AgCC can be developed without waste of antibody. PMID- 1635565 TI - Gastric-outlet obstruction induced by prostaglandin therapy in neonates. AB - BACKGROUND: An infusion of prostaglandin E1 is widely used to maintain patency of the ductus arteriosus in neonates with congenital heart disease. After gastric outlet obstruction was recognized in several infants who received prostaglandin E1, we studied the association between the drug and this complication. METHODS: We evaluated all neonates who received prostaglandin E1 in our hospital between October 1, 1989, and September 30, 1991, for clinical, radiologic, or pathological evidence of acute gastric-outlet obstruction. RESULTS: Of the 74 neonates evaluated, 65 had no signs of gastric obstruction and were considered normal; 5 had clinical and radiologic or pathological evidence of gastric obstruction consistent with the presence of antral mucosal hyperplasia. The remaining four neonates had clinical signs of gastric obstruction, but no radiologic or pathological examinations were performed. The 5 neonates with antral hyperplasia had received prostaglandin E1 for longer periods (mean [+/- SD] duration, 569 +/- 341 hours) than the 65 normal neonates (54 +/- 58 hours, P less than 0.001) or the 4 neonates with clinical signs of gastric obstruction (119 +/- 60 hours, P less than 0.05). The cumulative dose of prostaglandin E1 was higher in the neonates with antral hyperplasia (2982 +/- 1392 micrograms per kilogram of body weight) than in the normal neonates (279 +/- 270 micrograms per kilogram, P less than 0.001) or the neonates with signs of gastric obstruction (528 +/- 306 micrograms per kilogram, P less than 0.01). In two neonates with antral hyperplasia, the cessation of therapy lessened the gastric-outlet obstruction. CONCLUSIONS: The administration of prostaglandin E1 to neonates can cause gastric-outlet obstruction due to antral hyperplasia. Neonates who receive prostaglandin E1 at recommended doses for more than 120 hours should be closely monitored for evidence of antral hyperplasia. PMID- 1635566 TI - Treatment of metastatic malignant melanoma with dacarbazine plus tamoxifen. AB - BACKGROUND: Endocrine factors may affect the clinical course of malignant melanoma and the response to the treatment of this disease. The presence of estrogen receptors in melanomas has been suggested, and occasional responses to antiestrogen therapy have been reported. METHODS AND RESULTS: We randomly assigned 117 patients with metastatic malignant melanoma to treatment with dacarbazine alone or dacarbazine in combination with tamoxifen. The overall rate of response, measured objectively, was higher (28 percent vs. 12 percent, P = 0.03) and survival was longer (median, 48 vs. 29 weeks, P = 0.02) among the patients who received dacarbazine plus tamoxifen than among those who received dacarbazine alone. Among women, both the response rate (38 percent vs. 10 percent, P = 0.04) and the median survival (69 vs. 30 weeks, P = 0.008) were better with dacarbazine plus tamoxifen than with dacarbazine alone, whereas among men the differences were smaller and not statistically significant. Among the patients given dacarbazine alone, there were no significant differences between women and men in response rate (10 percent vs. 13 percent) or survival (30 vs. 27 weeks), whereas among those given dacarbazine plus tamoxifen, women had better outcomes, as indicated by both response rate (38 percent vs. 19 percent, P = 0.15) and survival (69 vs. 31 weeks, P = 0.02). When we analyzed the Quetelet body-mass index (the weight in kilograms divided by the square of the height in meters) as an indirect indicator of the levels of endogenous estrogens in postmenopausal women and in men, survival was not affected by the body-mass index in the group given dacarbazine alone, whereas in the group given dacarbazine plus tamoxifen, survival was longer among patients whose Quetelet index was above the median value than among those with a Quetelet index lower than the median value (60 vs. 26 weeks, P less than 0.001). CONCLUSIONS: In the treatment of metastatic malignant melanoma, dacarbazine plus tamoxifen is more effective than dacarbazine alone, as indicated by both the response rate and the median survival; the difference in efficacy is among women. PMID- 1635568 TI - The vector of the Lyme disease spirochete. PMID- 1635567 TI - Brief report: primary immunodeficiency caused by mutations in the gene encoding the CD3-gamma subunit of the T-lymphocyte receptor. PMID- 1635569 TI - Refractory hypertension. PMID- 1635570 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 34-1992. A 19-year-old man with progressive proximal muscle weakness, contractures, and cardiac abnormalities. PMID- 1635571 TI - Gastric-outlet obstruction in children. PMID- 1635572 TI - Disseminated melanoma--is there a new standard therapy? PMID- 1635573 TI - Is a tick's bark worse than its bite? Formulating an answer with decision analysis. PMID- 1635574 TI - HIV-1 from a seronegative transplant donor. PMID- 1635575 TI - Suppressive therapy for cryptococcal meningitis. PMID- 1635576 TI - Suppressive therapy for cryptococcal meningitis. PMID- 1635577 TI - Suppressive therapy for cryptococcal meningitis. PMID- 1635578 TI - Surgical management of spastic diplegia. PMID- 1635579 TI - Intracranial hemorrhage in blacks as compared with whites. PMID- 1635580 TI - Intracranial hemorrhage in blacks as compared with whites. PMID- 1635581 TI - Changing blood types. PMID- 1635582 TI - Rhabdomyolysis with acute tubular necrosis--a nonglomerular cause of dysmorphic hematuria. PMID- 1635583 TI - Aerosolized recombinant human deoxyribonuclease I in the treatment of cystic fibrosis. PMID- 1635584 TI - An economic evaluation of asthma in the United States. PMID- 1635585 TI - Vaginal inflammation in Africa. PMID- 1635586 TI - A muscarinic receptor different from the M1, M2, M3 and M4 subtypes mediates the contraction of the rabbit iris sphincter. AB - In order to analyse the subtype of muscarinic receptors involved in the methacholine-induced contraction of the rabbit iris sphincter we have determined equilibrium dissociation constants (KB) of various antagonists in the sphincter muscle. The values were compared with those observed at M1 (rabbit vas deferens), M2 (heteroreceptors in rat iris) and M3 receptors (guinea-pig ileum), or at the muscarinic receptors in the guinea-pig uterus. The methacholine-induced contraction of the uterus from immature guinea-pigs was competitively antagonized by pirenzepine (6.64, -log KB), 4-DAMP (8.39), hexahydrodifenidol (HHD; 7.00 for the (R)- and 5.40 for the (S)-enantiomer), p-fluoro-hexahydrosiladifenidol (p-F HHSiD; 6.25) and valethamate bromide (8.04). The affinity of the antagonists is consistent with the presence of an M2 receptor. The -log KB values of the antagonists in the rabbit iris sphincter (6.43, p-F-HHSiD; 6.22, AQ-RA 741; 7.23 and 5.34, (R)- and (S)-trihexyphenidyl) were lower than, or within the lowest range of, estimates in the other experimental models, irrespective of the subtype selectivity of the antagonist. This excludes the presence of an M1, M2, M3 or M4 receptor in this smooth muscle. The affinity of UH-AH 37 in the iris was intermediate between that for M1 or M3, and M2 receptors. The low affinity of AQ RA 741 and the low enantiomeric ratio of trihexyphenidyl (THP) in the iris (77.6) would be compatible with a presumed M5 receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635587 TI - Presynaptic muscarinic receptor subtypes involved in the inhibition of acetylcholine and noradrenaline release in bovine cerebral arteries. AB - Experiments were performed in bovine cerebral arteries preincubated with [3H] choline or [3H]-noradrenaline to analyze the presynaptic muscarinic receptors involved in inhibition of acetylcholine and noradrenaline release induced by electrical stimulation (4 Hz, 200 mA, 0.3 ms, 1 min). For this purpose, the actions of several muscarinic receptor antagonists on the 3H overflow and on the carbachol-induced inhibition of this overflow were assessed. The evoked [3H] acetylcholine release and [3H]-noradrenaline release were markedly reduced by the presence of tetrodotoxin, Ca(2+)-free medium, and the inhibitor of both choline transport and choline acetyltransferase, AF64A. Chemical sympathetic denervation with 6-hydroxydopamine (6-OHDA) decreased the uptake of [3H]-noradrenaline, and AF64A reduced mainly the uptake of [3H]-choline, but also of [3H]-noradrenaline. Carbachol reduced the evoked [3H]-noradrenaline and [3H]-acetylcholine release; the IC50 values were 0.37 and 0.43 mumol/l, respectively. Atropine and 4-DAMP, but not AF-DX 116, methoctramine or pirenzepine, increased the evoked [3H] acetylcholine release. However, these muscarinic antagonists failed to modify the evoked [3H]-noradrenaline release. Carbachol inhibited the release of both acetylcholine and noradrenaline. The inhibition was blocked by the antagonists. The rank orders of potency (based on plC50 values) were, in the case of [3H] acetylcholine release, atropine greater than 4-DAMP greater than AF-DX 116 greater than or equal to pirenzepine greater than or equal to methoctramine, and, in the case of [3H]-noradrenaline release, atropine greater than 4-DAMP greater than AF-DX 116 greater than or equal to methoctramine greater than or equal to pirenzepine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635588 TI - Chronopharmacology of isoprenaline: the effects on rat plasma concentrations of large neutral amino acids depend on time of day for administration. AB - This investigation was undertaken in order to test our hypothesis, that the endogenous circadian rhythms in large neutral amino acids (LNAAs) in plasma are partly regulated by beta-adrenergic mechanisms. The beta-adrenoceptor agonist isoprenaline, which is known to decrease the concentrations of rat plasma LNAAs, was given at several time-points over a full 24-h period intraperitoneally to rats, which were killed 1 h later. Isoprenaline, administered in the evening, decreased the plasma amino acid concentrations more than it did in the same doses given in the morning. Also the potency of isoprenaline was in this respect higher in the evening than in the morning. This finding, of a time-of-day dependent relationship between the effects of a beta-adrenoceptor agonist and plasma LNAA concentrations, supports our hypothesis, that beta-adrenergic mechanisms are involved in the endogenous regulation of the plasma LNAA rhythms. We suggest that the known endogenous circadian variation in sympathetic activity, which gives rise to a reciprocal rhythm in beta-adrenoceptor responsiveness, could be one factor explaining that part of the circadian rhythm in plasma LNAA concentrations, which is not due to variations in food intake. PMID- 1635589 TI - Characterization of extracellular GABA in the substantia nigra reticulata by means of brain microdialysis. AB - Brain microdialysis was used to characterize extracellular gamma-aminobutyric acid (GABA) in the substantia nigra reticulata (SNR) of freely moving rats. The extracellular GABA in the SNR was characterized using acutely implanted probes (4 8 h after surgery; day 1) and chronically implanted probes (24 h after surgery; day 2). 3-Mercaptopropionic acid, a glutamic acid decarboxylase inhibitor, was used to identify GABA. This drug induced an immediate decrease in the extracellular GABA levels to 40% of basal values, suggesting that the detected GABA is, at least in part, newly synthesized. The basal levels of extracellular GABA measured either on day 1 or day 2 were not affected by infusion of micromolar amounts of tetrodotoxin. Therefore, a direct coupling between GABA dialysate concentrations and nerve-impulse flow does not seem to exist. Infusion of the GABA uptake inhibitor nipecotic acid (0.5 mmol/l) resulted in a 4-fold increase in the dialysate levels of GABA lasting at least for 3 h on both days. K+ stimulation (60 mmol/l) increased extracellular GABA levels in the SNR to 450% of basal values. This effect again did not differ significantly on day 1 and day 2. The origin of the extracellular GABA in the SNR, as recorded by microdialysis under the two experimental conditions, is discussed. PMID- 1635590 TI - Dopamine releasing effect of phenylbiguanide in rat striatal slices. AB - The present study explored the mechanisms underlying the dopamine releasing effect of phenylbiguanide, a compound commonly used as a 5-HT3 receptor agonist. Phenylbiguanide, and also serotonin and 2-methyl-serotonin, enhanced the outflow of radioactivity from superfused rat striatal slices preloaded with [3H]dopamine. The presence of the dopamine uptake blocker nomifensin prevented the increase in outflow. The effect of phenylbiguanide was not antagonized by 5-HT3 receptor antagonists, did not require the presence of Ca2+ in the superfusion buffer, and also occurred in reserpinized preparations with depleted dopamine stores. Phenylbiguanide caused a greater shift in the distribution of superfusate radioactivity from DOPAC to dopamine than did nomifensin. All these results are in agreement with an exchange mechanism by which phenylbiguanide promotes the efflux of dopamine by operation of the uptake carrier in the reversed direction. In consonance, phenylbiguanide, and also serotonin and 2-methyl-serotonin, inhibited the binding of [3H]CFT to dopamine uptake sites, although the rank order for promoting outflow, serotonin greater than phenylbiguanide greater than 2-methyl-serotonin, differed from that for inhibiting [3H]CFT binding to dopamine uptake sites, 2-methylserotonin approximately serotonin greater than phenylbiguanide. The present results raised the possibility that phenylbiguanide has an additional activity in releasing vesicular dopamine into the cytoplasmic pool. PMID- 1635592 TI - [Food as cause of atopic eczema in children]. PMID- 1635591 TI - Antihypertensive activity of the non-peptide angiotensin II receptor antagonist, SK&F 108566, in rats and dogs. AB - The antihypertensive activity of the nonpeptide angiotensin II receptor antagonist, SK&F 108566 (E)-alpha-[[2-butyl-1-[(4-carboxyphenyl)methyl]-1H imidazol-5- yl]methylene]-2-thiophene propanoic acid), was examined in rats and dogs. SK&F 108566 produced dose-dependent decreases in blood pressure in renin dependent hypertensive rats. At 10 mg/kg intraduodenally, mean arterial blood pressure fell from between 150-160 mm Hg to approximately 124 mm Hg. A sustained infusion of SK&F 108566 at 25 micrograms/min intraduodenally normalized blood pressure during 3 days of infusion and for 18 h following cessation of the infusion. Evaluation of the systemic hemodynamic effects of SK&F 108566 in chronically instrumented renin-dependent hypertensive rats demonstrated that the antihypertensive effects of SK&F 108566 were accompanied by a significant increase in cardiac output with little change in stroke volume. In dogs made acutely hypertensive by an intravenous infusion of angiotensin I, SK&F 108566 resulted in dose-dependent decreases in blood pressure. The antihypertensive activity of SK&F 108566 at 10 mg/kg p.o. was maintained for between 13-15 h, a similar duration of action as observed with enalapril (1 mg/kg, p.o.). Administration of DuP 753 (losartan) intravenously caused a small and short-lived fall in blood pressure in the angiotensin I-infused hypertensive dog. However, the active metabolite of losartan, EXP 3174, resulted in a response of longer duration. In dogs made hypertensive by placement of an ameroid constrictor on the left renal artery, SK&F 108566 (10 mg/kg, p.o.) or enalapril (1 mg/kg, p.o.) resulted in antihypertensive responses of at least 12 h duration. The data indicate that SK&F 108566 is a long-acting antihypertensive agent in the rat and dog. PMID- 1635593 TI - [Discontinuation of anonymity of donors in artificial insemination; a moral assessment of counter-arguments]. PMID- 1635594 TI - [AIDS, a problem without boundaries]. PMID- 1635595 TI - [Estrogen substitution following the menopause and the risk of breast cancer; the importance of endogenous risk factors]. PMID- 1635596 TI - [Epiphysiolysis of the femoral head]. PMID- 1635597 TI - [Current possibilities in the treatment of severe stenosis of the large airways]. PMID- 1635598 TI - [Immunologically mediated contact urticaria caused by foods in young children with constitutional eczema]. AB - Fifty-two children with atopic dermatitis were investigated with the mixed-food radio-allergosorbent test (RAST) and the skin provocation test 'Skin Application Food Test' (SAFT). The mixed-food RAST is a commercially available test with multiple allergens on one disk. The disk contains 6 common food allergens: cow's milk, egg, peanut, soy, codfish and wheat. The SAFT is a system with which foods are applied to the skin in the state in which they are consumed. This test system is routinely used in our subdivision of Paediatric Dermatology in Sophia Children's Hospital. In some children, atopic dermatitis grew worse after a positive SAFT reaction. In 50% of the 38 children with food allergy a correlation was found between exacerbation/induction of atopic dermatitis and consumption or direct skin contact of foods to which the child was allergic. Due to direct skin contact of foods, atopic dermatitis can grow worse with sudden attacks of pruritus, especially on the hands and in the face. The SAFT imitates the naturally occurring symptoms, is child friendly and easy to perform. The mixed food RAST can be used as a screening test to identify the children with atopic dermatitis and an atopic immune response to foods, so possibly food allergy. Further investigations of the sensitivity of the target organ (in atopic dermatitis: the skin) and the usefulness of the SAFT are then indicated. PMID- 1635599 TI - [Prevalence of putative food hypersensitivity in young children]. AB - Prevalence, symptoms and family prevalence of food hypersensitivity and other hypersensitivities were investigated in a group of 5-6-year old children (n = 1039) in a rural area of the Netherlands using a questionnaire for the parents. Subsequently parents were asked about their actions once they suspected their child of food hypersensitivity. According to 23.1% of the parents their child was hypersensitive, and mostly food hypersensitive (11.4%). In particular, gastrointestinal symptoms, crying spells in infancy and behaviour problems were reported. These symptoms were usually caused by cows' milk, food additives and chocolate. Most of the food hypersensitive children experienced their first problems before their first birthday. Although only 39% of these children were examined, 91.5% of the parents of the so-called food hypersensitive children restricted the food intake of their children. CONCLUSION: Many parents consider their children to be food hypersensitive and they restrict the food intake without any examination. PMID- 1635600 TI - [Routine screening for syphilis in neurology is not useful]. AB - In a retrospective study the results of the screening for syphilis in one of the neurological wards of the Academic Medical Centre in Amsterdam were analysed. The Venereal Disease Research Laboratory test (VDRL) and the Treponema Pallidum Haemagglutination Assay (TPHA) in serum were used for screening. The data for analysis were obtained via the hospital computer data base and via the medical files of the department of neurology. During the 5-year study period (1986-1990) 2378 adult patients were admitted and 1247 (52.4%) of them were screened. In seven (0.56%) patients both tests were positive. Three of them had been treated for syphilis in the past and showed no symptoms of active syphilis. Four (0.32%) patients suffered from active neurosyphilis. In three of these four patients syphilis was suspected on admission and confirmed by the tests. In one patient the diagnosis of syphilis was not considered. The positive test results became available shortly before she died of pneumonia and were without consequences. None of the 32 (2.6%) patients with a positive TPHA and a negative VDRL was diagnosed as having (neuro-)syphilis. Two (0.16%) patients had a false-positive VDRL. We conclude that routine serological examination for syphilis of every patient admitted to a neurological ward is not useful. We advise a limited screening of patients who belong to a group with high risk for syphilis and patients with symptoms and signs that can be caused by syphilis, such as dementia or ischaemic strokes at a relatively young age. PMID- 1635601 TI - [Tungiasis]. AB - Tungiasis is an inflammation of the skin caused by infestation of a fertilised female sand flea, Tunga penetrans. Two patients who contracted this skin disease in the tropics (Surinam and Kenya-Uganda) are described. Because of the increase of international travelling, import diseases are seen more often. If the disease is known, it is easy to diagnose and to treat tungiasis. PMID- 1635603 TI - [Medical activities under adverse conditions. Study Group Medical Development Cooperation]. PMID- 1635602 TI - [Serious psychological side effect in children taking high doses of deptropine]. AB - Since 1986 the Netherlands Centre for Monitoring of Adverse Reactions to Drugs has received 16 reports concerning psychic effects attributed to the use of deptropine citrate (Brontine) in children ranging from one to ten years of age. Within 1 to 3 days after starting treatment with a daily dose of 0.6-3 mg, hallucinations appeared in 7 children, aggressive behaviour and/or agitation in 6 children, ataxia in 2 children, and anxiety in 1 child. In none of these cases could another cause be found. In one patient symptoms persisted during the whole 15-month period of treatment. All patients recovered rapidly after discontinuation of deptropine citrate. As it probably concerns a dose-dependent effect and because most patients had been prescribed a daily dose of 0.06 mg/kg body weight, it is strongly advised to exceed the recommended daily dose of 0.03 mg/kg body weight as little as possible. PMID- 1635604 TI - [The acute stage of cerebrovascular accident (CVA); characteristics and management]. PMID- 1635605 TI - [The value of proton spin resonance tomography in the diagnosis of intra articular pathological symptoms of the knee]. PMID- 1635606 TI - [Of what benefit is a research internship in the tropics for Dutch medical students?]. PMID- 1635607 TI - [Minor symptoms in family practice; keratitis due to ultraviolet rays]. PMID- 1635608 TI - The impact of caring on politics. PMID- 1635609 TI - A student's perspective. PMID- 1635610 TI - In response to April 8th release of Louis Harris poll on the public's attitudes about health care. PMID- 1635611 TI - Human animal interaction: basis fo pet-therapy. PMID- 1635612 TI - Workplace advocacy survey. PMID- 1635613 TI - [Diagnosis and therapy of meningosis neoplastica]. AB - Metastatic leptomeningeal disease occurs in 5-30% of patients with breast or lung cancer, malignant melanoma, non-Hodgkin's lymphoma, leukemia and primary malignant brain tumors. Intrathecal chemotherapy with methotrexate, cytarabine, or thiotepa combined with irradiation of the site of major involvement increases overall median survival from 1-2 months to 2-7 months. Clinical outcome is limited by progression of systemic or CNS disease and by the neurotoxic side effects of therapy, i.e. leukoencephalopathy. New immunotherapeutic strategies of intrathecal treatment may be effective and less toxic, but are not yet sufficiently defined and available. This review covers the current diagnostic and therapeutic features of metastatic leptomeningeal disease. Pragmatic therapeutic recommendations, based on available clinical knowledge are given with special consideration of the side effects of therapy. PMID- 1635614 TI - [Examination of the visual system with transcranial magnetic stimulation]. AB - The influence of transcranially applied magnetic stimuli on the function of the afferent (sensory) and efferent (motor) parts of the visual system have been discussed. Excitatory (positive) phenomena are subjective photic sensations (phosphenes) which can be elicited by transcranial magnetic stimulation over occipital parts of the skull. The phosphenes appear on the left or right side of the visual field depending upon the direction of the coil currents, which determines whether the visual cortex of the right or the left hemisphere is activated. The configuration of the phosphene fields hints at an excitation of the primary visual cortex (Brodmann's area 17). However, magnetic brain stimulation also produces inhibitory (negative) phenomena. When strong magnetic field pulses are applied over the primary visual cortex, foveally presented visual stimuli cannot be identified even when no phosphenes are perceived at the same time. Depending on the position of the stimulation coil, this suppression of perception can be restricted to visual stimuli presented on the right, or left of, above or below the fixation point. No generation or disturbance of eye movements by transcranial magnetic stimulation has been reported before, except for a delay of saccades within a reaction time paradigm. PMID- 1635615 TI - [Fibromuscular dysplasia as a cause of cerebral infarct]. AB - Fibromuscular dysplasia (FMD) is a non-atheromatous, non-inflammatory, segmental arteriopathy of unknown etiology. Fibroplasia of the tunica media is most common. After the renal arteries, the carotid arteries are most frequently affected. Angiographically beaded and tubular stenoses are seen. Complete occlusions and spontaneous dissection of the carotid arteries occur. The angiopathy causes general symptoms such as headache and vertigo, but also recurrent TIA and ischemic cerebral infarction. We examined 15 patients (12 female) suffering from FMD and stroke. The diagnosis of FMD was based on angiographic findings in all cases. 13 patients made a good recovery and seven of them could be discharged from hospital without any neurological deficit. Apart from conservative treatment, primary percutaneous or operative angioplasty may be necessary in some cases in spite of the mostly benign outcome of the disease. Acetylsalicylic acid should be given in all cases. PMID- 1635616 TI - [Vertebrobasilar ischemia. Value of Doppler ultrasound in the acute phase]. AB - We prospectively studied patients with acute vertebrobasilar ischaemia to assess the value of Doppler ultrasound compared to cerebral angiography during initial evaluation. Doppler ultrasound was diagnostic in 11 of 14 patients (79%). Transcranial ultrasonic examination yielded important information in addition to extracranial findings in 8 of 11 patients. Depending on the underlying vascular pathology, Doppler ultrasound proved to be a useful screening instrument to support acute management of vertebrobasilar ischaemia. With regard to clinical symptoms and ultrasonic findings, practical consequences for diagnostic evaluation are proposed. PMID- 1635617 TI - [Transcranial Doppler ultrasound in carotid endarterectomy]. PMID- 1635618 TI - [Neuro-Behcet's syndrome: encephalitis and cerebral venous thrombosis--clinical aspects and neuroradiology of 5 cases]. AB - The value of brain CT-scan, magnetic resonance imaging (MRI) and angiography for diagnosis, differential diagnosis and follow up in Neuro-Behcet-Syndrome is assessed in 5 cases. Three of the patients presented with clinical signs of encephalitis. Further investigations led to the diagnosis of Behcet-Syndrome. CT scan was negative in two of these cases, but MRI showed multiple, predominantly periventricular lesions with high signal intensity on T2-weighted spin-echo images in all three. Clinical symptoms improved with steroid and chlorambucil therapy in all three cases. In two patients the MRI-lesions resolved at least partially after 1.5 and 3 years of treatment respectively. In one patient the initial MRI-findings were still present after 7 months of treatment. The other two patients presented with headache, papilledema and increased CSF-pressure. The cause was superior sagittal sinus thrombosis, confirmed by angiography in both cases. Additional symptoms appeared later and led to the diagnosis of Behcet syndrome. One patient died of pulmonary aneurysms 28 months after the diagnosis had been established. The course of disease of the remaining patient is so far favorable. PMID- 1635619 TI - [Spontaneous regression of significant stenoses and occlusions of the internal carotid artery]. AB - 19 patients with severe stenoses or occlusions of the internal carotid artery showed spontaneous recanalization at follow-up. The cause of the stenotic process was spontaneous or traumatic dissection, fibromuscular dysplasia, ergotism or arteriosclerotic disease. Total recanalization occurred in carotid artery dissections coinciding with the best clinical outcome. In fibromuscular dysplasia and arteriosclerotic process, recanalization was seldom found, incomplete, and the clinical course was less favourable. PMID- 1635620 TI - [Lack of specificity of single photon emission computerized tomography in dementia--results of a case of progressive paralysis]. AB - In a 53-year old male suffering from paretic neurosyphilis, SPECT-investigations were performed before and after treatment with high doses of Penicillin G. The patient was admitted for disturbances of speech and concentration, memory disorder and tonic-clonic seizures. Mental examination showed a mild dysphoria and irritability in mood, but no disturbance of orientation, no euphoria or expansive delusions, and no paranoia. Mini-Mental-State examination was within the normal range (28 points); no abnormalities were found on neurologic examination, and CT and MRI investigations showed normal findings. The diagnosis was verified by CSF-examination (pleocytosis, elevated protein, positive Lues reactions). SPECT investigation with Tc 99m HMPAO (20 mCi, single-head rotating camera) revealed a pronounced bilateral parieto-temporal uptake deficiency as observed in patients with dementia of Alzheimer's type. After 18 months the clinical symptoms had remitted, and laboratory findings were improved. On the other hand, the bilateral parieto-temporal uptake deficiency in SPECT remained unchanged. Possible causes of these findings are discussed in relation to neuropathologic findings. It can be concluded that bilateral parieto-temporal uptake deficiency in SPECT is a nonspecific finding and that there is no correlation between clinical improvement and SPECT pattern in paretic neurosyphilis. PMID- 1635621 TI - [Hemodynamic monitoring during a migraine attack with aura. A case report]. PMID- 1635622 TI - [Communicating syringomyelia and syringobulbia after surgery of a spinal epidural tuberculoma]. AB - In a 46 year old patient a syringomyelia and syringobulbia were diagnosed clinically 18 years after a transverse lesion of the cord and removal of an epidural spinal tuberculoma. Post-myelographic CT and NMR scans showed a communicating syringomyelia and syringobulbia. A flavectomy was performed and a syringopleural shunt implanted. The operation was successful by neuroradiological criteria. Clinically there was a worsening of the spastic gait during one-year follow up. Neuroradiological findings and etiology of the syrinx are discussed, and a causal relationship to the tuberculoma is proposed. PMID- 1635623 TI - CT-stereotactic fibrinolysis of spontaneous intracerebral hematomas. AB - CT-stereotactic fibrinolysis is an effective alternative to surgical and conservative therapies for intracerebral hematoma. The method consists of stereotactically puncturing and partially evacuating the hematoma. After fibrinolysis using urokinase, the residual hematoma is completely evacuated through a catheter inserted in the cavity of the hematoma. The operation is usually performed under local anesthesia. Stereotactic methods are safer and less invasive than other methods. Since October 1985, a total of 85 patients have been treated with this method in the Department of Stereotaxy and Neuronuclear Medicine at the University of Freiburg Medical School. Although 25 patients died (29.4%) during the mean follow-up period of 20 months, only 16 (18.8%) died in the acute postoperative phase or within the first 60 days after evacuation. Eighteen patients (21.2%) had died six months after the operation. The quality of life of the 60 surviving patients, as measured on the Karnofsky Scale at follow up, was very good to good in 70% and moderate in 23.3%. Only 6.7% of the patients were so disabled that they required special care and assistance or had to be placed in a nursing home. The long-term results are thus very encouraging. PMID- 1635624 TI - Clinical and cerebral blood flow studies in patients with intracranial hemorrhage and amyloid angiopathy typical of Alzheimer's disease. AB - Spontaneous intracerebral hemorrhages can occur in patients with severe amyloid angiopathy and other morphological signs of Alzheimer's disease (AD). We observed 15 patients in whom histological examination of brain tissue specimens obtained at surgery revealed characteristic congophilic amyloid deposits in subcortical arteries and/or nerve cells. Clinical follow-up examinations were carried out up to 9 years after diagnosis. In addition, three survivors from the operated group were investigated by neuropsychological testing and single photon emission computer tomography (SPECT) using Tc-99m-HMPAO for determination of regional cerebral blood flow (rCBF). SPECT could not differentiate between the "typical Alzheimer disease pattern" of bilateral temporo-parietal rCBF reduction and flow deficits resulting from previous hemorrhage. Intellectual functioning was found to be impaired to various degrees ranging from normal function to severe dementia (MMS test scores varied between 15 and 26 points); again, it was difficult to differentiate clinically between the nosologic entities mentioned above. On the basis of our present experience we cannot distinguish between brain dysfunction due to Alzheimer's disease and intracranial hemorrhage from amyloid angiopathy. This supports the idea that intracranial hemorrhage may only be one clinical manifestation of amyloid deposits, another one being "Alzheimer's disease" with varying preponderance. PMID- 1635625 TI - Non-acoustic tumors of the cerebellopontine angle. AB - 52 patients with non-acoustic neurinoma tumors of the cerebellopontine angle undergoing surgery over a 16 year period (1974-1989) are analyzed with regard to epidemiologic factors, presenting symptoms, neurological findings, diagnostic procedures, surgical approaches, recurrences, and longterm survival rates. Meningiomas (20 cases) and epidermoid tumors (16 cases) outnumber the rare tumors which exhibit wide histological variation. Trigeminal neuralgia was found as a significantly frequent sign of epidermoids. Total removal was possible in nine meningiomas (45%), fourteen epidermoid tumors (87.5%) and 11 (69%) mostly malignant rare tumors. There were many longterm survivors in meningioma and epidermoid groups with a median follow-up period of 4.1 years. The results are compared to those reported in the literature and a brief review of reported rare tumors of the angle is presented. PMID- 1635626 TI - Intracranial cavernous angioma. AB - We report 14 cases of intracranial cavernous angioma, analyzing the clinical features, with special reference to the risk of bleeding, radiological images and treatment in these and in 153 published cases, 167 in all. Cerebral hemorrhage occurred in 44%: typical (intraparenchymal or subarachnoid) in 24.6%, and masked by epilepsy, headache or neurological deficits in 19.2%. In patients with the typical hemorrhagic pattern posthemorrhagic mortality was 12.2%. Of the patients who had a hemorrhage 42.5% were left with more or less disabling neurological deficits, and 16.4% had a rebleed. In discussing treatment we consider four groups of intracranial cavernous angioma: A) symptomatic in a zone of low surgical risk; B) asymptomatic with low surgical risk; C) symptomatic with high surgical risk; D) asymptomatic with high surgical risk. The treatment is surgical, except in the high risk asymptomatic variety, best followed initially with sequential CT scan and MRI and then considered for surgery if the lesion becomes symptomatic, increases in size or presents neuroradiological signs of bleeding. PMID- 1635627 TI - Intramedullary metastasis of unknown origin: a case report. AB - We report a case of cervicothoracic intramedullary metastasis with long survival. The patient is in satisfactory neurological condition 18 months after operation and has resumed her normal lifestyle. Despite meticulous examinations, the primary lesion could not be identified. We discuss the relevant published work. PMID- 1635629 TI - Achondroplasia: unusual bone abnormalities of the cervical spine. AB - We report the case of an achondroplastic child in whom severe morphological and postural abnormalities of the cervical vertebrae were coupled with only mild and stable neurological deficits. The pathogenesis of the abnormalities is discussed. PMID- 1635628 TI - A case of Foster Kennedy syndrome without frontal lobe or anterior cranial fossa involvement. AB - Foster Kennedy syndrome is a very rare syndrome which includes ipsilateral optic atrophy and central scotoma, anosmia, contralateral papilledema, and, occasionally, ipsilateral proptosis. A large frontal lobe, olfactory groove, or medial third sphenoidal wing tumor, usually a meningioma, creates this syndrome. In this report, the author presents a case of metastatic cerebral tumor with Foster Kennedy syndrome but without frontal lobe or anterior cranial fossa involvement. PMID- 1635630 TI - Meningioma of the fourth ventricle: a case report. AB - A rare case of fourth ventricle meningioma with a combined intraventricular intracerebellar localization, successfully removed by surgical treatment, is reported. The features of this type of meningioma as compared to the purely intra ventricular variety are discussed. PMID- 1635631 TI - Management and prognosis of intracranial giant aneurysms. A report on 58 cases. AB - Between 1975 and 1989, 58 patients, 32 females and 26 males, mean age 50 years, with intracranial giant aneurysms with a diameter more than 2.5 cm were treated at our clinic. 48% of the patients presented with subarachnoidal hemorrhage. The most of the other 30 patients presented with cranial nerve dysfunctions. The most common site of the aneurysm was the internal carotid artery (25 cases, 43%), followed by the anterior cerebral artery (14%), and the vertebro-basilar region (11 cases, 19%). In 14 patients direct surgery was not performed because of the poor general condition of the patient, the high risks, or non-consent. In seven patients (12%) the aneurysm had been misdiagnosed as meningeoma, pituitary adenoma, craniopharyngeoma or glioblastoma. 47% of all patients were discharged as "independent" and 19% died. Patients without SAH had better chance of survival: 7% of patients without SAH died and 29% of patients with hemorrhage. 50% of patients without hemorrhage were discharged as "independent" but only 18% of patients with SAH. Because of the high incidence of hemorrhage and the better prognosis for patients without hemorrhage, we recommend routine surgical treatment of patients with giant aneurysms. PMID- 1635632 TI - [From praxis to the concept of monitoring in anesthesia and intensive care]. PMID- 1635634 TI - [Temperature monitoring and sites of measurement of body temperature]. AB - The authors report an investigation of 331 consecutive patients submitted to major surgery to evaluate the reliability of temperature monitoring in different body sites in relation to central temperature. After having considered the minimal temperature changes and the difficulties due to the different techniques used, it is concluded that the measurement at the middle 3rd of the oesophagus is the most reasonable measurements site. PMID- 1635633 TI - [Clinical evaluation of pre-surgical anxiety: changes in plasma levels of the anxiety peptide (diazepam binding inhibitor)]. AB - The score scale of anxiety (STAI, Y, 1-2) and haematic levels of DBI (diazepam binding inhibitor) were used in 48 surgical patients for clinical evaluation of preoperative anxiety, before and after drugs for preoperative medication. After randomization, were clinically and statistically compared 6 groups according to premedicant drugs (diazepam 0.3 mg/kg; flunitrazepam 0.03 mg/kg; saline; prometazine 0.7 mg/kg); before and after preoperative medication were evaluated the anxiety relief with the score scale, haematic levels of DBI and haemodynamics (systolic and diastolic AP and HR). The results show that DBI can objectively measure the anxiety relief, that not are correlate haematic levels of DBI and score scale, that the best benzodiazepines are diazepam (0.3) and flunitrazepam (0.015) and that the prometazine might give anxiety relief for 5-HT antagonist action. Even if there are limits to study (scanty cases, are missing the range and the brain values of DBI and blood test of DBI is slow method) may be useful the use of score scale and haematic levels of DBI in clinical evaluation of preoperative anxiety relief. PMID- 1635635 TI - [The effects of succinylcholine on heart rate and rhythm in infants]. AB - The authors examined the possible variations of cardiac activity in 91 infants aged between a few days and six months in order to study the changes following administration of succinylcholine during general anaesthesia. No variations in rhythm and/or heart rate occurred, not even in those children to whom atropine had not been injected intravenously before succinylcholine. PMID- 1635636 TI - [Loco-regional anesthesia vs general anesthesia in carotid endarterectomy. Response to the surgical stress]. AB - The advantages of performing carotid endarterectomy in the awake patient, perioperative analgesia, circulatory parameters, plasma cortisol and PRL response to surgery have been evaluated. Ten patients were submitted to general anaesthesia and ten patients to superficial and deep cervical block. The Authors conclude that, although the number of patients studied is limited, there are no significant differences between the two groups for intraoperative analgesia, hemodynamic imbalance and plasma cortisol and PRL. This result support the belief that carotid endarterectomy in awake patients can be safely performed on patients with chronic obstructive pulmonary disease. PMID- 1635637 TI - [The propofol-fentanyl-pancuronium combination in aorto-coronary bypass. Experience and personal caseload]. AB - The authors report the use of a total intravenous anaesthesia in CABG. An association of propofol-fentanyl-pancuronium with a bolus at induction, then with continuous perfusion was used. Hemodynamic and oxymetric data obtained from the right heart and radial artery samples show good hemodynamic stability during surgery. It is underlined that, in order to reduce possible hemodynamic changes it is very important to use, during the surgical procedure, the lowest drug concentration. PMID- 1635638 TI - [Endocrine-metabolic response to 2 different techniques in surgery of the abdominal aorta]. AB - Plasma cortisol and PRL were measured in two groups of patients undergoing reconstructive aortic surgery under either general anaesthesia and continuous epidural analgesia with supplemental general anaesthesia. The results confirmed that epidural analgesia with light general anaesthesia is much able than general anaesthesia to suppress the metabolic response associated with aortic surgery procedures. PMID- 1635639 TI - [Plasma levels of mepivacaine in the double block of the sciatic and the femoral nerve]. AB - The large use of double block of sciatic and femoral nerves (bibloc) with high mepivacaine 2% doses (10 mg/kg) has pointed out some cases of toxicity. We found a relationship between shiver and mepivacaine arterious plasma levels higher than 6 micrograms/ml. These symptoms were self-limited and statistically not significant. PMID- 1635640 TI - [A new ventilation method: the laryngeal mask]. AB - A size 3 laryngeal mask was used in 20 patients who underwent elective general surgery. It consists of a silicon tube attached to mask which must be inserted into the hypopharynx and then inflated. No curarisation nor laryngoscopy is needed. Operations were performed in assisted or spontaneous ventilation, with good airway patency and absence of coughing, secretions and sore throat. In 2 cases introduction of the mask failed. Technique, advantages and problems related to its use are described. PMID- 1635641 TI - [The use of Opticath in the correct measurement of the pulmonary capillary wedge pressure]. AB - The Authors assess the utility of the on-line monitoring of SvO2 during 156 measurements of pulmonary capillary wedge pressure (PCWP) done on 52 Intensive Care Unit patients. The measurement was always right when the SvO2 increased more than 90%. The Authors found a good correlation between the SvO2 monitored during the measurement of the PCWP and the saturation of pulmonary capillary blood measured by cooximeter. These data suggest that the complex procedure to confirm the reliability of the measurement recommended by Gardner can be simplified by the observation of the trend of SvO2 on the monitor oximetrix. This allows to obtain saving time for the staff, saving blood for the patients, reduction of risk for the transmission of infective diseases due to the handling of blood and guarantees a further routinary control of reliability on the measure of PCWP. PMID- 1635642 TI - [Circulation effects of noradrenaline in hyperdynamic septic shock]. AB - The authors report on a group of 8 patients in septic shock, treated with NA in association with dopamine and/or dobutamine, according to a personal therapeutic protocol. The use of NA in septic shock with low SVR showed an improvement in hemodynamic condition and a higher survival rate in the treated patients. During the study many clinical, laboratory and microbiologic data were also recorded. PMID- 1635643 TI - [Efficacy and safety of amrinone in the treatment of heart insufficiency in intensive care]. AB - The authors describe the results obtained treating with amrinone for 48 hours 11 patients with acute heart failure. The patients (4 males and 7 females), age range between 50 and 82 years) received an initial bolus of 0.75 mg/kg followed by and infusion which on average was of 5.82 +/- 1.06 (SD) micrograms/kg/min. Besides a subjective and objective clinical improvement they could observe a quick and remarkable improvement of the main hemodynamic parameters (cardiac index, cardiac output, pulmonary capillary wedge pressure, mean pulmonary pressure). The tolerability of the drug was good, except for a decrease in platelet, already described in literature. In conclusion, the Authors consider amrinone a very interesting drug for its positive inotropic and vasodilating activity and because it does not cause an increase of the myocardial oxygen consumption. PMID- 1635644 TI - [Role of oxygen venous saturation monitoring and CAVH in the multiple organ failure syndrome. Description of a clinical case]. AB - A 42 year old man was admitted to the intensive Care Unit with signs and symptoms of septic shock, associated with adult respiratory distress syndrome (ARDS), jaundice and acute renal failure. In order to support different organs failures mechanical ventilation (IPPV, PSV, CPAP), continuous arteriovenous hemofiltration were affected, and continuous intravenous infusion of dopamine and dobutamine was started. After and during application of these therapeutic measures, continuous monitoring of mixed venous blood oxygen saturation (SvO2) was applied by Swan Ganz fiber optic catheter in the pulmonary artery. Monitoring of SvO2 represented a useful means to guide inotropic therapy and to assess the hemodynamic effects of CAVH and mechanical ventilation. The case reported emphasized the role of continuous venous oximetry in multiple organ failure syndrome. PMID- 1635645 TI - [Usefulness of monitoring the mixed venous blood saturation (SvO2) in the diagnosis of heart rupture. A clinical case]. AB - We describe a case report of acute left ventricular free wall rupture during acute myocardial infarction in a sedated and curarised patient. Continuous monitoring of SvO2 was very useful on early diagnosis. PMID- 1635646 TI - [Propofol and fentanyl in Sanfilippo disease. Surgical intervention with adenotonsillectomy]. AB - An intravenous anesthesia with propofol and fentanyl was used for adenotonsillectomy in a child affected by mucopolysaccharidosis. This technique proved to be safe and convenient without peri- and postoperative complications. PMID- 1635647 TI - [New aspects concerning the corpus luteum]. AB - We have summed up current knowledge about the formation and lysis of corpus luteum with the co-ordinate intervention of luteotrophic and luteolytic factors. Then we re-examined the function of the corpus luteum in the physiologic menstrual cycle and in the first period of pregnancy, with special attention to luteal insufficiency as a cause of endocrine miscarriage. PMID- 1635648 TI - [Colpo-cyto-histological correlations in intraepithelial lesions of the uterine cervix]. AB - The aim of this study was to assess the clinical efficiency of colposcopic findings as diagnostic tests for intraepithelial lesion using the analysis of colpo-cyto-histological correlations. The results of 3340 colposcopic tests performed in the Colposcopy Unit of the Second Clinic of Obstetrics and Gynecology between March 1990 and May 1991 were analysed, taking into account 326 (9.7%) cases of Abnormal Transformation Zone (ANTZ). The colpo-histological correlation in ANTZ 1 cases (52 cases of white epithelium, 92 standard mosaic, 42 standard dotted and 61 mixed cases) was 65.2% (52.3%) for HPV; 12.9% for CIN). The colpo-histological correlation in ANTZ 2 cases (30 cases of thickened white epithelium, 5 irregular mosaic, 4 irregular dotted, 2 atypical vessels, 4 thickened gland outlets and 6 mixed cases) was 70.5% (43.3% for HPV; 27.2% for CIN an and Ca). In this retrospective study colposcopy showed a diagnostic accuracy of 64.6% in the cases examined and played a decisive role in the diagnosis of intraepithelial lesions of the uterine cervix. PMID- 1635649 TI - [Clinical aspects of breast cancer in the aged woman]. AB - In Italy breast cancer mortality is constantly increasing in women over 70 years of age. The retrospective analysis of the cases observed at the "Senology Center" of the II Institute of Obstetrics and Gynecology (University "La Sapienza" of Rome) shows when compared to the group of women under age of 40 a higher number of advanced cases. This delayed diagnosis needs a most radical treatment and adjuvant therapies (i.e. chemotherapy) that cannot often be carried out because of general problems. Therefore, elderly women should be sensibilized to undergo periodical and regular sanitary inspection. PMID- 1635650 TI - [Laser CO2: results of treatment of HPV lesions in male the partner]. AB - Hundred-fifty-seven male partners of patients affected by Human Papillomavirus (HPV) lesions, underwent CO2 Laser vaporization between January 1989 and January 1990. The age ranged between 18 and 45 (median 28.2). The vaporization was performed with a Coherent System 451 CO2 Laser equipment, at a power of 16 watt in continuous mode, depth of 2 mm and a free margin of 2 mm. First Laser treatment proved successful in 129 patients (82.1%); 17 out of 28 patients with persistent or relapsed pathology underwent a second CO2 Laser vaporization with a total cure percentage equal to 92.9%. Laser-surgery is the method of choice in the treatment of HPV genital lesions. PMID- 1635651 TI - [Transcervical vs. transabdominal amniocentesis in the bacterial evaluation of the amniotic fluid]. AB - The authors compare the results of bacteriological research on amniotic fluid by transcervical and trans-abdominal amniocentesis. Eighty women at term of their pregnancy, scheduled for cesarean section, underwent a bacteriological vaginal test and a trans-cervical amniocentesis before and a trans-abdominal amniocentesis during cesarean section. The results obtained from both specimens of the amniotic fluid were the same in 90% of the cases. A negative bacteriological result of trans-cervical amniocentesis excluded a positive result of trans-abdominal amniocentesis. Instead, when a positive bacteriological result was obtained in trans-cervical amniocentesis, trans-abdominal amniocentesis gave a positive result in only 60% of the cases. We conclude that trans-cervical amniocentesis, besides being less dangerous, easy to perform and easily repeated, is sufficiently secure and reliable in bacteriological results as compared with trans-abdominal amniocentesis. PMID- 1635652 TI - [Estrogen receptors (ER) and progesterone receptors (PgR) in ovarian cancer]. AB - The paper reviews recent advances regarding interactions between cells and steroid hormones together with the latest data on receptor content in normal and malignant ovarian tissue and their importance in tumoral biology. Three recently published studies confirm that there is an 84% concentration of PgR and 35% of ER in the normal ovary. The incidence of steroid receptors in benign tumours is virtually the same as that found in normal tissue, except for a slight increase in PgR, whereas in malignant ovarian cancer ER and PgR receptors show marked changes. PgR levels fall dramatically from 94% to 42%, while there is a slight rise in ER levels. It has also been demonstrated that low receptor status tumours were more aggressive than those with high receptor positivity in all patients with a follow-up of two or more years. In terms of clinical management, the tumour differences led to the use of synchronised chemohormonal treatment. Preliminary data are encouraging but further research is required to identify the optimal combination. With reference to receptor expression in relation to prognosis it appears clear that receptor-positive tumours have a better prognosis than receptor-negative ones. PMID- 1635653 TI - [Cervix cerclage. A 20-year case load]. AB - Uterine cervical incompetence is the most common cause of habitual abortion in the second trimester of pregnancy and premature delivery; cervical cerclage still represents the only surgical treatment for cervical incompetence. In the last 20 years (1971-1990) we performed 272 Mac Donald cervical cerclages in patients between the 8th and the 34th week of pregnancy. In 16 cases the outcome of pregnancy is unknown; 198 women (73.3%) subsequentely delivered healthy infants later than 37 weeks' gestation or weighing more than 2500 g. PMID- 1635654 TI - [Local anesthesia in cervix biopsy]. AB - The Authors evaluated the perception of pain in a group of 35 patients undergoing cervical biopsy and the efficacy of using 40 mg of lydocaine (xylocaina spray) in 24 patients compared to a control group. Pain perception was evaluated using Scott-Huskissons's visual analogous scale. It was observed that this diagnostic method was painful and that premedication using topical anesthesia was an efficacious method of significantly reducing painful symptoms. PMID- 1635655 TI - [Cytological study of an inflammatory type Pap-test]. AB - The paper reports the results of the study of 900 s of which 630 were of an inflammatory type (70%). The age group most severely affected by phlogosis was that between 35-45 years old with the highest frequency in the group aged between 35-39 years old. Associated pathologies were found in 191 cases (21.2%), with bacterial infections in 101 cases (11.2%), candida in 43 cases (4.8%), T.V. in 17 cases (1.9%), viral infections in 10 cases (1.1%), CIN in 14 cases (1.5%) and malignant tumours in 2 cases (0.22%). PMID- 1635656 TI - [Dermoid cyst associated with planocellular carcinoma]. AB - The case of an ovarian mature cystic teratoma with an associated squamous cell carcinoma is described. The patient, in advanced stage, died a few months after surgery, during the treatment by chemo and radiotherapy. PMID- 1635657 TI - [Crohn disease in pregnancy. Considerations on and discussion of a clinical case]. AB - Crohn's disease with acute abdomen in pregnancy is described. The Authors evaluate Crohn's disease together with the diagnostic, prognostic and therapeutic problems and relationships between this disease and pregnancy. They conclude as underlining the rarity of Crohn's disease beginning in pregnancy and so the importance of symptoms related to this disease in fertile age woman to make diagnosis and therapy before pregnancy. PMID- 1635658 TI - [A case of myomectomy in the course of cesarean section]. PMID- 1635659 TI - Clozapine decreases enkephalin mRNA in rat striatum. AB - Typical antipsychotic drugs (i.e. haloperidol) induce extrapyramidal movement disorders while 'atypical' antipsychotics (i.e. clozapine) do not. In situ hybridization histochemistry followed by film autoradiography showed that clozapine treatment (20 mg/kg i.p. daily for 28 days) decreased the level of labelling for preproenkephalin mRNA in the striatum of the rat while haloperidol treatment (1 mg/kg i.p. daily for 28 days) resulted in no change compared with controls. The results suggest that these typical and atypical antipsychotic drugs exert differential effects on the enkephalin-containing striatal projection to the globus pallidus, a pathway critical for the expression of extrapyramidal movement disorders. PMID- 1635660 TI - Differential membrane properties and dopamine effects in the shell and core of the rat nucleus accumbens studied in vitro. AB - Electrophysiological differences between the shell and core of the rat nucleus accumbens were investigated by intracellular recordings from an in vitro slice preparation. The average input resistance of neurons recorded in the shell was larger than in the core. Neurons in the core were characterized by a more negative resting membrane potential than neurons in the shell. Furthermore, bath applied dopamine attenuated synaptic responses recorded in the shell, but not in the core. Thus, the two main subregions of the nucleus accumbens differ both in basal membrane properties and in dopaminergic modulation of synaptic transmission. PMID- 1635661 TI - Serotonin may have neurotoxic properties. AB - Serotonin (5HT), a major platelet secretory product, has been shown to suppress CNS function in vivo. As part of an ongoing project to study interactions between neuron and platelet, we used organotypic explant cultures of rat spinal cord to study if 5HT had a morphologically demonstrable neurotoxic effect. The results suggest that serotonin may be neurotoxic, and that this effect may be prevented by ketanserin, a specific 5HT2 antagonist. Related experiments, using acetylcholinesterase (AChE) enzyme activity as a biochemical parameter, indicate that 5HT hastens the decline of enzyme activity. The concentrations of 5HT at which neurotoxicity was demonstrated were comparable to the calculated 5HT concentration potentially present in the vicinity of an acute cerebral thrombus. These findings could provide new insight into the mechanism of ischemic neuronal injury. PMID- 1635662 TI - Effects of estradiol treatment on responses of rat preoptic warm sensitive neurons to progesterone in vitro. AB - Single unit activity was recorded extracellularly in preoptic slice preparations from ovariectomized female rats. The rats were pretreated daily with (1) estradiol benzoate (20 micrograms/0.1 ml sesame oil) for 3 consecutive days just prior to the experiment (OVX+E72h), (2) sesame oil (OVX+Oil), or (3) untreated (OVX). In the preparations from OVX rats, 12 (50%) of 24 warm-sensitive neurons were inhibited and 2 (8%) were excited by the application of progesterone (P) in perfusion medium (30 ng/ml). In OVX+Oil preparations, 4 (40%) of 10 warm sensitive neurons were inhibited and none was excited by P. In OVX+E72h preparations, however, only 4 (10%) were inhibited by P and 16 (38%) of 42 warm sensitive neurons were excited. When Ru38486, a P-receptor antagonist, was applied together with P, no excitation was observed in warm-sensitive neurons in OVX+E72h preparations. These findings suggest that the P-induced excitation of preoptic warm sensitive neurons is mediated through the estrogen-induced P receptors. PMID- 1635663 TI - Quantitative differences in the deposition of beta A4 protein in the sulci and gyri of frontal and temporal isocortex in Alzheimer's disease. AB - The distribution of beta-amyloid protein (beta A4) in the frontal and temporal isocortex of 14 Alzheimer's disease brains was examined using a combination of immunohistochemistry and computer image analysis. The area of cortex covered by beta A4 deposits was determined and expressed as a percentage of the total cortical grey matter area in each field of interest. Significantly more beta A4 was found in the grey matter of the sulci as compared to that of the gyral crests in both the frontal and the temporal lobes (P less than 0.05). Furthermore, in each case, greater quantities of beta A4 were observed in the frontal rather than the temporal lobes. This apparent differential vulnerability is likely to reflect underlying anatomical connections or perhaps differences in cell packing density and appears to strengthen the case for an anatomical basis for the spread of the disease pathology. PMID- 1635664 TI - Absence of c-fos induction in neonatal rat brain after seizures. AB - Induction of the proto-oncogene c-fos is often considered to be a marker of increased neuronal activity. We have used in situ hybridization to study the pattern of c-fos expression in limbic structures following kainic acid-induced seizures during the postnatal period in the rat. Prior to postnatal day 13 (P13), seizure activity did not result in c-fos induction in any limbic structure. Between P13 and P25, a gradual increase in c-fos expression was observed in hippocampus and cortical structures. These results were corroborated by nuclear run-off transcription assay. Thus, alterations in c-fos transcription that may facilitate stimulus-transcription coupling occur during postnatal development. The possible relationship between the postnatal maturation of c-fos expression and the increase in susceptibility of specific neuronal populations to seizure induced cell damage is discussed. PMID- 1635665 TI - Inhibitory effect of neuropeptide Y (NPY) on the in vitro activity of dopamine beta-hydroxylase. AB - Neuropeptide Y (NPY) is found to be costored with norepinephrine (NE) in vesicles of the nerve terminals. An endogenous inhibitor of dopamine-beta-hydroxylase (DBH), the synthetic enzyme of NE, has been mentioned. In an attempt to clarify the effect of NPY on DBH activities, an in vitro assay is carried out using chromatographic analysis of NE formation from dopamine. NPY (20-80 pmol/ml) produced a dose-dependent depression of NE formation catalysed by the purified bovine adrenal DBH. Lineweaver-Burke plots (Km = 1.1 mM, Vmax = 10 pmol/min/mg protein) showed a non-competitive inhibition in NPY (30 pmol/ml, IC50)-treated samples. Moreover, failure of denatured NPY even at maximum concentration to influence the DBH activities suggested the essential of natural form of NPY. Participation of sulfhydryl compound seems also negligible, because N ethylmaleimide did not overcome the effect of NPY. These results indicate that NPY has the ability to inhibit the catalytic action of DBH. PMID- 1635666 TI - Antidromic and synaptic activation of Deiters' neurons induced by stimulation of red nucleus in the cat. AB - Antidromic and orthodromic action potentials of neurons located in the lateral vestibular nucleus of Deiters' evoked by stimulation of red nucleus were studied in anaesthetized cats. Vestibulospinal neurons were identified by stimulation of the lateral vestibulospinal tract. The 'second-order' vestibular neurons were revealed by mean of stimulation of the ipsilateral VIIIth nerve. Stimulation of the red nucleus is shown to lead mainly to antidromic, as well as mono-, oligo- and polysynaptic activation of Deiters' neurons. Not any inhibitory reaction was observed in vestibular neurons in response to stimulation of the red nucleus. Ascending axon collaterals of the vestibulospinal neurons to this brainstem structure were revealed. The peculiarities and functional significance of the effects mentioned are discussed. PMID- 1635667 TI - The role of local contrast in the visual deficits of humans with naturally occurring amblyopia. AB - We measured the positional acuity of amblyopic observers and their sensitivity to the local contrast information which provides the cue for the position judgement. Our results suggest that there exist fundamental differences in the neural losses in humans with strabismic and anisometropic amblyopia. The losses in positional acuity of anisometropic amblyopes may be accounted for on the basis of the reduced contrast sensitivity and increased neural pooling of the underlying visual filters; whereas strabismic amblyopes, like the normal periphery, show an extra loss, which may be accounted for on the basis of scrambling, or jitter in the topographic mapping of information from retina to cortex. Since neurons in the striate cortex of monkeys show precise positional coding, it would be of particular interest to examine the positional acuity and local contrast sensitivity in cortical neurons of monkeys with experimental amblyopia using the same stimuli to measure both. PMID- 1635668 TI - Expression of GAD mRNA in GABA interneurons of the rat medial frontal cortex. AB - The distribution of glutamic acid decarboxylase (GAD) mRNA containing cells was studied in the rat medial frontal cortex (MFC). The neurons labelled by the 35S labelled cDNA probe were distributed uniformly throughout all the layers and represented 16% of the total neuronal population. It was possible to distinguish two cell populations expressing high and low levels of GAD mRNA corresponding to 63% and 27% of labelled cells, respectively. Concerning the laminar distribution of these two populations of GAD mRNA containing neurons, no marked difference was observed between the various areas of the MFC. PMID- 1635669 TI - Relationships between electrically induced slow negative potentials and changes in extracellular potassium concentrations in cerebral cortex of the cat. AB - Experiments were carried out on cats under deep nembutal anaesthesia. Local cortical stimulation evoked both a slow negative potential (SNP) and an increase in extracellular potassium ([K+]o) which were maximal in the upper cortical layers. The decline in the K(+)-potential in deeper layers was slower than in the upper ones so that with time [K+]o became equal in upper and deeper layers. No SNP was recorded at that time, perhaps explaining why K(+)-potential decay is of longer duration than the SNP. Transcallosal stimulation also evoked an SNP but gave a lesser difference in delta [K+]o in upper and deeper layers. The lower amplitude of the SNP evoked by transcallosal stimulation may be due to these circumstances. These data could clarify the mechanism of correlation disturbance between SNPs and K(+)-potentials in the cerebral cortex. PMID- 1635670 TI - Alzheimer's amyloid precursor protein accumulates within axonal swellings in human brain lesions. AB - By using a monoclonal antibody and polyclonal antibodies to human beta amyloid precursor protein (APP), we immunohistochemically examined axonal swellings (spheroids). The immunoreactivity of APP was observed in numerous spheroids, which were found around the areas of old cerebral infarctions, in the globus pallidus with Hallervorden-Spatz disease as well as in or around brain abscesses. The axonal swellings were not immunolabeled with beta protein. These results implied that APP accumulated in spheroids regardless of beta protein depositions. PMID- 1635671 TI - Gpp(NH)p stimulates [3H]raclopride binding to homogenates from human putamen and accumbens. AB - The effects of the stable GTP analogue Gpp(NH)p (5'-guanylyl imido diphosphate) were examined on in vitro [3H]raclopride binding to dopamine D2 receptors in preparations from post mortem human brains. The estimated number of receptors in the brain was 29% and 38% higher in putamen and accumbens, respectively, when determined in the presence of Gpp(NH)p as compared to its absence. The interaction of agonists was biphasic confirming the two affinity state model of the receptor--G-protein complex. The addition of Gpp(NH)p to the assay abolished the two site competition of apomorphine with [3H]raclopride binding in both regions studied. The non-specific binding at high concentrations of apomorphine was not significantly affected by the addition of Gpp(NH)p, indicating that only the specific binding of [3H]raclopride to the dopamine D2 receptor is increased. PMID- 1635672 TI - Deficient corpus callosum in hybrids between ddN and three other abnormal mouse strains. AB - The mouse strain ddN from Japan was crossed with three other inbred strains prone to absence of the corpus callosum (BALB/cWah1, I/LnJ and 129/ReJ), and at least one brain with abnormally small corpus callosum was observed in offspring from each F1 hybrid cross. Data for several polymorphic protein markers revealed that the four strains are not closely related genetically. Nevertheless, they share common genetic causes of an absent corpus callosum, which helps to understand why anatomical studies of ddN and BALB/c have yielded similar results. The hippocampal commissure is abnormally small in I/LnJ mice and the anterior commissure is often malformed in BALB/c mice, but both commissures in hybrids were normal, which suggests a different genetic basis for these defects and the absent corpus callosum. PMID- 1635673 TI - PT requirements for physician office laboratories. AB - The Clinical Laboratory Improvement Amendments of 1988 (CLIA-88) regulations will require physician office laboratories (POLs) to participate in proficiency testing (PT) for all nonwaivered tests performed in private offices. PT will enhance the quality of the testing performed in a POL. PMID- 1635674 TI - Personnel recordkeeping requirements for CLIA-88. AB - Documented personnel files will be a requirement of the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88) regulations. This documentation will help reduce laboratory errors and liability by clearly and completely defining the employee's duties and responsibilities. PMID- 1635675 TI - Evaluation of prothrombin time and partial thromboplastin time. AB - Prothrombin time (PT) and partial thromboplastin time (PTT) tests are commonly ordered for hospitalized patients. A significant reduction in laboratory workload and expense can be achieved if these tests are ordered appropriately. The likelihood that the patient will benefit from these tests is small. PMID- 1635676 TI - Why bother the New Jersey State Department of Health? AB - The reporting of communicable diseases is a legal and professional responsibility. Individual case reports can be an important piece in a medical puzzle, allowing public health officials to describe new diseases and modes of transmission so preventive measures can be developed and implemented. PMID- 1635677 TI - Phagocytosis of Candida parapsilosis by polymorphonuclear leukocytes. AB - The authors present a brief case report on an unusual entity. This rare phenomenon observed in a peripheral smear is worth noting. Neutrophils and rare eosinophils show intracellular fungal cells; the size, shape, and budding are consistent with Candida parapsilosis. PMID- 1635678 TI - Medium chain acyl-coenzyme A dehydrogenase deficiency and SIDS. AB - Medium chain acyl-coenzyme A dehydrogenase deficiency (MCADD) is a potentially fatal genetic defect in fatty acid metabolism and may account for a proportion of all deaths initially attributed to sudden infant death syndrome (SIDS). Effective therapy and prevention are available. PMID- 1635679 TI - The diagnosis and management of depression: an overview. AB - The authors present an overview of the diagnosis, treatment, and management of depressed patients. They discuss current psychotherapeutic techniques, the psychopharmacologic management of depression, and guidelines for referral of depressed patients to mental health professionals. PMID- 1635681 TI - How do we look? PMID- 1635680 TI - Federal PRO program undergoing fundamental transformation. AB - The PRO of New Jersey, Inc. is committed to the ideal of a localized peer review process--one that is based on the belief that New Jersey physicians are best suited to assess the work of their peers. The concept of a local peer review remains absolutely essential. PMID- 1635682 TI - Reform in workplace key to claim. PMID- 1635683 TI - Banking on breast milk. PMID- 1635684 TI - Competition in health: fear is the key. PMID- 1635685 TI - Teaching cultural safety. PMID- 1635686 TI - The making of a TV commercial. PMID- 1635687 TI - Four honoured for rescue role. PMID- 1635688 TI - Comments on the "exception...". PMID- 1635689 TI - Auxiliary personnel can increase productivity. PMID- 1635690 TI - Head nurse and CNS: teaming up. PMID- 1635691 TI - International exchange programs and recruitment. PMID- 1635692 TI - Ambulatory surgery: integrating the preadmission program. PMID- 1635693 TI - A computerized CIS enhances bedside intensive care. PMID- 1635694 TI - Protecting children: a public duty to report. PMID- 1635695 TI - On writing a column on ethics. PMID- 1635696 TI - LTC: there's no place like home. PMID- 1635697 TI - What nursing leaders are saying about technology. PMID- 1635698 TI - Building careers: AONE's new center. American Organization of Nurse Executives. PMID- 1635699 TI - Informatics: managing clinical operations data. PMID- 1635700 TI - Charting: the impact of bedside computers. PMID- 1635701 TI - Automated patient care systems: the ethical impact. PMID- 1635702 TI - Nursing practice: promoting computer literacy. PMID- 1635703 TI - Males in nursing. PMID- 1635704 TI - A new perspective on scheduling: freedom and cost control. PMID- 1635705 TI - Nurse managers and clinical nursing research. PMID- 1635706 TI - MBFT--management by follow-through. PMID- 1635707 TI - Signs of things to come. PMID- 1635708 TI - Evaluation instruments to measure professional nursing practice. PMID- 1635709 TI - Patient advocacy: the role of nursing leadership. PMID- 1635710 TI - 1992 software guide. PMID- 1635711 TI - Manufacturers disappoint. PMID- 1635712 TI - On guard. PMID- 1635713 TI - 100 percent dentists. PMID- 1635714 TI - Where past and future intersect. PMID- 1635715 TI - Forces of change. PMID- 1635716 TI - Meeting the curriculum challenge. PMID- 1635717 TI - New horizons in periodontics. The challenge for diagnosis. AB - Contemporary periodontics offers successful treatment for most cases of periodontitis. The data analyzed in this paper suggest, however, that a large percentage of the population in our region suffers from established, overt periodontitis and does not receive periodontal therapy. Guidelines and the sensitivity and specificity of detection, using present-day clinical procedures of periodontal pocket probing and radiograph analysis, are described for the detection of patients with established, overt periodontitis. PMID- 1635718 TI - Buffalo School of Dental Medicine. The way it was. PMID- 1635719 TI - Adhesion of direct restorative materials. AB - The development of adhesive restorative systems has been a major focus in dentistry. Materials that can attach to tooth structure make it possible to take a far more conservative approach to restorative dentistry. PMID- 1635721 TI - AIDS patients need dental care. PMID- 1635720 TI - HHC to study oral aspects of AIDS. PMID- 1635722 TI - Celebrating the U.B. centennial. PMID- 1635723 TI - Second opinion. PMID- 1635724 TI - The role of selection bias in comparing cesarean birth rates between physician and midwifery management. AB - OBJECTIVE: The midwifery service at our hospital has been observed to have a 2% cesarean birth rate consistently over a 10-year period. There are substantial differences in labor management style between the midwives and physicians. We sought to test the hypothesis that the low cesarean birth rate on the midwifery service was the result of patient selection bias. METHODS: A randomized blinded clinical trial was conducted in which 492 low-risk patients were assigned to either physician or midwifery management. The provider responsible for labor management was unable to determine group assignment. Patients in the midwifery group were managed by previously established protocols, and outcome was attributed to the midwives even if the patients subsequently required transfer to physician management. Route of delivery was the primary outcome measurement. Continuous variables were analyzed using Student t test and discrete variables using chi 2. RESULTS: There were no demographic differences between the groups, and the admission pelvic examinations were the same. The patients assigned to the midwifery group had a 2.1% cesarean birth rate, whereas those assigned to physician management had a 0.4% rate. The higher rate of operative vaginal deliveries in the physician group was statistically significant. There were no differences in neonatal outcomes. The physician-managed group had significantly more episiotomies and third- and fourth-degree extensions. CONCLUSIONS: The 2% cesarean birth rate observed on the midwifery service appeared to be the result of patient selection bias. A low cesarean birth rate can be achieved by either physician or midwifery management in a selected low-risk population. PMID- 1635725 TI - Unfavorable outcome in penultimate pregnancy and premature rupture of membranes in successive pregnancy. AB - OBJECTIVES: Previous adverse obstetric events are known to influence the outcome of the succeeding pregnancy. We tested the hypothesis that preterm premature rupture of membranes (PROM), full-term PROM, and preterm delivery without PROM relate independently to the outcome of the immediately preceding pregnancy. METHODS: In a case-control study, 345 women 15-45 years old with preterm PROM, full-term PROM, or preterm delivery without PROM were singly matched by age, race, and parity to women having full-term delivery. Information about the penultimate pregnancy, household smoking, and sociodemographic variables were obtained during face-to-face interviews. Obstetric history, infections during pregnancy, and pregnancy complications abstracted from medical records were cross checked with patient interview data. Penultimate pregnancy outcomes included full term delivery, premature delivery, fetal loss or miscarriage, and planned abortion. RESULTS: Women having preterm PROM or preterm delivery without PROM in the index pregnancy were, respectively, 6.34 and 21.28 times more likely than controls to have had preterm delivery in the preceding pregnancy. A preceding fetal loss or miscarriage also increased 4.39-fold the risk for preterm PROM. Exposure to cigarette smoke, urinary tract infections, and vaginal bleeding during the index pregnancy independently increased the risk for preterm PROM. Women with full-term PROM did not differ significantly from controls in the outcomes of the penultimate pregnancy. CONCLUSION: Preterm delivery in the preceding pregnancy is associated with an increased risk for preterm delivery with or without PROM. PMID- 1635726 TI - Bacterial vaginosis in early pregnancy and pregnancy outcome. AB - OBJECTIVE: We assessed the association between bacterial vaginosis in early pregnancy and adverse pregnancy outcome. METHODS: Vaginal swabs for bacterial culture, Gram stain, and Papanicolaou stain were taken at the first prenatal visit between 8-17 weeks' gestation in 790 healthy nulliparous women. RESULTS: Culture-proven bacterial vaginosis was detected in 169 of 790 women (21.4%), 167 (98.8%) of whom could also be identified by Gram stain. Papanicolaou smears were available from 299 women, among whom 101 had bacterial vaginosis on culture; of these 101, 78 (77.2%) could be detected by Papanicolaou stain. Of the 751 women whose clinical follow-up was completed, 42 had been treated for preterm uterine contractions (preterm labor), but only 17 delivered between 20-36 weeks' gestation (preterm birth). Premature rupture of membranes (PROM) occurred more than 6 hours before delivery in 80 cases (nine preterm and 71 term). Bacterial vaginosis in early pregnancy predicted preterm labor, preterm birth, or preterm PROM with a sensitivity of 41-67%, specificity of 79%, and negative predictive value of 96-99%, but the positive predictive value was low at 4-11%. However, bacterial vaginosis was associated with a 2.6-fold risk (95% confidence interval [CI] 1.3-4.9) for preterm labor, a 6.9-fold risk (95% CI 2.5-18.8) for preterm birth, and a 7.3-fold risk (95% CI 1.8-29.4) for preterm PROM. CONCLUSIONS: Bacterial vaginosis in early pregnancy can be detected reliably by Gram stain and, in most cases, by Papanicolaou smear. Although bacterial vaginosis is associated with preterm labor, preterm birth, and preterm PROM, the clinical usefulness of its assessment is limited because of the high rate of false positive findings. PMID- 1635727 TI - Myasthenia gravis in pregnancy. AB - OBJECTIVE: Our purpose was to review our experience with nine cases of myasthenia gravis complicating pregnancy. METHODS: We reviewed the records of all patients discharged from the Vancouver Salvation Army Grace Hospital from January 1979 to January 1989 with an admission diagnosis of myasthenia gravis in pregnancy. RESULTS: Nine patients delivered 11 infants. Four suffered antepartum exacerbations. The most severe of these, respiratory failure, occurred in a thymectomized patient. Labor was rapid and uncomplicated except for a single case of cephalopelvic disproportion delivered abdominally. We noted no puerperal exacerbations. Our solitary case of neonatal myasthenia gravis was managed in the special care nursery with intramuscular neostigmine given over a 16-day period. CONCLUSION: There are no predictive factors that identify the mother at risk for peripartum exacerbation of myasthenia gravis or the infant at risk for neonatal myasthenia gravis. Optimal care for the parturient is achieved through a team approach involving the obstetrician, neurologist, and pediatrician. PMID- 1635728 TI - Pharmacokinetics of salbutamol in the pregnant woman after subcutaneous administration with a portable pump. AB - OBJECTIVE: We sought to determine whether subcutaneous administration of salbutamol resulted in plasma levels comparable to those achieved after intravenous or oral administration. METHODS: Twenty-nine women with preterm labor received subcutaneous infusion of salbutamol through a portable pump. We used three different rates of continuous infusion: a low rate of 3.33 micrograms/minute (20 subjects), an intermediate rate of 6.66 micrograms/minute (four subjects), and a high rate of 9.99 micrograms/minute (five subjects). Plasma salbutamol concentrations were assayed by high-performance liquid chromatography after 48 hours of continuous infusion in the subcutaneous tissue and after bolus injections (184 micrograms in the low-rate group and 368 micrograms in the intermediate- and high-rate groups). RESULTS: Plasma salbutamol concentrations after 48 hours of subcutaneous infusion increased almost linearly with the rate of infusion: 6.29 +/- 1.58, 15.5 +/- 1.0, and 21.7 +/- 4.26 ng/mL in the low-, intermediate-, and high-rate groups, respectively (P less than .001 between the three groups). After bolus injection, maximum plasma concentrations were significantly different between the three groups (P less than .001) and from their respective baseline values (P less than .001): 8.33 +/- 1.9, 18.85 +/- 2.0, and 25.86 +/- 4.8 ng/mL in the low-, intermediate-, and high-rate groups, respectively. CONCLUSION: Subcutaneous tocolysis can provide plasma salbutamol levels similar to the levels obtained orally or intravenously. PMID- 1635729 TI - Sound levels in the human uterus. AB - OBJECTIVE: We sought to determine the degree to which noises and voices are attenuated or enhanced as they pass into the uterus. METHODS: In eight parturients, a hydrophone in the uterus was used to measure sound pressure levels for externally generated one-third-octave band noises, male and female voices, and the subject's voice. RESULTS: Low-frequency sounds (0.125 kHz) generated outside the mother were enhanced by an average of 3.7 dB. There was a gradual increase in attenuation for increasing frequencies, with a maximum attenuation of 10.0 dB at 4.0 kHz. Sound attenuation was slightly less if the insonation was from in front of the woman rather than behind. Intrauterine sound levels of the mother's voice were enhanced by an average of 5.2 dB, whereas external male and female voices were attenuated by 2.1 and 3.2 dB, respectively. The effect of frequency on attenuation, the differences between front and back insonation, and the differences between speakers in attenuation were all statistically significant. CONCLUSIONS: The intrauterine environment is rich with externally generated sounds. This may imply fetal risk from maternal noise exposure and may aid in understanding fetal imprinting from prenatal exposure to voices. PMID- 1635730 TI - High rates of atypical cervical cytology: occurrence and clinical significance. AB - The current literature suggests that atypical (benign atypia or class II) Papanicolaou smears occur at a frequency of 1.6-5.4% and are associated with a substantial rate of underlying cervical dysplasia. However, we noted that our rate of atypia exceeded these figures, particularly in our clinic population. To quantify this observation, 1107 consecutive Papanicolaou smears from the clinic population were audited prospectively and compared with 262 consecutive Papanicolaou smears performed contemporaneously in private patients served by the same laboratory. The rate of histologic dysplasia underlying this diagnosis was assessed by analyzing the results of 101 consecutive colposcopic examinations performed subsequently on clinic patients evaluated for persistently atypical cytology (atypical index smear followed by repeat cytology scheduled 2-4 months later). The prevalence of atypia in the clinic population was 321 of 1107 (29%; 95% confidence interval [CI] 26-32%), a rate 2.3 times that of the private patients (33 of 262, 13%) (P less than .001). Eighteen of 101 clinic patients with persistent atypia had dysplasia (18%; 95% CI 11-25%), and 25 of 101 (25%; 95% CI 17-33%) had human papillomavirus infection, both documented by the histology of directed cervical biopsies. Cervical intraepithelial neoplasia grade II or higher was present in three of these 18 women (17%; 95% CI 6-39%). We conclude that some populations have atypical cervical cytology at a frequency much greater than that reported previously. Furthermore, the pathology underlying this diagnosis is considerable and warrants evaluation. The optimal management of atypical cervical cytology in such populations is problematic. PMID- 1635731 TI - The significance of peritoneal cytology in stage IB cervical cancer. AB - OBJECTIVE: The purpose of this study was to determine the incidence of positive peritoneal cytology and to evaluate its usefulness in the management of patients with early-stage cervical cancer. METHODS: Peritoneal cytology was studied in 273 women undergoing primary surgical exploration for International Federation of Gynecology and Obstetrics stage IB cancer of the cervix. Charts were reviewed retrospectively for clinicopathologic data concerning tumor size, cell type, lymph node status, and outcome. RESULTS: Cytology was positive in four women, three of whom had enlarged pelvic or para-aortic lymph nodes or intraperitoneal disease. There was no association between tumor histology or tumor size and peritoneal cytology. CONCLUSION: The incidence of positive peritoneal cytology in early-stage cervical cancer is low, and the prognostic significance of positive cytology is overshadowed by other risk factors more obvious at surgery. The routine collection of cytologic specimens at laparotomy should be abandoned in this setting. PMID- 1635732 TI - Invasive cervical cancer complicating intrauterine pregnancy: treatment with radical hysterectomy. AB - OBJECTIVE: Radical hysterectomy and bilateral pelvic lymph node dissection have become the mainstay of treatment for early-stage cervical cancer because of both a high success rate and acceptable morbidity. However, those cervical lesions that occur concomitant with an intrauterine pregnancy have historically been treated with irradiation. We report the morbidity and results of radical hysterectomy and bilateral pelvic lymph node dissection for the treatment of early-stage cervical cancer complicating intrauterine pregnancy. METHODS: Between 1955-1991, 13 patients were treated with radical hysterectomy and bilateral pelvic lymph node dissection with the fetus in situ, and eight others with cesarean delivery followed by radical hysterectomy and bilateral pelvic lymph node dissection. Charts were reviewed retrospectively. RESULTS: Mean operative time was 281 minutes. The mean blood loss was 777 mL with radical hysterectomy and bilateral pelvic lymph node dissection alone, and 1750 mL with cesarean delivery, radical hysterectomy, and bilateral pelvic lymph node dissection (P less than .01). Intraoperative morbidity included a single accidental cystotomy that was complicated in the postoperative period by a vesicovaginal fistula. Fever was the most common postoperative cause of morbidity (29%), while two patients (10%) had wound seromas and a single patient (5%) each had a pulmonary embolism, cystitis, and transfusion-related hepatitis. No perioperative deaths occurred. After documentation of maturity, seven healthy infants were delivered with no major morbidity. Twenty patients (95%) are alive and free of disease with a mean follow-up of 40 months. CONCLUSION: Radical surgery offers immediate treatment for early-stage cervical cancer during intrauterine pregnancy, with low associated morbidity, acceptable survival, and preservation of ovarian function. PMID- 1635733 TI - The value of exploratory laparotomy in patients with endometrial carcinoma according to the new International Federation of Gynecology and Obstetrics staging. AB - OBJECTIVE: We conducted a retrospective review of 169 consecutive patients diagnosed with endometrial carcinoma to evaluate the advantage of exploratory laparotomy according to the new International Federation of Gynecology and Obstetrics (FIGO) classification as compared with clinical staging. METHODS: All 169 patients were admitted to the Department of Gynecologic Oncology from August 1980 through June 1988 and underwent exploratory laparotomy, which included total abdominal hysterectomy, bilateral salpingo-oophorectomy, and peritoneal washings. We performed complete lymph node dissection of the pelvic and the para-aortic areas on 87 patients with clinical stages I and II. Eighteen more patients were upgraded to stage III or IV during exploratory laparotomy with lymph node biopsy. Forty-nine patients did not have lymph node dissection because of age and medical contraindications. In 15 patients with clinical stage III or IV, lymph node dissection was performed as part of debulking surgery. Clinical staging showed 135 patients (80%) with stage I, 19 (11%) with stage II, three (2%) with stage III, and 12 (7%) with stage IV carcinoma. RESULTS: Surgical restaging according to the new FIGO classification resulted in 117 patients (69%) with stage I, seven (4%) with stage II, 23 (14%) with stage III, and 22 (13%) with stage IV carcinoma. Thirty patients (19%) of 154 with clinical stage I or II had extrauterine spread. Thirty-three of 169 patients (19.5%) had their clinical staging upgraded and six (3.5%) were downgraded. The 5-year actuarial survival rates for clinical stages I, II, and IV were 83, 64, and 8%, respectively. The actuarial survival rates for surgical stages I, II, III, and IV were 89, 100, 58, and 24%, respectively. Cases surgically staged as I with high-risk variables (eg, poor differentiation, unfavorable histologic types, and deep myometrial invasion) or stage II received 5000 cGy to the whole pelvis using a box technique. Patients with surgical stage III or IV received adjuvant intravenous chemotherapy (eg, doxorubicin, hydrochloride, Cytoxan, and cisplatin) consecutively for ten to 12 courses. Megestrol acetate was added for 2 years. CONCLUSIONS: Surgical staging after exploratory laparotomy defined the true extent of disease and identified 20% of the cases that may escape effective treatment. PMID- 1635734 TI - Uterine leiomyomas: cytogenetic and histologic profile. AB - OBJECTIVE: The main purpose of this study was to determine whether there is any correlation between the cytogenetic abnormalities and histology in uterine leiomyomas. METHODS: A total of 93 benign uterine leiomyomas were included in the study. The majority (88 of 93) were classified as typical benign leiomyomas, four as cellular, and one as atypical symplastic. RESULTS: A normal chromosome complement (46,XX) was observed in approximately 50% of the cases (41 of 93). Seventeen leiomyomas did not grow sufficiently in culture to yield cells for chromosome analyses. Of the 35 cases with clonal abnormalities, 28 could be divided into four major subgroups, each representing one of the most common abnormalities observed, such as those of chromosomes 1, 7, and 13, and t(12;14). CONCLUSIONS: Our findings indicate that approximately 50% of leiomyomas show clonal abnormalities, which can be subdivided into four different major categories; four of five (80%) of the atypical leiomyomas showed clonal chromosome abnormalities, which in one case were complex. The results indicate that different specific chromosome abnormalities may characterize the same tumor type. PMID- 1635736 TI - The possible role of endothelial cells in hypertensive disorders during pregnancy. AB - OBJECTIVE: To clarify the role of endothelial cells in pregnancy-related hypertensive disorders, we studied the cytotoxic effect of sera from normal pregnant women and from gravidas with various hypertensive complications of pregnancy. METHODS: We obtained serum samples from 84 Japanese women: 17 with preeclampsia, ten with gestational hypertension, six with chronic hypertension, five with chronic hypertension with superimposed preeclampsia, 21 normal gravidas, and 25 healthy nonpregnant women. Endothelial cell injury was measured by the release of radiolabeled chromium from the cells into the culture medium. RESULTS: The mean (+/- standard error of the mean) values of chromium 51 release in preeclampsia, gestational hypertension, chronic hypertension, chronic hypertension with superimposed preeclampsia, normal pregnancy, and healthy nonpregnant women were: 21.9 +/- 2.1, 10.0 +/- 2.0, 9.2 +/- 2.3, 12.9 +/- 0.8, 8.4 +/- 1.4, and 7.3 +/- 1.6%, respectively. Normal pregnant and nonpregnant subjects did not differ with respect to endothelial cell injury. Sera from women with preeclampsia demonstrated significantly greater endothelial cell injury than did sera from normal gravidas. Subjects with the three other categories of hypertensive disorders did not differ significantly from normal gravidas. CONCLUSION: Preeclampsia is characterized by the presence of a serum factor cytotoxic to endothelial cells. Therefore, the mechanism responsible for the increase in blood pressure differs between women with preeclampsia and those with other hypertensive disorders in pregnancy. PMID- 1635735 TI - Changes in serum electrolytes after transcervical resection of endometrium and submucous fibroids with use of glycine 1.5% for uterine irrigation. AB - OBJECTIVE: We evaluated the postoperative changes in serum electrolytes in relation to the amount of irrigating fluid absorption and the occurrence of nausea and vomiting after transcervical resection of endometrium and submucous fibroids. METHODS: From May 1989 to October 1991, 101 consecutive patients were operated on for menometrorrhagia with transcervical resection of endometrium and submucous fibroids using glycine 1.5% for uterine irrigation. The deficit of glycine was assessed during and at the end of the operation. During the postoperative course, attention was paid to the occurrence of cerebral confusion, nausea (defined by at least one incident of vomiting), and dyspnea. The serum levels of sodium, potassium, and chloride were assessed before the operation, at the end of the procedure, and after 4, 8, and 12 hours. RESULTS: No marked water intoxication or signs of volume overload were seen, but 33% of the patients had nausea and vomiting in the postoperative period. These patients showed a more pronounced postoperative decrease in serum sodium (P = .0001) and a larger glycine deficit (P = .004) than did patients without nausea. The postoperative decrease in serum sodium correlated significantly to the glycine deficit (R2 = 0.83, P less than .001). CONCLUSION: Postoperative hyponatremia after transcervical resection of the endometrium correlated with the deficit of irrigant fluid but not with the operation time or the total amount of irrigant fluid used. We recommend that serum sodium be controlled and corrected if necessary postoperatively in patients with nausea and vomiting. PMID- 1635737 TI - A randomized clinical trial comparing the Cytobrush and cotton swab for Papanicolaou smears. AB - OBJECTIVE: We sought to determine whether use of the Cytobrush/spatula or the cotton swab/spatula is better in obtaining satisfactory Papanicolaou smears as defined by the Bethesda System. METHODS: This 1-year randomized trial was performed at the Los Angeles County + University of Southern California Women's Hospital colposcopy clinic. Participants were all nonpregnant patients referred to the colposcopy clinic for abnormal Papanicolaou smears. The main outcome measurement was the effectiveness in obtaining satisfactory Papanicolaou smears as defined by the Bethesda System. Data were analyzed using the Pearson chi 2 test. RESULTS: The sampling methods had similar abilities to obtain a satisfactory smear (Cytobrush/spatula 63%, cotton swab/spatula 57%; P = .23). Less-than-optimal smears accounted for 28% of the Cytobrush group and 38% of the cotton-swab group. The Cytobrush was superior in its ability to obtain endocervical cells (Cytobrush 80%, cotton swab 60%; P less than .01). Both sampling methods had similar rates of correlation with histologic diagnosis. No complications were associated with either technique. CONCLUSIONS: The Cytobrush/spatula is superior to the cotton swab/spatula in obtaining endocervical cells. There appears to be no difference in each method's ability to obtain satisfactory smears. Application of the Bethesda System results in a significant number of less-than-optimal smears using either technique. PMID- 1635738 TI - Ilioinguinal nerve entrapment during needle suspension for stress incontinence. AB - The anatomy of the ilioinguinal nerve makes it vulnerable to entrapment near its exit from the superficial inguinal ring, where it lies almost directly superior to the pubic tubercle. During a 27-month period (December 1986 to March 1989), we encountered seven cases of ilioinguinal nerve entrapment following needle suspension procedures. In each case the diagnosis was made because of characteristic pain localized to the medial groin, mons, labia majora, and inner thigh. The intensity and character of the pain varied considerably, presumably depending on the time and degree of nerve compression. This paper discusses the resulting pain complex, diagnosis, pathophysiology, and options for prevention and treatment of this uncommon complication. PMID- 1635739 TI - Abnormal findings on hysterosalpingography: effects on fecundity in a donor insemination program using frozen semen. AB - OBJECTIVE: We sought to evaluate the effect of abnormal baseline hysterosalpingography (HSG) on subsequent fecundity during the first six cycles of treatment. METHODS: Hysterosalpingography was performed on 208 asymptomatic ovulatory women with no history of pelvic disease who were referred for donor insemination. The findings were categorized into five groups: 1) normal study, 2) uterine anomaly or filling defect with bilateral tubal patency, 3) normal uterine anatomy with unilateral tubal patency, 4) normal uterine anatomy with bilateral tubal blockage, and 5) normal uterine anatomy with hydrosalpinx. Subjects in groups 4 and 5 received inseminations only if patency of at least one fallopian tube was demonstrated with laparoscopy. Life-table analysis was performed to calculate the average monthly fecundity and cumulative conception rates for each group. The Mantel-Haenszel test was used to compare group fecundities. RESULTS: A total of 1460 donor insemination cycles were performed. The number of cycles in each group were as follows: group 1, 1173 (80%); group 2, 153 (10%); group 3, 90 (6.2%); group 4, 16 (1.1%); and group 5, 28 (1.9%). None of the patients in group 4 or 5 conceived. The cumulative conception rates in the first three groups were 46, 34, and 40%, respectively, and were not significantly different from one another (P greater than .05). Although a high incidence of uterine filling defects and unilateral tubal blockage was observed (19.2%), the incidence of an abnormal HSG finding that significantly decreased fecundity was only 2.8%. CONCLUSION: In women with no history of tubal or uterine disease, routine HSG before initiation of donor insemination is of limited value for identifying decreased treatment fecundity. PMID- 1635740 TI - Frequency, distribution, and theoretical mechanisms of hematologic and weight discordance in monochorionic twins. AB - OBJECTIVE: The purpose of this study was to determine the frequency, distribution, and most likely etiology of hematologic and weight discordance in pathologically proven monochorionic twins, and to use this information to reevaluate the neonatally derived definition of the twin-twin transfusion syndrome. METHODS: We reviewed our experience with 97 pathologically proven monochorionic twin pregnancies. The frequency and distribution of weight and hemoglobin-hematocrit (hb-hct) discordance were determined for all twin pairs. Factors that may have contributed to the discordance were identified, and theoretical mechanisms were proposed. RESULTS: All combinations of weight and hb hct discordance were observed. Thirty-four twin pairs (35%) were discordant for weight. In half of these (17 of 34), the hb and hct were concordant. In 18% (six of 34), the smaller twin had the higher hb-hct, and in 32% (11 of 34), the smaller twin had the lower hb-hct. Twenty-three of 63 size-concordant pairs (36%) were discordant for hb-hct. Ten infants were infected at birth, eight had malformations, and 25 likely suffered an acute transfusion event. CONCLUSIONS: Any combination of weight and hb-hct discordance can occur in monochorionic twins. Acute and chronic twin-twin transfusion, uteroplacental insufficiency, infection, malformations, or other factors may have accounted for the discordance observed. Thorough antenatal evaluation with invasive testing and marker studies (to identify a physiologically unbalanced placental anastomosis) may be necessary to establish an accurate diagnosis. We conclude that weight and/or hb-hct discordance is relatively common in monochorionic twins and in itself is not sufficient to diagnose twin-twin transfusion. PMID- 1635741 TI - The relationships among psychosocial profile, maternal size, and smoking in predicting fetal growth retardation. AB - OBJECTIVE: We explored the relationships among measures of psychosocial well being, maternal size, and smoking in predicting infant size at birth. METHODS: Participants in this population-based cohort study were drawn from public health prenatal clinics in Jefferson County, Alabama during 1985-1988. Para 1 and 2 women were screened for 11 risk factors for low birth weight, including small stature, a previous low birth weight infant, and smoking. RESULTS: Poor scores on five of six psychosocial scales, as well as on a combined profile, were associated with a significantly higher relative risk of fetal growth retardation (FGR) only in thinner women, defined as having a body mass index less than the median (relative risk [RR] 2.11, 95% confidence interval [CI] 1.47, 3.04). A significant association between the psychosocial profile and birth weight was demonstrated for thin women in a multivariate analysis adjusting for gestational age, race, infant sex, and smoking (P = .0003). The relationship remained significant when hypertension, alcohol and drug use, and weight gain were added to the model (P = .003). In women with a body mass index above the median, a poor psychosocial profile showed little association with FGR (RR 1.20, 95% CI 0.73, 1.98) and did not have a significant association with birth weight. A poor profile had a greater association with FGR in non-smokers (RR 2.04, 95% CI 1.29, 3.22) than in smokers (RR 1.4, 95% CI 0.95, 2.06). CONCLUSIONS: Greater pre pregnancy weight for height appears to protect against the adverse effects of a poor psychosocial profile in a population of poor, primarily black women. In thinner women, both smoking and a poor psychosocial profile were associated with a substantially increased rate of FGR, indicating a subgroup of women who may receive greater benefits from intervention programs. PMID- 1635742 TI - Subcutaneous tissue thickness cannot be used to distinguish abnormalities of fetal growth. AB - Two hundred forty-four women with normal pregnancies between 15-42 weeks' gestation served as a control group to determine subcutaneous tissue thickness at three different fetal locations: mid-calf, mid-thigh, and abdomen at the level of the abdominal circumference. The values at the three locations were comparable, varying between 1 mm at 15 weeks' gestation and approximately 5.5 mm at term. Similar measurements were obtained in two study groups consisting of 13 growth retarded and 38 large for gestational age fetuses. The degree of overlap in subcutaneous tissue thicknesses between the normal group and the two groups with disturbances in fetal growth was such that neither growth retardation nor macrosomia could be reliably predicted with these sonographic measurements. PMID- 1635743 TI - Doppler velocimetry in concordant and discordant twin gestations. AB - Doppler blood flow studies in 63 pairs of concordant and 17 pairs of discordant twins were compared with those of 277 appropriate for gestational age singleton fetuses. Discordancy was defined as a more than 20% intra-pair actual birth weight difference. The data were divided into five groups: singletons and large and small concordant and discordant twins. Statistical comparisons of the regression lines for the large concordant and discordant twins and the singletons showed no significant differences among the three lines, either in slopes (P = .1) or intercepts (P = .08). Comparisons of the regression lines for small concordant and discordant twins and the singletons indicated a significant interaction among the three lines (P = .01). Additional analysis leads us to conclude that the systolic-diastolic ratio (S/D) decreases with advancing gestational age for all groups except small discordant twins. The S/D of small discordant twins differed significantly from that of singletons and tended to differ from that of small concordant twins. PMID- 1635744 TI - Systolic or diastolic notch in uterine artery blood flow velocity waveforms in hypertensive pregnant patients: relationship to outcome. AB - To identify the relationship between a systolic or diastolic notch in uterine artery flow velocity waveforms and pregnancy outcome, we studied 140 hypertensive pregnant women with transvaginal, image-directed pulsed Doppler ultrasound. The subjects were classified according to the presence or absence of a systolic or diastolic notch. In 14 with a systolic and 25 with a diastolic notch, the resistance indexes in the uterine arteries on both sides of the uterus were significantly higher than in 101 subjects without a notch. Those with notches had significantly higher rates of fetal growth retardation and cesarean delivery because of fetal distress. Significantly more infants born to women with a notch spent longer than 48 hours in the neonatal intensive care unit. Subjects with a systolic notch also had significantly higher rates of abnormal fetal heart rate patterns during labor and low Apgar scores at 5 minutes. Fifty-one women with elevated resistances indexes in both uterine arteries were divided into two groups according to the resistance index in the umbilical artery. Each group was subdivided according to the presence or absence of a systolic or diastolic notch in the uterine artery flow velocity waveforms. In the group with a normal resistance index in the umbilical artery, five women had growth-retarded fetuses when a notch was present (N = 8), compared with none in women without a notch (N = 11) (P less than .005). The respective figures for the group with abnormal umbilical artery resistance indexes were 14 of 19 (73.7%) and two of 13 (15.4%) (P less than .002).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635745 TI - Oxygen measurements in endometrial and trophoblastic tissues during early pregnancy. AB - Placental and endometrial partial pressures of oxygen (PO2) were measured using a polarographic oxygen electrode during the first trimester of pregnancy. Between 8 10 weeks' gestation, placental PO2 levels were significantly lower (P less than .001) than endometrial levels. A significant (P less than .001) increase was observed for placental PO2 values measured at 12-13 weeks compared with those obtained at 8-10 weeks. We suggest that the increase of placental PO2 at the end of the first trimester is related to the establishment of continuous maternal blood flow in the intervillous space. PMID- 1635746 TI - Intravascular transfusion of fetuses with rhesus incompatibility: prediction of fetal outcome by changes in umbilical venous pressure. AB - OBJECTIVE: We examined whether abnormal elevations in umbilical venous pressure during intravascular transfusion predict post-transfusion mortality. METHODS: Umbilical venous pressures were measured during intravascular transfusion of human fetuses with Rhesus incompatibility. Five fetuses died within 24 hours after transfusion and nine fetuses survived the procedure. RESULTS: Survivors and non-survivors were similar in demographic and clinical data, as well as in transfusion characteristics. The only difference between the groups was the change in umbilical venous pressure during the transfusion: 5.0 +/- 6.3 mmHg for survivors versus 18.1 +/- 10.4 mmHg for non-survivors (P = .01). An increase in the umbilical venous pressure of 10 mmHg or more predicted fetal death with a sensitivity of 80% and specificity of 89%. CONCLUSION: Based on these results, we have modified our transfusion technique. If the change in umbilical venous pressure during intravascular transfusion approaches 10 mmHg, we discontinue the procedure. If the change in pressure exceeds 10 mmHg during transfusion, we remove blood and replace it with an equal volume of saline. PMID- 1635747 TI - Effects of norethisterone on pressor response to angiotensin II in men. AB - OBJECTIVE: We examined the effects of norethisterone and/or mestranol on the pressor response to angiotensin II in 20 healthy men. METHODS: Four study protocols were used: I) mestranol 0.08 mg/day for 6 days followed by mestranol plus norethisterone 20 mg/day for 6 days, II) mestranol 0.16 mg/day for 6 days followed by norethisterone alone 10 mg/day for 6 days, III) mestranol 0.24 mg/day followed by norethisterone 20 mg/day for 6 days, and IV) norethisterone 20 mg/day for 6 days. The angiotensin II dose to elicit a 20-mmHg rise in diastolic blood pressure was considered the effective pressor dose. This was determined before each protocol, at the end of the mestranol-alone portion, and at the end of the norethisterone portion. Subjects in study III also underwent measurement of plasma prostanoid levels, plasma renin activity and concentration, and estradiol and progesterone just before each angiotensin II infusion. Subjects in studies I and III underwent measurement of mean platelet volume, complete blood counts, liver function tests, and coagulation factors before each angiotensin II infusion. RESULTS: Whereas mestranol had no apparent effect on angiotensin II pressor response, norethisterone at a dose of 20 mg/day (with or without concurrent mestranol administration) caused a significant decrease in pressor responsiveness to angiotensin II. No changes in plasma prostanoids or renin could be found that would account for the change in pressor response. CONCLUSION: These findings indicate that the refractoriness to angiotensin II induced by norethisterone was related to its progestogenic properties. PMID- 1635748 TI - Fetal intracardiac potassium chloride injection to avoid the hopeless resuscitation of an abnormal abortus: I. Clinical issues. AB - OBJECTIVE: With the intention of preventing the attendant medical, ethical, and legal problems arising from the birth of live-born, anomalous fetuses, we initiated a program offering fetal intracardiac potassium chloride injection as an adjunctive measure in the setting of genetically indicated second-trimester abortion. METHODS: A lethal fetal injection was offered to patients carrying chromosomally or structurally abnormal fetuses at 19-24 weeks' gestation who desired abortion. When the patient elected this procedure, real-time ultrasound guidance was used to inject 3-5 mL of potassium chloride (2 mEq/mL) directly into the fetal cardiac chambers, followed by observation of fetal heart activity to ascertain cessation. Labor was subsequently induced with uterotonic prostaglandins. RESULTS: The procedure caused immediate cessation of fetal heart motion in 20 of 21 cases. There were no maternal complications. No fetuses were live-born. CONCLUSIONS: Direct fetal intracardiac potassium chloride injection effectively causes immediate fetal cardiac arrest. This approach may be adopted in cases of abortion by labor-induction methods at advanced gestations to ensure that the abortus is stillborn. PMID- 1635749 TI - The lesser tragedy. PMID- 1635750 TI - Prevention of neonatal group B streptococcal infections: advances in maternal vaccine development. AB - OBJECTIVE: We describe the current state of prevention of neonatal group B streptococcal infections and present recent advances toward the development of a maternal vaccine for prevention of this disease. DATA SOURCES: We used a MEDLINE search of the Index Medicus from 1976-1992 for articles regarding group B streptococcus classification and immunology. Group B streptococcus was also cross referenced with bacterial antigens, antibodies, and vaccines. Relevant textbooks were reviewed. METHODS OF STUDY SELECTION: Fifty-seven articles were selected as providing important background and new findings pertinent to this topic. DATA EXTRACTION AND SYNTHESIS: The literature supports prophylactic use of intrapartum antibiotics in mothers who are known carriers of group B streptococcus but highlights the need for more sensitive rapid screening techniques to identify this high-risk population. The promise of intravenous immunoglobulin for neonatal prophylaxis has not been borne out, although hyperimmune and monoclonal preparations offer renewed hope for prophylaxis and adjuvant therapy. Native bacterial polysaccharides, conjugated oligosaccharides and polysaccharides, and C proteins have been investigated as antigens for candidate vaccines. Antibodies elicited in human and animal studies provide protection against bacterial strains possessing these determinants. The theoretical existence of a "universal antigen" is significant because polysaccharide and C protein formulations are required to be polyvalent. CONCLUSIONS: The development of a vaccine for prevention of neonatal group B streptococcal sepsis is an attainable goal. Further study of the immunogenic properties of bacterial-cell-wall polysaccharides and their conjugates, C proteins, and the potential universal antigen is required. PMID- 1635751 TI - Fetal intracardiac potassium chloride injection to avoid the hopeless resuscitation of an abnormal abortus: II. Ethical issues. AB - Following the diagnosis of a genetic anomaly, some couples choose to have a legal abortion. However, following later abortions at greater than 20 weeks, the rare but catastrophic occurrence of live births can lead to fractious controversy over neonatal management. To avoid this situation, we have added fetal intracardiac potassium chloride injection to cause fetal cardiac arrest before induction of labor. The ethical issues surrounding such a practice are complex. We support this practice for three reasons: 1) The women's decision for abortion is protected because this practice assures her right for non-interference; 2) potential psychological harm to the patient and other family members is avoided; and 3) the potential for coercive intervention by other health care personnel is eliminated. At least three objections can be raised: 1) All abortions are unjust; 2) newborns and second-trimester fetuses at similar weights with identical defects should be managed in like fashion; and 3) the patient is not entitled to death of the fetus, only to evacuation of the uterine contents. On balance, we believe that our approach is justifiable ethically as it reduces the burden of conflict between the wishes of the patient and those of the neonatal care givers. It should be introduced only in situations in which the likelihood of civil or criminal liability or unwarranted medical intervention is high. PMID- 1635752 TI - Closed liability claims analysis and the medical record. AB - An analysis of 353 closed claims involving obstetrician-gynecologists revealed that the 40 highest-paid claims (11.3%) accounted for 88.7% of the total dollars spent. Newborn obstetrics, maternal obstetrics, and delayed-diagnosis claims represented 80%. Five doctors represented in the top 13 claims had another one or two claims among the highest 40. Only one of these physicians is still in good standing with the insurance company. Twelve claims (30%) were judged to be nonmeritorious, resulting in indemnity in five cases. Most of these claims illustrated either deficits with the medical record or system failures. A number of these problems could be prevented by avoiding system failures and by regarding the medical record as a legal document. Lawsuits occasionally resulted in an unfair distribution of dollars to injured parties and led to justifiable restriction of few physicians. It is critical that there be a record of why something was done. If the record is silent, there is no defense. An erroneous decision may be defensible if the reasons leading to it are recorded in the chart. PMID- 1635753 TI - Clues to enhancing the identification of human immunodeficiency virus-infected women. AB - Although ACOG recommends human immunodeficiency virus (HIV) testing of pregnant women who are "at increased risk" of HIV infection, more explicit recommendations do not exist. We suggest three stages of collecting clinical clues that may enhance the identification of HIV-infected women. The first considers traditional HIV-risk behaviors. The second incorporates the answers to specific questions in the clinical history, and the third considers the results of standard blood tests obtained during routine obstetric-gynecologic visits. PMID- 1635754 TI - Glenn A. Fry Award Lecture 1991: perceptual manifestations of imperfect optics in the human eye: attempts to correct for ocular chromatic aberration. AB - The profession of optometry has been very successful in providing optical corrections for spherocylindrical refractive errors. In this paper, I examine one attempt to improve retinal image quality beyond that afforded by a standard refractive correction. Ocular chromatic aberration is one of the factors that prevent retinal image quality from reaching the upper limit set by the wave nature of light. It can be subdivided into three primary aberrations (wavelength dependent differences in imaging plane, image position, and image size). We have been able to measure all three of these using psychophysical techniques. Although attempts to provide an optical correction for wavelength-dependent refractive errors have been optically successful, they have failed to improve vision. Several possible explanations are given for this failure. PMID- 1635755 TI - Cortical potentials evoked by short wavelength patterned light. AB - Pattern-evoked cortical potentials (PECPs) were recorded in response to the onset of blue and black, square wave gratings superimposed on a bright orange background. Several lines of evidence, including spectral sensitivity and the absence of response in a tritanopic subject, indicate that the measured cortical potentials reflect input from S cones. Spatial and temporal tuning of this response are comparable to psychophysical measures of the S-pathway. In agreement with previous studies of achromatic and chromatic spatial processing, a comparison of the response to patterns of different complexity indicates that spatial processing in the S-pathway can be described by linear systems analysis. An oblique effect for the S-pathway is demonstrated. Additional findings which bear on the nature of postreceptoral processing in the S-pathway are considered. Included are measurements from a patient with diabetic retinopathy. This study underscores the potential importance of the S-pathway for spatial information processing. PMID- 1635757 TI - Vergence errors: some hitherto unreported aspects of fixation disparity. AB - Measurement of the monocular components of fixation disparity indicated a higher prevalence of asymmetric contributions to the total deviation than previously reported. Furthermore, the exact proportion varied from moment to moment. Two of six subjects showed significant changes in fixation disparity over a period of 1 week. For all six subjects the changes in fixation deviation of one eye were virtually independent of those changes occurring in the other eye. In other words, these monocular variances were uncorrelated. Settings of the monocular components of binocular fixation disparity were accomplished at an accuracy close to that achieved by using a monocular vernier technique. The remaining differences appeared to be due to occasional instabilities during binocular viewing. The usual method of clinical measurement in which only one element is moved is not always equivalent to that determined by summing the two monocular components. The principal process measured by subjective fixation disparity appears to be either oculomotor or localized directional shifts of a monocular nature. PMID- 1635756 TI - Comparison of two glare measurement methods through light scattering modeling. AB - Two methods used for evaluation of glare in patients with opacities of the ocular media are compared. One is a low contrast letter test and the other is a direct light scattering meter. Theoretical expressions for the measures obtained from the two different glare tests are derived in terms of the point spread function. Measurements on healthy test persons wearing diffusive glasses with known light scattering properties were in good agreement with the theory. Data from 26 cataractous eyes are presented and discussed in light of the theory. PMID- 1635758 TI - Multimeridional apparent frontoparallel plane: relation between stimulus orientation angle and compensating tilt angle. AB - The classical apparent frontoparallel plane (AFPP) setting is typically obtained by having the subject move a series of parallel rods farther or closer until they line up in a plane perceived to be parallel to the face plane. If there is a size difference between the two ocular images, the AFPP setting defined by the rods will exhibit a tilt from the objective frontoparallel plane, about an axis parallel to the rods. The multimeridional apparent frontoparallel plane (MAFPP) is an extension of this procedure to rod orientations other than the vertical meridian. In previous studies, it was found that oblique tilt angle settings corresponding to rod orientations of 45 degrees and 135 degrees are equal to square root 2 times the tilt angle for the vertical rod orientation for the same interocular magnification difference along the meridian perpendicular to the rods. In this study, we measured the tilt angles produced by a series of oblique rod orientations between 15 degrees and 165 degrees, inclusive. Throughout the 150 degrees range tested, the tilt angles were found to be consistently proportional to the cosecant of the rod orientation angle, the factor square root 2 previously used being a specific example of this relation. Within this range, neither empirical cues nor the induced effect cause the cosecant relation to break down. It is suggested that the MAFPP procedure can be applied more extensively than previously anticipated. PMID- 1635759 TI - Monocular vernier acuity in normally binocular, monocular, and amblyopic subjects. AB - Previous experiments that have compared monocular vernier acuity in amblyopic, monocularly blind, and normal binocular subjects have been confined to the center of the retina. Based on brain changes that accompany the early disruption of form vision in one eye, monocularly blind subjects (that is, those who have completely lost the ability to process form vision in one eye) and amblyopic subjects are expected to have better vernier acuity in their normally functioning eye than subjects with normal binocular vision. Results from such studies have been ambiguous. This experiment was set up to study monocular vernier acuity in the central and peripheral retina of the three groups of subjects mentioned above. The results show that, at the center, monocularly blind subjects have the best vernier acuity followed by the amblyopic subjects and, finally, the normal binocular subjects have the worst acuity. In the peripheral retina, no significant differences were found between the three groups. A possible explanation has been provided for this finding. PMID- 1635760 TI - Accommodation on downward gaze. AB - A study was conducted with the purpose of examining the possible effects of vertical and horizontal eye movements upon accommodation. A special Badal stimulator was made which was vertically rotatable around the center of an eye. The stimulator was attached to the Three-Dimensional Optometer III (TDOIII), which could measure accommodation, eye movement, and pupil diameter simultaneously. The reliability of the TDOIII measurements of accommodation was checked by comparing with a stigmatoscope measurement. Three young males served as subjects. A small but definite near accommodation was measured dynamically in association with vertical eye movement. We believe this to be the first report of this finding. The amount of near accommodation with downgaze showed a tendency to decrease when the target was brought near. PMID- 1635761 TI - Normative data for hertel exophthalmometry in a normal adult black population. AB - Ocular protrusion data were obtained on 309 black adults using a Hertel exophthalmometer. The mean protrusion value for black men and women was 18.20 and 17.46 mm, respectively. The upper limit of normal was 24.14 and 22.74 mm for males and females, respectively. The differences between base measurement and mean protrusion values of black men and women were significantly different (p less than 0.015). These data are compared with those of adult white subjects and show that blacks have a higher range of normal than whites. The data indicate that the published upper limit of normal (21 mm) for exophthalmos is not appropriate for adult black patients. PMID- 1635762 TI - Acute ptosis secondary to contact lens wear. AB - Ocular ptosis secondary to the wearing of rigid contact lenses has been reported. Generally this ptosis is not of the classical variety, and appears to be an edematous or inflammatory response of the lid to the presence of the lens. We report a case of acute ptosis secondary to rigid lens wear in a patient who had undergone cataract surgery. The patient had been a contact lens wearer before surgery, and developed the relative ptosis postsurgically in the nonoperated eye. The ptosis resolved without any form of intervention other than ceasing to wear the contact lens. We feel that in cases where rigid lens wear is discontinued unilaterally for any reason, and a relative ptosis is noted, it should be given time to resolve before any therapeutic regimen is considered. PMID- 1635763 TI - Central retinal vein occlusion in a middle-aged adult with HIV infection. AB - Recently central retinal vein occlusion (CRVO) has been described as a possible AIDS-related phenomenon. We have seen another case of CRVO in a middle-aged male with HIV infection. Extensive laboratory testing failed to reveal any other systemic abnormality which might be contributory. The potential role of HIV infection in the pathogenesis of CRVO is discussed. PMID- 1635764 TI - Electronic submission of abstracts for the annual meeting of the American Academy of Optometry. AB - Recently the American Academy of Optometry conducted a 2-year trial in which abstracts submitted for presentation at the Annual Meeting could be transmitted to the Academy in electronic form. Electronic submission has many advantages for the author as well as for the Academy and therefore has now been endorsed as the preferred method of submission for future meetings. Step-by-step procedures for electronic submission are described. PMID- 1635766 TI - Future optometric educators. PMID- 1635765 TI - Low vision section. PMID- 1635767 TI - Measuring the effects of glare. PMID- 1635768 TI - [Combined coronary artery and heart valve surgery at the Clinic for Cardiovascular Surgery (1979-1990)]. AB - As a result of increasing mean age of patient undergoing open heart surgery more and more combined valve and coronary surgery cases are performed. The operative risk of combined procedure is higher than that of valve replacement or coronary bypass grafting alone. In case of aortic valve disease the operation reduces the workload of the left ventricle thus decreasing the oxygen demand of the myocardium. In pure mitral valve stenosis as a consequence of valve replacement the left ventricular preload increases and coexisting coronary artery disease is of greater importance than in the other case. Since 1979 until the end of 1990 there were 146 combined operations performed in the Cardiovascular Surgical Clinic of Semmelweis Medical University of Budapest. The operative results and theoretical considerations are discussed. PMID- 1635769 TI - [Surgical cerclage in the treatment of cervical incompetence during pregnancy (determining the legitimacy of the procedure)]. AB - The authors studied the effectiveness of the cervical cerclage operation in the therapy of cervical insufficiency during the pregnancy. Two Hundred sixteen pregnant women took part in this trial in whose pregnancy the necessity of cerclage operation was not unequivocal. It means, that the therapeutical cerclage operation was not necessary, but the necessity of prophylactic cerclage operation was doubtful as well. From the randomized 216 cases they performed cerclage operation in 108 pregnancies and in 108 cases they did not perform it. In the respect of pregnancy care they did not make any difference between the two groups. The authors from their trial draw the conclusion, that in doubtful cases where the necessity of cervical cerclage operation is not unequivocal--e.g. at serious gestational case history--it is advisable to perform the operation. The danger of premature birth can be diminished in this way. PMID- 1635770 TI - [Reconstruction of the mandible using a vascularized graft from the iliac bone]. AB - Twelve vascularized iliac crest free-tissue transfers were used for oromandibular reconstruction, 2 as osteocutaneous and 10 as osseous flaps. Two patients had preoperative radiotherapy. Nine of the 12 reconstruction were carried out primarily, following radical surgery for oral cancer. One graft was lost by venous thrombosis. Evidence of bone union was noted in 11 patients, and no pseudoarthrosis was observed. The main advantage of this method is the availability of a large bloc of living composite tissue and both the functional and cosmetic results should be improved in patients undergoing resection of the anterior part of the mandible. PMID- 1635771 TI - [Activities of the Hungarian Medical Student Association]. PMID- 1635772 TI - [Reasec poisoning in childhood]. PMID- 1635774 TI - [Clinical significance of serological markers of Helicobacter pylori]. AB - Helicobacter pylori (H. pylori) is a Gram-negative, curved bacillus known since 1983. It is supposed to play role in the pathogenesis of certain gastroduodenic diseases, e.g. non-ulcer dyspepsia (NUD), chronic inflammation, ulcers, etc. Serum samples of 70 patients who were examined for stomach complaints with gastroscopy and those of 22 healthy persons were analysed. The purpose of the study was to evaluate anti-H. pylori IgG, IgM and IgA antibodies using ELISA method. Whether the antibodies can be detected or not, 8 possible variations exist, each of them denoting certain state of infection. These states are not always going parallel with the macroscopic pictures revealed by gastroscopy, but there are some obvious congruences. Results show that serologic examination cannot replace gastroscopy but on the other hand in follow-up tests and examinations as well as in understanding the aetiology of different gastroduodenal diseases it can play an important role. PMID- 1635775 TI - [Clinical significance of intrauterine growth retardation]. AB - The authors have examined the measure of the influence of the proportional and disproportional retardation on the results of the pre- and subnatal observation of the fetus and on the frequency of perinatal mortality and newborns' morbidity, premature birth and newborns born with low birth weight. The authors have stated the two types of retardation leads to a higher global perinatal mortality mainly by causing a more frequent intrauterine mortality. Comparing the results of the retarded newborns to those of the somatically normally developed neonates they prove it from several aspects that the proportional retardation means a much higher risk for the newborn than the disproportional retardation which is also a risk factor. The new NDN classification system elaborated and used by the authors is suitable for differing the two types of retarded newborns. PMID- 1635773 TI - [Genetic traits in the area of Bodrogkoz]. AB - In 1984 a late malaria endemic area, called Bodrogkoz was studied. This was a reexamination of the population genetic work performed by Walter, Nemeskeri. In six villages of Bodrogkoz 328 persons were tested for AB0, Rh blood groups, haptoglobins, haemoglobin concentration, haematocrit, erythrocyte amount, the MCV, the MCH and the G-6-PD were analyzed. The quantitative determination of HbF and HbA2, red cell osmotic resistance and thalassemia were measured as well. Thalassemia heterozygote carriers and an increased level of HbF were revealed. The frequency of G-6-PD deficiency was 0.39%. In Bodrogkoz the frequencies of AB0, Rh and haptoglobin types were similar in the present and all previous studies. The background of this similarity might be the genetic similarity between two following generations. On the basis of these facts, the Hb0 Arab and partially DNA work we suggested an alternative hypothesis that these mutant genes got into Bodrogkoz by the rather later migration than with ancient Hungarian people during the period of conquest of Hungary. PMID- 1635776 TI - [Successful surgical correction of persistent truncus arteriosus by an aortic homograft]. AB - After palliative procedure a 2 years old girl with congenital heart disease was corrected with aortic homograft. Truncus arteriosus is a rare congenital heart disease and this is the first successfully corrected case in our country. Using homograft in this age group improves the early and late result of this type of corrective surgery. PMID- 1635777 TI - [Doege-Potter syndrome. Fibrous mesothelioma of multicentric localization, causing hypoglycemia]. AB - The authors present a case of a 73 year old female patient. She had a left side pleural mesothelioma and had been operated thrice. At the third operation an abdominal propagation joined to the thoracic mesothelioma. Starting from this third surgery severe hypoglycemic episodes illustrated the clinical pictures. The electronmicroscopy of the resected tumor mass documented the presence of neurosecretory granules. This strongly suggests that tumor mass produced a substance which could have been responsible for the hypoglycemic episodes. Due to the fact the insulin levels measured during severe hypoglycemias were always on a low level, we suppose that an insulin like material (IGF--II) was responsible for the above mentioned symptoms. The authors briefly review the literature. PMID- 1635778 TI - [Activities of the Medical Section of the Transylvanian Museum Association]. PMID- 1635780 TI - [The non-ulcer dyspepsia syndrome]. PMID- 1635779 TI - [Jozsef Sadler, physician-botanist in the first half of the 19th century]. PMID- 1635781 TI - The Prescription Accountability and Patient Care Improvement Act: issues of concern for oncology nurses. PMID- 1635782 TI - [The Nutrition Committee of the Austrian Society of Pediatrics and Adolescent Medicine. Comment on nutrition with solid foods in infancy and early childhood]. AB - The Nutrition Committee of the Austrian Pediatric Society recommends that weaning foods should be introduced between 4 and 6 months of age, which agrees with the recommendations in the EC and the U.S. Opinion against early introduction of solid foods have focused on concerns about renal solute load, obesity, coeliac disease, and food allergy. On the other hand, when weaning was postponed after 6 months of age, growth faltering in some breastfed infants and iron-deficiency anemia in infants fed non-fortified formulas or cow's milk were observed. Two broad categories--"baby foods" and "cereal-based weaning foods"--are on the market in Austria. "Baby foods" include complete meals sold in jars, soups, desserts and puddings, fruit juices, nectars, and vegetable juices. "Cereal-based weaning foods" are composed of one or more cereals either alone, or with the addition of vegetables, fruits, milk and milk products, egg, or other ingredients. Weaning food labelling should include information if sugars, salt, iron, vitamins minerals and trace elements have been added and if the product is free from gluten, cow's milk and egg protein, and lactose. PMID- 1635783 TI - Epidemiological aspects of childhood diabetes mellitus. AB - Descriptive epidemiological studies concerning childhood IDDM have demonstrated geographic differences and an increase in incidence rates. While sex and age distribution have been found remarkably similar. PMID- 1635784 TI - IDDM in Hungarian children: population-based clinical characteristic and their possible implication for diabetic health care. Hungarian Childhood Diabetes Epidemiology Study Group. AB - Following our 10-year retrospective study, prospective registration of all newly diagnosed children has started in 1989. Data of the primary source (hospital records) were validated using the central pharmacy register for insulin. Ascertainment rate was 96%. Clinical characteristics are analysed on the basis of data of 324 children diagnosed in 1989-1990. There were some regional differences in incidence with no relationship between incidence and the degree of urbanization. The duration of clinical symptoms before diagnosis was less than two months in 81% of the cases, two to four months in 17% of the children, and no symptoms were recorded in 2% of the cases. The mean reported weight loss was 3.3 kg (range 0 to 16 kg), blood glucose at diagnosis ranged between 8.5 and 80.0 mmol/l (mean 25.4 mmol/l). Ketosis was noted in 86%, and 40% received infusion therapy at onset. There was no correlation between age, initial, blood glucose, ketosis, severity of the clinical condition and duration of symptoms. IDDM was reported in 4.7% of first degree relatives. Birth order was a significant risk factor, firstborn children were less at risk than subsequent siblings (P less than 0.05); the number of children in diabetic families was similar to those in the general population (2.1 vs. 1.8). The high mean blood glucose and ketosis indicate a relatively severe metabolic decompensation at the time of diagnosis and call for further improvement in the diagnostic acumen of the pediatric community. PMID- 1635785 TI - [Incidence of pediatric diabetes mellitus in Austria--results of a prospective study 1989-1990]. AB - The mean annual incidence of childhood diabetes mellitus (0-14 years of age) in Austria was 7,713 cases per 100,000 during 1989-1990. The manifestation rate in boys was insignificantly higher than in girls and the age distribution showed an increase up to an incidence peak around puberty. Typical seasonal variation with the highest incidence in autumn and winter could be demonstrated and the incidence in eastern parts of Austria seemed to be higher than in Vorarlberg. PMID- 1635786 TI - Risk factors for cardiovascular disease in chronic spinal cord injury patients. AB - To establish whether the reported increased cardiovascular (CV) morbidity in spinal cord injury (SCI) patients is due to increased levels of established CV risk factors, we assessed overall CV risk in 102 consecutive patients aged 25-64 by calculation of a 'risk factor score' (RFS) derived from the MRFIT study (age, diastolic blood pressure (DBP), total cholesterol (TC) level, cigarettes/day, sex), obtaining a percentile position amongst an age and sex matched peer group from the 1983 Australian Risk Factor Prevalence Study. Chronic SCI patients had a very low overall percentile position of risk of 26.03 + 15.06 (mean +/- S.D.) and those patients with SCI for greater than 10 years had only a slightly higher risk position of 33.16 +/- 29.66. The low relative risk in SCI patients was due mainly to significantly lower DBP levels (67 +/- 13 mm hg), as TC levels (5.38 +/- 1.60 mmol/L) and cigarette consumption (31% smokers, mode 11-20/day) were similar to the control population (83 +/- 12 mmHg, 5.68 +/- 1.2 mmol/L, 28% smokers, mode 11 20/day, respectively). As other known risk factors such as lipoprotein cholesterol fractions were not included in the RFS index, these were measured in 327 consecutive SCI patients. HDL cholesterol levels, which are negatively correlated with CV risk, were significantly lower in SCI patients (1.12 +/- 0.30 mmol/L) compared to controls (1.35 +/- 0.35 mmol/L) and those patients more than 10 years post SCI had still lower levels (1.02 +/- 0.40). These data suggest that the reported increased incidence of CV disease in SCI patients is unexplained by increases in BP, TC or smoking. However, low HDL levels may contribute to CV risk and the role of other risk factors such as increased vascular reactivity remain to be established. PMID- 1635787 TI - The role of the diaphragm in trunk extension in tetraplegia. AB - Interest has been focused on the diaphragm as the all important respiratory muscle in tetraplegia for decades but its unique role as a trunk extension muscle has not been considered. This study set out to establish the relationship, if any, between the roles of the diaphragm during arm exercise and trunk flexion. Eight male complete cervical cord injuries (CCI) patients, sitting in their wheelchairs, were studied during rest, trunk flexion and start of arm cranking. The average flow, volume, oesophageal and gastric pressures (Poes and Pga) and the myoelectric activity of the diaphragm (EMGdi) were recorded. The EMGdi pattern changed from phasic activity at rest to continuous or almost continuous activity during trunk flexion. Patients were then either spontaneously holding their breath or breathing irregularly with rapid or shallow breaths. Also, the normalised EMGdi signal strength increased by an average of 150% and the mean Pga by about 3 kPa, while mean Poes decreased by about 0.5 kPa. At the start of exercise, patients with poor triceps function, less than MRC grade 3, exhibited similar ventilatory and EMGdi changes as had been seen in trunk flexion. In patients with better triceps function, only minor changes in these variables were observed. The findings suggest that the diaphragm acts both as a trunk extensor muscle and a respiratory muscle. During posture imbalance, the postural needs temporarily override the respiratory needs. PMID- 1635788 TI - The neurosensory musculocutaneous tensor fasciae latae flap: long term results. AB - In 1971 we started covering pressure sores and unstable scars with transposition rotation-muscle and musculocutaneous flaps. In 1980 we published the first results with 6 neurosensory musculocutaneous tensor fasciae latae flaps. Until April 1989, 31 tensor fasciae latae flaps (TFL) were used, and we review a consecutive series of 19 neurosensory TFL-flaps. Questions such as whether to delay the procedure; early and late complications; evolution of the sensation; and indications are outlined under the aspects of long term follow up studies. The conclusion is that if the neurological pattern permits a neurosensory flap, such flaps should be done because no local recurrence occurred. In extended neurosensory TFL-flaps sensation of the filling status of the rectum is improved, and sitting control and perception of the 'body scheme' are also improved. PMID- 1635789 TI - Changes in thyroid hormones, thyroid stimulating hormone and cortisol in acute spinal cord injury. AB - To determine the hormonal response to acute spinal cord injury, serial serum samples were collected from 18 patients with acute spinal cord injury and from 14 control patients with spinal fractures without cord injury. The first sample was taken within 24 hours of injury, the second at 24-48 hours; and the third at 7 days for determination of thyroxine (T4), free T4 (FT4), triiodothyronine (T3), reverse T3 (rT3), T3 uptake (T3U), thyroid stimulating hormone (TSH), thyroxine binding globulin (TBG), growth hormone (GH), cortisol, and insulin. Significant increases were observed in rT3 levels and transient changes were observed in the T4 and T3 levels in the spinal cord injured group but not in the group with spinal fractures alone. The changes in the spinal cord injured patients are consistent with the 'low T3 syndrome'. However, the persisting rise of rT3 at 7 days was an unexpected finding. In addition to the cord injury, these changes may also be related to dexamthasone administration and nutritional factors. PMID- 1635790 TI - The effects of sauna on tetraplegic and paraplegic subjects. AB - Six tetraplegic (T) and 4 paraplegic (P) subjects underwent a 20-minute pre sauna phase (30 degrees C DB; 65% RH), and an up to 15-minute sauna (85 degrees C DB; less than 10% RH), followed by a 15 minute post sauna phase (30 degrees C DB; 65% RH). During all phases subjects wore a bathing suit and remained supine on a hospital trolley. Heart rate (HR) and blood pressure (BP) were recorded during all phases. Rectal temperature (Trec) was measured by a probe (AD590) inserted approximately 14 cm into the rectum. Oral temperature (Toral) also utilising (AD590) circuitry was recorded simultaneously with Trec. Skin temperature (Tsk) (AD590) was measured on the head, chest, right thigh and right calf. Forehead sweat rate (SR) was determined from dew point temperature (Tdp). A catheter was inserted into a dorsal hand or foot vein and venous blood was withdrawn at selected times and analysed for haemoglobin (Hb) and haematocrit (Hct), and the separated plasma was analysed for glucose (Glu), sodium (Na+), potassium (K+) and chloride (C1-). Venous blood sampled just prior to entering and just prior to leaving the sauna, was analysed for adrenalin (A) and noradrenalin (NA) using high performance liquid chromatography. For both groups HR rose significantly during the sauna with a significant decline in HR for the P group during the post sauna phase. There were no significant changes in systolic BP for either group. A significant decline in diastolic BP was found for the T group during the post sauna phase. There were no episodes of syncope.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635791 TI - Vocational decision making by sixty spinal cord injury patients. AB - Sixty persons with spinal cord injury completed the My Vocational Situation (MVS) questionnaire developed by Holland, Daiger and Power. The MVS was designed to identify problems related to vocational decision making, ie lack of vocational identity, lack of occupational information, and the presence of environmental or personal barriers to a chosen occupational goal. As expected, more problems were reported by unemployed persons than by employed persons, and by those who reported lower levels of psychological well being. MVS scores were not mediated by age, time since injury or severity of injury. PMID- 1635792 TI - Psychological approach to the rehabilitation of the spinal cord injured: the contribution of relaxation techniques. AB - We analyse the benefit of learning relaxation techniques as an essential coping strategy in the behavioural medicine field. This has proved useful as a part of the newly spinal cord injured rehabilitation treatment or concerning later problems if there is readmission. We report the changes we have made in the relaxation standard methods to be used in spinal cord injured patients as well as the timing in the rehabilitation process when these techniques were applied. PMID- 1635793 TI - Aerobic power of competitive paraplegic road racers. AB - The purpose of this study was to determine peak aerobic power and associated physiological responses in highly competitive spinal cord injured (SCI) paraplegic road racers. Seven (6 male and one female) active paraplegic (lesions T4-T12) road racers and 9 healthy untrained able-bodied males performed continuous graded arm crank ergometer tests to exhaustion for determinations of peak power output (PO), oxygen uptake (VO2), pulmonary ventilation (VE), heart rate (HR), and respiratory exchange ratio (RER). Compared to able-bodied subjects, male paraplegic road racers elicited significantly (p less than or equal to .05) higher mean (+/- SD) peak levels of PO (141.6 +/- 8.8 vs 111.4 +/- 27.7 W), absolute VO2 (2.72 +/- .52 vs 2.22 +/- .381/min), and VO2 per unit of body weight (43.06 +/- 7.4 vs 30.33 +/- 4.3 ml/kg/min). Although peak HR (180.3 +/- 9.5 vs 173.2 +/- 8.5 bpm) and VE (92.8 +/- 17.2 vs 74.6 +/- 20.3 l/min) tended to be higher for male paraplegic road racers than able-bodied subjects, the differences were not statistically significant. The female paraplegic road racer achieved the highest peak levels of PO (119 W) and VO2 (1.99 l/min; 38.0 ml/kg/min) reported to date for wheelchair-dependent women. These data suggest that intense physical training via wheelchair propulsion can markedly enhance upper body cardiovascular fitness in SCI paraplegics. However, the correlational analysis between 10 km time and peak VO2 was nonsignificant (p greater than .05) indicating that factors other than peak upper body aerobic power may influence wheelchair road racing performance. PMID- 1635794 TI - The value of urodynamics and bladder management in predicting upper urinary tract complications in male spinal cord injury patients. AB - A review of 160 male patients admitted to the Shepherd Spinal Center was completed to determine the influence of urodynamic findings and choice of bladder management program on the risk of developing upper urinary tract distress following acute spinal injury. Within the context of this investigation, upper urinary tract distress was defined as presence of hydronephrosis, febrile urinary tract infection, urolithasis or vesicoureteral reflux. Three groups were identified according to the urodynamic findings and the bladder management program. Thirty-four subjects with preservation of detrusor function managed their bladders by spontaneous voiding. Seventy patients with detrusor areflexia managed their bladders via intermittent catheterization; and 56 males who had detrusor hyperreflexia on urodynamics were managed by a reflex voiding program with condom drainage. None of the subjects with preservation of spontaneous voiding function experienced upper tract distress. Seven percent of those on intermittent catheterization and 32% of those managed by a reflex voiding program experienced upper tract distress. The presence of detrusor hyperreflexia with or without vesicosphincter dyssynergia influenced the likelihood that subjects would experience upper urinary tract distress following spinal injury. While traditional urodynamics failed to distinguish patients managed by a reflex voiding program who experienced upper tract distress from those who did not, calculation of a new urodynamic variable, the urethral pressure gradient, was found to assist in this prediction. PMID- 1635795 TI - Spinal cord lesion after penicillin gluteal injection. AB - Penicillin gluteal injection may cause sudden and irreversible paraplegia. In the literature 6 cases have been reported, and spinal infarction was conjectured, the mechanism being obscure. The actual incidence of such a complication is not known. We observed 2 more cases, 6 and 16 years respectively following such an injection. The clinical features suggested that spinal infarction had occurred, and an MRI study in the most severely impaired patient showed marked spinal atrophy, giving further support to the spinal infarction hypothesis. These findings and the pathophysiological considerations suggest that the mechanism might be the accidental injection into the superior gluteal artery, causing its distal spasm and the upstream ascent of the penicillin with ensuing embolic and/or spastic occlusion of the arterior spinal artery. PMID- 1635796 TI - Acute paraplegia resulting from haemorrhage into a spinal neurofibroma. AB - Acute paraplegia due to the intratumour haemorrhage of spinal neurofibroma is a rare condition. We describe 2 patients with this unusual presentation. Surgical treatment was successful in both patients. These 2 cases are reported, and the literature is reviewed. PMID- 1635797 TI - Esophageal perforation: a delayed complication following traumatic spinal cord injury. Case report. AB - Esophageal perforation is an uncommon but serious complication of penetrating injuries to the neck and chest. A case of delayed esophageal perforation in a patient with traumatic spinal cord injury is presented. The pathophysiology, diagnosis, and treatment of this potentially fatal complication are discussed. PMID- 1635799 TI - Pediatric neurology. PMID- 1635798 TI - Neurocutaneous syndromes. AB - Many of the neurocutaneous disorders are more common than once suspected, in part because patients with milder forms of the disorders are now more likely to be recognized. Improved diagnostic studies and increasingly specific medical and surgical therapy allow some previously untreatable complications to be successfully managed. Genetic linkage analysis has localized the abnormal gene for some of the hereditary neurocutaneous disorders onto specific chromosomes, and newly developed clinical diagnostic criteria have improved our ability to establish a definite diagnosis in less obvious patients. Thus, the outlook for these patients is no longer uniformly pessimistic. PMID- 1635800 TI - Perinatal cerebrovascular disease in the neonate. Parenchymal ischemic lesions in term and preterm infants. AB - Acute cerebrovascular injury in term and preterm infants is a cause of significant morbidity. Treatment efforts in the past have focused on attempts to prevent such injury by interceding during labor in term infants and improving neonatal care in preterm infants. Epidemiologic studies suggest that these strategies have had little impact. A new strategy--drug treatment of acute ischemic brain injury--is on the horizon. The recognition and prognostication in ischemic neonatal brain injury takes on a new importance in this light. PMID- 1635801 TI - Bacterial meningitis in children. Selected aspects. AB - Accumulating clinical experience has gradually outlined the epidemiology of acute bacterial meningitis, including the epidemic and the sporadic forms, the customary clinical signs related to different age groups and causative organisms, and methods of rapid diagnosis by laboratory examinations. Effective treatment, which continues to evolve, emerged in the 1940s with the development of antibacterial antimicrobials, first with the sulfonamides and then with the penicillins. The literature relative to these aspects of the disease has been abundant in the past few years. This article is directed to a variety of topics that have direct bearing on the disorder but are less often addressed to those who deal with infants and children. PMID- 1635802 TI - Acquired immunodeficiency syndrome and the child's central nervous system. AB - Human immunodeficiency virus-1 (HIV-1) associated central nervous system disease may complicate the course of HIV-1 infection in infants and children. Neurologic dysfunction in these young patients adds significantly to the morbidity of the disease and is often a devastating complication. It is apparent that HIV-1 infection in infants and young children is complicated by numerous developmental parameters. The developmental stage of the nervous and immune systems when exposed to the virus is likely to interact in complex ways with HIV-1 variables. In order to care for these children and to design rational approaches for treatment and prevention, it is now critical to develop a better understanding of how HIV-1 affects the developing nervous system. PMID- 1635803 TI - Nonepileptic paroxysmal events in childhood. AB - Seizures are the most commonly occurring paroxysmal events of childhood. There are a large number of other disorders, however, that present with discrete attacks separated by symptom-free intervals. The differentiation of these conditions from seizures depends on a willingness to consider alternate diagnoses and a thorough review of the history of the events. Laboratory tests, and especially the electroencephalogram, are aids to diagnosis, but reliance on laboratory data has many pitfalls. The clinical features of the important nonepileptic paroxysmal disorders of childhood are reviewed. PMID- 1635804 TI - Movement disorders of children. AB - Abnormal movements occur in many of the neurologic disorders affecting children and in certain conditions are the presenting major manifestations. In children abnormal movements may be transient and benign and do not necessarily indicate a progressive degeneration of the central nervous system. Clinical observations and appropriate laboratory investigation will frequently lead to a neurologic diagnosis that in many instances will respond to specific pharmacologic treatment. PMID- 1635805 TI - Imaging of the central nervous system in pediatrics and adolescence. AB - Magnetic resonance imaging (MRI) has taken its place beside computed tomography (CT) and ultrasonography in effective imaging of the central nervous system in infants and children. The major initial impact of MRI in pediatric neuroradiology has been the displacement or replacement of the more expensive and invasive procedures such as angiography, myelography, cisternography, and ventriculography. Ultrasonography remains the screening procedure for fetal and infant central nervous system abnormalities, whereas CT continues to be an effective brain screening technique after loss of the ultrasonography windows with growth of the child. The better the clinical information transmitted to the radiologist in advance of imaging of the patient, the more likely the clinician will receive valuable information in return. PMID- 1635806 TI - Functional brain imaging in pediatrics. AB - With the development of noninvasive tomographic imaging techniques, it is now possible to measure local chemical and physiologic functions in various body organs. Studies of local cerebral glucose metabolism in infants and children using positron emission tomography (PET) have provided important information on human brain functional development and plasticity. The clinical application of functional neuroimaging techniques in the management of pediatric neurologic disorders has yielded encouraging results. In children with intractable epilepsy being considered for surgical intervention, PET is highly sensitive in localizing focal areas of cortical dysplasia, heterotopias, and other migrational defects corresponding to surface electrographic localization of epileptogenic regions. Expanding PET technology provides a new approach that holds great promise in the diagnosis and management of brain disorders in children. PMID- 1635807 TI - Detection of inherited neurometabolic disorders. A practical clinical approach. AB - The most common neurometabolic disorders to be considered are organic acidurias and amino acid apathies followed by urea cycle disorders, congenital lactic acidosis, peroxisomal disorders, and, less frequently, sphingolipidoses, mucopolysaccharidoses, glycoprotein degradation disorders, fatty acid oxidation disorders, and neuronal ceroid lipofuscinoses. PMID- 1635808 TI - Rhabdomyolysis in childhood. A primer on normal muscle function and selected metabolic myopathies characterized by disordered energy production. AB - Patients with rhabdomyolysis present an important clinical problem. In acute episodes immediate treatment may be necessary to prevent significant morbidity and mortality. Evaluation of affected patients necessitates an understanding of basic muscle pathophysiology and of the variety of disturbances that can interfere with muscle energy metabolism. The physician must then pursue a systematic stepwise evaluation (Table 6) that includes obtaining relevant history and laboratory studies, as well as arranging for appropriate provocative testing and muscle biopsy. Once the diagnosis is established, patient and family counseling is necessary, particularly in genetic disorders. Unfortunately, specific therapies have not proven entirely successful, and treatment generally has been directed at reducing the severity of rhabdomyolytic episodes. PMID- 1635809 TI - Changes in the approach to central nervous system tumors in childhood. AB - Current approaches to children with brain tumors are in a state of evolution. Currently, 50% of children with all types of brain tumors may be expected to survive 5 years. Therefore, the goals of neuro-oncology have broadened to include improved survival and improved quality of life. This article reviews changes in therapy that have altered survival as well as changes in therapy as a consequence of increasing recognition of complications and toxicity of treatment. PMID- 1635810 TI - Current status of Duchenne muscular dystrophy. AB - Duchenne muscular dystrophy is the second most common lethal genetic disorder in humans. With the advent of molecular genetic technology, the definition of this disease has been modified to include an abnormality of dystrophin in muscle--a dystrophinopathy. Accurate genetic counseling is possible using methods of deletion detection and linkage analysis. Treatment of this type of muscular dystrophy may soon mean the routine use of steroids and later include direct injection of an artificial gene for dystrophin. PMID- 1635811 TI - A practical approach to children failing in school. AB - The most likely causes of failure in school in otherwise capable children who come from homes in which they are loved and cared for are learning disabilities, affective illness, primary disorder of vigilance and, on occasion, narcolepsy. The various learning disabilities are often accompanied by problems of attention, concentration, organization, mood and feelings, and social interaction. These latter problems are reflections of biochemical disorders that respond effectively to judicious pharmacologic intervention. When this type of medical management is combined with constructive counseling and suitable curriculum adjustments, the child can attain his or her maximum education potential and become a productive and contributing adult member of society. PMID- 1635812 TI - Evaluation of the child with idiopathic mental retardation. AB - A review of the advances in diagnostic techniques for evaluation of children with idiopathic mental retardation is presented. The current status of the use of clinical genetics, cytogenetics, molecular genetics, and neuroimaging in evaluating children with mental retardation is emphasized. Special attention is given to the evaluation of children with mental retardation and "autism" or "cerebral palsy." PMID- 1635813 TI - Metabolism of 3,5,3'-triiodothyronine sulfate by tissues of the fetal rat: a consideration of the role of desulfation of 3,5,3'-triiodothyronine sulfate as a source of T3. AB - We have recently demonstrated that serum concentration of 3,5,3'-triiodothyronine sulfate (T3S) is markedly elevated in the human newborn at a time when serum 3,5,3'-triiodothyronine (T3) is very low. The present study explores the ability of maternal (19-21 d pregnant) and near-term fetal Sprague-Dawley rat tissues to 1) monodeiodinate T3S and T3 in both the outer and the inner ring and 2) desulfate T3S to T3. Maternal liver microsomes metabolized T3S exceedingly efficiently (compare fetus p less than 0.05). Eighty percent or more of T3S was consumed during its incubation with 360 micrograms/mL microsomes for 2 h. The majority of the consumption of T3S by adult liver microsomes occurred by its 5' monodeiodination to I-; little inner-ring monodeiodination to 3,3' diiodothyronine was demonstrable. In fetal liver microsomes, however, over 75% of the substrate T3S remained unchanged after a 2-h incubation. T3 was metabolized similarly moderately by fetal and maternal liver microsomes. Brain microsomes metabolized T3S poorly in both the mother and the fetus. Over 90% of substrate T3S remained unchanged after a 2-h incubation in each case. Interestingly, brain microsomes metabolized T3 more rapidly than T3S (p less than 0.05). In the fetus, desulfation of T3S to T3 was clearly evident only in microsomes from the liver and the brain; in the adult, it was plentiful in many tissues. Fetal liver and brain tissues metabolize T3S poorly, and both actively desulfate T3S to T3. These data and those indicating high serum T3S in the fetus suggest that T3S is a local source of T3 in critical tissues in the fetus and possibly in adults with the low T3 syndrome. PMID- 1635814 TI - Urinary medium-chain acylcarnitines in medium-chain acyl-CoA dehydrogenase deficiency, medium-chain triglyceride feeding and valproic acid therapy: sensitivity and specificity of the radioisotopic exchange/high performance liquid chromatography method. AB - To determine the sensitivity and specificity of detecting urinary medium-chain acylcarnitines for the diagnosis of MCAD deficiency, 114 urine specimens from 75 children with metabolic diseases and controls were analyzed in a blinded fashion using a radioisotopic exchange/HPLC method. All 47 patients with MCAD deficiency were correctly diagnosed using the criterion hexanoylcarnitine or octanoylcarnitine peak areas larger than those of other medium-chain acylcarnitines. The majority of them were tested during the asymptomatic state without L-carnitine loading. Four patients with other defects of fatty acid oxidation and three patients receiving valproic acid had a similar acylcarnitine excretion pattern. To further examine the specificity of the method, eight infants receiving a diet enriched with medium-chain triglycerides and 13 additional patients receiving valproic acid were studied. Most of these also tested positive for MCAD deficiency by the above criterion. Analysis by a new gas chromatographic-mass spectrometric procedure revealed that octanoylcarnitine, not valproylcarnitine, was the most abundant medium-chain carnitine ester excreted by a patient treated with valproic acid. Quantitation of urinary hexanoylcarnitine and octanoylcarnitine showed considerable overlap among patients with MCAD deficiency and those receiving valproic acid or a medium-chain triglyceride enriched diet. MCAD deficiency can be reliably detected in urine specimens by this method without the need for prior carnitine loading. However, other defects in fatty acid oxidation must be differentiated from MCAD deficiency, and a history of medium-chain triglyceride or valproic acid administration must be considered if the diagnosis of MCAD deficiency is sought through analysis of urinary acylcarnitines. PMID- 1635815 TI - Short-chain acyl-coenzyme A dehydrogenase activity, antigen, and biosynthesis are absent in the BALB/cByJ mouse. AB - BALB/cByJ (J) mice have short-chain acyl-CoA dehydrogenase (SCAD) deficiency and an organic aciduria similar to that of human SCAD deficiency. [9,10(n)-3H]- and [15,16(n)-3H]palmitate oxidations in J mouse fibroblasts were 96 and 35% of control, respectively, consistent with an isolated SCAD defect. Acyl-CoA dehydrogenase activities were assayed in muscle and fibroblast mitochondria from BALB/cBy controls (Y) and SCAD-deficient J mice. Medium-chain acyl-CoA dehydrogenase (MCAD) activities were comparable in both J and Y mice from all tissues. In the presence of MCAD antiserum, SCAD activities in J mice were undetectable in both tissues. Apparent Km and Vmax values in liver mitochondria suggested a somewhat increased affinity of MCAD for butyryl-CoA in J mice, as compared with MCAD from other species. Immunoblot studies using mitochondria revealed identical apparent SCAD molecular weight in liver, muscle, and fibroblasts from Y mice and no detectable SCAD antigen in J mice; MCAD antigen was detected in comparable amounts from both Y and J mice. Radiolabeling and immunoprecipitation studies in J mouse fibroblasts revealed no SCAD synthesis, but normal MCAD synthesis. These data argue against the existence of tissue specific SCAD isoforms in the mouse and confirm that this mouse strain is a model for the human organic aciduria resulting from this beta-oxidation defect. PMID- 1635816 TI - Deletion in blood mitochondrial DNA in Kearns-Sayre syndrome. AB - Mitochondrial DNA deletions have been described in the Kearns-Sayre syndrome (KSS) and the Pearson's marrow-pancreas syndrome. In some cases, the same 4,977 bp deletion has been identified in these two very different diseases. Therefore, it is not currently possible to predict the clinical phenotype from the size or location of the deletion. Instead, differential tissue distribution of the deletion has been implicated as one possible determinant of phenotype. In particular, in KSS the deletions have not been detected by Southern blotting in the blood, whereas in Pearson's syndrome they are easily detectable. We describe here an 11-y-old boy with clinically characteristic KSS and a 7.4-kb mitochondrial DNA deletion between nucleotides 7,194 and 14,595. Southern blotting reveals that 75% of the mitochondrial DNA molecules from his peripheral blood have this deletion. This case blurs further the molecular distinction between the KSS and Pearson's marrow-pancreas syndrome, questioning whether tissue distribution is a sufficient explanation for the very different phenotypes of these disorders. PMID- 1635817 TI - Separation of noncutaneous epithelia in a fetus diagnosed in utero with junctional epidermolysis bullosa. AB - This study was undertaken to identify the extent of involvement of cutaneous and noncutaneous epithelia during expression in utero of junctional epidermolysis bullosa. Skin and other organs from a 19-wk estimated gestational age fetus affected with junctional epidermolysis bullosa and from age-matched controls were examined by light and transmission electron microscopy. In the affected fetus, skin samples from different body regions including trunk, leg, arm, and finger all showed some separation at the dermal-epidermal junction in the plane of the lamina lucida. Hemidesmosomes were absent or hypoplastic, whereas anchoring fibrils appeared normal in structure and number. Interfollicular epidermis appeared to have separated easily, whereas some follicles remained anchored in the dermis. Areas of epithelium in the trachea and bronchi had separated, but within the lung parenchyma the epithelium of smaller bronchioles and alveoli remained attached to supporting connective tissue. The transitional epithelium of the urinary bladder showed small areas of separation compared with the gall bladder epithelium, which showed extensive separation. Gall bladder epithelium in several control fetuses also was consistently separated. In the affected fetus as well as in controls, gall bladder had multiple layers of basal lamina, a previously unrecognized structural feature of human fetal gall bladder. Epithelia that remained intact included the linings of the stomach and small and large intestines and endothelium of large and small vessels in all organs. Kidney, spleen, liver, and lymph nodes appeared normal in all aspects. In control samples, neither skin nor most of the noncutaneous epithelia had separated from the underlying connective tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635818 TI - The expression of surface tissue factor apoprotein by blood monocytes in the course of infections in early infancy. AB - The expression of surface tissue factor procoagulant activity and its shedding by blood monocytes can be induced by several stimuli. Few of these defined situations, other than the presence of bacteria and their toxins, are commonly present in the young human infant. In this study, measurements were made of the percentage of monocytes expressing surface tissue factor apoprotein (TFA) in blood taken from babies in the early weeks of life. Mononuclear cells were separated from blood in an environment free of detectable endotoxin. After exposure to a polyclonal rabbit antibody raised to purified brain TFA and subsequent exposure to a fluorescin-labeled murine anti-rabbit IgG, the cell fluorescent activity was analyzed by flow cytometry. The percentage of monocytes showing strong fluorescence was determined. In every instance when systemic bacterial infection was present, more than 60% of the monocytes examined showed fluorescence indicative of the presence of surface TFA. In a single case of fungal Candida septicemia, none of the monocytes was positive. More than 60% of cells were found to be positive in certain instances where infection was highly probable but not proven. Positive cells were found in three cases of isoimmune hemolytic disease of the newborn, as had been anticipated from previous studies, whereas less than 25% of monocytes derived from babies in the absence of discernible infection or isoimmune hemolytic disease expressed surface TFA (p less than 0.001). These findings provide insight into a possible mechanism of coagulation activation in sepsis and may prove to be a useful predictor of the presence of infection or endotoxemia in young infants. PMID- 1635819 TI - Capillary versus arterial plasma catecholamines as markers for sympatho-adrenal activity in infants. AB - In this study, we investigated whether capillary plasma catecholamines can be used as a suitable substitute for arterial catecholamines. Analysis was done radioenzymatically. Catecholamine concentrations were not different in arterial and simultaneously collected "arterialized" (warmed foot) capillary plasma obtained by heel-prick from 18 neonatal intensive care patients as assessed by linear regression analysis (correlation coefficient: 0.966 for noradrenaline; 0.894 for adrenaline; p less than 0.05) and by a Wilcoxon test [noradrenaline: 2.13 (0.61-10.47) versus 2.41 (1.05-10.23); adrenaline: 0.75 (0.16-1.70) versus 0.72 (0.10-1.37) nmol/L, median (range)]. However, "arterialization" of capillary blood is important; when blood was obtained in nine neonates without warming their feet, capillary concentrations of noradrenaline were higher than arterial values (p less than 0.03) and those of adrenaline were not different from arterial values. Catecholamine concentrations in arterialized capillary plasma collected in healthy full-term infants at 1 h [n = 9; noradrenaline: 6.85 (3.09 8.88) nmol/L; adrenaline: 1.34 (0.86-2.85) nmol/L] and 5 d after birth [n = 27; noradrenaline: 1.58 (0.89-3.16) nmol/L; adrenaline: 0.59 (0.25-1.64) nmol/L] reflect the well-known fall (p less than 0.01) in catecholamine levels after delivery. With a highly sensitive analytical technique, catecholamine concentrations can reliably be assessed in minute samples (100-200 microL) of arterialized capillary blood, even when concentrations have dropped to low "resting" basal levels. Moreover, the capillary sampling procedure is simple and safe, can easily be applied to healthy infants, and does not have the practical and ethical limitations of arterial blood sampling. PMID- 1635820 TI - Bone mineralization outcomes in human milk-fed preterm infants. AB - We evaluated bone mineralization by single photon absorptiometry at 2 y in a cohort of preterm infants studied since birth. Infants were fed human milk fortified with Ca [to achieve 80 mg/dL (19.96 mmol/L)] and P [40 mg/dL (12.91 mmol/L)] from wk 2 through 8 after birth. After hospital discharge, infants were divided into two groups (HM and F) determined by the timing of the introduction of cow milk-based formula. Mid-radius bone mineral content (BMC) was assessed in 10 infants who were breast-fed (HM) for a minimum of 2 mo after hospital discharge and 11 who were bottle-fed (F). The mean duration of human milk-feeding differed by design between HM and F groups (31 +/- 15 versus 11 +/- 3 wk, respectively). Although we had observed previously that group F had significantly greater BMC values at 16, 25, and 52 wk compared with values in group HM, we found similarities in BMC values (180 +/- 30 mg/cm) between groups at 2 y. The 2 y cohort comprised healthy infants and the groups had similar birth weights, lengths of gestation, and values for weight (10.8 +/- 1.1 kg), length (82 +/- 2 cm), and bone width (7.8 +/- 1.1 mm). Follow-up outcomes at 2 y in preterm infants fed fortified human milk in hospital suggest that if they continue to receive human milk after hospital discharge, radius BMC will "catch-up" to that of similar infants given formula in the posthospitalization period. PMID- 1635821 TI - Responses of gastrointestinal peptides and motor activity to milk and water feedings in preterm and term infants. AB - Because duodenal motor activity differs between preterm and term infants during fasting, this study evaluated the responses of motor activity and peptide release in response to feeding. In the first study, fasting concentrations of gastrin, gastric inhibitory peptide, neurotensin, and peptide YY (PYY) were determined in 53 preterm and 20 term infants. Plasma concentrations of gastrin and neurotensin were significantly lower in preterm infants than in healthy adults reported previously by our lab (p less than 0.01). Plasma concentration of gastric inhibitory peptide and PYY were higher than in healthy adults (p less than 0.01). Gastrin concentrations in preterm and term infants varied directly with gestational age (p less than 0.005); PYY varied inversely with gestational age (p less than 0.005). In a secondary study, intestinal manometry was recorded and serial peptide concentrations were determined in 43 preterm babies who were given their first enteral feeding intraduodenally with formula or sterile water. Although none of the four peptide plasma concentrations changed in response to feeding with water, plasma concentrations of gastric inhibitory peptide, neurotensin, and PYY significantly increased with formula feedings (p less than 0.05 or less). In addition, plasma gastrin increased significantly in seven infants fed milk compared with eight fed water by orogastric tube (p less than 0.01). In contrast to the peptide response to feeding, motor activity changed in response to feeding with either water or milk; motility indices increased and periods of motor quiescence decreased significantly during feeding as compared with fasting (p less than 0.02). Responses of both motor activity and peptides to feeding were time related.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635822 TI - Effects of pentoxifylline on the cardiovascular manifestations of group B streptococcal sepsis in the piglet. AB - Pentoxifylline (PTXF) is a methylxanthine that modifies leukocyte function and inhibits cytokine release. To evaluate its effects on the cardiovascular manifestations of sepsis secondary to group B streptococci, 14 anesthetized, mechanically ventilated piglets were studied over a 240-min period. Animals were randomly assigned to a treatment group that received a PTXF bolus (20 mg/kg) followed by a continuous infusion of 5 mg/kg/h before and during group B streptococci (1 x 10(8) colony forming units/kg/min) administration and a control group that received saline as a placebo. Comparison of the hemodynamic measurements and arterial blood gases during the first 90 min of PTXF treatment with those of the control group resulted in the following 90 min values: systemic arterial blood pressure was significantly higher in the PTXF group (89 +/- 10 versus 56 +/- 30 mm Hg; p less than 0.005) as was cardiac output (0.18 +/- 0.04 versus 0.10 +/- 0.07 L/kg/min; p less than 0.005). Pulmonary vascular resistance remained lower in the PTXF-treated animals (135 +/- 117 versus 248 +/- 119 mm Hg/L/min/kg; p less than 0.001), and these animals were less acidotic as measured by pH (7.07 +/- 0.2 versus 7.31 +/- 0.1; p less than 0.05) and base deficit (-15 +/- 9 versus -5 +/- 2 mmol/L; p less than 0.05). Median survival time was significantly longer in the PTXF group (210 versus 90 min; p less than 0.002). These data demonstrate that PTXF can ameliorate some of the deleterious hemodynamic manifestations of group B streptococci sepsis and result in improved survival in a young animal model. PMID- 1635823 TI - Dynamic analysis of cardiac R-R intervals in normal infants and in infants who subsequently succumbed to the sudden infant death syndrome. AB - Infants who subsequently succumb to the sudden infant death syndrome (SIDS) have higher heart rates and reduced heart rate variation compared with other infants. We examined dynamic changes in cardiac interbeat intervals to explore these differences in cardiac control. Recordings of electrocardiographic activity and respiratory movement were acquired from 13 SIDS victims before their deaths. Moment-to-moment changes in R-R intervals during quiet sleep, rapid eye movement sleep, and waking were compared with values of 13 matched control infants. For each sleep-waking state, every R-R interval was plotted against the previous interval (Poincare plots), and each change in interbeat interval was plotted against the previous change. Dispersion of interbeat intervals at different heart rates was reduced in SIDS victims, resulting in Poincare plots markedly different from those of controls. The dispersion, sampled at the 10th and 90th percentiles of heart rates, was reduced across all sleep-waking states in SIDS victims. At high heart rates, the difference between groups disappeared after correcting for basal rate; however, the reduced range at low heart rates was independent of basal rate. SIDS victims also showed smaller beat-to-beat changes in heart rate and fewer sustained runs of consistent heart rate changes during waking relative to controls. The differences in cardiac rate dynamics suggest altered autonomic control in infants who succumb to SIDS. We speculate that the autonomic disturbance may lead to cardiac instability or may indicate CNS alterations with the potential to affect other vital functions. PMID- 1635824 TI - The effects of respiratory training with inspiratory flow resistive loads in premature infants. AB - Respiratory training of premature infants was performed to determine whether improved respiratory muscle strength and/or endurance would result. Twenty-two premature infants were randomized into control and training groups for 2 wk, using inspiratory flow-resistive loads for training (75 cm H2O.L-1.s in wk 1 and 90 cm H2O.L-1.s in wk 2). Respiratory endurance was assessed by the time interval required for the development of a 5-torr rise in transcutaneous CO2 tension during the hypoventilation induced by loaded breathing, using a moderately severe resistive load (250 cm H2O.L-1.s at 1 L.min-1). Respiratory strength was assessed by the maximum negative airway pressure generated during occluded breaths, a pressure-time integral, and an effort index. Results revealed that respiratory muscle endurance, which was not initially different between control and trained groups, increased significantly after 2 wk in the trained group by 137% (median value, p less than 0.05), whereas it remained unchanged in the control group ( 24%). The trained group of infants also showed a significant decrease in baseline breathing frequency between the initial and final measurements taken 2 wk apart when compared with controls (p less than 0.05) and a lesser increase in inspiratory time with loading in the final measurement as compared with the initial value (p less than 0.05). There was no significant difference between the control and trained groups in initial or subsequent measures of respiratory muscle strength. Inspiratory flow-resistive load training appears to improve the respiratory endurance of premature infants in whom respiratory muscle fatigue has been described to play a role in the development of respiratory failure. PMID- 1635825 TI - The relationship between rhythmic swallowing and breathing during suckle feeding in term neonates. AB - Little is known of the development of efficient coordination between suckle feeding and breathing in human infants. To establish baseline data, we recorded breathing and swallowing activity during bottle feeds in 23 infants at 14-48 h postnatal age. Most swallows (overall mean 68%) were organized into runs, with intervals starting at 0.6-0.8 s and slowing to 1-1.3 s after 30-40 s. The proportion of run swallows to total swallows increased significantly with age. Swallow intervals were regular (coefficient of variation = 18-38%) compared with breathing (coefficient of variation = 50%). Both breathing rate and tidal volume were significantly reduced by the onset of suckle feeding, and the pattern of respiratory airflow became markedly irregular. Mild transient desaturation was common, but was not accompanied by changes in heart rate. Swallows could occur in all phases of breathing. Overall, equal numbers of swallows were preceded by expiration and inspiration, but twice as many were followed by expiration compared with inspiration. Swallows were classified by the respiratory phases both preceding and following the swallow. Swallows occurred in all possible classifications in each of the infants studied. The incidence of the most frequent classification (inspiration-swallow-expiration), was 24% overall (individual range 5-50%). The phase relation between swallows and breaths changed frequently but showed occasional short periods of stability during which the breathing became regular and tidal volume increased. We conclude that at less than 48 h the normal infant has little coordination between swallowing and breathing rhythms and maintains rhythmic swallowing at the expense of eupnea. PMID- 1635826 TI - Surfactant lavage in a piglet model of meconium aspiration syndrome. AB - Meconium aspiration continues to be a major cause of morbidity and mortality in newborn infants and is one of the most common indications for extracorporeal membrane oxygenation. Lab studies have suggested that meconium inactivates surfactant and displaces surfactant from the alveolar surface. A recent report has suggested a clinical role for surfactant therapy in human infants with meconium aspiration. We evaluated the effect of surfactant (Survanta) lavage on a piglet model of meconium aspiration. Meconium pneumonitis was created by administration of 4 mL/kg of a 20% slurry of human meconium via endotracheal tube. Twenty-four newborn piglets were then randomly assigned to one of three groups: 1) suction only (n = 7), 2) saline lavage (n = 5), or 3) surfactant lavage (n = 7). Five piglets were excluded from analysis due to death from pneumothorax during meconium administration (n = 3), death from pneumothorax during saline lavage (n = 1), and death from pneumothorax during surfactant lavage (n = 1). The surfactant group had a statistically significant (p less than 0.05) improvement in arterial to alveolar oxygen ratio gradient versus both control groups for the first 3 h. The oxygenation index was statistically significant versus the suction only group at 1, 3, and 4 h. Surfactant lavage of meconium aspiration in piglets results in short-term improvement of oxygenation and warrants further study. PMID- 1635827 TI - Effects of maternal protein-calorie malnutrition on the phospholipid composition of surfactant isolated from fetal and neonatal rat lungs. Compensation by inositol and lipid supplementation. AB - The effects of a maternal protein-calorie malnutrition during gestation and lactation were analyzed on fetal and postnatal lung growth and maturation, including a surfactant fraction isolated from lung tissue. There was a considerable reduction in body weight and in wet and dry lung weights of malnourished pups. Lung protein and DNA concentrations were similar in both groups except in late gestation (lung hyperplasia) and 2 and 15 d after delivery (hypocellularity). Lung glycogen breakdown was slowed down in malnourished newborns. Surfactant material was decreased the most perinatally and the reduction was more marked than for the nonsurfactant fraction of the lung. Disaturated phosphatidylcholine, the major surface active surfactant component, was decreased the most at birth (1.70 +/- 0.31 nmol/mg wet wt versus 3.68 +/- 0.17 nmol/mg in controls, n = 8) and on d 2 (5.04 +/- 0.53 nmol/mg versus 7.67 +/ 0.44 nmol/mg in controls, n = 8). There was an apparent recovery in the composition of surfactant in malnourished rats 5 d after delivery, due in fact to a decrease in controls, and an actual return to normal levels 15 to 20 d after birth. Postnatal lipid supplementation with Intralipid led to partial recovery on d 10. Inositol supplementation totally reverted the effects of malnutrition on surfactant phospholipids (8.36 +/- 0.94 nmol disaturated phosphatidylcholine/mg wet wt on d 2 versus 7.67 +/- 0.44 nmol/mg in controls and 5.55 +/- 0.62 nmol/mg in untreated malnourished rats, n = 10; 2.43 +/- 0.32 nmol disaturated phosphatidylcholine/mg wet wt on d 10 versus 3.26 +/- 0.32 nmol/mg in controls and 1.18 +/- 0.27 nmol/mg in untreated malnourished rats, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635828 TI - Effects of pancuronium bromide on cerebral blood flow changes during seizures in newborn pigs. AB - We investigated the effects of pancuronium bromide pretreatment on cerebral blood flow (CBF) during bicuculline-induced seizures in anesthetized piglets. Arterial blood pressure, gases, pH, cerebral electrocortical activity, and CBF (radioactive microsphere) were monitored at baseline, 10 min after administration of pancuronium (0.3 mg/kg i.v.; n = 9) or vehicle (normal saline; n = 8), and again at 5, 15, and 60 min after bicuculline (3 mg/kg i.v.). No change in CBF from baseline was observed at 10 min after either saline or pancuronium treatment, before induction of seizures. In the saline group, CBF was 36 +/- 3 mL.min-1.100 g-1 before bicuculline and increased to 166 +/- 24 and 205 +/- 35 mL.min-1.100 g-1 at 5 and 15 min, respectively, after bicuculline, returning toward baseline by 60 min. In the pancuronium group at 5 min after bicuculline, CBF increased from 45 +/- 7 to 169 +/- 26 mL.min-1.100 g-1, but fell to 88 +/- 17 mL.min-1.100 g-1 at 15 min in contrast to saline-treated piglets. Also, at 15 min of seizures, differences between groups were observed in arterial blood pressure, gases, and pH. Although these variables were in the normal range with pancuronium treatment, the saline-treated animals had increased arterial blood pressure (81 +/- 6 mm Hg) and PCO2 (6 +/- 0.4 kPa) and decreased PO2 (7 +/- 0.5 kPa) and pH (6.91 +/- 0.06). Electrocortical activity was abnormal during seizures in both groups. At 60 min, reversal to normal activity was observed in six of nine pancuronium-treated animals versus two of eight saline-treated animals. These data suggest that pancuronium limits cerebral hyperemia during prolonged seizures by attenuating increases in blood pressure as a result of elimination of skeletal muscle activity. This leads to minimal alteration of arterial PCO2, PO2, and pH during seizures. PMID- 1635829 TI - Oxygen free radicals and the cerebral arteriolar response to group B streptococci. AB - We used a cranial window preparation to observe the effects of direct application of group B streptococci to the surface of the brain in the adult rat. Continuous exposure to group B streptococci at concentrations of 10(3) and 10(5) organisms/mL caused progressive dilation of surface (pial) cerebral arterioles that became statistically significant (p less than 0.05) after 2.5 h. These results were reproduced with heat-killed organisms at the same concentration, but not with a bacteria-free filtrate of the growth medium. In separate studies, we found that infusion of alkaline cerebrospinal fluid (pH = 7.8) into the window did not reverse vasodilation, suggesting that it was not due to progressive cerebrospinal fluid acidosis. A solution of nitroblue tetrazolium infused into the window at the end of a 3-h exposure to the organism was promptly reduced, suggesting the presence of oxygen free radicals. Treatment with i.v. polyethylene glycol-superoxide dismutase and polyethylene glycol-catalase in doses of 10,000 and 20,000 U/kg, respectively, was itself without effect on pial arterioles, but treatment with these compounds before exposure to group B streptococci eliminated the vasodilation. These data support a role for oxygen free radicals in the pathogenesis of pial arteriolar dysfunction induced by exposure to group B streptococci. PMID- 1635830 TI - Cerebral responses to acute maternal alcohol intoxication in immature fetal sheep. AB - Previous studies in mature fetal sheep have shown that alcohol depresses cerebral blood flow (CBF), cerebral O2 consumption (CMRO2), and cerebral glucose consumption (CMRglu). This effect earlier in gestation might contribute to the pathogenesis of fetal alcohol syndrome. Physiologic studies of immature fetal sheep have demonstrated lower CBF, CMRO2, and CMRglu as well as a blunted vasodilatory response to hypoxia compared with mature fetal sheep. The purpose of this study was to determine whether immature fetal responses to alcohol are blunted compared with near-term fetal responses. We studied seven immature fetal sheep in utero at 92 +/- 1 d gestation (term = 147 d) 2 d after placement of vascular catheters. Pure ethanol (1 g/kg) was infused i.v. to the mother over 1 h. We measured CBF and myocardial blood flow by radioactive microspheres and calculated CMRO2 and CMRglu using arterial and sagittal sinus O2 and glucose concentrations. At a fetal ethanol concentration of 33 + 8 mmol/L (150 +/- 37 mg/dL), there were no significant changes in CBF, CMRO2, or CMRglu. There was mild hypoglycemia (glucose concentration = 1.05 +/- 0.2 versus 1.33 +/- 0.2 mM baseline) and lactic acidemia (lactate concentration = 1.29 +/- 0.3 versus 1.07 +/- 0.2 mM baseline). Cardiovascular variables were unchanged as was myocardial blood flow. The immature fetal sheep brain shows no significant cerebrovascular and metabolic response to acute alcohol intoxication compared with mature fetal sheep. Mild hypoglycemia and lactic acidemia did develop. The reason for the developmental differences in response to alcohol and their relationship to fetal alcohol syndrome remain to be elucidated. PMID- 1635831 TI - Perinatal assessment of cerebral flow velocity wave forms in the human fetus and neonate. AB - The temporal relationship between changes in cerebral Doppler flow velocity wave forms, ductal patency, blood gases, and blood pressure during the transition from intrauterine to newborn life was assessed longitudinally in 16 healthy term fetuses and newborns. Doppler flow velocity wave forms were obtained from fetal cerebral arteries (anterior cerebral, internal carotid, and basilar) before birth, within 8 h after birth, and again at 24 and 48 h after birth. The resistance index was used as a measure of vascular resistance. The resistance index of the cerebral arteries studied increased significantly between the antenatal and 8-h study periods. This was followed by a significant decrease below fetal levels by the 24-h study period, with little change thereafter. We conclude that in the newborn human, as in the newborn lamb, the transition from fetal to immediate newborn life is associated with an increase in cerebral vascular resistance and thus a decrease in cerebral blood flow in response to the increase in arterial oxygenation. The subsequent decrease in the cerebral resistance index between 8 and 24 h of life cannot be explained by a loss of ductal shunting nor by associated changes in newborn blood gases or blood pressure, but may rather reflect a remodeling of the circulation due to impedance matching. PMID- 1635832 TI - Five-year plan for nutrition research and training: executive summary. National Institute of Child Health and Human Development. PMID- 1635833 TI - Pediatric cardiology research in 1990: a review of abstracts submitted to the Society for Pediatric Research, American Academy of Pediatrics, and American Heart Association Scientific Sessions. AB - We assessed pediatric cardiology research by reviewing pediatric cardiology abstracts submitted in 1990 to the Society of Pediatric Research, American Academy of Pediatrics, and American Heart Association national meetings. Included were accepted and rejected studies. Abstracts were reviewed for disease being studied, methodology used to answer the research question, study design, and acceptance/rejection. Abstracts were analyzed from 123 institutions, 81 American and 42 foreign. Out of 423 abstracts, 307 (72.6%) were clinical and the remainder were basic science investigations. Slightly more than half of the clinical submissions were related to congenital heart disease. Coronary artery disease and inflammatory diseases accounted for 12% of clinical submissions. Echocardiography, clinical outcome measures, and electrophysiology were the most common research methodologies. Almost 80% of basic science research was performed in normal tissues; animal physiology, fetal physiology, and cellular/biochemical studies were the most common methodologies. With regard to study design, half of the clinical studies were retrospective and only 6% were either prospective epidemiologic or prospective controlled intervention trials. For basic sciences, 38% of abstracts were descriptions of phenomena and 62% were hypothesis testing, with developmental hypotheses being most common. Acceptance rates favored higher quality study design. However, areas of greatest interest to cardiologists, congenital heart disease, cardiomyopathy, and electrophysiology, had poorer quality study design than did other areas. We have shown broad interest in pediatric cardiology research. However, clinical studies frequently were retrospective or had uncontrolled study designs. Basic science research was performed at a small number of institutions and emphasized either description of phenomena or developmental biology of normal tissues. PMID- 1635834 TI - Brain vasoactive effects of phenobarbital during hypertension and hypoxia in newborn pigs. AB - Phenobarbital in anticonvulsant concentrations has been shown to lower cerebral blood flow (CBF) during hypertension and to reduce the incidence of intraventricular hemorrhage in newborn beagles after hypertensive insult. We proposed that hypoxic dilatation of brain blood vessels might alter the effect of phenobarbital (PBS) on blood flow during hypertension. Thus, in 14 control and nine PBS-treated 1- to 2-d-old newborn piglets, the radio-active microsphere technique was used to determine CBF during 1) steady state (SS), 2) hypertension (HT), and 3) HT plus hypoxia of 5 min duration. In seven controls and in four PBS treated piglets, CBF was also determined during recovery from hypoxia. PBS was infused after SS in a 20-mg/kg dose, and serum levels were obtained 30 min later. Blood pressures were not significantly different between groups when compared during SS, HT, hypoxia, and recovery. Similarly, pH, PO2, and PCO2 were not significantly different between groups when compared during normoxia and hypoxia, and hematocrits were maintained by transfusions after reference sample withdrawals. CBF in control animals increased significantly during HT and remained significantly higher than SS values throughout the 5 min of hypoxia and into the recovery period. In PBS-treated piglets, however, there was no significant increase in CBF during HT. Blood flows also stayed at SS levels during HT plus 5 min hypoxia and recovery from hypoxia. Thus, in newborn piglets, PBS lowered CBF during HT. Furthermore, this blood flow lowering effect persisted during hypoxia, preventing compensatory increases in CBF that might have otherwise occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635835 TI - Hypoxemia and reoxygenation with 21% or 100% oxygen in newborn pigs: changes in blood pressure, base deficit, and hypoxanthine and brain morphology. AB - To study whether room air is as effective as 100% O2 in resuscitation after hypoxia, hypoxemia (PaO2 2.3-4.3 kPa) was induced in newborn pigs (2-5 d old) by ventilation with 8% O2 in nitrogen. When systolic blood pressure had fallen to 20 mm Hg, animals were randomly reoxygenated with either 21% O2 (group 1, n = 9) or 100% O2 (group 2, n = 11) for 20 min followed by 21% O2 in both groups. Controls (group 3, n = 5) were ventilated with 21% O2 throughout the experiment. Base deficit peaked at 31 +/- 5 mmol/L (mean +/- SD) for both hypoxic groups at 5 min of reoxygenation and then normalized over the following 3 h. There were no statistically significant differences between the two groups during reoxygenation concerning blood pressure, heart rate, base deficit, or plasma hypoxanthine. Hypoxanthine peaked at 165 +/- 40 and 143 +/- 42 mumol/L in group 1 and 2 (NS), respectively, and was eliminated monoexponentially in both groups with an initial half-life for excess hypoxanthine of 48 +/- 21 and 51 +/- 27 min (NS), respectively. Blinded pathologic examination of cerebral cortex, cerebellum, and hippocampus after 4 d showed no statistically significant differences with regard to brain damage. We conclude that 21% O2 is as effective as 100% O2 for normalizing blood pressure, heart rate, base deficit, and plasma hypoxanthine after severe neonatal hypoxemia in piglets and that the extent of the hypoxic brain damage is similar in the two groups. PMID- 1635836 TI - Alterations in cerebrovascular reactivity after positive pressure ventilation. AB - Pressure ventilation of the newborn can adversely affect the cardiovascular system. Increasing airway pressure increases cerebral venous pressure, thus stressing brain vasculature. To test the hypothesis that cerebral venous distension caused by mechanical ventilation alters cerebral microvascular responses, we studied cerebrovascular responses before, during, and after positive pressure ventilation. Anesthetized newborn pigs were ventilated with a standard time-cycled, pressure-limited infant respirator. Pial arterioles were measured in response to hypercapnia, topical isoproterenol, and topical norepinephrine during control [mean airway pressure (Paw) = 0.9 +/- 0.05 kPa (4.8 +/- 0.3 cm H2O)] conditions, during 40-60 min of increased Paw [2.5 +/- 0.2 kPa (13.9 +/- 1.3 cm H2O)], and when the Paw was lowered again. Pial arteriolar dilation in response to hypercapnia was not changed by increasing Paw. Similarly, responses to isoproterenol and norepinephrine were unaltered during raised Paw. However, a significant decrease in responses to topical isoproterenol and norepinephrine was observed after increased Paw. These experiments show that specific prostanoid-independent cerebrovascular responses are altered subsequent to pressure ventilation, whereas prostanoid-dependent dilation to hypercapnia was not affected. These changes suggest that the newborn cerebral vasculature is affected by positive pressure ventilation, further raising the possibility that ventilation-induced alterations in microvascular responses could make the brain more vulnerable to added stresses after pressure ventilation. PMID- 1635837 TI - Taurine and osmoregulation. IV. Cerebral taurine transport is increased in rats with hypernatremic dehydration. AB - Taurine is an organic osmolyte in brain cells. We studied whether cerebral taurine transport is enhanced as part of the cell volume regulatory adaptation to hypernatremia. Hypernatremic dehydration was induced for 48 h. Synaptosomes, metabolically active nerve terminal vesicles, were isolated by homogenization of brain and purification on a discontinuous Ficoll gradient. Taurine transport was evaluated in vitro using a rapid filtration assay. After 48 h of hypernatremia, there was a 22.4% increment in Na(+)-specific taurine transport from 2.99 +/- 0.16 to 3.66 +/- 0.13 mumol/mg protein/30 min (p less than 0.001). Dehydration for 48 h without hypertonic saline loading had no effect on taurine uptake. Glycine transport was unaltered by hypernatremia. The adaptation in taurine uptake resulted from an enhanced Vmax of the high affinity-low capacity transport system [265 +/- 17, control versus 337 +/- 19 nmol/min/mg protein, experimental (p less than 0.03)] without a change in the Km (approximately 60 microM). Under both control and hypernatremic conditions, Na+ and Cl- were required for maximal total Na(+)-mediated taurine uptake. Oubain (1 mM) decreased taurine uptake by 25%, whereas addition of beta-alanine or hypotaurine (500 microM) to the external media reduced taurine transport by 45-65% in both control and experimental conditions (p less than 0.01). Synaptosomal taurine uptake in hypernatremic rats was inhibited by 15-20% (p less than 0.01) after addition of 4-acetamido-4' isothiocyanostilbene-2,2'-disulfonic acid (0.1 mM) or 4,4'-diisothiocyanostilbene 2,2'-disulfonic acid (0.1 mM) or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (0.1 mM) to the external medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635838 TI - The frequency of revertants in mdx mouse genetic models for Duchenne muscular dystrophy. AB - The mdx mouse has been used for the development of cellular and gene therapies for Duchenne muscular dystrophy. The relatively frequent occurrence of dystrophin positive muscle cells called revertants has hampered these efforts by interfering with data interpretation. The mdx4cv and mdx5cv dystrophin mouse mutants have approximately 10-fold fewer revertants than the mdx mutant at both 2 and 6 mo. The mdx3cv dystrophin mouse mutant may be a useful model for some types of human dystrophin deficiencies in which the levels of dystrophin are low but not completely absent. PMID- 1635839 TI - Vaccine-induced human antibody responses to the Haemophilus influenzae b polysaccharide in severe combined immunodeficient mice engrafted with human leukocytes. AB - We examined the ability of severe combined immunodeficient (SCID) mice-human peripheral blood leukocyte (PBL) chimeras to respond to immunization with Haemophilus influenzae b polysaccharide (Hib PS) vaccines. Two to 3 wk after PBL engraftment, human-PBL-SCID mice, prepared with PBL from one of five adult donors, were immunized with free or protein-conjugated Hib PS. Antibody to Hib PS was quantitated in preimmunization and postimmunization sera. Before immunization, anti-Hib PS antibody was detectable (greater than 10 ng/mL) in three of 40 mice. Of the 37 human-PBL-SCID mice not having detectable serum antibody before immunization, 31 produced greater than or equal to 20 ng/mL (greater than or equal to 2-fold increase) anti-Hib PS antibody 2 to 3 wk after immunization. Both free and protein-conjugated forms of Hib PS were immunogenic. Geometric mean anti-Hib PS antibody levels ranged from 50 to 139 ng/mL. Vaccine induced anti-Hib PS antibodies frequently expressed HibId-1, a cross-reactive idiotype that predominates the in vivo human antibody response to Hib PS. However, among mice engrafted with PBL from a single donor, the HibId-1 distribution was highly skewed, suggesting that clonally distinct B cells were being stimulated in individual mice. These findings indicate that human PBL transplanted into SCID mice are functionally responsive to Hib PS antigenic challenge. This system may serve as a useful model for studying the regulation and cellular requirements for human polysaccharide immunity. PMID- 1635840 TI - Mitochondrial myopathy studies on permeabilized muscle fibers. AB - Respiratory parameters of skeletal muscle were determined in permeabilized muscle fibers by adapting a technique described by Veksler et al. for cardiac fibers (Biochim Biophys Acta, 892:191-196, 1987). This method consists of the permeabilization of muscle fibers by saponin by allowing respiratory substrates and inhibitors to reach the mitochondria. In this way, the mitochondria may be studied inside the fibers as if they were isolated. We have verified, using various techniques, that the mitochondria remain intact during this procedure. This method has been applied to the study of six newborn infants for whom a diagnosis of a mitochondrial defect was suspected. In all cases, the defect was to be found on the permeabilized fibers, and this was confirmed by an enzymatic study. The advantage of this new method, associated with the measurement of the enzymatic activities on a crude homogenate, is to enable a simple and rapid diagnosis on a small amount of sample without damaging the mitochondria during the isolation procedure. PMID- 1635841 TI - Cardiac teratogenicity of dichloroethylene in a chick model. AB - Trichloroethylene (TCE) and dichloroethylene (DCE) are related halogenated aliphatic hydrocarbon industrial solvents that are frequently found as drinking water contaminants. TCE has been implicated as a cardiac teratogen in an epidemiologic study and in a chick model. The purpose of this study was to determine whether DCE was also a cardiac teratogen in the chick embryo. Fertilized White Leghorn chick eggs (n = 418) were inoculated just above the embryo with 30 microL of a test solution on d 3 of incubation. Two control groups were studied: normal saline (n = 96) and the diluent for the DCE, mineral oil (n = 108). DCE was studied at three doses: 5, 20, and 25 microM (n = 76, 62, and 76, respectively). Eggs were coded with a seven-digit number to mask identity. Chicks were terminated on d 18 of incubation, and, after external inspection, hearts and great vessels were dissected macroscopically according to a detailed protocol. Abnormal hearts were reviewed and the diagnosis was agreed upon by three investigators before decoding the seven-digit number and photographing the abnormality. Some embryo death and subsequent tissue autolysis occurred in all groups, but, compared to controls, it was not significantly greater in the treatment group. However, combining all controls and all experimentals, significantly more (p = 0.02) embryonic death occurred in the experimental group. Noncardiac anomalies occurred in 17 embryos and were highest in the saline (four), 5 microM (four), and 20 microM (seven) DCE groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635842 TI - Myocardial carbohydrate, ketone, and fatty acid uptake in conscious lambs with aortopulmonary shunts. AB - A left to right shunt increases myocardial work and is often accompanied by increased catecholamine levels. Because both increased myocardial work and increased catecholamine levels may induce increased fatty acid utilization, which could increase resting myocardial oxygen consumption and therefore unfavorably affect coronary reserve, we studied myocardial uptake of glucose, pyruvate, lactate, beta-OH-butyrate, acetoacetate, FFA, and triglycerides in 12 7-wk-old lambs with aortopulmonary left to right shunts (58 +/- 2% of left ventricular output, mean +/- SEM) and in 10 control lambs 2 wk after surgery. Despite the shunt, systemic blood flow in the shunt lambs was maintained at the same level as in the control lambs. This was accomplished by an increased heart rate and stroke volume. Furthermore, the shunt was accompanied by an increased myocardial oxygen consumption in the shunt lambs (834 +/- 70 versus 528 +/- 43 mumol O2.min-1 x 100 g-1; p less than 0.05). There were no significant differences in arterial substrate concentrations between the two groups. The same was true for arteriovenous differences across the myocardium, with the exception of lactate, which was substantially higher in shunt than in control lambs (72 +/- 25 versus 18 +/- 23 mumol/L; p less than 0.05). As a consequence, myocardial lactate uptake in the shunt lambs was increased 15-fold (18 +/- 6 versus 1 +/- 2 mumol.min-1 x 100 g-1; p less than 0.02), whereas uptake of the other substrates merely paralleled the increased myocardial blood flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635843 TI - A study of galactose intolerance in human and rat liver in vivo by 31P magnetic resonance spectroscopy. AB - An oral load of 20 mg/kg galactose produces significant changes in the 31P magnetic resonance spectrum of the liver of a galactosemic patient. The peak at 5.2 ppm (which includes inorganic phosphate and galactose-1-phosphate) increased on two occasions to about twice its original size 60 min after galactose administration. An oral load of 10 mg/kg galactose given to a second patient produced no discernible changes at 30 min. We have also used an animal model of galactose intolerance, in which galactose metabolism in rats was blocked by the acute administration of ethanol. Studies in vivo and in vitro showed that the increase in the peak at 5.2 ppm was largely due to galactose-1-phosphate. We have shown in this preliminary study that small amounts of galactose can produce significant elevation of hepatic galactose-1-phosphate, which can be detected by 31P magnetic resonance spectroscopy. PMID- 1635844 TI - Starch digestion in young children with cystic fibrosis measured using a 13C breath test. AB - The study was designed to evaluate a non-invasive breath test using naturally 13C rich corn (maize) as substrate to provide quantitative information about the digestion of starch by children in health and disease. The variability of background 13C:12C of young British children was investigated by collecting breath samples over 6 h from 17 healthy children, 6-35 mo old, and from seven children with cystic fibrosis, 25-48 mo old, in their homes. Background 13C enrichment was -26.6 and -25.4 delta per mil in the healthy and cystic fibrosis groups, respectively (p less than 0.01), and varied little during the day (SD = 0.4 delta per mil). Eight healthy children and five with cystic fibrosis were given a test breakfast of corn starch cooked in milk with sugar. The cystic fibrosis group repeated the test with the addition of an enzyme supplement containing alpha-amylase. Subjects accepted variable amounts of starch (range 0.2 2.8 g/kg body wt). The percentage of ingested 13C recovered during the 6 h after the meal increased with age in the healthy children (range 15-53%). Three children with cystic fibrosis had negligible 13C recoveries, and the other two had lower recoveries than expected for their age. The addition of enzymes did not consistently improve 13C recovery. We conclude that the 13C breath test based on corn has potential for investigating starch digestion in young children. Initial results suggest that starch digestion is impaired in some children with cystic fibrosis and that enzyme supplements do not improve digestion consistently or completely. PMID- 1635845 TI - Development of the neonatal rat small intestinal barrier to nonspecific macromolecular absorption. II. Role of dietary corticosterone. AB - The role of oral corticosterone (C) in the maturation of the neonatal rat jejunal barrier to the absorption of nonspecific macromolecules was evaluated. This was done by adding C to the diet of rat pups weaned at an early age, 17 d, from maternal milk (MM) to either a protein hydrolysate (PH) or soy (S) artificial formula. Both PH and S are known to cause a delay in small intestinal closure to the absorption of a 40-kD glycoprotein tracer, horseradish peroxidase (HRP), on d 21 of age. C was added to PH and S formulas from d 17 to 21 at 0.26 mumol/L (10 micrograms/dL), a level found in the MM of lactating rat dams, or at 10.29 mumol/L (400 micrograms/dL) (PH + 10C, PH + 400C) (S + 10C, S + 400C). Controls consisted of rat pups fed PH or S without C and animals remaining with the dam on MM. The delay in jejunal closure to HRP on d 21 in both PH- and S-fed pups was prevented by C supplementation at both the higher and lower concentrations. Geometric mean (95% confidence intervals) jejunal HRP absorption in PH + 10C pups was 74 (32,167) IU HRP/mL x cm x min, less than in pups fed PH without C [353 (200,615); p less than 0.05] and indistinguishable from HRP absorption in MM-fed animals [111 (79,154)]. HRP absorption in PH + 400C pups [52 (23,115)] was also less than that in animals fed PH without C (p less than 0.01) and indistinguishable from those fed MM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635846 TI - Polyamine concentration in rat milk and food, human milk, and infant formulas. AB - The polyamine concentration in rat milk and food, human milk, and infant formulas was estimated by HPLC. In rat milk, the concentration of putrescine and spermine was low (generally under 2.5 nmol.mL-1 for putrescine and under 1 nmol.mL-1 for spermine). The spermidine concentration was higher and seemed to increase during lactation. The rat food was richer in polyamines than the rat milk (about 150 times for putrescine and spermine, about 30 times for spermidine). We already proved that ingestion of spermine or spermidine can induce precocious maturation of the rat intestine. The present observations suggest that polyamines contained in rat food could play an important role in postnatal maturation of the rat intestine. The polyamine concentration of human milk was measured from 60 different mothers during a period extending from the 1st wk to the 6th mo of lactation. Great variation was observed. During the 1st mo of lactation, the general pattern was as follows: putrescine concentration generally varied little (from 1 to 3 nmol.mL-1), spermine and spermidine concentrations showed a similar pattern (the highest values appeared at the end of the 1st wk of suckling). After the 4th mo of lactation, putrescine concentration increased slightly, whereas spermine and spermidine concentration stayed almost stable. The concentrations of polyamines in 18 powdered milks for babies were estimated. Spermine and spermidine contents were lower than those in human milk. A protective effect of spermine or spermidine against alimentary allergies is suggested. PMID- 1635847 TI - Serum growth hormone-binding proteins in the human fetus and infant. AB - Growth hormone-binding protein (GH-BP) levels were studied in cord serum of 69 human infants born after 24 to 41 wk of gestation and in serum of 14 infants aged 1 to 3 mo. GH-BP levels were measured by HPLC-gel filtration of serum incubated overnight with 125I-hGH. The radioactive elution profile revealed two small 125I hGH peaks of high molecular weight and a large peak, corresponding to monomeric 125I-hGH. The first peak of high molecular weight was variable, showed some of the characteristics (high molecular weight, displaceability by a large excess of unlabeled hGH) of the described low affinity, high capacity GH-BP, and did not correlate with gestational age or birth weight (peak I-BP). The second peak was identified as 125I-hGH bound to the high affinity, low capacity GH-BP (peak II BP). Mean +/- SD specific binding of 125I-hGH to this peak was significantly (p less than 0.0001) different between preterm infants (3.1 +/- 1.1%; n = 51), term infants at birth (4.2 +/ 1.1%; n = 18), and 1- to 3-mo-old infants (8.5 +/- 1.6%; n = 14). To evaluate the effect of intrauterine nutritional state, the ponderal index (weight/lengths) was calculated. Peak II-BP levels were lower (p less than 0.05) in infants with the ponderal index less than 2.35 (2.8 +/- 1.0%; n = 20) than in those with the ponderal index between 2.35 and 2.65 (3.4 +/- 1.2%; n = 29) or greater than 2.65 (3.8 +/- 1.2%; n = 20).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635848 TI - Clinical usefulness of urinary growth hormone measurements in normal and short children according to different expressions of urinary growth hormone data. AB - To assess the clinical usefulness of urinary growth hormone (UGH) measurements, a UGH determination technique, including dialysis, ultrafiltration, and measurement by polyclonal-coated tube RIA, was established. Sixty-three short children were studied: 56 idiopathic growth retarded (37 prepubertal and 19 pubertal) and seven prepubertal with classic GH (growth hormone) deficiency. Forty-two healthy children (32 prepubertal and 10 pubertal) served as controls. Two groups of adults were studied: eight with active acromegaly and 11 healthy controls. UGH was measured in 24-h urine samples from all patients and controls. Mean +/- SD UGH excretion expressed as ng/24 h was significantly lower in the GH-deficient group compared with prepubertal growth-retarded and control children (p less than 0.01). No differences were found between UGH excreted by controls and by the growth-retarded groups. Pubertal children excreted significantly higher amounts of GH when UGH was expressed as ng/24 h (p less than 0.02 and p less than 0.03, respectively), but this difference disappeared when UGH was expressed as ng/g creatinine. UGH was significantly higher in acromegalic patients compared with adult controls (p less than 0.001). Differences between day, night, and 24-h UGH were studied in 23 children. UGH in night urine was significantly lower whether expressed as the total amount or as ng/g creatinine. The effect of recombinant hGH administration on UGH was studied in 13 children after 6 and 12 mo of treatment. UGH increased significantly under recombinant hGH treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635849 TI - Dual energy x-ray absorptiometry measurement of bone mineral content in newborns: validation of the technique. AB - To evaluate the applicability of dual energy x-ray bone absorptiometry in newborns, precision and accuracy of the method was tested for very small quantities of mineral ranging from less than 0.5 g to about 4 g of hydroxyapatite using a Hologic QDR 1000 instrument. For six femurs excised from preterm stillborns, the mean precision for bone mineral content (BMC) and bone mineral density (BMD) was 1.2 and 0.8%, respectively. Accuracy based on ash weight indicated a mean overestimation of about 7%. In vivo, the precision was assessed by measuring lumbar spine BMC and BMD (L1 to L5) two or three times in 10 newborns (gestational age, 33 to 40 wk). The mean coefficients of variation were 2.40 and 1.55% for BMC and BMD, respectively. Lumbar spine BMC and BMD were also measured once in 30 full-term infants. Values ranged from 1.17 to 3.90 g for BMC and from 0.192 to 0.356 g/cm2 for BMD. The present study shows that dual energy x ray absorptiometry provides a valuable new tool for the assessment and management of BMC in low birth weight infants and neonates in general. PMID- 1635850 TI - Prostaglandin E2 attenuates hyperoxia-induced injury in cultured rabbit tracheal epithelial cells. AB - We assessed the kinetics of hyperoxia-induced prostaglandin E2 (PGE2) production by cultured rabbit tracheal epithelial (TE) cells with different inherent capacities to generate PGE2 and the role of endogenous PGE2 production in protecting these cells from hyperoxic injury. Rabbit TE cells grown to confluence with or without lipid supplements [0.1% Excyte III (Miles-Pentex) and 1 microM arachidonic acid] were exposed for 2 h to control (5% CO2/air) or hyperoxic (5% CO2/90% O2) atmospheres at a gas-fluid interface. Serial cell culture effluents collected during exposure were analyzed for PGE2 by enzyme-linked immunoassay. Basal PGE2 production by lipid-supplemented cells was approximately 3-fold greater than that by unsupplemented cultures (p less than 0.01). In lipid supplemented cells, PGE2 production doubled after 15 min of hyperoxic exposure (p less than 0.05) and then declined to approximately 50% of initial levels, whereas exposure to 5% CO2/air did not significantly change PGE2 production. In unsupplemented cells, neither control nor hyperoxic exposure altered PGE2 production. Hyperoxia-exposed TE cells had decreased ability to convert 10 microM exogenous arachidonic acid to PGE2, suggesting hyperoxia-induced inhibition of the enzymes involved in PGE2 synthesis. Lipid-supplemented cells were less susceptible to hyperoxic injury than unsupplemented monolayers, as evidenced by increased viability (trypan blue exclusion) and decreased generation of lipid peroxides (thiobarbituric acid reactive substances). Addition of exogenous PGE2 to unsupplemented cultures at concentrations that were produced by lipid supplemented cells (2 ng/mL every 15 min) during hyperoxic exposure eliminated these differences in hyperoxia-induced lipid peroxidation and cytotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635851 TI - Mechanical fragility of erythrocyte membrane in neonates and adults. AB - The shortened life span of neonatal red blood cells (RBC) is associated with accelerated membrane loss. The present study was designed to measure the critical shear force that causes membrane failure and the rate of membrane failure for neonatal and adult RBC. A micropipette technique was used to determine the membrane extensional (shear) elastic modulus (i.e. resistance of the membrane to extensional elastic deformation), the rate of extensional membrane deformation (i.e. surface viscosity), and the tension for local membrane fragmentation. A flow channel system was used to determine the critical shear force of plastic membrane deformation (i.e. beginning of membrane tether formation), the rate of plastic deformation, and the plastic shear viscosity coefficient. The extensional elastic modulus of neonatal RBC was 18% smaller and the rate of elastic deformation was 25% longer compared with adult cells (p less than 0.05). Membrane surface viscosity was similar for both cell types. The tension for local membrane fragmentation in the micropipette was 23% lower in neonates than in adults. However, the strain (i.e. extent of membrane deformation calculated as ratio of the stress resultant and the elastic modulus) at which membrane rupture in the micropipette occurred was similar for neonatal and adult RBC. This indicates that the smaller critical tension for neonatal RBC membrane failure was due to increased membrane elastic deformability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635852 TI - Blood viscosity and optimal hematocrit in preterm and full-term neonates in 50- to 500-micrometer tubes. AB - Blood viscosity is an important determinant of blood flow resistance. Because a substantial part of flow resistance arises in small arteries and arterioles with diameters of 100 microns and less, rheologic properties of blood from preterm infants (24 to 36 wk of gestation), full-term neonates, and adults were measured in glass tubes with diameters of 50, 100, and 500 microns for a wide range of adjusted feed hematocrits (0.15-0.70). At each of the feed hematocrits, blood viscosity decreased when going from a 500-microns tube to a 50-microns tube. The viscosity reduction increased with increasing hematocrit. Moreover, the viscosity reduction was more pronounced in the neonates than in the adults. At a hematocrit of 0.70, the viscosity reduction averaged 56% in preterm infants, 50% in full term neonates, and 39% in adults (p less than 0.005). However, the viscosity reductions at a hematocrit of 0.30 were only 35, 29, and 19%, respectively (p less than 0.05). In all four groups, blood viscosity increased exponentially with increasing hematocrit. The steepness of the hematocrit-viscosity curves decreased with decreasing tube diameter and with decreasing maturity of the infants. Erythrocyte transport efficiency (hematocrit/blood viscosity) was calculated to estimate the optimal hematocrit (i.e. hematocrit with maximum erythrocyte transport). In 500-microns tubes, the optimal hematocrit was about 0.40 in all of the groups. In 100-microns tubes, the optimal hematocrit was 0.44 +/- 0.05 in the adults and 0.52 +/- 0.04 in the neonates (p less than 0.05). In 50-microns tubes, the optimal hematocrit was 0.51 +/- 0.04 in adults and 0.60 +/- 0.05 in the neonates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635853 TI - Primacy of dimensions in vibrotactile perception: an evaluation of early holistic models. AB - Early holistic models of perception presume that stimuli composed of interacting dimensions can be experienced initially as undifferentiated. This view, formalized through recourse to a Euclidean geometry of perceptual space, predicts that the orientation of axes used to create stimulus sets is unimportant to performance in speeded classification. We tested this idea by using the interacting vibrotactile dimensions of pitch and loudness. Despite perceivers' relatively poor experience with these dimensions, we showed that the orientation corresponding to pitch and loudness was unique in vibrotactile perceptual space; subjects classified stimuli more efficiently at this orientation than at other orientations. Certain holistic models also claim that when stimulus differences are small, perceivers can recognize change without distinguishing the kind of change. We tested this idea by using a signal detection analysis of unspeeded same-different decisions. We found that subjects' ability to notice the kind of change equaled their ability to notice the change alone. In view of these results, which indicate that pitch and loudness are primary in vibrotactile perception, we detail a new conception of dimensional interaction. PMID- 1635854 TI - In defense of the right and left audiograms: a reply to Coren (1989) and Coren and Hakstian (1990) AB - Coren (1989) noticed that the various air-conduction pure-tone thresholds obtained from one ear of an individual in quiet tend to display a high correlation. In addition, Coren and Hakstian (1990) reported a consistently high correlation between pure-tone thresholds in the two ears of the same individual. On the basis of these observations, these authors proposed that pure-tone thresholds measured at audiometric frequencies in one ear, and those measured in both ears of an individual, be collapsed into a single average threshold value. The present paper disputes the usefulness and the appropriateness of such a proposal. PMID- 1635855 TI - On the perception of shape from shading. AB - The extraction of three-dimensional shape from shading is one of the most perceptually compelling, yet poorly understood, aspects of visual perception. In this paper, we report several new experiments on the manner in which the perception of shape from shading interacts with other visual processes such as perceptual grouping, preattentive search ("pop-out"), and motion perception. Our specific findings are as follows: (1) The extraction of shape from shading information incorporates at least two "assumptions" or constraints--first, that there is a single light source illuminating the whole scene, and second, that the light is shining from "above" in relation to retinal coordinates. (2) Tokens defined by shading can serve as a basis for perceptual grouping and segregation. (3) Reaction time for detecting a single convex shape does not increase with the number of items in the display. This "pop-out" effect must be based on shading rather than on differences in luminance polarity, since neither left-right differences nor step changes in luminance resulted in pop-out. (4) When the subjects were experienced, there were no search asymmetries for convex as opposed to concave tokens, but when the subjects were naive, cavities were much easier to detect than convex shapes. (5) The extraction of shape from shading can also provide an input to motion perception. And finally, (6) the assumption of "overhead illumination" that leads to perceptual grouping depends primarily on retinal rather than on "phenomenal" or gravitational coordinates. Taken collectively, these findings imply that the extraction of shape from shading is an "early" visual process that occurs prior to perceptual grouping, motion perception, and vestibular (as well as "cognitive") correction for head tilt. Hence, there may be neural elements very early in visual processing that are specialized for the extraction of shape from shading. PMID- 1635857 TI - Amplitude discrimination of sinusoids and narrow-band noise with Rayleigh properties. AB - The ability of human observers to discriminate differences in the amplitude of sinusoids and narrow-band noises was measured by the rating method of detection theory. Although each sinusoid (always 1000 Hz) was presented at a fixed amplitude, its amplitude on any trial was drawn from one of two Rayleigh probability distributions that differed in mean amplitude: a signal distribution and a noise distribution. Similarly, the amplitudes of the narrow-band noises were distributed as the Rayleigh distribution by virtue of the reciprocal relation between their bandwidth (100 Hz centered on 1000 Hz) and duration (10 msec). The obtained psychometric functions showing the area under the ROC as a function of signal-to-noise ratio were similar for both kinds of signals and were displaced, on average, about 4 dB from an ideal observer's function. The slopes of the obtained functions were similar to those of an ideal observer using 1 degree of freedom--half the number available in Rayleigh noise. PMID- 1635856 TI - Characterizing the influence of native language experience on adult speech perception. AB - Previous cross-language research has indicated that some speech contrasts present greater perceptual difficulty for adult non-native listeners than others do. It has been hypothesized that phonemic, phonetic, and acoustic factors contribute to this variability. Two experiments were conducted to evaluate systematically the role of phonemic status and phonetic familiarity in the perception of non-native speech contrasts and to test predictions derived from a model proposed by Best, McRoberts, and Sithole (1988). Experiment 1 showed that perception of an unfamiliar phonetic contrast was not less difficult for subjects who had experience with an analogous phonemic distinction in their native language than for subjects without such analogous experience. These results suggest that substantive phonetic experience influences the perception of non-native contrasts, and thus should contribute to a conceptualization of native language processing skills. In Experiment 2, English listeners' perception of two related nonphonemic place contrasts was not consistently different as had been expected on the basis of phonetic familiarity. A clear order effect in the perceptual data suggests that interactions between different perceptual assimilation patterns or acoustic properties of the two contrasts, or interactions involving both of these factors, underlie the perception of the two contrasts in this experiment. It was concluded that both phonetic familiarity and acoustic factors are potentially important to the explanation of variability in perception of nonphonemic contrasts. The explanation of how linguistic experience shapes speech perception will require characterizing the relative contribution of these factors, as well as other factors, including individual differences and variables that influence a listener's orientation to speech stimuli. PMID- 1635858 TI - Visual search for direction of shading is influenced by apparent depth. AB - Recent reports of rapid visual search for some feature conjunctions suggested that preattentive vision might be sensitive to scene-based as well as to image based features (Enns & Rensink, 1990a, 1990b). This study examined visual search for targets defined by the direction of a luminance gradient, a conjunction of luminance and relative location that often corresponds to object curvature and direction of lighting in naturalistic scenes. Experiment 1 showed that such search is influenced by several factors, including the type of gradient, the shape of the contour enclosing the gradient, and the background luminance. These factors were varied systematically in Experiment 2 in a three-dimensionality rating task and in a visual-search task. The factors combined interactively in the rating task, supporting the presence of an emergent property of three dimensionality. In contrast, each factor contributed only additively to the speed of the visual-search task. This is inconsistent with the view that search is guided by specialized detectors for surface curvature or direction of lighting. Rather, it is in keeping with the view that search is governed by a number of "quick and dirty" processes that are implemented rapidly and in parallel across the visual field. PMID- 1635860 TI - Strength of visual interpolation depends on the ratio of physically specified to total edge length. AB - We report four experiments in which the strength of edge interpolation in illusory figure displays was tested. In Experiment 1, we investigated the relative contributions of the lengths of luminance-specified edges and the gaps between them to perceived boundary clarity as measured by using a magnitude estimation procedure. The contributions of these variables were found to be best characterized by a ratio of the length of luminance-specified contour to the length of the entire edge (specified plus interpolated edge). Experiment 2 showed that this ratio predicts boundary clarity for a wide range of ratio values and display sizes. There was no evidence that illusory figure boundaries are clearer in displays with small gaps than they are in displays with larger gaps and equivalent ratios. In Experiment 3, using a more sensitive pairwise comparison paradigm, we again found no such effect. Implications for boundary interpolation in general, including perception of partially occluded objects, are discussed. The dependence of interpolation on the ratio of physically specified edges to total edge length has the desirable ecological consequence that unit formation will not change with variations in viewing distance. PMID- 1635859 TI - Determinants of the perception of sagittal motion. AB - This study examines the change in the perceived distance of an object in three dimensional space when the object and/or the observer's head is moved along the line of sight (sagittal motion) as a function of the perceived absolute (egocentric) distance of the object and the perceived motion of the head. To analyze the processes involved, two situations, labeled A and B, were used in four experiments. In Situation A, the observer was stationary and the perceived motion of the object was measured as the object was moved toward and away from the observer. In Situation B, the same visual information regarding the changing perceived egocentric distance between the observer and object was provided as in Situation A, but part or all of the change in visual egocentric distance was produced by the sagittal motion of the observer's head. A comparison of the perceived motion of the object in the two situations was used to measure the compensation in the perception of the motion of the object as a result of the head motion. Compensation was often clearly incomplete, and errors were often made in the perception of the motion of the stimulus object. A theory is proposed, which identifies the relation between the changes in the perceived egocentric distance of the object and the tandem motion of the object resulting from the perceived motion of the head to be the significant factor in the perception of the sagittal motion of the stimulus object in Situation B. PMID- 1635861 TI - Heartbeat--the rhythm of health. PMID- 1635863 TI - Human lactation and breast feeding management. PMID- 1635864 TI - Acknowledging the forgotten priority. PMID- 1635862 TI - Self directed learning: the development of a learning plan. PMID- 1635865 TI - American Cancer Society announces 1992 Lane W. Adams Award recipients. PMID- 1635866 TI - The challenge of caring in oncology nursing. PMID- 1635867 TI - Music therapy: a gift beyond measure. PMID- 1635868 TI - Families: an essential element in the care of the patient with cancer. PMID- 1635869 TI - The process of maintaining hope in adults undergoing bone marrow transplantation for leukemia. AB - The purpose of this qualitative study was to explore the processes of hoping in adults undergoing bone marrow transplantation (BMT) for leukemia. Grounded theory methodology was used to elicit the experience of hoping in 10 men and 10 women, ages 20-58, who had undergone BMT. The central process described by participants was that of maintaining hope. The core categories used to describe this process were Dealing With It and Keeping It in Its Place. Dealing With It is defined as the process of confronting the negative possibilities inherent in the illness experience and allowing the full range of thoughts, behaviors, and emotions resulting from this confrontation. Keeping It in Its Place is defined as the process of managing the impact of the illness by controlling or limiting one's response to the disease and therapy. The relationship between these two contradictory core categories is explained by The Dialectic of Maintaining Hope. This dialectic is defined as the synthesis of the antithetical strategies of Dealing With It and Keeping It in Its Place in which people are able to transcend each strategy and sustain hope. The findings provide a nascent, explanatory model and information for nurses regarding an important adaptive process. PMID- 1635870 TI - The oncology nurse's role in patient advance directives. AB - In December 1991, Patient Self-Determination Amendment (PSDA) legislation was implemented. The PSDA requires facilities funded by Medicare/Medicaid to inform patients of their decision-making rights regarding medical care. An advance directive (AD), a living will, or a durable power of attorney for health care contains statements made by competent people directing their medical care if they should become incompetent. Oncology nurses are in an advantageous position to educate and advocate for their patients with respect to end-of-life decisions. They are qualified to facilitate the AD process by virtue of their ability to relate to patients and families their extensive experience with the terminally ill and their expertise as liasons between patients, families, and the multidisciplinary team. A clear understanding of the patient's wishes regarding life-sustaining treatments enables the oncology nurse to advocate more effectively on the patient's behalf. This article highlights definitions of ADs, advantages and disadvantages of each, and recommendations for the oncology nurse's practice. PMID- 1635871 TI - Patients who have undergone bone marrow transplantation: their quest for meaning. AB - This study investigates the processes of "meaning-making" and life interpretation as experienced by a group of patients who underwent bone marrow transplantation. Six adult male patients were followed until the 100th day after their transplantation or until their deaths. A hermeneutic study of their experiences revealed that they manipulated the meanings of their lives and sought meaning in their lives in two different ways: (1) they renegotiated their social position in a new situation, and (2) they tried to reach an understanding of their experiences as a whole. PMID- 1635872 TI - Early and late radiation-induced skin alterations. Part II: Nursing care of irradiated skin. AB - Teaching patients how to care for irradiated skin during and after a course of radiation therapy is a major concern of oncology nurses. Part I of this two-part article (ONF 19(5):801-807) focused on the mechanisms of skin injury. Many topical preparations are available for skin care. When these substances are applied, both the active ingredient and the vehicle must be appropriate for the condition being treated. Preparations may be applied to the skin as liquids (e.g., lotions, solutions, tinctures used in wet dressings, soaks, baths) or solids (e.g., powders, creams, ointments). As skin reaction progresses during a course of radiation therapy, recommendations for skin care will change. Healing of injury occurs in three stages: inflammation, proliferation, and maturation. Wound healing proceeds more rapidly in a moist environment, and a variety of occlusive dressings can be used with moist desquamation. PMID- 1635873 TI - Oncology nursing society position paper on cancer and aging: the mandate for oncology nursing. PMID- 1635874 TI - Better education results in less stomatitis. PMID- 1635875 TI - Peridex decreases oral mucositis. PMID- 1635877 TI - Assessment promotes proper oral care. PMID- 1635876 TI - Alternatives to unwaxed floss and peroxide rinses recommended. PMID- 1635878 TI - Ongoing assessment of patient teaching remains important. PMID- 1635879 TI - Oral care of patients receiving radiation therapy to head and neck. PMID- 1635880 TI - Educational guide improves management of xerostomia. PMID- 1635882 TI - Fumes from the spleen. PMID- 1635881 TI - Mantel-Haenszel techniques and logistic regression: always examine one's data first and don't overlook the simpler techniques. AB - The authors point out that, in addition to logistic regression, there are other, simpler techniques available for making an adjusted estimate of association between an outcome and a risk factor. Also, the consequence of mismodelling with regression, i.e. of missing the real relationship between an outcome and a risk factor, is illustrated with an example. The need to 'examine one's data' prior to performing multivariable techniques is emphasised. PMID- 1635883 TI - Risk factors in limb reduction defects. AB - Risk factors were studied in 123 children with limb reduction defects (LRD) from 118,265 consecutive births of known outcome during the period from 1979 to 1987 in the area which is covered by our registry of congenital malformations. For each case a control was studied. The LRD was localised and classified according to the EUROCAT guide for the description and classification of limb defects. The prevalence of LRD was 1.04 per thousand: 82.9% of the babies were liveborn, 13.0% were late spontaneous abortion or stillborn and termination was performed in 4.0% of the cases. The proportion of males was 0.55. The most common malformations in the 51.2% of children who had at least one other anomaly than LRD were associated cardiac, digestive and renal anomalies. The pregnancy with limb anomalies was more often complicated by oligohydramnios, polyhydramnios and threatened abortion but there were no differences in parental characteristics. However, 9.7% of marriages were consanguineous (P less than 0.01) and the incidence of LRD in first-degree relatives of the children with LRD was high. First-degree relatives also had more non-limb malformations than did those of controls. PMID- 1635884 TI - The California Cerebral Palsy Project. AB - The California Cerebral Palsy Project (CACP) is a population-based study of 192 children with moderate or severe congenital cerebral palsy who were born between 1983 and 1985 in four San Francisco Bay area counties and who were alive and residing in California at age 3 years. Initial ascertainment of cases was based on records of two agencies known to enrol virtually all CACP-eligible children. Final case status was established by standardised clinical examination in 67% of cases and extensive record review in 33%. The 192 cases gave a prevalence at age 3 of 1.23/1000 survivors. Twins were 10% of the cases with a prevalence of 6.7/1000. Overall, 53% of the cases had birthweight greater than or equal to 2500 g and 28% had birthweight less than 1500 g. There was no association between birthweight and severity of functional impairment and no consistent association between birthweight and the presence of associated disabilities. The CACP prevalence is lower than that reported in other studies and is believed to be due to the more stringent case inclusion criteria employed for this research data base. PMID- 1635885 TI - Prenatal events and the risk of subependymal/intraventricular haemorrhage in very low birthweight neonates. AB - The effects of prenatal factors on the risk of subependymal and/or intraventricular brain haemorrhage in very low birthweight (VLBW) neonates were studied. Data were collected on 201 consecutively born VLBW neonates without major congenital anomalies, who were born at a regional obstetric referral centre. Brain haemorrhage was identified by cranial ultrasound examinations. The reliability of these examinations (concordance among readers' interpretations) was assessed and found to be moderate (kappa = 0.47 for the finding of subependymal haemorrhage (SEH); kappa = 0.50 for the finding of intraventricular haemorrhage (IVH)). Prenatal factors were more strongly associated with IVH than with SEH. In univariable analyses, maternal pre-eclampsia, multiple gestation and maternal treatment with betamethasone were associated most strongly with a decreased risk of haemorrhage whereas labour and vaginal delivery were associated most strongly with an increased risk. These associations remained in a multivariable analysis which included prenatal events (maternal illnesses, fetal presentation and obstetrical interventions), as well as gestational age, birthweight, gender, treatment with assisted ventilation, and the occurrence of pneumothorax. Further aetiological study of the effects of prenatal factors could provide information useful in preventing SEH/IVH. PMID- 1635887 TI - Seasonality of births in Turkey. PMID- 1635886 TI - 'Errors' in perinatal medicine: an epidemiological perspective. PMID- 1635888 TI - Cohort reconstruction. PMID- 1635889 TI - Cryopreserved human tissue in pharmacological research. AB - Despite the relevance of human isolated tissue in human pharmacology, its use is still very much the exception rather than the rule. The major reason for this is that the supply of fresh human material is both irregular and unpredictable. This article considers the usefulness of cryopreservation to store human isolated tissues for subsequent pharmacological studies. Despite certain problems, such as some reduction in contractile force and endothelial function, the main biochemical properties and affinities of most agonists and antagonists have been shown to be well preserved. Hence, this technique offers clear potential for ensuring the supply of both vascular and non-vascular human material for pharmacological studies. PMID- 1635890 TI - Control of salt intake by steroids and cerebral peptides. AB - Steroids (aldosterone and testosterone) and peptides of cerebral origin (angiotensin II and the tachykinins) control the salt intake of the rat. They arouse or suppress the behaviour and produce life-long enhancements of NaCl intake. Need-induced salt intake (salt appetite or salt hunger), which is the consequence of sodium deficiency, is aroused by a synergy within the brain of cerebral angiotensin II and aldosterone. And prior episodes of sodium depletion produce enhancements of subsequent salt appetites, but only if the prior depletions were accompanied by angiotensin II and aldosterone action. Need-free salt intake, which occurs daily when the rat is in positive sodium balance, is inherently high in the rat and is organized in the perinatal period by aromatized testosterone which suppresses the intake of the male. It is also enhanced by prior activations of angiotensin II and aldosterone. Both need-induced and need free salt intake are suppressed by intracranial tachykinins. Non-mammalian tachykinins (eledoisin, physalaemin, kassinin) are both antidipsogenic and antinatriorexigenic, but amino-senktide, an analogue of the mammalian tachykinin substance P with selective affinity for the NK 3 receptor, appears to be a selective antinatriorexigenic agent, and could provide a rational therapy for chronic overconsumption of salt. PMID- 1635891 TI - Effects of S9977 and dihydroergotamine in an animal experimental model for migraine. AB - The present study concerns the effects of S9977, a trimethylxanthine derivative with potential antimigraine characteristics, on the distribution of carotid blood flow in the anaesthetized pig. Furthermore, the effects of dihydroergotamine have been analysed for comparison. Dihydroergotamine (3, 10, 30 and 100 micrograms/kg, i.v.) elicited dose-dependent pressor and bradycardic responses which were probably mediated by its partial agonist action on alpha-adrenoceptors and dopamine2 receptors. In contrast, S9977 (0.3, 1, 3 and 10 mg/kg, i.v.) caused a moderate hypotension and bradycardia. The carotid haemodynamic effects of dihydroergotamine (3, 10, 30 and 100 micrograms/kg, i.v.) consisted of a dose dependent reduction of arteriovenous anastomotic blood flow and conductance and an increase in nutrient (tissue) blood flow and conductance. As a consequence, jugular venous PO2 decreased. These findings, demonstrating an active constriction of arteriovenous anastomoses, are in agreement with earlier findings in cats. Though S9977 (0.3, 1, 3 and 10 mg/kg, i.v.) decreased carotid (two highest doses) and arteriovenous anastomotic (highest dose) blood flow, there was no concomitant decrease in the vascular conductances. Therefore, the effects of S9977 seem to be related to a decrease in arterial blood pressure and not to an active vasoconstriction of arteriovenous anastomoses. These results are discussed in terms of the potential therapeutical usefulness of S9977 in the treatment of migraine. PMID- 1635892 TI - Pharmacokinetics of heptastigmine in rats. AB - Heptastigmine is a new long acting cholinesterase inhibitor that affects behaviour in a number of cognitive tests in animals. We have studied its pharmacokinetics in rats: plasma kinetics were evaluated after single intravenous dose (2 mg/kg), intramuscular (4 mg/kg) and oral (4 and 8 mg/kg) administration. Tissue distribution (heart, liver, kidney and brain) was studied after single intramuscular (4 mg/kg) and oral (8 mg/kg) administration. Plasma and tissue kinetics were also investigated after repeated oral doses (8 mg/kg b.i.d. for 7 days). Heptastigmine levels in plasma and tissues were determined using an HPLC method with an electrochemical detector. After a single dose, heptastigmine remained for a long time in plasma (the terminal half-life was about 12 h), distributed widely in tissues (the volume of distribution was about 61) and brain concentrations were very high (4-22 times those found in plasma). After repeated oral doses, the drug levels increased in plasma and, to a lesser extent, in liver and kidney. PMID- 1635893 TI - Effect of the flavanolignans of Silybum marianum L. on lipid peroxidation in rat liver microsomes and freshly isolated hepatocytes. AB - The effect of several flavanolignans (silicristin, silidianin, silybin and isosilybin) present in silymarin, the extract of Silybum marianum fruits, was tested on lipid peroxidation in rat liver microsomes and freshly isolated hepatocytes. In microsomes lipid peroxidation was generated by ADP/Fe2+ and NADPH. All flavanolignans inhibited peroxidation in a concentration dependent manner. In hepatocytes lipid peroxidation was induced by ADP/Fe3+ complex and cell damage was evaluated as LDH activity released in the medium. The inhibition of the peroxidative process by flavanolignans was also evident in this model, even if with a potency order different from that found in microsomes. In contrast, the effect on LDH release was significant only for silybin and isosilybin, the other compounds being inactive on this parameter. PMID- 1635894 TI - Effect of BN 52256 and other mediator antagonists on ouabain-induced cardiac arrhythmia in a model of anaphylaxis in guinea-pigs. AB - Different mediators released by anaphylaxis seem to be involved in different pathophysiological conditions, including cardiac arrhythmia. Histamine, 5-HT and platelet-activating factor (PAF) could participate in the enhanced arrhythmogenicity during anaphylaxis in guinea-pigs. The threshold dose of ouabain-induced arrhythmia is decreased in actively sensitized guinea-pigs by i.p. administration of ovalbumin. The purpose of the present paper was to investigate the effect of different mediator antagonists. Antagonists of PAF (WEB 2170), histamine (clemastine) and 5-HT (cyproheptadine) in doses of 5.0 mg/kg, 5.0 mg/kg and 0.5 mg/kg, respectively, can increase the threshold dose of ouabain induced arrhythmias signalling an antiarrhythmic effect. A combination of WEB 2170 and clemastine, each of them in inactive doses (2.0 mg/kg and 1.0 mg/kg, respectively) showed a statistically significant antiarrhythmic effect. A combination of the same dose of WEB 2170 and cyproheptadine (0.1 mg/kg) under the same conditions induced an antiarrhythmic effect, too. BN 52256 is a new antiallergic drug synthesized on the basis of a novel concept of combining inhibitory activity against various inflammatory mediators in one molecule. BN 52256 in doses of 20-80 micrograms/kg exhibited a statistically significant antiarrhythmic effect. BN 52256 needed a 12.5-125 fold lower dose to induce the same antiarrhythmic effect compared to the antagonists of PAF, histamine or 5-HT investigated in this study. Depending on the pathophysiological conditions, different mediators seem to be involved in the occurrence of cardiac arrhythmia. A complex inhibition of these mediators could induce a more specific influence on such kinds of cardiac arrhythmias. PMID- 1635895 TI - Effects of soman on norepinephrine uptake and electrically stimulated release from human uterine arteries. AB - The effects of soman on the uptake and electrically induced release of norepinephrine (noradrenaline) from isolated human uterine artery have been investigated. Soman did not alter the uptake of norepinephrine by human uterine artery, but reduced the electrically induced release of norepinephrine from the artery. This reduced norepinephrine release may augment the fall in blood pressure induced by accumulated acetylcholine stimulating muscarinic receptors following cholinesterase inhibition. PMID- 1635896 TI - Catecholamine and serotonin depletion from rat spinal cord: effects on morphine and footshock induced analgesia. AB - Using a methodology that causes a selective degeneration of spinal cord catecholaminergic or serotoninergic pathways but not those of the brain, it has been possible to study more precisely the role played by the spinal cord monoaminergic systems that underly the mechanism through which morphine and endogenous opioids modulate nociceptive inputs. Both noradrenaline (NA) and serotonin (5-HT) appear to be involved: first, the noradrenergic and only subsequently, with higher doses of the opiate, the serotoninergic pathways. PMID- 1635897 TI - Effects of prostaglandins and PAF on the contractility of the bovine ciliary muscle. AB - The present study has investigated the effect of prostaglandins and PAF on the contractility of the bovine ciliary muscle, a tissue involved in the control of aqueous outflow. The results show that the prostaglandins tested (PGI2, its stable analogue Iloprost, PGE2, PGE1, and PGF2 alpha) as well as PAF, were able to contract the ciliary muscle, although with different potencies and efficacies. PGI2 and Iloprost displayed parallel dose-effect curves with upper plateaus that did not differ significantly; however, PGI2 was slightly more potent than Iloprost. This is at variance with what is observed at the level of the platelet prostacyclin receptor. PGF2 alpha was equipotent with the PGEs tested, with a maximal effect not different from either PGI2 or PGEs. PAF was the most efficacious of the compounds tested. PMID- 1635898 TI - Homelessness: a rural perspective. PMID- 1635899 TI - Sounding a political call to arms. PMID- 1635900 TI - ANA position statement on nursing and the Patient Self-Determination Act. PMID- 1635901 TI - Nurses in advanced practice: a new prescription for a healthy America. PMID- 1635902 TI - Fetal alcohol syndrome and its implications for the day care provider. PMID- 1635903 TI - Discharge planning. PMID- 1635904 TI - [Integrated individual psychotherapy of adolescent and young adult enuretic patients--psychodiagnostic and psychosomatic aspects]. AB - The subject of this paper are fundamental positions, concerning the contents, and empirical results of 15 years time, concerning the dynamic-orientated single psychotherapy for youth and young adult enuretics. It is supported by analyses of 15 years time in the medical-psychological practice. From a sample of, all in all, 250 patients, the results of a group of 55 patients at the age of 15-21 years are shown, who were treated with dynamic-orientated single-psychotherapy, and are discussed with an emphasis on the integrative, biopsychosocial character of this illness. Enuresis nocturna is being regarded consequently as a special psychomatic complex phenomenon, and the empiric results are being interpreted with orientation to theory. There have been applied several test-methods for the purpose of inter-groupal pre-post-analyses, before and after the treatment with a duration of katamnese of 6 months. Statements concerning the efficiency, as well as essential changes of parameters in the course of the psychotherapy are special subject of result-related discussions. The results certify, that contential specific, age-differentiated emotional and social aspects of personality and reflexion are getting very significantly changed in the course of the successful or partly successful therapy, while in the cases of the non-successfully treated patients no changes in such manner could be obtained. PMID- 1635906 TI - [Sex differences in dreams. Content analysis of oknophile and philobatic dream images in the dreams of children and adolescents]. AB - Until now it had been observed that in their dreams girls concern themselves more with inter-human relationships, whereas boys concern themselves stronger with the outside world and aggressive striving. In this survey manifest dreams, as reported in psychotherapies, spontaneously remembered and taken down by the children and young people themselves, were examined with an index in which Balint's theories about oknophilia and philobatism were used. The question whether there are any differences of sex was checked there. One important result of this survey was that girls in fact dream more oknophile subjects, whereas boys dream more philobatic ones. As the philobatic attitude might be put down to an earlier trauma than the oknophile one, this result here above all corresponds with the hypothesis of the feminist psychoanalytics (Chodorow, Olivier), that boys axe dismissed from the symbiosis with their mothers too early. With that they get into a premature independence they are not up to. Girls on the other hand are rather overcharged narcissistically and their mothers hold on to them for too long. PMID- 1635905 TI - ["Men only make dirt!"--A study of single mothers in a mother-child program]. AB - This paper deals with social case work of single-parent mothers participating in a 'mother and child' programme in Ulm. The social workers realized that these mothers frequently leave the childrens' fathers immediately after the birth of the baby or soon after. The relationships of the mothers with their partners and their families of origin were studied by questionnaires. The authors find that those women who broke the relationships to the childrens' fathers judge their families of origin as significantly more dysfunctional as those mothers who have been relating to their partners. It is assumed that the single parent mothers suffer from insufficient internalizations with their own fathers in regard to attachment behaviour. Tragically these women repeat the instability of their parents' marriages in their own partnerships. PMID- 1635908 TI - Current topic: water volume of the ovine conceptus; point of view. AB - The sheep is the only species for which there is sufficient information to justify an overview of maternofetal water transfer. Current information points to the following conclusions: (1) the site of water exchange between mother and conceptus is mainly the placenta; (2) the pressure that initiates transfer to the fetus is the osmotic pressure of solutes that are present in higher concentrations in fetal plasma than in maternal plasma, such as urea, fructose, amino acids, bicarbonate and lactate; (3) maternal ultrafiltrate thus attracted into the conceptus arrives there mostly denuded of electrolytes and is strongly hypotonic; thus it is the transfer of electrolyte that restrains the transfer of water; (4) maternofetal transfer of water is strongly facilitated by angiotensin I in the fetal circulation by a sequence of events that has not yet been elucidated; (5) the net combined osmotic and hydrostatic pressure that drives water across the placenta is of the order of only 20 to 80 mm Hg; (6) it is necessary to make a sharp distinction between transfer from mother to conceptus and transfer from one compartment to another compartment within the conceptus. Finally, the review lists certain precautions to be taken in the further study of water exchange between mother and conceptus. PMID- 1635907 TI - [Dangerous comics--only a fantasy?]. AB - Both superhero comics and fairy tales are equally popular with children: they create fantasy worlds full of violence and dangers which the hero must overcome. The question is raised whether the criticism of prevailing violence and a lack of realism can be rejected not only when considering fairy tales but also in the case of comics. The comparison of the two genres leads to the following results: Comics with their regressive pull and their independent superhuman heroes represent the archaic world of narcissism unconscious, unwilling to develop and conservative. Violence serves to maintain the original state or regain a harmonious "paradise". However, the rich world of symbols is also the creative source of our existence to which we keep returning--whether in dreams or in other fields of imagination. As works of literature, fairy tales seem to be more progressive and concerned with solutions. In the main, they support the development of the self. Violence is used to overthrow the old order and usher in the new. The aggression results in overcoming the unconscious. The image of the fairy tale hero corresponds to the child's view of the world. He does not seek narcissistic solitude and greatness but the companionship of prince or princess. A progressive and optimistic view of the future as well as a more conservative and retrospective tendency are part of human nature. For children, however, problems of development take precedence. Thus superhero comics are only dangerous for severely disturbed children, but fairy tales are certainly more beneficial. PMID- 1635909 TI - Effects of diacylglycerol and gonadotropin-releasing hormone on human chorionic gonadotropin release by cultured trophoblast cells. AB - The effect of activation of calcium- and phospholipid-dependent protein kinase (protein kinase C) on human chorionic gonadotropin (hCG) release by cultured trophoblast cells was studied and a role of protein kinase C in the GnRH-mediated hCG release was also evaluated. Both GnRH and 1-oleoyl-2-acetylglycerol (OAG), a protein kinase C activator, stimulated hCG release after 3 h incubation in a dose dependent manner with ED50 of 55 nmol/l and 4.0 nmol/l, respectively. A tumor promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) also stimulated hCG release while two non-tumor-promoting compounds, phorbol and 4 alpha-phorbol, failed to stimulate hCG release. hCG release by maximal effective dose of GnRH (10 mumol/l) or OAG (1 mumol/l) was further stimulated when cells were incubated with same concentrations of GnRH and OAG. OAG-stimulated hCG release was completely inhibited by a protein kinase C inhibitor, H-7, with ID50 of 23 nmol/l while H-7 did not affect GnRH-mediated hCG release. These results indicate that GnRH-stimulated hCG release is not mediated by protein kinase C pathway, however, the secretion of hCG is also regulated by the mechanism that involves protein kinase C activation. PMID- 1635910 TI - Placental localization of 15-hydroxy-prostaglandin dehydrogenase in early and term human pregnancy. AB - The human placenta possesses a large capacity for inactivation of prostanoids. This is due to the presence of large quantities of the NAD(+)-linked 15-hydroxy prostaglandin dehydrogenase (PGDH type I; EC 1.1.1.141). In order to investigate whether a specific localization of PGDH is at the origin of the increasing placental PGDH activity during early pregnancy, PGDH activity was localized histochemically in placental tissue obtained in early pregnancy and at term. Intracellular PGDH activity was present in three distinct compartments in the placenta. First, the syncytiotrophoblast and second, the underlying cytotrophoblast layer of placental terminal villi contained PGDH. Third, scattered throughout the sections, we found chorion-like cells which showed strong staining for PGDH activity. The intensity of staining in samples before 12 weeks of gestation was much less than in samples after 12 weeks of gestation, which were comparable to those at term. Thus, the fetal cell layers at the boundary between the fetal tissues and the maternal blood have a great potential to inactivate prostanoids suggesting that the fetus protects itself against prostanoids of maternal origin. PMID- 1635911 TI - Effect of maternal hypokalaemia on unidirectional maternofetal and net potassium fluxes across the placenta of the anaesthetized rat. AB - Potassium (K+) fluxes across the placenta of rats, at 21 days gestation, fed a low K+ diet or a control diet were studied. The rats on the low K+ diet had a significantly (P less than 0.001) lower arterial plasma K+ concentration compared to those on the control diet (1.95 +/- 0.12 and 2.93 +/- 0.06 mmol/l respectively; mean +/- s.e., n = 17). Fetal umbilical arterial plasma K+ concentration was unaltered in maternal hypokalaemia and was significantly (P less than 0.001) higher than that of maternal plasma (4.58 +/- 0.15 and 4.66 +/- 0.12 mmol/l in low K+ and control groups respectively). Net K+ flux across the placentas (as measured by fetal accretion between days 20 and 21 of gestation) of hypokalaemic mothers (0.106 +/- 0.02 mumol/min/g placenta, n = 6) was not different to that in controls (0.104 +/- 0.01 mumol/min/g placenta, n = 8). Unidirectional maternofetal flux (Jmf) across the placentas, measured as the accumulation of 42K in the fetuses after injection of the radioisotope into maternal blood, was also not significantly different between the hypokalaemic and control mothers (0.5 +/- 0.08 mumol/min/g placenta, n = 8 versus 0.63 +/- 0.06 mumol/min/g placenta, n = 7, respectively). However, measurement of Jmf by perfusion of the placentas through their fetal circulations yielded a higher value than the accumulation method and in this analysis was significantly (P less than 0.02) lower in the low K+ than in the control group (0.75 +/- 0.10 mumol/min/g placenta, n = 11, and 1.27 +/- 0.14 mumol/min/g placenta, n = 9, respectively). These results show that net placental K+ fluxes are unaltered during maternal hypokalaemia but suggest that unidirectional maternofetal fluxes may be reduced. PMID- 1635912 TI - Plasma levels of eosinophil granule major basic protein in pregnant cynomolgus monkeys. AB - The sera of all pregnant women contain increased amounts of a protein biochemically and immunologically similar to the eosinophil granule major basic protein (MBP). Immunofluorescence shows that the pregnancy-associated MBP is localized to placental trophoblastic cells. This information raises important questions about the function of pregnancy-associated MBP because of the potential biological functions attributed to its eosinophil counterpart (namely, its potent toxic and cytostimulatory activities). Previous studies demonstrated the presence of an immunologically cross-reactive protein in the placentae and plasma of pregnant non-human primates. Here, plasma MBP levels were measured throughout gestation in cynomolgus monkeys. In early pregnancy, only modest increases in MBP were found in contrast to the sharp rise observed in the first 20 weeks of human pregnancy. During the final one-third of gestation, striking increases in plasma MBP occurred in the monkeys. This parallels the late rise in MBP seen in humans in the third trimester. Thus, the cynomolgus monkey may serve as a model to clarify the role of the MBP in the biochemical events that culminate in parturition. PMID- 1635913 TI - Enhanced glutathione S-transferase (GST) activity in pregnant rats treated with benzo(a)pyrene. AB - Administration of Benzo(a)pyrene (BP, 50 mg/kg/d) to pregnant rats significantly increased Glutathione S-transferase (GST) activity in placental tissue-extract (Vmax = 40 nmol/min/mg protein and 69 nmol/min/mg protein in controls versus treated animals respectively; P less than 0.01) and total fetal tissue-extract (Vmax = 51 nmol/min/mg protein and 82 nmol/min/mg protein in controls versus treated animals respectively; P less than 0.01) indicating an induction effect of BP on the GST system. An increase in the Km values was also observed: 1.61 x 10( 3) M and 2.84 x 10(-3) M in control versus treated placentae; 1.38 x 10(-3) M and 2.05 x 10(-3) M in control versus treated fetuses. A competitive effect on the enzyme by the BP present in the sample may also be involved. The glutathione content in both tissues did not show any changes after the treatment with BP. This increase in the GST system was not sufficient to protect the fetus. BP affected the reproductive performance of pregnant rats by significantly increasing the number of resorptions and fetal wastage, and, also, by decreasing the fetal weight. PMID- 1635914 TI - Endotoxin induced intraplacental thrombotic tendency and decreased vascular ADPase in the pregnant rat. AB - The mechanism underlying increased sensitivity for endotoxin in pregnancy, as reflected by intravascular thrombus formation in various organs i.e. the placenta, is unknown. We studied the influence of endotoxin infusion at day 14 upon the vascular antithrombotic ADPase present in the labyrinth of the rat placenta just before term (day 21). Pregnant Wistar rats were infused with either endotoxin (1 microgram/kg body weight) or saline through permanent vena jugularis catheters and their placenta and kidneys were examined at day 21 using light electron microscopy and enzyme cytochemistry at the ultrastructural level. Also, placenta perfusion ex vivo was done using platelets and ADP to test the thrombotic tendency of placental vessels in endotoxin treated and control rats. The results show in both maternal as well as the fetal vessels of the placental labyrinth vascular occlusions and decreased membrane ADPase activity exclusively in endotoxin treated and not in saline infused pregnant animals. Alternate placenta and kidney perfusion ex vivo resulted in intraplacental and intraglomerular platelet aggregation again exclusively in endotoxin-treated rats. It is concluded that vascular ADPase may be affected by endotoxin due to the pregnant condition, resulting in a functional defect in antithrombotic potention which may promote intravascular formation of microthrombi in situ. PMID- 1635915 TI - The route of maternal IgM transport to the rabbit fetus. AB - The route of IgM transport to the rabbit fetus was investigated by comparing its localization with that of IgG in the yolk sac splanchnopleure and uterine tissues using direct immunofluorescence and immunodiffusion analysis. IgM was first detected in fetal serum at 20 days of gestation but was present in uterine fluid at 18 days, the earliest stage tissues and fluids were examined. IgM was co localized with IgG in the yolk sac endoderm basement membrane and in the vascular mesenchyme of the yolk sac splanchnopleure providing evidence of its transport to fetal blood; it was also present in vesicles in the yolk sac endoderm. IgM could not be detected in uterine fluid of nonpregnant uterine horns of rabbits unilaterally pregnant. Human IgM injected into the maternal circulation was readily transported to the uterine fluid and across the yolk sac splanchnopleure to fetal blood indicating that IgM secreting plasma cells, found to be present in the uterine stroma, contributed little towards IgM in the uterine fluid. Degenerating paraplacental decidual tissue, a feature of rabbit pregnancy, is suggested to be a major route for maternal immunoglobulin transport to the uterine fluid. PMID- 1635916 TI - Microdetermination of vitamin D2 (ergocalciferol) using N-bromosuccinimide. AB - A novel method for the microdetermination of vitamin D2 in its pure state and pharmaceutical preparations using N-bromosuccinimide (NBS) is reported. The new method is easy, simple, and accurate. PMID- 1635917 TI - [Relationships between manufacturing parameters and pharmaceutical-technological requirements of biodegradable microparticles. 2. Preparation of injectable microparticles in biodegradable polyester]. AB - Local anesthetics containing biodegradable polyester microparticles are prepared using a modified solvent-evaporation process and a spray drying technique. The preparation methods are compared critically. The modified solvent-evaporation process is preferred for the preparation of microparticles. Yields of 90% and microparticle size distributions can be influenced in a reproducible manner. Using the spray drying technique yields are only 60%. The product is characterized by a high portion of microparticles under 10 microns, which are responsible for the rapid release of cinchocain in 168 h as well. PMID- 1635918 TI - Timolol in lipospheres. AB - Lipospheres carrying timolol (1) were obtained from microemulsions. They had lecithin, palmitic and decanoic acids as the main constituents. The sizes were between 300 and 400 nm and the amount of 1 incorporated varied from 2.7 to 4.8% according to the microemulsion used. Compound 1 was present in the lipospheres mainly as ion pairs in order to increase its lipophilicity. The difference found in the incorporation was principally due to the different lipophilicity of the ion pairs of 1. PMID- 1635919 TI - [The use of bead cellulose for controlled drug liberation. 5. Binding of benzocaine as a model drug to dialdehyde-bead cellulose and its in vitro liberation]. AB - In the case of ionic binding of drugs to bead cellulose and its derivatives there was no pronounced retardation obvious. Because of this lack benzocaine as a model drug was covalent bound to dialdehyde bead cellulose by an azomethine bond in analogy with enzyme immobilisation methods. The rate of liberation in phosphate buffer was low and incomplete compared with the dissolution rate of pure benzocaine under the same conditions. A further decrease of liberation rate was obtained by reduction of the azomethine to the amine bond. Retardation of drug liberation strictly speaking was not achieved. The main amount of liberated drug was liberated during the first 20 min, but after 6 h the rate was still under 50% of the drug available. The physical properties of the beads like spherical shape and porosity are not significantly influenced by oxidation of cellulose and by loading with drug. PMID- 1635920 TI - Regulation of the tetracycline hydrochloride release from polyacrylate microspheres. Part 1. AB - Due to the precipitation of free bases sparingly soluble in water, it is not possible to achieve a uniform release in the gastrointestinal tract of delayed action drugs containing salts of weak bases, e.g. tetracycline hydrochloride, at pH-values surpassing their pKa values. The problem of drug release control can be solved by adding Eudragit L to the polymetacrylate (Eudragit RS) microspheres. It has been established that 30% Eudragit L ensures a gradual uniform release of tetracycline hydrochloride (KOr = 11%/h) irrespective of variations in the pH of the gastrointestinal tract. PMID- 1635921 TI - Some factors affecting properties and dissolution behavior of tableted furosemide microspheres. AB - Furosemide (1) microspheres prepared by using Eudragit RS (1:4 and 1:2 drug:polymer ratios) were tableted. Microspheres were compressed with or without excipients (lactose, Avicel PH 101 or Emcompress). The thickness and crushing strength of tablets containing excipients were also found to be affected by the type of excipients. Dissolution characteristics of furosemide from tableted microspheres with or without excipients depended on the applied compression force but showed a controlled release behavior. Compression slowed down the release of 1. Addition of excipients to the formulation increased drug dissolution. The release from tablets followed Higuchi matrix model kinetics. PMID- 1635922 TI - Studies on dressing for dental surgery use. Part 2. Influence of Kunitz' protease inhibitor on properties of dental gelatinous dressings. AB - To increase resistance of gelatinous dressings to the etching action of trypsin in vitro, the Kunitz' protease inhibitor has been added. It has been found that the etching rate of the dressings was reduced in proportion to the inhibitor added. Addition of plasticizers in the presence of an inhibitor reduces the etching rate of the dressings and the effect depends on the type and concentration of the plasticizer added. Thermally sterilized dressings have an average of 10% less resistance to the etching action of trypsin. The liberation of the inhibitor from the dressings follows first order kinetics, whereas its liberation rate depends upon the type of the plasticizer used. PMID- 1635923 TI - Effect of AWD 52-39 on vasoconstriction induced by noradrenaline and 5 hydroxytryptamine in vitro and in vivo in rats. AB - The vascular effect of the potential nootropic AWD 52-39 (1; N,N-diacetoxyethyl 9,10-dihydrolysergic acid amide) as well as its influence on noradrenaline- or 5 HT-induced vasoconstriction were studied in the isolated rat aorta and in anesthetized normotensive and pithed rats. Vasoconstriction was determined by measuring the increase in mean arterial pressure (MAP). Both in vitro and in pithed rats, 1 caused a slight vasoconstriction, whereas a dose-dependent short lasting decrease in mean arterial pressure was found in normotensive rats. In vitro and in pithed rats, 1 exerted no influence on the noradrenaline-induced vasoconstriction, while the 5-HT-induced contractile response was significantly inhibited. These findings characterize 1 as a competitive antagonist at vascular 5-HT2 receptors without any alpha-adrenolytic effect. PMID- 1635924 TI - Immunological and antitumor effects of coumarin and some derivatives. AB - Coumarin and its 4-OH and 7-OH derivatives, as well as o-, m- and p-coumaric acid were tested against P-815 and P-388 tumor cells in vitro. In addition, the compounds were investigated in various in vitro immunological test systems and genuine coumarin was tested furthermore against the Sarcoma-180 in CD1 mice. In vivo, coumarin showed only a moderate antitumor effect against the allogeneic Sarcoma-180 at concentrations of 10 and 40 mg/kg, with inhibition rates of 49 and 60%, respectively. However, both concentrations were markedly toxic. In vitro all compounds were more or less cytotoxic against P-815 and P-388 tumor cell lines starting at a concentration of 100 micrograms/ml. At subtoxic concentrations (less than or equal to 10 micrograms/ml) the samples showed no mitogenic activity against murine spleen lymphocytes and PHA costimulated human peripheral blood lymphocytes. Furthermore, with the coumarin derivatives neither cytotoxic macrophages could be induced against P-815 tumor cells nor an increased release of Il-2 and TNF-alpha could be observed. Only 7-OH coumarin, in concentrations of 2 and 20 micrograms/ml, caused a strong increase in phagocytosis of 124 and 84% in both, human peripheral blood granulocytes and murine peritoneal macrophages, respectively. PMID- 1635925 TI - [Sex as a factor in drug consumption]. AB - Based upon the hypothesis on the diverse dependency of drug consumption on the sex of population as its influencing factor, this relationship was closely studied. The dynamics of the dependency of large urban population has been analysed for a period of 4 years. Important differences in the dependency on sex and age have been found. The fine structure of this dependency including the analysis of its stability have been determined. The experiment was based on mathematical analysis methods. PMID- 1635926 TI - Stability of meclofenoxate hydrochloride in artificial gastric and intestinal media. PMID- 1635927 TI - [Calmus as a drug: advantage or risk?]. PMID- 1635928 TI - Synthesis and in vitro study of platelet antiaggregant activity of some 4 quinazolinone derivatives. AB - Some new 4-quinazolinones were prepared. Their antiplatelet activity was evaluated in vitro with respect to aggregation induced by ADP, collagen, arachidonic acid and the platelet serotonin release reaction. Most molecules showed an inhibiting power similar to that of acetylsalicylic acid under the same conditions, and even greater when aggregation was induced by ADP. Reduction of the 4-quinazolinone derivatives to their 1,2,3,4-tetrahydroquinazoline homologues produced an increase in platelet inhibitory action except when ADP is the inductor. PMID- 1635930 TI - Mechanism of the polarographic reduction of a new 5-nitrofuran derivative with antibacterial activity. AB - The reduction at mercury electrodes of a new 5-nitrofuran derivative with antibacterial activity, N2-(5-nitrofurfurylidene)formohydrazide-4-(3,5 dicyanophenyl)-6-ethoxy-2- pyridyl)imide, was studied by conventional, normal pulse, reverse normal pulse and differential pulse polarography in water dimethylformamide (30%) buffered media. The waves observed, whose number depended on pH, are attributed to the reduction of the nitro group (6 electrons) and the azomethinic unit (4 electrons). The basic mechanisms of the electrode reactions have been deduced from the characteristics of the waves. Conditions for determining the formal potential of the nitroderivative/radical-anion system, a parameter related to pharmacological activity, are also reported. PMID- 1635929 TI - Study of local anaesthetics. Part 98(3): Preparation and local anaesthetic activity of 4-alkylpiperazinoethyl esters of o-heptyloxyphenylcarbamic acid. AB - During the course of study of variations in the basic moiety of heptacainium chloride 10 derivatives of 4-alkylpiperazinoethyl esters of o heptyloxyphenylcarbamic acid were prepared. Pharmacological investigation indicated that practically all the new compounds were several times more active than standards (cocaine and procaine). The most effective compound was 1-[2-(o heptyloxyphenylcarbamoyloxy)ethyl]-4-butyl-piperazinium dichloride, which was 142 times more active than cocaine and 266 times more active than procaine. PMID- 1635931 TI - Proof of efficacy of nootropics for the indication "dementia" (phase III)- recommendations. PMID- 1635932 TI - TSH responses to TRH as a function of basal serum TSH: relevance for unipolar depression in females--a multivariate study. AB - Baseline thyroid-secreting-hormone (TSH)-assessed by means of ultrasensitive assays (IRMA)-and free-thyroid-hormone (FT4) levels were determined in 84 depressed females, and the TSH responses to 200 micrograms thyrotropin-releasing hormone (TRH) (IV) measured. It was found that TRH-induced TSH responses were linearly and positively related to basal TSH-IRMA; lower TRH-stimulated TSH secretion in melancholic patients was attributable to lowered basal TSH-IRMA values. A progression was found-within the euthyroid range-of basal TSH-IRMA values towards lower levels along the diagnostic spectrum: the highest basal TSH IRMA levels were witnessed in minor depressives and the lowest in melancholics, while simple major-depressed females occupied an intermediate position. This shift appears to be indicative of severity of illness. Basal TSH-IRMA data can roughly be used as a clinical tool separating melancholia from minor depression: at a threshold value of less than or equal to 1 microUI/ml, sensitivity was 56% and specificity 92%. It is concluded that basal TSH-IRMA provides a more accurate representation of melancholia than peak TSH responses, which appear to constitute little more than a magnified, but biased signal of basal TSH-IRMA. In future, the assay of basal TSH-IRMA could replace TRH testing. PMID- 1635933 TI - A comparison of carbamazepine Divitabs and a normal carbamazepine preparation in psychiatric and oligophrenic patients. AB - Twenty patients who had become accustomed to a stable oral carbamazepine dose participated in an open, randomized, two-centre, cross-over study, in which ordinary tablets and Divitabs (a new sustained release preparation) were compared. Pharmacokinetic parameters, seizure control, effects on the behavioral state, and tolerability were considered. A smaller Area Under the Curve (AUC) during the Divitabs period was the only pharmacokinetic parameter with a significant difference (p less than 0.05). However, all patients with peak/trough carbamazepine serum level ratios of at least 1.30 after the intake of the normal tablet-form (n = 9) showed a smaller peak/trough ratio during the Divitabs period. No remarkable differences were found between the normal carbamazepine preparation and Divitabs regarding seizure frequency and tolerability. The behavioral state improved in four patients during the Divitabs period, whereas no enhancement was noticed during the normal-tablet period in any of the subjects. Although this study produced no evidence that carbamazepine Divitabs were at all advantageous for the trial population in general, some of the pharmacokinetic results suggest that a subgroup of the patients would benefit from changing from the normal tablet-form to Divitabs. However, even in this subgroup, the usage of Divitabs was not shown to result in obvious clinical benefits. PMID- 1635934 TI - Monitoring of laboratory parameters during carbamazepine therapy in psychiatric patients. AB - In recent years, carbamazepine has increasingly also been used in psychiatric indications. However, the manifold action of this drug also manifests itself in a number of adverse effects. In a prospective study including 46 patients, who were given carbamazepine for psychiatric indications and most of whom were also treated with one or several other psychotropic drugs, the following laboratory parameters were determined at two-weekly intervals: red and white blood count, platelets, SGOT, SGPT, gamma GT, alkaline phosphatase, serum calcium, serum sodium, IgA, IgG, IgM. Statistically significant changes were found in erythrocytes, leucocytes, platelets (decrease), Gamma GT (increase), serum calcium (decrease), IgA, IgM (decrease). The clinical relevance of these changes is discussed. PMID- 1635935 TI - The antidepressant effect of carbamazepine in callosal agenesis: a case report. AB - A dramatic resolution of severe depressive symptoms following carbamazepine administration in a patient with callosal agenesis is reported. Maintenance treatment with carbamazepine resulted in the alleviation of concomitant organic symptoms and in a marked improvement in quality of vital functions. PMID- 1635936 TI - Effect of pyritinol on EEG and SSEP in comatose patients in the acute phase of intensive care therapy. AB - The extent and duration of acute disturbances of consciousness depend on the severity and localization of the underlying cerebral dysfunction. The Glasgow Coma Scale (GCS) permits a relevant statement to be made on the course and recovery tendency of functional damage patterns in cerebral, mesencephalic, and brain stem structures. Therapy is directed at exerting a beneficial effect on the disturbed cerebral metabolism by administration of centrally active substances and at utilizing the available reserve plasticity of the brain for any possible recovery of mental performance. The bioavailability and profile of action of pyritinol have been well documented in animal experiments. We have studied the question as to the extent to which the substance influences the depth of coma in patients receiving acute intensive care therapy, and how this can be objectified electrophysiologically in the form of a specific central effect on basal brain structures. In a phase-II pilot study over five days the acute effect of intravenous 60-min. administration of 1,000 mg pyritinol on the depth of coma, the central conduction time (CCT) and the primary complex amplitude (N20/P25) of the SSEP, and on vigilance behavior (spectral edge frequencies and power) was investigated for 90 minutes in each case under intensive-medical steady-state conditions in 10 comatose patients. Because of the differences in the underlying brain damage, the primary depth of coma, age (30-89 years), sex (two female, eight male), as well as previous treatment (surgery, conservative), the significance of the results could not be evaluated by confirmatory statistical analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635937 TI - Efficacy of low vs. high doses of levosulpiride on negative symptoms of schizophrenia. PMID- 1635939 TI - Believe it or not! PMID- 1635938 TI - Negative attitudes towards clinical trials: problem or promotion? PMID- 1635940 TI - Differences in developmental movement patterns used by active versus sedentary middle-aged adults coming from a supine position to erect stance. AB - The purpose of this study was twofold: (1) to further validate categories for the movement pattern of supine to standing in adults and (2) to evaluate the influence physical activity might have on the movement patterns used for rising. Seventy-two adults, between 30 and 39 years of age (mean = 34.1, SD = 2.8), performed the rising task while being videotaped. Subjects were divided into three groups by self-reports of level of physical activity (daily to rarely). Individual videotaped trials were classified using the previously described categories. Comparisons among the activity-level groups revealed that more active subjects demonstrated more developmentally advanced movement patterns in the righting task, consistent with earlier research on older adults. Results suggest that lifestyle patterns of regular, moderate physical activity may influence how a person performs the basic righting task of coming from a supine to a standing position. This investigation also provided additional support for the use of developmental sequences for the movement pattern of supine to standing. PMID- 1635941 TI - Direct access use by experienced therapists in states with direct access. AB - Direct access use among experienced therapists practicing in states with 3 years' experience with direct access was studied, as were differences between therapists who had and had not practiced through direct access. A questionnaire was mailed to 250 members of the North Carolina, Nevada, and Utah chapters of the American Physical Therapy Association. Almost half (44.5%) of the respondents had practiced through direct access; an estimated 10.3% of their caseload was seen through direct access. Reasons for not practicing through direct access were that the employer does not permit direct access practice (49.1%), insurance does not reimburse for direct access practice (43.6%), no patients have been seen without referral (25.5%), and personal preference to treat by referral only (23.6%). Therapists who had treated patients through direct access were significantly more likely to believe that direct access had benefited them professionally and benefited their patients than were therapists who had not practiced through direct access. PMID- 1635942 TI - Influence of sensory inputs on standing balance in community-dwelling elders with a recent history of falling. AB - Vision and/or ankle somatosensory inputs often do not correlate with the position of the center of gravity. In this case, visual or somatosensory information may be in conflict with other sensory systems that convey a true sense of body orientation. The purpose of this study was to determine how conflicting visual and ankle somatosensory inputs influenced standing balance in elders with a history of falls. Forty-seven community-dwelling elders (8 male, 39 female), between 65 and 96 years of age (mean = 80.5, SD = 9.0), participated in this project. Subjects with two or more falls in the 6 months prior to study were assigned to a fall group (n = 16), whereas those with no history of falling during the same time interval were assigned to a no-fall group (n = 31). In order to remove any bias in the testing procedure, the tester was not aware of group assignments. Subjects were evaluated using a sensory organization test (SOT) for standing balance and a "Get Up and Go" test (GUGT) for general mobility. Analysis of covariance was used to evaluate the SOT scores (by group, vision, and surface condition) and the GUGT scores. Body sway is known to increase with the normal aging process, and for this reason, age was selected as a covariate. The association between the SOT total score and the GUGT score was evaluated using Spearman rank-order correlation coefficients. The results showed a significant interaction between group and surface conditions, which indicated a decreased stance duration for fallers on a compliant surface compared with the stance duration for nonfallers (adjusted mean faller stance duration = 53 seconds, SD = 42; mean nonfaller stance duration = 67 seconds, SD = 32). Subjects in the fall group also had significantly higher GUGT scores (which indicated poor mobility function) than did subjects in the nonfall group (adjusted mean faller GUGT score = 2.65, SD = 1.48; mean nonfaller GUGT score = 1.47, SD = 0.77). The Spearman correlation between total SOT scores and the GUGT scores was greater for fallers (r = -.67) than for nonfallers (r = -.44). Orientation input from the ankle appears to have greater importance for preventing falls compared with a visual reference. The SOT and GUGT may be useful in the field to establish criteria for screening elders in a fall-prevention program. PMID- 1635943 TI - A new method for the determination of the characteristic shape of an isokinetic quadriceps femoris muscle torque curve. AB - It has been suggested that visual analysis of isokinetic quadriceps femoris muscle torque curve (TC) shapes may have potential use in the diagnosis and prognosis of knee pathologies. The primary purpose of this pilot study was to develop a method for analyzing the shape of an isokinetic TC. Our method normalizes and averages the TC, and then uses curvilinear analysis of the TC shape to aid in diagnosis and prognosis. For demonstration, the method was applied to isokinetic quadriceps femoris muscle TC data collected using a LIDO digital dynamometer from 25 healthy volunteer subjects and retrospectively acquired from the uninvolved limbs of 37 patients with unilateral knee pathologies. The preliminary results revealed (1) that a common quadriceps femoris muscle TC shape existed for the volunteer group at 60 degrees and 180 degrees/s; (2) that the uninvolved limbs of the patient group exhibited the same shape at 60 degrees/s, but not at 180 degrees/s; and (3) that the quadriceps femoris muscle TC shape demonstrated no significant differences with respect to limb dominance or gender for either group. Further testing of this quantitative method on a larger sample is needed to determine its usefulness in the analysis and implications of TC shape concerning pathology and diagnosis. PMID- 1635944 TI - Physical therapy assessment and treatment protocol for nursing home residents. AB - This article describes a standard protocol for assessing physical function in elderly nursing home residents. Major physical dimensions that are measured with the protocol include range of motion, muscle force, muscle reflex activity, sensation, soft tissue status, balance/coordination, and posture. A practical, functionally prioritized treatment model based on the assessment is also presented. The standardized assessment and treatment plan may be useful to the physical therapist in (1) planning and prioritizing treatment, (2) identifying when goals have been met, (3) recognizing when there is a need for treatment plan modification, and (4) educating physical therapy students in applying problem solving skills in their treatment sessions. PMID- 1635945 TI - In support of student research. PMID- 1635946 TI - More support for student research. PMID- 1635947 TI - Physical therapy evaluation is crucial. PMID- 1635948 TI - Reliable ultrasound transmission. PMID- 1635949 TI - [Individualized psycho-educational therapy concept in inpatient treatment of schizophrenic patients--models and personal experiences]. AB - A brief review of literature concerning educative methods of therapy of schizophrenics and their relatives will be used to discuss the similarities of these strategies, which differ in conception and intensity but are comparable considering their efficiency. A self-developed (eclectical) model of educative therapy and first experiences will be introduced. In view of the recessing character resp. the tendency towards chronicity in many cases of schizophrenia it seems, that the improvement of coping-abilities of the patients and their relatives dealing with the disease is a more promising goal concerning the long term prognosis than focussing on "healing" or suppression of actual symptoms. In addition to information about the disease the individualized proceeding corresponding with the person's own experiences will be stressed. Only as far as the concept of disease is close to the one the patient has, it can become relevant for deeds. PMID- 1635950 TI - [A psycho-educational family group for reducing stress and preventing recurrence for families of schizophrenic patients. Catamnestic results of the Tubingen family project]. AB - Providing information about the disease and the way of coping with it has a central position in therapeutic interventions with families. By giving basic knowledge about schizophrenia to relatives we developed the practical conception of the psychoeducative relatives' group (information-group), a structured program, which is oriented toward concrete problem-solving and supportive behavior to cope with stress in the family. The effects of this group were investigated on the knowledge and subjective distress of 35 relatives related to the course of schizophrenia in comparison to a communication group. The participants of the information-group retained their knowledge after 9 months and their distress was decreased significantly. The relapse rate was reduced to 25%. The subjective distress correlated up to .41 with relapse after 9 months. A survey of the patients showed 70% improvements of the symptoms, 75% felt themselves better accepted by relatives. With the development of the relatives' distress scale a suitable instrument to measure distress is available. PMID- 1635951 TI - [Practical importance of the expressed emotion concept for rehabilitation]. PMID- 1635952 TI - [Treatment of schizophrenia in the family]. AB - The Bonn project "Treatment of schizophrenia in Family" is in the tradition of behavioristic and psychoeducative family intervention studies in England and USA. Information about psychosis and its neuroleptical treatment, communication and problem solving training are provided to schizophrenic patients and to their relatives at home. Important results and experiences of the 2-year-study are presented. PMID- 1635953 TI - [Travel as a stabilizing factor in folie a deux?]. AB - Case report on a folie a deux (double insanity) in a relatively young, married couple who decompensated psychologically subsequent to the failure of different compensation mechanisms after premorbid strange behaviour and jointly developed delusions of ugliness and of injury. The history of the disease pattern of "folie a deux", or double insanity, is described, as well as the present-day definitions, and the case report is set against this background. PMID- 1635954 TI - [A nose in the face]. PMID- 1635955 TI - Guidelines for reducing the risk of disease transmission in the psychophysiology laboratory. SPR Ad Hoc Committee on the Prevention of Disease Transmission. AB - The acquired immunodeficiency syndrome (AIDS) pandemic has highlighted the need for safeguards against the inadvertent transmission of infectious disease in the psychophysiology laboratory. These Guidelines identify factors contributing to the risk of bloodborne disease transmission to subjects or technicians, and recommend procedures to minimize such risk, given current knowledge and techniques. The lowest risk is associated with the application of devices, such as surface electrodes, to nonabraded, intact skin. Such devices should be clean, but do not require disinfection. The potential risk of infection is higher when surface electrodes are applied to non-intact skin. Abrasion, or other breaks in the skin, can allow seepage of blood products carrying such pathogens as hepatitis B virus and the human immunodeficiency virus that causes AIDS. Thus electrodes require high-level disinfection before reuse on non-intact skin. In addition, technicians should wear gloves during skin preparation and should abrade the skin no more than necessary, using only sterile, preferably non-sharp materials. The highest risk is that associated with items that enter sterile tissue, such as subdermal electrodes and the needles and lancets sometimes used in skin preparation. Such items must be sterile at the time of use and must be handled with extreme caution. PMID- 1635956 TI - Autonomic correlates of illness imagery. AB - Psychophysiological responses to imagery of self-relevant illness threats were examined for high and low extreme groups of hypervigilants and health care utilizers. Heart rate, skin conductance, and respiration were the physiological measures recorded; self-reports of perceived illness vulnerability, negative affect, image clarity, and image realness were the psychological measures obtained. Responses to neutral, exercise, and illness threat scenes were compared. Hypervigilants showed an increased heart rate response to imagery of illness scenes, whereas all other groups returned more quickly to baseline levels. The results are similar to those reported by Lang for snake phobics. They also lend some support to Horowitz's theory of intrusive imagery, in which self relevant, anxiety-provoking events tend to continuously intrude upon one's thoughts, and this intrusive imagery was reflected cardiovascularly. There could be several possible underlying mechanisms for these findings. PMID- 1635957 TI - Modulation of slow cortical potentials by instrumentally learned blood pressure responses. AB - We assessed whether instrumentally-learned pressor responses inhibit electrocortical activity, as predicted by learning theories of idiopathic hypertension. Subjects received beat-by-beat feedback for increases and decreases in mean arterial pressure measured from the finger (Penaz method). Slow potentials were recorded from the midsagittal line during the final training session. Also recorded at this time were heart rate, eye movements, respiration, and post-session verbal reports of the subject's control strategies. Thirteen of 14 subjects differentiated blood pressure increases and decreases at p less than .05 or better during the final session (within-subject discriminative operant procedure). Slow potentials were less negative on blood pressure increase compared to decrease trials at all midsagittal sites (p less than .02), indicating relative cortical inhibition by pressor responses. This effect occurred even though subjects reported tensing of muscles on increase trials (p less than .01), a behavioral activity previously associated with augmented rather than diminished cortical negativity. On increase trials slow potentials shifted toward positivity just prior to heart rate deceleration (the latter effect confirming activation of the baroreceptors). PMID- 1635958 TI - PRES: the controlled noninvasive stimulation of the carotid baroreceptors in humans. AB - To study physiological and psychological effects of baroreceptor activity, the cervical neck cuff technique has been frequently used to stimulate the carotid baroreceptors mechanically. Using this technique, no satisfying control conditions to date have been available. Because the carotid stretch receptors are sensitive not only to the pressure level, but also to the rate of change, it is possible to manipulate the receptor firing through changes in carotid pulse amplitude. The device described here relies on the application of short changes in cuff pressure tied to different phases within the cardiac cycle (phase related external suction (PRES)). A brief external suction during systole has potent stimulatory effects on baroreceptors whereas the application of the very same pressure pulse during diastole inhibits the firing burst associated with the pulse wave. To allow an ongoing period of stimulation, a sequence of alternating negative/positive pressure pulses is applied. In the stimulation condition, the R wave of the electrocardiogram triggers a negative pulse which is followed by a positive one during diastole. In the control condition this relationship is reversed. Two experiments are reported confirming different baroreceptor effects of the two conditions. PRES allows for blind or double-blind experiments to investigate effects of baroreceptor activity on physiology and behavior. PMID- 1635959 TI - The relationship between cardiovascular and catecholamine reactions to laboratory and real-life stress. AB - Studies on the predictive value of stress testing in the laboratory for the reaction to real-life stress have shown equivocal results. The variety of laboratory tasks differ for unknown reasons in their predictive power, and the results vary unsystematically among the physiological parameters measured. Most studies have focused on the prediction of ambulatory levels of blood pressure. Many other influences, besides stress, however, influence ambulatory levels. Therefore, a better operationalization of real-life stress is to measure a person in a resting position during a period of well defined real-life stress. The present study investigates whether the difference in ability of laboratory stress tasks to predict real-life stress values is due to the different type of physiological response they induce. Hence, in the present study a more detailed measurement of the stress response was performed. A second question was whether stress testing would add to the prediction of the real-life stress reactions above the prediction based on resting levels. This question was answered for both cardiovascular and catecholamine reactions to laboratory tasks. Two active coping tasks, one inducing a mainly cardiac-sympathetic reaction and the other a relatively more vascular response, and a cold pressor test were administered to 33 healthy young males. Real-life stress consisted of the anticipation of the public defence of the PhD thesis. Tasks indeed differed in predictive power, but this was not a function of the type of response they induced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1635960 TI - Dimensional analysis of no-task human EEG using the Grassberger-Procaccia method. AB - A method developed by Grassberger and Procaccia allows estimation of the dimensional complexity of the state-space attractor of a time series. Saturation of dimensional-complexity estimates with increasing values of embedding dimension is considered a strong indication that the time series is governed by deterministic chaos. The present investigation employed the Grassberger-Procaccia method to estimate EEG dimensional complexity in a multi-subject, factorial experiment. Twelve subjects were tested under two no-task conditions (eyes closed and open), with the block of two conditions being repeated four times. EEG was recorded from the nineteen 10-20 loci. Dimensional complexity declined across Blocks 1-3 and then leveled off, and was higher in the eyes-open than in the eyes closed condition. Condition also interacted with locus in that the increase in dimensional complexity associated with opening the eyes was greater over occipital loci. Comparison with the results of Fourier analysis indicated that a similar but not identical pattern of effects was obtained for alpha (8-12 Hz) power. Further, across the entire data set, if alpha power exceeded a value of about 70 microV2, dimensional complexity was uniformly low, a finding in concert with previous results indicating that the eyes-closed, occipital alpha rhythm possibly represents deterministic chaos of relatively low dimension. PMID- 1635961 TI - Effects of eating on vection-induced motion sickness, cardiac vagal tone, and gastric myoelectric activity. AB - This study investigated the effect of food ingestion on motion sickness severity and its physiological mechanisms. Forty-six fasted subjects were assigned either to a meal group or to a no-meal group. Electrogastrographic (EGG) indices (normal 3 cpm activity and abnormal 4-9 cpm tachyarrhythmia) and respiratory sinus arrhythmia (RSA) were measured before and after a meal and during a subsequent exposure to a rotating drum in which illusory self-motion was induced. The results indicated that food intake enhanced cardiac parasympathetic tone (RSA) and increased gastric 3 cpm activity. Postprandial effects on motion sickness severity remain equivocal due to group differences in RSA baseline levels. During drum rotation, dysrhythmic activity of the stomach (tachyarrhythmia) and vagal withdrawal were observed. Furthermore, high levels of vagal tone prior to drum rotation predicted a low incidence of motion sickness symptoms, and were associated positively with gastric 3 cpm activity and negatively with tachyarrhythmia. These data suggest that enhanced levels of parasympathetic activity can alleviate motion sickness symptoms by suppressing, in part, its dysrhythmic gastric underpinnings. PMID- 1635962 TI - Event-related potentials elicited by deviant endings to melodies. AB - Event-related potentials were recorded from scalp electrodes while subjects listened to well-known melodies. The melodies ended either with the expected note or with a different note. This design was a nonlinguistic analogue of the design used by Kutas and Hillyard (1980b), who first reported that anomalous terminal words in sentences elicited N400 potentials. However, Besson and Macar (1987) reported that deviant terminal notes in melodies did not elicit N400 potentials. In the present study, additional time was allowed for expectations to develop for the terminal note. Deviant terminal notes did not elicit N400s. In both studies, however, the deviant notes elicited P300-like waves. This outcome raised the possibility that N400 might have been masked by the positive potential. In a second condition in which P300 amplitude was minimized, N400s were again not evident. These results thus illustrate two additional situations in which nonlinguistic stimuli that deviated from a sequential pattern failed to elicit N400 potentials. PMID- 1635963 TI - Electrodermal lability: individual differences affecting perceptual speed and vigilance performance in 9 to 16 year-old children. AB - Studies on adults have suggested that a deterioration in performance (within session vigilance decrement) on a continuous performance task may be related to individual differences in baseline levels of electrodermal activity (electrodermal lability). This study investigated this relationship in 153 children, aged 9-16 years. A significant vigilance decrement was observed, as indicated by average decreases in perceptual sensitivity (d') over an 11.5-min time period. Although electrodermal labiles were overall more perceptually sensitive than electrodermal stabiles, results did not support the premise that the performance of stabiles decreases over time more than that of labiles. Performance on other cognitive tasks, involving tests of perceptual speed ability, did not appear to be highly related to vigilance performance. However labiles were not only better able to sustain their attention, but also performed better and faster on these cognitive tasks. PMID- 1635964 TI - A comparison between two methods for assessing heartbeat perception. AB - In this study two methods assessing heartbeat perception ability were compared. Subjects (N = 64) completed Schandry's (1981) mental tracking task and Stormer's (1988) heartbeat discrimination procedure (based on Whitehead, Drescher, Heiman, & Blackwell, 1977). In addition, subjects were tested on their ability to estimate the duration of time intervals. A high degree of correspondence was found between the two heartbeat perception tasks for the extreme groups of very good and very poor perceivers, but a low degree of correspondence emerged for the middle range of performance (overall r = .59, p less than .001). Time estimation did not correlate significantly with either heartbeat detection procedure. Blood pressure measurements taken after the Schandry task and between Stormer test blocks showed that blood pressure amplitude was elevated among good perceivers on both heartbeat detection tasks. PMID- 1635965 TI - Beat-by-beat cardiac responses in normals and schizophrenics to events varying in conditional probability. AB - Anticipatory cardiac deceleration and poststimulus acceleration were studied in schizophrenic inpatients and controls during performance of a counting task. Reduced cardiac responding has been reported for schizophrenic patients for paradigms using relatively long intertrial intervals. During a relatively fast rate of stimulus presentation (3-s interstimulus interval), changes in cardiac interbeat interval were measured in 20 inpatient male chronic schizophrenics and 18 control volunteers. Subjects counted an infrequent tone which was always followed by at least one frequent tone. Control subjects showed significant anticipatory cardiac deceleration preceding the unpredictable tones, whereas patients did not show a differential cardiac deceleration. Control subjects showed poststimulus acceleration that was inversely proportional to the conditional probability of events, whereas patients exhibited greatly reduced poststimulus acceleration; patterns for both groups resembled findings previously observed for event-related potential and pupillary dilation data. Analysis of cardiac cycle time indicated significant variation in primary bradycardia associated with the delay between stimuli and immediately preceding R-waves in controls (replicating Lacey & Lacey, 1980), with only an immediate bradycardia at stimulus reception for patients regardless of cardiac cycle time. The data reinforce the notion that the manner in which information is used by schizophrenics, as reflected by cardiac responsivity, differs both quantitatively and qualitatively from that of controls. PMID- 1635966 TI - Pregnancy alters blood pressure responses to psychological and physical challenge. AB - The purpose of the study was to evaluate the effect of the substantial changes in female reproductive hormones that occur during normal pregnancy on cardiovascular responses to psychological and physical challenges. Twenty-one healthy normotensive women performed serial subtraction, mirror image tracing, and isometric handgrip exercise tasks prior to pregnancy and again during the second trimester of pregnancy. A control group of 34 healthy women who did not intend to become pregnant and were nonpregnant were also tested in the same protocol twice, 6-10 months apart. Results showed that the pregnant women exhibited a reduced diastolic blood pressure response to all three tasks, relative to their pre pregnancy levels, whereas nonpregnant controls did not change in their diastolic blood pressure response across time. These results are consistent with the hypothesis that elevations in female reproductive hormones diminish blood pressure responses during challenge because of dampened sympathetic nervous system activity. PMID- 1635967 TI - A major effect of recording site on measurement of electrodermal activity. AB - Although the medial phalanx has been recommended as the preferred site for recording skin conductance activity, a review of articles published in Psychophysiology indicates that a large minority (34%) of studies employ the distal phalanx. Informal observations also suggest that the distal site may be more reactive than the medial site. This study formally tests this observation by recording skin conductance from both medial and distal phalanges. Twenty-four right-handed subjects (12 male, 12 female) were exposed to a series of 10 orienting and defensive stimuli. Electrodes were placed on the fore and middle fingers of each hand, with distal sites used on one hand and medial sites on the other for each subject. Skin conductance amplitudes were 3.5 times larger at distal than medial sites (p less than .002), while skin conductance levels were 2.08 times larger at distal sites (p less than .0005). A significant Site X Stimulus interaction (p less than .025) indicated that the distal site was more sensitive to habituation over trials and to increases in skin conductance amplitudes with increasing stimulus intensity than the medial site. On the basis of these findings it is recommended that distal sites be used in preference to medial sites in the recording of skin conductance activity. PMID- 1635968 TI - Dengue activity in Puerto Rico, 1990. AB - Reported dengue activity in Puerto Rico (PR) increased in 1990 for the fourth consecutive year. The Community Hygiene Division of the PR Health Department received 9,540 reports of suspected dengue cases. Of the blood samples obtained from 7,660 patients, 1,911 were confirmed as dengue infection by laboratory tests at the Dengue Branch, San Juan Laboratories, Centers for Disease Control. Dengue 2 (DEN-2) continued to be the most frequently isolated serotype among all confirmed cases, hospitalized patients, and the confirmed cases with hemorrhagic manifestations. Disease was reported throughout the island and during all months, but activity, as in previous years, was lowest from April through July, and highest from September to November. The highest rates of laboratory-confirmed illness occurred in towns on the south coast and in the central mountains, with only one or two circulating virus serotypes (DEN-2 in the south; DEN-2 and DEN-4 in the central mountains). Although cases were confirmed in infants and octogenarians, the majority of laboratory-confirmed cases (1,293, 68%), and the highest attack rates (0.70/1000), were reported in persons younger than 30. Of patients with confirmed cases, 289 (15%) were hospitalized, and 438 (23%) reported at least one hemorrhagic manifestation. One presumptive dengue case with fatal outcome was reported in 1990 in a 17-year-old woman in whom a febrile illness, seizures, and coma developed; she died after cardiorespiratory arrest. Recent dengue infection in this individual was serologically documented, but no virus was isolated. PMID- 1635969 TI - Glycation of blood proteins during pregnancy and lactation in the rat. AB - Non-enzymatic glycation of blood proteins is a time and concentration dependent process and has been used clinically to monitor carbohydrate metabolism during human pregnancy. Since gestation in rats is of much shorter duration than in humans (3 weeks vs 9 mos) the question was raised whether similar differences in glycated proteins could be observed. Therefore, levels of glucose, glycated hemoglobin and fructosamine were measured during normal pregnancy and lactation in rats. Glucose levels during late pregnancy were significantly lower than in non pregnant and early pregnant rats. During lactation glucose levels return to normal. Glycated hemoglobin paralleled glucose decrease during late pregnancy and increased during lactation. Fructosamine followed a similar pattern. Therefore glycated hemoglobin and fructosamine appear to be reliable indicators of glucose status during gestation and lactation similar to humans and may have value as predictors of gestational diabetes mellitus once a suitable rat model is developed. PMID- 1635970 TI - Prelude activities in the synthesis of tissue-specific secretory protein products. AB - In studying the process of protein synthesis of a silk-producing organism we have found that several macromolecules must be synthesized in order for the process to occur. Through time course studies, we have found that small RNAs may play a paramount role in directing the finely orchestrated process. Alanine tRNA, U1 snRNA, and 5S RNA have been identified through Northern blotting as molecules timely and tissue-specific synthesized and upgraded as a prelude activity for the silk being produced. PMID- 1635971 TI - Extraction and purification of a catalase from Candida albicans. AB - Candida albicans yeast cells H317 were grown to mid-log phase, mechanically disrupted and the resulting crude extract clarified by centrifugation. This catalase rich fraction (1.26 x 10(-4) units/ml) was fractionated by liquid phase isoelectric focusing in a pH gradient ranging from 3 to 10 using the Rotofor Isoelectric Focusing Preparative Cell. After isoelectric separation, fractions containing catalase activity were focused between pH 6.7 and 9.3. Active fractions were pooled and re-focused. After the second fractionation, catalase activity increased to 1.52 x 10(-2) units/ml and was restricted to fractions ranging from pH 7.6 to 8.8. To this point a 121 fold purification was achieved. Native polyacrylamide gel electrophoresis analysis of active fractions revealed a band migrating between 272,000 and 132,000 daltons which showed catalase activity. Purification of C. albicans catalase will allow us to evaluate its potential role in protecting this opportunistic pathogen from products of the oxidative burst. Antibodies generated against the catalase provide means for the evaluation of neutralizing fungal defenses against products of the oxidative burst during phagocytosis. PMID- 1635972 TI - [HIV infection and AIDS: neuropsychiatric and neuropsychological aspects]. AB - The progressive confirmation of the neurotropic character of HIV, in juxtaposition to the recognition of AIDS dementia complex as an important central nervous system clinical manifestation, have engendered a greater interest in this phenomena. Consequently, a more precise description of the behavioral and mental aspects of this infection have evolved. This article has two purposes, to discuss the AIDS dementia complex concept and secondly, to review the neuropsychiatric and neuropsychological aspects of infection by HIV and AIDS, as it pertains to adult patients. PMID- 1635973 TI - Faculty and dental auxiliaries exchange program between the University of Granada and the University of Puerto Rico dental schools. PMID- 1635974 TI - [Medical Center of Puerto rico. Problems and solutions]. PMID- 1635975 TI - [Considerations on interdisciplinarity: theory and practice]. AB - The curricular content of undergraduate programs in the health sciences should integrate, in a logical and coherent manner, competencies in general education as well as professional and interdisciplinary competencies. Among the principal obstacles for integration discussed are inflexibility of administrative and accreditation policies and lack of an interdisciplinary vision in curriculum development. This article examines the need to prepare a graduate with competencies to attend patient/client as a holistic human being, thus requiring to make use of psychological, ethical, legal & philosophical knowledge as well as concepts, skill and attitudes of the profession. The program of Bachelor in Health Sciences of the College of Health Related Professions is presented as one of an interdisciplinary nature, in which 23 percent of the total credits are general education courses, 49 percent are professional courses, 17 percent are interdisciplinary courses and 11 percent are elective courses. PMID- 1635976 TI - The evolution of delayed dispersal in cooperative breeders. AB - Why do the young of cooperative breeders--species in which more than two individuals help raise offspring at a single nest--delay dispersal and live in groups? Answering this deceptively simple question involves examining the costs and benefits of three alternative strategies: (1) dispersal and attempting to breed, (2) dispersal and floating, and (3) delayed dispersal and helping. If, all other things being equal, the fitness of individuals that delay dispersal is greater than the fitness of individuals that disperse and breed on their own, intrinsic benefits are paramount to the current maintenance of delayed dispersal. Intrinsic benefits are directly due to living with others and may include enhanced foraging efficiency and reduced susceptibility to predation. However, if individuals that disperse and attempt to breed in high-quality habitat achieve the highest fitness, extrinsic constraints on the ability of offspring to obtain such high-quality breeding opportunities force offspring to either delay dispersal or float. The relevant constraint to independent reproduction has frequently been termed habitat saturation. This concept, of itself, fails to explain the evolution of delayed dispersal. Instead, we propose the delayed dispersal threshold model as a guide for organizing and evaluating the ecological factors potentially responsible for this phenomenon. We identify five parameters critical to the probability of delayed dispersal: relative population density, the fitness differential between early dispersal/breeding and delayed dispersal, the observed or hypothetical fitness of floaters, the distribution of territory quality, and spatiotemporal environmental variability. A key conclusion from the model is that no one factor by itself causes delayed dispersal and cooperative breeding. However, a difference in the dispersal patterns between two closely related species or populations (or between individuals in the same population in different years) may be attributable to one or a small set of factors. Much remains to be done to pinpoint the relative importance of different ecological factors in promoting delayed dispersal. This is underscored by our current inability to explain satisfactorily several patterns including the relative significance of floating, geographic biases in the incidence of cooperative breeding, sexual asymmetries in delayed dispersal, the relationship between delayed dispersal leading to helping behavior and cooperative polygamy, and the rarity of the co-occurrence of helpers and floaters within the same population. Advances in this field remain to be made along several fronts.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1635977 TI - Is there teaching in nonhuman animals? AB - We derive a simple operational definition of teaching that distinguishes it from other forms of social learning where there is no active participation of instructors, and then discuss the constituent parts of the definition in detail. From a functional perspective, it is argued that the instructor's sensitivity to the pupil's changing skills or knowledge, and the instructor's ability to attribute mental states to others, are not necessary conditions of teaching in nonhuman animals, as assumed by previous work, because guided instruction without these prerequisites could still be favored by natural selection. A number of cases of social interaction in several orders of mammals and birds that have been interpreted as evidence of teaching are then reviewed. These cases fall into two categories: situations where offspring are provided with opportunities to practice skills ("opportunity teaching"), and instances where the behavior of young is either encouraged or punished by adults ("coaching"). Although certain taxonomic orders appear to use one form of teaching more often than the other, this may have more to do with the quality of the current data set than with inherent species-specific constraints. We suggest several directions for future research on teaching in nonhuman animals that will lead to a more thorough understanding of this poorly documented phenomenon. We argue throughout that adherence to conventional, narrow definitions of teaching, generally derived from observations of human adult-infant interactions, has caused many related but simpler phenomena in other species to go unstudied or unrecorded, and severely limits further exploration of this topic. PMID- 1635978 TI - Haldane's Causes of Evolution after 60 years. PMID- 1635979 TI - [Imaging of the liver segments by ultrasound. A practical approach]. AB - Segmentation of the liver according to Couinaud is the anatomical basis for hepatic surgery. Based upon the dichotomic branching of the portal vein and its ramifications the liver is divided into lobes (right, left and caudate): 4 double segments (DS) (right lobe: anterior and posterior DS; left lobe: medial and lateral DS); and 8 segments (S): caudate lobe (S I); lateral DS (S II and S III); medial DS (S IV); anterior DS (S VIII and S V); posterior DS (S VII and S VI). This three-dimensional concept can also be used in US using hepatic veins, the portal vein and its branches, hepatic fissures and ligaments as landmarks. The localization and extent of a tumor and its relationship to the vasculature of the liver can thus be determined and the surgical management of such patients can be improved. The exact definition of each segment of the liver by US is shown and the preoperative localizations in several cases of surgically confirmed liver tumors are presented. PMID- 1635980 TI - [Sonography of focal liver changes. Practical indications for differential diagnosis]. AB - This article reviews the sonomorphologic features of malignant and benign focal liver lesions. Common methodological sources of diagnostic errors, features which benign and malignant findings have in common as well as the limitations of the method and further diagnostic procedures are described. PMID- 1635981 TI - [Portal computed tomography. Methodology and indications]. AB - CT arterioportography (CTAP) requires intra-arterial contrast material via the superior mesenteric (splenic) artery. Malignant hepatic tumors are characterized by arterial vascularization and only minimal portal blood supply. Portal contrast therefore reveals small tumors with a high sensitivity of 68-87%. Sensitivity is higher in metastatic tumors than in hepatocellular carcinomas. CTAP is the method of choice for evaluation of the number, size and location of hepatic tumors prior to surgical intervention. If the findings are unclear, additional magnetic resonance imaging and sonography during the operation are useful. PMID- 1635982 TI - [Status and development of new clinical contrast media for MR diagnosis of liver diseases]. AB - MR contrast agents are developed for pharmaceutical manipulation of tissue signal intensities. Today it is widely recognized that MR contrast agents will play an increasingly important role in MR imaging of the liver. Contrast-enhanced MR imaging allows to obtain simultaneously dynamic physiologic information and high anatomic detail. Up to now three major classes of MR contrast agents are available for clinical MR-imaging of the liver. These include paramagnetic perfusion agents, hepatobiliary agents, and super-paramagnetic RES-specific iron oxide particles. A fourth class of contrast agents now in use for animal experiments includes ultra-small super-paramagnetic particles which can be targeted to extra-reticuloendothelial structures such as asialoglycoprotein receptors of hepatocytes. In this article, we review recent advances in the development of MR contrast media and the clinical status of contrast-enhanced MR imaging of the liver. PMID- 1635983 TI - [The value of magnetic resonance tomography in the detection and differential diagnosis of focal liver lesions]. AB - Magnetic resonance imaging (MRI) of the liver has made considerable progress due to improvements in the examination technique. Sensitivity for the detection of focal liver lesions is higher for MRI than for CT. In the differential diagnosis of liver tumors MRI is remarkably accurate. This is particularly true for hemangiomas, liver cell carcinomas and focal nodular hyperplasias. From a clinical view point differentiation between hemangiomas and metastases is of utmost importance. Future improvements in MR diagnosis of liver diseases are expected due to fast imaging techniques and liver-specific contrast agents. PMID- 1635984 TI - [Radiologic diagnosis before and after liver transplantation]. AB - The main function of imaging procedures before liver transplantation is the exclusion of factors that may either constitute contraindications to surgery or necessitate a modification of the operation technique. Ultrasound and MRI are the modalities best suited for this purpose. After transplantation, imaging procedures are required mainly for diagnosis of and differentiation, in particular, between vascular and biliary complications, rejection, and infection, since these postoperative complications very often cannot be reliably differentiated on the basis of clinical and laboratory parameters alone. As vascular disturbances can vary widely in their presentation and can mimic other complications, duplex Doppler sonography plays a dominant role in clarification of the perfusion status of the graft. If infection is suspected, ultrasound generally has to be supplemented by other imaging procedures such as CT or MRI; if these techniques reveal suggestive lesions, a fine-needle aspiration is mandatory in most cases. Invasive procedures such as angiography or PTC are now applied only in selected cases, especially if an intervention is contemplated. Rejection cannot be reliably diagnosed by any of the imaging techniques and still requires biopsy. PMID- 1635985 TI - [MRT of the hand and wrist of sport climbers. Imaging of injuries and consequences of stress overload]. AB - The hands and wrists of 20 top-level rock climbers with sports injuries and overstress abnormalities were compared with the hands and wrists of 10 normal volunteers. They were all studied with MR imaging at 1.5 T. The imaging protocol included spin-echo and gradient-echo sequences with 1- to 5-mm-thick contiguous slices in the axial, coronal and/or sagittal planes, depending on the location and nature of the suspected injury. Typical hand and wrist lesions depicted with MRI in climbers consisted of anular ligament tears, lesions of the flexor tendons, tenosynovitis, ganglion cysts, joint effusion and functional carpal tunnel syndrome. The MRI findings on these abnormalities were compared to normal findings and those with ultrasound and plain films. In addition, hypertrophic changes in the muscles, tendons, ligaments, and bones of top-level rock climbers were assessed morphometrically. MRI proved to be the superior imaging modality in the diagnosis of sports injuries and overstress abnormalities of the hand and wrist in rock-climbing athletes. PMID- 1635986 TI - [Product of the month: a bibliographic database with optional formatting capability]. AB - The function and usage of the software package "Endnote Plus" for the Apple Macintosh are described. Its advantages in fulfilling different requirements for the citation style and the sort order of reference lists are emphasized. PMID- 1635987 TI - [Acute abdominal pain with a massively dilated intestinal segment. Cecal volvulus]. PMID- 1635988 TI - [Magician and apprentice: the confrontation between Karl Kraus and Sigmund Freud]. PMID- 1635989 TI - [Identity and the self. The importance of recent developmental research for the psychoanalytic theory of the self]. AB - Recent findings from research on human development have implications for the psychoanalytic concepts of self and identity. The emerging feeling of selfhood appears to be the precipitate of finely tuned interactive regulations involving mother and child. Similarly, early mirroring processes are shown to have a fundamental significance for the experimental structure of self and identity. The author discusses the new meanings acquired by the identity concept as a result of these investigations. He describes the elementary psychic structures of identity as well as the subordinate regulatory function of the sense of identity. PMID- 1635990 TI - [Debit and credit. Menopause between illusion and reality]. AB - Middle-aged women in patriarchial societies are still widely considered as deficient and damaged and therefore can easily become objects of medical attention. The authors seek the reasons for this in fact that the different changes of male and female potency in the 45 to 55 age-group provoke defense mechanisms. These are meant to ensure the intactness of the male--who then is supposedly in his 'best age'--for the sake of both men and women. Apart from this, psychoanalytical theories--like the one of the "depressive position", held by Melanie Klein--confirm the prejudice that a woman going through the change of life is damaged, and thus has to mourn the "desease" of menopause. PMID- 1635991 TI - [Interpretation between determinism and hermeneutics. A new approach]. AB - There are two traditional views of psychoanalytic interpretation. One takes its bearings from Freud and regards the present condition of the subject as determined by his/her real past. The objective is then to uncover the "real" history. The other may be termed hermeneutic/creative and has its origins in authors such as C.G. Jung and Paul Ricoeur. It looks upon interpretation as a process of conferring subsequent significance on a fragmentary past devoid of meaning. In an attempt to break away from this rigid dualism, the author describes interpretation in the analysis context as a method of deconstruction with the aim of creating scope for new constructions that are the work of the person undergoing analysis. In the light of this approach interpretation reveals itself as an expression of the unity of constraint (determinism) and freedom (hermeneutics). PMID- 1635992 TI - [The working alliance is St. Stephan's cathedral. Epistemological considerations of the Heinrich Deserno lecture, "Analysis and the working alliance" (1990)]. AB - With the term "working alliance", as it was discussed by R.R. Greenson in noted publications, an understanding of work was introduced that corresponds with the dominant contemporary idea of work as a purely instrumental and technical process which is alien to the original "spirit" of Freudian Analysis. The author shows that psychological work, which in analysis is carried out cooperatively by analyst and analysand, needs transference to be successful, a transference with the help of which the analysand is able to discuss and specify his unconscious psychological conflicts. In Greenson's understanding the working alliance- supposedly neurosis-free--appeals to the rational part of the ego and introduces a normative understanding of reality. The transference relationship, by contrast, gives room to those psychic forces which refuse to obey the authority of the ego and its tendencies to conventionalize and suppress unconscious material. PMID- 1635993 TI - [The working alliance and psychoanalysis in theory and practice]. AB - The author points out a remarkable discrepancy between the concept of work in the practice of psychoanalysis, especially in the concept of the working alliance (Greenson), and the concept of work included in the dreamwork. PMID- 1635994 TI - ["The very wise Heloise". On dependency and resistance of the female in relation to actual male dominance and the magic power of its representation]. AB - Psychoanalytical theory of femininity starts from the assumption that specific patterns of identification can be traced back historically to ancient traditions which frequently remain unconscious to those concerned. In the 12th century, the abbess Heloise advocated ideals which on the one hand questioned the medieval image of woman, while on the other hand she sought to be in accordance with the socially domineering male (Abaelard) who represented the intellectual life. The correspondence between Heloise and Abaelard reveals paradigmatically Heloise's conflict between rebellion and resignation, between the striving for autonomy and regression, which is resolved in some form of female narcissism. PMID- 1635995 TI - [The interpersonal alliance as the principle of psychoanalytic therapy]. AB - The classical opinion encountered in psychoanalytic psychotherapy is that the main curative agent is language, i.e. the information proffered by the analysand and the interpretations of the analyst. Over and against this view the author draws attention to the non-verbal structures in the twosome relationship between analysand and therapist. Essential elements of this working alliance, he suggests, operate via non-verbal behaviour. Hence this behaviour needs to be systematically observed and evaluated. His conclusion is that it requires the consideration of non-verbalized fantasies and affects for the therapeutic relationship to develop into a "good relationship". PMID- 1635997 TI - [The self and its fate. A "archeological" study of psychoanalytic avant garde (II)]. PMID- 1635996 TI - [Insight in psychotic disorders]. PMID- 1635998 TI - [A body of one's own. Sexual development and physical female development in the mother-child relationship]. AB - Prevalent psychoanalytic opinion has it that (sexually) femaleness is marked by a severe deficiency. Accordingly it is widely held that the acknowledgement of female sexuality is primarily a matter for fathers rather than mothers. The author takes a different stance, insisting on the opportunities inherent in the mother-daughter relationship to the extent that it both permits and encourages pleasurable self-examination and acceptance of the body on the part of the growing girl. In the therapeutic connection, the author calls for a form of remedial socialisation to fill the specific lacunae that have developed around female sexuality. PMID- 1635999 TI - [From the sense organ of the skin to the imaginary envelope of the self. On Didier Anzieu's "The skin self"]. PMID- 1636000 TI - [Was Freud's confrontation with psychiatry only an episode or experience, which formed his further scientific development?]. PMID- 1636001 TI - The Women's Policy Unit moves into its second year: women on the agenda. PMID- 1636002 TI - Aged care funding. PMID- 1636003 TI - Brisbane Youth Service: an innovative health programme. PMID- 1636004 TI - Caring for the aged--but who cares for the carers? PMID- 1636005 TI - Remote area nursing--needs must be recognised. PMID- 1636006 TI - Lexical mediation between sight and sound in speechreading. AB - In two experiments, we investigated whether simultaneous speech reading can influence the detection of speech in envelope-matched noise. Subjects attempted to detect the presence of a disyllabic utterance in noise while watching a speaker articulate a matching or a non-matching utterance. Speech detection was not facilitated by an audio-visual match, which suggests that listeners relied on low-level auditory cues whose perception was immune to cross-modal top-down influences. However, when the stimuli were words (Experiment 1), there was a (predicted) relative shift in bias, suggesting that the masking noise itself was perceived as more speechlike when its envelope corresponded to the visual information. This bias shift was absent, however, with non-word materials (Experiment 2). These results, which resemble earlier findings obtained with orthographic visual input, indicate that the mapping from sight to sound is lexically mediated even when, as in the case of the articulatory-phonetic correspondence, the cross-modal relationship is non-arbitrary. PMID- 1636007 TI - Do abrupt-onset peripheral cues attract attention automatically? AB - The proportion of peripheral cues that predicted at which of two locations a discrimination target would occur was manipulated in three experiments. Near cues occurred adjacent to the target and far cues occurred adjacent to the other location. In Experiment 1, near and far cues were presented in separate blocks so each predicted target location. Both types of cue produced benefit relative to a neutral baseline. In Experiment 2 expectancy for near versus far cues was manipulated. In one group, 80% of the peripheral cues were near; in another, only 20% were near; in a third, near and far cues occurred randomly. Near cures always produced benefit. Far cues produced benefit when they were expected, had no effect in the random group, and sometimes produced cost when they were unexpected. Experiment 3 repeated the near-expected and far-expected conditions, but target duration was shortened to 50 msec. A similar pattern emerged, except that near cues produced less benefit at longer SOAs when they were unexpected. The data suggest that peripheral, abrupt-onset cues may produce benefit via an automatic process, but that such a process is more like location priming than the capture of attention. Expectancy determines whether and where attentional resources will be allocated in response to the cue. PMID- 1636008 TI - Pragmatic schemas and the selection task: to reason or not to reason. AB - Cheng and Holyoak (1985) have proposed that people possess classes of linguistically based schemas that have an internal structure that is determined by pragmatic considerations. They found that when permission schemas ("If you want to do P, then you must do Q") are used in the selection task, the success rate is much superior to what is usually observed. According to Cheng and Holyoak, this is due to the fact that the permission schema is defined by a set of production rules that give the same answers to problems of conditional inference as those of formal logic. In order to test this hypothesis specifically, 160 university students were given one of two tests. The first contained two sets of inferential reasoning tasks, one using a permission schema, the second using a relation of multiple causality. The second test employed the same two conditional relations, but in an appropriate context. The results indicated that subjects did better on the reasoning task with the schema of multiple causality when presented in context, but, as predicted, their performance was much worse on the inferential reasoning task with the permission schema, which generated a higher proportion of logically incorrect responses. These results suggest that contrary to what has been affirmed, permission schemas might not have a logical structure that is equivalent to conditional logic. A second experiment examined selection task performance using the same two relations in context. Performance on the permission schema was superior to that found with the relation of multiple causality. This confirmed previous results indicating that permission schemas do improve selection task performance, but also suggests that this effect is not related to understanding of conditional reasoning. PMID- 1636009 TI - Mobilization of cognitive resources and the generation effect. AB - The generation effect refers to the memory advantage of words that have been generated rather than read. Such a read-generate comparison confounds qualitative task differences and raises methodological problems. A revised methodology is proposed circumventing these problems in that the encoding task is held constant and all stimuli have to be generated, but the degree of generativeness (i.e. the amount of cueing) is varied. In Experiment 1, 1, the (refined version of the) generation effect is demonstrated in a within-subjects design; with increasing generation activity left to the subject, free recall performance increases. No effect is obtained for degree of target masking. The same finding is replicated and shown to be independent of self-paced study time when generative activity is manipulated between subjects (Experiment 2) or within subjects (Experiment 3). As all learning trials involve generation, encoding time is controlled statistically, and free recall is used as a measure of memory, this refined generation effect cannot be explained as an artifact of selective attention or elaboration. Rather, generative activity seems to increase the mobilization of cognitive resources. This motivational account is supported by Experiment 4 showing an enhanced generation effect for positive mood. PMID- 1636010 TI - Phonology, working memory, and foreign-language learning. AB - Three tasks were used to predict English learning by Finnish children over a three-year period. In the pseudoword repetition task the pupils had to repeat aloud tape-recorded pseudowords sounding like Finnish or English. In the pseudoword copying task the pupils saw strings of letters resembling Finnish or English words and copied them when they had disappeared from view. When comparing syntactic-semantic structures, the pupils had to find the syntactically matching pairs from two sets of Finnish sentences. Repetition and copying accuracy and the ability to compare syntactic-semantic structures predicted English learning. Intercorrelations between test scores and English and mathematics grades suggest that repetition and copying accuracy were specifically related to language learning. It is concluded that the ability to represent unfamiliar phonological material in working memory underlies the acquisition of new vocabulary items in foreign-language learning. PMID- 1636011 TI - Incidentalomas: problems of diagnostic assessment. PMID- 1636012 TI - Adrenal glands: metastases, lymphomas, infections and cysts. PMID- 1636013 TI - Unusual and coincidental presentation of metastatic pheochromocytoma. Report of three cases. PMID- 1636014 TI - Diagnostic imaging of adrenal diseases. PMID- 1636015 TI - Radiologic imaging of hyperadrenocorticism syndromes. PMID- 1636016 TI - Adrenocortical scintigraphy. PMID- 1636017 TI - Radiocholesterol scintigraphy in Cushing's syndrome. PMID- 1636018 TI - Primary aldosteronism and hyperandrogenism. PMID- 1636019 TI - Diagnostic imaging of neuroblastoma. PMID- 1636020 TI - Effect of interaction between gentamicin and pyridoxal-5-phosphate on functional and metabolic parameters in kidneys of female Sprague-Dawley rats. AB - Daily intraperitoneal (i.p.) injection of genatmicin at a dose of 70 mg/kg for 11 days produced nephrotoxicity in female Sprague-Dawley rats as evidenced by increased excretion of urinary protein and trypsin inhibitory activity as well as rise in renal individual class and total phospholipid. The observed proteinuria was associated with a significant twofold fall in creatinine clearance and histopathological changes, including the presence of hyaline casts and flattened epithelial cells within the lumen of proximal convoluted tubules. Although pyridoxal-5-phosphate (50 mg/kg) administered i.p. did not significantly alter creatinine clearance, histopathology, proteinuria, and urinary trypsin inhibitory activity, an increase in individual class and total phospholipid was noted in kidney. In rats simultaneously administered gentamicin and pyridoxal-5-phosphate, the observed fall in renal gentamicin content was associated with a return of individual class and total phospholipid to control values. However, the decline in creatinine clearance, enhanced proteinuria, and increase in urinary trypsin inhibitory activity in the simultaneous-treated group was similar or greater than that seen in the gentamicin-only injected rats. Morphological examination of simultaneous-treated rats revealed extensive alterations in proximal tubules including numerous mitotic figures, large vesicular nucleii, and prominent nucleoli in epithelial cells as well as hyaline casts within the lumen. Our data combined with results of previous studies suggest that sex and type of rat strain are important factors in aminoglycoside-induced nephrotoxicity. It is evident that a specific concentration of pyridoxal-5-phosphate may be necessary to provide protection against all manifestations of aminoglycoside-induced renal damage. PMID- 1636021 TI - Effect of captopril on urinary excretion of renin and angiotensinogen in aminonucleoside nephrosis. AB - Puromycin aminonucleoside (PAN)-nephrotic rats show high plasma renin, low plasma angiotensinogen (Angt), and increased urinary excretion of renin and Angt. In this work, we studied the effect of captopril on urinary excretion of total protein, renin, and Angt for 25 days after PAN injection. Captopril had no effect on total protein urinary excretion; however, captopril did enhance the urinary excretion of renin and did decrease the urinary excretion of Angt. This seems to be due to the fact that captopril magnifies the increase in renin and the decrease in Angt in the plasma of PAN-nephrotic rats. PMID- 1636022 TI - Clinical profile and factors affecting mortality in acute renal failure. AB - The records of 110 patients with acute renal failure (ARF) admitted to the Department of Medicine of the Philippine General Hospital during a 5-year period (1983-1988) were reviewed. The objectives were to evaluate the clinical profile of ARF patients and to determine what factors influenced mortality. Infection significantly influenced the causation and prognosis of ARF. Fifteen patients died, for an overall mortality rate of 14%. Forty-six clinical variables were analyzed in order to identify factors correlated with mortality. Four variables significantly increased the risk of death from ARF: older age, hyperkalemia, oliguria, and presence of sepsis on admission. These characteristics define a subset of patients for whom more aggressive treatment of ARF is warranted. PMID- 1636023 TI - Glomerulotubular function in patients undergoing moderate surgical stress. AB - Glomerular function and renal tubular function assessed by measurements of creatinine clearance rates (CCR), lithium clearance rates (CLi, and N-acetyl-beta D-glucosaminidase (NAG) enzymuria were measured immediately prior to and within 24 h of operation (average operative time 150 min) in 16 patients undergoing a moderate surgical stress. Although serum creatinine concentrations and CCR were similar pre- and postsurgery at 105 +/- 21 and 108 +/- 21 mumol/L and 108 +/- 67 and 110 +/- 59 mL/min/100 kg body weight (mean +/- SD), respectively, both CLi and NAG were significantly increased following the surgical insult. CLi was increased from 19.7 +/- 6.1 to 31.7 +/- 16.7 mL/min/100 kg (p less than 0.01) and NAG from 71 +/- 58 to 164 +/- 10 U/mmol urinary creatinine (p less than 0.001). In addition, the absolute distal tubular reabsorption of sodium and water increased from 18.3 +/- 5.9 and 15.8 +/- 9.7 to 30.6 +/- 16.4 and 27.6 +/- 12.2 mL/min/100 kg body weight (both p less than 0.05), respectively. These results indicate early postoperative renal tubular dysfunction following a moderate surgical stress, undetected by conventional screening. PMID- 1636024 TI - Cyclosporin A abolishes renal reserve capacity. AB - Renal functional reserve (RFR) was investigated in a group of renal transplant recipients taking cyclosporin A (CyA) immunosuppressive therapy. Nine patients received a 93 g oral protein load containing 5983 mg of glycine. GFR and ERPF were measured using isotope infusions of 51Cr EDTA and 125I OIH, respectively, before and for 3 h after the meal. Patients studied demonstrated a wide range of baseline GFRs (20.9-89.5 mL/min, mean 50.09 mL/min). However, few patients demonstrated an individual RFR, regardless of original level of function. Overall, no significant change in either GFR or ERPF was demonstrated after the protein stimulus. CyA is known to alter intrarenal prostanoid synthesis in favor of vasoconstriction and RFR is thought to be mediated by prostanoids. Therefore a mechanism for the absence of RFR in patients receiving CyA therapy is suggested. PMID- 1636025 TI - Management of acute renal failure in the critically ill with continuous venovenous hemodiafiltration. AB - Continuous venovenous hemodiafiltration (CVVHD) has been increasingly utilized for renal replacement therapy in the critically ill. We report details of a prospective study of CVVHD in 12 critically ill patients (7 males, 5 females; mean age 60 years, range 30-72 years; Apache II score mean 27.4, range 21-35) with oligoanuric acute renal failure supported on CVVHD. Vascular access was obtained via double lumen subclavian or femoral cannulae. The mean pretreatment urea was 35.9 mM/L and the mean pretreatment creatinine was 559 microM/L. After 24 h of treatment on CVVHD these fell to a urea mean of 20.3 mM/L and a creatinine mean of 298 microM/L and remained stable at these values for the duration of CVVHD. The mean net ultrafiltrate volume was 551 mL/h, with a urea clearance mean of 26.6 mL/min and a creatinine clearance mean of 23.7 mL/min. There were no complications related to use of the blood pump module or extracorporeal circuit. Excellent hemodynamic stability, control of fluid and electrolyte balance, and azotaemia control were maintained while on CVVHD. Technique survival was 100%. Patient survival was 42%. We conclude that CVVHD is a safe, effective, and durable therapy for the treatment of acute renal failure in the critically ill and that it offers outstanding metabolic control and cardiovascular stability. PMID- 1636026 TI - Effects of suprofen on the isolated perfused rat kidney. AB - Although suprofen has been associated with the development of acute renal failure in greater than 100 subjects, the mechanism of damage remains unclear. The direct nephrotoxic effects of a single dose of 15 mg of suprofen were compared in the recirculating isolated rat kidney perfused with cell-free buffer with or without the addition of 5 mg/dL of uric acid. There were no significant differences in renal sodium excretion, oxygen consumption, or urinary flow rates in kidneys perfused with suprofen compared with the drug-free control groups. In contrast, a significant decline in glomerular filtration rate was found after the introduction of suprofen to the kidney perfused with uric acid; no changes were found with suprofen in the absence of uric acid. A significant decrease in the baseline excretion rate of uric acid was found in rats given suprofen, compared with drug-free controls. However, the fractional excretion of uric acid was unchanged between the groups over the experimental period. In summary, suprofen causes acute declines in renal function, most likely by directly altering the intrarenal distribution of uric acid. PMID- 1636027 TI - The diagnostic value of CT scan in acute renal cortical necrosis. AB - We report the characteristic CT scan findings of renal cortical necrosis in a patient of acute renal failure, which was confirmed on renal biopsy. CT scan is a useful, noninvasive investigative modality for an early diagnosis of renal cortical necrosis. PMID- 1636028 TI - Bladder involvement in systemic amyloidosis causing massive hemorrhage in hemodialysis. AB - We report a chronic hemodialyzed patient with bladder involvement of a secondary amyloidosis that presented as isolated hematuria evolving quickly to a massive hemorrhage and vesical rupture. We believe that this is the first report of bladder amyloidosis involvement in the course of hemodialysis. This knowledge may help in managing dialysis patients with hematuria. PMID- 1636029 TI - Technical advances in transjugular intrahepatic portosystemic shunts. AB - A transjugular intrahepatic portosystemic shunt (TIPS) can be created percutaneously with the Palmaz balloon-expandable stent. This article describes a transjugular-only approach with a 16-gauge needle. A functional and efficacious shunt can be achieved in most cases with stent diameters of 8-10 mm. Occasionally, a 12-mm-diameter shunt is necessary for effective variceal decompression. The procedure is considered successful when the portosystemic gradient is lowered to 12 mm Hg or less after stent placement. Hepatic vein stenosis in the shunt outflow can develop after the TIPs procedure. This complication has been treated successfully with additional stent placement. TIPS can undoubtedly be performed successfully and safely with a transjugular-only approach; however, the full impact of TIPS on the treatment of portal hypertension remains to be determined. PMID- 1636030 TI - Stridor and upper airway obstruction in infants and children. AB - Upper airway obstruction in infants and children is a common and distressing problem because of the relatively narrow diameter of the airway in early life. Although ultrasound, computed tomography, and magnetic resonance imaging have become increasingly popular modalities for use in many pediatric diseases, plain radiography and fluoroscopy, with attention to technique, collimation, and patient position, continue to be the mainstays for the evaluation of stridor in children. An understanding of normal airway anatomy and air flow dynamics is necessary for this evaluation. This article presents the diagnostic features of conditions a radiologist may encounter in an infant or child with upper airway obstruction. Plain radiographic and fluoroscopic findings from over 100 cases of infants and children with this condition were reviewed to determine how frequently the specific diagnosis was confirmed with these studies. In the vast majority of cases, plain radiography and fluoroscopy suffice. PMID- 1636031 TI - Diseases of the trachea and main-stem bronchi: correlation of CT with pathologic findings. AB - This article presents the computed tomographic (CT) features of the most common abnormalities of the trachea and main-stem bronchi and correlates CT and pathologic findings. The abnormalities are classified into focal and diffuse. Focal disease tends to produce a decreased airway diameter, whereas diffuse diseases are divided into those that increase the airway diameter and those that decrease it. Conventional CT with 10-mm collimation was performed in 36 patients to assess their condition. Additional dynamic incremental thin-section (1.5-5.0 mm collimation) CT was performed in patients with focal abnormalities. Findings from conventional CT correlated closely with those from pathologic analysis of specimens from patients with diffuse disease, but dynamic thin-section scans are necessary for optimal assessment of focal abnormalities. CT demonstrates the location and extent of disease; helps characterize abnormal tissues; helps evaluate the thickness of the tracheal and bronchial walls; and helps determine the extent of extraluminal disease, including the presence of mediastinal extension and lymphadenopathy. PMID- 1636032 TI - Cardiac valve reconstruction and replacement: a brief review. AB - Surgical methods for improving the function of diseased cardiac valves are valve reconstruction (valvuloplasty) and valve replacement with mechanical prostheses, biologic prostheses, or homograft (donor) valves. Reconstruction is used primarily for incompetent mitral and tricuspid valves and addresses each part of the valve apparatus individually. Annuloplasty rings are often used to restore the size and shape of the valve orifice. Long-term anticoagulation therapy is not necessary. The designs of mechanical prostheses have evolved since the early caged-ball prostheses. Current models are noted for their durability. Patients who undergo implantation of these prostheses must also undergo long-term anticoagulation therapy. Biologic prostheses made from porcine valves or bovine pericardium are not as durable as their mechanical counterparts, but they do not require long-term anticoagulation therapy. Homografts are used in relatively few centers. They have good hemodynamics and do not necessitate long-term anticoagulation therapy. Radiologists should be familiar with the radiographic appearance of the various valve prostheses and annuloplasty rings and with the advantages and disadvantages of their use in cardiac valvular surgery. PMID- 1636033 TI - Cystic masses of the pancreas. AB - Although the pseudocyst is the most common cystic mass of the pancreas found at imaging studies, radiologists should be aware of the multiple disease processes that can manifest in a similar manner. This article reviews these other entities by category of the origin of the mass, including congenital, inflammatory, and neoplastic. Computed tomography, ultrasound, and magnetic resonance imaging studies are presented, and, although the considerable overlap of imaging features makes it generally impossible to render a specific diagnosis, combining the findings from these modalities is helpful in formulating a differential diagnosis. Because a cystic mass of the pancreas is not always a pseudocyst, percutaneous drainage should be followed by cytologic analysis of the aspirate. A biopsy of the wall of the cystic mass may also be necessary. PMID- 1636035 TI - Diagnosis of colon disease in the 1990s: radiologists should take a stand. PMID- 1636034 TI - Chondrosarcoma: MR imaging with pathologic correlation. AB - Magnetic resonance (MR) images of 21 surgically confirmed chondrosarcomas were retrospectively reviewed in conjunction with plain radiographs and computed tomographic scans and correlated with pathologic findings. The tumors appeared lobulated, and signal intensity, as analyzed visually (intermediate on T1 weighted, high on T2-weighted images), was similar for all lesions, regardless of pathologic type. Size of lesion was not an indicator of grade. The appearances of mesenchymal and dedifferentiated chondrosarcomas mimicked that of conventional chondrosarcoma. Extraskeletal chondrosarcoma was visualized as a lobulated soft tissue mass. In all cases, MR imaging accurately depicted intraosseous and soft tissue extent of tumor noted at surgery and pathologic examination. Histologic type or grade of chondrosarcoma generally cannot be characterized on the basis of visual analysis of signal intensity noted on routine MR images. However, MR imaging is excellent for exact delineation of tumor extent. PMID- 1636036 TI - Diagnostic uses of nuclear medicine in AIDS. AB - Radionuclide imaging, if applied with an organ system approach, is useful in the diagnosis of the AIDS (acquired immunodeficiency syndrome)-related complex. Specific pathologic processes can be suspected on the basis of uptake patterns. The intensity and pattern of pulmonary uptake and concomitant nonpulmonary uptake of gallium provide guidelines for distinguishing among various opportunistic pulmonary pathogens. Gastrointestinal and extra-gastrointestinal tract uptake of gallium aids distinction among fungal, mycobacterial, and viral infections and neoplasms. Patterns of spleen uptake of technetium-99m sulfur colloid and gallium allow differentiation between neoplasm (Kaposi sarcoma) and infection (with mycobacteria). Skeletal and soft-tissue abnormalities can be characterized and differentiated on the basis of bone scan and other radionuclide scan findings. Thallium uptake in brain tumors (and not in areas of infection) allows brain lesion discrimination. In the proper clinical setting, AIDS nephropathy has a characteristic gallium uptake pattern. Cardiac abnormalities (including functional) can also be assessed with scintigraphy. With knowledge of these organ specific patterns and with correlative imaging studies, the manifestations of AIDS can be differentiated and appropriate treatment instituted. PMID- 1636037 TI - Radiographic detail and variation of the nominal focal spot size: the "focal effect". AB - It is not generally appreciated that there is a gradation of the focal spot size from the anode to cathode end of an x-ray field that can dramatically affect radiographic detail from one end of a radiograph to the other. The authors name this gradation the "focal effect." Gradations in radiation intensity and focal spot size were measured from anode end to cathode end of a 14 x 17-inch field and were visually demonstrated with lymphangiograms and line-pair patterns. The degradation in spatial resolution along the anode-cathode axis was found to be as much as 75%, depending on the orientation of the patient with respect to the x ray tube. Radiographic detail is, therefore, significantly improved (even when the large focal spot is used) by exploiting the focal effect and placing the body part requiring the best radiographic detail at the anode end of the table. PMID- 1636038 TI - Performance characteristics and image fidelity of gray-scale monitors. AB - Gray-scale monitors are an essential element of electronic radiology, and their ability to provide images that are perceived to be identical to those available on conventional or laser-printed film is crucial to success of electronic radiology. Image fidelity is measured in physical characteristics (luminance, dynamic range, distortion, resolution, and noise) and with psychophysical techniques, including receiver operator characteristics analysis with clinical images and testing with contrast-detail patterns to determine threshold contrast. Currently, laser-printed images facilitate greater information transfer than does a gray-scale monitor because of their higher absolute luminance (500 ft-L vs 60 ft-L), greater perceived dynamic range, and better spatial resolution. In the near future, the developments of gray-scale monitors with 150-200 ft-L luminance, a display standard based on just noticeable differences, and algorithms to improve similarities between gray-scale display images and laser-printed images will help increase the acceptability of monitors as a means to make primary diagnoses. PMID- 1636039 TI - Electronic imaging workstations: ergonomic issues and the user interface. AB - The electronic imaging workstation serves as the interface between an electronic system and a user. Although the performance aspects of electronic displays are crucial considerations in workstation design, experience suggests that human factors in mechanical operation, software accessibility, and workstation environment are also important. Generally, workstations should have monitors arranged horizontally, and the work environment should be designed to minimize glare from lighting fixtures and to accommodate requirements for low luminance. Devices that control the workstation (eg, key pads, track balls) should be designed so that the user can operate primary and auxiliary controls with efficiency of hand and eye movements. Although many innovations in software (eg, graphical user interfaces) have allowed current workstations to be operated by users who have no knowledge of computer operations, further improvements in interactive software are necessary if such systems are to be accepted by radiologists. PMID- 1636040 TI - Systems integration: requirements for a fully functioning electronic radiology department. AB - Disparate computer-based information systems such as hospital information systems (HIS), radiology information systems (RIS), and picture archiving and communication systems (PACS) have been introduced into radiology departments at various times to meet specific operational objectives. Typically, these systems are implemented without an integration strategy. Systems integration, which optimizes integrity of data and labor savings, can be achieved by two general approaches. The first links the HIS to the PACS; the second involves interlinking of the HIS, RIS, and PACS, with the RIS as the central controlling system. Standardization in hardware, operating systems, and data base formats--which will allow true integration--is being addressed nationally and worldwide. Operational issues to resolve include ways to increase network capacity, control of data flow, and strategies for dealing with downtime. In the future, systems integration will enable prefetching, two-way interfaces, interfaces with digital dictation systems, and improved linkages with external digital input devices. PMID- 1636041 TI - Langerhans cell histiocytosis of bone. AB - Langerhans cell histiocytosis (LCH), previously called histiocytosis X, refers to a spectrum of disease characterized by idiopathic proliferation of histiocytes producing focal or systemic manifestations. Causes and pathogenesis remain unclear. However, recent studies suggest abnormal immune regulation as an important factor. The three classic syndromes may have considerable clinical overlap: eosinophilic granuloma, in which the disease is limited to bone in patients usually 5-15 years old; Hand-Schuller-Christian disease, characterized by multifocal bone lesions and extraskeletal involvement of the reticuloendothelial system (RES) usually seen in children 1-5 years old; and Letterer-Siwe disease, in which there is disseminated involvement of the RES with a fulminant clinical course in children less than 2 years old. Osseous involvement is typically in the flat bones, with lesions of the skull, pelvis, and ribs accounting for more than half of all lesions. About 30% of lesions are in long bones. Radiographic appearance of osseous LCH depends on site of involvement and phase of the disease. Early lesions appear aggressive with poorly defined margins and lamellated periosteal reaction. Late lesions appear well defined and may show sclerotic margins and expanded remodeled appearance. PMID- 1636042 TI - Characteristics and control of contrast in CT. AB - Understanding how contrast is produced and controlled in computed tomography (CT) is essential to proper application of this modality. In the typical CT scanner, a narrow x-ray beam in the section thickness direction and an air gap in the section plane are used to reduce scatter and improve contrast. High- and low contrast detectability of a CT scanner are important performance parameters contributing to optimal image quality. The limits of detectability of high contrast objects (ie, spatial resolution) are affected by detector aperture size, pixel size of the image, algorithm used to reconstruct the image, and section thickness. Visibility of low-contrast objects is limited by image noise and the algorithm. Contrast in CT images can be controlled by the window level and window width settings used to display the image. These settings dictate how the actual measurements of tissue attenuation are translated into a gray-scale image. Wide window widths can be used to provide an accurate representation of bone, and narrow widths are more useful for visualizing soft tissues. PMID- 1636043 TI - Ultrasound case of the day. Budd-Chiari syndrome. PMID- 1636044 TI - Pediatric case of the day. Pulmonary mesenchymal cystic hamartoma. PMID- 1636045 TI - General case of the day. Fibrovascular polyp of the esophagus. PMID- 1636046 TI - [Motor diagnosis in children: the correlation among three instruments]. PMID- 1636047 TI - [Kinemetric and dynamometric analysis of the motor behavior of cerebral palsy children and its changes after intensive sports and exercise therapy]. AB - Walking is one of those major everyday functions therapeutic efforts in disabled persons are aimed at, in order to maintain, or improve, their mobility. A six months intensive sports and movement therapy programme for cerebral palsied children serves to set out the potential of comprehensive gait analysis in assessing treatment effectiveness, and to present pertinent parameters for assessment. Following therapy, positive modifications of the gait pattern were found using a variety of kinematic and dynamic indicators. Moreover discussed and dealt with in some depth are the gait analysis requirements in view of assessing treatment programme effectiveness as well as comprehensive documentation of individual gait patterns. Along with the kinemetric procedures, it is in particular the dynamometric measuring methods which are outstanding in these respects, as they demonstrate very great exactness of measurement and register numerous parameters at the same time, with the data being available relatively rapidly. PMID- 1636048 TI - ["Indicators of Reha-Status (IRES)"--a patient questionnaire for assessing need and success of rehabilitation]. AB - A basic instrument is presented which enables essential parameters of rehabilitation patients' somatic, functional and psychosocial status to be brought out and data collected at a "middle level of detail" in a standardized manner, i.e. a patient questionnaire which can be used to complement medical assessment or, for example in follow-up, as a stand-alone tool. Development and testing of the instrument has been supported over the past three years by the LVA Wurttemberg pension insurance fund, both financially and conceptually. In the present article, questionnaire contents and structure are described, and validation findings reported, standardization on a representative sample of the resident population (n = 1848) is set out. The validation studies performed showed the instrument to be reliable, valid and sensitive, and meeting with good acceptance on the part of patients. Finally, a specifically designed computer programme is set out which facilitates questionnaire data input and basic analyses. Potential applications for the IRES questionnaire are for example seen in describing rehabilitation course and outcome, in documenting the effectiveness of rehabilitation measures (quality control), or in the framework of rehabilitation diagnosis, in particular relative to functional and psychosocial dimensions. PMID- 1636049 TI - [Coping and compensation strategies of patients with disseminated encephalomyelitis and of patients with schizophrenic psychoses]. AB - In ten patients with schizophrenic psychosis and ten patients with multiple sclerosis, the coping and compensation strategies were examined by means of semistructured interviewing. The following categories were considered: 1. avoidance; 2. habituation and/or adaptation to the disease; 3. efforts to compensate the deficits by will-power; 4. efforts to train certain types of behaviour; 5. self-treatment; 6. disease awareness and insight. Examples for these categories are given for both groups of patients. There is a surprising similarity in the statements made by the schizophrenic patients and those with multiple sclerosis. All of the patients with multiple sclerosis had developed coping strategies against psychological symptoms. It is suggested that the neuropsychological deficits in multiple sclerosis resemble the symptoms of reduced energetic potential observed in schizophrenia. In both groups efforts should be made to activate the compensation strategies by adequate training procedures. PMID- 1636050 TI - Encainide-induced diabetes: analysis of islet cell function. AB - OBJECTIVE: The purpose of this study was to gain insight into the mechanisms responsible for encainide-induced diabetes. Specifically, we sought to determine if absolute insulinopenia was present or whether encainide-induced diabetes was metabolically more like type II than type I diabetes. RESEARCH DESIGN AND METHODS: Islet function was assessed in a 65 year old white male with encainide induced diabetes. After 6 months of encainide treatment and 2 months duration of diabetes, C-peptide, glucagon, and glucose levels were measured at baseline and at 30 minute intervals for 120 minutes following an oral mixed meal. These measurements allowed assessment of islet beta and alpha cell function in comparison to control data from our laboratory. RESULTS: In this patient with encainide-induced diabetes, basal and peak C-peptide concentrations were similar to controls although peak C-peptide occurred substantially later than in controls. At peak glucose, the patient's C-peptide/glucose ratio was low indicating relative (but not absolute) insulinopenia. At baseline, glucagon was relatively depressed. Following Sustacal, there was an increase in glucagon of 100% over baseline compared to a mean glucagon rise in controls of only 8%. There was no serological evidence for autoimmune diabetes as islet cell autoantibodies were absent. CONCLUSIONS: Similar to other forms of diabetes, encainide-induced diabetes is a bihormonal disorder. The metabolic pattern was more like type II than type I diabetes with C-peptide secretion in the normal range, yet persistent hyperglycemia that suggests relative insulinopenia and concurrent insulin resistance. PMID- 1636051 TI - Transient postnatal elevation of norepinephrine content and turnover in brain regions of rats exposed to terbutaline prenatally: evidence for autoregulation of noradrenergic development? AB - Terbutaline, a beta-adrenergic agonist used to arrest premature labor, crosses the placenta to affect fetal nervous system development. In the current study, pregnant rats were given 10 mg/kg of terbutaline on gestational days 17, 18 and 19 and the development of noradrenergic neuronal activity was assessed in brain regions of the offspring by measuring norepinephrine content and turnover. For the latter measure, animals of different ages were given a single injection of alpha-methyl-p-tyrosine, an inhibitor of norepinephrine biosynthesis, and the decline in transmitter levels evaluated in the ensuing 2.5 hr period. Body and brain region weights were unaffected by prenatal terbutaline exposure, and norepinephrine content was unaltered during the period of drug administration. Nevertheless, the terbutaline-treated animals showed a transient elevation of both norepinephrine content and turnover in the immediate postnatal period. On postnatal day 2, turnover was increased by 50% throughout the brain, whereas effects on content were much smaller; this disparity suggests that terbutaline primarily alters nerve impulse activity (which would affect turnover more than content) rather than accelerating synaptogenesis (which would increase content equivalently to, or more than turnover). Values returned to normal by postnatal day 4 and remained so through the end of the period of synaptogenesis (day 21). The transient effects of terbutaline stand in contrast to the prolonged, and ultimately adverse effects of other drugs used in prematurity, notably glucocorticoids, and are likely to reflect a naturally-occurring, positive trophic influence of beta-adrenergic stimulation on noradrenergic development. PMID- 1636052 TI - Membrane-associated phospholipase A2 detected by a radioimmunoassay is a sensitive marker of inflammation in rheumatoid arthritis. AB - To investigate the clinical significance of membrane-associated phospholipase A2 (M-PLA2) measured by a radioimmunoassay(RIA) in rheumatoid arthritis, we examined serum M-PLA2 concentrations in 16 patients with rheumatoid arthritis. All showed elevated levels of serum M-PLA2. On the other hand, serum concentrations of C reactive protein (CRP) and IL-6 were increased in 13 (81.3%) and 14 (87.5%) of 16 patients, respectively. The serum concentrations of M-PLA2 were significantly correlated with those of CRP. These results indicate that M-PLA2 is an acute phase reactant and a sensitive and useful marker of inflammation in rheumatoid arthritis. PMID- 1636053 TI - IRFI-016, a new radical scavenger, limits ischemic damage following coronary artery occlusion in rats. AB - The effects of IRFI-016 [2(2,3 Dihydro-5-Acetoxy 4,6,7-Trimethyl-Benzofuranyl) acetic acid] a new radical scavenger were studied following six hours of myocardial ischemia, induced by left coronary artery occlusion in male rats. The loss of myocardial Creatinine Phosphokinase activity (CPK), myocardial Myeloperoxidase Activity (MPO), ECG, survival rate, and Pressure Rate Index (PRI) were evaluated in SHAM, control (vehicle i.p. injection) and IRFI-016 (200 mg/kg i.p., 30 minutes before occlusion) treated animals. CPK was significantly reduced and MPO significantly enhanced in the ischemic areas of the hearts obtained from vehicle treated rats when compared to SHAM operated ones. Pretreatment with IRFI 016 significantly attenuated (52%) loss of CPK activity in ischemic hearts and the increase in MPO activity, but did not increase PRI, thus indicating that this substance reduces the myocardial ischemic demand for oxygen. Occlusion of the coronary artery, furthermore, was associated with an immediate rise in the ST segment of the ECG, which was significantly attenuated by IRFI-016. These findings further support the important role of free radicals in the pathogenesis of acute myocardial ischemia and suggest that IRFI-016 may be a useful agent in the treatment of myocardial occlusion injury. PMID- 1636054 TI - Characteristics of covalent gossypol binding to microsomal proteins. AB - Gossypol is a potent antifertility agent contained in seeds and other parts of cotton plants. The limit set in 1974 by the FDA for this C30H30O8 compound in consumer products is 450 ppm. The binding characteristics and the nature of the microsomal protein adducts of radiolabeled gossypol were studied using centrifugation, extraction, reverse phase HPLC and filter assay approaches. Results showed a significant amount of radiolabeled gossypol to be associated with the precipitated proteins after aqueous, ethanol, acetone and ether extractions. The nature of binding of these protein adducts involved covalent, covalent but reversible (e.g., Schiff bases), and tightly-bound and trapped noncovalent residues. Non-acid labile binding adducts constituted 40% of the precipitated microsomal proteins. Eight percent of the adducts were covalent, reversible and reducible by NaBH4. A gradient HPLC separation of the acetone extracts resulted in non-gossypolone hydrophilic protein adducts with a mean retention time of 2.3 minutes. Gossypol can bind tightly to hepatic microsomal proteins with a ratio of 80 nmoles/mg protein under physiological conditions. Significant portions of these bindings are not due to simple acid labile Schiff base formation. Purer membrane preparation provided results showing predominant binding of gossypol to endoplasmic reticulum (ER) and mitochondria, followed to a lesser extent by peroxisomes and plasma membranes. Difference spectra of the gossypol-bound rat hepatic microsomal preparations and controls demonstrated a 3 nm shift from 413 to 410 nm caused by gossypol covalent-binding. Results of this study indicate that gossypol binds covalently to microsomal proteins. Its binding to membrane proteins may affect metabolism of sterols, steroids, or fatty acids. PMID- 1636055 TI - Monoisoamyl meso-2,3-dimercaptosuccinate: interaction with metallothionein-bound cadmium in vitro and evidence of active transport into renal and hepatic cells in vivo. AB - Monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS) and the unesterified 2,3 dimercaptosuccinic acid (DMSA) were evaluated for relative reactivities against metallothionein (MT)-bound cadmium (Cd) in vitro by elution of the reaction products through Sephadex G-75 gel. After 3 hr of incubation, Mi-ADMS removed about 70% of the Cd from Cd-MT, and a new peak emerged which corresponded to that obtained by elution of a 2:1 molar mixture of Mi-ADMS and Cd. Only about 15% of the Cd was removed from Cd-MT by DMSA. After 24 hr of incubation with Mi-ADMS, no evidence remained of the presence of Cd-MT; all of the Cd was recovered in a very high molecular weight fraction and in a fraction corresponding to Cd ion. In contrast, after 24 hr of incubation with DMSA, 25% of the Cd was still present as Cd-MT, while the remainder eluted in a fraction corresponding to a 2:1 molar complex of DMSA and Cd. When Mi-ADMS was administered to Cd-bearing mice which had received an inhibitor of organic anion transport, probenecid (PBC) or sulfinpyrazone (SPZ), prior to administration of the monoester, there was a marked attenuation of the Cd mobilizing actions of Mi-ADMS as reflected in whole body Cd levels. Analysis of organ Cd concentrations revealed that PBC blocked primarily the mobilization of renal Cd by Mi-ADMS, while the principal action of SPZ in antagonizing the action of Mi-ADMS was on hepatic Cd mobilization. It was concluded that Mi-ADMS has a higher affinity for Cd in Cd-MT than does DMSA, and that the access of Mi-ADMS to intracellular Cd is, at least in part, mediated by the organic anion transport system. PMID- 1636056 TI - In vivo studies on halogen compound interactions. III. Effect of carbon tetrachloride plus 1,2-dichloroethane on liver necrosis and fatty accumulation. AB - The effect of a single dose of carbon tetrachloride (CT), 1,2-dichloroethane (DCE) and the mixture on liver toxicity was investigated. The co-presence of both toxins exerts a more than additive effect on liver necrosis and on TBA-reactive substances produced by liver homogenates incubated at 37 degrees C. Both these effects are prevented in animals treated with vitamin E. The liver GSH is not involved in the synergistic action. The liver triglyceride levels of rats treated with the mixture are lower than in those treated with CT alone. This finding cannot be explained either by an improvement in the lipoprotein secretion or by the fact that the liver receives less NEFA. It is thus likely that the apparent protection against liver steatosis is the sign of more severe damage to the liver cell that partially blocks triglyceride synthesis. The mixture composed of CT+DCE exerts a potentiating action on liver toxicity with CT+DCE having the same characteristics as those, as previously reported, exerted by the co-presence of CT+DBE. PMID- 1636057 TI - In vivo studies on halogen compound interactions. IV. Interaction among different halogen derivatives with and without synergistic action on liver toxicity. AB - The liver toxicity of several halogen compound mixtures have been tested. The compounds were selected on the basis of their metabolic pathways: carbon tetrachloride (CT) and trichlorobromomethane (TCBM) undergo a dehalogenation via P450-dependent enzyme system, 1,2-dichloroethane (DCE) and 1,2-dibromoethane (DBE) are mainly conjugated with the cytosolic glutathione (GSH) by means of the GSH-S-transferase. The mixture TCBM+DBE shows a more than additive action on lipid peroxidation and liver necrosis. TCBM, like CT, reduces the hepatic level of GSH-S-transferase, increasing the amount of DBE available for cytochrome P450 dependent metabolism, with the production of toxic metabolites. Thus, the behavior of the mixture TCBM+DBE is very similar to that of the mixture CT+DBE, previously reported. Mixtures composed of CT+TCBM and DCE+DBE do not show any synergistic effect on liver toxicity. The results allow one to conclude that the toxicity of mixtures of halogen compounds can be partly predicted on the basis of their metabolic pathways. When the metabolism is quite different, a synergistic toxicity can occur if one pathway interferes with a detoxification mechanism of the other compound. If the two metabolisms are very similar they produce, at most, an additive toxicity. PMID- 1636058 TI - Antioxidant effect of calmodulin antagonists in rat brain homogenate. AB - Several calmodulin antagonists, W-7, amitriptyline, trifluoperazine, chlorpromazine, dibucaine, prenylamine, calmidazolium, and compound 48/80, inhibited lipid peroxidation induced non-enzymatically in rat brain homogenate by ascorbate and Fe2+. Suggestions of involvement of calmodulin in various oxidative cellular responses, based on experiments using calmodulin antagonists, may need to be re-evaluated. PMID- 1636059 TI - Serotonin release in nucleus of the solitary tract and its modulation by antitussive drugs. AB - The effects of antitussive drugs on the release of [3H]5-hydroxytryptamine ([3H]5 HT) were investigated in slices prepared from rat nucleus of the solitary tract (NTS) and depolarized with 30 mM KCl under superfusion conditions. Dihydrocodeine and dextromethorphan, both central acting antitussive drugs, significantly increased the release of [3H]5-HT from slices of the rat NTS. Furthermore, these antitussive drugs significantly increased the rate of turnover of the 5-HT in the brainstem. These results suggest that the effect of central acting antitussive drugs were mediated by increase of 5-HT release in the brainstem, particularly in the NTS. PMID- 1636060 TI - Conversion of mitochondrial redox state toward oxidation by prostacyclin in 70% hepatectomized rats. AB - Arterial blood ketone body ratio (KBR) and hepatic mitochondrial phosphorylation rate (PR) were investigated in partially (70%) hepatectomized rats treated with 100 micrograms/kg body weight prostacyclin (PGI2) analogue i.p. after operation and every 12 h thereafter up to 72 h. Sampling was performed at 12, 24, 48, and 72 h after operation. In sham-operated rats, KBR significantly increased from the preoperative values of 0.34 +/- 0.03 and 0.38 +/- 0.03, to 0.55 +/- 0.03 and 0.58 +/- 0.02 at 12 h in the groups with and without PGI2 treatment, respectively (P less than 0.001). KBR returned to the preoperative levels after 24 h in the PGI2 treated group, while it tended to be in the lower normal range in the untreated group. In the hepatectomized rats, KBR significantly decreased in the untreated group compared with the preoperative values and the values in the sham-operated group. It returned to the preoperative range within 72 h. In the PGI2-treated group, KBR increased significantly, to values above 0.54, after a 24-h delay and was maintained at those levels for 72 h. Concentrations of total ketone bodies (TKB) in the untreated groups remained in the upper range of preoperative values (above 200 nmol/ml) in the sham-operated rats and decreased significantly in the hepatectomized group (234 to 126 nmol/ml). TKB in the treated groups tended to decrease only in the sham-operated group (205 to 166 nmol/ml), and was massively reduced in the hepatectomized group (167 to 81 nmol/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636061 TI - Experimental selective myocardial infarction in the dog without open-chest surgery. AB - In 16 dogs, a selective myocardial infarction (MI) was experimentally provoked without open-chest-surgery by means of microspheres (MS) injected into a Judkins catheter positioned into the left anterior descending coronary (LAD) under fluoroscopy. This was shown by ECG-abnormalities, increase of the serum-enzymes of myocardial necrosis, decrease of left ventricular end diastolic pressure (LVEDP), wedge pressure, and cardiac output. After 5 weeks, thoracotomy showed a myocardial infarction limited to the anterior wall of the heart, which was of subendocardial location and consisted of multiple zones of microinfarction. Histological examination of the corresponding area showed necrosis of myocardial muscle fibres. PMID- 1636062 TI - Histopathology of experimental spinal cord trauma. Comparison of treatment with TRH, naloxone, and dexamethasone. AB - The results of treatment with thyrotropin-releasing hormone (TRH), naloxone and dexamethasone treatments albino rats with experimental spinal cord injury were compared. All the animals were made paraplegic by the application clip method of Rivlin and Tator. Treatment was administered i.p. as bolus injections in two doses, at 45 and 120 min after the injury. Animals were allocated randomly to four experimental groups: (1) TRH (0.6 mg per dose), (2) naloxone (0.8 mg per dose), (3) dexamethasone (0.6 mg per dose), and (4) control (saline). TRH-treated rats showed significantly better histopathological scores than either naloxone or dexamethasone-treated ones (Kruskal Wallis: 24.058 P less than 0.001). PMID- 1636063 TI - Photosensitization of human bladder carcinoma cells by pyrene-dodecanoic acid: quantitative analysis of the cytotoxicity. AB - The effects of photochemotherapy with the fluorescent fatty acid pyrenedodecanoic acid (P12) and long-wavelength ultraviolet (UVA) light on cells derived from human bladder carcinoma were studied. Exposure of these anchorage-dependent cells to P12 either in monolayers of adherent cells or in suspension resulted in a time related uptake of P12 and its incorporation into the cells' neutral and phospholipids. The uptake and localization of P12 was visualized with fluorescence microscopy and the distribution of the cell population with respect to P12 uptake was analyzed by flow cytometry. Irradiation of P12-containing monolayers of bladder carcinoma cells with UVA light resulted in cell killing. But, on microscopic examination no apparent cell lysis was detected, and since digestion with trypsin did not result in the dispersion of the monolayers it was impossible to assess toxicity by cell count. Alternative procedures were therefore used, and the following cell parameters were determined: (a) cellular uptake or release of chromate; (b) ability of cells to re-adhere to the substratum; and (c) the long-range proliferation potential. The combined inhibitory effect of photoirradiation on cell adherence and on their proliferative potential was utilized for determining reductions of up to 7 log in cell viability. The results obtained with five independently established in vitro bladder carcinoma cell lines indicated that these cells are susceptible to P12 induced photosensitization, suggesting that bladder malignancies might be potential candidates for pyrene-induced photochemotherapy. PMID- 1636064 TI - Reduced clearance of leukocytes from lungs in septic rats. AB - Leukocytes have previously been shown to sequestrate in the lungs and liver in association with traumatic and septic shock. In a rat model of gram-negative sepsis of intra-abdominal origin, a previously described in vivo technique was used for dynamic studies of leukocyte sequestration in different organs using white blood cells labeled with 111-indium-oxine. One group of rats was either studied immediately after induction of sepsis or for 6 h under a scintillation camera for continuous registration of the activity distribution (i.e., presence of leukocytes). Another group was studied 12 h after induction of sepsis for 60 min. The activity increased immediately over the lungs, indicating sequestration of the leukocytes during the first 6 h, but there was no significant difference in this respect between septic and control animals. It does not seem possible to study leukocyte sequestration dynamically in this way. When the labeled leukocytes were administered 12 h after induction of sepsis, however, the activity of septic animals' lungs was seen to remain elevated over the time period studied compared with control rats, in which the activity slowly decreased. In the liver and spleen, the activity increased in both groups, but significantly more so in control animals, which may be explained by disturbed leukocyte margination and cell turnover in the septic animals. This study has indicated that leukocyte distribution in different organs is affected by sepsis and this reaction can be studied using radiolabeled leukocytes. PMID- 1636065 TI - Effect of age and gender on in vivo ethanol elimination, hepatic alcohol dehydrogenase activity, and NAD+ availability in F344 rats. AB - It has been reported that aging strikingly decreases in vivo ethanol metabolism in F344 rats without major effects on hepatic alcohol dehydrogenase (ADH) activity. Because hepatic ADH activity is not always rate limiting in the oxidation of ethanol, we measured in vivo ethanol elimination rate (EER), hepatic ADH activity, and the hepatic-cytoplasmic and mitochondrial redox states after acute ethanol application in 2- and 12-month-old F344 rats of both sexes. In male, but not in female, animals EER decreased with age significantly, by 28% (P less than 0.01). The body-to-liver weight ratio was significantly increased in male (39.4 +/- 1.5 vs 46.5 +/- 2.0; P less than 0.05), but not in female, animals with age. Specific activity of ADH was not significantly changed by age, while the activity was significantly reduced with age in male, but not female, rats when related to body weight (5.1 +/- 0.4 vs 3.9 +/- 0.3 mumoles/100 g b.wt./min; P less than 0.05). The cytoplasmic, but not the mitochondrial (NAD+) to (NADH), ratio was significantly decreased with age in male livers (317 +/- 48 vs 793 +/- 128, P less than 0.05), while this was not the case in female livers. In summary, the data show a sex dependence of the effect of age on ethanol metabolism. The observed reduction in in vivo EER with age in male animals is due at least in part to an increased body-to-liver weight ratio, decreased hepatic ADH activity, and reduced availability of NAD+, the cofactor of the ADH reaction. The cause of this may be decreased transport of reducing equivalents through the mitochondrial membrane due to a lack of shuttle systems or a change in the physicochemical properties of the mitochondrial membrane, or decreased reutilization of NADH as NADPH resulting from a reduction of microsomal ethanol oxidation with age. PMID- 1636067 TI - Bladder cancer in the spinal cord-injured patient with long-term catheterization: a casual relationship? PMID- 1636066 TI - Preventive effect of beta-alanyl-L-histidinato zinc on bone metabolism in rats fed on low-calcium and vitamin D-deficient diets. AB - The effect of beta-alanyl-L-histidinato zinc (AHZ) on bone metabolism in the femoral diaphysis of rats fed on low-calcium and vitamin D-deficient diets was investigated. Rats were orally administered AHZ (10, 30, and 100 mg/kg per day) for 14 days and were killed on the 15th day. Feeding with low-calcium and vitamin D-deficient diets caused a significant decrease in serum 25-hydroxy-vitamin D3, calcium, and inorganic phosphorus concentrations. These decreases were not prevented by AHZ administration. Meanwhile, the femoral-diaphyseal calcium and phosphorus contents were significantly reduced by feeding with the deficient diets. Decrease in bone calcium content was significantly prevented by the doses of 30 and 100 mg AHZ/kg. Furthermore, the dose of 100 mg AHZ/kg produced a significant increase in bone deoxyribonucleic acid (DNA) content and alkaline phosphatase activity in rats fed on the deficient diets. Bone zinc content in the deficient rats was significantly increased by the doses of AHZ (30 and 100 mg/kg). The present results suggest that oral administration of AHZ has a preventive effect in the development of deteriorating bone metabolism in rats fed on low-calcium and vitamin D-deficient diets. PMID- 1636068 TI - Extracorporeal shock wave lithotripsy in neurologically impaired patients. PMID- 1636069 TI - The occurrence of urologic injuries in patients with gunshot wounds to the spine. PMID- 1636070 TI - Complications from long-term indwelling Foley catheters in female patients with neurogenic bladders. PMID- 1636071 TI - Continent diversion and bladder augmentation in spinal cord-injured patients. PMID- 1636072 TI - Neurourology of spinal cord-injured patients. AB - To simply perform a rectal examination is not adequate. The interpretation is of paramount importance. Often in cauda equina lesions, tone found in the sphincteric site will be misinterpreted to mean somatic reflex tone. The tone found in these low lesions with areflexic bladders is caused by the fact that the internal anal sphincters are innervated by the sympathetic fibers, which are still intact in these patients. One may often have to rule out physical tone--an intrinsic property of tissue. When performing the dermatome examination for sensation, it is important that the examiner orders the patient to close his eyes. Then the examiner hits the air only while asking the patient. "Do you feel anything now?" It is surprising how many patients will respond by saying, "I feel it!" These patients do a great deal of wishful thinking or have paresthesias or dysesthesias. If these two factors are not ruled out, the examiner can be misled. The examiner should not stimulate two sites simultaneously (eg, leaning with the elbow on the thigh of the patient while testing the anogenital dermatomes, particularly if sensation is present in the thigh). This error in technique can produce a false-positive response while pinning the anogenital sites, which may be anesthetic. It is unsatisfactory for the examiner to state that the patient has sensation without specifically stating whether it is pinprick, light touch, or even hypalgesic, especially when referring to the sacral segments. Additionally, the examiner must state whether the sensation is unilateral or bilateral. To examine only the perianal dermatomes is insufficient; the penile and scrotal dermatomes must also be examined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636073 TI - The evaluation of autonomic dysreflexia. PMID- 1636074 TI - [From obesity to diabetes or the natural history of abnormalities in the secretion and action of insulin]. PMID- 1636075 TI - [Conservative treatment of breast cancer in the early stage: factors predictive of local recurrence]. PMID- 1636076 TI - [Etiopathogenesis of paraneoplastic hypercalcemia]. PMID- 1636077 TI - [Malignant hypercalcemia: treatment]. PMID- 1636078 TI - Containing the costs of the EMF problem. PMID- 1636079 TI - Cell-transplant results under fire. PMID- 1636080 TI - NIH strategic plan nears its final form. PMID- 1636081 TI - Monkey-human viral hybrid is new weapon in AIDS fight. PMID- 1636082 TI - Scientists search for "the disappeared" in Guatemala. PMID- 1636083 TI - New genes may shed light on cell growth control. PMID- 1636084 TI - Origins and extinctions: paleontology in Chicago. PMID- 1636085 TI - Three-dimensional structure of an angiotensin II-Fab complex at 3 A: hormone recognition by an anti-idiotypic antibody. AB - The elucidation of bioactive conformations of small peptide hormones remains an elusive goal to structural chemists because of the inherent flexibility of these molecules. Angiotensin II (AII), the major effector of the renin-angiotensin system, is an octapeptide hormone for which no clear structural models exist. Peptide hormones such as AII share the property that they bind to their receptors with high affinities, in spite of the fact that they must overcome an extremely large conformational entropy barrier to bind in one conformation. A "surrogate system" that consists of a high-affinity monoclonal antibody (MAb) and AII has been used to study a bound conformation of AII. The crystallographic structure of the complex reveals a structure of AII that is compatible with predicted bioactive conformations of AII derived from structure-activity studies and theoretical calculations. In the complex, the deeply bound hormone is folded into a compact structure in which two turns bring the amino and carboxyl termini close together. The antibody of this complex (MAb 131) has the unusual property that it was not generated against AII, but rather against an anti-idiotypic antibody reactive with a MAb to AII, which renders this antibody an anti-anti-idiotypic antibody. The high affinity for AII of the original MAb to AII was passed on to MAb 131 through a structural determinant on the anti-idiotypic antibody. Strikingly, the conformation of AII in this complex is highly similar to complementarity determining region loops of antibodies, possibly indicating that a true molecular mimic of bound AII was present on the anti-idiotypic antibody against which MAb 131 was elicited. PMID- 1636086 TI - Magnetoferritin: in vitro synthesis of a novel magnetic protein. AB - The iron storage protein ferritin consists of a spherical polypeptide shell (apoferritin) surrounding a 6-nanometer inorganic core of the hydrated iron oxide ferrihydrite (5Fe2O3.9H2O). Previous studies have shown that the in vitro reconstitution of apoferritin yields mineral cores essentially identical to those of the native proteins. A magnetic mineral was synthesized within the nanodimensional cavity of horse spleen ferritin by the use of controlled reconstitution conditions. Transmission electron microscopy and electron diffraction analysis indicate that the entrapped mineral particles are discrete 6 nanometer spherical single crystals of the ferrimagnetic iron oxide magnetite (Fe3O4). The resulting magnetic protein, "magnetoferritin," could have uses in biomedical imaging, cell labeling, and separation procedures. PMID- 1636087 TI - Recognition of angiotensin II: antibodies at different levels of an idiotypic network are superimposable. AB - Genetic and sequence information are reported for an angiotensin II-reactive antibody (Ab1, MAb 110) and an anti--anti-idiotypic antibody (Ab3, MAb 131) that have identical antigen binding properties and that are related by an anti idiotypic antibody (Ab2-beta) that satisfies accepted biochemical criteria for an internal image-bearing antibody. The sequences of the variable regions of the Ab3 and of the Ab1 are nearly identical, even though the Ab1 is an antibody to a peptide and the Ab3 is an antibody to a globular protein. Significantly, amino acid residues that make critical contacts with antigen in the crystal structure of the Ab3-antigen complex are highly conserved in Ab1, suggesting that the epitopes of the Ab2-beta recognized by the Ab3 do indeed resemble the bound structure of the antigen. PMID- 1636088 TI - Identification of envelope V3 loop as the major determinant of CD4 neutralization sensitivity of HIV-1. AB - Laboratory isolates of human immunodeficiency virus type-1 (HIV-1) such as HTLV IIIB are generally T cell line-tropic and highly sensitive to neutralization by soluble CD4 (sCD4), a potential antiviral agent that is undergoing clinical trial. However, many primary HIV-1 isolates are macrophage-tropic and sCD4 resistant. Envelope V3 loop sequences derived from primary HIV-1 isolates were sufficient to confer on HTLV-IIIB not only the tissue tropism but also the degree of sCD4 neutralization resistance characteristic of their HIV-1 strains of origin. Single amino acid changes in the V3 loop enhanced sCD4 resistance by up to tenfold. These observations suggest that the tissue tropism and sCD4 neutralization sensitivity of HIV-1 isolates are regulated by similar mechanisms. PMID- 1636089 TI - Stress-induced facilitation of classical conditioning. AB - Stress has been shown to impair subsequent learning. To determine whether stress would impair classical conditioning, rats were exposed to inescapable, low intensity tail shock and subsequently classically conditioned under freely moving conditions with a brief periorbital shock unconditioned stimulus and a white noise conditioned stimulus. Unexpectedly stressed rats exhibited significantly more conditioned eyeblink responses and the magnitude of their individual responses was also enhanced. These results stand in contrast to the learning deficits typically observed and suggest that stress can enhance the acquisition of discrete conditioned responses. PMID- 1636090 TI - Establishment of stable, cell-mediated immunity that makes "susceptible" mice resistant to Leishmania major. AB - Cell-mediated, but not antibody-mediated, immune responses protect humans against certain pathogens that produce chronic diseases such as leishmaniasis. Effective vaccination against such pathogens must therefore produce an immunological "imprint" so that stable, cell-mediated immunity is induced in all individuals after natural infection. BALB/c mice "innately susceptible" to Leishmania major produce antibodies after substantial infection. In the present study, "susceptible" mice injected with a small number of parasites mounted a cell mediated response and acquired resistance to a larger, normally pathogenic, challenge. This vaccination strategy may be applicable in diseases in which protection is dependent on cell-mediated immunity. PMID- 1636091 TI - Planar induction of anteroposterior pattern in the developing central nervous system of Xenopus laevis. AB - It has long been thought that anteroposterior (A-P) pattern in the vertebrate central nervous system is induced in the embryo's dorsal ectoderm exclusively by signals passing vertically from underlying, patterned dorsal mesoderm. Explants from early gastrulae of the frog Xenopus laevis were prepared in which vertical contact between dorsal ectoderm and mesoderm was prevented but planar contact was maintained. In these, four position-specific neural markers (engrailed-2, Krox 20, XlHbox 1, and XlHbox 6) were expressed in the ectoderm in the same A-P order as in the embryo. Thus, planar signals alone, following a path available in the normal embryo, can induce A-P neural pattern. PMID- 1636092 TI - Transforming growth factor-beta in leishmanial infection: a parasite escape mechanism. AB - The course of infection with the protozoan parasite Leishmania is determined in part by their early replication in macrophages, the exclusive host cells for these organisms. Although factors contributing to the survival of Leishmania are not well understood, cytokines influence the course of infection. Transforming growth factor-beta (TGF-beta) is a multipotential cytokine with diverse effects on cells of the immune system, including down-regulation of certain macrophage functions. Leishmanial infection induced the production of active TGF-beta, both in vitro and in vivo. TGF-beta was important for determining in vivo susceptibility to experimental leishmanial infection. PMID- 1636093 TI - An eosinophil-dependent mechanism for the antitumor effect of interleukin-4. AB - Murine interleukin-4 (IL-4) exhibits potent antitumor activity when present at the site of tumor cell challenge. Associated with tumor cell death is the appearance of an inflammatory infiltrate comprised predominantly of eosinophils and macrophages, but with few lymphocytes. Antibodies that specifically block the accumulation of granulocytes at the site of inflammation were injected in vivo to define the cell type responsible for the antitumor action of IL-4. These studies implicate eosinophils in IL-4-mediated tumor cytotoxicity. The lymphoid independent nature of IL-4 action is supported by the analysis of mutant mouse strains with defined lymphocyte immunodeficiencies. The observed regression of established tumor masses by localized IL-4 action provides a rationale for exploring IL-4-mediated tumor killing as a potential therapy for human malignant disorders. PMID- 1636094 TI - Visually evoked oscillations of membrane potential in cells of cat visual cortex. AB - In response to visual stimulation, cells of the cat visual cortex fire rhythmically at frequencies between 30 and 60 hertz. This rhythmic firing can be synchronized among cells in widespread areas of the visual cortex. The visual stimulus conditions under which this process occurs suggest that the synchronization may contribute to the integration of information across broadly displaced parts of the visual field. An intricate mechanism must control the regularity of firing and its synchronization. In vivo whole-cell patch recordings from cells in area 17 have now shown that robust oscillations of membrane potential underlie the regularity of firing seen extracellularly. In the cells studied, the characteristics of the oscillations of membrane potential suggest that such oscillations are produced by rhythmic activity in synaptic inputs. These rhythmic synaptic inputs form the most likely mechanism for the synchronization of activity in neighboring cortical cells. PMID- 1636095 TI - [Anatomic characteristics of the pelvic girdle]. AB - The most recent methods of investigation (CT osteoabsorptiometry) were applied in an attempt to reconstruct from their morphological structure the way in which connections between the bones of the pelvic girdle undergo stress. Thus, both sacroiliac articulation and symphysis pubis show characteristic distribution of the subchondral bone density and layout of the tensile collagen fibrous material as expression of a strongly varying qualitative pattern of stress during walking. In the region of sacroiliac articulation are the highest subchondral densities, both at the cranial and caudal edges, whereas the central part of the two auricular surfaces is less heavily mineralized. This distribution matches the thickness of the hyaline cartilage of the joint. There are striking sexual differences in the distribution of the subchondral bone density at the bordering surfaces of the symphysis pubis. During walking, all components of sacroiliac articulation and the symphysis pubis are apparently subjected to sudden changes in stress. Independent of this, the os sacrum is constantly exposed to torque on account of the weight of the upper body, and this is balanced out by the sacrospinal and sacrotuberal ligaments. PMID- 1636096 TI - [The role of CT in diagnosis and therapy of fractures of the pelvic girdle]. AB - The conventional pelvic overview and special projections of the pelvic ring are often not conclusive for the diagnosis of pelvic ring fractures. The superimposition of multiple bony and soft tissue structures interfere with correct three-dimensional orientation of the bony lesions in spite of special projections. CT offers the possibility of identifying pelvic fractures that are not visible in conventional radiographs. Dislocated fractures can especially be appreciated. With CT, it was possible for the first time to classify lesions of the sacroiliac joint: (I) distortion (vacuum phenomena), (II) rupture of the ventral sacroiliac ligaments (open book), (III) lesions of the ventral and dorsal sacroiliac ligaments, and (IV) luxation of the os sacrum. Lesions of the sacrum can also be classified into four groups: (I) diastasis of the sacroiliac joint, (II) sacral lip fractures, (III) vertical fractures and compression fractures, (IV) comminuted fractures. Above all, the CT scan facilitates an accurate examination of the dorsal pelvic ring. Furthermore, better appreciation of intrapelvic soft tissue lesions is possible. In a retrospective study on 53 patients, in 88.7% we had quite helpful and extremely helpful CT examinations, and 90% higher precision in comparison to conventional radiographs. PMID- 1636097 TI - [Pelvic girdle fractures--must they be stabilized?]. AB - Osteosynthesis can only be successful in the pelvis if one has a biomechanical understanding of the physiological flux of force from the neck of the femur via the acetabular fossa to the sacroiliac joint. The sacroiliac ligaments have a particularly important support function here. For assessing stability and classifying the traumatic patterns it is helpful to use Pennal's classification, which takes the direction of the action of force into account. Three basic forms can be distinguished: anteroposterior compression, lateral compression and vertical avulsion. Depending on the extent of the traumatic pattern one can distinguish three subtypes. Type 1 is treated conservatively while types 2 and 3 require surgical treatment. The traumatic patterns and treatment techniques applied are described clearly and with good illustrations. PMID- 1636098 TI - [Timing of osteosynthesis in pelvic girdle injuries. Advantages and disadvantages of early surgical management]. AB - Eighty-five percent of the patients with pelvic injuries have multiple injuries; the mortality averages 40%. The frequency of laparotomy is about 35%, predominantly because of rupture of the spleen and liver and less often because of rupture of the bladder. New osteosynthesis techniques were developed in an attempt to find better means of local tamponade. After acute cheilotomy, a simple means of ventral internal fixation should always be used. Dorsal stabilization techniques, if required, should seldom be done in the acute setting. Slatis-type external fixation as an isolated mode of stabilization is insufficient in unstable injuries. PMID- 1636099 TI - [Anesthesiologic problems and specifics in the management of severe pelvic injuries]. AB - There is a close relationship between trauma of the pelvis, hemorrhagic shock, microcirculation disturbances and multiple organ failure. Of primary importance are the treatment of pain, early intubation, artificial ventilation, protection against heat loss and replacement of massive blood loss. Contrary to conventional volume replacement by electrolyte solutions, the author favors the administration of colloids, especially the new concept of "small volume resuscitation," i.e., the rapid infusion of a mixture of hypertonic saline solution and hyperoncotic dextran. Although there are limitations, the central venous and pulmonary arterial pressure reflect the volume balance of the circulation. The oxygen partial pressure of mixed venous blood, more or less reflecting the global oxygen supply state of the organism, can be measured only by means of a pulmonary artery catheter. The outcome depends greatly on optimization of the oxygen supply to a patient in shock whose oxygen needs are remarkably increased. Therapy should be aimed at keeping the arterial oxygen tension above 150 mmHg, increasing the cardiac index to 50% above normal, and stabilizing the hemoglobin concentration at an individually optimized value. PMID- 1636100 TI - [Classification and management of complex pelvic trauma]. AB - Complex pelvic traumas are pelvic fractures accompanied by pelvic soft tissue injuries. Mortality in major pelvic fractures with associated soft tissue injuries is high, and these injuries can pose a more complex range of therapeutic problems. Uncontrolled bleeding and septic complications are the main causes of death. There has been extensive work on grading pelvic ring fractures, but less attention has been paid to grading the accompanying soft tissue damage. Therefore, a grading system for pelvic injuries was developed that takes the soft tissue damage into account more than the fracture classification did when used alone. It is a point system that considers the fracture itself, the soft tissue injuries, including lesions in the pelvic organs, vessels and nerves, and the general concomitant injuries. From 1972 to 1990 the clinical course and outcome of 132 patients with complex pelvic traumas were reviewed. The mortality was 34.8%. Eighty-three of the patients (62.9%) underwent immediate laparotomy and in 68 patients (51.7%) open reduction and internal fixation of the unstable pelvic ring were performed. For better primary treatment of patients with complex pelvic injuries, a trauma algorithm is introduced. It leads to important therapeutic steps after brief clinical, ultrasonic and radiological assessments. The major questions in the flow chart take the pelvic ring and hemodynamic instability into account. Immediate laparotomy, surgical control of hemorrhage, and open reduction and internal fixation of an unstable pelvic ring represent the most important requirements for successful treatment. PMID- 1636101 TI - [Determining indications and osteosynthesis techniques for the pelvic girdle]. AB - 1566 patients with fractures of the pelvis were treated at the Department of Traumatology of the Hannover Medical School between 1972 and 1990: 1350 patients had fractures of the pelvic ring, 216 isolated acetabulum fractures, 398 combinations of pelvic ring fractures and acetabular involvement; 718 of these patients were admitted with severe polytrauma. For 1254 patients a complete file was available for clinical and radiological evaluation of fracture distribution, classification (Tile and anatomical location) and concomitant injuries. During the observation period, significant increase in the severity of the trauma, the severity of the pelvic fractures and the rate of internal stabilization, especially of the posterior pelvic ring was observed. The overall mortality after pelvic fractures was 18.1%. This mortality depended significantly on the Hannover Polytrauma Score (PTS) and the associated pelvic and extrapelvic blunt trauma. Internal fixation of pelvic fractures was performed in 195 patients. This experience has now led to standardized procedures for the different fracture locations. With the task of minimizing soft tissue trauma and reducing the implant size, more differentiated treatment of sacral fractures is now applied. Adapted small fragment implants ("local osteosyntheses") can be applied, with an unilateral longitudinal dorsal incision providing an excellent overview over the fracture line. For internal fixation of sacral fractures, involvement (penetration by screws, transfixation) of the sacroiliac joint is avoided whenever possible. In our experience early open reduction and internal fixation of pelvic fractures facilitates the management of these severely injured patients. PMID- 1636102 TI - [Complications in surgical management of pelvic fractures]. AB - In the care of pelvic injuries complications arise because of organizational and technical factors, some of which are described here. The following measures are important: autotransfusion, emptying the bladder and catheterization, checking and protection of the colon, correct management of the operation table, and prophylactic measures to avoid thrombosis. From an operational/technical point of view, it is most important that a larger with good exposure route be chosen that takes the anatomical structures into account. Of 123 cases, 20% were not ideally reduced. Twice massive bleeding occurred from the A. glutea superior, once the sacral dura was opened without any adverse effects, infection occurred 8 times and 10 times peroneal paralysis was observed. PMID- 1636103 TI - [Initial results with the ball joint fixator]. AB - The ball-joint fixator is a one-plane external fixator system that allows correction of the reduction postoperatively. Dynamic axial loading is made possible by a telescoping device. Between January 1987 and June 1991, 312 external fixators were applied in the Department of Trauma of the Surgical University Clinic in Freiburg/Breisgau. In 25 of these cases the ball-joint fixator (Unifix) was used. The study includes 16 open and 8 closed tibial fractures and 1 open femoral fracture. The pin-tract infection rate was 14%. In 16 patients a cast was necessary for a short time after the fixator had been removed, and 3 other patients needed intramedullary nailing. The long-term complications observed were osteitis pseudarthrosis and refracture (in 1 case each). The ball-joint fixator is a device that can be applied very easily and quickly. It can be used to advantage in the treatment of multiple trauma patients with open tibial fractures. Because of the fixed distance between the pin clamps there is no advantage over the original AO fixator in fractures where the telescoping mechanism cannot be used. PMID- 1636104 TI - [Effect of pin-point surface osteosynthesis plates in comparison with conventional osteosynthesis plate surfaces on the sub-implant bone tissue. Preliminary communication]. AB - Treatment of bone fractures with compression plates requires contact surfaces between the implant and bone. Because of this, there is a major nutritional disturbance in bone as a result of surgery. In an animal study of minipigs, this investigation proved that the reduced contact surfaces of periosteal bone vitality and that contact aids in the prevention of osteoporosis. Our work substantiates the conclusion that the osteoporosis underneath the smooth surface plates in the vicinity of implants is a result of cortical remodeling. This effect is believed to be induced by necrosis rather than by unloading effects. PMID- 1636105 TI - [What is the effect of para-articular fractures on hyaline joint cartilage? Experimental electron optic studies of the rabbit on post-traumatic subchondral vascularization disorders]. AB - Joint fractures can interrupt the arterial and venous blood supply to the hyaline cartilage. Previous studies revealed effects of venous engorgement and hypertension in the cartilage. In this study the influence of interruption of the blood supply on the development of osteoarthritis was analysed. In a prospective, experimental study in 40 rabbits all vessels in the patella were ligated and the cartilage was investigated after 2, 6, 12, and 24 weeks by transmission electron microscopy. After 2 weeks no degenerative signs were determined. After 6 weeks there were distinct signs of cartilage injury. The degeneration of the hyaline cartilage increased with time. The endpoint of injury was the destruction of the cartilage and necrosis of the chondrocytes, determined after an ischaemic period of 24 weeks. The stages of cartilage degeneration in our trial correspond to the changes that are well known to occur in osteoarthritis. In conclusion, interruption of the blood supply of the patella results in degenerative changes to the joint cartilage. This effects is related to the duration of ischaemia. On the basis of results we recommend early and watertight repositioning of fractured joints not only for biomechanical reasons but also to avoid irrevocable effects of interrupted blood supply on hyaline joint cartilage. PMID- 1636106 TI - [Craniocerebral trauma and aseptic osteonecrosis. Steroid-induced sequelae after therapy of brain edema]. AB - In this publication we present three cases of avascular osteonecrosis (AON) of the femoral head and the talus in adolescent and young adult patients following short-term, high-dose steroid therapy for cerebral trauma. All patients were proven to be free of other risk factors for AON. The latency period between the steroid therapy and the occurrence of AON ranged from 12 to 60 months; steroid therapy lasted for 12 to 16 days with a total dosage equivalent to 2370-7180 mg prednisolone. Our case reports are added to a review of the literature with 14 similar cases reported receiving short-term, high-dose steroid therapy; 2 of them were also after brain trauma. To the best of our knowledge, 1 of our cases shows the longest latency period ever described after such therapy, and all our cases had a shorter therapy time than reported by other authors who have mentioned brain trauma patients. Additionally, bilateral necrosis of the talus due to short term, high-dose steroid therapy has also not previously been described. Whereas AON is quite common after long-term steroid therapy (e.g., for immunosuppression and rheumatic disorders), our cases prove that serious complications can occur even after a short period of emergency steroid therapy in cerebral trauma, a possibility that is generally unknown. The minimal dosage and the maximum time steroids can be applied to exclude the risk of AON has not yet been determined, although we do recognize that steroids are useful for the prevention of brain edema.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636108 TI - [A modified procedure for repositioning shoulder dislocation]. AB - A new method is presented for the reduction of shoulder dislocations and dislocation fractures, together with the follow-up results. This procedure is a modification of a method for reduction of the hip. Examination of our patients 1 3 years after the accident showed no sign of nerve lesions and little residual discomfort. PMID- 1636107 TI - [Radiologic diagnosis of cervical spine injuries]. AB - This investigation was designed to evaluate the radiological methods used for diagnosis of cervical spine injuries. In the time from 1977 to 1990, a total of 102 patients with 113 fractures or fracture-dislocations of several segments of the cervical spine were diagnosed and treated in the University Surgical Clinic in Graz; 36 of these patients had lesions of the upper cervical spine and 66, lesions of the lower cervical spine. All trauma patients with disturbances of consciousness or neck discomfort reported on questioning or elicited by palpation underwent three-view radiographic screening for cervical spine injuries (lateral, AP and open-mouth views). This led us to suspect cervical spine injuries in all 102 patients. Computerized tomography was performed in 76 cases, which yielded additional information in 55 cases about the middle and posterior column and the adjacent vertebral bodies. In 13 cases conventional tomograms were important to confirm the diagnosis of dens fracture. Except for the diagnosis of hanged-man and dens fractures, computerized tomography is accepted as the second step for the evaluation of cervical spine injuries. We performed 8 investigations with magnetic resonance imaging in 7 patients, and noted spinal cord lesions of low signal intensity in 3 of these cases. PMID- 1636109 TI - [Distraction of the first metacarpal bone for thumb reconstruction]. AB - After amputation of the thumb good functional results can be achieved by lengthening the first metacarpal bone, if a suitable technique is used. Since 1987 we have treated six patients in this way. In all of our patients the thumb was mechanically stable and sensitive after lengthening, thus improving the patients' ability to use their hands for grasping. Other advantages include the relative simplicity of the method, the fact that no experience of microsurgery is necessary and that the surgery does not result in soft tissue damage. In most cases treatment is on an outpatient basis. Between the various operations the patient can be reintegrated into his professional and social life. The period of absence from work (about 12 weeks) is relatively short when the severity of the injury is taken into consideration. Distraction of the first metacarpal bone cannot be considered an alternative to replantation but represents a complementary procedure in accordance with the modern management of severe hand injuries. PMID- 1636110 TI - [Post-traumatic recurrent hip joint dislocation]. AB - Recurrent post-traumatic dislocation of the hip joint without an accompanying fracture is very rare. Delayed reduction and a too short immobilization periods seems to favor redislocation. One case is presented together with a discussion of the operative therapy and the intraoperative pathological-anatomical findings with respect to the literature. PMID- 1636111 TI - [Computerized tomography follow-up of the ante-torsion angle after femoral shaft fractures in the adult]. AB - Rotational deformities are common complications following fractures of the femoral shaft. Computed tomography for determination of the anteversion angle of the femoral neck has proved to be the most suitable way of quantifying rotational faults. Out of our inpatient collective, 45 patients who had undergone interlocking intramedullary nailing of the femur and 10 in whom dynamic compression plating had been performed were examined by clinical investigation and computed tomography. Patients impression and clinical findings proved to be less reliable. Computerized determination of the anteversion angle showed rotational deviations of more than 10 degrees in 18 patients with interlocking nails and in 3 with dynamic compression plates. According to our investigations, rotational deviations less than 20 degrees will not usually handicap the patient. Therefore, we suggest that use of the term "rotational fault" be restricted to deviations exceeding 20 degrees compared with the uninjured side. PMID- 1636112 TI - [Mechanical properties of PDS-augmented patellar tendon transplants in reconstruction of the anterior cruciate ligament]. AB - In 25 sheep the anterior cruciate ligament (ACL) was reconstructed after resection. Twelve modified "Jones procedures" were performed (transplantation of the central third of the patellar tendon with an initial load of 50 N) and 13 polydioxanone (PDS) augmentations. In 15 cases the ACL was resected from the right knee. Twenty-one sheep survived for 1 year and were then evaluated. Loss of the ACL leads to instable joints in this experiment. Within the first 6 months anterior translation occurs; after 1 year subluxations can be seen on the X-ray films. Macroscopical signs of extensive arthrosis were seen in the femorotibial and femoropatellar joints; the menisci were totally destroyed. Macroscopically strong ligaments were seen 1 year after PDS-augmented reconstruction as well as after transplantation of the patellar tendon with an initial load of 50 N. There was no difference between the two groups. The mechanical strength reached 54% of the maximum load of a control group in the Jones reconstructions and 61% after additional augmentation with a 2-mm biodegradable PDS cord. There was no statistically significant difference. Both methods are suitable for reconstruction of the ACL; the patellar tendon replaces the ACL very well. PMID- 1636114 TI - AIDS: A review for the hepatologist. PMID- 1636113 TI - [Bilateral subcutaneous rupture of the quadriceps tendon caused by minor trauma. A case report]. AB - A case of bilateral simultaneous rupture of the quadriceps tendons resulting from minor trauma is reported. The etiology, diagnosis and therapy are discussed. PMID- 1636115 TI - Structure and function of the human immunodeficiency virus type 1. PMID- 1636116 TI - Epidemiology of human immunodeficiency virus infection and the acquired immunodeficiency syndrome. PMID- 1636117 TI - Neoplasms of the gastrointestinal tract and hepatobiliary system in acquired immunodeficiency syndrome. PMID- 1636118 TI - Diagnostic considerations in the human immunodeficiency virus-infected patients with gastrointestinal or abdominal symptoms. PMID- 1636119 TI - Enteric immunologic abnormalities in human immunodeficiency virus infection. AB - The intestinal mucosa is an important portal of entry of HIV, and HIV-infected mononuclear cells are found in the intestinal lamina propria of 30 to 50% of HIV infected patients even at early stages of the disease. HIV infection of epithelial cells has not consistently been detected and is still controversial. Intestinal T cells are phenotypically and functionally distinct from circulating T cells, especially in their state of activation and differentiation, which both affect the replication and cytopathicity of HIV. An increase in CD8+ cells and variable decreases in CD4+ cells have been found in the intestinal lamina propria by immunohistologic studies, resulting in a decreased CD4 to CD8 ratio; in addition, CD25 expression is reduced. Changes in intraepithelial lymphocytes are unclear. B-cell differentiation seems to be disturbed because IgA plasma cells and IgA2 secretion are reduced. Depletion or functional impairment of activated mucosal lamina propria lymphocytes by HIV infection could explain the breakdown of the mucosal immune barrier leading to opportunistic diseases; in addition, due to the interrelationship between mucosal immune system and epithelium, these changes might be responsible for the partial bowel atrophy and maturational defects in enterocytes of HIV-infected patients. PMID- 1636121 TI - Human immunodeficiency virus infection of the liver. PMID- 1636120 TI - Wasting in the acquired immunodeficiency syndrome. PMID- 1636122 TI - Hepatic histopathology in the acquired immunodeficiency syndrome. AB - Involvement of the liver with the same opportunistic organisms and neoplasms affecting other organs has been recognized since the beginning of the AIDS epidemic. In this overview of hepatic histopathologic features in AIDS, we review the range of opportunistic infections and neoplasms accompanying HIV infection. Hepatic disease may result from viral, bacterial, protozoal, or fungal infection, or secondary to drugs and neoplasms. Liver involvement in AIDS usually reflects disseminated rather than primary disease. CMV and mycobacteria are the most common organisms in liver identified in biopsy and autopsy studies. A variety of nonspecific features, including steatosis, granulomas, and sinusoidal abnormalities may also be seen. HIV-1 itself was recently identified in the liver. Speculation regarding the significance of this finding has been discussed in this review. Hepatitis B, C, and D may also complicate the course of disease in patients with AIDS. Hepatitis B behaves differently in the population with AIDS than in immunocompetent patients. We concluded our review with a discussion of the present recommendations regarding the use of liver biopsies in these patients. This topic continues to be widely debated in the literature. PMID- 1636123 TI - Human immunodeficiency virus-associated biliary tract disease. PMID- 1636124 TI - A 29-year-old man with the acquired immunodeficiency syndrome and liver dysfunction. PMID- 1636125 TI - Neural transplantation: an approach to cellular plasticity in the developing central nervous system. PMID- 1636126 TI - Surfactant protein regulation and diabetic pregnancy. PMID- 1636127 TI - Cellular timing of fetal lung development. PMID- 1636128 TI - Hypoxic responses of the neonatal endothelium. PMID- 1636129 TI - Matrix receptors and development. PMID- 1636130 TI - Ontogeny of nonimmune defense mechanisms. PMID- 1636131 TI - Salmonella infections of the abdominal aorta. AB - Salmonella accounts for up to one-third of all primary abdominal aortic infections. During the past ten years, we have treated three patients with this disease and have reviewed an additional 61 instances found in the English literature. The overall survival rate was 46 percent. Fever and back or abdominal pain were present in more than 90 percent of the patients, while a pulsatile mass was present in only 42 percent of those reported. Blood cultures were positive in 73 percent of patients. Computed tomography and angiography were helpful in delineating the presence of aneurysms and defining the extent. Twenty-two patients were treated without undergoing aortic resection; there were no survivors. One patient had an aortic resection without reconstruction and survived. Twenty-eight patients were treated with aortic resection and anatomic reconstruction. Six patients in this group died of graft sepsis and an additional six patients required graft removal for persistent infection. In contrast, 18 of 19 patients treated with extra-anatomic grafting and aneurysm resection survived, with only one death from aortic stump sepsis. No patient has required graft removal for sepsis. These results suggest that aneurysm resection and extra anatomic bypass is the treatment of choice in patients with Salmonella infections involving the infrarenal aorta. PMID- 1636132 TI - A comparison of outcome after resection for squamous cell carcinomas and adenocarcinomas of the esophagus and cardia. AB - Among 625 patients with squamous cell carcinoma and 134 patients with adenocarcinoma of the esophagus and cardia, a one stage resection was performed upon 375 patients of the squamous carcinoma group (excluding pharyngolaryngoesophagectomy) and 92 patients in the adenocarcinoma group. The patients formed the basis of the current analysis. Male to female ratio was 7:1 for those with squamous carcinoma compared with 3.6:1.0 for those with adenocarcinoma (p = 0.037). Most squamous carcinomas were located in the middle one-third (56.3 percent) and lower one-third (33.0 percent) of the esophagus. Adenocarcinomas were predominantly found at the cardia (91.3 percent) and lower one-third (6.5 percent). Postoperatively, respiratory complications occurred in 34.4 percent of patients in the group with squamous carcinoma and in 19.6 percent of patients in the group with adenocarcinoma (p = 0.01). Cardiac complications occurred in 28.3 percent of patients in the group with squamous carcinoma and in 16.3 percent of patients in the group with adenocarcinoma (p = 0.03). Anastomotic leaks were uncommon for both groups (4.3 and 5.4 percent, respectively). Anastomotic recurrence occurred in 6.1 and 7.6 percent of patients, respectively. Respiratory complications, malignant cachexia and sepsis accounted for most of the deaths in the hospital. The 30 day mortality rates for patients with squamous carcinoma and adenocarcinoma were comparable (4.8 and 6.5 percent, respectively) (p = 0.33). After 30 days, mortality rates differed significantly (11.7 and 3.3 percent, respectively) (p = 0.026). The overall hospital mortality rates, however, were comparable (16.5 and 9.8 percent, respectively) (p = 0.14). The overall five year survival rate for both groups was 15 percent. For patients with squamous carcinomas, the five year survival rate after curative resection was 31 percent compared with 5 percent for palliative resection. For patients with adenocarcinomas, the respective five year survival rates were 35 and zero percent. It was concluded that the two types of tumor differ significantly in the incidence of postoperative morbidity, but mortality and the long term survival rates were similar. PMID- 1636133 TI - A prospective randomized double blind study of perioperative antibiotic use in the grafting of ulcers of the lower extremity. AB - We conducted a prospective, randomized, double blind study of the use of a perioperative antibiotic in the skin grafting of arterial and venous ulcers of the lower extremity. Ninety-four patients were randomized and 90 were available for analysis. There was no statistically significant difference in graft "take" or incidence of recipient site infection in the antibiotic versus the no antibiotic group. PMID- 1636134 TI - Treatment of calculi of the common bile duct. AB - Endoscopic sphincterotomy (EST) is regarded as an alternative therapeutic approach to the surgical treatment of choledocholithiasis. To clarify the indication for each of these two methods, a prospective study has been performed comparing patients with calculi of the common bile duct who had undergone endoscopic or surgical treatment. Mortality, morbidity and stone clearance were used as criteria for the evaluation of the dependence of age on results achieved by the two modalities. Of 306 patients with choledocholithiasis, 199 underwent surgical exploration of the duct and 107 underwent endoscopic sphincterotomy. Patients who were more than 60 years of age and had previously undergone cholecystectomy underwent endoscopic sphincterotomy. All other patients had surgical treatment. There were no significant differences among the two groups with regard to mortality rates. The incidence of relevant complications as well as the incidence of surgical revisions related to postoperative complications in the operation group was, however, significantly higher (p less than 0.05). In contrast with this, the incidence of retained stones was significantly lower (p less than 0.01) in the group that underwent surgical treatment (2.5 percent) than in the group that had endoscopy (11.2 percent). When assessing the results in terms of stone clearance, complications and mortality rates, findings seem to indicate that a safe limit for the application of surgical treatment would be 60 years of age, whereas older patients should be primarily considered as candidates for EST. PMID- 1636135 TI - Reflux esophagitis and carcinoma. AB - Early detection of a malignancy in reflux esophagitis should permit an effective surgical action if a causal time relation between reflux, esophagitis and carcinoma exists. In the medical literature on tumors of the esophagus associated with reflux esophagitis, it has been reported that they are adenocarcinomas in most instances. Squamous carcinomas are seldom mentioned. In a population of patients with five squamous carcinomas and 13 adenocarcinomas associated with reflux, three squamous carcinomas had developed on stage III or on a stenotic esophagitis and two squamous carcinomas were at the upper limit of a Barrett's esophagus. The 13 adenocarcinomas were associated with a Barrett's esophagus. No carcinoma was found to be associated with a low grade esophagitis. During the same time period, 224 patients were operated upon for a serious documented esophagitis (stage III, stenotic, Barrett's esophagus), including the 18 patients with carcinoma. Five hundred and thirty-four patients were operated upon for a lower grade esophagitis, with no associated carcinoma and 592 patients were operated upon for carcinoma of the esophagus. The five squamous carcinomas associated with reflux were resected and classified T1 N0. The 13 adenocarcinomas associated with reflux were resected and classified T1 N0 M0 (two patients), T2 N0 M0 (two), T3 N0 M0 (five), T3 N1 M0 (one patient), T3 N2 M0 (one) and T3 N3 M0 (two patients). Four patients with squamous carcinomas were alive after two, six, nine and 15 years. Eight patients with adenocarcinomas were alive after two years (one patient), three years (two patients), four years (three), five years (one patient) and seven years (one). Three carcinomas were diagnosed by routine endoscopy. The mean age of the patients with carcinoma associated with reflux was older than in the general carcinoma series, the relative number of females was higher and the use of alcohol and tobacco was not as frequent, but the differences were not significant. In squamous and columnar carcinomas, a long history was significant (p less than 0.001); in Barrett's esophagus, loss of weight (p less than 0.01), intestinal epithelium (p less than 0.001) and dysplasia (p less than 0.01) were also significant. In one patient, carcinoma was discovered during the follow-up evaluation of an antireflux procedure for Barrett's esophagus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1636136 TI - Total exenteration, two or one ostomy. AB - Total exenterations require fecal and urinary diversions, necessitating ostomies in the anterior abdominal wall. This article was done to explore the possibility of extremely low anastomoses of the intestine to the anal stump, to reduce the number of ostomies to only one for the urinary diversion. Although technically feasible, the long term follow-up evaluation of these patients resulted in us having reservations concerning function. PMID- 1636137 TI - Patient characteristics, methods of diagnosis and treatment of melanoma in the United States. AB - The American College of Surgeons performed a patient care and evaluation study of melanoma for 1981 and 1987 to determine the presenting symptoms, methods of evaluation, clinical management and resulting outcome. Melanomas of the skin, eye, mucous membrane, metastases with unknown primary site and miscellaneous sites were included. Details concerning 5,004 patients from 681 hospitals in the study in 1981 and 6,900 patients from 844 hospitals in the study in 1987 were obtained--most melanomas were located in the skin; a decline in symptoms occurred at initial diagnosis; an increase in age at first diagnosis was reported; most melanomas were in Caucasian patients; slightly more melanomas occurred in men than women; more melanomas occurred in men on the head and neck and trunk, and more in the lower extremity in women; most tumors were not large in diameter; a significant shift was reported to lower levels of Clark's invasion, and a significant amount of unknowns existed in the Breslow's thickness of invasion. The large number of unknowns makes analysis difficult, but there seems to be some shift toward thinner levels of Breslow's in tumors in which it was known, from 1981 to 1987. Only a small proportion of patients in the current series was known to have node involvement or known distant metastases. An overall decline in diagnostic studies occurred between 1981 and 1987. PMID- 1636138 TI - The course of severe foot infection in patients with diabetes. AB - Infection of the foot is a limb threatening condition for patients with diabetes mellitus. Identification of patients with diabetes and severe infection of the foot most likely to benefit from early revascularization or major amputation would improve the results of a treatment policy to prevent limb loss and avoid futile delays in amputation. During a nine year period, 79 diabetic patients underwent emergency procedures for severe infection of the foot during the initial hospitalization period. None of the patients underwent arterial reconstruction. Eventually, 21 of the patients required a major amputation, eight during the initial hospitalization and 13 on a subsequent admission. Stepwise discriminant analysis of clinical independent variables revealed that the patients most likely to require a major amputation during the initial hospitalization were those with an absent dorsalis pedis pulse and a polymicrobial infection (p = 0.018). The overall amputation rate (immediate or subsequent amputation) was higher for patients of either sex with nonpalpable pedal pulses when compared with those with at least one palpable pulse (p less than 0.05). Males who were not dependent on insulin had the highest risk of overall limb loss (p = 0.01). Patients undergoing delayed amputation required a significantly higher number (p = 0.01) of readmissions to the hospital for recurrent infection of the foot than those who did not undergo amputation. Data in the current study suggest that early major amputation in a subset of patients would prevent delay in the rehabilitation process of the amputee, decrease long term morbidity and reduce health care cost. An aggressive policy of early revascularization in patients with a pulse deficit may reduce the amputation rate in those with diabetes with severe infection of the foot. PMID- 1636139 TI - Achieving local control for inflammatory carcinoma of the breast. AB - A single institution, retrospective study of 28 patients with inflammatory carcinoma of the breast treated from 1984 to 1990 was performed. Patients received two to four cycles of cyclophosphamide, doxorubicin and 5-fluorouracil (CDF) and were then evaluated for mastectomy. Mastectomy was accomplished in 26 patients after CDF. In 21 patients, the breast was resectable after the initial doses of chemotherapy and modified radical mastectomy was done. Radiation therapy was given to 16 of the 21 patients after six to nine cycles of postoperative chemotherapy. The remaining five of 26 patients had a marginal response to CDF and underwent preoperative radiation therapy. Local recurrence occurred in four of five patients receiving preoperative radiation, in three of 16 receiving postoperative radiation and in one of five receiving mastectomy without radiation therapy. The overall observed five year survival rate was 18 percent, with a median of 34 months. Neither dermal lymphatic invasion nor estrogen receptor status were statistically significant variables when analyzing patients for local recurrence or survival. Despite poor long term survival results, the combination of induction CDF, mastectomy and postoperative radiation achieved local control in 81 percent of patients. PMID- 1636140 TI - Postprandial peptide YY release is mediated by cholecystokinin. AB - Peptide YY (PYY), a 36 amino acid peptide, is a member of the structurally and functionally related pancreatic polypeptide (PP) family of gastrointestinal and neurally active peptides. Peptide YY is released postprandially from the distal small intestine and colon and has been shown to inhibit many physiologic actions of cholecystokinin (CCK), an integral foregut hormonal stimulant of pancreatic and gastric secretion. The specific signals for the release of PYY have not been ascertained, although foregut signals, both neural and hormonal, are likely. In this study, we evaluated the possible role for CCK in postprandial PYY release in eight conscious dogs. Conscious dogs were given a fat meal or a one hour intravenous infusion of CCK-8. On separate days, the dogs were pretreated with the specific CCK receptor antagonist L-364,718. Peripheral blood samples were collected for radioimmunoassay for PYY, PP and neuropeptide Y. The fat meal and exogenous CCK stimulated PYY and PP release, effects that were abolished by pretreatment with the CCK receptor antagonist. The results provide support for a physiologic role of CCK in the mediation of postprandial PYY and PP release. Furthermore, an inhibitory feedback loop is suggested between the hindgut (PYY) and the foregut (CCK). PMID- 1636141 TI - Carcinoma arising in Barrett's esophagus. AB - During the period 1971 and 1990, 500 patients underwent resection for carcinoma of the esophagus, 51 of whom had an associated Barrett's esophagus. Of these, 49 had adenocarcinoma and two had squamous cell carcinoma. Barrett's carcinoma accounted for 23.7 percent of the surgically treated adenocarcinomas during this period. Reflux symptoms were present in 13 patients preoperatively. Tumors developed in four patients who had undergone previous antireflux operation and in two patients on the surveillance program. By postresection staging, 18 patients had stage II tumors and 33 patients had stages III and IV tumors. Stage and length of the tumor were the only prognostic determinants. The overall 90 day hospital mortality rate was 17.6 percent. The hospital mortality rate before 1986 was 22.9 percent, but decreased to 6.3 percent in the last five years. The one, two and five year survival rates were 45.9, 25.0 and 13.6 percent, respectively. The five year survival rate was significantly greater for patients with stage II (25 percent) than for patients with stages III and IV (4.5 percent) (p less than 0.05) and for tumor length less than 6 centimeters (21 percent) than for tumors greater than 6 centimeters (zero percent; p less than 0.001). PMID- 1636142 TI - Modified suburethral sling procedure for treatment of recurrent or severe stress urinary incontinence. AB - The most suitable material used to perform suburethral sling procedures for recurrent or severe stress urinary incontinence remains controversial. A comparison was made between two commonly used materials, synthetic Gore-Tex (expanded reinforced polytetrafluoroethylene) and autologous fascia lata. Both groups showed improved urethral pressure profiles postoperatively, but there was no difference in the magnitude of change between groups. The objective cure rate at six months for the Gore-Tex group was 100.0 versus 87.5 percent for the fascia lata group (p = 0.155). While there was no statistical difference between the incidence of de novo detrusor instability or length of postoperative bladder drainage (p = 0.104 and p = 0.978, respectively), there was a trend toward more postoperative complications of urinary obstruction in the Gore-Tex group. PMID- 1636143 TI - A new double-turn one-hand knot. AB - The technique of making a one-hand double or triple turn thrust of a suture is described. The advantage of the technique is the low risk of gliding of the first thrust and the decreased need of assistance. PMID- 1636144 TI - Total hepatic mesh wrap for hemostasis. AB - To improve hemostasis and avoid the complications of perihepatic packing, a technique of hepatic tamponade using total mesh wrap is reported. The method is geometrically, technically and mechanically feasible and appears to be effective in controlling severe parenchymatous bleeding. PMID- 1636145 TI - A new technique to correct vascular steal secondary to hemodialysis grafts. AB - Three patients are described who developed symptomatic steal distal to hemodialysis grafts, documented by angiodynography. Intraoperatively, the graft was plicated to increasing depths while using angiodynography over the radial and ulnar artery. When the flow became antegrade, the plication was stopped, resulting in salvageable grafts. Using the technique, all three patients had long use of the graft after the steal was corrected. PMID- 1636146 TI - Immunologic associations of keloids. AB - The mechanisms underlying the pathogenesis of keloids have not been fully characterized despite extensive past and present research. Results of past and present studies have shown that the immune system is actively involved in the development of these lesions. Future investigations into the biochemistry and immunologic factors of keloids are anticipated and expected to produce additional insight. The inability to identify cellular (fibroblast) abnormalities has led most investigators to focus on the humoral regulators of wound healing, that is, biochemical substances, immunologic mediators and growth factors. Future studies are needed to confirm or refute the presence of AFA. AFA, if they exist, may prove to be useful as immunologic markers of keloids and may help distinguish keloids from hypertrophic scar in the early stages of wound healing. The influence of immunologic mediators may be more impressive early in the development of scars. "Young" or "early" is defined as less than two years of age, whereas "old" or "late" keloids are more than two years of age. We suggest that future studies stratify keloids into early versus late and also measure the rates of collagen synthesis of fibroblasts derived from the normal and abnormal specimens from the same patient. Analysis of the leukocyte factors will clarify the role the immune system has in the regulation of collagen synthesis. Preliminary investigations have shown that immunotherapy may be of value in the treatment of keloids. The role of fibroblast heterogeneity needs to be investigated. It is not known which aspects of fibroblast heterogeneity are responsible for the localized and accelerated rates of collagen synthesis of keloid fibroblasts. PMID- 1636147 TI - Exigent postinjury thoracotomy analysis of blunt versus penetrating trauma. AB - We reviewed the recent experience with urgent thoracotomy performed in the operating room (OR) to compare the relative indications and injury pattern after blunt versus penetrating trauma. Among 2,316 patients admitted with acute trauma of the chest, excluding 319 undergoing thoracotomy at the emergency department, 83 required urgent OR thoracotomy; 27 patients (3 percent) sustained blunt trauma, 32 (4 percent) had stab wounds (SW) and 24 (7 percent) had gunshot wounds (GSW). The indications for operation after blunt trauma were shock (48 percent) and angiographically defined great vessel injuries (48 percent). For SW, thoracotomy was done for tamponade (50 percent), excessive chest tube output (28 percent) or shock (15 percent), and for GSW, thoracostomy output (50 percent), shock (25 percent) or tamponade (12.5 percent). Descending thoracic aorta (DTA) or other arch vessel tears were confirmed in 48 percent of patients with blunt trauma requiring thoracotomy; the remaining had pulmonary (31 percent) or cardiac wounds (7 percent). The most frequently encountered injuries in patients with SW were cardiac (46 percent) and pulmonary (37 percent), while the patients with GSW had predominantly pulmonary (72 percent) and cardiac (14 percent) injuries. The surgical management of blunt versus penetrating chest trauma differs with respect to the indications for urgent thoracotomy as well as the underlying injury pattern. The most common indication for urgent thoracotomy after penetrating injuries was excessive chest tube output (37.5 percent). Excluding torn DTA, only 14 of 822 patients (1.7 percent) admitted with blunt chest trauma required urgent thoracotomy and 13 of these patients (93 percent) presented in a state of refractory shock because of active thoracic hemorrhage. Thus, in contrast with penetrating wounds, urgent thoracotomy for blunt trauma is rarely justified on the basis of chest tube output alone. PMID- 1636148 TI - Muscarinic M2-selective ligands also recognize M4 receptors in the rat brain: evidence from combined in situ hybridization and receptor autoradiography. AB - We have used autoradiographic techniques to examine the characteristics and distribution of the binding of reported selective M2 muscarinic ligands and compared them with the distribution of cells expressing mRNAs for the different subtypes of muscarinic receptors. Our results suggest that the M2 ligands used in the present study ([3H]OXO-M, ([3H]OXO-M,[3H]AF-DX384,AF-DX116, methoctramine) also recognize M4 receptors present in regions such as the striatum and olfactory tubercle. This is supported by 1) relative abundances of the different transcripts, with m2 mRNA being very scarce and m4 mRNA very abundant in these regions; 2) comparison of the pharmacological characteristics of M2-ligand binding sites in brain areas selected by their exclusive expression of M2 receptors versus areas enriched in M4 receptors. An important conclusion of these studies is that none of the muscarinic radioligands available at the present time appears to label specifically a single muscarinic receptor subtype population. Areas are suggested where autoradiographic techniques can be helpful in elucidating the subtype selectivity of existing and new ligands. PMID- 1636150 TI - Evidence for GABAergic interneurons in the red nucleus of the painted turtle. AB - Immunocytochemical and electrophysiological evidence supporting the presence of GABAergic interneurons in the turtle red nucleus is presented. Injections of HRP into the spinal cord produced labeling of large neurons in the contralateral red nucleus. The peroxidase-antiperoxidase (PAP) method revealed smaller cells immunoreactive to an antibody against glutamate decarboxylase (GAD), the synthetic enzyme for the inhibitory neurotransmitter GABA, that were interspersed among larger immunonegative neurons. Similar small neurons were densely immunostained by antibodies to GABA-glutaraldehyde conjugates obtained from different sources and applied according to pre-embedding and postembedding protocols. Rubrospinal neurons retrogradely labeled with HRP measured 16 and 27 microns in mean minor and major cell body diameters, while GABA-like immunopositive neurons situated within the red nucleus measured 7 and 13 microns. There was very little overlap in soma size between the two cell populations. Therefore, we suggest that the GAD- and GABA-positive neurons may be local inhibitory interneurons. This notion is further supported by observations of pre embedding immunostaining for GAD and postembedding immunostaining for GABA showing that the turtle red nucleus is amply innervated by immunoreactive axon terminals. These puncta are closely apposed to cell bodies and dendrites of both immunonegative large neurons and immunopositive small neurons. Moreover, immunogold staining at the electron microscopic level demonstrated that GABA-like immunoreactive axon terminals with pleomorphic synaptic vesicles formed symmetric synapses with cell bodies and dendrites of the two types of red nucleus cells. These ultrastructural features are commonly assumed to indicate inhibitory synapses. A moderately labeled bouton with round vesicles and asymmetric synapses was also observed. In addition, the two types of red nucleus neurons received asymmetric axosomatic and axodendritic synapses with GABA-negative boutons provided with round vesicles, features usually associated with excitatory functions. To obtain electrophysiological evidence for inhibition, intracellular recordings from red nucleus neurons were conducted using an in vitro brainstem cerebellum preparation from the turtle. Small, spontaneous IPSPs were recorded from 7 out of 14 red nucleus cells studied. These morphological and physiological results provide strong support for concluding that the turtle red nucleus, like its mammalian counterpart, contains GABAergic inhibitory interneurons. While we have not identified the main source of input to these interneurons, in view of the scarce development of the reptilian cerebral cortex, this input is unlikely to come from the motor cortex as it does in mammals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1636149 TI - Long-term frontal brain metabolic changes in cocaine abusers. AB - Neurological complications from cocaine use are well recognized. We propose that chronic cocaine use can also cause clinically silent brain dysfunction. We investigated brain glucose metabolism with positron emission tomography (PET) and 2-deoxy-2[18F] fluoro-D-glucose (FDG) in 21 neurologically intact chronic cocaine abusers (C) and 18 normal controls (N). The cocaine abusers were tested 1-6 weeks after the last use of cocaine and seven were retested after a 3 month drug-free period. Global cerebral glucose metabolism was not significantly different between controls and cocaine abusers (N = 38.4 +/- 3, C = 36.5 +/- 5 mumol/100 g of tissue, min). However, cocaine abusers had significantly (P less than 0.05) lower metabolic activity in 16 of the 21 left frontal regions and 8 of the 21 right frontal regions. These decreases persisted after 3-4 months of detoxification and were correlated with the dose (P less than or equal to 0.01) and the years of cocaine use (P less than or equal to 0.05). This study shows reduced rates of frontal metabolism in neurologically intact cocaine abusers that persist even after 3-4 months of detoxification. PMID- 1636151 TI - ATP-sensitive K+ channels mediate an IPSP in dorsal horn neurones elicited by sensory stimulation. AB - Nociceptive dorsal horn neurones, which are involved in the processing of pain related information, are inhibited by input from vibration-sensitive, large diameter primary sensory fibres (Wall and Cronly-Dillon, 1960; Salter and Henry, 1990a,b). We have reported previously that the inhibition of spinal nociceptive neurones by vibration is mediated by adenosine acting through P1-purinergic receptors (Salter and Henry, 1987). In a number of different types of cell, adenosine is known to activate K+ currents (Gerber et al., 1989; Greene and Haas, 1985; Proctor and Dunwiddie, 1987; Segal, 1982; Trussell and Jackson, 1987) and we have recently found that the adenosine-mediated inhibition of nociceptive neurones by vibration is the result of an inhibitory postsynaptic potential (IPSP), which is, indeed, caused by a K+ conductance (De Koninck and Henry, 1988, 1992). It has been reported that adenosine-activated K+ channels in cardiac muscle cells are the ATP-sensitive K+ channels (Kirsch et al., 1990). Therefore, we questioned whether these channels might mediate the purinergic IPSP we have observed in nociceptive dorsal horn neurones. We report here that glibenclamide, a blocker of ATP-sensitive K+ channels (Ashcroft, 1988; Schmid Antomarchi et al., 1987a,b), blocks the inhibition of nociceptive neurones by vibratory stimulation when this compound is administered locally by iontophoresis or systemically by intravenous injection. In addition, direct intracellular injection of ATP was found to block the IPSP evoked by vibratory stimulation. These data indicate that the purinergic IPSP in nociceptive spinal neurones is mediated via ATP-sensitive K+ channels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636152 TI - Oscillation of interspike interval length in substantia nigra dopamine neurons: effects of nicotine and the dopaminergic D2 agonist LY 163502 on electrophysiological activity. AB - The rates and patterns of discharge activity exhibited by 16 spontaneously active substantia nigra pars compacta dopamine neurons were studied in halothane anesthetized rats using three types of quantitative measures: 1) mean discharge rates, 2) population characteristics of interspike interval samples, and 3) interspike interval time-series measures which were used to examine patterns in the ordering of interspike intervals. The mean discharge rate of these 16 cells was 2.9 +/- 0.3 spikes/sec, and each cell was classified as bursting (25% of the cells) or non-bursting (75%). The distribution of interspike intervals of non bursting neurons were more normally distributed. Time-series analyses (raw time series plots, return maps, and phase portraits) revealed a substantial oscillatory tendency in the magnitudes of consecutive interspike intervals in these neurons under baseline conditions: Successive interspike intervals tended to alternate between short and long durations, although short bursts often occurred. Under baseline conditions, these cells exhibited both multispike bursts and consecutive long intervals less frequently than would have been predicted by chance ordering of the interspike intervals. These results imply that there are mechanisms acting to reduce the probability of these types of events. Locally infused nicotine enhanced discharge rates in these neurons. Burst firing increased in four neurons, while five neurons did not show any change in burst firing. LY 163502 induced significant decreases in both discharge rate and bursting activity in all cells tested. The variation coefficient, skew, and kurtosis of the interspike interval distributions were not consistently altered by either drug. The local infusion of either nicotine or LY 163502 decreased the oscillatory phenomenon seen in the baseline condition. Neither the nicotine or LY 163502 time-series data exhibited a larger proportion of long-short and short long pairs (relative to the median interval) than would be expected by chance. It is hypothesized that these neurons have intrinsic mechanisms, made manifest under anesthesia, which induce oscillations in interspike interval length. The oscillatory effect of these mechanisms can be overridden by tonic increases in either excitatory or inhibitory tone. PMID- 1636153 TI - Ounce of care worth tons of cash. PMID- 1636154 TI - Leadership ... requires tow E's. PMID- 1636155 TI - [Quality control in thoracic roentgen images]. PMID- 1636156 TI - [Lung radiology]. AB - Specific clinical problems of the lung ask for evaluation by specific imaging methods. Chest radiography, although still fundamental, is used more carefully, whereas computed tomography, nuclear medicine methods, MRI and angiography all contribute to answer specific questions. PMID- 1636157 TI - [Imaging methods in musculoskeletal radiology]. AB - Musculoskeletal disorders can be examined by conventional radiography, nuclear bone scan, computerized tomography, ultrasound and magnetic resonance imaging. The potentials and limitations of each method determine the individual application, depending whether the etiology, the extension or the follow-up of a bony lesion is evaluated. PMID- 1636158 TI - [Ultrasound diagnosis of the abdomen]. AB - Ultrasonography is the method of first choice for the rational work-up of abdominal pathologies. The results and limitations of this method for diagnosis of diseases of the gallbladder, bile ducts, liver, pancreas, spleen, kidney and urinary tract, adrenal glands, vessels and lymph nodes, female pelvis and gastrointestinal tract are presented in a short overview. Particular reference is made to a critical approach, emphasizing relevant further investigations. PMID- 1636159 TI - [Radiation protection in diagnostic radiology]. AB - For every diagnostical X-ray radiation exposure the applied dose has to be limited to the smallest possible value. Within the scope of a general Swiss survey it has been found that in the various medical practices and hospitals the applied doses varied quite strongly. The main reasons leading to an overdose were the operating conditions of the X-ray and film processing equipment, the film and foil materials and improper filming techniques. The applied single dose served as a measure for the radiation protection assessment of diagnostical X-ray exposures. To prevent this in the future, individual patients who are exposed to unnecessary radiation loads should be regularly checked in quality-ensuring tests. PMID- 1636160 TI - Safety of virus inactivated antithrombin III concentrate antithrombin III immuno (AT III). AB - In a prospective clinical trial the risk of infection after application of virus inactivated antithrombin III concentrate ANTITHROMBIN III IMMUNO (AT III) was investigated in patients undergoing cardiovascular surgery. The study was conducted according to the recommendations of the International Committee on Thrombosis and Hemostasis (ICTH), with the exception that most patients required additional blood products as well as AT III. Twenty-seven patients were eligible to test for the risk of acquiring hepatitis B. Twenty-six patients could be evaluated in terms of hepatitis NANB transmission considering ALT-levels whereas 20 patients could be tested for anti-HCV one year after surgery. Samples from 78 patients could be monitored for anti-HIV-1. None of these patients showed any signs of infection. AT III IMMUNO seems to be an antithrombin III concentrate with low or absent infectivity. PMID- 1636161 TI - Effects of 9, 12, 15-octadecatrien-6-ynoic acid on the metabolism of arachidonic acid in platelets and on platelet aggregation. AB - An acetylenic fatty acid: 9,12,15-octadecatrien-6-ynoic acid (dicranin) was extracted from Dicranum Scoparium and preincubated with platelets which were then stimulated by exogenous arachidonic acid (20:4 n-6). This molecule at 10(-4) M weakly inhibited the cyclooxygenase activity as assessed by measurement of 12 hydroxy-heptadecatrienoic acid (HHT) In contrast, the 12-hydroxy-eicosatetraenoic acid (12-HETE) synthesized by the 12-lipoxygenase was strongly increased by about 650%. The same effects were observed with 10(-5) M and with 10(-6) M of dicranin but to a lesser extent. Platelet hydroxylated dicranin metabolites were also found and the structure of the main compound determined by GC-MS was a 13-hydroxy derivative. Its origin has not yet been elucidated. Platelet aggregation induced by 1 microgram/ml of U46619, a structural PGH2 analogue was completely abolished in the presence of dicranin. Platelet aggregation induced either by thrombin or by arachidonic acid was inhibited by 10(-4) M of dicranin only after preincubation. This observation indicates that the formation of metabolites of dicranin are necessary to effect this inhibition. Dicranin is thus a new inhibitor of platelet aggregation and may prove to be useful for elucidating the effects of 12-HETE in biological systems. PMID- 1636162 TI - Pharmacokinetics of two pasteurized factor VIII concentrates by different and multicenter assays of factor VIII activity. AB - We assessed the pharmacokinetic characteristics of a new high-purity pasteurized FVIII concentrate in comparison with an intermediate purity pasteurized concentrate, produced by the same manufacturer. The study was designed as a cross over single-dose pharmacokinetic investigation in 8 non-bleeding patients with severe hemophilia A. All patients were given 25 IU/kg of each of the two concentrates, with an interval of at least one week between the two administrations. Decay curves were assessed by collecting 10 serial blood samples over 36 hours following the end of infusion. The concentration of Factor VIII in blood samples was determined in triplicate in three different laboratories using each of the following assay methods: a one-stage clotting assay, a two-stage clotting assay, and a two-stage chromogenic-peptide substrate assay. All pharmacokinetic parameters were calculated by model-independent methods. The two products were found to differ significantly both in the clearance, which was on average 13.8% lower for Haemate P, and in the in-vivo recovery, which was 11.7% lower for Factor VIII:C P on the average. In comparison with previous pharmacokinetic data obtained from other heated Factor VIII concentrates, the clearance of Haemate P was found to be significantly slower, while the half-life of both products was longer. No differences were observed in the Vd-area. These findings indicate that the purification procedures to which both products are subjected do not increase the in-vivo rate of plasma disappearance of Factor VIII. PMID- 1636163 TI - Possible role of plasminogen activator inhibitor 2 in the prevention of the metastasis of gastric cancer tissues. AB - The concentrations of urinary type plasminogen activator (u-PA), plasminogen activator inhibitor 1 (PAI-1), and PAI-2 were measured in gastric cancer tissues and adjacent healthy mucosal tissues. Levels of u-PA, PAI-1 and PAI-2 were higher in cancer than in control tissues. PAI-1 levels were higher together with the progression of cancer however there were no differences in u-PA or PAI-2 levels. Tumors with higher PAI-1 and lower PAI-2 levels tend to metastasize to remote lymph nodes. When the numbers of involved lymph nodes were analyzed, tumors with the large number of metastatic lymph nodes showed higher PAI-1 and lower PAI-2 level. No difference was shown in u-PA levels among these groups. These tendencies were more significant in patients with progressed gastric cancer. These results suggest that tumor with higher PAI-2 levels tend to localize or have less tendency to metastasize to lymph nodes. On the other hand PAI-1 was generally higher in tumor with invasion into nearby tissue or with nodal metastasis. PMID- 1636164 TI - Influence of oxygen radicals generating agents on eicosanoid metabolism of human endothelial cells. AB - Human umbilical venous endothelial cells were incubated with increasing concentrations (0.001-10 mmol/l) of H202 or cumene hydroperoxide. PGI2 was released within the first five minutes, whereas a significant increase in TXA2 release was not observed before 10 minutes after stimulation. Furthermore the content of intracellular ATP and the level of cytosolic free Ca2+ were measured. Doses of 0.01 mmol/l H202 or cumene hydroperoxide increased the intracellular ATP level. Doses higher than 0.1 mmol/l led to a decrease of ATP. The cytosolic free calcium (Ca2+) increased on stimulating the cells with 0.1 mmol/l cumene hydroperoxide between 120 and 240 seconds after stimulation, whereas 0.1 mmol/l H202 had no effects. These data give strong evidence, that eicosanoid-synthesis is directly started by oxygen radicals, followed by an elevation of intracellular free Ca2+. PMID- 1636165 TI - LPS-induced, but not interferon-gamma-induced procoagulant activity of suspended human macrophages is followed by a refractory state of low procoagulant expression. AB - Monocyte-derived macrophages cultured under a variety of conditions were assessed for expression of procoagulant activity (PCA) upon induction by various triggers, using a semiautomated turbidimetric recalcification time assay in a kinetic ELISA reader. Macrophages cultured in a nonadherent (teflon) culture system and seeded in microtiter plates responded with PCA expression to lipopolysaccharide (LPS), to toxic shock-syndrom toxin-1 (TSST-1) and to surface-bound IgG, but not to surface-bound albumin, nor to interferon-gamma (IFN-gamma). In contrast, macrophages stimulated in teflon containers by IFN-gamma showed a strong PCA response peaking around 24 hr after stimulation, but they failed to secrete tumour necrosis factor (TNF). Suspended IFN-gamma-stimulated cells showed a similar response upon 2nd stimulation by LPS or IgG after adherence to microtiter plates as did nonprimed counterparts. In contrast, cells primed in suspension, then cultured in adherence secreted dramatically enhanced amounts of TNF when compared with nonprimed cells. Macrophages stimulated in suspension with LPS showed a PCA response of similar magnitude, which was accompanied by TNF secretion. PCA of both IFN-gamma-primed and LPS-exposed suspension culture cells was largely due to the surface expression of tissue factor, and to a lesser extent of a prothrombinase-like activity, as evidenced by PCA testing with factor X-deficient plasma. The kinetics of LPS-induced PCA differed from IFN-gamma induced PCA, in that PCA peaked at 6 hr and fell to insignificant levels after 24 hr. When transferred to microtiter plates at this time, they could be restimulated neither with LPS, nor with surface-adherent IgG nor with IFN-gamma. Evidence was obtained that the failure to express PCA was due to a refractory state of the cells rather than to the generation of cell-bound or secreted inhibitors of coagulation. The loss of PCA expression could be prevented by pre exposure to IFN-gamma. Thus, PCA expression may be dissociated from other functional and/or activation parameters (e.g. TNF secretion). For the first time, a state in which cells are completely unresponsive to PCA induction has been identified. Should lower LPS concentrations also be found to induce such a refractory state, our results may be of pathophysiological significance. PMID- 1636166 TI - Determination of soluble fibrin: a comparison of four different methods. AB - The determination of soluble fibrin (SF) in plasma was compared using four different methods. The SF-ELISA immunologically measures the concentration of desAA- and desAABB-fibrin while the SF-tPA-test is based on activation of plasminogen by tissue plasminogen activator (tPA) in the presence of fibrin; the SF-PS-turbidimetry assay relies on the protamine sulphate (PS) -induced aggregation of fibrin in plasma whereas the SF-erythrocyte-agglutination-test (SF EAT) detects soluble fibrin by its aggregation with fibrin monomers attached to test erythrocytes. Soluble fibrin was generated in vitro by addition of thrombin or ancrod to plasma. In these experiments the soluble fibrin values of the four methods correlated well with each other and with the fibrinopeptide A release, especially in ancrod-induced fibrinogen turnover (r greater than 0.93). This high correlation is remarkable, considering the fact that the methods are based on different principles. Detection of thrombin-induced soluble fibrin was more sensitive; differences between ancrod and thrombin action were observed as well, probably due to different forms of soluble fibrin. A delayed increase of SF-PS turbidimetry values in particular during the thrombin action can be attributed to a lack of detectable aggregation of soluble fibrin at low concentrations due to its solubility in plasma. Subsequently, soluble fibrin was measured in samples from patients. The SF-ELISA and SF-tPA-test were highly sensitive and correlated better than the other methods with each other, but all correlations were less satisfactory compared with the in vitro studies. These weaker correlations might be explained by the heterogeneity of soluble fibrin determined by inter- and intraindividually varying concentrations of fibrinogen and its different derivatives in plasma samples from patients. All methods provided reliable results with differences in sensitivity, specificity and practicality. The SF-tPA test, SF-PS-turbidimetry, and SF-EAT are practical methods for routine use whereas the SF-ELISA is a highly reliable and by far the most sensitive and specific method thus offering new insights into pathogenesis of fibrinaemia and related diseases. PMID- 1636167 TI - Diagnostic efficacy of the D-dimer assay in disseminated intravascular coagulation (DIC). AB - The D-Dimer (D-D) assay for measuring cross-linked fibrin degradation products is now available for the clinical laboratory. We combined this assay with other tests to assess patients with diagnosed or suspected DIC. Also, a small group of patients (20) with deep venous thrombosis (DVT) were studied. The D-D test, antithrombin-III assay, FDP titer, fibrinopeptide-A level, protamine sulfate test, fibrinogen, prothrombin time, and activated partial thromboplastin time were used. The D-D test was abnormal in 93.7%, the AT-III level was abnormal in 87.5%, the fibrinopeptide-A level was abnormal in 89.5%, and the FDP titer was elevated in 83.7% of patients with DIC. When assessing patients found not to have confirmed DIC the D-D assay was abnormal in 20%, the AT-III level was abnormal in 6%, and the fibrinopeptide-A level was elevated in 13%. We conclude the D-Dimer assay to be a useful molecular marker of hemostasis in diagnosing DIC and this test will often discriminate between those patients with or without DIC, especially when used with the AT-III and fibrinopeptide-A assays. Of the battery of tests used in this study, the most useful, in descending order of efficacy, appear to be the D-dimer assay (93.7% abnormal), the fibrinopeptide-A titer (89.5% abnormal), the AT-III level (87.5% abnormal), and the FDP titer (83.7% abnormal). Of the global tests, the diagnostic efficacy of the prothrombin time activated partial thromboplastin time, and protamine sulfate test were no greater than chance and appear to be of little use in aiding in a diagnosis of DIC. Also, the D-Dimer assay is similar in cost to the FDP titer and is cost effective for the routine clinical laboratory. PMID- 1636168 TI - Factor XIIIA2/XIIIB2 ratio in severely traumatized patients with soft tissue trauma. PMID- 1636169 TI - Purification of bovine histidine-rich glycoprotein. PMID- 1636170 TI - "Rebleeding" the reversal of shear stress activation of platelets--a possible clue to thrombogenesis. PMID- 1636171 TI - Spatial and temporal regulations in helicoidal extracellular matrices: comparison between plant and animal systems. AB - This paper proposes an overview of the last few years' investigations regarding the helicoid formation in extracellular matrices (ECMs). Despite the architectural polymorphism displayed among the layered ECM throughout the living kingdom, helicoidal structures are often described in ECMs and appear as an optimal mechanical device. Helicoids correspond to complex two-phases composites, formation and regulation of which are still a source of debate. Taking the time event into consideration, it is clear that helicoid in ECMs are regulable structures. On the other hand, analogies with helicoidal formations in cholesteric liquid crystals strongly support the hypothesis of involvement of self-assembly processes. Therefore the balance between self-assemblies and cell regulation is questioned. By gathering animal and plant data on the topic and by analysing the characteristics of these helicoids in ECMs, it is clear that cells have the necessary machinery to interfere with the self-assembly processes in response to physiological or mechanical mechanisms. They are able to modify the physicochemical conditions outside the plasma membrane, therefore acting on the pattern of self-assembly. Several mechanisms are proposed to explain sudden variations occurring in the helicoidal formation with time. PMID- 1636172 TI - The interphase microtubule cytoskeleton of five different phenotypes of microvessel endothelial cell cultures derived from bovine corpus luteum. AB - The interphase microtubule cytoskeleton of five different microvessel endothelial cell cultures, recently established from bovine corpus luteum, was analysed using anti-tubulin immunofluorescence. An antibody against acetylated microtubules detected four cell types each of which possessed a single cilia. The length of the cilia were up to 10 microns for cell types 1 and 2. Ciliary stubs had a length of up to 0.37 microns in cell types 4 and 5. Cilia were missing in cell type 3. Long and short cilia were located in the perinuclear region from where cytoplasmic microtubules radiated. Cell type 3 displayed straight microtubules rather than the wavy path seen in the other cell types. The amount of tyrosinated microtubules visualized by a specific antibody was consistently higher than that of posttranslationally acetylated microtubules. The latter were more apparent in cell types 4 and 5 than in the other cell types. We conclude: Differences in the cytoplasmic microtubule inventory of each microvessel endothelial cell type points at individual functions maintained in culture. PMID- 1636174 TI - Carotid endarterectomy: a continuing cause for concern. Background. PMID- 1636173 TI - Production of neutrophil-specific lipid chemoattractant activity by cultured endothelial cells: heterogeneity dependent on species, ligand, or endothelial cell site of origin. AB - Previous studies have demonstrated that the interaction of cultured bovine aortic and pulmonary arterial endothelial cells and the proinflammatory vasoactive amines histamine, serotonin, and angiotensin II, causes production of three novel lipid neutrophil-specific chemoattractants that are distinct from other phospholipid or lipid neutrophil chemoattractants. In this study, we investigated the species and site specificity of this inflammatory response by incubating human aortic and pulmonary arterial endothelial cells with histamine, serotonin, and angiotensin II and assaying the supernatants for their effect on neutrophil migration. Each of these vasoactive amines caused production of neutrophil chemoattractant activity in a concentration dependent manner in both cell types. For each amine, production was blocked by a specific antagonist: cimetidine for histamine, methiothepin for serotonin-stimulated aortas, ketanserin for serotonin stimulated pulmonary arteries, and saralasin for angiotensin II. In each case, all chemoattractant activity partitioned into the organic phase and resolution by HPLC yielded two chemotactic lipids. As with the lipid chemoattractants produced by bovine endothelial cells, these lipids did not coelute with PAF, LTB4, 5-HETE, or 15-HETE, nor did they increase lymphocyte or monocyte migration. The pattern of chemotactic activity following resolution by HPLC was similar in both human aortic and pulmonary arterial endothelial cells, but was different from that of bovine aortic and pulmonary arterial endothelial cells in that only two chemoattractant lipids appeared; the third chemotactic lipid was never produced. These studies demonstrate that human endothelial cells may actively participate in neutrophil enriched local inflammatory responses by production of neutrophil specific chemotactic factors. They also suggest this response may be dissimilar depending on the site and species from which the endothelial cells originate. PMID- 1636175 TI - Symptomatic carotid artery stenosis: a solvable problem. North American Symptomatic carotid Endarterectomy Trial. PMID- 1636176 TI - Nearing the finish line? The asymptomatic Carotid Atherosclerosis Study. PMID- 1636177 TI - Aortogenic embolic stroke: a transesophageal echocardiographic approach. AB - BACKGROUND AND PURPOSE: We studied the frequency and grade of atherosclerotic changes in the thoracic aorta and their significance as embologenic lesions in patients with stroke. METHODS: Using transesophageal echocardiography, we evaluated complicated lesions in the thoracic aortas of 62 patients who met our clinical criteria for embolic stroke. A complicated lesion was defined as a raised lesion with an irregular surface or acoustic shadow based on a comparative study of echocardiographic and histopathologic findings. The results were compared with plain radiographic findings and in some cases with computed tomographic or aortographic findings. RESULTS: Twenty-six patients (42%) showed complicated aortic arch lesions on echocardiogram. Transesophageal echocardiography brought us more abundant information than other techniques. Aortic knob calcification by plain radiography correlated well with the presence of echocardiographically complicated lesions, suggesting its utility for rough screening of atherosclerotic changes. Fifty-two patients had other potential embolic sources in the heart or cervical arteries. Among the remaining 10 patients without extra-aortic embolic sources, three showed complicated lesions and were diagnosed as having aortogenic embolic stroke. CONCLUSIONS: Aortic atherosclerosis should be recognized as an embolic source of stroke and the advantage of transesophageal echocardiography recognized in its evaluation. PMID- 1636178 TI - Reproducibility of noninvasive ultrasonic measurement of carotid atherosclerosis. The Asymptomatic Carotid Artery Plaque Study. AB - BACKGROUND AND PURPOSE: To determine the effect of a lipid-lowering agent and/or a low-dose antithrombotic agent on the progression of early-stage carotid atherosclerosis, noninvasive B-mode ultrasound was used to measure intimal-medial thickness in asymptomatic individuals with moderately elevated lipids as part of the ongoing multicenter Asymptomatic Carotid Artery Plaque Study. METHODS: Uniform ultrasonic scanning and reading protocols were implemented to obtain maximum intimal-medial thickness measurements in 12 standard segments in patients having a small to moderate wall thickness (1.5-3.5 mm) in at least one of the carotid arteries. Paired B-mode image recordings on 858 patients, performed 1 month apart and read at a core laboratory (each pair by the same reader), determined both within-sonographer (W, n = 405) and between-sonographer (B, n = 453) reproducibility. RESULTS: The primary end point (mean +/- SD), defined in each individual as the mean value of the 12 maximum intimal-medial thickness measurements, was 1.31 +/- 0.21 mm (W) and 1.32 +/- 0.22 (B) at the time of the second examination. The mean difference in the primary end point (exam 2-exam 1) was -0.01 +/- 0.13 mm (W) and 0.00 +/- 0.15 mm (B). The Pearson correlation coefficients were 0.79 (W) and 0.75 (B). In 90% of the patients, the absolute difference in the primary end point was less than 0.22 mm (W) and less than 0.24 mm (B). Variability of the secondary end point, defined as the single largest intimal-medial thickness measurement in a patient, was between three and four times larger than the variability for the primary end point. Differences in sonographer performance between clinical centers were very small. CONCLUSIONS: The results demonstrate that standardized noninvasive ultrasonic techniques yield highly reproducible measures of carotid intimal-medial thickness, which can serve as a measure of carotid atherosclerosis in clinical trials that monitor small rates of lesion progression. PMID- 1636179 TI - Short-term prognosis of stroke due to occlusion of internal carotid artery based on transcranial Doppler ultrasonography. AB - BACKGROUND AND PURPOSE: The clinical course of stroke due to occlusion of the internal carotid artery is influenced by amount of collateral flow. We measured mean frequency shifts in the middle cerebral artery by transcranial Doppler ultrasonography to determine its prognostic value. METHODS: Patients with proven extracranial occlusion of the internal carotid artery and ipsilateral hemispheral stroke were enrolled in our study. We performed transcranial Doppler ultrasonography on 31 patients within 48 hours after the stroke onset and followed up 25 patients in 28 days. At the same time, neurological examination with quantification of neurological deficit was done. We correlated values of flow frequency shifts on the side of stroke with degree of neurological deficit at the onset and at 28 days as well as the degree of clinical improvement and the value of frequency shifts. RESULTS: We found a negative correlation between blood flow frequency shifts in the middle cerebral artery and degree of neurological deficit at the onset (Spearman rank correlation coefficient, -0.567; p less than 0.001). We also found a positive correlation between the change of the neurological deficit during follow-up and frequency shifts at the onset (Spearman rank coefficient, 0.548; p less than 0.05). CONCLUSIONS: Diminished blood flow velocity (mean frequency shift) in the area of stroke is a negative prognostic factor for the degree of neurological deficit at the onset and a negative prognostic factor for possible improvement. Knowledge of hemodynamic conditions in the stroke area may help to improve therapeutic decisions. PMID- 1636180 TI - Transcranial Doppler correlation with cerebral angiography in sickle cell disease. AB - BACKGROUND AND PURPOSE: Cerebral infarction in sickle cell disease is associated with arterial narrowing or occlusions of intracranial arteries. Primary stroke prevention would be feasible if a noninvasive screening test could be developed to detect intracranial disease in patients before symptoms develop. METHODS: To determine the sensitivity and specificity of transcranial Doppler in detecting significant (greater than or equal to 50% lumen diameter reduction) intracranial arterial lesions, we compared transcranial Doppler and cerebral angiography in a primarily young, symptomatic group of 33 patients (18 males and 15 females) with sickle cell disease. RESULTS: From a total of 34 examinations, transcranial Doppler detected significant abnormalities in 26 of 29 (sensitivity 90%, specificity 100%). Five were normal by both techniques. The transorbital examination detected abnormalities in two patients whose studies were otherwise unremarkable. CONCLUSIONS: Transcranial Doppler is sensitive and specific for the detection of arterial vasculopathy of sickle cell disease. Screening should include a transorbital examination of the distal internal carotid artery as well as examination using the transtemporal approach. PMID- 1636181 TI - Serum autoantibodies in patients with Alzheimer's disease and vascular dementia and in nondemented control subjects. AB - BACKGROUND AND PURPOSE: In this study we sought to evaluate the clinical significance of serum autoantibodies to dementing processes. METHODS: We assessed 40 age-matched subjects: 10 patients with probable Alzheimer's disease, 10 with possible Alzheimer's disease with cerebrovascular disease, 10 with vascular dementia, and 10 nondemented control subjects. Serum from each subject was tested for the presence of antithyroglobulin antibody, thyroid antimicrosomal antibody, gastric anti-parietal cell antibody, anti-smooth muscle antibody, antinuclear antibody, rheumatoid factor, antineuronal antibody, and anticardiolipin antibody. In addition, we investigated the sera of these patients for the presence of an antivascular antibody directed against the vascular basement membrane proteoglycan antigen and for circulating immune complexes. RESULTS: Autoantibodies were present in 100% of the patients with possible Alzheimer's disease with cerebrovascular disease, 80% of those with vascular dementia, 40% of those with probable Alzheimer's disease, and 30% of the nondemented control subjects. The highest number of autoantibodies was observed in patients with vascular dementia and possible Alzheimer's disease with cerebrovascular disease. Antinuclear antibody was present in 60% of vascular dementia patients and antineuronal antibody in 50% of these patients. However, no individual autoantibody could differentiate Alzheimer's disease from cerebrovascular disorders. Immune complexes were detected in the serum of 20-30% of each patient group. Neither the patient nor the control sera was found to contain antiendothelial antibody. CONCLUSIONS: Despite the relatively small number of individuals examined in each category, the elevated number of autoantibodies associated with possible Alzheimer's disease with cerebrovascular disease and vascular dementia indicates a possible link between the presence of autoantibodies and cerebrovascular disorders in dementia. PMID- 1636182 TI - Measurement of motor recovery after stroke. Outcome assessment and sample size requirements. AB - BACKGROUND AND PURPOSE: The purpose of this study was to analyze recovery of motor function in a cohort of patients presenting with an acute occlusion in the carotid distribution. Analysis of recovery patterns is important for estimating patient care needs, establishing therapeutic plans, and estimating sample sizes for clinical intervention trials. METHODS: We prospectively measured the motor deficits of 104 stroke patients over a 6-month period to identify earliest measures that would predict subsequent motor recovery. Motor function was measured with the Fugl-Meyer Assessment. Fifty-four patients were randomly assigned to a training set for model development; 50 patients were assigned to a test set for model validation. In a second analysis, patients were stratified on basis of time and stroke severity. The sample size required to detect a 50% improvement in residual motor function was calculated for each level of impairment and at three points in time. RESULTS: At baseline the initial Fugl Meyer motor scores accounted for only half the variance in 6-month motor function (r2 = 0.53, p less than 0.001). After 5 days, both the 5-day motor and sensory scores explained 74% of the variance (p less than 0.001). After 30 days, the 30 day motor score explained 86% of the variance (p less than 0.001). Application of these best models to the test set confirmed the results obtained with the training set. Sample-size calculations revealed that as severity and time since stroke increased, sample sizes required to detect a 50% improvement in residual motor deficits decreased. CONCLUSIONS: Most of the variability in motor recovery can be explained by 30 days after stroke. These findings have important implications for clinical practice and research. PMID- 1636183 TI - Platelet-activating factor acetylhydrolase in plasma lipoproteins from patients with ischemic stroke. AB - BACKGROUND AND PURPOSE: Platelet-activating factor is a potent bioactive phospholipid and may play an important role in occlusive vascular diseases. To assess the inactivation of this autacoid in plasma, we measured platelet activating factor acetylhydrolase activity in plasma low density and high density lipoproteins from patients with ischemic stroke. METHODS: Low density and high density lipoproteins were separated by ultracentrifugation from plasma of 33 patients with cerebral thrombosis and 31 age-matched healthy control subjects, and platelet-activating factor acetylhydrolase activity in each fraction was assayed. RESULTS: The average values of platelet-activating factor acetylhydrolase activity in low density lipoprotein from patients and control subjects were 41 +/- 18 and 29 +/- 17 nmol/ml per minute, respectively, and the difference was statistically significant (p less than 0.01 U test). There was no difference in activity in high density lipoprotein between the two groups (16 +/- 11 versus 14 +/- 9 nmol/ml per minute, respectively). CONCLUSIONS: The increased plasma platelet-activating factor acetylhydrolase activity in stroke patients is primarily attributable to the increased binding to low density lipoprotein, and this increase may be an adaptation to the augmented generation of platelet activating factor in ischemic stroke. PMID- 1636184 TI - Stroke risk from alcohol consumption using different control groups. AB - BACKGROUND AND PURPOSE: Our aim in this study was to investigate the relation between chronic alcohol consumption and stroke. METHODS: A case-control study was carried out using two hospital-based control groups and the results of a community-based survey of alcohol consumption. Hospital-based control subjects were chosen either from "general" medical admissions or a subset of "select" admissions that excluded possible alcohol-related admissions. Cases were selected from hospital inpatients. RESULTS: The relative risk for stroke associated with alcohol consumption greater than 300 grams per week for general control subjects was 0.73 (95% confidence interval [CI], 0.54-3.49) compared with 1.30 (95% CI, 0.42-4.05) for select control subjects. The odds ratio was further increased to 1.93 (95% CI, 0.87-4.28) using data from the community-based survey. None of these estimates were statistically significant. CONCLUSIONS: These results illustrate how the risk associated with alcohol consumption varies depending on the choice of control groups and may explain the contradictory results from previous case-control studies. Because of different biases associated with control selection, we believe that the results of this study are consistent with those of other studies that demonstrate a modest increased risk for stroke associated with alcohol consumption. PMID- 1636185 TI - Effects of cerebral angiomas on perifocal and remote tissue: a multivariate positron emission tomography study. AB - BACKGROUND AND PURPOSE: Using multitracer positron emission tomography, I investigated regional hemodynamic and metabolic changes in both perifocal and remote tissues of cerebral angiomas, with special reference to steal phenomena. METHODS: In 22 patients (14 with arteriovenous malformations and eight with cavernomas) cerebral blood flow, cerebral blood volume, mean vascular transit time, cerebral metabolic rate for oxygen, oxygen extraction fraction, cerebral metabolic rate for glucose, and glucose extraction fraction were measured using standard positron emission tomographic methods. Twelve patients also had their cerebral glucose metabolism assessed during psychophysical activation. Regions of interest representing the angioma, perifocal and remote tissues, contralateral mirror regions, and standard brain regions were analyzed. RESULTS: There were no significant changes in hemodynamic variables or oxygen metabolism in the ipsilateral cerebral hemisphere, but ipsilateral glucose metabolism was reduced both at rest (p less than 0.01) and during activation (p less than 0.05). Glucose (p less than 0.001) and oxygen (p less than 0.001) metabolism in regions of perifocal tissue with low blood flow were decreased, with substrate extraction fractions showing no increase to compensate for insufficient blood flow. Functional recruitment of the cortex overlying the angioma beyond its periphery and supplied by the same arterial branches was subnormal (p less than 0.05) despite relatively unchanged hemodynamics in this tissue compartment. CONCLUSIONS: These data suggest that dysfunction of the cortex supplied by arterial branches also feeding the vascular malformation is related to neuronal deafferentation, while the proportionate decrease in blood flow and metabolism of perifocal tissue may be ascribed to neuronal loss in chronically hypoperfused areas, rather than to persistent hemodynamic steal effects. PMID- 1636186 TI - Combined magnetic resonance imaging and proton magnetic resonance spectroscopy of patients with acute stroke. AB - BACKGROUND AND PURPOSE: The prospect for a therapeutic window for treatment of ischemic stroke encourages the noninvasive investigation of metabolic changes in acute ischemia. Recently, localized proton spectroscopy became available at 1.5-T magnetic resonance systems. In this study we evaluated the usefulness of combined magnetic resonance imaging and spectroscopy on the diagnosis of acute and chronic infarctions. METHODS: Combined magnetic resonance imaging and spectroscopy investigations were carried out with a 1.5-T system in 16 volunteers, eight patients with chronic infarction (greater than 8 months), and 10 patients with acute ischemic stroke (less than 8 hours). We used a stimulated echo sequence to acquire localized spectra from image-guided volumes of interest (16-27 ml). RESULTS: There were no significant interindividual differences of choline, creatine, phosphocreatine, and N-acetyl aspartate resonances in the spectra from volunteers. In chronic infarctions, N-acetyl aspartate was decreased in relation to choline. Acute ischemic infarctions were characterized by decreased N-acetyl aspartate resonances and elevation of lactate. CONCLUSIONS: The study demonstrates the feasibility of proton spectroscopy in stroke patients. Metabolic alterations in ischemic tissue can be monitored and can distinguish acute from chronic lesions. PMID- 1636187 TI - Impairment of endothelium-dependent relaxation in human basilar artery after subarachnoid hemorrhage. AB - BACKGROUND AND PURPOSE: The goal of this study was to determine the alterations in vascular reactivity of human basilar artery after subarachnoid hemorrhage. METHODS: Human basilar arteries were obtained from subjects who died within 1 day after subarachnoid hemorrhage and control subjects who died from causes other than brain involvement. Basilar artery strips were suspended for isometric tension recording in Krebs-Ringer solution. Morphometric study was also carried out on paraffin-embedded sections stained with van Gieson's elastica stain of preselected sites from the basilar arteries. The intimal and medial area and the intimal index ([intimal area/area circumscribed by internal elastic lamina] x 100) were evaluated. RESULTS: Contractile responses to KCl, norepinephrine, and 5 hydroxytryptamine did not differ between subarachnoid hemorrhage and control groups. The endothelium-dependent relaxation responses to thrombin, bradykinin, and calcium ionophore A23187 were less for the subarachnoid hemorrhage group than for the control group. However, the endothelium-independent response to sodium nitroprusside of the subarachnoid hemorrhage group did not differ from that of the control group. Morphometric measurements were comparable between the two groups. CONCLUSIONS: These results suggest that the decreased relaxation responses to thrombin and bradykinin occur at the level of endothelial cells and not smooth muscle cells and that decreased relaxation may be involved in delayed vasospasm after subarachnoid hemorrhage. Although the decreased relaxation was observed within 1 day after subarachnoid hemorrhage, a period in which delayed spasm does not occur, this time difference may be dependent on the severity of bleeding after rupture of an aneurysm. PMID- 1636188 TI - Indomethacin promotes germinal matrix microvessel maturation in the newborn beagle pup. AB - BACKGROUND AND PURPOSE: Although indomethacin has been demonstrated to prevent germinal matrix and intraventricular hemorrhage in clinical and animal studies, the mechanism of action of this agent to prevent hemorrhage remains unclear. Previous studies have demonstrated both that the microvessels in the germinal matrix of newborn beagle pups undergo basement membrane maturation during the first 4 postnatal days and that indomethacin may promote laminin deposition in tumor cell culture systems. METHODS: We employed the newborn beagle pup model to test the hypothesis that indomethacin may stimulate laminin deposition in germinal matrix microvessels. Newborn pups were randomized to receive either 0.1 mg/kg/dose i.p. indomethacin or an equal volume of saline diluent. Pups received doses of study medication once a day for 1, 2, or 3 days and were studied on postnatal days 1, 2, 3, or 4. Pups were anesthetized and systemically perfused with buffered formalin; the brains were removed and prepared for immunohistochemical study. RESULTS: Sections stained with Bandeiraea lectin demonstrated that there was no difference in germinal matrix vessel density among the postnatal ages studied; similarly, there were no differences in vessel density between saline- and indomethacin-treated animals at any postnatal age. Quantification of germinal matrix stained intensity by confocal microscopy demonstrated significant increases in indomethacin-treated pups for both laminin staining at postnatal days 2 (p = 0.05) and 3 (p = 0.0009) and type V collagen staining at postnatal day 2 (p = 0.011). Although staining for beta 1 integrins increased across postnatal ages, there were no differences between saline- and indomethacin-treated animals. CONCLUSIONS: These data suggest that indomethacin may stimulate basement membrane deposition in the germinal matrix microvessels of newborn beagle pups to prevent germinal matrix and/or intraventricular hemorrhage. PMID- 1636189 TI - Time course of cerebral blood flow and histological outcome after focal cerebral ischemia in rats. AB - BACKGROUND AND PURPOSE: The relation between time-dependent changes in cerebral blood flow and the appearance of infarction after focal cerebral ischemia is still a matter for debate. The aim of this study was to measure perfusion after simultaneous occlusions of the left middle cerebral artery and ipsilateral common carotid artery in rats and correlate it with the timing and distribution of histological changes. METHODS: We studied histological and cerebral blood flow changes 5 minutes and 4, 24, and 48 hours after the onset of focal ischemia. Blood flow was determined autoradiographically using [14C]iodoantipyrine. A coronal template subdivided into regions of interest was applied to the autoradiographs and the histological data. RESULTS: In some regions of the nonoccluded hemisphere, cerebral blood flow 5 minutes after occlusion fell below 50% of normal. Many ischemic structures showed stable blood flow for 48 hours after occlusion, confirming that in this model reperfusion is minimal. Infarction occurred eventually in all areas in which blood flow at 5 minutes fell below 10% of that in control rats, but infarction appeared earlier in regions in which blood flow at 5 minutes was below 5% of that in control rats. When blood flow at 5 minutes rose above 12% of that in control rats, the occurrence of infarction became unpredictable. CONCLUSIONS: Despite the general dependence of infarction on perfusion levels, blood flow was not a reliable indicator of those regions committed to infarction. PMID- 1636190 TI - Facilitating postischemic reduction of cerebral lactate in rats. AB - BACKGROUND AND PURPOSE: Dichloroacetate facilitates a decrease in brain lactate during reperfusion after incomplete ischemia. This study examined the possible activation of pyruvate dehydrogenase enzyme by dichloroacetate to explain this effect. Because the duration of ischemia and hyperglycemia exacerbate ischemic brain damage, the effect of both of these factors on lactate reduction with and without dichloroacetate treatment after ischemia also was explored. METHODS: The two-vessel occlusion and controlled blood loss model of stroke was applied to anesthetized rats. Samples of cerebral cortex were analyzed for lactate by enzyme fluorometry and for pyruvate dehydrogenase activity by radioassay. RESULTS: Treatment with dichloroacetate produced no significant stimulation of pyruvate dehydrogenase after ischemia. When the duration of ischemia was increased or 50% glucose was infused before ischemia, brain lactate was significantly higher (p less than 0.01, Duncan's test). After 30 minutes of ischemia, treatment with a low dose of dichloroacetate (25 mg/kg) improved the reduction in lactate (p less than 0.01, Duncan's test). CONCLUSIONS: These results indicate that although dichloroacetate reduces brain lactate after cerebral ischemia, the mechanism of action does not involve dichloroacetate's known ability to stimulate pyruvate dehydrogenase. However, these data support the use of dichloroacetate to lower cerebral lactate, especially in cases where ischemia is greater than or equal to 30 minutes in duration. They also suggest that early restoration and maintenance of perfusion after ischemia and discontinuing the use of 50% glucose before impending ischemia likewise would facilitate reduction of postischemic brain lactate. PMID- 1636191 TI - Early changes in rabbit cerebral artery reactivity after subarachnoid hemorrhage. AB - BACKGROUND AND PURPOSE: Subarachnoid hemorrhage frequently leads to long-term cerebral artery narrowing called vasospasm. Very early changes in cerebral arteries have not been studied extensively and may be critical for the later pathological developments. We therefore determined what changes in the reactivity of cerebral arteries could be observed after 10 minutes' or 24 hours' contact with subarachnoid blood. METHODS: Ten minutes or 24 hours after the injection of blood or physiological solution (sham hemorrhage) into the cisterna magna of anesthetized rabbits or no injection (control rabbits), segments of the middle cerebral, basilar, and vertebral arteries were removed for conventional in vitro tension measurements. Concentration-response curves to four endogenous constrictors likely to be released after hemorrhage were obtained, and the maximum relaxation to acetylcholine was determined. RESULTS: There were no significant differences between the sham hemorrhage and control groups. Compared with control rabbits, treated animals showed increased reactivity to uridine triphosphate in the basilar and vertebral arteries at 10 minutes but not at 24 hours, whereas reactivity was increased in the middle cerebral artery only at 24 hours. Reactivity to serotonin was greatly increased in all arteries at both latencies (up to 2.7 times). Reactivity to noradrenaline was unchanged in the basilar and vertebral arteries at 10 minutes; reactivity in both the basilar and middle cerebral arteries was increased at 24 hours, which is compatible with denervation supersensitivity. There were only minor changes in the reactivity to histamine, and only at 10 minutes. Relaxation to acetylcholine was increased for the middle cerebral artery at 10 minutes but otherwise was not significantly changed. CONCLUSIONS: Reactivity to uridine triphosphate, serotonin, and noradrenaline greatly increases by 10 minutes to 24 hours after subarachnoid hemorrhage, and this increase is not owing to the mechanical effects of intracranial hypertension, nor is it related to impaired endothelium-dependent relaxation. It is suggested that these and other spasmogens cause excessive muscular calcium loading with a very rapid onset after subarachnoid hemorrhage. PMID- 1636192 TI - A phospholipase C inhibitor ameliorates postischemic neuronal damage in rats. AB - BACKGROUND AND PURPOSE: The hypothesis of calcium-induced neuronal damage has been proposed regarding brain ischemia. Phospholipase C is an enzyme that catalyzes the phosphodiesteratic cleavage of phosphatidylinositol. The cleavage of phosphatidylinositol 4,5-bisphosphate by phospholipase C yields 1,4,5-inositol triphosphate, which mediates intracellular release of calcium, and 1,2 diacylglycerol, which is an activator of protein kinase C. We examined the effect of phenylmethylsulfonyl fluoride, a phospholipase C inhibitor, on delayed neuronal damage after transient forebrain ischemia in the hippocampal CA1 subfield in rats to assess the role of phospholipase C in postischemic neuronal damage. METHODS: Twenty-minute forebrain ischemia was induced using the method of Pulsinelli and Brierley. We measured the neuronal density of the hippocampal CA1 subfield 7 days after reperfusion. The effect of phenylmethylsulfonyl fluoride was tested in both pretreatment and posttreatment groups. RESULTS: In the vehicle treatment group (n = 13), neuronal density was 51 +/- 42/mm (mean +/- SD). The neuronal densities in the 50-mg/kg (n = 12) and 100-mg/kg (n = 14) phenylmethylsulfonyl fluoride pretreatment groups and the 100-mg/kg (n = 10) phenylmethylsulfonyl fluoride posttreatment group were 99 +/- 50, 150 +/- 55, and 143 +/- 63/mm, respectively. These values were significantly higher than that of the vehicle treatment group (p less than 0.05, p less than 0.01, and p less than 0.01, respectively). CONCLUSIONS: It is suggested that the activation of phospholipase C has an important role in postischemic delayed neuronal damage. PMID- 1636193 TI - Reduction of infarct volume and mortality by thrombolysis in a rat embolic stroke model. AB - BACKGROUND AND PURPOSE: Thrombolytic therapy with recombinant tissue plasminogen activator was tested in a rat embolic stroke model. METHODS: The rat carotid territory was embolized with arterial-like microthrombi formed under pressure. Hemispheric cerebral blood flow before and after embolization was measured by the intraarterial Xenon-133 injection method. Fifteen minutes after embolization, 24 rats were treated with 3 mg/kg or 10 mg/kg tissue plasminogen activator, and 27 were treated with saline. Carotid angiography displayed the rate of occlusion of the cerebral arterial supply before and after treatment. Brains were fixed and evaluated neuropathologically and infarct volume was measured. RESULTS: Cerebral blood flow was reduced 70-86% after embolization. The comparison of pretreatment and posttreatment angiography showed significant (p = 0.0005) reperfusion in the treated rats. Thrombolytic therapy significantly reduced the infarct volume from 55.1% to 24.4% of embolized hemisphere volume (p = 0.007) and increased the survival rate from 0.48 to 0.96 (p = 0.0004). Fifty-three percent of the embolized rats recanalized completely after thrombolytic treatment and developed almost no infarction (median volume 2.8%), and all survived. No hemorrhagic complications were observed. CONCLUSIONS: Early thrombolytic therapy induced recanalization and reduced mortality and infarct volume after embolic stroke in this model. PMID- 1636194 TI - Fatal basilar vasculopathy complicating bacterial meningitis. AB - BACKGROUND: Bacterial meningitis complicated by thrombosis, vasculitis, and aneurysm formation affecting both small and distal branches of cerebral vessels has been well described. Involvement of major cerebral vessels is rare and has only been documented late in the course of disease. CASE DESCRIPTION: We describe the clinical and pathological findings in a young man who presented with pontine infarction as an early manifestation of bacterial meningitis. Streptococcus milleri, an unusual organism in this setting, was cultured. Despite improvement with antibiotic therapy, the patient experienced fatal subarachnoid hemorrhage. A ruptured inflammatory aneurysm of the basilar artery, evidence of residual meningitis and vasculitis, and basilar thrombosis associated with pontine infarction were found. CONCLUSIONS: Bacterial meningitis, which may be associated with severe vasculopathy of the basilar artery and lead to cerebral infarction, aneurysm formation, and subarachnoid hemorrhage, should be considered in the differential diagnosis of these conditions. The role of S. milleri in meningitis and its vascular complications merits further study. PMID- 1636195 TI - Loss of vision induced by the color white: a sign of carotid occlusive disease. PMID- 1636196 TI - Technology used to assess vasomotor reactivity affects results. PMID- 1636197 TI - Neurocysticercosis as a cause of stroke. PMID- 1636198 TI - Thrombin activity in cerebrospinal fluid after subarachnoid hemorrhage. PMID- 1636199 TI - Sneddon's syndrome and antiphospholipid antibodies: clarification of a controversy by skin biopsy? PMID- 1636200 TI - Special issue: AIDS. PMID- 1636201 TI - The OSHA bloodborne pathogens standard. AB - 1. The OSHA Standard is intended to reduce the risks to health-care workers of exposure to bloodborne pathogens. Because the patient's HIV or HBV status is often unknown, the Standard focuses on reducing the risks of exposure to blood and those body fluids to which universal precautions apply. 2. Engineering and work practice controls to reduce the risk of exposure include techniques for handling, cleaning, and decontaminating instruments with minimal hand contact; using containers to pass surgical instruments; wearing puncture-resistant gloves; and using forceps or clamps to remove scalpel blades from knife handles. 3. Employers must provide personal protective equipment at no cost. This equipment must prevent blood or other potentially hazardous materials from passing through or reaching employee's work or street clothes, skin, eyes, mouth, or other mucous membranes during normal conditions for the duration of time used. PMID- 1636202 TI - Intervention in early HIV infection. AB - 1. The primary goals of early intervention in HIV infection are to prevent or delay disease progression and to interrupt HIV transmission. 2. After assessing the stage of a patient's infection, the next goal of early intervention is to minimize the risk of progression. The initial assessment of an HIV-infected individual should include a comprehensive evaluation of all previous disease exposures that might become problematic with immune system compromise. 3. Two antiviral agents are licensed to treat HIV infection: zidovudine and didanosine. Only zidovudine is approved for treatment of early HIV infection and is recommended for all HIV-positive adults with or without symptoms of disease progression who have absolute CD4 helper cell counts less than 500. PMID- 1636203 TI - Women and the AIDS epidemic: no longer hidden. AB - 1. Women acquire HIV infection along one of three routes: parenteral, sexual, or vertical (perinatal). The HIV/AIDS epidemic among women in the US is growing primarily through parenteral and heterosexual exposures, which are tightly linked to social issues of substance abuse. 2. The majority of AIDS clinical trial participants have been white men. Differences in male and female physiology, hormonal influences on drug pharmacokinetics, and the social context of disease may render protocols ineffective or even harmful for women. 3. To respond effectively to the AIDS epidemic among women in the US, major public health issues, such as access to care, availability of family planning and drug treatment services, and racial discrimination, must be addressed. PMID- 1636204 TI - The child with HIV infection. AB - 1. Although incurable, HIV infection is treatable. Advances in antiretroviral therapy, prophylaxis to prevent opportunistic infections, treatment of opportunistic infections, and aggressive nutritional intervention allow for prolonged survival with a reasonable quality of life for many infected children. 2. HIV-infected children tolerate the majority of surgical procedures well; HIV infection alone is not a contraindication to surgery. Because of the multiple laboratory abnormalities that occur in children with HIV, nurses must assess that the appropriate laboratory testing has been completed and that the results have been reviewed. 3. Symptoms in children with HIV result from multiple causes and present in a variety of ways. As the lives of children are extended with better supportive and antiviral treatment, additional manifestations of HIV are being noted. PMID- 1636205 TI - Update on AIDS: the second decade. PMID- 1636206 TI - AIDS: an equalizer among the races. PMID- 1636208 TI - Package simplifies compliance with federal regulations. PMID- 1636207 TI - Consumer advisory on AIDS available to patients. PMID- 1636209 TI - HIV insurance plan for health-care workers provides lifestyle coverage. PMID- 1636210 TI - Blood exposure and puncture risks for OR personnel. AB - 1. Although all health-care workers are at risk for exposure to bloodborne organisms, OR personnel are the most intensively exposed to blood. Exposures to blood were noted in up to half of the procedures observed. 2. Risk-reduction strategies include using two pairs of puncture-resistant gloves and face protection for all procedures; wearing impermeable gowns during procedures with heavy blood loss; using surgical instruments and techniques that reduce the chance of percutaneous contacts; and adopting protocols for handling sharps, counting sponges, and cleaning the operating room. 3. Better and more comfortable personal protective equipment is needed. Manufacturers should develop risk protective and cost-effective barriers that reduce risks for patients of surgical wound infections while reducing the risks for health-care workers of exposures to blood and bloodborne pathogens. PMID- 1636211 TI - [Changes in the form and ultrastructure of the smooth-muscle cells in the human aorta in prenatal ontogeny]. AB - The shape of smooth muscle cells (SMC) was analysed using the phase contrast microscopy of cell suspensions obtained by alcohol-alkali dissociation, as well as the semithin sections prepared in perpendicular planes. The phenotype of SMC was analysed using transmission electron microscopy. The shape of SMC changes from preferentially round to preferentially spindle-like and stellate one during development. The differentiation of SMC is accompanied with the increase in the contractile apparatus content and in the decrease in the content of synthetic organelles. PMID- 1636212 TI - [The intracellular pH and cell proliferation of the LS cell line and its derivative LSM adapted to monolayer growth]. AB - The dynamics of intracellular pH (pHi) during proliferation of cells of LS line in bicarbonate-containing media and of its derivative LSM line adapted to grow in a monolayer has been studied. The contact of LS cells with a solid substrate was not accompanied by their spreading and by an increase in pHi. The pHi values of growing and resting LS cells were practically equal (7.03 and 6.97, respectively). The adhesion and spreading of LSM cells were accompanied by an increase in pHi. The proliferation of LSM cells occurred at different pHi values: at 7.32 on solid substrate with serum, at 7.18 on substrate without serum, at 7.13 in a serum-containing suspension, at 6.97 in a suspension without serum. The highest growth rate was observed at the increased pHi value. Cell proliferation on the substrate stopped at pHi values within 7.10 and 7.13 which were equal to or exceeded the pHi of growing cells in suspension. No difference was observed between LS and LSM cells in the activities of Na+/H+ exchange and transport of Cl into cells that are involved in pHi regulation. Transport of HCO3- into the cytoplasm of LSM cells was more active than that of LS cells. The role of pHi in the anchorage dependence of cell proliferation is discussed. PMID- 1636213 TI - [The effect of the synthetic leu-enkephalin analog dalargin on the proliferative activity of glioma C6 cells and on the intensity of their DNA synthesis]. AB - Effect of dalargin, an opioid peptide (a synthetic analogue of Leu-enkephalin), on proliferation and intensity of DNA synthesis of C6 glioma cells was studied. Specific conditions of cultivation were selected, with a low control value of proliferation, which permitted to assess growth-stimulating effect of the peptide. Growth curves were plotted to assess peptide activity, which demonstrated that reaction was a many-phase process: a significant increase in cell number under peptide effect was observed only at the beginning of the logarithm phase and at the beginning of the prestationary phase of the growth curve. Cell number increased on average by 25-27% in the presence of dalargin as compared to control. Reaction of glioma DNA synthesis to dalargin also demonstrates complexity of the process: the peptide changes DNA synthesis, but as a rule, this process has a three-phase character and is not directly associated with the duration of cultivation in the presence of dalargin. Effect of naloxone, an opiate receptor blocker, was analysed to assess the receptor mechanism. It was found that reaction for naloxone and for combined effect of naloxone and dalargin was not the same. PMID- 1636214 TI - [The effect of the functional electrostimulation of rat fast and slow muscles on the structural state of actin in the thin filaments of a ghost muscle fiber]. AB - The effect of electrostimulation of fast (EDL) and slow (SOL) rat muscles on the orientation and mobility of fluorescent probes rhodamine-phalloidine and 1.5 IAEDANS (N-iodoacetyl-N'-(5-sulpho-1-naphtyl)-ethylenediamine), located in various parts of actin molecule, has been studied by polarized microfluorimetry techniques. Muscles were stimulated at 20 Hz with the pulse width of 0.3 msec, some muscles were treated for 6 h during the first day, the other muscles for 6 h a day during the next 4 days before glycerinization. Then muscle fibres freed by the extraction of myosin, tropomyosin and troponin (ghost fibres) were used. It was shown that the binding of myosin subfragment 1 (S1) to actin induced the changes in polarized fluorescence of the fibres. The analysis of the obtained data showed that the formation of actomyosin complex in stimulated muscles resulted in increasing the angle between the thin filaments and the emission dipole of rhodamine-phalloidine, as well as in decreasing the mobility of this dye. In the experiments with the 1.5-IAEDANS label, the angle of the emission dipole decreased, while the label mobility increased. It was suggested that the orientation of domains in actomyosin complex changes following the electrostimulation to affect both the conformational state of F-actin in thin filaments of ghost fibres and actin-myosin interaction. PMID- 1636215 TI - [The expression of hetero-organic antigens of kidney origin on the surfaces of cultured rat hepatocytes under the influence of the narrow-band fractions of non histone chromosomal proteins]. AB - Narrow fractions of nonhistone chromosomal proteins (NHCP) eluted with 0.4-0.5 M NaCl from the phosphocellulose column stimulate expression of hetero-organic antigens of kidney origin on the membrane of intact hepatocytes cultured in suspension. These fractions of NHCP were isolated from the intact rats kidney, from cells of hepatoma 27 and Zajdela hepatoma, and from the carcinogenic liver after a single diethylnirozamine injection. The membrane hetero-organic antigens were identified by means of indirect immunofluorescence using specific immune serum. PMID- 1636216 TI - [The morphology of cell lines suitable for vaccine production studied by scanning electron microscopy]. AB - Five nontumorogenic cell lines suitable for vaccine production were studied by SEM. It was shown that diploid cell line 41 originated from sheep embryo kidney and also two heteroploid cell lines, line 4921 originated from embryo skin and muscles of the African green young monkey and line 4647 from kidney of the adult monkey, maintained normal cell morphology and normal growth pattern in early and in later passages in cultures. Some alterations in epithelial dense monolayer formation were revealed in the heteroploid cell lines: in line 455 originated from spleen of the adult African green monkey, and in line 4184 originated from line 41. The revealed alterations can be considered as the early morphological signs of the transformation of epithelial cells in culture. These cell lines also retained the stability of their morphological characteristics at the earlier and later passages. All the studied cell lines were free of contaminating agents. PMID- 1636217 TI - [Fascicular and sub-fascicular architecture of the cruciate ligament]. AB - The details of the collagen fascicle morphology and the vascularization of the anterior and the posterior cruciate ligament were examined by the combined use of histology, transmission- and scanning electron microscopy, morphometry and immunohistochemistry. The diameters of the collagenous fibrils in the anterior cruciate ligament ranged between 20 and 155 nm (x = 74 nm, s = 18.8 nm) and in the posterior cruciate ligament between 20 and 175 nm (x = 82 nm, s = 25.4 nm). Type III and VI collagen were found distributed throughout the matrix but concentrated in the attachment regions of the ligaments. The content of type IV collagen in the anterior cruciate ligament was low. The amount of arterioles revealed a typical pattern (anterior cruciate ligament: less than 30 years = 2.94/mm2, greater than 90 years = 2.02/mm2, proximal = 3.15/mm2, distal = 2.18/mm2; posterior cruciate ligament: less than 30 years = 4.69/mm2, greater than 90 years = 3.87/mm2, proximal = 4.08/mm2, distal = 3.98/mm2). PMID- 1636218 TI - [Clinical relevance of whole body skeletal scintigraphy in multiple injury and polytrauma patients]. AB - The provision of care to polytraumatised patients is a particular diagnostic and therapeutic challenge. The examination data of 162 polytraumatised patients were retrospectively investigated to determine the diagnostic gain provided by skeletal scintigraphy with 99mTc-HMDP. It was found that every fresh fracture (with the exception of fractures to the skull) led to a scintigraphically clearly demonstrable remodelling reaction within ten to 14 days. The timing of the examination was of decisive importance for the information yield. Not until about the tenth to 12th day did also those fractures that showed a delayed uptake show adequately signal-intensive areas of uptake in the scintigram. Typical examples were additional fractures of the spine and pelvis in patients immobilised by fractures of the limbs. At this time, with the aim of skeletal scintigraphy, an additional fracture was found in half of all patients, and was subsequently verified radiologically. Additional diagnostic information is independent of the ability of the patient to cooperate. This was of particular importance in the case of the very severely injured and old patients. Skeletal scintigraphy can be employed with equal efficacy to reliably exclude bone injuries. Thus, skeletal scintigraphy if of particular significance in the determination of the extent of bone injury in polytraumatised patients. This applies in particular to the preparation of an expertise. Thus, as in the case of staging of malignomas, the additional performance of bone scanning twelve to 14 days after traumatisation should form part of routine care offered to polytraumatised patients. PMID- 1636219 TI - [Fat pad signs and supinator fat line in cubital trauma]. AB - The fat pad sign and the supinator fat line (SFL) are valuable diagnostic aids in the evaluation of bony cubital injuries. A total of 377 lateral X-rays of the elbow joint-including 121 fractures--were investigated. The supinator fat line exhibited bar-like and bird-like configurations in 55.9% and 41.8% of healthy test subjects, respectively. In the presence of a fracture, a wavy configuration, directed downwards from, or running parallel to, the upper edge of the radius, was seen in 95% of the cases. If in the event of an injury to the elbow a wavy configuration is seen in association with a positive anterior and/or posterior fat pad sign, bony involvement of the joint-forming elements may justifiably be suspected. PMID- 1636220 TI - [Traumatic lesions of the proximal tibial epiphysis]. AB - 36 fractures of the tibia involving the proximal tibial epiphyseal cartilage were treated in 35 patients at the Accident Hospital Lorenz Bohler, Vienna over a ten year period from 1980 to 1989. The average age at injury was 13.2 years. Most common concomitant injuries were ruptures of the ACL and/or MCL associated with meniscal lesions in type III- and IV-fractures and fractures of the fibula in type II injuries. We saw two associated aggravating problems as defined by a compartment-syndrome of the lower leg with one immediate peroneal-nerve palsy, but lesion or disruption of the popliteal artery was not observed. 26 patients were treated conservatively and nine patients had to be operated on. Long-term follow-up (means 6.4 years) was available in 28 cases. Premature epiphyseal closure was seen in three cases and one of them developed an axis angulation in the sense of genu recurvatum but operative correction was not necessary. Unsatisfactory results were stated in four cases due to their knee instability or posttraumatic painful arthrosis. There was no case of growth disturbance with axis deformation or angulation requiring surgical revision. PMID- 1636221 TI - [Post-traumatic length discrepancy and muscular atrophy after femoral fractures in childhood]. AB - The results of a clinical follow-up study of 107 children treated in the University Hospital Hamburg-Eppendorf because of femoral shaft fractures are shown. Most of the fractures healed with lengthening of the fractured bone and showed a muscles atrophy of the concerned limb as well. This study demonstrates the connections between these alterations. PMID- 1636222 TI - [Treatment procedure in humeral shaft fractures with primary or secondary radial nerve damage]. AB - We give an account of 28 patients with fractured humerus diaphysis, suffering from primary and seven patients suffering from secondary lesion of the radialis nerve, all treated by operation. In each case the radialis nerve was exposed and the fracture was treated by fixation with compression plates. In case of primary lesions of the radialis nerve, we found intraoperative damages by traction (six times), contusions (seven times), intraneural hamatomas (six times) and for one time perforation of the nerve by bones. The rest of this group (eight times) did not show any pathological finding. Those patients with secondary lesion of the radialis nerve showed damages by traction (three times) and in two cases the nerve was walled up by callus or connective tissue. Two times we could not find any pathological alteration of the nerve. 23 (six) out of 28 (seven) patients with primary (secondary) lesion of the radialis nerve could be followed up. On this occasion we stated complete neurological restitution 20 times (four times) and incomplete restitution three times (two times). The great number of pathological findings, which necessitate operative treatment, the short duration of remission and the high rate of restitution confirm us to leave the way of conservative treatment in cases of primary or secondary lesion of the radialis nerve and the indication of acute operation is given. PMID- 1636223 TI - [The effectiveness of physical therapy techniques. Possibilities of electromyography evaluation]. AB - The purpose of this study is to verify the efficiency of selected physiotherapeutic techniques. EMG analysis with surface electrodes was performed in order to obtain sufficient data about the process of local strain. Furthermore, the local strain of the muscles surrounding a healthy knee is compared with the local strain of muscles after a knee injury (ACL-rupture) with resultant atrophy. The results prove modifications of progress and amplitudes of local strain and of coordination affected by atrophy/non-atrophy. On account of the first results additional research is recommended to investigate the specific aims of the different techniques. PMID- 1636224 TI - [Improved interpretation of intra-operative myelography in dorsal spinal instrumentation]. AB - Intraoperative assessment of the spinal canal during dorsal instrumentation for vertebral fractures which narrow the canal is facilitated by myelography. However, the flow of contrast medium around a displaced fragment may result in an erroneous interpretation of canal patency. By performing myelography prior to instrumentation and reduction of the fracture, a chance in myelography-findings after reduction can clearly be caused only by successful repositioning of the displaced fragment. The possibility of an incorrect interpretation of the investigation can thus be reduced. PMID- 1636225 TI - [Heart arrest as a sequela of clavicular fracture]. AB - After a fracture of the medial part of the clavicle cardiac arrest occurred. This complication can be explained by vagus irritation because of fracture haematoma. The patient survived and was, six months later, of best health. PMID- 1636226 TI - Superficial bladder cancer. PMID- 1636227 TI - Epidemiology and etiology of bladder cancer. AB - Urinary bladder cancer has long been associated with specific etiologic factors, and our knowledge of these factors has increased during this century. The most important factor, even in industrialized societies, is cigarette smoking. Specific chemicals have also been identified as causing bladder cancer, as have a variety of occupational exposures to less well-defined specific agents. In other parts of the world, the association of bladder cancer with Balkan nephropathy, endemic blackfoot disease, and schistosomiasis provides additional leads for investigating, and potentially preventing, the process of carcinogenesis in humans. Many of the critical observations in our understanding of bladder cancer have been made by practicing physicians, and this is likely to continue. It is essential that physicians dealing with bladder cancer patients be attuned to potential etiologic factors, including cigarette smoking, various industrial exposures, or drug exposures to further our understanding of this issue. Bladder cancer is a potentially preventable disease and an important one, as indicated by the total number of cases and the extent of morbidity and death attributable to it around the world. PMID- 1636228 TI - Natural history of superficial bladder cancer. Prognostic features and long-term disease course. AB - Superficial bladder cancer or, more accurately, stages Ta, T1, and Tis encompass a spectrum that ranges from innocuous to life-threatening lesions. There is growing evidence that Ta grade 1 tumors rarely become invasive; although when there is associated carcinoma in situ or severe dysplasia, the risk of invasiveness increases. Carcinoma in situ is treacherous, with unpredictable behavior. Predictors of recurrence and progression are beginning to be identified for the various superficial tumors. PMID- 1636229 TI - Cytologic and histologic features of superficial bladder cancer. AB - Despite technologic advances in diagnostic skills, cytologic and histologic evaluation is still the standard for the identification of bladder cancer, and these two techniques are critical in therapy selection and post-treatment surveillance. The key to the proper interpretation of cytologic specimens lies in appropriate collection and handling of the sample. Because treatment differs according to the histologic type of a tumor, when a mixture of types is found, all should be listed with their relative proportions. Both pathologists and urologists must be aware of the importance of the muscularis mucosae; a transitional-cell carcinoma may invade this layer without extending into the true muscle. PMID- 1636230 TI - Diagnosis and staging of bladder cancer. AB - The need for prompt diagnosis and accurate staging of bladder cancer cannot be over-emphasized, as delays in diagnosing the tumor are clearly associated with a poor prognosis. Accurate staging using the American Joint Committee system is essential if clinicians are to compare the results of different therapies. PMID- 1636231 TI - Surgical techniques for endoscopic resection of bladder cancer. AB - Accompanying the advances in surgical techniques and new intravesical and systemic therapeutic agents for the treatment of individuals with bladder cancer has been the development of greatly improved instrumentation for viewing the interior of the urinary tract and removing neoplasms. Fiberoptic lenses can now be combined with a video system, which enables the urologist to examine the lower urinary tract, not only more easily but with greater magnification. Training is obviously accelerated with the use of video endoscopy. The system also provides the opportunity for documentation and transmittal of the operative findings using either still or motion photography. The endoscopic procedure should be carried out in an orderly fashion. Sufficient lenses and cautery loops must be available to visualize the entire lower urinary tract and to biopsy or resect any abnormality and ensure hemostasis. The urologist should work closely with the pathologist to obtain sufficient cytologic and pathologic material to be confident of the presence or absence of tumor. PMID- 1636232 TI - Laser surgery for transitional-cell carcinoma. Technique, advantages, and limitations. AB - Lasers generate a unique form of energy with specific tissue effects different from those of either unipolar or bipolar electrocautery. A noncontact coagulation necrosis of superficial transitional-cell carcinoma of the bladder can be achieved. There are insufficient data to support the contention that the recurrence rate of transitional-cell carcinoma is decreased by laser therapy. However, there is abundant evidence that laser treatment of superficial bladder cancer is effective in eradicating grossly visible tumors. Bleeding does not occur during laser application, a clear advantage over electrocautery resection. Additionally, the treatment can sometimes be performed without anesthesia, and the energy can be transmitted via flexible fibers, facilitating the use of flexible cystoscopes. Bladder perforation is unlikely, obturator nerve stimulation does not occur, and postoperative Foley catheter drainage of the bladder is unnecessary. Tumors within bladder diverticula can be treated endoscopically with lasers, and stenosis of the ureteral orifice is rare. There is experimental evidence that laser treatment does not increase the absorption of intravesical chemotherapy, possibly allowing earlier adjuvant use of intravesical treatment postoperatively. On the other hand, there are limitations of laser treatment. Lasers are less familiar to both surgeons and operating room personnel. Appropriate eye protection during treatment is mandatory. Tumor staging is suboptimal, because tissue from the base of the lesion is not routinely available for histologic examination. Accordingly, appropriate patient selection is a paramount consideration. Finally, bowel injury without bladder perforation is a unique, though rare, complication of laser surgery. Simultaneous laparoscopy may be of benefit in some patients but is not indicated routinely. Although laser treatment has not revolutionized the management of superficial bladder cancer, it has an established and enduring role. Future changes in surgical instruments seem likely to increase the usefulness of lasers in managing patients with transitional-cell carcinoma of the bladder. PMID- 1636233 TI - Recurrent or aggressive bladder cancer. Indications for adjuvant intravesical therapy. AB - Advances in understanding of the variables that adversely affect the prognosis of patients with superficial bladder cancer allow more accurate predictions of the aggressive biologic potential of tumors. Intravesical therapy appears to be an effective and essential adjuvant in those patients with high-risk tumor variables. Multiple risk factors related to the tumor, individual patient characteristics, and treatment modality must be evaluated. Assignment of the relative importance of these risk factors will differ from patient to patient. Factors useful for predicting tumor aggressiveness in order to decide the appropriateness of adjuvant intravesical therapy include tumor size, configuration, and grade; ploidy status; Tis and T1 categories; multifocality; postoperative cytologic analysis; the failure of prior intravesical therapy; and prostatic urethral involvement. The integration of this information with formulation of a treatment plan represents both the art and the science of urologic oncologic practice. Research efforts need to be directed at the development of better tumor markers for superficial bladder cancer. PMID- 1636234 TI - Carcinoma in situ. AB - Carcinoma in situ is a high-grade and aggressive manifestation of transitional cell carcinoma of the bladder that has a highly variable course. The treatment of CIS has undergone dramatic changes since this malignancy was first recognized. While cystectomy was once recommended as the initial treatment of choice, recognition of the highly variable prognosis and the uniformly high response rate to intravesical BCG has prompted a more conservative approach to management. While it is recommended that patients be offered the option of radical cystectomy, data do not currently exist to confirm that cystectomy provides a superior survival or quality of life compared with an initial trial of BCG immunotherapy followed by salvage cystectomy if needed. With current optimal BCG immunotherapy regimens, which consist of a 6-week course of BCG followed by three weekly instillations at 3 months, 6 months, and every 6 months for 3 years, the complete response rate is 82%; and it is estimated that more than 75% of patients having a complete response will remain continuously disease free for 5 or more years. Patients who fail BCG immunotherapy without evidence of progression may yet be candidates for intravesical chemotherapy, photodynamic therapy, or alternative immunotherapies such as alpha-2b interferon, bropirimine, or keyhole limpet hemocyanin. PMID- 1636235 TI - Principles of intravesical chemotherapy and immunotherapy. AB - By tailoring the use and selection of an intravesical agent to the individual patient, it should be possible to reduce toxicity and avoid overtreatment. Similarly, patients with more alarming disease processes can be treated sooner if the need for that more aggressive or toxic therapy is recognized early. Finally, it is important to recognize that patients who fail initial therapy with BCG have a good probability of responding to additional BCG and that there are promising investigational immunotherapies available for those who fail adequate courses of BCG. PMID- 1636236 TI - Intravesical chemotherapy. Treatment selection, techniques, and results. AB - A variety of chemotherapeutic agents are available for the patient with rapidly recurring superficial bladder cancer. Management should have two therapeutic goals--ablation of existing tumors and prevention of tumor recurrence. Stage, grade, and multicentricity are all important factors in the decision for therapeutic intervention. Intravesical instillation of chemotherapeutic agents can reduce the rate of recurrence of superficial tumors but has not yet been proved to lower the incidence of later muscle-invasive tumors. Different dosage schedules and methods require further study. Empiric dose schedules may not provide optimal therapeutic effects. The question of timing of instillation of agents after definitive resection needs clarification as well. Questions that remain can be answered only through appropriately designed studies encompassing large numbers of patients with treatments assigned in a randomized fashion. PMID- 1636237 TI - Complications of intravesical chemotherapy. AB - A variety of intravesical chemotherapeutic agents are now available for the treatment of superficial transitional-cell carcinoma of the bladder. The toxicities associated with these agents may make one more appealing than another in the face of similar efficacies. Intravesical instillations of thiotepa have resulted in incidences of leukopenia of 8% to 54%, of thrombocytopenia of 3% to 31%, and of irritative voiding symptoms of 12% to 69%. Close monitoring of blood counts prior to weekly instillations remains vital in preventing myelosuppressive complications. The complications associated with the intravesical use of mitomycin C are mainly chemical cystitis and contact dermatitis. Additionally, allergic reactions have been documented. Most of these complications respond to cessation of therapy with application of topical steroids as needed. Complications of reduced bladder capacity, bladder-wall calcifications, and myelosuppression are uncommon. Toxicities associated with the use of doxorubicin, epirubicin, and ethoglucid are almost exclusively local and usually described as mild to moderate dysuria, frequency, or urgency. Case reports of systemic reactions to doxorubicin are notable in that the patients responded well to diphenhydramine and, in one severe case, epinephrine. Other adverse effects such as reduced bladder capacity, fever, and nausea and vomiting are very uncommon. New agents, such as mitoxantrone, are undergoing phase I and phase II studies. The ideal agent, which would be highly effective and minimally toxic, remains to be developed. PMID- 1636238 TI - Immunology of the bladder. AB - Immunobiology techniques that once were the domain of research are increasingly being applied in the clinic. Transitional epithelium of the bladder undergoes some recognized immunologic changes as it becomes malignant, and their detection may have prognostic value. Examples of such changes are deletion of the ABO(H) blood group antigens, inappropriate expression of Lewis antigens, loss of beta-2 microglobulin and the MHC class 1 heavy chain, and alterations in the production of cellular adhesion molecules and integrins. Other possibly useful markers are ras oncogene products, Thomsen-Friedenreich antigen, epidermal growth factor receptor, and perhaps antigens unique to transitional-cell carcinoma. PMID- 1636239 TI - Bacillus Calmette-Guerin immunotherapy. Techniques and results. AB - Intravesical instillation of bacillus Calmette-Guerin (BCG) has become an important adjunct in the management of patients with stages Ta and T1 transitional-cell carcinoma of the bladder and carcinoma in situ (CIS). For BCG to be effective, patients should be assigned to the appropriate protocol. With proper treatment, tumor recurrences can be prevented in as many as 80% of patients, residual tumor eradicated in 60%, and CIS eliminated in 70% of appropriately selected patients. PMID- 1636240 TI - Complications of bacillus Calmette-Guerin immunotherapy. AB - Knowing when to give and when to withhold BCG will prevent most complications, but even when all precautions are taken, some complications will occur. The initial step in the treatment of infectious complications is the use of isoniazid. Routine prophylactic isoniazid should not be given, as animal studies have confirmed that immune stimulation, and presumably antitumor activity, can be inhibited by isoniazid prophylaxis. However, when cystitis persists more than 2 days or is so severe that it does not respond to symptomatic treatment, isoniazid 300 mg daily is used to control the symptoms, prevent progressive infection, and avoid the overgrowth of BCG, which can result in excessive organisms and suppression of the immune response. If symptoms progress despite isoniazid treatment or do not begin to abate within 1 to 2 weeks, rifampicin 600 mg daily is added. Rifampicin is given from the beginning in patients with potentially severe extravesical BCG infection such as pneumonitis, hepatitis, or nephritis. In patients with symptoms such as fever, malaise, or bladder irritation that respond within a few days, it generally is necessary to continue antitubercular antibiotics for only 2 weeks. Those with extravesical infection and those who do not respond promptly to treatment are treated for 3 months, and those with severe or deep-seated infection are treated for 6 months. The current recommendation for the treatment of sepsis after BCG administration, based on limited clinical experience and controlled animal experimentation, is to use isoniazid and rifampicin plus prednisolone 40 mg daily.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636241 TI - Long-term results of intravesical therapy for superficial bladder cancer. AB - Intravesical chemotherapy will cause complete regression of existing papillary tumor in one third to one half of patients. Controlled clinical trials have demonstrated that chemotherapy reduces the short-term incidence of tumor recurrence by 15% to 18%, but by 5 years, the number of patients suffering tumor recurrence is equal to that in patients treated with surgery alone. Tumor progression cannot occur in the absence of tumor recurrence, but existing studies of intravesical chemotherapy have failed to demonstrate significant reduction in disease progression or mortality rate with treatment. Immunotherapy has the advantage of a mechanism of action different from that of cytotoxic chemotherapy. Immunotherapy with BCG has resulted in complete tumor regression in one half or more of treated patients with papillary tumors and in more than 70% of those with CIS. Controlled studies similarly demonstrate a significant reduction in tumor recurrence, and protection from tumor recurrence has been observed to persist for 5 years or more. At the present time, data remain limited, but three controlled studies have found statistically significant reductions in the rate of disease progression, and one has found a significant reduction in the mortality rate, with BCG immunotherapy. These observations provide convincing evidence that immunotherapy is the treatment of choice for patients with aggressive superficial tumors and suggest that the development of immunotherapeutic alternatives to BCG is likely to be rewarding. PMID- 1636242 TI - When intravesical measures fail. Indications for cystectomy in superficial disease. AB - The indications for intravesical therapy for superficial bladder cancer include multifocal or recurrent tumors, lamina propria invasion, CIS, and superficial involvement of the prostatic urethra. Tumor-free success rates approach 70% in most series. Intravesical therapy is usually administered as a 6-week course with a re-evaluation of the bladder at the 3-month interval. If disease persists, a second 6-week course of therapy is administered. If tumor recurs or persists at the 6-month evaluation, treatment is considered to have failed, and another form of therapy is instituted (Fig. 1). In the 30% of patients failing an adequate course of intravesical therapy, cystectomy may be indicated for uncontrollable superficial disease not amenable to transurethral resection, persistent grade III lesions, lamina propria invasion, persistent CIS, persistent involvement of the prostatic urethra, and persistence of tumor in a nonfunctioning bladder. Rarely, cystectomy may be indicated because of severe adverse effects related to intravesical therapy. PMID- 1636243 TI - Continent urinary diversion using an ileal servomechanism sphincter. AB - A continent, catheterizable, physiologically responsive urinary sphincter servomechanism can be created from a short segment of ileum for use in a continent urinary diversion. Because it is easily constructed and provides dynamic continence control, this new sphincter appears to have applications in reconstructive urologic surgery. PMID- 1636244 TI - Autologous rib perichondrial grafts in experimentally induced osteochondral lesions in the sheep-knee joint: morphological results. AB - The purpose of the present study was to examine the fate of autologous perichondrial grafts after transplantation into cartilage lesions in weight bearing joints. Osteochondral lesions were made in the articular surface of knee joints in 36 sheep. The defects were filled with autologous rib perichondrial grafts which were secured by either collagen sponges (12 animals) or fibrin glue (12 animals). Defects without perichondrial grafts served as controls (12 animals). Following 1 week of immobilization of the operated leg, the plaster was removed and the animals were allowed to move freely. Animals were sacrificed after 4, 8, 12 and 16 weeks. The grafts were removed and investigated histologically. In contrast to weight-bearing areas and control defects, hyaline like cartilage formation was seen in non-weight-bearing areas after 4 weeks. This newly formed cartilage revealed strong metachromasia following staining with acidic toluidine blue and reacted positively with periodic acid-Schiff, indicating de novo synthesis of proteoglycans and glycoproteins. Scanning electron microscopy and examinations with polarized light confirmed a hyaline cartilage-like architecture for the surface area as well as for the fibre orientation of the whole graft. Enzyme histochemistry for alkaline and acid phosphatase activity showed positive reactivity only at the base of the transplants. PMID- 1636245 TI - Adrenal tumours in Chinese. AB - Patients with adrenal tumours were identified (n = 412). Among them, 43% (176 patients) had primary and 57% (236 patients) had secondary tumours. Of the primary tumours, 71% were adenomas, but adrenal cortical carcinoma 6.8% (12 cases), phaeochromocytoma 9.7% (17 cases), neuroblastoma 6.2% (11 cases), ganglioneuroma 1.1% (2 cases) and myelolipoma 4% (7 cases) were also seen. Rare tumours like lipoma and haemangioma were also found. Most of the metastatic tumours were carcinomas (88.2%), mainly from lung (33.2%), stomach (15.9%) and oesophagus (17.3%). PMID- 1636246 TI - Differentiated thyroid carcinomas: the relevance of various pathological features for tumour classification and prediction of tumour progress. AB - In this series of 263 surgically treated cases of thyroid cancer, 12% were finally classified as benign lesions after histopathological review. Difficulty in the assessment of tumour capsule invasion in follicular neoplasms was the most frequent cause of diagnostic error. Squamous metaplasia, clusters of ground glass nuclei and psammoma bodies were found to be the most specific discriminators between papillary and follicular carcinomas. Among papillary carcinomas, tumour diameter above 30 mm, thyroid capsular invasion and regional lymph node metastases were found to be significant prognostic factors according to survival analyses. Of additional practical importance, our results indicate that tumour infiltration in the thyroid capsule should be reported as a marker of early extra thyroidal extension. PMID- 1636247 TI - Macrophages in normal human bone marrow and in chronic myeloproliferative disorders: an immunohistochemical and morphometric study by a new monoclonal antibody (PG-M1) on trephine biopsies. AB - An immunohistochemical and morphometric study was performed on routinely processed trephine biopsies of the bone marrow in 30 normal individuals and in 90 patients with various subtypes of chronic myeloproliferative disorder. Using a new monoclonal antibody (PG-M1) directed against a formalin-resistant epitope on macrophages and by employment of the Prussian blue reaction, quantitation of this cell population was feasible. Morphometric analysis revealed that the number of iron-laden macrophages represented only a fraction of the total number of histiocytic reticular cells. As could be expected, in polycythaemia rubra vera, no haemosiderin deposits were detectable, but the content of macrophages slightly exceeded that of the normal bone marrow. In chronic myeloid leukaemia 9 of 30 patients showed a significant increase in PG-M1-positive reticular cell elements. These were consistent with pseudo-Gaucher cells, sea-blue histiocytes and intermediate cell types. Primary (idiopathic) myelofibrosis-osteomyelosclerosis was characterized by a significant increase in macrophages (25 of 30 patients). Involvement of macrophages in the complex mechanisms generating bone marrow fibrosis and angiogenesis and in bone remodelling (osteosclerosis) may be responsible for this finding. PMID- 1636248 TI - Microscopic features of the regeneration of white pulp in autotransplanted spleens in rats. AB - The process of regeneration of white pulp in autotransplanted splenic tissue, implanted into a pocket made by the greater omentum in rats, was investigated histologically and immunohistochemically. Three days after transplantation, almost all implants were necrotic. At day 7, viable splenic tissue had gradually regenerated at the periphery of the implants. At day 10, lymphocytes accumulated around the arterioles. The accumulations resembled the periarteriolar lymphoid sheath of normal spleens in structure, but consisted mainly of B-lymphocytes, with a few scattered T-lymphocytes. However, by week 2, the localization peculiar to T- and B-lymphocytes became definite, and follicular dendritic cells were simultaneously observed in the lymph follicles. This regeneration of the white pulp in the autotransplanted spleens differed from the formation of the white pulp during ontogeny and during recovery after spleen irradiation. PMID- 1636249 TI - Chromosome analyses in patients with myelodysplastic syndromes: correlation with bone marrow histopathology and prognostic significance. AB - Chromosome analyses of bone marrow and peripheral blood cells were performed in a total of 51 patients with myelodysplastic syndromes (MDS) simultaneously with histopathological examination of resin-embedded bone marrow biopsies. Diagnosis of MDS was established by histopathology according to the French-American-British (FAB) classification, and reassessed by haematological data and clinical course. Clonal karyotypic changes were found in 30 of the 51 patients (59%): in 15 of 19 (79%) patients with refractory anaemia, 7 of 11 (64%) with refractory anaemia and excess of blasts (RAEB), 6 of 10 (60%) with RAEB in transformation, and 2 of 11 (18%) with chronic myelomonocytic leukaemia. The following three features of the histopathology revealed positive correlations with karyotype abnormalities: all cases of myelofibrosis in MDS (7/51) were accompanied by chromosome aberrations, microforms of megakaryocytes with reduced nuclear lobulation were observed in 18 of 30 cases with karyotype changes, and hypocellularity of haematopoiesis was associated with aberrations of chromosome 7 in 2 of 4 cases. No positive correlations were revealed between abnormal karyotypes and the transformation to acute leukaemia. The survival times were significantly decreased in patients with complex (3 and more) karyotype changes, when compared with patients with single (1-2) chromosome aberrations or normal karyotype, independently of the FAB classification. PMID- 1636250 TI - Vascular and myofibrillar lesions in acute myoglobinuria associated with carnitine-palmityl-transferase deficiency. AB - A case of severe exercise-induced myoglobinuria in a 14-year-old boy suffering from a carnitine-palmityl-transferase (CPT) defect is reported. Biopsies of the forearm muscle were examined using light and electron microscopy in the acute and recovery phases of the illness. The first biopsy showed the presence of scattered foci of necrosis where necrotic fibres with occasional disruptions of the basal lamina were seen around injured capillaries. Various degrees of damage and different stages of evolution were found in these foci, which also contained regenerating muscle fibres. In the second biopsy, performed 2 weeks later, most of the fibres displayed a normal structure. Necrosis was no longer present. However, in some areas perivascular fibrosis was prominent, the fibres were small and irregularly shaped, and their nuclei often centrally located. These data strongly suggest that circulatory disorders and ischaemia, brought about by premature acute metabolic imbalance, could be involved in the development of exercise-induced myolysis observed in CPT deficiency. The risk of fibrous cardiomyopathy in these patients is pointed out. PMID- 1636251 TI - The features of glomerulitis in the acute stage of panarteritis nodosa. Developmental process of glomerulitis and correlation between glomerular and vascular lesions. AB - In order to determine the morphological characteristics of certain vascular and glomerular lesions and the correlation between them, we attempted three dimensional observation using serial sections of an autopsy kidney, from a patient with panarteritis nodosa in the acute phase. Fibrinoid necrotizing vasculitis spread from arcuate arteries to arterioles in a segmental, eccentric pattern, especially occurring at bifurcations. Segmental arteriolitis often originated in extraglomerular capsular arteriole and spread into the intraglomerular capsular arteriole and glomerular capillaries, directly leading to necrotizing glomerulitis. Some of the glomerulitis connected directly with extracapsular arteriolitis was segmental and eccentric in distribution. Most of the glomerulitis had a tendency to originate in the hilar arteriole, which was near bifurcations between the arteriole and glomerular capillaries. Segmental glomerulitis was found to consist of four elements: glomerular tuft necrosis with fibrin exudation, crescents, rupture or dissolution of Bowman's capsule, and pericapsulitis. It is suggested that the segmental inflammatory attacks, repeated more than twice, give rise to widespread and almost global necrotizing glomerulitis. PMID- 1636252 TI - Vimentin expression by Reed-Sternberg cells in Hodgkin's disease. AB - The expression of vimentin in Reed-Sternberg cells in 61 samples of Hodgkin's disease (HD) was examined using an avidin-biotin-peroxidase complex technique. Forty biopsies (66%) expressed vimentin, and expression was seen in all subtypes of HD. No immunophenotypic differences between vimentin-positive and vimentin negative cases were noted. The significance of such expression is unclear, but may be related to the alterations in growth and differentiation that are typical of neoplastic cells. PMID- 1636253 TI - Health Care Access Task Force report. Non-financial barriers to care. PMID- 1636254 TI - Practice alert! Immunization initiative. PMID- 1636256 TI - Making research work for you. PMID- 1636255 TI - Doing something about domestic violence. PMID- 1636257 TI - [The long-term behavior of homologous bone transplants in reconstruction of single chamber calcaneus cysts. Conventional and computerized tomography results]. AB - Treatment of four unicameral calcaneal bone cysts by operative packing with homologous trabecular bone grafts was evaluated by conventional radiography and CT after a mean follow-up time of 51 months (range 48-57 months). Data on graft incorporation and remodelling are presented. In all cases trabecular bone showing an orderly arrangement was found to have developed in the cyst space. Homogeneous areas were present in 2 instances. These coincided with the neutral triangle, i.e. a zone in which stresses are physiologically low. Graft incorporation and remodelling followed Wolff's laws of bone transformation and can be regarded as complete before month 27. The final bone pattern is definitely established before month 50. Conventional radiography is sufficient for routinely evaluating the healing pattern. CT should be reserved for research purposes. Impaction of trabecular bone chips may be dispensable. Tight packing without impaction would at least help to save bone graft material. The use of homologous trabecular bone subjected to special pretreatment was found to be unproblematic. It minimizes surgery-related stresses and reduces the operating time. PMID- 1636258 TI - [Intravenous peripheral digital subtraction angiography after stabilization of medial femoral neck fractures. Results and value]. AB - In patients with medial femoral neck fractures the condition of the blood vessels is the decisive factor as to whether or not femoral capital necrosis will develop. Therefore, conventional angiography has been used both preoperatively for the diagnostic work-up and for selecting the best mode of management and postoperatively for prognostic purposes. Its routine use has, however, been limited by the long examination time, the complexity of the technique and the potential complications. Peripheral intravenous digital subtraction angiography (DSA) for imaging peripheral vessels is a far less demanding procedure. Its usefulness was studied postoperatively in 7 patients. The vascular information obtained was inferior to that of conventional angiography because of the inherently poorer vessel imaging qualities. Moreover, since its applicability is limited to patients with a completely intact cardiovascular system and normal cardiac output, it is not suitable for most geriatric patients. It is, therefore, concluded that peripheral intravenous DSA cannot (yet) be recommended as a routine procedure. It remains to be seen whether technical improvements in system features will improve the diagnostic performance. PMID- 1636259 TI - [Spinal internal fixator--analysis of problems in 28 cases]. AB - Problems encountered in the management of thoracolumbar and lumbar spinal fractures with the "fixateur interne" are reviewed. 28 patients were treated between 1986 and 1988. Retrospective analysis identified the following problems: a. Loosening of nuts at the longitudinal rod and/or clamp ends--b. Major corrosion defects of Schanz screws and clamps--c. Large implant volume--d. Non availability of intermediate rod lengths. Earlier problems, i.e. the absence of an effective press-fit (transverse stabilizer) between the 2 longitudinal rods and the non-availability of a cutter for trimming the Schanz screws, have meanwhile been resolved. Loosening of the nuts at the clamp end may cause substantial loss of reduction and jeopardize the outcome of treatment. The problem of how to identify loosening, which is usually recognizable within 27 days, is discussed at length. Since loosening occurs irrespective of fracture type and site, instrumentation length, ancillary surgical procedures, type of postoperative care, preoperative neurological status and operating surgeon, it appears to be inherent in the system. Alterations in neighbouring vertebral segments attributable to rebundant rod lengths cannot altogether be excluded. The potential occurrence of corrosion defects should prompt implant removal after radiologically confirmed fracture healing. PMID- 1636260 TI - [Comparison of manual and mechanical anastomosis technique in operations on the large intestine]. PMID- 1636261 TI - [The human chorionic gonadotropin (hCG) receptor: a new class within the family of GTP protein coupled receptors. Epitope mapping of receptor-bound agonistic and antagonistic forms of hCG]. AB - Human chorionic gonadotropin (hCG) is a member of the glycoprotein hormone family. It is composed of an alpha and a beta subunit, the latter being closely homologous to that of human luteinizing hormone (hLH). HCG and hLH bind to the same receptor. The molecular mass of hCG is 38 kD, up to 30% of which is contributed by the carbohydrate moieties linked to each of the two subunits. Structure-function relationship studies have indicated that both subunits interact with the receptor and that altogether four different peptide domains (two on each subunit) are responsible for high-affinity receptor binding. The carbohydrate units are responsible for expression of agonist activity: deglycosylated hCG (degly-hCG) is unable to induce a biological response (cAMP increase), despite high-affinity binding. We have previously mapped the antigenic surface of hCG and described 14 different epitopes that can be recognized by specific monoclonal antibodies (MCA), i.e. five epitopes on the alpha subunit, five on the beta subunit and four epitopes which are formed through association of the two subunits (conformational or alpha beta epitopes). The number and topography of epitopes was found to be the same on degly-hCG. This framework of immunological coordinates was then applied to probe the orientation of hCG, as well as that of the competitive antagonist degly-hCG in their receptor-bound states. With a receptor-hormone-125I-MCA sandwich approach we found that while hCG still presented two of the 14 epitopes, i.e. beta 3 and beta 5, no epitope was accessible on receptor-bound degly-hCG. This differential pattern thus correlates with the signal transduction-competence of the respective ligand. Overall, these data indicate that most of the surface of hCG is masked by moieties of the receptor. Accordingly, that moiety must itself be folded in a way that it provides a large contact surface. No portion other than the 341-residue long extracellular domain would seem capable of doing that. Computer-assisted secondary structure predictions support this view. This domain is the novel feature that distinguishes glycoprotein-hormone receptors from the other members of the G protein-coupled receptor superfamily. PMID- 1636262 TI - [Importance of locus of control in the disease adjustment process in women with genital cancer]. AB - This study deals with psychological aspects of coping observed in gynecological cancer patients--on the one hand with behavioral, emotional and cognitive reactions to the disease and on the other hand with the efficiency value of these mechanisms in handling the disease. As one important aspect, the attitude towards control of the disease should be correlated with the coping process. Accordingly, the results demonstrate a correlation between high self-responsibility and positive appraisal of the disease: Women who believe they are in control of the disease try harder to fight the disease and interpret their own situation more positively than women with a fatalistic attitude and this enables them to make more sense of the disease; they experience more positive changes in their own lifestyle due to the disease. Furthermore, women who ascribe responsibility for the course of the disease to other interpret their situation in a more positive light. They actively search for social support and obviously experience this trust in the power of other people as a helpful measure. A fatalistic attitude to the disease is combined with rumination and social withdrawal. PMID- 1636263 TI - [Precancerous stages of cervix cancer (CIN)--attitude and coping with the disease]. AB - The subjective reactions and the mental state of 50 patients with a diagnosis CIN I, II and III were studied. The data were gathered after gynaecological follow-up examinations in semistructured interviews and with a list of complaints (B-L) according to Zerssen (1975). Patients with CIN I or II were examined and interviewed 3 months after diagnosis, patients with persistent CIN I or II were studied after 6 months, and patients with CIN III before conization. Patients with CIN reacted to the diagnosis in a similar manner to patients confronted with the diagnosis of cancer. Effective coping with the disease depended on adequate medical information being received by the women. The patients who were satisfied with the medical information had a more positive approach to the course of the disease and found it less life-threatening than those patients who were dissatisfied with the information received. The results of this study indicate that subjective experience of the disease is largely independent of its objective severity. PMID- 1636265 TI - [Thrombophlebitis and ulcus cruris caused by primary varicose veins of the lower extremity. Diagnostic and therapeutic consequences for the general practitioner]. PMID- 1636264 TI - [Clinical aspects and epidemiology of hepatitis B]. PMID- 1636266 TI - [Still's disease in adulthood]. PMID- 1636267 TI - [Medical promotion practices in the 1st half of the 18th century exemplified by Halle]. PMID- 1636268 TI - [Saxony medical development reflected by the royal calendar and state records (1728-1934)]. PMID- 1636269 TI - [Correlation between acinar cell fat accumulation and secretory capacity of the rat pancreas in the early stage of alcohol-induced pancreatopathy]. AB - In patients exhibiting chronic alcohol abuse, the accumulation of fat droplets in pancreatic acinar cells, as well as changes in pancreatic secretion, can be interpreted as early signs of pancreatic damage. Using rats, (the animals were fed for 9 +/- 1 months with a solution of 20% v/v ethanol, combined with either a normal or a fat enhanced diet) we tested whether or not these symptoms are related both to each other and to morphological lesions of the tissue. Based on six separate histological criteria, the lesions were classified into five stages of severity. In order to characterize the secretory capacity of the pancreas, we measured the outputs of lipase, alpha-amylase, trypsin, chymotrypsin, carboxypeptidase A, elastase, and phospholipase A. Compared with the control group, we found that the alcohol-fed animals exhibited a significantly higher degree of morphological damage to the pancreas, as well as an increased frequency of fat accumulation in the acinar cells, and, with the exception of alpha amylase, a rise in the level of enzyme secretion. In the animals exhibiting the highest degree of tissue damage, however, both fat accumulation and hypersecretion appeared to be diminished. This diminution could possibly be interpreted as the first sign of chronic pancreatitis. Increased consumption of fat did not change either the level of fat accumulation in the acinar cells, or the level of pancreatic secretion. Within the group of alcohol-fed rats, the most pronounced levels of hypersection were found in animals exhibiting cellular fat accumulation. However, the secretion levels of the alcohol-fed animals exhibiting no such fat accumulation did not differ significantly from that of the control group. Therefore, a relationship appears to exist in rats between fat accumulation in acinar cells and the level of pancreatic secretion. PMID- 1636270 TI - [The diagnostic value of the amino acid absorption test in detection of a disorder of exocrine pancreatic function]. AB - The amino acid consumption test (AACT) during exogenous stimulation with secretin and CCK was proposed as a sensitive and highly specific test for detection of exocrine pancreatic insufficiency. To further investigate the diagnostic value of this test we measured the AACT in comparison with the pancreolauryl serum test (PLT) in patients with chronic pancreatitis and in patients with gastrointestinal diseases but without pancreatic disease. A total of 48 patients, 23 patients with chronic pancreatitis (CP) and 25 patients with gastrointestinal diseases, were included in the study. Diagnosis of chronic pancreatitis was established by standardized morphological criteria in ultrasound, ERCP, CT, and was confirmed by surgery in 11 cases. The PLT was abnormal in 83% of patients with chronic pancreatitis and normal in 92% of the control subjects (diagnostic accuracy 88%). Basal amino acid concentration was comparable in patients with chronic pancreatitis and in control subjects (300 +/- 12 [symbol: see text] 325 +/- 16 mumol/l). The peak decrease of amino acids occurred after 30 min during combined stimulation with secretin and ceruletide and was not different between the two groups (CP: 11.2 +/- 1.7%, controls: 13.9 +/- 1.9% below basal values). With a 12% decrease of amino acids as cutoff, sensitivity was 74% and specificity 52% (diagnostic accuracy 63%). Integrated amino acid decrease did not show any significant differences between CP and controls (CP: 228 +/- 63% min, controls: 397 +/- 80% min). Determination of the individual amino acids serine, valine, histidine, and isoleucine could also not discriminate between patients with chronic pancreatitis and other gastrointestinal diseases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636271 TI - [An increased incidence of bacterial endocarditis in chronic inflammatory bowel diseases]. AB - Of 92 consecutive patients treated for proven native valve endocarditis three had ulcerative colitis and 2 Crohn's disease. All 5 patients developed severe complications; three had to undergo emergency valve replacement. With a prevalence of 64.1/10(5) cases of inflammatory bowel disease the calculated incidence (5/92) revealed a significant over-representation of inflammatory bowel disease among patients with proven endocarditis (p less than 5.08 x 10(-9)). Possible explanations may be the suppression of cellular immune defense by therapeutic interventions, high frequency of bacteremia caused by increased permeability of the damaged mucosa for bacteria and a higher incidence of diagnostic and therapeutic interventions in this patient population. Therefore, prophylaxis for bacterial endocarditis should be carefully considered before expected bacteremias in patients with highly active inflammatory bowel disease even in the absence of cardiac factors predisposing to bacterial endocarditis. PMID- 1636272 TI - [Experimental damage of the epithelial layer of the ileum by dietary fats: transmission electron microscopy findings and their comparison with cell pathology in Crohn disease]. AB - Regarding the unknown pathogenesis of Crohn's disease repeatedly the importance of diet has been accentuated. Epidemiological, biochemical and animal experimental results have focused on a possible relationship between the consumption of chemically processed, partial hydrogenated fats and the development of regional enteritis. In this context an experimental animal model in pigs was designed to analyze, whether transmission electron microscopic alterations of ileal mucosa could be induced by forage of chemically processed fats. By creation of a retroperistaltic ileal segment the contact time between chyme and intestinal mucosa was prolonged. Our underlying question was to what extent disorders of the intestinal barrier function could be compared to Crohn's disease. Present study concentrates on the epithelial-cell-layer. It was shown that in comparison to the control animals the lamina epithelialis mucosae of all animals after fat-feeding was characterized by: sublethal lesion of the enterocytes/crypt-epithelial cells (shortening and alteration of the microvilli, degeneration of mitochondria, formation of autophagocytic vacuoles); goblet cell hyperplasia and increased production of mucus; focal appearance of intraepithelial lymphocytes as well as presence of polymorphonuclear granulocytes in the epithelium; widening of the intercellular-space locally up to total loss of the functional structure of the epithelial-cell-layer. In total the picture can be evaluated as an inflammatory process of the ileal mucosa. It can be concluded, that chemically processed fats as used in the described experimental conditions could induce this process. The feature of mucosal damage shows obvious similarities to ultrastructural findings in Crohn's disease if compared. PMID- 1636273 TI - Superficial esophageal carcinoma in achalasia, detected by endoscopic surveillance. AB - A 42 year old woman had undergone a Heller myotomy for achalasia of the cardia at age 28. Thereafter, she had become asymptomatic but reported for endoscopic follow-up examinations at three-yearly intervals. Fourteen years after surgery, endoscopy and biopsy revealed "carcinoma in situ" in the proximal esophagus and surgery was recommended. In the resected specimen, a circumscribed area of cancer was demonstrated that invaded the lamina propria but was confined to the mucosa. With the exception of mild and transient postoperative dysphagia, she had an uneventful postoperative course and remains well 16 months following surgery. This case demonstrates that endoscopic surveillance may detect early malignant changes in the achalasic esophagus and may possibly lead to an improvement in survival. PMID- 1636274 TI - [An interesting case--endoscopic hemostasis of an actively bleeding sigmoid diverticulum--a case report]. AB - A pulsating arterial bleeding from a diverticulum, situated in the colon sigmoideum, was identified and stopped during video-documentation in a 70 year old man. After injection with a solution of suprarenin, the diverticulum was turned out like a balloon into the colon and didn't show any signs of further bleeding until the patient was prepared for a semi-elective resection of the sigmoid. This case demonstrates that emergency endoscopy is an effective method for diagnosis and even therapy of massive lower intestinal bleeding which eventually has to be supplemented by radiological techniques like scintigraphy and arteriography. PMID- 1636276 TI - [Esophageal perforation in attempted ERCP]. AB - In this report we refer to a 88-years old female patient who was admitted to our hospital under the diagnosis of cholecysto- and choledocholithiasis. Due to clinical symptoms, general performance status and sonographically proven dilated bile ducts emergency-ERCP was performed by an experienced endoscopist. Unfortunately esophageal perforation occurred due to subsequently diagnosed hiatus hernia. Potential pitfalls during examination as well as a concept of problem management during endoscopies with side-view optics will be discussed. PMID- 1636275 TI - [Side effects of laxatives]. AB - The side effects of anthraquinones, diphenylmethane derivatives (e.g. bisacodyl, sodium picosulphate), saline laxatives, lactulose, and cisapride are discussed. When taken in recommended doses, no relevant side effects have been observed, except for hypermagnesemia following magnesium containing cathartics in renal insufficiency. This holds also true for the time of pregnancy and lactation. (Pseudo-)melanosis coli is characterized by pigment loaded macrophages without apparent functional consequences. It occurs mainly after anthraquinones, but to a lesser degree also after diphenylmethane derivatives. Clinically relevant side effects of the above laxatives have been published exclusively after excessive dosing. They consist in electrolyte disturbances (mainly hypokalemia), metabolic alkalosis, renal tubular dysfunction, and other less frequent side effects. Cases of "cathartic colon" have not been published during the last decades. It was probably due to laxatives which are no longer used. PMID- 1636277 TI - [Pancreatic transplantation: success and problems]. AB - The results of pancreatic transplantation could be improved markedly since using the bladder drainage technique. The best function rates can be achieved when transplanting simultaneously a kidney from the same donor. In our own series of 50 combined pancreas-/kidney transplantations (CPKT) the 1-year-graft function rate for both organs reaches 88%. The drainage of the exocrine pancreatic secretions into the urinary tract leads, however, to a high incidence of recurrent urinary tract infections. Diagnosis of rejections after combined pancreas-/kidney transplantation is mainly based on the function of the simultaneously transplanted kidney and the exocrine secretion of the pancreatic graft. In spite of triple drug therapy (prednisolone, azathioprine, cyclosporine A) and ATG (antithymocyte globulin) prophylaxis the incidence of acute rejection episodes is initially high. For rejection therapy monoclonal antibodies, such as OKT3, are most effective. Glucose metabolism is almost completely normalized after successful pancreatic transplantation. Considering late diabetic complications, however, only positive effects on diabetic neuropathy are confirmed. This is probably due to the very late onset of therapy by pancreatic transplantation. A significant improvement in other late diabetic complications can only be expected in long term follow up studies. The positive effect on physical and psychological rehabilitation, however, improves the quality of life in most of the patients after CPKT substantially. Even though the results of isolated pancreatic transplantation reaches 1-year-graft function rates of approximately 60% in single centers, the indication to this treatment should consider the disadvantages of long term immunosuppression and the uncertain results considering secondary complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636278 TI - [Detection of mutated ras-oncogene in pancreatic cancers: improved diagnostic possibilities using molecular biology techniques?]. AB - C-Ki-ras oncogenes have been detected by polymerase chain reaction in the majority of pancreatic carcinomas. The biological role of ras oncogenes in pancreatic carcinogenesis is unknown. This review summarizes the current knowledge of ras oncogenes in pancreatic carcinomas, the different techniques for oncogenes and their possible diagnostic value. PMID- 1636279 TI - [Acute pancreatitis: bad prognosis for obese patients?]. PMID- 1636280 TI - [Antibodies to neutrophilic granulocytes (p-ANCA): a further indication for a common origin of ulcerative colitis and primary sclerosing cholangitis?]. PMID- 1636281 TI - [Use of endoscopy in gastritis and duodenitis]. PMID- 1636282 TI - [Ombudsman Kristina remains administrator of Radiumhemmet. Interview by Carina Roxstrom]. PMID- 1636283 TI - [Acute care department--successful example with blemishes]. PMID- 1636284 TI - [You can lose money when you get sick during the course]. PMID- 1636285 TI - [Documentation unsatisfactory--many cannot write a record. Interview by Jan Thomasson]. PMID- 1636286 TI - [South African nurses persecuted for professional membership]. PMID- 1636287 TI - [A market economic grasp of health care]. PMID- 1636288 TI - [Models nobody understands]. PMID- 1636289 TI - [District Department Stockholm: one needs competence for models]. PMID- 1636291 TI - [SHSTF acts against racism and hostility toward strangers]. PMID- 1636290 TI - [We must be prepared to risk meeting death. Interview by Maria Ejd]. PMID- 1636292 TI - [Education in medical technology increases safety in nursing]. PMID- 1636294 TI - [Health care education in the background]. PMID- 1636293 TI - [Counseling is a success--Ann-Christine starts a course on the climacteric now. Interview by Eva Aldstedt]. PMID- 1636295 TI - [After half a year in Lebanon--Gunborg and Lotta feel at home in their Palestinian camp. Interview by Kristina Aberg]. PMID- 1636296 TI - [Wage negotiations in the EEC. Can the Swedish model survive?]. PMID- 1636297 TI - [Cornea bank: an increase in the number of transplantations is possible]. PMID- 1636298 TI - [Eye foreign bodies. Patients should be sent to the eye clinic for treatment]. PMID- 1636299 TI - [Eye infections--a red eye can indicate infection]. PMID- 1636300 TI - [Eye prostheses--their production with a more than 100-year old technique]. PMID- 1636301 TI - [Retinal detachment--with microsurgery even severe cases can be cured]. PMID- 1636302 TI - [Testing of hearing aids--the perfect apparatus cannot be found]. PMID- 1636303 TI - [Acoustic trauma--preventive use of hearing protectors]. PMID- 1636304 TI - [Ear infections--how to treat children with ear infections]. PMID- 1636305 TI - [European exchange among permanent laboratory assistants]. PMID- 1636306 TI - [Victims of dislike for foreigners]. PMID- 1636307 TI - [Members in Vasterbotten are disappointed by employers: "Why do we have the lowest salary in the country?"]. PMID- 1636309 TI - [Kitson's model shows the way]. PMID- 1636308 TI - [We manage our own tests with Miran. Interview by Carina Roxstrom]. PMID- 1636310 TI - [Karlskrona helps Klaipeda. A ship comes to Lithuania loaded with health care]. PMID- 1636311 TI - [Eva and Sivan bake cakes for the socially handicapped children]. PMID- 1636312 TI - [Nurses are key persons in child health services]. PMID- 1636313 TI - [Acquitted from indictment of causing death]. PMID- 1636314 TI - [Data system will provide better care and higher wages]. PMID- 1636315 TI - [Madelein goes to Barcelona. Interview by Jan Thomasson]. PMID- 1636316 TI - [A just pension system]. PMID- 1636317 TI - [Now the community takes over primary health care in Ale]. PMID- 1636319 TI - [Treatment of patients the general subject. Interview by Carina Roxstrom]. PMID- 1636318 TI - [Margareta Hallberg (correction of Hallman), nursing instructor and researcher: male dominance is not always oppression]. PMID- 1636320 TI - Molecular biology in diagnostic microbiology. PCR on Mycobacterium leprae. AB - The polymerase chain reaction (PCR) has already produced several hundreds of papers. Alternative procedures for diagnostic purposes based on nucleic acid detection do exist but have until now found less application. Problems with the PCR are discussed. It is proposed that the diagnostic microbiology laboratory has a section devoted to PCR for the diagnosis of diseases whose etiologic agent can "almost not" be cultured such as (for Flanders) Mycoplasma pneumoniae, Chlamydia pneumoniae, Toxoplasma gondii, EB virus and some other agents in particular specimens. In this setting the PCR would only be performed on selected, clinically justified samples, in close collaboration between clinician and microbiologist. PCR will evidently play an important role in research. Illustration is given of PCR applied for the detection Mycobacterium leprae. PMID- 1636321 TI - [The inventors of the obstetric forceps and the obstetric lever]. AB - A multiple lineage is proposed for the invention of the obstetric forceps. Having been conceived by a member of the Chamberlen family in fifteenth- or seventeenth century England, the instrument seems to have been reinvented in Flanders by Jan Palfyn and in Holland by Rogier Roonhuyse. Later, Roonhuyse invented a more effective instrument for coping with the impacted head: the obstetric lever. Palfyn's "Iron Hands" inspired Dusse to produce the "French" forceps which bears his name. PMID- 1636322 TI - New perspectives for the chemotherapy and chemoprophylaxis of AIDS (acquired immune deficiency syndrome). AB - Various new classes of compounds have been recently identified as potent and selective inhibitors of acute HIV infection in vitro. As a rule, these compounds inhibit HIV replication at a concentration of 0.1-1 micrograms/ml, while not being toxic to the host cells at concentrations up to 500 micrograms/ml or higher. Some of the compounds even inhibit HIV replication at a concentration of a few nanograms per ml, thus achieving selectivity indexes up to 100,000, which makes them particularly promising drug candidates for the chemotherapy and prophylaxis of HIV infections in vitro. These new candidate drugs for the treatment of AIDS fall into the following categories: (i) polyanions (polysulfates, polysulfonates, polycarboxylates and polyoxometalates), which interfere with virus attachment to the cell membrane; (ii) some plant lectins and modified (i.e. succinylated) albumins, which may directly interact with the fusion of the viral envelope with the cell membrane; (iii) bicyclam derivatives, which seem to be targeted at the uncoating (disassembly of the viral proteins from the viral RNA genome); and (iv) reverse transcriptase (RT) inhibitors which fall into two subcategories. The phosphonylmethoxyalkyl derivatives PMEA and FPMPA interact, as chain terminators, with the RT substrate binding site, as do azidothymidine (AZT) and the other dideoxynucleoside analogues. The TIBO derivatives and their congeners interact with a non-substrate binding site at the HIV-1 RT, and thus behave as allosteric inhibitors of the enzyme. The TIBO congeners have proved to be highly specific inhibitors of HIV-1 replication. PMID- 1636323 TI - [Clinical pharmacology: current status and perspectives]. AB - In view of the ever increasing complexity of individualized pharmacotherapy, the study of new and potent drugs in man and the misuse and abuse of drugs, WHO-Study Group reports and a recent enquiry in Belgium, France and W. Germany stress that the development of clinical pharmacology is an absolute necessity for patients, physicians, health authorities, the pharmaceutical industry and society at large. It seems this development could be optimally achieved by setting up, within Services of General Medicine or Internal Medicine of University Hospitals and large Public Hospitals, autonomous Units of Clinical Pharmacology with the responsibility to take an active part: a) at the service level: 1) in patient care, either directly in general medical services or drug problem oriented consultations, or indirectly through consultative functions and pharmacotherapeutic conferences; 2) in drug monitoring services, management of cases of overdose, drug information, drug utilization surveys, pharmaco epidemiology, ethical committees, formulary committees, drug regulatory agencies and studies of Phase I, II and III; b) at the teaching level: 1) in courses of clinical pharmacology sui generis, to undergraduates, in close collaboration with the University Department of Pharmacology; 2) at the postgraduate level, as a specialty in se, and as part of the training in medical specialties and at the level of continuing education of general practitioners and specialists; c) at the research level: 1) in clinical pharmacokinetic studies, with special attention to interindividual variability and genetic factors, to drug concentration/effect studies, to drug interactions, and in pharmacodynamic studies, in view of the development of new approaches in the study of drug-receptor interactions; 2) in the design, realization and evaluation of Phase I, II and III studies, clinical trials and multicenter drug studies. PMID- 1636324 TI - Better outcome of patients with traumatic hematomas of the posterior fossa? AB - Within 10 years nearly 500 intracranial hematomas were operated, only 44 concerned the posterior fossa - and only 26 were of traumatic origin. Retrospective observations show that the suspected poor prognosis does not exist as is believed. Factors predicting the outcome are described. PMID- 1636325 TI - [Conservative or surgical treatment for foreign body injuries of the brain]. AB - Presenting our patients with cerebral foreign body injuries since 1954 we find that surgical management is not absolutely indispensable. Criteria for conservative management are presented with illustrative cases. PMID- 1636326 TI - Chronic extradural haematoma--report of 33 cases. AB - During 35 years (1955-1989) 236 extradural haematomas were operated on in the National Institute of Neurosurgery, Budapest. 33 of them were operated on after the 4th day following trauma. These cases were termed as chronic ones. There was no mortality and only two patients had permanent neurological signs. The much more favourable outcome of the chronic extradural haematoma could be explained with the slow development of the haematoma. It is remarkable that the trauma itself was not recognised in several cases. PMID- 1636327 TI - [Psychological counseling of the family of patients with craniocerebral injuries (psychological family counseling of severely ill patients)]. AB - Relatives of 235 brain-injured (BI) patients were observed by trained (psychiatric) staff for psychological coping. This was practiced since 1984 in a BI-rehabilitation ward at a regional psychiatric hospital with 450 beds, serving a catchment area of 330,000. In semi-structured observations patterns of emotional behaviour were registered, which resemble those presented by Kubler Ross for relatives of the dying. Nevertheless important differences were noted: 1. Unrealistic expectations on the relatives' side: caused by insufficient information on differences of physical and cerebral rehabilitation and unfounded belief, transfer from the intensive care section itself signifies the patient's restitution. 2. Unrealistic evaluations: individual consequences of BI may be underrated by relatives, more so if no additional injuries illustrate the patient's severe condition. 2.1. Coma--interpreted as "pseudosleep". Frequently the next of kin are uninformed on the aetiopathology or consequences of coma. Restitution of cerebral functions in various stages of impairment cause confusion, anxiety, resignation even rejection on the side of the relatives. 3. Personality changes: disruptions of personal traits or characteristics as outcome of severe BI are widely known and regarded as formidable consequence. 4. Fear of reintegration; therefore this fear is not infrequent in the next of kin. Additional factors caused by personal history or psychopathology may complicate the issue. Attitudes to rehabilitation are determined by psychological reactions of relatives and may be crucial for the outcome. Recognition of pathological traits and management of psychological attitudes ensures optimal effect of rehabilitation. We noticed several phases in the relatives' psychological changes: acute, initial, protracted and final stage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636328 TI - [Introduction of the Valduna-Reha Scale]. AB - We present a rating scale for the progress in rehabilitation which has been developed and tested in the course of several years. It is of special suitability for the documentation of rehabilitation in cases of dysfunction of the central nervous system due to various syndromes arising from vascular, post-traumatic and post-operative causes. It comprises the essential somatic as well as psychological data and differentiates between specific (e.g. localised) symptoms and their effects on the individual's global functioning, especially within his (her) social sphere. Under this aspect our scale appears to be of optimal use, especially with regard to the requirement: "as simple as possible and as comprehensive as necessary". It modifies the criteria of the WHO regarding the threefold differentiation between impairment, disability and handicap, by the use of two levels of documentation, thereby gaining in validity. PMID- 1636329 TI - [Early rehabilitation of coma patients on the neurosurgical intensive care station. On the philosophy and practice of interdisciplinary cooperation]. AB - The concept of early rehabilitation is an important task of humanity for neurosurgical intensive care patients emerging from coma. In Germany only little experience in this field has been reported, although the concept of early rehabilitation is well known in the other western European countries and the USA. In connection with the author's teaching activities at the pedagogical and psychological departments of the University of Oldenburg, an interdisciplinary concept of communicative "cooperative dialogues" was established for early rehabilitation, beginning in the earliest phases of coma at the neurosurgical intensive care unit. Although the results could not be evaluated statistically yet, the clinical course and outcome of emergence from primary or postoperative coma have improved rapidly by single patients, based on mobilization of neuronal plasticity and self-organized processes. Because of a significant lack of possibilities of early rehabilitation in the northwestern part of Germany, especially for young head injured adults, our efforts will continue. The philosophy and practice of early rehabilitation propose a new interpretation of neurosurgical patients emerging from coma, i.e. a dynamic process of a "second human creation". Early rehabilitation is an important task for the neurosurgically working doctor. Also for the neurosurgical profession the concept of early rehabilitation has to be integrated interdisciplinary to medical teaching at university level as soon as possible. PMID- 1636330 TI - [Fluctuat nec mergitur: professional liability of the surgeon in our current judicial system]. PMID- 1636331 TI - [Medical professional liability insurance: its role, extent, limitations]. PMID- 1636332 TI - [The physics of laser technology]. PMID- 1636333 TI - [Clinical application and risks of surgical lasers]. PMID- 1636334 TI - Reevaluation of quality assurance in the cytology laboratory. PMID- 1636335 TI - "Collagen balls" in peritoneal washings. Prevalence, morphology, origin and significance. AB - Peritoneal washings obtained at laparotomy from women undergoing surgery for neoplasms of the genital tract may contain "collagen balls," consisting of tissue fragments composed of collagen covered with mesothelial cells. Collagen balls were found in 19 (4.5%) of 418 peritoneal washings and were more prevalent in specimens labeled pelvic washings (17 of 294, or 5.8%) than in those labeled peritoneal washings (2 of 124, or 1.6%). In 15 of the 19 cases in which we found collagen balls, at least one ovary was available for microscopic examination. In 14 of the 15 cases minute nodular papillary stromal projections covered with mesothelium were found on the surface of the ovaries. We conclude that collagen balls, a nonspecific entity, most probably originate on the surface of the ovaries. Their significance lies in their being mistaken for mucin-distended cells exfoliated from a neoplasm or from detached fragments of a papillary ovarian neoplasm. PMID- 1636336 TI - Fine needle aspiration of metastatic and hematologic malignancies clinically mimicking pancreatic carcinoma. AB - The fine needle aspiration (FNA) cytology findings in 19 cases of hematopoietic and metastatic neoplasms that radiographically mimicked primary pancreatic carcinoma are reported. These cases represented 11% of 176 malignant diagnoses in a series of 304 pancreatic FNAs. The cytologic diagnoses included 7 non-Hodgkin's lymphomas, 2 Hodgkin's lymphomas, 6 small cell carcinomas (4 lung, 1 gallbladder, 1 skin), 3 squamous cell carcinomas (2 cervix, 1 esophagus) and 1 hepatocellular carcinoma. In six cases the pancreatic lesion was the initial presentation of malignant disease. These included five lymphomas, which probably involved peripancreatic lymph nodes, and a metastatic small cell carcinoma of pulmonary origin. Recognition of unusual morphologic features of pancreatic carcinoma raised the possibility of extrapancreatic malignancies. Electron microscopy and immunocytochemistry performed on FNA specimens were helpful in selected cases. The FNA diagnosis of hematopoietic and metastatic neoplasms that clinically mimic pancreatic carcinoma prompts appropriate clinical studies and treatment and eliminates the need for open pancreatic biopsy and/or resection. PMID- 1636337 TI - Role of esophageal brushing cytology in monitoring patients treated with sclerotherapy for esophageal varices. AB - Recent reports claim that there might be a relationship between sclerotherapy for esophageal varices and cancer of the esophagus. The discovery of a squamous cell cancer of the lower esophagus in a patient treated three years previously with sclerotherapy led us to set up a follow-up protocol. In order to assess this relationship and to monitor the evolution of such lesions, 68 patients treated with sclerotherapy with polidocanol because of esophageal varices were examined endoscopically at six-month intervals, and brushing samples were taken. The ages of the patients ranged between 35 and 81 years, and all had portal hypertension due to cirrhosis; 10 patients with the same disease but without bleeding varices were also examined. The interval between sclerotherapy and the first cytologic follow-up examination averaged 34 months, while the interval to the last follow up examination averaged 40 months. One patient was examined four times (1.4%), 10 three times (14.7%), 39 twice (57.4%) and 18 only once (26.5%). Two cases were interpreted as nuclear hyperplasia associated with inflammation and were found to have regressed at a subsequent examination; all the other cases were reported as negative although sometimes associated with inflammation. None of the controls showed any abnormalities. While the occurrence of esophageal cancer after sclerotherapy might be associated with other risk factors, such as alcohol intake and smoking, esophageal brushing cytology can successfully monitor these patients and detect early stages of neoplasia. PMID- 1636338 TI - Fine needle aspiration cytology of orbital and adnexal masses. AB - Fine needle aspiration (FNA) biopsy was performed on 35 patients with orbital and adnexal masses. Histopathologic study was performed on 15 of the cases. Examples of benign and malignant primary orbital neoplasms, as well as inflammatory lesions diagnosed this way, are described. The diagnostic accuracy of the technique in evaluating orbital masses was 97.1%; there was one false-negative case. The study indicated that this simple technique has considerable diagnostic value in palpable orbital masses. PMID- 1636339 TI - Cytology of allergic conjunctivitis. Presence of airborne, nonhuman elements. AB - Two groups of patients suffering from allergic conjunctivitis (32 atopic, 33 nonatopic) were studied. Their conjunctival secretions were subjected to cytologic examination involving morphologic and semiquantitative evaluation. Account was taken of noncellular and nonhuman elements in the smears; they included mucus, Charcot-Layden crystals, pollen grains, vegetal fragments and fungi. In 12 cases scanning electron microscopy was used in conjunction with x ray microanalysis to identify material of noncellular origin. Similar quantities of inflammatory cells were present in both groups, while epithelial cells, particularly goblet cells, were more numerous in the atopic than in the nonatopic group (21.8% versus 6%). Pollen grains, vegetal fragments and fungi were present in 18%, 55% and 12% of cases, respectively. Exfoliative cytology emerges as a valuable tool for the diagnosis of allergic conjunctivitis, while the presence of noncellular elements is of particular diagnostic significance. PMID- 1636340 TI - A new look at cervical cytology. ThinPrep multicenter trial results. AB - The objective of this study was to compare the sensitivity of a new test method with the smear method for detection of neoplasia of the uterine cervix. The new procedure, the ThinPrep process, is an automated, fluid-based technique for the collection and preparation of exfoliated and aspirated cytologic specimens. A single sample from each patient was split and prepared both with the smear and test methods. The diagnostic results from the two slides were compared in this blind study. Among a total of 2,655 patients, diagnoses concurred in 92% of cases and were within one diagnostic level of each other 98% of the time. The ThinPrep method facilitated the detection of more low-grade lesions (P less than .001, McNemar's test). In addition, the test method decreased the number of ambiguous interpretations. The ThinPrep method appears to improve the cervical cytologic smear quality by the harvest of a random and reproducible sample, with a reduction in artifacts. The new method improves the sensitivity of the cervical cytologic screening test. PMID- 1636341 TI - Filarial infection of the breast. Report of a case with diagnosis by fine needle aspiration cytology. AB - The breast is not a frequent site of filarial infection. We report a case of fine needle aspiration cytologic diagnosis of filariasis of the breast, not previously reported. PMID- 1636342 TI - Secretory carcinoma of the breast. Report of a case with diagnosis by fine needle aspiration. AB - We report a case of secretory carcinoma of the breast in a 63-year-old woman studied by fine needle aspiration (FNA). The cytologic features included solid nests, cohesive sheets and isolated tumor cells with intracytoplasmic vacuolization and signet-ring-like forms. Although secretory carcinoma is an unusual breast tumor, especially in adults, the cellular morphology was distinctive on FNA. This could permit the preoperative diagnosis of secretory carcinoma and the planning of optimal surgical therapy prior to an intervention. PMID- 1636343 TI - Neurilemoma of the breast in a man. A case report. AB - A case of neurilemoma of the left breast in an 83-year-old man is presented, including the fine needle aspiration and biopsy diagnosis. A review of the literature did not reveal the existence of such a tumor in a man's breast. The aspirate yielded a cellular smear composed of clusters of spindle-shaped cells showing minimal atypia and Verocay bodies. The final diagnosis was established on the excised mass through histopathologic study. PMID- 1636344 TI - Needle aspiration biopsy of vulvar endometriosis. A case report. AB - Vulvar involvement by endometriosis is extremely rare. A patient presented with a vulvar tumor and was diagnosed on needle aspiration biopsy and subsequently on histopathology as having endometriosis of the vulva. The treatment offered was conservative, local excision of the tumor. The patient was well and free of complaints when last seen in the Outpatient Department, at six months of follow up. Needle aspiration biopsy as a diagnostic tool in vulvar tumors and the histogenesis of the endometriosis are discussed. PMID- 1636345 TI - Fine needle aspiration cytology diagnosis of tuberculous thyroiditis. A report of eight cases. AB - Among 1,283 cases of thyroid lesions subjected to fine needle aspiration cytology (FNAC) over a period of two years, 8 cases (0.6%) were found to be having cytologic features consistent with tuberculous thyroiditis. The ages of the patients ranged from 14 to 65 years, with a median of 30. The male:female ratio was 4:4. Six cases clinically presented with solitary nodules of the thyroid and two cases as abscesses in the thyroid region. Three patients had concomitant cervical lymphadenopathy, and only two patients were known cases of tuberculosis on treatment. Ultrasonography, done in seven cases, confirmed solitary nodules in four; in one case the differentiation between an extrathyroid nodule and cystic isthmic nodule was difficult, and in the remaining two cases the lesions were found to be extrathyroid. Fine needle aspirates from thyroid swellings showed epithelioid granuloma with necrosis in five cases and necrosis without epithelioid granuloma in three cases. The number of cases positive for acid-fast bacilli in these two groups were two and three, respectively. Lymph node aspiration, done in three cases, revealed necrotic material in two; both were positive for acid-fast bacilli, and the third case showed epithelioid granuloma without necrosis. PMID- 1636346 TI - Cytologic features of poorly differentiated "insular" carcinoma of the thyroid. A case report. AB - A case of poorly differentiated "insular" carcinoma of the thyroid is presented. Fine needle aspiration cytology suggested the differential diagnosis of poorly differentiated carcinoma versus anaplastic carcinoma. Histologic examination of the resected specimen confirmed the diagnosis of insular carcinoma. The cytologic features of this uncommon primary thyroid malignancy are described and discussed with reference to the literature. PMID- 1636347 TI - Disseminated histoplasmosis diagnosed by percutaneous needle biopsy of a retroperitoneal lymph node. A case report. AB - A case of disseminated histoplasmosis diagnosed by percutaneous needle biopsy cytology is reported. The patient presented with fever and pancytopenia. Computed tomography (CT) revealed retroperitoneal lymphadenopathy. Cytology smears prepared from a CT-guided screw needle biopsy of one of the lymph nodes showed numerous histiocytes with intracytoplasmic yeast forms consistent with Histoplasma capsulatum. Fungal cultures prepared from additional needle biopsy material confirmed the diagnosis. This case illustrates the utility of needle biopsy in the evaluation of radiographically detected retroperitoneal lymphadenopathy and in the rapid diagnosis of infectious disease in certain clinical settings. PMID- 1636348 TI - Fine needle aspiration cytology of silicone lymphadenopathy in a patient with an artificial joint. A case report. AB - Three years after replacement of the left first metatarsophalangeal joint with a silicone prosthesis, a patient noted enlargement of a left femoral lymph node. Fine needle aspiration of the node revealed a foreign body giant cell reaction to particulates morphologically compatible with silicone elastomer. This finding suggests the potential utility of fine needle aspiration in the evaluation of patients' responses to a variety of foreign materials used in prosthetic devices and as pharmaceuticals. PMID- 1636349 TI - Primary cecal lymphoma. Report of a case with preoperative diagnosis by fine needle aspiration and immunocytochemistry. AB - Fine needle aspiration of a cecal mass was performed on a patient with a cecal tumor and iron-deficiency anemia. Cytologic studies of the air-dried smears showed large cell lymphoma. The diagnosis of large cell lymphoma of the B-cell type was affirmed by immunocytochemical studies and at laparotomy and resection of the tumor. Even under unusual circumstances, the diagnosis of such a rare abdominal lesion as primary cecal lymphoma can be made with certainty by cytologic and immunologic studies of fine needle aspirates. PMID- 1636350 TI - Ameloblastic fibroma. Report of a case with fine needle aspiration cytologic findings. AB - A case of ameloblastic fibroma of the jaw in an 18-year-old patient is presented. Fine needle aspiration cytologic smears showed two different types of cellular elements: a glandlike epithelial component, arranged in bidimensional, well outlined clusters of basaloid cells with palisading of the columnar cells at the borders of those clusters, and a mesenchymal component that consisted of loosely arranged fusiform cells. These cytologic features appear to be sufficiently characteristic to suggest a diagnosis of ameloblastic fibroma by fine needle aspiration. PMID- 1636351 TI - Endoscopic brushing cytology of primary gastric choriocarcinoma. A case report. AB - A rare primary choriocarcinoma of the stomach developed in a 71-year-old woman admitted with epigastric pain and weight loss. Brushing smears revealed highly atypical malignant cells with bizarre nuclei and prominent nucleoli. Multiple histologic sections revealed pure choriocarcinoma. Human chorionic gonadotropin and keratin were demonstrated in malignant cells by immunohistochemistry. PMID- 1636352 TI - Osteitis fibrosa cystica (brown tumor) in a patient with renal transplantation. Report of a case with aspiration cytodiagnosis. AB - The cytologic findings from fine needle aspiration of a left shoulder mass are described for a woman who had undergone renal transplantation and on whom an orthopedic consultation suggested the clinical possibility of a soft tissue sarcoma. The aspirate samples from multiple sites in the mass showed several multinucleate, osteoclast-type giant cells, spindly or fibrillary cells with ovoid nuclei and a significant amount of granular calcium. The needle aspiration cytodiagnosis was of critical importance since it saved the patient from invasive surgical intervention. This case emphasizes the role of needle aspiration cytology in providing a rapid cytodiagnosis of osteitis fibrosa cystica with a minimally invasive method. PMID- 1636353 TI - Elastofibroma dorsi. Cytologic, histologic, immunohistochemical and ultrastructural studies. AB - Cytologic, light and electron microscopic, and immunohistochemical studies were conducted on a case of elastofibroma. Aspiration cytology showed a characteristic "braidlike" or "fern leaf-like" structure. Immunohistochemically the accumulate was shown to be elastin. Transmission electron microscopy indicated electron dense, granular aggregates surrounded by microfilaments and collagen, while scanning electron microscopy revealed balls with a ball-of-yarn-like structure consisting of small fibrils, probably of elastin. These structures are unique to this disease and useful for diagnosis. PMID- 1636355 TI - 40th annual scientific meeting of the American Society of Cytology. Quebec City, Canada, September 29-October 4, 1992. Abstracts. PMID- 1636354 TI - Fine needle aspiration cytology in malignant Sertoli cell tumor of the testis. A case report. AB - A rare case of malignant Sertoli cell tumor of the testis occurred in which the diagnosis was initially suggested on fine needle aspiration cytology. Smears of the testicular, inguinal and cervical lymph node aspirates showed cells resembling normal Sertoli cells arranged in nests and tubules. Histopathology of the orchidectomy specimen confirmed the diagnosis. The literature is briefly reviewed. PMID- 1636356 TI - Polypoid carcinoma of the esophagus on brush cytology. PMID- 1636357 TI - Clinical evaluation of the ThinPrep method for the preparation of nongynecologic material. PMID- 1636358 TI - Avoiding unreadably thick Cytospin preparations. PMID- 1636359 TI - Diagnosis of occult ovarian carcinoma in endometrial smears. PMID- 1636360 TI - Noninvasive measuring methods for the investigation of irritant patch test reactions. A study of patients with hand eczema, atopic dermatitis and controls. AB - The aim of the study was to assess the susceptibility of clinically normal skin to a standard irritant trauma under varying physiological and patophysiological conditions. Evaluation of skin responses to patch tests with sodium lauryl sulphate (SLS) was used for assessment of skin susceptibility. The following noninvasive measuring methods were used for evaluation of the skin before and after exposure to irritants: measurement of transepidermal water loss by an evaporimeter, measurement of electrical conductance by a hydrometer, measurement of skin blood flow by laser Doppler flowmetry, measurement of skin colour by a colorimeter and measurement of skin thickness by ultrasound A-scan. The studies were carried out on healthy volunteers and patients with eczema. In the first studies the standard irritant patch test for assessment of skin susceptibility was characterized and validated. SLS was chosen among other irritants because of its ability to penetrate and impair the skin barrier. The implications of use of different qualities of SLS was investigated. The applied noninvasive measuring methods were evaluated, and for quantification of SLS-induced skin damage measurement of TEWL was found to be the most sensitive method. Application of the standard test on clinically normal skin under varying physiological and patophysiological conditions lead to the following main results: Seasonal variation in skin susceptibility to SLS was found, with increased susceptibility in winter, when the hydration state of the stratum corneum was also found to be decreased. A variation in skin reactivity to SLS during the menstrual cycle was demonstrated, with an increased skin response at day 1 as compared to days 9-11 in the menstrual cycle. The presence of active eczema distant from the test site increased skin susceptibility to SLS, indicating a generalized hyperreactivity of the skin. Taking these sources of variation into account healthy volunteers and patients with hand eczema and atopic dermatits were studied and compared. In healthy volunteers increased baseline TEWL and increased light reflection from the skin, interpreted as "fair" skin, was found to be associated with increased susceptibility to SLS. Hand eczema patients were found to have fairer and thinner skin than matched controls. Increased susceptibility to SLS was found only in patients with acute eczema. Patients with atopic dermatitis had increased baseline TEWL as well as increased skin susceptibility as compared to controls. Skin susceptibility is thus influenced by individual- as well as environment related factors. Knowledge of determinants of skin susceptibility may be useful for the identification of high-risk subjects for development of irritant contact dermatitis, and may help to prevent the formation of the disease. PMID- 1636361 TI - Mechanisms of skin adherence, penetration and tissue necrosis production by Haemophilus ducreyi, the causative agent of chancroid. AB - Haemophilus ducreyi (H. ducreyi) strains, representing both reference strains and low-passage isolates, were investigated in terms of surface structures and enzymatic equipment. The interaction of these factors with host tissue was analysed using new in vitro- and in vivo-models. By electron microscopy studies there was no evidence of an extracellular capsule or surface appendages such as pili or flagella. Interaction of all isolates tested with the lectin Phaseolus vulgaris suggests N-acetyl-D-glucosamine units as common structural features of H. ducreyi cell envelope polysaccharide. In attachment to epithelial cells more than one hemagglutinin might be implicated as different haemagglutination patterns could be observed whereby the activity was not heat-labile, but was abolished by formaldehyde. Hydrophobic interactions might be of importance as well as strains showed a wide range of reactions from hydrophobic to hydrophilic, low hydrophobicity being more marked with the older strains. No elaboration of degradative enzymes based on the measurement of enzymatic activity using insoluble dye-protein complexes could be detected in case of H. ducreyi, using Azocoll and Remazol Brilliantblue hide powder for detection of proteolytic activity and elastinorcein for detection of elastase activity. In vitro studies using human keratinocytes and Vero cells did not show any morphological changes when incubated with H. ducreyi culture filtrates. In vivo studies with a new mouse model for H. ducreyi infection could confirm the results of the in vitro studies. Mere contact to undamaged skin both of whole cell organisms, live or heat-killed, and of culture filtrates did not lead to any reaction or even damage of mouse skin. However, when the outer epidermal layer was overcome by intradermal injection of shaved mice ulcers developed. Tissue necrosis production was not bound to live organisms as dead ones showed the same effect. There is great evidence that this tissue necrosis is associated with H. ducreyi lipopolysaccharide (LPS) because intradermal injection of purified H. ducreyi LPS lead to the same reaction pattern. For the first time a cell mediated immune response could be demonstrated in case of H. ducreyi infection as different antigen preparations of H. ducreyi isolates induced proliferation of lymphocytes isolated from healthy unexposed individuals and from a chancroid-sensitized male. In the latter case measured cell responses were much stronger. The dose-dependent phenomenon was associated with interleukin-2 production. In summary, H. ducreyi isolates do not exhibit cytotoxic effects on the epithelial cells of the skin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1636363 TI - Career advancement for nurses--what is it? A joint venture of three Calgary hospitals. PMID- 1636362 TI - The economics and politics of health care system ailments. PMID- 1636364 TI - Spirituality: implications for nursing care. PMID- 1636365 TI - Community action research teams in population focused nursing a post diploma learning experience. PMID- 1636366 TI - The Florence Nightingale lamp. PMID- 1636367 TI - Screen test update, program activity, and cancer detection rates. PMID- 1636368 TI - The promotion of the image of nurses. PMID- 1636369 TI - Politically--taking action. PMID- 1636370 TI - [Lacunar syndromes due to intracerebral hemorrhage]. AB - Nine cases (seven men and two women, mean age 64.5 years) of classical lacunar syndromes due to intracerebral hemorrhage are reported. Three patients presented with pure motor hemiparesis (two putaminal hematomas with proportional weakness and one cortical hemorrhage with brachio-crural hemiparesis). Four patients presented with sensorimotor stroke due to thalamo-capsular hemorrhage. The last two patients had thalamic hemorrhage causing ataxic hemiparesis or dysarthria clumsy hand syndrome. Four subjects had arterial hypertension, one was diabetic, and two were treated with anti-vitamin K. Abrupt onset was noted in all instances. Only one patient experienced moderate inaugural headaches. Good recovery occurred in all cases. Lacunar syndromes are a very uncommon presentation of intracerebral bleeding. Hemorrhages are yet the second etiology of such syndromes. Distinguishing hemorrhage from infarction is not clinically possible and needs early unenhanced CT scan. PMID- 1636371 TI - Muscle cramp as a feature of neuromuscular disease. Five neuromuscular disorders, accompanied by frequent muscle cramps. AB - Five case reports of neuromuscular disorders, presenting with frequent muscle cramps are discussed. Clinical diagnosis and pathophysiologic concepts are highlighted. PMID- 1636372 TI - Movement disorders due to cerebral Toxoplasma gondii infection in patients with the acquired immunodeficiency syndrome (AIDS). AB - Hemichorea and parkinsonism are unusual manifestations of cerebral toxoplasmosis in patients with AIDS. We here describe two such cases and we reviewed extensively the literature (through computer searches using MEDLINE) for other reported instances. In our patients, unlike the other neurological symptoms, the response of the movement disorders to anti-toxoplasmosis therapy was delayed and only partial. We demonstrate that tetrabenazine is a valuable additional symptomatic treatment for choreic movements in one of our patients. We emphasize that, among patients suffering from AIDS, particularly in countries with high prevalence of toxoplasmosis, the occurrence of movement disorders should first suggest the diagnosis of cerebral toxoplasmosis. PMID- 1636373 TI - Inefficiency of metal chelators to promote recovery of methylmercury inhibited CNS succinic dehydrogenase. AB - This paper deals with the level of succinic dehydrogenase (SDH) in various locations of the central nervous system (CNS) of rat, treated with methylmercury chloride (MMC) and later with antagonists. None of the CNS areas reveals any effect after 2 days of MMC application, but further treatment causes a linear inhibition of the enzyme with increasing duration of MMC exposure. Maximal inhibition in all regions is exhibited after 15 days of treatment. In absolute terms, the maximal inhibition is observed in the olfactory bulbs and the minimal effect is seen in the spinal cord after 15 days with low and high doses of MMC respectively. PMID- 1636374 TI - Human glial fibrillary acidic protein (GFAP): molecular cloning of the complete cDNA sequence and chromosomal localization (chromosome 17) of the GFAP gene. AB - We isolated three glial fibrillary acidic protein (GFAP) cDNA clones from a glioma cell line, U-251 MG. One clone isolated from a U-251 MG cDNA library was long, but lacked both ends. Using poly(A)+ RNA and primers synthesized according to the sequence of this clone, we used the polymerase chain reaction-assisted rapid amplification of cDNA ends (PCR-RACE) method, which is a strategy to isolate cDNA ends, and obtained cDNA clones for the 5' and 3' ends. From the sequences of these overlapping clones, the complete nucleotide sequence of human GFAP cDNA was established. The start (ATG) and the stop (TGA) signals were seen at nucleotide positions 15 and 1311, respectively, and divided the entire sequence of 3027 bp into 14 bp of 5' non-coding, 1296 bp of coding and 1717 bp of 3' non-coding regions. Using cDNA probes made from both the coding and the 3' non coding regions, Northern blot hybridization was performed with two different stringencies on RNAs from human and rodent brains and human GFAP-positive and negative cells. It was shown that the 3' non-coding region probe was more specific for human GFAP than the coding region probe which was specific only under higher stringency conditions. This was also suggested by homology analysis of the sequence with those of various intermediate filament proteins. Based on these findings, we performed spot blot hybridization of sorted human chromosomes and Southern blot hybridization of PCR-amplified DNAs of a panel of hamster-human somatic cell hybrids and localized the human GFAP gene to chromosome 17. PMID- 1636375 TI - Basophilic inclusions in sporadic juvenile amyotrophic lateral sclerosis: an immunocytochemical and ultrastructural study. AB - This report concerns immunocytochemical and ultrastructural studies on the basophilic inclusions in two cases of sporadic juvenile amyotrophic lateral sclerosis (ALS). The inclusion had a globular, irregular-shaped, or sometimes fragmented appearance. Ultra-structurally, the inclusions consisted mainly of thick filamentous structures associated with granules. Focal neurofilamentous accumulations were occasionally observed among the granulofilamentous structures. The basophilic inclusions occasionally showed granular reaction product deposits with an antibody to ubiquitin. The inclusions did not react with antibodies to phosphorylated neurofilament and to tau protein. PMID- 1636376 TI - Comparison of behavior in muscle fiber regeneration after bupivacaine hydrochloride- and acid anhydride-induced myonecrosis. AB - We compared the morphologic characteristics of muscle fiber necrosis and subsequent regeneration after injury induced by intramuscular injections of bupivacaine hydrochloride (BPVC) and a variety of solutions at acid and alkaline pH (acetic anhydride, citric acid buffer, and sodium carbonate buffer). After BPVC injection the necrotic muscle fibers were rapidly invaded by phagocytic cells, followed by active regeneration and very little fibrous scar formation. The regenerating muscle fibers increased rapidly in size and attained complete fiber type differentiation and regained their initial fiber diameter within 1 month. Both alkaline and acid solutions induced muscle fiber necrosis followed by regeneration. Fiber necrosis induced by alkaline buffers and acetic anhydride solutions above pH 5.0 produced changes quite similar to that induced by BPVC. However, injection with 0.1 M acetic anhydride at pH below 4.0 resulted in coagulative necrosis of the injured muscle with very little phagocytic infiltration with poor regenerative activity and dense fibrous tissue scarring. Thus, pH 4.0 appears to be the critical pH determining the type of muscle injury and subsequent poor phagocytic and regenerative activities. This model of acidic acetic anhydride injury may lead to the identification of factors which interfere with regeneration and cause fibrous tissue scarring in human muscular dystrophy. PMID- 1636377 TI - Immunophenotypic analysis of infiltrating leukocytes and microglia in an experimental rat glioma. AB - The appearance and cellular distribution of major histocompatibility complex (MHC), as well as lymphocytic and macrophage antigens has been studied in a fully developed experimental rat forebrain glioma. Activated microglial cells and microglia-derived macrophages expressing CR3 complement receptor molecules and MHC class II (Ia) antigen were found throughout the tumor, and with increased density along the tumor's periphery. MHC class I antigen expression was entirely absent from tumor cells, and found only occasionally on microglia. The expression of leukocyte common antigen, and CD4 and CD8 antigens was conspicuous throughout the tumor, and associated with lymphocytes, perivascular cells, and microglia. Cells expressing the ED2 macrophage epitope were almost exclusively of the perivascular type and revealed a distribution dissimilar to that of cells positive for Ia antigen. The ED2 epitope was found sporadically on ramified microglial cells. The results show that despite heavy infiltration with blood mononuclear and CNS microglial cells, the tumor showed no evidence of destruction caused by inflammatory cells. Possible mechanisms of tumor immunosuppressive activity preventing the full immunological activation of microglia and blood mononuclear cells are discussed. PMID- 1636378 TI - Colloid cysts of the third ventricle: ultrastructural features are compatible with endodermal derivation. AB - The histogenesis of colloid cyst of the third ventricle remains unsettled. Ultrastructural and immunohistochemical analyses have suggested the following possible origins: (a) neuroepithelium, including paraphysis, ependyma, choroid plexus and tela chorioidea; and (b) endoderm, including respiratory and enteric epithelium. This report describes the ultrastructural features of the lining epithelium in four cases of colloid cyst. Six distinct cell types were recognized: (1) ciliated cells with occasional abnormal cilia; (2) non-ciliated cells with microvilli coated with granulofibrillary material; (3) goblet cells showing discharge of secretory granules; (4) basal cells with prominent tonofilaments and desmosomes; (5) basal-located cells with elongated electron lucent cytoplasm and scattered membrane-bound dense-core granules (150-350 nm); and (6) small undifferentiated cells with scanty organelles. Junctional complexes were present in the former four cell types but absent in the latter two. The types of epithelial cells and their topographic distribution within the epithelium are both very similar to those of normal respiratory epithelium and to the lining epithelium of intraspinal bronchogenic cyst. The observations made in the present study are compatible with the hypothesis that colloid cysts of the third ventricle originate from the endoderm, most likely the respiratory epithelium. PMID- 1636379 TI - Metabolically dependent blood-brain barrier breakdown in chronic relapsing experimental allergic encephalomyelitis. AB - We have studied chronic relapsing experimental allergic encephalomyelitis (CREAE), a model of immune-mediated demyelination, using gadolinium (Gd)-enhanced magnetic resonance imaging in vivo and the blood-brain barrier (BBB) markers, lanthanum nitrate and Gd nitrate, histologically. In regions of the spinal cord showing Gd enhancement, there was evidence for vesicular transport as a mechanism of BBB breakdown in CREAE, shown by an increased number of endothelial vesicles containing lanthanide (lanthanum or Gd, whichever had been perfused) and deposition of tracer in the perivascular space; tight interendothelial junctions remained intact. Prior perfusion with 2,4-dinitrophenol, a metabolic inhibitor, suppressed the appearance of endothelial vesicles containing lanthanide and tracer in the perivascular space. We conclude that an important contribution to BBB breakdown in CREAE is mediated by a metabolic change in the endothelial cells associated with increased vesicular transport. PMID- 1636380 TI - Abnormal local-circuit neurons in epilepsia partialis continua associated with focal cortical dysplasia. AB - A limited cortical resection including the rolandic fissure and the pre- and postcentral cortical regions was carried out in a patient suffering from epilepsia partialis continua resistant to antiepileptic drugs. The histological examination revealed several foci of very large neurons distributed with no laminar organization in the depth of the rolandic fissure and in the crown of the primary motor and primary somatosensory areas; these lesions were consistent with focal cortical dysplasia. In addition, decreased numbers of neurons, astrocytosis and proliferation of capillaries, compatible with chronic tissue necrosis, were found in the inferior regions of the banks of the rolandic fissure. Subpopulations of local-circuit neurons were examined with parvalbumin, calbindin D-28k and somatostatin immunocytochemistry. Focal areas of cortical dysplasia contained abnormal immunoreactive neurons. Huge parvalbumin-immunoreactive cells were distributed at random and resembled axo-axonic (chandelier) and basket neurons. Abnormal calbindin D-28k-immunoreactive cells were reminiscent of double bouquet neurons and multipolar cells. Very large somatostatin-immunoreactive cells were seldom observed in the dysplastic foci. On the other hand, areas of tissue necrosis displayed massive reduction of immunoreactive cells and fibers. Abnormalities in the morphology and distribution of local-circuit (inhibitory) neurons observed here for the first time in focal cortical dysplasia may have a pivotal role in the appearance and prolongation of electrical discharges and continuous motor signs in human focal epilepsy. PMID- 1636381 TI - Tubuloreticular structures in microglial cells, pericytes and endothelial cells in Alzheimer's disease. AB - In two of six brain biopsies of patients with Alzheimer's disease (AD), tubuloreticular structures (TRS) were observed in the distended endoplasmic reticulum of microglial cells, endothelial cells of vessels, and pericytes. In the microglial cells that produce amyloid fibrils, TRS were found in the cytoplasmic channels, which were filled with newly formed amyloid fibrils. Co localization of TRS and newly formed amyloid fibrils in the same cellular compartment strengthens the hypothesis that amyloid fibrils are formed in the endoplasmic reticulum of microglial cells. Formation of TRS in microglial cells, pericytes, and endothelial cells of vessels probably reflects local or systemic alpha-interferon production. In some cells, this pathological process coexists with the second type of pathological changes: formation of amyloid fibrils. PMID- 1636382 TI - Cystic brain stem necrosis in a premature infant after prolonged bradycardia. AB - A case is described of symmetrical cavitating brain stem necrosis produced by cardiac arrest in a premature infant. Two months after birth this 25-week gestational age infant suffered a prolonged episode of bradycardia. She was resuscitated and then died 3 weeks later. The autopsy revealed striking bilateral cavitation of the brain stem tegmentum extending in a columnar fashion from the upper portion of the spinal cord to the hypothalamus. The findings in this case are identical to the brain stem injury experimentally produced by complete cardiac arrest in the rhesus monkey. PMID- 1636383 TI - An unusual demyelinating neuropathy in a patient with Waardenburg's syndrome. AB - We present clinical and laboratory data from a patient with Waardenburg's syndrome type II comprising iris heterochromia and deafness, complicated by Hirschsprung's disease--a known association--and an unusual demyelinating peripheral neuropathy--a unique association. The neuropathy is characterised by excessive focal folding of myelin sheaths. It is our view that, although both disorders could represent the consequences of neural crest embryopathy, it is more likely that they are associated by chance. PMID- 1636384 TI - Angelman's syndrome: a neuropathological study. AB - We report the neuropathological findings of a 3-year-old boy with Angelman's syndrome. The main abnormalities were macroscopic consisting of small temporal and frontal lobes which also showed disorganised and irregular gyri. The occipital lobes appeared flattened but were otherwise normal as were the parietal lobes. The brain stem and cerebellum appeared normal externally. Microscopically there was irregular distribution of neurons in layer 3 and in the cerebral white matter a few subcortical ectopic neurons were present in the temporal and frontal lobes. A single "Purkinje" cell heterotopia was seen but otherwise the cerebellum appeared normal. PMID- 1636385 TI - Conjunctival malignant melanoma in Sweden 1969-91. AB - Clinical information, follow-up and histopathological parameters of the primary lesions were assessed for all (45) individuals with conjunctival malignant melanomas in Sweden presenting during a 22.5 year period (1969 to mid 1991). The annual incidence of conjunctival malignant melanoma in Sweden was 0.0240 per 100,000. On average, two new cases were diagnosed each year (population 8.6 million in 1991). Sixty-two per cent of the lesions recurred, but re-growth in itself was not correlated to reduced survival. The actuarial 10-year survival proportion using life-table analysis was 70%. A significantly reduced survival due to tumour-related death was noted in patients with tumours with high mitotic indices, many epithelioid cells and in lesions exceeding 10 mm in diameter. Other factors that may influence survival are presented in the context of previous reports. The present policy in Sweden for treating patients with malignant melanoma of the conjunctiva is outlined and discussed. PMID- 1636386 TI - In vitro ingrowth of choroidal cells on Bruch's membrane. AB - Full thickness eyewall explants were made from human eyes, the retina and retinal pigment epithelium were removed, and the explants were maintained in vitro in Ham's F-10 medium with 20% foetal bovine serum. Cultured explants were examined by scanning and transmission electronmicroscopy after varying lengths of time. When in vitro, choroidal cells migrated across the cut edge of the explant onto the denuded Bruch's membrane where they subsequently showed production of extracellular matrix. In the human eye, ingrowth of choroidal cells on Bruch's membrane is found in macular degenerations, inflammatory chorioretinal disorders and subsequent to trauma. The in vitro model system presented in our study could facilitate evaluation of the dynamics underlying such ingrowth and also of factors affecting the course of this process. PMID- 1636387 TI - The influence of argon laser panretinal photocoagulation on the rabbit ERG c wave. AB - We observed the influence of panretinal photocoagulation on the ERG c-wave in rabbit eyes. DC-registered ERGs were recorded from rabbit eyes before and after photocoagulation, and compared with those of the fellow eyes. The rabbits were subdivided into 3 groups according to application numbers: 500, 1000, and 1500 spots. The ERG c-waves were found to have totally disappeared in all rabbits 3 days after panretinal photocoagulation, then reappeared with various intervals. In the 500 spot group, the c-wave reappeared after one week, and almost reached control levels in one and a half months. In the 1000 spot group, a 10 day delay was noted, and 90% of control levels were regained after 6 months. In the 1500 spot group, the c-wave didn't reappear until 2 weeks later, and regained 70% (of the control level) after 6 months. The recovery rates were related to the number of laser applications. These results indicate that the ultimate degree of recovery in c-wave amplitude and the time required for the reestablishment of retinal pigment epithelium function both depend on the size of the coagulated area. PMID- 1636388 TI - The prevalence and type of glaucoma in geriatric patients. AB - A group of 100 institutionalized geriatric patients aged 69-94 years (mean 81.2 years) was studied at Koskela Helsinki Municipal Hospital. The selection of the patients was randomized by taking 100 patients having a birth-date divisible by five. Glaucoma occurred in 15% of the patients (14 women and one man). Six patients had bilateral primary open-angle glaucoma. One patient had capsular glaucoma in one eye and secondary glaucoma in the other eye. Eight patients had glaucoma only in one eye; three narrow-angle glaucoma, three primary open-angle glaucoma and two secondary glaucoma. Exfoliation occurred in 21 patients (26%, 21/80). Ten patients had bilateral exfoliation and 11 exfoliation only in one eye. IOP was measured in 75 patients, 150 eyes, with applanation tonometry, averaging 12.5 mmHg (SD 5.0), and in 22 patients, 44 eyes, with Schiotz tonometry, averaging 16.3 mmHg (SD 5.6). Visual acuity for long distance and also the reading acuity were greater than 0.3 in 66% (54/82). PMID- 1636389 TI - Long-term post trabeculectomy intraocular pressures. AB - Eighty-one eyes which had had trabeculectomy with a mean follow-up period of 9.2 years (range 7 to 10 years) were studied retrospectively for their subsequent pattern of intraocular pressure. Of 43 chronic open-angle glaucoma eyes, 29 (67%) had their pressures maintained below 21 mmHg by trabeculectomy alone over a 7-10 year period. On the other hand, 25 of 38 (65%) eyes with other types of glaucoma required an average of 1.5 different antiglaucoma medications post-op for the control of their intraocular pressures. Fifteen of 69 (22%) phakic eyes required cataract extraction at a mean of 5.1 years post-op. Two of 43 (5%) chronic open angle glaucoma eyes suffered blinding complications attributable to the procedure. Seventeen percent: of eyes gained visual field at a mean of 7% of the pre-op field per year following trabeculectomy. Fifty percent lost field at a mean rate of 2.3% per year. PMID- 1636390 TI - Myopia among medical students in Norway. AB - In this study the prevalence of myopia and age at onset among medical students were determined. Of the 140 senior medical students at The Faculty of Medicine, University of Trondheim, Norway, 133 (75 females, 58 males) were examined. Visual acuity was tested and the refractive error was measured using automated refraction and clinical refractive technique. The prevalence of myopia was found to be 50.3% in the right eye (n = 67) without significant difference between female and male students. The refractive state was unrelated to body height. Among the myopic students, the mean equivalent sphere was -2.34 +/- 2.01 D in the right eye (range -9.25 D to -0.25 D). A clear relationship was detected between the current amount of myopia and the age at which corrective lenses were first prescribed. However, as much as 43.3% of the myopic students wearing corrective lenses first received these at the age of about 20 years, indicating a relatively high prevalence rate of adult-onset myopia. PMID- 1636391 TI - Effect of number of test points and size of test field in automated perimetry. AB - Sensitivity variation in normal subjects was studied, by changing the number of test locations and the size of test fields on automated perimetry. Using the Sargon program, four different programs that differed in the number of test points or in the size of test field were made. Mean sensitivity and short-term fluctuation were calculated from the same test points of each program. The program with the fewest points and the smallest size produced the greatest sensitivity and the least fluctuation. Our results showed that the number of test points and the size of test field affected the sensitivity and its reproducibility in automated perimetry. PMID- 1636392 TI - Repeatability, reproducibility and intersession variability of the Allergan Humphrey ultrasonic biometer. AB - We evaluated repeatability and reproducibility of the Allergan Humphrey model 820 ultrasonic biometer. Sixty eyes (30 subjects) free from ophthalmological abnormality were examined on two separate occasions by two experimenters, one experienced and one inexperienced. The 95% confidence limits for repeatability lie between +0.12/-0.13 mm and reproducibility between +0.15/-0.14 mm for AC depth, between +0.11/-0.13 mm and +0.12/-0.16 mm for lens thickness, between +0.17/-0.19 mm and +0.19/-0.18 mm for right axial length and between +0.26/-0.40 mm and +0.22/-0.25 mm for left axial length. The 40% gain used to measure left axial lengths produced poor retinal echospikes, which may account for reduced accuracy compared to the right eyes using 60% gain. Ten subjects (20 eyes) returned for 3 further visits and the variability over 5 sessions was examined using a two-factor ANOVA with repeated measures on one factor. There were no significant experimenter or session effects and no interaction effect. This biometer gives clinically repeatable and reproducible results and is convenient to use. PMID- 1636393 TI - Conjunctival eosinophilia in atopic and non-atopic external eye symptoms. AB - We studied the occurrence in an ophthalmological office practice of conjunctival eosinophilia in 333 normal subjects (mean age 26 years) and in 152 atopic and 484 non-atopic patients (mean age 40 years) with various external eye symptoms. Eosinophils were present in 131/636 patients (21%) and in 22/333 asymptomatic normal subjects (7%). In those patients with conjunctival eosinophilia, a history of some kind of atopic condition was obtained only in 53/131 (40%). When the patients were characterized according to the presence of both eosinophilia and atopy, eosinophilia without signs of atopy was observed in 7-15% in different diagnostic groups. Patients with conjunctivitis or blepharoconjunctivitis had a fourfold risk for eosinophilia compared to normal subjects (odds ratios 4.52 and 4.09, confidence intervals 2.02, 10.12 and 2.40, 6.99), when atopy, sex, age, time of the examination and presence of bacteria were included as potential confounders in the regression model. We conclude that a considerable portion of patients with external eye symptoms, and especially with various forms of conjunctivitis, show eosinophilic inflammation without any evidence of atopic background. They can be labelled as having 'intrinsic' eosinophilic conjunctivitis analogously to the classification used in patients with intrinsic rhinitis and asthma. The etiology of this common nonatopic syndrome remains to be established. PMID- 1636394 TI - The effect of sodium cromoglycate eyedrops compared to the effect of terfenadine on acute symptoms of seasonal allergic conjunctivitis. AB - A multicentre, group comparative open study was carried out on 68 patients to compare the effects of 2% sodium cromoglycate eyedrops and an oral antihistamine, terfenadine, on acute symptoms of seasonal allergic conjunctivitis. The study was continued for one week after the onset of acute symptoms. Both medications were equally efficient in reducing symptoms during the first hour of observation. During the one-week follow-up both medications reduced symptoms to a low level, and both medications were equally effective for allergic symptoms, except that terfenadine was more effective in reducing the watering of eyes. PMID- 1636395 TI - Tear film profile in Graves' ophthalmopathy. AB - Tear film profile was studied in 30 patients with Graves' ophthalmopathy. Tear film pH, fluorescein staining, marginal tear strip and Schimer test values in patients with Graves' ophthalmopathy were comparable with controls, indicating normal tear secretion. Tear film break-up-time (BUT) in late Graves' ophthalmopathy was significantly low suggesting unstable tear film. Rose bengal as well as lissamine green staining intensity scores were significantly high, indicating presence of drying epithelial cells in early as well as late Graves' ophthalmopathy patients. PMID- 1636396 TI - Changes with age in Schiotz and Goldmann readings. AB - Three thousand one hundred and fifteen paired Schiotz and Goldmann readings in persons aged 10-79 years were re-examined. There was first a drop and then a rise in IOP with increasing age. The two methods gave very similar results up to age 50. After the age of 50 Goldmann pressures rose faster than Schiotz pressures. Changes in Schiotz readings do not reliably reflect true changes in IOP over time within the same eye or between different age groups within the same population. PMID- 1636397 TI - Diffuse type alteration of the ocular wall in different eye diseases. AB - The ocular wall dimensions (thickness and volume) were measured by means of ultrasonography in 61 eyes of 61 patients with different eye diseases and 31 eyes of 31 healthy subjects with or without refractive error. The results confirmed, that in spite of the great variance in the ocular wall thickness, depending on the axial eye length, the volume of the ocular coats is constant in healthy eyes (ca. 1.65 cm3). In patients with ocular hypotony (eyes after intraocular surgery or trauma, and eyes with uveitis or with phthisis bulbi) and in patients with exophthalmus, the ocular wall was thicker and larger in volume than in the healthy control groups. In contrast, the ocular wall dimensions (thickness and volume) were smaller in patients with glaucoma. The results of the study showed that an alteration in the volume of the ocular wall implies a pathological condition of the eye, and thus ultrasound examination of the ocular wall dimensions might play a role in the diagnosis and in the follow-up of the patient. PMID- 1636398 TI - A classification for dry eyes following comparison of tear thinning time with Schirmer tear test. AB - In a double-blind study a non-invasive method of examining the stability of the precorneal tear film was used to record tear thinning time on a population of 34 independently diagnosed dry eye patients. The results were compared with those for tear output, as inferred from the standard Schirmer tear test, and a correlation coefficient of 0.20 determined. The mean tear thinning time and Schirmer results for the population sample were 6.87 +/- 2.97 sec, and 5.62 +/- 5.69 mm wetting in 5 min, respectively. From a plot of tear thinning time against Schirmer a simple classification for dry eyes can be made. A Type A with normal tear stability and low output accounting for 14.70% of the dry eyes. A Type B with low tear stability and normal output, also accounting for 14.70% of the dry eyes. A Type C with low stability (less than 9.84 sec), and low output (less than 11.31 mm wetting in 5 min) accounting for 70.60% of the dry eyes. PMID- 1636399 TI - Corneal epithelial healing under contact lenses. Quantitative analysis in the rabbit. AB - The rate of corneal epithelial healing was determined as a function of the oxygen level present at the tear-cornea interface. Oxygen levels of 1.77, 2.3, 5.3, 8.55, 10.12, and 16.45% were created over the rabbit cornea with tarsorrhaphy and various contact lenses. Full depth epithelial defects of 4.5 mm diameter were created in 6 animals for each test condition with the fellow eye serving as a control and healing in air (21.09% oxygen). The defect (radius) was measured at 24-h intervals until healing occurred. Statistically significant (p less than 0.05, paired Student t-test) delays in healing were found with oxygen levels of 8.55% and below. These delays were most profound over the initial 24 h. The healing rate with tarsorrhaphy, at the 1.77% oxygen level, over the first 24 h was 5.2 microns/h radius, only 15.2% of the paired control, 34.0 microns/h radius, healing in air (21.09% oxygen). Healing rates over the initial 24 h under contact lenses allowing 2.3, 5.3, 8.55, 10.12, and 16.45% oxygen were 6.1, 23.5, 26.5, 43.0, and 45.0 microns/h in radius, respectively. PMID- 1636400 TI - Reactive production of extracellular matrix (ECM) by corneal endothelial cells. AB - Results of experimental and histopathological studies of reactive production of extracellular matrix by corneal endothelial cells are summarized and evaluated. In anterior synechiae, epithelial ingrowth and a chronic corneal ulcer extracellular matrix was produced not only toward Descemet's membrane but also on the normally free endothelial cell surface. In some cases of anterior synechiae and cystic epithelial ingrowth, after partial separation of the new layer of extracellular matrix, recovery and regeneration of endothelial cells was possible. In diffuse epithelial invasion, extracellular matrix facilitated at the beginning the progression of epithelium over endothelium, putatively serving as a substrate; however, in longer-standing invasions endothelial cells degenerated and died. Reactive production of extracellular matrix may represent a defensive mechanism of endothelium threatened by foreign cells, tissues or materials. PMID- 1636401 TI - Amino acid incorporation in cell cultures from eyes with pseudo-exfoliation material. AB - Conjunctival tissue was removed from eyes with and without pseudo-exfoliation material during cataract surgery. Cells derived from these samples were maintained in vitro. Confluent cultures were examined by transmission electron microscopy, and non-confluent as well as confluent cultures were examined for their ability to incorporate 3H-leucine and 3H-proline into TCA-precipitated material. Cells derived from both types of samples showed deposition of extracellular matrix, and a similar incorporation of the two amino acids. It is concluded that in vitro studies allow examination of basic metabolic patterns under varying conditions, and also a search for possible differences in such functions between tissues with and without production of pseudo-exfoliation material. PMID- 1636402 TI - Indirect spectral transmission ratio measurements of the aging crystalline lens nucleus. AB - A new objective approach to characterize color and opalescence in the lens nucleus, using wavelength indexed transmission ratios (TR) is described. Transmission ratios, i.e. the transmissivity per unit lens thickness, for the whole visible spectral range (390-720 nm) were calculated using fast scanning spectral colorimetry (FSSC). The lowest transmission ratios values were obtained in the blue part of the spectrum in general and at 450 nm in particular. They inversely followed the subjectively determined LOCS II color grading. The difference between transmission ratios at the absorbed part of the spectrum (less than 500 nm) and the non-absorbed part (greater than 550 nm) also reflects the LOCS II color grading. The overall mean transmission ratios for all wavelengths in the spectrum gives an index that closely followed the nuclear opalescence grading of the LOCS II system. The transmission ratios are theoretically independent of the spectral characteristics of the incident light as long as it contains suprathreshold energies in the whole measured spectral range. PMID- 1636403 TI - Light scatter in aging and cataractous human lens. AB - We measured back light scattering of the human lens with the Lens Opacity Meter 701 in order to determine whether it can be used for objective assessment of lens opacities in various types of cataracts. One-hundred and twenty-seven eyes of 127 individuals were examined including 43 healthy volunteers in various age groups and 84 patients with cortical, nuclear, posterior subcapsular or mixed lens opacities. Almost 90% of the total variation in the light scatter values was accounted for by age in non-cataractous eyes. Mean scatter value of every cataract group was statistically significantly higher than that of age matched healthy controls (p less than 0.0001). Highest scatter values were measured in cortical cataracts while the mean values of other types of cataract were not statistically significantly different from each other. The regression between light scatter and visual acuity was statistically significant for each cataract group. However, large variation of visual acuity was found with scatter values below 60. The results indicate that the Interzeag Lens Opacity Meter is able to identify cataractous and non-cataractous eyes and discern at least advanced cortical cataracts from other types of lens opacities. PMID- 1636404 TI - Efficacy of cryotherapy for retinopathy of prematurity. AB - This is a retrospective study of the benefit of transconjunctival cryotherapy for retinopathy of prematurity (ROP) in 43 eyes of 22 infants (birth weight 716-1675 g) from July 1985 to January 1988. Nine eyes were treated at ROP stage 4A (early), 14 eyes at stage 3 plus disease, and 20 eyes at stage 3. Cryotherapy was applied to the retinal avascular zone. In 13 eyes the ridge of extraretinal fibrovascular proliferation was also treated. Two eyes with peripheral exudative retinal detachment in two quadrants had additional treatment of the area of elevated retina. Reexamination was performed at the age of 26 to 52 months (average 38 months). Regression of the ROP was found in all eyes. Seven eyes showed a lateral traction of the temporal vascular arcades, six of these eyes had a slight macular ectopia. None of the eyes progressed to stage 4B or 5. Visual acuity was 6/60 or better. Twelve children (60%) achieved 6/18 or better and 5 (25%) 6/9 or more. Our data indicate that cryotherapy for ROP grade 3 and early stage 4A prevents the progression to advanced stages. The results also imply a functional benefit of cryotreatment in infants with progressive severe ROP. PMID- 1636405 TI - Trends in cataract surgery in Milan (Italy) from 1956 to 1987. Relationship to age and visual acuity. AB - In order to test whether the mean age at cataract surgery has changed over the course of the last 30 years, a hospital series of 5443 patients undergoing cataract extraction between 1956 and 1987 is reviewed. All cases attended the same University Eye Clinic of Milan and most were resident in the same geographical area. Cases with macular or optic nerve diseases were excluded. Results show that mean age at cataract surgery progressively increased from 67.5 to 71.5 years (slope = +0.096 years of age per year, p = 0.0001) as did visual acuity at surgery (patients with visual acuity levels greater than or equal to 1/10 at time of cataract surgery rose from 3.2% to 47.9%). These results can be interpreted in terms of a change in age composition of the Italian population, improved access to health services for the elderly, and an improvement in surgical and rehabilitation techniques. PMID- 1636406 TI - Results and evaluation of high volume intracapsular cataract surgery in Nepal. AB - One thousand intracapsular cataract extractions were performed by two ophthalmologists over a 57-day period at Lahan Eye Hospital in Nepal. Ninety-nine per cent of eyes had a visual acuity of less than 3/60 at surgery. Ninety-eight per cent of eyes achieved a visual acuity of 3/60 or better with aphakic spherical correction at discharge, of which 69% had a visual acuity of 6/36 or better. In 314 eyes seen at 1-month follow-up, 88% achieved 6/18 or better with full aphakic correction. The surgical time averaged less than 10 min and the cost of disposables less than pounds 1 per operation. PMID- 1636407 TI - Acceptability of aphakic correction. Results from Karnali eye camps in Nepal. AB - Of 235 aphakic patients followed for 1-10 years in Karnali, Nepal, 23% were wearing aphakic spectacles in good condition, 25% had lost or broken their spectacles, 31% were wearing scratched or repaired spectacles, 5% never received spectacles and 16% were dissatisfied, of which 84% still had good phakic vision in the fellow eye. Of 303 aphakic eyes, 89% had a visual acuity of 6/60 or better with +10 spherical correction and 7.3% (22 eyes) were blind (V/A less than 3/60); of which the major causes were pre-existing posterior segment disease unrelated to the cataract operation. PMID- 1636408 TI - Conjunctivo-cytologic changes in response to intense physical activity. AB - Possible cytological changes of the conjunctival fluid in association with physical activity were studied in a series of 39 subjects practising aerobics, 22 football players, and 29 marathon runners by means of the quantitative pipette method and the qualitative stix method of Norn. The first group was only examined after exercise, the two latter both before and after. No significant changes were detected in the cytologic composition of the conjunctival fluid in association with exercise. PMID- 1636409 TI - Is beta-lactamase-producing bacteria of major importance for unfavourable development of acute otitis media? PMID- 1636410 TI - Ear deformities in mandibulofacial dysostosis. AB - Bilateral conductive deafness is common in mandibulofacial dysostosis with or without atresia of the external auditory meatus. This deafness is due to a wide range of deformities of the ossicular chain associated with a characteristic reduction in the size of the middle ear cavity. The inner ear is only occasionally affected. This study describes findings of experimentally induced malformations of the ears in laboratory animals which are compared to the clinical, radiological and surgical findings from 14 patients with mandibulofacial dysostosis (Treacher-Collins syndrome). PMID- 1636411 TI - Extended middle ear drug delivery. A new concept; a new device. AB - The authors present the development of a new device that consists of a biodegradable support matrix incorporating a therapeutically releasable amount of ampicillin. This device is in an insertable shape that allows easy placement into the middle ear. Once in the middle ear cavity it expands, contacts the walls, and provides extended sustained release of ampicillin. In vitro studies over three months documented the consistent release of therapeutically effective levels of ampicillin. In vivo efficacy was demonstrated in the cat otitis media induced by eustachian tube obstruction. Cultures of normal cat middle ear cavities prior to obstruction revealed no microflora. Cultures after obstruction of the middle ears of animals treated with this device had no growth of bacteria as early as one week after obstruction (10 out of 12 cats). The contralateral untreated ears became culture negative at two weeks post obstruction, suggesting that the effect of the device is not limited to the treated ear. Histopathological studies showed the effect of the device as early as one week post obstruction in treated ears and after two weeks in the contralateral ear. Both ears became normal at three months, while obstructed untreated animals (controls) developed chronic irreversible otitis media changes. In addition, histopathological findings documented a lack of inflammatory reaction from the device itself, and its capacity of being biodegradable. Topical extended middle ear drug delivery can become a significant form of treatment for middle ear disease and has the potential of being useful as a source for inner ear drug delivery. PMID- 1636412 TI - Changes of the middle ear mucosa induced by untreated and penicillin V treated experimental pneumococcal otitis media. PMID- 1636413 TI - Lymphocyte-mucosal interaction of the middle ear mucosa. AB - The middle ear mucosa possesses immunologic features similar to those of the peripheral mucosa sites in the common mucosal immune system and after mucosal immunization, antigenspecific IgA-forming cells appear in the inflamed mucosa of the tympanic cavity. Recent investigations suggest that lymphocyte migration to lymphoid tissues is regulated by lymphocyte-high endothelial venules (HEV) interaction. However, the lymphocyte migration mechanism to the middle ear mucosa is still unclear. We investigated whether or not organ-specific determinants which lymphocytes bind with are present on the middle ear mucosa by in vivo and in vitro lymphocyte adherence assays by using fluorescein-labeled lymphocytes from various lymphoid tissues. Many lymphocytes from Peyer's patches and hilar lymphnodes adhered on the inflamed middle ear mucosa with or without mucosal immunization, while these cells were not found on the normal tympanic mucosa. The number of the cells was smaller than that in the gastrointestinal mucosa. Lymphocyte adherence to the middle ear mucosa was not suppressed by anti-T cell antibody. These findings suggest that the middle ear mucosa possesses organ specific mucosal determinants which B-lymphocytes selectively bind with, and that those determinants which regulate lymphocyte migration to the middle ear mucosa differ from those of other mucosae in the gastrointestinal tract. PMID- 1636414 TI - Genetically induced inner ear degeneration. A structural and functional study. AB - The jerker mouse mutant has an autosomal recessive mutation, which in homozygotes results in early postnatal degeneration of the sensory epithelia in both the cochlea and vestibulum. An age-related consecutive functional and morphological analysis of the cochlea has been performed in homozygote (je/je) and heterozygote (je/+) jerker mice. Cochlear function was determined with auditory brainstem response (ABR) technique. Heterozygotes were regularly tested to a final age of 12 months. With increasing age they displayed ABR threshold shifts which were of about the same magnitude in the whole frequency range tested (2-31.5 kHz) but extremely variable in individual animals. From homozygote jerker mice no ABR could be elicited. There was a similar morphologic pattern of cochlear degeneration in both homozygote and heterozygote jerker mice affecting primarily the stereocilia and cuticular plate in both outer and inner hair cells. In homozygotes these changes were found in very young animals but in heterozygotes they did not become evident until later in life. All parts of the cochlea became simultaneously affected, that means there was no topographical gradient in the pathological course. The ABR thresholds in 12 months old heterozygotes were correlated semiquantitatively to hair cell pathology in the cochlea. The functional and morphological changes in heterozygotes probably reflect a random influence of the jerker gene vis-a-vis the wild type of gene. PMID- 1636415 TI - T cell subsets in round window membrane after middle ear immunostimulation. AB - In secondary middle ear immune response, kinetics of immunocytes, especially T cell subsets, was examined in the round window membrane (RWM) using immunohistochemical methods. Healthy BALB/c mice and keyhole limpet hemocyanin (KLH) antigen were employed in this study. The inflammatory responses of the RWM and middle ear were investigated after antigen challenge into the middle ear bulla. We used antibodies against murine macrophages and granulocytes (anti-Mac 1), murine helper/inducer T cells (anti-Lyt-1 and -L3T4), murine suppressor/cytotoxic T cells (anti-Lyt-2), murine interleukin-2 receptor (7D4), murine immunoglobulins (anti-IgG, -IgM and -IgA) and KLH. In the RWM and middle ear mucosa, inflammatory cells were observed at 6 hours, peaking on days 3-7, whereas these cells were rarely seen in the scala tympani of the basal turn. Luminal effusion with an enormous infiltration of inflammatory cells, which consisted mainly of Mac-1 cells, IgG cells and IgM cells, was observed in the middle ear cavity on days 1-7 post antigen challenge. In the inflamed RWM, Mac-1 cells were the predominant cell type followed by helper T cells, interleukin 2 receptor positive cells and IgG positive cells, though IgM, IgA and Lyt-2 positive cells were rarely observed after antigen challenge. Our results suggest that RWM has the ability to protect inner ear by cellular immune response through activated helper T cells and Mac-1 cells. PMID- 1636416 TI - The microwave oven in temporal bone research. AB - The microwave oven has recently been introduced in morphological research. It can be used for virtually all procedures in histological processing; fixation, dehydration, embedding, staining, immunotechniques, and the techniques used for electron microscopy. Here we report that the microwave oven histoprocedures also have several advantages in temporal bone research on animals. The microwave oven has been tested for (i) fixation, (ii) decalcification, (ii) staining of semithin plastic sections. The microwave oven procedures are time-saving and results in an excellent preservation of the tissues. The microwave histoprocessing should also be applicable to temporal bone research in human. PMID- 1636417 TI - The role of type I allergy in secretory otitis media and mast cells in the middle ear mucosa. AB - To clarify the role of type I allergy in the etiology and pathogenesis of secretory otitis media (SOM), clinical and experimental studies were done. The distribution of mast cells in the tubotympanum of normal and developing guinea pigs was also investigated. Our clinical study revealed that the ratio of complications of nasal allergy (NA) in 222 SOM-young children is 42%, while that of SOM in 259 NA-young children is 35%. These ratios were significantly higher than those seen in control group which consists of 104-children randomly selected from a kindergarten and elementary school. Findings of our animal experiment showed that the eustachian tube is involved, both functionally and morphologically, in type I allergic reactions of the nose. The tubal dysfunction evoked by nasal allergic reactions was transient, not culminating in middle ear effusion (MEE). However, this dysfunction interferes with the clearance of MEE. Our studies suggest that type I allergic reactions of upper respiratory tracts are factors indicative of a chronic state of disease, rather than a cause of SOM. In adult guinea pigs, the density of mast cells was highest in the pharyngeal orifice of the eustachian tube. The density was higher in the adult than in developing guinea pigs. Mast cells in the middle ear mucosa appeared in areas covered by ciliated epithelia or areas richly vasculized. The results of our investigation suggest that mast cells distribute in the tubotympanum responding to continuous stimuli to the tubotympanic cavity. PMID- 1636418 TI - Permeability of arachidonic acid metabolites through the round window membrane in chinchillas. AB - Our previous studies showed that samples of middle ear effusion contain high concentrations of arachidonic acid metabolites (AAMs); both prostaglandins (PGs) and leukotrienes (LTs). Since abnormal levels of AAMs in the perilymph seem to be associated with salicylate ototoxicity and the round window membrane (RWM) is the most likely route of entry from the middle ear to the inner ear, it would be important to know the permeability of AAMs through the RWM. Permeability of AAMs was determined by applying labeled and standard representatives AAMs on the RWM and counting radioactivity or measuring concentrations of AAMs in perilymph at different time intervals. Using chinchillas as experimental animals, samples of perilymph were obtained through a fenestration made at the helicotrema of the cochlea after 0.5, 1, 2, and 4, hours from placing tritiated or standard PGE2, 6 keto-PGF1 alpha, LTB4, LTC4 and 15-hydroxyeicosatetraenoic acid (HETE) over RWMs. Radioactivity in the perilymph was determined by a scintillation counter and concentrations of AAMs were measured by reverse phase high performance liquid chromatography (RP-HPLC) and radioimmunoassay. AAMs, which are twenty carbon fatty acids, were found to cross the RWM readily. Radioactivity and concentrations of AAMs in perilymph were detected in 30 minutes and peaked by one hour from the application of AAMs on the RWM. The results of this study suggest that AAMs such as PGs and LTs present in the middle ear fluid can cross the RWM readily and enter into the perilymphatic space of the cochlea. Sensorineural hearing loss observed in chronic otitis media could be mediated by PGs and LTs in the middle ear effusion crossing over to the inner ear through the RWM. PMID- 1636419 TI - Effect of exogenous arachidonic acid metabolites applied on round window membrane on hearing and their levels in the perilymph. AB - Our previous studies revealed that treatment with sodium salicylate or indomethacin caused hearing loss, a decrease in prostaglandin (PG) levels, and an increase in leukotriene (LT) levels of the arachidonic acid (AA) cascade in the perilymph. We suspected that decreased PG-levels and/or elevated LT-levels in the inner ear may be responsible for the salicylate ototoxicity. In order to test this hypothesis, effects of exogenous treatments with PGs, PG-analog, LTs, and other lipoxygenase products on hearing and levels of AA metabolites in the perilymph were studied in chinchillas. Cyclooxygenase products, PGI2, 6-keto-PGF1 alpha, Iloprost (PGI2 analog), PGE2, and LTB4, LTC4, and 15 hydroxyeicosatetraenoic acid (15-HETE) in the lipoxygenase products in the dose of 150 ng were applied on the round window membrane (RWM); cochlear function tested by auditory brainstem response (ABR) and samples of perilymph were collected at 0.5, 1, 2, and 4 hours after the application. Samples of perilymph were assayed for all spectra of AA metabolites by high performance liquid chromatography (HPLC) and radioimmunoassay (RIA). PG-treated animals developed minimal or no hearing loss. LT-treated animals exhibited hearing loss of 20 to 40 dB, peaking at one hour after the treatment. Elevated levels of arachidonic acid metabolites were measured in the perilymph of the ears treated with respective AA metabolites, with peak levels at one hour from the application. The findings of this study indicate that hearing loss can be induced by altered levels of PGs or LTs in the perilymph. This is another strong evidence that salicylate induced ototoxicity can be mediated by abnormal arachidonic acid metabolism in the inner ear. PMID- 1636420 TI - Laminin in the endolymphatic sac and vestibular endorgans of developing chick embryos. AB - The expression of laminin was analyzed in the vestibular endorgans of chick embryos using immunohistochemical methods. The basement membrane of the otocyst in the 5-day-old chick embryo was positive for laminin. In the 9-day-old chick embryo, the basement membrane of the macula of the saccule and utricle was positive, but the crista ampullaris showed a very weak positive reaction. The basement membrane of the endolymphatic sac in the 11-day-old chick embryo was strongly positive. These results suggest that laminin may be an essential substance with regard to the pathology of the vestibular endorgans. Moreover, the uneven distribution of laminin suggests that the basement membrane plays a role whose importance is yet to be determined in the physiology of the inner ear. PMID- 1636421 TI - The levels of IL-1 beta in human middle ear effusions. AB - Inflammatory mediators retained in middle ear effusion (MEE) during otitis media are important in influencing the clinical outcome of this disease. Interleukins, important immunomodulatory proteins, undoubtedly influence this inflammatory response. In our present study we analyzed 74 human middle ear effusion samples for interleukin-1 beta (IL-1 beta). Those effusions classified as purulent (POM) contained the highest levels, while those classified as serous (SOM) had the lowest. A statistically significant correlation between age and level of IL-1 beta was observed, namely, the younger group had higher levels of IL-1 beta than the older group in MOM and POM samples. The results of this study show that IL-1 beta is present in human middle ear effusion of otitis media and suggest that IL 1 beta may be an important mediator involved in the disease processes of otitis media. PMID- 1636422 TI - The round window membrane under normal and pathological conditions. AB - Current research and an overall review of round window membrane studies is presented and the concepts that have evolved from these studies are described. Ultrastructural studies of the round window membrane of rodents, felines, and primates disclosed three basic layers: an outer epithelium lining the middle ear, a middle core of connective tissue, and an inner epithelium bordering the inner ear. Morphological evidence suggests that the membrane participates in: (a) the release of mechanical energy supplied by the ossicular chain to the labyrinthine fluids; (b) an alternative route for sound energy to enter the cochlea; (c) secretion into and absorption from perilymph; and (d) the defense system of the middle and inner ears. Permeability of the round window is considered an accident and not a function of the membrane. The complications of permeability (potential ototoxicity) and its potential usefulness (drug delivery) are discussed. PMID- 1636423 TI - Round window membrane rupture and inner ear damage due to barotrauma. AB - We investigated inner ear barotrauma in humans and in guinea pigs. The shapes of audiograms in patients with inner ear barotrauma were varied, such as high-tone hearing loss, profound loss, low-tone hearing loss, dip type, etc. In inner ear barotrauma in guinea pigs, damage to the organ of Corti was observed in various parts of the cochlear turns in varying severity. Some animals showed rupture of the round window membrane and/or reduction of endocochlear potential following the barotrauma but the rupture healed and EP recovered spontaneously within one week. We consider that irreversible hearing loss in patients with inner ear barotrauma depends on the extent of damage to the organ of Corti. PMID- 1636424 TI - Cochlear effects of hyaluronan applied on ruptured round window membrane. AB - The purpose of the present experimental study was to determine whether hyaluronan (hyaluronic acid, HYA) exerts any functional or morphologic ototoxic effects on the cochlea when in contact with a ruptured round window membrane (RWM). HYA in 1% solution was applied in the round window (RW) niche of rats (n = 6) prior to perforating the RWM. In a control group (n = 6) the RWM was perforated alone. Cochlear functioning and structure were monitored by recording auditory brainstem responses (ABRs) at 2-31.5 kHz and by scanning electron microscopy. Perforation of the RWM alone resulted in immediate loss of ABR thresholds between 6 and 31.5 kHz in 2 of 6 animals. Similar results were obtained after application of HYA into the RW niche and subsequent RWM perforation. In both treatment groups the mean ABR thresholds and mean latencies for wave II at the ABR threshold returned to the pre-surgical (normal) range after 2 months. Also with respect to the cochlear morphology the results in both treatment groups were alike including minor structural changes in hair cell stereociliae but no loss of hair cells. It is concluded that HYA, when instilled into the middle ear with the inner ear opened, is free from cochlear ototoxic effects. Our present findings enhance the potential usefulness of HYA in otosurgery, even in cases when the inner ear has been opened and/or when one wishes to protect the inner ear. PMID- 1636425 TI - Pseudomonas aeruginosa exotoxin A and Haemophilus influenzae type b endotoxin. Effect on the inner ear and passage through the round window membrane of the chinchilla. AB - Pseudomonas aeruginosa exotoxin A was applied to the round window membrane of the chinchilla in concentrations ranging from 1 microgram/ml to 1 mg/ml. Haemophilus influenzae type b endotoxin (45,000 endotoxin units/ml) was applied in the same way. Five animals were also subjected to blocking of the Eustachian tube, 3 to 8 months earlier, resulting in serous otitis media and exotoxin A (1 mg/ml) was applied into the round window niche of these animals. Effects on the inner ear was recorded with quantitative morphology (hair cell counting) and electrophysiologically (action potential threshold measurements) 4 weeks after application of exotoxin A. Concentrations of exotoxin A in perilymph was measured with ELISA and concentration of endotoxin in perilymph was measured with Limulus Amoebocyte Lysate and Quantitative Chromogenic Limulus Amebocyte Lysate. Four weeks after application of exotoxin A at a concentration of 10 micrograms/ml severe inner ear damage could be demonstrated. No inner ear damage was demonstrated when lower concentrations were used. Passage into the inner ear could only be demonstrated after exposure of the round window membrane to an exotoxin A concentration of 1 mg/ml. Round window membranes affected by chronic inflammation were shown to be less permeable to exotoxin A, thus indicating that thickening of the round window membrane may have a protective effect on the inner ear. A low passage rate into the inner ear was demonstrated after endotoxin exposure. It may be concluded that small amounts of exotoxin A passing through the round window membrane may cause inner ear damage. The passage rates, however, for both exotoxin A and endotoxins are low. PMID- 1636426 TI - Undecalcified temporal bone morphology: a methodology useful for gross to fine observation and three-dimensional reconstruction. AB - Using a novel method of cutting undecalcified temporal bone specimens, quantitative structural analysis in the human and the Japanese monkey was undertaken. One millimeter thick serial slices made from unembedded temporal bones retained fine structure. Therefore, gross to fine observation could be performed systematically at the macroscopic, light, scanning, and transmission electron microscopic levels. The entire temporal bone three-dimensional reconstruction was completed from embedded sections; consequently, the volume of the tubotympanum and air cell system could be calculated. Available methods by embedding, tungsten carbide sectioning, grinding, and microwave irradiation for decalcification were also examined. These morphologic studies suggest that these novel methods offer timesaving advantages over any presently available techniques, and allow for elucidation of temporal bone morphology with only a few specimens. PMID- 1636427 TI - Repeated measurements of compound action potential: evaluation of the ototoxicity of otic drops. AB - Consecutive CAP threshold shifts were studied in chinchillas following round window application of Cortisporin Otic Suspension for 10 minutes. A marked deterioration in CAP threshold was observed at 24 hours following otic application but these threshold shifts were reversible at lower frequencies. The shifts were progressive at higher frequencies at the 4 week measurement. The progressive high frequency loss with recruitment and with normal EP levels implies some hair cell dysfunction due directly to Cortisporin Otic Suspension ototoxicity and/or secondarily to middle ear inflammatory reactions to the otic. Short-term studies of ototopical drugs may result in misleading assessments as to the pattern and degree of ototoxicity. Long-term (i.e., one month or longer) studies are recommended for accurate ototoxicity assessment. PMID- 1636428 TI - Effect of round window membrane application of salicylate and indomethacin on hearing and levels of arachidonic acid metabolites in perilymph. AB - Our previous studies revealed that systemic salicylate-induced ototoxicity is associated with altered levels of arachidonic acid metabolites (AAMs) in the perilymph. In order to eliminate the possibility of systemic toxic effects of salicylate when it is given parenterally, an animal model of salicylate-induced ototoxicity was developed by applying it on the round window membrane (RWM). Using chinchillas as experimental animals, sodium salicylate (150 micrograms) or another nonsteroidal anti-inflammatory drug (NSAID), indomethacin (20 micrograms) was applied on the RWM, cochlear function was determined by auditory brainstem response (ABR) and perilymph assayed for AAMs both prostaglandins (PGs) and leukotrienes (LTs) by high performance liquid chromatography (HPLC) and radioimmunoassay (RIA) at different time intervals. When salicylate or indomethacin was applied on the RWM, dose-dependent ABR threshold losses of 20 to 50 dB was observed in 1 to 2 hours associated with decreased concentrations of 6 keto-PGF1 alpha and elevated levels of LTs. The hearing loss recovered to normal threshold over a period of 8 hours. The control group showed no hearing loss or any change in PG or LT-levels in the prilymph. The results of this study suggest that the method of inducing ototoxicity by applying salicylate or indomethacin on the RWM seems to be a reliable method for avoiding systemic toxicity of the parenteral treatment method and that ototoxicity induced by salicylate or indomethacin may be mediated by decreased PGs and elevated LTs. PMID- 1636429 TI - Are glucocorticoids in ear drops ototoxic? AB - Ototopical drugs such as antiseptics, antibiotics and solvents can have an ototoxic potential. These substances are often combined with an anti-inflammatory steroid of which hydrocortisone is one of the most commonly used. Little is known of possible adverse effects on the inner ear of hydrocortisone. From animal experiments it has been shown that this drug applied in the round window niche will impair the ABR thresholds in the high frequency range. The ototoxic potential of glucocorticoids will be discussed and questioned. PMID- 1636430 TI - Middle ear problems in childhood. AB - No single factor is as yet known which could be used to predict the possible development of rAOM in infants and children. However, some circumstantial evidence can be seen. Thus, an AOM debut before the age of six months in a child with a family history of recurrent otitis indicates a clear risk of multiple recurrent episodes. Other 'intrinsic factors' speaking in favour of rAOM are low concentrations of specific IgG antibodies against pneumococcus type 6A in cord serum and a presence of the hereditary HLA-antigen A2 on the surfaces of white blood cells. Extrinsic factors' such as type of day-care, passive exposure to smoking at home and poor housing seem to increase the risk but do probably not constitute the definite cause of rAOM. PMID- 1636431 TI - Secretory otitis media and high-frequency hearing loss. AB - 31 children (mean age 13 years; range 8.5-17.2) who had been tympanostomy treated for SOM during the years 1977-1980 were invited for follow-up examination. 29 normal age peers were enrolled as controls. The test battery included clinical pneumotoscopical examination and conventional pure-tone audiometry as well as air conduction and electric bone-conduction high-frequency audiometry. High-frequency hearing losses (6-18 kHz) were found as sequels of SOM. The median threshold difference between the SOM group and the controls varied from 0 to 10 dB depending on the frequency. The hearing losses were considered to be of the conductive type, and probably related to changes in the tympanic membrane and the middle ear caused by SOM. On the other hand, we found also sensorineural hearing losses suggesting lesion at the cochlear level. PMID- 1636432 TI - Oncocytic neoplasms of the thyroid gland. AB - Among well differentiated thyroid tumors, oncocytic neoplasms feature a distinctive set of clinical, morphologic and biologic characteristics, some of which have been a matter of controversy. The world literature on this subject has been reviewed to show that: 1) Morphology accurately predicts the behavior of Hurthle cell tumors assuming that the specimen has been adequately sampled; 2) Capsular and/or vascular invasion is the sine qua non condition for a diagnosis of malignancy; 3) "Indeterminate" or "possibly malignant" categories are useless because in the absence of invasion these neoplasms almost invariably behave in a benign fashion; 4) Among cases histologically classified as malignant, a clinically aggressive behavior is to be expected in a high percentage of cases; 5) Size alone cannot be used as a criterion of malignancy; 6) Less than total thyroidectomy provides an adequate treatment for histologically benign tumors; aggressive surgical procedures (i.e. total thyroidectomy) do not diminish the incidence of metastasis; 7) Analysis of DNA content may be helpful in defining subsets of patients with Hurthle cell carcinomas having a particularly poor prognosis; 8) Mitochondrial and/or nuclear DNA abnormalities probably play an important role in the cellular alterations which characterize the phenotype of oncocytes. PMID- 1636433 TI - Pathological effects of maternal hypoglycemia on fetal development in cats. AB - The pathogenesis of fetal brain damage caused by acute maternal hypoglycemia was investigated experimentally in cats: profound hypoglycemia (blood glucose concentration: less than 30 mg/dl) was induced in 12 pregnant cats at various stages of gestation by intravenous bolus injections of insulin. Maximal hypoglycemia was attained within 2-3 h, although the grade and duration in individual cats varied. The EEGs of all of seven maternal cats examined showed an increased frequency of slow high-voltage waves as hypoglycemia progressed, eventually becoming flat in 3 for a maximum period of 20 min. Some fetuses showed severe neuropathological changes, such as infarction or intrauterine death. Subventricular softening, cortical hemorrhage and ischemic neuronal changes also occurred, being distributed symmetrically in the parasagittal areas of the cerebrum, basal ganglia, thalamus and tegmentum of the brainstem. In general, these pathological changes were more marked in fetuses and neonates than in the maternal cats, in which only ischemic neuronal changes were present, and may have been due to fetal systemic hypotension and cerebral ischemia induced by hypoglycemia. In maternal cats, the distribution of neurons showing ischemic changes was widest in the cerebral cortex, and some were also present in the dentate gyri of the hippocampus. Moreover, ultrastructural examination of the ischemic neurons in maternal cats, unlike those of the fetuses, showed no mitochondrial swelling. Therefore, the distribution and ultrastructural nature of the ischemic neurons found in the maternal cats were considered to be characteristic of hypoglycemia, as proposed by Agardh et al. (1980). PMID- 1636434 TI - Glomerulonephritis induced by murine chronic graft-versus-host reaction. AB - Severe glomerulonephritis was induced successfully in (B10 x DBA/2)F1 (BDF1) mice by injection of parental DBA/2 lymphoid cells. The mice manifested typical nephrotic syndrome dying around 10 weeks post injection. Electron microscopical examination demonstrated electron dense deposits first in the mesangial matrix, then in the subepithelium compatible with immune complex glomerulonephritis. Subendothelial deposits were not observed. Immunofluorescent study revealed IgG deposition in the capillary wall and IgM in the mesangium early in the process. As the lesion progressed, both IgG and IgM were present in the mesangial area and along the capillary wall. Some glomeruli showed segmental mesangiolysis, suggesting that altered mesangial cells have a role in the development of glomerular change, which together with rise in serum anti-DNA antibody titer suggest that autoantibodies promote the glomerular lesions in this model system. PMID- 1636435 TI - Malignant lymphomas of the nasal cavity and paranasal sinuses. A clinicopathologic and immunohistochemical study. AB - The clinicopathologic and immunohistological features of 20 Japanese patients with non-Hodgkin's lymphomas (NHLs) limited to the sinonasal area were studied using a broad panel of T- and B-cell markers on paraffin-embedded and fresh frozen tissue. All cases showed a diffuse growth pattern. Nine cases were B-cell lymphomas (immunoblastic n = 4, centroblastic n = 3, immunocytoma n = 1, centrocytic n = 1), and nine were T-cell lymphomas (pleomorphic medium and large cell n = 8, angioimmunoblastic n = 1). In two cases, the cell lineage could not be determined. No morphologic features of angiocentric/angiodestructive lymphoproliferative lesions or lymphoepithelial lesions in ductal or glandular epithelium were seen in our series. Eight (89%) of the nine T-cell tumors and four (44%) of the nine B-cell neoplasms involved both the nasal cavity and paranasal sinuses. Six of the nine T-cell neoplasms showed a clinical presentation of rhinitis, whereas all of the B-cell neoplasms showed tumor masses in the nasal cavity and/or paranasal sinuses. The two-year survival rate for T cell lymphomas was poorer than that for B-cell lymphomas. The five-year survival of patients with NHLs involving both the nasal cavity and paranasal sinuses was also poorer than that of patients in whom NHLs were limited to the nasal cavity. PMID- 1636436 TI - Distribution of antigens detected with MB1, MB2 and MB3 on non-hematopoietic human organs and various tumors. AB - We have examined the distribution of antigens detected by MB1, MB2 and MB3 on non hematopoietic normal human tissues and various types of benign and malignant tumors. MB1 and MB2 reacted with various organs, such as the epithelium of various glands, smooth muscle cells, vascular endothelial cells, and peripheral nerve tissue. The distributions of these two antibodies were essentially identical. Reactivity with MB3 was confined to the ductal epithelium of salivary glands, the pancreas, and sweat glands, and the cortex of the adrenal gland. Immunoblotting analysis demonstrated that MB1 and MB2 reacted with a few bands of an extract of myometrial cytoskeletal fraction and salivary gland cytosol fraction, whereas MB3 failed to show any bands on these materials. The reactivities of MB1 and MB2 with various neoplasms were similar to those in normal organs, with slight variations of staining pattern and preponderance in well differentiated tumors. Exceptionally, carcinoid tumor and small round cell tumors, such as small cell carcinoma or neuroblastoma, were not reactive with MB1 and MB2. MB3 reacted with several cases of well differentiated benign and malignant epithelial tumors in various organs, and exceptional cases of malignant schwannoma and glioma. These results indicate that the antigens detected by MB1 and MB2 are distributed broadly on non-hematopoietic normal organs, whereas those detected by MB3 are confined to exceptional cases of epithelial and non epithelial tumors. Thus, although the use of MB1, MB2 and MB3 is of little value for differential diagnosis of various tumors, these three antibodies may be useful for determining of the origin of some tumor types. PMID- 1636437 TI - Meningeal hamartoma of the scalp. A variant of primary cutaneous meningioma. AB - A case of meningeal hamartoma of the scalp is reported. A 15-year-old girl was admitted complaining of scalp nodules in the midline occipital region. A midline skull defect was found under the nodular lesions. Histologically, the mass had a fibrocollagenous tract extending to the dura and showed an admixture of mature adipose tissue, small vessels, strands of fibrocollagenous tissue, and scattered foci of meningocytes. Immunohistochemically, the meningocytes desmosomes, interdigitating processes, and intermediate filaments. The patient's brother also had the meningeal hamartoma of the scalp. Meningeal hamartoma as a variant of primary cutaneous meningioma is extremely rare, and this is the first report of such a case in Japan. PMID- 1636438 TI - Primary mesenchymal chondrosarcoma of the lung. A case report with immunohistochemical and ultrastructural studies. AB - A case of primary pulmonary mesenchymal chondrosarcoma is reported. The tumor occurred first in the lower lobe of the right lung of a Japanese female aged 45. Three years after the first operation it metastasized to the upper lobe of the left lung. The tumors were highly cellular and composed of undifferentiated mesenchymal cells and interspersed islands of well-differentiated cartilaginous tissue. Immunohistochemistry failed to detect S-100 and vimentin in the undifferentiated cells. In contrast, Leu-7 and blood coagulation factor XIIIa were positive in these cells. Electron microscopically, undifferentiated mesenchymal cells had narrow cytoplasm with sparsity of organelles, but no intermediate-sized filaments were detected. In the transitional areas between undifferentiated cells and cartilaginous components, thin intracytoplasmic filaments were sometimes observed in the tumor cells. The differentiation toward cartilaginous cells of undifferentiated mesenchymal cells was suggested by immunohistochemistry and electron microscopy. This is the first case of mesenchymal chondrosarcoma occurring in the lung with long-term follow-up. PMID- 1636439 TI - Inflammatory pseudotumor of the spleen. Report of a case with an immunohistochemical study. AB - A 81-year-old Japanese man with a splenic inflammatory pseudotumor is described. The pseudotumor was unchanged in size after one year of observation. Macroscopically, the lesion was a firm well-circumscribed 5.5 x 5 x 5 cm mass showing a yellowish-white cut surface. Histologically, it was composed of abundant mixed inflammatory infiltrates, predominantly UCHL-1(+) T and L26(+) B lymphocytes, plasma cells containing various immunoglobulin subtypes, and S-100 protein(+), and lysozyme and NCA(+) histiocytes, with a sclerotic stroma. Small numbers of eosinophils, neutrophils and foamy macrophages were admixed. The patient has remained disease-free for 14 months after splenectomy. Only ten splenic inflammatory pseudotumors have been reported in the literature. This paper adds an additional case, together with details of immunohistochemical polyclonality of each inflammatory cell population, confirming that this disease is a nonspecific inflammatory change. PMID- 1636440 TI - Rhabdomyosarcoma with focal cartilaginous differentiation (malignant mesenchymoma) of the inferior vena cava. AB - A sarcoma arising from the inferior vena cava occupied the entire lumen of the inferior vena cava, right atrium, hepatic veins and common iliac veins. Its histological appearance was non-specific sarcoma, except for the presence of a few rhabdomyoblasts and some immature cartilaginous tissue. Immunohistochemically, some tumor cells were positive for myoglobin, desmin, HHF 35, and vimentin. Electron microscopy revealed that some tumor cells contained myofilaments and Z bands in the cytoplasm, which are characteristics of rhabdomyosarcoma. The tumor was diagnosed as rhabdomyosarcoma with focal cartilaginous differentiation (malignant mesenchymoma) of the inferior vena cava. PMID- 1636441 TI - The influence of high salt intake and/or chronic blood volume expansion on renin angiotensin system in Brattleboro rats. AB - The influence of chronic saline drinking and/or DOCA-salt treatment on plasma renin activity and renal renin concentration was studied in vasopressin-deficient homozygous (DI) Brattleboro rats and their vasopressin-secreting heterozygous (non-DI) littermates. The activity of renin-angiotensin system (RAS) can be suppressed even in the absence of vasopressin under the conditions of a sufficiently high salt intake that is achieved in DI rats by consumption of 0.6% saline instead of water. An almost complete RAS suppression in both plasma and kidney was observed in young animals in which high salt intake induced not only blood volume expansion but also blood pressure elevation, i.e. in mildly hypertensive unilaterally nephrectomized saline drinking DI rats as well as in moderately hypertensive DOCA-salt treated DI rats and in non-DI rats with a severe DOCA-salt hypertension. Our results indicate that intravascular expansion and blood pressure changes are important factors for the modulation of plasma and renal renin activity even in the absence of vasopressin. PMID- 1636442 TI - Is the mean power frequency shift of the EMG a selective indicator of fatigue of the fast twitch motor units? AB - During repeated maximum isokinetic contractions parallel decreases in output and the mean power frequency (MPF) of the electromyogram (EMG) occur, followed by stable levels (the endurance level). This study aimed to investigate if hypoxia of the plantar flexors will result in a shift in MPF during the endurance level. Mechanical performance and simultaneous surface EMG activity of three plantar flexors (m. soleus, m. gastrocnemius medialis and m. gastrocnemius lateralis) were recorded during repeated isokinetic plantar flexions at 1.05 rad s-1 in 10 healthy women. The study consisted of two tests with 14 days in between: (1) a maximum test consisting of 125 maximum plantar flexions. After 100 contractions, using a tourniquet, a relative ischaemia (hypoxia) was induced. (2) a submaximum test performed at the level established between contractions 70-100 of the maximum test, consisting of 125 plantar flexions. During the maximum test mechanical performance output, the signal amplitude (RMS) of the EMG and the MPF decreased in parallel during the initial 50 contractions followed by stable levels during the subsequent 50 contractions. When hypoxia was induced decreases in mechanical performance and RMS appeared without significant decreases in MPF. The present study indicates that the MPF shift is mainly sensitive to biochemical changes in the type 2 fibres. Hypoxia mainly located to the type 1 fibres will not be detected using the MPF variable. PMID- 1636443 TI - Splanchnic and renal vasoconstrictor and metabolic responses to neuropeptide Y in resting and exercising man. AB - The local clearance of neuropeptide Y (NPY) and whether NPY influences splanchnic and renal metabolism in man have not been investigated previously. The influence of NPY on splanchnic and renal blood flows at physiologically elevated levels has also not been investigated. The effects of a 40-min constant NPY infusion (3 pmol kg-1 min-1) at rest and during 130 min of exercise (50% of VO2max) were studied in six healthy subjects and compared with resting and exercising subjects receiving no NPY. Blood samples were drawn from arterial, hepatic and renal vein catheters for the determination of blood flows (indicators: cardiogreen and para aminohippuric acid [PAH]), NPY, catecholamines, glucose, lactate and glycerol. NPY infusion was accompanied by: (1) significant fractional extraction of NPY like immunoreactivity (NPY-Li) by splanchnic tissues at rest (58 +/- 5%) and during exercise (53 +/- 6%), while no arterial-venous differences could be detected across the kidney; (2) a reduction in splanchnic and renal blood flows of up to 18 and 13% respectively (P less than 0.01-0.001) at rest without any additional changes during exercise; and (3) metabolic changes as reflected in: (a) a more marked fall in arterial glucose during exercise compared to the reference group (P less than 0.05); (b) a 35% lower splanchnic glucose release (P less than 0.01) during exercise due to diminished glycogenolysis (P less than 0.01); and (c) a lower arterial lactate level (18% P less than 0.05) together with unchanged splanchnic lactate uptake during exercise, suggesting reduced lactate production by extrahepatic tissues. The disappearance of plasma NPY-Li after the infusions was biphasic with two similar half-lives at rest (4 and 39 min) and during exercise (3 and 43 min). PMID- 1636444 TI - Pro-oxidant effects of normobaric hyperoxia in rat tissues. AB - Rats were exposed to 100% O2 atmosphere for 12, 36 or 48 h, and their lungs, brain, liver and kidneys were studied for signs of oxidative damage. Oxidative damage at molecular level was estimated by: (1) the appearance of conjugated diene double bonds and (2) the amount of fluorescent chromolipids in lipids extracted from tissues. As important intracellular regulators of oxidative stress, the response of enzymes detoxifying reactive oxygen species was also studied. Macroscopically, the brain and the lungs were most susceptible to oxygen induced effects. As an indication of oxidative tissue damage, hyperoxia caused accumulation of fluorescent chromolipids in brain and lung tissues, whereas diene conjugation did not reveal any signs of lipid peroxidation. Accumulation of fluorescent chromolipids was most prominent in the brain, where 99 and 138% increases over the control were detected after 36 and 48 h hyperoxia, respectively. Fluorescent chromolipids appeared in urine already before their concentrations were elevated in tissues. The activity of superoxide dismutase in the brain was initially decreased, followed then by a slight induction of activity at the later time-points. Pulmonary and hepatic catalase activities were markedly decreased after prolonged (36 and 48 h) hyperoxia. In conclusion, fluorescent chromolipid formation seems to be a sensitive indicator of hyperoxia induced oxidative damage in rat tissues. The lipid peroxidation-derived fluorescent chromolipids are eliminated from the body via urinary excretion. Moreover, impaired detoxication of reactive oxygen may be implicated in tissue damage due to hyperoxia. PMID- 1636445 TI - Differential responses in post- and pre-ganglionic adrenal sympathetic nerve activity and renal sympathetic nerve activity after injection of 2-deoxy-D glucose and insulin in rats. AB - The aim of the study was to compare pre-ganglionic adrenal nerve activity (pre aSNA) to post-ganglionic adrenal nerve activity (post-aSNA) in rats after administration of 2-deoxy-D-glucose (2-DG, 500 mg kg-1, i.v.), which mimicks a central hypoglycaemia or to the response in pre-aSNA and post-aSNA to hypoglycaemia after injection of insulin (5U). Renal postganglionic sympathetic nerve recordings (rSNA) in a separate group was used as a reference. Adrenal or renal multifibre nerve activity was recorded in chloralose-anaesthetized Wistar rats. Trimethaphan, a short-lasting ganglionic blocker, was administered i.v. (10 mg kg-1) in order to test for pre- or post-aSNA in the adrenal nerves. The adrenal nerves was considered to contain predominantly post or preganglionic fibres, respectively if the nerve activity in the adrenal nerve decreased (post aSNA) or increased (pre-aSNA). In contrast, all renal nerves showed almost a pure postganglionic activity. Post-aSNA responded with a tendency to increase after the 2-DG injection. The highest value (percentage change from control) 5 min after injection was 12 +/- 9%. The pre-aSNA increased with values of 99 +/- 52% at 3 min and 86 +/- 31% at 5 min (percentage change from control). The activity in the rSNA was only slightly decreased after the injection of 2-DG when compared to pre-drug control activity. There was a significant difference between the pre aSNA vs. post-aSNA at 1 min (P less than 0.05), 3 min (P less than 0.01) and 5 min (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636446 TI - Increased resistance to haemorrhage induced by intracerebroventricular infusion of hypertonic NaCl in conscious sheep. AB - The effect of elevated cerebrospinal fluid Na+ concentration (CSF [Na+]) on the tolerance of blood loss, and concomitant cardiovascular and humoral responses were studied in conscious sheep. A slow (0.7 ml kg-1 min-1) venous haemorrhage was continued until the mean systemic arterial pressure suddenly decreased to less than 50 mmHg, or in the absence of hypotension, until a total blood loss of 25 ml kg-1. Significantly more blood had to be removed to induce hypotension in animals receiving an intracerebroventricular (i.c.v.) infusion (0.02 ml min-1) of 0.5 M NaCl (starting 30 min before haemorrhage and continued throughout the experiment) compared to control haemorrhages without concomitant i.c.v. infusion (22.7 +/- 1.2 ml vs 16.9 +/- 0.9 ml kg-1). In one animal, subjected to 0.5 M NaCl infusion, the blood pressure was still maintained at 25 ml kg-1 of haemorrhage. In spite of a larger blood loss, animals receiving i.c.v. infusion of hypertonic NaCl had an improved recovery of the blood pressure after haemorrhage, due to a better maintained cardiac output rather than to a reinforced increase of the vascular resistance. The improved cardiovascular responses to haemorrhage during elevated CSF [Na+] are not readily explained by the effects on the plasma concentrations of vasopressin, angiotensin II or noradrenaline, although the latter was augmented. The plasma protein concentration decreased already during the 30 min of hypertonic NaCl infusion preceding haemorrhage, and the haemodilution caused by the subsequent blood removal was aggravated, which indicates that this treatment also causes transfer of fluid to the plasma compartment. We conclude that elevated CSF [Na+] increases tolerance to haemorrhage and improves cardiovascular function after blood loss in sheep. Since the haemodynamic responses in many respects were similar to those reported in response to the systemic administration of a small volume of hypertonic NaCl solution in haemorrhagic shock, part of the effect of that treatment may be mediated via cerebral effects of increased Na+ concentration. PMID- 1636447 TI - Atropinization decreases oxytocin secretion in dairy cows. PMID- 1636448 TI - Low birth weight is associated with elevated adult blood pressure in the chronically catheterized guinea-pig. PMID- 1636449 TI - Calciuresis elicited by spontaneous rehydration in dehydrated sheep. PMID- 1636450 TI - [Controversies in the diagnosis and treatment of cancer of the prostate. Meeting of the Uro-oncologic Group of the Spanish Association of Urology. Vigo]. PMID- 1636451 TI - [Vascular complications in 237 recipients of renal transplant from cadaver]. AB - Between July 1976 and June 1990, 244 transplantations were performed. Of the 237 patients monitored, 13 (5.4%) had vascular complications: 10 (77%) renal artery stenosis, 1 (7.7%) primitive iliac artery stenosis, 1(7.7%) renal artery thrombosis, 1 (7.7%) renal vein thrombosis. Six patients underwent surgery (Angioplasty was performed in three patients, re-anastomosis to the common iliac artery in one, by-pass of saphenous vein in another one, while in the last one it was tried a release of the vascular pediculus). Management with drugs was possible in one case. At present, 11 of the 13 patients are still alive and three of the grafts remain functional after a mean follow-up time of 83 months. According to a univariate study, the influential factors in the development of vascular complications are, the identity of Locus A, the type of extraction in Locus B, the length of cold ischaemia, the type of vascular anastomosis and the number of previous rejections. The factors with maximal influence in the development of complications are the type of vascular suture (with or without patch) and the number of previous rejections (according to a study of log regression models). The study demonstrates the significant influence vascular complications have on the graft's durability (p = 0.005). PMID- 1636452 TI - [Renal fungal infection: presentation forms and therapeutic advances]. AB - Fluconazole is a broad spectrum anti-fungal agent which combines good tolerance, efficacy and low toxicity, and offers useful advantages in the treatment of certain forms of mycosis. Three cases of renal fungal disease treated with surgery (nephrectomy in two cases and pyelolitectomy plus partial nephrectomy in the third one) and fluconazole or amphotericin B are presented. In all three cases there was at least one predisposing factor (diabetes, urolithiasis, urinary catheter, previous therapy with antibiotics, or AIDS), and the causing pathogens were Candida and Mucor. Administration of fluconazole 100 mg b.i.d. for 4 weeks in the two candida infected patients accomplished a complete cure of the disease. Incidence, etiopathology, presentation forms and diagnostic techniques of urinary mycosis are analyzed together with the current therapeutical options, making special reference to fluconazole. PMID- 1636453 TI - [Abdominal echography to determine the weight of the prostate]. AB - The relationship of post-operatively determined prostatic gland weight and that calculated prior the procedure, by means of abdominal ultrasound techniques using the "ellipsoid method", has been studied in 88 patients undergoing retropubic adenectomy. The regression line was nearly optimal, Y = 0.946 X + 2.295, and the correlation coefficient between both weight measures was r = 0.915. Abdominal ultrasound examinations are a simple, quick and safe means to evaluate prostate weight, prior to deciding the type of surgery (open adenectomy or transurethral resection) for prostate adenoma. PMID- 1636454 TI - [Complete androgenic blockade: myth or reality. Study and follow-up of 35 patients with advanced carcinoma of the prostate]. AB - Retrospective evaluation of the efficacy of complete androgenic blockade started by Labrie et al. using therapy with leuprolide acetate in monthly dosage of 7.5 mg i.m. associated to flutamide at the usual dosage in 35 patients with prostate adenocarcinoma in C-D1-D2 stages, who had not been given prior anti-neoplastic therapy. Clinical and analytical control studies were carried out during therapy follow-up for a maximum time of 36 months. The objective response of adverse events that can be superimposed to previous studies carried out with analogs on daily administration was assessed. Castration levels achieved were maintained for the length of the study below 50 ng/dl. Correlation between tissue type, rated according to the Mostofi classification, evolution or degree of response obtained and preserved increase of tumour markers (PSA, PAP, LDH, Prolactin) was evaluated; the evolution observed in patients who maintained high values of markers was worse with the referred treatment. PMID- 1636455 TI - [Incidence and characteristics of multiple neoplasms in urologic patients]. AB - The incidence and features of malignant primary multiple (MPM) neoplasias found in clinical urological patients have been analyzed so as to determine the actual magnitude of the problem and to obtain a better knowledge of this disease. For this reason, case histories of patients with MPMN, where at least one of the involved neoplasia was urological, were retrospectively studied. The study included a 9-year follow-up period and followed the Warren and Gates inclusion criteria. The number of MPMN patients was 23, representing an incidence of 6.1% among patients with urological neoplasias. Mean age at the time of discovery of the second tumour was 77.1 years. In the 15 patients with metachronic tumours, the time interval between the first and second tumours ranged between 1 to 25 years (average 5.4 years). The most frequently observed tumour association was bladder transitional carcinoma and prostate adenocarcinoma. The cause of death was always the second neoplasia. PMID- 1636456 TI - [Prognostic value of local vascular infiltration in infiltrating transitional carcinoma of the bladder]. AB - The present retrospective study analyzes the evolution and survival of 79 patients with bladder infiltrant transitional carcinoma (T2-T3), which were treated with radical cystectomy and bilateral ilio-obturating lymphadenectomy. Pre-operative radiotherapy (57/79) and neo-adjuvant chemotherapy (24/79) was used as supplementary therapy. The univariate analysis showed the relationship between tumour vascular infiltration (TVI) and presence of nodes micrometastasis (p = 0.002). The variables with greater forecast power in the multivariate analysis for survival were a decline in the post-radio and/or neo-adjuvant chemotherapy tumoral stage (p = 0.000) and TVI (p = 0.001). Survival decreased significantly in patients with TVI (p = 0.008), this finding denoting a worse prognosis than the presence of nodular micrometastasis (p = 0.01). PMID- 1636457 TI - [Triple ureter in crossed renal ectopy: an embryologic rarity]. AB - Presentation of one case of CRE (crossed renale ectopia) with triplicity (trifidity) of the ortho and ectopic collector systems, due to the existence in both cases of pyelourethral bifidity and a third cranial blind ureter. This case represents a casual finding during a routine study of a female patient with orthostatic and exertion urinary incontinence (EUI). The case idiosyncrasies, which initially elicited the possibility of urethral ectopia, are analyzed. Incidence and variants of this unusual congenital anomaly are commented upon. PMID- 1636458 TI - [Solitary adrenal gland hydatid cyst]. AB - Presentation of one case of solitary suprarenal hydatid cyst. Clinical diagnosis was made from a right lumbar pain, achieving identification of the parasitic disease by radiological and biological means. Treatment combined mebendazole and surgery. Both therapeutical options are discussed. PMID- 1636459 TI - [Distal tubular renal acidosis with nephrocalcinosis]. AB - Nephrocalcinosis and distal tubular acidosis are two infrequent processes caused by several etiologies which can present in association. This paper describes a clinical case of tubular acidosis and explains the differential diagnosis of both entities. PMID- 1636460 TI - [Spontaneous renocolic fistula secondary to pyonephrosis of lithiasic etiology]. AB - Description of one case of spontaneous fistulization between a renal calix and a descending colon, secondary to lithiasic pyonephrosis. Diagnosis was carried out by means of ascending pyelography without it being clinically suspected. Treatment is surgical, combining nephrectomy, fistula resection and closure of the colic gap. Etiology, favouring factors, diagnosis and treatment are explained. PMID- 1636461 TI - [Paratesticular rhabdomyosarcoma]. AB - Presentation of one case of embryonic paratesticular rhabdomyosarcoma in a 19 year old male. Following high inguinal radical orchiectomy, he required hemiscrotectomy, and it was found to be a foreign body granuloma. Prior to staging lymphadenectomy, therapy was complemented with radiotherapy and polychemotherapy according to a VAC protocol. The patient shows clinical remission at two and a half years after being diagnosed and one and a half years after completion of treatment. PMID- 1636462 TI - [Bacteremia caused by Clostridium perfringens as a complication of ureterosigmoidostomy]. AB - A 63 year old male underwent cystectomy and ureterosigmoidostomy after diffuse carcinoma "in situ" of the bladder was discovered, and thereafter, various episodes of pyelonephritis and metabolic imbalance, in one of them, a left pneumo ureter and a positive blood culture for Clostridium Perfringens and enterococci was detected. Empiric therapy with Aztreonam was started, and changed after to high-dose intravenous amoxicillin. Two months later the ureterosigmoidostomy was converted to an ileal conduit. The patient has remained asymptomatic on subsequent controls. PMID- 1636463 TI - [Inverted papilloma of the renal pelvis: presentation of a case]. AB - Contribution of a new case of urothelial inverted papilloma of rare location. Its invariably benign character and resolution with conservative surgery, forces to bear in mind this possibility when encountering pelvic repletion defects which can be mistaken, even after exfoliative cytologies, for low-degree transitional carcinomas, there being necessary to exhaust all procedures within our grasp in order to establish a diagnosis prior to definite surgery. PMID- 1636464 TI - [Double renal tumor: histogenetic implications]. AB - Presentation of a new case of synchronic concurrence of renal adenocarcinoma and papillar carcinoma of renal pelvis on the same kidney. The origin of this double malignant renal tumour remains unknown, although several hypothesis have been raised. We believe that coexistence of both tumours is more than casual and we would underscore the morphogenetic interpretation of such coincidence. PMID- 1636465 TI - [Renal hemangiomas: a clinical case and review of the literature]. AB - Renal haemangiomas, an unusual cause of renal haematuria, are benign vascular dysplasias of uncertain etiology. Usually asymptomatic, their clinical manifestation is a unilateral renal haematuria associated or not to obstructive urological disease through accumulation of clots in the urinary tract and arterial hypertension when associated to a major arteriovenous shunt. Arteriographic diagnosis is based on the size of the vascular malformation but the absence of findings in the arteriography does not eliminate the presence of small-sized haemangiomas or microhaemangiomas responsible for the renal chronic haematuria, also labelled as "essential haematuria", which sometimes can be diagnosed through endoscopic examination of the renal cavities. This report presents one case of renal haemangioma which appeared as a massive, sudden haematuria and prompted haemodynamic instability requiring haemotherapy. Following arteriographic diagnosis, selective transarterial embolization was undertaken with three modified Gianturco's metal helicoids, to which the patient responded favourably. The report includes a review of the clinical, pathological, diagnostic and therapeutical features of renal haemangiomas. PMID- 1636466 TI - Personal and parental problem drinking: effects on problem-solving performance and self-appraisal. AB - This study examined the problem-solving performances and self-appraisals of problem-solving ability of college-age subjects with and without parental history of problem drinking. Contrary to our predictions, children of problem drinkers (COPDs) were rated as somewhat more effective in their problem-solving skills than non-COPDs, undermining prevailing assumptions about offspring from alcoholic households. While this difference was not large and was qualified by other variables, subjects' own alcohol abuse did exert a detrimental effect on problem solving performance, regardless of parental history of problem drinking. However, a different pattern was evident for problem-solving self-appraisals. Alcohol abusing non-COPDs saw themselves as effective problem-solvers while alcohol abusing COPDs appraised themselves as poor problem-solvers. In addition, the self appraisals of alcohol-abusing COPDs were consistent with objective ratings of solution effectiveness (i.e., they were both negative) while alcohol-abusing non COPDs were overly positive in their appraisals, opposing the judgments of trained raters. This finding suggests that the relationship between personal alcohol abuse and self-appraised problem-solving abilities may differ as a function of parental history of problem drinking. Limitations on the generalizability of findings are addressed. PMID- 1636467 TI - Compliance to nicotine gum recommendations in a multicomponent group smoking cessation program: an exploratory study. AB - This is an exploratory study of compliance to nicotine chewing gum in a multicomponent group smoking cessation program where usage was optional. Two thirds (24 out of 36) of the participants across three group sessions complied with the recommendation to use nicotine chewing gum. All subjects received standard instructions. Demographic characteristics (age, sex, site of employment) and smoking variables (number of years smoked, pretreatment number of cigarettes smoked per day, and nicotine dependence) failed to predict compliance, but complaint participants reported significantly greater confidence at their ability to not smoke in various challenging situations as measured by the Smoking Self Efficacy Questionnaire. Those who did comply mostly failed to chew the gum in the way instructed. Reduced craving was cited as the most positive feature of gum use. PMID- 1636468 TI - Reactivity to alcohol-relevant beverage and imaginal cues in alcoholics. AB - This study was designed to explore three primary facets of reactivity to alcohol relevant stimuli among alcoholics: (a) comparison of exposure to an alcohol containing beverage vs. an appropriate, standardized control beverage; (b) efficacy of imaginally presented cues to elicit reactivity, alone and in combination with beverage cues; and (c) examination of the recovery process. Forty-eight male veterans attending an inpatient alcohol treatment program served as participants and were randomly assigned to one of four groups in a 2 (Alcohol vs. Lemonade Beverage) X 2 (High-Risk vs. Low-Risk Imagery) design. Heart rate reactivity to Beverage cues was consistent with previous research. An interaction of Beverage and Imagery manipulations during recovery revealed both experimental manipulations influenced heart rate, although the Alcohol/High-Risk Imagery exposure group did not demonstrate enhanced effects. Both manipulations also had an impact on ratings of desire to consume alcohol. These findings provide further support for the reliability of cue reactivity effects, and suggest the utility of imaginal exposure procedures as a component of a comprehensive cue reactivity assessment. PMID- 1636469 TI - Do weight concerns hinder smoking cessation efforts? AB - This study examined the hypothesis that weight concerns interfere with smoking cessation efforts. Four hundred fifty-nine women screened for participation in a smoking cessation treatment program completed Stunkard's Three Factor Eating Questionnaire (1981), measures of smoking-specific weight gain concern, and smoking history measures. Success in current cessation efforts was assessed 6 months following treatment. The restraint subscale of the TFEQ was associated with lower baseline level of nicotine dependence, a history of smoking fewer cigarettes, and longer prior periods of successful smoking abstinence. Baseline level of nicotine dependence and treatment group were significant predictors of smoking cessation at 6 months posttreatment. Restraint score was marginally predictive of higher rates of abstinence from smoking at 6 months when baseline level of nicotine dependence and treatment group were controlled. These results do not support the hypothesis that weight concerns interfere with smoking cessation attempts. PMID- 1636470 TI - Incarcerated adolescents' attributions for drug and alcohol use. AB - Incarcerated adolescents' attributions for drug use were investigated. A new 50 item questionnaire, the Inventory of Drug Taking Situations (IDTS), was used to assess reasons for use. The IDTS yields eight subscales corresponding to risky situations identified by Marlatt and others. On the IDTS, subjects indicate how frequently they used their drug of choice when confronted with each risky situation. The IDTS scales had good internal consistency and higher scores were significantly associated with self-reports of drug use frequency. Furthermore, IDTS scores were most valid for the type of drug the measure was filled out about. Adolescents reported that they tended to use more frequently in response to positive and/or interpersonal experiences, as opposed to negative and/or internal ones. Positive, negative, interpersonal, and internal reasons for use were all equally correlated with frequency of use. In the most heavily drug involved adolescents, however, negative reasons were more highly correlated with frequency of use than positive reasons. Treatment implications are discussed. PMID- 1636471 TI - Relationship between two ways of measuring alcohol dependence. AB - One of the main difficulties hampering research with the concept of the alcohol dependence syndrome is the lack of a set of agreed-upon operational definitions of each element composing the syndrome. To illustrate the possible impact of these different operationalizations of alcohol dependence on research results, this article shows the correlation between two different sets of items used to operationalize DSM-III-R alcohol dependence in a clinical sample. Results show that the correlations between the various sets of items are low. About 60% of the correlations are in between .21 and .40. These results suggest that different operationalizations of dependence may not be measuring the same phenomena, and should not be seen as interchangeable. PMID- 1636472 TI - Treatment response in obese binge eaters: preliminary results using a very low calorie diet (VLCD) and behavior therapy. AB - The present study compared the treatment response of male and female obese binge eaters and nonbinge eaters attending a university-based weight reduction program employing a very low calorie diet (VLCD) and concurrent behavior therapy. Twenty nine percent of female patients (n = 19) and 22% of male patients (n = 6) were characterized as binge eaters based on their scores on the Binge Eating Scale. No significant differences were found between binge and nonbinge groups on measures of weight loss, adherence to the diet, or drop-out rate, although a trend towards greater attrition in the binge group (32%) relative to the nonbinge group (17%) was noted. However, binge eaters had significantly higher pretreatment levels of trait anxiety, state anxiety, and depression as well as higher within treatment levels of anxiety and depression despite significant reductions in depression over the course of treatment. Further examination revealed a binge status X sex interaction effect on state anxiety. Binge-eating females had significantly higher anxiety levels pretreatment and throughout the 10 weeks of the study. No differences between binge and nonbinge males on levels of anxiety were found. These preliminary results tentatively suggest that a VLCD in conjunction with behavior therapy may be an effective method of weight loss for this segment of the obese population, but that elevated levels of anxiety persist in female patients. Future studies must address the long-term maintenance of weight loss in this population as well as other treatment strategies. PMID- 1636473 TI - Smoking as a weight-control strategy and its relationship to smoking status. AB - This investigation assessed the use of cigarettes for weight control and the relative impact of weight-control smoking and dietary restraint on current smoking status and future intent to quit smoking in 221 smokers and ex-smokers. We found that weight-control smokers were more likely to gain weight in previous quit attempts, had less formal education, scored higher on dietary restraint, and reported higher weight among biologic parents. Females who gained weight in previous cessation attempts were also more likely to be weight-control smokers. Current smoking was predicted by decreasing age, weight-control issues, lower dietary restraint, less education, more cigarettes smoked per day, less obesity in parents, and more cessation attempts. Females with higher relative weights were more likely to be smokers than males with less relative weight. The results indicated that the number of fewer prior quit attempts, higher levels of weight control smoking, and increasing age predicted plans not to quit smoking. These results have important implications for those subjects at risk for continued smoking. PMID- 1636474 TI - Restraint, food choice, and cognitions. AB - Restrained eaters were hypothesized to prefer high kilocalorie (KCAL) food when given a choice of both high and low KCAL foods after consuming a high KCAL preload. Study 1 found no differences between restrained and unrestrained eaters in food choice in either preload condition. Study 2 found that preloaded subjects preferred lower KCAL foods than subjects in the no preload condition. Both restrained and unrestrained eaters ate less food after consuming a high KCAL preload than after no preload. Preloaded restrained eaters expressed a greater number of control-related thoughts regarding food than any other group; however, these thoughts did not mediate disinhibited eating. Implications for restraint theory are discussed. PMID- 1636475 TI - Validity of the Mizes Anorectic Cognitions scale: a comparison between anorectics, bulimics, and psychiatric controls. AB - The Mizes Anorectic Cognition scale (MAC) was developed to assess cognitions relevant to anorexia and bulimia nervosa. It assesses three areas: rigid weight regulation, weight and approval, and excessive self-control as a component of self-esteem. Previous research has supported the validity and reliability of the scale. The purpose of the present study was to extend previous work to include anorectic patients, examine the specificity of the scale by making comparisons to a psychiatric (rather than normal) control group, and secondarily, to conduct a preliminary comparison of bulimics and anorectics. Results showed that for the total MAC score and the subscales, bulimics and anorectics scored higher than psychiatric controls, though they did not differ from each other. PMID- 1636476 TI - Stability of salivary cotinine sent through the U.S. mail for verification of smoking status. AB - Until now mass media smoking cessation studies have relied almost exclusively on self-reports of smoking cessation because biochemical confirmation has not seemed practical. This study investigated the reliability of mailed salivary cotinine specimens for the determination of smoking status. Two simultaneous saliva specimens were obtained from 10 smokers and 10 nonsmokers. One of each pair was frozen immediately. The other was sent through the local U.S. mail and then subjected to additional physical agitation and heat before being frozen. All specimens were subsequently analyzed for cotinine. No cotinine was detectable in any of the nonsmokers' specimens. There was excellent correlation between the paired smokers' specimens. These results show that the mailing of saliva specimens for cotinine analysis is practical and provides accurate data on smoking status. It is an approach which could easily be used in mass media smoking cessation studies to biochemically confirm smoking behavior. PMID- 1636477 TI - Artificial neural networks in bioprocess state estimation. AB - The application of artificial neural networks to the estimation and prediction of bioprocess variables is presented in this paper. A neural network methodology is discussed, which uses environmental and physiological information available from on-line sensors, to estimate concentration of species in the bioreactor. Two case studies are presented, both based on the ethanol production by Zymomonas mobilis. An efficient optimization algorithm which reduces the number of iterations required for convergence is proposed. Results are presented for different training sets and different training methodologies. It is shown that the neural network estimator provides good on-line bioprocess state estimations. PMID- 1636478 TI - A human genome analysis system (HUGA-I) developed in Japan. AB - A part of the Japanese human genome project has resulted in the development of a world original human genome analysis system. Circumstances of the project, objective, design concept, and constitution of the system are described in the paper. PMID- 1636479 TI - Use and engineering aspects of immobilized cells in biotechnology. AB - A short review of the research in the past two years (1990-1991) on immobilized whole cells, such as microbial, plant, and animal cells, is presented including a discussion from an engineering point of view. Recent works concerning the intraparticle mass transfer effect on immobilized microbial cells by the authors and their co-workers are also introduced. Finally, future prospects of the immobilized cell system will be discussed. PMID- 1636480 TI - Modelling the growth of filamentous fungi. AB - Despite the considerable industrial importance of filamentous fungi there have been very few attempts to model the complex growth process of these microorganisms. With a new generation of high performance, computerized bioreactors and new analytical techniques it is possible to obtain the necessary experimental data for setting up reliable structured models describing the growth process of filamentous fungi. It is therefore interesting to review the mathematical models described previously in the literature and the experimental data on which these models are built. Only structured models are considered due to the complex metabolism of filamentous fungi and to the natural cellular structuring of the biomass, i.e. the biomass can be divided into different cell types. In order to set up good structured models it is strictly necessary to have a detailed knowledge of the mechanisms underlying the growth process. This involves both biochemical insight and understanding of the interactions between different macromolecules and cytological organelles. PMID- 1636481 TI - An overview of the biotechnology research activities in the European Community. AB - The research in Biotechnology is an important element for the competitive environment of European bioindustrial activities. In this article the evolution of the Biotechnology programmes in the European Community is presented. PMID- 1636483 TI - Immunochemically based assays for process control. AB - Immunoanalysis for process control is reviewed. The development of non equilibrium immunoassays from a manually operated flow injection system to a completely computerized system for sample analysis as well as calibration and data evaluation is discussed. Several other approaches in using immunochemistry in biosensors for process control are discussed. The fact that reuse of antibodies raises specific demands on their properties is discussed. Even if the area is young, much progress has been achieved and one can foresee an interesting future development of the area. PMID- 1636482 TI - Use of regulated secretion in protein production from animal cells: an overview. AB - Traditional industrial cell culture processes require extensive downstream product refining due to low product titer and purity in the spent growth medium. A controlled secretion process incorporating cells derived from endocrine or exocrine organs could potentially alleviate this processing burden by dynamically decoupling product recovery from cell growth and product biosynthesis. In addition, such specialized secretory cells may be uniquely capable of performing desirable post-translational processing of the secretory product. We briefly review the biology of regulated protein secretion as well as the biology and biochemistry of the signal transduction mechanisms by which regulated systems respond to environmental stimuli. Drawing on these and other basic principles from cell biology and bioengineering, we describe the important features of a controlled secretion process. Among other issues we discuss the choice of cell lines, expression systems, cell culture methods, and bioreactor configurations. We extensively analyze the kinetics of regulated secretion in the context of a controlled secretion process. This discussion is illustrated with experimental results from two model cell lines, recombinant AtT-20 and beta TC3, expressing recombinant human endocrine hormones or native murine insulin respectively. PMID- 1636484 TI - The induction of cellular group II phospholipase A2 by cytokines and its prevention by dexamethasone. AB - Treatment of rat glomerular mesangial cells with interleukin-1 beta, tumor necrosis factor or forskolin resulted in the secretion of phospholipase A2 activity into the culture medium. Essentially all of this secreted phospholipase A2 activity was recognized by monoclonal antibodies elicited against rat liver mitochondrial 14 kDa group II phospholipase A2. Immunoblot analysis and gel filtration confirmed the presence of only 14 kDa phospholipase A2 in the culture supernatant. This enzyme could hardly be detected in unstimulated mesangial cells and after a lag period of 6 to 8 hours becomes detectable in both cells and culture medium. The results indicate that the increased phospholipase A2 activity upon treatment of the cells with cytokines is not due to activation of an existing cellular pool of enzyme but is caused by induced synthesis of group II phospholipase A2. Pretreatment of the cells with dexamethasone, a known inhibitor of prostaglandin synthesis, dose-dependently inhibits cytokine-induced phospholipase A2 activity. Western immunoblot analysis of cells and culture medium demonstrates that this is not due to inhibition of existing phospholipase A2 but because dexamethasone prevents the cytokine-induced synthesis of phospholipase A2 protein. PMID- 1636485 TI - Brain phospholipases and their role in signal transduction. PMID- 1636486 TI - Modulation of arachidonic acid metabolism in cultured rat astroglial cells by long-chain N-3 fatty acids. PMID- 1636487 TI - Aplysia californica contains a novel 12-lipoxygenase which generates biologically active products from arachidonic acid. AB - Physiologic stimulation of identified neurons in ganglia of the marine mollusk, Aplysia californica, leads to the generation of arachidonic acid metabolites. Using various preparations of Aplysia nervous tissue, we have identified 12 lipoxygenase products including the inactive 12-hydroxyeicosatetraenoic acid (12 HETE) and the biologically active 12-ketoeicosatetraenoic acid (12-KETE) and 8 hydroxy-11(12)-epoxyeicosatrienoic acid (8-HEpETE). Each of these metabolites can be derived from the intermediate 12-hydroperoxyeicosatetraenoic acid (12-HPETE), which can itself activate several identified neurons in Aplysia. In spite of conflicting results in studies of mammalian brain 12-lipoxygenase, Aplysia nervous tissue clearly contains an enzymatic activity which generates stereochemically pure 12(S)-HETE. This activity is destroyed by boiling and is sensitive to nonspecific lipoxygenase inhibitors but not to agents specific for other lipoxygenases or the cyclooxygenase enzyme. The Aplysia 12-lipoxygenase is highly enriched in neural tissue and is almost completely absent in the neural sheath, which is composed primarily of connective tissue and muscle. Preliminary purification has shown that, in contrast to the previously characterized 12 lipoxygenases, the Aplysia enzyme is associated with membrane fractions and is not found in the cytosol. Further studies are in progress to determine the kinetic properties and to define the cellular and subcellular distribution of this novel lipoxygenase. PMID- 1636489 TI - Phospholipid metabolism and second messenger system after brain ischemia. AB - To evaluate possible involvement of phospholipid metabolism and related second messenger systems in the selective neuronal damage after ischemia, we measured changes of polyphosphoinositides (PPIs) and free fatty acids (FFAs) in a model of 5-min or 10-min ischemia and reperfusion in gerbils. The binding activity of 3H phorbol 12,13-dibutyrate (PDBu) for protein kinase C (PKC) and 3H-inositol 1,4,5 triphosphate (IP3) for IP3 receptors was demonstrated autoradiographically. Induction of 70 KDa heat shock protein (HSP70) mRNA and amyloid precursor protein (APP) mRNA was also examined using Northern blot analysis. In the parietal cortex (an area resistant to transient ischemia), PPIs decreased during ischemia and recovered rapidly after reperfusion. However, recovery did not occur in the hippocampal CA1 area (an area more vulnerable to transient ischemia). In the cortex, arachidonic acid (AA) increased during ischemia and returned to baseline by 7 days after reperfusion; in the CA1 area, the AA level remained elevated even after 7 days of reperfusion. PDBu binding decreased in CA1 cells after 2 days of reperfusion. IP3 binding began to decrease at 5 hr of reperfusion, which is far earlier than either the onset of decreased PDBu binding or the observation of neuronal damage by light microscopy. The induction of HSP70 mRNA occurred, but the induction of APP mRNA did not. Regional differences in the induction of HSP70 mRNA were found; CA1 cells produced less HSP70 mRNA than cortical cells 8 hr after transient ischemia. These results suggest that CA1 cell membranes may not recover after transient ischemic attack, and that the membranes of the endoplasmic reticulum, which have IP3 receptors, may undergo alterations earlier than cytoplasmic membranes. The variable induction of HSP70 mRNA may be related to regional differences in vulnerability in cortical and hippocampal CA1 cells after transient ischemia. Involvement of excitatory neurotransmission in the induction of HSP70 has been suggested. The combined data may support a role for inositol phospholipid metabolism, changes in related second messenger systems, and induction of HSP70 in the excitotoxic mechanism of hippocampal CA1 neuronal damage, death, and repair. PMID- 1636488 TI - Essential fatty acid deficiency in cultured SK-N-SH human neuroblastoma cells. AB - SK-N-SH neuroblastoma cells grown under standard culture conditions contain significant amounts of Mead acid (20:3 omega 9) in phospholipids, indicating essential fatty acid (EFA) deficiency. The amount of esterified 20:3 omega 9 was augmented by growth in a chemically defined EFA-free medium, whereas its presence could be virtually eliminated by supplementation of the culture medium with either arachidonic (20:4 omega 6; AA), eicosapentaenoic (20:5 omega 3; EPA), or linolenic (18:3 omega 3) acids. Substitution of Mead acid for omega 6 fatty acids, particularly evident in phosphatidylinositol (PI), indicates a compensatory replacement of omega 9 for omega 6 fatty acids during EFA deficiency. Studies evaluating [3H]scopolamine binding to the M3 muscarinic acetylcholine receptors (mAChRs) present in these neurotumor cells as well as effects of carbachol on phosphoinositide turnover and intracellular Ca2+ mobilization, indicate that the biosubstitution of 20:4 omega 6 with 20:3 omega 9 does not detectably impair these measures of signal transduction. Stimulation of mAChRs with carbachol increased the cellular mass of diacylglycerol (DAG) approximately 60%. On the basis of distinctive fatty acid "signatures" of each of the phospholipid classes, it is concluded that the DAG initially released following muscarinic stimulation is derived from phosphoinositide breakdown. After several minutes, however, a significant amount of DAG comes from phosphatidylcholine (PC) as well. In contrast to DAG, the composition of phosphatidate (PA) following receptor stimulation closely resembles that of the phosphoinositides, even at the later time points examined. These results support a selective phosphorylation of DAG arising from the stimulated breakdown of phosphoinositides, favoring the conservation of the 1-stearoyl, 2-arachidonoyl (or 20:3 omega 9) moiety. PMID- 1636490 TI - Impact of dietary fatty acid balance on membrane structure and function of neuronal tissues. AB - Neural tissue has generally been viewed as resistant to structural changes induced by exogenous factors. Research has shown that the brain responds to changes in diet by altering neurotransmitter synthesis, and by shifting neuroendocrine controls over a variety of physiological events. Animal model research also indicates that fatty acid constituents and synthesis of brain structural lipid in membranes undergoing turnover can be altered by changing the composition of dietary fat. In growing animals, the balance between dietary omega 6 and omega 3 fatty acids influences brain phospholipid fatty acid composition, phosphatidylethanolamine methyltransferase activity, and rate of phosphatidylcholine biosynthesis via the CDP-choline pathway. It is concluded that biosynthetic control mechanisms regulating synthesis of brain structural lipid, in particular phosphatidylcholine, respond to exogenous factors and represent a normal physiological response by the brain. This response may provide a mechanism for therapeutic treatment of disorders involving degeneration of brain structural lipid. PMID- 1636491 TI - Structural and functional importance of dietary polyunsaturated fatty acids in the nervous system. AB - The nervous system is the organ with the second greatest concentration of lipids. These lipids participate directly in membrane functioning. Brain development is genetically programmed. It is therefore necessary to ensure that nerve cells receive an adequate supply of nutrients, especially of lipids, during their differentiation and multiplication, and throughout their lives. The effects of polyunsaturated fatty acid deficiency have been extensively studied; prolonged deficiency leads to death in animals. Linoleic acid is now universally recognized to be an essential nutrient. Until recently, however, alpha-linolenic acid was considered non-essential. Feeding animals with oils that have a low alpha linolenic content results in all brain cells and organelles and various organs having reduced amounts of 22:6n-3, which is compensated for by an increase in 22:5n-6. The speed of recuperation from these anomalies is extremely slow for brain cells, organelles, and microvessels, in contrast to other organs. A decrease in alpha-linolenic series acids in the membranes results in a 40% reduction in the Na(+)-K(+)-ATPase of nerve terminals and a 20% reduction in 5' nucleotidase. Some other enzymatic activities are not affected, although membrane fluidity is altered. A diet low in alpha-linolenic acid induces alterations in the electroretinogram which disappear with age; motor function and activity are little affected, but learning behavior is markedly altered. The presence of alpha linolenic acid in the diet confers a greater resistance to certain neurotoxic agents (triethyl-lead). During the period of cerebral development, there is a linear relationship between brain content of n-3 acids and the n-3 content of the diet up to the point where alpha-linolenic levels reach 200 mg for 100 g of food intake. Beyond that level there is a plateau. For other organs, such as the liver, the relationship is also linear up to 200 mg/100 g, but then there is merely an abrupt change in slope and not a plateau. When dietary 18:2n-6 content was varied, it was noted that 20:4n-6 optimum values were obtained at 150 mg/100 g for all nerve structures, 300 mg for testicle and muscle, 800 mg for kidney, and 1200 mg for liver, lung and heart. A deficiency in alpha-linolenic acid and an excess of linoleic acid have the same main effect: an increase in 22:5n-6 levels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1636492 TI - Long and very long polyunsaturated fatty acids of retina and spermatozoa: the whole complement of polyenoic fatty acid series. PMID- 1636493 TI - Phospholipid metabolism in rat intestinal mucosa after oral administration of lysophospholipids. AB - The present results indicate that PS, a phospholipid contained in small amounts in the human diet and not included in plasma lipoproteins, may be used to influence phospholipid metabolism in intestinal mucosal cells. Since PS influx into absorptive cells occurs after its hydrolysis to lysoPS, this metabolite may be used to increase the absorption of this phospholipid. These data show that lysoPS, after diffusion into intestinal cells, is sequentially converted into PS and PE (which make up a minor fraction of the lipids present in lipoproteins). As expected, lysoPS given together with radiolabeled unsaturated fatty acids was unable to promote their transfer into plasma lipoproteins. In this respect lysoPS differed from lysoPC, the latter increasing the appearance of dietary fatty acids in plasma. When given together, lysoPS decreased the lysoPC-induced transfer of unsaturated fatty acids into plasma. This effect required addition of triglycerides to the lipid mixture. In attempting to explain this triacylglycerol dependent inhibition by lysoPS, we found that this phospholipid increased the incorporation of glycerol into mucosal cell PC. In contrast, lysoPC was inhibitory. Furthermore, in the presence of labeled inositol, lysoPC (but not lysoPS) promoted the appearance of labeled phosphatidylinositol. The data thus suggest that the two lysophospholipids differ in promoting the two main pathways of PC synthesis in the intestinal cells. While lysoPC favors PC synthesis by reacylation, lysoPS enhances the CDP-choline pathway of PC synthesis. PMID- 1636494 TI - Carbachol-stimulated release of arachidonic acid and eicosanoids from brain cortex synaptoneurosome lipids of adult and aged rats. AB - Synaptoneurosomes from the brain cortex of adult rats (4 months old) and aged rats (27 months old), prelabeled with [14C]arachidonic acid (AA), were used as the source of enzyme(s) and substrates to study the effect of a cholinergic agonist on the release of AA and eicosanoids. In synaptoneurosomes from adult brains, carbachol, the nonhydrolyzable analog of acetylcholine, increased AA release by 16% in the presence of 2 mM calcium. This agonist-mediated AA release occurred specifically from phosphatidylinositol (PI). Concomitantly, carbachol in the presence of 2 mM Ca2+ significantly activated the formation of 15-HETE and PGF2 alpha. This effect of carbachol on the level of eicosanoids was also observed in the presence of endogenous calcium. In synaptoneurosomes from aged brains, carbachol had no effect on the release of AA and eicosanoids. The results of studies involving inhibitors of phospholipase A2 (PLA2) and phospholipase C (PLC) suggested that PLA2 is almost completely responsible for the Ca(2+) dependent, carbachol-mediated AA liberation. The distribution of labeled AA in the lipids after incubation of synaptoneurosomes in the presence of 2 Mm Ca2+ and carbachol indicated that in aged synaptoneurosomes, the muscarinic receptor mediated degradation of phosphoinositides through phospholipase C is preserved, but the turnover of the phosphoinositide cycle is probably suppressed. These results indicate that aging significantly affects the population of cholinergic muscarinic receptors coupled to PLA2. PMID- 1636495 TI - Carbachol-induced stimulation of inositol phosphates, arachidonic acid and prostaglandin F2 alpha in rabbit retina. PMID- 1636496 TI - Induced and spontaneous seizures in man produce increases in regional brain lipid detected by in vivo proton magnetic resonance spectroscopy. AB - Elevations of brain concentrations of arachidonic acid and other free fatty acids (FFAs) by seizures induced in animals were demonstrated some years ago. Similarly, large shifts of potassium (K+) from intra- to extracellular space during seizure activity have been documented in numerous studies. More recent studies of cell membrane function demonstrated a direct effect of FFAs on membrane K+ conductance, suggesting that FFAs may play a primary role in seizure evolution in brain tissue. Using electroconvulsive therapy (ECT), in which generalized seizures are induced in patients by passage of electrical current, as a controlled human model of seizures, we studied the in vivo biochemical effects of single generalized seizures with localized proton magnetic resonance spectroscopy (1H MRS). We found that ECT reliably induces an elevation in the lipid signal that resonates at approximately 1.2 ppm. We observed a similar increase in brain lipids in a patient with temporal lobe epilepsy temporarily off medication; the signal disappeared after re-medication. Similar observations were noted for a subject with focal gliosis bordering a resected brain tumor. Finally, acute alcohol effects seem also to induce observable lipid changes. The 1H MRS technique does not yet permit direct identification of the specific lipids involved but analysis of cerebrospinal fluid obtained by lumbar puncture before and immediately after ECT may permit more precise characterization of the observed lipid increases. Theoretical and clinical implications of these results for the study of brain FFAs and epilepsy will be discussed. PMID- 1636497 TI - Characteristics and possible functions of mast cell phospholipases A2. AB - Phospholipase A2 activity in lysates of mast cells and their related cells [mouse bone marrow-derived IL-3 dependent mast cells (BMMC), rat connective tissue mast cells (CTMC), and rat mastocytoma RBL-2H3 cells] was measured using phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylcholine (PC) as exogenous substrates. Both BMMC and RBL cells showed rather high phospholipase A2 activity, whereas CTMC showed only weak activity. These cells contained at least three types of phospholipase A2. Type 1 enzyme showed no appreciable affinity to heparin, and preferentially hydrolyzed either PC or PE, both of which have an arachidonic acid at the sn-2 position. The activity was absorbed by monoclonal antibody against rabbit platelet cytosolic 85-kDa phospholipase A2. Type 2 enzyme had an affinity to heparin, and was completely inhibited by anti-rat platelet 14-kDa secretory phospholipase A2. This enzyme could be expressed as an "ecto-type" enzyme on the cell surface and might be secreted from cells when mast cells are activated. Type 3 enzyme also had an affinity to heparin, but was separated from type 2 enzyme on reverse-phase HPLC. This enzyme did not interact with anti-14-kDa secretory enzyme antibody. Purified type 3 enzyme (30-kDa) specifically hydrolyzed PS. p-Bromophenacylbromide inhibited all types of phospholipase A2, whereas mepacrine inhibited type 2 and type 3 enzymes, but not type 1 enzyme. Type 2 enzyme was also inhibited by the specific antibody, complement degradation product, and a small-molecular-weight inhibitor. Histamine release was inhibited by all these inhibitors, whereas PGD2 production was inhibited only by p-bromophenacylbromide. Possible roles for these phospholipases A2 in mast cell function are proposed. PMID- 1636498 TI - Network of signal transduction pathways involving lipids: protein kinase C dependent and -independent pathways. PMID- 1636499 TI - Essential fatty acids and neurodevelopmental disorder. PMID- 1636500 TI - Regulation of arachidonic acid metabolism in the perinatal brain during development and under ischemic stress. AB - Oxygen deprivation following cessation of blood flow to vital organs such as brain, heart, and kidney is a ubiquitous human disease, invariably leading to devastating consequences. Studies in experimental models support the contention that membrane permeability is altered, ion fluxes impaired, and energy stores depleted under these circumstances. Certain lipids such as diglycerides (DG) and arachidonic acid (AA), both of which are important cellular second messengers, appear to increase during ischemia. At this point, the contribution of these and other lipids to cell deregulation, loss of function, and ultimate death has not been clarified because no precise link between lipid alterations as detected in ischemia and subsequent cellular processes has been made. In this report we examine the origin of lipid-derived second messengers in fetal rat brain prelabeled with [3H]AA and study the fate of various lipids upon obstruction of the fetal-maternal circulation. The data support the possibility of a phospholipase A2-mediated deacylation of poly-phosphoinositides (poly-PI) to form free AA and a phospholipase C-mediated hydrolysis of PC to form DG during ischemia. PMID- 1636501 TI - Interactions of phospholipids and free fatty acids with antidepressant recognition binding sites in rat brain. AB - The lipid microenvironment of cell membranes has been shown to regulate both neurotransmitter and hormone receptors. Preincubation of cortical synaptosomal membranes of rat brain with phospholipase A2 (PLA2) increases the number of [3H]imipramine ([3H]IMI) high affinity binding sites without altering Kd (Bmax control: 2.53 +/- 0.28 pmol/mg protein vs Bmax PLA2: 3.66 +/- 0.26 pmol/mg protein). The displacement curves of [3H]IMI binding in synaptosomal membranes with other tricyclic antidepressants are not affected by the presence of PLA2. The effect of PLA2 was prevented by incubation with EGTA (2 x 10(-3)) or bovine serum albumin (BSA; 1:1). In addition, end products of catalytic activity of PLA2 such as unsaturated fatty acids (arachidonic or oleic acids) mimicked the effect of PLA2. These effects were entirely prevented by preincubation with BSA. The in vitro addition of the acidic phospholipid phosphatidylserine isolated from bovine brain (BC-PS) produced a similar increase in Bmax. This action was also blocked by addition of BSA. On the other hand, palmitic acid, a saturated fatty acid, and lysophosphatidylserine (lysoPS) or lysophosphatidylethanolamine (lysoPE) failed to modify [3H]IMI binding sites. The chronic administration of tricyclic antidepressant (AD) resulted in a 25% decrease in [3H]IMI binding sites in synaptosomal membranes. Preincubation of these AD-treated membranes with PLA2 did not alter [3H]IMI binding, whereas the addition of unsaturated free fatty acids (FFA) produced a greater increase in the density of [3H]IMI binding sites in comparison with control membranes. Taken together, these findings suggest that unsaturated free fatty acids could play an important role in the regulation of the number of [3H]IMI high affinity binding sites in the mammalian brain. PMID- 1636502 TI - Severe changes in polyunsaturated fatty acids in the brain, liver, kidney, and retina in patients with peroxisomal disorders. PMID- 1636503 TI - Extracellular phospholipase A2. PMID- 1636504 TI - Degradation of phospholipids and protein kinase C activation for the control of neuronal functions. PMID- 1636505 TI - Disposition kinetics of phospholipid liposomes. AB - This article reviews the disposition of intravenously injected phospholipid liposomes and discusses the problems related to its kinetic modeling. The processes responsible for the plasma clearance of liposomes are examined in detail and it is shown that mechanisms other than reversible distribution to the extravascular space are, as a rule, responsible for the biphasic plasma clearance patterns that are typically observed following bolus intravenous injection of liposomes. Accordingly, a one-compartment open model is generally sufficient to describe the disposition kinetics of phospholipid vesicles. Two factors may be responsible for the observation of a biphasic decline of plasma liposome concentration. The first factor is the presence of different liposomal species with different kinetic behaviors. Kinetically distinct vesicles are present in preparations of liposomes that are heterogeneous in size, since the larger vesicles are cleared at a faster rate than the smaller ones. Different liposomal species may also originate in the plasma as a result of: i) fusion between phospholipid vesicles with generation of larger liposomal structures; and ii) interaction with high-density lipoproteins (HDL) with consequent production of either liposomes that have acquired apoproteins or lipoprotein particles enriched in phospholipids. Both these species are cleared by specific mechanisms at rates different from that of the original vesicle. The second factor is a time dependent decrease in clearance due to progressive saturation of the retention capacity of the cells that take up liposomes. A convex concentration-time decay curve has also been reported. This decay pattern is consistent with a concentration (dose)-dependent elimination. As this observation relates to only one type of liposome (small unilamellar vesicles composed of sphingomyelin and cholesterol), its relevance to the disposition of liposomes of different size and composition remains to be established. PMID- 1636506 TI - Ischemic brain damage: focus on lipids and lipid mediators. AB - The last two decades of research have produced detailed information not only on how ischemia causes degradation of phospholipids and accumulation of potentially cytotoxic breakdown products of such lipids, but also on reactions elicited by the subsequent conversion of these products into a series of lipids, mediating an array of cellular and intercellular reactions. It now seems clear that PAF, as well as several of the cyclooxygenase and lipoxygenase products of arachidonic acid, can induce changes, particularly in the microvasculature, which jeopardize cell survival in reperfused tissue. It is equally clear that, at least following long periods of ischemia, free radicals generated in reactions that are interacting with those producing eicosanoids and PAF play a similar role. A somewhat more speculative mechanism links sustained activation and membrane translocation of PKC to delayed neuronal death following transient ischemia. All of these interactions underscore the importance of lipolytic events for cell damage in ischemia and other conditions with a compromised cellular energy metabolism. PMID- 1636507 TI - Diacylglycerol composition and metabolism in peripheral nerve. AB - The content and molecular species composition of 1,2-diacylglycerol (DAG) in rat sciatic nerve was determined and compared with the molecular species profiles for glycerophospholipid classes in order to gain information concerning the metabolic pathways of DAG formation. The level of DAG in freshly dissected epineurium-free nerve (44 +/- 2 pmol/mg wet weight) was 10-40% of that in other tissues and cultured cells. The predominant DAG molecular species were 18:0/20:4 (30%) and 16:0/18:1 (17%). In comparison with phospholipid molecular species patterns, DAG was characterized by a substantial but lower proportion of the 18:0/20:4 species than was found in phosphoinositides, and a significant fraction of saturated species such as those found in phosphatidylcholine. In nerve from diabetic rats, both the content and arachidonoyl-containing molecular species of DAG were reduced. These species were also decreased in individual glycerophospholipids, except for phosphatidylinositol. The distribution of molecular species in phosphatidic acid (PA) did not resemble that of any other phospholipid. A large rise in DAG content occurred when nerve was incubated in vitro. Molecular species analysis indicated that phosphoinositides were the main source, especially during the initial period. This process was virtually abolished in a Ca(2+)-free medium and probably reflects a response to tissue injury. Evidence was obtained for the isomerization of DAG to 1,3-diacylglycerol during incubation. PA content and molecular species composition of incubated nerve did not change. However, inclusion of propranolol, a PA phosphatase inhibitor, caused a 40% accumulation of PA within 10 min, suggesting that formation of this phospholipid is continuous. These findings support the conclusion that DAG is principally derived from phosphoinositides by phospholipase C hydrolysis, but a minor fraction could be derived from phosphatidylcholine either by the action of phospholipase C or via phospholipase D and PA phosphatase. The metabolic origins of PA appear to be diverse. PMID- 1636508 TI - Physiology of osmotolerance in fungi. PMID- 1636509 TI - Yeast flocculation: a new perspective. PMID- 1636510 TI - Crystalline bacterial cell-surface layers. PMID- 1636511 TI - Bacterial motility and chemotaxis. PMID- 1636512 TI - Secretory pathway function in Saccharomyces cerevisiae. AB - A genetic analysis of secretory pathway function in yeast was initiated some 12 years ago in the laboratory of Randy Schekman. These mutants held great promise in terms of providing an experimental system with which molecular participants of secretory pathway function could be investigated. This early promise has not failed. For the last five years, analysis of yeast secretory pathway function has been at the cutting edge of our understanding of the mechanisms by which proteins travel between intracellular compartments. In some cases, Sacch. cerevisiae has provided a valuable in vivo corroboration of the concepts derived from biochemical studies of mammalian intercompartmental protein transport in vitro. In other cases, studies conducted in the yeast system have defined previously unanticipated involvements for known catalytic activities in the secretory process. It is clear that yeast will continue to play a major role in setting the pace of research directed towards a detailed molecular understanding of protein secretion. Since it is now apparent that the basic strategies that underlie secretory pathway function have been conserved among eukaryotes, further exploitation of the powerful and complementary yeast and mammalian experimental systems guarantees that the next decade will see even greater progress towards our understanding of protein secretion in eukaryotic cells than did the first. PMID- 1636513 TI - MR imaging in radiation myelopathy. AB - PURPOSE: Using MR imaging, we assessed the signal, size, and enhancing characteristics of the cervical cord in patients in whom radiation myelopathy developed after radiotherapy for nasopharyngeal carcinoma. PATIENTS AND METHODS: Ten patients, 3 men and 7 women, aged from 32 to 77 years, were included. MR imaging was performed 1 to 53 months after clinical manifestations of myelopathy. RESULTS: Two cases showed atrophy of the cervical cord without abnormal signal intensity; in the others, a long segment of the cervical cord demonstrated low signal intensity on T1-weighted images and high signal intensity on T2- or T2* weighted images. Some of these cases also showed swelling of the cord. Focal enhancement at C1-C2 area after intravenous administration of Gd-DTPA was seen in four cases. CONCLUSIONS: There is a correlation between the time of MR imaging after onset of symptoms and MR findings. When MR scans were obtained more than 3 years after onset of symptoms, atrophy of the cervical cord was noted without abnormal signal intensity. When MR was performed less than 8 months after onset of symptoms, a long segment of the cervical cord demonstrated abnormal signal intensity with or without associated swelling of the cord and focal enhancement. PMID- 1636514 TI - Ossification of the posterior longitudinal ligament: MR evaluation. AB - PURPOSE: To investigate the MR appearance of ossification of the posterior longitudinal ligament (OPLL) of the cervical spine. MATERIALS AND METHODS: A retrospective review of MR images and conventional tomograms in 147 patients. RESULTS: In the sagittal plane, proton-density images identified the ossified lesions more clearly than did T1- and T2-weighted images. All axial sequences identified the lesions much frequently. T1-weighted images often showed areas of increased intensity within the lesions of the continuous and mixed type, especially within the thick lesions. Fat images by Dixon technique demonstrated same areas of increased intensity, which strongly suggested fatty marrow formation. On conventional tomograms, configurations of radiolucent areas within the lesions corresponded to areas of increased intensity on T1-weighted images. CONCLUSION: Proton-density sagittal and axial images are important in establishing the diagnosis of OPLL. The areas of increased intensity on T1 weighted images and radiolucent areas suggest marrow formation. PMID- 1636515 TI - Spinal MR findings in neurofibromatosis types 1 and 2. AB - PURPOSE: To evaluate the frequency and nature of spinal pathology, the frequency of clinically silent lesions, and the potential benefit of screening spinal MR in neurofibromatosis patients. PATIENTS AND METHODS: 28 neurofibromatosis type-1 (NF 1) patients and nine neurofibromatosis type-2 (NF-2) patients were studied with postcontrast spinal MR imaging. RESULTS: NF-1: One patient had a biopsy-proven low-grade glioma; five patients, intradural, extramedullary masses (N = 23); one patient, extradural masses (N = 2) (neurofibromas); 16 patients had bony abnormalities; and three patients thecal sac abnormalities. NF-2: Five patients demonstrated intramedullary masses (five/eight ependymomas); nine patients, intradural, extramedullary masses (meningiomas, schwannomas); and four patients, bony abnormalities. Eight/10 NF-1 and four/nine NF-2 patients had asymptomatic masses. CONCLUSION: Intradural disease is common, often asymptomatic, and often presents at a young age in NF-1 and NF-2 patients. Because of the propensity to develop significant asymptomatic as well as symptomatic intradural disease, screening of the entire spine with MR is recommended in both NF-1 and NF-2 patients. PMID- 1636516 TI - Radiologic screening in the neurocutaneous syndromes: strategies and controversies. PMID- 1636517 TI - Meningocele manque: radiologic findings with clinical correlation. AB - PURPOSE: To determine whether meningocele manque can be detected by neuroimaging techniques in dysraphic patients. METHODS: We reviewed the records and imaging studies of 16 patients with surgically proved meningocele manque seen at our institution between 1989 and 1990. Both CT and MR imaging techniques were used. CT of the spine was performed immediately following contrast myelography. RESULTS: Nine of 16 patients (CT, four; and MR, five) showed evidence of meningocele manque which corresponded to intraoperative findings. Fourteen of 16 patients were found to have diastematomyelia, eight with medium septum and six without a septum. Associated findings included syrinx (six), lipoma (five), dermoid cyst (one), and neuroenteric cyst (one). After completing this review, we were able to prospectively diagnose dorsal bands in two new patients; these bands were confirmed at surgery. CONCLUSION: Dorsal bands can be detected in dysraphic patients with CT or MR using operative findings as a road map. PMID- 1636518 TI - Aneurysm hemodynamics: an experimental study. AB - PURPOSE: To study the flow of blood in aneurysms. METHODS: A canine model was used to study the hemodynamics of lateral, bifurcation, and terminal aneurysms with angiography and color Doppler techniques. FINDINGS: Flow within experimental aneurysms, although not laminar, is seldom if ever turbulent, but rather is highly predictable, varying primarily according to the relationship of the aneurysm to its parent artery. CONCLUSIONS: These studies support earlier in vitro work and provide further evidence that not all aneurysms share similar stresses. A more complete understanding of these hemodynamic features will be useful in the establishment of criteria that allow recognition of those aneurysms that are more or less likely to rupture, to grow, or to thrombose. PMID- 1636519 TI - MR diffusion imaging of cerebral infarction in humans. AB - PURPOSE: MR diffusion imaging was performed to investigate changes in water diffusion in patients with cerebral infarction. METHODS: Diffusion maps of the apparent diffusion coefficient (ADC) were created to show local water mobility in the brain tissue in 15 patients. These ADC maps were compared with conventional T2-weighted images. RESULTS: Distinct subregions with different water diffusions were detected, even when the infarcted area appeared homogeneous on a T2-weighted image. The results also show that stroke lesions of the same age can have very different water diffusions. A trend towards an increasing diffusion coefficient in a lesion during the first several days following an acute event was observed in a group of patients imaged at multiple timepoints. CONCLUSION: The measurement of diffusion coefficients in vivo now offers an opportunity for greater understanding of the biophysical changes that occur during the evolution of infarction in humans. PMID- 1636520 TI - Stereotaxic angiography in gamma knife radiosurgery of intracranial arteriovenous malformations. AB - Gamma knife radiosurgery is an effective alternative to embolization or microsurgical removal of small arteriovenous malformations, particularly in eloquent areas of brain tissue. Stereotaxic angiography is a useful diagnostic and targeting adjunct to gamma knife radiosurgery, and the authors present their experience (1,100 patients) with methods and technique, and show how the nidus of the arteriovenous malformation can be defined angiographically. Dose planning employing digitization of the subtraction image enables determination of the spatial coordinates of the lesion by means of an interactive computer program. PMID- 1636521 TI - Cerebral aneurysms: detection and delineation using 3-D-CT angiography. AB - PURPOSE: We compared three-dimensional image (3-D-CT) angiography with conventional angiography to determine the clinical usefulness of this technique. MATERIALS AND METHODS: We studied 15 patients with cerebral aneurysms using dynamic CT with intravenous injection of contrast material and reconstructed 3-D CT angiography. RESULTS: 3-D-CT angiography could be performed in conjunction with standard axial high-resolution CT without any additional scanning time and within 10-30 minutes for the overall study. All aneurysms were clearly visualized by 3-D-CT angiography. 3-D-reconstruction was very helpful in demonstrating the neck, shape, and direction of aneurysms, and adjacent vascular and bony structures. One small aneurysm that was difficult to detect on axial images was clearly visualized on 3-D-reconstruction. CONCLUSION: 3-D-CT angiography of cerebral aneurysms could be performed routinely and was helpful in demonstrating the complex anatomy of cerebral aneurysms and surrounding structures. This technique will be of value in surgical planning. PMID- 1636522 TI - Raeder syndrome: MR appearance. AB - A 40-year-old woman presented with symptoms compatible with Raeder syndrome. MR demonstrated narrowing of the left cavernous carotid artery. The high cervical portion of the left internal carotid artery was not identified. Angiography confirmed the narrowing of the cavernous carotid artery and showed marked and irregular stenosis of the distal cervical internal carotid artery. Involvement of the left sympathetic plexus and of ipsilateral cavernous sinus arteries is believed to have been the cause of the Raeder syndrome in this patient. PMID- 1636523 TI - Noninvasive preoperative cortical localization by magnetic source imaging. AB - The authors successfully used magnetoencephalography and MR data to localize the sensorimotor cortex in two patients prior to neurosurgery; preoperative localization influenced surgical management. PMID- 1636524 TI - Three-dimensional time-of-flight MR angiography in the evaluation of intracranial aneurysms treated by endovascular balloon occlusion. AB - The authors share their experience with MRA in the assessment of cerebral aneurysms. Despite its limitations--spatial resolution, insensitivity to slow flow states, subacute thrombus artifacts--they believe the technique shows potential. PMID- 1636525 TI - Acute thrombosis of the intracranial dural sinus: direct thrombolytic treatment. AB - Acute intracranial dural sinus thrombosis may have severe morbidity or fatal complications without appropriate treatment. Direct dural sinus venography can be performed safely with a soft Tracker catheter to document the fresh thrombus as an adjunct to CT or MR. We are reporting our experience with successful direct urokinase thrombolytic therapy in three cases of superior sagittal sinus and two cases of transverse and sigmoid sinus thrombosis. All five patients have recovered completely without any residual clinical deficit. PMID- 1636526 TI - Professor Giovanni Di Chiro, Director of Neuroradiology at the National Institutes of Health in Bethesda, Maryland, was the recipient of the "Ottorini Rossi Award". PMID- 1636527 TI - Endovascular treatment of a giant fusiform aneurysm of the entire basilar artery. AB - The authors describe a case of fusiform basilar artery aneurysm not amenable to surgical clipping or balloon occlusion with preservation of the parent artery. The aneurysm was treated by balloon occlusion (proximal basilar artery) after test occlusion was well-tolerated; 7-year follow-up showed good results. PMID- 1636528 TI - Internal carotid balloon test occlusion does require quantitative CBF. PMID- 1636529 TI - Asymmetric appearance of intracranial vessels on routine spin-echo MR images: a pulse sequence-dependent phenomenon. AB - PURPOSE: To determine the cause of right to left signal intensity differences arising from intracranial vessels during routine spin-echo axial MR imaging of the head. METHODS AND RESULTS: Using a normal imaging sequence in which the default directions of the frequency and phase axes were horizontal and vertical, respectively, differences in signal intensity arising from the vertebral arteries were observed in a healthy subject. With the exchange of the frequency and phase axes relative to the normal sequence, no signal intensity differences between the vertebral arteries were recognized. Other pulse sequence modifications, ie, the use of motion-compensating gradients and the reversed polarity of the frequency encoding gradient, also resulted in variable appearances of the vertebral arteries, indicating that the right-to-left signal asymmetry of the vertebral arteries observed on the normal spin-echo image results from a pulse sequence dependent phenomenon. CONCLUSIONS: Frequency-encoding and slice-selection gradients both produce motion-induced phase shifts. These phase shifts depend on the angle between the direction of flow and that of the effective vector sum of these gradients. The asymmetric appearance of the vertebral arteries during normal spin-echo imaging was found to result from the angle dependence of motion induced phase shifts. Awareness of this artifactual phenomenon is important to avoid confusing it with conditions such as stenosis/occlusion, dissection, or slow flow. PMID- 1636530 TI - Endoscopic paranasal sinus surgery: radiographic evaluation of severe complications. AB - PURPOSE: To report our experience with the radiographic evaluation of severe complications resulting from the functional endoscopic sinus surgery (FESS) procedure. PATIENTS: Ten major complications were reviewed retrospectively. FINDINGS: Ten major complications occurred. Eight of 10 had injury to the floor of the anterior cranial fossa, fovea ethmoidalis (roof of the ethmoid sinus), or roof of the sphenoid sinus. Six patients presented with meningitis or rhinorrhea, two presented with headache and massive pneumocephalus; one patient who presented with meningitis had a large nasal frontal encephalocele. Noncontrast brain CT that included the paranasal sinuses adequately evaluated the source of pneumocephalus. Thin-section coronal CT accurately predicted the site of leak in five patients. Both coronal sinus CT and MR imaging were useful to confirm the nasal encephalocele. Two of 10 had vascular injury secondary to FESS. One patient presented with subarachnoid hemorrhage seen on noncontrast CT and cerebral angiography demonstrated an aneurysm of the anterior cerebral artery. The second patient suffered severe intraoperative hemorrhage. Emergency angiography revealed a pseudoaneurysm of the cavernous carotid artery, and balloon occlusion of the artery was performed. No deaths occurred in this series. CONCLUSION: Radiologists should be familiar with the rare, but potential complications of this commonly performed procedure in order to help direct the work-up in an efficacious manner. PMID- 1636531 TI - Rapid MR imaging of the pediatric brain using the fast spin-echo technique. AB - PURPOSE: To evaluate diagnostic reliability and to establish optimal scanning techniques of a recently developed Fast Spin-echo MR pulse sequence that allows rapid proton density-weighted and T2-weighted imaging. METHODS: We compared lesion conspicuity and signal intensity measurements on Fast Spin-echo and conventional spin-echo sequences in 81 patients ranging from 1 week to 25 years in age on a 1.5-T MR unit. A total of 28 Fast Spin-echo dual-echo images (14 slice locations) were obtained in 2:08 minutes with a 256 x 128 matrix or in 3:12 minutes with a 256 x 192 matrix at a TR of 2000 msec and two excitations. RESULTS: Lesion conspicuity and characterization on Fast Spin-echo images compared favorably with conventional spin-echo images in our series when pseudo TEs of 15 and 90 msec were employed for proton density-weighted and T2-weighted images, respectively. Fast Spin-echo images yielded diagnostic information in four nonsedated patients whose conventional spin-echo images were either degraded by motion or unobtainable. Fat signal remained bright on T2-weighted Fast Spin echo images. Magnetic-susceptibility effects were slightly reduced with Fast Spin echo but did not pose any diagnostic problem in our series. CONCLUSION: Diagnostically reliable rapid dual-echo brain images can be obtained with Fast Spin-echo sequences. PMID- 1636532 TI - Bilateral neonatal Sturge-Weber-Dimitri disease: CT and MR findings. AB - The CT and MR features of cortical calcification and meningeal angiomatosis are typical of Sturge-Weber-Dimitri disease but are unusual in children less than 1 year of age. This case describes a child presenting with both of these features bilaterally in the neonatal period and represents an unusual presentation of this disorder. PMID- 1636533 TI - High signal from the otic labyrinth on unenhanced magnetic resonance imaging. AB - High signal from the otic labyrinth was observed on precontrast MR scan of two patients who presented with sudden hearing loss and vertigo. The authors suggest the possibility that the high signal was caused by hemorrhage but that clinical significance and therapeutic implications of this finding need further study. PMID- 1636534 TI - MR appearance of intracanalicular eighth nerve lipoma. AB - The authors present the MR appearance of an intracanalicular eighth nerve lipoma in a 30-year-old woman, describe the clinical manifestations, and discuss the possible etiology; biopsy findings were conclusive. Precontrast T1-weighted images should be obtained. PMID- 1636535 TI - CT and ultrasound imaging of retropharyngeal abscesses in children. AB - PURPOSE: To show the role of ultrasound (US) in distinguishing retropharyngeal abscess from adenitis in children. METHODS: Eleven infants and children had clinical symptoms suggestive of retropharyngeal infection. Radiographic evaluation included, lateral neck radiography (11/11), contrast-enhanced neck CT (10/11), contrast-enhanced neck MR (1/11), and real time US (11/11) patients. US was used to characterize masses as solid (adenitis) or complex (abscess) and for guiding intraoperative aspiration and drainage. RESULTS: Contrast CT and MR showed findings suspicious for abscess in all 11 cases. Only three children had surgically drainable abscesses. CT numbers within inflammatory masses did not distinguish adenitis from abscess. US was able to correctly diagnose abscess or adenitis in each case. CONCLUSION: Lateral neck radiography and contrast CT identify and localize retropharyngeal inflammatory masses in children. US, but not CT, distinguishes between adenitis and abscess and aids in intraoperative aspiration and drainage. PMID- 1636536 TI - MR imaging in patients with primary thyroid lymphoma. AB - The authors describe two patients with thyroid lymphoma and Hashimoto thyroiditis; T1- and T2-weighted MR sequences were used. In one patient, the region of lymphoma showed a different signal intensity on T2 images; in the other patient, the signal level was identical to the Hashimoto disease. In sum, the processes could not be significantly differentiated using MR. PMID- 1636537 TI - Administration of gadopentetate dimeglumine in MR imaging of intracranial tumors: dosage and field strength. AB - PURPOSE: To investigate the efficacy of 0.025, 0.05 and 0.1 mmol/kg gadopentetate dimeglumine in MR imaging of patients with intracranial tumors at mid and high field strength. METHODS: In 88 patients, an open-label phase III multicenter dose finding study was performed at 0.5, 1.0, and 1.5 T MR units. Before and after (5, 15, 25 minutes) intravenous administration of gadopentetate dimeglumine, imaging was performed with T1-weighted spin-echo sequences. RESULTS: With 0.1 mmol/kg yielding the highest values, tumor enhancement and numerical tumor/brain contrast showed dose-dependent 5-minute postcontrast values (P less than 0.05). Compared to 5-minute postcontrast values, there was no significant change at 15 and 25 minutes. Although the lowest values of enhancement were found at 0.5 T, differences in enhancement among the field strengths were not statistically significant. The numerical data were confirmed by visual assessment of tumor/brain contrast. Eighty to 90% of cases had diagnostically valuable enhancement at 0.1 mmol/kg, 50% at 0.05 mmol/kg, and 10% at 0.025 mmol/kg (P less than 0.05). There were no adverse events. CONCLUSION: Our results confirm that 0.1 mmol/kg gadopentetate dimeglumine is more effective at enhancing intracranial tumors than lower doses at mid and high field MR units. PMID- 1636538 TI - MR of primary CNS lymphoma in immunologically normal patients. AB - PURPOSE: To describe the MR findings of primary CNS lymphoma. METHODS: MR scans of 20 patients with histologically proved primary CNS lymphoma were reviewed. We evaluated the size, multiplicity, signal intensities, and enhancement characteristics of the lesions. We divided the lesions into an enhancing area referred to as Zone 1 and abnormal signal surrounding this, referred to as Zone 2. RESULTS: Primary CNS lymphoma presented as solitary enhancing lesions in 40% of the patients and multiple lesions in 40%. Thirty-three separate lesions were visible: 58% abutted the ventricular system, 76% showed a homogenous enhancement pattern, and 79% showed marked enhancement. In 64% of the lesions, Zone 1 and Zone 2 showed different signal intensities on T1-weighted images. CONCLUSIONS: Primary CNS lymphoma usually presents as solitary or multiple dense homogenous enhancing lesions that abut an ependymal surface. These lesions can be divided into an enhancing area and an area of surrounding abnormal signal. These two areas often have different signal intensities on unenhanced T2-weighted images. These findings are sufficiently suggestive of the diagnosis of primary CNS lymphoma that a needle biopsy be performed based on these findings and appropriate therapy can then be instituted. PMID- 1636539 TI - Neuromas and meningiomas: evaluation of early enhancement with dynamic MR imaging. AB - PURPOSE: To investigate the role of dynamic MR imaging in the differentiation of neuromas and meningiomas. METHODS: Eleven patients with neuromas and 15 patients with meningiomas underwent dynamic contrast-enhanced MR imaging using a short TE FLASH sequence and a bolus injection of Gd-DTPA. RESULTS: There was no significant difference between these tumors in the signal-enhancement increment at the late phase, which corresponds to the signal-enhancement increment between pre- and postcontrast images in conventional spin-echo imaging. However, the signal enhancement at the vascular phase, ie, the phase where the first passage of Gd-DTPA was recognized both in the arteries and veins, was approximately four times as high in meningiomas as in neuromas. The difference was statistically significant. Furthermore, meningiomas had a wider range of early signal enhancement than did neuromas, reflecting the histologic varieties: two angioblastic meningiomas had the highest values, and three fibroblastic the lowest values comparable with those of neuromas, while meningiomas with other subtypes had intermediate values. CONCLUSIONS: The results of this study indicate that the evaluation of early enhancement with dynamic MR imaging is helpful in the differentiation of neuromas and meningiomas, and possibly in the crude prediction of pathologic subtypes of meningiomas. PMID- 1636541 TI - Bilateral thalamic glioma: review of eight cases with personality change and mental deterioration. AB - PURPOSE: To describe the clinical, radiographic, and neuropathologic features of bilateral thalamic glioma. METHODS: We searched our hospital records (1963 to present) to identify patients diagnosed as having the disease. RESULTS: Our search revealed eight patients, ranging in age from 8-63 years, with bithalamic tumor diagnosed by angiography, CT, and/or MR. All patients displayed personality changes and/or mental deterioration, including memory loss, inattention, confusion, hallucination, hyperphagia, or slow mentation. Unilateral motor weakness was also noted in six cases. The tumor always involved the medial aspect of the left and right thalami, but was often more extensive. The pathology was determined to be grades I-IV astrocytoma, confirmed by stereotactic biopsy or autopsy in six. Mild to moderate hydrocephaly occurred in some cases and was considered to be a contributing factor to mental deterioration. No correlation was found between age and type of tumor. CONCLUSIONS: Bilateral glioma of the dorsomedial and intralaminar nuclei of the thalamus can be a primary cause of dementia that has not been well-recognized in the past. CT and particularly MR should be considered for patients presenting with personality change or dementia, because of the possible presence of this unusual but devastating disease. PMID- 1636540 TI - MR imaging of metastatic GI adenocarcinoma in brain. AB - PURPOSE: To investigate an observed preferential T2-shortening effect seen in patients with intracerebral metastases from adenocarcinoma of the GI tract. METHODS: Ten patients with intracerebral metastases from adenocarcinoma of the GI tract were evaluated with MR imaging with CT and histopathologic correlation. RESULTS: Nine of 10 patients demonstrated intracranial masses with decreased signal intensity on T2-weighted images. T1-weighted images showed decreased or isointense signal in all cases. Special histologic staining was performed in four of 10 cases, all of which were positive for increased protein (mucin) with no evidence of blood products or calcium. CONCLUSION: We propose that the observed preferential T2-shortening effect is secondary to slowing of rotational and translational proton motion caused by increased protein concentration in the form of mucin. PMID- 1636542 TI - Prospective cerebral MR study of HIV seropositive and seronegative men: correlation of MR findings with neurologic, neuropsychologic, and cerebrospinal fluid analysis. AB - PURPOSE: As part of a longitudinal study of human immunodeficiency virus type 1 (HIV) infection, we attempted to identify early cerebral MR findings that might correlate to clinical evidence of central nervous system involvement. METHODS: We studied 65 seropositive and 40 seronegative homosexual males using cranial MR, neurologic, immunologic, and neuropsychologic examinations. RESULTS: The incidence of mildly enlarged ventricles, sulci, and punctate areas of abnormal signal in both groups was similar in both groups. Diffuse, poorly defined areas of abnormal white matter signal were difficult to consistently identify in seropositives. Enlarged adenoidal lymphoid tissue was found in 30 (46%) of seropositives and 2 (5%) of seronegatives (P = .0001). The incidence of sinus inflammatory change was similar in the two groups. CONCLUSION: MR of intracranial contents is substantially normal in a non-AIDS HIV(+) population. PMID- 1636543 TI - MR findings in acute and chronic coccidioidomycosis meningitis. AB - PURPOSE: To characterize MR findings in acute and chronic coccidioidomycosis meningitis and relate the imaging features to the clinical course. METHODS: We reviewed MR scans and clinical findings of 12 patients with coccidioidal meningitis. RESULTS: Patients with active or untreated disease were found to have hydrocephalus and intense enhancement of the cervical subarachnoid space, basilar, sylvian, and interhemispheric cisterns on postcontrast MR scans. Focal parenchymal signal abnormalities suggesting ischemia or infarction were common. Abnormal MR enhancement decreases during therapy, although patients develop cortical and/or brain stem atrophy. CONCLUSIONS: Widespread cisternal and cervical subarachnoid meningeal involvement is common in coccidioidal meningitis. Serial contrast MR imaging reflects the effects of therapy in patients with coccidioidal meningitis. PMID- 1636544 TI - MR imaging of intraventricular cysticercosis. AB - Intraventricular cysticercosis cysts can migrate through the ventricular system and produce hydrocephalus. MR is more sensitive than CT in the detection of these cysts. PMID- 1636545 TI - Simultaneous neurofibroma and schwannoma of the sciatic nerve. AB - The authors report a case of simultaneously occurring neurofibroma and schwannoma of the sciatic nerve and discuss the complementary aspects of MR and US. The schwannoma was well-defined and showed distal enhancement on sonographic evaluation, whereas the neurofibroma was ill-defined; both tumors were hypoechoic. T1- and T2-weighted MR images revealed similar signal characteristics of the two tumors, but intense enhancement following administration of gadolinium DTPA distinguished the schwannoma from the neurofibroma. PMID- 1636546 TI - Orbital mesenchymal chondrosarcoma. PMID- 1636547 TI - Gadopentetate dimeglumine enhancement of multiple sclerosis lesions on long TR spin-echo images at 0.6 T. AB - The authors sought to determine if Gd-DTPA enhancement of multiple sclerosis (MS) hampers lesion detection on long TR spin-echo images (TE 60 msec) at 0.6 T. They measured the signal intensity (SI) of 41 lesions (10 patients) and normal appearing gray (NAGM) and white matter (NAWM) before and after administration of contrast. The change in SI of nonenhancing lesions and NAGM and NAWM was small (less than or equal to 1.5%), and of enhancing lesions (5.3%) moderate. The contrast of nonenhancing lesions to NAGM and NAWM changed insignificantly, but the contrast of enhancing lesions to NAGM and NAWM increased significantly. The authors conclude that long TR images can be obtained after Gd-DTPA without hampering lesion conspicuity in research MR protocols in multiple sclerosis. PMID- 1636548 TI - Chondromyxoid fibroma of the frontal bone. AB - Chondromyxoid fibroma of frontal bone is a rare lesion. Plain skull films showed a round radiolucent mass with a sclerotic margin. It was dense on plain CT scan and showed no convincing contrast enhancement. MR imaging showed low signal intensity relative to gray matter on T1-weighted image (500/20), isointensity on proton-density image (2000/30), high intensity on T2-weighted image, and marked peripheral enhancement on postcontrast (gadopentetate dimeglumine) study. PMID- 1636550 TI - Contrast-enhanced CT of acute isodense subdural hematoma. PMID- 1636549 TI - Postoperative dissemination of fat particles in the subarachnoid pathways. AB - A case of postoperative dissemination of fat particles into the cerebrospinal fluid pathways is reported. Following removal of a foramen magnum meningioma, a postoperative MR scan showed fat droplets in the basal cisterns and in the frontal horns of the lateral ventricles. The patient was asymptomatic and a repeat MR scan 7 months later was normal, with resolution and clearing of the previously noted cerebrospinal fluid fat. PMID- 1636551 TI - Unusual MR and CT appearance of an epidermoid tumor. PMID- 1636552 TI - The spectrum of radiologic abnormalities in the neonatal CNS. PMID- 1636553 TI - Physician integrity and the bureaucracy. PMID- 1636554 TI - Sticker shock. PMID- 1636555 TI - Exemption from seat belt use. PMID- 1636556 TI - Syndrome of 'iatrogenic' polydipsia. PMID- 1636557 TI - Preterm birth prevention: cognition over technology? PMID- 1636558 TI - Family physicians and social responsibility. PMID- 1636559 TI - Diary from a week in practice. PMID- 1636560 TI - Preventing the complications of preterm birth. AB - Preterm birth is a major cause of infant morbidity and mortality. Although studies have been complicated by problems of definition and methodology, certain strategies have the potential to reduce both the incidence and the impact of preterm birth. These strategies include accurate assessment of gestational age, education about the signs and symptoms of early labor, recommendations for smoking cessation, and screening for asymptomatic bacteriuria in all prenatal patients. In addition, specific interventions such as cervical cerclage may be indicated in certain patients. The role of home uterine monitoring is not yet established. If preterm labor does occur, tocolysis should be used to delay delivery, and in appropriate cases the patient should be transferred to a medical center with a neonatal intensive care unit. Antenatal administration of corticosteroids in preterm labor appears to significantly reduce fetal morbidity. PMID- 1636561 TI - Traumatic rupture of the diaphragm and herniation of the liver. AB - Injuries that result in a sudden increase in intra-abdominal pressure may cause a diaphragmatic tear and visceral herniation. Right-sided tears are significantly less likely than left-sided tears because of the protective effect of the liver. When diaphragmatic elevation persists in a post-trauma patient, or if unexplained acidosis or hypoxemia develops, herniation of abdominal contents should be suspected. This is particularly true when other signs of severe trauma are present, such as multiple rib fractures, laceration of the liver or spleen, or a history of deceleration injury. PMID- 1636562 TI - Intraoral examination in pyogenic facial lesions. AB - Pyogenic cutaneous lesions of the cervicofacial region may be due to a variety of causes. One possibility that should be considered is an odontogenic infection secondary to untreated dental caries, periodontal disease or previous maxillofacial trauma. An intraoral examination is mandatory to evaluate the oral cavity for signs of pathology that may be manifested as a purulent cutaneous lesion. Patients with odontogenic infection should be referred to a dentist for definitive treatment, which may consist of either endodontic therapy or extraction of the involved tooth and curettage of any abscesses or fistulous tracts. PMID- 1636563 TI - Acute pain management in infants, children and adolescents: operative and medical procedures. Agency for Health Care Policy and Research. PMID- 1636564 TI - Trichloroethylene: environmental and occupational exposure. AB - Trichloroethylene is used in paint strippers, rug cleaners, spot removers, typewriter correction fluid and industrial cleaners. It is a common environmental contaminant, detected in over one-third of hazardous waste sites and in 10 percent of groundwater sources. Acute workplace exposure above acceptable levels can cause neurologic, respiratory and hepatic problems. The health effects of prolonged occupational and environmental low-level exposure are probably minimal, but whether such exposure poses a risk remains controversial. Although trichloroethylene has been shown to cause cancer in some animals, it has not been proven to be a human carcinogen. Trichloroethylene has been involved in several well-publicized cases of contamination of community water supplies, and family physicians are likely to receive questions about this chemical. PMID- 1636565 TI - Loop electrosurgical excision procedure for CIN. AB - The loop electrosurgical excision procedure, also referred to as large loop excision of the transformation zone, is gaining acceptance in the United States as a method for treating cervical intraepithelial neoplasia. Loop excision of cervical tissue is accomplished using a high-frequency alternating current (radiofrequency) and thin wire loop electrodes. Loop excision may be in the form of simple excision of the transformation zone or electrosurgical loop conization. The specimens obtained using this technique are suitable for histologic evaluation. Loop excision, which is usually performed under local anesthesia, is associated with minimal short-term and long-term morbidity. Patient acceptance is high. Family physicians who perform colposcopy should consider using loop electrosurgical excision to treat cervical intraepithelial neoplasia in the outpatient setting. PMID- 1636567 TI - Concurrent HIV and HCV infections hasten liver failure. PMID- 1636568 TI - ACOG (American College of Obstetricians and Gynecologists) issues report on HIV infection in women. PMID- 1636566 TI - Jimson weed toxicity: management of anticholinergic plant ingestion. AB - Jimson weed is a hallucinogenic plant that is common in rural areas. Consumption of any part of the plant can result in severe anticholinergic toxicity. The clinical presentation of jimson weed toxicity is similar to that seen in cases of atropine poisoning. Treatment is aimed at removing plant material from the gastrointestinal tract, keeping the patient safe and reversing severe anticholinergic sequelae. PMID- 1636569 TI - FDA approval of rapid HIV test. PMID- 1636570 TI - Approval of ddC for AIDS patients. PMID- 1636571 TI - Left ventricular function under stress before and after myocardial revascularization. AB - To compare left ventricular responses to stress during exercise-induced myocardial ischemia and after myocardial revascularization, 35 patients (mean age 55 +/- 7 years, class III angina) with three-vessel coronary artery disease underwent a rest and exercise initial-transit radionuclide angiocardiography before aortocoronary bypass grafting. Left ventricular ejection fraction decreased during exercise (p less than 0.01), but cardiac output was augmented with an increased heart rate (p less than 0.0001) and left ventricular end diastolic volume (p less than 0.001). Group A (n = 15) underwent six serial resting studies at different volume loads during the first 24 hours after operation while heart rate and blood pressure were held constant. These data revealed no significant change in left ventricular ejection fraction, but preload varied in all patients because of bleeding and fluid administration, with a mean end-diastolic volume change of 115 to 176 ml. This range of end-diastolic volume was similar to that defined with rest and exercise testing before operation. Group B (n = 20) underwent a repeat rest and exercise test 3 months after operation that demonstrated no change in resting function. However, exercise ejection fraction and peak systolic pressure/end-systolic volume ratio increased (p less than 0.001 and p less than 0.05, respectively) while end-diastolic volume decreased (p less than 0.05) compared with the values before operation. These data indicate that patients with coronary artery disease have chronically adapted cardiac function that makes use of both rapid heart rate and a wide range in preload to augment cardiac function under stress.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636572 TI - Detection of acute myocardial infarction with digital image processing of two dimensional echocardiograms. AB - We have previously described the ability of a computer-based image digitizing system to assess early textural changes in acute canine myocardial infarction. To determine whether this technique could be applied to human beings, we studied 12 patients with a first acute transmural myocardial infarction and five normal subjects. Two-dimensional echocardiograms were performed on days 1 and 8 in normal subjects and on days 1 (day of admission), 2, 3, 5, and 14 in the patient population. All recording parameters on the echocardiography machine were kept identical for serial studies. The mean period between hospitalization and first echocardiogram was 11.1 hours (range 4 to 20 hours). End-diastolic frames from the two-dimensional echocardiographic images were digitized and displayed on a monitor. The mean pixel intensity (MPI) (+/- SD) in the region of asynergy (area of myocardial infarction) and a normal area were determined. In normal volunteers, no significant change in MPI was noted between anteroseptal and lateral areas on two separate two-dimensional echocardiographic studies, which were performed 7 days apart (anteroseptal: MPI, 21.6 +/- 1.1 vs 21.8 +/- 0.4, p = not significant) and (lateral: MPI, 21.5 +/- 1.2 vs 21.4 +/- 1.4, p = not significant). In patients with myocardial infarction, a significant increase in MPI was noted on the first day of myocardial infarction between normal and infarcted myocardium (20.4 +/- 2.0 vs 24.3 +/- 2.3, p less than 0.05) and progressively increased thereafter until day 14 (20.5 +/- 1.7 vs 31.9 +/- 3.7, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636573 TI - Quantitative planar imaging of glucose metabolic activity in myocardial segments with exercise thallium-201 perfusion defects in patients with myocardial infarction: comparison with late (24-hour) redistribution thallium imaging for detection of reversible ischemia. AB - Exercise thallium-201 24-hour redistribution imaging and myocardial glucose metabolism with F-18-deoxyglucose were used to identify reversible ischemia in 30 patients with previous myocardial infarction. Metabolic images were obtained using a planar gamma camera fitted with a rotating tungsten collimator. Of 184 exercise thallium perfusion defects, late redistribution occurred in 88. Metabolic evidence for reversibility (metabolism-perfusion mismatch) was identified in 91% of these 24-hour reversible segments. However, 72% of the segments with fixed perfusion defects also had residual ischemia by F-18 deoxyglucose. Out of 26 fixed severe thallium defects, 69% had F-18-deoxyglucose evidence for residual ischemia. A subset of 14 patients underwent serial exercise thallium scintigraphy or gated equilibrium radionuclide angiography after revascularization or medical therapy. Out of 46 fixed thallium defects in these patients, 30 demonstrated serial scintigraphic improvement. F-18-deoxyglucose thallium mismatch was present in 81% of these segments, but was absent in the majority of the unimproved segments. Thus quantitative planar imaging of myocardial glucose metabolism with F-18-deoxyglucose using a well-collimated gamma camera can detect clinically important reversible ischemia in segments with fixed thallium defects at late redistribution imaging. PMID- 1636574 TI - Lack of influence of pretreatment antistreptokinase antibody on efficacy in a multicenter patency comparison of intravenous streptokinase and anistreplase in acute myocardial infarction. AB - Antistreptokinase antibodies present in patients as a result of previous streptococcal infections might theoretically influence the thrombolytic response to streptokinase or anistreplase. The potential influence of antibody, measured as antigen binding to immunoglobulin G, was investigated in a randomized, double blind, multicenter patency comparison of intravenous streptokinase (1.5 million units/60 minutes) and intravenous anistreplase (30 units/2 to 5 minutes) in patients with acute myocardial infarction. Antibody results were evaluated in 333 patients (from a total study population of 370 patients) less than 76 years of age with ECG evidence of ST segment elevation who could be treated within 4 hours of the onset of symptoms. Variations in pretreatment circulating levels of antibody did not influence angiographically defined early coronary patency rates (Thrombolysis in Myocardial Infarction grade 2 or 3 perfusion, measured at a mean of 140 minutes after therapy was begun) for either streptokinase or anistreplase. Similarly the lytic response represented by systemic plasminogen activation and measured as changes in plasma plasminogen and fibrinogen levels after dosing (at mean times of 90 minutes and 24 hours) was not correlated with baseline antibody levels. Furthermore, pretreatment antibody was not a risk factor for poor outcome in response to streptokinase or anistreplase (reocclusion within 24 hours, in hospital death, or stroke) and did not correlate with hypotension or allergic type reactions recorded as adverse events. In conclusion, within the population limits defined by the inclusion and exclusion criteria of the study (patients were excluded if they had received streptokinase or anistreplase within the previous 6 months), pretreatment antistreptokinase immunoglobulin G is not a significant determinant of the efficacy response to streptokinase or anistreplase. PMID- 1636575 TI - Plasma plasminogen activator inhibitor activity and tissue plasminogen activator levels in patients with unstable angina and those with coronary spastic angina. AB - Plasminogen activator inhibitor (PAI) activity and tissue plasminogen activator (TPA) antigen were measured in venous samples in 14 patients with unstable angina consisting of eight patients with organic stenosed coronary arteries and six patients with coronary spastic angina (unstable angina group); in 14 patients with stable exertional angina (stable exertional angina group); and in 14 patients with chest pain syndrome (chest pain syndrome group). The plasma levels of PAI activity were higher (p less than 0.01) in the unstable angina group than in the stable exertional angina group and the chest pain syndrome group (12.3 +/- 1.0 versus 5.1 +/- 0.7 and 4.8 +/- 0.6 IU/ml). The plasma levels of TPA antigen were also higher (p less than 0.05) in the unstable angina group than in the stable exertional angina group and the chest pain syndrome group (10.2 +/- 1.3 versus 6.5 +/- 0.8 and 6.0 +/- 0.7 ng/ml). There were no significant differences in PAI activity and TPA antigen levels between the stable exertional angina group and the chest pain syndrome group. Furthermore, both PAI activity and TPA antigen levels in the unstable angina group decreased to the levels in the stable exertional angina group and the chest pain syndrome group after treatment (p less than 0.01). In conclusion, the increased plasma PAI activity in patients with unstable angina and in those with coronary spastic angina indicates that the fibrinolytic system is impaired in these patients. PMID- 1636577 TI - Intracoronary electrocardiogram during coronary angioplasty. AB - This prospective study examines the data derived from the intracoronary electrocardiogram (ECG) (derived from the coronary guide wire) compared with that from four standard surface leads (I, II, III, and V2) in documenting myocardial ischemia during coronary angioplasty. Intracoronary and surface ECGs were simultaneously recorded in 300 consecutive patients (mean age 59 +/- 10; range 33 to 80 years; 246 males [82%] during coronary angioplasty in 368 lesions (167 left anterior descending [46%], 85 left circumflex [23%], 107 right coronary arteries [29%], and nine bypass grafts [2%]), before balloon inflation, at 1 minute of inflation, and at the end of the procedure. ST segment changes (greater than 0.1 mV) were observed in the intracoronary ECG in 306 lesions (83%) (151 left anterior descending [88%], 75 left circumflex [89%], and 80 right coronary arteries [73%]) versus in 245 lesions (67%) in the surface ECG (126 left anterior descending [73%], 43 left circumflex [47%], and 76 right coronary arteries [70%]; [p less than 0.0001]). The mean ST segment shift was 0.5 +/- 0.4 mV in intracoronary and 0.1 +/- 0.2 mV in standard leads (p less than 0.0001). ST elevation was seen in 97% of cases with intracoronary ECG changes versus in 83% with surface ECG changes. The remainder had ST depression. A total of 48 lesions (13%) did not produce ECG changes and 62 (16%) had silent ischemia. In 75 lesions (21%), ECG changes were seen only in the intracoronary ECG, compared with 14 lesions (4%) with changes only in the surface ECG (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636576 TI - Abnormal nondefect zone myocardial thallium washout ratio in patients with reversible thallium defects and normal coronary arteriograms. AB - Thallium myocardial defects in patients with no angiographic coronary artery stenosis have been attributed to attenuation effects and other artifacts. Of 323 patients having thallium myocardial imaging following dipyridamole infusion, 10 of 159 patients with a segmental perfusion abnormality were found to have no luminal diameter stenosis greater than 20% on coronary angiography and no electrocardiographic (ECG) evidence of myocardial infarction or left bundle branch block. A time-standardized regional thallium washout ratio was calculated as thallium myocardial counts with dipyridamole to counts without dipyridamole. In comparison to 10 age-matched control patients with no evidence of cardiac disease and no myocardial thallium defect, study patients had a lower regional myocardial thallium washout ratio from both the defect and nondefect (1.57 +/- 0.40 versus 2.27 +/- 0.92, p = 0.041) zones. Nine of the 10 study patients had independent evidence of noncoronary heart disease, including echocardiographic or ECG evidence of left ventricular hypertrophy in six patients. In patients with thallium defects and normal coronary arteriograms, a time-standardized regional thallium myocardial washout ratio for the nondefect zone may aid in the differentiation of patients with noncoronary heart disease from those with soft tissue artifacts. PMID- 1636578 TI - Efficacy of directional coronary atherectomy in cases unsuitable for percutaneous transluminal coronary angioplasty (PTCA) and after unsuccessful PTCA. AB - Directional coronary atherectomy (DCA) was used in 10 female and 50 male patients with an average age of 58 years. They were categorized into three different groups depending on the indications for atherectomy. Group 1 included all patients who had atherectomy as their primary intervention (n = 20) because they were assumed to be unsuitable for percutaneous transluminal coronary angioplasty (PTCA). Group 2 consisted of patients in whom DCA was used after failed balloon dilatation with unsuccessful but uneventful treatment (n = 17). Group 3 (n = 23) included patients in whom DCA was performed as a "rescue" or "bailout" procedure after unsuccessful PTCA resulting in critical ischemia (ECG changes, chest pain, hypotension, and shock). The target lesions were located in the left main artery in two, left anterior descending artery in 43, right coronary artery in 15, and aortocoronary venous bypass in five. The mean length of the lesions was 8 mm (2 to 25 mm). The overall success rate for 65 lesions was 92%. The mean stenosis was reduced from 87 +/- 12% to 19 +/- 17% in patients with primary success. Presently available follow-up angiograms (30) showed six restenoses. Major complications occurred in seven patients (myocardial infarction in two and coronary artery bypass graft surgery within 24 hours in five); there were no deaths. Our results show that DCA is a safe and effective technique that can extend the use of percutaneous procedures and provide a promising nonsurgical option in cases of unsuccessful PTCA. PMID- 1636579 TI - Catheter ablation of accessory atrioventricular pathways in 114 symptomatic patients with Wolff-Parkinson-White syndrome--a comparative study of direct current and radiofrequency ablation. AB - To evaluate and compare the safety and efficacy of catheter-mediated direct current and radiofrequency ablation in patients with Wolff-Parkinson-White syndrome, 114 patients with accessory pathway-mediated tachyarrhythmias underwent catheter ablation. Electrophysiologic parameters were similar in patients undergoing direct-current (group 1, 52 patients with 53 accessory pathways) and radiofrequency (group 2, 62 patients with 75 accessory pathways) ablation. Immediately after ablation, 50 of 53 accessory pathways (94%) were ablated successfully with direct current, but 2 of the 50 accessory pathways had early return of conduction and required a second ablation; 72 of 75 accessory pathways (96%) were ablated successfully with radiofrequency current. In the three accessory pathways in which radiofrequency ablation was unsuccessful, a later direct-current ablation was successful. During follow-up (group 1, 14 to 27 months; group 2, 8 to 13 months), none of the patients with successful ablation had a recurrence of tachycardia. Complications in direct-current ablation included transient hypotension (two patients), accidental atrioventricular block (one patient), and pulmonary air trapping (two patients); complications in radiofrequency ablation included cardiac tamponade (one patient) and suspicious aortic dissection (one patient). Myocardial injury and proarrhythmic effects were more severe in direct-current ablation. The length of the procedure and the radiation exposure time were significantly shorter in direct-current (3.5 +/- 0.2 hours, 30 +/- 4 minutes) than in radiofrequency (4.1 +/- 0.4 hours, 46 +/- 9 minutes) ablation. Findings in this study confirm the impression that radiofrequency ablation is associated with fewer complications than direct current ablation and radiofrequency ablation with a large-tipped electrode catheter is an effective and relatively safe nonsurgical method for treatment of Wolff-Parkinson-White syndrome. PMID- 1636580 TI - A comparison of standard and high-dose regimens for the initiation of amiodarone therapy. AB - The effects of two regimens for the initiation of amiodarone therapy were compared in 92 patients with inducible sustained ventricular tachycardia (VT) at baseline electrophysiologic testing. Two groups of 46 patients each received a total of 16.8 gm of oral amiodarone before follow-up electrophysiologic testing. Group A (standard dose) received 1200 mg/day for 14 days, and group B (high dose) received 2400 mg/day for 7 days. Amiodarone suppressed the induction of sustained VT in six subjects (13%) in group A versus 10 (22%) in group B (p = NS). In subjects who continued to have inducible VT after amiodarone loading, the mean increase in cycle length of induced VT was similar in group A (delta = 85 +/- 73 msec) and group B (delta = 78 +/- 59 msec). The mean increase in sinus cycle length, AH and HV intervals, paced QRS duration, and ventricular refractory periods was also not significantly different between the two groups. Side effects developed in 10 (22%) patients in group B but were serious only in one, and one patient required a reduction in dosage. Thus compared to the 14-day standard-dose regimen, the 7-day high-dose regimen was well tolerated and had similar effects on VT inducibility and electrophysiologic variables. Its use may significantly shorten the duration of hospitalization in patients with life-threatening inducible VT who are undergoing loading with amiodarone on an inpatient basis. PMID- 1636581 TI - Washout of long-term treatment with flecainide and propafenone in patients with complex ventricular arrhythmias and cardiac disease. Antiarrhythmic Drug Evaluation Group. AB - To assess the spontaneous variability of ventricular arrhythmias after withdrawal of apparently successful antiarrhythmic therapy, we enrolled in a washout protocol 40 patients who had completed a randomized controlled 2-year study of antiarrhythmic drugs (the Antiarrhythmic Drug Evaluation Group [ADEG] study). All of them had heart disease and were first seen with high-grade ventricular arrhythmias (Lown class 4a and 4b) at enrollment. After 2 years all of them had responded to propafenone or flecainide; patients who completed the study on a regimen of amiodarone were not considered for the washout study. A total of 27 patients discontinued flecainide and 13 propafenone. Seven days after withdrawal they underwent 24- or 48-hour ECG testing and were classified as true responders (TR) if the arrhythmias were present at the same level as 2 years previously and false responders (FR) if they were below the ADEG responsiveness level. TR patients had a third 24-hour ECG 7 days later, after rechallenge with the same treatment, and FR patients had a third ECG without drugs. Adherence to the protocol was ascertained by measuring drug plasma concentrations at every 24-hour ECG recording. No differences were found in distribution of heart disease and grade of ventricular arrhythmias between patients in the washout study and the remaining group of the ADEG trial. Twenty-four of 40 patients (60%) were true responders. In 4 of the 17 patients who had a third 24 hour ECG, the responsiveness to the same drug was not confirmed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636582 TI - Correlation of symptoms with occurrence of paroxysmal supraventricular tachycardia or atrial fibrillation: a transtelephonic monitoring study. The Flecainide Supraventricular Tachycardia Study Group. AB - The purpose of this study was to determine whether symptoms recorded at the time of transtelephonic ECG monitoring (TTEM) correlate with attacks of paroxysmal supraventricular tachycardia (PSVT) or paroxysmal atrial fibrillation (PAF). We studied 113 patients with these arrhythmias who made a total of 3319 TTEM calls during their participation in double-blind, placebo-controlled, crossover, multicenter trials of flecainide therapy. Among 49 patients with PSVT, 62.7% of symptomatic calls were associated with ECG-documented PSVT as compared with 6.8% of asymptomatic calls (p less than 0.001). Similarly, among 69 patients with PAF, 69% of symptomatic calls were associated with ECG-documented PAF compared with 10.6% of asymptomatic calls (p less than 0.001). Both in patients with PSVT and PAF, an attack of PSVT or PAF could be documented by ECG in more than 70% of the calls when patients complained of tachycardia, increased sweating, or dyspnea. The sensitivity of a symptomatic call was 91% for PSVT and 89% for PAF, and it was not influenced by flecainide therapy. However, flecainide therapy was associated with a decrease in the positive predictive value of symptomatic TTEM calls and an increase in false positive TTEM transmissions. We conclude that in patients with symptomatic PSVT or PAF, there is a temporal relationship between symptoms and the occurrence of ECG-documented attacks of PSVT or PAF. However, sole reliance should not be placed on the presence or absence of symptoms as a measure of drug failure or efficacy, and it is important to document the cardiac rhythm by TTEM at the time symptoms are recorded. PMID- 1636583 TI - Arterial blood nicotine concentration and coronary vasoconstrictive effect of low nicotine cigarette smoking. AB - Low-nicotine cigarettes have been advertised to the public as less harmful to the cardiovascular system. We studied the effects of smoking two low-nicotine cigarettes on arterial and venous blood nicotine levels, hemodynamics, and coronary vascular tone in 12 patients referred for diagnostic coronary arteriography. All were chronic smokers as evidenced by their elevated baseline arterial and venous cotinine blood levels (139 +/- 30 ng/ml and 155 +/- 34 ng/ml, respectively). High-resolution coronary angiograms were evaluated "blindly" before and after smoking. An electronic caliper was used to measure the diameter of disease-free coronary segments of the left anterior descending and circumflex arteries. Arterial nicotine levels rose from 5 +/- 1 ng/ml at baseline to 37 +/- 7 ng/ml (p less than 0.01) after the first cigarette was smoked and to 45 +/- 8 ng/ml (p less than 0.01) after the second cigarette. Venous nicotine levels rose from 8 +/- 2 ng at baseline to 15 +/- 3 ng/ml (p less than 0.05) after the first cigarette and to 20 +/- 3 ng/ml (p less than 0.01) after the second cigarette. After the first cigarette heart rate increased 8 +/- 2 beats/min (p less than 0.003) and double product 1229 +/- 400 beats/min x mm Hg (p less than 0.02). Compared to baseline values, after the second cigarette heart rate increased 9 +/ 1 beats/min (p less than 0.001) and double product 1767 +/- 486 beats/min x mm Hg (p less than 0.01). Systolic, diastolic, and mean blood pressure did not change significantly after either the first or second cigarette.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636584 TI - Discordance between responses of contrast echo intensity to increased flow rate in human coronary circulation and in vitro. AB - According to the Stewart-Hamilton equation flow is inversely related to the area under the time-concentration curve produced by the transit of a detectable indicator. To verify the applicability of this principle for contrast echocardiography, we bolus injected a saccharide echo contrast agent (0.8 ml) into an in vitro circulatory model at variable flow rates. Two-dimensional echo images were digitized, and curves demonstrating the ratio of videointensity over time were derived. As expected, flow was inversely related to the area under the curves (r = 0.93). To apply this principle to human coronary circulation, we bolus injected sonicated iopamidol (4 ml) into the normal left coronary artery of six patients at baseline and after intravenous administration of dipyridamole (0.84 mg/kg in 10 minutes). Echo images were digitized, and myocardial time intensity curves were derived. The area under the curve after dipyridamole administration (210 +/- 128 gray level.sec) did not appear significantly different from that at baseline (177 +/- 80 gray level.sec). Thus a mismatch exists between contrast echo data obtained in vitro and in human coronary circulation. PMID- 1636585 TI - Pregnancy in patients with prosthetic heart valves: the effects of anticoagulation on mother, fetus, and neonate. AB - Maternal and fetal complications in a consecutive series of 60 pregnancies in 49 patients with prosthetic heart valves were prospectively evaluated. Group 1 consisted of 40 pregnancies in 31 patients who were taking oral anticoagulants. No oral anticoagulation was used in 20 pregnancies in 19 patients (group 2). In group 1 there were three instances of acute valvular thrombosis during the 35 pregnancies in patients with mechanical prostheses, with two maternal deaths. There were two episodes of cerebral embolism, one in group 1 and one in group 2. Patients with isolated aortic valve replacement had fewer maternal complications (2 of 13) than patients with isolated mitral valve replacement (15 of 42) without statistical significance. Severe bioprosthesis dysfunction occurred in 4 of 25 pregnancies (one rupture and three stenosis) with two maternal deaths, one in the puerperium and the other in the postoperative period of cardiac surgery during pregnancy. When analyzing obstetric events we observed seven spontaneous abortions and one hydatidiform mole. All spontaneous abortions occurred in group 1. The incidences of prematurity and low birth weight were significantly higher in group 1 than in group 2 (46.6% vs 10.5%, p less than 0.05, and 50% vs 10.5%, p less than 0.05, respectively). Moreover, there was a significant association between prematurity and the mother's New York Heart Association functional class (61.5% in classes III and IV vs 22.2% in classes I and II, p less than 0.05). There were five neonatal deaths, all in group 1 (p = NS vs group 2). Three infants had warfarin-related congenital defects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636586 TI - Heredity and hypertension: impact on metabolic characteristics. AB - This study was performed to evaluate the possible role of heredity in the clinical characteristics of hypertension. Metabolic, endocrine, and renal measurements were compared in subjects with normal blood pressure who had a family history of hypertension (n = 60) with those of subjects with normal blood pressure who did not have a family history of hypertension (n = 48). The groups were matched for age (mean, 44 +/- 2 years and 45 +/- 2 years) and blood pressure (127 +/- 1/77 +/- 1 mm Hg and 127 +/- 2/77 +/- 1 mm Hg). The following parameters were higher in the patients with a family history of hypertension than in those without. Plasma insulin concentrations (14.1 +/- 1.1 vs 10.8 +/- 1.0 microU/ml; p less than 0.05), insulin-glucose ratio (0.15 +/- 0.01 vs 0.11 +/- 0.010; p less than 0.05), norepinephrine concentrations (315 +/- 24 pg/ml vs 208 +/- 20 pg/ml; p less than 0.01), plasma renin activity (2.1 +/- 0.2 ng Angl/ml/hr vs 1.6 +/- 0.2 ng Angl/ml/hr; p less than 0.02), total cholesterol levels (217 +/- 8 mg/dl vs 197 +/- 0.3 mg/dl; p less than 0.05), creatinine clearance (125 +/- 9 ml/min vs 96 +/- 8 ml/min; p less than 0.01), and albumin excretion rate (3.2 +/- 0.3 micrograms/min vs 2.6 +/- 0.3 micrograms/min; p = 0.1). Moreover, patients with a family history of hypertension had smaller increases in systolic blood pressure during treadmill exercise (55 +/- 3 mm Hg vs 64 +/- 3 mm Hg; p less than 0.03). There were no differences in echocardiographic left ventricular mass index between the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636587 TI - Assessment of reperfusion after thrombolytic therapy for myocardial infarction. AB - The benefits of thrombolytic therapy in reducing the mortality associated with acute myocardial infarction are well documented. Presumably, this is on the basis of a patent IRA, although other mechanisms may be involved. Because there is a 25% to 30% failure rate for thrombolytic therapy that is associated with a significantly worse prognosis, it is crucial to document reperfusion in a timely fashion. In cases of failure to reperfuse, the patient could be considered a candidate for secondary mechanical intervention. While coronary arteriography is presently the "gold standard" to document reperfusion, this is an invasive procedure associated with small but defined risks for the patient. A noninvasive marker that is readily available and highly accurate is most desirable. There are a number of methods currently used to document coronary reperfusion noninvasively. This review discusses the advantages and disadvantages of each method, and the need for continued evaluation and refinement in noninvasive modalities to identify patients who are candidates for further intervention. PMID- 1636588 TI - Advantages and limitations of methods to detect, localize, and quantitate intracardiac left-to-right shunting. PMID- 1636589 TI - Electrocardiography of myocarditis revisited: clinical and prognostic significance of electrocardiographic changes. AB - To clarify the clinical and prognostic value of the ECG, an ECG review was undertaken in 45 consecutive patients with a histologic diagnosis of active myocarditis (29 men and boys and 16 women and girls; age, 36.8 +/- 15 years; idiopathic myocarditis, 39 cases). In patients (21) with symptoms of recent onset (less than or equal to 1 month) AV block and repolarization abnormalities were the prevailing ECG features at the time of admission, and a pseudoinfarction pattern (Q waves plus ST-segment elevation) frequently heralded a rapidly fatal course ("fulminant myocarditis"). Left atrial enlargement and atrial fibrillation, left ventricular hypertrophy and LBBB, which prevailed in patients who had symptoms for longer periods, corresponded to the most severe degree of left ventricular dysfunction during the initial hemodynamic and echocardiographic evaluation. The overall mortality rate after 58 +/- 24 months from the time of diagnosis was 29%. Abnormal QRS complexes and LBBB were markers of poor survival, independently of initial indexes of left and right ventricular function, both of which indicate an increased propensity for sudden cardiac death. PMID- 1636590 TI - New developments in pharmacologic stress imaging. AB - The clinical usefulness of cardiac imaging modalities that rely upon the detection of perfusion defects and wall motion disturbances requires conditions that provoke a heterogeneity of coronary flow and a myocardial oxygen imbalance, respectively. Traditionally, this has been achieved by exercise stress testing. Many patients cannot perform dynamic exercise sufficiently for various reasons. Pharmacologic stress has been proven to be an attractive alternative for physical exercise. Currently, several stressing agents are used in conjunction with thallium-201 scintigraphy, 2-D echocardiography and, recently, MRI. The most employed agents include vasodilators, such as dipyridamole and adenosine, and catecholamines, such as dobutamine (Table VI). The predominant rationale of thallium-201 perfusion scintigraphy is based on the creation of a flow maldistribution between territories supplied by normal arteries and those supplied by stenotic arteries that does not necessarily require ischemia. Dipyridamole and adenosine, as rather selective coronary vasodilators, are well suited to provoke such a condition and may be classified as the ideal markers of myocardial perfusion. 2-D echocardiography and MRI have the potential to provide noninvasively derived information of cardiac dynamics and regional myocardial function. To assess the functional significance of coronary artery disease, detection of wall motion abnormalities and alterations in ejection fraction require the presence of myocardial ischemia. Dobutamine, as a widely applied inotropic agent in the management of severely depressed left ventricular contractile function, seems to be an appropriate pharmacologic stressor when heart failure is absent. By increasing contractility, heart rate, and systolic arterial pressure, it is capable of inducing an imbalance between myocardial oxygen demand and supply, leading to ischemia in patients with coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636591 TI - The pathologic changes in the conduction system beyond the age of ninety. AB - The conduction systems of two women who were 92 and 91 years of age, respectively, were examined by serial section. The first patient had sick sinus syndrome for more than 20 years, and the second patient had intermittent complete AV block that alternated with normal sinus rhythm for 12 years before her death. Both patients had severe coronary artery disease and had pacemakers and were doing well. The conduction systems in both revealed fatty metamorphosis in the approaches to the SA and AV nodes, the SA node, the AV node, and the atria with fibrotic changes in the ventricular septum, the AV bundle, and the bundle branches. Patient 1 had normal SA nodal artery and patient 2 had extensive vascularization of the AV node. As the heart ages, fatty replacement of the atria affect the SA and AV nodes, and fibrotic changes of the ventricular septum affect the AV bundle and the bundle branches. Adequate collateral anastomosis to the conduction system may prevent the development of permanent complete AV block in the elderly. PMID- 1636592 TI - Biventricular apical rupture and formation of pseudoaneurysm: unique flow patterns by Doppler and color flow imaging. PMID- 1636593 TI - Unsuspected third coronary artery in a candidate for coronary bypass surgery. PMID- 1636594 TI - Ventricular tachycardia in a patient with congenital coronary arteriovenous fistula. PMID- 1636595 TI - Vasospastic angina in Crow-Fukase syndrome. PMID- 1636596 TI - Myocardial infarction associated with anabolic steroid use in a previously healthy 37-year-old weight lifter. PMID- 1636597 TI - Acute arteritis after coronary angioplasty. PMID- 1636598 TI - Fibrinolytic therapy for superior vena cava and right atrial thrombosis: diagnosis and follow-up with biplane transesophageal echocardiography. PMID- 1636599 TI - Transesophageal echocardiographic evaluation of intracardiac lymphoma. PMID- 1636600 TI - Myocardial entrapment by lymphoma: a cause of reversible segmental left ventricular dysfunction. PMID- 1636601 TI - Spontaneous contrast echoes in pericardial effusion: sign of gas-producing infection. PMID- 1636602 TI - Posterior mediastinal masses: rare causes of cardiac compression. PMID- 1636603 TI - Variation in Doppler-derived stenotic aortic valve area during ejection. PMID- 1636604 TI - Heart transplant in Ebstein's anomaly with endocardial fibroelastosis. PMID- 1636605 TI - Verapamil-induced gingival hyperplasia in children. PMID- 1636606 TI - Aortic dissection following intraaortic balloon insertion: recognition by transesophageal echocardiography. PMID- 1636607 TI - The diagnostic value of imaging techniques for aortic dissection. AB - Previous studies conducted in high-risk populations have reported high predictive values and accuracies for diagnostic imaging techniques for aortic dissection. To see how these techniques perform in low-risk populations, we used Bayes' theorem to calculate predictive values and accuracies for angiography, CT, MRI, and TEE. In high-risk populations (disease prevalence = 50%), positive predictive values were all greater than 85%. In intermediate risk populations (disease prevalence = 10%), positive predictive values were greater than or equal to 90% for CT, MRI, and TEE, but were 65% for angiography. In low-risk populations (disease prevalence = 1%), positive predictive values were 100% for MRI and less than or equal to 50% for angiography, CT, and TEE. In all three populations, negative predictive values and accuracies were greater than or equal to 85%. From these results we conclude that diagnostic imaging techniques for aortic dissection do not perform as well in low-risk populations as they do in high-risk populations. PMID- 1636608 TI - Magnesium deficiency and sudden death. AB - A link between Mg deficiency and sudden death is suggested by a substantial number of studies published over the past three decades. Data come from epidemiologic, autopsy, clinical, and animal studies. They suggest that: (1) Sudden death is common in areas where community water supplies are Mg-deficient. (2) Myocardial Mg content is low in people who die of sudden death. (3) Cardiac arrhythmias and coronary artery vasospasm can be caused by Mg deficiency and (4) Intravenous Mg reduces the risk of arrhythmia and death immediately after acute myocardial infarction. Because of these data, Mg supplementation has been proposed as a possible method of reducing the risk of sudden death. Suggested ways of supplementing Mg include public education to change dietary habits, addition of Mg to community water supplies, fortification of foods, and oral supplementation. Despite the substantial number of studies linking Mg deficiency with sudden death, no prospective studies have yet investigated whether large scale Mg supplementation is useful for the primary prevention of sudden death. PMID- 1636609 TI - Regional changes in body composition by time of year in healthy postmenopausal women. AB - We examined regional changes in fat, lean, and bone tissue for greater than 1 y in 125 postmenopausal women. Duplicate whole-body scans were performed at 6-mo intervals. Period 1 was June or July to December or January and period 2 was December or January to the following June or July. Lean and bone tissue mass in the arms, legs, trunk, and whole body increased in period 1 and decreased in period 2 [eg, lean tissue in legs increased 1.84 +/- 0.41% (mean +/- SE) in period 1 and decreased 2.84 +/- 0.39% in period 2, P less than 0.001]. In each region except the arms, fat tissue decreased in period 1 and increased in period 2. Quadriceps muscle strength was correlated with lean tissue mass of the legs [rp (controlled for height) = 0.24, P V 0.02] and physical activity was correlated with quadriceps strength. Overall, body weight did not change significantly (0.17 +/- 0.41% increase, P greater than 0.20); however, there was a net loss of 1.08 +/- 0.39% (P less than 0.01) in lean tissue in the legs and a net increase of 3.43 +/- 1.12% (P less than 0.01) in fat tissue in the trunk. PMID- 1636610 TI - Effects of dietary protein deficiency on mineral metabolism and bone mineral density. AB - The effects of dietary protein restriction on mineral and bone metabolism are uncharacterized. We studied growing rats fed a diet low in protein (5%) for 4, 6, and 8 wks (n = 10 animals/group) and compared them with animals pair-fed with a protein-replete (18%) diet. The low-protein diet rapidly induced a profound hypocalciuria that persisted for greater than or equal to 8 wk. Serum calcium and phosphorus concentrations were not affected but serum total and free 25 dihydroxyvitamin D concentrations as well as gastrointestinal calcium absorption were lower in the low-protein animals. Skeletal dimensions were reduced in the protein-deprived rats but there were no significant differences in bone mineral content between control and low-protein animals at 4, 6, and 8 wks. Hence, dietary protein deprivation resulted in slower growth but bone mineral density was maintained when there was a marked reduction in urinary calcium excretion. PMID- 1636611 TI - Impact of diabetic status, dietary intake, physical activity, and smoking status on body mass index in NHANES II. AB - Individuals with non-insulin-dependent diabetes mellitus (NIDDM) have a higher body mass index (BMI) than nondiabetic individuals and it has been reported that individuals with NIDDM have more difficulty losing excess weight. To assess an independent effect of NIDDM on weight status, analyses were conducted to predict BMI with variables previously associated with weight status. Subjects from the Second National Health and Nutrition Examination Survey were categorized into three groups: individuals with NIDDM and on oral medication, individuals with diet-controlled NIDDM, and nondiabetic adults. Additionally, planned orthogonal comparisons between these groups were conducted after other predictors were controlled for; 9.18% of the variability was explained for men (P less than 0.001) whereas 12.11% was explained for women (P less than 0.0001), with several variables significantly related in each model. An independent effect for diabetes status was found in both sexes and there were no differences in BMI between NIDDM groups in either sex. PMID- 1636612 TI - Total energy expenditure of healthy Swedish women during pregnancy and lactation. AB - Total energy expenditure (TEE) was estimated in healthy Swedish women by the doubly labeled water method in a longitudinal study during pregnancy and lactation. Measurements were made before pregnancy (A); in gestational weeks 16 18 (B), 30 (C), and 36 (D); as well as 2 (F) and 6 (G) mo after delivery. When the results were interpreted, earlier published data regarding resting metabolic rate (RMR), energy intake, and energy in breast milk were also considered. TEE (MJ/d) and TEE/RMR were 10.5 +/- 2.2 (mean +/- SD) and 1.87 +/- 0.42 (n = 28), 9.6 +/- 2.8 and 1.65 +/- 0.67 (n = 22), 12.5 +/- 3.4 and 1.82 +/- 0.45 (n = 22), 12.2 +/- 4.1 and 1.66 +/- 0.52 (n = 19), 10.6 +/- 2.0 and 1.82 +/- 0.41 (n = 23), and 10.8 +/- 2.7 and 1.79 +/- 0.42 (n = 23) at A, B, C, D, F, and G, respectively. The results indicated that physical activity tended to be decreased during early pregnancy. Taking changes in body energy stores into consideration, it was estimated that subjects recorded 86% and 77% of their energy intakes at A and F respectively. PMID- 1636613 TI - Daily energy expenditure in free-living children: comparison of heart-rate monitoring with the doubly labeled water (2H2(18)O) method. AB - Total energy expenditure (TEE) was measured simultaneously in 36 free-living children aged 7, 9, 12, and 15 y over 10-15 d by the doubly labeled water (DLW) method and for 2-3 separate days by heart-rate (HR) monitoring. The 95% confidence limits of agreement (mean difference +/- 2SD) were -1.99 to +1.44 MJ/d. HR TEE discrepancies ranged from -16.7% to +18.8% with 23 values lying within +/- 10% of DLW TEE estimates. Boys and girls spent 462 +/- 108 and 318 +/- 120 min/d, respectively, in total physical activity (P less than 0.01). Time spent in moderate and vigorous physical activity (MVPA) was 68 +/- 37 min/d by younger children (7-9 y) and 34 +/- 24 min/d by older children (12-15 y) (P less than 0.001). Younger boys engaged in MVPA (91 +/- 33 min/d) and vigorous physical activity (VPA) (35 +/- 15 min/d) significantly longer than younger girls (MVPA, 39 +/- 16 min/d, P less than 0.001; VPA, 10 +/- 4 min/d, P less than 0.01) as did older boys (MVPA, 52 +/- 21 min/d; VPA, 30 +/- 18 min/d) compared with older girls (MVPA, 15 +/- 10 min/d; VPA, 8 +/- 5 min/d). HR monitoring provides a close estimation of the TEE of population groups and objective assessment of associated patterns of physical activity. PMID- 1636614 TI - The interactive effects of dietary quality on the growth and attained size of young Mexican children. AB - Predictors of attained size at 30 mo and growth rate between 18 and 30 mo (eg, diet, maternal size, morbidity, age at weaning, and selected environmental factors) were investigated by using longitudinal data from 67 Mexican children aged 18-30 mo. These children were small because of growth stunting in early infancy. Between 18 and 30 mo they grew on average at the 50th percentile of National Center for Health Statistics references values for weight, and the 25th for length. Size at 30 mo and growth rates were unrelated to energy or protein intakes during the previous year, but positively related to consumption of animal origin foods. Maternal weight predicted size and growth only for children with larger intakes of animal products. Individual rates of weight and length growth were uncorrelated on average, correlated negatively when animal-product intake was low, and positively only when more animal products were consumed. Integrated weight and length growth, and the influence of maternal size on growth, may be disrupted by poor dietary quality. Different children would be identified as malnourished depending on whether weight or length growth was measured. PMID- 1636615 TI - Maternal serum folate and zinc concentrations and their relationships to pregnancy outcome. AB - To evaluate the relationship between folate and zinc, and its effect on pregnancy outcome, maternal serum folate and zinc concentrations were determined at 18 and 30 wk gestation in a defined population of 285 pregnant women as part of a large scale study to identify risk factors for fetal growth retardation (FGR). These results were correlated with birth weight and Apgar scores of newborn infants and with maternal infections during the perinatal period. A weak linear relationship was observed between maternal serum folate and zinc concentrations at 30 wk gestation. Folic acid supplementation had favorable effects on birth weight and Apgar scores of newborns, and reduced prevalence of FGR and maternal infections. No significant correlation was found between serum zinc concentration and birth weight of infants. The concept that folic acid supplementation has an adverse effect on maternal zinc nutriture and pregnancy outcome was not supported. PMID- 1636616 TI - Polyamines in human and rat milk and in infant formulas. AB - Polyamines are ubiquitous compounds known to be involved in cell proliferation and differentiation in many tissues. Enteral administration of these compounds has been shown to produce effects in suckling and adult animals. Using HPLC techniques, we verified the presence of putrescine, spermidine, and spermine in human milk and quantitated their concentration in samples collected from the first week up to 4 mo of lactation. Mean values of these compounds ranged (per liter) from 0 to 615 nmol putrescine, from 73 to 3512 nmol spermidine, and from 722 to 4458 nmol spermine. Polyamine concentrations in infant formulas were dependent on the protein source, the particular polyamine, and the protein concentration of the formula. Concentrations of these three compounds in rat milk over the first 3 wk of lactation were higher than in human milk, with spermidine being the polyamine most elevated compared with human milk (almost 20-fold higher). An artificial formula used for the rearing of suckling rats contained trace to immeasurable amounts of polyamines. Our study identifies milk as one vehicle for polyamine delivery to the intestinal mucosa of suckling animals. PMID- 1636617 TI - Effects of diets rich in monounsaturated fatty acids on plasma lipoproteins--the Jerusalem Nutrition Study. II. Monounsaturated fatty acids vs carbohydrates. AB - Seventeen male Yeshiva students were randomly allocated to a crossover study with two 12-wk dietary periods of monounsaturated fatty acids (MUFAs) vs a carbohydrate (CHO)-rich diet while concentrations of saturated (SFAs) and polyunsaturated (PUFAs) fatty acids were kept similar. Total plasma cholesterol (TC) decreased significantly by approximately 7.7% and low-density-lipoprotein cholesterol (LDL-C) by 14.4% on the MUFA diet, whereas on the CHO diet no significant change in cholesterol concentrations occurred, in contrast to that predicted by the equations of Keys and Hegsted. Concentrations of high-density lipoprotein cholesterol (HDL-C) did not change significantly on either diet. On the MUFA diet there was a significantly lower proneness to peroxidation of plasma and LDL lipids and less extensive metabolism of conditioned LDL by peritoneal macrophages. We conclude that dietary MUFAs lower TC and LDL-C concentrations, independently of other dietary fatty acids and in addition may reduce the susceptibility of LDL to oxidative stress. PMID- 1636618 TI - Lipoprotein-containing apolipoprotein A-I: sex-related quantitative and qualitative changes in this lipoprotein subspecies after ingestion of fat. AB - We investigated the postprandial changes of two species of lipoproteins containing apolipoprotein (apo)A-I: lipoprotein containing apo A-I but no apo A II (LpA-I), and lipoprotein containing apo A-I and apo A-II (LpA-I/A-II). These lipoproteins were isolated from 10 men and 11 women at 0, 4, and 6 h after they had eaten butter. In LpA-I, the concentrations of all lipids except triglyceride were increased at 4 and 6 h in the women. In the men all lipids were increased only at 4 h. The increase of apo A-I concentration was found at 6 h only in the women. In LpA-I/A-II, the concentrations of all lipids were increased at 4 h and only phospholipid (PL) was increased at 6 h in the women. In the men, free cholesterol and PL were increased at 4 and 6 h. The increases of apo A-I and apo A-II concentrations were found at 4 and 6 h only in the men. These results suggest that the postprandial changes are sex-related and may relate to the different incidence of atherosclerotic cardiovascular disorders. PMID- 1636619 TI - Gastroileal nitrogen and electrolyte movements after bovine milk ingestion in humans. AB - Gastric emptying and flow rates of nitrogen and electrolytes (Na+, K+, Cl-, Mg2+, Ca2+) were studied in humans after bovine milk ingestion. With water as the control, intestinal effluents were collected after meal ingestion at the beginning of the jejunum or in the distal ileum. The flow rate of the effluent peaked in the first 40-min period after meal ingestion and returned to the initial amount within 100 min. After water ingestion the quantity of nitrogen recovered in the digesta remained unchanged both in the jejunum and in the ileum during the test period. After milk ingestion the nitrogen concentration in the jejunal digesta peaked in the first 20 min. Forty-two percent of milk nitrogen was absorbed before the jejunum and 93% was absorbed before the end of the ileum. These results showed that for the completion of the absorption of dietary proteins such as milk proteins, the lower part of the intestine is necessary. PMID- 1636620 TI - A method for determining concentrations of retinol, tocopherol, and five carotenoids in human plasma and tissue samples. AB - To explore the relation between plasma and tissue concentrations of seven fat soluble micronutrients (retinol, alpha-tocopherol, lutein, cryptoxanthin, lycopene, alpha-carotene, and beta-carotene), we developed methods for clarifying plasma and tissue samples and quantitating these seven analytes simultaneously by using HPLC with ultraviolet detection. Clarification of tissue samples was performed by using enzymatic digestion followed by mechanical homogenization; saponification was avoided and tocopherol nicotinate was used as an internal standard. Precision and sensitivity for small samples of plasma and solid tissues were determined. Accuracy for plasma samples was assessed by comparing results obtained by using this method with those obtained by using older, standardized methods. Results from application of this method to patient samples of plasma and various tissues are presented. This method will be of interest to investigators seeking to quantitate these seven micronutrients in solid tissue samples, but desiring to avoid the usual saponification step required in most other reported techniques. PMID- 1636621 TI - Distribution of biotin in human plasma: most of the biotin is not bound to protein. AB - Estimates of the plasma concentration of biotin differ considerably. Variation in detectability of biotin bound covalently to protein is one potential source of disagreement. In this study we determined the amount of biotin covalently bound to plasma protein. First, greater than 99% of free and reversibly bound biotin was removed by dialysis; then greater than 90% of covalently bound biotin was released by acid hydrolysis. For plasma samples from 11 normal adults, the ratio of covalently bound biotin to free biotin was 0.15 +/- 0.09 (mean +/- SD). Taking into account the additional biotin that is reversibly bound to protein, this study provides evidence that approximately 12% of total biotin in plasma is covalently bound, 7% is reversibly bound, and 81% is free. We conclude that covalently bound biotin cannot account for the reported sixfold increase in biotin detected after acid hydrolysis. We speculate that the reported increase was an artifact caused by substances produced during acid hydrolysis of plasma. PMID- 1636622 TI - Metabolism of carotenoid analogs in humans. AB - Single oral doses (100 mumol) in peanut oil of 4,4'-dimethoxy-beta-carotene, ethyl beta-apo-8'-carotenoate, and beta-apo-8'-carotenal were administered to healthy adult male subjects (n = 4-6). Blood samples were taken frequently thereafter, and serum carotenoids and retinoids were analyzed by HPLC. The metabolism of the three analogs was very different; 4,4'-dimethoxy-beta-carotene was oxidized at the 4 and 4' positions but apparently not cleaved, whereas ethyl beta-apo-8'-carotenoate was not detectably metabolized, and beta-apo-8'-carotenal was extensively converted to its corresponding acid, alcohol, and fatty acyl ester and detectably converted to retinyl ester and possibly to two shorter beta apocarotenals. Serum concentrations of endogenous retinoids and carotenoids, except as noted above, were not affected in any case. Kinetically, the maximum serum concentrations, areas under the curve, and mean sojourn times for the three analogs differed by 50-, 270-, and 5-fold, respectively. For any given analog, however, the fractional standard deviations for these parameters were only 0.2 0.5. PMID- 1636623 TI - Serum copper and zinc in random samples of the population of Northern Ireland. AB - Serum copper and zinc concentrations (mumol/L) were measured in nonfasting subjects aged 25-64 y participating in two independent population surveys in Northern Ireland. In 1983-84, copper in 1144 males was 17.2 +/- 3.1 (mean +/- SD) and zinc was 12.1 +/- 1.7 (SD). Copper in 1055 females, neither pregnant nor taking estrogens or progestogens, was 19.0 +/- 3.9 and zinc was 11.6 +/- 1.4. In 1986-87 copper in 1142 males was 17.9 +/- 3.3 and zinc was 13.2 +/- 2.1. Copper in 1034 females was 20.1 +/- 3.9 and zinc was 12.7 +/- 2.0. Zinc but not copper concentrations decreased from early morning to late afternoon; both were unaffected by reported postprandial time. There was a positive relationship between copper and age for both sexes but zinc showed only a slight upward trend with age. A positive relationship between copper and the aggregation of classical risk factors for coronary heart disease was demonstrated. PMID- 1636624 TI - Effect of glyburide and omega 3 fatty acid dietary supplements on glucose and lipid metabolism in patients with non-insulin-dependent diabetes mellitus. AB - Using a random crossover design, we examined the effects of glyburide for 4 wk on glucose, insulin, lipid, and lipoprotein metabolism in 10 men with non-insulin dependent diabetes (NIDDM) receiving dietary fish-oil concentrates containing omega 3 (n-3) fatty acids (8 g/d). Compared with glyburide alone, fasting plasma glucose concentrations increased with fish oil. Although glyburide with fish oil decreased fasting glucose concentrations, they did not return to baseline. Basal insulin concentrations were unaltered by fish oil without or with glyburide; however, postprandial insulin concentrations were decreased by fish oil. Although total cholesterol and triglyceride concentrations were unchanged, very-low density-lipoprotein cholesterol concentrations decreased and low-density lipoprotein cholesterol rose and apolipoprotein B concentrations trended higher. Thus, glyburide only partially rectified the impaired fuel homeostasis associated with fish-oil supplements in patients with NIDDM. Therefore, we do not recommend intake of fish oil concentrates containing n-3 fatty acids in patients with NIDDM. PMID- 1636625 TI - Fat mass in predicting resting metabolic rate. PMID- 1636626 TI - Previously undescribed disk-capsule innervation: some speculative thoughts for TMD clinicians. PMID- 1636627 TI - The holodent system, a new technique for measurement and storage of dental casts. AB - A system for producing holograms and for three-dimensional measuring on holograms is described. The precision of the system was evaluated when three-dimensional measurements were made on (1) a holographic image superimposed on the corresponding object and (2) two superimposed holographic images of the same object. When a metal test object with sharp well-defined contours, easy to reorientate was used, the precision was 0.02 to 0.11 mm for x, y, and z coordinates (transverse, longitudinal, and vertical planes). When dental casts that have less distinct contours were used, precision was reduced to 0.03 to 0.43 mm. Precision was high for the x and y coordinates and satisfactory for the z coordinate. The system has a precision that is equal to that of previously reported methods and may be well-suited for studies of dental positional changes in longitudinal materials of study models. Holograms of dental casts may solve storage problems by replacing space consuming plaster models. PMID- 1636628 TI - Load-deflection characteristics of nickel-titanium alloy wires after clinical recycling and dry heat sterilization. AB - The desirable mechanical properties of nickel-titanium alloy wires and their relatively high cost has prompted many clinicians to recycle these wires. Clinical recycling exposes the wires to several weeks or months of mechanical stresses and elements of the oral environment, as well as sterilization between uses. In a previous study it was noted that clinical recycling combined with cold sterilization alters the load-deflection characteristics and surface topography of nickel-titanium wires. Whether similar changes in mechanical properties occur in wires subjected to repeated clinical use and dry heat sterilization is not yet clear. The purpose of this investigation was to determine the effects of in vivo recycling interposed by dry heat sterilization (together referred to as clinical recycling, CR) on the load-deflection characteristics of nickel-titanium alloy wires. To differentiate the effects of dry heat sterilization (DHS) from those of CR on the behavior of these wires, a series of wires were also subjected to DHS only. Two types of nickel-titanium wires, namely Nitinol and NiTi were subjected to a three-point bending test in an as-received condition (T0), after one cycle (T1), and two cycles (T2) of DHS or CR. Ten wires comprised each subsample. Statistical analyses were done by one-factor repeated measures analysis of variance and Scheffe F test. Both DHS alone, as well as CR, produced significant changes in the loading and unloading characteristics of Nitinol and NiTi wires. However, the changes in the load-deflection characteristics of these wires after DHS only were relatively small, and the clinical significance of these changes is open to question.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636629 TI - Force degradation of closed coil springs: an in vitro evaluation. AB - This in vitro study was designed to determine the force degradation of closed coil springs made of stainless steel (SS), cobalt-chromium-nickel (Co-Cr-Ni) and nickel-titanium (Niti) alloys, when they were extended to generate an initial force value in the range of 150 to 160 gm. The specimens were divided into two groups. Group I included SS, Co-Cr-Ni, and two nickel-titanium spring types (Niti 1 and Niti 2), 0.010 x 0.030 inch with an initial length of 12 mm. Group II was comprised of SS, Co-Cr-Ni, and Niti 3 0.010 x 0.036-inch springs, with an initial length of 6 mm. A universal testing machine was used to measure force. A pilot study determined the extension required for each spring type, so that the initial force was in the range of 150 to 160 gm. Initial force was recorded, and then the springs were extended to the respective distances at 4 hours, 24 hours, 3 days, 7 days, 14 days, 21 days, and 28 days resulting in a total of eight time periods. Between the time intervals, all springs were extended to the same initial extension on specially designed racks and stored in a salivary substitute at 37 degrees C. Means and standard deviations of force values, percent force loss, and mean extension were statistically analyzed. All springs showed a force loss over time. Of the total, the major force loss for most springs was found to occur in the first 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636630 TI - Mandibular remodeling measured on cephalograms. 1. Osseous changes relative to superimposition on metallic implants. AB - We report the results of a study aimed at quantifying remodeling of mandibular surfaces in a sample of growing children who represent those usually treated by orthodontists in the mixed and early adult dentition. The sample, 31 patients with metallic implants of the Bjork-type, was monitored at annual intervals between 8 1/2 and 15 1/2 years of age. (Maxillary remodeling changes for the sample have been reported earlier.) The present article reports findings concerning changes at condyle, gonion, menton, pogonion, and point B as identified on lateral cephalograms. Data are reported in the Frankfort plane frame of reference with the cephalograms from different time points superimposed on the metallic implants. Mean displacement at condyle was larger than that at any other landmark and was similar in magnitude and direction to the observations of Bjork when the difference in orientation of the vertical axis in the two studies is taken into account. The mean displacement of gonion was in an upward and backward direction at an angle of approximately 45 degrees to the Frankfort plane. Mean displacements at menton and pogonion were in a downward and backward direction but were very small. Mean displacement at point B was somewhat greater than that of menton and gonion, oriented in an upward and backward direction. Individual variation for most of the parameters measured was sufficiently large to warrant the inference that caution should be used when mean values are applied to the analysis of individual cases. PMID- 1636631 TI - The study of the maxillary sinus areas in different orthodontic malocclusions. AB - In the present study, the maxillary sinus areas have been investigated on orthopantomographs of 103 male and 86 female subjects either with ideal occlusions or with malocclusions. It has been found that malocclusions and sex factors have no effect on the size of the maxillary sinuses, and that sex is a significant factor only in Angle Class II malocclusions. The female subjects with Angle Class II malocclusions have larger maxillary sinuses than the male subjects and the other groups of female subjects. PMID- 1636632 TI - Mandibular growth estimated by four cephalometric measurements. AB - Mandibular growth was estimated by four cephalometric measurements on three lateral cephalograms of 21 subjects. The estimates made by three standard cephalometric approaches were compared with that made by a "scientific" method. The scientific method was based on the change in position of the cephalometric landmark condylion on cephalograms orientated on two metal implants inserted in the mandible. The other three investigated "standard" cephalometric methods were each based on estimating the difference in length between two cephalometric landmarks: (1) pogonion-condylion, (2) pogonion-articulare, and (3) maximum mandibular length. In general, the individual estimates of the amount of mandibular growth by the scientific method and that estimated by each of the standard cephalometric methods were not proportional. Some factors affected the estimates of mandibular growth. For example, (1) the growth direction of the condyle, (2) the change in position of pogonion on the mandible during the growth, and (3) the apposition of bone on the chin in some cases. The amount of mandibular growth, which is estimated by the standard cephalometric methods, and growth velocity curves, which is based on such estimates, are therefore not valid. Accordingly, conventional cephalometric analyses are not as reliable at traditionally envisaged. PMID- 1636633 TI - The effect of clinical use and sterilization on selected orthodontic arch wires. AB - The effect of clinical use and various sterilization/disinfection protocols on three types of nickel-titanium, and one type each of beta-titanium and stainless steel arch wire was evaluated. The sterilization/disinfection procedures included disinfection alone or in concert with steam autoclave, dry heat, or cold solution sterilization. No clinically significant differences were found between new and used arch wires. The direction of load application to the arch wire and the particular segment of arch wire tested was found to cause substantial differences in generated loads for certain arch wire types. PMID- 1636634 TI - Anterior crossbite correction in the early deciduous dentition. PMID- 1636635 TI - Chaos theory and fractals. PMID- 1636636 TI - Facial height index. AB - The ratio of posterior facial height to anterior facial height, called the facial height index, is described. The clinical uses of the facial height index are discussed. One of its uses is illustrated in the accompanying case report. PMID- 1636637 TI - Reconditioning and reuse of orthodontic devices. PMID- 1636638 TI - Wilbur J. Prezzano receives Albert H. Ketcham Memorial Award. PMID- 1636639 TI - Walter C. Buchsieb and James P. Kerrigan receive AAO Distinguished Service Awards. PMID- 1636640 TI - Four recipients of the 1991 B.F. and Helen Dewel Award. PMID- 1636641 TI - J. Douglas Ware receives Shepard Award. PMID- 1636642 TI - Dr. Goldstein receives the Medal of Achievement. PMID- 1636643 TI - The biomechanical effects of a sagittal split ramus osteotomy on the relationship of the mandible, the hyoid bone, and the cervical spine. AB - The effects of a sagittal split ramus osteotomy in correcting mandibular retrognathism and prognathism were studied cephalometrically in a group of 25 patients. The patients were divided into two groups, 18 patients with retrognathic mandibles and 7 patients with prognathic mandibles to be corrected by means of a sagittal split ramus osteotomy according to Obwegeser Dal Pont. The major complications of this type of surgical intervention have been documented in literature and are known as (1) a certain degree of relapse, i.e., mandibular instability and (2) the development of a permanently disturbed head balance. The displacement of the dental, skeletal, and neuromuscular components within the craniomandibular complex requires a large adaptive capacity and suggests that the patient will develop a forward head posture (anteroposition of the head) after both types of surgical intervention. In mandibular advancement, however, the initiating mechanism to develop a forward head posture starts in the cervicothoracic transition (C6-C7-T1-T2). In mandibular set-back, the discussed mechanism will start in the upper cervical area (C0-C1-C2-C3). The different pattern of movement of C2 and C3 in mandibular advancement and mandibular set back, respectively, confirmed the conclusion that the initiating mechanisms, may be found in the cervicothoracic transition and the upper cervical region, respectively. PMID- 1636644 TI - Oral water intoxication. PMID- 1636645 TI - Congenital hypocalcemia: transient or persistent? PMID- 1636646 TI - Hemorrhagic shock and encephalopathy syndrome. PMID- 1636647 TI - The brass standard. PMID- 1636648 TI - Hyperinsulinemic, hypertrophic cardiomyopathy in infancy. PMID- 1636649 TI - The effect of pediatric psychologic consultations on the management of adolescent suicide attempts in the pediatric service of a general hospital. PMID- 1636650 TI - The pediatrician's role in treating gay patients. PMID- 1636651 TI - Growing up: health care for adolescents and young adults with chronic conditions. PMID- 1636652 TI - Children of prisoners. PMID- 1636653 TI - Sudden infant death syndrome in neonates. PMID- 1636654 TI - Kindergarten screening tests accurately predict performance in kindergarten. PMID- 1636655 TI - Enhancing pediatric resident development through retreats. PMID- 1636656 TI - The escalating problem of antimicrobial resistance in Streptococcus pneumoniae. PMID- 1636657 TI - Antibiotic-resistant pneumococcal disease in South African children. AB - OBJECTIVE: To determine the incidence of antibiotic-resistant pneumococcal disease and to compare the presentation and outcome of penicillin-resistant infections with penicillin-susceptible infections. DESIGN: Patient series. SETTING: General community hospital. PATIENTS: Eighty-three children with penicillin-resistant pneumococcal bacteremia or meningitis and 124 children with penicillin-susceptible pneumococcal bacteremia or meningitis. SELECTION PROCEDURES: Consecutive patients admitted between 1989 and 1991. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Forty percent of community-acquired isolates and 95% of hospital-acquired isolates were resistant to penicillin. Eighty-three (82%) of 101 penicillin-resistant infections were community acquired. Resistance to chloramphenicol, tetracycline, and erythromycin occurred in 9%, 12%, and 4% of all isolates, respectively. The proportion of penicillin-resistant pneumococci with cefotaxime minimum inhibitory concentrations greater than or equal to 0.5 micrograms/mL increased from 0% in a 1986 study to 21.5% in this study. The sites of infection, underlying diseases, and mortality of patients with penicillin resistant infections outside the central nervous system did not differ significantly from those of penicillin-susceptible infections. CONCLUSIONS: The resistance of Streptococcus pneumoniae to beta-lactam antibiotics has increased alarmingly in South Africa. Penicillin-resistant and penicillin-susceptible pneumococcal infections cause a similar spectrum of illness. PMID- 1636658 TI - Patterns of infection after pediatric liver transplantation. AB - OBJECTIVE: To characterize the patterns of infection that occur after orthotopic liver transplantation in children. DESIGN: Inception cohort, retrospective. SETTING: Referral center for liver transplantation, university hospital. PATIENTS: Thirty-six consecutive children who underwent orthotopic liver transplantation and who survived for at least 48 hours after transplantation. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Twenty-six (72%) of the children had at least one infection, and infection caused four deaths. More infections occurred when prophylactic antilymphocyte antibodies were given than when they were not given (2.9 vs 1.0 infections per transplant). The risk of infection was greatest during the first 2 weeks after orthotopic liver transplantation. Most infections were caused by bacteria (52 cases), followed by viruses (16 cases) and fungi (11 cases). Bacteria were the most common pathogens during all periods, except the third and fourth weeks, when viruses predominated. The most common primary sites of bacterial infection were abdomen (15 cases), bloodstream (15 cases), and surgical wound (10 cases); the most frequent isolates were aerobic gram-negative bacilli (48% of isolates) and enterococci (19%). Cytomegalovirus was the most common viral pathogen (seven cases), and Candida albicans caused all fungal infections. Fungal infections were significantly associated with systemic antibiotic therapy and abdominal complications. CONCLUSIONS: Characteristic patterns of infection occur after pediatric orthotopic liver transplantation, and knowledge of these patterns is likely to result in improved care for transplant recipients. PMID- 1636659 TI - Mumps-associated acute cerebellar ataxia. AB - During a mumps outbreak between 1987 and 1988, six children presented with symptoms of acute cerebellar involvement as the sole neurologic complication. The neurologic symptoms followed parotitis and lasted for up to 3 weeks. Serologic evidence was suggestive of recent mumps infection. Symptoms spontaneously resolved in all patients without any residual signs or symptoms during 2- to 2.5 year follow-up. PMID- 1636660 TI - A survey of the structure and function of pediatric continuity clinics. AB - Continuity clinic is a mandated part of all accredited pediatric residency programs, yet there are minimal guidelines regarding structure and function. In 1988, we surveyed 101 residency programs, asking them to describe their continuity clinic experience. Eighty-seven residency programs (86%) responded to the 40-item questionnaire. The results showed clinics to be similar in many aspects, with consistent emphasis on developmental issues and anticipatory guidance. Areas of concern included lack of monitoring of the patient panel (31% did not monitor), excess care for chronic diseases or handicapping conditions (mean, 22% of patients), and lack of training in telephone advice (43% provided no such training). PMID- 1636661 TI - Unrecognized exercise-induced bronchospasm in adolescent athletes. AB - OBJECTIVE--As part of their preparticipation physical examinations, 1241 middle and high school student athletes completed a questionnaire and were interviewed to elicit risk factors for unrecognized exercise-induced bronchospasm (EIB). Spirometry was then performed when the students were at rest. RESEARCH DESIGN- All participants completed a questionnaire, were interviewed, and underwent baseline testing to determine forced expiratory volume in 1 second (FEV1). SETTING--All testing was performed in a school setting. SELECTION PROCEDURES- Athletes known to have EIB who were receiving appropriate treatment (46 athletes [4%]) and athletes with no risk factors based on medical history and normal results of spirometry (847 athletes [68%]) were eliminated from further evaluation. Students with medical histories indicating risk of unrecognized EIB and students with abnormal results of spirometry were eligible for exercise challenge by standard treadmill protocol. MEASUREMENTS AND RESULTS--Of the 348 eligible students, 230 (66%) completed the exercise challenge. Sixty-six of the 230 students had greater than 15% reduction in FEV1, and 50 of the 66 students had greater than 20% reduction, representing a 29% occurrence of previously undiagnosed EIB in a population of students identified with screening to be at risk of unrecognized EIB. Of the 179 students identified to be at risk based on medical history only, 28% had EIB. Of 33 students with positive results of spirometry but no medical history that put them at risk, 15% had EIB. Of the 18 students with medical histories that put them at risk and positive results of spirometry, 61% had EIB. Including the subpopulation with reduction in FEV1 of greater than 15%, students shown to be at risk after screening, and students previously identified as having EIB, 145 students were identified as having EIB (12%). CONCLUSIONS--These data are in accord with results of previously reported studies of college and Olympic athletes. The data may have implications for more extensive screening in the adolescent population. PMID- 1636662 TI - Radiological case of the month. Hydrocolpos in virilizing congenital adrenal hyperplasia. PMID- 1636663 TI - Radiological case of the month. Patent urachal duct. PMID- 1636664 TI - Picture of the month. Cutaneous vascular lesions. PMID- 1636665 TI - Synthetic surfactant replacement therapy decreases estimated pulmonary artery pressure in respiratory distress syndrome. AB - OBJECTIVE: To evaluate the effects of surfactant replacement therapy on the pulmonary artery pressure in infants with respiratory distress syndrome. DESIGN: Nonrandomized, "before-after" trial. SETTING: Neonatal intensive care unit at a referral center. PARTICIPANTS: Ten preterm infants with respiratory distress syndrome. INTERVENTIONS: Administration of two or four doses of an exogenous synthetic surfactant at 12-hour intervals. MEASUREMENTS AND RESULTS: Systolic pulmonary artery pressure was estimated by measuring tricuspid regurgitant flow velocity with the Doppler method before and, on average, 45 minutes after administration of synthetic surfactant. Measurable recordings were technically obtainable on 18 of 23 occasions. Surfactant instillation decreased pulmonary artery pressure significantly on 17 of 18 occasions, but did not change the systemic blood pressure. Twelve hours after surfactant treatment, pulmonary artery pressure measured on nine occasions returned to the pretreatment level. No change in the velocity or magnitude of the ductal left-to-right shunting due to exogenous surfactant was found. CONCLUSIONS: Synthetic surfactant replacement therapy in infants with respiratory distress syndrome induces a significant, but transient decrease in systolic pulmonary artery pressure with no effect on the ductal shunt. PMID- 1636666 TI - Agnogenic myeloid metaplasia in children. AB - Agnogenic myeloid metaplasia is a chronic myeloproliferative disorder characterized by splenomegaly, leukoerythroblastosis, extramedullary hematopoiesis, teardrop-shaped red blood cells, and fibrosis of the bone marrow. It is a disease of adults, with only one case report in the pediatric literature. The symptoms of the patient in this case clearly fit the diagnostic criteria of this disease. Myelofibrosis in children is usually of the acute type, presenting in infancy and running a fulminant, fatal course with minimal or mild splenomegaly. Red blood cells are usually normal on morphologic examination. Three infants, including two siblings, presented at ages 9, 10, and 16 months with clinical and laboratory findings consistent with agnogenic myeloid metaplasia. The occurrence of the disease in these siblings is suggestive of an autosomal recessive mode of inheritance. PMID- 1636667 TI - Infant deaths due to unintentional injury. An 11-year autopsy review. AB - OBJECTIVE: The number and causes of unintentional infant deaths were determined to identify common, preventable infant deaths. DESIGN: Retrospective autopsy review. SUBJECTS: Infants aged 1 day to 1 year undergoing complete autopsies. SETTING: Autopsies performed by the Louisville Office of the Kentucky Medical Examiner's Program from 1979 through 1989. METHOD: The manner of death was designated as an "accident" based on review of autopsy findings, scene investigation, and investigation by law enforcement officials. The cases were divided into groups based on the nature of the unintentional injury. RESULTS: Causes of death included asphyxia in mechanically unsafe sleeping environments, overlying, drowning, scald burns, plastic bag suffocation, house fires, motor vehicle collisions, aspiration of foreign bodies, hypothermia, blunt head trauma, and alcohol toxicity. The largest group of deaths in this series resulted from mechanically unsafe sleeping environments. CONCLUSIONS: The majority of deaths in this series could have been prevented by minor changes in the household environment. The causes of fatal unintentional injury to infants are different from those in older children. Pediatricians should be aware of hazards unique to this age group. PMID- 1636668 TI - The maturation of morphine clearance and metabolism. AB - OBJECTIVE: To determine how early in childhood the clearance of morphine sulfate reaches that in adults. DESIGN: Patient series. SETTING: Children's Hospital and Medical Center, Seattle, Wash. PARTICIPANTS: Forty-nine children aged 1 day to 2.5 years with normal renal and hepatic function. All children were receiving a constant rate intravenous infusion of morphine for postoperative analgesia for greater than 24 hours. INTERVENTIONS: Blood and urine samples were collected during infusion and immediately after discontinuation of the morphine infusion. MEASUREMENTS: Morphine concentrations were determined and clearance was calculated using the infusion data. Half-life and volume of distribution were calculated using the postinfusion data. The formation of metabolites was evaluated using the urine data. Morphine clearance increased with age, median clearances ranging from 5 mL/kg per minute in neonates aged 1 to 7 days to 21 mL/kg per minute in infants aged 6 months and older. This change in clearance correlated with age. The formation clearance of morphine glucuronide was correlated with age, whereas the formation clearance of morphine sulfate and the renal clearance of morphine were independent of age. CONCLUSIONS: Morphine clearance reaches adult values by age 6 months to 2.5 years. In contrast to previous reports on the maturation of sulfate conjugation, it does not appear that morphine sulfate clearance is enhanced relative to glucuronidation in early infancy. PMID- 1636669 TI - The importance of spirometry in the assessment of childhood asthma. AB - OBJECTIVE: To assess the pulmonary function of children with asthma at the time of a routine follow-up visit when they were judged to be clinically well. DESIGN: Pulmonary function tests were performed on children with a previous diagnosis of asthma. None had had any symptoms for at least 6 weeks. All had normal Wright peak flow rates and normal findings at physical examination. SETTING: General pediatric and pediatric pulmonary clinic at a municipal hospital in the Bronx, NY. PATIENTS: Sixty-five children with asthma who fit the above criteria. All were able to perform spirometry adequately. Their mean (+/- SD) age was 11 +/- 3 years, and their median age was 10 years. SELECTION PROCEDURES: All clinic patients were screened as possible participants. The 65 patients were deemed eligible, and were willing and able to perform spirometry. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The group's mean (+/- SD) forced expiratory volume in 1 second/forced vital capacity ratio was 80% +/- 8%, and their mean mid-maximal expiratory flow was 66% +/- 23% of the predicted value. Of the 65 patients, 11 (17%) had forced expiratory volume in 1 second/forced vital capacity ratios of less than 72%, and 35 (54%) had a mid-maximal expiratory flow of less than 65% of the predicted value. CONCLUSION: Failure to perform spirometry in children with asthma results in underdiagnosis of airflow obstruction. This may result in obstruction persisting into adulthood and/or progression to hyperinflation. PMID- 1636670 TI - National trends in pediatric resident recruitment. AB - Primary care residency programs throughout the nation are having increasing difficulty recruiting sufficient residents. Only 65% of pediatric residency positions are filled with medical graduates from the United States. We sent a questionnaire to pediatric residency program directors throughout the country to assess what changes pediatric programs had implemented in response to matching concerns. Forty-one percent had recruited non-house officer professionals to perform resident-type work. Such professionals included osteopathic and/or foreign-trained physicians (55%) and moonlighters (49%). House staff work hours had been reduced in 35% of programs and on-call frequency in 33%. Sixty-one percent had made significant changes in their recruiting practices in the past 5 years that are described herein. Annual recruiting budgets varied from nothing to over $75,000. This survey reveals widespread reduction in resident work load and increased intensity in the recruiting process throughout the country. PMID- 1636671 TI - Inflammatory cytokines within the central nervous system: sources, function, and mechanism of action. AB - In recent years, there has been increasing evidence that soluble mediators such as cytokines from activated T lymphocytes and macrophages are able to modulate the growth and function of cells found within the central nervous system (CNS), specifically macroglia and microglia cells. Furthermore, glial cells, upon activation, can secrete immunoregulatory factors that influence lymphoid/mononuclear cells as well as the glial cells themselves. Thus the potential exists for bidirectional communication between lymphoid cells and glial cells within the CNS, which in part is mediated via cytokines. This review describes various neurological disease states in which both immune and glial cells may contribute to inflammation and immunologic events occurring in the CNS. The mechanisms by which glial cells both respond to and synthesize a variety of cytokines within the CNS and the capacity of glial cells to acquire major histocompatibility complex antigens and function as antigen-presenting cells within the CNS are described in detail. The implications of these functions, cytokine secretion and antigen presentation, by glial cells are discussed with respect to neurological diseases associated with autoimmunity and/or inflammation. PMID- 1636672 TI - Protein kinase C affects microfilaments, bone resorption, and [Ca2+]o sensing in cultured osteoclasts. AB - The effects of protein kinase C (PKC) in the control of osteoclast activity are still unknown. We investigated the role of the enzyme in the control of microfilament organization, podosome assembly, bone resorption, and extracellular Ca2+ sensing in chicken and rabbit osteoclasts treated with agents known to affect PKC activity. Cells were treated for 20 min with a PKC activator [phorbol 12-myristate 13-acetate (PMA)], a PKC inhibitor (staurosporine), a protein kinase A (PKA) inhibitor (H-9), a guanosine 3',5'-cyclic monophosphate-dependent protein kinase-PKA-PKC inhibitor (H-7), or with the inactive phorbol, 4 alpha-phorbol, to examine microfilaments by decoration with rhodamine-phalloidin. In PMA-treated osteoclasts, the number of microfilament-containing adhesion structures (podosomes) per cell decreased. However, enlarged microfilamentous cores in podosomes and stress fiber-like filaments, otherwise absent in controls, appeared. Whereas H-7 induced increase of the number of podosomes, staurosporine, H-9, and 4 alpha-phorbol failed to change microfilament organization. Chicken osteoclasts received also long-term treatment with the agents in the presence of [3H]proline-prelabeled chicken or rat bone particles to measure bone resorption. PMA, as well as staurosporine and H-7, stimulated the resorbing activity, whereas cells were insensitive to H-9 and 4 alpha-phorbol. Measurement of cytosolic free calcium concentration in PMA-treated fura-2-loaded single osteoclasts demonstrated a synergistic effect of PKC activation on the inhibitory extracellular calcium concentration-sensing mechanism, which was, by contrast, blocked by H-7, staurosporine, and H-9 and was insensitive to 4 alpha-phorbol. These results indicate that PKC regulates osteoclast activity inducing both morphological and functional modifications. PMID- 1636673 TI - Protein kinase C does not participate in carbachol's secretory action in T84 cells. AB - We investigated the role of protein kinase C (PKC) in mediating carbachol's stimulation of transepithelial Cl- secretion in T84 cells. Direct PKC activation with phorbol 12-myristate 13-acetate (PMA) stimulated transepithelial Cl- transport (measured as the short-circuit current), demonstrating that PKC could interact with the secretory apparatus. Carbachol stimulated PKC activity, suggesting that the enzyme might participate in the hormone's action. Diacylglycerol metabolism inhibitors (DMIs), known to augment hormone-stimulated increases in diacylglycerol levels, potentiated the short-circuit current response to carbachol. The effect of DMIs was not due to amplification of carbachol-induced increases in PKC activity, however; PKC activity during carbachol stimulation was no higher in the presence of DMIs than in their absence. Augmentation of carbachol's action by DMIs appeared to be due to the direct activation of PKC which, like PMA, stimulated the Cl- conductance of the apical membrane (GCl). The effects of DMIs and carbachol on GCl were additive. Carbachol itself stimulated GCl but not by activating PKC; staurosporine did not blunt the effect of carbachol on GCl. Nor did staurosporine reduce the effect of carbachol on transepithelial Cl- secretion. These observations demonstrate that PKC does not participate in the secretory action of carbachol in T84 cells and suggest that direct PKC activation with DMIs and PMA stimulates an apical pool of PKC that is not accessible to carbachol applied to the basolateral membrane. PMID- 1636674 TI - Characteristics of membrane currents evoked by photoreleased inositol trisphosphate in Xenopus oocytes. AB - Photorelease of inositol 1,4,5-trisphosphate (InsP3) from a caged precursor was used to study characteristics of Ca(2+)-activated Cl- currents activated in Xenopus oocytes by the InsP3-Ca2+ signaling pathway. Photolysis flashes shorter than a threshold duration evoked no response, but the current amplitude then grew about linearly as the flash duration was further lengthened. Currents directly evoked by photorelease of Ca2+ from a caged precursor grew linearly with increasing flash duration and showed a small threshold before they were activated. However, the major part of the threshold of InsP3-evoked responses appears to arise because a certain concentration of InsP3 (estimated to be approximately 60 nM) is required to evoke Ca2+ liberation. Subthreshold conditioning flashes potentiated responses to subsequent flashes, and the potentiation increased linearly with increasing conditioning flash duration before abruptly declining. The potentiation decayed exponentially with a time constant of approximately 17 s with increasing interflash interval. Currents evoked by photoreleased InsP3 began after a latency that shortened from 10 s or longer to 100 ms as the photolysis intensity was increased. This dose dependence of the latency could be quantitatively explained by the time required for the InsP3 concentration to rise above threshold. Intracellular injection of heparin (a competitive antagonist at the InsP3 receptor) increased the threshold for InsP3 action, as did increased temperature. We conclude that several characteristics of InsP3-evoked responses, including their dose dependence, latency, and facilitation with paired stimuli, arise because a distinct threshold level of InsP3 is required to evoke release of Ca2+ from intracellular stores. PMID- 1636675 TI - Effect of forskolin on conductive anion pathways of toad skin. AB - The effect of the diterpene, forskolin, on pathways for conductive Cl- transport was analyzed using isolated skins of Bufo viridis. Forskolin did not stimulate the voltage-activated Cl- movement from mucosa to serosa; the Lorentzian component in the power density spectrum, which was present at serosa positive clamp potentials under control conditions, decreased significantly. The observation that stimulation of cytosolic adenosine 3'-5'-cyclic monophosphate (cAMP) by forskolin has no effect on the voltage-activated Cl- transport argues against control of this pathway by cAMP. Our data further demonstrate that the forskolin-activated Cl- conductive pathway is also permeable for NO3-. This pathway was studied in absence of mucosal Cl-, which eliminates Cl- movement through the voltage-activated pathway. With SO4(2-) and Cl- on the mucosal and serosal sides, respectively, this forskolin-induced pathway displayed a linear current-voltage relationship. The associated Lorentzians increased at serosa negative clamp potentials. Transepithelial current and plateau value of the Lorentzian were related by a quadratic function, which suggests voltage independence of number and open-close probability of these conductance sites. Morphological sites for voltage-activated and forskolin-induced conductive Cl- transport remain to be identified. PMID- 1636676 TI - Metabolic substrates can alter postischemic recovery in preconditioned ischemic heart. AB - The mechanisms that contribute to myocardial cell injury are not well understood. Furthermore, the ability of reperfusion conditions to modify ischemic injury is unclear. Recent studies have indicated that glucose utilization may improve ionic homeostasis. Because considerable derangement of ion concentrations occurs during ischemia, glucose utilization may be beneficial when stimulated during the reperfusion period. The effects of glycolytic vs. mitochondrial substrates on postischemic contractile function, high-energy phosphates and ion balance (intracellular Ca2+ and pH) were determined. Reperfusion conditions were compared in the "preconditioned ischemic" heart where baseline contractile recovery during reperfusion with glucose as the sole exogenous substrate was 74 +/- 5% (n = 10). Contractile recovery was determined for reperfusion with pyruvate (14 +/- 2%, n = 10), pyruvate+glucose (23 +/- 4%, n = 10), deoxyglucose+acetate (25 +/- 4%, n = 10), and lactate+glucose (60 +/- 11%, n = 10). Contractile dysfunction could not be attributed to differences in high-energy phosphate contents. Elevated levels of intracellular Ca2+ during reperfusion were, however, correlated with poor contractile function. After 20 min of reperfusion, the mean time-averaged intracellular Ca2+ values, measured with 19F-nuclear magnetic resonance of 5 fluoro-1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-loaded hearts, were 994 +/- 110 nM (glucose, n = 5), 2,270 +/- 494 nM (pyruvate, n = 5), 2,671 +/- 419 nM (pyruvate+glucose, n = 5), 2,382 +/- 480 nM (deoxyglucose+acetate, n = 5), and 1,019 +/- 33 nM (lactate+glucose, n = 5). These results are consistent with a beneficial role for glucose utilization during reperfusion, where enhanced recovery of contractile function and ionic homeostasis were observed. PMID- 1636677 TI - Regulated expression of monocyte chemoattractant protein-1 in normal human osteoblastic cells. AB - An influx of monocytes is observed in many different physiological and pathophysiological states, including bone remodeling and injury. These cells appear at early stages of bone formation and repair and persist throughout the later stages. In experiments described here, unstimulated normal human osteoblastic cells did not produce detectable levels of monocyte chemotactic activity. However, interleukin-1 (IL-1)-stimulated normal human osteoblastic cells produced a chemoattractant that is similar to monocyte chemoattractant protein-1 (MCP-1) at the levels of mRNA expression, protein production, and chemotactic activity. Northern blot analysis indicates that IL-1 elicits a dose dependent increase in MCP-1 mRNA in normal human osteoblastic cells. Two proteins of M(r) 9,000 and M(r) 13,000 were specifically immunoprecipitated with MCP-1 antiserum from IL-1-stimulated normal human osteoblastic cells. Monocyte chemotactic activity from IL-1-treated cells was blocked by MCP-1 antiserum. These studies establish that normal human osteoblastic cells can be induced to produce monocyte chemoattractants and that this is accounted for by the induced expression of MCP-1. PMID- 1636678 TI - Citrate transport in proximal cell line. AB - Citrate uptake into kidney proximal tubules occurs via an apical dicarboxylate transporter and a poorly characterized process in the basolateral membrane. We used OK cells, a cell line derived from opossum kidney, to study citrate transport in proximal tubule-like cells. Citrate uptake into cell monolayers was studied using [14C]citrate with [3H]mannitol as a volume marker. Citrate uptake into these cells was sodium dependent and saturable with increasing concentrations of citrate. In contrast to previous models, citrate transport was altered minimally by changes in pH from 6.2 to 7.0 and increased at pH 7.4 to 7.8. A variety of di- and tricarboxylates were tested for interaction with citrate transport. The dicarboxylates succinate, malate, and oxaloacetate at 1 mM concentration inhibited citrate uptake minimally (uptake at least 80% of control); one dicarboxylate, alpha-ketoglutarate, did inhibit citrate uptake significantly. In contrast, the tricarboxylates isocitrate and tricarballylate inhibited citrate uptake significantly, indicating probable competitive inhibition with the transport process. These characteristics are distinctly different from those of the apical membrane dicarboxylate transporter. 1,2,3 Benzenetricarboxylic acid, an inhibitor of the mitochondrial tricarboxylate transporter, did not alter citrate uptake. In conclusion, the OK proximal cell line exhibits a novel citrate transport process compared with the apical transport of citrate described in most proximal systems. This transport process probably involves the trivalent species of citrate in contrast to the usual predominant transport of divalent citrate. This transport process may represent a process similar to that in the basolateral membrane of the proximal tubule. PMID- 1636679 TI - Participation of fast-activating, voltage-dependent K currents in electrical slow waves of colonic circular muscle. AB - The plateau phase of electrical slow waves in phasic gastrointestinal muscles is critical for excitation-contraction coupling. The plateau appears to depend upon a balance between inward Ca2+ current and outward K+ currents that is sustained for several seconds. Voltage-dependent, non-Ca(2+)-dependent K currents were studied in canine colonic circular muscle cells using the whole cell patch-clamp technique. At room temperature, depolarization activated a slow outward current that showed little inactivation during 500 ms. Increasing the temperature to 37 degrees C significantly increased the rate of activation of voltage-dependent outward current. The onset of the outward current overlapped the transient inward Ca2+ current, suggesting that this K current may act as a brake on the upstroke depolarization of electrical slow waves in intact muscles. Voltage-dependent outward current was sustained for the duration of test pulses. This current balanced the sustained inward current that was also activated at physiological test potentials. The outward current evoked by test pulses positive to -20 mV inactivated by at least 50% within 500 ms. Half inactivation occurred at -36 mV. Voltage-dependent K current was reduced by 4-aminopyridine (4-AP; 1-5 mM), but difference currents obtained by subtracting currents elicited from holding potentials of -45 mV from currents obtained from holding potentials of -100 mV were not affected by 4-AP (1 mM). Studies were also performed on intact muscles to test the effects of 4-AP on electrical slow waves. 4-AP increased the amplitude and rate of rise of the upstroke potential and increased the amplitude and prolonged the plateau phase of slow waves. These data suggest that a rapidly activating, inactivating, voltage-dependent K current participates in electrical slow waves of colonic circular smooth muscles. PMID- 1636680 TI - Interferon-gamma is an inducer of plasminogen activator inhibitor type 1 in human orbital fibroblasts. AB - Expression of plasminogen activator inhibitor type 1 (PAI-1), an important determinant of the pericellular proteolytic environment, was assessed in cultured human orbital and dermal fibroblasts. Bidimensional electrophoretic separation of total cellular [35S]methionine-labeled proteins revealed multiple isoforms of the 50-kDa PAI-1 protein (isoelectric point range 5.6-6.3) expressed in dermal strains but not in orbital cultures. The addition of human recombinant interferon gamma (100 U/ml) to the media for 48 h resulted in a marked induction of PAI-1 in the orbital cultures (greater than 50-fold above baseline), whereas the expression in dermal cultures was either attenuated or induced modestly (5-fold). The identity of the 50-kDa PAI-1 was verified by immunoprecipitation of secreted proteins. Indirect immunofluorescence localized PAI-1 to aggregates at the ventral undersurface of the monolayer. Interferon-gamma induced several other proteins in cultured cells. The observation that untreated orbital fibroblasts do not express detectable cell-associated PAI-1 suggests that the pericellular proteolytic environment of these cells is regulated ordinarily by other factors. The economy of the extracellular matrix of orbital connective tissue may be particularly susceptible to the influence of inflammatory cytokines such as interferon-gamma. PMID- 1636681 TI - Diverse prostaglandin receptors activate distinct signal transduction pathways in rat myometrium. AB - Attempts were made to identify prostaglandin (PG) receptors in rat myometrium, according to the differential rank order of potencies displayed by the natural PGs and their analogues, both at the level of second messenger generation and contraction. In estrogen-treated rat myometrium, PGs [iloprost = PGI2 greater than PGE2 much greater than 16,16-dimethyl (DM)-PGE2; sulprostone = misoprostol = 0] induced adenosine 3',5'-cyclic monophosphate generation, indicating the contribution of a PGI2 receptor. The generation of inositol phosphates was stimulated by PGs (PGF2 alpha greater than PGD2 much greater than PGE2 = DM-PGE2 much greater than iloprost greater than sulprostone = misoprostol = 0), reflecting a PGF2 alpha-receptor-mediated process, which was insensitive to pertussis toxin (PTX). Contractions caused by PGF2 alpha were closely correlated to PGF2 alpha-receptor activation associated with the phospholipase C pathway. By contrast, contractions evoked by PGE2, equally mimicked by sulprostone and misoprostol, were abolished by PTX and were independent of phospholipase C activation. In the pregnant myometrium (day 21), the latter PGE-receptor-mediated mechanism also contributed to contractions caused by PGE2 (less than microM concn). Phospholipase C activation was coupled not only to PGF2 alpha but also to PGE receptors and could be correlated with contractions induced by PGF2 alpha and PGE2 greater than microM concn). All PGs tested were coupled to inhibitory G protein-mediated adenylate cyclase inhibition, displaying an equipotency that did not allow characterization of the inhibitory PG receptors. PMID- 1636682 TI - Heat shock increases cytosolic free Ca2+ concentration via Na(+)-Ca2+ exchange in human epidermoid A 431 cells. AB - This study characterized cytosolic free Ca2+ concentration ([Ca2+]i) in normal and thermally injured human epidermoid A 431 cells. The resting [Ca2+]i in normal cells at 37 degrees C was 87 +/- 5 nM (n = 105). When cells were subjected to hyperthermia (40-50 degrees C), [Ca2+]i increased in a temperature- and time dependent manner. The maximal increase in cells exposed to 45 degrees C was observed at 20 min; [Ca2+]i returned to normal within 1 h. The heat-induced [Ca2+]i increase depended on the presence of external Ca2+. La3+ and Cd2+ but not Co2+, verapamil, or nifedipine attenuated the heat-induced [Ca2+]i increase. TMB 8 partially blocked the increase in [Ca2+]i but pertussis toxin and cholera toxin pretreatment did not. The magnitude of the heat-induced [Ca2+]i increase or 45Ca2+ uptake depended on the presence of extracellular Na+. Heat treatment reduced the apparent Michaelis constant for external Ca2+ from 490 +/- 91 to 210 +/- 60 microM, whereas the maximal velocity remained the same. The intracellular Na+ concentration decreased 62.5% after heating. The heat-induced [Ca2+]i increase was completely blocked by amiloride (5 microM) and 5'-(N,N-dimethyl) amiloride (1 microM). These results suggest heat activates the Na(+)-Ca2+ exchange system so as to increase [Ca2+]i and reduce [Na+]i. PMID- 1636683 TI - Ammoniagenesis in LLC-PK1 cultures: role of transamination. AB - The LLC-PK1 renal epithelial cell line has been used as a model system to study renal ammoniagenesis and its regulation by metabolic acidosis in vitro. Experiments were performed on confluent LLC-PK1 epithelia grown for 10-14 days in conventional monolayer technique. After the medium pH was changed from 7.6 to 7.0 for 24-72 h by lowering the bicarbonate concentration in culture medium, LLC-PK1 cells responded with an adaptive increase in glutamine consumption and ammonia production. The rates of glutamine uptake and ammonia generation displayed a ratio of 1:1, i.e., 1 mol ammonia was produced per mole of glutamine consumed. Glutamine consumption and ammonia formation were paralleled by an equimolar production of L-alanine, indicating that transamination appears to be the main ammoniagenic pathway in LLC-PK1 cells. Analysis of the key enzymes of renal ammoniagenesis, phosphate-dependent glutaminase (PDG) and glutamate dehydrogenase (GDH), revealed no changes in enzyme activities up to 72 h of adaptation. Alanine aminotransferase (ALT) activity in LLC-PK1 cells also remained unchanged during the adaptation period. Because transamination seems to play a crucial role in channeling the metabolic flux in LLC-PK1 ammoniagenesis, experiments were performed in which transamination was inhibited by (aminooxy)acetate (AOA). After incubation of control and pH 7.0-adapted LLC-PK1 cultures for 24-72 h in 0.2 mM AOA, no alanine production was found, but 2 mol of ammonia were formed per mole of glutamine consumed, again, without adaptive changes in PDG and GDH activities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636684 TI - Activation of permeabilized neutrophils: role of anions. AB - Activation of neutrophils was recently reported to be accompanied by large changes in their Cl- content [J. B. Myers, H. F. Cantiello, J. H. Schwartz, and A. I. Tauber. Am. J. Physiol. 259 (Cell Physiol. 28): C531-C540, 1990]. The significance of these ionic changes to the immune response has not been studied. To evaluate the role of intracellular [Cl-], the anionic composition of the cytosol was varied in human neutrophils permeabilized by electroporation or by treatment with streptolysin O. In Cl(-)-rich media, permeabilized but otherwise untreated cells remained quiescent, resembling unstimulated intact cells. In contrast, suspension of permeabilized cells in Cl(-)-depleted media elicited protein phosphorylation, actin polymerization, secretion of lysozyme, and a respiratory burst. The latter was demonstrated by several criteria to be mediated by the NADPH oxidase. The responses observed in Cl(-)-depleted media were insensitive to pretreatment of the cells with pertussis toxin but were inhibited by addition of GDP or by omission of ATP. The data suggest that an early event in signal transduction, common to several effectors, is sensitive to the ionic composition of the cytosol. This component, possibly a GTP-binding protein, may be affected by the anion concentration changes reported to occur during physiological stimulation of neutrophils. PMID- 1636685 TI - Glucose utilization and insulin action in adult rats submitted to prolonged food restriction. AB - Glucose tolerance and insulin effects on glucose production and utilization by various tissues were studied in 70-day-old anesthetized rats submitted to food restriction from the fetal stage. Basal and glucose-induced plasma insulin levels were reduced in food-restricted rats without alterations in glucose tolerance. Insulin action was quantified by using the euglycemic-hyperinsulinemic clamp technique. Glucose turnover rates were measured by using D-[6-3H]glucose. Exogenous insulin failed to decrease glucose production in food-restricted rats. Weight-related whole body glucose utilization was higher in restricted rats than in controls both in the basal (21.9 +/- 0.7 vs. 9.4 +/- 0.6 mg.min-1.kg-1) and hyperinsulinemic states (37.5 +/- 1.1 vs. 14.0 +/- 1.2 mg.min-1.kg-1). Local glucose utilization by peripheral tissues was estimated by a 2-deoxy-D-[1 3H]glucose technique. In both basal and hyperinsulinemic conditions glucose utilization was increased in various adipose and muscle tissues of the food restricted rats as compared with the controls. Thus we conclude that food restriction leads to an increase in the insulin-mediated glucose uptake by various peripheral tissues and to insulin resistance in the liver. PMID- 1636686 TI - Developmental expression of insulin-regulatable glucose transporter GLUT-4. AB - The insulin-regulatable glucose transporter (GLUT-4) is expressed in adipose tissue and in cardiac and skeletal muscle (D. E. James, R. Brown, J. Navarro, and P. F. Pilch. Nature Lond. 333: 183-185, 1988). We examined GLUT-4 development between postnatal days 1 and 41 (P1-P41) in male and female rats in these tissues by quantitative immunoblotting. GLUT-4 was detectable in each tissue at comparable levels at P1. However, the subsequent patterns of GLUT-4 development were distinctive. GLUT-4 increased in the diaphragm after P7, peaked at P20, and then declined. GLUT-4 expression in the heart increased rapidly after P7 to plateau on P41 at levels four times greater than the diaphragm. In sharp contrast, adipose tissue expression was highest between P3 and P5 but declined to a nadir at P20 before rebounding at P34. These patterns were observed for both sexes within each tissue, but female GLUT-4 expression was higher in diaphragm and heart and lower in adipose tissue. The expression of GLUT-4 appears to be regulated in a tissue-specific manner by a developmental program that may coordinate the expression of other proteins of metabolic importance. PMID- 1636687 TI - Osteocalcin and its message: relationship to bone histology in magnesium-deprived rats. AB - These studies examine effects of brief Mg deprivation on bone histomorphometry and on secretion and synthesis of the specific osteoblast product, osteocalcin. Osteocalcin mRNA was determined in calvaria-derived cells and was correlated to circulating concentrations of the protein after 8 days of Mg deprivation. Circulating osteocalcin was decreased in Mg-deprived rats when compared with pair fed normal rats after 8 days of Mg deprivation, with no significant changes in calcium or 1,25-dihydroxyvitamin D [1,25(OH)2D]. Serial sampling demonstrated a difference in osteocalcin levels by 2 days of Mg deprivation, before any changes in circulating calcium or parathyroid hormone were present. Although circulating osteocalcin is decreased in Mg-deprived animals, levels can be stimulated with 1,25(OH)2D3. Osteocalcin mRNA is reduced after Mg deprivation, suggesting that low circulating levels are due, at least in part, to reduced osteocalcin synthesis. Mg-deprived rats had diminished bone volume and abnormal histological features consistent with disorganized and chaotic bone remodeling. These findings indicate that low-Mg intake during growth can alter the quality and quantity of bone and suggest that Mg deprivation may contribute to the development of osteoporosis. PMID- 1636688 TI - Decreased T4-to-T3 conversion in brown adipose tissue of Zucker fa/fa pups before the onset of obesity. AB - To determine whether the capacity of thyroxine (T4)-to-3,5,3'-triiodothyronine (T3) conversion was altered in Zucker fa/fa pups, we measured thyroxine 5' monodeiodinase (T(4)5'D) activity in brown adipose tissue (BAT) and liver of suckling and weaned fa/fa and Fa/fa littermates. In suckling fa/fa compared with Fa/fa rats, T(4)5'D was reduced by 30-55% in BAT and slightly increased in liver, while serum free T3 was significantly decreased (-30%). Altered T(4)5'D activity in BAT of fa/fa pups could be corrected by adrenergic stimulation. After weaning, in fa/fa rats, the capacity for T4-to-T3 conversion was totally restored in BAT while it was dramatically reduced in liver. The concentration of serum free T3 remained lower in fa/fa than in Fa/fa rats (-40%). These data confirm that BAT is a very early site of fa gene expression and are consistent with the hypothesis that a defect in the autonomic nervous system may be a primary cause of this genetic obesity. It is also suggested that, during suckling, BAT plays an important role in systemic production of T3. PMID- 1636689 TI - Relationship between aerobic fitness level and daily energy expenditure in weight stable humans. AB - The relationship between exercise and energy expenditure is unclear, with some suggestions that exercise leads to increased energy expenditure over and beyond the increase due to the exercise itself. In this cross-sectional study, we examined the relationships among aerobic fitness level, body composition, and total daily energy expenditure in 78 subjects. Daily energy expenditure (determined in a whole room calorimeter) was significantly correlated with both fat-free mass (FFM) and aerobic fitness (estimated from maximum aerobic capacity or VO2max). However, multiple-regression analysis demonstrated that, after accounting for FFM, VO2max did not explain a significant amount of the remaining variation in energy expenditure. In addition, the relationship between resting metabolic rate and both FFM and VO2max was evaluated using data from 214 weight stable subjects analyzed retrospectively. The results were identical with the results obtained from the 78 subjects in that VO2max did not have effects independent of FFM on energy expenditure. We conclude that aerobic fitness does not have a direct effect on energy expenditure. However, it may have effects that are mediated through body composition, since in both populations studied here, VO2max was positively correlated with FFM and negatively correlated with adiposity. PMID- 1636690 TI - Thermogenic and hormonal responses to amino acid infusion in septic humans. AB - Metabolic effects of a commercially available amino acid infusate were investigated in five preoperative patients with abdominal sepsis and five healthy subjects. Oxygen consumption (VO2) was measured continuously during the 3-h study, and blood samples were taken regularly for hormone and metabolite analyses. During 1 h of preinfusion measurements, VO2 was 15% higher (P less than 0.05) in the septic patients. Preinfusion plasma cortisol, glucagon, and catecholamines were also significantly elevated in the septic group. The amino acid solution (9 g nitrogen; 950 kJ; 227 kcal) was infused into each subject through their central venous catheter during the 2nd and 3rd h of the study. VO2 increased similarly in both groups by approximately 21% during the infusion (P less than 0.05), whereas respiratory quotient increased significantly in only the controls (P less than 0.05). Plasma insulin and glucagon concentrations rose significantly in both groups during the infusion, despite little change in glucose levels. Plasma norepinephrine increased in both groups, although the response was significant in only the control subjects. In summary, the amino acid infusate stimulated metabolic rate similarly in the septic and nonseptic subjects. PMID- 1636691 TI - Prednisone-induced osteopenia in beagles: variable effects mediated by differential suppression of bone formation. AB - To examine the mechanism of glucocorticoid-induced osteopenia and the basis for variable bone loss after glucocorticoid administration, we gave prednisone (1.3 mg.kg-1.day-1) to normal male dogs (n = 15) for 29 wk to attempt induction of osteopenia. Compared with age-matched control dogs (n = 14), prednisone treatment rapidly decreased spinal bone density by 4.3%, as assessed by quantitative digital radiography, and reduced trabecular bone volume by 14.6%, as measured by quantitative histomorphology of iliac crest bone specimens. Bone loss was attenuated in prednisone-treated dogs after prolonged treatment (greater than 12 wk). Prednisone treatment resulted in diminished bone formation rates (15 +/- 3.4 vs. 47 +/- 4.5 microns/yr) and activation frequency (0.4 +/- 0.1 vs. 1.3 +/- 0.2/day). These findings indicate that suppression of osteoblastic function and recruitment is the primary histological abnormality mediating glucocorticoid induced osteopenia in beagles. In contrast, prednisone administration had no effect on bone resorption or serum concentrations of parathyroid hormone and 1,25 dihydroxyvitamin D, which suggests that these factors are not essential for prednisone-induced bone loss. Moreover, 33% of beagles were totally resistant to glucocorticoid-induced osteopenia. Such heterogeneity of bone loss was associated with variable suppressive effects of prednisone on osteoblastic function, as evidenced by greater bone formation rates and activation frequency in prednisone resistant animals. Collectively, these observations suggest that glucocorticoid induced bone loss results from a dynamic interplay between steroid-mediated suppression of osteoblastic function and recruitment and undefined compensatory factors that ameliorate the effects of glucocorticoids on osteoblastic precursors. PMID- 1636692 TI - Epidermal growth factor prohormone is secreted in human urine. AB - Examination of adult human urine by immunoblot analysis with antiserum specific to human recombinant 6-kDa epidermal growth factor (EGF) reveals the presence of an immunoreactive protein with a molecular mass of 165 kDa. This protein is consistently found in the morning (first) but not in day urine of adult males and females. Day urine contains variable proportions of four other high-molecular weight EGFs with approximate molecular masses of 97, 66, 50, and 42 kDa. The 165 kDa EGF immunoreactive protein reacts with mouse amino-terminal EGF prohormone (proEGF) antiserum and comigrates with mouse urinary proEGF, suggesting that the protein is the human EGF prohormone. The 165-kDa human proEGF exhibits strong binding affinity to concanavalin A, indicating that it is glycosylated. Immunoblotting of urine in infants and children of various age groups demonstrates the presence of proEGF in all age groups, but its concentration is highest in children 2-4 yr of age. These findings, taken together with secretion of proEGF of similar molecular mass in mouse and rat urine, suggest that renal proEGF secretion is an evolutionarily conserved phenomenon and may have an important function or functions distal to the site of its synthesis. PMID- 1636693 TI - Erectile and copulatory dysfunction in chronically diabetic BB/WOR rats. AB - The pituitary-testicular axis, penile reflexes, and copulatory behavior were studied in male BB diabetic rats from 10 to 40 wk of diabetes. Serum testosterone was diminished from 18 to 28 wk of diabetes, and the responses to human chorionic gonadotropin stimulation were blunted. Serum luteinizing hormone (LH) in diabetic rats did not differ from that of the control rats before or after LH-releasing hormone stimulation. Serum follicle-stimulating hormone and prolactin levels were also similar to controls. After 26 wk of diabetes, androgen-sensitive reproductive accessory organs were significantly reduced in size. This also was true for the androgen-sensitive bulbocavernosus and ischiocavernosus muscles. Penile reflexes in these animals from 20 to 32 wk of diabetes were consistently reduced in number and demonstrated prolonged latency. Copulatory behavior was evaluated in these animals at 25 and 28 wk of diabetes and revealed a reduced number of BB diabetic rats showing normal behavior at 25 wk of diabetes. At 28 wk of diabetes, mount latency, intromission latency, ejaculatory latency, and the postejaculatory interval were all prolonged compared with controls. In addition, the number of diabetic animals showing normal behavior was reduced compared with controls. These studies demonstrate that chronically BB diabetic rats develop diminished testosterone and erectile dysfunction that precedes ejaculatory dysfunction in a similar fashion as impotence in diabetic men. We suggest that further studies in this animal model may be critical to the better understanding and treatment of impotence in diabetic men. PMID- 1636694 TI - Role of GH in regulating nocturnal rates of lipolysis and plasma mevalonate levels in normal and diabetic humans. AB - To define the role that nocturnal increments in growth hormone (GH) play in maintaining lipolysis, glycerol turnover was measured in six patients with GH deficiency and six normal subjects during sleep. Glycerol production initially decreased in both groups but then increased to 1.44 +/- 0.20 mumol.kg-1.min-1 by 0800 h in normal subjects, whereas GH deficiency was associated with a continuous fall to 0.77 +/- 0.10 mumol.kg-1.min-1, P less than 0.02. Nonesterified fatty acid levels paralleled these changes. Six GH-deficient patients received basal GH replacement including a pulse during sleep, which resulted in normal fasting fatty acid levels (P less than 0.05, replaced vs. chronic deficiency). To assess a possible link between the normal nocturnal increase in plasma mevalonate (the product of the rate-limiting step in cholesterol synthesis) and sleep-associated GH release, 11 GH-deficient patients and 11 normal subjects were studied. Peak nocturnal and fasting mevalonate concentrations were not correlated with GH level. We conclude that nocturnal growth hormone secretion is essential for maintaining lipolysis but that it is not related to normal increments in mevalonate and, by inference, to cholesterol synthesis during sleep. PMID- 1636695 TI - Use of [3-3H]glucose and [6-14C]glucose to measure glucose turnover and glucose metabolism in humans. AB - [3-3H]glucose is frequently used to measure glucose turnover in humans. If fructose 6-phosphate-fructose 1,6-diphosphate cycling (Fpc) is negligible in both liver and muscle, then [3-3H]- and [6-14C]glucose (corrected for Cori cycle activity) should provide equivalent measures of glucose turnover. In addition, if glycogenolysis is fully suppressed, then [14C]lactate specific activity should equal that of [6-14C]glucose from which it was derived, and oxidation of [6 14C]glucose, as measured by rate of generation of 14CO2, should equal total glucose oxidation (i.e., that derived from intra- and extracellular pools) as measured by indirect calorimetry. To address these questions, glucose turnover was measured simultaneously with [3-3H]- and [6-14C]glucose in the basal state and in presence of low (approximately 200 pM) and high (approximately 750 pM) insulin concentrations. Glucose turnover rates measured with [3-3H]- and [6 14C]glucose were equivalent at all insulin concentrations, indicating that Fpc had no detectable effect on measurement of glucose appearance. [14C]lactate specific activity was lower (P less than 0.01) than that of [6-14C]glucose in the basal state but not during either low- or high-dose insulin infusion, implying that all lactate was derived from extracellular glucose. On the other hand, glucose oxidation as measured by rate of generation of 14CO2 was lower (P less than 0.05) than glucose oxidation as measured by indirect calorimetry during both insulin infusions, implying either that suppression of glycogenolysis was not complete in all tissues or that one or both of these techniques do not accurately measure glucose oxidation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636696 TI - Plasma leucine kinetics and urinary nitrogen excretion in intensively treated diabetes mellitus. AB - It is well known that inadequate insulin therapy stimulates body protein loss in insulin-dependent diabetes mellitus (IDDM). It is less well known, however, that accelerated body protein loss (as indicated by increased leucine oxidation) occurs in IDDM even during conventional glycemic control. It is not known whether intensified insulin therapy fully normalizes protein oxidation or, more importantly, whether such therapy is sufficient to allow the adaptive decrease of protein oxidation that normally occurs when protein intake is restricted below the customary surfeit level. We used two measures of protein oxidation [daily urinary nitrogen (N) excretion over several days of intensive insulin therapy and plasma [1-13C]leucine oxidation during short-term strict euglycemia] to assess the response of 7 men with IDDM and 12 normal men after adaptation first to a control diet providing maintenance energy and conventional (surfeit) protein then to an isoenergetic protein-free diet. After adaptation to the protein-free diet and during short-term strict euglycemia achieved using intravenous insulin, leucine turnover and oxidation decreased equivalently in normal and diabetic subjects. However, daily urinary obligatory N excretion, which indicated the effect of the low-protein diet and intensive subcutaneous insulin therapy over several days, was increased by 18% in the diabetic group (P less than 0.05). Even mildly elevated average blood glucose values well within the guidelines for intensive therapy were strongly correlated with high rates of urinary N excretion (r = 0.97, P = 0.0002). Thus insulin therapy of IDDM that imposes strict euglycemia is compatible with a normal ability to diminish body protein oxidation in response to protein restriction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636697 TI - Free and sulfoconjugated catecholamine responses at birth in newborn sheep. AB - There have been little data on catecholamine sulfoconjugation in developing animals or humans. We studied the differences in free and sulfoconjugated catecholamines at birth in newborn sheep. Baseline concentrations of sulfoconjugated norepinephrine and epinephrine were the predominant form of circulating catecholamine, representing 77 +/- 4 and 65 +/- 12% of total circulating catecholamines, respectively. At birth the free epinephrine concentration increased 10-fold (49 +/- 27 to 653 +/- 21 pg/ml, respectively), and plasma free norepinephrine concentration rose 4-fold (307 +/- 92 to 1,178 +/- 389 pg/ml). In contrast, there was only a transient twofold increase in the sulfoconjugated epinephrine. There was no increase in the sulfoconjugated form of norepinephrine. These data demonstrate that, while the near-term newborn sheep has a well-developed mechanism for sulfoconjugation of circulating catecholamines, this does not occur rapidly. During the logarithmic increases of circulating catecholamines at birth, there are not commensurate increases in the concentration of sulfoconjugated norepinephrine or epinephrine. Thus sulfoconjugation does not appear to represent a significant mechanism for inactivation of the high circulating levels of catecholamines seen at birth. PMID- 1636698 TI - Dose-response characteristics of human proinsulin and insulin in non-insulin dependent diabetic humans. AB - We compared the actions of human proinsulin and insulin on glucose turnover and on intermediary carbohydrate and lipid metabolism in non-insulin-dependent diabetes mellitus (NIDDM). Six diet-controlled weight-matched (25.4 +/- 1.0 kg/m2) NIDDM subjects underwent six separate isoglycemic clamps. Glucose turnover was measured using a primed continuous infusion of [6',6'-2H2]glucose. Each subject received three low-dose intravenous infusions of both insulin and proinsulin. Blood glucose was maintained at 6.7 +/- 0.3 mM during proinsulin and insulin infusion. Insulin (I) infusions gave steady-state levels of 0.12 +/- 0.001 (I1), 0.18 +/- 0.01 (I2), and 0.33 +/- 0.01 nM (I3). Steady-state proinsulin (P) levels were 2.5 +/- 0.1 (P1), 4.3 +/- 0.2 (P2), and 8.8 +/- 0.9 nM (P3). Hepatic glucose production was suppressed equally by proinsulin and insulin at all doses. The metabolic clearance rate of glucose was significantly increased during the insulin infusion compared with proinsulin. The use of [6',6' 2H2]glucose resulted in a mean underestimation of the glucose infusion rate of 10.0 +/- 4.0 and 6.0 +/- 2.5% during the two highest insulin and proinsulin doses, respectively. Proinsulin had a significantly weaker effect than insulin, at the lowest infusion dose, in percent suppression of plasma nonesterified fatty acids, blood glycerol, and beta-hydroxybutyrate levels (all P less than 0.05). Blood lactate levels were lower during the P1 (628 +/- 43 microM) and P2 (657 +/- 93 microM) infusions compared with I1 (776 +/- 60 microM) and I2 (878 +/- 44 microM; P less than 0.05, P less than 0.02), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636699 TI - Mechanism of delayed hepatic glycogen synthesis after an oral galactose load vs. an oral glucose load in adult rats. AB - We have compared the effects of administration of oral galactose or glucose (1 g/kg) to 24-h fasted rats to examine the mechanism by which galactose regulates its own incorporation into liver glycogen in vivo. Liver glycogen increased to a maximum more slowly after galactose than after glucose administration (0.14 vs. 0.29 mumol.g liver-1.min-1). Glycogen accumulation after the galactose load was 70% of that after the glucose load (149 vs. 214 mumol), and the net increase in liver glycogen represented the same proportion (24 vs. 22%) of added carbohydrate after urinary loss of galactose was accounted for. Slower glycogen accumulation after galactose vs. glucose loading could not be explained by galactosuria, by differences in the active forms of synthase or phosphorylase, by end product (glycogen) inhibition of synthase phosphatase, or by different concentrations of the known allosteric effectors of synthase R plus I and phosphorylase a. Similar increases in glucose 6-phosphate were observed after both hexoses. AMP and ADP increased only transiently after galactose administration, and ATP, UTP, and Pi concentrations were unchanged. The UDP-glucose concentration decreased, whereas the UDP-galactose concentration increased two- to threefold after galactose but not glucose administration. The UDP-glucose pyrophosphorylase reaction is inhibited competitively by UDP-galactose. This could explain the decreased UDP glucose concentration and the reduced rate of glycogen synthesis after galactose was given. PMID- 1636700 TI - Comparison of indirect calorimetry and a new breath 13C/12C ratio method during strenuous exercise. AB - A new stable isotope method for the determination of substrate oxidation rates in vivo is described and compared with indirect calorimetry at rest and during high intensity exercise (30 min at 80-85% maximal O2 uptake capacity) in six well trained cyclists. This method uses the absolute ratios of 13C/12C in expired air, endogenous glucose, fat, and protein in addition to O2 consumption and is independent of CO2 production (VCO2). Carbohydrate and fat oxidation rates at rest, calculated by both methods, were not significantly different. During exercise the breath 13C/12C ratio increased and reached a steady state after 15 20 min. Carbohydrate oxidation rates during exercise were 39.4 +/- 5.2 and 41.7 +/- 5.7 mg.kg-1.min-1 [not significant (NS)], and fat oxidation rates were 7.3 +/ 1.3 and 6.9 +/- 1.2 mg.kg-1.min-1 (NS), using indirect calorimetry, and the breath ratio method, respectively. We conclude that the breath 13C/12C ratio method can be used to calculate substrate oxidation under different conditions, such as the basal state and exercise. In addition, the results obtained by this new method support the validity of the underlying assumption that indirect calorimetry regards VCO2 as a reflection of tissue CO2 production, during exercise in trained subjects, even up to 80-85% maximal O2 uptake. PMID- 1636701 TI - Effect of insulin on oxidative and nonoxidative pathways of free fatty acid metabolism in human obesity. AB - The dose-response relationship between the plasma insulin concentration and oxidative and nonoxidative pathways of free fatty acid (FFA) metabolism was examined in 11 obese and 7 lean subjects using a stepwise insulin clamp technique in combination with indirect calorimetry and infusion of [1-14C]palmitate. The fasting plasma FFA concentration was elevated in obese subjects (793 +/- 43 vs. 642 +/- 39 mumol/l; P less than 0.01) and was associated with an increased basal rate of plasma FFA turnover, FFA oxidation, and nonoxidative FFA disposal, i.e., reesterification (all P less than 0.01). Suppression of plasma FFA turnover by physiological increments in plasma insulin was impaired in obese compared with lean subjects. However, plasma FFA turnover expressed per kilogram fat mass was normally suppressed by insulin in obese subjects. Although insulin suppressed plasma FFA oxidation to the same extent in lean and obese subjects, inhibition of total lipid oxidation by insulin was impaired in the obese group. Obese subjects had an enhanced basal rate of nonoxidative FFA disposal, which was suppressed less by physiological increments in plasma insulin compared with lean controls. Therefore, we conclude that 1) lipolysis in uncomplicated obesity is normally sensitive to insulin; the enhanced FFA flux is simply a consequence of the increased fat mass. 2) Nonoxidative FFA disposal expressed per lean body mass is enhanced in obese subjects and correlates with the increase in plasma FFA concentration and fat mass. 3) Enhanced oxidation of intracellular lipids contributes to the enhanced rate of total lipid oxidation in obese subjects. PMID- 1636702 TI - Multiple cold air exposures change oral triiodothyronine kinetics in normal men. AB - The influence of cold exposure on triiodothyronine (T3) kinetics was studied in 16 men before, during (biweekly), and after 80 (10/wk) cold (4 degrees C) air exposures. We used serum values before and up to 24 h after a pharmacological oral (o) dose of T3 [76.8 nmol (50 micrograms)] to calculate noncompartmental kinetic parameters. To assess the role of thyroxine (T4) and thyrotropin (TSH), we administered a replacement dose of T3 [46.0 nmol/day (30 micrograms)] to eight men (+T3 group) and placebo to eight others (-T3 group) for the 2-mo study. There was no group effect of T3 treatment (+T3) on oral total volume of distribution (TVdo), metabolic clearance rate (MCRo), or disposal rate (DRo). TVdo was not changed over the study. Cold increased MCRo by 5.4 +/- 2.0 l.day-1.m-2. DRo increased with cold by 10.2 +/- 4.4 nmol.day-1.m-2. Although serum TSH, total T4, and free T4 decreased by approximately 50% in the +T3 group, the changes in MCRo and DRo with cold were not different from those in -T3. We describe that human T3 kinetics are changed with brief repeated exposures to cold air and that these increases in MCRo and DRo do not appear to be dependent on TSH or T4. PMID- 1636703 TI - Effects of fish and safflower oil feeding on subcellular glucose transporter distributions in rat adipocytes. AB - Effects of fish oil feeding on glucose transport systems and cell size in rat adipocytes were examined and compared with those of safflower oil or carbohydrate feeding under isoenergy intake conditions. Glucose transport activity was assessed by measuring 3-O-methyl-D-glucose transport. The concentration of erythrocyte type glucose transporter (GLUT-1) and muscle/fat type transporter (GLUT-4) was measured by immunoblotting. The amount of each transporter in intact cells was estimated by the amount of transporter and protein of each membrane fraction and by the recovery of marker enzymes. In cells from safflower-fed rats compared with those from carbohydrate-fed rats, insulin-stimulated glucose transport activity per cell decreased to 51% after a 1-wk feeding, and cell size increase became larger with these effects and continued for at least 4 wk. At 1 wk of feeding, GLUT-1 and GLUT-4 per cell in plasma membrane from insulin-treated cells decreased to 62 and 35%, respectively, with concomitant transporter decreases in the low-density microsome fraction. In cells from high-fish oil-fed rats in which two-thirds of safflower oil was replaced by fish oil, when compared with those from safflower oil-fed rats, insulin-stimulated glucose transport activity increased 1.7-fold after 1 wk of feeding with concomitant cellular GLUT 1 and GLUT-4 increases, but its effect declined thereafter. Parallel with this time course, cell size increase was smaller after 1 wk, but this effect also declined thereafter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636704 TI - Duodenal intramural nerves in control of pyloric motility and gastric emptying. AB - We have investigated the role of ascending duodenal intramural nerves in the control of isolated pyloric pressure waves (IPPW) and liquid gastric emptying. In six pigs, the proximal duodenum was transected to interrupt intramural nerves. A further six pigs had a sham operation. Four weeks after operation, motility of the antrum, pylorus, and duodenum was recorded by side holes and a sleeve sensor. Gastric emptying of a 1,000-ml test meal was significantly more rapid in duodenum transected animals (P less than 0.0001) during intraduodenal infusion of each of isosmolar dextrose (424 ml emptied), fatty acid (335 ml), and amino acids (396 ml) than in duodenum-intact animals (dextrose: 128 ml; fatty acid: 57 ml; amino acids: 192 ml). Associated with this, in duodenum-transected animals infusion of each of isosmolar dextrose, fatty acid, amino acids, and hyperosmolar saline failed to produce the stimulation of IPPW seen in duodenum-intact animals. In both duodenum-intact and -transected animals, supramaximal stimulation by intraduodenal infusion of 25% dextrose slowed gastric emptying and stimulated IPPW. Ascending duodenal intramural nerves are a major physiological pathway for nutrient- and osmolar-stimulated feedback control of pyloric motility and gastric emptying. PMID- 1636705 TI - Cholecystokinin at physiological levels evokes pancreatic enzyme secretion via a cholinergic pathway. AB - The mechanism by which physiological concentrations of cholecystokinin (CCK) evoke pancreatic exocrine secretion in humans was investigated. CCK octapeptide (CCK-8) dose dependently increased trypsin and lipase output in healthy humans. Atropine inhibited CCK-8 (10 ng.kg-1.h-1)-stimulated trypsin output by 84.0 +/- 7.7% and lipase output by 78.6 +/- 9.2%. The inhibition with atropine was much less with a CCK-8 dose of 40 ng.kg-1.h-1 (41.8 +/- 6.6% for trypsin and 46.3 +/- 7.3% for lipase). CCK-8 at 10 ng.kg-1.h-1 produced plasma CCK levels similar to postprandial levels (6.0 +/- 1.3 vs. 6.9 +/- 0.8 pM), whereas the 40-ng.kg-1.h-1 dose produced supraphysiological levels (18.4 +/- 3.1 pM). To evaluate if CCK might act via stimulation of cholinergic nerves, in vitro studies were performed using rat pancreas. CCK-8 (10 nM-10 microM) stimulated [3H]acetylcholine release from pancreatic lobules that was blocked by tetrodotoxin, a calcium-free medium, and the CCK antagonist L364,718. In conclusion, CCK-stimulated pancreatic enzyme secretion is dependent on cholinergic neural and noncholinergic pathways. In humans, CCK infusions, which produce plasma CCK levels similar to those seen postprandially, stimulate the pancreas predominantly via a pathway dependent on cholinergic innervation. Correlative in vitro experiments suggest that CCK may act by stimulation of neural acetylcholine release. In contrast, supraphysiological CCK infusions act in part via noncholinergic pathways. PMID- 1636706 TI - Stimulation of intramural secretory reflex by luminal distension pressure in rat distal colon. AB - The effects of distension on epithelial transport were examined by increasing intraluminal pressure in the rat distal colon in vitro. Two kinds of preparation, one with the musculature intact (intact preparation) and the other with the musculature and the myenteric neurons detached (mucosa-submucosa preparation), were used and the transmural potential difference (PD) changes were measured. In the intact preparation, distension with a luminal pressure of 15 cmH2O for 15 s caused a transient increase in PD (the lumen being more negative) of 3.7 +/- 0.6 mV. The distension-induced increase in PD was largely sustained when the pressure was applied for 10 min. Distension caused by intraluminal pressure, if it is of a similar degree to that caused by fecal pellets, is enough to elicit a PD increase. The distension-induced PD increase was largely abolished by the removal of Cl- from the bathing solution, or by the addition of furosemide or bumetanide. In the mucosa-submucosa preparation, distension with a luminal pressure of 15 cmH2O for 15 s caused an increase in PD of 5.8 +/- 0.6 mV. The distension-induced increase in PD was partially inhibited by atropine and was further decreased in the presence of tetrodotoxin both in the intact and mucosa-submucosa preparation. Indomethacin reduced the distension-induced PD increase in both preparations. These results suggest that distension by increased intraluminal pressure elicits the activation of Cl- secretion, which is mediated by submucosal plexus neurons. In addition, this distension-induced reflex is likely to be activated by normal fecal pellets. PMID- 1636707 TI - Role of chloride ions in lower esophageal sphincter tone and relaxation. AB - Studies were performed in strips of opossum lower esophageal sphincter (LES) muscle in vitro. External Cl(-)-free Krebs solution (0[Cl-]o) inhibited resting tone. Treatment with the Cl- channel blocker diphenylamine-2-carboxylate (DPC, 0.3-100 microM) caused a concentration-dependent relaxation of LES muscle, as did treatment with 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS, 1 microM 3 mM), a Cl(-)-HCO3- exchange blocker, and bumetanide (0.3-100 microM), a blocker of the Na(+)-K(+)-2Cl- cotransport. DIDS and bumetanide are also known to cause Cl- channel block. The calculated pD2 and Emax values for DPC, DIDS, and bumetanide were 5.24 +/- 0.28 (n = 5), 3.38 +/- 0.16 (n = 5), and 4.49 +/- 0.23 M (n = 5), and 78.80 +/- 5.38, 74.80 +/- 6.54, and 83.70 +/- 10.20%, respectively. The neuronal Cl- channel activators gamma-aminobutyric acid and glycine had no effect on the resting tone. DPC, DIDS, and bumetanide appear to have acted directly on smooth muscle rather than indirectly through the release of inhibitory neurotransmitters because LES relaxation by these agents was not influenced by tetrodotoxin (10 microM), which blocks action potentials in nerves, or by omega-conotoxin (1 microM), which inhibits the release of neurotransmitters from nerve terminals. LES muscle relaxed by exposure to 0[Cl-]o, DPC, DIDS, and bumetanide contracted with the addition of carbachol (30 microM); muscle so treated was resistant to the inhibitory neurotransmitter-mediated relaxation ordinarily induced by electrical field stimulation (EFS, 0.12-32 Hz). This effect was not nonselective, as the EFS-resistant muscle relaxed fully with isoproterenol (0.1-100 microM). HCO(3-)-free Krebs in the nominal absence of CO2 did not affect the resting tone and its relaxation. The Ca2+ channel blocker nifedipine decreased resting tone but did not antagonize the relaxation of carbachol-contracted muscle induced by either EFS or isoproterenol. These studies suggest that Cl- may play an important role in LES tone and relaxation due to inhibitory neurotransmitter released from intramural nerves. PMID- 1636708 TI - Neurohormonal mechanism of pancreatic exocrine secretion stimulated by sodium oleate and L-tryptophan in dogs. AB - In the present investigation, we have studied the effect of atropine on the pancreatic secretion stimulated by intraduodenal administration of either sodium oleate or exogenous cholecystokinin (CCK). In four dogs prepared with gastric and Thomas duodenal cannulas, pancreatic juice was collected for measurement of volume, bicarbonate, and protein output, and peripheral venous blood samples were obtained for radioimmunoassay of both secretin and CCK. Volume, bicarbonate, and protein output of the pancreatic juice increased significantly in response to sodium oleate (1-4 mmol/h) in a dose-dependent manner. The increase in pancreatic secretion paralleled the increments in both plasma CCK and secretin. Atropine given intravenously suppressed completely both pancreatic secretion and release of CCK stimulated by sodium oleate, whereas the release of secretin was not affected. Pancreatic secretion was significantly increased in a dose-dependent manner by exogenous CCK octapeptide (CCK-8) at 16, 32, and 64 micrograms (14, 28, and 56 pmol).kg-1.h-1. Atropine inhibited protein output only partially, but it did not influence bicarbonate output. In five additional dogs, the effect of atropine on L-tryptophan-stimulated pancreatic secretion was studied. Interestingly, atropine failed to influence the CCK release and pancreatic secretion of volume and bicarbonate, except for protein secretion, which was significantly inhibited. It was shown previously that atropine inhibited significantly the pancreatic secretion of bicarbonate stimulated by secretin in physiological doses. Thus we conclude that the inhibition by atropine of the pancreatic exocrine secretion stimulated by sodium oleate is mediated by both suppression of CCK release and inhibition of action of secretin on the exocrine pancreas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636709 TI - Pregnancy- and lactation-induced changes in active intestinal calcium transport in rats. AB - A time course study of active Ca transport in the duodenum and the terminal ileum was conducted using the everted gut sac technique during the last week of pregnancy and throughout lactation. A triphasic pattern was revealed in the proximal duodenum: a marked rise between 18 and 20 days of pregnancy, a plateau maintained during the last 3 days of pregnancy and the first 2-3 days of lactation, and a fall by day 4 of lactation. The late-pregnancy rise was significant also when expressed as milligrams Ca transported relative to tissue weight, indicating that intestinal hypertrophy was not the cause of the increase. The ratio of serosal to mucosal Ca concentration remained low until approximately day 11 of lactation, when it rose toward a new peak. There was no active Ca transport in the ileum until the third week of lactation. Serum prolactin levels increased 10-fold between 18 and 20 days of pregnancy and remained high until at least day 7 of lactation, but did not correlate significantly with duodenal Ca transport. Injected rat prolactin did not result in a precocious rise in Ca transport in pregnant rats. The fluctuations in duodenal Ca transport during lactation were reflected by a small, but statistically significant, decrease in net fractional Ca absorption at 6-9 days compared with either 2-4 days or 13-16 days. We suggest that duodenal active Ca transport plays only a small role in total intestinal Ca absorption in the lactating rat except when dietary Ca is greatly restricted. PMID- 1636710 TI - Chloride-mediated inhibitory junction potentials in opossum esophageal circular smooth muscle. PMID- 1636711 TI - Evidence for Kupffer cell migration along liver sinusoids, from high-resolution in vivo microscopy. AB - Kupffer cells are generally considered fixed tissue macrophages of the liver. However, we have evidence that this opinion is incorrect. High-resolution in vivo video microscopy shows that Kupffer cells have the ability to migrate along sinusoidal walls. Images recorded from anesthetized mice show active locomotion of cells with or against the direction of blood flow or in the absence of flow. The size, changing morphology, and uptake of carbon or microspheres strongly suggest that these are Kupffer cells. Quantitative measurements were made on 29 migrating Kupffer cells. The mean speed of migration was 4.6 +/- 2.6 (SD) microns/min and was not significantly different whether migration occurred with or against the flow. When fluorescent microspheres were given in vivo as a phagocytic challenge, Kupffer cells containing few microspheres migrated more slowly (0.9 +/- 0.9 microns/min, n = 10), whereas those containing many microspheres were never seen to migrate. Individual Kupffer cells were able to move independently, i.e., in directions different from those of neighboring Kupffer cells. These findings may have major implications for the role of Kupffer cells in scavenging foreign particles and as antigen-presenting cells. PMID- 1636712 TI - Effect of erythromycin on gastric myoelectrical activity in normal human subjects. AB - While a great deal of attention has been paid to the effect of erythromycin (Ery) on gastric contractility, its effect on gastric myoelectrical activity, which controls gastric motility, remains unknown. In this study, Ery (6 mg/kg) was infused intravenously in 14 normal human subjects (placebo controlled). Gastric myoelectrical activity was recorded using the surface electrogastrographic method. The electrogastrogram (EGG) recordings were analyzed using spectral analysis methods. It was found that the presence of the 2-4 cycles/min activity (normal slow wave frequency range) in the EGG was 51 +/- 19% in the first hour of the intravenous Ery infusion, which was significantly smaller (P less than 0.001, t test) than that (72 +/- 20%) during the corresponding control period (intravenous saline). This difference was, however, not quite significant (P = 0.067, t test) in the second hour after the infusions. The average score for nausea during Ery was 4.5 (0 for no nausea, 10 for the most severe nausea). We conclude that 1) intravenous Ery induces irregularities in the cutaneous EGG in normal human subjects; and 2) the noninvasive cutaneous EGG is an attractive method both for the investigation of the effects of pharmacological and prokinetic agents such as Ery on gastric myoelectrical activity in humans and for correlating clinical responses to changes in the EGG. PMID- 1636713 TI - Peptidergic nerves mediate post-nerve stimulation hyperemia in rat gut. AB - Cessation of perivascular nerve stimulation (NS) elicits a transient increase in intestinal blood flow above the prestimulatory value. This enhancement of blood flow constitutes the phenomenon of post-nerve stimulation hyperemia (PSH). We investigated the involvement of peptidergic sensory nerves in intestinal PSH. In anesthetized rats the velocity of blood flowing through the anterior mesenteric artery (VBF) was measured with a pulsed Doppler velocimeter. PSH was induced by 4 min of postganglionic electrical NS (5 Hz). PSH was abolished by distal periarterial application of tetrodotoxin and intra-arterial lidocaine, which suggests a peripheral sensory nervous mechanism for PSH. The increase in conductance at peak PSH was blocked by pretreatment with the selective, primary afferent neurotoxin capsaicin administered as 1) subcutaneous injection in neonatal life, 2) topical application to periarterial nerves, or 3) injection into the jejunal lumen. In rats pretreated with reserpine, NS evoked a hyperemic response, which was blocked by capsaicin. Treatment with adenosine deaminase inhibited PSH considerably less than capsaicin, suggesting a lesser role for adenosine in PSH. Our findings support the hypothesis that postganglionic NS activates both adrenergic and peptidergic nerves and that the latter release vasodilator peptides in the gut during PSH. PMID- 1636714 TI - Differential alterations in microvascular perfusion in various organs during early and late sepsis. AB - Although cellular dysfunction occurs very early in sepsis, it remains controversial whether this is solely due to a decrease in tissue perfusion. Recent studies have indicated that while active hepatocellular function was depressed, hepatic surface microvascular blood flow (MBF) increased in early sepsis but decreased in late sepsis as produced by cecal ligation and puncture (CLP). However, it is not known whether microvascular hyperperfusion in early sepsis and microvascular hypoperfusion in late sepsis are common events in other organs under such conditions. To study this, rats were subjected to sepsis by CLP, after which these and the corresponding shams received 3 ml/100 g body wt normal saline. Microvascular perfusion and MBF in various tissues were assessed by colloidal carbon infusion and laser-Doppler flowmetry, respectively, at 5 h (i.e., early sepsis) or 20 h (late sepsis) after CLP or sham operation. Carbon perfused areas were quantitated by an Optomax image analyzer. The results indicate that the carbon-perfused areas and MBF in the liver, renal cortex, spleen, and small intestinal serosa (only MBF) increased significantly 5 h after CLP. In late sepsis, however, the carbon-perfused areas and MBF were found to be significantly decreased. A highly linear relationship was observed between the changes of carbon-perfused areas and MBF during sepsis in the tested organs. Thus the microvascular responses in the fluid-resuscitated sepsis model are characterized by hyperperfusion in the early stage and hypoperfusion in the late stage of sepsis in the tested tissues. The cellular dysfunctions observed during the early stage of sepsis are, therefore, not due to any reduction in tissue perfusion. PMID- 1636715 TI - ATP induces two cholecystokinin binding affinity states in permeabilized rat pancreatic acini. AB - The influence of adenine and guanine nucleotides on cholecystokinin (CCK) receptor binding was examined in streptolysin O-permeabilized rat pancreatic acini. Specific binding of tracer to intact acini was 12.1 +/- 0.4% per milligram protein, while permeabilized acini bound 34.6 +/- 2.9% (n = 7). The increase in binding was also seen when normalized to DNA. Binding to permeabilized acini was reduced by the presence of 1 mM ATP to 23.0 +/- 1.3%. Analysis of competitive inhibition of tracer binding by unlabeled CCK-8 was consistent with binding to two affinity states on intact acini, with the equilibrium dissociation constants for the high (KdH)- and low (KdL)-affinity states equal to 41 +/- 5 pM and 5.2 +/ 0.4 nM, respectively; permeabilized acini displayed a single binding site with Kd = 598 +/- 40 pM. In the presence of 1 mM ATP, two states were seen on permeabilized acini with KdH = 85 +/- 11 pM and KdL = 2.7 +/- 0.6 nM. ATP, ATP gamma S, GTP, and GTP gamma S all inhibited binding, with half-maximal inhibition occurring at greater than 1 mM, 21 microM, 5 microM, and 0.4 microM, respectively. GTP gamma S (1 microM) also induced two affinity states with KdH = 112 +/- 7 pM and KdL = 1.5 +/- 0.2 nM (n = 3). Binding of CCK to pancreatic membranes was also decreased by ATP, and a similar regeneration of two binding affinity states was observed. ATP also decreased binding of [125I-Tyr4]bombesin to permeabilized acini, but in contrast did not generate two measurable binding affinity states.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636717 TI - Enhanced sinusoidal glutathione efflux during endotoxin-induced oxidant stress in vivo. AB - Hepatic release of reduced glutathione (GSH) and its oxidation [glutathione disulfide (GSSG) formation] were investigated in male Fischer rats in vivo after administration of various doses (1-15 mg/kg) of endotoxin (Salmonella enteritidis). Endotoxin dose dependently enhanced basal plasma glutathione (9.64 +/- 0.80 microM) and GSSG (1.08 +/- 0.23 microM GSH equivalents) levels by up to 450 and 1,300%, respectively, 60 min after administration of the highest dose. Determination of arteriovenous differences of plasma glutathione and portal vein blood flow demonstrated an increase of basal sinusoidal glutathione efflux (18 nmol.min-1.g liver wt-1) by 300% 15 min after 5 mg/kg endotoxin. Activation of Kupffer cells by retinol enhanced endotoxin-induced release of GSH and its oxidation severalfold. Endotoxin enhanced plasma levels of catecholamines; however, only an epinephrine-induced not the endotoxin-induced stimulation of hepatic GSH efflux was inhibited by adrenergic blockers. Depletion of serum complement by cobra venom factor pretreatment completely abolished the endotoxin induced increase of GSH release and enhanced GSSG formation. Zymosan-activated serum (source of C5a) increased GSSG formation and GSH release. It is concluded that endotoxin triggered an extracellular oxidant stress and an increased release of hepatic GSH indirectly through complement activation. Increased sinusoidal efflux of GSH and its extracellular oxidation may act as a local defense mechanism against the potentially deleterious effects of reactive oxygen generated by Kupffer cells during their physiological functions. PMID- 1636716 TI - Increased lymphatic flux of hyaluronan from cat intestine during fat absorption. AB - During fat absorption, chylomicrons with sizes up to 5,000-10,000 A must traverse an interstitium that has estimated pore sizes of 120-200 A to reach the lacteals. The present experiments were performed to study the behavior of the interstitial matrix component hyaluronan during fat absorption from the intestine. Ileal segments were isolated and autoperfused in pentobarbital-anesthetized cats. A postnodal lymphatic was cannulated, and lymph flow, protein, and hyaluronan concentration in lymph were determined. In group 1, a mixture of oleic acid and taurocholate was infused into the ileal lumen, while in group 2 the animals were fed cream overnight. In group 1, control lymph flow and hyaluronan concentration averaged 53.3 +/- 16.0 (SD) microliters.min-1.100 g intestine-1 and 21.4 +/- 16.0 micrograms/ml, respectively. Administration of taurocholate and oleic acid increased lymph flow and lymph hyaluronan concentration by 100 and 50%, respectively, resulting in a nearly three-fold increase in hyaluronan flux. Subsequent increases in venous pressure increased lymph flow and reduced hyaluronan concentration in lymph to less than 3 micrograms/ml. Hyaluronan flux remained approximately 2 micrograms.min-1.100 g intestine-1 independent of lymph flow. In group 2, no lymph sample was available before administration of fat. Hyaluronan concentration at control venous pressure was 19.3 +/- 6.7 micrograms/ml and fell to 10 micrograms/ml at the highest lymph flow. Hyaluronan flux was approximately 10 micrograms.min-1.100 g intestine-1 at the highest lymph flow and venous pressure (P less than 0.05 compared with the same lymph flow in group 1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636718 TI - Gallbladder mucosal function: studies in absorption and secretion in humans and in dog gallbladder epithelium. AB - The gallbladder is conventionally regarded as an absorptive organ such that dilute hepatic bile is both stored and concentrated. We studied 35 patients who had recovered from a percutaneous transhepatic gallbladder drainage performed for acute cholecystitis. After an overnight fast, gallbladder bile was dark brown in color and had a wide scatter in the lipid composition. Two hours after a meal, the gallbladder bile was opalescent white in color and had the composition of an extracellular fluid. This phenomenon was uniformly observed in all 35 patients and was also consistently reproducible when five patients were repeatedly studied. We used normal dog gallbladder epithelial cell monolayers grown in culture and examined sodium flux. Control gallbladder cells absorbed sodium. When secretin (0.5-2.5 x 10(-7) M) was added, there was a prompt reversal of sodium flux, resulting in net secretion. We conclude that secretion is a physiological function of the gallbladder mucosa. After feeding, the neural and humoral factors divert stored and newly secreted bile into the duodenum and induce active de novo secretion thus producing a gallbladder bile that is opalescent white with no lipids. Our results also have important implications on the origin of the pathological "white bile," the pathogenesis and treatment of gallbladder sludge, as well as the kinetic analysis of compounds undergoing enterohepatic recirculation. PMID- 1636719 TI - Renal failure increases gastric mucosal blood flow and acid secretion in rats: role of endothelium-derived nitric oxide. AB - Because of the contradictory findings in clinical studies, and the complete lack of animal studies, the purpose of this investigation was to characterize the changes in gastric mucosal blood flow (GMBF) and acid secretion in an animal model of chronic renal failure. Rats with chronic renal failure induced by partial kidney infarction had a significantly higher basal GMBF and lower gastric vascular resistance than control rats. The gastric acid secretory and mucosal hyperemic response to pentagastrin were markedly enhanced in renal failure rats. Because endothelial-derived nitric oxide (NO) is an endogenous vasodilator that regulates gastric vascular tone, we hypothesized that NO mediates the gastric hyperemia of renal failure rats. The administration of N omega-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of NO formation, produced a significantly greater decrease in GMBF in renal failure rats than in control rats, including a low dose inhibiting the basal hyperemia in renal failure rats but having no effect in control rats. It also attenuated pentagastrin-stimulated GMBF in both groups. In contrast, L-NAME produced a similar decrease in basal skeletal muscle blood flow in both renal failure and control rats. We conclude that in the renal failure rat 1) there is an increased basal GMBF and pentagastrin-stimulated acid output and GMBF, and 2) this gastric mucosal hyperemia is mediated by NO. PMID- 1636720 TI - Uptake of biotin by isolated rat liver mitochondria. AB - This study examined the mechanism of biotin uptake by liver mitochondria. Mitochondria were isolated from rat liver by an established procedure and demonstrated normal respiratory control ratios. Uptake of biotin with time at incubation buffer pH 6.1 was rapid and linear and occurred with a distinct "overshoot" phenomenon that peaked at approximately 1 min of incubation. At incubation buffer pH 7.4, however, uptake of biotin with time was significantly slower and no overshoot was observed. Gradual lowering of incubation buffer pH from 7.9 to 6.1 caused a similar pattern of increase in uptake of low (0.024 microM) and high (8 and 30 microM) concentrations of biotin. At incubation buffer pH 6.1 and 7.4, uptake of biotin as a function of concentration (0.012-30 microM) was linear and occurred at rates of 3.62 and 1.90 pmol.mg protein-1.5 s-1, respectively. Addition to the incubation medium of high concentrations of unlabeled biotin, its related compounds (biocytin, desthiobiotin, biotin methyl ester, thioctic acid, and thioctic amide), or substrates of known mitochondrial transporters (succinate, pyruvate, glutamate, malate, and phosphate) failed to cause any significant inhibition in uptake of [3H]biotin by mitochondria incubated in buffer pH 6.1 and 7.4. Furthermore, preloading mitochondria with unlabeled biotin, biocytin, malate, or aspartate failed to cause any significant stimulation in biotin uptake. At incubation buffer pH 6.1, treatment of mitochondria with the protonophore FCCP caused significant inhibition in pH dependent overshoot of biotin uptake. However, treatment of mitochondria with the potassium ionophore valinomycin caused significant stimulation in the pH dependent overshoot of biotin uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636721 TI - Submucosal reflexes: distension-evoked ion transport in the guinea pig distal colon. AB - Muscle-stripped segments of distal colon from guinea pigs were mounted in modified flux chambers to determine the effect of distension on mucosal secretion. Ion secretion was monitored as changes in short-circuit current (Isc). Distending forces were pressure gradients established by controlled reduction in liquid volume of the submucosal compartment of the chamber. Volume removal for 10 s or 5 min evoked a monophasic or biphasic increase in Isc, which returned to baseline within 5-20 min. The amplitude of the response correlated with the volume removed and was reduced by bumetanide and Cl-free solutions but not by tetraethylammonium or amiloride. Tetrodotoxin and atropine also suppressed the response. Neither the nicotinic receptor antagonist mecamylamine, the 5 hydroxytryptamine3 (5-HT3) receptor antagonist ICS 205-930, or the prostaglandin synthesis inhibitor piroxicam altered the response. Addition of prostaglandin D2 to the submucosal bath significantly enhanced the response. The results suggest that distension of the colon evokes anion secretion by activation of reflex circuits with cholinergic neurons and muscarinic synapses. Prostaglandins and 5 hydroxytryptamine acting at 5-HT3 receptors appear not to be signal substances in the reflex pathway, which evokes the secretory response to distension. PMID- 1636722 TI - Interleukin-1 alpha and -beta augment pulmonary artery transendothelial albumin flux in vitro. AB - Human recombinant interleukin-1 alpha (rIL-1 alpha) and -beta were studied to determine whether either could alter the permeability of bovine pulmonary artery endothelial cell monolayers. Endothelial cells were grown to confluence on filters mounted in chemotaxis chambers placed in wells. Barrier function of the monolayers was assessed by placing 14C-labeled bovine serum albumin ([14C]BSA) in the upper chamber and sampling the lower well for [14C]BSA. rIL-1 alpha induced a significant (P less than 0.01) dose- and time-dependent increase in transendothelial [14C]BSA flux. rIL-1 alpha exposures as brief as 30 min increased permeability, but the increased albumin transfer could not be demonstrated before 4 h after exposure. Exposures up to 6 h were reversible at 24 h. rIL-1 alpha induced significantly (P less than 0.01) greater increments in [14C]BSA flux than did equivalent exposures to rIL-1 beta. No important differences between bovine and human rIL-1 beta were demonstrated. Increased transendothelial flux could not be ascribed to either endothelial cytotoxicity or growth inhibition. There was no additive or synergistic relationship between rIL 1 alpha and human recombinant tumor necrosis factor-alpha. Our studies suggest that IL-1 alpha and -beta may play a role in the pathogenesis of pulmonary vascular leak. PMID- 1636723 TI - Bioassay of a tracheal smooth muscle-constricting factor released by respiratory epithelial cells. AB - Epithelium-derived factors of unknown identity have been proposed to modulate airway smooth muscle tone. We developed a novel sensitive bioassay system that allows serial perfusion of cultured respiratory epithelial cells and guinea pig trachea (GPT). GPT responses were assessed as diameter changes by computerized video microscopy (resolution, 15 microns). A permanent hamster lung epithelial cell line was grown on microcarrier beads and perfused in a cell column. When the outflow tubing from the epithelial cell column was connected to the inflow cannula, the detector GPT contracted, reaching 28 +/- 6% of the maximum methacholine (100 microM)-induced contraction (n = 12, P less than 0.001). Perfusion of the cell column with diclofenac (10 microM) or lysin-mono acetylsalicylic acid (100 microM) abolished the GPT contraction, whereas selective perfusion of the detector GPT with either agent did not block the contraction. Analysis of the effluent of the epithelial cell column demonstrated a significant basal release of prostaglandins F2 alpha and E2 (PGF2 alpha and PGE2) and 6-ketoprostaglandin F1 alpha, whereas only marginal amounts of thromboxane B2 were detected. When given exogenously, PGF2 alpha, PGE2, PGI2, and U-46619 all contracted the GPT. It is concluded that lung epithelial cells can contract GPT by releasing a transferable factor. This factor is likely to be a constrictor cyclooxygenase product that is not produced in epithelium-denuded GPT. PMID- 1636724 TI - Direct measurement of acetylcholine release in guinea pig trachea. AB - In this study, we applied high-performance liquid chromatography with electrochemical detection (HPLC-EC) to the measurement of acetylcholine (ACh) release from nerve endings in guinea pig tracheal smooth muscle. We also tested for muscarinic inhibitory regulation of ACh release in this species, which is widely used for studies of airway neural control. Clip-connected segments of the posterior membrane of the guinea pig trachea were mounted in organ baths between stimulating electrodes and incubated in Krebs-Henseleit buffer containing (in microM) 10 indomethacin, 1 neostigmine, 1 phentolamine, and 1 propranolol. To measure ACh, the bath was emptied and aliquots of buffer were injected directly into the HPLC-EC; the lower limit of detection was 1 pmol/200 microliters sample. Electrical field stimulation (EFS) at 5 Hz for 10 or 30 min increased ACh release from 1.8 +/- 1.4 (SE) to 6.2 +/- 1.3 pmol.mg protein-1.min-1 (n = 15). The effect of atropine was examined by comparing amounts of ACh released by EFS before and after exposure to either atropine (0.3 microM) or vehicle. Before atropine treatment, EFS-evoked ACh release was 4.9 +/- 0.6 pmol.mg protein-1.min-1; after atropine exposure, EFS-evoked release of ACh increased significantly to 15.0 +/- 2.2 pmol.mg protein-1.min-1 (n = 11; P less than 0.05). Corresponding values before and during exposure to vehicle were 9.3 +/- 4.4 and 10.7 +/- 4.7 pmol.mg protein-1.min-1, respectively. The ratios of the changes in EFS-evoked ACh release were 3.1 +/- 0.3 and 1.3 +/- 0.1 in atropine-treated and vehicle-treated groups, respectively (P less than 0.05). We conclude that HPLC-EC is a reliable and sensitive technique for the detection of EFS-evoked release of ACh from clip connected segments of guinea pig tracheal smooth muscle. PMID- 1636725 TI - In vitro responses of ovine intrapulmonary arteries and veins to endothelin-1. AB - We determined responses of third-generation intrapulmonary arteries and veins of fetal, newborn, and adult sheep to endothelin-1 (ET) and the role of endothelium and cyclooxygenase metabolites in ET effects in adult sheep lung vessels. Presence of endothelium in vessel rings was confirmed by response to endothelium dependent vasodilators, acetylcholine or bradykinin. Vessel tension induced by ET was expressed as a percentage of tension induced by 100 mM KCl. We found that arteries and veins contracted to 10(-9) to 10(-6) M ET in a dose-dependent manner. Veins exhibited greater sensitivity to ET than arteries in all age groups. Arteries and veins of adult sheep lungs were more sensitive to ET than those of fetal and newborn lambs. In adult sheep lung vessels, pretreatment with indomethacin (5 x 10(-6) M) and SQ 29548, a thromboxane A2-prostaglandin H2 receptor antagonist (10(-5) M), significantly attenuated venous contraction to ET; arterial contraction was unaffected. Denuding vessels of endothelium did not affect responses to ET. We conclude that, in ovine lungs, veins are more sensitive to ET than arteries and that developmental differences in pulmonary vascular responses to ET exist. PMID- 1636726 TI - IL-6 enhances TNF-alpha- and IL-1-induced increase of Mn superoxide dismutase mRNA and O2 tolerance. AB - Tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1), and interleukin-6 (IL-6) are multifunctional cytokines produced by a number of cells in response to endotoxin. We have previously demonstrated (M.-F. Tsan, J. E. White, T. A. Santana, and C. Y. Lee. J. Appl. Physiol. 68: 1211-1219, 1990, and M.-F. Tsan, C. Y. Lee, and J. E. White. J. Appl. Physiol. 71: 688-697, 1991) that tracheal insufflation of 5 micrograms of TNF-alpha or 1 microgram of IL-1 markedly protects rats against O2 toxicity and enhances pulmonary Mn superoxide dismutase (Mn SOD) activity. We now report that TNF-alpha and IL-1 at subprotective doses, e.g., 1 and 0.2 micrograms, respectively, act synergistically in protecting rats against O2 toxicity. Likewise, TNF-alpha and IL-1 at 0.005 microgram/ml each act synergistically in enhancing endothelial cell Mn SOD, but not Cu,Zn SOD mRNA levels. IL-6 at 5 or 10 micrograms provides no protective effect in rats against O2 toxicity and at up to 0.5 microgram/ml has no apparent effect on endothelial cell Mn or Cu,Zn SOD mRNA levels. However, IL-6 markedly enhances TNF-alpha- and IL-1-induced increases in Mn SOD mRNA levels and O2 tolerance. These results support an important role of Mn SOD in the protection against O2 toxicity. PMID- 1636727 TI - Restricted diffusion of macromolecules by endothelial monolayers and small-pore filters. AB - We studied the size-selective permeability and restricted diffusion (Rd) properties of macromolecules across bovine pulmonary artery endothelial cell (BPAEC) or epithelial (LLC-PK1) monolayers grown on polycarbonate (PC) filter supports using fluorescein isothiocyanate-hydroxyethyl starch (FITC-HES, 16 A less than ae less than 180 A). Most BPAEC seeded at subconfluent density and grown for 3-6 days produced barriers with marked Rd. This characteristic was similar to that measured across PC filters with pore radii (rp) of 150 and 250 A without cells. Rd of LLC-PK1 monolayers was consistent with a transport pathway rp of much less than 75A. BPAEC monolayers prepared by supraconfluent seeding showed convective solute transport due to a significant number of incompletely formed intracellular junctions. Most monolayers grown to confluence, or a thin layer of collagen type I prevented this effect, Rd was enhanced when BPAEC monolalyers were grown on this collagen network. These data suggest that the subendothelial layers, which includes basal lamina, pericyte, and interstitial collagen, may act as series resistors with the endothelium to provide the Rd observed in the microvascular wall in vivo. This may explain why BPAEC monolayers grown to confluence without subendothelial layers in vitro showed Rd consistent with large (150-250 A) rp that was significantly greater than those modeled as the small (approximately 50 A) "pore" or 6-A fiber matrix of the in vivo capillary wall. PMID- 1636728 TI - Formation of alveoli in rats: postnatal effect of prenatal dexamethasone. AB - We administered a glucocorticosteroid (dexamethasone) or its diluent to pregnant rats on gestation days 17, 18, and 19. In male offspring we determined the lung's gas exchange surface area (S(a)), the average volume (v) of gas exchange saccules at age 2 days and alveoli at age 14 days, and their number (N) on these days. S(a), v, and N at 2 days and v at 14 days were not affected by the prenatal administration of dexamethasone. However, S(a) and N were lower in 14-day-old pups from dexamethasone-treated dams than in pups from diluent-treated dams. In separate experiments we found the responsiveness to prenatal dexamethasone, as a depressor of the postnatal increase in S(a), appeared earlier in female than male fetuses; it was present in female but not in male fetuses on days 16-18 and was found in male fetuses on days 17-19. We conclude 1) prenatal administration of dexamethasone diminishes the postnatal increase in S(a), 2) responsiveness to this action of dexamethasone occurs earlier in gestation in female than in male fetuses, and 3) prenatal dexamethasone does not effect the postnatal volume of an average alveolus but diminishes their number in male pups. PMID- 1636729 TI - Stimulation of phosphatidylcholine hydrolysis in type II alveolar epithelial cells. AB - The effects of phorbol 12-myristate 13-acetate (TPA) or ATP on phosphatidylcholine (PC) hydrolysis were investigated in cultured type II pneumocytes prelabeled with [3H]choline or 1-O-[3H]octadecyl-sn-glycero-3 phosphocholine ([3H]lyso-PAF). In cells prelabeled with [3H]choline, TPA or ATP stimulated an increase in [3H]choline, [3H]phosphocholine, and [3H]glycerophosphocholine. The formation of these choline metabolites was associated with a concomitant loss of [3H]PC but not from disaturated PC or phosphatidylinositol. In cells prelabeled with [3H]lyso-PAF, the formation of [3H]phosphatidic acid (PA) and then [3H]1,2-DG was stimulated by TPA or ATP and was associated with a loss of 3H from PC but not from disaturated PC or phosphatidylinositol. There was a concentration-dependent formation of [3H]1,2-DG and [3H]PA in response to ATP. Downregulation of protein kinase C with TPA abolished the stimulation of PC hydrolysis. In addition to the generation of metabolites indicative of phospholipase C and/or D activity, [3H]lyso-PC, a product of phospholipase A2, was also generated in response to TPA. These findings suggest an important role for PC breakdown in signal transduction in type II pneumocytes. PMID- 1636730 TI - Surfactant protein D: subcellular localization in nonciliated bronchiolar epithelial cells. AB - Surfactant protein D (SP-D, CP4) is a collagenous surfactant-associated carbohydrate binding protein that was initially characterized as a biosynthetic product of type II pneumocytes. Immunoperoxidase studies of formaldehyde solution fixed and paraffin-embedded rat lung demonstrated staining for SP-D in the cytoplasm of a subpopulation of bronchiolar epithelial cells as well as type II cells. Accordingly, immunogold-labeling techniques were used to further examine the cellular distribution and subcellular localization of SP-D in the small airways. Lung tissues were fixed with 0.5% glutaraldehyde-3% paraformaldehyde and embedded in LR White resin. Sections were reacted with affinity purified polyclonal antibodies to SP-D, and sites of antibody binding were demonstrated using a biotinylated secondary antibody-streptavidin-gold detection system. Anti SP-D selectively decorated secretory compartments of nonciliated bronchiolar cells (Clara cells) with strong and specific labeling of apical electron-dense secretory granules. Almost all of the granules in nonciliated columnar cells were labeled; however, labeling was typically nonuniform, with preferential decoration of the periphery of the granule. The largest numbers of immunoreactive epithelial cells were observed in the distal membranous bronchioles, with progressively smaller numbers of cells in more proximal bronchioles. There was no detectable labeling of cells lining the large cartilagenous airways or trachea. These studies provide evidence that SP-D is a secretory product of nonciliated bronchiolar cells. We suggest that Clara cell-derived SP-D is a component of bronchiolar lining material, consistent with our hypothesis that SP-D contributes to surfactant metabolism and/or host defense within small airways. PMID- 1636731 TI - Tobacco smoke releases performed mediators from canine mast cells and modulates prostaglandin production. AB - The role of an extract of tobacco smoke in activating mast cells was studied. With the use of isolated, canine mast cells as a model, we found that cigarette smoke solution (CSS) induced the release of the performed mediators histamine and tryptase from these cells in an energy- and temperature-dependent, non-cytotoxic manner. There was no requirement for extracellular calcium. Nicotine tartrate did not reproduce the effect of CSS. Interestingly, mast cells produced little prostaglandin D2 (PGD2) in response to the CSS, and there was a concentration related inhibition of calcium ionophore A23187-induced PGD2 synthesis. This suggests at least two mechanisms acting on the mast cell: tobacco smoke can directly activate mast cells to release performed mediators and can simultaneously inhibit prostaglandin production. These observations suggest a mechanism by which mast cells may participate in the bronchospastic and proinflammatory changes seen in the lungs and airways of smokers. PMID- 1636732 TI - Processing of surfactant protein B proprotein by a cathepsin D-like protease. AB - Surfactant protein B (SP-B) is a hydrophobic peptide of relative molecular weight (M(r)) = 8,000 that is associated with pulmonary surfactant phospholipids. SP-B is synthesized by the alveolar type II epithelial cell as a proprotein of M(r) = 42,000 which requires at least two proteolytic cleavages to generate the 79 residue mature SP-B peptide. We have previously reported that cleavage of the NH2 terminal propeptide, to generate a processing intermediate of M(r) = 25,000, occurs in close temporal approximation to secretion. In the present study we demonstrate that SP-B proprotein, isolated from stably transfected Chinese hamster ovary cells, is processed to M(r) = 25,000 by a crude type II cell membrane fraction but not by intact type II cells or type II cell conditioned media. In vitro processing of the proprotein by the type II cell membrane preparation resulted in release of a single peptide of M(r) = 16,000-17,000, which was detected by antiserum directed against antigenic epitopes in propeptide of the precursor. SP-B processing activity was extracted by Na2CO3 lysis of the type II cell membrane preparation, had a pH optimum of 5.0-6.0, and was inhibited by 10(-7) M pepstatin A, suggesting that the NH2-terminal peptide of the precursor is cleaved by an aspartyl protease. Consistent with this hypothesis, processing of SP-B by a crude type II cell membrane preparation was blocked by antiserum directed against the aspartyl protease cathepsin D; further, purified cathepsin D efficiently processed the SP-B precursor to M(r) = 25,000. Collectively these results suggest that cleavage of the NH2-terminal propeptide of the SP-B precursor is mediated by cathepsin D or a cathepsin D-like protease localized within the secretory pathway of the type II epithelial cell. PMID- 1636733 TI - Cloning and expression of an airway epithelial 12-lipoxygenase. PMID- 1636734 TI - Effects of endothelin on renal hemodynamics and tubuloglomerular feedback. AB - The effect of endothelin (ET)-1 infusion on renal hemodynamics and the tubuloglomerular feedback (TGF) mechanism was examined in rats. ET-1 reduced early proximal flow rate (EPFR) measured in the absence of distal flow from 28 +/ 1 to 23 +/- 1 nl/min at a subpressor dose (100 pmol.100 g body wt-1.h-1 iv) and from 27 +/- 2 to 19 +/- 2 nl/min at a pressor dose (200 pmol.100 g body wt-1.h 1). Reductions of EPFR induced by loop perfusion at 40 nl/min were 11 +/- 1 and 12 +/- 1 nl/min at the subpressor and pressor doses and were not different from controls. The stop-flow pressure response to loop perfusion was not altered by the pressor dose of ET-1. The subpressor dose of ET-1 increased renal vascular resistance (RVR) by 40% but left glomerular filtration rate (GFR) and urinary excretion of sodium (UNaV) unaltered. The pressor dose of ET-1 not only increased RVR by 140% and decreased GFR and renal plasma flow by 37 and 52%, but it increased UNaV proportional to the rise in blood pressure (r = 0.724, P less than 0.01). ET-1 is a potent renal vasoconstrictor and induces pressure natriuresis. ET-1 increases both pre- and postglomerular resistances but does not affect TGF response. PMID- 1636735 TI - Oligopeptides: mechanism of renal clearance depends on molecular structure. AB - We have investigated the relative contribution of hydrolysis, intact transport and urinary excretion to the renal clearance of Gly-Sar, Gly-Sar-Sar, and Gly-Gly Sar in fed and starved rats. The results obtained from isolated kidney perfusion studies are summarized as follows: 1) clearance was fastest for Gly-Gly-Sar and slowest for Gly-Sar-Sar, 2) urinary excretion of Gly-Sar-Sar exceeded that of Gly Gly-Sar or Gly-Sar, 3) there was accumulation of products of hydrolysis of Gly Gly-Sar in the perfusate but not of Gly-Sar or Gly-Sar-Sar, 4) isolated brush border and basolateral membranes of renal tubular cells lacked hydrolytic activity against Gly-Sar and Gly-Sar-Sar but possessed hydrolytic activity against Gly-Gly-Sar, 5) an excess amount of Gly-Sar-Sar reduced the rate of clearance of Gly-Gly-Sar by approximately 40% and significantly increased urinary excretion of this peptide, 6) the nonfiltering kidney cleared Gly-Gly-Sar at a rate which was 50% of that of the filtering kidney but did not clear Gly-Sar, and 7) starvation for 96 h was without a significant effect on the renal clearance of either Gly-Sar or Gly-Sar-Sar but significantly reduced the renal clearance of Gly-Gly-Sar and the brush-border membrane hydrolase activity against this peptide. We conclude that the molecular structure determines the affinity of oligopeptides for the membrane transport and hydrolytic systems, which, in turn, determines their efficiency for clearance by the kidney. PMID- 1636736 TI - Eicosanoids modulate apical Ca(2+)-dependent K+ channels in cultured rabbit principal cells. AB - Patch clamp technology was utilized to study the effects of apical phospholipase A2 (PLA2) metabolites on "maxi K" channels in the principal cell apical membrane of rabbit cortical collecting tubule (CCT) primary cultures (B. N. Ling, C. F. Hinton, and D. C. Eaton. Kidney Int. 40: 441-452, 1991). At resting membrane potential, this channel is quiescent in the cell-attached configuration. Apical application of the PLA2 agonist melittin (1 microgram/ml) for 10 min increased single-channel open probability (Po) from 0.0004 +/- 0.0010 to 0.11 +/- 0.05. Similarly, apical exposure to 50 microM arachidonic acid (AA) or 0.5 microM prostaglandin (PG) E2, but not 0.5 microM PGF2 alpha, also increased channel activity. Conversely, 10 microM of the PLA2 antagonist quinacrine applied apically decreased Po. Removal of apical bath Ca2+ did not prevent melittin-, AA , or PGE2-induced channel activation. We then examined the role of maxi K channels and eicosanoids in principal cell volume regulation. Within seconds of reducing basolateral bath tonicity (285 to 214 mosmol/kgH2O), NPo (i.e., no. of channels x Po) initially increased approximately 200%, followed by a delayed but prolonged activation phase that was attenuated by removal of apical bath Ca2+. Pretreatment with 10 microM quinacrine, 100 microM indomethacin (cyclooxygenase inhibitor), or 0.25 microM thapsigargin (to deplete intracellular Ca2+ stores) abolished the initial phase of swelling-induced channel activation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636737 TI - Regulation of S6 kinase activity in renal proximal tubule. AB - The proximal tubule undergoes hypertrophy in response to loss of functioning renal mass and hyperplasia following injury by ischemia or nephrotoxins. Both hypertrophic growth and cell proliferation are characterized by increases in the rate of protein synthesis. To investigate regulation of protein synthesis in mammalian proximal tubule cells, potential peptide mediators of proximal tubule growth, epidermal growth factor (EGF) and angiotensin II, were studied in cultured rabbit proximal tubule cells. Although only EGF stimulated DNA synthesis, both agonists stimulated protein synthesis. One potential regulatory mechanism of eukaryotic protein synthesis involves phosphorylation of ribosomal protein S6 by activation of a specific serine/threonine kinase (S6 kinase). Both EGF and angiotensin II stimulated S6 kinase activity and S6 phosphorylation. Phorbol 12-myristate 13-acetate was also found to activate S6 kinase, and 24 h of pretreatment to deplete protein kinase C inhibited subsequent S6 kinase activation by a high concentration (10(-6) M) of angiotensin II. To determine whether S6 kinase was also activated in the kidney in vivo, S6 kinase activity was examined after ablation of renal mass. Within 1 h after contralateral nephrectomy, S6 kinase activity increased in rat renal cortex. In summary, both EGF and angiotensin II stimulated protein synthesis and S6 kinase activity in cultured proximal tubule cells, and S6 kinase activity also increased in renal cortex after contralateral nephrectomy. PMID- 1636738 TI - Hormonal regulation of rat renal proximal tubule brush-border membrane ionic permeability. AB - The effects on ionic permeability of toxins and hormones that activate or deactivate the guanine nucleotide regulatory (G) proteins that govern adenylate cyclase activity were examined in rat renal proximal tubule cell brush-border membranes. These studies demonstrate that activation of stimulatory G (Gs) proteins by cholera toxin or parathyroid hormone and deactivation of inhibitory (G (Gi) proteins by pertussis toxin result in a selective increase in Cl- permeability relative to that of K+ as determined with the potential-sensitive fluorescent probe 3,3'-dipropylthiadicarbocyanine iodide [diS-C3-(5)]. In contrast, activation of Gi by angiotensin II significantly decreases relative Cl- permeability. The selective increase in relative Cl- permeability induced by parathyroid hormone results in an inside-negative potential in membrane vesicles exposed to an inward NaCl gradient that is of sufficient magnitude to stimulate electrogenic, Na(+)-dependent glucose transport. These data suggest that the relative ionic permeabilities of brush-border membranes are tonically regulated by the opposing effects of hormones that act via Gs or Gi proteins. Changes in membrane potential resulting from this regulation may play an important role in modifying transport in the proximal tubule. PMID- 1636739 TI - Bidirectional peritoneal transport of immunoglobulin in rats: tissue concentration profiles. AB - Protein transport occurs between the blood and the peritoneal cavity during clinical procedures, but events within the surrounding tissue space are poorly understood. We used quantitative autoradiography to examine the tissue concentration profiles of immunoglobulin G (IgG) in regions surrounding the peritoneal cavity. We have varied the route of administration (intravenous or intraperitoneal), the osmolality of the dialysis solution (isotonic or hypertonic), and the time of analysis (20 or 200 min). After intravenous injection, IgG profiles were relatively flat in most tissues and were not affected by time or osmolality. Concentrations corresponded to the capillary density in specific tissues. After intraperitoneal administration, the IgG tissue profiles were significantly steeper than after intravenous administration. The tissue concentrations increased with time but decreased when a hypertonic solution was substituted for an isotonic solution. Hypertonic dialysis causes a water flux into the cavity, which dilutes the contents but does not prevent penetration of protein into the surrounding tissue. Based on IgG movement in tissue during hypertonic dialysis, the peritoneum appears to function as a heterogeneous structure, which allows osmotically induced water transport into the cavity in some regions with simultaneous transport of hydrostatic pressure driven water and solute flow from the cavity into the tissue in other regions. PMID- 1636740 TI - Increased functional differentiation of rabbit proximal tubule cells cultured in glucose-free media. AB - We have determined the influence of glucose (Glc)-free medium on the growth and differentiation of rabbit kidney proximal tubule cells (PTC) in primary cultures. The specific growth rates and the protein-to-volume ratios are shown to be independent of the culture conditions. In contrast, the functional expression of four brush-border membrane enzyme markers was found to decline steadily and in the same way from day 3 in culture up to late confluence in Glc-containing medium, and different evolution patterns and high expression levels were observed up to confluence in a Glc-free glutamine (Gln)-supplemented medium. Electron microscopy clearly showed, however, that the functional and morphological differentiation of the brush-border membrane is not correlated. Finally, by use of an indirect immunofluorescent technique in combination with flow cytometry, it is demonstrated that confluent cells grown in Glc and Gln media form homogeneous cell populations of PTC. It is thus concluded that the functional differentiation of rabbit kidney PTC in primary cultures is strongly dependent upon the energy source present in the culture medium. PMID- 1636741 TI - Sites of antinatriuretic action of insulin along rat nephron. AB - This study was aimed at identifying the renal sites of the antinatriuretic action of insulin by evaluating whether this hormone may alter the function of Na-K ATPase in specific nephron segments. For this purpose, possible actions of insulin on the rate of 86Rb uptake were evaluated in vitro on single segments of proximal convoluted tubule (PCT), thick ascending limb, and collecting tubule microdissected from collagenase-treated kidneys of normal rats. Results indicate that physiological concentrations of insulin inhibited by 44% the initial rate of ouabain-sensitive 86Rb uptake in the medullary and cortical thick ascending limb, whereas it increased it by 40% in proximal tubules and by 60% in both cortical and medullary collecting tubules. The kinetics and dose dependence of insulin actions were different in the thick ascending limb, the PCT, and the collecting tubule, with the latter less sensitive but displaying an earlier response to insulin than the PCT and the thick ascending limb. PMID- 1636742 TI - Effects of glucagon on glomerular filtration rate and urea and water excretion. AB - Clearance experiments were performed in anesthetized male Wistar rats to reevaluate the renal effects of glucagon (Gluc) on glomerular filtration rate (GFR) and solute and water excretion. After an 80-min control period, these effects were evaluated in the last 80 min of a 2-h intravenous Gluc infusion. Gluc induced significant increases in GFR (+20%), urine flow rate (+150%), free water reabsorption (+50%), urea synthesis and urea excretion (+66%), and nonurea solute excretion (+67%). In addition, fractional urea excretion (FEurea) increased by 43% (P less than 0.01). Additional experiments showed that increases in either urea excretion or urine flow rate (induced by appropriate infusion of urea or half-dilute saline), similar to those seen after Gluc, could not account for the increased FEurea. All significant effects of Gluc were also observed during infusion of antidiuretic hormone or during water diuresis. The tubular effects of Gluc could be explained by a reduction in proximal reabsorption. The dose of Gluc required to induce all the effects described above was 12 ng.min 1.100 g body wt-1, a dose producing an approximately 10-fold supraphysiological peripheral plasma concentration but a "physiological" level for the liver. Infusion of 1.2 ng induced almost no change in renal function, and infusion of 120 ng induced no greater effects than 12 ng. These results suggest 1) that Gluc, a hormone liberated after protein ingestion, exerts coordinated effects on liver and kidney to increase simultaneously urea synthesis and excretion and to promote water conservation and 2) that these effects could, at least in part, be indirect and depend on the Gluc-induced stimulation of hepatocyte metabolism. PMID- 1636743 TI - Effects of formate and oxalate on volume absorption in rat proximal tubule. AB - We examined the effects of formate and oxalate on the rate of fluid absorption (Jv) in the rat proximal convoluted tubule in situ. Proximal tubules were microperfused with a high-Cl-, low-HCO3- Ringer solution (pH 6.7), and the peritubular capillaries were perfused with a standard Ringer solution (pH 7.4), simulating conditions in the late proximal tubule. Jv, a measure of transtubular NaCl absorption under these conditions, was calculated from the change in luminal [3H]inulin. Addition of formate in the physiological range (500 microM) to the luminal perfusate increased Jv by 45%; addition of 500 microM formate to both luminal and capillary perfusates increased Jv by 57%. Similarly, addition of oxalate in the physiological range (5 microM) to the luminal perfusate increased Jv by 37%; addition of 5 microM oxalate to both luminal and capillary perfusates increased Jv by 57%. The stimulatory effects of formate and oxalate perfused in the lumen and capillaries were not additive. Addition of 4,4' diisothiocyanostilbene-2,2'-disulfonate (DIDS, 0.1 mM) to the luminal perfusate had no effect on baseline Jv measured in the absence of added formate and oxalate but completely abolished the increment in Jv induced by formate and oxalate. Addition of the Cl(-)-channel blocker diphenylamine-2-carboxylate (DPC, 0.2 mM) to the capillary perfusate had no effect on baseline Jv but completely abolished the increment in Jv induced by formate and oxalate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636744 TI - Effect of selenium-deficient diet in experimental glomerular disease. AB - We examined the effect of a selenium-deficient diet on two experimental models of glomerular disease, the puromycin aminonucleoside (PAN)-induced nephrotic syndrome, a model of minimal change disease, and passive Heymann nephritis, a complement-dependent and neutrophil-independent model that resembles membranous nephropathy. The specific activity of selenium-dependent glutathione peroxidase was markedly reduced in the liver, the kidney cortex, and in glomeruli in weanling male Sprague-Dawley rats placed on a selenium-deficient diet for 6 wk compared with rats fed a selenium-replete diet, with no significant differences in the specific activities of superoxide dismutase or catalase. PAN-injected selenium-deficient rats had a marked and significantly greater proteinuria throughout the course of the experiment compared with PAN-injected selenium replete rats with no significant histological differences. In the passive Heymann nephritis model induced by injecting anti-Fx1A immunoglobulin G, rats fed a selenium-deficient diet had significantly higher urinary protein (day 5: 91 +/- 16 mg/24 h, n = 10) compared with rats fed a selenium-replete diet (52 +/- 5 mg/24 h, n = 11) with no differences in the amount of antibody deposited in the kidney. The most likely explanation for the effect of a selenium-deficient diet is that selenium deficiency resulted in a marked reduction of glutathione peroxidase, thus indicating an important role of glutathione peroxidase in these models of glomerular injury. PMID- 1636745 TI - Functional and structural characterization of endosomes from toad bladder epithelial cells. AB - Previous functional studies of toad bladder endosomes have been complicated by the presence of multiple endosome subpopulations each possessing different permeability characteristics. To identify and characterize both water channel containing vesicles (WCV) and other endosome subpopulations, we combined flow cytometry, electron microscopy, stop-flow fluorometry, and sodium dodecyl sulfate polyacrylamide gel electrophoresis. Flow cytometry of endosomes identified distinct populations of fluorescein-labeled endosomes in bladders after removal of antidiuretic hormone (ADH) stimulation (ADH withdrawal). Centrifugation separated the larger fluorescein-labeled vesicles, sedimenting at lower speed (intermediate pellet, IP), from the smaller fluorescein-labeled vesicles, sedimenting at high speed (high-speed pellet, HSP). Permeability and structural studies of these subpopulations revealed the following. 1) IP endosomes labeled 10 min after ADH withdrawal (ADH IP) represented a highly purified population of WCV with high water permeability (Pf) that exhibited a low-activation energy and sensitivity to organic mercurials. 2) IP endosomes from unstimulated bladders did not contain functional water channels. 3) HSP from either ADH withdrawal or unstimulated bladders exhibited low Pf and acidified after addition of extravesicular ATP; moreover, protein compositions of purified HSP were distinct from those of purified IP. These results suggest that HSPs represent constitutive and not ADH-sensitive endosomes. 4) High permeability to protons (PH+) was seen in ADH IP endosomes but not the other fractions, providing strong evidence that the ADH water channel conducts protons. 5) Multivesicular bodies (MVB) exhibited low Pf and PH+, indicating that they do not possess functional water channels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636746 TI - Renal kinin antagonism does not impair pressure-induced natriuresis. AB - We studied the contribution of the renal kallikrein-kinin system to short-term electrolyte and water balance during baseline and during acutely elevated renal perfusion pressure (RPP) in the anesthetized dog. Renal blood flow, glomerular filtration rate, urine flow rate, renin secretion rate, and urinary excretion of sodium, potassium, prostaglandin E2 (PGE2), and kinins were measured at baseline RPP during intrarenal infusion of 0.9% saline or the competitive bradykinin analogue [D-Arg0,Hyp3,Thi5,D-Phe7,Thi8]bradykinin (50 micrograms/min), which blocks vascular and interstitial kinin receptors. RPP was then raised above baseline (control group 25%; kinin analogue group 22%) by ligating the celiac artery, the superior mesenteric artery, and the aorta distal to the renal arteries. Renal parameters were again measured during infusion of saline or the kinin analogue. The analogue had no effect on renal hemodynamic or excretory parameters at baseline perfusion pressures. Increasing RPP significantly increased urine flow rates and urinary sodium excretion rates (control group, 43 mumol/min; kinin analogue group, 55 mumol/min) in both groups of animals. Increasing pressure also tended to decrease renin secretion rate in both groups of animals; however, neither increased pressure nor infusion of the analogue affected urinary excretion of PGE2 or kinins. The results suggest that intrarenal kinins are not powerful short-term regulators of electrolyte and water balance and that an intact kallikrein-kinin system is not necessary to induce pressure diuresis and natriuresis. PMID- 1636747 TI - Regulation of mesangial cell cyclooxygenase synthesis by cytokines and glucocorticoids. AB - The cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF), potently induce prostaglandin formation in glomerular mesangial cells. Mechanisms by which these cytokines stimulate prostaglandin formation vary among cell types. We investigated whether alterations in phospholipase A2 (PLA2) or cyclooxygenase (COX) mass and activity contribute to the changes in mesangial cell prostaglandin production. These cytokines induced COX activity and mass in a time-dependent manner, which paralleled prostaglandin production. IL-1 increased COX mass approximately threefold by 24 h. TNF had a much smaller effect, although it appeared to be additive with IL-1. IL-1-induced COX mass was maintained at an increased level for at least 48 h. The glucocorticoid dexamethasone (DEX) virtually abolished prostaglandin production and blocked cytokine induction of COX activity and mass. DEX did not reduce COX activity or mass below the basal, serum-fed levels, however. By utilizing stable isotope methods, we could demonstrate that IL-1 increased free arachidonate levels, implying new PLA2 synthesis over a time course that was maximal at 6 h and was cycloheximide and actinomycin D sensitive. These data demonstrate that the cytokines IL-1 and TNF enhance synthesis of COX and PLA2, contributing to increased prostaglandin production. Cytokine-stimulated prostaglandin production ceases when cells are also treated with DEX, although control levels of COX activity and mass remain. This occurs because DEX inhibits the IL-1-induced enhanced arachidonate release. PMID- 1636748 TI - Intracellular recording and dye transfer in arterioles during blood flow control. AB - We tested for dye coupling between arteriolar smooth muscle cells (SMC) and endothelial cells (EC) and investigated the correspondence of vasomotor activity with changes in the membrane potential (Vm) of EC and SMC during blood flow control. Female golden hamsters (n = 8, 90-170 g) were anesthetized (pentobarbital sodium, 60 mg/kg ip). A cheek pouch was spread over an optical pedestal, transilluminated, and irrigated with physiological saline solution (37 degrees C, pH 7.4). Glass microelectrodes were filled with 3 M KCl or with Lucifer yellow dye (LY, mol wt 470; 106 mM). SMC or EC of arterioles (ID, 20-50 microns) containing blood flow were impaled under a stereomicroscope. Vm was similar [-48 +/- 3 and -52 +/- 4 mV (means +/- SE)] with KCl (n = 6) or LY (n = 13) microelectrodes, respectively. Acetylcholine (5 x 10(-6) M) increased Vm from -47 +/- 3 to -67 +/- 4 mV (n = 5; P less than 0.01) concomitant with vasodilation. Spontaneous slow waves in Vm (2/min, 15-30 mV) were observed in arterioles with vasomotion. In cells identified with LY microinjection, resting Vm was -52 +/- 8 and -44 +/- 2 mV for EC (n = 3) and SMC (n = 3), respectively. SMC injected with LY did not show evidence of dye transfer to other SMC or to EC. When an EC was injected, the dye spread to many contiguous EC but not to SMC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636750 TI - Effect of changing afterload and inotropic states on inner and outer ventricular wall thickening. AB - Effect of changing afterload and inotropic states on inner and outer ventricular wall thickening. Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H109-H116, 1992.- To study the differing behaviors of the inner (IH) and outer halves (OH) of the left ventricular (LV) free wall during an increasing afterload and changing inotropic states, we determined the LV pressure (LVP) and transmural (TM) and OH wall thickness (WTTM and WTOH) by sonomicrometry in 11 anesthetized dogs. The percent systolic wall thickening (% delta WT) and the fractional contribution (FC) were calculated. At rest, % delta WT of TM, IH, and OH were 22 +/- 1 (mean +/- SE), 33 +/- 3, and 13 +/- 2 (P less than 0.01 vs. IH), respectively. The FC of IH and OH were 74 +/- 5 and 29 +/- 4% (P less than 0.01 vs. IH), respectively. During increasing afterload by aortic constriction (AC) without drugs, % delta WT in IH was reduced to 22 +/- 2%, associated with unchanged % delta WT in OH (12 +/ 3%), whereas the FC of IH and OH were not altered from resting values. During AC with dobutamine infusion (3 micrograms.kg-1.min-1), the % delta WT and FC in each layer were not reduced from resting values. On the other hand, during AC with propranolol (2 mg bolus iv), the reduction of % delta WT in IH was greater (from 29 +/- 4 to 15 +/- 6%, P less than 0.01) than that in OH (from 11 +/- 2 to 10 +/- 3%; P less than 0.01 vs. IH). The FC in the IH was decreased (56 +/- 16%) by AC with propranolol, so that the difference in FC between IH and OH became insignificant (FCOH 40 +/- 13%, P greater than 0.1 vs. FCIH).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636749 TI - Modulation of NO and endothelin by chronic increases in blood flow in canine femoral arteries. AB - Experiments were designed to determine whether chronic increases in arterial blood flow alter production of or response to nitric oxide and endothelin. Canine femoral arteries proximal to an arteriovenous fistula- and from the contralateral sham-operated blood vessels were removed, cut into rings, and suspended for measurement of isometric force in organ chambers. The remainder of the artery was homogenized for measurement of endothelin content by radioimmunoassay. NG monomethyl-L-arginine (10(-4) M) caused concentration-dependent increases in tension only in fistula-operated arteries. Endothelium-dependent relaxations to acetylcholine and BHT-920 were greater in fistula- compared with sham-operated arteries. These differences were reduced by the arginine analogue. Pertussis toxin (100 ng/ml) inhibited relaxations to acetylcholine only in fistula-operated arteries and to BHT-920 only in sham-operated arteries. Contractions to endothelin-1 were greater in fistula- compared with sham-operated arteries. These results suggest that chronic increases in blood flow enhance the tonic and receptor-stimulated production of nitric oxide and its release by receptors coupled to pertussis toxin-sensitive guanine nucleotide regulatory proteins. Furthermore, chronic increases in blood flow may either inhibit the production of endothelin or promote its depletion from endothelial cells while simultaneously increasing the sensitivity of the smooth muscle to its contractile effects. PMID- 1636751 TI - Long-term coronary stenosis in rats: cardiac performance, myocardial morphology, and contractile protein enzyme activity. AB - To determine the effects of chronic nonocclusive coronary constriction on cardiac hemodynamics, myocardial structure, and contractile protein enzyme activity, the left coronary artery was narrowed in rats, and measurements of ventricular pump function, extent and localization of tissue damage, and myofibrillar Mg2+ and Ca2+ myosin adenosinetriphosphatase (ATPase) activities were measured 3 mo later. In the presence of coronary artery stenosis averaging 56%, two different degrees of depression in global cardiac performance were identified, and the animals were divided in two groups. In the first group, left ventricular end-diastolic pressure (LVEDP) was increased and LV+ and/or--the first derivative of LV pressure (dP/dt) were decreased, whereas in the second group end-diastolic and peak systolic LV pressures, LV+ and -dP/dt and right ventricular dynamics were all impaired. Thus left ventricular dysfunction and failure occurred with coronary narrowing. Structurally, multiple foci of replacement fibrosis were found across the left ventricular wall, but the number of these lesion profiles was 2.6-fold larger in failing animals than in rats with cardiac dysfunction. Biochemically, Mg(2+)-ATPase activity in myofibrils and Ca2+ myosin ATPase were not altered biventricularly. On the other hand, a shift from V1 to V3 myosin isoenzymic content occurred in the failing left ventricle. In conclusion, the late impairment in ventricular pump function associated with prolonged coronary artery stenosis appears to be sustained more by the magnitude of myocardial damage than by defects in contractile protein enzyme activity. PMID- 1636752 TI - Influence of pericardial constraint on atrioventricular interactions. AB - The effects of the pericardial constraint in control, tamponade, and absent pericardium conditions was studied in 18 anesthetized open-chest dogs. Atrial pressures and systolic and diastolic inflow volumes per beat in the superior (SVC), inferior vena cavae (IVC), and pulmonary vein (PV) were measured. With increasing tamponade, 1) the systolic-diastolic distribution of venous flow became almost exclusively systolic in the SVC (P less than 0.001) and IVC (P less than 0.05), as the gamma-descent disappeared; 2) similar but lesser left-sided changes occurred in PV flows (P less than 0.001) and pressure; and 3) the systolic-diastolic distribution of venous flow was modulated by heart rate. The results imply that during tamponade 1) increased pericardial liquid pressure associated with an increased pericardial constraint couples reciprocal atrial and ventricular volume changes; 2) the atria fill during ventricular ejection (atrioventricular interaction); 3) total heart volume must have been relatively constant throughout a cardiac cycle; and 4) differences in right and left heart compliances may explain persistent diastolic PV flow. Pericardiotomy produced a small increase in the ratio of diastolic to systolic venous inflow volumes (P less than 0.025), suggesting that normally the pericardium has a minor influence on atrioventricular interaction, the volume changes in the atria and ventricles being relatively uncoupled. With severe tamponade, a homogeneous pericardial fluid column tightly couples atrial and ventricular volume changes and accounts for the characteristic changes in atrial pressure waveforms and patterns of venous flow. PMID- 1636753 TI - Regional contractile performance during acute ischemia in porcine right ventricle. AB - Studies of regional ischemia in the canine left ventricle (LV) have shown augmented systolic segmental shortening in nonischemic regions. To characterize these responses in the right ventricle (RV), acute occlusions of the right coronary artery (RCAO) were produced in anesthetized pigs. Orthogonal pairs of ultrasonic segment-length crystals were implanted in the mid-RV free wall (ischemic region) and in the outflow tract (nonischemic region). RV pressure-area work loops were generated during inferior vena caval occlusions, and both slope (M) of the preload recruitable stroke work relationship and elastance (Ees) of the end-systolic pressure-area relationship were determined by linear regression. Under control conditions, there was no significant difference in M or Ees of the two regions. After RCAO, fractional area shortening decreased by 84% in the ischemic region but increased by 21% in the nonischemic region. Although RV end diastolic pressure and areas in both regions increased, M was significantly reduced by 78% only in the ischemic region. There was no change in contractile function in the nonischemic region as described by M and Ees despite the increase in systolic fractional area shortening. Therefore the nonischemic region of the porcine RV exhibits an apparent compensatory hyperkinesis in response to regional ischemia similar to that shown for the canine LV, consistent with the Frank Starling mechanism. PMID- 1636754 TI - Removal of sarcolemmal sialic acid residues results in a loss of sarcolemmal functioning and integrity. AB - Treatment of neonatal rat heart cells with neuraminidase results in a large increase of cellular-associated Ca2+. The study described below was designed to test the hypothesis that neuraminidase produces its effects by increasing the transient Ca2+ channel current, as proposed by Yee et al. (24). This ICa,T can be inactivated by dodecylsulfate (DDS) (17). The experimental data show that 1) the increase in cellular Ca2+ during neuraminidase treatment cannot be explained by an increased ICa,T; 2) neuraminidase treatment has a much more profound effect on sarcolemmal permeability than has been recognized previously; and 3) the effect of neuraminidase treatment can be prevented by 50 microM DDS. The study indicates that glycocalyx-lipid bilayer interactions are important in maintenance of selective permeability of the sarcolemma. The protective effect of 50 microM DDS is probably mediated by insertion of the negatively charged amphiphilic molecule in the sarcolemma, although the exact mechanism remains to be elucidated. PMID- 1636756 TI - Sodium and left ventricular mass in untreated hypertensive and normotensive subjects. AB - To determine whether urinary sodium excretion (a rather rough estimate of sodium intake) can influence left ventricular mass independently of arterial pressure, 91 untreated subjects with essential hypertension and 50 normotensive subjects of similar age were studied. Left ventricular mass index (M-mode echocardiography) was positively correlated with urinary sodium excretion in hypertensive (r = 0.22, P less than 0.01) as well as normotensive subjects (r = 0.22, P less than 0.05), and systolic arterial pressure was correlated only in hypertensive subjects (r = 0.23, P less than 0.01). When hypertensive subjects were divided into groups with appropriate or inappropriate left ventricular mass by reference to a theoretical optimal left ventricular mass for each subject's level of systolic arterial pressure, left ventricular mass was appropriate in 68% and inappropriate in 32% of subjects. Urinary sodium excretion was higher in subjects with inappropriate left ventricular mass compared with those with appropriate left ventricular mass. In conclusion, sodium excretion may be an important modulator of the influence of arterial pressure on the left ventricle in normotensive subjects and subjects with essential hypertension. PMID- 1636755 TI - Chemoreceptor responsiveness in fetal sheep. AB - Fetal peripheral chemoreceptor responses to arterial O2 saturation and changes in PCO2 have not yet been quantitated. In 24 late-term chronically instrumented fetal sheep, we measured the heart rate response to acute hypoxemia induced by uterine arterial occlusion at various resting O2 saturations (25-86%) and at induced reductions and increases in baseline O2 saturation. As an index of fetal chemoreceptor responsiveness we calculated the fall in heart rate divided by the fall in arterial O2 saturation (delta HR/delta sat). delta HR/delta sat was inversely related to resting O2 saturation at levels less than 65%, but greater than 65% this relationship was no longer present. However, an induced increase in baseline O2 saturation from 66 +/- 12 to 76 +/- 10% decreased delta HR/delta sat from 2.6 +/- 1.6 to 1.8 +/- 1.0, indicating that when resting O2 saturation is greater than 65% there may be adaptation of peripheral chemoreceptors. Below 65%, an induced decrease in baseline O2 saturation increased delta HR/delta sat (to 3.8 +/- 1.8), suggesting a lack of adaptation to lower O2 saturations. Concomitant changes in PCO2, or differences in baseline PCO2, did not affect delta HR/delta sat during uterine arterial occlusion, which suggests that there is no interdependence between O2 and CO2 as a stimulus for the fetal peripheral chemoreceptor. However, acute hypercapnia (n = 24 in 8 fetal sheep) induced bradycardia. Furthermore, this bradycardia was related to the increase in fetal arterial PCO2. We conclude that the fetal peripheral chemoreceptor is sensitive to hypoxemia and hypercapnia and that the hypoxemia response is accentuated with decreases in initial O2 saturation. PMID- 1636757 TI - Comparable sensitivity of flow contraction and relaxation to Na reduction may reflect flow-sensor characteristics. AB - Physiological salt solution infused through the lumen of a resistance branch of the rabbit central ear artery mounted in an isometric myograph causes both contraction and relaxation. The effect of reductions in extracellular Na up to 26 mM (20% of the NaCl content of the physiological saline solution) on these flow induced changes in wall force and on the contraction to norepinephrine (10(-6) M) and relaxation to acetylcholine (10(-8) to 3 x 10(-6) M) and papaverine (10(-6) to 3 x 10(-5) M) has been studied. Na in the physiological saline solution was reduced by substitution of NaCl with sucrose or N-methyl-D-glucamine. The effect of either of these substitutions was to reduce both responses, contraction and relaxation, to the same extent. This sensitivity is such that physiological changes in blood Na concentration would be expected to influence flow-induced changes in wall tone. Responses to norepinephrine, acetylcholine, and papaverine were not significantly changed by these alterations in Na. It is argued that since reduction of extracellular Na diminished both contraction and relaxation to a similar extent, leading to relaxation and contraction respectively, that this effect probably occurs at a site common to both flow responses. Because both flow effects occur after endothelium removal and the extracellular matrix binds a large proportion of the Na in the blood vessel wall, this may represent the location of a flow-sensitive mechanism. PMID- 1636758 TI - Uterine prostaglandin production in ovine pregnancy: effects of angiotensin II and indomethacin. AB - The ovine and human uteroplacental vascular beds are more refractory to angiotensin II (ANG II)-induced vasoconstriction than the systemic vasculature. ANG II increases in vitro prostacyclin (PGI2) production by uterine but not omental arteries from pregnant sheep. Thus vasodilator prostaglandins may account for this difference in vascular responsiveness. We measured uterine and systemic eicosanoid production and hemodynamic responses in pregnant sheep before and during intravenous ANG II (1.15 and 11.5 micrograms/min). ANG II caused dose related increases in arterial pressure and systemic and uterine vascular resistance (P less than 0.05). PGI2 metabolite (6-keto-PGF1 alpha) in the uterine vein rose from 166 +/- 70 (SE) to 223 +/- 114 and 631 +/- 323 pg/ml, respectively (P less than 0.05), and arterial levels increased from 67 +/- 24 to 145 +/- 78 and 312 +/- 173 pg/ml, respectively (P less than 0.05). Basal uterine venoarterial differences of 6-keto-PGF1 alpha were 99 +/- 43 pg/ml and increased during 11.5 micrograms ANG II/min to 295 +/- 181 pg/ml (P less than 0.05) but not during 1.15 micrograms/min (64 +/- 30 pg/ml). Responses were similar in gravid and nongravid uterine horns. Unilateral uterine prostaglandin inhibition with indomethacin did not alter basal uterine blood flow or systemic responses to ANG II (0.573-11.5 micrograms/min); however, ipsilateral uterine prostaglandin production fell and uterine vasoconstrictor responses increased (P less than 0.05). During ovine pregnancy ANG II increases uterine PGI2 production. PGI2 appears in part to attenuate ANG II-induced uterine vasoconstriction. PMID- 1636759 TI - An animal model of chronic coronary stenosis resulting in hibernating myocardium. AB - An experimental animal model of hibernating myocardium is presented. Sixteen animals were initially prepared of which seven were selected for final review. Hearts were instrumented in two separate surgical procedures such that maximum phasic flow velocity in the left anterior descending (LAD) coronary artery was reduced by 50% and followed over 1 wk. Regional shortening declined at 1 wk to 62% of aerobic values (P less than 0.048) and did not improve over 2 h reperfusion. Metabolic determinations, obtained after 1 wk of coronary stenosis and immediately sampled before and after release of the LAD flow constrictor, showed no evidence of acidosis, hypercarbia, or an inability to extract oxygen at the tissue level. Thereafter, during the 2-h reperfusion period, hearts were able to respond to dobutamine (10 micrograms/kg infusion over 1 min) challenge with an appropriate shift in an end-systolic length estimate of contractility. Mitochondrial respiration at the conclusion of the studies in the reperfused bed demonstrated near normal recovery compared with aerobic values. None of the seven hearts showed gross evidence of infarction and only one heart was noted to have a few microfocal changes of healing infarction. Thus a new model of coronary stenosis is presented, which affected substantial reductions in mechanical function consistent with the concepts of hibernating myocardium. These mechanical events were not associated with marked metabolic abnormalities, reflecting advanced ischemia or mitochondrial dysfunction and could be transiently improved with inotropic stimuli. This model may prove beneficial as a tool in understanding mechanistic events underlying the hibernating heart. PMID- 1636760 TI - Oxygen transport during anemic hypoxia in pigs: effects of digoxin on metabolism. AB - We tested whether digoxin would limit tissue hypoxia during severe anemia by improving peripheral O2 distribution or decreasing O2 demands. Hematocrit (Hct) was reduced in eight control and eight digoxin-treated pigs from 27-28% to 17-18, 11-12, and 7-8%. Whole body and hindlimb blood flow, O2 transport, O2 extraction, and O2 consumption and serum catecholamines (epinephrine and norepinephrine) were determined at each Hct. Arterial and femoral venous lactate and O2 deficit were obtained to reflect tissue hypoxia. Cardiac output was significantly greater (P less than 0.05) with digoxin, as expected, but there were no differences in hindlimb blood flow. Also, whole body and hindlimb O2 extractions were equal in both groups for similar levels of O2 transport, suggesting that digoxin did not alter the relationship of O2 flow to metabolism in regional circulations. As whole body O2 consumption fell, controls accumulated more (P less than 0.05) O2 deficit and arterial lactate than the digoxin group. Furthermore, the slope demonstrating the linear increase of lactate with respect to O2 deficit was much steeper in controls (y = 1.11 + 0.06x) than in digoxin (y = 1.36 + 0.02x), suggesting that there were differences in the degree of tissue hypoxia for comparable O2 deficit. This may be attributed to the marked differences in catecholamine response: epinephrine was higher in controls at Hct of 7-8% and norepinephrine was higher at Hcts of 11-12 and 7-8%. Digoxin may have inhibited the release of catecholamine or reduced the stimulus for catecholamine secretion during anemia. We speculate that digoxin markedly improved the balance between peripheral O2 supply and demand during anemia by inhibiting catecholamine thermogenesis, thereby decreasing O2 demands. This may explain some of the salutary effects of glycosides in high-output cardiac failure with normal ventricular function. PMID- 1636761 TI - Contribution of adenosine to isoproterenol-stimulated prostacyclin production in rabbit heart. AB - This study investigated adenosine's contribution to isoproterenol-stimulated prostacyclin production, measured as 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) output, and mechanical function in the isolated rabbit heart perfused with Krebs-Henseleit buffer. The isoproterenol-induced increase in 6-keto-PGF1 alpha was diminished by adenosine (10 microM), the A1 receptor antagonist 1,3-dipropyl, 8-cyclopentylxanthine (DPCPX 0.06 microM), and the A2 receptor agonist CGS-21680 (0.6 microM); CGS-21680 did not decrease heart rate (HR) or myocardial contractility (dP/dt(max)). The isoproterenol-induced increase in 6-keto-PGF1 alpha was potentiated by the A1 receptor agonist 1-deaza,2-chloro,N6 cyclopentyladenosine (DCCA, 0.6 microM) and the A2 receptor antagonist 3,7 dimethyl,1-propargylxanthine (DMPX, 6 microM). The isoproterenol-induced increase in dP/dt(max) and HR was diminished by adenosine, DCCA, and DMPX. DPCPX enhanced dP/dt(max) and HR and prevented the decrease by adenosine and DCCA of the isoproterenol-induced increase in HR and dP/dt(max); the increase by DCCA but not the decrease by adenosine in 6-keto-PGF1 alpha output was abolished. DMPX abolished the effect of adenosine and CGS-21680 to reduce isoproterenol stimulated 6-keto-PGF1 alpha. These data suggest that adenosine generated in response to isoproterenol attenuates its effect on HR and dP/dt(max) through A1 receptors and on prostacyclin synthesis via A2 receptors. PMID- 1636762 TI - Angiotensin II receptor antagonism in ovine heart failure: acute hemodynamic, hormonal, and renal effects. AB - The hemodynamic, hormonal, and renal effects of angiotensin II-type 1 receptor antagonism (AT1A) have not been documented previously in heart failure (HF) or compared with angiotensin-converting-enzyme inhibition (ACEI). Accordingly, we investigated the acute (2-h) response to losartan (1 and 10 mg/kg iv) or vehicle (N saline) followed by captopril (12.5 mg) on separate days in an ovine model of HF induced by 7 days of rapid ventricular pacing. Losartan induced a significant rise in plasma renin activity (PRA) and plasma angiotensin II levels (P less than 0.01 and P less than 0.001, respectively), in association with a fall in the plasma aldosterone-to-PRA ratio (P less than 0.001) and plasma atrial natriuretic peptide (P less than 0.05). Mean arterial and left atrial pressure both fell significantly after losartan (P less than 0.001), whereas the rise in cardiac output was not sustained. The response to captopril was similar except for plasma angiotensin II, which declined (P less than 0.001). Glomerular filtration and urine sodium excretion were maintained despite a fall in renal perfusion pressure. In conclusion, the vasodilatation and renal effects of AT1A were similar to ACEI. Thus AT1A may be a useful therapeutic alternative to ACEI in HF. PMID- 1636763 TI - Regulation of spontaneous EDRF release in diabetic rat aorta by oxygen free radicals. AB - The interaction of endothelium-derived relaxing factor (EDRF) and oxygen-derived free radicals may potentially play an important role in the pathophysiology of complications associated with diabetes. In the present study, we investigated spontaneous EDRF release in diabetic rat aorta that is unmasked by the addition of superoxide dismutase (SOD). SOD produced a significantly greater relaxation in diabetic aorta compared with control aorta using both aortic ring and bioassay preparations. This relaxation was unaltered by pretreatment with catalase or indomethacin. Removal of the endothelium or pretreatment with either NG monomethyl-L-arginine or methylene blue eliminated SOD-induced relaxation in both control and diabetic rings. Measurement of antioxidant enzymes revealed an elevation in catalase in diabetic aorta, with no difference in the SOD or glutathione peroxidase activity. The increase in catalase activity suggests increased exposure of diabetic aorta to hydrogen peroxide. Pretreatment of rings with the catalase inhibitor, 3-amino-1,2,4-triazole, attenuated the SOD-induced relaxation in diabetic aortic rings but had no effect in control aortic rings. In summary, our observations suggest that the diabetic rat aorta releases more spontaneous EDRF than control aorta; however, the activity of EDRF on vascular smooth muscle tone is masked by increased destruction by oxygen-derived free radicals. PMID- 1636764 TI - Left ventricular shape changes during the course of evolving heart failure. AB - The temporal relationship between left ventricular (LV) shape changes and the development of LV dysfunction, dilation, and sympathoadrenergic hyperactivity was examined in 10 dogs with chronic heart failure produced by multiple sequential intracoronary microembolizations. LV shape was quantitated from serial ventriculograms based on the ratio of the major to minor axis at end systole and end diastole. Measurements were made at baseline (before embolizations) and were repeated at 2, 8, and 16 wk after the last embolization. A significant increase of LV sphericity was present at 2 wk, with only minimal changes occurring thereafter. Despite the tendency for LV shape changes to plateau between 2 and 16 wk, LV ejection fraction continued to decline (31 +/- 1 vs. 20 +/- 2%; P less than 0.001), and LV end-diastolic volume continued to increase (86 +/- 6 vs. 103 +/- 9 ml; P less than 0.01) as did plasma norepinephrine concentration (456 +/- 30 vs. 868 +/- 172 pg/ml; P less than 0.02). These data indicate that in the course of evolving heart failure, LV shape abnormalities precede the development of profound LV dysfunction, dilation, and overt activation of the sympathetic nervous system. PMID- 1636765 TI - Cytosolic pH measurements in single cardiac myocytes using carboxy seminaphthorhodafluor-1. AB - This study examines the use of carboxy-seminaphthorhodafluor-1 (C-SNARF-1) as an indicator of cytosolic pH in isolated rat cardiac myocytes. The emission spectrum of C-SNARF-1 when excited at 530 nm contains two well-separated peaks at approximately 590 and 640 nm, corresponding to the acidic and basic forms of the indicator. This spectral feature allows the indicator to be used in the single excitation, dual emission ratio mode. When C-SNARF-1 is loaded into rat cardiac myocytes as the membrane permeant ester derivative, C-SNARF-1/AM, the indicator localizes within the cytosol with virtually no partitioning into the mitochondria. C-SNARF-1 does not load into isolated mitochondria in suspension. There was no evidence for the presence of non-deesterified C-SNARF-1 within the cells. C-SNARF-1 can be calibrated in situ using a technique that abolishes all transsarcolemmal pH gradients. A 0.7-unit shift in the apparent pK (pKapp = pK log10) between the in vitro calibration and the in situ calibration is consistent with a change in beta (I640 to pH 9/I640 at pH 5) in the cytosolic environment (beta in situ/beta in vitro = 0.21) and not a change in the true pK of the indicator. The contribution of cellular autofluorescence to the total signal can be made negligible. There is no effect of C-SNARF-1 on the contractile properties of rat cardiac myocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636766 TI - Laser-Doppler flowmetry in monitoring regulation of rapid microcirculatory changes in spinal cord. AB - We established a rabbit model for continuous on-line monitoring of spinal cord microcirculation using laser-Doppler flowmetry (LDF). We tested the suitability of this model for studying rapid, nonequilibrium microcirculatory blood flow (BF) states induced by pharmacological treatments, hemorrhage, and asphyxia. Effective BF regulation was observed at systemic arterial pressure levels of 50 mmHg. Autoregulatory vasodilation began 1 min after the onset of severe hypotension, whereas more immediate vasodilation took place after asphyxia (hypercarbia). Pathological situations were studied in a simple model of spinal cord (SC) ischemia-reperfusion after 10 (n = 7) and 25 min (n = 7) of ischemia and 2 h of reperfusion. After 25 min of ischemia, delayed hypoperfusion (BF -35 +/- 7%, P less than 0.01) took place in association with tissue edema. LDF offered sensitive, stable, and reproducible estimates of microcirculation with high temporal resolution, thus permitting on-line evaluation of rapid, nonequilibrium BF responses and delayed states of spinal cord BF dysregulation. PMID- 1636767 TI - A method to reconstruct myocardial sarcomere lengths and orientations at transmural sites in beating canine hearts. AB - The ability to measure cyclic changes in myocardial sarcomere lengths and orientations during cardiac ejection and filling would improve our understanding of how the cellular processes of contraction relate to the pumping of the whole heart. Previously, only postmortem sarcomere measurements were possible after arresting the heart in one state and fixing it for histology. By combining such histological measurements with direct observations of the deformation experienced by the same myocardial region while the heart was beating, we have developed a method to reconstruct sarcomere lengths and orientations throughout the cardiac cycle and at several transmural layers. A set of small (1 mm) radiopaque beads was implanted in approximately 1 cm3 of the left ventricular free wall. Using biplane cineradiography, we tracked the motion of these markers through various cardiac cycles. To quantify local myocardial deformation (as revealed by the relative motion of the markers), we calculated the local deformation gradient tensors. As the heart deforms, these describe how any short vectorial line segment alters its length and orientation relative to a reference state. Specifically, by choosing the reference state to be the arrested and fixed heart and by measuring the sarcomere vector in that state, we could then use the deformation gradient tensors to reconstruct the sarcomere vector that would exist in the beating heart. As ventricular chamber volume varied over its normal range of operation, the range of reconstructed sarcomere lengths (approximately 1.7-2.4 microns) was comparable to other histological studies and to measurements of sarcomere length in excised papillary muscles or trabeculae. The pattern of sarcomere length changes was markedly different, however, during ejection vs. filling. PMID- 1636768 TI - Isometric biaxial tension of smooth muscle in isolated cylindrical segments of rabbit arteries. AB - Biaxial tension developed in the common carotid and femoral arteries of rabbits by the activation of smooth muscle was determined in vitro using cylindrical segments. While the smooth muscle was stimulated with 10(-5) M norepinephrine, the intraluminal pressure and axial force were measured under isometric conditions, i.e., keeping the diameter and length constant. The development of the active tension in the axial direction was roughly proportional to that in the circumferential direction. The ratio of the axial stress response to the circumferential one was positively correlated to the ratio of the axial stretch to the circumferential one. The axial response was larger than expected from the histological observation that the smooth muscle cells align almost circumferentially. This means that although smooth muscle cells are oriented almost circumferentially, the extracellular matrix transmitted the smooth muscle constriction force not only in the circumferential direction, but also in the longitudinal direction under isometric conditions. PMID- 1636769 TI - How to encode arterial pressure into carotid sinus nerve to invoke natural baroreflex. AB - The purpose of this study was to develop an artificial baroreceptor that was capable of invoking the "natural" baroreflex by electrically stimulating the afferent nerve. In six anesthetized, vagotomized dogs, we first identified, using the white-noise method, the transfer function from carotid sinus pressure to aortic pressure (HCSP.AoP) and that from the electrical carotid sinus nerve stimulation to aortic pressure (HCSN.AoP). We then backcalculated the transfer function required for the artificial baroreceptor (HCSP.CSN) as the ratio of HCSP.AoP to HCSN.AoP. To activate the artificial baroreceptor, we electrically stimulated the carotid sinus nerve with the frequency-modulated pulse train obtained in real time by convolving the impulse response of HCSP.CSN with instantaneous aortic pressure. We tested performance of the artificial baroreceptor by imposing random changes in blood volume. The pressure-stabilizing effects of the artificial baroreceptor were indistinguishable from those of the native one. We conclude that the artificial baroreceptor can invoke the natural baroreflex. The proposed framework generally would be applicable to interface artificial devices with the central nervous system. PMID- 1636770 TI - Oxygen diffusion in hamster striated muscle: comparison of in vitro and near in vivo conditions. AB - To investigate the suggestion of A. S. Popel, R. N. Pittman, and M. L. Ellsworth [Am. J. Physiol. 256 (Heart Circ. Physiol. 25): H921-H924, 1989] that Krogh's diffusion coefficient for O2 in vivo might be an order of magnitude higher than in vitro, O2 diffusion coefficient (DO2) and resting O2 consumption were measured on hamster retractor muscle in vitro and under near in vivo conditions where the muscle remained attached to the animal but the arterial inflow was occluded just before measurement. Experiments were performed on two groups of animals, differing in weight and age. We found that DO2 determined in vitro (extrapolated to 37 degrees C) was 1.81 +/- 0.12 x 10(-5) cm2/s for group I (smaller and younger), which was not significantly different from the value (2.00 +/- 0.08 x 10(-5) cm2/s) determined in group II. In both groups, DO2 under near in vivo conditions tended to be 10-15% larger than the value in vitro, although this trend did not reach statistical significance. It is unlikely that this trend is large enough to reconcile the inconsistency between theoretical and experimental determinations of O2 diffusion from the arteriolar network of this tissue. PMID- 1636771 TI - Quantitation of specific binding of orosomucoid to cultured microvascular endothelium: role in capillary permeability. AB - Orosomucoid (also known as alpha 1-acid glycoprotein) is a highly sialylated, polyanionic serum glycoprotein. Its presence in vascular perfusates alters microvascular permeability, presumably by binding to the endothelial glycocalyx, but the rest of its functions remains unknown. In this study, we assess the binding of bovine serum orosomucoid (BSO) to the surface of bovine pulmonary microvascular endothelial cells (BLMVEC) in culture at 4 degrees C. The binding of radioiodinated BSO (125I-BSO) reached equilibrium after 10 min of incubation, was not calcium dependent, and was reversible by greater than 80% in 30 min. The binding of 125I-BSO was competed with unlabeled BSO but not by transferrin, immunoglobulin, gelatin, ovalbumin, mannan, fucoidan, mucin, or asialomucin. In addition, binding was not affected by the presence of galactose, glucose, fucose, mannose, N-acetyl-D-galactosamine, or N-acetyl-D-glucosamine. This binding behavior is not consistent with carbohydrate recognition by lectin-like molecules such as the asialoglycoprotein receptor. Scatchard analysis of the BSO binding to BLMVEC produced a concave-upward shaped curve, which revealed a higher affinity binding component with an apparent equilibrium affinity constant (Kd) of 8.6 nM and a maximum receptor number of 40,000/cell and revealed a moderate affinity component with a Kd of 9.1 microM with a maximum binding of 10(7) binding sites per cell. Other blood vessel-associated cells clearly bound less BSO with a lower binding affinity than the BLMVEC monolayers. From the binding data, we estimated the total increase in the negative charge of the glycocalyx with orosomucoid binding to be approximately 17 meq/l.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636772 TI - Comparison of norepinephrine and isoproterenol clearance in congestive heart failure. AB - Congestive heart failure (CHF) is accompanied by increased sympathetic nervous activity. Previous studies have demonstrated that plasma norepinephrine (NE), a marker of sympathetic nervous activity, is elevated in CHF due to increased NE spillover into the circulation and decreased NE clearance. In this study we compared the clearance of NE and isoproterenol (ISO) in eight CHF subjects (plasma NE 601 +/- 133 pg/ml), and in nine controls (plasma NE 285 +/- 53 pg/ml) by using steady-state infusions of tritiated NE ([3H]NE) and tritiated ISO ([3H]ISO). Because ISO is not a substrate of neuronal reuptake but is removed from the circulation in a way that is similar to NE after neuronal reuptake blockade with desipramine, ISO clearance may permit a gross estimation of non neuronal uptake of circulating NE. The NE clearance was lower in CHF than in the control group (CHF 1.25 +/- 0.13, controls 2.04 +/- 0.22 l.min-1.m-2; P = 0.009). The ISO clearance was reduced similarly in CHF (CHF 0.90 +/- 0.09, controls 1.59 +/- 0.12 l.min-1.m-2; P less than 0.001). Because the ratio of ISO to NE clearance was similar in both groups, our findings suggest that a low cardiac output in CHF decreases the availability of circulating catecholamines to tissue elimination sites. PMID- 1636773 TI - Altered agonist-induced Ca2+ mobilization in aortic smooth muscle cells from cardiomyopathic hamsters. AB - We compared the responses to the Ca(2+)-mobilizing effects of norepinephrine (NE), endothelin-1 (ET), and arginine vasopressin (AVP) of primary cultures of vascular smooth muscle cells (VSMCs) from aortas of young (30-40 days old) cardiomyopathic (Bio 14.6 strain) and age-matched control hamsters. In Bio 14.6 VSMCs, saturating concentrations of NE and ET elicited increases in the intracellular Ca2+ concentration ([Ca2+]i), which reached approximately 50 and 62% of those in control VSMCs. AVP elicited a significant increase in [Ca2+]i only in Bio 14.6 VSMCs. In contrast, 10 microM ionomycin induced similar Ca2+ responses in both types of cells in the absence of extracellular Ca2+. Ligand binding assay revealed that maximal binding values for alpha 1-adrenergic antagonists and ET in Bio 14.6 VSMCs were 59-64 and 85% of those in control VSMCs. Thus VSMCs from aortas of Bio 14.6 hamsters had reduced reactivity to NE and ET but increased response to AVP. The reduced Ca2+ response of Bio 14.6 VSMCs to NE appeared to be due mainly to a decrease in the receptor number. PMID- 1636774 TI - Role of endothelium-derived nitric oxide in myocardial reactive hyperemia. AB - In pentobarbital sodium-anesthetized dogs we investigated the role of the endothelium-derived nitric oxide and adenosine in the regulation of the coronary blood flow during myocardial reactive hyperemia. Repayments of flow debt after 10 , 20- and 60-s occlusion of the left circumflex coronary artery (LCX) were measured before and after infusion of NG-monomethyl-L-arginine (L-NMMA; n = 15), 8-phenyltheophylline (8-PT; n = 5), and both L-NMMA and 8-PT (n = 5) into the LCX. Infusion of L-NMMA (2 mumol/min, for 20 min) reduced repayments of flow debt after 10-, 20-, and 60-s LCX occlusion by 30 +/- 4 (P less than 0.01), 34 +/- 3 (P less than 0.01), and 14 +/- 3% (P less than 0.01), respectively. Infusion of 8 PT (0.75 mumol/min for 15 min) also reduced these repayments of flow debt by 31 +/- 7 (P less than 0.01), 30 +/- 7 (P less than 0.01), and 34 +/- 6% (P less than 0.01), respectively. Simultaneous infusion of L-NMMA and 8-PT significantly attenuated the peak reactive flow rate and reduced repayment of flow debt after 20-s LCX occlusion by 57 +/- 1% (P less than 0.001), and this reduction in repayment of flow debt was significantly greater than each of those by the individual administration of L-NMMA and 8-PT (both P less than 0.01). The suppressive effect of L-NMMA on repayment of flow debt after 20-s LCX occlusion was quickly reversed by the infusion of L-arginine (3 mg/min for 10 min; n = 5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636775 TI - Catecholamines in cerebrospinal fluid are increased by behavioral arousal and myocardial ischemia. AB - To study the central neural mechanisms involved in malignant ventricular arrhythmia, concentrations of norepinephrine in the cerebrospinal fluid were measured during behavioral stimulation and during coronary artery occlusion. Pigs were instrumented via thoracotomy with catheters to measure mean arterial pressure and plasma catecholamines and with silk snares around the left anterior descending coronary artery for occlusion after recovery from surgery. Cannulas were placed in the lateral ventricle of the brain to sample cerebrospinal fluid. Behavioral arousal was induced by lifting the pig in a canvas sling for 5 min. Mean arterial pressure, heart rate, and both plasma and cerebrospinal fluid norepinephrine concentrations increased significantly after lifting stimulation. In a separate experiment, 5 min after coronary artery occlusion, both plasma catecholamines and norepinephrine in cerebrospinal fluid were significantly elevated. Furthermore, pigs in which ventricular fibrillation occurred after occlusion had significantly higher concentrations of norepinephrine in cerebrospinal fluid before coronary artery occlusion. PMID- 1636776 TI - Effects of mechanical vibration on left ventricular diastolic properties during global ischemia. AB - To examine the effect of mechanical vibration on ventricular relaxation and diastolic chamber stiffness under global ischemia, we studied eight coronary perfused, isolated, isovolumic canine left ventricles (LV). To produce varying degrees of impaired relaxation, graded coronary flow reduction and paced tachycardia were imposed. A mechanical 50-Hz, 2-mm-amplitude vibration was applied during diastole and was turned off during systole. Without diastolic vibration, the relaxation time constant of LV pressure (tau) increased with the severity of ischemia. The chamber stiffness index (K) from the diastolic pressure volume relationship showed a slight increase during ischemia; tau decreased with diastolic vibration. The change in tau with vibration increased with ischemia and was dependent on vibration amplitude but not heart rate. The ratio of tau to the diastolic interval (DI, the time from peak negative rate of LV pressure change to end diastole) always decreased with vibration and was linearly correlated with K (r = 0.93; P less than 0.01). K decreased with vibration when tau/DI was greater than 0.3. We conclude that diastolic vibration improves impaired relaxation and chamber stiffness under myocardial ischemia. PMID- 1636777 TI - Suppression of baroreceptor discharge by endothelin at high carotid sinus pressure. AB - Endothelin is a potent vasoconstrictor peptide released from endothelial cells capable of producing marked and prolonged increases in arterial pressure. The purpose of this study was to determine whether endothelin alters the sensitivity of arterial baroreceptors. Multifiber baroreceptor activity was recorded from the vascularly isolated, endothelium-denuded carotid sinus in dogs anesthetized with alpha-chloralose. Local exposure of baroreceptors to endothelin at a concentration of 10(-8) M produced vasoconstriction of the carotid sinus as measured with sonomicrometer crystals but did not alter baroreceptor discharge significantly. A higher concentration of endothelin (10(-7) M) markedly suppressed baroreceptor activity, particularly at pressures greater than 100 mmHg (n = 7, P less than 0.05). The magnitude of the decrease in activity was dependent on the duration of exposure to endothelin. Baroreceptor activity measured at carotid pressures of 60, 100, and 200 mmHg averaged 23 +/- 4, 65 +/- 6, and 100 +/- 0% of maximum during control; 38 +/- 12, 61 +/- 9, and 74 +/- 15% after exposure to endothelin (10(-7) M) for 2 min; and 27 +/- 8, 53 +/- 12, and 56 +/- 19% after 12 min, respectively. The suppression of nerve activity with the high dose of endothelin was not accompanied by additional vasoconstriction, suggesting a direct effect of endothelin on nerve endings. We speculate that endothelin released from endothelial cells may act in a paracrine manner to suppress activity of baroreceptors, particularly at high levels of arterial pressure. Such an action would interfere with the buffering capacity of the baroreflex and promote hypertension. PMID- 1636778 TI - Anticipatory activity and entrainment of circadian rhythms in Syrian hamsters exposed to restricted palatable diets. AB - Activity rhythms were recorded from hamsters in three conditions: during timed feedings of an attractive diet with free access to regular food, during restriction to 70% of normal food consumption, and during moderate food deprivation with limited temporal access to an attractive diet. An attractive diet given to intact animals did not induce anticipatory activity or entrainment, but damage to the suprachiasmatic nuclei (SCN) led to the development of anticipatory activity. Food restriction to 70% of normal intake led to anticipatory components in some intact animals, without entraining the dominant circadian pacemaker. The combination of a palatable diet and food restriction led to anticipatory activity before the daily feeding times and entrainment of a previously free-running circadian rhythm in some animals. Ablation of the SCN did not eliminate anticipatory activity in experimental animals, but did eliminate the free-running component of the rhythms. These results indicate that hamsters have a mechanism separate from the SCN that can anticipate daily feeding times, as rats do, and that they may show entrainment of the SCN-based pacemaker to such feeding schedules. PMID- 1636779 TI - Behavioral effects of A71623, a highly selective CCK-A agonist tetrapeptide. AB - We studied the behavioral effects of a novel cholecystokinin tetrapeptide (CCK-4) analogue, A71623, with full agonist activity and high affinity and selectivity for the CCK-A receptor subtype relative to the CCK-B receptor. In tests for anorectic activity, A71623 was found to suppress 60-min intakes of a liquid diet in both deprived and sated rats, and the effects were blocked by a selective CCK A antagonist, A70104. Compared with CCK-8, A71623 was found to have improved potency and duration of action; the most potent route of administration was intraperitoneal. A71623 also suppressed the intake of a liquid diet and a 0.2 M sucrose solution in lean and obese Zucker rats. In daily injection studies, the anorectic activity of CCK-8 diminished rapidly, whereas the suppressant effects of A71623 on food intakes and body weight gains persisted throughout the 11-day treatment period. Finally, A71623 reduced the spontaneous locomotor activity of rats at doses above those required to suppress intakes. These studies are the first to describe the behavioral effects of a potent and highly selective CCK-A receptor agonist. PMID- 1636780 TI - Fractal properties in fetal breathing dynamics. AB - The dynamic pattern of fetal breathing was studied in 17 fetal lambs with chronically implanted electromyographic electrodes in the diaphragm. The instantaneous breathing rate time series appeared similar on different time scales, with clusters of faster breathing rates interspersed with periods of relative quiescience, suggesting self-similarity. Distribution histograms of the interbreath intervals (IBIs) showed log-normal distribution for IBIs less than 1 s and inverse power-law distribution for IBIs greater than 1 s. The ratio of log normal distribution to power-law distribution varied from approximately 2 at 102 days to approximately 30 by 130 days of gestation. Fast Fourier transform of the breathing rate time series revealed 1/f beta power spectra for all animals, with beta increasing linearly from 0.43 to 0.88 between 102 and 139 days. Studies in the newborn lamb showed further maturation in both the distribution characteristics of the IBIs, as well as in the 1/f power spectra, with beta approaching 1.0 at 2 days after birth. The inverse power-law relationship in the distribution of the IBIs, together with the 1/f beta power spectra, indicate scale invariance and suggest that fractal mechanisms are involved in the regulation of fetal breathing. PMID- 1636781 TI - Hyperosmolality impairs ammonia-mediated inflammation: implications for the renal medulla. AB - Although ammonia modifies the third component of complement (C3) and activates the alternative pathway, inflammation is not seen in the renal medulla where ammonia concentrations are normally elevated. We examined the effect of the unique hyperosmolar milieu of the renal medulla on the interaction of ammonia with C3 and the capacity of ammonia-modified C3 (NH3.C3) to induce cytolytic injury and stimulate neutrophils (PMN). Incubation of purified human C3 with ammonia in concentrations found in urine results in significant disruption of the C3 thiolester bond compared with ammonia-free controls. Coincubation with urinary osmolytes and hyperosmolar NaCl and urea does not impair thiolester disruption over a range of ammonia concentrations. However, hyperosmolar NaCl and urea virtually abolish cytolytic injury mediated by the alternative pathway. Coincubation with the organic osmolytes betaine, sorbitol, and inositol fails to reverse this inhibitory effect of hyperosmolar NaCl and urea. Hyperosmolar NaCl and urea also suppress lytic injury mediated by ammonia and complement in MDCK, a cell line derived from canine distal tubular epithelium. Both PMN degranulation and respiratory burst responses to NH3.C3 are significantly blunted in the presence of hyperosmolar NaCl and urea. Hyperosmolality also impairs PMN responses to the formyl peptide N-formyl-Met-Leu-Phe and phorbol 12-myristate 13 acetate (PMA). Therefore, in an in vitro setting of hyperosmolar NaCl and urea, amidation of C3 occurs, but subsequent membrane-directed and receptor-mediated functions of NH3.C3 are markedly impaired.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636782 TI - Healing of intestinal anastomoses in adrenalectomized rats given corticosterone. AB - To determine the effect of physiological variations in glucocorticoid levels on wound healing, adrenalectomized rats, implanted with corticosterone pellets of varying concentrations, and sham-operated rats were subjected to ileal transection followed by end-to-end anastomosis. Adrenalectomized animals with plasma corticosterone levels less than 2.5 micrograms/dl suffered 25% mortality. In rats surviving 1 wk, bursting pressure of the anastomotic site was measured as an index of wound healing. At plasma corticosterone levels of 3.9-7.4 micrograms/dl, which approximate normal physiological levels, bursting pressure was not significantly different from that in sham-adrenalectomized animals. In adrenalectomized rats with lower or higher corticosterone levels, bursting pressure was significantly reduced. Thus a narrow range of plasma corticosterone is required for optimal wound healing in this model; higher values tend to impair healing, as do subnormal values, perhaps because of slower protein turnover; low values also lead to high mortality. PMID- 1636783 TI - Salt taste discrimination after bilateral section of the chorda tympani or glossopharyngeal nerves. AB - Gustatory deafferentation of the anterior tongue by bilateral section of the chorda tympani nerve, which removes only 15% of the total taste buds in the rat, severely impaired the rat's ability to discriminate NaCl from KCl. The discrimination deficit was selective. Denervated rats were able to discriminate sucrose from quinine. Despite eliminating four times as many taste buds by bilateral section of the glossopharyngeal nerve, posterior lingual deafferentation had no effect on NaCl vs. KCl discrimination performance. Collectively, these data suggest that afferents in the chorda tympani nerve provide the highest degree of disparity between the peripheral signals representing NaCl and KCl. Electrophysiological findings of others implicate the sodium-specific afferents that appear to exclusively exist in the chorda tympani nerve as the critical elements subserving the NaCl vs. KCl discrimination. PMID- 1636784 TI - Temperature dependence of electrophysiological properties of guinea pig and ground squirrel myocytes. AB - The effects of changing temperature on the electrophysiology of isolated cardiac myocytes of the guinea pig and Richardson's ground squirrel were studied by patch clamp techniques. In cells from both species, the resting membrane potential declined on cooling from 36 to 12 degrees C by approximately 6 mV. The duration of the plateau of the action potential in guinea pig cells increased monotonically on cooling. In contrast, the action potential of ground squirrel cells showed a biphasic response, increasing in duration from 36 to 24 degrees C and then decreasing on cooling from 24 to 12 degrees C. From voltage-clamp studies, the properties of L-type calcium currents (ICa) on cooling were compared in the two species and were found to be similar: In both cases, ICa decreased in amplitude from approximately 2 nA peak current at 36 degrees C to less than 400 pA at 12 degrees C. The Q10 of both the maximum amplitude and time to peak for ICa in both species was approximately 1.8. The time for half inactivation had a greater Q10 of 2.5-3. It is concluded that, surprisingly, factors affecting the resting membrane potential and properties of L-type calcium channels are not major contributors to cardiac dysfunction on cooling. Rather, it is sarcoplasmic reticulum calcium release and reuptake that are likely to be the most important cold-sensitive processes. PMID- 1636785 TI - Cryomicroscopic analysis of freezing in liver of the freeze-tolerant wood frog. AB - The technique of directional solidification coupled with low-temperature scanning electron microscopy was applied to analyze the freezing of liver slices from the freeze-tolerant frog Rana sylvatica. Micrographs of liver slices from 5 degrees C acclimated frogs frozen on the directional stage to -7 degrees C showed continuous ice formed along an expanded vasculature with hepatocytes that were shrunken and virtually dehydrated. However, when frogs were given a survivable freezing exposure at -4 degrees C for 24 h, liver slices subsequently frozen in vitro at -7 degrees C were much less shrunken and the presence of intracellular ice crystals (formed when samples were plunged into liquid N2 before microscopy) demonstrated that ample free water remained in these hepatocytes at -7 degrees C. This reduced level of cell dehydration was correlated with the buildup of 280 +/- 61 mumol/g wet wt glucose as a cryoprotectant in liver during the -4 degrees C exposure in vivo. The study provides the first direct cytological analysis of the freezing process in an organ of a freeze-tolerant vertebrate and the first confirmation of the relationship between maintenance of a critical minimum cell volume and freezing survival by these animals. PMID- 1636786 TI - Sepsis produces early depression of gut absorptive capacity: restoration with diltiazem treatment. AB - Although gut permeability increases and bacterial translocation occurs under certain pathological conditions, it remains unknown whether gut absorptive capacity (GAC) is altered early after the onset of sepsis. The aim of the present study was to investigate this and also to determine whether diltiazem has any effect on GAC in early sepsis. Rats were lightly anesthetized and cecal ligation and puncture (CLP) was performed. A nasogastric tube was inserted, cannulation of various blood vessels was carried out, and the animals were allowed to recover from anesthesia. One hour after CLP, one group of animals received a 1-ml bolus of normal saline intravenously, and another group received diltiazem, 400 micrograms/kg body wt. Sham animals had no CLP performed. GAC was determined by the D-xylose absorption test at 2 and 4 h after CLP. One hour after the administration of D-xylose via the nasogastric tube, its concentration in portal blood was determined colorimetrically. Results show that GAC is significantly depressed at 2 and 4 h after CLP despite the maintenance of normal blood pressure, central venous pressure, and portal pressure. Administration of diltiazem restored GAC to normal levels at 4 h after CLP. Thus diltiazem is a useful adjuvant in the treatment of sepsis because it restores gut absorptive capacity to normal and allows for early enteral nutrition. PMID- 1636787 TI - Strong conservation of the expression of cystatin C gene in choroid plexus. AB - The expression of the cystatin C gene was studied by Northern analysis of RNA isolated from the choroid plexus, other brain tissues, and liver from 11 mammalian and 4 avian species. The probe used for hybridization was cystatin C cDNA isolated previously from a rat choroid plexus cDNA library. Strong conservation of the expression of the cystatin C gene in choroid plexus was suggested by the observation of substantial levels of cystatin C mRNA in choroid plexus RNA from all mammalian and avian species studied. In contrast, levels of cystatin C mRNA in total liver RNA varied widely for mammalian as well as for avian species. It was concluded that the synthesis of cystatin C in choroid plexus has probably been conserved since the stage of the stem reptiles, the common ancestors of mammals and birds. The cystatin C gene was also found to be expressed early in ontogeny, as indicated by the observation of similar cystatin C mRNA levels in choroid plexus RNA from newly hatched and adult chickens. PMID- 1636788 TI - Composition and mechanics of mesenteric resistance arteries from pregnant rats. AB - We tested the hypothesis that the systemic resistance vasculature of the rat is remodeled during pregnancy as evidenced by significant alterations in the passive mechanical properties and extracellular matrix proteins in mesenteric arteries. Mechanical characteristics were determined for arteries from 20-day pregnant rats (n = 6) and age-matched controls (n = 5). Lumen diameter and wall thickness were measured in pressurized arteries (250-microns diameter) using a dimension analyzing system. Distensibility (the relative change in diameter per unit change in pressure) was less in the arteries from the pregnant rats (P less than 0.01). The calculated stress-strain relationships and elastic moduli indicated that the arteries were less stiff by late gestation (P less than 0.05). Ultramicro amino acid analysis and radioimmunoassay were used to measure hydroxyproline, desmosine, and leucine as indicators of collagen, elastin, and total protein, respectively, in similar-sized arteries. Hydroxyproline/leucine (index of collagen) and desmosine/leucine (elastin concentration) decreased 19 and 15% by late gestation (P less than 0.05). The significant alterations in passive mechanics and in extracellular protein content support the concept that arterial wall remodeling in the peripheral vasculature may be one component of the cardiovascular adaptations during pregnancy. PMID- 1636789 TI - Effects of hydration state on exercise thermoregulation in goats. AB - In this study we asked how exercise affects sweating and panting and how dehydration affects exercise thermoregulation in goats. Six goats exercised (4.8 km/h, +10% slope) for 45 min at an ambient temperature of 35 degrees C when hydrated and after 48 h without drinking water. Hematocrit (Hct), plasma protein concentration (PP), and plasma osmolality were elevated by dehydration (P less than or equal to 0.05). Hct and plasma osmolality increased further during exercise in hydrated and dehydrated animals (P less than or equal to 0.05), but PP rose only in hydrated goats (P less than or equal to 0.05). The increase in central blood temperature (Tbl) during exercise was greater in dehydrated than in hydrated animals (P less than or equal to 0.001). Evaporation by panting (Eresp) and sweating were linearly related to Tbl during exercise. The relationship between Eresp and Tbl was not affected by dehydration, but dehydrated animals showed an increased Tbl threshold for sweating. We postulate that the elevation in threshold for sweating may be due primarily to increased body fluid osmolality, and that hypovolemia may not play a significant role in the thermoregulatory adjustments to exercise in dehydrated goats. PMID- 1636790 TI - Comparing responses when each response is a curve. AB - We describe, generalize, and demonstrate the application of a method (W. H. Lawton, A. Sylvestre, and M. S. Maggio, Technometrics 14: 513-532, 1972) that can be used to partially analyze population data. The data from each subject consist of a series of responses observed at distinct values of a predictor variable. The method assumes that all subjects' data originate from a common process but differ because the "units" of predictor and response variables differ among subjects. For example, if the predictor variable is time, time can be "faster" or "slower" from subject to subject. We deal with two different problems. In the first one the response at x for the ith subject is of the form beta 1i + beta 2iG[(x - beta 3i)/beta 4i] + epsilon, where G(x) is a mathematical "shape" function (of the predictor variable x) representing the process and epsilon is observation error. The units of observed and predictor variable are then defined by the values of beta 1i, beta 2i and beta 3i, beta 4i, respectively. In particular beta 1i and beta 3i express shifts and beta 2i, beta 4i express scales of the observed and predictor variables, respectively. In the second problem the response at x for the ith subject is of the form beta 1i + beta 2i integral of x0 G[(s - beta 3i)/beta 4i].Hi(x - s) ds + epsilon, where Hi(x) is a known function. In both problems, the method estimates the common "shape" function G(x) nonparametrically and the parameters beta 1i, beta 2i, beta 3i, and beta 4i for each subject.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636791 TI - Reproducibility of human vagal carotid baroreceptor-cardiac reflex responses. AB - Published information on the reproducibility of human baroreflex responses in the absence of interventions is limited. Therefore, we analyzed retrospectively vagally mediated carotid baroreceptor-cardiac reflex responses of 34 healthy young adult volunteers whom we studied twice, 7-10 days apart (all 34 subjects) or 10 wk apart (8 subjects). We delivered a sequence of neck pressure changes during held expiration: A computer-driven bellows initially raised pressure to approximately 40 mmHg for five heart beats, and then reduced pressure in a stepwise series of R-wave-triggered 15-mmHg decrements to about -65 mmHg. R-R interval changes were plotted as functions of the carotid distending (systolic less neck) pressure occurring within each interval. Each experimental session yielded one stimulus-response relation, which comprised the average of seven separate trials. Six measures were derived from these relations: minimum, maximum, and range of R-R intervals; maximum slope; and operational point [(R-R interval shortening/R-R interval range) x 100%]. Linear regression correlation coefficients for measurements made on two occasions were all highly significant (range: 0.64-0.99). Our results indicate that human vagally mediated carotid baroreceptor-cardiac reflex responses, studied serially under exacting experimental conditions, are highly reproducible. PMID- 1636792 TI - Midbrain central gray: influence on medullary sympathoexcitatory neurons and the baroreflex in rats. AB - The influence of the central gray (CG) of the midbrain on the activity of 19 barosensitive sympathoexcitatory neurons of the rostral ventrolateral medulla (RVLM) and on the sympathetic vasomotor baroreflex was studied in halothane anesthetized rats. Eighteen RVLM barosensitive units were readily activated by train stimulation of the CG, although twin-pulse stimulation was less effective (10 of 19 neurons responded). Inhibition of neurons within the RVLM by bilateral microinjection of the GABA-mimetic drug muscimol abolished the pressor responses to CG stimulation, while the accompanying lumbar nerve sympathoexcitation was converted to sympathoinhibition. In baroreceptor-denervated vagotomized animals, unilateral microinjection of muscimol into the RVLM ipsilateral or contralateral to the site of CG stimulation resulted in approximately equal attenuation of the CG sympathoexcitatory and pressor responses. In contrast, the sympathoexcitatory response to electrical stimulation of the sciatic nerve was reduced more effectively by inhibition of the RVLM contralateral to the site of stimulation. Electrical stimulation of the CG lateral and ventrolateral to the aqueduct produced sympathoexcitation [increased discharge of the greater splanchnic and lumbar sympathetic nerves (SSN and LSN)] with an increase in mean arterial blood pressure. Activation of the SSN by CG stimulation was greater than that observed for the LSN (n = 5 rats). This differential influence of the CG on the sympathetic outflow was not a result of a differential influence of the baroreflex. Electrical stimulation of the CG produced elevations of the gain and the cut-off pressure of the baroreflex for both the SSN and LSN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636793 TI - Endothelium-derived relaxing factor in pulmonary and renal circulations during hypoxia. AB - The pulmonary and renal vasculatures, in contrast to the systemic vasculature, constrict during hypoxia. The endothelium has been implicated in mediating these vascular responses to acute hypoxia via the production of endothelium-derived vasoactive factors. The present study, performed in anesthetized dogs, was designed to investigate the role of endothelium-derived relaxing factor (EDRF) to attenuate the vasoconstrictor response of the pulmonary and renal circulations during acute hypoxia. In response to hypoxia, pulmonary (2.2 +/- 0.3 to 4.5 +/- 0.6 mmHg.l-1.min) and renal (0.60 +/- 0.07 to 0.90 +/- 0.14 mmHg.ml-1.min) vascular resistances increased. Inhibition of endogenous EDRF with NG-monomethyl L-arginine resulted in similar increases in pulmonary (3.0 +/- 0.1 to 4.8 +/- 0.4 mmHg.l-1.min) and renal (0.67 +/- 0.07 to 0.90 +/- 0.09 mmHg.ml-1.min) vascular resistances as in hypoxia. However, in the presence of both hypoxia and EDRF inhibition, an exaggerated pulmonary vascular response was observed (2.2 +/- 0.2 to 7.4 +/- 0.9 mmHg.l-1.min), in contrast to the renal vascular response to EDRF inhibition during hypoxia (0.61 +/- 0.05 to 0.95 +/- 0.10 mmHg.ml-1.min), which was not different from hypoxia or EDRF inhibition individually. The endothelium derived contracting factor endothelin, which modestly increased during hypoxia (11.7 +/- 1.9 to 15.6 +/- 2.4 pg/ml), may also contribute to this vasoconstrictive response to hypoxia. This study suggests in the intact animal that EDRF serves to oppose the pulmonary vasoconstrictor response to hypoxia and further characterizes the role of endothelium-derived factors in the regulation of vascular function during hypoxia. PMID- 1636794 TI - Isoperiodic neuronal activity in suprachiasmatic nucleus of the rat. AB - A subpopulation of neurons in the suprachiasmatic nucleus (SCN) is shown here to exhibit isoperiodic bursting activity. The period of discharge in these cells may be lengthened or the periodicity may be transiently disrupted by photic stimulation. It is suggested that many, if not all, of these cells are vasoactive intestinal polypeptide (VIP) neurons. It is shown that the ultradian periodicity of these cells, estimates of the VIP neuron population size in the SCN, effects of partial lesions on tau (period), and estimates of the phase stability of SCN driven circadian rhythms are consistent with a strongly coupled, multioscillator model of circadian rhythmicity, in which the oscillator population constitutes a restricted subset of the SCN neuronal population. PMID- 1636795 TI - Differences in brown adipose tissue thermogenic responses between Long-Evans and Sprague-Dawley rats. AB - Temperature experiments of 4- and 21 degrees C-acclimated conscious and anesthetized Sprague-Dawley (SD) and Long-Evans (LE) rats revealed that the LE groups or SD rats acclimated to 4 degrees C had significant increases in intracapsular brown adipose tissue (IBAT) temperature above core after ventromedial hypothalamic nucleus (VMH) electrical stimulation or after norepinephrine (NE) infusion (50 micrograms/kg total dose), whereas IBAT temperatures of SD rats (acclimated to 21 degrees C) rose only after intravenous NE. Another study of 21- or 4 degrees C-acclimated SD rats revealed that only the 4 degrees C-acclimated group showed graded increases in IBAT temperature after VMH electrical stimulation as current amplitude or total current duration (not pulse frequency) of the electrical stimulus was increased. In vitro analysis of isolated IBAT tissues of age-matched anesthetized LE or SD rats acclimated to 21 degrees C showed that many indicators of thermogenic capacity including mitochondrial uncoupling protein were significantly lower in the SD group. The results demonstrate that lean male SD rats acclimated to 21 degrees C have suppressed IBAT temperature responses to VMH electrical stimulation compared with lean LE rats due to a reduced thermogenic capacity of that tissue. PMID- 1636796 TI - Diverse effects of calcium channel blockers on skeletal muscle glucose transport. AB - Verapamil, a calcium channel blocker, inhibited the insulin-stimulated glucose transport rate in isolated rat epitrochlearis muscle in a dose-dependent manner (1-200 microM) without affecting basal glucose transport rate. Verapamil's inhibition was rapid in onset and disappearance; changes in glucose transport rate were detectable when verapamil was added to or removed from the incubation medium 15 min prior to measurement of glucose transport. Verapamil also inhibited the stimulation of muscle glucose transport caused by hypoxia, indicating that the effect was not limited to insulin action. Although the optical isomers of verapamil vary considerably in their potency as Ca2+ channel blockers, they were equally effective inhibitors of insulin-stimulated glucose transport rate. Nifedipine (10-200 microM), a more potent blocker of skeletal muscle Ca2+ channels than verapamil, was less effective as an inhibitor of insulin-stimulated glucose transport. Furthermore, nifedipine (10 microM) did not inhibit hypoxia stimulated glucose transport. Diltiazem (200 microM), another Ca2+ channel blocker, did not reduce insulin-stimulated glucose transport. PMID- 1636797 TI - Differential baroreceptor reflex modulation by centrally infused angiotensin peptides. AB - The present study was designed to investigate the effect of intracerebroventricular (icv) and intravenous (iv) infusion of angiotensin (ANG) (1-7), ANG III, and ANG II on the baroreceptor control of heart rate (BHR) in conscious rats. Reflex changes in HR were elicited by bolus iv injection of either phenylephrine or sodium nitroprusside before and within 1 and 3 h of icv infusion of ANG II (n = 10), ANG III (n = 9), ANG-(1-7) (n = 9), or saline (n = 9) at a rate of 3 nmol.7.5 microliter-1.h-1. In another group of animals (n = 23), iv infusion of the same amount of ANG peptides was carried out at a rate of 0.7 ml/h. The average ratio of changes in HR in beats per minute and changes in mean arterial pressure (MAP, mmHg) was used as an index of BHR sensitivity. ANG II and ANG III produced a significant increase in the basal levels of MAP, but only during the first hour of infusion (iv or icv). No significant changes in baseline HR were observed. ANG-(1-7) and saline infusion did not change basal levels of HR or MAP (iv or icv). ANG II (iv and icv) and ANG III (icv) caused a significant decrease in the BHR sensitivity for reflex bradycardia. In contrast, icv infusion of ANG-(1-7) induced a significant increase in BHR sensitivity for reflex bradycardia (-3.0 +/- 0.3, 1 h, and -2.8 +/- 0.1 beats.min-1.mmHg-1, 3 h vs. -2.1 +/- 0.2 beats.min-1.mmHg-1, before infusion).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636798 TI - Hypertonic NaCl inhibits gastric motility and food intake in rats with lesions in the rostral AV3V region. AB - Several diverse treatments that stimulate pituitary secretion of oxytocin (OT) in rats produce a parallel inhibition of gastric motility and food intake. The present experiments demonstrate that injection of hypertonic saline (HS) is another such treatment. Systemic administration of large doses of OT had no effect on gastric motility. Lesions within the region anteroventral to the third ventricle (AV3V region) severely impaired the drinking response to HS without affecting its inhibition of either gastric motility or food intake. These and other results suggest that despite the close association of pituitary secretion of OT with inhibition of both gastric motility and food intake in intact animals after HS administration, these effects may be dissociated by lesions within the AV3V region. Consequently, osmosensitive cells located within the periventricular tissue of the rostral AV3V region, which are critical for the stimulation of thirst and pituitary OT secretion after systemic injection of HS, do not appear to be essential for the parallel inhibition of gastric motility and food intake produced by this treatment in rats. PMID- 1636799 TI - Circulatory dynamics during periodic intracranial hypertension in fetal sheep. AB - The human fetal head is periodically compressed during labor. The resulting increase in intracranial pressure (ICP) may exceed the hydrostatic increase in mean arterial pressure (MAP), thereby decreasing cerebral perfusion pressure (CPP). We determined whether the cardiovascular system of near-term fetal sheep is capable of rapidly increasing MAP during periodic increases in ICP. In 12 chronically instrumented fetuses, we produced sinusoidal oscillations in ICP with a maximum of 52 +/- 1 mmHg (baseline MAP) and a minimum of 4 +/- 1 mmHg at a 3 min periodicity by ventricular fluid infusion and withdrawal. Phasic increases in MAP and decreases in electromagnetically determined renal blood flow tracked behind ICP by 0.3-0.5 min. By the sixth cycle, tonic peripheral vasoconstriction that occurred attenuated by the reduction in CPP during subsequent ICP oscillations. By the 10th cycle, plasma catecholamines and vasopressin increased 20-fold. To more closely simulate the pattern during labor, we produced an ICP triangular pulse train with 5-min periodicity and pulse duration of 1.5 min in six other fetuses. The MAP response was nearly out of phase with this more rapid rise of ICP. Thus the phasic component of the fetal pressor response is inadequate for maintaining CPP when ICP is increased to baseline MAP in less than 0.75 min. However, when the ICP pulse duration and frequency are sufficiently high, a tonic pressor response that may be humorally mediated acts to minimize transient cerebral ischemia. PMID- 1636800 TI - The psychotherapist as witness for the prosecution: the criminalization of Tarasoff. AB - The "duty to protect" doctrine heralded by the Tarasoff decision seeks to prevent physical harm to third parties by psychiatric patients. Recent court cases have mandated the testimony of a criminal defendant's psychotherapist both about the Tarasoff warning itself and about confidential treatment information that was associated with the warning. One court further ruled that some clinical sessions were not psychotherapy and therefore were not afforded the protection of psychotherapist-patient privilege. The continuing erosion of confidentiality has resulted in psychiatrists and other mental health professionals becoming prosecution witnesses at the criminal trials of their own patients. PMID- 1636801 TI - Decreased brain metabolism in neurologically intact healthy alcoholics. AB - OBJECTIVE: The extent to which cerebral dysfunction in alcoholics is related to the direct effects of alcohol in the brain rather than to indirect mechanisms and/or alcohol withdrawal remains unclear. The purpose of this study was to evaluate whether healthy alcoholics with no evidence of alcohol-associated complications showed changes in brain glucose metabolism. METHOD: Positron emission tomography and [18F]-fluorodeoxyglucose were used to measure regional brain metabolism. The study group consisted of 22 normal, healthy, right-handed volunteers and 22 neurologically intact, healthy, right-handed alcoholics tested 6 to 32 days after alcohol discontinuation. RESULTS: Alcoholics showed significantly lower whole brain metabolism than normal control subjects. Normalization of regional metabolic values to the whole brain metabolic rate revealed that the left parietal and right frontal cortices were the most affected regions. Although the whole brain metabolic rate was correlated with the amount of time since alcohol discontinuation, the "normalized" decreases in left parietal and right frontal glucose metabolism were not. CONCLUSIONS: These findings support the contribution of the direct effect of alcohol as well as alcohol withdrawal on the changes in regional brain metabolism seen in alcoholics. They also provide evidence of cerebral changes in neurologically intact healthy alcoholics. PMID- 1636802 TI - Hypothalamic-pituitary-adrenal axis hyperactivity and psychosis: recovery during an 8-year follow-up. AB - OBJECTIVE: An earlier study showed that the results of dexamethasone suppression test (DST) predicted outcome among patients with a functional psychosis followed to 1 year. The present study was undertaken to replicate these findings with a different patient group and a longer follow-up. METHOD: Ninety-two inpatients with nonorganic, nonmanic psychoses had DSTs during their hospitalizations. Raters who were blind to DST results, and to baseline chart or research diagnoses, conducted personal interviews with 71 of the patients 8 years later. RESULTS: Patients who had been nonsuppressors on the DST were five times more likely than those who had been suppressors to be free of psychotic features and to exhibit insight at the follow-up interview (42% versus 8%). Prognostic differences between these groups were clear within the first year of follow-up. Baseline diagnoses also strongly predicted outcome, even among DST nonsuppressors, and DST results had no prognostic significance among patients with a baseline diagnosis of schizophrenia. Later ages at onset and short episode durations at intake also predicted recovery, but baseline DST suppressor status remained important after control for these factors. CONCLUSIONS: The findings of this study and those of the earlier follow-up suggest that among patients with a functional psychosis, nonsuppression on the DST is prognostically important, particularly after the exclusion of those who meet narrow criteria for schizophrenia. PMID- 1636803 TI - The dexamethasone suppression test in adolescent outpatients with major depressive disorder. AB - OBJECTIVE: The purpose of the study was to determine whether the dexamethasone suppression test (DST) would discriminate between outpatient adolescents with major depressive disorder and normal adolescent comparison subjects. METHOD: Depressed patients were accepted into the study only if they fulfilled the Research Diagnostic Criteria for major depressive disorder. The depressed subjects (N = 44) and the normal subjects (N = 38) were studied in the same environment and under the same conditions. The subjects received 1 mg of dexamethasone at 11:00 p.m. The next day, blood for determining plasma cortisol concentrations was drawn through an indwelling catheter every 60 minutes from 8:00 a.m. until 11 p.m. RESULTS: After dexamethasone, the cortisol levels of the adolescents with major depressive disorder and the normal subjects were not significantly different. Only six (14%) of the depressed subjects and one (3%) of the normal subjects showed evidence of nonsuppression (cortisol value greater than 5 micrograms/dl). Analyses of subgroups of the depressed patients based on suicidal tendencies and endogenous subtype also failed to reveal significant differences in cortisol values. Estimates of the severity of depression showed significant negative correlations with cortisol values among the depressed patients. CONCLUSIONS: In contrast with previous studies of adolescent inpatients, the DST did not discriminate between the adolescent outpatients with major depressive disorder and the normal comparison subjects in this study. Possible reasons for the discrepancies, such as severity of the depression and inpatient status, are discussed. PMID- 1636804 TI - Relapse after cognitive behavior therapy of depression: potential implications for longer courses of treatment. AB - OBJECTIVE: The authors studied the risk of relapse among depressed patients after cognitive behavior therapy in order to document the need and potential indications for longer-term models of treatment. METHOD: Forty-eight patients with major depression who responded during a 16-week course of cognitive behavior therapy entered a 1-year prospective follow-up study, as did two patients who received 20 weeks of therapy. Standardized, independent clinical assessments were completed 1, 3, 6, 9, and 12 months after treatment. Relapse was defined as, at minimum, a 2-week period in which the subject met the DSM-III-R criteria for major depression and had a Hamilton depression scale score of 15 or more. RESULTS: Sixteen patients (32%) relapsed during the 1-year follow-up. Correlates of relapse included a history of depressive episodes, higher levels of depressive symptoms and dysfunctional attitudes, slower response to therapy, and being unmarried. Patients who fully recovered during therapy (Hamilton depression score of 6 or less for 8 weeks or more) were at significantly lower risk for relapse than those who partially recovered (9% and 52%, respectively). Slower response to therapy, unmarried status, and high residual scores on the Dysfunctional Attitudes Scale were independently and additively related to increased risk of relapse. CONCLUSIONS: These findings provide further evidence of a relation between residual symptoms and relapse after cessation of active treatment. The authors strongly recommend that models of longer-term psychotherapy be developed for depressed patients who do not recover fully during time-limited cognitive behavior therapy. PMID- 1636805 TI - Protective effects of imipramine maintenance treatment in panic disorder with agoraphobia. AB - OBJECTIVE: This study was designed to assess and compare the differential relapse rates of patients with panic disorder and agoraphobia after discontinuation of acute treatment (6 months) or acute plus maintenance treatment (18 months) with imipramine. METHOD: Sixteen patients with panic disorder and agoraphobia who had shown marked and stable response to 6 months of acute imipramine treatment and a comparable group of 14 patients who had been in remission during an additional year of half-dose imipramine maintenance treatment entered a 3-month, double blind discontinuation study followed by a 3-month drug-free period. Assessments of the patients were made according to operationalized response/relapse criteria, and plasma drug concentrations were monitored. RESULTS: Survival analysis revealed significantly different cumulative probabilities of continued response 6 months after discontinuation of imipramine treatment between the patients who had received only acute treatment and those who had received acute and maintenance treatment. CONCLUSIONS: The results support the hypothesis that successful imipramine maintenance treatment of patients with panic and agoraphobia can have protective effects against relapse, at least in the first 6 months after the maintenance treatment period. PMID- 1636806 TI - The latent structure of anxiety symptoms in anxiety disorders. AB - OBJECTIVE: Research in the psychopathology of panic and anxiety disorders, particularly agoraphobia, suggests that fear of fear may be the basis of these conditions. However, there is little empirical research on the definition and validity of the concept of fear of fear in a clinical study group. The authors' aims are 1) to determine empirically if particular associations between symptoms and beliefs exist in a group of patients with anxiety disorders and what underlying dimensions of perceived threat they represent and 2) to assess the relative importance of these associations in agoraphobia with panic attacks, panic disorder, social phobia, and generalized anxiety disorder. METHOD: In an anxiety disorders treatment unit, 390 outpatients with anxiety disorders diagnosed according to DSM-III criteria completed the Anxiety Symptoms and Beliefs Scale. RESULTS: A principal components analysis of the patients' ratings on the Anxiety Symptoms and Beliefs Scale produced a four-factor solution in which specific sets of anxiety symptoms loaded with specific beliefs. These four factors were interpreted as respiratory symptoms, vestibular symptoms, autonomic arousal, and psychological threat. Respiratory and vestibular symptoms were more associated with panic disorder diagnoses than with social phobia and generalized anxiety disorder diagnoses. CONCLUSIONS: These findings support a conception of fear of fear in anxiety disorders as fearful beliefs concerning the experience of anxiety symptoms. Associations between symptoms and fear of fear are present across anxiety disorders but are most pronounced in agoraphobia with panic attacks. PMID- 1636807 TI - Are males more likely than females to develop schizophrenia? AB - OBJECTIVE: This study was undertaken to determine whether the incidence of schizophrenia is equivalent for males and females. METHOD: An attempt was made to identify every first-episode case of psychosis in a large Canadian city over a period of 2 1/2 years. A comprehensive referral network was established that included hospital and community settings where psychotic persons might appear. More than 300 potential subjects were identified, 175 of whom underwent a structured psychiatric interview and were assigned diagnoses according to five different diagnostic systems. RESULTS: The incidence of schizophrenia was two to three times higher among males than among females. Even though the use of different diagnostic systems yielded slightly different risk rates, the elevated risk for males remained consistent. There were no differences between the sexes in the incidence of affective psychosis. In comparison with schizophrenia, the incidence rates for mood disorders with psychotic features were sometimes lower and sometimes higher, depending on the diagnostic system used. CONCLUSIONS: The findings, coupled with reports in the past 10 years from other investigators, challenge the conventional belief that the incidence of schizophrenia is the same for the two sexes. PMID- 1636808 TI - A monozygotic mirror-image twin pair with discordant psychiatric illnesses: a neuropsychiatric and neurodevelopmental evaluation. AB - One piece of genetic evidence for the biological distinctness of schizophrenia and bipolar illness is the rarity of monozygotic twin pairs in which one twin suffers from schizophrenia and the other from bipolar disorder. The authors describe a pair of monozygotic mirror-image twins with discordant diagnoses, schizophrenia in one twin and bipolar or schizoaffective disorder in the other. PMID- 1636809 TI - Interictal psychiatric morbidity and focus of epilepsy in treatment-refractory patients admitted to an epilepsy unit. AB - Of 71 consecutive patients admitted to an epilepsy unit of a general hospital, 32 (45%) were classified as having psychiatric disorders by using the General Health Questionnaire. No differences were evident to support a specific relationship between the type or focus of epilepsy and psychopathology. PMID- 1636810 TI - Neurobehavioral functioning in a nonconfounded group of asymptomatic HIV seropositive homosexual men. AB - Neurobehavioral functioning was tested in 34 asymptomatic HIV-seropositive and 43 HIV-seronegative male homosexual subjects without substance abuse and CNS disorders. The HIV-positive subjects exhibited mild motor slowing compared to the seronegative subjects. These differences remained after controlling for potential cofactors. Early neurobehavioral impairment in HIV infection seems limited to subclinical motor deficits and attributable to HIV rather than possible confounding factors. PMID- 1636811 TI - Sudden self-harm while taking fluoxetine. PMID- 1636812 TI - Fluoxetine-induced anorexia in a bulimic patient. PMID- 1636813 TI - Lyell syndrome and lethal catatonia: a case for ECT. PMID- 1636814 TI - Schizophrenia and chromosomal fragile sites. PMID- 1636815 TI - Serotonin syndrome. PMID- 1636816 TI - The (Ab)use of computers. PMID- 1636817 TI - Alcohol and addictions. PMID- 1636818 TI - Alcohol and addictions. PMID- 1636819 TI - Kleptomania and shoplifting. PMID- 1636820 TI - Clozapine concentrations and clinical response in schizophrenic patients. PMID- 1636821 TI - Identification of mood variance in depression. PMID- 1636822 TI - Twins and eating disorders. PMID- 1636823 TI - Regarding the use and accuracy of the family history method. PMID- 1636824 TI - Credibility of patients in psychiatric research. PMID- 1636825 TI - Recovery and shorter duration of hospitalization. PMID- 1636826 TI - Socioeconomic differences in mortality in Britain and the United States. PMID- 1636827 TI - National mortality rates: the impact of inequality? AB - Although health is closely associated with income differences within each country there is, at best, only a weak link between national mortality rates and average income among the developed countries. On the other hand, there is evidence of a strong relationship between national mortality rates and the scale of income differences within each society. These three elements are coherent if health is affected less by changes in absolute material standards across affluent populations than it is by relative income or the scale of income differences and the resulting sense of disadvantage within each society. Rather than socioeconomic mortality differentials representing a distribution around given national average mortality rates, it is likely that the degree of income inequality indicates the burden of relative deprivation on national mortality rates. PMID- 1636828 TI - The Roseto effect: a 50-year comparison of mortality rates. AB - OBJECTIVES: Earlier studies found striking differences in mortality from myocardial infarction between Roseto, a homogeneous Italian-American community in Pennsylvania, and other nearby towns between 1955 and 1965. These differences disappeared as Roseto became more "Americanized" in the 1960s. The present study extended the comparison over a longer period of time to test the hypothesis that the findings from this period were not due to random fluctuations in small communities. METHODS: We examined death certificates for Roseto and Bangor from 1935 to 1985. Age-standardized death rates and mortality ratios were computed for each decade. RESULTS: Rosetans had a lower mortality rate from myocardial infarction over the course of the first 30 years, but it rose to the level of Bangor's following a period of erosion of traditionally cohesive family and community relationships. This mortality-rate increase involved mainly younger Rosetan men and elderly women. CONCLUSIONS: The data confirmed the existence of consistent mortality differences between Roseto and Bangor during a time when there were many indicators of greater social solidarity and homogeneity in Roseto. PMID- 1636830 TI - Car size or car mass: which has greater influence on fatality risk? AB - OBJECTIVES: Proposed increases in corporate average fuel economy standards would probably lead to lighter cars. Well-established relationships between occupant risk and car mass predict consequent additional casualties. However, if size, not mass, is the causative factor in these relationships, then decreasing car mass need not increase risk. This study examines whether mass or size is the causative factor. METHODS: Data from the Fatal Accident Reporting System are used to explore relationships between car mass, car size (as represented by wheelbase), and driver fatality risk in two-car crashes. RESULTS: When cars of identical (or similar) wheelbase but different mass crash into each other, driver fatality risk depends strongly on mass; the relationship is quantitatively similar to that found in studies that ignore wheelbase. On the other hand, when cars of similar mass but different wheelbase crash into each other, the data reveal no dependence of driver fatality risk on wheelbase. CONCLUSIONS: Mass is the dominant causative factor in relationships between driver risk and car size in two-car crashes, with size, as such, playing at most a secondary role. Reducing car mass increases occupant risk. PMID- 1636829 TI - HMO membership, treatment, and mortality risk among prostatic cancer patients. AB - OBJECTIVES: Treatment and mortality risk were compared between prostate cancer patients receiving care in fee-for-service settings and those receiving care in a health maintenance organization (HMO). METHODS: Two samples were obtained from a population-based tumor registry. Patients in the first sample (n = 201) were interviewed shortly after diagnosis to obtain data on income, education, overall health status, and expenditures for health status, and expenditures for health care. These data were combined with information from the tumor registry on cancer stage, age, treatment, place of residence, and source of care. Only tumor registry data were obtained for most patients in the second sample (n = 962). For both samples, survival time was monitored for up to 80 months. RESULTS: Multivariate analysis of data from the interviewed sample indicated that HMO patients were less likely to receive surgery but more likely to receive radiation therapy than were those in fee-for-service settings. Mortality risk was lower for the HMO patients than for those in fee-for-service plans. Findings based on the second sample were nearly identical. CONCLUSIONS: This study suggests that HMOs may offer important advantages to lower-income patients at risk for specific life threatening diseases. PMID- 1636831 TI - The development of registries for surveillance of adult lead exposure, 1981 to 1992. AB - OBJECTIVES: Since 1981, 15 states have established registries for surveillance of adult lead absorption, primarily based on reports of elevated blood lead levels from clinical laboratories. I review the status of the registries and recommend steps for further development. METHODS: Companies reported to the New York registry are compared with those cited by the Occupational Safety and Health Administration (OSHA). I present data on US workers and plants with potential lead exposures and blood tests, as well as review registries' reporting requirements. RESULTS: Registries identify many companies not cited by the Occupational Safety and Health Administration, but underreporting occurs because (1) reporting is usually not required from laboratories outside the state, (2) most registries use a blood lead reporting level of 1.21 mumol/L, which excludes many exposed workers, and (3) many companies with potential exposures do not have routine monitoring programs. CONCLUSIONS: Registries' reporting requirements and procedures should be standardized, including a blood lead reporting level of 0.72 mumol/L. Elevated blood lead levels should be a reportable condition nationwide, and a comprehensive national surveillance system should be established: clinical laboratories should be required to report cases to those states with lead registries or directly to the national adult lead registry. PMID- 1636832 TI - Lower respiratory illness in infants and low socioeconomic status. AB - OBJECTIVES: Infants from families of low socioeconomic status are said to suffer higher rates of lower respiratory illness, but this assertion has not been carefully examined. METHODS: We studied the frequency and determinants of lower respiratory illness in infants of different socioeconomic status (n = 393) by analyzing data from a community-based cohort study of respiratory illness during the first year of life in central North Carolina. RESULTS: The incidence of lower respiratory illness was 1.41 in the low socioeconomic group, 1.26 in the middle group, and 0.67 in the high group. The prevalence of persistent respiratory symptoms was 39% in infants in the low socioeconomic group, 24% in infants in the middle group, and 14% in infants in the high group. The odds of persistent respiratory symptoms in infants of low and middle socioeconomic status were reduced after controlling for environmental risk factors for lower respiratory illness. Enrollment in day care was associated with an increased risk of persistent symptoms among infants of high but not low socioeconomic status. CONCLUSIONS: Infants of low socioeconomic status are at increased risk of persistent respiratory symptoms. This risk can be partly attributed to environmental exposures, most of which could be changed. PMID- 1636833 TI - Imported leprosy in the United States, 1978 through 1988: an epidemic without secondary transmission. AB - OBJECTIVES: Leprosy remains a major health problem in many regions of the world. In the United States, although leprosy continues to be reported, approximately 90% of cases are imported (i.e., occur among immigrants and refugees). An increase in imported cases began in 1978. This study was conducted to analyze this trend and to characterize the contributing cases. METHODS: Centers for Disease Control leprosy surveillance data from 1971 through 1988 were analyzed. RESULTS: The number of imported cases reported annually was relatively constant from 1971 through 1977 (mean = 119 per year), increased to 307 in 1985, and then decreased to 102 in 1988. Of the 957 excess cases reported from 1978 through 1988, 73.4% were among persons from Southeast Asia, including 51.3% from Vietnam, Cambodia, and Laos (Indochina). There was no coincident increase in indigenous cases of leprosy; the mean annual number of such cases was 17.7 (range = 10 to 29). Leprosy remains endemic in Texas, Hawaii, Louisiana, and possibly California. CONCLUSIONS: An epidemic of imported leprosy began in the United States in 1978, peaked in 1985, and ended by 1988. This increase was primarily due to cases among refugees from Indochina and was limited by a decrease in the influx of Indochinese refugees in the mid-1980s. There is no evidence that these cases resulted in transmission in the United States. PMID- 1636834 TI - Socioeconomic status and childhood mortality in North Carolina. AB - Children in families eligible to receive Aid to Families with Dependent Children (AFDC) were found to have substantially higher mortality rates than non-AFDC children. The disparity seems to be greater for Whites than for non-Whites. These results suggest the presence of social class differentials in access to and use of health care and related services and facilities, in exposure to environmental risks, and in knowledge of injury control measures. PMID- 1636835 TI - Does equal socioeconomic status in black and white men mean equal risk of mortality? AB - Although concerns have been expressed that mortality from coronary disease and all other causes is greater among Blacks than Whites, we hypothesized that, when socioeconomic status is adequately considered, mortality inequalities between Blacks and Whites are insignificant. The study population was a random sampling of Black and White men who were 35 years of age or older when recruited into the Charleston Heart Study in 1960. Education level and occupational status at baseline were used to compare mortality over the ensuing 28 years between Black and White men, who were classified as low or high socioeconomic status. In no instance were Black-White differences in all-cause or coronary disease mortality rates significantly different when socioeconomic status was controlled. We conclude that socioeconomic status is an important predictor of mortality and that, when socioeconomic status is considered, differences in Black-White mortality rates may be small. PMID- 1636836 TI - Job strain and mortality in elderly men: social network, support, and influence as buffers. AB - The aim was to investigate whether job strain affects mortality in a representative population of elderly men, and whether social network and social support outside the workplace can buffer the negative health effects of job strain. A higher relative mortality risk (RR) was found among men exposed to job strain (RR = 1.7). The combination of exposure to job strain and seven different measures of weak social network and social support was associated with a further increased RR ranging from 2.1 to 4.6. PMID- 1636837 TI - Mortality and the attribution of health problems to aging among older adults. AB - This study examined the association between mortality and attributing health problems to aging among 1391 respondents from the Longitudinal Study of Aging who indicated difficulty with activities of daily living. Of this number, 72 persons attributed impairment primarily to "old age." Logistic regression controlling for demographics, physical health problems, self-rated health, and social involvements showed an association with mortality (adjusted odds ratio = 1.78, CI = 1.05, 3.00). Attributing health problems to aging may carry a risk of adverse health events. PMID- 1636838 TI - Use of cardiovascular disease medications and mortality in people with older onset diabetes. AB - Mortality follow-up for a cohort defined in 1980 with diabetes diagnosed at 30 years of age or older has been completed through 1988. History of medication use was obtained during the initial evaluation. There were 605 (44.2%) confirmed deaths; heart disease was the underlying cause in 49.9% of the deaths. Use of loop diuretics was associated with an odds ratio of death of 1.8 (95% CI = 1.4, 2.2). Although a causal relationship cannot be inferred, it is reasonable to suggest that blood chemistries be monitored regularly in persons on these drugs since electrolyte imbalance may be related to death. PMID- 1636839 TI - The accuracy of the National Death Index when personal identifiers other than Social Security number are used. AB - This study analyzed the accuracy of the National Death Index when personal identifiers were used that included or excluded Social Security number. Computerized records of the Department of Veterans Affairs were used for comparison. Different combinations of identifiers other than Social Security number correctly identified from 83 to 92 percent of dead and 92 to 99 percent of living persons. These results should prove useful in ascertaining the mortality status of patient populations without information on Social Security numbers. PMID- 1636840 TI - Race and sex differences in mortality following fracture of the hip. AB - This paper describes the all-cause mortality experience, following a fracture of the hip, of 712,027 persons covered by the Medicare program from 1984 through 1987. White women experienced the lowest mortality rate (17.2 per 1000 person months), followed by Black women (22.9 per 1000 person-months), Black men (33.5 per 1000 person-months), and White men (33.7 per 1000 person-months). The observed race-sex differences in survival were found at all ages and regardless of the number of comorbid conditions listed with the discharge diagnosis. While these data demonstrate marked race-sex differences in survival following hip fracture, the cause of these differences is not immediately apparent and demands further investigation. PMID- 1636841 TI - Seroprevalence of HIV-1 and hepatitis B and C in prostitutes in Albuquerque, New Mexico. AB - A survey of persons soliciting sex in an area known to be frequented by prostitutes in Albuquerque, NM, included 43 females and 66 males. Seroprevalence rates found in this population-based study were as follows: human immunodeficiency virus type 1 (HIV-1), 3%; hepatitis B, 39%; hepatitis C, 45%. Increased age, intravenous drug use, and condom use were independent risk factors for hepatitis B. Female gender and intravenous drug use were independent risk factors for hepatitis C. Neither sharing injection equipment nor engaging in receptive anal intercourse was independently associated with hepatitis B or C. PMID- 1636842 TI - Decreased access to medical care for girls in Punjab, India: the roles of age, religion, and distance. AB - Risk factors that increase the likelihood of discrimination against girls in India have not been well studied. In this study of hospitalized children in Punjab, India, girls were less likely to be in the newborn or infant age groups, to be of the Sikh religion, or to come from far away than were boys. These differences suggest that these factors are significant risk factors for denied access to medical care for girls living in Punjab, India. PMID- 1636843 TI - Biotechnology products in the field: bringing regulation closer to home. PMID- 1636844 TI - Project Together: serving substance-abusing mothers and their children in Des Moines. PMID- 1636845 TI - Mortality among minority populations in the United States. PMID- 1636846 TI - Ethnic differences in nicotine exposure. PMID- 1636847 TI - Estimation of small area population denominators. PMID- 1636848 TI - Suicide by the elderly. PMID- 1636849 TI - Firefighters and heart disease. PMID- 1636850 TI - Dissimilarities between Tuskegee Study and HIV/AIDS programs emphasized. PMID- 1636851 TI - Handedness, traffic crashes, and defensive reflexes. PMID- 1636852 TI - The GORE-TEX anterior cruciate ligament prosthesis. A long-term followup. AB - The GORE-TEX anterior cruciate ligament prosthesis has been implanted in 268 patients at our institution since April of 1984. Follow-up for this study was available on 70% of these patients (188). Eighty-one percent (152) of these had the ligament for chronic injuries, 14% (26) for acute, and 5% (10) for subacute injuries. The patient population had an average age of 27.6 years (SD = 8.4) and a Tegner activity score of 6.05 (SD = 1.53). Prior procedures had been performed on 56% (105) of the patients. Concomitant procedures were performed in 73% (137) and included iliotibial band tenodesis, partial meniscectomy, posterior oblique ligament advancement, or meniscal repair. Followup averaged 48 months (range, 24 to 68). Evaluation included a questionnaire, physical examination, radiographs, KT-1000 arthrometer testing, and an activity score. Results were graded as excellent, good, fair, and poor. Acceptable results (good and excellent) were obtained in 83 patients (44%). Fifty-eight patients (32%) were rated excellent and 25 (13%) were rated good. Unacceptable results (fair and poor) were obtained in 105 patients (56%). Twenty-five patients (13%) were rated fair and 80 (42%) were rated poor. Subjective improvement was indicated by 166 patients (88%). Activity levels postoperatively as rated by the Tegner Scale improved in 2 (1%), remained the same in 167 (89%), and decreased in 19 patients (10%). Effusions occurred in 63 patients (34%) and caused an unacceptable result in 22 (12%). Rupture occurred in 23 patients (12%). Loosening greater than 3 mm occurred in 64 patients (34%) and led to unacceptable results in 37 (20%). Infection occurred in 5 patients (2.7%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636853 TI - Arthroscopic staple capsulorrhaphy for anterior shoulder instability. AB - We reviewed the results of the arthroscopic staple capsulorrhaphy on 47 patients with a followup of 4 years. Thirty-four of the 47 shoulders had a history of traumatic dislocation, while the remaining 13 had a history of subluxation. The recurrence rate was 25%, with 8 shoulders developing recurrent frank dislocation and 4 developing subluxation. Only 21 of the 47 patients were able to resume normal sporting activities after surgical repair. We had no cases of staple loosening within the joint, but we did have 3 patients whose staples were removed because of persistent pain in the shoulder. PMID- 1636854 TI - The effect of external ankle support in chronic lateral ankle joint instability. An electromyographic study. AB - We examined the effect of ankle taping on ankle joint stability by measuring mechanical stability using standardized stress radiographs. Anterior talar translation and talar tilt, both with and without ankle tape, were examined. The reduction of anterior talar translation and talar tilt with tape as compared to without tape was insignificant. The reaction time of the peroneus muscles was measured by electromyographic signal after a simulated ankle sprain on a tilting trapdoor. The reaction time was significantly slower in the unstable ankles of 20 athletes with unilateral ankle instability than in the stable contralateral ankles. With tape, the reaction time was significantly shortened, although not back to normal. The greatest improvement in reaction time was achieved in ankles with the highest degree of mechanical instability. Thus, the mechanism behind the function of ankle tape may be to restrict the extremes of ankle motion and to help shorten the reaction time of the peroneus muscles by affecting the proprioceptive function of the ankle. PMID- 1636855 TI - The effects of anabolic steroids on collagen synthesis in rat skeletal muscle and tendon. A preliminary report. AB - We measured the activities of prolyl 4-hydroxylase and galactosylhydroxylysyl glucosyltransferase (both enzymes of collagen biosynthesis) and the concentration of hydroxyproline in male rat soleus muscle and Achilles tendon during anabolic steroid treatment at 1 and 3 weeks. The rats were treated using a therapeutic dosage or a dosage that was five times the therapeutic level. After 1 week, the activity of prolyl 4-hydroxylase decreased significantly (P less than 0.01) in both treated groups in the soleus muscle, but the activity of galactosylhydroxylsyl glucosyltransferase decreased significantly (P less than 0.05) only in the group given a therapeutic dose. After 3 weeks, the activities were at the control level. In the Achilles tendon, the activity of prolyl 4 hydroxylase and the hydroxyproline concentration decreased significantly (P less than 0.05) in the group given high doses at 3 weeks. Anabolic steroid treatment seems to have at least a transitory effect on collagen biosynthesis in male rat muscle and tendon; in tendon this effect is seen only with high doses. PMID- 1636856 TI - A profile of the musculoskeletal characteristics of elite professional ballet dancers. AB - Twenty-eight principal dancers and soloists from America's two most famous ballet companies were examined for anthropometric measurements, including flexibility, muscle strength, and joint range of motion. Both male and female dancers were flexible, but not hypermobile, and did not differ significantly from each other. Marked differences were found between the range of motion of the hip and ankle in the dancers and the norms for the general population. The increased external rotation of the hip in women was accompanied by a loss in internal rotation, resulting in an increased range of motion with an externally rotated orientation. The men, however, lost more internal rotation than they gained in external rotation. These data raise the possibility of a torsional component to the turned out hip position in elite female professional ballet dancers. In addition, significant anatomic differences separate elite dancers of both sexes from the normal population. PMID- 1636857 TI - Long-term functional results in patients with anterolateral rotatory instability treated by iliotibial band transfer. AB - The purpose of this paper is to define the use of the extraarticular, lateral reconstruction in the spectrum of patients with cruciate deficiency. A review was conducted of 112 consecutive patients with a MacIntosh-type iliotibial band transfer done between 1972 and 1986. Fifty-six of the patients had a partial or complete meniscectomy, and 24% had failed a previous extraarticular procedure. Eighty-one percent were men, with a mean age of 23. Twenty-five percent of the patients had radiographic degenerative changes at the knee at the outset. Ninety eight percent had an anterior drawer of 1+ or greater; 97% had a pivot shift greater than trace. All patients had symptomatic knee instability. Seventy-seven of the 112 patients (69%) were available for followup (range, 24 months to 15.5 years; median, 7.6). Twenty-three patients (21%) returned for examination, KT 1000 and Cybex testing, and radiographs. An additional 54 patients (48%) were seen by their local physicians or returned a detailed questionnaire that included the Cincinnati knee rating scale. At final followup, 38% complained of some knee instability, 36% had recurrent effusions, 61% had intermittent pain, 79% had radiographic gonarthrosis, and 25% had undergone additional surgery. Forty-two percent had a positive Lachman after surgery, and only 15% had a pivot shift. The mean knee score was 81.1. Previous extraarticular anterior cruciate ligament reconstruction, meniscectomy, and generalized ligamentous laxity were associated with a significant decrement in the knee rating (P = 0.05). Ligamentous laxity strongly correlated with symptoms of giving way.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636858 TI - Anterior cruciate ligament-medial collateral ligament injury: nonoperative management of medial collateral ligament tears with anterior cruciate ligament reconstruction. A preliminary report. AB - We present the results of a series of patients who had nonoperative management of the medial collateral ligament with anterior cruciate ligament reconstruction. From February 1983 through December 1989, 84 of 90 consecutive patients were available for followup (minimum, 1 year; mean, 3.1 years) with a combined anterior cruciate ligament-medial collateral ligament injury (anterior cruciate ligament rupture and medial collateral ligament tear) received surgical management by the same physician. The last 68 of these 84 patients who met the inclusion criteria underwent patellar tendon graft for anterior cruciate ligament reconstruction, with concomitant nonoperative management of medial collateral ligament tears. Follow-up evaluation consisted of physical examination for medial laxity, range of motion, and isokinetic and KT-1000 testing. Brace use and postoperative level of competition were also recorded. In addition, the patients completed a subjective assessment questionnaire rating pain, swelling, and stability. They also rated overall activity level, and any changes in their ability to do the activities tested: walk, climb stairs, run, jump, or twist. Our results indicate that proper reconstruction of the anterior cruciate ligament, in conjunction with nonoperative management of tears of the medial collateral ligament in combined anterior cruciate ligament-medial collateral ligament injuries, can given excellent stability and good to excellent functional outcome in patients with combined anterior cruciate ligament-medial collateral ligament injuries. PMID- 1636859 TI - Evaluation of ultrasonography as a diagnostic technique in the assessment of rotator cuff tendon tears. AB - In this study we assessed the clinical usefulness of ultrasonography as a modality in the diagnosis of rotator cuff tears. One hundred twenty patients with preoperative ultrasonography were analyzed by diagnostic arthroscopy to evaluate rotator cuff integrity. Two groups, 61 patients with a positive ultrasonogram and 59 patients with a negative ultrasonogram, were analyzed. The 61 patients with a positive ultrasonogram preoperatively were found to have 42 full-thickness tears and 19 partial-thickness tears. Diagnostic arthroscopy confirmed a sensitivity of 95% for the full-thickness tears and 41% for the partial-thickness tears. In the 59 patients with negative ultrasonography, the specificity for full-thickness tears was 93% and in the 19 partial-thickness tears it was 91%. Our conclusion is that ultrasonography is an effective modality for the assessment of full thickness tears, but not partial-thickness tears. PMID- 1636860 TI - Stress changes of the distal radial growth plate. A radiographic survey and review of the literature. AB - We conducted a radiographic survey to determine skeletal age and the nature and prevalence of stress-related changes affecting the distal radial growth plate in 60 young competitive gymnasts (39 females, 21 males). Comparison of results for chronological and skeletal age revealed a significant delay in maturation for girls (P less than 0.001). Radiographic evaluation revealed 5 gymnasts (4 girls and 1 boy) with stress-related changes of the left wrist, and four of these were considered to be minimal. These results, in conjunction with our previous findings and the review of related literature, reveal three important observations. First, the widening and irregularities of the distal radial physis that we described previously appear to be the first in a spectrum of abnormal changes secondary to overuse and probably represent a stress fracture of the distal radial growth plate. The radiographic changes associated with this injury are not the normal adaptive changes seen in young, competitive gymnasts. Secondly, more serious long-term abnormality may result even though the injury may initially resemble a Salter-Harris type I or II stress fracture. Long-term complications may include symmetrical or asymmetrical retardation or halted growth at the affected site, positive ulnar variance, and associated pathoanatomic sequelae. Thirdly, the incidence of distal radial growth plate stress injury remains unclear; we recommend a further, large-scale prospective epidemiologic study involving both male and female gymnasts. We urge that physicians and other health professionals associated with gymnastics clubs educate coaches about the possibility of significant injury to the distal radial physis, risk factors, and suggested preventive measures. PMID- 1636861 TI - Anterior-posterior and rotational displacement of the tibia elicited by quadriceps contraction. AB - The anterior-posterior displacement and rotation of the tibia elicited by isolated loading of the quadriceps muscle was determined as a function of joint angle and muscle load using a computerized radiographic technique. Data collected from 12 fresh-frozen cadaveric knees demonstrated that quadriceps contraction can result in significant (less than 7 mm) anterior displacement of the tibia in the range of 0 degrees to 80 degrees of flexion, and a mild (less than 2 mm) posterior displacement in the range of 80 degrees to 120 degrees of flexion. Peak anterior displacement of 6.3 mm was observed at 30 degrees of flexion under a 12 kg load in the quadriceps, while a constant 1.5 mm posterior displacement was observed throughout flexion angles exceeding 80 degrees. It was further shown that the magnitude of the anterior displacement increased nonlinearly as the quadriceps force increased. Loading of the quadriceps also resulted in internal rotation of the tibia in the range of 0 degrees to 90 degrees of flexion, and in external rotation of the tibia in the range of 90 degrees to 120 degrees. Peak internal rotation of 7 degrees was observed at 15 degrees of flexion and a peak external rotation of 1 degrees was detected at 120 degrees of flexion. Larger quadriceps load resulted in larger rotation. We concluded that quadriceps contraction during knee extension has direct impact on anterior displacement and rotation of the tibia and therefore on anterior cruciate ligament stress, increasing it as the muscle's force is increased during knee extension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636862 TI - An electromyographic analysis of the elbow in normal and injured pitchers with medial collateral ligament insufficiency. AB - Electromyography and high-speed film were used to examine the muscle activity in the elbows of pitchers with medial collateral ligament insufficiency compared to the activity in uninjured elbows. Ten competitive baseball pitchers with medial collateral insufficiency and 30 uninjured competitive pitchers were tested while throwing the fastball and the curveball. The extensor carpi radialis brevis and longus in the injured pitchers showed greater activity than in the uninjured pitchers for both pitches. The triceps, flexor carpi radialis, and pronator teres all showed less activity in the injured pitchers during the fastball, but only the triceps had less activity during the curveball. The differences were seen during the late cocking and acceleration phases, which place the greatest stress on the medial collateral ligament. If the flexor carpi radialis and pronator teres were substituting for the deficient medial collateral ligament and functioning as dynamic stabilizers, one would expect enhanced muscle activity. However, the opposite was found. This pattern of asynchronous muscle action with medial collateral ligament injury may predispose the joint to further injury. The muscular differences seen are critical to the understanding of the pathomechanics of patients with medial collateral ligament deficiency, and provide a basis for rehabilitation. PMID- 1636863 TI - European soccer injuries. A prospective epidemiologic and socioeconomic study. AB - In 1 year, 715 patients with soccer injuries were registered and treated in the emergency department of Randers City Hospital. We did a prospective study of these patients using a questionnaire to determine the most common locations, types, mechanisms, and treatments of injury. Financial costs for society and the individual were also examined. Forty-nine percent of the injuries were to the joints; sprains and contusions were the most common types of injury, accounting for 46% and 25%, respectively. The majority of patients (64% of the men and 58% of the women) were injured during physical contact with another player. Most (63%) of the patients were treated in the emergency department and then released. Thirty-one percent had to be absent from work, but only 8% of the patients had a loss of income because of their injury. The average amount of work time lost was 5 days. PMID- 1636864 TI - Shoulder torque changes in the swimming athlete. AB - Torque production was assessed in the shoulders of competitive men and women swimmers for the motions of abduction, adduction, and external and internal rotation. Testing was performed on the Cybex II dynamometer and the results were compared to controls. In addition, the ratios of torque development for adduction:abduction and external rotation:internal rotation were evaluated. The results demonstrated a statistically significant increase in torque production in swimmers for most motions tested. Statistically significant ratio shifts were also noted. The ratio of adduction:abduction increased and that for external rotation:internal rotation decreased. We think these shifts in the torque ratios in swimmers' shoulders resulted from sport-specific repetitive activity that emphasizes adduction and internal rotation. PMID- 1636865 TI - Strength testing after third-degree acromioclavicular dislocations. AB - Twenty male patients with a grade III acromioclavicular joint dislocation were evaluated more than 2 years after their injury; the average followup was 4.5 years. Strength testing was performed with a Cybex II dynamometer in three planes evaluating flexion, extension, internal rotation, external rotation, abduction, and adduction at 60 and 120 deg/sec. Subjective complaints were minor and neither daily activities nor athletic participation were impaired. Objectively, only one patient had tenderness over the acromioclavicular joint. All patients had full motion and negative impingement signs. Strength testing with the Cybex II dynamometer showed no significant difference (P less than 0.05) between the injured and uninjured shoulder for strength in internal rotation, external rotation, abduction, adduction, extension, or flexion at speeds of 60 and 120 deg/sec. This study shows that the strength of the shoulder is not significantly affected by conservative treatment of grade III acromioclavicular dislocations. Conservative treatment results in minimal or no functional deficit. The authors recommend that grade III acromioclavicular dislocations be treated nonoperatively. PMID- 1636866 TI - Magnetic resonance imaging evaluation of the patellar tendon after use of its central one-third for anterior cruciate ligament reconstruction. AB - Magnetic resonance imaging was used to evaluate the remaining patellar tendon after its central one-third had been harvested for anterior cruciate ligament reconstruction. Twenty patients were studied at either 6 weeks, 4, 6, 9, or 18 months postoperatively. The average thickness, width, cross-sectional area, and signal intensity of the operated and contralateral non-operated tendons were calculated and compared for each magnetic resonance imaging scan. A significant increase in the thickness was noted at all periods of followup, but no change in width occurred despite the defect being closed at the time of surgery. High signal intensity was present in the early periods, which signified edema and scar tissue. Signal intensity decreased at subsequent follow-up periods until at 18 months the operated tendon appeared normal. These findings indicate that the patellar tendon has the potential to regenerate and remodel in the postoperative period. PMID- 1636867 TI - Allograft anterior cruciate ligament reconstruction in a sheep model. The effect of synthetic augmentation. AB - The purpose of this study was to assess the effect of synthetic augmentation of a bone-patellar tendon-bone allograft on the basis of biomechanical, morphologic, and histologic evaluation. The anterior cruciate ligament was reconstructed in the left knee of 66 adult sheep. Half the knees received bone-patellar tendon bone grafts alone, while the other half were augmented. All of the knees, including the contralateral controls, had gross and histologic examination, hydroxyproline assay for collagen content, and biomechanical testing in groups at 0, 4, 16, and 52 weeks postoperatively. Biomechanical testing included anteroposterior translation, ultimate tensile strength, energy to failure, stiffness, and mode of failure. Eight fresh bone-patellar tendon-bone allografts were compared to eight cryopreserved bone-patellar tendon-bone allografts for baseline data on the effects of the cryopreservation. Cryopreservation did not have any effect on graft characteristics. Gross and histologic examination did not reveal any significant difference between the augmented and nonaugmented groups at any of the time periods. In addition, hydroxyproline content of the allograft was not altered by augmentation throughout the study period. Biomechanical laboratory evaluation demonstrated the augmented group had significantly reduced anteroposterior translation (P less than 0.05) at 52 weeks compared to the nonaugmented group. The ultimate tensile strength was significantly higher (P less than 0.05) in the augmented group at 4 weeks, but at 52 weeks both groups had attained only 50% of the normal anterior cruciate ligament strength. Stiffness and energy to failure were similar in both groups at all time periods. From the results of this study, synthetic augmentation appears to improve initial strength and prevent late allograft laxity while allowing normal remodeling processes to occur in the bone-patellar tendon-bone allograft anterior cruciate ligament reconstruction. PMID- 1636868 TI - Avulsion fracture of the medial epicondyle caused by arm wrestling. AB - Fractures occurring in teenagers during arm wrestling usually involve the distal humerus and appear as a fracture of the medial epicondyle. We studied eight male patients, aged 13 to 15 years, with such fractures. All fractures involved the right hand and occurred while the patients were in the final stages of winning a match in a formal competition. Three fractures occurred during an official competition and the other five occurred during a match between friends. One patient suffered from ulnar nerve paresis that eventually recovered spontaneously. All of the patients were immobilized for 10 to 21 days, and progressed gradually to motion of the elbow. At 1-year followup, clinical and functional results were satisfying. Therefore, we recommend conservative management for fractures of the medial epicondyle sustained during arm wrestling. PMID- 1636869 TI - Measurements of length and tension patterns during reconstruction of the posterior cruciate ligament. AB - The twofold purpose of this study was to develop an intraoperative technique to assess isometric positioning of posterior cruciate ligament grafts and to demonstrate the rationale for postoperative immobilization of the knee in full extension after a posterior cruciate ligament reconstruction. Multiple femoral fixation sites were selected on the medial intercondylar notch and the posterior cruciate ligament substitute was assessed for changes in length and tension at each of these sites during knee flexion from 0 degree to 120 degrees. The most isometric and isotonic femoral fixation site was localized over a small area slightly distal to the center of the medial intercondylar notch surface. This isometric point can be identified intraoperatively using recognizable surface markers within the knee. When a posterior stress was applied to the proximal tibia, the posterior cruciate ligament substitute showed the least increase in tension and length when the knee was locked in full extension for all of the potential femoral attachment sites assessed. This suggests that postoperative immobilization should be maintained in full extension to limit the stress placed on the posterior cruciate ligament reconstruction. PMID- 1636870 TI - Isolated musculocutaneous nerve injury complicating closed fracture of the clavicle. A case report. PMID- 1636871 TI - Scapular fractures in professional football players. PMID- 1636872 TI - Avulsion of the pectoralis major tendon. PMID- 1636873 TI - The efficacy of halofantrine in the treatment of acute malaria in nonimmune travelers. AB - A multicenter prospective trial was performed to investigate the efficacy and the tolerability of halofantrine in nonimmune patients with malaria imported from areas with drug-resistant falciparum parasites (mainly Africa). Forty-five of the 74 subjects were treated with a one-day regimen (3 x 500 mg) of halofantrine, and the other 29 received the same regimen with an additional treatment on day 7. In the second group, a 100% efficacy rate was demonstrated, but in the group receiving the one-day regimen, four recrudescences were observed in patients with falciparum malaria. Only five mild adverse reactions were seen, which disappeared spontaneously after the end of the treatment. We conclude that halofantrine is highly effective in curing malaria in nonimmune subjects. The treatment scheme for such persons should include an additional treatment on day 7 for nonimmune individuals. This drug was well tolerated in our patients, indicating that halofantrine will be useful in the treatment of multidrug-resistant malaria in nonimmune persons. PMID- 1636874 TI - Intestinal capillariasis (Capillaria philippinensis) acquired in Indonesia: a case report. AB - We report a case of intestinal capillariasis in a 32-year-old Italian man. After he made a trip to Indonesia that lasted approximately one month, he developed heartburn, abdominal pain, irregular bowel movements, headache, fatigue, weight loss, low-grade fever, and severe itching. The diagnosis was provided by the recovery of Capillaria philippinensis eggs in the stool. Treatment with oral albendazole, 200 mg twice a day for 21 days, resulted in clinical and parasitologic cure. This is the first report of C. philippinensis infection acquired in Indonesia. PMID- 1636875 TI - Parasite-specific IgE and IgG levels in the serum and pleural effusion of paragonimiasis westermani patients. AB - In seven patients with paragonimiasis westermani, parasite-specific IgE and IgG levels in sera and pleural effusion were determined by an enzyme-linked immunosorbent assay (ELISA). The sensitivity to adult excretory-secretory (E-S) antigen was compared with the sensitivity to whole worm extract antigen, and the former was more sensitive in both an IgE-ELISA and IgG-ELISA. Both parasite specific IgE and IgG could be detected by ELISA at levels much higher than those in control subjects using E-S antigen. When specific IgE and IgG levels in sera and pleural effusion of individual patients were compared, the latter had higher values. The difference between levels of specific IgE in pleural effusion and serum did not correlate with that of specific IgG. These results indicate that specific IgE and IgG antibodies form locally, i.e., in the lung, and that pleural effusions from patients with paragonimiasis are more suitable than serum for immunodiagnosis. PMID- 1636876 TI - Quinine with tetracycline for the treatment of drug-resistant falciparum malaria in Thailand. AB - Reports of deteriorating quinine efficacy prompted us to investigate the ability of quinine-tetracycline to clear parasites and fever from patients with multiple drug-resistant Plasmodium falciparum infections. Past and present treatment results were compared at two study sites along the Thai-Cambodian border. In northeastern Thailand, quinine-tetracycline cleared parasites more quickly in 1990 than in 1987 (mean 3.4 and 4.0 days, respectively; P = 0.006). In southeastern Thailand, there were no significant differences between 1990 (n = 26) and 1981-1983 (n = 42) in the time taken to clear either parasites (median 96 and 93 hr, respectively; P = 0.35) or fever (mean 74 and 66 hr, respectively; P = 0.30). In vitro drug sensitivity testing revealed a two-fold decrease in susceptibility to quinine between 1983 and 1990 in isolates from the southeastern Thai-Cambodian border (mean inhibitory concentration 166 ng/ml and 320 ng/ml, respectively; P less than 0.001). We conclude that oral quinine-tetracycline continues to reliably clear parasites and fever from falciparum malaria patients infected in eastern Thailand. Periodic re-evaluations are warranted, however, since the decrease in vitro susceptibility to quinine may be followed by an in vivo decay in the treatment response. PMID- 1636877 TI - Emergence of multidrug-resistant Plasmodium falciparum in Thailand: in vitro tracking. AB - Mefloquine was introduced into Thailand in 1985 for the treatment of Plasmodium falciparum infection. Recently, clinical failure of mefloquine was observed in southeastern Thailand, where an epidemic of falciparum malaria occurred. Beginning in 1984 and continuing until 1989, in vitro monitoring of P. falciparum isolates from Borai, a border district in the southeastern part of the country, showed a progressive decrease in mefloquine sensitivity until 1989; in 1990, the degree and prevalence of resistance accelerated. A similar pattern of resistance was observed for halofantrine, an antimalarial drug not yet commercially available in Thailand. In vitro sensitivity patterns of mefloquine and halofantrine elsewhere in the country remained relatively unchanged. These observations suggest a serious deterioration in available drugs for the treatment of falciparum malaria in southeastern Thailand that is predicted to spread throughout the country and Southeast Asia. PMID- 1636878 TI - Epidemiology of giardiasis in Wisconsin: increasing incidence of reported cases and unexplained seasonal trends. AB - Giardia lamblia is the most commonly reported enteric pathogen in Wisconsin. Since giardiasis became a notifiable disease, the annual number of cases reported to the Wisconsin Division of Health has increased more than 20-fold, from 2.2 cases per 100,000 population in 1981 to 49.1 cases per 100,000 population in 1988. To better understand the nature of this increasing trend, we reviewed records of G. lamblia infections reported to the Wisconsin Division of Health from 1981 to 1988. Although the increase in reported cases was a general phenomenon that was not limited to a few high-risk groups, the highest annual incidence and greatest increase occurred in children 1-4 years old; 34% of the cases in this age group occurred in children who attended day care centers. A remarkably consistent late summer (August) increase was observed across all demographic and risk groups, suggesting that G. lamblia may be more common in the environment during late summer, or that risk factors for transmission may differ during these months. Additional studies are needed to further explain the increasing incidence and seasonal nature of reported giardiasis and to identify opportunities for prevention. PMID- 1636879 TI - Vectorial transmission of Trypanosoma cruzi: an experimental field study with susceptible and immunized hosts. AB - The dynamics of vectorial transmission of Trypanosoma cruzi and the level of host (guinea pigs) protection after immunization with attenuated parasites (TCC strain) was studied under natural climatic conditions in an endemic region of northern Argentina. The experimental design included two guinea pig corrals isolated by mosquito netting. One (controls) had 17 healthy and susceptible adult guinea pigs. The other had 19 guinea pigs immunized with attenuated T. cruzi TCC strain. Each corral was colonized in April 1988 with equal-sized populations of Triatoma infestans naturally infected by T. cruzi. To evaluate relevant variables in the natural transmission of Chagas' disease, corrals were sampled in both winter and late spring to assess vector populations, and to carry out parasitologic studies on both vertebrate and invertebrate hosts. In both corrals, vector density decreased in winter and reached a maximum in the hot season. The vector infection rate was very high (greater than 50%) throughout the experiment. Vector infectivity increased with temperature and vector age, but did not differ between the experimental and control corrals. The vector-host contact rate showed a close relationship with temperature, although a very high vector density decreased this rate, even with high ambient temperatures. Initial infections by T. cruzi occurred among guinea pigs only during the hot season. Vectorial transmission risk was estimated from the total number of bug bites per day, the proportion of infected bugs, and the daily incidence in the guinea pig population. During the hot season, this risk was 6.84 x 10(-4) in the control group and 1.82 x 10(-4) in the immunized group. PMID- 1636880 TI - Lymphocytic choriomeningitis virus infection and house mouse (Mus musculus) distribution in urban Baltimore. AB - Four hundred eighty house mice (Mus musculus) were trapped primarily from urban sites in Baltimore, Maryland from 1984 to 1989 and tested for antibody to lymphocytic choriomeningitis virus (LCMV). The majority of mice (95%) were trapped in residences at two city locations (n = 260), or in an urban park (n = 196); five additional sites were sampled. Overall, 9.0% of the mice were LCMV antibody positive and infected animals were obtained from six of eight sites, including all three of the primary city sites, where the prevalence varied significantly (3.9-13.4%). The location with the highest prevalence was an inner city residential site where positive mice were found significantly clustered within blocks and households. In this location, LCMV antibody prevalence was also significantly correlated with estimates of mouse density within individual blocks. The focal nature of LCMV infection in house mice may result from contact or vertical transmission of virus in conjunction with the highly structured social system of mice, which promotes inbreeding and limited dispersal. PMID- 1636881 TI - A cluster of Coxiella burnetii infections associated with exposure to vaccinated goats and their unpasteurized dairy products. AB - An outbreak of Q fever occurred among patients and staff of a psychiatric institution in southern France. Some of the patients and staff left the institution daily to work on a farm where goats were raised for raw milk and cheese production. The goats had all been vaccinated annually with a commercial vaccine containing phase II Coxiella burnetii antigen. A serologic survey revealed that 40 (66%) of the 61 patients and staff had elevated titers to C. burnetii. Seropositive persons were more likely to report an acute illness (P = 0.001), fever (P = 0.04), weakness (P = 0.04), arthralgia (P = 0.04), and headaches (P = 0.06) in the preceding year than were seronegative persons. Seropositivity rates were significantly higher among persons who worked on the farm and consumed unpasteurized milk products (69% [22 of 32]; P = 0.007), those who only had worked on the farm (75% [9 of 12]; P = 0.009), and those who only had consumed unpasteurized milk products (75% [9 of 12]; P = 0.009), compared with those who had not worked with the goats or consumed unpasteurized milk products (0 of 5). Despite vaccination against Q fever, no antibodies to C. burnetii were detectable in 17 (59%) of 29 goats. All 12 seropositive goats had antibodies to both phase I and phase II antigens, indicating that they were naturally infected, and two of three goats examined were shedding C. burnetii in their milk. Vaccination of this herd did not prevent the outbreak and might have increased shedding of C. burnetii in the dairy products. PMID- 1636882 TI - Ookinete rates in Afrotropical anopheline mosquitoes as a measure of human malaria infectiousness. AB - Anopheles gambiae s.1. and An. funestus were sampled for Plasmodium spp. ookinetes in two P. falciparum-endemic sites in western Kenya. Since the ookinete is a transitional stage of short duration, occurring after fertilization and before oocyst development, only females in the half-gravid and gravid stages of blood digestion were examined. Preparations of homogenized midguts were spotted onto microslides and examined microscopically after staining with Giemsa. Overall, ookinetes were detected in 4.4% of 1,079 anophelines examined over an eight-month period. Anopheles funestus had higher ookinete rates than An. gambiae s.1., and ookinete rates were higher in half-gravid than in gravid An. gambiae s.1. Geometric mean numbers of ookinetes per infected female were less than five for each species at the two sites, and the maximum number observed was only 12. The low frequencies and numbers of ookinetes were sufficient to produce sporozoite rates of 4-18% in the vector populations. The intense transmission of P. falciparum in these two sites is maintained by anthropophilic vectors where only one in 23 blood meals initiates an infection of generally less than five ookinetes. Relationships between human malaria infectiousness and vector infectivity are dependent upon the high efficiency of the developmental transition from the ookinete to the subsequent oocyst and sporozoite stages. PMID- 1636883 TI - Epidemiologic investigation of an outbreak of cutaneous leishmaniasis in a defined geographic focus of transmission. AB - An outbreak of cutaneous leishmaniasis occurred in a unit of 608 Puerto Rican national guardsmen conducting jungle warfare training in the Panama Canal Area in July 1984. An epidemiologic investigation of reported nonhealing, ulcerating skin lesions was conducted among 540 (89%) unit members in November and December 1984. Fifteen (88%) of 17 individuals with chronic, ulcerating skin lesions were confirmed as cases of cutaneous leishmaniasis by culture or histopathology. Twelve cases yielded positive Leishmania cultures, identified as L. braziliensis panamensis by cellulose acetate electrophoresis. Evaluation of different diagnostic techniques revealed that direct examination of tissues by Giemsa stained histological examination was the most sensitive test (87% sensitivity), with an indirect immunofluorescent antibody test being rather insensitive (67%). All but one of the confirmed cases operated in small units that trained and slept overnight at a mortar firing site for a period of three days, yielding a site specific attack rate of 22% (14 of 64). This contrasted with a much lower attack rate of 0.2% (1 of 476), experienced by unit members who trained at other locations during the same time frame (P less than 0.001). The median incubation period calculated from day of arrival at the mortar firing site was 17 days (range 2-78) for the 15 confirmed cases. Available personal protection methods, such as the use of insect repellents, were not appropriately implemented by unit personnel and thus, were not found to effectively protect against Leishmania infection. This is the largest reported outbreak of cutaneous leishmaniasis in military personnel associated with a single geographic focus of infection and contrasts with the usual sporadic disease experience in Panama. PMID- 1636884 TI - Clustering of host-seeking nymphal deer ticks (Ixodes dammini) infected by Lyme disease spirochetes (Borrelia burgdorferi). AB - In areas where the agent of Lyme disease is intensely enzootic, the mouse reservoirs may be universally infected. Because a large proportion of the vector tick population appears to feed upon these hosts, the prevalence of infection in the vectors should approach 100%. However, infection in host-seeking nymphal ticks in nature rarely exceeds 40%. To help reconcile this apparent paradox, we examined whether estimates of prevalence might differ if we did not assume that infected ticks are randomly or uniformly distributed within a site. Nymphal Ixodes dammini were collected by dragging a series of 10-meter replicates within an intensely enzootic site. Estimates of the prevalence of spirochetal infection, based upon the monthly means of individual 10-meter collections, were then compared with estimates derived by pooling all samples. Host-seeking ticks tended to cluster. The Lyme disease spirochete was present in 15.6% of 469 pooled ticks. When the prevalence estimate was based solely on ticks in clusters that contained one or more infected ticks, however, at least 50% of the ticks were infected. We conclude that nymphal deer ticks infected by Lyme disease spirochetes tend to aggregate spatially in nature, and that prevalence estimates based upon a mean value for pools may be misleading. PMID- 1636885 TI - Schistosomiasis and the Dogon country (Mali) AB - A previously unknown area of schistosomiasis transmission is reported based on findings from a travelers' clinic in Barcelona. Three species of Schistosoma (S. haematobium, S. mansoni, and S. intercalatum) were diagnosed in a cluster of 43 patients who had been swimming in the Bandiagara and Bankas districts of Mali, where the Dogon people live. Three villages in the Bankas district appear to harbor these three species. The transmission potential of such a focus in this area is outlined. The travelers involved had little or no information on the risks of contracting schistosomiasis in that area. Obtaining a traveler's history, including accurate geographic data, is shown to be a crucial asset for improving epidemiologic research. PMID- 1636886 TI - Characterization of the heat-shock response of Trichomonas vaginalis. AB - The heat-shock response induced in Trichomonas vaginalis by exposure to various incubation temperatures was traced by metabolic labeling and monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. Increasing the incubation temperature from 37 degrees C to 43 degrees C depressed normal protein production and enhanced synthesis of heat-shock proteins (hsp). Smaller increases in incubation temperature resulted in little change in protein synthesis, whereas larger temperature increases inhibited protein synthesis. The hsp produced by T. vaginalis included molecules with approximate molecular masses of 85, 78, 66, 61, 35-31, 20-15, and 12 kD. Trichomonas vaginalis switched to hsp synthesis gradually. Full conversion to hsp production occurred within 60-90 min after the initiation of the 43 degrees C stress. The period of synthesis was different for individual hsp, suggesting independent regulation of hsp production. Four strains of freshly reinitiated and culture-adapted (extended in vitro culture) T. vaginalis synthesized the 85-, 78-, and 66-kD hsp, but varied in the synthesis of the 61-, 35-, 34-, 32-, and 31-kD molecules. Culture adaptation affected the heat-shock response of two of the four strains tested. PMID- 1636887 TI - Nucleoside transporters in Leishmania major: diversity in adenosine transporter expression or function in different strains. AB - Cytotoxic nucleoside derivatives may become useful in the treatment of parasitic infections. As part of our drug development studies, the effect of a number of nucleosides (100 microM) on the cellular transport of 3H-adenosine and 3H-inosine (each at 1 microM) in promastigotes from four Leishmania major strains was investigated. When 3H-inosine was used as permeant, all strains exhibited essentially the same inhibition profile, with unlabeled inosine, guanosine, formycin B, and 3'-deoxyinosine being strongly inhibitory, and adenosine-related compounds such as 2'-deoxyadenosine and tubercidin being inactive. However, when 3H-adenosine was used as permeant, considerable differences in the inhibition profiles were noted among strains. Thus, both inosine transporter-selective nucleosides such as inosine and guanosine and adenosine transporter-selective nucleosides such as 2'-deoxyadenosine and tubercidin showed variable activity as inhibitors of 3H-adenosine transport in different strains. These observations indicated that an adenosine transporter was variably expressed in different strains, and that inhibition profiles for adenosine transport indicated cellular entry via both the inosine and adenosine transporters. The existence of different types of adenosine transporters as an alternative explanation could not be ruled out. The apparent uniform expression of an inosine transporter among different species and strains of Leishmania suggests that inosine derivatives may be useful as anti-leishmanial drugs. PMID- 1636889 TI - Percutaneous endoscopic gastrostomy or jejunostomy and the incidence of aspiration in 79 patients. AB - Percutaneous endoscopic gastrostomy (PEG) and percutaneous endoscopic jejunostomy (PEJ) are well-accepted procedures for long-term enteral alimentation. PEG has replaced surgical gastrostomy at many institutions because of its safety and ease. This study was undertaken to evaluate the indications for PEG and PEJ, as well as their success rates, complications with special attention to aspiration, and long-term follow-up. We were specifically interested in reviewing the problem of aspiration in patients with PEG and PEJ. A retrospective review of 79 patients at Brooke Army Medical Center over a 3-year period was done. PEG or PEJ was successful in 79 of 81 patients (97%). The most common indications were neurologic disorders in 46 patients (58%) and cancer in 20 (25.3%). Complications other than aspiration occurred in 11 patients (14%). Aspiration occurred in nine patients after PEG or PEJ (11.4%); six patients had experienced aspiration prior to PEG or PEJ. Six patients had a jejunostomy tube placed through the PEG for prevention of aspiration, and three died of continued aspiration. We conclude that aspiration is not prevented by PEJ, continues to be a major problem after PEJ, and becomes manifest for the first time after PEG. PMID- 1636888 TI - Clinical utility of open lung biopsy for undiagnosed pulmonary infiltrates. AB - Open lung biopsy (OLB) is often performed as the definitive diagnostic procedure in patients with undiagnosed pulmonary infiltrates, but controversy exists as to the clinical utility of this practice. A retrospective review of 50 consecutive patients who underwent OLB for undiagnosed pulmonary infiltrates was done to assess the diagnostic value as well as the frequency with which these results affected therapy and mortality. Histologic tissue diagnoses were obtained in all patients. Specific pathologic diagnoses were obtained in 56% of patients, nonspecific in 44%. Lobar or lateralized infiltrates were more likely to yield a specific diagnosis (87%) than diffuse, bilateral infiltrates (42%). Thirty-four patients (68%) had previously had a nondiagnostic transbronchial biopsy; 58% of these patients had a specific diagnosis established by OLB. Twelve patients (24%) were in acute respiratory failure at the time of OLB; this group had a 50% mortality rate as compared with only 2.6% for patients not in acute respiratory failure (p less than 0.01). Therapy was altered (new specific or nonspecific treatment initiated or therapy withdrawn) in 78% of patients undergoing OLB. Thirty-day in-hospital survival was significantly higher in patients for whom either specific or nonspecific therapy was indicated and initiated versus those in whom no therapy was initiated or all therapy was withdrawn (mortality: 5.5% versus 35.7%; p = 0.01). Mortality was not related to the presence of immunosuppression or to the finding of a specific diagnosis. The overall mortality rate of 14% in this series compares favorably with mortality rates found in similar series, reflecting differences in patient populations and possibly the timing of intervention. OLB remains a clinically valuable diagnostic tool in selected patients. PMID- 1636890 TI - Simulation of blood flow in microgravity. AB - Knowledge of venous, capillary, and arterial blood flow in microgravity is required to modify hemostatic techniques for control of bleeding in traumatic injuries or surgical procedures in space. To simulate human arterial, venous, and capillary bleeding, fresh whole bovine blood was injected by two operators at calculated flow rates (3.5, 7, and 14 mL for venous and 14 and 28 mL for arterial) in 10 seconds with empirical controls in a lucent glove box during zero gravity parabolic flight on NASA's KC-135 aircraft. A pig's foot was used to mimic capillary bleeding. Hemostasis with sponges and laerdal suction was evaluated by video and still photography. Evaluations of the arterial and venous bleeding were conducted at 3 rates x 3 parabolas, and capillary bleeding was evaluated with 5 parabolas x 2 methods (pig's foot and sponge). Influenced by surface tension, the slow venous bleeding coated syringe surfaces and formed a dome over the skin laceration bleeding site. Arterial and venous bleeders broke into uniform spheres with low-velocity spheres bouncing off an absorbent pad and suction tip. Conventional dabbing with gauze fragmented blood into small spheres. Capillary oozing was better controlled by "wicking" up blood with gauze. Repeated arterial bleeding opacified the glove box wall. This stimulation demonstrated unique characteristics of extracorporeal blood flow and inadequacies of common methods of hemostasis in microgravity. PMID- 1636891 TI - Biliary reconstruction in benign postoperative stricture with transhepatic tubes. AB - This study reports our experience with 31 patients who underwent biliary reconstructions due to iatrogenic lesions of the main biliary tract. The technique of Hepp and Couinaud, associated with the use of transhepatic Silastic tubes, was utilized in 90% of the patients, and the mucosal graft was employed in only three patients. The recommended time for keeping the transhepatic tube in place was 6 months. In order to prevent subphrenic fluid collection between the tube exit orifice in the hepatic parenchyma and the abdominal wall, the tubes were protected with a Penrose drain over the course of their use. This tactic appeared effective. The immediate postoperative mortality was 9%, and the long term results, with a mean follow-up period of 44 months, were considered good in 92% of the patients who survived surgery. PMID- 1636892 TI - Polytetrafluoroethylene in above-knee arterial bypass surgery for critical ischemia. AB - Seventy-one consecutive above-knee polytetrafluoroethylene (PTFE) femoropopliteal arterial bypasses performed between 1981 and 1989 for critical ischemia were followed prospectively to determine graft patency and limb salvage. Cumulative graft patency and limb salvage rates were calculated by life table analysis. Graft patency was 80%, 68%, 55%, 39%, and 39%, and limb salvage 97%, 87%, 84%, 77%, and 77% at 1, 2, 3, 4, and 5 years, respectively. Twenty-nine grafts have occluded with re-emergence of critical ischemia in 14, treated by 5 amputations and 9 reconstructions using autogenous saphenous vein (ASV) in 6 and PTFE in 3. These favorable results are not as good in terms of primary patency as those reported with ASV, but good limb salvage, good early patency, ease of use, and preservation of the saphenous vein for use later have encouraged us toward primary use of PTFE in selected patients. This experience strongly questions the wisdom of an "all autogenous" policy for reconstruction at this level. PMID- 1636894 TI - Molecular biology: an overview. AB - An overview of molecular biology is presented for the practicing surgeon. Definitions of the constructs and activity of DNA, RNA, and protein synthesis are defined. These principles are illustrated in their use in recombinant DNA technologies. A glossary is provided for the terms utilized. PMID- 1636893 TI - 31P-NMR evaluation of postischemia renal ATP and pH levels after ATP-MgCl2 treatment in rabbits. AB - Phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopy was used to measure adenosine triphosphate (ATP) concentration and pH in vivo in rabbits subjected to a 40-minute period of unilateral renal ischemia to determine the effect of infusing ATP-magnesium chloride (MgCl2, 100 mumol/kg) versus saline at the initiation of reperfusion. Data were compared initially by analysis of variance and then analyzed further using a general linear model with covariate adjustment. ATP-MgCl2-treated animals did not have higher ATP levels during recovery but did have significantly higher renal blood flow (p less than 0.05), a significantly decreased rate of recovery from acidosis (p less than 0.05), and significantly higher urinary output (p less than 0.01) than saline-treated animals during the recovery period. Therefore, treatment with ATP-MgCl2 improves postischemic functional parameters in this model of moderate injury without functioning as a direct source of ATP or its precursors. These data add support to the emerging concept that intracellular acidosis protects cells from reperfusion injury. PMID- 1636895 TI - An update on incision for ilioinguinal lymph node dissection. AB - The wound morbidity after ilioinguinal lymph node dissections can be significantly reduced by precise planning of both the incision and the extent of flap elevation. Flap elevation extends no farther than the edges of the quadrilateral block of Anson, and exposure is best obtained with a bipedicle incision with broad-based pedicles. The broad bases ensure the greatest possibility for the sustentation of the flaps by the remaining microcirculation. All suction drains are placed far laterally, not through the base of any flaps, to avoid the high bacterial count on the skin of the groin, genitals, perineum, and anus. Closure is undertaken with a running suture, which allows for a seal that will facilitate suction. Suction continues until drainage is less than 25 mL/d. PMID- 1636896 TI - Direct septum transversum incision to replace circumferential diaphragmatic incision in operations on the cardia. AB - Application of a simple anatomic approach to lesions of the cardia, both benign and malignant, in consecutive patients has demonstrated an excellent exposure with the same flexibility as the standard, circumferential, diaphragmatic, and abdominal incision used for the past 50 years. The technical details of the procedure and its application are described, along with the pertinent embryology, anatomy, and physiology that led to this approach. PMID- 1636897 TI - A technique for rapid closure of traumatic small intestine perforations without resection. AB - Small bowel perforation after blunt trauma is frequently associated with other intra-abdominal injuries. Typically, large luminal defects are encountered after blunt trauma that cannot be closed primarily without subsequent luminal compromise, necessitating formal resection with primary anastomosis. We describe a safe, rapid, and effective method by which traumatic small bowel perforations may be closed without resection using readily available gastrointestinal stapling devices. The speed of the closure allows for expedient management of associated injuries without fear of continued enteric spillage. No mesenteric resection or closure is needed, obviating the possibility of internal hernias. PMID- 1636898 TI - Nasopharyngeal brachytherapy with access via a transpalatal flap. AB - We used a posteriorly based transpalatal flap for interstitial nasopharyngeal brachytherapy in five patients with nasopharyngeal carcinoma. All of these implants were done with iodine 125 seeds. The disease in three of five patients has been controlled locally for 27, 30, and 40 months, respectively. Two patients experienced local failure and died. There have been no palatal healing problems despite high doses of previous radiation in all of our patients. No palatal incompetence has been seen. This technique appears safe and should be considered for discrete lesions of the high posterior or superior nasopharynx that cannot be approached by less invasive methods. PMID- 1636899 TI - Absence of colorectal cancer metastasis to the cirrhotic liver. AB - Hepatic metastasis of colorectal cancer was found in 40 (16%) of 250 patients with colorectal cancer treated in our department during the past 5 years. Liver cirrhosis was not found among the 40 patients with metastases (16%) but was present in 46 (21.9%) of the 210 nonmetastatic patients, with a significant difference between the two groups (p less than 0.001). The rate of patients who were positive for hepatitis B surface antibody was 10% in the metastatic group and 34.3% in the nonmetastatic group, with a significant difference (p less than 0.01). These findings suggest that colorectal cancer does not metastasize to the injured liver, especially the cirrhotic liver. PMID- 1636900 TI - Drug therapy for inflammatory bowel disease: Part II. AB - Part II of this two-part article (See The American Journal of Surgery 1992; 164: 85-9) reviews the current definition of the role of immunosuppressive therapy in inflammatory bowel disease (IBD) and the use of antibiotics in IBD, as well as summarizes the uses of the new agents on the horizon for the treatment of IBD. Azathioprine and 6-mercaptopurine have steroid-sparing effects in patients with refractory Crohn's disease and ulcerative colitis, treat Crohn's disease associated fistulas, and are the first agents to demonstrate efficacy in the prophylaxis of Crohn's disease. Their low risk for the development of lymphoreticular malignancy remains a factor in decisions regarding their long term use. Cyclosporine is steroid sparing in active chronic Crohn's disease and, given intravenously, may help treat severe, refractory ulcerative colitis. Antibiotics have expanding roles: metronidazole is effective for the primary treatment of Crohn's disease, fistulas, abscess, bacterial overgrowth, and pouchitis (after ileoanal anastomosis). Other potential agents show promise in pilot studies but await controlled trials. PMID- 1636901 TI - Vascular lesions of the intestines. PMID- 1636902 TI - Contributions of the Zollinger-Ellison syndrome. PMID- 1636903 TI - Relative risks of complications in giant and nongiant gastric ulcers. AB - There are two divergent views regarding giant gastric ulcers. Traditionally, they have been regarded as a virulent disease prone to massive hemorrhage, intractability, and perforation. Recently, an entirely opposing viewpoint has developed that considers them no different from ordinary gastric ulcers. In this study between 1984 and 1989, 62 patients with giant ulcers (greater than or equal to 3 cm) were compared with 476 benign gastric ulcer patients to evaluate their relative risks of ulcer complications. The results showed that giant ulcers are more prone to severe hemorrhage (44% versus 27%; chi 2 test: p less than 0.009) but not more prone to free perforation. Penetration into contiguous organs occurred more frequently with giant gastric ulcers (45% versus 10%; chi 2 test: p less than 0.0001). The risk of the presence of microscopic malignancy in the macroscopically benign-looking giant ulcer is significantly greater than in the nongiant type (13% versus 3%; Fisher's exact test: p = 0.0013). The data showed that patients with giant gastric ulcers are more at risk for the development of life-threatening complications and, hence, more likely to require surgery. PMID- 1636905 TI - [Antibiotics in laryngectomized patients: prophylactic use in the postoperative period]. AB - Study of the follow-up of 43 laryngectomees during a 20 months term done at the Hospital de San Vicente de Paul, Medellin, Colombia. Twenty patients received prophylactically 1 gr of sodium cefoperazone each 12 hours for 3 doses; the other 23 were treated with penicillin/gentamycin after surgery, for 10 days. Sodium cefoperazone group showed an infection index of 16 percent compared with 65 percent of the penicillin-gentamycin group. Factors such surgical time, previous tracheotomy, cancer staging, radical neck dissection and radiotherapy were not related to the infection. Index 16 percent still is high and possible responsible causes are analyzed in the paper. PMID- 1636904 TI - Avoiding laparotomy in nonsurgical pneumoperitoneum. AB - Patients with free intraperitoneal air collections usually undergo emergency surgery, and the majority will have a gastrointestinal tract perforation. However, there is a subset of patients in whom no identifiable perforation is found at surgery. This entity of noniatrogenic, nonsurgical spontaneous pneumoperitoneum is being diagnosed more frequently at present and is commonly associated with other disease processes that, together, may suggest a benign process. Therefore, a diagnostic algorithm that would preclude operative intervention in this cohort of patients would be of paramount clinical importance. In this report, we present representative cases of the most common types of nonsurgical pneumoperitoneum, review the pathogenesis of this disorder, and discuss its relationship with pneumatosis cystoides intestinalis, pulmonary disorders, scleroderma, and gynecologic processes. Finally, we outline a diagnostic algorithm that may identify patients who can safely be observed, thereby reducing the incidence of negative laparotomies and, secondarily, the aggregate cost of health care. PMID- 1636906 TI - [Post-tonsillectomy peritonsillar abscess]. AB - Quinsy cases following tonsillectomy are very rare indeed, as proved by the scarce publications related to the subject. And all of them presented after a long term of years elapsed. From the perusal of the bibliography done by the AA. none of the cases presented close to the operation. The chance to see and treat one case starting from the fourth postoperative day compelled the AA. to report it. PMID- 1636907 TI - [Olfactory esthesioneuroblastoma (presentation of 4 cases from the authors' practice)]. AB - This is a new case of Esthesioneuroblastoma to joint the other 3 of our Archives. The opportunity is profited in order to make a revision on the subject. PMID- 1636908 TI - [Ototoxicity of deferoxamine]. AB - Deferoxamine or desferrioxamine (DFO) is a chelating agent, largely used in patients with chronic renal failure, although it has many side effects, being ototoxicity one of them. In this paper we studied the eventually adverse otologic effects of DFO in 20 patients receiving haemodialysis. A complete audiological evaluation, including pure-tone audiometry, brainstem auditory evoked potentials and high-frequency audiometry, was performed. The results showed a sensorineural hearing loss of retrocochlear origin in 3/20 cases (15%). We can accept that ototoxic effects of DFO are minimal, but no inexistent. Because of these we considered highly recommendable an accurate control of hearing in patients with renal disease receiving DFO. PMID- 1636909 TI - [Anterior reconstructive glottecomy]. AB - Shallow lesions of the glottis spreading to both sides of the middle line (T1b) have special characteristics under the viewpoint of its resection, because of the neighbourhood of the anterior commissure. Frontal and frontolateral techniques require a reconstructive step in order to avoid synechiae. The AA. report 35 cases with glottis reconstruction following several procedures: skin pedicled flap or epiglottoplasty. As the results almost the totality of the laryngectomees were "cured" after 5 years follow-up, and a high percentage of them free of tracheostomy tube. PMID- 1636911 TI - [Surgical treatment of locally advanced cancer of the tongue by total glosso pharyngo-laryngectomy]. AB - Seven patients with advanced carcinoma of the tongue (T4) were treated with total glossectomy and laryngectomy, neck dissection (radical-functional or radical traditional) and reconstruction with the pectoralis major myocutaneous flap. The AA. comment the surgical technique, the pros and the cons of the indications, the justification, the objectives and the consequences. PMID- 1636910 TI - [Olfactory esthesioneuroblastoma]. AB - The AA. present 2 cases of olfactory Neuroblastoma in different stages of histologic differentiation, which are compared. Bibliographic survey of the entity. PMID- 1636912 TI - [Laryngocele and pyolaryngocele]. AB - Report of one case of laryngocele and an other one of pyolaryngocele, in two children with laryngeal papillomatosis. Review of the treatment and the origin of the process as well. The AA. point out that with regard to the cause there is an interrelation between a congenital predisposition, represented by a large ventricular appendix, and other postnatal acquired factors, for instance, the papillomatosis present in the two patients, which justify the paper. PMID- 1636913 TI - [The reliability of proximal and distal gas samples in the capnometry of infants]. AB - To compare the accuracy of end-tidal pCO2 measurement derived from the connector (petCO2 proximal) and from the tip of the endotracheal tube (petCO2 distal), we measured paCO2, petCO2-proximal and distal in 42 infants (weight: 2500-9500 g) manually ventilated with an Ayre's t-piece breathing circuit (Kuhn modification). For distal gas sampling we used a commercially available "uncuffed tracheal tube with monitoring lumen" Mallinckrodt, Hennef, with a separate monitoring lumen leading to the distal tip of the endotracheal tube. Compared with paCO2 (26.2 +/- 5.3 mmHg), proximal gas sampling resulted in a significantly lower petCO2 (17.3 +/- 6.0; P less than 0.001) and a large arterial-end-tidal pCO2 difference (pa etCO2 9.0 +/- 6.8 mmHg). The correlation between paCO2 and petCO2 was poor (r = 0.29; n.s.). In infants weighing less than 5000 g the arterial-end-tidal pCO2 difference was found to be especially high (12.1 +/- 5.1 mmHg); it was slightly smaller in infants with more than 5000 g (5.6 +/- 7.0 mmHg). Distal petCO2 values approximated arterial pCO2 much better (petCO2 26.0 +/- 5.8 mmHg; diff pa-etCO2 0.4 +/- 3.0 mmHg, r = 0.86) even in very small children. In 12 children (weight: 2500-8000 g) ventilated with a circuit (Drager-Kreissystem) accurate petCO2 measurements were obtained from both the proximal and the distal sampling site. CONCLUSIONS: When an Ayre's t-piece is used for ventilation of children weighing less than 10 kg, distal gas sampling for petCO2 measurement should be preferred. Proximal gas sampling does not allow correct capnometry except in a circuit with one-way valves. PMID- 1636914 TI - [The incidence of hypoxia in the immediate postoperative period]. AB - Arterial oxygen saturation (SaO2) was continuously measured using a pulse oximeter in 214 spontaneously breathing adult patients in a recovery room. Hypoxaemia was defined as an SaO2 of 90% or below. The patients were divided into three groups: in group I (n = 83) monitoring was started immediately after arrival in the recovery room, just before oxygen therapy was begun. The patients in group II (n = 106) were observed during and after oxygen therapy. Patients in group III (n = 25), most of whom had regional anaesthesia, were not treated with oxygen in the recovery room. RESULTS. Clinically unexpected hypoxaemia occurred in all three groups: hypoxaemia was observed in 32.6% of patients before oxygen administration (group I). Under oxygen therapy SaO2 was normal in 99.4% of the patients; however, in 30.2% of patients hypoxaemia recurred after oxygen had been discontinued (group II). Hypoxaemic periods were seen in 24% of patients in group III. CONCLUSION. The results indicate the necessity of oxygen administration during transport and in the early postoperative period to all patients. Even during and after regional anaesthesia or brief general anaesthesia, oxygen administration appears to be indicated. Monitoring of SaO2 with a pulse oximeter has become an increasingly standard procedure in modern anaesthesia and should be mandatory. PMID- 1636915 TI - [The addition of ethyl alcohol to the irrigating fluid. Monitoring fluid absorption during transurethral resection of the prostate]. AB - The absorption of irrigation solution during transurethral prostatic resection may lead to the life-threatening condition of the so-called TUR syndrome. For a long time no early recognition procedure was easily and routinely available. This study was set up to investigate the effectiveness of ethanol as an early indicator of beginning absorption, as described by Hulten. Ethanol was therefore added to the irrigating fluid as a marker, and alcohol concentrations were measured in the exhaled breath. METHODS. For measurement of alcohol an Alcotest monitor 7110, Dragerwerk (Lubeck, FRG) was used. In preliminary experiments with 13 healthy volunteers the lowest amount of measurable i.v.-administered 2% Ringer ethanol solution was found to be about 200 ml. The irrigating fluid used was a 2% ethanol-mannitol/sorbitol solution. RESULTS. The control of breath and blood alcohol levels in 10 patients undergoing transurethral bladder surgery showed that there was no absorption of alcohol across the internal bladder lining. Of 52 patients, who had to undergo transurethral prostatic resection, 23 had positive breath alcohol values of up to 0.81/1000. In 6 patients the blood alcohol levels only were elevated (max. 0.18/1000). In 23 other patients no increased blood or breath alcohol levels were detectable. The negative breath alcohol levels in 6 patients were most probably attributable to low breath volumes due to lack of cooperation caused by pre- and/or intraoperative sedation. There were no significant changes in central venous pressure, mean arterial pressure or heart rate even at the time of maximal alcohol levels, compared with initial values. These parameters thus cannot be used for the early recognition of beginning absorption. Simultaneous monitoring of serum sodium concentrations revealed significant decreases at the time of maximal breath alcohol levels. Yet, the first indication of beginning absorption was always a positive alcohol level. Serum sodium changes followed later with increasing alcohol levels. Sodium concentration did not drop before a positive alcohol level was measured in any of these cases. CONCLUSION. It was thus proven that the addition of ethanol to the irrigating fluid and monitoring of the patient's exhaled breath with the Alco testmonitor is a simple, non-invasive system that can be routinely used for early detection of absorption during transurethral prostatic resection. Adequate adjustment of the further course of the operation was possible. The dreaded TUR syndrome did not develop in any of the patients monitored in this way. PMID- 1636916 TI - [Monitoring patients in the anesthesia recovery room. Continuous transcutaneous O2 and CO2 measurements]. AB - To establish whether continuous transcutaneous O2 and CO2 measurement in the recovery room is suitable for non-invasive monitoring of spontaneous respiration in patients newly operated upon, comparative transcutaneous and arterial pO2 and pCO2 investigations were carried out on 35 adults. There was a correlation coefficient of 0.66 between paO2 and tcpO2. The transcutaneous pO2 values measured were 45.3 mm Hg under the arterial values. When the transcutaneous CO2 values were compared with the arterial values, the correlation coefficient was 0.906. The mean transcutaneous pCO2 values measured lay around 0.7 mm Hg above the arterial values. On the basis of this slight deviation in CO2 values, the method appears to be suitable for continuous non-invasive determination of pCO2. The very large deviations in the O2 values indicate that transcutaneous measurement of oxygen partial pressure in this specific examination situation is not sufficiently reliable, which makes questionable the practice of using one piece of equipment for both measurements. In the clinical setting presented, transcutaneous O2 monitoring does not represent an alternative to close clinical observation and pulse oximetry. PMID- 1636917 TI - [Propofol versus midazolam. Long-term sedation in the intensive care unit]. AB - Sedative-analgesic treatment of patients on long-term artificial ventilation aims at protection from stress related to their disease or therapy. By stabilising both the patient's vital functions and psychological state this treatment may contribute to therapeutic success. The choice of drugs depends primarily on the nature and course of the underlying disease. Midazolam and propofol are available as hypnotics for short-term sedation during the post-operative period. The purpose of this study was to evaluate the effects of both agents on cardiovascular function, cortisol production, lipometabolism, and the recovery period following 24-h sedation. METHODS. Twenty female patients (mean body weight: 72 kg, mean age: 60 years) were randomly assigned to receive either midazolam or propofol over 24 h following major abdominal surgery. Balanced anaesthesia (halothane/O2/N2O/fentanyl) was administered for the surgical procedure. Assisted ventilation was used in all patients during the post operative sedation period. Sedation depth was maintained at III-IV on the Ramsey scale. On arrival in the intensive care unit (ICU), an initial i.v. bolus of midazolam 0.1 mg/kg or propofol 1 mg/kg was followed by a continuous infusion (midazolam: 0.1 mg/kg.h; propofol: 2 mg/kg.h). Supplementary boluses of one-half the initial dose were given if required. Post-operative analgesia was achieved with 3 mg intravenous piritramide at 2-h intervals. A 7F Swan-Ganz catheter was inserted in the pulmonary artery and haemodynamic and biochemical parameters were monitored at 4-h intervals over 24 h starting 2 h after arrival in the ICU. Catecholamines were measured by high-pressure lipid chromatography (HPLC), cortisol by radioimmunoassay, midazolam by HPLC and ultraviolet detection, and propofol by HPLC and fluorescence detection. Data were calculated as means. The statistical analysis was performed according to the Mann-Whitney test, and significance was accepted for P less than 0.05. RESULTS. On administration of the propofol bolus at the onset of sedation, a decrease in blood pressure was particularly observed in patients with masked hypovolaemia, however, this decrease was easily controlled by volume administration. Independent of the type of sedation, the haemodynamic parameters remained unchanged throughout the observation period. At all times of measurement the mean heart rate was lower in the propofol group (90/min) when compared with the midazolam group (100/min), however, this difference did not reach significance. There were also no significant differences in cardiac index at all times of measurement, although it increased in both groups within the first 12 h by 0.6 l/min.min2. In both groups this increase was associated with a reduction in peripheral resistance and an increase in rectal temperature. To achieve the desired sedation depth, midazolam was administered at a mean dosage of 0.11 mg/kg.h and propofol at 1.9 mg/kg.h. Catecholamine levels decreased in both groups within the first 8 h: after 8 h of sedation the plasma levels of noradrenaline and adrenaline were 525 and 65 pg/ml, respectively, in the midazolam group and 327 and 51 pg/ml in the propofol group. (ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1636918 TI - [Computer-assisted mechanical ventilation of newborn infants]. AB - Mechanical ventilation of mature or premature newborns is supposed to provide pulmonary gas exchange while causing minimal side effects to the respiratory system and circulation of the infants. A certain degree of alveolar ventilation, for example, can be achieved by different ventilator settings with different airway pressures (Fig. 1), and thus the corresponding effects on lung mechanics, barotrauma, and circulation differ. Parameters indicating optimal ventilator settings cannot be measured often enough in routine daily care and sometimes are difficult to interpret because of complex interactivity factors. The aim of the computer program "RespCalc" is to shorten the empirical steps of adapting respirator settings to the status of the ventilated patient by calculating the necessary data and drawing patient-specific nomograms. The computer program "RespCalc" makes use of the mathematical relationships characterizing the determinants of lung mechanics. The following data are necessary for use of the program: patient identification, weight, alveolar ventilation, recent paCO2, compliance, and resistance. By using the time-constant tau, the minimal inspiratory time as well as a maximal possible respirator rate are displayed without inducing inadvertent PEEP at a ratio of 1:1. Afterward, the planned figures of the different respirator rates and corresponding inspiration times must be typed in. The program simultaneously checks whether the previously calculated minimal figures for in- and exhalation time are maintained. If the above-mentioned figures and the typed-in ones differ, an optical and acoustical error message appears, and thus the user is forced to correct the problem.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1636919 TI - [An infected fistula following a peridural catheter]. AB - An infected fistula was observed in a woman (Age: 69 years, weight: 60 kg, height: 159 cm) 14 days after insertion and 8 days after removal of a peridural catheter inserted preoperatively for postoperative analgesia after nephrectomy (carcinoma). Due to haemodynamic problems in the early postoperative period no analgetic or local anaesthetic medication was applied via the peridural catheter. After unsuccessful antibiotic and surgical treatment the women was transferred to the Neurosurgical department five weeks after nephrectomy. Magnetic resonance imaging of the lumbar region showed a fistula (Segment L2/L3) reaching the epidural space but no epidural spreading or epidural abscess. Partial laminectomy L2/L3 was performed and the fistula excised under continuous antibiotic treatment with ofloxacin. Up until 21 months after the operation no recidivation occurred. Exact details of catheter insertion and catheter treatment in the postoperative period are not available; the fact, that no bactericide [9] local anaesthetic agents were applied, might have favoured the occurrence of this infection. Infectious complications have to be taken into consideration for the indication of peridural catheters in the perioperative period. PMID- 1636920 TI - [The emergency telephone number--the essential weak link in an emergency system. Prospective studies involving cardiac arrests observed by bystanders]. AB - The first link in the "chain of survival" concept is the activation of the emergency medical system (EMS) by a bystander after recognition of cardiac arrest (CA) or its immediate prodrome. Our ongoing study is aimed at evaluating the current effectiveness of bystander EMS activation for all cases of CA in the city and area of Mainz. Methods. Starting February 1991, we began to prospectively examine collapse-intervention intervals in all cases of CA treated by our physician-manned ambulance. Precision voice recorders carried by the ambulance crews are activated and linked to the EMS dispatcher to time the arrival of the ambulance vehicle. Time intervals starting from the time of collapse are then reconstructed from the dispatcher's time and the tapes. The emergency phone number dialled initially by the bystander and the time of collapse in witnessed cardiac arrests are identified. RESULTS. Sixty-six CAs were witnessed and included in this study. In 20% of those cases, the number dialled initially by the bystander was 19222 (EMS dispatcher), in 38% 110 (police), and in 42% other numbers (family practitioners or their on-call service, fire department). The time interval, as median (25th percentile; 75th percentile), between collapse and receipt call by the emergency dispatchers was 4 min (2; 8) for all patients (n = 66), and 6.5 min (3; 12) whenever numbers other than emergency phone numbers were dialled. All following time intervals (start of BLS or ACLS procedures) showed differences (P less than 0.05) between the 110 or 19222 group [BLS: 8.5 min (4.8; 13.1) or 10 min (7.35; 12.1); ACLS: 11.3 min (9.1; 13.45) or 12.9 min (10.6; 21.5)] vs the group, in which other phone numbers were initially dialled [BLS: 15.25 min (9.25; 19.4); ACLS: 20.11 min (12.6; 28.3)]. The first ECG rhythm showed VF in 56% and 54% in case 110 and 19222 were dialled, but only in 32% in the other group. CONCLUSION. Even one single weak link in the "chain of survival" can lower overall survival rates. An indispensable, but apparently underrated component of an effective EMS includes an informed citizenry able to call swiftly for help. Lack of an unequivocal emergency number, well known and accepted by the citizens, produces confusion and delays. In our systems, the correct medical emergency phone number (19222) was dialled in 20% of the cases only, thus demonstrating clearly the lack of public awareness of this 5-digit number. In a higher percentage, the three-digit police number (110) was dialled. In cases where numbers other than emergency numbers were dialled (42%), the longest time intervals between collapse and receipt of call by the dispatchers occurred, associated with the longest time intervals until initiation of CPR and the lowest percentage of patients found in ventricular fibrillation. We conclude that establishment of a simple three-digit EMS phone number, preferentially Europe wide, in combination with an intensification of public awareness, could be a vital step not only to reduce time intervals between collapse and CPR in our EMS system but also to improve survival. PMID- 1636921 TI - [A comparison of a tramadol/metamizole infusion with the combination tramadol infusion plus ibuprofen suppositories for postoperative pain management following hysterectomy]. AB - Postoperative pain management is still a grossly neglected field. In most cases, antipyretic analgesics alone are insufficient during the early postoperative period. Powerful narcotics are often avoided or underdosed because they are associated with the risk of respiratory depression. Some authors recommend combined infusion of tramadol and metamizole, which is assumed to provide sufficient pain relief without the risk of respiratory depression. However, this regimen has not yet been investigated in a study that meets currently accepted scientific standards. METHODS. Sixty patients who underwent vaginal hysterectomy were included in a randomised, prospective double-blind study. Thirty women received two placebo suppositories immediately after induction of anaesthesia and a postoperative infusion of tramadol and metamizole (400 mg tramadol plus 5 g [= 10 ml] metamizole in 500 ml electrolyte solution). The 30 women of the control group received two ibuprofen suppositories (585.2 mg) preoperatively and a post operative tramadol infusion (400 mg tramadol plus 10 ml placebo [NaCl 0.9%] in 500 mg electrolyte solution). The patients of both groups received 125 ml of the appropriate infusion solution as a loading dose over 10 min (corresponding to 1.25 mg metamizole and 100 mg tramadol in the metamizole/tramadol group or 100 mg tramadol in the ibuprofen/tramadol group) 10 min after awakening. The remaining solution was administered at an infusion rate of 12.5-25 ml/h (corresponding to 125-250 mg metamizole and 10-20 mg tramadol/h or 10-20 mg tramadol/h). On request or when complaining of stronger pain, the patients received an additional bolus infusion of 125 ml over 10 min. In case of insufficient pain reduction despite repeated infusion of 125-ml boli or consumption of the entire infusion solution, the patients discontinued the study and received demand-adapted intravenous titration of piritramide. Postoperative pain was evaluated on the visual analogue scale (VAS) and the 101-point numerical rating scale immediately before the start of the infusion. Pain evaluation was repeated 20, 30, 40, 60, 100, 120, and 240 min after awakening accompanied by registration of heart rate, respiratory rate, systolic and diastolic blood pressure, and side effects. RESULTS. About 60% of the entire infusion solution was administered within 60 min in both groups. Significant postoperative pain reduction in both groups and on both the 101-point scale and the VAS was observed only at 100, 120, and 240 min after awakening. In the tramadol/metamizole group, nausea occurred in 7 cases and vomiting in 1. Nine patients in this group additionally required intravenous piritramide because of insufficient pain relief. In the tramadol/ibuprofen group, 8 patients complained about nausea and 4 patients vomited. Six patients additionally received intravenous piritramide because of insufficient pain reduction. CONCLUSIONS. Satisfactory pain reduction occurred rather late despite high doses of both the tramadol/metamizole and the tramadol/ibuprofen. Both analgesic combination must be regarded as insufficient after inhalational anaesthesia because of the very slow onset of action and the high failure rate. PMID- 1636922 TI - [A fatal intraoperative cerebral ischemia following kinking of the internal carotid artery?]. AB - Postoperative neurological deficit may result from ischaemic or hypoxic hypoxaemia. Postural cerebral hypoperfusion may ensue when a pre-existing asymptomatic vascular anomaly in combination with rotation of the head for surgical positioning compromises cerebral blood flow. CASE REPORT. A 30-year-old man was referred for recraniotomy for glioblastoma. Following uneventful induction of anaesthesia, increased diuresis and progressive hypothermia were observed. The postoperative period was complicated by a seizure, followed by apnoea requiring reintubation of the trachea. A CAT scan revealed global cerebral oedema with subtotal compression of the third ventricle. Intracranial pressure was 60 mm Hg as measured by an epidural probe. On the 1st postoperative day clinical and electroneurophysical signs of brain death were observed; the patient underwent organ explantation the next day. PATHOLOGY. Pathological examination revealed pronounced global hypoxaemic lesions and an S-shaped internal carotid artery with intimal proliferation (Fig. 1). The diagnostic conclusion was cerebral ischaemia following carotid occlusion caused by carotid kinking and completed by surgical positioning (rotation of the head). CONCLUSION. Carotid kinking is a rare abnormality, and patients at risk may not be identified preoperatively. Though it is questionable whether this disaster could have been prevented at all, electroneurophysiological monitoring would have been the only early monitoring system capable of detecting diminishing cerebral blood flow. Although a request for routine intraoperative neurophysiological monitoring seems unrealistic at present, it has to be acknowledged that only such monitoring could have provided the information needed to save this patient. PMID- 1636923 TI - [Comments on the article by J. Schuttler et al. Optimized dosage strategies for total intravenous anesthesia with propofol and ketamine]. PMID- 1636924 TI - [Comments on the article by B.W. Bottiger et al. Non-surgical removal of a knotted Swan-Ganz catheter]. PMID- 1636925 TI - [The results in chronic ischemia of the lower limbs. The Granada-90 Geriatric Angiology Study (2)]. AB - Results of a study about the chronic ischaemia of the lower limbs and its correlation with age, sex and previous diagnosis, are presented. Also, a comparison between previous diagnosis and results following the methodology exposed, was made. Study group included 433 older patients, randomizadely selected and permanent residents of some geriatric centers of the Oriental Andalucy. PMID- 1636926 TI - [Embolism of the humeral artery originating in a thrombosed axillo-femoral bypass]. AB - A case of a patient, with acute arterial ischemia at the upper limb is reported. On this case, ischemia was caused by humeral arterial embolism. The embolic origin was focused on the proximal end of a thrombosed axillofemoral bypass. After a rude manipulation during surgical procedure, part of the thrombus, following the sanguineous current, occluded the humeral artery. Patient underwent an emergent surgery. Posterior course was good. Histology showed a re epithelialized, ancient thrombus. Cardiologic studies and angiography showed no others embolic focuses. PMID- 1636927 TI - [A spontaneous pseudoaneurysm of the superficial femoral artery. Apropos a case]. AB - A case of pseudoaneurysm of the superficial femoral artery is reported. No relation with traumatisms, septic, agents or others could be proved. Literature was reviewed, looking for the different etiologies of pseudoaneurysms. The extremely rare incidence of the case reported is noted. PMID- 1636928 TI - [The clinical and socioeconomic aspects of cerebrovascular diseases in Europe (a study in Turin on patients during 12 years of hospitalization)]. AB - During the period 1976-1987, 295,718 patients affected by vascular diseases have been admitted into all the public and private hospitals of Piemonte (Italy): 172,483 patients were affected by arteriopathies. 95,231 (55.2%) have been admitted because of cerebrovascular diseases: 73,511 (42.6%) were affected by diffuse form (T), 18,258 (26.5%) by TIA and 3,462 (2%) by precerebral stenosis and occlusions. (TSA). These data have been compared to the incidence of cerebrovascular disease in Europe and risk factors, sex, age, department of hospitalizations, kind of therapy and results have been investigated. In Piemonte cerebrovascular diseases show not only the highest incidence among all the vascular diseases, but they seem to be the highest cause of morbidity among all the patients admitted into the hospitals. PMID- 1636929 TI - [The seeding of porcine endothelial cells on a polytetrafluoroethylene (PTFE) substrate. An experimental study]. AB - The endotely of the vascular wall represents a natural antithrombogenic layer in intimal contact with the bloody flow. The waited success of the artificial prosthesis as replacers of minor vessels was not reached. Basically, its poor results were caused by the lake of endothelialization on the prothesical material. A cellular lap on the prosthesis, previously to the implant, could be a good resolution to this problem. If we studied the possibility to obtain a stable, endothelial monolayer "in vitro" before to the "in vivo" implant of the vascular prosthesis. We studied the role of fibronectin as a mediator between the substract and the endothelial cell. Changes on fibronectin when it is added on the culture medium were also analyzed. Although fibronectin has some positive effects as a biologic "glue" previously to the implant to the prosthesis, our results show that after the implant, fibronectin could cause a toxic effect on the adherence and survival of the endothelial cells. PMID- 1636930 TI - Blood culture: comparison of outcomes between switch-needle and no-switch techniques. AB - BACKGROUND: Because blood culture is a common test at our institution, we hoped to save money and reduce the risk of needlestick injury by modifying our current technique for the preparation of culture specimens without increasing the risk of contamination. METHODS: OBJECTIVE: To compare the contamination rates of blood culture specimens obtained by the conventional method of switching to another sterile needle before inoculation with those of specimens obtained by a method without switching. DESIGN: Cross-over study. SETTING: Department of Medicine of university hospital. PARTICIPANTS: Nursing personnel working in seven acute care medical wards in Siriraj Hospital, Bangkok, Thailand. INTERVENTIONS: From March to June 1991, participating nurses prepared blood culture specimens by means of both switch-needle and no-switch techniques in a cross-over study. All blood culture specimens were submitted to microbiology laboratory to determine the growth of microorganisms. MEASUREMENT: Growth in a culture was considered to be "true positive" or "contamination" by predetermined criteria. RESULTS: Total number of blood culture specimens was 1619; of these, 813 were prepared by switch needle technique and 806 were prepared by no-switch technique. The contamination rates were 7.6% and 8.3% for switch-needle and no-switch techniques, respectively (p = 0.61). CONCLUSIONS: The switch-needle technique may not be necessary for obtaining blood culture specimens unless the needle is obviously contaminated. The no-switch technique for the preparation of blood culture specimens is more convenient and less expensive; it also poses less risk of needlestick injury. PMID- 1636931 TI - Potential for local and systemic bacterial infection in some occupational groups in Benin City, Nigeria. AB - BACKGROUND: Many Third World countries may not have adequate facilities for rapid sensitivity testing of antibiotics as an aid to diagnosis and chemotherapy. It may therefore be valuable to relate bacterial carriage on the skin to type of work a person does. METHODS: Given areas of skin in workers from 10 occupational groups were sampled. The bacteria obtained were analyzed after growth on appropriate media. The sensitivity profiles of potential pathogens isolated from these groups, as well as of those (Staphylococcus aureus only) isolated from patients with certified infections, were carried out and the results were analyzed. RESULTS: Staphylococcus aureus constituted the most widely and frequently isolated potential pathogen. Proteus mirabilis, Escherichia coli, and Klebsiella species were also frequent colonizers of skin. There was a statistical relationship between work type and overall prevalence of bacteria on skin (p less than 0.01). Most isolates of the work groups were highly sensitive to gentamicin and cefuroxine but not to penicillin G, ampicillin, and trimethoprim plus sulfamethoxazole; isolates from infected persons were generally more resistant than were the community-acquired ones. CONCLUSIONS: A relationship may exist between the types of bacteria carried on the skin and the type of work in which a person is engaged. PMID- 1636932 TI - Position paper: immunizations. The Association for Practitioners in Infection Control, Inc. PMID- 1636933 TI - Needlestick injury: blood, mononuclear cells, and acquired immunodeficiency syndrome. AB - INTRODUCTION: Because transmission of HIV to health care workers after needlestick injury has occurred mainly a result of deep insertion of large gauge needles, blood and viable mononuclear cells transferred after needlestick injury were measured. METHODS: Needles of 20 to 27 gauge were filled with HIV-1 seropositive blood and inserted through extracorporeal human skin or parafilm covering physiologic saline solution modified Drabkin's solution, or culture medium, or inserted directly into one of these fluids, to a depth of one third of the needle length (0.5 inch) for 1 second. Volume of blood transferred was measured by both modified Drabkin's method and by chromium 51 labeling of red blood cells. Transfer of viable mononuclear cells was measured by growth in culture medium containing autologous feeder cells. RESULTS: The volume of blood transferred from a needle passed through skin varied from 312 +/- 69 nl from a 20 gauge needle to 14 +/- 4 nl from a 27-gauge needle, as measured by modified Drabkin's technique, and from 404 +/- 80 nl to 12 +/- 3.1 nl, as measured by chromium 51 labeling of red blood cells. The volume of blood transferred from a needle passed through parafilm was twice that transferred through skin. The volume of blood transferred through skin was 40% that transferred directly into fluid not covered by any barrier; blood transferred through parafilm was 80% of that transferred directly. When needles containing blood were inserted into culture medium for 1 second in the absence of a barrier, at least one viable mononuclear cell was almost always transferred to fluid from all gauges of needle tested. Insertion of needles through skin prevented transfer of all viable mononuclear cells from only 3% to 5% of 20- to 23-gauge needles, and from 12% to 32% of 26- and 27-gauge needles. Parafilm was an even less effective barrier than skin. Insertion of needles through parafilm completely prevented transfer of viable mononuclear cells from no 20- to 23-gauge needles and from only 5% to 10% of 26- and 27-gauge needles. CONCLUSION: The volume of blood transferred after needle insertion through skin for 1 second varied with the gauge of the needle and was 30-fold higher from a 20-gauge than from a 27-gauge needle. Variable mononuclear cells were transmitted after insertion through skin from more than 95% of 20- to 23-gauge needles and from 68% to 88% of 26- and 27-gauge needles. Parafilm was less effective than skin in reducing transmission of blood and viable mononuclear cells. PMID- 1636934 TI - The efficacy of mupirocin ointment and chlorhexidine body scrubs in the eradication of nasal carriage of Staphylococcus aureus among patients undergoing long-term hemodialysis. AB - BACKGROUND: Patients undergoing long-term hemodialysis have a high prevalence of Staphylococcus aureus nasal carriage, which may lead to serious infections. Mupirocin ointment has been used intranasally to eradicate S. aureus carriage in health human volunteers and health care workers. Chlorhexidine, an antiseptic with excellent antistaphylococcal activity, is widely used for handwashing and skin cleansing. METHODS: Anterior nares cultures were obtained from patients older than 18 years who were undergoing long-term hemodialysis. Patients with S. aureus nasal carriage were enrolled in the study. Axillae and groins were cultured. Patients were given mupirocin ointment intranasally twice per day for 7 days and chlorhexidine body scrubs daily for the first 3 days. Follow-up cultures were obtained from anterior nares, axillae, and groins at 1 day, and 1, 4, 8 and 12 weeks after treatment. RESULTS: One day after completion of treatment nasal carriage was eradicated in 83% of patients (15/18). After 12 weeks, 69% of patients (11/16) were free of nasal carriage. CONCLUSIONS: Success rates of eradication were excellent compared with those in other published reports. This simple and effective regimen had no major side effects. PMID- 1636935 TI - Streptococcus pyogenes outbreak in a long-term care facility. AB - BACKGROUND: Although outbreaks involving Streptococcus pyogenes have been uncommon among the elderly population, recent reports suggest that this organism is an important nosocomial pathogen among institutionalized older patients and carries significant morbidity and mortality. An outbreak of S. pyogenes, type M12, T12, occurred in a large long-term care institution serving the ill and chronically disabled. The outbreak involved 14 residents of the intermediate care facility and lasted for 4 months. METHODS: A prospective epidemiologic investigation was initiated at the onset of the outbreak. Pertinent clinical and demographic information regarding both residents and personnel was obtained by interview, review of medical and surveillance records, and examination of patients for lesions. Cultures were obtained within 24 hours of symptom onset from those with characteristic clinical symptoms. Unpaired convalescent sera were tested for group A streptococcal extracellular antigens by a rapid hemagglutination slide test. Control measures included active surveillance of residents and staff for suspicious clinical syndromes, transfer of high-risk patients, elimination of a common seating area, and improved handwashing and hygiene measures. RESULTS: The attack rate was 7.5%, with 64.3% of these patients residing on one unit. S. pyogenes was isolated from eight residents, 5 residents had a characteristic syndrome and an elevated streptozyme hemagglutination titer of 400, and 1 resident died within hours of having cellulitis of the groin. Clinical syndromes included cellulitis, pharyngitis, bronchitis, pneumonia, and septicemia. Seven residents required acute care; two residents died within 3 weeks of the onset, yielding a case fatality rate of 14.3%. CONCLUSIONS: The major means of transmission appeared to be direct contact between residents, although transmission from an infected staff member may have accounted for some cases. The hypothesis of long-term colonization was supported by the extended times between infections. The severity of illness and the apparent transmission through direct contact between residents warrants (1) early detection of infected lesions, (2) recognition of invasive illness, (3) prompt effective treatment, and (4) surveillance for S. pyogenes infections among residents and personnel. PMID- 1636936 TI - Surveillance of nosocomial infection in private psychiatric hospitals: an exploratory study. AB - BACKGROUND: The vast majority of work published about infection control programs, procedures, and practices addresses general acute care facilities. Consequently, infection-control coordinators at psychiatric hospitals have few established norms or models to use in adapting available standards to the unique needs of psychiatric hospitals and their patients. This descriptive study explored practices for the surveillance of nosocomial infections in private psychiatric hospitals. METHODS: A survey was mailed to the infection control coordinator of the 284 hospitals belonging to the National Association of Private Psychiatric Hospitals. Questionnaire data were collected anonymously. Surveys were returned by 103 (36%) of the hospitals. RESULTS: The most frequent criteria used to define the presence of nosocomial infections were the Center for Disease Control guidelines and clinical judgment, used by 38% and 39% of the respondents, respectively. Most (64%) of the respondents indicated that they did calculate a nosocomial infection rate. The most frequent method used to calculate infection rates was based on patient discharges. Sixty-five hospitals (63%) reported their most recent yearly infection rate, which ranged from 0.00 to 0.35, with a median rate of 0.05 (mean, 0.06; SD, 0.07). CONCLUSIONS: Overall, the findings reflected much variability in respondents' practices in defining nosocomial infections and calculating infection rates. We therefore suggest that both the method used to calculate the rate and facilities' definitions of nosocomial infection be considered when comparing infection rates across facilities. PMID- 1636937 TI - Tuberculosis in patients infected with human immunodeficiency virus: a problem solving approach. PMID- 1636938 TI - A universal precautions monitoring system adaptable to any health care department. AB - The Occupational Safety and Health Administration has proposed monitoring employee compliance with universal precautions, as recommended by the Centers for Disease Control. Our respiratory care department, following a four-step system development plan, has developed and implemented a universal precautions monitoring system that is easy to adapt to any health care department. The results from monitoring can be used for educational planning, quality assurance purposes, and employee performance reviews. PMID- 1636940 TI - [A preliminary evaluation of the PACS project]. PMID- 1636939 TI - U.K. experience with indwelling urethral catheters. PMID- 1636941 TI - [The laboratory in basic pediatrics]. AB - We realize a review of laboratory in Basic Pediatry, this is a method of etiological and pathogenical diagnosis, and also is good for the following and evolution in the treatment of the patient. We talk of the results in three levels: hematological, biochemical and microbiological, and in contrast with the needs of every pediatrics age. PMID- 1636942 TI - [Marginalization and health. Introduction]. PMID- 1636943 TI - [The types, causes and consequence of marginalization in Latin America]. PMID- 1636944 TI - [The causes, effects and consequences of marginalization]. PMID- 1636945 TI - [Marginality, ethnic groups and health]. AB - Main marginated ethnic groups in Span are to be found among gypsies and 3rd world immigrants. The first group include about 250,000 persons and the second group more tan half a million people. Their origins and their being past of the less fortunate social layers made them a group of health risk. Pediatric pathologies are those favored by socio-economic shortcomings as well as hygienic-sanitary deficiencies. Imported pediatric pathologies have a small incident. PMID- 1636947 TI - [Marginalization and AIDS in pediatrics]. AB - This study realizes a view of the patient, his disease and his environment, divided in newborn, kindergarten and schoolers, and into other group, adolescents. The themes are neurology clinic, familiar, social and economic environment, problems of the chronic disease, scholarships, hospitalization ahd assistance, adoption and legal rules in relation with the pediatrics patients with AIDS or positives antibodies. PMID- 1636946 TI - [Morbidity, physical growth and psychopathology in marginal populations in suburban areas]. AB - A comparative study between two distinctive groups of children documenting morbidity, physical growth and psychopathology was completed. 186 children belonging to a marginal and deprived suburban community from Valencia was defined as a experimental group (EG). 100 randomly selected children attending the emergency room of La Fe Children's Hospital was defined as control group (CG). Significant statistical differences were found between the two groups in: type and quality of prenatal care, vaccinations, low stature, depressive symptomatology and bizarre personality and behaviour. No significant statistical differences were found between the two groups in: breast feeding patterns, incidence of respiratory and gastrointestinal illnesses, weight, prematurity, low birth weight, caries and anxiety. PMID- 1636948 TI - [New antiviral agents]. PMID- 1636949 TI - [Advances in antimicrobial therapy]. AB - The recent developments in the field of antimicrobials are discussed. Amongst those discussed are the new beta lactamase inhibitors the third generation cephalosporins, the carbapenems, the quinolones, and the new macrolides. PMID- 1636950 TI - [The prevalent pathology in the low-birth-weight newborn infant]. PMID- 1636951 TI - [Hypoxic-ischemic encephalopathy in the newborn infant]. PMID- 1636952 TI - [Growth: the problems]. PMID- 1636953 TI - [Accidents in childhood and adolescence. Their magnitude and prevention]. PMID- 1636954 TI - [The frequency, causes and mortality due to accidents in Latin America]. AB - Children's accidents, or injuries, is a relevant health problem in Latin America (L.A.). There are big differences among the rates of mortality of different countries for each age group. Mortality caused by motor vehicles is outstanding but not always related to mortality by all the causes of accident. In a high number of L.A. countries rates of death by accidents from O to 14 years are higher than in U. S. A. The strategies and resources oriented to prevention have not relationship with their importance as cause of morbidity, mortality and disabling. Actions must be epidemiologically based in morbi-mortality for each country by causes, regions and the socio-economical status of the population. PMID- 1636955 TI - [Mortality due to accidents in pediatrics. Their causes and frequency]. AB - The aim of the study was to ascertain the magnitude, causes and frequency of fatal accidents in Spain in children aged O to 14 years. The information was provided by the Instituto Nacional de Estadistica. The latest data published for the five years 1982 to 1986 inclusive are studied and the causes of death by accident evaluated. PMID- 1636956 TI - [The toxic accident in childhood]. PMID- 1636957 TI - [Preventive measures in accidents in childhood]. PMID- 1636958 TI - [New findings and the potential use of the growth hormone]. AB - Use and potential use of human growth hormone (GH). The benefit of GH in classical growth hormone deficiency is well known. For the past six years, the availability of biosynthetic human growth hormone has permitted the investigation of the effect of GH in a variety of growth disorders. GH has been shown to be helpful in children with idiopathic short stature, Turner's syndrome, neuroendocrine deficiency, and chronic renal insufficiency. Although the experience is limited, GH would appear helpful in short children with intrauterine growth retardation and Noonan's and Prader-Willi syndromes. GH increases muscle mass and strength and decreases fat mass in young adults with GHD and treatment is under consideration. One of the areas of present interest and potentially of great benefit is the use of growth hormone in catabolic conditions (burns, surgical operations, patients with a prolonged stay in intensive care units, malnourished patients and patients with chronic obstructive pulmonary disease). In catabolic conditions, GH is effective in decreasing nitrogen loss, in maintaining nitrogen balance, even with hypocaloric diets, and in increasing protein synthesis and skeletal muscle mass when combined with adequate nutrition. GH has proven helpful in inducing ovulation and improving fertility in patients with GHD and in patients with ovarian resistance to gonadotropins. The field of growth hormone therapy is expanding and potentially GH could be of benefit to many children and adults with a variety of disorders. PMID- 1636959 TI - [Growth hormone-releasing factor (GRF) in the treatment of the child with a growth hormone (GH) deficiency]. PMID- 1636960 TI - [Neurosecretory dysfunction]. PMID- 1636961 TI - [The effect of the growth hormone on low familial and constitutional body heights]. PMID- 1636962 TI - [Other indications for growth hormone treatment: chronic kidney failure and Turner's syndrome]. AB - Recently, it has been demonstrated that treatment with growth hormone (GH) can accelerate height velocity in children with chronic renal insufficiency (CRI), after kidney transplantation and in Turner syndrome. The pathogenesis of growth retardation in CRI is complex. Possibly the most important factor involved is the presence of peripheral resistance to insulin-like growth factors. The administration of GH in high doses may restore catch-up growth, both in children with CRI and in kidney post-transplant patients. After 12 months of treatment height velocity increased from 4.3 to 6.6 cm/year in 4 children with CRI, and from 2.5 to 7.4 cm/year in 3 patients with kidney transplant. GH therapy alone, but even more in combination with oxandrolone increases the growth rate in Turner syndrome and may increase the final height, but the long-term results of this treatment are awaited. No undesirable collateral effects have been reported. PMID- 1636963 TI - [Vaccinations]. PMID- 1636964 TI - [New viruses in perinatology (HBV and HIV). Can we prevent their vertical transmission?]. PMID- 1636965 TI - New developments in vaccinology. PMID- 1636967 TI - [The vaccinal calendar in Latin America]. PMID- 1636966 TI - [Adverse reactions to vaccines]. AB - The adverse reactions to vaccines are still a questioned subject because of the diversity of criteria they have been assessed with. We review the different etiopathogenic mechanisms that may be involved in their production, so as their local and general clinical features. We finally suggest that in despite of presentation of the adverse reactions that can be really attributed to vaccines, in order to known their real incidence it is necessary to develop a control system all over the vaccinated population. PMID- 1636968 TI - [Vaccinations in Latin America. "The incidence and costs of avoidable diseases"]. PMID- 1636969 TI - [The schedule of systematic vaccinations in Catalonia]. PMID- 1636970 TI - [Acute bronchopulmonary infections. Introduction]. PMID- 1636971 TI - [Pneumonia in children in Latin America: morbidity, predisposing causes, mortality and costs]. AB - The paper refers to pneumonia in children under five years of age in Latin America, and covers the following toplos: morbidity, predisposing and risk factors, mortality and costs. It emphasizes the magnitude, tendency and advances in the control of the problem. High pneumonia morbidity and mortality rates are observed, with slow tendency to decrease in the majority of the countries of the Region, with some exceptions. The paper points out the importance of the National Programs of Control of Acute Respiratory Infections (ARI), specifically of pneumonia, following the guide lines of the PAHO/WHO. Special mention is made of the diagnosis, ambulatory standardized treatment and cost-effectiveness under the strategy of the Primary Health Care. The preventive measures are important, including the health education of parents and the training of the community health workers. The principal goal is to obtain a decrease of one third in the mortality of pneumonia in children, within the present. PMID- 1636972 TI - [The epidemiology, predisposing causes and costs for Spain]. PMID- 1636973 TI - [Tissue damage and immunological responses in acute bronchopulmonary infections]. AB - The appearance of a clinical infectious disease in the lung is determined by the success or failure of pulmonary defense mechanisms. This review highlights several components of the normal respiratory host defenses: the mechanical barriers, the immunoglobulins IgG and IgA, and the interaction of the alveolar macrophages and lymphocytes. For optimal clearance, not only must effectors cells, responder cells, and mediators be present, but their action must be integrated. PMID- 1636974 TI - [The etiological treatment of acute infections of the lower respiratory tract: bronchitis and pneumonias]. PMID- 1636975 TI - [An epidemiological study of allergic pathology in the general pediatric population. Mortality and costs]. PMID- 1636976 TI - [The etiopathogenetic bases for the prevention of allergic diseases]. PMID- 1636977 TI - [Prevention in food allergy]. PMID- 1636978 TI - [Prevention in respiratory allergic pathology]. PMID- 1636979 TI - [The child and his ecosystem. Introduction]. PMID- 1636980 TI - [The family and the child]. PMID- 1636981 TI - [The influence of school]. PMID- 1636982 TI - [Leisure in childhood]. PMID- 1636983 TI - [The influence of the communications media]. AB - Media is very important in promoting health education. Television is the most important as children spend great part of their time in front of it. This time consuming might compromise the development of children as they would be unable for other essential activities during TV watching. PMID- 1636984 TI - [Nutrition in the sick child. Introduction]. PMID- 1636985 TI - [The nutritional status of children with a chronic disease]. PMID- 1636986 TI - [The indicators of nutritional status]. PMID- 1636987 TI - [The nutrition of the child in a critical state]. PMID- 1636988 TI - [Enteral nutrition]. PMID- 1636989 TI - [Gastroesophageal reflux. Introduction]. PMID- 1636990 TI - [The etiopathogenesis of gastroesophageal reflux]. PMID- 1636991 TI - [Advances in the diagnosis of gastroesophageal reflux]. PMID- 1636992 TI - [Medical treatment]. PMID- 1636993 TI - [The surgical treatment of gastroesophageal reflux (GER)]. AB - From 1960 to 1990, a total of 2,476 instances of cardio-hiatal abnormalities were treated. The cause of the abnormality was achalasia (cardio-esophageal dilatation) in 2.244 instances, sliding hernias in 167 and hiatal hernias in 65. Only 213 patients underwent operations, 8,%. Gastroesophageal reflux in children has characteristics different from those of gastroesophageal reflux in adults. Knowledge of the forces that influence the closing mechanisms of the lower esophageal sphincter (LES) is the cornerstone for rational and logical intervention. The philosophy in pediatrics is that a child is a being in evolution and that the anomaly in children originates from a displaced healthy LES that has not had the opportunity to demonstrate its function because it is not in its proper place. An operation that helps to provide essential anatomic conditions immediately leads the LES to normal physiology. The A.A. discussed and presented in which cases the surgical procedure has to be taken. PMID- 1636994 TI - [The ethics code project in pediatrics. Introduction]. PMID- 1636995 TI - [The ethical aspects in pediatric therapeutics]. PMID- 1636996 TI - [Noninvasive research]. PMID- 1636997 TI - [The ethical problems in neonatology]. PMID- 1636998 TI - [The future of viral pathology]. PMID- 1637000 TI - [Basic ideas on a pediatric ethics code]. PMID- 1636999 TI - [The formulation of an ethics code in pediatrics]. PMID- 1637001 TI - [The hospital discharge project. A multicenter study for the computerization of the hospital discharge report and for the definition of the basic minimum collection of data on pediatric hospitalization]. PMID- 1637002 TI - [Informtoxic. A multimedia toxicological database]. PMID- 1637003 TI - [Target. Integrated auxological calculation]. PMID- 1637004 TI - [Computer-assisted medical teaching: the simulation of clinical cases in neonatal pathology]. PMID- 1637005 TI - [Informatics and the teaching of medicine]. PMID- 1637006 TI - [Brasilia: a city for children]. PMID- 1637007 TI - [Emotional factors and their effect on growth and immunology]. PMID- 1637008 TI - [The prevention of chronic kidney failure]. PMID- 1637009 TI - [Low weight at birth in children born at term and their final height]. PMID- 1637010 TI - [Diet, cholesterol and the late consequences]. PMID- 1637011 TI - [The sociopolitical-economic implications of genetic engineering]. PMID- 1637012 TI - [The promotion of maternal-child health for the next decade. Introduction]. PMID- 1637013 TI - [The causes of mortality and pathologies prevalent in infancy in Latin America]. PMID- 1637014 TI - [The causes of mortality and prevalent pathology in children in Portugal--their evolution and an analysis of the current situation]. AB - The author analyses the infant mortality rate amongst different age groups in Portugal, considering not only the regional variations but also its prenatal, neonatal, post neonatal, and children between 1-4 and 5-9 years components. The author takes in consideration other factors which enable one to attribute the principal causes of morbidity to each particular age group. PMID- 1637015 TI - [The causes of mortality and prevalent pathology in newborns in Spain]. PMID- 1637016 TI - [Prevalent pathology and the causes of mortality in the Spanish pediatric population from 0 to 14 years of age]. PMID- 1637017 TI - [The priority objectives and recommendations for the next decade in Spain]. PMID- 1637018 TI - [The priority objectives and recommendations for the next decade in Latin America]. PMID- 1637019 TI - [pediatric diagnosis today]. PMID- 1637020 TI - [New applications of echography: Doppler ultrasonography]. AB - The Doppler effect, the different types of Doppler echography its functions and the parameters to evaluate the blood flow are defined. The clinical applications of Doppler in paediatrics are analyzed which are grouped in four great chapters: 1) cerebral blood flow. 2) renal flood flow: a.-native kidney, b.-transplanted kidney. 3) hepatic blood flow: a.-native liver, b.-transplanted liver. 4) characterization of mass, tissue and structures. Exploration technique of different organs are described and findings in different clinical sectors are referred to, emphasizing normal patterns. PMID- 1637022 TI - Lyme disease associated with fibromyalgia. AB - OBJECTIVE: To describe the clinical and laboratory findings as well as results of treatment in patients with Lyme disease associated with fibromyalgia. DESIGN: Observational cohort study. The mean duration of observation was 2.5 years (range, 1 to 4 years). SETTING: Diagnostic Lyme disease clinic in a university hospital. PATIENTS: Of 287 patients seen with Lyme disease during a 3.5-year period, 22 (8%) had fibromyalgia associated with this illness, and 15 (5%) participated in the observational study. MEASUREMENTS: Symptoms and signs of fibromyalgia, immunodiagnostic tests for Lyme disease, and tests of neurologic function. RESULTS: Of the 15 patients, 9 developed widespread musculoskeletal pain, tender points, dysesthesias, memory difficulties, and debilitating fatigue a mean duration of 1.7 months after early Lyme disease; the remaining six patients developed those symptoms during the course of Lyme arthritis. At the time of our evaluation, late in the course of their illness, 11 patients had positive immunoglobulin (Ig) G antibody responses to Borrelia burgdorferi by enzyme-linked immunosorbent assay (ELISA), one had a positive Western blot, and the three seronegative patients had positive cellular immune responses to borrelial antigens. Four patients had abnormal cerebrospinal fluid analyses that showed an elevated protein level, a slight pleocytosis, or intrathecal antibody production to the spirochete. The signs of Lyme disease resolved with antibiotic therapy, usually intravenous ceftriaxone, 2 g/d for 2 to 4 weeks, except in one patient with persistent knee swelling. However, 14 of the 15 patients continued to have symptoms of fibromyalgia. Currently, only one patient is completely asymptomatic. CONCLUSIONS: Lyme disease may trigger fibromyalgia, but antibiotics do not seem to be effective in the treatment of the fibromyalgia. PMID- 1637021 TI - Comparison of cefuroxime axetil and doxycycline in the treatment of early Lyme disease. AB - OBJECTIVE: To compare the efficacy of cefuroxime axetil and doxycycline in the treatment of patients with Lyme disease associated with erythema migrans. DESIGN: Randomized, multicenter, investigator-blinded clinical trial with clinical evaluations during treatment (8 to 12 days) and at 1 to 5 days and 1, 3, 6, 9, and 12 months post-treatment. SETTING: Three university referral centers and one private practice. PATIENTS: A total of 123 patients with physician-documented erythema migrans. INTERVENTION: Patients were treated orally for 20 days with either cefuroxime axetil, 500 mg twice daily (63 patients), or doxycycline, 100 mg three times daily (60 patients). MEASUREMENTS: Resolution of erythema migrans and of signs and symptoms related to early Lyme disease as well as prevention of late Lyme disease. RESULTS: A satisfactory clinical outcome (success or improvement) was achieved in 51 of 55 (93%) evaluable patients treated with cefuroxime axetil and in 45 of 51 (88%) patients treated with doxycycline (difference, 5%, 95% Cl, -5% to 14%). The only complication at 1 month post treatment was Lyme arthritis in one patient who received doxycycline. Of the patients with satisfactory outcomes at 1 month post-treatment who were evaluable at 1 year post-treatment, a satisfactory outcome was achieved in 43 of 48 (90%) and in 35 of 38 (92%) patients treated with cefuroxime axetil and doxycycline, respectively (difference, -2%; Cl, -12% to 7%). Lyme arthritis did not develop in any patient after 1 month post-treatment, whereas peripheral neuropathy was suspected in one patient treated with cefuroxime axetil. Thirty percent of patients treated with cefuroxime axetil and 32% of those treated with doxycycline had one or more drug-related adverse events. Doxycycline was associated with more photo-sensitivity reactions (15% compared with 0%; P = 0.001) and cefuroxime axetil with more diarrhea (21% compared with 7%; P = 0.035) and Jarisch Herxheimer reactions (29% compared with 8%; P = 0.005). CONCLUSIONS: Cefuroxime axetil is well tolerated and appears to be equally as effective as doxycycline in the treating of early Lyme disease and in preventing the subsequent development of late Lyme disease. PMID- 1637023 TI - Long-term bone loss in men: effects of genetic and environmental factors. AB - OBJECTIVE: To identify environmental factors associated with bone loss in adult male twins and to determine the extent to which shared environmental characteristics affect estimates of the genetic influence on bone loss. DESIGN: A 16-year cohort study. SETTING: A midwestern university hospital. PARTICIPANTS: One hundred and eleven male veterans of World War II or the Korean conflict, born between 1916 and 1927. All were twins, with the sample comprising 48 pairs and 15 persons whose twin brothers were deceased or seriously ill. MEASUREMENTS: Bone mass and environmental characteristics (cigarette smoking, alcohol consumption, physical activity, dietary calcium intake, use of thiazide diuretics) measured at baseline and 16 years later. RESULTS: Rates of radial bone loss averaged 0.45% per year. Those who both smoked and used alcohol at levels greater than the median for the population had a rate of bone loss (10% in 16 years) twice the rate of those who were below the median level for both variables (5% bone loss, P = 0.003). Rates of bone loss were correlated within twin pairs, and these correlations were diminished 25% to 35% by adjustments for environmental influences on bone loss. However, statistically significant within-pair correlations remained (r = 0.4), which did not differ between monozygotic and dizygotic twin pairs after adjustments for smoking, alcohol use, dietary calcium intake, and exercise. CONCLUSIONS: Bone loss in men during mid-life is determined, at least in part, by environmental factors, including smoking, alcohol intake, and, possibly, physical activity. Rates of bone loss were similar within twin pairs, apparently because of a shared environment. PMID- 1637024 TI - The "retinoic acid syndrome" in acute promyelocytic leukemia. AB - OBJECTIVE: To describe a novel complication of therapy with all-trans retinoic acid in patients with acute promyelocytic leukemia. DESIGN: Case series. SETTING: Comprehensive cancer center. PATIENTS: Consecutive patients with a morphologic diagnosis of acute promyelocytic leukemia who underwent remission induction treatment with all-trans retinoic acid, 45 mg/m2 body surface area per day. MEASUREMENTS AND RESULTS: Nine of 35 patients (26%; 95% CI, 9% to 52%) with acute promyelocytic leukemia who were treated with all-trans retinoic acid developed a syndrome consisting primarily of fever and respiratory distress. Additional prominent signs and symptoms included weight gain, lower-extremity edema, pleural or pericardial effusions, and episodic hypotension. The onset of this symptom complex occurred from 2 to 21 days after starting treatment. Three deaths occurred; post-mortem examinations in two patients showed pulmonary interstitial infiltration with maturing myeloid cells. Six other patients survived, each achieving complete remission (five patients with all-trans retinoic acid only; 1 patient with chemotherapy). In six of the nine cases, the onset of the syndrome was preceded by an increase in peripheral blood leukocytes to a level of at least 20 x 10(9) cells/L. Certain therapeutic interventions, including leukapheresis, temporary cessation of therapy with all-trans retinoic acid, and cytotoxic chemotherapy in moderate doses were not useful after respiratory distress was established. However, the administration of high-dose corticosteroid therapy (dexamethasone, 10 mg IV intravenously every 12 hours for 3 or more days) early in the course of the syndrome resulted in prompt symptomatic improvement and full recovery in three of four patients. CONCLUSIONS: The use of all-trans retinoic acid to induce hematologic remission in patients with acute promyelocytic leukemia is associated in some patients with the development of a potentially lethal syndrome that is not uniformly accompanied by peripheral blood leukocytosis. Early recognition of the symptom complex of fever and dyspnea, combined with prompt corticosteroid treatment, may decrease morbidity and mortality associated with this syndrome. PMID- 1637025 TI - Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. AB - OBJECTIVE: To determine the clinical course and influence of antithrombotic therapy in patients with lupus anticoagulant or anticardiolipin antibodies, or both, after the first thromboembolic event. DESIGN: Retrospective survey of consecutive patients treated according to their physician's best judgment. SETTING: Secondary and tertiary referral practice. PATIENTS: Seventy patients (48 women [69%]) with a mean age (+/- SD) of 45.5 +/- 17.3 years. The antiphospholipid syndrome was primary in 51 patients (73%) and secondary to systemic lupus erythematosus in 14 patients (20%) and to chronic idiopathic thrombocytopenic purpura in 5 patients (7%). MEASUREMENTS: Site of initial and recurrent thrombotic events (venous or arterial), as well as kind (aspiring, heparin, or warfarin) and intensity of anticoagulation. RESULTS: Total follow-up after the first thrombotic event was 361.0 patient-years (mean [+/- SD], 5.2 +/- 5.6 years per patient). Thirty-seven patients (53%) had 54 recurrent events, with 2 patients experiencing fatal events. Arterial events were followed by arterial events, and venous events by venous events, in 49 of 54 instances (91%). Recurrence rates during "no treatment;" aspirin therapy; or low-, intermediate-, or high-intensity warfarin therapy (international normalized ratios [INRs] less than or equal to 1.9, 2.0 to 2.9, and greater than or equal to 3.0, respectively, or rabbit brain thromboplastin prothrombin time ratios of approximately less than 1.3, 1.3 to 1.5, and greater than 1.5, respectively) were 0.19, 0.32, 0.57, 0.07 (P = 0.12), and 0.00 (P less than 0.001) per patient-year. The follow-up periods for the five types of therapy were 161.2, 37.8, 11.3, 40.9, and 110.2 patient years, respectively. The highest INR coincident with thrombosis was 2.6. Five warfarin-treated patients had five significant bleeding events (0.031 per patient year). CONCLUSIONS: Recurrent thrombosis is a potentially serious problem for patients with lupus anticoagulant or anticardiolipin antibodies or both. The site of the first event (arterial or venous) tended to predict the site of subsequent events. Intermediate- to high-intensity warfarin therapy may confer better antithrombotic protection than low- to intermediate-intensity warfarin therapy or aspirin therapy. Further studies are needed to define more precisely the rethrombosis rate and optimal type, intensity, and duration of antithrombotic therapy. PMID- 1637026 TI - Increased incidence of Hodgkin disease in homosexual men with HIV infection. AB - OBJECTIVE: To evaluate the incidence of Hodgkin disease and non-Hodgkin lymphoma among homosexual men infected with human immunodeficiency virus (HIV). DESIGN: Cohort study with computer-matched identification of participants with the Northern California Cancer Center registry. Population rate comparisons were made with data from the Surveillance, Epidemiology, and End Results (SEER) cancer registry. PARTICIPANTS: The 6704 homosexual men in the San Francisco City Clinic Cohort study. MEASUREMENTS: Incidence of Hodgkin disease, non-Hodgkin lymphoma, HIV infection, and the acquired immunodeficiency syndrome (AIDS); calculation of sex and age-adjusted standardized morbidity ratios and attributable risk. RESULTS: Eight cases of Hodgkin disease and 90 cases of non-Hodgkin lymphoma were identified through computer matching among cohort members residing in the San Francisco Bay area from 1978 through 1989. Among the HIV-infected men, the age adjusted standardized morbidity ratio was 5.0 (95% CI, 2.0 to 10.3) for Hodgkin disease and 37.7 (CI, 30.3 to 46.7) for non-Hodgkin lymphoma. The excess risk attributable to HIV infection was 19.3 cases of Hodgkin disease per 100,000 person-years and 224.9 cases of non-Hodgkin lymphoma per 100,000 person-years. CONCLUSION: An excess incidence of Hodgkin disease was found in HIV-infected homosexual men. Additional well-designed epidemiologic studies are needed to determine whether Hodgkin disease should be considered an HIV-related malignancy. PMID- 1637027 TI - An outbreak of tuberculosis among hospital personnel caring for a patient with a skin ulcer. PMID- 1637028 TI - Pneumococcal disease during HIV infection. Epidemiologic, clinical, and immunologic perspectives. AB - OBJECTIVE: To characterize the epidemiology, clinical manifestations, and immunologic risk factors for infections with Streptococcus pneumoniae among persons infected with human immunodeficiency virus (HIV); and to delineate a practical approach for diagnosis, treatment, and prevention of these infections. DATA SOURCES: English-language articles from Index Medicus and their references as well as abstracts from conference proceedings that compared rates as well as clinical and microbiologic features of S. pneumoniae infections in HIV-infected patients. STUDY SELECTION: All human studies that included denominators, appropriate control groups, or sufficient clinical descriptions and animal studies with key immunologic observations were cited. DATA EXTRACTION: We compared epidemiologic and clinical responses to pneumococcal disease in HIV infected patients and control subjects and correlated clinical and experimental data on immunologic defects associated with HIV infection with those on regulation of pneumococcal infections. DATA SYNTHESIS: Among patients with HIV infection, the incidence of invasive pneumococcal disease is high, bacteremia is a common complication of pneumonia, and relapses occur frequently. However, the clinical presentation, response to therapy, and serotypes isolated are similar to those in persons without HIV infection, and mortality is similar or lower. Specific local and systemic defects in host defense, particularly humoral immunity, may contribute to the high incidence of invasive pneumococcal disease. CONCLUSIONS: Streptococcus pneumoniae is the leading cause of invasive bacterial respiratory disease in adults and children with HIV infection. Prompt diagnosis and antimicrobial therapy are associated with a favorable clinical outcome. Characterizing the specific immunologic defects associated with invasive pneumococcal disease in HIV-infected patients may facilitate development of successful, cost-effective strategies for prophylaxis. PMID- 1637029 TI - Variable mortality rates among dialysis treatment centers. AB - OBJECTIVE: To examine the variation in the risk for mortality among patients treated at renal dialysis facilities within a defined geographic area. SETTING: All free-standing and hospital-based dialysis facilities in a single southeastern state reported to the registry. DESIGN: Cohort of dialysis patients followed for 1 year by an end-stage renal disease registry. PATIENTS: Patients (n = 3612) aged 20 years and older receiving treatment at the dialysis facilities reporting to the registry during 1987. MEASUREMENTS: Demographic, comorbid, and severity of illness indicators were abstracted from patient records. Facility-specific risk estimates were derived from a Cox proportional hazards model. RESULTS: Facility specific mortality rates ranged between 2.0 and 10.5 deaths per 10,000 patient days. Mortality rates were higher among older persons; whites; those with a history of diabetic nephropathy, angina, or congestive heart failure; and patients with either nutritional or functional status impairment. Facility specific prevalence of each mortality risk factor varied widely. The unadjusted risk for death in a facility at the 75th percentile of risk was 1.3 times that of a facility at the median, whereas at the 25th percentile, it was 0.68 times as likely--a twofold range of risk. Controlling for differences in the prevalence of patient characteristics did not change the interquartile range in risks, and a facility's adjusted risk estimate showed a strong correlation with its unadjusted estimate (R2, 0.566; P less than 0.0001). CONCLUSIONS: Patient attributes associated with increased risk for mortality vary widely among dialysis facilities. Adjustment for these differences did not, however, substantially change either the degree of variation in mortality risks or the relative ranking of a facility's mortality. PMID- 1637030 TI - Retinoid therapy for acute promyelocytic leukemia: a coming of age for the differentiation therapy of malignancy. PMID- 1637031 TI - A new commission report on medical education. PMID- 1637032 TI - The chronic fatigue syndrome controversy. PMID- 1637033 TI - Yogurt for candidal vaginitis. PMID- 1637034 TI - Diagnostic workup of AIDS-associated diarrhea. PMID- 1637036 TI - AIDS in Africa. PMID- 1637035 TI - Diagnostic workup of AIDS-associated diarrhea. PMID- 1637038 TI - AIDS in Belle Glade. PMID- 1637037 TI - The ethos of doctors and corporations. PMID- 1637039 TI - Theories of neurodegeneration. PMID- 1637040 TI - Genetic causes of neuronal cell death. PMID- 1637041 TI - Ovarian steroid and neurotoxin models of brain aging in rodents. PMID- 1637042 TI - Modulation of NMDA excitotoxicity by redox reagents. PMID- 1637043 TI - beta-Methylamino-L-alanine (BMAA) and amyotrophic lateral sclerosis-parkinsonism dementia of the western Pacific. PMID- 1637044 TI - Ca2+ and cell death. PMID- 1637045 TI - The etiology of Alzheimer's disease: the pathogenesis of dementia. The role of neurotoxins. PMID- 1637046 TI - Overview of Parkinson's disease. PMID- 1637047 TI - Role of astrocytes in MPTP metabolism and toxicity. PMID- 1637048 TI - Characteristics of dopaminergic neurotoxicity produced by MPTP and methamphetamine. PMID- 1637049 TI - MPP+ redox cycling: a new mechanism involving hydride transfer. PMID- 1637050 TI - Creation of transgenic mice that overexpress monoamine oxidase-B neuronally. PMID- 1637051 TI - Cytopathologic features indicative of 5-hydroxytryptamine axon degeneration are observed in rat brain after administration of d- and l-methylenedioxyamphetamine. PMID- 1637052 TI - Biochemical basis of structural electivity of MPTP-like neurotoxicity. PMID- 1637053 TI - Indole-N-methylation of beta-carbolines: the brain's bioactivation route to toxins in Parkinson's disease? PMID- 1637054 TI - Manganese as possible ecoetiologic factor in Parkinson's disease. PMID- 1637055 TI - Similar inhibition of mitochondrial respiration by 1-methyl-4-phenyl-pyridinium (MPP+) and by a unique N-methylated beta-carboline analogue, 2,9-dimethyl norharman (2,9Me2NH). PMID- 1637056 TI - Degeneration of rat locus coeruleus neurons is not accompanied by an irreversible loss of ascending projections. Evidence for reestablishment of forebrain innervation by surviving neurons. PMID- 1637057 TI - Mitochondrial mechanisms of neurotoxicity. PMID- 1637058 TI - Effects of prolonged chronic dietary treatment with AlCl3 on selected metabolisms and memory in rats. PMID- 1637059 TI - ATP deficits and neuronal degeneration induced by 3-nitropropionic acid. PMID- 1637060 TI - MPTP-induced ATP loss in mouse brain. PMID- 1637061 TI - MK-801 prevents methamphetamine-induced striatal dopamine damage and reduces extracellular dopamine overflow. PMID- 1637062 TI - Generic inhibition of mitochondrial electron transport by MPP+ and other charge shielded lipophilic cations. PMID- 1637063 TI - Characterization of [3H]MK-801 binding in LA-N-2 neuroblastoma cells. PMID- 1637064 TI - Patterns of Fos expression suggest similar mechanisms of action for the excitotoxins domoic and kainic acid. PMID- 1637065 TI - Analysis of the protective effects of 21-aminosteroids in MPP(+)-induced neurotoxicity to dopaminergic neurons in mesencephalic cultures. PMID- 1637067 TI - L-dopa potentiates the neurotoxicity of some amphetamine analogues. PMID- 1637066 TI - Age and dietary factors in hippocampal sensitivity to trimethyltin. PMID- 1637068 TI - The platelet plasma membrane serotonin transporter catalyzes exchange between neurotoxic amphetamines and serotonin. PMID- 1637069 TI - Brain-derived neurotrophic factor protects dopaminergic cells from 6 hydroxydopamine toxicity. PMID- 1637070 TI - Evidence for a common mechanism of serotonin release induced by substituted amphetamines in vitro. PMID- 1637071 TI - In vivo and in vitro pharmacologic profile of two new irreversible MAO-B inhibitors: MDL 72,974A and fluorodeprenyl. PMID- 1637072 TI - Antioxidative therapeutic strategies for Parkinson's disease. PMID- 1637073 TI - Cholinergic toxins and Alzheimer's disease. PMID- 1637074 TI - Neurochemical responses to 6-hydroxydopamine and L-dopa therapy: implications for Parkinson's disease. PMID- 1637075 TI - Comparison of MPTP and amphetamines as dopaminergic neurotoxins. PMID- 1637077 TI - Calcitonin gene-related peptide: a neuropeptide generated as a consequence of tissue-specific, developmentally regulated alternative RNA processing events. PMID- 1637076 TI - Features of the dopaminergic neurotoxin MPTP. PMID- 1637078 TI - The calcitonin family of peptides. PMID- 1637079 TI - Calcitonin gene-related peptide in the brain, spinal cord, and some peripheral systems. PMID- 1637080 TI - Localization of calcitonin gene-related peptide in the rat and human pituitary gland using immunocytochemistry and in situ hybridization. CGRP expression during ontogeny and after endocrine manipulations. PMID- 1637081 TI - Structure-activity analysis of CGRP's neurobehavioral effects. PMID- 1637082 TI - Calcitonin gene-related peptide in the brain. Neurochemical and behavioral investigations. AB - CGRP in the amygdala is concentrated in an area close to the central nucleus. High potassium releases CGRP, and this release, as well as the tissue concentration of CGRP in the amygdala, can be influenced by neuroleptic drugs. Both molecular forms, alpha- and beta-CGRP, are present in the amygdala in a ratio of approximately 3:1. CGRP influences social behavior in chicken. Therefore, CGRP may have a prominent role in psycho-behavioral function and may be a target for action and/or side effects of antipsychotic drugs. PMID- 1637083 TI - Enteric and visceral afferent CGRP neurons. Targets of innervation and differential expression patterns. PMID- 1637084 TI - Release of calcitonin gene-related peptide from sensory neurons. AB - CGRP is released from capsaicin-sensitive sensory neurons in a Ca(2+)-dependent manner in a variety of peripheral organs as well as from central terminals. The mechanisms for CGRP release by low concentrations of capsaicin, electrical antidromic nerve stimulation, and bradykinin have several similar characteristics regarding sensitivity to TTX, CTX, and alpha 2-adrenoceptor activation. High capsaicin concentration and nicotine evoke CGRP release via other mechanisms. The effects of capsaicin, resiniferatoxin, and SO2 are blocked by RR, which probably inhibits ion fluxes associated with capsaicin receptor activation. CGRP released upon irritation of peripheral branches of primary afferents may evoke a variety of cardiovascular actions and influence motility in the gastrointestinal and urogenital tracts. PMID- 1637085 TI - Calcitonin gene-related peptide in the regulation of cardiac function. PMID- 1637086 TI - Membrane actions of calcitonin gene-related peptide in cardiac and smooth muscle myocytes. AB - Calcitonin gene-related peptide is a 37-amino acid neuropeptide acting as a transmitter of nonadrenergic, noncholinergic nerves in the heart. Binding sites of high affinity have been reported in coronary arteries, in atria, and, of minor density, in ventricular myocardium. These sites are likely linked to G-proteins mediating modifications of ion channel opening probability and duration and to stimulation of adenylate cyclase activity and cAMP-mediated alterations of ion channel activities. In isolated and perfused guinea pig hearts, low concentrations of CGRP (1-3 nM) exerted no chronotropic effect, but increased coronary flow slightly. Atrioventricular conduction duration and effective refractory period of atrioventricular conduction were prolonged by 3 nM of CGRP. The higher concentration of 10 nM increased the sinus rate, and the effects on the atrioventricular node were counterbalanced. HV and QRS duration of the ECG remained essentially unchanged, but persistent ventricular fibrillation was inducible by burst stimulation in all CGRP-treated hearts. Results in human myometrial myocytes indicate that CGRP exerted direct G protein-mediated activation of potassium channels, leading to hyperpolarization and smooth muscle relaxation. Activation of potassium channels, most prominent in smooth muscle relaxation, is likely an additional factor in the cardiostimulatory profile of CGRP. PMID- 1637087 TI - Role of calcitonin gene-related peptide in gastrointestinal blood flow. PMID- 1637088 TI - Inhibition of gastric acid secretion and ulcers by calcitonin [correction of calciton] gene-related peptide. AB - A central action of CGRP to inhibit gastric acid secretion, demonstrated in rats and dogs, is mediated at least in rats through modulation of parasympathetic outflow to the stomach. The centrally mediated protective effects of CGRP against ethanol-induced lesions is unique to this peptide and not shared by other centrally acting inhibitors of gastric function. It may be related to the increase in gastric mucosal blood flow induced by central CGRP. The presence of CGRP-like immunoreactivity and receptors in medullary nuclei receiving visceral information and influencing vagal outflow suggests a possible role of the peptide in the central regulation of gastric function. Peripheral injection of CGRP is well established to inhibit acid secretion in rats, dogs, rabbits, and humans. Its antisecretory effect is unlikely to be related to a direct action on the parietal cells. It involves specific and marked release of gastric somatostatin through an interaction with CGRP receptors characterized on D cells and coupled with cAMP. In addition, CGRP induces a decrease in acetylcholine transmission in the enteric nervous system, which may contribute to the inhibition of acid. The rich innervation of the stomach with CGRP-like immunoreactivity, which forms the major component of gastric sensory fibers, along with peptide release by sensory stimulation and potent actions on gastric secretions suggests a role of the peptide in the regulation of gastric function. PMID- 1637089 TI - The physiology of calcitonin gene-related peptide in the islet compared with that of islet amyloid polypeptide (amylin). AB - Following the discovery of a second gene containing a CGRP-like sequence, we demonstrated that "beta-CGRP" was indeed translated as a 37-amino acid peptide in vivo and was the predominant form of CGRP produced by the enteric nervous system. The presence of CGRP in the islet has been reported by several groups. We now show that beta-CGRP is again the major form. Another 37-amino acid peptide was recently isolated from islet amyloid deposits and found to have approximately 50% amino acid sequence homology with CGRP. Islet amyloid polypeptide, or amylin, is co-localized with insulin to the beta-cell secretory granule and is synthesized and released in parallel with insulin in response to a range of physiological and pharmacological stimuli. IAPP was subsequently shown, like CGRP, to inhibit the release of insulin pharmacologically. Interestingly, it was also shown to decrease the uptake of glucose by striated muscle, though it was considerably less potent than CGRP. This led to the suggestion that IAPP might be a circulating hormone regulating peripheral insulin sensitivity. Infusion of IAPP in human volunteers to produce plasma concentrations more than 100-fold higher than those seen physiologically, however, failed to alter peripheral glucose disposal. We conclude that beta-CGRP and IAPP are likely to play a role in local paracrine control of the islet. PMID- 1637090 TI - Calcitonin gene-related peptides: influence on intestinal ion transport. PMID- 1637091 TI - Calcitonin gene-related peptide in inflammatory bowel disease and experimentally induced colitis. AB - Pronounced changes in gut neuropeptide content have been observed in colonic tissues from animals with acute experimental colitis and in some patients with inflammatory bowel disease. The early decrease of CGRP in the colon during colitis in the animal studies suggest that CGRP is released during the inflammatory process. No data are available showing the biological action of released CGRP during inflammation. The sensory neurotoxin capsaicin was used in animal studies to examine the effect of sensory nerves on inflammation and healing in experimental animal models. The severity of colitis was enhanced after capsaicin pretreatment in acute and chronic animal models of colitis. These data support the hypothesis that sensory nerves exert a protective and healing promoting function in the gut. CGRP is a good candidate for this action of sensory nerves because it is a major component in sensory nerve fibers. How CGRP exerts its protective function in the intestine is unknown. Data from gastric ulcer models support the hypothesis that a main action of CGRP is regulation of mesenteric and mucosal blood flow resulting in enhanced protection and tissue healing. Other effector roles of CGRP afferent nerve endings could also be considered. PMID- 1637092 TI - Calcitonin gene-related peptide in the regulation of urinary tract motility. PMID- 1637094 TI - Molecular mechanisms of cell-specific and regulated expression of the calcitonin/alpha-CGRP and beta-CGRP genes. AB - The calcitonin/CGRP gene family utilizes several fundamental mechanisms for regulation of gene expression. The structural diversity of the family depends both on tissue-specific RNA processing and the presence of multiple, independently regulated genes. Our laboratory has been studying the structure and expression of the rat calcitonin/alpha-CGRP and beta-CGRP genes. We have studied the processing of transcripts from these genes by introducing a variety of mutated and hybrid genes into several cell lines to identify sequences critical for processing regulation. These mutant genes have ranged from point mutations to exchanges of entire splice sites, as well as chimeric constructs between the calcitonin/alpha-CGRP and beta-CGRP genes. The beta-CGRP gene provides a unique insight into the role of cis-acting sequences in tissue-specific splicing events. The rat beta-CGRP gene has an overall structure similar to that of the calcitonin/alpha-CGRP gene, but the former lacks an exon encoding a calcitonin like hormone. Although the beta-CGRP gene contains splice junction sequences analogous to those utilized for alternative splicing in the calcitonin/alpha-CGRP gene, alternatively spliced products from regions within the beta-CGRP gene are not observed. Substitution of specific domains from the calcitonin/alpha-CGRP gene into the beta-gene can reconstitute some, but not all, aspects of alternative RNA processing. The results of transfection studies suggest that multiple regions within these genes contribute to alternative RNA splicing. PMID- 1637093 TI - Calcitonin gene-related peptide and peripheral nerve regeneration. PMID- 1637095 TI - Calcitonin gene-related peptide is chemotactic for human T lymphocytes. AB - Certain neuropeptides, such as CGRP, are associated with C-type nerve fibers in the skin and are known to be proinflammatory mediators. Because of their probable role in various cutaneous diseases, we investigated the effect of alpha- and beta CGRP on human leukocyte migration in a 48-well microchemotaxis chamber using a 5 microns-pore filter. Elutriated peripheral blood leukocytes (enriched 80-90% for CD3+ and 10-20% for CD20+ lymphocytes) were added to the upper wells, and CGRP to the lower ones in a dose range of 10(-19)-10(-5) M; both were diluted in RPMI medium containing 0.05% fetal calf serum. The chamber was incubated at 37 degrees C for 2.5 hours, and the filter was washed and stained. The mean number of cells migrating through the filter was calculated for quadruplicate wells in each treatment group. Chemotactic activity was expressed as a migration index (MI = number of cells responding to CGRP/media control). Both alpha- and beta-CGRP were optimally chemotactic for leukocytes at approximately 50 pM, with a mean migration index of 11.5 for filter-adherent cells (n = 13 experiments); migration due to chemokinesis was minimal, as measured by checkerboard analysis. Almost all leukocytes that responded to CGRP were T cells (TCs), and the CD4 to CD8 ratio was similar to that of the input population; B cells were not observed. CGRP induced migration appears to be a specific receptor-mediated event, as pretreating the cells with CGRP resulted in significant down-regulation of their chemotactic response to CGRP, but not to interleukin-1 alpha. Our data suggest that the release of CGRP from free nerve endings near the dermal-epidermal junction could influence cutaneous TC trafficking. As neuropeptides exacerbate (possibly initiate) the inflammatory process, they are likely to be important pharmacological targets in dermatological disorders. PMID- 1637096 TI - Eosinophil chemotactic peptide sequences in rat alpha-CGRP. Activation of a novel trophic action by neutral endopeptidase 24.11. AB - Rat alpha- and alpha-CGRP are substrates for endopeptidase 24.11 in vitro. Cleavage of both peptides occurs at several points, including an unusual substrate recognition site to the amino side of ala36. In alpha-CGRP this resulted in the early formation of val32-gly-ser-glu35, a sequence previously reported to be a component of the eosinophil chemotactic factor of anaphylaxis (ECF-A). The biological activity of this peptide fragment was confirmed by bioassay. Chemotactic activity in other hydrolysis fragments of both alpha- and beta-CGRP was observed. Both alpha- and beta-CGRP could thus serve as precursors to different eosinophil chemotactic peptide fragments. A novel function of endopeptidase 24.11 may be to modify rather than to terminate the biological activity of CGRP peptides. PMID- 1637098 TI - Distribution of calcitonin gene-related peptide in the central nervous system of the rat by immunocytochemistry and in situ hybridization histochemistry. PMID- 1637097 TI - Evidence that calcitonin gene-related peptide contributes to inflammation in the skin and joint. AB - Calcitonin gene-related peptide produces dose-related vasodilatation after intradermal injection in several species. In the present study, CGRP increased blood flow in rabbit skin but had no direct effect on edema formation in rat or rabbit skin or in the rat knee joint. However, CGRP produced significant potentiation of edema formation when co-injected with histamine, a potent mediator of increased vascular permeability. Therefore, release of CGRP from stimulated C-fiber nerves may contribute to the vascular changes that are an integral part of the inflammatory process. The activity of the putative CGRP antagonist CGRP8-37 (300 pmol) against CGRP was also investigated in rabbit and rat skin. Whereas it was found to selectively antagonize the effects of CGRP in rabbit skin, the antagonist produced edema in rat skin at the same dose. Thus, CGRP8-37 may be used in the rabbit to study the effects of endogenously released CGRP, but caution is required when this antagonist is used in the rat. PMID- 1637099 TI - CGRP in brain stem motoneurons. Dependent on target innervated? PMID- 1637100 TI - CGRP as a marker of the climbing fibers during the development of the cerebellum in the rat. AB - Olivary fibers express CGRP-LI until the nest phase of their development and never in the next postnatal steps, that is, the "capuchon" stage. Together with other results presented in this volume regarding the postnatal development of CGRP binding sites in the cerebellar cortex, these immunohistologic findings suggest a role for CGRP in reshaping connectivity and in synapse stabilization of cerebellar circuitry during postnatal development. PMID- 1637101 TI - Immunohistochemical localization of calcitonin gene-related peptide in the rat eye. Response to capsaicin pretreatment. PMID- 1637102 TI - Calcitonin gene-related peptide is released from cholinergic synapses. PMID- 1637103 TI - Is there a synaptic innervation of pelvic neurons by CGRP-immunoreactive sensory nerves? PMID- 1637104 TI - Pharmacological effects of capsaicin treatment on innervation of the rat kidney with calcitonin gene-related peptide. PMID- 1637105 TI - CGRP-like immunoreactive nerve endings in the rat knee joint. PMID- 1637106 TI - CGRP immunoreactivity in the mammalian pancreas. PMID- 1637107 TI - Long-term increase in CGRP levels in rat spinal dorsal horn following skin ultraviolet irradiation. A mechanism of sunburn pain? PMID- 1637108 TI - Production of CGRP in three continuous cell lines from human medullary thyroid carcinomas. PMID- 1637109 TI - An assessment of the anabolic skeletal actions of the common-region peptides derived from the CGRP and calcitonin prohormones. PMID- 1637110 TI - Ibuprofen, indomethacin, and high-dose aspirin, but not low-dose aspirin or imidazole, inhibit CGRP elevations in plasma during endotoxicosis. PMID- 1637111 TI - Characteristics of CGRP-induced relaxation in rabbit ophthalmic artery. PMID- 1637112 TI - Increased sympathetic outflow to the gut by cerebral CGRP inhibits duodenal, pancreatic, small intestinal, and biliary functions. PMID- 1637113 TI - Preparation of a monoclonal antibody to rat alpha-CGRP for in vivo immunoneutralization of peptides. PMID- 1637114 TI - Stimulation of rat antral CGRP release by intraluminal peptone. PMID- 1637115 TI - Sialoadenectomy selectively increases rat gastric CGRP. Interaction with capsaicin-sensitive afferents. PMID- 1637116 TI - Multiple mechanisms in the action of alpha-CGRP in rat stomach. PMID- 1637117 TI - Calcitonin gene-related peptide mediates the gastric hyperemic response to acid back-diffusion. PMID- 1637118 TI - Antagonism of the motor effects of CGRP and of capsaicin on the guinea pig ileum by human CGRP8-37. PMID- 1637119 TI - Calcitonin gene-related peptide as modulator of cholecystokinin-induced contraction of guinea pig gall bladder strips in vitro. PMID- 1637120 TI - Effect of calcitonin gene-related peptide on passive avoidance behavior in rats. Role of transmitters. PMID- 1637121 TI - Neurochemical effects of CGRP. PMID- 1637122 TI - Inhibition of insulin-stimulated glycogen synthesis in skeletal muscle by resiniferatoxin is probably due to a mechanism involving CGRP. PMID- 1637123 TI - Identification and partial characterization of the salmon calcitonin/CGRP gene by polymerase chain reaction. AB - The polymerase chain reaction was used to amplify sequences encoding calcitonin and CGRP in the genomic DNA of salmon. Amplification products of the expected length were cloned and sequenced. In this way a new CGRP-coding sequence was identified. The new sequence and the known salmon calcitonin-coding sequence were shown to be part of one gene, implying that alternative gene expression takes place in fish. PMID- 1637124 TI - A method of surgical correction of myopia by fashioning a new optically active epithelial surface: keratoepitheliomileusis. AB - A new form of refractive keratoplasty for the correction of myopia was developed using a new approach to the problem. The midperipheral annular area of the recipient cornea was deepithelialized, and Bowman's layer was removed using a special bore coated with diamond crumbs. A cryolathed annular graft was placed on this prepared midperipheral area of the recipient cornea concentrically with its center. As a result of subsequent reepithelialization inside the transplanted ring, a regular optically active surface was formed. The refractive effect gradually appeared eight to ten weeks after surgery This new optically active surface acted as a lens, consisting of epithelial cells on top of the host cornea. The method required neither cutting of the stroma nor any manipulation in the optical zone of the cornea. A new term "keratoepitheliomileusis" was coined for this new procedure. Eleven patients (12 eyes) with high myopia ranging from 7.5 to 22.0D underwent keratoepitheliomileusis. The refractive and visual results found after four to 16 months of follow-up are presented. Emmetropic refraction occurred in three patients. In the other nine eyes, the deviation from emmetropia ranged from 0.75 to 2.5D. In all patients, uncorrected visual acuity was improved considerably (up to 0.3 to 1.OD) without loss in their best-corrected vision. PMID- 1637125 TI - Multifocal choroiditis with evidence of Lyme disease. AB - A 32-year-old man had multifocal choroiditis without vitreous involvement. The diagnosis of Lyme disease was suggested by serial enzyme-linked immunosorbent assays of his serum and a cerebrospinal fluid specimen. The ocular findings resembled those seen in patients with acute posterior multifocal placoid pigment epitheliopathy (APMPPE). The active lesions resolved after administration of a two-week course of intravenous ceftriaxone. This case suggests that some cases of APMPPE actually may be Lyme disease. PMID- 1637126 TI - Presumed exudative retinal detachment after cryotherapy in retinopathy of prematurity. AB - Cryotherapy of the peripheral avascular retina in selected cases of retinopathy of prematurity has been shown to reduce the incidence of posterior retinal detachment, retinal fold involving the macula, and retrolental tissue. Although exudative retinal detachments have been described after cryotherapy during scleral buckling procedures, to our knowledge, this observation has not been reported after cryotherapy in retinopathy of prematurity. We describe such a case. PMID- 1637127 TI - Nondetectable electroretinogram in combined methylmalonic aciduria and homocystinuria. AB - We present the case of a patient with congenital methylmalonic aciduria with homocystinuria and a nondetectable electroretinogram. To our knowledge, this is a new entity to be considered in the differential diagnosis of nondetectable electroretinography in infancy. PMID- 1637128 TI - Choroidal vascular aneurysm with massive choroidal hemorrhage. AB - A rare case of a choroidal vascular aneurysm arising from the short posterior ciliary artery is reported in a 40-year-old woman. The aneurysm was detected by fluorescein angiography. It caused recurrent choroidal hemorrhage with blindness as the outcome. The diagnosis of aneurysm would have been missed without fluorescein angiography. A search should be made for choroidal vascular aneurysm in cases of spontaneous choroidal and vitreous hemorrhage both clinically (using fluorescein angiography) and histopathologically (in the event of enucleation of the eyeball). PMID- 1637129 TI - Presenting signs and symptoms of choroidal melanoma: what do they mean? AB - Presenting signs and symptoms of 193 patients with choroidal melanomas (followed for up to 152 months) were recorded using retrospective chart review. Eighty patients (41%) had no symptoms (the melanoma was found during routine ophthalmologic examination in 65 patients and during treatment for other eye problem in 15 patients). We found 113 patients (59%) had symptoms (visual acuity or visual field defects, 77 patients; flashes or floaters, 30 patients; pain, 5 patients, and metastatic disease, 1 patient). The tumor size was related to the presence or absence of symptoms (chi-square, 10.6; P = .005). More tumors that presented with symptoms were medium sized (64%) than large (27%). Men had significantly more symptoms (chi-square, 4.1; P = .04). The right eye was more likely to be involved in patients with symptoms (chi-square, 7.3; P = .007). Kaplan-Meier survival analysis for age, sex, presence of tumor or retinal detachment in the macula, tumor location, presence of symptoms, laterality, and tumor size showed that only tumor size was related to a difference in incidence of metastasis (log-rank chi-square, 12.9; P = .002). With increased tumor height, the probability of developing metastasis was greater. PMID- 1637130 TI - Spastic entropion after cataract surgery. AB - Spastic entropion is an acute eyelid condition seen in patients with acute inflammatory ocular conditions. It has been reported after cataract surgery. We describe three cases of spastic entropion after cataract surgery that did not resolve after the ocular irritation subsided. All were associated with eyelid and/or cul-de-sac injection of antibiotics and corticosteroids or anesthetic solution. All had dehiscence of the capsulopalpebral fascia. Spastic entropion is an evolving stage toward permanent entropion. PMID- 1637131 TI - Proton magnetic resonance spectroscopic imaging for metabolic characterization of demyelinating plaques. AB - We used proton magnetic resonance (MR) spectroscopic imaging to determine the serial changes in MR signals from choline, creatine, lactate, and N acetylaspartate in and around a large demyelinating lesion followed over a period of 8 months. Elevated lactate and choline signals were observed at the first examination 3 days after the onset of symptoms. Reduced N-acetylaspartate signals were observed a few days afterward. The abnormal metabolite signals varied in different regions of the lesion and extended beyond the borders of abnormal signal intensity seen on conventional MR imaging (MRI). On the last examination at 8 months when the lesion appeared much smaller on MRI, choline signals from the center of the lesion were still high, but were falling. Choline signals outside the lesion on MRI had returned to normal as had lactate signals everywhere. Importantly, there was no recovery of N-acetylaspartate signals in or adjacent to the lesion on MRI. This serial study demonstrates the potential of MR spectroscopic imaging for characterizing the chemical pathological evolution of demyelinating lesions in ways that conventional MRI cannot. We propose that abnormal signals from choline can indicate recent regional demyelination, while persistent abnormal signals from N-acetylaspartate can provide an index of irreversible damage in the nervous system. PMID- 1637132 TI - Mild senile dementia of the Alzheimer type. 4. Evaluation of intervention. AB - The design of trials of interventions intended to slow or arrest the progression of senile dementia of the Alzheimer type must be based on analysis of the natural history of the disease. Using a random coefficients statistical model, we analyzed the natural history of senile dementia of the Alzheimer type in carefully defined subjects with mild disease (n = 68) for periods of up to 10 years. Subject performance was assessed longitudinally on batteries of clinical and psychometric measures. The characteristics of these measures were analyzed relevant to their utility as outcome measures for long-term trials in patients with senile dementia of the Alzheimer type. Estimates were made of sample sizes required to show arrest, and 50% or 25% slowing in the progression of mild disease. We suggest that a clinically relevant global measure, such as the Sum of Boxes of the Clinical Dementia Rating scale, and a performance-based clinical scale or psychometric measure would be appropriate in a 12- or 24-month trial enrolling subjects with mild senile dementia of the Alzheimer type. PMID- 1637133 TI - Localization of extratemporal epileptic foci during ictal single photon emission computed tomography. AB - We obtained single photon emission computed tomography (SPECT) scans with technetium-99M-hexamethyl-propylene-amine-oxime in 11 patients during 12 extratemporal partial seizures (9 simple partial, 3 complex partial). Ten ictal SPECT studies in 9 patients showed a focal region of hyperperfusion, which agreed with electrical seizure onset in 5 and with clinical seizure localization in 4 in whom ictal electroencephalography was not localized. Contralateral cerebellar and ipsilateral basal ganglia hyperperfusion was seen in 3 patients with a frontal lobe seizure focus. Ictal hyperperfusion was well circumscribed, unlike the diffuse hyperperfusion changes reported during temporal lobe seizures. This observation may indicate a different degree of seizure spread in temporal as opposed to extratemporal epilepsy. Because electroencephalographic localization is often elusive in extratemporal seizures, ictal SPECT may be very helpful for the localization of extratemporal foci. PMID- 1637134 TI - Multifocal inflammatory leukoencephalopathy with 5-fluorouracil and levamisole. AB - A cerebral demyelinating disease developed in 3 patients during adjuvant therapy with 5-fluorouracil and levamisole for adenocarcinoma of the colon. None of the patients had evidence of metastatic disease or prior neurological disease. The duration of chemotherapy before onset of neurological symptoms ranged from 15 to 19 weeks. The total dose of 5-fluorouracil was 9.7 to 15.7 gm. The total dose of levamisole was 2.7 to 3.75 gm. Two patients presented with a subacute (2-3 weeks) progressive decline in mental status and ataxia. The third patient had two unexplained episodes of loss of consciousness. In each, magnetic resonance imaging with gadolinium demonstrated prominent multifocal enhancing white matter lesions. Cerebral biopsy was performed stereotaxically in 2 patients. The morphological features were those of active demyelinating disease. The myelin loss was associated with numerous dispersed as well as vasocentric macrophages, sparing of axons, and perivascular lymphocytic inflammation. Electron microscopy confirmed the light microscopic findings. All 3 patients improved after cessation of chemotherapy and a short course of corticosteroid therapy. Our patients represent the first reported examples of an inflammatory leukoencephalopathy associated with the administration of 5-fluorouracil and levamisole. This syndrome may represent the pathological basis for 5-fluorouracil neurotoxicity, although we cannot completely exclude the role of levamisole. PMID- 1637135 TI - The spectrum of neurological disease in patients with systemic cancer. AB - To ascertain the range of neurological problems in patients with systemic cancer, we prospectively evaluated neurological symptoms, neurological diagnoses, and primary tumors in all patients with a history of systemic cancer examined by the Department of Neurology at the Memorial Sloan-Kettering Cancer Center, from Jul 1, 1990, to Dec 31, 1990. Of the 815 patients seen for neurological symptoms, less than half (45.2%) had metastatic involvement of the nervous system. The three most common symptoms were back pain (18.2%), altered mental status (17.1%), and headache (15.4%). The most common neurological diagnosis was brain metastasis (15.9%), followed by metabolic encephalopathy (10.2%), pain associated with bone metastases only (9.9%), and epidural extension or metastasis of tumor (8.4%). Of 133 patients with undiagnosed back or neck pain, 44 (33%) had epidural extension or metastases from tumor and 40 (30%) had pain associated with vertebral metastases only. In 15 (11%) the cause for the back pain was unrelated to metastatic disease. Of 132 patients seen on initial consultation for altered mental status, metabolic encephalopathy was the major neurological diagnosis (80; 61%); 20 (15%) had intracranial metastases. Of 97 patients with undiagnosed headache, 59 (61%) had a nonstructural cause. Fifty-three of these patients had either migraine, tension headache, or headache related to systemic illness (e.g., fever, sepsis). These results indicate that even in patients with systemic cancer, a group particularly prone to developing neurological disease that can be diagnosed radiologically, the role of clinicians remains important in helping distinguish noncancer-related and nonmetastatic neurological problems. PMID- 1637136 TI - Selective accumulation of aluminum and iron in the neurofibrillary tangles of Alzheimer's disease: a laser microprobe (LAMMA) study. AB - We report the results of an examination of the elemental content of neurofibrillary tangle-bearing and neurofibrillary tangle-free neurons identified within the hippocampus of 10 subjects with Alzheimer's disease and 4 neuropathologically intact age-matched control subjects. The study employed laser microprobe mass analysis (LAMMA), a technique that provides extremely sensitive multielement detection in plastic-embedded, semithin-sectioned tissues. Evidence for the selective accumulation of aluminum within the neurofibrillary tangle bearing neurons was obtained in all 10 subjects with Alzheimer's disease. The site of aluminum deposition within these cells was the neurofibrillary tangle itself, and not the "nuclear region," as we previously reported. Iron accumulation was also detected within neurofibrillary tangles. Evaluation for the accumulation of other elements within the tangle-bearing neurons failed to reveal any other metallic element as being consistently present. In addition, probe sites directed to neurons identified in snap-frozen cryostat sections from 2 subjects with Alzheimer's disease revealed similar spectra with prominent aluminum-related peaks, confirming that our findings are not related to exogenous contamination through fixation, embedding, or other procedures prior to analysis. This study further confirms the association of aluminum and neurofibrillary tangle formation in Alzheimer's disease. PMID- 1637137 TI - Cortically evoked motor responses in patients with Xp22.3-linked Kallmann's syndrome and in female gene carriers. AB - Patients with Kallmann's syndrome show hypothalamic hypogonadism, hyposmia, and congenital mirror movements. As a correlate, a defect of gonadotropic neuron migration into the brain was recently detected. Considering abnormal outgrowth of neurons also as a possible substrate underlying mirror movements, we studied 3 patients and 2 asymptomatic female gene carriers from a kindred with proven linkage to Xp22.3, using focal transcranial magnetic stimulation of motor cortex hand areas with a figure-eight coil. In all 3 affected brothers, bilateral responses could be evoked almost simultaneously in their thenar muscles (slight latency differences were statistically insignificant). In contrast, the mother and the maternal aunt showed only unilateral, normal thenar responses, even with maximum tolerable stimulator output and high signal amplification. Correspondingly, mirror movements were present in the patients, but not in the gene carriers. Bilaterality of cortically evoked hand muscle responses and mirror movements, therefore, behaved as X-chromosomal recessive traits. A likely cause might be a disorder of neuronal outgrowth in the motor system, particularly of inhibitory callosal fibers. For normal anatomical development of the motor system, one intact Xp22.3 gene seems necessary. PMID- 1637138 TI - Collagen cross-linking of skin in patients with amyotrophic lateral sclerosis. AB - Collagen cross-links of skin tissue (left upper arm) from 11 patients with amyotrophic lateral sclerosis (ALS) and 9 age-matched control subjects were quantified. It was found that patients with ALS had a significant reduction in the content of an age-related, stable cross-link, histidinohydroxylysinonorleucine, that was negatively correlated with the duration of illness. The contents of sodium borohydride-reducible labile cross links, dehydro-hydroxylysinonorleucine and dehydro-histidinohydroxymerodesmosine, were significantly increased and were positively associated with the duration of illness (r = 0.703, p less than 0.05 and r = 0.684, p less than 0.05, respectively). The results clearly indicate that during the course of ALS, the cross-linking pathway of skin collagen runs counter to its normal aging, resulting in a "rejuvenation" phenomenon of skin collagen. Thus, cross-linking of skin collagen is affected in ALS. PMID- 1637139 TI - In vivo imaging of glucose consumption and lactate concentration in human gliomas. AB - Twenty patients with histologically confirmed gliomas were studied with positron emission tomography (PET) and proton magnetic resonance spectroscopy (1H-MRS). PET with 18F-2-fluoro-2-deoxy-D-glucose (FDG) provided tomograms of the metabolic rate of glucose. MRS images were obtained by combining volume-selective excitation with phase-encoded acquisition. With 32 x 32 gradient phase-encoding steps, an in-plane resolution of 7 x 7 mm was achieved. From this set of spectra, lactate maps were created and compared with PET maps of glucose metabolism. Maximum glucose metabolic rates within tumors (relative to metabolic rates of glucose in contralateral regions of the brain) were correlated significantly with maximum lactate concentrations (relative to N-acetyl aspartate peaks in the contralateral part of the brain). In 8 tumors, no lactate was detected, and in 7 of these the maximum glucose metabolic rate was below the median value. The tumor with the highest lactate concentration also had the highest glucose metabolic rate. The topographic relation between glucose metabolic rate and lactate concentration could be analyzed in 9 patients by three-dimensional alignment of the PET and MRS images. In that analysis, maximum lactate concentrations were often not found in the same location as maximum glucose metabolism, but lactate tended to accumulate in tumor cysts, necrotic areas, and the vicinity of the lateral ventricles. The combination of FDG PET and 1H-MRS imaging demonstrates details of the spatial relation between the two poles of nonoxidative glycolysis, glucose uptake and lactate deposition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637140 TI - Revised estimate of the prevalence of multiple sclerosis in the United States. AB - Using three adjustments, we have revised a 1976 prevalence count for multiple sclerosis in the United States. The adjustments were made to data from a US national survey; they used 1990 population projections from the US Bureau of the Census, and results of investigations conducted in Weld and Larimer Countries, Colorado, and Olmsted County, Minnesota. It is estimated that approximately 250,000 to 350,000 persons in the United States in 1990 had physician-diagnosed multiple sclerosis. PMID- 1637141 TI - Congenital hypomyelination neuropathy with arthrogryposis multiplex congenita. AB - A term male infant is described with an isolated disorder of peripheral myelination. At necropsy, the great majority of medium-to-large axons were unmyelinated. Electron microscopy showed normal axons and redundant lamination of basement membrane, suggestive of early onion bulb pathology. Immunohistochemistry of peripheral nerve showed deficiency of the myelin proteins P2 and P0, myelin basic protein, and myelin-associated glycoprotein. Arrest of peripheral myelination at the promyelin stage appears to be the origin of myelin deficiency. PMID- 1637142 TI - Familial amyloidotic polyneuropathy: report of patients heterozygous for the transthyretin Gly42 gene. AB - We studied 2 patients from a Japanese family with familial amyloidotic polyneuropathy (FAP). Their clinical features are similar to type 1 FAP, and the proband's rectal tissue contained amyloid that stained with antihuman transthyretin (TTR) antiserum. Direct DNA sequencing of the proband's TTR gene revealed a guanine-for-adenine substitution in the second base of codon 42, producing a glycine for glutamate substitution in the plasma protein. PMID- 1637143 TI - [The interpretation of morphometric data of 10- to 13-year-old school children from the survey year 1978 of the Braunschweig Longitudinal Study]. AB - The paper represents a cross-sectional study from a sample of 1800 out of 3000 school-children from the Braunschweiger Langsschnitt. In this methodical approach we first eliminate approximately the influence of age and stature on the raw data from all body measurements with regression equations. The transformed data were attached to three "types" named 'below normal', 'normal', and 'above normal', in course of which 'normal' means all cases in the range of the standard deviation, whereas the two other "types" are corresponding to the adjacent ranges of values. Subsequently each transformation on the mean of age and stature a discriminant analysis has been performed grouping the cases by the "types" of the width of pelvis, resp. shoulders. There were found great influences of the stature on the chosen measures of width in our investigated class of age. They could be made clear alone by using allometrical methods. Only before correction of the body height the given grouping is supported by other variables, at which different sets of variables dominate the discriminant functions for boys and girls. Out of this new aspects and considerations result for the understanding of the physique and the physique typologies, which would be significant in our opinion for acceleration phenomenon as well as for the comparative examinations on populations. PMID- 1637144 TI - [The early bronze age graveyards of Franzhausen I, lower Austria. 2. Demographic analysis]. AB - In a recent study of 714 graves of the Early Bronze Age cemetery, Franzhausen I, 658 individuals were demographically analysed. The masculinity rate and the mortality rate in the age groups were of similar order compared with estimates derived from other series of this period. On the base of a stationary population model, life tables were calculated showing life expectancy at birth to be 25.8 years and at the age of 20, 17.7 years. Also computed were: the crude death rate (Z = 38.8); and the population size (P = 31 or 65). The lack of infants were estimated by regressions (5q0 = 58%) and the results are discussed. PMID- 1637145 TI - Dermatoglyphics of the Efe pygmies. AB - This paper deals with the dermatoglyphics in a group of Efe Pygmies, especially with the quantitative traits of fingers, as well as with palmar dermatoglyphics. This material was collected by P. Schebesta in Zaire and was partially published already by J.A. Valsik in 1938. PMID- 1637146 TI - [Position on the publication of S. Ehrhardt (1990): Setukesen. A population group between Estonians and Russians in southeast Estonia. Homo 40, 159-175. Reflections on responsibility in anthropological works]. AB - The uncommented publication of data on Setukesen people (SE Estonia), which were collected in 1942, by the scientific journal Homo (40, 159-175, 1990) is remarkably unreceptive to discussions within the scientific community at large. Therefore some basic considerations on scientific ethics in anthropology are outlined. Unfortunately Homo has refused to publish this statement which was written on appointment of the advisory board of the German Society of Anthropology and Human Genetics. PMID- 1637147 TI - [The early bronze age graveyard of Franzhausen I, lower Austria. 3. Study of epigenetic characteristics]. AB - The epigenetic variants of 635 early Bronze Age individuals from Franzhausen I, Lower Austria, were studied. The main interest of this examination, besides getting data, was the calculation of frequencies and testing the variants for sex and age dependence. Additionally, intertraits and side-to-side correlation were discussed. The results showed that as much data as possible should be included for calculation. Even subadult individuals could be adopted in the analysis if facts of growth and formative years are considered. Sex and intertrait correlation are less important for population comparison, but they have considerable consequences for intrapopulation calculation. PMID- 1637148 TI - [Sexual dimorphism of tooth crown diameters. A contribution to the determination of the sex of subadult individuals from the early bronze age graveyard of Franzhausen I, lower Austria]. AB - In this paper, the sexual differences between mesio-distal and bucco-lingual diameters of deciduous and permanent teeth of an Early Bronze Age population from Franzhausen are presented. Data from a total of 172 (85 male and 87 female) subadult individuals was collected. The presumptive sex determination needed for this investigation could be achieved because of specific burial rites that characterize the Unterwolbling culture south of the Danube. The averages of both the deciduous and permanent teeth show that female individuals possess altogether teeth of smaller dimensions. The differences are, for a few permanent teeth, statistically highly significant. Using these to calculate discriminant analyses based on differing variable sets, a correct sex assignment was achieved in 81% to 75% of all cases. For the purposes of sexual diagnosis, a function combining only three measurements (MD and BL diameters of upper canine and BL diameter of the first upper molar) was 80% successful. PMID- 1637149 TI - Food habits and dental disease in an iron-age population. AB - Tooth diseases and wear record valuable information on diet and methods of food preparation in past human populations. In this paper the teeth of an Iron-Age population (Monte Bibele, Bologna) are analyzed to reconstruct their nutritional situation. The analysis of caries frequency and distribution indicates a level of carbohydrate consumption which is consistent with an agricultural way of life. The presence of calculus indicates that proteins were present in the diet of the Monte Bibele population. The frequency of antemortem tooth loss and of dental abscesses is in harmony with the results of the analysis of caries and calculus. The examination of dental wear suggests the presence of a substantial vegetable component in the diet. From the analysis of the dental characteristics one can conclude that the population of Monte Bibele had a prevalent agricultural economy. The presence of some diachronic variations in the distribution of the examined characters suggest changes in the diet in the course of time. PMID- 1637150 TI - [The color and structure of the human iris. 1. Morphological studies]. AB - The material basis of this investigation consists of empirical findings and colour photographs of the irises of 200 pairs of twins and 100 control pairs. For the morphological investigation first-born twins and control persons are combined to constitute a comparative group of 400 non-related testees. Research by means of the iris microscope and the evaluation of standardized iris photographs led to the development of a catalogue of features which describes 10 iris characteristics for the iris colour and 20 for the iris structure. For each feature different degrees of markedness are defined and their frequency is determined. Similarly, intraindividual right/left and sex differences as well as age-dependencies and the relation between the features are examined. The setting up of features includes outlining an iris-colour class system in order to render a better and more practicable determination of eye colour possible. As a substitute for Martin/Schulz's table of eye-colour, which describes only eye colour phenomena, 4 iris-colour classes are set up whose main criterion of classification is the quantity of pigment. When we consider the testees of all age classes, sex differences have no statistical relevance as for iris colour. Only in the case of male testees may an intensive decrease of blue and brown iris colour in favour of combination colours (yellow pigment colours in particular) be observed during the phase of puberty. Therefore, the brightening postulated in the relevant literature can be confirmed. With regard to female testees, in contrast, pigment shifting is of no statistical relevance. After a slight brightening the irises numerically re-darken at the adult-stage to the initial child level, i.e. they become "dark again" rather than just become "darker". Within the iris structure only the characteristics of the anterior stroma leaf show sex differences. They are, however, only weakly marked and can be described merely as a trend. Over the whole range of the age classes, there are no outstanding structural differences. The different iris characteristics concerning iris colour stand in a significant relation to each other. When we consider the statistically relevant relations between structural features, it becomes clear that particularly reduced and particularly intact iris characteristics correlate. Thus, we can distinguish between an intact type of iris and a reduced one. Three quarters of the testees, however, combine reduced and intact properties with medium degrees of markedness.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1637151 TI - Ethanol production from cellobiose, amorphous cellulose, and crystalline cellulose by recombinant Klebsiella oxytoca containing chromosomally integrated Zymomonas mobilis genes for ethanol production and plasmids expressing thermostable cellulase genes from Clostridium thermocellum. AB - The Zymomonas mobilis genes for ethanol production have been integrated into the chromosome of Klebsiella oxytoca M5A1. The best of these constructs, strain P2, produced ethanol efficiently from cellobiose in addition to monomeric sugars. Utilization of cellobiose and cellotriose by this strain eliminated the requirement for external beta-glucosidase and reduced the amount of commercial cellulase needed to ferment Solka Floc SW40 (primarily crystalline cellulose). The addition of plasmids encoding endoglucanases from Clostridium thermocellum resulted in the intracellular accumulation of thermostable enzymes as coproducts with ethanol during fermentation. The best of these, strain P2(pCT603T) containing celD, was used to hydrolyze amorphous cellulose to cellobiose and produce ethanol in a two-stage process. Strain P2(pCT603T) was also tested in combination with commercial cellulases. Pretreatment of Solka Floc SW40 at 60 degrees C with endoglucanase D substantially reduced the amount of commercial cellulase required to ferment Solka Floc. The stimulatory effect of the endoglucanase D pretreatment may result from the hydrolysis of amorphous regions, exposing additional sites for attack by fungal cellulases. Since endoglucanase D functions as part of a complex in C. thermocellum, it is possible that this enzyme may complex with fungal enzymes or bind cellulose to produce a more open structure for hydrolysis. PMID- 1637152 TI - Microbial oxidation of oleic acid. AB - Resting cells of Saccharomyces cerevisiae (baker's yeast, type II; Sigma) were used to convert oleic acid into 10-hydroxyoctadecanoic acid with a 45% yield. Nocardia aurantia (ATCC 12674), Nocardia sp. (NRRL 5646), and Mycobacterium fortuitum (UI 53378) all converted oleic acid into 10-oxo-octadecanoic acid with 65, 55, and 80% yields, respectively. Structures of all metabolites were suggested by 1H and 13C nuclear magnetic resonance and by infrared and mass spectrometry. Structures of isomeric hydroxystearate and oxostearate derivatives and the stereochemical purity of hydroxystearates are difficult to prove unambiguously unless authentic standard compounds are available for spectral comparison. We describe the use of the chemical Baeyer-Villiger oxidation technique with 10-oxo-octadecanoic acid followed by mass spectral analysis of neutral extracts as a simple method to confirm the position of oxo-functional groups in the structures of fatty acid ketones. We further introduce a simple method based on 1H nuclear magnetic resonance analysis of diastereomeric S-(+)-O acetylmandelate esters of hydroxystearates as a means of ascertaining stereochemical purities of hydroxy fatty acids. PMID- 1637153 TI - Limited degradation of chlorophenols by anaerobic sludge granules. AB - To better understand the fate of chlorophenols treated in upflow anaerobic sludge bed reactors, we examined the ability of sludge granules from such bioreactors to degrade two trichlorophenols and one dichlorophenol in batch incubations under controlled conditions. Biodegradation was primarily limited to two distinct activities, reductive dehalogenation of ortho- and of meta-chlorine substituents. Both 3- and 4-monochlorophenol were persistent degradation products, while 2 monochlorophenol was further degraded. We also examined factors potentially affecting the rate and extent of 2,3,6-trichlorophenol degradation. An initial concentration of up to 1.75 mM (346 mg/liter) was dehalogenated. At that concentration, dehalogenation was partially inhibited but methanogenesis from formate was not. The initial concentration affected both the extent of dehalogenation and which products were detected. The maximum dechlorination rate observed was 1.4 mumol of Cl- h-1 g of volatile suspended solids-1. Dechlorination had a temperature optimum of 50 degrees C, was inhibited by added electron acceptors, and was not appreciably affected by added electron donors. The availability of electron acceptors and electron donors did not affect the extent of chlorophenol degradation. These particular sludge granules do not appear to be capable of mineralizing phenols with meta- or para-chlorine substituents. PMID- 1637154 TI - Purification and characterization of two serine carboxypeptidases from Aspergillus niger and their use in C-terminal sequencing of proteins and peptide synthesis. AB - A procedure was developed to prepare in large amounts two carboxypeptidases, CPD I and CPD-II, from Aspergillus niger. They were each shown to be serine proteases and single-chain monomers with molecular masses of ca. 81 kDa and containing 22% carbohydrates. Amino acid analysis, carbohydrate determination, and N-terminal sequencing (20 to 25 residues) were performed on each enzyme. CPD-I showed sequence homologies with malt carboxypeptidase II, while the N terminus of CPD-II was different from that of any known serine carboxypeptidase. Like carboxypeptidase Y from Saccharomyces cerevisiae and carboxypeptidase III from malt, CPD-II contained a free sulfhydryl group that could play a role in catalysis. Both A. niger enzymes had pH optima of about 4 and were unstable above pH 7. Their specificities for substrate positions P1 and P'1 were characterized by use of, as substrates, a series of N-blocked amino acid esters and dipeptides. Both enzymes were specific for Arg, Lys, and Phe in P1. CPD-I preferred hydrophobic residues in P'1, while CPD-II was highly specific for Arg and Lys in this position. Each displayed an original specificity when P1 and P'1 were considered together. The specificities were also studied by analyzing the time course of the release of amino acids from eight different peptides of various lengths. CPD-I and CPD-II appeared to be quite suitable for C-terminal sequence studies as well as for the synthesis of peptide bonds. The latter was studied with two peptide esters as aminolysis substrates and a series of amino acid amides as nucleophiles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637155 TI - Structure, organization, and transcription of a cellobiohydrolase gene cluster from Phanerochaete chrysosporium. AB - Restriction mapping and sequence analysis of cosmid clones revealed a cluster of three cellobiohydrolase genes in Phanerochaete chrysosporium. P. chrysosporium cbh1-1 and cbh1-2 are separated by only 750 bp and are located approximately 14 kb upstream from a cellulase gene previously cloned from P. chrysosporium (P. Sims, C. James, and P. Broda, Gene 74:411-422, 1988). Within a well-conserved region, the deduced amino acid sequences of P. chrysosporium cbh1-1 and cbh1-2 are, respectively, 80 and 69% homologous to that of the Trichoderma reesei cellobiohydrolase I gene. The conserved cellulose-binding domain typical of microbial cellulases is absent from cbh1-1. Transcript levels of the three P. chrysosporium genes varied substantially, depending on culture conditions. cbh1-1 and cbh1-2 were not induced in the presence of cellulose, nor did they appear to be subject to glucose repression. Therefore, aspects of the chromosomal organization, structure, and transcription of these genes are unlike those of any previously described cellulase genes. PMID- 1637156 TI - Use of repetitive (repetitive extragenic palindromic and enterobacterial repetitive intergeneric consensus) sequences and the polymerase chain reaction to fingerprint the genomes of Rhizobium meliloti isolates and other soil bacteria. AB - The distribution of dispersed repetitive DNA (repetitive extragenic palindromic [REP] and enterobacterial repetitive intergenic consensus [ERIC]) sequences in the genomes of a number of gram-negative soil bacteria was examined by using conserved primers corresponding to REP and ERIC sequences and the polymerase chain reaction (PCR). The patterns of the resulting PCR products were analyzed on agarose gels and found to be highly specific for each strain. The REP and ERIC PCR patterns of a series of Rhizobium meliloti isolates, previously ordered in a phylogenetic tree based on allelic variations at 14 enzyme loci (B. D. Eardly, L. A. Materon, N. H. Smith, D. A. Johnson, M. D. Rumbaugh, and R. K. Selander, Appl. Environ. Microbiol. 56:187-194), were determined. Isolates which had been postulated to be closely related by multilocus enzyme electrophoresis also revealed similar REP and ERIC PCR patterns, suggesting that the REP and ERIC PCR method is useful for the identification and classification of bacterial strains. PMID- 1637157 TI - Influence of ecosystematic factors on survival of Escherichia coli after large scale release into lake water mesocosms. AB - Mass cultures of an Escherichia coli K-12 strain were released into exposed mesocosms in a eutrophic lake. The release was performed with and without additional input of the E. coli culture medium to stimulate the scenario of leakage of a production fermenter on one hand and to compare the influence of the added organic nutrients with that of the added strain on the other hand. The survival of the introduced strain and the influence on ecological processes in the mesocosms were monitored for 10 weeks after release. For comparison, survival of the strain in microcosms with sterile lake water was also monitored. Survival of the strain was determined by means of immunofluorescence and growth on selective agar medium. In lake mesocosms, E. coli showed a rapid and constant dieback during the first week. After 4 days, cells were mostly restricted to particles, which seemed to provide niches for survival. From the second week onward, survival was improved in mesocosms with culture medium added. In microcosms with sterile lake water, plate counts of E. coli showed a strong decrease within 2 weeks, while total cell numbers remained approximately the same. The rapid elimination of E. coli from the free-water phase of the mesocosms was probably due to the combined effect of the inability to grow in lake water and grazing. The better survival of E. coli (mainly on particles) in mesocosms with added medium was attributed to the medium-induced enhancement of primary production, which was the source of a large quantity of particles. These particles, in turn, may have functioned as niches for prolonged survival as well as transport vehicles for sedimentation of the E. coli cells. PMID- 1637158 TI - Biosorption of dichlorodiphenyltrichloroethane and hexachlorobenzene in groundwater and its implications for facilitated transport. AB - The potential for enhanced mobility of hydrophobic pollutants by cotransport with bacteria in saturated soils was evaluated from measurements of biosorption of 14C labeled hexachlorobenzene and dichlorodiphenyltrichloroethane (DDT) to five strains of soil and sewage bacteria. The sorption process could be described by a linear partition equation and appeared to be reversible, but desorption kinetics were slow and/or partly irreversible. The DDT partition coefficients varied with equilibration time, possibly reflecting DDT-induced changes in the physiology of the bacteria. The partition coefficients, normalized to the masses of the bacteria, ranged from 250 to 14,000 for live cells, but the largest coefficients were associated with autoclaved cells of a Pseudomonas sp. The sorptive capacity of the bacterial biomass was greater for DDT than for hexachlorobenzene but was not correlated to overall bacterial hydrophobicity, measured by hydrophobic interaction chromatography. In a column study, 1.2 x 10(9) cells of a Bacillus sp. strain per ml enhanced DDT transport about 8-fold, whereas an advective dispersive-sorptive equilibrium model for two mobile phases, water and free living bacteria, suggested a 14-fold enhancement, based on the DDT partition coefficient. The disagreement was in part due to a retarded nonequilibrium movement of the bacteria. Model calculations based on literature data covering a wide range of organisms and compounds suggested that 10(6) cells ml-1 would increase the mobility of very hydrophobic compounds (log octanol-water partition coefficient [K(ow) of greater than or equal to 6), whereas higher densities of bacteria (10(8) cells ml-1) would have a significant impact on compounds with a log K(ow) of greater than or equal to 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637159 TI - Biodegradation of polycyclic aromatic hydrocarbons by new isolates of white rot fungi. AB - Eight rapid Poly R-478 dye-decolorizing isolates from The Netherlands were screened in this study for the biodegradation of polycyclic aromatic hydrocarbons (PAH) supplied at 10 mg liter(-1). Several well-known ligninolytic culture collection strains, Phanerochaete chrysosporium BKM-F-1767, Trametes versicolor Paprican 52, and Bjerkandera adusta CBS 595.78 were tested in parallel. All of the strains significantly removed anthracene, and nine of the strains significantly removed benzo(a)pyrene beyond the limited losses observed in sterile liquid and HgCl2-poisoned fungus controls. One of the new isolates, Bjerkandera sp. strain Bos 55, was the best degrader of both anthracene and benzo(a)pyrene, removing 99.2 and 83.1% of these compounds after 28 days, respectively. Half of the strains, exemplified by strains of the genera Bjerkandera and Phanerochaete, converted anthracene to anthraquinone, which was found to be a dead-end metabolite, in high yields. The extracellular fluids of selected strains were shown to be implicated in this conversion. In contrast, four Trametes strains removed anthracene without significant accumulation of the quinone. The ability of Trametes strains to degrade anthraquinone was confirmed in this study. None of the strains accumulated PAH quinones during benzo(a)pyrene degradation. Biodegradation of PAH by the various strains was highly correlated to the rate by which they decolorized Poly R-478 dye, demonstrating that ligninolytic indicators are useful in screening for promising PAH-degrading white rot fungal strains. PMID- 1637160 TI - Applications of a colorimetric plate assay for soluble methane monooxygenase activity. AB - A straightforward method is described for screening methanotrophic colonies for soluble methane monooxygenase (sMMO) activity on solid media. Such activity results in the development of a colored complex between 1-naphthol, which is formed when sMMO reacts with naphthalene, and o-dianisidine (tetrazotized). Methanotrophic colonies expressing sMMO turned deep purple when exposed successively to naphthalene and o-dianisidine. The method was evaluated within the contexts of two potential applications. The first was for the enumeration of Methylosinus trichosporium OB3b in a methane-amended, unsaturated soil column dedicated to vinyl chloride treatment. The second application was for the isolation and enumeration of sMMO-bearing methanotrophs from sanitary landfill soils. The technique was effective in both applications. PMID- 1637161 TI - Biodegradation of mixtures of substituted benzenes by Pseudomonas sp. strain JS150. AB - Pseudomonas sp. strain JS150 was isolated as a nonencapsulated variant of Pseudomonas sp. strain JS1 that contains the genes for the degradative pathways of a wide range of substituted aromatic compounds. Pseudomonas sp. strain JS150 grew on phenol, ethylbenzene, toluene, benzene, naphthalene, benzoate, p hydroxybenzoate, salicylate, chlorobenzene, and several 1,4-dihalogenated benzenes. We designed experiments to determine the conditions required for induction of the individual pathways and to determine whether multiple substrates could be biodegraded simultaneously. Oxygen consumption studies with whole cells and enzyme assays with cell extracts showed that the enzymes of the meta, ortho, and modified ortho cleavage pathways can be induced in strain JS150. Strain JS150 contains a nonspecific toluene dioxygenase with a substrate range similar to that found in strains of Pseudomonas putida. The presence of the dioxygenase along with multiple pathways for metabolism of substituted catechols allows facile extension of the growth range by spontaneous mutation and degradation of mixtures of substituted benzenes and phenols. Chlorobenzene-grown cells of strain JS150 degraded mixtures of chlorobenzene, benzene, toluene, naphthalene, trichloroethylene, and 1,2- and 1,4-dichlorobenzenes in continuous culture. Under similar conditions, phenol-grown cells degraded a mixture of phenol, 2-chloro-, 3 chloro, and 2,5-dichlorophenol and 2-methyl- and 3-methylphenol. These results indicate that induction of appropriate biodegradative pathways in strain JS150 permits the biodegradation of complex mixtures of aromatic compounds. PMID- 1637162 TI - Numerical taxonomy of gram-negative, nonmotile, nonfermentative bacteria isolated during chilled storage of lamb carcasses. AB - A numerical taxonomic study using 75 characters was performed with 132 strains of gram-negative, nonmotile, nonfermentative bacteria selected on the basis of lack of motility and Gram reaction among 1,200 cultures isolated during aerobic storage of lamb carcasses. At the 80% similarity level (SSM), eight clusters were formed. Strains in clusters 1 to 6 could be identified as members of the family Moraxellaceae and, more specifically, as members of the Psychrobacter-[Moraxella] phenylpyruvica subgroup. Of these strains, clusters 1 and 2 (88 strains) were identified as [Moraxella] phenylpyruvica and cluster 3 (15 strains) was identified as Psychrobacter immobilis. Clusters 4, 5, and 6 were not identifiable with any species. Clusters 7 and 8 consisted of 14 strains considered nonmotile variants of Pseudomonas fragi. The highest separation indices corresponded to acid production from certain carbohydrates (melibiose, L-arabinose, and cellobiose). Although strains of Psychrobacter-Moraxella clusters were relatively frequently identified at the completion of slaughter, very few cultures were detected on spoiled carcasses. It appears, therefore, that this group of organisms has only low spoilage potential. PMID- 1637163 TI - Depletion of proton motive force by nisin in Listeria monocytogenes cells. AB - The basal proton motive force (PMF) levels and the influence of the bacteriocin nisin on the PMF were determined in Listeria monocytogenes Scott A. In the absence of nisin, the interconversion of the pH gradient (Z delta pH) and the membrane potential (delta psi) led to the maintenance of a fairly constant PMF at -160 mV over the external pH range 5.5 to 7.0. The addition of nisin at concentrations of greater than or equal to 5 micrograms/ml completely dissipated PMF in cells at external pH values of 5.5 and 7.0. With 1 microgram of nisin per ml, delta pH was completely dissipated but delta psi decreased only slightly. The action of nisin on PMF in L. monocytogenes Scott A was both time and concentration dependent. Valinomycin depleted only delta pH, whereas nigericin and carbonyl cyanide m-chlorophenylhydrazone depleted only delta psi, under conditions in which nisin depleted both. Four other L. monocytogenes strains had basal PMF parameters similar to those of strain Scott A. Nisin (2.5 micrograms/ml) also completely dissipated PMF in these strains. PMID- 1637164 TI - Determination of plasmid DNA concentration maintained by nonculturable Escherichia coli in marine microcosms. AB - The concentration of plasmid pBR322 DNA in nonculturable Escherichia coli JM83 was measured to determine whether the plasmid concentration changed during survival of E. coli in marine and estuarine water. E. coli JM83 containing the plasmid pBR322 was placed in both sterile seawater and sterile estuarine water and analyzed for survival (i.e., culturability) and plasmid maintenance. The concentration of pBR322 DNA remained stable in E. coli JM83 for 28 days in an artificial seawater microcosm, even though nonculturability was achieved within 7 days. E. coli JM83 incubated in sterile natural seawater or sterile estuarine water did not reach nonculturability within 30 days. Under all three conditions, plasmid pBR322 DNA was maintained at approximately the initial concentration. Cloning of DNA into the plasmid pUC8 did not alter the ability of E. coli to maintain vector plasmid DNA, even when the culture was in the nonculturable state, but the concentration of plasmid DNA decreased with time in the microcosm. We conclude that E. coli is able to maintain plasmid DNA while in the nonculturable state and that the concentration at which the plasmid is maintained appears to be dependent upon the copy number of the plasmid and/or the presence of foreign DNA. PMID- 1637165 TI - Reductive dechlorination of chlorophenols by a pentachlorophenol- acclimated methanogenic consortium. AB - Anaerobic digester sludge fed 5,300 mg of acetate per liter, 3.4 microM pentachlorophenol, and nutrients for 10 days biotransformed pentachlorophenol by sequential ortho dechlorinations to produce 2,3,4,5-tetrachlorophenol and 3,4,5 trichlorophenol. Upon acclimation to 3.4 microM pentachlorophenol for 6 months, the methanogenic consortium removed chlorines from the ortho, meta, and para positions of pentachlorophenol and its reductive dechlorination products. Pentachlorophenol was degraded to produce 2,3,4,5-tetrachlorophenol, 2,3,4,6 tetrachlorophenol, and 2,3,5,6-tetrachlorophenol. Dechlorination of 2,3,4,5 tetrachlorophenol produced 3,4,5-trichlorophenol, which was subsequently degraded to produce 3,4-dichlorophenol and 3,5-dichlorophenol. 2,3,4,6-Tetrachlorophenol was dechlorinated at the ortho and meta positions to produce 2,4,6 trichlorophenol and 2,4,5-trichlorophenol. 2,3,5,6-Tetrachlorophenol yielded 2,3,5-trichlorophenol, followed by production of 3,5-dichlorophenol. 2,4,6 Trichlorophenol was degraded to form 2,4-dichlorophenol, and 2,4,5 trichlorophenol was dechlorinated at two positions to form 2,4-dichlorophenol and 3,4-dichlorophenol. Of the three dichlorophenols produced (2,4-dichlorophenol, 3,4-dichlorophenol, and 3,5-dichlorophenol), only 2,4-dichlorophenol was degraded significantly within 3 weeks, to produce 4-chlorophenol. PMID- 1637166 TI - Combined subtraction hybridization and polymerase chain reaction amplification procedure for isolation of strain-specific Rhizobium DNA sequences. AB - A novel subtraction hybridization procedure, incorporating a combination of four separation strategies, was developed to isolate unique DNA sequences from a strain of Rhizobium leguminosarum bv. trifolii. Sau3A-digested DNA from this strain, i.e., the probe strain, was ligated to a linker and hybridized in solution with an excess of pooled subtracter DNA from seven other strains of the same biovar which had been restricted, ligated to a different, biotinylated, subtracter-specific linker, and amplified by polymerase chain reaction to incorporate dUTP. Subtracter DNA and subtracter-probe hybrids were removed by phenol-chloroform extraction of a streptavidin-biotin-DNA complex. NENSORB chromatography of the sequences remaining in the aqueous layer captured biotinylated subtracter DNA which may have escaped removal by phenol-chloroform treatment. Any traces of contaminating subtracter DNA were removed by digestion with uracil DNA glycosylase. Finally, remaining sequences were amplified by polymerase chain reaction with a probe strain-specific primer, labelled with 32P, and tested for specificity in dot blot hybridizations against total genomic target DNA from each strain in the subtracter pool. Two rounds of subtraction amplification were sufficient to remove cross-hybridizing sequences and to give a probe which hybridized only with homologous target DNA. The method is applicable to the isolation of DNA and RNA sequences from both procaryotic and eucaryotic cells. PMID- 1637167 TI - Monoclonal antibody-colony immunoblot method specific for isolation of Pediococcus acidilactici from foods and correlation with pediocin (bacteriocin) production. AB - BALB/c mice were immunized with broken, heat-killed cells of Pediococcus acidilactici H. After murine cell fusions, one monoclonal antibody (MAb), Ped 2B2, was selected on the basis of its positive reaction with seven of seven strains tested in an enzyme-linked immunosorbent assay with whole cells of P. acidilactici. The MAb Ped-2B2 did not show any cross-reactions with other lactic acid bacteria or other gram-positive or gram-negative organisms. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot (immunoblot) analysis of surface proteins of P. acidilactici indicated that Ped-2B2 reacted with a protein of 116 kDa. MAb Ped-2B2 was used as a probe to isolate Pediococcus species from fermented-meat products by colony immunoblotting. A total of 18 Ped 2B2-reactive Pediococcus spp. isolates were isolated from eight food samples and assayed for bacteriocin production. All of the isolates produced bacteriocins which were heat stable, proteinaceous, and inhibitory to Lactobacillus plantarum NCDO 955. Biochemical characterization of these isolates indicated that they were all P. acidilactici. PMID- 1637168 TI - Immunogold and fluorescein immunolabelling of Legionella pneumophila within an aquatic biofilm visualized by using episcopic differential interference contrast microscopy. AB - Biofilms containing diverse microflora were developed in tap water on glass and polybutylene surfaces. Legionella pneumophila within the biofilms was labelled with monoclonal antibodies and visualized with immunogold or fluorescein isothiocyanate conjugates. Development of a differential interference contrast technique in an episcopic mode enabled simultaneous visualization of the total biofilm flora and gold-labelled legionellae. The legionellae occurred in microcolonies within the biofilm in the absence of amoebae, suggesting that the bacterial consortium was supplying sufficient nutrients to enable legionellae to grow extracellularly within the biofilm. PMID- 1637169 TI - Vitamin B12-dependent propionate production by the ruminal bacterium Prevotella ruminicola 23. AB - When Prevotella ruminicola 23 was grown in a defined medium containing a vitamin mixture, significant amounts of propionate were formed. Succinate and acetate were the major fermentation acids produced when vitamins were omitted, and further experiments demonstrated that propionate formation was dependent on vitamin B12. When the organism was grown in continuous culture at dilution rates of less than 0.20 h-1, propionate and acetate were the predominant fermentation products and little succinate was formed when vitamin B12 was present. However, at higher dilution rates, propionate formation declined and succinate accumulated. Since cell protein yields were reduced 15 to 25% in the absence of vitamin B12, the pathway for propionate formation may contain an energy conserving step. PMID- 1637170 TI - Roles of arginine in growth of Clostridium botulinum Okra B. AB - Group I strains of Clostridium botulinum are known to degrade arginine by the arginine deiminase pathway. We have found that C. botulinum Okra B consumed a level of arginine (20 g/liter) higher than the basal requirement for growth (3 g/liter). Arginine was probably the preferred source of nitrogen for biosynthesis but did not serve as a major source of energy. Citrulline and proline were produced as major fermentation products in media containing high levels of arginine, but in media with basal amounts of arginine these products were produced in lower quantities during growth and were later reassimilated. The results indicate that C. botulinum Okra B changes its metabolism during consumption of surplus arginine, and this change is associated with toxin repression, formation of citrulline and proline as end products, and possibly resistance to environmental stresses such as increased acidity and osmolarity. PMID- 1637171 TI - Changes in fatty acid branching and unsaturation of Streptomyces griseus and Brevibacterium fermentans as a response to growth temperature. AB - Streptomyces griseus showed three different modes of changing fatty acids in response to temperature change. In Brevibacterium fermentans, two such responses were found. The responses involved changes in fatty acid branching, unsaturation, or chain length, depending on growth temperature range. Changes in unsaturation of branched-chain acids were characteristic at low growth temperatures. PMID- 1637172 TI - Altered proteoglycan synthesis via the false acceptor pathway can be dissociated from beta-D-xyloside inhibition of proliferation. AB - beta-D-Xylosides have been used to perturb proteoglycan (PG) synthesis to elucidate the function of PGs in a number of cellular processes, including proliferation, migration, and differentiation. This study was designed to examine whether specific xylosides affect the proliferation of several different cell types and, if so, whether this effect is dependent on altered PG synthesis via the false acceptor pathway. Both methylumbelliferyl beta-D-xylopyranoside and p nitrophenyl beta-D-xylopyranoside (PNP beta-xyloside) inhibit cell proliferation and modulate PG synthesis; however, the alpha form of PNP xyloside which does not perturb PG synthesis inhibits the proliferation of cultured cells on a molar basis equally as well as the beta form. Conversely, beta-methyl xylopyranoside stimulates the synthesis of free glycosaminoglycan chains equally as well as PNP beta-xyloside and yet has no measurable effect on cell proliferation at comparable doses, indicating that cells can grow normally while experiencing disruption of their proteoglycan metabolism. At doses ranging from 0.5 to 5 mM, PNP beta-xyloside arrests cells in the G1 phase of the cell cycle at the same time point as serum starvation. It also delays the exist of cycling cells from the S phase. This treatment is not cytotoxic and is rapidly reversed by the replacement of PNP beta-xyloside containing medium with control medium. Dimethyl sulfoxide, the most commonly used solvent for beta-xyloside in proteoglycan studies, potentiates the inhibitory effect of PNP beta-xyloside on cell proliferation. These results indicate that the perturbation of PG synthesis via the false acceptor pathway can be uncoupled from control of cell proliferation. PMID- 1637173 TI - Mitochondrial damage and its role in causing hepatocyte injury during stimulation of lipid peroxidation by iron nitriloacetate. AB - Incubation of isolated rat hepatocytes with 0.1 mM iron nitrilotriacetic acid (FeNTA) caused a rapid rise in lipid peroxidation followed by a substantial increase in trypan blue staining and lactate dehydrogenase release, but did not affect the protein and non-protein thiol content of the cells. Hepatocyte death was preceded by the decline of mitochondrial membrane potential, as assayed by rhodamine 123 uptake, and by the depletion of cellular ATP. Chelation of extracellular Ca2+ by ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid or inhibition of Ca2+ cycling within the mitochondria by LaCl3 or cyclosporin A did not prevent the decline of rhodamine 123 uptake. On the other hand, a dramatic increase in the conjugated diene content was observed in mitochondria isolated from FeNTA-treated hepatocytes. Oxidative damage of mitochondria was accompanied by the leakage of matrix enzymes glutamic oxalacetic aminotransferase (GOT) and glutamate dehydrogenase (GLDH). The addition of the antioxidant N,N'-diphenylphenylene diamine (DPPD) completely prevented GOT and GLDH leakage, inhibition of rhodamine 123 uptake, and ATP depletion induced by FeNTA, indicating that Ca(2+)-independent alterations of mitochondrial membrane permeability consequent to lipid peroxidation were responsible for the loss of mitochondrial membrane potential. DPPD addition also protected against hepatocyte death. Similarly hepatocytes prepared from fed rats were found to be more resistant than those obtained from starved rats toward ATP depletion and cell death caused by FeNTA, in spite of undergoing a comparable mitochondrial injury. A similar protection was also observed following fructose supplementation of hepatocytes isolated from starved rats, indicating that the decline of ATP was critical for the development of FeNTA toxicity. From these results it was concluded that FeNTA-induced peroxidation of mitochondrial membranes impaired the electrochemical potential of these organelles and led to ATP depletion which was critical for the development of irreversible cell injury. PMID- 1637174 TI - Inhibition of glutathione transferase pi from human placenta by 1-chloro-2,4 dinitrobenzene occurs because of covalent reaction with cysteine 47. AB - Human placenta glutathione transferase pi is irreversibly inhibited when incubated with 1-chloro-2,4-dinitrobenzene (CDNB) in the absence of the cosubstrate glutathione. The enzyme is protected against CDNB inactivation by the presence of S-methylglutathione and glutathione. The kinetics of inactivation is pseudo-first-order with k(obs) = 0.04 min-1 when 44 microM enzyme is incubated in presence of 1 mM CDNB at pH 6.5. The inhibition is saturable with respect to the CDNB concentration and the enzyme-CDNB complex shows a K(i) = 2.7 mM. Concomitant to the inhibition process is formation of an absorption band at 340 nm. After trypsin digestion and HPLC analysis, the CDNB-reacted enzyme gives a single peptide absorbing at 340 nm. Automated Edman degradation of this peptide indicates cysteine 47 to be the residue alkylated by CDNB. PMID- 1637175 TI - Plant sterol biosynthesis: novel potent and selective inhibitors of cytochrome P450-dependent obtusifoliol 14 alpha-methyl demethylase. AB - The R-(-) isomer of methyl 1-(2,2-dimethylindan-1-yl)imidazole-5-carboxylate (CGA 214372; 2) strongly inhibited P450-dependent obtusifoliol 14 alpha-demethylase (P450OBT.14DM) (I50 = 8 x 10(-9) M, I50/Km = 5 x 10(-5) in a maize (Zea mays) microsomal preparation. Kinetic studies indicated uncompetitive inhibition with respect to obtusifoliol. The corresponding S-(+) isomer was a 20-fold weaker inhibitor for P450OBT.14DM. The molecular features of a variety of analogues of 2 were related to their potency as inhibitors of P450OBT.14DM in vitro, allowing delineation of the key structural requirements governing inhibition of the demethylase. CGA 214372 proved to have a high degree of selectivity for P450OBT.14DM. This allowed easy distinction of this activity from other P450 dependent activities present in the maize microsomal preparation and gave strong evidence that P450OBT.14DM is a herbicidal target. Microsomal maize P450OBT.14DM and yeast P450LAN.14DM, the only known examples of P450-dependent enzymes carrying out an identical metabolic function in different eukaryotes, showed distinct inhibition patterns with CGA 214372 and ketoconazole, a substituted imidazole anti-mycotic. PMID- 1637176 TI - Enantioselective inhibition of human leukocyte elastase. AB - (RS)-Diethyl-2-benzyl-succinate was resolved using alpha-chymotrypsin. The two enantiomers were then elaborated to yield (S)-(+) and (R)-(-)-3-benzyl-N-[(methyl sulfonyl)oxy]succinimide and the inhibitory activity of the two enantiomers toward human leukocyte elastase was subsequently determined. The k2/KI values for the R and S isomers were found to be 330 and 1500 M-1 s-1, respectively. PMID- 1637177 TI - Lipid peroxidation and its inhibition in low density lipoproteins: quenching of cis-parinaric acid fluorescence. AB - The fluorescent polyunsaturated parinaric acid incorporated in LDL particles is highly sensitive to the concentration of peroxyl radicals in the aqueous medium, undergoing rapidly oxidative degradation, as detected by a quenching of fluorescence, without delay after radical generation in solution. Ascorbate, cysteine, and urate suppress the parinaric acid fluorescence decay promoted by peroxyl radicals generated at a constant rate (thermal decomposition of 2,2'-azo bis(2-amidino-propane hydrochloride)) in a concentration-dependent manner. The chain-breaking efficiencies of these antioxidants are evaluated from the time interval (inhibition period) of parinaric acid protection from oxidative degradation. The results correlate with the inhibition periods of LDL oxidation as monitored by O2 consumption. Therefore, the sensitive and simple parinaric acid assay can be used as a semiquantitative screening test for the detection of potentially important water-soluble chain-breaking antioxidants. Conversely to O2 consumption, the absence of any initial lag phase of probe degradation attests to the sensitivity of the assay. An improved methodology based on second-derivative spectroscopy to follow the formation of conjugated diene isomers directly in the preparation without the need for lipid extraction also confirms the sensitivity of this assay. To assess the usefulness of parinaric acid assay, strong chain breaking activities of caffeic and chlorogenic acids are reported. PMID- 1637178 TI - The heparin binding site of human extracellular-superoxide dismutase. AB - Extracellular-superoxide dismutase (EC-SOD) is a secretory glycoprotein that is major SOD isozyme in extracellular fluids. We revealed the possible structure of the carbohydrate chain of serum EC-SOD with the serial lectin affinity technique. The structure is a biantennary complex type with an internal fucose residue attached to asparagine-linked N-acetyl-D-glucosamine and with terminal sialic acid linked to N-acetyllactosamine. EC-SOD in plasma is heterogeneous with regard to heparin affinity and can be divided into three fractions: A, without affinity; B, with intermediate affinity; and C, with high affinity. It appeared that this heterogeneity is not dependent on the carbohydrate structure upon comparison of EC-SOD A, B, and C. No effect of the glycopeptidase F treatment of EC-SOD C on its heparin affinity supported the results. A previous report showed that both lysine and arginine residues probably at the C-terminal end, contribute to heparin binding. Recombinant EC-SOD C treated with trypsin or endoproteinase Lys C, which lost three lysine residues (Lys-211, Lys-212, and Lys-220) or one lysine residue (Lys-220) at the C-terminal end, had no or weak affinity for the heparin HPLC column, respectively. The proteinase-treated r-EC-SOD C also lost triple arginine residues which are adjacent to double lysine residues. These results suggest that the heparin-binding site may occur on a "cluster" of basic amino acids at the C-terminal end of EC-SOD C. EC-SOD is speculated to be primarily synthesized as type C, and types A and B are probably the result of secondary modifications. It appeared that the proteolytic cleavage of the exteriorized lysine- and arginine-rich C-terminal end in vivo is a more important contributory factor to the formation of EC-SOD B and/or EC-SOD A. PMID- 1637179 TI - The activity of pyruvate carrier in a reconstituted system: substrate specificity and inhibitor sensitivity. AB - The pyruvate carrier, of molecular mass 34 kDa, was purified from mitochondria isolated from rat liver, rat brain, and bovine heart, by affinity chromatography on immobilized 2-cyano-4-hydroxycinnamate. Its activity after reconstitution in phosphatidylcholine vesicles was measured either as uptake of [1-14C]pyruvate or as exchange with different 2-oxoacids. All preparations exhibited similar apparent Km values for pyruvate, but somewhat different V(max) values. The ability to exchange different anions of physiological significance, including branched-chain 2-oxoacids, confirmed the known substrate specificity described for the pyruvate carrier in mitochondria. The sensitivity of pyruvate transport toward phenylglyoxal suggested an important role of arginyl residues in the transport activity, while a role of lysyl and histidyl residues was not confirmed. PMID- 1637180 TI - beta-Carotene and alpha-tocopherol are synergistic antioxidants. AB - The possibility of a cooperative interaction between fat-soluble antioxidants is examined in a membrane model. A combination of beta-carotene and alpha-tocopherol results in an inhibition of lipid peroxidation significantly greater than the sum of the individual inhibitions. Our data provide the first evidence that beta carotene can act synergistically with alpha-tocopherol as an effective radical trapping antioxidant in membranes. PMID- 1637181 TI - Modulation of calmodulin levels, calmodulin methylation, and calmodulin binding proteins during carrot cell growth and embryogenesis. AB - Carrot cell cultures were used to study the dynamics of calmodulin protein levels, calmodulin methylation, and calmodulin-binding proteins during plant growth and development. Comparisons of proliferating and nonproliferating wild carrot cells show that, while calmodulin protein levels does not vary significantly, substantial variation in post-translational methylation of calmodulin on lysine-115 is observed. Calmodulin methylation is low during the lag and early exponential stages, but increases substantially as exponential growth proceeds and becomes maximal in the postexponential phase. Unmethylated calmodulin quickly reappears within 12 h of reinoculation of cells into fresh media, suggesting that the process is regulated according to the cell growth state. Calmodulin and calmodulin-binding proteins were also analyzed during the formation and germination of domestic carrot embryos in culture. Neither calmodulin methylation nor calmodulin protein levels varied significantly during somatic embryogenesis. However, upon germination of embryos, the level of calmodulin protein doubled. By calmodulin overlay analysis, we have detected a major 54,000 M(r) calmodulin-binding protein that also increased during embryo germination. This protein was purified from carrot embryo extracts by calmodulin Sepharose chromatography. Overall, the data suggest that calmodulin methylation is regulated depending upon the state of cell growth and that calmodulin and its target proteins are modulated during early plant development. PMID- 1637182 TI - Modification of acidic residues normalizes sodium dodecyl sulfate-polyacrylamide gel electrophoresis of caldesmon and other proteins that migrate anomalously. AB - Caldesmon migrates as a 140-kDa protein during polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS), although its true molecular mass is close to 90 kDa. Since caldesmon's high acidic residue content may be responsible for this anomaly, it was reasoned that modification of these residues, with a loss of negative charge, might restore normal electrophoretic migration. Therefore caldesmon was reacted with 1-ethyl-3-(3 dimethylaminopropyl)carbodiimide in the presence of excess ethanolamine, which results in negatively charged carboxylates being converted to neutral amides without protein cross-linking. The absence of cross-linking was shown by rotary shadow electron microscopy. In accord with expectations, modified caldesmon migrated as a 94-kDa protein when compared to standards, which were much less affected by modification. The anomalous migration of caldesmon might be due to the repulsion of negatively charged SDS by caldesmon's acidic residues. Low binding of SDS to caldesmon is consistent with the fact that SDS, up to 1%, had little or no effect on the secondary structure of caldesmon, as monitored by circular dichroism. However, other mechanisms can also explain these observations. The abnormal migration of tropomyosin and calsequestrin, both of which have a high percentage of acidic amino acids, was also "normalized" by this treatment. Thus this method might have general application for the electrophoresis of proteins which have a high acidic residue content and migrate anomalously. PMID- 1637183 TI - Variability in the G3 domain content of bovine aggrecan from cartilage extracts and chondrocyte cultures. AB - The content of the globular domains G1, G2 and G3 on the core protein of high density (A1D1) aggrecan isolated from newborn and mature bovine cartilage and from cultures of bovine chondrocytes was examined. Quantitation based on the 220 nm absorbance of tryptic marker peptides from each domain isolated by reversed phase HPLC showed that while the content of G1 and G2 was essentially the same for all samples, the content of G3 varied markedly. The molar yield of G3 and G1 marker peptides indicated that approximately 55% of the G1-bearing aggrecan from immature cartilage carried the G3 domain, while for mature cartilage this figure was markedly reduced, at about 35%. Aggrecan prepared from the cell layer matrix of calf chondrocyte cultures had an apparent G3 content similar to newborn cartilage (55%), whereas aggrecan prepared from the medium of these cultures had a markedly higher G3 content, at about 80%. The high content of G3 in cell medium samples compared to cartilage extracts was supported by electron microscopic analysis of A1D1 preparations. The G3 content of the two subpopulations of aggrecan present in mature cartilage and separable by flat bed agarose gel electrophoresis was also determined at about 45% (Band I) and 20% (Band II) respectively. These results are discussed in terms of the likely origin of the marked variability in the G3 domain content of aggrecan. PMID- 1637184 TI - Baculovirus expression and characterization of catalytically active horseradish peroxidase. AB - Studies of horseradish peroxidase (HRP), a prototypical enzyme, have provided much of the information that is available on the mechanisms and functions of hemoprotein peroxidases. HRP itself is widely used in biotechnological applications. Further progress in defining the structure and function of the enzyme, however, requires its expression in a heterologous system. We report here baculovirus-mediated, high yield expression of a synthetic gene for HRP in Spodoptera frugiperda cell culture. Expression of the soluble, glycosylated protein requires the 5'-leader sequence of the native gene. Recombinant horseradish peroxidase reacts with H2O2 to give compound I, II, and III spectra and a guaiacol oxidation activity, identical to those of the native enzyme. The integrity of the recombinant active site is confirmed by NMR spectroscopy and by catalytic reaction with ethylhydrazine to give a stabilized isoporphyrin that decays exclusively to delta-meso-ethylheme. Furthermore, thioanisoles are oxidized by recombinant and native HRP with the same enantiomeric specificity. HRP expressed in a baculovirus system, despite probable differences in glycosylation, is essentially identical to the native enzyme. PMID- 1637185 TI - Site-directed mutagenesis of glutathione S-transferase YaYa: functional studies of histidine, cysteine, and tryptophan mutants. AB - The rat cytosolic glutathione S-transferase Ya subunit contains three histidine residues (at positions 8, 143, and 159), two cysteine residues (at positions 18 and 112), and a single tryptophan residue (at position 21). Histidine, cysteine, and tryptophan have been proposed to be present either near or at the active site of other glutathione S-transferase subunits. The functional role of these amino acids at each of the positions was evaluated by site-directed mutagenesis in which valine or asparagine, alanine, and phenylalanine were substituted for histidine, cysteine, and tryptophan, respectively. Mutant enzymes H8V, H143V, H159N, C112A, and W21F retained either full or better catalytic efficiencies (k(cat)/Km) toward 1-chloro-2,4-dinitrobenzene and glutathione. Lower but significant k(cat)/Km values were observed for H159V and C18A toward 1-chloro-2,4 dinitrobenzene. Some mutants displayed different thermal stabilities and intrinsic fluorescence intensities, but all retained the ability to bind heme. These results indicate that histidine, cysteine, and tryptophan in the glutathione S-transferase Ya subunit are not essential for catalysis nor are they involved in the binding of heme to the YaYa homodimer. PMID- 1637186 TI - The purification and physicochemical characterization of maize (Zea mays L.) isocitrate lyase. AB - A purification scheme is described for the glyoxylate cycle enzyme isocitrate lyase from maize scutella. Purification involves an acetone precipitation and a heat denaturation step, followed by ammonium sulfate precipitation and chromatography on DEAE-cellulose and on blue-Sepharose. The latter step results in the removal of the remaining malate dehydrogenase activity, and of a high molecular mass (62 kDa) but inactive degradation product of isocitrate lyase. Catalase can be completely removed by performing the DEAE-cellulose chromatography in the presence of Triton X-100. Pure isocitrate lyase can be stored without appreciable loss of activity at -70 degrees C in 5 mM triethanolamine buffer containing 6 mM MgCl2, 7 mM 2-mercaptoethanol, and 50% (v/v) glycerol, pH 7.6. Maize isocitrate lyase is a tetrameric protein with a subunit molecular mass of 64 kDa. Purity of the enzyme preparation was demonstrated by polyacrylamide gel electrophoresis in the presence of dodecylsulfate, in acid (pH 3.2) urea and by isoelectric focusing (pI = 5.1). Maize isocitrate lyase is devoid of covalently linked sugar residues. From circular dichroism measurements we estimate that its structure comprises 30% alpha-helical and 15% beta-pleated sheet segments. The enzyme requires Mg2+ ions for activity, and only Mn2+ apparently is able to replace this cation to a certain extent. The kinetics of the isocitrate lyase-catalyzed cleavage reaction were investigated, and the amino acid composition of the maize enzyme was determined. Finally the occurrence of an association between maize isocitrate lyase and catalase was observed. Such a multienzyme complex may be postulated to play a protective role in vivo. PMID- 1637187 TI - The influence of endogenous acyl-acyl carrier protein concentrations on fatty acid compositions of chloroplast glycerolipids. AB - The concentrations of long-chain acyl-acyl carrier proteins (acyl-ACP) occurring during fatty acid synthesis from [1-14C]acetate within chloroplasts isolated from spinach, pea, and amaranthus leaves were manipulated by making minor changes to a basal incubation medium containing sn-glycerol 3-phosphate (G3P). Pools of oleoyl , stearoyl-, and palmitoyl-ACP were compared with those of the corresponding 1 acyl glycerol 3-phosphates to determine how endogenous acyl-ACP concentrations affected the fatty acid compositions of chloroplast glycerolipids. The 1-acyl G3P synthesized by isolated chloroplasts contained more palmitate than would be expected for the precursor of thylakoid phosphatidylglycerol in the different plant species. However, treatments which increased ratios of oleoyl- to palmitoyl ACP by about 50% increased synthesis of sn-1-oleoyl G3P to the extent anticipated from known fatty acid compositions of the different phosphatidylglycerols. Since stearate constituted 70-73% of the acyl-ACP and 48-51% of the 1-acyl-G3P pool of spinach and pea chloroplasts incubated in the presence of cyanide, it is transferred to G3P much more efficiently in situ than would be predicted from competition studies using mixtures of acyl donors and purified acyltransferases. Increasing concentrations of G3P in incubation media from 0.1 to 2 mM had relatively little effect on the amounts and proportions of acyl-ACPs but forced the synthesis of palmitoyl-G3P and, ultimately, disaturated glycerolipid. It is concluded that the chloroplast G3P acyltransferases are primarily responsible for determining the fatty acid compositions of procaryotic glycerolipids in plants, but that acyl-ACP concentrations may play a more important role than would be anticipated from the kinetics of the purified enzyme. However, those kinetics may be quite complex; allosteric effectors may influence the affinities of the enzyme for oleoyl-ACP and for G3P. PMID- 1637188 TI - Endrin-induced increases in hepatic lipid peroxidation, membrane microviscosity, and DNA damage in rats. AB - Endrin is a polyhalogenated cyclic hydrocarbon pesticide which produces hepatic and neurologic toxicity. Previous studies have indicated that endrin induces hepatic lipid peroxidation. In order to further assess the possible role of lipid peroxidation in the toxicity of endrin, the dose- and time-dependent effects of endrin on hepatic lipid peroxidation, membrane microviscosity and DNA damage in rats were examined. Rats were treated with 0, 3.0, 4.5, or 6.0 mg endrin/kg as a single oral dose in corn oil, and the animals were killed 0, 12, 24, 48, or 72 h post-treatment. Dose-dependent increases in hepatic mitochondrial and microsomal lipid peroxidation and microviscosity as well as nuclear DNA single strand breaks were observed as early as 12 h post-treatment. Maximum increases in these three parameters occurred 24 h after endrin administration at all three doses. While the incidence in DNA damage decreased with time after 24 h, the incidence of lipid peroxidation and microviscosity of microsomal and mitochondrial membranes remained relatively constant. Dose- and time-dependent increases in liver and spleen weight/body weight ratios with decreases in thymus weight/body weight ratios were observed. The data indicate that endrin administration induces hepatic lipid peroxidation which may be responsible for the increased membrane microviscosity as a result of membrane damage as well as enhanced DNA damage. PMID- 1637189 TI - Trace element distribution in growing feathers: additional excretion in feather sheaths. AB - The use of feathers is a non-invasive and repeatable method for biomonitoring trace element levels in birds and their ecosystems. Trace element levels were examined in different parts of growing flight feathers from young common terns (Sterna hirundo) to determine distribution of heavy metals and selenium, potential bias from using partially grown feathers, and whether additional heavy metals and selenium are excreted in feather sheaths that are sloughed before feathers are usually sampled. Lead and mercury levels were significantly higher in the distal fully formed portion of the growing feather (with no residual blood supply) compared to the proximal, growing portion of the feather with a residual blood supply, but no significant differences were evident for cadmium and selenium. These results suggest that using partially grown feathers underestimates the amount of lead and mercury in fully formed feathers and that higher levels of lead and mercury are sequestered in feathers than are present in the blood at any one time. Significantly higher concentrations of lead and cadmium, and significantly lower levels of mercury were in the sheath compared to the whole feather blade. These data suggest that birds excrete more lead and cadmium during molt than previously thought. PMID- 1637190 TI - Cadmium and mercury in emergent mayflies (Hexagenia bilineata) from the upper Mississippi River. AB - Burrowing mayflies (Hexagenia bilineata) were analyzed to assess longitudinal patterns in their cadmium and mercury content along the upper Mississippi River. Emergent mayflies (subimagoes and imagoes) were collected in 1988 at 34 sites (25 navigation pools), extending 1260 km from Little Falls, Minnesota, downstream to St. Louis, Missouri. Cadmium concentrations in composite samples of whole mayflies ranged from 7 to 219 ng/g dry weight in females and from less than 7 to 265 ng/g in males. Cadmium concentrations were highest (greater than or equal to 150 ng/g) in samples from Pools 2 and 3 (downstream from the Twin Cities metropolitan area), 15 (near the Quad Cities metropolitan area), and 27 (near the St. Louis metropolitan area). Cadmium concentrations in female mayflies decreased significantly with distance downstream from Pool 2 at river mile 825 to Pool 9 at river mile 648, paralleling spatial trends in the cadmium contamination of sediments in the reach downstream from the Twin Cities metropolitan area, reported in earlier studies; cadmium burdens in mayflies followed a similar spatial trend. Concentrations of mercury were much less variable, ranging from 44 to 102 ng/g dry weight in female mayflies and from 60 to 177 ng/g in males; concentrations and burdens were highest in mayflies collected at Pools 2, 20, 22, 25, and 27. Mercury concentrations in females decreased significantly with distance downstream from Pool 2 at river mile 825 to Pool 5A at river mile 728.5. Concentrations of mercury and cadmium in composite samples of female mayflies were not correlated, indicating dissimilar longitudinal patterns in concentrations of the two metals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637191 TI - Chronic renal effects in three studies of men and women occupationally exposed to cadmium. AB - We measured sensitive indicators of renal damage in three different populations occupationally exposed to cadmium, and examined the degree of variation in damage and the relative sensitivity of different types of indicators. The three studies included (1) men exposed in a cadmium recovery plant, (2) men exposed in a nickel/cadmium battery plant, and (3) women exposed in the latter plant. The indicators of renal damage were urinary proteins in three categories: (1) the high molecular weight enzymes alanine aminopeptidase (AAP) and N-acetyl-beta-D glucosaminidase (NAG), (2) the intermediate molecular weight protein albumin (ALB), and (3) the low molecular weight proteins retinol-binding protein (RBP) and beta 2-microglobulin (B2M). These tests indicate that exposed groups with higher urine cadmium levels had varying degrees of renal damage. All exposed groups showed evidence of renal damage when compared with their respective control groups. A higher percentage of elevated protein levels was noted in the exposed group of Study 1 than in the exposed groups of Studies 2 and 3. In Study 1, the means of all five protein levels and ALB, RBP, and B2M fractional clearances were significantly elevated in the group with higher urine cadmium concentrations when compared with the groups with lower urine cadmium concentrations. Highly significant dose-response relationships for all of the urinary protein tests, including fractional clearances, were found. All of the tests were more sensitive in detecting evidence of subclinical renal damage than serum creatinine, a commonly used indicator of renal function. The order of test sensitivity in men was determined by considering three factors: (1) the magnitude of the correlation coefficient between the test and the urine cadmium concentration in the study with the most advanced damage, (2) the relative cadmium level predicted by the dose-response model at which there is a 10% chance of observing an elevated test value, and (3) the ability of the tests to detect renal effects in the population with less advanced damage. The tests in order of decreasing sensitivity in men are ALB, AAP, NAG, RBP approximately B2M. The women with higher urine cadmium levels in Study 3 had a higher percentage of elevated AAP and NAG values when compared with the control group. PMID- 1637192 TI - Mitotic toxicity, sister chromatid exchange, and rec assay of pesticides. AB - Genotoxicity of 10 pesticides (chlornitrofen, chlomethoxyfen, molinate, thiobencarb, simazine, simetryn, diazinon, iprofenfos, piperofos and oxadiazone) was studied by mitotic toxicity, sister chromatid exchange, and rec assay. The pesticides are detected frequently at high levels in the Yodo River water in Osaka, Japan, which is used for drinking water by thirteen million people. Mitotic toxicity was evaluated by mitotic index (MI) and second mitosis index (SI), using a Chinese hamster cell line V79. SI is the rate of twice divided metaphases in chromosome preparation for sister chromatid exchange. All the pesticides decreased the two indices dose-dependently. MI50 and SI50, the concentrations of pesticides which lowered the indices to 50% of the solvent control, was determined. The MI50 and SI50 of each pesticide were very similar, and the pesticides did not hinder cell division specifically. None of the pesticides induced more sister chromatid exchanges than 1.5 times the solvent control. Chlomethoxyfen and simazine induced sister chromatid exchanges significantly in V79 cells, but the dose dependencies were poor. Simetryn had rec effect and was concluded to have DNA damaging activity. PMID- 1637193 TI - A method for the trace analysis of naptalam (N-1-naphthylphthalamic acid) in water. AB - A method for the trace analysis of naptalam, N-1-naphthylphthalamic acid, in water is presented. Naptalam, a pre-emergent, broad-leaf, and grassy herbicide, is used with soybean, peanut, and vine crops. Tap and well water samples are extracted on a cyclohexyl solid phase extraction cartridge, eluted from the cartridge with methanol, and evaporated to dryness. The sample is esterified with diazoethane, evaporated to dryness, reconstituted with methanol, and converted to the stable N-1-naphthyl phthalimide in the gas chromatograph (GC) injector port for detection and quantitation using a nitrogen-phosphorus detector. Sample injection technique and injector port temperature are critical to high derivatization yields. Confirmation of conversion to N-1-naphthyl phthalimide was made by gas chromatograph/mass spectrometer (GC/MS). Spiking tests at levels of 3 to 100 micrograms/L showed good recovery. PMID- 1637194 TI - An outbreak of a food-related illness resembling boric acid poisoning. AB - An outbreak of an illness suggestive of boric acid poisoning occurred among 51 persons who had eaten lunch at the cafeteria of the United States Agency for International Development in Islamabad, Pakistan, on February 11, 1990. Affected patients had headache and severe myalgias 2 to 4 hours after eating lunch. Fever, nausea and vomiting, red eyes, and photophobia were also reported. Among 25 patients (49%), a sunburn-like inflammation of the skin of the face developed, which subsequently desquamated. One patient required hospitalization for 1 day because of dehydration. Among all patients, the only symptoms remaining 72 hours after the meal were mild headache, fatigue, and peeling skin. Those persons who became ill were more likely to have eaten one particular food item (minestrone soup) for lunch than were those who did not become ill. A similar illness has been described following ingestion of boric acid. However, the results of an analysis of serum samples collected 3 days after the lunch from 24 patients did not show boron above normal background levels. Because of boron's short half life, however, these data do not rule out the possibility that patients may have had higher boron levels at the onset of the illness. PMID- 1637195 TI - Bioassay-directed chemical characterization of genotoxic agents in the dissolved and particulate water phases of the Besos and Llobregat Rivers (Barcelona, Spain). AB - Particulate (greater than 0.22 microns) and dissolved phases of water concentrates (600 mL) of Llobregat and Besos Rivers (Barcelona, Spain), were tested in the Salmonella/microsome assay, tester strains TA98 and TA100. Most of them showed significant mutagenic activity. However, independently of the application of exogenous metabolic activation, the dimethylsulfoxide extracts of the particulate matter exhibited a stronger mutagenic activity than the dissolved phase. This indicated that both rivers are chronically polluted by frameshift and base-pair substitution mutagens and promutagens. In order to investigate their identity, a bioassay-directed column chromatography fractionation of the base neutrals isolated from the dissolved and particulate phases of Besos river water (7 L) was carried out. The mutagenic activity (TA98) was higher in presence of S9 and was recovered in the more polar fractions, where several mutagenic agents were identified by capillary GC-MS in the negative ion chemical ionization mode (NICI). Among them, o-tolidine, nitroquinoline, nitroaniline, dichlorobenzidine and several aromatic quinones were candidates for fraction mutagenicity. PMID- 1637196 TI - Characteristic trend of persistent organochlorine contamination in wildlife from a tropical agricultural watershed, south India. AB - The residue levels of persistent organochlorines, such as HCH (BHC: 1,2,3,4,5,6 hexachlorocyclohexane) isomers, DDT [1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane] compounds, PCBs (polychlorobiphenyls) and HCB (hexachlorobenzene), were measured in wildlife. The wildlife were sampled from terrestrial and aquatic habitats in and around the agricultural watershed of Parangipettai, South India. On the basis of overall concentrations sigma HCH ranked first followed by sigma DDT, sigma PCB and HCB, reflecting the increasing usage of HCH in recent years in India. The residue levels of organochlorines in birds varied according to their feeding habits and showed the following pattern: inland piscivores and scavengers greater than coastal piscivores greater than insectivores greater than omnivores greater than granivores. High levels of HCH and DDT residues were recorded in Pond heron and Cattle egret which feed in the agricultural fields. Comparison of HCH concentrations in fish and birds in the study area to other locations was made to further understand the dynamics of contaminant accumulation in tropical wildlife. Regarding birds, a wide variation in residue levels could be seen among various countries, with tropical regions registering high levels. In contrast, the variation is not prominent in the case of fish. The residue levels in fish measured in the present study were generally comparable to values reported from other locations. This suggests that the bioavailability of contaminants to the aquatic fauna is less due to the smaller flux and shorter residence time of these chemicals in the tropics. PMID- 1637197 TI - A mass spectroscopic method for analysis of AHH-inducing and other polychlorinated biphenyl congeners and selected pesticides in fish. AB - The 209 polychlorinated biphenyl (PCB) congeners exhibit a wide range in toxicity to fish, birds, and mammals. This paper discusses the use of gas chromatography/mass spectrometry negative chemical ionization (GC/MS-NCI) to quantify congeners of highly suspected toxicity such as IUPAC #77 (3,3',4,4' tetrachlorobiphenyl) and #126 (3,3',4,4',5-pentachlorobiphenyl). GC/MS analysis time needed to produce the necessary resolution was reduced to 1 h per sample or standard, allowing an autosampler to inject 12 samples in 24 hours, plus 12 standards/QC samples. Identification and quantification of some 60+ congeners and several selected pesticides and estimation of total PCBs are also possible within the 1 h analysis. For congeners of high chlorination (penta through octa), the method exhibited excellent sensitivity, such that we could not locate a fish which exhibited PCB levels below our calibrated quantitation range. NCI was not as sensitive for mono through tri and for some tetrachlorinated PCB congeners, an exception being PCB #77, for which sensitivity was of the same order as for the more highly chlorinated biphenyls. Long term stability was excellent. Over a 6-mo period, results of replicate analyses for PCB congeners and pesticides in a composited sample of lake trout (Salvelinus namaycush) from Lake Michigan had a relative standard deviation of 12% of the mean. Over the same time period, mean recoveries for samples spiked at concentrations similar to those in Lake Michigan lake trout were 90-102%. Response was linear over a wide range of concentrations for each of the analyzed compounds. This method is now being used for routine analysis of PCB congeners and selected pesticides in our laboratory. PMID- 1637198 TI - Variability in organochlorine analysis in fish: an interlaboratory study and its implications for environmental monitoring and regulatory standards. AB - Samples of muscle, from four types of fish, that had been spiked at 0.25 and 1.0 mg/kg with hexachlorobenzene (HCB), gamma BHC (lindane), technical chlordane, p,p'-DDT, p,p'-DDE and p,p'-DDD were analyzed by eight laboratories. Some laboratories could not reliably detect organochlorine compounds even though they were registered as national testing laboratories. The analytical accuracies of laboratories that were able to reliably detect the spiked compounds were very variable and exceeded acceptable limits. Within-laboratory precision was generally acceptable. There was significant interlaboratory variability among the estimates of percent lipid for each fish type. This variability negated the use of percent lipid for standardization of organochlorine concentrations for comparison between studies. The results highlight the need for standard analytical protocols that are regularly tested by interlaboratory studies. They also indicate that interchangeability of data between studies is limited due to low analytical accuracy. Therefore, comparison of analytical data to absolute environmental and regulatory standards is difficult. The use of "latitudinal confidence ranges" when setting regulatory standards is recommended. PMID- 1637199 TI - Differential sensitivity of Dugesia dorotocephala and Cheumatopsyche pettiti to water acidification: ecological implication for predator-prey interactions. AB - The initial hypothesis that predation pressure should decrease with decreasing pH in aquatic macrobenthic communities if predatory invertebrates are more sensitive to water acidification than prey invertebrates is tested. Short-term toxicity bioassays were conducted in soft water (average value of total hardness 38.0 mg CaCO3/L) to determine the differential sensitivity of the predator, Dugesia dorotocephala (Turbellaria, Tricladida), and the prey, larvae of Cheumatopsyche pettiti (Insecta, Trichoptera), to low pH. Test pH solutions were prepared with sulfuric acid (H2SO4). Test species were also exposed to high concentrations of sulfate ion (95 mg SO4 =/L for D. dorotocephala and 340 mg SO4 =/L for C. pettiti) as sulfate toxicity controls, using potassium sulfate (K2SO4). No mortality was observed during these toxicity controls, indicating that toxic effects generated by low pH were fundamentally due to H+ ions. The 72 and 96-h LC50s (as pH values) and their 95% confidence limits were 4.88 (4.72-5.05) and 5.04 (4.89-5.21) for D. dorotocephala, and 3.25 (3.00-3.51) and 3.48 (3.24-3.73) for C. pettiti. Net-spinning caddis-fly larvae migrated from their retreat nets and protruded their anal papillae before dying. After short-term bioassays, predation-pressure laboratory experiments were performed for 6 days. The cumulative mortality of C. pettiti by predation of D. dorotocephala decreased with decreasing sublethal pH values. The average predation rates at mean pH values of 7.7, 7.7, 6.6, 6.5, 6.2 and 6.0 were 2.5, 2.0, 1.33, 1.17, 0.67 and 0.33 larvae/day, respectively. The major biotic factor affecting predation pressure appears to be the reduction in the physiological activity of triclads at low pH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637200 TI - Inhibition of binding of thyroxin to transthyretin by outdoor and indoor airborne particulate matter and effects on thyroid hormone and vitamin A metabolism in rats. AB - Previous studies have indicated that chemicals, e.g., hydroxylated polychlorinated biphenyls (PCBs) decrease plasma thyroxin levels through interaction with transthyretin. As a consequence, plasma vitamin A and thyroxin are depleted. Both thyroxin and vitamin A are important regulators of normal epithelial differentiation and proliferation and might act in the promotion phase of carcinogenesis. In the present report, extracts of indoor and outdoor airborne particulate matter (APM), originating from different pollution sources, were tested for a possible interaction in vitro and in vivo with thyroxin and vitamin A. Results indicated that all APM extracts significantly interfered with thyroxin binding to transthyretin. In all cases, the more polluted samples inhibited binding more than the corresponding control samples. Exposure of rats to a cigarette smoke extract induced clear changes in plasma thyroxin and triiodothyronin hormone levels. Triiodothyronin levels were reduced most. Effects on plasma vitamin A levels were also found, but these were less clear. In addition a decrease in lung vitamin A levels was found, but this decrease was not statistically significant. Exposure of rats to an outdoor APM extract induced significant changes in plasma triiodothyronin levels. Effects on thyroxin levels were not significant, although the same trend was seen as for the cigarette smoke APM extract. No changes in plasma or liver vitamin A concentrations were induced by the outdoor APM extract. Lung vitamin A levels were decreased, but again this decrease was not statistically significant. Taken together, the present report shows that APM extracts have the potency to interfere with thyroid hormone metabolism both in vitro and in vivo and probably with vitamin A metabolism as well.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637201 TI - The effect of environmental pH on sodium balance in the red-spotted newt, Notophthalmus viridescens. AB - Sodium influx and efflux of the red-spotted newt, Notophthalmus viridescens, at two pHs were investigated in efts and adults in water and on land. The sodium efflux rate constant was not affected by pH. Efflux was generally greater under aquatic than terrestrial conditions, and for efts than for adults. In an aquatic setting, both adults and efts were able to maintain sodium balance at pH 5, but exhibited net sodium loss at pH 3. Sodium influx was greater in efts at pH 5 than in any other group. Adults in all treatments lost mass during the experiment, while efts in all treatments were able to maintain body mass. In their normal terrestrial environment, red efts probably avoid substantial sodium fluxes by maintaining a hydrophobic skin, which decreases contact with soil solutions. PMID- 1637202 TI - Laundering as decontamination of apparel fabrics: residues of pesticides from six chemical classes. AB - Research on reducing the level of pesticide residue on a textile substrate has examined many variables under many different conditions. This study controlled fiber type and the use of prewash product in an examination of residue levels for a number of pesticides in different pesticide classes. For all pesticides examined, the use of prewash lowered pesticide residues regardless of fiber type. Differences in pesticide residue level attributable to fiber type were not consistent. PMID- 1637203 TI - Acute toxicity, percutaneous absorption and effects on hepatic mixed function oxidase activities of 2,4,4'-trichloro-2'-hydroxydiphenyl ether (Irgasan DP300) and its chlorinated derivatives. AB - Acute toxicity of 2,4,4'-trichloro-2'-hydroxydiphenyl ether (Irgasan DP300) (I) and its three chlorinated derivatives, 2',3,4,4'-tetrachloro-2-hydroxydiphenyl ether (II), 2',4,4',5-tetrachloro-2-hydroxydiphenyl ether (III) and 2',3,4,4',5 pentachloro-2-hydroxydiphenyl ether (IV), in mice were examined by intraperitoneal injection. The LD50 values of Irgasan DP300, II, III and IV were 1,090, 710, 650 and 430 mg/kg, respectively. The percutaneous absorptions of these tritiated compounds were also examined by the application on the backs of mice. The radioactivities in most tissues reached to the maximal levels at 12 h or 18 h after dosing, which corresponded to 11-76% of the maximal levels given by the oral administration (Kanetoshi et al. 1988a). These results show the high percutaneous absorbability of Irgasan DP300 and its chlorinated derivatives. The intraperitoneal administrations of III and IV to rats induced hepatic microsomal aminopyrine N-demethylase and aniline 4-hydroxylase activities similarly to phenobarbital. These chlorinated derivatives also increased cytochrome P-450 content, and the activities of aminopyrine N-demethylase and N-methylaniline N demethylase in hepatic microsomes from mice. The extents of the increases were similar to those by phenobarbital and 3-methylcholanthrene. PMID- 1637204 TI - Serum esterase inhibition in birds: a nondestructive biomarker to assess organophosphorus and carbamate contamination. AB - With the aim of proposing a nondestructive biomarker for monitoring the toxicological risk to birds of exposure to the organophosphorus insecticide azamethiphos and the carbamate insecticide methomyl, laboratory studies were performed on serum "B" esterases in Japanese quail (Coturnix coturnix japonica). The birds received two single dose treatments of each compound (azamethiphos and methomyl), i.e., 50 mg/kg and 250 mg/kg respectively. In the first treatment, serum butyrylcholinesterase (BChE) and carboxylesterase (CbE) were drastically inhibited in the azamethiphos-treated group, 24 h after the dose. No inhibition was detected for BChE and CbE activities in the methomyl-treated group, 24 h after the dose. In the second treatment, the birds died or were sacrificed 3 h after the dose. Serum BChE and brain acetylcholinesterase (AChE) were strongly inhibited after treatment with both insecticides. Serum CbE, hepatic microsomal CbE and 7-ethoxyresorufin dealkylation activities were also inhibited. A statistically significant correlation between serum BChE and brain AChE was found at lethal and sublethal doses of these xenobiotics. The experimental results indicate that the nondestructive biomarker BChE can give an early qualitative and semi-quantitative warning of the toxic effects of organophosphate and carbamate insecticides in birds. PMID- 1637205 TI - Herbert Sloan Lecture. The international cardiothoracic surgeon. PMID- 1637206 TI - Barrett's esophagus with high-grade dysplasia: an indication for esophagectomy? AB - Between 1982 and 1991, 19 patients (17 men and 2 women) with Barrett's esophagus, 10 of whom were in a surveillance program, were found to have high-grade dysplasia without evidence of invasive carcinoma. Median age was 66 years (range, 30 to 79 years). Heartburn was the most common presenting symptom. Esophagoscopy at the time of high-grade dysplasia diagnosis demonstrated normal Barrett's mucosa in 10 patients (53%), shallow ulcers in 3, slight mucosal irregularities in 2, small mucosal nodules in 2, stricture in 1, and shallow ulcer with stricture in 1. Eighteen patients underwent esophagectomy. There were no operative deaths. Nine patients (50%) had invasive carcinoma. Postsurgical stage was stage 0 in 9 patients, stage I in 6, stage IIA in 2, and stage IIB in 1. Median follow-up was 34 months (range, 2 to 116 months). Recurrent cancer developed in 2 patients. Overall 5-year survival was 66.7%; 5-year survival for patients with stage 0 disease was 100% and for stage I and II disease, 35.7%. We conclude that high-grade dysplasia in an indication for esophageal resection because of the high rate of associated early invasive carcinoma and that resection can be done safely with the expectation of excellent long-term survival. Because of these findings, we continue to recommend endoscopic surveillance in all patients with Barrett's esophagus. PMID- 1637207 TI - Treatment of AIDS-related bronchopleural fistula by pleurectomy. AB - Spontaneous pneumothorax in patients with acquired immunodeficiency syndrome (AIDS) may require prolonged therapy for treatment of a persistent bronchopleural fistula, and treatment by standard methods often fails. This pilot study was done to test the effectiveness of aggressive surgical therapy for definitive treatment of persistent bronchopleural fistula in patients with AIDS. Between March 1989 and September 1991, 44 patients with AIDS were treated for spontaneous pneumothorax with closed tube thoracostomy; 14 of these patients had development of persistent bronchopleural fistula for more than 10 days, and 2 patients had subsequent bronchopleural fistula on the opposite side. Operative therapy in 14 patients included 15 thoracotomies and one sternotomy. The bronchopleural fistula was closed directly with suture or staples in 15 procedures and resected by lobectomy in 1 patient. All 14 patients received adjuvant parietal pleurectomy. Operative mortality was 7% (1 of 14 patients). The fistula was closed in all survivors and 13 patients were discharged between 7 and 28 days postoperatively. Pathologic examination confirmed Pneumocystis carinii in 13 patients with a high incidence of diffuse involvement and subpleural necrosis, further demonstrating the need for pleurectomy. These data suggest that in selected patients bronchopleural fistulas associated with AIDS can be effectively controlled by surgical closure combined with pleurectomy. PMID- 1637208 TI - Pediatric lung transplantation for pulmonary hypertension and congenital heart disease. AB - Five children underwent lung transplantation for end-stage pulmonary hypertension and respiratory insufficiency associated with congenital heart disease. One (17 mo) had pulmonary hypertension with a patent ductus arteriosus and required two periods of preoperative extracorporeal membrane oxygenation before successful bilateral sequential lung transplantation. One (21 mo) required bilateral lung transplantation for pulmonary hypertension and bronchopulmonary dysplasia associated with iatrogenic injury to the left pulmonary artery. This child also had patent ductus arteriosus ligation and preoperative catheter closure of an atrial septal defect. Extracorporeal membrane oxygenation was required for early postoperative pulmonary support. One child underwent right single-lung transplantation and closure of an atrial septal defect for pulmonary hypertension. Two patients had single-lung transplantation for Eisenmenger's syndrome: 1 with muscular inlet ventricular septal defect closure, atrial septal defect closure, and right single-lung transplantation; 1 with ventricular septal defect closure, patent ductus arteriosus ligation, right ventricular outflow tract patch repair, and single-lung transplantation. All patients survived operation, with one late death (lymphoproliferative disease). The 4 survivors are all ambulatory without oxygen and have evidence of normal pulmonary artery pressure 9 to 12 months after transplantation. PMID- 1637209 TI - Primary bony and cartilaginous sarcomas of chest wall: results of therapy. AB - Primary bony and cartilaginous sarcomas of the chest wall are uncommon, and data concerning treatment and results are sparse. To assess the results of therapy, we reviewed our 40-year experience. Records of 38 patients with osteosarcoma and 88 with chondrosarcoma arising in chest wall admitted to Memorial Sloan-Kettering Cancer Center from 1949 to 1989 were reviewed. The 88 patients with chondrosarcoma ranged in age from 5 to 86 years (median age, 49 years); the male/female ratio was 1.3:1. Presenting complaint was mass, pain, or both in 93%. Primary therapy was resection (n = 84), radiation therapy (n = 3), or chemotherapy (n = 1). Overall 5-year survival was 64%. Significant adverse prognostic factors included metastases at initial presentation (n = 9), metastases at any time during the course of disease (n = 23), age greater than 50 years (n = 42), incomplete or no resection (n = 13), and local recurrence (n = 24). Sex, grade, and tumor size were not prognostic factors. The 38 patients with osteosarcoma ranged in age from 11 to 78 years (median age, 42 years); the male/female ratio was 1.5:1. Presenting complaint was mass, pain, or both in 95%. Primary therapy included resection (n = 31; alone in 13, with radiation therapy in 3, with chemotherapy in 15), radiation therapy (n = 3), radiation therapy and chemotherapy (n = 2), chemotherapy (n = 1), or no treatment (n = 1). Overall 5 year survival was 15%. Significant adverse prognostic factors included presence of synchronous metastases (n = 13) and metastases at any time during the course of disease (n = 26).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637210 TI - Prolonged open sternotomy and delayed sternal closure after cardiac operations. AB - Maintenance of an open sternotomy (OS) after a complicated cardiac operation is an adjunct in the treatment of the severely impaired heart. We hypothesized that predictors of the timing, morbidity, and prognosis of delayed sternal closure (DSC) could be determined by intensive case review. Prolonged OS was used in 107 of 6,030 adult open heart patients (1.8%) between 1987 and 1991. Indications for OS were hemodynamic instability (40), myocardial edema (18), intractable bleeding (23), relentless arrhythmias (9), and ventricular assist devices (17). Delayed sternal closure was carried out in 75 of 107 patients at a mean of 3.4 +/- 0.3 days after OS. Fifty of these 75 (67%) survived and were discharged an average of 43 +/- 6 days after closure. Fifty-seven patients died: 32 before DSC at 3.7 +/- 0.8 days after OS and 25 after DSC at 27 +/- 4 days after OS. Baseline cardiac index (1.7 +/- 0.1 L.min-1.m-2) improved an average of 1.0 +/- 0.1 L.min-1.m-2 after OS (p less than or equal to 0.001) and remained stable through DSC (2.5 +/- 0.3 L.min-1.m-2) and late (9 +/- 0.7 days) follow-up (2.8 +/- 0.1 L.min-1.m-2). Delayed sternal closure in patients without ventricular assist devices was significantly more likely to be successful (45/63 versus 9/27; p less than 0.002) when carried out after the onset of a negative daily fluid balance. Sternal infection occurred in 4 of 75 (5%) patients after DSC and was associated with bleeding as an indication for OS (3/15 versus 1/60; p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637211 TI - A staged expanding pulmonary artery band. AB - Pulmonary artery banding is indicated in numerous congenital cardiac defects not amenable to a total repair. One complication of pulmonary artery banding, especially in neonates who require early banding, is progressive cyanosis during the rapid growth phase requiring earlier than anticipated total correction, which may produce a less than optimal result. A simple pulmonary artery band that enlarges as the patient grows would avoid this early complication. We report a technique of pulmonary artery banding in an animal model using different absorbable sutures. The band enlarges in a prescribed staged fashion without any further intervention, hopefully allowing growth of neonates and infants with complex congenital heart disease. PMID- 1637212 TI - Long-term survival after resection of pulmonary metastases from carcinoma of the breast. AB - Resection of isolated pulmonary metastases may yield improved survival in select patients. Between 1981 and 1991, 44 women (median age, 55 years) with a history of breast cancer underwent 47 thoracotomies with no operative deaths and only three minor postoperative complications (3/47, 6.4%). Confirmation of the metastatic origin of the lung lesion was made by direct histological comparison with the primary. Three patients had benign nodules and were excluded, and 4 patients had less than complete resection at thoracotomy. The median survival after thoracotomy of the remaining 37 patients with completely resected metastases was 47 +/- 5.5 months, and their actuarial 5-year survival was 49.5%. Patients with a disease-free interval of longer than 12 months had a longer survival (median survival, 82 +/- 6 months; 5-year survival, 57%) than patients with a disease-free interval of 12 months or less (median survival, 15 +/- 3.6 months; 5-year survival, 0%) (p = 0.004). Patients with estrogen receptor positive status (n = 14) tended to have longer survival after resection than patients with estrogen receptor-negative status (n = 15) (median survival, 81 +/- 9 months versus 23 +/- 6 months, respectively; p = 0.098). Other clinical variables analyzed did not predict survival after thoracotomy. We conclude that resection of pulmonary metastases in patients with breast cancer can be done safely and may result in long-term survival for a substantial number of patients. Patients with a disease-free interval of longer than 12 months have an excellent prognosis after complete resection. PMID- 1637213 TI - Thallium imaging in preoperative evaluation of the pulmonary resection candidate. AB - The major determinants of morbidity and mortality after pulmonary resection are the physiologic status of the cardiac and pulmonary systems. The role of thallium 201 imaging was reviewed in 151 consecutive patients to determine its significance in physiologic assessment. 10.3% of patients were found to have serious asymptomatic coronary artery disease, and thallium imaging made a difference in the management of 50% of these patients. When used appropriately, thallium imaging is an important modality in physiologic assessment of the pulmonary resection candidate. PMID- 1637214 TI - Hypothermic thoracic and thoracoabdominal aneurysm operation: a central cannulation technique. AB - Surgical resection of the descending thoracic and thoracoabdominal aorta is associated with the risk of spinal cord ischemic injury, particularly in patients with aortic dissection. Hypothermic total cardiopulmonary bypass with periods of circulatory arrest has been advocated for spinal cord protection with encouraging early results. However, techniques for this procedure are relatively complex. An alternative cannulation technique with venous return from the right atrium through the internal jugular vein and arterial return to the aortic arch is described. This has been used in 6 patients for replacement of the descending thoracic or thoracoabdominal aorta. Despite profound hypothermia and preservation of the principal spinal radicular artery, 1 patient suffered early paraparesis with some recovery but eventually died of multisystem failure. A second elderly patient with severe obstructive airways disease died of respiratory failure 11 days postoperatively. Four patients made a good recovery including 1 with a ruptured thoracoabdominal aneurysm who subsequently required gut resection for ischemic necrosis present preoperatively. This cannulation technique together with profound hypothermia has greatly improved the operating conditions for extensive aneurysms of the thoracoabdominal aorta. Paraparesis occurring despite hypothermic protection and attempted preservation of the spinal cord arterial supply suggests that unfavorable vascular anatomy still predominates in the risk factors for ischemic injury. PMID- 1637215 TI - Glucose and insulin supply before cardiopulmonary bypass in cardiac surgery: a double-blind study. AB - A double-blind study versus placebo was carried out to evaluate the effects of a 500-mL infusion of 30% glucose containing 300 units of ordinary insulin and 5 g of potassium chloride administered at a rate of 1.66 mL.kg-1.h-1 for 1 hour before cardiopulmonary bypass. The hemodynamic parameters measured before and after administration of the solution, after cardiopulmonary bypass, after administration of protamine, and 3 hours after leaving the operating room showed the beneficial effect of the glucose-insulin-potassium infusion on cardiac index (+23.6% after protamine infusion) and left (+16.3% 3 hours postoperatively) and right (+47.3% after cardiopulmonary bypass) ventricular workload index with a decrease in systemic vascular resistance. For patients with a cardiac index of less than 2.5 L.min-1.m-2 before administration of the glucose-insulin-potassium solution, the beneficial effect on the cardiac index was further increased 3 hours postoperatively (+33%). During the postoperative period, the requirements in inotropic drugs and disturbances of rhythm were not significantly different between the two groups, although they were twofold lower in patients receiving glucose-insulin-potassium. Laboratory tests showed that postoperative hypoglycemia was more common in the glucose-insulin-potassium group but had no detrimental effects; it no longer occurs since we began administering the glucose infusion at 15 g/h over 8 hours. The data reflect the beneficial effect associated with the action of glucose-insulin-potassium on myocardial protection during heart operations and were confirmed by the hemodynamic results. This argues in favor of the routine use of this technique, especially in patients with poor ventricular function. PMID- 1637216 TI - Morphology of the posterior junctional area in atrioventricular septal defects. AB - The location and size of the coronary sinus in hearts with atrioventricular septal defect were investigated in relation to the known disposition of the atrioventricular conduction axis. We examined the morphology in 40 hearts and supplemented this series with two other hearts that had been serially sectioned previously. The coronary sinus received drainage from a persistent left superior caval vein in 5 hearts. Six cases of 40 had malalignment of the septal structures relative to the crux of the heart. In these, the conduction axis was anticipated to course in the position where the inlet ventricular septum met the atrioventricular junction. The coronary sinus terminated in the left atrium in 4 hearts: 2 in the morphological series and 2 that were sectioned for histological studies. The sectioned hearts showed the atrioventricular conduction axis in the usual position for the defect, unrelated to the coronary sinus. The principle that the node and penetrating bundle are located at the intersection of the ventricular septum with the atrioventricular junction holds good despite the variability of the coronary sinus. PMID- 1637217 TI - Long-term follow-up results after reconstruction of the mitral valve by leaflet advancement. AB - In this study, we discuss the clinical results of mitral leaflet advancement performed on 29 patients over the past 10 years and attempt to determine the indication. Preoperative diagnosis of mitral valve lesion consisted of mitral regurgitation in 21 patients and mitral stenosis in 8 patients. Mitral valve repair was applied to the anterior mitral leaflet in 2, the posterior mitral leaflet in 25, and bilateral leaflets in 2 patients. Reoperation was performed on 13 patients, and 1 patient died of renal failure immediately after reoperation. No reoperation was needed for 96.6% of the patients at 1 year, 89.5% at 5 years, 75.0% at 8 years, 63.8% at 10 years, and 52.6% at 15 years postoperatively. At reoperation, the repaired mitral leaflet was found to be calcified in 3 patients more than 9 years after the initial operation. Of the 12 survivors without reoperation, mitral stenosis associated with regurgitation was obvious in 6 patients. Of the 21 patients with preoperative mitral regurgitation, 90.0% showed no deterioration at 5 years, 79.7% at 8 years, and 69.1% at 10 years. On the other hand, for the 8 patients with mitral stenosis, the rates were 87.5% at 1 year, 62.5% at 5 years, 50.0% at 8 years, and 25% at 10 years. Our results suggest that mitral leaflet advancement shows satisfactory results in patients with mitral regurgitation but is not successful for patients with mitral stenosis in the long term because the repaired valve tends to be stenotic in the late postoperative period. PMID- 1637218 TI - Successful treatment of postoperative chylothorax using an external pleuroperitoneal shunt. AB - We report 3 patients with chylothorax who were successfully managed as outpatients using external pleuroperitoneal shunts. This external shunt has the advantage over subcutaneously placed shunts of pumping large volumes of fluid with each compression of the pumping chamber, of not causing the discomfort associated with pumping a subcutaneous chamber, of not becoming difficult to find in the subcutaneous space, and of being constructed of larger components which do not kink or become easily clogged with fibrinous debris. PMID- 1637219 TI - Thoracic aortic operations in patients aged 70 years or older. AB - Thirty-one patients over the age of 70 years (group A) and 72 patients less than 69 years (group B) underwent a variety of thoracic aortic surgical procedures. Early and long-term results and cerebral function were compared between the two groups. Preoperative and postoperative cerebral function was evaluated using mini mental state-Himeji and Wechsler adult intelligence scale tests. The operative mortality of groups A and B was 12.9% and 11.1%, respectively (not significant). There were no significant differences in postoperative complications between the two groups. The late mortality rates of groups A and B were 11.1% and 9.3%, respectively (not significant). There were no significant differences between the two groups in the mini mental state-Himeji test, digit symbol, vocabulary, and total Wechsler adult intelligence scale scores before and after operation. We conclude that thoracic aortic surgical procedures in patients over 70 years of age can be performed with acceptable mortality and morbidity risks. Most patients showed symptomatic improvement. PMID- 1637220 TI - Long-term results of the Ivalon baffle mitral valve repair. AB - In the evolution of mitral valve surgery, Ivalon sponge was sutured to the posterior leaflet of the mitral valve to obtain competency. Between August 1959 and October 1962, 18 patients had this procedure. All patients were discharged home. Three patients were lost to follow-up 5 to 10 years after operation. Valve replacement was necessary in 7 patients 10.4 +/- 8.5 years after repair. Bacterial endocarditis causing late death occurred in 5 patients within 4 years. Five embolic episodes occurred. The estimated probability of survival and need for valve replacement at 28 years were 29.2% +/- 12.3% and 12.4% +/- 6.7%, respectively. PMID- 1637221 TI - Pulmonary torsion: a questionnaire survey and a survey of the literature. AB - Pulmonary torsion is a rare but life-threatening complication of thoracic operations and trauma. A questionnaire was sent to 140 thoracic surgeons in the United Kingdom to examine its incidence, particularly torsion of the middle lobe after right upper lobectomy. The answers from 117 thoracic surgeons (84%) were collected and analyzed. Thirty-five responders (30%) had seen one or more cases of pulmonary torsion. The majority of cases occurred after pulmonary resection, and most of these instances involved middle lobe torsion after right upper lobectomy. In total, 39 cases were reported; 1 (3%) occurred spontaneously in an azygos lobe, 2 (5%) were seen after trauma, 28 (72%) were seen after pulmonary resections and 8 (21%), after other procedures. In this group of responders, 27 (77%) routinely fix the middle lobe to the remaining lobe after right upper or lower lobectomy, upper lobe fixation being required only if the transverse fissure is well developed. Of the 82 responders who had never seen instances of pulmonary torsion, only 47 (57%) routinely do this fixation. PMID- 1637222 TI - Concomitant cardiac and pulmonary operation: the role of cardiopulmonary bypass. AB - To assess the safety and efficacy of concomitant pulmonary resection and cardiac operation requiring cardiopulmonary bypass, the records of 19 patients were reviewed. Eighteen patients (94.7%) presented with cardiac symptoms and were found to have pulmonary pathology of indeterminate etiology. Pulmonary resections were performed through a median sternotomy in all but 1 patient, who underwent posterolateral thoracotomy and right middle lobectomy after repositioning because dense adhesions prevented adequate dissection through the initial incision. A total of 24 resections were performed. Sixteen (66.7%) were performed on cardiopulmonary bypass. Six wedge resections (25.0%) were performed before bypass. Two lobectomies (8.3%) were performed after infusion of protamine sulfate. Nine patients (47.4%) had benign pathology, 7 (36.8%) had primary carcinoma, and 3 (15.8%) had metastatic disease. Bleeding complications occurred in 15.8% of patients (3/19). There was 1 perioperative death (5.3%), which was due to adult respiratory distress syndrome after intraoperative hemorrhage followed lobectomy for bullous disease. Another patient required lateral extension of the sternotomy during an episode of exsanguinating intraparenchymal pulmonary hemorrhage, which resulted in lobectomy, as well as costochondral and sternal osteomyelitis. A third patient required exploration for bleeding at the staple line. Postoperative complications occurred in 7 patients (36.8%) and were predominantly respiratory (5/7, 71.4%) (p = 0.006). The median postoperative hospitalization was 15 days. Although comparison of patients who underwent pulmonary resection during bypass with those who had resection either before heparinization or after protamine infusion showed no significant difference with respect to age, incidence of malignancy, operation performed, complications, postoperative hospitalization, or survival, this was probably due to the small number of patients in the study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637223 TI - Open lung biopsy for diffuse infiltrative lung disease. AB - The purpose of this study was to determine the most appropriate site of biopsy in patients with diffuse infiltrative lung disease (DILD). Twenty patients were evaluated. During open lung biopsy, a representative region (inflamed and least fibrotic) of the radiographically most involved lobe was identified and a biopsy done. A second biopsy specimen was obtained from an adjacent accessible lobe. The biopsy specimen from each lobe was processed separately, and a descriptive histologic report was generated for each of the two lobes. Tissue was cultured for bacteria, fungi, and mycobacteria. In 17 patients, the second biopsy site had fewer roentgenographic abnormalities than the radiographically most involved lobe. In 3 patients, the number of radiographic abnormalities was equal in all lobes. The same pathologic diagnosis was reached by histologic examination of the two biopsy specimens in 8 of 10 patients with acute DILD and in 10 of 10 patients with chronic DILD. In 2 patients, the biopsy specimen from the radiographically most involved lobe showed pathologic features not seen in the other specimen. Cultures from both biopsy specimens were grown separately in 6 patients. Fungi (n = 2) and bacteria (n = 1) were isolated from the radiographically most involved lobe (n = 2) or from the lobe of initial lung infiltration (n = 1) in 3 patients. When biopsy specimens are obtained from a representative region of the radiographically most involved lobe in patients with DILD, biopsy of other lobes is unnecessary. PMID- 1637224 TI - Acute severe postischemic myocardial depression reversed by triiodothyronine. AB - The purpose of this study was to determine the effects of triiodothyronine (T3) on postischemic left ventricular performance and high-energy phosphate content in a severe injury model. Isolated working rat hearts (n = 63) received 20 mL of hyperkalemic NIH No. 1 cardioplegia and were subjected to 20 minutes of ischemia at 37 degrees C. Treated hearts were reperfused with T3-supplemented modified Krebs-Henseleit buffer. Control hearts did not receive T3 supplementation. All treated hearts (n = 44) performed work after ischemia, whereas 26% (5/19) of the control hearts were not able to perform any left ventricular work after ischemia. Comparisons with preischemic values demonstrated significant progressive hemodynamic recovery with increasing concentrations of T3 (0, 0.06, 0.15, and 0.60 ng/mL) with concomitant recovery of left ventricular stroke work index (63%, 72%, 89% [p less than 0.05], and 99% [p less than 0.05], respectively). There were corresponding increases in recovery of aortic flow, systolic pressure, cardiac index, and stroke volume index (p less than 0.05). There were no significant changes in coronary sinus flow or heart rate in any group compared with preischemic values. Comparisons of postischemic high-energy phosphate concentrations also demonstrated no change between treated and untreated groups (p greater than 0.05). We conclude that administration of T3 in a severe left ventricular injury model significantly augments rapid ventricular recovery with no change in postischemic high-energy phosphate concentrations. PMID- 1637225 TI - Accessory atrioventricular node and bundle: a cause of antidromic reentry tachycardia. AB - Two patients are described with antidromic reentry tachycardia successfully treated by interruption of an anterior septal accessory atrioventricular node and bundle. This anomalous connection resembles an atrioventricular conduction sling seen in complex congenital heart malformations. It has atrioventricular node-like properties, is located in the anterior septal area, will only conduct antegrade, and has an insulated connection to the right bundle branch. Rather than nodoventricular, nodofascicular, atriofascicular, or Mahaim, a more appropriate label for the connection is accessory atrioventricular node and bundle. PMID- 1637226 TI - Adjuvant radiotherapy after complete resection of thymoma. AB - Seventy patients were studied after undergoing complete resection of thymoma to determine the effect of postoperative adjuvant mediastinal radiotherapy on prognosis, with regard to clinical stage, histological type, and pleural factor. Pleural factor was defined as follows: p0, no adhesion to the mediastinal pleura; p1, fibrous adhesion to the mediastinal pleura without microscopic invasion; and p2, microscopic invasion of the mediastinal pleura. Recurrence of thymoma after complete resection was observed in 13 patients, 12 (92%) with pleural dissemination, 6 (46%) with local recurrence, and 2 (15%) with distant metastasis (types of recurrence are overlapping). In stage I and stage II p0 patients, no recurrence was observed, regardless of mediastinal radiotherapy. Whereas mediastinal irradiation completely prevented recurrence in stage II p1 patients, 4 (36.4%) nonirradiated stage II p1 patients experienced recurrence. In stage II p2 patients, 75% had pleural dissemination even after radiotherapy. A high incidence of recurrence was also observed in stage III, nonirradiated (25%) and irradiated (30%) patients. The results suggest that mediastinal irradiation for stage I and II p0 patients is not always necessary, and that therapy for stage II p1 is essential and also expected to decrease the recurrence rate. On the other hand, in stage II p2 and stage III thymomas, mediastinal irradiation is not sufficient to prevent pleural recurrence even after complete resection. Our classification based on pleural factor is useful for better selection of appropriate postoperative treatment for thymoma patients. PMID- 1637227 TI - Skeletal muscle ventricles as left atrial-aortic pumps: short-term studies. AB - In 5 dogs, skeletal muscle ventricles (SMVs) were constructed from the latissimus dorsi muscle and placed in the left hemithorax. After a 3-week vascular delay period, SMVs were electrically preconditioned with 2-Hz stimulation for 6 weeks. At a second operation, SMVs were connected between the left atrium and thoracic aorta by afferent and efferent aortic root homografts, and stimulated to contract in a 1:2 diastolic mode. At a mean left atrial pressure of 12.4 +/- 1.3 mm Hg and a burst stimulation frequency of 33 Hz, SMV stroke volume was initially 43% of that of the native left ventricle, achieving a flow equivalent to 21% of cardiac output (194 +/- 38 versus 902 +/- 85 mL/min). At 50-Hz stimulation, this figure rose to 27% (246 +/- 41 mL/min; p less than 0.05). Skeletal muscle ventricle power output (the product of stroke work and contraction rate) at 33 Hz was 0.016 +/- 0.003 W, increasing to 0.024 +/- 0.004 W at 50 Hz (p less than 0.05), corresponding to 14% and 22%, respectively, of left ventricular power output (0.11 +/- 0.012 W). After 4 hours of continuous pumping, four of the SMVs were still generating flows of more than 70% of starting values and more than 60% of initial power output. This study demonstrates that SMVs can function in the systemic circulation at physiologic left atrial preloads. PMID- 1637228 TI - Isolated extracardiac unruptured sinus of Valsalva aneurysms. AB - Reports concerning unruptured, isolated aneurysms of one sinus of Valsalva are rare. These aneurysms usually protrude inside the heart and are very rarely extracardiac. We report 4 cases of isolated, unruptured extracardiac aneurysms of the noncoronary sinus of Valsalva. Clinical symptoms were nonspecific. Operation was performed by patch reconstruction of the dilated aortic sinus without replacement of the ascending aorta. Microscopic examination of the diseased aortic wall revealed absence of medial elastic fibers. Late follow-up in all 4 cases revealed a normal ascending aorta with no dilatation of the aortic root and no aortic regurgitation. PMID- 1637229 TI - Heterotopic heart transplantation and recipient heart operation in ischemic heart disease. AB - The role of heterotopic heart transplantation in coronary heart disease has not been defined. Between 1983 and 1988, 28 patients with end-stage ischemic heart disease were managed by heterotopic heart transplantation and adjunctive operation on the recipient heart: coronary artery bypass grafts and aneurysmectomy, 20; coronary artery bypass grafts, 5; and aneurysmectomy, 3. Indications were feasibility of operative procedures to the recipient heart and small donor size (61% of the donors were less than 15 years). The 1-year and 5 year actuarial survival was 79% and 63%. Of the 22 patients who survived to 2 year follow-up, all of whom had been severely limited (New York Heart Association grade III/IV) preoperatively, 20 were in grades I or II at 2-year follow-up (p less than 0.001). In 14 of 22 patients (64%), the recipient heart augmented the donor cardiac output substantially, and in 4 the recipient heart supported the patient when the donor heart failed to eject. In conclusion, this series demonstrates the efficacy of heterotopic transplantation combined with operation to the recipient heart in the management of patients with end-stage ischemic heart disease. PMID- 1637230 TI - Surgical treatment for ectopic atrial tachycardia. AB - Atrial tachycardia is an infrequent but potentially dangerous arrhythmia which often determines cardiac enlargement. Surgical ablation of the arrhythmia is effective and safe, provided a careful atrial mapping is performed and the surgical technique is tailored to the individual focus location. Eight patients underwent surgical ablation of ectopic atrial tachycardia between 1977 and 1990. Different techniques were adopted for each patient according to the anatomical location of the focus and possibly associated arrhythmias. Whenever possible, a closed heart procedure was chosen. In 1 patient a double focal origin was found and treated by separate procedures. In 1 patient with ostium secundum atrial septal defect and atrial flutter, surgical isolation of the right appendage and the ectopic focus was performed. In all patients ectopic atrial tachycardia was ablated with maintenance of the sinoatrial and atrioventricular nodal function as well as internodal conduction. In follow-up up to December 1991, no recurrency was recorded. PMID- 1637231 TI - Optimal level of hypothermia for prolonged myocardial protection assessed by 31P nuclear magnetic resonance. AB - The optimal level of hypothermia during myocardial preservation for cardiac transplantation is not known. Phosphorus 31 nuclear magnetic resonance spectroscopy was used to assess the effect of different preservation temperatures (15 degrees C in group 1, 4 degrees C in group 2) on the myocardial high-energy phosphate profiles during prolonged global ischemia and subsequent reperfusion of isolated rat hearts. Adenosine triphosphate depletion during ischemia was more gradual in group 2, leading to significant differences in myocardial adenosine triphosphate concentrations between the two groups after 3 hours of ischemia. The fall in intracellular pH during ischemia was significantly less pronounced in hearts preserved at 4 degrees C as compared with those at 15 degrees C. The postischemic recovery of both the left ventricular peak systolic pressure and the maximum rate of increase of left ventricular pressure was enhanced in group 2, although the ischemic period was 3 hours longer than in group 1. Hypothermia at 4 degrees C as compared with 15 degrees C appears to prolong myocardial protection with respect to adenosine triphosphate preservation, prevention of the fall in intracellular pH, and the enhancement of postischemic hemodynamic recovery. PMID- 1637232 TI - Tricuspid valve obstruction caused by plasmacytoma metastasis. AB - A patient undergoing resection of a solid, right-sided intracardiac plasmacytoma metastasis causing severe dyspnea and tricuspid valve obstruction is reported. A review of the literature verified the rarity of this clinical finding. PMID- 1637233 TI - Bilateral adrenal hemorrhage after an open heart operation. AB - Bilateral adrenal hemorrhage and acute adrenal insufficiency were diagnosed after coronary bypass grafting in a 65-year-old man. The symptoms were nonspecific and easily mistaken for other postoperative complications. Diagnosis was based on finding of adrenal hemorrhage on computed tomogram and confirmed biochemically with an adrenal stimulation test. Corticosteroid therapy was curative. PMID- 1637234 TI - Combined maze procedure and septal myectomy in a septuagenarian. AB - A 75-year-old woman with refractory paroxysmal atrial fibrillation and hypertrophic obstructive cardiomyopathy underwent a successful combined maze procedure and septal myectomy. Postoperative episodes of atrial fibrillation and flutter occurred only during periods of bradyarrhythmia and did not recur with atrial inhibited pacing. PMID- 1637235 TI - Tracheoesophageal fistula after chemotherapy for lymphoma. AB - We present a case of tracheoesophageal fistula that occurred after chemotherapy for stage IV B Hodgkin's lymphoma. We outline our surgical management of the case and advocate the use of a single-stage repair in selected cases. PMID- 1637236 TI - Congenital aortic stenosis and patent ductus arteriosus in the adult. AB - Concurrent aortic stenosis and patent ductus arteriosus are not infrequent in children but are rare in adults. An adult case is described with diagnosis by cardiac catheterization and magnetic resonance imaging and with management by combined aortic valve replacement and patent ductus ligation. Review of the English-language literature produced only 8 such cases in adults, 2 of which were managed by a single-stage operation. Successful diagnosis in the adult requires careful observation at cardiac catheterization, and simultaneous valve replacement and ductus ligation may be a useful option in patient management. PMID- 1637237 TI - Extracardiac total cavopulmonary connection. AB - We report the case of a 6-year-old child who underwent definitive conversion to the Fontan circulation using a newly conceived operative technique. This new procedure allows the operation to be performed as a totally extracardiac operation and is based on the hydrodynamic principles of the total cavopulmonary connection. PMID- 1637239 TI - Approach for insertion of aortic composite valve grafts. AB - The usual methods for the reattachment of the coronary ostia to the ascending aortic conduit have several disadvantages and potential complications. A novel, straight-forward technique is described that allows for tension-free anastomoses to be constructed with minimal risk of blood loss and a reduced risk of reoperation for false aneurysms at the anastomoses. PMID- 1637238 TI - Safe intraaortic balloon pump placement through the ascending aorta using transesophageal ultrasound. AB - Intraaortic balloon pumping salvages a substantial number of patients who fail to be weaned from cardiopulmonary bypass after an open heart operation. Patients with severe peripheral vascular disease may require ascending aortic balloon pump insertion. We describe a simple method of direct aortic puncture for intraaortic balloon pump placement using transesophageal ultrasound as a means of avoiding complications during insertion and documenting correct balloon position. PMID- 1637240 TI - Method of single-lung transplantation in the absence of a left atrial cuff. AB - A method used clinically for anastomosing the pulmonary veins to the left atrium, in the absence of a left atrial cuff, during single-lung transplantation by reconstructing the atrium with pericardium is described. Postoperative ventilation/perfusion scans show normal pulmonary blood flow. PMID- 1637241 TI - Right internal mammary artery extended with an inferior epigastric artery for circumflex and right coronary bypass. AB - The right in situ internal mammary artery extended end to end with a free inferior epigastric artery was used through the transverse sinus for sequential grafting to one marginal branch of the circumflex artery and one or both distal branches of the right coronary artery. This procedure was applied in 5 patients with three-vessel disease who received in addition a left in situ internal mammary artery as a sequential graft to the left anterior descending coronary artery and one of its diagonal branches. The postoperative course was uneventful in all cases. A postoperative coronary angiogram obtained on day 10 in 4 patients showed all the grafts and anastomoses patent. PMID- 1637242 TI - Cervical esophago-esophageal anastomosis. AB - We describe our results with cervical esophagoesophageal anastomosis. This approach has been used with success in 4 patients. It has the advantage of avoiding esophagectomy in patients with benign disease and allows restoration of esophageal continuity in patients having limited options for esophageal replacement. PMID- 1637243 TI - Current morbidity, mortality, and survival after bronchoplastic procedures for malignancy. AB - The number of patients reported to have undergone bronchoplastic procedures has increased nearly fourfold in the past decade. These techniques represent excellent surgical therapy for patients with benign endobronchial lesions, traumatic airway disruptions, or tumors of low-grade malignant potential, and for select patients with surgically resectable lung cancer. Eighty-nine percent of bronchoplastic procedures are performed for malignancy. We reviewed 1,915 bronchoplastic procedures for carcinoma reported over the past 12 years to determine the incidence of complications and survival. Complications included local recurrence (10.3%), 30-day mortality (7.5%), pneumonia (6.7%), atelectasis (5.4%), benign stricture or stenosis (5.0%), bronchopleural fistulas (3.5%), empyema (2.8%), bronchovascular fistulas (2.6%), and pulmonary embolism (1.9%). Results were further stratified into sleeve lobectomy and sleeve pneumonectomy groups. Five-year survivals for stage I, II, and III carcinoma were 63%, 37%, and 21%, respectively. Sleeve lobectomy for carcinoma extends surgical therapy to select patients with complication rates comparable to pneumonectomy and long-term survival similar to that for conventional resections. PMID- 1637244 TI - 1985: Fluorocarbons: a potential treatment of cerebral air embolism in open-heart surgery. 1992 update. PMID- 1637245 TI - Retrograde disc escape in a Harken mitral valve prosthesis. PMID- 1637246 TI - Coronary bypass graft aneurysm. PMID- 1637247 TI - Role of the bronchial arteries in lung function. PMID- 1637248 TI - Surgical stabilization of the flail chest. PMID- 1637249 TI - Bronchial stump closure. PMID- 1637250 TI - Types of alcoholics, I. Evidence for an empirically derived typology based on indicators of vulnerability and severity. AB - An empirical clustering technique was applied to data obtained from 321 male and female alcoholics to identify homogeneous subtypes having discriminative and predictive validity. The clustering solution identified two "types" of alcoholics who differed consistently across 17 defining characteristics in the male and female samples. One group, designated type A alcoholics, is characterized by later onset, fewer childhood risk factors, less severe dependence, fewer alcohol related problems, and less psychopathological dysfunction. The other group, termed type B alcoholics, is characterized by childhood risk factors, familial alcoholism, early onset of alcohol-related problems, greater severity of dependence, polydrug use, a more chronic treatment history (despite their younger age), greater psychopathological dysfunction, and more life stress. The two types also differed with respect to treatment outcome assessed prospectively at 12 and 36 months. The results are consistent with historical and contemporary typological theories that have postulated similar subgroups of alcoholics. The findings suggest that an empirically derived, multivariate typology of alcoholism has theoretical implications for explaining the heterogeneity among alcoholics and may provide a useful basis for predicting course and estimating treatment response. PMID- 1637251 TI - The Comprehensive Assessment of Symptoms and History (CASH). An instrument for assessing diagnosis and psychopathology. AB - The Comprehensive Assessment of Symptoms and History was developed for research studies of schizophrenia spectrum conditions and affective spectrum conditions. It is designed to provide a comprehensive information base concerning current and past signs and symptoms, premorbid functioning, cognitive functioning, sociodemographic status, treatment, and course of illness. Because the information base is broad, it is not wedded to a specific diagnostic system but rather permits clinicians and investigators to make diagnoses using a wide range of systems, including Research Diagnostic Criteria, DSM-III, DSM-III-R, and the International Classification of Diseases. Given the fact that disorders in psychiatry are not defined at the etiological or pathophysiological level, diagnostic criteria are prone to ongoing revision as our knowledge base changes. Research strategies suggest that investigators should maintain a flexible database to permit them to adapt to changes in diagnostic systems, to do comparative nosological studies, and, ultimately, to develop new diagnostic systems based on knowledge concerning the underlying neurobiological nature of disorders. Because it provides a comprehensive information base, the Comprehensive Assessment of Symptoms and History facilitates research of this type. Extensive developmental work has been done with the Comprehensive Assessment of Symptoms and History, including interrater and test-retest reliability studies, validity studies, training programs, and data entry programs. PMID- 1637252 TI - The Structured Clinical Interview for DSM-III-R (SCID). I: History, rationale, and description. AB - The history, rationale, and development of the Structured Clinical Interview for DSM-III-R (SCID) is described. The SCID is a semistructured interview for making the major Axis I DSM-III-R diagnoses. It is administered by a clinician and includes an introductory overview followed by nine modules, seven of which represent the major axis I diagnostic classes. Because of its modular construction, it can be adapted for use in studies in which particular diagnoses are not of interest. Using a decision tree approach, the SCID guides the clinician in testing diagnostic hypotheses as the interview is conducted. The output of the SCID is a record of the presence or absence of each of the disorders being considered, for current episode (past month) and for lifetime occurrence. PMID- 1637253 TI - The Structured Clinical Interview for DSM-III-R (SCID). II. Multisite test-retest reliability. AB - A test-retest reliability study of the Structured Clinical Interview for DSM-III R was conducted on 592 subjects in four patient and two nonpatient sites in this country as well as one patient site in Germany. For most of the major categories, kappa s for current and lifetime diagnoses in the patient samples were above .60, with an overall weighted kappa of .61 for current and .68 for lifetime diagnoses. For the nonpatients, however, agreement was considerably lower, with a mean kappa of .37 for current and .51 for lifetime diagnoses. These values for the patient and nonpatient samples are roughly comparable to those obtained with other structured diagnostic instruments. Sources of diagnostic disagreement, such as inadequate training of interviewers, information variance, and low base rates for many disorders, are discussed. PMID- 1637254 TI - Sleep in schizophrenic patients on and off haloperidol therapy. Clinically stable vs relapsed patients. AB - We examined the state-dependent contribution of neuroleptic withdrawal and psychotic relapse in influencing sleep measures. Eighteen clinically stable male schizophrenic patients taking haloperidol were studied with 3 nights of polysomnography for baseline measures and again after neuroleptic withdrawal. Sleep measures were also obtained at the point of relapse (n = 9) or after a 6 week drug-free period if the patient remained clinically stable (n = 9). Neuroleptic withdrawal led to a global deterioration of rapid eye movement and non-rapid eye movement sleep and a reduction of rapid eye movement latency in both groups. Relapsers differed from nonrelapsers in that they had a larger decrease in total sleep time, sleep efficiency, total non-rapid eye movement sleep, and stage 2 sleep. The level of psychosis was inversely correlated with sleep efficiency, total sleep time, and stage 4 sleep in the drug-free patients. Our data suggest that clinical state needs to be identified in sleep studies of drug-free patients. PMID- 1637255 TI - Oral heparin normalizes blood pressure and elevated cytosolic calcium in hypertensive rats. AB - Increased calcium uptake in vascular tissue, leading to elevated cytosolic free calcium has been implicated in the pathophysiology of hypertension. This study examined the effect of oral heparin on systolic blood pressure, platelet cytosolic free calcium and aortic calcium uptake in spontaneously hypertensive and normotensive Wistar-Kyoto rats. Starting at age 12 weeks, each strain of rats were divided into 2 groups (6 animals in each group); the control group was placed on H2O (100%) and the experimental group was placed on H2O with heparin (0.5 mg sodium heparin/ml H2O) for a period of nine weeks. At 21 weeks, systolic blood pressure, platelet cytosolic free calcium and aortic calcium uptake were significantly higher in spontaneously hypertensive rats on water compared with spontaneously hypertensive rats on heparin and Wistar-Kyoto rats on water and on heparin. Oral heparin treatment normalized the elevated platelet cytosolic free calcium, aortic calcium uptake and systolic blood pressure in spontaneously hypertensive rats but had no effect on Wistar-Kyoto rats. Heparin also prevented onset of adverse renal vascular changes observed in spontaneously hypertensive rats. Oral heparin treatment did not cause abnormal hematological, biochemical or pathological changes in rats. PMID- 1637256 TI - Post-marketing surveillance of probucol (Sinlestal) in Japan. AB - We surveyed the efficacy and safety of probucol (Sinlestal) in 6,002 patients with hyperlipidemia during the past six years between Oct., 1984 and Sep., 1990. Probucol was usually administered for more than 8 weeks at a dose of 500 mg per day and effects on serum lipids and adverse drug events (ADEs) were investigated. Total cholesterol (TC), triglycerides (TG) and HDL cholesterol (HDL) significantly decreased by 16-20%, 6-9% and 15-20% respectively. Further, LDL cholesterol (LDL) decreased by 15-19%. ADEs were reported in 2.7% (161/6,002 subjects), but severity was mild or moderate. In addition to survey in 6,002 patients, the effect on regression of xanthomas and safety in long-term administration of over one year was investigated in 44 and 142 patients, respectively. Regression of xanthoma was observed in 63.6% (28/44 subjects). Probucol was well tolerated in long-term administration. These PMS results showed probucol to possess good therapeutic efficacy and safety. PMID- 1637258 TI - Analysis of stress-strain curves at fast and slow velocities of loading in vitro in the transverse section of the rat incisor periodontal ligament following the administration of beta-aminopropionitrile. AB - The in vitro mechanical properties of this ligament were examined by analysing the stress-strain curve obtained from a transverse section of the mandible. Mechanical measures were compared between normal rats and lathyritic rats given drinking water containing 0.2% of beta-aminopropionitrile (BAPN) for 20 days, and between the velocity of loading at 10(4) and 1 mm/24 h. The daily dose of BAPN decreased gradually because the body weight increased gradually. At the velocity of 10(4) mm/24 h, the maximum shear stress, elastic stiffness and failure strain energy density in the experimental subgroup fell to 43-50% of the control values, and at 1 mm/24 h to 71-80%. The maximum strains were not significantly different between the control and experimental subgroups either at 10(4) or at 1 mm/24 h. In the control subgroups, the maximum shear stress, elastic stiffness and failure strain energy density at 1 mm/24 h fell to 0.04-0.30% of those at 10(4) mm/24 h, and in the experimental subgroups to 0.08-0.43%. The maximum strains at 1 mm/24 h were 1.7-1.8 times greater than those at 10(4) mm/24 h in both the control and experimental subgroups. It is assumed that changes in the mechanical properties of the periodontal ligament were caused by inhibition of maturation of the periodontal collagen fibres. Assuming that the periodontal ligament is viscoelastic in nature, it is suggested that the main component reacting at 10(4) mm/24 h was an elastic one and that both components, with emphasis on the viscous one, interact at 1 mm/24 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637257 TI - Effects of probucol on low-density lipoprotein catabolism in guinea pigs. AB - We studied the effects of administering probucol on the catabolism of low density lipoprotein (LDL) in guinea pigs. Probucol administration significantly lowered the levels of total and LDL-cholesterol in animals given either normal chow or the high cholesterol (1% W/W) diet. High-density lipoprotein cholesterol was decreased significantly in the animals fed cholesterol, but not normal chow diet. Triglyceride levels were unaffected in both groups. No significant changes were observed in the LDL receptor-dependent and LDL receptor-independent catabolism of native LDL and LDL obtained from a probucol-treated patient. However, when the LDL isolated from a probucol-treated patient was injected, the fractional catabolic rate was significantly lower than that of injected native LDL. This study indicates that probucol lowered the plasma LDL cholesterol level neither by an increased catabolism of LDL via an LDL receptor nor an LDL receptor independent pathway. PMID- 1637260 TI - Short electromyographic bursts in the rabbit digastric muscle during the jaw closing phase. AB - Masseter and digastric muscle activities and jaw movement trajectories were recorded in freely moving rabbits during eating. The patterns in these trajectories and activities were similar to those described in previous studies on restrained animals. Although the duration of masticatory sequences, which started with food intake followed by grinding movements and ended by swallowing, varied, the total number of chewing cycles in a chain of masticatory sequences was consistent (1043 +/- 51, mean +/- SD; n = 5, for chow pellets) among the animals tested. When animals ate hard foods, extra bursts in the digastric electromyograms occurred frequently in the jaw-closing phase. The digastric activities were rather short (6.1 +/- 1.0 ms; n = 100) and the amplitude of these digastric short bursts (DSBs) was much larger (1.69 +/- 0.81 mV; n = 100) than in the opening phase (0.56 +/- 0.33 mV; n = 100), which actually depressed the jaw. When a soft food (bread) was tested, this activity was not observed. The proportion of occurrences of the DSB in a chewing cycle was high at the slow closing phase, indicating that the DSBs were due to tooth contacts during food crushing. Of 1035 chewing cycles examined in the five animals, 124 were associated with a DSB and 415 cycles with a masseter inhibitory period (MIP). The proportion of the occurrences of the MIP was significantly larger than that of the DSBs. Of 124 DSBs, 85 (68.5 per cent) coincided with an MIP. Four were not associated with clear MIPs, although there was masseter activity at the time of the DSBs. The other 35 DSBs were out of phase with the masseter bursts, although still in a closing phase. The durations of the MIPs accompanied by a DSB were significantly longer than those not so associated. The DSB may be a reflex response mediated by periodontal mechanoreceptors when the upper and lower teeth come together while chewing hard food. The reflex arc for the DSB may be independent of that for the MIP, and the threshold for the DSB may be higher. PMID- 1637259 TI - Mast cell heterogeneity in various oral mucosal sites in the rat. AB - Two distinct types of mast cells are recognized in the rat: connective tissue mast cells (CTMCs), found in the peritoneal cavity, skin, tongue, etc. and mucosal mast cells (MMCs), found in the intestinal mucosa. The two subsets differ functionally and can be defined by histochemical methods. The aim here was to characterize the mast cell population in various oral mucosal sites. Biopsies were taken from the tongue, buccal mucosa, gingival mucosa and intestine (jejunum) of 20 rats. For optimal preservation of the MMCs, a fixative with low aldehyde concentration and low pH was used. The biopsies were embedded in paraffin. The first of three consecutive sections (5 microns) was stained with toluidine blue for 30 s, the second with toluidine blue for 7 days and the third with astra blue/safranine. Cells positive with toluidine blue after 30 s were classified as CTMCs, and those positive after 7 days but not after 30 s as MMCs. Cells positive to safranine in the astra blue/safranine staining sequence were classified as CTMCs and those positive to astra blue as MMCs. The total number of mast cells was similar in the superficial layers of all oral tissues studied. There were more mast cells in the deeper than in the superficial portions of the tongue. Mast cells with staining characteristics and size similar to those observed in the intestinal mucosa (MMCs) were found together with 'classical' connective tissue mast cells (CTMCs). The results suggest that the mast cell population of oral mucosal tissues of the rat contains both CTMC- and MMC-like cells. PMID- 1637261 TI - Fluoride binding by matrix proteins in rat mineralizing tissue. AB - Chronic fluoride exposure in vivo results in alterations in the formation of mineralizing tissues. One possible mechanism for the formation of fluorosed tooth enamel and bone is a binding of fluoride to matrix proteins, resulting in an alteration in their structure and function. Studies were designed to investigate fluoride binding to matrix proteins in vivo and their possible role in fluorosis. Rats were given either 0 or 100 parts/10(6) fluoride in drinking water for 6 weeks to allow the formation of fluorotic mineralizing tissues. The animals were killed by CO2 inhalation, and the enamel and bone were analysed for fluoride and calcium. Matrix binding by fluoride in enamel was determined after extraction of proteins from undemineralized matrix. In bone, the matrix was demineralized and F, Ca and P were determined in both ashed and unashed samples. The studies showed ionic binding of fluoride to the matrix in both enamel and bone, possibly associated with calcium binding by the matrix. There was no difference in the amount of matrix-bound fluoride in control as compared to fluorosed bone or maturation-stage enamel. This indicates that although matrix proteins can bind fluoride, it is not likely that this mechanism is important in the formation of fluorosed mineralizing tissues. PMID- 1637262 TI - Effects of transforming growth factor-beta 1 on cultured dental follicle cells from rat mandibular molars. AB - Analysis of the total proteins secreted by cultured dental follicle cells revealed that transforming growth factor-beta 1 (TGF-beta 1) stimulated them to secrete more extracellular matrix proteins into a serum-free medium than did follicle cells not exposed to the growth factor. Electrophoresis and scanning densitometry showed that secretion of all the major proteins was increased by exposure to the growth factor but the amounts ranged from a 66% increase for one of the procollagen chains to a 7% increase for fibronectin. Immunofluorescence using anti-type I collagen and anti-fibronectin showed that the intracellular concentration and intracellular localization of the antibodies was not changed by incubating the cells with the growth factor. The growth factor did not cause an increase in cell number but did modify the association of the cells in the culture, causing them to aggregate into clusters whereas the control cells formed a confluent monolayer. These results suggest that TGF-beta 1 may signal the fibroblasts of the dental follicle to secrete the extracellular matrix needed for its development into a periodontal ligament. PMID- 1637263 TI - Ultrastructural quantification of collagen fibrils in the central region of the articular disc of the temporomandibular joint of the cat and the guinea pig. AB - This quantitative ultrastructural analysis was made on articular discs from four guinea pigs and four cats. Mean diameters of collagen fibrils were small (approximately 45 nm) and showed unimodal distributions. These features are consistent for connective tissues subjected to compressional forces. The relatively high percentage volume of the extracellular matrix occupied by collagen in the articular disc of the guinea pig (approximately 60 per cent) and the presence of crimping is, however, more typical of a connective tissue subjected to tension. Two differences were discernible between the collagen in the articular discs of the guinea pig and cat. First, the percentage volume occupied by collagen for the guinea pig disc was significantly higher than for the cat. Second, the frequency distribution of collagen fibril diameters for the cat, although unimodal, was skewed. These differences possibly reflect the different types of movement at the temporomandibular joints in the two species. PMID- 1637264 TI - Flow cytometric evaluation of phagocytosis by peripheral blood polymorphonuclear leucocytes in human periodontal diseases. AB - The complement-dependent phagocytic functions of polymorphonuclear leucocytes (PMNL) in peripheral blood from 15 patients with localized juvenile periodontitis (LJP), 13 with generalized juvenile periodontitis (GJP) and 52 with adult periodontitis (AP), and from 30 normal subjects as controls were measured by flow cytometry. Heparinized blood was collected and incubated with fluorescent microspheres, and erythrocytes were removed. By means of single-cell analysis the percentage of phagocytosing cells (% phagocytosis) and the mean number of microspheres phagocytosed by one PMNL (degree of phagocytosis; d-phagocytosis) were measured. Some but not all patients with LJP (53%) and GJP (46%) showed consistently low % phagocytosis and d-phagocytosis. On the other hand, only 6% of AP patients and no healthy subjects showed a reduction of PMNL phagocytosis. Phagocytosis was unchanged after initial periodontal treatment in all subjects, suggesting the depression of PMNL phagocytosis may not be a transient phenomenon associated with periodontal status. Furthermore, PMNLs from the LJP patients that showed depressed phagocytic function exhibited depressed phagocytic responses with either autologous or normal plasma, while control PMNLs with either normal or the patients' plasma showed normal responses. These results suggested that the depressed phagocytic responses in LJP patients could be due to cell-associated defect(s) on the PMNL. PMID- 1637265 TI - Immunohistochemical detection of androgen receptors in human oral mucosa. AB - Oral mucosal biopsies from 11 healthy volunteers, 7 women and 4 men, were analysed for the localization of androgen, oestrogen and progesterone receptors. The samples were dissected as quickly as possible and immediately frozen in liquid nitrogen to be stored at -70 degrees C. Only androgen receptors could be detected by the methods used. These were mainly located in the nuclei of basal epithelial cells, and to some extent in the nuclei of fibroblasts and endothelial cells. Failure in the localization of oestrogen and progesterone receptors might have been due either to low numbers of receptors or to the insensitivity of antibodies used. The method is thus suitable only for detecting androgen receptors. PMID- 1637266 TI - Chondroitin sulfate-induced generation of epiretinal membranes. AB - Previous investigations have examined the role of serum and retinal pigment epithelium-derived factors in the elaboration of epiretinal membranes. Alternatively, the contribution of the insoluble interphotoreceptor matrix, known to contain chondroitin-sulfate-containing proteoglycans, in the generation of epiretinal membranes, has not been evaluated, to our knowledge. To investigate the potential role of chondroitin sulfates in eliciting epiretinal membranes, chondroitin sulfate glycosaminoglycans were injected into the vitreous cavity of rabbits. Examination demonstrated epiretinal membranes in 86% of eyes receiving chondroitin-6-sulfate. Temporal development of chondroitin sulfate glycosaminoglycan-induced epiretinal membranes was categorized into three distinct stages: a preretinal cell stage 1 to 3 weeks following injection, a glial "tuft" stage at 3 to 6 weeks, and a "mature" complex membrane stage at 6 weeks or later. Our results suggest that intravitreal administration of chondroitin sulfate glycosaminoglycan, components of insoluble interphotoreceptor matrix proteoglycans, may elicit the generation of epiretinal membranes, even in the absence of retinal disruption. PMID- 1637267 TI - Loiasis in Maryland. PMID- 1637268 TI - A surgical procedure to minimize lower-eyelid retraction with inferior rectus recession. AB - Advancement of the capsulopalpebral head at the time of inferior rectus recession has been described as a technique to minimize postoperative lower-eyelid retraction. In a prospective randomized masked clinical trial, this technique combined with inferior rectus recession was compared with inferior rectus recession alone, with respect to post-operative lower-eyelid retraction. The mean (+/- SD) postoperative lower-eyelid retraction was 0.7 +/- .82 mm for patients in whom the capsulopalpebral head was advanced, as opposed to 1.3 +/- .85 mm for the control group. This difference was statistically significant (Student's t = 2.787; P = .006). PMID- 1637269 TI - Infectious endophthalmitis following sutureless cataract surgery. PMID- 1637270 TI - Infectious endophthalmitis following sutureless cataract surgery. PMID- 1637271 TI - Infectious endophthalmitis following sutureless cataract surgery. PMID- 1637272 TI - Infectious endophthalmitis following sutureless cataract surgery. PMID- 1637273 TI - Infectious endophthalmitis following sutureless cataract surgery. PMID- 1637274 TI - Intraocular cilia after penetrating eye injury. PMID- 1637275 TI - Iris nodule and intralenticular abscess associated with Propionibacterium acnes endophthalmitis. PMID- 1637276 TI - Recommendations for better Medicare performance. PMID- 1637277 TI - Dyslexia at The New York Times: (mis)understanding of parallel visual processing. PMID- 1637278 TI - Excimer laser photorefractive keratectomy in high myopia. A multicenter study. AB - Excimer photorefractive keratectomy was performed at three centers on 16 highly myopic eyes (8 diopters [D] or more) and followed up for 6 months. Ablation depths ranged from 137 to 230 microns. The preoperative spherical equivalent of myopia ranged from -8.62 D to -14.50 D (mean +/- SD, -11.57 +/- 1.62 D). Six months after surgery, the mean refraction (spherical equivalent) was -0.90 +/- 2.13 D. Eleven of 16 eyes achieved refractions within 2 D of that attempted. All eight patients at one site were treated with a maximum-beam diameter of 6.0 mm and were corrected to within 2 D of that attempted, and all were 20/40 or better uncorrected. Three of eight eyes at the other two sites were treated with a 5.5- or 5.6-mm maximum-beam diameter, which achieved corrections within 2 D of that attempted. The epithelium healed within 3 to 4 days, and there were no erosions. Mild subepithelial reticular haze, similar to that seen with excimer photorefractive keratectomy for lower myopia, was seen in all patients, with two patients experiencing more significant corneal haze. This peaked at 3 to 6 weeks and then gradually diminished. All but two patients had a return of their best corrected preoperative visual acuity to within one Snellen line at 6 months. This preliminary study shows excimer photorefractive keratectomy to be a promising surgical treatment for patients with higher myopia. PMID- 1637280 TI - Contrast sensitivity in patients with nuclear cataracts. AB - Spatial contrast sensitivity and lens density were measured in 30 subjects (18 patients with pure nuclear cataracts and 12 age-matched controls). Contrast sensitivity was assessed using two techniques: a conventional monitor method in which gratings were viewed through the cataract (overall spatial contrast sensitivity) and a laser interferometer method in which gratings were formed directly on the retina (interferometric spatial contrast sensitivity), thus reducing the effect of an opaque lens on grating contrast. The degree of lens nuclear opacity was measured by assessing the density of Zeiss Scheimpflug slit lamp video camera images. A contrast sensitivity loss was found by using both methods; this reduction reached statistical significance only when monitor stimuli were used. There was a significant correlation between lens nuclear density and sensitivity loss at spatial frequencies from 4 to 16 cycles/degree (r = .56 to .79 and P less than .05 to less than .001). A correlation coefficient of .82 (P less than .001) characterized the relationship between visual acuity (log of the minimal angle of resolution) and lens density. Nuclear lens opacity significantly affects contrast sensitivity; pure nuclear cataracts produce spatial visual losses at intermediate and high spatial frequencies. PMID- 1637279 TI - The effect of topical corticosteroids on refractive outcome and corneal haze after photorefractive keratectomy. A prospective, randomized, double-blind trial. AB - In this study, we report the results of a prospective, double-blind trial to determine whether high-dose topical corticosteroids have an effect on refractive outcome or anterior stromal haze after photorefractive keratectomy. A total of 113 patients were allocated randomly to either placebo- or steroid-treated groups (0.1% dexamethasone metasulphobenzoate for 3 months) and underwent either -3.00 diopter (D) or -6.00-D procedures. At 6 weeks, the mean change in refraction was significantly greater in the steroid-treated group than in the placebo-treated group (-3.00-D group, P = .0015; -6.00-D group, P = .0011). However, when corticosteroids were discontinued at 3 months, this difference became statistically insignificant. There was no statistically significant effect on anterior stromal haze at any stage. Since long-term use of corticosteroids to maintain the initial beneficial effect on refraction would be unacceptable, we conclude that these agents should not be used after photorefractive keratectomy. PMID- 1637281 TI - Rotation of posterior chamber intraocular lenses for management of lens associated recurring hyphemas. AB - Management of recurring hyphemas associated with posterior chamber intraocular lenses may include a combination of medical, laser, and surgical modalities. Miotic and laser therapies have often failed, and surgical treatment has primarily relied on removal of the offending lens. We describe herein a method for rotation of the intraocular lens that provides an effective means of preventing one form of recurrent intraocular hemorrhage. PMID- 1637282 TI - Complications of glaucoma surgery. Ocular decompression retinopathy. AB - In seven eyes of four patients, retinal hemorrhages were observed following trabeculectomy under both local and general anesthesia. The hemorrhages were diffuse, both deep and superficial, and many had white centers when first observed. Two patients were young healthy male myopes undergoing primary trabeculectomy. The third patient was a young man with chronic uveitis. The fourth patient was an elderly man with primary open angle glaucoma who had an acute rise in intraocular pressure following cataract extraction. Intraocular pressure and visual results appeared unaffected by the hemorrhages. Retinal hemorrhages associated with ocular decompression appear to be relatively benign. PMID- 1637283 TI - Fine-needle aspiration biopsy of the iris. AB - Fine-needle aspiration biopsy (FNAB) specimens obtained from nine consecutive iris lesions were examined. The lesions included primary malignant melanoma (four cases), metastatic melanoma, metastatic adenocarcinoma, leukemic infiltrate, lymphocytic infiltrate, and epithelial ingrowth. Subsequent histopathologic correlation was performed in all cases. Patient treatment influenced by the results of the FNABs included enucleation (three cases), clinical observation (two cases), external beam irradiation (two cases), resection, and radioactive plaque application. No complications occurred from the FNABs. Fine-needle aspiration biopsy of the iris can be performed with local anesthesia at the slit lamp as an outpatient procedure. In general, FNAB is a safe, effective method of obtaining diagnostic material from primary neoplastic, secondary neoplastic, and degenerative processes involving the iris. Limitations of the procedure include discrepancies in interpretation of the cytologic study and inadequate specimen. PMID- 1637284 TI - Unsuccessful excimer laser phototherapeutic keratectomy. Clinicopathologic correlation. AB - A 46-year-old man underwent phototherapeutic keratectomy with a 193-nm excimer laser in an attempt to remove a superficial corneal scar that had been present for 36 years. The scar proved to be resistant to ablation with the laser, while relatively normal stroma was easily ablated. Histopathologic examination of the corneal button removed 3 months after excimer laser surgery revealed absence of Bowman's membrane in the area of ablation, superficial stromal disorganization and scarring, raised nodules of collagenous tissue extending into the epithelium, and no calcification within the lesion. Ultrastructural examination was remarkable for irregularly oriented collagen fibers within the scar. The resistance of this lesion to excimer laser ablation appears to have been the consequence of marked differences in rates of ablation between normal stroma and the very long-standing scar. PMID- 1637285 TI - What is actually stained by rose bengal? AB - It has been believed that 1% rose bengal does not stain normal, healthy cells but rather stains degenerated or dead cells and mucous strands. In contrast to this conventional knowledge, we discovered that both commercial additive-containing and additive-free rose bengal solutions stained four different types of healthy cultured cells, including rabbit corneal epithelial cells. Rose bengal staining was rapid, dose dependent, predominantly nuclear, and detectable with the naked eye at concentrations as low as 0.05% and 0.025% for the commercial additive containing or additive-free solutions, respectively, and with the fluorescence microscope at a concentration of 0.001%. It is surprising to discover that rose bengal is not a vital dye; after staining, cells actually lost vitality, as evidenced by instant morphologic changes, subsequent loss of cellular motility, cell detachment, and cell death. Such an intrinsic toxic effect was augmented by light exposure. The rose bengal staining of live as well as detergent-treated (Triton X-100) cells could be blocked by such tear components as mucin and albumin, suggesting that normally negative rose bengal staining is due to the protective function of the preocular tear film, ie, staining is not dictated by lack of cell vitality. These data indicate that rose bengal staining ensues whenever there is poor protection of surface epithelium by the preocular tear film; this represents a new interpretation for rose bengal stains seen in various ocular surface disorders. PMID- 1637286 TI - Multifocal corneal topographic changes with excimer laser photorefractive keratectomy. AB - Excimer laser photorefractive keratectomy can flatten the central cornea, thereby eliminating myopic refractive errors; in older patients, however, presbyopia limits satisfaction. Computer-assisted topographic analysis of corneas after refractive surgery indicates that a minority of patients achieve a multifocal lens effect, such that they maintain reasonable acuity over a range of defocus. We have purposefully attempted to create a multifocal refractive effect and have analyzed the subsequent topographies quantitatively to determine if multifocality was achieved. In corneas not operated on and plastic hemispheres, a fairly small range of corneal powers is observed; the range of powers is increased after a monofocal ablation. After multifocal ablations, a greater spread of surface powers is observed, often with a bimodal distribution, indicative of an apparent multifocal effect. These observations suggest that in some patients undergoing photorefractive keratectomy for myopia, it may be possible to reduce symptoms of presbyopia, although a decrease in image contrast or monocular diplopia may complicate this approach. PMID- 1637287 TI - Isolation, by affinity chromatography and gel filtration in 8 M-urea, of an active subunit from the anti-(blood-group A+N)-specific lectin of Moluccella laevis. AB - The lectin from Moluccella laevis seeds agglutinates specifically blood-type-A and -N erythrocytes, and both activities are inhibited by micromolar concentrations of N-acetyl-D-galactosamine. The lectin consists of three subunits: a 67 kDa heterodimer, made up of two S-S-linked polypeptides of 28 and 46 kDa, and two non-covalently linked moieties of 26 and 42 kDa, the latter migrating after reduction with an apparent molecular mass of 46 kDa. Here we demonstrate that affinity chromatography of a crude protein fraction from M. laevis seeds on immobilized D-galactose in the presence of 8 M-urea affords a fully active lectin practically devoid of the 42 kDa subunit. We also present data showing that the 26 kDa subunit is devoid of cysteine residues, that the 28 kDa subunit contains two cysteine residues engaged in S-S bonds with the 46 kDa subunit, and that the latter has, in addition, two intramolecular cystine residues. Gel filtration on Sephadex G-150 in 8 M-urea/0.2 M-D-galactose of the lectin, affinity-purified in the presence of urea, afforded a pure 26 kDa subunit which exhibited both anti-A and anti-N activity, as well as high specificity for N-acetyl-D-galactosamine. In addition to demonstrating that the lectin is unusually stable and retains its carbohydrate-binding activity in 8 M-urea, our findings also show that the activity for different blood groups resides in the same subunit. PMID- 1637288 TI - Lipid utilization by human lymphocytes is correlated with high-density lipoprotein binding site activity. AB - The nature and physiological importance of high-density lipoprotein (HDL) binding sites on unstimulated (resting) and mitogen-activated (blast) human peripheral blood lymphocytes were investigated. Specific HDL binding on resting and blast T lymphocytes was saturable at 50 micrograms of 125I-HDL/ml and of high affinity, with Kd values of 8.1 x 10(-8) M and 6.5 x 10(-8) M, respectively, and Bmax. values of 79 ng and 180 ng/mg of cell protein respectively at 4 degrees C. Binding of HDL double-labelled with fluorescent dioctadecylindocarbocyanine (Dil) and isotope (125I) as well as of single fluorescence- or isotope-labelled HDL was inhibited competitively by HDL apoproteins. Studies of the cholesterol flux between the cells and HDL showed that HDL, low-density lipoprotein (LDL) or BSA at a concentration of 100 micrograms/ml in the tissue culture medium did not result in a significant difference in exogenous [3H]cholesterol efflux from the cell membrane at 37 degrees C. Proliferating T-blasts incorporated more cholesterol from HDL or LDL than did resting lymphocytes. When the cells were pulsed with 125I-HDL and chased in fresh lipid-free medium, up to 80% of the radioactivity released was not precipitable with trichloroacetic acid. This percentage decreased in a competitive manner when unlabelled HDL was present in the chase incubation medium. Finally, cultivation of lymphocytes with conditioned medium from macrophages increased Dil-HDL binding/uptake, while it was decreased by mevinolin-induced inhibition of hydroxymethylglutaryl-coA reductase. In conclusion, human lymphocytes possess a HDL binding site (receptor) responsible for lipid binding/uptake and concomitant internalization and degradation of apoproteins from HDL, but not for reverse cell membrane cholesterol transport. The activity of the binding site is up-regulated during cell proliferation and down-regulated during cell growth suppression. PMID- 1637289 TI - Long-chain acyl-CoA ester intermediates of beta-oxidation of mono- and di carboxylic fatty acids by extracts of Corynebacterium sp. strain 7E1C. AB - beta-Oxidation of palmitate and tetradecanedioic acid was studied in cell-free extracts of the Gram-positive bacterium Corynebacterium sp. strain 7E1C, and the acyl-CoA ester intermediates formed were analysed by h.p.l.c. beta-Oxidation assays displayed a lag phase before a constant rate of NAD+ reduction was obtained. The length of the lag phase was inversely proportional to the number of units of activity added to assays. This is a characteristic feature of a system of consecutive reactions proceeding via free intermediates. During beta-oxidation of palmitate all the saturated acyl-CoAs from C16 to C8 were detected together with trace amounts of unsaturated and 3-hydroxy-intermediates. The time-course of intermediate formation again indicated a precursor-product relationship indicative of free intermediates being formed. When 3-hydroxyacyl-CoA dehydrogenase was inhibited by completely removing NAD+ from assays, the major acyl-CoAs, detected during palmitate beta-oxidation were palmitoyl-CoA, hexadeca 2-enoyl-CoA and 3-hydroxypalmitoyl-CoA. These compounds also displayed a precursor-product relationship. Under normal assay conditions the acyl-CoA dehydrogenase(s) are the probable rate-limiting enzyme(s) of the beta-oxidation spiral. These results indicate that in cell-free extracts of Corynebacterium sp. strain 7E1C, beta-oxidation proceeds via free acyl-CoA intermediates and is at variance with the concept of substrate channelling or of a 'leaky hose pipe' model as proposed for mitochondrial beta-oxidation in eukaryotic cells. The significant accumulation of chain-shortened acyl-CoA esters is similar to the situation observed for mammalian peroxisomal beta-oxidation. PMID- 1637290 TI - Regulation of Na+/Ca2+ exchange in the rat pancreatic B cell. AB - Na+/Ca2+ exchange in the B cell was recently characterized by measuring intracellular-Na(+)-dependent 45Ca2+ uptake in isolated rat pancreatic islet cells. The aim of the present study was to investigate the regulation of this process. Extracellular pH (pHo) and intracellular pH (pHi) markedly affected Na+/Ca2+ exchange. A fall of 0.04 unit in pHi decreased the exchange by 45%, whereas a rise of 0.13 unit increased the uptake by 70%. Mitochondrial poisons (oligomycin, antimycin A and 2,4-dinitrophenol) inhibited reverse Na+/Ca2+ exchange by about 25-50%. The exchanger displayed a low Q10 (temperature coefficient), indicating that it is only indirectly dependent on metabolic energy. The phorbol ester phorbol 12-myristate 13-acetate did not affect Na+/Ca2+ exchange. Likewise, lowering the extracellular K+ concentration did not inhibit 45Ca2+ uptake. In conclusion, the pHi and the metabolic state of the cell may represent important modulatory signals by which insulin secretagogues such as glucose could regulate reverse Na+/Ca2+ exchange in the B cell. The process does not appear to co-transport K+ nor to be influenced by protein kinase C. PMID- 1637291 TI - Processing of human pro-lactase-phlorizin hydrolase at reduced temperatures: cleavage is preceded by complex glycosylation. AB - Intracellular processing of human intestinal lactase-phlorizin hydrolase (LPH) includes an essential proteolytic cleavage step that generates the mature brush border enzyme from the single-chain polypeptide precursor (pro-LPH). Previous work in organ culture of small intestinal biopsy samples [Naim, Sterchi & Lentze (1987) Biochem. J. 241, 427-434] has demonstrated that this cleavage occurs intracellularly. Since no intermediate forms of pro-LPH (trimmed or complex glycosylated) could be discerned in pulse-chase analyses it was suggested that the cleavage process occurs at a fast rate. To identify intermediate forms of pro LPH prior to cleavage, I studied the biosynthesis of LPH by employing a pulse chase protocol in mucosa explants (or biopsies) at reduced temperatures (22 degrees C). Here, I could identify by immunoprecipitation with monoclonal anti LPH antibodies four LPH forms that exhibited a product-precursor relationship:mannose-rich precursor (pro-LPHh), trimmed pro-LPH (LPHt), complex glycosylated pro-LPH (pro-LPHc) and cleaved, mature LPH (LPHm). The results clearly indicate that the generation of mature LPH is preceded by complex glycosylation of the precursor form. The fact that this was not previously observed in the same experimental system under normal biosynthetic labelling conditions (37 degrees C) demonstrates that the cleavage process of pro-LPH occurs at a fast rate in the human small intestine. PMID- 1637292 TI - Dissociation between phytohaemagglutinin-stimulated generation of inositol phosphates and Ca2+ increase in human mononuclear leucocytes. AB - We have tested whether phytohaemagglutinin (PHA)-stimulated generation of inositol phosphates (IP) and increases in intracellular Ca2+ can be dissociated in human mononuclear leucocytes. Lowering the incubation temperature from 37 degrees to 25 degrees C decreased PHA-stimulated IP generation by more than 80%, but only marginally affected PHA-stimulated Ca2+ increases. In the absence of extracellular Ca2+, PHA did not stimulate IP generation or Ca2+ increases, although PHA binding to its acceptor sites was not impaired. Increasing extracellular Ca2+ up to 0.15 mM enhanced PHA-stimulated PHA generation but this increase was attenuated by further increasing extracellular Ca2+ to 2.6 mM. Increasing extracellular Ca2+ to 0.3 mM also enhanced PHA-stimulated Ca2+ increases, and further increasing extracellular Ca2+ did not affect it. Co treatment with 100 microM-prostaglandin E2 completely abolished PHA-stimulated IP generation, but inhibited Ca2+ increases by only 20-30%. These results could be explained by IP-generation-independent Ca2+ increases or by non-linear coupling of IP generation to Ca2+ increases. Since the PHA concentrations required to increase Ca2+ were greater than those required for IP generation, the latter hypothesis can be excluded. Furthermore, the Ca2+ ionophore ionomycin increased intracellular Ca2+ and weakly stimulated IP generation, but with very similar concentration-response relationships. Our data suggest that PHA-stimulated IP generation and Ca2+ increases in human mononuclear leucocytes mainly occur independently of one another rather than sequentially. PMID- 1637293 TI - Large inhibitor of metalloproteinases (LIMP) contains tissue inhibitor of metalloproteinases (TIMP)-2 bound to 72,000-M(r) progelatinase. AB - Connective-tissue cells in culture produce a family of metalloproteinases which, once activated, can degrade all the components of the extracellular matrix. These potent enzymes are all inhibited by the tissue inhibitor of metalloproteinases (TIMP), and it was thought that this inhibitor was solely responsible for the inhibition of these enzymes within connective tissue. However, other inhibitors have recently been described, including large inhibitor of metalloproteinases (LIMP) present in the culture medium of human foetal lung fibroblasts. Here we show that a large proportion of the inhibitory activity of LIMP consists of 72,000-M(r)-progelatinase bound to TIMP-2, a recently discovered low-M(r) metalloproteinase inhibitor closely related to TIMP. The physiological implications of the secretion of a complex of 72,000-M(r) progelatinase and TIMP 2 are discussed, and the separation of the complex in 6 M-urea is described. PMID- 1637294 TI - Quantification of apolipoprotein B-48 and B-100 in rat liver endoplasmic reticulum and Golgi fractions. AB - We have developed a method for measurement of apolipoprotein (apo) B-48 and apo B 100 in blood and subcellular fractions of rat liver based on SDS/PAGE followed by quantitative immunoblotting using 125I-Protein A. Standard curves were prepared in each assay using apo B prepared from total rat lipoproteins by extraction with tetramethylurea. Subcellular fractions (rough and smooth endoplasmic reticulum and Golgi fractions) were prepared from rat liver and separated into membrane and cisternal-content fractions. For quantification, membrane fractions were solubilized in Triton X-100, and the apo B was immunoprecipitated before separation by SDS/PAGE and immunoblotting. Content fractions were concentrated by ultrafiltration and separated by SDS/PAGE without immunoprecipitation. Quantification of apo B in subcellular fractions and detection of apo B by immunoblotting yielded consistent results. In all fractions apo B-48 was the major form, accounting for approximately three-quarters of the total apo B. By using marker enzymes as internal standards, it was calculated that all of the apo B was recovered in the endoplasmic reticulum and Golgi fractions, with approximately 80% of each form of apo B in the endoplasmic reticulum. More than 90% of the apo B of the rough- and smooth-endoplasmic-reticulum fractions was membrane-bound, whereas approx. 33 and 15% of the apo B of the cis-enriched Golgi fractions and trans-enriched Golgi fractions respectively were membrane-bound. PMID- 1637295 TI - Effects of clofibric acid on the activity and activity state of the hepatic branched-chain 2-oxo acid dehydrogenase complex. AB - Feeding clofibric acid to rats caused little or no change in total activity of the liver branched-chain 2-oxo acid dehydrogenase complex (BCODC). No change in mass of liver BCODC was detected by immunoblot analysis in response to dietary clofibric acid. No changes in abundance of mRNAs for the BCODC E1 alpha, E1 beta and E2 subunits were detected by Northern-blot analysis. Likewise, dietary clofibric acid had no effect on the activity state of liver BCODC (percentage of enzyme in the dephosphorylated, active, form) of rats fed on a chow diet. However, dietary clofibric acid greatly increased the activity state of liver BCODC of rats fed on a diet deficient in protein. No stable change in liver BCODC kinase activity was found in response to clofibric acid in either chow-fed or low protein-fed rats. Clofibric acid had a biphasic effect on flux through BCODC in hepatocytes prepared from low-protein-fed rats. Stimulation of BCODC flux at low concentrations was due to clofibric acid inhibition of BCODC kinase, which in turn allowed activation of BCODC by BCODC phosphatase. Inhibition of BCODC flux at high concentrations was due to direct inhibition of BCODC by clofibric acid. The results suggest that the effects of clofibric acid in vivo on branched-chain amino acid metabolism can be explained by the inhibitory effects of this drug on BCODC kinase. PMID- 1637296 TI - Amino acid sequence of band-3 protein from rainbow trout erythrocytes derived from cDNA. AB - In this report we present the first complete band-3 cDNA sequence of a poikilothermic lower vertebrate. The primary structure of the anion-exchange protein band 3 (AE1) from rainbow trout erythrocytes was determined by nucleotide sequencing of cDNA clones. The overlapping clones have a total length of 3827 bp with a 5'-terminal untranslated region of 150 bp, a 2754 bp open reading frame and a 3'-untranslated region of 924 bp. Band-3 protein from trout erythrocytes consists of 918 amino acid residues with a calculated molecular mass of 101 827 Da. Comparison of its amino acid sequence revealed a 60-65% identity within the transmembrane spanning sequence of band-3 proteins published so far. An additional insertion of 24 amino acid residues within the membrane-associated domain of trout band-3 protein was identified, which until now was thought to be a general feature only of mammalian band-3-related proteins. PMID- 1637298 TI - Direct electrochemical studies of hydrogenase and CO dehydrogenase. AB - The reduction potentials of two relatively high-molecular-mass enzymes were determined directly at an edge pyrolytic graphite electrode by using square-wave voltammetry. The equilibrium reduction potential versus standard hydrogen electrode was determined for Clostridium pasteurianum hydrogenase I (E'0 = -377 +/- 10 mV; molecular mass 60 kDa) and Rhodospirillum rubrum carbon monoxide dehydrogenase (E'0 = -418 +/- 7 mV; molecular mass 62 kDa). The reduction potential of each enzyme was pH-independent, and one electron was transferred per redox centre. The reduction potential was determined to be identical for the CO dehydrogenase, semi-apo-(CO dehydrogenase), and CO dehydrogenase with carbonyl sulphide (COS) or cyanide bound. The electron-transferring efficiency of CO dehydrogenase was affected by two inhibitors, COS and cyanide, as indicated by a diminished analytic current. PMID- 1637297 TI - Molecular cloning and heterologous expression of a cDNA encoding a mouse glutathione S-transferase Yc subunit possessing high catalytic activity for aflatoxin B1-8,9-epoxide. AB - Resistance to the carcinogenic effects of aflatoxin B1 (AFB1) in the mouse is due to the constitutive expression of an Alpha-class glutathione S-transferase (GST), YcYc, with high detoxification activity towards AFB1-8,9-epoxide. A cDNA clone (pmusGST Yc) for a murine GST Yc polypeptide has been isolated. Sequencing has shown the cDNA insert of pmusGST Yc to be 922 bp in length, with an open reading frame of 663 bp that encodes a polypeptide of M(r) 25358. The primary structure of the murine GST Yc subunit predicted by pmusGST Yc is in complete agreement with the partial amino acid sequence of the aflatoxin-metabolizing mouse liver GST described previously [McLellan, Kerr, Cronshaw & Hayes (1991) Biochem. J. 276, 461-469]. A plasmid, termed pKK-musGST Yc, which permits the expression of the murine Yc subunit in Escherichia coli, has been constructed. The murine GST expressed in E. coli was purified and found to be catalytically active towards several GST substrates, including AFB1-8,9-epoxide. This enzyme was also found to possess electrophoretic and immunochemical properties closely similar to those of the GST Yc subunit from mouse liver. However, the GST synthesized in E. coli and the constitutive mouse liver Alpha-class GST exhibited small differences in their chromatographic behaviour during reverse-phase h.p.l.c. Automated Edman degradation revealed alanine to be the N-terminal amino acid in the GST Yc subunit expressed in E. coli, whereas the enzyme in mouse liver possesses a blocked N-terminus. Although sequencing showed that the purified Yc subunit from E. coli lacked the initiator methionine, the amino acid sequence obtained over the first eleven N-terminal residues agreed with that predicted from the cDNA clone, pmusGST Yc. Comparison of the deduced amino acid sequence of the mouse Yc polypeptide with the primary structures of the rat Alpha-class GST enzymes revealed that it is more closely related to the ethoxyquin-induced rat liver Yc2 subunit than to the constitutively expressed rat liver Yc1 subunit. The significance of the fact that both mouse Yc and rat Yc2 exhibit high catalytic activity towards AFB1-8,9-epoxide, whereas rat Yc1 possesses little activity towards this compound, is discussed in terms of structure/function. PMID- 1637299 TI - Tyr-143 facilitates interdomain electron transfer in flavocytochrome b2. AB - The role of Tyr-143 in the catalytic cycle of flavocytochrome b2 (L lactate:cytochrome c oxidoreductase) has been examined by replacement of this residue with phenylalanine. The electron-transfer steps in wild-type and mutant flavocytochromes b2 have been investigated by using steady-state and stopped-flow kinetic methods. The most significant effect of the Tyr-143----Phe mutation is a change in the rate-determining step in the reduction of the enzyme. For wild-type enzyme the main rate-determining step is proton abstraction at the C-2 position of lactate, as shown by the 2H kinetic-isotope effect. However, for the mutant enzyme it is clear that the slowest step is interdomain electron transfer between the FMN and haem prosthetic groups. In fact, the rate of haem reduction by lactate, as determined by the stopped-flow method, is decreased by more than 20 fold, from 445 +/- 50 s-1 (25 degrees C, pH 7.5) in the wild-type enzyme to 21 +/ 2 s-1 in the mutant enzyme. Decreases in kinetic-isotope effects seen with [2 2H]lactate for mutant enzyme compared with wild-type, both for flavin reduction (from 8.1 +/- 1.4 to 4.3 +/- 0.8) and for haem reduction (from 6.3 +/- 1.2 to 1.6 +/- 0.5) also provide support for a change in the nature of the rate-determining step. Other kinetic parameters determined by stopped-flow methods and with two external electron acceptors (cytochrome c and ferricyanide) under steady-state conditions are all consistent with this mutation having a dramatic effect on interdomain electron transfer. We conclude that Tyr-143, an active-site residue which lies between the flavodehydrogenase and cytochrome domains of flavocytochrome b2, plays a key role in facilitating electron transfer between FMN and haem groups. PMID- 1637300 TI - A recombinant human 'mini'-hexokinase is catalytically active and regulated by hexose 6-phosphates. AB - Mammalian hexokinase type I is a 100 kDa enzyme that has been considered to be evolved from an ancestral 50 kDa yeast-type hexokinase, insensitive to product inhibition, by gene duplication and fusion. According to this model, and based on many experimental data, the catalytic site is associated with the C-terminal half of the enzyme, although an allosteric site for the binding of glucose 6-phosphate could be present on the N-terminal half of the molecule. We have isolated a cDNA clone of hexokinase from a lambda gt11 human placenta library comprising 2658 bp, containing a single open reading frame of 1893 nucleotides, which encodes a truncate form of hexokinase starting from asparagine-287 to the terminal serine 917. This clone was further digested with restriction enzyme NcoI to obtain almost only the C-terminal half of human hexokinase starting from methionine-455 to the terminal amino acid and was overexpressed in active form in Escherichia coli and purified by ion-exchange h.p.l.c. The overexpressed 'mini'-hexokinase was found not only to catalyse glucose phosphorylation, but also to be inhibited by glucose 6-phosphate and other mono- and bis-phosphate sugars exactly like the complete mammalian enzyme. These results suggest that the C-terminal half of human hexokinase, in addition to the catalytic site, also contains the regulatory site and that the evolutionary relationship between the hexokinases should be reconsidered by including the appearance of a regulatory site before the gene duplication. PMID- 1637301 TI - Chemical heterogeneity as a result of hydroxylamine cleavage of a fusion protein of human insulin-like growth factor I. AB - Recombinant DNA techniques were used to biosynthesize human insulin-like growth factor I (hIGF-I) as a fusion protein wherein the fusion polypeptide is an IgG binding moiety derived from staphylococcal protein A. This fusion protein is produced in Escherichia coli and secreted into the fermentation broth. In order to release mature recombinant-derived hIGF-I (rhIGF-I), the fusion protein is treated with hydroxylamine, which cleaves a susceptible Asn-Gly bond that has been engineered into the fusion protein gene. Reversed-phase h.p.l.c. was used to estimate the purity of the rhIGF-I preparations, especially for the quantification of the methionine sulphoxide-containing variant. It was determined that hydroxylamine cleavage of the fusion protein produced, as a side reaction, hydroxamates of the asparagine and glutamine residues in rhIGF-I. Although isoelectric focusing was effective in detecting, and reversed-phase h.p.l.c. for producing enriched fractions of the hydroxamate variants, ion-exchange chromatography was a more definitive procedure, as it allowed quantification and facile removal of these variants. The identity of the variants as hydroxamates was established by Staphylococcus aureus V8 proteinase digestion, followed by m.s., as the modification was transparent to amino acid and N-terminal sequence analyses. The biological activity of rhIGF-I was established by its ability to incorporate [3H]thymidine into the DNA of BALB/c373 cells and by a radioreceptor assay utilizing human placental membranes. Both assays demonstrate that the native, recombinant and methionine sulphoxide and hydroxamate IGF-I variants are essentially equipotent. PMID- 1637302 TI - Effect of cell-cell and cell-matrix interactions on the response of fibroblasts to epidermal growth factor in vitro. Expression of collagen type I, collagenase, stromelysin and tissue inhibitor of metalloproteinases. AB - Investigations of the effect of epidermal growth factor (EGF) on the expression of four genes involved in the turnover of the extracellular matrix, collagen type I, collagenase, stromelysin and tissue inhibitor of metalloproteinases (TIMP) were performed on four strains of skin fibroblasts in vitro. Addition of EGF to subconfluent cultures for increasing periods of time up to 5 days induced an inhibition of procollagen alpha 1(I) mRNA and a strong stimulation of collagenase (100-fold) and stromelysin (1000-fold) mRNAs, whereas the mRNA of TIMP was increased to a lesser extent (5-fold). After a 40 h pulse with EGF, these effects persisted for 24-48 h after withdrawal of the growth factor and slowly diminished thereafter to attain control values after several days. By culturing fibroblasts for increasing periods of time, different levels of confluence were obtained allowing for the deposition of an extracellular biomatrix. The steady-state level of collagenase and stromelysin mRNAs were profoundly depressed in confluent as against non-confluent cultures, whereas no major change for TIMP and procollagen alpha 1(I) mRNAs was observed. Upon treatment of these cultures with EGF for 48h, the steady-state level of collagenase, stromelysin and TIMP increased, whereas procollagen alpha 1(I) mRNA was slightly reduced. These modifications were, at least in part, dependent upon a regulation of the transcription rate, as suggested from run-off experiments. Similar states of confluence were obtained by seeding cells at increasing densities in short-term cultures in which cell-cell contact predominated. In such culture conditions, the collagenase and stromelysin mRNAs were enhanced in high as compared to low density cultures. The response to EGF was progressively decreased for collagenase, stromelysin and, to a lesser extent, TIMP mRNAs at most densities and a complete lack of response to EGF at the highest cell density was observed. Under all culture conditions the modulation of collagenase mRNA was paralleled by similar modifications of enzyme activity. These results emphasize the importance of the cell-cell contacts and cell-matrix interactions in the expression of the genes coding for metalloproteinases or their inhibitor and their modulation by growth factors. PMID- 1637303 TI - Phosphorylation of the adipose/muscle-type glucose transporter (GLUT4) and its relationship to glucose transport activity. AB - The effects of protein phosphorylation and dephosphorylation on glucose transport activity reconstituted from adipocyte membrane fractions and its relationship to the phosphorylation state of the adipose/muscle-type glucose transporter (GLUT4) were studied. In vitro phosphorylation of membranes in the presence of ATP and protein kinase A produced a stimulation of the reconstituted glucose transport activity in plasma membranes and low-density microsomes (51% and 65% stimulation respectively), provided that the cells had been treated with insulin prior to isolation of the membranes. Conversely, treatment of membrane fractions with alkaline phosphatase produced an inhibition of reconstituted transport activity. However, in vitro phosphorylation catalysed by protein kinase C failed to alter reconstituted glucose transport activity in membrane fractions from both basal and insulin-treated cells. In experiments run under identical conditions, the phosphorylation state of GLUT4 was investigated by immunoprecipitation of glucose transporters from membrane fractions incubated with [32P]ATP and protein kinases A and C. Protein kinase C stimulated a marked phosphate incorporation into GLUT4 in both plasma membranes and low-density microsomes. Protein kinase A, in contrast to its effect on reconstituted glucose transport activity, produced a much smaller phosphorylation of the GLUT4 in plasma membranes than in low-density microsomes. The present data suggest that glucose transport activity can be modified by protein phosphorylation via an insulin-dependent mechanism. However, the phosphorylation of the GLUT4 itself was not correlated with changes in its reconstituted transport activity. PMID- 1637304 TI - Differential effects of platelet-derived growth factor, serum and bombesin on phospholipase D-mediated hydrolysis of phosphatidylethanolamine in NIH 3T3 fibroblasts. AB - In previous studies, activators of protein kinase C, sphingosine, ATP and various oncogenes were each found to enhance phospholipase D-mediated hydrolysis of phosphatidylethanolamine (PtdEtn) in NIH 3T3 fibroblasts. Here I examined possible stimulation of PtdEtn hydrolysis by various growth-stimulatory agents, including serum, bombesin, platelet-derived growth factor (PDGF), fibroblast growth factor (FGF) and insulin. Treatment of NIH 3T3 fibroblasts, prelabelled with [14C]Etn or [32P]PtdEtn, with PDGF-BB resulted in enhanced formation of [14C]Etn or [32P]phosphatidic acid from the respective labelled cellular pools of PtdEtn. A maximal effect (approximately 3-fold stimulation) on PtdEtn hydrolysis was obtained with 50 ng of PDGF/ml after 5 min of treatment. Phosphatidylcholine (PtdCho) was also hydrolysed, although less extensively than PtdEtn, in PDGF stimulated cells. PDGF-stimulate hydrolysis of both PtdEtn and PtdCho was prevented by prolonged (30 h) treatment of cells with 400 nM-phorbol 12-myristate 13-acetate (PMA). Similar to PDGF, fetal calf serum (1-10%) also stimulated PtdEtn hydrolysis. However, in contrast to PDGF, the effect of serum on PtdEtn hydrolysis (i) was not diminished by pretreatment with PMA, and (ii) was synergistic with that of PMA after a 1 h incubation. Compared with PDGF and serum, bombesin had less effect on PtdEtn hydrolysis, while FGF and insulin had no effects at all. In contrast to PDGF or serum, bombesin inhibited the effect of PMA on PtdEtn hydrolysis. PMID- 1637305 TI - The biologically active phospholipid, lysophosphatidic acid, induces phosphatidylcholine breakdown in fibroblasts via activation of phospholipase D. Comparison with the response to endothelin. AB - Lysophosphatidic acid (LPA) is a simple phospholipid that possesses hormone- and growth-factor-like properties. LPA initiates its action by inducing GTP-dependent phosphoinositide hydrolysis and inhibiting adenylate cyclase [van Corven, Groenink, Jalink, Eichholtz & Moolenaar (1989) Cell 59, 45-54]. Here we show that LPA stimulates rapid breakdown of phosphatidylcholine (PC) in Rat-1 fibroblasts. LPA-induced PC breakdown occurs through activation of phospholipase D (PLD), as measured by the formation of free choline and phosphatidic acid and by transphosphatidylation in the presence of butan-1-ol. LPA also stimulates generation of diacylglycerol, but there is no detectable formation of phosphocholine, suggesting that a PC-specific phospholipase C (PLC) is not involved. The response to LPA was compared with that to endothelin, a potent inducer of phospholipid hydrolysis but a poor mitogen for Rat-1 cells. Our results indicate that: (1) LPA is less efficient than endothelin in inducing phosphoinositide and PC breakdown; (2) LPA-induced PLD activation is short-lived, levelling off after 2 min, whereas the endothelin-stimulated increase in PLD activity persists for at least 1 h; (3) the effect of LPA on PLD, like that of endothelin, is blocked by long-term pretreatment of the cells with phorbol ester, suggesting that PLD activation occurs through a protein kinase C-dependent mechanism. Furthermore, our results support the notion that there is no simple causal relationship between the degree of agonist-induced phospholipid hydrolysis and the magnitude of the mitogenic response. PMID- 1637306 TI - Dissociation and unfolding of Pi-class glutathione transferase. Evidence for a monomeric inactive intermediate. AB - The dissociation and unfolding of the homodimeric glutathione transferase (GST) Pi from human placenta, using different physicochemical denaturants, have been investigated at equilibrium. The protein transitions were followed by monitoring loss of activity, intrinsic fluorescence, tyrosine exposure, far-u.v. c.d. and gel-filtration retention time of the protein. At low denaturant concentration (less than 1 M for guanidinium chloride and less than 4.5 M for urea), a reversible dissociation step leading to inactivation of the enzyme was observed. At higher denaturant concentrations the monomer unfolds completely. The same unfolding behaviour was also observed with high hydrostatic pressure as denaturant. Our results indicate that the denaturation of GST Pi is a multistep process, i.e. dissociation of the active dimer into structured inactive monomers followed by unfolding. PMID- 1637307 TI - Epidermal growth factor increases sn-1,2-diacylglycerol levels and activates phospholipase D-catalysed phosphatidylcholine breakdown in Swiss 3T3 cells in the absence of inositol-lipid hydrolysis. AB - Addition of epidermal growth factor (EGF) to quiescent Swiss 3T3 cells resulted in a sustained increase in cellular diacylglycerol (DG) content in the absence of inositol-lipid hydrolysis. In the presence of non-cytotoxic concentrations of butan-1-ol, EGF stimulated the formation of phosphatidylbutanol, indicating that the EGF receptor was able to couple to the activation of phospholipase D (PLD). EGF-stimulated release of choline from Swiss 3T3 cells suggested that the major substrate for this PLD was phosphatidylcholine. Unlike bombesin-stimulated PLD activity, the response to EGF was not inhibited by a selective protein kinase C (PKC) inhibitor (Ro-31-8220), suggesting that it was not dependent on PKC activation. Pre-treatment of Swiss 3T3 cells with the EGF-receptor tyrosine kinase inhibitor AG18 selectively inhibited EGF-stimulated PLD activity; bombesin stimulated PLD activity was unaffected. Butan-1-ol inhibited phorbol ester- and bombesin-stimulated DG formation suggesting a role for a coupled PLD/phosphatidate phosphohydrolase pathway; in contrast, EGF-stimulated DG formation was unaffected. PMID- 1637308 TI - Plasma-membrane-intercalated heparan sulphate proteoglycans in an osteogenic cell line (UMR 106-01 BSP). AB - The heparan sulphate (HS) proteoglycans associated with the cell layer of a rat osteosarcoma cell line [UMR 106-01 (BSP)] were compared with similar cell associated proteoglycans from other cells, and their interaction with the plasma membrane was studied. HS proteoglycans were metabolically labelled by incubation of cell cultures with [3H]glucosamine or [3H]leucine and [35S]sulphate. HS proteoglycan core protein preparation generated by heparitinase digestion of the major species from UMR 106-01 (BSP) cells co-migrated on PAGE with identical preparations from ovarian granulosa cells and parathyroid cells (at approximately 70 kDa). The hydrophobic nature of the major HS proteoglycans from these diverse cell lines, based on elution position from octyl-Sepharose, were also comparable. Linkages of the HS proteoglycan to the cell membrane were investigated by labelling plasma-membrane preparations with a lipid soluble photoactivatable reagent, 3-(trifluoromethyl)-3- (m-[125I]iodophenyl)diazirine (TID), which selectively labels plasma-membrane-spanning peptide domains. Purified HS proteoglycan from UMR 106-01 (BSP) cells was shown to be accessible to the [125I]TID, and the core protein portion of the molecule was labelled, confirming its close association with the plasma membrane. Approx. 36% of 35S-labelled HS proteoglycans were released from the cell surface by phospholipase C (Bacillus thuringiensis), which specifically cleaves phosphatidylinositol-linked proteins. In the presence of insulin, the metabolism of the phospholipase C-sensitive population was unaltered; however, release of the phospholipase C-insensitive population into the medium was increased. These data indicate that a subpopulation of HS proteoglycans are covalently bound to the plasma membrane by a glycosylphosphatidylinositol structure, with the remainder representing those species directly inserted into the plasma membrane via a hydrophobic peptide domain. These observations are similar to those reported for ovarian granulosa cells [Yanagishita & McQuillan (1989) J. Biol. Chem. 264 17551-17558], and thus may represent a general phenomenon for many cell types. PMID- 1637309 TI - Cloning, sequencing and expression in Escherichia coli of the rubredoxin gene from Clostridium pasteurianum. AB - A 3.9 kb BglII-HindIII DNA fragment containing the rubredoxin gene from Clostridium pasteurianum has been cloned using oligonucleotide probes designed from the protein sequence. The 2675 bp SspI-HindIII portion of this fragment has been sequenced and found to contain three open reading frames in addition to the rubredoxin gene. The putative product of one of these open reading frames is similar to various thioredoxin reductases. The rubredoxin gene translates into a sequence that differs from the previously published protein sequence in three positions, D-14, D-22 and E-48 being replaced by the corresponding amides. These changes have been confirmed by partial resequencing of the protein. Promoter-like sequences and a transcription termination signal have been found near the sequence of the rubredoxin gene, which may therefore constitute an independent transcriptional unit. Expression of C. pasteurianum rubredoxin in Escherichia coli strain JM109 has been optimized by subcloning a 476 bp SspI-SspI fragment encompassing the rubredoxin gene. Under these conditions, the latter gene was partly under the control of the lac promoter of pUC18, and the level of rubredoxin production could be increased twofold on addition of a lactose analogue, thus reaching 2-3 mg of pure protein/l of culture. Recombinant rubredoxin was produced in E. coli cells as the holoprotein, and displayed a u.v. visible-absorption spectrum identical with that of the rubredoxin purified from C. pasteurianum. M.s. and N-terminal sequencing showed that C. pasteurianum rubredoxin expressed in E. coli differs from its native counterpart by having an unblocked N-terminal methionine. PMID- 1637310 TI - Neutron and X-ray solution-scattering studies of the ternary complex between proteoglycan-binding region, link protein and hyaluronan. AB - Proteoglycan aggregates of cartilage are stabilized by the formation of a ternary complex between the G1 domain at the N-terminus of the proteoglycan monomer (aggrecan), link protein and hyaluronan polysaccharide. Both the G1 domain and link protein contain similar three-domain structures formed from an immunoglobulin fold and two proteoglycan tandem repeats, the arrangement of which had been investigated by neutron and synchrotron X-ray scattering [Perkins, Nealis, Dunham, Hardingham & Muir (1991) Biochemistry 30, 10708-10716]. Here, solution scattering was used to investigate the ternary complexes formed between a proteolytic fragment of proteoglycan monomer containing G1 (termed binding region), link protein and hyaluronan oligosaccharides containing either 34 or 450 saccharide units (HA34 and HA450). The ternary complex with HA34 had a neutron radius of gyration, RG, at infinite contrast not exceeding 5.5 nm. The ternary complex with HA34 had an X-ray cross-sectional radius of gyration Rxs of 2.4 nm and a neutron Rxs at infinite contrast of 2.00 nm. Since both were similar or larger than the Rxs for binding region (X-rays, 2.04 nm; neutrons, 1.84 nm) and link protein (neutrons, 0.8 nm), analyses showed that the cross-sectional mean width of the ternary complex is greater than those in each of the free proteins, i.e. the two proteins associated side-by-side. Similar results were obtained with HA450 complexed with binding region and with both binding region and link protein. This structural model was verified by hydrodynamic simulations of the experimental sedimentation coefficient of 5.5 S, which showed that a compact ternary-complex structure was formed. Although scattering curve simulations using small spheres were limited for the ternary complex with HA34 because of its approximate RG value, the scattering data were compatible with the formation of a compact complex formed by side-by-side contacts between G1 and link protein. PMID- 1637311 TI - Effects of insulin-like growth factor I on the rates of glucose transport and utilization in rat skeletal muscle in vitro. AB - 1. The effects of insulin-like growth factor I (IGF-I) on the rates of glucose transport and utilization and its interaction with insulin were investigated in rat soleus muscle in vitro. IGF-I increased the rates of glucose transport, lactate formation, glycogen synthesis and the flux of glucose to hexose monophosphate, but it had no effect on the rate of glucose oxidation or glycogenolysis. 2. In the absence of insulin, low levels of IGF-I (0-30 ng/ml) increased the rate of glycolysis and the content of fructose 2,6-bisphosphate, but the content of glucose 6-phosphate remained unaltered; at higher levels of IGF-I (300-3000 ng/ml) the rate of glycolysis and the content of fructose 2,6 bisphosphate showed a further modest increase, but the content of glucose 6 phosphate doubled. Similar changes were seen when the level of insulin was increased from basal (0-0.4 ng/ml) to maximal (40 ng/ml). 3. Neither IGF-I nor insulin affected the contents of ATP, ADP, AMP, phosphocreatine or citrate. 4. Maximal concentrations of IGF-I increased the rate of lactate formation to a greater extent than did maximal concentrations of insulin. 5. In the presence of IGF-I, the rate of glucose utilization was less responsive to insulin. 6. The results suggest that, in rat skeletal muscle: (a) IGF-I increases the rates of glucose transport and utilization independently of insulin, and has a preferential effect on the rate of lactate formation; (b) the effects of IGF-I and insulin are not additive; (c) in addition to its effects on glucose transport, IGF-I increases the rate of glycogen synthesis and may stimulate glycolysis at the level of 6-phosphofructokinase; (d) changes in the content of fructose 2,6-bisphosphate may be part of the mechanism to regulate glycolytic flux in skeletal muscle in response to either IGF-I or insulin. PMID- 1637312 TI - Separation and characterization of the two Asn-linked glycosylation sites of chicken serum riboflavin-binding protein. Glycosylation differences despite similarity of primary structure. AB - Serum riboflavin-binding protein, a phosphoglycoprotein from the blood of laying hens, contains two Asn-Xaa-(Thr)Ser sequons in very similar but well-separated regions of amino acid sequence. In order to evaluate the effect of local amino acid sequence on the structure of the attached oligosaccharides, serum riboflavin binding protein was purified to homogeneity, reduced and alkylated, digested with trypsin, and the two glycopeptides were separated by reversed-phase chromatography. After digestion with peptide-N-glycosidase F the released oligosaccharides were separated by high-pH anion-exchange chromatography and the oligosaccharide profiles of the two glycopeptides were compared. Although the two asparagine residues that are glycosylated are contained in pentapeptide segments in which four out of five amino acids are identical, the array of oligosaccharides present at each site show differences in both type and distribution. This suggests that local secondary or tertiary structure, or the order of glycosylation, influences the oligosaccharide structure more than does the primary structure flanking the attachment site. PMID- 1637313 TI - A serine proteinase of an archaebacterium, Halobacterium mediterranei. A homologue of eubacterial subtilisins. AB - A homogeneous serine proteinase secreted by the extreme halophilic bacterium Halobacterium mediterranei 1538 was isolated by affinity chromatography on bacitracin-Sepharose with a yield of 48% (260-fold purification). The enzyme reveals an optimum for pyroglutamyl-Ala-Ala-Leu p-nitroanilide hydrolysis at pH 8.0-8.5 (Km 0.14 mM; k(cat). 36.9 s-1). Its activity increases linearly with NaCl concentration over the range 2-5 M. The substrate specificity of the enzyme is comparable with that of secretory subtilisins, the extent of protein degradation approaching that attained with proteinase K. The enzyme has a molecular mass of 41 kDa and a pI of 7.5. The N-terminal sequence of H. mediterranei serine proteinase reveals a 50% identity with that of Thermoactinomyces vulgaris serine proteinases, indicating that the enzyme belongs to the subtilisin family. Hence the serine proteinase secreted by the halophilic bacterium should be considered as a functional analogue, and a structural homologue, of eubacterial serine proteinases (subtilisins). PMID- 1637314 TI - Structural analysis of the regulatory elements of the type-II procollagen gene. Conservation of promoter and first intron sequences between human and mouse. AB - Transcription of the type-II procollagen gene (COL2A1) is very specifically restricted to a limited number of tissues, particularly cartilages. In order to identify transcription-control motifs we have sequenced the promoter region and the first intron of the human and mouse COL2A1 genes. With the assumption that these motifs should be well conserved during evolution, we have searched for potential elements important for the tissue-specific transcription of the COL2A1 gene by aligning the two sequences with each other and with the available rat type-II procollagen sequence for the promoter. With this approach we could identify specific evolutionarily well-conserved motifs in the promoter area. On the other hand, several suggested regulatory elements in the promoter region did not show evolutionary conservation. In the middle of the first intron we found a cluster of well-conserved transcription-control elements and we conclude that these conserved motifs most probably possess a significant function in the control of the tissue-specific transcription of the COL2A1 gene. We also describe locations of additional, highly conserved nucleotide stretches, which are good candidate regions in the search for binding sites of yet-uncharacterized cartilage-specific transcription regulators of the COL2A1 gene. PMID- 1637315 TI - Iron release and membrane damage in erythrocytes exposed to oxidizing agents, phenylhydrazine, divicine and isouramil. AB - Mouse erythrocytes were incubated with oxidizing agents, phenylhydrazine, divicine and isouramil. With all the oxidants a rapid release of iron in a desferrioxamine (DFO)-chelatable form was seen and it was accompanied by methaemoglobin formation. If the erythrocytes were depleted of GSH by a short preincubation with diethyl maleate, the release of iron was accompanied by lipid peroxidation and, subsequently, haemolysis. GSH depletion by itself did not induce iron release, methaemoglobin formation, lipid peroxidation or haemolysis. Rather, the fate of the cell in which iron is released depended on the intracellular availability of GSH. In addition, iron release was higher in depleted cells than in native ones, suggesting a role for GSH in preventing iron release when oxidative stress is imposed by the oxidants. Iron release preceded lipid peroxidation. The latter was prevented when the erythrocytes were preloaded with DFO in such a way (preincubation with 10 mM-DFO) that the intracellular concentration was equivalent to that of the released iron, but not when the intracellular DFO was lower (preincubation with 0.1 mM-DFO). Extracellular DFO did not affect lipid peroxidation and haemolysis, suggesting again that the observed events occur intracellularly (intracellular chelation of released iron). The relevance of iron release from iron complexes in the mechanisms of cellular damage induced by oxidative stress is discussed. PMID- 1637316 TI - Modification of catalytically important carboxy residues in endoglucanase D from Clostridium thermocellum. AB - Endoglucanase D (EC 3.2.1.4; EGD) from Clostridium thermocellum is rapidly (k = 216 M-1.min-1) and almost completely (greater than 95%) inactivated with Woodward's reagent K (N-ethyl-5-phenylisoxazolium-3'-sulphonate). Spectrophotometric analysis at 340 nm reveals that eight carboxy residues react, whereas specific ligands protect one residue against modification. The enzyme retains it full activity under the latter conditions. The kinetics and pH dependence of inactivation point towards the involvement of one or more essential carboxy groups with a pKa of 5.7-5.8. Samples modified in the absence or presence of ligand were analysed by reversed-phase liquid chromatography after proteolysis with subtilisin. Dual-wavelength monitoring at 214 and 340 nm during this fractionation leads to the identification of a putatively active-site peptide (Gly-508-Ala-562) which was further characterized by amino acid and partial N terminal sequence analyses. Asp-546 and Glu-555 are postulated as possible active site residues. This follows from alignments using ten endoglucanase sequences belonging to the same family. Strong local conservation suggests that this C terminal sequence is structurally and/or functionally important. PMID- 1637317 TI - Phosphorylation of the spliced variant forms of the recombinant stimulatory guanine-nucleotide-binding regulatory protein (Gs alpha) by protein kinase C. AB - Recombinant forms of Gs alpha-1 and Gs alpha-4 were shown to act as substrates for a purified preparation of brain protein kinase C. Both forms of Gs alpha were thermally denatured during the incubation such that phosphorylation was virtually complete (greater than 90%) after 30 min. The quantity of phosphate incorporated into approximately equivalent starting amounts of the two forms of Gs alpha (4.8 pmol of Gs alpha-1 and 5.5 pmol of Gs alpha-4) at maximal phosphorylation were 0.23 +/- 0.08 pmol for Gs alpha-1 and 0.56 +/- 0.12 pmol for Gs alpha-4. Since both forms of Gs alpha were thermally denatured to the same extent after 30 min, the increased phosphorylation state of Gs alpha-4 provides evidence that Gs alpha 4 contains an additional phosphorylation site. Bray and co-workers [Bray, Carter, Simmons, Guo, Puckett, Kamhollz, Spiegel & Nirenberg (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 8893-8897] proposed that an additional phosphorylation site may exist at the splice junction in Gs alpha-4. The guanine-nucleotide-free form of Gs alpha appears to be the preferred substrate for phosphorylation. This interpretation is based upon the following observations. (i) Guanosine 5'-[beta thio]diphosphate at micromolar concentrations inhibits the susceptibility of Gs alpha to phosphorylation; (ii) beta gamma-subunits, which inhibit GDP release from Gs alpha-GDP at millimolar Mg2+ concentrations, also inhibit the susceptibility of Gs alpha to phosphorylation; and (iii) guanosine 5'[beta gamma imido]triphosphate inhibits the susceptibility of Gs alpha to act as a substrate for phosphorylation. These studies suggest that there is potential for cross-talk between receptors which trigger PtdIns(4,5)P2 hydrolysis and subsequently protein kinase C activation, and receptors which stimulate adenylate cyclase via Gs. PMID- 1637318 TI - Glutamine transport and metabolism in mammalian skeletal muscle. PMID- 1637319 TI - Some evidence for the existence of substrate cycles and their utility in vivo. PMID- 1637320 TI - Agonist-evoked Ca2+ entry in human platelets. PMID- 1637321 TI - Molecular cloning and expression of a new rat liver cell-CAM105 isoform. Differential phosphorylation of isoforms. AB - An hepatocyte cell-adhesion molecule (cell-CAM105) was recently shown to be identical with the liver plasma-membrane ecto-ATPase. This protein has structural features of the immunoglobulin superfamily and is homologous with carcinoembryonic antigen proteins. We have cloned a cDNA encoding a new form of the cell-CAM105 which is a variant of the previously isolated clone. In addition to having a shorter cytoplasmic domain, the new isoform also has substitutions clustered in the first 130 amino acids of the extracellular domain. Both of these isoforms are expressed on the surface of hepatocytes with the shorter variant being the predominant form. The previously isolated cell-CAM105 (long form) has more potential phosphorylation sites than does the new isoform (short form). Both isoforms are found to be phosphorylated after incubation with [32P]phosphate in vitro, with the long form being phosphorylated to a significantly higher extent. This observed differential phosphorylation could be one of the mechanisms for the regulation of isoform functions. Using antipeptide antibodies specific for the long form and antibodies that are reactive with both isoforms, we have shown that both isoforms are localized in the canalicular domain of hepatocytes. The sequence differences between these two isoforms suggest that they are probably derived from different genes rather than from alternative splicing. PMID- 1637322 TI - Localization of intestinal trefoil-factor mRNA in rat stomach and intestine by hybridization in situ. AB - A cDNA encoding rat intestinal trefoil factor (rITF) was prepared by reverse transcription and PCR amplification. The sequence obtained was well conserved with that of other trefoil peptides. An antisense riboprobe produced from the clone was used to localize the sites of ITF expression in the rat gastrointestinal tract using hybridization in situ. We found rITF mRNA in goblet cells in the small intestine and colon; a gradient of signal strength greatest near the crypt base was sometimes present. We found no evidence for rITF expression in Brunner's glands, the pancreas, or most regions of the gastric mucosa. Surprisingly, strong signals for rITF mRNA were detected in a region of stomach at the junction of the squamous fore-stomach with the glandular gastric mucosa. This region, which may correspond to the cardiac region, formed part of a larger area of cells staining positive for acid mucins. We hypothesize that concerted expression occurs of particular trefoil peptides with specific mucins, and that this organization reflects a functional relationship between mucins and trefoil peptides. PMID- 1637323 TI - A simple, fast, one-step method for the purification of the skeletal-muscle ryanodine receptor. AB - In this paper we describe a simple, fast, one-step method for the purification of the skeletal-muscle ryanodine receptor. The ryanodine receptor from CHAPS solubilized junctional sarcoplasmic-reticulum membranes was adsorbed to a spermine-agarose column and eluted by 2 mM-spermine. The purified receptor, consisting predominantly of a 450 kDa polypeptide on SDS/PAGE, binds [3H]ryanodine with a specific activity of approximately 300 pmol/mg of protein and with a high affinity (KD = 4.7 +/- 2 nM). The purified receptor appears to retain the pharmacological properties of the receptor in the original membranes. The purification resulted in over 80% recovery of the initial ryanodine-binding sites and about 30-96-fold purification. This simple and fast method is highly reproducible and suitable for purification of small as well as large quantities of ryanodine receptor. PMID- 1637324 TI - A choice between glycogen and delta-crystallin accumulation is made in glial cells and not influenced by overlying neurons. AB - Chick-embryo neuroretinal cells convert extensively into lens under low-glucose conditions, but this transdifferentiation process is blocked by high-glucose media. We have previously observed an inverse relationship between the levels of glycogen (a marker of normal retinoglial differentiation) and of delta-crystallin (a lens marker) in such cultures. However, most of the glycogen accumulated under high-glucose conditions is apparently localized in those glial (G) cells underlying clusters of neurons (N cells). We here show that glial-enriched cultures (largely depleted of N cells) both accumulate glycogen and fail to transdifferentiate in high-glucose media. Moreover, glycogen localization in groups of glial cells is unaffected by the absence of N cells. Thus the choice between normal and foreign differentiation pathways is made autonomously within the retinoglial-cell population and is not influenced significantly by the presence or absence of N cells. PMID- 1637325 TI - Surface topography of histidine residues of tetanus toxin probed by immobilized metal-ion affinity chromatography. AB - Tetanus toxin contains 14 histidine residues: six of them are localized in the light chain (L), one is present in the N-terminal half of the heavy chain (HN) and the remaining seven histidines are localized in the C-terminal half of the heavy chain (Hc). Using immobilized-metal-ion affinity chromatography with Chelating Superose-Zn(II), we show that histidines of Hc are exposed to the protein surface and are responsible for the binding of tetanus toxin and of Hc to the immobilized metal. The histidines of the L chain are not available for co ordination of matrix-bound Zn2+; however, two of them and three of the histidines of fragment Hc are accessible to diethyl pyrocarbonate. Chromatography on Superose-Zn(II) is also shown to be a simple and efficient method for the rapid isolation of tetanus toxin and of its Hc fragment, which can be extended to the botulinum neurotoxins. PMID- 1637326 TI - Instability of the protoplast membrane of facultative alkaliphilic Bacillus sp. C 125 at alkaline pH values below the pH optimum for growth. AB - Cell walls of facultative alkaliphilic Bacillus sp. C-125 consist of three polymers (peptidoglycan, teichuronopeptide and teichuronic acid). Protoplasts prepared from the strain with egg-white lysozyme regenerated cell walls at neutral pH, but not at pH above 8.5. The protoplasts were susceptible to lysis at alkaline pH. The protoplasts exposed to alkaline pH rapidly burst and lost ability to regenerate their cell walls. The alkali-instability was similar to that of protoplasts from neutrophilic Bacillus subtilis 168. The membrane vesicles were also labile at alkaline pH. The acidic wall components of strain C 125 may contribute to stabilization of the cytoplasmic membrane of cells growing at alkaline pH, probably by shielding the membrane from direct exposure to an alkaline environment. PMID- 1637328 TI - Reverse vesicles as a new system for studying enzymes in organic solvents. AB - A new approach to the study of enzyme activity in organic solvents has been developed by using optically transparent reverse vesicles. Polyphenol oxidase was incorporated in an active form into the above ternary system formed by the non ionic surfactant tetra(ethylene glycol) dodecyl ether/n-dodecane/water. The enzyme in this microenvironment, surprisingly, showed an apparent positive co operativity which has never before been described either in aqueous solution or in reverse micelles. In addition, the Vmax. expressed was similar to that in water and twice that displayed in reverse micelles. PMID- 1637329 TI - Contribution of five amino acid residues in the glutathione-binding site to the function of human glutathione transferase P1-1. AB - Five amino acids in proximity to GSH bound in the active-site cavity of human Class Pi glutathione transferase (GST) P1-1 were mutated by oligonucleotide directed site-specific mutagenesis. The following mutations gave catalytically active mutant proteins with the proper dimeric structure: Arg14----Ala, Lys45--- Ala, Gln52----Ala, Gln65----His and Asp99----Asn. The mutation Gln65----Ala was also made, but the protein was not characterized because of its poor catalytic activity. Residues Arg14, Lys45, Gln52 and Gln65 all contribute to binding of glutathione, and the substitutions caused an approx. 10-fold decrease in affinity, corresponding to 5 kJ/mol, except for Arg14, for which the effect was larger. In addition, Arg14 appears to have an important structure role, since the Arg14----Ala mutant demonstrated a significantly lower stability as compared with the wild-type and the other mutant enzymes. Asp99 primarily contributes to catalysis rather than to binding. The kcat./Km-versus-pH profile for the Asp99--- Asn mutant is shifted by 0.5 pH unit in the alkaline direction, and it is proposed that Asp99 may participate in proton transfer in the catalytic mechanism. The possibility of redesigning the substrate specificity for GSTs was shown by the fact that the mutant Lys45----Ala displayed a higher catalytic efficiency with GSH monoethyl ester than with its natural substrate, GSH. PMID- 1637330 TI - Reconstitution in vitro of a membrane-fusion event involved in constitutive exocytosis. A role for cytosolic proteins and a GTP-binding protein, but not for Ca2+. AB - The fusion of post-Golgi transport vesicles with the plasma membrane is perhaps the least well understood step in the network of intracellular membrane traffic. We have used an 'in vitro' system to study this membrane-fusion event. We show here that fusion requires the presence of cytosolic proteins, but not Ca2+, and is inhibited by the non-hydrolysable GTP analogue guanosine 5'-[gamma thio]triphosphate, which indicates the involvement of a GTP-binding protein. PMID- 1637327 TI - 5'-Nucleotidase: molecular structure and functional aspects. PMID- 1637331 TI - Structure determination of a novel cyclic phosphocompound isolated from Desulfovibrio desulfuricans. AB - The structure of a novel diphosphodiester compound recently detected in Desulfovibrio desulfuricans cells [Santos, Fareleira, Pedregal, LeGall & Xavier (1991) Eur. J. Biochem. 201, 283-287] was fully elucidated using a combination of n.m.r. techniques in aqueous and in methanolic solutions. The novel metabolite was identified as 3-methyl-1,2,3,4-tetrahydroxybutane-1,3-cyclic bisphosphate, and the minimum energy conformation is presented. The two chiral centres have the relative configuration RS. PMID- 1637332 TI - A member of the eukaryotic subtilisin family (PC3) has the enzymic properties of the type 1 proinsulin-converting endopeptidase. AB - PC3, a mammalian homologue of the yeast subtilisin-like proteinase Kex2, was expressed in Xenopus oocytes and its activity was characterized. PC3 cleaved human proinsulin at one of the two dibasic sites (KTRR32 but not LQKR65). The specificity, inhibitor profile, pH optimum (5.5) and Ca(2+)-dependence (K0.5 = 2.5-3 mM) paralleled those of the insulin-granule type 1 endopeptidase activity, suggesting a role for PC3 in the conversion of prohormones. PMID- 1637333 TI - Activation of phospholipase D by alpha-thrombin or epidermal growth factor contributes to the formation of phosphatidic acid, but not to observed increases in 1,2-diacylglycerol. AB - The receptor-mediated activation of a phosphatidylcholine-hydrolysing phospholipase D (PLD) has recently been described. We investigated the effect of alpha-thrombin and epidermal growth factor (EGF) on cellular PLD activity in order to determine the role of this enzyme in mitogen-induced increases in phosphatidic acid and sn-1,2-diacylglycerol. In the presence of ethanol, stimulation of [3H]myristic acid-labelled quiescent IIC9 cells with alpha thrombin or EGF resulted in a rapid increase in radiolabelled phosphatidyl ethanol which reached a plateau at 1 min, indicating the rapid and transient activation of PLD. We observed a concomitant decrease in the mitogen-stimulated increase of radiolabelled phosphatidic acid. In contrast, ethanol did not significantly effect the elevation of sn-1,2-diacylglycerol levels stimulated by alpha-thrombin or EGF as determined by measurement of sn-1,2-diacylglycerol mass or the appearance of [3H]1,2-diacylglycerol. A novel lipid, detected by two dimensional t.l.c. analysis, was generated in [3H]myristic acid-labelled cells stimulated with alpha-thrombin, but not EGF, in the presence of ethanol. Treatment in vitro of cellular lipids isolated from [3H]myristic acid-labelled cultures with PLD in the presence of ethanol also resulted in the generation of this novel lipid species, supporting the role of this enzyme in its production. These data indicate that in quiescent IIC9 cells: (a) alpha-thrombin or EGF rapidly and transiently activates a PLD; (b) although this activation is responsible for part of the mitogen-induced increases in phosphatidic acid, it does not contribute to induced increases in sn-1,2-diacylglycerol; and (c) activation of this enzyme appears to be involved in the formation of a novel lipid generated in response to alpha-thrombin, but not EGF, in IIC9 fibroblasts. PMID- 1637334 TI - Relationship between glutathione content in liver and glutathione conjugation rate in the rat in vivo. Effect of buthionine sulphoximine pretreatment on conjugation of the two 2-bromoisovalerylurea enantiomers during intravenous infusion. AB - The relationship between hepatic glutathione content and hepatic glutathione conjugation rate in the rat in vivo was investigated. As substrate for glutathione conjugation, racemic (R,S)-2-bromoisovalerylurea (BIU) was used which gives rise to the biliary excretion of two diastereoisomeric glutathione conjugates and the urinary excretion of two diastereoisomeric mercapturates. The excretion rate of the glutathione conjugate in bile reflects hepatic conjugation exclusively. An intravenous infusion of BIU was given and the excretion rates of the metabolites in bile and urine were determined. The glutathione concentration in the liver was followed by taking biopsies every hour. Glutathione was depleted by the infused substrate; in rats that were pretreated with the inhibitor of glutathione biosynthesis, buthionine sulphoximine (BSO), the depletion of the glutathione content was more rapid. The rate of excretion of the glutathione conjugate in bile was plotted against hepatic glutathione content. These results indicate that the 'organ Km' for glutathione in the liver is approximately 0.5 mumol/g of liver, so that the hepatic glutathione conjugation rate is decreased only at severe glutathione depletion. PMID- 1637335 TI - Human tumour cathepsin B. Comparison with normal liver cathepsin B. AB - Cathepsin B was purified from normal human liver and several human tumour tissues and partially characterized. Three forms of cathepsin B, with molecular masses of 25 kDa, 26 kDa (the two appearing as a doublet) and 30 kDa, were detected in SDS/polyacrylamide gels. The 25-26 kDa doublet was associated with the fractions from tumours and normal liver containing the highest cathepsin B activity. Cathepsin B from both sources showed similar pH optima. Both normal liver and tumour cathepsin B exhibited similar kinetics against selected synthetic substrates. At neutral pH and 24 degrees C, cathepsin B from both normal liver and tumour exhibited a lower Km and a higher kcat./Km than at pH 6.0. Their inhibitory profiles against synthetic inhibitors were also similar. Immunological studies with a monospecific antibody against the mature double-chain form of human liver cathepsin B and an antibody against a cathepsin B-derived synthetic peptide established the immunological similarity of liver and tumour enzymes. The N-terminal sequences of the 25 kDa and 26 kDa forms were identical with that of the heavy chain of the mature double-chain form of human cathepsin B, whereas the N-terminal sequence of the 30 kDa species was identical with that of the single chain form of human cathepsin B. Treatment of the double-chain form of cathepsin B from normal liver and tumours with the endoglycosidase peptide-N4-(N-acetyl beta-glucosaminyl)asparagine amidase converted the 26 kDa form into 25 kDa in SDS/polyacrylamide gels, suggesting that cathepsin B may exist as both glycosylated and unglycosylated forms. Our results, in contrast with those reported earlier for mouse cathepsin B, indicate that human liver and tumour cathepsin B are similar. PMID- 1637336 TI - Regulation of pyruvate dehydrogenase by insulin and polyamines within electropermeabilized fat-cells and isolated mitochondria. AB - 1. Regulation of the mammalian pyruvate dehydrogenase (PDH) complex by insulin and polyamines has been examined by using electropermeabilized rat epididymal fat cells and isolated mitochondria. The complex could be regulated within the permeabilized cells not only by insulin, but also by certain low-M(r) species, including Ca2+ and the polyamine spermidine. 2. Both spermine and spermidine increased the level of active dephosphorylated PDH (PDHa) in isolated adipose tissue mitochondria 2-3-fold, with half-maximal effects at 0.9 mM and 1.7 mM respectively. By contrast, PDH activity in rat heart mitochondria was essentially insensitive to the effects of these polyamines. 3. The effects on PDH activity of incubation of adipose-tissue mitochondria with spermine persisted through re isolation and re-incubation of the mitochondria in the absence of the polyamine. 4. No evidence was found of any increase in the concentration of spermine associated with purified mitochondrial fractions prepared from insulin-treated tissue. 5. Overall, the data provide further evidence against a role for polyamines in the rapid stimulation of PDH by insulin, but suggest that polyamines may be important in mediating longer-term changes in the activity of the complex. PMID- 1637337 TI - Evidence for G proteins in rat parotid plasma membranes and secretory granule membranes. AB - G proteins were identified in rat parotid plasma membrane-enriched fractions and in two populations of isolated secretory granule membrane fractions. Both [32P]ADP-ribosylation analysis with bacterial toxins and immunoblot analysis with crude and affinity-purified antisera specific for alpha subunits of G proteins were utilized. Pertussis toxin catalysed the ADP-ribosylation of a 41 kDa substrate in the plasma membrane fraction and both secretory granule membrane fractions. Cholera toxin catalysed the ADP-ribosylation of two substrates with molecular masses of 44 kDa and 48 kDa in the plasma membrane fraction but not in the secretory granule fractions. However, these substrates were detected in the secretory granule fractions when recombinant ADP-ribosylating factor was present in the assay medium. Immunoblot analysis of rat parotid membrane fractions using both affinity-purified and crude antisera revealed strong immunoreactivity of these membranes with anti-Gs alpha, -Gi alpha 1/alpha 2 and -Gi alpha 3 sera. In contrast Gs alpha was the major substrate found in both of the secretory granule fractions. Granule membrane fractions also reacted moderately with anti-Gi alpha 3 antiserum, and weakly with anti-Gi alpha 1/alpha 2 and -G(o) alpha sera. The results demonstrate that the parotid gland membranes express a number of G proteins. The presence of G proteins in secretory granule membranes suggests that they may play a direct role in regulating exocytosis in exocrine glands. PMID- 1637338 TI - A potentiometric titration study of the interaction of heparin with metal cations. AB - Potentiometric titrations, at ionic strengths (I) ranging from 0.0057 to 0.336, suggest that Ca2+, Cu2+, Li+ and Na+ bind to heparin in a manner that depends on cation identity. These interactions were less affected by the value of I than those of heparin with Mg2+, which binds weakly below I0.050 and with K+, which binds weakly at I0.0057. Of the interactions studied, that of heparin with Cu2+ was the least readily reversible. PMID- 1637339 TI - Additional biochemical findings in a patient and fetal sibling with a genetic defect in the sphingolipid activator protein (SAP) precursor, prosaposin. Evidence for a deficiency in SAP-1 and for a normal lysosomal neuraminidase. AB - It has been shown that sphingolipid activator proteins (SAPs) 1 and 2 are encoded on the same gene along with two other putative activator proteins [Furst, Machleidt & Sandhoff (1988) Biol. Chem. Hoppe-Seyler 369, 317-328 and O'Brien, Kretz, Dewji, Wenger, Esch & Fluharty (1988) Science 241, 1098-1101]. We have undertaken further biochemical investigations on a patient and fetal sibling, who were previously shown to have a unique sphingolipid storage disorder associated with an SAP-2 deficiency [Harzer, Paton, Poulos, Kustermann-Kuhn, Roggendorf, Grisar & Popp (1989) Eur. J. Pediatr. 149, 31-39]. The severity of their disorder suggested that other products of the SAP precursor or prosaposin gene may also be deficient. The turnover of cerebroside sulphate and globotriaosylceramide were investigated and were both impaired in fibroblasts from the patient and fetus. However, the activities of cerebroside sulphate sulphatase and globotriaosylceramide alpha-galactosidase in vitro were normal in cells from the fetus and patient respectively. In addition, there was an increase in cerebroside sulphate concentration in the kidney of the affected fetus. These results indicate that, in addition to the SAP-2 deficiency, there was a defect in SAP-1 function in this disorder. Additional increases in the concentration of monohexosyl- and dihexosyl-ceramide in the fetal kidney probably reflect the deficiency of SAP-2 in the case of monohexosylceramides, and the combined activator deficiency in the case of dihexosylceramides. Lactosylceramide-loading studies confirmed that there was a defect in the turnover of this lipid in fibroblasts from the affected patient and fetus but not from a patient with an isolated SAP-1 deficiency, or from patients with Krabbe disease, GM1 gangliosidosis or galactosialidosis. It has been suggested [Potier, Lamontagne, Michaud & Tranchemontagne (1990) Biochem. Biophys. Res. Commun. 173, 449-456] that the prosaposin gene also codes for lysosomal neuroaminidase. However, we found normal neuraminidase activity in fibroblasts from our patient, using assay conditions which are diagnostic for sialidosis patients. The role of prosaposin gene products in sphingolipid metabolism is discussed in view of our biochemical findings in this genetic disorder. PMID- 1637340 TI - Active-site characterization of S1 nuclease. I. Affinity purification and influence of amino-group modification. AB - A simple procedure, involving heat-treatment, DEAE-Sephadex, AMP-Sepharose and Bio-Gel P-60 chromatography, was developed for the purification of S1 nuclease to homogeneity from commercially available Takadiastase powder. Chemical modification of the amino groups of purified S1 nuclease revealed that lysine is essential for single-stranded DNAase, RNAase and phosphomonoesterase activities associated with the enzyme. The kinetics of inactivation suggested the involvement of a single lysine residue in the active site of the enzyme. Additionally, lysine modification was accompanied by a concomitant loss of all the activities of the enzyme, indicating the presence of a common catalytic site responsible for the hydrolysis of single-stranded DNA, RNA and 3'-AMP. Substrate protection and inhibitor-binding studies on enzyme modified with 2,4,6 trinitrobenzenesulphonic acid showed that lysine may be involved in the substrate binding. PMID- 1637341 TI - Inhibition of cysteine proteinases in lysosomes and whole cells. AB - Inhibitors of cysteine proteinases have been used extensively to dissect the roles of these proteinases in cells. Surprisingly though, little work has been performed to demonstrate unequivocally that the inhibitors reach and inactivate their target proteinases in cell culture or in vivo. In the present study, the permeability of lysosomes and whole cells has been studied. Benzyloxycarbonyl (Z) [125I]iodo-Tyr-Ala-diazomethane (CHN2), an inhibitor of cathepsins L and B, has been shown to label active forms of these enzymes in lysosomes and whole cells. The ability of other cysteine proteinase inhibitors to block this labelling has been used to indicate the permeation of these compounds. All the inhibitors were able to block labelling by Z-[125I]iodo-Tyr-Ala-CHN2 in lysosomal extracts. In intact lysosomes or cells, however, only N-[N-(L-3-trans-ethoxycarbonyloxirane-2 carbonyl)-L-leucyl]-3- methylbutylamine ('E-64d') Z-Tyr-Ala-CHN2, Z-Phe-Ala-CHN2 and Z-Phe-Phe-CHN2 were able to block labelling by Z-[125I]iodo-Tyr-Ala-CHN2. N [N-(L-3-trans-Carboxyoxirane-2-carbonyl)-L-leucyl]amino-4-gua nidinobutane (E-64) and leupeptin were unable to block labelling by Z-[125I]iodo-Tyr-Ala-CHN2 in lysosomes or in cells. The ability to block labelling in lysosomes is an indication of the ability of the inhibitor to diffuse across membranes. Thus E-64 and leupeptin do not readily permeate membranes and therefore their uptake into cells probably only occurs via pinocytosis. PMID- 1637342 TI - Use of rosy mutant strains of Drosophila melanogaster to probe the structure and function of xanthine dehydrogenase. AB - The usefulness in structure/function studies of molybdenum-containing hydroxylases in work with rosy mutant strains of Drosophila melanogaster has been investigated. At least 23 such strains are available, each corresponding to a single known amino acid change in the xanthine dehydrogenase sequence. Sequence comparisons permit identification, with some certainty, of regions associated with the iron-sulphur centres and the pterin molybdenum cofactor of the enzyme. Procedures have been developed and rigorously tested for the assay in gel filtered extracts of the flies, of different catalytic activities of xanthine dehydrogenase by the use of various oxidizing and reducing substrates. These methods have been applied to 11 different rosy mutant strains that map to different regions of the sequence. All the mutations studied cause characteristic activity changes in the enzyme. In general these are consistent with the accepted assignment of the cofactors to the different domains and with the known reactivities of the molybdenum, flavin and iron-sulphur centres. Most results are interpretable in terms of the mutation affecting electron transfer to or from one redox centre only. The activity data provide evidence that FAD and the NAD+/NADH binding sites are retained in mutants mapping to the flavin domain. Therefore, despite some indications from sequence comparisons, it is concluded that the structure of this domain of xanthine dehydrogenase cannot be directly related to that of other flavoproteins for which structural data are available. The data also indicate that the artificial electron acceptor phenazine methosulphate acts at the iron-sulphur centres and suggest that these centres may not be essential for electron transfer between molybdenum and flavin. The work emphasizes the importance of combined genetic and biochemical study of rosy mutant xanthine dehydrogenase variants in probing the structure and function of enzymes of this class. PMID- 1637343 TI - Participation of the phenolic hydroxyl group of Tyr-8 in the catalytic mechanism of human glutathione transferase P1-1. AB - The coding region of cDNA corresponding to human class Pi glutathione transferase P1-1 was amplified by the PCR, subcloned into an expression vector, pKHP1, expressed in Escherichia coli, and characterized. The physicochemical and catalytic properties of recombinant glutathione transferase P1-1 were indistinguishable from those of the enzyme previously isolated from human placenta. The active-site residue Tyr-8 of the wild-type enzyme was converted into Phe by means of oligonucleotide-directed mutagenesis. The mutant enzyme Y8F displayed a 300-fold decrease in specific activity, ascribable mainly to a lowered k(cat.) (or V) value. Kinetic parameters reflecting binding affinity, S0.5 (substrate concn. giving 1/2V) and I50 (concn. of inhibitor giving 50% remaining activity), were only moderately elevated in the mutant enzyme. These results indicate that Tyr-8 contributes primarily to catalysis as such, rather than to binding of the substrates. The dependence of k(cat.)/Km on pH shows an optimum at pH 7.0, defined by acidic and basic ionic dissociation constants with pKa1 = 6.7 and pKa2 = 7.3 respectively. The mutant enzyme Y8F does not display the basic limb of the k(cat.)/Km versus pH profile, but shows a monotonic increase of k(cat.)/Km with an apparent pKa1 of 7.1. The results indicate that the phenolic hydroxyl group of Tyr-8 in un-ionized form, but not the phenolate of Tyr-8, contributes to catalysis by glutathione transferase P1-1. PMID- 1637344 TI - Evidence for phosphatidylinositol hydrolysis in pancreatic islets stimulated with carbamoylcholine. Kinetic analysis of inositol polyphosphate metabolism. AB - Anion-exchange h.p.l.c. was used initially to analyse the products formed after addition of either [3H]Ins(1,3,4,5)P4 or [3H]Ins(1,4,5)P3 to homogenates of pancreatic islets. Metabolic routes similar to those of other tissues were established: dephosphorylation of Ins(1,4,5)P3 to Ins(1,4)P2 and then Ins4P; and sequential degradation of Ins(1,3,4,5)P4 to Ins(1,3,4)P3, Ins(3,4)P2 and Ins(3 or 1)P. In addition, there was a limited conversion of Ins(1,3,4)P3 into Ins(1,3)P2. After stimulation of [3H]inositol-prelabelled islets with the muscarinic-receptor agonist carbamoylcholine (carbachol), there was a rapid (10 s) increase in Ins(1,4,5)P3, Ins(1,3,4)P3, Ins(1,4)P2 and Ins4P. In the presence of 10 mM-LiCl, Ins1P was also significantly increased (P less than 0.05) by 5 s, before any increase in Ins4P (10 s), Ins(1,3)P2 (60 s) or Ins(3,4)P2. When carbachol was displaced with atropine, after 1 h pre-stimulation, the maximal decreases in Ins(1,4,5)P3 and Ins1P from the stimulated steady state (5 s) clearly preceded those of the other metabolites. These declines were used to calculate the turnover times and rate of metabolic flux through the various inositol phosphates. These experiments confirmed the relatively minor importance of the Ins(1,3)P2 pathway (less than 10% of the total flux) and demonstrated that Ins(1,4,5)P3 removal was evenly distributed through the Ins(1,4)P2 and Ins(1,3,4,5)P4 routes. They also established that flux through Ins1P was 8-fold greater than that through Ins(1,4,5)P3, indicating that the former could not have been derived from PtdInsP2 hydrolysis. Similarly, in islets pretreated with neomycin, which binds to PtdInsP2 with greater affinity than to PtdIns, the increase in Ins1P caused by 1 min stimulation with carbachol was not affected, despite virtual abolition of the increase in Ins4P, and an overall inhibition of PtdInsP2 hydrolysis by 67%. The results indicate that, in addition to PtdInsP2 breakdown, carbachol also promotes a rapid PtdIns hydrolysis which becomes increasingly predominant with prolonged stimulation. PMID- 1637345 TI - Kinetic studies of the polygalacturonase enzyme from Colletotrichum lindemuthianum. AB - The intrinsic protein fluorescence of the polygalacturonase from Colletotrichium lindemuthianum was exploited in stopped-flow experiments aimed at elucidating the kinetic mechanism for this enzyme. Binding of the polymeric substrate polygalacturonic acid (PGA) essentially produced a triphasic fluorescence profile. There was an initial rapid quench in fluorescence, consistent with the rapid formation of the enzyme-substrate complex, with an equilibrium constant of about 8 x 10(-4)% (w/v) PGA (about 0.27 microM). There then followed a near constant fluorescence phase, attributable to turnover of the enzyme-substrate complex as a steady-state intermediate. As the concentration of the steady-state intermediate became depleted, towards the end of the reaction, there was a partial return of the fluorescence intensity. This phase is attributed to a final, single turnover of the enzyme at the end of the reaction. The fluorescence intensity does not return to its original level due to product remaining bound at the end of the reaction. PMID- 1637346 TI - Inhibition of steroid 5 alpha-reductase by specific aliphatic unsaturated fatty acids. AB - Human or rat microsomal 5 alpha-reductase activity, as measured by enzymic conversion of testosterone into 5 alpha-dihydrotestosterone or by binding of a competitive inhibitor, [3H]17 beta-NN-diethulcarbamoyl-4-methyl-4-aza-5 alpha androstan-3-one ([3H]4-MA) to the reductase, is inhibited by low concentrations (less than 10 microM) of certain polyunsaturated fatty acids. The relative inhibitory potencies of unsaturated fatty acids are, in decreasing order: gamma linolenic acid greater than cis-4,7,10,13,16,19-docosahexaenoic acid = cis 6,9,12,15-octatetraenoic acid = arachidonic acid = alpha-linolenic acid greater than linoleic acid greater than palmitoleic acid greater than oleic acid greater than myristoleic acid. Other unsaturated fatty acids such as undecylenic acid, erucic acid and nervonic acid, are inactive. The methyl esters and alcohol analogues of these compounds, glycerols, phospholipids, saturated fatty acids, retinoids and carotenes were inactive even at 0.2 mM. The results of the binding assay and the enzymic assay correlated well except for elaidic acid and linolelaidic acid, the trans isomers of oleic acid and linoleic acid respectively, which were much less active than their cis isomers in the binding assay but were as potent in the enzymic assay. gamma-Linolenic acid had no effect on the activities of two other rat liver microsomal enzymes: NADH:menadione reductase and glucuronosyl transferase. gamma-Linolenic acid, the most potent inhibitor tested, decreased the Vmax. and increased Km values of substrates, NADPH and testosterone, and promoted dissociation of [3H]4-MA from the microsomal reductase. gamma-Linolenic acid, but not the corresponding saturated fatty acid (stearic acid), inhibited the 5 alpha-reductase activity, but not the 17 beta dehydrogenase activity, of human prostate cancer cells in culture. These results suggest that unsaturated fatty acids may play an important role in regulating androgen action in target cells. PMID- 1637347 TI - An e.x.a.f.s. study of the manganese O2-evolving complex in purified Photosystem II membrane fractions. The S1 and S2 states. AB - Manganese K-edge X-ray spectra have been obtained for Photosystem II samples isolated using Triton X-100 detergent and samples further purified by n-heptyl beta-D-thioglucoside detergent treatment to remove light-harvesting polypeptides and low-affinity calcium. The structure of the manganese complex is very similar for the two detergent preparations used. Analysis of the e.x.a.f.s. spectra for samples in the S1 and S2 states indicate changes in bond lengths for the shells of oxygen/nitrogen atoms. For the S1 state, oxygen shells at 0.181 and 0.193 nm (1.81 and 1.93 A) were observed and one manganese shell at 0.270 nm (2.70A). In the S2 state the oxygen bond lengths are longer at 0.184 and 0.200 nm (1.84 and 2.00 A). Additionally a shell of scatterers at 0.37 nm (3.7 A) was observed in both states which could be fitted to models with calcium scatterers at this distance. PMID- 1637348 TI - Effects of detergent on the sulphation of chondroitin by cell-free preparations from chick-embryo epiphyseal cartilage. AB - The effects of the non-ionic detergent Triton X-100 on 6-sulphation of two species of endogenous nascent proteochondroitin by a chick-embryo cartilage microsomal system was examined. Sulphation of the larger (Type I) species with adenosine 3'-phosphate 5'-phosphosulphate was slightly diminished when Triton X 100 was present, whereas sulphation of the smaller (Type II) species was slightly enhanced. An ordered rather than random pattern of sulphation was obtained for the smaller proteoglycan, but with a considerably lower degree of sulphation than that of the larger proteochondroitin. These differences were consistent with other differences between these two species as described previously. Sulphation of exogenous [14C]chondroitin and exogenous proteo[3H]chondroitin by the microsomal system with Triton X-100 present produced ordered rather than random sulphation patterns. When a 100,000 g supernatant fraction was utilized for sulphation of [14C]chondroitin or proteo[3H]chondroitin, Triton X-100 was not needed, and ordered sulphation was still obtained. When hexasaccharide was used, sulphation of multiple N-acetylgalactosamine residues of the individual hexasaccharides resulted. This was relatively independent of Triton X-100 or the concentration of the hexasaccharide acceptors. With soluble enzyme, sulphation of multiple N-acetylgalactosamine residues on the individual hexasaccharide molecules was even greater, so that tri-sulphated products were found. This suggests that ordered rather than random sulphation of chondroitin with these enzyme preparations is due to enzyme-substrate interaction rather than to membrane organization. PMID- 1637350 TI - Regulation of carboxypeptidase E. Effect of pH, temperature and Co2+ on kinetic parameters of substrate hydrolysis. AB - Carboxypeptidase E is a member of the carboxypeptidase A and B gene family, with many of the putative active-site and substrate-binding residues conserved between these enzymes. However, the pH optimum of carboxypeptidase E is substantially lower than that of carboxypeptidases A and B. To evaluate whether the difference in the pH optima of these carboxypeptidases reflects fundamental differences in the ionization behaviour of active-site residues, the influence of pH on carboxypeptidase E activity was examined. The V(max) for hydrolysis of dansyl-Phe Ala-Arg is pH-independent between 5 and 7, but decreases at pH values below 5. The pKa for the group the protonation of which leads to the loss of activity is approximately 4.8, and the slope of the V(max.)/pH profile suggests that only a single ionizable group is involved. In contrast, Km and V(max.)/Km are dramatically influenced by pH over the range 5-7, with multiple ionizable groups detected in this pH range. The pKa of the group the protonation of which decreases the V(max.) of substrate hydrolysis is lower (4.5) for carboxypeptidase E which had been reconstituted with Co2+. The enthalpy of ionization of the group observed in the V(max.) profile for carboxypeptidase E is approx. 28.9 kJ/mol. These results are compatible with the active-site model of the homologous carboxypeptidase A: in this model the ionization of a metal-bound water molecule is responsible for the observed decrease in V(max.). PMID- 1637349 TI - Ecto-phosphorylation on aortic endothelial cells. Exquisite sensitivity to staurosporine. AB - One- and two-dimensional gel electrophoresis of proteins from bovine aortic endothelial cells (BAEC) incubated with [gamma-32P]ATP revealed the preferential labelling of a cell-associated 21 kDa substrate. The labelling of this band was detectable within 30 s, increased up to 30 min and was stable for at least 3 h following the wash-out of the ATP. This protein was also labelled after incubation of the cells with [gamma-35S]ATP. Incorporation of radioactivity into the 21 kDa band did not occur if the endothelial cells were treated with low concentrations of trypsin (0.01%) before or after the labelling period. The pattern of BAEC protein phosphorylation by [gamma-32P]ATP was completely different from that of the fetal calf serum used for the cell culture. The presence of serum during the incubation of BAEC with [gamma-32P]ATP did not modify qualitatively the labelling pattern and, in particular, did not enhance the phosphorylation of the 21 kDa substrate; this suggests that neither the kinase nor the 21 kDa substrate are adsorbed serum proteins. Staurosporine, a protein kinase inhibitor with low specificity, decreased the labelling of the 21 kDa protein with an IC50 of 2 nM. In contrast, at 100 nM, staurosporine did not decrease the accumulation of inositol phosphates induced by ATP via the activation of P2y receptors. These data indicate the presence of aortic endothelial cells of an ecto-kinase which uses extracellular ATP to produce the selective and long-lived phosphorylation of a 21 kDa endothelial substrate. Ecto phosphorylation of this protein might play a role in the modulation of endothelial cell functions by ATP, in addition to the P2y receptors [Boeynaems & Pearson (1990) Trends Pharmacol. Sci. 11, 34-37]. The exquisite sensitivity of ecto-phosphorylation to inhibition by staurosporine and its specific inhibition by some isoquinolinesulphonamide compounds provide potential pharmacological tools to investigate this hypothesis. PMID- 1637351 TI - Ceramide glycanase from the earthworm, Lumbricus terrestris. AB - Ceramide glycanase (CGase) is an enzyme that cleaves the linkage between the sugar chain and the ceramide. To make this enzyme readily available, we have developed a simple method for preparing it from the earthworm, Lumbricus terrestris. The method involves Bio-Gel A-0.5m, octyl-Sepharose and p aminophenylthiogalactoside-agarose column chromatography. By gel filtration, the molecular mass of earthworm CGase was found to be 43.7 kDa. With ganglioside GM1 as substrate, the optimal pH of this enzyme was found to be between pH 3.5 and 4.0. Earthworm CGase hydrolyses glycolipids only in the presence of a detergent. Among various bile salts tested, sodium cholate was found to be the most effective in stimulating the hydrolysis of GM1 by this enzyme. Earthworm CGase released intact glycan chains from various glycosphingolipids in which the glycan chain is linked to the ceramide through a beta-glucosyl linkage. It also detached glycan chains from lactosyldialkylglycerol and alkyl-beta-lactosides. PMID- 1637352 TI - Increasing the thermostability of the neutral proteinase of Bacillus stearothermophilus by improvement of internal hydrogen-bonding. AB - In an attempt to increase the thermostability of the neutral proteinase of Bacillus stearothermophilus the buried Ala-170 was replaced by serine. Molecular dynamics simulations showed that Ser-170 stabilizes the enzyme by formation of an internal hydrogen bond. In addition, the hydroxy group of Ser-170 could contribute to stability by filling an internal cavity. After the introduction of the mutation, using site-directed-mutagenesis techniques, an increase in stability of 0.7 +/- 0.1 degrees C was obtained. PMID- 1637353 TI - Involvement of GTP in cell-free activation of neutrophil NADPH oxidase. Studies with GTP analogues. AB - Activation of superoxide-producing NADPH oxidase of neutrophils requires the presence of cell membranes, cytosolic components and arachidonate and is markedly enhanced by non-hydrolysable analogues of guanine nucleotides, i.e. guanosine 5' [gamma-thio]triphosphate and guanosine 5'[beta gamma-imido]triphosphate (p[NH]ppG). Gel filtration and ultrafiltration of the cytosol decreased the basal activity of NADPH oxidase. Activity could be restored by GTP, suggesting participation of the nucleotide in basal activation. Preincubation of neutrophil cytosol with periodate-oxidized p[NH]ppG (ox-p[NH]ppG) followed by gel filtration resulted in a time-dependent enhancement of basal oxidase activity. The presence of GDP or GTP, but not ATP, during the incubation with ox-p[NH]ppG abolished this enhancement. These data are consistent with a stable association of ox-p[NH]ppG with an oxidase-linked cytosolic protein. SDS/PAGE of neutrophil cytosol preincubated with [3H]ox-p[NH]ppG revealed radioactivity in bands migrating as 100, 70, 47, 34 and 22 kDa proteins. Evidence for covalent labelling of the cytosolic protein p47-phox with [3H]ox-p[NH]ppG is presented. Heterogeneity of cytosolic GTP-binding sites and possible participation of protein p47-phox in functional interaction with GTP analogues during cell-free activation are suggested. PMID- 1637354 TI - A study of the chylomicron metabolism in WHHL rabbits after fat loading. Discrepancy between results based on measurement of apoprotein B-48 or retinyl palmitate. AB - We studied the metabolism of chylomicrons in homozygous Watanabe heritable hyperlipidaemic (WHHL) rabbits and in cholesterol-fed or normally fed New Zealand White (NZW) rabbits by measuring the concentrations of apoprotein B-48 and of retinyl palmitate in their serum after feeding fat plus this vitamin according to two different protocols. Compared with NZW controls, retinyl palmitate accumulated in both hyperlipidaemic groups under study, not only in the d less than 1.019 fraction but also in the low-density lipoprotein (LDL) fraction. A strong correlation was found between the retinyl palmitate concentration in either the d less than 1.019 fraction or the LDL fraction of the WHHL rabbits and the concentrations of cholesterol and triacylglycerols in these fractions. This suggests that retinyl palmitate is exchanged rapidly between exogenous and endogenous lipoproteins. This is supported by the lack of a correlation between the retinyl palmitate concentrations and the intensity of the apoprotein B-48 band in the respective d less than 1.019 fractions or LDL fractions; in most fractions, in which large amounts of retinyl palmitate were present, the intensity of the apoprotein B-48 band was not increased compared with the fasting concentrations. Assuming that retinyl palmitate is a marker for the transfer of exogenous lipids, the results of our experiments indicate that the removal of exogenous lipids is delayed by complexing to endogenously synthesized lipoproteins. However, the clearance of apoprotein B-48 is normal and thus independent of the LDL-receptor activity. PMID- 1637355 TI - Metabolism of R- and S-1,3-butanediol in perfused livers from meal-fed and starved rats. AB - The metabolism of millimolar concentrations of R- or S-1,3-butanediol has been studied in perfused livers from fed and starved rats. Protocols were designed to measure in the same experiment (i) uptake of the diol, (ii) the contribution of the diol to ketogenesis, (iii) the contribution of the diol to total fatty acid plus sterol synthesis, and (iv) conversion of S-1,3-butanediol into S-3 hydroxybutyrate. Our data show that R- and S-1,3-butanediol are taken up by the liver at the same rate. Most of the metabolism of R-1,3-butanediol is accounted for by conversion to the physiological ketone bodies R-3-hydroxybutyrate and acetoacetate. Only 29-38% of S-1,3-butanediol uptake is accounted for by conversion into physiological ketone bodies. The balance of S-1,3-butanediol metabolism is conversion to S-3-hydroxybutyrate, lipids and CO2. PMID- 1637356 TI - Triacylglycerol accumulation and secretion in hepatocyte cultures. Effects of insulin, albumin and Triton WR 1339. AB - We have investigated the possibility that the apparent inhibition of very-low density lipoprotein (VLDL)-triacylglycerol secretion by the addition of insulin to rat hepatocyte cultures may result from insulin-mediated enhancement of hepatic lipase secretion and, consequently, of extracellular triacylglycerol hydrolysis. We have, therefore, studied the effects of the inhibitor of lipase activity, Triton WR 1339, on the secretion of triacylglycerol by cultured rat hepatocytes. Incubation of hepatocyte cultures with increasing concentrations of Triton WR 1339 increased the accumulation of acylglycerol in the medium, suggesting that, in normal incubations, a substantial rate of degradation of secreted triacylglycerol does occur and that it results in an under-estimation of the rate of triacylglycerol secretion. However, Triton did not counteract the inhibitory effects of insulin, suggesting that the observed increased activity of hepatic lipase induced by the hormone cannot account for the inhibition of acylglycerol accumulation in the medium that occurred in the presence of insulin. BSA increased the accumulation of triacylglycerol in culture media by about 2 fold and also decreased the activity of hepatic lipase by 80%. A causative relationship between these two effects was supported by the further observation that Triton abolished the effects of BSA on triacylglycerol accumulation in the medium. The implications of these data for the validity of the use of Triton for the study of hepatic rates of triacylglycerol production in vivo and of secretion by hepatocytes in vitro are discussed. PMID- 1637357 TI - Expression of Pseudomonas aeruginosa nitrite reductase in Pseudomonas putida and characterization of the recombinant protein. AB - Nitrite reductase from Pseudomonas aeruginosa has been successfully expressed in Pseudomonas putida. The purified recombinant enzyme contains haem c but no haem d1. Nonetheless, like the holoenzyme from Ps. aeruginosa, it is a stable dimer (molecular mass 120 kDa), and electron transfer to oxidized azurin is biphasic and follows bimolecular kinetics (k1 = 1.5 x 10(5) and k2 = 2.2 x 10(4) M-1.s-1). Unlike the chemically produced apoenzyme, recombinant nitrite reductase containing only haem c is water-soluble, stable at neutral pH and can be quantitatively reconstituted with haem d1, yielding a holoenzyme with the same properties as that expressed by Ps. aeruginosa (namely optical and c.d. spectra, molecular mass, cytochrome c551 oxidase activity and CO-binding kinetics). PMID- 1637358 TI - Selective oxidation of histidine residues in proteins or peptides through the copper(II)-catalysed autoxidation of glucosone. AB - Glucosone has been identified as the main intermediate sugar moiety product of the copper(II)-catalysed autoxidation of the Amadori compound [Kawakishi, Tsunehiro & Uchida (1991) Carbohydr. Res. 211, 167-171]. Oxidative fragmentation of the model protein, especially selective degradation of the histidine residue in protein or peptides mediated by the copper(II)-catalysed autoxidation of glucosone, is discussed in this paper. The oxidative damage to protein could be retarded by catalase (EC 1.11.1.16) and EDTA, while superoxide dismutase (EC 1.15.1.1) and hydroxyradical scavengers showed little effect. Through the process of the oxidative degradation of N-benzoylhistidine and other histidine-containing peptides, the oxidation of the imidazole ring in histidine caused by the glucosone-copper(II) system was the same as that by the ascorbate-copper(II) system. These facts suggest that the copper-catalysed autoxidation of glucosone could generate some active-oxygen species causing oxidative damage to protein similar to that caused by the ascorbate-copper(II) system. PMID- 1637359 TI - Dual role for protein kinase C alpha as a regulator of ion secretion in the HT29cl.19A human colonic cell line. AB - The involvement of protein kinase C (PKC) in the regulation of intestinal ion secretion was studied in polarized monolayers of the HT29cl.19A human colon carcinoma cell line. Carbachol, phorbol esters [PMA (phorbol 12-myristate 13 acetate) and PDB (phorbol 12,13-dibutyrate)] and 8-bromo cyclic AMP (8-Br-cAMP) induced Cl secretion, as measured by a rise in the short-circuit current (ISC). The electrical response to carbachol coincided with a transient translocation of PKC alpha from the soluble to the particulate fraction. The carbachol-, PDB- and 8-Br-cAMP-induced ISC responses were inhibited by pretreatment of the cells with PMA (0.5 microM) for 2 h, a time period in which PKC alpha, beta 1 and gamma levels were not changed. As shown by 86Rb+ and 125I- efflux studies, the main targets for this inhibition were basolateral K+ transporters rather than apical Cl- channels. Prolonged exposure to PMA (24 h) led to a 60% recovery of the 8-Br cAMP response, but not of the carbachol- or PDB-provoked secretion. As shown by immunoblotting with PKC-isoenzyme-specific antisera, the recovery of the 8-Br cAMP response coincided with the down-regulation of PKC alpha, whereas the levels of PKC beta 1 and gamma were unmodified. These results suggest that PKC alpha, but not PKC beta 1 or gamma, is involved in both acute stimulation and chronic inhibition of ion secretion in the HT29cl.19A colonic cell line. PMID- 1637360 TI - DNA precursor asymmetries, replication fidelity, and variable genome evolution. AB - Balanced pools of deoxyribonucleoside triphosphates (dNTPs) are essential for DNA replication to occur with maximum fidelity. Conditions that create biased dNTP pools stimulate mutagenesis, as well as other phenomena, such as recombination or cell death. In this essay we consider the effective dNTP concentrations at replication sites under normal conditions, and we ask how maintenance of these levels contributes toward the natural fidelity of DNA replication. We focus upon two questions. (1) In prokaryotic systems, evidence suggests that replication is driven by small, localized, rapidly replenished dNTP pools that do not equilibrate with the bulk dNTP pools in the cell. Since these pools cannot be analyzed directly, what indirect approaches can illuminate the nature of these replication-active pools? (2) In eukaryotic cells, the normal dNTP pools are highly asymmetric, with dGTP being the least abundant nucleotide. Moreover, the composition of the dNTP pools changes as cells progress through the cell cycle. To what extent might these natural asymmetries contribute toward a recently described phenomenon, the differential rate of evolution of different genes in the same genome? PMID- 1637361 TI - Biological asymmetries and the fidelity of eukaryotic DNA replication. AB - A diploid human genome contains approximately six billion nucleotides. This enormous amount of genetic information can be replicated with great accuracy in only a few hours. However, because DNA strands are oriented antiparallel while DNA polymerization only occurs in the 5'----3' direction, semi-conservative replication of double-stranded DNA is an asymmetric process, i.e., there is a leading and a lagging strand. This provides a considerable opportunity for non random error rates, because the architecture of the two strands as well as the DNA polymerases that replicate them may be different. In addition, the proteins that start or finish chains may well be different from those that perform the bulk of chain elongation. Furthermore, while replication fidelity depends on the absolute and relative concentrations of the four deoxyribonucleotide precursors, these are not equal in vivo, not constant throughout the cell cycle, and not necessarily equivalent in all cell types. Finally, the fidelity of DNA synthesis is sequence-dependent and the eukaryotic nuclear genome is a heterogeneous substrate. It contains repetitive and non-repetitive sequences and can actually be considered as two subgenomes that differ in nucleotide composition and gene content and that replicate at different times. The effects that each of these asymmetries may have on error rates during replication of the eukaryotic genome are discussed. PMID- 1637362 TI - From cell fates to morphology: developmental genetics of the Caenorhabditis elegans male tail. AB - The C. elegans male tail is being studied as a model to understand how genes specify the form of multicellular animals. Morphogenesis of the specialized male copulatory organ takes place in the last larval stages during male development. Genetic analysis is facilitated because the structure is not necessary for male viability or for strain propagation. Analysis of developmental mutants, isolated in several functional and morphological screens, has begun to reveal how fates of cells are determined in the cell lineages, and how the specification of cell fates affects the morphology of the structure. Cytological studies in wild type and in mutants have been used to study the mechanism of pattern formation in the tail peripheral nervous system. The ultimate goal is to define the entire pathway leading to the male copulatory organ. PMID- 1637363 TI - Cutting, splicing, reordering, and elimination of DNA sequences in hypotrichous ciliates. AB - Hypotrichous ciliates extensively process genomic DNA during their life cycle. Processing occurs after cell mating, beginning with multiple rounds of DNA replication to form polytene chromosomes. Thousands of transposonlike elements are then excised from the chromosomes and destroyed, and thousands of short, internal eliminated sequences (IESs) are excised from coding and noncoding parts of genes and destroyed. IES removal from a gene is accompanied by splicing of the remaining chromosomal DNA segments to form a transcriptionally competent gene. For some genes these DNA segments are in a scrambled order and are ligated into a genetically correct order at the time of IES removal. Next the polytene chromosomes are cut up band-by-band and all genes are excised from the chromosomes as short, linear molecules averaging 2.2 kbp (in Oxytricha nova). Gene excision is accompanied by destruction of all nongenic DNA, which, together with the transposonlike elements and IESs, accounts for approximately 95% of the total sequence complexity of the genome in O. nova. Telomeric sequences are added to the excised gene-sized DNA molecules. Finally, the gene-sized molecules are replicated several times to form the macronucleus of the organism. PMID- 1637364 TI - Cancer predisposition in Bloom's syndrome. AB - This article focuses upon defining those factors which may contribute to the pathogenesis of cancer. The molecular basis of tumour etiology is discussed with reference to cancer predisposing syndromes, and in particular to the human inherited disease, Bloom's syndrome. In Bloom's syndrome, patients are predisposed to a wide variety of malignant disease. We propose a model in which overexpression of the ubiquitous c-myc proto-oncogene contributes to this process. PMID- 1637365 TI - RNA-binding proteins: masking proteins revealed. PMID- 1637366 TI - Induction mechanism of a single gene molecule: stochastic or deterministic? AB - A new field of gene expression regulation research is emerging that has previously been overlooked. This new area is concerned with distinguishing the expression of a single gene from the averaged expression of many gene copies within the cell population. This paper reviews research focused on individual genes in inducible gene expression systems. The main experimental strategy is to measure the gene expression level of a single cell containing a single reporter gene molecule. In contrast to the commonly held belief, gene induction is found to be stochastic under certain conditions. The possible mechanisms and implications are discussed. PMID- 1637367 TI - Prognostic significance of extent of nodal involvement in stage D1 prostate cancer treated with radiotherapy. AB - The records of 107 patients with newly diagnosed adenocarcinoma of the prostate irradiated with curative intent at Duke University Medical Center from 1970 through 1983 were reviewed. Forty patients (37%) underwent standard bilateral pelvic lymph node dissection (PLND) prior to beginning irradiation. Twenty-four patients (22%) were found to have pelvic nodal metastases (Stage D1). Those found to have a single microscopically positive node at PLND may be curable with irradiation. In contrast, those with more extensive nodal metastases appear to be incurable with radiotherapy. Additional studies are needed to confirm or refute these findings. PMID- 1637368 TI - Psychoactive drug use in an institution for intellectually handicapped persons. PMID- 1637369 TI - The opioid system and the placebo response. PMID- 1637370 TI - Age associated memory impairment. PMID- 1637371 TI - Mortality in meningococcal disease. PMID- 1637372 TI - Income distribution and life expectancy. PMID- 1637373 TI - Variant-specific monoclonal and group-specific polyclonal human immunodeficiency virus type 1 neutralizing antibodies raised with synthetic peptides from the gp120 third variable domain. AB - The third variable (V3) domain of the human immunodeficiency virus type 1 (HIV-1) external membrane glycoprotein gp120 is of crucial importance in eliciting neutralizing antibodies in infected persons. Polyclonal (PAb) and monoclonal (MAb) antibodies directed against selected epitopes in the V3 domain are valuable tools for analysis of the involvement of such sequences in neutralization and for definition of the relation between amino acid variability and immunological cross reactions. The aim of this study was to obtain such site-specific antibodies. By using synthetic peptides derived from the V3 domain, a group-specific neutralizing PAb, two high-affinity HIV-1 IIIB neutralizing MAb, and two nonneutralizing MAb were raised. A 15-amino-acid peptide overlapping the tip of the V3 domain of HIV-1 MN was used to produce a rabbit PAb (W0/07). This PAb inhibited syncytium formation induced by HIV-1 IIIB and four field isolates. A similar IIIB-derived peptide was used to generate two murine immunoglobulin G1 (IgG1) MAb (IIIB-V3-13 and IIIB-V3-34). Pepscan analysis mapped the binding site of IIIB-V3-34 to the sequence IRIQRGPGR. The Kds of IIIB-V3-13 and IIIB-V3-34 for gp120 were 6.8 x 10(-11) and 1.6 x 10(-10) M, respectively. These MAb neutralized IIIB but not MN and inhibited syncytium formation induced by IIIB. They are applicable in enzyme-linked immunosorbent assays, immunocytochemistry, and flow cytometry. A peptide covering the left base of the V3 domain was used to generate two murine IgG1 MAb (IIIB-V3-21 and IIIB-V3-26). The binding site of IIIB-V3-21 was mapped to the sequence INCTRPN. These MAb did not neutralize HIV-1 and did not inhibit syncytium formation. This study supports the notion that HIV-1 neutralizing antibodies suitable for multiassay performance can be obtained with synthetic peptides and that high-affinity MAb can be generated. Such site specific antibodies are useful reagents in the analysis of HIV-1 neutralization. In addition, the cross-neutralization of different viral strains by PAb generated through single-peptide immunization is directly relevant to vaccine development. PMID- 1637374 TI - The signal for Golgi retention of bovine beta 1,4-galactosyltransferase is in the transmembrane domain. AB - The expression and localization of bovine beta 1,4-galactosyltransferase (Gal T) has been studied in mammalian cells transfected with Gal T cDNA constructs, and the role of the amino-terminal domains of Gal T in Golgi localization examined. Here we demonstrate that the transmembrane (signal/anchor) domain of bovine Gal T contains a positive Golgi retention signal. Bovine Gal T was characterized in transfected cells with anti-bovine Gal T antibodies, affinity-purified from a rabbit antiserum using a bacterial recombinant fusion protein. These affinity purified antibodies recognized native bovine Gal T and showed minimum cross reactivity with Gal T from non-bovine sources. Bovine Gal T cDNA was expressed, as active enzyme, transiently in COS-1 cells and stably in murine L cells, and the product was shown to be localized to the Golgi complex by immunofluorescence using the polypeptide-specific antibodies. A low level of surface bovine Gal T was also detected in the transfected L cells by flow cytometry. The removal of 18 of the 24 amino acids from the cytoplasmic domain of bovine Gal T did not alter the Golgi localization of the product transiently expressed in COS-1 cells or stably expressed in L cells. Both the full-length bovine Gal T and the cytoplasmic domain deletion mutant were N-glycosylated in the transfected L cells, indicating both proteins have the correct N(in)/C(out) membrane orientation. Deletion of both the cytoplasmic and signal/anchor domains of bovine Gal T and incorporation of a cleavable signal sequence resulted in a truncated soluble bovine Gal T that was rapidly secreted (within 1 h) from transfected COS 1 cells. Replacement of the signal/anchor domain of bovine Gal T with the signal/anchor domain of the human transferrin receptor resulted in the transport of the hybrid molecule to the cell surface of transfected COS-1 cells. Furthermore, a hybrid construct containing the signal/anchor domain of Gal T with ovalbumin was efficiently retained in the Golgi complex, whereas ovalbumin anchored to the membrane by the transferrin receptor signal/anchor was expressed at the cell surface of transfected COS-1 cells. Overall, these studies show that the hydrophobic, signal/anchor domain of Gal T is both necessary and sufficient for Golgi localization. PMID- 1637375 TI - Involuntary interventions: does the benefit exceed the cost? PMID- 1637376 TI - The duty to attend upon the sick. PMID- 1637377 TI - "It takes more than knowledge: it takes assertiveness". PMID- 1637378 TI - Biopesticides and resistance. PMID- 1637379 TI - Underreporting of pedestrian road accidents. PMID- 1637380 TI - Side of origin of epithelial ovarian cancer. PMID- 1637381 TI - Effect of anoxia on intracellular ATP, Na+i, Ca2+i, Mg2+i, and cytotoxicity in rat hepatocytes. AB - The effects of anoxia were studied in freshly isolated rat hepatocytes maintained in agarose gel threads and perfused with Krebs-Henseleit bicarbonate buffer (KHB). Cytosolic free calcium (Ca2+i) was measured with aequorin, intracellular sodium (Na+i) with SBFI, intracellular pH (pHi) with BCECF, lactic dehydrogenase (LDH) by the increase in NADH absorbance during lactate oxidation to pyruvate, ATP by 31P NMR spectroscopy in real time, and intracellular free Mg2+ (Mg2+i) from the chemical shift of beta-ATP relative to alpha-ATP in the NMR spectra. Anoxia was induced by perfusing the cells with KHB saturated with 95% N2, 5% CO2. After 1 h of anoxia, beta-ATP fell 66%, and 85% after 2 h, while the Pi/ATP ratio increased 10-fold from 2.75 to 28.3. Under control conditions, the resting cytosolic free calcium was 127 +/- 6 nM. Anoxia increased Ca2+i in two distinct phases: a first rise occurred within 15 min and reached a mean value of 389 +/- 35 nM (p less than 0.001). A second peak reached a maximum value of 1.45 +/- 0.12 microM (p less than 0.001) after 1 h. During the first hour of anoxia, Na+i increased from 15.9 +/- 2.4 mM to 32.2 +/- 1.2 mM (p less than 0.001), Mg2+i doubled from 0.51 +/- 0.05 to 1.12 +/- 0.01 mM (p less than 0.001), and pHi decreased from 7.41 +/- 0.03 to 7.06 +/- 0.1 (p less than 0.001). LDH release doubled during the first hour and increased 6-fold during the second hour of anoxia. Upon reoxygenation, ATP, Ca2+i, Mg2+i, Na+i, and LDH returned near the control levels within 45 min. To determine whether the increased LDH release was related to the rise in Ca2+i, and whether the increased Ca2+i was caused by Ca2+ influx, the cells were perfused with Ca(2+)-free KHB (+ 0.1 mM EGTA) during the anoxic period. After 2 h of anoxia in Ca(2+)-free medium, beta-ATP again fell 90%, but Ca2+i, after the first initial peak, fell below control levels, and LDH release increased only 2.7-fold. During reoxygenation, Ca2+i, ATP, Na+i, and LDH returned near the control levels within 45 min. These results suggest that the rise in Ca2+i induced by anoxia is caused by an influx of Ca2+ from the extracellular fluid, and that LDH release and cell injury may be related to the resulting rise in Ca2+i. PMID- 1637382 TI - Acrofacial dysostosis syndromes. PMID- 1637383 TI - A question of outcomes. PMID- 1637384 TI - The surgical management of vaginal vault prolapse. PMID- 1637386 TI - CPR in hospitalized patients. PMID- 1637385 TI - Bleeding pseudocysts and pseudoaneurysms in chronic pancreatitis. PMID- 1637387 TI - Insurance helpline. PMID- 1637388 TI - Sorry, I don't see nursing home patients. PMID- 1637389 TI - Time-cycled inverse ratio ventilation. PMID- 1637390 TI - Health care quality assurance: tracer analyses in quality assessment of ambulatory care provided by two outpatient teaching clinics. PMID- 1637391 TI - NANP responds to critics. PMID- 1637392 TI - Laryngeal mask airway for emergency cases. PMID- 1637393 TI - In obstetrics: there is an alternative to water. PMID- 1637394 TI - Unnecessary CT scans in stroke patients. PMID- 1637395 TI - Psychiatric diagnosis in a group of astronaut applications. PMID- 1637396 TI - Newer treatments beyond reach of Third World. PMID- 1637397 TI - Does increased lipase activity in serum imply damage to the pancreas? PMID- 1637398 TI - Changes in stimulating and blocking TSH receptor antibodies in a patient undergoing three cycles of transition from hypo to hyper-thyroidism and back to hypothyroidism. AB - We report a patient who underwent, over a mere 3-year period, three successive cycles of oscillation from hypo to hyper-thyroidism and back to hypothyroidism. This unusual sequence of events originated in a rare passage of primary hypothyroidism to hyper-thyroidism. The hyperthyroidism seemed typical of the autoimmune subgroup of toxic multinodular goitre. Stimulating and blocking TSH receptor antibody activities were measured (by cAMP functional bioassays using cultured human thyrocytes) during the course of the fluctuating phases of hypo and hyper-thyroidism. Measurement of such antibody activities revealed the coexistence of both stimulatory and blocking types of antibody in several serum samples from the patient. Throughout the whole course of alterations in thyroid function, thyroid stimulating antibodies were present. This was not the case with thyrotrophin receptor antibodies exhibiting TSH antagonist activity which seemed to appear and disappear. Monitoring such activity indicated that the emergence of blocking antibody seems to herald the onset of hypothyroidism. PMID- 1637399 TI - Cardioplegia with fluorescein for visualization of coronary arteries. PMID- 1637400 TI - The cholesterol controversy. PMID- 1637401 TI - Thrombosis and pulmonary embolism. PMID- 1637402 TI - Organ donation from intensive care units. PMID- 1637403 TI - Prescribing at the hospital-general practice interface. PMID- 1637404 TI - More on high-dose busulfan and seizure prophylaxis. PMID- 1637405 TI - Aluminum and Alzheimer's disease. PMID- 1637406 TI - Dipyridamole thallium-201 scintigraphy as a preoperative screening test. PMID- 1637407 TI - Countering cardiac counterpulsation. PMID- 1637408 TI - Melanomas that defy clinical recognition. PMID- 1637409 TI - Rhabdoid tumor of the central nervous system. PMID- 1637410 TI - Bone marrow transplant retinopathy. PMID- 1637411 TI - Factors associated with chronic lung disease in preterm infants. PMID- 1637412 TI - In response to position paper by National Council Against Health Fraud. PMID- 1637413 TI - Smoking and ischemic heart disease. PMID- 1637414 TI - Re: "Prenatal exposure to parents' smoking and childhood cancer". PMID- 1637415 TI - Therapeutic pulmonary artery catheterization. PMID- 1637416 TI - Appropriate in vivo expression of a muscle-specific promoter by using avian retroviral vectors for gene transfer [corrected]. AB - The promoter regions of the chicken skeletal muscle alpha-actin (alpha sk-actin) and the cytoplasmic beta-actin genes were linked to the bacterial chloramphenicol acetyltransferase (CAT) gene. Replication-competent retroviral vectors were used to introduce these two actin/CAT cassettes into the chicken genome. Chickens infected with retroviruses containing the alpha sk-actin promoter expressed high levels of CAT activity in striated muscle (skeletal muscle and heart); much lower levels of CAT activity were produced in the other nonmuscle tissues. In contrast, chickens infected with retroviruses containing the beta-actin promoter linked to the CAT gene expressed low levels of CAT activity in many different tissue types and with no discernible tissue specificity. Data are presented to demonstrate that the high levels of CAT activity that were detected in the skeletal muscle of chickens infected with the retrovirus containing the alpha sk-actin promoter/CAT cassette were not due to preferential infectivity, integration, or replication of the retrovirus vector in the striated muscles of these animals. PMID- 1637417 TI - Drug targeting with monoclonal antibodies. A review. AB - Monoclonal antibodies have been widely used in attempts to target anti-neoplastic agents selectively to tumours. Problems associated with the use of monoclonal antibodies as the targeting moiety include lack of complete tumour selectivity, antigenic heterogeneity, tumour access and immunogenicity. Considerable effort in the targeting field is being expended in an attempt to reduce or overcome these problems. Attachment of monoclonal antibodies to low molecular weight cytotoxic drugs, protein toxins, radionuclides or enzymes capable of conversion of inactive prodrugs to cytotoxic drugs, has, despite these problems, resulted in conjugates which do have selective anti-tumour effects in animal models. The advantages and limitations of these different approaches are reviewed. It remains to be established in man if any of these approaches will result in significant therapeutic benefit in major solid tumours. PMID- 1637418 TI - Expression of the murine homologue of the cell cycle control protein p34cdc2 in T lymphocytes. AB - The mammalian homologue of the cdc2 gene of the fission yeast Schizosaccharomyces pombe encodes a p34cdc2 cyclin-dependent kinase that regulates the cell cycle of a wide variety of cell types. Resting murine T lymphocytes contained no detectable p34cdc2 protein, histone kinase activity, or specific mRNA for the cdc2 gene. Activation of the T cells by immobilized anti-CD3 resulted in the expression of specific mRNA late in the G1 phase of the cell cycle, and p34cdc2 protein was detectable at or near G1/S. At this point in the cell cycle, the protein was phosphorylated at tyrosine and displayed no H1 histone kinase activity. As the cells progressed through the cycle, the amount of specific mRNA and p34cdc2 increased, and H1 histone kinase activity was detectable when the cells were blocked at G2/M by nocodazole. The activation of T cells by phorbol dibutyrate induced the expression of IL-2R but failed to induce the synthesis of IL-2 or the expression of cdc2-specific mRNA. Under these conditions, the activated cells failed to enter the S phase of the cell cycle. Because the presence of IL-2 added exogenously during activation by phorbol dibutyrate resulted in the expression of cdc2-specific mRNA and progression through the cell cycle, either IL-2 or the interaction with IL-2R may be involved in the expression of cdc2 and regulation of the G1/S transition. PMID- 1637419 TI - [Relapse prevention in liver transplant patients treated for liver involvement due to hepatitis B virus]. AB - Controversy surrounds the indication of liver transplantation in patients with hepatitis B virus infection. The major problem is the very high risk of infection of the graft. Some investigators have suggested that the presence of HBsAg is a contraindication to liver transplantation. Between February 1975 and December 1990, 178 HBs positive patients were transplanted at Paul Brousse Hospital in Professor H. Bismuth's Department, 137 for post hepatitis cirrhosis and 41 for fulminant hepatitis. Since April 1984 we have decided long term immunoprophylactic therapy for all patients with HBs infection. But only from August 1987 our supply of purified anti HBs immunoglobulin has been adequate to treat all our patients according to the following protocol: 10.000 IU during the peroperative phase, 10.000 IU immediately after intervention, 10.000 IU every day for the first 6 days, 10.000 IU when the anti HBs levels were under 150 IU/l. One hundred thirty-nine patients were treated by this method. 110 cleared HBs antigen from their sera and their liver were biologically and histologically free of B virus infection. 29 patients showed reappearance of HBs antigen in their sera and nearly all of them developed objective, histologically confirmed, graft lesions. These lesions are those of classical infection: acute hepatitis, active chronic hepatitis and cirrhosis. So 79% of patients were successfully treated with a follow up of 45 months to 6 months. We also studied the prognostic factors under treatment. The study shows: in the case of fulminant hepatitis, 93% success versus 77% in post hepatitis cirrhosis; in the case of Delta superinfection, 94% success versus 66% with pure B infection; in the absence of HBVDNA in the patient's sera before transplantation, 92% success versus 20% in the presence of HBVDNA. For a better understanding of the overall results, the two following parameters have to be considered: some patients relapsed after stopping their treatment, some other patients, despite repositivation of HBs antigen in their sera showed a paradoxal good evolution. These considerations enable us to obtain HBVDNA positive patients: 10% success, HBVDNA negative patients: Fulminant hepatitis: 100% success B Delta post hepatitis cirrhosis: 100% success B post hepatitis cirrhosis: 92% success. PMID- 1637420 TI - [Transfusion security and morbidity in France]. PMID- 1637421 TI - [DNA polymorphism in a Brazilian population: relationship to allele frequencies in France]. AB - The allele frequency distribution of two highly polymorphic DNA sequences was determined in a population from the metropolitan area of Fortaleza (Northeast Brazil). DNAs from 234 individuals were digested with Pvull and successively hybridized to each probe: alpha-Globin 3'HVR and Mucin HVR. The resulting allele frequencies were compared to those observed in a French population. There is no statistically significant difference between these populations in the 3'HVR system. On the contrary, the distribution is statistically different in the Mucin HVR/Pvull system. PMID- 1637422 TI - [Removal of plasma lipids by selective filtration]. AB - We herein describe a new depth filter media which exhibits selective adsorption properties for lipids of plasma on Zeta Plus Del I (Cuno Europe). Lipids plug chromatographic columns and filter during plasma fractionnation and cause solution instability for the final product. Several parameters which could affect the lipid removal efficiency on Zeta Plus Del I have been investigated: prefiltration, contact time, ionic strength, pH, and temperature. The maximum percentage of total lipids eliminated, in the better operating conditions was 68%. This method has proven to be efficient for the treatment of plasmatic lipids and can be easily incorporated in an industrial process. PMID- 1637423 TI - Arthroscopic subacromial decompression: a clinical review. AB - Arthroscopic subacromial decompression has become a popular technique supplanting the open Neer acromioplasty in many instances of chronic rotator cuff disease. A review of 61 consecutive decompressions with a minimum follow-up of 12 months was undertaken to evaluate preoperative criteria and surgical outcomes. Of the 61 patients, 53 patients with an average follow-up of 23 months were available for review. Thirty-four men and 19 women with an average age of 47 years comprised the study group. Eleven (21%) had full-thickness tears, 35 (66%) had partial thickness injuries, and 7 (13%) had normal-appearing rotator cuffs at the time of arthroscopy. The UCLA shoulder rating system was used to evaluate outcome. Eighty one percent of the patients had an excellent (32%) or good (49%) result whereas 19% (15% fair and 4% poor) were considered unsatisfactory. Those with early impingement findings and partial rotator cuff tears were likely to experience a satisfactory outcome. Patients with full-thickness rotator cuff tears were less likely to experience a successful result (55%). Workmen's compensation cases had a satisfactory outcome in 74%, with a predominance of good over excellent results. Excluding those with full-thickness tears and work-related injuries, a satisfactory outcome was achieved in 90%. Arthroscopic subacromial decompression for mechanical impingement of the rotator cuff is a technically demanding procedure requiring appropriate skills as well as careful preoperative treatment and evaluation. For individuals in whom conservative measures fail and who meet stringent criteria, namely, a largely intact rotator cuff and a non-work-related injury, a highly reliable and satisfying outcome can be anticipated by both patient and surgeon. PMID- 1637424 TI - Use of an electrocautery loop probe for arthroscopic meniscectomy: a five-year experience with results, indications, and complications. AB - Between 1984 and 1990, 952 patients had arthroscopic meniscectomies with a specially designed electrocautery loop probe. In all but 250 patients, 1.5% glycine was used as the nonconductive irrigating solution. Ninety-five patients had repeat arthroscopic procedures at a minimum of 6 months after their original procedure. Biopsies of the meniscal remnants were obtained in 21 patients. In all 21, there was no evidence of thermal damage in the area of the previous arthroscopic meniscal electrosurgery. In less than 4% of the patients, articular surface injuries occurred at the time of the original meniscectomy. Careful records were kept outlining the areas of contact damage with the exposed wire of the electrocautery loop probe. At repeat arthroscopies in 17 patients 9 months to 4 years after the initial procedure, there was no apparent evidence of significant permanent damage to the articular surface in the area of the original thermal injury. The electrocautery loop probe was effective for efficient resection of simple and complex tears of the medial or lateral meniscus. PMID- 1637425 TI - Arthroscopic evaluation of allograft anterior cruciate ligament reconstruction. AB - In a previous study, we evaluated the findings of arthroscopic second looks at open anterior cruciate ligament reconstructions using autogenous tissue. We were disappointed at the variable quality of the ligaments and the presence of articular cartilage lesions. These findings led us to change our treatment protocol. Since 1983, we have used freeze-dried allografts for arthroscopic intraarticular ACL reconstructions. We have started protected motion in a brace immediately postoperatively and delayed weightbearing for 12-16 weeks. A total of 54 patients with at least a 2-year follow-up were evaluated subjectively (Lysholm scale) and objectively (KT 1000). Some 78% were rated good or excellent, and 87% were satisfied with their surgery. Of these 54 patients, 28 underwent subsequent surgery for hardware removal, manipulation, or removal of adhesions. All 28 had an arthroscopy, and an evaluation of ligamentous tissue and articular cartilage at the time of the second surgery. The graft resembled a normal anterior cruciate ligament in 18 patients. The graft was slightly lax in two of these patients, but their clinical examination revealed normal stability. In six patients, the intercondylar notch was covered by a sheath of dense, fibrous tissue, but the knees were stable. In two cases, there was slight fraying of the lateral aspect of the graft from impingement on the lateral femoral condyle. In two cases the graft failed. The condition of the articular cartilage was documented and compared with the condition of the articular cartilage at the time of cruciate reconstruction. In 19 cases, the articular cartilage had been normal and remained normal at the time of reevaluation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637426 TI - Augmentation of the accuracy of percutaneous electrode implantation by using a modified arthroscope to guide insertion. AB - Using a clear polyvinyl fluoride sheath over an arthroscope, inserted through a 1 cm stab incision, we have demonstrated the feasibility of visualizing the sciatic nerve and its branches in the feline model. The purpose of this technique is to allow visual control, without a large surgical incision, of the exact site of implantation of electrodes used for functional neuromuscular stimulation. Currently, we determine the optimum site for percutaneous electrode implantation by stimulating the target nerve or muscle with a 26-gauge probe needle until maximal response is obtained. This method lacks accuracy because there is no direct visualization of the location of the tip of the probe or the electrode. With the new technique, we identified nerves by their distinctive vascular markings and we followed the nerves with minimal disruption of the soft tissues. In this way, individual branches were identified and targeted for instrumentation, allowing selective stimulation of specific muscle groups. PMID- 1637427 TI - The intra-articular pressure of the shoulder: an experimental study on the role of the glenoid labrum in stabilizing the joint. AB - It was shown on human corpses that the glenohumeral joint may be compared to a piston surrounded by a valve. The glenoid labrum, then, should work like the valve block, sealing the joint from atmospheric pressure. In order to test this hypothesis, 18 human shoulder preparations were studied. The mean stabilizing force obtained by atmospheric pressure was 146 N. Additionally, 15 patients without any sign of instability and 17 patients with an anterior instability of the shoulder were tested under general anesthesia. In stable shoulder joints, traction at the arm caused negative intra-articular pressure that could be correlated to the amount of force exerted. In contrast, unstable shoulder joints with a tear of the glenoid labrum (Bankart lesion) did not exhibit this phenomenon. For unstable shoulder joints, the piston-and-valve model is no longer valid. This enlarges the current concept of shoulder joint stability in two ways: (a) the absence of negative intra-articular pressure disturbs joint mechanics and (b) altered pressure receptors might disturb motor coordination that dynamically protects the shoulder from dislocating forces. PMID- 1637428 TI - Subacromial impingement: open versus arthroscopic decompression. AB - An analysis of the follow-up results of 53 patients treated by an arthroscopic decompression (AD) and 53 patients treated by an open decompression (OD) is presented. Patients were evaluated pre- and postoperatively with the UCLA Shoulder Rating Scale, which includes an assessment of pain, function, range of motion, strength, and patient satisfaction. After an average of 20.1 months for the AD group and 27.3 months for the OD group, good or excellent results were found in 83.1% in the AD group and in 81.1% in the OD group. Patient satisfaction was 88.3% (AD) compared with 94.3% (OD). Results of decompression in both groups were not influenced by associated pathologies (acromioclavicular degeneration, frozen shoulder, calcified tendinitis, rotator cuff lesions). PMID- 1637429 TI - Comparison of initial pull-out strength of arthroscopic suture and staple Bankart repair techniques. AB - This study was performed to investigate the initial failure strength of arthroscopic suture and staple techniques use to treat recurrent anterior shoulder instability. Eight canine shoulder complexes were fashioned so that four 1-cm wide strips of capsule remained attached to the glenoid in each specimen (total of 32 test specimens) these specimens were tested to tensile failure on an Instron model 1331 testing machine either intact (n = 5), or after the capsule was sharply dissected off the bone and repaired with an arthroscopic staple (n = 11) or arthroscopic suture technique (n = 12). The control group failed at 17.75 +/- 7.14 kg, the suture repair at 11.0 +/- 2.56 kg, and the staple repair at 4.77 +/- 2.32 kg. These failure strengths were all statistically different from each other (p less than 0.0001). All failures occurred at the capsular bone interface. The authors do not advance one technique over the other but do advise surgeons to be mindful of the results when instituting early shoulder motion after arthroscopic Bankart procedures. PMID- 1637430 TI - Arthroscopic treatment of calcific tendinitis of the shoulder. AB - The results of arthroscopic treatment of chronic resistant calcific tendinitis of the shoulder in twenty-three patients were evaluated. Each patient had greater than 1 year of unsuccessful nonoperative management prior to arthroscopic surgery. The average age was 49 years (range 33-60) and average follow up was 26 months (range 12-47). Subacromial bursectomy was performed in all patients. Based on follow-up radiographs, thirteen patients had partial calcium removal while nine had complete removal of calcium. Results were graded as good in eleven patients (50%) with full motion and complete pain relief, satisfactory in nine (41%) patients with full motion and occasional episodes of pain, and unsatisfactory in two (9%) patients with persistent pain. Arthroscopic calcium removal and subacromial bursectomy are reasonable alternatives in the treatment of chronic calcific tendinitis resistant to conservative treatment. PMID- 1637431 TI - Extension-supination sign in prearthroscopic elbow distension. AB - A clinical sign of extension and supination of the elbow is described after prearthroscopic distension with fluid. When elicited, intra-articular fluid placement is indicated, assisting correct location of the arthroscope within the joint. PMID- 1637433 TI - Wrist arthroscopy: indications and results. AB - The results of 84 wrist arthroscopies in 74 patients (performed by the same surgeon) were reviewed retrospectively. Arthroscopies were categorized as "diagnostic"--to identify unknown pathology, "staging"--to assess the severity of known pathology, and "operative"--to treat known pathology. Ninety-eight percent of diagnostic arthroscopies accurately established details of the pathology in question. Ninety-six percent of staging arthroscopies helped guide future clinical management. Of the patients in the operative category, 35% improved after treatment with arthroscopy alone, requiring no further surgical intervention. This study shows that wrist arthroscopy is a powerful diagnostic and staging tool and suggests that it may also develop into a valuable treatment modality. PMID- 1637432 TI - Evaluation of the triangular fibrocartilage complex tears by arthroscopy, arthrography, and magnetic resonance imaging. AB - Arthroscopic findings in 11 patients with chronic ulnar painful wrist were compared both with arthrographic and magnetic resonance (MR) imaging results to evaluate the accuracy of the former procedure in the detection of triangular fibrocartilage complex (TFCC) lesions. MR imaging and arthrography investigations appeared to be sensitive modalities when compared with arthroscopic findings in TFCC lesions (specificity 100%; sensitivity 82 and 80%). MR imaging can be advantageously employed in the screening of patients suspected of having a TFCC tear, eliminating the necessity of an arthrographic examination. However, MR imaging could not define the exact site of the tear within the degenerate TFCC or detect lesions of the articular cartilage. Arthroscopy offers sure evidence of the site of TFCC lesion and more information about the intraarticular associated causes of chronic ulnar wrist pain such as chondromalacia and synovitis. An added benefit is that many of the pathologies seen can be treated using arthroscopic surgical techniques. PMID- 1637434 TI - Anatomic and biomechanical analysis of the arthroscopic wafer procedure. AB - The ulnar impaction syndrome is a common clinical entity that is most often associated with positive ulnar variance and is characterized by triangular fibrocartilage complex (TFCC), lunate, and/or distal ulnar pathology. Traditional treatment for symptomatic ulnar impaction syndrome has been conservative; however, in cases refractory to nonoperative management, formal ulnar shortening has been successful in long-term clinical series. Recently, arthroscopic ulnar shortening, the "arthroscopic wafer procedure" (AWP) (debridement of the perforated TFCC margins and limited ulnar head resection using a motorized burr) has become an option to treat this clinical syndrome. In an attempt to evaluate the biomechanical efficacy of the AWP, an experimental study was undertaken using nine ulnar positive cadaver forearms. Each specimen was evaluated biomechanically using axial load cells and pressure-sensitive film to evaluate the effect of serial resection of the TFCC and distal ulna on axial load and ulnar carpal pressures. The results of this experimental study revealed a statistically significant unloading of the ulnar aspect of the wrist after excision of the centrum of the TFCC and resection of the radial two-thirds width of the ulnar head, to a depth of subchondral bone resection. Furthermore, additional bony resection tended to correlate favorably with the stage of TFCC pathology noted, i.e., the more advanced the stage, the more resection necessary to unload the ulnar aspect of the wrist. Based on this biomechanical study, a limited clinical series has been initiated with early favorable results. The AWP biomechanically unloads the ulnar carpal complex, and therefore has a theoretical potential of relieving the symptoms of the ulnar impaction syndrome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637435 TI - Septic arthritis following arthroscopy: clinical syndromes and analysis of risk factors. AB - During a 4-year study of 4,256 knee arthroscopies, eighteen patients became infected (infection rate 0.42%). Occurrence of infection was strongly associated with use of long-acting intraarticular intraoperative corticosteroids. Infection was more common among patients with longer surgery operating times, increased numbers of procedures during surgery, prior procedures, and performance of chondroplasty or soft tissue debridement. Subsequent to the study, the infection rate fell to 0.1%. Twenty-four infections were studied (our eighteen plus six other concurrent community cases); twelve were due to Staphylococcus aureus, eleven to coagulase-negative staphylococci, and one to Enterobacter cloacae. Seventy percent of the patients had onset of symptoms within 3 days of surgery. Most patients with coagulase-negative staphylococcal infections had fevers less than 38.3 degrees C (101 degrees F), negative Gram stains on synovial fluid, normal peripheral leukocyte counts, and somewhat indolent, mild clinical syndromes, while most patients with S. aureus infections had higher fevers, positive synovial Gram stains, peripheral leukocytosis, and more acute and severe clinical syndromes. Knee pain, swelling, and warmth always occurred, but erythema was noted in only 30% of patients. Treatment with 2 weeks of intravenous antibiotics was successful in all but one patient. Long-term results were excellent in sixteen of twenty-two patients. PMID- 1637436 TI - Complications associated with the use of an infusion pump during knee arthroscopy. AB - This is a report of four complications from the use of an automated arthroscopy pump in 283 patients undergoing knee arthroscopy. The first patient had extravasation of fluid into the thigh, requiring discontinuation of the procedure. The second patient developed a compartment syndrome of the leg, necessitating a four-compartment fasciotomy of the leg. The third patient developed severe fluid extravasation into the anterior thigh compartment. A limited fasciotomy of the anterior thigh compartment was performed. The fourth patient developed moderate extravasation into the anterior part of the thigh and groin, necessitating discontinuation of pump irrigation and conversion to gravity irrigation to complete a partial medial meniscectomy. During a 15-month period, a complication rate of 1.4% from fluid extravasation during knee arthroscopy was noted. This review represents our initial experience with the infusion pump. No cases of fluid extravasation have occurred subsequently during a 12-month period. PMID- 1637437 TI - Anterior cruciate ligament tears in skeletally immature patients: meniscal pathology at presentation and after attempted conservative treatment. AB - We evaluated 12 skeletally immature patients with acute, intrasubstance tears of the anterior cruciate ligament (ACL) and open physes for meniscal pathology. Arthrograms were completed in 10 of 12 patients, and subsequent arthroscopy confirmed 8 meniscal tears (4 medial, 4 lateral) in 6 patients. Four patients with repairable menisci underwent arthroscopic meniscal repair and stabilization. Eight patients received quadriceps and hamstrings rehabilitation and returned to sports with a brace. After return to sports, all braced patients developed instability with multiple episodes of "giving way." Average time from initial injury to first episode of instability was 7 months. Seven patients sustained further meniscal damage an average of 15 months (range 7-27 months) after initial injury. We conclude that meniscal pathology is commonly associated with ACL tears in skeletally immature patients and we recommend arthrography or arthroscopy to evaluate patients with suspected ACL tears. Brace management did not prevent instability or new meniscal tears. PMID- 1637438 TI - A new femoral drill guide for arthroscopically assisted anterior cruciate ligament replacement. AB - There are an increasing number of drill guides and methods of selecting the most isometric femoral attachment site for reconstruction of the anterior cruciate ligament (ACL); some of these are complex and time-consuming. The senior author (R.P.) has developed a simple "inside-out" arthroscopic femoral drill guide, which is designed to reliably locate the optimal femoral attachment site. The accuracy and reliability of this guide was assessed in 10 cadaver knees. The isometry of semitendinosus tendon (ST), then patellar bone-tendon-bone (BTB) grafts was assessed in each knee. In no instance, for either reconstruction, was there greater than 3 mm graft movement through a full range of knee motion. Based on this study, we therefore conclude that this very simple drill guide is a useful tool in arthroscopic ACL reconstruction to quickly, easily, and reliably select the optimal femoral attachment site. It also negates the need for a lateral incision when using a BTB graft, thus reducing morbidity and improving cosmesis. PMID- 1637439 TI - Knee arthroscopy using local anesthesia. AB - This study confirms the feasibility of performing arthroscopy and arthroscopic surgery with patients under local anesthesia. Seventy patients underwent arthroscopy under local anesthesia using mepivacaine with adrenaline. In 49 patients, arthroscopic surgery was performed. It is important to wait at least 20 min after the injection of the anesthetic before surgery to anesthetize the medial part of the joint. There were few complications. Diagnostic and surgical arthroscopy can be successfully performed in the majority of patients with local anesthesia. PMID- 1637440 TI - Roentgenographic changes after arthroscopic meniscectomy: five-year follow-up in patients more than 45 years old. AB - Fifty knees with a mean follow-up time of greater than 5 years after arthroscopic meniscectomy were evaluated clinically and roentgenographically. Clinically, patients did well, with 98% patient satisfaction and 90% good or excellent results based on a modified Lysholm score. Although postoperative roentgenography showed some progression of Fairbank's changes in 61% with significant progression in 15% of knees, when changes in the nonoperative knee were considered, only 40% of operative knees showed progression, with only 4% of these knees showing significant progression. Normal results on preoperative anteroposterior roentgenography with the patient weight bearing and an anatomic tibiofemoral axis of greater than or equal to 4 degrees of valgus correlated with better long-term roentgenographic results. PMID- 1637441 TI - Arthroscopic meniscal repair: a posterior cannulated technique. AB - A modified inside-to-outside technique of meniscal repair is presented. The technique employs a 14 gauge needle that acts as the receiving conduit for a standard 10 in meniscal repair needle. The repair needle is placed into the joint through a repair cannula in a routine manner. Twenty-four meniscal repairs with an average follow-up of 26 months are presented with a clinical success rate of 92% and no complications. The technique provides a particularly effective and safe approach to the placement of meniscal repair sutures at the posterior extremes of medial and lateral meniscal tears. PMID- 1637442 TI - The diagnostic potential of synovial effusion in meniscal pathology. AB - During a 20-month period, 382 arthroscopies were performed and the type of washout fluid obtained was noted. When a torn meniscus was found, the fluid was macroscopically abnormal in 97.4% of cases. A crystal clear washout was associated with no demonstrable pathology in over half the cases, the remainder having mainly patellofemoral joint pathology and other articular lesions. Only 6.3% of those with a clear fluid washout had meniscal pathology. Of those with abnormal fluid, 68% had meniscal pathology, with a normal arthroscopic examination being found in only 8.5%. In addition, when the fluid from traumatic effusions was examined microscopically, a typical droplet containing lipid crystals was found to be present and to account for an oily macroscopic appearance. These data support the use of fluid irrigation of the knee as a screening test for intraarticular pathology, especially of the menisci, that may allow a reduction in the number of negative arthroscopies. PMID- 1637443 TI - Localized chondrocalcinosis of the lateral tibial condyle presenting as a loose body in a young athlete. AB - Chondrocalcinosis, although very rare in young adults, can occur in some young patients. Although its presenting clinical history or radiographic findings may resemble those of an intraarticular loose body, chondrocalcinosis can occur in young athletes, possibly after repetitive microtrauma, and should be included in the differential diagnosis of calcified intraarticular lesions in the young athlete. PMID- 1637444 TI - Arthroscopic-assisted glenohumeral arthrodesis. AB - A case of successful glenohumeral arthrodesis performed under arthroscopic control is presented. Clinical and radiographic fusion occurred by 6 weeks after the procedure. Salient features of the procedure include arthroscopic debridement of all hyaline cartilage and subchondral bone on both sides of the joint, reduction in a functional position, and internal fixation with percutaneously placed screws. PMID- 1637445 TI - Resection of bucket-handle meniscus tears: a simple technique using a Beaver blade. AB - This article describes a simple technique for the use of a #66 Beaver blade to assist in the resection of bucket-handle meniscus tears. This is a standard ophthalmologic blade and should be readily available in most operating rooms. The technique described is a simple, inexpensive means of resecting bucket-handle tears without changing portals during the procedure. PMID- 1637446 TI - The surgical approach to lateral meniscal repair. AB - Peripheral lateral meniscal tears are amenable to meniscal repair. Rasp abrasion and fibrin clot deposition along with vascular access channels are advances that, one hopes will increase healing rates of meniscal repairs. A basic principle that is not emphasized in the literature is how to perform the surgical approach to the lateral meniscus for safe placement of a meniscal repair retractor. This article reviews the anatomical planes of which the surgeon must be cognizant to facilitate retractor placement. PMID- 1637447 TI - [Value of MRT in diagnosis of tumors in the area of the temporal bone, nasopharynx, nose, paranasal sinuses and cranial aspects of the parapharyngeal space]. AB - Magnetic resonance imaging (MRI) is now an established technique which is becoming increasingly important in the diagnosis, treatment planning and follow up of ENT tumours. It offers numerous advantages over other diagnostic procedures, especially computed tomography (CT). The soft tissue contrast enabled by MRI is superior to that obtained with CT scanning. MRI also enables multiplane imaging, which facilitates evaluation of the complex anatomy of the head. Apart from spin echo sequences, the most commonly employed technique, gradient echo sequences are becoming ever more important. This technique is flow-sensitive, reduces the investigation time and permits 3D imaging. PMID- 1637448 TI - [Olfactory sensitivity in adenoid hyperplasia]. AB - Olfactory sensitivity was assessed in 37 children aged between 5 and 12 years before and after adenectomy. Olfactory detection thresholds for 2-phenylethanol and dimethyldisulphide, as well as the ability to distinguish 8 other odours, were measured using a squeeze bottle test. The results suggest that preoperative olfactory detection thresholds in subjects with severe nasal obstruction attributable to adenoid hypertrophy are higher than in those with less severe nasal obstruction. The olfactory detection thresholds improved after adenectomy in cases with high preoperative nasal obstruction indices. The olfactory detection threshold remained relatively unchanged in cases with less severe adenoid hyperplasia. In contrast, improvement in olfactory discrimination was observed in all children, irrespective of the degree of preoperative nasal obstruction. PMID- 1637449 TI - [Allergic rhinopathy: Magic Lite SQ Allergy Screen Inhalant and CAP-FEIA SX1- comparison of two allergen-specific screening tests in serum]. AB - Although total IgE determination in the diagnosis of allergic rhinitis has been proposed for screening, specific tests seem to be more efficient. In this study, Magic Lite SQ Allergy Screen Inhalant (ML) and CAP-FEIA Phadiatop (CF) were compared in serum in a group of 101 patients with allergic rhinitis (41 women, 60 men, mean age 31.4 years, range 7-69) and 37 controls (17 women, 20 men, mean age 38.3 years, range 6-68). All patients were suffering from nasal disease. The diagnosis based on case history, skin prick test, total and specific IgE determination and nasal challenge tests. ML was found to have a sensitivity of 96% and a specificity of 83.8% while CF achieved a sensitivity of 94.1% and a specificity of 94.6%. Efficiency was 92.8% for ML and 94.2% for CF. A positive predictive value of 94.2% for ML and of 97.9% for CF was calculated while the negative predictive value was 88.6% for ML and 85.4% for CF. It is concluded, that both ML and CF are suitable allergy screening tests able to give a 100% diagnostic security in combination with further examinations, especially regarding the case history. PMID- 1637450 TI - [Ozena and allergic rhinitis in ichthyosis vulgaris]. AB - The clinical course of an ozaena in a patient with an autosomal dominant ichthyosis vulgaris was complicated by the skin disease related atopic disposition with allergic rhinitis. Electron microscopic studies of the pathologically keratinized mucosa of the nasopharynx revealed a similar defect of the mucosal keratohyalin caused by the absence of the protein filaggrin. PMID- 1637451 TI - [Biopsy of the temporal artery in polymyalgia rheumatica]. AB - Biopsy of the temporal artery is still the most important component in the diagnosis of polymyalgia rheumatica and giant cell arteritis. Although this is a minor surgical intervention, certain vascular complications must be considered. Therefore, preoperative Doppler sonography should be performed. Finally, to prevent false-negative results, the temporal artery should be excised bilaterally and not shorter than 4 cm. PMID- 1637452 TI - [Esthetic aspects of excision of basaliomas of the area of the head and neck]. AB - Eighty-four patients with basal cell carcinoma of the head and neck were submitted to surgery. In 75%, infiltration of the reticular dermis or the subcutis was documented. Primary closure of the wound was achieved in only one third of these patients. In the remaining cases, the defects were closed by local flaps, regional flaps or a microvascular forearm flap. In 86% of the cases, good to-excellent results were achieved. PMID- 1637453 TI - [A recommendation for calibration and choice of masking noises used in speech audiometry]. AB - Tests to evaluate speech recognition ability against background noise have still not been adequately standardized. This is due in part to the lack of a calibration procedure for the various noises used in testing. In the present study, a psychoacoustic method for the calibration of fluctuating background noises was evaluated. Three types of noise were used: babble noise, stationary noise and fluctuating speech simulating noise in accordance with (CCITT Rec. G 227). Following calibration, the masking effect of each type of noise was evaluated. Results indicated that stationary and fluctuating speech simulating noise had similar effect on speech understanding ability. The steepness of the intensity-intelligibility function was significantly greater using babble noise as compared with stationary or fluctuating speech simulating noise. Babble noise was well accepted by our subjects. However, since its measurement can be calibrated, stationary speech simulating noise may also be used in speech audiometry. PMID- 1637454 TI - [Evoked otoacoustic emissions in diagnosis of cochlear hearing disorders]. AB - The authors consider the possibility of routine use of evoked otoacoustic emissions (EOE) in diagnosis of sensory hearing loss by comparison of EOE curves with relative curves obtained by pure tone audiometry. 180 ears with sensory hearing loss of different aetiologies were examined. EOE were obtained by application of Bray and Kemp's Evoked Otoacustic Measurement Package (ILO88). The results obtained show a close correlation between presence of EOE and real hearing losses of different frequencies obtained by pure tone audiometric evaluation. We could detect no EOE with hearing losses over 50 dB HL at 500 Hz, 40 dB HL at 1000 Hz, 50 dB HL at 2000 Hz and 85 dB HL at 4000 Hz. With a rate of middle hearing loss over 45 dB HL we also did not find EOE for the whole frequency range. On the base of this study, the authors conclude that EOE explore the functional integrity of those parts of the cochlea that correspond to the middle frequencies of hearing range. If EOE are not detectable, statements on the nature and extent of hearing loss on the base of this examination are not valid. PMID- 1637455 TI - [The temporal course of nystagmus reactions after rotational stimulation (modified Veits long rotational method). Part II. Recommendations for the simplification of nystagmus evaluation in the rotational test]. AB - In this study, on the basis of the graphics showing the time course of the nystagmus reactions following rotatory stimuli (Part I), some practical proposals are made on how the nystagmus responses following the rotatory test can be routinely analysed more quickly. The recommendations are oriented to the requirement that the selection of defined 30-second-intervals during the per- and postrotatory phase for the nystagmus analysis should reflect the total reaction in healthy subjects as well as in patients with acute vestibular lesions in a representative manner. It is also shown that reducing the analysis intervals to only 15 seconds or selecting unfavourable segments, can lead to an unacceptable falsification of the results. PMID- 1637456 TI - [Provocable tumor of the cheek as a manifestation of so-called "infiltrating lipoma" of the masseter muscle]. AB - We report on a 29-year-old male patient, who presented at our outpatient clinic with a 6-year history of progressive swelling of the right cheek. Contraction of the masseter muscle increased the swelling. MR-Imaging revealed a tumor measuring 2 x 3 cm, which was located within the masseter muscle. The histological diagnosis was infiltrating lipoma, which to our knowledge has not been described in this area before. This particular type of lipoma is extremely rare in the head and neck. The diagnostic and therapeutic management of infiltrating lipoma is discussed, and guidelines for adequate follow-up suggested. In addition, the authors review other sites of this tumor and describe its histological characteristics and differential diagnosis. PMID- 1637457 TI - [Paralysis of the hypoglossal nerve after bilateral tonsillectomy]. PMID- 1637458 TI - [Prevention of gagging in pharyngeal inspection]. PMID- 1637459 TI - Nurses and doctors ... and patients. AB - A Forum discussion group hosted by Dr Eilif Liisberg was formed from a few of the participants at a WHO nursing conference in Geneva. Subjects discussed were the status of nursing and changing attitudes to patients. PMID- 1637460 TI - "PolioPlus", a booster shot. PMID- 1637461 TI - Immunization: full coverage the aim. PMID- 1637462 TI - Postage stamps with WHO messages. PMID- 1637463 TI - Multilingual health education tapes project. PMID- 1637464 TI - Smaller health areas for a better service. AB - An analysis of Sudan's health system revealed a lack of sound leadership for village-level providers. The district-based peripheral health system was failing to meet an increased demand for leadership and management support. Some of the principal factors explaining this state of affairs were population growth, increased numbers of health units, long distances and transport difficulties. With a view to solving these problems, the country was divided into smaller health areas around rural hospitals and similar physician-led facilities. A decentralized system based on the principles of primary care was established in these areas under health area management teams. Setbacks encountered in giving effect to the policy have led to proposals for a new implementation strategy. PMID- 1637465 TI - Health systems in flux as East meets West. AB - The characteristics of health systems in eastern and western Europe and North America are outlined with special reference to financial control and accountability. The advantages and drawbacks of the various systems are examined and the prospects for new departures and improved services are considered. PMID- 1637467 TI - Homo sapiens--a suicidal species? PMID- 1637466 TI - Homo sapiens--a suicidal species? PMID- 1637468 TI - Health messages on postage stamps. PMID- 1637469 TI - Nursing education in Indonesia. PMID- 1637470 TI - Acupuncture and moxibustion in primary health care in rural China. PMID- 1637471 TI - Ancillary health workers, a resource worth cultivating. PMID- 1637472 TI - Health promotion on board ships. PMID- 1637473 TI - Schoolchildren as conveyors of health information for family members. PMID- 1637474 TI - Education: the key to preventing vesicovaginal fistula in Nigeria. PMID- 1637475 TI - Amnesty International is also concerned about health. PMID- 1637476 TI - Pharmacy education and drug abuse in Pakistan. PMID- 1637477 TI - Safe childbirth needs more than medical services. AB - This article reviews nonmedical factors contributing to maternal mortality in Indonesia, the Philippines, and Thailand. In general, countries or regions should define their own priorities for intervention strategies designed to diminish the influence of such factors. PMID- 1637478 TI - Birth kits for safe motherhood in Bangladesh. AB - Tetanus infection remains the leading cause of high neonatal mortality in Bangladesh. Birth kits which instruct and assist in a clean, safe birth are seen as a key measure in reducing the high incidence of neonatal deaths. A multisectoral programme has developed a simple kit and tested its potential for distribution to pregnant women. Initial results are positive and development is continuing. PMID- 1637479 TI - Prices for a leaner dairy industry. AB - For several decades, the basic policies of the dairy industries in developed countries, especially Canada and the Member States of the European Community, have encouraged the production of fat and have tended to neglect that of protein and minerals. This not only opposes the general well-being and the best interests of consumers but also distorts world trade. Much could be done by health professionals to persuade the milk producers, consumers and governments that support for dairy farming should be modified so that less fat and more protein are produced and consumed. PMID- 1637480 TI - Safer sex in tourist resorts. AB - A survey in Torbay, England, indicated substantial sexual interaction of an unsafe kind between young residents and tourists. A pilot programme is described which sought to promote safer sexual behaviour: the attention of both tourists and local people who frequented nightclubs was engaged by peer groups who conveyed educational messages. PMID- 1637481 TI - What choices in care for the incontinent? AB - Urinary and faecal incontinence affect many millions of people yet much remains to be done before they can all be properly cared for and the incidence of the conditions can be significantly diminished. The author discusses the situation in the light of a comparison of nursing initiatives in Denmark and the United Kingdom. PMID- 1637482 TI - New AIDS strategy aimed more at women. PMID- 1637483 TI - Global AIDS update. PMID- 1637484 TI - Children's vaccine initiative. PMID- 1637485 TI - [Atopic dermatitis. Epidemiology]. AB - It was in 1923 that Coca and Cooke made a distinctive entity of a group of diseases of allergy, including asthma, and hay fever. They remarked that these affections were frequently associated and/or preceded by eczema localised to certain regions (flexor folds), sometimes generalised, perhaps appearing suddenly, from the third month in infants. In effect, the majority of constitutional eczema is in infants of 6 months, 75% of the cases are in one-year old children. There is recovery in 5 years following the start of the affection in 90% of cases. Only 5% of cases persist to adulthood. PMID- 1637486 TI - [Clinical diagnosis of atopic dermatitis]. AB - Atopic eczema is a pruriginous dermatosis that most often starts before one year, but which may show for the first time after 50 years. The diagnosis is essentially clinical, with signs of banal eczema (especially acute in young infants, more chronic later) but of which the topography develops characteristically as a function of age and in the context of atopy. The development of is chronic, dotted with inflamed eruptions and may be complicated by an alteration of general state with bacterial (very frequent) or viral superinfections. The appearance of asthma is frequent when the dermatosis is extended. It usually disappears before adult age. Differential diagnosis is needed especially when there is an atypical form or association with another pruriginous dermatosis. Questioning must cover the environment, food habits and search for signs that may show the responsibility of an allergen. PMID- 1637487 TI - [Etiologies of atopic dermatitis]. AB - Atopic dermatitis is no longer a constitutional illness that cannot be influenced. The discovery of IgE fixed to the cells of Langerhans changes the physiopathological concept of this illness. There must be a minutely careful search for all the possible etiologies before advising therapy or long-term treatment. Attention must be given to the role of foods, discovery of causal pneumoallergens and a systematic search for a contact allergen must be made. This systematic and scrupulous search also gives confidence to a patient who is discouraged by the development of the condition. PMID- 1637488 TI - [Complementary examinations in atopic dermatitis]. AB - The complementary assessment of atopic eczema involved a biological assessment: one part in vitro (total IgE, specific IgE, T4/T8 immunoregulator index); one part in vivo (skin tests: skin reaction intradermal reaction, patch test). PMID- 1637489 TI - [Treatments for atopic dermatitis]. PMID- 1637490 TI - Anxiety and family needs of the relatives of cardiac medical-surgical ICU patients. AB - The purpose of this study was to seek information on the perceived needs of family members visiting a patient in a critical care unit (ICU) of two hospitals located in Sudbury, Ontario. The sample included fifty-one family members visiting cardiovascular surgical patients (CVS) and forty-four family members visiting cardiovascular medicine patients (CVM). The study was part of a larger project conducted on a convenience sample of 166 subjects visiting an ICU patient. Data was gathered using a self-report questionnaire, the Critical Care Family Needs Inventory (CCFNI) (Molter and Leske, 1983), and Spielberger's (1983) State Trait Anxiety Inventory (STAI). Information was also collected about worries, knowledge, spiritual needs and the distance of subjects' residence from the site of hospitalization. The sample for both groups was predominantly female. The State Anxiety Scale of the STAI yielded mean scores for both groups which were significantly higher than those obtained by Spielberger (1983) (CVS: z = 3.28, p less than .0001; CVM: z = -3.41, p less than .0001). PMID- 1637491 TI - Delay in seeking appropriate medical help by individuals experiencing the symptoms of heart attack. PMID- 1637492 TI - Policy, practice and research. PMID- 1637493 TI - A community survey of cardiac emergency skills: symptom recognition and CPR. AB - This descriptive study assessed recognition of symptoms of myocardial infarction (MI) by community members and their ability to respond to emergency situations with cardiopulmonary resuscitation (CPR) skills. One thousand questionnaires were randomly mailed to residents with a response rate of 48.1%. Results indicated that residents have limited awareness of symptoms of MI other than demonstrated chest pain and that 20.6% of the respondents had taken a CPR course. CPR courses were taken by 9.6% of respondents who had one or more relatives diagnosed with heart disease. The lack of awareness of symptoms of MI and limited ability to perform CPR skills in emergency situations by community residents may contribute to the high mortality rates due to heart disease. Results of the study suggest that educational campaigns be instituted in the community under study to promote recognition of and response to cardiac emergencies. PMID- 1637494 TI - The effect of prenatal ethanol exposure on scentmarking in the C57BL/6J and C3H/He mouse strains. AB - In utero exposure to ethanol has been shown to alter sexually dimorphic behaviors in rats. However, it is not clear whether this phenomenon is robust in other species, such as the mouse, which is sensitive to ethanol-induced birth defects. Further, it is not known whether significant differences exist across murine strains. If similar to the classic teratogenic effects of ethanol, it would be expected that strain differences in sensitivity should be evident, with some strains demonstrating an alteration in sexually dimorphic behavior and other strains demonstrating little or no effect. As a first attempt to address these issues, we have examined two mouse strains widely used in prenatal alcohol research, the inbred C3H/He and C57BL/6J strains. Scentmarking was selected as the behavior of interest. It is robustly sexually dimorphic in the rat and mouse, with males marking more than females and preliminary reports have demonstrated that in utero ethanol exposure reduces this behavior in the male rat. In the mouse strains selected for study, pregnant females were provided with either a liquid diet consisting of 25% ethanol-derived calories or pair-fed an isocaloric liquid diet from gestation days 6-18. An additional control group was included which was fed laboratory chow ad lib throughout gestation. Male and female offspring of each strain were tested for scentmarking at 65-75 days of age. As expected, results showed that the effect of prenatal ethanol exposure on scentmarking varied with both strain and sex. In the C3H/He strain, scentmarking was reduced significantly in male ethanol-exposed offspring (i.e., the males were feminized).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637495 TI - Rat synaptic membrane fluidity parameters after intermittent exposures to ethanol in vivo. AB - Differentiated membrane alterations correlate with the development of functional tolerance or dependence during chronic alcohol intoxication in humans as well as in animals. In animal studies, a single period of continuous exposure was generally used. In humans, the consumption can be more episodic with heavier weekend drinking. How a heavy but intermittent alcohol exposure over 4 weeks affects the synaptic membrane fluidity and sensitivity was examined in male and female adult rats. No differences were seen between membranes from males and females. Alterations were found in the negative polar membrane region probed by TMA-DPH and the sensitivity to acute ethanol was significantly reduced in the DPH (lipid core) and TMA-DPH probed membrane regions. Tolerance to the hypothermic effect of ethanol has developed and could be correlated with the resistance of the membrane lipid core to ethanol. Intermittent exposures to ethanol, as continuous ones, can result in development of functional and membrane tolerance and in specific alterations in the fluidity of the polar part of the membrane, probably in relation with dependence. PMID- 1637496 TI - Cardiorespiratory reflex due to pulmonary J receptors stimulation by acetaldehyde in rats. AB - Acetaldehyde (AcH) administered intravenously or into the right ventricle induces reflex bradycardia, hypotension, and apnea in the rat. The efferent pathway for this reflex is vagal and probably secondary to pulmonary J receptors stimulation. Located between the alveoli and the pulmonary capillary, J receptors are accessible through the pulmonary circulation and the airways. For this reason, a method for indirect nebulization (IN) of AcH into the airways, that provides a continuous record of respiration without changes in intrapulmonary pressure, was developed. IN of AcH (n = 14) induced bradycardia (64 +/- 3.1%), hypotension (34 +/- 4.2%), and apnea (79%), which were blocked by vagotomy (n = 9). The latencies (s) for bradycardia (0.34 +/- 0.06), hypotension (0.68 +/- 0.11), and apnea (0.25 +/- 0.11) were significantly shorter than those obtained by the intravenous route. Three rats that did not develop apnea had an equivalent response, where both tidal volume and minute ventilation decreased about 40% and these effects were also blocked by vagotomy. Indirect nebulization of AcH allowed us to demonstrate that pulmonary J receptors are responsible for this reflex response. PMID- 1637498 TI - A role for behavioral sensitization in uncontrolled ethanol intake. AB - The processes that underlie the transition from controlled to uncontrolled consumption of ethanol are unknown. Behavioral sensitization is proposed as one of these processes and occurs with repeated administration of psychomotor stimulants whereby both behavioral and neurochemical responses to the drugs are progressively enhanced. Because ethanol shares some actions in common with these drugs, chronic exposure to ethanol may intensify its reinforcing properties. The effect of ethanol on several behavioral models suggests that behavioral sensitization may develop especially in the presence of environmental cues. Thus, a research opportunity exists to study factors that contribute to an increasing probability of progressively higher ethanol consumption. Knowledge of these factors will lead to a better understanding of why some people drink uncontrollably. PMID- 1637497 TI - Ceramide composition of whole brain synaptosomal gangliosides from mice genetically bred for divergent ethanol sensitivities. AB - A comparison of the two major ceramide molecular species (d18:1-C18:0 and d20:1 C18:0) of synaptosomal gangliosides GM1, GD1a+GT1a, GD1b, GT1b, revealed a difference between the ceramide composition of ethanol-sensitive LS and ethanol insensitive SS whole brain synaptosomal gangliosides. In all comparisons, the ratio of the two major molecular species, (d18:1-C18:0/d20:1-C18:0) was less for LS than for SS mice. PMID- 1637499 TI - Effect of chronic consumption of ethanol and vitamin E on fatty acid composition and lipid peroxidation in rat heart tissue. AB - Lipid peroxidation products and the fatty acid composition of phospholipids were studied in the hearts of rats chronically consuming ethanol supplemented with large amounts of vitamin E. Ethanol representing 36% of the total calories was ingested for 7 weeks in a modified Lieber-DeCarli liquid diet that contained vitamin E at 30 IU/L in the control or 172 IU/L in the supplemental dietary group. Ethanol and/or vitamin E did not change the absolute content (micrograms per mg of phospholipids) of the main fatty acids (C18:0, C18:2, and C20:4) of heart phospholipids but increased the amount of the minor C20-C22 fatty acids. Cardiac phospholipid levels increased in rats chronically consuming excess vitamin E and/or alcohol. Chronic ethanol consumption caused elevations of the relative content (percent of total fatty acids) of tri-, tetra-, and hexaenoic acids and peroxidizability index (PI) of the cardiac phospholipids. Supplementation with vitamin E blocked this ethanol-induced shift in the fatty acid profile toward unsaturation and decreased the PI. Ethanol enhanced accumulation of vitamin E in heart tissue by 30% irrespective of the vitamin E content in the diet. Enrichment of the diet with vitamin E coincided with the low levels of fluorescent products in heart lipids. A positive correlation (r = 0.36; p = 2%) was found between vitamin E and diene conjugates in the heart cells. Thus, vitamin E has a stabilizing effect on heart phospholipids by preventing changes in their fatty acid composition and peroxidative deterioration. PMID- 1637500 TI - Delayed onset of puberty and subtle alterations in GnRH neuronal morphology in female rats exposed prenatally to ethanol. AB - Fetal alcohol exposed (FAE) animals exhibit physiological and behavioral deficits associated with reproduction including alterations in LH secretion and decreased sex behavior. Such deficits led us to examine the morphological characteristics and number of GnRH neurons in female rats prenatally exposed to ethanol. Sprague Dawley dams (Harlan, Indianapolis, IN) were administered a fortified liquid diet (Sustacal) containing 35% ethanol derived calories from day 7 through parturition. Controls were pair-fed a similar isocaloric diet containing no ethanol during this period or allowed access to dry food pellets ad lib. Compared to both control groups, puberty was found to be significantly delayed in females that were exposed prenatally to ethanol. The median age of vaginal opening for chow-fed and pair-fed controls was 34-35 days compared to 38-39 days for FAE animals. A subgroup of these females was selected at 44 days of age on the basis of delayed onset of puberty and compared with pair-fed controls for the number and morphology of GnRH-immunoreactive staining (ir) neurons in the medial preoptic area (MPOA) and the diagonal band of Broca (DBB), regions which contain the majority of GnRH-IR cells in the rat brain. In both areas, light microscopic study revealed no differences in GnRH-IR cell number, nor were differences detected among the groups in the number of bipolar versus unipolar cells. However, a significant increase was observed in FAE brains compared to controls in the ratio of GnRH-IR neurons with irregular processes compared to smooth cell contours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637501 TI - Activated conformations of the ras-gene-encoded p21 protein. 1. An energy-refined structure for the normal p21 protein complexed with GDP. AB - A complete three-dimensional structure for the ras-gene-encoded p21 protein with Gly 12 and Gln 61, bound to GDP, has been constructed in four stages using the available alpha-carbon coordinates as deposited in the Brookhaven National Laboratories Protein Data Bank. No all-atom structure has been made available despite the fact that the first crystallographic structure for the p21 protein was reported almost four years ago. In the p21 protein, if amino acid substitutions are made at any one of a number of different positions in the amino acid sequence, the protein becomes permanently activated and causes malignant transformation of normal cells or, in some cell lines, differentiation and maturation. For example, all amino acids except Gly and Pro at position 12 result in an oncogenic protein; all amino acids except Gln, Glu and Pro at position 61 likewise cause malignant transformation of cells. We have constructed our all atom structure of the non-oncogenic protein from the x-ray structure in order to determine how oncogenic amino acid substitutions affect the three-dimensional structure of this protein. In Stage 1 we generated a poly-alanine backbone (except at Gly and Pro residues) through the alpha-carbon structure, requiring the individual Ala, Pro or Gly residues to conform to standard amino acid geometry and to form trans-planar peptide bonds. Since no alpha-carbon coordinates for residues 60-65 have been determined, these residues were modeled by generating them in the extended conformation and then subjecting them to molecular dynamics using the computer application DISCOVER and energy minimization using DISCOVER and the ECEPP (Empirical Conformational Energies for Peptides Program). In Stage 2, the positions of residues that are homologous to corresponding residues of bacterial elongation factor Tu (EF-Tu) to which p21 bears an overall 40% sequence homology, were determined from their corresponding positions in a high-resolution structure of EF-Tu. Non-homologous loops were taken from the structure generated in Stage 1 and were placed between the appropriate homologous segments so as to connect them. In Stage 3, all bad contacts that occurred in this resulting structure were removed, and the coordinates of the alpha-carbon atoms were forced to superimpose as closely as possible on the corresponding atoms of the reference (x-ray) structure. Then the side chain positions of residues of the non-homologous loop regions were modeled using a combination of molecular dynamics and energy minimization using DISCOVER and ECEPP respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1637502 TI - Molecular dynamics simulation in vacuo and in solution of [Aib5,6-D-Ala8] cyclolinopeptide A: a conformational and comparative study. AB - The conformation of a Cyclolinopeptide A analogue, c-(Pro-Pro-Phe-Phe-Aib-Aib-Ile D-Ala-Val), has been investigated by means of molecular dynamics simulations, in various molecular environments. The molecular dynamics results are compared with that obtained for Cyclolinopeptide A and a detailed analysis of the different behaviour for the two compounds is reported. A complete analysis of hydrogen bonds is presented. PMID- 1637503 TI - The structures of bacteriorhodopsin with different retinal-Schiff base orientations--computer modeling and energy minimization studies. AB - Bacteriorhodopsin has been the subject of intense study in order to understand its photochemical function. The recent atomic model proposed by Henderson and coworkers based on electron cryo-microscopic studies has helped in understanding many of the structural and functional aspects of bacteriorhodopsin. However, the accuracy of the positions of the side chains is not very high since the model is based on low-resolution data. In this study, we have minimized the energy of this structure of bacteriorhodopsin and analyzed various types of interactions such as -intrahelical and interhelical hydrogen bonds and retinal environment. In order to understand the photochemical action, it is necessary to obtain information on the structures adopted at the intermediate states. In this direction, we have generated some intermediate structures taking into account certain experimental data, by computer modeling studies. Various isomers of retinal with 13-cis and/or 15-cis conformations and all possible staggered orientations of Lys-216 side chain were generated. The resultant structures were examined for the distance between Lys-216-schiff base nitrogen and the carboxylate oxygen atoms of Asp-96- a residue which is known to reprotonate the schiff base at later stages of photocycle. Some of the structures were selected on the basis of suitable retinal orientation and the stability of these structures were tested by energy minimization studies. Further, the minimized structures are analyzed for the hydrogen bond interactions and retinal environment and the results are compared with those of the minimized rest state structure. The importance of functional groups in stabilizing the structure of bacteriorhodopsin and in participating dynamically during the photocycle have been discussed. PMID- 1637504 TI - Nucleic acids packaging processes: effects of adenine tracts and sequence dependent curvature. AB - The effects of short runs of adenines (A-tracts) upon nucleic acids packaging processes and the properties of the resulting condensates were investigated by using random DNA sequences isolated from natural sources, as well as synthetic segments obtained by an extensive ligation of specific oligomers. Reiteration of short A-tracts (A(N) where N less than 3) within the DNA molecules is found to be compatible with a long-range chiral organization of the strands in the nucleic acid condensed phases. This chiral order, whose occurrence necessitates a high degree of flexibility, is shown, however, to differ from that exhibited by packed species originating from random AT-rich fragments; the altered patterns are interpreted in terms of a reduced overall flexibility of the DNA strands. Repetition of longer A-tracts (where N greater than 3), in which the distinct structural features that characterize this motif are fully expressed, results in a complete suppression of any chiral order in the packed particles, assigned to a significantly enhanced rigidity. DNA fragments where A-tracts are reiterated in phase, leading to a stable macroscopic curvature, are found to undergo condensation through altered pathways and to form toroidal shapes of unusually small dimensions. The results point towards the intriguing possibility that A tracts and, in particular, the global, intrinsic curvature associated with such motifs, might be involved in the determination of nucleic acids packaging pathways, and underline the usefulness of defined sequences in the study of DNA condensation processes. PMID- 1637505 TI - Preferred positions of AA and TT dinucleotides in aligned nucleosomal DNA sequences. AB - Multiple alignment of 118 nucleosomal DNA sequences by maximizing simultaneously match of AA dinucleotides and match of TT dinucleotides results in a pattern of the dinucleotide distributions which is characteristic of the nucleosomal DNA sequences. The AA dinucleotides are found to be distributed symmetrically relative to the TT dinucleotide distribution, around the middle point of the nucleosomal DNA sequence. The distances between major peaks of the distributions are multiples of about 10.4 bases. The peaks of the TT distribution are shifted by 6 bases downstream from the peaks of the AA distribution. PMID- 1637506 TI - Molecular modeling to predict the structural and biological effects of mutations in a highly conserved histone mRNA loop sequence. AB - The 3'-end of histone mRNAs contains a highly conserved sequence motif which is believed to form a 6 base pair stem and a 4 base loop. These sequences are involved in both the efficiency of 3'-end formation and stability of the mature histone mRNA. We have modeled four stem basepairs and the loop portion of this structure using the wildtype sequences and several mutant sequences. A structure for the wildtype stem-loop is proposed that is based on energy minimization using a representative wildtype sequence and comparison with structures obtained using naturally occurring mutations which do not alter loop function. A wildtype structure is proposed in which the top basepair of the stem is broken, forming a six base loop. Mutant sequences with altered bases in the loop and in the stem were also modeled. The effect of these mutations on the proposed wildtype structure is discussed and possible biological consequences considered. PMID- 1637507 TI - Base sequence criteria and Cartesian coordinates for stable B/Z and B/Z/B junctions in relaxed DNA. AB - It seems increasingly evident that if the Z form of DNA exists in the genome it must exist as short sections of alternating pyrimidine-purine sequences in the midst of very long sections of B-form DNA. We have determined the minimum length of a string of alternating CG base pairs that can go into the Z form in the middle of a long B form. Self-complimentary oligomers of the form T(M)(CG)(N)A(M) were synthesized. The conformation of the resulting duplex was determined in 6M aqueous NaCl solution by Raman scattering. We have found that 12 alternating CG base pairs is the minimum length required to form a stable Z form of DNA inside of a long B form section. Only the 4 center CG base pairs go into the Z form. These 4 CG base pairs in the Z form are flanked on each side by 4 CG base pairs in a non-Z (probably B) form as well as the ..TT.. ..AA.. sequences in the B form. We propose a model of the B/Z junction in which the double helix flips directly from the B form to the Z form so that there are no base pairs in the junction. In this model the B form is nucleated in the AT base pairs on each end and is propagated into the CG base pairs in the center. This model is supported by isotopic H/D exchange experiments that shows that the H/D exchange of the non Z form CG base pairs is highly retarded and indicates that they remain in the B form. A Thermodynamic analysis of the concentration dependence of the melting point of the duplexes in both low and high salt, supports our model and rules out the possibility of hairpin formation. The enthalpy for the formation of a B/Z junction is determined to be about +16 kcal/junction. A comparison of these results with recent results on B/Z junctions in super-coiled DNA is given. Molecular modeling calculations permit us to obtain values for the coordinates and torsional angles of the oligomers showing both B/Z and B/Z/B junctions. The Cartesian coordinates for these oligomers as well as stereo figures of these models in color are available from the authors. PMID- 1637508 TI - A reduced set of coordinates for modeling DNA structures: (I). A B-to-A transition pathway driven by pseudorotational angle. AB - The A-DNA and the B-DNA are two well characterized polymorphous forms of DNA duplex. By using Metropolis Monte Carlo Simulations in a reduced coordinate space, we have shown that the B in equilibrium with A transitions can be induced by forcing pseudorotational angle (W) to change between C3'-endo and C2'-endo puckerings. The energy barrier for the transition pathway is less than 10 Kcal.mol-1. Base-pair parameters x-displacement (Dx) and roll (rho), which have the largest differences between the two forms of structures, cannot drive the transition. Our results support the view that the bistable states of the DNA duplex are due to the bistable structures of the sugar ring. PMID- 1637509 TI - Sequence effects on the propeller twist of base pairs in DNA helices. AB - Molecular mechanics calculations are performed on all the ten base pair steps (duplex dimers) and also a number of trimer and tetramer duplexes comprising them, in an attempt to systematically examine the possible base sequence effects on the magnitudes of propeller twists of base pairs at a given step. The analysis reveals that though propeller twist is a base pair property, it behaves very much like other base step parameters such as slide, roll, twist etc., Hence, it may be necessary to monitor the nature and variation of magnitudes of pt at a step. Calculations performed on 45 out of the 136 unique tetramer combinations involving all the ten unique base steps show that the difference in magnitudes of propeller twists of the base pairs of a given step has been found to be either steep or moderate depending on base pairs that flank the base step. These observations compare very well with the available experimental data. Tetramer sequences, wherein a base pair of a base step repeats in the same direction, exhibit a relatively steep difference in propeller twist at the step. Tetramers other than these exhibit moderate difference in propeller twist. Such sequences are broadly classified as type-I and type-II respectively. Practically all the tetrads considered in the study, excepting those with GT step and a few involving CG and GC steps, conform to the above classification. PMID- 1637510 TI - DNA sequences at and between the GC and TATA boxes: potential DNA looping and spatial juxtapositioning of the protein factors. AB - Regulation of gene expression in eukaryotes involves a complex assembly of DNA recognition sequence elements and their respective protein factors. The upstream promoter/enhancer sequences are position and orientation independent. Despite their variable distances from the TATA box and transcription start site, interaction between the protein activators and TATA general transcription factors takes place, enabling induced levels of transcription initiation. Here the intervening sequences between the GC and TATA boxes are examined as functions of their lengths. Regardless of the substantial differences in the spacer sizes, similar mono and dinucleotide distributions are noted. Purine-purine base pair steps, except for AA, are more frequent at and near the GC box in the 5' ends of the loops than in their 3' ends. Pyrimidine-pyrimidine base pair steps, except for TT behave similarly. AT and TA (as well as AA and TT) are more frequent in the 3' ends of the loops near the TATA. Examination of these distributions, as well as of the sequences composing the GC and TATA boxes indicates that the DNA in the upstream part of the loop is more rigid, whereas the downstream regions are far more flexible. The flexibility of the general TATA region may afford correct spatial juxtapositioning of the proteins with respect to each other, enabling interactions between the activators and the general transcription factors. PMID- 1637511 TI - A Monte Carlo simulation of hydration of xanthine-derivatives and their stacked forms. AB - Results on a Monte Carlo simulation of the hydration of monomer and possible stacked dimer forms of a purine alkaloid series in 200- and 400-water molecule clusters are presented. Investigation of different purine stacked dimers in a 200 water molecule cluster reveals that for caffeine there exists one, for theophylline two and for theobromine four dimers are energetically favorable. For caffeine, the same energetically favored stacked dimer form is observed in both the 200- and 400-water molecule cluster. The main factor stabilizing the preferred dimer stacks is the change in the interaction between water molecules of the monomer cluster and those water molecules in the dimer cluster. PMID- 1637512 TI - The conformational behaviour of complexes of alpha-cyclodextrin with p chlorophenol and p-hydroxybenzoic acid in water as studied by molecular dynamics simulations. AB - Molecular dynamics simulations were performed to obtain information about the conformational behaviour and stabilization of alpha-cyclodextrin (alpha CD) complexes in water. Simulations of p-chlorophenol and p-hydroxybenzoic acid in alpha CD showed that the complex is a very flexible system. The guest compound rotates inside the cavity and partly moves in and out. alpha CD continuously adapts its conformation to the orientation of the guest compound (or vice versa): the hexagon of the glycosidic oxygen atoms is stretched parallel to the plane of the aromatic ring of the guest compound during 80% of the simulation. This suggests that Van der Waals interactions play an important role in the stabilization of the complex. Each intramolecular hydrogen bond between neighbouring glucose units is formed during 30-80% of the simulation. Hydrogen bonds between alpha CD and the guest compound, on the other hand, are rarely formed. Thus, intermolecular hydrogen bonding seems to play a minor role in the stabilization of alpha CD complexes. PMID- 1637513 TI - Effect of enalapril on the progression of chronic renal failure. A randomized controlled trial. AB - In order to study the influence of angiotensin converting enzyme (ACE) inhibition on the progression of chronic nephropathy, 70 patients with a median glomerular filtration rate (GFR) of 15 (range, 6 to 54) mL/min/1.73 m2 were randomized in an open study to basic treatment with enalapril or conventional antihypertensive treatment. The patients were followed for at least 2 years or until they needed dialysis. The groups were comparable with respect to age and sex distribution, etiology of renal diseases, initial levels of renal function and arterial blood pressure (BP), and protein intake. The therapeutic goal was a BP of 120 to 140/80 to 90 mm Hg. The GFR, estimated by the plasma clearance of 51Cr-EDTA, was measured every third month, and the individual rate of progression was calculated as the slope of the GFR v time plot. In the enalapril group, the median decline in GFR was -0.20 (range, +0.18 to -7.11) mL/min/1.73 m2/month and in the control group it was -0.31 (+0.01 to -1.97) mL/min/1.73 m2/month (P less than .05). There was no significant difference in blood pressure or plasma lipid levels between the groups. Thus, the progression of moderate to severe chronic nephropathy was slower on a basic treatment with enalapril as compared to conventional antihypertensive therapy. PMID- 1637514 TI - Renal resistive index after captopril test by echo-Doppler in essential hypertension. AB - In 45 patients with essential hypertension and 15 age-matched normotensive control subjects, the renal resistive index, as an expression of arterial impedance, was determined using Doppler ultrasound. In both kidneys the resistive index was assessed at baseline and after captopril test (50 mg orally). In the moderate and severe hypertensives, compared to mild hypertensives and control subjects, the baseline resistive index was significantly higher (P less than .05). Following captopril, the resistive index increased only in normotensives (P less than .05) and in mild hypertensives (P less than .05). Univariate and multivariate analyses show that the duration and severity of hypertension correlated with an increase of the resistive index both in basal and in dynamic conditions. Thus, the use of the resistive index, as determined by echo-Doppler, could provide useful information for the assessment of renal vascular impedance in essential hypertensive patients. This would help us detect the evolution of hypertensive disease to the higher degrees of severity that are correlated to renal arteriolar damage. PMID- 1637515 TI - Beneficial effect of nifedipine and moxonidine on glomerulosclerosis in spontaneously hypertensive rats. A micromorphometric study. AB - The effect of calcium channel blockers on the development of glomerulosclerosis and progression of renal failure in different models of renal injury is still controversial. We compared the effects of blood pressure lowering with high doses of nifedipine (27 mg/kg body weight/day) and with the sympatholytic agent moxonidine (8 mg/kg body weight/day) in 6-month-old male spontaneously hypertensive rats (SHRsp). As controls we studied untreated hypertensive SHRsp and normotensive Wisfar-Kyoto rats (WKY). After 3 months of treatment, left ventricular (LV) weight and systolic blood pressure (tail plethysmography) were lower in both treated groups (144 +/- 21.4 mm Hg and 144 +/- 13.5 mm Hg v 193 +/- 38.6 mm Hg in untreated SHRsp), but remained higher than in WKY (116 +/- 16.0 mm Hg). Stereological analysis of perfusion fixed kidneys showed an unchanged total volume of cortex and medulla, but a higher mean glomerular volume in nifedipine treated SHRsp. The glomerulosclerosis index was similarly reduced by both antihypertensive agents (92.8 +/- 68.1 in untreated SHRsp v 27.2 +/- 12.9 and 18.2 +/- 9.8 in the two treatment groups, respectively). This was accompanied by a similar reduction of total cortical arterial wall volume (from 36.3 +/- 16.5 mm3 to 18.9 +/- 2.53 and 15.3 +/- 2.53 mm3, respectively) and by reduction of tubular atrophy or interstitial fibrosis, respectively. In this model nifedipine lowered blood pressure and inhibited development of glomerulosclerosis to the same extent as a sympatholytic agent. This was accompanied by increased glomerular volume and filtration area in nifedipine treated animals. PMID- 1637516 TI - Insulin resistance and abnormal electrocardiograms in patients with high blood pressure. AB - Plasma glucose and insulin responses to an oral glucose challenge and fasting plasma lipid and lipoprotein concentration were compared in 25 normal individuals and 53 patients with high blood pressure. Patients with hypertension were further subdivided into two groups--normal electrocardiogram (EKG) (n = 24) or abnormal EKG (n = 29)--using the Minnesota code criteria. Patients with hypertension and an abnormal EKG had significantly higher plasma glucose and insulin concentrations following oral glucose than did the control population. Furthermore, plasma triglyceride (TG) concentration was higher and high density lipoprotein cholesterol concentration lower then normal in hypertensive patients with an abnormal EKG, and the ratio of total to HDL cholesterol was higher in this subgroup. Values for patients with high blood pressure and a normal EKG were intermediate. Insulin-mediated glucose uptake was also measured in a subset of patients with hypertension and either a normal (n = 18) or abnormal (n = 17) EKG. When these two subgroups were compared, those with high blood pressure and an abnormal EKG were significantly more insulin resistant than patients with hypertension and a normal EKG. In addition, they also had higher plasma glucose and insulin responses to oral glucose, higher fasting plasma triglyceride and cholesterol concentrations, and an increase in the ratio of total to HDL cholesterol. Thus, patients with high blood pressure have abnormalities of glucose, insulin, and lipid metabolism when compared to a nonhypertensive control group, and the magnitude of these metabolic defects is significantly greater in patients with high blood pressure who have EKG evidence of coronary heart disease. PMID- 1637517 TI - Components of blood pressure variability in the elderly and effects on sample size calculations for clinical trials. AB - This study investigated components of blood pressure variability in the elderly using both ambulatory blood pressure monitoring (ABPM) and casual clinic blood pressure measurement. These were then used to determine sample size requirements for clinical trials of different design scenarios in the elderly. Twenty-six elderly subjects not receiving antihypertensive medication were recruited from general practices and seen on four occasions at weekly intervals. On each occasion of blood pressure was measured in the clinic using a standard mercury sphygmomanometer and then for 24 h using a noninvasive ambulatory monitoring device. The between subject and between subject/within occasion components of blood pressure variability were determined by analysis of variance and used to calculate to sample size requirements for parallel and crossover trials respectively. The between subject variance of mean blood pressure was 1/3 greater with clinic readings, except within a subgroup of subjects who had isolated systolic hypertension (ISH). Increasing the number of readings or occasions on which measurement was performed in a parallel group trial only reduced the variability substantially when the number of subjects involved was small. With crossover designs, the between subject component of variance is eliminated resulting in substantial reduction in sample size. Whereas 60 subjects with ISH would be required to detect a 10 mm Hg difference in systolic blood pressure between two treatments in a parallel design using casual readings, only 18 are required with a crossover trial. If ABPM is used the number of subjects required are 54 and 14, respectively. Reducing variability with ABPM involves a trade-off between the increased number of readings available with the technique against the highly uniform and standardized conditions used to determine clinic blood pressures. ABPM appears most useful as a strategy for reducing sample size in parallel group trials involving small numbers of subjects measured on one occasion. PMID- 1637518 TI - Cytosolic calcium and insulin resistance in elderly patients with essential hypertension. AB - We evaluated insulin sensitivity in normotensive (blood pressure, BP, less than 135/85 mm Hg) and hypertensive (BP greater than 160/90 mm Hg) elderly subjects over 65 years old who were stratified as normal weight (body mass index, BMI, less than 27) and obese (BMI greater than 27). Obese hypertensive individuals demonstrated marked hyperinsulinemia (P less than .01) and significantly reduced (P less than .05) submaximally stimulated adipocyte 2-deoxyglucose (2-DOG) uptake (abdominal wall fat biopsy). Normal weight hypertensive subjects also demonstrated higher levels of insulinemia and lower insulin-stimulated 2-DOG uptake than nonobese controls. Adipocyte [Ca2+]i levels were elevated in all elderly subjects compared to young individuals (P less than .01). Basal and maximally stimulated 2-DOG uptake were similar in all groups. One month of therapy with a calcium channel blocker, 10 mg nitrendipine twice daily, reduced blood pressure in the hypertensive subjects, reduced plasma insulin to control values during an oral glucose tolerance test in obese hypertensive individuals (P less than .01), and restored adipocyte 2-DOG uptake at submaximally effective insulin concentration to control values in normal weight and obese hypertensive subjects. In summary, older hypertensive, and particularly older obese hypertensive, patients manifest significant insulin resistance accompanied by elevated levels of [Ca2+]i in their adipocytes. PMID- 1637519 TI - Diagnostic accuracy of exercise thallium-201 scintigraphy in men with asymptomatic essential hypertension. AB - Coronary artery disease is responsible for much of the morbidity and mortality in patients with essential hypertension, and these complications have proven to be relatively resistant to antihypertensive therapy. However, the diagnosis of coronary disease in the hypertensive population has been considered problematic. In the present study, 30 asymptomatic patients with mild to moderate hypertension with positive exercise electrocardiograms (ECG) or stress thallium-201 scintigrams underwent coronary angiography to determine the accuracy of these tests for coronary artery disease. The exercise ECG was positive in 25 subjects, of whom 15 had significant coronary lesions and 10 did not. Thallium-201 scintigraphy proved more accurate: 17 of 18 patients with reversible abnormalities had significant obstructive coronary disease anatomically corresponding to the defect, one patient with a fixed defect had normal coronary arteries and was found to have an idiopathic cardiomyopathy, and 9 of 11 without defects had no significant lesions. The results were similar in populations with and without echocardiographic criteria for left ventricular hypertrophy. These findings indicate that despite previous suggestions to the contrary, thallium-201 scintigraphy can accurately diagnose coronary artery disease in most patients with asymptomatic essential hypertension, and that most asymptomatic hypertensive patients with physiologic evidence of myocardial ischemia have associated coronary artery disease. PMID- 1637520 TI - Effects of dietary fish oil on Rb+ efflux from aorta of stroke prone spontaneously hypertensive rats. AB - The effect of fish oil on potassium efflux and basal tension in aortas from stroke prone spontaneously hypertensive rats (SHRSP) was evaluated. Four-week-old male Wistar-Kyoto rats (WKY) and SHRSP were divided into two groups: one received a 5% corn oil diet; the other a 5% menhaden oil diet. After 15 weeks, mean systolic blood pressure (mm Hg) was reduced in SHRSP-fish (202 +/- 5) compared to SHRSP-corn (227 +/- 4). Systolic pressure of WKY-fish (146 +/- 3) was not different from WKY-corn (151 +/- 4). Potassium efflux was evaluated with the isotope 86Rb. Basal 86Rb efflux from aorta of SHRSP-corn was evaluated compared to WKY-corn. Diltiazem or sodium nitroprusside decreased 86Rb efflux and basal tension in SHRSP. Basal 86Rb efflux, tension, and the magnitude of this diltiazem or nitroprusside-induced inhibition were decreased in SHRSP-fish. At maximal diltiazem or nitroprusside concentration, 86Rb efflux from both SHRSP dietary groups was similar but still greater than control aorta. The IC50 values for diltiazem or nitroprusside effects on 86Rb efflux and tension were not altered by diet in SHRSP. Qualitatively similar changes in basal 86Rb efflux and tension were noted in WKY-fish compared to WKY-corn. These experiments demonstrate that dietary fish oil supplementation decreased calcium-sensitive 86Rb efflux and basal tension in vascular smooth muscle and suggest that these changes may contribute to the concomitant antihypertensive effect of dietary fish oil in SHRSP. PMID- 1637521 TI - Effects of enalapril on heart failure in hypertensive patients with diastolic dysfunction. AB - Ten hypertensive patients with symptoms of heart failure and normal systolic function but with diastolic dysfunction were treated with 10 mg enalapril twice a day for 9 +/- 3 months to evaluate the effects of this agent alone on heart failure induced by diastolic dysfunction. After therapy, all patients improved and echocardiographic parameters of diastolic dysfunction became normalized. It is concluded that enalapril appears to be useful in the treatment of heart failure in hypertensive patients with normal systolic function and diastolic dysfunction. PMID- 1637522 TI - Comments on "Renal resistive index after captopril test by echo-Doppler in essential hypertension" by Veglio et al. PMID- 1637523 TI - Continuous monitoring of analyte concentrations. AB - We have investigated the application of a modified, heterogeneous, competitive enzyme immunoassay for the continuous measurement of small analytes in a medium stream. The analytical system contains two antibodies that are immobilized on spatially separated areas, one binding the analyte (Ab1) and the other binding the enzyme (Ab2). An analyte-enzyme conjugate serves as signal generator. The analyte-enzyme conjugate functions as a heterobifunctional shuttle that can bind to either antibody. A semipermeable membrane retains the enzyme shuttle in the internal volume of the sensor but permits the passage of small analytes from the medium stream. The amount of enzyme bound to Ab1 is inversely proportional and the amount of enzyme bound to Ab2 is directly proportional to the analyte concentration. We have demonstrated that this analytical system (1) can provide a larger total signal; (2) has a sensitivity comparable with conventional competitive immunoassays; (3) does not require the separation of bound from free antigens; and (4) is therefore suitable for the continuous measurement of analytes in a medium stream. With a model system, an increase from 0 ng ml-1 to 20 ng ml-1 of the steroid hormone progesterone and the subsequent fall to 0 ng ml 1 could be monitored. PMID- 1637525 TI - On-line determination of glucose and lactate concentrations in animal cell culture based on fibre optic detection of oxygen in flow-injection analysis. AB - A flow-injection analysis (FIA) system based on fibre optic detection of oxygen consumption using immobilized glucose oxidase (GOD) and lactate oxidase (LOD) is described for the on-line monitoring of glucose and lactate concentrations in animal cell cultures. The consumption of oxygen was determined via dynamic quenching by molecular oxygen of the fluorescence of an indicator. GOD and LOD were immobilized on controlled pore glass (CPG) in enzyme reactors which were directly linked to a specially designed fibre optic flow-through cell covering the oxygen optrode. The system is linear for 0-30 mM glucose, with an r.s.d. of 5% at 30 mM (five measurements) and for 0-30 mM lactate, with an r.s.d. of 5% at 30 mM (five measurements). The enzyme reactors used were stable for more than 4 weeks in continuous operation, and it was possible to analyse up to 20 samples per hour. The system has been successfully applied to the on-line monitoring of glucose and lactate concentrations of an animal cell culture designed for the production of recombinant human antithrombine III (AT-III). Results of the on line measurement obtained by the FIA system were compared with the off-line results obtained by a glucose and lactate analyser from Yellow Springs Instrument Company (YSI). PMID- 1637524 TI - Laccase-based biosensor for determination of polyphenols: determination of catechols in tea. AB - A new method of amperometric determination of phenolic compounds using an enzyme electrode is proposed. The latter represents the combination of the oxygen electrode and immobilized laccase. Analytical systems of flow injection and batch types were considered. A method of immobilization was developed that provided an increase in the stability of the enzyme. Optimal conditions for biosensor operation were found. The time needed for analysis in the flow injection mode was below 100 s. A column with immobilized enzyme could be used for up to 500 determinations of phenolic compounds without decrease of the enzyme activity. The practical validity of the method was demonstrated by tannin analysis in tea of different brands. PMID- 1637526 TI - A single mode fibre-optic evanescent wave biosensor. AB - This paper reports experimental developments in the construction and operation of a single-mode fibre-optic evanescent wave biosensor using an exposed core silica single-mode fibre embedded in a silica block. The device was able to monitor the concentration of a blue dye, Procion Blue MX-G, in overlayers of various refractive indices. The practicality of such a biosensor has been demonstrated with a colorimetric enzyme assay system. Penicillin G in the 0-0.4 mM concentration range was monitored at 633 nm by the decoloration of the starch iodine reagent when Bacillus cereus penicillinase was immobilized over the exposed core of the monomode fibre. PMID- 1637527 TI - A new membrane electrode for the detection of antibody. AB - A new membrane electrode sensitive to specific antibody is described which incorporates dinitrophenyl antigen in polyvinyl chloride matrix membrane on to the surface of a solid-state graphite-loaded epoxy-resin electrode. The sensitivity of the electrode is based on the ionophoric property of the dinitrophenyl antigen. Response curves for the potassium ion and its specific antibody are reported. PMID- 1637528 TI - Effects of temperature and analyte application technique on neuron-based chemical sensing. AB - Results are presented which enhance the field of neuron-based sensing by providing insight on the effects of operating temperature and analyte application technique (pulse versus back-mixed) on sensing properties. In these studies, serotonin sensing attributes of giant visceral neurons VV1 and VV2 from the pond snail Lymnea stagnalis were measured. Experiments using a rapid fluid-exchange system reveal a concentration-dependent increase in maximum firing frequency similar to that reported earlier for a slow well-mixed application. With a rapid application, however, the maximum firing frequency is reached more quickly, and there is less cell-to-cell variability in both the maximum response and sensitivity. Given an application technique, an increase in temperature causes an increase in sensitivity and maximum firing frequency, as well as a decrease in the time required for the response to return to baseline following removal of the analyte. To provide insights on the kinetics of the serotonin-induced response, the effects of temperature and concentration on the rates of activation, recovery and desensitization were examined in detail. In general, it was found that an increase in temperature increases the rates of activation and desensitization, while the effects on recovery were not apparent. In addition, both the rates of activation and desensitization have a direct dependence on concentration while the rate of recovery has an inverse dependence. PMID- 1637529 TI - Silent violence. PMID- 1637530 TI - Time to take back our streets--and our homes. PMID- 1637531 TI - A public health solution to violent crime. PMID- 1637532 TI - A journalist's eye view of the trauma physician's dilemma. PMID- 1637533 TI - A commentary on violence. PMID- 1637534 TI - Violence and the ear and temporal bone. PMID- 1637535 TI - Physical abuse of children. A retrospective review and an otolaryngology perspective. AB - Child abuse is a common problem seen by practicing physicians. To further define the incidence and the type of head and neck injury in children referred for evaluation of child abuse, a 5-year retrospective study of 4340 patients was undertaken. Of these patients, 2950 (68%) were victims of sexual abuse, while 1390 (32%) were victims of physical abuse. Forty-nine percent of patients abused physically had evidence of injury to the head and neck region, while only 1% of the sexually abused children had injuries in the head and neck area. The age of the patients ranged from 1 day to 17 years, with a mean of 5.6 years. More than 150 of these children were under the age of 1 year; 180 patients were admitted. The average age of the admitted patients was 2.1 years. The alleged perpetrator, mechanism of injury, and location of injury were tabulated. There were 11 deaths in the series (1.6%). Child abuse has been defined in our institution as any injury inflicted on a child. Identification and reporting of suspected child abuse is required by law and essential for the well-being of the abused child. Recommendations are made concerning the evaluation of these children, their management, and the physician's legal responsibility to report suspected cases of child abuse. PMID- 1637536 TI - Gunshot wounds to the head and neck. AB - Gunshot wounds to the head and neck contribute to substantial medical, economic, and social problems in the United States today. The treatment of these patients requires the contemporary head and neck surgeon to be precisely informed in anatomy, wound ballistics, resuscitation, and surgical decision making. Ninety recent cases at the University of Texas Health Science Center affiliated hospitals in Houston were reviewed and are reported. Data show substantial trends in patient demographics and corroborate other reports in the trauma literature. Controversies in patient management continue, but current evidence favors a protocol of selective surgical exploration. PMID- 1637537 TI - The acute management of external laryngeal trauma. A 27-year experience. AB - The acute care of 139 consecutive patients with external laryngeal trauma over a 27-year period is reported. This article represents an effort to periodically reevaluate our care of this relatively infrequent injury and to share our changes and refinements in treatment. This series provides the means to test and establish basic principles in the acute care of external laryngeal trauma because (1) the number of years encompassed by the article, (2) most patients were managed by one physician, (3) the relative consistency of management principles throughout the series, and (4) the delivery of trauma care in Dallas County, Texas, reflects a broad sampling of this injury within the geographic area. PMID- 1637538 TI - Management of combined frontonaso-orbital/skull base fractures and telecanthus in 355 cases. AB - In regard to the multiple problems of reconstruction concerning this fracture pattern, we developed various methods to achieve optimal results. As various vital regions, apart from the nasoethmoidal fractures and aesthetics, are involved, the proposed classification has direct implication for the surgical procedure. Even in intracranial fragment dislocations, cerebral contusion, and elevated intracranial pressure, the subcranial approach, in contrast with the transfrontal access, enables early definitive management of the skull base and the external facial frame in a one-stage procedure. Another method, the symmetrical centripetal compression of the canthal ligaments and naso-orbital bone fragments, enables correct reduction of the telecanthus. The significant reduction of morbidity and complication rate to a minimum confirms the efficiency of our treatment modalities. PMID- 1637539 TI - Complications of endoscopic sinus surgery. AB - Endoscopic sinus surgery has become popular during recent years. We report the complications of endoscopic sinus surgery in 593 patients in whom 1235 sides were operated on. Forty-five patients had complications, in three of whom they were systemic. The remaining 42 patients had complications on 52 (4.2%) sides; these complications were mostly minor. In 0.3% of the sides operated on, potentially serious complications, such as orbital hematoma or cerebrospinal fluid leak, were seen. None of these patients developed loss of vision or meningitis. Absence of the middle turbinate is a risk factor for developing complications. We conclude that endoscopic sinus surgery is a safe procedure in experienced hands. PMID- 1637540 TI - Otolaryngologic manifestations of child abuse. AB - Currently, awareness is growing of child abuse in the medical and lay communities. To familiarize otolaryngologists with the head and neck findings in abused children, we retrospectively analyzed 85 patients admitted to an inner city hospital with the diagnosis of abuse or neglect. Forty-eight children (56%) had abnormalities within the head and neck region. Excluding coincidental findings, 31 children (36%) had findings that could be directly linked to physical abuse or neglect. The face was the region with the most abnormal findings in our study (25 children [30%]). Soft-tissue findings were the most numerous (27 children [32%]). The literature is reviewed on the subject of otolaryngologic manifestations of abuse. PMID- 1637541 TI - Auricular injury as a presentation of child abuse. AB - Child abuse causes serious physical and emotional injury. Those abused, however, are usually unable or unwilling to gain access to agencies that might help them. The otolaryngologist, while usually not the patient's primary physician, may be in the position to detect child abuse. We describe a 3-year-old boy who sustained auricular trauma as the result of child abuse. The importance of physician recognition of an abuse case and the institution of appropriate measures are discussed. PMID- 1637542 TI - Endotracheal tube safety during electrodissection tonsillectomy. AB - A case report of an endotracheal tube fire occurring during electrodissection tonsillectomy is presented. The authors believe that this incident occurred because a retrograde leak of ventilating gases around an uncuffed endotracheal tube during positive-pressure ventilation produced a high oxygen concentration in the mouth, allowing indirect ignition of the tube. In vitro testing supported this hypothesis. Ignition tests on polyvinylchloride endotracheal tubes using electrocautery in various oxygen concentrations were performed. As oxygen concentration increased, the endotracheal tube could be moved further from the cautery and still allow ignition of the tube. At 52% oxygen, with the cautery set at 25-W coagulation current, the endotracheal tube could not be ignited. Recommendations to prevent a recurrence of this incident are included. PMID- 1637543 TI - Conservative endoscopic surgery in inverted papilloma. Preliminary report. AB - Inverted papilloma is noted for recurrence and occasional association with malignancy, leading most authors to recommend lateral rhinotomy as the initial surgical approach in all cases; however, conservative surgery has been reported to be effective in selective cases. Endoscopic control was used in the surgical treatment of three cases of inverted papilloma. In all three cases, the lesions were unilateral and localized, with limited extension into the sinonasal region, and they were not associated with malignancy or recurrent (as proved by endoscopy, computed tomography, and histopathologic examination). Total removal of the mass was achieved through a conservative intranasal approach. Endoscopic follow-up for periods ranging between 12 and 39 months, with an average of 23 months, failed to identify any recurrence. These findings point to the feasibility of applying this conservative endoscopic approach for total excision of limited lesions of inverted papilloma. PMID- 1637544 TI - Acquired flaccid larynx. A case report supporting the neurologic theory of laryngomalacia. AB - Congenital flaccid larynx, also known as laryngomalacia, is a common clinical entity accounting for approximately 60% of laryngeal problems in the newborn. It is a benign and relatively asymptomatic condition that patients often outgrow by 12 to 18 months of age. A variety of mechanisms have been proposed to explain laryngomalacia including cartilage immaturity and poor neuromuscular control secondary to hypomaturity or dysfunction. This entity has only recently been described as an acquired disorder. A case of an 11-year-old boy who presented with basilar artery thrombosis and a midpontine infarction is described. Inability to extubate despite spontaneous respirations prompted flexible laryngoscopy, which revealed complete supraglottic collapse with airway obstruction. The patient was successfully treated with an epiglottoplasty. This case supports the neuromuscular dysfunction theory as a cause of laryngomalacia. PMID- 1637545 TI - Stomal seeding by percutaneous endoscopic gastrostomy in patients with head and neck cancer. AB - Presented is the first known case of squamous cell carcinoma that developed at the site of a "pull" type percutaneous endoscopic gastrostomy stoma. The patient had advanced squamous cell carcinoma of the pharynx when the percutaneous endoscopic gastrostomy tube was placed. This article should serve as a warning of this potential complication. Alternate techniques and other precautionary methods are described. PMID- 1637547 TI - A foresight: the burned oil wells in Kuwait. PMID- 1637546 TI - Kyoshiro Yamakawa, MD, and temporal bone histopathology of Meniere's patient reported in 1938. Commemoration of the centennial of his birth. PMID- 1637548 TI - Controlled exposures of volunteers to respirable carbon and sulfuric acid aerosols. AB - Respirable carbon or fly ash particles are suspected to increase the respiratory toxicity of coexisting acidic air pollutants, by concentrating acid on their surfaces and so delivering it efficiently to the lower respiratory tract. To investigate this issue, we exposed 15 healthy and 15 asthmatic volunteers in a controlled-environment chamber (21 degrees C, 50 percent relative humidity) to four test atmospheres: (i) clean air; (ii) 0.5-microns H2SO4 aerosol at approximately 100 micrograms/m3, generated from water solution; (iii) 0.5-microns carbon aerosol at approximately 250 micrograms/m3, generated from highly pure carbon black with specific surface area comparable to ambient pollution particles; and (iv) carbon as in (iii) plus approximately 100 micrograms/m3 of ultrafine H2SO4 aerosol generated from fuming sulfuric acid. Electron microscopy showed that nearly all acid in (iv) became attached to carbon particle surfaces, and that most particles remained in the sub-micron size range. Exposures were performed double-blind, 1 week apart. They lasted 1 hr each, with alternate 10 min periods of heavy exercise (ventilation approximately 50 L/min) and rest. Subjects gargled citrus juice before exposure to suppress airway ammonia. Lung function and symptoms were measured pre-exposure, after initial exercise, and at end-exposure. Bronchial reactivity to methacholine was measured after exposure. Statistical analyses tested for effects of H2SO4 or carbon, separate or interactive, on health measures. Group data showed no more than small equivocal effects of any exposure on any health measure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637549 TI - Negative regulation of gene expression by TGF-beta. AB - Stromelysin gene expression is transcriptionally activated by a number of growth factors (e.g., EGF and PDGF), tumor promoters (e.g., TPA), and oncogenes (e.g., ras, src) through an AP-1-dependent mechanism. TGF-beta repression of stromelysin induction is mediated at the level of transcription by an element located at position -709 in the rat stromelysin promoter referred to as the TGF-beta inhibitory element (TIE). A TIE-binding protein complex is induced by treatment of rat fibroblasts with TGF-beta. This protein complex contains the protooncogene c-fos, and induction of c-fos by TGF-beta is required for the repressive effects of TGF-beta on stromelysin gene expression. Interestingly, c-fos induction is also required for stimulation of stromelysin expression by EGF in rat fibroblasts. Preliminary studies suggest that differential regulation of members of the jun family of early-response genes may explain this apparent paradox and determine whether stromelysin is induced or repressed by growth factors. TGF-beta stimulation therefore initiates a cascade of events that results in a specific pattern of gene expression: the direct stimulation of early-response genes can lead to subsequent induction or repression of other genes. Growth factor regulation of matrix metalloproteinases appears to play a role in embryonic development in the morphogenesis of the murine lung. Treatment of embryonic lungs in organ culture with the growth factors EGF or TGF-alpha results in stimulation of growth and inhibition of branching morphogenesis. A similar inhibition of branching was observed when these lung rudiments were treated with the matrix metalloproteinase collagenase. Most interestingly, the effects of EGF and TGF alpha can be completely reversed by the tissue inhibitor of metalloproteinases, TIMP. TGF-beta has the opposite effect on growth of murine lung rudiments--growth is inhibited in a dose-dependent manner. This example illustrates a potential role for growth factor regulation of matrix-degrading metalloproteinases in complex developmental processes. PMID- 1637550 TI - Modulation of vascular cell behavior by transforming growth factors beta. AB - The vascular cell responses to the type 1, 2, and 3 isoforms of transforming growth factor-beta (TGF-beta 1, TGF-beta 2, TGF-beta 3) were studied using bovine aortic endothelial (BAECs) and smooth muscle cells (BASMC3) as well as rat epididymal fat pad microvascular endothelia (RFCs). Three distinct bioassays indicated that TGF-beta elicits results that do not differ significantly from those of the TGF-beta 1 isoform in all three cell populations. These assays are: inhibition of proliferation, cell migration, and neovascularization. By contrast the cellular responses to TGF-beta 1 and TGF-beta 3 differed from those to TGF beta 2. Three distinct receptor assays revealed the presence of type I and type II TGF-beta 1 cell surface binding proteins on BAECs, BASMCs, and RFCs. Experimentation to decipher cell surface binding by the different isoforms revealed that iodinated TGF-beta 1 bound to the surface of all three vascular cell types can be competed off in similar fashion by either TGF-beta 1 or TGF beta 3; however, competition with TGF-beta 2 produced unique binding profiles dependent on the cell type examined. The ratios of type I to type II TGF-beta receptors in these three vascular cell types vary from 1:1 in BAECs to 1.5:1 in RFCs to 3:1 in BASMCs and can be correlated with the differences noted in cellular responses to TGF-beta 1 and TGF-beta 2 in proliferation, migration, and in vitro angiogenic assays.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637551 TI - The role of TGF-beta s in mammalian development and neoplasia. AB - To date, three mammalian TGF-beta isoforms have been identified, each encoded by different genetic loci. Through each is very similar in primary amino acid structure, there are clear differences both in the mature bioactive peptide region and in the latency-associated peptide, which could potentially confer differential biological specificity. As one route to investigate differential biological function in vivo we have used gene specific probes for in situ hybridization studies to examine the distribution of RNA transcripts during mammalian embryogenesis. Mouse embryos from 6 to 14.5 gestational age and human embryos from 32 to 57 days post-fertilization have been probed. A general conclusion from these studies is that each TGF-beta gene has a distinct, through overlapping, pattern of transcript distribution and that this pattern, in most cases, is conserved between mouse and man. We have focused on the biological function the TGF-betas play in certain epithelia and in cardiogenesis, which will be discussed in this presentation. PMID- 1637552 TI - Regulation of mammary growth and function by TGF-beta. AB - We have previously shown that TGF-beta 1 rapidly and reversibly inhibits ductal growth in vivo when administered by miniature slow-release plastic implants. A possible role for endogenous TGF-beta 1 was suggested by the observation that the normal gland displayed substantial, developmentally regulated levels of TGF-beta 1 transcripts and protein. These studies have now been extended to include the other two mammalian TGF-beta isoforms. When tested with slow-release plastic implants, TGF-beta 2 and TGF-beta 3 also caused disappearance of the proliferating mammary stem cell layer, with rapid involution of ductal end buds and cessation of glandular growth. None of the isoforms was active in inhibiting alveolar morphogenesis. We conclude that under the conditions of these tests, the three mammalian isoforms are functionally equivalent. However, striking differences in patterns of gene expression and in the distribution of immunoreactive peptides suggest that TGF-beta 2 was expressed only at low levels, and mainly during pregnancy. TGF-beta 3 was expressed in ductal stroma and epithelium, and was the only isoform detected in myoepithelial cells. Developing alveolar tissue and its associated ducts displayed striking TGF-beta 3 gene expression and immunostaining, which were greatly reduced during lactation. We are now investigating the possibility that the observed high levels of TGF-beta expression in pregnancy, particularly of TGF-beta 3, and the absence of substantial expression of any isoform during lactation, may indicate a role for the TGF-beta in regulating functional differentiation or the onset of milk secretion. PMID- 1637553 TI - TGF-beta 3-mediated tissue interaction during embryonic heart development. AB - A critical process during early heart development is the formation of mesenchymal cells which will contribute to valves and septa of the mature heart. These cells arise by an epithelial-mesenchymal transformation of endothelial cells in the atrioventricular (AV) canal and outflow tract areas of the heart. Adjacent endothelial cells in the atrium and ventricle remain epithelial. A three dimensional collagen gel culture system has been exploited to examine the interactions that mediate this transformation. The AV canal myocardium produces a stimulus that is transmitted through an intervening extracellular matrix to the AV canal endothelium. This interaction is regionally specific, such that ventricular myocardium does not provide an adequate stimulus and ventricular endothelium does not respond to the AV canal myocardial stimulus. Exogenous TGF beta 1 (or TGF-beta 2) can complement ventricular myocardium to produce transformation by AV canal endothelium. A blocking antibody, effective against several TGF-beta, prevents cell transformation. To identify the specific member of the TGF-beta family that functions in situ, antisense oligonucleotides for each of the numbered TGF-beta were topically added to AV canal explant cultures. Only the oligonucleotide targeted to TGF-beta 3 was an effective inhibitor of mesenchymal cell formation. Studies have been undertaken to localize specific mRNas by in situ hybridization and RNase protection assays. These assays have concentrated on the regional and temporal appearance of TGF-beta 2 and 3. Surprisingly, RNase protection assays with a TGF-beta 3 sense probe showed the presence of a transcript complementary to TGF-beta 3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637554 TI - The bone morphogenetic protein family and osteogenesis. AB - The BMPs (bone morphogenetic proteins) are a group of related proteins originally identified by their presence in bone-inductive extracts of demineralized bone. By molecular cloning, at least six related members of this family have been identified and are called BMP-2 through BMP-7. These molecules are part of the TGF-beta superfamily, based on primary amino acid sequence homology, including the absolute conservation of seven cysteine residues between the TGF-betas and the BMPs. The BMPs can be divided into subgroups with BMP-2 and BMP-4 being 92% identical, and BMP-5, BMP-6, and BMP-7 being an average of about 90% identical. To examine the individual activities of these molecules, we are producing each BMP in a mammalian expression system. In this system, each BMP is synthesized as a precursor peptide, which is glycosylated, processed to the mature peptide, and secreted as a homodimer. These reagents have been used to demonstrate that single molecules, such as BMP-2, are capable of inducing the formation of new cartilage and bone when implanted ectopically in a rodent assay system. Whether each of the BMPs possesses the same inductive activities in an animal is the subject of ongoing research. Based on the chondrogenic and osteogenic abilities of the BMPs in the adult animal, the expression of the mRNAs for the BMPs has been examined in the development of the embryonic skeleton by in situ hybridization. These studies demonstrate that the BMP mRNAs are spatially and temporally expressed appropriately for the proteins involved in the induction and development of cartilage and bone in the embryonic limb bud.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637555 TI - Mullerian inhibiting substance in reproduction and cancer. AB - During embryogenesis normal male phenotypic development requires the action of Mullerian Inhibiting Substance (MIS) which is secreted by Sertoli cells of the fetal testis. As testes differentiate in genetic (XY) males, they produce MIS which causes regression of the Mullerian ducts, the anlagen of the female reproductive tract. Soon thereafter, testicular androgens stimulate the Wolffian ducts. In females, on the other hand, MIS is not produced by grandulosa cells until after birth, before which, estrogens induce Mullerian duct development, while the Wolffian ducts passively atrophy in the absence of androgenic stimulation. High serum MIS levels in males are maintained until puberty, whereupon they fall to baseline levels. In females MIS is undetectable in serum until the peripubertal period when values approach the baseline levels of males. This distinct pattern of sexual and ontogenic expression presupposes and requires tight regulation. MIS may play a role in gonadal function and development. Our laboratory has shown that an important role for ovarian MIS is to inhibit oocyte meiosis, perhaps providing maximal oocyte maturation prior to selection for ovulation and subsequent fertilization. Furthermore, Vigier et al. (Development 100:43-55) have recently obtained evidence that MIS may influence testicular differentiation, coincident with inhibition of aromatase activity. Current structure-function studies demonstrate that MIS, like other growth regulators in its protein family, requires proteolytic cleavage to exhibit full biological activity. MIS can be inhibited by epidermal growth factor. This antagonism, which is common to all MIS functions so far investigated, is associated with inhibition of EGF receptor autophosphorylation. We have provided evidence that bovine MIS can inhibit female reproductive tract tumors arising in adults.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637556 TI - TGF-beta regulation of epithelial cell proliferation. AB - The predominant effect of TGF-beta 1 on cell proliferation is inhibition. Earlier studies demonstrated that TGF-beta 1 inhibition of skin keratinocyte proliferation involves suppression of c-myc transcription and indirect evidence suggested that the protein product of the retinoblastoma gene (pRB) may be involved in this process. Skin keratinocytes transformed by SV40 and human papilloma virus-16 (HPV-16) or HPV-18 resisted growth inhibition and suppression of c-myc mRNA by TGF-beta. Transient expression of HPV-16 E7 gene, adenovirus E1A, and SV40 large T antigen (TAg) blocked the TGF-beta 1 suppression of c-myc transcription. Studies with transformation-defective mutants of E1A and TAg suggested that a cellular protein(s) that interacts with a conserved domain of the DNA tumor virus oncoproteins mediates TGF-beta 1 suppression of c-myc transcription and keratinocyte growth. Transient expression of pRB in skin keratinocytes repressed human c-myc promoter/CAT transcription as effectively as TGF-beta 1. The same c-myc promoter region, termed the TGF-beta Control Element (TCE), was required for regulation by both TGF-beta 1 and pRB. TCE bound a cellular protein of approximately 106 kDa and this binding was decreased by TGF beta 1 treatment. Our data indicate that pRB can inhibit c-myc transcription and suggest the involvement of cellular factor(s) in addition to pRB in the TGF-beta 1 pathway for the suppression of c-myc transcription and growth inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637557 TI - Differential expression of the TGF-beta isoforms in embryogenesis suggests specific roles in developing and adult tissues. AB - The TGF-beta's are multifunctional, pleiotropic molecules with major effects in control of cellular migration, cellular proliferation, and elaboration of extracellular matrix. Thus far, five distinct isoforms of TGF-beta have been described, each approximately 65-85% homologous and containing the characteristic 9 positionally conserved cysteine residues. Although the actions of the activated mature forms of the different isoforms on cells are qualitatively similar in most cases, there are a few examples of distinct activities. For example, TGF-beta's 1 and 3, but not TGF-beta 2, inhibit the growth of large vessel endothelial cells, and TGF-beta's 2 and 3, but not TGF-beta 1, inhibit the survival of cultured embryonic chick ciliary ganglionic neurons. In addition, selective targeting of the latent forms of the TGF-beta's is suggested by the observation that latent TGF-beta 2 is the prominent isoform found in body fluids such as amniotic fluid, breast milk, and the aqueous and vitreous humor of the eye; it is noteworthy in this regard that TGF-beta 2 is unique among various isoforms in that it lacks a RGD integrin-binding sequence in its precursor. The most dramatic differences in the TGF-beta isoforms are seen at the level of expression, where there is now a wealth of data demonstrating both spatially and temporally distinct expression of both the mRNAs and proteins in developing tissues, regenerating tissues, and in pathologic responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637558 TI - Effect of occlusion on in vitro percutaneous absorption of two compounds with different physicochemical properties. AB - It is a general rule that percutaneous absorption is increased when the site of application is occluded. In this study we compared the in vitro permeation profiles of two molecules with different physicochemical properties under occluded versus unoccluded conditions. Human abdominal skin samples were mounted on Dianorm Teflon macro 1 cells and Franz diffusion cells which represented occluded or unoccluded conditions, respectively. Our data show that occlusion increased the permeation of citropten (lipophilic compound) 1.6 times whereas that of caffeine (amphiphilic compound) remained unchanged. This lack of penetration enhancement under occluded conditions has also been observed by other authors, especially concerning hydrophilic and slightly lipophilic molecules. Our results support the view that occlusion does not necessarily increase the percutaneous absorption of a chemical. PMID- 1637559 TI - Interaction of minoxidil with pigment in cells of the hair follicle: an example of binding without apparent biological effects. AB - To identify minoxidil target cells in hair follicles we followed the uptake of radiolabeled drug in mouse vibrissae follicles both in vitro and in vivo. Autoradiography showed that both 3H-minoxidil and 3H-minoxidil sulfate accumulated in the differentiating epithelial matrix cells superior to the dermal papilla, a distribution similar to that of pigment. Minoxidil localized in melanocytes, melanocyte processes, and areas of greater melanin concentrations within the epithelial cells. Although uptake of minoxidil was significantly less in unpigmented follicles, the drug stimulated proliferation and differentiation of both pigmented and unpigmented follicles. Labeled minoxidil bound to Sepia melanin and was displaced with unlabeled minoxidil and other electron donor drugs. This interaction with melanin acts as a targeting mechanism of minoxidil to pigmented hair follicles but has no apparent functional significance in hair growth. This work illustrates how measurement of drugs in hair may be biased by pigmentation. PMID- 1637560 TI - Assay of erythromycin in tape strips of human stratum corneum and some preliminary results in man. AB - The antibiotic erythromycin is used topically in the treatment of acne vulgaris. In order to evaluate the in vivo cutaneous absorption behavior of erythromycin in man, an analytical procedure for erythromycin in stratum corneum tape strips was developed. Erythromycin was extracted from tape strips using solid-phase extraction, followed by alkaline diethyl ether extraction. Reconstituted extracts were analyzed by RP-HPLC with electrochemical detection. This procedure proved to be adequate in a pilot experiment in man, topical erythromycin appearing to be distributed over the stratum corneum, its upper layers displaying an inward decreasing gradient. PMID- 1637561 TI - The local side effects of transdermally absorbed nicotine. AB - Percutaneous nicotine administration induces predominant sudorific and rubiform responses in the skin which may be accompanied by subtle piloerection, hyperalgesia and pruritus (although these signs are not overtly manifest). These dermal responses are complex and mechanisms have been proposed for the direct nicotine-stimulation of sweat glands, piloerection and vasoconstriction. These reactions are accompanied by secondary activation and release of vasodilator peptides which produce a predominating vasodilator tone following topical administration, this response masking the direct axon reflex-mediated vasoconstriction. PMID- 1637562 TI - Comparative atrophogenicity potential of medium and highly potent topical glucocorticoids in cream and ointment according to ultrasound analysis. AB - 24 healthy volunteers with no history of skin disease were entered in a 6-week double-blind randomized study to compare the atrophogenicity potentials of both cream and ointment forms of triamcinolone acetonide and clobetasol propionate. The atrophogenicity potential of cream preparations turned out to be greater than that of ointment preparations containing identical amounts of the same glucocorticoid. This result proves both the reproducibility of the assay and the general character of the phenomenon in view of the limited previous evidence. PMID- 1637563 TI - Comparison of infrared and helium-neon lasers in the measurement of blood flow in human skin by the laser-Doppler technique. AB - Histamine-induced changes in blood flow in normal human skin were assessed by laser-Doppler velocimetry using 2 lasers of different wavelengths: 780 nm infrared and 633 nm helium-neon. The visible flare response in skin was also measured by planimetry. Laser-Doppler velocimetry was shown to detect both the magnitude of the change in blood flow caused by histamine and also the extent of the changes in the skin. Both parameters were related to the dose of histamine, which ranged between 25 and 750 pmol/site. There was good correlation between the magnitude of the histamine-induced blood flow change and the extent of the response. The flare induced by histamine and measured by planimetry was similar in extent to the blood flow change recorded by laser-Doppler velocimetry. No difference in either the magnitude or the extent of blood flow changes in response to histamine, as measured by laser-Doppler velocimetry, were found when lasers of different wavelengths were used. PMID- 1637564 TI - Effects of calcipotriol (MC 903) and calcitriol after topical application on the skin of hairless rats. Much lower effect of calcipotriol on systemic calcium homeostasis. AB - Topical application of calcitriol or its analogs is a new approach for treating psoriasis, but may be limited by systemic calcitropic effects. Calcipotriol (MC 903) is a novel calcitriol analog with low calcitropic potency after systemic application. To compare the topical potency of calcitriol and calcipotriol we applied the two drugs on the right flanks of hairless rats for 10 days. In concentrations of 0.001-0.01 g/100 ml (ethanol) the two drugs are equally effective in inducing changes in the horny layer of the skin (increase in the amount of horny material that is able to be desquamated). This can be interpreted as a stimulation of terminal keratinocyte differentiation. However, only calcitriol caused a significant rise in the serum calcium concentration. In conclusion, calcitriol and calcipotriol seem to be equally effective after topical application on the skin of hairless rats, but calcipotriol has a much lower systemic calcium liability. PMID- 1637565 TI - Role of transepidermal and transfollicular routes in percutaneous absorption of hydrocortisone and testosterone: in vivo study in the hairless rat. AB - The importance of the transappendageal route on percutaneous absorption was assessed in the hairless rat. Skin permeation of two steroids, hydrocortisone and testosterone, was evaluated in vivo on normal and artificially damaged skin in which follicles and sebaceous glands disappeared during healing. The test compounds were applied for periods of 0.5, 2 and 6 h. Thereafter, the stratum corneum reservoir function, the epidermal and dermal distribution profiles, and systemic absorption were determined for both molecules. The results presented here show that the reservoir function of the stratum corneum of appendage-free (scar) skin is more pronounced than that of normal skin, whereas the concentration appearing in the epidermis and dermis was greater in normal skin. Moreover, sebaceous glands probably contribute to the penetration of hydrocortisone and testosterone. We show that the relative importance of the skin appendages depends on the intrinsic physical properties of the molecules tested, and the time of application. PMID- 1637566 TI - Combined inter-observer and inter-method variation in bone histomorphometry. AB - Manual methods for the measurement of bone biopsies have largely been superseded by semi-automatic computerised techniques. Histomorphometrists often use control data obtained by other observers using different methods, thus combining inter observer and inter-method variation. We have examined the combined effect of inter-method and inter-observer variation on measurements of bone area, osteoid perimeter, and osteoid width in iliac crest biopsies from healthy subjects, one observer using the manual grid system and the other using a semi-automated technique. Inter-observer and inter-method variation were independently determined, and the proportion of each expressed as a percentage of combined error. Our results indicate that the combination of inter-method and inter observer variation causes significant differences in the values obtained for osteoid perimeter, whereas inter-method variation is mainly responsible for differences in osteoid width values; differences in bone area are largely due to inherent sampling variation. These variations indicate that caution is required when comparison is made with control data from other sources, especially if different techniques are employed. PMID- 1637567 TI - Calcium in osteoblast-enriched bone cells. AB - The exchangeability, location, and amount of the total calcium in bone cells were studied in relation to their osteoblastic activity. Cells were isolated from neonatal rat calvariae by sequential collagenase digestion and incubated with 45Ca2+ before or after various treatments. 45Ca2+, 40Ca2+, and DNA were determined on each cell sample. Long-term experiments were performed on cultured cells. The cells closest to the forming bone had the highest alkaline phosphatase activity and the highest Ca2+ content (i.e., 17 mm Ca2+/l cell water, as compared to soft tissue cells, which have 2-3 mm Ca2+/l (Borle 1981). About 50% of this Ca2+ exchanges readily with 45Ca2+ and appears to be located almost entirely in the cell membrane. Thirty-five percent exchanges only slowly with a t1/2 of 27 hours, and is located within the cell, principally in the mitochondria as seen in pyroantimonate fixed cells (Neuman et al. 1985). In spite of its slow exchange ability, this Ca2+ fraction can be mobilized or augmented rapidly when Ca2+ supply is reduced or increased in vitro or in vivo. 1,25(OH)2D3 given in vivo increased this intracellular Ca2+ when the Ca2+ supply was low and released it when the Ca2+ supply was high. About 15% of the Ca2+ in these cells was nonexchangeable. These results suggest that osteoblasts do process more Ca2+ when closer to the mineralization site. Whether this Ca2+ is en route from blood to bone or from bone to blood will require further study. PMID- 1637568 TI - Bone mass status in different degrees of chronic renal failure. AB - Bone mineral density (BMD) was evaluated in 69 patients with chronic renal failure (CRF) and in healthy controls matched for age, sex, and, for women, menopausal status. Both appendicular (predominantly cortical) and axial (predominantly trabecular) bone mass were measured. Appendicular BMD was measured by single photon absorptiometry on the distal forearm and axial BMD was measured by dual photon absorptiometry on the lumbar spine. Patients were divided into three groups on the basis of creatinine clearance: group 1, 58 to 36 ml/min; group 2, 30 to 18 ml/min; group 3, 15 to 9 ml/min. Both appendicular and axial BMD decreased with the worsening of renal failure. Parathyroid hormone levels were inversely correlated with the values of appendicular BMD. BMD values were significantly lower in postmenopausal than in premenopausal women. Months of menopause were inversely correlated with axial BMD values. Appendicular BMD was lower in CRF patients than in controls, and both appendicular and axial BMD were significantly lower in postmenopausal uremic women than in postmenopausal healthy women. PMID- 1637569 TI - Increased bone volume and reduced bone turnover in vitamin D-replete rabbits by the administration of 24R,25-dihydroxyvitamin D3. AB - To study the effect of a large dose of 24R,25(OH)2D3 on bone metabolism, we treated vitamin D-replete rabbits with the agent for eight weeks. Fifteen rabbits 20 weeks of age were divided into three groups of five animals each. Group I received only the vehicle; groups II and III were given the agent at doses of 10 micrograms/kg/d, and 100 micrograms/kg/d, respectively. Through the dosing period, serum calcium, phosphorus, alkaline phosphatase, and creatinine levels were not altered. By the end of the experiment, serum 1,25(OH)2D or serum 25(OH)D levels did not change, nor did the PTH level. Serum 24,25(OH)2D levels for groups I, II, and III were 5.25 +/- 3.40, 76.16 +/- 19.90 (p less than .01), and 199.0 +/- 30.90 (p less than .01) ng/ml, respectively. The bone mineral content (BMC) significantly increased in group III. The percentages of BMC increase in group III over group I were 14.5% on the femur, 34.1% (p less than .01) on the sixth lumbar vertebra, and 23.3% (p less than .05) on the seventh lumbar vertebra. A marked increase of bone mineral densities in the cancellous bone-rich regions was seen in group III. Bone histomorphometry on the seventh lumbar vertebra demonstrated that both the eroded surface and the osteoclast number were reduced and the surfaces indicating bone formation such as the osteoid surface and the tetracycline double labeled surface were also reduced. However, both the osteoid thickness and the mineral apposition rate increased and the mineral formation rate at the tissue level remained approximately equal to that in the control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637570 TI - Relationships between quantitative histological measurements and noninvasive assessments of bone mass. AB - We performed a comprehensive analysis of the relationships between histologic indices in the iliac crest (cancellous bone volume, trabecular structural indices, cortical width, and core width) and bone density in the spine, hip, and wrist in 81 patients with various metabolic bone diseases including osteoporosis, osteomalacia, hyperparathyroidism, and Paget's disease. In the whole group, all of the histologic indices correlated significantly with bone mineral density (BMD) of the spine and the three regions of the hip (r = 0.28-0.73), with the exception of cortical width which correlated with the hip but not the spine (r = 0.21). There was no relationship between the histologic variables and either the distal or proximal radius. When the osteoporotic subgroup was considered separately, the relationships between BMD and both cancellous bone volume and the structural indices (trabecular number, separation, and thickness) were lost. In contrast, cortical width correlated more strongly with both spine and hip BMD. The relationship between core width and the spine was lost but persisted in the hip region. In female osteoporotic patients alone, only cortical width remained significantly correlated with spine or hip BMD. We conclude that the relationships between bone densities in the axial and peripheral regions and histomorphometric variables in iliac crest are not constant. In addition, cancellous bone volume and the trabecular structural indices relate well to noninvasive axial BMD measurements only in a heterogenous group with a large variance in both parameters. In the more homogeneous group with osteoporosis, cortical width appears to be a more powerful predictor of BMD at the important sites of osteoporotic fracture. PMID- 1637571 TI - A method for estimating the uncertainty of future bone mass. AB - The development of statistical models for estimating fracture probability is a promising method for quantitating and optimizing the clinical utility of bone mass measurements. Earlier models have assumed that future bone mass could be predicted exactly and were, therefore, limited to analyses that assume the loss rate is known in advance. Since bone loss rates may vary over time and cannot be predicted accurately, we have developed a new model, based on empirical data, that estimates the degree of uncertainty associated with predicted bone mass. Without a bone mass measurement, the population mean must be assumed for an individual. For the calcaneus, the standard deviation of the population distribution is about 60 mg/cm2. By measuring bone mass, one can determine how close or far from the mean an individual's true bone mass is, with a standard deviation (SD) of about 3 mg/cm2. Without a subsequent bone mass measurement, our model predicts that the uncertainty (standard deviation) in calcaneal bone mass will increase approximately sixfold (relative to the reproducibility at the initial measurement) over a period of five years for women under age 60, from 3 mg/cm2 to 19 mg/cm2. The five-year increase in uncertainty is approximately fourfold for women over age 60, from 3 to 13 mg/cm2. However, the uncertainty in bone mass for an individual five years after the initial measurement is still only one third to one fifth that of the entire population, and can be reduced to the initial level by obtaining another measurement. Furthermore, the predicted (or measured) values are usually much better estimates of an individual's true bone mass than simply assuming the population average.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637572 TI - Effects of bisphosphonates and inorganic pyrophosphate on osteogenesis in vitro. AB - The bisphosphonates, which are chemically related to pyrophosphate, have been studied extensively both in vivo and in vitro to elucidate their effects on bone tissues and cells. However, because these agents have important effects on bone resorption, the majority of investigations have focused on this area. Few studies regarding direct bisphosphonate effects on bone formation have been carried out in the past and, thus, we chose to use the chick periosteal osteogenesis (CPO) in vitro model system to test the direct effects of pyrophosphate and the bisphosphonates ethane-1-hydroxy-1,1-diphosphate (HEBP) and disodium-1-hydroxy-1 amino-propylidine (APD) on various parameters of osteogenesis in vitro. The data show that the bisphosphonate HEBP inhibits bone mineralization reversibly while APD, at low doses, may actually enhance mineralization of bone. Similarly, pyrophosphate (PPi) will prevent mineralization in CPO cultures. However, CPO cultures can circumvent PPi-mediated blockage of mineralization with longer-term, continuous (10-day) incubation, whereas this does not occur if cultures are incubated continuously with bisphosphonates. Both drugs appear to be able to reverse beta-glycerophosphate-induced changes in alkaline phosphatase activity, but do not appear on their own to regulate the activity of this enzyme. The findings show that in addition to their well-known effects on resorption, bisphosphonates have significant and direct effects on mineralization in bone forming cultures. Their direct effects on osteoblastic activity and differentiation remain to be determined. PMID- 1637573 TI - Immunological screening of SPARC/Osteonectin in nonmineralized tissues. AB - SPARC/Osteonectin is a major bone-related protein that is also present in nonmineralized tissues and in platelets. As compared to bone SPARC/Osteonectin, SPARC/Osteonectin from platelets presents a slightly lower electrophoretic mobility in SDS-PAGE and a 100-fold decreased affinity for a unique monoclonal antibody, Mab2 (Malaval et al. 1991). To check the tissular diversity of SPARC/Osteonectin, protein extracts from bovine bone, nonmineralized tissues, and platelets were screened by immunoblotting and immunoradiometric assay, with Mab2 and three other monoclonal antibodies recognizing distinct epitopes. The SPARC/Osteonectin secreted by a human osteosarcoma cell line (MG63) was also tested. In all the nonmineralized tissues tested (gut, bone marrow, tendon, mesentery, artera, lens, skin, liver, and cornea), SPARC/Osteonectin presents the same immunoreactivity and electrophoretic mobility as in bone. The heavier molecular weight and Mab2-negative form present in platelets seems to be unique to this cell type. Osteosarcoma cell extracts and conditioned media give the same results as bone extracts, indicating that the low molecular weight and Mab2 positive form of SPARC/Osteonectin present in most tissues does not result from proteolytic cleavage in the matrix, but is secreted as such. Bone and platelet SPARC/Osteonectin present different patterns of sensitivity to glycosidases, suggestive of a difference in N-glycosylation. However, these treatments do not affect the decreased affinity of Mab2 for platelet SPARC/Osteonectin, which is not likely to be related to difference in N-glycosylation. PMID- 1637574 TI - Comparison of low-dose intramuscular and intravenous salcatonin in the treatment of primary hyperparathyroidism. AB - The treatment of hypercalcaemia with low-dose salcatonin (100 U/d), administered either as a single intramuscular bolus or as a continuous intravenous infusion for five days, was examined in two groups of 10 patients with primary hyperparathyroidism, in a randomized open parallel study. Both the peak (0.31 +/- 0.035 mmol/L v 0.13 +/- 0.034 mmol/L) and overall (0.073 +/- 0.016 mmol/L v 0.018 +/- 0.016 mmol/L) hypocalcaemic responses were greater in the infusion group. The peak reduction in serum calcium occurred on day 2 of treatment after which there was a progressive attenuation of response. All the differences between the two methods of administration wer due to renal rather than bony effects of salcatonin. Possible causes of progressive resistance to treatment included reductions in sodium excretion and serum phosphate. It is concluded that low-dose salcatonin administered as a continuous infusion was more effective than the same dose given as a bolus. The kidney played a pivotal role both in the cause of the hypercalcaemia and in the response to treatment, including the rapid development of resistance which limits the use of salmon calcitonin in primary hyperparathyroidism to short-term reduction of serum calcium. PMID- 1637575 TI - [Salary in order to fight?. Interview by Kjell Arne Bakke]. PMID- 1637576 TI - [Cosmetic changes of important principles?]. PMID- 1637578 TI - [Safety can mean imprisonment]. PMID- 1637577 TI - [Home care nursing: a bottomless pit]. PMID- 1637579 TI - [Hamar hospital gives responsibility to nurses. Interview by Siv Barstad]. PMID- 1637580 TI - [4-year university education in Iceland: power and prestige but the same salary]. PMID- 1637581 TI - [4-year university education in Iceland: the salary problem is distracting]. PMID- 1637582 TI - [A society president says thanks for the hospitality. Interview by Bjorn Arild Ostby]. PMID- 1637583 TI - [Gene technology--problem-creating progress]. PMID- 1637584 TI - [A bank for good ideas]. PMID- 1637586 TI - [Montebello Center: "soft light and gentle warmth"]. PMID- 1637585 TI - [Tough treatment--successful results. Interview by Liv Sandvand Hergum]. PMID- 1637587 TI - [Health care nurse based on the Oppland model]. PMID- 1637588 TI - [We care for children jointly]. PMID- 1637589 TI - [No thanks to psychiatric nurses]. PMID- 1637590 TI - [Psychiatric health services: granted responsibility, lacking plans]. PMID- 1637591 TI - [Go and lay down, Gunnar]. PMID- 1637592 TI - Pre-emptive analgesia. PMID- 1637593 TI - Transoesophageal pulsed wave Doppler measurement of cardiac output during major vascular surgery: comparison with the thermodilution technique. AB - We measured cardiac output in 12 patients undergoing elective abdominal vascular surgery at specific times during the procedure with simultaneous thermodilution and transoesophageal pulsed Doppler echocardiographic techniques. No patient had clinical evidence of valvular heart disease before surgery. Five patients had echocardiographic evidence of mitral regurgitation on colour-coded Doppler. Using Bland and Altman analysis to compare the cardiac output measurement by the two techniques, the Doppler method overestimated the cardiac output (bias = 0.86 litre min-1) compared with the thermodilution technique and there were wide limits of agreement between the two techniques (+2.4 to -4.1 litre min-1). However, in the seven patients with no evidence of mitral regurgitation, closer agreement (bias 0.14 litre min-1) and narrower limits (+1.6 to -1.3 litre min-1) were observed. We conclude that, in patients with competent mitral valves, transoesophageal echocardiograph may provide accurate determination of cardiac output. PMID- 1637594 TI - Continuous collection of pulse oximetry data: a new, inexpensive, portable computerized method. AB - The availability of reliable pulse oximetry equipment has led to interest in identifying patterns of hypoxaemia in the postoperative period. Methods for the computerized collection and analysis of pulse oximetry data have been described, but these require continuous use of a relatively powerful computer system throughout both the monitoring (data collection) and analysis periods. We have designed a technique which uses a small, portable and relatively inexpensive computer unit for data collection, after which the data may be transferred to a more powerful computer for analysis. Appropriate programming and choice of software have produced a relatively "user friendly" system which can be operated successfully even with minimal computing experience. The unit has the potential to be modified to form the basis of a "medical advice system" which could be used for the "intelligent" monitoring of high risk patients. PMID- 1637595 TI - The United Kingdom as seen by a Japanese anaesthetist. PMID- 1637596 TI - Aspirin, extradural anaesthesia and the MRC Collaborative Low-dose Aspirin Study in Pregnancy (CLASP) PMID- 1637597 TI - Repeated resistance to non-depolarizing neuromuscular blocking drugs in a patient with multiple myeloma. PMID- 1637598 TI - Movements of the vocal cords on induction of anaesthesia with thiopentone or propofol. AB - Using a fibreoptic laryngoscope, we have recorded on video tape the movements of the vocal cords after induction of anaesthesia with either propofol or thiopentone. The angle formed by the vocal cords decreased after induction of anaesthesia in both groups. This reduction in angle was significantly greater in the thiopentone group. The vocal cords closed completely in four patients in the thiopentone group and one patient in the propofol group. This difference may be explained by greater depression of laryngeal reflexes by propofol and this may account for the lower incidence of laryngospasm after induction of anaesthesia with propofol in comparison with thiopentone. PMID- 1637599 TI - Factors affecting magnitude and time course of neuromuscular block produced by suxamethonium. AB - This study was designed to identify factors that significantly alter the magnitude and duration of suxamethonium-induced neuromuscular block in patients with an apparently normal genotype for pseudocholinesterase. One hundred and fifty-six adults (ages 18-65 yr) were allocated to 13 subgroups. Patients in each subgroup received suxamethonium 50-2000 micrograms kg-1. The mechanographic response of the adductor pollicis brevis muscle to ulnar nerve stimulation was recorded. The ED50 was found to be 167 micrograms kg-1, ED90 was 316 micrograms kg-1 and ED95 was 392 micrograms kg-1. The duration of action (delta t) was in agreement with earlier published results. The magnitude of block was dose-related and decreased with increasing onset time (ton) and pseudocholinesterase activity (PChA). Neither age nor gender affected the degree of suxamethonium-induced block. Delta t was dose-related, decreased with increasing PChA, and was shorter for women. Age and ton had no effect on delta t. PMID- 1637600 TI - Haemodynamic effects of isoflurane during propofol anaesthesia. AB - We have studied haemodynamic responses to 0, 0.25, 0.5, 0.75 and 1 MAC isoflurane administration in 10 patients during a zero-order propofol infusion and normocapnia. Isoflurane reduced mean arterial pressure (MAP), systemic vascular resistance and left ventricular stroke work in a dose-dependent manner (29%, 38% and 33%, respectively, at 1 MAC), while cardiac output (CO), stroke volume (SV) and heart rate were not affected significantly. Mean pulmonary artery pressure, pulmonary vascular resistance and right ventricular stroke work decreased by 13%, 10% and 17%, respectively (not significant). Pulmonary capillary wedge pressure and central venous pressure were affected minimally, while intrapulmonary shunting and PaO2 remained constant. It is concluded that administration of isoflurane during infusion of propofol caused a dose-dependent decrease in MAP as a result of afterload reduction without modification in CO or SV. PMID- 1637601 TI - Influence of timing on the effect of continuous extradural analgesia with bupivacaine and morphine after major abdominal surgery. AB - We have studied the effect of continuous extradural analgesia with bupivacaine and morphine, initiated before or after colonic surgery, in a double-blind, randomized study. Thirty-two patients were allocated randomly to receive an identical extradural block initiated 40 min before surgical incision (n = 16) or at closure of the surgical wound (n = 16). The extradural regimen consisted of a bolus of 7 ml of plain bupivacaine 7.5 mg ml-1 plus morphine 2 mg and continuous extradural infusion of a mixture of bupivacaine 7.5 mg ml-1 plus morphine 0.05 mg ml-1, 4 ml h-1 for 2 h, followed by a continuous extradural infusion of a mixture of bupivacaine 2.5 mg ml-1 plus morphine 0.05 mg ml-1, 4 ml h-1, continued for 72 h after operation. In addition, all patients received similar general anaesthesia. There was no significant difference in request for additional morphine and no significant differences between the groups in pain scores (visual analogue scale or verbal) during rest or ambulation at any time of measurement. These results do not suggest that timing of analgesia with a conventional extradural regimen is of major clinical importance in patients undergoing colonic surgery. PMID- 1637602 TI - Somatic movement and oesophageal motility during isoflurane anaesthesia. AB - The quantal responses for somatic movement, and spontaneous and provoked lower oesophageal contractions (motility) were noted at the time of incision in 72 patients aged 40-65 yr, receiving varying concentrations of isoflurane. Probit analysis of the alveolar concentration of isoflurane required to prevent somatic movement revealed an MAC or EC50 (95% confidence limits) of 1.00 (0.82-1.17)% and EC95 of 2.16 (1.69-3.89)%. The EC50 of isoflurane to suppress spontaneous lower oesophageal contractions was 1.27 (1.12-1.43)%, and the EC95 2.13 (1.78-3.22)%. The EC50 for provoked lower oesophageal contractions was 1.31 (0.93-3.48)% and the EC95 was 6.18% (unable to compute confidence limits). PMID- 1637603 TI - Acid-base management during hypothermic cardiopulmonary bypass does not affect cerebral metabolism but does affect blood flow and neurological outcome. AB - In order to compare the effects of blood-gas management on cerebral blood flow, metabolism and neurological outcome after hypothermic cardiopulmonary bypass (CPB) we have studied 65 patients undergoing aorto-coronary bypass surgery allocated randomly to either a pH-stat (temperature-corrected blood-gas management) or an alpha-stat (temperature-uncorrected blood-gas management) group. All patients were examined neurologically on the day before and the 7th day after operation. In 20 patients of the pH-stat group and in 15 patients of the alpha-stat group we measured cerebral blood flow (CBF), using the argon washin technique, and also cerebral oxygen (CMRO2) and glucose (CMRg) uptake. Measurements were performed in awake patients, after induction of anaesthesia with fentanyl, midazolam and pancuronium under normothermic conditions, during CPB at a venous blood temperature of 26 degrees C and at the end of surgery. Compared with postinduction values, hypothermia was associated with an 18% reduction in CBF and decreases in CMRO2 and CMRg of 61% and 60%, respectively, in the alpha-stat group. In the pH-stat group, CMRO2 and CMRg decreased also, by 58% and 74%, respectively, whereas CBF increased by 191%, indicating uncoupling of flow and metabolism. As there were no statistically significant differences between the metabolic variables in both groups, we conclude that acid-base management did not affect cerebral metabolism, despite its influence on blood flow. After rewarming, CBF and cerebral metabolism normalized independently of acid-base management during hypothermia. Nevertheless, neurological dysfunction occurred more often in the pH-stat group (P = 0.036). PMID- 1637604 TI - Does etomidate cause haemolysis? AB - Etomidate is currently presented as a solution with propylene glycol as solvent. This organic solvent has an extremely high osmolality and is probably responsible for some of the side effects of this drug. In order to detect haemolysis, an indication for cell damage, we have measured serum haptoglobin concentrations in 12 healthy male volunteers after administration of etomidate 0.3 mg kg-1. Six subjects received etomidate in propylene glycol (EtoPG) with an osmolality of 4965 mosmol kg-1 and six received etomidate in lipid emulsion (EtoLip, 400 mosmol kg-1). Haptoglobin concentrations in the EtoPG group decreased by 44% and 43% from baseline values at 2 and 4 h after administration, respectively, and were significantly smaller than after administration of EtoLip. After 24 h, haptoglobin concentrations had not reached baseline values. PMID- 1637606 TI - Comparison of the relaxant effects of diazepam, flunitrazepam and midazolam on airway smooth muscle. AB - The mechanisms by which benzodiazepines produce muscle relaxation and respiratory depression are not known, but they may include actions on peripheral benzodiazepine receptors or central GABA receptors, or a direct action on airway smooth muscle may also be involved. We have compared, therefore, the effects of diazepam, flunitrazepam and midazolam on airway tone by measuring isometric tension of guineapig trachealis muscle. Cumulative concentrations of diazepam, flunitrazepam and midazolam caused concentration-dependent relaxation of resting tone in the tracheal smooth muscle with no significant differences in pD2 values (-log EC50--an index of potency) or intrinsic activities (% of maximum response) for relaxations for the three compounds. Pretreatment with propranolol 10(-6) mol litre-1, flumazenil 10(-7) and 10(-6) mol litre-1 or PK11195 10(-6) mol litre-1 had no effect on diazepam- or midazolam-induced relaxation. Diazepam 3 x 10(-6) mol litre-1 pretreatment shifted the concentration-response curves for acetylcholine, histamine and serotonin (5-HT) to the right by a factor of approximately 2. Flunitrazepam 3 x 10(-6) mol litre-1 pretreatment also shifted the curves for histamine and 5-HT similarly to the right, whereas midazolam pretreatment did not inhibit any agonist-induced contractions. These results suggest that benzodiazepines relax airway smooth muscle, not via neural pathways or central and peripheral benzodiazepine receptors, but by a direct action on airway smooth muscle. PMID- 1637605 TI - Flumazenil does not antagonize halothane, thiamylal or propofol anaesthesia in rats. AB - We have studied the effects of flumazenil on sleep time and EEG in rats anaesthetized with 1.5% halothane, propofol 20 mg kg-1, thiamylal 30 mg kg-1, or combinations of diazepam 5 mg kg-1 and anaesthetic agents. We also studied the effects of flumazenil 0.3, 3 and 30 mg kg-1 on behaviour and EEG. Flumazenil 0.3 and 3 mg kg-1 alone had no effect on behaviour or EEG, but flumazenil 30 mg kg-1 had depressive effects similar to those of diazepam on behaviour and EEG. Flumazenil 0.3, 3 and 30 mg kg-1 i.v., antagonized the effects of diazepam 10 mg kg-1 i.v. on behaviour and EEG. Flumazenil had no antagonistic effect on sleep time induced by anaesthetic agents, but flumazenil 30 mg kg-1 potentiated propofol-induced anaesthesia. Flumazenil did not affect anaesthesia-induced EEG changes. Diazepam 5 mg kg-1 potentiated anaesthesia. Flumazenil antagonism of diazepam potentiation varied with anaesthetic agent: flumazenil 0.3 mg kg-1 antagonized diazepam action in halothane anaesthesia, but 30 mg kg-1 was required in propofol anaesthesia; this large dose was insufficient in thiamylal anaesthesia. PMID- 1637607 TI - Comparison of the inhibitory effect of propofol, thiopentone and midazolam on neutrophil polarization in vitro in the presence or absence of human serum albumin. AB - Anaesthetic agents inhibit some aspects of immune function and this may be clinically important when prolonged infusions are used in an intensive care unit. We have studied the effects of propofol, thiopentone and midazolam on neutrophil polarization in vitro. At concentrations seen in plasma during anaesthesia, propofol and thiopentone produced significant (approximately 50%) and comparable degrees of inhibition. Inhibition was complete with greater concentrations of these drugs. When compared with equivalent concentrations of midazolam, propofol produced more inhibition (P less than 0.01) at all concentrations investigated, except the smallest. Midazolam produced no effect at clinically relevant concentrations. The effect of propofol was not attributable to its lipid carrier vehicle, as 10% Intralipid alone augmented neutrophil polarization. Human serum albumin conferred some degree of protection against the inhibition produced by clinically relevant concentrations of propofol and thiopentone, but not that produced by greater concentrations of these drugs. PMID- 1637608 TI - EEG and auditory evoked potential P300 compared with psychometric tests in assessing vigilance after benzodiazepine sedation and antagonism. AB - We have compared the EEG and auditory evoked wave P300 with psychometric tests in assessing vigilance after flumazenil antagonism of midazolam sedation in 12 healthy volunteers. Measurements were made before and after midazolam 0.1 and 0.2 mg kg-1 i.v., and immediately and 30, 60, 120 and 240 min after administration of flumazenil 1 mg. The sedative effects of midazolam and antagonism by flumazenil resulted in alterations in EEG, P300 and psychometric tests (syndrome short test, letter cancellation, choice reaction and recognition). However, 60 and 120 min after flumazenil a decrease in test performance indicating rebound sedation was seen only in P300 mapping. Thus P300 mapping was a sensitive method of detecting subtle differences in vigilance. Rebound sedation occurred even when midazolam 0.2 mg kg-1 was antagonized with an adequate dose of flumazenil. We suggest that it is advisable to supervise patients for at least 240 min after flumazenil antagonism of midazolam 0.2 mg kg-1. PMID- 1637609 TI - Influence of vitamin B12 status on the inactivation of methionine synthase by nitrous oxide. AB - We have studied the influence of maternal serum B12 concentration on the inactivation of placental methionine synthase activity by nitrous oxide in an obstetric population. This group was known to include patients with a wide range of B12 values. Over 70% of patients were given nitrous oxide either for analgesia during labour or for delivery by Caesarean section, for periods ranging from a few minutes to 11 h. Patients undergoing normal delivery and Caesarean section under extradural anaesthesia served as controls. There was a highly significant relation between placental methionine synthase activity and duration of exposure to nitrous oxide. Inactivation was slower than that described for the liver, which may reflect the intermittent use. There was also a significant relation between maternal B12 and placental methionine synthase activity, but there was a wide scatter of results and the data were not thought to be predictive. There was evidence that inactivation by nitrous oxide was more rapid in patients with small concentrations of B12. We conclude that some patients with reduced serum concentrations of B12 may be at a disadvantage with nitrous oxide anaesthesia. PMID- 1637610 TI - In vitro diagnosis of malignant hyperthermia: influence of electrical stimulation on the contracture response to caffeine. AB - We have examined the influence of electrical stimulation on caffeine-induced tension generation during contracture testing used to diagnose malignant hyperthermia. The cumulative contracture response to caffeine was compared in pairs of morphologically comparable muscle bundles obtained from the same patient. Only one of the two bundles was stimulated electrically during the test. Statistically significant differences in tension were found at caffeine concentrations greater than or equal to 4 mmol litre-1, the tension developed being invariably larger in the unstimulated fascicles. These results suggest that electrical stimulation results in suppression of the dose-dependent, caffeine induced contracture. This effect could be a result of the potentiation of twitch tension by caffeine, muscle fatigue, or both. Overall, the observed differences did not alter the in vitro diagnosis of malignant hyperthermia. PMID- 1637611 TI - Prospective, controlled, double-blind study of i.v. tenoxicam for analgesia after thoracotomy. AB - We have shown that a single i.v. dose of tenoxicam 20 mg, after thoracotomy, when compared with placebo in 20 patients (with one exclusion), was associated with a reduction in consumption of papaveretum, assessed by patient-controlled analgesia, of 2.2 mg h-1 (22%) to 4 h and 1.4 mg h-1 (23%) to 12 h after operation (repeated measures analysis of variance: P less than 0.01). There was no reduction from 12 to 24 h. There was no significant difference between groups in pain scores or in side effects. PMID- 1637612 TI - Overdose of opioid from patient-controlled analgesia pumps. AB - Two incidence have occurred in our hospital when a patient-controlled analgesia pump has accidentally delivered the whole contents of the syringe of diamorphine (60 mg) over a period of approximately 1 h. Electrical corruption of the pumps' program has been identified as the probable cause. All pumps of this type have been modified to prevent such occurrences. PMID- 1637613 TI - Tracheal models which simulate the compliance of the adult male trachea. AB - Earlier models of the human trachea have not taken the characteristic compliance of the trachea into account. Two tracheal models are presented, which simulate the compliance of the adult male human trachea, intended for more valid laboratory testing of the function of the cuffs of tracheal tubes. The two models simulate the conditions with and without controlled ventilation. PMID- 1637614 TI - [The surgeon, the surgery and the new techniques]. PMID- 1637615 TI - [Preoperative radiotherapy in locally advanced rectal cancer: risks and complications?]. AB - Adjuvant radiotherapy in advanced rectal cancer is currently considered of interest: preoperative radiotherapy in particular seems to provide better results. However, doubts in its use arise from fear of technical difficulties at surgery and increase of complications. In Authors' opinion, though, preoperative radiotherapy associated with perineal omentoplasty represents a real progress in the management of rectal cancer. Preliminary experience supports this feeling. PMID- 1637616 TI - Modern operative thoracoscopy. AB - Laparoscopic surgery has demonstrated advantages of less pain, early recovery, and cosmesis. Applying laparoscopic surgical techniques to thoracic procedures may allow for similar advantages. New instrumentation provides for greater versatility in treating thoracic conditions. Described herein is the use of thoracoscopy for a variety of thoracic procedures. PMID- 1637617 TI - Thoracoscopic treatment of spontaneous pneumothorax without pleurodesis: a preliminary report. AB - Laparoscopy has shown to be associated with less morbidity than laparotomy. General surgeons are realizing that procedures so far performed through traditional incisions can be equally performed effectively by laparoscopy. Likewise it is apparent that some thoracic procedures are amenable to thoracoscopic approach. With the development of new instrumentation thoracoscopy is effective for the treatment of spontaneous pneumothorax. Pleurodesis seems to increase the morbidity associated with the thoracoscopic procedure and may reduce its effectiveness. Results of 17 consecutive cases of spontaneous pneumothorax treated thoracoscopically without pleurodesis are herein presented. No significant complications were encountered and no recurrences have been identified so far. Pleurodesis was omitted chiefly because it increases the morbidity of thoracoscopy. PMID- 1637618 TI - [Subtotal colectomy in splenic flexure carcinoma in a patient with transverse colostomy who had undergone gastric resection (Billroth II)]. AB - The Authors report a case of subtotal colectomy for splenic flexure adenocarcinoma in a gastro-resected patient bearing a transverse colostomy. They underline the considerable technical difficulties encountered during dissection because of multiple adhesions related to the previous operations (gastrojejunostomy and transverse colostomy). In fact, a gastric resection according to Billroth II and an emergency colostomy for bowel obstruction had been performed 20 years and 30 days respectively prior to the present operation. Nevertheless, reconstructive steps resulted easier and faster with the use of staplers. PMID- 1637619 TI - [Nerve-sparing cystectomy and ileal bladder substitution]. AB - Nerve-sparing techniques and bladder substitution following radical cystectomy allow today to obviate functional sequelae once registered in this type of surgery. Intraoperative identification of the pelvic plexus, which provides autonomic innervation to the corpora cavernosa, is necessary to preserve sexual function. Ileal orthotopic bladder substitution with preservation of the distal urethral sphincter assures a micturition per urethram and the urinary continence. The Authors report their experience with the Studer and Zingg procedure (ileal orthotopic bladder reservoir) performed in 26 cases. Results, technique, complications, and long-term evaluation are stressed. PMID- 1637620 TI - [Technique and immediate results of the Moreno Gonzalez-Carboni reconstruction after total gastrectomy]. AB - Reconstruction following total gastrectomy for gastric cancer is still matter of debate. The Roux-en-Y esophagojejunostomy and the interposed loop esophago jejunoduodenostomy are the techniques commonly employed. The Authors describe their modification of Henley's jejunal interposition and report early results achieved in a series of 60 consecutive patients. PMID- 1637621 TI - [Use of the Ravo bypass in high-risk colonic anastomoses]. AB - The Authors report a case of high risk colonic anastomosis treated by intracolonic by-pass procedure. The technique of Coloshield application is described. Its use prevents fecal contamination of the anastomotic site and, in case of dehiscence, anastomotic fistula formation. PMID- 1637622 TI - [Esophageal anastomosis using a stapler: new technical variants]. AB - Stapling techniques are considered the safer alternative for esophageal anastomosis in the Authors experience. In order to further improve results they suggest stapled esophageal anastomoses should be constructed avoiding purse string sutures and the use of purse-string devices or Satinsky forceps. PMID- 1637623 TI - [Mechanical trans-sutural colorectal anastomoses in the treatment of rectal cancer]. AB - The Authors report on 52 rectal cancers treated with anterior resection and mechanical anastomosis according to the Knight and Griffen technique. Such technique is quite practical, allows for easier sphincter-saving operations and is followed by a very low percentage of fistulas and anastomotic stenoses. In this series, a good anorectal function was restored in 6-12 months even in very low anastomoses; sexual complications were registered in 8% of cases; urinary troubles were not significant. The Authors conclude that the Knight & Griffen procedure is useful and advantageous. PMID- 1637624 TI - [The Soupault-Bucaillle operation in the treatment of Billroth II gastric resection syndrome]. AB - The study analyzes the benefits related to the gastroduodenojejunoplasty (GDJP) according to Soupault & Bucaille, adopted as the corrective treatment of the Billroth II gastric resection syndrome in those cases resistant to the dieting pharmacological supports. Our experience is based on 18 cases (13 males, 5 females, mean age 39 yrs), treated from 1982 to 1987 with GDJP for a gastric resection syndrome. The patients were observed 5 years after their resection: 10 presented with an atrophic gastritis/gastric atrophy and all had a diffuse acute phlogosis in presence of biliary storage. Manual anastomoses were performed in the first 8 cases, while staplers were used in the remaining cases. Results were quite satisfying; no operative mortality or specific complications, nor pain and biliary vomiting were registered; 14 patients over 18 (77%) gained weight significantly; only 1 patient reported low-intense early "dumping-like" symptoms easily controlled by medical therapy. Endoscopy showed no biliary reflux in all cases. Biopsies of the stump, carried on before and after the GDJP intervention, showed a marked reduction of the inflammatory aspects in 76% (13) of the patients. Among the 10 patients with atrophic gastritis/gastric atrophy, only 2 (20%) presented a significant increase in the number of gastric parietal cells and gastric principal cells. PMID- 1637625 TI - [Surgical staplers in thoracic surgery]. AB - Since its introduction in our department, in 1987, stapling devices are used on routine basis for thoracic surgery. Overall, 133 operations were performed: 95 lobectomies, 30 pneumonectomies, and 8 bilobectomies. Stapled related complications consisting of bronchopleural fistula following right pneumonectomy were registered in 3 cases. The use of vascular staplers was never associated with complications, and no air leakages following stapled parenchymal sutures were observed. The advantages related to the use of stapling devices are represented by low air leakage and bleeding rates, reduced operative trauma, and reduced operating time. However, confidence with the techniques is needed to avoid regrettable consequences. PMID- 1637626 TI - [Use of surgical staplers in proctocolectomy with ileal pouch. Effects on immediate results]. AB - The immediate results of 37 restorative proctocolectomies are reported comparing morbidity of stapled vs manual procedures. The stapled technique is easier and faster but does not reduce the incidence of leakages and pelvic sepsis related to the ileal pouch. It seems, though, to be more useful in reducing the morbidity related to the ileoanal anastomosis. PMID- 1637627 TI - [Manual and stapled sutures in digestive surgery: a comparative evaluation]. AB - Results concerning 819 digestive sutures and anastomoses, 376 (45.9%) of which hand sewn and 443 (54.1%) stapled, are retrospectively analyzed. Comparative evaluation of the two techniques yielded better results for oesophageal and rectal anastomoses as well as duodenal stump closure mechanically performed. For intestinal anastomoses the two techniques showed similar results when performed in election, on the contrary, mechanical sutures fared significantly worse than hand-sutures in non elective surgery, with a morbidity of 30.9% vs 10.2% (p less than 0.05) and a mortality of 4.8% vs 0%. In conclusion, for esophageal, rectal and duodenal anastomoses staplers may be preferred, while for the intestinal anastomoses in non elective surgery hand-sutures should be preferred. PMID- 1637628 TI - [Surgical staplers in colorectal surgery: 10 years of experience]. AB - The Authors dissert on some technical details for a correct use of staplers in colorectal surgery. Surgical skill and technology assure always better results, nevertheless the experience and knowledge of the single surgeon must be a guide for further research. PMID- 1637629 TI - [Staplers and pulmonary surgery]. AB - The Authors report their experience with staplers (model T.A. 30) in lung surgery: 152 stapled sutures were, in fact, performed in the IV Surgical Department of the University "La Sapienza" of Rome, during the period 1980/90. The use of staplers assures a perfect closure and prevents granulomas due to suture materials in typical as well as atypical lung resections. PMID- 1637630 TI - [Transhepatic and mini-laparotomic approach in the embolization of the left gastric vein]. AB - The Authors depict the possibility to reduce the risk of variceal bleeding with the embolization of the left gastric vein through a transhepatic or mini laparotomic approach. Such treatment applied in 5 cases was effective: during a mean one-year follow-up no rebleeding was registered, while the stabilization of a satisfying haemodynamic state in relation to the chronic liver disease was observed. PMID- 1637631 TI - [J-pouch after total gastrectomy]. AB - The Authors report their initial experience with the construction of a J-pouch as restorative surgery following total gastrectomy (TG) for malignant neoplasms. In the last 10 months of the 1990 upon 52 interventions for gastric cancer 31 TG were performed, and in 13 cases a J-pouch on the proximal end of the jejunal segment was constructed. No mortality or specific morbidity was registered using the totally stapled technique. Within one month 3/4 of the patients had normal meals as far as quantity and quality; also the foamy regurgitation seemed to be minimal. The ease of the reconstructive technique and the short term results obtained encourage the use of such approach. PMID- 1637632 TI - [Clinical use of a new compression surgical stapler in surgery of the large intestine]. AB - The clinical experience with the use in colorectal surgery of a new compression anastomotic device developed by the Authors is reported. From May 1986 through June 1990, 95 patients underwent large bowel anastomosis using this device. Operations performed included 51 left hemicolectomies or anterior resections of the sigmoid and rectum, 23 left colon resections, 19 right hemicolectomies, and two total colectomies. Twenty-nine anastomoses were performed below the pelvic peritoneal reflection and 18.5% of them resulted less than 4 cms from the anal verge while 20% were located between 4.5 and 8 cms. Five (5.2%) intraoperative diverting colostomies were needed. The rings were evacuated postoperatively after a mean of 10.9 days with none or very little discomfort. Operative mortality was 1.0% (one patient died of myocardial infarction). Anastomotic complications included five (5.2%) clinical and four (4.2%) subclinical leakages. No haemorrhages or stenoses were observed. This initial clinical experience shows the anastomotic device is reliable and justifies further experimentation. PMID- 1637633 TI - [Rational and mini-invasive approach to the therapy in varicose syndrome: the C.H.I.V.A. treatment]. AB - The principles of the C.H.I.V.A. (Ambulatory conservative and haemodynamic therapy of venous insufficiency) procedure are reported. According to the Authors a careful haemodynamic evaluation of the venous system strictly correlates to the clinical and functional results. In their experience, in fact, results showed no variceal recurrence and a very low rate of complications. Therefore, the C.H.I.V.A. procedure is recommended for most of the patients with lower limb varices. PMID- 1637634 TI - [Roux-en-Y loop gastro-jejuno anastomosis]. PMID- 1637635 TI - [Use of surgical staplers in reconstruction of the digestive continuity after total gastrectomy. Our experience in the aged]. PMID- 1637636 TI - [Surgical staplers and preservation of the sphincter function in surgery of rectal cancer. Our experience with the Knight-Griffen technique in the aged]. PMID- 1637637 TI - [Knight-Griffen reconstruction after low anterior resection for rectal carcinoma: personal experience and technical notes]. PMID- 1637638 TI - [Intestinal recanalization after Hartman's operation: use of surgical staplers]. PMID- 1637639 TI - [Our experience in the use of surgical staplers]. PMID- 1637640 TI - [Total gastrectomy with lymph node excision and the Roux-Orr esophago-jejunal reconstruction: its role in the therapy of gastric cancer]. PMID- 1637641 TI - [Ligation of the renal pedicle with a surgical stapler]. PMID- 1637642 TI - [Ochsner's approach as alternative to thoraco-phreno-laparotomy (in some selected indications or needs)]. PMID- 1637643 TI - [Surgical staplers in ultra-low anastomoses in rectal carcinoma: technical problems]. PMID- 1637644 TI - [Recanalization of the colon using a surgical stapler P-CEEA: an aseptic personal method. Variants]. PMID- 1637645 TI - [Ileal reservoir and ileo-rectal anastomosis with surgical staplers]. PMID- 1637646 TI - [Use of new surgical staplers in the Knight-Griffen technique. Our experience]. PMID- 1637647 TI - [Use of surgical staplers in general surgery: 11 years of experience]. PMID- 1637648 TI - [Total gastrectomy in cancer: technical notes]. PMID- 1637649 TI - [Ambulatory surgery of varicocele]. PMID- 1637650 TI - [Proposal of a recanalization technique after Hartman's operation]. PMID- 1637651 TI - [Proposal of a colorectal anastomosis technique previous to evagination of the rectal stump]. PMID- 1637652 TI - [Proposal of a colorectal anastomosis technique without the use of tobacco pouch suture]. PMID- 1637653 TI - [Esophagojejunostomy a la Roux after total gastrectomy]. PMID- 1637654 TI - [Use of biological glue in the surgical treatment of sacrococcygeal fistulas]. PMID- 1637655 TI - Leprosy situation in the world and multidrug therapy coverage. PMID- 1637656 TI - World malaria situation in 1990. Part I. PMID- 1637657 TI - Children and tobacco. PMID- 1637659 TI - Host cell reactivation of gamma-irradiated adenovirus 5 in human cell lines of varying radiosensitivity. AB - DNA repair processes play an important role in the determination of radiation response in both normal and tumour cells. We have investigated one aspect of DNA repair in a number of human cell lines of varying radiosensitivity using the adenovirus 5 host cell reactivation assay (HCR). In this technique, gamma irradiated virions are used to infect cells and the ability of the cellular repair systems to process this damage is assayed by a convenient immunoperoxidase method recognising viral structural antigen expression on the cell membrane 48 h after infection. Reduced HCR was exhibited by radioresistant HeLa cells and by a radiosensitive neuroblastoma cell line, HX142. In contrast, an ataxia telangiectasia cell line, AT5 BIVA, did not show reduced HCR. On the basis of these results we can make no general conclusions about the relevance of HCR to cellular radiosensitivity. We have extended these studies to determine whether our cell lines exhibited enhanced viral reactivation (ER) following a small priming dose of gamma-radiation given to the cells before viral infection. No evidence for this phenomenon was found either in normal or tumour cell lines. PMID- 1637660 TI - Cardiotoxicity of commercial 5-fluorouracil vials stems from the alkaline hydrolysis of this drug. AB - The cardiotoxicity of 5-fluorouracil (FU) was attributed to impurities present in the injected vials. One of these impurities was identified as fluoroacetaldehyde which is metabolised by isolated perfused rabbit hearts into fluoroacetate (FAC), a highly cardiotoxic compound. FAC was also detected in the urine of patients treated with FU. These impurities were found to be degradation products of FU that are formed in the basic medium employed to dissolve this compound. To avoid chemical degradation of this antineoplastic drug, the solution of FU that will be injected should be prepared immediately before use. PMID- 1637661 TI - Antitumour responses to flavone-8-acetic acid and 5,6-dimethylxanthenone-4-acetic acid in immune deficient mice. PMID- 1637658 TI - Towards selective pharmacological modulation of protein kinase C--opportunities for the development of novel antineoplastic agents. PMID- 1637662 TI - Rearrangement of chromosome 1p in breast cancer correlates with poor prognostic features. AB - In a cytogenetic study of breast cancer biopsies, clonal abnormalities of chromosome 1p were identified in 56% (14) of 25 informative patients. Translocations predominated, involving 1p22 (n = 1), 1p35 (n = 1) or 1p36 (n = 10) breakpoints. Chromosome 1p abnormalities were associated with estrogen receptor (ER) negativity (P = 0.03, 2-tailed Fisher Exact Probability test), high histological grade (P = 0.02, 2-tailed Mann-Whitney U-test) and an unfavourable Melbourne Prognostic Score (NEPA P = 0.02, SEPA P = 0.04, 2-tailed Mann-Whitney U tests). These findings are consistent with the possibility that a gene located on chromosome 1p is implicated in tumour progression. PMID- 1637663 TI - Assessment of morbidity from complete axillary dissection. AB - The importance of axillary dissection as part of the primary surgical procedure in the treatment of operable cases of carcinoma of the breast is established. The morbidity of this procedure, however, is less well documented. A study of 126 women who had had full axillary dissection as part of their initial surgical treatment was undertaken to assess their degree of morbidity in terms of numbness, pain, weakness, swelling, and stiffness. Seventy per cent of cases complained of numbness, 33% of pain, 25% of weakness, 24% of limb swelling, and 15% of stiffness. Objective measurements confirmed decreased sensation in 81%, weakness in 27%, swelling in 10%, and stiffness in 10%. In no case were these symptoms described as severe, though they did have an effect upon the daily lives of 39%. The side effects of full axillary dissection are common and all women should be warned of them prior to surgery; however they are usually mild and therefore should not preclude this procedure as a part of definitive surgical treatment. PMID- 1637664 TI - Aromatase inhibition: 4-hydroxyandrostenedione (4-OHA, CGP 32349) in advanced prostatic cancer. AB - We report the use of the steroidal aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA, CGP 32349), in the management of patients with advanced, hormone resistant, prostatic cancer. Eighteen of 25 patients (72%) showed a subjective response, mainly in the form of pain relief and increased performance. There were no objective improvements. A tumour flare occurred in 17/25 (68%). Detailed endocrine studies were performed during treatment. These showed that suppression of serum oestradiol levels occurred in 19/25 (76%) of patients during treatment with 4-OHA. Serum levels of androstenedione increased in 9/14 patients (64%). Concentration of serum testosterone and 5 alpha-dihydrotestosterone were elevated in 3/14 (21%) and 2/11 (18%) patients respectively. There appeared to be no correlation between response or tumour flare and changes in steroid levels during treatment with 4-OHA. The mechanism of action of 4-OHA in palliating patients with advanced prostatic cancer remains obscure. 4-OHA or its metabolites may be acting on metastatic bone metabolism via effects on oestrogen related osteoclastic and osteoblastic activity. Further investigation of the effects of aromatase inhibitors on prostatic biology, and bone metabolism in patients with metastatic prostate cancer, would appear worthwhile. PMID- 1637665 TI - The assessment of in vivo somatic mutations in survivors of childhood malignancy. AB - The assessment of chromosomal mutations in children may provide information about aetiology and risk of second malignancies. A somatic cell mutation assay which determines variant erythrocytes lacking expression of an allelic form of the sialoglycoprotein, glycophorin A, was applied to samples from children before and after receiving potentially genotoxic therapy. Fifty-six children who had received treatment for their malignancy, 15 with malignancy but prior to treatment and 43 control children were assessed for the presence of No and NN mutant variant red cells. Control children had mean (s.d.) No and NN variant frequencies (Vf) of 9.5 (7.0) and 5.8 (3.3) x 10(6) erythrocytes respectively. Comparison between pre-treatment and control groups demonstrated that prior to chemotherapy, patients with paediatric malignancy do not have mutant frequencies significantly different from the normal population. Children who had received chemotherapy, with or without radiotherapy, showed a significant elevation of both No and NN variants over 10 years from the end of treatment. Exposure of children to radiotherapy or known chemical mutagens leads to an increased frequency of variant erythrocytes which is probably the result of in vivo somatic cell mutations. The long term implications have yet to be determined. PMID- 1637666 TI - The pharmacokinetic advantages of isolated limb perfusion with melphalan for malignant melanoma. AB - We describe melphalan pharmacokinetics in 26 patients treated by isolated limb perfusion (ILP). Group A (n = 11) were treated with a bolus of melphalan (1.5 mg kg-1), and in a phase I study the dose was increased to 1.75 mg kg-1. The higher dose was given as a bolus to Group B (n = 9), and by divided dose to Group C (n = 6). Using high performance liquid chromatography (HPLC) the concentrations of melphalan in the arterial and venous perfusate (during ILP) and in the systemic circulation (during and after ILP) were measured. Areas under the concentration time curves for perfusate (AUCa, AUCv) and systemic (AUCs) data were calculated. In all three groups the peak concentrations of melphalan were much higher in the perfusate than in the systemic circulation. The pharmacokinetic advantages of ILP can be quantified by the ratio of AUCa/AUCs, median value 37.8 (2.1-131). AUCa and AUCv were both significantly greater in Group B than in Group A (P values less than 0.01, Mann-Whitney). In Groups B and C acceptable 'toxic' reactions occurred but were not simply related to melphalan levels. Our phase I study has allowed us to increase the dose of melphalan to 1.75 mg kg-1, but we found no pharmacokinetic advantage from divided dose administration. PMID- 1637667 TI - The prognosis of breast cancer patients in relation to the oestrogen receptor status of both primary disease and involved nodes. AB - Nodal involvement is accepted as the best single marker of prognosis in breast cancer. However, there is little information on the sub-division of node-positive patients according to the oestrogen receptor status of the nodal tissue. We have previously reported (Eur. J. Ca. 1987, 23, 31) that, in almost all cases, involved nodes are only oestrogen receptor positive (ER+) in patients whose primary tumours are uniformly ER+. This paper presents clinical follow-up on a larger group of patients with node positive breast cancer. For each patient, both soluble and nuclear receptor concentrations were determined in three separate parts of the primary tumour and in at least one involved node (we have previously defined tumours which contained ER in all six fractions of the primary as HS++, those lacking receptor in some fractions as HS+- and wholly receptor negative tumours as HS--). Median follow-up time was 71.5 months. As expected, patients whose tumours were HS++ had a significant (P less than 0.008) survival advantage. More importantly, patients with ER in both the soluble and nuclear fractions of their involved nodes survived significantly (P less than 0.003) longer than those with ER- nodes. Thus, full oestrogen receptor status of involved nodes will give sufficient prognostic information when adequate primary tissue is not available. PMID- 1637668 TI - Increased activity of 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase in purified cell suspensions and single cells from the uterine cervix in cervical intraepithelial neoplasia. AB - The activities of 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase have been measured in squamous epithelial cells of the uterine cervix from normal patients and cases of cervical intraepithelial neoplasia (CIN). A biochemical cycling method, which uses only simple equipment and is suited to routine use and to automation, was applied to cells separated by gradient centrifugation. In addition, cells were examined cytochemically, and the intensity of staining in the cytoplasm of single whole cells was measured using computerised microcytospectrophotometry. Twenty per cent of cells in samples from normal patients (n=61) showed staining intensities above an extinction of 0.15 at 540 nm, compared to 71% of cases of CIN 1 (n=14), 91% of cases of CIN 2 (n=11) and 67% of cases of CIN 3 (n=15). The cytochemical data do not allow definitive distinctions to be made between different grades of CIN whereas the biochemical assay applied to cell lysates shows convincing differences between normal samples and cases of CIN. There are no false negatives for CIN 3 (n=14) and CIN 2 (n=10) and 11% false negatives for CIN 1 (n=9) and 14% of false positives for normal cases (n=21). The results of this preliminary study with reference to automation are discussed [corrected]. PMID- 1637669 TI - Recombinant human interleukin 4 (IL-4) given as daily subcutaneous injections--a phase I dose toxicity trial. AB - Recombinant Interleukin 4 was administered by subcutaneous injection at daily doses of 0.5, 1.0 or 5.0 micrograms kg-1 to nine patients as part of a Phase I Dose Toxicity Study. Dose limiting toxicity was reached at 5 micrograms kg-1 day 1. Symptoms of toxicity included fatigue, 'flu like symptoms and elevated liver enzymes. Modest but significant elevations of neutrophil and platelet counts occurred. No clear evidence of antitumour effects emerged although pain in metastatic lymph nodes and a small fall in myeloma paraprotein levels during dosing were observed. In vitro and murine in vivo studies indicate that patients with lymphoproliferative disease should be selected for Phase II trials. PMID- 1637670 TI - Patterns of risk of hereditary retinoblastoma and applications to genetic counselling. AB - A registry including information about nearly 1,600 cases of retinoblastoma diagnosed in Britain has been created at the Childhood Cancer Research Group. Cases have been classified as 'old germ cell mutation', 'new germ cell mutation' or 'sporadic non-hereditary'. For a population-based group of 918 cases diagnosed between 1962 and 1985 we have calculated the proportions of unilateral/bilateral and hereditary/non-hereditary cases. Bilateral cases represent 40% of the total number over this period; the proportion known to be hereditary is 44%, a higher proportion than has been reported elsewhere. By following up selected groups of cases, an estimate has been made of the proportions of siblings of retinoblastoma patients and offspring of survivors from retinoblastoma who are themselves affected with the disease. Where there is no previous family history, the risk for siblings of retinoblastoma patients of developing the disease is approximately 2% if the disease in the affected child is bilateral and 1% if it is unilateral, assuming that there are no other siblings; if there are unaffected siblings the risks for subsequent children are lower. Children of patients with hereditary retinoblastoma have a one in two chance of carrying the germ cell mutation and for those who are carriers the probability of developing retinoblastoma is very close to the accepted figure of 90% if the parents have bilateral retinoblastoma but probably less if they have the unilateral form. For children of patients not known to be carriers, the probability of developing retinoblastoma is estimated to be about 1%, considerably lower than the previously accepted figure of about 5%. Retinoblastoma kindreds consist mainly of bilateral cases but there is evidence that some kindreds have a high proportion of unilateral cases. The ways in which these findings may be used in conjunction with modern techniques of molecular biology for prenatal and postnatal genetic counselling are discussed. PMID- 1637671 TI - 'Macrophages' and their putative significance in human breast cancer. PMID- 1637672 TI - Serum methotrexate in childhood ALL. PMID- 1637673 TI - Autocrine stimulation of growth of AR4-2J rat pancreatic tumour cells by gastrin. AB - The control of cell proliferation by gastrin has been investigated in a rat pancreatic tumour cell line, AR4-2J. Exogenous gastrin, 10(-12) to 10(-8) M, stimulated cell growth of thymidine-synchronised AR4-2J cells cultured over 48 h in serum-free medium. Cell lysates of AR4-2J cells contained an average of 4.5 and 3.5 pg gastrin per 10(6) cells, when grown in serum-supplemented or serum free media, respectively, as revealed by radioimmunoassay. In serum-free medium, AR4-2J secrete 34 ng 1(-1) 10(-6) cells of gastrin over 48 h. Addition of an anti gastrin immunoglobulin preparation, but not control immunoglobulins, caused a maximum 52% reduction in cell growth. These data are consistent with an autocrine role for gastrin in the control of AR4-2J cell growth. These results were supported by studies with gastrin/CCK receptor antagonists. Six non-peptide gastrin/CCK receptor antagonists inhibited AR4-2J cell growth in a concentration related manner. The concentration required for 50% inhibition (IC50) of cell growth by the amino acid-derived antagonists proglumide (3.5 x 10(-3) M), benzotript (1.8 x 10(-3) M), loxiglumide (1.1 x 10(-4) M) and lorglumide (6.7 x 10(-5) M) were of the same order and significantly correlated with their IC50 for inhibition of 125I-gastrin binding to AR4-2J cells. Inhibition of cell growth by these antagonists was partially reversed by the addition of exogenous gastrin. In contrast, the IC50 for inhibition of cell growth with two benzodiazepine-derived antagonists, the CCK-B receptor antagonist L-365,260 (4.6 x 10(-5) M) and the CCK A receptor antagonist devazepide (1.7 x 10(-5) M) were two-three orders of magnitude greater than those required to inhibit gastrin binding (10(-8)-10(-7) M). The growth inhibitory effects of L-365,260 and devazepide were not reversed by exogenous gastrin suggesting these benzodiazepine-derived antagonists do not inhibit cell growth by interaction with gastrin receptors. The results are consistent with gastrin being an autocrine growth factor in AR4-2J cells, and that stimulation of cell growth is due to stimulation of the gastrin, rather than CCK-B, receptor sub-type. This study highlights that gastrin receptor antagonists warrant further investigation as agents to control growth of tumours, such as those from the gastrointestinal tract, which express gastrin receptors. PMID- 1637674 TI - DNA cell cycle distribution and glutathione (GSH) content according to circadian stage in bone marrow of cancer patients. AB - DNA cell cycle distribution and glutathione (GSH) content in bone marrow were measured both at daytime and midnight over single 24 h periods in 15 cancer patients. Between patients the S-phase demonstrated a difference from lowest to highest value of 700%, whereas the corresponding difference for the G2/M-phase was nearly 900%. The mean GSH content measured in the bone marrow at the two timepoints was 2.24 +/- 0.21 nmol mg-1 protein, range 0.91-4.19 nmol mg-1 protein. A statistically significant higher fraction of cells in S-phase and G2/M phase was found at daytime as compared to midnight when excluding the four patients with an abnormal circadian variation in cortisol. No significant temporal variation in total bone marrow GSH content was found, although a weak correlation between S-phase and GSH content was demonstrated (r = 0.42; P less than 0.05). This correlation was strengthened when not including the six patients with an abnormal cortisol pattern (4) and bone marrow infiltration (2) (r = 0.66; P = 0.005). Cells in S-phase demonstrated a positive correlation with cells in G2/M-phase (r = 0.64; P less than 0.0001). A negative correlation was found between GSH content and age (r = 0.53; P less than 0.005). Finally, a statistically significant positive correlation was demonstrated between cortisol and both S-phase and G2/M-phase (r = 0.57; P less than 0.001 and r = 0.38; P less than 0.05, respectively). The present study suggests a possibility of optimising cancer therapy and use of hematopoietic growth factors by determining individual average values and circadian stage dependent variation in bone marrow DNA cell cycle distribution. Furthermore, GSH content in bone marrow may predict this tissue's sensitivity to cytotoxic agents. PMID- 1637676 TI - Ataxia telangiectasia genes and predisposition to leukaemia, lymphoma and breast cancer. PMID- 1637675 TI - Role of cholecystokinin in dietary fat-promoted azaserine-induced pancreatic carcinogenesis in rats. AB - The role of cholecystokinin in dietary fat-promoted pancreatic carcinogenesis was investigated in azaserine-treated rats, using lorglumide, a highly specific cholecystokinin-receptor antagonist. The animals were killed 8 months after the start of treatment. Cholecystokinin, but not dietary unsaturated fat, increased pancreatic weight. Rats treated with cholecystokinin developed more acidophilic atypical acinar cell nodules, adenomas and adenocarcinomas than control animals. Rats maintained on the high-fat diet developed significantly more adenomas and adenocarcinomas than controls given a diet low in unsaturated fat. Lorglumide largely inhibited the enhancing effect of cholecystokinin, but not of dietary fat, on pancreatic carcinogenesis indicating that it is unlikely that the promoting effect of dietary unsaturated fat on pancreatic carcinogenesis is mediated via cholecystokinin. PMID- 1637677 TI - Lipid metabolism in cancer cachexia. AB - The effect of cancer cachexia on the oxidative metabolism of lipids has been studied in mice transplanted either with the MAC16 adenocarcinoma, which induces profound loss of body weight and depletion of lipid stores, or the MAC13 adenocarcinoma, which is the same histological type, but which grows without an effect on host body weight or lipid stores. While oxidation of D-[U-14C]glucose did not differ between animals bearing tumours of either type and non-tumour bearing controls, oxidation of [1-14C]triolein administered by intragastric intubation was significantly (P less than 0.05) higher in animals bearing the MAC16 tumour than in either non tumour-bearing controls or in animals bearing the MAC13 tumour. Intestinal absorption of [14C]lipid was significantly (P less than 0.05) reduced in animals bearing the MAC13 tumour when compared with either non tumour-bearing animals or MAC16 tumour-bearing animals, but was not significantly different in the latter two groups. The level of labelled lipids in heart and adipose tissue after an oral [14C]lipid load was significantly lower in animals bearing the MAC16 tumour compared with the other two groups. The level of tumour lipids was also higher in the MAC16 than in the MAC13 tumour after both an oral [14C]lipid load or by direct injection of [U-14C]palmitate complexed to albumin into epididymal fat pads. Oxidation of [U-14C]palmitate was also significantly enhanced in liver and heart homogenates from animals bearing the MAC16 tumour. These results suggest that in cachectic tumour-bearing animals mobilisation of body lipids is accompanied by an increased utilisation. PMID- 1637678 TI - Reversal of multidrug resistance by surfactants. AB - Cremophor EL, a pharmacologically inactive solubilising agent, has been shown to reverse multidrug resistance (MDR). Using flow cytometric evaluation of equilibrium intracellular levels of daunorubicin (DNR), we found that eight other surface active agents will also reverse MDR. All the active detergents contain polyethoxylated moieties but have no similarities in their hydrophobic components. The properties of three polyethoxylated surfactants that showed the lowest toxicities, Cremophor, Tween 80 and Solutol HS15, were examined in more detail. The concentrations of Tween 80 and Solutol required to reverse DNR exclusion were 10-fold lower than for Cremophor. However while concentrations greater than or equal to 1:10(2) of the former two surfactants resulted in breakdown of cells, even 1:10 of Cremophor did not lyse cells. Studies of the effects of Cremophor on the uptake and efflux of DNR in normal and MDR cell types showed that Cremophor increases intracellular DNR primarily by locking the rapid efflux from the cells. This blockage of drug efflux may be mediated by a substantial alteration in the fluidity of cell membranes induced by Cremophor, as shown by decreased fluorescence anisotropy of a membrane probe. Consistent with these data, coinjection of adriamycin plus Cremophor into mice carrying a multidrug resistant P388 transplantable tumour significantly increased the survival time of the mice compared with adriamycin treatment alone. PMID- 1637679 TI - In vitro interaction of lithotripter shock waves and cytotoxic drugs. AB - The effect of a combination of lithotripter shock waves and cytotoxic drugs was examined in vitro. L1210 cells in suspension were exposed to shock waves during incubation with cislatin, doxorubicin, daunorubicin, THP-doxorubicin, or aclacinomycin. Proliferation was determined using the 3-4,5 dimethylthiazol-2,5 diphenyl tetrazolium bromide assay. Dose enhancement ratios were calculated for each drug in order to determine the effect of the additional exposure to shock waves. In addition, partition coefficients and IC50s of the drugs were determined. It was found, that the dose enhancement ratios increased for the drugs with decreasing cytotoxicity. The effect of all five drugs was enhanced by shock waves to a higher degree at 7 min incubation as compared to 50 min incubation. The effect of cisplatin was most significantly enhanced, with a dose enhancement ratio of 6.7 at 7 min incubation. The enhancement increased with the operating voltage used for generating the shock waves, and was only present when cells were exposed to shock waves during the incubation with the drug. An increase in cellular membrane permeability is proposed as the mechanism of interaction between shock waves and drugs. PMID- 1637680 TI - In vivo measurement of the association constant of a radio-labelled monoclonal antibody in experimental immunotargeting. AB - Exploring the fundamental mechanisms behind the low tumour uptake of labelled monoclonal antibodies (MoAbs) during in vivo immunotargeting, experiments were performed to estimate the in vivo value of the association constant (Ka) in an experimental targeting reaction. An artificial tumour model was utilised, based on diffusion chambers (DC) filled with antigen-coated polymer particles, implanted i.p. in normal, immunocompetent mice (NMRI/BOM). The MoAb H7 with specificity for placental alkaline phosphatase (PLALP) was chosen for this experiment. Each mouse carried two DC, one target DC filled with PLALP-coated particles, and a second control DC with the same amount of uncoated particles. The DC contained escalating doses of particles, ranging from 0.1 mg to 16 mg per DC, with groups of 6-12 animals per dose level. The next day after the implantation, a constant dose of 125I-labelled Fab fragments of H7 was injected i.v. in each mouse. The association constant Ka as measured from the binding data obtained in vivo was not significantly different from the value measured in vitro when the same target DC were incubated with the 125I-Fab in test tubes. This indicates that in vivo impairment of the antibody avidity is not the reason why a relatively low tumour uptake is generally experienced in immunotargeting studies. PMID- 1637681 TI - Normal human breast xenografts activate N-nitrosodimethylamine: identification of potential target cells for an environmental nitrosamine. AB - Normal human breast tissue maintained as xenografts in female Balb/c (nu/nu) athymic mice is capable of metabolising N-nitrosodimethylamine (NDMA) to active intermediates that will react with DNA. Administration of NDMA to mice with slow release implants of 17 beta-oestradiol which provide human physiological (luteal phase) circulating oestrogen levels and increase cell proliferation in the xenograft (Laidlaw et al., 1992), leads to an apparent increase in the extent of reaction with DNA compared to controls without oestrogen implants. In mice with oestrogen implants, measurements of the amounts of the promutagenic lesion, O6 methyl-2'-deoxyguanosine formed in DNA clearly indicated a dose related increase in the extent of reaction. Detection of O6-methyl-2'-deoxyguanosine using immunohistochemical procedures revealed that the nuclei of cells of the glandular epithelium, supportive tissue and adipose tissue, in decreasing order of prevalence, were positively stained for the presence of this DNA lesion. Epithelial cells, which are the putative target cells for carcinogenesis in the breast, are therefore prone to promutagenic damage as a result of exposure to an environmental nitrosamine. PMID- 1637683 TI - Relationship of myc protein expression to the phenotype and to the growth potential of HOC-7 ovarian cancer cells. AB - In this investigation we demonstrate expression of myc oncoproteins in HOC-7 ovarian adenocarcinoma cells. The cells were exposed to differentiation inducing agents such as dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), retinoic acid (RA) and transforming growth factor-beta 1 (TGF-beta 1). Myc protein expression in treated cells was then compared with that in control cultures and in monoclonal HOC-7 sublines, which are characterised by distinct phenotypes. Cells exposed to DMSO and DMF became markedly enlarged and flattened and developed cytoplasmic extensions. They looked similar to a subline, which revealed a less malignant and more differentiated cell phenotype. All four inducers prolonged the cell doubling time and reduced the saturation density to levels, normally found in the more differentiated subline. Furthermore, all inducers except RA elevated extracellular fibronectin, which is characteristic for less malignant epithelial cell phenotypes. All four agents inhibited myc oncoprotein expression reversibly (1% DMSO greater than 0.5% DMF greater than 10 microM RA greater than 10 ng ml-1 TGF-beta 1) and in time-dependent manner. Down regulation of myc protein expression is, therefore, closely related to inducer dependent growth reduction of HOC-7 cells and to the development of a less malignant cell phenotype. PMID- 1637682 TI - Effect of epidermal growth factor in HLA class I and class II transcription and protein expression in human breast adenocarcinoma cell lines. AB - The spontaneous expression of HLA class I and class II molecules in two human breast carcinoma cell lines (MCF7, T47D) and their modulation during epidermal growth factor treatment are reported. Transcription was analysed by Northern blot and hybridisation with HLA class II and class I cDNA specific probes. The expression of cell surface determinants was examined by internal protein labelling with 35s-methionine, immunoprecipitation with monoclonal antibodies specific for HLA class I or class II, followed by isolation of the immune complex on protein A-Sepharose; at least a quantification of glycoprotein was performed by chromatofocusing. Glycoprotein quantification showed a significant increase of HLA class I and class II (DR) antigen expression after stimulation by epidermal growth factor (0.02 microgram ml-1) in the two cell lines, when compared with untreated cell controls. However, with epidermal growth factor treatment of MCF7 and T47D cells, low increases in the amounts of HLA class I and class II RNA were obtained. These differences between expressed antigens and correspondent RNA amounts would be explained by the fact that EGF in these two cell lines acts more in post-transcription for HLA class I and class II antigens. PMID- 1637684 TI - Early and late changes in the normal mouse bladder reservoir function due to irradiation and cis-DDP. AB - Early and late changes in the reservoir function of the mouse bladder were investigated after radiation alone or a combination of radiation and cisplatinum (cis-DDP). Bladder function was investigated by repeated cystometries. Treatments consisted of either single fraction radiation (5-10-15-25-30 Gy) or 20 Gy in combination with cis-DDP (6 mg kg-1; i.p.) administered at various time intervals from 14 days before until 14 days after radiation. At two selected time intervals (15 min and 4 h before) radiation was given at different dose levels (5-10-15-20 Gy). Within 30 days after irradiation a dose-dependent early response was noticed both in the radiation alone group and the group where cis-DDP was administered 15 min before radiation. The dose-response curve showed a slight but non-significant shift to the left in the combined treatment group (dose effect factor (DEF) = 1.18). Investigation of the early change in bladder reservoir function in the animals treated with 20 Gy alone or a combination of 20 Gy plus cis-DDP at various intervals in relation to irradiation demonstrated a significant increase in response when cis-DDP was administered 24 h and 15 min before and 4 h, 72 h and 336 h after 20 Gy (P less than 0.05). The reversible nature of the early damage was demonstrated. Late response was irreversible and significantly increased in most groups were cis-DDP was administered from 168 h before until 72 h after compared to radiation alone. Comparing groups treated with radiation alone with groups where cis-DDP was administered 15 min and 4 h before radiation revealed DEF values up to 1.45 (P less than 0.05), reflecting the significantly larger response in combined treatment groups. Survival was significantly decreased in all combined treatment groups compared to groups treated with radiation only and likewise survival was decreased in the group treated by cis DDP alone compared to control (no treatment at all). PMID- 1637685 TI - Relations with parents and school and Chinese adolescents' self-concept, delinquency, and academic performance. AB - Current research and theory have suggested that the relational domains of family and school experiences are important to children's development. The present study thus examined how relations with parents and school were related to Chinese students' psychosocial and cognitive development in self-concept, delinquency, and academic performance. A total of 1668 secondary school students were studied, and results showed that better relation with parents was associated with higher general, academic, appearance, social, and physical ability self-concepts. Better relation with school was associated with higher academic performance, as shown in higher class rank, higher grand total exam scores, and higher scores in Chinese, English, mathematics, physical education, and music. Both poorer relations with parents and school were found to associate with more self-reported delinquency as well as more school records of misconduct. PMID- 1637686 TI - Shyness and education: the relationship between shyness, social class and personality variables in adolescents. AB - The study considers the relationship between shyness, some related personality variables and socio-economic status. Adolescent shyness levels are examined using two self-report questionnaires which cover the spectrum of inherent, emotional and situational shyness. These findings were correlated with individual levels of anxiety, neuroticism and also with socio-economic status. The educational implications of these results are discussed and the problem of the definition of shyness is addressed. The sample comprised 650 adolescents in the age range 11-18 years, drawn at random from two secondary schools, the number of boys being 300 and the number of girls 350. The results indicate that high levels of both situational and inherent shyness are related significantly to high levels of anxiety and neuroticism. Inherent shyness and situational shyness correlate only moderately with one another. Low levels of situational and inherent shyness are related positively and significantly to high levels of self-esteem and extraversion. Similar patterns of relationships occur for the other variables considered. The stability coefficients of correlations for each type of shyness were high after an interval of six months. Furthermore, shyness is related significantly to the socio-economic class of adolescents: a relatively higher percentage of shyness occurs among adolescents of lower socio-economic class. PMID- 1637687 TI - Sun protection with hats. AB - The degree of sun protection provided by various styles of hat at different anatomical sites on the head was measured using model headforms and ultraviolet sensitive film badges. It was found that hats with a small brim, such as the flat cap favoured by elderly male photosensitive patients, provided negligible protection at all sites apart from the vertex and forehead. Peaked baseball-style caps offer good protection to the nose but are relatively ineffective at other sites on the face. Hats with a wide (greater than 7.5 cm) brim are necessary in order to provide reasonable protection factors (greater than 3) around the nose and cheeks. PMID- 1637689 TI - Smoking habits in psoriasis: a case control study. AB - We have examined smoking habits in 108 patients with psoriasis, including some with palmoplantar distribution, and compared the results with matched controls from the community. There was a significant association between psoriasis, current smoking status (OR = 2.7, 95% CI 1.44-5.42, P less than 0.01) and smoking habits prior to the onset of disease (OR = 3.75, 95% CI 1.68-9.47, P less than 0.001). There was also a marked dose-response relationship; the relative risk of psoriasis in those currently smoking more than 20 cigarettes/day was significantly elevated (OR = 5.3, 95% CI 2.1-13.0, P less than 0.001). Separate analysis of patients without palmoplantar distribution of psoriasis showed a significant association with smoking prior to onset of psoriasis (OR = 3.6, 95% CI 1.5-9.8, P less than 0.001). Smoking may play a role in the aetiology of this common skin disorder. PMID- 1637688 TI - Psoriasis: an audit of patients' views on the disease and its treatment. AB - This audit aimed to establish the effect of out-patient clinic attendance on patients' attitudes to their psoriasis, its severity and its treatment. A secondary aim was to determine if there was any correlation between the patients subjective concept of disease severity and objective medical assessment. The audit was carried out by means of paired questionnaires completed by patients at their first visit to the out-patient clinic and at a review visit 3 months later. On each of these occasions an objective assessment of psoriasis severity score was made by the dermatologist. We were able to confirm previous reports of major psychosocial effects of psoriasis on the life-style of many patients. At their first visit 67% (30/45) of patients stated that their life-style was affected by psoriasis, while at review 3 months later this figure was 40% (18/45). Overall 76% (34/45) of patients felt their psoriasis had improved following attendance at the clinic, while 11% (5/45) of patients felt it had deteriorated over the 3 month period. However, all patients stated they found attendance at the out patient clinic to be of benefit. There was a significant correlation between the psoriasis severity score by the patient and by the dermatologist (P less than 0.001). PMID- 1637690 TI - Basal cell carcinoma in young adults. AB - The epidemiology and outcome of basal cell carcinoma (BCC) in adults aged 15-34 years were examined. Northern Region Cancer Registry data from 1979 to 1989 revealed a crude annual incidence of 37/100,000 total population and the incidence was constant in all age-groups during this period; 150 patients (1.2%) were aged 15-34 years. There was a small excess of females in the young age group. The outcome of BCC in young adults was determined using records of all patients registered over 5 years ago and additional information from family doctors where required. Patients with BCC in naevus sebaceous or with syndromes of which BCCs are a feature were excluded. Median duration of BCC pre-diagnosis was 3 years. Of 39 patients with completed 5-year follow-up data, 21% had either incomplete excision requiring further early treatment (n = 4), a later local recurrence (n = 2), metastatic BCC (n = 1) or a subsequent further primary tumour (n = 1); an additional three patients had two primary tumours at initial presentation. Median hospital follow-up was 12 months but the apparent disease free interval in patients with recurrent or new BCC was frequently over 2 years. BCC in young adults may not be suspected because it is uncommon. However, the high frequency of local recurrence and of multiple primary tumours indicates that careful follow-up is prudent in young patients with this tumour. PMID- 1637691 TI - Schopf-Schulz-Passarge syndrome. AB - Three siblings, the children of a marriage between first cousins, are reported with the characteristic ophthalmological and cutaneous changes of the Schopf Schulz-Passarge syndrome. There have been only eight reported cases of this disorder, and it has not previously been described in Great Britain. PMID- 1637692 TI - Sweet's syndrome responding to cyclosporin. AB - We report a case of Sweet's syndrome which responded to treatment with cyclosporin 4 mg/kg/day. Cyclosporin is effective in the treatment of many dermatoses, and although the immunosuppressive effects of cyclosporin are mainly attributed to inhibition of T-lymphocyte proliferation, it has also been shown to affect the functions of both neutrophils and monocytes. Possible mechanisms of action of cyclosporin in Sweet's syndrome are discussed. PMID- 1637693 TI - Successful treatment of steatocystoma multiplex by simple surgery. AB - Steatocystoma multiplex is usually a minor cosmetic problem but rarely can be extremely disfiguring. Unfortunately, the very patients who would benefit most from treatment are usually regarded as having too may cysts for surgery. We report a case of extensive steatocystoma multiplex which was treated by a simple surgical technique under general anaesthetic. PMID- 1637694 TI - Minimizing the risk of post-operative pyoderma gangrenosum. AB - A 61-year-old woman with seropositive rheumatoid arthritis developed numerous ulcers due to pyoderma gangrenosum at suture entry/exit sites following an arthroplasty of the right hip when interrupted silk sutures were used to close the skin. When a subsequent arthroplasty was performed on the left hip and subcuticular Dexon sutures were used to close the skin only two small ulcers developed. Sixteen cases of pyoderma gangrenosum developing in surgical wounds have previously been reported. We recommend that surgery in patients with a history of pyoderma gangrenosum is performed when the pyoderma is clinically quiescent, and that subcuticular sutures are used for skin closure, thus avoiding puncturing the skin surface. PMID- 1637695 TI - Systemic and cutaneous plasmacytosis with multiple skin lesions and polyclonal hypergammaglobulinaemia: significant serum interleukin-6 levels. AB - We report two patients who developed benign plasmacytosis with multiple skin lesions. The cases were characterized by hyperplasia of mature plasma cells, and polyclonal hypergammaglobulinaemia. One patient had hyperplasia of mature plasma cells not only in the skin, but also extensively in lymph nodes and the retroperitoneal areas around the ureters. The other had plasma cell hyperplasia limited to the skin. Extensive investigations failed to reveal any clinical or laboratory evidence suggesting the presence of any underlying disease accompanying the hypergammaglobulinaemia and/or plasma cell proliferation, such as chronic infectious disease, collagen disease or other chronic inflammatory disorder. Clinically and histologically, the first patient showed features compatible with a diagnosis of systemic plasmacytosis and the second with a diagnosis of cutaneous plasmacytosis. Significant serum interleukin-6 (IL-6) levels were detected in both patients, suggesting that IL-6 may be involved in the pathogenesis of these conditions. PMID- 1637696 TI - A comparison of the efficacy and relapse rates of narrowband UVB (TL-01) monotherapy vs. etretinate (re-TL-01) vs. etretinate-PUVA (re-PUVA) in the treatment of psoriasis patients. AB - Forty-five patients with extensive chronic plaque or guttate psoriasis were treated with either narrowband (TL-01) phototherapy, etretinate TL-01 combination therapy (re-TL-01) or etretinate and PUVA (re-PUVA) (15 patients in each group). Re-PUVA was the most effective therapy with 100% satisfactory clearance rate. TL 01 monotherapy had an 80% success rate; the relapse rate compared favourably with re-PUVA (50% in remission after 6 months). In the etretinate-TL-01 group, there was a 93% success rate and a one-third reduction in the total irradiation dose (8.0 J/cm2 vs. 12.7 J/cm2) but the relapse rate was higher, only 33% remaining in remission after 6 months. PMID- 1637697 TI - Mycosis fungoides with a widespread follicular eruption, comedones and cysts. PMID- 1637698 TI - Familial occurrence of crusted (Norwegian) scabies with adult T-cell leukaemia. PMID- 1637699 TI - Successful interleukin-2 therapy of advanced cutaneous T-cell lymphoma. PMID- 1637700 TI - Capillary leak syndrome in generalized pustular psoriasis. PMID- 1637701 TI - Successful treatment of ulcerating livedo reticularis with infusions of prostacyclin. PMID- 1637702 TI - Allergic contact dermatitis to calcipotriol. PMID- 1637704 TI - 72nd annual meeting of the British Association of Dermatologists. Bournemouth, 1 4 July 1992. Abstract. PMID- 1637703 TI - Severe lichen planus clears with very low-dose cyclosporin. PMID- 1637705 TI - Dust exposure and pneumoconiosis in a South African pottery. 1. Study objectives and dust exposure. AB - Dust exposure and pneumoconiosis were investigated in a South African pottery that manufactured wall tiles and bathroom fittings. This paper describes the objectives of the investigation and presents dust measurement data. x Ray diffraction showed that the clays used by the pottery had a high quartz content (range 58%-23%, mean 38%). Exposure to respirable dust was measured for 43 workers and was highest (6.6 mg/m3) in a bathroom fitting fettler. Quartz concentrations in excess of 0.1 mg/m3 were found in all sections of the manufacturing process from slip production to biscuit firing and sorting. The proportion of quartz in the respirable dust of these sections was 24% to 33%. This is higher than is usually reported in English potteries. Four hundred and six (80%) of the 509 workers employed at the pottery were potentially at risk of occupational lung disease. The finding of large numbers of pottery workers exposed to unacceptable dust concentrations is not surprising as poor dust control was found in all six wall tile and sanitary ware factories surveyed by the National Centre for Occupational Health between 1973 and 1989. Dust related occupational disease can be expected in potters for many years to come. PMID- 1637706 TI - Dust exposure and pneumoconiosis in a South African pottery. 2. Pneumoconiosis and factors influencing reading of radiological opacities. AB - A cross sectional radiological survey of workers exposed to pottery dust during the manufacture of wall tiles and bathroom fittings was conducted in a South African factory. Roughly one third of workers with 15 or more years of service in high dust sections of the factory had pneumoconiosis. Previously undiagnosed advanced cases, including two with progressive massive fibrosis, were working in dusty occupations. A firm diagnosis of potters' pneumoconiosis was made in 11 of the 358 workers radiographed; all had served more than 10 years suggesting that radiography of workers with more than 10 years service would be a successful case finding strategy in South Africa. A combination of rounded and irregular opacities was the most common radiological finding in the workers with pneumoconiosis (55%). Three readers reported on the chest radiographs, and all found an association between small radiological opacities, which were usually irregular or a combination of irregular and rounded, and exposure to pottery dust. The occurrence of irregular radiological opacities in workers exposed to pottery dust deserves further study. The least experienced reader significantly associated age with small opacities when duration of service (years) was used to measure exposure to dust. Sex was not an important predictor of radiological changes consistent with pneumoconiosis. Breast shadows were not an important cause of false positive readings and participating women did not develop pneumoconiosis after less exposure than men. PMID- 1637707 TI - Fibres and asbestos bodies in bronchoalveolar lavage fluids of asbestos sprayers. AB - The alveolar content of fibres and asbestos bodies was assessed by bronchoalveolar lavage (BAL) in 21 asbestos sprayers. Transmission and scanning electron microscopy (TEM and SEM) and two light microscopical (LM) methods, cytocentrifugation, and Millipore filtration were used. The subjects had been exposed mainly to crocidolite asbestos for an average of 2.8 (range 0.2-13) years in 1950-75. The mean (median) total fibre count (of asbestos bodies and uncoated fibres) per ml of BAL fluid was 5500 (2800) by TEM and 2900 (1000) by SEM. The mean (median) count of asbestos bodies per ml with LM was 810 (500) with cytocentrifugation and 750 (480) with Millipore filtration, 840 (320) by TEM, and 1750 (420) by SEM. The mean proportion of coated fibres was 35% by TEM and 45% by SEM. The mean length of the coated fibres was 22 (range 4-65) microns by TEM and 34 (range 4.5-170) microns by SEM. The total fibre count exceeded 1000 fibres per ml in 70% of the cases by TEM. Asbestos body counts exceeded 1 per ml in 95% of the cases by LM. The fibre counts by SEM were in good accordance with counts by TEM except in a few cases in which the TEM result was considerably higher. In these cases the proportion of coated fibres was also low. All four counting methods appeared to give consistent results in heavily exposed cases when fibre load in the lungs was high. The counting of asbestos bodies may, however, underestimate the total alveolar fibre load in some cases. PMID- 1637708 TI - Pulmonary impairment in workers exposed to silicon carbide. AB - Two hundred and sixty seven workers employed in the manufacture of silicon carbide (SiC) were examined to determine the effects of exposure to contaminants (SiC, quartz, and SO2) in the workplace on pulmonary function. No exposure concentrations exceeded the current permissible limits. Ten subjects (3.7%) showed rounded opacities (profusion greater than or equal to 1/0). Two subjects employed only in the final stages of the production process and not exposed to crystalline silica showed opacities (profusion q1/0 and q2/1) on x ray film suggesting a role of SiC in the genesis of interstitial lung disease. Chest abnormalities on x ray film were correlated with cumulative exposure to dust and pulmonary function was affected by cumulative dust exposure, profusion of opacities, and smoking. It is concluded that the current standards do not provide adequate protection against pneumoconiosis and chronic pulmonary disease in this industry. PMID- 1637709 TI - The aetiology of experimental fibrosing alveobronchiolitis induced in rats by paprika dust. AB - The effect of a single intratracheal dose of respirable paprika (Hungarian) dust, paprika dust extract, and cellulose dust on the lungs of rats was examined sequentially one and three months after a treatment. Treatment with respirable paprika and cellulose dusts resulted in alveobronchiolitis at the end of the first month and fibrotic changes at the end of the third month. As the extract of paprika dust caused no histopathological alterations, it is assumed that the high cellulose content of paprika was responsible for the histological reactions. PMID- 1637710 TI - Recent trends in bagassosis in Japan. AB - The only workers presently exposed to bagasse dust in Japan are the employees of sugar refineries and lacquerware factories. A follow up study of six former cases of bagassosis from among the retired employees of a paper board factory, closed since 1973, showed that none of the subjects still had bagassosis. Examinations of 70 employees of a sugar refinery for allergic reactions also showed no case of bagassosis. Seven cases with suspicious shadows of bagassosis on chest radiographs and four cases with positive serum precipitin to stored bagasse were, however, found among those 70 subjects. The results show the disappearance of a past episode of bagassosis and the possibility of a new occurrence of bagassosis among the employees of sugar refineries and lacquerware factories in the near future in Japan. PMID- 1637711 TI - Spontaneous abortion and work with visual display units. AB - OBJECTIVE: To determine whether women who work with visual display units are at increased risk of spontaneous abortion. DESIGN: Case-control study. SETTING: Women were recruited during the three years 1987-9 from the Royal Berkshire Hospital in Reading, and from a large group practice situated within the hospital's catchment area. SUBJECTS: Cases were 150 nulliparous working women with a clinically diagnosed spontaneous abortion and controls were 297 nulliparous working women attending for antenatal care. MAIN OUTCOME MEASURES: Cases and controls were contacted and personally interviewed using the same structured questionnaire. Exposure to visual display units (VDUs) at work was assessed from information supplied at interview. RESULTS: No evidence of an increased risk of spontaneous abortion was found in women who reported that they used a VDU at work compared with women who reported that they did not (odds ratio (OR) = 0.9, 95% confidence interval (95% CI) = 0.6-1.4); and no relation with the amount of time spent actively using a VDU was evident (OR = 0.9, 95% CI = 0.5-1.6 for women who worked with a VDU for 21 hours or more each week). No effect of passive exposure to VDUs at work was found (OR = 0.9, 95% CI = 0.6-1.6 for women who reported working less than 10 feet away from a VDU that was usually switched on). These findings were not explained by maternal age, marital state, housing tenure, partner's social class, educational level, smoking, alcohol consumption, or number of previous spontaneous abortions. CONCLUSION: Given the findings and their consistency with the results from other recent studies it is concluded that pregnant women who work with VDUs are not at increased risk of clinically diagnosed spontaneous abortion. For the many women who use VDUs in their jobs, this finding provides reassurance. PMID- 1637712 TI - Control of diabetes mellitus in shift workers. AB - OBJECTIVE: To determine whether the control of diabetes is different in insulin treated diabetic subjects who work shifts compared with those who do not work shifts and whether control is related to the type of shift worked. DESIGN: Prospective controlled study of 32 diabetic subjects working either regular days or shifts in a large car assembly factory. Insulin treated subjects who underwent a change in their pattern of shift work had diabetic control assessed before and six months after a change in shifts. MAIN OUTCOME MEASURES: Random plasma glucose, serum fructosamine, and haemoglobin A1 while at work. RESULTS: Diabetic control of insulin treated subjects who worked shifts was not significantly different from insulin treated subjects who worked days only. Diabetic control was poor in both groups and similar to that of diabetic subjects treated with oral hypoglycaemic agents. In those subjects that moved to a more rapidly rotating shift pattern there was a significant deterioration in control (serum fructosamine concentration before, 405 (SD 68); after, 481 (SD 90) mumol/l, p less than 0.01). CONCLUSIONS: The control of diabetes in insulin treated diabetic subjects who worked shifts was no worse than those who worked days only. Slowly rotating shifts were associated with better diabetic control than more rapidly rotating shifts. PMID- 1637713 TI - A prospective study of morbidity patterns in a petroleum refinery and chemical plant. AB - This study examined the morbidity experience from 1981 to 1988 of a prospective cohort of 3422 refinery and petrochemical plant employees from the Shell Deer Park manufacturing complex. The morbidity data for this study, which include all illness and absence records in excess of five days, were extracted from the morbidity section of the Shell health surveillance system. Standardised morbidity ratios (SMRs) of disease prevalence in this cohort were calculated using an internal comparison group of all manufacturing employees of the Shell Oil Company. Among production employees, the overall morbidity was statistically significantly higher (SMR = 109) than that of the comparison group. Illness due to hypertension (SMR = 144), haemorrhoids (SMR = 149), diseases of the nervous system (SMR = 120), respiratory system (SMR = 108), and digestive system (SMR = 117) were also raised for this group. The increased risk due to these medical conditions does not appear to be associated with occupational factors. Lymphatic and haematopoietic tissue neoplasms were raised (SMR = 124), but were based on only four cases. PMID- 1637715 TI - A cautionary note on the use of the correlation coefficient. PMID- 1637714 TI - Persistent asthma after accidental exposure to ethylene oxide. PMID- 1637716 TI - Polychlorinated biphenyls: estimated serum half lives. PMID- 1637717 TI - Two-level analysis of covariance structures for unbalanced designs with small level-one samples. AB - The main purpose of this paper is to develop basic statistical theory for two level analysis of covariance structures. Major asymptotic results for statistical inference, such as the asymptotic distributions of the estimator and the goodness of-fit test statistic are derived, based on an unbalanced design with only small numbers of level-one units. Computationally, it is shown that the solution can be obtained via standard programs, such as LISREL, EQS and COSAN. The behaviour of the estimates is illustrated by an artificial example and a real-life example. Some possibilities of extending the results to a more general two-level model, and to situations with arbitrary distributions and elliptical distributions are also investigated. PMID- 1637718 TI - Bayesian analysis of stochastic constraints in structural equation models. AB - Structural equation models are analysed in the presence of stochastic constraints. Based on a Bayesian perspective, a prior distribution on nuisance parameters in the unknown covariance matrix of error measurements with stochastic constraints is considered. An iterative procedure is implemented to produce the various Bayesian estimates with stochastic constraints. A simulation study is conducted to illustrate the accuracy and behaviour of this Bayesian approach. A real-life example is provided to illustrate the theory. PMID- 1637719 TI - The genomic organization and DNA sequence of the mouse vas deferens androgen regulated protein gene. AB - The gene for mouse vas deferens protein (MVDP) is expressed, under androgenic control, exclusively in the epithelial cells of the deferent duct. As a first step in correlating cell-specific and hormonal regulations with the structure of the gene, the complete sequence of the MVDP gene (11 kb) and 0.5 kb of the 5' flanking region have been determined. The size range for the 10 exons is 78 to 168 bp, whereas that of introns is 292 to 2833 bp. A major site of transcription is located on an A residue 46 nucleotides upstream from the A of the ATG initiation codon. A TATA (CATAA) box, a CAAT box, a GC-rich motif and a (5' TGTTCT-3') element that closely resembles the consensus sequence of the androgen response elements are present in the 5' flanking region of the MVDP gene. PMID- 1637720 TI - Loss of androgen dependency with preservation of functional androgen receptors in androgen-dependent mouse tumor (Shionogi Carcinoma 115). AB - Shionogi Carcinoma 115 (SC 115) is an androgen-dependent mouse tumor. Chiba Subline 2 (CS 2) is an androgen-independent subline derived from SC 115. CS 2 contains androgen receptors (AR), but is refractory to androgen and does not exhibit androgen-related responses which are observed in SC 115. In the present study the structure and function of AR in SC 115 and CS 2 are examined using cloned cells. There were no gross rearrangements or deletions in the AR genes of these cell lines when compared by Southern blot analysis with the AR gene in the mouse seminal vesicle. SC 115 and CS 2 expressed AR mRNA of normal size. When the cDNA containing DNA- and androgen-binding domains of the AR genes of both cell lines were amplified by polymerase chain reaction, no mutations were found in these regions. SC 115 and CS 2 were transfected with a plasmid containing a long terminal repeat of mouse mammary tumor virus linked to the chloramphenicol acetyltransferase (CAT) gene. Androgen stimulation of these transfectants resulted in equal elevation of CAT activity. These results indicated that the androgen-independent CS 2 contained functionally normal AR which were identical to those in the androgen-dependent parent tumor. PMID- 1637721 TI - Changes in the expression of cytochrome P450c17 associated with ovarian cystic follicles. An immunocytochemical and enzymatic analysis of porcine ovaries. AB - The steroidogenic activity of normal preovulatory and cystic follicles, and corpora lutea of porcine ovaries was investigated by immunocytochemical and radioenzymatic techniques. Using a specific antibody to porcine cytochrome P450c17, immunocytochemical staining was specifically localized in the theca interna layer of normal follicles and undetectable in the granulosa layer. The theca interna layers of non-luteinized cystic follicles were immunoreactive while those of luteinized follicles were not. Corpora lutea cells were essentially negative. The 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase activity was similar in luteinized cystic follicular and corpora lutea tissues, which had 8 times higher activity than found in normal preovulatory follicles. The formation of either corpora lutea or luteinized cysts led to a profound decline (12- to 15-fold) in 17 alpha-hydroxylase and 17,20 lyase activities compared to normal preovulatory follicles. In agreement with these enzyme findings, radioimmunoassays revealed very high levels of progesterone with nearly undetectable levels of androgens in the luteinized cysts. These studies demonstrate the functional similarities between cells of luteinized cysts and those of normal corpora lutea and suggest a pathology associated suppression of P450c17 expression in porcine cystic follicles. PMID- 1637722 TI - The ontogeny and cellular distribution of estrogen receptors in normal mouse mammary gland. AB - The appearance, epithelial and stromal cell distribution of estrogen receptors (ER) in normal mouse mammary gland were determined between 1 and 10 weeks of age using immunohistochemistry. The effect of ovariectomy and estrogen (E)-treatment on the distribution and concentration of ER-positive cells at various ages was also analyzed. These studies demonstrate that ER are present in both mammary epithelial and stromal cells before the mammary gland exhibits a proliferative response or increase in progesterone receptor concentration as a result of E treatment. Furthermore, an analysis of E-treatment suggests that although ER are present at an early age, there may be additional factors that determine the nature and extent of E-responsiveness. PMID- 1637723 TI - Low density lipoprotein-receptors in primary cultures of rat glial cells. AB - Newborn rat glial cells in primary culture contain an active cholesterol side chain cleavage cytochrome P450. Cholesterol can be supplied either by biosynthesis or derive from low density lipoproteins (LDL), which bind apolipoprotein Band E (apoB,E) (LDL)-receptors and undergo receptor-mediated endocytosis. Using antibodies to purified human plasma LDL and antibodies to bovine adreno-cortical LDL-receptor, the presence of LDL-receptors was demonstrated on rat glial cells after 3-4 weeks of primary culture, by ligand blotting, immunoblotting, and indirect immunofluorescence staining. The latter approach indicated that oligodendrocytes express higher levels of LDL-receptors than astrocytes present in the same culture. The immunofluorescence staining was observed not only at the cell surface, but also within the cytoplasm, suggesting that the LDL-receptor complexes had been internalized. Western blotting of LDL receptors extracted from glial cells indicated a band of approximately 130 kDa, the size expected for intact receptors. Their functionality was shown by the conversion of [3H]cholesterol linoleate, incorporated into reconstituted LDL and added to the cell cultures, to [3H]pregnenolone and/or its 20 alpha-hydroxy metabolite. This is the first characterization of functional LDL-receptors on isolated, well characterized, normal brain cells. PMID- 1637724 TI - Estrogen receptor affinity and effects on MCF-7 cell growth of triarylethylene carboxylic acids related to tamoxifen. AB - The estrogen receptor binding, and growth suppressant and stimulating effects in MCF-7 human breast cancer cells, of four structural variants of the triarylethylene antiestrogen tamoxifen (1) were studied. In these analogs, the dialkylaminoethoxy side chain of 1 was replaced by carboxylic acid or oxyacetic acid substituents. The presence of a p-hydroxy group in the ring geminal to the one bearing the side chain resulted in ligands with estrogen receptor affinities greater than that of 1 but less than that of estradiol. Compared to 1, none of the test compounds were effective suppressants of cell growth. To the contrary, the phenolic oxyacetic acid analog effectively reversed the growth suppressive effect of 1. Also, it was as effective as estradiol, though less potent, in stimulating growth of cells grown in estrogen depleted medium, suggestive of full estrogen agonist activity. Its carboxylic acid counterpart had little or no effect on proliferation. Because the phenolic oxyacetic acid is a metabolite of 1 in animals, its estrogenicity may have therapeutic implications of concern, depending on the extent to which it is formed and distributed in tissues of patients receiving 1. PMID- 1637725 TI - The effect of essential fatty acid deficiency on hepatic bile salt sulphotransferase in rats. AB - Hepatic bile salt sulphotransferase (BSS) activity and the contents of unconjugated oestradiol-17 beta (E2) and conjugated oestrone (cE1) in liver tissue was significantly lower in young essential fatty acid (EFA) deficient female rats than in female control rats. No corresponding differences were found between male EFA deficient and control rats. A significant sex difference, with higher values in females, was found for BSS activity and E2 and cE1 contents in control rats but not in EFA deficient rats. The decrease in hepatic BSS activity in female rats caused by EFA deficiency may be mediated via a decreased estrogenic action on the liver. PMID- 1637726 TI - The effects of sex hormone binding globulin (SHBG) on testosterone transport into the cerebrospinal fluid. AB - The movement of testosterone (T) from blood across the blood-brain barrier (BBB) is thought to reflect the combined effects of T's lipid solubility and the presence of circulating binding proteins for T such as albumin or sex hormone binding globulin (SHBG). Since the adult rat lacks a circulating specific high affinity sex steroid binding protein, examination of the disappearance from serum and uptake into cerebrospinal fluid (CSF) of [3H]T before and after SHBG or albumin infusion should provide insight into the function of these two proteins with respect T transport. Three groups of adult male Sprague-Dawley rats were cannulated at the femoral vein and cisterna magna. In a control group (n = 8), [3H]T was given as an intravenous bolus beginning at time zero; multiple serum and CSF collections were assayed for counts per min (cpm) during the subsequent 45 min. Data from these animals were then compared to those seen in animals that received either purified human SHBG (hSHBG) (n = 7) or human albumin (hALB) (n = 6) 10 min prior to the [3H]T infusion. High performance liquid chromatography was used to monitor the metabolic fate of the steroid infusate at the end of each study period. Infusion of hSHBG increased serum concentrations from undetectable to 93.8 nM/l (mean +/- SEM, n = 6). Administration of hALB significantly increased (25.0 +/- 1.2 g/l at baseline, 33.4 +/- 1.6 g/l post-infusion, mean +/- SEM, P less than 0.03, n = 5) the circulating albumin concentration. Comparison of data from each group of animals demonstrated that (1) following an i.v. injection of radiolabeled T, the initial decline in serum [3H]T was significantly reduced (P less than 0.03) in the presence of hSHBG, (2) hALB did not affect the movement of [3H]T out of serum, (3) the time to peak appearance of [3H]T in the CSF was significantly delayed (P less than 0.02) by the presence of circulating hSHBG, and (4) the net quantity of [3H]T found in the cSF under steady-state conditions was not affected by serum SHBG or albumin levels. This study demonstrates that high-affinity steroid binding proteins do modulate the transport of sex steroids across the BBB. Specifically, SHBG delays the clearance of T from serum and slows the rate of T uptake into the CSF during non equilibrium conditions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1637727 TI - Hydroxylation of 19-norandrogens by porcine Leydig cells. AB - The metabolism of 19-norandrogens by porcine Leydig cells was investigated. Non radioactive 19-norandrostenedione (19-Nor A) and [3H]19-nortestosterone (19-Nor T) were used as substrates in incubations with cell preparations from mature male pigs. Steroid products were separated by reversed-phase HPLC and material in selected peaks was rechromatographed before attempts to identify them by GC-MS. Both 11 beta- and 6 beta-hydroxylated derivatives of 19-Nor A were found and a third product (11-oxo-19-Nor A) was tentatively identified. The profile of radioactive metabolites from [3H]19-Nor T also favours the view of a capacity for hydroxylation of 19-norandrogens by porcine Leydig cells. The significance of these findings together with our earlier report of direct 11 beta-hydroxylation of C19 steroids by such cells remains to be examined. PMID- 1637728 TI - ATP-sensitive potassium channels and myocardial ischemia: why do they open? AB - There is evidence that the "ATP-sensitive" potassium channel opens, at least during the early stages of myocardial ischemia, despite relatively high ATP levels. Thus, channel opening may partially contribute to potassium efflux and accumulation of extracellular potassium, but probably much more profoundly to electrical abnormalities associated with ischemia, including the development of lethal arrhythmias. Several factors are discussed that may promote a significant open-channel probability of the channel, in spite of relatively high levels of ATP. It is argued that, even with a very low open probability, the magnitude of total membrane current carried by these channels may be substantial (comparable to other potassium currents) because of the high density and conductance of the ATP-sensitive potassium channel. Finally, it is shown how the ATP-sensitive potassium channel may play a role in various tissue types, ranging from the physiological to the pathophysiological. This potassium channel is therefore increasingly targeted for drug development and research. PMID- 1637729 TI - Role of timing of administration in the cardioprotective effect of fructose-1,6 bisphosphate. AB - We administered fructose-1,6-bisphosphate (FDP), 1 mM, to isolated and perfused rabbit hearts submitted, after 90 minutes of equilibration, to an ischemic period (60 minutes at a coronary flow of 0.17 ml/min/g), followed by a period of reperfusion (30 minutes at a coronary flow of 3.6 ml/min/g). FDP was delivered at different times following the experimental protocol: 60 minutes before ischemia and for the entire experiment; 60 minutes before and during ischemia, but not at reperfusion; at the onset of ischemia and during reperfusion; and only during reperfusion. The FDP cardioprotective effect was evaluated in terms of recovery of left ventricular pressure developed during reperfusion, creatine phosphokinase (CPK) and noradrenaline release, mitochondrial function (expressed as yield, RCI, QO2, ADP/O), ATP and creatine phosphate (CP) tissue contents, calcium homeostasis, and by measuring oxidative stress in terms of reduced and oxidized glutathione release and tissue contents. Our data show that the cytoprotective action of FDP is closely related to the time of administration. Optimal myocardial preservation was achieved when it was present prior to ischemia and during reperfusion. When given at the time of ischemia or only on reperfusion, FDP does not exert cardioprotection. The data suggest that the FDP cardioprotective effect is related to improvement of energy metabolism. PMID- 1637730 TI - Similar antiischemic effects of intracoronary atenolol and nifedipine during brief coronary occlusions in humans. AB - To compare the antiischemic effects of intracoronary administration of a beta blocker, atenolol, and of a calcium antagonist, nifedipine, on the clinical and electrocardiographic signs of myocardial ischemia induced by balloon occlusion of the coronary artery, we studied 32 consecutive patients undergoing routine PTCA. In each patient at least three balloon inflations were performed: the first served to verify the occurrence of ischemia (ST segment depression/elevation greater than 1.5 mm); the second was used as a control occlusion; the third was performed after the patients were assigned to receive either atenolol 1.0 mg IC (group 1, N = 16) or nifedipine V = 0.2 mg IC (group 2, N = 16). In a control population of 10 patients, the time to return to baseline of the ECG tended to be progressively shorter during the three consecutive inflations, but the other clinical and ECG parameters did not change significantly. In group 1 and group 2, two patients did not show ECG signs of ischemia at the third inflation; the time to ischemia increased in group 1 (+76%, p less than .001) and group 2 (+85%, p less than .01; NS group 1 versus group 2); ST segment displacement at 30 seconds decreased in group 1 (-38%, p less than .01) and group 2 (-36%, p less than .01; NS group 1 versus group 2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637731 TI - Enalapril versus combined enalapril and nadolol treatment: effects on blood pressure, heart rate, humoral variables, and plasma potassium at rest and during exercise in hypertensive patients. AB - The effect of enalapril alone and in combination with nadolol on resting and exercising blood pressure, heart rate, plasma renin activity, aldosterone, noradrenaline, and potassium levels was studied in 10 hypertensive patients (diastolic blood pressure between 95 and 114 mmHg). Patients received placebo for 4 weeks, enalapril (mean daily dose 24.5 mg) for 8 weeks, and nadolol, 40 mg once daily, was added for the remaining 8 weeks of the study. Exercise testing (modified Bruce, treadmill) was conducted at the end of the placebo run-in phase and at the end of each treatment period. Enalapril reduced resting and exercising blood pressure independent of any change in heart rate: This effect was increased with combination treatment. Plasma renin activity at rest and during exercise was increased by enalapril. Combination treatment attenuated this response and significantly reduced plasma aldosterone. Neither treatment had any effect on plasma noradrenaline levels. Resting plasma potassium levels were increased with combination treatment, whereas both treatment regimens increased plasma potassium levels during exercise. There were no clinically relevant episodes of hyperkalemia. Further investigation is required to qualify the nature of the blood pressure and plasma potassium response with combination treatment. PMID- 1637732 TI - Hibernating myocardium: a historical perspective. AB - Hibernating myocardium refers to the presence of persistent myocardial and left ventricular dysfunction at rest, associated with conditions of severely reduced coronary blood flow. This left ventricular dysfunction probably represents an adaptive mechanism preventing irreversible myocardial cell damage, since myocardial and left ventricular dysfunction in hibernating myocardium improve following the restoration of coronary blood flow. This review examines the evolution of the concept of hibernation from a clinical observation of the potential underlying mechanisms recently proposed. PMID- 1637733 TI - Hibernation and myocardial ischemia: clinical detection by positron emission tomography. AB - Regions of myocardium supplied by severely diseased epicardial arteries may develop chronic ischemia at rest and exhibit reduced contractility, contributing to a reduction in global left ventricular function. However, after revascularization, contractility in these regions may return to normal. These regions of asynergy are described as "hibernating myocardium." Such myocardium in which normal contractility may be restored often coexists with areas of infarcted, or scar, tissue, leading to the definition of hypoperfused hibernating myocardium as viable myocardium. It is important to identify viable myocardium, as revascularization of these areas should lead to the greatest improvement in left ventricular function and, thus, improvement in survival. Positron emission tomography is the best noninvasive method for quantifying regional myocardial blood flow and metabolism. Using 18F-fluorodeoxyglucose, which measures myocardial glucose utilization, it is possible to identify myocardial tissue that is hypoperfused at rest with preserved or increased glucose uptake. This mismatch of blood flow to metabolism has a high predictive accuracy in the recovery of contractile function. In order to reduce the need for metabolic imaging in documenting myocardial viability, a regional index of perfusable tissue derived from imaging with 15O water has been recently developed that also allows the quantification of tissue viability. PMID- 1637734 TI - Recovery of myocardial function in the hibernating heart. AB - Impaired contractile performance at rest is not necessarily due to irreversible tissue damage but may relate to the "hibernating" myocardium. Hibernating myocardium has been defined as potentially reversible, chronic contractile dysfunction during prolonged, painless ischemia. The extent and time course of functional recovery after restoration of flow is of major importance for clinical decision making. The existence of hibernating myocardium was first documented in patients following bypass surgery. Angiographic studies in patients undergoing coronary angioplasty revealed immediate recovery of global and regional systolic, as well as diastolic, function after revascularization. Subgroup analysis showed an improvement in patients without previous myocardial infarctions and in those with non-Q-wave infarctions, but a benefit was not consistently seen in patients with transmural infarctions. A further improvement of systolic function after 15 weeks suggests a biphasic course of recovery. Prospective studies must clarify whether the potential for improvement in function constitutes an indication for revascularization independent of clinical symptoms. PMID- 1637735 TI - Hibernating myocardium in patients with coronary artery disease: identification and clinical importance. AB - The term hibernating myocardium describes a particular outcome of myocardial ischemia in which myocytes show a chronically depressed contractile ability but remain viable. Revascularization of hibernating tissue causes a recovery of mechanical function that correlates with long-term survival. Therefore it is important clinically to distinguish hibernating from infarcted myocardium, since asynergies due to hibernation will improve on reperfusion, whilst those due to infarct will not. One suggested technique to identify hibernating myocardium is to stimulate the myocytes acutely, but briefly, by administration of inotropic agents while monitoring contractile function by echocardiography. We report our experience on the use of low dosages of dobutamine. Myocardial viability was validated by measuring the recovery in contraction of the akinetic areas after coronary artery bypass surgery by means of intraoperative epicardial echocardiography. The test has a sensitivity of 93% and a specificity of 78%. It is useful for identification of viable myocardium and also for quantification of intraoperative risk in individual patients. Limitations of this test are related to the presence of downregulation of beta receptors and to the impossibility of differentiating hibernating from stunned myocardium. Another useful technique of identifying hibernating myocardium is the use of radionuclear markers for viability. In our experience the two most important tests are (1) rest redistribution imaging of thallium 201 (which has a high sensitivity of 93% but a low specificity of 44%) and (2) 99mTc-Sestamibi imaging, which provides information on both perfusion and function with a single injection. This latter technique allows differentiation between stunning and hibernating on the basis of coronary flow which is preserved in stunning and reduced in hibernation. PMID- 1637736 TI - Survival in very low birthweight infants at the University of Port-Harcourt Teaching Hospital, Nigeria. AB - Between January 1984 and December 1987, 1509 singleton neonates were admitted into Special Care Baby Unit at the University of Port Harcourt Teaching Hospital; 29(1.9%) of these were Extreme Low Birthweight (ELBW), 86(5.7%) were Very Low Birthweight (VLBW), 406(26.9%) were Low Birthweight (LBW) and 988 (65.5%) were Normal Birthweight (NBW) infants. Survival rates in the four categories were 10.3%, 46.5%, 89.2% and 94.7% respectively. Factors which significantly influenced survival in the VLBW infants included higher mean birthweight (p less than 0.01) longer mean gestation (p less than 0.001) and lower incidence of birth asphyxia (p less than 0.02 with Yates's correction). Furthermore the survivors were significantly more mature for their gestation than those who died (p = 0.008, Fisher's Exact test). Care of the VLBW infant is not beyond the capabilities of Special Care Baby units in developing countries. In the light of our report, survival of Low Birthweight infants is a strong reflection of that of VLBW infants and survival of this category of babies could be improved by instituting general measures such as those aimed at reducing the incidence of LBW in the environment and by specific measures like carrying out prompt and effective resuscitation of the asphyxiated neonate and preventing sepsis. PMID- 1637737 TI - The pattern of human intestinal helminth infections in farming communities in different parts of Ondo State, Nigeria. AB - Faecal samples collected from people inhabiting project areas of Owena River Basin and Rural Development Authority at Okitipupa, Akure Ifon and Ajowa which are located in different geographical areas of Ondo State, Nigeria, were examined for helminth ova and larvae. The common worms were Ascaris lumbricoides, Trichuris trichiura and hookworms with average occurrences of 43.1% 23.4% and 17.0% respectively. Infections were highest in subjects in the age groups of 6-10 and 11-15 years and lowest in those over 25 years. The frequency of occurrence of Ascaris and Trichuris were high in all towns. Hookworms infection rates were 24.6%, 19.7%, 21.5% and 2.1% at Akure. Ifon, Ajowa and Okitipupa respectively. The low hookworm incidence at Okitipupa which is near the coast has been attributed to the heavy soils of clay and silt coupled with heavy rainfall. PMID- 1637739 TI - Primary peripheral lymphadenopathy in Jos, Nigeria. AB - Surgical biopsy specimens of 129 enlarged peripheral nodes seen at Jos University Teaching Hospital over a 3-year period were analyzed. Enlarged peripheral nodes due to primary sarcomas or carcinomas were excluded from the series. Tuberculosis and malignant lymphomas were diagnosed in 48.0% and 28.8% of the patients respectively. Amongst children aged 12 years and below, these diseases account for 50.0% and 30.0% childhood primary peripheral lymph node enlargement respectively. Non-diagnostic features were seen in 20.8% of patients. The cervical (53.0%), axillary (18.2%) and inguinal (7.4%) nodes are affected in that order. Regional lymph node involvement is the usual pattern. PMID- 1637738 TI - Another look at the nephrotic syndrome in adult Nigerians: pathological and immunological findings. AB - One hundred and twenty adult Nigerians with the nephrotic syndrome were subjected to similar pathological investigations which included light microscopy and immunoperoxidase study of renal biopsy specimens, serum immunoglobulins and C3c levels. Histological findings showed a wide range of changes with the minimal change type of lesion and proliferative glomerulonephritis accounting each for 33.3 percent of cases studied. Focal changes accounted for 26.3 percent of cases. Glomerular immune deposits were present in 78.6 percent of cases showing non minimal change glomerular lesions. Serum IgG and IgA were significantly depressed when compared with matched controls (P less than 0.05 and P less than 0.01 respectively) while IgM levels were significantly increased, (P less than 0.001). There was no significant difference between the mean values of serum C3c in the nephrotic group and matched control group. This study shows the high incidence of minimal change nephropathy in our adult population. Although some immunoglobulin (especially IgM) may be identified in occasional glomeruli and cause uncertainty as to the diagnosis, such minor deposition of IgM which is often non specific does not preclude a diagnosis of minimal change nephropathy. PMID- 1637740 TI - Radiological assessment of the patella position in the normal knee joint of adult Nigerians. AB - A method of determining the patella position as described by Insall and Salvati (1971) was re-evaluated. Lateral radiographs of 300 normal knee joints were obtained. The length of the ligamentum patellae was compared with the patella length. Both measurements were found to be approximately equal and the normal variation did not exceed 20%. The ratio of the length of the ligamentum patellae to the diagonal length of the patella was found to be a useful index in determining Patella height (position). Clinical value of these measurements are also discussed. It is therefore believed that these ratios irrespective of racial differences, are relatively simple, practical and reproducible. The Insall and Salvati method should therefore be preferred to other previously described methods of determining patella position. PMID- 1637741 TI - Epidemiological survey of an outbreak of gastroenteritis in a rural community in Oyo State. AB - This report documents the investigation and control of an outbreak of gastro enteritis in Lagun, Oyo State, Nigeria. Prior to the outbreak which occurred in 1981, there had been epidemics of gastro-enteritis, suspected to be cholera, in various parts of Nigeria. The investigations carried out included personal interviews of patients and their contacts, laboratory investigations of faecal specimens and analysis of water samples obtained from the village wells and stream. Available evidence indicates that the infection was probably introduced by one of the many visitors who had thronged the village for a festival. Neither Vibrio cholerae, Salmonella nor Shigella species were isolated from fecal specimens. However Vibrio metschnikovii organisms were present in water from the stream; and all the water samples tested revealed faecal contamination. The intervention consisted of intensive health education of various groups in the community, chlorination of water sources, treatment or referral of patients as necessary, with chemoprophylaxis and cholera immunization for contacts. A community environmental sanitation programme was also carried out, and recommendations have been made. This study highlighted what can be done at Primary Health Care level to investigate and control epidemics of gastro enteritis which are common occurrence in the rural communities of this country. PMID- 1637742 TI - The orthogonal electrocardiogram in adult Nigerians: a preliminary report. AB - The Orthogonal ECG (Frank Lead System) was analysed in 664 asymptomatic normal Nigerians (333 Males: 331 Females) aged 15 to 90 years (mean: 39.1 +/- 16.7). The system gave the same information as the 12-Lead EGG concerning the heart rate and rhythm, durations of waves, intervals and segments, J-point elevation and ST-T variants. QRS morphology was of the left ventricular pattern with the Rs greater than R greater than qRS greater than qR patterns dominating the scene in X and Y leads, and QR much greater than qR in 2. All these suggest that the cardiac vector is oriented leftwards, inferiorly and posteriorly. There was no QS pattern in any lead. There was no Sx dominance, and no S wave in Z. Septal Q, recorded in 29.2% of X and 25.1% of Y did not exceed 0.3 seconds and 2 mm. There was no Tx or Ty inversion. Rather, they were upright (98.3% and 95.9% respectively) and rarely flat (1.7%:4.1%). The Orthogonal ECG is recommended as a simple, accurate system for clinical use either as a supplement to or in lieu of the 12-lead system. PMID- 1637743 TI - Short stature at the University College Hospital, Ibadan, Nigeria. AB - Twenty four patients were evaluated for short stature at the University College Hospital, Ibadan, Nigeria, over a seven year period. Fourteen were males, 10 were females and their ages ranged from 6 to 23 years at first presentation. Nine out of the 10 females came to the hospital primarily because of failure of sexual development whereas only 1 of the 14 males presented with this complaint. The causes of short stature were as follows: idiopathic hypopituitarism in 5 (20.8%) patients (4 males, 1 female), gonadal dysgenesis in 5 patients (all females), syndrome of hepatosplenomegaly, dwarfism and poor sexual development in 5 patients (all males); 2 (8.3%) patients had hypothalamic-pituitary lesions, 2 had juvenile hypothyroidism and 1 (4.2%) had sickle cell hemoglobinopathy; the cause of the short stature was not certain in 4 (16.7%) patients. This is perhaps the first time that the syndrome of hepatosplenomegaly of uncertain etiology with delayed growth and sexual maturation previously reported in Iranian and Egyptian adolescents, is being described in black Africans. Although comprehensive hormonal data were not available in most of these patients, this clinical descriptive study is the first attempt at reporting some of the causes of short stature in Nigerians. PMID- 1637744 TI - Congenital malformations of the central nervous system at the Jos University Teaching Hospital, Jos Plateau State of Nigeria. AB - The pattern of congenital malformation of the central nervous system (CNS) as seen in Jos University Teaching Hospital (JUTH) is slightly different from that seen in Europe, Japan and Southern Nigeria. Not all the various types of CNS malformations reported from these centres have been seen in JUTH. Myelomeningocele was the commonest anomaly of the CNS seen and it accounted for more than 60% of all cases. Bilateral talipes equinovarus deformity was the commonest associated anomaly found. No case of anencephaly was seen in this study. PMID- 1637745 TI - Tropical splenomegaly syndrome in Nigerian adults. AB - Thirty-nine Tropical Splenomegaly Syndrome (TSS) patients. 19 males and 20 females, aged 13 to 69 years, with a mean age of 44.4 years, seen over a two-year period, January 1987 to December, 1988, at the consultant Medical Out-patient Clinics of the University of Nigeria Teaching Hospital, Enugu, Nigeria, were retrospectively studied. The aetiopathogenetic basis of the syndrome was briefly reviewed. The implications of the probable extent of this medical problem TSS in the tropics was emphasized. The spectrum of clinical presentation, haematological picture and results of other investigations were reviewed. An attempt was made to possibly distinguish TSS from such other similarly presenting conditions as Hodgkin's Lymphoma, Chronic granulocytic leukaemia and Chronic lymphocytic leukaemia, on clinical grounds and simple laboratory data that can be easily available to the tropical physician. The probable complications of TSS, the ease of treatment and the impressive results of therapy were highlighted. The place of the different antimalarial chemoprophylactic agents in the treatment of TSS was reviewed. Finally, the question of the appropriate duration of therapy for TSS was entertained. PMID- 1637746 TI - Pericardial effusion associated with minoxidil therapy: case reports. AB - Symptomatic pericardial effusion (PE) occurred in two of our patients with chronic renal failure (CRF) who had taken minoxidil for control of their hypertension. One of them died from the effects of cardiogenic shock due to cardiac tamponade. The 2 patients had taken minoxidil for over 3 months. Other patients who had CRF had not developed symptomatic PE while being treated with other anti-hypertensive agents. Our experience conforms with reports from elsewhere that minoxidil may cause PE. Therefore, patients with CRF who need minoxidil as an anti-hypertensive agent should be examined regularly for clinical evidence of PE. PMID- 1637747 TI - Tek FRODO: a new version of FRODO for Tektronix graphics stations. AB - A new version of the molecular graphics program FRODO was developed to allow the range of Tektronix graphics stations to be used for molecular modeling and crystallographic applications. The work was divided into two parts: first, the universal molecular modeling graphic package (Tek_MMGP) was written to enable basic modeling operations for Tektronix stations. Second, all routines of FRODO involving computer graphics were modified to fit the new hardware environment, and linked with Tek_MMGP. The resulting package, Tek_FRODO, has been used successfully for crystallographic refinement in several projects. The program, written in FORTRAN, is ready to be ported to any of Tektronix 3D graphics stations; it is available from the authors on request. PMID- 1637748 TI - Protein structure prediction from predicted residue properties utilizing a digital encoding algorithm. AB - Although many disparate methods have been applied to the problem, the accuracy of protein structural prediction still remains disappointingly low, averaging about 65% correct secondary structure assignment. A novel predictive method is presented here, which attempts to address some of the shortfalls inherent in representing a protein as a simple text-like sequence of amino acids, by deriving pattern-matching data from the predicted physical properties of a protein chain rather than from the sequence itself. A unique binary encoding algorithm is used to enable the property profiles to be correlated with known secondary structure, and hence to predict secondary structures for proteins with unknown structures. By treating the sequence in this manner, predictive accuracies averaging over 75% have been achieved. PMID- 1637749 TI - A molecular model for the retinol binding protein-transthyretin complex. AB - A three-dimensional model for the complex between human serum retinol binding protein and transthyretin (formerly named prealbumin) is presented. The model was obtained by interactive rigid-body computer graphics docking and the characterization of the molecular surfaces in terms of fractal dimension. Available experimental data, as well as results from molecular dynamics calculations, support the proposed model. PMID- 1637750 TI - PROBIT: a statistical approach to modeling proteins from partial coordinate data using substructure libraries. AB - A program (PROBIT) has been developed that allows the reconstruction of a complete set of three-dimensional protein coordinates from alpha-carbon coordinates. The program generates a statistical measure of polypeptide conformational behavior for substructures in a defined structural context from a library of highly refined protein structures. These statistics provide a prescription for substructure substitution from the database to allow regeneration of the complete protein structure. PMID- 1637751 TI - Automated site-directed drug design using molecular lattices. AB - Receptor-based drug design is predicated on the knowledge of the structure of a target receptor and the principles of molecule recognition. The objective is to produce a wide diversity of structures that are sterically and electrostatically complementary to a specified receptor site. Many drug-receptor interactions are controlled by a few key receptor groups. This observation leads to a design approach in which one focuses on chemical fragments that putatively interact with the key receptor groups. There then remains the difficult task of joining the fragments into molecular structures that match the spatial patterns of recognition forces in the receptor site. In this paper, we describe a new modeling program, BUILDER, that combines database searching techniques and structure generation algorithms within an interactive graphics modeling environment (MidasPlus). A novel tool for process communication (delegate) is introduced and examples of its use are given. To demonstrate the functionality of the package and its ability to produce novel structures, we examine the active site of HIV-1 protease. PMID- 1637752 TI - Computer graphics presentations and analysis of hydrogen bonds from molecular dynamics simulation. AB - To obtain better insights into the dynamic nature of hydrogen bonding, computer graphics representations were introduced as an aid for the analysis of molecular dynamics trajectories. A schematic representation of hydrogen bonding patterns is generated to reflect the frequency and the type of hydrogen bonding occurring during the simulation period. Various trajectory plots for monitoring geometrical parameters and for analyzing three-center hydrogen bonding were also generated. The methods proposed are applicable to a variety of biopolymers. In this study, hydrogen bonding in the d(G)6.d(C)6 system was examined. For the nucleic acid fragments examined, three-center hydrogen bonds can be classified as in-plane and major or minor groove types. The in-plane three-center hydrogen bond represents a stable state in which both bonds simultaneously satisfy the relaxed hydrogen bonding criteria for a measurable period. On the other hand, groove three-center hydrogen bonds behave as a transient intermediate state in a flip-flop hydrogen bonding system. PMID- 1637753 TI - Representation of noncovalent interactions in protein structures. AB - The energetics of solvent-atom and atom-atom nonbonded interactions can be described, for protein structures, in terms of the accessible and the contact atomic surface areas, respectively. This type of description emphasizes the importance of the local environment around groups in the three-dimensional structure of protein molecules. The graphical representation of nonbonded interactions according to this description allows one to visualize the spatial extent and distribution of these interactions and the relative stability of atoms or atomic groups in known or modified protein conformations. Applications of this short range description and of its graphical representation will be discussed. PMID- 1637754 TI - The House of Commons Health Committee Report on the Maternity Services. A personal view. PMID- 1637755 TI - Non-invasive first trimester antenatal diagnosis. PMID- 1637756 TI - Amnioinfusion: a question of benefits and risks. PMID- 1637757 TI - Is obstetric and neonatal outcome worse in fetuses who fail to reach their own growth potential? AB - OBJECTIVES: To determine the perinatal outcome of fetuses who had birthweights less than that expected from early third trimester ultrasound scanning. DESIGN: Retrospective estimation of centile fetal weight at early third trimester ultrasound scanning compared with actual centile birthweight corrected for gestational age, parity and sex. SETTING: Teaching Hospital Obstetric Unit, London. SUBJECTS: 197 unselected women with singleton cephalic pregnancies who were delivered at term in our unit between October 1989 and May 1990. MAIN OUTCOME MEASURES: CTG abnormality, need for fetal blood sampling in labour, meconium-staining of the amniotic fluid, mode of delivery, Apgar scores at 1 and 5 min, need for transfer of baby to neonatal unit, and need for neonatal intubation of the neonate at delivery. RESULTS: An actual birthweight greater than 5% less than the birthweight estimated from ultrasound scanning identified 44 babies (22%) with an increased risk of CTG abnormalities (chi 2 = 8.38, P less than 0.0025; Odds ratio (OR) = 2.54; 95% CI 1.36 to 4.78) and need for operative delivery (chi 2 = 5.81, P less than 0.0125; OR = 1.94; 95% CI 1.15 to 3.27), when compared with the remainder of the sample. Overall 14 (32%) of this group had birthweights above the 50th centile. A group of 44 babies selected as being the smallest for gestational age, without reference to growth pattern, had a similar excess morbidity. (All this group had birthweights below the 39th centile). CONCLUSIONS: This study supports the hypothesis that in-utero fetal growth pattern is as important for perinatal outcome as being small for gestational age per se. PMID- 1637758 TI - Sweeping of the membranes is an effective method of induction of labour in prolonged pregnancy: a report of a randomized trial. AB - OBJECTIVE: To determine whether sweeping of the membranes is an effective method of induction of labour in women with prolonged pregnancy. DESIGN: Randomized controlled trial. SETTING: A district maternity hospital. SUBJECTS: 65 women attending an antenatal clinic; 33 randomized to sweeping of the membranes and 32 to a control group. MAIN OUTCOME MEASURE: Proportion of women achieving spontaneous labour. RESULTS: Spontaneous labour occurred more often in the sweeping of the membranes group than in the control group (25/33 (76%) vs 12/32 (38%); odds ratio (OR) 4.65; 95% confidence interval (CI) 1.75 to 12.31; P = 0.002). In addition a greater proportion of women in the sweeping group had a cervical dilatation of 4 cm or more at the first vaginal examination in the labour ward (16/33 (49%) vs 5/32 (16%); OR 4.39; 95% CI 1.56 to 12.32; P = 0.005). There were fewer maternal infections in the sweeping group (0/33 vs 4/32 (12%); OR 0.12; 95% CI 0.02 to 0.88; P = 0.04). There were no differences in the type of analgesia used in labour, the mode of delivery or neonatal outcome. CONCLUSIONS: Sweeping of the membranes is an effective method of induction of labour in women with prolonged pregnancy. PMID- 1637759 TI - An economic evaluation of daycare in the management of hypertension in pregnancy. AB - OBJECTIVE: To evaluate the efficiency of daycare in the management of hypertension in pregnancy compared with inpatient management with prior domiciliary visits. DESIGN: Comparative study. SETTING: Two maternity teaching hospitals, Glasgow Royal Maternity Hospital which has an established daycare unit and Aberdeen Maternity Hospital with no daycare unit. MAIN OUTCOME MEASURES: Pregnancy outcomes in terms of maternal hypertensive complications, gestation at delivery, mode of delivery, birthweight, Apgar scores, admission rates and length of admission to special care baby unit. RESULTS: There was no significant difference in any of the measured pregnancy outcomes between the two hospitals. The average cost of treating a women with mild hypertension was 154.91 pounds in Glasgow and 136.59 pounds in Aberdeen. The average cost of treating women with a single episode of hypertension and women with a past history of hypertension was 88.65 pounds and 214.12 pounds in Glasgow and 31.18 pounds and 28.28 pounds in Aberdeen, respectively. If these two groups are excluded, the average cost of treating women with mild hypertension was 172.32 pounds in Glasgow and 201.13 pounds in Aberdeen. The majority of women were willing to attend daycare five times per week to avoid admission. CONCLUSION: Daycare management of hypertension in pregnancy is more efficient than inpatient care with prior domiciliary visits for most women, but less efficient for women with transient or previous hypertension. It is very acceptable to women. Domiciliary checking of women with hypertension found at outpatient clinics would reduce resource use. PMID- 1637760 TI - Fetal breathing movements in oligohydramnios are not increased by aminoinfusion. AB - OBJECTIVE: To determine whether fetal breathing movements (FBM) in pregnancies with oligohydramnios change with restoration of amniotic fluid volume. DESIGN: A prospective experimental study. SETTING: Fetal Medicine Unit, tertiary referral hospital. SUBJECTS: 16 women with singleton pregnancies complicated by severe oligohydramnios. INTERVENTIONS: Restoration of amniotic fluid volume by transabdominal amnioinfusion. Controls comprised pregnancies in which infused fluid leaked vaginally, so that oligohydramnios was not corrected. MAIN OUTCOME MEASURES: Change in total breathing movements, change in FBM incidence derived from 40 min recordings immediately before and after amnioinfusion. RESULTS: There was no significant difference in the change in total breathing movements or in the change in incidence of FBM between the 10 pregnancies in which amniotic fluid volume was restored, and the other six in which fluid leaked after infusion and volume was not restored. In both groups, there was no significant change with infusion in number of FBM (mean change -72, 95% CI -218 to +74 in the fluid retained group and -64, 95% CI -273 to +145 in the fluid-leaked group) and incidence of FBM (median change -2.5%, range -27 to +10 in the fluid retained group and -4.5%, range -34 to +15 in the fluid-leaked group). CONCLUSIONS: This study suggests that restitution of amniotic fluid volume in human pregnancies complicated by severe oligohydramnios does not acutely alter the incidence of FBM. These data support an increasing literature suggesting that impairment of fetal breathing is not the mechanism for oligohydramnios-related pulmonary hypoplasia. PMID- 1637762 TI - Sonographic estimation of fetal weight in diabetic pregnancy. AB - OBJECTIVE: To investigate whether fetal weight estimation by ultrasound in diabetic pregnancy might be based upon fetal abdominal circumference (AC) alone. DESIGN: A retrospective study. SETTING: Diabetes Center, Rigshospitalet and Ultrasound Laboratory, Glostrup Hospital, Copenhagen. SUBJECTS: Eighty-six diabetic pregnant women who had an ultrasound study within 2 days before delivery. RESULTS: We assessed in 73 fetuses various formulas based upon biparietal diameter and AC against formulas based upon AC alone, and these were only marginally less effective than the more complex ones. In 86 fetuses an AC was available. These fetuses were divided into a study population and a test population. The linear model was customized for the study population. Evaluation on the test population showed that the relative error (error as a percentage of birthweight) in predicting birthweight had a standard deviation of 7.8%. The efficacy of AC in detecting fetuses greater than 4000 g was examined in the test population: If AC greater than 36.0 cm was chosen as criterion for macrosomia the positive and negative predictive values were 80% (8/10) and 91% (30/33), respectively. CONCLUSION: Formulas for estimating fetal weight in diabetic pregnancy based on AC alone are almost as effective as more complex ones. We recommend a simple linear formula of fetal weight as a function of AC. PMID- 1637761 TI - Detection of small-for-gestational-age fetuses by ultrasound screening in a high risk population: a randomized controlled study. AB - OBJECTIVE: To assess the value of fetal weight estimation during routine third trimester ultrasound examinations for the identification of small-for-gestational age (SGA) fetuses, to promote active pregnancy management and so reduce perinatal morbidity. DESIGN: A prospective controlled randomized study. SETTING: Outpatient clinic at the Department of Obstetrics, Herlev University Hospital, Denmark. SUBJECTS: One thousand pregnant women considered at risk were selected consecutively from April 1985 to September 1987 and randomized to either a revealed-results group or a withheld-results group. INTERVENTION: All the women had an early ultrasound examination for estimation of gestational age. Both groups had routine ultrasound estimates of fetal weight after 28 weeks and then every third week until delivery. The results were available for clinical use only in the revealed group. MAIN OUTCOME MEASURES: Number of interventions during pregnancy (admission to hospital, elective delivery), emergency intervention during labour, and fetal outcome. RESULTS: Revealing the results of ultrasound estimates of fetal weight for gestational age during the third trimester resulted in statistically significantly increased diagnosis of SGA fetuses, of elective deliveries based on this diagnosis, and of healthy preterm babies admitted to the neonatal care unit, but no detectable overall improvement in weight for gestational age at birth, or in neonatal morbidity or mortality. CONCLUSION: This method of screening improved the diagnosis of SGA fetuses, but this was not followed by improved fetal outcome. PMID- 1637763 TI - Lung volume measured by functional residual capacity in infants following first trimester amniocentesis or chorion villus sampling. AB - OBJECTIVE: To determine the incidence of respiratory problems and lung volume abnormalities in babies born after first trimester amniocentesis or chorion villus sampling. DESIGN: A prospective randomized study. SETTING: Harris Birthright Research Centre for Fetal Medicine, Paediatric Respiratory Laboratory, King's College Hospital. SUBJECTS: Babies of mothers who had undergone first trimester amniocentesis (n = 74) or chorion villus sampling (CVS) (n = 86) for fetal karyotyping because of advanced maternal age, parental anxiety or family history of chromosomal abnormality in the absence of parental chromosome re arrangement. MAIN OUTCOMES: Respiratory distress in the neonatal period and lung volume as assessed by measurement of functional residual capacity (FRC). RESULTS: CVS was associated with a significantly higher incidence of neonatal respiratory distress, six infants in the CVS group but none in the amniocentesis group required admission to the special care baby unit because of respiratory distress (P less than 0.05). Although there was no significant difference in the mean FRC between the two groups (amniocentesis 29.7 ml/kg vs CVS 29.6 ml/kg) the overall incidence of FRC values less than 2.5th centile of the normal range was 9%. CONCLUSION: Both amniocentesis and CVS performed in the first trimester of pregnancy may impair antenatal lung growth. PMID- 1637764 TI - Fetal middle cerebral artery blood flow during normal active labour and in labour with variable decelerations. AB - OBJECTIVE: To assess the distribution of fetal blood flow impedance of the umbilical and middle cerebral artery in active uncomplicated labour and in labour complicated by variable decelerations. INTERVENTIONS: Blood flow impedance of the umbilical and fetal middle cerebral arteries was assessed by means of pulsed Doppler ultrasonography and measured by the resistance index (RI) and the systolic/diastolic ratio. SUBJECTS: 35 women at 38-40 weeks gestation admitted to, or monitored in the intrapartum unit. One group of 25 women had a normal active labour, the second group of 10 women were in active labour with moderate variable decelerations. A control group of 25 women--healthy pregnant women at term but not in active labour. All three groups were comparable for maternal age and parity. SETTING: Hospital department of obstetrics and gynaecology, Israel. DESIGN: A prospective descriptive study. RESULTS: There was a 40% reduction in middle cerebral artery blood flow impedance in the two groups of women in active labour compared with the control group. Umbilical blood flow did not differ significantly between the three groups. Fetal middle cerebral blood flow impedance in labour was not significantly different in uncomplicated labours and those complicated by fetal heart rate decelerations. CONCLUSIONS: During active labour, mechanisms that may be unrelated to low fetal blood oxygen content reduce fetal brain blood vessel impedance. PMID- 1637765 TI - Endometrial phospholipases A2, polycystic ovaries and pelvic pain. AB - OBJECTIVE: To compare the activity of calcium independent phospholipase A2 in the endometrium of women with polycystic ovaries and in women with normal ovaries, and to investigate the influence of chronic pelvic pain on phospholipase A2 activity. DESIGN: A prospective descriptive study. SETTING: The Samaritan Hospital for Women and the Unit of Metabolic Medicine, St Mary's Hospital Medical School, London. SUBJECTS: 73 women attending the Samaritan Hospital for Women for clip sterilization, infertility, early recurrent miscarriage or pelvic venous congestion. 45 of these women had no pelvic pain, 22 had normal ovaries and 23 had polycystic ovaries diagnosed by ultrasound. The other 28 women had chronic pelvic pain, 14 of them had normal ovaries and 14 polycystic ovaries. INTERVENTIONS: Endometrial tissue was obtained at curettage or from the excised uterus in the proliferative or secretory phase of the menstrual cycle. The activities of calcium dependent (type 1) and calcium independent (type 2) phospholipase A2 isoenzymes were measured in all endometrial samples. RESULTS: In all the women phospholipase A2 type 1 activity, was significantly higher in the secretory phase than in the proliferative phase (P less than 0.001). There was no difference between women with normal ovaries and those with polycystic ovaries at either stage of the cycle irrespective of whether or not chronic pelvic venous congestion was present. In women with normal ovaries, both with and without chronic pelvic pain, phospholipase A2 type 2 activity was significantly higher in the secretory phase than in the proliferative phase (P less than 0.02 and P less than 0.05 respectively) but in women with polycystic ovaries, with and without chronic pelvic pain, there was no significant difference in activity between the two phases of the cycle. Women with polycystic ovaries had markedly higher proliferative phase type 2 activity than women with normal ovaries (P less than 0.001). Secretory phase type 2 activity was similar in all the women investigated. CONCLUSION: These data suggest that phospholipase A2 type 2 activity is increased in proliferative phase endometrium of women with polycystic ovaries but that the increase is not associated with chronic pelvic venous congestion. PMID- 1637766 TI - Is transcutaneous electrical nerve stimulation of any value during cervical laser treatment? AB - OBJECTIVE: To assess the value of transcutaneous electrical nerve stimulation (TENS) during cervical laser therapy. DESIGN: Randomized three arm controlled clinical trial comparing (i) TENS, (ii) local anaesthetic and (iii) TENS plus local anaesthetic (direct infiltration of 2% lignocaine and 0.03 iu/ml octopressin). SETTING: Colposcopy Unit adapted to run randomized trials. SUBJECTS: 100 women with CIN and no previous experience of cervical surgery. MAIN OUTCOME MEASURE: Visual linear analogue pain scores. RESULTS: The median pain score associated with TENS was greater than the score associated with local anaesthesia (23% compared with 17%; P = 0.1). Combining TENS with local anaesthesia did not further reduce pain scores. CONCLUSION: Although there was considerable consumer satisfaction with TENS it provided no additional pain relieving effect in addition to direct infiltration of lignocaine and it is inferior to lignocaine alone. We are unable to advocate the use of TENS for laser treatment of the cervix. PMID- 1637767 TI - The cytological detection of persistent cervical intraepithelial neoplasia after local ablative treatment: a comparison of sampling devices. AB - OBJECTIVE: To determine whether the cytological detection of persistent cervical intraepithelial neoplasia (CIN) after local ablative treatment is improved by the use of sampling devices other than the Ayre's spatula. DESIGN: A randomized controlled study. SETTING: Lothian Area Colposcopy Clinic. SUBJECTS: 856 patients who had received local therapy (CO2 laser or cold coagulation) for CIN II or III between 9 and 30 months earlier. INTERVENTION: Each patient had three consecutive cervical smears taken, one with the Ayre's spatula, one with either the Aylesbury, the Rocket or the Multispatula device, and finally one with the Cytobrush. The allocation of which spatula and the order of the first two was randomized. Each patient had a colposcopic examination immediately after the smears were taken. MAIN OUTCOME MEASURES: A comparison of the detection of histologically proven persistent CIN by the Ayre's spatula with the detection of persistent disease by alternative sampling devices. RESULTS: Of the 856 patients 130 had histologically proven persistent CIN. Another 98 had suspicious findings on colposcopy but punch biopsies reported as histologically normal. Of the remaining patients with normal colposcopy 130 were randomly selected to form a control group. The cervical smears from these 358 women were reported. Significantly fewer Ayre's samples contained endocervical cells than Aylesbury samples (47% vs 59%, difference 12%; 95% CI 3%-21%; P less than 0.001), Rocket samples (47% vs 67%; difference 20%, 95% CI; 12%-32%; P less than 0.001) or Multispatula samples (47% vs 76%; difference 29%, 95% CI 19-38%; P less than 0.001). When punch biopsies contained CIN, dyskaryotic cells were seen in 10% of Ayre's samples, 4.3% of Aylesbury samples, 8.3% of Rocket samples, and in no smear taken with the Multispatula. Obtaining a third smear with the Cytobrush did not substantially improve the detection rate of dyskaryosis. Neither the order of use of the spatulas, the form of initial treatment nor the size of the transformation zone had any apparent effect on the cytological detection of persistent CIN. CONCLUSIONS: We recommend that surveillance of patients who have received local ablative therapy for CIN should be by both cytology and colposcopy, and that cytological samples should be obtained using the Ayre's spatula. PMID- 1637768 TI - Erythrocyte membrane composition in pregnancy-induced hypertension: evidence for an altered lipid profile. AB - OBJECTIVE: To investigate whether the increased membrane fluidity postulated as a possible contributing factor to the hypertensive states of pregnancy is related to the lipid composition of the erythrocyte membrane. DESIGN: An observational case control study. SUBJECTS: 30 women with pregnancy induced hypertension, 26 normotensive pregnant women matched for gestational age, and 10 normotensive non pregnant nulliparous women. INTERVENTIONS: Erythrocyte membranes were prepared from venous blood samples obtained from all the women. MAIN OUTCOMES MEASURES: Lipid analysis, including cholesterol to phospholipids ratio, distribution of phospholipid classes and fatty acid composition of total phospholipids in erythrocyte ghosts. RESULTS: The cholesterol/phospholipid ratio was significantly higher in the women with pregnancy induced hypertension compared with the normotensive pregnant women (mean 1.24, SD 0.31, 95% CI 1.12 to 1.35 vs mean 0.90, SD 0.09, 95% CI 0.86 to 0.94; P less than 0.01). Normotensive non-pregnant erythrocyte membrane cholesterol/phospholipid ratio was 0.88 (SD 0.11, 95% CI 0.79 to 0.96). The percentage distribution of different phospholipid classes and fatty acid composition was similar in all the four groups. CONCLUSIONS: The increased cholesterol/phospholipid ratio of the erythrocyte membrane found in pregnancy-induced hypertension represents one factor involved in the pathophysiology of this condition and a possible biochemical marker of the disease. PMID- 1637770 TI - Cord insulin and C-peptide--distribution in an unselected population. AB - OBJECTIVE: To assess the distribution of cord blood insulin in an unselected population, and examine its relation to birthweight centiles. SETTING: District General Hospital in Nottinghamshire. SUBJECTS: 209 unselected singleton births. MEAN OUTCOME MEASURE: Cord blood insulin; cord blood C-peptide; birthweight centiles. RESULTS: Hyperinsulinaemic babies (greater than 97th centile for cord insulin) were found at all birthweight centiles. 15% of high birthweight babies were hyperinsulinaemic. For low birthweight babies, the distribution of cord insulin/C-peptide was skewed indicating a high number of low values. Hypoinsulinaemic babies were present up to the 50th centile for birthweight. CONCLUSIONS: Abnormalities of fetal insulinisation may be found in babies of all birthweights. PMID- 1637769 TI - Detection of fetal DNA in trans-cervical swabs from first trimester pregnancies by gene amplification: a new route to prenatal diagnosis? AB - OBJECTIVE: To determine whether fetal sex can be predicted from fetal DNA retrieved transcervically from the lower part of the uterine cavity in the first trimester of pregnancy. DESIGN: Prospective observational study. SETTING: St James's University Hospital, Leeds. SUBJECTS: 33 women undergoing legal termination of pregnancy at 9 to 13 weeks gestational age. INTERVENTIONS: Before termination of pregnancy samples for DNA analysis were obtained with cotton wool swabs from the vagina, cervix and transcervically in 26 women. In the other seven women samples were obtained using a transcervical cell retrieval (TraCeR) procedure involving flushing the lower uterine cavity with 5 ml saline. MAIN OUTCOME MEASURES: Detection of Y-chromosome specific DNA sequences by the polymerase chain reaction (PCR) in cotton wool swabs taken from the lower uterus in the first trimester of pregnancy to predict fetal sex in comparison with standard cytogenetic analysis. Histological and immunohistochemical analysis of samples obtained by flushing of the lower uterine cavity (TraCeR) to confirm the presence of trophoblast. RESULTS: Fetal sex was predicted accurately in 25 of the 26 pregnancies investigated. Immunohistochemical analysis identified syncytial trophoblast fragments in all seven pregnancies investigated by TraCeR. CONCLUSION: Trophoblast may be retrieved from the lower uterus in the first trimester by swabs or TraCeR. When purification of these syncytial fragments can be achieved using immuno-magnetic technology, this test will enable prenatal diagnosis of single gene defects in the fetus by the polymerase chain reaction. PMID- 1637771 TI - Spinal muscular atrophy and pregnancy. PMID- 1637773 TI - Polycystic ovaries in association with mullerian duct anomalies. PMID- 1637772 TI - Vaginal ultrasound in donor insemination. PMID- 1637774 TI - Laparoscopic tubal manipulating forceps for extrusion of early ectopic pregnancy. PMID- 1637775 TI - The prevalence, aetiology and clinical significance of pseudosinusoidal fetal heart rate patterns in labour. PMID- 1637776 TI - Emergency cervical cerclage. PMID- 1637777 TI - Is stage I epithelial ovarian cancer overtreated both surgically and systemically? Results of a five-year cancer registry review. PMID- 1637778 TI - Fetal heart block associated with anti-Ro(SS-A) antibody--current management. A review. PMID- 1637779 TI - Characterization of lymphocytes infiltrating human breast cancer: specific immune reactivity detected by measuring cytokine secretion. AB - Primary breast cancers from 19 patients and draining lymph nodes from nine of them (seven containing metastatic tumor) were used in growing tumor-infiltrating lymphocytes (TIL) in culture. TIL were studied for proliferation, phenotype, cytotoxicity, and the ability to secrete cytokines in response to autologous tumor. Lymphocytes from primary breast tumors proliferated in 15 of 19 cultures, a median of 6.7 x 10(3)-fold in 65 days. For eight of nine patients, lymphocytes derived from draining lymph nodes proliferated in culture, a median of 110-fold in 49 days. Breast TIL became predominantly CD4+ cells over time in culture and were 73% CD4+ and 21% CD8+ (means) at 63 days (median). Lymph node lymphocytes were 63% CD4+ at 51 days. TIL were poorly lytic in 4-hour 51Cr release assays. Lysis of autologous tumor occurred in only one of 12 breast TIL and one of nine lymph node cultures. This lysis was low (15% at effector:target = 40:1) and was nonspecific (non-major-histocompatibility-complex restricted). Cytokine secretion was tested by co-culturing TIL with autologous or allogeneic tumors for 24 hours. Cytokines were measured in culture supernatants by enzyme-linked immunosorbent assay or radioimmunoassay. TIL from three of 11 patients specifically secreted granulocyte macrophage-colony-stimulating factor, tumor necrosis factor-alpha and interferon-gamma when stimulated by autologous tumor and not by a panel of four to five allogeneic breast cancers. Cytokine secretion has made possible the identification of lymphocytes infiltrating breast cancers with specific immune reactivity. This finding will guide the development of new immunotherapies for patients with breast cancer. PMID- 1637780 TI - Inhibitory effects of cytokines on vascular endothelial cells: synergistic interactions among interferon-gamma, tumor necrosis factor-alpha, and interleukin 1. AB - The formation of new blood vessels is critical to tumor growth and metastasis and since endothelial cells are the principal cell type comprising such blood vessels, we carried out experiments to test whether the growth of endothelial cells in vitro can be inhibited by low doses of combinations of cytokines. We show that growth of mouse aortic endothelial cells can be inhibited in vitro by combinations of cytokines that, administered singly even at ten times higher concentrations, have only marginal effects. In particular, interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma), acting synergistically at low, subthreshold concentrations, are able to completely inhibit the growth of endothelial cells in vitro. PMID- 1637781 TI - Depot characteristics and biodistribution of interleukin-2 liposomes: importance of route of administration. AB - Due to rapid clearance of interleukin-2 (IL-2), it has had limited effective use as an in vivo immunostimulant. Current experimental and clinical protocols generally must utilize large doses, multiple injections, or continuous infusions of IL-2 in order to achieve significant immunostimulation, often at the expense of systemic toxicity. Therefore, the pharmacodynamics of IL-2 liposomes were investigated. IL-2 liposome incorporation efficiency was 80.4% (SD 5.5); vesicle diameter was 1.65 microns (SD 0.09) as determined by fluorescence-activated cell sorting (FACS). Both formulation (free cytokine vs. IL-2 liposomes) and route of administration were important variables in determination of the biodistribution and pharmacokinetic characteristics of IL-2. When free [125I]IL-2 was given i.v. to mice, only 6.5% was in the blood and 3% in liver and spleen 2 h after injection; on the other hand, at 2 h greater than 70% of i.v. [125I]IL-2 liposomes were detected in the blood, liver, spleen, and lungs. Mean i.v. elimination t1/2 from the blood of rats given 20 x 10(6) U/kg free cytokine or IL 2 liposomes was 41 versus 102 min, respectively, as measured by bioassay and 59 and 119 min as measured by enzyme immunoassay (EIA). After i.v. administration, the estimated Vd of IL-2 liposomes was 13-fold smaller than the free cytokine. Intrathoracic (i.tx.), i.p., and s.c. administration of [125I]IL-2 to mice also demonstrated significant depot effects when IL-2 was incorporated into liposomes. These data suggest IL-2 liposomes may provide in vivo immunostimulation superior to the free cytokine due to biodistribution and depot characteristics. PMID- 1637782 TI - Phase I trial of recombinant macrophage colony-stimulating factor by rapid intravenous infusion in patients with cancer. AB - Fourteen patients were entered into a phase I dose-escalation trial of macrophage colony-stimulating factor (M-CSF). M-CSF was administered to inpatients by rapid 15 min i.v. infusion every 8 h x 5 days, repeated after a 9-day rest. Dose levels evaluated were 20, 40, 80, 330, and 1,100 micrograms/m2. Monitoring of patients every 4 h included vital signs, daily complete blood count (CBC), and serum chemistries (SGOT, creatinine, and bilirubin) while receiving M-CSF. No clinical or laboratory evidence of toxicity was seen. The average serum t1/2 varied with dose level. At 330 and 1,100 micrograms/m2, the serum t1/2 was 25 and 84 min, respectively, implying a saturable mechanism of clearance. After 5 days of treatment, the t1/2 decreased by twofold, consistent with enhancement of the saturable mechanism. Monocyte cytotoxicity against the A375 melanoma cell line was evaluated pretreatment and day 5 of each cycle. No consistent enhancement of monocyte cytotoxicity was seen. No effect on peripheral blood monocyte number was seen until the 1,100 micrograms/m2 dose level. At this dose level, the mean monocyte number on day 5 was increased compared to baseline (1,300 mm3 vs. 300/mm3). Clinical activity was seen in two patients with previously progressive leiomyosarcoma metastatic to the liver. A partial response (PR) lasting 7 months occurred at the 330 micrograms/m2 dose level while a patient treated at 1,100 micrograms/m2 has had stable disease for 20+ months. The maximum tolerated dose (MTD) of M-CSF was not determined. Based on clinical responses, a phase II trial is warranted in patients with metastatic soft tissue sarcoma. PMID- 1637783 TI - Interferon-gamma induced by administration of recombinant interleukin-2 to patients with cancer: kinetics, dose dependence, and correlation with physiological and therapeutic response. AB - The administration of recombinant interleukin-2 as an i.v. bolus at dose levels of from 1 to 30 MIU/m2 to patients with cancer induces easily measurable serum interferon-gamma levels of 1 to 500 U/ml. After a lag of 1 h, interferon-gamma rises to a maximum at 4 h and then slowly decreases. The peak values are poorly correlated with the dose of interleukin-2, and thus must be also be dependent on other factors. Successive administration of interleukin-2 typically increases the peak level of interferon-gamma fourfold, but does not diminish the lag period. Peak levels of interferon-gamma are also increased by concurrent administration of interferon-beta with interleukin-2. Continuous i.v. infusion of 1.5 to 20 MIU/m2 of interleukin-2/day results in interferon-gamma levels of 1 to 7 U/ml. Hypotension, which is characteristically associated with interleukin-2 administration, is correlated with interferon-gamma levels in only some patients. There was no apparent correlation between tumor regression and serum interferon gamma levels. PMID- 1637784 TI - Human leukocyte antigen expression in renal cell carcinoma lesions does not predict the response to interferon therapy. AB - Human leukocyte antigen (HLA) classes I and II molecules are essential for antigen presentation to cytotoxic T cells and helper T cells, respectively. Consequently, they may play a role in anticancer immunotherapy as well. We studied whether the pretreatment HLA phenotype of the tumor is predictive for response to interferon immunotherapy in vivo. Therefore, renal cell carcinoma (RCC) primary tumor lesions from 31 patients treated with interferon-alpha and interferon-gamma (13 responders and 18 nonresponders) were analyzed retrospectively for HLA antigen expression with immunohistochemical methods. Furthermore, from eight patients, pretreatment metastatic lesions were examined. In the primary tumors HLA class I expression was high: in 26 of 30 lesions more than 50% cells were stained. HLA class II expression was mostly low: in 14 of 31 primary tumors less than 5% cells were stained. A significant correlation was found between HLA phenotype of primary tumors and corresponding metastases. There was no association between tumor HLA classes I and II antigen expression and clinical response to interferon therapy. In conclusion, pretreatment HLA phenotype of RCC has no predictive value for outcome of interferon immunotherapy. A role for treatment-induced changes in HLA expression in vivo, however, can not be excluded. These findings do not provide indications for the working mechanism of interferon immunotherapy in vivo. PMID- 1637785 TI - Selective factor Xa inhibition by recombinant antistasin prevents vascular graft thrombosis in baboons. AB - A baboon model of high-shear, platelet-dependent vascular graft thrombosis was used to assess the antithrombotic effect of recombinant antistasin (rATS), a 119 amino acid protein with selective, subnanomolar inhibitory potency against coagulation factor Xa. In this model, a Dacron vascular graft segment of a femoral arteriovenous (AV) shunt provided the thrombogenic stimulus. Antithrombotic efficacy of rATS was assessed by continuous monitoring of 111In labeled platelet and 125I-labeled fibrin(ogen) deposition onto the graft surface and blood flow through the vascular shunt. Systemic intravenous administration of rATS (2 or 4 micrograms/kg.min-1) dose dependently decreased both platelet and fibrin(ogen) deposition onto the graft. Vascular graft thrombus formation was completely inhibited at a systemic dose of rATS of 4 micrograms/kg.min-1. None of the AV shunts in animals receiving rATS at either dose occluded, and blood flow was maintained at 81 +/- 4% (2 micrograms/kg.min-1 rATS) or 96 +/- 3% (4 micrograms/kg.min-1 rATS) of basal flow. Systemic fibrinopeptide A elevations in response to exposure to the Dacron graft segment were completely suppressed by both doses of rATS. The ex vivo activated partial thromboplastin times were extended to greater than 150 seconds during infusion of both doses of rATS; however, even at fully antithrombotic doses, template bleeding times were not significantly increased. Thus, in this baboon model, rATS is a potent antithrombotic agent that inhibits both platelet and fibrin(ogen) deposition onto a Dacron vascular graft segment. Furthermore, these results demonstrate that selective inhibition of coagulation factor Xa by rATS can completely prevent vascular graft thrombus formation without significantly compromising primary hemostasis as measured by template bleeding time. PMID- 1637786 TI - Turnover of synthetic class A amphipathic peptide analogues of exchangeable apolipoproteins in rats. Correlation with physical properties. AB - Peptide analogues of the class A amphipathic helixes from exchangeable apolipoproteins mimic apolipoprotein (apo) A-I in a number of ways, including the ability to activate the enzyme lecithin:cholesterol acyltransferase, to associate with high density lipoproteins (HDLs), and to form HDL-like particles in the presence of lipids. This study investigated the metabolic properties of several of these peptide analogues in the rat. Peptide analogues studied were 18A (referred to as L-18A to differentiate it from D-18A, and which mimics apolipoprotein amphipathic helical domains in its charge distribution), 37pA (a dimer of two 18A monomers separated by a proline), 18R (with reversed charge distribution compared with 18A), and D-18A (identical in amino acid sequence to 18A but synthesized from D-amino acids). Peptides were radiolabeled with 125I. In addition, metabolism of rat and human 125I-apo A-I and human 14C-apo A-I was studied; no significant differences in clearance of these preparations were seen. Clearance data were fitted to multiexponential equations to give half-times of clearance; biexponential equations consistently provided the best nonlinear least squares curve fit. The order of relative lipid affinity determined in vitro was 37pA greater than apo A-I greater than D-18A = L-18A greater than 18R. Half-times of clearance were in the same approximate rank order: 37pA, 6.9 +/- 3.3 hours (mean +/- SD); apo A-I, 6.9 +/- 1.8 hours; D-18A, 4.0 +/- 1.0 hours; L-18A, 4.6 +/- 1.6 hours; and 18R, 0.9 +/- 0.1 hour.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637787 TI - Significant association between low-molecular-weight apolipoprotein(a) isoforms and intermittent claudication. AB - The role of lipoprotein(a) (Lp[a]) and apolipoprotein(a) (apo[a]) isoforms in symptomatic peripheral atherosclerosis was studied in 100 randomly selected middle-aged (45-69 years) men with intermittent claudication (IC) and 100 randomly selected healthy control (C) subjects. IC and C subjects were matched pairwise for sex, age, and smoking habits. Plasma Lp(a) concentrations were significantly higher in IC subjects, with a median value of 20.12 mg/dl, compared with 11.11 mg/dl in C subjects (p less than 0.0009). The elevated Lp(a) concentration was to a great extent due to a significant difference in the frequency distribution of apo(a) isoforms between IC and C subjects (p less than 0.029). Low-molecular-weight apo(a) isoforms were more prevalent in IC than C subjects. Also, IC subjects with apo(a) S2 and S3 phenotypes had higher Lp(a) concentrations than control subjects with the same phenotypes: S2:60.70 mg/dl (IC) and 48.69 mg/dl (C), p less than 0.038; and S3: 30.18 mg/dl (IC) and 12.01 mg/dl (C), p less than 0.042, so other still-unknown factors, genetic or nongenetic, may be important. Stepwise logistic regression analysis demonstrated that Lp(a) concentration contributed significantly (p less than 0.0002) to IC, independent of age, smoking, hypertension, diabetes mellitus, plasma total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, apo B, and plasma total triglycerides. Apo(a) isoforms grouped according to molecular weight were also independent of the above risk factors associated (p = 0.016) with the occurrence of IC because of their low-molecular weight but were not independent of Lp(a) concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637788 TI - Dietary fish oil plus lovastatin decreases both VLDL and LDL apo B production in miniature pigs. AB - Our previous apolipoprotein (apo) B kinetic studies of miniature pigs fed fish oil (Maxepa) demonstrated that very low density lipoprotein (VLDL) apo B concentrations were markedly reduced but that low density lipoprotein (LDL) concentrations were only modestly lowered because of a threefold increase in the conversion of VLDL apo B to LDL. In the present study, the effect of Maxepa plus lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on apo B metabolism was assessed. Miniature pigs (n = 6) were simultaneously injected with autologous 131I-VLDL and 125I-LDL after a diet of pig chow supplemented with 30 g/day of Maxepa and again after the addition of lovastatin, 30 mg/day. Kinetic data were analyzed by compartmental analysis with use of the CONSAM program. Compared with Maxepa alone, the addition of lovastatin reduced VLDL apo B concentrations by 21% (p less than 0.003) because of reduced VLDL apo B production (26%, p less than 0.005), as the fractional clearance rate was not affected. Conversion of VLDL apo B to LDL was reduced by 48% (p less than 0.005), and the direct removal of VLDL apo B from plasma was reduced by 25% (p less than 0.01). Maxepa plus lovastatin reduced LDL apo B concentrations by 44% (p less than 0.004). This was due to a 38% (p less than 0.002) decrease in LDL production, which was primarily derived from VLDL. The LDL apo B fractional catabolic rate was not significantly changed. Thus, a combination of Maxepa and lovastatin reduces both VLDL and LDL apo B concentrations, primarily by decreasing production rates. PMID- 1637789 TI - Abnormalities of VLDL, IDL, and LDL characterize insulin-dependent diabetes mellitus. AB - To identify abnormalities of serum lipoprotein composition and concentration that were specific to insulin-dependent diabetes mellitus (IDDM), the procedure of discontinuous gradient ultracentrifugation was employed to isolate lipoprotein fractions in 44 patients with IDDM, 24 nondiabetic subjects with similar lipid and lipoprotein concentrations, and 19 healthy normocholesterolemic (less than 5.2 mmol/l [less than 200 mg/dl]) subjects. The mass concentration of low density lipoprotein (LDL) was greater in IDDM than in both control groups. The free cholesterol to phospholipid ratio in large very low density lipoprotein (VLDL) was greatest in IDDM in comparison with both of the other groups. The contribution of triglyceride to total large VLDL mass was greater, whereas that of phospholipids was lower, in IDDM than in the dyslipidemic nondiabetic group. Protein concentration was reduced and phospholipid increased in small VLDL in IDDM in comparison with both control groups, and the contribution from protein to lipoprotein mass was least in IDDM. Similarly in intermediate density lipoprotein (IDL), the protein concentration and its contribution to overall mass was also lower in IDDM than in either control group, but by contrast, the phospholipid content was increased. The cholesteryl ester to protein ratio was highest in both small VLDL and IDL in IDDM in comparison with both control groups, whereas the free cholesterol to phospholipid ratio in IDL was least in IDDM. In LDL, total cholesterol and triglyceride concentrations were greatest and the contribution from protein to lipoprotein mass was least in IDDM in comparison with both control groups. The LDL free cholesterol to phospholipid ratio was greater in IDDM than in dyslipidemic control subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637790 TI - Oxidatively modified HDLs are potent inhibitors of cholesterol biosynthesis in human skin fibroblasts. AB - Several biological properties of lipoproteins are modified by oxidative reactions. Modified lipoproteins are rapidly degraded by macrophages, and this is likely to be a major pathway for the formation of foam cells in the early phases of atherosclerosis. The effect of modification on other aspects of cholesterol homeostasis has, however, received lesser attention. In this study, the influence of copper ion- as well as rat aortic smooth muscle cell-oxidation-modified high density lipoprotein (HDL) on cholesterol biosynthesis in human skin fibroblasts has been investigated. Modified lipoproteins eluted at higher ionic strength than did control HDL on a Mono-Q 5/5 anion-exchange column. However, only copper ion modified HDLs displayed greater electrophoretic mobility than did control lipoproteins on agarose gel electrophoresis. Both control and modified HDLs decreased cholesterol esterification in fibroblasts. On the other hand, whereas control HDLs were virtually ineffective in modulating cholesterol biosynthesis, modified HDLs had a significant suppressing effect. This was observed in normal as well as low density lipoprotein (LDL) receptor-defective fibroblasts, which are unresponsive to the LDL-mediated downregulation of cholesterol synthesis. These results are consistent with the concept that oxidative modification of HDLs drastically alters their effect on cholesterol homeostasis in fibroblasts. The data furthermore suggest the existence of a lipoprotein pathway for cholesterol biosynthesis regulation that is independent of the LDL receptor-mediated pathway. Downregulation of cholesterol biosynthesis would be a new function for oxidatively modified lipoproteins. PMID- 1637791 TI - Endocytosis of oxidized LDL and reversibility of migration inhibition in macrophage-derived foam cells in vitro. A mechanism for atherosclerosis regression? AB - The ability of macrophage-derived foam cells to migrate from atherosclerotic lesions represents one potential mechanism for the regression of atherosclerosis. It is, however, generally recognized that the transformation of macrophages into foam cells results in greatly reduced migrational ability. In the present study, we set out to investigate the factors affecting migratory capability in foam cell like cells with the use of an in vitro assay. Foam cell-like cells were prepared by incubating macrophages in the presence of oxidized low density lipoprotein (LDL). The transformation to a typical foam cell morphology was demonstrated by Nile red staining (light microscopy), and the mechanisms of binding, uptake, and intracellular processing of oxidized LDL were established by colloidal gold labeling on the ultrastructural level. With the in vitro assay, the migration of these foam cell-like cells was found to be markedly inhibited compared with untreated, control macrophages. However, zymosan-activated mouse serum restored migration in oxidized LDL-treated cells to levels similar to those of control cells. Restoration of migratory capacity was accompanied by alterations in the cytoskeleton system, especially in actin arrangement. PMID- 1637792 TI - Smoking is a potential confounder of the Chlamydia pneumoniae-coronary artery disease association. AB - Two recent studies, which did not adequately control for smoking status, found associations between Chlamydia pneumoniae serological titers and various manifestations of coronary artery disease (CAD). The validity of C. pneumoniae CAD associations found in case-control studies has been criticized on the basis that smoking, known to be associated with CAD and hypothesized to be associated with C. pneumoniae seroreactivity via an increased prevalence of respiratory infection in smokers, could be an uncontrolled confounder in these studies. We investigated associations between current smoking status and C. pneumoniae serological titers in a cohort of 365 outpatients (mean age, 34 years) with respiratory illness. Current smokers were significantly (p = 0.04) more likely than nonsmokers to have C. pneumoniae titers greater than or equal to 1:128, and there was a significant (p less than 0.05) "dose-response" association between titer category and smoking, which persisted after controlling for age and sex in a logistic-regression model. These results support the hypothesis that smoking may be a confounder of the association of C. pneumoniae antibody titer and smoking-associated diseases such as CAD. Future studies into these associations should control for cigarette use. PMID- 1637793 TI - Antithrombotic effect of a monoclonal antibody against tissue factor in a rabbit model of platelet-mediated arterial thrombosis. AB - Activation of the coagulation system by contact of circulating blood with tissue factor, a component of the extrinsic blood coagulation pathway that is produced in the vessel wall, may represent a pathway for the initiation of thrombosis in atherosclerotic vessels. This hypothesis was tested in vivo in a rabbit femoral artery eversion (inside-out) graft model, in which the adventitia, with its tissue factor, was exposed to circulating blood. Intra-arterial infusion of a neutralizing monoclonal antibody against tissue factor (D3) at a rate of 12 mg/kg over 15 minutes prevented thrombosis of a 7-8-mm eversion graft within a 2-hour observation period in four of five rabbits, whereas with a control antibody infusion (MA-15C5), occlusion occurred within 2 hours in five of six rabbits. In vitro immersion before reinsertion of the arterial segment in a solution containing 2 mg/ml of the control antibody for 30 minutes was associated with occlusion in all six rabbits, whereas pretreatment with D3 was associated with persistent patency in three of nine rabbits. Stepwise logistic-regression analysis of the results with perfusion status as the dependent variable and type of antibody (D3 or MA-15C5), application method (infusion versus immersion), and graft segment length as independent variables yielded a significant difference in frequency of occlusion with the two antibodies (p = 0.016). It is concluded that exposure of tissue factor to flowing blood may constitute a trigger mechanism for platelet-mediated arterial thrombosis. PMID- 1637794 TI - Influence of gender, body mass index, and age on response of plasma lipids to dietary fat plus cholesterol. AB - We have conducted a crossover, randomized, double-blind dietary trial that tested the hypothesis that gender influences the response of plasma lipids, in particular high density lipoprotein (HDL) cholesterol, to dietary fat plus cholesterol. Twenty-six men and 25 women were matched for age, low density lipoprotein (LDL) cholesterol, triglyceride, and body mass index (BMI). After a 2 week baseline low-fat (27% of calories), low-cholesterol period, subjects were given two isocaloric liquid supplements for 3 weeks each, one containing 31 g fat (56% saturated) and 650 mg cholesterol, and the other fat free. The baseline HDL2 cholesterol level was significantly higher in women: 0.41 versus 0.26 mmol/l (p less than 0.01). Importantly, women also showed a greater rise in HDL2 cholesterol concentration with the fat/cholesterol supplement: 0.09 versus 0.03 mmol/l (p less than 0.01). The greater increment in women was related to their higher baseline HDL2 cholesterol levels. With the fat and cholesterol supplement, LDL cholesterol values rose from 3.76 to 4.04 mmol/l in women and from 3.77 to 4.13 mmol/l in men. The baseline LDL cholesterol value was found to account for about 35% of the variance in the rise in LDL cholesterol level with fat and cholesterol supplementation in both men and women less than 50 years. In men only, there was a significant effect of age: the change in LDL cholesterol with the fat/cholesterol supplement was 0.16 mmol/l in those less than 50 and 0.54 mmol/l in those greater than 50 years old (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637795 TI - Flow affects development of intimal hyperplasia after arterial injury in rats. AB - This study examined the effects of blood flow on intimal hyperplasia after balloon catheter injury of the rat common carotid artery. Flow was altered by ligation of the opposite common carotid artery (increased flow) or of the ipsilateral internal carotid artery (decreased flow). Blood flow decreased by 35% in the low-flow group and increased by 29% in the high-flow group. Similar changes in mean velocity were observed. Cross-sectional intimal area was significantly greater in the low- than the high-flow group at 2 weeks (0.11 +/- 0.01 versus 0.06 +/- 0.01 mm2, p less than 0.01) and 4 weeks (0.17 +/- 0.02 versus 0.12 +/- 0.01 mm2, p = 0.01) but not at 1 or 8 weeks. Smooth muscle cell proliferation rates (thymidine labeling indexes) were not different in high- and low-flow groups at 2 days and at 1 and 4 weeks. Matrix accumulation at 2 and 4 weeks was the same in both groups. Mature neointima did not respond to changes in flow; when vessel ligation was delayed until 2 months after injury, there was no effect on neointimal area. These data indicate that early neointimal hyperplasia is increased when flow is reduced, possibly because of alteration of smooth muscle cell migration. PMID- 1637796 TI - Normal postprandial lipemia in men with low plasma HDL concentrations. AB - To examine the relation between postprandial lipemia and high density lipoprotein (HDL) concentrations, we measured the plasma triglyceride and retinyl palmitate responses to 50-g fat meals of 1) 25 men with low HDL cholesterol concentrations (less than 36 mg.dl-1) and normal fasting triglyceride concentrations, 2) 25 men with normal HDL cholesterol (greater than 40 mg.dl-1) and normal fasting triglyceride concentrations, and 3) 20 men with mild to moderate fasting hypertriglyceridemia (250-347 mg.dl-1). The average magnitude of postprandial lipemia induced by the fat meals was markedly higher in the hypertriglyceridemic men (593 +/- 311 mg.dl-1.8 hr) than in either of the normolipidemic groups. In normotriglyceridemic men with low HDL cholesterol, mean postprandial lipemia (303 +/- 158 mg.dl-1.8 hr) was similar to the corresponding value of men with normal HDL (283 +/- 130 mg.dl-1.8 hr). Postprandial plasma retinyl palmitate concentrations, which reflect chylomicron remnant metabolism, also were similar in normal-HDL and low-HDL groups. These data suggest that defects in chylomicron triglyceride clearance that give rise to excess postprandial lipemia are not a common occurrence in normolipidemic men with low HDL cholesterol concentrations. Accordingly, the low HDL cholesterol concentrations measured in the normotriglyceridemic men in this study must be attributable to factors other than an exaggerated postprandial lipemia. PMID- 1637797 TI - Persistence of abnormalities in metabolism of apolipoproteins B-100 and A-I after weight reduction in patients with primary hypertriglyceridemia. AB - Obesity commonly accompanies hypertriglyceridemia, and weight reduction is widely recommended for treatment of elevated triglyceride levels. To determine whether weight reduction will normalize lipoprotein metabolism in overweight, hypertriglyceridemic patients, 10 such male patients underwent weight loss until their body weights were within the desirable range. After reestablishment of a steady state in body weight at the lower level, measurements were made of plasma lipid, lipoprotein, and apolipoprotein levels and the kinetics of low density lipoprotein (LDL) apolipoprotein B-100 (apo B) and apolipoprotein A-I (apo A-I). The patients lost an average of 10.6 +/- 2.1 kg (mean +/- SEM). Plasma triglyceride concentrations fell from 431 +/- 42 mg/dl to 248 +/- 27 mg/dl (p less than 0.001), whereas concentrations of total cholesterol, LDL cholesterol, total apo B, and high density lipoprotein (HDL) cholesterol were unchanged after weight loss. On average, the fractional catabolic rates (FCRs) for LDL were much higher in the patients after weight loss than in 16 normal control subjects (0.55 +/- 0.06 versus 0.31 +/- 0.06 pool/day), and input rates for LDL also were higher for hypertriglyceridemic patients after weight loss (22.2 +/- 2.4 versus 12.8 +/- 2.3 mg/kg.day). Compared with 20 normal control subjects, hypertriglyceridemic patients after weight reduction had persistent low HDL cholesterol levels (32 +/- 2 versus 54 +/- 3 mg/dl) as well as low apo A-I levels (99 +/- 5 versus 122 +/- 4 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637798 TI - Autoradiographic analysis of the distribution of 125I-tyramine-cellobiose-LDL in atherosclerotic lesions of the WHHL rabbit. AB - It is well established that plasma lipoproteins enter the artery wall and play a role in the atherogenic process. However, it is still unclear where within developing atherosclerotic lesions lipoproteins accumulate and which arterial cells participate in the metabolism of these lipoproteins. For this reason, light and electron microscopic autoradiograms were prepared from sections of lesioned aortas of Watanabe heritable hyperlipidemic (WHHL) rabbits 44 hours after injection of 125I-tyramine cellobiose-low density lipoprotein (TC-LDL). After uptake of 125I-TC-LDL and intracellular degradation of the LDL protein, the nondegradable TC ligand remains trapped and thus demarcates the cells participating in the degradation of LDL. Results of other studies indicate that 48 hours after injection into WHHL rabbits, about one half of the 125I label present in lesions represents accumulated degradation products while the remaining 125I label is present as intact 125I-TC-LDL. The distribution of autoradiographic silver grains was analyzed at low resolution in fatty streaks, transitional lesions, and advanced atheroma. In all cases, the majority of silver grains were associated with superficially located subendothelial macrophage derived foam cells. In more advanced lesions, labeling was predominant in foam cells situated within the lateral margins of the lesions. Morphometric quantification of the distribution of silver grains in electron photomicrographs of fatty streaks from two young WHHL rabbits strongly supported the data obtained at the light microscopic level. In early fatty streaks from the aortic arch and the thoracic and abdominal aortas, subendothelial macrophage-derived foam cells contained a high proportion of the silver grains (40-60% of the total) and accounted for between 30% and 40% of the lesion volume. In contrast, smooth muscle cells in the lesions contained only 7-10% of the total silver grains and accounted for approximately 20% of the lesion volume. Endothelial cells contained the most silver grains on a per-unit-volume basis by occupying only 1-2% of the lesion volume. However, the endothelium contained less than 5% of the total grains in lesions. The remaining silver grains (25-45%) were associated with the extracellular matrix, which constituted between 40% and 50% of the lesion volume. These data indicate that in the WHHL rabbit, subendothelial macrophage-derived foam cells avidly accumulate and metabolize LDL despite having few functional LDL receptors. PMID- 1637799 TI - Biological markers and the concept of psychiatric illness. PMID- 1637800 TI - The dimensional approach to clinical psychopharmacology: a polysemous concept. AB - The last decade has seen significant progress in the development and specific clinical application of selective psychotropes. The dimensional approach to clinical psychopharmacology views the behavioral targets of psychotropes as phenomena existing on a continuum and as components, in varying degrees, of most psychopathologies. The modern concept of dimension has been used in different contexts. In psychology it has a mathematical sense, whereas in biological psychiatry it is associated more with biological function. This paper reviews these two concepts and the recent models attempting to merge them into one. The heuristic value of the dimensional approach, as well as some of its pitfalls and new avenues of research, are discussed. PMID- 1637801 TI - [Use of low doses of bromocriptine in chronic schizophrenia resistant to neuroleptics. A preliminary study]. AB - In this work, we report the efficiency of bromocriptine (1.25 and 2.5 mg/day) in 9 neuroleptic resistant chronic schizophrenics. Following an initial four-week placebo period, the subjects successively received bromocriptine (1.25 mg/day), placebo and bromocriptine (2.5 mg/day). The 2 bromocriptine treatments significantly improved the global psychiatric symptomatology and different scores and factors related to the more specific schizophrenic symptomatology. An escape phenomenon seems to occur during the 4th week of the first bromocriptine treatment (1.25 mg/day) but is not observed with the second treatment (2.5 mg/day). All patients improved. PMID- 1637802 TI - Comparison of behavioral effects after single and repeated administrations of four benzodiazepines in three mice behavioral models. AB - The behavioral and clinical profiles of various benzodiazepines after acute and chronic treatment are not well defined and may differ. The aim of this study was to evaluate the behavioral profiles of alprazolam, bromazepam, diazepam and lorazepam in mice after single and repeated (every half-life for seven half lives) administrations using a stimulation-sedation test (actimeter), a myorelaxation test (rotarod), and an anxiolysis test ("four plates"). A dose range from 0.03 to 4 mg/kg was used. A single administration of alprazolam showed stimulating and anxiolytic effects which diminished after repeated administration. Lorezapam's sedative effect diminished but its anxiolytic effect increased upon repeated administration. Except for lorazepam, the myorelaxing effect of all four drugs increased after repeated treatment. These results suggest that the behavioral profile of benzodiazepines may not be identical during acute and chronic treatment. These differences may be present in clinical treatment and warrant investigation in humans. PMID- 1637803 TI - Sodium valproate and clonazepam for treatment-resistant panic disorder. AB - Sodium valproate (VA) and clonazepam (CLZ) were combined in the treatment of 4 patients with panic disorders (PD) who were resistant to several antipanic drug treatments. A significant improvement was found in the symptomatology of these patients, but relapses occurred when CLZ dosage was reduced. A potentiation of the GABAergic properties of VA and clonazepam is postulated. This combined treatment could be advantageous for some treatment-resistant PD patients but needs to be studied further. PMID- 1637804 TI - Phorbol ester-mediated downregulation of tropoelastin expression is controlled by a posttranscriptional mechanism. AB - Expression of tropoelastin, the principal precursor of elastic fibers, is tissue specific and is limited to a brief developmental period. Little is known, however, about the mechanisms that regulate the tissue- and temporal-specific expression of elastogenesis. The tropoelastin promoter contains putative phorbol ester responsive elements, or AP-1 binding sites, but the functional significance of these sequences is unknown. To test if tropoelastin expression is influenced by phorbol esters, we exposed elastogenic fetal bovine chondrocytes to 10(-7) M 12-O-tetradecanoylphorbol 13-acetate (TPA). Tropoelastin mRNA levels decreased greater than 10-fold in response to TPA, and this downregulation was paralleled by a decline in the secretion of tropoelastin protein into the culture medium. As determined by nuclear-runoff assay and transient transfection with a human gene promoter-CAT construct, tropoelastin transcription was unaffected after exposure to TPA. As indicated by actinomycin D experiments, the half-life of tropoelastin mRNA in control cells was about 20 h, but exposure to TPA resulted in an accelerated decay of the tropoelastin transcript (t1/2 = 2.2 h). These data indicate that downregulation of tropoelastin expression was controlled by a posttranscriptional mechanism and that the AP-1 elements in the bovine tropoelastin promoter may not be involved in regulation of production. PMID- 1637805 TI - Hydroxyethylene isostere inhibitors of human immunodeficiency virus-1 protease: structure-activity analysis using enzyme kinetics, X-ray crystallography, and infected T-cell assays. AB - Analogues of peptides ranging in size from three to six amino acids and containing the hydroxyethylene dipeptide isosteres Phe psi Gly, Phe psi Ala, Phe psi NorVal, Phe psi Leu, and Phe psi Phe, where psi denotes replacement of CONH by (S)-CH(OH)CH2, were synthesized and studied as HIV-1 protease inhibitors. Inhibition constants (Ki) with purified HIV-1 protease depend strongly on the isostere in the order Phe psi Gly greater than Phe psi Ala greater than Phe psi NorVal greater than Phe psi Leu greater than Phe psi Phe and decrease with increasing length of the peptide analogue, converging to a value of 0.4 nM. Ki values are progressively less dependent on inhibitor length as the size of the P1' side chain within the isostere increases. The structures of HIV-1 protease complexed with the inhibitors Ala-Ala-X-Val-Val-OMe, where X is Phe psi Gly, Phe psi Ala, Phe psi NorVal, and Phe psi Phe, have been determined by X-ray crystallography (resolution 2.3-3.2 A). The crystals exhibit symmetry consistent with space group P6(1) with strong noncrystallographic 2-fold symmetry, and the inhibitors all exhibit 2-fold disorder. The inhibitors bind in similar conformations, forming conserved hydrogen bonds with the enzyme. The Phe psi Gly inhibitor adopts an altered conformation that places its P3' valine side chain partially in the hydrophobic S1' pocket, thus suggesting an explanation for the greater dependence of the Ki value on inhibitor length in the Phe psi Gly series. From the kinetic and crystallographic data, a minimal inhibitor model for tight binding inhibition is derived in which the enzyme subsites S2-S2' are optimally occupied. The Ki values for several compounds are compared with their potencies as inhibitors of proteolytic processing in T-cell cultures chronically infected with HIV-1 (MIC values) and as inhibitors of acute infectivity (IC50 values). There is a rank-order correspondence, but a 20-1000-fold difference, between the values of Ki and those of MIC or IC50. IC50 values can approach those of Ki but are highly dependent on the conditions of the acute infectivity assay and are influenced by physiochemical properties of the inhibitors such as solubility. PMID- 1637806 TI - Conformations, interactions, and thermostabilities of RNA and proteins in bean pod mottle virus: investigation of solution and crystal structures by laser Raman spectroscopy. AB - We report and interpret laser Raman spectra of the three virion components of bean pod mottle virus (BPMV). The top component of BPMV is an empty capsid; middle and bottom components package the RNA2 and RNA1 genome segments, respectively. All components were investigated as both single crystals and aqueous solutions, the latter over wide ranges of temperature and ionic strength. The isolated RNA2 molecule of BPMV middle component was also investigated in both H2O and D2O solutions. The results permit assessment of RNA and protein structures, their mutual interactions in the virions, and their conformational thermostabilities and comparison of these structural characteristics for solution and crystal states of the particles. The principal findings of this study are (i) The extent of ordered A-form backbone (74%) and of base pairing (38% AU + 22% GC) in unpackaged (aqueous) RNA2 are significantly altered by packaging. The A-form secondary structure of RNA2 is increased by 12 +/- 4%, and guanine base interactions are also substantially increased with packaging. (ii) The thermostability of Raman-monitored secondary structure of unpackaged RNA2 (Tm approximately 43 degrees C) is greatly increased in the packaged state (Tm approximately 53 degrees C). This increase corresponds to a stabilization of the A-form backbone geometry in 15 +/- 5% of genome nucleotides. (iii) Packaging of RNA2 in the middle component stabilizes subunit-subunit interactions of the capsid, as evidenced by a thermal denaturation temperature Td approximately 65 degrees C for the virion, compared with Td approximately 55 degrees C for the empty capsid. (iv) Raman marker-band shifts implicate the purine 7N sites of RNA2 and aromatic side chains of subunits as the principal targets for RNA-subunit interaction. (v) At the conditions of the present experiments (8 degrees C, pH approximately 7, moderate ionic strength), the subunit secondary structures observed for solutions of the top, middle, and bottom components are indistinguishable by Raman spectroscopy from secondary structures observed for corresponding crystalline samples. (vi) On the other hand, side chains of subunits in the top component (empty capsid) yield significantly different Raman intensities in crystalline and solution states. These differences are interpreted as the result of changes in a small number of side-chain environments between crystal and solution. (vii) Similarly, small differences exist between RNA Raman markers of crystalline and aqueous virions, which are attributed to altered environments of nucleotide residues and to a small increase in the amount of A form backbone geometry upon going from the crystal to the solution.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1637807 TI - Unfolding of trp repressor studied using fluorescence spectroscopic techniques. AB - The unfolding properties of the trp repressor of Escherichia coli have been studied using a number of different time-resolved and steady-state fluorescence approaches. Denaturation by urea was monitored by the average fluorescence emission energy of the intrinsic tryptophan residues of the repressor. These data were consistent with a two-state transition from dimer to unfolded monomer with a free energy of unfolding of 19.2 kcal/mol. The frequency response profiles of the fluorescence emission brought to light subtle urea-induced modifications of the intrinsic tryptophan decay parameters both preceding and following the main unfolding transition. The increase of lifetime induced by urea required higher concentrations of urea than the increase in the total intensity described by Gittelman and Matthews [(1990) Biochemistry 29, 7011]. This indicates that the intensity increase has both dynamic and static origins. To assess the effect of tryptophan binding upon repressor stability, and to determine whether repressor oligomerization would be detectable in an unfolding experiment, we examined denaturation profiles of repressor labeled with the long-lived fluorescence probe 5-(dimethylamino)naphthalene-1-sulfonyl (DNS), by monitoring the average rotational correlation time of the probe. These experiments revealed a protein concentration dependent transition at low urea concentrations. This transition was promoted by tryptophan binding. We ascribe this transition to urea-induced dissociation of repressor tetramers. The main unfolding transition of the dimer to unfolded monomer was also observable using this technique, and the free energies associated with this transition were 18.3 kcal/mol in the absence of tryptophan and 24.1 kcal/mol in its presence, demonstrating that co-repressor binding stabilizes the repressor dimer against denaturation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637808 TI - Speed of intersubunit communication in proteins. AB - To determine the speed of communication between protein subunits, time-resolved absorption spectra were measured following partial photodissociation of the carbon monoxide complex of hemoglobin. The experiments were carried out using linearly polarized, 10-ns laser pulses, with the polarization of the excitation pulse both parallel and perpendicular to the polarization of the probe pulse. The substantial contribution to the observed spectra from photoselection effects was eliminated by isotropically averaging the polarized spectra, allowing a detailed comparison of the kinetics as a function of the degree of photolysis. These results show that prior to 1 microsecond both geminate ligand rebinding and conformational relaxation are independent of the number of ligands dissociated from the hemoglobin tetramer, as expected for a two-state allosteric model. After this time the kinetics depend on the ligation state of the tetramer. The conformational relaxation at 10 microseconds can be interpreted in terms of the two-state allosteric model as arising from the R to T quaternary conformational change of both unliganded and singly liganded molecules. These results suggest that communication between subunits requires about 1 microsecond and that the mechanism of the communication which occurs after this time is via the R to T conformational change. The optical anisotropy provides a novel means of accurately determining the extinction coefficients of the transient photoproduct. The decay in the optical anisotropy, moreover, provides an accurate determination of the rotational correlation time of 36 +/- 3 ns. PMID- 1637809 TI - Ligand binding to the membrane-bound acetylcholine receptor from Torpedo marmorata: a complete mathematical analysis. AB - We have studied by means of equilibrium binding and kinetic experiments the interaction of the membrane-bound nicotinic acetylcholine receptor (nACHR) from Torpedo marmorata with [3H]acetylcholine and the fluorescent agonist NBD-5 acylcholine. In agreement with previous studies by others, we observed the preexistence, in the absence of ligand, of an equilibrium between two states of the nAChR, one with high affinity and the other with low affinity for agonist. As additional requirements for a minimal reaction scheme, we recognized (i) the existence of two ligand-binding sites, each of which may exist in two conformational states when occupied, and (ii) ligand-induced transitions between these conformations. Employing a special form of the allosteric model which considers these requirements, we then developed a suitable algorithm in order to simultaneously fit the whole set of equilibrium binding and kinetic data obtained for the two ligands. In this way we determined for a minimal model of the mechanism of action of the nAChR the complete set of rate constants and KD values involved. With these values available, we were able to simulate the rise and fall in the concentrations of individual receptor-ligand complexes and conformations occurring in the course of excitatory events at the electrocyte synapse. The membrane environment of the nAChR plays a decisive role with respect to the rates of conformational change of the nAChR occurring in the course of ligand interaction. Thus, artificial changes in membrane structure and composition can speed up by several orders of magnitude the rate of conformational change ("desensitization"). A proper structure of the surrounding membrane hence is a prerequisite for the physiological function of the membrane-embedded nAChR. PMID- 1637810 TI - Lateral diffusion in the liquid phases of dimyristoylphosphatidylcholine/cholesterol lipid bilayers: a free volume analysis. AB - The technique of fluorescence recovery after photobleaching is used to perform an extensive study of the lateral diffusion of a phospholipid probe in the binary mixture dimyristoylphosphatidylcholine/cholesterol, above the melting temperature of the phospholipid. In the regions of the phase diagram where a single liquid phase exists, diffusion can be quantitatively described by free volume theory, using a modified Macedo-Litovitz hybrid equation. In the liquid-liquid immiscibility region, the temperature dependence of the diffusion coefficient is in excellent agreement with current theories of generalized diffusivities in composite two-phase media. A consistent interpretation of the diffusion data can be provided based essentially on the idea that the primary effect of cholesterol addition to the bilayer is to occupy free volume. On this basis, a general interpretation of the phase behavior of this mixture is also proposed. PMID- 1637811 TI - Calcium-43 NMR studies of calcium-binding lysozymes and alpha-lactalbumins. AB - The calcium-binding properties of equine and pigeon lysozyme as well as those of bovine and human alpha-lactalbumin were investigated by 43Ca NMR spectroscopy. All proteins were found to contain one high-affinity calcium-binding site. The chemical shifts, line widths, relaxation times (T1 and T2), and quadrupole coupling constants for the respective 43Ca NMR signals were quite similar; this is indicative of a high degree of homology between the strong calcium-binding sites of these four proteins. The measured chemical shifts (delta approximately 3 to -7 ppm) and quadrupole coupling constants (chi approximately 0.7-0.8 MHz) are quite distinct from those observed for typical EF-hand calcium-binding proteins, suggesting a different geometry for the calcium-binding loops. The correlation times for bound calcium ions in these proteins were on the order of 4 8 ns, indicating that the flexibilities of these binding sites are limited. The apparent pKa values for the high-affinity sites ranged from 3.4 to 4.7, confirming the participation of carboxylate-containing residues in the coordination of the calcium ion. Competition experiments with EDTA showed that the affinities of these proteins for calcium follow the series bovine alpha lactalbumin approximately human alpha-lactalbumin greater than pigeon lysozyme greater than equine lysozyme (KD approximately 5 x 10(-8) to 10(-6) M). Evidence for the existence of a second weak calcium-binding site (KD = 3 x 10(-3) M) was obtained for bovine alpha-lactalbumin, but not for the other proteins studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637812 TI - A single-stranded DNA exonuclease from Schizosaccharomyces pombe. AB - We have purified to near homogeneity a DNA exonuclease from meiotic cells of Schizosaccharomyces pombe. The enzyme, designated exonuclease II (ExoII), had an apparent molecular weight of 134,000 and was abundant in the cell. It specifically degraded single-stranded DNA in the 5'----3' direction with an apparent Km for 5' DNA ends of 3.6 x 10(-11) M and produced 5' deoxynucleoside monophosphates. Its mode of degradation is similar to that of the RecJ protein from Escherichia coli; ExoII may, therefore, be involved in genetic recombination and DNA damage repair. PMID- 1637813 TI - Structure of the DNA interstrand cross-link of 4,5',8-trimethylpsoralen. AB - 4,5',8-Trimethylpsoralen (TMP) cross-links a 5' TpA or a 5' ApT site by photoreacting with one thymine moiety in each DNA strand. We are interested in whether psoralen interstrand cross-links all share one structure or whether there are significant differences. In this paper, we employed a rapid method for probing the structure of the cross-link by making a series of TMP cross-linked duplexes containing specific base-pair mismatches. The relative stability provided by a base pair can be correlated with neighboring base pairs by comparing the extents of gel retardation when base-pair mismatches happen in each position. From our studies, we infer that with respect to the furan-side strand, the 5'T.A base pair of the two T.A base pairs in the TpA site is not hydrogen bonded. Immediately on each side of the cross-linked TpA site is a highly stabilized base pair. Next, a region of decreased stability occurs in each arm of a cross-linked duplex and these base pairs of least stability are located farther away from the cross-linked thymines as the lengths of the arms of the cross linked helix increase. Finally, even in 7 M urea at 49 degrees C the cross-linked helix is hydrogen bonded at both ends of a duplex of 22 base pairs. We propose that the structures of interstrand cross-links in DNA vary appreciably with the DNA sequence, the length of the DNA duplex, and the structures of the DNA cross linking agents. PMID- 1637814 TI - Recognition of a guanine-cytosine base pair by 8-oxoadenine. AB - Two oligodeoxyribonucleotides, d-CTTCTTTTTTATTTT, I(A), and d-ATTATTTTTTATTTT, II(A), where C is 5-methylcytosine and A is 8-oxoadenine, were prepared and their interactions with the duplex d-GAAGAAAAAAYAAAA/d-TTTTZTTTTTTCTTC, III.IV(Y.Z), were studied. Oligomers I(A) and II(A) each form triplexes with III.IV(G.C) at temperatures below 20 degrees C as shown by continuous variation experiments, melting experiments, and circular dichroism (CD) spectroscopy. The CD spectra of these triplexes are almost identical to those formed by I(C) and II(C), oligomers which contain cytosine in place of 8-oxoadenine. This suggests that the 8 oxoadenine-containing triplexes have conformations which are very similar to those of the cytosine-containing triplexes. The melting temperature (Tm) for dissociation of the third strand of triplex II.III.IV(A.G.C) is 22 degrees C at pH 7.0 and 8.0, whereas the Tm of the corresponding transition in triplex II.III.IV(C.G.C) decreases from 28 degrees C at pH 7.0 to 17 degrees C at pH 8.0. The pH dependence of the Tm in the latter triplex reflects the necessity of protonating the N-3 of cytosine in order for it to form two hydrogen bonds with G of the G.C base pair. It appears that the keto form of 8-oxoadenine can potentially form two hydrogen bonds with the N-7 and O-6 atoms of G of the G.C base pair, when the 8-oxoadenine is in the syn conformation and in contrast to cytosine does not require protonation of the base. Oligomer I(A) does not form triplexes with III.IV(Y.Z) when Y.Z is A.T or T.A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637815 TI - Translesion DNA synthesis in the dihydrofolate reductase domain of UV-irradiated CHO cells. AB - The studies that document the coupling of strand-specific DNA repair to transcription of active genes exclude replicated DNA from the analysis. Yet cyclobutane pyrimidine dimers (CPD) induced by ultraviolet light (UV) persist in most of the genome in surviving Chinese hamster ovary (CHO) cells. The mechanisms that allow DNA replication to occur in the presence of damaged templates are poorly understood. We have investigated the distribution of CPD in the dihydrofolate reductase gene (DHFR) domain in replicated DNA. CHO B11 cells were incubated in the presence of BrdUrd after UV irradiation; the replicated DNA was separated from the unreplicated DNA by isopycnic sedimentation in CsCl, and then the parental and daughter strands were resolved in alkaline CsCl. We determined the fraction of a 14-kb KpnI fragment of the DHFR gene that was resistant to digestion by T4 endonuclease V, a CPD-specific enzyme. In both parental and unreplicated DNA, approximately 80% of the CPD were removed from the transcribed strands while approximately 20% were removed from the nontranscribed strands of DHFR within 24 h. In a 15-kb KpnI fragment that contains an origin of replication and is located approximately 15 kb downstream of DHFR, we found very low repair levels, whether it had been replicated or not. We detected no CPD in the daughter strands of either fragment analyzed. These results suggest that the replication forks can move through the damaged DNA in the absence of significant levels of repair or strand exchange and that the repair of CPD is not affected by replication in these cells. PMID- 1637816 TI - Human dihydrofolate reductase: reduction of alternative substrates, pH effects, and inhibition by deazafolates. AB - The kinetics of the NADPH-dependent reduction of 7,8-dihydrofolate, folate, and 7,8-dihydrobiopterin by human dihydrofolate reductase have been examined over the pH range from 4.0 to 9.5. The V and V/K profiles obtained with the three substrates indicate that a single ionizing residue at the active site of the enzyme must be protonated for catalysis. Both the maximum velocity of the reactions and the rate of interaction of the substrates with the enzyme-NADPH complex decrease in the order dihydrofolate greater than dihydrobiopterin much greater than folate. From the pK values of the V/K profiles, it can be concluded that, while dihydrofolate behaves as a sticky substrate and dihydrobiopterin exhibits slight stickiness, folate is not a sticky substrate. Further support for this conclusion comes from the results of deuterium isotope effects. The pK values obtained from both the V and V/Kfolate profiles are similar to the intrinsic pK value of 5.6 for both the free enzyme and the enzyme-NADPH complex. The folate analogue, 5-deazafolate, is not a substrate, but it undergoes strong interaction with the enzyme. This interaction, which is enhanced by the presence of NADPH, is due to protonation of the bound ligand that does not involve the single ionizing group at the active center of the enzyme. Difference spectra yield evidence for the protonation of bound 5-deazafolate and show that, on binding to the enzyme-NADPH complex, the pK of the N-8 atom is raised to about 10 from a value of about 4 in solution. The results are in accord with those of a recent paper on the three-dimensional structure of the enzyme-5-deazafolate complex [Davies, J.F., Delcamp, T.J., Prendergast, N.J., Ashfors, V.A., Freisheim, J.H., & Kraut, J. (1990) Biochemistry 29, 9467-9479] which indicate that there is hydrogen bond formation between N-8 of the ligand and the carbonyl group of Ile-7. However, the present findings do not support the idea that bound 5-deazafolate resembles the transition-state complex for folate reduction. Quinazolines also interact strongly with the enzyme but in a pH-independent manner. The dissociation constants for the binary complexes are an order of magnitude lower than that for the binding to the enzyme of unprotonated 5 deazafolate. This difference reflects the hydrophobic nature of the amino acid residues at the active site that are near the N-5 and N-8 nitrogens of bound pterins. PMID- 1637817 TI - Interaction of rabbit muscle aldolase at high ionic strengths with vanadate and other oxoanions. AB - Reductive, nonreductive, and photolytic interactions of vanadate with fructose 1,6-bisphosphate aldolase were examined and used to explore the interactions of oxoanions with aldolase. Aldolase is known to interact strongly with oxoanions at low ionic strength and weakly at higher ionic strength. Oxoanions inhibit aldolase competitively with respect to fructose 1,6-bisphosphate although the location of the oxoanion binding site on aldolase remains elusive. In this work, the interaction of aldolase with a series of oxoanions was compared at ionic strength approaching physiologic levels. The size and shape of the anion were important for the effective binding to aldolase, and no significant increase in affinity for aldolase was observed by the addition of alkyl groups to the oxoanions. Vanadate competitively inhibits aldolase in a manner analogous to the other oxoanions. Since vanadate solutions contain a mixture of vanadate oxoanions, the nature of the inhibition was determined using a combination of enzyme kinetics and 51V NMR spectroscopy. Aldolase contains a significant number of thiol functionalities, and as expected, vanadate undergoes redox chemistry with them, generating an irreversibly inhibited aldolase. This oxidative chemistry was attributed to the vanadate tetramer, whereas vanadate dimer was a reversible inhibitor. Vanadate monomer does not significantly interact with aldolase reversibly or irreversibly. Vanadyl cation has the lowest inhibition constant under these high ionic strength conditions. Using Yonetani-Theorell analysis, it appears that phosphate, pyrophosphate, and sulfate bind to the same site on aldolase, whereas vanadate, arsenate, and molybdate bind to another site. UV light-induced photocleavage of aldolase by vanadate was examined, and the loss of aldolase activity was correlated with cleavage of the aldolase subunit. Further studies using vanadium as a probe should reveal details on the location of the vanadate and vanadyl cation binding sites. This study suggests several sites on aldolase will accommodate oxoanions, and one of these sites also accommodates vanadyl cation. PMID- 1637818 TI - Stereochemical course of tyramine oxidation by semicarbazide-sensitive amine oxidase. AB - Two semicarbazide-sensitive amine oxidases (SSAO's) from bovine and porcine aortic tissue were partially purified and characterized, and the stereochemical course of amine oxidation was evaluated. The porcine and bovine SSAO's were membrane bound glycoproteins, with Km values for benzylamine of 8 and 16 microM, respectively. The reactivity of SSAO with semicarbazide and phenylhydrazine suggests that the cofactor is a carbonyl type molecule. The stereochemical course of the bovine and porcine aortic semicarbazide-sensitive amine oxidase reaction was investigated using chiral tyramines, deuterated at C-1 and C-2, and 1H-NMR spectroscopy to establish the loss or retention of deuterium in product p hydroxyphenethyl alcohols. The preferred mode of tyramine oxidation was found to occur with the loss of pro-S proton at C-1, coupled with solvent exchange into C 2, a pattern which has not been observed for any copper amine oxidase examined to date. The solvent exchange reaction also occurred stereospecifically, with loss from and reprotonation to the pro-R position, suggesting that these two processes occur from the same face of the enamine double bond. PMID- 1637819 TI - 3-Hydroxy-3-methylglutaryl coenzyme A lyase: affinity labeling of the Pseudomonas mevalonii enzyme and assignment of cysteine-237 to the active site. AB - Pseudomonas mevalonii 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lyase is irreversibly inactivated by the reactive substrate analog 2-butynoyl-CoA. Enzyme inactivation, which follows pseudo-first-order kinetics, is saturable with a KI = 65 microM and a limiting k(inact) of 0.073 min-1 at 23 degrees C, pH 7.2. Protection against inactivation is afforded by the competitive inhibitor 3 hydroxyglutaryl-CoA. Labeling of the bacterial enzyme with [1-14C]-2-butynoyl-CoA demonstrates that inactivation coincides with covalent incorporation of inhibitor, with an observed stoichiometry of modification of 0.65 per site. Avian HMG-CoA lyase is also irreversibly inactivated by 2-butynoyl-CoA with a stoichiometry of modification of 0.9 per site. Incubation of 2-butynoyl-CoA with mercaptans such as dithiothreitol results in the formation of a UV absorbance peak at 310 nm. Enzyme inactivation is also accompanied by the development of a UV absorbance peak at 310 nm indicating that 2-butynoyl-CoA modifies a cysteine residue in HMG-CoA lyase. Tryptic digestion and reverse-phase HPLC of the affinity-labeled protein reveal a single radiolabeled peptide. Isolation and sequence analysis of this peptide and a smaller chymotryptic peptide indicate that the radiolabeled residue is contained within the sequence GGXPY. Mapping of this peptide within the cDNA-deduced sequence of P. mevalonii HMG-CoA lyase [Anderson, D. H., & Rodwell, V. W. (1989) J. Bacteriol. 171, 6468-6472] confirms that a cysteine at position 237 is the site of modification. These data represent the first identification of an active-site residue in HMG-CoA lyase. PMID- 1637820 TI - Purification of human S-adenosylmethionine decarboxylase expressed in Escherichia coli and use of this protein to investigate the mechanism of inhibition by the irreversible inhibitors, 5'-deoxy-5'-[(3-hydrazinopropyl)methylamino]adenosine and 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine. AB - Human S-adenosylmethionine decarboxylase (AdoMetDC) was expressed in high yield in Escherichia coli using the pIN-III(lppP-5) expression vector and purified to apparent homogeneity using affinity chromatography on methylglyoxal bis(guanylhydrazone)-Sepharose. The inactivation of the purified enzyme by 5' deoxy-5'-[(3-hydrazinopropyl)methylamino]adenosine (MHZPA) was accompanied by an increase in absorbance at 260 nm of the large subunit. This increase was equivalent to the addition of 1 molecule of MHZPA. After digestion with the protease Lys-C, a peptide that contained the bound MHZPA was isolated and found to have the amino acid composition consistent with that expected from the amino terminus of the large subunit. These results indicate that MHZPA inactivates AdoMetDC by forming a hydrazone derivative at the pyruvate prosthetic group. Inactivation of AdoMetDC by 5'-([(Z)-4-amino-2-butenyl]methylamino]-5' deoxyadenosine (AbeAdo) led to the appearance of a new peptide peak in the Lys-C protease digest. This peptide had the sequence ASMFVSK. This agrees with the expected sequence from the amino terminus, which is pyruvoyl-SMFVSK, with the exception that the pyruvate has been converted to alanine. Direct gas-phase sequencing of the large subunit of the enzyme also indicated the presence of alanine at the amino terminus after inactivation with AbeAdo. These results indicate that this inhibitor leads to transamination of the pyruvate prosthetic group. Since the pyruvate is covalently linked to the protein, its replacement by alanine leads to an irreversible inactivation of AdoMetDC. PMID- 1637821 TI - In pursuit of the molecular structure of amyloid plaque: new technology provides unexpected and critical information. PMID- 1637822 TI - Progress in establishing the rate-limiting features and kinetic mechanism of the glyceraldehyde-3-phosphate dehydrogenase reaction. AB - Primary hydrogen isotope effects and steady-state kinetics have been used to study the mechanism of glyceraldehyde-3-phosphate (GAP) dehydrogenase at pH 8.6. The isotope effect determined by using GAP-1d was unity and independent of arsenate (used as the acyl acceptor) and NAD+ concentrations when the aldehyde substrate was at saturating concentrations. At low GAP concentrations (apparent V/K conditions), the primary hydrogen isotope effect (H/D) was in the range of 1.40-1.52 and independent of arsenate and NAD+ concentrations. Apparent V/K for NAD+ was independent of GAP concentration, and apparent V/K for GAP was independent of NAD+ concentration. The dependence of apparent V/K for GAP on arsenate concentration was more complex but extrapolated to nonzero V/K at the zero-arsenate intercept. These observations are consistent with the general features of the Segal and Boyer (1953) mechanism for the reaction. PMID- 1637823 TI - p-aminobenzoate synthesis in Escherichia coli: kinetic and mechanistic characterization of the amidotransferase PabA. AB - p-Aminobenzoic acid (PABA) is an important precursor in the bacterial biosynthetic pathway for folate enzymes. This biosynthesis requires three separate proteins: PabA, PabB, and PabC. Together PabA and PabB convert glutamine and chorismate to glutamate and 4-amino-4-deoxychorismate. This aminochorismate is subsequently transformed to PABA by PabC. In this study, PabA from Escherichia coli has been purified to homogeneity from an overproducing construct and found to have no detectable glutaminase activity until addition of the E. coli PabB subunit. PabB forms a 1:1 complex with PabA to yield a glutaminase k(cat) of 17 min-1. The addition of chorismate, the substrate of PabB, induces a 2-fold increase of k(cat) as well as a 3-fold increase of Km for glutamine. The PabA/PabB complex has Kd less than 10(-8) M but does not form a stable complex isolable by gel filtration. Studies with the glutamine affinity label diazooxonorleucine (DON) reveal it is an inactivator of the glutaminase activity of the PabA/PabB complex, but DON does not alkylate and inactivate PabA alone. Similarly, while isolated PabA shows no tendency to form a glutamyl-enzyme intermediate, the PabA/PabB complex forms a covalent intermediate with [14C]glutamine on PabA that accumulates to 0.56 mol/mol in hydrolytic turnover. PabA is thus a conditional glutaminase, activated by 1:1 complexation with PabB. PMID- 1637824 TI - Topological mapping of the active sites of cytochromes P4502B1 and P4502B2 by in situ rearrangement of aryl-iron complexes. AB - Cytochrome P4502B1 reacts with phenylhydrazine or phenyldiazene to give an iron phenyl complex that oxidatively rearranges in situ to the two N phenylprotoporphyrin IX regioisomers with the phenyl group on pyrrole rings A (NA) and D (ND) [Swanson, B. A., Dutton, D. R., Lunetta, J. M., Yang, C. S., & Ortiz de Montellano, P. R. (1991) J. Biol. Chem. 266, 19258-19264]. The conclusion that the active site of cytochrome P4502B1 is open above pyrrole rings A and D but not B and C is extended here by studies with larger arylhydrazines. The N-arylprotoporphyrin IX standards required for product identification were obtained by reaction of the arylhydrazines with equine myoglobin. Cytochrome P4502B1 aryl-iron complex formation followed by oxidative shift of the aryl group produces the following N-aryl-protoporphyrin IX NA:ND regioisomer ratios: phenylhydrazine (39:61), 3,5-dimethylphenylhydrazine (29:71), 4-tert butylhydrazine (25:75), 2-naphthylhydrazine (less than 2:greater than 98), and 4 (phenyl)phenylhydrazine (87:13). Electron-withdrawing substituents (as in 3,5 dichlorophenyl) prevent the aryl group shift. The increase in the proportion of the ND regioisomer with increasing bulk of the aryl group suggests that the region over pyrrole ring A is more sterically encumbered than that over pyrrole ring D. The regiospecificity is reversed, however, with 4 (phenyl)phenylhydrazine, which primarily gives the NA regioisomer. This reversal suggests that the active site has a sloping roof that is higher over pyrrole ring A than pyrrole ring D and that provides a larger steric barrier to the shift of tall aryl moieties than the barrier over pyrrole ring A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637825 TI - Gene cluster of the energy-transducing NADH-quinone oxidoreductase of Paracoccus denitrificans: characterization of four structural gene products. AB - In previous reports from our laboratory, the three structural genes (NQO1, NQO2, and NQO3) of the energy-transducing NADH-quinone oxidoreductase of Paracoccus denitrificans were characterized [Xu, X., Matsuno-Yagi, A., & Yagi, T. (1991) Biochemistry 30, 6422-6428; (1991) Biochemistry 30, 8678-8684; (1992) Arch. Biochem. Biophys. 296, 40-48]. In this report, the four structural genes NQO4, NQO5, NQO6, and NQO7 of the same Paracoccus denitrificans oxidoreductase were cloned and sequenced. On the basis of sequence homology and immunological cross reactivity, these genes encode counterparts of the 49-, 30-, and 20-kDa polypeptides and the mitochondrial DNA ND3 polypeptides of bovine mitochondrial complex I. These seven structural genes were found to be located in the same gene cluster. The order of the seven structural genes of the Paracoccus NADH-quinone oxidoreductase in the gene cluster is NQO7, NQO6, NQO5, NQO4, NQO2, NQO1, and NQO3. Upstream of the NQO7 gene, an open reading frame encoding a predicted polypeptide homologous to the UV repair enzyme A of Escherichia coli and Micrococcus lysodeikticus was detected. The 5'-terminus of the gene cluster carrying the Paracoccus NADH-quinone oxidoreductase was studied, and the possible promoter region is discussed. The NQO4 and NQO5 genes appear to code for the M(r) 48,000 and 21,000 polypeptides of the isolated Paracoccus NADH dehydrogenase complex [Yagi, T. (1986) Arch. Biochem. Biophys. 250, 302-311] on the basis of amino acid analyses and N-terminal protein sequence analyses. The antisera to the bovine complex I 49- and 30-kDa polypeptides cross-reacted with the Paracoccus 48 and 21-kDa subunits, respectively. PMID- 1637826 TI - Infrared study of the L, M, and N intermediates of bacteriorhodopsin using the photoreaction of M. AB - Infrared spectroscopy is used to characterize the transitions in the photocycle of bR involving the M intermediate. It has been shown previously that in this part of the photocycle a large protein conformational change takes place that is important for proton pumping. In this work we separate the spectra of the L, M, and N intermediates in order to better describe the timing of the molecular changes. We use the photoreaction of the M intermediate to separate its spectrum from those of L and N. At temperatures between 220 and 270 K a mixture of M and L or N is produced by illumination with green light. Subsequent blue illumination selectively drives M back into the ground state and the difference between the spectra before and after blue excitation yields the spectrum of M. Below about 250 K and L/M mixture is separated; at higher temperatures an M/N mixture is seen. We find that the spectrum of M is identical in the two temperature regions. The large protein conformational change is seen to occur during the M to N transition. Our results confirm that Asp-96 is transiently deprotonated in the L state. The only aspartic protonation changes between M and bR are the protonation of Asp-85 and Asp-212 that occur simultaneously during the L to M transition. Blue-light excitation of M results in deprotonation of both. The results suggest a quadrupolelike interaction of the Schiff base, Asp-85, Asp-212, and an additional positive charge in bR. PMID- 1637827 TI - Characterization of the adenine binding sites of two Dolichos biflorus lectins. AB - The seed lectin and a stem and leaf lectin (DB58) from Dolichos biflorus have high-affinity hydrophobic sites that bind to adenine. The present study employs a centrifugal filtration assay to characterize these sites. The seed lectin contains two identical sites with Ka's of 7.31 x 10(5) L/mol whereas DB58 has a single site with a Ka of 1.07 x 10(6) L/mol. The relative affinities of these sites for a host of adenine analogs and derivatives were determined by competitive displacement assays. The most effective competitors for adenine were the cytokinins, a class of plant hormone, for which the lectins had apparent Ka's of 1.96 x 10(5)-4.90 x 10(4) L/mol. Direct binding of the cytokinin 6 (benzylamino)purine (BAP) to both lectins showed positive cooperativity for only the seed lectin, indicating the interaction of this ligand with more than one class of hydrophobic binding site. Fluorescence enhancement assays demonstrate cooperativity between hydrophobic sites of the seed lectin and also suggest that BAP binds to more than one class of site. PMID- 1637828 TI - cDNAs and deduced amino acid sequences of subunits in the binding component of mouse bactericidal factor, Ra-reactive factor: similarity to mannose-binding proteins. AB - The complement-dependent bactericidal factor, Ra-reactive factor, binds specifically to Ra polysaccharide, which is common to some strains of Gram negative enterobacteria, and its is a complex of proteins composed of a polysaccharide-binding component and a component that is presumably responsible for the complement activation. The former component consists of two different 28 kDa polypeptides, P28a and P28b. We determined the partial amino acid sequences of P28a and P28b, and the results indicated that these polypeptides were similar to two species of mannose-binding protein, MBP-C and MBP-A (alternative names, liver and serum mannan-binding proteins, respectively), which have been isolated from rat liver and/or serum [Drickamer, K., Dordal, M. S., & Reynolds, L. (1986) J. Biol. Chem. 261, 6878-6887; Oka, S., Itoh, N., Kawasaki, T., & Yamashina, I. (1987) J. Biochem. 101, 135-144]. Thus, we cloned the respective cDNAs, using as probes synthetic oligonucleotides for which the sequences had been deduced from the amino acid sequences of P28a and P28b and of rat MBP cDNAs. The primary structures of P28a and P28b deduced from the cloned cDNAs are homologous to one another. They have three domains, a short NH2-terminal domain, a collagen-like domain, and a domain homologous to regions of some carbohydrate-binding proteins, as has been reported for rat MBPs. Southern and Northern blotting analyses using these cDNAs indicated that the P28a and P28b polypeptides are the products of two unique mouse genes which are expressed in hepatic cells. PMID- 1637829 TI - Characterization of the oligosaccharide structures on recombinant human prorenin expressed in Chinese hamster ovary cells. AB - Prorenin was isolated by immunoprecipitation from the culture medium of Chinese hamster ovary cells transfected with a human prorenin cDNA. The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size exclusion chromatography and treatment with specific glycosidases and methylation analysis. Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4 branched triantennary (3%), and biantennary (43%) structures. The majority of all complex type structures are core-fucosylated. Sialic acids are linked at the C-3 position of terminal galactose, and the degree of sialylation of the bi- and triantennary structures varies between nonsialylated and fully sialylated; no tetraatennary structure contains more than three sialic acid residues. Recombinant prorenin contains 4% hybrid-type structures, all of which carry a terminal sialic acid residue. The remaining 35% of the structures on the molecule are high mannose type, composed of 5, 6, or 7 mannose residues. Approximately 6% of the high mannose type structures and 10% of the hybrid structures are phosphorylated, as judged by their susceptibility to treatment with alkaline phosphatase. Compositional analysis of an unlabeled preparation of the protein suggested the presence of approximately 1.4 oligosaccharide units per molecule. PMID- 1637830 TI - Solution conformations of GM3 gangliosides containing different sialic acid residues as revealed by NOE-based distance mapping, molecular mechanics, and molecular dynamics calculations. AB - The conformation of the GM3 ganglioside, Neu5Ac alpha 2-3Gal beta 1-4Glc beta 1-1 Cer, and its analogs containing the Neu5Gc or Neu4Ac5Gc residues (Gc = glycolyl, CH2OHCO) was investigated in Me2SO-d6 solution with the aid of a distance-mapping procedure based on rotating-frame NOE contacts, with hydroxyl protons being used as long-range sensors defining the distance constraints. A pronounced flexibility found for both the Neu-Gal and Gal-Glc linkages was confirmed by 1000-ps molecular dynamics simulations. Similar results, although based on a smaller number of NOE constraints, were obtained for GM3 gangliosides anchored in mixed D2O/dodecylphosphocholine-d38 micelles and for the Neu5Ac-, Neu5Gc-, and Neu5,9Ac2-sialyllactoses dissolved in D2O. No noteworthy differences in conformational behavior of the glycan chains of the three gangliosides or sialyllactoses were observed in either of the media. PMID- 1637831 TI - Solution conformation of a peptide corresponding to the principal neutralizing determinant of HIV-1IIIB: a two-dimensional NMR study. AB - The 24 amino acid peptide RP135 corresponds in its amino acid sequence to the principal neutralizing determinant (PND) of the IIIB isolate of HIV-1. Although the sequence of the PND is highly variable, its central part, containing the sequence GPGR, is conserved in most HIV isolates. Using 2D NMR and CD spectroscopy, we have studied the conformation of RP135 and of two shorter versions: one (P547) that includes the GPGR sequence with the N-terminal part of the peptide and the other (P344) that includes GPGR and the C-terminal segment of RP135. In water, the C-terminal part of RP135 was found to exist in several transient turnlike conformations ("nascent helix"). A helical conformation was found to be stabilized by the addition of TFE. A transient turn was observed also in the GPGR sequence, both in water and in aqueous TFE solutions. While no nascent helix conformations could be observed in the N-terminal part of RP135 in water, a helical conformation was partially stabilized by the addition of TFE. The conformations of the two shorter versions of the peptide were similar to those of the corresponding parts of RP135, except that the transient turn in GPGR could not be detected in P547 dissolved in water. The turn in GPGR was previously predicted by Larosa et al. (1990) and was observed by Chandrasekhar et al. (1991) in the PND peptide of HIV-1MN (RP142), which shares only 56% identity with RP135. However, nascent helix conformations were not observed in aqueous solutions of RP142.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637832 TI - Interactions between DNA-bound transcriptional regulators of the Escherichia coli gal operon. AB - Regulation of the initiation of gene transcription from the gal operon of Escherichia coli is activated by the binding of CAP (catabolite activator protein) to a site centered at base pair -41.5 relative to the S1 start site of transcription. This operon is repressed by the specific binding of Gal repressor (GalR) to two operators, OE and OI, centered at -60.5 and +53.5, respectively. It has been proposed that this negative regulation results from the interaction of GalR dimers bound to OE and OI to form a protein-mediated "looped complex" [cf. Adhya, S. (1989) Annu. Rev. Genet. 23, 207-230]. In order to test whether DNA bound CAP would facilitate or inhibit the binding of GalR, the simultaneous binding of these proteins was studied by quantitative DNase I footprint titration analysis. These studies demonstrate that GalR binding is noncooperative in the presence and in the absence of CAP and that GalR and CAP bind to the gal operon independently. No evidence was found that CAP stabilizes a putative Gal repressor mediated protein-DNA looped complex. It has been shown that the gal operon can be negatively regulated by the binding of Lac repressor (LacI) to a gal operon in which OE and OI were both modified to be recognized by LacI [Haber, R., & Adhya, S. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 9683-9687]. In contrast to GalR, LacI binds to the chimeric gal operon with moderate cooperativity via the formation of a stable protein-DNA looped complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637833 TI - Structural comparisons of meizothrombin and its precursor prothrombin in the presence or absence of procoagulant membranes. AB - A stable form of meizothrombin derived from an active-site (Ser528----Ala) mutant of recombinant bovine prothrombin [Pei et al. (1991) J. Biol. Chem. 266, 9598 9604] has been used to determine the physical properties and conformation of meizothrombin both in solution and when bound to a procoagulant membrane. As determined with quasi-elastic light scattering, meizothrombin and prothrombin had similar molecular dimensions normal to a membrane (9.4 +/- 1.0 nm) and similar binding affinities to procoagulant membranes (1.8 +/- 0.2 microM at 0.4 M NaCl). However, meizothrombin had a greater tendency to form oligomers or aggregates in solution. The enhanced oligomerization of meizothrombin was also evidenced by a high apparent z-weighted molecular weight in equilibrium sedimentation experiments at low spin speeds. However, velocity sedimentation experiments performed at high spin speeds demonstrated the same sedimentation coefficient for meizothrombin (s20,w(0) = 4.7 +/- 0.2 S) as for prothrombin (s20,w(0) = 4.7 +/- 0.15 S). Circular dichroism measurements revealed minor differences in protein secondary structure between meizothrombin and prothrombin either in the presence or in the absence of phospholipid membranes, as reflected in an increased theta 222/theta 208 ratio in meizothrombin relative to prothrombin. The main endotherm of the meizothrombin thermal denaturation profile in a Ca(2+)-containing buffer, as determined by differential scanning calorimetry, was indistinguishable from that of prothrombin. However, in the presence of phosphatidylserine-containing membranes, the peak temperatures of denaturation profiles of meizothrombin were distinct from those of prothrombin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637834 TI - Resonance Raman study on the active-site structure of a cooperative hemerythrin. AB - Resonance Raman spectra were observed for the oxy and azidomet forms of a cooperative hemerythrin (Hr) isolated from Lingula unguis and a noncooperative Hr from Siphonosoma cumanense. The O-O stretching frequency of the oxy derivative of the L. unguis Hr was lower in the high-affinity form generated at pH 7.6 than in the low-affinity form generated at pH 6.2, while that of the S. cumanense Hr did not change at those two pH values. The Fe-O-Fe symmetric stretching mode of L. unguis azidomet-Hr exhibited a frequency shift between pH 7.6 and 6.2, while that of S. cumanense was not shifted. However, the corresponding band of the oxy form did not show a pH-dependent frequency change. Therefore, it is noted that the azidomet form is not a suitable model for studying a mechanism of cooperativity, contrary to the structural similarity between the oxy and azidomet forms. The Fe O2 as well as Fe-N3 stretching frequencies were found to have no relation with the oxygen affinity. Upon exchange of solvent from H2O to D2O, the O-O and Fe-O2 stretching modes of L. unguis Hr were shifted to higher and lower frequencies, respectively, and their magnitudes were the same for the high- and low-affinity forms. The same frequency shifts were observed for S. cumanense Hr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637835 TI - Isolation and characterization of a polyol-responsive monoclonal antibody useful for gentle purification of Escherichia coli RNA polymerase. AB - A modified enzyme-linked immunosorbent assay (ELISA) was used to screen monoclonal antibodies (MAbs) that react with Escherichia coli RNA polymerase for the ability to release the RNA polymerase in the presence of a low molecular weight polyhydroxylated compound (polyol) and a non-chaotropic salt. This assay, termed the ELISA-elution assay, identified 19 presumptive "polyol-responsive" MAbs out of a total of 218 antigen-specific MAbs screened. One of these MAbs, designated NT73, was examined in detail for the ability to release the antigen in response to various combinations of polyol and salt. Using NT73 conjugated to Sepharose, highly active RNA polymerase could be prepared rapidly by a single immunoaffinity chromatography step, replacing two lengthy chromatographic steps in our conventional purification procedure. Because NT73 reacts with the beta' subunit of RNA polymerase, a mixture of the core polymerase and holoenzyme was recovered from the immunoaffinity column. The holoenzyme (E sigma 70) could be separated from the core polymerase by subsequent chromatography on a Mono Q column. This demonstrates that polyol-responsive MAbs can be easily identified and characterized by the ELISA-elution assay. The use of polyol-responsive MAbs provides a means of adapting immunoaffinity chromatography to the purification of labile proteins. PMID- 1637836 TI - Structures of amphotericin B-cholesterol complex. AB - The structures of amphotericin B-cholesterol complex that forms a channel in a lipid membrane were analysed by molecular mechanics calculations. The symmetric complex consisting of eight rigid antibiotic and cholesterol molecules was considered. The presence of a continuous set of low-energy states of the complex with different values of the channel diameter was shown. These states are characterized by significant tilt of the amphotericin planes to the radial axis of the channel and by strong interaction between the charged ammonium and carboxyl groups of the antibiotic. Changes of the channel diameter may result in changes in pore permeability. PMID- 1637837 TI - Fatty acylation of a 55 kDa membrane protein of human erythrocytes. AB - The major palmitoylated human erythrocyte membrane protein has an M(r) of 55,000. It is distinct from the glucose transporter and is not derived from band 3 or ankyrin. It resists salt extraction suggesting a high affinity for the membrane. Pulse chase experiments demonstrate that palmitoylation is a dynamic process, and it may therefore have regulatory significance in membrane protein-protein or protein-lipid interaction. Slower dynamics of palmitoylation in erythrocytes from patients suffering from chronic myelogenous leukemia, which are less stable than normal erythrocytes, strengthen this view. PMID- 1637838 TI - Transport of procainamide in a kidney epithelial cell line LLC-PK1. AB - Transport of procainamide, an anti-arrhythmic drug, was investigated in LLC-PK1 kidney epithelial cell line. The uptake of procainamide by LLC-PK1 monolayers cultured in plastic dishes was temperature-dependent, saturable and inhibited by organic cations such as cimetidine and N-acetylprocainamide. An aminocephalosporin antibiotic, cephalexin, also inhibited procainamide uptake, but an organic anion, p-aminohippurate, did not. The uptake of procainamide was greater at an alkaline external pH than at an acidic pH. In addition, procainamide uptake increased when intracellular pH was decreased and the uptake decreased when the intracellular pH was increased by ammonium chloride treatment, indicating the involvement of an H+/procainamide antiport system in apical membrane. The basolateral to apical flux of procainamide across LLC-PK1 monolayers cultured on permeable supports was 2.5-times larger than the apical to basolateral flux, and only the former process was inhibited by other organic cations. These findings suggest that LLC-PK1 cells can transport procainamide by the organic cation transport system and that procainamide is transported unidirectionally from basolateral to apical side across the cell monolayers. PMID- 1637839 TI - Basolateral Cl-/HCO3- exchange in rat jejunum: evidence from H14CO3- uptake in membrane vesicles. AB - Bicarbonate transport across basolateral membrane vesicles from rat jejunal enterocyte was studied at 28 degrees C and pH 8.2. These experimental conditions make possible the determination of [14C]bicarbonate uptake. Inward gradients of Na+, K+, and Li+ did not stimulate HCO3- uptake, suggesting that a cotransport mechanism with these cations does not occur. On the contrary a countertransport of bicarbonate driven by a Cl- gradient was evidenced. The ability of other inorganic anions to exchange with HCO3- was examined and results indicate that Cl can be substituted by NO3-, Br- and SCN-. The Cl(-)-dependent HCO3- uptake was strongly inhibited by SITS and DIDS, whereas acetazolamide was ineffective: thus transfer of labelled CO2 is eliminated as a possible mode of HCO3- permeation. HCO3- uptake was also affected by the presence of superimposed membrane potentials, suggesting that a HCO3- conductive pathway is present in the jejunal basolateral membrane. These results show that there are no fundamental differences between data obtained performing H14CO3- and 36Cl- (previously reported) uptake experiments. PMID- 1637841 TI - K+/H+ exchange in yeast mitochondria: sensitivity to inhibitors, solubilization and reconstitution of the activity in proteoliposomes. AB - The K+/H+ exchange activity of the inner mitochondrial membrane was investigated in the yeast Saccharomyces cerevisiae. Swelling experiments in potassium acetate indicated that the K+/H+ exchange was active without any additional treatment after the mitochondria isolation, such as a Mg2+ depletion. As in mammalian mitochondria, the activity of yeast mitochondria was stimulated by increasing pH and was inhibited by the amphiphilic amines quinine and propranolol and by the carboxyl reagent dicyclohexylcarbodiimide. However, the activity was poorly inhibited by Mg2+ and consequently was only slightly stimulated by the Mg2+/H+ exchanger A23187. On the other hand, Zn2+ was very efficient for inhibiting the exchange and consequently the activity was strongly stimulated by the permeant metal-chelator o-phenanthroline. The [86Rb]Rb+ accumulation in mitochondria and mitoplasts was only partially inhibited by quinine and propranolol suggesting that part of the accumulation monitored under these conditions was due to cation leak through the inner membrane together with adsorption on the membrane. The DCCD-sensitive activity could be reconstituted from mitochondria and from mitoplasts solubilized with Triton X-100; this activity, measured by [86Rb]Rb+ accumulation, was quinine- and propranolol-sensitive. A spectrophotometric method, based on the capacity of negatively charged proteoliposomes to swell, was then developed in order to continuously follow the reconstituted activity. PMID- 1637840 TI - pHi controls cytoplasmic calcium in rat parotid cells. AB - The goal of this investigation was to determine if cytoplasmic pH (pHi) modulated the basal level of the concentration of calcium ions in the cytoplasm (Cai) in rat parotid cells. We investigated the effects of various experimental manipulations on both pHi and Cai as measured with BCECF and the calcium photoprotein aequorin, respectively. We found that various experimental manipulations that increased pHi, such as exposure of the cells to NH4Cl, a decrease of the partial pressure of CO2 or an increase in extracellular pH in the presence of nigericin invariably increased Cai. Moreover, experimental manipulations which lowered Cai, such as a reduction of extracellular [NaHCO3] or the removal of loaded NH4 invariably decreased Cai. Thus pHi and Cai are directly related in parotid cells. Since recent studies have shown that Cai directly influences pHi, we suggest that Cai-handling and pHi-handling are tightly linked in parotid cells. PMID- 1637842 TI - Conditions modulating the ionic selectivity of transport by monensin examined on Enterococcus hirae (Streptococcus faecalis) by 23Na-NMR and K+ atomic absorption. AB - Factors likely to modulate the ionic selectivity of monensin were examined on Enterococcus hirae (Streptococcus faecalis) in two states previously characterized: the resting (de-energized) cell and the active (energized) cell. Internal and external Na+ were followed by corresponding 23Na-NMR resonances K+ concentrations were measured by atomic absorption. For a given cellular population of de-energized cells, the apparent transport rates and the final cationic concentrations reached at the steady state were decreasing with the ionophore dose. Monensin was selective for sodium only at low concentrations, in the range 1 mM-10(-4) mM the transport was depending on the effective cationic gradients. Comparison of the activity curves for two cell populations (7.10(9) and 7.10(10) cells/ml) showed the importance of the ratios of monensin/mg phospholipid and also of the ratios of external/internal volumes. On energized cells, except for low monensin concentrations, the main effect was a K(+)-induced efflux and not a Na+ influx. Two factors were modulating the resulting selectivity of this ionophore: the response of the intrinsic bacterial carriers and the generation of the gradients (mainly the external pH) which were favourable to a K+/Na+ transport. Once again the results obtained for two cell populations could be compared, the determining factors were the ratio external/internal volume and the generation of the pH gradient. PMID- 1637843 TI - Tyrosine protein kinase activity in renal brush-border membranes. AB - Tyrosine protein kinase (TPK) activity was detected in rat renal brush-border membranes (BBM) using poly(Glu80Na,Tyr20) as a substrate. Maximal TPK activity required prior detergent dispersion of the membranes with 0.05% Triton X-100 and the presence of vanadate, a potent inhibitor of phosphotyrosine protein phosphatases, in the phosphorylation medium. Optimal conditions for measurement of TPK activity were 10 mM of MgCl2 and MnCl2, at 30 degrees C and pH 7.0. TPK activity was inhibited by genistein, with a IC50 value of 15 microM, while no inhibition was observed in the presence of 1-(5-isoquinolinesulfonyl)-2-methyl piperazine dihydrochloride (H7), an inhibitor of serine-threonine kinases. TPK activity was enriched 4-fold in the BBM fraction relative to cortex homogenate. It was co-enriched with BBM enzyme markers, but not with those of the basolateral membrane (BLM). The endogenous substrates of TPK in brush-border and basolateral membranes were determined by Western blot analysis using an antiphosphotyrosine monoclonal antibody (PY20). Various phosphotyrosine-containing proteins were found in the BBM (31, 34, 46, 50, 53, 72, 90, 118 and 170 kDa) and in the BLM (37, 48, 50, 53, 72, 90, 130 and 170 kDa). Addition of exogenous insulin receptor to BBM and BLM increased the phosphorylation of most of the substrates. Solubilization of the TPK activity from BBM with 0.5% CHAPS and subsequent gel filtration on Superdex 75 yielded two peaks of tyrosine protein kinase activity with apparent molecular masses of 49 and 66 kDa. These results provide evidence for a non-receptor TPK activity associated with the renal tubular luminal membrane. PMID- 1637844 TI - Chemical exchange between lamellar and non-lamellar lipid phases. A one- and two dimensional 31P-NMR study. AB - One- and two-dimensional 31P-exchange NMR has been used to investigate chemical exchange between coexisting lamellar (L alpha) and non-lamellar (hexagonal HII and cubic I2) lipid phases. Samples of DOPE, DOPE/DOPC (9:1 and 7:3), DOPE/cholesterol sulfate (9:1), DOPC/monoolein (MO) (3:7 and 1:1), and DOPC/DOPE/cholesterol (1:1:2) were macroscopically oriented on glass plates and studied at the 0 degree orientation (angle between the bilayer normal and the external magnetic field), where the L alpha, HII, and I2 resonances are resolved. A reversible L alpha to HII transition was observed for all of the samples except for the DOPC/MO mixtures, which displayed a reversible L alpha to I2 transition. Near-equilibrium mixtures of L alpha and either HII or I2 were obtained after prolonged incubation at a given temperature. Two-dimensional exchange experiments were performed on DOPE at 9-14 degrees C for mixing times ranging from 500 ms to 2 s. For all samples, one-dimensional exchange experiments were performed for mixing times ranging from 100 ms to 4 s, at temperatures ranging from 3 degrees C to 73 degrees C. No evidence of lipid exchange between lamellar and non-lamellar phases was observed, indicating that if such a process occurs it is either very slow on the seconds' timescale, or involves an undetectable quantity of lipid. The results place constraints on the stability or kinetic behaviour of proposed transition intermediates (Siegel, D.P. (1986) Biophys. J. 49, 1155-1170). PMID- 1637845 TI - Citrate as an aluminum chelator and positive effector of the sodium efflux in single barnacle muscle fibers. AB - The injection of citrate produces considerably greater stimulation of the Na efflux in ouabain-poisoned fibers (from the barnacle Balanus nubilus) than in unpoisoned fibers. When injected in excess together with Al into unpoisoned fibers it is without effect. Its injection is also without effect on the decline in the Na efflux elicited by injecting Al beforehand. Citrate injection into ouabain-poisoned fibers following peak stimulation by injecting Al produces a further rise which is a function of the Al concentration. Al injection after peak stimulation of the ouabain-insensitive Na efflux by citrate is usually without significant effect. Injection of aspartate into poisoned fibers causes a small rise in the remaining Na efflux and fails to prevent the response to Al injection from occurring. Taken together, these observations are in keeping with the view that citrate is not only a powerful chelator of Al but also a powerful activator of reverse Na+/Ca2+ exchange in ouabain-poisoned fibers, presumably because of its ability to raise myoplasmic pMg. PMID- 1637846 TI - Levitation, holding, and rotation of cells within traps made by high-frequency fields. AB - Biological cells and other particles can be electrically manipulated by means of negative dielectrophoresis within microchambers whose electrode geometry is of the order of the cell size. Very-high-frequency fields (50 MHz and above) and media of increased relative permittivity are especially suitable for the purpose, as shown by experimental data on levitation and rotation. It appears to be possible to move and rotate cells or particles at will using this technology. PMID- 1637847 TI - Membrane-structuring properties of bacterial long-chain alkylresorcinols. AB - To investigate the mechanism by which 5-n-alkyl(C19-C25)-resorcinols synthesized by certain bacteria of the Azotobacter genus affect the lipid bilayers of cellular membranes, planar bimolecular membranes were formed from these alkyl resorcinols and from mixtures of those and typical bacterial phospholipids such as phosphatidylethanolamine, phosphatidylglycerol, and diphosphatidylglycerol. The electrical properties and, in some instances, the stability of the prepared membranes have been studied. The alkylresorcinols have been found to associate with phospholipids to form oligomeric and polymeric complexes, thereby giving rise to modifications in the bilayer structure and properties. It has been shown that the same compounds suppress the mitochondrial respiration in the presence of NAD-dependent substrates, but they activate it if succinate is used as substrate. This fact is explained in terms of the interaction between the alkylresorcinols and membrane phospholipids. PMID- 1637848 TI - Generation and characterization of iron- and barium-loaded liposomes. AB - Previous work (Veiro and Cullis (1990) Biochim. Biophys. Acta 1025, 109-115) has shown that Ca2+ can be accumulated into large unilamellar vesicles (LUVs) in the presence of a transmembrane pH gradient (inside acidic) and the Ca(2+)-ionophore A23187. Here, the ability of A23187 to mediate the uptake of iron and barium into LUVs has been investigated. It is shown that under appropriate conditions of temperature and A23187 concentration, iron (in the form of Fe2+) can be accumulated into EPC and DSPC/cholesterol (55:45; mol/mol) LUVs with an acidic interior. This uptake is dependent on the internal buffer concentration, with maximum levels of uptake in the range of 300 nmol of cation per mumol lipid. The DSPC-cholesterol LUV systems exhibit superior retention properties compared to the EPC systems. It is demonstrated that Ba2+ can also be loaded by similar methods. It is also shown that the maximally loaded Fe(2+)- and Ba(2+)-containing LUVs exhibit increased densities. This is expressed by enhanced gravimetric properties, as an increased proportion of the loaded LUVs can be pelleted by low speed centrifugation, and by enhanced electron densities, in that the Ba(2+) loaded systems can be directly visualized employing cryo-electron microscopy. PMID- 1637849 TI - Lipid microsphere containing lipophilic heme: preparation and oxygen transportation under physiological conditions. AB - Lipophilic heme (1-laurylimidazole-ligated 5,10,15,20-tetrakis(alpha, alpha, alpha, alpha-o- pivalamidophenyl)porphinatoiron(II) complex) is solubilized in lipid (triglyceride) at high concentrations and emulsified with a phospholipid in physiological salt solution, giving a deeply red-colored suspension of lipid microspheres (approx. 250 nm in diameter). The heme forms an oxygen adduct in a similar manner as oxyhemoglobin and the lipid microspheres take up and release oxygen reversibly at 37 degrees C in the aqueous medium. The oxygen-transporting ability is comparable with that of the red blood cell. Intravenous injection of the heme/lipid microsphere solution to rabbits demonstrates that it transports oxygen even in vivo and that it is cleared from the blood stream with a half-life time of approx. 1 h. PMID- 1637851 TI - Lipids and lipid metabolism. PMID- 1637850 TI - Some negatively charged phospholipid derivatives prolong the liposome circulation in vivo. AB - A series of negatively charged phospholipid derivatives has been synthesized by coupling aliphatic dicarboxylic acids, HOOC(CH2)nCOOH, to dioleoylphosphatidylethanolamine (DOPE). The individual derivatives were incorporated into egg phosphatidylcholine/cholesterol liposomes (2:1, molar ratio) and injected into mice to test its effect on liposome circulation in vivo. The effectiveness of DOPE derivatives was dependent on the hydrocarbon chain length between the terminal carboxyl group and the amide bond. N-Glutaryl DOPE and N-adipyl DOPE were effective in prolonging the circulation time of liposomes. On the other hand, liposome uptake by the liver and spleen was increased by the addition of N-malonyl DOPE or N-succinyl DOPE, while it was not changed by the addition of N-pimelyl DOPE and N-suberyl DOPE. Our observation suggested that not all negatively charged phospholipids enhance liposome uptake by RES, some even reduce the uptake. PMID- 1637852 TI - Dietary supplementation with coenzyme Q10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoprotein to the initiation of lipid peroxidation. AB - Ubiquinol-10 (CoQH2, the reduced form of coenzyme Q10) is a potent antioxidant present in human low-density lipoprotein (LDL). Supplementation of humans with ubiquinone-10 (CoQ, the oxidized coenzyme) increased the concentrations of CoQH2 in plasma and in all of its lipoproteins. Intake of a single oral dose of 100 or 200 mg CoQ increased the total plasma coenzyme content by 80 or 150%, respectively, within 6 h. Long-term supplementation (three times 100 mg CoQ/day) resulted in 4-fold enrichment of CoQH2 in plasma and LDL with the latter containing 2.8 CoQH2 molecules per LDL particle (on day 11). Approx. 80% of the coenzyme was present as CoQH2 and the CoQH2/CoQ ratio was unaffected by supplementation, indicating that the redox state of coenzyme Q10 is tightly controlled in the blood. Oxidation of LDL containing various [CoQH2] by a mild, steady flux of aqueous peroxyl radicals resulted immediately in very slow formation of lipid hydroperoxides. However, in each case the rate of lipid oxidation increased markedly with the disappearance of 80-90% CoQH2. Moreover, the cumulative radical dose required to reach this 'break point' in lipid oxidation was proportional to the amount of CoQH2 incorporated in vivo into the LDL. Thus, oral supplementation with CoQ increases CoQH2 in the plasma and all lipoproteins thereby increasing the resistance of LDL to radical oxidation. PMID- 1637853 TI - Tumor accumulation of novel RES-avoiding liposomes. AB - For passive targeting of liposomes to tumor tissues, we earlier developed reticuloendothelial system (RES)-avoiding liposomes modified with a uronic acid derivative, palmityl-D-glucuronide (PGlcUA) (Namba, Y., Sakakibara, T., Masada, M., Ito, F. and Oku, N. (1990) Chem. Pharm. Bull. 38, 1663-1666). In this present study, we examined the blood clearance and biodistribution of PGlcUA-liposomes (dipalmitoylphosphatidylcholine/cholesterol/PGlcUA = 40:40:20 as a molar ratio) in normal and tumor-bearing mice. Liposomes containing dipalmitoylphosphatidylglycerol (DPPG) instead of PGlcUA was also examined as a control. When [3H]inulin-encapsulated PGlcUA-liposomes and DPPG-liposomes were intravenously injected into normal mice, approx. 50% of the 3H radioactivity was recovered from the liver, the bulk of RES, at 12 h after administration of DPPG liposomes, while only approx. 20% of it was found there when PGlcUA-liposomes were administered. Radioactivity remaining in the plasma at 12 h after injection was 5-fold higher when PGlcUA-liposomes were injected than when DPPG-liposomes were used. Biodistribution of liposomes in tumor-bearing mice was also examined. Mice were inoculated with 10(7) S180 cells into the hind leg. After 1 week, liposomes were injected. Radioactivity of [3H]inulin originally encapsulated in the PGlcUA-liposomes accumulated in the tumor to an extent 3-4-fold higher than that of the marker in DPPG-liposomes. Liver/tumor ratio of the radioactivity was 12 for DPPG-liposomes and only 2 for PGlcUA-liposomes. This latter value is the lowest of various liposome formulations ever reported. PMID- 1637854 TI - Biosynthesis of prostaglandins from 17(18)epoxy-eicosatetraenoic acid, a cytochrome P-450 metabolite of eicosapentaenoic acid. AB - Eicosapentaenoic acid (20:5(n - 3)) is oxygenated to 17S(18R)epoxyeicosatetraenoic acid (EpETE) by microsomes of monkey seminal vesicles, which also are rich in prostaglandin (PG) H synthase. The metabolism of racemic [14C]17(18)EpETE by PGH synthase of sheep vesicular glands was investigated in the present report. The two main metabolites were identified by GC-MS as 17(18)epoxyprostagland E2 (17(18)EpPGE2) and 17(18)EpPGF2 alpha. The structures were confirmed by chemical synthesis of these prostaglandins from PGE3. 17(18)EpPGE1 was synthesized from 17,18-dehydro-PGE1 by the same method. Alkali treatment of 17(18)EpPGE2 yielded 17(18)EpPGB2, which could be resolved by RP-HPLC into the 17R(18S) and 17S(18R) stereoisomers. The 17S(18R) stereoisomer was identified by co-chromatography with [14C]17S(18R)EpPGB2, which was formed by PGH synthase from biosynthetic [14C]17S(18R)EpETE. The 17(18)epoxyprostaglandins were found to be relatively unstable during acidic extractive isolation. 17(18)EpPGE1 and 17(18)EpPGE2 could not be detected in seminal vesicles of the cynomolgus monkey in significant amounts relative to 19-hydroxy-PGE1. Nevertheless, biosynthesis of 17(18)epoxyprostaglandins should be considered when the biological effects of 17S(18R)EpETE are investigated. PMID- 1637855 TI - Cultured oligodendrocytes metabolize a fluorescent analogue of sulphatide; inhibition by monensin. AB - It has been suggested that oligodendrocytes can actively phagocytose myelin debris during active myelination or after injury and experimental demyelination. Therefore, we have used a fluorescent analogue (N-lissamine rhodaminyl-(12 aminododecanoyl) cerebroside 3-sulphate) to study the metabolic fate of sulphatide, a galactosphingolipid that is highly enriched in myelin membranes. The fluorescent sulphatide was incorporated in small unilamellar vesicles and administered to cultured oligodendrocytes. The association of the lipid probe to the cells in culture was saturable in time and with the concentration of the probe. The processes of association, internalization and subcellular distribution were followed by confocal scanning laser microscopy and appeared to be very rapid. Within 20 min a marked perinuclear staining was seen. After prolonged incubation the fluorescence distributed gradually over the cytoplasm and into cellular branches along structures suggestive of cytoskeletal elements. Lipid analysis demonstrated that ceramide was the major metabolite present in the cells but galactosylceramide, sphingomyelin and free fatty acid were also detected. In the culture medium only free fatty acid and sphingomyelin were found. Monensin did not affect the cellular association and internalization of the fluorescent sulphatide but markedly reduced its conversion to metabolic products. These results indicate that exogenous sulphatide is targeted to the Golgi apparatus prior to its lysosomal degradation. PMID- 1637856 TI - Possible influence of lysophospholipase on the production of 1-acyl-2 acetylglycerophosphocholine in macrophages. AB - The rate of production of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) and 1-acyl-2-acetyl-sn-glycero-3-phosphocholine (acylPAF) was measured in macrophages following the incorporation of [3H]acetate. Upon activation by A23187, guinea pig alveolar macrophages incorporated [3H]acetate into PAF, but a little radioactivity was found in acylPAF. However, labeling of acylPAF and PAF with [3H]acetate was greatly enhanced in A23187-stimulated alveolar macrophages that had been pretreated with phenylmethanesulphonyl fluoride (PMSF). [3H]PAF was predominantly converted to 1-[3H]alkyl-2-acyl glycerophosphocholine, but [14C]acylPAF rapidly hydrolyzed to 14C-labeled free fatty acid by the incubation with lysates prepared from macrophages. The deacetylation of [14C]acylPAF and [3H]PAF by acetylhydrolase and also the hydrolysis of [14C]lysoPC by lysophospholipase were strongly inhibited in macrophages that had been pretreated with PMSF, while PMSF failed to inhibit the activities of acetyltransferase and acyltransferase. The relative proportions of PAF and acylPAF were quite different in different types of cells. In contrast to alveolar macrophages, peritoneal macrophages, neutrophils and spleen cells from guinea pigs incorporated 2-4 times more [3H]acetate into acylPAF than into PAF. The presence of high levels of acylPAF in peritoneal macrophages was confirmed by GLC-MS analysis. The activities of lysophospholipase, acetylhydrolase and acetyltransferase were measured in alveolar and peritoneal macrophages to determine whether the preferential formation of acylPAF as compared to PAF in peritoneal macrophages was due to differences in these activities between alveolar and peritoneal macrophages. The activity of acetylhydrolase of peritoneal macrophages was almost the same as that in alveolar macrophages. The activity of acetyltransferase in peritoneal macrophages was about half of that in alveolar macrophages. However, the activity of lysophospholipase in peritoneal macrophages was one-sixth of that in alveolar macrophages. These results suggest that lysophospholipase is one of the primary factors involved in the control of the production of acylPAF in activated cells, and that it acts by modulating the availability of lysoPC for the synthesis of acylPAF. Furthermore, high levels of activity of lysophospholipase allow the preferential formation of PAF, via the rapid hydrolysis of lysoPC which would act as a competitive inhibitor of the incorporation of acetate into lysoPAF. PMID- 1637857 TI - Modulation of sphingomyelinase-induced cholesterol esterification in fibroblasts, CaCo2 cells, macrophages and smooth muscle cells. AB - The present study has focused on three questions concerning the effect of sphingomyelinase on release of free cholesterol from the plasma membrane and its intracellular translocation: (i) Can one change the direction of the flow of cholesterol? (ii) Can one modulate the flow? (iii) May such a mechanism be relevant in atherogenesis? (i) The results obtained show that even in the presence of potent nonlipoprotein cholesterol acceptors in the medium, the intracellular flow of cholesterol is not reduced as measured by cholesterol esterification. Moreover, in sphingomyelinase-treated cells, cholesterol efflux in presence of nonlipoprotein acceptors was not enhanced even when intracellular esterification was inhibited. (ii) Modulation of the sphingomyelinase induced cholesterol flow can be obtained by 100 microM verapamil which reduces it. In human skin fibroblast, interference with the delivery of free cholesterol to its site of esterification was found in the presence of brefeldin A. (iii) Aortic smooth muscle cells in culture are sensitive to low concentrations of sphingomyelinase and the increase in esterified cholesterol is evident also after exposure to the enzyme for 24 h. The present results suggest that in the plasma membrane, free cholesterol bound to sphingomyelin may be in a compartment which renders it more available for transport to the cell interior than for efflux. In view of the sensitivity of aortic smooth muscle cells to sphingomyelinase, this mechanism for enhanced esterification of cholesterol could be relevant to the transformation of arterial smooth muscle cells into foam cells in the process of atherogenesis. PMID- 1637858 TI - Distribution of alkyl and alkenyl ether-linked phospholipids and platelet activating factor-like lipid in various species of invertebrates. AB - The levels of alkenylacyl, alkylacyl and diacyl subclasses of choline glycerophospholipid (CGP) and ethanolamine glycerophospholipid (EGP) fractions in 28 species of various invertebrates were studied. We found that only small amounts of either 1-alkyl-2-acyl-sn-glycero-3-phosphocholine (alkylacyl-GPC) or 1 alkenyl-2-acyl-sn-glycero-3-phosphoethanolamine (alkenylacyl-GPE) are present in most species of insects. On the other hand, almost all species examined in various phyla other than Arthropoda were shown to contain large amounts of both alkylacyl-GPC and alkenylacyl-GPE. The highest proportion of alkylacyl subclass in CGP was noted in sponge, Halichondria japonica (81.8% of CGP) and the highest proportion of alkenylacyl subclass in EGP was found in clam worm, Marphysa sanguinea (88.7% of EGP). We next surveyed the presence of platelet-activating factor (PAF)-like lipid in 45 species of invertebrates. PAF-like lipid was widely distributed among various lower animals. The highest value was obtained for sea cucumber, Stichopus japonicus, in which PAF-like lipid was present throughout the body. We also confirmed the presence of acetyltransferase activity in several lower animals. These results suggest that alkyl and alkenyl ether-linked phospholipids including PAF are physiologically important molecules particularly for invertebrates belonging to lower phyla. PMID- 1637859 TI - Diacylglycerol metabolism in neonatal rat liver: characterization of cytosolic diacylglycerol lipase activity and its activation by monoalkylglycerols. AB - Diacylglycerol lipase (glycerol ester hydrolase, EC 3.1.1.3) activities were investigated in subcellular fractions from neonatal and adult rat liver in order to determine whether one or more different lipases might provide the substrate for the developmentally expressed, activity monoacylglycerol acyltransferase. The assay for diacylglycerol lipase examined the hydrolysis of sn-1-stearoyl,2- [14C]oleoylglycerol to labeled monoacylglycerol and fatty acid. Highest specific activities were found in lysosomes (pH 4.8) and cytosol and microsomes (pH 8). The specific activity from plasma membrane from adult liver was 5.8-fold higher than the corresponding activity in the neonate. In other fractions, however, no developmental differences were observed in activity or distribution. In both lysosomes and cytosol, 75 to 90% of the labeled product was monoacylglycerol, suggesting that these fractions contained relatively little monoacylglycerol lipase activity. In contrast, 80% of the labeled product from microsomes was fatty acid, suggesting the presence of monoacylglycerol lipase in this fraction. Analysis of the reaction products strongly suggested that the lysosomal and cytosolic diacylglycerol lipase activities hydrolyzed the acyl-group at the sn-1 position. The effects of serum and NaCl on diacylglycerol lipase from each of the subcellular fractions differed from those effects routinely observed on lipoprotein lipase and hepatic lipase, suggesting that the hepatic diacylglycerol lipase activities were not second functions of these triacylglycerol lipases. Cytosolic diacylglycerol lipase activity from neonatal liver and adult liver was characterized. The apparent Km for 1-stearoyl,2-oleoylglycerol was 115 microM. There was no preference for a diacylglycerol with arachidonate in the sn-2 position. Bovine serum albumin stimulated the activity, whereas dithiothreitol, N ethylmaleimide, and ATP inhibited the activity. Both sn-1(3)- and 2 monooleylglycerol ethers stimulated cytosolic diacylglycerol lipase activity 2-3 fold. The corresponding amide analogs stimulated 28 to 85%, monooleoylglycerol itself had little effect, and 1-alkyl- or 1-acyl-lysophosphatidylcholine inhibited the activity. These data provide the first characterization of hepatic subcellular lipase activities from neonatal and adult rat liver and suggest that independent diacylglycerol and monoacylglycerol lipase activities are present in microsomal membranes and that the microsomal and cytosolic diacylglycerol lipase activities may describe an ambipathic enzyme. The data also suggest possible cellular regulation by monoalkylglycerols. PMID- 1637860 TI - Ribosomal proteins from Thermus thermophilus for structural investigations. AB - In parallel with crystallographic studies of ribosomes from Thermus thermophilus, a long-term program on the crystallization and structural investigations of ribosomal proteins from the same microorganism has been started at the Institute of Protein Research (Pushchino, Russia). At present, more than half of the individual ribosomal proteins from T thermophilus have been purified without denaturating agents on a preparative scale and some of them have been obtained in the crystalline form. X-ray structural analysis of two ribosomal proteins, L1 and S6, is being carried out jointly with the Institute of Molecular Biology (Moscow, Russia) and laboratory of professor A Liljas (Lund University, Sweden). L1 is the large protein of the large ribosomal subunit. It can bind not only to a specific site on the 23S rRNA, but also to the mRNA that codes for L1 and L11, thereby acting as a translational repressor for the synthesis of these proteins. The crystals of L1 are orthorhombic and diffract to about 2 A resolution. Native data and data for several heavy atom derivatives have been collected. S6 is a small acidic protein from the small ribosomal subunit. The crystals of S6 are orthorhombic and diffract to 2 A resolution. Native data and derivatives' data have been collected. PMID- 1637861 TI - Recognition of correct reading frame by the ribosome. AB - The translation frame-monitoring mechanism has been suggested earlier, based on transient complementary contacts, between mRNA and rRNA. Recent studies related to the frame-monitoring mechanism are reviewed. The mechanism is well supported by both new experimental and sequence analysis data. Experiments are suggested for further elucidation of the structural details of the mRNA-rRNA interaction in the ribosome. PMID- 1637862 TI - Functional topography of human ribosomes as studied by affinity labeling with reactive mRNA analogs. AB - Derivatives of 5'-32P labeled (pU)3 an (pU)6 bearing 4-(N-2-chloroethyl-N methylamino)benzylmethylamine residue attached to 5'-phosphate via phosphamide bond and (Up)5U[32P]pC and (Up)11U[32P]pC bearing 4-(N-2-chloroethyl-N methylamino)benzyl residue attached to 3'-end via benzylidene bond were applied for the affinity labeling of 80S ribosomes from human placenta in the presence of a cognate tRNA. The derivatives of 32P-labeled pAUG and pAUGU3 analogous to the 5'-phosphamides of (pU)n were used for affinity labeling of 40S subunits in the presence of ternary complex eIF-2.GTP.Met-tRNA(f). The sites of the reagents' attachment to 18S ribosomal RNA were identified by blot-hybridization of the modified 18S rRNA with restriction fragments of the corresponding rDNA. They were found to be located within positions 976-1057 for (pU)6 and pAUGU3 derivatives and within 976-1164 for (pU)3 and pAUG ones. The sites of 18S rRNA modification with the derivatives of (Up)5UpC and (Up)11UpC were found within positions 1610 1869 at 3'-end of the molecule. All the sites identified here are located presumably within highly conserved parts of the eukaryotic small subunit rRNA secondary structure. PMID- 1637863 TI - Photochemical cross-linking of the anticodon loop of yeast tRNA(Phe) to 30S subunit protein S7 at the ribosomal A and P sites. AB - Yeast tRNA(Phe), containing the photoreactive nucleoside 2-azidoadenosine at position 37 within the anticodon loop, has been cross-linked to the aminoacyl tRNA (A) and peptidyl-tRNA (P) binding sites of the Escherichia coli ribosome. The 30S subunit was exclusively labeled in each case, and cross-linking occurred to both protein and 16S rRNA. Electrophoretic and immunological analyses demonstrated that S7 was the only 30S-subunit protein covalently attached to the tRNA. However, digestion of the A and P site-labeled S7 with trypsin revealed a unique pattern of cross-linked peptide(s) at each site. Thus, while the anticodon loop of tRNA is in close proximity to protein S7 at both the A and P sites, it neighbors a different portion of the protein molecule in each. The placement of the aminoacyl- and peptidyl-tRNA binding sites is discussed in relationship to recent models of the 30S ribosomal subunit. PMID- 1637864 TI - Ribosome function determined by fluorescence. AB - Five different fluorescence phenomena are considered in relation to their use to study the structure and function of ribosomes. These are: quantum yield or emission intensity; emission wavelength maximum; fluorescence anisotropy; collisional quenching; and nonradiative energy transfer. Results from a number of studies in which these techniques were used are described and summarized in relation to the movement and conformation of tRNA, the nascent peptide, and mRNA in a ribosome during the reaction steps of peptide elongation. PMID- 1637865 TI - The two main states of the elongating ribosome and the role of the alpha-sarcin stem-loop structure of 23S RNA. AB - According to the allosteric three-site model of the elongation cycle the ribosome oscillates between two main-functional states, viz the pre-translocational state with occupied A and P sites (E site with low affinity) and the post translocational state with occupied P and E sites (A site with low affinity). This proposition could be confirmed by a determination of the thermodynamic parameters. High activation-energy barriers were found between both states, namely about 90 kJ mol-1 at 15 mM Mg2+ for either transition (post----pre transition = A-site binding and pre----post transition = translocation). The various A-site states (binding of ternary complex, EF-Tu dependent GTP cleavage, peptide-bond formation) are not separated by significant activation-energy barriers. The rate-limiting step of the elongation cycle is A-site binding, and not translocation as assumed previously. The principal role of both elongation factors is the reduction of the respective activation-energy barrier, thus accelerating the rate of the elongation cycle by several orders of magnitude. Cleavage of a single phosphodiester bond after G2661 of 23S rRNA by the RNase alpha-sarcin abolishes the functions of both elongation factors on the ribosome. This observation implies that the alpha-sarcin stem-loop structure plays an important role in the ribosomal conformational changes involved in the allosteric transitions. Indeed we could demonstrate that suitable oligodeoxynucleotide probes complementary to the alpha-sarcin region induce a conformational change in the 50S subunits; this conformational change causes an irreversible dissociation of tightly coupled ribosomes upon sucrose-gradient centrifugation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637866 TI - Novel data on interactions of elongation factor Ts. AB - Interactions of EF-Ts with EF-Tu at all steps of the elongation cycle were studied by limited trypsinolysis, gel-filtration, analytical centrifugation and fluorescence polarization techniques. It is shown that EF-Ts does not dissociate from EF-Tu after GDP to GTP exchange, but remains bound to the Aa-tRNA.EF-Tu.GTP complex up to GTP hydrolysis stage on the ribosome. The possible role of these interactions is discussed. PMID- 1637867 TI - Binding of ATP and messenger RNA by the beta-subunit of eukaryotic initiation factor 2. AB - In addition to forming a ternary complex with Met-tRNA(f) and GTP, eukaryotic initiation factor 2 (eIF-2) recognizes a specific site in mRNA molecules. Both binding activities are regulated by ATP, which itself binds tightly and specifically to eIF-2. Denaturation of eIF-2 with urea leads to complete loss of Met-tRNA(f) binding activity, while mRNA binding activity is stable. Hence, distinct conformational features in eIF-2 are required for ternary complex formation and for binding of mRNA. Chromatography of eIF-2 over ATP-agarose, in denaturing conditions that induce polypeptide subunit dissociation, results in selective retention of the beta-subunit of eIF-2. Isolated beta-subunit is capable of binding mRNA as well as ATP. Cibacron blue 3G-A binds tightly to eIF-2 and inhibits the binding of mRNA. This inhibition is relieved upon addition of ATP, showing that Cibacron blue 3G-A competes with ATP for eIF-2. eIF-2 beta subunit, active in binding of mRNA, is recovered upon chromatography of eIF-2 in denaturing conditions over matrix-bound Cibacron blue 3G-A. These results show that the ability of eIF-2 to bind mRNA and its ability to bind ATP are both lodged within remarkably stable domains of its beta-subunit. During initiation of protein synthesis, the eIF-2 beta subunit may thus interact with three ligands important for translational control: Met-tRNA(f), mRNA and ATP. PMID- 1637868 TI - Cell-free translation systems from different eukaryotes differ in their sensitivity to a template sugar-phosphate backbone. AB - To study the role of a messenger sugar-phosphate backbone in the ribosomal decoding process, poly(U) and poly(dT) template activity in different eukaryotic systems has been compared. 80S ribosomes from Saccharomyces cerevisiae appeared to be able to translate poly(dT) both in the presence and in the absence of elongation factors, contrary to poly(U). However, ribosomes from higher eukaryotes (wheat germ, rabbit liver) are completely inefficient in poly(dT) translation. Moreover, rabbit liver ribosomes fail to bind effectively phenylalanyl-tRNA in the presence of poly(dT) although the polynucleotide seems to interact with the ribosomal decoding center. It is also of particular interest that hybrid ribosomes formed from the yeast and rabbit liver subunits can translate poly(dT) only when the large ribosomal subunit from yeast is used. PMID- 1637869 TI - Interaction of yeast tRNA(Phe) anticodon arm with 40S ribosomal subunit of rabbit liver. AB - The 15-nucleotide analog of yeast tRNA(Phe) anticodon arm binds cooperatively to two sites of poly(U) programmed 40S ribosome like intact tRNA(Phe). The cooperativity coefficients appeared to be about 4 for tRNA(Phe) and 50 for its anticodon arm. Anticodon arm contributes the majority of free energy of tRNA binding to a programmed 40S ribosomal subunit. The correct codon-anticodon pairing seems to play the key role in the cooperativity origin. Contrary to the anticodon arm template independent binding of the whole tRNA to the small ribosomal subunit is revealed. PMID- 1637870 TI - Interaction of wheat germ translation initiation factor 2 with GDP and GTP. AB - The wheat germ translation initiation factor 2 (WGeIF-2) was isolated in a homogeneous state by an efficient procedure and characterized. Its molecular mass, as determined by a gel-filtration method is approximately 150,000 Da. According to SDS-PAGE WGeIF-2 consists of four subunits with M(r) 37,000 (alpha), 40,000 (beta), 42,000 (gamma) and 52,000 (delta). The beta- and gamma-subunits (but not the alpha-subunit) of WGeIF-2 can be readily phosphorylated by the double-stranded RNA activated kinase isolated from rabbit reticulocytes. Dissociation constants for WGeIF-2 complexes with GDP and GTP were measured. In our evaluation the WGeIF-2 affinity for GDP (KdGDP = 1.5 x 10(-7) M) was only 10 times higher than for GTP (KdGTP = 1.5 x 10(-6) M), while for rabbit reticulocyte eIF-2 (RReIF-2) the difference has been estimated as as much as two orders of magnitude in accordance with the literature. Close values of dissociation constants for WGeIF-2 complexes with guanine nucleotides suggest that at a sufficiently high [GTP]/[GDP] ratio the nucleotide exchange in wheat cells may take place without the participation of specific factor (eIF-2B) which catalyzes the nucleotide exchange on eIF-2 from mammalian cells. PMID- 1637871 TI - Conservative system for dosage-dependent modulation of translational fidelity in eukaryotes. AB - Variations in dosage of some genes can alter the level of translational fidelity. The Saccharomyces cerevisiae genes that act as dosage-dependent suppressors and/or modulators of suppression, are the following: some tRNA genes (for example, tRNA(Gln)) inducing readthrough by mispairing; genes coding for either translational elongation factor or other proteins taking part in translation; and some genes of unknown function. We suggest that the SUP35 protein is a factor which may play a major role in balance-dependent regulation of translational fidelity. Homologues of this genes have been identified in other yeast genera (Pichia), green algae (Chlamydomonas) and various animals including man. No homologies have been found in the polychaeta (Nereis) or in insects (Drosophila). Rates of evolution differ for two separate parts of the genes; the N-terminal part, which is important for ambiguous translation in Saccharomyces, is markedly variable in the organisms tested. However, the C-terminal part which is required for yeast viability has a common origin but a separate evolution from that of the EF-Tu protein family. PMID- 1637872 TI - Interaction of protein synthesis initiation factors with the mRNA cap structure. AB - The mechanism of mRNA recognition by proteins interacting with the mRNA cap structure was investigated by photochemical cross-linking of proteins with 32P labelled reoviral RNAs. Using ribosomal washes as a source of eukaryotic protein synthesis initiation factors, we identified the well-known cap binding proteins eIF-4B and -4E, but eIF-2 and eIF-3 as well. The interplay of purified eIF-4A, 4B, and -4F was studied in relation to ATP dependence and cap analogue sensitivity of cap binding. Next to their well-known roles in the initiation process, eIF-2 and eIF-3 also cross-linked to the 5' cap. eIF-2 stimulated eIF-4B and -4E cross-linking, an observation that has been previously described more extensively. The interaction of eIF-2 with the 5' end of mRNA was extremely sensitive to K(+)-ions and was resistant to a high concentration of Mg(2+)-ions; this influence of mono- and divalent ions was in contrast with the cross-linking of eIF-4B and -4E. Optimal interaction of these factors was obtained at moderate K+ concentration and low Mg(2+)-ion concentrations. eIF-2 cross-linking was sensitive to high protein to mRNA ratios indicating a weak affinity as compared to eIF-4E and -4B. The interaction of eIF-3 with the cap of mRNA is also weak as it was counteracted by all other cap binding proteins, leading to an inability to detect the cross-linking of this protein in crude eIF preparations. Time kinetics of formation of complexes suggested eIF-2 to be one of the first factors to interact with mRNA. Preformed RNA-protein complexes were dissociated after cap analogue addition, suggesting reversible interactions between RNA and proteins. PMID- 1637873 TI - Role of cytoplasmic mRNP proteins in translation. AB - Polyribosomal and free mRNPs from rabbit reticulocytes were isolated and characterized. Translation of mRNPs was studied in the rabbit reticulocyte and wheat germ cell-free systems. Both classes of mRNPs were active in rabbit reticulocyte lysates. However, considerable differences between mRNPs and mRNA have been revealed. High concentrations of mRNA in the form of mRNP did not inhibit protein biosynthesis, whereas the same amounts of deproteinized mRNA caused inhibition of this process. Polyribosomal mRNPs and deproteinized mRNA, but not free mRNPs, are active in the wheat germ cell-free translation system. Translation of free mRNPs in this system can be restored by addition of 0.5 M KCl wash of rabbit reticulocyte ribosomes. These results suggest the existence of a special repressor/activator regulatory system which controls mRNA distribution between free mRNPs and polyribosomes in rabbit reticulocytes. This regulatory system should include: i) a translation repressor associated with mRNA within free mRNPs, preventing its translation; and ii) a translation activator associated with ribosomes, overcoming the effect of the repressor. Both classes of cytoplasmic mRNPs contain a major 50 kDa protein (p50). The content of this protein per mol of mRNA in free mRNPs is twice as much as in polyribosomal ones. The method of p50 isolation has been developed and some properties of this protein were investigated. It has been shown that small amounts of p50 stimulate, whereas high amounts inhibit mRNA translation. We suggest that p50 has a dual role in protein biosynthesis. In polyribosomal mRNPs (p50:mRNA approximately 2:1, mol/mol), this protein promotes the translation process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637874 TI - Structural consensus of RNA templates replicated by Q beta replicase. AB - Q beta replicase replicates a variety of enzyme-specific small RNAs in addition to the phage genomic RNA. The sequence analysis has revealed that all these RNAs are potentially capable of forming a consensus secondary structure element. It represents a stalk which is formed by the 5'-GGG ... and ... CCCA-3' complementary stretches at the termini of the replicating RNA molecules and adjacent 5'- and 3'-hairpins, which may form a stacking with the stalk. The structure found is rather similar to the analogous structure in the tRNA molecule. The genomic RNA of the Q beta phage and other related phages can also form a similar structural element. PMID- 1637875 TI - Regulation of transcription by translational components in coupled translation transcription cell-free system. AB - A coupled translation-transcription cell-free system was established from eukaryotic cells. The biosynthetic activity of this coupled system closely resembles the synthetic behavior of cells in vivo, and exhibits regulatory phenomena similar to that of intact cells. The translational system consists of rabbit reticulocyte lysate, or its components fractionated by centrifugation. The transcriptional portion consists of cockerel liver nuclei. Incorporation of amino acids into protein by the coupled system is linear for hours. Similarly, transcription in the coupled system is continuous for hours and is proportional with time. More than 90% of the transcriptional products are secreted into the incubation medium. The components of the translational system influence and regulate transcriptional activities. In the presence of ribosomes the nuclei transcribe mostly poly(A)+ RNA with alpha-amanitin sensitivity consistent with activation of RNA polymerase II. Hybrid selection experiments demonstrate authentic preproalbumin mRNA among the transcriptional products. The putative mRNA secreted into the medium in the coupled system is found on polysomes, indicating translation of de novo synthesized message. Addition of excess reticulocyte mRNP to the medium of the coupled system results in transcription of primarily ribosomal RNA, 5S RNA, and tRNA, the products of RNA polymerases I and III. These activities closely imitate the behavior of liver in vivo under conditions of nutritional shifts or hormonal influences. The coupled system transcribes, processes, and transports substantial quantities of RNA, about 1.6 micrograms/10(6) nuclei/h. Thus, a coupled system has been established that lends itself to the exploration of regulatory interactions of cell components as it appears to closely resemble the in vivo situation. PMID- 1637876 TI - Enzymatic biosynthesis of cyclosporin A and analogues. AB - The final assembly of the undecapeptide chain of cyclosporin A and its cyclization is accomplished in Beauveria nivea by cyclosporin synthetase. This multienzyme is the largest integrated enzyme structure so far reported. Its size has been estimated at approximately 1,400 kDa by two different methods: 1), by 3% SDS-PAGE using the related multienzymes ACV synthetase and gramicidin S synthetase 2 as references (420 and 556 kDa, respectively); and 2), by CsCl density gradient centrifugation experiments using fluorescence-labeled cyclosporin synthetase. Besides cyclosporin A and a number of cyclosporins known from fermentation studies cyclosporin synthetase is capable of synthesizing some new cyclosporins which are so far unobtainable by fermentation. So, for example the synthesis of [N-methyl-(+)-2-amino-3-hydroxy-4,4-dimethyloctanoic acid1]CyA, dihydro-CyA, [L-norvaline2,5, N-methyl-L-norvaline11]CyA, [L-allo-isoleucine5, N methyl-L-allo-isoleucine11]CyA, [D-2-aminobutyric acid8]CyA, [beta-chloro-D alanine8]CyA and some related compounds could be established. By using a related but different enzyme from Cylindrotrichum Bonorden, the peptolide [L-threonine2, L-leucine5,10, D-2-hydroxyisovaleric acid8]CyA could be synthesized in vitro. We were able to synthesize these cyclosporins in sufficient quantities to examine their structure by FAB mass spectroscopy and explore their immunosuppressivity. It was found that all new cyclosporins so far synthesized in the in vitro system are immunosuppressive. PMID- 1637877 TI - Graft-versus-leukemia activity after bone marrow transplantation does not require graft-versus-host disease. AB - Clinical data have suggested that graft-versus-host disease (GVHD) plays a crucial role in the antileukemic effects of bone marrow grafts. We investigated (a) whether bone marrow cells unable to induce GVHD can effect graft-versus leukemia (GVL) activity and (b) whether such antileukemic capacity depends on the presence of T lymphocytes in the graft. Balb/c mice were inoculated with A20 cells, a B-cell lymphoma/leukemia of Balb/c origin. Four weeks after tumor inoculation the animals were lethally irradiated and received a bone marrow graft. Cells from (Balb/c x C57) F1 or (C3H x Balb/c) F1 hybrids were transplanted into parental-strain Balb/c mice. Since lymphocytes from F1 hybrids are unable to cause graft-versus-host reactivity against a parental-strain animal, we used this experimental setting to explore GVL effects in a GVHD-free system. In vitro incubation with monoclonal anti-Thy-1.2 antibody plus complement was used to eliminate Thy-1+ cells. After syngeneic transplantation, the death rate due to leukemia remained unchanged (91%) compared with that among untreated animals (86%). Following transplantation of F1 marrow cells of either (C57 x Balb/c) F1 or (C3H x Balb/c) F1 origin, death rates of 40% and 50% were observed; these were significantly lower. Depletion of Thy 1+ cells from bone marrow graft caused only a slight increase in the leukemic death rate after transplantation of bone marrow of (C57 x Balb/c) F1 hybrid origin (50%), but a high leukemic death rate was seen after transplantation of (C3H x Balb/c) F1 bone marrow (100%). Additional experiments with fully allogeneic, T-cell-depleted C57 bone marrow transplantation suggest an antileukemic effect that is comparable to that seen after transplantation of unmanipulated F1 bone marrow. Taken together, our results indicate that GVL activity can be dissociated from graft-versus-host reaction. PMID- 1637878 TI - Prevention of viridans-group streptococcal septicemia in oncohematologic patients: a controlled comparative study on the effect of penicillin G and cotrimoxazole. AB - In a controlled randomized study among 48 patients undergoing 75 courses of aggressive antileukemic therapy, it was shown that cotrimoxazole was less effective than penicillin G in preventing septicemia due to viridans streptococci. Both antibiotics were given intravenously. During 35 episodes of chemotherapy in the group of patients on penicillin G only, one patient developed a streptococcal bacteremia; this contrasted with bacteremia and septicemia in seven patients during 40 episodes in the group on cotrimoxazole. In three of these seven patients, septicemia was associated with respiratory failure and it was the cause of death in one. Both aerobic gram-negative rods and streptococci which caused infection despite cotrimoxazole prophylaxis were resistant to cotrimoxazole. Side effects such as hypersensitivity and favorable or unfavorable interaction with the oral selective decontamination regimen were similar for the two drugs, with the exception of colonization with Candida spp, which occurred more often in patients on cotrimoxazole than in patients on penicillin. PMID- 1637879 TI - A simple elimination of clonogenic tumor cells from human bone marrow in vitro by heat: its application to autologous bone marrow transplantation for B-cell lymphoma. AB - The application of hyperthermia to the treatment of neoplastic disease has focused on solid tumors. Since the hyperthermic sensitivity of human B-cell lymphoma cells is not known, we have examined the effect of hyperthermia on the growth of B-cell lymphoma cell lines (Raji and Daudi) in vitro to evaluate the ability to purge tumor cells from normal bone marrow by heat, utilizing a limiting-dilution assay to measure log depletion of tumor cells in a 20-fold excess of normal bone marrow. When exposed at 42 degrees C and 43 degrees C for 120 min, both clonogenic Raji and Daudi cells were dramatically decreased (a 4- to 6-log reduction) with exposure time, while leaving over half of the normal granulocyte-macrophage progenitor cells surviving at 42 degrees C and 10% at 43 degrees C. This high level of lymphoma-cell depletion by heat correlated with that obtained in immunologic and pharmacologic studies. These results suggest that in vitro hyperthermia might be applied effectively for the elimination of residual lymphoma cells in autologous marrow grafts before autologous bone marrow transplantation in B-cell non-Hodgkin's lymphoma. PMID- 1637880 TI - Retinoic acid in the treatment of acute promyelocytic leukemia: inefficacy of the 13-cis isomer and induction of complete remission by the all-trans isomer complicated by thromboembolic events. AB - The clinical course of three patients with acute promyelocytic leukemia receiving all-trans retinoic acid (ATRA) as a single agent is reported. The first two patients were in first and second relapse of their leukemia that had occurred despite maintenance treatment with 13-cis retinoic acid after chemotherapy induced complete remission (CR). A switch to ATRA was followed by achievement of a CR in two patients. The third patient received ATRA as first-line therapy. Two patients experienced thromboembolic complications during the phase of ATRA induced leukocytosis. One of them died of pulmonary embolism on day 16 of treatment. The two responding patients who did not receive consolidation chemotherapy relapsed after 6 and 9 months, respectively. Increase of the ATRA dose failed to induce a new remission. PMID- 1637881 TI - The frequency and significance of megakaryocytic emperipolesis in myeloproliferative and reactive states. AB - Sixty-three bone marrow (BM) biopsy paraffin sections from patients with platelet counts of 1000 x 10(9)/1 or greater were examined to determine the incidence of megakaryocytic emperipolesis for the various myeloproliferative disorders (MPDs) and for reactive thrombocytosis. Of those cases classified as specific MPDs, 77% of primary thrombocythemia (PT) specimens, 100% of the polycythemia vera (PV) specimens, a single idiopathic myelofibrosis (IMF) specimen, and 17% of the chronic granulocytic leukemia (CGL) specimens demonstrated emperipolesis within megakaryocytes. Two of three cases grouped as MPDs but not further classified also demonstrated emperipolesis. Of the cases of reactive thrombocytosis (RT), 75% showed the presence of emperipolesis. Our results indicate that, with the exception of CGL, emperipolesis can be found in the BM megakaryocytes of the great majority of patients who have extreme thrombocytosis. The underlying cause, whether myeloproliferative or reactive, does not apparently influence the incidence of the phenomenon. PMID- 1637882 TI - Cold agglutinins of anti-Pr specificity in rubella embryopathy. AB - Cold agglutinins of anti-Pr specificity were detected in two newborn infants suffering from serologically ascertained rubella embryopathy, an IgM kappa anti Pr(a), titer 64, and an IgM lambda anti-Pr1, titer 16. The cases are rare examples of cold agglutinin production in newborns; a possible relationship between anti-Pr specificity and rubella infection is discussed. PMID- 1637883 TI - Erythropoietin levels in patients depositing autologous blood in short intervals. AB - Plasma immunoreactive erythropoietin (EPO) concentrations were studied in ten patients (7 men, 3 women) predonating autologous blood for hip arthroplasty. Donations were scheduled on day 1, 3, 7, 14 (and 21 if four units could not be donated previously). A predonation hemoglobin concentration of 11 g/dl was required. The donations led to a decline of the hemoglobin concentration from 14.1 +/- 1.0 g/dl (X +/- SD) prior to donation to 11.0 +/- 0.9 g/dl on day 15. EPO concentration prior to donation was 17.6 +/- 2.6 mU/ml. Each phlebotomy was followed by a rise in EPO levels that reached a peak concentration within 1 day. The highest concentration (35.8 +/- 15.0 mU/ml) was measured on day 16. The peak concentration was followed by a plateau at lower, although still elevated levels after the first and second donation, and by a slow, continuous decline after the third and fourth donation. This particular time course is similar to that during weekly donations [15]. The time integral of the EPO concentration during the first 3 weeks, however, was greater in the present study. This increased availability of EPO early during donation may lead to a more efficient stimulation of erythropoiesis. PMID- 1637885 TI - A study of von Willebrand's disease in Jordan. AB - This work reports on the results of a 9-year study of von Willebrand's disease and its subtypes in Jordan, a country with a predominantly Arab population. There were a total of 65 patients in 32 families. Detailed study of 61 patients including von Willebrand factor multimers was done for the purpose of subtyping them. Type I and variants were seen in 36 patients (59%). Type II A and variants with decreased ristocetin response accounted for seven patients (11.5%), while 11 (18%) were of type II B. The severe type (type III) accounted for seven patients (11.5%). Von Willebrand's disease was the second most commonly seen inherited bleeding disorder after hemophilia A. It is concluded that although the observed frequency of von Willebrand's disease in this study in Jordan is lower than that in Europe and the USA, the true prevalence cannot be ascertained since many of the mild cases presumably were missed because of referral patterns. Type I and its variants was the most common type found, but the observed frequency of types II B and III was more than that reported in Europeans and Americans. PMID- 1637884 TI - Histologic findings in bone marrow biopsies of patients with thrombocythemic cell counts. AB - Histologic diagnoses from bone marrow biopsies were analyzed in a total of 1165 patients presenting with thrombocythemic platelet counts at initial examination. Two cut-off points suggested by the Polycythemia Vera Study Group to define thrombocythemia by platelet counts were compared: the former limiting value of 1000 x 10(9)/l platelets versus the recently proposed value of 600 x 10(9)/l. The percentage of all nonproliferative disorders was 41% under the lower, dropping to 11% under the high cut-off point. The respective figures for myeloproliferative disorders increased from 49% under the lower to 74% under the high limiting value. Primary thrombocythemia was included in 72% by the lower, and in only 40% by the high limiting value when classified by its histologic pattern in bone marrow biopsy. A striking decrease of platelet counts occurs, related to fiber increase, among each of three main groups of myeloproliferative disorders: in CML with megakaryocytic predominance from 40% down to 25%, in megakaryocytic granulocytic myelosis (primary, i.e., agnogenic myelofibrosis) from 36.6% to 10%, and in primary thrombocythemia from 72.6% to 28.6% in cases with reticulin sclerosis. PMID- 1637886 TI - High interleukin-6 plasma levels in acute promyelocytic leukemia. PMID- 1637887 TI - Frequency and DNA sequence of tal-1 rearrangement in children with T-cell acute lymphoblastic leukemia. AB - Using nested polymerase chain reaction (PCR) a gene rearrangement named tal-1 deletion was found in five of 56 leukemic bone marrow samples from children with T-cell acute lymphoblastic leukemia (ALL). The DNA sequences of the PCR fragments consisted of the known conserved germline sequences in addition to short DNA insertions at the breakpoint region, which were different in each patient. Moreover, one patient was examined at diagnosis and at relapse 11 months later, revealing identical DNA sequences at the rearrangement site. The recombination site of the tal rearrangement therefore may be used as a genetic marker for detecting minimal residual disease in about 10% of T-cell ALL in childhood. PMID- 1637888 TI - Myocardial infarction after FEIBA therapy in a hemophilia-B patient with a factor IX inhibitor. AB - A case of myocardial infarction (MI) in a hemophilia B patient with a factor IX (FIX) inhibitor (6 BU) is described. MI occurred after two infusions of FEIBA concentrate. Unexpectedly, these infusions resulted in a neutralization of the inhibitor and a consistent plasma FIX activity which may have increased the thrombotic risks. Four days later, a psoas hematoma was suspected. At that time the inhibitor remained undetectable, allowing a therapy with purified FIX concentrates. No recurrence of thrombotic complication was observed. This is an additional illustration of the thrombotic risks associated with the use of activated prothrombin complex concentrates, especially in patients having pre existing risk factors for thrombosis. The management of bleeding episodes in hemophilia B patients with inhibitor represents an especially difficult challenge. PMID- 1637889 TI - Parvovirus B19 infection and bone marrow transplantation. AB - Parvovirus B19 lytically infects erythroid progenitor cells and thereby causes cessation of erythropoiesis in infected individuals. Anemia develops only if red cell turnover is increased, as in patients with chronic hemolysis (transient aplastic crisis). In addition to transient marrow failure, B19 can cause chronic anemia and, rarely, pancytopenia in immunodeficient patients who are not able to mount an adequate immune response to clear the virus. Bone marrow transplantation, although causing significant immunosuppression, is rarely complicated by symptomatic B19 infection. This is probably due to effective passive immunotherapy by immunoglobulin infusions immediately after transplantation and early reconstitution of antibody responses after uncomplicated transplantation. PMID- 1637890 TI - Serum beta-carotene: a mechanism or "yellow finger"? PMID- 1637891 TI - Time-related confounders and intermediate variables. PMID- 1637892 TI - Serum cholesterol, beta-carotene, and risk of lung cancer. AB - This paper hypothesizes that beta-carotene mediates the association between low serum cholesterol and increased risk of lung cancer, predicts that the association should be greater in population strata with low intake of beta carotene than in those with high intake if the hypothesis is correct, and investigates this prediction with data from a 24-year cohort study of 1,960 middle-aged employed men. In the total cohort, serum cholesterol was not related to risk of lung cancer. The relative risk associated with a difference of -1.0 mmol per liter in serum cholesterol was 1.01 (95% confidence interval of 0.80 1.27) after adjustment for cigarette smoking, age, and intake of beta-carotene. In contrast, however, when the study group was restricted to men with intake of beta-carotene less than 5,000 (N = 929) or less than 3,000 IU per day (N = 272), comparable relative risks were 1.10 and 1.21, respectively. Although the 95% confidence intervals for these relative risks were broad and included unity, the result is consistent with expectation. We conclude that the hypothesis warrants further investigation. PMID- 1637893 TI - High-fat foods and the risk of lung cancer. AB - We conducted a population-based case-control study of the association of dietary cholesterol and fat with lung cancer between 1983 and 1985 on Oahu, Hawaii. The study population included 226 men and 100 women with lung cancer, and 597 male and 268 female community controls matched for age (+/- 5 years) and sex. There was a positive dose-response relation between the consumption of processed meats (luncheon meats, bacon, sausage), dairy foods (whole milk, regular ice cream), eggs, and particular desserts (fruit pies, custard/cream pies) and the risk of lung cancer in men. We also found a positive trend in the risk of lung cancer in women with increasing intake of some processed meats (bacon, Spam) and desserts (cakes, custard/cream pies). The dose-response relation tended to be stronger among men who were heavy smokers and who were diagnosed with squamous cell cancer of the lung. A positive trend in risk was found for nitrite intake in men and dimethylnitrosamine intake in men and women. These data indicate that smokers with a high intake of foods rich in fat and animal protein or who have a preference for cured meats are at increased risk of lung cancer. PMID- 1637894 TI - Oral and pharyngeal cancer and occupation: a case-control study. AB - We studied the relation between occupation and oral and pharyngeal cancer with a population-based case-control study conducted in four areas of the United States. The study group included 1,114 incident male and female cases and 1,268 frequency matched controls. After adjustment for age, race, smoking, alcohol, and study location, an analysis of lifetime occupational histories revealed a small number of noteworthy associations. Risk was increased among male carpet installers (23 cases, 4 controls), with an adjusted odds ratio of 7.7 [95% confidence interval (CI) = 2.4-24.9], and tended to rise with longer duration of employment. A decreased risk was found among male and female textile mill workers (odds ratio 0.48, 95% CI = 0.27-0.88). Previously reported increases in oral cancer risks among printing workers, electrical and electronics workers, and workers other than carpet installers who were possibly exposed to formaldehyde were not found in this study. For several employment groups, including male machinists, primary metal industry workers, petroleum industry workers, painters, furniture and fixture industry workers, woodworking machine operators, and workers with inferred exposure to fossil fuel combustion, odds ratios were approximately 2.0 for cancers of pharyngeal sites. PMID- 1637895 TI - G-estimation of the effect of prophylaxis therapy for Pneumocystis carinii pneumonia on the survival of AIDS patients. AB - AIDS Clinical Trial Group Randomized Trial 002 compared the effect of high-dose with low-dose 3-azido-3-deoxythymidine (AZT) on the survival of AIDS patients. Embedded within the trial was an essentially uncontrolled observational study of the effect of prophylaxis therapy for pneumocystis carinii pneumonia on survival. In this paper, we estimate the causal effect of prophylaxis therapy on survival by using the method of G-estimation to estimate the parameters of a structural nested failure time model (SNFTM). Our SNFTM relates a subject's observed time of death and observed prophylaxis history to the time the subject would have died if, possibly contrary to fact, prophylaxis therapy had been withheld. We find that, under our assumptions, the data are consistent with prophylaxis therapy increasing survival by 16% or decreasing survival by 18% at the alpha = 0.05 level. The analytic approach proposed in this paper will be necessary to control bias in any epidemiologic study in which there exists a time-dependent risk factor for death, such as pneumocystis carinii pneumonia history, that (A1) influences subsequent exposure to the agent under study, for example, prophylaxis therapy, and (A2) is itself influenced by past exposure to the study agent. Conditions A1 and A2 will be true whenever there exists a time-dependent risk factor that is simultaneously a confounder and an intermediate variable. PMID- 1637896 TI - Nonsteroidal antiinflammatory drugs and gastrointestinal hospitalizations in Saskatchewan: a cohort study. AB - We evaluated the association between individual nonsteroidal antiinflammatory drugs (NSAIDs) and gastrointestinal (GI) toxicity in a retrospective cohort study aimed at examining and comparing the incidence of serious gastrointestinal disorders among NSAIDs users. We observed 2,302 GI hospitalizations among diclofenac, indomethacin, naproxen, piroxicam, sulindac, and other NSAIDs users in the province of Saskatchewan, Canada, from 1982 to 1986 for 228,392 persons who contributed 679,075 person-years of follow-up and filled close to 1.5 million NSAID prescriptions. Current NSAID users presented an increased risk of GI hospitalization [rate ratio (RR) = 3.9, 95% confidence interval = 3.5-4.4]. RRs decreased as time since the last prescription increased: 2.2 (1.9-2.6) for recent past users and 1.3 (1.1-1.5) for less recent past users. Among current users, RRs were the highest in indomethacin users (5.1, 4.3-6.0), and the lowest in sulindac users (3.1, 2.3-4.2). All of these results are adjusted for calendar time, sex, and age. Age showed a particularly strong association with the risk of GI hospitalization. PMID- 1637897 TI - Ethics, scientific validity, and the design of epidemiologic studies. AB - Ethical conflicts between moral principles and methodologic standards sometimes occur in epidemiologic research. When dilemmas are discerned, they may be analyzed using the ethical principles of beneficence, nonmaleficence, justice, and respect for the autonomy of persons. We argue that, in addition to scientific validity, the welfare and rights of research subjects should be taken into account in making decisions regarding all aspects of the design and conduct of epidemiologic studies, and that the commitment of epidemiologists to the advancement of scientific knowledge should not outweigh or override all other considerations. PMID- 1637898 TI - Geographical differences in myocardial infarction incidence in eight Swedish counties, 1976-1981. AB - Considerable regional variation in coronary heart disease mortality has been observed in Sweden. This variation is of public health concern and is also a point of departure for etiologic studies. The central aim of the present study was to investigate whether there are also regional differences in myocardial infarction incidence and to evaluate whether these are likely to be explained by regional differences in smoking, blood pressure, and serum cholesterol. The study base consisted of subjects age 30-64 living in eight Swedish counties during 1976 1981. Cases of myocardial infarction were identified using both hospital discharge and death records. A 30-40% increased incidence of myocardial infarction was found in the two northernmost counties compared with Stockholm county. The regional differences in myocardial infarction incidence were not related to differences in smoking but might be due in part to differences in serum cholesterol and blood pressure, and to socioeconomic factors as well. PMID- 1637899 TI - Reporting and selection bias in case-control studies of congenital malformations. AB - Retrospective studies of congenital malformations frequently rely on exposures reported by study subjects. Differential error in exposure reporting by cases and controls, which has alternatively been referred to as "recall bias" and "reporting bias," may result in a biased effect measure. Some authors have attempted to avoid reporting bias by comparing exposures between two malformed groups, rather than between cases and nonmalformed controls. This approach, however, may introduce its own bias, which we call selection bias. Both reporting bias and selection bias are shown to be algebraically equivalent to bias arising from exposure misclassification. The magnitudes of these biases are compared for a range of plausible parametric values. The case-control design is sensitive to both differential reporting and selection bias, and the choice of study design involves balancing these two sources of bias. PMID- 1637900 TI - Moderate maternal and paternal alcohol consumption and the risk of spontaneous abortion. AB - Maternal alcoholism can lead to the fetal alcohol syndrome in offspring, but the effect of more moderate alcohol consumption during pregnancy remains an issue of concern. Therefore, we analyzed data from a large case-control study of spontaneous abortion (626 cases, 1,300 controls) that ascertained maternal alcohol consumption before and during pregnancy, as well as paternal consumption. Asking when in pregnancy alcohol consumption changed allowed us to calculate a weighted average of the amount consumed weekly during the first trimester. The odds ratio for consumption of seven or more drinks per week was 1.9 [95% confidence interval (CI) = 1.1-3.4] when adjusted for maternal smoking, passive smoking, and maternal age. Data were too sparse to examine higher consumption levels. There was some evidence that cases may have had less opportunity than controls to decrease consumption during their shorter pregnancies, potentially biasing the odds ratio upward. The adjusted odds ratio for any paternal alcohol consumption was 1.2 (CI = 0.93-1.5), with no dose-response effect seen. Among pregnancies in which the mother did not drink, there was no association with paternal drinking. PMID- 1637901 TI - The protective effect of alcohol on the occurrence of epidemic oyster-borne hepatitis A. AB - Limited data indicate that drinking alcoholic beverages along with eating food contaminated with Shigella or Salmonella decreases the risk and/or the severity of illness. No such study has been reported following exposure to a viral pathogen. During an oyster-borne outbreak of hepatitis A, we studied the effect of ingestion of alcoholic beverages concomitant with consumption of contaminated oysters. The analysis was restricted to 51 cases and 33 controls who had consumed the implicated raw oysters. After controlling for potential confounders, we found a protective effect for beverages that have an alcohol concentration of greater than or equal to 10% (odds ratio = 0.1, 95% confidence interval = 0.02-0.9), but not for beverages with an alcohol concentration of less than 10% (odds ratio = 0.7, 95% confidence interval = 0.2-2.9). PMID- 1637902 TI - Oral contraceptive use and the risk of inflammatory bowel disease. AB - We used rosters of the Crohn's and Colitis Foundation of America to identify potential cases and peer-nominated controls to explore the reported association between oral contraceptives and inflammatory bowel disease. Overall, women who used oral contraceptives were at increased risk of developing Crohn's disease (odds ratio = 1.49, 95% confidence interval (CI) = 0.99-2.26). The findings persisted after adjustment for age at symptom onset, decade of onset, education, marital status, and location of disease. There was an interaction with cigarette smoking; the risk associated with oral contraceptives was elevated in current smokers (odds ratio = 2.64, 95% CI = 1.22-5.75), but not in former smokers or never-smokers. The risk was not elevated for ulcerative colitis (odds ratio = 1.10, 95% CI = 0.65-1.85). PMID- 1637903 TI - Validation of a method for the estimation of food portion size. AB - In the context of the planning phase of a large cohort study on dietary habits and cancer, we have developed a food frequency questionnaire on usual food intake, which includes a set of pictures to estimate the portion size of 23 different dishes. The validity of the estimation of portion size of recently consumed foods has been questioned by other researchers. To validate the use of pictures, we organized a field trial with 103 volunteers. They were invited to a dinner where standard Italian dishes were offered (total 17 foods); all of the portions they chose were recorded and weighed. The following day, we interviewed the volunteers on what they consumed during the dinner, and we compared the weight of the food actually eaten with the weight of the food represented in the pictures. The volunteers overestimated the portion size by more than 20% for six foods and underestimated the portion size by more than 20% for four foods. In addition, we found a tendency toward overestimation of portion size by those who ate smaller portions and underestimation, by those who ate larger portions ("flat slope syndrome"). PMID- 1637904 TI - Confounding of algorithmic efficiency by programming language in exact odds ratio estimation. PMID- 1637905 TI - A delicate subject. PMID- 1637906 TI - Health care reform: do we need it? Do we need it now? PMID- 1637907 TI - Advance directive. PMID- 1637908 TI - Urostomy and urinary pH. AB - Significant variations of urinary pH can cause problems for all human beings, but these problems are magnified when an individual has a urostomy. Most significant stomal and peristomal complications are related to an alkaline urine including hyperkeratosis; stoma bleeding, incrustation, and ulceration; stoma stenosis; urinary tract infection; odor; and urinary calculi. Treatment of these conditions includes both external and internal measures. External methods of treatment involve keeping urine away from the stoma and the peristomal skin by use of a correctly fitting clean appliance and a night drainage system. Vinegar solution compresses can help to restore the acid mantle of the skin. Internal methods of treatment that are advocated in the literature include ingestion of cranberry juice and ascorbic acid to promote urine acidity. Increasing oral intake of fluids is the least risky method to promote the production of acidic, dilute urine, and results are equally effective. PMID- 1637909 TI - Analgesic administration via rectum or stoma. AB - The rectal and stomal routes for administering analgesics are discussed as alternatives to invasive, parenteral routes when a patient is unable to take medication by mouth. The ET nurse has an important role in reminding members of the health care team about these routes and in teaching patients and family members (i.e., caregivers) to use them properly. PMID- 1637910 TI - Options in the surgical treatment of bladder cancer. AB - In general, bladder cancers may be divided into two classes: superficial and invasive. Superficial cancers can be treated without systemic chemotherapy or radical surgery. However, until recently, treatment of invasive cancers usually involved removal of the bladder and construction of an ileal conduit. Newer methods of treatment focus on preservation and reconstruction. In this article, surgical procedures that incorporate these goals and other treatment options, specifically chemotherapy and radiation therapy, are discussed, and the individual needs of patients are emphasized. PMID- 1637911 TI - Aspects of sexuality for patients with stomas and continent pouches. AB - An alteration in a person's body image can have an impact on sexual issues for that person. A person who has a conventional or continent diversion should receive instruction in the promotion of sexual health as a component of nursing care. ET nurses have an excellent opportunity to provide information on and direction in sexual rehabilitation for their patients. PMID- 1637912 TI - Treatment options for men with sexual dysfunction. AB - Erectile dysfunction can occur in men of any age, but it is more common in older men. It is one of the most devastating problems a man can face. An estimated 10 to 12 million American men experience impotence. Increased sexual expectations for an aging population have resulted in an increased interest in the treatment of impotence. Treatment options range from a simple adjustment in medication to surgical implantation of a penile prosthesis. The good news is that sexual function can almost always be restored. The bad news is that many men with chronic erectile dysfunction never seek help. A sensitive nurse who has an understanding of sexual health and functioning and the conditions that interfere with them can steer those who need help in the direction of treatment. PMID- 1637913 TI - Training programs for retail personnel. PMID- 1637914 TI - Regulatory update. PMID- 1637915 TI - [Regulation of the specific and nonspecific ion conductivity of mitochondria by adenine nucleotide carriers]. AB - The functioning of the adenine nucleotide carrier as a regulated pore which, depending on incubation conditions, operates as either a specific conductivity channel for H+ and K+ ions, or a nonspecific channel for low molecular weight metabolites, is reviewed. Both specific and nonspecific conductivities over this specific channel are controlled by the conformational state of the carrier protein molecule. The conformational states of the ATP/ADP-carrier alter by the specific effect of adenine nucleotides, ATP/ADP transport inhibitors, Ca2+ ions, medium tonicity, and energization of mitochondria. The transition of the ATP/ADP carrier to the conformational state characterized by nonspecific conductivity is inhibited by cyclosporin A. The roles of the adenine nucleotide carrier in the realization of effects of Ca(2+)-mobilizing hormones and glucagon during mitochondrial function are discussed. PMID- 1637916 TI - [Lipid metabolism in rat tissues during chronic gamma-irradiation and action of ubiquinone Q-9]. AB - Chronic gamma-irradiation of rats with the daily dose of 0.129 Gy activates the synthesis of various classes of lipids in the thymus, spleen and bone marrow cells and induces lipid accumulation in these tissues. Feeding of rats with the antioxidant, ubiquinone Q-9, under conditions of chronic irradiation causes a considerable normalization of lipogenesis and levels of the lipid concentration in the tissues of animals irradiated with the dose of 20 Gy. PMID- 1637917 TI - [Limited proteolysis of human albumin and immunoglobulin G by Legionella pneumophila metalloproteinase]. AB - Metalloproteinase of Legionella pneumophila is the major extracellular proteinase of this bacterial species which splits human immunoglobulin G in the hinge region to form the (Fab')2 fragment. This fragment is relatively stable and undergoes further proteolysis at a slow rate. The c' fragment is unstable and is apparently split down to fragments CH2 and CH3. The metalloproteinase splits human serum albumin down to products having lower molecular masses. Another bacterial metalloproteinase, thermolysin, produces a similar effect, although at a slower rate. PMID- 1637918 TI - [Binding of cholesterol by apolipoproteins A-I and E]. AB - It was shown that cholesterol can interact with some guanidine group-containing compounds (guanidine proper, arginine, metformine and dodecylguanidine bromide) as well as with the arginine-rich proteins--apoproteins A-1 and E. In the latter case this interaction results in the formation of cholesterol-apoprotein complexes. Analysis of such complexes revealed that one apo-A-1 molecule binds 17 22, whereas one apo-E molecule--30-35 sterol molecules, which approximately correspondence to the amount of arginine residues in these proteins. The formation of cholesterol-apoprotein complexes seems to be due to: (1) formation of hydrogen bonds and ion-dipole interactions between the hydroxyl groups of cholesterol and the guanidine groups of the apoprotein arginine residues and, presumably, the carboxylic groups of aspartic or glutamic acids, eventually resulting in the production of chelate complexes; (2) hydrophobic interaction of the cholesterol aliphatic chain with the nonpolar side chains of the amino acids occupying the third position from arginine in the protein molecule. PMID- 1637919 TI - [Reactivation and reconstitution of glutamate decarboxylase upon the interaction of its dimers with pyridoxal phosphate]. AB - The relationship between the reactivation and reconstitution of the hexameric form of glutamate decarboxylase during the interaction of inactive apoenzyme dimers with pyridoxal phosphate (PLP) has been studied. It was shown that the restoration of enzymatic activity, appearance of spectral maximum at 340 nm, and reconstitution of the hexamer depend on the amount of PLP added; this reaction is completed when the PLP concentration reaches that of the initial enzyme. This native hexamer of the holo- and apoenzyme does not practically contain exposed sulfhydryl groups. Ten cysteine residues become available after DS-Na denaturation. The dimer of the apoenzyme contains 8 exposed and 2 buried cysteine residues. The hexamer formation from the dimers is accompanied by the burying of the cysteine residues. When half of the required PLP was added, 7 cysteine residues became buried in experiments with DTNB and six in experiments with 4.4' DTDP. Further addition of PLP led to the disappearance of the exposed sulfhydryl groups. PMID- 1637920 TI - [Interaction of sex steroids with proteins from the soluble fraction of swine and cattle liver (a preliminary analysis)]. AB - The interactions of [3H]estradiol, [3H]testosterone and [3H]progesterone with soluble proteins from porcine and calf liver were studied. The specific binding of [3H]progesterone and [3H]testosterone in calf liver cytosol seems to be due to serum transcortin or its intracellular precursor (analog). Contrariwise, the specific binding of [3H]progesterone observed in porcine liver cytosol was absent in the serum. This binding was characterized by slow association and dissociation dynamics, moderate affinity for the [3H]-ligand and a high binding capacity. The structural determinants of the ligands were studied by competitive inhibition of the [3H]-ligand binding. The delta 4-3-keto group in the steroid A-ring was found to be the most important determinant. An intensive metabolism of [3H]progesterone was observed during its incubation with cytosol (data from thin-layer chromatography). A 3H-metabolite (presumably, 20 beta-dihydroprogesterone) was predominant in the bound ligand fraction. The data obtained suggest that proteins of a steromodulin type are widely distributed in the mammalian liver. PMID- 1637921 TI - [The effect of monoclonal and polyclonal antibodies to peroxidase on combined peroxidase oxidation of 4-iodophenol with luminol and 4-aminoantipyrine]. AB - The kinetics of peroxidase-dependent cooxidation for two substrate pairs [p iodophenol + 4-aminoantipyrine (AAP) and p-iodophenol + luminol was studied both in the absence and presence of polyclonal antibodies (polyAB), three types of peroxidase-specific monoclonal antibodies (monoAB) and their double or triple mixtures in a wide range of H2O2 concentrations (0.01-10.0 mM). MonoAB 2C, 3E and 9D at concentrations of 0.05-500 nM inhibited the cooxidation of p-iodophenol + AAP at H2O2 concentration above 1.0 mM but activated the cooxidation of p iodophenol + luminol. The double and triple mixtures of monoAB activated the cooxidation of p-iodophenol + AAP at the same H2O2 concentrations without any effect on the p-iodophenol + luminol cooxidation. PolyAB activated the cooxidation of p-iodophenol + AAP more effectively and only slightly activated (or inhibited) that of p-iodophenol + luminol. PolyAB diminished the values of rate constants for the interaction of the peroxidase active intermediates, E1 and E2, with p-iodophenol, AAP or luminol. Possible modes of monoAB and polyAB effects on the two substrate pair cooxidation are discussed. PMID- 1637922 TI - [A simple method of isolating monoclonal immunoglobulin M, possessing rheumatoid activity]. AB - A simple procedure for obtaining highly purified preparations of native monoclonal (Waldenstrom's disease) immunoglobulin M possessing a rheumatoid activity (IgM-RF) has been developed. The method is based on the use of affinity chromatography with a new readily available adsorbent (immunoglobulin G-porous glass) and 3 M LiCl in Tris-buffer pH 8.3-8.4 able to induce the dissociation of the IgM-RF-IgG complex. The IgM-RF preparation thus obtained was characterized in terms of amino acid composition (relative to conventional monoclonal IgM), carbohydrate composition and structure of oligosaccharide moieties of a complex type. It was shown that some dissociation conditions for the IgM-RF-IgG complex routinely used to isolate IgM-RF provoke irreversible denaturation of IgM-RF when applied to a preliminarily purified complex. PMID- 1637923 TI - [Regulation of the phospholipid turnover rate and protein kinase C activity as a necessary stage in the realization of the growth-inhibiting effect of dexamethasone on hepatoma 22 cells]. AB - The role of protein kinase C and phospholipid turnover in the realization of the cytostatic effect of dexamethasone on hormone-sensitive cells of mouse hepatoma 22 has been studied. It was found that dexamethasone added to hepatoma cells induces a rapid (within 30 min) inhibition of the protein kinase C activity with a simultaneous decrease of the 32P incorporation into the major phospholipids (phosphatidylglycerol, phosphatidylcholine, and phosphoinositides). Analysis of correlation between the protein kinase C activity and phospholipid turnover rate revealed that phosphatidylglycerol and phosphatidylcholine synthesis is under the positive control of protein kinase C, whereas that of phosphoinositides is not controlled by the enzyme. A proportional decrease in the rates of metabolism of all the three major phospholipids after addition of the hormone to hepatoma cells suggests that inhibition of phospholipid turnover is one of the primary manifestations of the dexamethasone effect. The hormone-induced decrease in the protein kinase C activity may be regarded as being due to these changes. PMID- 1637924 TI - [Functioning of latrotoxin channels during pH changes]. AB - Using the fluorescent probe BCECP, the pH dependence of Ca2+ transport in synaptosomes along alpha-latrotoxin-formed channels, was studied. It was found that the pH value in synaptosomes is equivalent to 7.16 +/- 0.09. Acidification or alkalinization of the intracellular medium by 0.1-0.3 pH units had no appreciable influence on the Ca2+ influx along latrotoxin-formed channels. Alteration of external pH caused a parallel shift in the cytoplasmic pH in the synaptosomes. The pH decrease in the external medium down to 6.0 caused the inhibition of Ca2+ fluxes along latrotoxin-formed channels. Dissipation of the proton gradient by high concentrations of KCl in the presence of nigericin decreased the latrotoxin ability to form ionic channels without any loss in the activity of the preformed channels. The influx of bivalent cations along latrotoxin-formed channels led to alkalinization of the synaptosomal cytoplasm to pH of the external medium. This pH change did not depend on the presence of Na+ in the external medium and was blocked by cadmium. PMID- 1637925 TI - [Bimodal effect of exogenous hydrogen peroxide on human neutrophils: cytotoxic effect and modulation of respiratory burst in response to an agonist]. AB - It has been found that high concentrations of exogenous hydrogen peroxide kill human neutrophils, the range of toxic concentrations being 100 times as high as that for human endothelial cells. Whereas the H2O2 doses of 30-100 mM induce a fast massive death of neutrophils, 10 mM hydrogen peroxide induces appreciable death only within several hours after treatment. H2O2 used at 30 mM decreases superoxide anion generation by neutrophils stimulated with PMA or FMLP. This decrease is commensurate in value with cell death, thus indicating a high functional resistance of survived cells. In the dose of 10 mM hydrogen peroxide potentiates FMLP (but not PMA-)-induced generation of superoxide anions. Augmentation of superoxide anion generation by H2O2-primed neutrophils in response to FMLP amounts to 200% of the control value. Hydrogen peroxide alone is incapable of inducing superoxide anion generation. It is concluded that exogenous oxidants can alter the functional activity of leukocytes freshly recruited in inflammatory and ischemic tissues. PMID- 1637927 TI - Conditioned fear and psychological trauma. PMID- 1637926 TI - [Study of the structure-activity features of lactate dehydrogenase isoenzymes using antipeptide antibodies to the M4-isoform of swine lactate dehydrogenase]. AB - The structure-function peculiarities of human, porcine, rabbit, and rat lactate dehydrogenase (LDH) isoenzymes have been studied using antipeptide antibodies (AB) against the M4-isoform of porcine LDH. Antipeptide AB were raised against the hypervariable (40% homology) N-terminal fragment (residues 1-32), and the highly conservative fragment 180-214 containing histidine in the enzyme active center. Whereas antipeptide AB against the fragment of the active center of porcine LDH M4-isoform selectively inhibited the catalytic activities of LDH isoenzymes from various sources, antipeptide AB directed against the N-end were without effect. The ability of antipeptide AB to specifically interact with various isoforms of LDH suggests that sequences 1-32 and 180-214 are immunochemically identical only in the case of human and porcine M4 isoenzymes; the relatedness of the amino acid sequence to the common antigenic determinant required the absence in the given sequence of essential amino acid substituents. Chemical modification of porcine M4-isoform by diethylpyrocarbonate and the use of specific AB revealed that histidine-195 located in the active center of LDH is not directly involved in the binding to AB. PMID- 1637928 TI - Aging of core and optional sleep. AB - Two consecutive 24-hr ambulatory recordings of 14 healthy elderly persons (7 women, 7 men, ages 88-102) and of 19 healthy young adults (10 women, 9 men, ages 25-35) were evaluated. In addition to the classical sleep parameter analysis, sleep structure was also analyzed in terms of a proposed distinction between "core" and "optional" sleep (Horne 1989). Core sleep is the essential part of the sleep and is mainly slow wave sleep. This type of sleep is composed of stages 3 and 4 on non-REM sleep (NREM 3-4). Core sleep is obtained during the first three sleep cycles and the remainder of the night sleep is considered optional sleep. Optional sleep is more altered than core sleep. However, in both optional and core sleep, NREM sleep and REM are reduced. There is also an increase in drowsiness and in the time spent awake after sleep onset; however, the extent of these effects are more obvious in elderly men. Aging effects of slow wave sleep probably represent an amplification of the changes as observed in awake electroencephalic (EEG) patterns in healthy seniors. The decrease in slow wave sleep (stages NREM 3-4) is gender related and prevails in elderly men. REM sleep diminishes with increasing age. In the elderly, most REM sleep occurs at the beginning of the night. This contrasts to younger persons where the duration of REM sleep is longer at the end of the night. Furthermore, a decrease in REM sleep latency is particularly obvious in elderly men and probably secondary to the curtailment of slow wave sleep. The ultradian NREM-REM cycle rhythm (as defined by the periodic occurrence of REM sleep) shows a monophasic trend suggesting a diminished adaptive function of aged sleep. The informative value of true, continuous ambulatory recordings in the assessment of sleep-wakefulness patterns in normal and pathological aging is stressed. PMID- 1637929 TI - Decreased (3H) quinuclidinyl benzilate binding to lymphocytes in Gilles de la Tourette syndrome. AB - In spite of an unknown pathophysiology, it has been suggested that central dopaminergic hyperactivity exists in Gilles de la Tourette syndrome (TS). Cholinergic influences have also been postulated as a dopaminergic-cholinergic balance seems to be important in other movement disorders. If TS is due to alterations of cholinergic activity, this may also be expressed at postsynaptic levels. Recently, we showed that circulating lymphocytes may serve as useful peripheral markers reflecting induced alterations or inherent changes in muscarinic receptors in the central nervous system (CNS). In the present study, we compared the muscarinic binding characteristics in peripheral lymphocytes as measured by (3H) quinuclidinyl benzilate [(3H)-QNB] in 27 unmedicated TS patients, against 22 healthy (age and gender-matched) controls. B(max) and Kd values were determined using Lineweaver-Burke plots. The mean B(max) values in nontreated TS patients was markedly and significantly lower than in controls (10.59 +/- 8.4 versus 40.16 +/- 9.2 fmole/10(6) cells, p less than 10(-6), while Kd values were similar in both groups. Our findings suggest that changes in cholinergic receptors may play a role in the pathophysiology of Tourette syndrome. PMID- 1637930 TI - Immunity, major depression, and panic disorder comorbidity. AB - Because recent research reports indicated clinical and biological differences in major depression with and without comorbid Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) panic disorder, and as altered immune measures were reported in selected subgroups of depressive patients, we investigated 51 pairs of major depressive episode (MDE) subjects, and gender- and age-matched healthy controls in order to determine if T lymphocytes number and function abnormalities were associated with Panic Disorder comorbidty. We found that those MDE subjects with DSM-III-R panic disorder (PD) had greater numbers of T cells (p less than 0.05) and PHA mitogen (p less than 0.05) responses than depressive patients without PD, as well as increased phytohemagglutinin (PHA) (p less than 0.05) concanavalin A (ConA) (p less than 0.02) mitogen responses compared to their controls. These data suggest that panic disorder comorbidity significantly contributes to the variance of immunologic parameters in major depression and has to be carefully assessed within psychoimmunological studies of psychiatric patients with affective disorders. PMID- 1637931 TI - Attentional asymmetry in schizophrenia: controlled and automatic processes. AB - Two versions of Posner's covert orienting task were administered to 14 drug-free schizophrenic patients and 12 normal controls. In the schizophrenic subjects, automatic orienting to exogenous cues in the right visual field was impaired. However, this lateralizing general deficit was not present when the schizophrenics were able to direct attention effortfully in the second version of the task using endogenous cues. These findings support the hypothesis that there is a deficit in left hemispheric mechanisms mediating visual spatial attention in schizophrenia. However, when schizophrenics are given the opportunity to use an attentional strategy they are able to partially overcome this lateralized processing deficit. PMID- 1637932 TI - Impaired recognition of affect in facial expression in depressed patients. AB - Measures of recognition of seven affects in facial and verbal expressions to 17 depressed patients and 31 controls were administered. Depressed patients were significantly impaired in the recognition of affect in the facial, but not verbal, expressions. Among the seven affects examined, depressed patients made significantly or near significantly fewer correct matches for sad, happy, and interested face items. The performance of the depressed patients was similar to that observed by Kolb and Taylor in patients with right, but not left, hemisphere cortical excisions. The neurobiology of facial recognition is reviewed, and the relevance of the observed perceptual deficit in depressed patients to the pathophysiology and symptomatology of depression is discussed. PMID- 1637933 TI - Third-ventricle enlargement and neuropsychological deficit in schizophrenia. AB - Cerebral ventricular enlargement is present in a substantial subgroup of schizophrenic patients. Most, but not all studies examining neuropsychological performance and ventricular size in schizophrenics show more severe cognitive impairment in those patients with greatest ventricular enlargement. Inconsistencies in this literature have been attributed to different neuroimaging techniques, variation in patient characteristics across studies, and the variety of neuropsychological batteries used. In the present study, schizophrenic patients (n = 49 men, n = 23 women) and normal controls (n = 13 men, n = 18 women) underwent magnetic resonance (MR) imaging of the brain and extensive neuropsychological testing including measures of frontal and temporal lobe function. A complete coronal set of MR images was used to calculate volumetric estimates of lateral and third cerebral ventricles. Highly significant associations were found between cognitive deficits and third-ventricle volume, with measures of frontal functioning, attention, and concentration showing the most robust correlations. In contrast, neuropsychological performance was not highly associated with lateral ventricular size. These findings further support the pathophysiological relevance of ventricular enlargement in schizophrenia. More specifically, third, but not lateral, ventricular enlargement was associated with greater cognitive disturbance in this sample. Results are consistent with pathological involvement of periventricular diencephalic structures resulting in dysfunctional frontal and limbic processing in a subgroup of patients. PMID- 1637934 TI - Somatostatin-like immunoreactivity in CSF in schizophrenic patients during haloperidol treatment. PMID- 1637935 TI - Seasonality in atypical depression. PMID- 1637936 TI - Early antipsychotic response to resumption of neuroleptics in drug-free chronic schizophrenic patients. PMID- 1637937 TI - The influence of beta-endorphin on testicular endocrine function in adult rats. AB - The role of beta-endorphin in testicular steroidogenesis is poorly understood. To address this issue, we treated adult hypophysectomized rats intratesticularly with either saline-50% polyvinylpyrrolidone (SAL-PVP) or human beta-endorphin (0.5 microgram/testis; a total of 1 microgram/rat/day) in SAL-PVP for 3 days. Testicular injections were made under ether anesthesia. On Day 3, rats also received injections (s.c.) of either SAL-PVP or 5 micrograms beta-endorphin in SAL-PVP to minimize the dilution of ether in the testis. One hour later, rats were treated (i.p.) with either saline or ovine LH (25 micrograms/rat). One hour after saline or LH injection, blood was obtained via heart puncture for determination of plasma progesterone (P), androstenedione (A-dione), and testosterone (T) levels. The effects of beta-endorphin (50 ng, equivalent to 13.9 pM; or 250 ng, equivalent to 69.6 pM) on P and androgen secretions in vitro were also examined. Intratesticular injections of beta-endorphin significantly (p less than 0.025) decreased the T response to LH treatment, but failed to affect plasma P and A-dione levels. Response of P to LH treatment was increased (p less than 0.005) in medium containing testicular fragments exposed to 250 ng (69.6 pM) beta endorphin. However, beta-endorphin attenuated LH effects on A-dione and T production in vitro. These studies demonstrate that beta-endorphin inhibits T secretion, possibly because of its effect on the synthesis of T precursors. Thus, testicular beta-endorphin modulates the endocrine function of the testis in adult rats. PMID- 1637938 TI - Purification and microsequencing of the intra-acrosomal protein SP-10. Evidence that SP-10 heterogeneity results from endoproteolytic processes. AB - The human sperm antigen SP-10 has been shown to be a testis-specific, intra acrosomal protein that is associated with the membranes and matrix of the acrosomal vesicle. Sperm extracts, analyzed on Western blots with a monoclonal antibody to SP-10, have shown heterogeneity of SP-10 peptides ranging from 17.5 34 kDa. Although the entire SP-10 amino acid sequence of 265 amino acids (28.3 kDa) has been deduced from sequencing SP-10 cDNAs, the nature of multiple SP-10 peptide bands is incompletely understood. In this study, we developed a three step purification method for SP-10 peptides using monoclonal antibody affinity chromatography, reverse-phase HPLC, and preparative gel electrophoresis. Eight SP 10 peptides separated by this protocol and sequenced using Edman degradation showed amino termini that corresponded to regions on the deduced SP-10 amino acid sequence. Peptides with progressively lower apparent mass aligned further toward the carboxy terminus. On the basis of putative cleavage sites on the SP-10 sequence, endoproteases that act at five different peptide bonds are predicted to cleave SP-10: these hydrolyze following arginine (a trypsin-like protease, possibly acrosin), and following serine, proline, glycine, and glutamic acid (previously undescribed intra-acrosomal protease specificities). The present studies 1) provide a purification method for SP-10 peptides; 2) confirm that the SP-10 cDNAs previously sequenced encode authentic SP-10; and 3) yield indirect evidence that endoproteases act to contribute to SP-10 heterogeneity. PMID- 1637939 TI - Protein kinase C mediates gonadotropin-releasing hormone agonist-induced meiotic maturation of follicle-enclosed rabbit oocytes. AB - The present study was undertaken to determine the effects of a protein kinase C inhibitor, staurosporine, on gonadotropin-releasing hormone agonist (GnRHa) induced oocyte maturation and follicular prostaglandin (PG) production, and the response to direct activators of protein kinase C using rabbit mature follicle culture. Treatment of mature follicles with GnRHa (buserelin and leuprolide acetate) neither stimulated nor inhibited cAMP accumulation in both the follicle and oocyte. Exposure to staurosporine at 10(-6) M 60 or 15 min before GnRHa (buserelin) administration reduced significantly the meiotic maturation of follicle-enclosed oocytes induced by GnRHa at 10(-7) M. However, staurosporine addition coincident with the agonist or thereafter did not inhibit meiotic maturation. Staurosporine suppressed GnRHa-induced meiotic maturation in a dose dependent manner, whereas hCG-stimulated oocyte maturation was not inhibited. Similarly, staurosporine administered 60 min before exposure to GnRHa suppressed GnRHa-stimulated PG production by mature follicles. The active phorbol esters, 10(-6) M 12-0-tetra-decanoyl phorbol 13-acetate (TPA) and 10(-6) M 4 beta-phorbol 12,13-didecanoate (4 beta-PDD) stimulated meiotic maturation whereas the biological inactive isomer, 4 alpha-PDD, did not. The kinetics of germinal versicle breakdown of follicle-enclosed oocytes in the presence of active phorbol esters paralleled that of GnRHa-treated oocytes. Furthermore, the concomitant addition of staurosporine at 10(-6) M to the culture medium inhibited significantly (p less than 0.05) TPA-induced meiotic maturation. These data demonstrate that GnRHa stimulated both the meiotic maturation of follicle enclosed oocytes and follicular PG formation via a mechanism other than the cAMP mediated process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637940 TI - Identification and content of insulin-like growth factors in porcine oviductal fluid. AB - Oviductal fluid (OvF) was collected from gilts by indwelling catheters during the estrous cycle and analyzed for content of insulin-like growth factors (IGF-I, IGF II). Group 1, composed of 9 gilts in a summer environment near a boar, yielded mean daily fluid volumes of 1.18 +/- 0.16 ml during estrus and 0.69 +/- 0.03 ml post-estrus. Group 2, composed of 7 gilts in a moderate-temperature, light regulated room, yielded 1.20 +/- 0.18 ml during estrus and then OvF flow essentially stopped. Serum samples were also collected 2 times daily during the cycle and analyzed along with the OvF for IGF-I and IGF-II. Serum was also analyzed for estradiol-17 beta (E2). For group 1, OvF content (concentration x fluid volume) of IGF-I and IGF-II was greater (p less than 0.05) at estrus than pre- and post-estrus. Daily mean content values (ng/day) for IGF-I and IGF-II during peri-estrus were 30.9 +/- 6.3 and 62.2 +/- 12.3, respectively. During nonestrus, values were 6.8 +/- 6.3 and 11.7 +/- 12.3, respectively. For group 2, OvF content of IGF-I and IGF-II during estrus was similar to that of group 1. Whereas IGF content differed between estrus and nonestrus periods, IGF concentrations were similar (p greater than 0.05), a finding that results from the difference in OvF produced. Compared with OvF concentrations of IGF for a given pig, blood plasma concentrations of IGF-I and IGF-II were 2- to 5-fold higher in the plasma sample collected the same day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637941 TI - Controlled vaginal delivery of antibodies in the mouse. AB - Controlled delivery of monoclonal antibodies to the mucus secretions of the vagina might provide women with passive immunoprotection against both sexually transmitted diseases and unwanted pregnancy. We have developed intravaginal devices composed of poly(ethylene-co-vinyl acetate) (EVAc) that continuously release IgG antibodies for over 30 days into buffered saline, and we have tested these devices in the vagina of mice. Polymeric devices containing either BSA (as a test reagent for proteins) or anti-hCG antibody, when inserted into the vaginas of mice, provided a continuous supply of either BSA or hCG-binding antibodies to the vaginal mucus for 30 days. Antibodies released by the devices achieved high concentration in the mucus within the lumen of the vagina, but did not significantly ascend into the uterine horns, as determined by epifluorescence microscopy of fluorescently labeled mouse IgG and by immunohistochemical localization of rabbit IgG. Our results suggest that long-term intravaginal delivery of functionally intact antibodies can be achieved with devices composed of EVAc. PMID- 1637942 TI - Tumor necrosis factor-alpha messenger ribonucleic acid and protein in human endometrium. AB - Although previous studies have shown that the tumor necrosis factor-alpha (TNF) gene is expressed in pregnancy decidua, it has not been determined whether this gene is transcribed or translated in the endometrium prior to implantation. To address this question and to identify cells expressing the TNF gene, samples of normal cycling human endometria were tested for TNF mRNA by in situ hybridization using a biotinylated antisense RNA probe, and the corresponding protein was localized in the same tissues by immunocytochemistry with a monoclonal antibody to TNF. Both TNF message and protein were identified in the endometrium throughout the menstrual cycle, and the same types of cells that contained transcripts also contained protein. As judged by the intensities of the hybridization signals, TNF mRNA increased during the proliferative phases, declined in the early secretory phase, and again rose during mid-to-late secretory phases, suggesting positive associations with levels of female sex hormones that show similar cyclic fluctuations. At the initiation of the cycle, transcripts were primarily localized to glandular epithelial cells whereas by the midproliferative phase, message was also present in stromal cells. Hybridization signals were consistently more intense in functionalis-region than in basalis region stromal cells, and were frequently stronger in basalis-region glandular epithelia than in functionalis-region glands. These observations document that the TNF gene is expressed in normal cycling endometria, suggest that ovarian hormones may regulate TNF gene transcription, and identify differences in specific endometrial compartments. The findings are also consistent with the postulate that TNF is a local mediator of cellular communications in the human endometrium. PMID- 1637943 TI - Immunocytochemical localization and messenger ribonucleic acid levels of a progesterone-dependent endometrial secretory protein (cathepsin L) in the pregnant cat uterus. AB - The purpose of this study was to localize immunocytochemically a progesterone dependent protein (PDP) and to determine PDP mRNA levels during the initial stage of the implantation period. Uterine tissue was collected from Day 0-18 postcoital animals. The tissue was processed for immunocytochemical localization of PDP, and the endometrial RNA was isolated and analyzed for PDP gene expression by slot blot hybridization. PDP was detected immunocytochemically as early as Day 5 postcoitus in the epithelial cells of the deep uterine glands, and the intensity of immunostaining appeared to peak by Day 12 postcoitus. PDP was absent in the endometrium obtained from implantation sites after Day 16 postcoitus, but the synthesis of PDP was maintained in the endometrium obtained from nonimplantation sites. Immunogold electron microscopy demonstrated that PDP was present in electron-dense granules of the glandular epithelial cells. PDP mRNA was detectable in the endometrium at Day 5 postcoitus and peaked around Day 10 postcoitus. PDP mRNA was absent in the endometrium from implantation sites after Day 16 postcoitus, but was maintained in the endometrium from nonimplantation sites. In summary, the results of this study illustrate that PDP is synthesized within the epithelial cells of the deep uterine glands, packaged within membrane bound secretory granules, and released into the uterine lumen. Also, the process of implantation alters the gene expression in a very localized way since PDP mRNA and PDP-positive granules were absent in the endometrial glands obtained from the implantation site within 1-2 days of the onset of implantation, whereas both PDP mRNA and PDP-positive granules were maintained in the endometrial glands from nonimplantation-site regions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637944 TI - Genes regulating testis size. AB - The studies described here provide information about the genetic and morphological bases for the significant differences in testis size among three closely related C57BL mouse substrains: C57BL/6J, C57BL/6ByJ, and C57BL/10J. C57BL/6J mice have normal-size testes while the other two substrains have small size testes. Genes controlling testis size are postulated to be among the estimated forty genes that differ between the C57BL/6J and C57BL/6ByJ substrains. The number of genes involved in testis size regulation was examined using recombinant inbred mouse strains. An investigation of the role of Y chromosome genes was performed by completing molecular analyses with a mouse Y chromosome specific probe. Sertoli and germ cell counts provided insight into the morphological basis for the different testis sizes. The experimental results suggest that there are at least two autosomal testis-size genes and that they control testis size by regulating the number of Sertoli cells. PMID- 1637945 TI - The effects of mate removal on pregnancy success in prairie voles (Microtus ochrogaster) and meadow voles (Microtus pennsylvanicus). AB - The effects of removing the stud male have not been controlled in many studies relating pregnancy block to the presence of an unfamiliar male. We examined the effects of removing the male on pregnancy success in prairie voles and meadow voles, two species that differ in degree of paternal investment. Whereas prairie vole males provide extensive care to offspring and accelerate pup development, meadow vole males display little or no care and delay development of pups. We predicted that removal of the stud male would decrease pregnancy success in prairie voles and either have no effect or increase success in meadow voles. In experiment 1, females were in male-induced estrus, and their mates were either left with them or were removed 4 h, 1 day, 2 days, or 8 days after mating. In experiment 2, females were in postpartum estrus, and their mates were either left with them or were removed 1 day, 2 days, or 8 days after birth of their first litter. Removal of the male soon after mating in postpartum estrus decreased pregnancy success in prairie voles and increased success in meadow voles. Thus, although removal of the stud male influenced litter production, the direction of the effect varied with species. PMID- 1637947 TI - Transcriptional expression of a testis-specific variant of the mouse pyruvate dehydrogenase E1 alpha subunit. AB - An isogene of the E1 alpha subunit of the mouse pyruvate dehydrogenase complex was shown in a previous study to map to chromosome 19. Here we demonstrate using Northern blot analysis that this gene is expressed in a testis-specific fashion. Two testis-specific E1 alpha transcripts were detected: (1) a 2.0-kb transcript that is abundant in pachytene cells but also detectable during earlier stages of spermatogenesis, and (2) a shorter 1.7-kb transcript detectable only in round spermatids. Analysis of both transcripts following RNase H digestion revealed that the smaller message is not derived from the shortening of the poly(A) tail and most likely results from the alternate use of two polyadenylation signals. Finally, analysis of polysomes isolated from 20- and 80-day-old mouse testes demonstrated that the 2.0-kb transcript is associated with the polysomal fraction, suggesting that this message is transcribed and actively translated at the same time. We conclude from these results that expression of the testis specific E1 alpha is initially expressed during the meiotic prophase stage of spermatogenesis and not under any apparent post-transcriptional regulation. PMID- 1637946 TI - Comparison of histone H1 kinase activity during meiotic maturation between two types of porcine oocytes matured in different media in vitro. AB - Histone H1 kinase (H1K) activity was assayed during meiotic maturation in porcine oocytes matured in a modified Krebs-Ringer bicarbonate solution (KRB) or in porcine follicular fluid (pFF) in vitro. Oocytes matured in KRB displayed lower male pronucleus formation ability, delayed first polar body emission, and a higher spontaneous activation rate than oocytes matured in pFF. In oocytes matured in pFF, H1K activity was low at the germinal vesicle stage and increased about 8-fold at first and second metaphases, with a transient depression at first anaphase and telophase. The H1K activity at second metaphase in oocytes matured in KRB was significantly lower than that in oocytes matured in pFF. These results suggest that the maturation medium used influences the fluctuation pattern of H1K activity and the biological characteristics of porcine oocytes cultured in vitro. PMID- 1637948 TI - Platelet-activating factor mediates phosphatidylcholine hydrolysis by phospholipase D in human endometrium. AB - Human preimplantation embryos and endometrium secrete platelet-activating factor (PAF). The mechanism of phosphatidylcholine (PC) degradation stimulated by PAF was investigated in endometrial explants prelabeled with [methyl-3H]choline or preincubated with [3H]butan-1-ol. Analysis of the water-soluble metabolites of PAF-induced PC hydrolysis in secretory endometrium demonstrated that the stimulated generation of [3H]choline ([3H]Cho) precedes that of [3H]choline phosphate ([3H]ChoP) and [3H]glycerophosphocholine ([3H]GPC). Within 30 sec there was a rapid rise in PAF-induced [3H]Cho generation and by 2 min this had increased to 59.9% +/- 10.6% (p less than 0.02), with no effect upon [3H]ChoP and [3H]GPC during this period. Both [3H]GPC and [3H]ChoP, however, were increased at a later time point. The slower [3H]ChoP generation may suggest that PC-specific phospholipase C activation as well as delayed [3H]GPC rise may be due to PC specific phospholipase A2 and lysophospholipase activation. Phospholipase D activity was confirmed by the incorporation of high-specific-activity [3H]butan-1 ol into [3H]phosphatidylbutanol ([3H]PBut). The rapid generation of [3H]PBut, which paralleled the rise in intracellular [3H]Cho, strongly suggests that PC breakdown is catalyzed by the phospholipase D pathway. It is proposed that PAF induces PC hydrolysis as a consequence of an early phospholipase D-catalyzed breakdown of PC in human secretory endometrium. This may be an alternative source for prostaglandin synthesis and an important pathway essential for long-term activation of local cellular events at the time of implantation. PMID- 1637949 TI - Timing of birth in Syrian hamsters. AB - The effects of mating time and of LD cycles on the timing of birth and length of gestation were examined in Syrian hamsters (Mesocricetus auratus). Hamsters maintained on 14L:10D cycles were mated for 2 h either in the evening or in the morning, and groups of hamsters mated in the morning were subjected to either a 6 h advance shift or a 6-h delay shift of the LD cycle on Days 5-14 of gestation. For the last 2 days of gestation the hamsters were kept in constant dim light and observed every hour to determine the time of birth. Hamsters mated in the evening gave birth an average of 4.8 h before those mated in the morning, and the hamsters subjected to an advance shift gave birth an average of 8.1 h before those subjected to delay shift. The results show that 80-100% of births occur during the subjective day on Day 16 of gestation and that the minimum duration of gestation is 15 days and 2 h. The regulation of birth appears to involve two processes, an interval timer related to the time of conception and a circadian rhythm that is governed by the LD cycle. PMID- 1637950 TI - Photoperiodic regulation of pulsatile luteinizing hormone secretion and adenohypophyseal gene expression in female golden hamsters. AB - LH concentrations were measured in serum collected at 10-min intervals from chronically ovariectomized female Syrian hamsters that had been maintained for 9 wk in stimulatory (long) or inhibitory (short) photoperiods. Short days reduced the number of detectable LH pulses during both the morning and the afternoon. Most short-day hamsters experienced a gradual afternoon rise in serum LH concentrations; this rise was not composed of multiple pulses. In separate groups of similarly treated hamsters, pituitary LH-beta mRNA abundance was significantly reduced by short-day exposure at both times of day even though serum LH concentrations rose in the afternoon. Estradiol treatment induced an afternoon surge of serum LH in both photoperiods, and eliminated the effect of photoperiod on LH-beta mRNA abundance in the afternoon. Serum prolactin (PRL) concentrations were not consistently influenced by day length in castrated hamsters with or without estrogen treatment, but PRL mRNA abundance was significantly suppressed by short-day exposure in all groups. The results indicate that day length exerts profound steroid-independent effects upon hypophyseal gene expression, and that the regulation of LH-beta mRNA abundance may be due to photoperiodic control of the neural GnRH pulse generator. PMID- 1637951 TI - Changes in peripheral levels of bioactive and immunoreactive inhibin, estradiol 17 beta, progesterone, luteinizing hormone, and follicle-stimulating hormone associated with follicular development in cows induced to superovulate with equine chorionic gonadotropin. AB - Changes in concentrations of bioactive and immunoreactive (ir-) inhibin, estradiol-17 beta, progesterone, LH, and FSH in peripheral blood were determined in cows induced to superovulate with eCG. The pattern of follicular growth was also characterized by daily ultrasonographic examination. Hormonal profiles and follicular development during the intact estrous cycle of the same animals before eCG treatment served as controls. Equine CG increased the number of follicles of various sizes (small, greater than or equal to 4 less than 7, medium, greater than or equal to 7 less than 10; large, greater than or equal to 10 mm in diameter) by 4 days after administration. The second growth of large follicles occurred within 1 day after superovulation. Inhibin bioactivity in jugular vein blood was detectable 48 h after eCG injection (44 h before LH peak), whereas it was not detected before administration of eCG or during control cycles. Circulating levels of bioactive inhibin further increased during the two waves of growth of large follicles. The highest activity of inhibin was noted at the time of the preovulatory LH peak (0 h). Thereafter, bioactivity of inhibin in peripheral plasma dropped from 0 to 24 h after the LH peak, and the activity increased again at 72 h compared to the value at -44 h. Plasma levels of ir inhibin showed a pattern similar to changes in bioactive inhibin in the eCG treated cows. Plasma concentrations of estradiol-17 beta also increased concomitantly with two waves of growth of large follicles. There was no correlation between plasma levels of progesterone and inhibin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1637952 TI - Effect of estriol on the structure and organization of collagen in the lamina propria of the immature rat uterus. AB - Estradiol produces both hypertrophic and hyperplastic changes in the uterus, and these changes are associated with alterations in the structure of collagen in the lamina propria. Estriol induces only hypertrophic responses in the immature rat uterus; its effects on collagen structure were characterized in this study. Light micrographs of Masson's trichrome-stained sections revealed that the intensity of the collagen stain in the lamina propria of the rat uterus was profoundly reduced, relative to that in controls, 4 h after estriol (40 micrograms/kg) administration. These changes were not evident 24 h after estriol administration. In control uteri, transmission electron micrographs revealed that the collagen fibers surrounding stromal cells formed dense collections of bundles that were seen throughout the extracellular matrix, whereas in tissues exposed to estriol 4 h earlier, large regions of the extracellular spaces were devoid of collagen bundles. The 4-h changes in collagen were eliminated when animals were pretreated with actinomycin D (8 mg/kg) or cycloheximide (4 mg/kg). Dense collections of collagen bundles were present in tissues 24 h after estriol treatment, and their appearance was not altered by actinomycin D or cycloheximide treatment. Alterations in collagen 4 h after hormone administration appeared to be estrogen specific since dexamethasone (600 micrograms/kg) and dihydrotestosterone (400 micrograms/kg) had no effect. These data provide evidence that the changes in collagen structure in the uterus are associated with events that function during the hypertrophic growth responses induced by estrogens. PMID- 1637953 TI - The effect of testosterone withdrawal and subsequent germ cell depletion on transferrin and sulfated glycoprotein-2 messenger ribonucleic acid levels in the adult rat testis. AB - We have examined the effects of decreasing intratesticular testosterone concentration and of decreasing germ cell number on levels of transferrin mRNA and sulfated glycoprotein (SGP)-2 mRNA in the adult rat testis. Intact rats received implants of testosterone- and estradiol-filled capsules to suppress LH secretion from the pituitary, thereby suppressing Leydig cell testosterone production. The levels of intratesticular testosterone declined 70% to 20 ng/ml within 3 days, were reduced further to approximately 15 ng/ml by 14 days, and subsequently reached a minimum of about 10 ng/ml. In contrast, the number of elongated spermatids per testis remained unchanged through 14 days, then declined to fewer than 20% of normal between 14 and 28 days, and reached zero by 56 days postimplantation. Likewise, both pachytene spermatocytes and round spermatids declined only after 14 days postimplantation. Northern blots of testicular RNA showed that Sertoli cell transferrin mRNA per testis decreased markedly between 14 and 28 days postimplantation. However, SGP-2 mRNA per testis was unchanged over the time course of the experiment. The decrease in transferrin mRNA, concomitant with germ cell loss, suggests that this mRNA is regulated by the number of germ cells in the testis and not directly by testosterone. In contrast, the constant level of SGP-2 mRNA in the face of reduced intratesticular testosterone and the subsequent loss of germ cells suggests that this mRNA is constitutively maintained in the adult rat testis. PMID- 1637954 TI - Differences in the characteristics and distribution of rat luteal receptors for native and deglycosylated human choriogonadotropin. AB - Previous work has suggested that rat luteal cells have two populations of LH/hCG receptors that are located in different parts of the cell membrane. The possibility that these two receptor pools may have functional differences has been investigated through examination of the binding and action of native and deglycosylated hCG to different membrane fractions. Ovaries from eCG/hCG-primed immature female rats were separated into 1,000 x g (heavy) and 20,000 x g (light) particulate fractions. Increasing concentrations of NaCl had a biphasic effect on the binding of native and deglycosylated hCG to both membrane fractions, causing an increase in binding at low concentrations and a decrease in binding at higher concentrations. The binding of deglycosylated hCG to both membrane preparations and the binding of native hCG to light-membrane preparations was maximal at approximately the same NaCl concentration (50-65 mM). This was higher than the concentration of NaCl necessary for maximal binding of native hCG to the heavy membrane preparation. In addition, maximal native hCG binding to this preparation occurred over a broader NaCl concentration range (15-65 mM). Equilibrium binding experiments showed differences in hCG binding to both fractions. In light membranes there were significantly more receptor sites for deglycosylated hCG (11.2 +/- 4.8 fmol/mg ovary) than for native hCG (4.8 +/- 0.7 fmol/mg ovary), with no significant different in affinity. In contrast, in heavy membranes the affinity for deglycosylated hCG (6.30 +/- 0.19.10(9) M-1), was significantly higher than that for native hCG (2.60 +/- 0.13.10(9) M-1), with no significant differences in receptor number.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1637955 TI - [The behavior of BAEE-lytic proteinases in the sulcus fluid in inflammatory periodontopathies]. AB - The esterolytic activity of proteinases was measured in the gingival crevicular fluid from healthy and inflamed periodonts using BAEE as substrate. The BAEE activity was significantly increased in crevices with inflamed periodonts. PMID- 1637956 TI - [The treatment of neuralgiform facial pains with the combined therapy of transcutaneous electric nerve stimulation (TENS) and the iontophoresis of nonsteroidal antiphlogistics]. AB - In a prospective study, 46 patients suffering from facial pain were treated by transcutaneous electrical nerve stimulation (TENS). In case of insufficient pain relief the combined use of TENS and iontophoresis of non-steroidal antiphlogistics was employed. Benzydamine was applied to the anode and diclofenac to the cathode instead of the contact gel, reducing average pain intensity to a marked 18%, compared to 81% to 63% by TENS only. Furthermore, the consumption of analgetics declined considerably with combined therapy. Severe side effects could not be registered. Therefore, this new combined therapy must be considered to be an alternative treatment before using systemic medication. PMID- 1637957 TI - [The pre- and intraoperative localization of superficially situated metallic objects in the head and neck area using a metal detector]. AB - For prevention of infections and with regard to forensic implications foreign bodies lost in the soft tissues should be taken out. A good alternative for the localization of metallic objects superficially situated in the soft tissues of the oral facial region, other than the use of radiographic means and stereotactic localization, is the use of a metal detector. This method can be used without complication before or during each operation demonstrated by two clinical cases. Its use avoids a large-scale tissue removal and exposure in the search of foreign bodies in superficial soft tissues. It is a non invasive simple method for localization of metallic foreign bodies. PMID- 1637958 TI - [Septic granulomatosis (chronic granulomatous disease = CGD) in the jaw area. A case report]. AB - A rare case of chronic granulomatous disease with manifestation in the mandible is presented. A 10-year-old boy showed the clinical picture of osteomyelitis without paresthesia (Vincent syndrome). Diagnosis was done by the nitroblue tetrazolium test (NBT) and by demonstration of a complete cytochrome-b deficiency of the granulocytes. In septic granulomatosis a continuous application of Sulfamethoxazol-Trimetoprim is recommended for prophylaxis of infection. For treatment of infection further antibiotics who pass into the granulocytes like rifampicin and fosfomycin are necessary. Oral surgical procedures request a careful tissue handling and a tight wound closure. PMID- 1637959 TI - [The late results in conservatively treated fractures of the mandibular condylar process]. AB - The results of conservative treatment of 128 patients, who suffered an isolated fracture of the mandibular condylar process at least 5 years ago and their dependence upon localisation and dislocation of the fracture are demonstrated. The advantages and disadvantages of conservative and operative therapy are discussed. PMID- 1637960 TI - [The use of different conscious sedation procedures in ambulatory dental surgery]. AB - Conditions and selections of patients undergoing oral surgery under intravenous conscious sedation are reviewed. The practicability of several medicaments and combinations are discussed. Intravenous conscious sedation in combination with local anesthesia is an alternative during unpleasant surgical and dental procedures, and in several cases, can replace general anesthesia. A sufficient monitoring as well as a good trained staff makes the methods safe and allows to reduce complications. PMID- 1637961 TI - A review of the ability of non-clinical testing strategies currently applied to drugs to detect known human carcinogens. PMID- 1637962 TI - Toxicity of aluminium: a historical review, Part 1. PMID- 1637963 TI - Famous names in toxicology. Mateo Orfila (1787-1853). PMID- 1637964 TI - Adverse effects of the lipid-lowering drugs. PMID- 1637965 TI - On the design of genome mapping experiments using short synthetic oligonucleotides. AB - The DNA of an organism can be digested into smaller fragments, stored individually as clones in phage, for example, to create a clone library, and retrieved later, when needed. The original ordering of fragments is lost in the process of creating the library. Hence, it is important to be able to place clones in order according to their position along chromosome(s), and this process is referred to as "in vitro reconstruction" or "contig mapping" of an organismal genome. Clones in the phage library can be assigned binary call numbers by scoring each clone for hybridization (0 or 1) with a battery of short manufactured DNA sequences called synthetic oligonucleotides or with restriction enzyme digests of each clone. Those clones with similar call numbers are placed close together in the ordered library. We address the design question of how many clones and probes to use to carry out in vitro reconstruction of an organism's chromosomes. This physical mapping problem is placed in the context of coverage problems in geometrical probability. Various statistics are developed to summarize how an ordered library covers a chromosome, the extent of clone overlap, and the similarity between clone call numbers. Several tests for whether clones overlap are given, together with their power properties. A simulation study is used to determine how robust some of the tests for clone overlap are to model violations. Tables are presented for researchers to choose the number of clones and probes on the basis of both power and technical considerations surrounding the hybridization experiments. PMID- 1637966 TI - Performing the exact test of Hardy-Weinberg proportion for multiple alleles. AB - The Hardy-Weinberg law plays an important role in the field of population genetics and often serves as a basis for genetic inference. Because of its importance, much attention has been devoted to tests of Hardy-Weinberg proportions (HWP) over the decades. It has long been recognized that large-sample goodness-of-fit tests can sometimes lead to spurious results when the sample size and/or some genotypic frequencies are small. Although a complete enumeration algorithm for the exact test has been proposed, it is not of practical use for loci with more than a few alleles due to the amount of computation required. We propose two algorithms to estimate the significance level for a test of HWP. The algorithms are easily applicable to loci with multiple alleles. Both are remarkably simple and computationally fast. Relative efficiency and merits of the two algorithms are compared. Guidelines regarding their usage are given. Numerical examples are given to illustrate the practicality of the algorithms. PMID- 1637967 TI - A new procedure for group sequential analysis in clinical trials. AB - Since Pocock (1977, Biometrika 64, 191-199), many methods have been developed for group sequential analysis of clinical trials. However, these methods remain underemployed partly because of inconsistencies of sequential testing [Berry (1987, The Statistician 36, 181-189)]. This paper considers a new approach, which, by requiring that a succession of interim analyses be significant at the alpha level, both preserves the overall significance level alpha and does not present some of the inconsistencies of the previous methods. Results are obtained for a normal or binary response and for survival data. A comparison with the usual group sequential testing is also presented. PMID- 1637968 TI - Sample size determination for case-control studies and the comparison of stratified and unstratified analyses. AB - Woolson, Bean, and Rojas (1986, Biometrics 42, 927-932) present a simple approximation of sample size for Cochran's (1954, Biometrics 10, 417-451) test for detecting association between exposure and disease. It is useful in the design of case-control studies. We derive a sample size formula for Cochran's statistic with continuity correction which guarantees that the actual Type I error rate of the test does not exceed the nominal level. The corrected sample size is necessarily larger than the uncorrected one given by Woolson et al. and the relative difference between the two sample sizes is considerable. Allocation of equal number of cases and controls within each stratum is asymptotically optimal when the costs per case and control are the same. When any effect of stratification is absent, Cochran's stratified test, although valid, is less efficient than the unstratified one except for the important case of a balanced design. PMID- 1637969 TI - When does it pay to break the matches for analysis of a matched-pairs design? AB - Two methods of analysis are compared to estimate the treatment effect of a comparative study where each treated individual is matched with a single control at the design stage. The usual matched-pairs analysis accounts for the pairing directly in its model, whereas regression adjustment ignores the matching but instead models the pairing using a set of covariates. For a normal linear model, the estimated treatment effect from the matched-pairs analysis (paired t-test) is more efficient. For a Bernoulli logistic model, matched-pairs analysis performs better when the sample size is small, but is inferior to logistic regression for large sample sizes. PMID- 1637970 TI - Relative risk trees for censored survival data. AB - A method is developed for obtaining tree-structured relative risk estimates for censored survival data. The first step of a full likelihood estimation procedure is used in a recursive partitioning algorithm that adopts most aspects of the widely used Classification and Regression Tree (CART) algorithm of Breiman et al. (1984, Classification and Regression Trees, Belmont, California: Wadsworth). The performance of the technique is investigated through stimulation and compared to the tree-structured survival methods proposed by Davis and Anderson (1989, Statistics in Medicine 8, 947-961) and Therneau, Grambsch, and Fleming (1990, Biometrika 77, 147-160). PMID- 1637971 TI - Estimation of the size distribution of fibrillar centres in nucleoli--an example of the "Swiss cheese" problem in stereology. AB - The "Swiss cheese" problem in stereology is that variant of the classical corpuscle problem where the size distribution of randomly distributed spherical "holes" in an opaque medium is to be inferred from the size distribution of the circular holes observed in sections. In our electron microscopical studies of the neurons of the rat supraoptic nucleus, we encountered a Swiss cheese problem in connection with the size distribution of the fibrillar centres of the nucleoli. We found no practical examples in the literature, and attempts to obtain a Wicksell-type algorithm met with severe numerical instability problems. The present paper shows that the chi-distributions of Keiding, Jensen, and Ranek (1972, Biometrics 28, 813-829) may be used as the basis for a parametric maximum likelihood solution for the Swiss cheese problem. The concept of a capping angle (nonobservability of spheres cut at too acute an angle), also introduced by Keiding et al., carries over as well. The methods are illustrated on data from the mentioned experiment. PMID- 1637972 TI - On the use of historical control data to estimate dose response trends in quantal bioassay. AB - New tests for trend in proportions, in the presence of historical control data, are proposed. One such test is a simple score statistic based on a binomial likelihood for the "current" study and beta-binomial likelihoods for each historical control series. A closely related trend statistic based on estimating equations is also proposed. Trend statistics that allow overdispersed proportions in the current study are also developed, including a version of Tarone's (1982, Biometrics 38, 215-220) test that acknowledges sampling variation in the beta distribution parameters, and a trend statistic based on estimating equations. Each such trend test is evaluated with respect to size and power under both binomial and beta-binomial sampling conditions for the current study, and illustrations are provided. PMID- 1637973 TI - Estimating exposure effects by modelling the expectation of exposure conditional on confounders. AB - In order to estimate the causal effects of one or more exposures or treatments on an outcome of interest, one has to account for the effect of "confounding factors" which both covary with the exposures or treatments and are independent predictors of the outcome. In this paper we present regression methods which, in contrast to standard methods, adjust for the confounding effect of multiple continuous or discrete covariates by modelling the conditional expectation of the exposures or treatments given the confounders. In the special case of a univariate dichotomous exposure or treatment, this conditional expectation is identical to what Rosenbaum and Rubin have called the propensity score. They have also proposed methods to estimate causal effects by modelling the propensity score. Our methods generalize those of Rosenbaum and Rubin in several ways. First, our approach straightforwardly allows for multivariate exposures or treatments, each of which may be continuous, ordinal, or discrete. Second, even in the case of a single dichotomous exposure, our approach does not require subclassification or matching on the propensity score so that the potential for "residual confounding," i.e., bias, due to incomplete matching is avoided. Third, our approach allows a rather general formalization of the idea that it is better to use the "estimated propensity score" than the true propensity score even when the true score is known. The additional power of our approach derives from the fact that we assume the causal effects of the exposures or treatments can be described by the parametric component of a semiparametric regression model. To illustrate our methods, we reanalyze the effect of current cigarette smoking on the level of forced expiratory volume in one second in a cohort of 2,713 adult white males. We compare the results with those obtained using standard methods. PMID- 1637974 TI - A coupling procedure for the discrimination of mixed data. AB - A procedure is described for coupling different discriminators to a new (common) decision rule using the corresponding allocation vectors only. This enables one to cope jointly with data of different structure and/or scales of measurement but without strong restrictions on the number of (especially categorical) features. The method is combined with a consequent cross-validation process securing the results reached. Examples from medical diagnostics demonstrate the usefulness of the proposed procedure, especially in comparison with the known linear discriminant analysis as judged from the error rates obtained. PMID- 1637975 TI - Assessing influence in regression analysis with censored data. AB - In this paper we show how to evaluate the effect that perturbations to the model, data, or case weights have on maximum likelihood estimates from censored survival data. The ideas and methods also apply to other nonlinear estimation problems. We review the ideas behind using log-likelihood displacement and local influence methods. We describe new interpretations for some local influence statistics and show how these statistics extend and complement traditional case deletion influence statistics for linear least squares. These statistics identify individual and combinations of cases that have important influence on estimates of parameters and functions of these parameters. We illustrate the methods by reanalyzing the Stanford Heart Transplant data with a parametric regression model. PMID- 1637976 TI - An empirical assessment of saddlepoint approximations for testing a logistic regression parameter. AB - Saddlepoint methods provide quick and easy approximations to significance levels for conditional tests of logistic regression parameters. We evaluate the accuracies of saddlepoint approximations for three well-known conditional tests: Bartlett's test for no three-factor interaction in a 2 x 2 x 2 table, the test for trend in a series of probabilities, and the exact test of no association in stratified 2 x 2 tables with a common odds ratio. General recommendations are suggested regarding the use of saddlepoint approximations for exact conditional significance levels. PMID- 1637977 TI - Maximum-penalized-likelihood estimation for independent and Markov-dependent mixture models. AB - This paper concerns the use and implementation of maximum-penalized-likelihood procedures for choosing the number of mixing components and estimating the parameters in independent and Markov-dependent mixture models. Computation of the estimates is achieved via algorithms for the automatic generation of starting values for the EM algorithm. Computation of the information matrix is also discussed. Poisson mixture models are applied to a sequence of counts of movements by a fetal lamb in utero obtained by ultrasound. The resulting estimates are seen to provide plausible mechanisms for the physiological process. PMID- 1637978 TI - An inferential procedure for the Poisson intervention parameter. AB - To describe a health chance mechanism whose incidence rate is altered in the middle of a data collection period due to preventive treatments taken by health service agencies, a model called Intervened Poisson Distribution (cf. Shanmugam, 1985, Biometrics 41, 1025-1029) was introduced. In this article, we derive a statistic to test the hypothesis concerning the effectiveness of such preventive treatments, and compare its power with another suggested test (cf. Streit, 1987, Biometrics 43, 999-1000). PMID- 1637979 TI - Interval estimation for mark-recapture studies of closed populations. AB - Textbooks continue to recommend the use of an asymptotic normal distribution to provide an interval estimate for the unknown size, N, of a closed population studied by a mark-recapture experiment or multiple-record system. A likelihood interval approach is proposed and its implementation demonstrated for a range of models for such studies, including all main effect and interaction models for incomplete contingency tables. PMID- 1637980 TI - A simple method for the analysis of clustered binary data. AB - A simple method for comparing independent groups of clustered binary data with group-specific covariates is proposed. It is based on the concepts of design effect and effective sample size widely used in sample surveys, and assumes no specific models for the intracluster correlations. It can be implemented using any standard computer program for the analysis of independent binary data after a small amount of preprocessing. The method is applied to a variety of problems involving clustered binary data: testing homogeneity of proportions, estimating dose-response models and testing for trend in proportions, and performing the Mantel-Haenszel chi-squared test for independence in a series of 2 x 2 tables and estimating the common odds ratio and its variance. Illustrative applications of the method are also presented. PMID- 1637981 TI - On prevalence, incidence, and duration in general stable populations. AB - The relationship between prevalence, incidence, and duration of disease is studied in exponentially growing/declining stable populations. Prevalence odds is shown to be a weighted average of age-specific products between incidence and discounted disease duration. If and only if the covariance between incidence and duration is zero, does prevalence odds equal the product of average incidence and average duration. The product of averages is shown typically to overestimate prevalence in epidemiologic applications. Ignoring population growth also tends to lead to overestimation of prevalence. PMID- 1637982 TI - Use of baseline data for estimation of treatment effects in the presence of regression to the mean. AB - We consider a regression to the mean problem with a very large sample for the first measurement and relatively small subsample for the second measurement, selected on the basis of the initial measurement. This is a situation that often occurs in screening trials. We propose to estimate the unselected population mean and variance from the first measurement in the larger sample. Using these estimates, the correlation between the two measurements, as well as an effect of treatment, can be estimated in simple and explicit form. Under the condition that the size of the subsample is of a smaller order, the new estimators for all the four parameters are as asymptotically efficient as the usual maximum likelihood estimators. Tests based on this new approach are also discussed. An illustration from a cholesterol screening study is included. PMID- 1637983 TI - The effect of diagnostic misclassification on non-cancer and cancer mortality dose response in A-bomb survivors. AB - We used the EM algorithm in the context of a joint Poisson regression analysis of cancer and non-cancer mortality in the Radiation Effects Research Foundation (RERF) Life Span Study (LSS) to assess whether the observed increased risk of non cancer death due to radiation exposure (Shimizu et al., RERF Technical Report 02 91, 1991) can be attributed solely to misclassification of cancer as non-cancer on death certificates. We show that greater levels of dose-independent misclassification than are indicated by a series of autopsies conducted on a subset of LSS members would be required to explain the non-cancer dose response, but that a relatively small amount of dose-dependence in the misclassification of cancer would explain the result. The adjustment for misclassification also results in higher risk estimates for cancer mortality. We review applications of similar statistical methods in other contexts and discuss extensions of the methods to more than two causes of death. PMID- 1637984 TI - Estimating compliance to study medication from serum drug levels: application to an AIDS clinical trial of zidovudine. AB - This paper examines the use of serum drug levels to assess compliance to study medication in a clinical trial. We discuss problems of false-positivity, false negativity, and bias that arise because of experimental errors in the drug assays, pharmacokinetic variations of the drug, and differential dosing levels. Basic concepts in probability are applied to derive a simple model that quantifies these problems. This model is used to obtain an estimate of compliance rate that corrects for these problems. However, derivation of this estimate requires additional information about false-positive and false-negative rates of the assay as well as some knowledge of the pharmacokinetic properties of the drug. We illustrate the evaluation of such a compliance estimate in the setting of an AIDS clinical trial of zidovudine (ZDV), in which some accessory data are available on the properties of ZDV serum assays and on the pharmacokinetic behavior of ZDV. We also describe a method that uses the accessory data to provide the additional information needed for computing the compliance estimate. PMID- 1637985 TI - Generalized linear models with random effects; salamander mating revisited. AB - In recent years much effort has been devoted to extending regression methodology to non-Gaussian data, where responses are not independent. These methods for dependent responses are suitable for data from longitudinal studies or nested designs. However, use of these methods for crossed designs seems to have serious limitations due to the intensive computations involved because of the intractable nature of the joint distribution. In this paper, we cast the problem in a Bayesian framework and use a Monte Carlo method, the Gibbs sampler, to avoid current computational limitations. The flexibility of this approach is illustrated by analyzing the interesting salamander mating data reported by McCullagh and Nelder (1989, Generalized Linear Models, 2nd edition, London: Chapman and Hall). PMID- 1637986 TI - Efficacy of repeated measures in regression models with measurement error. AB - Ignoring measurement error may cause bias in the estimation of regression parameters. When the true covariates are unobservable, multiple imprecise measurements can be used in the analysis to correct for the associated bias. We suggest a simple estimating procedure that gives consistent estimates of regression parameters by using the repeated measurements with error. The relative Pitman efficiency of our estimator based on models with and without measurement error has been found to be a simple function of the number of replicates and the ratio of intra- to inter-variance of the true covariate. The procedure thus provides a guide for deciding the number of repeated measurements in the design stage. An example from a survey study is presented. PMID- 1637987 TI - Helix-forming tendencies of amino acids depend on the restrictions of side-chain rotamer conformations: crystal structure of the tripeptide GAI in two crystalline forms. AB - In our attempts to design crystalline alpha-helical peptides, we synthesized and crystallized GAI (C11H21N3O4) in two crystal forms, GAI1 and GAI2. Form 1 (GAI1) Gly-L-Ala-L-Ile (C11H21N3O4.3H2O) crystals are monoclinic, space group P2(1) with a = 8.171(2), b = 6.072(4), c = 16.443(4) A, beta = 101.24(2) degrees, V = 800 A3, Dc = 1.300 g cm-3 and Z = 2, R = 0.081 for 482 reflections. Form 2 (GAI2) Gly L-Ala-L-Ile (C11H21N3O4.1/2H2O) is triclinic, space group P1 with a = 5.830(1), b = 8.832(2), c = 15.008(2) A, alpha = 102.88(1), beta = 101.16(2), gamma = 70.72(2) degrees, V = 705 A3, Z = 2, Dc = 1.264 g cm-3, R = 0.04 for 2582 reflections. GAI1 is isomorphous with GAV and forms a helix, whereas GAI2 does not. In GAI1, the tripeptide molecule is held in a near helical conformation by a water molecule that bridges the NH3+ and COO- groups, and acts as the fourth residue needed to complete the turn by forming two hydrogen bonds. Two other water molecules form intermolecular hydrogen bonds in stabilizing the helical structure so that the end result is a column of molecules that looks like an incipient alpha-helix. GAI2 imitates a cyclic peptide and traps a water molecule. The conformation angles chi 11 and chi 12 for the side chain are (-63.7 degrees, 171.1 degrees) for the helical GAI1, and (-65.1 degrees, 58.6 degrees) and (-65.0 degrees, 58.9 degrees) for the two independent nonhelical molecules in GAI2; in GAI1, both the C gamma atoms point away from the helix, whereas in GAI2 the C gamma atom with the g+ conformation points inward to the helix and causes sterical interaction with atoms in the adjacent peptide plane. From these results, it is clear that the helix-forming tendencies of amino acids correlate with the restrictions of side-chain rotamer conformations. Both the peptide units in GAI1 are trans and show significant deviation from planarity [omega 1 = 168(1) degrees; omega 2 = -171(1) degrees] whereas both the peptide units in both the molecules A and B in GAI2 do not show significant deviation from planarity [omega 1 = 179.3(3) degrees; omega 2 = -179.3(3) degrees for molecule A and omega 1 = 179.5(3) degrees; omega 2 = -179.4(3) degrees for molecule B], indicating that the peptide planes in these incipient alpha-helical peptides are considerably bent. PMID- 1637988 TI - Molecular conformation of ascidiacyclamide, a cytotoxic cyclic peptide from Ascidian: X-ray analyses of its free form and solvate crystals. AB - In order to investigate the conformational variation of ascidiacyclamide, a cytotoxic cyclic peptide from marine tunicate Ascidian, single crystals were prepared from ethanol and aqueous ethanol solutions as its free form (crystal I) and H2O/0.5 C2H5OH solvate (crystal II), respectively, and were determined by the x-ray diffraction method. Crystal I showed a pseudo C2-symmetric saddle-shaped rectangular conformation. Similar conformations were also observed in crystal II, where there were two crystallographically independent C2-symmetric molecules (named Mol-A and -B) per asymmetric unit. Mol-A and -B included H2O and H2O/C2H5OH solvents within their ring structures, respectively. These water and ethanol molecules were located on the crystallographic dyad axes, and were stabilized by the van der Waals contacts (including hydrogen bonds) with the polar-ring N atoms and nonpolar D-Val side-chain atoms. The conformational characteristics of ascidiacyclamide and its fluctuation/variation were discussed based on the present and previously reported x-ray results. PMID- 1637989 TI - The electrostatic contribution to DNA base-stacking interactions. AB - Base-stacking and phosphate-phosphate interactions in B-DNA are studied using the finite difference Poisson-Boltzmann equation. Interaction energies and dielectric constants are calculated and compared to the predictions of simple dielectric models. No extant simple dielectric model adequately describes phosphate phosphate interactions. Electrostatic effects contribute negligibly to the sequence and conformational dependence of base-stacking interactions. Electrostatic base-stacking interactions can be adequately modeled using the Hingerty screening function. The repulsive and dispersive Lennard-Jones interactions dominate the dependence of the stacking interactions on roll, tilt, twist, and propellor. The Lennard-Jones stacking energy in ideal B-DNA is found to be essentially independent of sequence. PMID- 1637990 TI - Molecular dynamics study of the conformational behavior of a representative elastin building block: Boc-Gly-Val-Gly-Gly-Leu-OMe. AB - The conformational behavior of the synthetic peptide, Boc-Gly-Val-Gly-Gly-Leu OMe, containing the X-Gly-Gly and Gly-Gly-X (X = Val or Leu) repeating sequences and constituting a fragment of elastin was investigated by molecular mechanics and molecular dynamics (MD) simulation. The results suggest that, irrespective of the approximations used, the molecule shows a manifold of low energy conformations characterized by gamma-turns and type II beta-turns. Furthermore, MD simulations point out a conformational floppiness due to very low barriers between different conformations. Experimental CD measurements in a virtually apolar medium (dioxane--epsilon = 2.209), which better mimics the vacuum conditions of the simulation, support the theoretical results. The general emerging picture, indicating the molecule as characterized by a combination of flexibility with conformational preferences, is in agreement with previous experimental findings and enriches of new aspects the description of the microscopic behavior of this molecule suggesting more detailed interpretation of previous data. PMID- 1637991 TI - Beta-alanine containing peptides: a novel molecular tool for the design of gamma turns. AB - In the present paper we describe the synthesis, purification, single crystal x ray analysis, and solution conformational characterization of the cyclic tetrapeptide cyclo-(L-Pro-beta-Ala-L-Pro-beta-Ala). This peptide was synthesized by classical solution methods and the cyclization of the free tetrapeptide was accomplished in good yields in diluted methylene chloride solution using N,N dicyclohexyl-carbodiimide (DCCI). The compound crystallizes in the orthorombic space group P2(1)2(1)2(1) from ethyl acetate. All peptide bonds are trans. The molecular conformation is stabilized by two intramolecular hydrogen bonds between the CO and NH groups of the two beta-alanine residues. These hydrogen bonds take place in a C7 structure in which both proline residues occupy the 2 position of an inverse gamma-turn. The two beta-alanine residues have a typical folded conformation (around the C alpha-C beta bond) observed in other cyclic peptides containing this residue. A detailed 1H-nmr analysis in CD3CN solution has been carried out. The molecule assumes a twofold symmetry in solution with a molecular conformation consistent with that observed in the solid state. PMID- 1637992 TI - Helix formation in poly (N epsilon,N epsilon,N epsilon-trimethyl-L-lysine) and poly (L-lysine): dependence on concentration and molecular weight. AB - Helix formation in (Lys)n.HClO4 and poly(N epsilon,N epsilon,N epsilon-trimethyl L-lysine).HClO4 +AD(LysMe3)n.HClO4+BD is dependent on peptide concentration and on molecular weight. For (LysMe3)n.HClO4 of degree of polymerization (DP) 2510 the midpoint of the coil-to-helix transition is 2 mM and for DP of 190 it is 5 mM. For (Lys)n.HClO4 the peptide concentration for half-helix is 30-60 times as high, and is only weakly dependent, if at all, on molecular weight. Helix formation is an intermolecular process. The use of methylated (Lys)n as the perchlorate permits study of the intermolecular coil-helix transition at low concentration, instead of the high concentration (ca. 1-2 M) required for (Lys)n.HBr. At constant peptide concentration helix content increases with added NaClO4. The higher the peptide concentration, the less NaClO4 is needed to induce helix. PMID- 1637993 TI - Bound water in the collagen-like triple-helical structure. AB - The ir amide bands of the triple-helical polytripeptides and collagens upon hydration of films are investigated. On the basis of our assignment of the amide I components, the formation of hydrogen bonds between the peptide backbone and structural water is studied. The C1O1--HOH hydrogen bonds are found more ordered than the C3O3--HOH hydrogen bonds. The specific incorporation of water in the triple helix is followed by multistep conformational changes and by increasing of the interpeptide hydrogen-bond strength. The formation of the polypeptide hydrate structure depending on the amino acid composition and the chain length is examined. PMID- 1637994 TI - [Is conventional tomography still necessary?]. PMID- 1637995 TI - Acro-osteolysis of the phalanges and phaeochromocytoma. PMID- 1637996 TI - [Vascular diagnosis with color-coded duplex sonography]. PMID- 1637997 TI - [The magnetic resonance tomographic signs of Wegener's granulomatosis in the head area]. AB - MRI of the head was performed in 25 patients suffering from Wegener's granuloma. 23 patients showed evidence of mucosal thickening in the paranasal sinuses, the middle and inner ears and in the mastoid cells; these were characterised by low signal intensity of T1-weighted and high signal intensity of T2-weighted images. In 10 patients there were granulomas in the paranasal sinuses and in the orbits which showed low signal intensity of both T1-weighted and T2-weighted images. In 4 patients, additional images were obtained after the intravenous injection of Gd DTPA. In 2 patients this resulted in non-homogeneous contrast accumulation in the granuloma. In 7 patients there were signal changes in the brain which were typical of infarcts. The complete extent of bone destruction in the facial skeleton was visible only by CT. PMID- 1637998 TI - [MR angiography. Its use in pulmonary and mediastinal space-occupying lesions]. AB - MR angiography (MRA) proved to be promising combined to MR imaging (MRI) in the assessment of intrathoracic masses. Sequential FLASH 2D angiograms were acquired in breath-hold technique using the following parameters: TR = 30 ms, TE = 10 ms, FA = 30 degrees. Section thickness was 5 mm with 1 mm overlap between sequential sections. Individual conditions of the examination were achieved by an automatized control procedure. Targeted MIP postprocessing resulted in 3D reconstructions illustrating vascular anatomy and avoiding superimposition. Presentation should be done by cine-mode for better spatial impression. This method was evaluated in a prospective study of 21 patients with malignant pulmonary and mediastinal masses in addition to spin-echo imaging. The diagnostic contribution concerning the relationship between the mass and the vasculature like displacement, stenosis, and poststenotic perfusion defect were assessed. PMID- 1637999 TI - [High-resolution computed tomography (HR-CT) of the lung before transplantation. The value of methods for evaluating the recipient]. AB - We examined the lungs of 49 patients with end-stage lung disease non-responding to conventional therapy when referred to lung transplantation by means of high resolution computed tomography (HR-CT). In 24 of these patients lung transplantation has been performed meanwhile. All scans were evaluated separately for both lungs with special regard to presence and extend to the following findings, in order to select the adequate type of transplantation procedure: pleural thickening, bullae and bronchiectasis. In patients with end-stage emphysema the severity of parenchymal damage was recorded additionally. In 20 patients (40.8%) HR-CT results had a major impact on the selection of the surgical procedure. In 16 cases single lung transplantation was recommended because parenchymal changes were either localised unilaterally or a significant difference regarding the severity of emphysematous changes from one side to the other. In 4 cases double lung transplantation was the adequate procedure due to bilateral bronchiectasis or bullae. Based upon these results HR-CT seems indispensable in patients prior to lung transplantation. PMID- 1638000 TI - [Percutaneous CT-controlled cutting-needle biopsy of diffuse interstitial and alveolar lung diseases--the technic and results]. AB - Twenty-three patients underwent CT-guided large-bore biopsy of diffuse lung disease of clinically and radiologically indeterminate etiology. The procedure was preceded by negative transbronchial biopsy in 20 cases. CT-guided biopsies were performed with a 14-gauge Trucut-needle. Obtaining at least 3 specimens of different parts of the diseased area, a correct histologic diagnosis was achieved in all cases. The size of the histologic specimens (mean: 5-6 mm) exceeded that of the specimens obtained by transbronchial biopsy as reported in the literature. Two major complications occurred and included a rapidly developing tension pneumothorax treated by a small-bore catheter and one self-limited hemoptysis. Major advantages of percutaneous CT-guided biopsy are the nonsuperimposed and very sensitive imaging of lung alterations in diffuse lung diseases that allows evidence of adjacent less and more involved areas accessible by one biopsy approach. CT-guided large-bore biopsy with a cutting needle seems to be a very promising, accurate method in the pathomorphologic work-up of diffuse lung diseases rendering open biopsy unnecessary in many cases. PMID- 1638001 TI - [The clinical relevance of anti-CEA immunoscintigraphy with the 99mTc-labelled monoclonal antibody BW 431/26. A critical assessment after 119 studies]. AB - The results of 119 radioimmunoscintigraphies (RIS) in 113 patients with the 99mTc labeled monoclonal anti-CEA-antibody BW 431/26 (Behring) have been analysed. The aim of our study was the estimation of the method's sensitivity and specificity under different aspects to find out for which indications and questions the 99mTc RIS is useful. Colorectal primary tumours in 19 patients were scintigraphically detected with a sensitivity of 83% and a specificity of 100%; 3 out of 7 other tumour sites were localised correctly. 55 patients were examined during the follow-up of colorectal cancer. There were 17 out of 22 true positive findings of local recurrences (sensitivity 77%, specificity 88%). Liver metastases were imaged as hot lesions with only 41% sensitivity and 86% specificity. The detection of extrahepatic tumour sites is difficult because of the persistently high blood-pool activity of the monoclonal antibody and, in the pelvic area, the unspecific bowel activity. Skeletal metastases were recognised in 7 out of 9 cases. In 14 patients with other non-colorectal carcinomas, RIS was successful in single cases. It is not helpful, however, when searching for tumours of unknown origin or for the screening of patients with elevated CEA levels without tumour history. The high technical, methodological and time effort required by RIS is justified in the follow-up of cancer patients when conventional diagnostic procedures are inconclusive or the status of morphological findings remains unclear. The use of RIS as an unspecific screening tool in tumour diagnosis must be rejected because of the not completely explored risks of the examination. Repeated applications of monoclonal antibodies require controls of the patients' HAMA titers before performing RIS. PMID- 1638002 TI - [Radiological findings in pseudohypoparathyroidism]. AB - Clinical and radiodiagnostic changes in pseudohypoparathyroidism are described in three members of one family. Radiodiagnostic changes consist of symmetric calcifications in basal ganglia, perivascular calcifications in soft tissues, and of alterations on the skeleton--Albright's osteodystrophy. Bone changes include a combination of osteoproductive and osteomalacic alterations. All these changes were observed in both brothers, their mother had only calcifications localised in upper and lower extremities. PMID- 1638003 TI - [MR tomography versus CT arthrography in glenohumeral instabilities]. AB - In a prospective study the diagnostic value of MRI compared to CT arthrography (CT-A) was evaluated in 26 patients with 27 instable shoulder joints. Surgical and/or arthroscopic correlation was available in all cases. Both methods showed a high accuracy (96% CT-A, 94% MRI) in the evaluation of the glenoid labrum. CT-A was significantly superior to MRI in the detection of capsular lesions (sensitivity 96% vs. 44%, accuracy 96% vs. 72%, negative predictive value 96% vs. 67%). CT-A and MRI results regarding humeral head fractures were similar; fractures of the glenoid rim were better detected by CT-A, the difference, however, was statistically not significant. Overall, CT-A proved to be superior to MRI, as lesions of the joint capsule were shown with greater certainty. PMID- 1638004 TI - [Apophyseal elements of the sacroiliac joint in the computed tomographic image]. AB - Between the ages of 12 and 18 years apophyseal elements appear within the SI joints which fuse subsequently with the sacrum. These apophyses could be demonstrated during two autopsies on juveniles and were seen in 7 CT examinations of patients between the ages of 15 and 19. On CT they appeared as narrow, round or band-like opacities situated on the ventral aspect of the joint. The differentiation of these normal findings from pathological changes within the SI joints is discussed. PMID- 1638005 TI - [Epiphyseal dysplasia of the hip joint, its diagnosis and differential diagnosis with MRT]. AB - Sixteen hip joints of eight patients with multiple epiphyseal dysplasia were examined by clinical investigation, plain films and by magnetic resonance imaging (MRI), using T1- and T2-weighted images and gradient echoes. MRI is useful in demonstrating the congruity of the joint, in the changes of the epiphyseal signal intensities and the epiphyseal line. Individual changes of the signal intensity patterns on T1- and T2-weighted scans are described. Although MRI exhibits a variety of patterns in different patients, a clearcut differentiation from Legg Calve-Perthes' disease is possible. PMID- 1638006 TI - [Magnetic resonance tomographic screening studies of the bone marrow with gradient-echo sequences. II. Gadolinium-DTPA-supported studies of plasmocytoma patients]. AB - MR imaging was performed in 19 patients with proven multiple myeloma. Both plain and Gd-DTPA enhanced in-phase and opposed-phase gradient-echo techniques were used (0.1 mmol Magnevist/kg body weight). Plain, opposed-phase imaging demonstrated more lesions than plain in-phase imaging (35 vs. 16); enhanced opposed-phase imaging demonstrated more lesions than plain opposed-phase and enhanced in-phase imaging (47 vs. 35 and 17 lesions). These results suggest that enhanced opposed-phase images which have a high contrast between normal and infiltrated bone marrow are especially suited for MR screening in multiple myeloma. PMID- 1638007 TI - [The evaluation of 2D- and 3D-"time of flight" magnetic resonance angiography (MRA) in the diagnosis of renal artery stenoses]. AB - This study was carried out to evaluate time-of-flight RA in renal artery stenosis (RAS) in selected hypertensive patients (n = 41). In i.a. DSA studies, 10 unilateral, 8 bilateral RAS, and 4 unilateral RA occlusions were proven. MRA was done in coronal and axial 2D technique (FLASH), and in 3D technique (FISP) using GE-pulse sequences. DSA results were correlated with both 2D-individual slices, 2D- and 3D-MIP angiograms. Highest sensitivity and specificity was found for the axial 2D individual slice analysis (88%, 85% resp.), followed by the 3D-MIP MRA (78%, 80% resp.), and axial 2D-MIP MRA (73%, 79% resp.). MRA of renal arteries used in this study shows to be not adequate to DSA results due to many drawbacks. All MRA techniques, in particular the 3D-technique, tend to overestimate RAS occasionally pretending occlusions. PMID- 1638008 TI - [Ureteropelvic stenosis in infancy. The value of diuresis sonography compared with diuresis excretory urography]. AB - Examinations under conditions of diuresis produced by drugs can be useful to differentiate pyelo-ureteric obstruction from a dilated collecting system with normal flow. 22 infants with 42 kidneys showing moderate dilatation of one of both renal collecting systems were examined by sonography and excretory urography under conditions of diuresis and the results were compared. Depending on the radiological appearances and contrast clearance rates, four diagnostic groups could be identified; these also differed significantly on the sonographic examinations. In general, there was good agreement between the two methods. Carefully performed, diuresis sonography will clearly distinguish between urodynamically significant obstruction from a wide but non-obstructive collecting system. The number of radiographic examinations can therefore be reduced in these patients. PMID- 1638009 TI - [Cystic space-occupying lesions of the seminal vesicles. Their demonstration with MRT]. AB - Between October 1990 and March 1991, 8 patients with cystic lesions in the region of the posterior bladder wall, the seminal vesicles and the prostate were examined by MRI. In all cases there was accurate characterisation of the lesion and of its anatomy. In 3 patients with abnormalities in the retrovesical space there was very good agreement with the operative findings. 4 patients were treated conservatively. In these patients there was good agreement with the findings on cystoscopy, CT and sonography. PMID- 1638010 TI - [The visualization of bony and vascular structures in digital subtraction images depending on the contribution of the anatomical background]. AB - We examined the loss of contrast leaving a part of the anatomic background in digital subtraction angiography by visual analysis and densitometry. We observed a greater loss of the quality at the representation of the bone below than above an amount of anatomic background of 60%. The loss of quality at the representation of the vessels decreases more above than below an anatomical background of 45%. We think that, depending on the clinical problem, an anatomical background between 15 and 30% should be left. PMID- 1638011 TI - High flow run-off angiography. Timing of film sequence. PMID- 1638012 TI - [Transfemoral catheter blockade of the vena cava inferior for the thrombectomy of a pelvic venous thrombosis]. PMID- 1638013 TI - Cholesterol granuloma of the petrous apex with peritubal extension. PMID- 1638014 TI - [The clinical picture of neurosarcoidosis. The MR tomographic follow-up]. PMID- 1638015 TI - [The CT image of a hemangioleiomyoma of the kidney]. PMID- 1638016 TI - Development of iron-chelating agents for clinical use. PMID- 1638017 TI - GATA-binding transcription factors in hematopoietic cells. PMID- 1638018 TI - Efficacy and possible adverse effects of the oral iron chelator 1,2-dimethyl-3 hydroxypyrid-4-one (L1) in thalassemia major. AB - Eleven patients with beta thalassemia major were entered into the trial of the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1). Their ages ranged from 17 to 26 years (mean +/- SD, 22.3 +/- 2.7). Six were male and five were female. L1 was administered at an initial daily dose of 42.5 to 60 mg/kg as a single dose. After 4 weeks, the dose was increased to 85 to 119 (102 +/- 10.7) mg/kg for 191 to 352 days divided into either two or four doses daily, except for one patient who developed agranulocytosis after 11 weeks and was taken off the trial. Initial serum ferritin values in the remaining 10 patients ranged between 1,000 and 9,580 (5,549 +/- 3,333) micrograms/L and at end of the trial their mean serum ferritin was significantly lower (4,126 +/- 2,278; P less than .05 using the paired t test). Urinary iron excretion at a daily dose of 85 to 119 mg/kg administered as two divided doses ranged between 0.14 and 0.82 (0.44 +/- 0.26) mg/kg/24 h. In three patients, the four doses per day schedule caused substantially more iron excretion than the same total dose divided into two. During the course of the trial, several possible adverse effects have been encountered. One patient (female, aged 20) developed agranulocytosis 11 weeks after starting treatment and 6 weeks after beginning treatment with a daily dose of 105 mg/kg. This patient's neutrophil count recovered spontaneously 7 weeks after the discontinuation of L1. A decrease in serum zinc levels to subnormal levels was observed in four patients with symptoms of dry skin, with an itchy scaly rash in two that was associated with low serum zinc levels that responded to zinc therapy. Urinary zinc levels ranged from 4.7 to 23.4 (13 +/- 5.5) mumol/24 h and were above 9 mumol/24 h (upper limit of normal) in eight patients. Mild nausea occurred in three patients and transient diarrhea in a fourth. Mild musculoskeletal symptoms occurred in three patients but settled without discontinuation of L1 therapy in two and with temporary discontinuation of L1 in the third. A transient increase in serum aspartate transaminase was also noted in five patients, but serum aspartate transaminase levels subsequently decreased in all of them. No cardiovascular, neurologic, renal, or retinal toxicities were demonstrable. These results confirm that L1 is an effective oral iron chelator. Further clinical trials are needed to determine the incidence and severity of adverse effects. PMID- 1638019 TI - Interleukin-3 regulates the activity of the LYN protein-tyrosine kinase in myeloid-committed leukemic cell lines. AB - The lymphokine interleukin-3 (IL-3) promotes the growth and survival of immature hematopoietic cells. Previous studies have shown that IL-3 induces rapid increases in protein-tyrosine kinase (PTK) activity in IL-3--dependent cells. Unlike some other hematopoietic growth factor receptors (eg, c-fms and c-kit), however, the known subunits of the IL-3 receptor (IL-3R) lack intrinsic kinase activity. Recently, it was reported that the IL-2R (whose p75 beta-subunit shares sequence homology with a known murine IL-3R subunit and a common beta-subunit of the human IL-3R and granulocyte-macrophage colony-stimulating factor [GM-CSF] receptors) can physically associate with and regulate the activity of the SRC family PTK, p56-LCK. Because most IL-3--dependent cells contain p53/56-LYN, but not p56-LCK, we explored the effects of IL-3 on the activities of LYN and other SRC-like PTKs in two human leukemic cell lines, AML-193 and TALL-101, which are phenotypically myeloid, and whose in vitro growth is dependent on IL-3. These cells expressed four of the eight known SRC-family proto-oncogenes: lyn, fyn, yes, and hck. When these factor-dependent leukemic cell lines were deprived of lymphokine to achieve cellular quiescence and then restimulated with IL-3, rapid increases (detectable within 1 minute and maximal by 10 minutes) were observed in the activity of the p53/56-LYN kinase, as assessed by in vitro kinase assays. In contrast, no alteration in the activities of other SRC-family PTKs present in these cells was detected after restimulation with IL-3 under the same conditions. This effect of IL-3 reflected an increase in the specific activity of the LYN kinase, because levels of the 53-Kd and 56-Kd LYN proteins were unaltered by IL-3 stimulation, as assessed by immunoblotting. Furthermore, the magnitude of these inducible increases in LYN kinase activity was dependent on the concentration of IL-3, and correlated with IL-3--induced proliferation. The IL-3--induced upregulation of LYN kinase activity may be mediated by the 120-Kd common subunit of the human IL-3 and GM-CSF receptors, because GM-CSF also stimulated marked increases in the activity of the LYN kinase, whereas granulocyte-CSF (G-CSF) did not, despite inducing cellular proliferation. These observations provide the first example of an IL-3--regulable PTK, and strongly suggest that the p53/56-LYN kinase participates in early IL-3--initiated signalling events, at least in some human leukemic cell lines. PMID- 1638020 TI - Comparison of in vitro growth characteristics of blast cell progenitors (CFU-L) in patients with myelodysplastic syndromes and acute myeloid leukemia. AB - Current knowledge is inadequate to explain the different patterns of blast cell accumulation in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We compared the growth patterns of blast cell progenitors (CFU-L) in 23 patients with advanced MDS and 32 patients with de novo AML. Circulating blast progenitors were identified in 74% of MDS and 81% of AML samples. Primary plating efficiencies (PE1) were similar in both disorders, despite marked differences in peripheral blast cell concentrations. By cytological and cytochemical examination, colonies from MDS patients were indistinguishable from those obtained in AML. Cell cycle status was assessed by loss of colony formation following short-term exposure to cytosine arabinoside. CFU-L suicide rates (median, range) were 40% (12% to 77%) in MDS and 60.5% (27% to 98%) in AML. Actively proliferating blast cell progenitors are thus not confined to AML, but are also present in the majority of MDS patients. An important difference between MDS and AML was found when self-renewal capacity of CFU-L was examined by means of secondary plating efficiencies (PE2). Colonies could be successfully replated in 74% of AML cases. PE2 showed marked heterogeneity (2 to 730 colonies/10(5) mononuclear cells), with some values indicating excessive self-renewal capacity of CFU-L. In contrast, 62% of the MDS specimens failed to produce any secondary colony growth, and PE2 in the remaining cases was low (5 to 99/10(5) MNC). We conclude that a different balance between self-renewal and determination could be responsible for a slower pace of clonal expansion in MDS, even if the proliferative activity of clonogenic cells is similar to that in AML. PMID- 1638021 TI - Changes in cell surface antigen expressions during proliferation and differentiation of human erythroid progenitors. AB - Cell surface antigen expression during proliferation and differentiation of human erythroid progenitors was examined using a combination of sequential micromanipulations of paired daughter cells derived from erythroid burst-forming units (BFU-E) and immuno-staining with a panel of monoclonal antibodies. Single hematopoietic progenitors were identified in methylcellulose cultures containing human cord blood mononuclear cells and micromanipulated individually to secondary culture. Paired daughter cells, granddaughter cells, and subsequent generations, whose counterparts produced erythroid bursts, were stained with various cytochemical and immuno-alkaline phosphatase stainings. Most paired daughter cells of BFU-E immunostained positively with anti-platelet glycoprotein(GP) IIb, antiplatelet GPIIb/IIIa, anti-HLA-DR, and antitransferrin receptor antibodies. Acid phosphatase staining was also positive. Neither CD34 nor CD33 antigens were identified on the cells. CD36 and blood group A antigens were first identified on cells from aggregates containing 32 to 64 cells after 4 days of secondary culture and preceded the expression of glycophorin A and hemoglobin alpha. These results indicate that various cell surface antigens were sequentially expressed during the proliferation and differentiation of erythroid progenitors, and that our procedure may be useful for clarifying the morphologic and immunologic properties of hematopoietic stem cells. PMID- 1638022 TI - Recombinant glycosylated human interleukin-6 accelerates peripheral blood platelet count recovery in radiation-induced bone marrow depression in baboons. AB - This report was aimed at confirming the potential clinical use for a genetically engineered glycosylated human interleukin-6 (rhIL-6) in hematopoiesis. Its tolerance and efficacy were assessed on hematopoietic restoration after neutron radiation-induced bone marrow injury on baboons, which represent an adequate model of parallelism for studying hematology in the human. The particular neutron radiation absorption pattern in the body allows the preservation of underexposed bone marrow areas that mimics an autotransplantation-like situation. An initial dose finding study (1 microgram up to 20 micrograms/kg/d for 8 consecutive days) in normal baboons established a dose-dependent response regarding the peripheral platelet count (range of increase, 1.5- to 4-fold). A significant elevation in white blood cell (WBC) count, as well as a substantial reversible normochromic normocytic anemia, were observed for the highest doses only (10 and 20 micrograms/kg/d). All rhIL-6 administered doses were clinically well tolerated. In myelosuppressed baboons, a selected dose of 10 micrograms/kg/d of rhIL-6 for 13 consecutive days significantly lessened the degree of induced thrombocytopenia as compared with the control group (P = .01) and shortened the time to occurrence of the nadir, showing that the onset of recovery occurs much earlier, ie, an average of 5 days (P = .003), in the treated group. Moreover, this accelerated platelet recovery is evidenced by an 8-day shorter mean time back to baseline values (P = .03) in the rhIL-6--treated animals. At this dose no effect was observed on the WBC recovery pattern. Importantly rhIL-6 did not accentuate the radiation-induced anemia and was clinically well tolerated. All tested monkeys recovered from their induced pancytopenia and no animal loss was recorded. IL-6, tumor necrosis factor, and IL-1 blood measurements are reported. In conclusion, rhIL-6 is a potent thrombopoietic factor for the treatment of induced thrombocytopenia in nonhuman primates at a clinically well-tolerated dose. PMID- 1638024 TI - C-reactive protein and beta-2 microglobulin produce a simple and powerful myeloma staging system. AB - Multiple myeloma (MM) staging procedures are still inadequate for detection of the optimal therapeutic procedure for an individual patient. The Durie & Salmon staging system and serum beta 2-microglobulin (beta 2M) are used worldwide because of their easy clinical application. Other prognostic parameters, such as myeloma cell proliferative activity, are of exceeding importance, but are not as simple as standard methods. Recently, interleukin-6 (IL-6) has been shown to be a major growth factor for MM. IL-6 is a pleiotropic cytokine acting on several cell lineages, and, at the hepatocyte level, stimulates the synthesis of acute phase proteins, such as the well known C-Reactive Protein (CRP). Serum CRP concentration actually reflects the IL-6 activity. A survival analysis carried out in 162 MM patients at diagnosis showed that serum CRP level is a highly significant prognostic factor. Moreover, serum CRP was independent of serum beta 2M. This feature allowed stratification of MM patients into 3 groups according to CRP and beta 2M serum levels: (1) low risk group, CRP and beta 2M less than 6 mg/L (50% of patients); (2) intermediate risk group, CRP or beta 2M greater than or equal to 6 mg/L (35% of patients); (3) high risk group, CRP and beta 2M greater than or equal to 6 mg/L (15% of patients). Survival was 54, 27, and 6 months, respectively (P less than .0001). We thus propose a new and powerful myeloma staging system based on simple and reliable laboratory evaluations. PMID- 1638023 TI - A defect of platelet aggregation associated with an abnormal distribution of glycoprotein IIb-IIIa complexes within the platelet: the cause of a lifelong bleeding disorder. AB - A young Italian man (A.P.) has a lifelong history of bleeding from gums and mucocutaneous tissue. Electron microscopy showed a wide diversity of platelet size including giant forms. In citrated platelet-rich plasma (PRP), platelet aggregation induced by adenosine diphosphate (ADP) and other agonists was much reduced. Both secretion and clot retraction were normal. The aggregation of washed platelets with ADP was improved but remained subnormal, as was aggregation with collagen and thrombin. Fibrinogen-binding was analyzed by flow cytometry using platelets in whole blood or PRP and was markedly decreased. Crossed immunoelectrophoresis of Triton X-100 extracts of (A.P.) platelets showed that GP IIb-IIIa levels were 40% to 50% of normal. Glycoprotein (GP) IIb and GP IIIa were of usual migration in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but their labeling was much reduced during lactoperoxidase-catalyzed iodination. Binding to (A.P.) platelets of four different 125I-labeled monoclonal antibodies to GP IIb-IIIa complexes was reduced to 12% to 20% of normal levels. However, when the patient's platelets were stimulated with alpha-thrombin, monoclonal antibody binding showed the same increase (approximately 20,000 sites) as normal platelets. Both flow cytometry and immunocytochemical studies showed that the distribution of residual surface GP IIb-IIIa within the total (A.P.) platelet population was heterogeneous and not related to platelet size. Staining of ultrathin sections confirmed the presence of an internal pool of GP IIb-IIIa. Monoclonal antibodies to other membrane glycoproteins bound normally to (A.P.) platelets. The patient has a selective deficiency of the surface pool of GP IIb IIIa complexes that is manifested clinically by a mild Glanzmann's thrombasthenia like syndrome. PMID- 1638025 TI - Absence of immunoglobulin variable region hypermutation in a large cell lymphoma after in vivo and in vitro propagation. AB - Several genetic mechanisms have been shown to diversity the expressed antibody repertoire of committed B lymphocytes. These include somatic hypermutation, V gene replacement, and ongoing gene rearrangement. These mechanisms may be operational at discrete points in the B-cell differentiation pathway and may generate idiotypic diversity in various malignant B-cell tumors. Hypermutation of the Ig variable region has been shown to occur in follicular lymphoma, but not in pre-B cell acute lymphoblastic leukemia, Burkitt's lymphoma, chronic lymphocytic leukemia, or myeloma. To study hypermutation in a large cell lymphoma, we use a polymerase chain reaction-based approach, employing consensus VH and JH primers, to clone and sequence rearranged Ig heavy chain variable regions. Neither tumor cells immortalized in rescue fusions nor idiotypic variants of a tumor-derived cell line generated through ongoing lambda light chain gene rearrangements show any significant number of variable region mutations. Thus, at the in vivo stage of B-cell differentiation from which this large cell lymphoma arose, Ig variable region hypermutation was not occurring, nor did it occur during propagation in vitro of these tumor cells. Thus, the window of hypermutation in malignant B-cell tumors is more precisely defined, which may have clinical implications for diagnostic and therapeutic approaches directed at the Ig variable region. PMID- 1638026 TI - Effect of mast cell growth factor (c-kit ligand) on clonogenic leukemic precursor cells. AB - Mast cell growth factor (MGF), the ligand for the c-kit receptor, has been shown to be a hematopoietic growth factor that preferentially stimulates the proliferation of immature hematopoietic progenitor cells (HPC). We studied the effect of MGF on the in vitro growth of clonogenic leukemic precursor cells in the presence or absence of interleukin-3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF), and/or erythropoietin (EPO). Leukemic blood and bone marrow cells from patients with various types of acute myeloid leukemia (AML), chronic myeloid leukemia (CML) in chronic phase, as well as bone marrow samples from patients with myelodysplastic syndromes (MDS) were studied. MGF as a single factor did not induce significant colony formation by clonogenic leukemic precursor cells. In the presence of IL-3 and/or GM-CSF, MGF weakly stimulated the colony formation by clonogenic precursor cells from patients with AML. In contrast, in the presence of IL-3 and/or GM-CSF, MGF strongly induced both size and number of leukemic colonies from patients with CML in chronic phase. Furthermore, in the presence of EPO, MGF strongly stimulated erythroid colony formation by CML precursor cells. Cytogenetic analysis of the colonies showed that all metaphases after 1 week of culture were derived from the leukemic clone. In patients with MDS, MGF strongly stimulated myeloid colony formation in the presence of IL-3 and/or GM-CSF (up to fourfold), and erythroid colony formation in the presence of EPO (up to eightfold). Not only the number, but also the size of the colonies increased. In the presence of MGF, the percentage of normal metaphases increased in three patients tested after 1 week of culture compared with the initial suspension, suggesting that the normal HPC were preferentially stimulated compared with the preleukemic precursor cells. In the absence of exogenous EPO and in the presence of 10% human AB serum, MGF in the presence of IL-3 and/or GM-CSF induced erythroid colony formation from normal bone marrow and patients with MDS or CML, illustrating that MGF greatly diminished the EPO requirement for erythroid differentiation. These results indicate that MGF may be a candidate as a hematopoietic growth factor to stimulate normal hematopoiesis in patients with acute myeloid leukemia, or with myelodysplastic syndromes. PMID- 1638027 TI - MYC rearrangements in histologically progressed follicular lymphomas. AB - Histologic transformation of low-grade follicular lymphoma to an aggressive-grade lymphoma occurs in 60% to 80% of patients during their clinical course. The events that drive the transformation process are poorly understood. Deregulation of the MYC gene has been implicated in a small number of cases. This observation led us to examine the molecular organization of the MYC oncogene in 38 cases of histologically transformed lymphomas that arose from follicular lymphomas, and in 18 of the initial pretransformation follicular lymphomas. In addition, we examined 58 "control" low-grade follicular lymphomas that had not yet shown evidence of histologic progression. Immunoglobulin heavy chain and light chain gene rearrangements were detected in all biopsies and rearrangements of the BCL-2 locus were seen in 36 of 38 of the transformed lymphomas (consistent with their origin from follicular lymphomas), in 18 of 18 of the pretransformation follicular lymphomas, and in 51 of 58 of the control follicular lymphomas. All 18 pretransformation follicular lymphoma specimens displayed at least one immunoglobulin gene and BCL-2 rearrangement in common with the corresponding histologically progressed lymphoma, indicating a clonal relationship between the original follicular lymphoma and the histologically transformed lymphoma. MYC rearrangements were detected in 3 of 38 (8%) transformed lymphomas and in 1 of 58 (2%) control follicular lymphomas. The latter MYC rearranged follicular lymphoma was clinically aggressive and transformed to a high-grade lymphoma that led to the death of the patient within 20 months. None of the 18 pretransformation follicular lymphomas showed MYC rearrangement, including two from patients who later demonstrated MYC rearrangement in the progressed aggressive lymphoma. PvuII mutational analysis failed to identify additional MYC gene abnormalities in the progressed lymphomas. Because the Epstein-Barr virus (EBV) is associated with a fraction of high-grade lymphomas and is known to upregulate BCL-2, we looked for a potential role for this agent in our progressed lymphomas. We did not detect viral sequences in any case indicating that EBV does not play a major role in progression. The presence of MYC rearrangements in a small fraction of progressed aggressive lymphomas, and not in the corresponding antecedent follicular lymphomas, suggests that acquisition of a MYC rearrangement is in some cases associated with the transformation event. PMID- 1638028 TI - bcl-2 gene expression in hematopoietic cell differentiation. AB - Nonrandom translocations with breakpoint at band q21 on chromosome 18 might cause bcl-2 gene deregulation and might contribute to neoplastic transformation in human lymphomas. As the pattern of expression of bcl-2 in hematopoietic cells is still unclear, we have measured the level of the corresponding messenger RNA (mRNA) in a variety of myeloid and lymphoid cell malignancies not usually associated with the t(14;18) translocation. Molecular genetic analysis showed that bcl-2 was rearranged in only 2 of 77 patients: one was affected by hairy cell leukemia and one by diffuse small cleaved cell lymphoma with peripheral blood invasion. Although in rare cases of myeloid leukemia fairly high levels can be found, the expression of bcl-2 appears to be typical of certain lymphoid malignancies. High levels of bcl-2 mRNA had been found, previously, in established pre-B-cell lines. However, in fresh specimens, the peak level of bcl 2 expression shifts to a more differentiated cell type, represented by the long living B lymphocytes that are found in most cases of chronic lymphocytic leukemia. bcl-2 gene product might have a role in prolonging cell survival and, even in the absence of translocations, might contribute to some of the biologic features that are typical of this disorder. PMID- 1638029 TI - Phagocytosis of Plasmodium falciparum-infected human red blood cells by human monocytes: involvement of immune and nonimmune determinants and dependence on parasite developmental stage. AB - The stage-dependent phagocytosis of Plasmodium falciparum-infected erythrocytes (IRBC) opsonized with nonimmune serum has been investigated. An average of 2.9 red blood cell (RBC) harboring ring-forms (RIRBC) and 7.5 RBC infected with trophozoites (TIRBC) or schizonts (SIRBC) were ingested per monocyte, in comparison with 0.8 noninfected RBC (NRBC) or 5 RBC oxidatively damaged with diamide. Abrogation of generation of complement component C3b or blockage of its binding to the phagocyte inhibited phagocytosis of RIRBC by 78% to 95% and of TIRBC by 25% to 50%. Blockage of immunoglobulin G (IgG) binding reduced phagocytosis of both RIRBC and TIRBC nonsignificantly by 14%. Preincubation of monocytes with phosphatidylserine (PS)-containing liposomes reduced phagocytosis of TIRBC by 22%, but had little effect on RIRBC. Residual, noncomplement, non-IgG , and non-PS-dependent phagocytosis amounted to 6% to 18% of total phagocytosis in RIRBC and TIRBC, respectively. RIRBC bound 2.5 times more protein A and 3.1 times more anti-C3c (a stable derivative of C3b) antibodies, and TIRBC bound 20 times more protein A and 6.8 times more anti-C3c antibodies than NRBC. Phagocytosis of oxidatively damaged RBC and RIRBC are similar, whereas a higher portion of phagocytosis appears to be noncomplement-dependent and PS-suppressible in TIRBC. It is concluded that RIRBC generate recognition signals similar to those present in oxidatively damaged or senescent RBC. Extensive membrane modifications in TIRBC produce additional, hitherto undefined signals that induce much higher and qualitatively distinct phagocytosis. PMID- 1638030 TI - Spectrin Jendouba: an alpha II/31 spectrin variant that is associated with elliptocytosis and carries a mutation distant from the dimer self-association site. AB - Spectrin Jendouba (alpha II/31) was found in a Tunisian family. In the heterozygous state, it is associated with asymptomatic elliptocytosis and a minimal defect in spectrin dimer self-association. On partial digestion of spectrin with trypsin, an abnormal cleavage appeared following Lys 788. Peptide and DNA sequencing indicated that the responsible mutation is alpha 791 Asp--- Glu (GAC----GAA). As in most alpha-spectrin variants associated with elliptocytosis, the change alters helix 3 of the proposed triple helical model of spectrin structure. Modified helix 3 in repeat alpha 8 is the most distant from the N-terminus of alpha-spectrin in known variants associated with elliptocytosis. PMID- 1638031 TI - Dynamic assessment of quality of life after autologous bone marrow transplantation. AB - To determine the quality of life in adult patients after autologous bone marrow transplantation (BMT), we administered a questionnaire to a cohort of patients seen at a single referral-based center. The sample included adults 18 years and older during the 1 year following an autologous BMT. Both disease-free patients and those who relapsed with 1-year of follow-up data available were included. Of 59 eligible patients, 58 (98%) responded to the questionnaire. Patients completed a telephone questionnaire administered by a nurse specialist in the field of BMT approximately every 90 days. At the time of initial contact on day +90, the mean quality of life was 7.8 (range, 1 to 10) on a scale of 1 to 10, with 10 being the best. By the end of the first year of follow-up, the mean quality of life was 8.9 (range, 3 to 10). Seventy-eight percent of the patients were employed. Twenty-one percent lost weight during the first year, with the majority reporting voluntary weight loss. Fourteen percent reported difficulties with sexual activity. Only 5% reported difficulty with sleeping or with frequent colds. One patient felt that her appearance was worse, and none of the patients reported a poor appetite. Eighty-eight percent of surviving adult patients reported an above-average to excellent quality of life 1 year following autologous BMT. This outcome is encouraging and suggests that this procedure is not associated with long-term morbidity in the surviving adult patient. PMID- 1638032 TI - Effect of age on human immunodeficiency virus type 1-induced changes in lymphocyte populations among persons with congenital clotting disorders. Transfusion Safety Study Group. AB - Children other than neonates infected with human immunodeficiency virus type 1 (HIV-1) have low rates of progression to acquired immunodeficiency syndrome (AIDS). Through 1989, 5.3% of 95 infected hemophiliacs aged 5 to 13 years developed AIDS, compared with 20.3% of 364 aged greater than or equal to 25 years. We asked whether the HIV-1 impact on peripheral blood mononuclear cell subpopulations differed with age using pairwise comparisons of uninfected and infected male children and adult hemophiliacs. Infected children had lesser reductions of total lymphocytes than adults, but proportionately lower numbers of CD2+, CD4+, CD2+CD26+, and CD4+CD29+ counts. CD4+CD45RA+ cell counts were greater than twofold higher in uninfected and infected children than adults; with infection, the CD4+CD45RA+/CD4+ proportion increased by 1.4-fold in adults, but was unchanged in children. Infected adults had highly significantly increased total CD8+ counts; both age groups had elevated CD8+HLA-DR+ counts. Infected children had significantly higher total B-cell counts than infected adults, with a disproportionately lower number of resting B cells (CD20+CD21+). During 2 years of follow-up, infected children and adults had lymphocyte changes in the same directions and these were proportionately equal. The lower rate of HIV-1 progression in children may be partly associated with differences in lymphocyte populations compared with adults; functional properties of immune cells may be equally or more important. PMID- 1638033 TI - Subcutaneous erythropoietin for treatment of refractory anemia in hematologic disorders. PMID- 1638034 TI - Therapy of Plasmodium falciparum parasitemia with desferrioxamine. PMID- 1638035 TI - Clonal origin of abnormal granulocytes in paroxysmal nocturnal hemoglobinuria. PMID- 1638036 TI - [Contamination of foods with chemical substances and its control]. PMID- 1638037 TI - [Behavior therapy as a new procedure in health education--recommendation for introducing behavior science into personal health services]. AB - Recent efforts to integrate biomedical and behavioral science perspectives and techniques have revealed the creativity and efficacy of behavioral health approaches to health enhancement and disease prevention. There are expectations that behavioral medicine and behavioral health will be significant in approaches toward changing life style, improving patient's compliance with medical advice, and in rehabilitation. Three examples of actual practice of behavioral procedures in a public health center are studied-behavior therapies for obesity and hypercholesterolemia, and prompting of patient clinic utilization behavior by a letter of introduction. The importance of proper selection of target problems, staff training is emphasized. In conclusion, it is recommended that behavioral science and its techniques of assessment and treatment are incorporated into public health activities, especially in the field of health education. PMID- 1638038 TI - [A study of dietary intakes and dietary preferences by questionnaire at a health facility in an urban area]. AB - Dietary preferences and intakes of 2504 patients in a human dock in Tokyo were studied by questionnaire and analyzed according to: 1. Comparison of dietary patterns for breakfast to that for lunch and dinner. 2. Consistency between dietary patterns according to Category Score Table for Breakfast and that from Hayashi's Quantification Theory Type III (QIII). Dietary patterns for breakfast were shown to fall into four Types based on dietary intakes and dietary preferences: Balanced Diet-Japanese Style (Type 1); Balanced Diet-Western Style (Type 2); Unbalanced Diet-Western Style (Type 3); and Unbalanced Diet-with drinks (Type 4). Based on the responses to the questionnaire, there was no correlation between the dietary pattern for lunch to that for breakfast. On the other hand, the dietary pattern for dinner tended to correlate with breakfast. The sample population was divided into two random groups A and B. Group A was analyzed by QIII, and B by the four types of breakfast dietary patterns. Comparison of scores for categorized values for Group A with those of the Group B indicated 91.8% consistent rate. These results, demonstrate that this questionnaire can be used effectively to sort intakes into four dietary patterns, and may be useful in preventive health care studies. PMID- 1638039 TI - [A population based survey of attendance at screenings in urban areas]. AB - To clarify the present situation of screenings in urban areas, a population based survey on attendance at screenings was conducted in Kitakyushu City. Self administered mailed questionnaires were sent to three thousand randomly selected subjects 40 years of age or over living in Kitakyushu City. The results are summarized as follows: 1. Considerable differences were observed in the number of people who were offered screenings at work sites for those between the ages of 40 59 compared to those 60 years of age or over, and between full-time employees and part-time or self-employed workers. 2. Among people who obtained stomach examinations, middle age men mainly received cancer screenings at work sites, while women or older men were mainly examined when they went to clinics or hospitals when abdominal discomforts occurred. Among women who received uterine examinations, all age groups mainly received cancer screenings at city administered screenings at clinics or hospitals, and rates decreased as age increased. 3. Among people who did not obtain stomach examinations, many middle age people wanted to be examined for stomach cancer but were unable to, while older people did not think it necessary. In the case of uterine cancer screening, middle age women did not want to receive it, while older women did not think it necessary. 4. For those people who are not offered cancer screenings at workplaces, it is assumed that those who have a positive attitude toward screening will obtain it, if offered, at sites conducted by the local government.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1638040 TI - [Studies of bacterial indicators for water pollution--growth of Escherichia coli and enterococci in limited nutrient conditions]. AB - Bacteria, that would be an ideal indicator for fecal contamination in environmental water, should not proliferate but at the same time should survive a little longer than enteropathogenic bacteria in the environmental water. While conventional methods have recommended Escherichia coli as an indicator, enterococci is recommended as a preferable indicator for the estimation of fecal contamination based on the following observation. The relationship between the specific growth rate of organism and the concentration of peptone was determined and the value of Ks, a parameter analogous to Michaelis-Menten constant, was estimated. Ks of Escherichia coli, Enterococcus faecalis and Enterococcus faecium were 3.8, 11.1 and 12.5 mg/ml respectively, indicating that Escherichia coli will grow at lower concentration of peptone than enterococci. Escherichia coli also grew in human fecal suspension and in filtrated (0.22 microns) river water, and while in those conditions enterococci did not grow or survive longer than Escherichia coli, survival time was longer than for Salmonella typhi and Shigella sonnei. It appears that enterococci reflect more accurately actual fecal contamination. PMID- 1638041 TI - [The relation between physical status, life style and subjective feeling of health]. PMID- 1638042 TI - [An index of urinary hydroxyproline (HOP) in epidemiological surveys]. PMID- 1638043 TI - The determination of low d5-phenylalanine enrichment (0.002-0.09 atom percent excess), after conversion to phenylethylamine, in relation to protein turnover studies by gas chromatography/electron ionization mass spectrometry. AB - A gas chromatography/mass spectrometry (GC/MS) method for measuring very low levels of enrichment of d5-phenylalanine (0.002-0.09 atom percent excess) is described. This method makes it possible to determine the enrichment of amino acid incorporated into tissue protein during studies of protein synthesis in man. Phenylalanine is enzymatically converted to phenylethylamine and the d5 enrichment is measured in the heptafluorobutyryl derivative by selective-ion recording under electron ionization conditions. The coefficients of variation for muscle-protein hydrolysate samples enriched with d5-phenylalanine at the 0.005 and 0.05 atom percent excess levels were 6.0 and 1.2%, respectively. This precision at low enrichment and the small amount of protein needed (about 1 mg) provide real advantages for clinical studies of tissue protein synthesis. Moreover, in contrast to the conventional approach which uses GC/MS for plasma amino acids (typically 2-20 atom percent excess) but gas isotope-ratio mass spectrometry for protein-bound amino acids, the enrichment of both plasma-free and protein-bound d5-phenylalanine can be measured with a single instrument. PMID- 1638044 TI - Ion-trap mass spectrometry applications in forensic sciences. I. Identification of morphine and cocaine in hair extracts of drug addicts. AB - Daughter-ion spectra obtained by ion-trap mass spectrometry have been successfully employed in the field of drug abuse investigation. Selection and collision-induced fragmentation of molecular-ion species of morphine and cocaine lead to an easy identification of such molecules in hair extracts of heroin and cocaine addicts. PMID- 1638045 TI - Improvements in ion-trap chemical-ionization performance. AB - Ion-trap chemical-ionization performance has been improved by application of a modified scan function for the rejection of the undesired electron-ionization like (EI-like) ions formed at the beginning of the reaction ionization period. The net effect of this software modification to the automatic reaction control is to produce chemical ionization (CI) spectra that are no longer adulterated with concentration-dependent EI-like ions. Under such improved conditions, CI spectra from an ion trap can now be directly compared with CI spectra produced on conventional quadrupole and magnet-scanning instruments. PMID- 1638046 TI - Differences in the conformational state of a zinc-finger DNA-binding protein domain occupied by zinc and copper revealed by electrospray ionization mass spectrometry. AB - Transition metal ions are important in biological regulation partly because they can bind to and stabilize protein surface domain structures in specific conformations that are involved in key molecular recognition events. There are two C2-C2 type zinc-finger sequences within the highly conserved DNA-binding domain of the estrogen receptor protein (ERDBD). Electrospray ionization (ESI) mass spectrometry has been used to demonstrate that the metal-binding sites within the 71-residue ERDBD can bind either Zn (up to 2) or Cu (up to 4). Evidence for the induction and/or stabilization of a different conformational state with bound Cu is revealed by a characteristic shift in the ESI charge envelope. The 10+ charge state is most abundant for the fully reduced ERDBD apopeptide and the ERDBD-Zn holopeptide (bound Zn does not alter the charge envelope). In contrast, the 8+ charge state is typically the optimum charge state observed for the ERDBD-Cu holopeptide; indeed, the entire charge envelope is frame-shifted to lower charge states with bound Cu. Interpretation of the altered charge states is simplified because (i) a single type of metal-binding ligand (sulfur) is involved in the case of both Zn and Cu binding, and (ii) the two different metal cations are both divalent. Thus, it is likely that the dissimilar charge envelopes represent different peptide conformers, each of which is stabilized by a different type of bound metal ion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1638047 TI - Biological stereology: history, present state, future directions. AB - The development of a quantitative structural platform for experimental biology- extending across a hierarchy of sizes ranging from molecules to organisms--has been punctuated by a series of major achievements over the last 30 years. Stereology, a form of quantitative morphology, has contributed handsomely to this success. A personal view is presented highlighting key events in the development of biological stereology. We also examine stereology with a view toward future developments in biology and speculate how stereology might contribute to the new biological infrastructure currently being built with computers. PMID- 1638048 TI - Computer-assisted morphometry: point, intersection, and profile counting and three-dimensional reconstruction. AB - The use of computers in morphometry can involve 1) automated image analysis, semiautomated image analysis and point, intersection, intercept and profile counts of two-dimensional images on tissue sections with mathematical extrapolation to the third dimension, 2) direct measurement of volumes, surfaces, lengths, and curvature using x,y,z coordinates of serial sectioned images, or 3) stereologic techniques and serial sections which is a combination of 1 and 2 above. Automated and semiautomated image analysis are generally restricted to specimens that are characterized by differential contrast such as interalveolar septa in the lung or histochemically stained mucous granules in pulmonary epithelium. Point, intersection, and profile counts using hand-held, notebook PCs, portable PCs, or standard PCs and MS-DOS-based application programs are extremely efficient, precise, affordable, and convenient methods of quantitating average values of a population. When morphometric measurements of individual structures are required, computer-assisted three-dimensional reconstruction using x,y,z coordinates of the surface outline from serial sections is a tedious yet precise method. We describe a computer program that efficiently estimates mean caliper diameter, volume, and surface area with less than five percent error with five sections per structure. We also describe a program that does digital image subtraction on serial sections, superimposes digitally generated test systems on biological images, and accumulates point, intersection, and profile counts using a Macintosh II series computer. PMID- 1638049 TI - An image processing/stereological analysis system for transmission electron microscopy. AB - This study examines the feasibility of combining computer image digitization, image enhancement, and point counting stereological techniques to quantify video images from transmission electron microscopes (TEM). The essential hardware consists of an IBM PC/AT, a Matrox imaging board, a digitizing tablet, a high resolution black and white monitor, and a portable mass storage device. In addition a video camera must be mounted to the TEM. The software is written in three modules which have numerous routines for image acquisition, enhancement, and quantification. Quantification is achieved by selecting an electronic lattice and superimposing it on the cell image. A cursor is moved on the lattice (via the digitizing tablet) and the points are entered into a spreadsheet. One of the major limitations of the system was the reduced resolution inherent in the current hardware. However, sampling experiments showed that one could compensate for the reduced resolution by increasing the magnification of the digitized images, and the stereological values from digitized images compared favorably to those from electron micrographs. Furthermore, the system proved advantageous by eliminating the usual darkroom work, and in enhancing low contrast tissue. In spite of several hardware limitations, the concept of quantifying computer digitized TEM images appears promising. PMID- 1638050 TI - The microcomputer and image analysis in diagnostic pathology. AB - This paper presents a snapshot view of the influence and direction of microcomputer technology for image analysis techniques in diagnostic pathology. Microcomputers have had considerable impact in bringing image analysis to wider application. Semi-automated tracing techniques are a simple means of providing objective data and assist in a wide range of diagnostic problems. From the common theme of reducing subjectivity in diagnostic assessment, an extensive body of research has accrued. Some studies have addressed the need for quality control for reliable, routine application. Video digitizer cards bring digital image analysis within the reach of laboratory budgets, providing powerful tools for investigation of a wide range of cellular and tissue features. The use of staining procedures compatible with quantitative evaluation has become equally important. As well as assisting scene segmentation, cytochemical and immunochemical staining techniques relate the data to biological processes. With the present state of the art, practical use of microcomputer based image analysis is impaired by limitations of information extraction and specimen throughput. Recent advances in colour video imaging provide an extra dimension in the analysis of multi-spectral stains. Improvements will also be felt with predictable increase in speed of microprocessors, and with single chip devices which deliver video rate processing. If the full potential of this hardware is realized, high-speed, routine analysis becomes feasible. In addition, a microcomputer imaging system can play host to companion functions, such as image archiving and transmission. With this outlook, the use of microcomputers for image analysis in diagnostic pathology is certain to increase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1638051 TI - Quantitative perimeter and area measurements of digital images. AB - Quantitative estimations of perimeter and area from digitized video images, and the application of these features in morphometry, are discussed. Estimations from manual tracings via interactive peripherals and from chain codes are addressed. Topics discussed are calibration, determination of vertical and horizontal pixel resolution, effects of tracing jitter, and for chain codes, the spatial quantization scheme representation of the digital contour. Finally, new perimeter estimators for 4-connected and 8-connected chain codes for non-unity pixel aspect ratio are presented with simulation results. PMID- 1638052 TI - Quantitative morphology for biologists and computer scientists: I. Computer-aided tutorial for biological stereology (version 1.0). AB - This paper describes a computer-aided tutorial for biological stereology. Stereology, a type of quantitative morphology, includes a collection of statistical methods that quantify the structural compartments that can be viewed in sections with light and electron microscopy. These methods provide volume, surface, length, shape, and number data, and help define the quantitative relationships among the structural compartments of biological hierarchies. Hierarchies, which connect structural data ranging in size from molecules to organs, serve as a central core to which the data of biological databases can be linked. The tutorial focuses on two objectives. It provides the user primarily interested in using quantitative morphology databases with background information, and offers a set of state-of-the-art tools to researchers wishing to use these methods in the laboratory. The main topics of the tutorial include: introduction to quantitative morphology, symbols/terms, data types, sampling, hierarchies, data interpretation, and utilities. The tutorial runs under the MS DOS operating system and requires at least an IBM PC AT (or compatible), a color monitor (EGA, VGA), 540 KB of RAM, and 3 MB of hard disk space. PMID- 1638053 TI - Computer assisted data collection for stereology: rationale and description of point counting stereology (PCS) software. AB - The paper describes microcomputer software for point counting stereology. Stereology includes a collection of statistical methods that quantify the images of light and transmission electron microscopy. The methods use test grids placed over images to collect raw data, which includes counts of points, intersections, transections, and profiles. In turn, the counts are included in stereological equations that give estimates of compartmental volumes, surfaces, lengths, or numbers. These parameters describe the composition of a structure in three dimensional space. The PCS (point counting stereology) System Software III serves as a data collection, storage, and management tool. Users set up point counting protocols without programming, enter data by pressing predefined function (MS DOS) or alphabetic keys (UNIX), store data in files, select files for analysis, and calculate results as stereological densities. The latest version of the PCS software includes a new user interface and is designed as a research "front end" that can feed data either into the calculation tools of a stereology tutorial (Bolender, 1992, this issue) or into the analysis routines of quantitative morphology databases (Bolender and Bluhm, 1992). PMID- 1638054 TI - A new procedure for handling impervious biological specimens. AB - A new application of techniques for preparing impervious biological specimens for light microscopy (LM) and transmission electron microscopy (TEM) has been developed. Microwave irradiation was used to facilitate fixation. A priming technique was used to increase the bonding of the outer surface of the specimens with the resin. Priming the waxy or cuticular surface with Z-6040 (gamma glycidoxypropyl trimethoxysilane) solved the problem of specimen "pull out" from the resin. Insect specimens with various types of cuticles (waxy or chitinous) and seeds were successfully studied ultrastructurally using this technique. PMID- 1638055 TI - The influence of lens chromatic aberration on electron energy-loss spectroscopy quantitative measurements. AB - An investigation has been made into the effect of chromatic aberrations of a pre spectrometer lens system on quantitative elemental analysis by electron energy loss spectroscopy (EELS). In transmission electron microscopy (TEM) diffraction mode, the measured effects are typically 150-330 times larger than if only objective-lens chromatic aberration were important. We discuss several methods of avoiding errors arising from chromatic aberration, including selection of a suitable optical mode (dependent on the desired spatial resolution), adjustment of the TEM imaging system so as to focus the system for a chosen energy loss, and analysis of a large area of a uniform specimen. PMID- 1638056 TI - [Cytochemical ultrastructural study of adenosine 5'monophosphate hydrolysis in human spermatozoa]. AB - A specific 5'nucleotidase activity (pH 7.4) is localized by cytochemical technics, in the head (nuclear membrane, periacrosomal cytoplasm) and in the mitochondrial membrane of human spermatozoa. The effect of different effectors (manganese, nickel, fluoride, tartrate, tetramisole), studied in the head by rate assessment of cells with or without hydrolysis sites, changes the cellular distribution, the depth of reactions and their localization. The 5'nucleotidase interferences with some unspecific phosphatases are discussed. PMID- 1638057 TI - Morphology, distribution and types of valves in the adult male's testicular veins. AB - Morphologically, the pampiniform plexuses investigated had, in their majority, no vascular spiraling on the left side, the same occurring on the right side; however, as for the total number of valves, except for those of the pampiniform plexuses, the left side was found contain a greater number of valves. As regards valve types, there is a predominance of double semilunar one on both sides rather than single semilunar valves. PMID- 1638058 TI - [DIfferentiation of enthesis and the synovial membrane in the rat]. AB - The development of the knee joint in Wistar rats was observed from the 14th fetal day to the 40th postnatal day by light microscopy, transmission electron microscopy and scanning electron microscopy. The differentiation of the capsular ligamentous and tendinous attachments, synovial cavity, and A and B cells were particularly compared. Capsular attachments appeared for the first time at the 15th day of fetal life. The formation of the cavity started at the 17th day of fetal life. The differentiation of A and B cells was observed by the 20th fetal day by T.E.M., and only by the 15th postnatal day by S.E.M. PMID- 1638059 TI - [Anatomy and physiology of the muscles in cleft lip and palate]. AB - The authors present the anatomy and the physiology of the normal and pathological muscles of the cleft lip and palate. The authors insist not only on the anatomic defects but mainly on the muscle functions which are the most disturbed. The purpose of this study is to guide the surgical technique in order to improve not only the cosmetic but the functional results as well. PMID- 1638060 TI - [Gracilis muscle in man]. AB - This study is based upon the dissection of 84 gracilis muscles in 42 cadavers. It allowed to emphasize the following features: 1-The proximal insertion of the muscle is a strong tendinous lamina arising from the anterior aspect of the pubis and from the ischio-pubic branch; the distal insertion to the tibia is common to both the gracilis and the semi-tendinous muscles. 2-The distal tendon of the gracilis is tightly connected to the posterior branch of the internal saphenous nerve which crosses the muscle behind the medial femoral condyle. 3-The arterial supply (52 dissections) appears to be very rich, consisting in various pedicles entering the muscle by is lateral side. The main neurovascular bundle is issued from the profound vessels of the thigh, coming either from the adductors artery (73%), either from the medial circumflex artery (19.2%), either from both networks (7.7%). The site of penetration of the vessels in the muscle is remarkably constant. The remaining pedicles (2 to 4, one of which is quite constant at the musculotendinous junction) arise from the muscular branches of the femoral artery. 4-There is a good correlation between the measured length of the muscle and the distance between the superior aspect of the pubic arch and the medial epicondyle. A 0.37 corrective factor applied to this latter distance allows to determine the exact sit of penetration of the main neurovascular bundle in the muscle. PMID- 1638061 TI - [Study of cells harvested in nasal secretions after lavage. Improvement of the cytologic technique and application to ORL and bronchial pathology]. AB - The study of the cells found in the nasal lavage fluid is now a very used method. It has many advantages and it is better than the study of nasal smears obtained by nose blowing and/or swabbing. In this work, we have studied the nasal cytology of patients with a nasal or bronchial pathology. A count of inflammatory cells in a hemocytometer is performed in 301 noses then the percentage of various cell types (eosinophils, lymphocytes and neutrophils) is performed on a glass slide stained by May Grunwald Giemsa. The results are correlated with the literature. The patients with a known NARES have a mean nasal eosinophilia of 26.8%; in the allergic rhinitis, the eosinophilia is 41.4%; the patients with a Fernand Widal Syndrome or with a nasosinusal polyposis have respectively a eosinophil percentage of 24.2% and 18.8%. PMID- 1638062 TI - [A study of the cranio-pharyngo-mandibular space by sections at low temperature]. AB - After acrylic injections into the vessels and mandibular block anaesthesia the pterygo-mandibular space is studied in 38 anatomical pieces. 538 colour slides have been obtained from anatomical cuts at low temperature with the scannigraph system. The results point out that a cranio-pharyngo-mandibular space is clearly distinguished laterally, from a medial maxillo-pharyngeal space. There is no transversal communication between them. On the contrary, the cranio-pharyngo mandibular space communicates, forward and upward, with the temporal space; forward and downward, with the sub-mandibular space. The cranio-pharyngo mandibular space contains an interpterygoid space communicating with the oval foramen by a "chimney" largely filled by the emissary pterygoid veins. A pericondilar plexus of veins is also observed. The cranio-pharyngo-mandibular space is characterised by the cellulo-adipose tissue by which it is filled and which guides the diffusion of injected solutions to the oval foramen. PMID- 1638063 TI - Variations of the blood supply of the human conus arteriosus. AB - The conus arteriosus was divided into right and left halves and each half was subdivided into 3 portions: superior, middle and inferior. The study of the blood supply of the conus was performed in 8O human hearts. The results showed that the sternocostal wall of the conus arteriosus may be supplied by the arteria coni arteriosi but, more frequently by branches of the right and left coronary arteries. The most frequent branches supplying the conus arteriosus were the ramus anterior ventriculi dextri medialis and lateralis (85%), ramus coni arteriosi dexter (51.2%), ramus anterior ventriculi dextri medius I (47.5%), ramus anterior ventriculi dextri intermedius (41.2%), ramus coni arteriosi sinister (40%) and ramus anterior ventriculi dextri superior I (38.7%). PMID- 1638064 TI - Research support supports research support. PMID- 1638065 TI - Expression of adhesion molecules in early allergic patch test reactions. AB - In order to study the relevance of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and endothelial leukocyte adhesion molecule 1 (ELAM-1) for lymphocyte extravasation in the early phase of allergic contact dermatitis, the time courses of lymphocyte infiltration and adhesion molecule expression during initiation of this disorder were determined. Sequential biopsies of positive allergic patch test reactions were obtained 4, 8, 16 and 24 h after antigen application, cryostat sectioned and stained with monoclonal antibodies for ICAM-1, VCAM-1, ELAM-1 and lymphocytes by use of an immunoperoxidase technique. The slides were evaluated semiquantitatively according to appropriate gradation scales that had been defined separately for the staining with each antibody. Our results show that there is a significant upregulation of VCAM-1 and ELAM-1 expression within the first 8 h after antigen application, when lymphocyte extravasation is just beginning. In contrast, ICAM-1 is already expressed in higher levels in normal skin and is hardly enhanced during the first 8 h of patch test reactions. The main influx of lymphocytes occurs 16-24 h after antigen application and is accompanied by a further increase in all three adhesion molecules. We conclude that VCAM-1 and ELAM-1 rather than ICAM-1 may be of particular importance for the start phase of allergic contact dermatitis and that all three of them contribute to an amplification of this inflammation. PMID- 1638066 TI - Sterile transient neonatal pustulosis is a precocious form of erythema toxicum neonatorum. AB - A sterile pustular skin eruption was observed in 17 of 3,541 newborn infants examined over a period of 30 months. The skin eruption was always present at birth and fulfilled the clinical criteria of transient neonatal pustular melanosis (TNPM). However, some days after birth, all of them but 1 developed skin lesions typical of erythema toxicum neonatorum (ETN). Histological examination of 11 biopsies obtained at the age of 1 day showed intracorneal neutrophilic pustules in 4 and subcorneal intraepidermic eosinophilic pustules in 7. On the basis of our findings and a literature review we consider that a clear cut differentiation between TNPM and ETN is not always possible. We propose the name sterile transient neonatal pustulosis to unify these conditions. PMID- 1638067 TI - Rapid diagnosis of Chlamydia trachomatis in male patients by antigen detection in urine samples. AB - To investigate the diagnostic value of testing urine samples as a rapid method for the detection of chlamydial antigen in males, first-catch urine (FCU) and urethral swab samples were obtained from 668 male patients and examined by an enzyme immunosorbent assay (EIA). Positive results were further analyzed by direct fluorescence antibody tests of the EIA sediment. Antigen detection was possible in 12.7% out of the urethra, in 10.8% out of FCU and in a total of 14.5% of the tested persons. Testing only FCU would have missed chlamydia detection in 25 (25.8%) out of a total of 97 chlamydia-positive males. Testing only genital samples would have missed 12 positive cases (12.4%). The sensitivity and specificity of the EIA test of FCU as compared with urethral swabs were 70.6 and 97.9%, respectively, and differed between urine collected before (sensitivity: 84%; specificity: 98.6%) and after (sensitivity: 65%; specificity: 97.7%; p = 0.1254) urethral sampling. The quantitative evaluation of the EIA results demonstrates that the mean value of the extinction rates was highest in specimens corresponding to a positive result from both sampling sites. This study indicates that the chlamydial detection rate was lower in FCU than in urethral samples. FCU testing may be suitable when urethral sampling is not possible; due to its high rate of unconfirmed borderline extinction, positive results should be confirmed with another chlamydial antigen detection test such as direct immunofluorescence. PMID- 1638068 TI - Desmoplastic melanoma: clinicopathologic aspects of six cases. AB - We report 6 cases of desmoplastic melanoma. Upon removal and histologic examination, each lesion consisted of a dermal nodule of fascicles of spindle cells, many of which showed pleomorphic and hyperchromatic nuclei. Fascicles, as well as single cells, were seen infiltrating the dermal collagen. Lentiginous hyperplasia of melanocytes with varying but usually slight cellular atypia overlay the dermal proliferations in all cases. Melanophages and some pigmented cells, albeit few in number, were present in the infiltrate, whereas mitotic figures were also noted. These features are most consistent with desmoplastic melanoma, a rare tumor of which a limited number of cases has been described. The clinical and histopathologic features of the lesions presented exemplify the diagnostic and therapeutic dilemma associated with desmoplastic melanoma. PMID- 1638069 TI - Microscopic evaluation of the dansyl chloride test. AB - The classical dansyl chloride test relies on visual assessment of the extinction of fluorescence in time. We introduce a microscopic and morphometric rating of this test. We show that soaps may remove the fluorescing dye from corneocytes. Therefore caution should be taken in interpreting fluorescence extinction only as an estimate of the stratum corneum renewal. PMID- 1638070 TI - Steroid-induced dermal thinning: discontinuous application of clobetasol-17 propionate ointment. AB - The skin thinning effect of discontinuous topical clobetasol-17-propionate applications was tested in human volunteers. Application frequencies were daily (1/0), every third day (1/2), every fifth day (1/4), every seventh day (1/6) and every ninth day (1/8). Clobetasol-17-propionate was administered topically under occlusion for 1 h. The treatment period was 41 days. There were no differences of the skin thinning effect of daily and 1/2 administration. The skin thinning effect of 1/4, 1/6 and 1/8 was smaller but also significant compared to controls. The curves demonstrating skin thinning effects initially were dropping off and reached a plateau within about 2 weeks. After finishing application, skin thickness normalized within 2 weeks. Because of these findings, a treatment interval of 3 days is discussed as therapeutically efficient. PMID- 1638071 TI - Malignant melanoma in 20-MHz B scan sonography. AB - In order to assess the value of 20-MHz sonography in the pre-operative diagnosis of malignant melanomas, 54 melanomas were examined. The pre-operative ultrasound scans were compared with corresponding histological sections from the excised tumours. A computer-aided measurement of the tumour thickness (sonometry) and the internal echo density (densitometry) was performed in the ultrasound scans. The melanomas appeared as largely echolucent zones. There was a significant correlation between the tumour thickness measured in the ultrasound scan and those measured in the histological sections (r = 0.938, p less than 0.001). As a rule the tumour thickness determined by sonometry were greater than the histometrically determined values. Subtumoral inflammatory infiltrate and other hypo-echoic structures in the region of the tumour are possible causes of the discrepancies. Some of those hypo-echoic structures can be identified and disregarded in B scan measurement. Even if a definite differential diagnosis is not possible on the basis of the ultrasound scan alone, 20-MHz sonography provides additional information which can be of use in surgical planning. PMID- 1638072 TI - Familial supernumerary nipples and breasts. AB - We report 3 cases of supernumerary breasts in the same family. The presence of glandular tissue (polymastia) was demonstrated by ultrasound examination. No associated kidney lesions were found. PMID- 1638073 TI - Bilateral segmental neurofibromatosis. AB - Neurofibromatosis (NF) is a heterogeneous disorder clinically characterized by the presence of neurofibromas, multiple cafe au lait spots, intertriginous freckles and Lisch nodules. We describe an unusual case of NF with cutaneous neurofibromas localized on the anterior chest, in a bilateral dermatomal distribution. No other signs were detected. The family history was negative for NF. The different subsets of NF are briefly discussed, with particular emphasis on the segmental type. PMID- 1638074 TI - Cutaneous lymphadenoma: report of 2 cases. AB - Cutaneous lymphadenoma is a recently described tumor with a distinctive histological picture associating a basaloid epithelial proliferation and intraepithelial lymphocytes; it seems to represent a benign adnexal neoplasm of uncertain histogenesis. We documented 2 additional examples of cutaneous lymphadenoma with typical histological features; the contiguity of some tumor lobules with preexisting follicular structures was noted. In 1 case, a cutaneous osteoma was present below the tumor. On immunostainings, S-100 protein revealed numerous dendritic intraepithelial and stromal cells. The basaloid proliferation was positive for broad-spectrum keratin antibodies, but negative for KL1 antibody. In addition, several areas were positive for involucrin within tumor lobules. Our findings are consistent with a pilosebaceous origin of cutaneous lymphadenoma. PMID- 1638075 TI - Menkes' disease: report of a case and determination of eumelanin and pheomelanin in hypopigmented hair. AB - We report a male infant with Menkes' disease who showed, at the age of 3 months, slow growth, hair abnormalities such as pili torti and white hair, and low levels of serum copper and ceruloplasmin. The exceptionally bright portions of his hair contained eumelanin and pheomelanin at levels only half those of normal Japanese controls. After subcutaneous administration of copper-histidinate for 2 months, his scalp hair changed to dark brown. PMID- 1638077 TI - May calcitonin spray cause nasal deformation? PMID- 1638076 TI - Evidence for CD8+ cell increase in long-term PUVA-treated psoriatic patients after PUVA discontinuation. AB - Long-term PUVA-treated psoriatic patients given maintenance therapy (UVA doses greater than 1,000 J/cm2) have been demonstrated to undergo lymphopenia and a decrease in the total number of circulating CD3+ and CD4+ T cells. The aim of this study was to assess whether the impairment of T cells is detectable also in psoriatic patients after long-lasting PUVA discontinuation. A group of 34 psoriatic patients (25 males, 9 females; mean age 52.7 +/- 12.82 years), who had previously been treated by PUVA therapy (average cumulative dose 1,898.48 +/- 1,207.12 J/cm2), was studied 1 year or more after discontinuation of PUVA therapy. The patients studied failed to show any impairment in CD3+ and CD4+ cells. Nevertheless, a significant increase (p less than 0.05) in circulating CD8+ cells (both in the percentage and the total number) was detectable in PUVA patients as compared to appropriate controls. The significance and implications of this finding are not known and need further investigations. PMID- 1638078 TI - Systemic reaction during a dansyl chloride test. PMID- 1638079 TI - Bullous and erosive stomatitis induced by nimesulide. PMID- 1638080 TI - A probable mechanism for hyperpigmentation by fotemustine. PMID- 1638081 TI - Survival in pemphigus. PMID- 1638082 TI - Unresponsiveness to etretinate during anticonvulsant therapy. PMID- 1638083 TI - Skin cancers and HLA frequencies in renal transplant recipients. AB - An association between HLA DR7 and the development of multiple non-melanoma skin cancer was detected in immunosuppressed patients in southern Australia. The relative risk was 2.6 which was lower than for immunocompetent patients with the same skin cancers. HLA frequencies of renal transplant recipients with multiple skin cancers were determined. The types HLA B27 and HLA Dr7 were found in significantly higher frequency, and there was no absence of HLA A11. PMID- 1638084 TI - Confirmation of the influence of a chromosome 7 locus on susceptibility to audiogenic seizures. AB - Mouse strain differences in susceptibility to audiogenic seizures (AGS) are due to allelic differences at multiple genetic loci. Three loci that influence susceptibility to AGS have been mapped on Chromosomes (Chr) 12, 4, and 7 (Asp-1, Asp-2, and Asp-3, respectively). Here we report evidence that confirms linkage of Asp-3 to c on Chr 7 and parental effects on AGS susceptibility, but not genomic imprinting of Asp-3. PMID- 1638085 TI - Characterization of murine carcinoembryonic antigen gene family members. AB - The carcinoembryonic antigen (CEA) is a human tumor marker whose gene belongs to a family with more than 20 members. This gene family codes for a group of proteins with in vitro cell adhesion properties and for a group of abundantly expressed pregnancy-specific glycoproteins (PSG) with unknown functions. As a basis for in vivo functional studies, we have started to analyze the murine CEA gene family and have identified five new members (Cea-2 to Cea-6). cDNA clones were isolated for Cea-2, Cea-3, and Cea-6. The deduced amino acid sequences of Cea-2 and Cea-6 indicate three IgV-like (N), followed by one IgC-like (A) domain (N1-N2-N3-A). We have also partially characterized the Cea-2 gene and two additional ones, Cea-4 and Cea-5. Cea-2 and Cea-4 are separated by only 16 kb, suggesting a close linkage of murine CEA-related genes, as found for the human CEA gene family. Cea-5 was located to the proximal region of mouse Chromosome (Chr) 7, which is syntenic to part of human Chr 19, containing the human CEA gene family cluster. Cea-2, Cea-3, and a Cea-4-like gene are differentially transcribed in the placenta during pregnancy, but not in other organs tested. This expression pattern strongly suggests that they represent counterparts of the human PSG subgroup members, despite the presence of multiple IgV-like domains, a feature not found for human PSGs. The more distantly related Cea-5 seems to be ubiquitously expressed. The putative promoter region of Cea-2 lacks typical TATA- or CAAT-boxes, but contains other conserved motifs that could play a role in the initiation of transcription. PMID- 1638086 TI - The mouse male germ cell-specific gene Tpx-1: molecular structure, mode of expression in spermatogenesis, and sequence similarity to two non-mammalian genes. AB - Tpx-1 is a testis-specific gene that maps on mouse Chromosome (Chr) 17. The deduced TPX-1 protein shows 55% amino acid sequence similarity to acidic epididymal glycoprotein (AEG), assumed to be involved in sperm maturation. In the present study, we determined the genomic structure of the mouse Tpx-1 gene and the cellular localization of its transcripts. The gene was found to contain ten exons, with an unusually large intron (approximately 17.0 kilobase pairs) between exons 8 and 9. In situ hybridization of testicular sections showed that Tpx-1 is transcribed abundantly by haploid male germ cells. A computer search of protein databases revealed that deduced TPX-1/AEG proteins have significant sequence similarity (approximately 30%) to two non-mammalian proteins: "pathogenesis related" proteins 1 of tobaccos, and venom sac proteins of white-face hornets, known as Dol m V. Amino acid residues encoded by exon 10 of the Tpx-1 gene and most of those encoded by exon 9 were absent in the non-mammalian proteins. This result suggests that the ancestor of Tpx-1 acquired exons 9 and 10 after its divergence from the ancestors of the plant and insect proteins. PMID- 1638087 TI - Cross-species conservation of a polymorphic dinucleotide repeat in the dystrophin gene. PMID- 1638088 TI - Brain beta spectrin isoform 235 (Spnb-2) maps to mouse chromosome 11. PMID- 1638089 TI - A novel polymorphism near the mouse Int-2 locus. PMID- 1638090 TI - Peroxyoxalate chemiluminescence detection of condensates of malondialdehyde with thiobarbituric acids using a flow system. AB - The peroxyoxalate chemiluminescence(CL) detection method for the evaluation of the CL intensity of malondialdehyde(MDA) condensates with seven 2-thiobarbituric acid derivatives is described. The method consists of a flow injection technique together with a CL detection system using bis(2,4,6-trichlorophenyl) oxalate(TCPO) and hydrogen peroxide as chemiluminogenic reagents. Linear correlations between CL intensity and concentration are obtained for pmol levels of condensates. Among the condensates, 1,3-diethyl-2-thiobarbituric acid(DETBA) MDA shows the largest CL intensity. High performance liquid chromatography (HPLC)/CL detection of DETBA-MDA and 1,3-diphenyl-2-thiobarbituric acid(DPTBA) MDA using a mixture of TCPO and hydrogen peroxide in acetonitrile as a postcolumn reagent solution is also described. The detection limits for DETBA-MDA and DPTBA MDA are 20 and 200 fmol, respectively, per 20 microL injection at a signal-to noise ratio of 2. This HPLC/CL detection system was applied to the determination of MDA in rat brains by using DETBA as a fluorescent derivatizing reagent. PMID- 1638091 TI - High performance liquid chromatographic determination of 1,5-anhydroglucitol in human plasma for diagnosis of diabetes mellitus. AB - This paper describes a high performance liquid chromatographic (HPLC) method for determining 1,5-anhydroglucitol in plasma, in which anion exchange chromatography and pulsed amperometric detection are used. Plasma samples deproteinized with trichloroacetic acid are passed through a three-layer column packed with (1) strongly basic anion (BO3(3-) form, the upper layer), (2) strongly basic anion (OH- form, the middle layer) and (3) strongly acidic cation (H+ form, the lower layer) exchange resins. 1,5-Anhydroglucitol is efficiently recovered in the flow through fraction and interfering substances are completely removed by the column treatment. The analytical response of the method is linear with concentration to 40 mg/L, and it is possible to detect as little as 0.1 mg 1,5-anhydroglucitol per litre of plasma. Analytical recovery is between 96 and 103%, and there is good agreement between the results measured by our method and by a gas/liquid chromatographic method (r = 0.998). The method has been successfully used for the determination of very low 1,5-anhydroglucitol concentrations (less than 1 mg/L) in the plasma of diabetic patients. PMID- 1638092 TI - Combined application of analytical high performance thin layer chromatography and electroblotting for the detection of anti-ganglioside antibodies in human sera. AB - Antibodies against gangliosides isolated from small tumour and nervous tissue specimens can be reliably detected in serum samples by the ganglioside electrotransfer technique without the need for previous purification steps. After separation by high performance thin layer chromatography gangliosides are transferred from silica gel plates to hydrophobic polyvinylidene difluoride membranes. These membranes are highly suitable for immunostaining. The use of a 15-slit device allows simultaneous testing of up to 15 serum samples. Samples of serum from 39 patients with clear-cell carcinoma of the kidney, mammary carcinoma, ovarian carcinoma and neurological disorders together with samples from healthy controls were tested for anti-ganglioside antibodies from various tissues. PMID- 1638093 TI - Phosphotungstate as a useful eluent for hepatitis-B virus surface antigen purification by heparin-sepharose affinity chromatography. AB - On the basis of the heparin-like effect of phosphotungstate (PTA), we have shown that it is useful for the purification of hepatitis-B virus surface antigen (HBsAg) using heparin-Sepharose affinity chromatography. HBsAg was eluted with 0.2-0.6 M NaCl. HBsAg was also eluted with PTA at approximately 1 mM, and the HBsAg fraction thus obtained contained fewer impurities than the corresponding fraction eluted with NaCl. Moreover, PTA yielded HBsAg and hepatitis-B virus e antigen simultaneously. PTA may specifically reduce the affinity of HBsAg for heparin as well as simply competing with heparin for an anion-binding site of HBsAg. Residual PTA in the eluate was easily decomposed by alkalization, which was useful for subsequent studies. PMID- 1638094 TI - The combination of normal phase with reversed phase high performance liquid chromatography for the analysis of asparagine-linked neutral oligosaccharides labelled with p-aminobenzoic ethyl ester. AB - We have developed a novel approach for the analysis of asparagine-linked neutral oligosaccharides derived from glycoproteins. The oligosaccharides are labelled with p-aminobenzoic ethyl ester and the derivatives are separated on two high performance liquid chromatographic columns, one containing amide-silica and the other containing octadecyl-silica. The elution positions of 39 different ABEE oligosaccharides on the two columns were plotted on a two-dimensional map. Unique non-overlapping positions of these oligosaccharides demonstrate that this technology would be useful for the identification of Asn-linked oligosaccharides at high sensitivity. PMID- 1638095 TI - A universal peroxyoxalate-chemiluminescence detection system for mobile phases of differing pH. AB - A universal peroxyoxalate-chemiluminescence detection system for high performance liquid chromatography, available for a variety of mobile phases, has been developed. The system consisted of a dual-head short-stroke pump and a chemiluminescence detector. The standard conditions using bis(2,4,6 trichlorophenyl) oxalate (TCPO) as aryl oxalate were as follows. The first postcolumn solution was the mixture of 0.5 M imidazole-nitric acid (pH 7.5) and acetonitrile (1:4, v/v). The second was acetonitrile containing TCPO-hydrogen peroxide. These two solutions were delivered by the two pump-heads. After the pH of the column eluate was adjusted to the optimum range (6.5-7.5) by the first postcolumn solution, the solution was mixed with the second postcolumn solution. After flowing through a reaction coil, the chemiluminescence of the mixture was monitored. Using this system, a high sensitivity (fmol level) was obtained for perylene as an analyte with mobile phases having different pH values (2.0-8.0). Polycyclic aromatic hydrocarbons became detectable to a high sensitivity even after the column separation using an acidic mobile phase. The detection sensitivity of nitrated pyrenes after on-line electrochemical reduction using an acidic mobile phase was also increased. This system might be available for other aryl oxalates by some modifications of the postcolumn solutions. PMID- 1638096 TI - Determination of panaxadiol and panaxatriol in ginseng and its preparations by capillary supercritical fluid chromatography (SFC). AB - Capillary supercritical fluid chromatographic (SFC) method has been developed for the determination of panaxadiol and panaxatriol in ginseng and its preparations. 0.1 g ginseng or an appropriate amount of its preparations was hydrolysed by 15% H2SO4 in an ethanol:water (1:1 v/v) solution for 4 h followed by 15% NaOH for 0.5 h. The mixture was extracted by cyclohexane. The cyclohexane extracts were purified by a partition column and concentrated by an adsorption column and then analysed by SFC. Methyltestosterone was used as the internal standard. PMID- 1638097 TI - Simultaneous determination of paraquat and diquat in serum using capillary electrophoresis. AB - The use of capillary electrophoresis for simultaneous separation and detection of the two bipyridylium herbicides, paraquat and diquat, was investigated. Both herbicides were extracted from fortified sera with disposable ODS-silica cartridges. Separation was carried out using a capillary tube (50 microns i.d., 750 mm) of fused silica containing 10 mM glycine-HCl buffer (pH 3.0), 40 mM NaCl and 20% methanol as the carrier. Paraquat and diquat were completely separated in 10 min at an applied potential of 20 kV. On-column UV monitoring allowed detection of both herbicides simultaneously. The assay sensitivity was 0.05 micrograms/mL (signal-to-noise ratio, 2:1), which probably increases with increase in the sample volume of serum. Analytical recovery of both herbicides added to serum was about 97% at concentrations of 0.5-2.0 micrograms/mL. PMID- 1638098 TI - Membrane affinity chromatography used for the separation of trypsin inhibitor. AB - Polysulphone (PS) was chemically modified by acrylation-amination and by chloromethylation-amination, respectively. An ultrafiltration membrane of chemically modified polysulphone (CMPS) was prepared by the phase inversion method. Trypsin was then covalently bonded onto the CMPS membrane by diazotization. The activity of immobilized trypsin reaches up to 10200 U/g; 15 mg trypsin was immobilized on 1 g CMPS membrane. Separation of soybean trypsin inhibitor was carried out on the affinity membrane, yielding 6.5 mg pure trypsin inhibitor in one run. The enzyme membrane has good activity and stability. PMID- 1638099 TI - Rapid chiral separation of metoprolol in plasma--application to the pharmacokinetics/pharmacodynamics of metoprolol enantiomers in the conscious goat. AB - The plasma concentrations of metoprolol enantiomers have been determined by means of a direct phenyl carbamate-cellulose-based chiral high performance liquid chromatography assay using fluorimetric detection. This assay has been used to investigate the pharmacokinetics and pharmacodynamics of metoprolol enantiomers in the conscious goat. There is evidence that the pharmacokinetics of metoprolol in the goat occurs stereoselectively and that enantiomer-enantiomer pharmacokinetic interactions occur. R-Metoprolol is less effective in reducing the mean arterial blood pressure than S- and R/S-metoprolol. PMID- 1638100 TI - Pupillary responses and blink reflex in myotonic dystrophy. AB - We have studied pupillary responses to parasympathetic and sympathomimetic agents, pupillary cycle time and the electrophysiology of the blink reflex in 18 patients with myotonic dystrophy. The response of the iris to dilute pilocarpine and phenylephrine did not indicate pharmacologic supersensitivity. Pupillary cycle time was prolonged in nine of the 18 patients. Ipsilateral R1 blink reflex latencies were normal in all cases, and bilateral R2 were normal in 16 of the 18 patients. These results do not support either autonomic or brainstem dysfunction in the majority of patients with myotonic dystrophy. In 50% of the patients the results are compatible with smooth muscle involvement of the iris. PMID- 1638101 TI - Positive pressure on neck reduces baroreflex response to apnoea. AB - This study was designed to evaluate the arterial blood pressure and heart rate responses to positive pressure applied to the neck during repetitive inspiratory apnoea. Twenty-five subjects (aged 20-40 years) were trained to exert a positive pressure on the neck by actively contracting the neck muscles and pressing the chin in the jugular notch. Blood pressure and heart rate were evaluated during 5 min long periods at rest, at the beginning and end of a 25-min period of apnoea with and without positive pressure and after a second period of rest. Positive pressure diminished the initial hypotensive and bradycardiac reactions to apnoea and augmented the heart rate and blood pressure increase towards the end of apnoea. Both systolic and diastolic pressures and heart rate were significantly elevated during both apnoeic sequences, and also remained significantly elevated after the release of pressure. Spectral analysis (FFT) and auto-regressive model showed the entrainment of the slow 0.03 Hz oscillations by repetitive apnoea and the occurrence of 0.1 Hz and respiratory 0.2 Hz components in the heart rate and blood pressure in both types of apnoea. It is suggested, since the positive pressure decreases the baroreflex and the increased sympathetic tone persists after apnoea, that such effects may contribute to the development of cardiac complications in prediposed individuals with obstructive apnoea syndrome. PMID- 1638102 TI - In vivo studies on receptor pharmacology of the human eccrine sweat gland. AB - The receptor pharmacology of the human sweat gland was studied in vivo. The axon reflex response was mediated by nicotinic receptors which were activated by nicotine and acetylcholine, but not pilocarpine, and inhibited by hexamethonium. The direct response was mainly muscarinic, responding to pilocarpine and acetylcholine. A component of the direct response was nicotinic, since it was activated by nicotine and blocked by hexamethonium in a dose-dependent manner. The axon-reflex response to nicotine and acetylcholine was partially blocked by pilocarpine, especially when application of pilocarpine preceded the procedure. The inhibition of the nicotinic response may be secondary to M1 antagonism since pilocarpine is an M2 agonist and M1 antagonist and pirenzepine, a specific M1 antagonist, caused similar effects as pilocarpine. PMID- 1638103 TI - Heart rate responses to deep breathing and 4-seconds of exercise before and after pharmacological blockade with atropine and propranolol. AB - Two autonomic tests which evaluate cardiac vagal activity, the respiratory sinus arrhythmia and the newer 4-second exercise test, have been compared. From electrocardiograph tracings, respiratory sinus arrhythmia was quantified by the ratio between the longest R-R interval during expiration and the shortest one during inspiration (E/I ratio), and the 4-second exercise test by the ratio between the last R-R interval before and the shortest one during exercise (B/C ratio). In 29 healthy subjects there was a correlation (R = 0.60, p less than 0.05) between the responses to the two tests. In a group of six healthy subjects the same tests were performed after autonomic blockade with intravenous atropine and/or propranolol. The heart rate rise during the 4-second exercise test was nearly abolished by atropine (mean +/- SD) (B/C: control = 1.53/0.33; after atropine = 1.04/0.03), whereas RSA was diminished to a lesser extent (E/I: control = 1.59/0.24; after atropine = 1.13/0.07). beta-adrenoceptor blockade did not affect the test ratios (after propranolol: B/C = 1.51/0.33 and E/I = 1.45/0.14). Successive tests during the following hour after atropine infusion showed a somewhat faster recovery of the respiratory sinus arrhythmia than the heart rate acceleration induced by the 4-second exercise test (p less than 0.05). We conclude that there may be some difference in the mechanisms which contribute to the heart rate changes in these two autonomic cardiovascular tests; these remain to be clarified. The 4-second exercise test may be an alternative to the respiratory sinus arrhythmia test in the non-invasive evaluation of cardiac parasympathetic activity. PMID- 1638104 TI - Autonomic involvement in inherited neuropathies. AB - The inherited peripheral neuropathies constitute a large group of disorders, in some of which the causative metabolic defect has been identified whereas in the majority it is still unknown. Amongst the former, autonomic involvement is an important component in porphyric neuropathy, in the familial amyloid polyneuropathies, in Fabry's disease and in dopamine beta-hydroxylase deficiency. The latter group includes the hereditary sensory and autonomic neuropathies in some of which, such as the Riley-Day syndrome, autonomic disturbances are prominent, whereas in others they constitute only a minor component of the symptomatology. Autonomic dysfunction is an important component of the neurological manifestations in multiple endocrine neoplasia type IIB. PMID- 1638105 TI - Spectral analysis of heart rate variability in bronchial asthma. AB - Sympathetic and parasympathetic activity was evaluated in ten healthy controls, nine asymptomatic, untreated asthmatic subjects and ten asthmatic patients during treatment for acute asthma, by measurement of the variation in resting heart rate using frequency spectrum analysis. Heart rate was recorded by ECG and respiratory rate by impedance plethysmography. Spectral density of the beat-to-beat heart rate was measured within the low frequency band 0.04 to 0.10 Hz (low frequency power) modulated by sympathetic and parasympathetic activity, and within a 0.12 Hz band width at the respiratory frequency mode (respiratory frequency power) modulated by parasympathetic activity. Acute asthmatics had higher heart rates than either of the other two groups; this was probably related to the effects of beta-adrenoceptor agonist medication. Sympathetically mediated heart rate variability (normalized low frequency power) was significantly lower in both asymptomatic (p less than 0.002) and acute (p less than 0.02) asthma subjects compared to controls. This is consistent with altered sympathetic/parasympathetic regulation of heart rate in subjects with bronchial asthma. PMID- 1638106 TI - Redistribution of blood flow in the cerebral cortex of normal subjects during head-up postural change. AB - Regional cerebral blood flow was measured in 21 normotensive subjects during supine rest and during head-up tilt to 70 degrees. The results showed significant and consistent regional cerebral blood flow changes in the frontal areas with lower relative flow distribution values (percentage of mean flow) during head-up tilt than during supine rest. The lower frontal flow distribution values during tilt were not related to habituation, to repeated measurements, or to the estimated level of arterial CO2 which was derived from expired end-tidal CO2 levels. None of the subjects had orthostatic hypotension and there was no significant difference in mean hemispheric blood flow between lying down and standing up. There was no significant gender difference in regional cerebral blood flow, although female subjects tended to have higher mean hemispheric flow than males in both postures. It remains to be established whether the flow decreases in the frontal cortex are caused by cerebral functional factors or by haemodynamic mechanisms. PMID- 1638107 TI - Cardiovascular instability during sleep and calm waking state in normal man. AB - Stroke volume, blood pressure, heart rate and blood flow in the calf and forearm were sampled every 20 min during the night sleep in eleven normal subjects. Stroke volume was measured by an impedance method with the use of a Minnesota cardiograph, and blood flow with venous occlusion plethysmography. The electroencephalogram was monitored routinely. Large variations in all sampled cardiovascular parameters were observed in all subjects. These variations were not interrelated nor were they correlated with any sleep stages. Variability in stroke volume ranged from 23% to 174%. Variability in vascular conductance in the calf was from 26% to 898%, in the forearm it was from 12% to 805%, in systolic blood pressure from 62% to 132%, diastolic blood pressure from 50% to 141% and in heart rate from 53% to 152%. In eight subjects sampling of cardiovascular parameters was carried out during the day, in a quiet but waking state. All sampled parameters varied, although during the day variations were smaller. It was therefore concluded that in normal man the cardiovascular system is in a state of perpetual oscillation during sleep or waking state until a specific pattern of adjustment is commanded by the central neurones. PMID- 1638108 TI - The autonomic nervous system and cardiac arrhythmias. AB - Disturbed autonomic nervous 'balance' of the sympathetic nervous and vagal outflows to the heart potentiates the experimental development of ventricular arrhythmias in laboratory animals. For some time the best evidence for the occurrence of a similar phenomenon in humans was provided by the long QT interval syndrome, sufferers of which are very prone to develop serious ventricular arrhythmias and in whom evidence exists of abnormal anatomy and function of the cardiac sympathetic nerves. Recently the case for disturbed autonomic function causing clinical arrhythmias has become more broadly based. Reduced baroreflex sensitivity after myocardial infarction, and low heart rate variability, both of which rest largely on vagal underactivity, have been shown to be associated with substantially increased risk of subsequent sudden death. A second observation is that patients having recovered from unexpected ventricular tachycardia or ventricular fibrillation have markedly increased cardiac sympathetic activity compared with appropriate reference groups, based on measurements of the rate of spillover of the sympathetic neurotransmitter, noradrenaline, from the heart to plasma. These clinical findings support a role for cardiac autonomic dysfunction, specifically sympathetic activation and vagal withdrawal, in arrhythmogenesis. These observations are timely, given the recent demonstration that most conventional anti-arrythmics are of little benefit in preventing sudden death. A reappraisal of the anti-arrhythmic activity of beta-adrenergic blocking drugs, and evaluation of potential benefits of other pharmacological and non pharmacological means of favourably altering cardiac autonomic function is now needed. PMID- 1638109 TI - Functional assessment of the sympathetic innervation of the microcirculation of the lower urinary tract: a preliminary report. AB - This paper presents preliminary data on a new method for testing the sympathetic innervation of the urothelium. A flexible laser Doppler probe was introduced into the urethra of two females and two male subjects. The percentage fall in laser Doppler flux following generalized sympathetic stimulation by taking an inspiratory gasp was measured. This resulted in 36%, 32%, 68% and 34% mean drop in urothelial blood flux. In the female subjects, the probe was advanced into the bladder and the procedure repeated, and the gasp resulted in 60% and 83% drop in flux. With laser Doppler fluxmetry, fall in microcirculatory blood flow associated with a generalized increase in sympathetic tone, therefore can be demonstrated. This method may be useful in the assessment of the integrity of the sympathetic innervation of the urothelium in patients with suspected autonomic dysfunction of the genitourinary tract. PMID- 1638110 TI - Influence of post-exercise activity on plasma catecholamines, blood pressure and heart rate in normal subjects. AB - The purpose of this study was to evaluate whether or not the type of activity performed during recovery might influence the magnitude of catecholamine outflow following exercise. Six active, male volunteers between 40-52 years recovered from strenuous treadmill exercise in three different ways; standing, supine rest and walking (2 mph, 0% grade). Measurements of noradrenaline (NA), adrenaline (A), heart rate and blood pressure were made at rest, peak exercise, and at 30 s intervals through 5-min of recovery. Peak exercise NA concentrations were approximately 1000% above those recorded as rest. Early recovery was marked by a continued increase in NA from peak exercise concentrations (4614 +/- 548 vs. 3264 +/- 485 pg/ml) which did not return to peak exercise levels until approximately 90 s of recovery. Adrenaline responses followed similar trends; however, the changes were not as sizable. Heart rate and diastolic blood pressure were significantly affected by the post-exercise condition; supine recovery produced significantly lower mean heart rates and mean diastolic blood pressures in comparison to standing or continued walking recovery conditions. Thus, these data indicate no specific recovery strategy will stem the rise in exercise-induced plasma catecholamines. Clinically, a strategy of continued walking, or better, supine recovery will best meet special clinical requirements, as well as limit the magnitude of the peak catecholamine increases. PMID- 1638112 TI - Gene expression and differentiation. PMID- 1638111 TI - Ambulatory blood pressure in patients with Parkinson's disease without and with orthostatic hypotension. AB - Non-invasive ambulatory recordings of blood pressure and heart rate were performed using a Spacelabs device during day and night periods in patients with Parkinson's disease with (n = 19) or without orthostatic hypotension (n = 19). In patients with orthostatic hypotension, the average systolic and diastolic blood pressure during the night (137 +/- 5/80 +/- 3 mmHg) was higher (p less than 0.05) than during the day period (121 +/- 3/76 +/- 2 mmHg). In patients without orthostatic hypotension, a decrease in blood pressure was recorded during the nocturnal period. In patients with orthostatic hypotension, the blood pressure variability was higher (p less than 0.05) during the day (systolic: 14.6 +/- 1.3%; diastolic: 16.5 +/- 1.0%) than during the night (systolic: 9.1 +/- 0.8%; diastolic: 10.8 +/- 1.1%). The blood pressure load (percentage of values above 140/90 mmHg) during the night was significantly higher than during the day for both systolic (41.2 +/- 8.1 vs. 19.6 +/- 4.7%) and diastolic blood pressure (24.9 +/- 6.9 vs. 16.3 +/- 4.9%). There was a decrease in heart rate in both groups during the night. A fall of 25 mmHg or more in systolic blood pressure after meals occurred in ten patients with orthostatic hypotension and in one patient without orthostatic hypotension. These results indicate that orthostatic hypotension in Parkinson's disease is associated with specific modifications of ambulatory blood pressure including loss of circadian rhythm of blood pressure, increased diurnal blood pressure variability and post-prandial hypotension. PMID- 1638113 TI - Gene expression and differentiation. PMID- 1638114 TI - Structure of the leucine zipper. AB - In the basic-region leucine-zipper domain, flexible DNA-binding arms are juxtaposed by a two-stranded, parallel coiled-coil motif called the leucine zipper. Genetic, physical and structural studies of the leucine zipper identify interactions that help determine the stability and specificity of dimerization and DNA binding. PMID- 1638115 TI - The SRF and MCM1 transcription factors. AB - The mammalian transcription factor SRF (serum-response factor) and the related Saccharomyces cerevisiae transcription factor MCM1 are the prototypes of a new class of dimeric DNA-binding proteins. Their function is regulated in part by the interactions of their DNA-binding domains with accessory proteins. Recent work has advanced the functional characterization of the contributions of SRF and MCM1, and their accessory proteins to transcriptional activation. PMID- 1638116 TI - Myc and Max function as a nucleoprotein complex. AB - The Myc family of oncoproteins are thought to regulate proliferation and differentiation in a wide variety of cell types. Recent studies show that Myc proteins form sequence-specific DNA-binding complexes with Max, a new member of the helix-loop-helix leucine zipper protein class. The properties of the Myc-Max complex suggest a mechanism for Myc's function in both normal and neoplastic cell behavior. PMID- 1638117 TI - Eukaryotic coactivators associated with the TATA box binding protein. AB - Recent studies of regulated RNA polymerase II transcription have uncovered a new class of molecules called coactivators. These are tightly associated with the TATA box binding protein and are required in addition to promoter-specific activators and the basal transcription factors in order to achieve stimulated levels of transcription. PMID- 1638118 TI - Muscle basic helix-loop-helix proteins and the regulation of myogenesis. AB - Significant progress has been made in defining the structural motifs that distinguish the muscle-specific from other basic helix-loop-helix proteins. Evidence is accumulating for multiple levels of regulation of the expression and action of the muscle basic helix-loop-helix factors. PMID- 1638120 TI - Mechanisms of liver-specific gene expression. AB - Significant advances in the field of hepatocyte-specific gene expression have been made during the past year. Several new transcription factors have been cloned and partially characterized. Analyses of the promoter regions of several factors have also been initiated and Drosophila homologs for two of these factors have been found, opening the way for studies on development. PMID- 1638119 TI - Myb: a transcriptional activator linking proliferation and differentiation in hematopoietic cells. AB - Myb is a transcriptional activator protein with repeated helix-turn-helix DNA binding motifs distantly related to the homeodomain. In hematopoiesis, c-myb appears to control both cell proliferation and differentiation. The mechanisms by which the leukemogenic potential of c-Myb is activated are complex and involve truncations, point mutations, and fusion or coexpression with other proteins. PMID- 1638121 TI - Expression of spatially regulated genes in the sea urchin embryo. AB - Spatially controlled genes expressed in the early sea urchin embryo have been characterized, and the patterns of expression in terms of the mechanisms by which this embryo accomplishes its initial set of founder cell specifications are the subject of current discussion. Sea urchin transcription factors that have been cloned are classified with respect to their target sites and the genes they regulate. Among the best known of the sea urchin cis-regulatory systems is that controlling expression of the Cyllla gene, which encodes an aboral ectoderm specific cytoskeletal actin. The Cyllla regulatory domain includes approximately 20 sites of DNA-protein interaction, serviced by about ten different factors. Certain of these factors are known to negatively control spatial expression, while others positively regulate temporal activation and the level of Cyllla gene expression. Differential, lineage-specific gene expression is instituted in the sea urchin embryo by mid-late cleavage, prior to any cell migration or overt differentiation, and shortly following lineage segregation. PMID- 1638122 TI - The Drosophila nuclear receptors: new insight into the actions of nuclear receptors in development. AB - In Drosophila melanogaster, an increasing number of members of the steroid hormone receptor superfamily are being identified and characterized. Molecular and genetic analysis of receptor function provides evidence for a set of functions underlying the determination of pattern formation, metamorphosis, eye development, and reproduction. Many of the Drosophila receptor genes show striking homologies to mammalian receptor genes. This suggests that genetic analysis in flies could facilitate the generation of biological models that pertain to complex hormonal responses in development and which are relevant to both vertebrate and invertebrate systems. PMID- 1638123 TI - Silencing: the establishment and inheritance of stable, repressed transcription states. AB - Silencing refers to a particular type of transcriptional repression characterized by the formation of a genetically heritable, repressed transcriptional state. Examples of silencing include position-effect variegation, X-chromosome inactivation, and the repression of the silent mating-type gene loci in yeast. Recent discoveries suggest that silencing in yeast, like silencing in larger eukaryotes, results from a particular chromatin structure that defines a chromosomal domain. In addition, a chromosomal origin of DNA replication is required for silencing in yeast, suggesting that DNA replication plays a role in forming functional chromosomal domains. PMID- 1638124 TI - Activation of HIV transcription by Tat. AB - Recent studies suggest that the human immunodeficiency virus transactivator, Tat, increases expression of viral genes primarily by enhancing the efficiency of transcriptional elongation. The degree to which Tat influences elongation may depend on the rate of transcriptional initiation. Current models in which Tat interacts with the transcription complex suggest directions for future studies. PMID- 1638125 TI - Sex differentiation: the role of alternative splicing. AB - Sex differentiation in Drosophila is controlled by a regulatory cascade with at least three regulated alternative RNA-processing events. The results of recent work have verified much of the earlier molecular and genetic work in this field and have provided a demonstration that both positive and negative regulatory mechanisms are involved. PMID- 1638126 TI - Gene expression and differentiation. PMID- 1638127 TI - Development. PMID- 1638128 TI - Control of photoreceptor development. AB - Recent studies of cell type determination in the vertebrate retina suggest that rod photoreceptor development involves interactions among cells that are mediated, at least in part, by temporally regulated diffusible signals. In this review the strategies used to generate rods in the vertebrate retina are compared with those described for photoreceptor development in the Drosophila retina. PMID- 1638129 TI - The control of neuronal identity in the developing cerebral cortex. AB - Recent studies of the lineages and developmental potential of cortical neurons show that cell fates are progressively restricted during cerebral cortical development. Cell lineage experiments suggest that individual cortical precursors are multipotent, as their progeny can end up in different cortical areas, and in different layers within an area. Transplantation studies have shown that young neurons are committed very early on to adopting a given laminar position, in a manner correlated with their birth date in the ventricular zone. Neurons in different neocortical areas, however, retain a functional and anatomical equipotentiality well into cortical development, suggesting that positional cues determine a cell's area-specific identity. PMID- 1638130 TI - Motor axon pathfinding. AB - Recent studies have provided a significant advance in our understanding of motor axon pathfinding. In particular, sources of guidance cues and some of the mechanisms used by motor growth cones during pathfinding have been identified. PMID- 1638131 TI - Mesodermal control of neural cell identity in vertebrates. AB - It has long been appreciated that the differentiation and patterning of neural cells is controlled in part by inductive signals from the mesoderm. Several recent experiments have revealed that distinct mesodermal signals act throughout early neural development and have begun to address the nature and sources of such signals. PMID- 1638132 TI - Growth cone guidance in the zebrafish central nervous system. AB - The accessibility and simplicity of the zebrafish embryo have allowed researchers to make a detailed characterization of pathfinding by identifiable growth cones. The growth cones follow precise cell-specific pathways to their targets. Analyses of pathfinding in mutant and experimentally manipulated wild type embryos have shown that growth cones accomplish this by interacting with specific cellular cues in their environment, many of which are likely to be redundant. PMID- 1638133 TI - Guidance of neuroblast migrations and axonal projections in Caenorhabditis elegans. AB - The nematode Caenorhabditis elegans provides an excellent model system in which to study the mechanisms involved in the development of the nervous system. Mutation analyses have now identified several genes that appear to be important in the interaction of neuroblasts and axons with both guidance cues and their target cells. PMID- 1638134 TI - Pathway recognition by neuronal growth cones: genetic analysis of neural cell adhesion molecules in Drosophila. AB - Genetic analysis has finally come of age in the study of neural cell adhesion molecules and their function during growth cone guidance in Drosophila. Recent studies have shown that fasciclin II, a neural cell adhesion molecule of the immunoglobulin superfamily, functions as a recognition molecule for the MP1 axon pathway, thus serving as the first molecular confirmation for the existence of functional labels on specific axon pathways in the developing organism. PMID- 1638135 TI - Guidepost cells. AB - Guidepost cells, as classically defined in the grasshopper embryo have only rarely been found in other systems. If the concept of guidepost cells is expanded, recognizing that any special role of specific cells in axon guidance is a function of the entire landscape in which axons are growing, and that growth cone--guidepost interactions may share mechanisms with many other cell--cell interactions, then numerous examples are found in both the peripheral and central nervous systems of many species. PMID- 1638136 TI - Repellent cues in axon guidance. AB - There is increasing evidence that axons are guided by repulsion in several regions of the developing nervous system, although this has yet to be confirmed directly in vivo. As more candidate repulsion molecules are identified, it is becoming clear that collapse of the growth cone in vitro may be mediated by more than one intracellular mechanism. The present emphasis on molecular cloning of the ligands and their receptors should enable a proper definition of their function during development. PMID- 1638137 TI - Axon guidance by molecular gradients. AB - In the past year, evidence indicating that some developing axons are guided to their targets, at least in part, by gradients of diffusible chemoattractants secreted by their target cells has continued to accumulate. It has also been shown for the first time that axons can orient in response to smooth gradients of immobilized substrate molecules. PMID- 1638138 TI - Development of connectional diversity and specificity in the mammalian brain by the pruning of collateral projections. PMID- 1638139 TI - How are specific connections formed between thalamus and cortex? AB - During development precise thalamocortical connections are established, with reciprocal connections forming correctly in a laminar pattern as well as between the correct thalamic and cortical areas. Recent evidence suggests that both spatial and temporal cues may account for this specificity. PMID- 1638140 TI - Patterning of retinotectal connections in the vertebrate visual system. AB - Recent work on the retinotectal projection clearly establishes the roles of neuronal activity and position-based cues in the patterning of nerve connections. In some species, the high degree of spatial order has been shown to emerge from a continued process of terminal growth and refinement. The future challenge is now to determine how multiple cues work together to guide the sculpting of the final pattern. PMID- 1638142 TI - Development. PMID- 1638141 TI - Acquisition of regional and cellular identities in the developing zebrafish nervous system. AB - In the past year, several new techniques have been used with great success in the study of nervous system development in the zebrafish. Perhaps the most exciting results have come from experiments in which single identified cells or small groups of cells have been transplanted between embryos in order to examine cell determination and the site of action of genetic mutations. PMID- 1638143 TI - Cognitive neuroscience. PMID- 1638144 TI - The status of cognitive neuroscience. AB - Cognitive neuroscience rests on findings, methods, and theory from three fields: experimental psychology, systems-level neuroscience, and computer science. The strong trend over the past few years has been for a greater integration across these fields. The influence of this interdisciplinary approach on current research on memory, perception, and language will be illustrated. PMID- 1638145 TI - Visual cortex: cartography, connectivity, and concurrent processing. AB - The mammalian visual cortex contains a complex mosaic of areas that are richly connected with one another. Recent progress has advanced our understanding of both macroscopic and microscopic aspects of cortical organization, and of information flow within and between functionally specialized processing streams. PMID- 1638146 TI - Face recognition. AB - The study of face-selective neurons in the monkey temporal lobe, and face recognition deficits in humans after brain damage have both become very active fields of investigation. Face-selective neurons appear to be members of ensembles for coding faces rather than individual face detectors or grandmother cells. They reflect the more general role of temporal cortex in pattern recognition. In humans there are a variety of face-processing impairments that result from damage to different areas, and which reflect interference at different levels of processing of the facial image. PMID- 1638147 TI - Agnosia. AB - Object recognition can break down in a variety of ways after brain damage. The resulting different forms of agnosia provide us with useful constraints on theories of normal object recognition. Recent studies suggest a division of labor for the recognition of different types of stimuli (common objects, words, faces, direction of eye gaze, spatial relations among parts of the human body), a high degree of interactivity in the processes underlying object recognition, and the possibility that recognition and awareness of recognition may be neurally distinct. PMID- 1638149 TI - Organization of space perception: neural representation of three-dimensional space in the posterior parietal cortex. AB - The representation of perceptual space in the posterior parietal cortex can be divided into at least two categories: far space, beyond arm's reach, and peripersonal space, within arm's reach. These are encoded by different groups of neurons that are closely related to the control of gaze and the guidance of arm and hand movement, respectively. PMID- 1638148 TI - The neurobiology of selective attention. AB - Research in the field of selective visual attention has recently seen substantial progress in several areas. Neuroimaging and electrical recording results have indicated that selective attention amplifies neural activity in prestriate areas concerned with basic visual processing. Imaging and cellular studies are delineating the networks of anatomical areas that serve as the source of attentional modulation and have suggested that these networks are anatomically distinct from the sites of the resulting amplifications. Cognitive studies of visual search have explored the role of these amplified computations in the integration of visual features into objects. Attentional effects in normal subjects, and their disruption following brain injury, have revealed the mental representations upon which attention operates. PMID- 1638150 TI - The perception of visual motion. AB - Recent developments have led to a greater insight into the complex processes of perception of visual motion. A better understanding of the neuronal circuitry involved and advances in electrophysiological techniques have allowed researchers to alter the perception of an animal with a stimulating electrode. In addition, studies have further elucidated the processes by which signals are combined and compared, allowing a greater understanding of the effects of selective brain damage. PMID- 1638151 TI - Language development. AB - Recent research suggests that our ability to learn language is innate, but not necessarily domain-specific. That is, language development appears to be based on a relatively plastic mix of neural systems that also serve other cognitive and perceptual functions. Evidence in support of this conclusion includes neural network simulations of language learning, event-related brain potential studies of normal language development, and studies of language development in several clinical populations of subjects suffering focal brain injury, specific language impairment, and contrasting forms of mental retardation. PMID- 1638152 TI - Knowledge systems. AB - The primate brain appears to store knowledge in widely distributed neural systems. Recent evidence suggests that these systems are specialized with respect to their capacity for supporting acquisition and retrieval of different domains and levels of knowledge. PMID- 1638153 TI - Brain mechanisms of emotion and emotional learning. AB - The amygdala appears to play an essential role in many aspects of emotional information processing and behavior. Studies over the past year have begun to clarify the anatomical organization of the amygdala and the contribution of its individual subregions to emotional functions, especially emotional learning and memory. Researchers can now point to plausible circuits involved in the transmission of sensory inputs into the amygdala, between amygdaloid subregions, and to efferent targets in cortical and subcortical regions, for specific emotional learning and memory processes. PMID- 1638154 TI - Oculomotor control and spatial processing. AB - In the past year research in the oculomotor system has concentrated on some hitherto neglected areas, and also caused a re-evaluation of several long standing concepts. Careful studies of the translational (otolith) vestibulo ocular reflex and the torsional system have demonstrated their importance. A re evaluation of the role of the superior colliculus in the generation of saccades has provided evidence for its participation in the feedback process. New studies of the interaction of eye movements and visual processing have shown that the brain can compensate for the visual effects of eye movements and maintain a retinotopic representation of visual space for the saccadic system. PMID- 1638155 TI - Memory. AB - The key interrelated issues in the neurobiology of memory are to identify the neural circuitries essential for memory formation, localize sites of memory storage and analyze mechanisms of memory formation, storage and retrieval. Several circuits have now been identified in vertebrates and researchers are investigating their properties, in particular the role of glutamate receptors and long-term potentiation, in memory formation. Invertebrate preparations continue to be of value and recent studies suggest that changes in gene expression and protein synthesis may be important in long-term sensitization. PMID- 1638156 TI - Computational approaches to hippocampal function. AB - The results of theoretical work have led researchers to suggest that the hippocampal formation may maximize its memory storage capacity by recoding events into patterns that are as dissimilar to one another, and which use as few neurons per event, as possible. PMID- 1638157 TI - Is the cerebellum involved in learning and cognition? AB - Current studies are examining whether the cerebellum has a functional role in non motor tasks using both behavioral and physiological methods with animals, and computer simulations of a classical conditioning task. Cerebellar involvement in cognition has been assessed in studies with healthy and neurologically impaired humans. The results have led to new hypotheses that are providing testable predictions about the role of the cerebellum in perception, attention, and other cognitive functions. PMID- 1638158 TI - Neuroimaging. AB - Recent advances in neuroimaging have led to an increase in the types of studies possible in the field of cognitive neuroscience. Researchers are now using neuroimaging to enhance classic approaches, such as lesion-behavior studies, as well as provide information about normal functions at levels that were previously difficult to assess. PMID- 1638159 TI - Cognitive neuroscience. PMID- 1638160 TI - Kearns-Sayre syndrome: a case report and review. AB - In 1958, Kearns and Sayre described a multisystem entity, now known as Kearns Sayre syndrome (KSS). The syndrome is defined as exhibiting a triad of thus far unexplained degenerative conditions: progressive external ophthalmoplegia, retinal pigmentary degeneration, and heart block. Commonly accompanying findings include cerebellar dysfunction and CSF protein levels above 100 mg/dl. Symptoms usually appear in early childhood, but the onset has been seen occasionally in young adults. KSS is a mitochondrial disorder that occurs rarely; the actual incidence is unknown. Ocular findings consist of bilateral ptosis, chronic progressive external ophthalmoplegia, and pigmentary retinopathy. Corneal clouding and optic neuritis are infrequent. We herein report a classic case of Kearns Sayre syndrome and discuss the findings. PMID- 1638161 TI - A study of the effects of angiotensins 1, 2, 3 and bradykinin on the replication of bovine retinal capillary endothelial cells and pericytes. AB - The renin-angiotensin system of the human eye may play a role in the regulation of retinal blood flow and the development of new vessels. We have investigated whether angiotensins 1, 2 and 3 or bradykinin, in concentrations ranging between 1 x 10(-12) and 1 x 10(-6), have any mitogenic activity on cultured bovine retinal endothelial cells (BREC) and pericytes (BRP). Cell replication was assessed by 3H-thymidine incorporation and, in the case of BREC and AT-2, also by cell counts. AT-2 was also tested on bovine aortic EC (BAEC). None of the substances elicited any response on BREC, BRP or BAEC. Whether angiotensin(s) induce angiogenesis in retinal vessels in vivo remains to be established but this does not appear to occur through direct stimulation of cell replication. PMID- 1638162 TI - Treatment of calcific band keratopathy by Nd:YAG laser. AB - A new technique is presented for the treatment of secondary calcific band keratopathy. The Nd:YAG laser was used for the disruption and removal of corneal calcium deposits. This technique was used in seven cases with satisfying results. PMID- 1638164 TI - Prevalence of myopia in open angle glaucoma. AB - In this study concerning the prevalence of myopia in patients with open angle glaucoma, its distribution was analyzed within the sample tested in relation to the refraction defect size, compared with a control group of non-glaucomatous myopic subjects. The overall myopic rate was 17.2% of the glaucomatous patients; high myopia was more frequent in the subjects with open angle glaucoma (p less than 0.001) than in the myopic patients, thus appearing as a possible risk factor for the development of glaucoma. PMID- 1638163 TI - Hypertensive gas technique for enucleation of choroidal melanomas: a preliminary report. AB - The hypertensive gas technique induces avascularity within the eye during enucleation of a melanoma. Before touching the eye for enucleation, pressure is raised to maximum by an intravitreal injection of approximately 1.4 ml of gas (perfluorocarbon, air) resulting in a rock-hard eye. Avascularity persists for the duration of enucleation. From 9/1987 to 6/1989, 15 patients with choroidal melanomas were enrolled in a prospective study with the hypertensive gas technique instead of prior radiotherapy (the death rate in that series was five out of 26 melanoma patients at three years). Inclusion criteria for the hypertensive gas technique study were the same as for our previous irradiation series: (1) absence of detectable metastases and (2) a choroidal melanoma too large for a radioactive plaque. The average base diameter of melanomas measured 13.2 mm, height 8.4 mm. The cytology was: 11x spindle, 3x mixed, 1x epithelioid cells. At re-examination in 7/1991 (average follow-up 33 months) two diabetics had died with no detectable metastases prior to death, and one of the 15 melanoma patients had died with metastases 24 months after enucleation. So far the hypertensive gas technique for enucleation of a melanoma eye seems to have no adverse effect on survival. It seems to be a simple alternative to the precautions taken otherwise and it facilitates enucleation with practically no bleeding from the globe. PMID- 1638165 TI - Repeated melting of corneal grafts in a patient with rheumatoid arthritis and Sjogren's syndrome. AB - We present a case of corneal melting in a patient with severe rheumatoid arthritis and Sjogren's syndrome. The melting appeared in the area of a bacterial corneal ulcer that healed after treatment with antibiotics. No signs of scleritis were present. Repeated melting of two corneal grafts was seen after surgery. PMID- 1638166 TI - Dark choroid in cone-rod dystrophy. AB - An unusual pattern of dark choroid in an eight-year-old girl is described. The ophthalmoscopic, fluorescein angiographic and functional changes were indicative of progressive cone-rod dystrophy. PMID- 1638167 TI - Rickettsial keratitis in a case of Mediterranean spotted fever. AB - The first documented case of infectious keratitis (an ameboid-like corneal ulcer) caused by Rickettsia conorii is described. Corneal infection was probably caused by contamination through the tears during systemic rickettsial dissemination. Topical tetracyclin ointment was effective. Rickettsial keratitis should be considered in the differential diagnosis of ameboid-like corneal ulcers in areas where Mediterranean spotted fever is endemic. PMID- 1638168 TI - Improvement of siderotic ERG. AB - For fear of endophthalmitis and siderosis, ferrous intraocular foreign bodies are usually removed as soon as they are discovered; markedly reduced, siderotic ERG changes are considered permanent. We report a patient who presented with a chronically retained intravitreal foreign body and significant clinical as well as electrophysiologic signs of siderosis. Only 3 months after surgery, the ERG showed almost complete recovery. If siderosis is not present, adequate and regular follow-up examinations may in certain cases substitute for immediate removal of chronically retained intraocular foreign bodies. PMID- 1638169 TI - Panic disorder: a biological perspective. AB - Panic disorder (PD) was first delineated as a separate diagnostic entity 25 years ago. It is a prevalent disorder that responds well to pharmacological interventions, most notably to antidepressants and benzodiazepines. PD and other psychiatric disorders, such as generalized anxiety disorder and major depression, overlap clinically, but it is unresolved whether they also overlap biologically. Finally, the pathogenesis of PD is still unclear. Theories linking panic to increased sensitivity to CO2 or serotonin are preliminary, while alpha 2 adrenergic dysregulation in panic is still unproven. However, the development of new, selective, receptor agonists and antagonists in combination with imaging techniques may produce some of the answers to the questions raised since. PMID- 1638170 TI - Psychopharmacological treatment of social phobia: clinical and biochemical effects of brofaromine, a selective MAO-A inhibitor. AB - There is circumstantial evidence that antidepressants, particularly monoamine oxidase inhibitors (MAOIs) and beta-blockers, may have some beneficial effects in social phobia. In this study 30 patients with social phobia (DSM-IIIR) were treated with the selective and reversible MAO-A inhibitor brofaromine, using a 12 week double-blind placebo controlled design. A clinical relevant improvement was seen in 80% of the patients treated with brofaromine (150 mg daily). A significant improvement was found on measures of social anxiety, phobic avoidance, general (or anticipatory) anxiety and interpersonal sensitivity in patients on brofaromine, but not on placebo. Biochemical measurements revealed a decrease in turnover of noradrenaline, serotonin and dopamine as assessed by the plasma metabolite levels, and an increase in nocturnal release of melatonin. Most prominent side-effect was middle sleep disturbance. No changes in blood pressure were observed. During a follow-up period of 12 weeks a further improvement was found in patients treated with brofaromine. PMID- 1638171 TI - CBF and cognitive evaluation of Alzheimer type patients before and after IMAO-B treatment: a pilot study. AB - Ten patients diagnosed as affected by primary degenerative dementia of the Alzheimer type, with a mild to moderate cognitive and behavioral impairment, were studied in a double blind design when taking for 60 days 5 mg twice a day of L deprenyl or placebo. Cognitive functions and cerebral blood flow were assessed at the beginning and at the end of treatment by a wide array of memory, attention, and language efficiency measures and by SPECT-99TcHMPAO procedure. Reduced CBF on the parietal lobes was demonstrated in the patients at baseline together with a reduction of memory and cognitive efficiency. At the end of the treatment patients who received L-deprenyl showed an improvement in cognitive efficiency and no changes in CBF, while patients treated with placebo showed a worsening of cognitive efficiency and further reduction of parietal lobe CBF. PMID- 1638172 TI - Effects of MK-801 and antidepressant drugs in the forced swimming test in rats. AB - The effects of MK-801, a non-competitive NMDA receptor antagonist, and of antidepressant drugs were studied in the forced swimming test in rats. MK-801 reduced immobility time. Combined treatment with MK-801 + imipramine induced a stronger effect in Porsolt's test than administration of either drug alone. Citalopram was inactive when given alone but it potentiated the antidepressant like effect of MK-801. Haloperidol and prazosin antagonized the effect induced by MK-801 + IMI or CIT. Mianserin interacted with MK-801 in a similar way but to a lesser extent. Its effect was antagonized by haloperidol but not by prazosin. The reduction of the immobility time was also observed in those experimental paradigms in which the locomotor activity was not increased. The results indicate that synergism may exist between antidepressants and MK-801. PMID- 1638173 TI - Antidepressant treatment prevents chronic unpredictable mild stress-induced anhedonia as assessed by ventral tegmentum self-stimulation behavior in rats. AB - The effect of chronic unpredictable mild stress on sensitivity to reward was evaluated using the brain self-stimulation procedure. Rats were allowed to electrically self-stimulate the ventral tegmental area, one of the main cerebral structures subserving positive reinforcement. Stimulation thresholds (frequency of stimuli) for self-stimulation responses were determined prior to, during, and following a 19-day period of exposure to a variety of mild unpredictable stressors. Stimulation threshold was increased in stressed rats, suggesting a decrease in the rewarding properties of brain stimulation. This deficit became evident after about 1 week of mild stress, lasted throughout the stress period, and progressively diminished following termination of the stress regime. In stressed rats concomitantly treated with the tricyclic antidepressant desipramine (5 mg/kg b.i.d.), no stress-induced increase in self-stimulation threshold was observed. However, desipramine did not modify self-stimulation threshold in non stressed animals. Thus, the increased threshold for brain self-stimulation produced by a period of chronic unpredictable mild stress can be completely prevented by concomitant antidepressant treatment and may provide an heuristic animal model of depression. PMID- 1638174 TI - Relationship of symptomatology of schizophrenia and tardive dyskinesia. AB - The role of drug factors and patient factors in the development of tardive dyskinesia (TD) was examined in 31 TD patients and 31 non-TD patients matched by age and sex. TD patients achieved significantly lower total scores on the anxiety depression factor of Brief Psychiatric Rating Scale (BPRS) (5.2 +/- 1.4 vs. 6.5 +/- 2.2; less than P) and significantly higher total scores on the activation factor (6.4 +/- 2.2 vs. 5.3 +/- 2.5; less than P). The finding that TD patients were less depressed may be explained by a hypermonoaminergic state developing in TD. Based on the findings of this study it is suggested that catatonic schizophrenic patients are more vulnerable to the development of TD. PMID- 1638175 TI - Alterations in brain cholecystokinin receptors in suicide victims. AB - Cholecystokinin (CCK) and benzodiazepine receptor binding characteristics were analyzed in the brain tissue samples from 19 suicide victims and 23 control cases. In the frontal cortex, significantly higher apparent number of CCK receptors and affinity constants were found in the series of suicide victims. These differences between suicides and controls were present in similar proportions when the suicide cases with depressive syndrome or violent or non violent means of self-killing were compared to matched controls. However, when the samples were split into subgroups consisting of persons either below or over the age of 60 years, significant differences in the CCK receptor characteristics in the frontal cortex were observed only between younger suicides and controls. Furthermore, the younger suicide victims had a higher density of CCK receptors in the cingulate cortex, whereas in older suicides the value was lower as compared to age-matched controls. No difference in benzodiazepine receptor binding was found between control and suicide groups. The results of this investigation suggest that CCK-ergic neurotransmission is linked to self-destructive behaviour, probably through its impact on anxiety and adaptational deficits. PMID- 1638176 TI - Low doses of morphine reduce voluntary alcohol consumption in rhesus monkeys. AB - Experimental opioid modulation has been found to influence the consumption of alcohol in animals. Whereas it has generally been agreed upon that opiate antagonists reduce alcohol consumption, the results with opiate agonists are less consistent. The present study reports on the effect of low doses of morphine in 8 adult male rhesus monkeys that had a free choice in drinking water, a 16% and a 32% ethanol/water solution, (a) during continuous ad libitum access (Experiment I), and (b) after 2 days of alcohol abstinence (Experiment II). In both experiments each monkey received a single morphine injection (i.m.) in 5 different doses (0.03, 0.06, 0.17, 0.50, 1.50 mg.kg-1); each morphine injection (i.m.) was placebo-controlled in a cross-over design. Consumption was measured from 16.00 h in the afternoon (30 min after injection) to 08.30 h the next morning. In Experiment I after 0.50 and 1.50 mg.kg-1 of morphine ethanol intake and water consumption were both reduced during the first hours after injection; only ethanol intake remained reduced during the subsequent night. Effects lasted not longer than 24 h. In Experiment II, morphine administered 30 min before reintroduction of ethanol solutions reduced ethanol intake at doses of 0.17, 0.50 and 1.50 mg.kg-1; water consumption was unaffected. The reduction lasted for the subsequent night after the 2 highest doses. Records obtained of various spontaneous behavioural activities made it unlikely that the used dose range had induced some aspecific sedation; monkeys remained alert and active. The results are contradictory with studies in which low doses of morphine stimulated alcohol drinking in rats. The present results seem to support the hypothesis that at least in monkeys morphine can compensate for some effects of alcohol. PMID- 1638177 TI - Galactorrhea in the neuroleptic malignant syndrome. AB - A case of schizophrenia with neuroleptic malignant syndrome (NMS) presented difficulties in differential diagnosis. However, the presence of severe galactorrhea contributed decisively to relate the clinical picture with the administration of neuroleptics. We propose that presence of galactorrhea or disorders in prolactin (PRL) secretion should be investigated in NMS. PMID- 1638178 TI - Arsenic in induced hair of the rat and its relation to the content in various organs during chronic exposure. AB - The behaviour of the rate of transfer of arsenic to hair induced at various times during a long-term exposure experiment was examined in rats supplied with 3 mg arsenic per litre of drinking water in the form of chloride. The arsenic was supplied during a period of 560 days. At the beginning a sharp increase was seen in the rate of transfer of arsenic to induced hair, as well as in the content of arsenic in the various organs. Subsequently, the rate of transfer to hair increased slowly but steadily up to the end of the experiment. During that time the level of arsenic in the liver and in the kidneys remained constant, whereas that in the brain and in some other organs increased slowly and irregularly. The correlation between the arsenic in the induced hair and that in the organs was statistically significant in all comparisons. Correlation coefficients greater than 0.7 were found in the comparisons of the content in the induced hair with those in the heart, the pancreas and the forebrain. The findings suggest that the rate of transfer of endogenous arsenic depends on two factors, one being the level of body intake of arsenic during the period of hair growth, the other the degree to which the element had accumulated in the body during the time which elapsed between the onset of arsenic supply and the start of hair growth. PMID- 1638179 TI - Taste alterations in liver cirrhosis: are they related to zinc deficiency? AB - Patients with chronic liver disease may have taste impairment and altered zinc metabolism. We evaluated Taste Detection Thresholds (TDTs) in 60 patients with liver cirrhosis and correlated the findings with disease severity and alcoholic etiology. Plasma zinc levels and urinary output were also measured. A placebo controlled treatment trial with zinc sulphate was made in 15 patients with compensated cirrhosis in order to ascertain whether zinc deficiency caused taste alterations. Taste detection of salty, sweet and acid tastants was significantly impaired in all cirrhotic patients in comparison with normal subjects. TDTs were not influenced either by the etiology or the severity of the disease. All groups of patients had low plasma zinc levels and decompensated cirrhosis had a significantly increased urinary output of zinc. No correlation was found between taste acuity and plasma zinc levels when only cirrhotic patients were considered. The effect of zinc supplementation on TDTs did not appear to be inferior to that of the placebo. Our results indicate that taste impairment in cirrhotics is due to the disease process per se and not to zinc deficiency. PMID- 1638180 TI - Sex-related effects of zinc deficiency on the selenium metabolism in rats. AB - The effects of a low zinc status on selenium metabolism were investigated in female and male rats which were fed diets with low and adequate zinc contents and a suboptimal selenium content. For the selenium content and glutathione peroxidase activity in the liver and plasma of the female animals no differences were found between the low zinc group and the pair-fed zinc-adequate control group. In the male rats zinc depletion resulted in testis atrophy and decreased testicular contents of selenium and glutathione peroxidase. In the pair-fed and ad libitum-fed control groups the levels of hepatic selenium and glutathione peroxidase and plasma glutathione peroxidase in the males were lower than those in the females. In the low zinc group, however, they rose to the levels of the females. The results indicate that these effects of zinc deficiency on selenium metabolism are sex-specific and suggest that they are related to changes in the sex hormone status of the male animals. PMID- 1638181 TI - Trace elements in full-term neonate hair. AB - Proton Induced X-ray Emission (PIXE) was employed to measure simultaneously the concentration of 12 trace elements in the hair of 141 AGA newborn infants at term. Log-normal distributions were measured for all elements. There were no significant differences in trace elements in relation to sex, gestational age and body weight. The geometric means (mg/kg) were: Cr, 1.5 +/- 0.2; Mn, 1.5 +/- 0.1; Fe, 51 +/- 4; Ni, 1.0 +/- 0.2; Cu, 6.1 +/- 0.3; Zn, 133 +/- 3; As, 0.055 +/- 0.005; Se 0.81 +/- 0.05; Br, 1.3 +/- 0.1; Pb, 1.4 +/- 0.2; Rb, 0.22 +/- 0.03; and Sr, 1.5 +/- 0.2. Some direct and inverse partial correlations among elements were found at different levels of significance. Each element was significantly correlated with at least one other. Zinc and copper concentrations were lower compared to data in the literature. The high values of chromium and selenium concentrations were in agreement with previous findings. The manganese level was in accordance with previous data. The Zn/Cu ratio agreed very well with the data in the literature. This indicates that while concentration values may be subjected to large variations due to living conditions, correlations could be more stable and therefore offer insight on the regulatory mechanisms governing trace element metabolism in man. PMID- 1638182 TI - Excretion and distribution of injected radiozinc in rats as influenced by the type of carbohydrate. AB - The aim of this study was to investigate the effect of different dietary sugars on Zn status by measuring the excretion and body distribution of intramuscularly injected zinc-65 in growing rats. Thirty-two weanling rats (39.4 +/- 2.7 g) were allotted to six diets in which starch (56%) was partially substituted for glucose (15%), fructose (15%), sucrose (30%), galactose (15%) or lactose (30%). Diets uniformly supplied 22 mg/kg (dry matter) of Zn. Three days after the start of the dietary regimen each rat was injected with 40 micrograms Zn, labelled with 380 kBq 65Zn, in saline solution. Feces and urine were collected for 15 days; thereafter 65Zn distribution in the liver, pancreas, kidneys, gastrointestinal tract and residual carcass was assessed. Fecal 65Zn excretion was not significantly influenced by the diets, although the gastrointestinal tract of the galactose- and lactose-fed animals contained more 65Zn than did those fed the other diets. 65Zn in the urine and kidneys of the galactose-fed rats was markedly increased as compared with the other groups. Dietary carbohydrate source did not materially affect concentrations of stable zinc in the liver, kidneys, pancreas and residual carcass. PMID- 1638183 TI - Selenium intakes of children from Malawi and Papua New Guinea consuming plant based diets. AB - Dietary selenium intakes were determined over three seasons for 66 children aged 4-6 y in rural Malawi, and at one season for 67 children aged 6-10 y in rural Papua New Guinea. The selenium content of the foods consumed was assessed using instrumental neutron activation analysis. Median intakes of selenium for the Malawian children were 20 micrograms per day, 21 micrograms per day, and 15 micrograms per day at harvest, postharvest, and preharvest seasons, respectively. More than 43% of the Malawian intakes were below the U.S. Recommended Dietary Allowances for 4-6 y olds (20 micrograms per day). Median intake of Se for the Papua New Guinean children was 20 micrograms per day, with 87% of the intakes below the recommended level for 7-10 y olds (30 micrograms per day). Statistical comparisons of selenium intakes over three seasons for the 51 children present in all survey periods revealed that mean intakes were not significantly different in survey periods one and two, but decreased significantly in survey period three, when expressed per day (p less than 0.002), per MJ (p less than 0.003), or per kg (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1638184 TI - Relationships between myocardial macrominerals and trace elements and luminal narrowing of coronary arteries in Finnish children. AB - In addition to the traditional risk factors for cardiovascular diseases it has been hypothesized that a suboptimal intake of macrominerals and trace elements plays a role in the etiology of such diseases. We studied the possible correlation between preatherosclerotic changes in the coronary arteries and the myocardial concentration of K, Ca, Mg, Fe, Zn, Cu and Se in an autopsy series of children who had died mainly from accidental causes (n = 58). The concentrations of myocardial elements were comparable to values published elsewhere except for a slightly higher Cu concentration. The myocardial Se concentration indicated an adequate Se status. Narrowing of the coronary artery lumen was not correlated with myocardial element concentration except in the case of Se, for which a positive correlation was found (r = 0.23, p less than 0.04). Myocardial K was positively correlated with myocardial Mg (r = 0.65, p less than 0.001) and inversely correlated with Ca (r = -0.50, p less than 0.001). The intake of saturated vs. unsaturated fats was associated with myocardial Cu and Ca concentrations. Our results suggest that myocardial macrominerals and trace elements do not play a role in juvenile preatherosclerotic changes of the arteries. PMID- 1638185 TI - Review of publications. PMID- 1638186 TI - The use of animals in research. PMID- 1638187 TI - Spreading HIV is not an offence. PMID- 1638188 TI - Cholesterol lowering trials in coronary heart disease: frequency of citation and outcome. AB - OBJECTIVE: To see if the claim that lowering cholesterol values prevents coronary heart disease is true or if it is based on citation of supportive trials only. DESIGN: Comparison of frequency of citation with outcome of all controlled cholesterol lowering trials using coronary heart disease or death, or both, as end point. SUBJECTS: 22 controlled cholesterol lowering trials. RESULTS: Trials considered by their directors as supportive of the contention were cited almost six times more often than others, according to Science Citation Index. Apart from trials discontinued because of alleged side effects of treatment, unsupportive trials were not cited after 1970, although their number almost equalled the number considered supportive. In three supportive reviews the outcome of the selected trials was more favourable than the outcome of the excluded and ignored trials. In the 22 controlled cholesterol lowering trials studied total and coronary heart disease mortality was not changed significantly either overall or in any subgroup. A statistically significant 0.32% reduction in non-fatal coronary heart disease seemed to be due to bias as event frequencies were unrelated to trial length and to mean net reduction in cholesterol value; individual changes in cholesterol values were unsystematically or not related to outcome; and after correction for a small but significant increase in non-medical deaths in the intervention groups total mortality remained unchanged (odds ratio 1.02). CONCLUSIONS: Lowering serum cholesterol concentrations does not reduce mortality and is unlikely to prevent coronary heart disease. Claims of the opposite are based on preferential citation of supportive trials. PMID- 1638189 TI - Smoking and the young. PMID- 1638190 TI - Reducing home accidents in elderly people. PMID- 1638191 TI - Randomised controlled trial of azathioprine withdrawal in ulcerative colitis. AB - OBJECTIVE: To determine whether azathioprine can prevent relapse in ulcerative colitis. DESIGN: One year placebo controlled double blind trial of withdrawal or continuation of azathioprine. SETTING: Outpatient clinics of five hospitals. SUBJECTS: 79 patients with ulcerative colitis who had been taking azathioprine for six months or more. Patients in full remission for two months or more (67), and patients with chronic low grade or corticosteroid dependent disease (12) were randomised separately. 33 patients in remission received azathioprine and 34 placebo; five patients with chronic stable disease received azathioprine and seven placebo. MAIN OUTCOME MEASURE: Rate of relapse. Relapse was defined as worsening of symptoms or sigmoidoscopic appearance. RESULTS: For the remission group the one year rate of relapse was 36% (12/33) for patients continuing azathioprine and 59% (20/34) for those taking placebo (hazard rate ratio 0.5, 95% confidence interval 0.25 to 1.0). For the subgroup of 54 patients in long term remission (greater than six months before entry to trial) benefit was still evident, with a 31% (8/26) rate of relapse with azathioprine and 61% (17/28) with placebo (p less than 0.01). For the small group of patients with chronic stable colitis (six were corticosteroid dependent and six had low grade symptoms) no benefit was found from continued azathioprine therapy. Adverse events were minimal. CONCLUSIONS: Azathioprine maintenance treatment in ulcerative colitis is beneficial for at least two years if patients have achieved remission while taking the drug. Demonstration of the relapse preventing properties of azathioprine has implications for a large number of patients with troublesome ulcerative colitis, who may benefit from treatment with azathioprine. PMID- 1638192 TI - Farm accidents in children. AB - OBJECTIVE: To examine the problem of accidental injury to children on farms. DESIGN: Prospective county based study of children presenting to accident and emergency departments over 12 months with injuries sustained in a farm setting and nationwide review of fatal childhood farm accidents over the four years April 1986 to March 1990. SETTING: Accident and emergency departments in Aberystwyth, Carmarthen, Haverfordwest, and Llanelli and fatal accidents in England, Scotland, and Wales notified to the Health and Safety Executive register. SUBJECTS: Children aged under 16. MAIN OUTCOME MEASURE: Death or injury after farm related accidents. RESULTS: 65 accidents were recorded, including 18 fractures. Nine accidents necessitated admission to hospital for a mean of two (range one to four) days. 13 incidents were related to tractors and other machinery; 24 were due to falls. None of these incidents were reported under the statutory notification scheme. 33 deaths were notified, eight related to tractors and allied machinery and 10 related to falling objects. CONCLUSIONS: Although safety is improving, the farm remains a dangerous environment for children. Enforcement of existing safety legislation with significant penalties and targeting of safety education will help reduce accident rates further. PMID- 1638193 TI - Farm accidents in adults. PMID- 1638194 TI - Utilisation of medical care by abused women. PMID- 1638195 TI - Cutaneous vasculitis due to ciprofloxacin. PMID- 1638196 TI - Effect of iodinated water soluble contrast media on urinary protein assays. PMID- 1638197 TI - Adenosine and cardiac arrhythmias. PMID- 1638198 TI - Home accidents in older people: role of primary health care team. AB - OBJECTIVES: To determine the incidence and nature of unreported and reported home accidents in older people and to investigate associated environmental factors. DESIGN: Postal questionnaire requesting information on home accidents in the preceding month. SETTING: Inner London general practice. SUBJECTS: All registered patients aged over 65 years (n = 1662), of whom 120 were inappropriately registered and 1293 responded. MAIN OUTCOME MEASURE: Circumstances and consequences of accidents in the home. RESULTS: 108 accidents were recorded in 100 patients, giving a home accident rate of 84/1000 patients, equivalent to an annual rate of 1002/1000. 73 accidents were falls, and 83 were unreported. Of the 25 reported accidents, 19 were reported to general practice and six to accident and emergency departments (5.6% of all events). Rates of home accidents increased with age and were higher in women than men (79/819 upsilon 29/474; chi 2 = 4.5, df = 1, p less than 0.05). CONCLUSIONS: The incidence of home accidents in people aged over 65 years was high but few events were reported to medical services. General practice provided the main contact for patients who reported home accidents, and primary care workers have important opportunities for advising elderly patients on home accident prevention. Improved publicity on home safety targeted at older people and their carers would support the primary health care team in this role. PMID- 1638199 TI - The chains of education, experience, and culture. PMID- 1638200 TI - Drug management of ulcerative colitis. PMID- 1638201 TI - Non-Hodgkin's lymphoma. II: Management problems. PMID- 1638202 TI - Juvenile myoclonic epilepsy. PMID- 1638203 TI - Oesophageal achalasia in adolescent women mistaken for anorexia nervosa. PMID- 1638204 TI - ABC of colorectal diseases. Appendicitis. PMID- 1638205 TI - Awareness under anaesthesia. PMID- 1638206 TI - Awareness under anaesthesia. PMID- 1638207 TI - Risks associated with assisted conception. PMID- 1638208 TI - Cancer chemotherapy and fertility. PMID- 1638209 TI - Risks associated with assisted conception. PMID- 1638210 TI - Steroid receptors in early breast cancer. PMID- 1638211 TI - Diarrhoea. PMID- 1638212 TI - Hyponatraemia in children. PMID- 1638213 TI - Reversing vasectomy. PMID- 1638214 TI - Monitoring lithium treatment. PMID- 1638215 TI - Monitoring ambulatory blood pressure in general practice. PMID- 1638216 TI - Fulminant hepatitis B in infants. PMID- 1638217 TI - Hypercalcaemia in patients receiving dialysis. PMID- 1638218 TI - Hypercalcaemia in patients receiving dialysis. PMID- 1638219 TI - Breast feeding in developing countries. PMID- 1638220 TI - Day hospitals for elderly people. PMID- 1638221 TI - Epidemiological aspects of travel related illness. PMID- 1638222 TI - Gonad protection in young orthopaedic patients. PMID- 1638223 TI - Consultants' communications with general practitioners. PMID- 1638224 TI - Health and safety on the farm. PMID- 1638225 TI - Severe "silent" mitral regurgitation after myocardial infarction: a clinical conundrum. PMID- 1638226 TI - ABC of colorectal diseases. Lower gastrointestinal haemorrhage. PMID- 1638227 TI - Teaching vaginal examination. PMID- 1638228 TI - Teaching vaginal examination. PMID- 1638229 TI - Teaching vaginal examination. PMID- 1638230 TI - Management of breast cancer. PMID- 1638231 TI - Management of breast cancer. PMID- 1638233 TI - Babies' sleeping position. PMID- 1638232 TI - Management of breast cancer. PMID- 1638234 TI - Percutaneous endoscopic gastrostomy feeding. PMID- 1638235 TI - Percutaneous endoscopic gastrostomy feeding. PMID- 1638236 TI - Percutaneous endoscopic gastrostomy feeding. PMID- 1638237 TI - Percutaneous endoscopic gastrostomy feeding. PMID- 1638238 TI - Percutaneous endoscopic gastrostomy feeding. PMID- 1638239 TI - Psychosocial problems in epilepsy. PMID- 1638240 TI - Treating obesity in children. PMID- 1638241 TI - Harm minimisation for drug misusers. PMID- 1638242 TI - Farmer's hip. PMID- 1638243 TI - Farmer's hip. PMID- 1638244 TI - Making air crashes more survivable. PMID- 1638245 TI - Cite the workers. PMID- 1638246 TI - Health technology assessment. PMID- 1638247 TI - Giant cell arteritis. PMID- 1638248 TI - Polio eradication as 2000 approaches. PMID- 1638249 TI - Promoting sexual health. PMID- 1638250 TI - Service increment for teaching and research. PMID- 1638251 TI - Recruitment methods for screening programmes: trial of a new method within a regional osteoporosis study. AB - OBJECTIVE: To estimate the response rates and operating costs of three recruitment methods within a regional osteoporosis screening programme. DESIGN: Randomised trial of three types of invitation letter: one offering fixed appointments with option to change time, one offering fixed appointments but requiring telephoned confirmation of intention to attend, and one inviting recipient to telephone to make an appointment. SETTING: Osteoporosis screening unit, Aberdeen. SUBJECTS: 1200 women aged 45-49 years living within 32 km of Aberdeen and randomly selected from the community health index. 400 women were randomised to each appointment method. MAIN OUTCOME MEASURES: Numbers attending for screening; default rate among women who confirmed appointments; social class of attenders; cost per appointment slot and per completed scan. RESULTS: 299 (75%), 277 (69%), and 217 (54%) women were scanned after fixed, confirmable, and open invitations respectively. Women who attended were given a questionnaire, and 694 (87.5%) returned it. No significant differences were found in the social class of attenders among the three methods. Of the 514 women who made or confirmed appointments, 494 attended for a scan. Total costs per scan were 25.00 pounds, 21.40 pounds, and 21.00 pounds for fixed, confirmable, and open invitations respectively. CONCLUSIONS: The offer of a fixed appointment requiring telephoned confirmation has the potential to reduce the costs of scanning without exaggerating any social bias or significantly reducing response rates provided that empty appointments can be rebooked at short notice. PMID- 1638252 TI - Mild and moderate dyskaryosis: can women be selected for colposcopy on the basis of social criteria? AB - OBJECTIVE: To describe the distribution of cervical intraepithelial neoplasia grades among women with mild and moderate dyskaryosis after a single cervical smear and to determine whether social criteria could help identify women who are at increased risk of grade II or III disease. DESIGN: Cross sectional analysis within a randomised prospective study. Subjects had a repeat smear, a colposcopic examination, and an excision biopsy of the transformation zone. In addition, women were asked to complete a social questionnaire. SETTING: Colposcopy clinic, Aberdeen. SUBJECTS: 228 women with a single smear test showing mild or moderate dyskaryosis. MAIN OUTCOME MEASURES: Histology, age, sexual and contraceptive history, cigarette smoking. RESULTS: 159 (70%) women had cervical intraepithelial neoplasia grades II or III. Among current smokers the prevalence of grade II and III disease was higher in women who smoked greater than or equal to 20 cigarettes a day (84%) than among those who smoked less (66%; p less than 0.04). Women with more than one sexual partner also had a higher prevalence (75%) than women with only one partner (50%; p = 0.0028). Use of oral contraceptives and younger age were not significantly associated. The prevalence of grade II or III disease was up to 66% in the lower risk groups. CONCLUSIONS: Because of the high prevalence of cervical intraepithelial neoplasia grades II and III in both the high and the low risk groups social factors are not useful for selecting women with mild or moderate dyskaryosis for either early referral to colposcopy or cytological surveillance. PMID- 1638253 TI - Does the MRCGP examination discriminate against Asian doctors? AB - OBJECTIVE: To ascertain whether the membership examination for the Royal College of General Practitioners (MRCGP) discriminates against doctors of Indian subcontinent ethnic origin ("Asian doctors"). DESIGN: Retrospective analysis of data from five administrations of the MRCGP examination (December 1988-December 1990). SETTING: United Kingdom national examination body. SUBJECTS: 3686 doctors taking the examination for the first time, 244 of whom were classified as Asian, the remainder as non-Asian. MAIN OUTCOME MEASURES: Comparison of performance in each of the written and oral components of the examination between Asian doctors, identified by their names and classified into subgroups by countries of birth and primary medical training from data provided at registration, and non-Asian doctors. RESULTS: On written components of the examination (multiple choice paper mean score Asians versus non-Asians 42.3 v 48.6, modified essay paper 40.9 v 48.9, practice topic/critical reading paper 41.5 v 48.7, all p less than 0.001 by t testing). But analysis by countries of birth and primary training showed that these differences were due largely to poor performance by certain groups of Asian doctors, especially those born and trained in the Indian subcontinent or elsewhere outside the United Kingdom. Asian doctors born and trained in the United Kingdom and those born in Africa or the West Indies and trained in the United Kingdom performed similarly to the non-Asian doctors. CONCLUSIONS: The examination does not systematically discriminate against Asian doctors, but the poor performance of the two subgroups of Asians is cause for serious concern and requires investigation. PMID- 1638254 TI - King's model for allocating service increment for teaching and research (SIFTR). PMID- 1638255 TI - Hodgkin's disease--I: Identification and classification. PMID- 1638256 TI - Dynamics and topology of idiotypic networks. AB - Jerne's idiotypic network was previously modelled using simple proliferation dynamics and a homogeneous tree as a connection structure. The present paper studies analytically and numerically the genericity of the previous results when the network connection structure is randomized, e.g., with loops and varying connection intensities. The main feature of the dynamics is the existence of different localized attractors that can be interpreted in terms of vaccination and tolerance. This feature is preserved when loops are added to the network, with a few exceptions concerning some regular lattices. Localized attractors might be destroyed by the introduction of a continuous distribution of connection intensities. We conclude by discussing possible modifications of he elementary model that preserve localization of the attractors and functionality of the network. PMID- 1638257 TI - Ising model for B-Z transition in supercoiled DNA. AB - The possible existence of nucleic acids in right-handed and left-handed helical forms is considered. A statistical mechanical model is developed to obtain an expression for a change in twist during helical transformation in terms of corresponding free energies and linking for a supercoiled DNA. The theoretically predicted values are compared with those determined experimentally. The physico chemical significance of the parameters is discussed. PMID- 1638258 TI - Vaccination in density-dependent epidemic models. AB - This paper examines the effect of vaccination for an epidemic model where the death rate depends on the number of individuals in the population. The basic model which is described is based on measles or other childhood diseases in developing countries or viral diseases such as rabies in animal populations. An equilibrium analysis of the model and the local stability of small perturbations about the equilibrium values are discussed. The biological implications of these results are examined and similar results presented for modifications of the basic model. PMID- 1638259 TI - Tree asymmetry--a sensitive and practical measure for binary topological trees. AB - The topological structure of a binary tree is characterized by a measure called tree asymmetry, defined as the mean value of the asymmetry of its partitions. The statistical properties of this tree-asymmetry measure have been studied using a growth model for binary trees. The tree-asymmetry measure appears to be sensitive for topological differences and the tree-asymmetry expectation for the growth model that we used appears to be almost independent of the size of the trees. These properties and the simple definition make the measure suitable for practical use, for instance for characterizing, comparing and interpreting sets of branching patterns. Examples are given of the analysis of three sets of neuronal branching patterns. It is shown that the variance in tree-asymmetry values for these observed branching patterns corresponds perfectly with the variance predicted by the used growth model. PMID- 1638260 TI - Poisson, compound Poisson and process approximations for testing statistical significance in sequence comparisons. AB - DNA and protein sequence comparisons are performed by a number of computational algorithms. Most of these algorithms search for the alignment of two sequences that optimizes some alignment score. It is an important problem to assess the statistical significance of a given score. In this paper we use newly developed methods for Poisson approximation to derive estimates of the statistical significance of k-word matches on a diagonal of a sequence comparison. We require at least q of the k letters of the words to match where 0 less than q less than or equal to k. The distribution of the number of matches on a diagonal is approximated as well as the distribution of the order statistics of the sizes of clumps of matches on the diagonal. These methods provide an easily computed approximation of the distribution of the longest exact matching word between sequences. The methods are validated using comparisons of vertebrate and E. coli protein sequences. In addition, we compare two HLA class II transplantation antigens by this method and contrast the results with a dynamic programming approach. Several open problems are outlined in the last section. PMID- 1638261 TI - The study of combined action of agents using differential geometry of dose-effect surfaces. AB - Although graphic surfaces have been used routinely in the study of combined action of agents, they are mainly used for display purposes. In this paper, it is shown that useful mechanistic information can be obtained from an analytical study of these surfaces using the tools of differential geometry. From the analysis of some simple dose-effect surfaces, it is proposed that the intrinsic curvature, referred to in differential geometry as the Gaussian curvature, of a dose-effect surface can be used as a general criterion for the classification of interaction between different agents. This is analogous to the interpretation of the line curvature of a dose-effect curve as an indication of self-interaction between doses for an agent. In this framework, the dose-effect surface would have basic uniform fabric with zero curvature in the absence of interaction, tentatively referred to as null-interaction. Pictorially speaking, this fabric is distorted locally or globally like the stretching and shrinking of a rubber sheet by the presence of interaction mechanisms between different agents. Since self interaction with dilution dummies does not generate intrinsic curvature, this criterion of null-interaction would describe the interaction between two truly different agents. It is shown that many of the published interaction mechanisms give rise to dose-effect surfaces with characteristic curvatures. This possible correlation between the intrinsic geometric curvature of dose-effect surfaces and the biophysical mechanism of interaction presents an interesting philosophical viewpoint for the study of combined action of agents. PMID- 1638262 TI - Stochastic models for toxicant-stressed populations. AB - We obtain conditions for the existence of an invariant distribution on (0, infinity) for stochastic growth models of Ito type. We interpret the results in the case where the intrinsic growth rate is adjusted to account for the impact of a toxicant on the population. Comparisons with related results for ODE models by Hallam et al. are given, and consequences of taking the Stratonovich interpretation for the stochastic models are mentioned. PMID- 1638264 TI - Behaviour rehabilitation of the challenging client in less restrictive settings. AB - Individuals who have sustained traumatic brain injury may provide friends, family, and rehabilitation professionals with challenges through an increased likelihood of their engaging in socially inappropriate behaviours. At extremes the inappropriate behaviours include vocal and physical assault, non-compliance, self-injurious behaviours, elopement, and property destruction. While these maladaptive behaviours are by themselves troublesome, for some individuals they provide severe barriers to rehabilitation. One option for the challenging rehabilitation client is a neurobehavioural programme, typically offering an access-limited or otherwise secure physical environment and which focuses on behaviour reduction. While outcomes from neurobehavioural programmes are typically positive, their expense and the negative connotations of this type of programme will at times dissuade family members from enrolling the client. We describe an alternative, less restrictive behavioural programme operated in the physical and social context of a larger, more typical community-based rehabilitation programme for traumatically brain-injured individuals. This programme has been in operation for nearly three years, successfully serving more than 200 clients, of which approximately 20% posed behaviour management problems. Identified variables accounting for these successes include: formal guidelines for programme development, staff training and monitoring, data collection, integration of an interdisciplinary team, discharge planning and post-discharge follow-up. We provide a general programme description followed by discussions of four brief case studies to illustrate basic principles of the programme. Programme strengths are discussed, as are constraints placed on the programme by the physical and social environments in which it operates. PMID- 1638263 TI - On the kinetics and optimal specificity of cytotoxic reactions mediated by T lymphocyte clones. AB - Using the chromium release assay and the single cell assay in agarose, we study the cytotoxic reaction of the MHC-restricted T lymphocyte clones P89:15 and P1:3, which recognize distinct but specific tumour antigens on the surface of syngeneic P815 mastocytoma cells. We propose a mathematical model which describes these experiments, accounts for the strongly non-Michaelian behaviour of the reaction and permits us to estimate the kinetic parameters characterizing effector-target conjugation and lethal hit delivery. The results show that the binding and lytic activity of effector cells is modulated by the number of targets bound to them. The binding of a second target by an effector having already a target bound is facilitated; on the other hand, an effector having bound two targets delivers a lethal hit more slowly than one with a single target bound. We investigate the role of these kinetic properties in the competition between the process of tumour progression due to cancer cell replication and the process of tumour regression due to T lymphocyte cytotoxic activity. For both clones, we estimate the effector target ratio beyond which rejection prevails. This ratio is nine times larger for P1:3 than for P89:15. Furthermore, our analysis suggests that there exists an optimal specificity minimizing this ratio. Deviations from this optimum, be it in the sense of an increase or decrease of specificity, tends to stabilize the tumoural state: a situation which in the broader context of the immune response evolution and regulation can be viewed as an immune response dilemma. PMID- 1638265 TI - Fluoxetine as a treatment for emotional lability after brain injury. AB - Emotional lability or emotionalism is a relatively common phenomenon and frequently occurs following vascular or traumatic brain injury. It is distressing and embarrassing to sufferers and their families, and often interferes with rehabilitation. At present there is no satisfactory or reliable treatment for this condition. We describe an open trial using fluoxetine, a newer antidepressant with a specific serotonergic action, in the treatment of emotional lability due to brain injury. Six consecutive cases of emotional lability attending a rehabilitation unit were studied (five cases of cerebrovascular accident and one of traumatic brain injury). Response to treatment was measured using a modification of the scale described by Lawson and MacLeod [1]. All showed a marked improvement within one week of commencing fluoxetine and the drug was well tolerated with no reported side-effects. The speed of onset and degree of improvement suggest that fluoxetine may be a useful agent in the treatment of emotional lability due to brain injury. Our observations indicate that further investigation of the role of fluoxetine in the treatment of emotional lability is warranted. PMID- 1638266 TI - Problems and changes after traumatic brain injury: differing perceptions within and between families. AB - This study is an attempt to characterize subgroups of families based on differing perceptions of problems and changes after traumatic brain injury. The Problem Checklist of the NYU Head Injury Family Interview was administered to 34 people with head injuries (PHI), and a significant other (SO) of each, between 1 and 3 years post-injury. Families were found to differ systematically in their responses and could be divided into three groups: High Agreement group (HAF), where there was high agreement between the PHI and the SO regarding problems and changes; High Disagreement--PHI endorsing more problems than the SO (HD-PHI); and High Disagreement--SO endorsing more problems than the PHI (HD-SO). No differences were found between these groups in age, sex, duration of coma, time since injury, educational achievement of the PHI, or the SO's relationship to the PHI. However, the HD-PHI group tended to have a higher return-to-work rate, the SOs in the HAF group reported the highest rates of subjective burden, and groups were found to differ in types of items endorsed by the PHI v. the SOs. Implications of findings are discussed regarding reliability of reporting problems, awareness issues in return to work and subjective burden of family members, and methodological and treatment issues. PMID- 1638267 TI - Effect of blood alcohol level on recovery from severe closed head injury. AB - A retrospective archival study of 129 moderate to severe closed head-injury patients from a university-based rehabilitation hospital was conducted to investigate the effect of blood alcohol level (BAL) at time of trauma on the length of post-traumatic amnesia (PTA), length of hospitalization and cognitive status on clearing PTA. While no statistical significance was obtained for the effect of BAL on length of PTA, a mean difference of 15.4 days between 'no alcohol' and 'intoxicated' patient groups was observed. A low, but significant correlation, r = 0.249, p less than 0.05, indicated that as blood alcohol level increased, time to rehabilitation admission increased. The sex of the patient had a significant effect on length of PTA, BAL and time of recovery variable F (6,81) = 2.468, p less than 0.05. Females experienced longer length of PTA, but had lower BALs than males. Measures of cognitive status on clearing PTA did not show a statistically significant effect of BAL. Results are discussed in terms of mediating variables in the relationship between BAL and the length of acute hospitalization, prolonged PTA in patients with a positive BAL, and potential physiological bases for the interaction among sex, BAL and PTA duration. PMID- 1638268 TI - Superior mesenteric artery syndrome: an unusual cause of intestinal obstruction in brain-injured children. AB - Superior mesenteric artery syndrome is a rare cause of upper intestinal obstruction in both adults and children. Sixteen children with severe traumatic brain injury and spastic quadriparesis developed small intestinal obstruction while undergoing a rehabilitation programme between 1981 and 1990. Five patients met the roentgenographic diagnostic criteria. The presenting symptom was post prandial bilious vomiting. The mean age was 13 (10-16) years. The mean time clapsed from injury to diagnosis was 53 days and from rehabilitation admission to diagnosis 22 days. The mean delay in diagnosis after onset of symptoms was 4 days. All patients were of disproportionately lower body weight in relation to height, with a mean weight loss of 7 kg. The mean percentile for weight was 18 and height 58, with a difference of 30 between height and weight percentiles. The patients were receiving nasogastric or gastrostomy tube feedings at the onset of the symptoms. All patients were treated non-surgically with gastric aspiration, nasojejunal or gastrojejunal feeding by passing a feeding tube distal to obstruction. No patient required intravenous hyperalimentation. There was no recurrence in any patient during the follow-up period of 1-5 years. Though rare, superior mesenteric artery syndrome can develop in brain-injured children with spastic quadriparesis, prolonged recumbency and recent weight loss. Increased awareness of occurrence of this condition and timely management will decrease morbidity and complications that may interfere with recovery. PMID- 1638269 TI - Epidemiological findings in traumatic post-comatose unawareness. AB - We have examined the epidemiological background of 134 consecutive patients admitted to our centre who suffered from post-traumatic unconsciousness of over 1 month's duration. The incidence of such unconsciousness in Israel is estimated as 4 per 1,000,000, or one case in 410 hospitalizations for head trauma. The cause of trauma was a road accident in 69% of cases. Among victims, pedestrians and cyclists were more likely than four-wheeled vehicle drivers and their passengers to suffer from prolonged unconsciousness, from which they were less likely to recover. PMID- 1638270 TI - Functional improvement in severe head injury after readmission for rehabilitation. AB - Early rehabilitation has been shown to minimize complications and optimize functional outcomes in head-injured patients. Although cognitive, behavioural and vocational issues continue for years after injury, many investigations maintain that physical improvement is limited after 6 months. At 12 months after injury, expectations for physical improvement are generally limited. In addition, although repeated inpatient admissions for rehabilitation are common, gains in self-care and mobility skills during readmissions for rehabilitation have not been specifically investigated. In this retrospective study the records of 49 severely head-injured patients were evaluated. All were readmitted to an inpatient rehabilitation facility more than 12 months after injury. Barthel Index scores were obtained to evaluate physical function. Although previous studies would predict few improvements, in this study 53% (26 patients) showed improvement, and the difference between readmission and discharge Barthel scores was statistically significant (p = 0.0001). Gains were highly correlated with length of readmission, but not with age of patient, age at time of injury, length of coma, time since injury, or duration of previous rehabilitation. Patients with mid-range admission Barthel scores (21-85) demonstrated the largest gains, with 79% showing improvement. Gains averaged 11.2 points on the Barthel Index. Severely head-injured patients may show clinically significant improvement in physical function well after current standards predict a plateau. PMID- 1638271 TI - Post-traumatic amnesia and Glasgow Coma Scale related to outcome in survivors in a consecutive series of patients with severe closed-head injury. AB - A consecutive series of 93 severe closed-head injury (SCHI) patients, discharged from hospital in a conscious state, were rated on the Glasgow Outcome Scale at 6 and 12 months post-injury. Patients were included in this study if they had a period of post-traumatic amnesia (PTA) exceeding 24 h. Approximately 80% of patients had made a good recovery by 12 months post-injury; a better outcome than has been found in studies using the presence of coma during the first 6 h post admission to hospital to define severe head injury. When analysed individually, duration of PTA and Glasgow Coma Scale scores on admission to hospital were both strongly correlated with outcome. Only duration of PTA, however, contributed significantly to outcome variance when potential outcome predictors were assessed using a stepwise multiple regression analysis. The definition of severe head injury, the higher than usual incidence of good recovery in the present study, and the relationship between injury severity and outcome are discussed. PMID- 1638272 TI - The Simulation Index: a reliability study. AB - The Simulation Index was derived from 15 error types on the WAIS-R and WMS occurring with a high degree of specificity in a criterion simulation group (n = 16) and a further five error types specific to a group of patients sustaining severe head injury (n = 16). The reliability of the scoring criteria was evaluated in terms of the rate of agreement in scoring for the presence or absence in each of the 20 error types achieved by two independent neuropsychologists. Percentage agreement rates for each of the 20 error types ranged between 83 and 100%. When identification of group membership was attempted on the basis of simple inspection of the test protocols, diagnostic hit rates were at chance level. When identification of group membership was based on Simulation Index cut-off scores, each of the raters achieved a diagnostic hit rate of 94% for each of the simulation and head-injury group patients. The results support the reliability and clinical utility of the Simulation Index. PMID- 1638273 TI - Neural changes in acute arthritis in monkeys. I. Parallel enhancement of responses of spinothalamic tract neurons to mechanical stimulation and excitatory amino acids. AB - Somatosensory neurons of the spinal cord, including projection neurons, become hyperexcitable to mechanical stimuli during the development of experimental arthritis in rats and cats and hence are suggested to participate in the generation of arthritic hyperalgesia in humans. The experiments described here show a potentiation of the responses of spinothalamic tract (STT) neurons in monkeys during the development of an acute arthritis. The results demonstrate that the responses of STT neurons to mechanical stimuli and to iontophoretically applied excitatory amino acids (EAAs), particularly those acting at non-N-methyl D-aspartate (non-NMDA) receptors, become enhanced during the development of inflammation produced by intra-articular injection of kaolin and carrageenan. Since the enhancement of both responses follows a similar time course, the results of this work suggest a role for EAAs in the hyperalgesia associated with arthritis and hence may provide a possible pharmacologic target for alleviation and/or prevention of arthritic pain. PMID- 1638274 TI - Neural changes in acute arthritis in monkeys. IV. Time-course of amino acid release into the lumbar dorsal horn. AB - Extracellular levels of amino acids were measured during the development of experimental arthritis in anesthetized monkeys. Levels of glutamate, aspartate, glycine, serine, glutamine, taurine, cysteic acid and asparagine were each measured in consecutive 30 min samples before, during and for several hours after injection of kaolin and carrageenan into the articular capsule of one knee. Samples were obtained via a microdialysis probe placed in the lumbar dorsal horn ipsilateral to the injected knee and assayed using HPLC with fluorescence detection. Glutamate, aspartate, glycine and serine increased transiently following intra-articular injection of inflammatory agents. During this period glutamine levels decreased. A second phase of release then occurred which included more prolonged changes in amino acid levels that were sometimes of greater magnitude than those immediately following the injection. In animals which were later observed to have depletion of SP in the dorsal horn of the inflamed side, taurine levels increased starting after the Glu, Asp and Gly had plateaued at near baseline concentrations. Thus during the first stages of joint inflammation EAAs are released into the dorsal horn, followed by increased levels of IAAs, possibly representing activation of the descending endogenous analgesia system. This phase is followed by a semiacute response consisting in part of increased extracellular levels of SP and Tau. While SP is presumably part of an ascending nociceptive transmission system, Tau could be part of a second system aimed at reducing excessive neural activity including neural transmission resulting in intense maintained pain. PMID- 1638275 TI - Vestibular influences on the sympathetic nervous system. AB - Studies using both electrical and natural stimulation have established that the vestibular system has prominent effects on sympathetic outflow and blood pressure. Preliminary evidence suggests that receptors in both otolith organs and semicircular canals are involved in producing these effects. Furthermore, vestibulosympathetic reflexes appear to be mediated by the medial vestibular nucleus and slowly conducting projections from the rostral ventrolateral medulla and caudal medullary raphe nuclei to preganglionic neurons in the thoracic spinal cord. However, many details are missing from our knowledge and understanding of the functional significance and neural substrate of vestibular influences on the sympathetic nervous system. PMID- 1638276 TI - Brain macrophages: evaluation of microglia and their functions. AB - There is now evidence approaching, if not having already surpassed, overwhelming in support of microglial cells as macrophages. Consistent with this cellular identity, they appear to arise from monocytes in developing brain where amoeboid microglia function in removing cell death-associated debris and in regulating gliogenesis. In normal adult tissue, ramified microglial cells with down regulated macrophage functional properties may serve a constitutive role in cleansing the extracellular fluid. Under all conditions of brain injury, microglia appear to activate and convert into active macrophages. Activated and reactive microglia participate in inflammation, removal of cellular debris and wound-healing, the latter through regulation of gliosis in scar formation and a potential contribution to neural regeneration and neovascularization. In the activated state, microglia also express MHC's and, thus, may function in antigen presentation and lymphocyte activation for CNS immune responses. As uniquely adapted tissue resident macrophages within the CNS, microglia serve a variety of functional roles over the lifespan of this tissue. These cells may therefore be involved in or contribute to some disease states; such has been indicated in multiple sclerosis and AIDS dementia complex. PMID- 1638277 TI - Protective effect of antibiotics on mortality risk from acute respiratory infections in Mexican children. AB - A case-control study of mortality from acute respiratory infections (ARI) among children under five years of age was conducted in Naucalpan, an urban-suburban area of Mexico City, and in rural localities of Tlaxcala, Mexico. The study found that ARI deaths tended to occur in the poorest neighborhoods; 78% of the deceased study subjects were infants under six months old; and 68% of the deaths occurred at home. Comparison of the data for cases (fatalities) and control children who had severe ARI but recovered showed that failure to receive antibiotics was associated with death (odds ratio 28.5, 95% confidence interval 2.1-393.4). This antibiotic effect was controlled for numerous potentially confounding factors. It is evident that antibiotics had a much greater effect in the early days of the illness than later on. In general, the findings strongly support PAHO/WHO primary health care strategies--including such strategies as standardized management of severe ARI cases--that seek to reduce childhood ARI mortality. PMID- 1638278 TI - Installation of a water disinfection system in a Mexico City hospital. AB - With a view to evaluating a small-scale water disinfection system based on production and application of oxidizing gases, the level of equivalent residual chlorine and the degree of contamination by fecal and total coliform bacteria was assessed at various points in the drinking water system of a Mexico City hospital before and after installation of the disinfection equipment. Tests done in May and June 1989, prior to installation of the equipment, showed that residual chlorine concentrations were lower than the national standard in most of the samples and that a sizable portion of these samples were also contaminated with fecal and total coliform concentrations exceeding national standards. After installation of the disinfection system at the main inflow to the hospital's drinking water supply in August 1989, the equivalent residual chlorine concentrations were found adequate and no coliform bacteria were detected. These results indicate that the oxidant mixture generated by the newly installed system was effectively disinfecting the water. PMID- 1638279 TI - Maternal and infant feeding practices in rural Bolivia. AB - Seventy-four members of mothers' clubs in a rural area outside of La Paz, Bolivia, were interviewed in order to learn more about maternal and infant nutritional practices and use of child health services. Most of the women used a combination of western and traditional child health services, though a substantial percentage used only traditional services. Almost all of their deliveries were attended solely by family members, most notably the pregnant woman's husband. All the interviewed mothers breast-fed their infants, although most gave them other prelacteal liquids in the immediate postpartum period. Breast milk supplementation generally began when the infants were between four and eight months old, occasionally later. Most of those interviewed said they stopped breast-feeding when they knew they were pregnant again; some continued breast-feeding through all or part of the pregnancy; only a small number stopped breast-feeding before they knew that they were pregnant. Almost all the women increased their food intake when they were breast-feeding, primarily by consuming additional liquids. These findings suggest that some current maternal and infant nutritional practices in the study area (such as universal breast-feeding and increased consumption of liquids by lactating mothers) should be encouraged, while others (particularly prelacteal feeding of liquids other than breast milk and late supplementation) should be discouraged. Both traditional and western health providers should be mobilized to perform this task. PMID- 1638280 TI - Serologic screening for Trypanosoma cruzi among blood donors in central Brazil. AB - The study reported here compares results obtained by blood banks screening sera for chagasic (Trypanosoma cruzi) infection with results obtained by the Chagas' Disease Reference Laboratory of the Federal University of Goias in Goiania, Brazil. It also evaluates results obtained using the ELISA technique to screen the study sera. The survey used data from six of eight blood banks serving the city of Goiania, an urban region of Central Brazil where Chagas' disease is highly endemic. The survey population consisted of 1,513 voluntary first-time blood donors whose donations occurred between October 1988 and April 1989. This group included 50% of all the first-time blood donors in that period. The six participating blood banks, which accounted for about 90% of all blood donations in Goiania during the study period, routinely used indirect hemagglutination (IHA) and complement fixation (CF) tests to screen sera for antibodies to T. cruzi. Comparison of the results provided by the blood banks with the reference laboratory's results indicated a relative sensitivity of 77%, which ranged from 50% to 100% depending on the blood bank studied. The comparison, which found 12 false negative results, indicated that transfusions of infected blood might have occurred despite the serologic screening performed by the blood banks. Relative to the standard of positivity established for the study, the enzyme-linked immunosorbent assay (ELISA) technique was found to have a sensitivity of 96.3%. Considering as positive only those sera yielding positive IHA and indirect immunofluorescence (IIF) test results, the ELISA technique yielded 2 false negative and 41 false positive responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1638281 TI - Cysticercosis: first 12 months of reporting in California. AB - Cysticercosis, a sometimes fatal ailment caused by larvae of the pork tapeworm Taenia solium, became a reportable disease in California in 1989. During the first year, from 1 April 1989 through 31 March 1990, 134 cases were reported to the California Department of Health Services. All of the 112 patients for whom laboratory diagnostic test data were obtained had neurocysticercosis. Nearly all (117) of the 127 patients whose race and ethnic background were known had a Hispanic background, and most of the 112 patients whose country of birth or prior residence was known had immigrated from T. solium-endemic countries. However, three of 11 patients born in the United States said they had never traveled outside the country, and it appears possible that indigenous transmission has been occurring. These findings affirm that neurocysticercosis should be included in the differential diagnosis of neurologic symptoms in patients who have immigrated from or traveled to T. solium-endemic countries, and also in those who have been in close contact with immigrants from endemic countries. PMID- 1638282 TI - Cost-benefit analysis of a regional system for vaccination against pneumonia, meningitis type B, and typhoid fever. AB - In early 1989 PAHO began examining a proposal for a regional program that would develop and disseminate vaccines of particular interest to its Member Countries. As part of that examination, a cost-benefit analysis was performed. That general analysis, presented here, sought to point up key factors that would strongly influence whether or not the program's benefits outweighed its costs. The program's two fundamental components, vaccine development and vaccine administration, were evaluated separately. Using a discount rate (r) of 10%, 10 year vaccine development costs were estimated at US$80.3 million in constant dollars. It was felt that enough people (at least 19.5 million a year) would be vaccinated so that the program would benefit from economics of scale. The total discounted number of vaccinations administered over a 20-year period was expected to be in the range of 400 to 506 million. Using these figures, estimates were made of the maximum that could be spent on vaccine administration without exceeding anticipated benefits. Considering only treatment costs saved through vaccination, assuming all sick people were treated, the ceiling cost for vaccinating one person against one target disease would be in the range of US$0.52-0.58. Even if not all the sick were treated, however, the Regional Vaccine System (SIREVA) would still appear justified if the benefits per disease case prevented were found to average between US$1,000 and US$2,000. Even so, it should be noted that these estimates are subject to a good deal of additional variation because of uncertainties regarding the worth of many elements evaluated -including the costs of lost work time, disability, and mortality--and because some of the elements involved--such as pain, suffering, and death--fall outside the purely economic realm. PMID- 1638283 TI - Tobacco or health: status in the Americas, 1992. PMID- 1638284 TI - Wound healing in foetal sheep: a histological and electron microscope study. AB - A study was made of the healing of excised, unsutured and sutured skin wounds in foetal sheep of 75, 90 and 120 days gestation and of wounds in newborn lambs and adult ewes. Foetal and postnatal wounds were found to heal in a very similar way. At each stage of development studied, excised wounds contract rapidly and histological and electron microscope examination demonstrates formation of granulation tissue and its maturation to scar tissue in all types of wound. Examination of polyvinyl sponges 7 and 14 days after subcutaneous implantation confirms the ability of foetal sheep to form vascularised scar tissue. The cellular inflammatory response to wounding is much less prominent in foetal than in postnatal sheep, the number and type of extravascular cells reflecting the changes in blood leucocyte content during development. From a very early stage foetal sheep react to insoluble irritants by the formation of multinucleate giant cells. PMID- 1638285 TI - A comparison of heparinised saline irrigation solutions in a model of microvascular thrombosis. AB - The use of heparinised irrigation solutions has become common in microvascular surgery, but the concentration of heparin has been determined empirically. A laboratory model of microvascular thrombosis, employing a crush injury, intimal abrasion, and stasis to the rat superficial femoral artery was used to compare heparinised saline irrigation solutions of various concentrations. The solutions included normal saline (Group I, controls) and heparinised normal saline in concentrations of 10 U/ml (Group III), 250 U/ml (Group IV), and 500 U/ml (Group V). Group I animals had a patency rate of 25% at 20 min and 0% at 24 h. Group II showed a patency rate of 75% at 20 min but fell to 37.5% at 24 h. Patency in Group III was 87.5% at 20 min and at 24 h. Group IV had a 100% patency rate at 20 min and at 24 h. Group V animals were 100% patent at 20 min and 87.5% patent at 24 h. The activated partial thromboplastin time was prolonged in animals exposed to 250 U/ml and 500 U/ml of heparinised saline. Patency was significantly improved in animals exposed to 100 U/ml, 250 U/ml and 500 U/ml when compared to the control group (p less than 0.001). These results suggest that topical heparinised saline administration is of benefit in the prevention of microvascular thrombosis. Higher concentrations tested in this study resulted in a significant increase in patency, but also prolonged the activated partial thromboplastin time. 100 U/ml is the ideal concentration of heparinised saline irrigation because it significantly improved patency but did not produce detectable systemic effects in this model. PMID- 1638286 TI - An in vitro study on the effect of UVA radiation on human gingival fibroblasts. AB - The recent availability of a 99.9% UVA source has made possible studies that show that low energy wavelengths, previously considered innocuous, significantly affected wound healing in hairless guinea pigs. Decreased wound tensile strength and a slower rate of wound contraction in irradiated animals were among the changes noted. Because of their advocated role in the wound healing process, fibroblasts were chosen to study the effects of pure UVA exposure at a cellular level. 3H-thymidine uptake levels were measured in 8 groups of fibroblast cultures (12 samples/group). The cultures were exposed to varying concentrations of pure UVA. Previously incorporated 14C-thymidine levels were used to compensate for differences in cell numbers between samples. At a fluence of 3.65 x 10(-3) watts/cm2, a significant decrease in 3H-thymidine incorporation (compared to controls) was seen for all exposure periods and there was a dose-dependent decrease only in 3H-thymidine uptake for cells exposed to 1-4 min of UVA. Using post-exposure incubations of 2-16 h, a time-dependent recovery of 3H-thymidine uptake was also demonstrated, from 40% of control at 4 h, to 75% at 8 h, and 99% at 16 h. The near-complete recovery at 16 h was seen in exposures up to 2.73 joules/cm2 (12 min), whereas higher concentrations showed only partial recovery. These studies demonstrated the deleterious, though reversible, effects of UVA on fibroblasts and suggest a possible pathophysiologic process for UVA's effect on wound healing in this animal model. PMID- 1638287 TI - New grafts for old? A review of alternatives to autologous skin. AB - Immediate resurfacing of skin defects is a challenging prospect, especially in patients with extensive full-thickness burns. Currently, split-thickness autografts offer the best form of wound coverage, but limited donor sites and their associated morbidity have prompted the search for alternatives. The application of allogeneic skin is restricted by availability and the risk of transmission of infection, whilst synthetic skin substitutes are simply expensive dressings. The problems of limited expansion may be overcome by culturing keratinocytes in vitro. Unlike autologous cells, allogeneic keratinocytes are available immediately, although they survive for less than a week when applied to full-thickness skin defects. Moreover, the absence of a dermal component in these grafts predisposes to instability and contracture. A cross-linked collagen and glycosaminoglycan dermal substitute, covered with thin split-skin grafts or cultured autologous keratinocytes, shows promise in burns patients. An alternative is a collagen matrix populated by allogeneic fibroblasts and overlaid with cultured autologous or allogeneic keratinocytes. The clinical application of cultured grafts remains imperfect but offers the prospect of immediate coverage and massive expansion. PMID- 1638288 TI - A vascularised rib strut technique for funnel chest correction. AB - We have refined the Ravitch technique of sternal elevation for surgical correction of funnel chest. Our major modification is introducing a living rib strut for supporting the elevated sternum. The left 5th rib with a vascular pedicle from the internal thoracic artery is turned 180 degrees beneath the sternum. We have used this method in 10 cases. The results have all been satisfactory. PMID- 1638289 TI - Improved chest wall fixation for correction of pectus excavatum. AB - Pectus excavatum, the most common congenital chest wall abnormality, is manifested by deformity of the costal cartilages resulting in a depressed and often rotated sternum. Although there are conflicting data to support and reject the concept that physiologic improvement can be a consequence of surgical repair, correction is frequently indicated for aesthetic improvement alone. The most popular current repair involves resection of abnormal costal cartilages, sternal osteotomy and mobilisation, followed by fixation of the sternum in the corrected position. Improved fixation techniques have evolved, but generally have not employed current concepts of rigid fixation. The correction of pectus excavatum using reconstruction plates incorporates the benefits of rigid fixation, while allowing custom chest wall contouring and sternal reorientation. Reconstruction plate fixation of the sternum should be considered during correction of pectus excavatum in adult and adolescent patients. PMID- 1638290 TI - Intra- and postoperative steroid injections for keloids and hypertrophic scars. AB - Treating keloids and hypertrophic scars is difficult. Here we report our method of treating recurrent keloid and hypertrophic scars. This involves surgical excision associated with intraoperative steroid injection, followed by routine weekly steroid injections for 2-5 weeks dependent on clinical signs and symptoms (pain, pruritus or paraesthesia), and monthly injections for another 3-6 months. The preliminary results thus far are promising. PMID- 1638292 TI - A bipedicled neurovascular step-advancement flap for soft tissue lengthening in clinodactyly. AB - Recommendations for the surgical treatment of clinodactyly have centered on techniques of osteotomy with or without bone grafting. However, the limiting factor to the correction may be tension in the soft tissues. A new technique to correct clinodactyly is described utilising an opening wedge osteotomy and bone grafting plus a bipedicled neurovascular step-advancement flap to correct the soft tissue deficiency. The procedure has been performed in five cases. PMID- 1638291 TI - Evaluation of various methods of treating keloids and hypertrophic scars: a 10 year follow-up study. AB - An attempt was made to assess the value of beta radiation alone or in combination with surgery, and of intralesional triamcinolone acetonide in treating 100 keloids and hypertrophic scars in 65 patients. Beta radiation alone was found to be effective in the eradication of symptoms (55% symptomatic relief), while results in the reduction of size of lesions have been poor (11% success rate). Surgery combined with postoperative beta radiation therapy yielded a 67% success rate. The success rate was 75% when radiation was delivered within 48 h of surgery. Preoperative radiation was found to be of no advantage. Intralesional triamcinolone acetonide produced symptomatic relief in 72% and complete flattening in 64% of the lesions. PMID- 1638293 TI - Organisation of cleft lip and palate services--results of a questionnaire. PMID- 1638294 TI - Extracorporeal tissue transfer for intra-oral reconstructions. AB - After the introduction of the concept of extracorporeal tissue transfer by the author in 1988, the technique has gained world wide acceptance and popularity. However it has not been used intraorally and in this paper we present its use in three very difficult intra-oral reconstructions. The technique is presented along with the results, and the merits discussed. PMID- 1638295 TI - A modified Le Fort I osteotomy for maxillofacial deformity: a preliminary report. AB - A new technique of Le Fort I osteotomy using a wedge-shaped bony incision is described. After forward mobilisation of the osteotomised maxilla, the bone graft is held firmly in contact under some compression between the maxilla and the mobilised wedged portion to achieve greater stability. This is a very effective technique for those maxillary osteotomies which need bone graft stabilisation, such as in cleft lip and palate patients. PMID- 1638296 TI - Relationship between intracranial pressure and intracranial volume in craniosynostosis. AB - Premature fusion of cranial sutures in craniosynostosis has been thought to lead to craniostenosis, which in turn may lead to increased intracranial pressures. In 41 consecutive patients with craniosynostosis, intracranial pressure and intracranial volume were measured. Of the 41 patients, 38 (92.6%) had raised intracranial pressure but only 4 (9.7%) had a decreased skull volume. In the present study, there is no correlation between intracranial volume and intracranial pressure. This study confirms that the measurement of intracranial volume, a non invasive procedure, cannot be used to assess intracranial pressure and to avoid an invasive procedure. PMID- 1638298 TI - The sensate deep inferior epigastric artery local musculocutaneous flap: report of a further case. PMID- 1638297 TI - The cervical tube pedicle flap: uses in facial reconstruction. AB - Most reconstructive surgeons will not commonly need to use the transverse cervical tube pedicle flap in facial reconstruction but this straightforward and simple technique can be very useful in certain instances. Some of the techniques of reconstructive surgery which have stood the test of time should not be forgotten even when the most recent reconstructive options are available. PMID- 1638299 TI - Complete bilateral cleft lip. PMID- 1638300 TI - A comparison of the use of polythene and jelonet as temporary dressing for excised wound. PMID- 1638301 TI - Venous flaps. PMID- 1638302 TI - Evaluation in mental health care. PMID- 1638303 TI - Long-term mortality in anorexia nervosa. A 20-year follow-up of the St George's and Aberdeen cohorts. AB - Two cohorts of anorexia nervosa patients were followed up for a mean of 20 years. All except 4% of each cohort was traced. The crude mortalities were: St George's, 4%; Aberdeen, 13%. The SMRs were: St George's, 136; Aberdeen, 471. If the untraced were assumed to be dead, crude mortalities were 7.6% and 15.9% respectively, and SMRs were 276 and 592 respectively. Causes of death were complications of the illness and suicide. Medical treatment may reduce early mortality, while comprehensive medical and psychotherapeutic treatment may reduce late mortality. PMID- 1638305 TI - Deliberate self-poisoning in Asian and Caucasian 12-15-year-olds. AB - The mean annual rates of hospital admission for deliberate self-poisoning were calculated for Caucasian and Asian 12-15-year-olds between 1982 and 1990 as 2.31 and 2.47 per 1000 respectively. There was an excess of girls in each group. PMID- 1638304 TI - Screening of acute psychiatric admissions for previously undiagnosed systemic lupus erythematosus. AB - An auto-antibody screen for SLE, which included antinuclear antibodies, was performed on 296 patients admitted to acute psychiatric and psychogeriatric wards. Three cases (1% of those screened) of previously undiagnosed SLE were found, and one patient was found to have autoimmune chronic active hepatitis. An auto-antibody screen may be a useful investigation in psychiatric practice. PMID- 1638306 TI - Minaprine in depression. A controlled trial with amitriptyline. AB - Minaprine (200 mg daily, either once or divided b.d.) was compared with amitriptyline (25-50 mg t.d.s.) over six weeks in 144 patients with major depression. Significant reductions in HRSD scores at the end of six weeks' treatment were recorded with both dose regimes of minaprine and with amitriptyline, with no significant differences between them. There was a significantly greater incidence of drowsiness and dry mouth with amitriptyline than with minaprine. PMID- 1638307 TI - Depression and 'hassles' in globus pharyngis. AB - A group of 25 patients (16 women, 9 men) attending an ENT department with globus sensation and 25 matched ENT controls were assessed using the Beck Depression Inventory and scales for daily stressful events ('hassles'). Globus patients of both sexes were significantly more depressed than controls and had Beck scores suggestive of significant depression. Thirteen patients, but only two controls, had an independent life event within two months of disease onset, and patients had higher hassles scores than controls. PMID- 1638308 TI - The treatment of a chronic organic mental disorder with dextromethorphan in a man with severe mental retardation. AB - Response to dextromethorphan (15 mg b.i.d.), an antitussive agent not usually considered to have psychotropic properties, was seen in a 25-year-old man with severe developmental disabilities, congenital rubella, and an organic mental disorder. Dextromethorphan affects CNS serotonergic systems, and this was the probable therapeutic mechanism. This and other published cases suggest the existence of a distinct organic mental syndrome in developmentally disabled persons which responds to drugs that increase indoleaminergic activity. PMID- 1638310 TI - Dementia presenting with sore eyes. AB - A patient who presented with soreness of her eyes was given a diagnosis of dementia of the frontal type (DFT) complicated by a major depressive illness. The report illustrates the multiplicity of presenting symptoms in patients with dementia. Resistance to treatment is often an indication that a depressive disorder is symptomatic of underlying organic brain disease. PMID- 1638309 TI - Psychiatric aspects of liver disease. AB - This paper reviews the literature on the effects of liver disease on mental health, a topic which has been relatively neglected in the recent psychiatric literature. It discusses both the encephalopathy which may be associated with liver disease of almost any type and the psychological consequences of specific liver disorders. Also considered are the effects of liver disease on sexual function; the relationship between alcohol and hepatic disorder in causing mental disturbance; the effects of childhood liver disease; psychiatric aspects of liver transplantation; and the use of psychotropic drugs in patients with hepatic dysfunction. PMID- 1638311 TI - Capgras and koro. PMID- 1638312 TI - Daily living programme. PMID- 1638314 TI - Schizophrenia following prenatal exposure to influenza epidemics between 1939 and 1960. PMID- 1638313 TI - Enhancement of recovery from psychiatric illness by methylfolate. PMID- 1638315 TI - Psychotherapy in non-Western cultures. PMID- 1638316 TI - Lithium augmentation in antidepressant-resistant patients. PMID- 1638317 TI - Who benefits from ECT? PMID- 1638318 TI - Acute transient stress-induced hallucinations in soldiers. PMID- 1638319 TI - Drug therapy of post-traumatic stress disorder. PMID- 1638320 TI - Child psychiatry in the 20th century. PMID- 1638321 TI - Sex differences in the familial risk of schizophrenia: data from Rudin's study. PMID- 1638323 TI - The distorting influence of time. PMID- 1638324 TI - Iron Maiden's deja vu. PMID- 1638325 TI - Currie's complaint? PMID- 1638326 TI - Psychotherapy in borderline and narcissistic personality disorder. AB - Psychodynamic concepts about borderline personality disorder are reviewed and the literature concerning psychotherapeutic treatment of this group is examined. The treatment contexts considered include: psychoanalysis and intensive (expressive) psychoanalytic psychotherapy, supportive psychotherapy, group psychotherapy, family therapy, in-patient treatment, the therapeutic community, cognitive behavioural approaches, and combinations of drugs and psychotherapy. The practical implications of recent follow-up studies for intervention strategies are considered. PMID- 1638327 TI - Psychosocial factors, arousal and schizophrenic relapse. The psychophysiological data. PMID- 1638322 TI - Amnesia in fugue states--neurological or psychogenic basis. PMID- 1638328 TI - Social factors and recovery from anxiety and depressive disorders. A test of specificity. AB - Analysis of 33 instances of recovery or improvement among 92 women with anxiety, and 49 instances of recovery and improvement among 67 episodes of depression, showed that recovery and improvement, when compared with conditions not changing, were associated with a prior positive event. Such events were characterised by one or more of three dimensions: the 'anchoring' dimension involved increased security; 'fresh-start', increased hope arising from a lessening of a difficulty or deprivation; and 'relief', the amelioration of a difficulty not involving any sense of a fresh start. Events characterised by anchoring were more often associated with recovery or improvement in anxiety, and those characterised as fresh-start were associated with recovery or improvement in depression. Recovery or improvement in both disorders was more likely to be associated with both anchoring and fresh-start events. The study involved the reworking of some social and clinical material, and although done blind should be seen as exploratory. PMID- 1638329 TI - Evidence for a pseudoautosomal locus for schizophrenia. I: A replication study using phenotype analysis. AB - A locus for schizophrenia within the pseudoautosomal region of chromosomes X and Y has been suggested by Crow on the basis of epidemiological data. The present report replicates this finding in a sample of 38 French multiply affected families with schizophrenia. Sibship and pairwise analysis, with or without weighted-pair correction, with three different systems of family classifications, showed there to be an excess of same-sex pairs in paternally derived sibships, as predicted by the pseudoautosomal hypothesis. PMID- 1638330 TI - Evidence for a pseudoautosomal locus for schizophrenia. II: Replication of a non random segregation of alleles at the DXYS14 locus. AB - Because of an association between sexual aneuploidies and schizophrenia, and because schizophrenic siblings have been found to be more often of the same than of the opposite sex, the susceptibility locus for schizophrenia is thought to lie within the pseudoautosomal region of the sex chromosomes. We analysed 33 sibships comprising 18 pairs, 13 trios, and 2 quartets of affected siblings, and found support for non-random segregation of of alleles at the DXYS14 locus in affected siblings. These findings are consistent with the pseudoautosomal hypothesis for schizophrenia and favour a genetic linkage between DXYS14 and the disease. PMID- 1638332 TI - Estimation of premorbid intelligence in schizophrenia. AB - To determine whether the National Adult Reading Test (NART) would provide a valid estimate of premorbid intelligence in schizophrenia, two schizophrenic samples were recruited, one consisting of 35 patients resident in long-stay wards, the other of 29 patients normally resident in the community. Schizophrenic patients were individually matched for age, sex, and education with a healthy, normal subject. Both schizophrenic samples scored significantly lower on the Wechsler Adult Intelligence Scale (WAIS) than their respective control groups. NART estimated IQ did not differ significantly between the community-resident schizophrenics and their controls, suggesting that the NART provides a valid means of estimating premorbid intelligence in such a population. NART-estimated IQ was significantly lower in the long-stay sample than in their controls. Although low NART scores in this latter sample could be a valid reflection of low premorbid IQ, the alternative explanation that NART performance was impaired by onset of the disease cannot be ruled out. PMID- 1638334 TI - Physical illness in chronic psychiatric patients from a community psychiatric unit revisited. A three-year follow-up study. AB - A group of 156 psychiatric patients from an urban community psychiatric unit for chronic psychiatric patients was routinely medically screened and reported on. Re evaluation of the medical diseases found in those patients was carried out three years later. Those who were still being treated--73 patients (47%)--were interviewed, as were their psychiatrist and, where necessary, their general practitioner (GP). The implementation of medical recommendations given following the physical screening by the specialist in internal medicine was also assessed. Re-evaluation of the diagnoses confirmed that 36% of this population had one or more physical diseases, rather than the 53% found earlier. The results show that the majority of physical complaints and diseases as well as functional illnesses were as persistent as the psychiatric diagnoses in this patient group. The patients' GP seems to be the person best suited as the primary physician responsible for the patient's physical health. PMID- 1638333 TI - A needs survey among patients in Leros asylum. AB - The recent exposure of the plight of inmates living in poor conditions at the state asylum on the Greek island of Leros has caused public and professional outrage. If Greece is to avoid mistakes made by other countries, the plans for rehabilitating the patients and closing the hospital should from the outset include identification of the precise needs of patients for support and care. The survey of the patients' characteristics and needs for care found that most patients had no outside friends or relatives, and most were unable to perform basic daily skills. They shared many basic characteristics, however, with a large sample of the long-stay population in the UK, and 25% were thought to be able to live independently. PMID- 1638335 TI - Disulfiram treatment of alcoholism. AB - To assess the efficacy of supervised disulfiram as an adjunct to out-patient treatment of alcoholics, a randomised, partially blind, six-month follow-up study was conducted in which 126 patients received 200 mg disulfiram or 100 mg vitamin C under the supervision of a nominated informant. In the opinion of the (blinded) independent assessor, patients on disulfiram increased average total abstinent days by 100 and patients on vitamin C by 69, thus enhancing by one-third this measure of treatment outcome. Mean weekly alcohol consumption was reduced by 162 units with disulfiram, compared with 105 units with vitamin C, and the disulfiram patients reduced their total six-month alcohol consumption by 2572 units compared with an average reduction of 1448 units in the vitamin C group. Serum gamma-GT showed a mean fall of 21 IU/I in patients on disulfiram but rose by a mean of 13 IU/I with vitamin C. Unwanted effects in the disulfiram group led to a dose reduction in seven patients and to treatment withdrawal in four (and in one vitamin C patient). Two-thirds of the disulfiram group asked to continue the treatment at the end of the study. There were no medically serious adverse reactions. PMID- 1638336 TI - Sexual abuse and the severity of bulimic symptoms. AB - In a clinical series of 40 bulimic women, a reported history of unwanted sexual experience was associated with more frequent bingeing and (to a lesser extent) vomiting. These symptoms were more marked when the abuse was intrafamilial, involved force, or occurred before the victim was 14 years old. Further research is required to establish the causal links between the phenomena of sexual abuse and bulimic symptoms. PMID- 1638338 TI - Coping with hearing voices: an emancipatory approach. AB - A questionnaire comprising 30 open-ended questions was sent to 450 people with chronic hallucinations of hearing voices who had responded to a request on television. Of the 254 replies, 186 could be used for analysis. It was doubtful whether 13 of these respondents were experiencing true hallucinations. Of the remaining 173 subjects, 115 reported an inability to cope with the voices. Ninety seven respondents were in psychiatric care, and copers were significantly less often in psychiatric care (24%) than non-copers (49%). Four coping strategies were apparent: distraction, ignoring the voices, selective listening to them, and setting limits on their influence. PMID- 1638339 TI - J-wire facilitates retrograde manipulation of ureteric calculi prior to extracorporeal shock wave lithotripsy. AB - During a 13-month period, 55 patients underwent attempted retrograde manipulation for ureteric lying above the pelvic brim. The mean stone burden was 11 mm (range 5-21); 41 stones (75%) were primary ureteric calculi and 14 (25%) were fragments resulting from extracorporeal shock wave lithotripsy to renal calculi. The method of retrograde manipulation was recorded prospectively. Retrograde flushing through an 8F angiography catheter with a mixture of saline and lignocaine gel was successful in 27 patients (49%). The insertion of a J-wire through the angiocath allowed for successful manipulation in a further 17 patients (31%). Retrograde manipulation was impossible in 11 patients (20%). There were 4 complications (7%), none attributable to the use of a J-wire. PMID- 1638337 TI - The effects of electroconvulsive therapy on plasma insulin and glucose in depression. AB - The effects of ECT on plasma insulin and glucose were assessed in 20 depressed patients, during the first, third and fifth session of ECT. After each administration of ECT there was a significant rise in blood glucose and plasma insulin levels, both of which peaked at 15 minutes. Insulin responses tended to attenuate over the course of ECT, whereas the glucose responses were similar for all three treatments. ECT was effective in all patients, although two months after the last treatment nine patients had partially relapsed (Hamilton score greater than 15). Those who relapsed had a more attenuated insulin response at the fifth treatment than those who had remained well, which suggests that insulin response to ECT may be predictive of clinical outcome. PMID- 1638342 TI - Long-term follow-up of women treated with perurethral Teflon injections for stress incontinence. AB - The perurethral injection of Teflon has been advocated as a simple, economical and effective treatment of stress incontinence in women. We have reviewed patients treated by this technique in Nottingham. Improvement in their symptoms fell from 80% immediately after operation to 27% at follow-up 3 years later. Because of the disappointing long-term results we have abandoned this procedure for the treatment of stress incontinence. PMID- 1638341 TI - Dialysis in patients with upper urinary tract transitional cell carcinoma. AB - In some patients with primary malignant disease of the kidney the only way of achieving a cure may involve radical surgery. If the tumour is bilateral or involves a solitary kidney, renal failure may be unavoidable. The role of dialysis and transplantation in these patients following "curative" cancer surgery is not clear. A review of the literature and experience with 4 patients who ultimately had bilateral nephrectomies for multiple recurrent upper tract urothelial malignancy is reported. These 4 patients remained free of tumour recurrence on dialysis at 5, 8, 12 and 72 months respectively since commencing dialysis, although 2 have died from unrelated causes. It would seem reasonable to offer dialysis followed by subsequent transplantation in this group of patients after a period of 1 to 2 years has elapsed without any evidence of malignant recurrence. PMID- 1638343 TI - Subjective and objective effects of intravaginal electrical myostimulation and biofeedback in patients with genuine stress urinary incontinence. AB - A group of 36 patients (18 premenopausal and 18 postmenopausal), all suffering from genuine stress urinary incontinence, underwent conservative treatment with 6 sessions of intravaginal electromyostimulation followed by 6 sessions of biofeedback; 89% of patients reported an improvement, 5.5% considered themselves cured and 5.5% reported no change. Intravaginal pressure measured before and after therapy increased by an average of 11 cm H2O in premenopausal patients and 17 cm H2O in the postmenopausal group. Intravaginal pressure increased in all patients and, according to maximal urethral closure pressure, this increasing intravaginal pressure was observed even in patients with low pressure urethras. The urodynamic factors studied were functional length, maximum urethral closing pressure and pressure transmission, together with urethral surface at rest and during stress, and residual surface. No significant changes were noted before and after treatment. The excellent subjective results contrast with the absence of improvement in these values. PMID- 1638331 TI - No evidence for a pseudoautosomal locus for schizophrenia. Linkage analysis of multiply affected families. AB - Evidence for a pseudoautosomal locus for a schizophrenia susceptibility gene was sought by two forms of analysis of 25 multiply affected families. Firstly, in the sample as a whole there was an excess of same-sex over mixed-sex siblings compared with that expected. Secondly, linkage analysis was performed in six of the families. The genotypes were studied for DXYS14, a highly polymorphic marker in the telomeric pseudoautosomal region. No evidence for positive linkage was found with two-point analysis under eight different genetic models for the mode of transmission. A non-parametric, sibling-pair analysis also failed to detect linkage. Our findings provide no evidence for linkage within the pseudoautosomal region; same-sex concordance must arise from some other mechanism. PMID- 1638340 TI - Thiazide treatment for calcium urolithiasis in patients with idiopathic hypercalciuria. AB - In a randomised trial based on a parallel design to determine the prophylactic effect of thiazide on stone formation, 210 calcium urolithiasis patients with idiopathic hypercalciuria were allocated either to treatment with trichlormethiazide (4 mg/day) or no treatment with only close follow-up; 35 patients were excluded for various reasons, including voluntary withdrawal. The background of the remaining 175 patients (82 in the thiazide group and 93 in the control group), including age and sex, was similar for both groups. In patients treated with thiazide there was a statistically significant fall in urinary calcium output. Statistical analyses also demonstrated that the stone formation rate in the thiazide group was significantly less than that in the control group. Adverse clinical reactions probably due to the drug were observed in 9 patients. These findings indicate that trichlormethiazide has a prophylactic effect on calcium urolithiasis in patients with idiopathic hypercalciuria. PMID- 1638344 TI - Reconstruction of the lower urinary tract for neurogenic bladder: lessons from the adolescent age group. AB - Of 42 adolescents with neurogenic bladder who presented for lower urinary tract reconstruction, 4 patients with severe spina bifida were unfit for major surgery. Five patients had a simple undiversion; 4 of these had a poor outcome because of unpredicted sphincter incontinence (1 patient) or instability (3). A total of 26 patients had an enterocystoplasty. All 7 patients who had a substitution cystoplasty had a good result, as did 3 males with a clam cystoplasty. Nine of 16 females had a poor result from a clam procedure. In 3 the problem lay with self catheterisation difficulties. One each had persistent hyper-reflexia and sphincter incontinence. Four had hyper-reflexia on sexual intercourse. Overall, 42% of females had problems from the retained bladder segment. Seven patients had continent urinary diversions. The results were good, although 2 Kock nipples required revision. Surgery was well tolerated. There was a 21% re-operation rate for complications. Pre-operative investigation correctly predicted sphincter competence and the need for self-catheterisation in 79 and 86% respectively. PMID- 1638346 TI - Long-term results of one-stage scrotal patch urethroplasty. AB - Of 211 patients with urethral strictures undergoing one-stage dartos pedicled island patch urethroplasty between 1970 and 1987, 194 have been followed up from 3 to 20 years. There was 1 post-operative death (from hepatitis). During the period of follow-up, strictures recurred in 14 patients (7%), some of them as late as 15 years after an apparently successful urethroplasty. Calculi forming on hairs required treatment in 6 patients (3%) and it was necessary to revise a redundant skin pouch in 6. PMID- 1638347 TI - Pre-operative assessment of Peyronie's disease using colour Doppler sonography. AB - Colour Doppler ultrasonography was used to assess 39 patients with Peyronie's disease with a suspected organic cause for their impotence. In 20 patients who complained of a uniform loss of erection, the impotence was likely to be functional in origin (90%) or occasionally venogenic (10%), the penile arterial blood flow being normal. However, patients who complained of distal flaccidity were likely to have an organic cause for their impotence (68%). This was due to proximal arterial disease (10%), plaque involvement of the distal vessels (37%), veno-occlusive dysfunction (5%) or to the soft glans syndrome (16%). PMID- 1638348 TI - Contralateral testicular blood flow in unilateral testicular torsion measured by the 133Xe clearance technique. AB - Contralateral testicular blood flow was measured by the intratesticular injection of 133Xe in 9 controls (Group 1) and in 34 adult male albino rats with experimentally induced left testicular torsion. In Group 2 (n = 9) testicular torsion was maintained for 3 h; in Group 3 (n = 7) torsion was maintained for 9 h and in Group 4 (n = 10) for 15 days. In Group 5 (n = 16) torsion was maintained for 9 h in 8 rats and the sera were given to 8 normal animals. In Groups 3, 4 and 5 there was a significant increase in contralateral testicular blood flow on the fifteenth day. This increase may be the cause of contralateral testicular damage in prolonged unilateral testicular torsion. PMID- 1638349 TI - Complete resolution of a large seminal vesicle cyst--evidence for an obstructive aetiology. AB - Seminal vesicle cysts may arise from inflammation or obstruction of the seminal vesicle or from embryological remnants such as the mullerian duct. Surgical removal has been proposed as the treatment of choice. A 19-year-old boy presented with abdominal pain and constipation. Investigations revealed a 14-cm multiloculated cyst arising from the right seminal vesicle and a small stone lodged at the orifice of the ipsilateral ejaculatory duct. Following endoscopic removal of the stone the mass decreased in size considerably and 2 months later transrectal ultrasound and magnetic resonance imaging showed normal seminal vesicles and no evidence of the cyst. This case strongly supports an obstructive aetiology for this cyst and we would suggest that, in similar cases, full assessment of the ejaculatory apparatus should be carried out to exclude an obstructive cause before embarking on major surgery. PMID- 1638350 TI - Survey of mycobacteria isolated from urine and the genitourinary tract in south east England from 1980 to 1989. AB - Between 1980 and 1989, the Public Health Laboratory Service Regional Tuberculosis Centre, Dulwich, received cultures of mycobacteria isolated from urine and the genitourinary tract of 1392 new patients: 803 isolates were members of the tuberculosis complex (753 M. tuberculosis, 45 M. bovis, 4 M. africanum) and 589 were various species of environmental mycobacteria. The incidence of the latter isolations varied by region and by year and, with 17 exceptions (13 from endometrial curettings, 2 from hydrocele fluid, 1 from a scrotal abscess and 1 from a kidney), all isolations of environmental mycobacteria were from urine; very few of them appeared to be clinically significant. Those that could be significant included 1 isolate from a kidney, 1 from a post-renal transplant patient and 4 from patients with AIDS, 3 of whom had disseminated mycobacterial disease. Reports of clinically significant isolations of environmental mycobacteria from the genitourinary tract are reviewed. PMID- 1638352 TI - The development of synthetic polymers that resist encrustation on exposure to urine. AB - The consequences of long-term exposure of synthetic materials to urine have prevented the development of alloplastic replacement of diseased or damaged parts of the urinary tract. Similarly, urethral and ureteric catheters require regular replacement if the complications of encrustation and blockage are to be avoided. The mechanism of encrustation is not understood completely and thus it is unclear why certain materials appear better able to resist encrustation. This study has involved the development of a new encrustation model to provide a reproducible and quantitative assessment of the susceptibility of polymers to encrustation. This model will allow beneficial characteristics of co-polymer design to be recognised, with the aim of finding new materials that are tolerant of exposure to urine. Results of co-polymers examined show that the incorporation of fluorine containing components confers significant resistance to the formation of encrustation. It is suggested that the physico-chemical properties of polymer surfaces may be important determinants of resistance to encrustation. PMID- 1638353 TI - Inferior vena cava obstruction secondary to urinary retention in a neonate. PMID- 1638351 TI - Potential use of tissue adhesive in urinary tract surgery. AB - The search for a tissue adhesive which obviates the need for suture materials in the apposition of wound edges is not new. The early adhesive products lacked the required safety and efficacy. Experimental use of a new fibrin adhesive has shown that it may have potential use where inflammatory reaction to the suture material is undesirable or water-tight sealing of the anastomosis is required. PMID- 1638355 TI - Metastatic malignant melanoma of the epididymis. PMID- 1638354 TI - Development of Leydig cell tumour in association with clomiphene treatment for oligozoospermia. PMID- 1638356 TI - Hypereosinophilia, cardiomyopathy and transitional cell carcinoma of the bladder. PMID- 1638345 TI - Total substitution of the lower urinary tract. A technique for either reconstruction or continent diversion. AB - A technique is described in which the right side of the colon is used for substitution cystourethroplasty, based on the flap valve principle, in order to produce a continent catheterisable outflow. The technique can equally well be used for continent diversion. PMID- 1638357 TI - Iontophoretic local anaesthesia for bladder dilatation in the treatment of interstitial cystitis. PMID- 1638358 TI - Metastatic melanoma to the testis simulating primary seminoma. PMID- 1638359 TI - Diagnosis of urinary leak in a critically ill patient using bedside 99mTc-DTPA renal scanning. PMID- 1638360 TI - Re: Gastrocystoplasty in children. Evelyn H. Dykes and P. G. Ransley. Br. J. Urol., 69, 91-95, 1992. PMID- 1638361 TI - Re: The persistent indwelling catheter. S. K. Iyer. Br. J. Urol., 69, 100, 1992. PMID- 1638362 TI - Re: Partial extraction of Double-J stent during nephrostomy tube removal and its prevention. S. Gepi-Attee et al. Br. J. Urol., 68, 552-553, 1991. PMID- 1638364 TI - Pontine pathology and voiding dysfunction. PMID- 1638363 TI - Re: Gluteal device for penile injection. A. M. Helmy. Br. J. Urol., 68, 400-403, 1991. PMID- 1638365 TI - Metastatic carcinoid tumour involving the prostate. PMID- 1638366 TI - Use of the lachrymal duct probe in epididymal aspiration. PMID- 1638367 TI - Effect of vaginal ultrasound probe on lower urinary tract function. AB - Vaginal ultrasonography has been advocated as an alternative to videocystourethrography. Ultrasound avoids the potential risks of X-rays and reduces the cost of equipment. We have investigated the effect of the vaginal probe on the physiology of the bladder and urethra. A series of 24 women underwent urethral pressure profilometry, with and without a vaginal probe in situ. There was a significant increase in maximum urethral pressure, functional urethral length and area under the profile curve both at rest and during stress in the presence of the device. This was due to stretching and compression of the urethra by the probe. Transmission pressure ratios were significantly increased for the first 3 quartiles of the urethra. Twenty women underwent lateral bead chain urethrocystography with and without a vaginal probe. At rest, the probe resulted in elevation of the bladder neck and apposition to the symphysis pubis, and during a Valsalva manoeuvre the descent of the bladder neck was restricted by the presence of the probe. These results indicate that a vaginal probe alters the position and function of the lower urinary tract. We postulate that incontinence is reduced as a result of the probe. The use of vaginal ultrasonography in the assessment of women with urinary incontinence is therefore not recommended. PMID- 1638369 TI - Electromyographic abnormalities in the urethral and anal sphincters of women with idiopathic retention of urine. AB - Previous concentric needle studies of the urethral sphincter in women with idiopathic urinary retention have found evidence of denervation and reinnervation as well as abnormal patterns of muscle fibre discharge--complex repetitive discharges (CRDs). In order to test the hypothesis that these abnormalities represented a more widespread disease process of pelvic floor function, we carried out an electromyographic (EMG) study of both anal and urethral sphincters in 18 women with idiopathic urinary retention. The urethral sphincter EMG was abnormal in 15 patients. These abnormalities included polyphasic and long duration potentials. Complex repetitive discharges were identified in 8 women. However, abnormalities of the anal sphincter were found in 14 of the 15 patients with abnormal urethral sphincter EMGs, polyphasic and abnormally long duration potentials being found in the anal sphincters of all 14 patients. In addition, 7 of the 8 women who had complex repetitive discharges in the urethral sphincters had similar complex repetitive discharges in their anal sphincters. Women with complex repetitive discharges had a significantly greater proportion of abnormal potentials than women with no such repetitive discharges. These results support the previous findings of electromyographic urethral sphincter abnormalities in women with idiopathic urinary retention, but also suggest that these abnormalities reflect a widespread disease process involving the pelvic floor in such patients. PMID- 1638368 TI - Detrusor mast cells in refractory idiopathic instability. AB - The diagnosis of interstitial cystitis (IC) is not usually considered in patients with idiopathic instability. Because histamine provokes detrusor contractions in vitro, we assessed detrusor mast cell counts in 29 females with refractory instability. Raised mast cell counts (greater than 28/mm2 of detrusor muscle, consistent with a histological diagnosis of IC) were found in 29% of such cases. Thus cystoscopy and bladder biopsy should be considered in patients with idiopathic instability which fails to respond to anticholinergic drugs, as alternative therapy may be useful. Patients with refractory instability and normal detrusor mast cell counts often gave a history of prolonged childhood nocturnal enuresis (55% of cases); in contrast, patients with intractable instability and abnormally high mast cell counts seldom gave such a history (12%). These trends may give some insight into the aetiology of idiopathic instability--"congenital" or acquired? PMID- 1638370 TI - Continent urinary diversion using an artificial urinary sphincter. AB - We report a new and simplified method of continent urinary diversion employing a modified AMS 800 artificial urinary sphincter (AUS). Our aim in using this artificial valve is to make a stoma continent, while allowing intermittent catheterisation. The AMS 800 pump is replaced by a subcutaneous injection port. This allows, by direct puncture, the accurate setting of the closing pressure by varying the volume of the intra-prosthetic liquid, with subsequent adjustment of this pressure as necessary. The cuff is placed on the subcutaneous part of the intestinal loop diversion. The pressure-regulating balloon is implanted within the area of abdominal pressure, retroperitoneally. After first confirming the efficacy of the system in 3 dogs, the device was placed in 2 patients. The first had a neuropathic bladder treated initially by enterocystoplasty with an appendicocutaneous stoma. Secondary leakage was subsequently controlled by placement of the device, with continuing excellent results at 32 months. The second patient was a girl in whom a urogenital rhabdomyosarcoma had been treated by anterior exenteration, radiotherapy and a sigmoid conduit diversion. This was subsequently converted to a continent reservoir by simple augmentation of the conduit and placement of the device, with a good result being maintained after a follow-up of 20 months. These two cases illustrate the best indications for this procedure, namely primary or secondary leakage from a supposedly continent urinary diversion, and conversion of a freely draining conduit into a continent reservoir. Although long-term results are still pending, our experience thus far encourages us to recommend this technique as a simple means of achieving a continent urinary diversion. PMID- 1638371 TI - The effect of ranitidine on urine mucus concentration in patients with enterocystoplasty. AB - We describe the effect of ranitidine in reducing mucus in urine in 8 patients with enterocystoplasty and present a simple technique for measuring the concentration of mucus in urine. After a 10-day course of ranitidine (300 mg daily in divided doses) the concentration of mucus had fallen significantly from an initial level of 1.38 +/- 0.18 to 0.39 +/- 0.04 mg/ml. PMID- 1638374 TI - Bladder cancer mortality in The Netherlands, 1955-1988. AB - In 1955, 234 men and 116 women died from bladder cancer in the Netherlands. In 1988 the numbers were 794 and 317 respectively. After adjusting for the ageing of the Dutch population since 1955, female mortality rates per 10(5) person-years appear to be very stable: 2.9 from 1955 to 1959 and 3.0 from 1985 to 1988. By contrast, an increasing trend exists in males. From 1955 to 1959 and from 1985 to 1988, bladder cancer mortality rates per 10(5) person-years were 7.5 and 12.4 respectively. For men in particular, increasing mortality (and incidence) rates are seen all over the world. In many cases this increasing trend is thought to originate from a higher risk of dying from bladder cancer in successive birth cohorts rather than from a higher risk in successive calendar periods. This so called cohort effect is explained by changes in smoking behaviour in the male population. Statistical modelling of bladder cancer mortality data from 1955 to 1988 in the Netherlands shows that the increasing temporal trend in men can also be described as a cohort effect. The risk of dying from bladder cancer increases from the 1875 birth cohort to the 1910 birth cohort, but decreases thereafter. It is concluded that this decreasing risk for generations born after 1910 will probably result in a decreasing trend in mortality in the near future, when more and more of these "youngsters" reach the age of 70+. PMID- 1638372 TI - Male and female sexual function and activity following ileal conduit urinary diversion. AB - A group of 66 patients (40 males, 26 females) underwent an ileal conduit urinary diversion because of bladder cancer (44 patients) or incontinence/bladder dysfunction (22). They were questioned about pre- and post-operative sexual function and activity and it was found that 90% of the males (26/29) who were sexually active before surgery lost the ability to achieve erection following radical cystectomy. Although they were unable to achieve penile erection, 41% were able to experience orgasm by means of masturbation. Five of the 29 males received penile implants. Five of the 6 females treated by cystectomy, who were sexually active before the operation, reported either a decrease or cessation of sexual activity (i.e. coitus) post-operatively. The main problems were a decrease in sexual desire, dyspareunia and vaginal dryness. One women reported the inability to experience orgasm after surgery. Compared with women with bladder cancer, those with incontinence/bladder dysfunction were more likely to have an active sexual life after urostomy surgery. Seven females in this group, of whom 4 were sexually inactive before surgery, increased their sexual activity after the operation. For these women the conduit operation removed the need to use incontinence pads or indwelling catheters. PMID- 1638373 TI - Cystoprostatectomy and substitution cystoplasty for locally invasive bladder cancer. AB - The results and long-term follow-up of 48 patients undergoing cystoprostatectomy and substitution cystoplasty for T2/3, M0 transitional cell carcinoma of the bladder are reported. There was no operative mortality but 1 early death from thromboembolic disease. Thirty-six patients are alive with a mean follow-up of 57 months (range 12-120). Eleven patients died of disseminated disease. Thirty-one patients (64%) regained normal continence by day and night and a further 8 were dry by day but incontinent at night; 9 patients underwent further surgery for incontinence and this was successful in 8, giving an overall continence rate of 79% and a day-time continence rate of 98%. Of the 38 patients claiming to be potent pre-operatively, 24 (63%) were potent post-operatively. Nerve-sparing cystoprostatectomy and substitution cystoplasty is a safe alternative to a "standard" cystectomy and ileal conduit diversion in a selected group of men undergoing radical surgery for invasive bladder cancer and it achieves its aims of preserving continence and potency in the majority of patients. PMID- 1638375 TI - Selective renal tumour biopsy under ultrasonic guidance. AB - Selective renal biopsy under ultrasonic guidance has been used widely because it provides safe and accurate tissue sampling. Using this technique, we biopsied 36 renal tumours and obtained specimens in 35 cases. Histology of the biopsy coincided with that of the surgical specimen in 18/21 cases. Dissemination of tumour cells, thought to have been caused by needle biopsy and/or surgical manipulation, was observed in only 1 case of sarcoma. The method thus proved effective in determining treatment and it is suggested that it should be used in accordance with the criteria which we have devised. PMID- 1638376 TI - Long-term results of treatment of urethral injuries in males caused by external trauma. AB - Of 134 males with traumatic rupture of the urethra seen between 1967 and 1989, 10 have been lost to follow-up and 124 have been followed up for 1 to 22 years (mean 8); 100 patients had a pelvic fracture (3 with associated rectal injury) and 24 had perineal injuries. Prior to referral 31 patients (25%) had undergone treatment in addition to suprapubic cystostomy. Wherever possible, strictures were managed by optical urethrotomy (33) or intermittent dilatation (4). In 2 patients only a suprapubic cystostomy was possible. Skin inlay urethroplasty in 1 or 2 stages was performed in 75 cases, an end-to-end anastomosis with or without resection of the symphysis pubis in 7 and a scrotal tube pull-through in 3. The immediate and long-term results depended on the severity of the original injury. With minimal displacement the management was simple and the long-term prognosis good, a single urethrotomy being sufficient in 22 patients. Where there was considerable displacement the initial management was more difficult and there was a high incidence of long-term complications: of 73 patients treated by urethroplasty or end-to-end anastomosis, significant post-operative infection occurred in 11 (15%) and restenosis in 15 (20%), of whom 7 required a revision urethroplasty. Data in respect of potency were recorded in 80 patients: 28 of these were impotent, 20 of the 28 having sustained an injury with considerable displacement. PMID- 1638379 TI - Vacuum constriction devices: second-line conservative treatment for impotence. AB - Intracavernosal pharmacotherapy is not a universally successful treatment of impotence. Vacuum constriction devices are reported to be an effective non operative alternative. This study investigated the value of these devices in 45 impotent men who had failed to become established on intracavernosal papaverine. Although 38 were able to obtain an erection-like state using a vacuum constriction device, only 12 were able to enjoy satisfactory sexual intercourse and, of these, just 7 men found them of sufficient benefit to warrant purchase. Success is not predicted by aetiology. Vacuum constriction devices are of some use, but a trial period of use should be allowed to each patient before purchase. PMID- 1638378 TI - New approach to the management of Fournier's gangrene. AB - A new method of treating Fournier's gangrene is described in 13 patients. There was no mortality and the average hospital stay was 10 days. Considerable gain in man-hours and expense was recorded when compared with the old method of treatment with antibiotics and wound debridement. PMID- 1638377 TI - Treatment of hydrocele: randomised prospective study of simple aspiration and sclerotherapy with tetracycline. AB - Following reports in the literature on the efficacy of tetracycline sclerotherapy in the treatment of hydroceles, we carried out a randomised prospective study of 45 patients (50 hydroceles), comparing simple evacuation with tetracycline sclerotherapy. The results revealed no statistically significant difference in the percentage of success between the 2 groups, but complications were more common in the patients treated with tetracycline. The good results reported by other authors in non-randomised studies are, therefore, not confirmed. PMID- 1638380 TI - Occupational urothelial cancer in a former iron foundry worker. PMID- 1638382 TI - Verrucous carcinoma of the bladder. PMID- 1638381 TI - Malignant hypertension due to embolisation of a clear cell renal carcinoma. PMID- 1638384 TI - Columnar metaplasia complicating neurogenic bladder in a child. PMID- 1638383 TI - Late metastasis from ovarian tumour. An unusual cause of hydronephrosis. PMID- 1638385 TI - Syphilis of the ureter. PMID- 1638386 TI - Photoreceptor differentiation in retinal xenografts of fetal monkey retina. AB - Although the potential of retinal grafts to provide the host eye with rod cells is presently well established, the possibility of grafting cone photoreceptors has not been documented. In this study, the neural retinas of two Cebus apella monkey fetuses were xenografted into immunosuppressed Fischer 344 adult rats. Histological analysis showed intimate apposition between the grafted donor cells and the neighboring host rat retina. The transplanted cells survived well and often overgrew the boundaries of the host retina, expanding into the host vitreous cavity. These cells formed histogenetically differentiated structures predominantly populated by the photoreceptors. When transplanted into a foreign environment, donor cells formed inner segments which exhibited the basic morphology of cells developed in situ. This study demonstrates that embryonic monkey neural retina is a viable source of xenograft material. It also indicates that an advanced embryonic stage is not a deterrent to survival and differentiation of grafted primate neuroretinal cells. The successful transplantation of these cells, especially under the relatively adverse conditions of a xenograft, raises the hope that retinal transplantation may in fact be a useful technique for repairing both rod and cone function in damaged retinas of higher animals including humans. PMID- 1638388 TI - Repetitive transient forebrain ischemia in gerbils: delayed neuronal damage in the substantia nigra reticulata. AB - Repetitive cerebral ischemia results in severe neuronal damage in multiple regions of the brain including the hippocampus, striatum, thalamus, medial geniculate nucleus and the substantia nigra reticulata (SNr). We postulated that the damage in the SNr was delayed, resulting from a loss of striatal inhibitory input. We used the gerbil model of repetitive ischemia (3 min times 2 and 3 min times 3) to evaluate the extent of neuronal damage at 2, 3, 5 and 7 days after the ischemic insult. Silver degeneration stain was used for histological evaluation. Our results indicate that damage in the SNr begins after 48 h and is maximum at 7 days. This delay in onset of damage offers a window for pharmacological protection. PMID- 1638387 TI - Ultrastructural concomitants of anoxic injury and early post-anoxic recovery in rat optic nerve. AB - To study the effects of anoxia on CNS white matter, we examined the ultrastructure of axons and glial cells in a white matter tract, the rat optic nerve, that was subjected to a standardized anoxic insult in vitro. Previous electrophysiological studies showed that in this model, action potential conduction is rapidly abolished by anoxia, and conduction is restored after reoxygenation in about 30% of axons following a 60-min anoxic period. The present study examined the ultrastructural correlates of anoxic injury and early post anoxic recovery in this model. Optic nerves examined immediately following 60 min of anoxia displayed numerous large, apparently empty zones located within myelin sheaths adjacent to the axon. The myelin remained compact and retained its periodicity. In some regions, the extracellular space was enlarged. There was mitochondrial swelling with loss of normal cristae. There was also loss of microtubules and, to a smaller degree, of neurofilaments in large-diameter axons. Some nodes of Ranvier in anoxic optic nerves displayed detachment of terminal oligodendroglial loops or retraction of the myelin from the node; the presence of tongue-like processes, extending from nearby cells under the detached myelin loops, suggested a possible role of cell-mediated damage to the paranodal myelin. Bundles of dense astrocyte processes were present, and there was vesicular degeneration of perinodal astrocyte processes. In optic nerves that had been permitted to recover for 60 min in oxygenated Ringers following the anoxic period, empty zones were only rarely observed within myelin sheaths and, when present, were smaller than in optic nerves immediately following 60 min of anoxia. The axoplasm of large fibers continued to show loss of microtubules and neurofilaments, as well as mitochondrial swelling. Myelin appeared normal, and only rare paranodal oligodendroglial processes remained unattached from the axon membrane. These results provide support for the idea that, during anoxia, myelinated axons are damaged with significant injury to cytoskeletal elements, probably due to an influx of calcium. The ultrastructural results, together with our earlier observations on the physiological correlates of anoxia and re oxygenation, suggest that the development of intramyelinic spaces or damage to paranodes lead to conduction block in the anoxic optic nerve. These results also suggest that repair of these structural abnormalities may provide a morphological basis for the early recovery of conduction that occurs after re-oxygenation. PMID- 1638390 TI - Excitatory inputs to layer V pyramidal cells of rat primary visual cortex revealed by acetylcholine activation. AB - Cells in layers II-III or VI were activated by microdrop application of acetylcholine (ACh), while monitoring the intracellular response of layer V pyramidal cells. This enabled the tracing of functional connections between the cells of layers II-III or VI with those of layer V. ACh activation of layer II III or VI cells resulted in a small depolarization of these cells, accompanied by a burst of excitatory postsynaptic potentials (EPSPs) from layer V pyramidal cells. These effects of ACh were blocked by tetrodotoxin (TTX), suggesting the involvement of action potentials in their production. The input resistance of layer V pyramidal cells during and after the EPSP burst was not significantly different from control values, further suggesting an indirect effect of ACh on layer V pyramidal cells. Isolation of the supragranular layer, by horizontal cutting, did not prevent the EPSP burst evoked by ACh application to the lower layer VI, suggesting a direct input from layer VI to layer V pyramidal cells. ACh applied near pyramidal cells in layers II-III, V or VI caused transient hyperpolarization associated with a decrease in input resistance followed by a large depolarization, an increase in input resistance, and action potential discharges. The ACh-mediated hyperpolarization and the train of action potentials of layer II-III pyramidal cells were blocked by TTX. Thus the ACh-activated cells in layers II-III and VI make an excitatory synaptic contact with layer V pyramidal cells, producing the EPSP burst observed in layer V. PMID- 1638389 TI - Dissociation between in vivo hippocampal norepinephrine response and behavioral/neuroendocrine responses to noise stress in rats. AB - The behavioral and extracellular hippocampal norepinephrine responses to audiogenic stress were concomitantly characterized in freely moving rats using in vivo microdialysis. Noise stimulation produced a rapid, but short-lived increase in norepinephrine release from the hippocampus during the first 20 min of noise presentation that declined to baseline levels for the duration of the noise stimulation and following noise offset. In contrast, the behavioral response persisted throughout the duration of the noise stimulation. In a separate group of similarly treated animals, neuroendocrine indices of stress were monitored during exposure to noise. Consistent with the behavioral response, corticosterone and adrenocorticotropic hormone remained elevated for the duration of noise presentation. These findings support a dissociation between the hippocampal norepinephrine response and the behavioral and neuroendocrine response patterns and suggest that other systems may be involved in the regulation of behavioral responsiveness to aversive stimuli. PMID- 1638391 TI - Differential effect of self-stimulation on dopamine release and metabolism in the rat medial frontal cortex, nucleus accumbens and striatum studied by in vivo microdialysis. AB - Changes in the extracellular levels of dopamine (DA) and its metabolites in the dopaminergic terminal regions, the medial frontal cortex (MFC), nucleus accumbens (NAC), and striatum (STR), were measured by microdialysis during self-stimulation of the medial forebrain bundle (MFB) in rats pretreated with the DA uptake inhibitor, nomifensine (1 mg/kg, i.p.). Self-stimulation of the MFB in nomifensine-pretreated rats caused an increase in the extracellular DA level in the MFC and NAC but not in the STR. Self-stimulation also increased the extracellular concentrations of the main DA metabolites, 3,4 dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) to a similar extent in the MFC and NAC and to a lesser extent in the STR. Thus, there was a regional difference in the neurochemical changes following self-stimulation with either the MFC or the NAC showing larger extracellular levels of DA, DOPAC, and HVA than the STR. Furthermore, these changes were observed on both hemispheres ipsilateral and contralateral to the stimulation. The results indicate that self stimulation of the MFB preferentially activates the mesocorticolimbic DA systems, thereby bilateral increases in the release of DA and its metabolism being produced in their terminal regions, the MFC and NAC. PMID- 1638392 TI - Conduction properties of central nerve fibers remyelinated by Schwann cells. AB - Demyelination of central axons arises from a number of conditions, including multiple sclerosis and spinal cord compression. The demyelination disrupts conduction and leads directly to the production of symptoms. Repair of the demyelination by peripheral myelinating cells could potentially relieve the symptoms, but the conduction properties of central axons remyelinated by Schwann cells have yet to be studied in detail. This paper examined the conduction properties of such axons. Large focal demyelinating and remyelinating lesions were induced in the dorsal columns of rats by the intraspinal injection of ethidium bromide. Recordings of compound action potentials conducted through these lesions were then made at various recovery times. Thus the changing conduction properties of the affected fibers could be correlated with the different stages of lesion development. During the early stages of demyelination there was widespread conduction block, with no evidence of appreciable conduction occurring with prolonged latency or refractory period of transmission (RPT). However, with the onset of remyelination by Schwann cells, conduction was restored in many axons, and most, if not all, of the affected axons eventually showed successful conduction through the lesion. Initially the conduction was characterized by very prolonged latency, long RPT, and an inability to conduct fast trains of impulses. These deficits became less prominent as remyelination progressed. In chronically remyelinated axons the RPT was restored to within normal limits, although some deficit in both conduction velocity and the ability to conduct trains of impulses persisted. Since these deficits were not severe we conclude that remyelination of central demyelinated axons by Schwann cells should be effective in promoting the restoration of normal function. PMID- 1638394 TI - Signal shaping by voltage-gated currents in retinal ganglion cells. AB - The role of voltage-gated currents in information processing by retinal ganglion cells was assessed by comparing the light-evoked current and voltage responses of identified ganglion cells with those produced by current injection. These experiments show that the light-evoked signal is clipped at the bipolar-to ganglion cell synapse because the synaptic current evoked by illumination with bright light is greater than that which the cell can convert into a change in action potential frequency. Ganglion cell responses to injected current fell into 2 classes: those producing sustained spiking responses and those producing transient responses. Further, this division is correlated with the light response of the cells; those producing transient responses to exogenous current produced transient responses to light, while those with sustained responses to current injection produced sustained responses to light flashes. The voltage-gated currents present in the ganglion cell membrane contribute to information processing in the retina by clipping the light-evoked signal and by producing transcience in the output of the retina. PMID- 1638393 TI - Gender differences in correlations of cerebral glucose metabolic rates in young normal adults. AB - Correlational analysis of normalized regional cerebral metabolic data obtained by positron emission tomography, in healthy subjects in the 'resting' state (eyes covered, ears plugged) using [18F]2-fluoro-2-deoxy-D-glucose, demonstrated gender differences in patterns of functional associations. Fifteen women and 18 men (less than 40 yr) were scanned with a Scanditronix PC1024-7B tomograph. The brain was divided into 65 regions of interest (ROIs). There were no differences between men and women in global or regional metabolic rates, or in metabolic right-left asymmetries. Although the total number of significant correlations did not differ between men and women, patterns differed: female correlations rF were most positive than male correlations rM more often than rM greater than rF; and most rF greater than rM cases involved left frontal and sensorimotor ROIs, whereas most rM greater than rF cases involved right sensorimotor and occipital ROIs. The findings demonstrate gender differences in the pattern of functional neocortical interactions at the 'resting' state. PMID- 1638395 TI - Quantitation of ventricular size in normal and spontaneously hypertensive rats by magnetic resonance imaging. AB - Magnetic resonance imaging (MRI) performed at high field (4.7 Tesla), and high spatial resolution (0.6 mm slice thickness, 0.18 mm inplane) enabled noninvasive quantitative measurement of the ventricular vol. in live rats. Comparing the results for 15 male Wistar-Kyoto (WKY) rats, aged 2.5-10 months, with those from 17 spontaneously hypertensive rats (SHR), clearly confirmed the previously reported elevated ventricular vols. in the SHR strain. A significant difference in ventricular vol. between the two strains was detected above the age of 3 months. For mature animals above the age of 6 months the mean vol. in the SHR strain was elevated by about a factor of two compared to the WKY control animals. PMID- 1638396 TI - Stimulation of substantia nigra pars reticulata suppresses neocortical seizures. AB - The effects of unilateral electrical stimulation of the substantia nigra pars reticulata (SNpr) on the electrocorticographic (ECoG) manifestations of seizures were studied in anesthetized rats. Epileptiform activity was provoked in the primary focus (Pf) by unilateral, local application of 3-aminopyridine which induced secondary focus in the homologous area of the contralateral cortex (mirror focus, Mf). The position of the electrode for stimulation of SNpr was contralateral to the Pf. The results showed a strong suppressive nigral effect on cortical seizure propagation and on seizure susceptibility in both hemispheres. Stimulation of the SNpr prevented the manifestation of sustained epileptiform events, decreased the rate of seizure appearance in the Mf, delayed the onset of paroxysmal activity and markedly reduced the amplitude and duration of ictal episodes at both foci. Seizure potentials of lower frequencies disappeared, while the relative proportion of those of higher frequency increased in SNpr-stimulated animals. SNpr stimulation had no significant effect on fully developed seizures. Our observations support the idea that SNpr might be involved in the control of cortical seizure susceptibility, regulating other structures which are possibly involved in the generation and propagation of seizure. PMID- 1638397 TI - L1 immunoreactivity in the developing fish visual system. AB - Previous studies have suggested that L1, the cell adhesion molecule, is present in the regenerating fish optic nerve. The present study was undertaken in order to determine whether L1 is expressed by fish neurons and specifically by non myelinated axons, using fish retinal explants in vitro and the developing fish visual system in vivo. In vitro, the nonmyelinated axons emerging from retinal explants showed L1 immunoreactivity and in vivo, L1 immunoreactive sites were found to be associated with areas rich in non-myelinated axons. At embryonic stage 23, as the eye developed and optic nerve axons began to elongate towards the tectum, L1-like immunoreactivity was seen both in optic nerve and in plexiform layers of the retina. At this stage and until hatching, the cellular layers within the retina showed little or no staining relative to the layers containing axons or dendrites. After hatching, L1 immunoreactivity was also observed in the ganglion cell layer, but upon maturation both the retina and the optic nerve lost most of their L1 immunoreactivity. We therefore suggest that non myelinated axons of the fish visual system express L1 during development, which is lost after myelination and presumably reappears during regeneration. PMID- 1638399 TI - Characterization of a neurotrophic factor produced by cultured astrocytes involved in the regulation of subcortical cholinergic neurons. AB - When dissociated subcortical cells were cultured in the presence of conditioned medium of relatively differentiated astrocytes (ACM), a marked increase was observed in the expression of choline acetyltransferase (ChAT), an enzyme required for the synthesis of the neurotransmitter acetylcholine. Astrocytes from the target regions of subcortical neurons, the hippocampus and the cerebral cortex, produced neurotrophic factor consistently more than those derived from the nontarget region, the cerebellum. The production of cholinergic trophic activity was increased with the maturation of astrocytes. Even though, nerve growth factor (NGF) and ciliary neurotrophic factor (CNTF) are known cholinergic trophic compounds produced by astrocytes in vitro, a large part of the neurotrophic activity in our ACM was not related to either of these 2 factors. This is because (i) ACM and NGF produced an additive effect on ChAT activity, (ii) only a small proportion of the cholinergic trophic activity in ACM was abolished by anti-NGF antibody, and (iii) treatment with CNTF had no effect on ChAT activity of basal forebrain cholinergic neurons. On the other hand, when cholinergic neurons are cultured on a preformed layer of astrocytes, addition of basal fibroblast growth factor (bFGF) failed to increase further the ChAT activity. Similarly the effects of ACM and bFGF were not additive. A large proportion of the cholinergic trophic activity in ACM was neutralized by anti bFGF antibody. These findings would suggest that the trophic activity on septal cholinergic neurons in our ACM was due to bFGF or a bFGF-like compound. PMID- 1638398 TI - Differential inhibition by NMDA antagonists of rapid tolerance to, and cross tolerance between, ethanol and chlordiazepoxide. AB - We have recently found that the non-competitive N-methyl-D-aspartate (NMDA) antagonists, (+)MK-801 and ketamine, block the development of rapid tolerance to ethanol. In the present report we show that they also block rapid cross-tolerance from chlordiazepoxide to ethanol as well as ethanol to chlordiazepoxide. However, NMDA antagonists fail to block the development of rapid tolerance to chlordiazepoxide. Our results suggest that NMDA antagonists may affect not only the acquisition of rapid tolerance or cross-tolerance to sedatives but also the ability to express that tolerance or cross-tolerance, depending on the drugs used. It is also possible that the phenomena of rapid tolerance and rapid cross tolerance have basic differences not previously reported in the literature. PMID- 1638400 TI - 5-Hydroxytryptamine stimulates corticosteroid-sensitive CRF release from cultured foetal hypothalamic cells. Role of protein kinases. AB - 5-Hydroxytryptamine (5-HT) has been shown to activate the hypothalamo-pituitary adrenal axis, possibly by a direct action on hypothalamic CRF synthesis and release. In order to study the mechanisms involved in this effect, foetal hypothalamic cells were cultured and corticotropin-releasing factor-41 (CRF) release was measured by radioimmunoassay. 5-HT induced CRF release in a dose dependent manner. Further studies were performed with a specific protein kinase C inhibitor, H-7 (1-(5-isoquinolinesulfonyl)-2-methyl-piperazine) and a specific cyclic adenosine monophosphate-dependent protein kinase inhibitor, IP-20. Basal release of CRF-41 from the cultured hypothalamic cells was unaffected by IP-20 and was only diminished at a high (50 microM) concentration of H-7. 5-HT stimulated-CRF release, however, was blocked by both H-7 and IP-20. Dexamethasone and aldosterone both caused a dose-dependent inhibition of 5-HT induced CRF release. These results demonstrate that CRF can be released from hypothalamic neurons in response to 5-HT through a protein kinase C and protein kinase A dependent mechanism and that 5-HT stimulated CRF release can be inhibited by dexamethasone and aldosterone. PMID- 1638401 TI - Neuroanatomical specificity in the autoregulation of aromatase-immunoreactive neurons by androgens and estrogens: an immunocytochemical study. AB - Testosterone (T) increases brain aromatase activity (AA) in quail and other avian and mammalian species. It was shown both in quail and in rat that this enzymatic induction results from a synergistic action of androgens and estrogens. These studies provide little information on possible anatomical or cellular specificity of the effect. Using a polyclonal antiserum against human placental aromatase, we have previously identified aromatase-immunoreactive (ARO-ir) neurons in the quail brain and demonstrated that T increases the number of ARO-ir cells in the quail preoptic area (POA) supporting previous evidence that T increases AA in the brain. However, which T metabolites are involved, the actual mechanism of regulation and the possibility of anatomical specificity for these effects are not yet clear. In the present study, we disassociated the effects of androgens and estrogens in aromatase induction by comparing ARO-ir neurons of quail treated with T alone or T in the presence of a potent aromatase inhibitor (R76713), which has been shown to depress AA levels and to suppress T-activated copulatory behavior. T increased the number of ARO-ir cells in POA, bed nucleus striae terminalis (BNST) and tuberal hypothalamus (Tu). The T effect was inhibited by concurrent treatment with aromatase inhibitor in Tu, but not in POA and BNST. This differential effect of the aromatase inhibitor fits in very well with our previous studies of the co-localization of aromatase and estrogen receptors. The T effect was blocked by R76713 in areas where ARO-ir and estrogen receptor-ir are generally co-localized (Tu) and was not affected in areas with mainly ARO-ir positive, estrogen receptor-ir negative cells (POA, BNST). This suggests anatomical differences in the expression or clearance of aromatase which may be differentially sensitive to androgens and estrogens and dependent upon the presence of sex steroid receptors. PMID- 1638402 TI - Interneurons in the rat striatum: relationships between parvalbumin neurons and cholinergic neurons. AB - A pre-embedding double-labeling immunocytochemical method was used to examine the synaptic relationships between cholinergic neurons and the parvalbumin immunoreactive (PV+) neurons. The PV+ neurons were labeled by silver-intensified colloidal gold particles, and the cholinergic neurons by immunoperoxidase reaction products. Cholinergic and PV+ axon terminals form synapses with both the somata and dendrites of PV+ neurons, as well as unlabeled medium-sized somata with round un-indented nuclei, a typical characteristic of the medium spiny projection neurons. These observations suggest that the PV+ and the cholinergic neurons have converging influences on both the projection neurons and the PV+ interneurons in the striatum. PMID- 1638404 TI - Bulbar reticular neurons relaying somatosensory information to the mesencephalic parabrachial area of the cat. AB - Somatosensory neurons projecting to the mesencephalic parabrachial area (MPBA), which is located ventral to the inferior colliculus and dorsal to the brachium conjunctivum, were recorded from the bulbar reticular formation of adult cats anesthetized with alpha-chloralose. The majority (41 of 50 neurons) were nociceptive-specific neurons responding only to noxious mechanical and/or thermal stimuli to the skin, cornea and/or oral mucosa. The size of their receptive fields was smaller than that of the intrinsic MPBA-neurons, but larger than that of the trigeminal sensory nucleus neurons. Twenty-three neurons received input from the tooth pulp nerve and 10 of 32 neurons tested responded to electrical stimulation of the vagal nerve. These results indicate that these bulbar reticular neurons receive noxious inputs and transmit them to the MPBA, which also receives input from spinal or trigeminal sensory nucleus neurons projecting directly to the MPBA. PMID- 1638403 TI - Electrical stimulation of nucleus tractus solitarius excites vagal preganglionic cardiomotor neurons of the nucleus ambiguus in rats. AB - Recent evidence indicates that the cell bodies of vagal cardioinhibitory neurons are located principally in the external formation of the nucleus ambiguus (NA). As activation of baroreceptor afferent fibers projecting to the nucleus tractus solitarius (NTS) elicits a decrease in heart rate it is likely that there is a connection between the NTS and NA. To test the hypothesis that stimulation of the NTS can excite vagal preganglionic cardiomotor neurons (VPCN) in the NA, activity from 78 neurons in the NA was recorded extracellularly before and during stimulation of a depressor site in the NTS (1 Hz, 0.1 ms) in urethan anesthetized and artificially ventilated male Wistar rats. Sixteen neurons were characterized as vagal preganglionic cardiomotor neurons (VPCN) because they were excited by baroreceptor activation (1-3 micrograms phenylephrine i.v.) and showed rhythmicity of their spontaneous activity in synchrony with the cardiac cycle. Stimulation of the NTS increased the firing rate of all these VPCN. The remaining 62 neurons could not be considered as VPCN because they either had respiratory rhythmicity or were not sensitive to baroreceptor activation, or they were sensitive to baroreceptor activation but did not display cardiac cycle related rhythmicity. These results provide evidence for the existence of an excitatory pathway from NTS to vagal preganglionic cardiomotor neurons in the NA. PMID- 1638406 TI - Cross-adapted salt responses in the mouse taste cell. AB - The exact nature of taste adaptation is not known. Intracellular recordings from taste receptor cells are appropriate to clarify cellular adaptation properties. I approached the study of the sugar and salt receptor mechanisms of mammalian taste cells with cross-adaptation experiments. Sucrose pre-adaptation suppresses the cross-adaptation responses to salts. The results show that the taste adaptation is located in the taste receptor cell. PMID- 1638405 TI - Secretion from rat neurohypophysial nerve terminals (neurosecretosomes) rapidly inactivates despite continued elevation of intracellular Ca2+. AB - Cytoplasmic calcium concentration was measured in neurosecretory nerve terminals (neurosecretosomes) isolated from rat neurohypophyses by fura-2 fluorescence measurements and digital video microscopy. Hormone release and cytoplasmic calcium concentration were measured during depolarizations induced by elevated extracellular potassium concentration. During prolonged depolarizations with 55 mM [K+]o, the cytoplasmic calcium concentration remained elevated as long as depolarization persisted, while secretion inactivated after the initial sharp rise. The amplitude and duration of the increase in [Ca2+]i was dependent on the degree of depolarization such that upon low levels of depolarizations (12.5 mM or 25 mM [K+]o), the calcium responses were smaller and relatively transient, and with higher levels of depolarization (55 mM [K+]o) the responses were sustained and were higher in amplitude. Responses to low levels of depolarization were less sensitive to the dihydropyridine calcium channel blocker, nimodipine, while the increase in [Ca2+]i induced by 55 mM [K+]o became transient, and was significantly smaller. These observations suggest that these peptidergic nerve terminals possess at least two different types of voltage-gated calcium channels. Removal of extracellular sodium resulted in a significant increase in [Ca2+]i and secretion in the absence of depolarizing stimulus, suggesting that sodium-calcium exchange mechanism is operative in these nerve terminals. Although the [Ca2+]i increase was of similar magnitude to the depolarization-induced changes, the resultant secretion was 10-fold lower, but the rate of inactivation of secretion, however, was comparable. PMID- 1638408 TI - Hippocampal pyramidal cell response to 6-hydroxydopamine lesions of the rat ventral tegmental area. AB - The occurrence of neurofibrillary tangles (NFT) in the perforant pathway in association with dopaminergic cell loss in the ventral tegmental area (VTA) in human mesolimbic dementia, raises the possibility that denervation is a cause of NFT formation. This was tested in the rat by lesioning dopaminergic neurons which project to the hippocampus from the ventral tegmental area by means of stereotaxic injections of 6-hydroxydopamine. This resulted in the appearance of immunoreactivity to the paired helical filament protein plus an increase of tau and MAP-2 proteins in pyramidal neurons of CA-1 and CA-2. These neuronal responses to dopaminergic denervation are consistent with a precursor stage to NFT development. PMID- 1638409 TI - Differential vulnerability of neuropeptides in nerves of the vasa nervorum to streptozotocin-induced diabetes. AB - Neuropeptides in perivascular nerves of vasa nervorum supplying blood to rat optic, sciatic, vagus and sympathetic chain nerve trunks are differentially vulnerable to streptozotocin (STZ)-induced diabetes. Immunohistochemical analysis of epineurial/perineurial nerve sheaths showed that 8 weeks after induction of diabetes, the density of neuropeptide Y (NPY)-immunoreactive nerve fibres in optic nerve sheaths was increased, while it was decreased in sciatic, vagus and sympathetic nerve sheaths. Vasoactive intestinal polypeptide (VIP) immunoreactivity was increased in vasa and nervi nervorum of optic, sciatic, vagus and sympathetic chain nerve sheaths. Immunoassay of NPY confirmed increased levels in optic nerve sheaths and showed that substance P and calcitonin gene related peptide levels increased in sciatic but not optic nerve sheaths. Neuropeptide levels in the intrafascicular nerve fibres were unaffected. This provides further evidence for a disturbance in the autonomic control of blood flow to peripheral and cranial nerve trunks via vasa nervorum in STZ-induced diabetes, which may lead to ischaemic changes, alter local axon reflexes and contribute to the pathogenesis of the disease. PMID- 1638410 TI - Remote astrocytic response of prefrontal cortex is caused by the lesions in the nucleus basalis of Meynert, but not in the ventral tegmental area. AB - The nucleus basalis of Meynert (nbM) was lesioned by injection of ibotenic acid, in 200 g male Wistar rats. The rats were killed 1, 3, 7 or 21 days after surgery, the brains were removed and the prefrontal cortices were subjected to immunohistochemical and Western blot analysis for the expression of glial fibrillary acidic protein (GFAP). In some rats, vehicle was injected into the nbM and in others 6-hydroxydopamine (6-OHDA) was injected into the ventral tegmental area (VTA). Quantitative Western blot analysis revealed significantly greater immunoreactivity for GFAP in the prefrontal cortex of nbM-lesioned rats. Immunohistochemical examination revealed fibrous and hypertrophic GFAP-positive astrocytes even one day after surgery, and this reaction was stronger at 3 days after surgery. After this peak, GFAP-immunoreactivity of the astrocytes decreased from 7 days to 21 days. In contrast, GFAP-positive astrocytes were not observed in the brains of vehicle-injected or VTA-lesioned rats, even 21 days after surgery. The present results indicate that cortical astrocytes respond to cholinergic deafferentation. In addition, our findings provide new insights into the abnormalities of cortical glial cells after cholinergic deafferentation in Alzheimer's disease. PMID- 1638407 TI - Chronic estradiol administration did not cause loss of hypothalamic LHRH or TIDA neurons in young or middle-aged C57BL/6J mice. AB - Age-related decline in estrous cycle frequency and impaired pre-ovulatory gonadotropin surges at mid-life are modelled in young C57BL/6J mice by chronic (3 months) oral administration of estradiol (E2). However, the cellular events that induce damage to the neuroendocrine center that regulate gonadotropins with age or following E2 treatment are unclear. To address this issue, possible neuron loss was examined in relation to the loss of estrous cyclicity in E2-treated mice, in particular neurons of the hypothalamic luteinizing hormone releasing hormone (LHRH) and/or tuberoinfundibular dopaminergic (TIDA) systems. By immunocytochemical methods, there was no change in the number of LHRH or TIDA neurons in mice that have become acyclic due to age or E2 treatment. We conclude that the onset of acyclicity at middle-age or following chronic E2 treatment is not associated with loss of LHRH or TIDA neurons and that other neuroendocrine changes must be considered for the cause of acyclicity, particularly those involved in the synaptic regulation of LHRH secretion. PMID- 1638411 TI - CRF in the paraventricular nucleus of the hypothalamus induces dose-related behavioral profile in rats. AB - Corticotropin-releasing factor (CRF) administered into the cerebrospinal fluid (CSF) alters grooming and locomotion in rats. The present study was designed to investigate if CRF microinjected into the paraventricular nucleus of the hypothalamus (PVN) influences grooming and spontaneous locomotor behavior in fasted rats maintained in a familiar environment. Unilateral microinfusion of CRF (0.06, 0.2 and 0.6 nmol) into the PVN induced a dose-related increase in grooming, whereas locomotion was dually affected. At lower doses of CRF (0.06 and 0.2 nmol) spontaneous locomotion was significantly increased. At the highest dose, locomotor activity was markedly reduced and, in about 30% of animals, freezing behavior occurred intermittently. The behavioral effects of CRF were maintained throughout the 60 min post injection period. Microinjection of CRF (0.2 nmol) into the lateral hypothalamus, or outside of PVN boundaries had no effect on these behavioral parameters. These results demonstrate that the PVN is a selective and potent site of action for CRF to induce a dose-dependent range of alterations in grooming and locomotion that mimics those observed after CSF injection in a familiar environment. These data also suggest that CRF in the PVN may be involved in mediating behavioral activation and the anxiogenic effect. PMID- 1638414 TI - Effects of intracerebral administration of neuropeptide-Y on secretion of luteinizing hormone in ovariectomized sheep. AB - Ovariectomized ewes received unilateral infusions of 20 micrograms neuropeptide-Y (NPY) at a total of 13 intracerebral sites. Episodic secretion of luteinizing hormone (LH) was transiently suppressed on more than one occasion by daily infusions at a total of five intracerebral sites. Four of the effective sites were located within the third ventricle (two sites) and the rostral and ventral part of a lateral ventricle (two sites). The precise neural site of action of exogenous NPY cannot be determined from intraventricular administration, but it indicates a neural rather than pituitary site of NPY action to inhibit LH releasing hormone (LHRH) in sheep. The only tissue infusion site (ventromedial nucleus) at which NPY also suppressed LH/LHRH also supports a neural action on LHRH, but this single result is insufficient to establish the neural area at which NPY acted. It is known from other work that the production of endogenous NPY in neural tissue of underfed animals is increased, and if endogenous NPY exerts effects on LH/LHRH similar to the suppression presently observed following exogenous NPY this neuropeptide might serve as one neuroendocrine factor that suppresses reproduction in underfed animals. PMID- 1638412 TI - Behavioural and neurohistological changes in aging Sepia. AB - The life cycle of the cuttlefish in the English Channel is characterized by a succession of homogeneous population cohorts. These conditions provide an excellent opportunity for the study of aging in this cephalopod. In a first longitudinal study, we considered the oldest animals and compared their success rates at the first capture attempt. During the first weeks of the study, the results remained constant and then, during the weeks immediately preceding the natural death, a dramatic drop was observed. This deterioration may be due to defects of visuomotor coordination. In a second study, we used an associative learning protocol with negative reinforcement and the performances of young and old animals were compared. The most striking results showed that the performances of the oldest animals during the retention test were very mediocre. Such results suggest that the long-term memory process is affected. Finally, a modification of the Fink-Heimer silver stain enabled us to draw a map of spontaneous terminal degeneration in the central nervous system of the oldest animals. The structures which are characterized by the presence of multimodal inputs (the spine of the peduncle lobe and the basal lobes) present the most obvious signs of degeneration. PMID- 1638415 TI - Third ventricular subependymal oxytocin-like immunoreactive neuronal plexus in the rat. AB - In a previous retrograde tracing study, a dense subependymal neuronal plexus was found along the anterior ventral third ventricle that projects to the posterior pituitary. In the work reported here, the oxytocin-like immunoreactive neurons of this plexus were studied in detail. It has a population of about 650 cells with a great wealth of dendrites. The neurons are of magnocellular neurosecretory type with long straight dendrites running parallel to the ependyma. The plexus is composed of a dorsal and a ventral part. The dorsal part consists of about 75% of the whole population and is most dense at the levels of the anterior and medial magnocellular paraventricular nuclei. Their dendrites appear vacuous in immunohistochemically stained sections and have a tendency to form fascicles. The ventral part is more sparse. The dendrites of the subependymal plexus are well organized so the anteriorly located ones tend to be directed rostrally and the posteriorly ones caudally. The functional significance of the plexus is discussed. PMID- 1638413 TI - Comparison of atropine pre- and post-treatment in ganglion neurons exposed to soman. AB - The prevention and reversal of the effects of soman (pinacoloxymethylphosporyl fluoride) have been examined on the electrical properties of sympathetic ganglion neurons in vitro from the adult bullfrog Rana catesbeiana. Atropine (10 microM) pre-treatment (before soman) blocked the soman-induced decrease in the membrane potential, membrane resistance, and afterhyperpolarization (AHP) duration. Atropine post-treatment (after soman exposure) restored the soman-induced decrease in the membrane potential but was ineffective in reversing either the membrane resistance or the duration of the AHP. These results demonstrate: 1) that the effects of soman on the electrical properties of these neurons are mediated by the activation of muscarinic receptors, 2) that following receptor activation different cellular mechanisms may be involved in the regulation of the electrical properties of the neuron, and 3) pre-treatment rather than post treatment with atropine is more effective in blocking these direct effects of soman. These results are discussed in reference to the increased effectiveness of atropine pretreatment in the protocols for soman-induced neurotoxicity. PMID- 1638416 TI - Enhancement of glutaminase-like immunoreactivity in rat brain by an irreversible inhibitor of the enzyme. AB - Changes of glutaminase immunoreactivity in rat brain were examined after intracranial injection of 6-diazo-5-oxo-L-norleucine (DON), an irreversible inhibitor of glutaminase. When 1 M DON was injected into the lateral ventricle, a half-lethal dose was 7.5-10 mumol. After intraventricular injection of 2-7.5 mumol DON, glutaminase immunoreactivity was dose dependently enhanced with the maximum enhancement 3-5 days after the injection. The enhanced glutaminase immunoreactivity was recognized by enlarged granular immunodeposits in both perikarya and neuropil in many regions, such as the hippocampus, thalamus, hypothalamus, periaqueductal gray, and some brain stem, cerebellar, and spinal cord regions. Intrathalamic injection of 0.2 mumol DON enhanced glutaminase immunoreactivity in many neuronal perikarya in the thalamus and in some perikarya in layer VI of the cerebral cortex. Intrastriatal injection of the same dose of DON enhanced glutaminase immunoreactivity in neuropil of the caudoputamen and in many neuronal perikarya of the intralaminar thalamic nuclei. These results suggested that DON induced a new massive synthesis of glutaminase in the affected neurons. PMID- 1638418 TI - Effects of noradrenergic DSP4 lesion on the effectiveness of pilocarpine in reversing scopolamine-induced amnesia. AB - We studied the effectiveness of pilocarpine in reversing the scopolamine-induced water maze learning deficit (increase in escape latencies, decrease in spatial bias) in control and DSP4- (a noradrenergic neurotoxin) lesioned rats. The water maze acquisition deficit (escape latency, first spatial bias) induced by scopolamine 0.8 mg/kg was augmented by DSP4 treatment. The water maze performance deficit induced by scopolamine was reversed by pilocarpine 4 mg/kg in both DSP4 lesioned and control rats. A smaller dose of pilocarpine (1 mg/kg) did not reverse scopolamine-induced acquisition deficit in either control or DSP4 lesioned rats. Analysis of the second spatial bias test measured 2 weeks after training revealed that pilocarpine 4 mg/kg reversed scopolamine-induced retention deficit in control and DSP4-lesioned rats. Pilocarpine 1 mg/kg reversed scopolamine-induced retention performance deficit during the second spatial bias test in control but not in DSP4-lesioned rats. The present results suggest that 1) noradrenergic and cholinergic systems may interact in the regulation of spatial acquisition and retention and 2) the effectiveness of cholinergic drugs in reversing scopolamine-induced spatial retention deficit may be affected by noradrenergic lesioning. PMID- 1638417 TI - AV3V lesion reduces the pressor, dipsogenic, and natriuretic responses to ventromedial hypothalamus activation. AB - In the present study, we investigated the effect of anteroventral third ventricle (AV3V) lesion on pressor, tachycardic, dipsogenic, natriuretic, and kaliuretic responses induced by the injection of the cholinergic agonist carbachol into the ventromedial hypothalamic nucleus (VMH) of rats. Male rats with sham or AV3V lesion and a stainless steel cannula implanted into the VMH were used. Carbachol (2 nmol) injected into the VMH of sham rats produced pressor (32 +/- 4 mmHg), tachycardic (83 +/- 14 bpm), dipsogenic (8.2 +/- 1.1 ml/h), natriuretic (320 +/- 46 microEq/120 min), and kaliuretic (155 +/- 20 microEq/120 min) responses. In AV3V-lesioned rats (2 and 15 days), the pressor (4 +/- 2 and 15 +/- 2 mmHg, respectively), dipsogenic (0.3 +/- 0.2 and 1.4 +/- 0.7 ml/h), natriuretic (17 +/- 7 and 99 +/- 21 microEq/120 min), and kaliuretic (76 +/- 14 and 79 +/- 7 microEq/120 min) responses induced by carbachol injection into the VMH were reduced. The tachycardia was also abolished (27 +/- 15 and -23 +/- 29 bpm, respectively). These results show that the AV3V region is essential for the pressor, tachycardic, dipsogenic, natriuretic, and kaliuretic responses induced by cholinergic activation of the VMH in rats. PMID- 1638419 TI - Postnatal development of the locus coeruleus in trisomy 19 mice: morphological and morphometric study. AB - To study the effect of trisomy upon a brain region that is generated very early during development, the locus coeruleus (LC) has been examined morphologically and morphometrically in 23 Trisomy 19 (Ts19) mice and their chromosomally balanced control littermates aged 2-18 days postpartum. Gross morphological alterations of the Ts19 LC could neither be observed by light nor by electron microscopy. The LC was properly located. Ultrastructural features indicating increasing protein synthesis such as nucleolus-like bodies and a rise in the amount of granular endoplasmic reticulum and in the size of the nucleoli have been observed both in Ts19 and control mice. Maturation of the LC was delayed in Ts19. Morphometric studies on the volume, cell number, and cell density revealed that, apart from a 2-day delay in development, the Ts19 LC was of normal size. The present study supports the observation that the noradrenergic system is not affected in the Ts19 CNS. Taking into account that the cerebellum of Ts19 mice is markedly hypoplastic, the results indicate a differential pathogenic effect of trisomy upon different neural systems. PMID- 1638420 TI - Neurochemical and morphological evidence of an antinociceptive neural pathway from nucleus raphe dorsalis to nucleus accumbens in the rabbit. AB - Previous studies using a pharmacological approach suggested a neural pathway emanating from the periaqueductal gray (PAG) to the nucleus accumbens relevant to antinociception. This was investigated with neurochemical and histochemical methods in the present study. Push-pull perfusion and radioimmunoassay were used to measure the release of immunoreactive-(ir) enkephalin (ir-ENK) and ir-beta endorphin (ir-beta-EP) in the nucleus accumbens after microinjection of morphine into the PAG and the nucleus raphe dorsalis (NRD) of the rabbit. Morphine administration elicited an increase in ir-ENK and ir-beta-EP in the nucleus accumbens. Horseradish peroxidase (HRP) retrograde tracing in combination with 5 hydroxytryptamine (5-HT) immunocytochemistry revealed a serotonergic projection from the NRD and ventral PAG to the nucleus accumbens in the rabbit. About 7% of the serotonin-positive cells in the NRD and ventral PAG send fibers directly to the nucleus accumbens, with an ipsilateral dominance. These results indicate the existence of a serotonergic pathway from the NRD to the N. accumbens involved in opioid analgesia. PMID- 1638423 TI - The diaphragm. AB - Intrinsic disorders of the diaphragm are uncommon. However, the diaphragm is a useful radiographic landmark for detecting adjacent pulmonary, pleural and abdominal abnormalities, which may lead to the elevation of one or both hemidiaphragms or to focal irregularities in the diaphragmatic contour. In this review the authors summarize the most common diaphragmatic abnormalities and suggest the optimal approach for each to allow a specific diagnosis. PMID- 1638421 TI - Serotonin-CRF interaction in the bed nucleus of the stria terminalis: a light microscopic double-label immunocytochemical analysis. AB - The purpose of the present study was to examine in the bed nucleus of the stria terminalis (BST) of the rat brain the morphological characteristics of interactions between corticotropin-releasing factor (CRF)-producing neuron populations and serotonin (5-HT) axons. A double-label immunocytochemical, light microscopic technique was used to demonstrate axosomatic and axodendritic interactions between 5-HT axons and CRF neurons in the BST. Both the dorsolateral and ventrolateral subpopulations of CRF neurons were targets for the 5-HT afferents. Projections of monoamine neurons to the BST and the CRF neurons that are in the BST are implicated as being major contributors to the neurochemically mediated central regulation of the stress response. PMID- 1638426 TI - Pulmonary edema complicating upper airway obstruction in infants and children. AB - The association of pulmonary edema with upper airway obstruction occurs in three clinical settings: acute and chronic upper airway obstruction and immediately after the relief of acute upper airway obstruction. Iatrogenic causes, such as adenotonsillectomy and tracheal intubation, were the most frequently encountered in the authors' series of 21 pediatric patients with such an association. The pathogenesis of this kind of pulmonary edema is multifactorial. The application of moderate continuous positive airway pressure in conjunction with the administration of diuretics rapidly clears pulmonary edema in all three clinical settings, usually within 24 hours, and can probably prevent pulmonary edema immediately after acute obstruction is relieved. PMID- 1638424 TI - Peripancreatic fluid collections: vascular structures masquerading as pseudocysts. AB - Five patients with splanchnic arterial aneurysms and one patient with a tortuous splenic vessel presented with peripancreatic masses that exhibited an anechoic portion in real-time ultrasonography (US) images; the masses were incorrectly diagnosed as pseudocysts. In two patients a vascular abnormality was suspected, and colour-flow Doppler and pulsed Doppler US were performed; these techniques showed the presence of pseudoaneurysms. In the other four patients the possibility of a pseudoaneurysm was not entertained until further studies had been performed. These results emphasize the need for colour-duplex US evaluation of all peripancreatic fluid collections during the initial US examination to avoid the misinterpretation of an aneurysm or a pseudoaneurysm as a simple or complex fluid collection and to prevent the potential disaster of performing biopsy, surgery or other interventions. PMID- 1638425 TI - Estimation of splenic weight from ultrasonographic measurements. AB - The author assessed the predictability of the weight of a resected spleen from measurements obtained from real-time ultrasonography (US) scans. In a preliminary study of 12 spleens obtained at autopsy and then examined by US the product of splenic length, width and thickness was linearly related to splenic weight (R2 = 0.97, r = 0.92, p less than 0.001). In a subsequent retrospective study of 81 patients who had undergone a total of 101 abdominal US examinations within 4 months of death and whose spleens were weighed during autopsy, splenic weight in grams was equal to 0.43 (length x width x thickness) for measurements in centimetres (R2 = 0.92, r = 0.78, p less than 0.001). Estimation of splenic weight is therefore possible by a simple calculation; this method offers an alternative to subjective assessment of spleen size, and the information it provides compares well to established norms. PMID- 1638422 TI - Effects of spontaneous bioelectric activity and gangliosides on cell survival in vitro. AB - Chronic suppression of spontaneous bioelectric activity in spinal cord explants in the presence of tetrodotoxin (TTX) during network formation caused a large reduction in cell number (lowered DNA levels). The addition of gangliosides failed to protect against this cell loss. Conversely, the omission of galactose from the growth medium had no effect on DNA levels. It was concluded that the presence or absence of afferent selectivity is unlikely to require the survival of a regionally specific subpopulation of preferred dorsal root ganglion target cells. Neocortical explants also showed a large reduction in DNA levels following chronic TTX treatment, and morphometric analysis confirmed that neuronal survival was affected to the same degree. Chronic ganglioside supplementation failed to influence DNA and cell counts in either control or TTX-treated explants, but one of the added gangliosides (GD1a) stimulated extensive neuritic outgrowth in electrically silenced cultures. Particular ganglioside species, therefore, may exert a growth stimulating influence that can partially compensate for the absence of bioelectric self-stimulation during early development. PMID- 1638427 TI - Reprint requesters and providers in radiology. AB - After the publication of any medical paper, its authors normally receive requests for reprints. An analysis was performed to determine the geographic origin of requests, the frequency of requests and the response rate for individual requesters, the additional work that these requests entail for major authors and some of the associated costs. A total of 209 consecutive reprint requests received over a 11-month period for radiologic articles written by one of the authors of this paper were reviewed. Overall, 45% of the requests originated in the United States, 22% in Western Europe (excluding Britain), 19% in Eastern Europe, 8% in Canada, 4% in Britain and 2% collectively in India, Cuba and Mexico. A questionnaire was sent to each requester; 122 (58%) replied. The respondents requested between 3 and 2000 reprints each year; respondents from the United States requested by far the most reprints. The respondents received reprints for between 25% and 100% (mean, 70%) of their requests. The requesters found the articles in the original journal in 41% of cases, in Current Contents (ISI Press, Philadelphia) in 34%, in both the journal and Current Contents in 23% and in other sources in 2%. Twenty-seven of 39 frequently published authors (69%) replied to a questionnaire about the requests they received; 19 reported receiving at least 100 requests and 4 at least 500 requests every year. Inquiries to 29 radiologic journals about the cost of reprints and the frequency of requests for additional copies yielded 18 replies. Twelve journals provided free reprints, and for the other 6 the average cost of 100 reprints was $90 (Can) when the reprints were ordered at the time of the original printing (as offprints). PMID- 1638428 TI - Complete duplication of the bladder and the urethra with associated anomalies. PMID- 1638429 TI - Management of postnephrolithotomy perforation of the renal vein by a double catheter technique. AB - Significant venous bleeding after nephrolithotomy is a relatively frequent and well-described complication. The authors report a case of renal vein perforation and its management through combined flank and groin access to the site of bleeding. PMID- 1638431 TI - Subarachnoid hemorrhage resulting from methanol intoxication: demonstration by computed tomography. AB - Subarachnoid hemorrhage developed in a patient intoxicated with methanol. Computed tomography performed at the time of admission suggested this complication. The hemorrhage was definite and extensive by the 5th day after admission and was accompanied by left caudate and pontine hemorrhage, as well as severe cerebral edema. The authors are unaware of any previous reports of subarachnoid hemorrhage associated with ingestion of methanol. PMID- 1638430 TI - Pseudoaneurysm of the inferior gluteal artery. AB - Aneurysms of the inferior gluteal artery are uncommon, and have not previously been described in detail in the radiologic literature. The authors report the findings of computed tomography and angiography for a patient with a pseudoaneurysm of the inferior gluteal artery who was successfully treated by embolization alone. PMID- 1638432 TI - Answer to case of the month #14. Tornwaldt's cyst of the nasopharynx. PMID- 1638433 TI - [Implication of growth hormone in experimental induction of vitellogenesis by estradiol-17 beta in female silver eel (Anguilla anguilla L.)]. AB - The effect of different preparations of growth hormone (GH) was assayed with 17 beta-estradiol on vitellogenesis in hypophysectomized or normal female silver eels. Vitellogenin (Vg) plasma levels were taken as the index of hepatic vitellogenesis. The E2 doses were chosen to give the same pattern for the plasma Vg level as in the controls. They decreased or remained undetectable in hypophysectomized or normal animals. GH also failed to induce alone a significant modification. When E2 was injected together with a GH, plasma Vg levels were 5.13 +/- 1.30 times higher with salmon GH in hypophysectomized eels and 2.01 +/- 0.25 times higher with bovine GH in normal eels. GH is shown to enhance the effects of E2 on hepatic vitellogenesis induction in a teleost. PMID- 1638434 TI - Transport of the critically ill. PMID- 1638436 TI - Education of personnel involved in the transport program. AB - Inclusive in the demand for transport services is the need for an ongoing formal educational curriculum to ensure that a high standard of care is consistently provided to patients. Those who provide transport services must ensure that the staff has an adequate baseline level of training and licensure, an ongoing system of educational review, and the frequency of activity necessary to maintain skills. Team members should have an acceptable level of cognitive and technical skills to transport patients and perform needed procedures safely. Such skills may be acquired and maintained by participation in nontransport activities, through a didactic curriculum and a system of ongoing case review, through team members providing training to referring hospitals, and through a "buddy" system of supervised transport activities. While an ongoing educational curriculum and its structure remain constant, the content can and should be tailored to the type of patients transported, from the very low birth weight infant and pregnant mother to pediatric and adult patients. PMID- 1638435 TI - The nuts and bolts of organizing and initiating a pediatric transport team. The Sutter Memorial experience. AB - Specialized interfacility transport teams are capable of delivering critical care medicine to the patient at the referring hospital and while en route to the tertiary care center. To do so effectively, however, requires adequate financial and human resources; management of equipment, supplies and personnel; ongoing education for transport team members; and an aggressive quality assurance program. Team members and team management should always be prepared for worst case scenarios, and develop a method for problem resolution as troublesome issues arise. The ultimate goal of serving the needs of the critically ill child can be consistently met only if there is a high level of commitment of all involved- from the hospital administrator and medical director to the transport coordinator and team members. PMID- 1638437 TI - Critical incident stress debriefing in health care. AB - Transport team professionals have unique responsibilities and are exposed to powerful demands. They cannot avoid incidents that pose personal threats to their own emotional well being. Contact with dead or severely ill or injured children, for example, can be detrimental to the caregiver. Discussions called debriefings held after these critical incidents can decrease acute and delayed stress reactions. PMID- 1638439 TI - Interhospital transport. A pediatric perspective. AB - Interhospital transport of children must not be undertaken in a vacuum. Basic medical ethics and federal laws demand that there be some responsibility in providing adequate care during the transport process, and that this care meets or exceeds the level provided by the referring hospital. The care provided must also be appropriate to the severity of illness of the transported children. National guidelines and standards are needed to establish and coordinate a uniform interhospital transport process for critically ill children. PMID- 1638440 TI - Intrahospital transport of critically ill patients. AB - Intrahospital transport of critically ill patients must be considered as part of the critical care continuum. The level of care provided must be commensurate with the severity of illness. These transfers are intensive in terms of utilization of personnel and resources. Advance preparation and optimal coordination of the transport process go a long way toward safer transfers of the critically ill. PMID- 1638438 TI - Medical-legal considerations involved in the transport of critically ill patients. AB - The author explains the basic elements of negligence and describes how these elements are complicated by the very nature of the transport process. The author also provides information on establishing a transport program that will minimize patient injury and protect the transport team from liability. A list of tips for avoiding liability is also included. PMID- 1638441 TI - Evaluation of ground ambulance, rotor-wing, and fixed-wing aircraft services. AB - It is hoped that this article has offered insightful suggestions and criteria in choosing the most appropriate method to transport patients. Ground ambulances, rotor-wing, and fixed-wing aircraft each have advantages and disadvantages in particular circumstances. The advantages and disadvantages of any mode of transport must be considered to best meet the needs of the patient. In the twentieth century alone, great strides have been made in the field of emergency stabilization and transport. An efficient, well-trained ground ambulance program remains the backbone of prehospital and interhospital transport systems. Helicopters and fixed-wing transports must be integrated into the EMS system. One advantage of the helicopter and fixed-wing aircraft is rapid travel times when time is critical. As Hicks et al said, "early resuscitation and timely transfer of selected patients are critical factors in reducing morbidity and mortality." The future holds many possibilities for enhanced patient transport. Hospitals may be able to use tilt-rotor, vertical landing, fixed-wing aircraft to combine the advantages of helicopter and fixed-wing aircraft. After all, our primary goal is to get the right patient, with the right personnel, to the right place in the right amount of time. PMID- 1638442 TI - Ten years of maternal-fetal transport. AB - One maternal-fetal transport system and the public health policies that supported its development are presented. System development, the components necessary for successful two-way maternal-fetal transports, and growth between 1981 and 1991 are summarized. PMID- 1638443 TI - Transport of critically ill patients in need of extracorporeal life support. AB - In the past 10 years, we have seen tremendous growth in the use of ECMO for neonatal cardiopulmonary failure, and new indications are being recognized for the use of ECMO and other forms of ECLS in older children and adults. The number of medical centers providing ECLS is and will always be limited, so services are needed to transport critically ill patients to ECLS centers. Transport teams should be thoroughly familiar with the pathophysiology of cardiac and respiratory failure. They should be equipped to continue the monitoring and treatment initiated at the referring center, to maintain that level of care during transfer, and to treat complications of the diseases or of the therapy itself. The responsibilities of the referring centers are to acquaint themselves with ECLS programs in their geographic areas and with transport services available. Early communication with complete and accurate information is essential. Developing a program for ECLS during transport is a huge undertaking that should be considered seriously. Not every ECLS center has the resources to embark on such a program. Timely referral should make such complex transfers unnecessary for most patients. PMID- 1638444 TI - Flight physiology. Clinical considerations. AB - Altitude-related complications and the stresses of flight represent the components of flight physiology. Understanding the complexities associated with patient management relative to barometric pressure changes and hypoxia is of paramount concern to air medical personnel. This article reviews flight physiology as well as appropriate precautions and interventions that must be practiced to provide optimal patient care at various altitudes. PMID- 1638445 TI - Management of the patient with head injury during transport. AB - The most important principles of initial management of the head-injured patient are rapid transport to an institution capable of providing the sophisticated evaluation, neurosurgical services, and monitoring necessary to improve outcome because definitive management of the head-injured patient is not possible in the field. The emphasis of care during stabilization and transport should be on the prevention of secondary central nervous system injury, primarily by prompt stabilization of the airway and assurance of proper ventilation and oxygenation, and by control of bleeding and provision of adequate circulation. PMID- 1638446 TI - Transport of the critically ill patient with upper airway obstruction. AB - Upper airway obstruction is a life-threatening emergency requiring prompt evaluation and careful intervention. The pathophysiology of upper airway obstruction is reviewed. Assessment techniques and stabilization are discussed with specific attention to intervention and stabilization prior to transport. PMID- 1638447 TI - Emotional impact on parents of transported babies. Considerations for meeting parents' needs. AB - The authors discuss the transport of critically ill newborns in relation to the psychological impact of attachment in pregnancy, transition to parenthood, and prenatal experience of a medical emergency. Interviews with parents and medical staff are included to provide an understanding of the experience from these perspectives. Considerations and recommendations are given for building an effective program to address the emotional needs of families of transported babies. PMID- 1638449 TI - [Preliminary results on the residence distribution at birth of patients with Alzheimer's disease in the Saguenay-Lac-Saint-Jean/Quebec (the IMAGE project)]. AB - The IMAGE Project is pursuing the establishment of a population-based registry of Alzheimer's disease (AD) cases in the Saguenay-Lac-Saint-Jean (SLSJ) (Quebec). The authors report on the spatial distribution at birth of 221 possible, probable and definite cases. A large network of key-informants for screening AD cases has been established over SLSJ. The spatial distribution of cases at birth and at the onset of disease has been computed by calculating the Alzheimer birth rate (ABR) on the basis of three scales: six specific geographical spheres of screening, all municipalities, and the public health departments. The statistical significance of results was determined using the theoretical Poisson and the Chi square distributions. ABR for each of the geographical spheres of screening showed no statistically significant differences considering either residence at the onset of the disease or residence at birth. Furthermore, differences were observed between rural and urban areas with an interesting trend for a higher number of cases than expected in one area of SLSJ. The spatial distribution of cases considered on the basis of residence at birth appears to show a different pattern, but no significant, from that measured on the basis of residence at the onset of disease. Screening of cases is actively being pursued all across SLSJ by the IMAGE network. There is a clear trend towards rural residence at birth of cases. It remains to see whether or not this observation is due to a geographical concentration of familial cases. PMID- 1638448 TI - Some aspects of adult mortality in developed countries. PMID- 1638451 TI - Psychosomatic medicine: specificity and integration. PMID- 1638450 TI - [Medical students facing their future career: a survey in Lille]. AB - A questionnaire was attached to the registration form which had to be filled out by the medical students in October 1990 at the Faculty of Lille, France. Among the 1660 respondents, 60% thought that there was an oversupply of medical manpower and nearly 50% were in favour of a stronger numerous clauses. Unified Europe was perceived as a threat to their future practice by 37% but 19% considered it as an additional opportunity. Private general practice was favoured only by 12% younger students and 50% "residents" (those who have failed to enter the courses of specialties). PMID- 1638453 TI - Seasonality in psychiatry--a review. AB - This paper reviews the literature pertaining to seasonal patterns in psychiatric illnesses. Evidence on the season of birth phenomenon suggests that a greater risk of pre-, peri-, or post-natal damage is associated with the winter months. There is currently insufficient evidence to pinpoint the exact mechanism involved or to ascertain whether the mechanism is common to each condition. Studies of seasonal patterns of incidence of psychiatric disorders have highlighted the role of seasonally regulated environmental factors on internal biological processes. There is growing evidence that serotonin is involved in a variety of psychiatric disorders. Seasonal patterns have been observed in processes involving serotonergic functioning. Furthermore, it has been postulated that these processes may be influenced by photoperiod, suggesting that the seasonal patterns of incidence of several psychiatric conditions may share a common neurophysiological substrate. PMID- 1638454 TI - Advances in diagnosis and treatment of anorexia nervosa and bulimia nervosa. AB - This paper reviews four areas of research into anorexia nervosa (AN) and bulimia nervosa (BN). First, in terms of diagnosis, the psychological concerns about weight and shape are now addressed in BN, bringing it more in line with the related disorder, anorexia nervosa. Second, studies of psychiatric comorbidity confirm the overlap between eating disorders and depression, obsessive compulsive disorder, substance abuse, and personality disorder. Nevertheless, there are reasons to accept the distinct qualities of each syndrome, and eating disorders are not merely a variant of these other conditions. Third, treatment advances in BN involve mainly cognitive-behavioural or interpersonal psychotherapies and pharmacotherapies primarily with antidepressants. The effect of combining more than one approach is beginning to be addressed. Finally, outcome studies involving people with both AN and BN have shown that the disorders "cross over" and that both conditions have a high rate of relapse. A renewed interest in the treatment of AN is needed. PMID- 1638452 TI - Psychophysiological contributions to phantom limbs. AB - Recent studies of amputees reveal a remarkable diversity in the qualities of experiences that define the phantom limb, whether painless or painful. This paper selectively reviews evidence of peripheral, central and psychological processes that trigger or modulate a variety of phantom limb experiences. The data show that pain experienced prior to amputation may persist in the form of a somatosensory memory in the phantom limb. It is suggested that the length and size of the phantom limb may be a perceptual marker of the extent to which sensory input from the amputation stump have re-occupied deprived cortical regions originally subserving the amputated limb. A peripheral mechanism involving a sympathetic-efferent somatic-afferent cycle is presented to explain fluctuations in the intensity of paresthesias referred to the phantom limb. While phantom pain and other sensations are frequently triggered by thoughts and feelings, there is no evidence that the painful or painless phantom limb is a symptom of a psychological disorder. It is concluded that the experience of a phantom limb is determined by a complex interaction of inputs from the periphery and widespread regions of the brain subserving sensory, cognitive, and emotional processes. PMID- 1638455 TI - Psychiatric morbidity during the early phase of coronary care for myocardial infarction: association with cardiac diagnosis and outcome. AB - We evaluated the association of psychiatric morbidity during the early phase of admission to a coronary care unit with cardiac diagnosis and subsequent morbidity. Ninety-two patients admitted for the first time for presumed myocardial infarction were evaluated within 48 hours of hospitalization. Anxiety and depressive symptoms and cognitive impairment were rated. Data were collected on cardiac diagnosis and morbidity. Three and 12 months after hospitalization, cardiac morbidity, psychiatric symptoms and psychosocial morbidity were assessed. PMID- 1638458 TI - A review of schizoaffective disorder: II. Somatic treatment. AB - Studies on the response of schizoaffective patients to somatic treatments are reviewed. Research suggests that in many cases the response of schizoaffective disorder to pharmacological intervention is similar to that of primary affective disorder. However, it is necessary to take into account the heterogeneity of the category when treating patients. The drugs used most frequently are lithium, neuroleptics (antipsychotics), antidepressants and anticonvulsants. Often a combination of drugs is found to be more effective than a single drug. Electroconvulsive therapy has been found to be very effective in the treatment of schizoaffective depression. PMID- 1638457 TI - A review of schizoaffective disorder: I. Current concepts. AB - This paper reviews recent literature on schizoaffective disorder. Research studies of diagnosis, clinical course and outcome and family history are evaluated. It is concluded that schizoaffective disorder is a heterogeneous category which includes patients with bipolar disorder, schizophrenia, a genetically distinct psychosis and a genetic disposition to both schizophrenia and bipolar disorder. PMID- 1638456 TI - A Canadian medical-psychiatric inpatient service. AB - Patients with both psychiatric and medical illnesses present complex and, at times, difficult diagnostic and management problems. Medical-psychiatric units designed to provide integrated medical and psychiatric care have been established in the United States. This paper describes the development and structure of such a unit established at a Canadian general hospital, using psychiatric facilities and resources already in place. A one year review of the characteristics of patients discharged from the service found that their mean length of stay was similar to that of inpatients discharged from the general adult inpatient services, but shorter than that of patients discharged from the psychogeriatric service. Many of these patients had neurological conditions; coexisting affective disorders, substance abuse, organic mental syndromes and somatoform disorders were diagnosed frequently. We believe that a medical-psychiatric inpatient unit can provide integrated care to patients who might otherwise receive less than adequate care. PMID- 1638459 TI - The prevention of sexual exploitation of patients: educational issues. PMID- 1638460 TI - Antiemetic drugs for chemotherapeutic support. Current treatment and rationale for development of newer agents. PMID- 1638462 TI - Biologic therapy of human cancer. PMID- 1638463 TI - The colony-stimulating factors. An overview. AB - Hemopoietic cell proliferation, differentiation, and function appear to be regulated by cytokines designated as colony-stimulating factors (CSF) or interleukins (IL) based on their original description. These cytokines are characterized by pleiotropic actions in multiple lineages and at multiple levels. Additionally, synergistic interactions are prominent, particularly at the level of early stem cells. Baseline regulation of hemopoiesis may be regulated by presentation of multiple growth factors at the bone marrow stromal cell surface. PMID- 1638461 TI - Managing chemotherapy-induced nausea and vomiting. A paradigm for supportive care. AB - BACKGROUND: Clinical research on the problem of chemotherapy-induced nausea and vomiting (N & V) originated out of the necessity of keeping patients engaged with aggressive treatment protocols. The degree of sophistication available today is reviewed. METHODS: A supportive care model is proposed for describing the developments as a six-step paradigm, ending with the suggestion that institutionalization is a final critical step in applying the results of research. CONCLUSIONS: The proposed model for control of N & V is suggested as a paradigm for the diffusion of a new technology designed to alleviate some aspect associated with suffering from the effects of cancer or its treatments. PMID- 1638465 TI - The role of hypoxia in renal production of erythropoietin. AB - Hypoxia is the fundamental stimulus for erythropoietin (EP) production. It is clear that hypoxia increases erythropoietin messenger RNA in a renal cell, which leads to the production of increased amounts of erythropoietin in the kidney. Hypoxia also increases external messenger substances that amplify the effects of hypoxia and increases erythropoietin messenger RNA to further accelerate erythropoietin production. Some of these messenger substances are adenosine, eicosanoids, oxygen-derived metabolites, and beta-2 adrenergic agonists that are postulated to act through the activation of cell membrane receptors and are coupled to an increase in a G stimulatory protein which activates adenylate cyclase. This leads to increased production of cyclic adenosine monophosphate (AMP) for the production of key phosphoproteins that are involved in the biosynthesis/secretion of erythropoietin. This paper considers the physicochemical properties of human erythropoietin, pharmacologic agents that increase and decrease erythropoietin production/secretion, serum erythropoietin levels in normal human subjects and in patients with several types of anemia, and a model for the role of adenosine and other external messenger substances in erythropoietin biosynthesis/secretion. PMID- 1638464 TI - The use of colony-stimulating factors in primary hematologic disorders. AB - BACKGROUND: The cloning of the human colony-stimulating factors (CSF), granulocyte CSF, granulocyte-macrophage CSF, and interleukin-3 has led to their use in a variety of clinical settings. RESULTS: These CSF have been used successfully to raise neutrophil counts and prevent or control infection in patients with neutropenia due to primary hematologic disorders. Their effects on platelet and erythrocyte counts have been modest; occasional patients have multilineage improvement in hematopoiesis. CONCLUSIONS: The CSF can be given for several months at effective and tolerable doses. Their long-term efficacies and toxicities remain to be elucidated, and the optimal dose and dosing schedule to be used for each indication are not defined currently. Although the CSF can improve hematopoiesis in patients with primary hematologic disorders, they are not curative. PMID- 1638466 TI - New agents for the treatment of multiple myeloma and non-Hodgkin lymphoma. AB - Several important new agents are effecting the management of non-Hodgkin lymphoma (NHL) and multiple myeloma. The two selected for review in this article include a biologic-response modifier and a new chemotherapeutic agent. The biologic response modifiers offer entirely new approaches to these diseases. The most extensively tested agent currently has been recombinant alpha-interferon (alpha IFN). The IFN are active, albeit weak, remission-induction agents for low-grade NHL and some T-cell lymphomas, but they appear to be ineffective as single agents in most intermediate-grade or high-grade NHL and myeloma. However, an emerging pattern in follicular lymphomas and myeloma is that alpha-IFN in combination with chemotherapy may lead to more complete and durable clinical responses and the increased prospect of prolonged disease control. Fludarabine, a new chemotherapeutic agent, is a promising drug with demonstrated activity in low grade lymphomas that parallels its impressive activity in chronic lymphocytic leukemia. PMID- 1638467 TI - The strategic use of antiestrogens to control the development and growth of breast cancer. AB - Tamoxifen has become the endocrine treatment of choice for all stages of breast cancer. Its low incidence of side effects and proven survival advantage observed during adjuvant therapy in postmenopausal women with node-positive disease has encouraged the use of long-term treatment for patients to benefit fully from therapy. The drug has an appropriate level of estrogen-like effects that could be beneficial to maintain bone density and prevent development of coronary heart disease by lowering circulating cholesterol. These effects might be useful in all patients with estrogen receptor-positive breast cancer who currently are receiving no therapy. This antiestrogenic agent could be effective therapy to deter recurrence, and the estrogen-like side effects support the physiologic processes of the patient as hormone-replacement therapy. In the laboratory, a tamoxifen-stimulated breast cancer model has been described in vivo. This form of drug resistance may occur in patients after long-term or indefinite adjuvant therapy. Novel pure antiestrogenic drugs have been discovered that soon will become available as second-line therapy after tamoxifen failure. In addition, tamoxifen is being evaluated in the United Kingdom as chemosuppressive therapy to prevent the development of breast cancer in high-risk women. A similar clinical evaluation is underway in the United States. PMID- 1638468 TI - Topical absorption and inactivation of cytotoxic anticancer agents in vitro. AB - BACKGROUND: Cytotoxic anticancer agents may pose carcinogenic or teratogenic risks to personnel who prepare or administer drugs to patients with cancer. METHODS: A series of laboratory studies were done to quantify the extent of percutaneous absorption and topical inactivation for various cytotoxic anticancer agents. Topical inactivation of anthracyclines and anthracene DNA intercalating agents was evaluated using Ames bacterial mutagenicity assays and reverse-phase high-performance liquid chromatography measurements. RESULTS: Drug levels passing through human abdominal skin exposed in vitro for 24 hours to 100 micrograms of daunorubicin, doxorubicin, and melphalan were negligible and typically less than the high-performance liquid chromatography sensitivity limit of 1-5 ng/ml (less than or equal to 0.001% possible absorption). Melphalan powder was recoverable from the air near a mortar and pestle used to crush 14 2-mg tablets manually; beyond 12 inches, no airborne drug was recoverable. A standard (4%) concentration of calcium hypochlorite completely inactivated the anthracyclines daunorubicin and doxorubicin but not mitoxantrone. This agent required treatment at a calcium hypochlorite concentration of 432 milligrams for complete inactivation. CONCLUSIONS: In summary, topical cytotoxic drug absorption is negligible (if it occurs at all). However, mechanical manipulations of oral formulations may present a risk of exposure to airborne drug particles. Concentrated calcium hypochlorite is extremely effective in the the topical inactivation of certain carcinogenic cytotoxic agents. PMID- 1638469 TI - Hazards of chemotherapy. Implementing safe handling practices. AB - Over the last decade, concerns about the hazards of handling cytotoxic chemotherapeutic agents increased as various studies were published. Analysis of these data suggest possible carcinogenic, teratogenic, and mutagenic risk for health professionals (predominantly nurses and pharmacists) that handle these drugs. However, the research is inconclusive. The nature of the problem, along with methodologic issues, may make it difficult or impossible to provide definitive data on the type and degree of risk for those exposed to chemotherapeutic agents. Guidelines and recommendations have been published by various groups including the Occupational Safety and Health Administration, the American Society of Hospital Pharmacists, the Oncology Nursing Society, and others. In essence, they recommend that only health professionals with specialized training should prepare or administer chemotherapeutic agents. In addition, equipment, unused drugs, and human excreta should be treated as chemically hazardous waste and disposed of according to the individual facility's policies and procedures. These guidelines should provide protection for those involved in preparing chemotherapy for administration, regardless of where this is done. Studies have shown differences in the degree and type of procedures followed and between existing procedures and actual practice. Some of these differences are based on the site of care (e.g., hospital [also influenced by bed size], private practice, or home care). Issues involved in implementing reasonable approaches to lower the relative risk for health-care professionals that handle cytotoxic chemotherapy will be discussed. PMID- 1638471 TI - Controversial issues in 5-fluorouracil infusion use. Dose intensity, treatment duration, and cost comparisons. AB - BACKGROUND: The use of ambulatory infusions of 5-fluorouracil (5-FU) improves the therapeutic index of this drug and is superior to the traditional schedule of bolus administration weekly or daily for 5 days at 5-week intervals. The infusion schedules that have been used vary as follows: (1) 24-hour infusion weekly; (2) 48-hour infusion weekly or biweekly; (3) 120-hour infusion at 4-5-week intervals; (4) 14-day infusion; and (5) protracted infusions continuously for 10 weeks or more. The relationship of dose intensity to infusion duration and the analysis of costs of chemotherapy were reviewed. METHODS: Selected clinical trials of infusional 5-FU were analyzed regarding infusion duration and dose intensity in relationship to response rates (RR). Chemotherapy cost was analyzed distinguishing "cost" definitions. RESULTS: The response rates for the infusion durations studied in Phase II and III trials were: (1) 24 hours, 25%; (2) 48 hours, 30%; (3) 120 hours, 3%; (4) 14-day, 12%; and (5) 10 weeks, 30%. The corresponding DI for each infusion duration was (1) 24 hours, 2.6 g/m2/week; (2) 48 hours, 2.4 g/m2/week; (3) 120 hours, 1.25 g/m2/week; (4) 14-days, 1.225 g/m2/week; and (5) 10 weeks, 2.1 g/m2/week. Cost analysis by actual reimbursement was compared for 5-FU infusion and bolus 5-FU with leucovorin (high and low dose) and 5-FU with interferon. Monthly reimbursement for each is $1400, $2000, and $1150, and up to $3000, respectively. CONCLUSIONS: DI and infusion duration have a complex interaction that may contribute meaningfully to the therapeutic index, but this issue can only be resolved by randomized clinical trials. The cost of 5 FU infusion is comparable to that of bolus therapy when leucovorin or interferon are added in combination. Considering the relative absence of patient toxicity, the costs of 5-FU infusion are substantially less than bolus delivery. PMID- 1638470 TI - Treatment of the patient with cancer using parenteral electronic drug administration. AB - Oncologic therapy demands technologic sophistication to meet the clinical challenges of proper drug administration for chemotherapeutic agents, pain management, antibiotics, hydration, antiemetic drugs, and total parenteral nutrition. Drug administration systems for patient-controlled analgesia include benefits of improved pain control, minimal adverse reactions, lower doses compared with conventional therapy, a high degree of patient acceptance, reduced labor costs, and achievable home therapy. System advances have made epidural, intrathecal, intravenous with bolus capability, and regional or implantable administration possible. In chemotherapy, protracted drug infusions and considerations of circadian rhythms, sequences, and cytostatic treatment will be enhanced further by automated programmable pumps that can meet the challenges of complex protocols. Multidrug antibiotic treatments also are a reality. Electronic drug administration will continue to meet the challenges of site-specific agents and complex dosing regimens to provide therapy for the patient with cancer to achieve an efficacious safe acceptable efficient cost-benefit ratio. PMID- 1638472 TI - Familial occurrence of multiple nonmelanoma skin cancer. AB - A survey of patients with histologically confirmed nonmelanoma skin cancer (NMSC) found 12 families in which several members developed skin cancers. The prevalence of NMSC in these families was far greater than in the normal population. The trait appeared to be dominantly inherited, and NMSC developed at an earlier age in succeeding generations, possibly because of a change in sun exposure habits. PMID- 1638474 TI - Translocation (6;8)(q22;q12) in Ph+ chronic myelocytic leukemia. PMID- 1638473 TI - Structural rearrangement of the Y chromosome in a case of acute myeloid leukemia M2. AB - Involvement of the Y chromosome in numerical changes associated with acute nonlymphocytic leukemia is quite common, whereas acquired structural rearrangements of the Y chromosome are much rarer, there being only four such cases documented in the literature [1]. We identified a case of acute myeloid leukemia (AML M2) with rearrangements of chromosomes 1, 10, and Y; at remission, all analyzed metaphases were normal, confirming the acquired nature of the Y chromosome abnormality. PMID- 1638475 TI - Non-random involvement of chromosome 5 in ALL. PMID- 1638477 TI - Prognostic impact of karyotype and immunologic phenotype in 125 adult patients with de novo AML. AB - One hundred-twenty-five adult patients with de novo acute myeloid leukemia (AML) were treated according to a standard 7 + 3 induction regimen. Karyotype and immunological phenotype of blasts examined prior to treatment were correlated with each other, with response to treatment and duration of survival. The following monoclonal antibodies (mAbs) were used for immunological phenotyping: VIM-D5 (CD15), MY7 (CD13), MY9 (CD33), VIM-2 (CDw65), VIM-13 (CD14), 63D3 (CD14), VID-1 (anti HLA-DR), WT1 (CD7), CLB-Ery3 (antiblood group H antigen), C17-27 (CD61), and an antiserum against TdT. Despite a considerable overlap between the individual groups, patients with specific aberrations as defined by the MIC classification (n = 39) showed distinct, characteristic, myeloid or myelomonocytic immunophenotypes. In M2/t(8;21) there was a significant association with negativity to CD13, in M3/t(15;17) with negativity to CD15 and HLA-DR, whereas in M4/inv(16) expression of blood group H antigen was unexpectedly found. The response to therapy, as well as rate of complete remission as duration of survival, was better in patients with M2/t(8;21), M3/t(15;17), and M4Eo/inv(16) as compared to all other patients and significantly worse in patients with M5a/t/del(11)(q23). In 35 patients with normal karyotype and 16 patients with cytogenetic anomalies not presently associated with FAB subtypes the expected correlations of rather immature myeloid immunologic phenotypes with M1 and M2 morphology and CD14 expression in monoblastic leukemias was found. Remission rate and survival were significantly worse in 19 patients with complex nonrandom aberrations, where blast cell expression of blood group H antigen and of TdT were significantly increased. PMID- 1638476 TI - -Y,-1 as recurrent anomaly in oncocytoma. PMID- 1638478 TI - Cytogenetic analysis of a United Kingdom series of non-Hodgkins lymphomas. AB - We describe cytogenetic analyses of cells derived from 40 non-Hodgkins lymphoma (NHL) node biopsies, 23 of which were from patients who had not been treated before biopsy. We noted that the chromosomes most frequently gained were X (32%), 12 (27%), and 3 (24%). Monosomies were much less common; loss of chromosome 13 (13.5%) was most frequent. Structural abnormalities primarily involved chromosomes 14 (70%), 1 (40.5%), 18 (38%), 6 (35%), and 17 (22%). Low-and high grade disease showed similar patterns of structural changes; however, a markedly greater number of chromosome gains were associated with low-grade disease. Biopsy samples from patients who had previously been treated showed an increased frequency of structural abnormalities, as well as a significantly larger number of chromosome gains. The importance of these observations, particularly with regard to possible oncogene involvement in lymphoma evolution, is discussed. PMID- 1638479 TI - Loss of Y chromosome in gastric carcinoma. Fact or artifact? AB - Loss of chromosome Y has been reported in gastric cancer cells together with other chromosomal abnormalities. We noted loss of chromosome Y and near-diploid karyotypes in five cases of gastric adenocarcinoma, but DNA flow cytometry performed on fresh tumor tissue showed aneuploid peaks in four of them. Our findings suggest that loss of the Y chromosome in gastric cancer probably reflects the karyotype of a subpopulation of stromal cells and not a neoplasia related chromosomal aberration. PMID- 1638480 TI - Constitutional balanced translocations in patients with solid tumors. AB - In a sample of 329 patients with a solid tumor (colon and breast adenocarcinoma, cervical carcinoma, and meningioma), four balanced constitutional translocations were observed. Two were t(13q14q), and two were reciprocal translocations. Comparison with surveys of newborns showed a significant excess of translocations in our sample. PMID- 1638481 TI - Multiple chromosomal changes and karyotypic evolution in a patient with myelofibrosis. AB - Several subclones were identified in unstimulated peripheral blood cells from a patient with chronic myeloproliferative disease, which was classified as myelofibrosis by morphologic terms. These subclones were characterized by an unusual number of different karyotype anomalies. Some of the more complex chromosomal rearrangements could be clearly defined by fluorescence in situ hybridization. Chromosome arms involved in clonal aberrations were 1q, 3p, 6p, 7q, 11q, 13q, 15q, 17q, 18p, and 20q. Reconstruction of karyotype evolution was attempted by karyotypic analysis of 100 metaphase spreads each in two separate investigations. PMID- 1638482 TI - Cytogenetic analysis of six renal oncocytomas and a chromophobe cell renal carcinoma. Evidence that -Y, -1 may be a characteristic anomaly in renal oncocytomas. AB - Renal oncocytomas are benign tumors whose morphologic features may sometimes be confused with those of certain low-grade malignant neoplasms of the kidney, e.g., chromophobe cell and granular cell variants of renal carcinoma. The presence of a specific genetic abnormality might help differentiate these tumors. Because very few cytogenetic studies of renal oncocytomas have been published, we investigated a consecutive series of six such tumors. We also performed chromosome analysis on a chromophobe cell carcinoma because cytogenetic analyses of this tumor have not been previously reported. Tumor cell metaphases were analyzed after mechanical and enzyme disaggregation, in situ culture, and robotic harvesting. Clonal abnormalities were present in five of the six oncocytomas, and loss of chromosome 1 with loss of the Y chromosome occurred in two. Review of the literature disclosed four other renal oncocytomas with the 44,X,-Y,-1 karyotype. In the chromophobe cell carcinoma, we noted an abnormal clone with a del(11)(p12p15.1); similar anomalies were not observed in the renal oncocytomas. We conclude that renal oncocytomas have clonal chromosome abnormalities and that a subgroup of these tumors may be specifically associated with loss of chromosomes 1 and Y. Because this is a small series, further investigation may help establish whether cytogenetic studies can provide diagnostic and pathogenic information about renal oncocytomas. PMID- 1638483 TI - Cytogenetic analysis of the mature teratoma and the choriocarcinoma component of a testicular mixed nonseminomatous germ cell tumor. AB - We karyotyped two histologically distinct components with different metastatic behavior of a testicular nonseminomatous germ cell tumor. The two components showed an almost identical chromosomal pattern. These almost identical karyotypes of the two components with different metastatic potential suggest that the difference in biologic behavior might result from subtle differences (on microscopic or submicroscopic level) in chromosomal pattern or that these differences are predominantly epigenetically determined and depend primarily on the lineage of differentiation of the tumor component. Trophoblastic differentiation results in an aggressive, angioinvasive tumor but in development of teratoma in a tumor with low malignant potential. PMID- 1638484 TI - Fibroblast cultures of patients with basal cell epithelioma exhibit a normal sensitivity to the genotoxic effect of ultraviolet irradiation. AB - Fibroblast cultures of 16 basal cell epithelioma (basalioma, BCE) patients with an unusually young age at onset of disease (29-51 years; 42.5 +/- 7.04), and healthy normal controls (27-55 years; 40.73 +/- 9.52) were studied for chromosome instability induced by ultraviolet rays (UV). We used an UV source that emitted predominantly UV-A and UV-B at an intensity of 375 J/m2 and evaluated the induction of micronuclei (MN) and sister chromatid exchange (SCE). Young basalioma patients and normal controls showed no significant differences in MN and SCE frequencies, neither with respect to spontaneous nor to UV-induced values (MN spontaneous: 10.80 +/- 5.65 vs. 11.32 +/- 8.21; UV-induced increase: 7.36 +/- 4.40 vs. 9.93 +/- 7.55; SCE spontaneous: 10.28 +/- 1.61 vs. 10.72 +/- 1.09; UV induced increase: 7.30 +/- 2.19 vs. 7.55 +/- 2.14). We conclude from these data that an enhanced UV sensitivity as observed in cells from patients with cutaneous malignant melanoma and xeroderma pigmentosum is not a constitutive risk factor in basalioma patients. PMID- 1638485 TI - Establishment and characterization of four Sinclair swine cutaneous malignant melanoma cell lines. AB - Cutaneous malignant melanoma of Sinclair Swine (SSCM) is a heritable, congenital neoplasm which either proves fatal to the neonatal animal or undergoes spontaneous regression. Four SSCM cell lines, UISO-SSCM-433, UISO-SSCM-438, UISO SSCM-5052, and UISO-SSCM-8093, were derived from biopsy specimens of primary tumors removed from swine at 26, 8, and 8 weeks of age, and 15 weeks gestation, respectively. Morphologic features, DOPA oxidase staining, and abnormal karyotype were suggestive of malignant melanoma. Each cell line was morphologically heterogeneous in culture with dendritic, spindle- and cuboidal-shaped cells. Pigmented melanosomes and DOPA oxidase activity were present in all cell lines at passages 20-22. UISO-SSCM-433 and UISO-SSCM-5052 contained hypodiploid and hypotetraploid sublines whereas UISO-SSCM-438 and UISO-SSCM-8093 were hypodiploid and hypotetraploid, respectively. At later passages, all cell lines presented evolutionary, karyotypic changes; the same chromosomes were involved in the alterations, however. Chromosomes 2, 6, 13, and 14 were the most affected, exhibiting numerical and structural alterations in all four cell lines. Despite the presence of multiple chromosomal anomalies in all cell lines, each with a unique set of chromosomal markers, clonal growth was not detected in soft agar, nor were any of the lines tumorigenic following s.c. inoculation in athymic mice. This suggests that the loss of malignant potential in SSCM may be inherent. PMID- 1638486 TI - Deletion of the long arm of chromosome 5 in essential thrombocythemia. AB - A 51-year-old woman with no history of prior chemotherapy or radiation therapy was diagnosed with essential thrombocythemia (ET) according to the diagnostic criteria established by the Polycythemia Vera Study Group (PVSG). Cytogenetic analysis of bone marrow metaphases revealed both normal female karyotype and a single clonal abnormality, 46,XX,del(5)(q22q35). While chromosomal abnormalities have been reported in ET, their incidence is very low, and no specific abnormality has been found. Many of the reported cases of ET with chromosomal aberrations, including 5q-, do not meet the diagnostic criteria proposed by the PVSG, and may represent one of the other myeloproliferative disorders or a myelodysplastic syndrome. Furthermore, it is important to distinguish the 5q- syndrome, which may present with thrombocytosis and megakaryocytic hyperplasia, from ET. Our patient appears to be the first example of untreated ET clearly meeting the PVSG criteria in which 5q- was the only clonal abnormality seen at diagnosis. PMID- 1638487 TI - Cytogenetic studies of an adrenal cortical carcinoma. AB - Cytogenetic findings in the third reported case of adrenal cortical carcinoma are described. In contrast to the two previous cases, hypodiploidy characterized almost all cells, which had as many as eight abnormal chromosomes in each cell analyzed. PMID- 1638489 TI - Monosomy 21 in two patients with acute nonlymphocytic leukemia. AB - Among 50 cases of acute nonlymphocytic leukemia (ANLL) with available cytogenetic data seen in our section since May 1988, two were found to carry a monosomy 21 abnormality which has been rarely reported in hematologic malignancies. The first case is a 58-year-old male with a diagnosis of AML, FAB M2, who died of refractory leukemia 9 months later. The other case is a 59-year-old female with AML, FAB M2. Complete remission was achieved initially but she died of sepsis 3 months later with no evidence of leukemic relapse. Monosomy 21 is not yet recognized as a nonrandom cytogenetic abnormality in ANLL, whereas its unusual predilection in AML, especially the FAB M2 or M4 categories, as noted in our study and others' reports, have raised this possibility. Further studies and the accumulation of new cases are needed in the hope of defining it as a subtype of ANLL. PMID- 1638488 TI - Acute monoblastic leukemia of infancy in Klinefelter's syndrome. AB - A 7-month-old infant with Klinefelter's syndrome was diagnosed as having acute monoblastic leukemia (AMoL). Chromosome studies of bone marrow at diagnosis showed the karyotype 46,XXY,-Y,t(10;11)(p13;q14). This is the first report of M5A leukemia associated with Klinefelter's syndrome. PMID- 1638490 TI - The use of giant cell tumor conditioned media in cytogenetic studies of hematologic malignancies. AB - The use of conditioned media produced from solid tumor cell lines has been beneficial in the study of hematologic malignancies. Conditioned media from giant cell tumors (GCT), human lung adenocarcinoma, and human bladder carcinoma express growth factors that have been used to stimulate growth of bone marrow cells and improve the quality of the preparations. It has been reported that addition of Lu CSF1-conditioned media from a lung adenocarcinoma cell line masks abnormalities in cases of acute leukemia [1.] Because we routinely use GCT-CM in bone marrow and leukemic blood cultures for chromosome analysis in our lab, we investigated this potential effect on our case analysis. We have performed a serial study of a 100 cases of hematologic malignancies received for analysis in our lab to determine the effect of the addition of GCT-CM to our culture media with respect to 1) mitotic index, 2) quality of preparation, and 3) differential selection of either chromosomally normal or abnormal cell lines. Our results indicate that the mitotic index and quality of metaphases is enhanced with the addition of GCT media and that there is no difference in the rate of abnormality detection with or without the addition of GCT media. PMID- 1638491 TI - Inversion (X)(p22q13) in a uterine leiomyoma. AB - We report a case of uterine leiomyoma which showed a karyotype 46,X,inv(X)(p22q13) as the only clonal change in most of the cells. A few cells had an additional del(7), though del(7) has been found to be a primary change in leiomyomas. These findings indicate that the abnormality involving the X chromosome and particularly Xp22 can be considered as a primary chromosomal abnormality. We discuss the findings together with few reports of cases involving chromosome X in leiomyomas. PMID- 1638492 TI - Analysis of a giant marker chromosome in a well-differentiated liposarcoma using cytogenetics and fluorescence in situ hybridization. AB - Well-differentiated liposarcomas (LPS) are cytogenetically very complex, characterized by giant marker chromosomes, ring chromosomes, and telomeric associations. We report a case of well-differentiated LPS in which the only cytogenetic anomaly was an additional giant marker. In an attempt to identify the origin of this marker, centromeric probes (chosen on the basis of the morphology of the marker) to chromosomes 1,2,3,4,6,7,8,9,10,11,12,16,17, and X and a shared satellite probe for chromosomes 1,5, and 19, were used with fluorescence in situ hybridization (FISH). This was successful at eliminating certain chromosomes as candidates for centromeric trisomy but could not identify the origin of the marker. This case is unusual in that it does not conform to the typical cytogenetic pattern for well-differentiated LPS and is the first known example with an apparently normal diploid karyotype with only one additional change. PMID- 1638493 TI - AML with unusual chromosomal changes. Translocation (15;21) and 5q- in the presence of two normal chromosomes 5. AB - We performed serial cytogenetic studies of the bone marrow (BM) of a patient with acute myeloblastic leukemia (AML) and noted abnormal karyotypes 47,XY,+del(5)(q12q34),t(15;21)(q21;q22)/47,XY,+del(5)(q12q34 ) during the second relapse. Although a case of this t(15;21) was recently observed in a female patient with acute nonlymphocytic leukemia (ANLL) of subtype M4 of the French American-British (FAB) classification, the present article constitutes the first report of its occurrence in association with ANLL of subtype M1-M2. Furthermore, the presence of the 5q- accompanied by two chromosomes 5 of normal appearance is very rare and of great interest. PMID- 1638494 TI - Sister chromatid exchange frequency in breast cancer cases. AB - Sister chromatid exchange (SCE) were studied in 22 patients with breast cancer (i.e., four stage II; 12 stage III, six stage IV) and 10 normal healthy females as age-matched controls. The data obtained in these cases followed a Poisson distribution. An apparent increase in the average rate of SCE/cell was observed with the advancing stage of breast cancer. PMID- 1638495 TI - Chromosomal abnormalities in Waldenstrom's macroglobulinemia. AB - We report the results of cytogenetic studies of direct bone marrow (BM) preparations and of short-term BM and peripheral blood (PB) cultures from 17 patients with Waldenstrom's macroglobulinemia. We noted clonal chromosome changes in 10 patients. Abnormalities affected chromosomes X, Y, 2, 4, 5, 15, 16, 18, 19, 20, 21, and 22; in particular, chromosomes 2, 4, and 5 were involved in structural changes: a homogeneously staining region [hsr(2)], a der(4)t(4;?)(q32;?), and a 5q+. The other chromosomes were involved in numerical abnormalities, such as pseudodiploidy (a 46,X, -X, + 15 clone), loss of chromosome Y, and monosomy of chromosomes 16, 18, 19, 20, 21, and 22. Nonclonal chromosome rearrangements were also observed. The results are discussed in comparison with the few data reported in the literature, and the finding of an hsr in the long arm of chromosome 2 is emphasized; indeed, this is the first report of hsr in WM. PMID- 1638496 TI - Graft-versus-leukemia effects after allogeneic bone marrow transplantation are active also in the presence of clones with chromosomal anomalies in addition to the Ph chromosome. AB - Two male patients with Philadelphia-chromosome (Ph+) chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation (ABMT) in the first chronic phase after busulfan treatment. In both cases, the donor was a sister, and engrafting was demonstrated by chromosome analyses which showed only donor cells in the BM. Cytogenetic relapse occurred 29 and 30 months after ABMT, respectively, when host cells reappeared: in both cases, the Ph and additional anomalies typical of the blastic phase of CML were evident. We then monitored the chromosome picture for 52 and 39 months, respectively: no striking evolution occurred, and cells with the Ph and additional anomalies persisted together with donor cells, which were a minority in the first patient and a great majority in the second throughout the observation period. A clinical relapse was observed in the first patient, but the disease never progressed to a blastic phase, whereas the second patient has not relapsed 7 years after ABMT. We reviewed data from the literature on cytogenetic relapse after ABMT in CML without clinical relapse, especially the 12 patients in whom cytogenetic relapse included chromosome anomalies in addition to the Ph, as in our patients. We suggest that graft-versus leukemia (GVL) reactions in such patients are able to arrest progression of the leukemic blastic clone and prevent a possible relapse in blastic phase. PMID- 1638497 TI - Multiple unrelated chromosome abnormalities in a metastatic mucoepidermoid carcinoma of the parotid gland. AB - We describe cytogenetic findings in a poorly differentiated, metastatic mucoepidermoid carcinoma of the parotid gland. The tumor was characterized by multiple, unrelated chromosome abnormalities. Except for two small aberrant clones showing t(1;7) and t(2;15), respectively, all other abnormal cells showed unique, mostly structural rearrangements peculiar to each cell. No less than 34 different abnormal karyotypes were observed. A similar karyotypic heterogeneity was also described recently in squamous cell carcinomas of the head and neck. PMID- 1638498 TI - Leukemic evolution in three patients with myelodysplastic syndrome and unusual chromosome changes. AB - The authors describe three patients with myelodysplastic syndrome without a history of exposure to chemical agents and who showed many chromosome rearrangements not previously reported in this hematologic disorder, and a rapid outcome of the disease. The authors discuss the significance of the chromosome changes, suggesting, in agreement with others, that patients with complex rearrangements have a poor prognosis. PMID- 1638499 TI - Cytogenetics of primary prostatic adenocarcinoma. Clonality and chromosome instability. AB - We have examined 62 prostatic adenocarcinomas by conventional cytogenetic analysis. Most were primary cultures harvested in 14 days or less. The most consistent finding was a normal male diploid karyotype, found in 87% of all cells analyzed, and as the exclusive finding in 19 tumors. Nonrandom chromosomal changes included gain of chromosome 7 and loss of the Y chromosome. In addition, clonal gains of chromosomes 8, 12, and 18, and clonal losses of chromosomes 14 and 19 were noted in individual cases. Two structural clonal aberrations, a 9p+ in one case and a t(Y;22) (q11.2;p12) in another, were also seen. Ten of 62 cultures demonstrated chromosome instability, defined herein as nonclonal gain or loss of chromosomes in more than 10% of the metaphases examined from that culture. In those cases with nonclonal numerical aberrations, loss of chromosomes was more common than gain. The distribution of apparently random numeric abnormalities was similar to that of the clonal abnormalities in that the most frequent nonclonal gain was of chromosome 7 and the most frequent nonclonal loss was of the Y chromosome. Apparently random structural aberrations were observed in less than 1% of all analyzed cells. These included a 4p-,del(3)(q13), and t(1;11). The extent of apparently random aneuploidy suggests that chromosome instability characterizes cultured prostatic adenocarcinomas. An increase in the frequency of nonclonal aberrations may be an indicator of tumor origin in a predominantly diploid cell population. The coexistence of clonally aberrant, nonclonally aberrant, and normal diploid cells in culture may reflect heterogeneity of prostate tumors in vivo. PMID- 1638500 TI - Cytohematologic and cytogenetic prognostic factors at diagnosis and in the evolution in 46 primary myelodysplastic syndromes. AB - The myelodysplastic syndromes (MDS) are a heterogeneous group of diseases with different prognosis and evolution. Most of the studies on prognostic factors performed previously have independently evaluated the clinico-hematologic or cytogenetic data at diagnosis. In the present paper, 46 primary MDS were clinically, hematologically, and cytogenetically investigated at diagnosis, in order to determine the principal factors affecting the survival probability between a great number of characteristics. A univariate regression analysis of all the data allows one to recognize that the main factors are: the complexity of karyotype (p = 0.00001), the percentage of type I and total marrow blast cells (p = 0.001), and the abnormal localized immature myeloid precursors' (ALIP) presence (p = 0.001). Twenty-five patients underwent consecutive studies during their evolution. The karyotype instability gives information both on the likely evolution to acute leukemia and on poor survival. PMID- 1638501 TI - Karyotype at relapse following allogeneic bone marrow transplantation for chronic myelogenous leukemia. AB - Eighty-four patients underwent allogeneic or syngeneic bone marrow transplantation as therapy for chronic myelogenous leukemia (CML) during a 5-year period at The Johns Hopkins Oncology Center. We describe the karyotype at relapse in 19 patients who were Ph chromosome positive (Ph+) at diagnosis. Eighty-four percent of patients demonstrated clonal and/or nonclonal chromosome abnormalities in addition to the t(9;22)(q34;q11) at first detection of relapse or later during relapse. These abnormalities included: Ph plus additional clonal abnormalities (three patients), Ph plus nonclonal abnormalities (five patients), Ph plus additional clonal and nonclonal abnormalities (eight patients). Three patients had only the original Ph+ clone. The additional chromosome abnormalities were primarily structural, and entirely different from those most frequently observed during karyotypic evolution in conventionally treated CML. Chromosome 1 was most frequently involved, with 1q32 being the location of three clonal and two nonclonal abnormalities. Other sites included 6p21-22 (the site of two clonal abnormalities), 7p21-22, and 10q21 (the site of two clonal and one nonclonal abnormality each). Chromosomes 5 and 7q, regions of frequent involvement in acute nonlymphocytic leukemia that follows chemotherapy for other malignancies, were infrequently involved. The clinical significance of these additional abnormalities remains undetermined at this time. PMID- 1638502 TI - Cytogenetic evidence for a chromosome 22 tumor suppressor gene in ependymoma. AB - Although ependymomas comprise 5-10% of pediatric brain tumors, consistent cytogenetic aberrations have not been identified in these neoplasms. We report karyotypes for two ependymomas. A predominantly well-differentiated ependymoma contained several numerical chromosome aberrations, including monosomy 22. In contrast, an anaplastic ependymoma had a more complex karyotype that included loss of one chromosome 22 homologue and a balanced translocation at q13.3 in the remaining 22 homologue. These findings suggest the location of an ependymoma tumor suppressor gene on the long arm of chromosome 22. PMID- 1638503 TI - Inversion of chromosome 16 and bone marrow eosinophilia in a myelomonocytic transformation of chronic myeloid leukemia. AB - We report a case of chronic myeloid leukemia (CML) in myelomonocytic transformation associated with bone marrow (BM) eosinophilia. At diagnosis, all BM cells showed a Ph chromosome. At the time of blastic phase, more than 50% of Ph+ cells had a pericentric inversion of chromosome 16, inv(16)(p13q22). This case confirms that blastic transformation of CML can involve any committed progenitor, and myelomonocytic leukemia with BM eosinophilia is specifically associated with rearrangement of chromosome 16 at band p13 and q22. PMID- 1638504 TI - 5q- anomaly in acute lymphoblastic leukemia. AB - We report two new cases of common acute lymphoblastic leukemia (ALL) with 5q-. This abnormality, which is uncommon in ALL, was previously reported in 14 cases of ALL of various subtypes and appears to occur less frequently in common ALL than in other types of ALL. PMID- 1638505 TI - Significant telomere shortening in childhood leukemia. AB - Telomere length was studied by Southern analysis in five cases of childhood acute leukemia. In four cases, the length of the telomere sequence of the blast phase cells was shortened as compared with that of the cells examined during remission. Study of telomere length during chemotherapy for hematologic malignancies may show rapidly dividing subpopulations of malignant cells and thereby guide further treatment needs. In addition, such loss of telomere sequence would give rise to chromosomal instability and could be one of the mechanisms of oncogene activation in acute leukemia. PMID- 1638506 TI - Cytogenetic analysis of a juvenile granulosa cell tumor. AB - We report chromosomal changes in a juvenile granulosa cell tumor with complex chromosomal rearrangements. These tumors have not been subjected previously to cytogenetic analysis. PMID- 1638508 TI - Relationship between fragile sites and cancer breakpoints. PMID- 1638507 TI - Loss of chromosome 22 in patients with refractory anemia with excess of blasts (RAEB) in transformation and acute leukemia after RAEB. AB - We report studies of 12 patients with refractory anemia and excess of blasts in transformation (RAEB-t) and 17 with acute myeloblastic leukemia (AML) after RAEB. Besides chromosome 5 and 7 abnormalities, five patients with complex karyotypic changes had monosomy 22. This association is discussed in relation to the hypothesis of a suppressor gene located on chromosome 22. PMID- 1638509 TI - A case of trisomy 5 in a Philadelphia positive leukemia. PMID- 1638510 TI - Duplication of the der(14) chromosome of a translocation (8;14) in a case of Burkitt's type L3-ALL. PMID- 1638512 TI - Effects of inositol hexaphosphate on growth and differentiation in K-562 erythroleukemia cell line. AB - Inositol hexaphosphate (InsP6) has recently been shown to inhibit experimental cancers in vivo. Since the lower phosphorylated forms of InsP6 are important in cell growth in a wide variety of mammalian cells, we tested the efficacy of InsP6 in growth reduction of K-562 human erythroleukemia cells in vitro. We report that InsP6 decreases the K-562 cell population by 19-36% (P less than 0.001) concomitant to an increased differentiation as evidenced by ultrastructural morphology and increased hemoglobin synthesis. Pilot experiments to study the mechanism of action of InsP6 show that following treatment with InsP6, the concentration of intracellular [Ca2+] ([Ca2+]i) is increased by 57% (P less than 0.02). Likewise, a 41% increase (P less than 0.05) in InsP3 and a 26% decrease (P less than 0.02) in InsP2 were noted 1 h following treatment with InsP6. Contrary to the dogma that cell division is associated with increased [Ca2+]i, our data show that reduced cell growth and enhanced differentiation is associated with increased [Ca2+]i and increased InsP3 in the presence of InsP6. PMID- 1638511 TI - Differential stimulation of macrophages for tumor cytostasis and monokine production. AB - We have investigated whether antitumor activity could be expressed independently of cytokine production. Resident macrophages treated with interferon-gamma (IFN gamma), lipopolysaccharide (LPS) plus muramyldipeptide (MDP) expressed a cytostatic activity against P815 tumor cells and released interleukin 6 (IL-6) and nitrite but produced neither IL-1 nor tumor necrosis factor (TNF). Thioglycollate-elicited macrophages required only LPS plus IFN-gamma for cytostatic activity which was expressed concomitantly with the release of high levels of TNF, IL-1 and IL-6, whereas C3H/HeJ macrophages produced low levels of monokines and were not cytostatic. LPS, alone, was sufficient for triggering Concanavalin A-primed macrophages leading to a full cytostatic activity, even in C3H/HeJ macrophages that was expressed, for these latter, in the absence of monokine production. TNF did not appear to play a role either in autocrine stimulation of macrophages or in the cytostatic process because anti-TNF antiserum affected neither the cytostatic activity nor the nitrite production. PMID- 1638513 TI - The control by estradiol of pituitary tumor and cell growth is not correlated with that of kallikrein gene expression. AB - From an MtTF4 pituitary tumor we established new cell lines and tumors whose growth is sensitive (stimulation or inhibition) or insensitive to estradiol (Cancer Res., 1991, 50, 3786-3794). The main objective of the present work was to determine whether such a diversity of responses is correlated with the estradiol control of kallikrein gene expression. From kallikrein mRNA analyses and from kallikrein activity assays in conditioned medium it appears highly probable that the diversity of responses to estradiol of pituitary tumors and cell growth is not due to a differential regulation of kallikrein gene expression. In addition, prolactin gene expression and estrogen receptor mRNA have been studied to further characterize this experimental model. PMID- 1638514 TI - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH, E.C. 1.2.1.12.) gene expression in two malignant human mammary epithelial cell lines: BT-20 and MCF-7. Regulation of gene expression by 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). AB - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key enzyme in the control of glycolysis. Its gene expression was analyzed in two breast cancer cell lines of human origin, BT-20 and MCF-7. We used a cDNA probe of 1.3 kb for Northern blot hybridization. It is found that GAPDH mRNA is overexpressed only in the poorly differentiated BT-20 cell line and that treatment of these cells by 1,25 dihydroxyvitamin D3 (1,25-(OH)2D3) stimulates GAPDH mRNA expression in a dose-and time-dependent manner. The present investigation on the BT-20 cells indicates that the expression of GAPDH is sensitive to 1,25-(OH)2D3 and up-regulated by low doses of this steroid. PMID- 1638515 TI - Glutathione conjugation of microsome-mediated and synthetic aflatoxin B1-8,9 oxide by purified glutathione S-transferases from rats. AB - Glutathione (GSH) conjugation of microsome-mediated and synthetic aflatoxin B1 (AFB1)-epoxide and styrene oxide has been investigated with purified GSH S transferases (GSTs) from rats. Both styrene oxide and AFB1-epoxide were conjugated preferentially by millimicrons GSTs 3-3, 3-4 and 4-4 as compared to alpha GSTs 1-1, 1-2 and 2-2. The highest catalytic activity with styrene oxide conjugation was associated with GST 4-4. The highest catalytic activity with microsome-mediated AFB1-epoxide conjugation was observed with GST 3-3 whereas with the synthetic AFB1-epoxide conjugation was seen with GST 4-4. The catalytic activity of pi GST 7-7 was intermediate to millimicrons and alpha GSTs. It is suggested that GST 3-3 may play an important role in inactivation of AFB1-epoxide generated in vivo in the rat. PMID- 1638516 TI - Characterization of potentially mutagenic products from the nitrosation of piperine. AB - Piperine is the main pungent principle of pepper, a spice consumed by people all over the world. It is the trans-trans isomer of 1-piperoylpiperidine and contains the methylene dioxy moiety. It is known to give unidentified mutagenic products on reaction with nitrite. The nitrosation reaction of piperine is of concern as endogenous nitrosation could take place in the human stomach from ingested precursors, piperine and nitrite. Nitrites can be ingested directly by consuming cured foods or indirectly as nitrates, which could be converted to nitrites under appropriate conditions. We have nitrosated piperine using aqueous nitrous acid and have isolated and identified some N-nitroso and C-nitro compounds. Their isolation, characterization and potential mutagenicity has been discussed. PMID- 1638517 TI - The growth inhibitory action of melatonin on human breast cancer cells is linked to the estrogen response system. AB - The pineal hormone, melatonin, was examined for its capacity to modulate the proliferation of a panel of human breast cancer cell lines. Melatonin inhibited, to a varying extent, the proliferation of all three estrogen-responsive cell lines, but had no effect on estrogen-insensitive breast tumor cell lines. Melatonin was also able to specifically block estrogen-induced proliferation in MCF-7 breast cancer cells. However, this action was abolished in the presence of tamoxifen. Therefore, it appears that the antiproliferative effects of melatonin are mediated through the estrogen-response pathway. PMID- 1638518 TI - Azidothymidine-induced cytotoxicity and incorporation into DNA in the human colon tumor cell line HCT-8 is enhanced by methotrexate in vitro and in vivo. AB - We have reported that 5-fluorouracil can increase the cytotoxic and antineoplastic activity of 3'-azido-3'-deoxythymidine (AZT). To further evaluate the antineoplastic utility of AZT we now have assessed its effect in combination with methotrexate (MTX) in the human colon tumor model HCT-8. Incubation of these cells for 5 days in AZT and MTX caused a reduction in the 50% inhibitory concentration of AZT and isobologram analysis revealed additive effects which were reversed by the addition of 50 microM thymidine to the incubation media. This enhanced cytotoxicity appeared not to be related to an effect of AZT on MTX activity; in whole-cell assays the ability of MTX to inhibit de novo dTMP synthesis and deplete intracellular pools of dTTP was not affected by AZT. In contrast, although MTX did not alter AZT triphosphate production, it did affect AZT triphosphate utilization in DNA synthesis. Incubation of cells for 24 h in [3H]AZT alone (5 microM, 3 microCi/ml) resulted in 6.6 pmol AZT incorporated into cellular DNA/10(6) cells. Coincubation of these cells in [3H]AZT (5 microM) plus 5 or 15 nM MTX increased AZT incorporation into DNA to 8.0 and 20.5 pmol/10(6) cells, respectively. Biochemically, this effect appeared to correlate with the concentration-dependent ability of 5 or 15 nM MTX to deplete intracellular dTTP pools, which were reduced by 25 and 49%, respectively. Further evidence of the relationship between intracellular dTTP pools and AZT cytotoxicity was that, in the presence of both MTX and 50 microM thymidine, intracellular dTTP pools remained near normal levels and the incorporation of 5 microM AZT into DNA was not enhanced. Therapeutically, studies conducted in athymic (nude) mice bearing HCT-8 xenografts that received six weekly cycles of MTX (87.5 mg/kg) and AZT (300 mg/kg) revealed that the two-drug regimen exerted superior antineoplastic effects compared to either drug alone (treated versus control approximately 0.9 for AZT or MTX and approximately 0.3 for MTX plus AZT). In addition, the combination did not increase toxicity compared to therapy with MTX alone. These findings are discussed in light of their biochemical and clinical implications. PMID- 1638519 TI - Prevention of acute chemotherapy-induced death in mice by recombinant human interleukin 1: protection from hematological and nonhematological toxicities. AB - Previous studies have demonstrated that interleukin 1 (IL-1) can protect most mice from the acute lethal toxicity mediated by high doses of radiation and/or some chemotherapeutic drugs. The results presented herein demonstrate that the pretreatment of mice with recombinant human interleukin 1 alpha (rhIL-1 alpha) protects mice from the lethal effects of several myelotoxic chemotherapeutic drugs, including 5-fluorouracil (5FUra), cyclophosphamide, cis-diammine(1,1 cyclobutanedicarboxylato)platinum(II), and 1,3-bis-(2-chloroethyl)-1-nitrosourea. However, pretreatment with rhIL-1 alpha was not effective against the acute lethal toxicity generated by doxorubicin and cisplatin. The chemoprotective effects appear to be at least partially due to myeloprotection/restoration, since the recovery of myeloid colony-forming units and the total cellularity in the bone marrow and spleen were accelerated in the rhIL-1 alpha-pretreated mice. However, the chemoprotective effects of rhIL-1 alpha are apparently not limited to myeloprotection, since pretreatment with rhIL-1 alpha protects mice against the lethal toxicity of both 5FUra and cyclophosphamide, yet bone marrow transplants rescue mice treated with 5FUra but not those treated with cyclophosphamide. The chemoprotective effects of rhIL-1 alpha may be at least partially indirect, since the efficacy of chemoprotection by rhIL-1 alpha is reduced in athymic mice, and interleukin 6, but not tumor necrosis factor alpha, can substitute for rhIL-1 alpha in chemoprotection from 5FUra. PMID- 1638520 TI - Multiparameter assessment of the cell cycle effects of bioactive and cytotoxic agents. AB - This paper describes the use of the bromodeoxyuridine/propidium iodide method to assess the effects of bioactive and cytotoxic agents on the kinetic characteristics of acute myelogenous leukemia cells. By careful selection of gates, the following parameters can be measured simultaneously using only 50,000 cells: the proportion of cells in S-phase, the distribution of cells within the S phase compartment, the relative rate of DNA synthesis, the relative distribution of S-phase times, the proportion of S0 cells, and the proportion of cells in G1 and G2/M. This method was used to demonstrate that while retinoic acid, alpha interferon, and cytosine arabinoside may all "inhibit" DNA synthesis, the actual effects of these agents differ. Retinoic acid appears to arrest cells in G1 without affecting the rate of DNA synthesis, while alpha-interferon and cytosine arabinoside "inhibit" DNA synthesis by reducing the rate of synthesis per se. PMID- 1638521 TI - Increased therapeutic efficacy induced by tumor necrosis factor alpha combined with platinum complexes and whole-body hyperthermia in rats. AB - This study examined the effect of a trimodality therapy of the combination of recombinant human tumor necrosis factor alpha (TNF), whole-body hypertheria (WBH), and cis-diamminedichloroplatinum(II) (CDDP) or cis-diammine-1,1 cyclobutane dicarboxylate platinum(II) (CBDCA) on a fibrosarcoma and normal tissue in F344 rats. TNF (1 x 10(5) units/kg) increased the antitumor effect of both CDDP (1.5 mg/kg) + WBH (2 h at 41.5 degrees C) and CBDCA (30 mg/kg) + WBH. Tumor growth delay, which was 1.9 days for CDDP + WBH and 2.7 days for CBDCA + WBH (P less than 0.01 compared to control), was significantly increased to 2.9 days with TNF + CDDP + WBH and 5.4 days with TNF + CBDCA + WBH (P less than 0.05). WBH, TNF, CDDP or CBDCA alone, TNF + CDDP, TNF + CBDCA, or TNF + WBH had no significant effect on tumor growth. In contrast, administration of TNF did not enhance the CDDP- or CBDCA-mediated dose limiting normal tissue toxicity. CDDP + WBH-mediated acute renal injury and CBDCA + WBH-mediated acute myelosuppression, as determined by blood urea nitrogen and peripheral blood cell counts, respectively, were not increased with the addition of TNF to either dual modality therapy. Histopathologically, addition of TNF produced no significant alterations in the kidney and the bone marrow as compared to CDDP + WBH or CBDCA + WBH. These data show that TNF enhanced the platinum + WBH-mediated antitumor effect without increasing normal tissue toxicity, suggesting that TNF may increase the therapeutic efficacy of CDDP or CBDCA combined with WBH. PMID- 1638522 TI - Resistance to tamoxifen with persisting sensitivity to estrogen: possible mediation by excessive antiestrogen binding site activity. AB - The growth of a large proportion of estrogen receptor-positive breast tumors is stimulated by estrogen and can often be controlled through antiestrogen therapy. Resistance to antiestrogen (AE) therapy can occur while tumors retain the expression of estrogen receptors (ERc) and remain functionally responsive to estrogens. The ability of specific antiestrogen binding sites (AEBS) to prevent AE from interacting with ERc has been examined as a possible mechanism through which this appropriation of AE could interfere with antiestrogen action. Comparisons were performed between uterine preparations where ERc activity exceeded AEBS binding and liver preparations where AEBS binding predominated. Identical estimates of ERc activity were obtained in uterine preparations using either [3H]estradiol or [3H]-4OH-tamoxifen and radioinert diethylstilbestrol (alpha,alpha'-diethyl-4,4'-stilbenediol) to estimate nonspecific binding. AEBS binding was observed only when [3H]-4OH-tamoxifen was used, while binding to Type II sites was resolved only with [3H]estradiol. When excess AEBS activity predominated, analyses with radiolabeled estrogen and antiestrogen present simultaneously showed that virtually all of the antagonist was bound to AEBS with little of the antagonist available to associate with ERc. In an effort to relate these observations to AE resistance per se, ERc and AEBS were measured in MCF-7 human breast cancer cells (ERc-positive, responsive to estrogens and antiestrogens) and in variant AE-insensitive LY-2 human breast cancer cells (ERc positive, responsive only to estrogens). In AE-resistant LY-2 cells, the ratio of AEBS:ERc was approximately three times greater than in MCF-7 cells. Examination of 128 human breast carcinomas revealed that AEBS activity was present and could exceed ERc activity. Importantly, the partition of significant AE away from ERc was observed in human specimens. These observations identify a biochemical mechanism for antiestrogen resistance through which AE access to ERc can be totally incapacitated while sensitivity to estrogens continues. These observations indicate that AEBS activity, in addition to ERc activity, may provide helpful information for predicting the response of certain cancers to hormonal therapy. PMID- 1638523 TI - Interleukin 6 reduces lipoprotein lipase activity in adipose tissue of mice in vivo and in 3T3-L1 adipocytes: a possible role for interleukin 6 in cancer cachexia. AB - To investigate whether interleukin 6 (IL-6) might be a potential mediator of the depleted fat reserves observed in malignancy-associated cachexia, we measured lipoprotein lipase (LPL) activity in adipose tissue of mice after administration of IL-6 or tumor necrosis factor and in cultured adipocytes after addition of these cytokines. Injection of IL-6 i.p. reduced adipose tissue LPL activity by 53% within 4.5 to 5.5 h. Injection of tumor necrosis factor elevated serum IL-6 levels and reduced adipose tissue LPL activity by 70%. Both human and murine IL-6 reduced heparin-releasable LPL activity in 3T3-L1 adipocytes in a dose-dependent manner; half-maximal inhibition of LPL activity was achieved with 5000 hybridoma growth factor units/ml. Thus, IL-6 reduces adipose LPL activity and may contribute to the loss of body fat stores associated with some cases of cancer cachexia. Since tumor necrosis factor increases circulating IL-6, some of its effects may be mediated or potentiated by IL-6. PMID- 1638524 TI - Tumor resistance induced by syngeneic bone marrow transplantation and enhanced by interleukin 2: a model for the graft versus leukemia reaction. AB - Lethally irradiated C3H/HeN mice reconstituted with normal syngeneic bone marrow survived significantly longer than unmanipulated control mice following challenge with a lethal dose of 38C13 lymphoma cells 2 to 3 weeks post-bone marrow transplantation (BMT). Although the magnitude of this effect was modest, it was highly reproducible. This resistance-producing effect of BMT could be enhanced by interleukin 2 administration and could be abrogated by anti-asialo-GM1 antiserum treatment of recipients. These findings are consistent with the hypothesis that cells with a natural killer phenotype are activated by BMT and can mediate tumor resistance. These studies provide a model to explore the cellular basis, independent of donor alloreactivity, of the graft antitumor effect of BMT observed in humans. PMID- 1638525 TI - Structure-activity study and design of multidrug-resistant reversal compounds by a computer automated structure evaluation methodology. AB - We have studied the relation between the structure and the multidrug resistance reversal activity of a set of diverse chemicals with the MULTICASE structure activity program. A number of key structural features were identified as being related to multidrug resistance reversal activity. Using these key features, we identified seven new compounds predicted to have substantial activity. These were obtained and tested experimentally on a CHO/CHRC5 cell line derived from the AB1 Chinese hamster ovary line in the presence of vincristine and vinblastine. Of the seven compounds tested so far, four showed substantial reversal activity, the most potent of them exhibiting activity at par with verapamil. PMID- 1638526 TI - CI-973, a new platinum derivative with potential antileukemic activity. AB - We examined the effects of CI-973 (supplied by Parke-Davis) on several human leukemia cell lines and a Chinese hamster ovary (CHO) line and their drug resistant counterparts. The cell lines used were HL-60, HL-60/mAMSA, HL-60/DOX, KBM3, KBM3/mAMSA 6, KBM3/mAMSA 6(85), CHO, and CHO/AC-7. DOX, mAMSA, and AC-7 indicate resistance to doxorubicin, amsacrine, or 1-beta-D arabinofuranosylcytosine, respectively. Cells were incubated with CI-973, and the effect was evaluated by two methods: growth inhibition assay and inhibition of colony formation. All cell lines examined were inhibited by CI-973; two of three amsacrine-resistant lines and the one cytarabine-resistant line demonstrated collateral sensitivity. At equivalent dosages, a 4-day exposure provided much greater cell kill than a 1-h exposure. Clonogenic assay showed exponential killing over 3 log units. Maximum CI-973 levels required to kill 50% of cells were 10-fold lower than the peak plasma levels achieved in a phase I solid tumor study. A continuous infusion phase I study in acute leukemia has been initiated. PMID- 1638527 TI - Adriamycin: protection from cell death by removal of extracellular drug. AB - Adriamycin is a cytotoxic drug which has enjoyed considerable success in the treatment of cancer. This agent has a bewildering variety of biological effects both within and on the surface of cells exposed to drug, and it has proved difficult to unambiguously assign a single mechanism of action. In this report we are able to separate intracellular and extracellular actions by taking advantage of the complete lack of Adriamycin-induced cytotoxicity at low temperature. For example, cells exposed to 100 microM Adriamycin at 0 degree C are not killed by the drug, even though this concentration is orders of magnitude higher than the concentration needed to cause 100% cell death at 37 degrees C. If cells exposed to 100 microM Adriamycin at 0 degree C are shifted to fresh drug-free medium at 37 degrees C, there is a time-dependent decrease in survival. However, if the drug-free medium contains calf thymus DNA (1.5 mg/ml) to act as a reservoir for Adriamycin binding of effluxed drug, there is no ensuing cytotoxicity. Thus, the results show that no matter how much drug is present inside the cell, there must also be extracellular drug available for membrane interaction in order to initiate nuclear DNA damage and the cytotoxic cascade. PMID- 1638528 TI - Nitrite and nitrosamine synthesis by hepatocytes isolated from normal woodchucks (Marmota monax) and woodchucks chronically infected with woodchuck hepatitis virus. AB - Hepatocytes isolated from woodchucks (Marmota monax) were shown to produce nitrite in vitro from L-arginine after stimulation with lipopolysaccharide (LPS). Hepatocytes isolated from woodchucks that were chronic carriers of woodchuck hepatitis virus formed twice as much nitrite as hepatocytes from noninfected animals. Nitrite synthesis by hepatocytes was directly related to L-arginine and LPS concentrations in the tissue culture medium and reached a plateau at 0.5 mM L arginine and 1.0 micrograms/ml LPS. LPS-stimulated hepatocytes nitrosated morpholine to form N-nitrosomorpholine in the presence of L-arginine at a physiological pH of 7.4. There was a 10-fold increase in N-nitrosomorpholine production when hepatocytes were stimulated with LPS compared to unstimulated hepatocytes under similar conditions when both nitrite and morpholine were directly added to the medium. NG-monomethyl-L-arginine, a selective inhibitor of nitric oxide synthase, inhibited formation of both nitrite and N nitrosomorpholine. These results demonstrate that nitrosating agents are formed in hepatocytes via the L-arginine-nitric oxide pathway. This suggests that endogenous formation of carcinogenic N-nitroso compounds could influence the process of hepatocarcinogenesis in woodchucks with chronic woodchuck hepatitis virus infection. PMID- 1638529 TI - Inhibition of hematopoietic tumor growth by combined treatment with deferoxamine and an IgG monoclonal antibody against the transferrin receptor: evidence for a threshold model of iron deprivation toxicity. AB - Recent studies have suggested that iron deprivation may represent a useful new approach in cancer therapy, and several strategies for producing such deprivation are now under investigation. Thus, for example, we recently provided evidence that combined treatment with the iron chelator deferoxamine and an IgG monoclonal antibody against the transferrin receptor (ATRA) produces synergistic inhibition of hematopoietic tumor cell growth in vitro (J. D. Kemp, K. M. Smith, L. J. Kanner, F. Gomez, J. A. Thorson, and P. W. Naumann, Blood, 76: 991-995, 1990). The current study is an attempt to analyze the mechanisms responsible for the synergistic interaction. The data show that a single IgG ATRA can produce up to 75% inhibition of iron uptake while having little effect on DNA synthesis; this suggests that tumor cells either take up or have stored amounts of iron well in excess of that required to support immediate metabolic needs. When deferoxamine and the IgG ATRA are used together, the effects on iron acquisition and receptor down-modulation are either additive or subadditive but are clearly not synergistic. Overall, the findings suggest that the IgG ATRA produces an injury to iron uptake that is just below a critical threshold and that the additional effect provided by the iron chelator is sufficient to exceed that threshold and produce a rapid depletion of iron pools that are vital for short-term DNA synthesis. IgG ATRAS thus seem to be of even greater interest as therapeutic reagents, and further study of their properties and of how they interact with deferoxamine appears to be warranted. PMID- 1638530 TI - Development of a murine lymphoma model system for the characterization of natural killer:tumor cell interactions. AB - We have developed a model system which can be utilized for characterizing both the molecular basis of natural killer (NK):tumor interactions and the consequences of these interactions on tumor growth in vivo. This model system consists of several tumor lines which were derived from the murine lymphoma ASL1w under conditions which permitted the isolation of clonal lines that differ in their susceptibility to NK-mediated lysis. The NK-resistant clones used in this study (AW5J and AW5E) were susceptible to cytotoxic T-lymphocyte-mediated lysis and thus appear to be resistant to lytic processes utilized uniquely by NK cells. In competitive (cold target) inhibition assays, the AW5J clone did not inhibit NK recognition as well as the NK-sensitive clones. Thus AW5J may not be efficiently recognized by NK cells. The AW5E clone, on the other hand, competitively inhibited NK recognition as efficiently as the NK-sensitive clones; therefore, AW5E appears to evade a post-recognition event which is required for NK-mediated lysis. The susceptibility of these clones to killing by NK cells directly correlated with their lethality, suggesting that NK cells regulated the growth of these tumors in vivo. The level of host NK activity was also an important determinant of the level and site of tumor localization. Two-step immunofluorescence assays and flow cytometric analysis were used to quantitate the number of tumor cells in the bone marrow, spleen, and lymph nodes of mice with augmented or depleted NK activity. Increasing host NK activity decreased the number of tumor cells in each organ which could support the growth of the particular tumor tested. Furthermore, the extent of NK regulation was dependent, in part, upon the susceptibility of the particular tumor to NK-mediated lysis and the site of tumor growth. Thus, the data presented here demonstrate the utility of the ASL1w-derived clones as a model system which can be used to delineate the requirements and consequences of NK:tumor interactions. PMID- 1638531 TI - Effect of bivalent interaction upon apparent antibody affinity: experimental confirmation of theory using fluorescence photobleaching and implications for antibody binding assays. AB - The affinity of a monoclonal antibody for its tumor-associated antigen is one of several parameters governing in vivo monoclonal antibody distribution. However, there is a lack of apparent correlation between the affinity of a bivalent monoclonal antibody measured using equilibrium binding experiments and its in vivo delivery. Furthermore, differences in the reported affinity for identical antibody/antigen pairs are quite common in the literature. In this paper, both of these discrepancies are addressed in terms of variation in avidity due to bivalent interaction. The enhancement of avidity afforded by bivalent attachment is addressed theoretically by extending the model of Crothers and Metzger (Immunochemistry, 9: 341-357, 1972). Theoretical assessment of Lineweaver-Burk, Scatchard, Steward-Petty, Langmuir, fluorescence recovery after photobleaching, and Sips models demonstrates quantitatively that the measured affinity using equilibrium binding experiments may vary over four orders of magnitude with similar variation in experimental cellular antigen density. Further, the measured affinity is a function of the experimental protocol. Predictions of avidity enhancement were confirmed experimentally using fluorescence recovery after photobleaching. These experiments measured the equilibrium binding constant and concentration of binding sites for an immunoglobulin G monoclonal antibody and its F(ab) fragment directed against the rabbit VX2 carcinoma cell line. Bivalent binding data agree quantitatively with those predicted by the bivalent model with no adjustable parameters. It is concluded that bivalent equilibrium binding constants are useful only in antibody screening, where experimental conditions are identical for all series. They must be used with caution in predicting in vivo antibody distribution, and it is recommended that the intrinsic, monovalent affinity be measured in tandem with any bivalent antibody study as a standard reference. PMID- 1638532 TI - Gene- and strand-specific damage and repair in Chinese hamster ovary cells treated with 4-nitroquinoline 1-oxide. AB - 4-Nitroquinoline 1-oxide (4NQO) is a model chemical carcinogen that has often been referred to as a UV mimetic agent. Previous studies have indicated that UV induced pyrimidine dimers are repaired preferentially and strand-specifically in actively transcribing genes. In the current study we have examined the gene specific and strand-specific repair of 4NQO in Chinese hamster ovary B-11 cells treated with 2.5 microM 4NQO. The methodology used for detecting adducts involved the treatment of DNA from 4NQO-exposed cells with uvrABC excinuclease, which incises DNA at adduct sites, followed by denaturing gel electrophoresis of DNA, Southern hybridization, and probing for the sequence of interest. We examined the active and inactive coding regions of the DHFR gene, the active adenine phosphoribosyltransferase gene, relatively inactive c-fos oncogene, and the mitochondrial genome for 4NQO adducts. Initial 4NQO adduct levels found in these genes varied from 1.10 to 1.52 adducts/10 kilobases. Little difference in repair was found between active coding and inactive regions of the DHFR gene, or between DHFR, adenine phosphoribosyltransferase, and c-fos genes, which are transcribed at different levels. Approximately 71% of 4NQO adducts were repaired within 24 h in all gene sequences examined. During this same time period, approximately 51% of adducts were repaired from the genome overall, as determined by comparing the removal of bound radiolabeled 4NQO to total DNA. The results indicate that 4NQO adducts, unlike UV light-induced cyclobutane pyrimidine dimers (UV dimers), are not preferentially repaired in transcriptionally active genes. However, there may be regions of the genome that are not repaired with the same efficiency as the specific genes examined here. In addition, little to no difference was observed in the repair of 4NQO adducts in the transcribed and nontranscribed strands of the DHFR gene, a finding which is also in contrast to results with UV dimers. Interestingly, 4NQO adducts, unlike UV dimers, were removed from the mitochondrial genome, suggesting that repair of select lesions occurs in this organelle. Thus, there appear to be some differences in the repair pathways operating for 4NQO adducts and UV dimers, particularly with respect to gene- and strand-specific DNA repair. PMID- 1638533 TI - Targeting of tumor cells and DNA by a chlorambucil-spermidine conjugate. AB - Many tumor cells, including murine ADJ/PC6 plasmacytoma cells, possess an active energy dependent polyamine uptake system which selectively accumulates endogenous polyamines and structurally related compounds. We have attempted to target the cytotoxic drug chlorambucil to a tumor possessing this uptake system by conjugating it to the polyamine spermidine. Furthermore, since polyamines have a high affinity for DNA, the attachment of spermidine to chlorambucil should also facilitate its targeting to DNA. This was supported by the observation that the chlorambucil-spermidine conjugate was approximately 10,000-fold more active than chlorambucil at forming interstrand crosslinks with naked DNA. In vitro cytotoxicity and in vivo antitumor studies were carried out using the ADJ/PC6 plasmacytoma. In vitro, using [3H]thymidine incorporation to assess cell viability following a 1-h exposure to control and polyamine depleted ADJ/PC6 cells, chlorambucil-spermidine was 35- and 225-fold, respectively, more toxic than chlorambucil. The increased toxicity of the conjugate compared to chlorambucil was possibly due to enhanced DNA binding and/or facilitated uptake via the polyamine uptake system. The enhanced toxicity of the conjugate but not chlorambucil by prior polyamine depletion with difluoromethylornithine, together with the observation that the conjugate but not chlorambucil competitively inhibited spermidine uptake into tumor cells, supported the suggestion that the conjugate utilized the polyamine uptake system. In vivo following a single i.p. dose, the conjugate was 4-fold more potent than chlorambucil in its ability to inhibit ADJ/PC6 tumor growth in BALB/c mice. However, the therapeutic index was not increased. Our results support the hypothesis that polyamines linked to cytotoxics facilitate their entry into tumor cells possessing a polyamine uptake system and increase their selectivity to DNA. This may have therapeutic application in the delivery of cytotoxic agents linked to polyamines to certain tumors. PMID- 1638534 TI - Abnormal structure and expression of the p53 gene in human ovarian carcinoma cell lines. AB - In an effort to analyze molecular mechanisms of human ovarian carcinogenesis, we studied the structure and expression of the p53 gene in different cell lines established from human ovarian carcinomas. In all six lines (PA-1, Caov-3 and -4, OVCAR-3, SK-OV-3, and Kuramochi), p53 abnormalities were detected. In the SK-OV-3 cell line, Southern analysis suggested the presence of sequence deletions/rearrangements in at least one allele of the p53 gene, and transcripts were not detectable by either Northern or polymerase chain reaction analysis. Sequence analysis of the entire coding region of the p53 gene revealed point mutations resulting in codon changes of a highly conserved region of the protein in four cell lines, Caov-3 and -4, OVCAR-3, and Kuramochi. In the Caov-3 cell line, the point mutation resulted in chain termination at codon 136. Quantitation of p53 protein by immunoprecipitation analysis revealed a 6-fold higher than control cell level in PA-1. By contrast, p53 protein was not detectable in lines Caov-3 and SK-OV-3. We conclude that altered levels of p53 gene expression and/or mutant forms of the p53 gene product are associated with all human ovarian cancer cells tested. PMID- 1638535 TI - Inhibition of proliferation by c-myb antisense RNA and oligodeoxynucleotides in transformed neuroectodermal cell lines. AB - Transfection of a neuroblastoma cell line with expression vectors containing two different segments of human c-myb complementary DNA in antisense orientation yielded far fewer transfectant clones than did the transfection with the identical segments in sense orientation. In cell clones expressing c-myb antisense RNA, levels of the c-myb protein were down-regulated and the proliferation rate was slower than that of cells transfected with sense constructs or the untransfected parental cell line. Treatment of neuroblastoma and neuroepithelioma cell lines with a c-myb antisense oligodeoxynucleotide strongly inhibited cell growth. These data indicate a definite involvement of c myb in the proliferation of neuroectodermal tumor cells extending the role of this protooncogene beyond the hematopoietic system. The availability of cell clones that transcribe c-myb antisense RNA provides a useful tool to study the involvement of other genes in the proliferation and differentiation of neuroblastoma cells. PMID- 1638537 TI - Expression of platelet-derived growth factor-independent phenotypes in BALB/c 3T3 cell variant with high susceptibility to chemically or physically induced neoplastic cell transformation: dissociation from activation of protein kinase C. AB - A31-I-13, a clonal cell variant of nontransformed BALB/c 3T3 that is highly susceptible to chemically or physically induced malignant cell transformation but is not sensitive to cell killing or susceptible to induced somatic cell mutation compared with another less transformation-susceptible A31-I-1 cell variant, was previously found to be constitutively competent [platelet-derived growth factor (PDGF)-independent] to synthesize DNA (M. Tatsuka et al., J. Cell. Physiol., 139: 18-23, 1989). The present study has demonstrated that density-arrested, quiescent A31-I-13 cells autonomously exhibit disruption of actin filamentous bundles and perturbations of dynamic morphology. PDGF induced these cytoskeletal modulations in quiescent A31-I-1 cells, which require PDGF for the induction of DNA synthesis. Furthermore, the cytoskeletal modulations of quiescent A31-I-13 cells were not accompanied by an increased production of plasminogen activators, activation of protein kinase C, or phosphorylation of a Triton X-100-soluble protein (molecular weight, 90,000) known as 80K, a major substrate for protein kinase C. However, these modulations were accompanied by the tyrosine phosphorylation of Triton X-100-insoluble (cytoskeletal) proteins with molecular weights of 24,000, 32,000-33,000, and 36,000. These Triton X-100-insoluble proteins, as well as the 80K protein, were phosphorylated by the exposure of quiescent A31-I-1 cells to PDGF. Thus the pathway for producing the transformation-susceptible phenotype in A31-I-13 appears to coincide with the PDGF signaling pathway but does not involve the protein kinase C pathway. PMID- 1638536 TI - Pyrimidine dimer removal enhanced by DNA repair liposomes reduces the incidence of UV skin cancer in mice. AB - UV exposure has been linked to skin cancer in humans by epidemiology and the rare genetic disease xeroderma pigmentosum. However, UV produces multiple photoproducts in DNA, and their relative contribution is uncertain. An enzyme which specifically repairs cyclobutane pyrimidine dimers in DNA, T4 endonuclease V, was encapsulated in liposomes for topical delivery into mouse and human skin. In both species, liposomes applied after UV exposure localized in the epidermis and stimulated the removal of cyclobutane pyrimidine dimers. UV-irradiated mice treated with these liposomes had a dose-dependent decrease in the incidence of squamous cell carcinoma compared to controls. The results demonstrate that unrepaired cyclobutane pyrimidine dimers in DNA are a direct cause of cancer in mammalian skin. PMID- 1638538 TI - Effect of testosterone on the growth properties and on epidermal growth factor receptor expression in the teratoma-derived tumorigenic cell line 1246-3A. AB - 1246-3A is an insulin-independent tumorigenic cell line isolated from the C3H mouse teratoma-derived adipogenic cell line 1246. In the present paper, we have demonstrated that testosterone inhibits the in vivo tumorigenic properties of the 1246-3A cells. Castrated male mice receiving injections of 1246-3A cells developed larger tumors at a higher frequency than sham-operated animals. Administration of testosterone to castrated male mice resulted in a dramatic decrease in tumor development. In vitro studies indicated that testosterone inhibited by 50% the proliferation of the 1246-3A cells in culture. However, growth inhibition was observed only if the cells had been cultivated in the presence of testosterone for at least 4 days. In contrast, testosterone had little effect on the proliferation of the parent cell line 1246. Binding of several polypeptide growth factors was examined in cells cultivated in the absence and in the presence of testosterone. Testosterone increased 125I-EGF specific binding to 1246-3A cells. Scatchard analysis of EGF binding indicated that testosterone treatment induced a 2.4-fold increase in the number of cell surface EGF binding sites. This was accompanied by an increase in the intensity of cross-linked EGF receptors on the cells treated with testosterone. In addition, 1246-3A cells cultivated for 9 days in the presence of testosterone displayed a 10-fold increase in the level of EGF receptor mRNA when compared to 1246-3A cells maintained in its absence. Similar to its action on cell proliferation, the increase in EGF receptor number and mRNA expression was observed mainly if 1246-3A cells had been exposed to testosterone for 9 days. The data presented in this paper demonstrate that both in vivo and in vitro, testosterone induces in the teratoma-derived 1246-3A cell line phenotypic changes such as growth inhibition and modulation of EGF receptor expression. PMID- 1638539 TI - Diminished leukocyte-endothelium interaction in tumor microvessels. AB - Leukocyte-endothelium interaction in vivo consists of the rolling of leukocytes along the vascular wall and, under certain conditions, their adherence to endothelial cells. In a rat tumor microcirculation model (mammary adenocarcinoma implanted in rat skinfold window chamber), we demonstrated that this interaction, measured as flux of rolling leukocytes and density of adhering leukocytes, was significantly reduced in tumor microvessels compared to normal microvessels, both under control conditions and during inflammation induced by N formylmethionylleucylphenylalanine (1 microM), bacterial lipopolysaccharide (1 microgram/ml), or tumor necrosis factor alpha (500 units/ml). We also measured the blood flow shear rate in the tumor and normal microvessels and found that the difference in shear rate between the two types of microvessels could not account for the differences in leukocyte-endothelium interaction. The diminished leukocyte-endothelium interaction in tumors under various stimulated conditions suggests that a number of adhesion molecules may not be expressed properly on tumor endothelial cells. PMID- 1638540 TI - The pattern of p53 mutations in Burkitt's lymphoma differs from that of solid tumors. AB - Available evidence suggests that, among hematological malignancies, p53 is most often mutated in Burkitt's lymphoma (BL). However, much of the published data is based on cell lines. We have, therefore, analyzed BL biopsies to determine more accurately the frequency and pattern of p53 mutations in primary tumors and to determine whether there are differences among the various subtypes of BL. Among 27 BL biopsies from South Africa, we have observed mutations in the p53 gene (exons 5 through 8) in 37% of tumors. The higher frequency of mutations in cell lines (70%) suggests that mutation of p53 may be associated with tumor progression. Summarizing available data we conclude that the presence of mutated p53 in BL is independent of the geographic origin of the tumor, the 8;14 chromosomal breakpoint locations and Epstein-Barr virus association. We also find that the mutational spectrum of p53 in BL differs from that observed in nonlymphoid tumors. More than 50% of mutations in BL are clustered in a small stretch of 33 amino acids (codons 213 to 248). Interestingly, codon 213 appears to be as frequently mutated as codon 248. Conversely, codon 273, often mutated in solid tumors, is rarely involved in BL. PMID- 1638541 TI - Murine bladder carcinoma cells present antigen to BCG-specific CD4+ T-cells. AB - Intravesical administration of Bacillus Calmette-Guerin (BCG) is the most effective therapy for superficial transitional cell carcinoma of the bladder although its mechanism of action is not known. To determine if bladder tumors are capable of antigen presentation and thus might interact directly with BCG specific T-cells, we studied the murine bladder tumor MB49. MB49 (MHC Class II negative) (IA-), when induced to express IA with interferon, presented BCG to specific CD4+ T-cells obtained from bladder-draining lymph nodes following intravesical BCG administration. This interaction resulted in antigen- and IA dependent interleukin 2 and tumor necrosis factor production. Interferon also induced MB49 IA expression in vivo. This first demonstration of antigen presentation by epithelial tumors supports new approaches to immunotherapy of these malignancies. PMID- 1638543 TI - Tumor suppressor genes, the cell cycle and cancer. PMID- 1638542 TI - Correspondence re: Giovanna Caderni et al., Effect of dietary carbohydrates on the growth of dysplastic crypt foci in the colon of rats treated with 1,2 dimethylhydrazine. Cancer Res., 51:3721-3725, 1991. PMID- 1638544 TI - Genetic alterations underlying colorectal tumorigenesis. AB - Colorectal tumours have proven to be an excellent system in which to identify and study the genetic alterations involved in the development of a common human neoplasm. A prevalent view is that colorectal tumours appear to arise as the result of multiple genetic alterations in the alleles of both oncogenes and tumour suppressor genes. The accumulation of genetic alterations appears to accompany the clinical and biological progression of the tumours and may determine the phenotype of the tumour cells. In addition to the many somatic alterations identified at various stages of colorectal tumour development, recent studies have led to the identification of the adenomatous polyposis coli (APC) gene, which, when mutated in the germline, predisposes to the development of colorectal tumours. On the basis of studies of inherited and somatic mutations in colorectal tumours, a genetic model for colorectal cancer development has been proposed. Although the model is undoubtedly incomplete, it nevertheless provides a useful framework for further studies of the multiple events that underlie human tumour initiation and progression. Numerous questions remain to be answered, including identification of the normal function of the genes implicated in tumorigenesis, how mutations in these genes arise and are selected for and what the relative contribution of the altered genes is to various stages of the neoplastic process. Nevertheless, an optimistic outlook is that fundamental insights into the pathogenesis of human cancer are within our reach. PMID- 1638545 TI - Friend virus induced murine erythroleukaemia: the p53 locus. AB - The development of Friend virus induced murine erythroleukaemia is associated with specific genetic events. One of these events is loss of wild type p53 expression, which can occur by internal deletion or proviral insertion in the p53 gene and by single point mutations in the coding sequence. In all cases, the corresponding wild type allele is absent. The high frequency of observed p53 mutations strongly suggests that inactivation of p53 may be an obligatory step in the development of Friend disease. Further evidence that abrogation of normal p53 expression contributes to the development of malignant clones was provided by in vitro reconstitution experiments in Friend cell lines: whereas exogenous mutant p53 was stably expressed in p53 negative FCLs, long term wild type p53 expression was not detected. Friend erythroleukaemia arises as a late consequence of infection of susceptible mice with Friend virus. In addition to p53 gene mutations, proviral insertions occur frequently adjacent to one of two cellular genes, Spi-1/PU.1 or Fli-1. Aberrant expression of these genes may therefore be involved in virus induced erythroleukaemia. Interaction of SFFV env gp55 with the EPO-R also appears to be important in providing a mitogenic signal to infected cells. The order in which these events occur and whether the order is relevant to the progression of the disease are not known. Investigation of the stepwise appearance of these events could provide information on the possible interactions of the gene products involved. Abrogation of normal p53 expression is not restricted to Friend erythroleukaemia: the observation of p53 mutations and allele loss in human breast, lung, colon and hepatocellular carcinomas and in leukaemia suggests that mutation of p53 may be the most common genetic abnormality detected in human cancer (reviewed in this issue). Studies of p53 expression in FCLs provided an early indication that p53 was a tumour suppressor gene. Further studies of the mechanisms by which wild type and mutant p53 affect the growth of p53 negative FCLs may reveal important biochemical properties of p53 in relation to cell cycle control and differentiation of erythroid cells. PMID- 1638546 TI - Functional analysis of the retinoblastoma gene product and of RB-SV40 T antigen complexes. PMID- 1638547 TI - The retinoblastoma gene and gene product. AB - Retinoblastoma, an uncommon childhood cancer of the eye, sometimes occurs in families but is often sporadic. Cytological analysis suggested that the retinoblastoma gene resided on chromosome 13 band q14. Subsequent isolation of the RB gene from this locus allowed a more detailed analysis, showing that both copies of RB are mutated or lost in retinoblastoma, a finding that has been extended to a surprising number of other malignancies. In familial retinoblastoma, one copy of RB is mutant in the conceptus, consistent with the familial predisposition to the disease and indicating that a single wild type copy is sufficient for normal development. These studies provided the first good evidence that loss of a gene function correlated with tumorigenesis and led to the concept of "tumour suppressor genes", which have an important negative influence on the regulation of cell growth. Examinations of the biological properties of the gene product are consistent with this proposed role in cell proliferation. Further insight into the potential molecular mechanisms concerned has come from observations showing an association of some viral oncoproteins with the RB gene product. Thus, there is strong evidence that the RB protein has a key role in the integrated network of signals that control the cell cycle. PMID- 1638548 TI - The p53 tumour suppressor gene and product. PMID- 1638549 TI - Transforming growth factor-beta. AB - This chapter has described some of the most salient features of the biology of the TGF-beta s. The TGF-beta s are of great interest as growth inhibitors, regulators of cell phenotype and regulators of cell adhesion. The various TGF beta isoforms are highly conserved and display a complex pattern of interactions with multiple membrane receptor components. Activation of these receptors leads to inhibition of epithelial cell proliferation by a mechanism that may involve proteins related to the growth suppressor, RB. TGF-beta receptors are also coupled to mechanisms that control expression of differentiation commitment genes and differentiated cell functions. TGF-beta can affect cell proliferation and differentiation through indirect mechanisms involving regulation of expression of cytokines, extracellular matrix molecules and their respective receptors. These responses strongly influence the growth and phenotype of an array of cell types. Excess or reduced TGF-beta activity may contribute to the pathogenesis of certain fibrotic disorders and certain hyperproliferative disorders including cancer, respectively. PMID- 1638550 TI - Antitumor effects of interleukin-2 and mismatched double-stranded RNA, individually and in combination, against a human malignant melanoma xenograft. AB - The antitumor effects of recombinant interleukin-2 (rIL-2) and mismatched double stranded RNA (dsRNA) were assessed in tissue culture and in a nude mouse model. Mismatched dsRNA did not show a direct antiproliferative effect against the human malignant melanoma cell line, BRO, in tissue culture. However, treatment of the BRO cells with up to 1000 units/ml rIL-2 in culture showed a slight increase in growth rate. Combined rIL-2/mismatched dsRNA treatment also demonstrated a similar slight enhancement of growth. Nude mice bearing subcutaneous tumors were treated by intraperitoneal injection of low doses (5000-20,000 units) of rIL-2 and mismatched dsRNA (500 micrograms). The in vivo tumor growth was significantly inhibited by the combined treatments (P less than 0.05) and survival was significantly increased (P less than 0.05). Measurement of cytotoxicity using splenocytes from treated animals showed significant augmentation of lytic activity against natural killer (NK)-sensitive YAC-1 cells in all rIL 2/mismatched dsRNA treatment groups, compared to the individual treatments or controls (P less than 0.05). Cytotoxicity of the splenocytes against the NK resistant BRO cells was also augmented in animals treated with mismatched dsRNA and the highest rIL-2 dose utilized here (P less than 0.01). Renal, liver, and hematological toxicity was evaluated by measurement of blood urea nitrogen, creatinine, serum asparrtate aminotransferase, and a complete blood count with differential. There were no significant differences in these parameters in any of the treatment groups. Similarly, no differences in weight of the animals was seen in any treatment group. These results indicate that the combination of low-dose rIL-2 and mismatched dsRNA can potentiate host-mediated antitumor effects, yielding increased survival, without significant toxicity. PMID- 1638551 TI - Cytotoxic functions of blood mononuclear cells in patients with colorectal carcinoma treated with mAb 17-1A and granulocyte/macrophage-colony-stimulating factor. AB - Unconjugated monoclonal antibodies (mAb) may induce tumour regression in patients. The mechanisms of action are complex. Antibody-dependent cellular cytotoxicity (ADCC) is considered one of the effector functions. Augmentation of the killing capacity of cytotoxic cells may thus be a way to increase the therapeutic potential of mAb. Granulocyte/macrophage-colony-stimulating factor (GM-CSF) has been shown to enhance this function in vitro. Eighteen patients with metastatic colorectal carcinoma received GM-CSF (250 micrograms m-2 day-1 s.c.) for 10 days and a single infusion of the anti-(colon carcinoma) mAb 17-1A (mouse IgG2A) (400 mg) on day 3 of the cycle. The cycles were repeated once a month four times. Neutrophils, eosinophils, monocytes and lymphocytes increased significantly in a biphasic way. However, at the fourth cycle the rise in white blood cells was significantly lower compared to the preceding courses. ADCC (SW948, a human CRC cell line,+mAb 17-1A) or peripheral blood mononuclear cells (PBMC) was significantly (P less than 0.05) augmented by day 6 of a cycle and then declined gradually and, at the end of a cycle, the ADCC activity had returned to the pretreatment level. The spontaneous cytotoxicity of PBMC against the natural-killer-resistant cell line, SW948, varied in a similar way. During GM CSF treatment there was also a significant increase in FcRI+ (CD64), FcRII+ (CD32), FcRIII+ (CD16) and CD14+ cells but not of CD56+ cells. PMID- 1638552 TI - Comparative biological properties of a recombinant chimeric anti-carcinoma mAb and a recombinant aglycosylated variant. AB - It has been demonstrated previously that the degree of glycosylation of a molecule may alter its pharmacokinetic properties and, in the case of an antibody, its metabolism and other biological properties. Transfectomas producing aglycosylated chimeric B72.3(gamma 1) pancarcinoma monoclonal antibody (mAb) were developed by introduction of the eukaryotic expression construct pECMgpB72.3 HuG1 agly, into SP2/0 murine myeloma cells producing the chimeric kappa chain of mAb B72.3. After cell cloning, one subclone with the highest binding to the TAG-72 positive human colon carcinoma was designated mAb aGcB72.3, and its biological and biochemical properties were compared with those of the chimeric B72.3(gamma 1), designated mAb cB72.3. Polyacrylamide gel electrophoresis showed that under non-reducing conditions, the molecular masses of the aGcB72.3 and cB72.3 mAbs were 162 kDa and 166 kDa respectively. The heavy chain of mAb aGcB72.3 had a slightly faster mobility than that of cB72.3, while the mobility of the light chains of the two chimeric mAbs was similar. No difference was observed in the isoelectric points of either chimeric mAb. Liquid competition radioimmunoassays demonstrated that the aGcB72.3 and cB72.3 mAbs have comparable binding properties to TAG-72. These studies demonstrate that aglycosylation of the chimeric IgG1 mAb B72.3 at the CH2 domain, as has been shown for other mAbs [Dorai H., Mueller B., Reisfeld R. A., Gillies S. D. (1991) Hybridoma 10:211; Morrison S. L., Oi V. T. (1989) Adv Immunol 44:65], eliminates antibody-dependent cell-mediated cytotoxicity activity, but does not substantially alter affinity or plasma clearance in mice. These studies also demonstrate for the first time (a) no difference in plasma clearance of an aglycosylated and a chimeric mAb in a primate after i.v. inoculation; (b) a difference (P less than or equal to 0.05) in mice in the more rapid peritoneal clearance of a chimeric mAb versus an aglycosylated chimeric mAb; (c) higher (0.05 less than or equal to P less than or equal to 0.1) tumor: liver ratios at 24, 72 and 168 h using 111In-labeled aglycosylated chimeric mAb versus chimeric mAb. Since the liver is the major site of metastatic spread for most carcinomas, slight differences in tumor to normal liver ratios may be important in diagnostic applications. These studies thus indicate that comparative analyses of a novel recombinant construct (i.e., aglycosylated) and its standard chimeric counterpart require documentation in more than one system and are necessary if one is ultimately to define optimal recombinant/chimeric constructs for diagnosis and therapy in humans. PMID- 1638554 TI - An extract of seeds from Aeginetia indica L., a parasitic plant, induces potent antigen-specific antitumor immunity in Meth A-bearing BALB/c mice. AB - The antitumor activity of an extract of seeds from Aeginetia indica L., a parasitic plant, was investigated. BALB/c mice, inoculated i.p. 1 x 10(5) syngeneic Meth A tumor cells, were administered 2.5 mg/kg A. indica extract i.p. every 2 days from day 0. The untreated mice died of an ascitic form of tumor growth within 21 days, whereas all the treated mice completely recovered from tumor challenge without any side-effects. The extract did not exert direct cytotoxic activity against Meth A in vitro. Mice that survived after the first challenge as a result of A. indica treatment overcame the rechallenge with homologous Meth A without additional administration of the extract. On the other hand, those mice could not survive after rechallenge with Meth 1 tumor cells, which were also established in BALB/c mice but were different in antigenicity from Meth A, suggesting the development of antigen-specific concomitant immunity in the A. indica-cured mice. In the induction phase of antitumor resistance in this system, CD4+ T cells appeared to be the main contributors, since in vivo administration of anti-CD4 mAb completely abolished such resistance. In contrast, anti-CD8 mAb administration did not influence the effect of A. indica. The importance of CD4+ T cells in antitumor immunity was again clarified by Winn assay; that is, spleen and lymph node cells depleted of CD4+ T cells in vitro prior to assay abolished antitumor activity on co-grafted Meth A tumor cells in vivo. PMID- 1638553 TI - Glycosidically bound sialic acid levels as a predictive marker of postoperative adjuvant therapy in gastric cancer. AB - A group of 293 gastric cancer patients were examined to see if the preoperative value of glycosidically bound sialic acid is a predictor of prognosis and effectiveness of postoperative adjuvant therapy. All patients had gastrectomies and were histologically confirmed to have primary adenocarcinoma of the stomach. Some patients then received either postoperative adjuvant chemotherapy or immunochemotherapy. Patients with sialic acid levels less than 74.5 mg/dl survived significantly longer than those with sialic acid levels of 74.5 mg/dl or of 85.3 mg/dl and over. No significant differences in survival were found among patients treated by gastrectomy alone, gastrectomy plus chemotherapy and gastrectomy plus immunochemotherapy. However, patients with abnormally elevated levels of sialic acid survived significantly longer when they were treated with immunochemotherapy after gastrectomy than those treated by gastrectomy alone or with chemotherapy after gastrectomy. By using Cox's multivariate regression model, pTNM stages, postoperative adjuvant therapy (chemotherapy and immunochemotherapy) and preoperative serum levels of sialic acid were examined as prognostic variables. Postoperative therapy was a significant prognostic variable in patients with abnormally elevated levels of sialic acid. The preoperative serum level of sialic acid is a promising predictive marker of the response to postoperative adjuvant immunochemotherapy. PMID- 1638555 TI - Immunotargeting of daunomycin to localized and metastatic human colon adenocarcinoma in athymic mice. AB - A monoclonal antibody (designated SF25), which recognizes a protein antigen expressed on a large number of human colon carcinomas, was used for drug targeting. Daunomycin-antibody conjugates were prepared by two previously described procedures. In one, the drug was bound to the antibody through a spacer of small molecular mass (cis-aconitic acid), while in the other a dextran bridge served as the link between drug and antibody. High substitution rates of drug to antibody were obtained using the latter binding procedure. Both conjugates were tested in vitro against two human colon carcinoma cell lines, LS180 and KM-12. The efficacy of a daunomycin-dextran-SF25 antibody conjugate was tested against colon carcinoma LS180 tumors transplanted at different sites into athymic mice. The specific conjugate was significantly more inhibitory to a subcutaneous tumor growth than its components or their mixture. SF25 antibody alone showed antitumoral effects against all three forms of transplanted tumor tested, namely, local, metastatic or intrahepatic, whereas daunomycin, on its own, was effective only against the subcutaneous tumor. Binding of daunomycin to dextran partially improved its inhibitory activity against the metastatic tumor. The conjugate, daunomycin-dextran-SF25 antibody reduced the number of metastatic foci, increased the survival rate and delayed death. Yet against lymph node metastases it was not significantly better than a mixture of both constituents. However, results obtained with an intrahepatic tumor, a model that mimics the natural progression of the disease, resembled those described with the subcutaneous tumor. Daunomycin dextran-SF25 antibody was significantly more effective than all components separately and than a mixture of drug and antibody, provided a highly drug substituted conjugate was used. PMID- 1638556 TI - The polysaccharide K (PSK) potentiates in vitro activation of the cytotoxic function in human blood lymphocytes by autologous tumour cells. AB - We have studied the effect of polysaccharide K (PSK) in the in vitro recognition of ex vivo carcinoma, sarcoma and lymphoma cells by the autologous blood lymphocytes. In 4/25 experiments PSK treatment activated the lymphocytes for auto tumour lysis. Tumour cells alone generated lytic activity both in short- (16 h) and in long-term (6 days) mixed lymphocyte/tumour cell cultures (MLTC), in 2/12 and 3/13 cases respectively. The tumours that activated the lymphocytes expressed high levels of major histocompatibility complex (MHC) class I molecules. In vitro cytokine (interferon gamma and tumour necrosis factor alpha) treatment of the tumour cells elevated the amounts of class I antigens and the treated cells acquired stimulatory potential. When PSK was added to the MLTC, in which untreated tumour cells were used, lytic potential was induced in 9/13 short-term and in 11/12 long-term cultures. It is noteworthy that in the presence of PSK the untreated, negative or low-class-I-expressor tumours also activated the cytotoxic function of the lymphocytes in 4/5 long-term and in 6/7 short-term cultures. Even in the case of those lymphocytes that could be activated by PSK or tumour cells alone, the simultaneous exposure was more efficient. The effect of PSK was dose dependent, being optimal at 1 micrograms/ml and 10 micrograms/ml. The presence of EDTA and/or cytochalasin B in the cytotoxic test performed with the activated effectors abrogated the lysis, indicating the requirement of contacts with the effector cells. PMID- 1638557 TI - A phase I study of neuroblastoma with the anti-ganglioside GD2 antibody 14.G2a. AB - Nine patients with neuroblastoma stage IV were treated with the murine monoclonal antibody 14.G2a, directed against disialoganglioside GD2. The antibody was injected daily for 5-10 days and the total applied dosage ranged between 100 mg/m2 and 400 mg/m2. The peak serum levels of mAb 14.G2a ranged from 28 micrograms/ml to 61 micrograms/ml. Pharmacokinetic data obtained in three patients indicated that the serum elimination of mAb 14.G2a fits a two compartment model, with an alpha-half-time (t1/2 alpha) between 0.66 h and 1.98 h and a beta-half-time (t1/2 beta) between 30.13 h and 53.33 h. All patients presented with a human anti-(mouse IgG) antibody response either during or shortly after therapy. Eight patients showed a continuous decrease in complement component C4 during therapy, as well as an initial decrease in C3c and an initial increase in C3a, all suggesting an activation of the complement cascade. Side effects consisted of allergic reactions like pruritus, exanthema, urticaria and of severe pain, predominantly located in the abdomen and lower extremities, which required the use of continuous intravenous morphine. Four patients additionally developed a transient hypertension and one patient experienced a transient nephrotic syndrome. Three patients were treated in an adjuvant setting and are not evaluable for tumor response. Of the remaining six patients, two had a complete remission, two showed a partial remission, and two patients did not respond to treatment. PMID- 1638558 TI - Comment on the interpretation of lymphocyte phenotyping. PMID- 1638559 TI - A modified model of global ischaemia: application to the study of syncytial mechanisms of arrhythmogenesis. AB - OBJECTIVE: The aim was to develop a simple modified global ischaemia preparation to study the relation between ischaemic zone size and the incidence of ischaemia induced and reperfusion induced arrhythmias, to test the hypothesis that arrhythmias are initiated by flow of injury current between the ischaemic zone and the uninvolved myocardium. The new model was used to examine whether injury current suppression is involved in the mechanism of action of a new antiarrhythmic intervention, substitution of chloride anion by nitrate. METHODS: Isolated perfused (Langendorff mode) rat hearts (n = 12 per group) were subjected to 30 min global or regional ischaemia. Ventricular arrhythmia incidence during ischaemia and during reperfusion were related to the size of the involved region. The modified model of global ischaemia employed right intra-atrial superfusion to maintain normal sinus rate and 1:1 atrioventricular (AV) conduction. RESULTS: Sham ligation, low left coronary ligation, high left coronary ligation, and global ischaemia produced, as a percentage of total ventricular weight, 0%, 21.0(SEM 0.8)%, 47.0(1.0)%, and 100% regions of ischaemia (occluded zones). Heart rates were similar in each group and AV block did not occur. The incidences of ischaemia induced ventricular fibrillation (VF) were 0, 17, 75, and 17% with increasing occluded zone sizes. Incidences of reperfusion induced VF were 0, 8, 92, and 92% respectively. The antiarrhythmic action of substitution of extracellular chloride by nitrate, previously shown using models of regional ischaemia, was confirmed in the modified global ischaemia model. CONCLUSIONS: These findings strongly support the theory that current of injury between ischaemia and adjacent non-ischaemic zones is necessary for initiation of ischaemia induced VF, since susceptibility was maximal when ischaemic and uninvolved regions were equivalent in size (and the scope for injury current was maximal) whereas susceptibility was negligible when scope was minimal. In contrast, reperfusion induced VF appears to depend only on the presence and amount of reperfused tissue, indicating that flow of injury current between involved and uninvolved tissue is unnecessary for its initiation. Discrimination of the mechanism of action of antiarrhythmic interventions may be possible since drugs effective solely via amelioration of flow of injury current (or incrementation of collateral flow) will not influence arrhythmias in this model. Modification of injury current and collateral flow do not appear to contribute to the antiarrhythmic action of substitution of extracellular chloride by nitrate. PMID- 1638560 TI - Rate of reflow and reperfusion induced arrhythmias: studies with dual coronary perfusion. AB - OBJECTIVE: The aim was to determine the relationship between the rate of reflow and vulnerability to reperfusion induced arrhythmias. METHODS: Isolated rat hearts, in which left and right coronary arteries were perfused independently, were subjected to transient (10 min) cessation of flow to the left coronary bed. During the subsequent 10 min of reperfusion, flow in the left coronary bed was regulated to create five different reflow profiles (n = 12 per group): (1) immediate restoration of 100% flow which was maintained throughout reperfusion (control); (2) stepwise restoration of flow with 10% flow from 0-1 min, 20% flow from 1-2 min, 40% flow from 2-3 min, 60% flow from 3-4 min, 80% flow from 4-5 min, and 100% flow from 5-10 min; (3) 10% flow from 0-5 min and 100% flow from 5 10 min; (4) 20% flow from 0-5 min and 100% flow from 5-10 min; and (5) 40% flow from 0-5 min and 100% flow from 5-10 min. RESULTS: There were no significant differences between the groups in the incidences of reperfusion induced ventricular tachycardia or fibrillation, which were 100% and 58-92%, respectively. However, the time to onset of reperfusion induced ventricular fibrillation was delayed (p less than 0.05) from 15 (SEM 1) s in group (1) to 191(39), 210(38), and 77(29) s in groups 2, 3, and 4, respectively. No significant delay was observed in group 5. There were no significant differences between the groups in size of ischaemic zone or heart rate. CONCLUSIONS: In crystalloid perfused hearts, restricted reflow delays the time to onset of reperfusion induced ventricular fibrillation but does not reduce the incidence of reperfusion induced ventricular tachycardia or fibrillation. PMID- 1638561 TI - Cardiac autonomic dysfunction and neuroganglionitis in a rat model of chronic Chagas' disease. AB - OBJECTIVE: The aim was to evaluate whether the cardiac parasympathetic function in a rat model of chronic Chagas' disease is impaired as in the human disease, and to correlate the functional state to histopathology of the intrinsic autonomic innervation of heart. METHODS: 70 male Wistar rats 8 months infected with strains Y (n = 22), Sao Felipe (n = 18), and Colombia (n = 30) of Trypanosoma cruzi, were compared with 20 age and sex matched non-infected controls. Baroreflex bradycardia was quantified after multiple bolus injections of phenylephrine (3 to 12 micrograms). For each rat studied a mean was obtained of the absolute and relative (delta %) ratio (index) between the maximum heart rate decrease and the maximum systolic blood pressure increase. RESULTS: For the relative index the means were smaller (p less than 0.05) in the Y [-0.52(SD 0.19)%], Sao Felipe [-0.45(0.28)%], and Colombia [-0.53(0.21%)] subgroups, as well as in the pooled chagasic group [-0.51(0.22)%], than in the control group [ 0.64(0.13)%]. In 32% (7/22), 33% (6/18), and 20% (6/30) of rats infected with Y, Sao Felipe, and Colombia strains, respectively, and in 27% (19/70) of the pooled group rats, the index exceeded the control group mean by -2 SD. After atropinisation, a similar pronounced reduction (p less than 0.01) in the index was observed in all groups [-84(28)% to -95(17)%]; however, rats with depressed bradycardia showed a smaller (p less than 0.05) reduction in the relative index than control rats, at -70(34) v -92(16%). Inflammatory and degenerative lesions of the intrinsic cardiac innervation were observed in 87% of the rats with autonomic dysfunction. Rats with the lesions showed a mean relative index that was smaller than those without lesions, at -0.44(0.23) v -0.64(0.20)% (p less than 0.01), and also smaller than in the controls. CONCLUSIONS: Cardiac autonomic dysfunction expressed by reduced baroreflex bradycardia was detected in rats chronically infected with T cruzi, as in human Chagas' disease. The disturbance, shown for the first time in an animal model of chagasic infection, resulted primarily from impaired efferent parasympathetic activity caused by intrinsic neuroganglionar lesions. PMID- 1638562 TI - Regional myocardial deoxyglucose uptake following electrical stimulation of canine efferent sympathetic cardiopulmonary nerves. AB - OBJECTIVE: The aim was to study the effect of stimulating individual acutely decentralised cardiopulmonary nerves on myocardial uptake of deoxyglucose. METHODS: In 17 open chest anaesthetised dogs the efferent axons of individual decentralised cardiopulmonary nerves were stimulated intermittently throughout 1 h while haemodynamic variables were measured. Tritiated 2-deoxyglucose was injected intravenously at the beginning of stimulation. Atropine was given when a cardiopulmonary nerve with efferent parasympathetic axons was studied. Distribution of label was detected using a multiwire proportional chamber. It was compared to blood concentration of deoxyglucose to permit quantitative mapping of regional myocardial uptake during the stimulation of each nerve. RESULTS: Neural stimulation of most of sympathetic efferent cardiopulmonary nerves increased deoxyglucose uptake in all myocardial tissue. Uptake was greatest in the left ventricle, less in the right ventricle, and least in the left and right atria. Regional myocardial uptake was also observed following individual cardiopulmonary nerve stimulation. Some nerves caused greater uptake than others. Cardiopulmonary nerves which are known to enhance inotropism when stimulated induced little increase of deoxyglucose uptake, whereas other nerves known to exert little positive inotropic effect induced considerable uptake. There was no correlation between haemodynamic changes and deoxyglucose uptake. CONCLUSIONS: It appears that (1) efferent sympathetic axons in one cardiopulmonary nerve can preferentially increase deoxyglucose uptake in specific regions of the myocardium and (2) the mechanisms responsible for enhancement of glucose uptake may differ from those responsible for inotropic responses. PMID- 1638563 TI - Postischaemic hypercontraction is enhanced in ischaemically injured canine myocardium. AB - OBJECTIVE: The aim was to identify the role of calcium flux in the pathogenesis of transient overshoot of regional myocardial contraction after brief ischaemia, ie, postischaemic hypercontraction. METHODS: Ten anaesthetised mongrel dogs were examined under open chest conditions. The left anterior descending coronary artery was initially occluded for 2 min and reperfused for 10 min. A further period of coronary occlusion of 15 min duration was followed by 15 min reperfusion to produce postischaemic regional dysfunction. A third occlusion of 2 min duration was followed by 10 min reperfusion to induce postischaemic hypercontraction. Coronary blood flow was measured using an ultrasonic transit time flow meter. Segment length was measured by ultrasonic microcrystals. RESULTS: Postischaemic hypercontraction after 2 min coronary occlusion was exaggerated in ischaemically injured myocardium. The 10 dogs were divided into two groups, a control group (n = 5) and a verapamil treated group (n = 5), and were exposed to a final 2 min period of coronary occlusion with or without verapamil in the ischaemically injured myocardium. Postischaemic hypercontraction was attenuated in the verapamil treated group compared with the control group. CONCLUSIONS: Exaggeration of postischaemic hypercontraction in ischaemically injured myocardium may be mediated by a trans-sarcolemmal calcium flux. Changes in calcium flux may play a role in the pathogenesis of this phenomenon in the normal myocardium. PMID- 1638564 TI - Whole body heat stress fails to limit infarct size in the reperfused rabbit heart. AB - OBJECTIVE: It has recently been shown that induction of heat stress proteins by whole body heat stress confers myocardial protection in the isolated in vitro rat and rabbit heart. This study extends the above studies by examining the effects of stress protein synthesis on the limitation of infarct size in the in vivo rabbit heart model. METHODS: 30 male New Zealand white rabbits were used. Six rabbits were used for measurement of heat stress protein; 10 were used for infarct size determination in a heat stress group (HS); 14 were used for infarct size determination in a control group. There were 10 exclusions. Under anaesthesia, body temperature was raised to 42 degrees C for 15 min in the HS group. Following 24 hours of recovery rabbits were reanaesthetised and the hearts subjected to a 45 min period of regional ischaemia followed by 3 h reperfusion. The risk zone was defined with fluorescent particles and the infarct area determined by tetrazolium staining. Western blotting showed an increase in the 72 KD heat stress protein in hearts in the HS group. RESULTS: Infarct size as a percent of risk area was 61.4 (SEM 6.4)% (n = 14) in control hearts and 71.8(7.3)% (n = 10) in the HS hearts. These results were not statistically significant. CONCLUSIONS: No protective effect of heat stress could be seen when infarct size was used as the end point. Either the protection seen in earlier studies using the Krebs perfused isolated heart model does not accurately reflect protection against myocardial infarction, or heat stress itself may induce injurious factors in the blood which will negate any direct protective effect to the myocardium in this model. PMID- 1638565 TI - Endothelium bound extracellular superoxide dismutase type C reduces damage in reperfused ischaemic rat hearts. AB - OBJECTIVE: The aim was to determine if endothelium associated extracellular superoxide dismutase type C (EC-SOD C) exerts any protective effect against cardiac damage induced by ischaemia and reperfusion. METHODS: Langendorff perfused rat hearts were subjected to 15 min global ischaemia followed by reperfusion. Prior to the ischaemia the hearts were perfused for 15 min with a buffer containing recombinant human EC-SOD C (rh-EC-SOD C, 20 mg.litre-1), or the corresponding vehicle, followed by extensive perfusion with SOD free medium. RESULTS: In hearts receiving the vehicle, reperfusion was associated with a marked release of creatine kinase into the effluent [28 (SEM 1.5) IU.15 min-1, n = 5] and coronary flow measured 15 min after initiation of reperfusion was reduced by 68% compared to preischaemic flow. In hearts pretreated with EC-SOD C but washed with enzyme free buffer before being subjected to ischaemia, the creatine kinase release was significantly smaller, at 14(2.1) IU.min-1, n = 5 (p less than 0.001), and the reduction in coronary flow less extensive (54%, p less than 0.05, v vehicle). To demonstrate the binding of EC-SOD C to the endothelium, heparin, which releases EC-SOD C from the endothelial surfaces, was added to the perfusate 30 min after initiation of reperfusion. The same amount of EC-SOD C was released to the effluent from previously ischaemic hearts [(12.4(2) micrograms)] as from hearts not subjected to ischaemia [(13.8(1.4) micrograms)]. CONCLUSIONS: Recombinant human EC-SOD type C bound to the endothelial surface reduces the cardiac damage associated with ischaemia and reperfusion. The protective effect was evident both in terms of a reduction of biochemical markers of injury and a better preservation of postischaemic coronary flow. Furthermore, ischaemia and subsequent reperfusion did not cause any alteration in the binding capacity of EC SOD C to the cardiac vasculature. PMID- 1638566 TI - The thromboxane A2 mimetic U46619 worsens canine myocardial hypoperfusion during exercise in the presence of a coronary artery stenosis. AB - OBJECTIVE: The aim was to test the hypothesis that thromboxane A2 can cause vasoconstriction of coronary resistance vessels during exercise in hypoperfused regions of myocardium distal to an arterial stenosis. METHODS: Eight adult mongrel dogs were studied. Chronically instrumented animals with a left circumflex coronary artery Doppler flow meter, hydraulic occluder, and indwelling catheter underwent treadmill exercise at heart rates of 190-200 beats.min-1. Myocardial blood flow was measured with microspheres during unimpeded arterial inflow and in the presence of a coronary stenosis which decreased distal pressure to 42-45 mm Hg. Measurements were repeated during infusion of the thromboxane A2 analogue, U46619. RESULTS: When the occluder was partially inflated to produce a stenosis, blood flow in the region perfused by the stenotic artery was 58 (SEM 6)% of flow in the normally perfused region (p less than 0.01). U46619 (0.01 microgram.kg-1.min-1) caused a further 21 (7)% decrease in blood flow in the region perfused by the stenotic artery (p less than 0.05). The vasoconstriction produced by U46619 was uniform across the left ventricular wall from epicardium to endocardium. U46619 did not significantly decrease myocardial blood flow in the absence of a coronary stenosis. CONCLUSIONS: Even during hypoperfusion produced by a flow limiting arterial stenosis, the coronary resistance vessels remain responsive to the vasoconstrictor effect of thromboxane A2. Liberation of thromboxane A2 during platelet activation at the site of a proximal coronary stenosis may worsen myocardial hypoperfusion by causing vasoconstriction of the distal resistance vessels. PMID- 1638567 TI - Importance of nitric oxide in canine femoral circulation: comparison of two NO inhibitors. AB - OBJECTIVE: The aim was to assess the importance of endothelium derived nitric oxide (NO) in the regulation of vascular tone in the limbs. Changes in the canine femoral circulation were investigated after inhibition of NO synthesis. METHODS: The effects of two NO inhibitors, NG-monomethyl-L-arginine (LNMMA) and NG-nitro-L arginine (NOARG), were compared on basal femoral blood flow and on endothelium dependent (acetylcholine) and endothelium independent (glyceryl trinitrate) vasodilatation in 15 pentobarbitone anaesthetised mongrel dogs. An electromagnetic flow probe was placed on the femoral artery to measure femoral blood flow. One catheter was advanced into the femoral artery proximal to the flow probe for blood pressure recording and another catheter distal to the flow probe for drug infusions. RESULTS: LNMMA (0.28 mumol.ml-1) reduced basal femoral blood flow by 44(SEM 3)%, NOARG (0.07 mumol.ml-1) by 21(4)%, and NOARG (0.56 mumol.ml-1) by 29(3)%. The flow responses to acetylcholine were reduced after LNMMA by 27(8)%, unaltered after NOARG (0.07 mumol.ml-1), and reduced after NOARG (0.56 mumol.ml-1) by 60(7)%. The flow response to glyceryl trinitrate was unaltered. L-arginine re-established femoral blood flow after infusion of LNMMA and NOARG (0.07 mumol.ml-1), but L-arginine did not re-establish femoral blood flow after NOARG (0.56 mumol.ml-1), even when infused in a 60-fold molar excess. CONCLUSIONS: There is a continuous basal release of NO in the canine femoral circulation. The results obtained by infusing LNMMA suggest that more than 40% of basal femoral blood flow is mediated by endothelium derived NO. Whereas LNMMA was more potent than NOARG in reducing basal NO release, NOARG (0.56 mumol.ml-1) reduced acetylcholine induced vasodilatation by as much as 60%. PMID- 1638568 TI - Evaluation of indices of left ventricular contractility and relaxation in evolving canine experimental heart failure. AB - OBJECTIVE: The aim was to evaluate changes in indices of left ventricular contractility and relaxation in relation to changes in loading conditions in dogs with rapid pacing induced heart failure. METHODS: 14 conscious male mongrel dogs were paced at 250 beats.min-1 to severe heart failure, which occurred at 4.2(SD1.9) weeks. Six sham operated dogs served as controls. Right sided pressures were obtained by a thermodilution catheter. Left ventricular pressure and its derived variables were obtained by a high fidelity manometer tipped catheter. Rate corrected velocity of circumferential fibre shortening--end systolic wall stress relations were obtained by simultaneous haemodynamic and echocardiographic studies. RESULTS: In the paced dogs, baseline right atrial pressure, 6.4(2.0) mm Hg, and pulmonary capillary wedge pressure, 7.1(2.5) mm Hg, increased to 13.3(3.1) mm Hg and 34.5(7.1) mm Hg respectively at severe heart failure (both p less than 0.0001). The peak first derivative of left ventricular pressure dP/dt decreased from 1515(274) mm Hg.s-1 at baseline to 975(321) mm Hg.s 1 at severe heart failure (p less than 0.05) while baseline left ventricular end diastolic pressure, 4.4(3.7) mm Hg, and relaxation time constant tau, 18.0(4.5) ms, increased to 37.2(6.6) mm Hg (p less than 0.01) and 51.9(21.4) ms (p less than 0.05) respectively. The shortening-wall stress relation was markedly displaced downward from baseline. Furthermore, weekly studies revealed a major downward displacement of this relation by one week of pacing with no significant further shift at severe heart failure, whereas both end diastolic diameter (preload) and end systolic wall stress (afterload) increased significantly further from one week. In the sham operated dogs, there was no change over time in any of these study variables. CONCLUSIONS: In pacing induced heart failure, there is impairment of left ventricular contractility and relaxation. The major downward shift of the shortening-wall stress relation at one week suggests that left ventricular contractility is impaired early and may be the initiating mechanism of heart failure in this model. PMID- 1638569 TI - Acid optimum kininogenases in canine myocardium and aorta. AB - OBJECTIVE: Canine coronary artery was recently reported to contain a cathepsin like acid optimum enzyme and a kallikrein like alkaline optimum enzyme which cleaved from a crude kininogen preparation a vasodilator uterus contracting substance. The aim of this study was to seek the presence of similar acid optimum enzymes in canine ventricular myocardium and in a large systemic artery, the aorta. METHODS: Aqueous canine tissue extracts were tested for the ability at different pHs to release uterus contracting substance (using rat isolated oestrous uterus) from a kininogen preparation. After gel filtration, the extracts were tested for the presence of arginine-amidase activity (substrate: D Val.Leu.Arg.pNA) and enzymic activity forming bradykinin like immunoreactivity. Tissues were obtained from anaesthetised greyhounds which had been used in control studies and had received no other drug treatment. RESULTS: Ventricular extracts released uterus contracting substance optimally at pH 5.2-5.4, but not at alkaline pH, neither was bradykinin like immunoreactivity formed at alkaline pH. Inhibitor studies and gel filtration showed this activity to be due to a cathepsin-D-like enzyme, molecular weight (MW) 42.6 (SD 0.9) kd, which was an arginine amidase and released bradykinin like immunoreactivity from a plasma kininogen. Aortic extracts showed two pH related peaks of uterus contracting substance formation, at pH 5.2 and (unlike myocardium) at pH 8. Also unlike myocardium, aortic extracts gave two acid optimum kininogenase peaks on gel filtration, with MW 42(4.6) kd and 252(39) kd, respectively. Both peaks released bradykinin like immunoreactivity. CONCLUSIONS: Canine aorta contained an alkaline optimum and two acid optimum enzymes, while ventricle contained only a cathepsin D-like acid optimum enzyme, all of which could form bradykinin like immunoreactivity. The ability of the ventricular enzyme to form a kinin in the slightly acid conditions of myocardial ischaemia may have a protective role. PMID- 1638570 TI - Acute effects of doxorubicin on skinned cardiac muscle fibres of guinea pigs. AB - OBJECTIVE: The aim was to examine the effect of doxorubicin on spontaneous cyclic Ca2+ release from the sarcoplasmic reticulum of skinned fibres, as measured by isometric tension development in EGTA free, Ca2+ free solution. METHODS: Experiments were done on fragments of papillary muscles from the right ventricles of guinea pigs. Skinned fibres were prepared by treatment with saponin. The effects of doxorubicin in concentrations of 2 x 10(-9) to 2 x 10(-5) M on cyclic contractions were evaluated in 20 muscles. The effects of doxorubicin in concentrations of 2 x 10(-7) and 2 x 10(-5) M on pCa-tension relation were examined in 14 muscles treated with Brij-58. RESULTS: Doxorubicin (2 x 10(-9) to 2 x 10(-5) M) increased the frequency of cyclic contractions and induced an incomplete muscle relaxation in a dose dependent manner. Doxorubicin 2 x 10(-7) M had no effect on pCa-tension relation. Doxorubicin 2 x 10(-5) M shifted the pCa tension curve slightly to the left. CONCLUSIONS: An incomplete muscle relaxation is considered to be due to an increase in Ca2+ release from the sarcoplasmic reticulum and a slight increase in the sensitivity of the contractile proteins to Ca2+. These observations suggest that one cause of the intracellular Ca2+ overload induced by doxorubicin, a putative mechanism of the doxorubicin induced cardiomyopathy, is attributable to the direct effects of doxorubicin on the sarcoplasmic reticulum, impairing its ability to sequester Ca2+. PMID- 1638571 TI - Action potential duration and endocardial modulation of myocardial contraction in the ferret. AB - OBJECTIVE: Endocardial endothelium releases substances which modulate myocardial contraction. Selective endocardial removal abbreviates contraction by removing a contraction prolonging substance "endocardin". The aim of the study was to investigate whether changes in action potential duration underlie these contractile effects. METHODS: The contractile effects of shortening the action potential were first characterised, using a potassium channel "opener" cromakalim (3 microM). Transmembrane action potentials were then recorded in isolated ferret papillary muscles before and after endocardial removal. RESULTS: Cromakalim induced action potential abbreviation reduced contractile twitch duration. Endocardial removal itself however did not alter action potential duration. CONCLUSIONS: Endocardial modulation of cardiac contraction does not involve changes in action potential duration. PMID- 1638572 TI - Effect of hypertonicity on contractility of isolated working rat left ventricle. AB - OBJECTIVE: The aim was to evaluate the effect of hypertonic perfusate on isolated left ventricular mechanical and energetic characteristics. METHODS: An isolated working rat heart model was perfused with a hyponatraemic Krebs-Heinseleit bicarbonate buffer (240 mOsmol.litre-1). To this buffer was added increasing amounts of mannitol to achieve 280, 320, and 360 mOsmol.litre-1 perfusates. RESULTS: Left ventricular peak pressure, maximum time derivative of left ventricular pressure (dP/dtmax), and end systolic pressure were all increased to a maximum value at 280 or 320 mOsmol.litre-1 perfusate tonicity. A similar response was evident with cardiac output, which changed from 33.7(SEM 0.6) to 43.5(0.8) ml.min-1 following changing the perfusate tonicity from 240 to 280 mOsmol.litre-1 (p less than or equal to 0.003). However, increasing perfusate tonicity further decreased cardiac output to 36.5(1.3) ml.min-1 at 360 mOsmol.litre-1. Maximal left ventricular elastance remained unchanged during perfusion with increasing perfusate tonicities. CONCLUSIONS: Changing perfusate osmolality using mannitol has a positive inotropic effect at low osmolalities and a negative inotropic effect at perfusate osmolality greater than 320 mOsm.litre 1. PMID- 1638573 TI - Pacemaker current, membrane resistance, and K+ in sheep cardiac Purkinje fibres. AB - OBJECTIVE: The pacemaker current in cardiac Purkinje fibres has been attributed to either a decrease in potassium conductance or an increase in a non-specific (Na-K) conductance. The former mechanism would be associated with an increase in membrane resistance (Rm) and the latter with a decrease in Rm. The aim of this study was to obtain evidence in support of one or other mechanism by measuring Rm during the pacemaker current (Idd) under conditions where there is a small or no extracellular potassium depletion. METHODS: Hearts were obtained from anaesthetised sheep and thin strands of ventricular Purkinje fibres were shortened to less than or equal to 1.6 mm. Purkinje fibres were voltage clamped to potentials positive and negative to the potassium equilibrium potential (EK) using a two microelectrode technique. Small current pulses were superimposed on Idd to measure Rm changes. Procedures were used that decrease either the background potassium current IKl or Idd in order to dissect changes in Rm due to K depletion from those due to Idd. RESULTS: Rm increased during Idd, whether the pacemaker current increased or decreased as a function of time. Increasing [K]o from 2.7 to 5.4 mmol.litre-1 decreased Rm and during hyperpolarising steps increased the instantaneous current but did not change Idd amplitude. In 2.7 mmol.litre-1 K, caesium (Cs, 2 mmol.litre-1) increased the holding current (Ih), had little effect on the instantaneous current, and eliminated Idd and associated Rm changes. In 5.4 and 10.8 mmol.litre-1 K, Cs increased Ih and decreased Idd amplitude and in 10.8 mmol.litre-1 K Cs decreased the instantaneous current on hyperpolarisation. If the current was reversed, Cs decreased but did not abolish it. In normal [K]o, barium (Ba, 0.05-0.5 mmol.litre-1) increased Ih and Rm, reduced the instantaneous current but did not increase Idd amplitude. In high [K]o, Ba instead increased the amplitude and rate of development of Idd. When Cs was applied in the presence of Ba, Idd was reduced or eliminated depending on [K]o. CONCLUSIONS: The changes in membrane resistance during the pacemaker current cannot be accounted for by K depletion and suggest that in the range of diastolic depolarisation the pacemaker current results predominantly from a time dependent decrease in K conductance. PMID- 1638574 TI - Consequences of opiate agonist and antagonist in myocardial ischaemia suggest a role of endogenous opioid peptides in ischaemic heart disease. AB - OBJECTIVE: The aim was to evaluate the effects of an opiate agonist (U50,488H) and an opiate antagonist (naloxone) in myocardial ischaemia. METHODS: A left thoracotomy was performed and the left coronary artery was ligated in adult Sprague-Dawley rats of either sex (350-400 g). Blood pressure, heart rate and electrocardiogram were measured before and after injections of U50,488H or naloxone and throughout the 30 min postligation period. RESULTS: Following coronary artery occlusion, all rats in the control group developed arrhythmias, bradycardia, and hypotension. U50,488H potentiated and naloxone attenuated the ischaemia induced arrhythmias, bradycardia, and hypotension. CONCLUSIONS: The potentiating and blocking effects of U50,488H and naloxone, respectively, suggest that endogenous opioid peptides are involved in the pathophysiology of myocardial ischaemia and play an important role in ischaemic heart disease. PMID- 1638575 TI - Mitochondrial dysfunction observed in situ in cardiomyocytes of rats in experimental diabetes. AB - OBJECTIVE: The aim was to investigate effects of experimental diabetes and insulin treatment on heart myocytes, particularly on the mitochondrial function studied in situ in isolated cardiomyocytes. METHODS: 20 male Sprague-Dawley rats (140-160 g) were made diabetic by intraperitoneal streptozotocin, 70 mg.kg-1. Ten then received daily subcutaneous injections of ultra lente insulin (starting dose of 3 units.d-1) for 7-15 d from the 20th day after streptozotocin. There was a control group of 11 rats. The rats were killed 21-35 d after the induction of diabetes, and heart myocytes were isolated by collagenase digestion. The 45[Ca]2+ uptake of mitochondria in situ in permeabilised myocytes, the transmembrane potential gradient of mitochondria, and the respiration of myocytes, as well as the cell yield and cell [45Ca]2+ uptake, were examined. RESULTS: Mitochondrial uptake of [45Ca]2+ was significantly decreased in the diabetic group compared to control at cytosolic calcium concentrations between 760 nM and 44.6 microM. The mitochondrial potential of diabetic myocytes, estimated from the distribution of [3H]triphenylmethylphosphonium+, was slightly but significantly decreased from the control value. Cell respiration, measured polarographically in the presence of pyruvate and malate or succinate as oxidisable substrates, and with or without 2,4-dinitrophenol, was decreased by diabetes. The rapidly exchangeable [45Ca]2+ content in the myocyte with intact sarcolemmal membrane ("cell Ca2+ uptake") and the yield of cells from heart tissue were also diminished in diabetic rats. These changes were returned to normal by insulin treatment of 7 d or longer. CONCLUSIONS: Insulin deficiency at early stages causes defects of mitochondrial function detectable in situ in cardiomyocytes. This suggests the possibility that such alterations are causative factors in the development of diabetic cardiomyopathy. PMID- 1638576 TI - Effects of progressive myocardial ischaemia on systolic function, diastolic dysfunction, and load dependent relaxation. AB - OBJECTIVE: The aims were to determine (1) the relationship between changes in contractile function (systolic shortening) and the appearance of diastolic dysfunction (postsystolic shortening) during progressive regional left ventricular ischaemia; (2) the effects of increased afterload (acute constriction of the descending thoracic aorta) on ischaemic contractile dysfunction; and (3) the effects of loading during ischaemia on load dependent relaxation. METHODS: Regional myocardial function, using sonomicrometry, was measured in the short and long axes of the apex of the left ventricle of eight open chest anaesthetised dogs (16-20 kg). Progressive apical ischaemia was induced by graded reductions in left anterior descending coronary artery flow (critical constriction, ischaemia 1, ischaemia 2, total coronary occlusion, and postocclusive maximum reactive hyperaemia). Acute afterloading was induced by a snare placed around the descending aorta. RESULTS: Consistent decreases in systolic shortening and increases in postsystolic shortening relative to the total segmental shortening in the short axis of the apical region were seen with worsening ischaemia. Aortic constriction increased the magnitude of apical postsystolic shortening and decreased apical systolic shortening in the short axis during critical constriction, ischaemia 1, and ischaemia 2. Long axis function changed in a qualitatively similar but quantitatively different manner. There was a significant decrease in the load dependency of relaxation with total coronary occlusion. CONCLUSIONS: (1) Changes in systolic and diastolic function occurred concomitantly as mild regional myocardial ischaemia developed and intensified; (2) afterloading significantly worsened regional systolic and diastolic dysfunction during mild ischaemia; and (3) progression of regional ischaemia resulted in loss of load dependent relaxation. PMID- 1638577 TI - Fluoroquinolone antibiotics: properties of the class and individual agents. AB - The broad spectrum of activity and bactericidal nature of the fluoroquinolones, together with their excellent absorption, rapid distribution, and high tissue concentration, make them excellent therapeutic agents for the management of a number of complicated community-acquired and nosocomial infections of the urinary tract, bone and soft tissue, gastrointestinal tract, and prostate, as well as some respiratory tract infections and sexually transmitted diseases. Data are presented and reviewed concerning the in vitro activity, pharmacology, and clinical use of ciprofloxacin, norfloxacin, and ofloxacin, which have been available for some time, and lomefloxacin and temafloxacin, which are recently approved agents. The comparable qualities and differences in activity and clinical applications of these agents are considered. For many infections in selected patients, quinolones are excellent substitutes for parenteral agents. In general, adverse effects have been infrequent and rarely require drug discontinuation. Significant interactions, such as with theophylline and caffeine, have occurred but are quinolone dependent. Antacids can markedly impair the absorption of all quinolones. Because emerging resistance to Pseudomonas and Staphylococcus species have been observed, the improper use of the quinolones must be avoided, and the clinician must be aware that an unfavorable response may signal resistance. The development of future agents with better gram-positive activity, improved gram-negative coverage, and activity against unusual pathogens such as Chlamydia species and Mycobacterium species, will make these oral agents invaluable. Assessing the usefulness and safety of these antibiotics in children is an ongoing challenge. PMID- 1638579 TI - Effects of dilevalol in hypertension assessed by digital pulse plethysmography. AB - For two weeks, with the exception of one case involving long-term therapy, 15 hypertensive patients received 100 mg of dilevalol once daily and seven patients received 50 mg. Blood pressure and heart rate were measured and digital pulse plethysmography (DPG) was performed before and after the two-week trial. Systolic and diastolic blood pressure decreased significantly during treatment; heart rate did not change. There were also significant changes on the three DPG measures of vasodilatation: peak amplitude increased, the dicrotic index decreased, and peak amplitude on the differentiated DPG increased. A weak correlation was found between the changes in systolic blood pressure and changes in the two measures of DPG peak amplitude. It is concluded that dilevalol is effective in the treatment of hypertension and that DPG is a sensitive noninvasive method to measure vasodilatation. PMID- 1638578 TI - Randomized, prospective comparison of cefoxitin and gentamicin-clindamycin in the treatment of acute colonic diverticulitis. AB - In a randomized, prospective study, single-drug antibiotic therapy with cefoxitin (CFX) was compared to combination therapy with gentamicin and clindamycin (G/C) as definitive treatment for acute colonic diverticulitis. Excluding individuals requiring immediate operation, 51 patients with a clinical diagnosis of diverticulitis, who were hospitalized at five different medical centers, were randomized to receive CFX (30 patients) or G/C (21 patients). Age, sex, and the severity of diverticulitis were similar in the two groups. The cure rates of 90% and 85.7% observed for CFX and G/C, respectively, did not differ significantly. Leukocytosis resolved in a shorter time period in patients treated with CFX than in those treated with G/C (2.5 +/- 0.4 vs 4.1 +/- 0.6 days, respectively) (P = 0.03, Student's t test, unpaired data). Two cases of possibly antibiotic-related toxicity occurred in the CFX group versus three cases in the G/C group. The average cost of a course of CFX therapy was $417 compared with $488 for G/C. In this study, cefoxitin demonstrated efficacy and tolerability similar to that of gentamicin-clindamycin in the treatment of acute colonic diverticulitis and may be preferred in view of its narrower antimicrobial spectrum and lower cost. PMID- 1638580 TI - Efficacy and tolerability of lovastatin in hypercholesterolemic women. AB - In a previous report of a multicenter study (Kannel et al, 1990), the results of 6 months' treatment with lovastatin in 489 adults with primary hypercholesterolemia were presented. The present report contains the results from the 236 women patients. The intial dose of lovastatin was 20 mg daily and could be increased to a maximum of 80 mg/day. At the end of 1 month of treatment, levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, very-low density lipoprotein cholesterol, triglycerides, and the total cholesterol:high density lipoprotein (HDL) cholesterol and LDL:HDL cholesterol ratios were significantly lower and the HDL cholesterol levels were significantly higher. These improvements in the lipid profile were maintained for 6 months. The results in the 88 women aged 65 to 83 years and in the 147 women aged 25 to 64 years were similar. LDL-cholesterol goals of less than 3.36 mmol/L in patients with coronary heart disease (CHD) or two or more CHD risk factors and less than 4.14 mmol/L among the other patients were achieved by 48% of the women at 1 month and 58% by 6 months. At least one adverse effect was reported by 18% of the women, the most common being abdominal pain, diarrhea, and constipation. The results indicate that hypercholesterolemic women respond well to treatment with lovastatin. PMID- 1638581 TI - Effects of ulinastatin, an antiprotease, on alloxan-induced lung injury in dogs. AB - To determine if alloxan-induced lung injury could be prevented by an antiprotease, ulinastatin, we used three groups of five anesthetized, ventilated dogs. They were given saline (20 ml/kg/hr) infusion alone (saline group), alloxan (75 mg/kg) + saline infusion (alloxan group), or ulinastatin (50,000 U/kg) + alloxan + saline infusion (ulinastatin group). The course of all dogs was followed for three hours. In the saline group, extravascular lung water to blood free dry weight (Qwl/dQl) was 3.22 +/- 0.31 g/g (mean +/- SE). The alloxan group presented the following significant findings: a decrease in white blood cell and platelet counts (44.2% and 68.2% of control, respectively) at five minutes; an increase in thromboxane B2 and 6-keto-prostaglandin F1 alpha (731.6% and 476.6% of control, respectively) at 15 minutes; an increase in beta-glucuronidase (124.8% of control) at 30 minutes; and an increase in Qwl/dQl (8.84 +/- 1.82 g/g) at the end of experiment. The addition of ulinastatin significantly reduced most alloxan-induced effects: differences in white blood cell counts, thromboxane B2, 6-keto-prostaglandin F1 alpha, and Qwl/dQl between the saline and ulinastatin groups were small. We conclude that ulinastatin significantly reduces the extent of lung water accumulation in alloxan-induced lung injury. PMID- 1638582 TI - Conversion from glipizide to glyburide: a prospective cost-impact survey. AB - Despite extensive clinical experience with second-generation oral hypoglycemic agents, the relative dosing equivalence of glyburide and glipizide remains controversial. A prospective survey was conducted to determine the feasibility and cost of converting noninsulin-dependent diabetic patients from glipizide to glyburide. A total of 211 patients previously stabilized on glipizide were converted to glyburide and returned to their respective clinics at least once during the following six months. The mean daily dose (+/- SD) of glipizide before conversion was 18.7 +/- 12.32 mg; the mean daily dose of glyburide after seven months was 9.9 +/- 6.52 mg (P less than 0.001, paired t test). Glyburide was well tolerated. The conversion program appeared to be successful and resulted in a 47% reduction in the mean daily dose after conversion from glipizide to glyburide, which, in turn, conferred a 43% savings in the projected yearly expenditures for second-generation oral hypoglycemics. PMID- 1638583 TI - Amoxicillin/clavulanate therapy of respiratory tract infections: a microbiologic perspective. AB - The development of beta-lactamase-producing strains of the common respiratory tract pathogens Hemophilus influenzae and Moraxella catarrhalis has caused increasing resistance to a number of antimicrobial agents, including ampicillin and amoxicillin, that are traditionally used to treat respiratory tract infections. Because antimicrobial therapy for upper and lower respiratory tract infections is usually empiric, an understanding of beta-lactamase-mediated resistance and its implications for antibiotic therapy is critical for the successful treatment of these infections. PMID- 1638584 TI - Treatment of Alzheimer-type dementia with intravenous mecobalamin. AB - The efficacy of intravenous mecobalamin in the treatment of Alzheimer-type dementia was evaluated in ten patients using several rating scales. Vitamin B12 levels and unsaturated binding capacities were also measured and compared to the evaluated intellectual function scores. Mecobalamin was shown to improve intellectual functions, such as memory, emotional functions, and communication with other people. Improvements in cognitive functions were relatively constant when the vitamin B12 levels in the cerebrospinal fluid were high. Improvements in communication functions were seen when a certain level of vitamin B12 was maintained for a longer period. There were no side effects attributable to mecobalamin. We conclude that mecobalamin is a safe and effective treatment for psychiatric disorders in patients with Alzheimer-type dementia. PMID- 1638585 TI - Comparison of two transdermal nitroglycerin systems: Transderm-Nitro and Nitro Dur. AB - Sixty-four patients with stable angina pectoris were enrolled in a four-week, multicenter, office-based study to compare the adhesive properties of an patients' preferences for two transdermal nitroglycerin systems, Transderm-Nitro (TDN) and Nitro-Dur (ND). Each patient simultaneously wore one 0.2 mg/hr (formerly 5 mg/24 hr) TDN patch and one 0.2 mg/hr ND patch. At the first and last study visits, patients completed questionnaires that assessed preferences based on ease of application, handling, and removal; ease of removing the backing; overall adhesion; adhesion under certain conditions; comfort; curling or rolling; and skin irritation. Each day of the study, patients recorded the number of anginal episodes experienced, frequency of sublingual nitroglycerin use, patch adhesion, and problems at the sites of application or any other medical problems. Differences in adhesive properties were statistically significant in favor of TDN over ND (P less than or equal to 0.001). Of the TDN patches, 98.5% adhered completely, compared with 81.8% of the ND patches. No serious or unexpected adverse reactions occurred. Overall, patients preferred TDN to ND by a statistically significant margin (P = 0.0002). PMID- 1638586 TI - Ofloxacin versus trimethoprim/sulfamethoxazole in the treatment of uncomplicated urinary tract infection. AB - A multicenter randomized study was conducted to compare the efficacy and safety of ofloxacin with that of trimethoprim/sulfamethoxazole (TMP/SMX) in the treatment of uncomplicated urinary tract infection in adults. Patients were randomized to receive either oral ofloxacin 200 mg daily for three days (102 patients), or oral TMP/SMX 160 mg/800 mg twice daily for seven days (100 patients). The pathogen was eradicated in 73 (97.3%) of the 75 evaluable patients receiving ofloxacin and in 66 (97.1%) of the 68 evaluable patients receiving TMP/SMX. The most frequently isolated pathogens were Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. More urinary pathogens were susceptible to ofloxacin than to TMP/SMX, although this difference was not statistically significant. The clinical cure rate for patients receiving ofloxacin was 93.3%, with 4% improved and 2.7% failed. For patients receiving TMP/SMX, the clinical cure rate was 86.4%, with 12.1% improved and 1.5% failed. Side effects were reported by 29.7% of the patients receiving ofloxacin and by 40.4% of the patients receiving TMP/SMX. Drug-related adverse experiences, as determined by the investigators, occurred in 5% of the ofloxacin patients and in 15.2% of the TMP/SMX patients, a statistically significant difference. No patients receiving ofloxacin, compared with three patients receiving TMP/SMX, discontinued therapy because of an adverse reaction. These results indicate that short-course ofloxacin is as effective as TMP/SMX in the treatment of uncomplicated urinary tract infection. Ofloxacin therapy is also better tolerated than TMP/SMX. PMID- 1638587 TI - Cefprozil versus cefaclor in the treatment of mild to moderate skin and skin structure infections. The Cefprozil Multicenter Study Group. AB - In a multicenter study, 598 patients with skin or skin-structure infections were randomly assigned to receive 500 mg of cefprozil once daily (or 20 mg/kg once daily) or 250 mg of cefaclor three times daily (or 20 mg/kg daily in three equal doses) for 5 to 10 days. Treatment was evaluated in 212 cefprozil-treated patients and in 210 cefaclor-treated patients. The patients were aged 2 to 99 years (mean, 28 years) and their primary diagnoses were impetigo (in 99 patients), pyoderma (in 98), superficial abscess (in 70), and cellulitis (in 64). A satisfactory clinical response was found in 93% of the cefprozil-treated patients and in 92% of the cefaclor-treated patients, the pathogens were eradicated in 91% and 89%, and overall treatment was rated effective in 87% of both groups. Adverse clinical events were reported by 5% of the patients in both groups; one cefprozil-treated patient and three cefaclor-treated patients withdrew from treatment because of adverse events. It is concluded that cefprozil administered once daily is as effective and safe as cefaclor administered three times daily in the treatment of mild to moderate skin and skin-structure infections. PMID- 1638588 TI - Efficacy of cefaclor AF in the treatment of skin and skin-structure infections. AB - Cefaclor advanced formulation (cefaclor AF) was compared with cefaclor for the treatment of skin and skin-structure infections in a double-blind study at 28 centers in North America. Of the 563 patients originally randomized, 278 patients received cefaclor AF (375 mg twice daily) and 285 patients received cefaclor (250 mg three times daily). A total of 154 patients treated with cefaclor AF and 157 patients treated with cefaclor qualified for the efficacy analysis after completing 7 days of therapy. At the post-therapy visit, favorable clinical response rates for evaluable patients were 97.4% in the cefaclor AF group and 94.9% in the cefaclor group; favorable bacteriologic response rates were 85.7% and 84.1%, respectively. At the late post-therapy evaluation, 7 to 14 days after completion of therapy, favorable clinical response rates were 90.1% in the cefaclor AF group versus 89.9% in the cefaclor group, and favorable bacteriologic response rates were 88.7% and 86.9%, respectively. No significant difference was seen between the groups in clinical or bacteriologic efficacy at either evaluation or in the frequency of nature of side effects reported during the study. PMID- 1638589 TI - Milestones in clinical pharmacology. From experimental to clinical pharmacokinetics. PMID- 1638590 TI - Guidelines for pharmacoeconomic studies. PMID- 1638591 TI - [The role and importance of ambulatory monitoring of blood pressure in the diagnosis, control and therapy of hypertension]. AB - For the diagnosis, control and treatment of hypertension for non-invasive assessment of the blood pressure at present a combination of three methods is used. Clinical assessment (by a physician in the surgery or in bed in bedridden patients) is the basic approach, if necessary supplemented by assessment at home and/or ambulatory monitoring of the blood pressure. Twenty-four-hour ambulatory monitoring can provide representative blood pressure readings. It furnishes information which cannot be obtained in another way; if correctly indicated and the results are used in practice, it is effective and economical. It permits evaluation of the blood pressure response to physical and emotional activity in the course of the day, to assess changes of blood pressure during sleep and to define the prognosis of the disease more accurately. It makes it possible to establish a correct indication of medicamentous therapy, selection of effective drugs and correct timing of the doses. In the submitted paper the authors describe also the limitations of the method as well as possible complications during implementation. Long-term monitoring of the blood pressure should resolve special problems in selected groups of patients. In indicated cases it should be available also in this country and introduced to an appropriate extent also in selected departments concerned with hypertensiology. PMID- 1638592 TI - [Membrane transport of cations in erythrocytes during treatment of essential hypertension with angiotensin-converting enzyme inhibitors]. AB - The authors investigated in ten patients with essential hypertension changes in the membrane transport of sodium in red blood cells and the intracellular calcium content of thrombocytes during the control period during treatment of hypertension with central sympatholytics and after three-week treatment with an inhibitor of the angiotensin converting enzyme (ACE), enalapril. The effect of enalapril in hypertonic patients was manifested by a rise of the renin plasma activity and the potassium concentration and a reduction of the sodium plasma concentration which corresponds to the inhibition of angiotensin II. The intracellular calcium and sodium content was unaltered. In 8 of 10 patients after enalapril treatment increased values of Vmax for Na(+)-K+ cotransport occurred, incl. 6 patients where at the same time a rise of Vmax Na(+)-Li+ countertransport was recorded. PMID- 1638593 TI - [The effect of inactivity on bone mineralization]. AB - In a group of 88 patients, immobile for various reasons a markedly reduced bone mineralization was found, significantly more in patients with denervation of the muscles. As to laboratory indicators, the author recorded a significantly reduced serum calcium level which correlated positively with the mineralization level; there was an insignificantly elevated alkaline phosphatase activity and calciuria. After comprehensive calcium treatment with small doses of vitamin D, and in patients without signs of osteomalacia also with sodium fluoride raised also significantly the serum calcium level, while there was a decline of the alkaline phosphatase activity and a slight increase of calciuria. The fundamental requirement of therapy is burdening of the bones by graded mobilization of the patients. The following series proved useful: isometric contraction of muscles in a recumbent position--standing up, assisted next to the bed--moving round the bed -active rehabilitation. PMID- 1638594 TI - [Culture of skin grafts in vitro]. AB - The paper deals with utilization of skin grafts generated in vitro in treatment of burns, skin ulcers and other defects. Specific properties of autografts, allografts and composite skin substitutes are discussed. The cultivation of keratinocytes, which were successfully applied as autografts in treatment of burn wounds in Kosice, is described in detail. PMID- 1638595 TI - [Long-term prognosis in chronic primary glomerulonephritis in relation to urinary findings]. AB - A long-term followed-up group of 993 patients with primary glomerulonephritis (GN) was divided by urinary syndromes, defined according to the degrees of proteinuria and haematuria. Responding morphological diagnoses and prognoses were found for each urinary syndrome. Isolated and predominant haematuria were determined as benign, with stationary course even without immunosuppressive therapy. The prognosis of isolated, even moderate, proteinuria is more serious finding. Its relevance increases with the degree of haematuria. Severe combined proteinuria and haematuria is the most serious urinary syndrome. Both proteinuria and haematuria may be changing in the course of GN and increasing proteinuria points to the future glomerular filtration rate decrease. PMID- 1638596 TI - [Composite carcinoma-carcinoid of the large intestine]. AB - The authors give an account of a bioptically revealed adenocarcinoma of the large bowel which was combined with a carcinoid. The carcinoid constituent of the tumor had massive metastases as revealed by the postmortem examination. PMID- 1638597 TI - [The significance of antioxidants in pathologic states]. AB - Based on a review of the literature the authors discuss problems of antioxidants which are recently in the foreground of interest of human medicine. In the first part of the paper the authors discuss the importance of antioxidation enzymes and other antioxidants, their correlation with the life span and possibilities of their use in experimental therapy of diseases. The second part of the paper is devoted to the evaluation of antioxidation activity in pathological conditions and the use of antioxidants in the prevention and therapy of various diseases. PMID- 1638598 TI - [How should treatment of esophageal varices proceed?]. AB - The authors submit their experience and data from the literature on the problem of oesophageal varices. In haemorrhage of varices at present the most successful procedure is endoscopic haemostasis concurrently with intensive treatment focused on the basic disease and replacement of blood losses. In patients with a history of haemorrhage from varices endoscopic sclerotization is generally recommended. The authors supplement it with the promising medicamentous reduction of the portal pressure. Other procedures, i.e. surgery, are indicated only in a minority of patients whose varices do not reposed to haemostasis and medicamentous reduction of high portal pressure. The problem how to proceed in varices which did not bleed so far is still unresolved. The authors recommend individual evaluation and submit their own procedure. PMID- 1638599 TI - [Significance of the detection of the familial carcinoma syndrome (Lynch I and II) in the early diagnosis of colorectal carcinoma]. AB - In 1982-1991 at the Fourth Medical Clinic 309 asymptomatic family members meeting the criteria of the hereditary form of colorectal carcinoma (Lynch syndrome- syndrome of familial cancer, also "non-polypous" hereditary colorectal carcinoma) which differs from familial polyposis (adenomatosis) of the colon. The syndrome is characterized by autosomal dominant heredity and by familial incidence of colorectal carcinoma (Lynch I) or colorectal carcinoma and carcinoma of other, in particular gynaecological areas (Lynch II) and a younger age of the affected subjects, a more frequent localization in the right colon, synchronous and metachronous neoplasia. In the authors group 34% were type I, the remainder type II. Initial total coloscopy revealed carcinoma in 51 subjects (78% in the right colon), adenomatous polyps in 99 (73% in the right colon). The mean age of the patients with carcinoma was 47.5 years, of those with adenoma 46.5 years. The majority of cases were recorded in subjects with three or more than three direct relatives with carcinoma (highest risk grade). During subsequent coloscopic check up examinations at intervals depending on individual risk, colorectal carcinoma was detected in another six subjects. In 30 patients it was carcinoma Dukes A, in 12 B and in 3 Dukes C. These results indicate that identification of asymptomatic cases of Lynch syndromes via the family-history and coloscopic follow-up contributes to the early diagnosis of colorectal carcinoma. PMID- 1638600 TI - [Results of studies of indicators of hemostasis in hemodialyzed patients during administration of 1-deamino-8-D-arginine vasopressin]. AB - The fibrinolytic activity (FA) evaluated according to the euglobulin clot lysis time was in haemodialyzed patients (3.0 +/- 0.2 arb. u.) lower than in patients with chronic renal failure treated by conservative methods (4.7 +/- 0.6, p less than 0.05) and than in healthy subjects (4.2 +/- 0.4, p less than 0.05). After stimulation by intravenous administration of 1-deamino-8-D-arginine vasopressin the FA in haemodialyzed patients rose to (4.5 +/- 1.6), less than in conservatively treated (14.1 +/- 2.1, p = 0.06) and than in healthy subjects (18.2 +/- 3.9, p less than 0.001). By using specific methods it was proved that the inadequate rise of FA in haemodialyzed patients after stimulation is conditioned by a defect of the release of the plasminogen tissue activator from the vascular wall. Contrary to healthy subjects (7.0 +/- 1.3 vs. 16.7 +/- 2.3 ng/ml, p less than 0.01) is plasma concentration in haemodialyzed subjects (5.3 +/- 0.5 vs. 7.9 +/- 0.8, NS) did not increase significantly. Repeated examinations of some of the haemodialyzed patients revealed that almost 20 months of regular haemodialysis do not lead to further changes of basal (2.9 +/- 0.3 vs. 2.8 +/- 0.2) nor stimulated (4.2 +/- 0.5 vs. 4.8 +/- 0.9) FA. Basal plasma concentrations of the von Willebrand factor were in the dialyzed patients (89.1 +/- 8.8%) higher than in healthy subjects (67.2 +/- 4.4, p less than 0.05). After stimulation the concentration of the von Willebrand factor increased significantly in healthy subjects (99.1 +/- 4.3, p less than 0.01), but not in dialyzed patients (82.9 +/- 3.1, NS), obviously due to the pathological reactivity of their vascular wall. The above findings may be associated with thromboses and atherosclerosis in patients on long-term dialysis. PMID- 1638602 TI - [Folk healing causing severe diabetic coma]. AB - The authors demonstrate on the case of a 21-year-old female diabetic (type I), who had been well compensated with insulin for five years, the life threatening procedure of a popular healer. By eliminating insulin he induced severe keto acidotic coma. PMID- 1638601 TI - [Could the Czech King Ladislav Pohrobek have had hypophosphatemic osteomalacia caused by a neoplastic disease?]. AB - Histological examination of undecalcified specimens from different parts of skeletal remnants of king Ladislaus revealed a considerable degree of demineralization of a similar type as found in osteomalacia. This fact along with the finding of multiple osteolytic foci in different parts of the skeleton, and consistent with reports of the clinical picture of the disease made the authors present the hypothesis according to which the king may have suffered from so called oncogenic osteomalacia. This bone disease may develop as a complication of some neoplastic disease incl. haemoblastoses and haemoblastomas. The authors think that with regard to the age of the king, historical reports and the multiplicity of osteolytic lesions that the most plausible hypothesis is that of oncogenic osteomalacia associated with some type of malignant non-Hodgkin lymphoma. PMID- 1638603 TI - [Alternative versus scientific medicine]. PMID- 1638604 TI - [Prof. Jan Horbaczewski. On the 50th anniversary of his death]. PMID- 1638605 TI - [Diseases of civilization from the aspect of evolution of the human diet]. AB - The authors discuss contemporary views regarding the causes of diseases of civilization which developed on an epidemic scale in industrial societies during the last 60-70 years. They are due to the immense changes of lifestyle adopted by these societies. On the whole this lifestyle is a marked deviation from optimal conditions for humans. The genetic equipment of man which determines the evolutional advantages and function of different metabolic processes which ensure the homeostasis of the healthy organism is conservative and is entirely adapted to the human genome which developed in the course of hundreds of thousands of years. The aim of preventive medicine is to analyze, point out and enforce diminution of the effect of risk factors, as an important way towards improvement of the general health status of the population. PMID- 1638606 TI - [New recommendations for nutritional requirements for the Czechoslovak population]. AB - The authors present new recommended energy and nutrient allowances for the population of CSFR. The allowances are defined for 29 physiological groups, incl. 11 groups of children and adolescents and 18 groups of adults (productive age and more advanced age groups). The recommended allowances are the result of research of two teams--a Czech and a Slovak one--, results are published in the world literature, FAO and WHO reports. The recommended system can be considered an important step in the area of nutritional prevention of cardiovascular diseases, diabetes and obesity. PMID- 1638607 TI - [Atherosclerotic changes in the carotid artery detected by ultrasound in newly diagnosed type II diabetics]. AB - In a group of 107 middle-aged men with newly detected diabetes type II the authors investigated by means of a double ultrasonographic examination the incidence of atherosclerotic changes of the carotid artery. The incidence of atherosclerotic lesions on the carotid artery was relatively high (44% of the group), the majority of arterial stenoses was, however, without haemodynamic impact. A frequent finding were calcifications in the sclerotic plaques. Affection of the carotid artery was significantly frequently associated with ischaemic heart disease and ischaemia of the lower extremities. As compared with the results of examinations of the lipoprotein and carbohydrate metabolism, the authors found in men with affected carotid arteries as compared with not affected subjects significantly higher triacylglycerol levels, higher levels of circulating insulin and a higher ratio of total to HDL cholesterol. PMID- 1638608 TI - [Treatment of diabetic retinopathy using panretinal laser coagulation]. AB - The author presents an account of his experience with panretinal photocoagulation by means of greenish-blue light of an argon laser in diabetics. He evaluates the technique of treatment. In a group of 156 eyes of 103 patients 1-18 months after photocoagulation with a mean follow-up period of nine months the author compares the development of visual acuity after treatment. Based on these findings he describes the success and asset of treatment for the patient. After one year in 62% of 63 investigated eyes deterioration of visual acuity was arrested, in 16% improvement was achieved. After one and a half year 64% of 33 followed up patients were stabilized, in 12% the visual acuity was still better than at the onset of treatment. Panretinal photocoagulation by means of an argon laser can be considered at present the most effective treatment of diabetic retinopathy. PMID- 1638609 TI - [Botulinum toxin in the treatment of blepharospasm. Initial experience]. AB - The clinical effects of botulinum toxin A were evaluated in eight patients with idiopathic blepharospasm and hemifacial spasm. A substantial reduction or disappearance of muscle spasms were observed after the treatment. The action of botulinum toxin became noticeable 2 days after administration with a peak effect at 2 weeks. This effect diminished with muscle spasms returning about 12 weeks after administration. No serious adverse events were noted. The treatment with botulinum toxin has become method of choice in blepharospasm, it is proposed for the management of local muscle spasms of various origin. PMID- 1638610 TI - [The medical history of a small town]. PMID- 1638611 TI - [Nutritional recommendations for adults with diabetes mellitus according to the Czech Diabetology Society]. PMID- 1638612 TI - [Development of indications for cesarean section in the Czech Republic and certain developed countries]. AB - The author analyzes the reasons for the rapid increase of pregnancies terminated by caesarean section; in some countries (USA, Canada and others) the frequency is as high as 20%. The main reason was a change of indication for caesarean section: not only hazard to the mother, but above all hazard to the foetus. It seems however that there is no relationship between the frequency of caesarean and the level of perinatal mortality. On the contrary, in many instances caesarean section increases the risk of mother and foetus and the neonate. In the Czech Republic the rate of caesarean sections was 7.8%: the main indications were the hazard of foetal hypoxia and an unfavourable presentation of the foetus. Some non obstetric indications play a part: in particular orthopaedic and ophthalmological ones: they are the indication for every tenth caesarean section. In multiple pregnancies (in our country 42% are terminated by caesarean section), in particular pathological presentations of the foetus are involved. So far efforts of the international obstetric organization to reduce the use of caesarean section did not prove very successful. PMID- 1638613 TI - [Characteristics of the regulation of blood circulation in patients with heart transplants]. AB - The author gives an account and conclusions of investigations pertaining to the circulation in patients with a transplanted heart. Attention is focused on the problem of the central and peripheral circulation, systemic hypertension and electrophysiology. The conclusions of these clinical and experimental observations reveal new findings and pathophysiological relations which contribute to the spread of basic knowledge on the circulation in patients with a transplanted heart and may serve as a starting point for seeking their prevention and therapy. PMID- 1638614 TI - [Mental therapy of headache]. AB - In a group of patients with headache the authors found that mental therapy was very effective. It produced a better effect than previous therapeutic procedures. The authors discuss contemporary views of mechanisms of modern pharmacotherapy of headache and draw attention to its hazards, economic pretentiousness and frequently low availability. The authors mention also non-pharmacological methods used nowadays in the therapy of headache and their relationship to the endogenous opioid system. They explain mental therapy as the interaction and energy exchange between the aura of the emitor and percipient of the mental energy. The authors expressed the hypothetical idea on the basis of analgetic action of mental therapy. They recommend to extend research of mental energy in medical disciplines--theoretical and clinical--and to introduce mental therapy into practice on a professional level. Based on their own experience the authors decided to apply it already now where it gives hope of recovery or mitigation of the patients' suffering. They consider it their duty. PMID- 1638615 TI - [The first cases of transmission of tularemia in Southern Moravia]. AB - The authors described two cases of the ulceroglandular form of tularaemia where the infection was transmitted to man after a sting by a tick in the Brno area. The incubation period was two weeks and 11 days resp., the course of the disease, in particular in the female patient was relatively severe and complicated, obviously due to the late establishment of the diagnosis and thus delayed aetiological treatment. The authors recommend to consider a tularaemic aetiology in case of a febrile disease which develops within two weeks after a tick sting, in particular if the site of the prick becomes inflamed and regional lymphadenitis develops. PMID- 1638616 TI - [Creatine phosphate as a drug in acute myocardial infarct]. AB - The reserves of endogenous creatine phosphate are very rapidly exhausted in ischaemia. This leads at first to reversible and later to irreversible cell damage. Creatine phosphate can be administered in the preparation Neoton. It serves not only as a source of energy after arrest of oxidative phosphorylation; its main effect is stabilization of sarcolemma and protection against its disintegration. Several publications provide evidence of its favourable effect on the protection of the heart muscle during operations on the open heart, on a reduced incidence of ventricular arrhythmias in acute myocardial infarction and improvement in chronic cardiac insufficiencies. In Czechoslovakia multicentre clinical studies are under way testing Neoton in cardiological indications. PMID- 1638617 TI - [Principles of specimen collection and information which can be derived from a cytological examination]. PMID- 1638618 TI - [Jan Amos Komensky--still with us]. PMID- 1638619 TI - [Endoscopic "perestrojka"]. AB - The authors discuss in a brief review the mighty development of invasive endoscopy in the next few years. Based on their own findings as well as data in the literature, they assume that it will be necessary to prepare theoretical as well as practical material for this quite newly developing discipline. It penetrates already at present to all European surgical and gastroenterological departments and changes fundamentally the approach to diagnosis and treatment of diseases of the gastrointestinal tract. PMID- 1638620 TI - [Spinal cord tumors and tumors causing spinal cord compression in the aged]. AB - In incipient disorders of gait in old people frequently the possible presence of a benign spinal tumour is not taken into account. The patients are treated for assumed common complaints associated with old age. Thus much valuable time is lost before the only correct approach--surgery--is made. The author describes in her own group of patients early symptoms of spinal compression and supplements data by case-histories. The results of surgery in a group of patients with benign spinal tumours depended on the degree of spinal compression as well as on the duration of this compression. In the group of epidural secondary spinal tumours the results of surgery were not satisfactory. PMID- 1638621 TI - [Incidence of cholecystolithiasis in a population 20-59 years of age]. AB - In 1989-1990 sonographic examination of the gallbladder of 1186 people aged 20-59 years revealed in 262 cholecystolithiasis (22.1%). The group comprised 477 men (40.2%) and 709 women (59.8%). The general prevalence which is 22.1% comprises prevalence of sonographically revealed lithiasis--213 patients (18%) and lithiasis treated by cholecystectomy before sonographic examination--49 patients (4.1%). Among men cholecystolithiasis was revealed in 60 (12.6%) and among women in 202 (28.5%). The author discusses the relationship of cholecystolithiasis and body weight and the incidence of the disease in the family. PMID- 1638622 TI - [Increased acid phosphatase in isolated transitory hyperphosphatasemia]. AB - In a 13-month-old girl with typical signs of isolated transient hyperphosphatasaemia the authors found repeatedly elevated acid phosphatase values. This finding supports the hypothesis of a temporary increase of bone remodelling in this condition. PMID- 1638623 TI - [Training and specialization of physicians in the Federal Republic of Germany]. PMID- 1638624 TI - [Purkinje's role in obtaining the Comenian from the Lesny archives]. PMID- 1638625 TI - [Evolution in biology--yes or no? Thoughts on the 400th anniversary of the birth of J.A. Comenius]. PMID- 1638626 TI - [Recommendations for the prevention of atherosclerosis and ischemic heart disease. Detection and treatment of persons with increased lipids in adulthood]. PMID- 1638627 TI - One rotten apple spoils the whole bushel: the role of ethylene in fruit ripening. PMID- 1638628 TI - Bacterial plasmids and gene flux. PMID- 1638629 TI - corkscrew encodes a putative protein tyrosine phosphatase that functions to transduce the terminal signal from the receptor tyrosine kinase torso. AB - We describe the characterization of the Drosophila gene, corkscrew (csw), which is maternally required for normal determination of cell fates at the termini of the embryo. Determination of terminal cell fates is mediated by a signal transduction pathway that involves a receptor tyrosine kinase, torso, a serine/threonine kinase, D-raf, and the transcription factors, tailless and huckebein. Double mutant and cellular analyses between csw, torso, D-raf, and tailless indicate that csw acts downstream of torso and in concert with D-raf to positively transduce the torso signal via tailless, to downstream terminal genes. The csw gene encodes a putative nonreceptor protein tyrosine phosphatase covalently linked to two N-terminal SH2 domains, which is similar to the mammalian PTP1C protein. PMID- 1638630 TI - Genetic isolation of ADA2: a potential transcriptional adaptor required for function of certain acidic activation domains. AB - We have devised a genetic strategy to isolate the target of acidic activation domains of transcriptional activators based on toxicity in yeast cells of the chimeric activator, GAL4-VP16. Toxicity required the integrity of both the VP16 acidic activation domain and the GAL4 DNA-binding domain, suggesting that inhibition resulted from trapping of general transcription factors at genomic sites. Mutations that break the interaction between GAL4-VP16 and general factors would alleviate toxicity and identify transcriptional adaptors, if adaptors bridged the interaction between activators and general factors. We thus identified ADA1, ADA2, and ADA3. Mutations in ADA2 reduced the activity of GAL4 VP16 and GCN4 in vivo. ada2 mutant extracts exhibited normal basal transcription, but were defective in responding to GAL4-VP16, GCN4, or the dA:dT activator. Strikingly, the mutant extract responded like wild type to GAL4-HAP4. We conclude that ADA2 potentiates the activity of one class of acidic activation domain but not a second class. PMID- 1638631 TI - Sorting of protein A to the staphylococcal cell wall. AB - The cell wall of gram-positive bacteria can be thought of as representing a unique cell compartment, which contains anchored surface proteins that require specific sorting signals. Some biologically important products are anchored in this way, including protein A and fibronectin binding protein of Staphylococcus aureus and streptococcal M protein. Studies of staphylococcal protein A and Escherichia coli alkaline phosphatase show that the signal both necessary and sufficient for cell wall anchoring consists of an LPXTGX motif, a C-terminal hydrophobic domain, and a charged tail. These sequence elements are conserved in many surface proteins from different gram-positive bacteria. We propose the existence of a hitherto undescribed sorting mechanism that positions proteins on the surface of gram-positive bacteria. PMID- 1638632 TI - Identification of a neural alpha-catenin as a key regulator of cadherin function and multicellular organization. AB - The function of cadherin cell adhesion molecules is thought to be regulated by a group of cytoplasmic proteins, including alpha-catenin. We identified a subtype of alpha-catenin, termed alpha N-catenin, which is associated with N-cadherin and expressed mainly in the nervous system. cDNA transfection experiments showed that alpha N-catenin can also bind with E-cadherin. To investigate the role of alpha N catenin, we transfected lung carcinoma PC9 cells, which express E-cadherin and beta-catenin but neither alpha- nor alpha N-catenin, with alpha N-catenin cDNA. While parental PC9 grew as isolated cells, the transfectant lines formed aggregates in which cells were tightly adhered to each other, showing epithelial arrangements, and they occasionally gave rise to cystic spheres. These results suggest that alpha N-catenin is crucial not only for cadherin function but also for organization of multicellular structures. PMID- 1638633 TI - A transcription factor with SH2 and SH3 domains is directly activated by an interferon alpha-induced cytoplasmic protein tyrosine kinase(s). AB - Interferon-stimulated gene factor 3 (ISGF3), the primary transcription factor induced by interferon alpha, is a complex of four (113, 91, 84, and 48 kd) proteins. This paper reports that the 113, 91, and 84 kd (ISGF3 alpha) proteins of ISGF3 contain conserved SH2 and SH3 domains. A specific interferon alpha induced cytoplasmic protein tyrosine kinase(s) can form a transient complex with ISGF3 alpha proteins. These ISGF3 alpha proteins can be immunoprecipitated by anti-phosphotyrosine antibodies only after interferon alpha treatment. Phosphoamino acid analyses of 32P-labeled ISGF3 alpha proteins confirm that ISGF3 alpha proteins are directly tyrosine phosphorylated both in vitro and in vivo in response to interferon alpha, and this tyrosine phosphorylation can be inhibited by staurosporine and genistein. Phosphatase treatment of these ISGF3 alpha proteins results in inhibition of ISGF3 complex formation in vitro. These observations indicate that interferon alpha-induced direct tyrosine phosphorylation of ISGF3 alpha proteins is necessary for activation of the transcription factor ISGF3. PMID- 1638634 TI - A cDNA encoding a pRB-binding protein with properties of the transcription factor E2F. AB - The retinoblastoma protein (pRB) plays an important role in the control of cell proliferation, apparently by binding to and regulating cellular transcription factors such as E2F. Here we describe the characterization of a cDNA clone that encodes a protein with properties of E2F. This clone, RBP3, was identified by the ability of its gene product to interact with pRB. RBP3 bound to pRB both in vitro and in vivo, and this binding was competed by viral proteins known to disrupt pRB E2F association. RBP3 bound to E2F recognition sequences in a sequence-specific manner. Furthermore, transient expression of RBP3 caused a 10-fold transactivation of the adenovirus E2 promoter, and this transactivation was dependent on the E2F recognition sequences. These properties suggest that RBP3 encodes E2F, or an E2F-like protein. PMID- 1638636 TI - Epidemiology of tendon injuries in sports. AB - During the last few decades, the role of sports and physical activity has become more and more important in all modern communities. Conditioning sports are generally considered positive by many governments because of their beneficial effect on human well-being. The risk of injury is increased, for both acute traumas and overuse injuries, and prevention has also become more important in sports. Epidemiologic studies are important when planning prevention programs for sports injuries. Because of individual sport cultures and different sport habits in different countries, national epidemiologic studies are of importance in each individual country. PMID- 1638635 TI - Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F like properties. AB - An expression vector was modified to permit the rapid synthesis of purified, 32P labeled, glutathione S-transferase (GST)-retinoblastoma (RB) fusion proteins. The products were used to screen lambda gt11 expression libraries, from which we cloned a cDNA encoding a polypeptide (RBAP-1) capable of binding directly to a putative functional domain (the pocket) of the retinoblastoma gene product (RB). The RB "pocket" is known to bind, directly or indirectly, to the cellular transcription factor, E2F, implicated in cell growth control. We have found that RBAP-1 copurifies with E2F, interacts specifically with the adenovirus E4 ORF 6/7 protein, binds specifically and directly to a known E2F DNA recognition sequence, and contains a functional tranasactivation domain. Therefore, RBAP-1 is a species of E2F and can bind specifically to the RB pocket. PMID- 1638637 TI - Tendinitis I: basic concepts. PMID- 1638638 TI - Functional anatomy and physiology of tendons. AB - Tendons vary in type, shape, and size. The anatomy, histology, and physiology of tendons are described in this article, with particular reference to those tendons that are vulnerable in sports medicine. PMID- 1638639 TI - Biomechanical loading of Achilles tendon during normal locomotion. AB - Direct in vivo Achilles tendon force measurements open up new possibilities for understanding the loading of the Achilles tendon during natural locomotion. This article describes how these human experiments can be performed. The results of these experiments imply that Achilles tendon forces are unexpectedly high in certain activities (e.g., hopping) and that the rates of loading rather than the absolute magnitudes of the recorded forces may be more relevant for clinical purposes as well as for the construction of artificial tendon materials. PMID- 1638640 TI - Cell-matrix response in tendon injury. AB - The healing response after tendon injury is defined by cell matrix adaptive capability. There are distinct macrotraumatic and microtraumatic injury patterns and a spectrum of pathologic responses from inflammation to tissue degeneration, as characterized by the tendinosis phenomenon. Epigenetic and genetic factors govern recovery from tendon injury. The potential for future modulation of injury repair by protein mediators or growth factors appears promising. PMID- 1638641 TI - Radiologic evaluation of tendon injuries. AB - This article reviews the imaging choices available to assess the tendons of the shoulder, knee, ankle, and wrist. Principles of tendon imaging and fundamental considerations of computer-derived image techniques are briefly discussed, with particular reference to magnetic resonance imaging. Although the criteria used to classify various tendon abnormalities are provided, the clinical role of imaging is emphasized. PMID- 1638642 TI - The use of eccentric training and stretching in the treatment and prevention of tendon injuries. AB - Tendon injuries are a common consequence of either sports or daily routine activity. Most people will suffer at least one tendon injury in his or her lifetime. It is therefore prudent to understand the different ways to load tendon and the ways in which the muscle-tendon-bone unit responds to these stresses. By maximizing tendon training and rehabilitation, one can maximize the stresses (eccentric) a tendon will withstand. This article provides an explanation of these principles. PMID- 1638643 TI - Medical modifiers of sports injury. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in sports soft-tissue injury. AB - This article provides a background for the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in sports medicine, including the nature of the drugs, the settings and rationale for their use, and concerns about their general safety. The criteria for the ideal study to examine the efficacy and safety of NSAIDs after acute injury is then enumerated, including a review of how many of the published studies have met each of the major criteria. Selected studies are described to demonstrate those that have or have not provided the basis for a rational decision on the use of NSAIDs in sports medicine and in the treatment of tendinitis. Finally, this article draws conclusions based on these published studies. PMID- 1638644 TI - Physical modalities in the treatment of tendon injuries. AB - Physical modalities such as heat, cold, and electricity have been used for many years in the treatment of tendon injuries. This article examines the basic modalities that the athletic trainer and physical therapist use in these treatment programs and how well they have performed. The indications and contraindications for both are included. PMID- 1638646 TI - [Treatment of dilated cardiomyopathy in childhood]. AB - Authors reviewed available information concerning etiology and pathophysiology of dilated cardiomyopathy. Diagnostic criteria and current poor results of conservative treatment are discussed. Between August 1984 and August 1991 67 children with various types of cardiomyopathy underwent heart and heart and lung transplantation at Harefield Hospital, U.K. Dilated cardiomyopathy was the indication for transplantation in 47 patients (mean age at operation was 6.5 years, range 0.3-4.8 years). Eighty-one percent actuarial survival at 4 years after operation represents reasonable progress in the treatment of this severe acquired disease. Currently, early transplantation is recommended in children with dilated cardiomyopathy and with low shortening fraction of left ventricle (below 0.13), without any improvement after 3 months of conservative treatment, will familial trait of dilated cardiomyopathy and/or with severe myocardial fibrosis. PMID- 1638647 TI - [Normal values of 2-dimensional echocardiographic parameters in children]. AB - The authors examined by two-dimensional echocardiography a group of 186 healthy children from birth to the age of 18 years. From the assembled records they measured the following: the inner diameter of the inferior vena cava, the diameter of the abdominal aorta, the area of the right and left atrium at the end of systole, the width of the ring of the tricuspid and mitral valve at the end of diastole, the area of the right and left ventricle at the end of systole and its circumference, the width of the annulus of the pulmonary artery, the diameter of the aortic arch, the diameter of the right and left branch of the pulmonary artery. The systolic function of the left ventricle and the curvature of the ventricular septum during systole was calculated from the assessed parameters of the left ventricle. By means of a computer the regression equations of the relation of assessed echocardiographic parameters and body weight and body surface were calculated as well as their mean values +/- 2 standard deviations for the given body weight and body surface which are considered normal for the child population. PMID- 1638645 TI - Principles of rehabilitation after chronic tendon injuries. AB - This article describes a framework for the evaluation, diagnosis, and management of tendon injuries that result from repetitive microtrauma overload. These injuries are commonly called tendinitis injuries, but are more often degenerative lesions. The initial management of acute tendon injuries with rupture is usually quite different than that of chronic injuries, but the functional rehabilitation of the acute injuries can follow the same framework. PMID- 1638648 TI - [Treatment of a patent duct in neonates]. AB - The authors analyze clinical and laboratory aspects of Indomethacin treatment of neonates with a patent ductus arteriosus. From June 1987 to November 1990 the authors treated 19 neonates with a patent ductus arteriosus with Indomethacin. The drug was administered, 0.1-0.3 mg/kg body weight, by the oral route three times/24 or 36 hours. In 17 infants after Indomethacin treatment the duct closed, in two infants the duct did not close during Indomethacin treatment, in three infants the authors observed oliguria which improved after discontinuation of treatment. PMID- 1638649 TI - [Personal experience with the use of human recombinant erythropoietin in the treatment of anemia in children with chronic renal insufficiency]. AB - The authors analyze the course of treatment with human recombinant erythropoietin (rHuEPO) in five children in the preterminal stage of chronic renal insufficiency and one premature infant with a low birth weight and anaemia and acute renal insufficiency. rHuEPO was administered, 50-100 u./kg, by the s.c. route 2-3X per week. During the first month of treatment the haemoglobin rose from 7.0 dag/l to 8.2 dag/l and persisted at this level approximately to the third month of treatment. The haematocrit reached values of 0.30 during the 4th month of therapy when the authors observed also the maximum increase of reticulocytes (20%). The authors did not find a marked decline of iron and ferritin concentrations. In the child with a low birth weight treatment with rHuEPO was started at the age of six weeks and the age haemogram was favourably influenced already after four weeks of treatment with rHuEPO. PMID- 1638650 TI - [Prevention of post-exertion airway obstruction in children and adolescents with bronchial asthma]. AB - In 86 asthmatics (age 8-16 years), divided into several groups, the protective effects of pharmacological and non-pharmacological agents on the exercise-induced airway obstruction (e.i.a.o.) by 5 minutes free running were studied. There were studied the preventive inhalations of bronchodilators, i.e. fenoterol (0.2 mg), ipratropium-bromide (0.06 mg) and both combined of 0.15 mg of fenoterol and 0.06 mg of ipratropium-bromide on the exercise-induced airway obstruction. The protective effects of breathing through nose as well as the effect of the temperature in the surrounding environment on the e.i.a.o. were studied too. The exercise-induced airway obstruction was assessed on the basis of parameters measured from maximum expiratory flow-volume curves. Maximum expiratory flow at 25% of vital capacity was most sensitive in the assessment of e.i.a.o. The studied bronchodilators protected all patients against e.i.a.o. The textile face mask (surgical mask) put on the nose and mouth during 5 min. free running outdoors and in a closed room protected some asthmatics completely against e.i.a.o. or reduced substantially e.i.a.o. in others. The nose breathing had a similar effect on e.i.a.o. as the textile face mask. The surrounding temperature of air was not decisive in the induction of post-exercise airway obstruction. Non pharmacological agents ought to be thus more included among the therapeutical means in pediatric and adolescent asthmatics. PMID- 1638651 TI - [Hypertrophy of neonates in diabetic mothers and their long-term prognosis]. AB - Hundred and seventy five infants of diabetic mother born and followed up carefully in the Institute for the Care of Mother and Child were examined at a mean age of 20.75 +/- 4.08 years. The purpose of the investigation was to assess the relationship of hypertrophy of neonates of diabetic mothers to other deviations in neonates and their long-term prognosis. In neonates with a marked degree of hypertrophy the authors recorded significantly more frequently hypoglycaemia, early asphyctic syndrome, impaired respiration and neurological symptoms. Children born as hypertrophic developed equally frequently diabetes (8.7%) as children of diabetic mothers who did not develop hypertrophy (8.0%). Abnormal glucose tolerance was recorded in those with hypertrophy in 6.6%, in the group without hypertrophy in 5.0%. As compared with the offspring of healthy mothers, they suffered significantly more frequently from higher blood sugar levels and higher insulinaemia (sigma C ad sigma I) during the oGTT. The body weight expressed as BMI and systolic blood pressure were also higher than in the control group. None of the investigated indicators in adult age was associated with body weight and the degree of hypertrophy. The development of diabetes is determined more by genetic factors. PMID- 1638652 TI - [A/B type behavior in relation to changes in the ocular background in juvenile diabetics]. AB - Within a broadly conceived interdisciplinary project pertaining to some specific problems of the psychology of health (preventive psychology) attention was focused also on an analysis of interrelations of A/B type of behaviour and juvenile diabetes. The methodological basis were the results, reported in the work of Skorodensky, Kralikova et al in 1988 in the Journal Cs. Pediatrie (1). The results of this work confirmed that the Hunter-Wolf scale (for more details of the scale see ref. 1) relevantly divided the group of somatically healthy children into type A and B and that its retrospective discriminating capacity is adequate as regards biochemical, physiological and anthropometric values (specified as risk factors of IHD in adults). Children in Part A of the scale tended to have a higher score of the above risk factors, leading later in adult age to the development of IHD. Obviously only longitudinal perspective research of a selected sample of children can confirm definitely or rule out this assumption. PMID- 1638653 TI - [Eczema herpeticum in children: clinical picture and therapy]. AB - The authors submit information on the course and therapeutic experience with acyclovir (Zovirax Wellcome Co. and Herpesin Lachema Co.) in 67 children with eczema herpeticatum (EH) who were hospitalized at the Clinic of Infectious Child Diseases in Brno from January 1983 to January 1991. In all instances treatment led to rapid drying of the herpetis eruptions, a shorter period of new eruption and rapid improvement of the serious clinical condition. In none of the children visceral dissemination of the virus of herpes simplex (HSV) were occurred and in none of the children toxic side-effects were found. The authors confirmed the assumed identical course of EH after i. v. administration of acyclovir of foreign or local origin. After i.v. administration frequently dramatic improvement of the general and local finding was recorded, as compared with oral administration. There were no therapeutic differences in the clinical effects of tablets and suspension, the clinical effect being comparable. PMID- 1638654 TI - [Histochemical findings in the atrioventricular conduction system in congenital heart defects]. AB - The authors examined, using histochemical methods, the AV conduction system in five infants and two children who died unexpectedly with a congenital heart disease. The activity of "glycogen dependent" phosphorylase in the AV conduction system was mostly negative or weak. The probable cause of this finding is hypoxia, although the effect of hypotrophy must be admitted. In groups of cells penetrating into connective septal tissue a decrease of oxidoreductases and hydrolases was found. These findings may be associated with regressive changes in the postnatal reduction of the AV conduction system. PMID- 1638655 TI - [Hypophosphatasia--one of the causes of congenital rickets]. PMID- 1638656 TI - [Recommendations for the Prague population on behavior during smog conditions]. PMID- 1638657 TI - [The Jindrichuv Hradec model of a clinic for pediatric pneumonology. 2. Results]. PMID- 1638658 TI - Insecticide-impregnated bed nets for malaria control: a review of the field trials. AB - Insecticide-impregnated bed nets act as a physical barrier to repel and kill mosquitos. Community intervention trials suggest that these nets are effective in preventing malaria-related mortality and morbidity--but not malaria infection--in areas of low and moderate transmission; the results from areas of high transmission are not so encouraging. Comparison of the results from these trials and their interpretation are difficult because of variations in the epidemiology of malaria and several methodological flaws. Problems such as defining appropriate health indicators, monitoring bed-net usage, introducing bed nets randomly, selecting adequate controls, performing statistical analysis, and comparing bed nets with other available interventions are considered. Further community intervention trials are needed, paying attention to the methods and to assessment of their impact on malaria. PMID- 1638659 TI - A low-cost, community-based measles outbreak investigation with follow-up action. AB - An outbreak of measles in Kampala, Uganda, in 1990 raised concern about the effectiveness of the measles vaccine that was used. The Uganda EPI programme and the medical office of the Kampala City Council therefore conducted a community based investigation, with door-to-door interviews in two selected communities. They revealed 68 measles cases ranging in age from 5 months to 12 years; the highest age-specific attack rate (32%) was found in children aged 12 to 23 months. BCG immunization coverage was high (85%), but measles immunization coverage was moderate (48%). One community, served by a mobile clinic, presented a vaccine efficacy of only 55%. Responses by mothers revealed that many had failed to have their children completely immunized because of a lack of information, and not because of difficulties in access to the service. In a follow-up, community leaders initiated monthly checking of immunization cards of both children and mothers. The low vaccine efficacy found in one of the communities resulted in a thorough assessment of the city's cold chain. This community-based approach proved to be cost-effective and practical for identifying the obstacles to effective immunization delivery. PMID- 1638660 TI - Detection of HIV-1 antibodies in blood specimens spotted on filter-paper. AB - Described are the results of an international collaborative study to evaluate the use of whole blood samples spotted on filter-paper (BSP) for the detection of antibodies to human immunodeficiency virus type 1 (HIV-1). BSP samples were collected from 40 patients at risk for HIV-1 infection and tested blindly using commercially available HIV antibody test kits, either specifically manufactured or modified for this purpose. Parallel serum samples were also collected, and the antibody reactivity was defined and confirmed by Western blot. The results demonstrate that recovery of antibodies from BSP samples after elution can be comparable to that from serum. Some kits can be easily adapted to test BSP samples, while others cannot. At present, detection of HIV antibodies in BSP samples should therefore be carried out using kits specifically manufactured for this purpose or by the development of a modified protocol using a panel of BSP and their corresponding serum specimens. PMID- 1638661 TI - Missed opportunities for immunization during visits for curative care: a randomized cross-over trial in Sudan. AB - Infants who come to health facilities for curative care in developing countries are usually not vaccinated at the same time. To assess what could be done a randomized cross-over study was carried out in twelve urban health centres in Sudan where two approaches were investigated: (1) the place for vaccination was moved very close to the consulting room, and (2) the doctor seeing the infant wrote a prescription recommending vaccination for the child. On average, 55% of the infants needing immunization were vaccinated when either of these approaches was followed. No difference was found between the two interventions in terms of the proportion of eligible children who were immunized (mean difference, 2%; 95% Cl, -4% to +7%). The more sick an infant appeared to be to the mother, the more likely she was to refuse vaccination. Older infants and infants not previously vaccinated were also less likely to be immunized. The number of missed opportunities can thus be reduced using these simple approaches. However, to immunize infants who are sick, unvaccinated, or have limited access to health facilities will require more social mobilization, health education, and outreach activities. PMID- 1638662 TI - Ten years of kala-azar in west Bengal, Part I. Did post-kala-azar dermal leishmaniasis initiate the outbreak in 24-Parganas? AB - Following resurgence in Bihar of epidemic kala-azar, outbreaks of the disease were identified simultaneously in two separate foci about 500 km apart in West Bengal in 1980. While the outbreak in one of these foci, in northern West Bengal, was the result of a direct extension of the Bihar epidemic, the source of parasite in the other (in the village of Bandipur in the south of West Bengal) remained unknown until a case of nodulo-ulcerative post-kala-azar dermal leishmaniasis (PKDL) was located in the village. The continued presence of this case in the village from a time long before the outbreak aroused strong suspicion about its causal role. Laboratory-bred female Phlebotomus argentipes sandflies were allowed to feed on four cases of PKDL, including the case from Bandipur, to determine the transmission potential of these cases. Of a total of 400 flies in the experiment, 104 (26%) fed on the cases, and of these flies 44 died (31 within 48 hours of feeding). Of the surviving 60 flies, 32 developed promastigotes in the mid-gut. In view of the presence of the case of PKDL in the village prior to the outbreak and the availability of a susceptible human population and vectors, it is possible that the patient with PKDL was a source of Leishmania donovani parasites for the local focus. Furthermore, PKDL may act as a reservoir of parasites during inter-epidemic periods. PMID- 1638663 TI - Factors influencing the response to chemotherapy in human cystic echinococcosis. AB - As the effectiveness of mebendazole and albendazole in patients with echinococcosis has been found to vary, we investigated some of the factors likely to be responsible. A total of 79 patients who were treated with mebendazole (44 patients) or albendazole (35 patients) were included in the study. Evaluation of the treatment results was based on the changes in cyst morphology, as evidenced by the results of X-ray radiography, sonography, and computed tomography, and on analysis of the findings in relation to parasitic and drug factors. The response of cysts according to their site did not vary much, with the exception of the poor response of bone cysts. A more important factor seems to be cyst size, since the treatment was more efficacious against smaller and younger cysts. The presence of daughter cysts should be regarded as an unfavourable factor for treatment response. Cyst multiplicity did not present insurmountable difficulties, provided the cysts were small and a prolonged course of therapy was undergone. The choice of drug used for the therapy was important, with the results supporting the advantage of albendazole. In planning the chemotherapy of hydatid disease, factors such as cyst condition and drug used should therefore be taken into consideration. PMID- 1638664 TI - [Comparative study of 3 bacteriological tests of cerebrospinal meningitis during the epidemiological period]. AB - During an outbreak of group A meningococcal meningitis in Chad in 1988, a comparative study of three bacteriological techniques (direct microscopic examination, latex agglutination, and culture) was conducted with 120 samples of cerebrospinal fluid (CSF) for diagnosis. The results correlated well with cloudy or purulent CSF specimens. Direct microscopic examination was as good a diagnostic indicator as the other tests. The authors recommend using direct microscopic examination, which is easy to perform under field conditions and accurate enough for a rapid diagnosis of cerebrospinal meningitis during an epidemic. However, complete identification of the first cases in the epidemic is important in order to establish control measures as soon as possible. PMID- 1638665 TI - Susceptibility of Plasmodium falciparum strains to mefloquine in an urban area in Senegal. AB - A total of 47 nonimmune febrile patients from Pikine, Senegal, with greater than 1,000 Plasmodium falciparum asexual forms per microliter whole blood were given 12.5 mg per kg body weight of mefloquine in a single oral dose and were followed up daily until day 7 and also on day 14 of the study. Seven of the patients who vomited, four who had 4-aminoquinolines in their blood, and five dropouts were excluded. Fever and parasitaemia were suppressed within four days until day fourteen in 29 of the 31 remaining patients, including 10 with P. falciparum strains that had a low sensitivity to mefloquine. Two failures were due to poor absorption of mefloquine. The presence of P. falciparum strains with low in vitro susceptibility to mefloquine did not affect, within 14 days, the clinical and parasitological efficacy of a single oral dose mefloquine regimen in patients who had received no previous antimalarial treatment and who did not have partial immune protection. PMID- 1638666 TI - Epidemiology of blindness and visual impairment in Vanuatu. AB - A population-based survey of blindness was conducted in Vanuatu. Data were gathered on a sample of 3520 of the approximately 150,000 inhabitants of Vanuatu aged at least 6 years, in order to estimate the prevalence and causes of blindness among the whole population. An overall prevalence of blindness of 4.0 per 1000 was found, 85% of which was due to cataract, an avoidable cause of this disability. PMID- 1638668 TI - Public health actions and nuclear emergencies. PMID- 1638667 TI - Health care utilization patterns in developing countries: role of the technology environment in "deriving" the demand for health care. AB - Health care services, in combination with several intermediate (proximate) determinants of health such as environmental sanitation and nutrition, directly influence health status. In the economics literature, this is referred to as the health production technology. Although many studies recognize that demand for health care depends on the health production technology, otherwise known as a "derived" demand, this review indicates that few of them have so far been able to fully incorporate this technology in estimating significant determinants of health care use. Understanding the technology environment could help explain why substantial portions of the population do not gain access to care even when financial factors do not appear to be a barrier. Also, low utilization of health services may simply reflect the low productivity of these services when other complementary factors such as nutrition or clean water and sanitation are lacking. Finally, since health-producing technology is often a multistep (multivisit) process, health care demand studies generally offer an incomplete picture of health care utilization patterns because they focus on a single event such as the first visit of an illness episode. Researchers should obtain more complete information on the interaction between all health production inputs, their availability and access to them. Multidisciplinary methodologies are likely to be useful. PMID- 1638669 TI - Expanded programme on immunization for the 1990s. PMID- 1638670 TI - Human biomonitoring and the 32P-postlabeling assay. PMID- 1638671 TI - Phorone (diisopropylidene acetone), a glutathione depletor, decreases rat glucocorticoid receptor binding in vivo. AB - The exact mechanism by which carcinogens and tumor promoters act on the glucocorticoid receptor system in vivo is not known. Based on earlier studies that sulfhydryl-reducing agents stabilize glucocorticoid receptor binding in vitro, some workers have postulated that endogenous reducing factors may be important for glucocorticoid receptor function in vivo. To test whether glutathione (GSH) may serve this purpose, we investigated the effects of phorone, an agent that partially depletes intracellular GSH, on the hepatic cytosolic glucocorticoid receptor (GRc) binding characteristics in intact and 7-10 day adrenalectomized (ADX) adult female Sprague-Dawley rats. Biochemical analysis revealed that a single treatment of phorone (300 mg/kg) to both intact and ADX rats significantly decreased the liver GSH concentration (70-90% of control levels) as well as the GRc maximum binding concentration (30% of control levels). The decrease in GSH levels preceded the reduction in GRc maximum binding concentrations; both effects were reversible after 24 h of treatment. The phorone mediated decrease of GSH levels was maximum at doses greater than 75 mg/kg, whereas GRc maximum binding concentrations in vivo appeared dose dependent up to 400 mg/kg. Pretreatment with phorone or the carcinogens mirex and 3 methylcholanthrene significantly decreases GRc binding and nuclear uptake in vivo, as well as diminishes intracellular cytosolic GSH levels. Although a temporal relationship between the GSH levels and the GRc maximum binding concentrations in vivo was observed, there was no quantitative relationship between these two parameters based on our phorone dose-response and the carcinogen pretreatment data. Our findings suggest that during the early phases of carcinogenesis, the hepatocellular GSH does not play a direct role upon the biochemical action of certain carcinogens and tumor promoters on the glucocorticoid receptor binding in the liver. PMID- 1638672 TI - Acetoxime is metabolized by human and rodent hepatic cytochrome P450 enzymes to the genotoxicant and carcinogen propane 2-nitronate. AB - The hepatocarcinogenicity of acetoxime has been tentatively linked with its metabolic oxidation to the potent genotoxicant and carcinogen propane 2-nitronate (P2-N). In order to test the hypothesis that acetoxime is metabolized to P2-N, the oxime (20 mM) was incubated with liver microsomes from mice, rats and two humans. Ion-pair HPLC analysis of the incubates afforded a peak that co-eluted with P2-N. P2-N exists in tautomeric equilibrium with 2-nitropropane (2-NP). Samples of the microsomal incubates, which had been adjusted to pH 5.5 and kept for 24 h in order to allow maximal tautomeric equilibration of P2-N to 2-NP to occur, were extracted with hexane. GLC analysis of the extracts yielded a peak that co-eluted with 2-NP, and gave a mass spectrum identical to that of authentic 2-NP. The metabolite peak obtained on HPLC was isolated and its hexane extract contained also 2-NP when investigated by GLC. P2-N was found by HPLC in the urine of rats that had received acetoxime (3.36 mmol/kg i.p.). Hexane extracts of urine samples, which had been adjusted to pH 5.5 and left for 24 h, contained 2-NP as demonstrated by GLC analysis. The results are consistent with the suggestion that the toxicity of acetoxime is associated with its biotransformation to P2-N. PMID- 1638673 TI - Chromosome aberrations following cytotoxic therapy in patients in complete remission from lymphoma. AB - The frequency of chromosome aberrations in the peripheral blood of patients successfully treated for Hodgkin's disease (HD) and non-Hodgkin's lymphoma is compared with that seen in age-matched haematologically normal subjects. Findings are considered in relation to risk factors associated with the development of secondary myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML). Overall aberration frequencies were not significantly increased in patients compared with normal subjects. However, there were differences in aberration type. The frequency of exchanges was significantly higher among patients (P less than 0.01) and the frequency of gaps lower (P less than 0.0005). The mean frequency of exchanges was also greater in patients receiving multiple compared to single courses of therapy (P less than 0.0005) and in patients receiving radiotherapy or combined modality therapy compared to chemotherapy alone (P less than 0.005 and P less than 0.0005). Four patients had aberration frequencies greater than 2 SD above the patient mean. One of these was also found to have a mutation of the ras oncogene. None of the patients has yet developed secondary MDS/AML. PMID- 1638674 TI - Systemic and local carcinogenesis by directly acting N-nitroso compounds given to rats by intravesicular administration. AB - A number of directly acting carcinogenic N-nitroso compounds were administered to female F344 rats intravesically, to assess their ability to induce tumors locally in the urinary bladder and systemically following absorption through the bladder mucosa. The compounds were alkylnitosoureas and alkylnitrosocarbamates and could be formed by interaction of amides with bacterially produced nitrite in infected bladders. Methylnitrosourethane was very toxic: doses of 1-2 mg caused death of some rats. A total dose of 0.15 mmol of ethylnitrosourethane, which was much less toxic, was administered to each rat and almost all developed bladder tumors. Ethylnitrosourea also gave rise to bladder tumors following intravesical treatment, and induced some tumors systemically, whereas methylnitrosourea, 2 methoxyethylnitrosourea and 2-hydroxypropylnitrosourea induced bladder tumors in high incidence and few tumors systemically. Nitrosooxazolidone was quite toxic and induced few bladder tumors. The dialkylnitrosoureas were more stable and some induced more tumors systemically than the monoalkylnitrosoureas. 1,3 Dimethylnitrosourea induced no bladder tumors and 1,3-diethylnitrosourea very few, but both induced tumors systemically that were similar to those induced by gavage treatment of rats. 1-Ethyl-1-nitroso-3-hydroxyethylurea, 1-hydroxyethyl-1 nitroso-3-ethylurea and 1-(2-hydroxypropyl)-1-nitroso-3-(2-chloroethyl)-urea induced bladder tumors in a majority of rats treated intravesically; the first induced many tumors systemically. Most of the bladder tumors were transitional cell papillomas and carcinomas, but there were a few squamous cell tumors, smooth muscle tumors, sarcomas and carcinosarcomas. The effects of intravesical administration of the directly acting alkylating compounds are compared with the effects of similar doses given to rats by gavage. PMID- 1638675 TI - Inhibition of cellular transformation by triphenylmethane: a novel chemopreventive agent. AB - Triphenylmethane (TPM) was found to inhibit 3-methyl-cholanthrene-induced neoplastic transformation of 10T1/2 cells in a dose-dependent manner (ED50 = 2.8 microM). This activity was independent of any effect on intercellular communication and did not appear to be directly related to the general antioxidant properties of TPM as measured by cellular thiobarbituric acid reactive substances. Triphenylmethanol (TPMOL) and diphenylmethane also inhibited transformation (ED50 = 6.9 and 90 microM respectively). TPM had no effect on the proliferation of exponentially growing cells. At higher concentrations TPM and its analogues enhanced plating efficiency of cells indicating no significant toxicity for these compounds at levels up to 50 microM. The inhibitory effects of TPM on transformation were reversible when TPM was removed from the medium. While TPM had no effect on the growth of fully transformed cell lines, it was able to inhibit the growth of 1/3 neoplastic foci in the presence (but not absence) of 10T1/2 cells. TPM was found to stimulate protein kinase C (PKC) activity for both crude C3H10T1/2 cytosolic PKC and purified PKC obtained from rat brain. The ability of TPM to stimulate PKC activity appeared to be dependent on [CaCl2] and the order of reagent addition in the assay. Tamoxifen, a structurally related compound to TPM, was also found to enhance PKC activity over the same concentration range but was less potent than TPM. The biological effects of TPM and related compounds indicate that they function in a manner distinct from other highly unsaturated transformation inhibitors such as carotenoids and retinoids. The inability of triphenylene to inhibit transformation suggests that a reactive methyl carbon may be essential for activity. PMID- 1638676 TI - Alterations in protein kinase C isozymes alpha and beta 2 in activated Ha-ras containing papillomas in the absence of an increase in diacylglycerol. AB - The levels of protein kinase C (PKC) activity, PKC isozymes, as well as the level of endogenous diacylglycerols (DAG) were examined in early emergence mouse skin papillomas and compared to the levels in the epidermis. The papillomas were derived from a two-stage carcinogenesis protocol in which mice were initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and promoted twice weekly for only 12 weeks with 12-O-tetradecanoylphorbol-13-acetate (TPA). As expected, greater than 90% of these early emergence papillomas contained an activated Ha-ras gene with an A----T transversion in the 61st codon. There was a TPA-independent, irreversible decrease in total PKC activity (70%) in the early emergence papillomas compared to that in the epidermis. Immunoblot analysis of epidermis and papillomas taken 4 weeks following the cessation of TPA treatment, a time when PKC catalytic activity has completely recovered to control level in epidermis but not in papillomas, revealed that the levels of PKC-alpha and PKC beta 2 were dramatically decreased in the cytosol of the papillomas, while the levels of these two isozymes in the particulate fraction were approximately equal to the epidermis. PKC-delta, -epsilon and -zeta immunoreactive proteins were present in both epidermis and papillomas and only minor changes were observed in the papillomas. PKC-delta and PKC-epsilon displayed a particulate fraction localization in both the epidermis and papillomas, while PKC-zeta was found in both subcellular fractions. We were unable to detect PKC-gamma in mouse epidermis or papillomas. Since the level of DAG has been shown to be elevated in some ras transformed cells, we examined DAG levels in the papillomas, as an increased DAG level could explain the constitutive decreases in the levels of PKC. Measurements of cellular DAG indicated that there was no elevation in the total pool of DAG in the early emergence papillomas. These data demonstrate an irreversible decrease in and alteration of the subcellular distribution of PKC-alpha and beta 2 in DMBA initiated/TPA-promoted papillomas. These changes are TPA-independent, and occur in the absence of an elevation in the total pool of endogenous DAG. These alterations of PKC isozymes may be important early events in multistage tumorigenesis. PMID- 1638677 TI - Inhibition of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-DNA binding by chlorophyllin: studies of enzyme inhibition and molecular complex formation. AB - Chlorophyllin (CHL), a copper/sodium salt of chlorophyll used in the treatment of geriatric patients, is an anti-mutagen that has been demonstrated to inhibit carcinogen--DNA binding in vivo. To study the mechanism of inhibition, the microsomal metabolism of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and the kinetics of IQ--DNA binding were investigated in the presence and absence of CHL. In time-course studies, CHL produced greater than 80% inhibition of IQ--DNA binding and blocked the metabolism of IQ, such that 80% of the initial dose of carcinogen was recovered unmetabolized from the incubations after 1 h. Kinetic constants were determined for the in vitro DNA binding reaction, with the reaction rate measured as 'pmol IQ bound/mg DNA/min/mg microsomal protein'. Without altering V(max), the Km of the IQ--DNA binding reaction was increased by CHL, and the replot of Km/V(max) versus CHL concentration yielded a straight line with an inhibitor constant of 58.3 microM CHL. Spectrophotometric studies provided evidence in vitro for the formation of a non-covalent complex between CHL and IQ. The CHL--IQ complex had a stoichiometric ratio of 2:1 (mole ratio method) and an apparent dissociation constant from the Benesi-Hilderbrand plot of 1.41 x 10(-4)M at pH 7.4. These results are discussed in the context of a CHL inhibitory mechanism involving enzyme inhibition and molecular complex formation. PMID- 1638678 TI - Detection and characterization by 32P-postlabelling of DNA adducts induced by a Fenton-type oxygen radical-generating system. AB - Reactive oxygen species can give rise to numerous modifications of DNA. We have investigated the formation of such modifications using the nuclease P1 digestion method of the 32P-postlabelling procedure for the detection of DNA damage. Analysis of DNA that had been treated with a Fenton-type system of copper (or iron) ions and H2O2 resulted in the detection of up to ten discrete 32P-labelled spots, displaying chromatographic characteristics similar to aromatic adducts, on PEI-cellulose TLC. Maximum total levels equivalent to 28 adducts/10(8) nucleotides were achieved after 15 min of treatment with Cu2+/H2O2. The formation of adducts was 1.5 times greater if single-stranded rather than double-stranded DNA was employed, suggesting an intrastrand effect. Experiments with 3' deoxyribonucleotides demonstrated that the adducts detected did not represent base modifications such as 8-hydroxydeoxyguanosine or thymidine glycols. However, treatment of specific dinucleotides (dApdG and dApdA) was found to produce two major adducts that were chromatographically identical by TLC and HPLC to the two major adducts formed in DNA. It is proposed that these species with aromatic adduct-like characteristics are the result of the intrastrand linking of specific adjacent bases in DNA. PMID- 1638679 TI - Role of DNA repair in malignant neoplastic transformation of human mammary epithelial cells in culture. AB - Epithelial cells derived from normal human mammary tissue were examined for capacity to repair radiation-induced chromatin DNA damage. Repair capacity was estimated by quantifying chromatid aberrations in metaphase cells arrested 0.5 1.5 h after X-irradiation during G2. The parental cells at passage 12 had 19 chromatid breaks and 16 gaps per 100 metaphase cells, representing efficient repair. Of two continuous cell lines, derived after benzo[a]pyrene treatment, A1 maintained the efficient repair phenotype through passage 50, while a subline of A1 developed the repair-deficient phenotype characterized by a 3- to 5-fold higher frequency of chromatid breaks or gaps. This line was transformed to tumorigenic cells by HaMSV and SV40 T antigen. The second continuous line B5 and derivatives had 102-165 chromatid breaks and 87-134 gaps per 100 metaphases (deficient repair phenotype). This line was transformed to tumorigenic cells by KiMSV. As reported previously for human epidermal keratinocytes, acquisition of this repair-deficient phenotype appears to be an early requisite step in the malignant neoplastic transformation of human cells in culture. PMID- 1638680 TI - Comparison of the biotransformation of 1,3-butadiene and its metabolite, butadiene monoepoxide, by hepatic and pulmonary tissues from humans, rats and mice. AB - 1,3-Butadiene (BD), a widely used monomer in the production of synthetic rubber and other resins, is one of the 189 hazardous air pollutants identified in the 1990 Clean Air Act Amendments. BD induces tumors at multiple organ sites in B6C3F1 mice and Sprague-Dawley rats; mice are much more susceptible to the carcinogenic action of BD than are rats. Previous in vivo studies have indicated higher circulating blood levels of butadiene monoepoxide (BMO), a potential carcinogenic metabolite of BD, in mice compared to rats, suggesting that species differences in the metabolism of BD may be responsible for the observed differences in carcinogenic susceptibility. The metabolic fate of BD in humans is unknown. The objective of these studies was to quantitate in vitro species differences in the oxidation of BD and BMO by cytochrome P450-dependent monooxygenases and the inactivation of BMO by epoxide hydrolases and glutathione S-transferases using microsomal and cytosolic preparations of livers and lungs obtained from Sprague-Dawley rats, B6C3F1 mice and humans. Maximum rates for BD oxidation (Vmax) were highest for mouse liver microsomes (2.6 nmol/mg protein/min) compared to humans (1.2) and rats (0.6). The Vmax for BD oxidation by mouse lung microsomes was similar to that of mouse liver but greater than 10 fold higher than the Vmax for the reaction in human or rat lung microsomes. Correlation analysis revealed that P450 2E1 is the major P450 enzyme responsible for oxidation of BD to BMO. Only mouse liver microsomes displayed quantifiable rates for metabolism of BMO to butadiene diepoxide (Vmax = 0.2 nmol/mg protein/min), a known rodent carcinogen. Human liver microsomes displayed the highest rate of BMO hydrolysis by epoxide hydrolases. The Vmax in human liver microsomes ranged from 9 to 58 nmol/mg protein/min and was at least 2-fold higher than the Vmax observed in mouse and rat liver microsomes. The Vmax for glutathione S-transferase-catalyzed conjugation of BMO with glutathione was highest for mouse liver cytosol (500 nmol/mg protein/min) compared to human (45) or rat (241) liver cytosol. In general, the KMs for the detoxication reactions were 1000-fold higher than the KMs for the oxidation reaction. Because of the low solubility of the BD and the relatively high KM for oxidation, it is likely that the Vmax/KM ratio will be important for BD and BMO metabolism in vivo. In vivo clearance constants were calculated from in vitro data for BD oxidation and BMO oxidation, hydrolysis and GSH conjugation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1638681 TI - Inhibitory effect of calcium chloride on gastric carcinogenesis in rats after treatment with N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride. AB - The effects of calcium chloride on glandular stomach carcinogenesis induced by N methyl-N'-nitro-N-nitrosoguanidine (MNNG) and sodium chloride were investigated in male outbred Wistar rats. Animals were given MNNG solution (100 p.p.m.) as drinking water and simultaneously fed a diet supplemented with 5% sodium chloride for 8 weeks. Matched negative controls received neither MNNG nor sodium chloride. Rats were then fed basal diet and given calcium chloride solution (1 or 0.2%) or tap water for the following 52 weeks. The incidences and multiplicities of preneoplastic hyperplasias in the glandular stomachs of rats given MNNG/sodium chloride followed by 1 and 0.2% calcium chloride were significantly lower than those in rats given MNNG/sodium chloride alone. The inhibitory effects of calcium were exerted in a dose-dependent manner. Calcium treatment also showed a tendency to inhibit the development of gastric adenocarcinomas although this was not statistically significant. Rats without carcinogen treatment had neither carcinomas nor preneoplastic hyperplasias in the glandular stomach. Calcium intake also significantly reduced the levels of malondialdehyde, a measure of lipid peroxidation, in the gastric mucosa and urine, the former in a dose dependent manner. Thus, calcium chloride exerted inhibitory effects when given during the post-initiation phase of two-stage glandular stomach carcinogenesis in rats. PMID- 1638682 TI - Comparison of selenium and sulfur analogs in cancer prevention. AB - Several organoselenium compounds have been shown to have powerful anticarcinogenic activity. In view of certain similarities between selenium and sulfur biochemistry, we have evaluated the chemopreventive efficacy of three pairs of analogs using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor model in rats. The compounds tested were selenocystamine/cysteamine, Semethylselenocysteine/S-methylcysteine, selenobetaine/sulfobetaine. In the first study, each agent was added to the basal AIN-76A diet and was given before and continued after DMBA treatment until the end. All three selenium compounds were active; a 50% inhibition was achieved at approximately 25 x 10(-6) mol/kg with Se methylselenocysteine and selenobetaine and at approximately 40 x 10(-6) mol/kg with selenocystamine. In the sulfur series, only cysteamine and S-methylcysteine produced anticancer activity, and the levels required for comparable responses were 500- to 750-fold higher compared to the corresponding selenium analogs. Sulfobetaine was inactive even when present at near maximally tolerated levels. In the second study, Se-methylselenocysteine and S-methylcysteine were chosen for further examination during the initiation and post-initiation phases of mammary carcinogenesis. Se-Methylselenocysteine was effective when it was given either before or after DMBA administration. In contrast, S-methylcysteine was effective only after DMBA treatment. Thus, compared to the sulfur structural analogs, selenium compounds are much more active in cancer protection and may have a multi modal mechanism in preventing cellular transformation as well as in delaying or inhibiting the expression of malignancy after carcinogen exposure. PMID- 1638683 TI - Effects of ethanol and various alcoholic beverages on the formation of O6 methyldeoxyguanosine from concurrently administered N-nitrosomethylbenzylamine in rats: a dose-response study. AB - Consumption of alcoholic beverages has been identified as a major cause of oesophageal cancer in industrialized countries, with an exceptionally high risk associated with apple-based liquors (calvados). In the present study, we have determined the dose--activity relationship of the effects of coincident ethanol on the formation of O6-methyldeoxyguanosine (O6-MEdG) by the oesophageal carcinogen N-nitrosomethylbenzylamine (NMBzA). Male Fischer 344 rats received a single intragastric dose of NMBzA (2.5 mg/kg body wt; 7.4 ml/kg body wt) in tap water containing 0-20% ethanol (v/v). Survival time was 3 h. In controls, concentrations of O6-MEdG were similar in oesophagus, lung and liver (11-14.9 mumol/mol dG). In oesophagus, coincident ethanol increased levels of O6-MEdG from 15.2 mumol/mol (0.1% ethanol) to 46.0 mumol/mol (20%). This increase was dose dependent for 1-20% ethanol; however, low doses produced a larger effect per gram of ethanol than higher doses. In lung, concentrations of O6-MEdG increased from 11 mumol/mol (0.1%) to a plateau value of 24 mumol/mol (greater than or equal to 5%). In nasal mucosa, an increase in O6-MEdG from 3.9 mumol/mol (controls) to 30.7 mumol/mol was observed with 4% ethanol. Effects of ethanol on hepatic DNA methylation were statistically non-significant. Modulation of NMBzA bioactivation by various alcoholic beverages (adjusted to 4% ethanol) was also investigated. Increases in oesophageal O6-MEdG were similar (+50% to +116%) with pear brandy, rice wine (sake), farm-made calvados, gin, Scotch whisky, white wine, Pilsner beer and aqueous ethanol. Significantly higher increases were elicited by commercially distilled calvados (+125%) and red burgundy (+162%). In contrast to its effects at an ethanol content of 4%, farm-made calvados diluted to 20% ethanol produced significantly higher (+200%) increases in oesophageal DNA methylation than aqueous ethanol (+148%). Our results show that ethanol is an effective modulator of nitrosamine bioactivation in vivo at intake levels equivalent to moderate social drinking, and that some alcoholic beverages contain congeners that amplify the effects of ethanol, suggesting that modulation of nitrosamine metabolism by acute ethanol may play a role in the etiology of human cancer. PMID- 1638684 TI - Variant protein patterns in hepatomas and transformed liver cell lines as determined by high resolution two-dimensional gel electrophoresis (2DE). AB - Deviations in the pattern of soluble proteins from chemically induced primary rat hepatomas and from transformed, tumorigenic liver cell lines were determined by high resolution two-dimensional gel electrophoresis (2DE). As compared with the protein pattern of normal rat liver with approximately 1300 protein spots visible in silver-stained gels, quantitative and qualitative alterations were found in hepatomas including neoexpression of glutathione-S-transferase P, as described earlier. After correction for proliferation-related changes by comparison with gels of cells from regenerating rat liver, 30 protein variants remained, which were identically up- (n = 6) or down-regulated (n = 18) or were detected as new spots (n = 6) in primary hepatomas and transformed tumorigenic liver cell lines which are devoid of contaminating nonparenchymal cells. Seven of these variants showed a reduced expression in short-term cultured liver cells indicating dedifferentiation processes in the transformed state. Several hepatoma- and transformation-associated variants were found in clusters of similar mol. wt and/or pI, among them a complex of eight protein variants at approximately 33 35.5 kDa and a pI of approximately 6.6-7.4. Spots of this cluster show considerable changes between the investigated experimental groups and might be suited for being studied at the level of posttranslational modification during carcinogenesis. PMID- 1638685 TI - Cytotoxic and mutagenic effects of methylnitrosourea in two human fetal fibroblast strains differing in O6-methylguanine-DNA methyltransferase activity. AB - A non-transformed human fibroblast strain, GM11, established from the skin of a therapeutically aborted fetus, has been reported to exhibit the Mer- phenotype, i.e. inability to support the growth of adenovirus 5 damaged with 1-methyl-3 nitro-1-nitrosoguanidine. In the present study we determined (i) loss of colony forming ability and frequency of mutants resistant to 6-thioguanine (6TG) on exposure to the SN1 alkylating agent methylnitrosourea (MNU) and (ii) amount of O6-methylguanine-DNA methyltransferase (MGMT), the protein responsible for repairing O6-methylguanine (O6mG) produced by MNU, in GM11 cells compared to GM10, a Mer+ human fetal fibroblast strain. Irrespective of in vitro culture age, GM10 cells responded normally to the cytotoxic action of the alkylating agent, i.e. their clonogenic survival curves exhibited a shoulder at low MNU concentrations (less than or equal to 0.4 mM) and a D10 (dose reducing survival to 10%) of approximately 1.4 mM. By contrast, no shoulder was observed on the survival curves of GM11 cells and their D10 values decreased from approximately 0.6 mM at passage 4 to 0.1 mM at passage 27. In GM10 (Mer+) cells, unlike the biphasic dose response seen for cell killing, the frequency of 6TG-resistant mutants increased as a linear function of chemical concentration delivered (range 0.05-1.2 mM); the induced mutation frequency in these cells (passage 16-20) was equal to 220 x 10(-6)/mM MNU, a yield some 5-fold greater than that reported by others for non-fetal human fibroblasts. GM11 cells proved to be only approximately 1.5 times more mutable by MNU than GM10 cells at late passage, and the susceptibility of the former strain to MNU-induced mutations did not change significantly as a function of culture age (i.e. 316 x 10(-6) and 326 x 10(-6) mutants/mM MNU at passages 4 and 16-20 respectively). The GM10 strain contained approximately 75,000 MGMT molecules/cell at all passages (4-20) examined, whereas the GM11 strain harbored deficient amounts of the protein (approximately 22,500 molecules/cell) at the lowest passage available (4), and this residual activity decreased precipituously to undetectable amounts by passage 16. Together, these data demonstrate that in the two human fetal strains examined the constitutive level of cellular MGMT activity correlates much better with resistance to reproductive inactivation than with mutagenesis by MNU, implying that inefficient repair of O6meG lesions impacts more severely on cell lethality than on mutation induction in at least some biological systems. PMID- 1638686 TI - Effects of cytochrome P450 inducers on I-compounds in rat liver and kidney DNA. AB - I-compounds are covalent DNA modifications presumably derived from endogenous electrophiles. To investigate the possible role of cytochrome P450 in I-compound metabolism, groups of female Sprague-Dawley rats (225-250 g) were treated i.p. with vehicle or cytochrome P450 inducers, i.e. 80 mg/kg phenobarbital (PB), 20 mg/kg 3-methylcholanthrene (MC) or 50 mg/kg pregnenolone-16 alpha-carbonitrile (PCN), once daily for 4 days. DNA synthesis rate was measured via [3H]methylthymidine incorporation. DNA adducts and I-compounds in liver and kidney were analyzed 1 and 8 days after the last treatment. Total liver and kidney microsomal cytochrome P450 content and activities of representative drug metabolizing enzymes for PB, MC and PCN, i.e. benzphetamine N-demethylase, ethoxycoumarin O-deethylase (ECD) and erythromycin N-demethylase, were also determined in all groups. PCN caused significant depletion of total non-polar I compounds at 1 day, compared to controls. Levels of several individual I-spots in liver were differentially reduced by each of the three inducers at 1 day. Most I spots were restored to control levels at 8 days. Kidney I-compounds were not affected by PB or PCN, but MC reduced the level of one non-polar individual I compound at 1 day. Except for the expected DNA adduct formation from MC, there were no qualitative changes in profiles of postlabeled modified nucleotides. Total cytochrome P450 content in liver microsomes and activities of individual P450 enzymes were significantly increased by treatment with each of the inducers at 1 day. This was, however, not the case at 8 days in PB- and PCN-treated livers. MC-treated rats, on the other hand, displayed elevated levels of liver cytochrome P450 and ECD at 8 days. In kidney, PB and PCN did not elicit induction of P450 and individual enzymes, but MC increased total P450 content and ECD activity at 1 day, and ECD activity alone at 8 days. These results suggest a major role for cytochrome P450 enzymes in the metabolism of I-compounds. PMID- 1638687 TI - NADPH-supported and arachidonic acid-supported metabolism of the enantiomers of trans-7,8-dihydrobenzo[a]pyrene-7,8-diol by human liver microsomal samples. AB - Using a new sensitive reverse-phase HPLC assay relying on UV detection at 344 nm, the capacity of 18 human liver microsomal samples to support NADPH-dependent, cytochrome P450-mediated oxidation and arachidonic acid-dependent oxidation of the enantiomers of trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (B[a]P-7,8-DHD) was determined. The (-)-7R,8R-enantiomer, the preferred substrate of cytochrome P450, formed 94% diolepoxide 2 (anti-isomer; 7R,8S-dihydroxy-9S,10R-epoxy 7,8,9,10-tetrahydrobenzo[a]-pyrene) measured as derived alcohols, and the (+) 7S,8S-enantiomer formed 67% diolepoxide 1 (syn-isomer; 7S,8R-dihydroxy-9S,10R epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene). Arachidonic acid-supported oxidations gave approximately 70% diolepoxide 2 from each enantiomer. The involvement of different sets of cytochrome P450 isozymes was supported by incubations in the presence of alpha-naphthoflavone (alpha-NF) (50 microM) and correlation studies. In the absence of alpha-NF, a positive correlation was found between the metabolism of the (-)-enantiomer but not the (+)-isomer of B[a]P-7,8,-DHD and the relative content of P450IA2. In the presence of alpha-NF, the P450IIIA3/4 content correlated positively with the metabolism of both the (+)-enantiomer and the (-) enantiomer. Gestodene (100 microM) inhibited the alpha-NF-stimulated metabolism, confirming the involvement of cytochrome P450IIIA3/4. No difference was found between the extent of arachidonic acid-supported, peroxyl radical-mediated metabolism of the (+)- and (-)-enantiomers of B[a]P-7,8-DHD. The metabolism was almost completely abolished by 2 microM butylatedhydroxyanisole and 100 microM nordihydroguaiaretic acid, confirming the free radical nature of the reaction. PMID- 1638688 TI - Mechanisms associated with the expression of cisplatin resistance in a human ovarian tumor cell line following exposure to fractionated X-irradiation in vitro. AB - Interactions between cisplatin (CDDP) and irradiation are of potential significance for the combined modality treatment of cancer. Previous data have indicated that following in vitro exposure to X-irradiation certain tumour cells expressed resistance to CDDP. To identify parameters associated with this CDDP resistance, the human ovarian carcinoma cell line SK-OV-3/P was pre-exposed to fractionated X-irradiation (total dose: 50 Gy) in vitro. The resultant subline (SK-OV-3/DKR-10) proved 2-fold resistant to CDDP, but not to acute X-irradiation. Consistent with unaltered dihydrofolate reductase and thymidylate synthase activities, SK-OV-3/DXR-10 cells were neither cross-resistant to methotrexate nor to 5-fluorouracil. Verapamil (6.6 microM) significantly (P less than 0.05) enhanced CDDP-induced cytotoxicity in the resistant DXR-10 subline, but not in the parental cells. Total glutathione levels were significantly (P less than 0.01) lower in the resistant subline and BSO pretreatment failed to influence cytotoxicity, whilst related enzyme activities were not consistently modified in the SK-OV-3/DXR-10 cells. Resistance in these cells was associated with significantly decreased cisplatin uptake (P less than 0.002). Immediately following drug exposure the total platination level of the DNA, quantitated immunochemically, was higher (P less than 0.05) in the resistant subline indicative of increased tolerance to DNA damage. After an 18 h post-treatment incubation the parental cell line appeared proficient in the removal of the intrastrand adduct Pt-AG, but deficient in removing the major adduct Pt-GG and the difunctional Pt-(GMP)2 lesion, whilst the DXR-10 resistant subline appeared proficient in removal of all four Pt-DNA adducts. DNA polymerases alpha and beta activities, however, were comparable in both cell lines. These data implicate both enhanced repair and increased tolerance of DNA damage as mechanisms of resistance to CDDP resulting from in vitro exposure of a human ovarian carcinoma cell line to fractionated X-irradiation. PMID- 1638689 TI - Biological markers of exposure to benzene: S-phenylcysteine in albumin. AB - Results of experiments in our laboratory have shown that benzene is metabolized by animals in part to an intermediate that binds to cysteine groups in hemoglobin to form the adduct S-phenylcysteine (SPC). These results suggested that SPC in hemoglobin may be an effective biological marker for exposure to benzene. However, we could not detect SPC in the globin of humans occupationally exposed to benzene concentrations as high as 28 p.p.m. for 8 h/day, 5 days/week. As another approach, we examined the binding of benzene to cysteine groups of a different blood protein, albumin. To facilitate the process, a new method for the precipitative isolation of albumin from plasma was also developed. The isolated albumin was analyzed for SPC by isotope dilution GC-MS. We used this approach to measure SPC in the albumin of F344/N rats exposed by gavage to 0-10,000 mumol/kg benzene. Amounts of albumin-associated SPC increased as a function of dose, followed by a leveling off in the amount of SPC seen at doses greater than 1000 mumol/kg. Levels of SPC were measured in humans occupationally exposed to average concentrations of 0, 4.4, 8.4 and 23 p.p.m. benzene 8 h/day, 5 days/week. Of nine controls, seven had levels of SPC below the limit of detection (0.1 pmol SPC/mg albumin). SPC increased in the exposed groups linearly, giving a statistically significant slope (P less than 0.001) of 0.044 +/- 0.008 pmol/mg albumin/p.p.m. with an intercept of 0.135 +/- 0.095 pmol/mg albumin. From this study, we conclude that SPC in albumin may prove useful as a biomarker for benzene exposure. PMID- 1638690 TI - 32P-postlabeling analysis of adducts formed from 1-phenylazo-2-hydroxynaphthalene (Sudan I, Solvent Yellow 14) with DNA and homopolydeoxyribonucleotides. AB - A 32P-postlabeling assay was employed for detection and quantitation of DNA adducts formed with carcinogenic 1-phenylazo-2-hydroxynaphthalene (Sudan I, Solvent Yellow 14) activated by a peroxidase system. Enrichment of adducts by digestion with nuclease P1 or by extraction into n-butanol prior to 32P-labeling was used. Both enrichment procedures exhibited comparable results for recovery of individual DNA adduct spots. Co-chromatographic analyses of adduct spots obtained by reaction with DNA and homopolydeoxy-ribonucleotides showed that four out of the eight major Sudan I-DNA adducts were formed by reaction of activated Sudan I with deoxyadenosine or deoxyguanosine in DNA. The accuracy of quantitation of adducts by 32P-postlabeling procedure is discussed. PMID- 1638691 TI - Inhibitory effect of dietary iron deficiency on inductions of putative preneoplastic lesions as well as 8-hydroxydeoxyguanosine in DNA and lipid peroxidation in the livers of rats caused by exposure to a choline-deficient L amino acid defined diet. AB - Effects of dietary iron deficiency on inductions of putative preneoplastic lesions and oxidative alterations in the livers of rats by a choline-deficient L amino acid defined (CDAA) diet were examined. Male Fischer 344 rats, 4 weeks old, were used with a total experimental period of 16 weeks, consisting of 4-week pretreatment and 12-week treatment periods (periods A and B respectively). During period A, a choline-supplemented L-amino acid defined (CSAA) or an iron-deficient CSAA diet was administered, and the CDAA or an iron-deficient CDAA diet was fed in period B. Formation of 8-hydroxydeoxyguanosine (8OHdG), a DNA adduct generated by activated oxygen species, in DNA and lipid peroxidation in liver cell membranes were sequentially determined after the beginning of period B. At the end of the experiment, development of gamma-glutamyltransferase (GGT) and glutathione S-transferase placental form (GSTP) positive liver lesions were quantitatively analysed. In the animals fed the CDAA diet, formation of 8OHdG and lipid peroxidation increased with time, and GGT and GSTP positive liver lesions developed. Formation of 8OHdG, lipid peroxidation and the numbers of induced enzyme-altered liver lesions were all reduced in rats fed the iron-deficient CSAA diet in period A and/or the iron-deficient CDAA diet in period B. The present results indicate that iron plays an important role in induction of preneoplastic liver lesions in rats caused by exposure to the CDAA diet possibly in connection with its known catalytic role in generation of highly reactive activated oxygen species. PMID- 1638692 TI - Role of N-glucuronidation in benzidine-induced bladder cancer in dog. AB - The mechanism by which benzidine induces bladder cancer in dog was evaluated by assessing metabolism of [3H]benzidine by dog liver slices and microsomes. Slices incubated with 0.05 mM [3H]benzidine exhibited a 32.5 min incubated with 0.05 mM [3H]benzidine exhibited a 32.5 min peak, which was also produced when microsomal incubations were supplemented with UDP-glucuronic acid. In contrast to microsomes, very little of the 32.5 min peak was produced with the 100,000 g supernatant fraction. Microsomal metabolism was increased 5-fold by pretreatment with Triton X-100. Very little activity was observed with rat microsomes in either the presence or absence of Triton X-100. This metabolite was also generated by incubating benzidine with glucuronic acid at 4 degrees C for 3 days. Thermospray MS identified this metabolite as benzidine N-glucuronide. At 37 degrees C, the t1/2 stability of purified N-glucuronide was 99, 25 and 3 min in dog urine adjusted to pH 7.3, 6.3 and 5.3 respectively. The N-glucuronide was quite stable at pH 9.3, in dog plasma, and in aprotic solvents for 4 h at 37 degrees C. Relative to benzidine, its N-glucuronide is weakly bound to plasma proteins but not more reactive with DNA. Thus, detoxification by liver provides a mechanism for accumulation of benzidine in acidic urine, uptake of benzidine into bladder epithelium, and activation of benzidine in bladder. The liver and N glucuronidation play a potentially important role in the species specificity of benzidine carcinogenesis. PMID- 1638693 TI - Liver DNA adducts in methyl-deficient rats administered a single dose of aflatoxin B1. AB - Using an 8 week Solt-Farber protocol with selection pressure (2 acetylaminofluorene/partial hepatectomy) applied during weeks 6 and 7, we have observed that a single oral administration of aflatoxin B1 (AFB1) to Fischer 344 rats on day 1 of the study, followed by a 3 week feeding regimen of either a methyl-deficient (CMD) or a basal (CMS) diet, results in a relative increase in hepatic preneoplastic lesions in CMD diet fed rats. It has previously been shown that a multiple dosing regimen with AFB1, started after 3 weeks of CMD diet, enhances tumor incidence. In the present study, the role of metabolic activation in the induction of preneoplastic lesions, and liver DNA adduct levels after the first dose of AFB1 in the tumorigenesis model have been investigated. AFB1-DNA adducts were determined at 2-168 h following a single non-necrogenic (100 micrograms/kg body wt) or necrogenic (600 micrograms/kg body wt) dose of AFB1 on day 1 or day 21 of a 3 week treatment with a complete basal or CMD diet. In all rats irrespective of dose, dietary treatment or time of AFB1 dosing, the patterns of adduct formation and repair did not change. In rats receiving AFB1 on day 1, total DNA adduct levels between the diet or dose groups were not significantly different, and quantitatively did not correlate with the observed increase in preneoplastic lesions, suggesting a contribution by additional factors in the initiation of these lesions. Administration of AFB1 on day 21, however, resulted in significantly reduced levels of total adducts at both dose levels in CMD diet fed rats compared to controls. Serum biochemistry data suggest that a prolonged exposure to CMD diet may cause pathological and/or biochemical alterations in hepatocytes with a resultant decrease in metabolic activation of AFB1, thus making it difficult to evaluate whether DNA damage is directly related to tumorigenesis. PMID- 1638694 TI - Determination of N7-methylguanine in DNA of white blood cells from cancer patients treated with dacarbazine. AB - An ELISA method was used to determine N7-methylguanine (N7-MeGua) adducts in DNA of white blood cells from cancer patients treated with the methylating antitumor drug dacarbazine by i.v. administration. From four patients who received dacarbazine only, at dosages of 250, 400 or 800 mg/m2, the blood samples were collected before and several days after administration, and from one patient also during the first few hours. N7-MeGua levels increased rapidly during the first hour after treatment, hardly changed during the following 7 h and decreased during the next days (half-life of approximately 72 h). The adduct levels appeared to be dose-dependent. Blood cells were also analyzed from three patients who received dacarbazine (225 mg/m2) in combination with other chemotherapeutic drugs during three successive days. One of these patients showed a larger initial level of N7-MeGua and a cumulative increase with the dacarbazine dose compared to the other two patients. For several patients adduct levels were monitored during two chemotherapy cycles, for which quite similar data were obtained. PMID- 1638695 TI - Chemoprevention of mammary carcinogenesis by hydroxylated derivatives of d limonene. AB - The monoterpene d-limonene has been shown to an effective, non-toxic chemopreventive agent in mammary and other rodent tumor models. The studies reported here investigated structure-activity relationships among limonene and three hydroxylated derivatives in the prevention of dimethylbenz[a]anthracene (DMBA)-induced mammary cancer. Rats were fed control or 1% limonene, carveol, uroterpenol or sobrerol diets from 2 weeks before to one week after carcinogen administration. Carveol, uroterpenol and sobrerol significantly prolonged tumor latency and decreased tumor yield. Sobrerol was the most potent of the monoterpenes tested, decreasing tumor yield to half that of the control, a level previously achieved with 5% limonene diets. Excretion of radioactivity from [3H]DMBA was doubled in rats fed 5% limonene and nearly tripled in rats fed 1% sobrerol. Sobrerol is thus 5-fold more potent than limonene in both enhancing carcinogen excretion and in preventing tumor formation. These data demonstrate that hydroxylation of monoterpenes affects chemopreventive potential, with 2 hydroxyl groups greater than 1 greater than 0. Sobrerol, carveol and uroterpenol are novel cancer chemopreventive agents with little or no toxicity. PMID- 1638696 TI - O6-alkylguanine-DNA alkyltransferase activity in epidermal tumor and normal epidermal cells of mice of various stocks and strains. AB - The level of the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (MGMT) was examined in benign and malignant skin tumors induced with different initiating and promoting agents and from both SENCAR and Sensitive SENCAR Inbred (SSIN) mice. The MGMT levels in the tumors were approximately one-half the level observed in normal surrounding epidermis and in keratinocytes from untreated controls. In addition, a carcinoma-producing cell line, VT 17DT, derived from papillomas in SENCAR mice had no detectable MGMT activity (Mer- phenotype), whereas in the non-tumor forming line, 3PC, MGMT activity was comparable to that in papillomas. The comparatively low level of MGMT in papillomas may contribute to their ease of conversion to squamous cell carcinomas by N-ethyl-N-nitrosourea or n-methyl-N'-nitro-N-nitrosoguanidine. MGMT activity was also determined in the epidermis of non-exposed mice of various stocks and strains. Epidermal MGMT activity was similar to levels in the corresponding livers and was, in general, parallel with stock/strain susceptibility to tumor formation. This is the first report that examined MGMT activity in skin tumors and normal keratinocytes in the mice of several stocks and strains. PMID- 1638697 TI - Increased 8-oxodeoxyguanosine levels in lung DNA of A/J mice and F344 rats treated with the tobacco-specific nitrosamine 4-(methylnitrosamine)-1-(3-pyridyl) 1-butanone. AB - Evidence for the involvement of free radicals in nitrosamine carcinogenesis comes mainly from increased lipid peroxidation as a result of nitrosamine treatment. More direct evidence for nitrosamine-induced oxidative DNA damage has been lacking. In this study we examined the levels of 8-oxodeoxyguanosine or 8 hydroxydeoxyguanosine (8-OH-dG) in tissue DNA of mice and rats treated with the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Multiple doses of NNK (0.25 or 0.50 mg/mouse, 3 times weekly for 3 weeks) administered by gavage resulted in a significant elevation of 8-OH-dG in lung DNA, from 2.1 to 3.8 adducts/10(5) dG for the lower dose or to 6.6 adducts/10(5) dG for the higher dose, 2 h after the last NNK administration. A single dose treatment of NNK by gavage (4 mg/mouse) also resulted in an increase of this lesion in the lung DNA, however, the increase was not statistically significant. In liver, however, the increase was only significant by multiple doses at the higher dose, from 2.3 to 3.4 adducts/10(5) dG. This lesion appeared to be repaired efficiently. At 4 and 24 h after NNK treatment, the 8-OH-dG levels declined to the basal levels in both liver and lung. A single dose of NNK (20 mg/rat) also caused a significant increase of 8-OH-dG from 3.0 to 5.1 adducts/10(5) dG in rat lung DNA. An increase of 8-OH-dG in liver DNA was also seen, however, it was not statistically significant. Unlike the liver and the lung, the 8-OH-dG levels in rat kidney, a non-target tissue, were inert to NNK treatment. These results provide for the first time direct evidence supporting the role of oxidative DNA damage in NNK lung tumorigenesis. PMID- 1638698 TI - Temporal changes in the mutant frequency and mutation spectra of the 61st codon of the H-ras oncogene following exposure of B6C3F1 mice to N-nitrosodiethylamine (DEN). AB - Hepatocellular tumors were induced in 15 day old male B6C3F1 mice following a single exposure to N-nitrosodiethylamine (DEN; 5 mg/kg, i.p.). Tumors were collected at 38 and 65 weeks to compare the frequencies and types of mutations in the 61st codon of the H-ras oncogene. The 61st codon was amplified using the polymerase chain reaction (PCR). Allele-specific oligonucleotide (ASO) probes were used to determine the frequency and types of mutations present in these tumors. Forty-nine nodular hepatic lesions were obtained from seven animals at the 38 week timepoint. Five of these samples (10%) had mutations at the 61st codon with one CAA-AAA, one CAA-CGA and three CAA-CTA. Thirty-six nodular hepatic lesions were obtained from six animals at the 65 week timepoint. Ten of these samples (28%) had mutations at the 61st codon with one CAA-AAA, five CAA-CGA and four CAA-CTA. These data indicate that DEN-induced mutations at the 61st codon of the mouse H-ras oncogene (i) are an infrequent event, (ii) have different frequencies at the 38 and 65 week timepoints and (iii) are different from the types of mutations seen in spontaneous lesions. PMID- 1638699 TI - Development and characterization of a sex-dependent metastatic preputial gland adenocarcinoma in human tumor-bearing immunosuppressed F344 rats. AB - Newborn F344 rats were treated with polyclonal rabbit anti-thymocyte serum, which caused partial immunosuppression for a limited period. These rats were injected s.c. with cells from human tumor cell lines (two melanomas and a B lymphoma). Within 46 days after the tumor regression a renal carcinosarcoma, resembling Wilms' tumor, developed in each animal, however in male rats an adenocarcinoma of the preputial gland arised. Chromosome analysis and transplantation experiments proved the rat origin of the new tumors. In the present study we describe the biological and morphological characteristics of the adenocarcinoma of the preputial gland (ACPG). Their invasive properties were demonstrated in the lung colony assay, after intra-arterial injection and in the spleen-liver model. ACPG showed unique metastatic phenotype: dependence on the sex of the host. PMID- 1638700 TI - Induction of DNA repair synthesis in human monocytes/B-lymphocytes compared with T-lymphocytes after exposure to N-acetoxy-N-acetylaminofluorene and dimethylsulfate in vitro. AB - We have explored the induction of DNA repair synthesis in monocyte/B- and T lymphocyte enriched cell fractions from 12 different human mononuclear blood cell populations. Unscheduled DNA synthesis was measured in monocyte/B- and T-cells after exposure to the DNA-damaging agents dimethylsulfate (DMS) and N-acetoxy-N acetylaminofluorene in vitro. Also, the binding of DMS to DNA was measured. An increased DNA repair synthesis was measured in monocyte/B-lymphocytes after induction of the two different types of DNA lesions, whereas no induction of unscheduled DNA synthesis was observed in T-lymphocytes. A significantly higher DMS-DNA binding was also observed in monocyte/B-lymphocytes when compared with T lymphocytes. Specific characterization of mononuclear blood cell populations used in biomonitoring of DNA adducts and repair is recommended. PMID- 1638701 TI - Phenol sensitization of DNA to subsequent oxidative damage in 8-hydroxyguanine assays. AB - The DNA base adduct, 8-hydroxyguanine (8-OHGua), has been reported to be a key biomarker relevant to carcinogenesis and cellular oxidative stress important in tumor promotion. Although investigators often report artificially high levels of 8-OHGua in DNA samples that have been exposed to phenol solutions and/or air during processing, few quantitative results are available. We show that routine phenol-based DNA purification procedures can increase 8-hydroxydeoxyguanosine (8 OHdG) levels 20-fold in samples that are exposed to air after the phenol is removed from the solutions. Surprisingly, air exposure alone accounts for a significant portion of this increase (4-fold) when compared to dG or DNA samples that have been solubilized in buffers purged with nitrogen. Most importantly, phenol treatments of DNA are shown to sensitize DNA to 8-OHdG formation by subsequent exposures to air. The sensitization of DNA occurs even though extensive dialysis is used between phenol treatment and enzymatic DNA digestion. Alternate procedures, including chloroform:isoamyl-alcohol extractions, also yield air-sensitive DNA samples. Other artifacts of organic extraction prior to air exposure include alterations in DNA base ratios after nuclease digestions. Overall, these results strongly suggest that studies of 8-OHdG in carcinogenesis should avoid dry conditions, such as lyophilization followed by exposure to air, and that all four of the bases should be monitored before 8-OHdG concentrations are normalized by undamaged deoxynucleoside concentrations. Failure to heed these precautions can lead to 2- to 20-fold overestimates of 8-OHdG in target tissues or in vitro models. PMID- 1638702 TI - The carcinogenic effect of methapyrilene combined with nitrosodiethylamine given to rats in low doses. AB - The carcinogenic effects of combinations of methapyrilene hydrochloride (MP), nitrosodiethylamine (NDEA), and phenobarbital (PB) or partial hepatectomy (PH) were examined following sequential treatment of rats. MP is a generally non genotoxic liver carcinogen of moderate potency, NDEA is a genotoxic liver carcinogen, PB is primarily a liver tumor promoter and PH induces cell proliferation. The dose of each carcinogen was chosen to be below that causing significant liver tumor incidence when given singly. There were 12 protocols involving groups of 28 female rats each. Short treatments with NDEA and MP were followed by 60 weeks of PB promotion or by partial hepatectomy. Each treatment was given separately or in double combination as controls. Several animals of each group were killed at intervals during the experiment for examination of toxic effects and the presence of altered hepatic foci. In only 3 of 12 groups was there a significant incidence of rats with liver neoplasms: the two groups given three treatments: NDEA, MP and PB (86% tumors) or NDEA, MP and PH (33%), and the group receiving NDEA and MP without promotion (46%). The results clearly indicated a co-carcinogenic effect between NDEA and MP. Continuous PB potentiated tumor development, while PH did not. There was no evidence of liver toxicity from any of the treatments, but clear cell foci observed in three groups at weeks 13 and 33 correlated with the later development of liver neoplasms. PMID- 1638703 TI - Differences in clinical expression of hypertrophic cardiomyopathy associated with two distinct mutations in the beta-myosin heavy chain gene. A 908Leu----Val mutation and a 403Arg----Gln mutation. AB - BACKGROUND: The disease gene for hypertrophic cardiomyopathy (HCM) has been identified as the beta-myosin heavy chain (beta-MHC) gene in some HCM families. We describe extensive clinical evaluations in two kindreds with two distinct point mutations in the beta-MHC gene. METHODS AND RESULTS: We used single-strand confirmation polymorphism (SSCP) gel analysis of polymerase chain reaction amplified products capturing each of the 40 beta-MHC gene exons to identify distinct missense mutations in two HCM kindreds. Clinical, ECG, and echocardiographic studies were performed in the two kindreds: kindred 2755 with amino acid 908Leu----Val mutation and kindred 2002 with amino acid 403Arg----Gln mutation. The morphological appearances of HCM were similar in these two kindreds. However, the two kindreds differed with respect to disease penetrance, age of onset of disease, and incidence of premature sudden death. Twelve of 31 adults (greater than or equal to 17 years) with the disease gene in kindred 2755 did not have left ventricular hypertrophy (LVH), and only five of these had ECG abnormalities. Thus, the disease penetrance in adults with this mutation was only 61%. None of 11 children aged less than 16 years had LVH. The 908 mutation was associated with a low incidence of cardiac events: Only two sudden deaths and one syncope occurred in 46 individuals with the mutant allele. In contrast, LVH was present in all 11 adults in kindred 2002 with the 403 mutation (100% disease penetrance). In addition, three of four affected children were symptomatic and had clinical evidence of HCM. The disease in this kindred was severe and resulted in six premature sudden deaths. Seven additional patients had syncope or presyncope. CONCLUSIONS: In some kindreds, the HCM disease gene is more prevalent than indicated by echocardiography and ECG. Some point mutations may be associated with a more malignant prognosis. Preclinical identification of children with mutations associated with a high incidence of sudden death and syncope provides the opportunity to evaluate efficacy of early therapeutic interventions. PMID- 1638704 TI - Transesophageal echocardiographic recognition of subaortic complications in aortic valve endocarditis. Clinical and surgical implications. AB - BACKGROUND: Secondary involvement of the mitral-aortic intervalvular fibrosa and the anterior mitral leaflet (subaortic structures) can occur in patients with aortic valve endocarditis. The secondary involvement of these structures occurs as a result of direct extension of the infection from the aortic valve or as a result of an infected aortic regurgitant jet striking the ventricular surfaces of the mitral-aortic intervalvular fibrosa and the anterior mitral leaflet. The abscess of mitral-aortic intervalvular fibrosa can expand to form an aneurysm. Subsequently, this mitral-aortic intervalvular fibrosa aneurysm can develop a perforation and communicate with the left atrium, resulting in the systolic regurgitation of blood from the left ventricular outflow tract into the left atrium. Secondary infection can also occur on the ventricular surface of the anterior mitral leaflet and result in the formation of an aneurysm or perforation of anterior mitral leaflet. METHODS AND RESULTS: This study examines the utility of transesophageal echocardiography in the detection of these subaortic complications in 55 consecutive patients with aortic valve endocarditis. A total of 24 patients (44%) had involvement of subaortic structures, including four with an abscess in the mitral-aortic intervalvular fibrosa, four with mitral-aortic intervalvular fibrosa aneurysm, seven with perforation of the mitral-aortic intervalvular fibrosa with communication into the left atrium, two with an aneurysm of the anterior mitral leaflet, and seven with perforation of the anterior mitral leaflet. The transesophageal echocardiographic findings were confirmed at surgery in 20 patients and at necropsy in two. By comparison, transthoracic echocardiography visualized these lesions in five of 24 patients (21%), including none of four with mitral-aortic intervalvular fibrosa abscesses, two of four with mitral-aortic intervalvular fibrosa aneurysms, one of seven with mitral-aortic intervalvular fibrosa perforations, one of two with anterior mitral leaflet aneurysms, and one of seven anterior mitral leaflet perforations. Eccentric mitral regurgitation-type systolic jets were noted in eight additional patients by transthoracic color flow imaging, and this finding suggested the possibility of these unusual subaortic complications. If these patients are included, then transthoracic echocardiography suggested the presence of these subaortic complications in 13 of 24 patients (54%). CONCLUSIONS: The results indicate that 1) involvement of the subaortic structures in patients with aortic valve endocarditis may be more common than previously recognized, 2) patients with aortic valve endocarditis and eccentric jets of mitral regurgitation on transthoracic echocardiography should undergo further evaluation by transesophageal echocardiography to exclude these unusual complications, 3) precise recognition of these complications is of value in the optimal medical and surgical management of these patients, and 4) these complications may be responsible for unexplained congestive heart failure and hemodynamic deterioration in some patients with aortic valve endocarditis. PMID- 1638705 TI - Efficacy of automatic multimodal device therapy for ventricular tachyarrhythmias as delivered by a new implantable pacing cardioverter-defibrillator. Results of a European multicenter study of 102 implants. AB - BACKGROUND: Third-generation implantable cardioverter-defibrillators are devices designed to treat ventricular tachycardia (VT) and ventricular fibrillation (VF) by means of overdrive pacing, cardioversion, or defibrillation. So far, the efficacy of tiered therapy has been documented only in small series. Therefore, a European multicenter clinical evaluation study of a new tachyarrhythmia control device, the Medtronic PCD pacer-cardioverter-defibrillator with epicardial patch lead configuration, was undertaken. METHODS AND RESULTS: We report on 102 patients (mean age, 55 +/- 13 years) from 11 European centers. PCD devices implanted between May 1989 and February 1991 were included. The patients suffered from hemodynamically significant ventricular tachyarrhythmias not suppressed by antiarrhythmic drug therapy and unrelated to acute myocardial infarction; one patient had nonsustained VT and severely depressed left ventricular function. Seventy patients had coronary artery disease with old myocardial infarctions, 23 had cardiomyopathies of various etiologies, and nine patients had no detectable heart disease. Mean ejection fraction was 36 +/- 14% (range, 10-76%). Mean intraoperative defibrillation threshold (51 patients) was 10.6 +/- 5.1 J (range, 2-18 J). The documented follow-up ranged from 1 to 21 months (mean, 9.4 +/- 5.8 months), or 79.9 cumulative patient-years. Perioperative mortality was 3.9%. The actuarial survival rate at 12 months was 91%. One sudden arrhythmic death occurred. Sixty patients (58%) received device therapy. Seventeen patients had therapies only for "VF" episodes, 16 patients only for VT, and 28 patients for VT and "VF" episodes. Based on device memory data, 1,235 spontaneous VT episodes were detected and treated in 43 patients. Twelve hundred four of these VT episodes received painless initial antitachycardia pacing therapy, restoring sinus rhythm in 91%. The 108 ongoing episodes received 209 multiple therapeutic attempts. Eighty-five additional overdrive pacing therapies restored sinus rhythm in 30%. Initial ineffective antitachycardia pacing therapies received 51 cardioversion pulses. The success rate was 61%. Seventy-three additional cardioversion pulses were delivered to backup ineffective pacing therapy as well as ineffective secondary cardioversion pulses. Their success rate was only 40%. Two hundred eighty-six spontaneous episodes were detected in 44 patients as "VF." Overall defibrillation efficacy was 97.6%. CONCLUSIONS: The implanted device nearly eliminates sudden arrhythmic death in patients with documented, potentially fatal ventricular tachyarrhythmias. Automatic tiered therapy is highly effective to restore sinus rhythm, provided that an integrated two-zone tachycardia detection algorithm is used, assigning lower tachycardia rates to overdrive pacing and/or cardioversion and higher tachycardia rates to defibrillation. In general, spontaneous VTs can be terminated by automatic overdrive pacing, and painful or disturbing countershock therapies are not required to terminate the majority of spontaneous VT episodes. PMID- 1638706 TI - Evidence for transient linking of atrial excitation during atrial fibrillation in humans. AB - BACKGROUND: Atrial fibrillation is usually thought of as a "random" pattern of circulating wavelets. However, local atrial activation should be influenced by the constant anatomy and receding tail of refractoriness from the previous activation. The general tendency for wave fronts to follow paths of previous excitation has been termed "linking." We examined intra-atrial electrograms recorded during atrial fibrillation for evidence of linking. METHODS AND RESULTS: Two minutes of atrial fibrillation were recorded in 15 patients with an orthogonal catheter. We have previously demonstrated that this catheter can be used to detect changes in the direction of local atrial activation. A mean vector was calculated for each electrogram. The similarity of the direction of the vectors from two consecutive electrograms can be quantified on a scale of 1 to -1 by calculating the cosine (cos) of the smallest angle (theta) between them. Two vectors pointing in the same or opposite directions then have cos(theta) = 1 or 1, respectively. For the entire group of patients, mean cos(theta) was significantly greater than 0 (mean, 0.36; p less than 0.001). In nine of 15 patients, there were groups of six or more consecutive beats (total, 44 groups; range, six to 14 beats per group) in which the direction of activation of each beat was within 30 degrees of the previous beat. The likelihood of one group of six or 14 consecutive similar beats occurring by chance in any one patient in 1 minute is less than 0.05 and less than 0.0000001, respectively. There was a significant correlation (r = 0.90) between the amount of linking during the first and second minutes of atrial fibrillation in each patient. CONCLUSIONS: Transient similarities in the direction of wavelet propagation in the majority of patients with atrial fibrillation is consistent with the presence of transient linking. To our knowledge, this is the first direct evidence that atrial activation during atrial fibrillation in humans is not entirely random. PMID- 1638707 TI - Electrocardiographic body surface mapping in patients with ventricular tachycardia. Assessment of utility in the identification of effective pharmacological therapy. AB - BACKGROUND: Body surface maps of net QRST deflection areas (isointegrals) reflect regional ventricular repolarization properties. Vulnerability to ventricular tachyarrhythmias is associated with maps that feature multiple islands (extrema) of positive and negative values; such maps reflect regional disparity of ventricular recovery properties. The value of body surface mapping in prediction of the efficacy of antiarrhythmic therapy for ventricular tachyarrhythmias has not been determined. METHODS AND RESULTS: Isointegral ECG body surface mapping was performed in 51 patients with inducible ventricular tachycardia having programmed stimulation studies at baseline and after oral quinidine therapy. The degree of nondipolarity of QRST isointegral distribution was expressed by the number of extrema and by the percentage contribution of nondipolar eigenvectors after Karhunen-Loeve transformation. QRST isointegral nondipolarity was greater in ventricular tachycardia patients than in 51 age- and sex-matched normal subjects expressed as mean number of extrema (4.1 +/- 2.8 versus 2.0 +/- 0.2, respectively), mean eigenvector-determined nondipolar content percentages (12.4 +/- 10.1% versus 4.5 +/- 4.9%), prevalence of abnormal numbers of extrema (63% versus 4%), or prevalence of abnormal nondipolar content percentages (33% versus 4%) (each p less than 0.01). Quinidine prevented ventricular tachycardia induction in 14 patients. Patients for whom quinidine was or was not effective had similar nondipolarity indexes at baseline. However, maps on quinidine differed as a function of antiarrhythmic efficacy. Although effective therapy produced no significant mean changes in nondipolarity, ineffective therapy increased the number of extrema compared with baseline (5.4 +/- 3.4 versus 3.8 +/ 2.5, respectively) (p = 0.002). Individually, 43% of patients on effective therapy had drug-induced decreases in numbers of extrema compared with 14% of those on ineffective therapy (p = 0.02). Furthermore, 29% of patients on effective therapy showed drug-induced increases in numbers of extrema compared with 62% of those on ineffective therapy (p = 0.03). CONCLUSIONS: QRST isointegral body surface mapping shows promise as a noninvasive measure of drug efficacy in patients with ventricular tachycardia. PMID- 1638708 TI - Association between heart rate and atherogenic blood lipid fractions in a population. The Tromso Study. AB - BACKGROUND: Prospective epidemiological studies indicate that elevated heart rate may carry increased risk for coronary heart disease. Little is known about the relation between heart rate and serum lipid and lipoprotein concentrations in the general population. METHODS AND RESULTS: We assessed anthropometric and life style determinants of heart rate and examined the association between heart rate and serum lipid and lipoprotein concentrations in a cross-sectional study of 9,719 men and 9,433 women 12-59 years old. Stratified and multivariate analyses were used to detect possible modification of effect and to control for confounding variables. Heart rate was positively associated with male sex and smoking, decreased with body height and physical activity, and showed a U-shaped relation to body mass index. In both sexes, there was a significant progressive increase in age-adjusted levels of total cholesterol, non-high density lipoprotein (HDL) cholesterol, and triglycerides and a decrease in HDL cholesterol with heart rate. Men with heart rate greater than 89 beats per minute had 14.5% higher non-HDL cholesterol and 36.3% higher triglyceride levels than men with heart rate less than 60 beats per minute. The corresponding differences in women were 12.5% and 22.2%. The associations remained significant when anthropometric and life-style factors were controlled for. The slopes relating total and non-HDL cholesterol level to heart rate were steeper with advancing age. CONCLUSIONS: Increases in heart rate correlate with higher levels of atherogenic serum lipid fractions in the general population. Alterations in aortic impedance and/or autonomic influences may underlie these associations. PMID- 1638709 TI - Effects of traditional coronary risk factors on rates of incident coronary events in a low-risk population. The Adventist Health Study. AB - BACKGROUND: California Seventh-Day Adventists have lower mortality rates from coronary heart disease (CHD) than other Californians. Associations between traditional risk factor and CHD events have not been reported previously for Adventists. METHODS AND RESULTS: A cohort study allowed 6 years of follow-up of 27,658 male and female California Seventh-Day Adventists. Data collected included age, sex, physician-diagnosed hypertension and diabetes mellitus, body height, weight, previous and current cigarette smoking habits, and current exercise habits. Incident cases of definite myocardial infarction (MI) and definite fatal CHD were diagnosed according to recognized criteria. Both stratified and proportional hazards analyses demonstrated that in this low-risk population, the above traditional coronary risk factors exhibit their usual associations with risk of CHD events. It was noted that exercise had a strong negative association with fatal CHD events (relative risks [RR], 1.0, 0.66, and 0.50 with increasing exercise) but no association with risk of MI (either nonfatal or all cases). Conversely, obesity was much more clearly associated with MI (RR, 1.0, 1.18, and 1.83 with increasing tertiles of obesity) than with fatal events. The importance of the risk factors was similar in both sexes, except that the effect of cigarette smoking seemed more pronounced in women. CONCLUSIONS: The epidemiology of coronary heart disease in this low-risk California population appears to be at least qualitatively similar to that seen in other groups. There was evidence that the effects of exercise and obesity may differ depending on whether fatal CHD and MI (either all MI or nonfatal alone) is the end point. PMID- 1638710 TI - Thrombus regression in deep venous thrombosis. Quantification of spontaneous thrombolysis with duplex scanning. AB - BACKGROUND: Thrombus regression in heparin-treated, acute deep venous thrombosis of the lower extremity is poorly documented in the literature; different rates of thrombus resolution and recanalization are reported. METHODS AND RESULTS: In a prospective follow-up study, duplex scanning was used to evaluate the thrombus regression in patients with documented acute femoropopliteal thrombosis. Eighty vein segments in 20 legs of 18 patients were subjected to repeat duplex scans at 1, 3, 6, 12, and 26 weeks after diagnosis; 49 segments showed thrombus at diagnosis. The popliteal vein showed the highest thrombus load at diagnosis, followed in descending order by the superficial femoral, profunda femoris, and common femoral vein segments (p less than 0.001). Thrombus regression was significant (p less than 0.001) in all segments and proceeded at an exponential rate that was equal in the different vein segments of the upper leg. Both thrombus resolution and recanalization appeared to be a function of the initial thrombus load and could not be related to individual vein segments. Recanalization was seen in 23 of 31 initially occluded segments and occurred within the first 6 weeks after diagnosis in 20 of 23 segments. Extension of thrombus despite anticoagulant therapy was observed in 15 vein segments and was not related to the initial thrombosis score (p = 0.1) or individual vein segments (p = 0.23). Thrombus extension in seven patients with prethrombotic conditions was not different (p = 0.9) from the other patients. CONCLUSIONS: Duplex scanning is an important noninvasive tool to quantify thrombus regression in acute deep venous thrombosis in detail without unnecessary discomfort to the patient. PMID- 1638711 TI - Structural remodeling of cardiac myocytes in patients with ischemic cardiomyopathy. AB - BACKGROUND: Chronic ischemic heart disease may lead to ventricular dilation and congestive heart failure (ischemic cardiomyopathy [ICM]). The changes in cardiac myocyte shape associated with this dilation, however, are not known. METHODS AND RESULTS: Left ventricular myocyte dimensions were assessed in cells isolated from explanted human hearts obtained from patients with ICM (n = 6) who were undergoing heart transplantation. Cells were also examined from three nonfailing donor hearts with normal coronary arteries (NCA). Compared with cells from patients with NCA, myocyte length was 40% longer in hearts from patients with ICM (197 +/- 8 versus 141 +/- 9 microns, p less than 0.01), cell width was not significantly different, and cell length/width ratio was 49% greater (11.2 +/- 0.9 versus 7.5 +/- 0.6, p less than 0.01). Sarcomere length was the same in myocytes from both groups. The extent of myocyte lengthening is comparable to the increase in end-diastolic diameter commonly reported in patients with ICM. CONCLUSIONS: These data suggest that increased myocyte length (an intracellular event), instead of myocyte slippage (an extracellular event), is largely responsible for the chamber dilation in ICM. Furthermore, maladaptive remodeling of myocyte shape (e.g., increased myocyte length/width ratio) may contribute to the elevated wall stress (e.g., increased chamber radius/wall thickness) in ICM. PMID- 1638712 TI - Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dysfunction in patients with heart failure. SOLVD Investigators. AB - BACKGROUND: In patients with heart failure, activation of the renin-angiotensin system is common and has been postulated to provide a stimulus for further left ventricular (LV) structural and functional derangement. We tested the hypothesis that chronic administration of the angiotensin converting enzyme (ACE) inhibitor enalapril prevents or reverses LV dilatation and systolic dysfunction among patients with depressed ejection fraction (EF) and symptomatic heart failure. METHODS AND RESULTS: We examined subsets of patients enrolled in the Treatment Trial of Studies of Left Ventricular Dysfunction (SOLVD). Fifty-six patients with mild to moderate heart failure underwent serial radionuclide ventriculograms, and 16 underwent serial left heart catheterizations, before and after randomization to enalapril (2.5-20 mg/day) or placebo. At 1 year, there were significant treatment differences in LV end-diastolic volume (EDV; p less than 0.01), end systolic volume (ESV; p less than 0.005), and EF (p less than 0.05). These effects resulted from increases in EDV (mean +/- SD, 136 +/- 27 to 151 +/- 38 ml/m2) and ESV (103 +/- 24 to 116 +/- 24 ml/m2) in the placebo group and decreases in EDV (140 +/- 44 to 127 +/- 37 ml/m2) and ESV (106 +/- 42 to 93 +/- 37 ml/m2) in the enalapril group. Mean LVEF increased in enalapril patients from 0.25 +/- 0.07 to 0.29 +/- 0.08 (p less than 0.01). There was a significant treatment difference in LV end-diastolic pressure at 1 year (p less than 0.05), with changes paralleling those of EDV. The time constant of LV relaxation changed only in the placebo group (p less than 0.01 versus enalapril), increasing from 59.2 +/- 8.0 to 67.8 +/- 7.2 msec. Serial radionuclide studies over a period of 33 months showed increases in LV volumes only in the placebo group. Two weeks after withdrawal of enalapril, EDV and ESV increased to baseline levels but not to the higher levels observed with placebo. CONCLUSIONS: In patients with heart failure and reduced LVEF, chronic ACE inhibition with enalapril prevents progressive LV dilatation and systolic dysfunction (increased ESV). These effects probably result from a combination of altered remodeling and sustained reduction in preload and afterload. PMID- 1638713 TI - Furosemide-induced natriuresis is augmented by ultra-low-dose captopril but not by standard doses of captopril in chronic heart failure. AB - BACKGROUND: Ten chronic heart failure patients were studied on three occasions in randomized double-blind fashion to compare the acute hemodynamic, neurohormonal, and renal sodium-handling responses to 1 mg captopril versus 25 mg captopril, both in the absence of loop diuretic therapy and during furosemide-stimulated natriuresis. METHODS AND RESULTS: Compared with placebo, 1 mg captopril caused nonsignificant decreases in mean arterial pressure and circulating angiotensin II level and had no effect on glomerular filtration rate as determined by 51Cr-EDTA elimination. Captopril (25 mg) produced marked suppression of serum angiotensin II with or without oral furosemide (both p less than 0.002), a marked decrease in mean arterial pressure (p less than 0.001) that was accentuated by furosemide (p less than 0.00001), and a decrease in glomerular filtration rate (p = 0.0007). No difference from placebo in renal sodium excretion was noted with either 1 or 25 mg captopril in the absence of furosemide. In contrast, while 25 mg captopril caused slight attenuation of the natriuretic response to furosemide, 1 mg captopril significantly enhanced furosemide-induced natriuresis (p less than 0.05). No correlation was found in our patients between the natriuretic effect of furosemide and either absolute mean arterial pressure or change in mean arterial pressure during the furosemide phase of each study session. This suggests that blood pressure is not the important factor mediating the divergent renal responses to furosemide of the two captopril dosage regimens. CONCLUSIONS: We propose that in the face of furosemide-induced postglomerular vasodilatation in chronic heart failure, captopril at a starting dose of 1 mg (but not 25 mg) preserves enough circulating angiotensin II to maintain efferent arteriolar tone and thus glomerular filtration, while offsetting the antinatriuretic renal tubular effects of angiotensin II. PMID- 1638714 TI - Effect of completeness of revascularization on long-term outcome of patients with three-vessel disease undergoing coronary artery bypass surgery. A report from the Coronary Artery Surgery Study (CASS) Registry. AB - BACKGROUND: Complete revascularization after coronary artery bypass surgery is a logical goal and improves symptomatic outcome and survival. However, the impact of complete revascularization in patients with three-vessel coronary disease with varying severities of angina and left ventricular dysfunction has not been clearly defined. METHODS AND RESULTS: The study was performed as a retrospective analysis of 3,372 nonrandomized surgical patients from the Coronary Artery Surgery Study (CASS) Registry who had three-vessel coronary disease. Group 1 (894 patients) had class I or II angina (Canadian Cardiovascular Society criteria) and group 2 (2,478 patients) had class III or IV angina. In group 1, adjusted cumulative 4-year survivals according to the number of vessels bypassed were 85% (one vessel), 94% (two vessels), 96% (three vessels), and 96% (more than three vessels) (log rank, p = 0.022). Adjusted event-free survival (death, myocardial infarction, definite angina, or reoperation) was not influenced by the number of vessels bypassed, nor was the anginal status among patients remaining alive after 5 years. In group 2, adjusted cumulative 5-year survivals were 78% (one vessel), 85% (two vessels), 90% (three vessels), and 87% (more than three vessels) (log rank, p = 0.074). Adjusted event-free survivals after 6 years were 23% (one vessel), 23% (two vessels), 29% (three vessels), and 31% (more than three vessels) (p = 0.025); at 5 years, those with more complete revascularization were more likely to be asymptomatic or free of severe angina. Among group 2 patients with ejection fractions less than 0.35, 6-year survival was 69% for those with grafts to three or more vessels versus 45% for those with grafts to two vessels (p = 0.04). Placing grafts to three or more vessels was independently associated with improved survival and event-free survival in group 2 but not group 1 patients. The case-fatality rates among 529 patients experiencing a myocardial infarction during follow-up was significantly higher for patients with less complete revascularization. CONCLUSIONS: Complete revascularization (grafts to three or more vessels) in patients with three-vessel coronary disease appears to most benefit those with severe angina and left ventricular dysfunction. PMID- 1638715 TI - Coronary angioplasty in cardiac transplant patients. Results of a multicenter study. AB - BACKGROUND: Accelerated allograft atherosclerosis is the main cause of death of cardiac transplant recipients after the first year after transplantation. Because no medical therapy is known to prevent or retard graft atherosclerosis and transplantation is associated with a shortened allograft survival, alternative, palliative therapy with percutaneous transluminal coronary angioplasty (PTCA) has been attempted. Because no single medical center has performed angioplasty in a large number of cardiac transplant recipients, representatives of 11 medical centers retrospectively analyzed their complete experience of coronary angioplasty in cardiac transplant patients to determine the safety, efficacy, limitations, and long-term outcome of angioplasty in allograft coronary vascular disease. METHODS AND RESULTS: Thirty-five patients underwent 51 angioplasty procedures for 95 lesions 46 +/- 5 months (mean +/- SEM) after transplantation. The primary indications for angioplasty included angiographic coronary disease in 22 cases (43%) and noninvasive evidence of ischemia in 18 procedures (35%). Angiographic success, defined as less than or equal to 50% post-PTCA stenosis, occurred in 88 of 95 lesions (93%). Mean pre-PTCA stenosis was 83 +/- 1.1%; mean post-PTCA stenosis was 29 +/- 2.1% (p less than 0.0001). Periprocedural complications included myocardial infarction and late in-hospital death in one patient and three groin hematomas. Twenty-three of the 35 patients (66%) had no major adverse outcome such as death, retransplantation, or myocardial infarction at 13 +/- 3 months after angioplasty. Four patients died less than 6 months after angioplasty, and four died more than 6 months after angioplasty (range, 6-23 months). Two patients had retransplantation 2 months after PTCA, and one patients had retransplantation 18 months after angioplasty. CONCLUSIONS: Coronary angioplasty may be applied in selected cardiac transplant recipients with comparable success and complication rates to routine angioplasty. Whether angioplasty prolongs allografts survival remains to be determined by a prospective, controlled trial. PMID- 1638716 TI - Ventricular fibrillation in hypertrophic cardiomyopathy is associated with increased fractionation of paced right ventricular electrograms. AB - BACKGROUND: Intraventricular conduction in hypertrophic cardiomyopathy (HCM) has been characterized to test the hypothesis that myofibrillar disarray will cause dispersion of activation throughout the ventricular myocardium. METHODS AND RESULTS: Of 37 patients with HCM, four had spontaneous ventricular fibrillation (VF), five had nonsustained ventricular tachycardia (VT), 13 had no risk factors, and 15 had a family history of sudden death. These patients and four controls were studied by pacing one site in the right ventricle and recording electrograms from three other right ventricular sites. These electrograms were high-pass filtered to emphasize small deflections due to activation of small bundles of myocytes close to the electrode. Intraventricular conduction curves were obtained with S1S2 coupling intervals decreasing in 1-msec steps from 479 msec to ventricular effective refractory period (VERP). These curves were repeated by pacing each RV site in turn and were characterized by two parameters: the point at which latency increased by 0.75 msec/20 msec reduction of the S1S2 coupling interval and an increase in electrogram duration between an S1S2 of 350 msec and VERP. Patients with VF, VT, and family history of sudden death had a mean increase in electrogram duration of 12.8 (2.9-32.3) msec versus 4.6 (-4.2 to 14.0) msec in low-risk patients and controls. Electrogram latency increased at an S1S2 of 363 msec in the VF group (342-386), 269 msec in the controls (266-279), and 326 msec in the non-VF group (260-399). Discriminant analysis separated VF patients from the remainder (p less than 0.0001) and VF, VT, and family history of sudden death patients from the low-risk and control groups (p less than 10( 6)). CONCLUSIONS: Patients with HCM who are at risk of sudden death have increased dispersion and inhomogeneity of intraventricular conduction, and this may create the conditions for reentry and arrhythmogenesis. PMID- 1638717 TI - Effects of aging, sex, and physical training on cardiovascular responses to exercise. AB - BACKGROUND: The relative contributions of decreases in maximal heart rate, stroke volume, and oxygen extraction and of changes in body weight and composition to the age-related decline in maximal oxygen uptake (VO2max) are unclear and may be influenced by sex and level of physical activity. METHODS AND RESULTS: To investigate mechanisms by which aging, sex, and physical activity influence VO2max, we quantified VO2, cardiac output, and heart rate during submaximal and maximal treadmill exercise and assessed weight and fat-free mass in healthy younger and older sedentary and endurance exercise-trained men and women. For results expressed in milliliters per kilogram per minute, a three-to-four-decade greater age was associated with a 40-41% lower VO2max in sedentary subjects and a 25-32% lower VO2max in trained individuals (p less than 0.001). A smaller stroke volume accounted for nearly 50% of these age-related differences, and the remainder was explained by a lower maximal heart rate and reduced oxygen extraction (all p less than 0.001). Age-related effects on maximal heart rate and oxygen extraction were attenuated in trained subjects (p less than 0.05). After normalization of VO2max and maximal cardiac output to fat-free mass, age- and training-related differences were reduced by 24-47% but remained significant (p less than 0.05). For trained but not sedentary subjects, maximal cardiac output and stroke volume normalized to fat-free mass were greater in men than in women (p less than 0.05). CONCLUSIONS: A lower stroke volume, heart rate, and arteriovenous oxygen difference at maximal exercise all contribute to the age related decline in VO2max. Effects of age and training on VO2max, maximal cardiac output, and stroke volume cannot be fully explained by differences in body composition. In sedentary subjects, however, the sex difference in maximal cardiac output and stroke volume can be accounted for by the greater percentage of body fat in women than in men. PMID- 1638718 TI - Differences in cardiovascular responses to isoproterenol in relation to age and exercise training in healthy men. AB - BACKGROUND: Cardiac aging is characterized by a reduced heart rate response to beta-agonist stimulation with isoproterenol, but whether the ejection fraction and other cardiovascular responses are reduced in humans is largely unknown. In addition, whether reduced beta-agonist responses can be improved with exercise training has not been determined in humans. METHODS AND RESULTS: Cardiovascular responses to graded isoproterenol infusions (3.5, 7, 14, and 35 ng/kg/min for 14 minutes each) were assessed in 15 older (age, 60-82 years) and 17 young (age, 24 32 years) rigorously screened healthy men. Thirteen older and 11 young subjects completed 6 months of endurance training and were retested. At baseline, the older group had reduced responses to isoproterenol for heart rate (+65% older versus +92% young, p less than 0.001), systolic blood pressure (+9% versus +24%, p less than 0.001), diastolic blood pressure (-12% versus -24%, p less than 0.05), ejection fraction (+12 versus +20 ejection fraction units, p less than 0.001), and cardiac output (+70% versus +100%, p less than 0.001). The mean plasma isoproterenol concentrations achieved during the infusions were marginally higher (p = 0.07) in the older group (128 +/- 58, 227 +/- 64, 354 +/- 114, and 700 +/- 125 pg/ml) than in the young (79 +/- 20, 178 +/- 49, 273 +/- 79, and 571 +/- 139 pg/ml). Intensive training increased maximal oxygen consumption by 21% in the older group (28.9 +/- 4.6 to 35.1 +/- 3.8 ml/kg/min, p less than 0.001) and by 17% in the young (44.5 +/- 5.1 to 52.1 +/- 6.3 ml/kg/min, p less than 0.001), but training did not augment any of the cardiovascular responses to isoproterenol in either group. The mean plasma isoproterenol concentrations at the four infusion doses were unchanged after training in both groups. CONCLUSIONS: We conclude that there is an age-associated decline in heart rate, blood pressure, ejection fraction, and cardiac output responses to beta-adrenergic stimulation with isoproterenol in healthy men. Altered beta-adrenergic responses probably contribute to the reduced cardiac responses to maximal exercise that also occur with aging. Furthermore, intensive exercise training does not increase cardiac responses to beta-adrenergic stimulation with isoproterenol in either young or older men. The reduced beta-adrenergic response appears to be a primary age associated change that is not caused by disease or inactivity. PMID- 1638719 TI - Effective arterial elastance as index of arterial vascular load in humans. AB - BACKGROUND: This study tested whether the simple ratio of ventricular end systolic pressure to stroke volume, known as the effective arterial elastance (Ea), provides a valid measure of arterial load in humans with normal and aged hypertensive vasculatures. METHODS AND RESULTS: Ventricular pressure-volume and invasive aortic pressure and flow were simultaneously determined in 10 subjects (four young normotensive and six older hypertensive). Measurements were obtained at rest, during mechanically reduced preload, and after pharmacological interventions. Two measures of arterial load were compared: One was derived from aortic input impedance and arterial compliance data using an algebraic expression based on a three-element Windkessel model of the arterial system [Ea(Z)], and the other was more simply measured as the ratio of ventricular end-systolic pressure to stroke volume [Ea(PV)]. Although derived from completely different data sources and despite the simplifying assumptions of Ea(PV), both Ea(Z) and Ea(PV) were virtually identical over a broad range of altered conditions: Ea(PV) = 0.97.Ea(Z) + 0.17; n = 33, r2 = 0.98, SEE = 0.09, p less than 0.0001. Whereas Ea(PV) also correlated with mean arterial resistance, it exceeded resistance by as much as 25% in older hypertensive subjects (because of reduced compliance and wave reflections), which better indexed the arterial load effects on the ventricle. Simple methods to estimate Ea (PV) from routine arterial pressures were tested and validated. CONCLUSIONS: Ea(PV) provides a convenient, useful method to assess arterial load and its impact on the human ventricle. These results highlight effects of increased pulsatile load caused by aging or hypertension on the pressure-volume loop and indicate that this load and its effects on cardiac performance are often underestimated by mean arterial resistance but are better accounted for by Ea. PMID- 1638720 TI - A recombinant, chimeric enzyme with a novel mechanism of action leading to greater potency and selectivity than tissue-type plasminogen activator. AB - BACKGROUND: Early intervention with thrombolytic agents has been shown unequivocally to reduce mortality after acute myocardial infarction. Presently used agents have disadvantages such as short half-life, immunogenicity, hypotension, and bleeding complications. Therefore, there is a need to develop improved thrombolytic drugs with novel mechanisms of action leading to improved properties. METHODS AND RESULTS: Hybrid plasminogen/tissue-type plasminogen activator (t-PA) complementary DNA was constructed and expressed in Chinese hamster ovary cells. The chimeric protein, comprising the fibrin-binding domains of plasminogen covalently linked to the catalytic domain of t-PA, was purified and evaluated in vitro and in vivo. The hybrid was inhibited rapidly in human and animal plasmas. The mediator of this rapid inhibition was shown to be alpha 2 antiplasmin. The active center of the hybrid could be protected by reversible active center acylation with a novel inverse acylating agent, 4'-amidinophenyl-4 chloroanthranilic acid (AP-CLAN). An acylated (CLAN-) hybrid was cleared from the bloodstream of guinea pigs at 0.35 +/- 0.02 ml/min.kg-1 compared with a clearance rate of 36 +/- 4 ml/min.kg-1 for t-PA. The CLAN-plasminogen/t-PA hybrid was evaluated in a quantitative, "humanized" guinea pig pulmonary embolism model and shown to be approximately threefold more potent when given by bolus than an infusion of t-PA. Furthermore, the acylated hybrid was more fibrin selective than t-PA as determined by the relation between clot lysis and fibrinogen degradation. CONCLUSIONS: An acylated, recombinant plasminogen/t-PA hybrid has sufficiently slow clearance to be administered by bolus and is more potent and fibrin selective than t-PA in vivo. PMID- 1638721 TI - A mathematical model for the quantification of mitral regurgitation. Experimental validation in the canine model using contrast echocardiography. AB - BACKGROUND: Because the clearance of contrast from the left atrium (LA) relative to the left ventricle (LV) depends on the degree of mitral regurgitation (MR), we hypothesized that a mathematical model can be developed that would provide a quantitative estimation of MR from the washout of contrast from these chambers. METHODS AND RESULTS: After mathematically developing the model, we performed experiments in two groups of dogs with the use of contrast echocardiography. Group 1 consisted of nine dogs in which different degrees of MR were produced by creating ischemic LV dysfunction. Contrast was injected into the LV, and MR was graded visually on a scale of from 0 to 4+. Videointensity plots generated from the LA and LV were provided to the model. There was excellent correlation between visual assessment of MR and model-derived regurgitant fraction in the 33 stages: y = 0.16x + 0.002 (r = 0.97, p less than 0.001, SEE = 0.06). To obtain a more quantitative validation, we placed electromagnetic flow probes on the aorta and just cephalad to the mitral annulus in six dogs (group 2) during cardiopulmonary bypass. Different degrees of MR were produced by chordal traction and/or myocardial ischemia. Regurgitant fraction was calculated at each stage from the flow probe and videointensity data. There was excellent correlation between flow probe and model-derived regurgitant fraction (y = 0.90x + 0.03; r = 0.96, p less than 0.001, SEE = 0.06), and close interobserver and intraobserver correlations were noted using flow probe and contrast echocardiographic data. CONCLUSIONS: A mathematical model that uses the clearance of contrast from the LA relative to the LV can be used to accurately measure the severity of MR. These findings may have important practical implications for the quantification of MR. PMID- 1638722 TI - Influence of the force-frequency relation on left ventricular function during exercise in conscious dogs. AB - BACKGROUND: The magnitude of the force-frequency effect on myocardial contractility in the conscious animal has been studied at rest, but it has not been assessed during exercise. METHODS AND RESULTS: The influence of heart rate (HR) changes were evaluated during treadmill exercise in eight preinstrumented, conscious dogs in which high-fidelity left ventricular (LV) pressure, LV volume (by sonomicrometry), and aortic pressure were measured. Under resting conditions, end-systolic pressure-volume relations were obtained using inferior vena caval occlusion. Dogs were run on a treadmill, and the intrinsic exercise HR was reduced by infusion of a specific bradycardic drug (UL-FS 49 0.5 mg/kg) during continuing exercise while HR was maintained at 240 beats per minute by atrial pacing. At 6 minutes of running at a fixed, paced HR when a stable drug effect had been achieved, no effects of UL-FS 49 on measures of LV contractility were detected compared with exercise before drug administration. HR was then reduced stepwise from 240 to 210, 180, or 150 beats per minute in a random manner, returning to 240 beats per minute between steps. Progressive reductions in measures of myocardial contractility occurred as the HR was slowed, and reduction of rate from 240 to 150 beats per minute reduced the LV maximum positive dP/dt by 31% and (dP/dt)DP40 by 21% despite increases in LV end-diastolic pressure. The entire end-systolic pressure-volume could not be determined during exercise, but beat-averaged end-systolic pressure-volume points during exercise were progressively shifted to the right and downward by slowing the exercise HR. Thus, a pronounced negative inotropic influence of slowing the heart was observed during exercise, and the rate of ventricular relaxation (tau) was also significantly prolonged. CONCLUSIONS: These findings indicate that force frequency effects on the inotropic state of the intact LV are markedly enhanced by exercise. PMID- 1638723 TI - Severe right ventricular pressure loading in fetal sheep augments global myocardial blood flow to submaximal levels. AB - BACKGROUND: It has previously been shown that the fetal right ventricle (RV) is sensitive to changes in arterial pressure and that its stroke volume is significantly reduced with acute increases in pulmonary arterial pressure. However, the myocardial blood flow (MBF) response to increases in pulmonary arterial pressure have not been investigated in the fetus. METHODS AND RESULTS: To assess whether the RV afterload sensitivity to arterial pressure is associated with limitation in MBF, seven fetal lambs were instrumented at 130 days of gestation with a pulmonary arterial occluder and intravascular catheters. RV stroke volume was measured by an electromagnetic flow probe and MBF by 15-microns labeled microspheres. MBF was determined at baseline and during incremental increases in pulmonary arterial pressure. Maximal MBF was determined in seven additional fetuses during adenosine infusion. The highest tolerated pressure was associated with a 50% reduction in RV stroke volume. The highest pulmonary arterial occlusion pressure resulted in a doubling of MBF to all regions of the heart (266 +/- 99 to 504 +/- 158, 193 +/- 69 to 387 +/- 100, and 171 +/- 66 to 338 +/- 134 ml/min/100 g for the RV, septum, and left ventricle, respectively). The best correlation for increases in both RV and global MBF was the RV heart rate-systolic pulmonary pressure product. Adenosine infusion was associated with a threefold increase in global MBF that was significantly greater than the MBF achieved during pulmonary arterial occlusion. CONCLUSIONS: The fetal RV sensitivity to acute pressure loading is not associated with limitation of MBF. The fetal myocardium has a remarkable flow reserve that allows for preservation of function during acute increases in arterial pressure. PMID- 1638724 TI - Sustained protection by acadesine against ischemia- and reperfusion-induced injury. Studies in the transplanted rat heart. AB - BACKGROUND: We have shown that acadesine (AICAr: 5-amino-4-imidazole carboxamide riboside) improves the early recovery of function of the ischemic and reperfused rat heart. In the present studies we used the transplanted rat heart, with reperfusion for up to 24 hours, to assess whether the beneficial effect of acadesine is a transient or a sustained phenomenon (i.e., to determine whether the drug improves the extent of recovery or only the rate). METHODS AND RESULTS: Hearts (n = 8 per group) were excised and immediately arrested with an infusion (2 minutes at 20 degrees C) of the St. Thomas' Hospital cardioplegic solution with or without the addition of acadesine (20 mumol/l). They were then subjected to 4 hours of global ischemia (20 degrees C), and the cardioplegic solution (with or without acadesine) was infused for 2 minutes every 30 minutes. The hearts then were transplanted (1 hour additional ischemic time) into the abdomens of recipient rats, which had been given acadesine (100 mg/kg i.v.) or saline. They were reperfused in situ for 30 minutes or 24 hours and then excised and perfused aerobically for 20 minutes. Contractile function was assessed, and the hearts were taken for metabolite analysis. Two sets of four groups (n = 8 per group) were studied (one set with 30 minutes and the other with 24 hours of reperfusion): group A, acadesine-free control; group B, acadesine during cardioplegia alone; group C, acadesine during reperfusion alone; and group D, acadesine during both cardioplegia and reperfusion. With 30 minutes of reperfusion, a significant improvement in functional recovery was seen in the two groups (groups B and D) in which acadesine had been added to the cardioplegic solution. Left ventricular developed pressure (LVDP) at 12 mm Hg of left ventricular end-diastolic pressure (LVEDP) was 104 +/- 3 mm Hg in both groups versus 88 +/- 3 mm Hg in the acadesine-free controls (p less than 0.05). No protection was observed after 30 minutes of reperfusion when acadesine had been added during reperfusion alone (89 +/- 4 mm Hg). In contrast, after 24 hours of reperfusion there was a significant improvement in postischemic LVDP in all acadesine-treated groups (group B, 104 +/- 6 mm Hg; group C, 106 +/- 7 mm Hg; and group D, 117 +/- 3 mm Hg versus only 73 +/- 6 mm Hg in the acadesine-free controls; p less than 0.05 in each case). Metabolite analysis indicated that at the end of ischemia ATP was less depleted and levels of tissue adenosine were higher in the acadesine group. During early (30 minutes) reperfusion, acadesine produced higher mean ATP contents, although this achieved a level of statistical significance only when the drug was administered during both cardioplegia and reperfusion. After 24 hours of reperfusion, the adenine nucleotide pools were similar in all groups. CONCLUSIONS: Acadesine can afford sustained functional protection against injury during extended periods of ischemia and reperfusion. We present evidence that the beneficial effect of acadesine may be mediated by two different components, with one operative during ischemia and early reperfusion and the other acting later in the reperfusion period. PMID- 1638725 TI - Acadesine and myocardial protection. Studies of time of administration and dose response relations in the rat. AB - BACKGROUND: Although there are many factors that might contribute to tissue injury during ischemia and reperfusion, the loss of adenine nucleotides has long been considered to be of importance. This has led to the study of interventions designed to limit the loss of nucleotides or to enhance the rate of nucleotide resynthesis during reperfusion. Alternatively, the breakdown of adenosine triphosphate to adenosine might represent a protective response of the ischemic heart because adenosine is considered an anti-injury autocoid. Augmentation of endogenous adenosine levels might be beneficial. For these reasons, the protective properties of acadesine (AICAr: 5-amino-4-imidazole carboxamide riboside) were assessed in a rat model of myocardial ischemia and reperfusion. METHODS AND RESULTS: The protective properties of acadesine were studied in the isolated, perfused rat heart subjected to global hypothermic (20 degrees C) ischemia and reperfusion. When acadesine was given as an in vivo pretreatment (100 mg/kg i.v. 15 minutes before study) followed by being administered as an additive (20 mumol/l) to the St. Thomas' Hospital cardioplegic solution (single dose) and then as an additive (20 mumol/l) to the initial reperfusion (15 minutes) solution, the recovery of aortic flow after 2.5 hours of ischemia was improved from its control value of 16.5 +/- 3.9 ml/min to 28.9 +/- 4.1 ml/min (n = 8 per group; p less than 0.05). Similar protection was seen with other indexes of cardiac function. Analysis of hearts obtained at the end of 2.5 hours of ischemia and 35 minutes of reperfusion revealed no significant differences in metabolite content between control and drug-treated hearts with the exception of inosine monophosphate, which was increased from its drug-free control value of 0.10 +/- 0.01 mumol/g dry wt to 0.86 +/- 0.06 mumol/g dry wt (p less than 0.05). In further studies (n = 8 per group), with multidose (every 30 minutes) cardioplegia and extended periods (6 hours) of hypothermic ischemia, acadesine consistently led to higher mean recoveries of function and lower levels of creatine kinase leakage. Again, the only significant metabolic effect was an increase in tissue inosine monophosphate content. In studies (n = 12 per group) to determine whether acadesine was acting before, during, or after ischemia, the drug was given 1) only as pretreatment (100 mg/kg i.v.), 2) only during single dose cardioplegia (20 mumol/l), or 3) only during reperfusion (20 mumol/l). Significant protection was observed in the first two groups (recovery of aortic flow increased from 10.6 +/- 2.6 ml/min in the acadesine-free control to 22.6 +/- 2.8 and 23.6 +/- 3.1 ml/min, respectively; p less than 0.05). No significant protection was observed when acadesine was given only during reperfusion. In dose response studies, acadesine (0, 5, 20, 50, 200, and 1,000 mumol/l; n = 12 per group) was given only as a cardioplegic additive; the postischemic recoveries of aortic flow were 15.4 +/- 2.8, 16.9 +/- 3.6, 29.5 +/- 3.8, 27.4 +/- 3.8, 26.7 +/- 4.2, and 27.1 +/- 2.7 ml/min, respectively. CONCLUSIONS: Acadesine improves the ability of the heart to recover from ischemia and reperfusion when administered before ischemia or with cardioplegia. The mechanism underlying the protection remains to be resolved. PMID- 1638726 TI - Pleural effusion as a cause of right ventricular diastolic collapse. AB - BACKGROUND: We hypothesized, after seeing several suggestive clinical examples, that a process leading to a large bilateral pleural effusion in the presence of an otherwise insignificant pericardial effusion could result in right ventricular diastolic collapse (RVDC) as seen by two-dimensional echocardiography. This noninvasive marker for hemodynamically significant cardiac tamponade occurs when pericardial fluid is under pressure. Therefore, RVDC resulting from a large pleural effusion would represent a false-positive indication of cardiac tamponade caused by excessive pericardial fluid. METHODS AND RESULTS: Seven spontaneously breathing dogs were chronically instrumented to measure ascending aortic, right atrial, intrapericardial, intrapleural, left atrial, and pulmonary artery pressures and cardiac output. Intravascular volume was adjusted before each experiment to the euvolemic range with saline solution. The onset of RVDC was observed in each animal by two-dimensional echocardiography during seven paired episodes of tamponade induced by infusions of warm saline into the pericardial space alone and, after drainage of the pericardial fluid and complete recovery, into the pleural space in the presence of a small pericardial effusion. The onset of RVDC occurred at the same intrapericardial (8.17 versus 9.47 mm Hg) and right atrial (7.41 versus 7.46 mm Hg) blood pressures regardless of whether it was produced by an intrapericardial or an intrapleural effusion but began in expiration during the former and in inspiration during the latter. Intrapericardial pressure increased in the same manner as intrapleural pressure during intrapleural saline infusion. Nevertheless, cardiac output and aortic blood pressure were better preserved, and at the onset of RVDC, the pulmonary artery systolic blood pressure was higher (p less than 0.0001) and the degree of pulsus paradoxus lower (p less than 0.01) with intrapleural infusion. CONCLUSIONS: These results indicate that a large bilateral pleural effusion can elevate intrapericardial pressure sufficiently to cause RVDC and, perhaps, lead to misdirected therapy of an otherwise insignificant pericardial effusion. PMID- 1638727 TI - Mechanism of double potentials recorded during sustained atrial flutter in the canine right atrial crush-injury model. AB - BACKGROUND: During atrial flutter, double potentials may be recorded at specific sites in the atria. It has been suggested that double potentials represent sequential activations at the center of the reentrant circuit. An alternative hypothesis is that double potentials represent electrical activity in an area of slow conduction. Understanding their mechanism is important because double potentials have been considered a possible indicator of target sites for catheter ablation. METHODS AND RESULTS: We systematically studied double potentials in our canine model of atrial flutter produced by right atrial crush injury using a 64 channel computerized mapping system with 56 electrodes on the right atrium in seven mongrel dogs under general anesthesia. Activation maps were recorded during sinus rhythm before and after crush injury, during rapid pacing above and below the crush injury, and during sustained atrial flutter, entrainment of atrial flutter, and termination of atrial flutter induced with D-sotalol (2 mg/kg). During sinus rhythm before crush injury, activation was uniform, and double potentials were not recorded in any dog. After crush injury, activation proceeded up to and around the crush injury, and narrowly split double potentials were recorded in two of seven dogs. During rapid pacing above and below the crush injury, double potentials were recorded in five dogs. During 14 episodes of atrial flutter (mean cycle length, 140 +/- 16 msec), double potentials were recorded at electrodes along the crush injury. The activation time of the early x component of the double potentials (25 +/- 13 msec) was similar to that of adjacent electrodes above the crush injury (24 +/- 11 msec), and the activation time of the late y component (89 +/- 13 msec) was similar to that of adjacent electrodes below the crush injury (91 +/- 14 msec). The timing of the x and y components was dependent on the location of the recording electrode, with x and y widely spaced at the end of the crush injury near the area of earliest atrial activation during atrial flutter, more equally timed at the center of the crush injury, and more closely timed at the end of the crush injury opposite the area of earliest activation. During transient entrainment, double potentials were accelerated to the pacing rate, but their activation time relative to adjacent electrodes was maintained. During abrupt termination of atrial flutter, the early x component of the double potential was always recorded, but the late y component was not, because of conduction block below the posterior end of the crush injury. CONCLUSIONS: This study has shown in our canine model of atrial flutter that double potentials are recorded from the center of the reentrant circuit and that they represent sequential activations as the reentrant wave front passes on either side of the crush injury. PMID- 1638728 TI - Abnormal laterality and congenital cardiac anomalies. Relations of visceral and cardiac morphologies in the iv/iv mouse. AB - BACKGROUND: In the management of hearts with deranged laterality, it is essential that the left and right atrial chambers are correctly identified. There are two major approaches, which are based on venous connections or on the morphology of the atrial appendages, and there is no consensus as to which is the most useful. We used the iv/iv mouse mutant, which is known to be pertinent to this problem, to evaluate the relations of cardiac defects with atrial, venous, and other visceral morphologies. METHODS AND RESULTS: The morphology of the heart and other organs was examined in 275 iv/iv mice using criteria based on abnormal laterality in humans. The arrangement of the atrial appendages was determined by morphological examination of the junction between the appendage and the venous component of the atrium. On this basis, 45.1% of cases were shown to have usual atrial arrangement, 50.2% had mirror imagery, 1.5% had right isomerism, and 3.3% had left isomerism. Every case of atrial isomerism had a cardiac lesion; the morphological types were similar to those seen in human cases. Of cases with either usual or mirror-image arrangement of the appendages, 33.2% had abnormal spleens, but only 3.1% had cardiac defects. Similarly, venous abnormalities were much more common (30.1%) than cardiac defects. CONCLUSIONS: Study results endorse the importance of the morphology of atrial appendages in predicting cardiac abnormalities and point to the marked inconsistency of the arrangement of other organs, including the spleen and the connections of the systemic veins. PMID- 1638729 TI - Influence of loading conditions and contractile state on pulmonary venous flow. Validation of Doppler velocimetry. AB - BACKGROUND: Although recent studies suggest that pulmonary venous flow velocities may be used to evaluate left ventricular diastolic function, the influence of loading conditions and contractile state on the magnitude and pattern of pulmonary venous flow are poorly understood. METHODS AND RESULTS: Fourteen anesthetized open-chest mongrel dogs were instrumented with pulmonary venous flow probes, atrial sonomicrometer crystal paris, and high-fidelity micromanometers; transesophageal Doppler echocardiography was used to obtain simultaneous pulmonary venous flow velocities. Measurements were made over a wide range of left atrial pressure obtained by either intravascular volume infusion and inferior vena caval balloon inflation (n = 8), halothane inhalation (n = 6), or phenylephrine infusion (n = 5). There was an excellent correlation for pulmonary venous systolic (J) to diastolic (K) time integral between the Doppler and flow probe signal (r = 0.94; SEE, 0.18). When left atrial pressure was increased by volume infusion, there was a significant linear relation between mean left atrial pressure and the Doppler J/K peak (r = 0.64; SEE, 3.4 mm Hg) and flow velocity time integral ratio (r = 0.75; SEE, 2.9 mm Hg). By contrast, when left atrial pressure was elevated by halothane-induced cardiac depression, there was no correlation. The independent determinants of the pattern of pulmonary venous flow (stepwise multiple linear regression analysis) under all conditions were atrial systolic shortening, aortic systolic pressure, heart rate, and left ventricular end-systolic dimension (cumulative r = 0.80). CONCLUSIONS: The pattern of pulmonary venous flow can be measured accurately with Doppler velocities and is differentially influenced by loading conditions and myocardial contractile state; in the absence of myocardial contractile dysfunction, the pattern of pulmonary venous flow may provide an estimate of left atrial pressure; and pulmonary venous flow is determined largely by atrial systolic function. PMID- 1638730 TI - Chronic reduction of myocardial ischemia does not attenuate coronary collateral development in miniswine. AB - BACKGROUND: Myocardial ischemia is considered to be a possible stimulus for development of the coronary collateral circulation. We therefore hypothesized that chronic reduction of myocardial oxygen demand to lessen ischemia would attenuate coronary collateral development over an 8-week period using left circumflex coronary artery (LCx) ameroid-induced constriction in pigs. METHODS AND RESULTS: Collateral development was assessed by myocardial blood flow (radioactive microspheres) and left ventricular regional function (sonomicrometer dimension gauges). beta-Adrenoceptor blockade with propranolol (160 or 320 mg b.i.d.p.o.) was initiated in 15 animals 1 day after surgery. Compared with 16 untreated animals, beta-adrenoceptor antagonism was documented in the treated group by 1) pharmacological stimulation with isoproterenol, 2) physiological stimulation during graded treadmill exercise, and 3) repeated long-term biotelemetry recordings of oxygen demand (heart rate and blood pressure) and regional myocardial function. In addition to pharmacological and physiological verification of beta-blockade, biotelemetry showed that, compared with the untreated animals, propranolol significantly reduced the daily number, individual duration, and severity of events representing myocardial dysfunction. This suggests that in the beta-blocked group, little if any ischemia was present throughout the first 5 weeks when collateral growth occurs. Transmural myocardial blood flow (expressed as a ratio of flow in the LCx region to the nonoccluded region of the left ventricle) and systolic wall thickening in the LCx region were determined at rest and during treadmill exercise (240 beats per minute) 31-38 days (5 weeks) and 60-67 days (8 weeks) after surgery. Propranolol was withdrawn 3 days before flow and function determinations and was resumed immediately after testing. Blood flow ratios at 5 weeks decreased similarly from rest to exercise in the untreated (0.83 +/- 0.04 to 0.60 +/- 0.05, p less than 0.05) and beta blockade group (0.82 +/- 0.09 to 0.57 +/- 0.10, p less than 0.05). Systolic wall thickening from rest to exercise was attenuated to the same degree in the untreated (59 +/- 6% to 38 +/- 6%, p less than 0.05) and beta-blockade group (50 +/- 8% to 30 +/- 5%, p less than 0.05). Similar flow and function responses were observed in both groups at 8 weeks. CONCLUSIONS: We conclude that growth and development of the coronary collateral circulation measured functionally during exercise at 90% of maximal heart rate is unrelated to the extent and duration of myocardial ischemia in this model. PMID- 1638731 TI - PEG-SOD and myocardial protection. Studies in the blood- and crystalloid-perfused rabbit and rat hearts. AB - BACKGROUND: Polyethylene glycol, covalently linked to superoxide dismutase (PEG SOD), has a long plasma half-life (greater than 30 hours) and has been proposed as an effective agent for reducing free radical-mediated injury ischemia and reperfusion. METHODS AND RESULTS: Using an isolated rabbit heart perfused with arterial blood from a support rabbit, we have demonstrated that pretreatment with PEG-SOD (30,000 units/kg, intravenous bolus, 12-24 hours before 60 minutes of normothermic global ischemia), combined with addition of PEG-SOD to the blood perfusion circuit (30,000 units/kg to the support rabbit) and inclusion of PEG SOD (150 micrograms/ml) in a cardioplegic solution, enhanced the postischemic recovery of left ventricular developed pressure (LVDP) from 51 +/- 6 to 74 +/- 9 mm Hg (p less than 0.05; n = 9 per group). In further studies we showed that, whereas maximum protection was obtained when PEG-SOD was given as a combined pretreatment and additive to both the cardioplegic and the reperfusate solutions (postischemic LVDP recovery increased from 44 +/- 4% in the control group to 70 +/- 3% in the PEG-SOD group), the administration of PEG-SOD during pretreatment plus cardioplegia or during reperfusion alone also resulted in a significant improvement in postischemic function (62 +/- 7% and 60 +/- 3%, respectively). However, the use of PEG-SOD as a cardioplegic additive alone failed to afford protection (47 +/- 4% recovery of LVDP). In dose-response studies (with 0, 3,000, 6,000, 12,000, 30,000, or 60,000 units/kg; n = 8 per group), maximum recovery of LVDP was obtained with the administration of 12,000 units/kg of PEG-SOD. Studies of the plasma activity of PEG-SOD confirmed its long half-life and showed that the treatment with PEG-SOD either 1 hour or 12-24 hours before the study resulted in similar levels of plasma activity. In an attempt to assess any involvement of blood-borne elements in the protection afforded by PEG-SOD, studies were also carried out in the crystalloid-perfused rabbit heart, and no protection was observed. Similarly, no protection was observed at any one of a variety of doses in the crystalloid-perfused rat heart. CONCLUSIONS: PEG-SOD can afford protection in the blood-perfused rabbit heart; this protection is dose dependent and probably involves some action of PEG-SOD on blood-borne elements, possibly leukocytes. PMID- 1638732 TI - An approach to evaluating thrombolytic therapy in acute myocardial infarction. The 'unsatisfactory outcome' end point. PMID- 1638733 TI - Risk, genotype, and cardiovascular disease. PMID- 1638734 TI - Evolution, evaluation, and efficacy of implantable cardioverter-defibrillator technology. PMID- 1638736 TI - Insurability of the adolescent and young adult with heart disease. Report from the Fifth Conference on Insurability, October 3-4, 1991, Columbus, Ohio. AB - By the mid-1990s there will be more than 500,000 young adults in the United States over the age of 21 with a cardiac malformation. Presently more than half of this population is denied insurance coverage entirely or in part because of their preexisting condition. Because some did not have coverage and because of uncertainty about whom to see for their cardiology care, patients assessed in NHS II who were evaluated by their physician on an annual basis before the age of 21 were seen by a cardiologist only every 10 years after the age of 21. However, they have been shown by NHS-II to be well-educated, productive in the workplace, and to share an equal place in society with the general population. Their health care costs are decidedly lower after the age of 21 than before. This group represents a microcosm of a general society of more than 37 million Americans who, for various reasons, are not insured. Dr. Wiener described an American health-care system in crisis. Smaller companies are no longer able to afford health insurance for all their employees, especially for those with preexisting conditions, because of an industry pricing concept based on a claims-experience standard rather than a community standard. The insurance industry, the government, and patients are demanding medical cost-containment. Health-care costs, 12.2% of the gross national product in 1990, are climbing, and no end to this increase is presently in sight.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1638735 TI - Environmental tobacco smoke and cardiovascular disease. A position paper from the Council on Cardiopulmonary and Critical Care, American Heart Association. AB - Although the number of cardiovascular deaths associated with environmental tobacco smoke cannot be predicted with absolute certainty, the available evidence indicates that environmental tobacco smoke increases the risk of heart disease. The effects of environmental tobacco smoke on cardiovascular function, platelet function, neutrophil function, and plaque formation are the probable mechanisms leading to heart disease. The risk of death due to heart disease is increased by about 30% among those exposed to environmental tobacco smoke at home and could be much higher in those exposed at the workplace, where higher levels of environmental tobacco smoke may be present. Even though considerable uncertainty is a part of any analysis on the health affects of environmental tobacco smoke because of the difficulty of conducting long-term studies and selecting sample populations, an estimated 35,000-40,000 cardiovascular disease-related deaths and 3,000-5,000 lung cancer deaths due to environmental tobacco smoke exposure have been predicted to occur each year. The AHA's Council on Cardiopulmonary and Critical Care has concluded that environmental tobacco smoke is a major preventable cause of cardiovascular disease and death. The council strongly supports efforts to eliminate all exposure of nonsmokers to environmental tobacco smoke. This requires that environmental tobacco smoke be treated as an environmental toxin, and ways to protect workers and the public from this health hazard should be developed. According to a 1989 Gallup survey commissioned by the American Lung Association, 86% of nonsmokers think that environmental tobacco smoke is harmful and 77% believe that smokers should abstain in the presence of nonsmokers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1638737 TI - Distribution and expression of G-protein in rat cerebral cortical cells. I. Intact tissue. AB - Localization and developmental expression of guanine nucleotide-binding regulatory protein (G-protein) were investigated in cerebral cortical tissue of rat. Immunohistochemical techniques using a rabbit polyclonal antibody were applied to reveal the pattern of G-protein distribution. Fluorescent staining in cortical sections was localized mainly to neurons; cell bodies were stained along with the proximal region of processes, including apical dendrites. All neurons appeared to be equally stained, and thus the staining activity reflected the laminar pattern of these cells in cortex. Moreover, areas of neuropil, white matter, and layer I were immunonegative, although synaptic labelling could not be directly eliminated. Most glial cells also lacked staining; however, moderately intense labelling was observed in the choroid plexus, ependymal cells and a subpopulation of microglia. Using Western immunoblot analysis, the antigens recognized in rat cerebral cortex were shown to co-electrophorese with the alpha- and beta-subunits of bovine brain G-protein, thus supporting the specificity of the antibody preparation utilized. In contrast to the adult tissue, in fetal and neonatal cortex faint to moderate staining was uniformly exhibited by essentially all cells. As determined by the immunoblot procedure, the overall level of G protein increased from the fetal stage through the neonatal and adolescent periods to reach a maximum concentration in young adult tissue. Based on cellular distribution, G-protein may function in the overall regulation of neuronal activity within cerebral cortex. Further, these results suggest that there is a selective developmental increase in expression of G-protein in specific cell populations, particularly neurons. PMID- 1638738 TI - Cytoarchitectonic abnormalities in hippocampal formation and cerebellum of dreher mutant mouse. AB - The laminated structures in the hippocampal formation and cerebellum of homozygous dreher mice were compared to their littermates and to C57BL/6J mice in Nissl- and myelin-stained preparations. In the dreher dentate gyrus, ectopic granule cells were situated in the molecular layer, and frequently there was either partial or complete absence of the infrapyramidal limb of the granule cell layer. In the dreher hippocampus, the cells of the pyramidal cell layer in area CA3 formed widely dispersed arrangements, and there were ectopically situated pyramidal cells in the stratum radiatum and stratum oriens. In the dreher cerebellum, 3 abnormal patterns were observed: (1) disruptions of foliation with normal cytoarchitectonic structure, (2) foliation with a mixture of normal laminated structure and abnormal laminated structure, and (3) almost complete absence of the cerebellum. In abnormal folia exhibiting the second or third pattern, islands consisting of agglomerations of both granule cells and Purkinje cells or just granule cells were observed. The neuronal heterotopias and cytoarchitectonic disorganization observed in the present study are apparently secondary to disruption of cell proliferation and neuronal migration produced directly or indirectly by the dreher mutation. In addition, the fact that the phenotypic abnormalities in homozygous dreher mice produces different abnormal morphologies in different specimens may be useful for analyzing the development of the hippocampal formation and cerebellum. PMID- 1638739 TI - Distribution and expression of G-protein in rat cerebral cortical cells. II. Primary tissue culture. AB - In continuing an assessment of the cellular distribution and developmental expression of brain guanine nucleotide-binding protein (G-protein) (Go), this component was investigated in primary cultures of dissociated cerebral cortical cells derived from fetal rat. Using a polyclonal antibody recognizing brain Gi/Go, G-protein was detected through immunohistochemical staining and a Western immunoblot procedure. In initial studies, the presence of G-protein in cultures containing mature cells was demonstrated using the immunoblot technique; this G protein corresponded predominately to the Go form as the alpha- and beta-subunits were revealed, and these co-migrated with similar antigens from the intact tissue and of purified bovine brain G-protein. The pattern of cellular localization or distribution in stained cultures was very similar to that observed in vivo, as differentially high staining was present in neurons, ependymal cells and microglia. In neurons, the immunofluorescent staining was relatively uniform over the cell body and at least the initial segment of processes. When cultures of different ages were assessed, the G-protein exhibited a developmental pattern of increase in expression similar to that observed in whole tissue, as determined by immunoblotting. The cortical cultures reflect the distribution and expression of G-protein in vivo and, thus, specific cell types therein may be useful in investigating the functional role of the predominate type of this protein in brain tissue (Go). PMID- 1638740 TI - The effects of systemic morphine on behavior and EEG in newborn rats. AB - Early studies suggested that newborn animals are far more susceptible to the convulsant effect of systemic morphine than adult animals. The present study reassessed morphine's (0, 6, 12.5, 25, 50, 100 and 300 mg/kg) toxic effects, making use of electroencephalographic (EEG) recordings, behavioral observations and the specific opiate antagonist naloxone in immature rats (postnatal days 1, 3, 6, 12 and 24). Although morphine had opiate-specific effects (such as inhibition of activity at low doses), non-specific effects (such as hyperactivity) elicited by the highest doses, predominated in the 3 youngest age groups. At day 12 high doses of morphine first produced Straub tail and catatonia. At this age morphine produced EEG spikes that were not reversed by naloxone. Only at day 24 were electrographic spikes temporarily inhibited by naloxone. Behavioral convulsions were never observed, at any age. These findings indicate that morphine is less toxic in newborns than suggested previously. PMID- 1638741 TI - Microglial cell response to neuronal degeneration in the brain of brindled mouse. AB - Reactive changes of microglia in response to neuronal degeneration were investigated in the brains of brindled mottled mice with immunocytochemical technique. This mutant has a genetic defect in copper metabolism and spontaneous neuronal degeneration develops around postnatal day 10, in particular in the parasagittal regions of the cerebral cortex and thalamus. The antibodies to macrophage specific antigen, F4/80 and to type-three complement receptor, Mac-1 were used for the study. Reactive morphological changes of microglia, which are immuno-reactive to the antibodies to F4/80 and/or Mac-1, were demonstrated in areas corresponding to those of neuronal degeneration, coincident with the emergence of cells expressing major histocompatibility complex class II, Ia, antigen. Some of the Ia expressing cells had morphological features of ramified microglia, while others were rod shaped with few processes and were mostly located in the perivascular regions. The focal nature of such cellular changes suggests that signal(s) from the degenerating neurons may be responsible for microglial activation and cellular expression of the Ia antigen in the brain of the brindled mouse. PMID- 1638742 TI - Refinement of dendritic arbors along the tonotopic axis of the gerbil lateral superior olive. AB - We have investigated the development of dendritic arbors in a central auditory nucleus in the Mongolian gerbil, the lateral superior olive (LSO). The morphology of these arbors has been shown to vary with tonotopic position in adults, with high frequency neurons having a more restricted field. In the present study, qualitative observations were made on horseradish peroxidase-filled neurons from animals 1-11 days postnatal, and quantitative results were obtained from Golgi impregnated material from animals 10 days postnatal and older. The tonotopic position of each cell was computed as a percent of the total distance along the LSO. The dendritic arbors of high frequency neurons became spatially constrained along the frequency axis during the 3rd postnatal week, while those in the low frequency region retained a broader arborization into adulthood. This refinement was correlated with a decrease in total dendritic length and the number of branch points per neuron, particularly in the high frequency projection region. The distribution of octave bandwidths to which single LSO neurons responded in 13-16 day animals showed a similar course of maturation across the tonotopic axis: high frequency neurons responded to a larger number of octaves, and with greater variability, than those in adults. These data suggest that a specific alteration in dendrite morphology, which occurs after the onset of response to airborne sound, may contribute to adult frequency selectivity. PMID- 1638743 TI - Pyramidal neurons in immature rat hippocampus are sensitive to beta-adrenergic agents. AB - The development of hippocampal neuronal sensitivities to the beta-noradrenergic agent, isoproterenol, was examined in tissue from immature rats. The in vitro hippocampal slice preparation was used to assess intracellularly recorded responses from hippocampal neurons to pressure-pulse and bath application of noradrenergic drugs. Effects of the drug on individual hippocampal CA3 pyramidal neurons were compared across several stages of development, ranging from postnatal day 4-5 (P4-5) to maturity. Isoproterenol, pressure-pulse applied to CA3c pyramidal cells, produced a depolarization of membrane potential and an increase in cell input resistance in tissue as young as P7. Spike frequency adaptation (in trains of action potentials triggered by depolarizing pulses) was reduced, as were the slow after-hyperpolarizations following the spike trains. All agonist effects were blocked by timolol, a beta-antagonist. Drug-induced changes in cell membrane and firing properties in immature tissue were qualitatively similar to beta-receptor-mediated noradrenergic effects in adult tissue. These results indicate that the beta-receptor-mediated component of the noradrenergic effect in rat hippocampus is physiologically functional by the seventh day of postnatal life; at earlier times (P4-5) these beta-receptor mediated noradrenergic actions are, at best, equivocal. PMID- 1638744 TI - Environmental enrichment, neocortical ectopias, and behavior in the autoimmune NZB mouse. AB - New Zealand Black (NZB) mice have severe autoimmune disease and approximately 40% have cortical ectopias in layer I of sensorimotor cortex. Because the ectopias are similar to those found in dyslexics, NZB mice have been used as an animal model for developmental learning disorders. In addition, these mice have been used as a model of learning deficits associated with autoimmune disease. To determine whether early intervention would affect learning processes in NZB mice, they were reared after weaning in standard cages or enriched environments. They were given a battery of behavioral tests to measure learning, laterality, and activity, after which they were sacrificed and their brains examined for cortical ectopias. The tests sorted into two behavioral sets. Ectopia-associated behaviors included black-white discrimination learning and the Morris spatial maze. As a group, the mice performed well on these tasks. Ectopic mice had poorer performance than non-ectopics on these measures, and environmental enrichment countered the effects of the ectopias. Autoimmune-associated behavior involved two-way avoidance learning in a shuttlebox. Mice were uniformely poor on this task, ectopias did not affect behavior, and environmental enrichment was without benefit. Evidence from this and other studies shows that poor shuttlebox performance is related to the presence of autoimmune disease. Thus, autoimmune disease and cortical ectopias each appear to affect a separate set of behavioral processes. Environmental enrichment is most effective for behavioral impairments mediated via cortical ectopias, but is much less effective, if at all, if autoimmunity is the primary mediator of the impairments. PMID- 1638745 TI - Possible role for chondroitin sulfate in urolithiasis: in vivo studies in an experimental model. AB - The effect of chondroitin sulfate upon the growth of calcium oxalate crystals was measured in vivo by using an experimental model in rats. Adult male Wistar rats were treated by chronic i.p. injections of chondroitin sulfate solutions (1, 5 or 10 mg in 0.3 ml of saline, every 2 days). This treatment led to a dose-dependent increase in the urinary chondroitin sulfate concentration. Urolithiasis was induced by the introduction of a calcium oxalate seed into the bladder of the animals. Urine samples were collected and the calculi formed were removed after 42 days. The chondroitin sulfate concentration have decreased in the lithiasic urines, as compared to controls and higher chondroitin sulfate doses correlated with larger calculi. The presence of chondroitin sulfate in the matrices of stones obtained from chondroitin sulfate-treated animals suggested that there was some adsorption of chondroitin sulfate on to the growth sites of the calcium oxalate crystals. In contrast to the chondroitin sulfate effect observed in vitro, which inhibits the growth of calcium oxalate crystals, our results suggest that in vivo chondroitin sulfate promotes the growth of stones in the urinary tract. PMID- 1638746 TI - Abnormal lysosomal cathepsin activities in leukocytes and cultured skin fibroblasts in late infantile, but not in juvenile neuronal ceroid-lipofuscinosis (Batten disease). PMID- 1638747 TI - Liquid chromatography determination of alpha-tocopherol in erythrocytes. PMID- 1638748 TI - Fetal and amniotic alpha 1-acid glycoprotein. PMID- 1638749 TI - A method for quantitative collection of stool and urine for nitrogen balance studies in infants. PMID- 1638750 TI - Rapid and sensitive colloidal silver staining on cellulose acetate membranes. PMID- 1638751 TI - The effect of reducing and non-reducing sugars on the bicinchoninic acid reaction for protein determination. PMID- 1638752 TI - Procedure for development of an enzyme-linked immunosorbent assay. Development of an assay for human apolipoprotein A-I. AB - A set of criteria for selection of antibodies during the development of enzyme linked immunosorbent assay (ELISA) is described. Using these criteria, a competitive ELISA for human apo A-I using a polyclonal goat antibody was developed. The assay recognizes apo A-I from plasma and high-density lipoprotein (HDL), as well as the pure delipidated apo A-I, equally. Intra- and inter-assay variations were 5.2% and 3.5%, respectively. Recovery rate, as determined by spiking a known quantity of pure delipidated apo A-I into a reference plasma, was determined to be 101.3%. The assay was validated by comparing the concentration of apo A-I in HDL with the dye elution method. The apo A-I ELISA to apo A-I dye elution ratio was 1.01. Apo A-I concentration in Centers for Disease Control reference material determined by this method was in agreement with the reported consensus value. Repeated freezing and thawing of the samples (three freeze-thaw cycles at -20 degrees C) as well as long-term freezing (up to 1 year at -70 degrees C) did not affect the concentration of apo A-I in the samples. The assay was applicable both to normolipidemic and dyslipidemic plasmas. No immunologic difference was noted when plasma from dyslipidemic subjects was assayed. A frequent problem of long-term storage is deamidation. The values found for apo A I in a deamidated plasma were the same as those for the corresponding fresh plasma. Plasma apo A-I values were also positively correlated with that of HDL cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1638753 TI - 13C and 31P NMR studies of glucose and 2-deoxyglucose metabolism in normal and enzyme-deficient human erythrocytes. AB - The flux of 13C-labeled glucose through the Embden-Meyerhof and pentose phosphate pathways was studied by 13C NMR in intact erythrocytes isolated from normal subjects or from patients suffering of glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) deficiency. Similar rates of glucose catabolism and similar fluxes of the 13C-label into 2,3-bisphosphoglycerate and lactate were found, under basal conditions, in normal and in G6PD-deficient erythrocytes incubated in the presence of either [1-13C]- or D[6-13C]glucose. Exposure to oxidative stress by preincubation with tert-butylhydroperoxide induced in normal, but not in G6PD deficient erythrocytes, a significant enhancement of glucose consumption, as well as a substantial reduction in 13C-label transfer from C1-glucose into lactate. It was also possible, by 31P NMR, to evaluate the conversion of 2-deoxyglucose to its phosphate-containing metabolites. The oxidation and subsequent decarboxylation of 2-deoxyglucose-6-phosphate was assessed in reconstituted systems and could subsequently be evidenced also in ethanolic extracts from normal (but not from G6PD-deficient) erythrocytes which had been exposed to oxidative stress. The results indicate that, in terms of glucose flux through the glycolytic pathway, there is little or no difference between normal and G6PD deficient erythrocytes, regardless of previous exposure to oxidative stress. Faster consumption of either glucose or 2-deoxyglucose is induced, only in normal cells, by treatment with tert-butylhydroperoxide, essentially as a consequence of the activation of the pentose-phosphate pathway. PMID- 1638754 TI - Optimized determination of malondialdehyde in plasma lipid extracts using 1,3 diethyl-2-thiobarbituric acid: influence of detection method and relations with lipids and fatty acids in plasma from healthy adults. AB - We investigated the influence of different concentrations of Fe3+, phosphoric acid, butylated hydroxytoluene and glutathione on the production of the malondialdehyde-1,3-diethyl-2-thiobarbituric acid adduct in plasma lipid extracts. Following organic solvent extraction the stable product was analyzed by spectrophotometry (537 nm), fluorometry (547 nm) and high-performance liquid chromatography with fluorometric detection. Using optimized reaction conditions there was good agreement between the three methods, with slightly higher values for the spectrophotometric method. Plasma total lipid malondialdehyde reference values for 24 healthy adults amounted to 1.30 +/- 0.23 mumol/l (spectrophotometric method) and 1.11 +/- 0.31 mumol/l (fluorometric method). Plasma lipid malondialdehyde concentrations correlated significantly with plasma triglycerides (r = 0.527), total cholesterol (r = 0.612) and total fatty acids (r = 0.810) and with the total number of double bonds present in plasma fatty acids with three or more double bonds (r = 0.923). PMID- 1638755 TI - The glycosaminoglycan composition of the lung with acute and chronic pathology and in senescence. AB - The content and distribution of GAGs in the anatomic structures of pathological (pneumoconiosis, pneumonia, pulmonary embolism) and senescent lungs have been measured. The total GAG content of the lung structures, except central bronchi is generally lower than normal in the pathological lungs. The GAG distribution in the pleura (DS predominant), central bronchi (C6S predominant), arteries, veins and 'total lung' is similar to the corresponding normal distribution. The other notable observations are: the concentration of HA in peripheral bronchi and alveoli is increased possibly in response to the high local concentration of coal dust; an age related GAG switch from DS in the arteries of the young to C6S in the arteries of the mature lung is confirmed; the arterial GAG content generally increases with age up to age 103 in the male; the arteries of a female smoker display the mature male pattern of GAG composition. The data suggest that gender, smoking and age, more than acute pathology, determine the GAG composition of the anatomic structures of the lung. PMID- 1638756 TI - Determination of (S)- and (R)-2-oxo-3-methylvaleric acid in plasma of patients with maple syrup urine disease. AB - An enzymatic method for the separate measurement of both chiral 2-oxo-3 methylvaleric acid (OMV) compounds, (S)- and (R)-OMV, by NADH-dependent enantioselective amination using leucine dehydrogenase in the presence of a NADH regenerating system is described. This method allows the quantitative determination of all branched-chain 2-oxo acids, simultaneously. In plasma samples from classical maple syrup urine disease patients under therapy the average (R)-OMV/(S)-OMV ratio was 0.35 and great differences in the transamination equilibria of the diastereomeric branched-chain amino acids L isoleucine and L-alloisoleucine were demonstrated. PMID- 1638757 TI - Serum immunoreactive beta-glucuronidase determined by an enzyme-linked immunosorbent assay in patients with hepatic diseases. AB - An enzyme-linked immunosorbent assay (ELISA) was developed for human beta glucuronidase, using a specific polyclonal antibody raised against the purified enzyme. beta-Glucuronidase from human liver consisted of three subunits with molecular mass of 76, 64 and 18 kDa. The assay offered a specific, sensitive and convenient means of measuring immunoreactive beta-glucuronidase in human sera. beta-Glucuronidase activity determined by the conventional method appeared to be extremely low, indicating that in human sera beta-glucuronidase exists in an enzymatically inactive form. The sensitivity of the assay permitted the detection of 1-100 ng of purified beta-glucuronidase. A mean serum level in normal subjects was 108 +/- 25 ng/ml (mean +/- S.D.). A high level of beta-glucuronidase was found in sera of patients with severe hepatocellular necrosis, including liver cirrhosis (152 +/- 130 ng/ml) and chronic active hepatitis (220 +/- 99 ng/ml), whereas no significant increase of the enzyme protein was observed in chronic persistent hepatitis (102 +/- 42 ng/ml). beta-Glucuronidase was also increased in sera of patients with primary hepatoma (156 +/- 125 ng/ml). The immunoreactive beta-glucuronidase determined in this assay was thought to be a supplementary serological indicator for hepatocellular necrosis. PMID- 1638758 TI - An immunoreactive xanthine oxidase protein-possessing xanthinuria and her family. AB - The presence of immunoreactive xanthine oxidase protein was proven in a xanthinuric patient, using a polyclonal antibody against xanthine oxidase. The antibody was raised against purified human liver xanthine oxidase in a rabbit. Double immunodiffusion method demonstrated the existence of an immunologically reactive xanthine oxidase which did not possess xanthine oxidase activity. In addition, urinary excretion of oxypurines in the patient and her family was investigated. The results indicated that a brother and a sister had xanthinuria. PMID- 1638759 TI - A receptor assay for serum low density lipoprotein-apolipoprotein B-100: preliminary report. PMID- 1638760 TI - Experimental autoimmune uveoretinitis (EAU) versus experimental allergic encephalomyelitis (EAE): a comparison of T cell-mediated mechanisms. AB - EAU is a model of ocular inflammatory disease. EAU resembles another T cell mediated autoimmune disease--experimental allergic encephalomyelitis--since both have increased expression of MHC class II molecules in the target tissue, can be adoptively transferred by activated CD4+ T cells and are inhibited by cyclosporin A. The immunological findings will be compared to find out if the same cellular mechanisms are involved in both diseases. PMID- 1638761 TI - Rapamycin prevents the onset of insulin-dependent diabetes mellitus (IDDM) in NOD mice. AB - The effect of the immunosuppressive agent rapamycin (RAPA) was assessed in the non-obese diabetic (NOD) mouse which is an autoimmune model of IDDM. RAPA was prepared in a vehicle of 8% cremophor EL/2% ethanol and investigated in two studies. NOD/MrK female mice (six per group, study no. 1; 10 per group, study no. 2) were dosed three times per week p.o. by gavage from 56 to 170 days of age (study no. 1) or from 64 to 176 days of age (study no. 2). Mice treated with RAPA at 0.6 mg/kg, 6 mg/kg, or 12 mg/kg maintained normal plasma glucose through 170 or 176 days of age with 10%, 0%, and 0% incidence of diabetes respectively. In contrast, naive, vehicle-treated, or RAPA 0.06 mg/kg-treated mice exhibited elevated plasma glucose and disease incidence typical for female NOD mice. Mice which became diabetic had elevated levels of beta-hydroxybutyrate, triglycerides and cholesterol. These plasma lipid concentrations were positively correlated with the duration of hyperglycaemia (r = 0.85, 0.87 and 0.84 respectively). Outside of its ability to prevent diabetes, RAPA itself did not affect the lipid profile of the mice. Intervention therapy with RAPA was ineffective at reversing the course of disease after IDDM onset under these experimental conditions. Finally, we report here that prophylactic treatment with RAPA was able to protect against IDDM development in some RAPA-treated mice 41 weeks after cessation of treatment. These data show that orally administered RAPA is effective in preventing onset of disease in the NOD mouse, a relevant model of autoimmune type I diabetes in man. PMID- 1638762 TI - The effects of CP 17193, an immunosuppressive pyrazaloquinoline, on the development of spontaneous lupus disease in NZBW F1 hybrid mice. AB - The effects of the immunosuppressive agent CP 17193 on the development of spontaneous lupus disease in female NZBW F1 hybrid mice were investigated. Long term dosing with CP 17193 markedly delayed the onset of mortality but did not extend the long term survival of the mice. CP 17193 significantly inhibited immune complex deposition in the glomeruli of 30- and 35-week-old mice and also reduced the levels of proteinuria in the 35-week-old mice. There was a slight reduction in the levels of circulating antinuclear antibody to ds DNA in CP 17193 treated mice but this was not statistically significant. Studies on immune cell function of 35-week-old mice dosed with CP 17193 showed significant reduction in the total numbers of spontaneous polyclonal antibody producing cells. Analysis of the results revealed these effects to result from a marked reduction in total spleen cell numbers in CP 17193-treated mice. When results were expressed as activity per cell unit the differences between drug-treated and control mice were small. Spleen cells from mice given a shorter dosing schedule of 7 weeks with CP 17193 showed an augmentation of IL-2 production and responsiveness. These results show CP 17193 having interesting selective immunomodulating activity on the immunopathogenesis of spontaneous murine lupus disease. Furthermore, compounds with this profile of activity may have a potential role in the treatment of some autoimmune diseases. PMID- 1638763 TI - T cell heterogeneity in patients with common variable immunodeficiency as assessed by abnormalities of T cell subpopulations and T cell receptor gene analysis. AB - T lymphocyte regulation of immunoglobulin production may be abnormal in some patients with common variable immunodeficiency (CVI). Phenotypic analysis of peripheral blood T lymphocytes from nine patients with CVI was conducted to examine whether an abnormal distribution could be detected in a functionally distinct T lymphocyte subpopulation. The percentage of CD8+ lymphocytes proved to be increased in some patients and decreased in others. In comparison with normal controls, many patients with CVI had reduced percentages of lymphocytes expressing both CD4 and CD45RA, a phenotype associate with naive CD4+ cells. There was no significant difference in CD4+ populations bearing CD29 or leucocyte adhesion molecule-1 (LAM-1) antigens. The pattern of gene rearrangement of the T cell antigen receptor (TCR) was studied using peripheral blood lymphocytes from these patients with CVI. Genomic DNA from freshly isolated lymphocytes as well as from selectively propagated CD4+ or CD8+ populations were examined using Southern blot analysis and a probe for the beta chain of the TCR. A polyclonal pattern of TCR gene rearrangement, without the appearance of dominant non-germline bands, was demonstrated in all patient samples. These data suggest that the T lymphocytes in patients with CVI have a polyclonal pattern of TCR rearrangement despite an abnormal distribution of T cell subpopulations in some patients. PMID- 1638764 TI - Possible role of IL-2 deficiency for hypogammaglobulinaemia in patients with common variable immunodeficiency. AB - Common variable immunodeficiency (CVID) patients are unable to produce specific immunoglobulins after antigen contact in vivo. The aim of this study was to investigate whether in some cases of CVID a decreased de novo synthesis of IL-2 might be the cause of immunodeficiency and whether this deficiency can be corrected by IL-2 supplementation in vitro. Mononuclear cells from 17 CVID patients and from 10 healthy controls were cultured with monoclonal anti-CD3 antibody OKT3, pokeweed mitogen (PWM) or tetanus toxoid (TT) to stimulate IL-2 synthesis. In parallel, in vitro IgG and IgM synthesis was stimulated with Staphylococcus aureus Cowan I (SAC), PWM or TT in the presence or absence of IL 2. While lymphocytes of 11 out of 17 patients produced low to normal amounts of IL-2 upon stimulation with anti-CD3, only three patients showed low IL-2 production in response to PWM and five in response to TT. Regarding immunoglobulin synthesis in vitro, five patients completely failed to produce IgM or IgG upon stimulation with PWM, SAC or TT irrespective of the addition of IL-2. By contrast, four patients did not show any defect in vitro and synthesized normal amounts of IgM and IgG with any of the three stimuli. Finally, eight patients could be reconstituted for PWM-, SAC- and TT-induced IgM and/or IgG synthesis in vitro, by adding IL-2 to the culture system. This enhancing effect of IL-2 could be blocked by adding anti-IL-2 receptor antibodies to the cultures. Our findings indicate that a defective IL-2 synthesis after antigen stimulation may be one reason for the impaired immunoglobulin production in some cases of CVID. PMID- 1638765 TI - Raised serum neopterin levels in patients with primary hypogammaglobulinaemia; correlation to other immunological parameters and to clinical and histological features. AB - Serum neopterin levels were analysed in 43 patients with primary hypogammaglobulinaemia (25 common variable immunodeficiency (CVI), 12 congenital hypogammaglobulinaemia (CH), six X-linked hypogammaglobulinaemia (XLH)), and in 33 healthy controls. The neopterin values were correlated to lymphocyte subset counts in peripheral blood, lymphocyte mitogen responses and clinical and histological manifestations in the study group. Serum neopterin levels were significantly elevated in all subgroups of patients and particularly in the CVI groups where the highest concentrations were found (P less than 0.001, CVI versus controls). Furthermore, in CVI and CH patients elevated neopterin levels were strongly correlated to decreased number of CD4+ lymphocytes (rs = -0.61, P less than 0.005 and rs = -0.83, P less than 0.001, respectively). In the CVI group high neopterin levels were also significantly correlated to low number of circulatory B (CD19+) lymphocytes (rs = -0.58, P less than 0.05). Both patients with moderately and those with severely depressed lymphocyte mitogen responses had significantly higher neopterin levels than those with normal responses. In addition, high neopterin levels were significantly associated with the occurrence of splenomegaly and nodular intestinal lymphoid hyperplasia. The immunological findings were consistently observed in longitudinal testing, and appeared to be characteristic for the individual patient. High serum neopterin levels are thought to be a marker for hyperactivity in monocytes/macrophages, and dysfunction of these cells may therefore be associated with fundamental immune pathology in some subgroups of primary hypogammaglobulinaemia. PMID- 1638766 TI - Induction of experimental systemic lupus erythematosus (SLE) in mice with severe combined immunodeficiency (SCID). AB - A model in which experimental SLE is induced in normal mice by the injection of a human anti-DNA MoAb expressing a common idiotype 16/6 Id has been established in our laboratory. In the present study we have attempted the induction of experimental SLE in mice with SCID by the transfer of lymphocytes obtained from mice with experimental SLE. Disease could not be induced by direct immunization of SCID mice with the 16/6 Id nor by transfusion of normal splenocytes and immunization with the 16/6 Id thereafter. In contrast, disease was induced in SCID mice which were transplanted with splenic lymphocytes obtained from SLE afflicted BALB/c mice. The disease was expressed by the presence of high titres of antibodies and glomerular immune complex deposits were present in the kidney sections of these mice. Mice that received spleen cells from donors with experimental SLE together with the 16/6 Id developed higher titres of autoantibodies and had, in addition to the immune complex deposits, glomerular histological pathology. The model of experimental SLE induction in SCID mice should help in the elucidation of the role of different cell types in the pathogenesis of SLE. PMID- 1638767 TI - Acceleration of onset of collagen-induced arthritis by intra-articular injection of tumour necrosis factor or transforming growth factor-beta. AB - We examined whether tumour necrosis factor (TNF) or transforming growth factor beta 1 (TGF-beta 1) could alter the course of collagen-induced arthritis (CIA). Injection of 100 ng TNF or 500 ng TGF-beta 1 into ankle joints of normal rats induced a very limited inflammatory response, observable only upon histological analysis. However, when injected into ankle joints of rats 9 days after immunization with bovine type II collagen (CII), identical doses of TNF or TGF beta 1 induced a sustained, clinically obvious inflammation and oedema that began within 8 h on average, as compared to 90 h in CII-immunized control rats given no injections or intra-articular injections of buffer. The incidence of arthritis at 2 weeks post-immunization was 100% for TNF-injected hindpaws, compared with 55% for the control groups, a statistically significant difference. In rats passively immunized with a subarthritic dose of affinity purified antibody to rat-CII, intra-articular injection of 100 ng TNF or 500 ng of TGF-beta 1 also induced intense, though transient arthritis. The rapid proinflammatory effects in CIA described in this study and the synergy demonstrated between anti-CII IgG and either cytokine, suggest that these cytokines can participate locally in the pathogenesis of arthritis. PMID- 1638768 TI - Activation of IL-6 production by UV irradiation of blood mononuclear cells from patients with systemic lupus erythematosus. AB - Cultured mononuclear cells from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and normal donors were assayed for their ability to secrete IL-6 both spontaneously and after exposure to UV light. Mononuclear cells from SLE, RA and atopic control patients produced IL-6 spontaneously, while those from normal donors did not. Spontaneous production of IL-6 occurred in the non adherent cell population. UV light-induced IL-6 production was confined exclusively to the SLE patients and was present only in the macrophage/monocyte fraction. This stimulation was induced by wavelengths in the UVA, UVB but not the UVC portion of the spectrum. These results suggest that cytokine release may be involved in the exacerbations of SLE provoked by photosensitivity. PMID- 1638769 TI - Serum levels of IL-1, IL-6 and tumour necrosis factors in patients undergoing coronary artery bypass grafts or cholecystectomy. AB - Plasma levels of biologically active IL-1, tumour necrosis factor (TNF) and IL-6 were measured before, during and after coronary artery bypass graftings (CABG) (n = 9) and cholecystectomy (CHO, n = 9), and in normal controls (nine healthy volunteers). Mean pre-operative IL-1 concentration in four of the nine CABG patients was 0.452 + 0.03 ng/ml, significantly (P less than 0.001) higher than that of the other five (0.045 +/- 0.009 ng/ml), CHO patients (0.035 +/- 0.005 ng/ml) and controls (0.029 +/- 0.008 ng/ml). Three of the four patients with high pre-operative IL-1 had functional capacity IV, while the other five had functional capacity IIa or IIb. Slight IL-1 elevation after anaesthesia, followed by reduction after initiation of bypass, elevation on completion of surgery and reduction to basal levels after 7 days was found in patients undergoing CABG. Mean basal TNF levels of CABG and CHO patients did not differ, but were higher than those of controls (2.85 +/- 0.5 ng/ml for CABG, 2.05 +/- 0.06 ng/ml for CHO, 0.72 +/- 0.07 ng/ml for normals, P less than 0.001). A unique kinetics of release during CABG was observed also for TNF. Mean pre-operative IL-6 levels were normal (50 +/- 3 ng/ml for CABG, 50 +/- 0.5 ng/ml for CHO and 65 +/- 10 ng/ml for controls). Gradual elevation to a mean peak of 725 +/- 100 ng/ml on completion of CABG was observed as compared with 275 +/- 50 ng/ml in CHO (P less than 0.01). On the seventh post-operative day mean IL-6 levels returned to normal. Two patients with post-operative low-grade fever (38 degrees C) had high, late cytokine levels. One of these two patients had leucocytosis, sterile discharge from the operative wound and was diagnosed as suffering from the Dressler syndrome. In this study elevated cytokine values and unique kinetics of release into the serum were found in patients undergoing CABG. PMID- 1638770 TI - IL-4 and transforming growth factor-beta suppress human immunoglobulin secretion in vitro by surface IgD- B cells. AB - The effect of IL-4 and transforming growth factor-beta (TGF-beta) on immunoglobulin secretion in vitro by peripheral blood mononuclear cells (PBMC) or purified B cells activated with murine EL4 thymoma cells and phorbol myristate acetate (PMA) was investigated. As previously reported, IL-4 induced IgE and IgG4 secretion by B cells in PBMC preparations and B cells activated with EL4 cells and PMA. However, when B cells, either in PBMC preparations or purified and activated with EL4 cells and PMA, spontaneously secreted large quantities of immunoglobulin, IL-4 suppressed the immunoglobulin secretion of all isotypes. IL 4 also suppressed the IgE secretion by B cells from an atopic dermatitis patient. This suppressive effect was not reversed by adding IL-2 or interferon-gamma (IFN gamma) to the cultures. We also showed that TGF-beta suppressed the immunoglobulin secretion by purified B cells activated by EL4 cells and PMA. To investigate whether IL-4 or TGF-beta suppressed immunoglobulin secretion by in vivo 'switched' and isotype-committed B cells, sIgD- B cells were isolated, activated with EL4 cells and PMA and cultured with IL-4 or TGF-beta. Such activated B cells secreted large quantities of IgG1, IgG2, IgG3, IgA1, IgA2 and IgM, and IL-4 and TGF-beta suppressed all these isotypes by greater than 80%. The data demonstrated that IL-4 and TGF-beta suppress immunoglobulin secretion in vitro by in vivo isotype-committed sIgD- B cells, suggesting that these lymphokines may play a down-regulatory role on differentiated isotype-committed B cells in an isotype-unrestricted manner. The data also showed that IL-4 and TGF beta acted directly on isolated B cells. PMID- 1638771 TI - Interferon-gamma (IFN-gamma) and macrophage inflammatory proteins (MIP)-1 and -2 are involved in the regulation of the T cell-dependent chronic peritoneal neutrophilia of mice infected with mycobacteria. AB - In mycobacterial infections of mice there is a chronic, immune-mediated mobilization of neutrophils to the infectious site. In this study we evaluated the role played by cytokines in the chronic peritoneal neutrophilia which occurs in mice intraperitoneally infected with Mycobacterium bovis BCG or M. avium. Antibodies to IFN-gamma and to MIP-1 and -2 were effective in reducing peritoneal neutrophilia when given during the infection. Whereas the former antibody was only effective when given early, the latter two were effective when administered late in infection, suggesting the MIPs were direct mediators of neutrophil recruitment. Recombinant IFN-gamma given intraperitoneally induced the accumulation of neutrophils and primed the peritoneal cells for an enhanced recruitment of neutrophils. Our data show that chronic neutrophilia during mycobacterial infection is regulated by different cytokines acting at different stages and levels of neutrophil recruitment. PMID- 1638772 TI - In vitro activation of peripheral mononuclear cells by zinc in HIV-infected patients and healthy controls. AB - Zinc is a mitogen for peripheral blood mononuclear cells (PBMC). The optimal mitogenic concentration was found to be 0.05 mmol/l (327 micrograms/dl), four times higher than physiological serum levels. Maximal proliferation was observed after 6 days. Limited dilution technique revealed a frequency of zinc reactive cells of 1:3467 (median; range 1:1628-1:6235). Cord blood mononuclear cells from four of six healthy children could be stimulated to proliferate by zinc. A normal zinc-induced proliferative response could be demonstrated in all six HIV-infected patients in the Walter-Reed-stage I, in nine of 11 patients in Walter-Reed II and in only two of five patients in Walter-Reed III. In Walter-Reed IV to VI all eight patients showed a weak response to zinc (less than 50% of the healthy day control). Decreased zinc serum levels were found in 10 of 28 patients and in one of 16 controls. There was a significant correlation of a diminished zinc-induced proliferation with lower serum levels of zinc and a reduced proportion of CD4 helper cells in HIV-1-infected men. Because of a suppression of mitogenesis by high dose of zinc an excessive intake of zinc as used by some HIV-1-infected patients can presently not be recommended. The value of zinc-induced proliferation for monitoring HIV-infected patients has still to be established. PMID- 1638773 TI - Severe malaria in Gambian children is not due to lack of previous exposure to malaria. AB - The reasons why only a small proportion of African children infected with Plasmodium falciparum develop severe or fatal malaria are not known. One possible reason is that children who develop severe disease have had less previous exposure to malaria infection, and hence have less acquired immunity, than children who develop a mild clinical attack. To investigate this possibility we have measured titres of a wide range of anti-P. falciparum antibodies in plasma samples obtained from children with severe malaria, children with mild malaria and from children with other illnesses. Mean antibody levels in patients with malaria were higher than those in patients with other conditions but, with only one exception, there were no significant differences in antibody titres between cases of severe or mild malaria. A parasitized-erythrocyte agglutination assay was used to estimate the diversity of parasite isolates to which children had been exposed; plasma samples obtained from children with cerebral malaria recognized as many isolates as did samples obtained from children with mild disease. Our findings do not provide any support for the view that the development of severe malaria in a small proportion of African children infected with P. falciparum is due to lack of previous exposure to the infection. PMID- 1638774 TI - Disease association of antibodies to human and mycobacterial hsp70 and hsp60 stress proteins. AB - Structural homology between microbial and human stress proteins has been postulated to be a basis for autoimmunization in chronic inflammatory diseases. Therefore, we estimated by ELISA titration the antibody levels to mycobacterial (M) and human (H) recombinant hsp70 and M-hsp65 heat-shock proteins in sera of patients with Crohn's disease (n = 29), ulcerative colitis (n = 20) and nontuberculous mycobacterial disease of the lungs (n = 20). Antibodies to H hsp60, separated by two-dimensional gel electrophoresis, were tested in six sera of each group of patients. In Crohn's disease, antibody titres to the M-hsp65 antigen without detectable H-hsp60 binding were significantly elevated in 52% of the patients. In contrast titres to both M-hsp70 and H-hsp70 were demonstrable and correlated, but increased over control values only in four (14%) patients. The antibody pattern in ulcerative colitis was found to be quite different: anti H-hsp60 binding was demonstrable in most patients, although anti-M-hsp65 titres were not elevated. Furthermore, 25% of patients had significantly elevated titres to M-hsp70, but not to H-hsp70. In non-tuberculous mycobacterial pulmonary disease, about 50% of patients had elevated titres to both hsp65 and hsp71 mycobacterial antigens but not to the corresponding human proteins; patients with Mycobacterium xenopi infection had the highest titres in this group. These results demonstrate the existence of distinct disease-associated patterns in the human antibody response to stress protein antigens. However, these data are not sufficient to imply sensitization with mycobacteria in patients with inflammatory bowel diseases, since certain epitopes of heat-shock proteins are shared by several bacterial genera. PMID- 1638775 TI - IgA-containing immune complexes after challenge with food antigens in patients with IgA nephropathy. AB - The possibility that patients with IgA nephropathy (IgAN) might have abnormal IgA immune responses to immunogens commonly encountered at mucosal surfaces, resulting in the formation of circulating immune complexes (CIC), was examined. Since it is generally held that such increased IgA responses are characterized by detectable aberrancies in handling of IgA-containing CIC, IgAN patients and controls were given a large volume of bovine milk (after dietary deprivation of bovine antigens) and immune complex levels were measured over a period of 12 h. An assay based on binding of CIC containing C3 to solid-phase anti-C3 and subsequent development with isotype-specific antibody revealed no differences in responses of patients and controls with respect to IgG- and IgM-containing CIC. Although IgAN patients tended to have higher levels of IgA-containing CIC, there were no differences in response patterns when IgA CIC levels after ingestion of the milk stimulus were related to baseline levels. Polymorphonuclear leucocytes (PMNC), which bear surface receptors for IgA, were isolated from some subjects at the same times as the samples for CIC levels and examined by two-colour immunofluorescence for the coincident presence of IgA and milk antigens. In contrast to the data obtained in the CIC assays, these experiments revealed the simultaneous presence of IgA and two of three milk proteins in PMNC of IgAN patients but not controls. Follow-up experiments designed to assess more quantitatively the coincidental presence of IgA and milk antigens indicated no significant differences between patients and controls. However, milk proteins seemed to be more commonly associated with IgA in PMNC of IgAN patients, suggesting the presence of non-complement-fixing IgA/antigen CIC after mucosal challenge of some IgAN patients. PMID- 1638776 TI - How frequent is glomerulonephritis in diabetes mellitus type II? AB - A high frequency of glomerulonephritis (GN) in diabetics, or coexistence of GN with diabetic glomerulosclerosis, has been reported by previous authors, but the true prevalence of GN in diabetics remains to be established. In the Department of Pathology, Heidelberg, from 1.1.1987 to 31.12.1989 we examined all consecutive patients (89 male, 121 female, median age 74 years; 47-98) who came to autopsy with the diagnosis of "diabetes mellitus" to assess this issue in an unbiased sample. Five patients had known type I diabetes, the others type II diabetes or diabetes of unknown classification. In 61/159 patients, proteinuria had been present (no information in 51 patients) and in 99/169 patients renal failure, i.e. serum creatinine above 1.4 mg/dl (no information in 41 patients). Paraffin embedded kidney specimens from the upper pole of the left kidney were examined by immunohistochemistry (PAP technique; rabbit antihuman IgG; IgM; IgAab). 166/210 of the patients had glomerulosclerosis by light microscopy (129 diffuse, 37 nodular GS). Concomitant glomerulonephritis, i.e. typical mesangial IgA (and IgG) deposits, with mesangial enlargement by light microscopy were detected in only one case. Membranous GN was not found. These findings must be interpreted against the observation of mesangial immune deposits in 6 of 250 consecutive non-diabetic patients who had come to autopsy [Waldherr et al. 1989]. The findings show that an excessive prevalence of undiagnosed glomerulonephritis in our cohort of elderly type II diabetics was not to be found. PMID- 1638777 TI - Lovastatin in the treatment of hypercholesterolemia in nephrotic syndrome due to diabetic nephropathy stage IV-V. AB - The efficacy and safety of lovastatin, a drug for lowering hypercholesterolemia, have been evaluated in ten adult patients with insulin-dependent diabetes mellitus (IDDM) and nephrotic syndrome due to diabetic nephropathy stage IV or V of Mogensen. For the first 8 weeks the patients received only a sugar-free isocaloric diet of which fats supplied approximately 30% of the total caloric intake and with not more than 300 mg cholesterol daily. After this run-in period patients were treated with 20 mg lovastatin once daily for 12 weeks while receiving the same isocaloric diet as previously. Body weights and glycosylated hemoglobin concentrations (HbAlc) did not change significantly during this period. The baseline plasma cholesterol concentrations (mean +/- SD) decreased only by 2% (from 310 +/- 54 to 303 +/- 46 mg/dl) during the 8 weeks with low cholesterol diet and by 25% (from 303 +/- 46 to 228 +/- 38 mg/dl) during the 12 week period on lovastatin therapy (p less than 0.005). The mean concentrations of low-density lipoprotein (LDL-)-cholesterol decreased by 3% (from 218 +/- 53 to 211 +/- 52 mg/dl) during the diet period and by 35% (from 211 +/- 52 to 137 +/- 38 mg/dl) during the period with lovastatin therapy (p less than 0.001). Concentrations of high-density lipoprotein (HDL) cholesterol increased slightly (11%) during the therapy with lovastatin (NS). Baseline plasma triglycerides fell by 22% (from 188 +/- 97 to 146 +/- 59 mg/dl) during the period with fat restriction (p less than 0.05) and by 13% (from 146 +/- 59 to 127 +/- 54 mg/dl) during the period of lovastatin therapy (NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1638778 TI - Mesangial anionic sites are decreased in human focal glomerular sclerosis. AB - We studied the mesangial anionic sites in two patients with focal glomerular sclerosis (FGS), using polyethyleneimine as a cationic probe. The mesangial negative charge in the FGS patients was less than that in three control patients. The decrease in negative charge in FGS concerned the central, paramesangial, as well as the subendothelial region of the mesangium; the decrease was most pronounced in the central region. It is proposed that loss of mesangial negative charge may have pathogenic significance in FGS. PMID- 1638779 TI - Two distinct types of crescentic glomerulonephritis. AB - For a characterization of the clinical course of crescentic glomerulonephritis (Cres. GN), reciprocals of serum creatinine concentration (1/Cr) as a function of time were studied in 24 patients. The patients fulfilled the following criteria; 1) crescents were observed in more than 50% of glomeruli, and 2) the increment of serum creatinine could be determined sequentially on three or more occasions in the phase of progression of renal impairment. In all patients 1/Cr declined linearly with time with correlation coefficients between 0.881 and 0.993. According to the slope, the patients were divided into two groups; an acute group (13 patients) with slopes of -1.0 x 10(-2) dl/mg/day or more steep, i.e. with increments of serum creatinine from 1.0 to 10.0 mg/dl within 90 days, and a subacute group (11 patients) with less steep slopes. Histologically, there was no difference in the percentage of glomeruli with crescents between the two groups. However, in the acute group a negative correlation was found between the period from onset to histological examination and the percentage of glomeruli with cellular crescents in all glomeruli with various crescents (r = -0.872, p less than 0.001), while in the subacute group the percentage was nearly constant regardless of the time of histological examination. These mean drastic but transient activation of the disease in the former in spite of a persistence of indolent activity in the latter. Clinically, in the acute group an improvement of serum creatinine was observed in 8 (61.5%) vs. only 2 (18.2%) in the subacute group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1638780 TI - Nephrotic-range proteinuria associated with right atrial myxoma. AB - A case of right atrial myxoma presenting with right heart failure and proteinuria is described. Proteinuria was variable and this corresponded with the degree of systemic venous congestion. On one occasion the proteinuria was within the nephrotic range. There was no evidence of intrinsic renal pathology. The right heart failure and proteinuria resolved after tumour removal, suggesting that the etiology of urinary protein loss was a reversible increase in glomerular permeability. PMID- 1638781 TI - Acquired renal cystic disease in HD: a study of 82 nephrectomies in young patients. AB - In order to study the development of acquired renal cystic disease (ARCD) and its potential complications, we studied, macro- and microscopically, 82 surgical specimens of nephrectomy carried out on young patients with chronic renal failure previous to renal transplantation. Statistical correlation of pathological findings with age, sex and time on hemodialysis (HD) have been done. There were 72 cases of ARCD (87.8%). It was statistically correlated with male sex (p less than 0.02) and prolonged time on HD (p less than 0.001) as has been previously reported. Hyperplasia of the cystic epithelium was found in 42 cases (52%), with 18 (22%) showing marked papillary proliferation. Also, there were 22 cases (27%) with renal adenomas. This incidence of hyperplastic and neoplastic proliferations, more than would be common in such a young population (males: 33.5 +/- 9.3 years; females: 35.4 +/- 11.7 years), suggests the potential of patients affected by ARCD to develop neoplasms. Thus, we consider that these patients must be checked periodically to detect possible malignant neoplasms. PMID- 1638782 TI - Serum creatinine concentration at the onset of uremia: higher levels in black males. AB - We compared serum creatinine and blood urea nitrogen concentrations, estimated creatinine clearances and frequency of uremic symptoms at the start of chronic hemodialysis in all 20 black and 179 white males treated between 1969 and 1983. Serum creatinine concentrations were significantly higher in black males (16.5 +/ 5.9 mg/dl) than in white males (11.7 +/- 4.7 mg/dl; p = 0.016). There were no significant differences in blood urea nitrogen concentration, estimated creatinine clearance and frequency of uremic symptoms between the two groups. Blood urea nitrogen to serum creatinine ratios were lower in black males, (7.3 +/ 1.9) than in white males (11.4 +/- 3.8; p = 0.0001), and only one black male had a ratio greater than 10 compared to 60% of whites. We concluded that black males tend to have higher serum creatinine concentrations than white males at the onset of uremic symptoms, and that higher striated muscle creatinine production in black males and not lower renal function may be the cause. PMID- 1638783 TI - Blood pressure reduction during hemodialysis correlates to intradialytic changes in plasma volume. AB - Blood pressure alterations during hemodialysis were related to changes in body fluid in 14 patients with chronic renal failure. Changes in plasma volume (PV) and extracellular volume (ECV) were calculated from determinations of fluid volumes before and after hemodialysis, using 125I-albumin and 51Cr EDTA respectively. Reduction in body water was estimated from body weight changes. Weight loss was 3.3 +/- 0.3 kg (range 1.8-6.0 kg). The relative reduction of fluid was greater in the ECV, 21.6 +/- 3.2%, compared to plasma volume, 6.9 +/- 1.8%. The reduction in systolic blood pressure was related to both absolute (r = 0.66, p less than 0.05) and relative PV reduction (r = 0.72, p less than 0.02). There was no correlation between blood pressure reduction and weight loss or ECV changes. Only minor alterations were found in diastolic blood pressure. Plasma volume maintenance relates to blood pressure changes. Plasma volume monitoring could be useful for improving intradialytic hemodynamic control. PMID- 1638784 TI - Progression of membranous glomerulopathy during cyclosporin A. PMID- 1638785 TI - Symposium: The Future of Academic Medicine in Canada. Quebec City, Quebec, September 1991. PMID- 1638786 TI - The future of academic medicine within the health care system in Canada. PMID- 1638787 TI - How to attract candidates to academic medicine. AB - The current trends in career choices of our graduates, the changing expectations of the health care sector, the increasing complexity of the health care delivery system, and the changing demographics of our health care providers suggest that Canada may be facing an undersupply of academic physicians for the future needs of academic medicine unless we, collectively, address the issue and provide some solutions. It is equally clear that there is no single or simple solution to the problem of attracting candidates to academic medicine. Based on the best available information and projections, I would suggest that the following might be part of the solution: 1. Medical schools need to articulate their missions and goals, especially with respect to the desired educational outcomes. In doing so, it is critical that they not become 'carbon copies' of each other, but that each builds on individual strengths, recognizing the value of diversity of missions. The 16 medical schools should cooperate and formulate complementary objectives to meet the needs of society. 2. Planning of physician resources must be broad and nationally based, and must include the needs of academic medicine. In defining the nature and numbers of clinician-scientists required, the best available data must be sought - not just for the current situation, but for trends that have created the present situation. This must also be coupled to realistic projections of future needs of the health care delivery system and of academic research and teaching needs. 3. Educational programs at all levels (undergraduate, postgraduate, and continuing medical education) must be structured to ensure that they do not inadvertently discourage potential academics from their career goals. They must actively seek and encourage the talented individual destined for an academic career, and provide a career pathway that facilitates achievement of those goals and eliminates the barriers and restrictions that preclude the attainment of those career goals. Medical schools, accrediting groups, specialty societies, colleges, and licensing bodies must participate in a joint dialogue to meet these goals. The special needs of women must be addressed to enhance their participation in the academic enterprise. 4. Governments, universities, and funding agencies must begin to address the special needs of the research and teaching community, to provide security and stability that translates into a realistic career goal worthy of the commitment and dedication of our scientists, and to make academic medicine an attractive option for our bright and talented individuals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1638788 TI - How to attract candidates to academic medicine: the role of postsecondary institutions. PMID- 1638789 TI - Restructuring undergraduate medical curriculum: an opportunity to attract students to academic medicine. PMID- 1638790 TI - Research education in residency programs. PMID- 1638791 TI - Results of recent initiatives such as the MD/PhD program in the training of clinician-scientists. PMID- 1638792 TI - The training pathway of clinician-scientists and teachers. PMID- 1638793 TI - The training pathway of clinician-scientists and teachers: the view from the university. PMID- 1638794 TI - The responsibility of department chairmen and deans to ensure training of clinician-scientists. PMID- 1638795 TI - Is there a fast track for the training pathway of clinician-scientists and teachers? PMID- 1638796 TI - The training pathway of clinician-scientists: the view from the Royal College. PMID- 1638797 TI - [The role of research centers and institutes for biomedical contemporary research]. PMID- 1638798 TI - Cost-effectiveness of academic medicine. PMID- 1638799 TI - Nurturing the young academician. AB - The young academic physician requires a well prepared and supportive environment if the trials and uncertainties associated with the early years of an academic appointment are to be successfully overcome. It is the responsibility of the appropriate university and hospital authorities to create this environment and to ensure that the appointed academician is appropriately supported within it. Of particular importance is the development by all parties of an understanding of the job description of the new faculty member and of the time and income arrangements that must be made if this description is to be fulfilled. PMID- 1638800 TI - The young investigator in Canada. PMID- 1638801 TI - Salary structure, promotion, and tenure policies in nurturing the young academician. AB - With respect to salary structure, promotion, and tenure for academic clinical faculty, and based on the issues I have described, we must consider the following five priorities: 1. To provide salary support which is appropriate for responsibilities in teaching, research, and clinical administration, and not dependent on clinical earnings, 2. To maintain flexible salary arrangements which may include a component of clinical fee-for-service earnings, and partial salary support for defined clinical teaching or administration, 3. To design a more integrated management system for these new funding arrangements which brings together medical schools and teaching hospitals and is accountable to the appropriate government agencies. 4. To improve performance review and promotion procedures, based on agreed job descriptions and recognizing the importance of teaching, research, clinical administration, and service, and 5. To review critically the role of tenure for academic clinicians and examine alternatives such as renewable term appointments There is a growing momentum to address these issues and priorities among all of those involved. This will be critical in the continued career development of Canadian academic physicians. PMID- 1638802 TI - Nurturing the young academician: the role of funding agencies. PMID- 1638803 TI - Nurturing the young academician: view from the Fonds de la Recherche en Sante du Quebec (Medical Research Council of Quebec). PMID- 1638804 TI - Career development and the training of clinician-scientists. PMID- 1638805 TI - The role of the pharmaceutical industry in nurturing the young academician. PMID- 1638806 TI - Nurturing the young academician: the role of funding agencies and industry. PMID- 1638807 TI - The influence of governmental decision-making on academic medicine: Part II. PMID- 1638808 TI - Government decision-making and academic medicine. PMID- 1638809 TI - Influence of immigration and licensing bodies on academic medicine. PMID- 1638810 TI - Lobbying for research and academic medicine. PMID- 1638811 TI - The academic physician as spokesman and salesman. PMID- 1638813 TI - Operative hysteroscopy. PMID- 1638812 TI - The influence of governmental decision-making on academic medicine: view from the government of Quebec. PMID- 1638814 TI - Instruments and video cameras for operative hysteroscopy. PMID- 1638815 TI - Operative hysteroscopy for infertility. PMID- 1638816 TI - Hysteroscopic laser surgery. PMID- 1638817 TI - Hysteroscopic surgery using the resectoscope: myomas, ablation, septae & synechiae. Does pre-operative medication help? PMID- 1638818 TI - Complications of operative hysteroscopy: how safe is it? PMID- 1638819 TI - Electricity inside the uterus. AB - Although electrosurgery has been employed for decades, few surgeons have received formal training in its proper use. The erroneous belief that electrosurgery techniques increase scar formation or impair healing processes led surgeons to use other methods to deliver energy to the living cell. At the cellular level, 1 watt is 1 watt. Knowing how to calculate and administer this amount of energy is the challenge. Laser technology fostered the development of improved electrogenerators and accessories that are easier to understand and control. The use of digital reader boards, displayed in watts rather than an arbitrary dial setting, is one example. A good electrosurgical system, with proper accessory electrodes, costs only 10% of the price of the average laser. For hysteroscopic resectoscopy procedures, a thorough knowledge and appreciation of the physics of electrosurgery is a basic requirement. In the future, I hope the power density and wattage delivered at the electrode tip will be displayed easily for surgeons using the resectoscope. One day, we may have a "laser-electrode" system to meet all our needs. PMID- 1638820 TI - Office hysteroscopy. AB - Most operative office surgery can be done easily. If, midway through a procedure in the office, the operator finds that a myoma is too large or deep to resect safely in the office, the procedure can be terminated and rescheduled for the operating room. Polyps, retained products, and the lost intrauterine device all can be treated similarly. With the proper equipment and patient selection, the well-trained hysteroscopist can do extensive operative hysteroscopy in the office. With experience, the hysteroscopist can do diagnostic and operative hysteroscopy at the same time, resulting in a substantial savings of both cost and time for the patient and the physician. The future of office hysteroscopy may include endometrial ablation and transcervical sterilization, in addition to the procedures described in this chapter. Diagnostic hysteroscopy is becoming a standard part of office gynecology. With continued training, operative hysteroscopy will move into the realm of office gynecology at the same level as diagnostic hysteroscopy. PMID- 1638821 TI - Hysteroscopic sterilization. PMID- 1638822 TI - Tubal surgery from the inside out: falloposcopy and balloon tuboplasty. PMID- 1638823 TI - Hypertension in pregnancy. PMID- 1638824 TI - Pathogenesis of preeclampsia: a hypothesis. PMID- 1638825 TI - Abnormal hemostasis and coagulopathy in preeclampsia and eclampsia. AB - Preeclampsia and eclampsia appear to be a state of increased coagulopathy as evidenced by an increase in fibrin formation, activation of the fibrinolytic system, platelet activation and a decrease in platelet count. Routine tests used to assess decompensated disseminated intravascular coagulopathy are of limited value in the preeclamptic and eclamptic population. More sophisticated tests such as determinations of antithrombin III, thrombin-antithrombin III complex, D dimer, factor VIII antigen/activity ratio, and beta-thromboglobulin, however, show a compensated coagulopathy in the preeclamptic patient. These hemostatic changes, probably the result of endothelial damage, are implicated in the pathogenesis of this disease. A better understanding about the abnormalities of hemostasis and coagulation in the preeclamptic and eclamptic patient may allow the clinician to provide improved management and possibly peripartum therapy. PMID- 1638826 TI - The prediction of preeclampsia. PMID- 1638827 TI - Prophylaxis of eclamptic seizures: current controversies. AB - Treatment of this pathophysiologically poorly understood disease is controversial. Despite this uncertainty, the goals of management of the patient with preeclampsia and eclampsia are diagnosis, stabilization, and delivery of the baby. Stabilization refers to both mother and fetus and should include the prevention of eclampsia or the recurrence of eclamptic seizures. There are empiric data supporting the use of magnesium sulfate for the management of preeclampsia and eclampsia in North America, but there are few data to support its efficacy as a classic anticonvulsant. Until controlled trials are completed, we suggest that magnesium sulfate continue to be used in preeclampsia, with the addition of established anticonvulsant medications when eclampsia occurs. Data on established antiepileptic drugs such as diazepam and phenytoin support their use in treating patients with eclamptic seizures. As stated in an earlier review, "in treating preeclampsia, magnesium sulfate therapy may have a role and may moderate factors leading to eclampsia. Whether magnesium sulfate therapy may have some as yet unproved effect on epileptogenic foci or seizure propagation is not the important issue for the physician caring for the eclamptic patient. Until adequately designed therapeutic trials are available, it is our opinion that treatment should be based on the use of anticonvulsant drugs of established efficacy in seizure control and prophylaxis (p. 1363)." PMID- 1638828 TI - The maternal hemodynamics of preeclampsia. PMID- 1638829 TI - Surveillance of the pregnant hypertensive patient with Doppler flow velocimetry. PMID- 1638830 TI - Portable blood pressure monitoring for borderline or mild hypertension during pregnancy. AB - Several advantages are apparent in the use of self-monitored or automatic ambulatory blood pressure monitoring by pregnant patients who appear to have borderline or mild hypertension. Home recordings, combined with conventional office measurements, can give a more accurate picture of the patient's dynamic blood pressure. Blood pressures are often lower outside the physician's office, probably because of the patient's increased awareness and decreased anxiety in other settings. When blood pressures are normal at home, the patient may be able to avoid antihypertensive therapy, antepartum hospitalization, and intervention during her pregnancy. Monitoring at home or work also provides a more thorough screening for preeclampsia, especially with patients who have chronic hypertension or other predisposing conditions. PMID- 1638831 TI - Acute life-threatening emergencies in preeclampsia--eclampsia. AB - Severe dysfunction of the pulmonary, renal, hepatic, and central nervous systems as a consequence of preeclampsia--eclampsia warrant aggressive multidisciplinary management and treatment. Preventive therapy, when possible or early recognition and therapy are clearly associated with improved maternal and neonatal outcome. Should cardiopulmonary arrest occur as a function of the disease process or management, then perimortem cesarean delivery initiated within 4 minutes of maternal cardiac arrest is associated with the highest rates of maternal and neonatal survival. PMID- 1638832 TI - Pathophysiology and anesthetic implications in preeclampsia. PMID- 1638833 TI - Management and counseling of patients with preeclampsia remote from term. PMID- 1638834 TI - Hepatobiliary scintigraphy in pediatric liver transplant recipients. AB - The clinical usefulness of hepatobiliary scintigraphy was evaluated in pediatric liver transplant recipients. One hundred fifteen hepatobiliary scintigraphic studies were performed in 30 patients who received 22 whole liver and 16 segmental grafts. Parameters that were useful in predicting an adverse outcome were failure to visualize excreted radiopharmaceutical at or beyond the biliary anastomosis on a study performed within 24 hours after transplant, and persistent or increasing delay in the time of visualization of excreted radiopharmaceutical. Abnormalities of liver uptake and excretion were seen in rejection, but they were also seen in patients who remained well without rejection or parenchymal disease. Significant biliary leaks were identified in the three cases in which they were known to be present. In liver transplant recipients, hepatobiliary imaging is useful in predicting graft survival and identifying biliary leaks. PMID- 1638835 TI - Rapid determination of glomerular filtration rate in infants using Tc-99m DTPA. AB - Glomerular filtration rate obtained by using Tc-99m DTPA was compared with that obtained from Schwartz's formula using serum creatinine and length in 21 infants (age range, 3 to 348 days). The GFR (mean +/- SD) obtained by Tc-99m DTPA was 76 +/- 37 ml/min per 1.73m2 and by the Schwartz formula was 83 +/- 49 ml/min per 1.73m2. GFR by Tc-99m DTPA method overestimated GFR by 3.6% compared to the Schwartz method. The imaging technique and the advantages are discussed. PMID- 1638836 TI - Panostotic fibrous dysplasia. A new craniotubular dysplasia. AB - The authors describe the radiographic-scintigraphic features of an unusual craniotubular dysplasia characterized by diffuse osteopenia with bone expansion and a "ground glass" appearance, markedly increased skeletal turnover, myelofibrosis, hypophosphatemia, and pigmented "coast-of-Maine" patches. This syndrome, termed panostotic fibrous dysplasia, is distinct from previously reported disorders. PMID- 1638837 TI - Melorheostosis on three-phase bone scintigraphy. Case report. AB - Melorheostosis is a benign sclerosing bone dysplasia with a very unusual and characteristic roentgenographic appearance. Its scintigraphic appearance also is characteristic, with asymmetric cortical activity that may cross joints to involve contiguous bones. The authors report the appearance of melorheostosis on angiogram and blood pool phases of three-phase bone scintigraphy. PMID- 1638838 TI - The relationship between thallium uptake, blood flow, and blood pool activity in bone and soft tissue tumors. AB - Twenty patients with known primary untreated and recurrent bone and soft tissue tumors underwent thallium imaging and three-phase bone imaging in the same session. The ratio of thallium uptake in the tumor tissue to the contralateral normal tissue areas was compared with the same ratio for phase 1 (blood flow or arterial phase), phase 2 (blood pool), and phase 3 (delayed medroxy diphosphonate, MDP, uptake). There was poor correlation between Tl uptake and phases 1 and 3 of the bone scan ratios; r = 0.37 and 0.46; P = 0.097 and 0.047, respectively. The thallium uptake ratios correlated well with blood pool ratios (phase 2) (r = 0.84 and P less than 0.01). In contrast to uptake into normal muscle, Tl-201 uptake into tumor is not highly dependent on blood flow alone and other factors predominate in determining its magnitude. PMID- 1638839 TI - Metastatic malignant struma ovarii. Two case reports. AB - Struma ovarii is an ovarian germ cell tumor consisting mainly of thyroid tissue. Five percent of struma ovarii are malignant, and of these only five percent metastasize. The rarity of this disease has resulted in difficulty in agreeing on treatment regimes and in limited imaging experience. The authors report two cases and highlight the imaging and monitoring difficulties encountered in their management. The authors conclude that I-131 has a role to play both therapeutically and in monitoring these patients, but that biochemical testing is a more reliable indicator of disease status. PMID- 1638840 TI - The 'hot halo' sign. Pyogenic pericarditis on In-111 leukocyte scintigraphy. AB - The authors report a patient with diffuse pyogenic pericarditis and focal myoendocarditis initially detected using In-111 WBC scintigraphy. The patient was in septic shock after hemodialysis for the treatment of chronic renal failure. This was preceded by clinical signs and symptoms of pericarditis thought to be viral in nature. Initial investigations found no septic focus, and the patient was referred for In-111 WBC scintigraphy. This revealed a striking "halo" of increased activity around the heart, strongly suggesting bacterial pericarditis. A subsequent pericardiocentesis yielded 400 ml of purulent material, confirming the diagnosis. PMID- 1638841 TI - Acetazolamide effect on vascular response in areas with diaschisis as measured by Tc-99m HMPAO brain SPECT. AB - The effects of acetazolamide (Diamox) on vascular response were investigated in areas with intrahemispheric thalamic diaschisis and crossed cerebellar diaschisis using consecutive Tc-99m HMPAO brain SPECT studies before and after Diamox administration. All six patients with thalamic diaschisis and five of eight patients with crossed cerebellar diaschisis at baseline showed significantly augmented perfusion after Diamox administration in the affected thalamus and cerebellum compared with that in the contralateral unaffected areas. These results suggest more dilatation of the arterioles in areas with diaschisis after Diamox administration than in areas without diaschisis. Diamox may produce relative luxury perfusion in areas with diaschisis. PMID- 1638842 TI - Detection of pseudomembranous colitis by Tc-99m HMPAO labeled WBC and Ga-67 citrate. PMID- 1638843 TI - Demonstration of a lymphocele by interstitial immunolymphoscintigraphy. PMID- 1638844 TI - Diagnostic significance of dental history in the clinical evaluation of patients with thyroid carcinoma. Periodontal surgery mimicking a metastasis on I-131 whole body survey. PMID- 1638845 TI - Visualization of a popliteal pseudoaneurysm by radionuclide imaging. PMID- 1638847 TI - Free-floating thrombus identified by radionuclide venogram. PMID- 1638846 TI - Infected knee prosthesis. Visualization of the fistulous tract by Tc-99m HMPAO leukocyte scintigraphy. PMID- 1638848 TI - Renal scintigraphy of en bloc transplantation of pediatric kidneys. PMID- 1638849 TI - Heterotopic calcification of the popliteal fossae. PMID- 1638850 TI - Scintigraphic diagnosis of costal periostitis in actinomycosis. PMID- 1638851 TI - 'Bull's eye' appearance of hyperostosis frontalis interna. PMID- 1638852 TI - [New horizons of the scientific thought. The use of systems science and cybernetics in medicine]. PMID- 1638853 TI - [Correction by physiotherapy of immune disorders in high-grade athletes]. AB - It is well known that during intense training and competitions athletes show a remarkable reduction of their immunological responses. As a matter of fact, during these periods athletes very frequently (five to ten times more than average) fall ill. In order to correct this situation, in the USSR immunomodulator drugs are used together with high frequency electromagnetic waves which are applied on the body surface corresponding to the adrenal glands. In this way body desensitisation is accelerated. One hundred high-level athletes received an application of electromagnetic waves on the body surface corresponding to the thyroid gland and thymus, so as to lower glucocorticoid activity and activate lymphoid tissue. Indices of immunologic reactivity and hormonal levels after electromagnetic treatment were measured in all athletes. PMID- 1638854 TI - [Behavior of the lithium excretion fraction in hypertensive patients during variations of sodium intake]. AB - Fractional excretion of lithium (FeLi) is a marker of proximal tubular sodium reabsorption. During different sodium intakes (normal = 120 mEq/day, low = 40 mEq/day and high = 240 mEq/day) fractional lithium excretion was evaluated in essential hypertensive patients (n. 19) and control subjects (n. 5). Our data showed that FeLi was higher in hypertensives than in controls. Dividing hypertensives on the basis of blood-pressure sensitivity, salt resistant patients showed lower FeLi levels as compared to salt sensitive ones. Our findings indicate that proximal tubular sodium reabsorption is decreased in essential hypertension; this behavior is particularly evident in salt sensitive patients, suggesting that factors affecting proximal tubular function are activated in these patients in order to reduce the impairment of renal excretory capability. PMID- 1638855 TI - [Ultrasonography and ultrasound-guided biopsy in lymphomas]. AB - The authors have reviewed the literature on imaging techniques for the diagnosis of lymphoma. Lymphography, axial computerized tomography (CT) and echotomography have been compared as to their sensitivity and specificity. Lymphography allows diagnosis of the disease even in lymph nodes of less than 0.5 cm diameter, but this technique cannot be applied to all lymphatic station. Echotomography and CT are equivalent as to the accuracy of diagnosis and are both helpful for guided needle biopsy. In view of its low cost, echotomography is considered by most workers the first-line approach to the evaluation of lymphoma patients. In spite of its advantages over other methods, echotomography must, nevertheless, be integrated by CT, lymphography, and nuclear magnetic resonance. PMID- 1638856 TI - [Psycho-functional changes in attention and learning under the action of L acetylcarnitine in 17 young subjects. A pilot study of its use in mental deterioration]. AB - The aim of the study was the investigation of the ability of L-acetylcarnitine (Acn; 1.5 g daily oral route for 1 month) to enhance some performances requiring a high level of attention and reflex velocity. The sample includes 17 healthy subjects, 8 males and 9 females, 22 to 27 years old; 10 of the subjects practice sports at agonistic level, while 7 have a sedentary life style. Reflexes have been measured, baseline and after 17 and 30 days of Acn administration, through a purposely constructed reflex-meter able to determine the latency (csec) of the reaction to an auditory stimulus. The ability as well as the time of learning was determined, before and after treatment, as the time and the number of errors to get out of the maze of a videogame (the test was also carried out by an untreated control group). Acn seems to induce an enhancement of reflex velocity, with complete annulment of the difference between the dominant and the opposite hand, as well as a significant reduction (3 to 4 times superior to controls) of both the errors and the time with the maze test. PMID- 1638857 TI - [Drug-induced changes in the teeth and mouth. II]. AB - As in the previous paper the unwanted effects of drugs or chemicals in the orofacial region are described. The authors take into consideration alterations such as gingival hyperplasia and hypertrophy, discoloration of the oral mucosa and teeth, oral ulceration and stomatitis, cervical lymphadenopathy, drug induced blood dyscrasias, bleeding caused by aspirin and other drugs, and cleft lip and cleft palate. PMID- 1638858 TI - Ten-year review of overall survival rates for stage I cutaneous melanoma in 3,009 residents of Connecticut. PMID- 1638859 TI - Yersinia enterocolitica contamination of blood products. Connecticut State Medical Society Committee on Organ and Tissue Transfers. PMID- 1638860 TI - Renal failure associated with lymphoma in acquired immunodeficiency syndrome. AB - An unusual case of acute renal failure associated with lymphoma and acquired immunodeficiency syndrome (AIDS) is described. There was an impressive response to chemotherapy and parallel improvement in renal function. The rare occurrence of lymphoma-related renal failure in AIDS patients is presented as well as a review of the different ways AIDS and lymphoma can impair renal function. PMID- 1638861 TI - 7 practice-management tips to increase productivity. PMID- 1638862 TI - Leverett Hubbard, M.D. A biographical memoir of the first president of the Connecticut State Medical Society, 1942. PMID- 1638863 TI - Connecticut's second medical school. PMID- 1638865 TI - Mutual interest or self interest. PMID- 1638864 TI - Reconsidering confidentiality. PMID- 1638866 TI - Pluripotent stem cells and early B lymphocyte precursors in mice. PMID- 1638867 TI - Evaluating functional abilities of primitive hematopoietic stem cell populations. PMID- 1638868 TI - The stem cell compartment: assays and negative regulators. PMID- 1638869 TI - Marrow transplantation. PMID- 1638870 TI - Careful maintenance of undifferentiated mouse embryonic stem cells is necessary for their capacity to differentiate to hematopoietic lineages in vitro. PMID- 1638871 TI - The pre-spleen colony-forming unit assay: measurement of spleen colony-forming unit regeneration. PMID- 1638872 TI - Spleen colony-forming unit: a myeloid stem cell. PMID- 1638873 TI - Being old. A subjective description of becoming and being old. AB - Every individual is unique. The history and the life of a person is unique. This is a description by an old general practitioner of the experience of becoming and being old. PMID- 1638874 TI - The elderly in Denmark. PMID- 1638875 TI - Images of aging--over the last 100 years. AB - Discussions on care of the elderly today often lack definitions of various issues and concepts relating to the elderly in question and their needs. One problem is the tendency to categorise the elderly in general as one homogeneous group of frail individuals. Another is an increasing tendency to paint a posy picture of the third age, overlooking the problems of "the fourth age". The categorisation of "the elderly" dates back 100 years in history, when the first political initiatives on pension policy were taken. Denmark was the first country to introduce such legislation, with old age (over 60) as the basic criterion. However, the basis for drawing a vertical line at the age of 60 was a series of findings by German and French scholars of medicine and statistics on age-related decline in various functions. The development of geriatric medicine occurred rather late in Denmark, probably because of a relatively high level of quality and capacity of social institutions and other services for the elderly. Thus, longterm care for old people was not a major issue in the health care system until recent decades. Today, the new images of aging are not limited to visualisation of old people in "the third age". Nursing homes are changed to individual flats and provision of 24-hour home care services is available. This development requires coordinated education, training, and management of staff. A better knowledge of the changing images of aging in history is an important element of staff development. PMID- 1638876 TI - The Glostrup Population Studies, 1964-1992. AB - The Glostrup Population Studies, 1964-92, comprise descriptive and analytical, clinical epidemiological studies. Since 1964, different birth cohorts have been examined. More than 20,000 persons, randomly selected from the background population of 300,000 inhabitants (Copenhagen County), have been invited to participate. The project started in 1964 with a survey of the 1914 population on risk factors for coronary heart disease. As the 1914 population has been followed and new cohorts added, a time-sequential design, suited for studies of aging, has been constructed. The staff has been kept in the unit for up to 28 years. Doctoral candidates in medical science and Ph.D candidates have defended their analyses of Glostrup data in several fields and continue to belong to the group of representatives, supporting the board of leaders. The head of Medical Department C serves as chairman, thus maintaining a close connection with clinical medicine. PMID- 1638877 TI - 85-year-olds in Denmark. The socio-psychological conditions and general health and disorders in a representative group of 85-year-old Danes. AB - A population of persons born in 1897 and resident in Glostrup and eight surrounding municipalities was investigated when these persons were 70, 80 and 85 years old. Some of the results are mentioned from the cross-sectional, epidemiological survey on the socio-psychological conditions and general health and disorders in this representative population which includes almost 2% of the Danish 85-year-olds. The examination programme was extensive, and of data rather comprehensive. The aim of this article is to make known some of the information, observations and results of several tests performed, including 56 different laboratory tests and nutritional analyses. It is worth mentioning that about three fourths of the 85-year-olds were self-reliant and contended with their actual life and lifestyle. Nevertheless suggestions or recommendations for interventions were given to 85% of the participants as well as the general practitioners. The data have already formed the basis of several frames of references. PMID- 1638878 TI - To grow old. From a socio-medical epidemiological intervention study among old citizens of Copenhagen. AB - A cross-sectional, epidemiological, sociomedical survey, followed by intervention, was conducted with the participation of 585 men and women in the 75, 80 and 85 year-old age groups living in the city of Copenhagen. The main objectives of the study were to describe the health and social conditions of the elderly people, to register the physical and social unmet needs and then intervene to relieve these needs, to assess the effect of such an intervention through a follow-up study, and to demonstrate possible risk factors. Age, marital status, recent hospitalisation were shown to be connected with the functional condition. The quality of life study showed that health, functional ability to stay independent, and housing conditions are most important factors when growing old. The socio-medical intervention did not show any effect with regard to mortality, hospitalisation, institutionalisation, subjective health and economy, loneliness, quality of life and functional ability. The most striking risk markers in relation to death were: low systolic blood pressure among women, subjective poor health, low score on the ladder-scale used to quantify quality of life, and impaired functional capacity in nine out of ten partial functions. All together, it is concluded that if we want to improve the living conditions of the elderly we should reserve the efforts for old people at risk and enable as many as possible to stay independent. PMID- 1638879 TI - Attitudes to aging and old age. AB - In the 1980s a marked shift in the attitude to aging and the elderly made itself felt. In the beginning of the decade the commission for the elderly proposed a policy based on continuity and self-determination and with a starting point in the resources of the elderly. This attitude has come through in the political activities on different levels and is also reflected in the DaneAge Future study, where three cohorts--40-44 years, 50-54 years, 60-64 years--show an optimistic and self-confident attitude to their own old age. PMID- 1638880 TI - Ten years after the Commission on Aging--ideas and results. AB - During the years 1979-82, the Commission on Aging scrutinised public measures relating to the elderly and recommended adherence to the principles of continuity, self determination and use of own resources in future aging policy. A central point in the Commission's perception of aging was that a number of functional impairments previously considered exclusively a reflection of the biological aging processes were now seen as equally induced by loss of roles and social functions. The renewal of structures and development work carried out throughout the country are based on these principles, integrating social and psychological considerations. Work is also based on the Report on the Public Sector (1988) which recommends enhancement of social networks and self-help capabilities of the old as well as new forms of cooperation between the public sector and citizens. Self determination and self control have become new key words in current aging policy. The new policy is not only induced by financial pressure on the public sector, but equally to the realisation that many social tasks are best solved in cooperation with individuals. The renewal of aging policy is also adapted to the new generations of elderly people, who want freer lifestyles and more options than many of the old have today. They will very likely be more mobile and make more demands for their life. They have been accustomed to creating networks and cross-contacts, as their jobs and interests have required it, and their health and financial circumstances will frequently be better than those of the elderly generation today.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1638881 TI - The situation of the elderly in Denmark. AB - In this paper, basic socio-economic and demographic data about the elderly are presented. Since the younger elderly are more active and have better health than previous generations and since the older elderly comprise the group likely to make most demands on society, the paper concentrates mainly on those aged 75 and over. The demography of the elderly is considered by way of introduction, followed by more specific topics of particular interest for the group in question, such as finance, household composition, institutions and service, health and family structure. In conclusion, the inter-action between the public sector, the private sector, the independent sector (volunteers) and the family (social) network is considered in relation to ensuring acceptable quality of life for elderly persons in Denmark. PMID- 1638882 TI - The development in local authority services for the elderly. AB - Services for elderly people in Denmark are managed by the local authorities. Expenses for the elderly account for 65% of the local authority expenses in the social sector. During recent years, the Danish government has made increasing demands on the local authorities to limit public resources. The number of elderly people is still increasing, particularly within the oldest age groups; an increasing number of elderly suffer from senile dementia, and sick elderly people remain in their own homes, due largely to changes in discharge practice by the public hospitals. Therefore, the local authorities have tried new ways and have modified the level of service for the elderly within unchanged financial limits. In order to maintain a good level of service, it has become necessary to increase the efficiency and flexibility in the use of resources and to transfer a number of tasks to both the staff and the elderly themselves. The article gives a broad survey of the Danish services for the elderly and the local authorities' experience with the restructuring. PMID- 1638883 TI - The role of private organisations in welfare work. The historical perspective. AB - The Danish welfare measures originated in private initiatives. From the end of the last century, welfare activities have developed through private relief organisations and with support from the State, local governments, and counties. Since the 1960s, many institutions which had been built up by private relief organisations were actually taken over by local governments or counties. By way of illustration, the development of EGV DaneCare (the Danish Association for the Care of the Elderly), from its origin as a voluntary relief organisation based on voluntary work and collected funds, is described. From 1910, EGV was the pioneer within the field of, for example, old people's homes, winter shelters, and holidays in the country for elderly people. In the 1960s, EGV became a professional service organisation which assisted the local governments in developing a wide range of variegated offers within the work for elderly people. Assistance offered to the local governments became the organisation's principal project up to the 1980s. The population's confidence in the ability of the public authorities to cope with the social tasks was at the time undermined by increasing scepticism. That was why EGV founded the DaneAge Association, which soon became a national cause with more than 200,000 members. The DaneAge Association operates as an association independent of the public authorities pursuing both local and national policies concerning the elderly and implementing humanitarian initiatives based on voluntary work. Studies made by the DaneAge Association show, among other things, that 20 per cent of the people aged 60 and over need practical assistance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1638884 TI - Changing elderly in a changing society. Danish elderly in the next century. AB - A cross-sectional and multidisciplinary study on the situation of the elderly in Denmark at the beginning of the next century was undertaken in the late 1980s. The intention was to give a picture of the future cohorts of elderly, and their expectations for old age. The study also looked into the ways in which future societal developments might affect the situation of the elderly. In order to test a number of hypotheses on the future elderly and their preferences for life when they grow older, 1200 persons in the age groups 40-44, 50-54, and 60-64 years old were interviewed. Further, a number of studies were commissioned on developments which may affect the elderly with regard to health, housing, family, work and retirement, financial conditions, leisure activities and political participation. A main conclusion is that the future elderly in most areas--be it financial conditions, health, housing education--will be in a more favourable position than their predecessors after retirement. But there will still be a minority who suffer a hard life. They are the people whose finances are weak, whose health is impaired, and who lack social contacts. PMID- 1638885 TI - Elderly people in a large Danish city. AB - The Aalborg Model of elderly care contains the following new concepts: It is a comprehensive system, including housing, activities, a food service, practical assistance, nursing care, physical rehabilitation and counselling. High priority is given to the earlier detection of illness and of special needs in an attempt to enrich the quality of life of the elderly and to reduce the cost of treatment. Suitable, independent housing for the elderly has been integrated into ordinary residential areas. The elderly choose their own housing and the assistance they require based on the principle that they will be given help to help themselves, no matter where they live. The former division between visiting nurses and nursing homes has been eliminated, and the elderly are no longer classified according to "diagnosis." One exception to this is the geronto-psychiatric patients who are cared for in special nursing homes. The various kinds of assistance give many options to choose from, regardless of where you live. The services offered are flexible and are provided according to need. They can range from the once a week delivery of frozen, ready-to-serve dishes to extensive care both day and night. Decisions regarding the content and extent of the services are made by members of the permanent staff and the group leaders in cooperation with the elderly users. The various kinds of assistance can be adjusted to suit changing priorities and are provided in accordance with the special character of a local district. One group leader in each district is responsible for coordinating the services. The users have great influence. PMID- 1638886 TI - Non-institutional care for the elderly. A Danish model. AB - A 4 year long Action Research Project including the reorganization and co ordination of services and facilities for the elderly had been conducted in a Danish municipality. The project was started in June 1984 when a conceptual framework was developed to establish the foundation for the design of the project. The concept of self-care and WHO's strategy "Health for all by the year 2000" were central aspects of the framework. Self-care is the process of choosing and deciding over our own bodies and lives. In a more institutionalized health care system, citizens are often not able to take part in the decision-making process, or only with difficulty. A survey study was conducted to assess the social and health service needs and wishes of persons over 67 years of age. Comprehensive interdisciplinary training of staff was carried out. During the latter part of this period, a 24 hour service was planned, and the former nursing home was converted into a health care centre, with sheltered flats, guests flats and a day centre, open to all citizens, irrespectively of age. Out of consideration for both the inhabitants of the former nursing home and the staff, who were to test both the new ways of working together and the new working methods the changes were initiated slowly with careful preparation and coordination among the respective parties.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1638887 TI - Housing of the elderly. AB - The housing conditions of the elderly in Denmark are undergoing rapid improvement. The main reason for this is that the first generations to benefit from the growth of prosperity that started in the 1950s are now joining the ranks of the elderly. Similarly, the oldest of the elderly population--many of whom live in some of the country's oldest, smallest and technically worst housing--are now dying off. Most of the new elderly generation own their own home, usually a detached house, and the vast majority of them must be expected to be extremely satisfied with their homes and to want to remain in them in their old age. However, this may present difficulties, partly because it requires a certain income and partly because the dwellings require quite a lot of maintenance, gardening, street-cleaning, etc. The general rule seems to be that the elderly mainly only move from a good, big home when they lose their husband or wife or reach a point at which they need more care. Danish policy on housing for the elderly attaches importance to supporting the elderly in their own homes, and the available resources are largely concentrated on this intention. Here at the beginning of the 1990s this policy has run into difficulties because it has led to the allocation of resources being slanted in favour of relatively well situated elderly people, while the weakest and poorest old people with the biggest need for care are not served satisfactorily.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1638888 TI - Special dwellings for the elderly. AB - The policy governing old people's housing is administered individually in the various Danish municipalities. Those municipalities with a high housing coverage give the widest scope with regard to suitable housing, frequently applying The Housing for the Elderly Act, with common housing and service areas generally available. This is not the case, however, with municipalities operating with low housing coverage where suitable nursing homes are usually available, but not to a degree sufficient to offset the difference. These conclusions were reached after a study to establish how the policy governing housing for the elderly is applied in the various municipalities following the 1987 amendment of the Act concerning the building of special housing for the elderly. PMID- 1638890 TI - Financial circumstances of the elderly in Denmark--now and in the coming years. Pension systems and other economic possibilities. AB - The situation concerning pensions in Denmark has been changing in recent years. There is a trend for the population itself has to pay into private pension to ensure a satisfactory financial situation after retirement. There are three categories of pensions and supplementary grants influencing the financial situation of the elderly: social-political grants, labour market political grants, and private arrangements. The national retirement pension is paid to everyone in accordance with certain rules. One condition is residence in Denmark for 40 years after reaching the age of 15. The pension age is 67 years. It is possible to receive early retirement pay or to obtain partial pension from the age of 60. This means that the age for retirement from the labour market on average is 62 years. Supplements to the national pension can be given as a net sum. Such a payment, however, makes it more difficult for the elderly person to overview his or her financial circumstances in retirement. The partial pension is a new form of pension which was introduced in 1986. About 2% of the 60-66 year olds have taken advantage of this possibility, most of them independent trade men. In contrast, 105,000 wage earners are receiving early retirement pay, which is based on unemployment insurance. Certain considerations apply when the social pension is paid in a gross amount. This amount will not be free of tax. A number of special grants for the elderly will be included in the gross amount of the social pension. A system of that sort will make the financial circumstances of the retired person more clear.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1638889 TI - Retirement from work. The recent lowering of retirement age--causes and consequences. AB - The recent change in early retirement is described and related to the development in social policy, labour market and individual attitudes towards work and retirement. Particular attention is given to the orientation toward life after work in relation to retirement. The development in retirement pattern is seen as an institutionalisation of early retirement. PMID- 1638891 TI - Geriatrics in the Danish health care system. AB - After having occupied a modest place in the Danish health system for many years, geriatrics now shows signs of stability and growth. Instruction in geriatrics has been strengthened by the creation of a professorship in 1991. Structural changes, particularly in the Copenhagen hospital system since 1987, have given geriatrics a more prominent place, and from 1992, there will be more emphasis on this field. There has been increased interest in geriatrics in the primary health care sector on the part of general practitioners and home nurses. Geriatrics in the hospital sector takes the form of separate departments in large acute hospitals and independent hospital units and elsewhere is seen as a part of departments of internal medicine. In Denmark, the geriatric patient is a patient with many concomitant physical and psychic illnesses and the resultant social problems. Acute organ specific problems are generally taken care of outside of geriatric departments. PMID- 1638892 TI - Dementia in Denmark from a medical view. AB - The field of psychogeriatrics, including diagnosis and treatment of age associated dementia, is still in its early years in Denmark. Most of the treatment of the elderly with psychiatric conditions lies in the hands of general practitioners and staff of somatic nursing homes. In a few places in Denmark, a more academic approach to the elderly patients has developed in general psychiatric hospitals. Psychogeriatric department D at The Psychiatric University Hospital in Arhus is an example. Treatment ideology, strategies, education, outpatient treatment and hospital-treatment is described, especially regarding age-associated dementia. PMID- 1638893 TI - Improving environment and care for elderly people with dementia. AB - The increasing number of demented elderly people makes it necessary to develop new ways of organising care for this particular group, which up to now has not attracted much interest amongst old-age policy decision makers. The life of the demented and their relatives can be improved by developing environments with suitable physical, social and psychological elements. Such efforts can contribute to better maintaining the abilities of the demented person instead of reducing them further. The everyday life can be organised in small units, where the staff is specifically trained to care for the demented. This approach is now being tried in nursing homes, dementia groups, and collective housing projects. PMID- 1638894 TI - Preventive home visits among elderly people. AB - Recurrent preventive home visits are an important part of the efforts for elderly people in about 15% of the communities in Denmark. Based on these experiences, this paper describes how to conduct the preventive visits. The content consists of structured conversations, attention to possible risk situations, action proposals and followup on previous discussions and planned changes. The empathy of the visitor is an important factor. A hypothesis is proposed about the cause of the positive effect of the preventive visits on institutionalisation and mortality. PMID- 1638895 TI - Involvement. Senior citizens' recreational activities. AB - During the last 18 years, senior citizens in Viborg, Denmark, have participated in study circles based on the theory of impression pedagogy and socially relevant activities. They arrange excursions at home and abroad and make films about the trips. They teach schoolchildren, students at folk high schools, and nurses, as well as occupational therapists and physiotherapists. They publish poems and books, write role plays, stage musicals, sing in choirs, and function as tour guides in town. They set up educational color slide programmes on preventing bone fractures, dealing with the problem of reduced hearing, and the importance of healthy food and exercise. They travel abroad and talk about Denmark and the conditions for senior citizens in our country. With the support of the Danish Ministry for Social Affairs, they produce videos about their activities as a source of inspiration to others. The use of drugs by the participants in the study circles has declined, while the level of activities has increased, and none of the participants has ever had to enter residential care. PMID- 1638896 TI - The elderly at folk high schools. An educational experience. AB - The following article tells about a special feature of Danish society, namely the Danish Folk High School. The traditional folk high school has existed since the era of Grundtvig, but after 1970, efforts were made both by means of hard work and by legislation so that today we are able to offer courses for our senior citizens at four different high schools. Rapid technical development threatens to bring our society into imbalance. One can fear that the spiritual world, overrun by technocrats, is close to break down. However, the Danish folk high school affords an enormous chance to fight back by helping people to reestablish their self-reliance, appreciating human values like solidarity and the exchange of thoughts and dreams. The Danish folk high school is one possible antidote for a world of too much body and too little spirit. PMID- 1638897 TI - Care for the dying in Denmark. AB - In Denmark terminal nursing and care (TC) have become a hospital duty during the last four to five decades. The terminal stage of the elderly is hard to delimit. Death often comes undramatically and unpredictably. Many are found dead in their beds in the morning without any preliminary complaints. In 1989, 63% of all deaths occurred in hospitals, 78% of which were persons over 65 years old. Seventeen per cent died in rest homes, and only about 5% died a planned death in their homes. TC can be considered from four different angles: communication, practical arrangements, pain treatment, nursing and care. A definition of the general demands for the care offer is made, and the development of TC in Denmark is explained, extended home care nursing arrangements with care 24 hours day, better pain control, introduction of support for nursing the dying at home. Thus, dying at home is now an actual alternative to institutional death. PMID- 1638898 TI - Legal and ethical aspects of Danish elder policy--progress, dilemmas, and challenges. AB - The article deals with the fundamental principles of Danish social and health law: individual rights to basic benefits for all elderly citizens, but also a right to supplementary benefits earned by one's own efforts. The principle of informed consent has been accepted by the medical and legal professions and has, from there, spread to care giving activities within the social services. There are many unsolved ethical and legal problems concerning the care of the frail and vulnerable elderly, especially those who are not capable of giving or refusing consent. PMID- 1638899 TI - The new social and health education programmes. AB - On 1 January 1991, a comprehensive restructuring of the basic social and health education programmes in the fields of assistance, nursing, and care was carried out in Denmark. This article briefly describes the background and contents of the new educational programmes. PMID- 1638900 TI - Habits and rituals. AB - On-going restructuring in the Danish care for the elderly is to a very high degree based on recognition of the significance of habits and rituals, as well on the knowledge of what is needed to alter them. Habits and rituals are concepts that are often confused in everyday patterns of thought. It is necessary to be able to distinguish between the two concepts before change can be effected. To varying degrees people are characterised by unconscious and conscious habits as well as inherited and personal rituals. Personal development, age, support from one's surroundings, and so on, determine the degree to which a person may continue or alter acquired patterns of habit and ritual. PMID- 1638901 TI - The privileged old in Denmark. AB - The author builds on personal experience as a retired civil servant. He has been the initiator of the Academy for the Third Age and, as chairman of The Danish Social Political Association, has worked with the problems of the elderly. In his attempt to describe the situation of privileged elderly citizens, he has tried to emphasise that their limited time perspective urges them to live one more life of intense experiences. The freedom which they have acquired with retirement makes this easier to achieve. PMID- 1638902 TI - When staff members sexually abuse children in residential care. AB - When an agency staff member is accused of sexually abusing a client, the administration is faced with the Solomonic task of balancing the necessity of protecting the child, supporting the staff, and maintaining the integrity and reputation of the agency. This article presents practical suggestions for managing the agency through such a crisis. PMID- 1638903 TI - Critical issues in residential care for young mothers and infants: an overview of model licensing rules. PMID- 1638904 TI - Traumatic bonding: clinical implications in incest. AB - The concept of traumatic bonding, taken from the literatures on trauma, victimization, and exploitation, holds promise for explaining some of the more confusing dynamics of incest. This article offers a definition of traumatic bonding, demonstrates how it can be applied in cases of incest, and discusses the implications of this concept for therapeutic intervention. PMID- 1638905 TI - Implementing critical health services for children in foster care. AB - This article reports recommendations that were developed at the California Conference on Health Care for Children in Foster Care, organized to discuss implementation in the state of CWLA's Standards for Health Care Services for Children in Out-of-Home Care. Programs and legislation developed in the state are also discussed. PMID- 1638906 TI - The Child Well-Being Scales: a field trial. AB - The Child Well-Being Scales [Magura and Moses 1986] were developed to evaluate programs of child welfare services. Although appealing in format, the scales have lacked adequate validation. For the field trial reported here, 17 of the scales were extracted and used to form measures of physical and psychological care of children. A comparison between families identified as neglectful and low-income control families yielded differences in the predicted direction. The composite indices showed good internal consistency. The concurrent validity of this segment of the scales was supported. The scales yielded three factors that reliably classified families externally verified as neglectful and nonneglectful control families. PMID- 1638908 TI - Cocaine in perspective. AB - In a medical text published in 1883, Dr Benjamin Ward Richardson FRS denounced the evils of tea drinking, suggesting that it commonly gave rise to an 'Extremely nervous semi-hysterical condition'. That this distinguished Victorian physician could take such a view invites a sensitivity toward the perspective within which any debate on drugs is conducted--the historical, cultural and professional assumptions which will colour views as to what needs to be explained and how explanation is to be accomplished. The reality and significance of 'perspective' is further illustrated by examples drawn from contemporary literature which contrast the laboratory and social science approaches to study of cocaine. No one narrow disciplinary perspective on the cocaine problem will suffice; the challenge is to build bridges. PMID- 1638907 TI - Reactions by Native American parents to child protection agencies: cultural and community factors. AB - The oppression suffered by Native Americans has so undermined their culture and ability to parent that child abuse and neglect are frequent problems. Yet the history of oppression often seriously damages the capacity of many Native American parents to accept help from child protective service agencies and staff members. This article explains the particular characteristics and behaviors of some Native American parents, and closes with a summarized guide to understanding these parents and to appropriate behavior on the part of social workers. PMID- 1638909 TI - How toxic is cocaine? AB - The toxicities of cocaine are far-ranging. They include sudden death, acute medical and psychiatric illness, infectious complications, reproductive disturbances, trauma, criminal activities and societal disruption, including child neglect and abuse and lost job productivity. This chapter focuses on the medical complications. Medical complications in general reflect the intense sympathomimetic activities of cocaine ('sympathetic neural storm'). Psychiatric complications include acute anxiety or panic and paranoid psychosis. Cardiovascular complications include arrhythmias and sudden death, acute myocardial infarction, myocarditis, dissecting aneurysm and bowel infarction. Neurological complications include seizure, intracerebral haemorrhage and brain injury due to hyperthermia and/or seizures, and headache. The incidence of medical complications has been estimated using two databases collected prospectively in the United States. In 1989 and 1990 cocaine ranked first in total encounters, major medical complications and drug-related deaths. An attempt was made to assess the intrinsic toxicity of cocaine by computing the incidence of adverse health outcomes per population of drug abusers. Rates of emergency department visits and deaths were 15.1 and 0.5 respectively, per 1000 persons using drugs in the past year. The magnitude of the cocaine problem, while considerable, is relatively small compared with that of cigarette smoking or alcohol abuse. PMID- 1638910 TI - Determinants of cocaine self-administration by laboratory animals. AB - The reinforcing effect of a drug is that effect that increases the probability that the drug will be self-administered again. Like other drug effects, a reinforcing effect is the result of an interaction between organism, drug and environment. Laboratory research using animal subjects has helped elucidate the contribution of each of these factors to the self-administration of cocaine. A substantial amount of research indicates that increased dopamine neurotransmission in the brain, particularly in mesolimbic and mesocortical regions, plays a major role in cocaine self-administration. Both indirect and direct dopamine agonists can function as positive reinforcers in animals, whereas noradrenergic and serotonergic (5-HT, 5-hydroxytryptamine) agonists have not been found to do so. In addition, evidence suggests that dopamine but not noradrenaline (norepinephrine) or serotonin antagonists can attenuate the reinforcing effect of cocaine. Environmental factors have also been shown to be critical determinants of the reinforcing effect of cocaine. The schedule of reinforcement essentially determines the rate and pattern of drug-maintained behaviour. In addition, punishing self-administration, increasing the value of alternative reinforcers that are available, and increasing the cost of cocaine have all been shown to decrease the reinforcing effect of cocaine. With regard to organismic factors, recent research has suggested that there are significant genetic determinants of cocaine consumption. Taken together these research findings in animals imply that certain individuals may be more sensitive to the reinforcing effect of cocaine but that cocaine abuse can be decreased by pharmacological or behavioural means or by a combination of the two. PMID- 1638911 TI - Self-administration of cocaine by humans: a laboratory perspective. AB - Laboratory research evaluating the behavioural and physiological effects of cocaine has produced important basic information relevant to the prediction and control of cocaine abuse. Adaptation for human subjects of laboratory procedures originally developed with non-humans has provided the methodology for assessing the relationship between cocaine-taking and the self-reported effects of cocaine. This laboratory model for evaluating drug-taking has been adapted to include all the routes of administration by which cocaine is abused. Data collected in cocaine choice/self-administration studies indicate that there is a generally good correlation between cocaine self-administration and its stimulant-like 'positive' effects. There are, however, areas in which these two measures clearly diverge, and drug self-administration procedures provide a sensitive measure of cocaine's effects when it is taken by the routes and in the patterns people use outside the laboratory. Combining these measures with other behavioural evaluations provides useful information for understanding cocaine use and abuse. In addition, and importantly, these laboratory procedures are useful tools in the development and assessment of treatment interventions which might be used effectively. PMID- 1638912 TI - AIDS and HIV infection in cocaine users. PMID- 1638913 TI - Treatment of cocaine abuse: pharmacotherapy. AB - Until recently the treatment of cocaine addicts was limited to non pharmacological methods because cocaine abuse was viewed as a psychological addiction to the drug's euphoriant effects. Chronic stimulant abuse is now known to lead to neurophysiological adaptation. This physiological evidence, and the failure of many patients to respond adequately to psychological treatment, prompted clinicians and researchers to explore numerous pharmacological agents in the early 1980s. Promising medications that may affect the euphoria, the craving, withdrawal, or the toxic effects associated with cocaine are under development. Potential pharmacological agents being studied include tricyclic antidepressants, anticonvulsants, neurotransmitter precursors, stimulants and dopamine agonists, serotonin re-uptake blockers and agonists, neuroleptics and opioid agonists/antagonists. Most of the research to date is on anti-craving agents. While many positive clinical reports exist, most reports are anecdotal and uncontrolled. The available data are reviewed. Potential pharmacotherapies require further research to elucidate the differences between treatments, the target populations, the optimal dosages and duration, and the interaction with behavioural and psychotherapeutic approaches. PMID- 1638914 TI - Epidemiological research on cocaine use in the USA. AB - In the study of cocaine, epidemiology offers a way to reckon the experience of human populations, from time to time, from region to region, from community to community, and from group to group. Continuing surveillance of cocaine experiences in diverse segments of the United States population has allowed us to plot the course of our most recent cocaine epidemic in more detail than in the past. Still, much remains to be learned about the dynamics of the cocaine epidemic before public health agencies or anyone else should ride to glory on the descending limb of this epidemic curve. Beyond basic surveillance, epidemiology has the capacity to teach us about the conditions under which human cocaine use starts, is maintained, and stops, including the array of perceived and actual consequences of cocaine use that may determine specific patterns of use. In this respect, there is some value in making a chronicle of cocaine users' life experiences, with a comparison to the life experiences of others. However, the perceptions of cocaine users do not always map onto observations made under controlled conditions of laboratory research. Finally, it is not essential for epidemiology to rely solely upon what individuals perceive and report as causal linkages between cocaine use and their other life experiences. One effective alternative is to use the epidemiological case-control method and related strategies to probe suspected causal linkages involving cocaine. As demonstrated in recent research, these strategies have a resolving power that goes beyond that of standard epidemiological survey reports. Of course, the resulting epidemiological evidence does not stand alone. Rather, it complements laboratory and clinical research, giving a more complete view of cocaine's impact on human health. PMID- 1638915 TI - Psychotherapy for cocaine dependence. AB - Dependence on cocaine is a new disorder for contemporary US clinicians. Until the 1980s sufficient quantities of the drug were not available to produce a true dependence. Thus far the only models for pharmacological intervention involve an interaction between medication and psychotherapy; that is, medication may be able to facilitate a drug-free interval during which time the patient can be engaged in psychotherapy. Psychotherapy programmes for cocaine dependence have generally been modelled on group-oriented treatments of the type used by Alcoholics Anonymous. Controlled studies of therapy programmes for cocaine dependence are currently being conducted and one prospective random-assignment study comparing day hospital and in-patient rehabilitation shows generally good results. Behavioural treatments aimed at reducing or extinguishing conditioned responses in cocaine addicts have also shown efficacy in a controlled study. More general relapse prevention procedures including rehearsal and role-playing are also used in the treatment of cocaine dependence. Combinations of psychotherapy and pharmacotherapy have so far shown the most promise in the treatment of this disorder. PMID- 1638916 TI - Alternative strategies. AB - Drug treatment alternatives in the United States are constrained by what is politically correct and expedient and by a federal policy of 'zero tolerance' for any illicit psychoactive drug use. A war on drugs will not solve all the problems posed by cocaine. Alternative strategies must address fundamental problems in ghetto life: violence, poverty, poor health, no education, no jobs, and few reasons for not taking drugs. Despite warnings of pharmacological determinism, cocaine is like other psychoactive drugs. Even with cocaine, when alternative behaviours are possible most people avoid out-of-control use. Public health strategies promoting a harm-reduction policy offer advantages. Recent reductions in cocaine use are a consequence of education, awareness of good health practices, and interest in other activities. Alternatives could include cocaine in a safer, non-lethal and controllable form but are unlikely in a political climate where politics and law prevail rather than medicine and humanity. PMID- 1638917 TI - The economics of drug use and abuse. AB - The markets for drugs such as cocaine are characterized by much ignorance about the nature of trading relationships, in particular the volumes and prices exhibited by overlapping national and international networks of buyers and sellers (i.e. markets), and by severe regulation by the State. The regulation of illegal markets is expensive; for example, in 1988 in the UK, over 5000 Customs officers and 1800 CID and uniformed policemen were involved in enforcing the law at a cost of about 140 million pounds. The size of the markets can be only 'guesstimated': in 1989 just over 520 kg of cocaine was seized. If this is assumed to be 10% of the market, the total size of the cocaine market was somewhere in excess of 5000 kg. The 'cost-effectiveness' of both Customs and the police in enforcing the law may have declined in the late 1980s. What economic arguments are there for sustaining illegality and an expensive enforcement effort? Some arguments for State regulation are explored; for example, the drug user harms 'innocent' third parties, the drug user is less productive and reduces national income, the drug user will impose costs on the National Health Service, the drug user's behaviour is offensive, and the drug user should be protected from his own stupidity. Where do these arguments leave the case for maintaining public policy towards illicit drugs? Would it be cost effective to move towards the liberalization of these markets? PMID- 1638918 TI - Formulating policies on the non-medical use of cocaine. AB - The formulation of policy on cocaine, as on any other social issue, involves explicit or implicit cost-benefit analyses with many factors. Cocaine use carries many medical, psychiatric and social risks, and its inherent pharmacological risk of dependence is greater than for other drugs. The reported frequency of these problems has increased exponentially over the past fifteen years. However, current levels of use are decreasing in the general population, though still increasing among certain subpopulations in which it is accompanied by violent crime. On the other hand, the attempt to control use mainly or exclusively by reducing the supply has been of low efficacy and extremely expensive, in both human and monetary terms, for the consuming countries and economically and politically devastating for the producing countries. Yet past experience with other drugs suggests that legalization of cocaine would increase its use substantially. Moreover, legalization runs counter to public sentiment, even in those countries where the law is applied leniently against users and small-scale traffickers. The most practical policy appears to be to maintain prohibition as a sign of social disapproval, but to rely much more heavily on non-coercive measures to reduce demand by strengthening public consensus against all drug use. PMID- 1638919 TI - Drug use and abuse: the ethical issues. AB - Drug abuse is both a personal and a public issue, raising questions about individual rights and the boundaries of law, as well as about national sovereignty and international control. Ethical issues that arise under these headings may be related to certain broad ethical positions. The implications of adopting utilitarian assumptions may be contrasted with basing ethics on a theory of individual rights, closely related to a theory of human nature. Neither position justifies a libertarian presumption against control, for, first, an individual decision to expose one's mind and personality to the control of drugs cannot be ethically justified and, second, there are no ethical reasons, nor any compelling arguments from social and political theory, for decriminalizing non medical drug use. PMID- 1638920 TI - Cocaine problems in the coca-growing countries of South America. AB - The problems of cocaine present a rather particular profile in the Central Andes region from which this drug originates. On the one hand there is a relatively harmless pattern of use (coca leaf chewing) in the countries concerned which minimizes the drug's most hazardous properties. On the other hand the region suffers from some of the most severe cocaine-related problems to be observed anywhere: (a) easy access to the newer, highly toxic preparations of the drug (such as coca paste) and a rapid growth in the number of new users; (b) the abandonment of certain traditional and essential agricultural activities in favour of the more profitable coca leaf production; (c) the severe ecological damage being caused in the coca growing areas; and (d) the establishment of a powerful coca trade economy which is subverting the very fabric of society and is creating corruption, lawless violence and political anarchy. PMID- 1638921 TI - Are there 'casual users' of cocaine? AB - Medical and public opinion about cocaine use have shifted dramatically over the past decade. New research methodologies and definitions to evaluate the impact of cocaine are needed. This paper presents a theoretical definition and empirical analysis of the 'casual user' of cocaine. Data have been drawn from a subsample of 58 cocaine users and their cocaine-using contacts in Rotterdam. The methodology of the study presents a novel approach to patterns of cocaine use involving the integration of social network variables with 'snowball' sampling data collection techniques. The theoretical definition is systematically related to two social context variables: (1) the scope of settings where contacts use cocaine; (2) the degree of involvement in social network relations of actual cocaine use. Scope of settings has been defined in terms of the number of cocaine using social circuits contacts are drawn from: i.e. 'narrow' setting where all contacts originate from one circuit while a 'wide' setting indicates contacts come from two or more circuits. Involvement has been defined in terms of the percentage of contacts where the relation with study participants is characterized by cocaine use most or all of the time. Additional social network variables measuring the mean duration (in years) of contacts' cocaine use and the use of cocaine with contacts in the last six months are subsequently related to the scope and involvement variables. The implications of the analysis for a new cross-classification of cocaine use patterns are discussed with special reference to public health policy issues. PMID- 1638922 TI - Cocaine's history, especially the American experience. AB - The history of cocaine in America can be traced to the late 19th century. After the discovery of its physiological and psychological effects, cocaine figured in consumables as diverse as hay fever remedies, local anaesthetics and soft drinks. The development of its different usages as well as eventual control of its use through restrictive legislation followed a different pattern in America from that in Europe. In the United States, national laws to control drugs faced constitutional obstacles until the era of World War I. Initially acclaimed as an ideal tonic, within two decades of its introduction in the mid 1880s cocaine was perceived as an extremely dangerous drug. By the 1930s cocaine had declined in use and in the 1960s, when it gradually emerged again, almost no public memory existed of the earlier 'epidemic'. Once again this substance evolved into a threatening and seductive hazard with some similarities to the earlier episode. PMID- 1638923 TI - Molecular pharmacology of cocaine: a dopamine hypothesis and its implications. AB - The reinforcing properties of cocaine have been related to cocaine binding at the dopamine transporter in mesolimbocortical neurons. The molecular properties of the transporter have been studied in a number of laboratories. While this 'dopamine hypothesis' is strongly supported in animal studies of drug self administration, the extent of its involvement in human drug dependence has not been fully elucidated. PMID- 1638924 TI - The neurobiology of cocaine-induced reinforcement. AB - Cocaine has potent pharmacological actions on a number of monoaminergic systems in the brain, including those that use noradrenaline, dopamine and serotonin as neurotransmitters. There is growing evidence that cocaine's effects on dopaminergic neurons, particularly those that make up the mesolimbic system, are closely associated with its rewarding properties. For example, low doses of dopamine receptor antagonists reliably influence cocaine self-administration, whereas noradrenaline and serotonin receptor antagonists are without consistent effects. Similarly, selective lesions of dopaminergic terminals in the nucleus accumbens, a major target of the mesolimbic dopamine projection, disrupt cocaine self-administration in a manner that is consistent with loss of cocaine-induced reward. The introduction of in vivo brain microdialysis as a tool with which to investigate the neurochemical correlates of motivated behaviour has provided new opportunities for investigating the role of dopamine in the nucleus accumbens in the acquisition and maintenance of cocaine self-administration. Although the body of literature that has been generated by this approach appears to contain some important inconsistencies, these probably reflect the use of inappropriate microdialysis conditions by some investigators. A critical review of the literature suggests that microdialysis results are generally consistent with a role for mesolimbic dopamine in cocaine-induced reward, although it does not seem to be the case that animals will work to maintain consistent increases in extracellular concentrations of dopamine in the nucleus accumbens in all experimental conditions. Elucidation of the complete neural circuitry of cocaine induced reward remains an important priority for future research. PMID- 1638925 TI - Toxic effect of endocytobionts from Dermacentor reticulatus ticks in three tick species after in vivo application. AB - The endocytobionts from ovaries of partially engorged female Dermacentor reticulatus ticks, inoculated introcoelomally into females of three tick species, D. reticulatus, Ixodes ricinus and Haemaphysalis inermis, caused considerable morphological alterations in the examined cells and tissues of the synganglion, fat body, tracheal complex and ovary of these recipients. PMID- 1638926 TI - Effects of precocenes on vitellogenesis in the adult female tick, Ornithodoros moubata (Acari: Argasidae). AB - Vitellogenin (Vg) concentrations in the hemolymph and ovarian development were studied in Ornithodoros moubata after treatment with precocenes 1 (P1) and 2 (P2). Precocene was dissolved in acetone or DMSO and topically applied to the dorsal surface of ticks: (1) at adult ecdysis; (2) 24 h before engorgement; (3) immediately after engorgement; and (4) 24 h after engorgement. Subsequently, P1 and P2 were dissolved in olive oil and injected through the gonopore into the body cavity 24 h after engorgement. Vitellogenin concentration was measured on days 5 and 10 after engorgement and ovarian development was scored on day 10, 20 or 30. Oviposition was also recorded and the average weight of eggs laid by females was determined. No differences in concentration of Vg in the hemolymph occurred between the control ticks and ticks treated topically or by injection with P1 and P2. Precocene did not suppress the synthesis of Vg in O. moubata. However, oviposition was reduced in ticks that survived repeated treatment with high doses of P2 dissolved in acetone. PMID- 1638928 TI - Morphology and structural organization of spiracles in female Argas (Persicargas) walkerae (Acari: Argasidae). AB - Scanning electron microscopical investigations of fractures and corrosion casts of the spiracles from female A. walkerae ticks revealed a four-part structure, consisting of spiracular plate, ostium and macula forming the external closure, followed by the subostial space and the vestibulum of regulable volume, as well as the atrial chamber as the innermost part from which the main tracheal trunks originate. On the average, the spiracular plate was 158 microns long and 188 microns at the broadest width. It consisted of a thin, highly perforated external and a thick internal layer, which enclosed the interpedicellar space with numerous stout pedicels. In its posterior region, the spiracular plate was covered by the macula, which was up to 80 microns in length and 110 microns in width. The interpedicellar cavity opened into the subostial space measuring 95.5 microns in length and 159.6 microns in width, which proceeded into the 112 microns long vestibulum. The roof of the vestibulum was flexible and could be everted and inverted. Inverted, the roof formed a quadratic bulge with numerous deep cuticular folds, which confined the lumen of the vestibulum either partially or completely. In corrosion casts, the roof was everted to a length of up to 89.3 microns. In the posterior part of the vestibulum, as well as in the initial fourth of the atrial chamber, numerous anvil-, cone- or drop-like cuticular projections were arranged in wedge-like fashion. The atrial chamber was almost spherical with a diameter of 138.4 microns. Five main tracheal trunks of different luminal diameter as well as numerous channels opened into the atrial chamber. PMID- 1638927 TI - Observation on the composition and biosynthesis of egg wax lipids in the cattle tick, Boophilus microplus. AB - The biosynthesis of wax lipids by Gene's organ, the egg waxing organ in ticks, was investigated. Gene's organ, a complex dermal gland system, applies a superficial wax layer to the eggs during oviposition which prevents desiccation and is essential for egg viability. The detailed anatomy and histology of the three gland cell types are unambiguously described. Serial sectioning of ticks showed that all three gland cell types are capable of contributing to the egg wax. The wax synthetic ability of these three gland types was characterized. The composition of wax lipids extracted from the surface egg wax, and from the three types of wax gland dissected from ovipositing ticks, was analysed using thin layer and gas-liquid chromatography. Injection of ovipositing ticks with radiolabelled acetate resulted in the incorporation of the label into wax lipids by gland cells of Gene's organ. The egg wax was a complex mixture of long-chain alkanes and fatty acid esters. The gland cells contained a greater proportion of shorter chain alkanes than were present in the egg surface wax. Some unsaturated long-chain fatty acids were present, and these were more abundant in the gland cells than in the surface wax of oviposited eggs, suggesting that oxidation occurs after oviposition. The results confirm that the tubular glands, acinar accessory glands and lobular glands of Gene's organ all contribute to the egg waxes, although the lipid components differed in relative abundance. The results are also consistent with alkane synthesis from fatty acids in Gene's organ by a chain-elongation-decarboxylation pathway. PMID- 1638929 TI - A comparison of methods for sampling the deer tick, Ixodes dammini, in a Lyme disease endemic area. AB - The purpose of this study was to compare the trapping and examining of mice, drag sampling, and CO2-baited traps for their ability to detect the presence and abundance of immature deer ticks, Ixodes dammini, in a Lyme disease endemic area in southern New York State. Eight study sites were sampled 14 times between 28 May and 31 August by setting 49 live-traps, four CO2-baited traps, and drag sampling 500 m2. A total of 1540 nymphs and 3079 larvae was collected during the study. Drag sampling collected the most nymphs (705), while more larvae were recovered from CO2-baited traps (1105). Comparisons among the methods showed a significant difference in the numbers of both larval and nymphal ticks collected (P less than 0.01). There was a positive correlation between the numbers of nymphs collected by drag sampling and CO2-baited tick traps (rs = 0.83, P less than 0.05), and between the numbers of larvae collected by drag sampling and mouse trapping (rs = 0.75, P less than 0.05). These results suggest that drag sampling would be the single most reliable method for quantitatively sampling immature I. dammini populations in a Lyme disease endemic area. PMID- 1638930 TI - Prognostic factors in breast cancer: integrating the cytology laboratory. PMID- 1638931 TI - Diagnostic accuracy of fine-needle aspiration cytology in persistent or recurrent gynecologic malignancies. AB - A retrospective 7 1/4-yr study was performed to evaluate the diagnostic accuracy of fine-needle aspiration (FNA) cytology in the cell typing of persistent or recurrent gynecologic malignancies. A total of 202 aspirates were obtained from 163 patients with documented malignancies of the cervix, uterus, ovary, vulva, and vagina. Information concerning the primary tumor was obtained from surgical reports and/or medical records. In 168/202 cases (83%), the histological diagnosis, including primary tumor cell type and subtype (ex. squamous cell carcinoma, large cell keratinizing), were available. In 12/202 cases (6%), only the tumor cell type (ex. squamous cell carcinoma) was known, and in the remaining 22 cases (11%), only the location of the primary neoplasm was attainable. Aspirated sites included pelvic wall and organs (77 cases), lymph nodes (51 cases), thoracic organs (18 cases), and abdominal wall and organs (56 cases), including liver (33 cases). Of the 168 cases with known histologic diagnoses, the FNA results were positive in 109 (65%). The positive results were divided into three groups: group I, the cytologic findings were predictive of the histologic diagnoses (84 cases, 77%); group II, tumor cell subtyping was not possible on cytology (17 cases, 16%); group III, neither tumor cell typing nor subtyping was possible on cytology (8 cases, 7%). Of the 34 cases in which only the histologic tumor cell type or primary tumor location was known, 13 (38%) were positive on FNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1638932 TI - Needle aspiration cytology of the irradiated breast. AB - During a 3-year period (1987-1989), 60 fine-needle aspiration biopsies (FNAs) were obtained from new breast lesions in patients previously treated by radiation and surgery for breast carcinoma. The lesions occurred at or near the site of previous excision, 3-117 months after initiation of radiotherapy. FNAs were classified as follows: acellular (11); negative (29); atypical (13); suspicious (4); and positive (3). For statistical analysis, acellular, negative, and atypical diagnoses were considered negative findings, and suspicious and positive diagnoses were considered positive findings. On the basis of subsequent biopsy and/or patient follow-up, FNA yielded a sensitivity of 86%, a specificity of 98%, a positive predictive value of 86%, a negative predictive value of 98%, and an efficiency of 97%. Excluding cystic lesions, the most reliable criterion for distinguishing malignant from benign lesions was the abundance of epithelial cells, both singly and in large clusters. Cellular characteristics were less helpful, since nuclear atypia was seen in both benign and malignant lesions. It is concluded that (1) FNA is a reliable technique in the evaluation of the irradiated breast; (2) when performed by an experienced operator, an acellular aspirate may be interpreted as evidence against recurrent carcinoma; and (3) epithelial atypia must be interpreted with caution to avoid a false-positive diagnosis. PMID- 1638933 TI - Cytopathology of malignant mesothelioma: a stepwise logistic regression analysis. AB - Twenty-four cytologic features, previously reported to be useful in the distinction of malignant mesothelioma, adenocarcinoma, and benign mesothelial proliferation in serous effusions were assessed. Forty-four cases of malignant mesotheliomas, 46 cases of metastatic adenocarcinomas, and 30 cases of benign mesothelial proliferations were examined for these parameters. When these cytologic features were subjected to a stepwise logistic regression analysis, five features were selected to distinguish malignant mesothelioma from adenocarcinoma. These were true papillary aggregates, multinucleation with atypia, cell-to-cell apposition, acinus-like structures, and balloon-like vacuolation, the latter two features being characteristic of adenocarcinoma. The four variables selected to distinguish malignant mesothelioma from benign mesothelial proliferations were nuclear pleomorphism, macronucleoli, cell-in-cell engulfment, and monolayer cell groups, the latter being a feature of benign proliferations. Using these selected variables, the logistic model correctly predicted 95.4% of cases of malignant mesothelioma versus 100% of adenocarcinoma and 100% of malignant mesotheliomas versus 90% of benign mesothelial proliferations. The results of regression analysis suggest that many of the previously described cytologic features are not important diagnostic discriminators. PMID- 1638934 TI - Columnar cells in posthysterectomy vaginal smears. AB - Columnar cells in posthysterectomy vaginal smears are unusual and rare. Nine such cases are reported here during a 6-yr period. All nine patients were asymptomatic and total hysterectomy with bilateral salpingoophorectomy for gynecological malignancies was performed 8 mo to 25 yr ago. Three patients had local radiation and one had systemic chemotherapy not less than 8 mo before the cytology. The columnar cells showed one of three patterns: 1) long, bipolar cells in sheets, resembling reparative columnar cells (4 cases), 2) goblet-type cells with eccentric nuclei (3 cases), and 3) tight clusters of small round cells (2 cases). No consistent relationship with age, treatment, or background was seen with any of the patterns. Follow-up of all cases by thorough pelvic examination, repeat smears, colposcopy, and biopsy showed no vaginal pathology. Benign mucinous or goblet cell metaplasia in atrophic vaginal epithelium may be the source of some of these cells in the vaginal smears. PMID- 1638935 TI - Nucleolar organizer regions in FNAC smears of breast lesions. AB - The argyrophil technique for staining proteins associated with nucleolar organizing regions was applied to the fine-needle aspiration cytology smears of 45 cases of breast disease. These included 14 malignant and 31 benign lesions. A correlation with histology sections was done in 12 cases. There was a significant difference between AgNOR count of benign and malignant breast disease with one case out of 45 falling in the "gray" zone of overlap. Infiltrating lobular carcinoma was found to have the lowest NOR counts among the malignant lesions. The smear staining was superior to that on sections, the positive features being lack of background staining and better dispersion of NORs in the nucleoli. PMID- 1638936 TI - Aspiration cytodiagnosis of breast carcinoma in pregnancy and lactation with immunohistochemical and electron microscopic study of an unusual mammary malignancy with pleomorphic giant cells. AB - We have reviewed our experience with 8,706 needle aspiration cytology (NAC) of the breast which were done from January 1983 to June 1991. During our study we diagnosed four cases of breast carcinomas (three ductal type and one with pleomorphic giant cells) in pregnant or lactating women; in all of these the cytologic findings corresponded with the subsequent tissue diagnosis and cell block preparations. Considering that carcinoma of breast during pregnancy and lactation is rare and is second only to cervical cancer, it was felt that its diagnosis by NAC was useful for timely management. In the case in which pleomorphic giant cells were present as an integral component of the tumour, immunohistochemical and electron microscopic study was done. This is discussed in view of our recent experience with this unusual tumour. PMID- 1638937 TI - Cytologic diagnosis of malignant mesothelioma in serous effusions using an antimesothelial-cell antibody. AB - Differentiating mesothelioma, reactive mesothelium, and adenocarcinoma in serous effusions is often difficult, despite the application of ancillary techniques in support of the traditional cytomorphologic criteria. A polyclonal antimesothelial cell antibody recently developed by our group was evaluated as a histogenetic marker on a series of primary (n = 12) and metastatic (n = 12) malignant effusions. Immunostaining was performed on paraffin sections from cell blocks. All mesothelioma effusions stained positive for the antibody, whereas, in contrast, all metastatic carcinoma specimens failed to react. These results (100 percent specificity and 100% sensitivity for mesothelioma) provide a basis for a reliable use of the antibody in the cytologic examination of suspicious or malignant serous effusions. PMID- 1638938 TI - Simultaneous fine-needle aspiration of thyroid lesions and regional cervical lymph nodes: clinicopathologic implications. AB - Occasionally patients with thyroid nodules to be evaluated by fine-needle aspiration (FNA) biopsy also present with regional cervical lymphadenopathy. Aspiration biopsies should be performed on both the thyroid and nodal lesions. This approach will yield important information about whether the lesions are related, with profound impact on further workup, management, prognosis, and staging. PMID- 1638939 TI - Fine-needle aspiration biopsy of hepatic angiosarcoma: report of a case with immunocytochemical findings. AB - Hepatic angiosarcoma (Kupffer cell sarcoma) is a very rare but ominous malignancy. We report a case diagnosed by fine-needle aspiration biopsy (FNAB). The smear showed malignant spindle cells and a few rounded cells. The diagnosis was made on the cell block by the characteristic scaffolding arrangement of malignant cells along preexisting hepatocytes. This is the first report with immunocytochemical findings. The tumour cells stained positively for vimentin and negatively for keratin, factor VIII, Ulex europaeus agglutinin I (UEA-1), carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and lysozyme. This case demonstrates the possibility of a definitive diagnosis by FNAB prior to death without inflicting serious complications. PMID- 1638940 TI - Breast filariasis diagnosed by needle aspiration cytology. AB - A case of nodular lesion of the breast in a 37 year old female caused by filariasis is described. The case is instructive since the diagnosis was made by fine-needle aspiration cytology. PMID- 1638941 TI - Cerebrospinal fluid cytology: selected issues. PMID- 1638942 TI - Nodular goiter: a histo-cytological study with some emphasis on pitfalls of fine needle aspiration cytology. AB - A comprehensive comparative histo-cytological study of 48 nodular goiters from an endemic goiter region was undertaken. Practically all features observed on the biopsies were identified, although with less frequency, on the smears. In agreement with previous observations, characteristic components of nodular goiter (NG) in aspirates included small to medium size epithelial cells with regular round nuclei, honeycomb pattern, large follicles, papillae showing the previously mentioned epithelial features, oxyphilic cells, and moderate to abundant background colloid material and thyroid phagocytes (macrophages). All eight features occurred together in only 2% of the studied cases, seven in 6 (12.5%), six in 4 (8%), five in 6 (12.5%), four in 12 (25%), three in 6 (12.5%), two in 11 (23%), and one in 2 (4%) cases, respectively. Regardless of the number and combination of features present, specific identification of NG on the smears may not always be possible and diagnostic pitfalls include thyroid cyst, Hashimoto's thyroiditis, granulomatous lesions, and, more frequently, follicular neoplasia. Our findings suggest that thyroid aspirates should be analysed with critical clinico-pathological approach and surgery considered only for nodules that are clinically suspicious or unresponsive to hormonotherapy when a diagnosis of follicular neoplasia is made. PMID- 1638943 TI - Evaluation of cytocentrifuge apparatus with special reference to the cellular recovery rate. AB - Two types of commercially available cytocentrifuge apparatus (type A and type B apparatus) using disposable funnels were compared for percentage of cell recovery and degree of cell preservation. The cellularity of each cell suspension was determined using a Sysmex micro cell counter for blood analysis, and the cell recovery was obtained by counting cells in the total smeared area on the May Grunwald Giemsa (MGG)-stained slide. Overall recovery rate by the type A apparatus was between 54.3% and 74.9% with a mean of 63.0%, whereas, the recovery rate for type B apparatus was between 30.6% and 51.8%, with a mean of 42.5%, indicating that the type A apparatus was significantly better. In the type A apparatus, a higher yield of all cells was obtained (69.7-74.9%) in the group of low cell counts (350 cells/0.5 ml), which was run for 10 minutes at 2,000 rpm. On the other hand, in the type B apparatus a higher yield of all cells was obtained (38.6-42.6%) in the group of low cell counts which was run for 10 minutes at 2,000 rpm. Cellular structure was better preserved on the slides in the type A apparatus. However, the percentage of ghost cells was somewhat higher in the type B apparatus. The cytocentrifugation of the type A apparatus consistently recovered a higher percentage of cells than with the type B apparatus. Using the type A apparatus, a high rate of cellular recovery, which is extremely important, such as for accurate morphological evaluation of cerebrospinal fluid, can be consistently obtained. PMID- 1638944 TI - New technique for cell block preparation after fine-needle aspiration of breast lumps. PMID- 1638946 TI - Cytopathology in Egypt. PMID- 1638945 TI - Protoplasmic astrocytoma: cytologic features on tissue imprint preparation. PMID- 1638947 TI - [Mimicry of gastrointestinal regulator peptides in human immunodeficiency virus gp120 and gp41 [correction of gp40] proteins as a possible factor of its tissue polytropism]. PMID- 1638948 TI - [Psychotropic properties of brain proline endopeptidase inhibitors]. PMID- 1638949 TI - [Bent DNA in the area of the replication initiation domain of chicken alpha globin genes]. PMID- 1638950 TI - [The connection between DNA topology and acetylation of histones]. PMID- 1638951 TI - [Perception of low intensity electromagnetic radiation in the millimeter range by skate electrical receptors]. PMID- 1638952 TI - [Analysis of the distribution of actin filaments in rat large intestine enterocytes during nutrient absorption. An immunoelectron microscopic study)]. PMID- 1638953 TI - [Light sensitivity of human vision during change of position of the eye in the orbit]. PMID- 1638954 TI - [Asymmetry of phenotypical and functional properties of lymphoid organ cells]. PMID- 1638955 TI - [Cobalt and immunogenesis in birds (using domestic chickens as an example)]. PMID- 1638956 TI - [Hepatocytes, stimulated to proliferation in vivo, induce DNA synthesis in nuclei of resting fibroblasts in heterokaryons]. PMID- 1638957 TI - [NMR spectroscopy of tumors. Effects of subpopulation replacement in a growing tumor]. PMID- 1638958 TI - [Structural analysis of a protein component from black widow spider venom, interacting with alpha-latrotoxin]. PMID- 1638959 TI - [Spinal muscle atrophy in Brown Swiss x Braunvieh cross calves]. AB - The report describes seven SMA-cases in descendents of crossbreeds of American Brown Swiss x Deutsches Braunvieh. Symptoms and course: After initially normal development of the calves for one to six weeks the disease set in suddenly followed by a rapid lethal course of one to one and a half weeks duration due to asphyxia and/or secondary diseases. Only one case was reported having been sick since birth (?). Characteristic signs were rapidly progressing muscular atrophy, paresis and paralysis of the limbs, the trunk and the diaphragm, usually accompanied by progressive dyspnoea. Signs of congenital neuromyodysplasia (arthrogryposis) of different degree were present in four of the seven calves. Six calves had contracted a secondary pneumonia. Blood gas analysis (6/7) revealed a compensated (1x) or decompensated (4x) respiratory acidosis. Neurohistological findings: Degeneration and loss of motor neurons in the ventral horns of the spinal cord and neurogenic muscular atrophy. Immunohistochemistry revealed a pronounced accumulation of type 200 kD-neurofilaments in perikarya and dendrites of ventral horn motoneurons indicating disturbed mechanisms of the axonal transport. The disease seems to be inherited as a recessive trait. PMID- 1638960 TI - Abnormal ruminal digestion in cattle with dominantly non-digestive disorders. AB - Health disturbances of ruminal origin in cattle are summed up. The problems are classified in those caused by special feed (NPN for example), those caused by insufficient ruminal detoxication capacity (poisoning by nitrate or aliphatic N derivates) and belonging to ruminal toxin production (3-methyl-indole, S-methyl cysteine-sulfoxide, glucosinolates) and arranged in pathophysiological sense. PMID- 1638961 TI - [Dynamics of the acid-base balance of venous and arterial blood in clinically healthy calves]. AB - Values of the acid base balance were examined in both venous and arterial blood of healthy calves (n = 6) of the Slovak Spotted breed aged, 3, 6, 8, 10, 12, 14, 18, and 24 weeks, respectively. Until week 4 of age the animals were fed milk only, until the age of 9 weeks a milk-roughage transition fodder and from week 10 on they were given classical herbage. Blood samples were taken from the V. jugularis and A. carotis communis or A. axillaris, respectively. The results achieved were corrected to a body temperature of 39 degrees C. During the examination period the following values were stated for both arterial and venous blood: actual acidity (pH) 7.391 +/- 0.014 and 7.362 +/- 0.013 logmolc, pCO2 6.35 +/- 0.15 and 7.35 +/- 0.11 kPa, HCO3-28.38 +/- 1.42 and 30.32 +/- 1.02 mmol. l( 1), ABE 3.57 +/- 1.44 and 4.34 +/- 1.09 mmol. l(-1); pO2 12.63 +/- 1.15 and 5.21 +/- 0.73 kPa, SAT 95.8 +/- 1.03 and 61.2 +/- 9.59%, respectively. A gradual increase in most indices of the acid base balance could be stated both in arterial and venous blood. The trends either revealed a parallel increase (HCO3-, pH) or they were more pronounced either in venous blood (SAT) or in arterial blood (ABE, pO2). Some trends were almost balanced (pCO2 and pO2 in venous blood and SAT and pCO2 in arterial blood). Thus pH, pO2 and SAT indices of the acid base balance were higher in arterial blood as compared to venous blood while pCO2, HCO3- and ABE values were higher in venous blood.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1638962 TI - Epizootic botulism of cattle in Brazil. AB - The first diagnosis of botulism in cattle in Brazil and its epizootiology are reviewed. The high prevalence of the disease raised on phosphorus deficient pastures in Savanna regions has caused severe economic losses in the past. The temperature induced microcomplement fixation test (TIMCF) confirmed the clinical pathological diagnosis in all of the 24 cases studied by this method. The most important reason why botulism has not been controlled satisfactorily in Brazil is the lack of an available effective vaccine (type C and D). Additional prophylactic measures are phosphorus supplementation and removal of carcasses from the pasture. PMID- 1638963 TI - [The effect of technopathologically limited stress factors on the fertility of cattle]. AB - The influence of purulent claw-diseases on the development of uterus infections, its involution and ovary dysfunctions (acyclia, cysts) was examined. It was shown that A. pyogenes, Ps. aeruginosa, Fus. necrophorum and other microorganisms involved in these lesions are potential sources for the infections of the uterus. In comparison with the controls the frequency of endometritis was twice in the group with claw-problems. Similar differences existed in the involution-time of the uterus or its atonia, acyclia and the development of ovarian cysts (p less than 0.01). The Index of insemination was elevated by about 65%. PMID- 1638964 TI - [Clinical forms of enzootic pneumonia in calves and their effects on respiration]. AB - Enzootic pneumonia was diagnosed in 160 of 225 bullocks in a livestock fattening unit. Within the first 10 weeks, 51 of those affected contracted the disease a second time after the symptoms had vanished. Acute catarrhal bronchopneumonia were most common (49.3%) during the first outbreak, whereas acute catarrhal purulent bronchopneumonia (39.2%) and chronic pneumonia (29.4%) were most common during the second. Arterial blood gas analysis was undertaken for 33 clinically healthy bullocks and 100 bullocks with clinically diagnosed acute bronchitis, acute catarrhal bronchopneumonia, acute catarrhal purulent bronchopneumonia and chronic pneumonia. The pO2, SATO2 and A-aDO2 levels found in blood from the abdominal aorta of all diseased animals differed significantly from those of healthy animals. The values for animals with distinct catarrhal bronchopneumonia and catarrhal purulent bronchopneumonia showed the greatest differences. PMID- 1638965 TI - [Results of experimental immunization of calves with different Pasteurella antigens]. AB - Calves immunised with different Pasteurella antigens (inactivated whole cells, sodium chloride extract) where challenged two weeks after the second immunization with the homologous strain. The intracutaneous application of whole cells of P. haemolytica A1 and P. multocida A was effective. The incidence of pneumonia was reduced and the pneumonic lesions were less severe. The sodium chloride extract was not effective. PMID- 1638966 TI - Ki-67 antigen expression in lymphocytes of cattle infected with bovine leukemia virus (BLV). AB - The Ki-67 monoclonal antibody, which recognizes an antigen present on the nuclear membrane surface of mammalian cells in the replication phase, has been used for the determination of the cellular cycle of peripheral blood lymphocytes on a group of cattle positive for bovine leukemia virus (BLV) and with blood values showing a persistent lymphocytosis. The results obtained have shown that: 1. Both of the techniques used (immunofluorescence and immunoperoxidase) are easily applicable and give uniform results; 2. Cattle with a persistent lymphocytosis show an absolute number of cells in cycle significantly more elevated compared with cattle positive for BLV with normal blood values. PMID- 1638967 TI - [A new treatment for trichophytosis of cattle]. AB - A new way to treat ringworm in calves and young cattle giving 1 ml formaldehyde solution (10%) per kg BW intravenously is described. PMID- 1638968 TI - [The effect of the lactation period on the cell content of sheep milk]. AB - Milk samples of 201 ewes were examined in 6 week intervals during a complete lactation period. Those samples were analyzed for the presence of pathogenic bacteria and the somatic cell count was determined. Besides, the California Mastitis Test (CMT) was performed and the udder was clinically examined. The cell counts were found to depend on the lactation period. During 6 weeks following parturition the cell count was 63,000 cells/ml. This number decreased towards the 24th week of lactation to 32,000 cells/ml. At the end of lactation this value increased again to 425,000 cells/ml. The median value of ewes with normal udder health was 56,000 cells/ml milk. For samples from which pathogenic bacteria were isolated this value was 159,000 cells/ml. The most frequent pathogens isolated from the milk samples were coagulase-negative cocci (59.6% of bacteriologically positive samples), the median number being 88,000 somatic cells/ml in these sheep. Coagulase-positive cocci were isolated in 25.3% of the samples, the median value of the cell count was 295,000 cells/ml. In 12.1% of the samples streptococci were found. The median value was 167,000 cells/ml. From the remaining 3.0% of bacteriologically positive samples Pasteurellae, E. coli and Actinomycetae were isolated. The median value of the somatic cell count was 184,000 cells/ml. We consider coagulase-positive cocci therefore as the most pathogenic bacteria for the ovine udder. PMID- 1638969 TI - [The effect of seasonal undernutrition on the protein fractions in the blood of Moroccan cattle]. AB - In a trial including 84 cattle from three farms near Rabat (Morocco) the influence of undernutrition (dry season September to February) on the concentration of total protein and its fractions in the blood of cattle was investigated. The results out of the field were confirmed by comparing these concentrations during an experimental cycle of sufficient--insufficient- sufficient feed. It was obvious that malnutrition decreases the concentration of total protein and some of its fractions (albumins, gamma-globulins) in the blood by about 10%, while alpha- and beta-globulins remained nearly uneffected. PMID- 1638970 TI - [BVD/MD and its control in Lower Saxony (after the support of the Lower Saxony animal epidemic fund)]. AB - A report is given on the development of the subsidies granted by the "Niedersachsische Tierseuchenkasse" fur BVD/MD since 1973. The article shows the cyclic procedure and regional differences as well as the participation of vaccinations and embryo transfer at the frequent occurrence of persistent viraemic animals in single herds. According to the authors' opinion the struggle against BVD/MD must have two aims: 1. to search for and to cull out persistent viraemic animals 2. to prevent the arise of new persistent viraemic animals. PMID- 1638971 TI - [The effect of energy-rich feed supplements for cows on the health of their calves]. AB - Experiments were carried out with 24 pregnant cows and their calves. The cows were divided in 2 equal groups. One of these received a supplement of animal fat additional to the feed from 4 weeks a. p. to 6 weeks p. p. Apart from clinical examinations following laboratory investigations in the blood were performed: hematological parameters, cholesterol, lipids, free fatty acids, ketone bodies, protein, glucose, bilirubin, transaminases, alkaline phosphatase, Ca, Mg, P, K, Na, Cl. The addition of fat to the feed of cows influenced the energy metabolism of the cows, the body weight of the newborn ones and some hematological parameters (incl. protein) of the calves positively. PMID- 1638972 TI - [Elimination kinetics of several clinically relevant enzymes in the blood plasma of cattle after intravenous bolus infusion of homologous preparations]. AB - Extracts of homologous organs (liver, muscle) and of colostrum were infused intravenously in cattle of two different age groups: heifers (n = 9, each preparation was infused in 3 animals) and calves (n = 6, preparations from liver and muscle were infused in 3 animals each). Parameters of elimination kinetics were determined for some clinically relevant enzymes. Enzyme elimination was quicker in the younger animals. The volume of enzyme distribution was comparable to plasma volume. Biological half-lives in calves and heifers respectively were: CK from muscle 3.46 +/- 0.65 h and 8.27 +/- 3.27 h, AST from muscle 9.74 +/- 1.38 h and 33.48 +/- 3.74 h, AST from liver 14.99 +/- 0.81 h and 16.71 +/- 0.58 h, GLDH from liver 14.61 +/- 1.88 h and 25.09 +/- 4.13 h, SDH from liver 13.95 +/- 2.25 h and 17.68 +/- 0.81 h, GGT from colostrum 1.69 +/- 0.95 h (only heifers). PMID- 1638973 TI - [The composition of rumen fluid of cattle collected from fistulas using ultrasound]. AB - Concentrations of rumen fluid characteristics were compared between rumen fluid which was taken by standardized conditions via stomach tube and via rumen fistula respectively depending on time after feeding (2.5 or 9 hours ppr.). The results were as follows: Differences (%) of the characteristics of rumen fluid taken via stomach tube to that by rumen fistula: [table: see text] Other investigations showed that the admixture of saliva to rumen fluid resulted in a degradation of the concentrations especially of VFA. The pH was not appreciable changed. The consequences for veterinary practitioners are discussed. PMID- 1638974 TI - Cytoplasmic and cortical determinants interact to specify ectoderm and mesoderm in the leech embryo. AB - In leech embryos, segmental ectoderm and mesoderm are produced by a pair of sister cells located near the animal and vegetal poles, respectively. We have investigated the mechanism that localizes ectodermal and mesodermal fates along the animal-vegetal axis. The results of cleavage arrest and cell ablation experiments suggest that the full range of normal cell interactions are not required for this process. However, when the animal and vegetal hemispheres are separated by re-orientation of the first cleavage plane from meridional to equatorial, the ectodermal fate co-segregates with the animal hemisphere and the mesodermal fate with the vegetal hemisphere. Two pools of yolk-deficient cytoplasm, called teloplasm, are located at the animal and vegetal poles of the zygote, but separation of the animal and vegetal teloplasms is not sufficient for the segregation of ectodermal and mesodermal fates. Rather, complete segregation of fates requires an equatorial cleavage orientation that separates not only the two teloplasms, but also the animal and vegetal cortical regions. This, in conjunction with previous findings, indicates that ectodermal determinants are localized to the cell cortex in the animal hemisphere of the zygote. We propose that these determinants segregate to the ectodermal precursor and interact with factors in teloplasm to transform the fate of this cell from a mesodermal ground state to ectoderm. PMID- 1638975 TI - c-ros: the vertebrate homolog of the sevenless tyrosine kinase receptor is tightly regulated during organogenesis in mouse embryonic development. AB - The c-ros proto-oncogene is the vertebrate homologue of the Drosophila sevenless tyrosine kinase receptor. Examination of c-ros mRNA transcripts in the mouse embryo reveals a stringent pattern of expression. Only kidney, intestine and lung exhibit ros-specific RNA using sensitive techniques such as RNAase protection and in situ hybridization. The temporal and spatial arrangement of c-ros transcripts is coincident with the phenotypic induction and proliferation of epithelium during organogenesis of the kidney and intestine. The data provide evidence for a role of c-ros in the obligate cell-cell interactions that characterize the morphogenic induction and proliferation of epithelial cells in the kidney, intestine and lung. The c-ros tyrosine kinase receptor may provide a signal transduction pathway for epithelial-mesenchymal interactions. PMID- 1638976 TI - A PDGF receptor mutation in the mouse (Patch) perturbs the development of a non neuronal subset of neural crest-derived cells. AB - The Patch (Ph) mutation in mice is a deletion of the gene encoding the platelet derived growth factor receptor alpha subunit (PDGFR alpha). Patch is a recessive lethal recognized in heterozygotes by its effect on the pattern of neural crest derived pigment cells, and in homozygous mutant embryos by visible defects in craniofacial structures. Since both pigment cells and craniofacial structures are derived from the neural crest, we have examined the differentiation of other crest cell-derived structures in Ph/Ph mutants to assess which crest cell populations are adversely affected by this mutation. Defects were found in many structures populated by non-neuronal derivatives of cranial crest cells including the thymus, the outflow tract of the heart, cornea, and teeth. In contrast, crest derived neurons in both the head and trunk appeared normal. The expression pattern of PDGFR alpha mRNA was determined in normal embryos and was compared with the defects present in Ph/Ph embryos. PDGFR alpha mRNA was expressed at high levels in the non-neuronal derivatives of the cranial neural crest but was not detected in the crest cell neuronal derivatives. These results suggest that functional PDGF alpha is required for the normal development of many non-neuronal crest-derived structures but not for the development of crest-derived neuronal structures. Abnormal development of the non-neuronal crest cells in Ph/Ph embryos was also correlated with an increase in the diameter of the proteoglycan containing granules within the crest cell migratory spaces. This change in matrix structure was observed both before and after crest cells had entered these spaces. Taken together, these observations suggest that functional PDGFR alpha can affect crest development both directly, by acting as a cell growth and/or survival stimulus for populations of non-neurogenic crest cells, and indirectly, by affecting the structure of the matrix environment through which such cells move. PMID- 1638978 TI - Demonstration of a phagocytic cell system belonging to the hemopoietic lineage and originating from the yolk sac in the early avian embryo. AB - It is well established that hemopoietic cells arising from the yolk sac invade the avian embryo. To study the fate and role of these cells during the first 2.5 4.5 days of incubation, we constructed yolk sac chimeras (a chick embryo grafted on a quail yolk sac and vice versa) and immunostained them with antibodies specific to cells of quail hemangioblastic lineage (MB1 and QH1). This approach revealed that endothelial cells of the embryonic vessels are of intraembryonic origin. In contrast, numerous hemopoietic cells of yolk sac origin were seen in embryos ranging from 2.5 to 4.5 days of incubation. These cells were already present within the vessels and in the mesenchyme at the earliest developmental stages analyzed. Two hemopoietic cell types of yolk sac origin were distinguishable, undifferentiated cells and macrophage-like cells. The number of the latter cells increased progressively as development proceeded, and they showed marked acid phosphatase activity and phagocytic capacity, as revealed by the presence of numerous phagocytic inclusions in their cytoplasm. The macrophage like cells were mostly distributed in the mesenchyme and also appeared within some organ primordia such as the neural tube, the liver anlage and the nephric rudiment. Comparison of the results in the two types of chimeras and the findings obtained with acid phosphatase/MB1 double labelling showed that some hemopoietic macrophage-like cells of intraembryonic origin were also present at the stages considered. These results support the existence in the early avian embryo of a phagocytic cell system of blood cell lineage, derived chiefly from the yolk sac. Cells belonging to this system perform phagocytosis in cell death and may also be involved in other morphogenetic processes. PMID- 1638977 TI - Expression of the L14 lectin during mouse embryogenesis suggests multiple roles during pre- and post-implantation development. AB - A cDNA encoding L14, the lactose-binding, soluble lectin of relative molecular mass 14 x 10(3), has been isolated in a differential screen designed to identify genes that are regulated during the differentiation of murine embryonic stem cells in vitro. The expression patterns of the gene and of the encoded protein during mouse embryogenesis are consistent with the lectin playing a role at several stages of development. Firstly, it is initially synthesised in the trophectoderm of expanded blastocysts immediately prior to implantation, suggesting that it may be involved in the attachment of the embryo to the uterine epithelium. Secondly, in the postimplantation embryo, the lectin is abundantly expressed in the myotomes of the somites. This observation, when taken together with data indicating a role for the lectin in myoblast differentiation in culture, suggests that the protein is important in muscle cell differentiation. Finally, within the nervous system expression of this gene is activated early during the differentiation of a particular subset of neurones. PMID- 1638979 TI - Histone H1 subtype synthesis in neurons and neuroblasts. AB - Rat cerebral cortex neurons contain the five histone H1 subtypes H1a-e and the subtype H1 zero present in other mammalian somatic tissues. The four subtypes H1a d decay exponentially during postnatal development and are partially or totally replaced by H1e that becomes the major H1 subtype in adults. H1 zero accumulates in a period restricted to neuronal terminal differentiation. Here we study the synthesis of the H1 subtypes in cortical neurons and their neuroblasts by in vivo labeling with [14C]lysine. The subtype synthesis pattern of neuroblasts has been determined by labeling gravid rats during the period of proliferation of cortical neurons and synthesis in neurons has been studied by postnatal labeling. The subtype H1a is synthesized in neuroblasts but not in neurons and is therefore rapidly removed from neuronal chromatin. The synthesis of H1b and H1d is much lower in neurons than in neuroblasts so that these subtypes are replaced to a large extent during postnatal development. H1c is synthesized at levels much higher than the other subtypes both in neurons and neuroblasts, but its very high turnover, about one order of magnitude faster than that of H1e in neurons, favors its partial replacement during postnatal development. Comparison of the synthesis rates of H1 zero in newborn and 30-day-old rats shows that the accumulation of H1 zero in differentiating neurons is due to an increased level of synthesis. PMID- 1638981 TI - A 102 base pair sequence of the nicotinic acetylcholine receptor delta-subunit gene confers regulation by muscle electrical activity. AB - Muscle electrical activity suppresses expression of the embryonic-type (alpha, beta, gamma, and delta) nicotinic acetylcholine receptor (nAChR) genes. The molecular mechanism by which electrical activity regulates these genes is not known. One approach to this problem is to identify regions of the nAChR genes that mediate electrical regulation. Here we report results from such a study of the nAChR delta-subunit gene. We cloned the rat delta-subunit promoter region and created an expression vector in which this DNA controlled the expression of a down-stream luciferase structural gene. The effect that muscle electrical activity had on the expression from this promoter was assayed by introducing this expression vector into electrically stimulated and tetrodotoxin (TTX)-treated rat primary myotubes, and assaying for luciferase activity. These myotubes, when stimulated with extracellular electrodes, suppressed endogenous embryonic-type nAChR gene expression compared to those treated with TTX. Transfection of these cells with delta-promoter-luciferase expression vectors resulted in the delta promoter conferring electrical regulation on luciferase expression. Additional experiments using deletions from the 5' end of the delta-promoter region have identified an element between -677 and -550 bp that suppressed delta-promoter activity and a minimal 102 bp sequence that promotes and regulates luciferase expression in response to muscle electrical activity. This latter sequence also contains all the necessary elements to confer tissue and developmental stage specific expression. PMID- 1638980 TI - Developmentally regulated expression of alpha 6 integrin in avian embryos. AB - The distribution pattern of the avian alpha 6 integrin subunit was examined during early stages of development. The results show that this subunit is prevalent in cells of the developing nervous system and muscle. alpha 6 is first observed on neuroepithelial cells of the cranial neural plate and trunk neural tube. With time, immunoreactivity becomes prominent near the lumen and ventrolateral portions of the neural tube, co-distributing with neurons and axons, particularly notable on commissural neurons. The alpha 6 expression pattern is dynamic in the neural tube, with immunoreactivity peaking by embryonic day 6 (stage 30) and decreasing thereafter. The ventral roots and retina exhibit high levels of immunoreactivity throughout development. In the peripheral nervous system, alpha 6 immunoreactivity first appears on a subpopulation of sympathoadrenal cells around the dorsal aorta and later in the dorsal root ganglia shortly after gangliogenesis. Immunoreactivity appears on prospective myotomal cells as the somites delaminate into the dermomyotome and sclerotome, remaining prominent on myoblasts and differentiated muscle at all stages. The mesonephros also has intense immunoreactivity. In the periphery, alpha 6 immunoreactive regions often in proximity to laminin, which is thought to be the ligand of alpha 6 beta 1 integrin. PMID- 1638982 TI - Polarity of the ascidian egg cortex before fertilization. AB - The unfertilized ascidian egg displays a visible polar organization along its animal-vegetal axis. In particular, the myoplasm, a mitochondria-rich subcortical domain inherited by the blastomeres that differentiate into muscle cells, is mainly situated in the vegetal hemisphere. We show that, in the unfertilized egg, this vegetal domain is enriched in actin and microfilaments and excludes microtubules. This polar distribution of microfilaments and microtubules persists in isolated cortices prepared by shearing eggs attached to a polylysine-coated surface. The isolated cortex is further characterized by an elaborate network of tubules and sheets of endoplasmic reticulum (ER). This cortical ER network is tethered to the plasma membrane at discrete sites, is covered with ribosomes and contains a calsequestrin-like protein. Interestingly, this ER network is distributed in a polar fashion along the animal-vegetal axis of the egg: regions with a dense network consisting mainly of sheets or tightly knit tubes are present in the vegetal hemisphere only, whereas areas characterized by a sparse tubular ER network are uniquely found in the animal hemisphere region. The stability of the polar organization of the cortex was studied by perturbing the distribution of organelles in the egg and depolymerizing microfilaments and microtubules. The polar organization of the cortical ER network persists after treatment of eggs with nocodazole, but is disrupted by treatment with cytochalasin B. In addition, we show that centrifugal forces that displace the cytoplasmic organelles do not alter the appearance and polar organization of the isolated egg cortex. These findings taken together with our previous work suggest that the intrinsic polar distribution of cortical membranous and cytoskeletal components along the animal-vegetal axis of the egg are important for the spatial organization of calcium-dependent events and their developmental consequences. PMID- 1638983 TI - bicoid and the terminal system activate tailless expression in the early Drosophila embryo. AB - In the early Drosophila embryo, the maternal terminal genes are required for formation of the acron at the anterior and the telson at the posterior. We show here that the terminal system, a signal transduction pathway active at the poles of the embryo, is required to activate transcription of the key zygotic gene tailless (tll) in two symmetrical domains. Consistent with the characterization of the tll protein as a putative transcription factor (a member of the steroid receptor superfamily) that represses segmentation genes and activates terminal specific genes, we observe a correlation between the presence of the posterior cap of tll expression and differentiation of a telson. While the maternal patterning systems of the Drosophila embryo function for the most part independently, the maternal anterior system, in which the bicoid (bcd) protein functions as a graded morphogen, is required together with the terminal system to establish the acron. This dual requirement is evident at the molecular level in the control of tll expression. We find that bcd and the terminal system are required together to activate the anterior-dorsal stripe of tll expression that is correlated with formation of the acron. In the absence of bcd, the anterior cap of tll expression established by the terminal system persists and an ectopic telson forms at the anterior, while in the absence of terminal system activity only an abnormal anterior stripe forms. This is the first described example of how, by jointly controlling expression of the same gene, two systems of positional information function together to set unique positional values. PMID- 1638984 TI - Control of proliferation in the retina: temporal changes in responsiveness to FGF and TGF alpha. AB - Proliferation in the rat retina, as in other parts of the nervous system, occurs during a restricted period of development. In addition to regulating cell number, the mechanisms that control proliferation influence the patterning of tissues, and may affect the determination of cell type. To begin to determine how proliferation is controlled, several growth factors found in the retina were tested for effects on progenitor cell division in culture. Proliferation was enhanced by TGF alpha, bFGF and aFGF, and many of the dividing cells later differentiated into cells with the antigenic phenotypes of retinal neurons and glial cells. The mitotic response of retinal cells to these factors changed during development: progenitor cells from younger retinas (embryonic day 15 to 18; E15-E18) were more responsive to FGF's, while progenitor cells from older retinas (greater than E20) were more responsive to TGF alpha. Progenitor cells stopped dividing in vitro, even when treated with excess mitogen. These observations suggest that proliferation in the retina may be stimulated by multiple mitogenic signals provided by TGF alpha, FGF, or related factors, and that proliferation is not controlled by limiting concentrations of mitogen alone. Rather, these data demonstrate that retinal cells change during development in their responsiveness to mitogenic signals. Such changes may contribute to the regulation of proliferation. PMID- 1638985 TI - Dynamic expression of the cell adhesion molecule fasciclin I during embryonic development in Drosophila. AB - A number of different cell surface glycoproteins expressed in the central nervous system (CNS) have been identified in insects and shown to mediate cell adhesion in tissue culture systems. The fasciclin I protein is expressed on a subset of CNS axon pathways in both grasshopper and Drosophila. It consists of four homologous 150-amino acid domains which are unrelated to other sequences in the current databases, and is tethered to the cell surface by a glycosyl phosphatidylinositol linkage. In this paper we examine in detail the expression of fasciclin I mRNA and protein during Drosophila embryonic development. We find that fasciclin I is expressed in several distinct patterns at different stages of development. In blastoderm embryos it is briefly localized in a graded pattern. During the germ band extended period its expression evolves through two distinct phases. Fasciclin I mRNA and protein are initially localized in a 14-stripe pattern which corresponds to segmentally repeated patches of neuroepithelial cells and neuroblasts. Expression then becomes confined to CNS and peripheral sensory (PNS) neurons. Fasciclin I is expressed on all PNS neurons, and this expression is stably maintained for several hours. In the CNS, fasciclin I is initially expressed on all commissural axons, but then becomes restricted to specific axon bundles. The early commissural expression pattern is not observed in grasshopper embryos, but the later bundle-specific pattern is very similar to that seen in grasshopper. The existence of an initial phase of expression on all commissural bundles helps to explain the loss-of-commissures phenotype of embryos lacking expression of both fasciclin I and of the D-abl tyrosine kinase. Fasciclin I is also expressed in several nonneural tissues in the embryo. PMID- 1638986 TI - Identification and characterization of a novel, evolutionarily conserved gene disrupted by the murine H beta 58 embryonic lethal transgene insertion. AB - The H beta 58 transgenic mouse line carries a recessive insertional mutation that results in developmental abnormalities beginning at day 7.5 p.c. and embryonic arrest at about day 9.5. In this paper, we describe the characterization of a novel gene encoded at the H beta 58 locus, whose disruption appears to be responsible for the mutant phenotype. The wild-type H beta 58 gene encodes a single 2.7 kb mRNA during embryonic and fetal development, and in many adult somatic tissues. In the mutant locus, this transcription unit is split by the transgene insertion, and one of its coding exons is deleted. Consistent with the physical disruption of the gene, the level of the H beta 58 mRNA in heterozygous mutant mouse tissues was half the normal level, indicating that the mutant allele fails to encode a stable mRNA. In situ hybridization studies revealed that expression of the wild-type H beta 58 gene begins in the oocyte, and continues throughout pre- and post-implantation embryogenesis, despite the fact that homozygous mutant embryos develop successfully through the egg cylinder stage (day 6.5 p.c.). In the early post-implantation embryo, expression of the normal H beta 58 gene is relatively low in the embryonic ectoderm, the tissue displaying the earliest phenotypic effects of the mutation, and highest in the visceral endoderm. We therefore propose that the effects of the mutation on the embryonic ectoderm may be exerted indirectly, via the visceral endoderm. Sequence analysis of H beta 58 cDNA clones revealed no homology between the 38 x 10(3) M(r) H beta 58 protein and other known proteins. However, the H beta 58 gene displayed extremely strong conservation between mammals and birds (greater than 96% amino acid identity), although it appeared less conserved in amphibians and invertebrates. PMID- 1638987 TI - Developmental expression and cellular localization of glucose transporter molecules during mouse preimplantation development. AB - Two general mechanisms mediate glucose transport, one is a sodium-coupled glucose transporter found in the apical border of intestinal and kidney epithelia, while the other is a sodium-independent transport system. Of the latter, several facilitated transporters have been identified, including GLUT1 (erythrocyte/brain), GLUT2 (liver) and GLUT4 (adipose/muscle) isoforms. In this study, we used Western-blot analysis and high resolution immunoelectron microscopy (IEM) to investigate the stage-related expression and cellular localization of GLUT1, 2 and 4. The Western blot results demonstrate that GLUT1 is detectable in the oocyte and throughout preimplantation development. GLUT2 isoforms were not detectable until the blastocyst stage, while the GLUT4 isoform was undetectable in the oocyte through blastocyst stages. The present findings confirm previous studies at the molecular level which demonstrated that mRNAs encoding the same GLUT isoforms are detectable at corresponding developmental stages. GLUT1 and GLUT2 display different cellular distributions at the blastocyst stage as shown by IEM studies. GLUT1 has a widespread distribution in both trophectoderm and inner cell mass cells, while GLUT2 is located on trophectoderm membranes facing the blastocyst cavity. This observation suggests a different functional significance for these isoforms during mouse preimplantation development. PMID- 1638988 TI - Synthesis and phosphorylation of uvomorulin during mouse early development. AB - The cell adhesion molecule, uvomorulin, is synthesised in both the 135 x 10(3) M(r) precursor and 120 x 10(3) M(r) mature forms on maternal mRNA templates in unfertilized and newly fertilized mouse oocytes. Synthesis on maternal message ceases during the 2-cell stage to resume later on mRNA encoded presumptively by the embryonic genome. Uvomorulin is detectable by immunoblotting at all stages upto the blastocyst stage, but shows variations in its total amount and processing with embryonic stage. Whilst only trace levels of phosphorylated uvomorulin are detectable in early and late 4-cell embryos, uvomorulin in 8-cell embryos is phosphorylated. PMID- 1638989 TI - Development of surface pattern during division in Paramecium. II. Defective spatial control in the mutant kin241. AB - kin241 is a monogenic nuclear recessive mutation producing highly pleiotropic effects on cell size and shape, generation time, thermosensitivity, nuclear reorganization and cortical organization. We have analyzed the nature of the cortical disorders and their development during division, using various specific antibodies labelling either one of the cortical cytoskeleton components, as was previously done for analysis of cortical pattern formation in the wild type. Several abnormalities in basal body properties were consistently observed, although with a variable frequency: extra microtubules in either the triplets or in the lumen; nucleation of a second kinetodesmal fiber; abnormal orientation of the newly formed basal body with respect to the mother one. The latter effect seems to account for the major observed cortical disorders (reversal, intercalation of supplementary ciliary rows). The second major effect of the mutation concerns the spatiotemporal map of cortical reorganization during division. Excess basal body proliferation occurs and is correlated with modified boundaries of some of the cortical domains identified in the wild type on the basis of their basal body duplication pattern. This is the first mutant described in a ciliate in which both the structure and duplication of basal bodies and the body plan are affected. The data support the conclusion that the mutation does not alter the nature of the morphogenetic signal(s) which pervade the dividing cell, nor the competence of cytoskeletal structures to respond to signalling, but affects the local interpretation of the signals. PMID- 1638990 TI - Secretory and inductive properties of Drosophila wingless protein in Xenopus oocytes and embryos. AB - Like its vertebrate homologues, Xenopus wnt-8 and murine wnt-1, we find that Drosophila wingless (wg) protein causes axis duplication when overexpressed in embryos of Xenopus laevis after mRNA injection. In many cases, the secondary axes contain eyes and cement glands, which reflect the induction of the most dorsoanterior mesodermal type, prechordal mesoderm. We show that the extent of axis duplication is dependent on the embryonic site of expression, with ventral expression leading to a more posterior point of axis bifurcation. The observed duplications are due to de novo generation of new axes as shown by rescue of UV irradiated embryos. The true dorsal mesoderm-inducing properties of wg protein are indicated by its ability to generate extensive duplications after mRNA injection into D-tier cells of 32-cell embryos. As revealed by lineage mapping, the majority of these D cell progeny populate the endoderm; injections into animal blastomeres at this stage are far less effective in inducing secondary axes. However, when expressed in isolated animal cap explants, wg protein induces only ventral mesoderm, unless basic fibroblast growth factor is added, whereupon induction of muscle and occasionally notochord is seen. We conclude that in intact embryos, wg acts in concert with other factors to cause axis duplication. Immunolocalisation studies in embryos indicate that wg protein remains localised to the blastomeres synthesizing it and has a patchy, often perinuclear distribution within these cells, although some gets to the surface. In oocytes, the pool of wg protein is entirely intracellular and relatively unstable. When the polyanion suramin is added, most of the intracellular material is recovered in the external medium. PMID- 1638991 TI - Apoptotic cell death and tissue remodelling during mouse mammary gland involution. AB - During post-lactational mammary gland involution, the bulk of mammary epithelium dies and is reabsorbed. This massive cell death and tissue restructuring was found to be accompanied by a specific pattern of gene expression. Northern blot analysis showed that weaning resulted in a dramatic drop in ODC, a gene involved in synthesis of a component of milk, and the nearly simultaneous induction of SGP 2, a gene associated with apoptotic cell death. These changes were followed by decreases in expression of milk protein genes to basal levels and expression of genes associated with regulation of cell proliferation and differentiation, p53, c-myc and TGF-beta 1. Subsequently, additional genes implicated in stress response, tissue remodelling, and apoptotic cell death were transiently expressed, expression peaking at about 6 days post-weaning. A non-random degradation of DNA yielding the oligonucleosomal length fragmentation pattern typical of apoptotic cell death (Wyllie, 1980; Wyllie et al., 1980) was detected in association with morphological changes and gene expression. The correlations between: (a) changes in morphology, (b) pattern of gene expression and (c) changes in DNA integrity suggest that complementary programs for cell death and tissue remodelling direct post-lactational mammary gland involution. PMID- 1638992 TI - Establishment and maintenance of stable spatial patterns in lacZ fusion transformants of Polysphondylium pallidum. AB - Polysphondylium pallidum cells were transformed with a construct containing the Dictyostelium discoideum ecmA promoter fused to a lacZ reporter gene. Two stably transformed lines, one in which beta-galactosidase (beta-gal) is expressed in apical cells of the fruiting body (p63/2.1), and one in which it is expressed in basal cells (p63/D), have enabled us to infer how cells move during aggregation and culmination. Several types of cell movement proposed to occur during slime mold culmination, such as random cell mixing and global cell circulation, can be ruled out on the basis of our observations. Cells of the two transformant lines express beta-gal very early in development. In both cases, stained cells are randomly scattered in a starving population. By mid to late aggregation, characteristic spatial patterns emerge. Marked cells of p63/2.1 are found predominantly at tips of tight aggregates; those of p63/D accumulate at the periphery. These patterns are conserved throughout culmination, showing that marked cells maintain their relative positions within the multicellular mass following aggregation. Neither the apical nor the basal pattern appears to be regulated within the primary sorogen by de novo gene expression or by cell sorting as whorls are formed. However, marked cells within a whorl re-establish the original pattern in secondary sorogens. This must be achieved by cell migration, since beta-gal is not re-expressed. PMID- 1638993 TI - Interactions between retinoids and TGF beta s in mouse morphogenesis. AB - Using immunocytochemical methods we describe the distribution of different TGF beta isoforms and the effects of excess retinoic acid on their expression during early mouse embryogenesis (8 1/2 - 10 1/2 days of development). In normal embryos at 9 days, intracellular TGF beta 1 is expressed most intensely in neuroepithelium and cardiac myocardium whereas extracellular TGF beta 1 is expressed in mesenchymal cells and in the endocardium of the heart. At later stages, intracellular TGF beta 1 becomes very restricted to the myocardium and to a limited number of head mesenchymal cells; extracellular TGF beta 1 continues to be expressed widely in cells of mesenchymal origin, particularly in head and trunk mesenchyme, and also in endocardium. TGF beta 2 is widely expressed at all stages investigated while TGF beta 3 is not expressed strongly in any tissue at the stages examined. Exposure of early neural plate stage embryos to retinoic acid caused reduced expression of TGF beta 1 and TGF beta 2 proteins but had no effect on TGF beta 3. Intracellular TGF beta 1 expression was reduced in all tissues except in the myocardium, while extracellular TGF beta 1 was specifically reduced in neuroepithelium and cranial neural crest cells at early stages. TGF beta 2 was reduced in all embryonic tissues. The down-regulation of intracellular TGF beta 1 was observed up to 48 hours after initial exposure to retinoic acid while some down-regulation of TGF beta 2 was still seen up to 60 hours after initial exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1638994 TI - The Drosophila orb gene is predicted to encode sex-specific germline RNA-binding proteins and has localized transcripts in ovaries and early embryos. AB - We report the identification of a new gene, orb, which appears to be expressed only in the germline and encodes ovarian- and testis-specific transcripts. The predicted proteins contain two regions with similarity to the RRM family of RNA binding proteins but differ at their amino termini. In testes, orb RNA accumulates in the primary spermatocytes and at the caudal ends of the spermatid bundles. In ovaries, orb transcripts display an unusual spatial pattern of accumulation in the oocyte. Preferential accumulation in the oocyte of orb RNA is first detected in region 2 of the germarium and is dependent on Bicaudal-D and egalitarian. While in stage 7 egg chambers orb RNA is localized posteriorly in the oocyte, during stages 8-10 it is localized at the anterior of the oocyte, asymmetrically along the dorsal-ventral axis. In embryos the transcripts accumulate at the posterior end and are included in the pole cells. This pattern of localization and the similarity to RNA-binding proteins suggest that the orb gene product may mediate the localization of maternal RNAs during oogenesis and early embryogenesis. PMID- 1638995 TI - A unique mutation in the Enhancer of split gene complex affects the fates of the mystery cells in the developing Drosophila eye. AB - An unusual recessive allele of the Drosophila groucho gene, which encodes a transducin-like protein, affects the fates of specific cells in the eye disc. groucho is one of several transcription units in the Enhancer of split complex. Most groucho mutations are zygotic lethal due to the proliferation of embryonic neural cells at the expense of epidermal cells. In contrast, flies homozygous for the mutant allele described here, groBFP2, are viable but have abnormal eyes. The Drosophila compound eye is composed of several hundred identical facets, or ommatidia, each of which contains eight photoreceptor cells, R1-R8. In groBFP2 mutant retinas, most of the facets contain eight normally determined photoreceptor cells and one or two additional R-cells of the R3/4 subtype. The extra photoreceptors appear to arise from the mystery cells, which are part of the precluster that initiates the ommatidium, but do not normally become neurons. groBFP2 behaves as a partial loss-of-function mutant. Analysis of ommatidia mosaic for wild-type and groBFP2 mutant cells suggests that the focus of action of the groBFP2 mutation is outside of the photoreceptor cells. These results imply that one function of groucho is in a pathway whereby neuralization of the mystery cells is inhibited by other non-neural cells in the eye disc. In addition, determination of R3/4 photoreceptors usually requires contact with R2 and R5. Specification of the mystery cells as ectopic R3/4 subtype photoreceptors in groBFP2 mutant eye discs implies that induction by R2 or R5 is not absolutely necessary for R3/4 cell determination. PMID- 1638996 TI - [Towards a neurodevelopmental hypothesis in schizophrenia]. AB - Since the first designation by E. Bleuler, various etiopathogenic theories have been proposed in schizophrenia. The dopaminergic hyperactivity hypothesis remains the more valid one. Recently, a neurodevelopmental hypothesis has been suggested in schizophrenia. This hypothesis postulates an early disturbance in the development of central nervous system, mainly in the temporo-limbic areas. This disturbance is not secondary to a degenerative process. It may take place during the end of the second trimester of the pregnancy and be complete at the time of puberty. Genetic and environmental factors co-occur to explain these brains developmental disturbances. This hypothesis has been formulated according to a tremendous amount of various data obtained with different methodologies. Neuropathological techniques observed a reduction in the number of cells and cyto architectural anomalies in different brain areas such as hippocampus and para hippocampus gyrus. The lack of associated gliosis suggests an early phenomenon developing before birth. Structural brain abnormalities have been demonstrated using various neuroimaging techniques. Computed tomographic scanning and magnetic resonance imaging reveal structural anomalies such as ventricular dilatation, and positron emission tomography functional ones such as frontal hypometabolism. These results appear to be unrelated to the severity, the duration and the treatment of the disease. More informations are needed to eventually confirm this hypothesis. Clinical, cognitive and neuropsychological data have to be completed. Longitudinal studies are urgently needed using clinical, epidemiological, genetic and neuroimaging techniques. PMID- 1638997 TI - [Methodological obstacles encountered in the evaluation of psychotherapies of schizophrenic patients. A general review]. AB - Through a critical review of literature, authors suggest a methodological reflexion about problems in evaluation of effects of psychotherapies of schizophrenics, taking into account not only individual techniques but also institutional ones with psychotherapeutic orientations. Among the main difficulties are: evaluation with too much unspecific and over simplified criteria, for example criterium of rehospitalisation; lack of real comparability between groups, or techniques, and lack of validity of randomisation, still considered as a pawn of methodological rigour; diversity of levels of experience, and education of therapists, too unmatched model of functional organisation of the different centers, and in the same time too unequal recruitment of patients and at length of proposed therapeutic programs. Moreover, and even before these methodological bias, a more basic obstacle must be considered. It is the non opening of models to the falsification, denounced by Bignami as the impossible verification of the heuristic value of the proposed models, ie the impossible verification of the utility of the proposed programs for individual therapies of schizophrenics. PMID- 1638998 TI - [Behavior dyscontrol scale: validation and initial results]. AB - The numerous recent trials devoted to disruptive behavior disorders indicate the renewed interest of clinicians for these so-called dimensions and call for revision of the instruments with which they are evaluated. The present paper provides a brief review of the currently used scales for rating impulsivity. A new scale for evaluating the behavioural dyscontrol is proposed. The items of this scale are selected a priori according to clinical experience with patients suffering from lack of behavioural control. The Behaviour Dyscontrol Scale (BDS) includes, in the initial version, 4 parts. The first part concerns the generalized lack of control (G-BDS). This is a questionnaire of 24 items. The second part is constituted by a questionnaire which lists a number of specific behaviours where impulsivity has a central role (S-BDS). Part III is constituted with 4 Visual Analogue Scales for evaluating handicap linked to dyscontrol. Part IV is constituted by 3 Visual Analogue Scales concerning the physician global impression about the lack of general control in cognitions, emotions and behaviours. For validation, 166 patients (111 females and 55 males), either hospitalized or ambulatory, and 35 controls (16 females and 19 males) were included in this study. Mean age of patients was 38.5 (SD = 10.5) years. The patients population is subdivided in 4 subgroups, anxious, depressed, abusers and bulimics according to DSM III-R criteria. Patients and controls global scores were significantly different at the G-BDS (p less than 10(-4)) and not at S BDS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1638999 TI - [French translation of Schalling-Sifneos Personality Scale Revised and Beth Israel Questionnaire, 2 evaluation tools of alexithymia]. AB - The concept of alexithymia was first proposed in the 1960's by Sifneos and Nemiah to describe personality traits originally found in psychosomatic patients but which have since been found in other types of patients (alcoholics, drug addicts, traumatic stress disorder patients, sociopaths) as well as in the general population. Etymologically, alexithymia signifies: incapacity to speak one's emotions (from the Greek: a, lack; lexis, word; thymos, sentiments). Alexithymia is not the impossibility of feeling one's emotions, but rather the impossibility of associating them with corresponding mental representations and thus verbalizing them. Such patients tend to act out, to speak circumstantially, and to have difficulty in relationships. A neurophysiological substratum, the absence of connexions between the limbic system and the neo-cortical regions, has been suggested by Sifneos, who has distinguished primary and secondary alexithymia. A "biological" deficit seems to be responsible for primary alexithymia, such as in found in split-brain patients or aprosodias in patients with right hemispheric strokes. Secondary alexithymia, on the other hand, seems to be due to psychodynamic factors such as massive utilisation of defense mechanisms like denial, repression and regression. Appropriate psychotherapy for such patients is debatable, but it seems that in most cases the analytical approach should be replaced by more directive therapies, including relaxation and bio-feedback, to help patients learn to stimulate, master, and verbalize their emotions. The Beth Israel Questionnaire (BIQ) is a rating scale evaluating such traits that is filled out by the rater based on a clinical interview.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639000 TI - [X-ray computed tomographic abnormalities in schizophrenia. Trial of relationship with clinical data]. AB - Computerized tomography (CT-scan) studies in schizophrenia revealed that some patients have neuromorphological abnormalities. The structural changes consist mainly in lateral and third ventricle enlargement, and in cortical atrophy. The present study evaluates these three changes in 42 schizophrenics aged 18 to 50, compared to 24 healthy controls. Diagnosis were established from information gathered by personal interview with the SADS-LA. Clinical sub-types were evaluated according to the DSM III-R criteria. Moreover, detailed symptoms were rated according to the Positive And Negative Syndrome Scale (PANSS). CT scans were recorded in floppy disks and blindly analyzed. Schizophrenics shown significant higher mean size of lateral and third ventricles, and higher mean anterior cortical atrophy than healthy subjects. Significant differences were also found between subtypes, with more marked abnormalities in the disorganized group. The relationship between brain abnormalities and clinical symptoms recorded with the PANSS, were analysed using Pearson correlates. Positive correlations concerned mainly negative symptoms like blunted affect, emotional withdrawal, difficulties in abstract thinking, passive apathetic social withdrawal and lack of spontaneity of conversation. Positive correlations are also observed with some symptoms classified with the PANSS in the General Psychopathology scale such as mannerism and disorientation. Negative correlation concerned most of PANSS positive symptoms. PMID- 1639001 TI - [Panic disorder and microcirculation. Controlled study of capillaries in anxiety disorders]. AB - However varied the clinical descriptions of anxiety, a sizeable proportion is always allotted to the cardiovascular aspect. One is reminded of Krishaber's cerebral-cardiac neuropathy and Brissaud's conception of anxiety. The implication of the heart in anxiety disorders, especially paroxystic disorder, i.e. panic attacks (PA) is important. Cardiovascular symptoms (tachycardia, increased systolic blood pressure, chest pain) are among the most frequent manifestations of panic; furthermore, recent studies suggest that male panic disorder (PD) patients have an increased mortality risk from cardiovascular diseases. It is with this implication in mind that we undertook this study, the main aim of which was to confirm the existence of an abnormal microcirculation, characteristic of PD, taking the form of an excess number of twisted capillaries. Abnormal capillaries had been described previously in non-controlled studies of patients with psychiatric disorders diagnosed as neurasthenia, neurosis, neurovegetative disorders and more recently as neurocirculatory asthenia, a syndrome similar to PD. This led us to undertake a study of the total number of capillaries observed by photomicrography (capillaroscopy) in the supra-ungueal fold of the fingers of both hands (except thumbs), comparing the number of twisted capillaries of 16 subjects suffering from panic disorder with or without agoraphobia according to the DSM III-R criteria, with those of 16 healthy volunteers matched for age and sex and 14 subjects suffering from other anxiety disorders (10 of them fulfilling criteria for generalized anxiety disorders).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639002 TI - [Relations between mood disorders and personality. Recent data]. AB - In the field of studies of links between mood disorders and personality, the need to study only completely remitted patients has been demonstrated recently. Indeed, the clinically depressed state strongly influences the assessment of some personality traits in a more pathological direction (for instance for emotional stability, extraversion, interpersonal dependency, ego strength). The studies concerning unipolar depression have been mainly made according to two methodological approaches which results are relatively consistent. The first one uses batteries of standard self-report personality inventories such as the Hirschfeld and Klerman battery which includes the Guilford-Zimmerman Temperament Survey, the Interpersonal Dependency Inventory, the shortened version of the Lazare-Klerman-Armor Personality Inventory and two subscales of the MMPI. This approach shows that compared to normal population, recovered depressive, have less emotional strength more interpersonal dependency and a more introverted personality. The second approach uses diagnostic criteria of personality disorders according to DSM III. The clinical evaluation can be performed with the help of the Structured Interview for DSM III Personality Disorders (SIDP) or with of the help the Millon Clinical Multiaxial Inventory (MCMI), a self rated questionnaire. The most frequent personality disorder among recovered unipolar patients is dependent personality, followed by the avoidant and histrionic personalities and lastly the schizoid, schizotypal, borderline, compulsive and passive-aggressive personalities. But the interpretation of all these results must be cautious given that a recent study dealing with premorbid personality invites one to consider that not only depression influences personality assessment during illness, but also that depression may result in personality change after recovery. Few studies are available concerning bipolar patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639003 TI - [Lithium and aggression in adults]. AB - The use of lithium as an antiaggressive agent independently of its action in bipolar illness is now well documented. It appears particularly effective in the control of aggressive behavior in chronically aggressive prisoners and mentally retarded patients. Approximately 70-75% of these patients are likely to show a positive response to lithium therapy. No convincing features have been identified as being predictive of a good response. The clinical effect of lithium is to reduce the frequency and the severity of both hetero and auto aggressive outbursts. The use of lithium for aggressive behavior remains controversial in epileptic disorders and inconclusive in chronically psychotic patients. Careful monitoring of lithium blood levels is necessary to ensure adequate therapeutic efficacy without toxicity. A caution is needed in patients with brain damage especially when concurrent neuroleptic treatment is used. The antiaggressive effect of lithium seems rather specific and may be associated with a serotoninergic effect. PMID- 1639004 TI - [Effects of callosotomy in the treatment of intractable epilepsies in children on psychiatric disorders]. AB - Two children, 13 and 14 years old, presented an intractable epilepsy of Lennox Gastaut. In front of dangerous tonic and atonic epileptic crisis, a corpus callosotomy was performed. Corpus callosotomy is becoming a more widely used procedure in the treatment of intractable epilepsy as Lennox-Gastaut syndrome, or frontal epilepsy. However, there have been very few series that have reported results in children. It is not a complete but a partial, callosal section including approximately the anterior two thirds of the callosum. After this surgery the two children improved dramatically because the dangerous tonic and atonic crisis disappeared. Secondly we observed improvement of pre-surgical psychiatric troubles, that is a data not developed in the literature. Before surgery, the two children had a frontal syndrome with hyperkinesia, distractibility, aggressiveness, alexithymia, loss of the program of ideas. During the two months after the section of the anterior two thirds of the corpus callosum, we observed a progressive improvement of the frontal syndrome, with possibility to learn new praxies. The intellectual quotient was not altered and associative functions, depending of the posterior third of the corpus callosum were spared. Anti-epileptic medications were not stopped. We think that the improvement of the frontal syndrome is due to reduction of seizures. Therefore, we insist on the interest of the section of the anterior two thirds of the corpus callosum as treatment of tonic and atonic seizures but also as treatment of psychiatric symptoms depending of a frontal syndrome. PMID- 1639005 TI - The concept of negative feedback--Moore and Price. PMID- 1639006 TI - Thyroxine transport and the free hormone hypothesis. PMID- 1639007 TI - Developmental hormonal profiles accompanying the neonatal hypothyroidism-induced increase in adult testicular size and sperm production in the rat. AB - Neonatal treatment with the reversible goitrogen 6-N-propyl-2-thiouracil (PTU) results in a near doubling of testicular size and a 25% increase in the efficiency of spermatogenesis, without affecting circulating testosterone (T) levels in adult rats. The objectives of the present study were to examine the effects of neonatal PTU treatment on the pattern of testicular growth and circulating levels of anterior pituitary (FSH, LH, PRL, GH, and TSH), gonadal [immunoreactive inhibin-alpha (irI alpha) and T], and thyroid (T3 and T4) hormones over the first 100 days of life. Treatment of rats with PTU from birth to 24 days of age significantly reduced testicular weights between 10 and 60 days of age. However, the duration of testicular growth was extended in treated males, resulting in a 68% increase at 100 days of age. Serum gonadotropin levels in treated males were reduced throughout the experimental period, typically remaining between 50-70% of control levels. The characteristic robust prepubertal FSH peak was absent in PTU-treated males. Initially high until 20 days of age, irI alpha levels characteristically declined to adult levels (200-300 pg/ml) in control males. In treated males, irI alpha levels were reduced during the period of hypothyroidism, increased between 30 and 60 days, and then declined, but remained significantly higher (1.7- to 2-fold greater) than those observed in control males. Serum T levels were similar in treated and control males. Control males demonstrated increased T levels beginning at 45 days of age, earlier than observed in treated males; however, similar peak T levels were observed in all males. PTU treatment significantly suppressed serum GH and PRL and led to a 14 fold increase in circulating TSH during the period of treatment. However, unlike the gonadotropins, these hormones returned to control levels after PTU treatment, suggesting that the reduced levels of FSH and LH observed are not due to a generalized reduction in pituitary function. Serum T4 and T3 levels returned to control levels within 15 days after the removal of PTU. These results demonstrate that the neonatal PTU treatment-induced increases in adult testicular size and sperm production were not due to increased levels of FSH at any point in development. On the contrary, the observed increases occur in spite of chronically reduced FSH levels. PMID- 1639008 TI - Thyroid albumin originates from blood. AB - Iodoalbumin has been found in the goiter of Dutch goats with a thyroglobulin synthesis defect. Immunohistochemical studies showed that in the goiter the percentage of follicles containing albumin was higher than that in normal thyroid glands. In the albumin-containing follicles of normal and goitrous glands, transferrin and immunoglobulin G could be found. Also, between the epithelial cells, serum proteins were detected. These results indicate intercellular passage of serum proteins. After in vivo labeling with 125I, goiter slices were incubated with [3H] leucine. Purified 125I-containing albumin did not contain [3H]leucine, while thyroglobulin antigens were double labeled. Cyanogen bromide treatment of albumin out of the goiter and of serum albumin gave comparable cleavage patterns, indicating that no great differences in amino acid composition, especially methionine, exist. In total RNA from goiter, no albumin mRNA could be detected after blotting and hybridization with goat albumin cDNA. Also, the polymerase chain reaction method with albumin DNA primers was unable to detect any albumin mRNA in normal and goitrous glands of goats. From these results we conclude that "thyralbumin" originates from blood and is not synthesized by the thyroid gland. PMID- 1639009 TI - Prolactin isoform 2 as an autocrine growth factor for GH3 cells. AB - Because PRL has growth factor activities in several tissues, we have asked whether it also has autocrine growth factor activity in pituitary GH3 cells. GH3 cells were grown at increasing densities in the presence or absence of antirat PRL (polyclonal and monoclonal) or nonspecific antibodies. Cell proliferation increased with increasing cell density, as did the concentration of PRL in the medium. Antirat PRL, but not control antibody, markedly inhibited but did not eliminate cell proliferation, and this effect was diminished with increasing PRL concentration in the medium. PRL receptors were demonstrated on 40-50% of the cells by indirect immunofluorescence using a specific antirat PRL receptor monoclonal antibody. Cell surface PRL was colocalized to the same 40-50% of the cells and copatched or cocapped along with the receptors. Absence or presence of PRL receptors did not correlate with stage of the cell cycle, as judged by ethidium bromide dual labeling. Cell surface PRL was found to be on PRL containing cells. These data have fulfilled four criteria necessary for establishment of a substance as a secreted autocrine growth factor: 1) the factor must be secreted; 2) in log growth phase, increased cell proliferation should occur at increased cell densities; 3) the cells must display a receptor for the factor; and 4) there must be a growth response to the factor. Thus we have established that PRL is an autocrine growth factor for at least 40-50% of the GH3 cell population. This, to our knowledge, is the first example of autocrine growth factor activity of a major hormone normotopically expressed. PMID- 1639010 TI - Endothelin-1 actions on resorption, collagen and noncollagen protein synthesis, and phosphatidylinositol turnover in bone organ cultures. AB - The effects of endothelin-1 (ET) on several tissues are mediated by prostaglandins. In this study, we investigated the actions of ET on bone and determined whether they are mediated through prostaglandin-dependent pathways. Bone resorption, collagen, and non-collagen protein synthesis and inositol phosphate (IP) production were studied in neonatal mouse calvaria and fetal rat limb bone cultures. The effects of ET in the calvaria model were examined in the presence or absence of the cyclooxygenase inhibitor indomethacin (INDO). Bone resorption was stimulated by ET in the neonatal mouse calvaria, and this effect was inhibited by INDO. 45Ca release in the fetal rat limb bones was not affected by ET. ET stimulated collagen and noncollagen protein synthesis significantly in the calvaria model in the presence but not in the absence of INDO, suggesting that the anabolic effects of ET were masked by endogenous prostaglandin production. ET increased phosphatidylinositol turnover in both bone organ cultures. Although the addition of INDO reduced IP production slightly in the mouse calvaria, it was still significantly stimulated by ET. Our results demonstrate that ET has marked effects on bone tissue in vitro. Effects on resorption appear to be prostaglandin dependent, whereas the anabolic effects were not prostaglandin mediated. The stimulatory effects of ET on protein synthesis could be mediated through the IP signaling pathway. Since ET stimulates both bone resorption and anabolism, this peptide may have a role in the coupling of bone remodeling. PMID- 1639011 TI - In vitro study of acute toxic effects of high iodide doses in human thyroid follicles. AB - The acute effects of increasing doses of sodium iodide were studied on human thyroid follicles isolated from normal paranodular tissue. After 24 h incubation in culture medium, follicles isolated from most thyroids maintained their capacity for 125I accumulation and organification and a normal cellular ultrastructure. 125I accumulation was significantly increased after addition of TSH, whereas 125I organification was not affected. In presence of TSH, numerous follicles had large empty-looking follicular lumina unlabeled on autoradiographies. Follicles incubated for 24 h in the presence of a low concentration (10(-7) M) of iodide retained their function and morphology. However, incubation with a high dose of iodide (10(-3) M) caused marked inhibition of 125I accumulation and organification reaching values similar to those obtained in presence of inhibitors of iodide trapping and organification. At high doses, iodide induced necrosis of thyroid epithelial cells: the percentage of necrotic cells was significantly increased with 10(-5) M and doubled with 10(-3) M as compared to values measured at 10(-7) M. Ultrastructural lesions such as apical blebbing, cytoplasmic fragments desquamation, endoplasmic reticulum vesiculation, and accumulation of lipofuscin in secondary lysosomes were also present. The necrotic effect and the ultrastructural alterations also occurred in the presence of TSH but were prevented by the addition of inhibitors of iodide trapping or organification. These results demonstrate a direct acute toxic effect of iodide in human thyroid cells. The nature of the ultrastructural alterations is in agreement with a mechanism of toxicity involving a free radical attack and lipid peroxidation as observed in other tissues. PMID- 1639012 TI - Synergistic effect of insulin-like growth factor-I administration on the protein sparing effects of total parenteral nutrition in fasted lambs. AB - Using primed constant isotopic infusions, we investigated the effects of recombinant human insulin-like growth factor-I (IGF-I) infusion on protein kinetics in both fasted and parenterally fed (TPN) lambs. Infusion of IGF-I at a dose of 50 micrograms/kg.h in fasted animals increased (P less than 0.005) the mean plasma IGF-I concentration from 77.5 +/- 9.7 to 454.4 +/- 51.4 ng/ml. During IGF-I infusion the rate of net protein catabolism (NPC) was decreased (P less than 0.005) by 17% from 3.5 +/- 0.2 to 2.9 +/- 0.2 g/kg.day, and the rate of appearance (Ra) of leucine in plasma decreased (P less than 0.01) from 5.0 +/- 0.4 to 3.4 +/- 0.4 mumol/kg.min. In addition, the fractional synthetic rate of protein in cardiac and diaphragmatic muscle increased by 100% (P less than 0.05) during the same period. After 3 h of TPN, the rate of NPC was decreased (P less than 0.01) in the TPN animals compared to that in their fasted counterparts (1.89 +/- 2.27 vs. 4.1 +/- 0.2 g/kg.day, respectively). The rate of NPC was further decreased after another 300 min of TPN to 0.76 +/- 0.27 g/kg.day. However, the Ra of leucine was not changed compared to the initial value. Infusion of IGF-I concurrently with TPN reversed (P less than 0.001) the rate of NPC from 1.02 +/- 0.21 g/kg.day after 180 min of TPN alone to a state of net protein gain of 0.14 +/- 0.19 g/kg.day after a further 300 min of combined IGF-I and TPN infusion. The Ra of leucine decreased (P less than 0.01) from 3.9 +/- 0.8 to 2.5 +/- 0.47 mumol/kg.min during IGF-I and TPN infusion. Similarly, the fractional synthetic rates of protein in cardiac muscle, diaphragm, adductor muscle, psoas muscle, and hepatic tissue were increased (P less than 0.05) compared to those in animals that received only TPN. The protein-sparing effects of IGF-I and TPN were synergistic, and the infusion of both agents resulted in the induction of a protein anabolic state within 60 min of commencing IGF-I infusion. In contrast, neither IGF-I nor TPN alone resulted in a state of net protein anabolism, and neither had an effect on protein kinetics until 120 min into the infusion. Consequently, IGF-I shows considerable potential as an anticatabolic agent when used synergistically with nutritional support. PMID- 1639013 TI - Insulin regulation of messenger ribonucleic acid for the surfactant-associated proteins in human fetal lung in vitro. AB - Respiratory distress syndrome (RDS) is primarily caused by an immaturity in the synthesis and secretion of surfactant by the fetal lung type II cell. Fetal hyperinsulinemia associated with maternal diabetes places the newborn at an increased risk of developing RDS, and therefore, it has been hypothesized that insulin inhibits type II cell differentiation. We have previously shown that insulin inhibits the accumulation of surfactant-associated protein A (SP-A), the major surfactant-associated protein, in human fetal lung explants maintained in vitro. In the present study, we used Northern blot analysis to evaluate the effects of insulin on the content of SP-A messenger RNA (mRNA) as well as on the content of mRNA for the hydrophobic surfactant-associated proteins SP-B and SP-C in human fetal lung explants maintained in vitro. Lung explants were maintained in serum-free medium with or without added insulin (0.25-2500 ng/ml) for up to 6 days. We observed that insulin, at concentrations of 25-2500 ng/ml, significantly inhibited the accumulation of SP-A mRNA when compared to controls (P less than 0.01). The inhibitory effect of insulin on SP-A mRNA accumulation was dose dependent with an approximately 75% inhibition observed at 2500 ng/ml. Insulin, at the concentration of 2500 ng/ml, significantly inhibited the accumulation of SP-B mRNA by approximately 30% when compared to control levels (P less than 0.01) but had no effect at lower concentrations. Insulin had no significant effect on SP-C mRNA levels at any concentration tested. Our findings provide evidence that insulin may delay fetal lung development by inhibiting SP-A and SP-B gene expression. A deficiency of these proteins in pulmonary surfactant may account for the increased incidence of RDS in infants of diabetic mothers. PMID- 1639014 TI - Interleukin-2 induces corticotropin-releasing hormone release from superfused rat hypothalami: influence of glucocorticoids. AB - The present work shows that interleukin-2 (IL-2) is able to increase in a dose dependent manner (25-100 U/ml) CRF release from continuous perifused hypothalami. The effects of IL-2 and IL-1 on CRF secretion are potentiated by the simultaneous action of the two cytokines at the hypothalamus. The stimulatory effect of IL-2 on CRF secretion is significantly inhibited by the presence of dexamethasone in the perifusion medium. However, the CRF response to IL-2 was similar in adrenalectomized animals and sham-operated rats. It is suggested that the action of IL-2 on hypothalamic CRF secretion is integrated in the communication between the immune system and the hypothalamic-pituitary-adrenocortical axis, and that such action is subjected to glucocorticoid negative feedback modulation. The mechanism underlying the effect of IL-2 on CRF release is unknown, but arachidonic acid metabolites do not seem to be involved, since neither a lipooxygenase (nordihidrogueretic acid) nor a cyclooxigenase (indomethacin) inhibitor affected the hypothalamic secretory response to IL-2. PMID- 1639015 TI - Neuropeptide Y release is elevated from the microdissected paraventricular nucleus of food-deprived rats: an in vitro study. AB - Intracerebroventricular injection of neuropeptide Y (NPY) stimulates a robust dose-related feeding response in the rat. Experimental evidence attests to the view that the release of NPY in the paraventricular nucleus (PVN), a site richly innervated by NPY immunopositive fibers, is responsible for stimulation of feeding behavior. However, there is little information on the neuroendocrine factors involved in regulation of NPY release, in part due to the unavailability of reliable techniques to monitor PVN NPY release. In this study, we have validated an in vitro technique to assess NPY release from the PVN and other neighboring hypothalamic sites of the rat brain. In the first experiment, freshly dissected brains from male rats were processed for 300-microns thick sections with a vibratome. The PVNs were microdissected from the brain sections under a stereomicroscope and incubated in 250 microliters Krebs Ringer bicarbonate buffer at 37 C for basal and KCl-induced NPY release. The results showed that basal NPY efflux from the excised PVN was detectable and increased in relation to the number of PVNs in the incubation chambers. Addition of KCl at the end of the 60 min basal incubation period increased NPY release further, the increments were again closely related to the number of PVN punches in the incubation chambers. In the second experiment, the assumption that in vitro basal and KCl-evoked NPY release from the PVN reflected the in vivo pattern of PVN NPY secretion was validated. The effects of 4-day food deprivation (FD), an experimental paradigm known to augment in vivo PVN NPY secretion, on the in vitro NPY release from PVN and ventromedial nucleus were evaluated. The results showed that both basal and KCl-evoked NPY release was significantly higher from the PVN of food-deprived than control rats on ad libitum rat chow. This FD-induced incremental NPY response was site-specific because the basal and KCl-evoked NPY effluxes from the ventromedial nucleus of FD and control rats were similar. Thus, in agreement with previous in vivo findings, NPY release in vitro is also augmented selectively from the PVN in response to fasting. Cumulatively, these results demonstrate that NPY release in vitro from hypothalamic sites microdissected from fresh brains can be assessed in a reliable fashion and are in accord with the proposal that enhanced NPY action within the PVN is responsible for increased drive for food. PMID- 1639016 TI - The regulation of porcine theca cell proliferation in vitro: synergistic actions of epidermal growth factor and platelet-derived growth factor. AB - An important but poorly understood aspect of mammalian follicle development involves the regulation of theca cell proliferation. To investigate the premise that growth factors regulate theca cell proliferation, porcine theca cells were prepared by collagenase/DN'ase digestion of follicle linings after the removal of the granulosa cells and allowed to attach for 24 h. This method provided a monolayer of theca cells that had little if any granulosa cell contamination and which secreted high levels of androstenedione relative to granulosa cells during moderate-term culture (33-fold difference, P less than 0.01). In medium containing fetal calf serum (10%), theca cells were significantly more responsive to platelet-derived growth factor (PDGF) than epidermal growth factor (EGF) in terms of proliferation (13.4 +/- 0.2-vs. 7.0 +/- 0.1-fold increases relative to the initial cell count, P less than 0.05). This is in contrast to granulosa cells which were significantly more responsive to EGF than PDGF (7.1 +/- 0.1 vs. 4.0 +/ 0.2 fold-increases, P less than 0.05). Since serum has been shown to contain both EGF and PDGF, proliferation studies were performed using plasma-derived serum (PDS) which is growth factor restricted to examine more closely the direct effects of growth factors. In medium containing 0.25% PDS and within experiments, PDGF (1-25 ng/ml) stimulated theca cell proliferation in a dose-dependent manner (2.3-fold increase relative to controls, P less than 0.05) whereas EGF did not. EGF, however, markedly enhanced the proliferative action of PDGF (6.4-fold increase relative to controls, P less than 0.05). Insulin-like growth factor I and low density lipoprotein, factors which enhance markedly the proliferative effects of EGF and PDGF in terms of granulosa cell proliferation, exhibited only a modest synergistic effect with respect to EGF and PDGF upon theca cells (9.5 fold increase vs. a 6.4-fold increase above controls, P less than 0.05). Temporal studies in vitro indicate that theca cell proliferation is low during the first 3 day exposure to growth factors irrespective of treatment (a 2-fold increase over the seeding density). During the second 3-day exposure, however, theca cell proliferation increases 4- to 5-fold. The temporal pattern of theca cell proliferation stimulated by fetal calf serum supplemented with EGF or PDGF and PDS-containing medium supplemented with PDGF, EGF, insulin-like growth factor I, and low density lipoprotein is similar. These results suggest that PDGF is a major mitogen toward porcine theca cells and that EGF greatly enhances its activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1639017 TI - Prolactin enhancement of its own uptake at the choroid plexus. AB - The choroid plexus contains PRL receptors that function in part to transport PRL from the blood into the cerebrospinal fluid (CSF). The blood PRL concentration of female rats was altered by 1) three daily injections of haloperidol (chronic hyperprolactinemia) with or without bromocriptine administration 4 h before death, 2) bromocriptine alone for 4 h (acute hypoprolactinemia), and 3) a single vascular injection of ovine PRL (acute hyperprolactinemia). Changes in the uptake of PRL by the choroid plexus was assessed by quantitative in vivo autoradiography after the injection of radiolabeled PRL. Correlation of changes in PRL uptake at the choroid plexus with changes in PRL transport from blood to CSF was evaluated by subjecting CSF samples to sodium dodecyl sulfate-polyacrylamide gel electrophoresis after vascular injection of radiolabeled PRL. Autoradiography revealed that both chronic and acute hyperprolactinemia resulted in a significant increase in the uptake of radiolabeled PRL by the choroid plexus compared to that in untreated control animals. In contrast, bromocriptine had no effect on PRL uptake at the choroid plexus relative to that in control (untreated) animals. Chronic hyperprolactinemia, but not acute hyperprolactinemia, resulted in a significant increase in the transport of radiolabeled PRL from the blood to the CSF compared to that in untreated controls. The results are consistent with the up-regulation of PRL receptors in the choroid plexus by circulating PRL and the consequent augmentation of transport of PRL from blood to CSF. PMID- 1639018 TI - IL-6 increases endothelial permeability in vitro. AB - The effect of interleukin 6 (IL-6) on endothelial permeability was examined by measuring fluorescein isothiocyanate-labeled albumin flux across an endothelial cell monolayer. Bovine vascular endothelial cells (BVEC) were cultured up to confluency on collagen-coated polycarbonate micropore filters and then the filters were mounted on modified Boyden chambers. Treatment of the BVEC with IL-6 at 100 ng/ml for 21 h caused a remarkable increase in the permeability of fluorescein isothiocyanate-labeled albumin across the endothelial monolayer. This effect of IL-6 was concentration dependent, in the range from 10-200 ng/ml of IL 6. The effect of IL-6 was also time dependent, the maximal level being reached at 21 h from the beginning of the treatment. This stimulatory effect of IL-6 on albumin clearance was completely abolished by the addition of anti-IL-6 antibody. Light microscopic observation of a cross-section of a monolayer showed that the IL-6-induced increase in the permeability was correlated with changes in cell shape and rearrangement of intracellular actin fibers. IL-6 did not show any cytotoxicity toward or growth inhibition of endothelial cells, even at more than 200 ng/ml. The enhancing effect of IL-6 on the increase in the permeability was reversible; when IL-6 was removed by a medium change and the cells were incubated for a further 24 h without IL-6, the permeability was restored to the control level. These results suggest that IL-6 can induce an increase in endothelial permeability in vitro by rearranging actin filaments and by changing the shape of endothelial cells. PMID- 1639019 TI - Activity of vasoactive intestinal peptide and serotonin in the paraventricular nucleus reflects the periodicity of the endogenous stimulatory rhythm regulating prolactin secretion. AB - PRL secretion in the female rat is regulated by an endogenous stimulatory rhythm (ESR) of prolactin-releasing factors of hypothalamic origin which has a bimodal periodicity with distinct nocturnal (N) and diurnal (D) phases. The N phase reaches peak magnitude by 0300 h and the D phase reaches peak magnitude by 1700 h. This rhythm was first unmasked in ovariectomized rats by correctly timed injection of a dopamine antagonist. OT, vasoactive intestinal peptide (VIP), and serotonin (5-HT) are differentially involved in generating the ESR. Pharmacological studies suggest that OT is the neurohormone and VIP and 5-HT are neuromodulators which act to stimulate OT release. Recently, we reported that activity of OTergic neurons in the paraventricular nucleus (PVN) and OT concentrations in the anterior pituitary mirror the periodicity of the ESR. The present experiments were conducted to determine if VIP and 5-HT activity in the hypothalamus also mirrors the periodicity of the ESR. Push-pull cannulae were surgically implanted in the PVN of ovariectomized female rats. Following recovery, push-pull perfusion was conducted from either 0600-1400 h, 1400-2200 h, or 2200-0600 h. VIP was measured in perfusates by RIA. There was no difference in VIP pulse frequency between rats perfused during the three periods studied. However, animals perfused from 2200-0600 h had significantly greater pulse amplitude as compared to rats at either 0600-1400 h or 1400-2200 h. Activity of 5 HTergic neurons in the hypothalamus was studied by estimating the turnover of 5 HT 10 min following the injection of pargyline. Hypothalamic nuclei were dissected using Palkovits' punch technique and 5-HT concentration assayed by HPLC in conjunction with electrochemical detection. Turnover of 5-HT was estimated by calculating the slope of the accumulation of 5-HT over 10 min at differing times of day using least squares regression analysis. There was a distinct diurnal rhythm of 5-HT accumulation in the PVN. Rats killed at 1700 h had significantly greater slopes of 5-HT accumulation in the PVN than rats killed at either 0300 or 1200 h. Similarly, there was a diurnal rhythm of 5-HT turnover in the suprachiasmatic nucleus. Rats sampled at either 1200 or 1700 h had significantly greater slopes of 5-HT accumulation in the suprachiasmatic nucleus than rats sampled at 0300 h. There was no diurnal rhythm of 5-HT turnover evident in either the median eminence or the supraoptic nucleus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1639020 TI - Activation of the phosphatidylinositol pathway in the primate corpus luteum by prostaglandin F2 alpha. AB - The current study was designed to investigate the ability of prostaglandin F2 alpha (PGF2 alpha) to activate a second messenger system (phosphatidylinositol pathway) in corpora lutea (CL) of rhesus monkeys. Activation of this pathway was assessed by monitoring the hydrolysis of phosphatidylinositol to inositol phosphates. Since inositol triphosphate mobilizes intracellular Ca2+, intracellular free calcium concentrations ([Ca2+]i) were also assessed in individual cells by fura-2 fluorescence photometry. These responses to PGF2 alpha were measured in luteal cells collected from nonpregnant rhesus monkeys. CL were collected during the early (days 4-5 after estimated LH surge; n = 4), mid (days 8-9; n = 4), and late (days 13-14; n = 5) luteal phase and 1 day after in vivo hCG treatment (15 IU/dose, morning and evening), which began during the midluteal phase (n = 5). PGF2 alpha significantly increased the accumulation of inositol phosphates in all groups (P less than 0.05), except the midluteal phase (P = 0.07). The luteal sensitivity to PGF2 alpha, judged by phosphatidylinositol hydrolysis, was low in the early to midluteal phase compared to that in the late luteal phase and after in vivo hCG treatment. PGF2 alpha also caused a rapid, yet transient, increase in [Ca2+]i in a large proportion of primate luteal cells. The proportion of luteal cells that responded to PGF2 alpha with an increase in [Ca2+]i was smaller (P less than 0.05) in CL collected during the early luteal phase than in the other groups. Luteal progesterone production was inhibited by PGF2 alpha in CL collected after in vivo hCG. CL treated in vivo with hCG also displayed in vitro the largest increases in phosphatidylinositol hydrolysis and [Ca2+]i in response to PGF2 alpha. Therefore, this study demonstrates that PGF2 alpha is a potent activator of the phosphatidylinositol pathway in the primate CL. This activation is augmented as the luteal phase progresses and is influenced by in vivo hCG treatment. This study also provides evidence that the inhibitory effects of PGF2 alpha on progesterone production are associated with the activation of the phosphatidylinositol pathway. PMID- 1639021 TI - Synergistic interaction between insulin-like growth factors-I and -II in central regulation of pulsatile growth hormone secretion. AB - Insulin-like growth factor (IGF)-I and -II peptides, receptors, mRNAs, and binding proteins are widely distributed in the central nervous system (CNS), yet their physiological role in the brain remains largely unknown. While earlier in vivo studies in the rat suggested that IGF-I may participate in feedback regulation of GH secretion at a CNS level, the preparations used were only partially pure. The recent availability of purified recombinant IGF-I and -II peptides prompted us to reexamine the involvement of the IGFs in vivo in central regulation of pulsatile GH secretion. Five groups of free-moving adult male rats bearing chronic intracerebroventricular (icv) and intracardiac venous cannulae were icv administered IGF-I (in doses of 0.5, 2, 3, and 10 micrograms) or the acid-saline vehicle; an additional group received 1 microgram of the potent IGF-I analog, long R3 IGF-I. Spontaneous 6-h plasma GH secretory profiles were obtained from all groups. Vehicle-injected control animals exhibited the typical pulsatile pattern of GH secretion, with most peak GH values above 150 ng/ml and trough levels below 1.2 ng/ml. Central administration of IGF-I alone or long R3 IGF-I at all doses tested failed to alter the pulsatile pattern of GH release; there were no significant differences in GH peak amplitude, GH trough level, GH interpeak interval, or mean 6-h plasma GH level compared to those in vehicle-injected controls. In a second study, designed to determine the effects of central administration of IGF-I and IGF-II, in combination, icv injection of 1 microgram IGF-I and 1 microgram IGF-II resulted in a marked suppression in the amplitude of spontaneous GH secretory bursts approximately 3 h after injection; both GH pulse amplitude (43.5 +/- 5.6 vs. 130.6 +/- 14.6 ng/ml; P less than 0.001) and mean plasma GH level (16.3 +/- 1.9 vs. 35.2 +/- 1.8 ng/ml; P less than 0.001) were severely reduced 3-6 h after injection compared to those in vehicle-injected controls. These results demonstrate that IGF-I alone does not play a physiologically important role in feedback regulation of GH secretion at the level of the CNS. Our findings suggest a synergistic interaction between IGF-I and -II in the brain for central control of pulsatile GH secretion. PMID- 1639022 TI - Antithyrotropin-releasing hormone serum inhibits secretion of glucagon from isolated perfused rat pancreas: an experimental model for positive feedback regulation of glucagon secretion. AB - TRH is synthesized in the islets of Langerhans and was found in the perfusate of isolated rat pancreas. In the present study, designed to determine the role of endogenous TRH, we first characterized chromatographically the identity of immunoreactive TRH with synthetic pGlu-His-Pro-NH2. Since endogenous TRH secretion may mask the effects of exogenous TRH, we performed, in parallel to dose-response studies, immunoneutralization experiments using anti-TRH serum to neutralize the endogenous TRH secretion from isolated perfused rat pancreas. The data indicate that exogenous TRH enhances basal glucagon secretion; inversely, anti-TRH serum inhibits glucose plus arginine-induced glucagon secretion and produces a concomitant slight inhibition of somatostatin secretion. The present study shows a physiological contribution for endogenous TRH as a local modulator of intraislet hormone regulation; from these observations, we postulate a direct effect of pancreatic TRH on glucagon-containing (alpha) cell secretion, which, in turn, may produce the fluctuation in somatostatin secretion. Local TRH secretion provides a model for positive feedback regulation of glucagon secretion, frequently associated with diabetes. PMID- 1639023 TI - Growth hormone increases intracellular free calcium in rat adipocytes: correlation with actions on carbohydrate metabolism. AB - Adipocytes that have been preincubated for 3 h or more in hormone-free medium respond to GH with a transient insulin-like increase in glucose metabolism, followed by a period of refractoriness to further insulin-like stimulation. Adipocytes freshly isolated from normal rats and adipocytes that were exposed to GH in the first hour of a 4-h incubation period are refractory to this insulin like effect. Because earlier studies revealed a relationship between refractoriness and cellular calcium, we examined the effects of GH on the intracellular calcium concentration ([Ca2+]i) under a variety of conditions in which sensitivity to insulin-like stimulation or refractoriness is known to be affected. A dual nitrogen laser imaging microscope with computer-assisted image processing to measure fluorescence changes in individual adipocytes loaded with fura-2 AM was used to measure [Ca2+]i. After prolonged incubation in vitro, resting [Ca+2]i was 120 +/- 6 nM and remained unchanged for more than 1 h after the addition of 100 ng/ml human GH (hGH), which doubled the rate of incorporation of [3-3H] glucose into triglycerides in this interval. Lipogenesis declined in the second hour, and [Ca+2]i slowly increased, reaching 324 +/- 49 nM by the end of the third hour (P less than 0.05). When added with GH, actinomycin-D, an inhibitor of RNA synthesis, caused the accelerated rate of lipogenesis to persist for at least 5 h and blocked the delayed increase in resting [Ca+2]i. Resting [Ca2+]i in freshly isolated, and hence refractory, adipocytes was 342 +/- 34 nM and declined to 112 +/- 11 nM concomitant with acquisition of insulin-like sensitivity to GH. The addition of 100 ng/ml hGH to these cells at the beginning of incubation, under conditions known to sustain refractoriness prevented the decline in resting [Ca2+]i and enabled them to exhibit a further acute increase in [Ca2+]i in response to a second exposure to hGH in the fourth hour. When added 60 min after GH, actinomycin-D blocked the ability to raise [Ca2+]i acutely in response to GH, but did not interfere with GH's action to sustain resting [Ca2+]i, which remained at about 300 nM. The concentration of GH needed to increase [Ca2+]i acutely in refractory cells is about 6-fold higher than that needed to maintain resting [Ca+2]i. Differences in the time of sensitivity to actinomycin-D and dose dependency suggest that sustaining resting [Ca2+]i and production of the acute increase in [Ca2+]i are separate phenomena.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1639024 TI - Effect of hypothalamic lesions that induce precocious puberty on the morphological and functional maturation of the luteinizing hormone-releasing hormone neuronal system. AB - Recent evidence has implicated the transforming growth factor-alpha (TGF alpha)/epidermal growth factor receptor (EGFR) system in the mechanism by which hypothalamic lesions accelerate female sexual development. Since acquisition and maintenance of reproductive functions depend on the secretory activity of LHRH neurons, the present studies were undertaken to characterize some of the cellular and molecular events that underlie lesion-induced activation of the LHRH neuronal network. Bilateral electrolytic lesions of the posterior portion of the preoptic region and anterior hypothalamic area (POA-AHA) in 22-day-old rats resulted in vaginal opening and ovulation within 7 days. Morphological maturation of LHRH neurons was assessed by the relative frequency of irregular and smooth neurons (the former being the predominant type in adult animals). Within 20 h after the lesion, there was a significant decrease in the proportion of LHRH neurons with spiny irregular contours, indicating reversal to a more immature morphological type. This change was followed by accelerated spine reformation, so that at the time of precocious proestrus, the incidence of irregular LHRH neurons was similar in lesioned and age-matched control rats. A striking increase in c-fos mRNA levels occurred within 1 h after the lesion in the area neighboring the site of injury, reflecting the immediate cell response to trauma. Immunohistochemical localization of the c-fos protein, used to estimate changes in cellular activity at the single cell level, demonstrated c-fos induction in unidentified cells near the lesion and astrocytes, but not in LHRH neurons 20 h after injury. In contrast, a selective increase in c-fos expression was observed in LHRH neurons during the initiation of precocious puberty 5-7 days later at the time of the first proestrus. An increase in plasma LH associated with a drop in LHRH content in the median eminence and an increase in pro-LHRH precursor in the POA-AHA, with no changes in LHRH mRNA, was found to antedate the first preovulatory surge of gonadotropins in lesioned rats. Assessment of the changes in PC2 mRNA, which encodes a novel dibasic endoprotease presumptively involved in tissue-specific processing of a class of prohormones that includes pro-LHRH, showed that the content of PC2 mRNA in the AHA-POA increases during normal puberty, but not in lesioned animals, thus providing a potential explanation for the divergent changes in pro-LHRH and mature decapeptide found in lesioned rats.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1639025 TI - Specific antibody to the thyrotropin receptor identifies multiple receptor forms in membranes of cells transfected with wild-type receptor complementary deoxyribonucleic acid: characterization of their relevance to receptor synthesis, processing, structure, and function. AB - An antibody to a peptide of the TSH receptor, residues 352-366 which are not present in gonadotropin receptors, specifically identifies three major forms of the receptor on Western blots of detergent-solubilized membrane preparations from Cos-7 cells transfected with full-length rat and human TSH receptor cDNA: 230, 180, and 95-100 kilodaltons (kDa), based on simultaneously run protein standards. The 95- to 100-kDa protein is absent in cells transfected with a mutant receptor with no signal peptide and is sensitive to endoglycosidase-F. Its size is consistent with the sum of amino acids predicted from its cDNA sequence (84 kDa after subtracting the signal peptide) plus its carbohydrate content (14 kDa estimated from glycosylation mutants). It alone is absent in two deletion mutants that have lost TSH binding and activity after transfection: M1 missing residues 37-121 and M2 missing residues 110-307. It, thus, appears to be the processed glycosylated functional receptor on the cell surface. The 230-kDa protein is a nonprocessed form of the receptor, as evidenced by its insensitivity to endoglycosidase-F and its continued presence in cells transfected with a mutant receptor with no signal peptide. It is the primary form identified in rat FRTL-5 thyroid cells that have a functioning TSH receptor; it is not present in rat FRT thyroid cells with no functioning TSH receptor or receptor RNA. It appears, therefore, to be a early synthetic form of the functional TSH receptor. The 180 kDa protein is endoglycosidase-F sensitive and appears to be a processed intermediate between the 230-kDa early synthetic form and the 95- to 100-kDa functional receptor, rather than a dimer of the latter. Thus, with decreases in size appropriate to a receptor monomer, it remains present in membranes from the M1 and M2 deletion mutants that contain the 230-kDa protein but are missing the 95- to 100-kDa receptor form in association with lost TSH binding and activity after transfection. Minor receptor forms (54 kDa in rat receptor transfectants, 54 and 48 kDa in human receptor transfectants) appear to be degraded forms of the processed and glycosylated 95- to 100-kDa receptor. The presence or absence of reducing agents in the detergent solubilization mixture does not change the pattern or amount of the receptor forms recognized by the antibody, including the 54-kDa form; however, boiling does.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1639026 TI - A study of the characteristics of hepatic iodothyronine 5'-monodeiodinase in various vertebrate species. AB - Rat type I iodothyronine 5'-monodeiodinase (5'-MD) has recently been shown to be a selenium-containing enzyme. In the present study we compared the characteristics of the 5'-MD from liver microsomes of rat, mouse, guinea pig, man, beef, pig, sheep, and chicken. Aurothioglucose (ATG), a known potent inhibitor of selenium-containing enzymes, was a consistent, very potent inhibitor of 5'-MD activity in all species studied, with a 50% inhibitory dose in the narrow range of 5.8-12 nM. ATG was also a potent and selective inhibitor of [125I]bromoacetyl T3 affinity labeling of 5'-MD. Thus, in the species studied, only one affinity-labeled band, which was selectively displaced by gold, was identified. The mol wt of the affinity-labeled proteins in various liver microsomal preparations ranged between 28-36 kilodaltons (kDa), and the ATG concentrations necessary for the inhibition of affinity labeling of microsomes with [125I]bromoacetyl T3 were comparable to those required for inhibition of the enzyme activity in all species except the pig. The pig liver microsomes demonstrated a dominant affinity-labeled 36-kDa band, but much higher ATG concentrations (micromolar) were required for inhibition of affinity labeling. In view of the potent inhibition of pig liver 5'-MD activity by ATG, it appears unlikely that this band in the pig corresponds only to the substrate-binding site of 5'-MD, but this issue requires further study. A synthetic peptide of 16 amino acids corresponding to the carboxy-terminal portion of rat 5'-MD was synthesized, and rabbits were immunized with the peptide-BSA conjugate. Western blot studies using the rabbit antiserum showed one specific 29-kDa band in rat liver and kidney microsomes and thyroid homogenate. No specific bands were observed in other adult rat tissues studied or in fetal rat liver. No specific bands were observed when Western blot studies with antibody against the carboxy-terminal portion of rat 5'-MD were performed in liver microsomes from species other than the rat. In conclusion, our studies indicate that selenium is a likely component of type I 5'-MD in all species studied. However, substantial structural differences exist between the rat type I 5'-MD and that in various other species. PMID- 1639027 TI - Hypoglycemic action of a novel constrained analog of human growth hormone-(6-13). AB - The amino-terminal region of human GH (hGH), in particular the amino acid sequence Leu-Ser-Arg-Leu-Phe-Asp-Asn-Ala[hGH-(6-13)], has been implicated as a functional region for the regulation of energy metabolism by exerting an insulin potentiating action on insulin-sensitive tissues. Recent structural studies have revealed that the cyclization of the aspartate (Asp11) residue to form the alpha aminosuccinimide (Asu11) ring is essential for the biological action of peptides related to this hGH fragment. The pharmacological application of these hGH-(6-13) peptides has been hindered by the vulnerability of the alpha-aminosuccinimide to hydrolytic modification leading to the loss of biological action. We have succeeded in stabilizing the structure of the Asu11-hGH-(6-13) peptide by replacing the alpha-aminosuccinimide ring with compatible and less rapidly metabolized gamma-lactam structures. In the present paper we report the bioactivity profile of an analog of hGH-(6-13) containing a gamma-lactam at residue position 11 that mimics the stereoelectronic and conformational characteristics of the alpha-aminosuccinimide ring. In vitro, the gamma-lactam11 hGH-(6-13) peptide analog increased [14C]glucose incorporation into glycogen in muscles and conversion to lipid in adipose tissues. In vivo, the gamma-lactam11 hGH-(6-13) peptide enhanced hypoglycemia during iv insulin tolerance tests. The results demonstrate that the gamma-lactam11-hGH-(6-13) peptide analog has similar biological properties to the Asu11-hGH-(6-13) peptide fragment, but with improved molecular stability and bioavailability. PMID- 1639029 TI - Expression of the growth hormone receptor and growth hormone-binding protein during pregnancy in the mouse. AB - A 20-fold increase in the relative expression of the hepatic GH-binding protein (GHBP)-encoding message between nonpregnant and 17-day pregnant mice was found. The hepatic GH receptor (GHR)-encoding message increased 8-fold between nonpregnant and pregnant mice. The increase in both messages began on day 9 of pregnancy. The steady state level of the GHBP-encoding message continued to increase steadily until day 17 of pregnancy; however, by day 13 of pregnancy, the steady state level of the GHR-encoding message reached a plateau that continued to day 17. The ratio between the GHBP- and GHR-encoding messages gradually increased during the second half of pregnancy, reaching a maximum on day 17. There was a 10- to 16-fold increase in GH-binding capacity in liver microsomes and a 30- to 50-fold increase in serum GH-binding capacity between nonpregnant and late pregnant mice. The increase in hepatic GH-binding capacity began on day 9 of pregnancy and reached a plateau on day 11, which was maintained until the end of gestation. The increase in serum GH-binding capacity began on day 9 of pregnancy and continued to increase until day 17. No significant change in mouse (m) GHR (mGHR) or mGHBP affinity constants were observed between nonpregnant and pregnant mice; however, the mGHR had a 20-fold greater affinity for mGH than did the mGHBP. The serum GH concentration increased in the second half of pregnancy. The GHBP-bound and the free fractions of GH during pregnancy were predicted. While the bound fraction of GH is predicted to parallel the total GH concentration measured by RIA, the concentration of free mouse GH remains unchanged during pregnancy. PMID- 1639028 TI - Mullerian inhibiting substance messenger ribonucleic acid expression in granulosa and Sertoli cells coincides with their mitotic activity. AB - In males, Mullerian inhibiting substance (MIS) mRNA was first detected on the medial aspect of the urogenital ridge early on the morning of day 13 of gestation before testicular differentiation was evident, and localized to the more obvious Sertoli cells later on embryonic day 13. MIS transcripts remained at maximal levels between 14.5 and 17.5 days gestation, while the Mullerian duct involutes, and remained high until birth. MIS gene expression decreased progressively after birth and, as germ cell meiosis increased, became barely detectable in the Sertoli cells of the seminiferous tubules. In female rats, MIS mRNA was first detected in the single layer of cuboidal granulosa cells surrounding larger primary follicles 3 days after birth, coincident with the initiation of follicular growth. As follicular growth progressed, MIS mRNA expression was high in preantral and small antral follicles, especially in those granulosa cells closest to the oocyte. MIS mRNA expression decreased gradually in larger antral follicles, remaining prominent only in the cumulus cells and the dividing population of granulosa cells closest to the lumen. MIS gene expression was absent in follicles with features of atresia and in the larger antral follicles. The expression of MIS mRNA in actively dividing Sertoli and granulosa cells correlates with the stages of germ cell division. These findings are suggestive of a role for MIS in the control of germ cell maturation. PMID- 1639031 TI - Effect on insulin production sorting and secretion by major histocompatibility complex class II gene expression in the pancreatic beta-cell of transgenic mice. AB - Expression of major histocompatibility complex (MHC) class II protein in islet beta-cells of transgenic mice causes severe diabetes without an attendant autoimmune component. Little is known of the aberrant beta-cell function and site of biological lesions responsible for the diabetic state. Therefore, changes in (pro)insulin production, processing, sorting, storage, and secretion were evaluated using the in vitro perfused pancreas from male hyperglycemic BALB/cBYJ Tg (O pinsproA alpha d pinsproA beta d) mice and a RIA capable of detecting mouse insulin or proinsulin with quantitative equivalency. Results were compared to control pancreases from normal BALB/cBYJ mice. Extractable pancreatic insulin plus proinsulin content in the transgenics was 4% of normal. Normal pancreases responded characteristically with a diphasic insulin release during 30-min stimulation by glucose, a response that was enhanced by subsequent forskolin. In contrast, hormone release from transgenic pancreases was undetectable; based on the sensitivity of the immunoassay, fractional secretion of the residual pancreatic hormone content from the transgenic pancreases was less than 25% of normal. Proinsulin or insulin constitutive release was also not detected in the absence or presence of glucose-containing stimuli even when experiments were extended to 3 h. In contrast, fractional secretion in response to nonglucose stimuli (carbachol-leucine and arginine-leucine) was greater than normal from the transgenic diabetic pancreases. Responses to glucose stimuli did not normalize even after 90 min in the absence of glucose. In other experiments, pancreases were stimulated with carbachol/leucine/forskolin for 90 min, and the proportion of proinsulin to insulin released by the regulated pathway was determined after Sep-Pak and HPLC separation of combined eluates. Proinsulin was undetectable (and, therefore, accounted for less than 10% of the total hormone secretion). It is concluded from the observations of hyperglycemia, low pancreatic insulin content, and impaired release that insulin production in the pancreas of the MHC diabetic transgenic is severely depressed. The limited insulin production and chronic hyperglycemia do not (as speculated) cause missorting to a constitutive pathway or impaired conversion of proinsulin to insulin, since a proportionately increased proinsulin release does not occur. Although the response of the secretory process to glucose-containing stimuli is almost completely destroyed, fractional secretion in response to nonglucose stimuli is enhanced. The possible contribution of hyperglycemia-induced beta-cell desensitization or specific lesions in the glucose recognition signals induced by MHC expression are discussed. Results suggest that expression of MHC class II protein causes highly specific beta-cell lesions which, in themselves, could be a contributing factor in human insulin-dependent diabetes. PMID- 1639030 TI - Mechanism of action of estrogen on intramembranous bone formation: regulation of osteoblast differentiation and activity. AB - Dynamic bone histomorphometry, [3H]thymidine radioautography, and Northern analysis for bone matrix proteins and insulin-like growth factor-I (IGF-I) were performed in calvariae of ovariectomized (OVX) and estrogen-treated OVX rats. Treatment of OVX rats with diethylstilbestrol (DES) for 2 weeks reduced the periosteal mineral apposition rate, osteoblast number, and osteoblast size in calvarial periosteum. DES treatment also reduced the number of preosteoblasts in the S phase of the cell cycle, suggesting that the decrease in osteoblast number was due in part to inhibition of proliferation of osteoprogenitor cells. One week after ovariectomy, there were small increases in mRNA levels for pre pro-alpha 2 (I) subunit of type I collagen (collagen), osteocalcin, and osteonectin and a large increase in the mRNA level for IGF-I. DES treatment resulted in rapid decreases (3 h) in the mRNA levels for osteonectin, osteocalcin, and IGF-I. In contrast, mRNA levels for collagen were virtually unchanged after short term DES treatment. Uterus and liver served as positive and negative control tissues, respectively, for the effects of DES on IGF-I mRNA levels in OVX rats; mRNA levels were increased in uterus and decreased in liver after hormone treatment. We conclude from these studies that estrogen reduces periosteal bone formation by inhibiting both the differentiation and activity of osteoblasts. Furthermore, down-regulation of mRNA levels for IGF-I and bone matrix proteins precedes the changes in dynamic bone histomorphometry. PMID- 1639032 TI - Expression of epidermal growth factor (EGF) receptor and its ligands, EGF and transforming growth factor-alpha, in human fallopian tubes. AB - Although human uterus is known to contain epidermal growth factor (EGF) and its receptors, it is virtually unknown whether human fallopian tubes, which are an anatomical continuation of the uterus, also contain them. Therefore, the present studies investigated whether EGF and its structural and functional homolog, i.e. transforming growth factor-alpha (TGF-alpha), and their common receptor are expressed in human fallopian tubes. Human fallopian tubes contain major 10.5 kilobase (kb) and minor 6.0-kb receptor messenger RNA (mRNA) transcripts, a single 5.0-kb EGF mRNA transcript, and a single 170-kilodalton receptor protein. The transcripts, along with their corresponding proteins and TGF-alpha protein, are present in ciliated and nonciliated epithelial cells, tubal smooth muscle, vascular smooth muscle, and endothelium. The cellular distribution and reproductive state dependency of these three regulatory molecules varied. For all of them, however, ampullary segments contained more than isthmus; proliferative phase and/or postpartum specimens contained more than secretory phase; and postmenopausal specimens contained the lowest amounts. The cell periphery and nuclear/perinuclear area of the cells contained EGF, TGF-alpha, and their receptors. Immunogold electron microscopy showed the receptors to be present in cell membranes, cilia, basal bodies which control ciliary activity, endoplasmic reticulum, nuclear membranes, and chromatin. In summary, human fallopian tubes contain EGF, EGF/TGF-alpha receptor mRNA and protein, and TGF-alpha protein. The expression of all these regulatory molecules was dependent on anatomical region, cell type, and reproductive state of the fallopian tubes. These findings suggest that EGF and TGF-alpha may regulate numerous tubal functions, thus potentially influencing fertility in women. PMID- 1639033 TI - Quantification of vasoactive intestinal peptide immunoreactivity in the anterior pituitary glands of intact male and female, ovariectomized, and estradiol benzoate-treated rats. AB - There are considerable data suggesting that vasoactive intestinal peptide (VIP) is involved in the regulation of PRL secretion; however, the role and cell of origin of anterior pituitary VIP remain to be determined. Immunocytochemical (ICC) studies have generally failed to detect VIP-immunoreactive (IR) cells in the pituitary of the untreated rat, although VIP-IR cells have been observed in the pituitaries of hypothyroid or estrogen-treated rats. This study was designed to examine the cellular distribution and tissue content of VIP in the anterior pituitary gland of rats under selected endocrine conditions known to alter the rates of PRL and VIP synthesis and secretion. To this end, anterior pituitary VIP and PRL content (ICC and RIA) and serum PRL levels were determined in ovariectomized (OVX) and OVX rats 3 days after treatment with 7 or 70 micrograms estradiol benzoate (EB). For comparison, pituitary VIP and PRL content (ICC and RIA) and serum PRL levels in untreated male and diestrous female rats were determined. Immunostaining for VIP was accomplished using a newly developed primary antiserum. Significant numbers of VIP-IR cells per 5-microns section were found in the anterior pituitary glands of all animals examined (275 +/- 33 in diestrous to 481 +/- 103 cells in male rats). VIP was not colocalized with PRL in any of the pituitaries regardless of steroid treatment or sex. Furthermore, the number of VIP-IR cells per pituitary gland was not significantly correlated with sex or EB treatment. Treatment with 70 micrograms, but not 7 micrograms, EB significantly increased the pituitary content of VIP and serum PRL levels compared to those after ovariectomy. However, both EB treatments resulted in a significant increase in pituitary PRL content compared to that in untreated OVX rats. Pituitaries from male rats had several-fold more VIP and less PRL content than pituitaries from diestrous rats. These data show that 1) in contrast to previous ICC studies, VIP-IR cells are readily detected in the anterior pituitary of intact male and female and OVX as well as EB-treated rats; 2) VIP is localized to cells other than lactotrophs, regardless of the steroid background; and 3) marked changes in anterior pituitary VIP content are not accompanied by changes in VIP-IR cell number. PMID- 1639034 TI - Tissue-specific distribution of the NAD(+)-dependent isoform of 11 beta hydroxysteroid dehydrogenase. AB - 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) converts the active glucocorticoid corticosterone to inactive 11-dehydrocorticosterone in rat (or cortisol to cortisone in man), thereby protecting renal mineralocorticoid receptors from corticosterone or cortisol and allowing preferential access for aldosterone. Recent work suggests that a nicotinamide adenine dinucleotide (NAD+) dependent 11 beta-OHSD isoform is expressed in distal renal tubule, in contrast with the hepatic isoform which is NAD(+)-phosphate (NADP+)-dependent. To establish the distribution of the NAD(+)-dependent isoform we measured in vitro conversion of [3H]corticosterone to [3H]11-dehydrocorticosterone in homogenized rat tissues in the presence of NADP+ or NAD+. In most tissues (liver, testis, hippocampus, heart, aorta, mesenteric artery) NADP+ increased activity and NAD+ was without effect. However, in whole renal cortex, colon, placenta, and lung both NADP+ and NAD+ increased activity. No difference in cofactor utilization was demonstrated between proximal and distal renal tubules following density gradient separation. This distribution of NAD(+)-dependent activity corresponds with: (i) the distribution of multiple mRNA and/or protein species of 11 beta-OHSD; (ii) the distribution of aldosterone-specific mineralocorticoid receptors; and (iii) the equilibrium between active and inactive glucocorticoids in each tissue. We suggest that the tissue-specific expression of isoforms of 11 beta-OHSD with different kinetic properties confers on them diverse roles in modulating corticosteroid receptor activation. PMID- 1639035 TI - Evidence for a rapid stimulation of tyrosine kinase activity by prolactin in Nb2 rat lymphoma cells. AB - Studies were designed to determine if the activation of tyrosine kinases may be involved in the signal transduction pathway for PRL. Tyrosyl phosphorylation of cellular proteins was evaluated by western blot analysis of Nb2 cell proteins employing an antibody to phosphotyrosine. Physiological concentrations of ovine PRL (oPRL) had a pronounced effect on the tyrosyl phosphorylation of a 121 kDa protein. Increased tyrosyl phosphorylation of the 121 kDa protein was detectable with concentrations of oPRL as low as 0.5 ng/ml. Consistent with oPRL acting through a PRL receptor, hGH also stimulated tyrosyl phosphorylation of the 121 kDa protein when tested at concentrations between 5 and 20 ng/ml. In time course experiments, increased tyrosyl phosphorylation of the 121 kDa protein was apparent after a 5 min incubation with 20 ng/ml hGH, and maintained for at least one h. At higher concentrations of hGH (200 ng/ml), increased phosphorylation of the 121 kDa protein was clearly evident after only 1 min, indicating that tyrosyl phosphorylation of cellular proteins is an early event following ligand binding to the PRL receptor. Increased tyrosyl phosphorylation of proteins of 40, 90 and 55-65 kDa was also evident after incubation with hGH for 10, 10, and 60 min respectively. These findings are consistent with PRL-dependent tyrosine kinase activation being an early and perhaps initiating event in the signal transduction pathway for PRL in Nb2 cells. PMID- 1639036 TI - Hypothyroidism increases vasoactive intestinal polypeptide (VIP) immunoreactivity and gene expression in the rat hypothalamic paraventricular nucleus. AB - Vasoactive intestinal polypeptide (VIP) is produced by neurons in the rat hypothalamic paraventricular nucleus (PVN) and may have an important role as a prolactin-releasing factor. Recent work from our laboratories has shown that thyroid hormone regulates the content of VIP and VIP mRNA in the rat anterior pituitary, but its effect on VIP in the PVN is not known. To determine whether thyroid hormone alters VIP biosynthesis in the PVN, we studied the effect of hypothyroidism on the content of immunoreactive (IR)-VIP and VIP mRNA in PVN neurons using histochemical techniques. By immunocytochemistry, only scattered IR VIP fibers were present in the PVN of control animals whereas IR-VIP perikarya and fibers were present in hypothyroid rats. By in situ hybridization histochemistry, no labeled neurons were recognized in the PVN in control animals whereas PVN neurons were labeled in hypothyroid rats. These findings raise the possibility that hypothyroidism exerts negative feedback regulation on VIP producing neurons in the PVN and suggest that this may be important to modulate the stimulatory effects of VIP on anterior and/or posterior pituitary function. PMID- 1639037 TI - Transcriptional regulation of prolactin receptor gene expression by sodium butyrate in MCF-7 human breast cancer cells. AB - The prolactin receptor (PRLR) mediates the diverse effects of prolactin, which in the mammary gland include the development of lobuloalveolar structures and increased tumor cell proliferation. Treatment of mammary carcinoma cells with the differentiating agent sodium butyrate (NaB) is known to reduce PRLR binding activity and PRLR gene expression, however the mechanism which mediates these changes is unknown, prompting this investigation. Using MCF-7 human breast cancer cells, assay of the rate of PRLR gene transcription by the nuclear run-on technique indicated that 3 mM NaB reduced PRLR gene transcription by 50% after 3 h of treatment and that this effect was maintained for at least 24 h. The protein synthesis inhibitor cycloheximide failed to abrogate this effect, which indicated that NaB did not require continuing protein synthesis to reduce the rate of PRLR transcription. Measurement of PRLR mRNA stability, using Northern blot analysis at various times after the inhibition of transcription with actinomycin D, showed that NaB treatment did not alter PRLR mRNA half-life. These results indicate that NaB inhibits PRLR gene expression by a transcriptional mechanism that does not require continuing protein synthesis. PMID- 1639038 TI - Citation for the Ernst Oppenheimer Award of the Endocrine Society to James Larry Jameson. PMID- 1639039 TI - Citation for the Richard E. Weitzman Memorial Award to Fred E. Cohen. PMID- 1639040 TI - Citation for the Fred Conrad Koch Award of the Endocrine Society to Melvin M. Grumbach and Selna L. Kaplan. PMID- 1639041 TI - Citation for the Edwin B. Astwood Lectureship of the Endocrine Society to Michael O. Thorner. PMID- 1639042 TI - Citation for the Sidney H. Ingbar Distinguished Service Award to Nettie Karpin. PMID- 1639043 TI - Citation for the Robert H. Williams Distinguished Leadership Award to Claude J. Migeon. PMID- 1639044 TI - Citation for the Rhone-Poulene Rorer Pharmaceutical Clinical Investigator Award of the Endocrine Society to Samuel S.C. Yen. PMID- 1639045 TI - Effect of diet on glucose tolerance 36 hours after glycogen-depleting exercise. AB - In order to estimate the effect of muscle glycogen content on the glycaemic response, glucose tolerance and glucose oxidation were measured in eight healthy male subjects. Each subject followed three different treatments, consisting of either a physical exercise session followed by 36 h of a low-carbohydrate high fat diet (glycogen depletion treatment); or a physical exercise followed by 36 h of a high carbohydrate diet (glycogen repletion treatment); or a low-carbohydrate high-fat diet alone (diet treatment). After both the glycogen depletion and the diet treatments, the subjects showed a high glycaemic response (443 +/- 57 and 419 +/- 63 mmol.min/l resp.), a high insulinaemic response (7158 +/- 671 and 7643 +/- 913 mU.min/l), and a low rate of glucose oxidation (27.5 +/- 2.4 and 31.0 +/- 5.8 g/3 h respiration). In contrast, after the glycogen repletion treatment, the subjects had a lower glycaemic response (197 +/- 21 mmol.min/l), a lower insulinaemic response (4645 +/- 327 mU.min/l) and a higher glucose oxidation level (47.4 +/- 2.0 g/3h). Fasting free fatty acids (FFA) were positively correlated with glucose area (P less than 0.001) and negatively with glucose oxidation (P less than 0.01). These results show a strong inhibitory effect of the low-carbohydrate high-fat diet on glucose tolerance despite prior strenuous exercise. Because of this, the effect of the muscle glycogen content could not be tested. However, the results suggest that the FFA/glucose interrelationship may override exercise-induced changes in insulin-stimulated glucose uptake. PMID- 1639046 TI - Dietary intervention in breast cancer patients: effects on food choice. AB - Effects of dietary intervention on food choice were studied in 240 women aged 50 65 years who had been operated for a stage I-II breast cancer. Following surgery, the women participated in a dietary history interview and were then randomized to one of two groups. The intervention group (n = 121) received individual dietary counselling aimed at reducing dietary fat intake to 20-25% energy (E%), whereas no dietary advice was given to women in the control group (n = 119). For the 52% of the women in the intervention group that completed the study the total fat intake decreased from 36 to 23 E% (P less than or equal to 0.01) and from 37 to 34 E% (P less than or equal to 0.01) for the control group. There were significant reductions in the intake of table fat, high-fat milk products, pork and sausages (containing greater than 11% fat), eggs, rice, pasta, cakes and chocolate for the intervention group. Concurrently the intake of vegetables, fruits, potatoes, bread, cereals, low-fat milk products, low-fat meat, sausages and fish increased significantly. For the control group there was a significant decrease in the consumption of total milk products, total meats, rice, pasta, cakes, and butter intake while the consumption of vegetables, fruits, cereals and fish increased (P less than or equal to 0.01). Reduction of high-fat foods and increases of carbohydrate-rich foods were more pronounced for the intervention group than for the control group. Formal education influenced dietary changes, and dietary counselling should therefore ideally be adapted to education level. This study showed that dietary counselling can bring about significant changes in consumption of high-fat foods for at least a 2-year period for women operated for breast cancer. PMID- 1639047 TI - Salmon diet and human immune status. AB - We examined the effect of feeding a salmon-containing diet on the immune status of nine healthy men (age 30-65 years) who lived at the metabolic suite of the Western Human Nutrition Research Center for 100 days. During the first 20 days all nine subjects consumed a basal diet (BD). For the next 40 days, three subjects continued to consume BD, while the diet of remainder six subjects was modified to contain 500 g salmon every day. During the last 40 days, the diets of the two groups were crossed over. Feeding 500 g salmon daily for 40 days did not significantly suppress the blastogenesis of peripheral blood mononuclear cells cultured with phytohemagglutinin, Concanavalin A, protein A or pokeweed when compared to the corresponding pre-salmon diet values. It also did not significantly affect the delayed hypersensitivity skin response to seven recall antigens, serum concentrations of immunoglobulins G, M, and A, and complement fractions C3 and C4. Our results indicate that the short-term consumption of a high fish (salmon)-containing diet does not adversely affect the immune system, as has been reported with fish oil supplements. PMID- 1639048 TI - Urea kinetics: comparison of oral and intravenous dose regimens. AB - Urea kinetics were measured on two separate occasions in five adults with normal haemoglobin genotype (HbAA) and in four who were homozygous for sickle cell disease (HbSS). Prime/intermittent doses of [15N15N]urea were given orally on one occasion and intravenously on the other. In three of the nine individuals there appeared to be significant hydrolysis of the oral dose of urea before absorption, leading to spurious results for the urea kinetics. When only the studies in which isotope was given intravenously were considered, there was a difference in the rate at which urea-N was salvaged, with more urea-N being salvaged by HbSS subjects than HbAA. It is concluded that the oral presentation of isotope can be used to measure urea kinetics provided care is taken to exclude those subjects who are likely to display upper intestinal hydrolysis, and that there are differences in aspects of urea kinetics between HbAA and HbSS which may be of metabolic importance. PMID- 1639049 TI - Protein turnover in pregnancy. AB - Whole-body protein metabolism was studied at 13, 24 and 35 weeks gestation in six healthy women using a continuous infusion [13C]leucine technique. Values were expressed in terms of fat-free body weight (FFM) calculated using literature standards for changes in total body potassium during pregnancy. Mean protein synthesis increased from 5.3 (+/- 0.6 SD) g/kg FFM/24h at 13 weeks to 5.9 +/- 0.5 (P less than 0.1) at 24 weeks and 6.1 +/- 0.6 at 35 weeks (P less than 0.05 vs 3 weeks). Similar increases were noted in catabolism so that net loss changed little. Protein synthesis at 24 and 35 weeks gestations was significantly greater than that in 17 healthy, non-pregnant women (4.9 +/- 0.6, P less than 0.001). These data indicate that there are substantial increases in protein turnover during pregnancy. PMID- 1639050 TI - Body mass index, body composition and the chronic energy deficiency classification of rural adult populations in Guatemala. AB - The present study tested the hypotheses that: (a) individual body composition estimates obtained with the Durnin-Womersley (D-W) equations have low validity in certain populations in developing countries; (b) there exists a poor relationship between the body mass index (BMI) and body composition estimates (fat mass (BFM) and fat-free mass (FFM)), and (c) BMI cut-off estimates (fat mass (BFM) and fat free mass (FFM)), and (c) BMI cut-off points provide an invalid classification of chronic energy deficiency (CED) in adults. The study involved four samples of rural men and women in Guatemala, who had mean BMI of approximately 21 kg/m2. Body composition estimates were obtained by densitometry in three of the samples. Mean body fat (%) and mean FFM (kg) were: men: 11.6 (+/- 4.7) and 47.7 (+/- 4.9); and women: 21.6 (+/- 5.3) and 35.8 (+/- 3.5), respectively. The D-W equations based on various combinations of skinfold measurements consistently overestimated body fat content with low precision and validity. The BMI was more related to BFM and FFM than to fat proportion, but explained little of the variation in both body components, particularly at low BMI levels. A small number of men and women had BMI values below 18.5 kg/m2, and only one woman fell below 16 kg/m2. The power coefficients of height in the weight/height ratio which provided the strongest correlations with BFM and FFM were: BFM: women: 1.0; men: 1.5; FFM: 0.5 for both women and men. We conclude that the Quetelet index should not be recommended as a universally valid indicator to classify CED in adult groups similar to the study population. PMID- 1639051 TI - Should mono- or poly-unsaturated fats replace saturated fat in the diet? AB - The effects of diets differing in saturated, monounsaturated and polyunsaturated fatty acid composition (SAFA, MUFA and PUFA, respectively) on plasma lipoproteins and factor VIIc were investigated in 28 middle-aged men and women with mild to moderate hyperlipidaemia. The subjects were stabilized on a diet with a total fat content fairly typical of New Zealand, containing approximately 40% energy as fat, before entering a randomized cross-over trial of diets high in PUFA (20% energy; SAFA and MUFA 10% each) or a high MUFA diet (20% energy; SAFA and PUFA 10% each). After 6-week periods on each diet the subjects returned to a high SAFA diet. Body weight and blood pressure remained unchanged during the study. Total and LDL cholesterol, HDL cholesterol and the HDL2 subfraction were significantly lower on both the MUFA and the PUFA diet than on SAFA. However, there were no statistically significant differences in lipoprotein concentrations on the MUFA and PUFA diet. Factor VIIc concentrations were similar on the three diets. The proportion of PUFA in a MUFA diet appears to be a major determinant of the relative lipoprotein response to such a diet. In order to avoid a reduction in HDL-C when replacing SAFA with MUFA it may be necessary to ensure that PUFA does not provide more than about 8% total energy. Thus careful planning is needed to identify the most appropriate foods to replace those rich in SAFA in diets designed to reduce the lipoprotein-mediated risk of coronary heart disease. PMID- 1639052 TI - Lack of therapeutic efficacy of vitamin A for non-cholera, watery diarrhoea in Bangladeshi children. AB - Vitamin A deficiency has been postulated to increase childhood mortality, possibly through increasing the severity and case-fatality of infectious diseases like diarrhoea. A clinical trial was conducted to measure the effect of vitamin A therapy on the severity and duration of acute episodes of non-cholera, watery diarrhoea; 83 children with less than 48 h of illness were randomized to receive vitamin A (200,000 IU of retinyl palmitate) orally or placebo during hospitalization at the International Centre for Diarrhoeal Disease Research in Bangladesh. The patients were similar initially with regard to age, nutritional status and severity of diarrhoea prior to admission. No adverse effects of vitamin A were detected. During hospitalization there were no differences between groups in duration of illness or stool output. Thus, vitamin A can be given safely during diarrhoeal illness to augment hepatic reserves and possibly provide a beneficial effect in regard to subsequent episodes of diarrhoea and other infections, but this supplementation should not be expected to have a therapeutic effect on a current episode. PMID- 1639053 TI - Supplementation with selenium-rich bread does not influence platelet aggregation in healthy volunteers. AB - In order to establish the effect of an increased dietary selenium supply on platelet glutathione peroxidase (EC 1.11.1.9.; GSH-Px) and platelet aggregation, six healthy subjects were supplemented with 200 micrograms Se as Se-rich bread for 6 weeks. Another six subjects received low-Se bread and served as controls. Platelet GSH-Px activity increased significantly in the supplementation group, whereas no effect could be observed on platelet aggregation. The results of this study do not support the hypothesis that an increased dietary Se intake has a favourable influence on platelet aggregation. PMID- 1639054 TI - Tumour regression following chemotherapy does not increase food intake. AB - Forty-six patients with cancer of the breast, ovary or lung (small cell) were followed for 5 months after initiation of cyclical chemotherapy to examine if any changes in voluntary food intake or nutritional status were related to treatment response. The study showed a slight decrease in protein (P less than 0.05) and energy intake (not significant) at 3 months compared to pretreatment intakes in 31 patients with objective tumour regression. In 15 non-responding patients no changes were demonstrated. There were no changes in anthropometric status related to treatment response. Despite the lower protein intake in treatment responders p albumin increased significantly compared to pretreatment value. Thus, initially successful chemotherapeutic treatment is not automatically followed by improved nutrition, and many of these patients are potential candidates for early dietary intervention. PMID- 1639055 TI - Studies on the expression of the pufX polypeptide and its requirement for photoheterotrophic growth in Rhodobacter sphaeroides. AB - The puf operon in Rhodobacter sphaeroides contains the genes for the light harvesting antenna complex I (LHI), the reaction centre (RC) L and M subunits and an additional small open reading frame identified as pufX. It has been demonstrated before that a photosynthetically incompetent pufLMX deletion strain was not complemented by a plasmid-borne truncated puf operon version lacking only pufX, although expression of the pufL and pufM gene products was restored. We demonstrate here that the functional reinsertion of only the pufX open reading frame into the same construct is sufficient and necessary for complementation of the non-photosynthetic phenotype. We also demonstrate that the observed lack of photoheterotrophic growth in the absence of pufX is not the result of decreased light-harvesting ability, but rather the result of an impairment in light-driven cyclic electron transfer. Western blots using polyclonal antibodies against a synthetic peptide corresponding to a portion of the DNA-derived pufX amino acid sequence showed that the pufX open reading frame is expressed and that the gene product has an M(r) of 8-10,000 on SDS gels; a value close to the predicted mass of 9 kDa. The pufX polypeptide was localized to the intracytoplasmic membrane fraction and appeared to co-purify with the RC-LHI complex. It is suggested that the pufX polypeptide is associated with the RC-LHI complex and that it may play a critical role in facilitating the interaction between this complex and other components required for light-driven cyclic electron transfer. PMID- 1639056 TI - A role for clathrin in the sorting of vacuolar proteins in the Golgi complex of yeast. AB - We have investigated the role of clathrin in vacuolar protein sorting using yeast strains harboring a temperature-sensitive allele of clathrin heavy chain (chc1 ts). After a 5 min incubation at the non-permissive temperature (37 degrees C), the chc1-ts strains displayed a severe defect in the sorting of lumenal vacuolar proteins. Sorting of a vacuolar membrane protein, alkaline phosphatase, and transport to the surface of a cell wall protein, was not affected at 37 degrees C. In chc1-ts cells incubated at 37 degrees C, secretion of the missorted lumenal vacuolar protein carboxypeptidase Y (CPY) was blocked by the sec1 mutation which prevents fusion of secretory vesicles to the plasma membrane. Unexpectedly, chc1 ts cells incubated for extended periods at 37 degrees C regained the ability to sort CPY. Cells carrying deletions of the CHC1 gene (chc1 delta) also sorted CPY to the vacuole even when subjected to temperature shifts. Vacuolar delivery of CPY in chc1 delta cells was not blocked by sec1 suggesting that transport does not occur by secretion and endocytosis. These results provide in vivo evidence that clathrin plays a role in the Golgi complex in sorting of vacuolar proteins from the secretory pathway. With time, however, yeast cells lacking functional clathrin heavy chains are able to adapt in a way that allows restoration of vacuolar protein sorting in the Golgi complex. These conclusions clarify previous studies of chc1 delta cells which raised the possibility that clathrin is not involved in vacuolar protein sorting. PMID- 1639057 TI - Signal peptidase I of Bacillus subtilis: patterns of conserved amino acids in prokaryotic and eukaryotic type I signal peptidases. AB - Signal peptidases (SPases) remove signal peptides from secretory proteins. The sipS (signal peptidase of subtilis) gene, which encodes an SPase of Bacillus subtilis, was cloned in Escherichia coli and was also found to be active in E.coli. Its overproduction in B.subtilis resulted in increased rates of processing of a hybrid beta-lactamase precursor. The SipS protein consisted of 184 amino acids (mol. wt 21 kDa). The protein showed sequence similarity with the leader peptidases of E.coli and Salmonella typhimurium, and the mitochondrial inner membrane protease I of Saccharomyces cerevisiae. Patterns of conserved amino acids present in these four proteins were also detected in the Sec11 subunit of the SPase complex of S.cerevisiae and the 18 and 21 kDa subunits of the canine SPase complex. Knowledge of the sequence of SipS was essential for the detection of these similarities between prokaryotic and eukaryotic SPases. The data suggest that these proteins, which have analogous functions, belong to one class of enzymes, the type I SPases. PMID- 1639058 TI - Stable surface expression of invariant chain prevents peptide presentation by HLA DR. AB - Class II major histocompatibility complex (MHC) molecules are cell surface glycoproteins that bind and present immunogenic peptides to T cells. Intracellularly, class II molecules associate with a polypeptide referred to as the invariant (Ii) chain. Ii is proteolytically degraded and dissociates from the class II complex prior to cell surface expression of the mature class II alpha beta heterodimer. Using human fibroblasts transfected with HLA-DR1 and Ii cDNAs, we now demonstrate that truncation of the cytoplasmic domain of Ii results in the failure of Ii to dissociate from the alpha beta Ii complex and leads to stable expression of class II alpha beta Ii complexes on the cell surface. Furthermore, biochemical analysis and peptide presentation assays demonstrated that transfectants with stable surface alpha beta Ii complexes expressed very few free alpha beta heterodimers at the surface and were very inefficient in their ability to present immunogenic peptides to T cells. These results support the hypothesis that the cytoplasmic domain of Ii is responsible for endosomal targeting of alpha beta Ii and directly demonstrate that association with Ii interferes with the antigen presentation function of class II molecules. PMID- 1639059 TI - RAS residues that are distant from the GDP binding site play a critical role in dissociation factor-stimulated release of GDP. AB - We have previously shown that a conserved glycine at position 82 of the yeast RAS2 protein is involved in the conversion of RAS proteins from the GDP- to the GTP-bound form. We have now investigated the role of glycine 82 and neighbouring amino acids of the distal switch II region in the physiological mechanism of activation of RAS. We have introduced single and double amino acid substitutions at positions 80-83 of the RAS2 gene, and we have investigated the interaction of the corresponding proteins with a yeast GDP dissociation stimulator (SDC25 C domain). Using purified RAS proteins, we have found that the SDC25-stimulated conversion of RAS from the GDP-bound inactive state to the GTP-bound active state was severely impaired by amino acid substitutions at positions 80-81. However, the rate and the extent of conversion from the GDP- to the GTP-bound form in the absence of dissociation factor was unaffected. The insensitivity of the mutated proteins to the dissociation factor in vitro was paralleled by an inhibitory effect on growth in vivo. The mutations did not significantly affect the interaction of RAS with adenylyl cyclase. These findings point to residues 80-82 as important determinants of the response of RAS to GDP dissociation factors. This suggests a molecular model for the enhancement of nucleotide release from RAS by such factors. PMID- 1639060 TI - Identification of the binding interface involved in linkage of cytoskeletal protein 4.1 to the erythrocyte anion exchanger. AB - Linkages of the cytoskeleton to integral membrane proteins of the plasma membrane have been shown to be important for diverse cellular functions. The erythrocyte membrane provides the best studied example of how the spectrin-actin based membrane cytoskeleton is linked via two proteins, ankyrin and protein 4.1, to the anion exchanger (anion exchanger 1, AE1). Although these and other types of cytoskeleton-membrane connections have been well documented by in vitro binding studies it has not been possible to establish any of such interactions by defining the binding interface at the amino acid level. In the present study we have performed binding studies between protein 4.1 and AE1 using peptides and corresponding idiotypic and anti-idiotypic antibodies to show that arginine-rich clusters of the cytoplasmic domain of AE1 (IRRRY/LRRRY) serve as a major binding site for a motif with opposite charge and identical hydrophobicity present on the membrane-binding domain of protein 4.1 (LEEDY). Both motifs appear to be highly conserved during evolution and may also be involved in other types of cytoskeleton-membrane association, i.e. in binding of protein 4.1 to the glycophorins. PMID- 1639061 TI - Cytoplasmic calcium transients due to single action potentials and voltage-clamp depolarizations in mouse pancreatic B-cells. AB - Changes in the cytoplasmic free calcium concentration ([Ca2+]i) in pancreatic B cells play an important role in the regulation of insulin secretion. We have recorded [Ca2+]i transients evoked by single action potentials and voltage-clamp Ca2+ currents in isolated B-cells by the combination of dual wavelength emission spectrofluorimetry and the patch-clamp technique. A 500-1000 ms depolarization of the B-cell from -70 to -10 mV evoked a transient rise in [Ca2+]i from a resting value of approximately 100 nM to a peak concentration of 550 nM. Similar [Ca2+]i changes were associated with individual action potentials. The depolarization induced [Ca2+]i transients were abolished by application of nifedipine, a blocker of L-type Ca2+ channels, indicating their dependence on influx of extracellular Ca2+. Following the voltage-clamp step, [Ca2+]i decayed with a time constant of approximately 2.5 s and summation of [Ca2+]i occurred whenever depolarizations were applied with an interval of less than 2 s. The importance of the Na(+)-Ca2+ exchange for B-cell [Ca2+]i maintenance was evidenced by the demonstration that basal [Ca2+]i rose to 200 nM and the magnitude of the depolarization-evoked [Ca2+]i transients was markedly increased after omission of extracellular Na+. However, the rate by which [Ca2+]i returned to basal was not affected, suggesting the existence of additional [Ca2+]i buffering processes. PMID- 1639062 TI - The mec-7 beta-tubulin gene of Caenorhabditis elegans is expressed primarily in the touch receptor neurons. AB - Mutants of the mec-7 beta-tubulin gene of Caenorhabditis elegans lack the large diameter 15-protofilament microtubules normally found only in the set of six touch receptor neurons. Both a mec-7-lacZ reporter gene and affinity-purified anti-mec-7 antibodies were used to show that mec-7 is expressed primarily in the touch neurons. These data are consistent with a possible instructive role for the mec-7 tubulin in determining microtubule protofilament number. The antibodies and the mec-7-lacZ transgene were also used to examine mec-7 expression in mutants affecting the generation, differentiation or maintenance of the touch neurons. Decreased expression was observed in mutants of unc-86 and mec-3, genes that encode transcription factors essential for touch receptor neuron generation and differentiation, respectively. PMID- 1639063 TI - A family of human cdc2-related protein kinases. AB - The p34cdc2 protein kinase is known to regulate important transitions in the eukaryotic cell cycle. We have identified 10 human protein kinases based on their structural relation to p34cdc2. Seven of these kinases are novel and the products of five share greater than 50% amino acid sequence identity with p34cdc2. The seven novel genes are broadly expressed in human cell lines and tissues with each displaying some cell type or tissue specificity. The cdk3 gene, like cdc2 and cdk2, can complement cdc28 mutants of Saccharomyces cerevisiae, suggesting that all three of these protein kinases can play roles in the regulation of the mammalian cell cycle. The identification of a large family of cdc2-related kinases opens the possibility of combinatorial regulation of the cell cycle together with the emerging large family of cyclins. PMID- 1639064 TI - The human p50csk tyrosine kinase phosphorylates p56lck at Tyr-505 and down regulates its catalytic activity. AB - Protein tyrosine kinases participate in the transduction and modulation of signals that regulate proliferation and differentiation of cells. Excessive or deregulated protein tyrosine kinase activity can cause malignant transformation. The catalytic activity of the T cell protein tyrosine kinase p56lck is normally suppressed by phosphorylation of a carboxyl-terminal tyrosine, Tyr-505, by another cellular protein tyrosine kinase. Here we characterize a human cytosolic 50 kDa protein tyrosine kinase, p50csk, which specifically phosphorylates Tyr-505 of p56lck and a synthetic peptide containing this site. Phosphorylation of Tyr 505 suppressed the catalytic activity of p56lck. We suggest that p50csk negatively regulates p56lck, and perhaps other cellular src family kinases. PMID- 1639065 TI - Activation of mammalian DNA ligase I through phosphorylation by casein kinase II. AB - Mammalian DNA ligase I has been shown to be a phosphoprotein. Dephosphorylation of purified DNA ligase I causes inactivation, an effect dependent on the presence of the N-terminal region of the protein. Expression of full-length human DNA ligase I in Escherichia coli yielded soluble but catalytically inactive enzyme whereas an N-terminally truncated form expressed activity. Incubation of the full length preparation from E. coli with purified casein kinase II (CKII) resulted in phosphorylation of the N-terminal region and was accompanied by activation of the DNA ligase. Of a variety of purified protein kinases tested, only CKII stimulated the activity of calf thymus DNA ligase I. Tryptic phosphopeptide analysis of DNA ligase I revealed that CKII specifically phosphorylated a major peptide also apparently phosphorylated in cells, implying that CKII is a protein kinase acting on DNA ligase I in the cell nucleus. These data suggest that DNA ligase I is negatively regulated by its N-terminal region and that this inhibition can be relieved by post-translational modification. PMID- 1639066 TI - Mobile nucleosomes--a general behavior. AB - We have previously reported the mobility of positioned nucleosomes on sea urchin 5S rDNA. In this study we demonstrate the temperature dependence and the range of this mobility on 5S rDNA constructs. We find that this dynamic behavior also applies to bulk mononucleosomes and nucleosomes reconstituted onto sequences of the Alu family of ubiquitous repeats. We conclude that short range sliding is potentially a general phenomenon that is dependent on the underlying sequence and its position on the histone octamer. The nucleoprotein gel analysis used also reveals the dramatic effect on gel electrophoretic migration caused by the location of the histone octamer on DNA fragments. The usefulness of this technique for studying nucleosome positioning and its dynamics is demonstrated. PMID- 1639067 TI - Identification of a stage selector element in the human gamma-globin gene promoter that fosters preferential interaction with the 5' HS2 enhancer when in competition with the beta-promoter. AB - The erythroid-specific enhancer within hypersensitivity site 2 (HS2) of the human beta-globin locus control region is required for high level globin gene expression. We investigated interaction between HS2 and the gamma- and beta promoters using reporter constructs in transient assays in human erythroleukemia (K562) cells. The beta-promoter, usually silent in K562 cells, was activated by HS2. This activity was abolished when a gamma-promoter was linked in cis. Analysis of truncation mutants suggested that sequences conveying the competitive advantage of the gamma-promoter for HS2 included those between positions -53 and 35 relative to the transcriptional start site. This sequence, when used to replace the corresponding region of the beta-promoter, increased beta-promoter activity 10-fold when linked to HS2. The modified beta-promoter was also capable of competing with a gamma-promoter modified internally in the -53 to -35 region, when the two promoters were linked to HS2 in a single plasmid. The corresponding sequences from the Galago gamma-promoter, a species which lacks fetal gamma-gene expression, were inactive in analogous assays. We have identified and partially purified a nuclear protein found in human (fetal stage) erythroleukemia cells, but present in much lower concentration in murine (adult stage) erythroleukemia cells, that binds the -53 to -35 sequence of the gamma-promoter. We speculate that this region of the gamma-promoter functions as a stage selector element in the regulation of hemoglobin switching in humans. PMID- 1639068 TI - Cell-specific transcription of the peripherin gene in neuronal cell lines involves a cis-acting element surrounding the TATA box. AB - Peripherin is a neurone-specific intermediate filament protein expressed mostly in the peripheral nervous system. To localize sequences that are important for the regulation of peripherin gene transcription, we have functionally dissected its promoter. Transfection into different cell lines and deletion mapping of peripherin-lacZ hybrid constructs indicated that the first 98 bp preceding the transcription start site of the gene were sufficient to confer cell-type specific expression. DNase I footprinting experiments revealed three protected sequences in this region, that were named PER1, PER2 and PER3. The PER2 and PER3 elements, localized between -98 to -46, interact with proteins that seem widely distributed. Deletion of these elements severely decreased the level of reporter gene activity. The PER1 element, which overlaps the TATA box, interacts with a DNA-binding protein prevailing in peripherin expressing cell lines. However, the core promoter, which contains the PER1 element, was inefficient in driving gene expression. Experiments designed to test the contribution of each element showed that PER2 and PER3 were important in determining the level of expression, while PER1 was important for cell-type specificity. In fact the polyoma virus enhancer linked to the peripherin gene core promoter was found to limit reporter gene activity to peripherin expressing cell lines. Together, these experiments indicate that co-operative interactions between different regions of the promoter are necessary for efficient and cell-type specific transcription of the peripherin gene in a subset of neuronal cells. PMID- 1639069 TI - Hepatitis B virus transactivator MHBst: activation of NF-kappa B, selective inhibition by antioxidants and integral membrane localization. AB - C-terminal truncation of the middle surface antigen from hepatitis B virus (MHBs) gives rise to a novel transactivating protein, called MHBst. In this study we show that MHBst like the HBx protein of HBV, can cause nuclear appearance of NF kappa B DNA binding activity and induce various kappa B-controlled reporter genes. While an inhibitor of protein kinase C could not block gene induction by MHBst, the antioxidants N-acetyl-L-cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC) could potently suppress transactivation at mM and microM concentrations, respectively. Also, kappa B-dependent gene induction by the transactivator HBx was blocked. The effects were selective because PDTC did not interfere with MHBst and HBx-induced activation of the c-fos promoter/enhancer, nor with the basal activity of several other reporter genes lacking functional NF-kappa B binding motifs. Our data suggest that induction of a prooxidant state is crucial for the activation of NF-kappa B by MHBst and HBx and might be related to the hepatocarcinogenic potential of the viral proteins. MHBst had a subcellular localization unusual for a viral transactivator: it appeared to be an integral membrane protein of the endoplasmic reticulum. PMID- 1639070 TI - The NF-kappa B p50 precursor, p105, contains an internal I kappa B-like inhibitor that preferentially inhibits p50. AB - The p50 subunit of NF-kappa B is apparently synthesized as a precursor molecule of 105 kDa (p105); subsequent processing releases the amino-terminal p50 polypeptide with rel homology, DNA binding activity and transcriptional activation potential. The carboxy-terminal region of p105 contains seven copies of an ankyrin-related sequence previously found in several genes involved in differentiation and cell cycle control. Two proteins with I kappa B activity, MAD 3 and pp40, have been cloned and found to contain five obvious ankyrin repeats that align with those in the carboxy-terminus of p105. Both proteins target their inhibitory activity to the p65 subunit of NF-kappa B and to c-rel. Here we show that the bacterially expressed and purified carboxy-terminal region (CTR) of p105 abolishes the binding of p50 homodimers to a kappa B motif but minimally affects the binding of p65 homodimers and NF-kappa B. By contrast, MAD-3 inhibits the binding of p65 and NF-kappa B but not p50. Both the CTR and MAD-3 interact with their respective targets through physical association both in vitro and in vivo. The CTR can be expressed as an independent entity and thus may play two roles, as a cis inhibitor built into the p105 molecule and as a trans regulator of p50. PMID- 1639071 TI - Ternary complex formation over the c-fos serum response element: p62TCF exhibits dual component specificity with contacts to DNA and an extended structure in the DNA-binding domain of p67SRF. AB - The serum response element (SRE) plays an essential role in the transcriptional regulation of proto-oncogene c-fos. A ternary complex, consisting of transcription factors p67SRF and p62TCF bound to the SRE is present in several cell types and its formation has been correlated with inducibility of the gene in different cells by serum, epidermal growth factor and phorbol esters. Interaction of p62TCF with the SRE in vitro exhibits both a degree of sequence specificity and a strict dependence on the presence of bound p67SRF. A 90 amino acid DNA binding domain of p67SRF (coreSRF) suffices for ternary complex formation. DNase I footprinting and UV-mediated DNA-protein crosslinking experiments presented here show that direct DNA contacts are made by p62TCF with the 5' sequence of the SRE and thus explain the sequence dependence of ternary complex formation. Additionally, analysis of ternary complex formation by chimaeras of coreSRF and the related yeast protein ArgRI as well as comprehensive mutagenesis of non conserved residues between the two proteins has yielded a coreSRF mutant specifically unable to interact with p62TCF and demonstrates that an extended structure in coreSRF is required for this interaction. Thus p62TCF exhibits dual component specificity in ternary complex formation over the c-fos SRE. PMID- 1639073 TI - Sequence-specific interaction of the HMG box proteins TCF-1 and SRY occurs within the minor groove of a Watson-Crick double helix. AB - The high mobility group I (HMG) box is proposed to mediate DNA binding in a novel group of transcription-regulating proteins. Two of these, the proteins encoded by the T cell-specific TCF-1 and the mammalian sex-determining gene SRY, carry a single HMG box with specificity for the heptamer motif A/T A/T C A A A G. We have now analysed the mode of interaction of the HMG boxes of TCF-1 and SRY with this motif. Methylation interference footprinting revealed that both HMG boxes contacted adenines on both strands in the minor groove, whereas no major groove guanine contacts were discerned. Diethylpyrocarbonate (DEPC) carbethoxylation interference footprinting of TCF-1 indicated the absence of major groove contacts on positions 5, 6 and 7 of the motif. Carbethoxylation interference was observed, however, on positions 2, 3 and 4 and to a lesser extent on position 1 in the major groove. Combined T----C and A----I substitution, which changes the surface of the major groove but leaves the minor groove intact, did not interfere with sequence-specific binding by TCF-1 and SRY. These observations indicate that recognition of the heptamer motif by the HMG boxes of the distantly related TCF-1 and SRY proteins predominantly occurs through nucleotide contacts in the minor groove. PMID- 1639072 TI - The DNA target of the trp repressor. AB - Unexpected features seen by high resolution X-ray crystallography at the interface of the trp repressor and the 'traditional' trp operator provoked the claim that the DNA fragment used in the crystal structure is not the true operator, and therefore that the crystal structure of the trp repressor-operator complex does not portray a specific interaction. An alternative sequence was proposed mainly on the basis of mutational studies and gel retardation analysis of short target duplexes (Staacke et al., 1990a,b). We have reexamined the sequence consensus in trpR-repressible promoters and analyzed the mutagenesis experiments of others including Staacke et al. (1990a) and found them fully consistent with the interactions of the traditional operator sequence seen in the crystal structure, and stereochemically inconsistent with the above referenced alternative model. Moreover, an in vitro trp repressor-DNA binding analysis, employing both novel DNA constructs devised to avoid previously encountered artifacts as well as full-length promoter sequences, indicates that the traditional operator used in the crystal structure is the preferred target of the trp repressor. PMID- 1639074 TI - Determination of the structure of the nucleocapsid protein NCp7 from the human immunodeficiency virus type 1 by 1H NMR. AB - The retroviral gag nucleocapsid protein NCp7 (72 amino acids) of HIV-1 (LAV strain), which contains two successive zinc fingers of the Cys-X2-Cys-X4-His-X4 Cys form linked by a stretch of basic residues, promotes viral RNA dimerization and encapsidation and activates annealing of the primer tRNA to the initiation site of reverse transcription. The structure of NCp7 and other shorter fragments was studied by 600 MHz 1H nuclear magnetic resonance (NMR) in aqueous solution to account for its various biological properties. Complete sequence specific 1H NMR assignments of the 13-51 residues of NCp7 encompassing the two zinc fingers was achieved by two-dimensional NMR experiments and the three-dimensional structure of (13-51)NCp7 was deduced from DIANA calculations, using nuclear Overhauser effects as constraints. The structure of the zinc complexed form of NCp7 is characterized by a kink at the Pro31 level in the basic Arg29-Ala-Pro-Arg-Lys-Lys Gly35 RNA binding linker leading to a proximity of the Lys14-Cys18 to the Gly35 Cys39 sequences, which belong to the folded proximal and distal zinc fingers, respectively. Accordingly, the aromatic residues Phe16 and Trp37 were found to be spatially close. The Lys33 and Lys34 side-chains involved in viral RNA dimerization were solvent exposed. The N- and C-terminal sequences of NCp7 behave as flexible independent domains. The proposed structure of NCp7 might be used to rationally design new anti-viral agents aimed at inhibiting its functions. PMID- 1639075 TI - Identification of a portable determinant of cell cycle function within the carboxyl-terminal domain of the yeast CDC34 (UBC3) ubiquitin conjugating (E2) enzyme. AB - The ubiquitin conjugating (E2) enzyme encoded by CDC34 (UBC3) in Saccharomyces cerevisiae is required for the G1 to S transition of the cell cycle. CDC34 consists of a 170 residue amino-terminal domain that is homologous to that found in other E2s, followed by a 125 residue carboxyl-terminal domain that is specific to CDC34. We found that a truncation mutant of CDC34 which lacked the CDC34 carboxyl-terminal domain could not support the essential function of CDC34 in the cell cycle in vivo. To explore further the role of the carboxyl-terminal domain in determining the cell cycle function of CDC34, we constructed and characterized genes encoding chimeric E2s incorporating sequences from CDC34 and the related but functionally distinct E2 RAD6 (UBC2). We found that a construct encoding a chimeric RAD6-CDC34 ubiquitin conjugating enzyme, in which the 21 residue acidic carboxyl-terminal domain of RAD6 has been replaced with the 125 residue carboxyl terminal domain of CDC34, performed the essential functions of CDC34 in vivo. This chimeric E2 also complemented the growth deficiency, UV sensitivity and sporulation deficiency of rad6 mutant strains. Deletion analysis of the CDC34 carboxyl-terminal domain in both CDC34 and the RAD6-CDC34 chimeric E2 identified a region comprising residues 171-244 of CDC34 that was sufficient to confer CDC34 function on the amino-terminal domains of CDC34 and RAD6. We suggest that this region interacts with substrates of CDC34 or with trans-acting factors (such as CDC34-specific ubiquitin protein ligases) that govern the substrate selectivity of CDC34. Congruent results demonstrating a positive role for the carboxyl terminal domain of CDC34 in the essential function of CDC34 have also been obtained by Silver et al. (1992) and are reported in the accompanying paper. PMID- 1639076 TI - A chimeric ubiquitin conjugating enzyme that combines the cell cycle properties of CDC34 (UBC3) and the DNA repair properties of RAD6 (UBC2): implications for the structure, function and evolution of the E2s. AB - The CDC34 (UBC3) protein from Saccharomyces cerevisiae has a 125 residue tail that contains a polyacidic region flanked on either side by sequences of mixed composition. We show that although a catalytic domain is essential for CDC34 activity, a major cell cycle determinant of this enzyme is found within a 74 residue segment of the tail that does not include the polyacidic stretch or downstream sequences. Transposition of the CDC34 tail onto the catalytic domain of a functionally unrelated E2 such as RAD6 (UBC2) results in a chimeric E2 that combines RAD6 and CDC34 activities within the same polypeptide. In addition to the tail, the cell cycle function exhibited by the chimera and CDC34 is probably dependent on a conserved region of the catalytic domain that is shared by both RAD6 and CDC34. Despite this similarity, the CDC34 catalytic domain cannot substitute for the DNA repair and growth functions of the RAD6 catalytic domain, indicating that although these domains are structurally related, sufficient differences exist to maintain their functional individuality. Expression of the CDC34 catalytic domain and tail as separate polypeptides are capable of only partial function; thus, while the tail displays autonomous structural characteristics, there is considerable advantage gained when both domains coexist within the same polypeptide. The ability of these and other derivatives to restore partial function to a cdc34 temperature-sensitive mutant but not to a disruption mutant suggests that interaction between two CDC34 polypeptides is a requirement of CDC34 activity. Based on this idea we propose a model that accounts for the initiating steps leading to multi-ubiquitin chain synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639077 TI - HSD restriction-modification proteins partake in latent anticodon nuclease. AB - Phage T4-induced anticodon nuclease triggers cleavage-ligation of the host tRNA(Lys). The enzyme is encoded in latent form by the optional Escherichia coli locus prr and is activated by the product of the phage stp gene. Anticodon nuclease latency is attributed to the masking of the core function prrC by flanking elements homologous with type I restriction-modification genes (prrA hsdM and prrD-hsdR). Activation of anticodon nuclease in extracts of uninfected prr+ cells required synthetic Stp, ATP and GTP and appeared to depend on endogenous DNA. Stp could be substituted by a small, heat-stable E. coli factor, hinting that anticodon nuclease may be mobilized in cellular situations other than T4 infection. Hsd antibodies recognized the anticodon nuclease holoenzyme but not the prrC-encoded core. Taken together, these data indicate that Hsd proteins partake in the latent ACNase complex where they mask the core factor PrrC. Presumably, this masking interaction is disrupted by Stp in conjunction with Hsd ligands. The Hsd-PrrC interaction may signify coupling and mutual enhancement of two prokaryotic restriction systems operating at the DNA and tRNA levels. PMID- 1639079 TI - Detection of direct-acting mutagens in ambient air: a comparison of two highly sensitive mutagenicity assays. AB - Ambient air has been shown to contain numerous hazardous pollutants, many of which are known or suspected carcinogens and mutagens. Bioassays play a prominent role in the characterization of these genotoxic pollutants, and as new test methods are developed, it is incumbent upon researchers to evaluate assay performance and report relative merits. In this study, two Salmonella test methods (the spiral and preincubation assays) were assessed to determine their usefulness as screening methods for monitoring direct-acting mutagens in ambient air. The spiral assay automates the conventional plate-incorporation assay and has been shown to reduce the labor, materials, and sample mass required to perform mutagenicity testing. The preincubation assay has been shown to enhance test sensitivity for certain classes of compound, thereby reducing the amount of sample required for dose-response analysis. Both assays were used to test organic extracts of airborne particulate matter collected in Tokyo during the winters of 1988 and 1990. In addition to the conventional tester strains TA98 and TA100, two newly developed YG strains were evaluated. Strains YG1024 and YG1029-derived from TA98 and TA100, respectively-contain an acetyltransferase plasmid that confers upon the strains greater sensitivity towards nitroarenes. Results from this study indicated that both assays were able to detect direct-acting mutagens in the Tokyo air samples. The mutagenic activity associated with the samples was directly related to the particle mass present in a given volume of air. Mutagenic response was greater in the spiral assay relative to the preincubation assay, especially when YG tester strains were used. The YG strains were significantly more sensitive to mutation than the TA strains in both assays, which suggests that nitroaromatics are an important class of genotoxic contaminant present in Tokyo air. PMID- 1639078 TI - Molecular analysis of mutations induced by the intercalating agent ellipticine at the hisD3052 allele of Salmonella typhimurium TA98. AB - We have used DNA colony hybridization, the polymerase chain reaction (PCR), and direct DNA sequencing to determine the mutations induced by the intercalating agent ellipticine in Salmonella typhimurium TA98 in the presence of S9. Of 400 ellipticine-induced revertants that were selected at a mutant yield that was ninefold over the background, 85.5% contained a GC or CG deletion within a common CGCGCGCG hotspot; this deletion occurred among 47% of the spontaneous revertants. In addition to this hotspot, the ellipticine spectrum contained two deletion warmspots that reside opposite each other in looped-out regions of a possible DNA secondary structure. Ellipticine and its metabolites likely revert Salmonella strain TA98 by forming DNA adducts that promote slippage-mismatches and by stabilizing these slipped mismatched sequences via intercalation. The involvement of these mechanisms, along with a likely role for DNA secondary structures and a possible role for DNA gyrase, may account for the site specificity exhibited by ellipticine in strain TA98. PMID- 1639080 TI - Genetic and environmental influences on baseline SCE. AB - Previous population-based studies have identified subject characteristics that, when combined, can account for approximately 20% of the observed interindividual variation in baseline SCE rates. In the present investigation, a classic twin study design was used to address the issue of the relevance of genetic factors to baseline SCE rates and to identify other demographic, hematologic, and exposure variables predictive of SCE rate. Questionnaire data and peripheral blood samples from 136 monozygotic and 88 dizygotic twins (age range: 25-81 years) were obtained. Among the large number of variables examined, univariate analyses (including ANOVA tests for the categorical variables and Pearson-product moment correlations for the quantitative variables) revealed smoking status, coffee drinking status, sex, white blood cell count, and absolute numbers of lymphocytes and neutrophils to have significant effects on SCE rates. A stepwise multiple regression analysis showed that together, smoking and coffee drinking status entered at the first step accounted for 21% of the observed variance in SCE, with a further 6% being contributed by the demographic and hematologic variables added in subsequent steps. Finally, the twin analyses showed that after adjustment of the data set for smoking and other significant predictors, genetic factors accounted for approximately 30% of the variation in SCE rates. Thus these data support the hypothesis of a significant genetic influence on baseline SCE. PMID- 1639081 TI - Mitogenesis, micronuclei, and carcinogenesis in the rat liver: some basic inconsistencies. AB - The rodent liver carcinogen, mitogen, and peroxisome proliferator, methylclofenapate (MCP), has been investigated as a chemical mitogen for use in the rat liver micronucleus assay. A series of experiments comparing MCP with the potent mitogen 4-acetylaminofluorene (4AAF) and with 2/3 partial hepatectomy showed unexpected differences between the three treatment regimes as monitored by the expression of micronucleated hepatocytes (MH) in livers initiated with N nitrosodimethylamine (NDMA). These differences were observed in both the profile of MH induction, as a function of time after mitogenic stimulation, and in the magnitude of response. There was no correlation between the magnitude of MH induction and the degree of mitogenesis triggering the MH induction. It is concluded that the yield of MH observed in a rat liver micronucleus assay is not a simple function of the level of DNA damage induced by the initiating agent (here NDMA). This indicates the need for caution in the interpretation of data obtained in the liver micronucleus assay for chemicals of unknown carcinogenicity. The use of acridine orange as a fluorescent stain for use with isolated hepatocytes is described. PMID- 1639082 TI - Mitogenic activity of quinoline to the rat, mouse, and guinea pig liver: empirical correlations with hepatic carcinogenicity. AB - Previous studies have shown that the rat liver carcinogen quinoline is essentially nongenotoxic to the rat liver in vivo. Those studies also established it as a potent mitogen to rat liver. The present experiments have established quinoline as a mitogen to the mouse liver, a tissue in which it is also reported to be carcinogenic. In contrast, quinoline is reported to be noncarcinogenic to the guinea pig liver, and the present data establish it to be essentially nonmitogenic to the guinea pig liver. It is concluded that the mitogenicity of quinoline correlates better with its hepatocarcinogenic properties than does its genotoxicity in vivo. PMID- 1639083 TI - Evidence that inhibitor(s) are formed which may interfere with the growth of revertant colonies in the Ames Salmonella and the E. coli tryptophan reverse mutation assays when strictly anaerobic conditions are used. AB - Spontaneous and chemically induced revertant colonies were not observed on plates when a strictly anaerobic environment and anaerobically prepared media were used to perform the Ames histidine reversion assay with each of eight different Salmonella strains. A similar effect was observed when the E. coli tryptophan reverse mutation assay was performed under strictly anaerobic conditions. We provide evidence here that under anaerobic conditions growth inhibitor(s) are formed by the S. typhimurium and E. coli bacteria when the limited histidine and tryptophan, respectively, are depleted from the medium. The inhibitor(s) are nonspecific and inhibit the growth not only of prototrophic bacteria but also of the inhibitor-producing bacteria as measured by neutralized supernatants of growth-limiting minimal liquid cultures. Inhibitor(s) are also formed in stationary phase cultures of Salmonella and E. coli in minimal liquid medium supplemented with excess histidine and tryptophan, respectively. These results suggest that inhibitor formation under anaerobic conditions is a physiological phenomenon which interferes with at least two reverse mutation assays. Whether or not it also interferes with the reverse mutagenesis process remains to be determined. PMID- 1639084 TI - Adaptive response of Vibrio cholerae and Escherichia coli to nitrofurantoin. AB - Pretreatment with sublethal doses of nitrofurantoin induced adaptive response in both Vibrio cholerae and Escherichia coli cells as indicated by their greater resistance to the subsequent challenging doses of the same drug. Adaptive response was maximum corresponding to pretreatment drug concentrations of 0.40 microgram/ml and 0.015 microgram/ml respectively for V. cholerae OGAWA 154 (wild type) and E. coli K-12 AB 2463 (recA-) cells. Adaptive response was inhibited by chloramphenicol (100 micrograms/ml) indicating the need of concomitant protein synthesis. Induction of adaptive response in recA deficient E. coli cells indicated that it was different from the conventional "SOS" response. Melting temperature of DNA of V. cholerae cells subjected to adaptive (0.4 microgram/ml for 1 hr) and challenging (120 micrograms/ml for 1 hr) doses of nitrofurantoin (76 degrees C) was closer to that of native DNA (75 degrees C) vis-a-vis DNA isolated from nonadapted and drug treated cells (77.5 degrees C). Also, DNA isolated from V. cholerae cells subjected to adaptive and challenging doses of the drug revealed the presence of fewer interstrand cross-links (16% reversible DNA) vis-a-vis DNA from nonadapted but drug treated cells (55% reversible DNA). Photomicrographic studies revealed that V. cholerae cells that were nonadapted but drug treated grew into long filamentous forms (4.25 +/- 2.97 micron) whereas those subjected to both adaptive and challenge doses of the drug exhibited much less filamentation (2.08 +/- 0.84 micron) vis-a-vis native cells (1.42 +/- 0.5 micron). Similar results on DNA melting temperature, cross-links in DNA, and filamentation of cells were obtained for E. coli AB 2463 (recA-) cells subjected to adaptive and challenging treatments with nitrofurantoin. Almost equal degree of resistance against nitrofurantoin could be induced in both V. cholerae OGAWA 154 (wild type) and E. coli strain PJ3 (AB 1157 ada-) when these cells were pretreated with nontoxic doses of hydrogen peroxide or nitrofurantoin. Evidence obtained in this work on the nature of the nitrofuratoin induced adaptive response with particular references to the oxidative and/or alkylating DNA damages were discussed. Nitrofuratoin induced adaptive response appeared similar to that elicited by furazolidone in V. cholerae cells and appeared to be directed towards oxidative and not alkylating adaptive repair pathway. PMID- 1639085 TI - Decemtione (Imidan)-induced single-strand breaks to human DNA, mutations at the hgprt locus of V79 cells, and morphological transformations of embryo cells. AB - To study the genotoxic activity of Decemtione (Imidan), this substance was subjected to a series of tests. After preliminary cytotoxicity testing, the capacity of Decemtione to damage human DNA was determined by alkaline elution of DNA and DNA unwinding. Both tests gave positive results, suggesting that Decemtione was able to induce single-strand breaks in DNA. This capacity was higher in the absence and lower in the presence of the S9 fraction. The potential mutagenicity of Decemtione was followed on the basis of its ability to induce resistance to 6-thioguanine in V79 hamster cells. Unlike the induction of single strand breaks, Decemtione showed, in the absence of the metabolic activation system, a very weak mutagenic effect, which was, however, significantly higher in the presence of the S9 fraction. The ability of the substance to transform diploid cells under in vitro conditions was followed on the basis of morphological transformation of Syrian hamster embryo cells. The results showed that Decemtione, like positive carcinogenes, induced a significant elevation in morphologically transformed colonies of embryo cells. The results suggest a carcinogenic potential of this organophosphate insecticide. PMID- 1639086 TI - Intermixing of resident Golgi membrane proteins in rat-hamster polykaryons appears to depend on organelle coalescence. AB - We have used the synchronized formation of a mixed cytoplasm upon heterokaryon formation as a model for investigating the cisternal-specific transport of resident proteins between neighboring Golgi apparatus. Rat NRK and hamster 15B cells were fused by UV-inactivated Sindbis virus and then incubated for various time periods in the presence of cycloheximide. The resident Golgi apparatus proteins, rat GIMPc and Golgp 125, were localized with species-specific monoclonal antibodies. Immunofluorescent colocalization of rat and hamster Golgi membrane proteins was observed with a t1/2 of 1.75 h at 37 degrees C. Colocalization of resident, but not transient, Golgi membrane protein was concomitant with formation of a large extended Golgi complex and was accompanied by the acquisition of endoglycosidase H resistance by preexisting Golgp 125. Dispersal of the extended Golgi complex by nocodazole revealed that colocalization of resident Golgi proteins was due to intermixing of proteins in the same Golgi element rather than overlapping of closely apposed Golgi structures. Incubation of the polykaryons at 20 degrees C inhibited both the colocalization of GIMPc and Golgp 125 and the formation of an extended Golgi complex. Little change in the number of cisternae/stack in cross sections of the Golgi apparatus was observed upon cell fusion, and in the extended Golgi complex the hamster resident protein remained localized to one side of the Golgi stack. Surprisingly, the morphological identity of the rat and hamster Golgi units appeared to be maintained in the heterokaryons. These results suggest that the intermixing of resident Golgi membrane proteins requires direct physical continuity between Golgi elements and that resident Golgi membrane proteins are preferentially excluded from the non-clathrin-coated transport vesicles budding from Golgi cisternae. PMID- 1639087 TI - Modulation of proteoglycan metabolism by human fibroblasts maintained in an endogenous three-dimensional matrix. AB - This report describes synthesis and degradation of proteoglycans by human gingival fibroblasts growing in an endogenous three-dimensional matrix. Cells grown in the matrix cultures demonstrated a high rate of proteoglycan synthesis, varying between 2 and 4 times that of cells maintained in monolayer cultures. In addition, the relative amount deposited into the cell layer was increased in the matrix cultures, constituting 70% to 90% of the synthesized material during the first 24 h. Comparable levels for the monolayer cultures were 30% to 60%. The majority of the 35S-sulfate-labeled material in both matrix (80%) and monolayer (62%) cultures was susceptible to chondroitin ABC-lyase digestion. The major product was a low Mr (120,000) proteoglycan which could be immunoprecipitated by an antibody against PGII (decorin). In addition, the cells synthesized two chondroitin ABC-lyase-sensitive proteoglycans, one with Mr greater than 400,000, one with an apparent Mr of 250,000, as well as two heparan sulfate proteoglycans with Mr greater than 250,000. The low Mr dermatan sulfate, decorin, was also the major component deposited in the three-dimensional matrix, constituting about 60% of the total sulfate incorporation. In contrast, fibroblasts in monolayer cultures deposited only a small amount (13%) of decorin (PGII) in the cell layer, and the major proteoglycan in this compartment was heparin sulfate. The rate of release of the newly deposited proteoglycans was the same in the two culture conditions, although material released from the three-dimensional matrix cultures contained small Mr components indicating a higher degree of degradation. These studies show differences in proteoglycan metabolism by gingival fibroblasts grown in an endogenous matrix and in monolayer cultures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639088 TI - N-linked glycoproteins associated with flagellar scales in a flagellate green alga: characterization of interactions. AB - Glycoproteins associated with one type of flagellar scale (p-scale) isolated from the flagellate green alga Tetraselmis striata (Prasinophyceae) were shown to bind the mannose-specific lectin GNA (Galanthus nivalis agglutinin). Enzymatic deglycosylation of the glycoproteins with N-glycosidase F led to an electrophoretic mobility shift to lower molecular masses in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and abolished GNA-binding strongly indicating that most of the scale-associated glycoproteins contain asparagine-linked oligosaccharide side chains presumably of the high mannose type. To evaluate the significance of N-linked glycoproteins for scale structure and integrity, p-scales were digested with various proteases or extracted with 8 M urea and their ultrastructure and protein composition determined. The results show that while scale-associated N-linked glycoproteins do not determine the overall structure of the scale subunits (which consist of complex polysaccharides), they are apparently involved in mediating linkages between scale subunits; we have tentatively identified one glycoprotein of Mr 280,000 which may link outer scale subunits to one another. In addition, some scale associated N-linked glycoproteins may provide connections between the layer of p scales and the underlying flagellar membrane. PMID- 1639089 TI - Construction of an apparatus for perfusion cell cultures which enables in vitro experiments under organotypic conditions. AB - The value of cultured cells in cell biological, pharmaceutical or biotechnological research depends on the degree of terminal cell differentiation. In conventional Petri dishes or tissue culture plates it is often difficult to achieve culture conditions which resemble the in situ situation of intact tissue, as regards optimal cell adhesion, exchange of nutrients and metabolic products. These limitations prompted us to develop simple laboratory tools which optimize the environment of cultured cells. A perfusion apparatus with various culture containers and compatible cell holder sets was constructed which allows the simulation of organotypic conditions. (i) The cells can be kept on individual and interchangeable support materials for an optimal cell attachment. (ii) Culture medium can be perfused during the whole culture period. (iii) One type of the new culture container can be perfused with different media at the apical and basal side of the cells, thus mimicking the organotypic environment that applies for epithelial monolayers. Cell culture experiments with renal collecting duct epithelia exhibited an excellent morphological appearance showing typical features of principal and intercalated cells. PMID- 1639090 TI - Milk lipid globule precursor release from endoplasmic reticulum reconstituted in a cell-free system. AB - Lipid droplet precursors of milk lipid globules are believed to be derived from elements of endoplasmic reticulum in milk-secreting mammary epithelial cells. Endoplasmic reticulum isolated from mammary gland was able to generate small droplets morphologically resembling microlipid droplet precursors of milk lipid globules. Droplet generation was time and temperature dependent and required a cytosol fraction of Mr greater than 10,000. Droplet generation was enhanced by, but did not require, addition of nucleoside triphosphates, fatty acids, coenzyme A, glycerol-3-phosphate, and dithiothreitol. Microlipid droplets generated in this cell-free system were enriched in triacylglycerols and resembled microlipid droplets formed within mammary epithelial cells in polar lipid and polypeptide composition. Endoplasmic reticulum immobilized onto nitrocellulose retained activity in generation of putative microlipid droplets, and this immobilization method provided a facile means for separation of the donor from the generated products. PMID- 1639091 TI - Immunolocalization of a specific type of prosome close to the bile canaliculi in fetal and adult rat liver. AB - Prosomes are mRNA-associated RNP particles and cofactors of untranslated (ribosome-) free mRNP having a multicatalytic proteinase (MCP; proteasome) activity. The expression of prosomal proteins in fetal development of the rat liver was investigated by indirect immunofluorescence, using a panel of monoclonal antibodies to individual prosomal proteins (p-mAbs). In all fetal and adult stages tested, strong immunofluorescence staining was observed with the p31K-specific p-mAb exclusively, whilst Western blot analysis showed reactivity also with the p27K and p33K antigens. Double labeling with the 31K p-mAb and an anti-cytokeratin antibody showed that the prosome antigen superimposes partially onto this type of intermediate filaments (IF), confirming earlier observations made on cultured cell lines of various types. Most interestingly, the p31K antigen was found preferentially in the pericanalicular zone of hepatocytes in the developing liver, from day 17 onwards up to the adult state. This shows a preferential concentration of prosomes of a specific type, including the p31K antigen, in the morphologically and possibly functionally specialized apical domain of the hepatocyte, in a differentiation-related fashion. PMID- 1639092 TI - Identification of two distinct microtubule binding domains on recombinant rat MAP 1B. AB - A set of partially overlapping cDNA clones covering 9 kb of continuous sequence encoding the high molecular weight microtubule-associated protein (MAP) 1B, was isolated from a rat brain library in lambda gt11. The protein encoded was immunoreactive with monoclonal antibodies raised against calf MAP 1B, rat MAP 1X, and rat MAP 5, as shown by immunoblotting. Using Northern blot analysis, it was shown that the level of MAP 1B mRNA increased dramatically upon nerve growth factor-induced PC12 cell differentiation. The expression of polypeptides encoded by cDNA constructs, in conjunction with microtubule binding assays, revealed two separate microtubule binding domains, corresponding to sequences at the 5' and 3' end of the mRNA. As shown by DNA sequencing, the binding domain encoded by 5' terminal sequences consisted of the basic repeat motif KKEE(I/V), previously identified in mouse MAP 1B (Noble, M., S. A. Lewis, N. J. Cowan, J. Cell Biol. 109, 3367-3376 (1989)). The second binding domain, too, was found to be basic, but without any apparent repeat structure. It is concluded that single proteolytically unprocessed MAP 1B molecules would have the potential to function as microtubule cross-linkers. PMID- 1639093 TI - Role of cytoskeleton in cell shaping of developing mesophyll of wheat (Triticum aestivum L.). AB - The effects of oryzalin and cytochalasin B (CB) on microtubule and actin microfilament arrays and on cell shaping were investigated in developing wheat mesophyll. Excised immature leaf sections capable of differentiating were incubated with the drugs. The behavior of the cytoskeleton was monitored by fluorescence microscopy after labeling with fluorescent dyes. Brief incubation with oryzalin (40 min, 10 microM) caused disassembly of microtubules. Recovery of microtubule arrays was comparatively slow after removal of the drug. Cells failed to establish transverse cortical bands of microtubules and transverse hoops of wall reinforcement. They expanded isodiametrically rather than longitudinally without forming lobes typical of wheat mesophyll cells. Brief treatment with CB (60 min, 20 micrograms ml-1) appeared to disrupt the microfilament arrays. Filaments recovered rapidly after removal of CB, and cells were able to shape in an apparently normal fashion. Continuous incubation at comparatively low concentration of CB (4 micrograms ml-1) appeared to cause selective loss of the fine transverse cortical microfilament arrays. Cortical transverse microtubule arrays persisted, but failed to form distinct bands in the majority of the cells. Cells were able to elongate in an almost normal fashion, but no lobes were formed. PMID- 1639094 TI - Lung surfactant protein A (SP-A) enhances serum-independent phagocytosis of bacteria by alveolar macrophages. AB - Surfactant protein A (SP-A) is the main protein component of lung surfactant. We studied the involvement of SP-A in body defense, i.e., effect of SP-A on the phagocytosis of bacteria by alveolar macrophages. We show here that SP-A enhances the phagocytosis of some non-opsonized bacteria: Escherichia coli growing logarithmically (E. coli/log), Pseudomonas aeruginosa/log as well as from stationary phase (P. aeruginosa/stat) and Staphylococcus aureus/log. Furthermore, not only serum-independent phagocytosis was effected by SP-A but also phagocytosis of serum-opsonized S. aureus/stat. No effect of SP-A on phagocytosis was observed with E. coli/stat neither on serum-independent nor on serum dependent phagocytosis and on phagocytosis of non-opsonized S. aureus/stat. Thus, effect of SP-A on phagocytosis is dependent on bacterial species and on the growth phase of the microorganisms, and this effect is concentration dependent. We studied two different human recombinant SP-As and SP-A isolated from lung lavage material from proteinosis patients. These SP-A molecules contain different isomeric chains, and they differ in complexity of their structure. Qualitatively, we found the same effect with all three substances. Quantitatively, the proteinosis SP-A that forms the most complex structure was the most effective. Taken together, we demonstrated a stimulating effect of SP-A on serum-independent as well as on serum-dependent phagocytosis of bacteria by alveolar macrophages, both depending on species and growth phase of the bacteria. PMID- 1639095 TI - Long-term comprehensive care of cardiac patients. Recommendations by the Working Group on Rehabilitation of the European Society of Cardiology. PMID- 1639096 TI - Ischemic heart disease: risk stratification and intervention. Risk of poor quality of life. PMID- 1639097 TI - Cardiac surgery. PMID- 1639098 TI - Chronic heart failure. PMID- 1639099 TI - Regulation of graft-versus-host-reaction by Mlsa-reactive donor T cells. AB - Injection of A/J splenocytes (H-2Dd, Mlsc) into unirradiated (A/J x CBA)F1 (BAF1) host mice (H-2Dd/k, Mlsd) results in an acute suppressive graft-vs.-host reaction (GVHR), characterized by immune dysfunction and appreciable donor cell engraftment; injection of the CBA/J parent (H-2Dk, Mlsd), which recognizes no Mls disparity in the host, results in little or no GVHR. Furthermore, the Mlsa reactive V beta 6 and V beta 8.1 T cell subsets in A/J T cells expand significantly in the GVHR host. Finally, depletion of V beta 6+ and V beta 8.1+ from the A/J population abrogates the proliferative response to BAF1 in vitro and the development of GVHR in vivo. Thus, the response to Mls determinants can contribute to the generation of a GVHR. PMID- 1639100 TI - Evidence that mannose recognition by splenic sinusoidal cells plays a role in the splenic entry of lymphocytes. AB - Previous studies demonstrated that mannan is a potent inhibitor of splenic entry of lymphocytes and mediates its inhibitory effect at an unidentified site in the spleen rather than acting directly on lymphocytes. This report describes the in vivo site of action of mannan. In vivo localization studies with fluoresceinated preparations of mannan (Fl-mannan) and a mannose-6-phosphate-containing yeast phosphomannan monoester core from P. holstii exopolysaccharide (Fl-PPME) demonstrated that the polysaccharide specifically localize in the splenic marginal sinuses in cells with a dendritic morphology termed splenic sinusoidal cells (SSC). Uptake of the polysaccharides by SSC was mediated by a mannan specific receptor which was saturable and of high avidity. Several lines of evidence suggested that mannan uptake by SSC inhibited splenic entry of lymphocytes. First, the ability of SSC to bind Fl-mannan and Fl-PPME closely paralleled the ability of these polysaccharides to inhibit splenic entry of lymphocytes. In fact, doses of mannan and PPME which would saturate SSC mannan receptors completely blocked splenic entry of lymphocytes. Second, SSC are situated at the initial entry point of lymphocytes into spleen and passage of lymphocytes through the SSC region of spleen was profoundly inhibited by mannan. Finally, direct evidence for adhesion between lymphocytes and SSC was obtained with spleen cell suspensions where clustering between Fl-mannan labeled SSC and lymphocytes was observed. Collectively, these data indicate that mannan (and PPME) inhibit splenic entry of lymphocytes by interacting with SSC, cell which play a critical role in the entry of lymphocytes into the spleen. Whether mannan specific receptors on SSC directly mediate lymphocyte-SSC adhesion or play on indirect role in modifying lymphocyte migration requires further investigation. PMID- 1639101 TI - Anti-human interleukin-6 receptor antibody inhibits human myeloma growth in vivo. AB - Myeloma is one of the interleukin (IL)-6-related diseases to which abnormal expression of IL-6 has been reported to be linked. We examined the in vivo inhibitory effect of anti-human IL-6 receptor (IL-6R) antibody on human myeloma cell growth in mice. SCID mice were subcutaneously inoculated with solid tumor of the myeloma cell line S6B45 in which human IL-6 was acting as an autocrine growth factor. Ten intraperitoneal administrations of 100 micrograms of the anti-human IL-6R antibody PM1 at 48-h intervals strongly inhibited the growth of S6B45 cells when the administration started 24 h after tumor inoculation. The tumor growth inhibition in vivo was also observed by administration of the anti-human IL-6 antibody MH166 using the same procedure as for PM1. The inhibitory effect of PM1 was not significant when the administration started 5 or more days after tumor inoculation. This work indicates that anti-human IL-6R antibody, as well as anti human IL-6 antibody inhibits human myeloma growth in vivo, and provides an animal model for testing the therapeutic value of agents such as antibodies to human IL 6, IL-6R and gp130, an IL-6R-associated signal transducer, in the treatment of human myelomas. PMID- 1639102 TI - Glycosidase inhibitors (castanospermine and swainsonine) and neuraminidase inhibit pokeweed mitogen-induced B cell maturation. AB - Castanospermine (CSP), an inhibitor of alpha-glucosidase, enhanced immunoglobulin (Ig) release in a Staphylococcus aureus Cowan I (SAC)-induced lymphocyte culture (Scand. J. Immunol. 1990. 32: 529). In a pokeweed mitogen (PWM)-human lymphocyte culture, unlike the SAC-stimulated system, CSP strongly decreased the number of IgG-, IgA- and IgM-secreting cells as well as that of Ig-bearing cells. Peripheral blood lymphocytes treated with swainsonine, a mannosidase II inhibitor, or with neuraminidase also showed a reduced response to PWM. In cross culture experiments, only a mixture of B cells pretreated with either agent and untreated T cells showed such a suppressive effect. Adhesion was decreased between B cells treated with either agent and untreated T cells, but not between treated T cells and untreated B cells. These results demonstrate that a certain alteration in B cell membrane oligosaccharides inhibited the T cell-B cell adhesion in the PWM culture, leading to an arrest of B cell maturation. Considering that these inhibitors eventually prevent terminal sialic acid addition, the present study provides evidence that sialic acids on B cell surface oligosaccharides play a biological role in the T cell-B cell interaction. PMID- 1639103 TI - Phenotypic characterization of KU812, a cell line identified as an immature human basophilic leukocyte. AB - The knowledge about the differentiation of basophilic leukocytes is fragmentary. This report discusses a detailed phenotypic characterization of molecular markers for hematopoietic differentiation in a basophilic leukemia cell line, KU812. The expression of markers for lymphoid, erythroid, neutrophil, eosinophil, monocytic, megakaryocytic, mast cell and basophil differentiation was analyzed at the mRNA level by Northern blots in the KU812 cells, and for reference, in a panel of human cell lines representative of the different hematopoietic differentiation lineages. KU812 was found to express a number of mast cell and basophil-related proteins, i.e. mast cell tryptase, mast cell carboxypeptidase A, high-affinity immunoglobulin (IgE) receptor alpha and gamma chains and the core protein for heparin and chondroitin sulphate synthesis. We found no expression of a number of monocyte/-macrophage or neutrophil leukocyte markers except for lysozyme. From earlier studies, it has been shown that lysozyme is not expressed in murine mucosal mast cell lines. This finding, together with the expression of the mast cell carboxypeptidase in KU812 might distinguish the phenotype of this cell line from that typical of mucosal mast cell lines in rodents. We found a low level of expression of the eosinophil and basophil marker, major basic protein, which might indicate a relationship between basophils and eosinophils. No expression is, however, detected with the eosinophil-specific markers eosinophil cationic protein, eosinophil-derived neurotoxin or eosinophil peroxidase. We also report an extensive screening for inducers of basophilic differentiation of the KU812 cells. The most efficient protocol of induction included serum starvation which led to a dramatic increase in a number of markers specific for mast cells and basophils such as tryptase, carboxypeptidase A and the heparin core protein. Finally, diisopropylfluorophosphate analysis of total protein extracts from KU812 show four labeled protein bands with sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that this cell line expresses at least three previously undescribed serine proteases of which one or more could be a potential basophil-specific marker(s). PMID- 1639104 TI - Strong serum inhibition of specific IgE correlated to competing IgG4, revealed by a new methodology in subjects from a S. mansoni endemic area. AB - A method allowing the immunopurification of human IgE from small volumes of sera with a yield close to 100% (mean = 97.8%; SEM = 0.7) has been developed. The immunopurification eluates were cleared of other class antibodies that could compete with IgE in specific assays. Immunopurification of IgE followed by specific IgE enzyme-linked immunosorbent assay (ELISA) (IMMEL) was then applied to sera of 160 individuals from an area endemic for Schistosoma mansoni. In comparison with radioimmunosorbent test (RAST) and ELISA performed on unfractionated sera, IMMEL provided the highest specific IgE signals. Furthermore, the best correlations between the specific IgE levels and either the specific basophil histamine release levels (r = 0.84; p less than 10(-4) or the anti-S. mansoni skin test values (r = 0.45; p = 10(-4)) were obtained with IMMEL. Measurement of anti-S. mansoni IgE levels in immunopurified fractions and in unfractionated sera of these 160 individuals revealed a strong serum inhibition (geometric means of 98.6% and 96.8% for the adult worms and the larvae, respectively) of the specific IgE reactivity in ELISA. This inhibition was correlated with the anti-adult worm and anti-larval IgG4 levels (r = 0.65; p less than 10(-4) and r = 0.58; p less than 10(-4), respectively). In contrast, this inhibition did not correlate with the specific IgG1, IgG2, IgG3 and IgM levels. Furthermore, the level of specific IgG4 was clearly lower than that of specific IgG1, suggesting that the major contribution of IgG4 in the competition effect is not due to higher levels but rather to a specificity spectrum close to that of the specific IgE. These results support the idea that a specific function of IgG4 in serum might be to control antigen recognition by IgE and consequently, to regulate anaphylactic reactions and IgE-mediated immunity. PMID- 1639105 TI - Structural requirements for the peptide-induced conformational change of free major histocompatibility complex class I heavy chains. AB - In an attempt to define the structural features of peptides which are important for inducing the folding of free class I heavy chains in the absence of beta 2 microglobulin, and to determine whether they are the same as those required to form stable major histocompatibility complex (MHC): peptide adducts, we have used a panel of peptides related to the Db-binding nonamer ASNENMDAM (influenza nucleoprotein residues 366-374) with altered primary structures, and a number of other peptides which have the Db-binding "motif". In this way, we have shown that in addition to the "anchor" residues which define this motif, the alpha amino and carboxyl groups at the N and C termini also play a major role in both inducing the conformational change in free heavy chain (HC) and formation of a stable Db:peptide complex. We also show that the importance of the key residues is affected by the primary sequence "context" in which they appear. In addition, we have extended our original finding that naturally processed epitopes induce a conformational change in free HC to the H2Kb HC, and show that the effect does not require the presence of the class I alpha 3 domain. PMID- 1639106 TI - A survey of protein-DNA interaction sites within the murine immunoglobulin heavy chain locus reveals a particularly complex pattern around the DQ52 element. AB - The expression of immunoglobulin (Ig) genes is regulated at two levels: rearrangement of individual gene segments and transcription of continuous genes. To find transacting factors involved in mediating locus- and segment specific gene activation and expression, we surveyed a 3600-bp genomic region of the murine Ig heavy chain locus, spanning from the DQ52 element to the Ig heavy chain intron enhancer. We discovered nine, previously undescribed, protein-DNA complexes and estimated their individual binding-affinity preferences (Kr) by quantitative gel shift measurements. We observed one novel protein DNA interaction at the enhancer, two in the JH1 region and six within a 300-bp region immediately 5' to the DQ52 locus. The latter show a complex and specific binding pattern when comparing nuclear extracts derived from pre-B cells and fibroblasts. Further characterization of the interactions at the DQ52 locus by electron microscopy revealed the preferential formation of a protein complex binding to the DQ52 locus with pre B cell extracts. This behavior and the clustering of interaction sites 5' to the DQ52 element suggest that this region is involved in the regulation of heavy chain gene assembly. PMID- 1639107 TI - Naturally occurring ABO antibodies: long-term stable, individually distinct anti A IgG spectrotypes. AB - Spectrotypes of naturally occurring IgG antibodies to histo-blood group substance A were analyzed by isoelectric focusing and a newly developed, non-radioactive affinity immunoblotting assay. Specificity was tested by preabsorption of sera on red blood cells and on four different types of blood group substance A. Clonotype banding patterns of sera from 18 different blood donors were individually distinct, most of them showing an oligoclonal pattern with less than 15 visible bands. To analyze the influence of IgG subclass composition on spectrotype patterns, IgG subclasses were measured by ABO enzyme-linked immunosorbent assay (ELISA) and were shown to be mostly IgG1 and IgG2. Anti-A IgG1 spectrotypes could be detected with four sera and were also individually distinct. A series of six and seven serum samples, respectively from two donors was used to analyze the time-related changes of anti-A IgG spectrotypes. Banding pattern of both individuals remained stable during the whole observation period of 167 and 82 days, respectively, and no differences between follow-up samples could be detected. This long-term stability of individual anti-A IgG spectrotypes is backed by constant serum levels of anti-A IgG and -IgM antibodies during the observation period as measured by ABO ELISA. PMID- 1639108 TI - Nitric oxide mediates intestinal pathology in graft-vs.-host disease. AB - We have investigated the involvement of nitric oxide (NO) in intestinal graft-vs. host reaction (GvHR) in mice. Treatment of mice with L-NG-monomethyl arginine (L NMMA), a specific inhibitor of NO synthesis, abolished the mucosal pathology of intestinal GvHR and reduced the associated lymphocytic infiltration of the epithelium. L-NMMA had no effect on splenomegaly in GvHR, nor did it interfere with the growth of an undifferentiated crypt stem cell line, or the production of tumor necrosis factor-alpha by activated macrophages in vitro. In contrast, L NMMA inhibited the enhanced activity of natural killer (NK) cells which occurs in GvHR. We conclude that a NO-dependent mechanism is essential for intestinal immunopathology in GvHR and that this may reflect a role for NO in NK cell function. PMID- 1639109 TI - Correlation between killing activity towards the murine L929 cell line and expression of membrane-associated lymphotoxin-related molecule of human lymphokine-activated killer cells. AB - Human lymphokine-activated killer (LAK) cells expressed a membrane-associated lymphotoxin-related molecule (mLT) which was detected by flow cytometric analysis with anti-lymphotoxin antibody. Upon removal of exogenous interleukin-2 from LAK cell culture medium and another 24 h cultivation, the expression of mLT was decreased. Corresponding to the decrease of mLT expression, the killing activity of LAK cells towards L929 cells was remarkably reduced and killing of MIA PaCa-2 and U937 cells was moderately reduced, whereas killing of Daudi and K562 cells was fully restored. The supernatant of mLT-expressing LAK cells had no cytotoxic activity towards L929 cells in the absence of actinomycin D. Moreover, not only the killing of L929 cells but also that of human tumor cell lines (MIA PaCa-2, U937) by mLT-expressing LAK cells was partially inhibited in the presence of anti lymphotoxin antibody. These results suggest an involvement of mLT in the killing of some tumor target cells by LAK cells. PMID- 1639110 TI - The specificity and efficiency of endogenous peptides in the induction of HLA class I alpha chain refolding. AB - The specificity and efficiency of endogenous peptides in the HLA class I binding have been investigated by the use of a simple procedure that is based on the serological detection of the folding of HLA class I alpha chains that is induced by the binding to specific peptides in the presence of beta 2 microglobulin. HLA class I proteins were solubilized with a nonionic detergent from cultured HLA homozygous B lymphoblastoid cells and dissociated by alkaline denaturation. The resulting unfolded alpha chains were isolated by gel filtration at a neutral pH. The unfolded alpha chains showed a high refolding capacity and specificity when tested in the presence of an excess beta 2 microglobulin against endogenous peptides extracted by alkaline or acid treatment from cultured B lymphoblastoid cells of various HLA class I phenotypes. Cells of identical or overlapping HLA phenotypes clearly showed shared peptides, whereas such peptide sharing was rarely, if at all, seen between cells of non-overlapping HLA phenotypes. The efficiency of endogenous peptides in the induction of refolding was high; at an estimated concentration of 0.2 microM or less, a strong refolding effect was observed. PMID- 1639111 TI - Agonist-induced changes in [Ca2+]i in N1E-115 cells: differential effects of bradykinin and carbachol. AB - The addition of bradykinin to populations of fura-2 loaded N1E-115 neuroblastoma cells produced an increase in intracellular calcium which rapidly reached a peak and returned to baseline within 60 s. The response was concentration dependent and unaffected by removal of extracellular calcium or addition of the inorganic channel blocker Ni2+. Similar transient responses were seen with histamine and angiotensin II and experiments monitoring manganese entry suggest that agonist responses in this cell line involve mainly release of calcium from intracellular stores. However, unlike bradykinin, the response to carbachol, at all concentrations, failed to return completely to baseline suggesting a small secondary influx component and highlighting possible differences between the mechanisms of calcium elevation by these two agonists. PMID- 1639112 TI - The AT2 subtype of the angiotensin II receptors has differential sensitivity to dithiothreitol in specific brain nuclei of young rats. AB - We studied the effect of the sulfhydryl reducing agent dithiothreitol on the binding of the angiotensin II agonist [125I][Sar1]-angiotensin II to AT2 receptors in selected brain areas of young (2-week-old) rats. In the inferior olive and the hypoglossal nucleus, angiotensin II binding to AT2 receptors was insensitive to 5 mM dithiothreitol. Conversely, in the ventral and mediodorsal thalamic, medial geniculate, and oculomotor nuclei, the superior colliculus and the cerebellar cortex, incubation with 5 mM dithiothreitol significantly decreased angiotensin II binding to AT2 receptors to about 40% of control. These data suggest that brain AT2 receptors are heterogeneous with respect to their sensitivity to sulfhydryl reducing agents. PMID- 1639113 TI - TMB-8 (8-(N,N-diethylamino) octyl-3,4,5-trimethoxybenzoate) inhibits the ATP sensitive K+ channel. AB - Whole-cell current clamp, single-channel recordings and 86Rb+ flux techniques have been used to show that 8-(N,N-diethyl-amino)octyl-3,4,5-trimethoxybenzoate (TMB-8) inhibits ATP-sensitive K+ channels in HIT-T15 beta-cells. TMB-8 inhibition is observed when KATP channels are activated by ATP depletion or by the K+ channel opener, diazoxide. PMID- 1639114 TI - Monoclonal antibodies to the nonpeptide angiotensin II receptor antagonist, losartan. AB - Two murine monoclonal antibodies were produced to losartan (DuP 753), a nonpeptide angiotensin II receptor antagonist. Using a solid phase competitive enzyme-linked immunosorbent assay (ELISA), each antibody was examined for its ability to bind to a set of losartan analogs that differ structurally in varying degrees. Both antibodies distinguished fine structural changes in the analogs, particularly at the R5 position of the imidazole ring. No cross-reactivity towards either antibody was observed with the natural ligand angiotensin II, the peptide antagonist saralasin, or the AT2 selective nonpeptide antagonist PD123177. PMID- 1639115 TI - The molecular pharmacology of L-deprenyl. AB - L-Deprenyl, the selective inhibitor of monoamine oxidase type B (MAO-B), has gained wide acceptance as a useful form of adjunct therapeutic drug in the treatment of Parkinson's disease. This review summarizes the molecular pharmacology of L-deprenyl, and the advances in our understanding of its possible mode of action in Parkinson's disease. L-Deprenyl belongs to the class of enzyme activated irreversible inhibitors also described as 'suicide' inhibitors, because the compound acts as a substrate for the target enzyme, whose action on the compound results in irreversible inhibition. L-Deprenyl first of all forms a noncovalent complex with MAO as an initial, reversible step. The subsequent interaction of L-deprenyl with MAO leads to a reduction of the enzyme-bound flavin-adenine dinucleotide (FAD), and concomitant oxidation of the inhibitor. This oxidized inhibitor then reacts with FAD at the N-5-position in a covalent manner. The observed in vitro selectivity of L-deprenyl for MAO-B may be accounted for by differences in the affinities of the two MAO subtypes for reversible interaction with L-deprenyl, differences in the rates of reaction within the noncovalent complexes to form the irreversibly inhibited adduct, or a combination of both these factors. However, if selective inhibition is to be maintained in vivo, correct dosage schedules are critically important, since all selective MAO inhibitors described up to now lack selectivity at high doses. In experimental animals L-deprenyl is protective against the damaging effects of several neurotoxins, including the dopaminergic agents 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) and the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4). Beside MAO-B inhibition, which above all explains the prevention of neurotoxic action of MPTP by preventing its metabolism, L-deprenyl appears to exhibit other mechanisms of action which are independent of its action on MAO-B. PMID- 1639116 TI - Increased prevalence of proliferative retinopathy and cardiovascular autonomic dysfunction in IDDM patients with proteinuria. AB - The purpose of the present cross-sectional clinical study was to evaluate the prevalence of retinopathy in Type 1 diabetic patients without nephropathy and with different degrees of nephropathy. In addition we investigated the association between retinopathy, nephropathy, and other variables, and studied the importance of cardiovascular autonomic dysfunction to these conditions. 76 Type 1 diabetic patients were investigated. All patients were initially selected on the basis of body weight, and 47 proteinuric patients were further selected for age, diabetes duration and the duration of insulin treatment (see Table 1). Proteinuric diabetic patients were categorized by degree of nephropathy, i.e. for incipient nephropathy (proteinuria of less than 0.5 g/day), for overt nephropathy (proteinuria of more than 0.5 g/day), and for renal failure (serum creatinine of more than 103 mumol/l). Retinopathy was assessed by ophthalmoscopy. Cardiovascular autonomic dysfunction (CAD) was assessed by heart rate variations, 30:15 ratios, the Valsalva maneuver, and systolic blood pressure fall upon standing. Our findings revealed increased prevalence of retinopathy in patients with more advanced stages of nephropathy. CAD abnormalities exhibited increased prevalence among proteinuric patients. Our data clearly revealed differences between proteinuric and non-proteinuric patients. In both proteinuric and non proteinuric patients there were found correlations of retinopathy with diabetes duration, and only in proteinurics was retinopathy correlated with kidney function, systolic blood pressure and CAD findings. In patients in identical stages of nephropathy, increased prevalence of CAD abnormalities was shown in patients suffering from proliferative retinopathy. Thus our data suggest that CAD abnormalities might be related in some way to both the proliferative retinopathy and to diabetic nephropathy. PMID- 1639117 TI - Influence of the electrical stimulation of the hypothalamus on adrenocortical steroidogenesis in hypophysectomized rats. AB - The electrical stimulation of the ventromedial hypothalamus (VMH), lateral hypothalamic area (LHA), periventricular arcuate nucleus (ARC), and posterior hypothalamus (PHY), on 14C transfer rates from 14C-1-acetate into adrenocortical steroids in adrenal slices of hypophysectomized rats were investigated. The 14C transfer rates into corticosterone and cortisol were increased by the stimulation of the VMH, ARC, and PHY, but decreased by the stimulation of the LHA. From these results, it might be suggested that these hypothalamic structures were involved in the regulation of adrenocortical steroidogenesis without participation of the pituitary. PMID- 1639118 TI - Clinical and experimental diabetes are associated with an impairment of peripheral nerve function. PMID- 1639119 TI - Cyclic changes of exopeptidase activities in the rat brain: a regional study. AB - The present report describes the activity of three neuropeptide-degrading enzymes, in 12 brain areas during the estrous cycle of Sprague-Dawley rats. The quantitation of the enzyme activities was performed by measuring the rate of hydrolysis of the chromogenic substrates Leu-, Lys- and Asp-2-naphthylamides, by neutral, basic and acid aminopeptidase (AP) activities, respectively. Lys- and Leu-AP activities show a significant increase during the proestrus stage in the hypothalamus and the pituitary gland. Also there is a significant increase of Leu AP activity in the occipital cortex. No significant decreases for Asp-AP activity during the proestrus in the hypothalamus and the pituitary were observed. As the changes seem to be limited at the hypothalamic-pituitary axis, these findings could be interpreted to mean that these exopeptidase activities play a role in the hormonal changes that take place during the estrous cycle of the rat. PMID- 1639120 TI - The correlation of serum prolactin level and psychic stress in women undergoing a chronic hemodialysis programme. AB - Altogether eight women undergoing a chronic hemodialysis treatment were studied for five months. Four of them were in the premenopause and four in the postmenopause. Once a month levels of prolactin, FSH, LH, estradiol and progesterone were measured, Luscher colour test was performed, from which the screamer index as an indicator of psychic stress was calculated and the levels of urea, creatinine and hematocrite were assessed to inform us of the adequacy of dialysis. We tested the hypothesis, whether there exists a correlation between psychic stress and the prolactin level in these women. For statistic evaluation we used linear regression under the use of dummy variables to intercept the interindividual differences in the Luscher test. We found that the fluctuation of the prolactin level and of the value of the screamer index of the Luscher test are parallel (p less than 0.05). These results bear witness of a participation of psychic stress in the onset and level of hyperprolactinemia in women being in a chronic hemodialysis treatment. PMID- 1639121 TI - Somatomedin-C/IGF-I, insulin and prolactin levels in Ullrich-Turner's syndrome. AB - To clarify the pathogenesis of growth retardation in patients with Ullrich Turner's syndrome (TS) we have investigated basal SmC/IGF-I, insulin and prolactin concentrations. Compared with 56 age matched healthy controls basal SmC/IGF-I concentration in 51 patients with TS older than 9-11 years was significantly lower (age group 13-14 years; TS 273 +/- 47 and controls 479 +/- 114 ng/ml). Mean basal prolactin level in 43 patients with TS (406 +/- 211 microU/ml) was significantly higher (p less than 0.01) than in 192 female controls (age 3-11 years; 264 +/- 176 microU/ml). Basal insulin concentration in 28 TS patients in comparison to 20 healthy children of a control group was significant higher (TS 18 +/- 8 microU/ml; controls 9 +/- 4 microU/ml; p less than 0.01). It seems that neither insulin nor prolactin are relevant stimulators of Smc/IGF-I in man, especially in patients with gonadal dysgenesis. Considering these results we speculate that despite higher prolactin and higher insulin levels in TS, the lower SmC/IGF-I concentrations may be predominantly related to the abnormal sex steroid secretion. PMID- 1639122 TI - Effects of acetylcholine on the release of thyrotropin-releasing hormone from the rat retina in vitro. AB - Effects of acetylcholine on the release of thyrotropin-releasing hormone (TRH) from the rat retina were studied in vitro. The retina was incubated in medium 199 (pH 7.4) with 1.0 mg/ml of bacitracin and 100 micrograms/ml of ascorbic acid (medium) for 20 min. The amount of TRH release into the medium was measured by radioimmunoassay. The TRH release from the rat retina was enhanced significantly in a dose-related manner with the addition of acetylcholine and inhibited with addition of atropine. The stimulatory effect of acetylcholine on TRH release from the retina was blocked with the addition of atropine. The elution profile of methanol-extract of the rat retina was identical to that of synthetic TRH. The findings suggest that the cholinergic system stimulates TRH release from the rat stomach in vitro. PMID- 1639123 TI - Serum parathyroid hormone and calcitonin levels following ovariectomy in the adult rat. AB - The ovariectomized rat is a reasonably good and often utilized model of human post-menopausal osteoporosis (Devlin and Ferguson, 1989). Mature rats were either ovariectomized or underwent a sham operation, killed at intervals following operation and the serum concentration of parathyroid hormone and calcitonin at death related to the histomorphometry of the cancellous bone of the proximal ilium. The mean serum calcitonin concentration for all ovariectomized rats was 66.4 pg/ml (SD = 18) and for the control rats was 76.42 pg/ml (SD = 20). The serum calcitonin concentration in the ovariectomized rats was significantly negatively correlated with the extent of erosion cavities of the cancellous bone (r = -0.598, t = -2.36, p = 0.039). No significant correlation was observed for the control rats (r = -0.107, t = -0.357, p = 0.727). The mean extent of erosion cavities in the ovariectomized group was 6.81% (SD = 1.94) and in the control group was 6.47% (SD = 2.21), with no significant differences between the two groups (t = 0.41, p = 0.69). No significant correlations were observed in serum parathyroid hormone (PTH) concentration with the bone resorption parameters. From this study it was concluded that calcitonin may be of aetiological importance in bone loss in the ovariectomized rat. PMID- 1639124 TI - Serum urate and renal function in different forms of hypercalcemia. AB - In order to investigate the relationships between serum calcium, urate and kidney function, serum calcium, urate, creatinine and urea were measured at 100 occasions in hypercalcemic cancer patients together with 113 preoperative measurements in HPT subjects and 106 measurements in normocalcemic control persons. When compared to normocalcemic control subjects (serum urate 336 +/- 110 mumol/l) both HPT subjects (356 +/- 98 mmol/1, p less than 0.006) and the cancer patients (407 +/- 179 mmol/l, p less than 0.001) showed raised levels of serum urate. While serum urate was correlated to serum creatinine in all groups (r = 0.40-0.59, p less than 0.0001) a significant correlation to serum calcium was only seen in the HPT group (r = 0.28, p less than 0.004). This relation persisted also after correction for age, sex and serum creatinine in the multiple regression analysis. Serum creatinine was similar in all groups but significantly correlated to serum calcium only in the HPT subjects (r = 0.29, p less than 0.003). Serum urea was not significantly correlated to serum calcium in any of the groups but was elevated in the cancer group (8.3 +/- 4.4 vs 6.2 +/- 2.9 mumol/l in the control group, p less than 0.0001). This elevation in serum urea seen in the cancer patients might rather be explained by dehydration or catabolism than an impaired kidney function. In conclusion, while serum urate is related to the kidney function both in normo- and hypercalcemia, it also seems to be related to the hypercalcemia in HPT subjects but not in cancer patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639125 TI - Lifelong enhanced diabetes susceptibility and obesity after temporary intrahypothalamic hyperinsulinism during brain organization. AB - Newborn male Wistar-rats received bilateral intrahypothalamic insulin-agar implants on the 2nd or 8th day of life. In male control animals only the insulin free indifferent agar-vehicle was implanted at the same age. In both experimental groups with temporary intrahypothalamic hyperinsulinism during brain organization the following results were obtained: 1) Higher body weight gain starting at the end of the hypothalamic differentiation period and continuing during juvenile life until adulthood, resulting in increased relative body weight as a sign of obesity; 2) A tendency to basal hyperinsulinaemia in juvenile and adult age; 3) Impaired glucose tolerance in adulthood; 4) Increased diabetes susceptibility to a single "subdiabetogenic" dose of streptozotocin in adult age. In view of these and previous observations a teratogenetic role of high insulin concentrations during the organization of glucoregulatory hypothalamic structures is hypothesized and the possible relevance of such hyperinsulinism as a predisposing factor for a lifelong enhanced diabetes and/or obesity risk is suggested. PMID- 1639126 TI - Hypothermia in insulin-treated obese rats. AB - Changes of colonic temperature were investigated to examine a mechanism of hypothermia in the obese rats which received subcutaneous administration of intermediate type-insulin (8 U/day) for 8 weeks. Although diurnal rhythmicity of colonic temperature levels was maintained similarly with those of vehicle injected controls, the overall colonic temperature levels were significantly lowered in insulin-treated animals. In the condition of cold exposure at 5 degrees C, colonic temperature levels of insulin-treated animals were immediately and significantly decreased at 60 minutes after the start of cold exposure. The data obtained herein demonstrated that hyperinsulinemia accompanying with hyperphagia should be profoundly involved in hypothermia, observed in various experimental models of obesity. PMID- 1639127 TI - Colonic temperature was not changed in the development of obesity after ovariectomy. AB - We tested the hypothesis that altered heat production ability after ovariectomy may be involved in the development of obesity. Two weeks after ovariectomy, food intake of ovariectomized (Ovx) rats was increased and body weight gain was obvious, compared with sham-operated animals. However, colonic temperature of Ovx rats was not different from that of sham-operated animals. Food intake of Ovx rats was similar with that of sham-operated rats at 8 weeks later. In this period, colonic temperature of Ovx rats was not different from that of sham operated animals and diurnal rhythmicity was maintained. The present data suggested that changes in heat production may be not an important inducer of obesity in both the dynamic and static phases of the development of obesity after ovariectomy. PMID- 1639128 TI - Immortalization of murine primary spleen cells by v-myc, v-ras, and v-raf. AB - Growth factor-independent cell lines, including four lines characterized as macrophages, were isolated by infection of BALB/c mouse primary spleen cells with combinations of three retroviruses encoding v-myc, v-ras, and v-myc/v-raf. Proliferating cell lines were isolated only rarely, and after long crisis periods, following the introduction of myc and raf by infection with J2 virus, or of myc and ras by coinfection with myc309 and raszip6 viruses. However, sequential infections with all three viruses--myc plus ras cells reinfected with J2, or J2 followed by myc plus ras coinfection--resulted in rapid outgrowth of cell lines which grew at high growth rates to high densities. When cells were treated with anti-IgG F(ab')2/IL-4/IL-5 to specifically stimulate B cells, cell lines were isolated readily by infection with myc plus ras alone, J2 alone, or all three viruses. These cell lines arose after shorter crisis times and all grew at high growth rates and to high densities. Analysis of cell surface markers and immunoglobulin gene arrangement revealed no lymphoid characteristics in any of the lines. Four cell lines express all three macrophage markers analyzed (F4/80, Mac1, FcR), and many others are Mac1+ and/or FcR+. Out of 20 immortalized cell lines tested, 13 show clonal growth in soft agar, and 3/6 of these produced tumors in BALB/c mice, indicating that fully transformed cells may be isolated by these procedures. In at least one of the cell lines, integration of all three infecting viruses has occurred. PMID- 1639129 TI - Formation of primary constriction and heterochromatin in mouse does not require minor satellite DNA. AB - Whereas the major satellite fraction in mouse extends its domain from the centromere to the distal end of the pericentric heterochromatin, the minor satellite DNA is present specifically in the centromere or primary constriction. We hybridized the biotinylated minor satellite sequence to L929 cells of mouse origin. The sequence hybridized to all chromosomes. Whereas hybridization was detected on all active centromeres, the inactive centromeres in certain dicentrics did not show any signal. This satellite, however, was detected in all inactive centromeres in a heptacentric chromosome. The intensity of fluorescence on the inactive centromeres of the heptacentric was similar to that present on the active centromeres. Several heterochromatin blocks, which were not associated with any centromere, were also found to lack hybridization with the minor satellite. The inactive centromeres, whether carrying the minor satellite DNA fraction or not, generally do not react with the antikinetochore antibodies present in the scleroderma serum. These studies are interpreted to show that (1) the primary constriction in mouse can be formed without the participation of minor satellite, (2) heterochromatin in mouse may constitute without this fraction, (3) the major and minor satellite may not be interspersed but are joined at some defined boundary, and (4) the binding of CENP-B does not depend upon the quantity of minor satellite or the number of CENP boxes present in the inactive centromeres. PMID- 1639130 TI - Transformation and characterization of mutant human fibroblasts defective in peroxisome assembly. AB - Human skin fibroblasts deficient in peroxisome biogenesis were transformed by transfecting SV40 ori- DNA with the use of an electroporator, and the biochemical, immunocytochemical, and cytogenetic properties of the transformants were analyzed. Cells (1 x 10(6)) from a patient with Zellweger syndrome and one with neonatal adrenoleukodystrophy were suspended with 2 micrograms of SV40 ori- DNA in PBS; then a high-voltage pulse (2000 V, 30 microseconds) was generated two times. Several colonies expressing large T-antigen were picked up 4 weeks after transfection. Doubling time of the transformants was about half of that and the saturation density was 5 to 10 times greater than that of the parental cells. Biochemical abnormalities including defective lignoceric acid oxidation, dihydroxyacetone phosphate acyltransferase deficiency, and disturbed biosynthesis of peroxisomal beta-oxidation enzymes were preserved in the transformants. Peroxisomes were defective in all colonies, as determined by immunofluorescence staining using anti-catalase IgG. Cell fusion studies confirmed that the transformants belong to the same complementation groups as those of the parental cells. These transformed mutant cell lines are expected to be useful tools for investigating the pathogenesis of inherited diseases related to defects in peroxisome biogenesis. PMID- 1639131 TI - Biogenesis of endoplasmic reticulum transport vesicles transferring gastric apomucin from ER to Golgi. AB - Rough endoplasmic reticulum (RER) transport vesicles were generated from gastric mucous cell RER microsomes in the presence of labeled precursors of phospholipids. The vesicles contained 7-10% of their proteins in the form of apomucin (cargo), and 80% of de novo synthesized phosphatidylcholine (PC) was incorporated into the vesicular membrane. In the absence of choline and ethanolamine precursors or in the presence of 3 mM N-ethylmaleimide (NEM), an inhibitor of CTP:phosphocholine cytidylyltransferase, formation of the transport vesicles, their enrichment in the newly synthesized PC, and the total synthesis of PC decreased by 86%, whereas in the presence of 3 mM Zn2+, complete blockage of vesicle formation and PC synthesis was observed. Analysis of the mucin transporting vesicles indicated that the CTP:phosphocholine cytidylyltransferase and 1,2-diacyl-sn-glycerol:CDP-choline phosphotransferase remained associated with transport vesicles released from ER. The enzymes and other proteins separated from the vesicle surface prior to vesicle fusion with Golgi and the process was induced by phosphorylation. Based on the results of this study, it is proposed that the formation of the ER transport vesicles of gastric mucosal cells is in concert with synthesis of phospholipids and thus in part is regulated by phospholipid-synthesizing enzymes that reside on the membrane during its biogenesis and dissociate from its surface once the task is completed. PMID- 1639132 TI - Colonic cancer cell (HT29) adhesion to laminin is altered by differentiation: adhesion may involve galactosyltransferase. AB - The effects of cell differentiation on cell adhesion to laminin were studied using the human colon tumor cell line, HT29. HT29 cells were induced to differentiate either by glucose deprivation (HT29glc- vs HT29glc+) or by 2 mM butyrate (HT29glc-+B+). Adhesion was assayed after incubating cell suspensions in microtiter wells previously coated with laminin or other substrates. HT29glc+ cells adhered preferentially to laminin over BSA, fibronectin, and ovalbumin. The adhesion to laminin was greater than 50% of maximum within 15 min. HT29glc- cell adhesion to laminin was consistently lower than that for HT29glc+ or HT29glc+B+ cells. alpha-Lactalbumin (ALA), a modifier of galactosyltransferase (GT) substrate specificity, caused a significant reduction (greater than 50%) in HT29glc+ cell adhesion to laminin when ALA was added to the adhesion incubation mixture. Addition of glucose+ALA to the suspension restored adhesion to laminin. Ovalbumin, a GT substrate, increased adhesion of HT29glc+ and HT29glc- cells to laminin, but lactose, a GT product, did not. The data show that undifferentiated HT29 cells adhere preferentially to laminin over fibronectin and collagen IV and that differentiation of HT29 cells reduces adhesion to laminin. In addition, the data imply that cell adhesion to laminin may be mediated by factors that also modify galactosyltransferase activity. PMID- 1639133 TI - Disruption of microtubules inhibits the stimulation of tissue plasminogen activator expression and promotes plasminogen activator inhibitor type 1 expression in human endothelial cells. AB - The expression of certain proteolytic enzymes involved in cell migration (collagenase, urokinase) can be enhanced by the disruption of cellular cytoskeletal organization, suggesting an association between cell shape and gene expression. We have examined the effect of cytoskeleton-disrupting agents on the production and secretion of another proteolytic enzyme, tissue plasminogen activator (tPA), and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), in human endothelial cells. Addition of 1 x 10(-6) M colchicine, 5 x 10(-6) M cytochalasin B, 10(-6) M nocodazole, or 10(-6) M tubulazole had no effect on the constitutive rate of release of tPA. However, the three microtubule-disrupting agents--colchicine, nocodazole, and tubulazole--depressed the stimulation of tPA secretion by phorbol myristate acetate (PMA) by 50- to 65%. Disruption of microfilament structure by cytochalasin B had no effect. In contrast, microtubule disruption in the absence or presence of PMA stimulated PAI-1 secretion by 2.5 and 2 times, respectively. The depression of tPA secretion was not due to inhibition of the secretory function since tPA did not accumulate intracellularly during colchicine treatment. Nor did colchicine affect the PMA activation of protein kinase C-alpha, upon which stimulation of tPA is dependent; neither translocation of the kinase nor phosphorylation of the protein kinase C substrate protein, P80, was inhibited. Measurement of tPA mRNA levels demonstrated that the increase which precedes PMA-enhanced tPA secretion was also inhibited by colchicine by 50%. However, tPA gene transcriptional activity was only reduced 13%, suggesting that a post-transcriptional event was affected by microtubule disruption. PAI-1 mRNA levels and transcription rates were elevated 3.5 times. This study suggests that the changes that occur in endothelial cells during PMA induced signal transmission leading to enhanced tPA mRNA levels and tPA antigen production can be partly blocked by agents that disrupt microtubule organization. PMID- 1639134 TI - The use of caged substrates to assess the activity of 6-phosphogluconate dehydrogenase in living sea urchin eggs. AB - As part of our inquiries into the regulation of the hexose monophosphate shunt in the early development of sea urchin eggs and embryos, we have developed a novel method to assess the in vivo activity of the enzyme 6-phosphogluconate dehydrogenase (6PGDH) before and after fertilization. Our measurements show that the intracellular level of 6-phosphogluconate (6PG) in eggs decreases 60% after fertilization, which is consistent with the increase in the activity of 6PGDH previously reported using irreversibly permeabilized cell assays (Swezey and Epel, Proc. Natl. Acad. Sci USA 85, 812-816, 1988). The in vivo turnover of the 6PG pool was assessed using a new radioisotopic technique. 1-14C-labeled 6PG was chemically modified such that it was not metabolized by cellular 6PGDH and could be rapidly converted back to 6PG by photolysis. This "caged" 6PG was introduced into unfertilized sea urchin eggs using a transient permeabilization procedure, and then the oxidation of [1-14C]6PG in vivo upon irradiation was followed. Oxidation of 6PG was complete within 7-11 s of irradiation, indicating an extremely rapid turnover of this pool in sea urchin eggs. Based on the 6PG pool sizes and the kinetic properties of 6PGDH, determined here, along with the activity levels seen in permeabilized cells, the half-time for the label in the 6PG pool in sea urchin eggs is calculated to be 26 s. This is inconsistent with the in vivo turnover rates seen in these studies, indicating that the permeabilized cell assays overestimate the degree of inhibition of 6PGDH before fertilization. These results suggest that caution should be exercised in extrapolating data obtained from permeabilized cells to the situation in vivo. PMID- 1639135 TI - Lithium mimics dexamethasone in stimulating DNA synthesis by WI-38 cells. AB - Lithium interferes with the responses of neural and secretory cells to calcium mobilizing agonists by blocking the generation of phospholipase C-dependent second messengers. However, the mechanism by which lithium stimulates the proliferation of other cells in response to agonists that do not activate phospholipase C remains obscure. We investigated the pathways that mediate the mitogenic action of lithium on WI-38 cells in a defined, serum-free medium. Lithium, like dexamethasone (Dex), potentiated DNA synthesis in response to the combination of insulin+epidermal growth factor (EGF) (+50%), but not in response to either growth factor alone or with Dex. As in the case of Dex, lithium could be added as late as 8 h following stimulation of quiescent cells by insulin+EGF without loss of potentiating activity. While DNA synthesis in control cultures was essentially complete by 24 h, lithium and Dex stimulated "late" DNA synthesis (24-30 h) 10-fold and 5-fold, respectively. The potentiating activity of Dex, but not that of lithium, was blocked by the specific glucocorticoid receptor antagonist, RU486. Both lithium and Dex stimulated log-phase growth, but only Dex increased saturation density. These data indicate that both lithium and Dex recruit into the cell cycle a subpopulation of cells with a longer mean prereplicative phase (G1). The effect of lithium on DNA synthesis in WI-38 cells may be mediated by the glucocorticoid response pathway at some point distal to activation of the glucocorticoid receptor, or by an independent mechanism that can be switched on late in G1. PMID- 1639136 TI - The autoantigen La/SSB: detection on and uptake by mitotic cells. AB - The nuclear autoantigen La, a transcription/termination factor of RNA polymerase III, was recently shown to translocalize to the cell surface of growth-stimulated cells during transition from G0- to G1-phase. Here we describe the staining of living mitotic cells with the anti-La mab La11G7. Moreover, La protein added to cell culture medium was able to enter into synchronized mitotic cells. Uptake was inhibited by the anti-La mab. La protein taken up into prophase cells assembled into a fibrillar network. Taken up byu ana/telophase cells, La protein was preferentially transported into the newly forming or formed nuclei. This import allowed us to study directly the intranuclear localization of La protein in living cells by the use confocal laser scanning microscopy (cLSM). Adsorbed La protein was found in the nucleoplasm but also assembled into nuclear speckles. Some of these speckles surrounded the nucleolus like a ring. PMID- 1639137 TI - Reorganization of the endocytic compartment in regenerating liver. AB - Antibodies raised to two membrane proteins present in rat liver endosomal fractions were used to study changes occurring in the endocytic compartment of hepatocytes during liver regeneration. Antibodies to the 42-kDa subunit (RHL-1) of the asialoglycoprotein receptor showed, by Western blotting of liver microsomes and endosomes, that there was a reduced expression of the receptor in liver 24 h following a partial hepatectomy. Immunocytochemical staining of thin sections of regenerating livers using these antibodies indicated that there was an intracellular relocation of endocytic structures in hepatocytes. The two main endocytic regions immunocytochemically stained in normal liver--one located beneath the sinusoidal plasma membrane and the other abutting the bile canaliculus--were replaced, in regenerating liver, by staining more closely associated with a region underlying the baso-lateral plasma membrane. A 140-kDa pI 4.3 calmodulin-binding protein located in endocytic and plasma membranes was also demonstrated, using a radio-iodinated calmodulin-binding assay, to be present at reduced levels in endosomes isolated from regenerating livers. Antibodies to this calmodulin-binding protein stained the hepatocyte's cytoplasm in a punctate manner. However, in regenerating liver, the staining was located in regions underlying the baso-lateral and apical plasma membrane of hepatocytes. Together, the results demonstrate that a reorganization of the endocytic compartment has occurred in hepatocytes 24 h following hepatectomy, with two endosomal proteins becoming relocated to a region below the baso-lateral-apical surface regions of hepatocytes. PMID- 1639138 TI - Adenovirus capsid proteins interact with HSP70 proteins after penetration in human or rodent cells. AB - Soon after penetration of adenovirus serotype 2 in BHK-21 and HeLa cells, HSP70 and HSC70 proteins become associated with the viral capsid. By analysis with a polyclonal antibody derived from a fusion protein containing the C-terminal domain, 290 amino acids of HSP70, and using both immunological methods and infected cells fractionation we observed that a significant amount of HSP70 proteins moved to the nucleus and colocalized with the adenovirus particles. HSP70 proteins of infected cells were isolated as a complex cross-linked with intracytoplasmic adenovirus type 2. By coprecipitation, using a polyclonal specific antiserum derived from the fusion protein, or two different monoclonal specific antisera, we showed that HSP70 and HSC70 proteins were associated with hexon, the major adenovirus capsid protein. PMID- 1639139 TI - Immunolocalization of Ku-proteins (p80/p70): localization of p70 to nucleoli and periphery of both interphase nuclei and metaphase chromosomes. AB - Distribution on both nuclei and metaphase chromosomes of Ku-proteins, recognized by autoantibodies from a patient with systemic lupus erythematosus, has been studied using a specific monoclonal antibody (mAbH6) that recognizes p70, one Ku protein. Observation with either a conventional fluorescent microscope or a confocal laser scanning microscope revealed mAbH6-stained p70 antigen localized on both nuclear periphery and nucleoli of human interphase cells. The specific staining of nucleoli with mAbH6 has been confirmed using isolated nucleoli from rat liver in which the staining was seen as fine granules surrounding nucleolar DNA. During mitosis p70 antigen moved away from association with the nuclear envelope region to localization on the periphery of condensed chromosomes with no apparent staining of chromosome interior. The p70 antigen was copurified with DNA fragments by immunoaffinity column chromatography using mAbH6. The mAbH6 staining of both nuclear periphery and nucleoli was lost upon digestion with DNase I at low concentrations. These results suggest that p70 antigen is connected with these nuclear structures through DNA. PMID- 1639140 TI - Gap junctional communication of primary human keratinocytes: characterization by dual voltage clamp and dye transfer. AB - We have compared dye coupling in pairs of small (less than 10 microns in diameter) and large (greater than 20 microns in diameter) keratinocytes isolated from normal human epidermis, using Lucifer yellow microinjection. Under control conditions, dye coupling was found in only 1 out of the 25 small pairs tested, whereas it was evident in 75% of the large pairs (n = 52). After a 30-min incubation of the latter pairs in the presence of 10(-6) and 10(-4) M all transretinoic acid (RA), the percentage of coupling was 53% (n = 15; NS) and 7% (n = 14; P less than 0.001), respectively. The almost complete uncoupling observed after 10(-4) M RA was not reversible even 30 min after return to control medium (n = 8). Dual whole-cell patch-clamp recordings from large keratinocyte pairs showed a macroscopic junctional conductance (gj) of 9 +/- 2 nS (n = 43), which was abolished by heptanol (3.5 mM) in a fully reversible way. Compared to heptanol, 10(-4) M RA abolished keratinocyte gj more slowly and irreversibly (n = 10). By contrast, 10(-6) M RA had no significant effect on gj (n = 8). Single-gap junctional channels were also identified between large keratinocytes. Events histograms of 152 transitions from three experiments revealed three main unitary conductances (gamma j) of 45 +/- 4, 78 +/- 4, and 106 +/- 7 pS. The dye coupling results indicate that junctional communication is markedly different in pairs of small and large cells, which showed the phenotype and keratin markers of basal and suprabasal keratinocytes, respectively. In the latter cell type, coupling is ensured by channels of three sizes and is blocked irreversibly by pharmacologic concentrations of RA. PMID- 1639141 TI - The effect of in vitro heat exposure on the recovery of nuclear matrix-bound DNA polymerase alpha activity during the different phases of the cell cycle in synchronized HeLa S3 cells. AB - HeLa S3 cells were synchronized by a double thymidine block or aphidicolin treatment and the levels of nuclear matrix-bound DNA polymerase alpha activity were then measured using activated calf thymus DNA as template. The nuclear matrix was obtained by 2 M NaCl extraction and DNase I digestion of isolated nuclei incubated at 37 degrees C for 45 min prior to subfractionation. In all phases of the cell cycle 25-30% of nuclear DNA polymerase alpha activity remained matrix-bound, even when cells were in the G1 phase. No dynamic association of DNA polymerase alpha activity with the matrix was seen, at variance with previous results obtained in regenerating rat liver. The variations measured in matrix bound activity closely followed those detected in isolated nuclei throughout the cell cycle. If nuclei were not heat-stabilized very low levels of DNA polymerase alpha activity were measured in the matrix (1-2% of total nuclear activity). Heat incubation of nuclei failed to produce any enrichment in matrix-associated newly replicated DNA, whereas the sulfhydryl cross-linking chemical sodium tetrathionate did. Therefore the results obtained after the heat stabilization procedure do not completely fit with the model that envisions the nuclear matrix as the active site where eucaryotic DNA replication takes place. PMID- 1639142 TI - Conventional and confocal microscopic studies of insulin receptor induction in Tetrahymena pyriformis. AB - Tetrahymena pyriformis reportedly possesses binding structures for the vertebrate hormone insulin that are amplified in cells having prior exposure to the hormone. Conventional and confocal microscopic studies were conducted to verify the validity of the reports and to localize the binding sites. Logarithmic cultures were exposed to insulin concentrations of 0, 3, 6, and 12 micrograms/ml for 1 h (receptor induced, RI). After an additional culture period the cells were fixed, exposed to porcine insulin (antigen), immunocytochemically processed, and examined for staining intensity by video image analysis. Observations indicate that T. pyriformis does bind insulin whether or not the cells have prior exposure to insulin. Staining intensity increased at the two highest RI concentrations over 0 microgram/ml (P less than 0.01) but the staining intensity at 0 microgram/ml was not different from that at 3 micrograms/ml. The results confirm that T. pyriformis does bind insulin and that prior exposure to insulin increases the binding capacity for insulin in what may be a concentration-dependent manner. Confocal microscopy of RI cells that had been labeled with either fluorescein isothiocyanate-insulin or the immunocytochemical technique outlined above revealed labeling of the cytoplasm that appeared to be vesicular. Both techniques produced very similar labeling patterns when optical sections through the cells were viewed. Conventional fluorescence revealed ciliary labeling that could be decreased by incubation with excess unlabeled insulin. Further studies with the exo- mutant of T. thermophila, SB 255, showed that mucocyst discharge and capsule formation are not involved in insulin binding. PMID- 1639143 TI - Reorganization of the cytoskeleton and morphological changes induced by 1,25 dihydroxyvitamin D3 in C3H/10T1/2 mouse embryo fibroblasts: relation to inhibition of proliferation. AB - The effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) on cell morphology, the cytoskeleton, and fibronectin were studied in three lines of C3H/10T1/2 mouse embryo fibroblasts in which the antiproliferative effect of the hormone had previously been investigated. We showed that 1,25(OH)2D3 induced morphological changes in the nontransformed C3H/10T1/2 Cl 8 cells, which flattened and spread out markedly. Visualization of actin and tubulin by immunocytochemistry disclosed a reorganization of the microfilament and microtubular systems. 1,25(OH)2D3 also induced an increase in cell-surface-associated fibronectin. These changes were only slight in the transformed cell line C3H/10T1/2 Cl 16 and absent in the transformed C3H/10T1/2 TPA 482 cell line. These effects were correlated with the growth inhibition induced by the hormone, and this suggests a possible relationship between the 1,25(OH)2D3-induced alterations of cell shape and of the cytoskeleton and the effects of the hormone on cell proliferation. PMID- 1639144 TI - Overexpression of the two-chain form of cathepsin B in senescent WI-38 cells. AB - We have examined differential protein expression in serum-stimulated young and senescent WI-38 human fetal lung-derived cells in culture using high-resolution two-dimensional gel electrophoresis. Overexpression of a protein with an approximate M(r) of 29,000 and pI of 5.8 was observed in senescent cells during the G0 and throughout the G1 stage of the cell cycle. Automated amino-terminal sequencing of the peptide from polyvinylidene difluoride electroblots showed 100% sequence identity to cathepsin B or pre-procathepsin B in a 12-amino acid overlap, beginning at residue 48 or 129, respectively. The 29-kDa peptide corresponds to the heavy chain of the two-chain enzyme form. Cathepsin B activity was found to be decreased in cells aged in vitro in comparison to that in young controls. Changes in the steady-state levels of both the 4.0- and the 2.2-kb cathepsin B transcripts between young and senescent cells cannot account for the overexpression of the two-chain form of the enzyme. These results suggest that increased proteolysis of a conformationally more labile single-chain form and/or decreased turnover and accumulation of a less active form of this lysosomal protease occur in senescent fibroblasts and may account for the observed decreased cathepsin B activity in senescent cells in culture. PMID- 1639146 TI - Increased histone H1(0) expression in differentiating mouse erythroleukemia cells is related to decreased cell proliferation. AB - The amount of histone H1(0) increases relative to other H1 subtypes in terminally differentiated cells, and its expression has been associated with the onset of differentiation. We have studied the kinetics of H1(0) accumulation in mouse erythroleukemia (MEL) cells and found that the levels of H1(0) reflect the rate of cell proliferation rather than the state of differentiation. This suggests that changes in the relative amount of H1(0) during MEL cell differentiation are primarily a consequence of cell cycle arrest. PMID- 1639145 TI - RGD-directed attachment of isolated rat osteoclasts to osteopontin, bone sialoprotein, and fibronectin. AB - Osteoclasts isolated from the long bones of 5-day-old rats were seeded onto glass surfaces coated with osteopontin, bone sialoprotein, or fibronectin. Cell binding was promoted by all three proteins and inhibited in a dose-dependent manner by an RGD-containing peptide, while an RGE-containing peptide was ineffective. Immunocytochemistry of bone tissue showed enhanced concentration of osteopontin in bone opposite the clear zone of the osteoclasts, whereas immunolocalization of bone sialoprotein and fibronectin showed no accumulation on bone surfaces facing cells. The observations corroborate previous findings that the osteoclast is attached via an integrin to osteopontin on the bone surface. Although bone sialoprotein and fibronectin can mediate osteoclast binding in vitro, such a role in vivo is not supported by the immunocytochemical observations. PMID- 1639147 TI - Failure of kinetochore development and mitotic spindle formation in okadaic acid induced premature mitosis in HeLa cells. AB - The mitotic events associated with okadaic acid (OA)-induced premature chromosome condensation (PCC) in S-phase-blocked HeLa cells were studied at the light microscope, immunofluorescence, and electron microscope level. The development of PCC in these cells has been compared with that in multinucleate cells and also in uninucleate hamster cells induced by caffeine. In OA-induced PCC, the nuclear envelope breaks down and chromosomes condense, but the mitotic spindle and trilaminar kinetochores fail to develop. In S-phase PCC in multinucleate cells, only the mitotic spindle does not develop, whereas in caffeine-induced PCC, all these events are found to be associated. The possible difference in their pathways of induction and, in this connection, the dissociability of the early mitotic events have been discussed. PMID- 1639148 TI - Cultured microvascular endothelial cells derived from the bovine corpus luteum possess NCAM-140. AB - Previously, five phenotypically different, stable types of microvascular endothelial cells (MVE) were isolated from the bovine corpus and cultured successfully. We found that three out of these five types of MVE express the neural cell adhesion molecule (NCAM). As shown by immunocytochemistry, weak NCAM immunoreactivity occurred mainly in the perinuclear area of cell type 1. Monolayers of types 2 and 5 revealed heavy NCAM immunoreactivity, which was localized predominantly at the lateral cell surface outlining the contact zones of adjacent cells. In contrast, cell types 3 and 4 were not NCAM immunoreactive. Western blot analyses substantiated these results: While cell type 1 showed a weak immunoreactive band, cell types 2 and 5 displayed strong NCAM-immunoreactive bands of a molecular weight of approximately 140 kDa (NCAM-140), which was absent in cell types 3 and 4. These results reveal for the first time that NCAM can be expressed by cultured MVE and may serve in mediating endothelial cell contacts. Since luteal cells also express NCAM-140, this adhesion molecule could in addition be involved in the interactions of luteal cells with MVE. PMID- 1639149 TI - A historical perspective of research on the biology of aging from Nathan W. Shock. AB - This article describes some of the thoughts and the conceptual framework from which Nathan W. Shock prepared his last major presentation. This paper, written some 8 months following Dr. Shock's death on November 12, 1989, is based upon his extensive notes and discussions with one of the authors (George T. Baker). This presentation in no way is meant to encapsulate the long and distinguished career of Nathan Shock, but rather to provide a glimpse of his perspectives on the development of the field of aging. Furthermore, we believe that the scientific principles concerning aging research laid out by Dr. Shock in this publication are still valid today and may provide valuable insights for researchers in the field. PMID- 1639150 TI - Memory performance of young and old subjects related to their erythrocyte characteristics. AB - Several papers reported in recent years on a change in the age population distribution of the circulating erythrocytes in old mice, rats, rabbits, and humans. The results indicate the presence of a chronologically younger cell population in old animals and humans. The cells are typically lower in density and larger. In some reports, the cells have higher levels of enzymatic activity. We wanted to know whether changes in the characteristics of the circulating erythrocytes in old people are related to the changes in cognitive performance often observed in the elderly. Twenty young (20-40) and 21 old (70-90) volunteers submitted to memory and blood tests. Density and size distribution, aspartate aminotransferase/glutamic oxalacetic transaminase (AST/GOT) activity, and the level of glycosylated hemoglobin (HbA1) of erythrocytes were determined. The Wechsler Memory Scale--Revised (Wechsler, 1987) was used to determine general memory and delayed recall scores for each subject. We have confirmed that old subjects have larger and less dense cells. Erythrocyte volume was the only blood parameter examined that revealed statistically significant correlations with memory performance. The old subjects with no age-related memory impairment had significantly smaller cells than the other old subjects. PMID- 1639151 TI - Aging reduces cardiovascular and sympathetic responses to NTS injections of serotonin in rats. AB - Serotonergic mechanisms for baroreflex modulation could become altered with age. This possibility was explored by comparing cardiovascular and sympathetic effects elicited in 2-month- and 24-month-old rats by injecting serotonin (5-HT) directly into the nucleus tractus solitarius (NTS) which is the primary baroreflex relay station in the medulla. Ensuing decreases in mean pressure, heart rate, and renal nerve firing were significantly smaller in 24-month-old than in 2-month-old rats. By contrast, similar injections into the NTS of the vehicle alone were ineffective in both age groups. Postmortem examination of brain sections showed that NTS injection sites were equally distributed in both age groups, thereby indicating that the brain areas affected by 5-HT were identical regardless of age. Reduced sensitivity of peripheral myocardial beta-adrenergic and vascular alpha-adrenergic receptors was considered partly responsible because 5-HT injected into the NTS lowers blood pressure by decreasing sympathetic vasomotor tone and slows the heart by increasing vagal tone with reciprocal sympatho inhibition. But since reduced adrenergic sensitivity would not account for the concurrent decrease in renal nerve firing, a more logical explanation is that the sensitivity of serotonergic mechanisms in the NTS for inhibiting blood pressure, heart rate, and renal nerve activity decreases with age. PMID- 1639152 TI - Effect of aging and caloric restriction on intestinal permeability. AB - Intestinal permeability is increased in several disorders such as Crohn's disease or rheumatoid arthritis. Since aging leads to alteration of many biological functions, the effect of aging on intestinal permeability was studied by measuring the intestinal permeability in aging rats gavaged with different size permeability probes--mannitol, polyethylene glycol (PEG) 400, and inulin. In rats fed with control diet, there was a significant increase in intestinal permeability to medium size probes PEG 400 (14.8 +/- 0.4 and 21.0 +/- 1.1% at 3 and 28 months respectively, p less than .01) and mannitol (3.41 +/- 0.4 and 5.3 +/- 0.5% at 3 and 28 months, respectively, p less than .01). Intestinal permeability of the large macromolecule inulin did not change (0.42 +/- 0.03 and 0.38 +/- 0.02% at 3 and 28 months, respectively) with aging. There was no correlation between weight of the rats and their intestinal permeability. Because dietary caloric restriction has been found to prolong the life span, retard deterioration of several biological functions, and affect intestinal absorptive functions, we examined the effect of lifelong calorie restriction on intestinal permeability changes. Lifelong calorie-restricted diet did not affect age-related change in intestinal permeability. We conclude that intestinal permeability of medium size probes increases with aging and that lifelong caloric restriction does not prevent this change. We speculate that age-associated deterioration in intestinal barrier functions could permit increased systemic absorption of lumenal antigens and could perhaps contribute to the genesis of antigen-related age-associated diseases. PMID- 1639153 TI - Interaction of aging and lifelong ethanol ingestion on ethanol-related behaviors and longevity. AB - The interactions of aging and long-term voluntary ethanol consumption were studied in the alcohol-preferring AA (Alko Alcohol) rats. The mean daily ethanol intake was 6.45 +/- 0.31 g/kg/day (mean +/- SE) at the beginning of the exposure at 3 months of age. The control animals were given only food and water ad libitum. There was no difference in survival or weight gain between the control and ethanol groups. When tested for voluntary ethanol intake at the age of 24 months, the rats in the ethanol group consumed significantly more ethanol than the controls. The two groups did not differ in ethanol-induced motor impairment, sleep-time, or hypothermia, nor in the rate of ethanol elimination. The 24-month old animals, however, showed higher sensitivity to ethanol than the 3-4-month-old rats in the sleep-time test. It is concluded that the feeding regimen used in this study did not produce any detectable interactions between ethanol and the aging processes in the AA rats. PMID- 1639154 TI - The heterogeneity of the age-related decline in immune response: impairment in delayed-type hypersensitivity and cytotoxic T-lymphocyte activity occur independently. AB - Aged mice are known to have a heterogeneous cytotoxic T-lymphocyte (CTL) response to an influenza challenge. We sought to determine whether delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) was also heterogeneous in aging and, if so, whether this correlated with anti-influenza CTL activity. Aged mice developed mean footpad swelling of 0.24 +/- 0.09 mm following SRBC challenge and mean CTL activity of 35 +/- 18%. Even though these values were significantly lower than those from young mice (0.54 +/- 0.10 mm and 51 +/- 2%, respectively), no correlation was found between anti-influenza CTL activity and DTH to SRBC (r = 0.01). We believe the most likely reason for this independent decline in immune response is because different activation signals are required for DTH and CTL activity. Our data thus suggest an age-related functional mosaicism in the immune system. PMID- 1639155 TI - Trichinella spiralis: modifications of the cuticle of the newborn larva during passage through the lung. AB - A scintigraphic method was developed to study the distribution of radioactivity after iv injection of 131I-labeled Trichinella spiralis newborn larvae into normal rats. It was found that the radioactivity was immediately retained in the lungs and thereafter slowly released, with a mean transit time in excess of 9 hr, as calculated by image analysis. At various times after iv injection of newborn larvae into normal mice, the lungs were removed and parasites were recovered and counted. Fifty to seventy percent of the larvae injected were recovered after 30 sec, between 10 and 30% after 1 min, and less than 4% at 15 min. These results indicate that during the very rapid passage of newborn larvae through the lungs, labeled components of the cuticle are detached and retained. It is suggested that the modifications produced in the cuticle of the newborn larva during its passage through the lung may increase its resistance to the nonspecific defense mechanisms of the host. PMID- 1639156 TI - Plasmodium falciparum: identification and purification of the phosphoglycerate kinase of the malaria parasite. AB - Multiplication of the human malaria parasite Plasmodium falciparum within red blood cells is an energy-dependent process and glucose consumption increases dramatically in infected red blood cells (IRBC) versus normal red blood cells (NRBC). The major pathway for glucose metabolism in P. falciparum IRBC is anaerobic glycolysis. Phosphoglycerate kinase (PGK) is one of the key enzymes of this pathway as it generates ATP. We found that the PGK specific activity in P. falciparum IRBC is seven times higher than that in NRBC. The parasitic origin of the increase in PGK activity is confirmed by isoelectric focusing. Indeed, two P. falciparum isoenzymes with neutral isoelectric points were detected. P. falciparum PGK in purified form has a molecular mass of 48 kDa. Antiserum raised against purified P. falciparum PGK specifically recognizes the 48-kDa protein band in P. falciparum and also reacts with P. berghei and P. yoelii IRBC lysates but does not cross-react with PGK associated with NRBC. PMID- 1639157 TI - Ascaris suum: are trypsin inhibitors involved in species specificity of Ascarid nematodes? AB - Inhibitors of porcine trypsin were prepared from aqueous extracts of the parasitic nematodes Ascaris suum (hogs) and Ascaris lumbricoides (human). In this study three experiments were performed. (1) Polyclonal antibodies were prepared against one isoform of trypsin inhibitor from each parasitic nematode. Each antibody reacted with all isoforms from itself as well as all isoforms from the other parasite. (2) Association equilibrium constants were measured by titrating host trypsins (porcine or human) with the isoforms of trypsin inhibitors from A. suum and A. lumbricoides. While three of the combinations formed tight complexes that can be precipitated, the fourth complex, A. suum trypsin inhibitor-human trypsin has a Ka that is a 300 to 1000 times weaker interaction than the three other titration pairs. (3) Live A. suum worms were incubated in isosmotic media that contained either porcine trypsin or human trypsin. A suum worms survived in porcine trypsin and in the controls but were killed and digested after exposure for 5 days in human trypsin. The first experiment suggests that the trypsin inhibitors from A. suum and A. lumbricoides have similar epitopes, while the second experiment suggests that there are differences near the reactive site of the inhibitors. The consequences of these differences are dramatically demonstrated by the third experiment in which live A. suum worms in the presence of human trypsin die and are digested but those in porcine trypsin survive. These experiments suggest that in order to parasitize a host, a nematode requires a complement of protease inhibitors that interact strongly with those host proteases that are in their environment. PMID- 1639158 TI - Biomphalaria glabrata: influence of calcium, lectins, and plasma factors on in vitro phagocytic behavior of hemocytes of noninfected or Schistosoma mansoni infected snails. AB - In vitro phagocytosis of erythrocytes by hemocytes of B. glabrata, intermediate host of S. mansoni, is strongly influenced by calcium, several lectins, and plasma factors. Our results indicate that two different mechanisms of non-self recognition in B. glabrata may occur: (1) In the presence of calcium, phagocytosis occurs in noninfected and in infected snails without involvement of any other substances, and hemocytes of schistosome resistant as well as those of susceptible snails are able to recognize and phagocytose the target cells. (2) In the absence of calcium, phagocytosis occurs if bridging molecules (heterologous lectins in our assays) were present for which effector and target cells possess binding sites or if target cells were plasma coated prior to the assays. In suspensions in homologous plasma, hemocytes of both snail strains, infected or noninfected, subsequently showed phagocytic activities of about 70-80%. Preincubation of target cells in homologous plasma resulted in similar high phagocytic activities of hemocytes even in the absence of plasma during the standard assay. In these assays, a significantly higher proportion of hemocytes of resistant snails phagocytosed plasma-opsonized erythrocytes, whereas hemocytes of susceptible snails internalized less erythrocytes per cell and needed 60 min to phagocytose at percentages equivalent to that of resistant hemocytes within 10 min. Preincubation of erythrocytes in resistant plasma significantly increased the subsequent phagocytic activity of susceptible hemocytes, whereas preincubation of erythrocytes in susceptible plasma decreased the phagocytosis level of resistant hemocytes. PMID- 1639159 TI - Trypanosoma cruzi: involvement of IgG isotypes in the parasitemia control of mice immunized with parasite exoantigens of isoelectric point 4.5. AB - In a previous work we demonstrated that Trypanosoma cruzi exoantigens of pI 4.5 (Ea 4.5), whose most important epitopes are glucidic, are able to induce a partially protective immune response in mice. To ascertain the involvement of antibody isotypes in this protection, we immunized mice with Ea 4.5 plus Bordetella pertussis as adjuvant. The analysis of immune response by skin test revealed the occurrence of specific immediate type hypersensitivity on Day 15 after the last immunization. By ELISA and using Ea 4.5 as antigen, specific IgG1 antibody was detected. When formaldehyde-fixed epimastigotes were used as antigen, binding of IgG1 and IgG2 was observed. Trypomastigotes incubated for 1 hr at 33 degrees C with the immune sera and then injected in normal syngeneic mice produced a significantly lower parasitemia than trypomastigotes incubated with the control sera. This capacity of anti-Ea 4.5 sera was resistant to 56 degrees C for 2 hr and was diminished after the absorption of immune sera with the carbohydrate moiety of Ea 4.5. The assay with the immune IgG1 and IgG2, separated through protein A-Sepharose affinity chromatography, showed that IgG1 retains most of this capacity. Purified immune IgG1 revealed two antigenic bands of molecular weight between 50 and 55 kDa in SDS-PAGE of Ea 4.5. PMID- 1639160 TI - Brugia pahangi: production of a monoclonal antibody reactive with the surface of infective larvae. AB - Monoclonal antibodies against infective third-stage larvae (L3) of Brugia pahangi were generated from mice immunized with L3 antigens. The monoclonal antibodies were L3 stage-specific or stage-nonspecific. A BpG1 monoclonal antibody (IgG1 subclass) showing L3 stage-specificity was examined in detail. BpG1 recognized the surface of B. pahangi L3 and also reacted with the surface of Brugia malayi L3 but not with the surface of filarial worms of other genera, such as Acanthocheilonema viteae and Litomosoides carinii. BpG1 promoted cellular adhesion to the surface of B. pahangi L3. BpG1 bound on living L3 was shed but the shedding rate was relatively slow. The surface antigen recognized by BpG1 had a molecular weight of 58 kDa. It was stable to heat and periodate treatments but sensitive to trypsin digestion and was released from living L3 by SDS but not by Triton X-100 or CTAB. Preincubation of L3 with BpG1 significantly reduced the recovery rate of worms compared with the preincubation with a monoclonal antibody (IgG1 subclass) against the inner tissues of B. pahangi L3 or control supernatant of P3U1 myeloma cells. This result suggests that the antigen containing the BpG1 epitope may be one of the targets of a protective immune response against Brugia infection. PMID- 1639161 TI - Plasmodium falciparum: induction of biologically active antibodies to gp195 is dependent on the choice of adjuvants. PMID- 1639162 TI - Schistosoma mansoni: silver ion (Ag +) stimulates and reversibly inhibits lipid induced cercarial penetration. AB - Certain long-chain polyunsaturated fatty acids (FA) found on mammalian skin trigger cercariae to penetrate and transform into schistosomules; however, the mechanism by which FAs stimulate cercariae is unknown. In order to determine whether argentophilic papillae concentrated at the apical region of the cercariae are the chemoreceptors that may mediate cercarial response to FAs, an assay assessed the proportion of cercariae that penetrated a 0.25% agar matrix in the presence (61%) and the absence (2.3%) of linolenic acid at 0.22 mM. Silver nitrate (Ag+) which selectively binds to cercarial papillae (Short and Cartrett, J. Parasitol. 59, 1041, 1973) is nontoxic (at 0.09 mM used in this study) as demonstrated by the ability of Ag+ treated cercariae to mature successfully into adult worms (8.8% maturation compared to 10.2% of untreated controls, n = 5) after subcutaneous injection. When Ag+ was added to cercarial suspensions, penetration into linolenic-impregnated agar was significantly inhibited (80.8%). Washing cercariae free of Ag+ reversed this inhibition. These data, as well as observations that both argentophilic papillae and cercarial response to FAs disappeared within 3 to 4 hr after mechanical conversion to schistosomules, implicate argentophilic papillae on cercariae as chemoreceptors for lipid stimulation. PMID- 1639163 TI - Ancylostoma caninum: reduced glutathione stimulates feeding by third-stage infective larvae. AB - The resumption of feeding in vitro has been proposed as an indicator of the reactivation of development by arrested third-stage hookworm larvae. The tripeptide glutathione was tested for its ability to induce in vitro feeding by third-stage infective larvae of the canine hookworm Ancylostoma caninum. Reduced glutathione, but not oxidized glutathione, stimulated larval feeding in a specific, concentration-dependent manner. Feeding began at 5-10 mM, and reached a plateau at 25-50 mM. Incubation in reduced glutathione for 3 hr was sufficient to stimulate the maximum feeding response at 24 hr. Larvae began feeding within 6 hr of incubation with reduced glutathione, and feeding reached a maximum percentage by 24 hr. The reducing agents dithiothreitol and 2-mercaptoethanol failed to stimulate feeding, whereas S-alkyl derivatives of reduced glutathione were stimulatory. Reduced glutathione synergistically increased serum-stimulated feeding to greater than 90% of the sample population, and low concentrations of glutathione appeared to enhance feeding by sensitizing the larvae to a stimulatory component in serum and not by a chemical interaction with a serum component. The data suggest that reduced glutathione might participate in the transition from the free-living third-stage larva to the parasitic third-stage larva during infection. PMID- 1639164 TI - Schistosoma mansoni: single-step purification and characterization of glutathione S-transferase isoenzyme 4. AB - A soluble glutathione S-transferase isoenzyme, designated SmGST-4 was purified to apparent homogeneity in a single step from the cytosol of adult Schistosoma mansoni by selective elution of the enzyme from a glutathione-agarose affinity column using glutathione disulfide. SmGST-4, which comprised about 5% of the bound glutathione S-transferase activity, could be distinguished from the previously characterized glutathione S-transferase isoenzyme family (SmGST 1/2/3), by its unique chromatographic behavior, lower subunit M(r) (26,000), differences in substrate specificity and inhibitor sensitivity, and a lack of reactivity with antiserum to SmGST-3. The purified isoenzyme catalyzed the conjugation of several model xenobiotics including 1-chloro-2,4-dinitrobenzene, ethacrynic acid, and trans-4-phenyl-3-buten-2-one. Like the SmGST-1/2/3 isoenzyme family, SmGST-4 failed to catalyze the conjugation of a model epoxide substrate, 1,2-epoxy-3-(p-nitrophenoxy)propane. Because glutathione S-transferases from other organisms play a role in protecting cells against the toxic products of lipid peroxidation, SmGST-4 and the members of the SmGST-1/2/3 isoenzyme family were tested for their capacity to reduce cumene hydroperoxide and to catalyze the conjugation of 4-hydroxyalk-2-enals. Although all four isoenzymes catalyzed both reactions, the specific activity of SmGST-1, SmGST-2, and SmGST-3 toward cumene hydroperoxide was at least 10-fold greater than that of SmGST-4. In contrast, the latter more effectively conjugated a homologous series of 4-hydroxyalk-2-enal isomers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639165 TI - Toxocara canis: a labile antigenic surface coat overlying the epicuticle of infective larvae. AB - An electron-dense coat covering the surface of Toxocara canis infective-stage larvae is described. This coat readily binds to cationized ferritin and ruthenium red, indicating a net negative charge and mucopolysaccharide content, and can be visualized by immuno-electron microscopy only if cryosectioning is employed. Monoclonal antibodies reactive to the surface of live larvae bind the surface coat but not the underlying cuticle in ultrathin cryosections. The surface coat is dissipated on exposure to ethanol, explaining the lack of surface reactivity of conventionally prepared immunoelectron microscopy sections of T. canis. Differential ethanol extraction of surface-iodinated larvae demonstrates that the major component associated with the coat is TES-120, a 120-kDa glycoprotein previously identified by surface iodination, which is also a dominant secreted product. The surface-labeled TES-70 glycoprotein is linked with a more hydrophobic stratum at the surface, while a prominent 32-kDa glycoprotein, TES 32, is more strongly represented within the cuticle itself. Antibody binding to the coat under physiological conditions results in the loss of the surface coat, but this process is arrested at 4 degrees C. This result gives a physical basis to earlier observations on the shedding of surface-bound antibodies by this parasite. An extracuticular surface coat has been demonstrated on Toxocara larvae prior to hatching from the egg and during all stages of in vitro culture, suggesting that it may play a role both in protecting the parasite on hatching in the gastrointestinal tract and on subsequent tissue invasion in evading host immune responses directed at surface antigens. PMID- 1639166 TI - Schistosoma mansoni: cell-specific expression and secretion of a serine protease during development of cercariae. AB - Eukaryotic serine proteases are an important family of enzymes whose functions include fertilization, tissue degradation by neutrophils, and host invasion by parasites. To avoid damaging the cells or organisms that produced them, serine proteases must be tightly regulated and sequestered. This study elucidates how the parasitic blood fluke Schistosoma mansoni synthesizes, stores, and releases a serine protease during differentiation of its invasive larvae. In situ hybridization with a cDNA probe localized the protease mRNA to acetabular cells, the first morphologically distinguishable parasite cells that differentiate from the embryonic cell masses present in the intermediate host snail. The acetabular cells contained vimentin but not cytokeratins, consistent with a mesenchymal, not epithelial, origin. Antiprotease antibodies, localized by immunoperoxidase, showed that the protease progressively accumulated in these cells and was packaged in vesicles of three morphologic types. Extension of cytoplasmic processes containing protease vesicles formed "ducts" which reached the anterior end of fully differentiated larvae. During invasion of human skin, groups of intact vesicles were released through the acetabular cytoplasmic processes and ruptured within the host tissue. Ruptured protease vesicles were noted adjacent to degraded epidermal cells and dermal-epidermal basement membrane, as well as along the surface of the penetrating larvae themselves. These observations are consistent with the proposed dual role for the enzyme in facilitating invasion of host skin by larvae and helping to release the larval surface glycocalyx during metamorphosis to the next stage of the parasite. PMID- 1639167 TI - Trichinella spiralis: dose dependence and kinetics of the mucosal immune response in mice. AB - The role of the mucosal immune response in helminth infections is not clear. In this study, the dose dependence and kinetics of the mucosal immune response to Trichinella spiralis were determined in experimentally infected Swiss Webster and BALB/c mice. The primary mucosal isotype was sIgA, although IgG was also detected, and primary infections with 10 and 150 larvae produced an anamnestic response on challenge. The mucosal and systemic immunoglobulin responses were dose dependent in both primary and challenge infections. The fecundity and length of worms and the rate of expulsion from the gut were determined on Day 6 postchallenge in Swiss Webster mice. Adult worm recovery and fecundity were reduced by greater than 50% and worm length by 28% in mice infected and challenged with 10 larvae and by 90, 85, and 35%, respectively, in mice infected and challenged with 150 larvae. The rate of expulsion was correlated with the size of both primary and challenge doses and a reduction in fecundity was correlated with the size of the primary dose only. The reduction in worm length did not differ significantly between the infection doses, but the trend was similar to that for expulsion. In BALB/c mice the expulsion response was dissociated from a reduction in fecundity and worm length, the latter two being positively correlated with sIgA levels, supporting a role for sIgA and/or IgG in these effects. However, expulsion does not appear to be dependent on the mucosal immunoglobulin response. PMID- 1639168 TI - Heat shock proteins. Introduction. PMID- 1639170 TI - Mammalian heat shock protein families. Expression and functions. AB - When prokaryotic or eukaryotic cells are submitted to a transient rise in temperature or to other proteotoxic treatments, the synthesis of a set of proteins called the heat shock proteins (hsp) is induced. The structure of these proteins has been highly conserved during evolution. The signal leading to the transcriptional activation of the corresponding genes is the accumulation of denatured and/or aggregated proteins inside the cells after stressful treatment. The expression of a subset of hsp is also induced during early embryogenesis and many differentiation processes. Two different functions have been ascribed to hsp: a molecular chaperone function: chaperones mediate the folding, assembly or translocation across the intracellular membranes of other polypeptides, and a role in protein degradation: some of the essential components of the cytoplasmic ubiquitin-dependent degradative pathway are hsp. These functions of hsp are essential in every living cell. They are required for repairing the damage resulting from stress. PMID- 1639169 TI - Heat shock response in Drosophila. AB - Major alterations in genetic activity have been observed in every organism after exposure to abnormally high temperatures. This phenomenon, called the heat shock response, was discovered in the fruit fly Drosophila. Studies with this organism led to the discovery of the heat shock proteins, whose genes were among the first eukaryotic genes to be cloned. Several of the most important aspects of the regulation of the heat shock response and of the functions of the heat shock proteins have been unraveled in Drosophila. PMID- 1639171 TI - Heat shock proteins and infection: interactions of pathogen and host. AB - Invasive microorganisms encounter defensive attempts of the host to starve, destroy and eliminate the infection. In experimental model systems aiming to imitate defensive actions of the host, microorganisms respond by the rapid acceleration in the rate of expression of heat shock and other stress proteins. Heat shock proteins (hsp) of most if not all pathogens are major immune targets for both B- and T-cells. Host cells involved in the defensive action cannot avoid exposure to their own reactive compounds, such as oxygen radicals, resulting in premature cell death and tissue damage. Long-term consequences to the host may include cancer. In cells in tissue culture, induction of host-specific hsps occurs upon exposure to oxidants and in viral infections. Drugs that bind to members of the hsp70 family induce peroxisome proliferation and hepatocarcinoma, but may open the way for the development of novel drugs in support of antimetabolite treatment of infections and cancer. PMID- 1639172 TI - The humoral immune response to heat shock proteins. AB - Humoral immune reactions to heat shock proteins (hsp) from microorganisms are one aspect of microbial infections in humans. The production of antibodies which are specific to epitopes present on procaryotic hsp leads also to the appearance of cross-reactive serum antibodies in the host organism that react with human hsp. This article discusses the consequences of such autoreactive antibodies for the host in context with the development of immune tolerance and autoimmune diseases, especially rheumatoid arthritis (RA), and in experimental animal models for arthritis such as adjuvant arthritis in rats. On the basis of epitope cross reactivity between hsp and other host proteins, a hypothesis is presented for the development of autoimmune disease following the production of hsp-specific antibodies. PMID- 1639174 TI - Deficiency of fibrinolytic enzyme activities in the serum of patients with Alzheimer-type dementia. AB - Previously we reported that there is a kallikrein deficiency in the cerebral tissue of patients with Alzheimer-type dementia. The present study was performed to investigate protease changes in the serum of these patients. The results showed that the kallikrein activity was normal, but that the activities of plasmin and urokinase were significantly low. The present findings indicate a derangement in the clotting and fibrinolytic systems in Alzheimer patients. PMID- 1639173 TI - Heat shock proteins in autoimmune disease. From causative antigen to specific therapy? AB - Heat shock proteins (hsp) are highly conserved from bacteria to man. Bacterial hsp, with approximate molecular weights of 60 kDa (hsp60), are immunodominant antigens that are immunologically cross-reactive with their mammalian counterparts. Hsp molecules are therefore useful in studies of fundamental questions concerning immune responses to foreign as opposed to self antigens. The finding that immune responses to hsp are associated with both experimentally induced and spontaneous autoimmune diseases in animals has prompted intensive research to assess the role of bacterial hsp as the etiological agents involved in the development of autoimmune diseases. Recent evidence from animal models of autoimmune disease has clearly demonstrated the involvement of hsp in both the pathogenesis and the immunoregulation of autoimmune diseases. Studies with arthritogenic and diabetogenic T cell clones have identified immunogenic epitopes of hsp. These have been shown to ameliorate adjuvant arthritis in Lewis rats, and insulin-dependent diabetes mellitus (IDDM) in non-obese diabetic (NOD) mice. Such studies may have important therapeutic implications for the future treatment of human autoimmune disease. PMID- 1639176 TI - Catecholamine metabolism in the vas deferens and the adrenal gland with special reference to the central catecholamine-depleted state. AB - Experiments were carried out to elucidate the role of central catecholamines in regulating catecholamine metabolism in the vas deferens and adrenal gland of the rat. Rats were injected intracerebroventricularly (i.c.v.) with either vehicle or 6-hydroxydopamine (6-OHDA). Groups of animals pretreated with vehicle or 6-OHDA (i.c.v.) were injected intraperitoneally (i.p.) with alpha-methyl-para-tyrosine (AMT), a tyrosine hydroxylase inhibitor. Catecholamine turnover rates were estimated by determining norepinephrine or epinephrine content after administering AMT. Central norepinephrine and dopamine contents decreased significantly (p less than 0.05) after treatment with 6-OHDA and AMT. The norepinephrine content of the vas deferens of rats pretreated with 6-OHDA was markedly reduced (p less than 0.001) after administration of AMT, whereas that of the vehicle-treated rats remained unchanged. Administration of 6-OHDA had no effect on the norepinephrine or epinephrine content of the adrenal gland. The present results indicate that central monoaminergic neurons have an inhibitory effect on the adrenergic neurons of the vas deferens. In contrast, this inhibitory regulation does not appear to be exerted on the adrenal glands. PMID- 1639175 TI - Reversal of experimental hemorrhagic shock by dimethylphenylpiperazinium (DMPP). AB - In a rat model of hemorrhagic shock which caused the death of all control rats within 30 min, i.v. injection of the ganglion-stimulating drug dimethylphenylpiperazinium (DMPP) caused a dose-dependent reversal of the shock condition--without the need for reinfusion of the shed blood--starting from the dose of 4 ng/kg i.v. Shock reversal was associated with the mobilization of residual blood and improvement in blood flow, particularly at the carotid level. These results could influence our thinking on pathophysiology and first-aid management of shock. PMID- 1639177 TI - Rapid isolation of mitochondrial DNA. Mitochondrial DNA from Drosophila serrata. AB - A simple and rapid method for isolation of high quality mitochondrial DNA (mtDNA) is presented in this report. Using this method, isolation and restriction site maps for 10 enzymes of the mtDNA of Drosophila serrata were established. PMID- 1639178 TI - Age-related differences in the effect of in vivo administration of indomethacin on hemopoietic cell lineages of the spleen and bone marrow of mice. AB - During 21 days of indomethacin treatment, erythroid cells in the spleens of both young adult and older mice, and in the bone marrow of young adult mice, were increased significantly early in treatment, relative to age-matched control organs, and remained high throughout treatment. During drug exposure, the numbers of myeloid cells in young adult bone marrow, but not spleen, were reduced, but in older mice these cells were elevated in both organs. Lymphoid cells in the young adult and older mouse spleens decreased and increased, respectively, during treatment, but were unchanged and decreased, respectively, in the bone marrow of young adult and older mice. Monocyte-macrophage cells in the spleen were elevated but unchanged in the bone marrow of both age groups. During 14 days of indomethacin treatment of young adult mice, the proportions of precursor cells in DNA synthesis of only the splenic erythroid lineage were increased. Thus, the major hemopoietic lineages in both the bone marrow and spleen are affected by exposure to indomethacin in a time-dependent and age-dependent manner. For all lineages studied, those of the bone marrow were least disturbed and/or were first to recover, even during continued drug exposure. PMID- 1639179 TI - Prevention of carbon tetrachloride-induced liver necrosis by the chelator alizarin sodium sulfonate. AB - The administration of the calcium chelator alizarin sodium sulfonate (ASR) (100 mg/kg ip in saline) 30 min before or 6 or 10 hr after CCl4 (1 ml/kg ip as a 20% v/v solution in olive oil) partially prevents the necrogenic effect of the hepatotoxin at 24 hr, but prevention of CCl4 fat accumulation was not observed. Protective action cannot be attributed to potential decreasing effects of ASR on CCl4 levels reaching the liver, on the covalent binding of CCl4-reactive metabolites to cellular components, or on CCl4-induced lipid peroxidation because ASR does not modify these parameters significantly. ASR administration increases GSH levels in livers of both control and CCl4-poisoned animals and decreases the calcium content of intoxicated animals at 24 hr of poisoning. ASR significantly lowers the body temperature of CCl4-treated animals at different times of the intoxication process. Present and previous results from our laboratory on the preventive effects of another very specific calcium chelator, calcion, and several anticalmodulins suggest that the beneficial effects of ASR might be associated with its calcium chelating ability. Other protective effects of ASR, such as lowering body temperature or increasing GSH content in liver, cannot be excluded. PMID- 1639180 TI - A microscopic and ultrastructural evaluation of dibasic esters (DBE) toxicity in rat nasal explants. AB - Dibasic esters (DBE) solvent has been demonstrated to induce a mild degeneration of the olfactory, but not the respiratory epithelium of the rat nasal cavity following a 90-day inhalation exposure. Previous work has demonstrated that acid phosphatase release is a reliable index of DBE-induced cytotoxicity in an in vitro system of rat nasal explants. In the present study, rat nasal explants were examined microscopically and ultrastructurally following incubation in varying concentrations of a representative DBE, dimethyl adipate (DMA). DMA-induced microscopic and ultrastructural changes in rat nasal explants correlated well with biochemical perturbations associated with DBE exposure in a previous study. In both studies, olfactory epithelium was more susceptible to DMA-induced toxicity than respiratory epithelium and DMA-induced nasal toxicity was attenuated by pretreatment with a carboxylesterase inhibitor. The results of this study support the hypothesis that DBE and potentially other inhaled organic esters induce nasal toxicity via a common mechanism, carboxylesterase-mediated production of toxic acid metabolites. It was established that carboxylesterase rich sustentacular cells are the primary target cells for DBE toxicity in rat nasal explants. It was proposed that degeneration of nasal olfactory sensory cells observed in rats following 90-day inhalation exposure to DBE may be secondary to necrosis and loss of sustentacular cells. PMID- 1639181 TI - State and activity of protein kinase C in postischemic reperfused liver. AB - We have studied the activity and the phorbol-binding capacity of protein kinase C (PKC) in subcellular fractions, as well as the relative amount of the enzyme protein in rat livers reperfused after severe nonnecrogenic ischemia. Ischemia causes a significant decrease in PKC phosphotransferase activity in both membranes and cytosol which lasts long after the reestablishment of the blood flow. The phorbol-binding capacity of the membrane fraction shows the same behavior. The amount of PKC protein decreases during ischemia (-25%) but returns to normal after reperfusion more promptly than activity and binding capacity, suggesting that PKC resynthesized in postischemic livers is either functionally defective or incapacitated by unsuitable conditions of the environment. We have also measured the contents of some lipids that may influence PKC activity in the cell. During ischemia and reperfusion there is a significant increase in the content of 1,2-diacylglycerol (DAG), which is the physiological activator of PKC, but under the conditions occurring in the ischemic/postischemic livers DAG apparently cannot bind to the enzyme and fulfill its function. Total phospholipids, phosphatidylcholine, and phosphatidylethanolamine, which significantly decrease at 60 min of ischemia, return to normal levels 1 hr after reperfusion. PMID- 1639182 TI - Interaction of cardiac alpha-actinin and actin in the presence of doxorubicin. AB - The therapeutic use of doxorubicin (an antitumoral antibiotic belonging to the anthracycline group) is limited by its cardiotoxicity. Adriamycin (DXR) causes myocardial subcellular damage, such as myocytolysis, disarray of actin filaments, and alterations in the Z-band with loss of sarcomeric organization. We studied the effect of stoichiometrical concentrations of DXR on the interaction between cardiac actin and alpha-actinin in solution. Doxorubicin inhibits the formation of alpha-actinin/actin tridimensional networks and bundles. The main effect of the drug seems to be on the size of the actin polymers. PMID- 1639183 TI - Autometallographic detection of gold in dorsal root ganglia of rats treated with sodium aurothiomalate. AB - Ultraviolet light autometallography, a very sensitive method for gold detection, was applied to sections of dorsal root ganglia from adult male Wistar rats treated with intraperitoneal injections of sodium aurothiomalate. Silver amplified traces of gold were detected within the cytoplasm of ganglion cells, satellite cells, Schwann cells, macrophages, endothelial cells, and fibroblasts throughout the ganglia. Gold was never detected in axons nor myelin sheaths. In the electron microscope, gold deposits were restricted to the lysosomes irrespective of cell type or dosage. PMID- 1639184 TI - Concepts in protein folding. AB - Certain concepts and misconceptions in the field of protein folding are discussed from the viewpoint of a theoretical physicist. It is argued that there can be no protein folding code and that perceived correlations between sequence or composition and three-dimensional structure are more likely to be an artefact of a limited database than a real result. Attempts at using molecular dynamics algorithms are also likely to produce artefactual results because results depend critically on the unknown hamiltonian energy function. Correct calculations of configurational entropy are thought to be the most likely next step in understanding how and why proteins fold. PMID- 1639185 TI - Recent advances in minisatellite biology. AB - Highly polymorphic tandemly repeated 'minisatellite' loci are very abundant in the human genome, and of considerable utility in human genetic analysis. This review describes the use of an ordered-array Charomid library in the systematic and efficient cloning of these regions, and in the analysis of the relative overlap between the different probes used to screen for hypervariable loci. Recent work on the process of mutation leading to the generation of new-length alleles is also discussed, including the observation that at least some mutations may be due to unequal exchanges. PMID- 1639186 TI - Elucidation of the gene defect in Marfan syndrome. Success by two complementary research strategies. AB - Marfan syndrome, which is characterized by manifestations in the skeletal, ocular and cardiovascular systems, is one of the most common inherited connective-tissue disorders. The independently performed genetic assignment of the Marfan locus and classical biochemical and immunohistochemical analyses complemented each other in the search for the Marfan gene defect and in 1991 the fibrillin gene in chromosome 15 was identified as the Marfan gene. So far, three mutations leading to the Marfan phenotype have been reported in this gene coding for a microfibrillar protein. The available data suggests a wide spectrum of different mutations of fibrillin and although mutations of the fibrillin gene account for the majority of Marfan cases, evidence also exists for locus heterogeneity in a minority of Marfan cases. PMID- 1639187 TI - Apoptosis. Biochemical events and relevance to cancer chemotherapy. AB - Two distinct pathways for cell death exist. Compared to necrotic death, physiological or apoptotic cell death is an active suicidal process that consists of a cascade of well-regulated synthetic events. Participation of specific genes in apoptosis, and its possible molecular regulation, are considered in order to investigate the mechanism of cell death induced by some cancer chemotherapeutic agents. PMID- 1639188 TI - Protein dynamics. An overview on flash-photolysis over broad temperature ranges. AB - Ligand binding kinetics to heme-proteins between 40 and 300 K point to a regulatory role of protein dynamics. A protein-specific susceptibility of the heme-iron reactivity to dynamic fluctuations emerges from the distribution of reaction enthalpies derived from flash-photolysis measurements below ca. 180 K; we quantify it in terms of 'intramolecular viscosity', postulating that narrow low-temperature enthalpy distributions correspond to low internal viscosity and vice versa. The thermal evolution of ligand binding kinetics suggests, with other results, an interplay between high-frequency transitions of the amino acid side chains and low-frequency collective motions as a possible regulatory mechanism of protein dynamics. PMID- 1639189 TI - Amino acid substitutions influencing intracellular protein folding pathways. AB - Though an increasing variety of chaperonins are emerging as important factors in directing polypeptide chain folding off the ribosome, the primary amino acid sequence remains the major determinant of final conformation. The ability to identify cytoplasmic folding intermediates in the formation of the tailspike endorhamnosidase of phage P22 has made it possible to isolate two classes of mutations influencing folding intermediates-temperature-sensitive folding mutations and global suppressors of tsf mutants. These and related amino acid substitutions in eukaryotic proteins are discussed in the context of inclusion body formation and problems in the recovery of correctly folded proteins. PMID- 1639190 TI - The membrane insertion of colicins. AB - Pore-forming toxins, such as colicin A, are water-soluble proteins that insert into lipid bilayers. The water-soluble structure of Colicin A is known at a high resolution and this review describes the kinetic and structural steps involved in its soluble-to-membrane bound transformation. PMID- 1639191 TI - Crystallographic binding studies with triosephosphate isomerases: conformational changes induced by substrate and substrate-analogues. AB - TIM catalyses the interconversion of a triosephosphate aldehyde into a triosephosphate ketone. This is a simple chemical reaction in which only protons are transferred. The crystallographic studies of TIM from chicken, yeast and trypanosome complexed with substrate and substrate analogues are discussed. The substrate binds in a deep pocket. On substrate binding, large conformational changes are induced in three loops. As a result of these conformational changes in the liganded structure, the active site pocket is sealed off from bulk solvent and the sidechain of the catalytic glutamate becomes optimally positioned for catalysis. PMID- 1639192 TI - Multidomain enzymes involved in peptide synthesis. AB - Biosynthesis of peptides in non-ribosomal systems is catalyzed by multifunctional enzymes that employ the thio-template mechanism. Recent studies on the analysis of the primary structure of several peptide synthetases have revealed that they are organized in highly conserved and repeated functional domains. The aligned domains provide the template for peptide synthesis, and their order determines the sequence of the peptide product. PMID- 1639193 TI - Understanding the functions of titin and nebulin. AB - Individual molecules of the giant muscle proteins titin and nebulin span large distances in the sarcomere. Approximately one-third of the titin molecule forms elastic filaments linking the ends of thick filaments to the Z-line. The remainder of the molecule is probably bound to the thick filament where it may regulate assembly of myosin and the other thick filament proteins. This region also contains a sequence similar to catalytic domains in protein kinases. Nebulin appears to be associated with thin filaments and may regulate actin assembly. PMID- 1639194 TI - The modular architecture of vertebrate collagens. AB - Collagens are typical mosaic proteins containing a number of shuffled domains. These domains have been classified by sequence similarity in order to characterize their structural and functional relationships to other proteins. This analysis provides an overview of homologies of collagen domains. It also reveals two new relationships: (i) a module common to type V, IX, XI, and XII collagens was found to be homologous to the heparin binding domain of thrombospondin; (ii) the modular architecture of a human type VII collagen fragment was identified. Its N-terminal globular domain contains fibronectin type III repeats located adjacent to a Von Willebrand factor type A module. The proposed structural similarities point to analogous subfunctions of the respective domains in otherwise distinct proteins. PMID- 1639195 TI - SH3--an abundant protein domain in search of a function. AB - Src-homology 3 is a small protein domain of about 60 amino acid residues. It is probably made of beta-sheets. SH3 is present in a large number of eukaryotic proteins which are involved in signal transduction, cell polarization and membrane-cytoskeleton interactions. Here we review its occurrence and discuss possible functions of this domain. PMID- 1639196 TI - Prokaryotic polyprotein precursors. AB - Polyproteins have been found only recently in prokaryotes. The four known examples of single bacterial genes encoding precursors that are posttranslationally processed into two mature proteins are addressed here with respect to (i) their genomic arrangement, (ii) the sites of proteolytic processing, (iii) the relevant proteases, (iv) their maturation pathway, and (v) the function of the mature proteins. How these polyproteins may have evolved is also discussed. PMID- 1639197 TI - Peptide display on filamentous phage capsids. A new powerful tool to study protein-ligand interaction. AB - Peptides can be displayed on the surface of filamentous bacteriophages by fusion to phage coat proteins. It was recently shown that vast (10(8)) collections of phages, each exposing a variant of the original peptide, can be constructed and utilized as a general source of peptide ligands. By panning these libraries on a target molecule linked to a solid support it is possible to select, out of the hundreds of millions of clones, those few phages that display a peptide that binds the target molecule. Searching these libraries is a powerful tool to be applied in many areas of fundamental and applied biology. PMID- 1639198 TI - Monoclonal antibody engineering in plants. AB - Techniques for plant transformation have been developed to such an extent that a number of foreign genes are currently being introduced into transgenic plants. Tobacco plants that produce monoclonal antibodies are of interest, because in addition to synthesis of two gene products (i.e. the heavy and light chains), the two polypeptides need to be assembled correctly, in order to result in a functional antibody. The studies on a catalytic antibody suggest that this is the case, and that the antibody functions identically to the native murine-derived antibody. The only difference observed was in the glycosylation of the heavy chain. Further transgenic plants are being generated to produce monoclonal antibodies that may be used therapeutically (and are therefore required in large quantities), or to provide disease resistance in plants. In addition, the ability of plants to assemble antibody complexes is being investigated further, to study the possibility of generating secretory IgA, which consists of heavy and light chains as well as two additional polypeptide units. PMID- 1639199 TI - Do unconventional myosins exert functions in dynamics of membrane compartments? AB - Unconventional myosins have now been identified in amoeba as well as in higher eucaryotic cells. Their cellular localization, their ability to bind membrane vesicles and their ability to produce in vitro movement suggest that they can generate forces on the plasma membrane relative to actin filaments as well as on membrane compartments relative to actin. Genetic approaches and biochemical analysis of cells over-producing nonfunctional domains of unconventional myosins have provided direct evidence for a role of unconventional myosins in movement of intracellular vesicles and have allowed us to formulate hypotheses about the possible mechanisms by which unconventional myosins could participate in the intracellular transport of membrane proteins and secretory proteins. PMID- 1639200 TI - Brefeldin A and the endocytic pathway. Possible implications for membrane traffic and sorting. AB - A number of recent observations have suggested that the endocytic and biosynthetic pathways may share fundamentally similar transport mechanisms at the molecular level. Some of the more striking of these suggestions have come from a comparison of the effects of the macrocyclic lactone brefeldin A (BFA) on endosomes and the Golgi complex. BFA is thought to affect Golgi-specific coat proteins that may be involved in maintaining the structural integrity of the organelle and in regulating membrane transport in the secretory pathway. Many of the effects of BFA on the endocytic system, such as the guanine nucleotide and aluminum fluoride (AlF4-)-regulated induction of microtubule-dependent endosomal tubules, are strikingly reminiscent of the action of the drug on the Golgi complex. Therefore, the similar mechanisms of action of the drug on endosomes suggest that organelles of the endocytic pathway may be associated with similar cytoplasmic coats that could regulate endosome function and integrity. PMID- 1639201 TI - Interleukin-8, a chemotactic and inflammatory cytokine. AB - Interleukin-8 (IL-8) belongs to a family of small, structurally related cytokines similar to platelet factor 4. It is produced by phagocytes and mesenchymal cells exposed to inflammatory stimuli (e.g., interleukin-1 or tumor necrosis factor) and activates neutrophils inducing chemotaxis, exocytosis and the respiratory burst. In vivo, IL-8 elicits a massive neutrophil accumulation at the site of injection. Five neutrophil-activating cytokines similar to IL-8 in structure and function have been identified recently. IL-8 and the related cytokines are produced in several tissues upon infection, inflammation, ischemia, trauma etc., and are thought to be the main cause of local neutrophil accumulation. PMID- 1639202 TI - [Arterial hypertension and diabetes mellitus]. PMID- 1639203 TI - [Is angiotensin II a growth factor?]. AB - Angiotensin II is an octapeptide resulting from the enzymatic cascade of the renin-angiotensin system and involved in vasoconstriction and aldosterone secretion. The extensive use of converting enzyme inhibitors recently suggested that angiotensin II may have a specific action on growth of its target tissues. Cellular models confirm that angiotensin II is able to produce in vitro a cellular hypertrophy of many cell types. Nevertheless a controversy was developed on the real possibility for angiotensin II to act on cell division. Some cells, such as adrenocortical cells, present a clear induction of their division by angiotensin II, but contradictory results were obtained on vascular smooth muscle cells. The mechanism by which angiotensin II induces hypertrophy of its target tissues, is largely unknown but may involve a direct action on proto-oncogene synthesis, or an indirect action on growth factor secretion. The nature of the angiotensin II receptor involved in these mechanisms has to be identified. PMID- 1639205 TI - [Hypertension associated with diabetes: inquiry into the attitudes and behaviors of French physicians]. AB - In order to assess the prevalence of arterial hypertension, diabetes mellitus, and of the association of both diseases, and furthermore, to underline the behaviours and feelings of French physicians in front of these combined diseases, a survey has been undertaken by the SOFRES Medical institute and by Laboratoires Hoechst, which involved 304 physicians in private practice and 67 hospital doctors. After face-to-face interviews, each participant had to fill up a questionnaire dealing with his general feelings and attitudes, and then completed 2 case record forms (5 cases for hospital doctors) from their last patients who presented with hypertension and diabetes mellitus. All these informations have allowed us to describe their behaviours. The 304 physicians have been selected with a regional stratification by a random survey quota method that gave a valid sample from the French medical population: 213 general practitioners (GPs), 67 cardiologists, 24 endocrinologists have been involved in the survey. They have been able to observe 149 hypertensive insulin-dependent diabetic patients and 470 hypertensive non insulin-dependent diabetic patients (respectively 24% and 76%). In addition, 67 hospital doctors (32 cardiologists, 17 diabetologists, 18 nephrologists) have been involved and have filled 255 case record forms (120 insulin-dependent and 135 non insulin-dependent diabetic patients). The association between hypertension and diabetes mellitus is very common: 55% out of the diabetic patients treated by GPs presented with hypertension, 20% out of the hypertensive patients presented with diabetes mellitus. The discovery of hypertension is usually followed by the discovery of non insulin-dependent diabetes mellitus. The opposite feature is observed for the insulin-dependent diabetic patients. The majority of the doctors feels that the cardiovascular prognosis of the association is worse than each single disease. The level of blood pressure that is suitable to start an antihypertensive treatment in hypertensive insulin-dependent and non insulin-dependent diabetic patients is generally lower than for non diabetic hypertensive patients, especially for the diabetologists. Concerning antihypertensive treatments, discrepancies have been observed in between feelings and behaviours of physicians. The class of drug that is thought to be used is obviously different from the one which is really used: angiotensin-converting enzyme inhibitors and calcium antagonists, two rather new classes of drugs are popular while classical classes of antihypertensive agents like diuretics and betablockers are still commonly used. Non pharmacological interventions which are useful for both the treatment of hypertension and diabetes mellitus are not commonly recommended by GPs and specialists. PMID- 1639204 TI - [Control of vascular tone by the endothelium: the coupling active vasodilation in the kidney to renin secretion]. AB - The vascular endothelium plays an essential role in regulating the contractility of the adjacent smooth muscle cell through its secretory and metabolic properties. One of these well known properties is the conversion of angiotensin I into angiotensin II. But the endothelium also secretes at least three compounds able to diffuse to the smooth muscle cell and exerting a paracrine action: these are the prostacyclin (PGI2), the endothelium derived relaxing factor (EDRF) and the endothelin 1. The secretion of these different vasoactive compounds by endothelial cells is triggered by mechanical events, such as the shear stress, or by the effect of several humoral factors locally released, for example from platelets. The compound NO (nitric oxide) is produced by the endothelial enzyme NO synthase from its precursor L-arginine, and is responsible for the vasodilatory and antiplatelets properties of EDRF. NO, by activating the soluble guanylate cyclase in the smooth muscle cell, is responsible for the endothelium dependent vasodilatation. We observed in an isolated perfused rat kidney that the compound L-NAME (NG-monomethyl-L-arginine methyl ester), a competitive inhibitor of NO synthase blocking the production of NO, induces renal vasoconstriction and inhibits renin release. This suggests that not only the renal vasoconstriction but also the renal vasodilatation are active processes, permanently regulated by vasoactive compounds such as EDRF. It seems also that EDRF plays an important role in maintaining the secretion of renin. It can be hypothetized that an abnormality in the release or fate of EDRF might perhaps contribute to high blood pressure, by both a direct effect on the vascular tone and an indirect effect on the release of renin, which in turn regulates also the renal and systemic hemodynamics. PMID- 1639206 TI - [Treatment of hypertension in diabetes: threshold of intervention and therapeutic options]. AB - Early screening for hypertension in diabetic patients and for glycoregulation abnormalities in hypertensives is justified by the additive cardiovascular risks when hypertension and diabetes co-exist and by the accelerated development of diabetic nephropathy and retinopathy if hypertension co-exists. In insulin dependent diabetes, hypertension is generally preceded by microalbuminuria, known to be reduced by angiotensin converting enzyme inhibitors. The requirement for nephropathy prevention and the hemodynamic and/or tissular effects of this therapeutic class could justify their use at a blood pressure level less than that conventionally considered hypertensive. This strategy must be confirmed by prospective trials, already underway, evaluating the nephroprotective efficacy of this therapy. In non-insulin-dependent diabetes, hypertension is often present before the diabetes is diagnosed and antihypertensive therapy, especially thiazide diuretics, could play a demasking or favorizing role. The optimal blood pressure level to which these patients at high renal and coronary risk should be lowered still has to be determined. A prospective study, comparing the effects of strict (treated diastolic blood pressure less than 80 mmHg) and less strict (treated diastolic blood pressure between 90 and 100 mmHg) hypertensive control on coronary event prevention in essential hypertension, is in progress and will have important implications for hypertension treatment in diabetics. Appropriate treatment of other risk factors, such as hyperlipidaemia and smoking, contributes to coronary and renal prevention in all diabetic hypertensives. PMID- 1639207 TI - Ovarian follicular atresia as an apoptotic process: a paradigm for programmed cell death in endocrine tissues. PMID- 1639208 TI - 11 beta-hydroxysteroid dehydrogenase and the short-chain alcohol dehydrogenase (SCAD) superfamily. PMID- 1639209 TI - Detection and partial purification of a potent mitogenic factor for human thyroid follicular cells. AB - Normal adult human thyroid follicular cells have an extremely limited proliferative capacity in vitro. No previously studied mitogen, including thyrotropin (TSH) or epidermal growth factor (EGF), has in our hands resulted in a significant improvement over the 3-4% nuclear [3H]thymidine pulse-labelling index (LI) obtainable with 10% fetal calf serum. Here we report the detection in the conditioned medium from a sub-clone of NIH3T3 fibroblasts of a mitogenic activity capable of increasing this response up to 10-fold, to an LI of over 20%, together with an even greater relative stimulation of mitotic activity. Preliminary characterisation has excluded EGF and TGF alpha, and demonstrated that the activity is bound reversibly by heparin-Sepharose, thus pointing to a member of the heparin-binding fibroblast- or hepatocyte-growth factor families. This material should have wide practical application in facilitating primary culture of follicular cells, and may reveal new mechanisms of stromal-epithelial interaction regulating normal and neoplastic thyroid growth in vivo. PMID- 1639210 TI - Identification of a minor Tg mRNA transcript in RNA from normal and goitrous thyroids. AB - Polymerase chain reaction (PCR) amplification of nt 4502 to nt 5184 of the thyroglobulin (Tg) mRNA from several patients, with or without elevated serum thyrotropin (TSH), showed a predominant fragment of the expected size (683 bp) and a minor fragment of 512 bp. The sequence of this minor fragment revealed that 171 bp were missing between position 4567 and 4737. It is highly probable that the deleted sequence corresponds to a complete exon, suggesting an alternative splicing as mechanism for the generation of the minor transcript. PMID- 1639211 TI - Testosterone-induced diminution of two peptides in spleen cells from testosterone immunosuppressed B10 mice. AB - High-performance liquid chromatography (HPLC) is used to detect testosterone (T) sensitive peptides in spleen cells isolated from female C57BL/10 mice immunosuppressed against Plasmodium chabaudi malaria by T treatment. Two peaks with retention times of about 25 min and 34 min, respectively, were identified to be diminished by about 52% and 47%, respectively, in spleen cells from T-treated mice compared to those from untreated mice. Amino acid sequencing revealed that the 24 min peak consisted of the dipeptide Met-Phe and the 34 min peak contained a degradative fragment of the alpha-chain of hemoglobin. Our data suggest that the immunosuppressive T treatment of B10 mice induces a perturbation of erythrophagocytosis in spleens. PMID- 1639212 TI - Effects of tumour necrosis factor-alpha on growth hormone and interleukin 6 mRNA in ovine pituitary cells. AB - The inflammatory cytokines tumour necrosis factor-alpha (TNF alpha), interleukin 1 (IL-1) and interleukin 6 (IL-6) have been demonstrated to influence pituitary hormone synthesis directly and via the hypothalamus. Furthermore, IL-6 is produced by some anterior pituitary cells suggesting a paracrine/autocrine role for this cytokine. We show that TNF alpha induces dispersed ovine pituitary cells to produce increased levels of growth hormone (GH) and IL-6 mRNA and secreted IL 6 in a dose and time dependent manner. TNF alpha at concentrations between 1-1000 U/ml increased GH and IL-6 mRNA, relative to control levels, by 5 h post stimulation. For IL-6, TNF alpha increased specific mRNA at 5 h and 12 h but not 24 h post-stimulation. TNF alpha also induced secreted IL-6 to levels above that spontaneously secreted at all time points from 5 h to 48 h. Levels of common glycoprotein alpha-subunit and follicle stimulating hormone-beta (FSH beta) subunit mRNA were unaffected by TNF alpha. We conclude that TNF alpha can regulate both GH and IL-6 synthesis in dispersed ovine pituitary cells. The implications for paracrine/autocrine control of pituitary hormone synthesis in acute and chronic disease are discussed. PMID- 1639213 TI - Immunohistochemical localization of transforming growth factor-beta 1 and -beta 2 during follicular development in the adult rat ovary. AB - The transforming growth factors-beta (TGF-beta) affect the metabolic activities of each of the cell types in the ovary. In vitro studies using immature rat ovaries have shown the expression of TGF-beta 1 and/or TGF-beta 2 mRNA in thecal/interstitial cells and in granulosa cells (Mulheron and Schomberg, 1990; Mulheron et al., 1991). To obtain information on the localization of TGF-beta 1 and TGF-beta 2 in the rat ovary in vivo, we have examined the immunohistochemical staining using antibodies specific for either TGF-beta 1 or TGF-beta 2. In the adult ovary the immunostaining for TGF-beta 1 was intense, whereas the staining for TGF-beta 2 was faint. The pattern of immunostaining for TGF-beta 1 and TGF beta 2 remained constant in the interstitial cell compartment and was not affected by the stage of the oestrous cycle. Since the interstitium surrounds follicles at all stages of development we conclude that TGF-beta is not actively involved in regulating the progression of follicles at discrete stages. At the time of antrum formation in the follicle, intense staining for TGF-beta 1 was observed in thecal cells. Around the preovulatory stage of development, TGF-beta 1 and TGF-beta 2 immunoreactivity was also found in the granulosa cells. In the corpus luteum, intense staining for TGF-beta 1 was found in some areas, whereas other areas were negative. Weak to moderate staining for TGF-beta 2 was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639214 TI - Expression and characterization of full-length and partial human androgen receptor fusion proteins. Implications for the production and applications of soluble steroid receptors in Escherichia coli. AB - We have expressed fusion proteins encoding defined segments of the coding segment of the human androgen receptor (hAR) in Escherichia coli using the pGEX-2T expression vector. Large quantities of fusion proteins containing glutathione-S transferase (GST) linked to the amino or carboxy terminal region of the receptor and a fusion protein containing the complete amino acid sequence of the androgen receptor were produced in soluble form. The GST hAR fusion proteins containing the hormone-binding domain of the androgen receptor exhibit high affinity specific binding for a variety of natural and synthetic androgens. Analysis of the binding properties of the complete and truncated androgen receptor fusion proteins revealed that the amino terminus affects the Kd of the fusion proteins for mibolerone (0.89 vs. 3.43 nM for the truncated and complete fusion proteins, respectively). Despite these differences, both the truncated and complete hAR fusion proteins exhibit a higher affinity for dihydrotestosterone than for testosterone, implying that the preferential affinity for dihydrotestosterone observed in androgen receptor prepared from native sources is a measure of the inherent structure of the hormone-binding domain. Furthermore, the ligand receptor complex is stable, as the ligand is not easily displaced with unlabelled competitor and is stable to mild heat denaturation. Fusion proteins containing the DNA-binding domain demonstrate specific DNA binding, as evidenced by studies using segments of the mouse mammary tumor virus long terminal repeat (MMTV-LTR) and synthetic glucocorticoid response elements. These studies establish that GST hAR fusion proteins exhibit physical properties similar to those of native androgen receptor. Affinity purification using a glutathione affinity resin and cleavage of the fusion proteins at a thrombin cleavage site permits a marked enrichment using a two-step purification. The use of such methods will facilitate the study of the normal and mutant receptor proteins. PMID- 1639216 TI - Prostaglandin F2 alpha and gonadotropin-releasing hormone increase intracellular free calcium in rat granulosa cells. AB - Changes in cytosolic free calcium concentration ([Ca2+]i) in response to prostaglandin F2 alpha (PGF2 alpha) and gonadotropin-releasing hormone (GnRH) were measured in single rat granulosa cells, using the calcium-sensitive fluorescent dye, fura-2AM. In 90 out of 135 granulosa cells (67%), there was a 3- to 4-fold increase in resting [Ca2+]i within 30 s of administration of PGF2 alpha (10(-6) M). The resting [Ca2+]i returned to pre-stimulation levels in approximately 80 s. Granulosa cells were responsive to PGF2 alpha at concentrations ranging from 10(-7) M to 10(-4) M (n = 7). Within this range of concentrations, the magnitude of the calcium response did not differ. In another series of experiments, the majority (93%, n = 57) of the granulosa cells which responded to PGF2 alpha also responded to GnRH. Neither the magnitude of the [Ca2+]i response nor the time to response differed between PGF2 alpha and GnRH. Furthermore, simultaneous treatment of granulosa cells with both hormones did not generate a larger response than with either hormone alone. During perifusion with low calcium media, the characteristic [Ca2+]i response to PGF2 alpha decreased, and was eliminated within 10 min (n = 9). Similar observations were made in response to GnRH under these conditions. These data confirm that PGF2 alpha and GnRH stimulate a transient increase in [Ca2+]i in rat granulosa cells, the source of which may be shared intracellular stores. PMID- 1639215 TI - Stimulation of DNA synthesis in rat uterine cells by growth factors and uterine extracts. AB - Replicative DNA synthesis, as measured by thymidine incorporation, has been measured in rat uterine cells in primary culture in response to growth factors. Insulin, insulin-like growth factor-I (IGF-I), multiplication-stimulating activity (MSA) and platelet-derived growth factor (PDGF) stimulated DNA synthesis, while estradiol, epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), basic fibroblast growth factor (bFGF) and relaxin did not stimulate or did so weakly and only at very high concentrations. Uterine acid extracts also stimulated DNA synthesis. IGF-I stimulated at concentrations consistent with its acting through the IGF-I receptor; however, insulin stimulated at concentrations higher than expected for its acting through its receptor and this its action may be mediated through the IGF-I receptor. IGF-I was found in uterine tissue by radioimmunoassay (RIA). There was a 5- to 10-fold increase in IGF-I in the uteri from ovariectomized rats that had been treated with estradiol 24 h earlier. This is analogous to the increase in growth factor activity found previously in rat uterus after 24-h estradiol treatment (Beck, C.A. and Garner, C.W. (1989) Mol. Cell. Endocrinol. 63, 93-101). These data are consistent with the hypothesis that estradiol effects in the uterus are in part mediated through IGF-I. PMID- 1639217 TI - Thyroid hormone and androgen regulation of nerve growth factor gene expression in the mouse submandibular gland. AB - The nerve growth factor (NGF) content of the mouse submandibular gland (SMG) is under hormonal control and is modulated by both thyroid hormones (TH) and androgens. The sexual dimorphism of the gland is well documented. In the adult male mouse, the SMG contains 10 times more NGF compared to the female. Conversely, castration of male mice reduces the SMG NGF levels to those found in control females. In order to determine the locus at which androgens and TH exert their effect on NGF gene expression in the SMG, steady-state NGF mRNA levels were determined. Daily treatment of adult female mice with TH for 1 week increased NGF mRNA levels 6-fold. Androgen treatment produced a 20-fold increase in SMG NGF mRNA, which was comparable to levels detected in the control adult male SMG. The effect of TH on NGF mRNA levels was time-dependent and coincided with the increase in NGF protein concentrations. At 48 h after a single TH injection, NGF mRNA levels (measured in SMG total RNA) increased 2-4-fold, while heteronuclear (hn) RNA levels were increased 1.5-2-fold. The NGF gene transcription rate was determined by run-on assay following TH treatment. A small but significant 2-fold induction by TH of NGF gene transcription was found at 24-48 h. Cytoplasmic RNA prepared from the same SMGs used in the run-on experiments was tested by S1 nuclease protection; NGF cytoplasmic RNA was increased 7-fold in the SMGs of females treated with TH 48 h previously. These results demonstrate that the effect of TH on NGF gene expression is due in part to an induction of NGF gene transcription. The discrepancies observed between transcription rate and mRNA levels suggest that the major effect of TH is at the post-transcriptional level, possibly mRNA stabilization. The time required to observe an induction of TH on NGF gene transcription is suggestive of an indirect effect, possibly through the induction by TH of another protein which in turn activates the NGF gene. PMID- 1639218 TI - Protein synthesis and insulin regulation of p33 and PEPCK gene expression. AB - Insulin stimulates transcription and cytoplasmic accumulation of a specific mRNA (termed p33), while inhibiting transcription and accumulation of phosphoenolpyruvate carboxykinase (PEPCK) mRNA in rat H4IIE (H4) hepatoma cells. The present work examines the role of protein synthesis in regulation of these genes by insulin and dexamethasone. Like insulin, cycloheximide and anisomycin, two protein synthesis inhibitors, induced p33 transcription and reduced PEPCK transcription. The combination of either protein synthesis inhibitor and insulin did not induce p33 transcription or inhibit PEPCK transcription beyond that observed with either protein synthesis inhibitor alone. Dexamethasone induced both p33 and PEPCK transcription. The combination of insulin and dexamethasone, or protein synthesis inhibitors and dexamethasone, abolished dexamethasone induced PEPCK transcription. Thus, protein synthesis inhibitors regulate transcription of the p33 and the PEPCK genes in an insulin-like manner. PMID- 1639219 TI - Importance of the carboxyl terminus of human thyroid peroxidase in the efficient expression of the protein in eukaryotic cells. AB - Carboxyl terminal truncation of membrane-associated human thyroid peroxidase (hTPO), with the elimination of its single membrane-spanning and short intracytoplasmic regions, generates a soluble, secreted, enzymatically active protein (amino acids 1-848). In order to determine the effects of further carboxyl terminal deletions on the expression of hTPO, Chinese hamster ovary cells were stably transfected with plasmids constructed to express amino acids 1 771, 1-636, 1-539 and 1-382 of the 933 amino acid TPO protein, respectively. Unlike hTPO1-848, the more severely truncated TPO mutant proteins could not be detected in conditioned media by polyclonal anti-TPO antibodies. Using detergent solubilized microsomal proteins from these cells, very low levels of hTPO1-771 (approximately 90 kDa), but not the more extensive deletion mutations, were detected by these anti-TPO antibodies. Confirmation of the loss of efficient expression of more severely truncated hTPO was obtained using a anti-hTPO monoclonal antibody with an epitope near the amino terminus and which recognizes only the denatured protein. The mRNA for all hTPO mutants was detected in the stably-transfected Chinese hamster ovary cells. In summary, the present study indicates that a largely intact extracellular portion of hTPO is required for expression in eukaryotic cells. PMID- 1639220 TI - Defective inhibition of gastrin release by antral distension in duodenal ulcer patients. AB - The gastrin response to a low and a high dose of gastrin-releasing peptide infusion was studied in healthy volunteers and in patients with duodenal ulcer disease. In duodenal ulcer patients, the gastrin response was exaggerated. Cholinergic blockade did not change the gastrin release in healthy volunteers. Antrum distension during neutralization of the gastric lumen was unable to stimulate gastrin release, also under cholinergic blockade. However, in healthy volunteers distension of the antrum significantly inhibited the gastrin response to gastrin-releasing peptide infusion. This inhibitory influence was most pronounced in patients given the lower dose of the neuropeptide. Cholinergic blockade counteracted the inhibitory effect exerted by antral distension. On the other hand, antral distension did not alter the gastrin response to gastrin releasing peptide in patients with duodenal ulcer disease. These results suggest an additional defective inhibitory mechanism in duodenal ulcer patients. PMID- 1639221 TI - Regulation of cholesterol metabolism and low-density lipoprotein binding in human intestinal Caco-2 cells. AB - In the present paper, the regulation of 3-hydroxy-3-methylglutarylcoenzyme A (HMG CoA) reductase, acylcoenzyme A cholesterol acyltransferase (ACAT) and low-density lipoprotein (LDL) binding was studied in the human colon cancer carcinoma cell line Caco-2. LDL down-regulated HMG-CoA reductase activity in a dose-dependent fashion to a minimum of 28% of control at 200 micrograms/ml and LDL binding to 52% of control. The activity of ACAT was stimulated by LDL. High-density lipoprotein 3 (HDL3) increased HMG-CoA reductase activity, whereas cholesteryl ester formation was slightly decreased. Inhibition of the endogenous cholesterol biosynthesis by mevinolin increased both LDL binding and activity of HMG-CoA reductase. This effect was reversed by the addition of mevalonolactone but not by LDL. It is concluded that regulation of HMG-CoA reductase and LDL binding is subject to the availability of non-sterol products of mevalonic acid and of exogenous cholesterol. ACAT is regulated mainly by the level of its substrate cholesterol. PMID- 1639222 TI - Soluble interleukin-2 receptor, interleukin-6 and interleukin-1 beta in patients with Crohn's disease and ulcerative colitis: preoperative levels and postoperative changes of serum concentrations. AB - Crohn's disease (CD) and ulcerative colitis (UC) show an intestinal activation of T cells and macrophages within the inflamed lesions. The aim of the present prospective study was to determine whether circulating interleukins (IL) represent useful markers of immune activation in vivo and to characterize their respective roles in monitoring disease activity. Serum concentrations of the soluble IL-2 receptor (sIL-2R), IL-6 and IL-1 beta were measured in 10 patients with CD and 10 patients with UC before, at day 10 and 2 years after resection of inflamed bowel segments. The data were correlated with neopterin, C-reactive protein and other standard parameters of disease activity. Preoperatively, mean sIL-2R concentration was 495 +/- 62 U/ml (mean +/- SEM; healthy controls; 210 +/- 25 U/ml; p less than 0.02) in CD and 705 +/- 120 U/ml (p less than 0.00002) in UC. The corresponding IL-6 serum concentrations were 37 +/- 6 U/ml in CD (controls: 11 +/- 0.6 U/ml; p less than 0.0036) and 33 +/- 6 U/ml (p less than 0.04) in UC. Two years postoperatively, sIL-2R was still elevated in 6 out of 9 patients in both disease groups. These patients did not differ from the remaining group with respect to disease activity. Serum IL-6, elevated in 7 patients with CD and in 6 patients with UC at day 10 postoperatively, had returned to normal in all patients by this time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639223 TI - Recurrent gastrointestinal bleeding due to angiodysplasias in the small bowel. Experience with panendoscopic diagnosis and treatment in 6 patients. AB - Detection of bleeding from angiodysplasias located in the small bowel remains a diagnostic challenge. Intraoperative panendoscopy of the small bowel is a safe method with high diagnostic yield. The experience with this technique in 6 patients with overt bleeding or melena is described. During the panendoscopy a suture technique was used as therapeutic modality. This method is easy, cheap, does not require special skills or instruments, and the result is seen immediately. PMID- 1639225 TI - The identification of genes specifically expressed in epithelial cells of the rat intestinal crypts. AB - Undifferentiated embryonic and dedifferentiated tumor cells express genes that are down-regulated or not expressed in differentiated tissue. The progenitor cells of the intestinal crypt are undifferentiated cells that, similarly, should express genes that are not evident in the more differentiated villus cells. Some of these genes may be related to the control of differentiation. We attempted to define crypt-associated genes by constructing a cDNA library from isolated rat intestinal crypt cells and screening for messages that remained after subtractive hybridization using greater than 20-fold more mRNA from villus than from the crypt cells. This process identified about two percent of the colonies containing transcripts expressed by the crypt cell. Northern blot analysis showed hybridization to messages in a range from 700 to 12,000 base pairs. Six clones out of 136 initial isolates were shown to hybridize to crypt mRNAs at levels four to tenfold greater than to villus mRNAs. Three of these clones showed greater hybridization to mRNA of the distal (ileum) when compared to the proximal end of the adult small bowel. Increased expression in fetal rat intestine was seen for five mRNAs and in fetal liver for four mRNAs when compared to adult. Most of the crypt associated gene probes preferentially bound mRNA from ovary, kidney, and spleen but did not bind mRNA derived from testis, muscle and brain. Cultured mouse teratocarcinoma cells (F9) showed high levels of three of these transcripts. Portions of each insert were sequenced and examined for homology to entries in national computer banks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639224 TI - Genomic potential of erythroid and leukocytic cells of Rana pipiens analyzed by nuclear transfer into diplotene and maturing oocytes. AB - In order to determine whether differentiated somatic cells maintain genetic totipotency, nuclear transplantations from several differentiated somatic cell types into eggs and oocytes were performed previously in Rana pipiens and Xenopus laevis. The formation of postneurula embryos and tadpoles under the direction of the test nuclei demonstrated their genetic multipotency. In addition, Rana erythrocyte nuclei transplanted to oocytes directed more extensive tadpole development than those injected into eggs. We have extended our studies of the genomic potential of differentiated somatic nuclei from the peripheral blood of Rana pipiens. First, we show that the developmental potential of erythrocyte nuclei injected into oocytes at first meiotic metaphase was greater than those injected into diplotene oocytes. Second, we demonstrate that erythroblast and leukocyte nuclei transplanted to oocytes at first meiotic metaphase promoted more advanced tadpole development than those previously injected into Xenopus eggs. Third, erythrocyte nuclei were more successful in promoting advanced tadpole development compared with erythroblast and leukocyte nuclei. The results show that differentiated somatic nuclei transferred to the cytoplasm of oocytes at first meiotic metaphase display enhanced genomic and developmental potential over those transplanted to diplotene oocytes and eggs, at least for the three nuclear cell types tested from the peripheral blood. PMID- 1639226 TI - Organization of non-muscle myosin during early murine embryonic differentiation. AB - A monoclonal antibody (3D10) recognizing myosin heavy chain was isolated following immunization with a synthetic peptide sequence of eight amino acids. The antibody reacted with purified rabbit skeletal myosin and light mero-myosin in enzyme-linked immunosorbent assays and Western immunoblotting. A band of approximately 200 kDa was detected in cell extracts of an embryonal carcinoma (EC) cell line (P19EC) and one of its cloned differentiated derivatives, suggesting reactivity against non-muscle myosin. By indirect immunofluorescence, typical myosin banding patterns were observed in cryostat sections of human skeletal and cardiac muscle tissue. In undifferentiated P19EC cells, speckled immunofluorescent staining was observed in the cytoplasm that became organized in cortical rings where the cells made direct contact with each other. These rings consisted of circular bundles of F-actin decorated by myosin. Undifferentiated embryonic stem (ES) cells derived directly from mouse embryos shared the same features, although the pattern was less pronounced. Human testicular primary germ cell tumours showed cortical staining in the embryonal carcinoma component reminiscent of the staining of EC cells in vitro while cytoplasmic staining was observed in tumour cells with a differentiated morphology. In preimplantation embryos, the immunofluorescent staining was observed at cell apices of blastomeres of morula stage embryos. In blastocysts, staining of inner cell mass cells was not detectable. By contrast, various differentiated derivatives of P19EC contained extensive F-actin microfilament bundles throughout the cytoplasm decorated with myosin. Thick stress fibers in filopodious extensions of cells were particularly highly decorated by myosin. Over the nucleus, linear arrays of myosin containing speckled patterns of immunofluorescence were observed that were not associated with F-actin. The same pattern of staining could be observed in trophectoderm cells of the blastocyst. We conclude that embryonic non-muscle myosin is organized in specific patterns depending on the state of differentiation. As the myosin is primarily associated with F-actin we suspect that it forms part of a contractile apparatus that may have significance during embryonic development. PMID- 1639227 TI - In vivo effects of indomethacin--II. Antioxidant enzymes in metal-deficient rats. AB - 1. The in vivo effects of indomethacin on the activity of antioxidant enzymes in erythrocytes, liver and small intestinal mucosa of rats fed a metal-deficient diet were studied. 2. Metal deficiency led to a significant decrease in the activity of the enzymes studied. 3. Neither with the "ulcerogenic" nor with the "therapeutic" dose of indomethacin significant alterations in the enzyme activity were observed. 4. The oral treatment of metal-deficient rats with a copper complex of indomethacin caused a significant increase in the activity of the enzymes studied. 5. The results suggest the participation of indomethacin in the regulation and redistribution of metals in the organism, which is probably effected through in vivo chelation of endogenous metals. PMID- 1639229 TI - Brain and adrenal monoamines and neuropeptide Y in codeine tolerant rats. AB - 1. Monoamine turnover and neuropeptide Y (NPY) levels were investigated in the central and peripheral nervous systems in adult male rats chronically treated with codeine. 2. An increase in the dopaminergic turnover was observed in the striatum and cortex. The norepinephrine levels and the serotoninergic turnover were unchanged in all the brain areas. 3. Epinephrine levels were decreased in the adrenal glands. 4. In addition, we observed a significant decrease of NPY levels in the hypothalamus, the striatum and the adrenal glands. These observed changes were not found when assessing NPY level in plasma fluid. 5. The implication of these modifications in the induction of codeine dependence are discussed in view of previous results obtained with morphine. PMID- 1639228 TI - Plasma concentration of paracetamol and its major metabolites after p.o. dosing with paracetamol or concurrent administration of paracetamol and its N-acetyl-DL methionine ester in mice. AB - 1. Single doses of paracetamol 400 (PAR 400) and 800 mg/kg (PAR 800), SUR 2647 combination (free paracetamol + paracetamol-N-acetyl-DL-methionate, paracetamol/methionine ratio 2:1) equivalent to PAR 400 (SURc 400) and PAR 800 (SURc 800) were given p.o. to male Bom:NMRI mice. 2. The objective was to compare the plasma concentrations of free paracetamol and the major metabolites paracetamol-sulphate and paracetamol-glucuronide for a 6 hr period after each test drug. 3. There was no significant difference between PAR 400 and SURc 400 with respect to plasma paracetamol, paracetamol-glucuronide and paracetamol sulphate concentration with the exception of lower plasma paracetamol concentration (P less than 0.03) at 3 hr following PAR 400. 4. There was no significant difference between PAR 800 and SURc 800 with respect to plasma paracetamol, paracetamol-glucuronide and paracetamol-sulphate concentrations with the exception of lower plasma paracetamol-glucuronide concentration (P less than 0.03) at 4 hr after dosing following SURc 800. 5. Combining free paracetamol and its methionine ester does not seem to alter the pattern of plasma paracetamol, paracetamol-glucuronide and paracetamol-sulphate compared to equal doses of free paracetamol alone after p.o. administration of toxic doses to male Bom:NMRI mice. PMID- 1639230 TI - Comparative pharmacological profile of muscarinic agonists in the isolated ileum, the pithed rat, and the mouse charcoal meal transit test. AB - 1. Several reportedly selective (McN-A-343, M1; RS-86, M2; pilocarpine, M3) and non-selective (oxotremorine, acetylcholine, cis-dioxalone, arecoline, muscarine) muscarinic agonists were examined for comparative pharmacological potency in three diverse models: the guinea pig ileum, the pithed rat, and the mouse charcoal meal transit test. 2. In the guinea pig ileum, all of the compounds examined were associated with concentration-dependent contractions. 3. The apparent order of potency in the isolated ileum was cis-dioxalone greater than acetylcholine greater than oxotremorine greater than arecoline greater than RS-86 greater than pilocarpine greater than McN-A-343. 4. The pA2 values for atropine and pirenzepine in the ileum ranged from 8.4 to 9.4 and 6.1 to 7.7, respectively, indicative of a single receptor, most likely M3. 5. In the mouse charcoal meal transit test, non-selective muscarinic agonists produced dose-dependent increases in gastrointestinal transit, while selective agonists failed to produce any significant changes. 6. Scopolamine methylbromide, a peripherally acting non selective muscarinic antagonist, significantly reduced the ability of muscarine to increase transit. 7. The compounds were further examined for dose-dependent pressor effects in the pithed rat, which are known to be mediated by stimulation of M1-receptors in sympathetic ganglia. 8. McN-A-343 produced the greatest pressor response, as measured by the percent increase in mean pressure, followed by pilocarpine. 9. Pirenzepine antagonized the pressor response of McN-A-343 and pilocarpine in a dose-dependent manner. PMID- 1639231 TI - Antiulcer activity of the calcium antagonist propyl-methylenedioxyindene--V. Localization of site of action. AB - 1. Propyl-methylenedioxyindene (pr-MDI) is an intracellular calcium antagonist which inhibits cold-restraint stress ulceration at subcardiovascular doses (less than or equal to 30 mg/kg). It also inhibits gastric acid secretion evoked by RX77368 (a stable analog of thyrotropin-releasing hormone, the putative mediator of cold-restraint stress ulcers). 2. The objective of this investigation was to localize the site of the inhibitory effect of pr-MDI on gastric acid secretion stimulated by intracisternal (i.c.) administration of RX77368 (100 ng) in rats. 3. Peripheral administration of pr-MDI (30 mg/kg i.p. or i.v.) inhibited the elevated basal and the RX 77368-induced acid secretion in conscious 2-hr pylorus ligated rats. This effect was completely blocked in anesthetized (urethane or pentobarbital) acute gastric fistula rats. 4. Intracisternal administration of pr MDI (0.1-1 mumol) produced a dose-related inhibition of acid secretion in conscious pylorus-ligated rats. However, urethane anesthesia completely blocked the inhibitory effect of i.c.-administered pr-MDI (1 mumol) on RX77368-induced acid secretion. 5. Since previous studies indicate that anesthesia does not inhibit peripheral actions of pr-MDI (e.g. the antiarrhythmic effect), the convergent evidence suggests that the inhibitory effect of pr-MDI on gastric acid secretion is mediated primarily via the central nervous system. PMID- 1639233 TI - Ca-blocking action of stereoisomers of CI-951, (+)-CI-951 (NC-1500) and (-)-CI 951 in the isolated muscle preparations. AB - 1. Stereoselectivity of CI-951 in Ca-entry blocking activity was tested in guinea pig taenia caecum and urinary bladder and rabbit thoracic aorta and basilar artery. 2. NC-1500 ((+)-CI-951) and (-)-CI-951 had a selectivity to the basilar artery. 3. NC-1500 ((+)-CI-951) was about 6-16 times as potent as (-)-CI-951. 4. These results suggest that NC-1500 ((+)-CI-951) may be considered a cerebral vasodilator and have potential usefulness as a therapeutic drug. PMID- 1639232 TI - Ebrotidine effect on the proteolytic and lipolytic activities of Helicobacter pylori. AB - 1. The effect of ebrotidine, a new antiulcer agent, on the activity of mucus degrading of protease and lipase enzymes elaborated by Helicobacter pylori was investigated. 2. In the absence of ebrotidine, the H. pylori protease caused extensive degradation of gastric mucus protein, while free fatty acids, glycerol mono-oleate and lysophosphatidylcholine were produced by the action of H. pylori lipase and phospholipase A enzymes. 3. Introduction of ebrotidine to the incubation system led to the reduction in the rate of mucus protein and lipid degradation. The rate of proteolysis inhibition was proportional to ebrotidine concentration up to 35 micrograms/ml at which point, a 57% reduction in mucus degradation was obtained, while the maximum inhibition of phospholipase A (96%) and lipase (93%) activities occurred at ebrotidine concentration of 60 micrograms/ml. 4. The results indicate that ebrotidine is capable of counteracting the mucolytic activity of H. pylori towards protein and lipid constituents of gastric mucus layer. PMID- 1639234 TI - Haloperidol differentiates smooth muscle contractions induced by release of intracellularly stored Ca and by influx of extracellular Ca. AB - 1. The effects of haloperidol on smooth muscle contraction induced by carbachol, histamine, high K or caffeine in the presence or absence of extracellular Ca were investigated. 2. In the presence of extracellular Ca, the maximal contraction induced by carbachol was reduced by haloperidol, while that by histamine or high K was much less affected. 3. In Ca-free solution, contraction induced by histamine was extremely reduced by haloperidol, while that by carbachol was not affected. 4. These results suggest that haloperidol selectively inhibited signal transduction processes from activation of muscarinic acetylcholine receptors to influx of extracellular Ca and from activation of histamine H1-receptors to release of intracellularly stored Ca. 5. Caffeine-induced contraction in Ca-free solution was markedly potentiated by haloperidol, although haloperidol did not elicit contraction in Ca-free solution by itself. 6. These results suggest that haloperidol increased the sensitivity of Ca-induced Ca release channels to caffeine. PMID- 1639235 TI - Effect of hypolipidemic drugs on cholinesterase activity in the rat. AB - 1. The effect of four hypolipidemic agents with different mechanisms of action (fenofibrate, probucol, colestipol and nicotinic acid) on plasma and liver cholinesterase has been studied. 2. Liver weight and liver weight/body weight ratio increased only after treatment with fenofibrate. 3. Plasma and liver cholinesterase activity increased markedly after fenofibrate, a strong peroxisome proliferator, and slightly after nicotinic acid, a weak peroxisome proliferator. 4. The data obtained suggest that increased cholinesterase activity is due to increased rate of fatty acid oxidation caused by peroxisome proliferators. PMID- 1639236 TI - The effect of physostigmine on the haemorrhagic hypovolemia in anaesthetized rabbits. AB - 1. The effects of physostigmine (70 micrograms kg-1, intravenously) on mean arterial blood pressure, blood volume and survival were studied in anaesthetized rabbits subjected to haemorrhagic hypovolemia. 2. It was found that physostigmine increased the mean arterial blood pressure, increased the residual blood volume, decreased the haematocrit values and increased the survival of the animals. 3. The increase of blood pressure might be due to a general adrenergic activation produced by physostigmine, whereas the increase in plasma volume might be due to changes in pre- to postcapillary resistance ratio. 4. The beneficial effect of physostigmine might also be due to antagonism of humoral factors known to aggravate the hypovolemia (e.g. endogenous opioids). PMID- 1639237 TI - Involvement of GABAergic mechanisms in chloroquine-induced seizures in mice. AB - 1. The influence of some GABAergic agents on tonic seizures elicited by chloroquine was investigated in mice. 2. Chloroquine (45-100 mg/kg) elicited seizures in mice in a dose related manner. 3. Muscimol (1-2 mg/kg), DABA (8-16 mg/kg) and baclofen (4-16 mg/kg) profoundly delayed the onset of chloroquine (65 mg/kg)-induced seizures. The incidence of the seizures was also significantly reduced by muscimol (1-2 mg/kg), DABA (8 mg/kg) and baclofen (4-8 mg/kg). 4. AOAA (10 mg/kg) profoundly reduced the proportion of mice that convulsed while AOAA (20 mg/kg) completely protected mice against chloroquine (65 mg/kg)-induced seizures. 5. Bicuculline (5 mg/kg) and picrotoxin (0.5-1 mg/kg) significantly potentiated chloroquine (50 mg/kg)-induced seizures. The onset of seizures and the number of mice that convulsed were shortened and increased respectively. The onset of chloroquine (65 mg/kg)-elicited seizures was also profoundly shortened. Bicuculline (5 mg/kg) and picrotoxin (0.5 mg/kg) effectively antagonised the protective effects of muscimol (2 mg/kg), AOAA (10 mg/kg) and DABA (8 mg/kg) against chloroquine (65 mg/kg)-elicited seizures. 6. Diazepam (1 mg/kg) and phenobarbitone (20 mg/kg) significantly antagonised chloroquine (65 mg/kg) seizures. The onset of seizures was significantly delayed by both diazepam (0.25 1 mg/kg) and phenobarbitone (10-20 mg/kg). 7. These data suggest that enhancement and inhibition of GABAergic neurotransmission respectively attenuate and potentiate chloroquine seizures in mice. PMID- 1639238 TI - Nicotinylalanine increases cerebral kynurenic acid content and has anticonvulsant activity. AB - 1. Nicotinylalanine is an analogue of kynurenine which has been reported to inhibit the enzymes kynurenine hydroxylase and kynureninase. 2. In the present study rats were given a tryptophan load together with nicotinylalanine two hours before killing, and the brain, liver and kidneys analysed by HPLC for their kynurenic acid content. 3. Tryptophan alone produced a significant elevation of kynurenate but with the additional administration of nicotinylalanine, levels rose dramatically, including a 19-fold increase in brain. 4. In mice the same dose of nicotinylalanine reduced the incidence of seizures induced by leptazol or electroshock treatment. 5. Since kynurenic acid is an antagonist at excitatory amino acid receptors the results may herald a new approach to producing a pharmacological blockade of amino acid receptors in the brain. PMID- 1639239 TI - Changes in GABAergic function after chronic chemical stress. AB - 1. The function of the gamma-aminobutyric acid (GABA)-ergic system in certain areas of the rat brain was investigated after chronic chemical stress (exposure to either vapours 30 sec/day for 20 days). 2. GABA concentration, [3h] -GABA uptake and the activity of the synthesis enzyme glutamate decarboxylase (GAD) were measured. 3. Chronic stress: (a) reduced neuronal uptake of [3H] -GABA in the frontal cerebral cortex (43%) and increased non-neuronal uptake of [3H] -GABA in the hypothalamus (62%); (b) enhanced the activity of GAD (under subsaturating substrate concentration) in the frontal cortex (91%) and in the corpus striatum (69%); (c) did not modify GABA endogenous concentration; (d) did not affect the animals' body weight increase or produce any signs of toxicity. 4. The stimulation of GAD and reduction of [3H] -GABA neuronal uptake in the frontal cortex might suggest the stimulation of GABAergic neurotransmission induced by chronic stress in this area of the rat brain. Together with previous findings the frontal cortex would appear to be a key area in chronic stress processing. PMID- 1639240 TI - Isolation of proteoglycans synthesized by rat heart: evidence for the presence of several distinct forms. AB - 1. The proteoglycans (Ps) synthesized by auricle and ventricle from adult rat heart were studied. 2. Auricle tissue incorporated over two times radioactive sulfate compared to ventricle tissue and the Ps were mainly found in the detergent insoluble fraction. 3. The Ps from both tissues were isolated by ion exchange chromatography on DEAE-Sephacel, followed by gel filtration on Sepharose CL-6B and SDS-PAGE electrophoresis. 4. Enzymatic and chemical degradation of these Ps suggest that at least three and probably four different species of Ps can be observed in heart tissue. 4. A high molecular weight chondroitin sulfate P, a high molecular weight heparan sulfate-P, a chondroitin/dermatan sulfate-P of 240-200 kDa and a dermatan sulfate of 115 kDa. 5. This latter P was specifically immunoprecipitated using rat decorin antiserum. PMID- 1639241 TI - Mechanisms involved in the cardiovascular responses to opioid products of proenkephalin in the anaesthetised rat. AB - 1. Cardiovascular effects of opioid peptide products of proenkephalin, [Met] enkephalin (ME), [Leu] enkephalin (LE), [Met] enkephalyl Arg6-Phe7 (MEAP) and [Met] enkephalyl Arg6-Gly7-Leu8 (MEAGL) have been studied in urethane anaesthetised rats. 2. ME, LE, MEAP and MEAGL produced vasodepression and bradycardia mediated by mu-opioid receptors. 3. Atypical responses to MEAP were observed in a quarter of the animals studied showing tachycardia and pressor effects. This response was probably due to the release of the dipeptide Arg-Phe which exerted its effects at sympathetic ganglia. 4. Studies with the peptidase inhibitors captopril and bestatin showed a differential potentiation of the cardiovascular effects of the proenkephalin products by inhibition of angiotensin converting enzyme and aminopeptidase. 5. The effects of vagotomy, pithing and studies with atropine, and N-methyl levallorphan were used to demonstrate that, for all four proenkephalin peptides, cardiovascular effects were mediated by peripheral opioid receptors and transmission to the CNS via vagal afferents. PMID- 1639242 TI - Triflusal vs aspirin on the inhibition of human platelet and vascular cyclooxygenase. AB - 1. Triflusal is a salicylic derivative that inhibits platelet aggregation in human whole blood with a minimal inhibition of prostacyclin production. 2. Aspirin inhibits platelet aggregation at concentrations that reduce vascular prostacyclin production. PMID- 1639243 TI - Genetic markers associated with high density lipoprotein cholesterol levels in a biracial population sample. AB - An explanation for the consistently documented finding of higher levels of high density lipoprotein-cholesterol in black men relative to white men was sought by comparing the frequency of restriction fragment length polymorphism markers present in blacks and in whites at the gene loci coding for the two major apolipoprotein constituents of high density lipoprotein, apolipoproteins AI and AII. The measurements were made in population-based samples of 45 to 54-year-old black (n = 190) and white (n = 370) subjects from the Minnesota Heart Survey for whom lipoprotein levels were available. The mean high density lipoprotein cholesterol level for black men in the sample (47 +/- 1.5 mg/dl) was higher (P less than 0.05) than that for white men (42 +/- 0.9 mg/dl), while levels in women were not different between races. While the SacI and MspI markers at the apolipoprotein AI-CIII-AIV gene locus showed similar frequencies in blacks compared to whites, the degree of the linkage disequilibrium previously noted between these markers in white subjects was altered in blacks and the minor allele of the PstI marker at this locus was virtually absent in the black subjects (P less than 0.005 vs whites). For black men, there were significant associations of the M2 allele and the S2M2 haplotype at the apolipoprotein AI locus with lower high density lipoprotein-cholesterol levels. The results are consistent with the hypothesis that DNA sequence variations in the vicinity of the apolipoprotein AI-CIII-AIV gene locus are associated with the difference in high density lipoprotein-cholesterol levels between blacks and whites. PMID- 1639244 TI - Linkage studies of schizophrenia: a stimulation study of statistical power. AB - In planning for a linkage study, it is important to determine the number of pedigrees needed to show linkage. Our study overcomes some of the limitations of previous power studies by simulating multigeneration pedigrees to be compatible with the demographic and genetic epidemiological features of schizophrenia; these are variable age at onset, reduced fertility, and increased mortality after onset. We evaluate the power of these pedigrees by first simulating an ascertainment rule requiring at least three ill family members per pedigree and then simulating the trait and marker genotypes according to a single gene model known to fit epidemiological family study data. Our analysis allows for incomplete and age-dependent penetrance, phenocopies, and interpedigree heterogeneity. We present the power to detect linkage at several lod score thresholds since the multiple tests and phenotypic models required for complex diseases may necessitate using a lod score significance level greater than three. The sample size needed to achieve sufficient power is feasible if 50% of the pedigrees are linked to the marker under test. It may not be feasible to detect linkage if only 25% of the pedigrees are linked, even if a very closely linked marker is used. Our results indicate that to be certain of adequate statistical power, linkage analyses of schizophrenia will require very large samples that do not have a marked degree of genetic heterogeneity. PMID- 1639246 TI - Extended pedigree patterned covariance matrix mixed models for quantitative phenotype analysis. AB - Overt computational constraints in the formation of mixed models for the analysis of large extended-pedigree quantitative trait data which allow one to reliably characterize and partition sources of variation resulting from a variety sources have proven difficult to overcome. The present paper suggests that by combining a restricted patterned covariance matrix approach to modeling and partitioning the variation arising from polygenic and environmental forces with an Elston-Stewart like algorithmic approach to modeling variation resulting from a single genetic locus with large phenotypic effects one can produce a model that is at once intuitively appealing, efficient computationally, and reliable numerically. Extensions and variations of this approach are also discussed, as are some simulation and timing studies carried out in an effort to validate the accuracy and computational efficiency of the proposed methodology. PMID- 1639245 TI - An analytical method for assessing patterns of familial aggregation in case control studies. AB - This paper describes an analytical method that is used to assess patterns of disease aggregation within family based on family history information collected in case-control studies. In such a study, cases and controls are thought of as probands whose relatives are identified, and relatives' phenotypes and other covariates such as age, sex, and genealogical relationship with the probands are recorded. By modeling the dependence of relatives' phenotypes on case-control status and other covariates, this method yields adjusted odds ratios that quantify familial aggregation. The estimated standard errors are obtained for statistical inference since the method acknowledges the potential correlations between relatives' phenotypes by using the estimating equations technique. In population-based case-control studies, the estimates and statistical inferences are generalizable to the general population. To illustrate this method, we analyzed a case-control study of colorectal cancer involving 5,190 relatives of 792 cases and 4,478 relatives of 680 population-based controls conducted in Hawaii. Although detailed results will be presented elsewhere, the colorectal cancer was found to aggregate within family with an odds ratio of 2.74 (95% confidence interval (CI): 1.78-4.21). Among parents, the odds ratio for familial aggregation was 2.38 (95% CI: 1.25-4.54). The corresponding value for siblings was 3.09 (95% CI: 1.87-5.11). It was also found that the odds ratio increases from about 2.00 for relatives of the probands who were 50 years or older to 7.66 and 12.84 for relatives of the probands who were between 40 and 50 years and under 40 years, respectively, suggesting that the familial aggregation of colorectal cancer decreases as probands' age increases. PMID- 1639247 TI - Using multidimensional scaling on data from pairs of relatives to explore the dimensionality of categorical multifactorial traits. AB - An accurate specification of the dimensionality and ordering of categorical multifactorial phenotypes (e.g., smoking status, including heavy, moderate, light, and nonsmokers) is an important prerequisite for the genetic analysis of these traits. Typically, phenotypic dimensionality and ordering are determined by comparing the relative fits of alternative parametric threshold models. Here, a method of analysis is described which addresses the same issue of trait dimensionality but does not require parametric assumptions. Specifically, we detail how nonmetric multi-dimensional scaling (MDS), applied to contingency tables which cross-classify the phenotypes or responses of one relative with another, may be used to explore trait dimensionality. Scaling results from deterministic simulation studies indicate that the latent structure of categorical phenotypes can be recovered with nonmetric MDS. Results from stochastic simulations, however, indicate that the accuracy of recovery, as well as the rejection of models of incorrect dimensionality, are strongly dependent upon sample size and the latent liability correlation between relatives. As an application of the method, the dimensionality of a measure of smoking status in 1,656 pairs of monozygotic twins ascertained through the American Association of Retired Persons is considered. The MDS results indicate that the onset of the smoking habit and the quantity smoked in this aging population represent a unidimensional process. The implication this finding has for subsequent genetic analysis is discussed. PMID- 1639248 TI - [Preparation of monosomal lines containing individual human 15, 21, and X chromosomes]. AB - Sorting of human--mouse or human--hamster hybrid cells with particular human chromosomes was performed by in situ hybridization. Total human genomic DNA was heavily labelled with. H and hybridized to metaphase spreads from hybrid clone cells. The method allowed us to not only identify human chromosomes in hybrid cells but also to detect terminal translocations and insertions from 1-2 bands in length to large ones. Biochemical markers of some human chromosomes were analysed using electrophoretic technique in the clones selected. Cytogenetic analysis (G staining) of these clones was made to visualize human chromosomes. Total 99 initial hybrid human--hamster and 26 human--mouse clones were obtained. 53 clones were analysed by in situ hybridization, only one of them being monochromosomal; the latter contained human X chromosome on the background of Chinese hamster chromosomes. Two other monochromosomal clones containing particular 15 and 21 chromosomes, respectively, were obtained by more complicated way from human- mouse hybrid clones using back selection, repeated hybridization and passing through a number of subsequent subclonings. PMID- 1639249 TI - [Genetic differentiation between breeds of horses by polymorphic blood protein loci]. AB - The estimation of genetic differentiation between 27 horses breeds originated in USSR, based on serum proteins polymorphism (loci Tf, Al, Es) is shown. Genetical variability among aborigine breeds is higher then among cultural ones. The erosion of gene pool of Przewalski's Horse is explained by special history of this population and a few horses in analyzing group. Genetic distances reflect the directions and intensity of breeding. High genetical distances between Przewalski's Horse, Shetland Pony and other horses obtained could be explained by overcoming the "bottle neck" of selections in breeding process. Results of investigation shown that 9 aborigine breeds of USSR are clustered in a special group, differed from foreign horse breeds, because their gene pool was quite unique. PMID- 1639250 TI - [Study of interlocus interactions using a series of gene markers in samples from groups with different health status]. AB - Interloci equilibrium between pairs of gene markers in the samples of different health rate in the population of Buryats of Chitinskaya Province was tested. The following methods were used: calculation of interloci correlation coefficients, chi 2-testing of the hypothesis of interloci equilibrium and the modification of principal components analysis on the basis of the matrix of Pearson's coefficients of contingency. In the groups of "extreme" health rate the tendency to increase in interloci disequilibrium was discovered. The reason for this effect is the increase in some phenotype combination frequencies that can be considered as markers of non-specific individual resistance in the environmental condition of the populations studied. PMID- 1639251 TI - [An ecogenetic approach to studying the adaptation and human health]. AB - Genetic markers--blood groups ABO, RH, MN; serum proteins HP, PI, TF, C3; erythrocyte enzymes ACP1, ESD, AK1, PGM1, GLO1, PGD, PGP; and the other: PTC tasting, ear wax types and color vision, were studied in two aboriginal Buryatian populations of Baikal Lake region: in Chitinskaya and Irkutskaya Provinces. Two samples were further divided into subgroups, according to their health status: "healthy", "indefinite" and "sick" by means of special regression procedure. The "healthy" subgroup of the Chitinskaya Province population is characterized by higher frequencies of PTC-tasters: 0.871 vs. 0.757 in the "sick" part (chi 2 = 5.36, p less than 0.05); higher frequency of the phenotype PI M1M1: 0.734 in "healthy" vs. 0.547 in "sick" (chi 2 = 8.89, p less than 0.01); also, lower frequency of the PI M1M2 phenotype: 0.148 and 0.299, respectively (chi 2 = 7.49, p less than 0.01); the frequencies of the phenotype TF C2C2 are: 0.015 and 0.076 (chi 2 = 5.48, p less than 0.05). In Irkutskaya Province population differences between "healthy" and "sick" subgroups were discovered for blood group AB: "healthy" 0.046 and "sick"--0.175 (chi 2 = 11.28, p less than 0.010); for GC (1F 2)--0.214 and 0.116 (chi 2 = 4.45, p less than 0.05). Some other differences between "healthy" and "sick" in both populations are not significant. Some trends concerning heterozygosity in loci--GC, PGM, TF were discovered. The results are considered from the viewpoint of higher fitness of some genetic traits in the populations studied. PMID- 1639252 TI - [Frequency of non-disjunction and loss of sex chromosomes in oogenesis in the Drosophila melanogaster mutant I(1) ts 403 with a defect in the heat-shock protein system in anoxia and at high temperature]. AB - A unique property of Drosophila melanogaster l(1)ts403 strain with the defect in heat shock protein system (HSP) is high frequency of losses and non-disjunction of sex chromosomes induced by heat shock (HS) (37 degrees C, 1 h). This effect was shown in only 6-14-th stages of oocytes. Anoxia was not effective in induction of these mutations. Successive action of anoxia and HS decreased loss frequency and non-disjunction in comparison with the only action of HS. These findings agree with the data in literature indicating that HSP synthesis was increased in the l(1)ts403 mutant when first anoxia and then HS were administered, in contrast to the action of HS only. The role of HSP in the recovery of HS-induced disruptions (chromosomal proteins and meiotic division apparatus) which can lead to chromosome non-disjunction and losses is discussed. PMID- 1639253 TI - [Properties of super unstable mutations in the Drosophila melanogaster yellow locus]. AB - The properties of super-unstable systems of the white, singed and ocetilless loci obtained as a result of P-M dysgenesis induction in the strains with a mobilized Stalker were described earlier. In the studies of super-instability in ocetilless locus, six super-unstable mutations in the yellow locus were obtained. Detailed genetic analysis was performed resulting in isolation of 80 alleles with different phenotype expression. In general, super-instability in the yellow locus reminds that in the white and ocetilless loci. Most of alleles are highly unstable possessing a characteristic pattern of mutation changes. Also, sub systems were found in the yellow super-unstable system. Each consists of several mutually inter-converting alleles which possess a characteristic phenotype, mode and rate of mutation changes. PMID- 1639254 TI - [PHO2 and GCN4 transcription activators in the regulation of Saccharomyces cerevisiae acid phosphatase synthesis]. AB - The possibility of substitution of the PHO2 activator protein by GCN4 protein in transcriptional regulation of acid phosphatase genes PHO5 and PHO11 was demonstrated in the yeast Saccharomyces cerevisiae. We observed the increase in acid phosphatase synthesis in the case of gcn4-delta 1 pho2-delta 1 mutant transformed with YCp88 (GCN4-wt) plasmid in comparison with that in nontransformed cells. The mode of repression of acid phosphatase synthesis in two types of transformants gcn4-delta 1 pho2-delta 1 (GCN4-wt) and gcn4-delta 1 pho2 delta 1 (PHO2-wt) was studied. It wat demonstrated that repression of acid phosphatase synthesis in the first type of transformants took place at lower concentration of Pi than was necessary for the second type of transformants. The model of interactions between the GCN4 activator protein and PHO regulatory factors is proposed. PMID- 1639255 TI - [Structure and evolution of the D17LeH80-like locus in the murine t-complex]. AB - The t complex in the proximal part of chromosome 17 is one of the most thoroughly studied regions of the mouse genome. We determined the sequence of Tu80, a molecular clone derived from microdissected fragments of chromosome 17. The sequence data demonstrated that the total length being 324 bp, Tu80 contains an open-reading frame (ORF) of 204 bp. Two fragments were detected within the ORF, one homologous to the LINE1-element, the other to the first intron of the C epsilon gene of mouse immunoglobin. A sequence designated NOV1 was isolated from the genomic library of mouse chromosome 17. NOV1 was found to contain a B2 insert, making in structurally different from Tu80. The sequences of Tu80 and NOV1 were compared with those of LINE1 and the first intron of the C epsilon gene. The results suggested that the ancestor of the Tu80-like sequence might have arisen through illegitimate recombination between the fragments of LINE1 and the C epsilon gene. It is concluded that Tu80 and NOV1 might have resulted from duplication of the ancestral sequence and following divergence. The comparative analysis also demonstrated high degree of conservation of the LINE1 fragments in Tu80 and NOV1, as well as in the LINE1 in a number of mammalian species. Based on the structure of human, rat, rabbit and mouse LINE1 fragments, and also on that of NOV1 and Tu80, phylogenetic tree has been constructed. Its topology is consistent with the accepted phylogenetic relationships among the species studied. The data available tend to support the assumption that the ancestor for the Tu80-like sequence might have arisen not later than 27-33 million years ago. PMID- 1639256 TI - [Mathematical modeling of the dynamics of frequency of the mutation process. I. Age features of SA frequency dynamics tendency]. AB - A mathematical method for modelling SA frequency dynamics tendencies, depending on age, for different fixation moments and in general for the whole interval of observation is suggested. The criteria of remainder dispersion attitude is used for choosing an optimal model. The initial hypothesis about discrepancies distribution law is used for checking adequateness of the optimal model to the research process. In addition, aposteriory trust intervals are built for the initial and forecast SA frequency values and the hit into them corresponding the experimental values of SA frequencies is controlled. An example of practical realization of the model proposed is considered and the results obtained analysed. PMID- 1639257 TI - [Suppressor mutation, interacting with the white alleles of Drosophila melanogaster]. AB - A system of genetic instability was developed by crosses of males y2 wa4 with females C(1)DX, ywf. Mutations occurred in the second and third generations with the rate 0.7.10(-3)-1.5.10(-3). A novel gene named Suppressor of wa4--Su(wa4) was selected in this system. The Su(wa4)M1 is dominant and was localised in the position of 309 map units. Su(wa4)M1 suppressed wa, wa4, wbf, waG which had insertions of different transposable elements in different introns of the white locus. However, Su(wa4) does not interact with other w mutations. So, we suggested that Su(wa4) is trans-regulatory gene and its product involves in the expression regulation the white locus, probably, on the transcriptional level. PMID- 1639258 TI - [Polymerase chain reaction with universal primers for studying genomes]. AB - Universal primer ability of generating conservative and variable UP-PCR (universally primed polymerase chain reaction) species-specific patterns was analysed on bacteria to serve as an example. Also, two important properties of the UP-PCR patterns (species/primer DNA hybridization specificity) are characterized. PMID- 1639259 TI - [Bacillus subtilis gene rec223: molecular cloning and proposed function of its protein product]. AB - Chromosomal DNA fragment which complemented rec223 mutation of Bacillus subtilis was cloned. Introduction of one copy of the cloned gene into the cells of the rec mutant restored both normal activity for DNA damages repair after mitomycin C action and recombination proficiency. Using multicopy vector led to no formation of recombinants, which was probably connected with overproduction of rec223 gene protein product in Bacillus subtilis cells. PMID- 1639260 TI - [Isolation and characteristics of new mutants of Saccharomyces cerevisiae with increased spontaneous mutability]. AB - To isolate some new genes controlling the process of spontaneous mutagenesis, a collection of 16 yeast strains with enhanced rate of spontaneous canavanine resistant mutations was obtained. Genetical analysis allowed to define that the mutator phenotype of these strains is due to a single nuclear mutation. Such mutations were called hsm (high spontaneous mutagenesis). Recombinational test showed that 5 mutants under study carried 5 nonallelic mutations. It was revealed that the mutation hsm3-1 is a nonspecific mutator elevating the rate of both spontaneous canavanine resistant mutations and the frequency of reversions in mutations lys1-1 and his1-7. Genetical analysis revealed that mutation hsm3-1 is recessive. The study of cross sensitivity of mutator strains to physical and chemical mutagens demonstrated that 12 of 16 hsm mutants were resistant to the lethal action of UV, gamma rays and methylmethanesulfonate, and 4 mutants were only sensitive to these factors. Possible nature of hsm mutations is discussed. PMID- 1639262 TI - [Participation of the HIM1 gene from Saccharomyces cerevisiae in correction of heteroduplex DNA. Molecular cloning of the gene]. AB - A group of Saccharomyces cerevisiae mutants deficient in repair of induced premutation lesions (him mutants) were previously isolated in our laboratory. Recessive him1 mutant had enhanced level of spontaneous and induced mutagenesis as well as specific altered mitotic conversion. This HIM1 gene was supposed to be involved in the process of mismatch correction of heteroduplexes. In this paper the correction efficiency of in vitro constructed heteroduplex DNA in wild-type cells and him1 mutant was studied. In the former cells heteroduplex DNA was repaired highly efficiently (about 90%), this repair efficiency being reduced in him cells approx. two times as compared with the wild-type cells. Molecular cloning of yeast chromosomal DNA fragments containing HIM1 gene was carried out. The clones were selected from the bank of yeast DNA fragments by complementing him1-1 mutation which enhances conversion frequency in ADE2 gene. One of the DNA fragments was analysed by restriction endonuclease digestion and shown to contain an insert of 6 Kb. Chromosomal integrants were obtained by homologous recombination between the plasmid and chromosomal gene him1. PMID- 1639261 TI - [Cloning and regulation of the expression of the lysA gene from Bacillus subtilis]. AB - Cloning of Bacillus subtilis DNA fragment with the lysA gene encoding diaminopimelatecarboxylase (EC 4.1.1.20) was done. The cloned gene in poorly expressed both in Escherichia coli and in Bacillus subtilis. Some DNA sequence distant from the lysA gene seems to be necessary for full gene expression, this sequence having been not cloned together with the lysA. The sequence in needed for regulation of the expression as well. PMID- 1639263 TI - [Isolation and analysis of protease-deficient mutants of Bacillus amyloliquefaciens]. AB - Four types of protease negative mutants of Bacillus amyloliquefaciens A50 were selected after four stages of step-by-step UV light mutagenesis. EDTA, and PMSF were used as inhibitors of protease activity to characterize the protease negative mutants with regard to the protease type. The electrophoretic patterns of proteases from culture medium of B. amyloliquefaciens protease deficient mutants were studied. The proinsulin stability in the culture medium of different mutants was analysed. Protease deficient B. amyloliquefaciens strain A50-32 may be used as a recipient for cloning and expression of a foreign proteins genes. PMID- 1639264 TI - [Gene-enzyme system of alcohol dehydrogenase and adaptation of Drosophila to increased temperature]. AB - Properties and allelic ADH (alcohol dehydrogenase) control in Drosophila melanogaster were studied upon flies' cultivation under conditions of hypotherm of different intensity and duration. Lines homozygotic for F allele (vg) and S allele (cn) of the Adh gene as well as genetically enriched experimental cn' and vg' populations containing a small number of AdhF/AdhS heterozygotes at the initial stage were used. It was found out that physiological adaptation of the species to momentary influence of elevated temperature is accompanied by modification of physical properties of ADH-F according to ADH-S. Constant influence (during the life span of 25 generations) of elevated temperature on the population changes its genetic structure, due to selective advantages of the S allele of Adh under these conditions. PMID- 1639265 TI - Vectors for plant transformation and cosmid libraries. AB - A series of vectors has been constructed for the purpose of introducing cloned DNAs into plant genomes, using Agrobacterium tumefaciens-mediated transformation methods. One of these vectors, pCIT20, is a plasmid that contains a multiple cloning site (MCS), and a marker (Hph) that confers hygromycin resistance to plant cells. The others are all cosmid vectors which allow insertion of up to 46 kb of plant genomic DNA, and which also contain all of the necessary sequences for A. tumefaciens-mediated plant transformation. The cosmid vectors either contain a Hph marker (pCIT30), or a kanamycin-resistance marker (pCIT101-104). Three of the cosmid vectors (pCIT30, pCIT101, and pCIT103) carry bacteriophage T7 and SP6 promoters flanking the cloning Bg/II site, for synthesis of end-specific RNAs. The end-specific RNAs may be used as probes when labeled with radioactive or biotinylated nucleotides, for example, in a chromosome-walking experiment. The other two cosmid vectors (pCIT102 and pCIT104) carry restriction sites flanking the insertion site (XhoI) for convenient release of the insert by restriction digests. These sites, in combination with sites internal to the insert, allow the generation of end fragments for subcloning or labeling probes. These vectors should be valuable for isolation and analysis of plant genes, using transformation, library screening, and chromosome-walking approaches. PMID- 1639266 TI - Ribozymes designed to inhibit transformation of NIH3T3 cells by the activated c Ha-ras gene. AB - We have designed hammerhead ribozymes that cleave c-Ha-ras mRNA mutated at codon 12 (GGU----GUU). Plasmids containing the ribozyme-encoding genes were expressed under the control of the long terminal repeats of Rous sarcoma virus in NIH3T3 cells transfected with the activated c-Ha-ras gene. These ribozymes were found to inhibit formation of foci (by about 50%) by cleaving the oncogene mRNA, rather than by hybridizing to it. Furthermore, when the activated c-Ha-ras gene was cotransfected with the ribozyme-encoding gene, three morphologically flat colonies were found and isolated. We also found that expression of c-Ha-ras was suppressed in cells containing ribozymes. PMID- 1639267 TI - Structure and myofiber-specific expression of the rat muscle regulatory gene MRF4. AB - We have cloned an 11.3-kb rat genomic DNA fragment encompassing the muscle regulatory factor 4 (MRF4) protein-coding sequence, 8.5 kb of 5'-flanking sequence, and 1.0 kb of 3'-flanking sequence. In order to study MRF4 gene expression, the rat myogenic cell line, L6J1-C, which expresses the endogenous MRF4 gene only in differentiated myofibers, was transfected stably with the full length genomic clone and various 5' deletions. RNase protection assays demonstrated that MRF4 genes containing as little as 430 bp of 5'-flanking sequence exhibited an increase in expression as the cells differentiated into myofibers, indicating that elements responsible for fiber-specific expression are contained within this cloned DNA fragment. Similar up-regulation was observed with genes containing 1.5 kb of 5'-flanking sequence. Interestingly, MRF4 genes containing 5.0 kb and 8.5 kb of 5'-flanking sequence were up-regulated to even higher levels, suggesting that additional myofiber-specific regulatory elements located between 1.5 and 5.0 kb upstream from the coding region play a role in regulating the expression of this muscle-specific gene. PMID- 1639268 TI - Differential regulation of TIMP-1 and TIMP-2 mRNA expression in normal and Ha-ras transformed murine fibroblasts. AB - A cDNA containing the complete coding region of the murine tissue inhibitor of metalloproteinases-2 (TIMP-2) was isolated using reverse transcription-polymerase chain reaction amplification. The predicted murine TIMP-2 amino acid sequence shows 96% identity with human TIMP-2, but only 42% identity with murine TIMP-1. This high degree of evolutionary conservation between the human and mouse proteins suggests that TIMP-2 performs an essential biological function. The expression of the TIMP-1 and TIMP-2 mRNAs was examined in normal and ras transformed murine fibroblasts. While TIMP-1 transcription was highly serum inducible in normal murine C3H10T1/2 fibroblasts, TIMP-2 mRNA expression was largely constitutive. A series of ras-transformed derivatives of C3H10T1/2 fibroblasts showed great variability in TIMP-1 expression: some lines retained serum inducibility, others displayed constitutive expression at either high or low levels. In contrast, TIMP-2 expression was insensitive to transformation. Neither TIMP-1 nor TIMP-2 expression at the RNA level, or total TIMP activity in conditioned media could be correlated with the metastatic potential of the ras transformed lines. Our data demonstrate that the mechanisms that regulate murine TIMP-1 and TIMP-2 expression are distinct arguing for different physiological roles for the two TIMPs. PMID- 1639269 TI - Production of v-Myb and c-Myb in insect cells infected with recombinant baculoviruses. AB - Recombinant baculoviruses expressing the v-myb and c-myb genes in infected insect cells were constructed. The electrophoretic mobilities of their immunoreactive products were the same as those of the authentic Myb proteins from chicken cells. The system provides a convenient source of relatively large amounts of v-Myb or c Myb for in vitro binding studies. PMID- 1639271 TI - Structure of the murine gene encoding apolipoprotein A-I. AB - A 1.6-kb DNA fragment containing the gene encoding apolipoprotein A-I from the mouse, Mus musculus, has been cloned and sequenced. It contains three exons separated by two introns and encodes a secreted polypeptide of 262 amino acids (aa), 238 of which constitute the mature protein. Comparisons with the rat and human proteins indicate moderate levels of shared identity (71 and 66%, respectively), although the overall aa compositions yield proteins with identical pIs (5.4). Kyte-Doolittle analyses of the three proteins indicate that there is no significant difference in the structure of these apolipoproteins. PMID- 1639270 TI - Cloning and characterization of a highly conserved satellite DNA from the mollusc Mytilus edulis. AB - Sperm DNA of the common mussel, Mytilus edulis, has been found to contain a highly repeated sequence identifiable upon restriction with the endonuclease ApaI. The repetitive nucleotide (nt) sequence amounts to 0.63% of the mollusc genome with an estimated copy number of 5.4 x 10(4) copies per haploid complement. The monomer unit with a 173-bp repeat length has been cloned. Progressive DNA digestions with ApaI yield ladder-like banding patterns on agarose gels, indicating that the repeated elements are tandemly arranged in the genome and therefore represent a sequence of satellite DNA. The degree of internal redundancy of the reiterated sequence is deemed negligible, since nt sequence analysis of a random set of cloned monomers has detected the presence of only a few direct repeats while inverted repeated motifs or any other internal substructures appear absent. The homologies found among cloned monomers are strikingly high, averaging 95%. The results suggest that the exceptional sequence homogeneity of this satellite DNA may be attributed either to some homogenizing mechanism or to evolutionary conserved trends. PMID- 1639272 TI - Tissue-specific and hormonally regulated expression of the puromycin N acetyltransferase-encoding gene under control of the rabbit uteroglobin promoter in transgenic mice. AB - Transgenic mice bearing two fragments of the rabbit uteroglobin 5'-flanking region fused to the new reporter gene (pac) encoding puromycin N acetyltransferase (PAC) showed a different pattern of expression. Transgenic lines (C0.4) harboring a 404-bp fragment (-396/+8) had a uterus-specific expression slightly inducible by estrogen, lacking detectable expression in other tissues where the uteroglobin-encoding gene is naturally expressed in rabbit. Transgenic lines (C3.2) bearing a longer fragment of 3.2-kb (-3254/+8) showed hormonally regulated expression in the uterus and the male genital tract, and detectable expression in the lung. In addition, the nonstimulated uterine expression of the transgene was higher in C0.4 lines than in C3.2 lines. It could be concluded that all sequences required for uterus-specific expression should be present within the 404-bp fragment, and that other upstream (-396) sequences are responsible for expression in the lung and male genital tract, as well as for a possible down modulation of expression in the uterus. PMID- 1639273 TI - Synthesis of a gene encoding bovine substance P precursors and its expression in Escherichia coli. AB - Using an efficient Escherichia coli expression system, we have been able to obtain the precursor of substance P, alpha-preprotachykinin (alpha PPT). The alpha PPT protein is produced in E. coli as a fusion to beta-galactosidase, and accumulates in the cytoplasm as insoluble inclusion bodies. We also produced protachykinin (alpha PT), i.e., alpha PPT without a signal peptide. Further purification and characterization of the alpha PPT and alpha PT polypeptides strongly suggest that fully purified products can be obtained using our procedures. PMID- 1639274 TI - Production of human serum transferrin in Escherichia coli. AB - Transferrin (Tf) crystals diffract to only medium resolution. The mediocre quality of the crystals may be due to two factors: (1) the genetic variations naturally present in the primary sequence of Tf, and (2) the glycosylation of the protein. To control genetic variations and glycosylation of samples of Tf, it would be desirable to express the Tf gene from a recombinant clone. Additionally, expression of Tf from a clone would allow for manipulation of the structure of Tf. The cDNA encoding Tf has been cloned into the pL-based expression vector, pRE1, and the T7-based expression vectors, pRSETA and pET11A. The Tf expression plasmids, pTF-SSn and pTF-ESn, based on the T7 expression vectors, efficiently produce a 76-kDa protein that is approximately the same size as deglycosylated Tf, cross reacts with anti-Tf antibodies, and matches the deduced N-terminal amino acid sequence. Expression of Tf in Escherichia coli will allow the production of genetically pure, unglycosylated protein. PMID- 1639275 TI - Polymorphism at codon 72 of the p53 gene in human acute myelogenous leukemia. AB - A common polymorphism at codon 72 of the p53 gene in patients with acute myelogenous leukemia (AML) was analyzed by single-strand conformation polymorphism assay and sodium dodecyl sulfate polyacrylamide-gel electrophoresis of immunoprecipitated 35S-labeled P53 protein. No association between this polymorphism and a marked predisposition to AML was found. The half-lives of these two polymorphic forms of P53 were equivalent in normal phytohemagglutinin stimulated lymphocytes, while the P53 Pro72 isoform was found to be twice as stable as the Arg72 isoform in Daudi cells. PMID- 1639276 TI - A rat beta-interferon-induced mRNA: sequence characterization. AB - Polymerase chain reaction amplification of a cDNA derived from rat aortic smooth muscle cells, using sequences from conserved regions of the intramembrane domains of adrenergic receptors as primers, yielded the clone, rat8. This clone possesses a high degree of sequence similarity to a series of human interferon (IFN) inducible genes. The rat8 sequence is 70% similar to that derived from the human alpha-IFN-induced gene, 9-27; there is 66% similarity between the deduced amino acid sequences encoded by the rat and the human genes. The rat homologue hybridizes with many bands in Southern analysis of rat DNA, suggesting that it is a member of a large multigene family. PMID- 1639277 TI - The application of eight reported temperature-based algorithms to calculate the postmortem interval. AB - There exist numerous temperature-based techniques to calculate the early postmortem interval of human corpses. This paper presents eight commonly used time of death algorithms and describes how they were applied to eight corpses. PMID- 1639278 TI - Remote control skull positioning device for superimposition studies. AB - The success of the superimposition technique requires positioning the skull in the same posture of the face as seen in the given photograph. A scientific method for positioning the skull has already been proposed by Sekharan. This paper deals with the simple remote control tilt and rotatory device developed in the Forensic Sciences Department, Madras. A pan and tilt arrangement usually utilized in surveillance cameras and two a.c. servomotors, one to tilt the pan and the other to rotate the pan are used. PMID- 1639279 TI - Sex diagnosis of Chinese skulls using multiple stepwise discriminant function analysis. AB - Sixty Chinese skulls (30 males and 30 females) from Liaoning Province of the People's Republic of China were used in this study. Forty-one variables on each skull were measured and one group of 14 and a second group of 5 variables were selected from all the variables by applying multiple stepwise regression on a computer. Discriminant equations for the 14 and 5 variables for sex diagnosis have been obtained and these variables are highly significant. The discriminant rate for the group of 5 variables resulted in accurate sex determination in 96.7% of cases. For the group of 14 variables there was 100% success rate. PMID- 1639280 TI - Toxicological screen on gastric aspirates: the Singapore experience. AB - In the early eighties, in response to increasing self-poisoning incidents by pharmaceuticals in Singapore, a comprehensive wide-sweep screen for these drugs in clinical gastric aspirates was devised and implemented by us. The toxicological screen which involved quadruplicate extractions, two in acidic conditions and the other two in alkaline conditions, required the following analyses to be carried out: UV on the acidic fraction, TLC on the basic fraction and mega-bore capillary GC/NPD (nitrogen phosphorus detector) on the combined fraction. The combined fraction if necessary was subjected to GC/MS analysis. Our screen satisfied the need to confirm the analytical outcome of one method by another. Combining the acidic and basic fractions for a single GC analysis saves on instrument time and manpower. All coma and emergency cases were required to undergo GC/MS analysis to prove the identity of toxic agents beyond reasonable doubt. Quality control procedures were instituted at key steps to ensure quality of analytical outcome. PMID- 1639281 TI - The use of either the nose or outer ear as a means of determining the postmortem period of a human corpse. AB - Presented in this paper are the initial results involving the use of the nose or outer ear as temperature measurement sites to determine the postmortem period of the human corpse. Simple mathematical models for both sites are developed based on cooling curves of five corpses. Analysis of errors between actual and calculated postmortem intervals suggest that in its present form, the described methods would not be suitable for use in accurately determining the time since death of human corpses. PMID- 1639282 TI - Rapid isolation with Sep-Pak C18 cartridges and capillary gas chromatography of triazine herbicides in human body fluids. AB - A simple and rapid method, for the isolation of eight triazine herbicides from human serum and urine, using Sep-Pak C18 cartridges is presented. After mixing with distilled water, serum and urine samples containing the herbicides, were loaded on Sep-Pak C18 cartridges and eluted with either chloroform only or chloroform/methanol (9:1). The herbicides were detected by capillary gas chromatography with both flame ionization detection (FID) and nitrogen-phosphorus detection (NPD). Separation of eight triazine herbicides from each other and from impurities was generally satisfactory with the use of a non-polar DB-1 capillary column. Recovery of most compounds was excellent for both chloroform and chloroform/methanol (9:1) as elution solvents. Backgrounds were cleaner and evaporation time was shorter for the chloroform only than for the chloroform/methanol (9:1). The NPD gave sensitivity more than 10-20 times higher than that of FID. PMID- 1639283 TI - Flow cytometric studies in spontaneous abortions. Applications in the medico legal practice. AB - In the medico-legal practice differential diagnosis between spontaneous and non spontaneous abortion is important because causes of pregnancy wastage are often obscure and, moreover, spontaneous abortion is more common than accidental or voluntary. In all the cases in which the cause of abortion is not otherwise detectable and especially in cases of discovery of fetal adnexa, it is necessary to investigate genetic causes. Recently, DNA flow cytometric analysis has been applied in determining the genetic causes of spontaneous abortions. Among karyotypic abnormalities, flow cytometric analysis on paraffin embedded material can detect only polyploidies (triploidy and tetraploidy). Trisomies, monosomies and structural anomalies cannot be detected. In our study we tried to establish whether flow cytometry could be useful in determining the genetic cause of spontaneous abortions, in the lack of any other detectable cause. Histologic examination and flow cytometric analysis were performed on a series of 395 consecutive spontaneous abortions. Histologic examination allowed the detection of a molar pattern in about 9% of cases. DNA flow cytometric analysis showed diploidy in 346 (87.59%) cases, triploidy in 37 (9.36%) cases and tetraploidy in 12 (3.03%) cases. Combined microscopic and flow cytometric analysis revealed abnormalities in 17.5% of cases. A non-diploid pattern is more frequent in molar cases (P less than 0.001). Flow cytometry seems to be interesting in forensic pathology, as it allows the detection of some frequent genetic abnormalities in dead tissues and cells, when other techniques are no longer practicable. PMID- 1639284 TI - A high endrin concentration in a fatal case. AB - Gas chromatography coupled to mass spectrometry was employed to quantify endrin in biological fluids in a death attributed to endrin overdose. The blood concentration of endrin was 544.9 mg/l. Results are discussed in the light of the existing literature. PMID- 1639285 TI - Is mummification possible in snow? PMID- 1639286 TI - [Therapy of mouth cancer. 41st annual meeting of the German Association for Oral, Mandibular and Facial Surgery. Wurzburg]. PMID- 1639287 TI - [The epidemiology of lip and mouth malignancies]. PMID- 1639288 TI - [Statistical aspects of survival analysis in head-neck tumors]. PMID- 1639289 TI - [Mandible resection in mouth cancer--rim resection versus continuity resection]. PMID- 1639291 TI - [Radical neck dissection versus conservative neck dissection. A statistical evaluation of literature data]. PMID- 1639290 TI - [Saving the mandible in surgical treatment of mouth floor cancer]. PMID- 1639292 TI - [4th German-Austrian-Swiss Study Group therapy study. Prospective, randomized, clinical study of squamous cell cancer of the mouth: "Radical neck dissection versus conservative neck dissection"]. PMID- 1639293 TI - [The problem of elective (preventive) neck dissection in mouth cancer exemplified by a comparison of pre- and postoperative neck lymph node findings]. PMID- 1639294 TI - [Significance of lymph node staging in the trigonum caroticum in supra-hyoid lymph node excision]. PMID- 1639295 TI - [Morphologic and functional changes in the shoulder girdle after neck dissection]. PMID- 1639296 TI - [Modification of neck lymph node dissection in squamous cell cancers of the oral cavity]. PMID- 1639297 TI - [Maxillary cancers--a retrospective study]. PMID- 1639298 TI - [Preoperative radio-chemotherapy and radical operation of advanced mouth cancers- final results of a prospective therapy study of the German-Austrian-Swiss Study Group]. PMID- 1639299 TI - [Preoperative short-term preliminary irradiation with 3 x 6 Gy, immediate radical tumor resection and postoperative booster irradiation to 60 Gy as an effective therapy concept for the treatment of T2 squamous cell carcinomas of the mouth. Results of a prospective randomized bi-center study]. PMID- 1639300 TI - [Has preoperative irradiation of mouth cancer produced advantageous results?]. PMID- 1639301 TI - [Combined radiochemotherapy with cis-DDP and radical resection in patients with operable squamous cell cancers of the oropharynx. Results of 4 years of treatment of 132 patients]. PMID- 1639302 TI - [Causes and time of fatal events after therapy of mouth cancer]. PMID- 1639303 TI - [5-year survival rate of patients with squamous cell cancers of the mouth; a retrospective comparative study]. PMID- 1639304 TI - [Importance of clinical observation studies of the German-Austrian-Swiss Study Group for the oncology of mouth cancer]. PMID- 1639305 TI - [10 years study of the recurrence behavior and survival after radical surgery of not pre-treated mouth cancer]. PMID- 1639306 TI - [Statistical results in patients with squamous cell cancer of the mouth, 1981 1990 patient sample]. PMID- 1639307 TI - [Onco-surgical radical treatment, recurrence and rehabilitation in the Jena Clinic patient sample (1968-1989)]. PMID- 1639308 TI - [Comparative studies of two patient groups with primary mouth cancer 1981 to 1989]. PMID- 1639309 TI - [Long-term results of radical therapy of squamous cell cancers of the mouth with special reference to late recurrence and second malignancies--a catamnestic study of 20 years]. PMID- 1639310 TI - [Results of operative treatment of squamous cell cancers of the mouth and oropharynx with and without additional postoperative therapy]. PMID- 1639311 TI - [Change in the prognosis of surgically treated cancer of the mouth mucosa in the course of time]. PMID- 1639312 TI - [Possibilities and limits of the CIP (computer-assisted individual prognosis) program in clinical oncology]. PMID- 1639313 TI - [From the oncologic viewpoint is there an indication for immediate reconstruction in oral cancer?]. PMID- 1639314 TI - [Mouth cancer--intra-oral tumor resection]. PMID- 1639315 TI - [Individualized tumor therapy based on biological parameters and prognostic evaluation using the TPI (therapy-oriented prognostic index)]. PMID- 1639316 TI - [Survival of patients with mouth cancer in relation to age and concomitant diseases]. PMID- 1639317 TI - [Verrucous cancer of the mouth]. PMID- 1639318 TI - [Multiple primary malignant tumors in the area of the jaw, face and upper aerodigestive tract]. PMID- 1639319 TI - [Results of treatment of lip cancer]. PMID- 1639320 TI - [Functional and esthetic aspects of therapy for lip cancer]. PMID- 1639321 TI - [Results of surgical therapy of regional lymph nodes in lower lip cancer]. PMID- 1639322 TI - [Treatment concepts in surgical therapy of lip cancer]. PMID- 1639324 TI - [Determining indications for primary removal of regional lymph drainage vessels in lip cancer]. PMID- 1639323 TI - [Two years clinical documentation of head-neck tumors in the central tumor registry of the German-Austrian-Swiss Study Group]. PMID- 1639325 TI - [Survival rate and functional results after microsurgical reconstruction procedures in the area of the oral cavity]. PMID- 1639326 TI - [Effect of modern reconstruction procedures on radicality and survival time in mouth cancer]. PMID- 1639327 TI - [Survival rate of patients with jejunum transplants in comparison with the prospective German-Austrian-Swiss Study Group study]. PMID- 1639328 TI - [Primary defect coverage of mouth cancers by musculocutaneous flaps--results of a follow-up study]. PMID- 1639329 TI - [Does defect coverage with extensive flaps after surgery for advanced oral cancer have an effect on survival rate of patients?]. PMID- 1639330 TI - [Retrospective analysis of a mandible sparing therapy concept in cancers of the mouth floor]. PMID- 1639332 TI - Transcatheter ablation of cardiac tissue: advantages and disadvantages of different ablative techniques. AB - Transcatheter ablation techniques are emerging as an alternative therapeutical tool in the management of cardiac arrhythmias. Catheter ablation was initially introduced as the last resort to ablate the atrioventricular nodal conduction in patients with atrial fibrillation and uncontrolled ventricular response and in patients with drug refractory ventricular tachycardias. Direct current energy was used as the sole source of energy, but because of potential significant complications and early and late mortality, presumably mostly due to ventricular tachyarrhythmias, other sources of energy were sought. Radiofrequency current which does not produce barotrauma and does not require general anesthesia rapidly replaced direct current ablation in many centers. Early results with radiofrequency current ablation of the atrioventricular node and accessory atrioventricular pathways are very encouraging. The results of radiofrequency as well as direct current ablation for atrial flutter, atrial tachycardia and ventricular tachycardia, where the components of reentry circuit are less defined, are not as favorable as those of AV junctional tachycardias. However, improvement of catheter and generatory technology and better understanding of the mechanisms of ventricular tachycardias and characteristics of the target site will enhance the results of catheter ablation in ventricular tachcardias. The procedures are still considered investigational, and mostly done by very experienced groups at tertiary referral hospitals with surgical teams available in case of serious complications. Larger patient populations and longer follow-up periods are required before these techniques expand to community hospitals and to patients with minimal symptoms or asymptomatic individuals as a prophylaxis therapy. PMID- 1639331 TI - [Indications for partial mandibular resection in tumors of the mouth floor]. PMID- 1639333 TI - Transcatheter modification of the atrioventricular node using radiofrequency energy. AB - 120 consecutive patients with symptomatic atrioventricular nodal reentrant tachycardia (AVNRT) underwent catheter ablation using radiofrequency energy. Fast pathway ablation was attempted in the first 16 consecutive patients by application of radiofrequency current in the anterior and superior aspect of the tricuspid annulus. Successful results were accomplished in 13 patients, complete AV block occurred in three. The other 104 patients initially underwent ablation of the slow pathway in the posterior and inferior aspects of the tricuspid annulus which was successful in 98 patients. The remaining six patients subsequently underwent a fast pathway ablation with successful results in four and AV block in two. Therefore, 102 (98%) of the last 104 patients became free of AVNRT while maintaining intact AV conduction. This study demonstrates that both AV nodal conduction pathways can be selectively ablated. However, slow pathway ablation seems safer and should be considered as the first approach. PMID- 1639334 TI - Current status of radiofrequency ablation in the preexcitation syndromes. AB - Catheter ablation techniques have become an accepted treatment form for a variety of supraventricular arrhythmias. After the introduction of radiofrequency energy, catheter ablation has become the first line of treatment and has replaced surgery in patients with the preexcitation syndromes. The success rate in large series is very high, while the complication rate in experienced hands is very low. Despite all this progress, the ablation of a small subset of accessory atrioventricular pathways poses some problems. The ideal source of energy is still unknown and improvement in catheter technology are needed. This review will try to focus on some of these issues dealing with a very exciting area of clinical cardiology. PMID- 1639335 TI - Identifying sites for catheter ablation of ventricular tachycardia. AB - The approach to localizing sites for catheter ablation of ventricular tachycardia foci depends on the type of tachycardia. In large reentry circuits such as those arising from infarct scars, areas of slow conduction in and around the scar should be targeted. During sinus rhythm, these can be suspected from the presence of fractionated electrograms and, at some sites, long stimulus to QRS delays during pacing. Slow conduction areas can be classified as: 1. central slow conduction zone sites, 2. exits from the slow conduction zone, 3. entrances to the slow conduction zone, and 4. bystander areas which are not involved in the tachycardia circuit. In the central slow conduction zone stimulation entrains or resets tachycardia with a long stimulus to QRS (S-QRS) delay (40 to greater than 300 ms) without altering the QRS morphology (entrainment with concealed fusion). At slow conduction zone exits, presystolic electrograms are recorded during VT, the pacemap matches the VT QRS morphology, and with pacing during VT the S-QRS interval is relatively short and VT may or may not be entrained. At entrances to the slow conduction zone electrogram timing is variable but early diastolic electrograms are expected and the pace-map QRS may differ from the VT QRS morphology. Relatively late stimuli or slow trains of stimuli entrain VT with concealed fusion with a relatively longer S-QRS interval than observed in the central slow conduction zone. Early stimuli may entrain VT while altering the QRS morphology due to propagation of the stimulated antidromic wavefront out of the scar from a site other than the tachycardia exit. At bystander sites electrogram timing, pace-mapping, and the effects of programmed stimulation are variable but may occasionally mimic reentry circuit sites. Relatively late stimuli are likely to capture the site without altering the VT. If discrete electrograms are present, analysis of these during pacing may provide further evidence that the site is not in the reentry circuit. Catheter ablation will probably be most effective at central slow conduction zone sites. When VT originates from a small focus surrounded by normal myocardium, such as is likely for idiopathic RV outflow tract and some idiopathic left ventricular tachycardias, presystolic electrical activity and pacemapping are likely to identify the tachycardia focus. For macroreentry involving the bundle branches, the right bundle branch can be easily targeted. PMID- 1639336 TI - Catheter ablation of ventricular tachycardia using radiofrequency current. AB - Catheter ablation techniques have evolved as an alternative to map-guided surgery and proven effective in a variety of supraventricular tachyarrhythmias. Direct current catheter ablation has been shown to be effective in about 50 to 70% of cases. Approximately, 60% of patients with structural heart disease and monomorphic ventricular tachycardia were successfully treated using direct current ablation techniques. This overall success rate and possible risks associated with the use of direct current have stimulated the search for other energy sources appropriate for catheter ablation. Presently, only a few preliminary reports on the clinical efficacy of radiofrequency energy for the treatment of ventricular tachyarrhythmias in man exist. 23 patients with identifiable heart disease at a mean age of 52 +/- 17 years underwent radiofrequency catheter ablation. 16 patients had coronary artery disease, one patient dilative cardiomyopathy and six patients had arrhythmogenic right ventricular disease. All patients presented with chronic current sustained ventricular tachycardia. After detailed endocardial catheter mapping radiofrequency energy was applied at the site of earliest ventricular activation during ventricular tachycardia which could be entrained during fixed rate ventricular pacing at the site of origin of ventricular tachycardia. At all ablation sites a long latency between the stimulus and QRS complex was noted. Of 23 patients 18 were treated with radiofrequency alone whereas in five patients a second ablation procedure using direct current was performed. Following the ablation procedures, 14 patients (61%) remained free of ventricular tachycardia. One patient died due to congestive heart failure 21 months following ablation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639337 TI - Catheter ablation of ventricular tachycardia using radiofrequency techniques in patients without structural heart disease. AB - It has been previously demonstrated that radiofrequency (RF) energy can be safely applied to successfully eliminate accessory pathways in patients with the Wolff Parkinson-White syndrome. This technique may also be used to successfully eliminate atrioventricular (AV) nodal reentrant tachycardia by elimination of either the fast or slow AV nodal pathways. However, RF energy has achieved only limited success in eliminating ventricular tachycardia (VT) in patients with structural heart disease, such as coronary artery disease and dilated cardiomyopathy. Direct-current catheter techniques have successfully eliminated VT in patients with and without structural heart disease, but this technique is limited by the risk of barotrauma and proarrhythmia. We used RF catheter ablation techniques to eliminate VT in patients without structural heart disease. Our results from the basis of this report. 16 patients (nine women and seven men; mean age 38; range 18 to 55 years) who did not have any identifiable structural heart disease by echocardiography where included in this study. These patients underwent RF catheter ablation to eliminate VT. Two patients had presented with syncope, nine with presyncope and five with palpitations only. The mean duration of symptoms was 6.7 years (range 0.5 to 20 years). VT was successfully eliminated by RF catheter techniques in 15 of the 16 patients (a 94% success rate). Importantly, successful ablation sites included regions other than the right ventricular outflow tract. Areas of VT origin therefore included the high right ventricular outflow tract (twelve patients), right ventricular septum near the tricuspid valve (three patients), and the left ventricular septum (one patient). The only ablation failure was in a patient whose VT arose from a region near the His bundle. Successful ablation occurred in patients in whom an accurate pace map could be obtained and early local endocardial activation was obtainable. Further, firm catheter contact with endocardium was required for successful elimination of VT. RF ablation did not cause any identifiable arrhythmia and produced a minimal cardiac enzyme rise. It also resulted in no detectable change in cardiac function by Doppler echocardiography. Based on these findings, we conclude that RF catheter ablation of VT in patients without structural heart disease was highly effective and safe. It may therefore be considered as early therapy in these patients. PMID- 1639339 TI - Hormonal status of postmenopausal women with alcohol-induced cirrhosis: further findings and a review of the literature. AB - The derangements of levels of sex hormones and gonadotropins in alcoholic cirrhotic men are well delineated. The countersituation in alcoholic cirrhotic women has not yet been fully described. This study was performed in postmenopausal women among whom menstrual cycle variations in hormones no longer occur; with such a study population, it is possible to control for confounding factors and thus optimize detection of differences in levels of hormones and hormone interrelationships. Both estradiol levels and a rough estimate of aromatization of testosterone to estradiol, the estradiol to testosterone ratio, were significantly elevated in the 20 alcoholic subjects with alcohol-induced cirrhosis, as compared with the 27 normal controls; similarly, testosterone, luteinizing hormone and follicle-stimulating hormone were all significantly reduced in the alcoholic cirrhotic women. In addition, the normal relationships of estradiol with luteinizing hormone, follicle-stimulating hormone, body mass and the estradiol/testosterone ratio were detected in the control group but not in the group of cirrhotic women. Further, among the alcoholic cirrhotic postmenopausal women, testosterone, luteinizing hormone, follicle-stimulating hormone and the estradiol/testosterone ratio were all significantly correlated with the Child's liver disease severity score. That the hormone levels and their interrelationships differ markedly between normal and alcoholic cirrhotic women extends previous findings in both men and postmenopausal women; the correlations of hormone levels and markers of liver disease will require further investigation. PMID- 1639338 TI - [Long-term results of Mustard operation in transposition of the great arteries. Angiographic and nuclear medicine study of ventricular function]. AB - The fate of the right ventricle as systemic ventricle after atrial repair of complete transposition of the great arteries has not been clearly elucidated. In order to assess the long-term results of the Mustard operation in patients with complete transposition of the great arteries we present the clinical data of 23 patients who had been operated in the years 1974 and 1975. Twenty of these patients had simple complete transposition of the great arteries with intact ventricular septum, two had an additional small ventricular septal defect and one an additional left ventricular outflow tract obstruction with a 40 mm Hg systolic pressure gradient. The Mustard operation had been performed at a mean age of 2.2 (1 to 3.7) years. Seventeen of the 23 patients underwent a postoperative hemodynamic study with angiocardiography 1.1 (1 to 1.8) years following surgery. At that time the right ventricular ejection fraction, which had been calculated from biplane angiographic right ventricular volume measurements in twelve patients was 62 (52 to 68) %. However the right ventricle was dilated and the mean enddiastolic volume was 132 (108 to 192) % of normal. In twelve of the 23 patients right ventricular function was reassessed 12.6 (11 to 15.3) years after surgery by Technetium-99m-scintigraphy at rest and in ten of those after exercise with a workload of 2 watt/kg. The mean ejection fraction was 51 (38 to 66) % at rest and 52 (40 to 80) % during exercise. Only three patients had a normal response to exercise, which was defined as an increase of ejection fraction with exercise of more than 5%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639340 TI - Cholesterol metabolism in human gallbladder mucosa: relationship to cholesterol gallstone disease and effects of chenodeoxycholic acid and ursodeoxycholic acid treatment. AB - The objective of this study was to investigate cholesterol metabolism in human gallbladder mucosa, especially in relation to hepatic cholesterol metabolism, gallstone disease and treatment with bile acids. Gallbladder mucosa and liver tissue samples were collected in 44 patients undergoing cholecystectomy; 30 had cholesterol gallstones and the rest were stone free. Ten of the gallstone patients were treated with chenodeoxycholic acid and eight received ursodeoxycholic acid, with a daily dose of 15 mg/kg body wt, for 3 wk before surgery. The 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, governing cholesterol synthesis, was considerably lower in the gallbladder mucosa than in liver tissue (28 +/- 6 and 120 +/- 40 pmol/min/mg protein). The acyl coenzyme A:acyltransferase activity in the gallbladder mucosa catalyzing the esterification of cholesterol was, on the other hand, several times higher than corresponding activity in the liver (92 +/- 23 and 11 +/- 2 pmol/min/mg protein). In the presence of exogenous cholesterol, the acyl coenzyme A:acyltransferase activity increased about twofold in the gallbladder mucosa. The acyl coenzyme A:acyltransferase activity of the gallbladder mucosa from untreated gallstone patients was not stimulated further by the addition of exogenous cholesterol. Otherwise, there were no significant differences in acyl coenzyme A:acyltransferase and 3-hydroxy-3-methylglutaryl coenzyme A reductase activities in the gallbladder mucosa of gallstone patients compared with gallstone-free controls. Treatment with chenodeoxycholic and ursodeoxycholic acids did not affect the 3-hydroxy-3-methylglutaryl coenzyme A reductase activity of the gallbladder mucosa but reduced the acyl coenzyme A:acyltransferase activity by 60% to 65%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639341 TI - Postinfantile giant-cell transformation in hepatitis. AB - Giant-cell hepatitis is a frequent pattern of liver injury in the neonate, but it is rare after infancy. Such cases have been attributed to autoimmune disease, to non-A, non-B hepatitis and, most recently, to paramyxovirus infection. To better define the entity of postinfantile (syncytial) giant-cell hepatitis, we reviewed 24 biopsy specimens from 20 patients with this finding, either alone or in combination with other diagnoses. The number of multinucleated giant cells varied greatly from one specimen to another. Varying degrees of portal inflammation appeared in all but one of the patients, and all had hepatitislike acinar inflammation associated with hepatocellular injury. Fibrosis was a common finding, varying from mild periportal fibrosis to established cirrhosis (33%). The changes were interpreted as acute giant-cell hepatitis in 25%, as CAH in 42% and as active cirrhosis in the remainder. The patients ranged in age from 2 to 80 yr, with a mean of 35 yr and a male/female ratio of approximately 1:1. The signs and symptoms of liver disease were present for more than 1 mo in most patients. A positive antinuclear antibody titer was found in seven of the patients. Three patients had a direct Coombs reaction and anemia. Overall, evidence of autoimmune disease was found in 40% of the patients. One patient had non-Hodgkin's lymphoma involving the liver. Only one patient had a history of blood transfusion or risk factors for hepatitis C. No patient underwent serological study for paramyxovirus antibodies. Liver tissue from one patient was examined ultrastructurally, but no viral particles could be identified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639342 TI - Cystic dilatation of peribiliary glands in livers with adult polycystic disease and livers with solitary nonparasitic cysts: an autopsy study. AB - Cystic dilatation of peribiliary glands of intrahepatic and extrahepatic bile ducts was investigated in autopsied livers with adult polycystic disease (n = 8), in autopsied livers with solitary nonparasitic cysts (n = 18) and in normal autopsied livers (n = 23). In normal livers, cystic dilatation of intrahepatic peribiliary glands was absent or slight, when present. In livers with solitary nonparasitic cysts, cystic dilatation of intrahepatic peribiliary glands was present in varying degrees. In livers with adult polycystic disease, intrahepatic peribiliary glands showed frequent and severe cystic dilatation so marked that it was grossly recognizable. In contrast, peribiliary glands of the extrahepatic bile ducts showed no cystic dilatation in most cases, regardless of the three conditions examined. Liver parenchymal cysts were numerous in livers with adult polycystic disease, few in livers with solitary nonparasitic cysts and nonexistent in normal livers. Von Meyenburg complexes were present in 87.5% of livers with adult polycystic disease, in 16.7% of livers with solitary nonparasitic cysts and in 4.3% of normal livers. These findings suggest that intrahepatic peribiliary glands undergo cystic dilatation in livers with adult polycystic disease-and, to a lesser degree and frequency in livers with solitary nonparasitic cysts, probably because of congenital or genetic factors-and that these cystic changes may comprise a part of numerous cysts of adult polycystic disease. PMID- 1639343 TI - Metabolism of 15N-ammonia in patients with cirrhosis: a three-compartmental analysis. AB - Urinary 15N-ammonia and 15N-urea were measured by gas chromatography-mass spectrometry after the intravenous administration of 15N-ammonia (0.2 mumol/kg/hr) to 6 volunteers and 11 patients with cirrhosis. Urinary 15N-nitrogen excretion as ammonia and urea was measured during the 210-min infusion period, and urea synthesis and ammonia conversion to amino acids were analyzed with a three-compartment model using the nonlinear least-squares method. The rate of urea synthesis in control subjects was 14.1 +/- 1.2 mg/kg/hr (mean +/- S.E.M.), and in cirrhotic patients it was 11.0 +/- 3.2 mg/kg/hr. The cirrhotic group was divided into those with compensated cirrhosis (Child class A patients) and those with decompensated cirrhosis (Child classes B and C patients), and the rates of urea synthesis for these groups were 14.5 +/- 1.5 and 8.9 +/- 1.6 mg/kg/hr, respectively. The difference between decompensated cirrhotic patients and control subjects was statistically significant (p less than 0.001). The percentage of ammonia reutilization of a given dose of 15N-ammonia was 75.9% +/- 2.4% in compensated cirrhotic patients and 82.9% +/- 3.6% in decompensated cirrhotic patients (p less than 0.05). Fasting venous ammonia levels correlated inversely with urea synthesis (p less than 0.001) and correlated positively with ammonia reutilization (p less than 0.05). These results are consistent with a decreased capacity to synthesize urea and an increased capacity to convert ammonia to amino acids in chronic liver failure. PMID- 1639344 TI - Immunomodulatory effects of ursodeoxycholic acid on immune responses. AB - Ursodeoxycholic acid was recently recognized as an effective agent in the treatment of primary biliary cirrhosis. Experimental evidence supporting the usefulness of ursodeoxycholic acid as a potentially beneficial therapeutic agent for primary biliary cirrhosis has been reported from the biochemical and physiological aspects. In this study, we investigated the direct effects of ursodeoxycholic acid on immunoglobulin and cytokine production in vitro using plaque-forming cell assay and enzyme-linked immunosorbent assay. It was demonstrated that ursodeoxycholic acid suppressed the production of IgM, IgG and IgA induced by Staphylococcus aureus Cowan I in peripheral blood mononuclear cells derived from healthy subjects and patients with primary biliary cirrhosis and also in human B lymphoma cell lines. Furthermore, ursodeoxycholic acid suppressed interleukin-2 and interleukin-4 production induced by concanavalin A and interferon-gamma production induced by polyinosinic-polycytidylic acid, but it did not affect interleukin-1 and interleukin-6 production induced by lipopolysaccharide in peripheral blood mononuclear cells. In addition, ursodeoxycholic acid suppressed the concanavalin A-induced thymocyte proliferation mediated by interleukin-1. Cytotoxicity against lymphocytes was not observed at the concentrations of ursodeoxycholic acid used. These results suggest that the beneficial effect of ursodeoxycholic acid in primary biliary cirrhosis is mediated in part by immunosuppression. PMID- 1639345 TI - Purification of 3 alpha-hydroxysteroid and 3 beta-hydroxysteroid dehydrogenases from human liver cytosol. AB - We previously reported that the human Y' bile acid binder, which has higher bile acid binding affinities than rat Y' binders (3 alpha-hydroxysteroid dehydrogenases), has dihydrodiol dehydrogenase activity and is different from 3 alpha-hydroxysteroid dehydrogenases. In this study, 3 alpha-hydroxysteroid dehydrogenases and 3 beta-hydroxysteroid dehydrogenase were purified from human liver, and bile acid binding affinities and enzyme kinetics of the 3 alpha hydroxysteroid dehydrogenases were studied. On chromatofocusing of pooled Affigel blue fraction of the Y' fraction, three 3 alpha-hydroxysteroid dehydrogenase peaks eluted at pH 6.0, 5.7 and 5.4. These peaks did not bind bile acids, and further purification by hydroxyapatite-high-performance liquid chromatography gave pure 3 alpha-hydroxysteroid dehydrogenases with identical M(r) (36,000) having dihydrodiol dehydrogenase activity. 3 beta-Hydroxysteroid dehydrogenase was eluted together with Y' bile acid binder at pH 7.2 on chromatofocusing and was separated from Y' bile acid binder on hydroxyapatite-high-performance liquid chromatography as a pure protein with M(r) 32,000. The apparent Kms of 3 alpha hydroxysteroid dehydrogenases were similar to those of rat enzymes. In conclusion, we purified human hepatic 3 alpha-hydroxysteroid dehydrogenases, which have similar characteristics to rat enzymes, but do not bind bile acids or reduce bile acid precursors. These data further support the importance of human bile acid binder in intracellular bile acid transport in the human liver. PMID- 1639346 TI - Bile-duct destruction and collagen deposition: a prominent ultrastructural feature of the liver in cystic fibrosis. AB - To study the liver disease of patients with cystic fibrosis, percutaneous liver biopsies were performed in 10 patients with cystic fibrosis aged 6 to 22 yr. Nine of 10 patients had high Shwachman scores, eight had normal serum levels of transaminases. Light-microscopical examination showed steatosis in seven cases and in five slight or moderate inflammatory infiltration. Eight patients showed varying degrees of fibrosis and even cirrhosis. Six patients had bile-duct proliferation and, in one case a bile plug was found. Other signs of cholestasis were not seen. Electron-microscopical investigation showed no specific signs of cholestasis such as ductal plugs or intracellular bile pigments. The canaliculi were not dilated, except in one case. Most patients had bile-duct cells with irregular shapes, protruding into the lumen, and some cases even had necrotic cells. Around the bile ducts and ductules, collagen was deposited and fat-storing cells were a common finding. Our findings do not support the view that cholestasis is the pathogenetic factor in liver disease in cystic fibrosis. A cytotoxic influence on the biliary cells, stimulating collagen deposition, seems more likely. PMID- 1639347 TI - Expression of 27-kD heat-shock protein isoforms in human neoplastic and nonneoplastic liver tissues. AB - Previous study of rat liver during chemically induced hepatocarcinogenesis has shown that expression of isoforms of the 27-kD heat-shock protein was greater in neoplastic nodules and in hepatocellular carcinoma than in control livers. In this study, various human neoplastic and nonneoplastic liver tissues were investigated with electrophoresis after amino acid labeling to evaluate the expression of 27-kD heat-shock protein isoforms. This revealed that human liver contains 27-kD proteins that are recognized by a polyclonal antibody raised against human 27-kD heat-shock protein. Basal levels of fluorographical and immunostaining intensity of the 27-kD heat-shock protein spots (respectively, after [3H]leucine or 32P incorporation or as checked with a specific human 27-kD heat-shock protein antibody) were higher in hepatomas than in non-tumorous liver. Phosphorylation patterns of the 27-kD heat-shock protein isoforms were, however, similar in hepatocellular carcinoma and in uninvolved surrounding liver. Heat inducibility of the 27-kD heat-shock protein, tested in one case of liver cell adenoma and in the surrounding liver, was also preserved in both tissues. The role of the overexpression of 27-kD heat-shock protein in neoplastic liver tissues remains unknown. We propose, as a working hypothesis, that it is related to the resistant phenotype acquired by some tumors during malignant progression. PMID- 1639348 TI - Amino acid substitutions at position 38 of the DR beta polypeptide confer susceptibility to and protection from primary sclerosing cholangitis. AB - Previous studies based on serological HLA phenotyping have implicated genes in the HLA class II region in susceptibility to and protection from primary sclerosing cholangitis. In a recent report, the HLA DRw52a antigen was present in all 29 patients who had been referred for liver transplantation. In this study, HLA DRB, DQA and DQB genotypes were studied using gene amplification and sequence specific oligonucleotide probing in 71 patients with primary sclerosing cholangitis and 68 healthy controls to determine the frequency among the patients of the DRB3*0101 allele that encodes DRw52a and whether other class II alleles are involved in susceptibility or protection. DRB3*0101 was the most strongly associated allele, being present in 55% of the patients and 22% of the controls. Survival among the DRB3*0101-positive patients was reduced compared with the DRB3*0101-negative patients. Both DRB3*0101 and DRB5*0101, a possible second DRB susceptibility allele, encode a leucine residue at position 38 of the DR beta molecule. The DRB4*0101 allele, which encodes DRw53 and may be protective, encodes an alanine residue at this position. Susceptibility to and protection from primary sclerosing cholangitis may result from amino acid substitutions at position 38 of the DR beta molecule because maximum relative risk was conferred by two leucine-38-containing DR beta molecules, whereas minimum relative risk was conferred by two alanine-38-containing molecules. PMID- 1639349 TI - Globulin correction of the albumin gradient: correlation with measured serum to ascites colloid osmotic pressure gradients. AB - The albumin difference or gradient between serum ascites is presumed to be an effective estimate of the colloid osmotic pressure gradient, although this has never been directly demonstrated. The colloid osmotic pressure gradient is controlled by the degree of portal hypertension. Thus the albumin gradient is clinically useful in detecting patients with ascites caused by portal hypertension, although some overlap in such patients' albumin gradients exists compared with those of patients without portal hypertension. Part of this overlap is related to the inverse correlation of the albumin gradient with serum globulin; globulins also contribute to colloid osmotic pressure. The ability to calculate colloid osmotic pressure in serum and ascites with albumin and globulin concentration or to correct the albumin gradient for the impact of globulins might improve the clinical usefulness of the ascitic fluid analysis in determining the presence of portal hypertension in ascitic patients with borderline albumin gradients. Thus we developed equations to calculate colloid osmotic pressure from multivariate discriminate analyses of albumin and globulin concentrations in serial dilution samples of pooled serum and subsequently validated these equations, along with older methods of calculating colloid osmotic pressure. In an initial set of dilution experiments, globulin concentration was closely correlated with the colloid osmotic pressure to albumin concentration ratio (r = 0.956; p less than 0.001). Multivariate discriminate analysis yielded an equation for calculating colloid osmotic pressure from albumin (A) and globulin (G) concentration with a ratio of colloid osmotic pressure to albumin (calculated colloid osmotic pressure = A(1.058G + 0.163A + 3.11) and two other equations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639350 TI - Increased tissue-type plasminogen activator activity in orthotopic but not heterotopic liver transplantation: the role of the anhepatic period. AB - The major cause of the increased tissue-type plasminogen activator activity during orthotopic liver transplantation is still unclear. Both the lack of hepatic clearance of tissue-type plasminogen activator in the anhepatic period and increased endothelial release from the graft on reperfusion have been proposed as the major causes. Heterotopic liver transplantation avoids the resection of the host liver and is a useful model to help differentiate between these two possibilities. In this study the fibrinolytic system was evaluated in 10 orthotopic liver transplantations, 18 heterotopic liver transplantations and a control group of 10 partial hepatic resections. A marked increment in tissue-type plasminogen activator activity, from 0.2 to 5.2 IU/ml (p less than 0.02), was observed during the anhepatic period of orthotopic liver transplantation, which rapidly normalized after reperfusion. In contrast, tissue-type plasminogen activator activity levels remained normal in heterotopic liver transplantation and partial hepatic resections. In orthotopic liver transplantation and in heterotopic liver transplantation no increase occurred in tissue-type plasminogen activator activity after reperfusion. The first venous hepatic outflow after reperfusion did not contain elevated tissue-type plasminogen activator activity levels. Plasma degradation products of fibrin and fibrinogen increased during the anhepatic period of orthotopic liver transplantation (from 2.60 to 8.80 micrograms/ml [p less than 0.008] and from 0.40 to 1.60 micrograms/ml [p less than 0.04], respectively) and remained elevated thereafter. In heterotopic liver transplantation and partial hepatic resections these levels remained low. In conclusion, the lack of hepatic clearance during the anhepatic period is probably the most important factor in the evolution of increased tissue-type plasminogen activator activity during orthotopic liver transplantation. PMID- 1639351 TI - Administration of interleukin-2 induces major histocompatibility complex class II expression on the biliary epithelial cells, possibly through endogenous interferon-gamma production. AB - In various organ-specific autoimmune diseases, aberrant expression of major histocompatibility complex class II antigens on each target epithelial cell has been reported. Some researchers have attempted to link this phenomenon to the antigen-presenting capacity and the induction of autoimmunity, whereas others think it might serve as a peripheral mechanism for the induction and the maintenance of self-tolerance in autoreactive T cells. In this study, we showed that intraperitoneal administration of interleukin-2 (1.2 x 10(6) IU/kg) to 4-wk old male BALB/c mice for 35 consecutive days induced lymphocyte infiltration around bile ducts in the liver and major histocompatibility complex class II expression on biliary epithelial cells, which was immunoelectron microscopically confined to the luminal cell surface. Immunohistochemically, lymphocytes accumulating around bile ducts were mainly T cells, positive for CD3, L3T4 and H 2 class II molecules, and a few of them were positive for Lyt-2 and negative for immunoglobulin. Half of the infiltrates were positive for asialo GM1, and one third was positive for interferon-gamma. Interferon-gamma-positive, L3T4-positive cells were detected in mirror sections. However, neither the destruction of biliary epithelial cells nor the presence of granulomas was observed. Autoantibodies were serologically undetectable. The existence of interferon-gamma positive cells in the lesion and the fact that intravenous administration of anti interferon-gamma twice a week completely inhibited the lymphocyte infiltration and the major histocompatibility complex class II expression on biliary epithelial cells suggested that these changes were induced through endogenous interferon-gamma production.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639352 TI - Nodular regenerative hyperplasia in the rat induced by a selenium-enriched diet: study of a model. AB - Weaned male rats were fed a 4 ppm selenium diet. Compared after 2 mo with a control group fed a 0.4 ppm diet, the rats' body weights had not significantly decreased and liver function was normal, but portal pressure was 1.8 times higher (p less than 0.05). Liver weight was slightly increased (10.3%; p less than 0.05). All livers had an abnormal appearance. In the less severe cases the surface was only slightly irregular, but in the more severe cases, atrophic micronodular lobes and hypertrophic lobes, with mildly irregular surfaces, were present. On light microscopy, atrophic lobes displayed a peripheral nodular zone with micronodules separated by rows of atrophic hepatocytes without fibrosis, characteristic of nodular regenerative hyperplasia, and a central atrophic zone that was sometimes peliotic. Hypertrophic lobes and livers in the less severe cases had only minor and relatively localized evidence of nodular regenerative hyperplasia; occasional peliosis was seen. In all cases portal veins, hepatic veins and hepatic arteries were normal. By electron microscopy, in nonnodular zones with no obvious evidence of parenchymal atrophy, the endothelial wall showed signs of complete or incomplete capillarization with frequent enlargement of the Disse space. The selenium-enriched diet is a reproducible model of liver nodular regenerative hyperplasia. In this model, damage to the sinusoidal wall could represent the primum movens of microcirculatory disturbances. PMID- 1639353 TI - Spontaneously diabetic biobreeding rats and impairment of bile acid-independent bile flow and increased biliary bilirubin, calcium and lipid secretion. AB - Chemically induced diabetes has been reported to induce profound changes in bile formation, but possible toxic effects of the streptozotocin or alloxan used cannot be excluded totally. This study was undertaken to evaluate biliary function in spontaneously diabetic female biobreeding rats with a diabetes duration of 2 wk and compare them with nondiabetic littermates. Diabetic animals evidenced glycosuria, hyperglycemia and hypoinsulinemia. Biliary concentration and secretion of bile acids, cholesterol and phospholipids were significantly increased, with no enhancement in the lithogenic index of bile. Bile flow and the biliary secretion of sodium, potassium, chloride and bicarbonate were significantly reduced despite the increased bile acid secretion. The cholestatic condition was confirmed by an increased serum concentration of bile acids and a higher activity in serum of the alkaline phosphatase liver isoenzyme. Biliary calcium concentration increased without any change in its serum concentration. A linear relationship was observed between biliary calcium and bile acid secretion. Serum concentration of unconjugated and of conjugated bilirubin was increased 1.6 fold and 8-fold, respectively, with a 1.5-fold enhanced biliary secretion of bilirubins despite the cholestasis; this points to an enhanced bilirubin production. An increased proportion of conjugated bilirubin was found in serum together with an enhanced bilirubin diconjugate/monoconjugate ratio in bile. A higher UDP-glucuronyltransferase activity and a delayed transit of bilirubin could account for these effects. Administration of insulin to diabetic animals tended to reverse the above reported changes. The spontaneously diabetic biobreeding rat thus represents a model of bile acid-independent cholestasis with enhanced biliary bile acid and calcium secretion and with presumably an enhanced bilirubin production. PMID- 1639354 TI - Increased 4-hydroxynonenal levels in experimental alcoholic liver disease: association of lipid peroxidation with liver fibrogenesis. AB - The precise role of lipid peroxidation in the pathogenesis of alcoholic liver disease is still being debated. To explore the issue, this study was undertaken to investigate the status of lipid peroxidation, antioxidants and prooxidants at two discrete stages of experimental alcoholic liver disease. Male Wistar rats were intragastrically fed a high-fat diet plus ethanol for 5 or 16 wk (the duration that resulted in initiation of centrilobular liver necrosis or liver fibrosis, respectively). Lipid peroxidation was assessed in isolated microsomes and mitochondria with three parameters: malondialdehyde equivalents as determined by thiobarbituric acid assay, conjugated diene formation and 4-hydroxynonenal as a 2,4-dinitrophenylhydrazone derivative. To assess antioxidant systems, hepatic concentrations of glutathione, methionine and alpha-tocopherol were determined. The concentration of nonheme iron, a known prooxidant, was also measured. At wk 5, centrilobular liver necrosis was already evident in the ethanol-fed animals, with two- or threefold increases in plasma AST and ALT levels. At this stage, neither malondialdehyde equivalents nor conjugated diene values were elevated, and the 4-hydroxynonemal level was below 0.2 nmol/mg protein. Hepatic concentrations of methionine and alpha-tocopherol in these animals were increased two- and threefold, respectively, whereas the reduced glutathione level remained unchanged. When alcoholic liver disease had progressed to perivenular or bridging fibrosis at wk 16, all three parameters of lipid peroxidation showed consistent increases that were accompanied by significant reductions in the hepatic glutathione and methionine levels. Interestingly, the control animals pair-fed with the high-fat diet also had significantly elevated 4-hydroxynonenal levels at wk 16 compared to the wk 5 level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639355 TI - Ischemic injury in liver transplantation: difference in injury sites between warm and cold ischemia in rats. AB - Using liver allografts with warm or cold ischemia, we evaluated functional and morphological alterations in hepatocytes, sinusoidal endothelial cells and Kupffer cells in a rat transplantation model. All recipients of allografts with either 4 hr of cold or 30 min of warm ischemia lived more than 22 days and were judged viable. On the other hand, all recipients of grafts with 6 hr of cold or 60 min of warm ischemia died within 2 days and were therefore judged to be nonviable. With these viable and nonviable allograft models, hepatocyte function was evaluated by the bile output and serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase and serum lactate dehydrogenase levels; endothelial cell function was judged by the serum hyaluronic acid level, and Kupffer cell function was measured by an intravenous colloidal carbon clearance test. Hepatocyte injury was the prominent feature in warm ischemic grafts, especially in the nonviable ones. On the other hand, serum hyaluronic acid values were significantly higher in the nonviable cold ischemic group, compared with the viable counterpart, suggesting that the functional depression of endothelial cells was predominant in cold, nonviable livers. Histological examinations coincided with the above findings. The phagocytic activity of Kupffer cells was depressed by warm or cold ischemia, whereas the number of Kupffer cells was reduced in the warm ischemia group. We conclude that in liver allografts the main site of injury in warm ischemia is the hepatocytes and suggest that cold ischemia is associated with endothelial cell damage. PMID- 1639356 TI - Inhibition of hepatic metastasis of colon carcinoma by asialo GM1--positive cells in the liver. AB - This study investigates the role of hepatic asialo GM1-positive cells in inhibiting hepatic metastasis of colon carcinoma (colon adenocarcinoma 38) in mice after administration of a biological response modifier, streptococcal derivative (OK432). Administration of OK432 increased the number of asialo GM1 positive cells in the liver, enhanced natural killer activity of hepatic mononuclear cells and reduced the number of hepatic metastases of colon carcinoma inoculated into the superior mesenteric vein. Administration of antiserum against asialo GM1 reduced the number of hepatic asialo GM1-positive cells, abolished natural killer activity of hepatic mononuclear cells and increased the number of hepatic metastases. In addition, administration of antiserum against asialo GM1 even after OK432 treatment also decreased the number of asialo GM1-positive cells, reduced natural killer activity of hepatic mononuclear cells and increased the number of hepatic metastases of colon carcinoma. However, administration of gadolinium chloride, which suppresses phagocytic function of Kupffer cells, did not influence the natural killer activity of hepatic mononuclear cells or the number of hepatic metastases. In vivo tumor-neutralization assay revealed that tumor growth was inhibited by the hepatic mononuclear asialo GM1-positive cells, but not by T lymphocytes or Kupffer cells after OK432 administration. These results suggest that an increased number of hepatic asialo GM1-positive cells after administration of OK432 plays an important role in protecting against metastasis of colon carcinoma in the liver. PMID- 1639357 TI - Tumor necrosis factor and endotoxin in the pathogenesis of liver and pulmonary injuries after orthotopic liver transplantation in the rat. AB - This study examines whether tumor necrosis factor and endotoxin are involved in the pathogenesis of primary nonfunction of graft and pulmonary complication after orthotopic liver transplantation. Livers from Lewis rats were stored for either 1 or 4 hr in ice-cold Euro-Collins solution (1-hr storage and 4-hr storage group, respectively). Subsequently, donor livers were implanted orthotopically. In some experiments, anti-tumor necrosis factor antibody was administered intravenously before and immediately after the surgery into animals that received livers stored for 4 hr. Blood samples for the measurement of tumor necrosis factor and endotoxin were collected by way of an indwelling catheter placed in the suprahepatic vena cava. Serum tumor necrosis factor was elevated at all time points studied postoperatively in rats of the 4-hr storage group; however, tumor necrosis factor was not detected in the serum in the 1-hr storage group. Endotoxin was also elevated significantly in the serum of the former group compared with levels in the serum of the latter group. The peak value of endotoxin occurred 1 hr earlier than that of tumor necrosis factor, suggesting that the rise in endotoxin stimulated release of tumor necrosis factor. The histological study of livers stored for 4 hr showed substantial hepatocellular degeneration 24 hr after surgery, whereas hepatocellular damage was minimal in the 1-hr storage group. Serum ALT levels 24 hr after the operation in the 1-hr and 4-hr storage groups were 169 +/- 46 IU/L and 374 +/- 41 IU/L (mean +/- S.E.M., p less than 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639358 TI - Therapy of acute hepatitis C with interferon: how good is it really? PMID- 1639359 TI - The immune response in chronic hepatitis B virus infection: the "core" of the problem? PMID- 1639360 TI - An "ironic" case of mistaken identity? PMID- 1639361 TI - Efficacy of ursodeoxycholic acid in preventing cholestatic episodes in a patient with benign recurrent intrahepatic cholestasis. PMID- 1639363 TI - The International Association for the Study of the Liver. Biennial scientific meeting. Brighton, United Kingdom, June 3-6, 1992. Abstracts. PMID- 1639362 TI - Interferon-alpha therapy combined with nonsteroid antiinflammatory drugs for treatment of chronic viral hepatitis? PMID- 1639364 TI - Data watch. Office visits to specialists continue to increase. PMID- 1639365 TI - Beyond tech assessment: balancing needs, strategy. AB - Technology assessment is undergoing a profound transformation in some hospitals. Driven by diverse (and sometimes contradictory) pressures from consumers and payers for cutting-edge yet cost-effective care, hospitals are finding that the evaluation process is growing more complex. Experts say that a formalized assessment process can balance organizational goals and community needs. PMID- 1639366 TI - Out of chaos: a rational approach to assessing technology. PMID- 1639367 TI - Women's, children's groups say reform debate ignores needs. AB - In putting their plans on the table, some health care reformers are forgetting the needs of women and children, advocates for those groups say. Meanwhile, hospitals are collaborating in efforts to fulfill still-unmet health needs. PMID- 1639368 TI - Financial outlook: more mergers, new payer partnerships. PMID- 1639369 TI - First-quarter data show slower inflation, strong jobs growth. PMID- 1639370 TI - PROs, providers and physicians to collaborate on cardiac outcomes. PMID- 1639372 TI - NY hospital consortium takes high-tech turn. PMID- 1639371 TI - Tallahassee Memorial: focusing the culture on customer service. PMID- 1639373 TI - Managing the participatory-style meeting. PMID- 1639374 TI - Pain centers take many approaches to patient care. PMID- 1639375 TI - Joint Commission cracks down on falsified records. PMID- 1639376 TI - Image obsession: is it healthy for CEOs? PMID- 1639378 TI - Organization of the gene encoding the mouse T-cell-specific serine proteinase "granzyme A". AB - The mouse serine protease granzyme A is a member of a closely related family of T cell-associated proteolytic enzymes, designated granzymes A-G. Previous studies have indicated that granzymes A and B are involved in various T-cell-mediated processes. Here we report the genomic organization of the granzyme A gene. We have cloned a 15-kb DNA fragment from a genomic library of a cloned CD8+ T-cell line and sequenced the exon-intron boundaries. The gene consists of five exons, and its genomic organization is very similar to that described for granzymes B, C, and F. In addition, we have sequenced 1.4 kb of the 5'-region and 1.1 kb of the 3'-region flanking the granzyme A gene. Putative promoter and enhancer elements were identified by sequence comparison with known consensus sequences. Some of these regulatory elements seem to be associated exclusively with granzyme A, whereas others are shared by members of the granzyme family. PMID- 1639377 TI - Mapping the human liver/islet glucose transporter (GLUT2) gene within a genetic linkage map of chromosome 3q using a (CA)n dinucleotide repeat polymorphism and characterization of the polymorphism in three racial groups. AB - The human liver/islet glucose transporter (GLUT2), a candidate gene for diabetes, has been incorporated into a genetic linkage map for chromosome 3q using a (CA)n dinucleotide repeat polymorphism adjacent to the 3'-end of exon 4a. We have found a total of nine alleles ranging in length from 153 to 169 nucleotides in three racial groups and have determined the precise structure of the variable region for four of the alleles by DNA sequencing. Five alleles were found to be common to the American Black, Caucasian, and Pima Indian racial groups studied. One allele (169 bp) was unique to American Blacks, and another rare allele (153 bp) was found only in the Caucasian population studied. Observed heterozygosity of the polymorphism in the Caucasian (CEPH) reference pedigree collection is 60%, for American Blacks 71%, and for Pima Indians 53%. An independent study recently identified the same dinucleotide repeat and found six alleles in a Caucasian population (Froguel et al., 1991), a result that we confirm; however, our sequencing data indicate a different molecular structure for the polymorphism for some of the alleles. We have constructed a new genetic linkage map of chromosome 3q uniquely placing the GLUT2 gene between flanking markers D3S26 and D3S43. The genetic map consists of 23 loci (25 RFLPs and 2 (CA)n dinucleotide repeat markers) with 14 markers uniquely localized with odds of at least 1000:1. Three genes (FTHL4, TF, GLUT2) are integrated into the map, which spans a sex-average distance of 147.3 cM, 103.8 cM in males and 227.0 cM in females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639379 TI - Physical and genetic characterization of the distal segment of the myotonic dystrophy area on 19q. AB - The mutation involved in myotonic dystrophy (DM) has been mapped to the region between the ERCC1 DNA repair gene and the anonymous D19S51 locus on 19q13.3. Starting at locus D19S112 (probe pX75b), which served as a novel entry site for this chromosome region, we have established a cosmid contig of approximately 200 kb. In the contig, a gene expressed in the brain and a highly informative, 12 allele (TG)n variable simple sequence motif (VSSM) were identified. With this marker, designated X75b-VSSM, a highly characteristic size distribution of alleles linked with DM, which differed significantly from that on normal chromosomes, was observed. Combining our physical mapping and genetic data, we show that the X75b-VSSM marker is the closest distal to DM, thus excluding the DM mutation from the entire telomeric portion of the ERCC1-D19S51 region. PMID- 1639380 TI - Physical mapping and cloning of the proximal segment of the myotonic dystrophy gene region. AB - The myotonic dystrophy (DM) region has been recently shown to be bracketed by two key recombinant events. One recombinant occurs in a Dutch DM family, which maps the DM locus distal to the ERCC1 gene and D19S115 (pE0.8). The other recombinant event is in a French Canadian DM family, which maps DM proximal to D19S51 (p134c). To further resolve this region, we initiated a chromosome walk in a telomeric direction from pE0.8, a proximal marker tightly linked to DM, toward the genetic locus. An Alu-PCR approach to chromosome walking in a cosmid library from flow-sorted chromosome 19 was used to isolate DM region cosmids. This effort has resulted in the cloning of a 350-kb genomic contig of human chromosome 19q13.3. New genetic and physical mapping information has been generated using the newly cloned markers from this study. As a result of this new mapping information, the minimal area that is to contain the DM gene has been redefined. Approximately 200 kb of sequence between pE0.8 and the closest proximal marker to DM, pKEX0.8, that would have otherwise been screened for DM candidate genes, has been eliminated as containing the DM gene. PMID- 1639381 TI - Characterization of a YAC and cosmid contig containing markers tightly linked to the myotonic dystrophy locus on chromosome 19. AB - Myotonic dystrophy (DM) is caused by a defect in an unknown gene that maps to 19q13.3, flanked by the tightly linked markers ERCC1 on the proximal side and D19S51 on the distal side. We report the isolation and characterization of overlapping YAC and cosmid clones around D19S51 for the construction of a physical map around this locus. The resulting contig contains the markers D19S51 and D19S62 (another new marker tightly linked to the DM locus) and the distal breakpoint of a radiation hybrid cell line used in the physical mapping of the DM region. We have compared the restriction maps of the YACs and cosmids with that of the genome to investigate the fidelity of these clones. PMID- 1639382 TI - Continuous linkage map of human chromosome 14 short tandem repeat polymorphisms. AB - Nine moderately to highly informative short tandem repeat polymorphisms were assigned to chromosome 14 using somatic cell hybrids and were mapped using linkage analysis. The nine markers formed a continuous linkage map covering almost the entire long arm from 14q11.2 to q32. The markers filled a large gap within previously reported linkage maps for this chromosome. Best order of the new loci from q11.2 to q32 was D14S50, D14S54, D14S49, D14S47, D14S52, D14S53, D14S55, D14S48, and D14S51. The order shown for all adjacent pairs of loci was very strongly favored with the exception of loci pair D14S55 and D14S48, for which the order was moderately favored. Map lengths for the nine loci were 142 cM in females and 72 cM in males. Female recombination frequencies exceeded male recombination frequencies in the middle and distal portions of the map. PMID- 1639383 TI - Characterization of human adenylate kinase 3 (AK3) cDNA and mapping of the AK3 pseudogene to an intron of the NF1 gene. AB - We have isolated cDNA clones for human adenylate kinase isozyme 3 (AK3) with a genomic probe from the neurofibromatosis type 1 (NF1) region. Three overlapping clones isolated from a human frontal-cortex cDNA library gave rise to a consensus sequence of 1.7 kb. The open reading frame identified in this sequence predicted a peptide of 223 residues. A database search revealed striking homology, about 58% amino acid sequence identity, between this predicted protein and bovine AK3. Human AK3 protein also showed significant homology to other members of the adenylate kinase family isolated from various species. Genomic Southern analysis suggested that multiple AK3 loci exist in the human genome, including one located in an intron of NF1 on chromosome 17. The chromosome-17 locus appears to be a processed pseudogene, since it is intronless and contains a polyadenylate tract; it nevertheless retains coding potential because the open reading frame is not impaired by any observed base substitutions. PMID- 1639384 TI - Detection of point mutations and a gross deletion in six Hunter syndrome patients. AB - We have used screening with the polymerase chain reaction and chemical mismatch detection of amplified cDNA to detect and characterize deletions and point mutations in six Hunter Syndrome patients. A high degree of mutational heterogeneity was observed. The first patient is completely deleted for the gene coding for alpha-L-iduronate sulfate sulfatase, while the second has a point mutation that creates a stop codon. The third patient shows a point mutation that creates a novel splice site that is preferentially utilized and results in partial loss of one exon in the RNA. Patients 4, 5, and 6 have point mutations resulting in single amino acid substitutions. Four of the six single-base changes observed in this study were examples of transitions of the highly mutable dinucleotide CpG to TpG. This study has demonstrated a procedure capable of detecting all types of mutation that affect the function of the IDS protein and should enable direct carrier and prenatal diagnosis for Hunter syndrome families. PMID- 1639385 TI - Somatic cell hybrids, sequence-tagged sites, simple repeat polymorphisms, and yeast artificial chromosomes for physical and genetic mapping of proximal 17p. AB - Somatic cell hybrids retaining the deleted chromosome 17 from 15 unrelated Smith Magenis syndrome (SMS) [del(17)(p11.2p11.2)] patients were obtained by fusion of patient lymphoblasts with thymidine kinase-deficient rodent cell lines. Seventeen sequence-tagged sites (STSs) were developed from anonymous markers and cloned genes mapping to the short arm of chromosome 17. The STSs were used to determine the deletion status of these loci in these and four previously described human chromosome 17-retaining hybrids. Ten STSs were used to identify 28 yeast artificial chromosomes (YACs) from the St. Louis human genomic YAC library. Four of the 17 STSs identified simple repeat polymorphisms. The order and location of deletion breakpoints were confirmed and refined, and the regional assignment of several probes and cloned genes were determined. The cytogenetic band locations and relative order of six markers on 17p were established by fluorescence in situ hybridization mapping to metaphase chromosomes. The latter data confirmed and supplemented the somatic cell hybrid results. Most of the hybrids derived from [del(17)(p11.2p11.2)] patients demonstrated a similar pattern of deletion for the marker loci and were deleted for D17S446, D17S258, D17S29, D17S71, and D17S445. However, one of them demonstrated a unique pattern of deletion. This patient is deleted for several markers known to recognize a large DNA duplication associated with Charcot-Marie-Tooth (CMT) disease type 1A. These data suggest that the proximal junction of the CMT1A duplication is close to the distal breakpoint in [del(17)(p-11.2p11.2)] patients. PMID- 1639387 TI - Sequence, higher order repeat structure, and long-range organization of alpha satellite DNA specific to human chromosome 8. AB - We have characterized alphoid repeat clones derived from a chromosome 8 library. These clones are specific for human chromosome 8, as demonstrated by use of a somatic cell hybrid mapping panel and by in situ hybridization. Hybridization of the clones to HindIII digests of human genomic DNA reveals a complex pattern of fragments ranging in size from 1.3 to greater than 20 kb. One clone, which corresponds in size to the most prevalent genomic HindIII fragment, appears to represent a major higher order repeat in the chromosome 8 centromere. The DNA sequence of this clone reveals a dimeric organization of alphoid monomers. Restriction analysis of two other clones indicates that they are derivatives of this same repeat unit. The chromosome 8 alphoid clones hybridize to EcoRI fragments of genomic DNA ranging up to 1000 kb in length and reveal a high degree of polymorphism between chromosomes. Distribution of higher order repeat units across the centromere was examined by two-dimensional gel electrophoresis. Repeat units of the same size class tended to cluster together in restricted regions of centromeric DNA. PMID- 1639386 TI - A microsatellite polymorphism associated with the PLC1 (phospholipase C) locus: identification, mapping, and linkage to the MODY locus on chromosome 20. AB - A highly polymorphic (dC-dA)n.(dG-dT)n dinucleotide repeat at the PLC1 locus on human chromosome 20 has been identified. Primers flanking the dinucleotide repeat were used for PCR amplification of the repeat region in 37 informative kindreds from the Centre d'Etude du Polymorphisme Humain. Two-point linkage analysis indicates that PLC1 is closely linked to several chromosome 20 markers, including D20S16 (Zmax = 41.25; theta = 0.07), D20S17 (Zmax = 42.81; theta = 0.09), and ADA (Zmax = 57.24; theta = 0.05). Multipoint linkage analysis places the PLC1 locus between D20S18 and D20S17, 11.2 and 6.6 cM, respectively, from these loci (sex averaged distances). In addition, the PLC1 gene shows linkage to the maturity onset diabetes of the young (MODY) locus on chromosome 20 with a lod score of 4.57 at theta = 0.089. PMID- 1639388 TI - Structure and expression of the human p58clk-1 protein kinase chromosomal gene. AB - A cDNA corresponding to a 58-kDa cell division control-related protein kinase, p58clk-1, has previously been isolated, sequenced, and assigned to human chromosome 1p36. Aberrant expression of this protein kinase negatively regulates normal cellular growth. The p58clk-1 protein contains a central domain of 299 amino acids that is 46% identical to human p34cdc2, the master mitotic protein kinase. Deletion of 1p36 has been correlated to numerous tumors, and this chromosome region has been suggested to harbor a putative tumor suppressor gene on the basis of the growth characteristics of these tumors. In this report we detail the complete structure of the p58clk-1 chromosomal gene, including its putative promoter region, transcriptional start sites, exonic sequences, and intron/exon boundary sequences. The gene is 10 kb in size and contains 12 exons and 11 introns. Interestingly, the rather large 2.0-kb 3' untranslated region is interrupted by an intron that separates a region containing numerous AUUUA destabilization motifs from the coding region. Furthermore, we detail the expression of this gene in normal human tissues as well as several human tumor cell samples and lines. The origin of multiple human transcripts from the same chromosomal gene, and the possible differential stability of these various transcripts, is discussed with regard to the transcriptional and post transcriptional regulation of this gene. This is the first report of the chromosomal gene structure of a member of the p34cdc2 supergene family. PMID- 1639389 TI - Isolation and chromosomal assignment of 100 highly informative human simple sequence repeat polymorphisms. AB - One hundred highly informative simple sequence repeat (SSR) polymorphisms have been isolated and mapped to specific human chromosomes by somatic cell hybrid analysis. These markers include 97 (CA)n, 2 (AGAT)n, and a single (AACT)n repeat. All the SSRs have heterozygosities greater than 0.50 and can be amplified using identical PCR conditions. At least one SSR was detected on every chromosome, except for chromosomes 22 and Y. The frequency of (CA)n repeats on each chromosome was proportional to the relative chromosomal length, except for chromosome 15, on which a substantial excess of markers was identified. PMID- 1639390 TI - Genomic organization, sequence analysis, and chromosomal localization of the human carboxyl ester lipase (CEL) gene and a CEL-like (CELL) gene. AB - The gene encoding human carboxyl ester lipase (CEL), including 1628 bp of the 5' flanking region, has been isolated and characterized from two overlapping lambda phage clones. The gene spans 9832 bp and contains 11 exons interrupted by 10 introns. The exons range in size from 88 to 204 bp, except for the last exon, which is 841 bp. A major and a minor transcription initiation site were determined 13 and 7 bp, respectively, upstream of the initiator methionine. The nucleotide sequence is identical with that of the previously reported cDNA, except for the third nucleotide in the 5'-untranslated sequence, a C, which in the cDNA is a T. A TAAATA sequence is present 26 nt upstream from the major CAP site, and within the 5'-flanking region there are several putative transcription factor binding sites. Seven Alu repetitive sequence elements are present in the region analyzed. The organization of the human CEL gene is similar to that of the recently reported rat pancreatic cholesterol esterase gene. The CEL gene was assigned to chromosome 9q34-qter, which confirms the recently reported results of Tayler et al. (1991, Genomics 10: 425-431). A previously unknown gene with a striking homology to the human CEL gene, here called the CEL-like gene (CELL), has also been isolated and characterized, including 1724 bp of the 5'-flanking region. The CELL gene, which most likely is a psuedogene, spans 4846 bp, and due to the absence of a 4.8-kb segment, the CEL gene exons 2-7 are not present in the CELL gene. Despite these differences, the CELL gene is transcribed. We have also assigned the CELL gene to a separate locus at chromosome 9q34-qter. PMID- 1639391 TI - Cloning of six new genes with zinc finger motifs mapping to short and long arms of human acrocentric chromosome 22 (p and q11.2). AB - Zinc finger genes encode proteins containing tandemly repeated zinc-mediated folded structures that are found in several transcriptional regulatory proteins. To identify new zinc finger genes, we have screened at low stringency human cosmid libraries enriched in chromosome 22 sequences with a probe derived from the finger region of the mouse Kruppel-like gene, mKr2. We identified 23 nonoverlapping human cosmids cross-hybridizing with the probe. All sequences obtained from cosmid subclones hybridizing with the probe revealed Kruppel-type consensus sequences. Hybridizations to somatic cell hybrid panels and to metaphase chromosomes revealed that 2 nonoverlapping zinc finger cosmids map to chromosome 22p and 4 map to 22q11.2. The 17 other nonoverlapping cosmids most likely map to other chromosomes. The short arms of acrocentric chromosomes are thought to encode only ribosomal RNA genes. Therefore, the identification of two zinc finger genes on chromosome 22p represents an unexpected finding of unknown significance. The four zinc finger genes that map to 22q11.2 are within the cat eye and DiGeorge syndrome regions and thus provide us with potential candidate genes for these developmental malformations. PMID- 1639392 TI - A missense mutation (Asp250----Asn) in exon 6 of the human lipoprotein lipase gene causes chylomicronemia in patients of different ancestries. AB - We have previously reported two common lipoprotein lipase (LPL) gene mutations underlying LPL deficiency in the majority of 37 French Canadians (Monsalve et al., 1990. J. Clin. Invest. 86: 728-734; Ma et al., 1991. N. Engl. J. Med. 324: 1761-1766). By examining the 10 coding exons of the LPL gene in another French Canadian patient, we have identified a third missense mutation that is found in two of the three remaining patients for whom mutations are undefined. This is a G to A transition in exon 6 that results in a substitution of asparagine for aspartic acid at residue 250. Using in vitro site-directed mutagenesis, we have confirmed that this mutation causes a catalytically defective LPL protein. In addition, the Asp250----Asn mutation was also found on the same haplotype in an LPL-deficient patient of Dutch ancestry, suggesting a common origin. This mutation alters a TaqI restriction site in exon 6 and will allow for rapid screening in patients with LPL deficiency. PMID- 1639393 TI - Characterization and chromosomal mapping of the gene encoding the cellular DNA binding protein HTLF. AB - A region of the human T-cell leukemia virus long terminal repeat (HTLV-I LTR) located between -155 and -117 is important in the regulation of gene expression by the ets family of transcription factors. In an attempt to identify additional cellular transcription factors that bind to this portion of the HTLV-I LTR, we used lambda gt11 expression cloning with oligonucleotides corresponding to this element. A 1239-bp cDNA was isolated from a Jurkat cDNA library, which encoded a protein capable of binding to this purine-rich region. This protein, which we designated human T-cell leukemia virus enhancer factor (HTLF), contains a domain with homology to the recently described fork head DNA binding domain. Chromosome mapping of the HTLF gene demonstrated that it was localized to human chromosome 2p16-p22. HTLF is a unique cellular gene that may function in the transcriptional regulation of HTLV-I LTR. PMID- 1639394 TI - A yeast artificial chromosome contig encompassing the type 1 neurofibromatosis gene. AB - The yeast artificial chromosome (YAC) system (Burke et al., 1987, Science 236: 806-812) allows the direct cloning of large regions of the genome. A YAC contig map of approximately 700 kb encompassing the region surrounding the type 1 neurofibromatosis (NF1) locus on 17q11.2 has been constructed. A single YAC containing the entire NF1 locus has been constructed by homologous recombination in yeast. In the process of contig construction a novel method of YAC end rescue has been developed by YAC circularization in yeast and plasmid rescue in bacteria. YACs containing homology to the NF1 region but mapping to another chromosome have also been discovered. Sequences of portions of the homologous locus indicate that this other locus is a nonprocessed pseudogene. PMID- 1639395 TI - North Carolina macular dystrophy is assigned to chromosome 6. AB - North Carolina macular dystrophy (NCMD) is an autosomal dominant macular dystrophy causing impaired central vision at an early age, is completely penetrant, and is present in a single large family. With the development of the hypervariable microsatellite (CA repeats) markers in the human genome, it was possible to relatively rapidly screen most of the genome for linkage to the NCMD gene. After utilizing 124 genetic markers, which excluded over 95% of the human genome, three Marshfield microsatellites located at 6q13-q21 were linked to the NCMD locus. Marshfield marker (MFD) 131 gave a lod score of Z(theta) = 4.36 at theta = 0.137; MFD 171 gave a Z(theta) = 8.42 at theta = 0.004; and MFD 97 gave a Z(theta) = 13.10 at theta = 0.017. Other retinal diseases have been reported on 6q stressing the importance of this region and possibly suggesting that these diseases may be allelic or located in part of a large macular gene family. Locating and characterizing the NCMD gene may be an important step in understanding this group of maculopathies as well as age-related macular degeneration (AMD), a common cause of blindness in the elderly. PMID- 1639396 TI - A single serine:pyruvate aminotransferase gene on rat chromosome 9q34-q36. AB - It was found in our previous study (Oda et al., 1990. J. Biol. Chem. 265: 7513 7519) that in the rat two mRNAs encoding mitochondrial and peroxisomal serine:pyruvate aminotransferase (SPT/AGT) are formed from a single SPT/AGT gene through alternative transcription initiation in exon 1. In an attempt to analyze the mechanisms underlying this unique phenomenon, we have isolated genomic clones harboring the entire rat SPT/AGT gene. In the present study, the location of the rat SPT/AGT gene was determined to be in the q34-q36 region of chromosome 9 by fluorescence in situ hybridization. Southern blot analysis of rat genomic DNA revealed an allelic BamHI restriction fragment length polymorphism among three different inbred rat strains. These results indicated that a single copy SPT/AGT gene is located on chromosome 9q34-q36 in the rat genome. This locus has been assigned the gene symbol Spat. PMID- 1639397 TI - Ordering of human chromosome 3p markers by radiation hybrid mapping. AB - To construct a panel of radiation hybrids (RHs) for human chromosome 3p mapping, mouse microcell hybrid cells, A9(neo3/t)-5, containing a single copy of human chromosome 3p with pSV2neo plasmid DNA integrated at 3p21-p22 were irradiated and fused to mouse A9 cells. A panel of 96 RHs that retain several sizes and portions of human chromosome 3p segments was used to map 25 DNA markers for chromosome 3p. Eight of them, H28, H29, H32, H33, H35, H38, H48, and H64, were cloned from Alu primed PCR products using A9(neo3/t)-5 cell DNA as a template. The most likely order of the 24 markers, except for H28, based on the statistical ordering method proposed by Falk, was cen-D3S4-D3S3-D3S30-H29-D3S13-D3S2-+ ++H48-D3F15S2-D3S32 D3S23-CCK-H35-H33- D3S11-D3S12-RARB-THRB(ERBA2-pBH302)- H64-H38-RAF1-D3S18-H32 D3S22-pter. The order and location of these markers were in good agreement with those previously determined by other mapping methods, suggesting that a panel of these 96 RHs is a valuable source for a rapid mapping of human chromosome 3p markers. PMID- 1639398 TI - Gene-centromere linkage mapping by PCR analysis of individual oocytes. AB - We describe a general method of determining the recombination fraction between a polymorphic locus and the centromere in any species where single oocytes can be obtained. After removal of the first polar body, each oocyte is analyzed by PCR. The frequency of oocytes heterozygous at the polymorphic locus is used to estimate the recombination fraction. We estimate a recombination fraction of 0.15 between the mouse major histocompatibility complex (H-2) and the centromere of chromosome 17. PMID- 1639399 TI - Degenerate oligonucleotide-primed PCR: general amplification of target DNA by a single degenerate primer. AB - A version of the polymerase chain reaction (PCR), termed degenerate oligonucleotide-primed PCR (DOP-PCR), which employs oligonucleotides of partially degenerate sequence, has been developed for genome mapping studies. This degeneracy, together with a PCR protocol utilizing a low initial annealing temperature, ensures priming from multiple (e.g., approximately 10(6) in human) evenly dispersed sites within a given genome. Furthermore, as efficient amplification is achieved from the genomes of all species tested using the same primer, the method appears to be species-independent. Thus, for the general amplification of target DNA, DOP-PCR has advantages over interspersed repetitive sequence PCR (IRS-PCR), which relies on the appropriate positioning of species specific repeat elements. In conjunction with chromosome flow sorting, DOP-PCR has been applied to the characterization of abnormal chromosomes and also to the cloning of new markers for specific chromosome regions. DOP-PCR therefore represents a rapid, efficient, and species-independent technique for general DNA amplification. PMID- 1639400 TI - YAC mapping by FISH using Alu-PCR-generated probes. AB - Human genomic mapping has been greatly advanced by the independent development of three new methods: large DNA fragment cloning in yeast artificial chromosomes, amplification from complex DNAs of human specific segments by Alu-PCR, and high resolution localization of complex DNA probes by fluorescent in situ hybridization. We describe here the combination of these three analytical tools for efficient and accurate localization of randomly screened or especially selected human YAC recombinants to chromosome 11. We map a YAC clone encompassing the pepsinogen A (PGA) locus to 11q13.1-11q13.3. PMID- 1639401 TI - Construction, analysis, and application of a radiation hybrid mapping panel surrounding the mouse agouti locus. AB - The region surrounding the agouti coat color locus on mouse Chromosome 2 contains several genes required for peri-implantation development, limb morphogenesis, and segmentation of the nervous system. We have applied radiation hybrid mapping, a somatic cell genetic technique for constructing long-range maps of mammalian chromosomes, to eight molecular markers in this region. Using a mathematical model to estimate the frequency of radiation-induced breakage, we have constructed a map that spans approximately 20 recombination units and 475 centirays8000. The predicted order of markers, Prn-p-Pygb-Emv-13-Psp-Xmv-10-Emv 15-Src-Ada, is consistent with a previously derived multipoint meiotic map for six of the eight markers and suggests that Xmv-10 may lie relatively close to one or more of the agouti recessive lethal mutations. The resolution of our map is approximately 40-fold higher than the meiotic map, but the median retention frequency of mouse DNA in hybrid cells, 0.12, is 4-fold lower than similar experiments with human chromosomes. From one of the radiation hybrid lines that contained a minimum amount of mouse DNA, 25 independent cosmids were isolated with a mouse-specific hybridization probe. Single-copy fragments from two of these cosmids were shown to originate from mouse Chromosome 2, and the meiotic map position of one was found to be within 10 recombination units of the region of interest. Our results indicate more precise map positions for Pygb and Xmv-10, demonstrate that radiation hybrid mapping can provide high-resolution map information for the mouse genome, and establish a new method for isolating large fragments of DNA from a specific subchromosomal region. PMID- 1639402 TI - The beta globin gene cluster of the prosimian primate Galago crassicaudatus: nucleotide sequence determination of the 41-kb cluster and comparative sequence analyses. AB - The nucleotide sequence of the beta globin gene cluster of the prosimian Galago crassicaudatus has been determined. A total sequence spanning 41,101 bp contains and links together previously published sequences of the five galago beta-like globin genes (5'-epsilon-gamma-psi eta-delta-beta-3'). A computer-aided search for middle interspersed repetitive sequences identified 10 LINE (L1) elements, including a 5' truncated repeat that is orthologous to the full-length L1 element found in the human epsilon-gamma intergenic region. SINE elements that were identified included one Alu type I repeat, four Alu type II repeats, and two methionine tRNA-derived Monomer (type III) elements. Alu type II and Monomer sequences are unique to the galago genome. Structural analyses of the cluster sequence reveals that it is relatively A+T rich (about 62%) and regions with high G+C content are associated primarily with globin coding regions. Comparative analyses with the beta globin cluster sequences of human, rabbit, and mouse reveal extensive sequence homologies in their genic regions, but only human, galago, and rabbit sequences share extensive intergenic sequence homologies. Divergence analyses of aligned intergenic and flanking sequences from orthologous human, galago, and rabbit sequences show a gradation in the rate of nucleotide sequence evolution along the cluster where sequences 5' of the epsilon globin gene region show the least sequence divergence and sequences just 5' of the beta globin gene region show the greatest sequence divergence. PMID- 1639403 TI - Molecular mapping of mouse chromosomes 4 and 6: use of a flow-sorted Robertsonian chromosome. AB - The development of dense genetic maps of mammalian chromosomes is facilitated when chromosome-specific libraries are used as a source of genetic markers. To saturate the genetic maps of mouse chromosomes 4 and 6, we have made use of fluorescent-activated chromosome sorting to purify a 4:6 Robertsonian chromosome from a cell line harboring the Rb(4:6)2Bnr translocation. After staining with chromomycin A3 and Hoechst 33528, this chromosome was separated from the other mouse chromosomes. DNA was isolated from the fraction containing the Robertsonian chromosome and subcloned into the insertion vector lambda gt10, generating a library with 4.6 x 10(5) independent phage. A total of 19 single-copy sequences were used to type the progeny of a C57BL/6J x Mus spretus backcross that had previously been typed for loci on chromosomes 4 and 6. Approximately 70% of the clones in the library mapped to either chromosome 4 or 6 as assessed by genetic mapping and by use of a somatic cell hybrid panel. Simple sequence repeats have also been isolated from this library. Further characterization of these microsatellites should accelerate efforts to map mouse chromosomes 4 and 6 using PCR. In addition, flow sorting of Robertsonian chromosomes suggests a general approach for making chromosome-specific libraries in mouse. PMID- 1639404 TI - Nucleotide sequence analysis of human hypoxanthine phosphoribosyltransferase (HPRT) gene deletions. AB - We have determined the nucleotide sequences of 10 intragenic human HPRT gene deletion junctions isolated from thioguanine-resistant PSV811 Werner syndrome fibroblasts or from HL60 myeloid leukemia cells. Deletion junctions were located by fine structure blot hybridization mapping and then amplified with flanking oligonucleotide primer pairs for DNA sequence analysis. The junction region sequences from these 10 HPRT mutants contained 13 deletions ranging in size from 57 bp to 19.3 kb. Three DNA inversions of 711, 368, and 20 bp were associated with tandem deletions in two mutants. Each mutant contained the deletion of one or more HPRT exon, thus explaining the thioguanine-resistant cellular phenotype. Deletion junction and donor nucleotide sequence alignments suggest that all of these HPRT gene rearrangements were generated by the nonhomologous recombination of donor DNA duplexes that share little nucleotide sequence identity. This result is surprising, given the potential for homologous recombination between copies of repeated DNA sequences that constitute approximately a third of the human HPRT locus. No difference in deletion structure or complexity was observed between deletions isolated from Werner syndrome or from HL60 mutants. This suggests that the Werner syndrome deletion mutator uses deletion mutagenesis pathway(s) that are similar or identical to those used in other human somatic cells. PMID- 1639405 TI - Molecular structure and genetic stability of human hypoxanthine phosphoribosyltransferase (HPRT) gene duplications. AB - We have determined the genetic stability of three independent intragenic human HPRT gene duplications and the structure of each duplication at the nucleotide sequence level. Two of the duplications were isolated as spontaneous mutations from the HL60 human myeloid leukemia cell line, while the third was originally identified in a Lesch-Nyhan patient. All three duplications are genetically unstable and have a reversion rate approximately 100-fold higher than the rate of duplication formation. The molecular structures of these duplications are similar, with direct duplication of HPRT exons 2 and 3 and of 6.8 kb (HL60 duplications) or 13.7 kb (Lesch-Nyhan duplication) of surrounding HPRT sequence. Nucleotide sequence analyses of duplication junctions revealed that the HL60 derived duplications were generated by unequal homologous recombination between clusters of Alu repeats contained in HPRT introns 1 and 3, while the Lesch-Nyhan duplication was generated by the nonhomologous insertion of duplicated HPRT DNA into HPRT intron 1. These results suggest that duplication substrates of different lengths can be generated from the human HPRT exon 2-3 region and can undergo either homologous or nonhomologous recombination with the HPRT locus to form gene duplications. PMID- 1639406 TI - Mapping of the motor neuron degeneration (Mnd) gene, a mouse model of amyotrophic lateral sclerosis (ALS). AB - The motor neuron degeneration mutation (Mnd) causes a late-onset, progressive degeneration of upper and lower motor neurons in mice. After establishing genetic and environmental conditions that distinguish the phenotypes of Mnd/Mnd from +/Mnd mice, Mnd was mapped to proximal Chr 8, using endogenous retroviruses as markers. The map location was confirmed with additional linked polymorphic markers. The outcross/intercross matings to the strain AKR/J, which were used to follow the segregation of the retroviral markers with respect to Mnd, also revealed the existence of a timing effect. Approximately one-fourth of the affected Mnd/Mnd F2 progeny showed accelerated disease. The Mnd mouse model should allow study of mechanisms affecting onset and progression of specific neuronal degeneration in both animal and human neurological disease. PMID- 1639407 TI - Colocalization of the genes for the alpha 3(IV) and alpha 4(IV) chains of type IV collagen to chromosome 2 bands q35-q37. AB - Each type of basement membrane in man contains between two and five genetically distinct type IV collagens: alpha 1(IV)-alpha 5(IV). Genes for alpha 1(IV), alpha 2(IV), alpha 3(IV), and alpha 5(IV) have been isolated. We have recently isolated partial cDNAs for the fifth member of the family, designated alpha 4(IV). On the basis of comparison of the deduced peptide sequences of all five chains, the type IV collagens can be divided into two families: alpha 1-like, comprising alpha 1(IV), alpha 3(IV), and alpha 5(IV); and alpha 2-like, comprising alpha 2(IV) and alpha 4(IV). Genes encoding the alpha 1(IV) and alpha 2(IV) chains (COL4A1 and COL4A2) both map to human chromosome 13q34 and have been shown to be transcribed from opposite DNA strands using a common bidirectional promoter that allows coordinate regulation of the two chains. Indeed, these two chains are commonly found together in basement membrane and form [alpha 1]2.[alpha 2] heterotrimers. Whereas alpha 1(IV) and alpha 2(IV) have been found in all basement membranes studied hitherto, it has been shown that alpha 3(IV) and alpha 4(IV) are found in only a subset of basement membranes. In basement membranes where either of these molecules is present, however, they are found together. In view of this relationship and the structural similarities between alpha 1(IV) and alpha 3(IV) and between alpha 2(IV) and alpha 4(IV), we hypothesized that COL4A3 and COL4A4, the genes encoding alpha 3(IV) and alpha 4(IV), respectively, have a genomic organization similar to that of COL4A1 and COL4A2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639408 TI - Fluorescence in situ hybridization of YAC clones after Alu-PCR amplification. AB - Alu-PCR protocols were optimized for the generation of human DNA probes from yeast strains containing yeast artificial chromosomes (YACs) with human inserts between 100 and 800 kb in size. The resulting DNA probes were used in chromosome in situ suppression (CISS) hybridization experiments. Strong fluorescent signals on both chromatids indicated the localization of specific YAC clones, while two clearly distinguishable signals were observed in greater than or equal to 90% of diploid nuclei. Signal intensities were generally comparable to those observed using chromosome-specific alphoid DNA probes. This approach will facilitate the rapid mapping of YAC clones and their use in chromosome analysis at all stages of the cell cycle. PMID- 1639409 TI - Refinement of diagnostic assays for a probable causal mutation for porcine and human malignant hyperthermia. AB - The substitutions of T for C1843 in the porcine ryanodine receptor (RYR1) gene, which deletes a HinPI restriction endonuclease site and creates a HgiAI site, and of T for C1840 in human RYR1, which deletes a RsaI site, lead to Cys for Arg substitutions in the ryanodine receptors and are probable causal mutations for malignant hyperthermia (MH). To improve the restriction endonuclease assay of these sites, thereby providing an accurate, reliable diagnosis for MH, introns flanking the exon containing the mutation were sequenced, permitting identification and PCR amplification of a 659-bp porcine gene sequence that contains both constant and variant HgiAI sites and a 922-bp human gene sequence that contains both constant and variant RsaI sites. As a result, these PCR amplified sequences contain constant internal controls for the reliable differentiation by restriction endonuclease digestion of normal, heterozygous, and MH genotypes. PMID- 1639410 TI - XY sex reversal associated with a nonsense mutation in SRY. AB - Sex determination in humans is mediated through the expression of a testis determining gene on the Y chromosome. In humans, a candidate gene for the testis determining factor (TDF) that encodes a protein with a putative DNA-binding motif and has been isolated is termed SRY. Here we describe an XY sex-reversed female with pure gonadal dysgenesis who harbors a de novo nonsense mutation in the SRY open reading frame (SRY-orf). This single-basepair substitution results directly in the formation of a termination codon in the putative SRY DNA-binding motif, presumably leading to a nonfunctional gene product. This brings the number of reported XY sex-reversed females with de novo mutations in the known SRY-orf to three, each occurring in the putative DNA-binding domain. This provides further evidence to support SRY being TDF in humans and also indicates the functional importance of the putative DNA-binding domain of the SRY protein. PMID- 1639411 TI - A radiation-reduced hybrid cell line containing 5 Mb/17 cM of human DNA from 9q34. AB - Disease gene loci for tuberous sclerosis (TSC1), idiopathic torsion dystonia (DYT1), and nail-patella syndrome (NPS1) have been mapped by genetic linkage analysis to human chromosome 9q band 34. To create a resource for physical mapping and manipulation of this region of the genome, we have created a radiation-reduced hybrid cell line containing DNA from human 9q34 as its only human component. This cell line, E6B, has been characterized by Southern blot and PCR analysis using a panel of 9q markers and fluorescent in situ hybridization. We estimate that it contains 5 Mb of human DNA, equal to 17 cM of genetic distance, extending from AK1 to ABO on 9q34. PMID- 1639412 TI - A cluster of expressed zinc finger protein genes in the pericentromeric region of human chromosome 10. AB - Three members of the human zinc finger Kruppel family, ZNF11/KOX2, ZNF22/KOX15, and ZNF25/KOX19, have been regionally localized to the pericentromeric region of chromosome 10 by in situ chromosomal hybridization and somatic cell hybrid analysis. ZNF25/KOX19 is located centromeric to a breakpoint in chromosome band 10q11.2 in the chromosome region 10p11.2-q11.2, whereas ZNF22/KOX15 maps distal to it in band 10q11.2. Sequences hybridizing to the KOX2 probe are found at two loci, ZNF11A and ZNF11B, that map proximal and distal to the 10q11.2 breakpoint, respectively. The two ZNF11 loci probably represent two related sequences in 10p11.2-q11.2. This cluster of ZNF/KOX genes is of particular interest since the loci for multiple endocrine neoplasia type 2A and 2B (MEN2A and MEN2B) syndromes have been assigned to this region by linkage analysis. PMID- 1639413 TI - MAF45, a highly polymorphic marker for the pseudoautosomal region of the sheep genome, is not linked to the FecXI (Inverdale) gene. AB - A highly polymorphic dinucleotide repeat, or microsatellite, that shows partial sex-linked inheritance in sheep has been isolated from the sheep genome. Our data indicate that the locus is in the pseudoautosomal region approximately 13 cm from the boundary with the sex-linked regions. The locus, designated MAF45, has 12 alleles with a PIC of 0.84. The same primers amplify a single polymorphic locus in cattle and goats. This locus was not linked to the Inverdale gene, an X-linked gene that increases the ovulation rate in sheep. PMID- 1639414 TI - The Machado-Joseph disease locus is different from the spinocerebellar ataxia locus (SCA1). AB - Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative spinocerebellar ataxia that has been described primarily in families of Azorean or Portuguese descent. MJD and chromosome 6p-linked spinocerebellar ataxia (SCA1) are difficult to differentiate clinically, and it has been suggested that they may be allelic variants of the same disorder. We have tested MJD families for linkage to six DNA sequence polymorphisms located on chromosome 6p, including the highly informative dinucleotide repeat, D6S89. Seventeen centimorgans telomeric to and 41 cM centromeric to D6S89, a region that includes the SCA1 locus reported to be within 3 cM of D6S89, have been excluded. These data provide conclusive evidence that MJD and SCA1 are nonallelic. PMID- 1639415 TI - Sequence of the human factor VIII-associated gene is conserved in mouse. AB - cDNA and genomic clones corresponding to the human factor VIII-associated gene (F8A) were isolated from mouse cDNA and F8A-enriched genomic libraries. The sequences of these clones revealed an intronless gene coding for 380 amino acids, with 85% identity to the predicted human sequence. The single murine gene copy is genetically linked to factor VIII, but appears to lie outside the factor VIII gene by physical mapping. Like the human gene, the mouse F8A gene is highly expressed in a wide variety of tissues. This evolutionary comparison has helped to clarify the derived amino acid sequence in the human and strongly supports the hypothesis that the F8A gene encodes a protein. PMID- 1639416 TI - Chromosomal localization of an SH2-containing tyrosine phosphatase (PTPN6). AB - We have used panels of somatic cell hybrids and fluorescent in situ hybridization to determine the chromosomal localization of the novel nontransmembrane tyrosine phosphatase PTPN6 (protein tyrosine phosphatase, nonreceptor type 6), which contains two SH2 domains. PTPN6 maps to 12p13, a region commonly involved in leukemia-associated chromosomal abnormalities. Since PTPN6 is expressed at high levels in hematopoietic cells of all lineages and its expression is induced early in hematopoietic differentiation, altered expression and/or structure of PTPN6 may play a role in leukemogenesis. PMID- 1639417 TI - Expressed sequence tags and chromosomal localization of cDNA clones from a subtracted retinal pigment epithelium library. AB - Expressed sequence tags (ESTs) provide useful molecular landmarks for physical mapping and identify the position of an expressed region in the genome. The use of subtracted cDNA libraries enriched for tissue-specific genes as a source of ESTs should reduce the repetitive isolation of constitutively expressed sequences. We report here the sequence tags from the 3'-end region of 58 new directionally cloned cDNAs from a subtracted human retinal pigment epithelium (RPE) cell line library. Eight of the cDNAs have been assigned to human chromosomes using PCR-based EST assays. Chromosomal mapping of subtracted RPE cDNA clones may also help in identifying candidate genes for inherited eye diseases. PMID- 1639418 TI - Assignment of the human stromelysin 3 (STMY3) gene to the q11.2 region of chromosome 22. AB - The human stromelysin 3 (STMY3) gene, a new member of the matrix metalloproteinase (MMP) gene family, may contribute to breast cancer cell invasion, and has been localized by in situ hybridization to the long arm of chromosome 22. As demonstrated using a panel of somatic cell hybrids, the STMY3 gene is in band 22q11.2, in close proximity to the BCR gene involved in chronic myeloid leukemia, but far from the (11;22) translocation breakpoint observed in Ewing sarcoma. This position differs from that reported on chromosomes 11 and 16 for the other MMP genes, suggesting that stromelysin 3 could be a member of a new MMP subfamily. PMID- 1639419 TI - Synteny between the loci for a novel FACIT-like collagen locus (D6S228E) and alpha 1 (IX) collagen (COL9A1) on 6q12-q14 in humans. AB - A 1.8-kb cDNA encoding portion of a novel collagenous chain was isolated from a human rhabdomyosarcoma cell line by cross-hybridization using a chicken type V collagen probe. Sequence analysis suggests that this chain belongs to the recently discovered group of collagens, termed the FACIT class of macromolecules. This cDNA was used to locate the corresponding gene (D6S228E) to chromosome 6, notably at position 6q12-q14. Interestingly, within this region of human chromosome 6 residues the alpha 1 (IX) collagen gene (COL9A1), a member of the FACIT group. PMID- 1639421 TI - CpG suppression in vertebrate genomes does not account for the rarity of (CpG)n microsatellite repeats. AB - Simple microsatellite repetitive sequences are widely distributed in eukaryotic genomes. Using the GCG Find program, the distribution of each type of mono- and dinucleotide repetitive sequence has been examined in GenBank sequences. Examples of each type of simple satellite sequence could be found, although the frequency of (CpG)n greater than or equal to 8 repeats was extremely low. The suppression of CpG dinucleotides in vertebrates does not adequately explain the rarity of this repeat since (CpG)n repeats are also extremely infrequent in species genomes where CpG dinucleotides are not suppressed. Instead, it is proposed that (CpG)n repeats must possess a DNA conformation that has a deleterious structural effect. PMID- 1639420 TI - Gene-dosage mapping of 30 DNA markers on chromosome 21. AB - Using a slot-blot method for the dosage of single-copy sequences, the copy numbers of 30 chromosome 21 markers were assessed in the blood DNA of 11 patients with partial trisomy or monosomy 21 and in the DNA of a patient-derived human hamster hybrid cell line carrying a microduplication of chromosome 21. The physical order of these markers on chromosome 21 was thereby determined. PMID- 1639422 TI - Sequence analysis of a partial deletion of the human steroid sulfatase gene reveals 3 bp of homology at deletion breakpoints. AB - The majority of patients with steroid sulfatase deficiency have a deletion of the entire STS gene located on the distal short arm of the human X chromosome; however, two patients with partial gene deletions have been identified. We now report the sequences at the breakpoints of a deletion of the 3' end of the STS gene. The deletion starts within intron 7 of the gene and extends over 150 kb downstream toward the centromere. Analysis of sequences flanking the deletion breakpoints revealed 3 bp of homology. The 3' flanking sequence provides a new probe for isolation of YAC clones and for studying patients with deletions in this region of the X chromosome. PMID- 1639423 TI - Identification of three novel missense PKU mutations among Chinese. AB - Three novel missense mutations have been identified in the phenylalanine hydroxylase (PAH) genes of Chinese individuals afflicted with various degrees of phenylketonuria (PKU). A T-to-C transition was observed in exon 5 of the gene, resulting in the substitution of Phe161 by Ser161. Two substitutions, G-to-T and T-to-G, were observed in exon 7, resulting in the substitution of Gly247 by Val247 and Leu255 by Val255, respectively. Expression analysis demonstrated that these mutant proteins produced between 0 and 15% of normal PAH enzyme activity. Population screening of a Chinese sample population indicates that these mutations are quite rare, together accounting for only about 4% of all PKU alleles among the Chinese. The P161S and G247V mutations were each present on a single PAH RFLP haplotype 4 chromosome in patients form Northern China, while the L255V mutation was present on chromosomes of both haplotypes 18 and 21 in patients from Southern China. These results suggest that the remaining 30% of uncharacterized PKU alleles in the Chinese population may bear a large number of relatively rare PAH mutations. PMID- 1639424 TI - Characterization of a highly polymorphic region near the first exon of the human MAOA gene containing a GT dinucleotide and a novel VNTR motif. AB - The genes encoding the A and B forms of the human monoamine oxidase enzymes (MAOA and MAOB) are localized at Xp11.23-Xp11.4. We report the characterization of a highly informative polymorphic region within a 2.9-kb cloned fragment containing the first exon of the MAOA gene. The polymorphic region consists of a GT microsatellite directly adjacent to an imperfectly duplicated novel 23-bp VNTR motif. DNA sequencing within and flanking the repeated segment allowed the design of specific amplification primers. In 56 unrelated females, 15 different alleles were identified with sizes ranging from 285 to 388 bp. The alleles differed in both the number of dinucleotide and the number of VNTR repeats, yielding a highly informative polymorphic marker locus with a calculated heterozygosity value of 75%. PMID- 1639425 TI - Mapping of two chromosome 15 microsatellites. PMID- 1639426 TI - Regional localization of the gene for cardiac muscle actin (ACTC) on chromosome 15q. PMID- 1639427 TI - The gene for receptor-linked protein-tyrosine-phosphatase (PTPA) is assigned to human chromosome 20p12-pter by in situ hybridization (ISH and FISH). PMID- 1639428 TI - Localization of a bile acid UDP-glucuronosyltransferase gene (UGT2B) to chromosome 4 using the polymerase chain reaction. PMID- 1639429 TI - Detection of mutations in the factor VIII gene using single-stranded conformational polymorphism (SSCP). PMID- 1639430 TI - Beneficial effects of endotoxin treatment on metabolism in tumour-bearing rats. AB - The effects of endotoxin treatment on host metabolism in tumour-bearing rats were investigated. Metabolism in control rats (non-tumour-bearing) was slightly altered by endotoxin treatment, whereas in tumour-bearing rats a number of biochemical parameters that were initially perturbed by the presence of the tumour had returned to normal at 48 h post-treatment. The beneficial effects included increased blood glucose and insulin concentrations, and decreased ketone body, triglyceride and lactate concentrations. Potentially non-beneficial effects of endotoxin observed in both tumour-bearing and control rats included decreased plasma cholesterol, and increased plasma phosphate, potassium and alkaline phosphatase levels. Endotoxin caused haemorrhaging in the encapsulated tumour, and this was associated with histological evidence of endothelial damage, red cell infiltration into surrounding tumour tissue and a marked decrease in cell viability. The in vivo uptake of glucose by the tumour, measured by 2-deoxy [U 14C]glucose uptake, was decreased by 96% following endotoxin treatment, and this was associated with a two-fold increase in glucose uptake by muscle. It is concluded that endotoxin treatment has major effects on cell viability and the integrity of vasculature in the tumour, which limits glucose uptake by the tumour and thereby decreases the energy and substrate requirements of the tumour, thus benefiting the host. It is suggested that tumour cytotoxicity and intra-tumour haemorrhage are the result of endotoxin stimulating cytokine release from macrophages that are already activated by the presence of the tumour.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639431 TI - Increased release of interleukin-1 and tumour necrosis factor by interleukin-2 induced lymphokine-activated killer cells in the presence of cisplatin and FK 565. AB - The supernatants of peripheral blood lymphocytes cultured in interleukin-2 (IL-2) for 4 days contained tumour necrosis factor (TNF) and interleukin-1 (IL-1). Addition of cisplatin (CP) or FK-565 to these cultures increased the level of both of these cytokines in culture supernatants. Furthermore, when the LAK cells induced by culture with IL-2 in the presence or absence of CP/FK-565 were co cultured with tumour cells, the production of these cytokines was significantly enhanced. The level of enhancement depended on the ratio of LAK cells to tumour cells used and the length of coincubation of the two cell types. Culture supernatants of LAK cells and LAK cells stimulated by tumour cells were also cytotoxic to MCF-7 and U937 cells in 72 h cytotoxic assay, and antibodies specific for TNF and IL-1 inhibited the supernatant-mediated cytotoxicity. These results suggest that, in addition to the up-regulation of IL-2-induced LAK activity, treatment of PBL with CP/FK-565 leads to enhanced production of various cytokines with potential antitumour and immunoregulatory activity. PMID- 1639432 TI - Lymphoid tissue in rat oral mucosa: structure and function. AB - Lymphocyte and macrophage/dendritic cell populations in the oral cavity of the rat were studied by immunohistochemistry. Furthermore, the reactivity of the oral mucosa towards antigen and its position in the mucosal immune system was investigated by staining antibody-forming cells and comparing serum and saliva antibody titres. Although numerous lymphocytes and non-lymphoid cells were present in the oral mucosa, organized lymphoid tissue could not be found. The majority of the lymphocytes are T cells, particularly of the T-helper phenotype. Macrophages were found only in the connective tissue, whereas dendritic cells also occurred in the epithelium. The possible functions of the cells in the different sites of the oral mucosa are discussed. Antibody-forming cells were mainly detected in the draining superficial and posterior cervical lymph nodes and in the submandibular glands. The roles of the various compartments of the oral mucosal immune system are discussed with particular reference to the epithelium and connective tissue as induction sites, the draining lymph nodes as sites of proliferation and differentiation, and the submandibular glands as effector sites. PMID- 1639433 TI - Enhanced H2O2 release from immune chicken leucocytes following infection with Eimeria tenella. AB - Cell-mediated immunity is thought to be important in the resistance of chickens to infection by coccidia, and it has been demonstrated that sporozoites of Eimeria tenella are very sensitive to superoxide ions. Therefore an investigation into the cellular responses in naive specific pathogen-free and hyperimmune birds was carried out with particular attention to their ability to produce reactive derivatives of oxygen. Leucocytes were isolated from the blood, spleen and caecal mucosa of chickens infected with E. tenella and assessed for their ability to release H2O2. Leucocytes obtained from the blood and spleen of hyperimmune birds 1 day after challenge showed an elevated ability to produce reactive oxygen intermediates. In contrast, the ability of leucocytes from naive chickens to produce these molecules was transiently depressed after challenge. Prior to challenge, mucosal leucocytes from immune chickens were also able to release heightened levels of H2O2 when compared with cells from naive chickens. PMID- 1639434 TI - A transgenic window on peripheral T cell tolerance. AB - There is convincing evidence for the imposition of self-tolerance by means of the clonal deletion of self-reactive T cells within the thymus. Since not all self components may be encountered there, the question must be asked whether tolerance can occur post-thymically. To test this, we have used transgenic technology to direct expression of a 'non-self' gene, H-2Kb, to the insulin-producing beta cells of the pancreas in mice. These 'RIP-Kb' transgenic mice were specifically tolerant of H-2Kb-bearing skin grafts. To test the fate of potentially reactive H 2Kb-specific T cells in these tolerant mice, the RIP-Kb mice were mated to a second series of transgenic mice with rearranged T cell receptor (TCR) genes encoding an H-2Kb-specific TCR to produce 'double transgenic' offspring. The TCR was detectable by a clonotype-specific antibody. Although there was some evidence of intrathymic deletion of those T cells that expressed the highest density of the H-2Kb-specific TCR, lower density cells were present in the periphery. These may have been either indifferent to the H-2Kb molecule expressed on the beta cells or functionally silenced by it. Further experiments are planned to determine which of these two situations exists. PMID- 1639435 TI - Quantitative analysis of lymphokine expression in vivo and in vitro. AB - Constitutive lymphokine production by cells isolated from mice injected with keyhole limpet haemocyanin (KLH) or from mice undergoing an acute graft vs host reaction (GVHR) was very low, but could be markedly increased by T cell receptor (TCR) ligation. This suggested that in vivo levels of lymphokine production are much lower than those induced by in vitro stimulation. Serum lymphokine titres were consistent with this possibility, and analysis of lymphokine mRNA levels using S1-nuclease protection demonstrated that in vitro-stimulated cells from normal, KLH and GVHR mice all had markedly increased levels of lymphokine transcripts relative to levels found in vivo. A novel method combining limiting dilution analysis with polymerase chain reaction amplification of cDNA was developed that showed that these differences in levels of lymphokine production were due at least in part to differences in the frequencies of lymphokine mRNA containing cells. Studies of the means by which differential lymphokine production is achieved demonstrated that CD4+, CD8+ and cytotoxic T lymphocyte (CTL) clones all express a common, restricted set of lymphokines in response to a defined in vitro stimulus, but that individual in vivo primed cells can express at least seven distinct patterns of lymphokine production. PMID- 1639436 TI - Viral escape from immune recognition: multiple strategies of adenoviruses. AB - Human adenoviruses can cause persistent infections in man. The strategies of C type adenoviruses (types Ad2 and Ad5) to evade immune recognition are many, but all involve single early genetic regions (E3). Gene(s) within E3 have been shown to allow the adenovirus to avert cytokine-mediated apoptosis. Furthermore, the E3 region controls the cytotoxic T cell epitope (a major histocompatibility complex [MHC] class I molecule with an adenovirus-derived peptide) on the cell surface of infected cells. On the one hand the E3 gene product 19 kDa can bind to nascent class I MHC in the endoplasmic reticulum and thus prevent its transport to the cell surface, and on the other hand the E3 region down-regulates the E1a gene product, the immunodominant cytotoxic T cell determinant. PMID- 1639437 TI - Frequency of D8/17 B lymphocyte alloantigen in north Indian patients with rheumatic heart disease. AB - Ninety patients with rheumatic heart disease and 50 age- and sex-matched healthy human volunteers representing a North Indian population were typed for the B cell alloantigen D8/17 using a monoclonal antibody and a single step immunofluorescence technique. This alloantigen was expressed in 66.44% patients with RHD as compared with 14% of the normal population. A high relative risk (RR = 11.13) indicated a strong association of D8/17 B cell alloantigen with rheumatic heart disease. Increase in the frequency of the marker was observed with increasing age up to the fifth decade (40-49 years) in these patients. However, the frequency of this alloantigen, in the present study, in North Indian patients with rheumatic heart disease is lower than that reported in the American population. PMID- 1639438 TI - Possible association of the extended MHC haplotype B44-SC30-DR4 with autism. AB - We previously reported that the complement C4B null allele appears to be associated with infantile autism. Since the C4B null allele is known to be part of the extended or ancestral haplotype [B44-SC30-DR4], we investigated the incidence of [B44-SC30-DR4] in 21 autistic children and their parents. This extended haplotype was increased by almost six-fold in the autistic subjects as compared with healthy controls. Moreover, the total number of extended haplotypes expressed on chromosomes of autistic subjects was significantly increased as compared with those expressed on chromosomes of healthy subjects. We conclude that a gene related to, or included in, the extended major histocompatibility complex may be associated with autism. PMID- 1639439 TI - Possible role of Abb gene in mouse resistance to EL4 metastases. AB - "S" (survivor) mutants were produced in mice for genetic analysis of host resistance to metastatic cancers. S-mutants S-27 and S-31 resist transplantation of lymphoma EL4 of parental C57BL/6J (B6) mice while they accept parental skin grafts. Mutant S-27 also resists formation of spontaneous metastases from intradermally growing EL4 tumor into lymph nodes; mutant S-31 is highly susceptible to EL4 metastases. Another mutant, H-2bm26 (bm26), resists EL4 and rejects B6 skin grafts. Major histocompatibility complex (MHC) class I and class II gene expression was compared in these mutants and normal B6 mice. All three mutants tested, S-27, S-31, and bm26, expressed a low amount of Kb mRNA in organ specific fashion. Mutants bm26 and S-31 expressed a low amount of Abb mRNA and of Ab antigen on their spleen cells. Some oligonucleotide probes designed to hybridize to the second exon of the class II MHC gene Abb did not hybridize with DNA from all three mutants. These findings suggest extensive sequence alterations in the Abb gene in mutants S-27, S-31, and bm26; they also suggest a major role of MHC in the control of host resistance to spontaneous metastases of the EL4 tumor. PMID- 1639440 TI - Screening mouse mutations for resistance to cancer metastasis. AB - To search for host genes for resistance/susceptibility to cancer metastasis, mutation analysis was employed. Ten putative mutants of resistance to lymphoma EL4 and four putative mutants of resistance to sarcoma MCA/77-23 of C57BL/6J (B6) mice were produced. These mutants were designated S (for "survivor") mutants; they do not reject parental strain B6 skin grafts. S-mutants resist moderate tumor cell doses: TD50 values in them were increased by a factor of 12 to 600. Genetic linkage tests showed that five S-mutants were linked to mouse major histocompatibility complex (H-2) and five other S-mutants were not linked to this locus. A group of H-2-linked S-mutants resisting EL4 and a mutant, S-87/2, resisting MCA/77-23 were tested for resistance to spontaneous metastases of the same two tumors, EL4 and MCA/77-23. Two of the mutants, S-31 (lymphoma-resisting) and S-87/2 (sarcoma-resisting), were shown to carry mutations of mouse gene(s) for resistance to tumor metastases. In both of these mutants resistance to the original tumor transplant coexisted with highly increased susceptibility to metastasis. These mutants are a new tool to study genes for resistance to cancer metastasis and of mechanism of resistance controlled by each individual gene. PMID- 1639441 TI - A new approach to HLA-DPB1 typing combining DNA heteroduplex analysis with allele specific amplification and enzyme restriction. AB - Allelic polymorphism of HLA-class II antigens plays a key role in the regulation of the immune response and in transplantation immunity. The allelic diversity of these antigens can now be analyzed at the DNA level after amplification by polymerase chain reaction. In this study we apply a simple technique based on the electrophoretic analysis of DNA heteroduplexes to the typing of HLA-DPB1 alleles. In order to increase its resolution, a group-specific amplification was used which subdivides the 19 HLA-DPB1 alleles in two non-overlapping families. A separate analysis was then performed within each group of alleles. This approach allowed an unequivocal one-step typing of the alleles belonging to group 1 which comprises few alleles of high frequency. Some group 2 alleles require, as a further step, the test with a restriction enzyme. The combination of more than one technique represents, in our opinion, the easiest way to solve the micropolymorphism of class II alleles. We conclude that this method, which is very simple, quick, and accurate and does not require probes, may become the method of choice for HLA-DPB1 typing. PMID- 1639443 TI - Molecular cloning of the Ig-alpha subunit of the human B-cell antigen receptor complex. PMID- 1639442 TI - Hypomethylation of MHC class II Eb gene is associated with expression. AB - Methylation patterns in the major histocompatibility complex (MHC) class II Eb locus have been analyzed in cell lines representative of different cell types; in particular those with phenotypes found at various stages of B cell development. A series of variant B cell lymphoma lines which serves as a model in which to investigate mechanisms regulating class II gene expression in normal peripheral B cells has been examined. Eb methylation patterns have also been determined in various healthy mouse tissues. The pattern of methylation of the Eb locus varies between different cell lines and tissue types such that hypomethylation is associated with gene expression. There appears to be a methylation pattern which is permissive for class II gene expression and which is characteristic of a variety of cell lines, but is lost in cell lines representing terminally differentiated class II nonexpressing plasma cells. Another methylation pattern has been identified which is found in cloned cell lines selected for expression of very high levels of cell surface class II product. The patterns of methylation associated with MHC class II expression involve changes in methylation sites located within the first intron and several kilobase pairs 5' of the promoter, but no changes were observed in the 3' end of the locus. Moreover, the different methylation patterns do not map to the prominent CpG rich cluster located 5' of the Eb promoter and which remains completely methylated regardless of transcriptional status. PMID- 1639444 TI - Hepatic encephalopathy in Saudi Arabia: retrospective analysis of 51 patients. AB - The clinical features, prognostic factors, and outcome of 51 patients with hepatic encephalopathy (HE), were retrospectively reviewed. The mean (+/- SD) age of patients was 47.2 (+/- 14.8) years. Seventy-five percent of patients were males and 73% were Saudi. All identified episodes of hepatic encephalopathy were associated with chronic underlying liver disease and no episode occurred as a result of acute fulminant hepatic failure. Most patients presented in advanced stage of hepatic dysfunction and had one or more precipitating factors. In hospital mortality rate was 41% (21 out of 51 patients). Gastrointestinal tract bleeding, electrolytes imbalance and alkalosis were associated with significantly higher mortality rate. However, unadjusted analysis failed to identify certain base-line independent prognostic factors. PMID- 1639445 TI - AIDS with special reference to pediatric aspect. AB - The article discusses the disease AIDS, and its increasing incidence all over the world. The alarming rise of HIV infection amongst those tested in India is noted. The projection as made by WHO are mentioned. The various modes of transmission of HIV infection and the high risk groups for each mode are identified. Clinical manifestation of an adult case is followed by that of a pediatric patient in whom the infection is mostly transplacental. The risk of TAA amongst children is highlighted as also the difference between adult and pediatric AIDS. Diagnosis of AIDS, its management, prognosis and prevention are mentioned. The similarity between HIV-1, SIV and HIV-2 induced immunodeficiency is recorded. PMID- 1639446 TI - Pararectal duplication. PMID- 1639447 TI - Hereditary spherocytosis: experience of 145 cases. AB - 145 patients were diagnosed to have hereditary spherocytosis (HS) over a period of 25 years. Jaundice (66.9%), fever (65.5%), weakness (44.8%), and abdominal pain (35.8%) were the commonest complaints. 94.5% had splenomegaly (JP-17 cm) and 71.7% had hepatomegaly (JP-6 cm). Spherocytes were detected in the peripheral smears of all patients at presentation on careful examination. 67 patients had been investigated elsewhere and spherocytes missed in 86.6%. Gall stones were seen in 20 of the 54 patients investigated. Family history suggestive of HS was available in only 16.6% of cases, whereas examination and investigations revealed HS in almost all families. Splenectomy was done in all symptomatic patients. In the 39 patients followed up for 1-9 years after splenectomy. PMID- 1639448 TI - Role of vagal and sinoaortic baroreflexes in circulatory adjustments to passive head up tilt. AB - To evaluate the contribution of vagal and sinoaortic baroreflexes in circulatory adjustments anaesthetized rabbits were subjected to 70 degree head up tilt with (i) both reflexes intact; (ii) after elimination of sinoaortic reflexes; (iii) after elimination of vagal reflexes; and (iv) after elimination of both categories of reflexes. The results suggest that vagal mediated baroreflexes from cardiopulmonary baroreceptors contribute significantly in circulatory adjustments to passive head up tilt while sinoaortic baroreflexes play the major role. PMID- 1639449 TI - Hematometrocolpos presenting as pelvic outlet obstruction. PMID- 1639450 TI - Response of canine brain loci to intracerebroventricular thyroxine. AB - The effect of intracerebroventricular T4 on certain hypothalamic i.e., POA and VMN and cortical i.e., HPC and CO loci was investigated by recording their electroencepgraphic activity after chronic implantation of cannulae and bipolar electrodes in ten male dogs. Recordings were made for two hours after the microinjection. The predominant pattern of EEG activity was a synchrony of brain waves in all derivations except for POA where biphasic desynchronization synchronization was observed. Final synchrony suggest refractoriness of these loci to T4 which might be playing a protective role. PMID- 1639451 TI - Ultrasonography versus roentgenography in suspected cases of cholecystolithiasis. AB - The present study was carried out to evaluate the relative merits of ultrasonography and roentgenography in 50 cases of suspected cholecystolithiasis. The accuracy rate with roentgenography (plain X-ray abd, OCG and IVC) in the diagnosis of cholecystolithiasis was 92.5% where as it was 95% with ultrasonography. Oral cholecystography should be done in patients with normal ultrasound examination if the symptoms are strongly suggestive of cholecystolithiasis. PMID- 1639452 TI - Pregnancy in a rudimentary uterine horn. AB - A case of pregnancy reaching term in a rudimentary non-communicating horn of the uterus is presented. The pregnancy resulted in the delivery of a live child by cesarian section. The case is being reported for the rarity with which the foetus survives in this condition. PMID- 1639453 TI - Immuno-modulation by exercise: review. AB - Chronic and exhaustive exercise leads to a decline in mitogen-induced lymphocyte proliferation in-vitro and in-vivo. This is suggestive of decrease in cellular and humoral immunity. Majority of workers are of opinion that exercise-induced immunosuppression is related to the production of glucocorticoids in response to the stress associated with exercise. PMID- 1639454 TI - Regulation of contraction and relaxation in arterial smooth muscle. AB - Intracellular calcium concentration ([Ca2+]i)-dependent activation of myosin light chain kinase and its phosphorylation of the 20-kd light chain of myosin is generally considered the primary mechanism responsible for regulation of contractile force in arterial smooth muscle. However, recent data suggest that the relation between [Ca2+]i and myosin light chain phosphorylation is variable and depends on the form of stimulation. The dependence of myosin phosphorylation on [Ca2+]i has been termed the "[Ca2+]i sensitivity of phosphorylation." The [Ca2+]i sensitivity of phosphorylation is "high" when relatively small increases in [Ca2+]i induce a large increase in myosin phosphorylation. Conversely, the [Ca2+]i sensitivity of phosphorylation is "low" when relatively large increases in [Ca2+]i are required to induce a small increase in myosin phosphorylation. There are two proposed mechanisms for changes in the [Ca2+]i sensitivity of phosphorylation: Ca(2+)-dependent decreases in the [Ca2+]i sensitivity of phosphorylation induced by phosphorylation of myosin light chain kinase by Ca(2+) calmodulin protein kinase II and agonist-dependent increases in the [Ca2+]i sensitivity of phosphorylation by inhibition of a myosin light chain phosphatase. I will review the proposed mechanisms responsible for the regulation of [Ca2+]i and the [Ca2+]i sensitivity of phosphorylation in arterial smooth muscle. PMID- 1639455 TI - 12-Lipoxygenase products modulate calcium signals in vascular smooth muscle cells. AB - Previous studies have shown that inhibition of the lipoxygenase pathway of arachidonic acid metabolism can prevent the development of elevated blood pressure in renin-dependent models of hypertension. Agents that inhibit the lipoxygenase pathway such as phenidone and the flavonoid baicalein can selectively attenuate contractile responses to angiotensin II in vivo as well as in isolated vascular tissue. In the present study, the effects of lipoxygenase inhibitors on pressor-induced changes in cytosolic calcium were examined in cultured rat vascular smooth muscle cells using the fluorescent dye fura-2. Two structurally unrelated lipoxygenase inhibitors, baicalein and 5,8,11 eicosatriynoic acid, attenuated angiotensin II-stimulated increases in cytosolic calcium in both normal and calcium-poor buffer. The addition of 5-, 12-, or 15(S) hydroxyeicosatetraenoic acid alone to the cells had no acute effect on intracellular calcium concentration. However, the addition of 12(S) hydroxyeicosatetraenoic acid but not 5- or 15(S)-hydroxyeicosatetraenoic acid restored the initial calcium response to angiotensin II in vascular smooth muscle cells pretreated with both inhibitors; 5,8,11-eicosatriynoic acid also reduced [Arg8]-vasopressin and endothelin-stimulated increases in intracellular calcium. The attenuation of vasopressor-induced calcium transients by agents that inhibit lipoxygenase may explain their observed hypotensive effects in vivo. Moreover, lipoxygenase products, in particular 12(S)-hydroxyeicosatetraenoic acid, may act as mediators for the intracellular actions of angiotensin II and possibly other pressor hormones in vascular tissue by regulation of intracellular calcium metabolism. PMID- 1639456 TI - Distribution and metabolism of angiotensin I and II in the blood vessel wall. AB - The demonstration of all components of the renin-angiotensin system in vascular tissue has raised questions as to the precise location of the local angiotensin II generation within the vascular wall. We investigated the metabolism of angiotensin I to angiotensin II in the vascular wall in the isolated rabbit thoracic aorta. Angiotensin I (3 x 10(-9) M) applied into the aortic lumen was partially converted to angiotensin II (14% after 60 minutes), but most of the luminal angiotensin I was degraded to peptide fragments or diffused as intact angiotensin I, peptide fragments, or both, into the vessel wall. Incubation studies with [3H]angiotensin I revealed that angiotensin I or angiotensin I fragments mainly diffused into the medial layer of the aorta and to a lesser degree into the adventitia and the endothelium. After removal of the endothelium, angiotensin II generation could no longer be detected. Addition of the angiotensin converting enzyme inhibitor ramiprilat (10(-7) M) to the incubation medium led to a complete blockade of angiotensin II generation by endothelial angiotensin converting enzyme. Our results underline the importance of the endothelium for conversion of angiotensin I to angiotensin II and provide evidence that conversion of angiotensin I to angiotensin II is predominantly achieved by endothelial cells. They also support the concept of an endocrine versus autocrine/paracrine renin-angiotensin system where the endothelium of the vasculature is the critical target site for angiotensin II production by both systems and, thus, the most important site for the actions of angiotensin converting enzyme inhibitors. PMID- 1639457 TI - Tissue renin-angiotensin systems in renal hypertension. AB - Angiotensinogen messenger RNA (mRNA) levels were measured in the brain (hypothalamus, lower brain stem, cerebellum), liver, kidneys, and adrenal glands of rats made hypertensive by ligation of the aorta between the renal arteries. We also measured renin mRNA in the kidneys of these renal hypertensive rats. The early phase of hypertension (day 6) was associated with significant increases in plasma renin activity and levels of circulating angiotensin II. The circulating renin-angiotensin system was not activated in the later phase of hypertension (day 24). Angiotensinogen mRNA levels were elevated in the lower brain stem of hypertensive rats at both stages of hypertension. In contrast, angiotensinogen mRNA levels in the hypothalamus were increased only at day 6 after aortic ligation. Decreased levels of angiotensinogen mRNA were observed in the cerebellum in both the early and later phases of the hypertension. Angiotensinogen mRNA levels in the adrenal gland below the ligature fell in the early phases but rose in the later phases of hypertension. Renin mRNA levels of the ischemic kidney remained elevated at both the early and later phases, whereas in both ischemic and nonischemic kidneys, levels of angiotensinogen mRNA remained below sham values throughout the period of study. These results indicate differential expression of renin-angiotensin system mRNAs in tissues of renal hypertensive rats. The differential changes in the expression of angiotensinogen mRNA over the course of development and maintenance of renal hypertension suggest that factors in addition to angiotensin II are important in modulating the expression of renin-angiotensin system genes. PMID- 1639458 TI - Captopril improves impaired endothelium-dependent vasodilation in hypertensive patients. AB - Animal studies suggest that some angiotensin converting enzyme inhibitors augment endothelium-dependent vasorelaxation. We aimed to determine if captopril augments endothelium-dependent vasodilation in middle-aged hypertensive patients. By using strain-gauge plethysmography, forearm vasodilation evoked with intra-arterial acetylcholine (4, 8, 16, and 24 micrograms/min) or nitroprusside (0.2, 0.4, 0.8, and 1.2 micrograms/min) was examined before and after captopril administration (25 mg per os). Before captopril, forearm vasodilation with acetylcholine was less in hypertensive patients (n = 12) than in age-matched (n = 7) or young (n = 7) normotensive subjects, but forearm vasodilation with nitroprusside did not differ among the three groups. Captopril improved forearm vasodilation in hypertensive patients (n = 7) with acetylcholine but nitroprusside did not. In contrast, nifedipine (10 mg per os) did not alter forearm vasodilation with acetylcholine or nitroprusside in hypertensive patients (n = 5). The decreases in mean blood pressure caused by captopril and nifedipine in hypertensive subjects were comparable. Captopril did not alter forearm vasodilation with acetylcholine or nitroprusside in young normotensive subjects (n = 7). These results suggest that captopril in hypertensive patients may acutely improve impaired endothelium dependent forearm vasodilation that does not result from reduction in blood pressure per se. PMID- 1639459 TI - Effects of chronic angiotensin converting enzyme inhibition on glucose tolerance and insulin sensitivity in essential hypertension. AB - The relation between the renin-angiotensin-aldosterone (RAA) system and carbohydrate metabolism and insulin sensitivity in essential hypertension has not been investigated systematically. Twenty nondiabetic patients (age, 49 +/- 1 years; body mass index (BMI), 26.1 +/- 0.4 kg/m2) with essential hypertension (blood pressure, 155 +/- 3/105 +/- 1 mm Hg) received an oral glucose tolerance test (OGTT) at the end of a 1-month placebo period and again monthly during 3 months of angiotensin converting enzyme (ACE) inhibition (cilazapril, 5 mg/day). Furthermore, a two-step euglycemic insulin clamp was performed after placebo and again at the end of treatment. Blood pressure fell by 7 +/- 4/10 +/- 3 mm Hg (p less than 0.001), while BMI remained stable. On the euglycemic clamp, insulin mediated (plasma insulin, 470 pM) whole body glucose use averaged 42.5 +/- 1.6 mumol.min-1.kg-1 before and 43.6 +/- 1.9 after ACE inhibition (p = NS). Substrate concentrations and oxidative rates and energy expenditure (as estimated by indirect calorimetry) were not altered by ACE inhibition, either in the fasting state or in response to insulin. In contrast, oral glucose tolerance was significantly (p less than 0.05) improved after treatment (area under OGTT curve (AUC), 240 +/- 24 versus 282 +/- 23 mmol 2 hr.l-1). The latter change was associated with enhanced (+16%, p less than 0.05) insulin responsiveness to glucose (estimated as the insulin AUC divided by the glucose AUC) throughout the 3 months of ACE inhibition. At baseline, both the OGTT and the clamp had a marked hypokalemic effect (mean decrements in plasma potassium of 0.75 +/- 0.05 and 0.92 +/- 0.05 mmol/l, respectively) in association with plasma aldosterone reductions of 30% and 50%. Chronic ACE inhibition caused a further 20% (p less than 0.03) lowering of plasma aldosterone concentrations but attenuated insulin-induced hypokalemia. Plasma sodium, which was unaltered by the pretreatment tests, fell during the posttreatment tests (by 3 mmol/l, p less than 0.001). In the urine, the ratio of the fractional excretion of potassium to that of sodium was decreased by both oral glucose (-22%, p less than 0.01) and ACE inhibition (-21%, p less than 0.001). Higher plasma potassium levels before treatment predicted a better blood pressure response to ACE inhibition (r = 0.60, p less than 0.005).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1639460 TI - Increased insulin sensitivity in the high sodium one-kidney, one figure-8 hypertensive rat. AB - This study examines the relation between sympathetic activity and in vivo insulin mediated glucose metabolism in a rat model of acquired hypertension. Two groups of conscious, unrestrained rats were studied in the postabsorptive state: sham operated normotensive rats (n = 10) and renal-wrapped hypertensive rats (n = 10). Mean arterial pressure was increased in the hypertensive compared with the normotensive group in the fed (184 +/- 9 versus 144 +/- 6 mm Hg; p less than 0.01) and in the fasting (147 +/- 8 versus 112 +/- 7 mm Hg; p less than 0.01) state. After a 24-hour fast, hepatic glucose production, plasma glucose, insulin, and norepinephrine concentrations were similar in the two groups. Blood pressure did not change in either group during the 3-milliunits/kg.min euglycemic insulin clamp study; however, plasma norepinephrine concentration rose significantly in hypertensive (207 +/- 24 versus 329 +/- 11 pg/ml; p less than 0.05) but not in normotensive rats (229 +/- 23 versus 267 +/- 27 pg/ml; p = NS). During the insulin clamp study, the hepatic glucose production was similar in the hypertensive (3.8 +/- 0.8 mg/kg.min) compared with the normotensive (4.0 +/- 0.3 mg/kg.min) rats. Insulin-mediated glucose uptake was significantly higher in hypertensive than in normotensive rats (33.0 +/- 0.7 versus 25.8 +/- 0.8; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639461 TI - Acute hyperinsulinemia induces sodium retention and a blood pressure decline in diabetes mellitus. AB - Hyperinsulinemia supposedly contributes to hypertension in diabetes mellitus. We sought to determine if the renal and cardiovascular effects of insulin are preserved in diabetes despite resistance to its glucose-lowering effect. We studied the effects of two doses of insulin (50 and 500 milliunits/kg.hr-1), using the euglycemic clamp technique, on fractional sodium excretion, blood pressure, and heart rate in two groups of non-insulin-dependent diabetics: eight patients with and eight patients without hypertension. Hypertensive diabetics had higher basal insulin levels than normotensive diabetics (21.8 +/- 2.9 and 14.4 +/ 1.6 milliunits/l, respectively [mean +/- SEM]; p = 0.03). The degree of insulin resistance, but not plasma insulin levels, correlated with the height of mean arterial blood pressure (r = 0.60 and 0.73 at the low and high insulin dose, respectively; p less than 0.05). In contrast, the change in mean arterial blood pressure correlated negatively with the change in endogenous insulin levels during the control experiment (r = -0.41, p less than 0.02). Exogenous insulin induced a similar reduction in fractional sodium excretion in normotensive and hypertensive diabetics (43 +/- 5.9% and 48 +/- 16.4% during the low insulin dose and 57 +/- 9.1% and 62 +/- 12.5% during the high insulin dose, respectively). A decline in blood pressure was noted that correlated with the whole body glucose uptake during the high insulin dose (r = 0.52, p less than 0.05). Since heart rate response and plasma norepinephrine level during the insulin clamp were comparable in both groups, an abnormality of the baroreceptor reflex is suggested. It appears that insulin resistance, but not insulin, is primarily related to hypertension. At the same time, insulin may still exert some effect on blood pressure by way of its renal or vasodilatory, or both, action. PMID- 1639462 TI - Converting enzyme inhibition and blood pressure reactivity to psychological stressors. AB - There is considerable interest in blood pressure reactivity to psychological stressors. Because the sympathetic nervous system and the renin-angiotensin system are so responsive to stressors and are themselves the targets of many antihypertensive medications, many investigators have wondered if such medications decrease the blood pressure response to stressful stimuli. We studied 25 normotensive and 21 hypertensive men in a double-blind crossover study during which they received either placebo for 4 days or captopril (25 mg b.i.d.) for 4 days while they were hospitalized in a clinical research center. Patients were studied at resting baseline, while performing a mathematics task, and while reading out loud a disturbing newspaper article. Although captopril lowered the resting blood pressure levels, it had no effect on the amplitude of reactivity to stressors. PMID- 1639463 TI - Job strain and ambulatory work blood pressure in healthy young men and women. AB - The effect of high job strain (defined as high psychological demands plus low decision latitude at work) on blood pressure was determined in 129 healthy, nonhypertensive men (n = 65) and women (n = 64). Blood pressure measures included mean screening levels obtained in a clinical environment, mean ambulatory levels from one 8-hour workday, and the change in levels from screening to mean work levels. In male workers, men with high and low job strain showed similar blood pressures at screening, but men with high job strain showed greater increases from screening to work, resulting in higher mean work blood pressure. Occupational status was unrelated to job strain or blood pressure in men. In female workers, women with high and low job strain did not differ in any measure of blood pressure; however, there were trends for higher occupational status and greater skill discretion to be associated with higher blood pressure responses at work in women. PMID- 1639464 TI - Acute depressor effect of alcohol in patients with essential hypertension. AB - To investigate the time course of the effects of alcohol on blood pressure, we studied the response of ambulatory blood pressure, neurohumoral variables, and hemodynamics to a single moderate dose of alcohol in hypertensive patients. Sixteen Japanese men (22-70 years old) with essential hypertension who were habitual drinkers were examined under standardized conditions. On the alcohol intake day, they ingested 1 ml/kg ethanol (vodka) at dinner, and on the control day they consumed a nonalcoholic beverage. The order of the two periods was randomized. Mean ambulatory blood pressure was lower in the alcohol intake period than in the control period (125 +/- 3/74 +/- 2 versus 132 +/- 4/78 +/- 2 mm Hg, p less than 0.05), and the significant depressor effect of alcohol lasted for up to 8 hours after drinking. Blood pressure on the next day did not differ with or without alcohol intake. The acute hypotensive effect of alcohol was associated with an increase in heart rate and cardiac output and with a decrease in systemic vascular resistance as determined by echocardiography. Plasma catecholamine levels and renin activity rose significantly at 2 hours after dinner, whereas vasopressin and potassium levels fell on the alcohol day. Blood glucose and serum insulin levels were comparable between the two periods. Three patients with marked alcohol-induced flush had greater hypotensive and tachycardiac responses than those who did not show an alcohol-induced flush. The change in mean blood pressure induced by alcohol was negatively correlated with age, the baseline blood pressure, and the change in plasma norepinephrine. These results indicate that the major effect of acute alcohol intake is to lower blood pressure through systemic vasodilatation in hypertensive subjects. Ambulatory blood pressure monitoring may be useful for assessing blood pressure in habitual drinkers. PMID- 1639465 TI - Evaluation of noninvasive blood pressure monitoring devices Spacelabs 90202 and 90207 versus resting and ambulatory 24-hour intra-arterial blood pressure. AB - This study evaluated the accuracy of blood pressure values provided by the Spacelabs 90202 and 90207 devices in comparison with intra-arterial recording in 19 subjects at rest and in nine subjects in ambulatory conditions (Oxford method). At rest Spacelabs monitors reflected intra-arterial systolic blood pressure values very closely but overestimated to a considerable extent intra arterial diastolic blood pressure (Spacelabs-intra-arterial differences, -0.8 +/- 9.2, NS, and 9.1 +/- 8.8 mm Hg, p less than 0.01, for systolic and diastolic blood pressures, respectively). In ambulatory conditions Spacelabs-intra-arterial average differences in 24-hour values were +0.4 +/- 5.1 mm Hg for systolic blood pressure (NS) and +14.0 +/- 2.9 mm Hg for diastolic blood pressure (p less than 0.01) when group data were considered. The performance of both Spacelabs devices was worse when assessed in individual subjects or for each hourly interval. In spite of these differences between noninvasive and intra-arterial absolute blood pressure values, however, Spacelabs 90202 and 90207 monitors were able to faithfully reflect directional hour-to-hour changes in intra-arterial blood pressure (chi 2 = 18.2 and chi 2 = 23.1 for systolic and diastolic blood pressures, respectively, p less than 0.01). No differences were found between the performance of the two Spacelabs devices. Thus, although the absolute accuracy of blood pressure values provided by these monitors in ambulatory subjects is still limited, they seem to be suitable for studies aimed at assessing 24-hour blood pressure profiles quantitatively as well as qualitatively. PMID- 1639466 TI - Adverse effect of the calcium channel blocker nitrendipine on nephrosclerosis in rats with renovascular hypertension. AB - The effect of a 6-week treatment with the calcium channel blocker nitrendipine or the angiotensin converting enzyme inhibitor enalapril on blood pressure, albuminuria, renal hemodynamics, and morphology of the nonclipped kidney was studied in rats with two-kidney, one clip renovascular hypertension. Six weeks after clipping of one renal artery, hypertensive rats (178 +/- 4 mm Hg) were randomly assigned to three groups: untreated hypertensive controls (n = 8), enalapril-treated (n = 8), or nitrendipine-treated (n = 10). Sham-operated rats served as normotensive controls (128 +/- 3 mm Hg, n = 8). After 6 weeks of treatment, renal hemodynamics (glomerular filtration rate and renal plasma flow) were measured in the anesthetized rats. Renal tissue was obtained for determination of glomerular size and sclerosis. Enalapril but not nitrendipine reduced blood pressure significantly. After 6 weeks of therapy, glomerular filtration rate was not different among the studied groups. Renal plasma flow increased, but albumin excretion and glomerulosclerosis did not change after enalapril treatment. In contrast, in the nitrendipine-treated group albuminuria increased from 12.8 +/- 2 progressively to 163 +/- 55 compared with 19.2 +/- 9 mg/24 hr in the hypertensive controls. Furthermore, glomerulosclerosis index was significantly increased in the nitrendipine-treated group compared with the hypertensive controls (0.38 +/- 0.1 versus 0.13 +/- 0.04). In addition, glomerular size was higher in the nitrendipine-treated group (14.9 +/- 0.17 10( 3) mm2) but lower in the enalapril-treated group (11.5 +/- 0.15 10(-3) mm2) compared with the hypertensive controls (12.1 +/- 0.17 10(-3) mm2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639467 TI - Increase in erythrocyte disaggregation shear stress in hypertension. AB - The aggregation and disaggregation behaviors of red blood cells were investigated in 17 normotensive and 21 hypertensive subjects with a laser reflectometry technique, and simultaneous measurements were taken of blood viscosity with a coaxial viscometer. Increased red blood cell aggregation (26%, p less than 0.001) and disaggregation shear rate (20%, p less than 0.01) and shear stress (18%, p less than 0.01) were observed in hypertensive subjects when compared with normotensive subjects. Similar elevations in hypertensive subjects were found when the hematocrit was adjusted to 40%. Variation of red blood cell concentration caused the red blood cell disaggregation shear rate to change in an opposite direction but did not modify red blood cell aggregability and disaggregation shear stress. The increase of the reversible aggregation of red blood cells was associated with higher fibrinogen and plasma protein concentrations in hypertension. An increase in red blood cell aggregability and in the shear resistance of red blood cell aggregates may play a role in the development of the cardiovascular complication in hypertension. The quantification of red blood cell disaggregation shear stress, which represents the hydrodynamic force required to disperse the aggregates, may provide a useful parameter for clinical investigations. PMID- 1639468 TI - Hypertension, the endothelial cell, and the vascular complications of diabetes mellitus. AB - Hypertension is a major factor that contributes to the development of the vascular complications of diabetes mellitus, which primarily include atherosclerosis, nephropathy, and retinopathy. The mechanism of the pathophysiological effects of hypertension lies at the cellular level in the blood vessel wall, which intimately involves the function and interaction of the endothelial and vascular smooth muscle cells. Both hypertension and diabetes mellitus alter endothelial cell structure and function. In large and medium size vessels and in the kidney, endothelial dysfunction leads to enhanced growth and vasoconstriction of vascular smooth muscle cells and mesangial cells, respectively. These changes in the cells of smooth muscle lineage play a key role in the development of both atherosclerosis and glomerulosclerosis. In diabetic retinopathy, damage and altered growth of retinal capillary endothelial cells is the major pathophysiological insult leading to proliferative lesions of the retina. Thus, the endothelium emerges as a key target organ of damage in diabetes mellitus; this damage is enhanced in the presence of hypertension. An overall approach to the understanding and treatment of diabetes mellitus and its complications will be to elucidate the mechanisms of vascular disease and endothelial cell dysfunction that occur in the setting of hypertension and diabetes. PMID- 1639469 TI - Purification of a Trypanosoma cruzi trypomastigote 60-kilodalton surface glycoprotein that primes and activates murine lymphocytes. AB - We have purified a glycoprotein with a relative molecular mass of 60 kDa and present on the surface of Trypanosoma cruzi trypomastigotes and studied its ability to prime and stimulate the proliferation of murine spleen cells. T. cruzi trypomastigote membrane proteins were separated by preparative isoelectrofocusing. A trypomastigote 60-kDa surface protein with an isoelectric point of 4.2 was enriched by chromatofocusing and was readily purified in native form to homogeneity by gel filtration on a Superose column by use of a fast protein liquid chromatography system. Biotinylated wheat germ agglutinin, Ricinus communis agglutinin, and Datura stramonium agglutinin bound to blots containing the purified trypomastigote 60-kDa surface protein, indicating that this protein was glycosylated. The purified trypomastigote 60-kDa glycoprotein was recognized by antibodies produced during human infection, and immunoglobulin G against the purified glycoprotein immunoprecipitated a biotinylated 60-kDa molecule from the surface of trypomastigotes but not epimastigotes. Specific immunoglobulin G against the 60-kDa glycoprotein also increased the uptake of trypomastigotes and promoted parasite killing by macrophages. The purified 60-kDa glycoprotein was able to specifically activate primed lymphocytes, since there was a significant increase in [3H]thymidine incorporation by spleen cells obtained from CBA mice primed with this glycoprotein, with respect to control values. Furthermore, the 60-kDa glycoprotein did not stimulate unprimed spleen cells, indicating that the lymphoproliferation induced by this glycoprotein was specific and was not due to polyclonal activation. Our findings indicate that this T. cruzi trypomastigote 60 kDa surface glycoprotein primes and activates lymphocytes, which could lead to a beneficial immune response in the host. PMID- 1639470 TI - Evidence for B-lymphocyte mitogen activity in Borrelia burgdorferi-infected mice. AB - Borrelia burgdorferi produces a mitogen for murine B lymphocytes which can be measured in vitro by polyclonal stimulation of proliferation and immunoglobulin production (R. Schoenfeld, B. Araneo, Y. Ma, L. Yang, and J. J. Weis, Infect. Immun. 60:455-464, 1992). Sonicated B. burgdorferi cells also stimulated IL-6 production by splenocyte cultures. We have used the murine model for Lyme disease described by Barthold et al. (S. W. Barthold, D. S. Beck, G. M. Hansen, G. A. Terwilliger, and K. D. Moody, J. Infect. Dis. 162:133-138, 1990) to determine whether the B. burgdorferi B-cell mitogen is expressed during active infection. To correlate arthritic changes with immune events, we have studied two strains of mice injected with B. burgdorferi; one of them, C3H/HeJ, developed severe disease, and the other, BALB/c, developed only mild disease. C3H/HeJ mice displayed a persistent 10-fold increase in circulating immunoglobulin G (IgG) levels, a 2-fold increase in IgM levels, and a 15-fold increase in peripheral lymph node B-cell numbers, providing evidence of mitogenic activity. Infected BALB/c mice also had evidence for mitogen activity, since the IgG level in serum increased three- to fourfold. The bulk of the increase in circulating IgG levels was not directed against B. burgdorferi antigens, supporting the occurrence of polyclonal B-cell activation. Analysis of IgG isotypes pointed out a contrast between C3H/HeJ and BALB/c mice in that levels of all isotypes were elevated somewhat in both strains of infected mice but IgG2a levels were much more dramatically increased in the C3H/HeJ mice (28-fold) than in the BALB/c mice (4 fold). In this study, interleukin-6 levels were found to be persistently elevated in the serum of infected C3H/HeJ mice. Interestingly, interleukin-6 levels in serum were much lower in the infected BALB/c mice. These findings indicate that the B. burgdorferi mitogen is active in infected animals and may contribute to the inflammatory and immune response to infection. PMID- 1639471 TI - Preparation, characterization, and immunogenicity of conjugate vaccines directed against Actinobacillus pleuropneumoniae virulence determinants. AB - Conjugate vaccines were prepared in an attempt to protect pigs against swine pleuropneumonia induced by Actinobacillus pleuropneumoniae (SPAP). Two subunit conjugates were prepared by coupling the A. pleuropneumoniae 4074 serotype 1 capsular polysaccharide (CP) to the hemolysin protein (HP) and the lipopolysaccharide (LPS) to the HP. Adipic acid dihydrazide was used as a spacer to facilitate the conjugation in a carbodiimide-mediated reaction. The CP and the LPS were found to be covalently coupled to the HP in the conjugates as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and detergent gel chromatography analyses. Following a booster vaccination, pigs exhibited significantly high (P less than 0.05) immunoglobulin G antibodies against CP, LPS, and HP. The anti-CP and anti-LPS immunoglobulin G antibodies were found to function as opsonins in the phagocytosis of A. pleuropneumoniae by polymorphonuclear leukocytes, whereas antibodies to the HP neutralized the cytotoxic effect of the HP on polymorphonuclear leukocytes. No killing of A. pleuropneumoniae was observed when the effects of the antibodies were tested in the presence of complement. Thus, polysaccharide-protein A. pleuropneumoniae conjugates elicit significant antibody responses against each component of each conjugate, which could be instrumental in protecting swine against SPAP. PMID- 1639472 TI - Expression of interleukin-8 by lipopolysaccharide-stimulated bone marrow-derived mononuclear cells. AB - Interleukin-8 (IL-8) is a potent neutrophil chemoattractant, produced by a variety of immune and nonimmune cells in response to exogenous and host-derived inflammatory stimuli. We demonstrate here that a suspension of normal bone marrow mononuclear cells, consisting principally of myeloid precursors, produces IL-8 in response to stimulation with lipopolysaccharide (LPS). IL-8-specific mRNA is rapidly induced, being detected first 30 min after stimulation. IL-8 is detected by enzyme-linked immunosorbent assay within 2 h of stimulation, with steady a increase in its level through 72 h. Further studies demonstrated that LPS could serve as a primary stimulus for the expression of IL-8, since LPS challenge in the presence of cycloheximide resulted in superinduction of bone marrow mononuclear cell-derived IL-8 mRNA. These investigations suggest that the stimulatory effect of LPS is independent of other cytokines such as IL-1 beta. When compared with LPS, IL-1 beta proved to be a weak signal for the expression of IL-8 by bone marrow mononuclear cells. In a dose-response study, the maximum stimulatory concentration of IL-1 beta (300 pg/ml) resulted in the production of 500 pg of IL-8 per 10(6) cells, whereas 1 microgram of LPS resulted in the production of 5.5 ng/10(6) cells. Although IL-1 beta was not a particularly potent stimulus for IL-8 production by bone marrow mononuclear cells, peripheral blood mononuclear cells were highly susceptible to IL-1 beta challenge. In addition, the potential dependence of LPS-induced marrow-derived IL-8 production on the intermediate synthesis of IL-1 beta was further investigated. Results of studies assessing kinetics, addition of cycloheximide, and blocking with IL-1 beta neutralizing antibody were all consistent with the ability of LPS to directly induce bone marrow-derived IL-8 independently of IL-1 beta. These investigations demonstrate that bone marrow may be a significant source of IL-8 and may play a significant role in acute infectious, inflammatory responses. PMID- 1639473 TI - Functional analysis of the Ca(2+)-regulated hemolysin I operon of Actinobacillus pleuropneumoniae serotype 1. AB - The genetic determinant encoding the synthesis and secretion of hemolysin I (HlyI; gene designation, hlyI) by Actinobacillus pleuropneumoniae serotype 1 4074T was cloned in the lambda vector EMBL4. A 10.2-kb fragment that encoded hemolytic activity in the phage lysate was aligned by Southern blot hybridization to genes hlyC, hlyA, hlyB, and hlyD of the Escherichia coli hemolysin operon, and expression of the A. pleuropneumoniae genes in E. coli revealed that they have the same functions as their E. coli analogs: hlyIC encodes a protein that activates inactive 105-kDa prohemolysin I (encoded by hlyIA) to active hemolysin I, while hlyIB and hlyID are necessary for HlyIA secretion. Northern (RNA) hybridization of A. pleuropneumoniae RNA revealed that the gene cluster is transcribed as two RNA species, a major one of 3.5 kb, corresponding to hlyICA, and a second, minor one of 7.5 kb, corresponding to the whole operon, hlyICABD. The level of hlyI mRNA was substantially higher in A. pleuropneumoniae 4074T cells grown in the presence of Ca2+, supporting the view that the expression of the hlyI determinant is Ca2+ regulated. Parallel RNA hybridization with random gene probes suggested that this Ca2+ regulation is specific for the hlyI determinant. PMID- 1639474 TI - Identification of eNAP-1, an antimicrobial peptide from equine neutrophils. AB - Endogenous, cysteine-rich antimicrobial peptides known as defensins are prominent components of human, rabbit, and rat neutrophils, yet little is known about their occurrence in other mammalian species. Although we did not detect mature (i.e., processed) defensins in equine neutrophil granules, we found that these granules contained small amounts of other cysteine-rich peptides with antimicrobial activity. One of these, eNAP-1, was purified by a combination of gel permeation and reversed-phase high-performance liquid chromatography from acid extracts prepared from the cytoplasmic granules of equine neutrophils. The molecular mass of eNAP-1 was approximately 7.2 kDa, as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis. Amino acid analysis revealed that eNAP-1 had an unusually high cysteine content and that it was relatively enriched in alanine, glycine, lysine, and proline residues. The partial (N-terminal) amino acid sequence of eNAP-1 was DVQCGEGHFCHDXQTCCRASQGGXACCPYSQGVCCADQRHCCPVGF. Thirty-six of these residues (78.3%) were identical to those of a recently cloned human neutrophil peptide of unknown function and belonging to the granulin family. Homologous peptides have also been noted in rat bone marrow cells and rat kidney epithelins. We tested the ability of eNAP-1 to kill several equine uterine pathogens. Streptococcus zooepidemicus was killed most effectively, sustaining a greater than 99.8% decrease in CFU per milliliter after a 2-h exposure to 100 micrograms of eNAP-1 per ml (approximately 15 microM). Escherichia coli and Pseudomonas aeruginosa were somewhat less susceptible, manifesting 87.0 and 87.1% mean decreases in CFU per milliliter, respectively, after incubation for 2 h with 200 micrograms of eNAP-1 per ml. Klebsiella pneumoniae numbers were not significantly reduced after exposure to eNAP-1. These antimicrobial properties suggest that eNAP-1 may contribute to phagocyte-mediated host defense against equine infections. PMID- 1639475 TI - A 66-kilodalton heat shock protein of Salmonella typhimurium is responsible for binding of the bacterium to intestinal mucus. AB - Salmonella typhimurium infections have increased during the last few years. However, the interplay of virulence factors in S. typhimurium pathogenesis is still poorly understood, particularly with regard to the mechanisms and components of the bacterium which are involved in its interaction with the intestinal mucus. We have observed that S. typhimurium is aggregated by incubation with colonic mucus (guinea pig model). To quantify this phenomenon, an aggregation assay was established. By using this assay, it was found that the aggregation profile of S. typhimurium strains freshly isolated from patients (age 9 and older) with salmonellosis correlated with the severity of the disease. An isolate with high aggregation behavior was chosen for characterization of the bacterial component involved in binding to colonic mucus material. The component of S. typhimurium responsible for aggregation was purified and characterized as a 66-kDa protein which was able to completely inhibit mucus-mediated bacterial aggregation. This protein was recognized by monoclonal antibodies against the 65 kDa heat shock protein (HSP) of Mycobacterium leprae. The 66-kDa protein of S. typhimurium was inducible by incubating the bacteria at 50 degrees C and was secreted into the supernatant, from which it could be isolated in both dimeric and polymeric forms. The monoclonal anti-HSP 65, as well as a polyclonal antibody against the 66-kDa protein of S. typhimurium, caused dose-dependent inhibition of the aggregation of S. typhimurium by crude mucus preparations. This is the first report showing that a bacterial HSP is involved in mucus-mediated interaction of pathogens with the host. PMID- 1639476 TI - Presence of parasite antigen on the surface of P388D1 cells infected with Ehrlichia risticii. AB - Indirect immunofluorescence staining of macrophages infected with Ehrlichia risticii by anti-E. risticii serum revealed a punctate staining pattern on the surface of the host cell. This pattern was distinguishable by fluorescence microscopy from E. risticii bound to the surface of the macrophage and from intracellular E. risticii. The surface localization of ehrlichial antigen on infected macrophages was confirmed by electron microscopy with immunoferritin labeling. As the intracellular ehrlichial burden increased, the amount of ehrlichial antigen on the host cell surface increased. Prokaryotic protein synthesis was necessary for the maintenance of ehrlichial antigen on the host cell surface, as demonstrated by disappearance of the surface antigen following treatment with oxytetracycline. However, host cell protein synthesis was not required, as demonstrated by the continued presence of ehrlichial antigen on the surface of host cells after cycloheximide treatment. Pronase treatment abolished the ehrlichial antigen present on the cell surface, indicating that this antigen is a protein. Anti-E. risticii serum or immunoglobulin G-mediated antibody dependent cellular cytotoxicity of infected cells was demonstrated in a chromium release assay. These results imply that the parasite antigen on the host cell surface has a role in the pathogenesis of ehrlichiosis. PMID- 1639477 TI - Selection of an escape variant of Borrelia burgdorferi by use of bactericidal monoclonal antibodies to OspB. AB - Two immunoglobulin G (IgG) monoclonal antibodies (MAbs) to outer surface protein B (CB2 and CB6), affinity purified from mouse ascitic fluid, exhibited concentration-dependent inhibitory and bactericidal properties against Borrelia burgdorferi after a 24-h incubation period in spirochete medium. Fab fragments derived from these MAbs showed the same effects, indicating that they were not caused by agglutination of the organisms by the intact MAbs. The inhibition of spirochete growth in cultures containing MAbs was also detected by spectrophotometric analysis of the media. CB2 did not inhibit the growth of Borrelia hermsii or the BEP4 strain of B. burgdorferi, neither of which is recognized by the MAb. Affinity-purified IgG from hybridoma supernatants had similar effects on B. burgdorferi as the ascitic-fluid-derived IgG did, indicating that the inhibitory and bactericidal properties were not due to nonspecific toxic contaminants. The bactericidal properties of the MAbs were not complement dependent as there was none in the serum-free system. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of B. burgdorferi organisms surviving after exposure to CB2 revealed an escape variant which failed to express OspB. The continued presence of OspA in these escape variants indicates that the lack of OspB was not due to the loss of the plasmid which contains the genes for both of these proteins. PMID- 1639478 TI - hsp70 synthesis in Schwann cells in response to heat shock and infection with Mycobacterium leprae. AB - Induction of heat shock protein synthesis was monitored in murine and monkey Schwann cells exposed to elevated temperatures. Synthesis of the stress-inducible 70-kDa heat shock protein (hsp70) was detected in both murine and primate Schwann cells by metabolic labelling and by immunoblotting with a specific monoclonal antibody. hsp70 synthesis was also induced in Schwann cells after infection with Mycobacterium leprae and was detected from 24 h to 1 week postinfection. These results are discussed with respect to the possible role of heat shock proteins in immunopathological events associated with the clinical manifestations of leprosy. PMID- 1639479 TI - A 16-kilodalton lipoprotein of the outer membrane of Serpulina (Treponema) hyodysenteriae. AB - Serpulina (Treponema) hyodysenteriae P18A and VS1 were extracted by using the detergent Triton X-114 and separated into detergent and aqueous phases. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western immunoblot analysis confirmed that a membrane-associated 16-kDa antigen was hydrophobic, since it was found in the detergent phase. A 45-kDa antigen partitioned into the aqueous phase, suggesting that it was hydrophilic and may be of periplasmic origin. When spirochetes were grown in the presence of [3H]palmitic acid, a predominant 16-kDa antigen was labeled; from the results of immunoprecipitation experiments, this antigen appeared to be the same as that recognized by both polyclonal and monoclonal antisera to a previously described 16-kDa antigen. This antigen was proteinase K sensitive and was not a component of the lipopolysaccharide, which, although [3H]palmitate labeled, was resistant to proteinase K digestion. The most probable explanation is that the 16-kDa antigen is a membrane-associated, surface-exposed, immunodominant lipoprotein. PMID- 1639480 TI - Comparison of susceptibility of inbred and outbred infant mice to Escherichia coli heat-stable enterotoxin STa. AB - Comparison of the susceptibility of outbred OF1 and inbred BALB/c, C57BL/6, DBA/2, and CBA mice to heat-stable toxin (STa) of enterotoxigenic Escherichia coli was made at different levels of induced secretion. STa was able to elicit fluid accumulation into the intestine of each strain of mice; however, quantitatively different results were obtained. Results were as usual expressed by gut weight/remaining body weight ratios. Fluid accumulation weight and fluid accumulation weight/remaining body weight ratios were also estimated. Values obtained for BALB/c and OF1 mice were never significantly different, but values for OF1 mice were significantly higher than those for DBA and C57BL/6 mice at the highest concentrations of toxin (toxin dilutions of 1/2, 1/4, and 1/5). At the highest toxin concentration, gut weight/remaining body weight ratio in C57BL/6 mice was significantly lower than that for every other strain, but the fluid accumulation value obtained for DBA mice did not differ from that for C57BL/6 mice. Fluid accumulation values for DBA mice were also significantly lower at toxin dilutions of 1/5 and 1/8 than those for every other strain, and this was also the case when estimating the fluid accumulation weight/remaining body weight ratio at a dilution of 1/8. Although the intestine of each strain of mice was able to respond to STa by fluid accumulation, differences in susceptibility of the STa receptor could exist and make DBA mice more resistant to enterotoxigenic E. coli diarrhea. PMID- 1639481 TI - Kinetic analysis of the amplification phase for activation and binding of C3 to encapsulated and nonencapsulated Cryptococcus neoformans. AB - Encapsulated and nonencapsulated cryptococci exhibit quantitative and qualitative differences in their activation of the complement system. We examined the kinetics for the rapid amplification phase in which C3 was activated and bound to encapsulated cryptococci, nonencapsulated cryptococci, and zymosan particles. Yeast cells were incubated in normal human serum containing 125I-labeled C3, and bound C3 fragments were measured after 1 to 64 min of incubation. A kinetic analysis showed that the apparent first-order rate constant (k') for binding of C3 to nonencapsulated cryptococci did not differ significantly from k' for binding of C3 to zymosan particles (P greater than 0.05). However, the rate constant for binding of C3 to encapsulated cryptococci was significantly (P less than 0.001) greater than k' for binding of C3 to nonencapsulated cryptococci and zymosan particles. A plot of C3 molecules bound to encapsulated cryptococci versus time cubed was nearly linear, suggesting that accumulation of C3 in the cryptococcal capsule follows the kinetics predicted by an expanding sphere. In contrast, the plot of C3 molecules bound to nonencapsulated cryptococci or zymosan particles against time was nearly linear, but those plots against time squared or time cubed were not. This result indicates that the rate-limiting step for the addition of C3 fragments to these latter yeast cells follows the kinetics of neither the perimeter of an expanding circle nor the surface of an expanding sphere. Taken together, the results indicate that the high rate of accumulation of C3 in the cryptococcal capsule is consistent with the expected geometry of an expanding sphere of bound C3 within the three-dimensional matrix of the capsule. PMID- 1639482 TI - Mechanism of stimulation of T cells by Streptococcus pyogenes: isolation of a major mitogenic factor, cytoplasmic membrane-associated protein. AB - Our previous studies established that heat-killed Streptococcus pyogenes, as well as other gram-positive cocci, when incubated with human peripheral blood leukocytes (PBLs) in culture, induced polyclonal activation of T lymphocytes. The activated T lymphocytes included CD4+ CD8- helper T cells and CD3+ and CD4- CD8- double-negative T cells with gamma delta T-cell receptors. In the present study, we isolated a major factor with this unique mitogenic activity against human T lymphocytes from S. pyogenes. This active fraction was found in the cytoplasmic membrane (CM) of the heat-killed organisms but not in other cellular fractions such as cell walls, peptidoglycan, lipoteichoic acids, or cytoplasmic soluble fractions. An active molecule(s) was further isolated from the CM by cholic acid extraction followed by Sephacryl S-200 chromatography. The molecule was protease labile but highly resistant to heat, had a pI of greater than or equal to 9.3 and a molecular weight of 10,000 to 15,000 according to gel filtration experiments, and was termed CM-associated protein. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the protein purified by anion-exchange chromatography showed a single band with a molecular weight of 15,000, corresponding to mitogenically active regions. Purified CM-associated protein induced activation of T lymphocytes, which consisted of CD4+ CD8- T cells and CD4- CD8- double-negative T cell receptor gamma/delta + T-cell populations, as did the whole cells of S. pyogenes. PMID- 1639483 TI - Monoclonal antibodies specific for elongation factor Tu and complete nucleotide sequence of the tuf gene in Mycobacterium tuberculosis. AB - Monoclonal antibodies against mycobacterial antigens were produced by immunizing LOU/C rats with live Mycobacterium bovis BCG. The antibodies were characterized by an enzyme-linked immunosorbent assay and by sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by Western blotting (immunoblotting). One antibody, MAMB 2, reactive with a 47-kDa protein was used to screen a lambda gt11 M. tuberculosis gene library (R. A. Young, B. R. Bloom, C. M. Grosskinsky, J. Ivanji, D. Thomas, and R. W. Davis, Proc. Natl. Acad. Sci. USA 82:2583-2587, 1985). Three recombinant phages reactive with MAMB 2 in plaque lysates were isolated, and part of the insert was sequenced. The mycobacterial inserts were all expressed as proteins fused with beta-galactosidase when the phages were induced as lysogens in Escherichia coli. The entire M. tuberculosis tuf gene was obtained by screening the lambda gt11 library with a DNA probe specific for the primary clones. A phage isolated from this screening was able to express the native protein in E. coli when introduced as a lysogen. A comparison of the entire gene sequence and the deduced protein sequence with the EMBL DNA and Swiss Prot protein data libraries revealed strong homologies with elongation factors of bacteria, yeast mitochondria, and a plant chloroplast. PMID- 1639484 TI - Antibody responses to the chlamydial heat shock proteins hsp60 and hsp70 are H-2 linked. AB - The effects of both H-2 and non-H-2 genes on antibody responses to two Chlamydia trachomatis heat shock proteins (hsp60 and hsp70) were investigated. These chlamydial proteins are homologs of Escherichia coli GroEL (hsp60) and DnaK (hsp70) and are highly sequence conserved between bacterial and mammalian sources. Antibody responses among 17 different strains of mice immunized with C. trachomatis serovar B and serovar C elementary bodies were evaluated by immunoblot, radioimmunoprecipitation and enzyme-linked immunosorbent assay. Antibody responses to the two proteins displayed host genetic restriction. Of six distinctive H-2 haplotypes, only H-2d generated high antibody responses to hsp70. Five of the six H-2 haplotypes, i.e., H-2a, H-2d, H-2k, H-2q, and H-2s, produced high antibody responses to hsp60. Only the H-2b-bearing strain had low antibody responses to hsp60. By using congenic and H-2 recombinant strains, the genes responsible for regulating antibody responses to hsp70 and hsp60 were mapped to the K-IA region of the H-2 locus. In F1 hybrid crosses between high and low responders, high responses to hsp60 and hsp70 were dominant traits. Other genes outside the H-2 locus also influenced antibody responses to hsp60 and hsp70, since inbred strains of identical H-2 but different background genes displayed variable antibody responses to the proteins. The genetic control of murine immune responses to C. trachomatis hsp60, a putative chlamydial immunopathologic antigen, suggests that a similar genetic mechanism may also exist in humans, and this observation may help to explain the observed variability in the spectrum of chlamydial diseases seen in humans. PMID- 1639485 TI - Induction of inflammatory mediator release (serotonin and 12 hydroxyeicosatetraenoic acid) from human platelets by Pseudomonas aeruginosa glycolipid. AB - Purified glycolipid from Pseudomonas aeruginosa induced the generation of significant amounts of 12-hydroxyeicosatetraenoic acid (12-HETE) and serotonin release from human platelets. The release of serotonin was first observed 2 min after addition of the glycolipid and increased with time. Significant serotonin release was obtained at glycolipid concentrations above 5 micrograms/ml and increased dose-dependently up to 100% at glycolipid concentrations above 40 micrograms/ml. Glycolipid induced 12-HETE in a time- and dose-dependent manner. 12-HETE formation was first measured after 10 min of incubation and increased with time. Optimal 12-HETE formation was obtained at a glycolipid concentration of 50 micrograms/ml; higher concentrations of glycolipid led to a decrease in 12 HETE formation, indicating a cytotoxic effect. Stimulation of platelets with glycolipid (12-HETE formation and serotonin release) was accompanied by calcium influx, translocation of protein kinase C, activation of guanylylimidodiphosphate binding, and increased GTPase activity in platelet membranes within the same concentration range. PMID- 1639486 TI - Construction of a multivalent meningococcal vaccine strain based on the class 1 outer membrane protein. AB - Outer membrane complexes (OMCs) are promising vaccine candidates for protection against meningococcal disease. However, a major obstacle to this approach is the fact that the protective antibodies induced are generally type specific. In an attempt to overcome this problem, we have investigated the possibility of constructing a multivalent vaccine strain by insertion of an additional class 1 outer membrane protein-encoding gene. Starting with a derivative of strain H44/76 deficient in class 3 outer membrane protein, a second class 1 gene was inserted into the chromosome, through homologous recombination with a suicide plasmid carrying the class 1 gene from strain 2996 placed within a class 5 gene. In this way, a strain was obtained in which a class 3 protein was in effect replaced by a class 1 protein from another subtype, i.e. P1.5,2 in addition to the P1.7,16 protein of H44/76. Immunization of mice with such OMCs resulted in high bactericidal titers against both H44/76 and 2996, where normally only strain specific antibodies are induced. Mutational removal of class 3 protein from the immunizing OMCs had no detectable effect on the bactericidal titer against H44/76, whereas removal of class 1 protein led to a strong reduction. These results demonstrate the dominant role of the subtype-specific sequences of class 1 protein in the induction of bactericidal antibodies and show that construction of a multivalent OMC-based vaccine should be feasible. PMID- 1639488 TI - Modulation of tumor necrosis factor production by macrophages in Entamoeba histolytica infection. AB - The macrophage-derived mediator tumor necrosis factor alpha (TNF) is a cytokine with pleiotropic effects. TNF exhibits potent immunologic and inflammatory properties in parasitic diseases. The present study examined the production of TNF by macrophages isolated from gerbils infected with Entamoeba histolytica and by naive macrophages in response to amoebae in vitro. Amoebic liver abscess derived macrophages produced low constitutive basal levels of TNF; in response to lipopolysaccharide (LPS) stimulation, TNF production was enhanced by 14-, 11-, and 6-fold at 10, 20, and 30 days postinfection, respectively. Amoebic liver abscess-derived macrophages pretreated with either recombinant gamma interferon (IFN-gamma) or the cyclooxygenase inhibitor indomethacin augmented TNF production in response to soluble amoebic proteins and LPS. Kupffer cells and peritoneal and spleen macrophages from infected animals did not release TNF constitutively in vitro. However, TNF production in response to LPS stimulation was significantly higher at 10 and 20 days postinfection. Macrophages from infected and naive animals pretreated with recombinant IFN-gamma or indomethacin produced increased amounts of TNF in response to LPS but not in response to soluble amoebic protein stimulation. Pretreatment of naive macrophages with amoebic proteins inhibited LPS-induced TNF production by 69 to 79%; the effect of the amoebic proteins was partially reversed by indomethacin pretreatment. In contrast, IFN-gamma- and LPS activated naive macrophages produced enhanced levels of TNF in response to live amoebae and soluble amoebic proteins. Our results demonstrate that TNF production by macrophages is altered during E. histolytica infection and in response to amoebae and suggest a role for IFN-gamma and prostaglandin E2 in regulating TNF production during the infection. PMID- 1639487 TI - Induction of tumor necrosis factor (TNF) and interleukin-1 (IL-1) by Pseudomonas aeruginosa and exotoxin A-induced suppression of lymphoproliferation and TNF, lymphotoxin, gamma interferon, and IL-1 production in human leukocytes. AB - Pseudomonas aeruginosa is a dominant pathogen in infection in cystic fibrosis. This bacterium is thought to play a major role in the chronic bronchial infection induced pathophysiology. Our data showed that whole formalin-fixed heat-killed P. aeruginosa was mitogenic for human lymphocytes and induced production of substantial amounts of tumor necrosis factor alpha (TNF) in peripheral blood mononuclear leukocytes in cultures. Significant amounts of TNF were produced at 10(3) bacteria per 2 x 10(5) mononuclear leukocytes. Treatment of P. aeruginosa with polymixin B did not affect its ability to stimulate TNF production, suggesting that bacterial lipopolysaccharide is not involved. P. aeruginosa, however, did not stimulate production of the T-cell lymphokine lymphotoxin (TNF beta). Exotoxin A, considered to be an important virulence factor produced by P. aeruginosa, did not stimulate either lymphoproliferation or production of TNF. In fact, this toxin, at nontoxic concentrations, was found to depress lymphoproliferation induced by phytohemagglutinin and Staphylococcus aureus and decreased production of TNF, lymphotoxin, and gamma interferon in either lymphocytes or macrophages. This toxin similarly inhibited the production of interleukin-1 beta (IL-1 beta) and IL-1 alpha, but for the inhibition of the latter, 25-fold-less toxin was required than for inhibition of the former. Inhibition of production of TNF was as sensitive as the IL-1 alpha to exotoxin A. The effects of exotoxin A on lymphoproliferation and cytokine production could be neutralized by the addition of anti-exotoxin A antibodies. These results suggest that two mechanisms by which P. aeruginosa could contribute to the chronic bronchial infection-induced pathophysiology are the nonspecific stimulation of TNF and IL-1 and the release of exotoxin A, a toxin which depresses immune responses. PMID- 1639489 TI - Adhesion of Salmonella typhimurium to porcine intestinal epithelial surfaces: identification and characterization of two phenotypes. AB - Salmonella typhimurium 798 is known to persistently colonize swine. A key step required to initiate colonization of intestines is adhesion of the organism to the intestinal epithelium. However, S. typhimurium 798 initially failed to attach to porcine enterocytes in vitro. An enrichment procedure was used to select adhesive S. typhimurium, and when cells of one colony type were grown in tryptone phosphate broth they were adhesive. Cells from a colony with a different morphology were not adhesive. Adhesion was time dependent, with maximal adhesion occurring at 1 h. As determined by electron microscopy, cells of the adhesive phenotype had pili while none of the cells with the nonadhesive phenotype produced pili. The pili on the adhesive cells were morphologically similar to type 1 pili. Mannose (0.5%) did not affect adhesion, suggesting that the adhesin on strain 798 did not recognize mannose as a receptor. An analysis of envelope proteins from cells of both phenotypes showed that the adhesive-phenotype cells expressed at least 10 unique proteins ranging in size from 20 to 60 kDa. Absorbed antiserum against cells of the adhesive phenotype agglutinated adhesive cells and was used to detect unique surface antigens on the cells of the adhesive phenotype by Western blots (immunoblots). These antigens were in the range of 30 kDa in size. An envelope extract competitively inhibited the binding of S. typhimurium to enterocytes, as did Fab fragments prepared from the absorbed serum. Cells of both phenotypes contained two plasmids, and each had identical restriction digestion patterns. Cells of the adhesive phenotype consistently were found to be more readily phagocytosed by pig leukocytes, and once in the phagocytes they survived better than cells of the nonadhesive phenotype. PMID- 1639490 TI - Synthesis, characterization, and some immunological properties of conjugates composed of the detoxified lipopolysaccharide of Vibrio cholerae O1 serotype Inaba bound to cholera toxin. AB - Protection against cholera has been correlated with the level of serum vibriocidal antibodies. The specificity of these vibriocidal antibodies was mostly to the lipopolysaccharide (LPS). We synthesized conjugates of detoxified LPS with cholera toxin (CT) and other proteins in order to elicit serum LPS antibodies with vibriocidal activity. Treatment with hydrazine (deacylated LPS) reduced the endotoxic properties of the LPS to clinically acceptable levels and resulted in a molecule larger and more antigenic than the saccharide produced by acid hydrolysis. More immunogenic conjugates resulted from multipoint compared with single-point attachment of the deacylated LPS to the protein. The conjugates containing CT had low levels of pyrogen and no toxic activity upon Chinese hamster ovary cells and elicited booster responses of vibriocidal and CT antibodies when injected subcutaneously as saline solutions into mice; the vibriocidal titers were similar to those elicited by comparable doses of cellular vaccines. We suggest how serum vibriocidal antibodies might prevent cholera. PMID- 1639491 TI - Utilization of fractionated soluble egg antigens reveals selectively modulated granulomatous and lymphokine responses during murine schistosomiasis mansoni. AB - Worm eggs deposited in the livers and intestines of Schistosoma mansoni-infected mice secrete soluble egg antigens (SEA) and induce T cell-mediated circumoval granulomas. In the present study, we fractionated crude SEA by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and tested the fractions for granuloma elicitation and lymphokine production at different stages of the infection. SEA fraction-coupled beads were used to elicit artificial pulmonary granulomas. Acutely infected mice responded with granulomas to seven fractions (less than 21 , 25- to 30-, 32- to 38-, 60- to 66-, 70- to 90-, 93- to 125-, and greater than 200-kDa fractions) of SEA, whereas chronically infected mice responded to four fractions (60- to 66-, 70- to 90-, 93- to 125-, and greater than 200-kDa fractions). In response to both crude and fractionated SEA, granuloma T cells produced high levels of gamma interferon at the preacute (6-week) stage of infection, but production subsequently diminished. Interleukin-2 (IL-2) and IL-4 production peaked at the acute (8-week) stage of infection and concurrently decreased at the chronic (20-week) stage. At the acute stage of the infection, the granulomagenic SEA fractions also elicited IL-2 and IL-4 production; at the chronic stage, IL-2 production and, to a lesser degree, IL-4 production corresponded to SEA fractions that elicited granulomas. Isolated SEA proteins from the 32- to 38-kDa fraction demonstrated differential lymphokine responses: predominant gamma interferon and IL-2 production was elicited by the 32-kDa fraction, whereas the 35- and 38-kDa proteins elicited predominant gamma interferon and IL-4 production. However, all three proteins elicited granuloma formation. The present study reveals changes in granulomatous responses to SEA fractions during the acute and chronic stages of the infection as well as distinct phases of gamma interferon, IL-2, and IL-4 lymphokine production throughout the infection. Based on these results, it is concluded that granuloma formation and IL-2 and IL-4 production are interrelated. PMID- 1639492 TI - Effect of passive immunization with purified specific or cross-reacting immunoglobulin G antibodies against Treponema pallidum on the course of infection in guinea pigs. AB - Whole immune serum or highly purified immunoglobulin G (IgG) antibodies to Treponema pallidum exhaustively adsorbed with three strains of nonpathogenic treponemes (TPI-IgG) were used for passive immunization of inbred strain 2 guinea pigs before and after intradermal challenge with 3.4 x 10(7) virulent T. pallidum Nichols organisms. Before challenge, control animals received a similarly purified IgG fraction containing either a cocktail of antibodies against three nonpathogenic treponemes (NPTI-IgG) or IgG prepared from normal guinea pig serum (NGPS-IgG). The purified fractions contained both IgG1 and IgG2 isotypes. The antibody levels (detected by fluorescent treponemal antibody test and enzyme linked immunosorbent assay) and molecular specificities (immunoblot) of sera obtained from recipient animals before infection reflected those of the purified fractions used for immunization. Three protocols of passive immunization were used. Whole immune serum containing specific and cross-reacting antibodies afforded better protection than TPI-IgG even though asymptomatic animals were not fully protected. A single intradermal injection (0.1 ml) of TPI-IgG or NPTI-IgG into one hind leg 22 h before infection at the same site provided relatively higher protection than multiple intravenous injections (total, 15 ml) of the respective individual preparations. Since purified NGPS-IgG injected in the same animals, into the opposite hind leg, failed to protect against the challenging infection, it is reasonable to assume that specific and cross-reacting antitreponemal antibodies of the IgG1 subclass, which in guinea pigs are homocytotropic, play a relevant role in local protection. PMID- 1639493 TI - Hemolytic activity of Borrelia burgdorferi. AB - Zones of beta-hemolysis occurred around colonies of Borrelia burgdorferi grown on Barbour-Stoenner-Kelly medium containing agarose and horse blood. Blood plates were inoculated with either the infective strain Sh-2-82 or noninfective strain B 31 in an overlay and incubated in a candle jar. Both strains of B. burgdorferi displayed beta-hemolysis after 1 to 2 weeks of incubation. The hemolytic activity diffused out from the borrelial colonies, eventually resulting in lysis of the entire blood plate. Hemolysis was most pronounced with horse blood and was less intense with bovine, sheep, and rabbit blood. Hemolysis was enhanced by hot-cold incubation, which is typical of phospholipase-like activities in other bacteria. Further characterization of the borrelial hemolysin by using a spectrophotometric assay revealed its presence in the supernatant fluids of stationary-phase cultures. Detection of the borrelial hemolytic activity was dependent on activation of the hemolysin by the reducing agent cysteine. This study provides the first evidence of hemolytic activity associated with B. burgdorferi. PMID- 1639494 TI - Characterization of two genes encoding distinct transferrin-binding proteins in different Actinobacillus pleuropneumoniae isolates. AB - The gene encoding the Actinobacillus pleuropneumoniae serotype 1 transferrin binding protein (tfbA) was cloned, and the carboxy-terminal 70% of the protein was expressed as an aggregate protein in Escherichia coli. The nucleotide sequences of the tfbA genes from A. pleuropneumoniae serotypes 7 (G.-F. Gerlach, C. Anderson, A. A. Potter, S. Klashinsky, and P. J. Willson, Infect. Immun. 60:892-898, 1992) and 1 were determined, and a comparison revealed that they had 65% sequence identity. The deduced amino acid sequences showed a sequence agreement of 55%, and both proteins possessed a lipoprotein-like signal sequence. The serotype 1 TfbA protein had a predicted molecular mass of 65 kDa, compared with 60 kDa for the serotype 7 TfbA protein, and both proteins were immunologically distinct as assessed in a competitive enzyme-linked immunosorbent assay. Southern hybridization and Western blot (immunoblot) analysis of the 13 A. pleuropneumoniae type strains revealed that serotypes 2, 3, 4, 8, 9, 10, and 11 encode and express a TfbA protein highly homologous to that of A. pleuropneumoniae serotype 7 whereas the TfbA proteins and the encoding genes of serotypes 6 and 12 were highly homologous to that found in A. pleuropneumoniae serotype 1. The tfbA genes of A. pleuropneumoniae serotypes 5A and 5B were recognized, under medium-stringency hybridization conditions, by the A. pleuropneumoniae serotype 1-derived tfbA probe, and the respective proteins were weakly reactive with the antibody raised against the A. pleuropneumoniae serotype 7 TfbA protein. PMID- 1639495 TI - Site-specific growth of Nocardia asteroides in the murine brain. AB - The growth of Nocardia asteroides GUH-2 and two mutants (NG-49 and I-38-syn) in regions of the brains of BALB/c mice was determined by microdissection and viable counting. GUH-2 grew throughout the murine brain but at different growth rates that depended on the specific location. The rate of increase in total CFU per brain during GUH-2 infection was unaffected by the inoculum size; however, in five of eight brain regions, an alteration in the inoculum size resulted in altered nocardial growth rates. Mutant NG-49 showed a significantly slower rate of increase in total CFU per brain than did the parental strain, GUH-2, and significantly decreased growth rates in seven brain regions. Mutant I-38-syn showed a rate of increase in total CFU per brain similar to that of the parental strain; however, this mutant grew significantly faster in the cerebellum and pons medulla. Growth appeared to be a necessary precursor to the cellular damage that resulted in the variety of neurological disorders observed in mice infected with N. asteroides GUH-2, because mutant NG-49 exhibited a decreased ability to grow in specific regions of the brain and did not induce signs of neurological damage. In contrast, mutant I-38-syn induced neurological signs in a larger percentage of the infected animals than did parental strain GUH-2 and grew better in certain regions of the brain than did the parental strain. Furthermore, there appeared to be a relationship between the growth of N. asteroides in the substantia nigra and the induction of an L-dopa-responsive head shake that was observed in some of the mice following a sublethal intravenous injection of N. asteroides GUH-2. PMID- 1639496 TI - mxiA of Shigella flexneri 2a, which facilitates export of invasion plasmid antigens, encodes a homolog of the low-calcium-response protein, LcrD, of Yersinia pestis. AB - The plasmid-encoded invasion plasmid antigen (Ipa) export accessory locus of Shigella flexneri 2a, mxiA, was cloned, and the complete DNA sequence of the gene was determined. The mixA open reading frame was found to encode a polypeptide of 74.03 kDa with a pI of 5.02. A hydropathy analysis of the predicted protein revealed a hydrophilic C terminus and an extremely hydrophobic N terminus without a cleavable signal sequence but with several potential membrane-spanning regions. While a homology search did not reveal any significant relatedness of the mxiA DNA sequence to any known bacterial gene sequences, the derived amino acid sequence of MxiA was found to be highly homologous (68%) to the sequence of the protein encoded by the low-calcium-response locus, lcrD, of Yersinia pestis. The lcrD encodes an inner membrane regulatory protein that has an N-terminal membrane anchor and that is implicated in facilitating the export of Y. pestis outer membrane proteins (G. V. Plano, S. S. Barve, and S. C. Straley, J. Bacteriol. 173:7293-7303, 1991). Congo red binding, HeLa cell invasion, and Ipa excretion were restored in two avirulent mxiA fusion mutants when they were transformed with a cloned copy of the mxiA gene. Furthermore, the expression of the cloned mxiA gene was independent of any vector-specified promoter, suggesting that the transcription of mxiA is driven by its own promoter in this clone. In contrast, the overexpression of mxiA that resulted when it was placed under the control of the lac promoter was found to be deleterious in Escherichia coli. We conclude that mxiA is a homolog of the Y. pestis lcrD locus and may function similarly in S. flexneri, either by directly affecting the excretion of virulence factors or by regulating the expression of export accessory genes. PMID- 1639497 TI - Membrane translocation of diphtheria toxin carrying passenger protein domains. AB - For diphtheria toxin to be cytotoxic, the enzymatically active part (fragment A) must be translocated to the cytosol. We here demonstrate that additional proteins linked as N-terminal extensions can be translocated along with fragment A across the plasma membrane of toxin-sensitive cells. Thus, an extra fragment A of diphtheria toxin and some of apolipoprotein AI were translocated as passenger proteins along with mutant diphtheria toxin fragment A. Translocation was monitored by the cytotoxic effect of the additional fragment A as well as by the translocation of [35S]methionine-labelled protein to a compartment protected from externally added pronase. Cytotoxicity experiments indicated that double A fragments can also be translocated across the membrane of intracellular vesicles. The results demonstrate that the translocation apparatus used for toxin translocation is not limited to a single A fragment but can accommodate additional proteins as well. The fact that proteins as large as 20 kDa can be brought into cells by way of diphtheria toxin under both in vitro and in vivo conditions opens up the possibility of using diphtheria toxin mutants for introducing molecules with biological activity into cells. PMID- 1639498 TI - Biological activity of synthetic phosphonooxyethyl analogs of lipid A and lipid A partial structures. AB - We investigated the biological activity of four new synthetic analogs of lipid A, termed PE-1, PE-2, PE-3, and PE-4. All compounds contain an alpha-oxyethyl-linked (-O-CH2-CH2-) phosphoryl group in position 1 of the reducing glucosaminyl residue (GlcN I) of lipid A. PE-1 is a hexaacylated analog of Escherichia coli lipid A (compound 506). PE-2 differs from PE-1 in carrying two myristic acid residues at GlcN I. PE-3 has the same acylation pattern as PE-2, but GlcN I is present in the beta anomeric form. Finally, PE-4 represents an analog of tetraacyl precursor Ia (compound 406). Structure-activity relationships of these compounds were determined by measuring their capacity to induce tumor necrosis factor alpha, interleukin 1, and interleukin 6 release by human mononuclear cells and to cause mitogenicity of murine spleen cells. The results show that replacement of the glycosidic phosphoryl residue by a phosphonooxyethyl group had no substantial effect on the biological activity of compounds. However, the anomeric configuration of GlcN I was found to be of great biological relevance, as, in general, the alpha anomer (PE-2) expressed high activity, and the beta anomer (PE 3) expressed low mediator-inducing and mitogenic activity. The absence of the 3 hydroxyl groups within the acyl residues at GlcN I in PE-2 was found to only slightly affect the induction of monokines in human mononuclear cells compared with that of PE-1 or lipid A (506). These stable 1-phosphonooxyethyl analogs of lipid A may be candidates in the development of immunomodulators for the treatment of systemic endotoxicosis. PMID- 1639499 TI - Localization of the tube precipitin and complement fixation antigens of Coccidioides immitis by immunoelectron microscopy with murine monoclonal antibodies. AB - The cellular localization of the tube precipitin (TP) and complement fixation (CF) antigens of Coccidioides immitis was examined by immunoelectron microscopy with murine immunoglobulin G1 monoclonal antibodies directed against the TP and CF antigens, respectively. Immunoelectron microscopic analyses of saprobic- and parasitic-phase cells showed that the TP antigen is present at a high concentration within the inner cell wall layer and along the plasma membrane. The antigen was also detected, at a lesser concentration, within cytoplasmic vacuoles. In contrast to the predominant localization of the TP antigen in the cell walls, the CF antigen residues primarily within the cytoplasm, where it appears to be dispersed throughout the cytoplasm rather than associated with a specific cytoplasmic organelle. A sparse amount of the CF antigen within the inner cell walls was also demonstrable. The localization of the TP and CF antigens throughout the morphogenetic phases of C. immitis has important implications in antigen production and in analyses of host response in coccidioidomycosis. PMID- 1639500 TI - Immune responses to Cryptosporidium muris and Cryptosporidium parvum in adult immunocompetent or immunocompromised (nude and SCID) mice. AB - Adult murine models of Cryptosporidium infection involving Cryptosporidium muris and C. parvum were used to study immunity to cryptosporidiosis in the mammalian host. Immunocompetent BALB/c or C57BL/6 mice developed a highly patent infection with the RN 66 strain of C. muris but overcame the infection and were immune to reinfection. In contrast, severe combined immunodeficiency (SCID) mice or nude mice had a chronic infection lasting at least 109 days. The development of the C. muris infection appeared to be confined to the gastric epithelium in immunocompetent and immunocompromised mice. SCID mice injected intraperitoneally with histocompatible spleen or mesenteric lymph node cells from uninfected BALB/c mice were able to recover from the C. muris infection. The protective effect of donor spleen cells was not reduced by depletion of the B cell population but was significantly reduced by depletion of Thy.1 cells. Treatment of C57BL/6 or BALB/c mice during infection with a gamma interferon-neutralizing monoclonal antibody, but not a tumor necrosis factor-neutralizing monoclonal antibody, resulted in a significant increase in oocyst production. In the C. parvum model, a severe and eventually fatal chronic infection with a cervine isolate was established in SCID mice, with parasitization occurring in the ileum, cecum, and colon. SCID mice injected with unprimed BALB/c spleen cells prior to inoculation of C. parvum oocysts were resistant to infection. These results suggested that the two animal models should be valuable in the study of immunity to cryptosporidial infection. PMID- 1639502 TI - A novel murine model of disseminated trichosporonosis. AB - Serious infections caused by Trichosporon beigelii have been noted with increasing frequency in immuno-compromised patients. Progress in understanding the pathogenesis of this emerging infection has been limited by the lack of an animal model. We developed a CF1 mouse intravenous inoculation model of disseminated trichosporonosis to evaluate the pathogenicity of T. beigelii in transiently immunosuppressed mice. Four inocula (1 x 10(6), 1 x 10(7), 2 x 10(7), and 4 x 10(7) CFU per animal) of one clinical strain of T. beigelii 3001 were tested. Mice in groups of 10 were each injected with a single intravenous dose of one inoculum. Mortality correlated with inoculum size, as survival time was significantly shorter in mice injected with 4 x 10(7) or 2 x 10(7) CFU than in mice that received 1 x 10(7) or 1 x 10(6) CFU (P less than 0.01). Necrotizing abscesses with conidial and hyphal elements and neutrophil and macrophage infiltration were observed in all major organs examined. Resistance to infection was markedly lowered by immunosuppression with either cyclophosphamide or cortisone acetate, with a significantly shorter survival time and a greater fungal burden per organ in immunosuppressed animals than in normal animals (P less than 0.01). Nine additional strains were inoculated intravenously with around 5 x 10(6) CFU. Injection of each of these strains caused 100% mortality, in a pattern similar to that observed with strain 3001. PMID- 1639501 TI - Characterization of antibody-mediated inhibition of Pseudomonas aeruginosa adhesion to epithelial cells. AB - An enzyme-linked immunosorbent assay system was developed and used to study adhesion of Pseudomonas aeruginosa to human epithelial cells and the abilities of specific antibodies to inhibit this process. Human buccal epithelial cells coated onto microtiter plates were incubated with P. aeruginosa suspensions, and adherent bacteria were detected by using anti-P. aeruginosa serum and a horseradish peroxidase-conjugated secondary antiserum. Adhesion, quantitated as an increase in A405, varied linearly with increasing numbers of bacterial CFU added per well in the range of 10(5) to 10(8) CFU per well. Adhesion of P. aeruginosa increased following trypsinization of buccal epithelial cells. Preincubation of bacteria with monoclonal antibodies directed against P. aeruginosa outer membrane protein H2 inhibited adhesion with all eight of the isolates tested. Preincubation of P. aeruginosa with sera from infected cystic fibrosis patients also resulted in inhibition of adhesion in the enzyme-linked immunosorbent assay system. This inhibitory activity was shown to be due to two factors: P. aeruginosa-specific immunoglobulin G and a non-immunoglobulin G serum component. These data support the hypothesis that bacterial components other than pili are involved in adhesion and suggest that anti-P. aeruginosa antibodies may be of use in preventing adhesion and subsequent colonization with P. aeruginosa. PMID- 1639503 TI - Construction of stable LamB-Shiga toxin B subunit hybrids: analysis of expression in Salmonella typhimurium aroA strains and stimulation of B subunit-specific mucosal and serum antibody responses. AB - The complete Shiga toxin B subunit and two N-terminal segments of the B subunit have been inserted into a cell surface exposed loop of the LamB protein, and expression of the hybrid proteins from three different promoter systems, i.e., (i) an in vitro-inducible tac promoter that provides high-level expression, (ii) the iron-regulated aerobactin promoter presumably induced in vivo under the iron limiting conditions of the intestinal mucosal environment, and (iii) a synthetic, modified beta-lactamase promoter providing moderate level constitutive expression, has been analyzed in Escherichia coli, Salmonella typhimurium, and attenuated antigen carrier strains of S. typhimurium (aroA mutants). The hybrid vaccine strains were used to immunize mice by the oral and intraperitoneal routes. S. typhimurium aroA mutants apparently have a membrane export defect which prevents the transport of LamB and its derivatives across the cytoplasmic membrane. High-level expression of hybrid proteins through use of the tac promoter proved deleterious to the vaccine strains and prevented the production of viable cells at reasonable cell densities. The lower levels of gene expression observed with the beta-lactamase and aerobactin promoters did not have this effect. Immunization of mice with S. typhimurium aroA strains carrying the hybrid genes expressed from these two promoters resulted in significant B subunit specific mucosal and serum antibody responses. This suggests that such expression systems may be useful when incorporated into candidate antidysentery live oral vaccines for inducing protection against the effect of Shiga toxin in infections caused by Shigella dysenteriae 1 and other Shiga toxin-or Shiga-like toxin producing pathogens. PMID- 1639504 TI - Treponema denticola induces actin rearrangement and detachment of human gingival fibroblasts. AB - Spirochetes are associated with destructive periodontal diseases, and one cultivatable oral species, Treponema denticola, binds to mammalian cells and perturbs metabolism. To evaluate the cytoskeletal responses and attachment functions of human gingival fibroblasts (HGF) exposed to T. denticola, monolayers of HGF were incubated with T. denticola strains ATCC 35405, e, and e' in serum free medium. HGF retracted pseudopods, rounded up, and ultimately detached from the substratum. Scanning electron microscopy showed spirochetes in close contact with HGF surfaces; occasionally, bacteria were partially submerged between folds in the HGF membrane. Blebbing and numerous microvilli formed on the cell surface as the HGF retracted. By confocal microscopy, spirochetes were detected in contact with the HGF surface but were never found on the ventral surface of fibroblasts between the substratum and cell. Morphological alterations were associated with and preceded by actin assembly, as measured by microscopic fluorimetry: there was a 263% increase in actin fluorescence over controls within 30 min. Detachment of fibroblasts from the substratum was related to incubation time and was dependent on the concentration of T. denticola. Detachment was observed for all strains tested and was also dependent on the viability of T. denticola: UV light, heat, and metronidazole treatment markedly reduced the HGF detachment response. Detachment was also significantly reduced by the protease inhibitor phenylmethylsulfonyl fluoride. HGF viability was not significantly affected by coincubation with spirochetes, as measured by lactate dehydrogenase release. Thus, T. denticola induces rapid cytoskeletal remodelling followed by cell detachment, which might be stimulated by a bacterially associated protease but is not likely directly mediated by proteolytic degradation at the cell substratum adhesive contact points. PMID- 1639505 TI - Replicon typing of virulence plasmids of enterotoxigenic Escherichia coli isolates from cattle. AB - Plasmid DNA hybridization with probes for virulence factors used for basic replicons of plasmids was used to identify the virulence plasmids of a collection of enterotoxigenic Escherichia coli isolates from cattle. The virulence probes were derived from the genes coding for the heat-stable enterotoxin STaP and for the F5 (K99) and F41 fimbrial adhesins. The replicon probes were derived from 16 different basic replicons of plasmids (probes repFIA, repFIB, repFIC, repFIIA, repI1, repHI1, repHI2, repL/M, repN, repP, repQ, repT, repU, repW, repX, and repY). The virulence genes coding for the STaP enterotoxin and for the F5 adhesin were located on a single plasmid band in each isolate. The sizes of most of these virulence plasmids were from 65 to 95 MDa. The F41 probe failed to hybridize with any plasmid band. The virulence plasmids had multireplicon types typical of plasmids of the IncF groups. The most common basic replicon association was the triple RepFIA-RepFIB-RepFIC family association. PMID- 1639506 TI - Glucose and nonmaintained pH decrease expression of the accessory gene regulator (agr) in Staphylococcus aureus. AB - The effect of glucose on accessory gene regulator (agr) expression in Staphylococcus aureus was examined. agr is a global regulator that affects the expression of numerous genes, including those for some factors implicated in virulence, such as toxic shock syndrome toxin 1, alpha-hemolysin, and protein A. The agr locus determines two divergent transcripts, designated RNAII and RNAIII. RNAII contains four open reading frames (agrABCD), and RNAIII encodes delta hemolysin. The mechanisms responsible for agr-mediated regulation are not well understood, but it appears that the RNAIII transcript plays a central role in the regulation of a number of target genes, including those for alpha-hemolysin (hla), beta-hemolysin (hlb), protein A (spa), and staphylococcal enterotoxin B (seb+). In this study, S. aureus cultures were grown either in a shake flask system with a complex medium or in a fermentor system with a completely defined medium in which the pH and glucose concentration were maintained. Northern (RNA) blot analysis revealed that a dramatic reduction in agr expression was apparent only when the cultures contained glucose and when the pH was 5.5 or was not maintained. The effect of glucose on two agr target genes, sec+ and hla, was also studied. Glucose-containing cultures produced less sec+ and hla mRNAs at maintained pH (6.5). In addition, the glucose effect on sec+ and hla was enhanced under conditions that inhibited agr expression (i.e., pH 5.5 or a nonmaintained pH). PMID- 1639507 TI - T-cell-mediated cytotoxicity against Mycobacterium antigen-pulsed autologous macrophages in leprosy patients. AB - The involvement of CD4+ T lymphocytes in the defense mechanisms against intracellular pathogens is widely recognized. Little information is available on the generation and specificity of the cytotoxic cells that eliminate human monocytes/macrophages infected with mycobacteria. In this work, we tested whether mononuclear cells from leprosy patients could generate cytotoxic T-cell activity against autologous macrophages pulsed with Mycobacterium leprae or purified protein derivative (PPD) in a 4-h 51Cr release assay. Peripheral blood mononuclear cells from normal Mycobacterium bovis BCG-immunized controls or from leprosy patients stimulated with antigen for 7 days were used as effector cells. Paucibacillary (PB) patients and normal controls yielded more active effector cells in this system than multibacillary (MB) patients. MB patients were able to develop cytotoxicity against M. leprae, BCG, or PPD, in contrast with the immunological anergy widely described. We did not find cytotoxicity against unpulsed macrophages. Cross-reactivity was observed between PPD, BCG, and M. leprae. Only antigen-pulsed autologous macrophages were suitable as target cells. M. leprae-induced cytotoxic cells were found in both CD4+ CD8- and CD4- CD8+ T cell subsets, whereas CD4+ cells were the main component of PPD-induced cytotoxicity. In MB patients, BCG-induced cytotoxic cells were better killers of M. leprae-pulsed macrophages than cells induced by M. leprae. This is an interesting finding in view of the ongoing vaccination trials. The involvement of CD4- or CD8-mediated cytotoxicity may be important in the balance between protection and tissue or nerve damage. PMID- 1639509 TI - Antibodies to lipooligosaccharide of a Brazilian purpuric fever isolate of Haemophilus influenzae biogroup aegyptius lack bactericidal and protective activity. AB - The immunological basis for protection against Brazilian purpuric fever (BPF), a fulminant infection of young children associated with bacteremia with Haemophilus influenzae biogroup aegyptius, is unknown. Candidate antigens to which protective antibodies may be directed include cell surface proteins and lipooligosaccharide (LOS). We studied the activity of antisera to LOS purified from a BPF H. influenzae biogroup aegyptius isolate. Anti-LOS antisera contained anti-LOS antibody by enzyme immunoassay and immunoblot and no detectable anti-outer membrane protein antibodies by immunoblot. Anti-LOS antisera had minimal bactericidal activity and were not protective against the homologous strain in an infant rat model of bacteremia. Antiserum to whole bacterial cells had a titer of anti-LOS antibody similar to that of anti-LOS antisera and was bactericidal and protective. Removal of anti-LOS antibodies from anti-whole cell antiserum by affinity chromatography did not result in a loss of bactericidal activity. Serum from a normal adult contained anti-LOS antibodies and had bactericidal activity. However, anti-LOS antibodies purified from this serum did not have detectable bactericidal activity. These studies suggest that anti-LOS antibodies produced in rats are not bactericidal and do not contribute to protection against experimental bacteremia with BPF strains of H. influenzae biogroup aegyptius. PMID- 1639508 TI - Adoptively transferred anti-idiotype pulsed B cells mediate autoimmune myocarditis. AB - Syngeneic mice receiving adoptively transferred enriched B cells or splenocytes pulsed in vitro with polyclonal anti-idiotypic antibodies (anti-Ids) against anti CVB3 virus antibodies developed coxsackievirus B3 antigen-binding and virus neutralizing antibodies during a 30-day period, in addition to overt expression of autoimmune myocarditis. Adoptive transfer of anti-Id pulsed T cells resulted in delayed appearance and transient expression of antiviral antibodies, and antiviral antibodies were marginal to absent in syngeneic animals receiving anti Id pulsed macrophage populations. Proliferation analysis of recipient splenocytes indicated lack of proliferative capacity in response to monoclonal or polyclonal anti-Ids and only marginal proliferative capacity in response to coxsackievirus B3 virus antigen(s). In vitro assessment of delayed hypersensitivity in recipient animals demonstrated some specific immunity to anti-Ids in recipients receiving splenocytes or T cells. Anti-Ids expressing mimicry for heart-associated and/or viral antigen(s) interacting with B cells or other accessory cells suggest an autoantibody or anti-Id triggering of B-cell-mediated mechanisms involved in the development of myocarditis. PMID- 1639511 TI - An enhanced murine model for studies of Serpulina (Treponema) hyodysenteriae pathogenesis. AB - A defined diet was used to increase the susceptibility of mice to Serpulina hyodysenteriae. BALB/cByJ, C3H/HeN, and C3H/HeJ mice, when fed the defined diet 7 to 14 days prior to and throughout the challenge period, consistently showed higher incidences of disease than mice maintained on normal rodent chow. The use of this defined diet will increase the consistency of in vivo studies following infection with S. hyodysenteriae in the mouse model. PMID- 1639510 TI - Characterization of the humoral response induced by a peptide corresponding to variable domain IV of the major outer membrane protein of Chlamydia trachomatis serovar E. AB - A 30-amino-acid peptide corresponding to variable domain IV (VD IV) of the major outer membrane protein of Chlamydia trachomatis serovar E was conjugated to keyhole limpet hemocyanin (KLH) and used to immunize mice. The resulting antisera (anti-KLH-VD IV sera) recognized all 15 serovars of C. trachomatis when assayed by indirect immunofluorescence and Western blotting. Probing of overlapping hexameric peptides representing VD IV with mouse anti-KLH-VD IV sera revealed that two main regions of the peptide were recognized by the antisera, the N terminus of the peptide, which contains B-complex-specific epitopes, and the middle region of the peptide, which contains a species-conserved domain. When used in an in vitro neutralization assay, these antisera were able to neutralize mainly serovars in the B complex. These data provide evidence that a linear peptide corresponding to VD IV can induce in vitro protection from C. trachomatis infectivity that is subspecies specific. PMID- 1639512 TI - Cross-reactivity of polyclonal serum antibodies generated against Cryptosporidium parvum oocysts. AB - Polyclonal antibodies raised against Cryptosporidium parvum oocysts were found to cross-react with Eimeria spp. oocyst antigens in an indirect immunofluorescence assay, and sera from Eimeria spp.-infected lambs reacted with some antigens from sonicated C. parvum oocysts (between 29 to 30 and 66 to 69 kDa) by Western blot (immunoblot). No cross-reaction was observed with cystozoites of Toxoplasma and Sarcocystis spp. These results show the existence of epitopes common to C. parvum and various Eimeria spp. PMID- 1639513 TI - Mouse neutrophils lack defensins. AB - Defensins are broad-spectrum antimicrobial peptides that are abundant in human, rat, and rabbit neutrophils. We now report that neutrophils from nine strains of mice lacked appreciable defensin content. Mice may therefore be imperfect experimental surrogates for humans or rats in models of infection in which neutrophil function is significant. PMID- 1639514 TI - Elevated body temperature restricts growth of Haemophilus influenzae type b during experimental meningitis. AB - Elevation of the environmental temperature appeared to counteract the temperature depressing effects of urethane anesthetic and allowed rabbits intracisternally infected with Haemophilus influenzae type b to mimic the development of a fever following infection. Elevated core body temperature (greater than 39 degrees C) was associated with an inhibition of the growth of H. influenzae in cerebrospinal fluid (CSF) during the first 12 h postinfection, whereas bacterial growth was essentially unrestricted in rabbits with reduced (approximately 37 degrees C) body temperature. Bacterial densities 24 h postinfection were different, hyperthermic animals having log 6.0 +/- 0.4 CFU/ml of CSF and hypothermic rabbits having log 8.2 +/- 0.8 CFU/ml of CSF (P less than 0.05, Wilcoxon rank sum test). However, the growth of this bacterium in vitro, in either pooled rabbit CSF or brain heart infusion broth, was not inhibited at 39 degrees C. These results suggest that elevated body temperature associated with the development of fever during meningitis may be associated with restriction of the growth of H. influenzae in vivo but that this effect is apparently not due to an innate inability of the bacterium to grow at elevated temperatures. PMID- 1639515 TI - Infection of macrophages with Legionella pneumophila induces phosphorylation of a 76-kilodalton protein. AB - Infection of peritoneal macrophages from susceptible A/J mice with Legionella pneumophila induced phosphorylation of a 76-kDa protein. The phosphorylation occurred when macrophages were infected with a virulent strain of L. pneumophila but did not occur when they were infected with an avirulent strain or with other bacteria such as either Pseudomonas aeruginosa or Salmonella typhimurium. Also, no phosphorylation of this protein was observed when macrophages were stimulated with either lipopolysaccharide or phorbol myristate acetate. However, phosphorylation did occur in macrophages infected with a virulent strain of L. pneumophila and treated with either erythromycin to inhibit growth or with cytochalasin D to inhibit uptake of L. pneumophila by macrophages. These results support the view that phosphorylation of this protein occurs during the early phases of interaction between L. pneumophila and macrophages. The role of this specific protein in the recognition, intracellular uptake, and growth of L. pneumophila in permissive macrophages remains to be clarified. PMID- 1639516 TI - Staphylococcal toxic shock syndrome toxin 1-induced tumor necrosis factor alpha and interleukin-1 beta secretion by human peripheral blood monocytes and T lymphocytes is differentially suppressed by protein kinase inhibitors. AB - The signal transduction pathways by which staphylococcal toxic shock syndrome toxin 1 (TSST-1) induces tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) secretion were examined with various protein kinase inhibitors. TNF-alpha secretion by normal human monocytes and T cells in response to TSST-1 was suppressed by inhibitors of protein kinase C (H7) and tyrosine kinases (genistein). In contrast, the secretion of IL-1 beta was blocked by a cyclic AMP- and cyclic GMP-dependent kinase inhibitor (HA1004) as well as by H7 and genistein. These results suggest that the secretion of TNF-alpha and IL-1 beta may be differentially regulated by TSST-1 and that protein kinases play an important role in mediating cytokine responses to the toxin. PMID- 1639517 TI - Acanthamoebae bind to glycolipids of rabbit corneal epithelium. AB - By use of a thin-layer chromatogram (TLC) overlay procedure, 35S-labeled acanthamoebae were shown to bind to seven glycolipids of rabbit corneal epithelium. Corneal epithelial cells were grown in culture and were subjected to Folch extraction to isolate a chloroform-rich lower phase containing neutral glycosphingolipids (NGSL) and an aqueous upper phase containing gangliosides, i.e., sialic acid-containing glycolipids. Thin-layer chromatography of the upper phase revealed the presence of 10 ganglioside components. Acanthamoebae were shown to bind to four of these components, referred to as 2, 3, 6, and 7. On TLC plates, ganglioside components 2 and 3 migrated slightly ahead of the glycolipid standard GD1a, component 7 comigrated with standard GM3, and component 6 migrated a little more slowly than GM3. Likewise, of the 10 NGSL known to be present in the lower phase, acanthamoebae bound to components 1, 5, and 6. NGSL components 1, 5, and 6 migrated on TLC plates with relative mobilities similar to those of standards asialo GM1, asialo GM2, and ceramidetrihexoside, respectively. We propose that one or more of the Acanthamoeba-reactive glycolipids of corneal epithelium identified in this study may play a role in the pathogenesis of Acanthamoeba keratitis by mediating the adherence of the parasites to the cornea. PMID- 1639519 TI - Purification and immunological studies of the cross-reaction between the 65 kilodalton gonococcal parietal lectin and an antigen common to a wide range of bacteria. AB - The 65-kDa gonococcal parietal lectin (GPL) has been purified and found to have a lectinlike activity exhibiting both structural and immunological similarities to the common antigen family. Ultrastructural localization of GPL was done by using anti-GPL monoclonal antibodies: GPL is a major component of the outer membrane and is also present in blebs formed by gonococci. PMID- 1639518 TI - Frequent loss of Shiga-like toxin genes in clinical isolates of Escherichia coli upon subcultivation. AB - Forty-five consecutive patients with various gastrointestinal disorders were identified as having Shiga-like toxin (SLT)-producing Escherichia coli infections. This was shown by the cytotoxic effect of stool extracts in Vero cell cultures which was neutralizable by antibodies to SLTs and by isolation of E. coli that hybridized with DNA probes complementary to SLT-I and SLT-II sequences. When we tested the same strains for SLT genes after subcultivation, the isolates from 15 patients became negative by colony hybridization and polymerase chain reaction and failed to produce SLTs. The instability of SLT genes warrants direct screening methods for clinical material and the development of new culture methods to prevent the loss of SLT genes. PMID- 1639520 TI - Serotype diversity and antigen variation among invasive isolates of Ureaplasma urealyticum from neonates. AB - Ureaplasma urealyticum has previously been isolated from the cultured cerebrospinal fluid of 13 of 418 newborn infants; additional bloodstream isolates were obtained from the same population. Ten of the 13 cerebrospinal fluid and 3 bloodstream isolates were available for serotyping in the present study. By the use of serotype-specific reagents, including monoclonal antibodies, 70% of the cerebrospinal fluid isolates were identifiable as serotype 1, 3, 6, 8, or 10; i.e., they represented 5 of the 14 established serotypes or both presently defined genomic clusters. One of the bloodstream isolates was identified as serotype 3. Our data support the hypothesis that the property of invasiveness for unreaplasmas is likely not limited to one or a few particular serotypes among the 14 established serovars. Additionally, our study has shown that even in isolates of the same serotype, there can be size variation in the antigens expressed. Therefore, it would appear that many serotypes are invasive and that perhaps antigen variability and host factors may be more important determinants for ureaplasma infections than different serotypes per se. PMID- 1639522 TI - Blood flow outside regularly spaced hollow fibers: the future concept of membrane devices? PMID- 1639521 TI - Is atherogenesis accelerated in hemodialysis patients. PMID- 1639523 TI - Characterisation and evaluation of a new double lumen central venous catheter. AB - The performance of a new double lumen central venous haemodialysis catheter was tested in two laboratory models. In a bench model the patient's venous system was simulated by a reservoir from which water or glycerol was drawn through a fixed tube. A double lumen silastic catheter was then inserted into the tube, as it would in a major vein, with the tip directed away from the direction of flow. The catheter was linked to a dialysis circuit incorporating pressure sensors and dye was infused at constant rate so that recirculation at the tip could be measured and found to be less than 5%. The same catheters were inserted operatively into the superior vena cava via the external jugular vein of three pigs (weight 27-31 kg). The catheters remained patent for four weeks and when connected to an extracorporeal circuit had recirculation and pressure flow characteristics comparable to the bench model in the range 50-400 ml/min. The new double lumen catheter is worthy of clinical evaluation. PMID- 1639524 TI - A new central supply system as alternative source for bicarbonate dialysate. AB - Bicarbonate dialysis is mandatory for high efficiency treatment. In most cases bicarbonate is delivered either as prepacked powder or as a stable liquid concentrate in 6-10 I plastic containers. With a newly designed central supply system (CSS) using 800 I tanks of custom-made sterile and pyrogen free concentrates, we investigated the risk of bacterial contamination of dialysate in a 30-bed dialysis unit. During three months, samples of reverse osmosis (RO) water, concentrates and dialysate were taken every two weeks. Colony forming units (CFU) were counted after 48 h incubation. Further samples were taken during nine months of continuous use of the CSS without further intermittent disinfection. None of the samples had greater than 10/ml CFU. Pseudomonas, corynebacteria and enterobacter were the predominant species. In summary, this CSS proved reliable in providing bacteriologically safe bicarbonate dialysate as defined by international standards (CFU less than 200/ml). It significantly reduces costs, workload and environmental pollution by plastic waste. PMID- 1639525 TI - Correlation of blood pressure in end-stage renal disease with platelet cytosolic free calcium concentration during treatment of renal anemia with recombinant human erythropoietin. AB - The hemodynamic hallmark of hypertension complicating the treatment of renal anemia with recombinant human erythropoietin (rHu-EPO) is increased total peripheral vascular resistance, but the mechanisms underlying the arteriolar vasoconstriction are still an enigma. We studied body fluid volumes, plasma renin activity, plasma norepinephrine, and calcium metabolism in platelets in 40 previously normotensive hemodialysis patients before and after 12 weeks of rHu EPO treatment. Partial correction of anemia caused a rise in arterial pressure (94 +/- 6 mmHg vs 124 +/- 7 mmHg, p less than 0.05) and in platelet cytosolic calcium concentration (113 +/- 5 nM vs 171 +/- 18 nM, p less than 0.05) in eight patients. Hypertensive patients had significantly higher plasma noradrenaline concentrations, but they did not differ significantly in body fluid volumes and plasma renin activities. There was a close correlation between free calcium concentration in platelets and mean arterial pressure in patients developing rHu EPO-induced-hypertension (r = 0.95). Short-term antihypertensive treatment resulted in a reduction of free calcium concentrations in platelets and a concomitant fall in blood pressure. The main results of the present studies suggest that rHu-EPO-induced hypertension might be associated with altered cellular calcium homeostasis and hyperactivity of the sympathetic nervous system. If rHu-EPO therapy induces alterations of pressor factors or the hormone itself raises the cytosolic calcium not only in platelets but also in vascular smooth muscle cells, altered cellular calcium influx may contribute to the arteriolar vasoconstriction. PMID- 1639526 TI - Hemodynamic and cardiac effects of erythropoietin in patients on regular dialysis. AB - The long-term impact of erythropoietin (EPO) treatment on cardiac structures and function was prospectively studied in eight hypertensive (Group I) and seven normotensive (Group II) patients on hemodialysis (HD). Doppler-echocardiograms were done before EPO and at two and twelve months of treatment. Mean hemoglobin (+/- SD) before EPO was 6.4 +/- 0.9; it rose significantly up to two months and then remained constant. At two months, cardiac index (CI) had significantly decreased, while peripheral vascular resistances increased. Five patients required increased antihypertensive drug treatment. No changes were seen in myocardial parameters at this short follow-up. After one year, left ventricular mass index (LVMi) decreased (p less than 0.05) in both groups concomitantly with a decrease in diastolic diameter and septum and posterior wall thicknesses. Basal LVMi was higher in Group I than in Group II, and after one year the regression was more marked in Group II. Left cardiac work showed prompt and steady improvement in both groups. Maintained partial correction of anemia with EPO during one year was associated with a return to normal of high CI, decreased left cardiac work and impressive regression of left ventricular hypertrophy. PMID- 1639527 TI - An equation for calculating postdialysis plasma sodium. AB - Well defined dry weight is a must for adequate UF control during haemodialysis (HD). However, interdialytic weight gain (delta BW) must not be excessive. delta BW is closely related to interdialytic thirst which in turn is strongly influenced by post-dialysis plasma sodium (CPNa post), but little is known about the desired CPNa post. The points below serve as a basis for establishing this value. a) Thirst is mediated by osmoreceptors. b) A strong correlation has been found between delta BW and intradialytic increase in plasma sodium but no such correlation exists with the interdialytic increase in plasma urea. This indicates that fluid intake between dialyses depends solely on electrolytes. c) Pre dialysis plasma sodium in an individual is stable, indicating that the patient is at his "set value" of electrolyte osmolality. d) Half of the potassium removed during HD comes from the extra- and half from the intracellular space. Assuming that it is desirable not to disturb a patient's pre-dialysis osmotic steady state, it can be calculated that the desired CPNa post should be higher than the pre-dialysis value by half of the intradialytic plasma potassium drop, i.e., approx. CPNa post = CPNa pre + 1 to 2 mmol/l. PMID- 1639528 TI - Dynamic catheterography in the early diagnosis of peritoneal catheter malfunction. AB - The dynamic catheterography is an image technique that allows to study the peritoneal solution inflow and outflow phases in case of catheter malfunction. The examination is carried out in three subsequent steps: 1) direct examination without contrast media in order to define the position of the catheter inside the abdomen; 2) low speed catheterography by normal injection of 10 ml of hydrosoluble contrast medium to verify the patency of the cannula; 3) high speed catheterography by 30 ml hydrosoluble dye injected with an automateds high pressure system to study the inflow phase, the fluid distribution in the peritoneal cavity and the patency of the catheter holes. Different radiographic patterns can be found: dislocation of the catheter tip, KinKing, one way obstruction, inner lumen obstruction. The procedure is simple, safe and reliable for a correct diagnosis and for the choice of a successful therapeutic approach to peritoneal catheter malfunction. PMID- 1639529 TI - Blood coagulation, fibrinolytic and inhibitory profiles in renal transplant recipients: comparison of cyclosporine and azathioprine. AB - Renal transplant recipients treated with cyclosporine (CS) have been reported to be at increased risk of thrombotic complications. The present study was intended to examine the blood coagulation, fibrinolytic, and inhibitory systems in such patients. Eight transplant recipients on maintenance immunosuppression with CS and prednisone were studied. Five transplant recipients maintained on azathioprine (AZA) and prednisone and 32 normal volunteers served as controls. Plasma antigen concentrations and/or activities of various proteins in the above pathways were measured. Both the CS and AZA groups exhibited significant elevations of factor IX activity, von Willebrand factor (vWF), D-dimer, protein C and tissue type plasminogen activator (t-PA) levels when compared with the normal controls. In addition, CS group showed a significant elevation of alpha 2 macroglobulin activity and AZA group showed a significant reduction in factor XII activity when compared with the normal controls. Comparison of data from CS and AZA groups revealed higher factor XII activity and vWF concentration in the former group. In conclusion, transplant recipients treated with long-term cyclosporine and prednisone exhibited significant elevation of plasma vWF, D dimer and protein C concentrations. In addition, both CS and AZA-treated transplant recipients showed increased plasma concentrations of D-dimer and t-PA. The latter observations suggest in vivo thrombin generation, fibrin formation and degradation. PMID- 1639530 TI - Formation of thrombin-antithrombin III complex using polyamide and hemophan dialyzers. AB - The recently developed ELISA for the thrombin-antithrombin III complex (TAT) is a sensitive, specific, and simplified means of detecting intravascular coagulation. For further evaluation of the thrombogenicity of a polyamide (P) and a Hemophan (H) hollow-fibre dialyzer a cross-over study was done in ten stable patients on maintenance hemodialysis. At the same doses of heparin (mean bolus of 30 U/kg bw and maintenance doses of 86 U/kg bw), thrombin time and partial thromboplastin time were significantly lower using H. At the end of dialysis TAT was significantly higher in H (mean +/- SEM before HD 3.57 +/- .56, at 240 min 14.9 +/- 6.5 ng/ml, p less than 0.05, Wilcoxon-test) than in P (before HD 4.36 +/- .98, at 240 min 8.95 +/- 3.0 ng/ml, p less than 0.05 H 240 vs. P 240, Wilcoxon test). Visible clotting was more pronounced in the H filter. Among other favourable features of blood compatibility the polyamide/polyvinylpyrrolidone copolymer with a hydrophilic/hydrophobic microdomain structure has less thrombogenicity. The modified cellulosic membrane H has advantages in complement activation and leukocyte depression, but thrombogenicity seems less favourable since the incorporated diethyl-amino-ethyl groups with their positive charge bind and inactivate negatively charged heparin. PMID- 1639531 TI - A cardiac assist device as blood supply in ischemic heart disease. AB - Before the event of modern bypass surgery revascularisation of the heart was tried with the transplantation of pedicled muscle flaps onto the heart. For patients who cannot undergo bypass surgery this method could be--in a modified way--of help. This was shown in 12 dogs. In those a free muscle flap was transplanted onto the heart which had undergone a previous artificial infarction. The muscle flap was anastomosed with the a. mammaria, venous flow was directed into the right atrium. After 5 months the muscle was almost completely atrophic, but a fit capillary network was penetrating the underlying myocardium. PMID- 1639532 TI - Transcutaneous transmission of digital data and energy in a cochlear prosthesis system. AB - This paper describes the inductive power and data link employed in the CAP Cochlear Prosthesis System (CAP stands for Combined Analog and Pulsative Stimulation Strategy). The inductive link consisting of a parallel-tuned receiver resonant circuit weakly coupled to a series-tuned transmitter resonant circuit, is driven by a self-oscillating class-E-tuned power amplifier. The class-E concept allows coupling-insensitive high-efficiency transcutaneous transmission of power. In the CAP implant, variations of the coil distance within a range of 0 to 9 mm result in changes of the implant supply voltage which are lower than 10%. Within this coil distance range, the mean overall efficiency is 49%. In view of the excellent switching properties of the class-E tuned power oscillator, a practical scheme for data transmission is ASK (Amplitude Shift Keying). To ensure constant energy flow and easy synchronization of the bitstream in the implant, a self-clocking bit format is employed. PMID- 1639533 TI - Comparison of plasma separation and immunospecific LDL-elimination in severe hypercholesterolemia. PMID- 1639534 TI - Colon cancer in Argentina. I: Risk from intake of dietary items. AB - A case-control study has been conducted to investigate the relationship between dietary components and risk of colon cancer in the La Plata area of Argentina. Cases are 110 patients newly diagnosed with colon cancer in 10 major hospitals between 1985 and 1986. Two neighbourhood controls per case were individually matched by age, sex and place of residence. Personal interviews elicited information on frequency of consumption of 140 food items during the 5-year period up to 6 months prior to interview. Risk is analyzed by quartiles of individual food items and groups of items. Multivariate conditional logistic regression modelling indicates that consumption of eggs is associated with increased risk for colon cancer (odds ratios by quartile: 1.0, 1.58, 2.02, 4.66), as are some dairy products (ORs of 1.93 for the highest quartile of consumption of cheese). Intake of vegetables, fish and poultry is associated with statistically significant decreasing risk (ORs of 0.075, 0.39 and 0.39, for the highest categories of consumption of vegetables, fish and poultry, respectively). The risk for red meat does not consistently increase as consumption increases. Risks are not altered by the inclusion of potential confounders such as education or body mass index. These findings confirm those of several previous studies and are of particular interest, since the Argentinean diet typically includes a high intake of red meat. PMID- 1639535 TI - An analysis of autologous T-cell anti-tumour responses in colon-carcinoma patients following active specific immunization (ASI). AB - As part of a phase-II clinical trial of post-operative active specific immunization (ASI) with virus-modified autologous tumour cells (AuTu) in colorectal carcinoma patients, we have analyzed in vitro anti-AuTu immune responses with lymphocytes isolated from the peripheral blood (PBL) of 5 treated patients. The PBL of 3 "responder patients", those who developed a positive DTH reaction to AuTu, when stimulated in standard in vitro autologous lymphocyte tumour-cell cultures (ALTC), showed cytotoxic anti-AuTu reactivity only in association with natural-killer-cell(NK)-like activity. We removed nonspecific cytotoxic cells (CD56-positive) from PBL of colon carcinoma or melanoma patients and positively selected T cells with strong CD8 staining (CD8hi) using FACS. Following in vitro stimulation, specific cytotoxic T cells (CTL) directed against either autologous EBV-transformed B cells (AuEBV-B) or autologous melanoma cells were identified in the CD8hi T-cell population. However, even using this novel technique, no specific CTL against autologous colon carcinoma cell lines were detected in PBL from ASI-treated patients (2 DTH responders and 2 DTH non responders). If AuTu-specific CTL precursors existed in these blood samples, their frequency must have been very low (less than 1 in 8 x 10(4) CD8 positive T cells). Sorted CD4 T cells from these patients, in the presence of autologous antigen-presenting cells, showed no specific anti-tumour proliferative response, and in one instance we observed inhibition of proliferation in the presence of tumour cells. PMID- 1639536 TI - A prospective study of transmission by transfusion of HTLV-I and risk factors associated with seroconversion. AB - To evaluate the risk of transfusion-related transmission of HTLV-I in Jamaica, a prospective study was initiated, prior to availability of a licensed HTLV-I serological screening assay. This information would prove useful in formulating strategies for blood-donor screening. We followed 118 pre-transfusion HTLV-I negative transfusion recipients at monthly intervals post-transfusion for 1 year. Laboratory and questionnaire data were obtained at each visit to evaluate the clinical and immunological status of recipients. Cumulative incidence of HTLV-I seroconversion was estimated and risk-factor data associated with seroconversion among 66 HTLV-I-exposed transfusion recipients were analyzed. Seroconversion occurred in 24/54 (44%) of recipients of HTLV-I-positive cellular blood components, 0/12 recipients of positive non-cellular donor units and 0/52 recipients of HTLV-I-negative donor units. Significant risk factors associated with recipient seroconversion were receipt of a seropositive cellular blood component stored for less than one week [odds ratio (OR) = 6.34, 95% confidence interval (CI) = 1.83 to 21.92], male sex (OR = 4.79, 95% CI = 1.15 to 20.0) or use of immuno-suppressive therapy at time of transfusion (OR = 12.20, 95% CI = 0.95 to 156). Risk of blood-borne infection per person per year in Jamaica was estimated to be 0.009%. Our results confirm that blood transfusion carries a significant risk of HTLV-I transmission and that screening of donor blood effectively prevents HTLV-I seroconversion. Recipients at greatest risk for seroconversion were those who required multiple transfusions or who were receiving immunosuppressive therapy at the time of transfusion. These patients should be given priority in receiving selectively screened blood components, if universal blood-donor screening for HTLV-I is not possible. PMID- 1639537 TI - Alcoholism and liver cirrhosis in the etiology of primary liver cancer. AB - The aim of this study was to determine the risk of developing primary liver cancer in patients with a diagnosis of alcoholism, liver cirrhosis, or both. Three population-based, mutually exclusive cohorts were defined on the basis of hospital discharge diagnosis between 1965 and 1983. Complete follow-up through 1984--excluding the first year of follow-up--showed that among 8,517 patients with a diagnosis of alcoholism, 13 cancers occurred, vs. 4.2 expected (standardized incidence ratio (SIR) = 3.1; 95% confidence interval (CI) = 1.6 to 5.3); among 3,589 patients with liver cirrhosis, 59 cancers occurred, vs. 1.7 expected (SIR = 35.1; 95% CI = 26.7 to 45.3), and among 836 patients with both diagnoses, 11 cancers occurred, vs. 0.3 expected (SIR = 34.3; 95% CI = 17.1 to 61.3). Thus, alcoholism alone entailed a moderately increased risk and alcoholism with liver cirrhosis did not increase the high relative risk for liver cancer more than cirrhosis alone. We conclude that alcohol intake may be a liver carcinogen only by being causally involved in the development of cirrhosis; and further, that the risk of developing liver cancer following cirrhosis in this population is similar to or higher than that after chronic hepatitis-B-virus infection in other Western countries. PMID- 1639538 TI - In vitro activity of novel antifolates against human squamous carcinoma cell lines of the head and neck with inherent resistance to methotrexate. AB - A series of 7 human squamous carcinoma cell lines of the head and neck (HNSCC), grown in standard medium containing high folate concentrations and in "folate conditioned" medium containing nanomolar concentrations of folates, were all found to be sensitive (IC50: less than or equal to 50 nM) in growth-inhibition studies to methotrexate (MTX) following drug exposure for 7 days. However, when MTX exposure was limited to 24 hr, only 2 out of 7 HNSCC cell lines were sensitive to MTX (IC50: less than 500 nM), 2 were moderately sensitive (IC50: 1-2 microM), and 3 exhibited inherent resistance to MTX (IC50: greater than 250 microM). In these last 3 cell lines, the mechanism of resistance was not correlated with altered membrane transport of MTX or changes in dihydrofolate reductase activity, but rather was associated with a 3-fold lower activity of intracellular folylpolyglutamate synthase (FPGS) activity compared to MTX sensitive HNSCC cells. The 3 cell lines exhibiting inherent resistance to a short exposure to MTX, however, did not show inherent cross-resistance after exposure for 24 hr to one or more of 3 novel antifolate compounds. These compounds, which appear to be more efficiently transported and polyglutamylated than MTX, include: 10-ethyl-10-deazaaminopterin (10-EdAM), 2-desamino-2-methyl-N10-propargyl-5,8 dideazafolic acid (ICI-198,583), and 5,10-dideazatetrahydrofolic acid (DDATHF). These results indicate that antifolate membrane transport and intracellular FPGS activity are important factors in determining sensitivity or resistance of HNSCC cells to short-term antifolate compound exposures. PMID- 1639539 TI - Inhibitory effects of human interferons on the immortalization of human, but not rabbit, T lymphocytes by human T-lymphotropic virus type-I (HTLV-I). AB - The effects of human interferon (IFN)-alpha, -beta, and -gamma on the immortalization of human and rabbit lymphocytes by human T-lymphotropic virus type-I (HTLV-I) have been investigated. The immortalization of human peripheral blood lymphocytes co-cultured with lethally X-ray-irradiated HTLV-I-producer cells, MT-2, was blocked in the presence of more than 40 u/ml human recombinant IFN-alpha or more than 200 u/ml human natural type IFN-beta. However, rhIFN-gamma did not block immortalization by HTLV-I even at higher doses. On the other hand, the presence of high doses of hIFN-alpha, -beta, or -gamma did not exhibit any biological effect on the immortalization of rabbit peripheral-blood lymphocytes co-cultured with lethally X-ray-irradiated MT-2 cells. Integration of the full length of HTLV-I genome was detected in every transformant by Southern blot analysis. All cell lines established were CD4+/CD8 divided by T-lymphocytes, except for one cell line of CD4+/CD8+. Morphologically intact HTLV-I production was observed by electron microscopy in these cells. Our results indicate that HTLV-I released under the strongly suppressed condition in the presence of IFNs remains active and able to immortalize T lymphocytes. It is also suggested that immortalization of human T lymphocytes by HTLV-I can be inhibited by the antiviral state induced by the treatment with low doses of hIFN-alpha and -beta, whereas immortalization of rabbit T lymphocytes is not inhibited because of the species specificity of hIFNs. PMID- 1639540 TI - The effect of schedule, protein binding and growth factors on the activity of suramin. AB - Suramin has been shown to have antiproliferative activity, either by blocking the binding of growth factors to their receptors or by inhibiting critical cellular enzymes. In 6 different cell lines from 5 tumour types (MCF-7, MCF-7/ADRR, PC3, HT-29, UM-SCC-11B and SW-1573/IR500), we studied the effect of scheduling of suramin, of FCS and of human serum albumin (HSA), of epidermal growth factor (EGF) and of the addition of growth factors in serum-free medium on the activity of suramin. The concentration of suramin which gave 50% growth inhibition (IC50) varied from 45 microM in SW-1573/IR500 to 153 microM in PC3 cells grown in medium supplemented with 5% FCS, after 6 days of continuous exposure. Exposure for more than 4 days did not enhance the sensitivity to suramin, except in PC3. At exposure to suramin for 1 day followed by 5 days recovery, high IC50 values (greater than 0.5 mM) were observed in MCF-7 cells. In medium with 1% and 0.5% FCS these values were 3 to 8 and 14 to 26 times lower respectively. Addition of HSA increased the IC50 in PC3 and MCF-7 cells. Suramin binding to protein was dependent on the concentration of protein and of suramin. Excess of EGF in medium with different FCS concentrations did not change the IC50 values of suramin in PC3 and MCF-7 cells. Addition of EGF, fibroblast growth factor or platelet derived growth factor in PC3 cells cultured in serum-free medium did not increase the IC50 values. Suramin was active against these 6 cell lines at clinically achievable concentrations. This activity varied depending on the cell line, exposure time and suramin concentration. The most significant factor interfering with sensitivity to suramin was the amount of protein present in the culture medium. PMID- 1639541 TI - Correlation of myc expression with the growth-arrested and transformed phenotypes in hybrids between a T lymphoma and an antigen-responsive T-cell line. AB - Fusion of the YACUT lymphoma cell line with the Mls-1a-antigen-specific non tumorigenic T-cell line G4 produced growth-arrested hybrids that could be induced to proliferate in the presence of Mls-1a antigen. Prolonged growth of such hybrids by repeated antigenic stimulation resulted in the appearance of autonomously growing hybrid lines. Of the 4 antigen-independent hybrid clones, I was weakly tumorigenic (25% incidence) while the other 3 were highly tumorigenic (100% incidence). In the growth-arrested hybrids the de-regulated c-myc expression characteristic of the YACUT cells was suppressed. In the autonomously growing clones, however, c-myc expression had reverted to the levels of the lymphoma parent and 1 to 2 extra copies of chromosome 15 were consistently present. These results indicate that repeated antigenic stimulation somehow abrogated the down-regulation of c-myc in the growth-arrested hybrid lines. The increase in the number of copies of chromosome 15, however, suggests that genes located on this chromosome may abolish the effect of the negative regulatory functions of the non-malignant parent in a gene-dosage-dependent manner. PMID- 1639542 TI - Therapy of primary and metastatic mouse mammary carcinomas with doxorubicin encapsulated in long circulating liposomes. AB - The purpose of our study was to compare the therapeutic effects of doxorubicin in 3 different formulations: (1) in PBS, (2) in conventional liposomes composed of egg phosphatidylglycerol/egg phosphatidylcholine/cholesterol/dl-alpha tocopherol, and (3) in sterically stabilized, long-circulating "Stealth" liposomes composed of hydrogenated soy phosphatidylcholine/cholesterol/polyethylene glycol distearoylphosphatidylethanolamine. The doxorubicin formulations were used to treat recently implanted and well-established, growing primary mouse mammary carcinomas, and to inhibit the development of spontaneous metastases from intra mammary tumor implants. In the treatment of recently implanted primary tumors, the formulations were given in 3 i.v. injections over 15 days, starting 3 or 10 days after tumor implantation. In the treatment of well-established primary tumors, the mice received 4 i.v. injections over 22 days, starting an average 38 days after tumor implantation. In the preventive treatment against metastases, the formulations were given in 4 i.v. injections over 22 days, starting 22 days or 58 days after primary tumor implantation. The Stealth liposome formulation was significantly more effective than the conventional liposome formulation or the free drug in reducing the incidence of metastases from intra-mammary implants of tumor MC19 and tumor MC65, in curing mice with recent implants of tumor MC2A, tumor MC2B, and tumor MC65, and in increasing the 8-week survival of mice with well-established implants of tumor MC2B. It is concluded that the long circulation time of the Stealth liposome doxorubicin formulation accounts for its superior therapeutic effectiveness. PMID- 1639543 TI - Growth in serum-free medium of NIH3T3 cells transformed by the EJ-H-ras oncogene: evidence for multiple autocrine growth factors. AB - Rodent fibroblastic cells transformed by ras oncogenes can grow in serum-free (S ) medium. We have studied clonal lines of mouse NIH3T3 fibroblasts transfected with the EJ-H-ras oncogene, and observed that practically all become independent of exogenous growth and attachment factors shortly after transfection. Moreover, all the clones tested soon form anchorage-independent (AI) colonies in S- medium, and most give rise to spheroids able to grow in suspension. The cell-conditioned S- medium of the transformed (TR) cells stimulates autocrinally the AI and anchored growth of these cells, in the absence of serum, and it contains growth factors related to TGF-alpha (or EGF), PDGF and bFGF, and other uncharacterized factors. Some of these factors are not found, or are found only in very small amounts, in the S- medium of non-transformed NIH3T3 cells, which also stimulates the growth of the TR cells, in the absence of serum. In addition, the TR cells contain 4-6 times more cell-associated bFGF than the non-transformed cells and release more latent TGF-beta activatable by acid treatments. However, no active TGF-beta is secreted by either cell type. Activated TGF-beta and pure TGF-beta 1 stimulate the growth of the anchored TR and NIH3T3 cells, but inhibit the AI growth of the TR cells. Another inhibitor of this growth is also found in the concentrated medium of the NIH3T3 cells. PMID- 1639544 TI - Human RT-4 bladder carcinoma is highly metastatic in nude mice and comparable to ras-H-transformed RT-4 when orthotopically onplanted as histologically intact tissue. PMID- 1639545 TI - A new patient-like metastatic model of human lung cancer constructed orthotopically with intact tissue via thoracotomy in immunodeficient mice. PMID- 1639546 TI - Patterns of substance use among students meeting lifetime DSM-II criteria for alcohol misuse. AB - A cross-sectional survey of 989 college students was conducted to investigate substance use patterns between students meeting lifetime DSM-III alcohol misuse criteria and students not meeting misuse criteria. Students meeting alcohol misuse criteria (n = 294) reported a significantly greater history of lifetime substance use and were more likely to have used marijuana in the 6 months prior to the receipt of the questionnaire. No significant differences in the frequency of substance use within the 6-month period were indicated between the two student groups with the exception of marijuana. Students meeting lifetime DSM-III alcohol misuse criteria also reported having experimented with marijuana at an earlier age. PMID- 1639547 TI - Alcohol misuse among college students and other young adults: findings from a general population study in New York State. AB - The predictors of heavier drinking patterns and alcohol-related problems are examined for young adults aged 18 to 25 years by using a large representative sample. The sample includes both college students and noncollege students. Young adult males have the highest rates of alcohol misuse when compared with all other age groups. Beginning to drink at an early age and growing up with a heavy drinking father are strong predictors of both current heavier drinking and alcohol-related problems. For males, the effect of father's heavy drinking is especially strong. Furthermore, living in a dorm as a college student makes a unique contribution to alcohol misuse. PMID- 1639548 TI - Conceptions of alcoholism. AB - Alcoholism educators have assumed that endorsement of the disease concept of alcoholism would reduce the moral stigma associated with the condition, thereby promoting a more humanitarian approach to the alcoholic. The present study presents data relevant to these assumptions. Measures of beliefs about the medical and moral nature of alcoholism were collected from 1,446 work supervisors in federal agencies. Additionally, social acceptance, tolerance of the alcoholic's absenteeism, and charitable responses to the alcoholic were measured. Results indicated that beliefs about the moral character of the alcoholic and beliefs about the medical nature of alcoholism are significant predictors of social acceptance of the alcoholic, tolerance of work behavior of the alcoholic, and a charitable response to the alcoholic. Findings are discussed in terms of the importance of educational efforts aimed at dispelling beliefs about the moral nature of alcoholism. PMID- 1639549 TI - Testing the progressive nature of alcoholism. AB - The authors employed a new data collection methodology to assess Jellinek's progressive model of alcoholism. Data were collected to explore whether (a) symptoms occurred in four distinct phases, one phase following another, as described by Jellinek's model; (b) the phase markers and the phases of the symptom progression follow one another as predicted in the Jellinek model; and (c) the sequence of each of the 46 individual symptoms is as described by a serial interpretation of Jellinek's model. The authors also compared male participants with female participants on the conditions described above. PMID- 1639550 TI - Relations among stressors, strains, and substance use among resident physicians. AB - This study examined the relationship between work-related stress and substance use among resident physicians in the United States. Unlike previous studies of physician stress, this study distinguished between "stressors" (stressful job conditions) and "strains" (reactions to the work environment) and correlated each of these with substance use. Results indicated that relations among stressors, strains, and substance use were not strong. Strains, however, were more strongly related to substance use than stressors. Additionally, benzodiazepines were more strongly related to strains than other substances, suggesting that they may be used for self-treatment. Other implications of these findings and future research needs are discussed. PMID- 1639552 TI - Redecision therapy. AB - Redecision therapy has grown out of an amalgam of transactional analysis and Gestalt therapy along with extensive clinical experience. This approach as developed by the Gouldings presents a model that differs from group-focused therapy in a number of ways. The treatment is centered on the individual. The therapist takes an active role in the treatment and works within the contract for change of each individual. Many of the traditional concepts of group therapy like transference, cohesion, resistance, and group process are not used. The theory of transactional analysis serves as a conceptual core along with terms developed to describe the processes used in redecision therapy. Impasses, contact, cons, games, early decisions, anchoring, injunctions, and scripts are part of the lexicon of this treatment. PMID- 1639551 TI - Resistance to drug offers among college students. AB - This study investigated the social context of drug offers among college students. The communicative processes involved in drug offers and resistance were examined along with drug use history, gender, family income, relationship to offerer, and location of offer. The prevailing pattern was of simple offers followed by simple statements of no, with no continuing pressure by the offerer. However, some form of pressure was reported in almost half of the cases and most frequently resulted from resisting through statements of dislike for product or lack of desire. The least amount of pressure was associated with marijuana offers. PMID- 1639553 TI - The place of self psychology in group psychotherapy: a status report. AB - This article reviews the growing contribution of self psychology to group psychotherapy. The basic self-psychological concepts as they are applied to group dynamics and the treatment process are explored. Transference, countertransference, and self-restitutive patterns are illustrated in a clinical vignette that includes a "difficult" patient's impact upon the interactional and group-as-a-whole processes. Several directions for future investigation are described. PMID- 1639554 TI - Reflections on a developing body of group-as-a-whole theory for children's therapy groups: an introduction. AB - This essay serves as an introduction to a collection of articles on group psychotherapy for children that appears in the following pages. These articles are an outgrowth of a symposium on children's group treatments presented at the 1990 Annual Conference of the American Group Psychotherapy Association. The present author provides a general overview of relevant literature and offers an orientation to the subsequent theoretical and practical integrations. PMID- 1639555 TI - Complementary cultures in children's psychotherapy groups: conflict, coexistence, and convergence in group development. AB - This article presents a model for understanding development within children's psychotherapy groups. It is proposed that two complementary cultures exist within children's groups, one, indigenous peer culture, strictly of the children's making and the other, therapeutic group culture, created by the therapist in collaboration with group members. The therapist is wise to approach indigenous peer culture as an ethnographer might a native culture, with an emphasis on observation and seeking understanding rather than on intervention. The therapist can use the indigenous peer culture to speak to the children in their own language and eventually to engage them in collaboratively building a meaning system that is uniquely designed to address their psychotherapeutic needs. The article defines these concepts, develops them theoretically, and illustrates them clinically. PMID- 1639556 TI - The evolution of culture and cohesion in the group treatment of ego impaired children. AB - The challenge of group treatment with ego impaired children is to provide a situation in which their maladaptive efforts to organize volatile affects and impulses can be tolerated and structured. This article addresses the process of culture building in group and how it can provide a cohesive structure for affective expression that is acceptable and tolerable to the defensive, resistant child. In particular, the author will argue that it is through the sense of normality and commonality engendered by indigenous peer culture that the members initially develop a structure and language for affiliation, play, and mutual identification. By facilitating the cohesion of indigenous peer culture, the therapist creates a sufficient holding environment to begin a dialogue involving both verbal and nonverbal communication. For children who are difficult to engage in discussion, let alone treatment, this dialogue is the essential process for creating a corrective emotional experience. Through a concise case study, the author describes the process by which the children's efforts to express and create their own culture are cultivated, managed, and understood. PMID- 1639557 TI - A world between realities: an exploration of therapeutic group culture and transitional phenomena in a long-term psychotherapy group. AB - In long-term, open-ended psychotherapy groups in which there are inevitable, yet potentially disruptive changes in membership, therapeutic group culture can become particularly important in sustaining a group's sense of cohesion. This article focuses on how transitional phenomena, as defined by D. W. Winnicott, and representational play serve as vehicles for establishing therapeutic group culture in a preadolescent girls' group. Applications of both transitional phenomena and therapeutic group culture to group stage development, as outlined by Garland, Jones, and Kolodny (1970), will also be explored. PMID- 1639558 TI - The establishment of individual and collective competency in children's groups as a prelude to entry into intimacy, disclosure, and bonding. AB - This article offers a theory about the evolution of small group systems through a series of stages. It discusses the relationship of these stages to and their effect on the self-other and therapeutic interventive spheres in the long-term group treatment of children. The developmental unfolding is seen as universal to small groups and as operating on an interpersonal and collective level, distinguishable from individual psyches and close dyadic bonds but influenced by them. On an isomorphic level the group stages contain emotive, cognitive, and interactive themes and processes that parallel and evoke those of the bonding and work processes. As such, the group dynamic provides an enabling matrix and a mirror for the other goings on in the member-therapist encounter. Its pacing and its progressions and regressions appear to correspond with those of the development of the transitional space and therapeutic culture of the group. Like the other articles in the symposium, this one offers specific examples in which the three spheres intersect and are integrated. PMID- 1639559 TI - Inpatient group processes parallel unit dynamics. AB - The authors conducted a quantitative examination of parallels between milieu and therapy group dynamics on a short-term inpatient unit. The Ward Atmosphere Scale was used to assess the milieu, and the Group Climate Questionnaire-S to measure processes in key groups. Assessments were made by patients and staff once each week for 10 months. The authors found clear parallels between ward and therapy group processes. The parallels reflected the impact of patterns utilization of the unit, its treatment philosophy, and the emotional dynamics of its constituents. Examination of these associations also revealed limitations of the treatment setting, clarified the potential impact of particular staff interventions, and demonstrated biases in the rating methods. Study of parallel process on the psychiatric unit is a rich source of information on the nature of inpatient treatment. PMID- 1639560 TI - Points in question. Endangered parasite species. PMID- 1639561 TI - The use of Taylor's power law to describe the aggregated distribution of gastro intestinal nematodes of sheep. AB - The distribution of gastro-intestinal nematodes collected from lambs was investigated using the Taylor's power law index of aggregation beta, which is known to be independent of the mean population size. For 12 out of the 15 nematode species investigated the estimate of beta was not significantly different from 2.0. For these species a logarithmic transformation would stabilize the variance of the distributions prior to further statistical analysis. The remaining species had values of beta which were significantly lower than 2.0. For these species a variance-stabilizing transformation is given by z = x1-beta/2. PMID- 1639562 TI - Detection by allozyme electrophoresis of cryptic species of Hypodontus macropi (Nematoda: Strongyloidea) from macropodid marsupials. AB - Allozyme electrophoresis of 98 Hypodontus macropi from eight different species of hosts using 24 enzymes revealed a complex of at least six sibling species, with 15-50% fixed genetic differences between taxa. Except for the taxon parasitizing Macropus rufus/M. robustus, pairs of parasite taxa were, in each case, sympatric at each locality examined, thus supporting the conclusion that they represent valid species. The existence of a series of host-specific nematode taxa explains many of the inconsistencies noted previously in the host distribution of H. macropi. Comparison of parasite allozyme phenograms with host phylogeny suggests that four of the speciation events could be attributable to cospeciation and two to host switching. A clear case of host switching between M. rufus/M. robustus and M. fuliginosus was found. PMID- 1639563 TI - Fasciola hepatica: free radical generation by peritoneal leukocytes in challenged rodents. AB - Free radical generation by peritoneal leukocytes from hosts able to develop resistance to reinfection with Fasciola hepatica (rats) was compared with that of hosts unable to develop resistance (mice). Free radical generation by rat leukocytes was 3.5 times higher per cell and 30 times higher per animal than radical production by mouse leukocytes. The capacity of peritoneal leukocytes to produce free radicals in response to adult fluke crude antigen was increased by the presence of host plasma and was quantitatively greater in challenged rats than in naive or primary infected rats. This was not the case for mice, in which cells from primary infected animals were equally as responsive as cells from challenged mice. Further experiments revealed that challenge infection in rats apparently caused the in vivo activation of peritoneal leukocytes and increased levels of unidentified factors in plasma and that both of these responses were involved in the initiation of free radical generation in response to F. hepatica. Dramatic increases in the number of eosinophils present in the peritoneal cavities of primary infected and challenged rats (but not mice) were observed but the role of eosinophils in the production of free radicals in response to F. hepatica remains to be determined. PMID- 1639564 TI - Investigations on the protonephridial system of post-larval Gyrocotyle urna and Amphilina foliacea (Cestoda). AB - The gross morphology and ultrastructure of the different parts of the protonephridial system of the monozoic tapeworms Gyrocotyle urna and Amphilina foliacea are described. The terminal cell in both species has numerous cilia which are interconnected and extend into the lumen of the first canal cell. The filtration area is built up from projections of two cells, the terminal cell and the first canal cell. The first canal cell forms a solid hollow cylinder without a cell gap and a desmosome as found in Neodermata other than cestodes and Udonella. In Gyroctyle the nucleus of the first canal cell is located in the wall cytoplasma whereas more distally located ductules of both species have subepithelial cell bodies containing the nuclei. In both taxa the protonephridial canal system is reticulate. In Amphilina the distal canals lack non-terminal ciliary flames, such ciliary tufts can be found in the larger capillaries of Gyrocotyle. The capillary cilia have rootlets and the ultrastructure of the duct wall cytoplasm containing large numbers of vesicles indicates highly active transport processes. The morphology of the protonephridial systems is discussed with regard to the evolution of Neodermata (especially of the Cestoda) and the function of the protonephridial system in cestodes as a probable organ of nutrient distribution. PMID- 1639565 TI - Cross-reactions of sera from Toxocara canis-infected mice with Toxascaris leonina and Ascaris suum antigens. AB - The ELISA method using larval excretory-secretory (E/S) products and homogenized Toxocara canis, Toxascaris leonina and Ascaris suum adult worm extract were used to determine possible cross-reactions in BALB/c and C57BL/10 mice, inoculated with embryonated eggs or adult worm extract of T. canis in single and multiple doses. When we used sera of mice infected with embryonated eggs of T. canis against different heterologous antigens, we observed no cross-reactions in BALB/c mice against A. suum E/S and adult worm extract antigens with a single dose. In multiple doses this was absent too against T. leonina adult worm extract in BALB/c mice, and in both strains against A. suum E/S and adult worm extract. In BALB/c mice inoculated with adult worm extract of T. canis we did not observe cross-reactions with A. suum E/S antigen with both inoculation doses. In the remainder of the experiments, we observed cross-reactions of different intensities. PMID- 1639566 TI - Vaccines against blowfly strike: the effect of adjuvant type on vaccine effectiveness. AB - Vaccination of sheep with a partially purified extract of Lucilia cuprina larvae in some cases resulted in marked reduction of growth in larvae which fed on the sheep. Twelve adjuvants were assessed, in vitro and in vivo, to determine which induced the largest inhibitory effect on larval growth. The Freund's complete adjuvant and Quil A groups produced ELISA antibody levels significantly higher (P less than 0.05) than other groups. Seven adjuvants mediated an immune response which caused significant inhibition of larval growth (P less than 0.05). When the sheep were assessed by in vivo larval culture, only larvae feeding on sheep vaccinated with the antigen presented in Freund's complete adjuvant or dextran sulphate or a dextran sulphate/Freund's incomplete adjuvant mixture weighed significantly less (P less than 0.05) than larvae feeding on control sheep. The effect on larvae was monitored in vitro for 70 days after vaccination, by which time significant reduction in larval weight was no longer observed. The loss of larval growth inhibition was not associated with a corresponding reduction in overall antibody levels. PMID- 1639567 TI - The mortality and fecundity of Haemonchus contortus in parasite-naive and parasite-exposed sheep following single experimental infections. AB - Parasite-exposed lambs and their parasite-naive controls were experimentally infected once only with 30,000 H. contortus larvae at 3, 9, 12, and 20 weeks following termination of a moderate immunizing infection of 30,000 H. contortus larvae. Previously exposed lambs, challenged at 3 weeks, had a significant reduction in the total H. contortus worm burden as compared to parasite-naive controls. No difference in the total H. contortus worm burden was found between parasite-exposed or parasite-naive lambs challenged at 9 weeks or thereafter. Female worms were found to be significantly smaller in lambs previously exposed to the parasite as compared to those found in parasite-naive lambs. The average parasite fecundity was 4700 eggs per female worm per day. Previous exposure of the lambs to the parasite had no effect on parasite fecundity. Various mathematical models were used to examine parasite fecundity. Parasite fecundity was found to increase in the initial post-challenge period reaching a constant value approximately 58 days after challenge infection. No density-dependent constraints on fecundity were observed. PMID- 1639568 TI - Interspecific interactions in naturally acquired nematode communities from sheep abomasum in relation to age of host and season in four areas of Leon (Spain). AB - The abomasa of naturally infected ewes (407) and lambs (190) from four areas of Leon were collected weekly over 2 years in the abattoir of Leon (north-west Spain). The major species and morphs found were Teladorsagia circumcincta and Trichostrongylus axei and to a lesser extent Marshallagia marshalli and Teladorsagia trifurcata. The putative interactions between species were assessed by Euclidian distances based on the results of multivariate analyses. The estimation of interaction was either based on mean intensities of worm burdens or on frequencies of nematode species within individual hosts. The areas, years, seasons and categories of sheep (ewes or lambs) did not influence the interaction estimates. These were not dependent upon the size of worm burden. The majority of interactions were positive. Slight negative interactions were found only with T. circumcincta-T. axei, T. circumcincta-M. marshalli and M. marshalli-T. axei. Positive interactions were recorded between the less frequent species. PMID- 1639569 TI - Viability of Echinococcus granulosus cysts in mice following cultivation in vitro. AB - The viability of hydatid cysts developed in vitro for 90 days was assessed by implantation into mice. Cysts removed from mice at 270 days post-infection (p.i.) increased their size 13.5-fold and contained several brood capsules containing protoscoleces. Thus, cysts remain viable after prolonged in vitro culture. The implantation in mice of 15 cysts developed in vitro yielded an average of 10 cysts per mouse, which is indicative of a high survival rate in these experimental infections. The ultrastructural study of cysts recovered from mice 270 days p.i. showed that the germinal membrane was more compact than before implantation and several layers of tegumental cells had developed. Observations of cysts removed from mice indicated that the plasma membrane surrounding microtriches had prolongations opening into the laminated layer. PMID- 1639570 TI - The role of the fat body, midgut and ovary in vitellogenin production and vitellogenesis in the female tick, Dermacentor variabilis. AB - Polyclonal antibodies directed against D. variabilis vitellin were utilized for immunocytochemistry at the ultrastructural level. We localized vitellogenin (Vg) in rough endoplasmic reticulum cisternae, secretory granules and secreted products of fat body trophocytes and midgut vitellogenic cells from feeding and ovipositing females. Vg was localized in the oocyte Golgi bodies and in the yolk bodies of both feeding and ovipositing females. Uptake of exogenous Vg was indicated by the presence of immunospecific gold probe in coated pits and coated vesicles at the apical plasma membrane of oocytes from females in rapid engorgement and oviposition. In unmated females little detectable evidence of Vg uptake by developing oocytes suggests that mating and host detachment signal the beginning of vitellogenesis. We conclude that fat body trophocytes, midgut vitellogenic cells and oocytes are involved in the synthesis and/or processing of Vg and that feeding is the signal associated with the initiation of Vg synthesis and/or processing. PMID- 1639571 TI - The dynamics of trickle infections with Heligmosomoides polygyrus in syngeneic strains of mice. AB - NIH, CBA, SWR and C57B1/10 mice were repeatedly infected with Heligmosomoides polygyrus, using doses of 10-50 larvae at frequencies of 2-16 days. NIH and SWR mice regulated the worm burdens at a stable dose-dependent level for a period of several weeks, following which expulsion occurred and immunity to subsequent re infection was established. This regulation did not occur in CBA or C57B1/10 mice, and was inhibited by cortisone treatment. Evidence was found to suggest that regulation is the result of an immune response directed against the late larval stages of the parasite, shortly after their emergence into the lumen of the gut. The frequency of infection was an important factor in determining the course of infection. Frequently infected mice expelled the parasites more rapidly than mice infected with the same total number of larvae in fewer less frequent doses. PMID- 1639572 TI - Ultrastructural studies on oocysts, sporulation and sporozoites of Schellackia cf. agamae from the intestine of the starred lizard Agama stellio. AB - Young intracellular oocysts of Schellackia cf. agamae in the gut epithelium of agama stellio were bound by several fine membranes. Later-stage oocysts and sporoblasts in the lamina propria were intercellular and were bound by a thin but firm tri-layered wall. Oocysts had a large central refractile body which, during sporulation, sent extensions into the developing sporozoites. Sporozoites escaped into the gut tissue, leaving a large oocyst residuum with the remains of a refractile body. These sporozoites invaded a variety of connective tissue cells, endothelial cells and circulatory leucocytes in the lamina propria. Sporozoites caused lysis of the host cell cytoplasm at their perimeter and multiple sporozoite infections led to complete degradation of the host cell. PMID- 1639573 TI - Resistance to ivermectin by Haemonchus contortus in goats and calves. AB - Efficacy of ivermectin on susceptible or resistant populations of the parasitic nematode Haemonchus contortus was determined in cattle and goats held in a barn. Goats were each infected with 3000 infective, ivermectin-susceptible or resistant H. contortus larvae on day 0 and reinfected with 2000 infective larvae on day 24. Goats were treated orally with 600 micrograms kg-1 ivermectin on day 31. No significant differences were detected in blood packed cell volume (PCV) or total protein (TP), prepatent period, or epg among the four groups of goats that were each infected with one of four parasite strains (one susceptible, three resistant). There were no differences among the four parasite strains in the numbers of infective larvae that developed to the third larval stage from fecal cultures or in the viability of cultured infective larvae when held in the laboratory at 27 +/- 1 degrees C for 14 weeks. After treatment with ivermectin, there were significant differences among the parasite strains in PCV, TP, and epg. Total worm counts were reduced by 94 to 97% with three times the recommended dose. Immature and adult Skrjabinema ovis were also present in two treated goats. In a second test, one goat infected once with 10,000 infective larvae of a resistant strain of H. contortus and then treated with nine doses of ivermectin, increasing from 500 to 2000 micrograms kg-1 over a period of 133 days, had 35 adult worms at necropsy. In a third test, three calves were readily infected with an ivermectin-resistant strain of H. contortus from goats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639574 TI - No adaptation of Haemonchus contortus to genetically resistant sheep. AB - A composite population of Haemonchus contortus was established with larvae from seven diverse sources, then maintained in Merino sheep bred to have either increased or decreased resistance to Haemonchus. After five, seven and 14 parasite generations, the two resulting lines of parasites were used to infect sheep from the increased resistance line, an unselected control line and the decreased resistance line. Line of sheep had a highly significant effect on average faecal egg counts 4 and 5 weeks after infection (geometric means 329, 735 and 1490 epg, respectively after the 14th generation), but the two lines of parasites yielded similar egg counts. There was no significant interaction between line of sheep and line of parasite, indicating that the parasite populations had not diverged significantly in their reproductive fitness, as measured by faecal egg count. PMID- 1639575 TI - Codon usage in Entamoeba histolytica. AB - The codon usage of 10 E. histolytica genes comprising 4455 codons was analysed. The codon usage revealed an extremely biased use of synonymous codons with a preference for NNU (44%) and NNA (41.4%) codons. Codons CGG (arg), AGG (arg) and CCG (pro) were absent in the E. histolytica genes examined. The codon usage of E. histolytica resembled that of Plasmodium falciparum. PMID- 1639576 TI - Bovine babesiosis: failure to induce interferon gamma production in response to Babesia bovis antigens in cattle. AB - The immune response to Babesia bovis infection or vaccination was evaluated by measuring antibody and interferon gamma (IFN-gamma) production to protective recombinant and crude native B. bovis antigens. Cells from vaccinated or infected cattle failed to produce detectable IFN-gamma when stimulated with B. bovis antigens in vitro. In contrast, antibody was induced by protective recombinant B. bovis antigens. These findings are consistent with the argument that immunity to B. bovis infection is correlated most strongly with humoral rather than cell mediated immune responses. PMID- 1639577 TI - Differential stability of the benzimidazole (BZ)-tubulin complex in BZ-resistant and BZ-susceptible isolates of Haemonchus contortus and Trichostrongylus colubriformis. AB - The binding of [3H]mebendazole ([3H]MBZ) to tubulin from BZ-susceptible (BZ-S) and BZ-resistant (BZ-R) isolates of Haemonchus contortus and Trichostrongylus colubriformis was investigated using charcoal extraction and gel filtration techniques. The amount of [3H]MBZ bound at infinite free ligand concentration (Bmax) was significantly reduced for the BZ-R isolate compared with the BZ-S isolate in both species when assayed by charcoal extraction. However, Bmax was increased to comparable levels for both BZ-S and BZ-R isolates of each species when assayed by the less stringent gel filtration technique. These results indicate that the BZ-tubulin interaction in trichostrongylid nematodes is comprised of a minimum of two components. As similar levels of total [3H]MBZ binding were observed for both BZ-S and BZ-R isolates of each species when assayed by gel filtration, it is suggested that the reduction in the pseudo irreversible BZ binding component in BZ-R isolates results in an increase in the level of reversible BZ binding and therefore provides a survival advantage to BZ R nematodes. PMID- 1639578 TI - Changes in allozyme pattern of the protozoan parasite Giardia intestinalis. AB - The present study compares the allelic profiles of Giardia intestinalis grown in vivo and in vitro. Three clinical isolates of G. intestinalis were established in suckling mice and subsequently adapted to in vitro culture to test the null hypothesis that samples of the same clinical isolate grown in different culture conditions have identical allelic profiles. For each isolate, a mouse-derived and an axenically cultured sample were analysed electrophoretically at 11 enzyme loci. In each case, the axenically cultured sample of each isolate showed marked allelic differences from its corresponding in vivo sample. These data suggest that there may be either regulated expression of alternative genes encoding distinct isozymes (i.e. gene switching) or selection by different growth conditions of specific genotypes from a mixture present within the original clinical isolate. Although these hypotheses are not tested in this study, the data highlight the importance of confirming that allozymes (or isozymes) are stable genetic characters for the identification and characterization of protozoan taxa. PMID- 1639579 TI - The electronic fight against the schistosomes. AB - A DOS-compatible model for use on personal computers has been constructed for teaching in parasite epidemiology. The program is based on the Macdonald model of schistosome dynamics and enables simulation of the effect of a control campaign on a human worm load by reducing four transmission factors in the parasite life cycle: (1) egg contamination, (2) snail lifetime, (3) exposure to cercariae and (4) adult worm lifetime. PMID- 1639580 TI - Collagen as a pharmacological approach in wound healing. AB - The authors have reviewed the most important biological mechanisms involved in wound healing, the main agents that modify the healing process and the physiological and pharmacological role of collagen. Putative mechanisms of collagen in wound repair are described with particular emphasis on haemostatic effect, interaction with platelets and fibronectin, properties of of increasing fluid exudate and its cellular component (macrophages) and the "scaffold" role for fibroblastic proliferation. Experimental and clinical data clearly suggest that the potential use of collagen in wound repair and its main therapeutical applications: treatment chronic leg ulcers and pressure sores, burns, urological surgery, gynaecological surgery, dentistry and oral surgery, reconstructive surgery, abdominal and vascular surgery, orthopaedy. PMID- 1639581 TI - Lyophilized non-denatured type-I collagen (Condress) extracted from bovine Achilles' tendon and suitable for clinical use. AB - On account of the biological role of collagen in wound healing, and because of its biocompatibility, the use of heterologous collagen-based devices is becoming more widespread. Here we describe the extractive procedure and properties of a lyophilized type-I collagen (Condress) suitable for clinical use. Condress is extracted from bovine Achilles' tendon through a non-denaturing procedure in the absence of proteolytic enzymes. It has not been submitted to a chemical cross linking process before lyophilization. Chemical identification of Condress as type-I acid-insoluble collagen has been carried out by evaluation of total nitrogen and hydroxyproline contents and by chromatographic examination. Electrophoretic analysis and morphological examination by electron microscopy confirm that the procedure employed to extract collagen does not alter the polypeptidic composition of the molecule and its structure. A gamma-ray dose between 0.5 and 1.5 Mrad is quite adequate to sterilize the final product and certainly devoid of degradative effect. The finished product has a special (peculiar) absorbing capacity, immersion time, strain resistance, wrinkling temperature and enzymatic digestion time. It is a nonallergenic product suitable for clinical use. When it has been applied in chronic leg ulcers, pressure sores, or reconstructive surgery, Condress seems to substantially improve wound repair. PMID- 1639582 TI - Heterologous collagen in wound healing: a clinical study. AB - The author reports an open controlled trial on 72 patients affected by different types of skin ulcers, in which a heterologous lyophilized collagen sponge was compared with Dextranomer as healing adjuvant. The rationale of use and pharmacological properties of this collagen are outlined and explain its outstanding results. PMID- 1639583 TI - Healing of open skin surfaces with collagen foils. AB - Applications of Condress (patented sheets of pure bovine collagen) on open skin surfaces (30 cases of "ulcus cruris", 5 cases of decubitus, and malum perforans; 10 cases of full-thickness burns) were examined in a controlled trial. Quantification of regeneration speed, macrophotographic survey of granulation tissue and epithelial border, thermographic and chromometric evaluation of the skin microcirculation, and histological observation of regenerating tissues, were the parameters used. The following results were obtained: marked reduction of healing time, different aspects of the granulation-tissue responses, different times of topical collagenolysis, increased vascular perfusion, histological activation of angiogenesis, fibrogenesis, histiomacrophage function and superficial absorption. The employment of Condress in burn areas seems to be highly promising. PMID- 1639584 TI - The use of lyophilized collagen in gynaecology. AB - Collagen plays an important physiological role in the process of wound healing and the possibility of using lyophilized collagen has opened up prospects in surgery. The author reports his experience in gynaecological surgery: myomectomy, vaginal or abdominal hysterectomy and repair surgery for vaginal prolapse with hysterectomy and cystourethropexy. The results obtained suggest the use of lyophilized collagen in the above-mentioned cases and a possible wider application in gynaecological surgery. PMID- 1639585 TI - Heterologous, lyophilized, non-denatured type-I collagen in dentistry. AB - Experience in the use of a heterologous collagen, extracted from bovine Achilles' tendon by a non-denaturing procedure, is reported. Normal tooth extraction procedures, periodontal surgery, treatment of alveolitis, oroparanasal communications and maxillary cysts, and oral surgery in patients affected by a defective haemostatic mechanism, benefit from its use. PMID- 1639587 TI - Europe: AIDS nurses join forces. PMID- 1639586 TI - Potential role of heterologous collagen in promoting cutaneous wound repair in rats. AB - The effect of native bovine tendon type-I collagen sponges (CONDRESS) on wound repair was evaluated by employing an experimental animal (rat) model which utilized subcutaneously implanted collagen and polyurethane sponges. Lesions were also created in the control groups with the exception that implants were omitted. The fusion of the hypodermal layer was selected as the index of wound repair expressed as % healing. In order to assess the extent of the healing process, parameters of clinical evaluation such as exudate volume, number of polymorphonuclears (PMNs) and macrophages (MOs) were also determined. All studies were effected at time intervals of 24, 48 and 72 h post wounding and implantation. The collagen-treated groups showed a greater healing capacity as compared to the polyurethane sponge-treated and control groups. Likewise, the exudate volume, number of leukocytes and mononuclear-type cells were all significantly higher for the collagen-treated animals than those of the polyurethane sponge-treated and control ones. Furthermore, the healthier appearance of the artificially produced wounds in the collagen sponge-treated groups (when compared to the others after 24 h) further confirmed collagen's validity in the treatment of wounds. PMID- 1639588 TI - Hepatitis B: a major human cancer. PMID- 1639589 TI - Sharing the challenge: mobilizing nurses against HIV/AIDS in Africa. AB - For two years ICN implemented a WHO/GPA-funded project in Africa to increase the capability and effectiveness of selected national nurses' associations (NNAs) to participate in their countries' campaigns to prevent HIV transmission; reduce the impact of HIV/AIDS on individuals, families and communities; and decrease morbidity and mortality associated with HIV/AIDS. The results have been gratifying. Not only have the nurses from the participating NNAs become a force to be reckoned with in their countries' HIV/AIDS efforts but they have activated major changes in nursing practice and in the delivery of care. Serving as role models, these nurses (numbering over 800) are mobilizing not only their colleagues but all others involved in caring for persons with AIDS. PMID- 1639590 TI - Linking primary health care and self-care through case management. AB - Primary health care (PHC) strategies have heightened health care providers' awareness of the need to understand their communities and provided knowledge on how to mobilize communities for health. Orem, a nurse theorist, has developed a similar philosophical position on mobilizing individuals for self-care, which complements PHC theory at the community level. This article links the philosophies and strategies of PHC with self-are and proposes a delivery model of case management, drawing on examples from the HIV/AIDS pandemic and the aging population to illustrate the type of coordinating activities required of case managers in the 21st century. PMID- 1639592 TI - Orbital disease. PMID- 1639591 TI - Nurses' role in promoting the health of the elderly. AB - Professional nurses have taken a leading role in promoting health of the older adult through a variety of innovative programmes. Among the most important worldwide are in the areas of nutrition; safety; physical, mental, and economic health; and access to services. Some of the major issues and nursing care strategies in each of these areas are described below. PMID- 1639593 TI - Advances in orbital imaging. PMID- 1639594 TI - Periorbital intraosseous hemangiomas. AB - Periorbital intraosseous hemangiomas are a rare clinical entity that may present with visual or cosmetic disturbances. They may be difficult to distinguish from other bony lesions such as malignant metastases. If the diagnosis of hemangioma can be confidently made in a mildly symptomatic patient, the lesion may be observed. In patients in whom the diagnosis is uncertain or when there is visual compromise such as optic nerve compression, total surgical excision is recommended. Preoperative evaluation with angiography should be strongly considered, particularly if embolization can be accomplished prior to surgery. Even then, the surgeon and the patient must be prepared for the risk of significant hemorrhage. PMID- 1639595 TI - Ocular motility disorders and orbital trauma. PMID- 1639596 TI - Correction of enophthalmos with porous polyethylene implants. PMID- 1639597 TI - Correction of telecanthus in the blepharophimosis syndrome. PMID- 1639598 TI - Prophylactic use of antibiotics in oculoplastic surgery. PMID- 1639599 TI - Optic nerve sheath decompression: a review. PMID- 1639600 TI - Update on laboratory tests for diagnosis of orbital disease. PMID- 1639601 TI - Special laboratory methods for pathological diagnosis of orbital disease. PMID- 1639602 TI - The spectrum of orbital vascular disease. PMID- 1639603 TI - Management of lesions at the cranioorbital junction. PMID- 1639604 TI - Treatment options for periorbital hemangioma of infancy. PMID- 1639605 TI - Reconstruction of degenerate rd mouse retina by transplantation of transgenic photoreceptors. AB - Photoreceptors from neonatal transgenic mice with normally developing retinas were transplanted to the subretinal spaces of 2-3-month-old rd mutant mice that lack photoreceptors. The transgenic mouse photoreceptors express high levels of the lac Z reporter gene product, beta-galactosidase, which facilitated tracking the transplanted cells. Two sources were used for these cells: (1) dissection of retinal microaggregates containing photoreceptors and (2) papain-dissociated photoreceptors. Host retinas were examined after transplantation. Both methods led to survival of photoreceptors for at least 2 mo after transplantation. Relatively mature outer segments were found only in transplanted microaggregates; this occurred optimally when the cells were adjacent to the retinal pigment epithelium (RPE). beta-galactosidase-labeled outer segments associated closely with the apical processes of the host RPE, which, together with labeled phagosomes in the RPE cells, suggested functional interaction between the transplanted photoreceptors and the host RPE. This study is the first to the authors' knowledge to show electron microscopically that a morphologically normal appearing photoreceptor layer can be reconstructed in an otherwise photoreceptorless retina. PMID- 1639606 TI - Cultured Muller cells have high levels of epidermal growth factor receptors. AB - High levels of epidermal growth factor (EGF)-receptors have been reported in membrane homogenates of bovine retinas, but the biologic function and tissue target of EGF in the retina have not been established fully. Because EGF participation has been suggested in the mechanisms of wound healing and Muller cells undergo changes after retinal injury, the authors studied EGF receptor expression and functional role of this substance in cultured Muller cells. These cells (isolated from normal rats) were tested for the glial cell markers: vimentin, S-100 protein, and carbonic anhydrase C. These markers were found to be positive through all passages used in the experiments. The 125I-EGF binding in Muller cells was highly specific, concentration dependent, and saturable. Compared with 3T3 fibroblasts, Muller cells bound threefold more EGF. Binding kinetics and Scatchard analyses showed the higher level of binding was related to the greater number of receptors on these cells (Muller cells, 2.4 x 10(5) receptors/cell; 3T3 fibroblasts, 7.1 x 10(4) receptors/cell) rather than a change in affinity of the receptors to bind the ligand. Nonlinear-regression analyses suggested the presence of two classes of affinity sites. The high level of EGF receptor expression in Muller cells was confirmed by western blot analyses that showed increased reactivity of the approximately 170-kilodalton receptor band to a monoclonal anti-EGF receptor antibody. Moreover, EGF treatment of Muller cells resulted in two- to threefold increase in DNA synthesis, as evidenced by 3H thymidine uptake studies. These findings support a functional role for EGF in Muller cell proliferation in retinal disease. PMID- 1639607 TI - The directional reflectance of the retinal nerve fiber layer of the toad. AB - Various optical methods for assessing the retinal nerve fiber layer (RNFL) depend on reflected light, but little is known about the characteristics of the RNFL as a reflecting structure. The authors investigated the angular dependence of light reflected by the unmyelinated nerve fibers of the toad eyecup using a small 500 nm light source that could illuminate the retina from various directions and a movable low-power microscope that imaged the retina onto a cooled charge-coupled device in a digital camera system. Measured areas had nerve fiber bundles separated by gaps. Therefore, the reflectance of a bundle alone could be determined from the difference in intensity between the bundle and an adjacent gap. The RNFL reflectance showed striking directional dependence; nerve fiber bundles seen when illuminated from one direction disappeared completely when illuminated from another. Light reflected by a bundle was confined to a conical sheet concentric with the axis of the bundle. The apex angle of the cone was twice the angle between the incident light and the bundle axis, and the orientation of the cone changed with the orientation of the RNFL. This behavior was consistent with the theory of light scattering by cylinders. Therefore, it was concluded that the RNFL reflectance arises from cylindric structures. These results have clinical significance for imaging the RNFL in the human eye because the apparent intensity of the RNFL will depend, not just on its thickness, but also on its orientation relative to the imaging system. PMID- 1639608 TI - Reduced phagosomal content of the retinal pigment epithelium in response to retinoid deprivation. AB - Previous investigations have shown that lipofuscin accumulation in the retinal pigment epithelium (RPE) is reduced greatly as a consequence of vitamin A deprivation. The mechanism by which vitamin A regulates RPE lipofuscin deposition remains to be determined. It is possible that retinoids are direct precursors of this substance. Alternatively, vitamin A deficiency may reduce the uptake and processing of other potential precursors. In retinas lacking photoreceptor cells, RPE lipofuscin accumulation is decreased substantially. This finding suggested that components of phagocytosed photoreceptor outer segments may be precursors for RPE lipofuscin. The effect of vitamin A deprivation on RPE lipofuscin content therefore could be the result of reduced outer segment phagocytosis by the RPE of vitamin A-deprived animals. To evaluate this possibility, experiments were conducted to determine whether vitamin A deprivation altered the phagosomal content of the RPE. Rats were fed diets containing or lacking retinoid precursors of 11-cis retinal. Retinoic acid was included in the diets of the vitamin A deprived animals. After both 10 and 26 weeks, the RPE phagosomal contents were determined in animals from each dietary group. Photoreceptor cell densities also were measured in these rats. At both time points, the RPE phagosomal content was lower significantly in the retinoid-deprived animals than in those fed a vitamin A precursor of the visual pigment chromophore. This reduction was not the result of photoreceptor cell death; the density of these cells was not affected significantly by dietary vitamin A. Thus, it appears that retinoid deprivation reduces the rate of photoreceptor outer segment turnover and, consequently, outer segment phagocytosis by the RPE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639609 TI - Human retinal pigment epithelial cells cultured in hyperglycemic media accumulate increased amounts of glycosaminoglycan precursors. AB - Confluent human retinal pigmented epithelial cells were cultured on microcarrier beads in the presence of 5.6 or 26 mmol/l glucose with or without the aldose reductase inhibitor Sorbinil (200 microM) for 2 wk. At the end of the incubation period, perchloric acid extracts were prepared and analyzed by 31P nuclear magnetic resonance spectroscopy. As assessed by this method, the phosphorylated metabolites of cells incubated with 5.6 or 26 mmol/l glucose differed significantly in the concentrations of a number of uridine diphosphate (UDP) conjugated monosaccharides, which were elevated two- to threefold in cells incubated in 26 mmol/l glucose over control samples. The affected metabolites were identified (through a series of spiking experiments) to be UDP-N acetylglucosamine, UDP-N-acetylgalactosamine, and UDP-glucuronic acid. Coincubation of the cells with Sorbinil 200 microM in the presence of 26 mmol/l glucose had no effect on this accumulation. Under normal circumstances, these molecules selectively and sequentially are incorporated into the polysaccharide chains of glycosaminoglycans (GAGs), whose presence and distribution in the basement membranes is affected adversely by diabetes mellitus. These data suggest that the availability of the monosaccharide precursor is not the rate-limiting step for GAG synthesis in the presence of pathologic glucose concentrations. Thus, the lost GAG content in the basement membranes of diabetic patients may be caused by changes elsewhere in the biosynthesis and/or catabolism of the polysaccharide-linked protein molecules. PMID- 1639610 TI - Ethacrynic acid induces reversible shape and cytoskeletal changes in cultured cells. AB - Cell cultures derived from trabecular meshworks of human and bovine eyes and from bovine vascular endothelia were incubated at 37 degrees C for 1 hr with ethacrynic acid (ECA, 0.1-0.5 mmol/l) dissolved in culture medium. At 2 hr after the initial exposure, ECA at concentrations up to 0.4 mmol/l induced a reversible alteration in cell shape in all three cell types that was coincident with a change in the staining pattern of major cytoskeletal components including actin, alpha-actinin, vinculin, and vimentin. Distinct progressive alterations in beta tubulin also occurred, with initial changes observed 10 min after ECA exposure. The ECA-induced changes in tubulin were blocked in part by preincubation with taxol (which stabilizes the microtubule structure), but they appeared to differ from those occurring with nocodazole (which interferes with tubulin assembly). These results suggest the possibility that ECA-induced increases in outflow facility may be mediated by alterations in the cytoskeletons of outflow pathway cells. PMID- 1639611 TI - Immunomodulation of experimental autoimmune uveoretinitis by intravenous injection of uveitogenic peptides. AB - Intravenous (IV) injection of antigenic proteins induces specific unresponsiveness, as shown by the diminished response to a challenge with these proteins in complete Freund's adjuvant. This study examined the effect of IV treatment with uveitogenic peptides on the development of experimental autoimmune uveoretinitis (EAU). The peptides used were derived from the sequence of bovine interphotoreceptor retinoid-binding protein (IRBP) and included R16 (sequence, 1177-1191), which is immunodominant and highly uveitogenic, and R4 (sequence, 1158-1180), which is nondominant and weakly uveitogenic. The efficacy of this treatment was found to depend on both the dose used for the IV injection and that used for the challenge. Thus, EAU induced by R16 at a dose of 0.2 nmol/rat was inhibited completely in all rats treated with the peptide at doses of 400 or 133 nmol and partially by the low dose of 5 nmol/rat. However, the EAU induced by a R16 challenge of 40 nmol/rat was inhibited only partially by the high treatment dose of 400 nmol/rat. The IV treatment was found to be effective in inhibiting the EAU induced by peptide R4. A large dose of R4 was needed to induce EAU (40 nmol/rat), and the disease was inhibited completely in all rats treated IV with this peptide at doses of 800, 400, or 133 nmol. In most animals injected with the 44-nmol dose, also, inhibition was complete. These data show that there is a correlation between the doses needed for achieving inhibition and those used for the challenge. The ratios between these doses in all experiments were found within the range 1-20.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639612 TI - Immune response to Staphylococcus epidermidis-induced endophthalmitis in a rabbit model. AB - Although Staphylococcus epidermidis is the most common cause of postoperative pseudophakic endophthalmitis, little is known about the immune response to S. epidermidis-induced endophthalmitis. Using a rabbit model, the immune response to an intravitreal injection of 7000 S. epidermidis (group 1) or 30,000 S. epidermidis (group 2) organisms was investigated. Clinical evaluations showed that rabbits in group 2 had a more severe inflammatory reaction in the conjunctiva, cornea, iris, and vitreous than those in group 1. The inflammatory reaction in group 1 largely resolved by day 30; group 2 continued to show a severe inflammatory response. Histopathologic findings correlated with clinical findings, with rabbits in group 2 showing a more severe inflammatory reaction in both the anterior and posterior segments of the globe. Positive vitreous cultures for S. epidermidis were present in rabbits in group 1 on days 3, 7, 10, 14, and 21 but not thereafter. However, group 2 had higher vitreous colony counts at days 3, 7, and 14 and negative vitreous cultures thereafter. Neither group showed delayed hypersensitivity to S. epidermidis antigens (evaluated by skin tests). Serum immunoglobulin (Ig) G antibody levels to phenol-inactivated S. epidermidis and glycerol teichoic acid (GTA) increased progressively, reached a peak at days 10-14, and then declined in both groups. Serum IgA antibody levels to these antigens were not detected. Group 2 had a more prolonged IgG antibody response in vitreous and aqueous than group 1. Tear fluid showed the weakest IgG and IgA antibody response to S. epidermidis and GTA. S. epidermidis-induced endophthalmitis was associated with a humoral but not a delayed hypersensitivity response to this organism. PMID- 1639613 TI - Ultrastructural changes of human trabecular meshwork after photocoagulation with a diode laser. AB - A diode laser, which emitted infrared radiation at a wavelength of 810 nm, was used to perform trabecular photocoagulation in a human eye due for enucleation for malignant melanoma. For comparison, burns were applied with an argon blue green laser (488-514.5 nm). With each laser, the treatment spot size was 100 microns and the pulse duration was 0.20 sec. Visible lesions were produced with a power of between 750 mW and 1.2 W with the diode laser, and 500-900 mW with the argon laser. The pattern of damage produced by both modalities was similar and essentially consisted of contraction or expansion of trabecular beams, with trabecular destruction occurring only in relation to high power exposures. These findings confirm that trabecular photocoagulation is not a process that depends upon the wavelength of the incident energy at the two spectral extremes of 488 nm and 810 nm. PMID- 1639614 TI - Propagation of ciliary smooth muscle cells in vitro and effects of prostaglandin F2 alpha on calcium efflux. AB - The effect of prostaglandin F2 alpha (PGF2 alpha) on calcium efflux from ciliary smooth muscle cells was studied. Ciliary smooth muscle cells, cultured from human ciliary muscle explants, retained the morphologic and immunologic characteristics of smooth muscle cells. High concentrations (to 10(-6) mol/l) of PGF2 alpha were associated with a dose-dependent increase of calcium (45Ca) efflux, whereas at concentrations lower than 10(-8) mol/l there was little or no 45Ca efflux. Our in vitro data are inconsistent with the experimental hypothesis that PGF2 alpha at pharmacologic concentrations relaxes ciliary muscle with a consequent increase in uveoscleral outflow. PMID- 1639615 TI - Urokinase-type plasminogen activator in human aqueous humor. AB - In the anterior segment of the eye, fibrin clots must be rapidly resorbed to prevent further fibrosis and scarring. The aqueous humor of patients undergoing cataract surgery was analyzed for the presence of components of the fibrinolytic cascade. In 30 patients, aqueous humor and plasma were compared for their content of urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), plasminogen activators inhibitors (PAIs), plasminogen, and total proteins. With gel electrophoresis and zymographic assays of serial dilutions of plasma and aqueous humor, all these components were found to be present at lower concentrations in aqueous humor than in plasma. For total proteins, the aqueous/plasma ratio was approximately 0.003, and for plasminogen it was 0.001. Interestingly, the aqueous/plasma ratio for uPA was not as low and varied from 0.01 to 0.03. A significant proportion of the uPA in aqueous humor was present in the two-chain active form. In addition to uPA, aqueous humor contained lower levels of tPA, but no detectable levels of reactive plasminogen activators inhibitors (PAIs). The presence of a relatively high concentration of active uPA shows that the proteolytic balance of the aqueous humor in the anterior chamber of the eye is shifted toward fibrinolysis. PMID- 1639616 TI - Reciprocal corneal transplantation fails to correct mucopolysaccharidosis VI corneal storage. AB - This report contains the results of studies designed to evaluate corneal clearing in mucopolysaccharidosis VI (MPS VI)-affected cats. Corneal buttons from affected cats were transplanted into normal cat corneas and, as controls, normal-to-normal and normal-to-affected transplants also were done. No clearing of the MPS VI graft or host beds occurred, nor was there any clouding of the normal donor or recipient corneal tissues. This assessment was made by serial clinical examinations over a 14-30 mo period and by light and electron microscopic examination of the corneal tissues at the end of the study. Lack of corneal clearing under conditions that would maximize such a process in this animal model indicates that corneal clearing is not an appropriate index for measuring the success of systemic therapy in MPS VI. PMID- 1639618 TI - Visual acuities and scotomas after one week levodopa administration in human amblyopia. AB - The authors previously showed that a single dose of levodopa improves the contrast sensitivity and decreases the size of fixation point scotomas in amblyopic patients. In the present study, they investigated the effect of levodopa after 1 wk of daily administration using a cross-over, double masked design. The decrease of fixation point scotomas was confirmed with automatic static perimetry. An improvement of visual acuity occurred in 70% of the patients after 1 wk of levodopa administration compared to only 22% in the authors' previous study using one single dose. The improvements in visual acuities and visual fields persisted even after the levodopa administration was completed. PMID- 1639617 TI - Regulation of HLA class II antigen expression on cultured corneal epithelium by interferon-gamma. AB - The effect of recombinant human interferon gamma (IFN-gamma) on the induction of HLA class II (HLA-DR, -DP, -DQ) antigen expression on human corneal epithelial (HCE) cells was examined in different stages of culture. Primary cultures were established with limbal explants without endothelium. HCE cells in Stage 1 and Stage 2, with cells negative and positive for the 64K corneal keratin (the marker for advanced corneal epithelial differentiation), respectively, were prepared. HCE cells in both stages were treated with IFN-gamma at a concentration of 0 to 1000 U/ml for two to six days and were stained by the avidin-biotin peroxidase complex method. Class II antigens were not detected on HCE cells in either stage without IFN-gamma treatment. IFN-gamma induced three class II antigens on HCE cells in both stages in a dose- and time-dependent manner but at different levels for each antigen (DR greater than DP greater than DQ). In addition, DQ expression was related to cell differentiation, with DQ extremely rare at Stage 1 and more frequent at Stage 2 (5% vs. 20%). These findings indicate that the induction of class II antigens on HCE cells may be regulated by IFN-gamma independently for each of the antigens and that DQ induction may depend upon the differentiation of HCE cells in culture. PMID- 1639619 TI - The lateral geniculate nucleus in human strabismic amblyopia. AB - Cell shrinkage in monkey lateral geniculate nucleus (LGN) layers supplied by the amblyopic eye have been described in experimental amblyopia caused by visual deprivation, anisometropia, and strabismus. A human brain from a strabismic amblyope became available for study and the authors compared cell sizes in LGN layers receiving input from the normal and the amblyopic eye. Significant cell shrinkage was present in layers connected with the amblyopic eye, and was most evident in the ipsilateral LGN. These findings support the validity of the monkey model for the study of strabismic amblyopia by showing, for the first time, changes in the brain from a human strabismic amblyope that are similar to those previously described in monkeys. PMID- 1639620 TI - Lateral phoria at distance: contributions of accommodation. AB - Lateral heterophoria at distance often is cited as an index of tonic vergence, yet recent research has shown that vergence in darkness is more convergent than most measures of phoria. Two experiments were conducted to investigate the possible role of accommodation in this discrepancy. Experiment I compared measures of distance phoria of 19 young adults with measures of vergence and accommodation of the same subjects. Dark vergence was found to be correlated with but significantly more convergent than distance phoria. Hierarchical regression analysis showed that individual measures of phoria were related to subjects' negative accommodation (from the dark focus to the distant target) as well as to dark vergence. Experiment II tested 13 young adults to evaluate three simple models of the influence of accommodation on distance phoria. Distance phoria was predicted best by a model that included the subjects' negative accommodation, accommodative vergence, and dark vergence. These findings support the hypothesis that distance phoria is influenced by accommodation for the fixation target. Dark vergence is a simpler index of tonic vergence. PMID- 1639621 TI - Visual accommodation and sustained visual resolution in multiple sclerosis. AB - Many multiple sclerosis (MS) patients frequently experience transient blurring. We investigated the possibility that this symptom is due to the inability of patients to sustain an accommodative response to stimuli viewed at distances nearer than or farther from the individual tonus position of accommodation. In a group of MS patients and age-matched healthy control subjects, we measured (1) accommodative range and tonus position; (2) reaction time (RT) to detect a change in a small optotype (viewed in a Badal lens system) as a function of viewing distance; and (3) contrast sensitivity at a fixed viewing distance. MS patients did not differ significantly from healthy controls on near point, far point, pupil size, accommodative range, or tonus position measures. However, as a group, MS patients showed significantly slower RTs than controls to detect optotype changes for stimuli viewed at distances nearer to or farther from the individual tonus position of accommodation. All subjects showed significantly slower RTs to detect changes in optotypes viewed at extreme near and far optical distances compared to RTs to detect changes in stimuli viewed at the tonus position. This difference was significantly larger for MS patients than for controls. These data also suggest that dynamic dioptric factors contribute to the magnitude of contrast sensitivity deficits in this patient population and indicate that the relationship between the individual tonus accommodation position and viewing distance is an important variable in CS testing. PMID- 1639623 TI - Establishing an in-house service program--a case study. PMID- 1639622 TI - Calculation of the pulsatile ocular blood flow. AB - Based on reasonable assumptions, it is theoretically possible to determine the pulsatile ocular blood flow. The pertinent parameter is not the pulse amplitude but the steepest decay value of record (ie, the minimum of dV(t)/dt). Some advantages of developing the record in Fourier series are discussed. The importance of careful analysis of the recording system is stressed. PMID- 1639624 TI - Radiologic quality control and servicing. PMID- 1639625 TI - In-house servicing of x-ray and CT equipment. PMID- 1639626 TI - Job description for x-ray and CT equipment technicians. PMID- 1639627 TI - Birtcher 4400 electrosurgical units and 6400 argon beam coagulation systems. PMID- 1639628 TI - Overheating of replacement batteries in Physio-Control Lifepak 6, 6s, and 7 defibrillator/monitors. PMID- 1639629 TI - T-cell recognition of class II products that result from the combined presence of two different HLA haplotypes. AB - To analyze DR2 haplotypes as recognized by alloreactive T cells, lymphocytes from a DR7; DQw2 homozygous donor were cocultured with irradiated lymphocytes that were DRw15, DR7; DQw6, DQw2 heterozygous. In this report, we focus on two HLA-DQ specific T-cell clones obtained from this priming. These two clones (c3518 and c3523) responded to the positive control (original stimulator) and five of 66 panel donors. Three of these donors typed DRw15, DR7; DQw6, DQw2, as did the positive control. One stimulatory donor typed DRw15, DR7; DQw6, DQw9 and one stimulatory donor typed DRw14, DR7; DQw5, DQw2. Oligonucleotide typing revealed that recognition by the clones depended on the simultaneous presence of the DQB1*0602 gene on one haplotype and DRB1*0701 or DQA*0201 on the other. The hypothesis that c3518 and c3523 recognize an HLA class II product that results from the combination of two different HLA haplotypes was further confirmed in family studies. In three families, it was shown that the DRw15, DR7; DQw6, (DQw2 or DQw9)-positive individuals were recognized, whereas the cells carrying either DRw15; DQw6, DR7; DQw2, or DR7; DQw9 were nonstimulatory. Our results can be explained in two ways: (a) the T cells recognize a class II dimer that results from trans-complementation of DQA1*0101 and DQB1*0602, and (2) the T cells recognize a DR7-derived peptide that is presented by DQw6. PMID- 1639630 TI - T-cell responses against products of oncogenes: generation and characterization of human T-cell clones specific for p21 ras-derived synthetic peptides. AB - Peptides derived from mutated human proto-oncogenes bound to HLA may represent a novel type of tumor-specific antigen. Mutated ras genes are the oncogenes most frequently identified in human cancer. The transforming genes carry a mutation in codons 12, 13, or 61. We have investigated whether the T-cell repertoire of healthy individuals contains T cells capable of recognizing and responding to oncogene-derived peptides. Synthetic peptides derived from mutated p21 ras proto oncogenes, covering mutations at codons 12 or 13 were selected. It was feasible to elicit T-cell responses and isolate several new T-cell clones (TCC) with specificity for a number of different mutated ras peptides after repeated in vitro immunization. Four TCC were characterized with respect to fine specificity and HLA restriction. TCC B and I were restricted by HLA-DR molecules, and recognized the mutated p21 ras-derived peptide carrying Arg and Lys at residue 12, respectively. TCC E and F were restricted by HLA-DQ molecules, the former being specific for a mutated p21 ras-derived peptide with Val in position 13 and the latter more broadly reactive. Peptide competition experiments with a panel of ten peptides derived from p21 ras indicated that all could bind to HLA-DQ molecules of the T-cell donor, while several were also able to bind his HLA-DR molecules. These results show that several p21 ras mutations resulting in aa substitutions at residues 12 or 13 could be recognized by T cells derived from precursor T cells of relatively low frequency present in the normal repertoire of a single donor. PMID- 1639631 TI - Linkage between HLA-DRB1 and -DRB3 types in the Japanese population analyzed by oligonucleotide genotyping. AB - We analyzed linkage between HLA-DRB1 and -DRB3 types in 219 Japanese donors by oligonucleotide genotyping. In the Japanese population, DRB1*1201 was linked with DRB3*0101 in all donors analyzed; in contrast, most Caucasian DRB1*1201 is known to be linked with DRB3*02(01/02) (*0201 or *0202). However, most DRB1*1202 was linked with DRB3*0301. Thus, the two DRw12-related DRB1 types are linked with DRB3 types distinct from each other. All the three DRw14-related DRB1 types, DRB1*1401, DRB1*1402, and DRB1*1405, were linked with DRB3*02(01/02) in the Japanese population, contrasting with the known linkage between DRB1*1402 and DRB3*0101 in other ethnic populations. The serologically "blank" DR type, DRB1*1403, was linked with DRB3*0101. Other DRB1 types, DRB1*0301, DRB1*11(01/04) (*1101 or *1104), and DRB1*13(01/02) (*1301 or *1302) in the Japanese population were linked mostly with the same DRB3 types, like those known in other ethnic populations. PMID- 1639632 TI - HLA-DR expression in human fetal thymocytes. AB - We analyzed the expression of MHC class I (W6/32) and class II (HLA-DR) antigens on human fetal and postnatal thymocytes by fluorescence-activated cell sorting. Less than 5% of prenatal thymocytes expressed HLA-DR before week 12 of gestation. However, the number of HLA-DR-positive cells significantly increased during the late second and third trimester of gestation, when greater than 50% of prenatal thymocytes expressed HLA-DR. Such high-level expressions of HLA-DR in fetal thymocytes were also demonstrated by Northern-blot analysis and immunohistochemistry. After birth, the percentage of HLA-DR-positive cells in thymocytes decreased gradually. A high-level expression of class I antigen was also observed in thymocytes from the early stages of gestation, but, in contrast to MHC class II, a majority of postnatal thymocytes maintained high levels of class I antigen after birth. PMID- 1639633 TI - Blood flow and steady state temperatures in deep-seated tumors and normal tissues. AB - Blood flow related data obtained in different deep-seated tumors and adjacent normal tissues were analyzed in 28 patients who were treated with combined regional hyperthermia and radiation for recurrent or metastatic tumors. The evaluation of blood flow related data has been made using the thermal clearance/thermal cooling coefficient technique and dynamic computed tomography. With both methods significant differences in global perfusion have been observed between tumor center and tumor periphery, between tumor and normal tissue (deep muscle and fat tissue), and between tumor entities. Washout rates or thermal cooling coefficient values, as well as the enhancement of contrast material over baseline (expressed in delta Hounsfield Units), correlated significantly with the achieved steady state temperatures for different tissue categories (i.e., tumor center, tumor periphery, different tumor entities, normal tissue). Thermal cooling coefficient values higher than 63000-83000 W/m3-K (washout rates higher than 15-20 ml/100 g-min) or values of enhancement of contrast material higher than delta 20-25 HU coincide with a limitation in achieving therapeutic temperatures higher than 40 degrees C. PMID- 1639634 TI - Feasibility of estimating the temperature distribution in a tumor heated by a waveguide applicator. AB - The feasibility of using a 2-dimensional (2D) modeling approach for retrospectively describing complete temperature distributions in the midplane of a tumor during a clinical hyperthermia treatment was tested. An experimental treatment, using a 915-MHz waveguide applicator to heat a large melanoma in a dog, was modeled. Detailed measurements of temperatures were made during the treatment. The steady-state blood flow distribution at the midplane was imaged by positron emission tomography (PET), and these data were used to prescribe the modeled perfusion pattern. A 2D finite element method (FEM) was used to approximate the solution to Maxwell's Equations to obtain the specific absorption rate (SAR) distribution. The blood-flow estimates, assumed material properties, SAR distribution, and temperature boundary conditions were then used with the same mesh in a second FEM program to obtain a solution to the bioheat transfer equation. This latter routine was embedded in a state-and-parameter-estimation program that systematically varied selected parameters until the differences between computed and measured temperatures were minimized. Optimizations were performed independently for three subsets of the measured temperature data to assess the sensitivity of the predicted temperature field to the number of measurements. The calculated temperature distributions that resulted were similar to each other, and the predicted temperatures at the sensor points excluded from these optimizations were in reasonable agreement with the measurements. However, lack of unique blood flow values following optimization indicates that the methods of estimating blood flow will need to be improved or that there are problems with model mismatch. This work is a clinical case study of an evolving 2D system of thermal dosimetry which relies on both empirical and theoretical concepts. The methodology is being evaluated for its ability to generate prognostically significant descriptors of the treatment temperature field. PMID- 1639635 TI - Post-mastectomy radiotherapy following adjuvant chemotherapy and autologous bone marrow transplantation for breast cancer patients with greater than or equal to 10 positive axillary lymph nodes. Cancer and Leukemia Group B. AB - Between 2/87 and 2/91, 49 women with operable breast cancer involving greater than or equal to 10 axillary nodes were treated following mastectomy, with four cycles of Cyclophosphamide, Adriamycin, 5FU, followed by high doses of Cyclophosphamide, Cisplatin, Carmustine (HDCT) with autologous bone marrow transplant support. Forty patients received local-regional radiotherapy (generally to the chest wall, internal mammary, supraclavicular, +/- axillary nodal areas; minimum 44-50 Gy, 1.8-2 Gy/fraction, +/- 10-15 Gy scar boost; standard radiation techniques). The first nine patients did not receive local regional radiotherapy. Three developed a local-regional failure (6-12 months after HDCT); six are without evidence of disease. Local-regional radiotherapy (LR XRT) was delivered to the subsequent 40 patients following HDCT+autologous bone marrow transplant. Six received less than 44 Gy of the planned local-regional radiotherapy due to significant toxicity and one of these failed locally. Only one local failure was observed among the 34 patients who received greater than or equal to 44 Gy. Two additional patients developed distant metastases. None of these 40 patients have failed in the axilla despite the fact that the axilla was irradiated in only 18 cases. Overall, 36/40 (90%) of these patients are without evidence of disease 4-30 months following HDCT (approximately 10-36 months after mastectomy, median 22 months). Radiotherapy was interrupted or discontinued because of progressive dyspnea, thrombocytopenia, or neutropenia in nine patients. Further studies to determine the roles of local-regional radiotherapy and HDCT in the development of these toxicities are underway. These encouraging results suggest that HDCT + autologous bone marrow transplant+local-regional radiotherapy may improve the survival rate in these high risk patients. A national randomized study to test the efficacy of this HDCT regimen is currently underway (Cancer and Leukemia Group B#9082 and Southwest Oncology Group #9114). PMID- 1639636 TI - Marrow transplantation following escalating doses of fractionated total body irradiation and cyclophosphamide--a phase I trial. AB - Thirty-six patients with advanced hematologic malignancy were entered into a Phase I study designed to define the maximum tolerated dose of unshielded total body irradiation delivered from dual 60 Cobalt sources at an exposure rate of 8 cGy/min and given in fractions twice daily for total doses ranging from 12 Gy to 17 Gy. All patients received cyclophosphamide, 120 mg/kg administered over 2 days before total body irradiation. Allogeneic marrow was infused from HLA-identical siblings (n = 29) or one locus HLA incompatible family members (n = 3); three patients received cryopreserved autologous marrow and one patient received syngeneic marrow. The maximum tolerated dose of total body irradiation given as 2 Gy fractions twice a day was 16 Gy. One of eight patients receiving 12 Gy, none of four receiving 14 Gy, three of 20 receiving 16 Gy, and two of four receiving 17 Gy developed severe (Grade 3-4) regimen-related toxicity. The primary dose limiting toxicity was pneumonitis, followed by veno-occlusive disease of the liver, renal impairment, and mucositis. Five patients (14%) are alive, four disease-free 798-1522 days posttransplant. Twenty (56%) relapsed posttransplant. Further investigation of regimens containing 16 Gy of hyperfractionated total body irradiation is warranted to assess anti-tumor efficacy. PMID- 1639637 TI - Permanent interstitial implantation using palladium-103: the New York Medical College preliminary experience. AB - Palladium-103 is a low energy photon emitter available for permanent interstitial implantation. Pd-103 has energy and safety characteristics similar to Iodine-125, but its initial peripheral dose rate is approximately three times greater. This may provide improved control of rapidly proliferating tumors. At the Westchester Campus of New York Medical College, 15 patients with residual or recurrent unresectable lesions were implanted with Pd-103. There were five males and 10 females with an age range of 41 to 93 years (median 58). Implanted sites included the chest wall, nasopharynx, vagina, and zygomatic region. Peripheral doses ranged from 55 to 203 Gy (median 107 Gy). A complete response was achieved in eight patients and a partial response in seven patients, for an overall response rate of 100%. We noted improved control with smaller volumes and peripheral doses at or above 115 Gy. No unusual skin or mucosal reactions were recorded. Possible advantages of Pd-103 as a substitute for I-125 include improved control of rapidly proliferating tumors and a more rapid clinical response of lesions. Disadvantages include current higher cost and an impracticality in maintaining a running inventory because of the short half-life of the isotope. Our experience suggests that Pd-103 is an attractive alternative to I-125. PMID- 1639638 TI - Thymoma: treatment and prognosis. AB - Thirty-six patients with pathologically confirmed thymoma were treated at M.D. Anderson Cancer Center from 1962 to 1987. The tumors were staged based on invasion and intrathoracic dissemination. Twenty-one patients had total resection, five had subtotal resection, and 10 had biopsy alone. Twenty-two patients had definitive megavoltage radiation therapy with a median dose of 50 Gy. The 5-year, disease-free survival by stage was 74% for Stage I (n = 11), 71% for Stage II (n = 8), 50% for Stage III (n = 10), and 29% for Stage IVA (n = 7) (p less than 0.03). The 5-year, disease-free survival by extent of surgery was 74% for total resection, 60% for subtotal resection and 20% for biopsy only (p = 0.001). There were 15 patients with recurrences: two in Stage I, two in Stage II, five in Stage III, and six in Stage IVA. The median months to relapse, for those who failed treatment, were 46, 36, 2, and 13 for Stages I, II, III, and IVA respectively. Of the patients with recurrences four had a total resection, two subtotal resection, and nine biopsy only. Only one patient had distant metastases as the first site of relapse without intrathoracic relapse. For the eight patients who relapsed following radiation therapy, four were in the radiotherapy field. All four of the in-field failures were in patients who had a partial response. There were insufficient numbers of patients to determine a dose response to radiotherapy. For patients with invasive, incompletely resected disease, a multimodality approach may be necessary for long term, disease-free survival. PMID- 1639639 TI - Radiation therapy as a treatment for benign lymphoepithelial parotid cysts in patients infected with human immunodeficiency virus-1. AB - Patients who are infected with the human immunodeficiency virus (HIV) may develop benign lymphoepithelial cysts within the parotid gland that cause severe facial deformity. Standard treatment for this disorder has been superficial parotidectomy, repeated fine-needle aspirations or observation alone. These approaches are unsatisfactory because elective surgery in immunocompromised patients should be avoided, the cysts recur soon after aspiration, and observation alone for a treatable deforming facial process is unacceptable. Radiotherapy's proven effectiveness in treating other benign disorders of the parotid gland led us to evaluate its usefulness as a treatment for this disorder. Eight patients with parotid enlargement, who were seropositive for HIV, received 8-10 Gy to the parotids in 1 week. Five patients had complete response and three patients had partial response. All were very satisfied with the cosmetic result. Treatment-related toxicity was well tolerated and consisted of mild xerostomia and transient taste loss. In all cases, these side effects resolved within 1 month. Radiation therapy thus appears to be an effective and well-tolerated treatment for AIDS-related parotid enlargement. PMID- 1639640 TI - The influence of lung and bone dosimetry on the choice of radiation energy for total body irradiation. AB - The radiation absorbed dose to lung and bone is of importance for total body irradiation performed prior to bone marrow transplantation for hematologic malignancies. The measurement and calculation of radiation absorbed dose to low density materials such as lung has been discussed in several publications and most total body irradiation procedures account for the increased radiation dose to the lung. However, radiation absorbed dose to bone and soft tissues within bone is not calculated and is assumed to be the same as the dose to soft tissues. Because the bone is different in both density and atomic number from soft tissues, radiation dose calculations are more complex for bone than for lung. As the energy of the radiation beam changes, the dose to heterogeneous tissue varies. This variation of the radiation dose is investigated for radiation beams ranging in energy from 60Cobalt to x-ray beams produced at 18 MV. The radiation absorbed dose to soft tissues within bone is found to increase relative to the dose to soft tissue for higher megavoltage radiations, while at the same time there is a decrease in lung dose. Therefore, since for total body irradiation procedures the target tissues are the soft tissues within bone, a higher dose to those tissues would be an advantage. PMID- 1639641 TI - Rapid two-dimensional dose measurement in brachytherapy using plastic scintillator sheet: linearity, signal-to-noise ratio, and energy response characteristics. AB - Because of the large dose gradients encountered near brachytherapy sources, an efficient, accurate, low-atomic number areal detector, which can record dose at many points simultaneously, is highly desirable. We have developed a prototype of such a system using thin plates of plastic scintillator as detectors. A micro channel plate (MCP) image intensifier was used to amplify the optical scintillation images produced by radioactive 125I and 137Cs sources in water placed 0.5-5.7 cm distance from the detector. A charge-coupled device (CCD) digital camera was used to acquire 2-D light-intensity distributions from the image intensifier output window. For both isotopes, a small area (2 x 3 mm2) PVT detector yields a CCD net count rate that is linear with respect to absorbed dose rate within +/- 3% out to 5.7 cm distance. Acquisition times range from 1.5-400 sec with a reproducibility of 0.5-5.5%. If a large-area (6 x 20 cm2) PVT detector is used, a four-fold increase in count rate and large deviations from linearity are observed, indicating that neighboring pixels contribute light to the signal through diffusion and scattering in PVT and water. A detailed noise analysis demonstrates that the image intensifier reduces acquisition time 10000-fold, reduces noise relative to signal 200-fold, and reduces amplifier gain noise as well. PMID- 1639642 TI - The structure for a radiation oncology protocol. The Committee of Radiation Oncology Group Chairmen. AB - Multi-institutional Cooperative Group clinical trials involving radiotherapy require unambiguous therapeutic guidelines, so that patients entered from each of the participating institutions will receive essentially uniform treatment. The technical guidelines for a Radiation Oncology Protocol presented in this report represents a consensus of the Radiotherapy Committees in the major NCI funded Cooperative Groups and is derived from over a decade of experience. Although they have been written for external beam therapy, they are applicable to brachytherapy with appropriate technical considerations. It is anticipated that further evolution will occur with the introduction of new technologies such as 3-D treatment planning and delivery, multi-leaf collimation and small field irradiation. PMID- 1639643 TI - Local control for locally advanced breast cancer: many opinions, few facts. PMID- 1639644 TI - Is more therapy better? Locoregional irradiation as part of aggressive therapy for poor risk breast cancer patients. PMID- 1639645 TI - The pathogenesis of radiation myelopathy: widening the circle. PMID- 1639646 TI - Comparison of "orthovoltage" X-ray versus "megavoltage" electrons in treating tumors near the eye. PMID- 1639647 TI - The outcome of definitive radiotherapy for localized prostate carcinoma. PMID- 1639648 TI - Radical prostatectomy--possible indications for postoperative radiotherapy. PMID- 1639649 TI - Late effects after radiotherapy in head and neck malignancies: overall treatment time, number of fractions and the linear-quadratic model. PMID- 1639650 TI - Does hyperfractionation reduce late complications in head and neck cancers? PMID- 1639651 TI - Proposed universal standard for specifying schedules. PMID- 1639652 TI - ASTRO Gold Medal address. PMID- 1639653 TI - Long-term radiation complications following conservative surgery (CS) and radiation therapy (RT) in patients with early stage breast cancer. AB - The frequency of brachial plexopathy, rib fracture, tissue necrosis, pericarditis, and second non-breast malignancies occurring in the treatment field among 1624 patients with early stage breast cancer treated with conservative surgery and radiation therapy at the Joint Center for Radiation Therapy between 1968 and 1985 is reported. The median follow-up time for survivors was 79 months (range 5-233 months). Brachial plexopathy was related to the use of a third field, the use of chemotherapy and the total dose to the axilla. Brachial plexopathy developed in 20 of 1117 women (1.8%) who received supraclavicular irradiation with or without axillary irradiation. The median time to its occurrence was 10.5 months (range 1.5-77 mo), and the majority (80%) of cases completely resolved. Among patients treated with a three-field technique, the incidence of brachial plexopathy was 1.3% (13/991) in patients treated with a dose to the axilla of less than or equal to 50 Gy, compared with 5.6% (7/126) in women treated with an axillary dose of greater than 50 Gy. The incidence of brachial plexopathy was 4.5% (15/330) among patients receiving chemotherapy, compared with 0.6% (5/787) when chemotherapy was not used (p less than 0.0001). Rib fracture was seen in 29 patients (1.8%), at a median time of 12 months following treatment (range 1-57). In all cases, the rib fracture healed without intervention. The incidence of rib fracture was 2.2% (28/1300) among patients treated on a 4 MV linear accelerator, compared with 0.4% (1/276) for patients treated on a 6 or 8 MV machine (p = 0.05). Of patients treated on a 4 MV machine, 0.4% (1/279) developed a rib fracture when a whole breast dose of 45 Gy or less was given, 1.4% (10/725) after receiving between 45 and 50 Gy, and 5.7% (17/296) following 50 Gy or higher. Tissue necrosis requiring surgical correction developed in three patients (0.18%) 22, 25, and 114 months after treatment. Presumed pericarditis (requiring hospitalization) was seen in 0.4% of women (3/831) who received radiation therapy to the left breast 2, 2, and 11 months after the start of treatment. Three women (0.18%) developed sarcomas in the treatments field at 72, 107, and 110 months, for a 10-year actuarial rate of 0.8%. Two of these sarcomas developed in areas of probable match-line overlap. One patient (0.06%) developed an in-field basal cell carcinoma at 42 months. In conclusion, the risk of significant complications following conservative surgery and radiation therapy for early stage breast cancer is low.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1639654 TI - Are cosmetic results following conservative surgery and radiation therapy for early breast cancer dependent on technique? AB - To assess the cosmetic results in relation to treatment technique, we retrospectively reviewed the results for 1159 Stage I-II breast cancer patients treated with conservative surgery and radiotherapy between 1970-1985. All patients underwent gross excision followed by radiation therapy including an implant or electron beam boost. The total dose to the primary site was greater than or equal to 60 Gy. Because of technical modifications introduced over time after 1981, the population was divided arbitrarily into two cohorts: 504 patients treated through 1981 and 655 treated between 1982-1985. Median follow-up time for surviving patients in the two cohorts were 107 months and 67 months, respectively. Cosmetic outcome was evaluated by the examining physician and scored as excellent, good, fair or poor. Excellent results at 5 years were scored in 59% of early cohort patients and 74% of the latter cohort (p = 0.002). Acceptable results (either good or excellent) were seen in 84% and 94%, respectively (p = 0.02). In the latter cohort, the likelihood of achieving an excellent result, but not an acceptable result, was significantly related to the volume of resected breast tissue and the use of chemotherapy. The number of fields (three-field technique, provided that fields are precisely matched, compared to tangents only) and boost type (implant vs electrons) did not influence the cosmetic outcome. We conclude that our current technique using breast RT to 45-46 Gy and a boost to the primary site of 16-18 Gy is associated with a high likelihood of acceptable cosmetic results and that this likelihood is not diminished by the use of adjuvant chemotherapy, a large breast resection, the use of a third field, or boost type. PMID- 1639655 TI - The effect of systemic therapy on local-regional control in locally advanced breast cancer. AB - One hundred and seven patients with locally advanced breast cancer were prospectively referred for multimodality treatment on protocol using chemohormonal therapy to maximal response followed by local treatment and maintenance therapy. Forty-eight patients (45%) were diagnosed with Stage IIIA disease, 46 (43%) with Stage IIIB inflammatory cancer, and 13 (12%) with Stage IIIB non-inflammatory disease. Induction therapy consisted of cyclophosphamide, doxorubicin, methotrexate, and 5-fluorouracil with hormonal synchronization using tamoxifen and conjugated estrogens. Local treatment was determined by response to chemotherapy. Patients with a clinical parital response underwent mastectomy followed by local-regional radiotherapy while patients with a clinical complete response were biopsied for pathologic correlation. Those with residual disease received mastectomy followed by radiotherapy while those with a pathologic complete response received radiation only to the intact breast and regional nodes. With a median follow-up of 64 months, patients with IIIA disease had a significantly lower local-regional failure rate compared to IIIB inflammatory patients, with the 5-year actuarial local-regional failure rate as only site of first failure 3% for IIIA disease versus 21% for IIIB inflammatory cancer (p = .02), and local-regional failure as any component of first failure 12% versus 36% (p = .01), respectively. When local-regional failure was analyzed by repeat biopsy, 5/31 (16%) patients with a pathologic complete response treated with radiation only developed a local-regional failure versus 2/53 (4%) with residual disease treated with mastectomy and postoperative radiotherapy. The 5-year actuarial local-regional failure rate as first site of failure was 23% for radiation only versus 5% for mastectomy and post-operative radiotherapy (p = .07). The response to chemotherapy did not reliably predict local-regional control. Both relapse-free survival and overall survival were significantly better for IIIA versus IIIB patients; stratification by repeat biopsy did not however, significantly affect either relapse-free or overall survival. PMID- 1639656 TI - Radiosensitization of cultured human colon adenocarcinoma cells by 5 fluorouracil: effects on cell survival, DNA repair, and cell recovery. AB - Although 5-fluorouracil (5-FU) is commonly used in conjunction with radiotherapy to treat gastrointestinal malignancies, the molecular mechanisms underlying the clinically observed therapeutic advantage of this combination of agents have not been clearly established. The present in vitro studies addressed the possibility that the radiosensitization of log-phase cultured human colon adenocarcinoma cells by postirradiation administration of 5-FU was accompanied by an interference either with the rejoining of radiation-induced DNA double-strand breaks (DSB's) or with recovery from potentially lethal damage (PLD). Significantly more killing was observed in cells exposed to gamma-rays (1-6 Gy) and then treated with 5-FU (100 micrograms/mL; 0.77 mM) for 1 hr at 37 degrees C than in cells given gamma-rays but not 5-FU; essentially, the survival curve shoulder was removed. DSB rejoining measured using the neutral filter elution method after exposure to 25 Gy was identical regardless of whether 5-FU (100 micrograms/mL) was present during the repair period; thus, radiosensitization by this high-concentration postirradiation 5-FU protocol does not appear to be a result of interference with the overall rate of ligation of gamma-ray-induced DSB's. The effect of 5-FU on the ability of log-phase cells to recover from that sector of PLD that can be expressed by postirradiation incubation with hypertonic (0.5 M) salt solution (HSS) was also examined. When irradiated cells were treated with 5-FU during their recovery period and then incubated with HSS, no clonogenic cells survived. Therefore, although it was not possible to assess the actual kinetics of recovery from gamma-ray-induced PLD in 5-FU-treated cells, the drug clearly altered the metabolism or structure of the cells such that their susceptibility to HSS was markedly enhanced. PMID- 1639657 TI - Restriction enzyme-induced DNA double-strand breaks as a model system for cellular responses to DNA damage. AB - To learn more about cellular responses to DNA double-strand breakage, we used three methods to assay cellular damage after treatment with a restriction enzyme that causes DNA double-strand breaks by cleaving at specific recognition sites in the DNA. Chinese hamster ovary cells were treated with increasing doses of Pvu II and studied for double-strand breakage, chromosomal aberration yield, and cell survival. The yield of DNA double-strand breaks, as measured by pulsed-field gel electrophoresis, increased at concentrations up to 500 units and saturated thereafter. The maximum yield of metaphase cells showing aberrant chromosomes was reached at 100 units and stayed constant up to 1,000 units. Although exchange type aberrations saturated at approximately 4.5 per cell at 100 units, deletion type aberrations appeared to increase at concentrations up to 500 units. Cell survival, as measured by colony-forming ability after Pvu II treatment, saturated at 100 units. The observed dose-response data are probably due to the saturation of accessible Pvu II cleavage sites within the cell. These data indicate that restriction enzymes induce the same DNA-damaging effects as many of the agents used in cancer treatment. Because the primary DNA lesion induced by restriction enzymes is known, they provide a unique opportunity to understand cellular responses to DNA damage and repair. PMID- 1639658 TI - Incest, Freud's seduction theory, and borderline personality. AB - In the early 1890s Freud expressed the belief that many cases of hysteria had a basis in childhood incest. Later he expressed a different view, emphasizing childhood fantasies of sexual intimacies with a parent that never actually took place. Freud never totally repudiated his original seduction theory, however, maintaining to the end of his life that at least some cases of actual incest occurred and that these instances underlay certain types of psychopathology. In our era we have become aware that incest is frequently a forerunner of subsequent borderline disorders, especially in women hospitalized with borderline personality disorder (B.P.D.). All the clinical manifestations of B.P.D. can be related to the prior incest experiences. PMID- 1639659 TI - Stress in the personal and professional development of a psychoanalyst. PMID- 1639660 TI - Reflections on dream material from Arctic Native people. AB - This article presents several theoretical and methodological perspectives from which psychoanalytic understanding of the dreams of people in a foreign culture might be obtained. The dreams of two Inuit (Eskimos) are examined as they reflect the cosmologies, narrative styles, and individual psychologies of each dreamer. Caveats are noted regarding notions of universal symbolism, typical cultural character, and facile interpretations of dreams. PMID- 1639661 TI - The parenting process: a psychoanalytic perspective. PMID- 1639663 TI - Fromm's concept of biophilia. PMID- 1639662 TI - The semiotics of gender. AB - The semiotics of gender are investigated in this article for the purpose of exploring the way that deep unconscious motives in relationship to cultural biases give rise to gender concepts. Theories of semiotic processes, including Jacques Lacan's concept of the psychoanalytic signifier, are explained briefly and applied to the signs of gender. The article concludes that gender concepts develop out of biology, unconscious feelings, and social patterning, and are not given, natural, and irrevocable. PMID- 1639664 TI - The adolescent crack dealer: a failure in the development of empathy. PMID- 1639665 TI - Psychoanalysis and psychosomatics: a new synthesis. AB - The usefulness of psychoanalysis to psychosomatic medicine has been limited by the longstanding assumption that the psychological disorder in psychosomatic patients resembles the conflict-based psychopathology that Freud identified in psychoneurotic patients. Recent investigations of the alexithymia construct, and the discovery that social relationships can influence health over the entire life span, have challenged this assumption and created an opportunity for a new and active involvement of psychoanalysis with psychosomatic medicine. In this contribution, I offer a synthesis of contemporary psychoanalytic observations and theories with concepts and research findings from developmental psychology, developmental biology, and the biomedical sciences. The proposed synthesis is consistent with the view that living organisms are self-regulating cybernetic systems; it also extends an evolving new psychosomatic model that conceptualizes illnesses and diseases as disorders of psychobiological regulation. A modern psychoanalytic approach to physically ill and disease-prone individuals focuses less on the resolution of neurotic conflicts, and more on correcting deficits in these patients' self and object representations and capacity cognitively to process emotions. PMID- 1639666 TI - The phoenix rises from eros, not ashes: creative collaboration in the lives of five impressionist and postimpressionist women artists. AB - Women yearn to express themselves through their affiliative bonds and professional goals. Historically, it has been difficult for women to find and maintain close affirmative ties with men while they also strived to advance their careers. The lives of five impressionist and postimpressionist women artists in fin-de-siecle Europe permit a glimpse into the possibilities and pitfalls of relationships in career development. When mentors or supportive partners are available to women, their creative productivity flourishes. In contrast, when the male partner seeks greedily to control or enviously to attack the woman's aspirations, her creativity wanes, and her life may be ravaged. Yet the keystone of any creative partnership is the ability to reckon with the potential sources of destructiveness within one's self that may lead to disparagement of the other. The lives of men and women may be enhanced when neither partner disavows or seeks to denigrate the talents of the other. Creative partnerships that support the emotional and productive intensity of both members of the dyad can lead to great personal expansion and enrichment for the culture at large. PMID- 1639667 TI - ERP augmenting/reducing and sensation seeking: a critical review. AB - Event-related potentials (ERPs) are generally considered capable of throwing light on the biological basis of personality traits. In particular, the ERP augmenting/reducing (A/R) phenomenon has been consistently associated with personality dimensions such as sensation seeking or impulsivity. However, doubts have been expressed regarding the validity of published evidence that individuals scoring high as sensation seekers are ERP augmenters. Reports of A/R-sensation seeking correlation in the opposite direction (in keeping with Petrie's hypotheses) threaten the construct validity of A/R, and lack of intermodal consistency throws serious doubts upon the existence of the central input regulating mechanism once thought to be associated with sensation seeking. With the aim of clarification this article reviews the literature on the relationship between ERP A/R and sensation seeking, discusses the chief problems confronted by research in this area, and makes suggestions for future studies. It is concluded that experimental conditions of stimulus intensity and inter-stimulus interval may have played a part in the inconsistencies. The need to use a variety of measures of sensation seeking is stressed, and a number of other recommendations for research in this field are made. PMID- 1639668 TI - Event-related potentials in the dual task paradigm: P300 discriminates engaging and non-engaging films when film-viewing is the primary task. AB - Five groups of subjects (11-16/group) were run in three experiments. In each study P300 amplitude and latency were studied as a function of three sensory task conditions: (1) baseline (oddball task: target and non-target tones only); (2) boring film viewing plus oddball task; and (3) exciting film viewing plus oddball task. In Experiment I, target probability was P = 0.22. In Experiments II and III, each of two groups of subjects was run at P = 0.22 or P = 0.33. Two different exciting films and two different boring films were used. Oddball-target amplitude was found to consistently decrease from baseline to boring to exciting film-viewing conditions at P = 0.22. At P = 0.33, the 2-film discrimination was successful in one of two experiments. P300 amplitude consistently differed from baseline to film-viewing conditions. For the non-target (frequent) tones, the smaller P300 amplitudes consistently discriminated boring and exciting films, as well as single from dual tasks. For target P300 latency, single (baseline) and dual (film-watching) conditions were always discriminable, but boring and exciting films were not discriminable. There were no effects on non-target P300 latency. N100 amplitude discriminated baseline and film viewing conditions, but not boring and engaging films. PMID- 1639669 TI - Visual attention and evoked otoacoustic emissions: a slight but real effect. AB - The effect of auditory or visual attention tasks on the peripheral auditory system, studied by Brainstem Auditory Evoked Potentials (BAEPs), electrocochleography or Evoked Oto-Acoustic Emissions (EOAEs), has been a subject of controversy. To investigate the divergences in findings, a study using EOAE and visual and auditory attention was run on 12 subjects. A significant effect during visual attention was obtained. A general diminution of EOAEs of 0.35 dB (equivalent reduction) was found. This result seems to prove that BAEPs are not the best technique to reveal the effect of attention on cochlear mechanisms, because of the weakness of the effect. PMID- 1639670 TI - P3 from auditory stimuli in healthy elderly subjects: hearing threshold and tone stimulus frequency. AB - The P3 event-related potential (ERP) was elicited by auditory stimuli under two conditions: (1) 250 Hz standard, 500 Hz target; and, (2) 1000 Hz standard, 2000 Hz target. A group with normal hearing (n = 10), defined as subjects with less than a 16 dB loss at each tone frequency was compared to a group with hearing impairment (n = 8), defined as subjects with a loss of 16 dB or more at each tone frequency. The hearing impaired group showed significant P3 latency prolongations compared to those with normal hearing under the 2000 Hz, but not the 500 Hz target, even though subject age was used as a covariate. Under both conditions, hearing impaired subjects showed reduced P3 amplitudes compared to those with normal hearing. These findings are discussed in relation to the sensitivity of ERP assessment procedures in older adults. PMID- 1639671 TI - Psychophysiological treatment for learning disabilities: controlled research and evidence. AB - Research data are presented on the effects of a psychophysiological treatment method for learning disabilities. A total of 238 subjects with learning disabilities were selected based on their school records. Of these, 105 received the full treatment which consisted of the manipulation and maintenance of bilateral electrodermal activity between 6.5-8.5 mu mhos simultaneously combined with increasingly complex perceptual tasks (Mangina, 1981a, b, c; Mangina and Beuzeron-Mangina, 1988). Another 133 subjects with learning disabilities were assigned into four different conditions: (a) classmate controls; (b) only attachment of electrodes; (c) only optimal activation; (d) only perceptual stimulation. Evidence for the effectiveness of the treatment method was found based on different experimental conditions which are presented in this paper. ANOVA and multiple comparison tests indicate that beneficial effects were only obtained by the administration of the full treatment method and were significant at all three time intervals investigated (P less than 0.001). The evidence supports that the treatment method has induced a 'synergistic simultaneity' which is required by the brain both in terms of its bilaterally 'optimal' physiological activation and the appropriate quality of incoming stimulation in order to produce a beneficial neural integration. PMID- 1639672 TI - The facilitative effect of facial expression on the self-generation of emotion. AB - Twenty-seven female undergraduates completed three tasks: (1) feel four emotions (happiness, sadness, anger, peacefulness); (2) express these emotions, without trying to feel them; and (3) feel and express clearly these four emotions. During each trial subjects pressed a button to indicate when they had reached the required state, and the latency from emotion cue to button press was measured. Heart rate, skin conductance and EMG from four facial sites (brow, cheek, jaw and mouth) were recorded for 15 s before and after the button press and during a baseline period prior to each trial. Self-reports were obtained after each trial. Facial EMG and patterns of autonomic arousal differentiated among the four emotions within each task. Shorter self-generation latency in the Feel-and-Show versus the Feel condition indicated the facilitative effect of facial expression on the self-generation of emotion. Furthermore, the presence of autonomic changes and self-reported affect in the Show condition supports the sufficiency version of the facial feedback hypothesis. The self-generation method employed as an emotion elicitor was shown to reliably induce emotional reactions and is proposed as a useful technique for the elicitation of various emotional states in the laboratory. PMID- 1639673 TI - Physiological and subjective effects of traffic noise: the role of negative self statements. AB - This study assesses physiological and subjective effects of traffic noise and the mediator role that negative self-statements play. 84 female students underwent a Physiological Reaction Test to two 15 min presentations of high intensity traffic noise (85-95 dB) under two Noise conditions--with and without negative self statements. Half of the subjects were given specific instructions to increase the credibility of the self-statements. Dependent variables were frontal EMG, electrodermal variables (conductance level and number of responses) and subjective tension. Traffic noise provoked subjective tension and physiological responses. Only the number of electrodermal responses habituated between noise presentations, the rest of the physiological variables did not habituate. Negative self-statements had the greatest effect on frontal EMG. In fact, only the noise with negative self-statements condition produced a significant EMG increase in the first part of the Test. Instructions increased subjective tension and also increased the effect of the self-statements on the electrodermal variables. The implications of these results for psychosomatic problems and the importance of negative self-statements are discussed. PMID- 1639674 TI - Fast decrement with stimulus repetition in ERPs generated by neuronal systems involving somatosensory SI and SII cortices: electric and magnetic evoked response recordings in humans. AB - The effect of stimulus repetition (short trains of stimuli with 1-s inter stimulus intervals and 15-s inter-train intervals) on both electric and magnetic evoked responses were studied in four subjects. In addition to the later N140 and P300 deflections in electric potentials, a distinct and immediate amplitude decrement was obtained also for the earlier P50 and P100 deflections. The magnetic evoked responses also demonstrated the amplitude decrement for 50 ms (M50) and 100 ms (M100) latency deflections. The time-course and degree of amplitude decrement of the M100 magnetic response corresponded especially well to those of P100 electric deflections. The results thus show the rate effect on electric and magnetic responses at 50 and 100 ms latencies, and further suggest that the electric and magnetic responses, reflecting the activation of somatosensory SI and SII cortical areas at these latencies, respectively, are generated by related neuronal mechanisms. PMID- 1639675 TI - Oddball-evoked P300-based method of deception detection in the laboratory. II: Utilization of non-selective activation of relevant knowledge. AB - We used a deception paradigm modeled on the type used for pre-employment screening procedures. Our novel dependent measure was P300 amplitude. Event related potentials (ERPs) were recorded while subjects were presented with a list of eight antisocial acts one at a time, and one target-response phrase to which a 'yes' button press was required. Subjects were instructed to try to escape detection during the ERP test if they were guilty of any of the acts. After the ERP test, ground truth was established by the completion of an innocent/guilty check list of antisocial acts under perceived anonymous conditions tending to favor honest responding. Subjects were classified as innocent (n = 14) or guilty (n = 17) based on their check list response to the relevant act 'Used Falsified ID'. When comparing the P300 amplitudes in response to the relevant and to another act, we found that most group analyses revealed significant differences between guilty and innocent subjects. The subjects were also individually classified by a 3-step algorithm which involved: (1) a bootstrap amplitude test that compared the bootstrapped amplitudes of the P300s to the relevant and to another act; (2) relevant-to-target item P300 amplitude ratios; and (3) relevant act P300 amplitudes. Overall, the algorithm yielded 87% accuracy. The present study was intended to be an advance over our previous study (Rosenfeld, et al., 1991), in which we correctly classified 89% of the subjects using a similar P300 based deception detection paradigm. However, the possible confounding limitation of that study was that subjects had to complete an innocent/guilty check list of their antisocial acts prior to the ERP test. The present study investigated the accuracy of the P300-based test when subjects did not admit or selectively rehearse their guilt of the relevant act prior to the ERP test. PMID- 1639676 TI - Avocado poisoning. PMID- 1639678 TI - AVMA initiative begins Capitol Hill climb. PMID- 1639677 TI - Relief for relief veterinarians. PMID- 1639679 TI - From the bottom(s) up: how two veterinarians escaped their world of drugs and alcohol. PMID- 1639680 TI - Amend FD&C Act, says Veterinary Medicine Advisory Committee. PMID- 1639681 TI - What's holding up animal drug approval? PMID- 1639682 TI - Follow-up study of owner attitudes toward home care of paraplegic dogs. AB - A questionnaire was mailed to 30 owners of paraplegic dogs who had been caring for their dogs at home for 3 to 72 months. It was designed to collect information on demographic variables, duration of ownership and paralysis, age of the pet, pet/owner relationship, owner expectations and perceptions of the pet's quality of life, problems the pet experienced, effect that maintaining a paralyzed pet had on the owners' quality of life, and whether use of a cart was beneficial. Significant correlation was found between prior expectations that the pet would lead a high-quality life and perception that the pet, in fact, had a high quality of life during paralysis (r2 = 0.61, P = 0.01). Owners who had anticipated that extra work would be necessary to care for their paraplegic dog had a more positive attitude toward home care (r2 = 0.55, P = 0.03). Overall, owners involved in the study were satisfied with all aspects of maintaining paraplegic dogs at home. Our findings support the feasibility of dedicated owners successfully maintaining small (average body weight, 9 kg) paraplegic dogs at home for extended periods. PMID- 1639683 TI - Economic impact of an epizootic of pseudorabies in a commercial swine herd in Ohio, achieving test negative status and quarantine release by use of vaccination and test and removal. AB - The effect of pseudorabies in a commercial farrow-to-finish operation on selected production and economic values was estimated. Pseudorabies was first diagnosed in this herd by circle testing done in March 1988, as a required part of follow up from another herd that had been diagnosed with pseudorabies in the area. A pseudorabies virus vaccination program was initiated in the herd at that time. The mean litter size of pigs born alive varied from 9.26 to 10.02 pigs/litter throughout the study period; however, there was a twofold increase in suckling pig mortality and a 2.6-fold increase in nursery pig mortality when the months of the epizootic were compared with pre-epizootic months. In the 6-month period following the epizootic, suckling pig mortality was three-fold higher than that reported in the preepizootic months. Total net loss for this operation was estimated at $99,700 from when the epizootic started until eradication, when calculating losses directly. The major economic losses (76.5% of total loss) were related to suckling pig mortality, which was $16,240 during the epizootic or $24/inventoried sow/week; $19,395 in the 6 months following the epizootic or $3.8/inventoried sow/week; and $40,628 thereafter until eradication 26 months later or $0.37/inventoried sow/week. Nursery pig mortality losses were 12.6% of total net losses; $754 during the epizootic, $357 in the 6 months after the enzootic, and $11,444 thereafter until eradication 26 months later. Sow culling and deaths accounted for 9.4% of net losses that took place from 6 months after the epizootic until eradication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639684 TI - To live or not to live with the risk of extra-label use. PMID- 1639685 TI - Use of ultralente insulin in cats with diabetes mellitus. PMID- 1639686 TI - Building good client relations. PMID- 1639687 TI - Circulatory shock and cardiopulmonary resuscitation: current perspectives and future directions. PMID- 1639688 TI - New perspectives in circulatory shock: pathophysiologic mediators of the mammalian response to endotoxemia and sepsis. PMID- 1639690 TI - Role of oxygen-derived free radicals in the pathogenesis of shock and trauma, with focus on central nervous system injuries. PMID- 1639689 TI - Involvement of prostaglandins and leukotrienes in the pathogenesis of endotoxemia and sepsis. PMID- 1639691 TI - Clinical aspects of septic shock and comprehensive approaches to treatment in dogs and cats. PMID- 1639692 TI - Systemic and pulmonary reactions in swine with endotoxemia and gram-negative bacteremia. PMID- 1639693 TI - Endotoxemia and gram-negative bacteremia in swine: chemical mediators and therapeutic considerations. PMID- 1639694 TI - Shock attributable to bacteremia and endotoxemia in cattle: clinical and experimental findings. PMID- 1639695 TI - Endotoxemia and septicemia in horses: experimental and clinical correlates. PMID- 1639696 TI - Management of septic shock. PMID- 1639697 TI - Basic life support and external cardiac compression in dogs and cats. PMID- 1639698 TI - Recognition and frequency of dysrhythmias during cardiopulmonary arrest. PMID- 1639699 TI - Controversial issues in drug treatment during cardiopulmonary resuscitation. AB - The goal of advanced life support in CPR must be to restore and maintain respiratory and hemodynamic effectiveness, and to correct the underlying dysrhythmia. Optimal basic life-support techniques must be continued to meet these goals. Many drugs have been suggested in the treatment of cardiac arrest, but unfortunately, drug effects are inconsistent and resuscitation rates remain low. Epinephrine, atropine, lidocaine, bretylium, and naloxone remain important drugs for consideration in CPR in most animals with cardiac arrest. The best chance of survival remains in early recognition of animals susceptible to arrest and in treatment of the underlying cause. PMID- 1639700 TI - Internal cardiac compression. PMID- 1639701 TI - Effects of lasalocid on coccidial infection and growth in young dairy calves. AB - Effects of lasalocid on coccidial infection and on calf growth were examined in 16 Holstein bull calves. Calves were assigned randomly to a 2 x 2 factorial arrangement of starter ration containing 0 or 40 mg of lasalocid/kg of starter, beginning when calves were 3 days old (SE = 0.046), and single oral inoculation with 0 or 30,000 sporulated oocysts (Eimeria bovis) at 28 days. Pelleted calf starter was fed ad libitum from day 1; milk replacer was fed at a rate of 3.6 kg/d until day 28. Mean daily gain, dry-matter intake, and body weight were increased in calves fed lasalocid and decreased in those inoculated with coccidia. Addition of lasalocid to the feed improved gains by 8% in uninoculated calves and by 50% in inoculated calves. Fecal oocyst numbers were reduced when lasalocid was fed to inoculated calves. Feces were more abnormal in calves inoculated with coccidia. Respiration rates, rectal temperatures, PCV, and serum sodium and potassium concentrations were unaffected by treatment. On the basis of findings in this study, lasalocid minimized effects of coccidial challenge inoculation and increased growth of calves. PMID- 1639702 TI - Cardiopulmonary and behavioral effects of combinations of acepromazine/butorphanol and acepromazine/oxymorphone in dogs. AB - Cardiopulmonary and behavioral effects of the following tranquilizer-opioid drug combinations were compared in conscious dogs: acepromazine (0.22 mg/kg of body weight, IV) and butorphanol (0.22 mg/kg, IV); acepromazine (0.22 mg/kg, IM) and butorphanol (0.22 mg/kg, IM); and acepromazine (0.22 mg/kg, IV) and oxymorphone (0.22 mg/kg, IV). Marked sedation and lateral recumbency that required minimal or no restraint was achieved with every drug combination. Analgesia was significantly better in dogs receiving oxymorphone than in dogs receiving butorphanol, as evaluated by response to toe pinch. There were no significant differences between the effects of the 3 drug combinations on heart rate, respiratory rate, arterial blood pressure, body temperature, and arterial pH, PCO2, PO2, and bicarbonate concentration. Heart rate, respiratory rate, and systolic arterial pressure decreased significantly over time with all drug combinations. Total recovery time (minutes from the initial injection to standing) was significantly longer in the dogs given acepromazine and oxymorphone. PMID- 1639703 TI - Salivary mucocele associated with dirofilariasis in a dog. AB - Salivary mucocele associated with dirofilariasis was diagnosed in a dog with a mass in the cranioventral cervical region. The diagnosis was based on the finding of microfilariae in fluid aspirated from the mucocele, immunoassay confirmation of circulating Dirofilaria immitis antigen, and the finding of an adult filariid within the mucocele. Drainage of the mucocele and treatment of the D immitis infection resulted in resolution of the mucocele and dirofilariasis. PMID- 1639704 TI - Keratoconjunctivitis sicca and diabetes mellitus in a dog. AB - Diabetes mellitus and keratoconjunctivitis sicca were diagnosed in a female Poodle. The dog was treated for diabetes and keratoconjunctivitis sicca until blood glucose concentrations were within normal limits. Treatment for keratoconjunctivitis sicca was suspended then, and signs of this disorder did not appear again. Most of the factors known to predispose to keratoconjunctivitis sicca were not applicable to this dog. On the basis of observations made in this dog, we suggest that diabetes mellitus and keratoconjunctivitis sicca may be linked. Clinical signs of the disorders developed simultaneously and resolved when diabetes mellitus was controlled with insulin. PMID- 1639705 TI - Insect defensive spray-induced keratitis in a dog. AB - Ulcerative keratitis was seen in a dog after it had been sprayed in the face by the larger striped walking stick, Anisomorpha buprestoides. This insect has defensive glands from which it can spray a secretion that is lachrymogenic and irritating. PMID- 1639706 TI - Hypervitaminosis A in a cat. AB - A 10-year-old cat that was kept on a diet consisting largely of raw liver was evaluated because of lethargy, partial anorexia, and weight loss of several months' duration. The cat's head and neck were rigidly extended, and a hard mass was palpable in the ventral cervical region. Cervical and thoracic radiography revealed proliferative bony lesions of the cervical and thoracic vertebrae as well as of the sternum and costal cartilages. Serum vitamin A concentration was 4 times normal. For reasons unrelated to hypervitaminosis A, euthanasia and necropsy were performed 6 months after evaluation. The skull and the cervical and first few thoracic vertebrae were rigidly fused, and the vertebral architecture was altered by deposition of new bone. The sternum and costal cartilages were similarly affected. The historical, physical, radiographic, laboratory, and postmortem findings were consistent with the diagnosis of hypervitaminosis A. On the basis of findings in this cat, hypervitaminosis A should be suspected in any sick cat fed a diet consisting partly or completely of raw liver. PMID- 1639708 TI - Nonpharmacologic management of stereotypic self-mutilative behavior in a stallion. AB - Self-mutilative behavior, a form of stereotypic behavior, can be a serious problem in stallion management. An 11-year-old Quarter Horse stallion was referred for evaluation of repeated episodes of self-mutilation and aggressive behavior. Historically, this behavior worsened when the horse was isolated from other animals and confined to a stall for long periods. Observations of the stallion revealed episodes of self-mutilation and other forms of stereotypic behavior precipitated by stressful situations. Modification of this behavior was achieved by environmental and nutritional management and provision of adequate exercise. Nonpharmacologic intervention can be a simple and inexpensive way to correct self-mutilative behavior. PMID- 1639709 TI - Ileocecal intussusception corrected by resection within the cecum in two horses. AB - Irreducible ileocecal intussusceptions pose a difficult surgical problem. Strangulating ileocecal intussusceptions involving the ileum and jejunum were identified in 2 horses undergoing exploratory laparotomy because of colic. Surgical correction in both horses was achieved by amputation of the ileocecal intussusception from within the cecal lumen, via typhlotomy. The inverted ileal stump was blindly stapled near the ileocecal orifice after pulling the intussusceptum into the cecum. A jejunocecostomy was performed to reestablish intestinal continuity. PMID- 1639707 TI - Ultrasonographic imaging of a keratoma in a horse. AB - Ultrasonography was used to confirm the tentative diagnosis of keratoma in a horse admitted for chronic progressive lameness. A definitive diagnosis of keratoma traditionally has been diagnosed by history, clinical findings, and radiographic evaluation. Confirmation of the keratoma by use of ultrasonography facilitated the formulation of a treatment plan that resolved the condition. PMID- 1639710 TI - Cystic structures in the guttural pouch (auditory tube diverticulum) of two horses. AB - Two horses were examined for compression of the pharynx from the dorsal pharyngeal wall. Neither horse had a patent opening of 1 of the guttural pouches. Radiography of the guttural pouch region revealed a retropharyngeal opacity that occluded 1 guttural pouch. Organisms were not isolated on bacteriologic culture of fluid obtained from the affected guttural pouch. Surgical exploration of the guttural pouch revealed the lining to be easily removeable by blunt dissection in 1 horse; however, the lining was more firmly attached and removal was not attempted in the second horse. A fenestration between the normal and affected guttural pouch was created in both horses to allow for drainage. The etiopathogenesis of the cyst in the guttural pouches is unknown. PMID- 1639711 TI - Distal metacarpal sequestration in a bison. AB - A 2-year-old 400-kg female American bison was admitted for evaluation and treatment of an open fracture of the right metacarpal bones 3 and 4. Radiography revealed osteolysis of the distal metaphysis and epiphysis, with extensive bony callus formation along the dorsoproximal and proximomedial aspects extending distally to the proximomedial aspect of the proximal phalanx. Evidence of periosteal or bony proliferation at the fracture site or along the distal segment of the third and fourth metacarpal bones was not visible, suggesting that the distal fracture fragment was becoming a sequestrum. Treatment consisted of soft tissue debridement and placement of the limb in a full-limb cast. The cast was changed every 4 weeks until the sequestrum was removed and the bone healed. It is rare for the distal half of a long bone to sequester following fracture. Additionally, it is remarkable that the sequestrum served as a buttress, which prevented collapse of the bone until the sequestrum was replaced by functional bony callus. PMID- 1639712 TI - Ocular lymphangiosarcoma in a cow. AB - Ocular lymphangiosarcoma was diagnosed in a Holstein cow with a progressively enlarging limbal mass. The cow was treated by exenteration. The cow survived for 2 years without clinical signs of recurrence. Lymphangiosarcoma is a vascular neoplasm that rarely has been reported in domestic animals. In other species, it has a high rate of metastasis and is associated with poor long-term survival. PMID- 1639713 TI - Respiratory and cardiopulmonary arrest in dogs and cats: 265 cases (1986-1991). AB - Outcomes of cardiopulmonary arrest and resuscitation in clinically affected dogs and cats have not been adequately studied. We examined the records from 200 dogs and 65 cats that had received cardiopulmonary resuscitation for respiratory or cardiopulmonary arrest; none of the animals had been anesthetized or intubated at the time of arrest, and all had been hospitalized in a veterinary critical care facility. Cardiopulmonary arrest was found to be more common than respiratory arrest in dogs and cats. Hospital discharge rates for animals with cardiopulmonary arrest ranged from 4.1% for dogs to 9.6% for cats, and were consistent with those reported from studies of human beings with cardiopulmonary arrest. Hospital discharge rates for dogs and cats with respiratory arrest were 28% and 58.3%, respectively. PMID- 1639714 TI - Surgical treatment of dorsal cortical fractures of the third metacarpal bone in thoroughbred racehorses: 53 cases (1985-1989). AB - Between January 1985 and May 1989, 53 Thoroughbred horses (mean age 3.2 years) were surgically treated for dorsal cortical fractures of the third metacarpal bone (MC III). All horses were treated with cortical drilling through the fracture line (osteostixis). Diagnosis of the fractures was confirmed by xeroradiography. Lifetime racing records were obtained for all horses. Forty seven horses returned to racing after surgery (89%). The mean time between surgery and the first race was 6.8 months. Horses had a mean of 10.9 starts before surgery and 16.1 starts after surgery. The mean earnings per start before surgery was $6,459 and after surgery was $5,685. Of the 47 horses that raced after surgery, 70% raced at the same class or improved. Complications related to surgery were seen in 10 horses. Two horses had a second fracture of MC III at the same site, and were again treated by osteostixis, after which both horses returned to competition. Fractured drill bits were left in the MC III of 4 horses. One of these horses had catastrophic failure of MC III. Two horses developed subcutaneous infections and 2 horses had catastrophic failure of MC III in the surgically treated limb. Osteostixis appears to be an effective treatment for returning horses affected with dorsal cortical fractures to racing. PMID- 1639715 TI - Treatment of dogs with osteosarcoma by administration of cisplatin after amputation or limb-sparing surgery: 22 cases (1987-1990). AB - Twenty-two dogs with appendicular osteosarcoma were treated by amputation (n = 17) or limb-sparing surgery (n = 5). All dogs were given cisplatin (60 mg/m2 of body surface, IV) at 3-week intervals, beginning 1 week after surgery. Number of cisplatin treatments ranged from 1 to 6. Survival data for the 22 dogs were compared with survival data from a historical control group consisting of 162 dogs with appendicular osteosarcoma treated by amputation alone. Median survival time for the 22 dogs given cisplatin was estimated to be 46.4 weeks, and 1- and 2 year survival rates were estimated to be 45.5 and 20.9%, respectively. Survival time was significantly (P less than 0.0001) longer for treated dogs than for control dogs. Statistically significant relation was not found between survival time and number of cisplatin treatments. Three dogs were alive with no evidence of disease at the time of reporting. Of the remaining 19 dogs, 14 (73.4%) were euthanatized for problems documented to be related to metastases. Nine (47.4%) dogs were euthanatized because of bone metastases, and 5 (26.3%) were euthanatized because of pulmonary metastases. The proportion of dogs euthanatized because of bone metastases was significantly (P less than 0.0001) higher for treated than for control dogs. Median survival times for dogs developing bone and lung metastases were estimated to be 51.2 weeks and 21.2 weeks, respectively; however, this difference was not statistically significant. One local tumor recurrence was observed among dogs that had limb-sparing surgery. Significant difference in survival time was not observed between dogs that had limb-sparing surgery and dogs that underwent amputation. PMID- 1639716 TI - Characteristics of dogs admitted for treatment of cervical intervertebral disk disease: 105 cases (1972-1982). AB - Case histories of 105 dogs that were treated for cervical intervertebral disk disease (IVDD) were studied retrospectively. To compare with previous data, dogs were grouped by age, gender, and breed. Dogs were also grouped by clinical signs of disease, and by presence and location of radiologic change. The age range of cases of cervical IVDD was 1 to 13 years (mean, 6.3 years). Fifty-nine percent of dogs treated for cervical IVDD were females, but the proportion of diseased females was similar to females in total hospital admissions. Twenty-eight breeds of dogs were treated for cervical IVDD. Dachshunds and Beagles were significantly over represented (P less than or equal to 0.001). However, gender-breed interaction was not observed. Prevalence of radiologic evidence of disk disease was detected at the following levels of the vertebral column: C2-3, 29%; C3-4, 24%; C4-5, 21%; C5-6, 15%; C6-7, 9%; and C7-T1, 2%. Significant difference was not observed in prevalence of cervical IVDD affecting the first 4 disk spaces. However, prevalence of cervical IVDD at C7-T1 was significantly less than that involving the first 4 disk spaces (P less than 0.02), and the space at C6-7 was significantly less affected than were the first 3 spaces (P less than 0.08). Significant association was not evident between clinical signs (pain and neurologic deficits) and radiologic signs of IVDD, although neurologic deficits were more likely to be observed in association with radiologic signs than with signs of pain. PMID- 1639717 TI - Important curriculum content for baccalaureate allied health programs: a survey of deans. AB - The purpose of this study was to assist deans of baccalaureate-level schools of allied health professions to come to consensus on knowledge and skills that graduates should have over and above what is required for professional accreditation and credentialing, and prerequisite or cognate courses that may be utilized to develop them. An adaptation of the Delphi method was used in 1990 1991 to survey the deans of 74 institutional members of the Association of Schools of Allied Health Professions (ASAHP) offering programs at the bachelor's degree level. Three rounds of questionnaires were completed. The study concluded that there was consensus among the 54 deans who responded to the third questionnaire that 19 items of knowledge and skill are important for allied health students, and that 14 courses are important for the development of this knowledge and these skills. PMID- 1639718 TI - Allied health in a contemporary university: strategies for survival. PMID- 1639719 TI - Allied health and ethics: a grand rounds approach. PMID- 1639720 TI - AIDS and the responsibilities of academic health science centers: a case law approach. AB - The advent of AIDS and HIV infection has heightened administrator and faculty concern over providing and maintaining a safe environment for students in the health professions. Failure to provide this environment may result in litigation. Although case law on AIDS-related issues in higher education is sparse, court decisions on related issues are helpful in providing guidance on university responsibility. Case law indicates that if faculty provide appropriate supervision and give adequate instruction, including accepted safety practices, the courts will determine that the university has provided reasonable care to prevent student exposure to HIV. Other issues, related to HIV-positive students, demand that universities create carefully deliberated policies and procedures that do not discriminate against these individuals. This paper is the result of research on case law as it pertains to the potential legal issues of HIV and the university. PMID- 1639721 TI - Results of a summer academy to increase minority student access to allied health and other health professions. AB - To promote interest among incoming ninth grade students at two specialized high schools for health professions, and to help these students prepare for the upcoming high school experience and for pursuit of education and careers in allied health and other health professions, a three-week Summer Health Professions Academy was established. Students, 82.8% of whom were African American or Hispanic, participated in relevant didactic and experiential activities, with emphasis on allied health. Science, problem solving, communications, health career counseling, and allied health career exploration activities are described. Results of instruments administered both prior to and following the Academy indicated that students improved their abilities to analyze and solve science problems, and increased their knowledge of the nine primarily allied health professions emphasized during the program. Students also demonstrated heightened awareness of the factors that could impede their pursuit of allied health professions and other health careers. PMID- 1639722 TI - The impact of multiskilled practice on the job satisfaction of medical laboratory personnel. AB - This study examined practice patterns of medical laboratory personnel and investigated relationships of job-related variables and job satisfaction for single- and multiskilled practitioners. Data were collected from a random sample of American Society of Clinical Pathologist-registered practitioners in a five state region. Twenty-five percent of the sample was categorized as multiskilled. Regression analysis revealed that work performed had a significant positive contribution to overall job satisfaction for medical laboratory technicians (MLTs) and medical technologists. The strength of the relationship was weakest for multiskilled MLTs. Results support the contention that when jobs are redesigned, enriching them by adding tasks of increased complexity and challenge is possibly more effective than simply enlarging the jobs with lower- or parallel level tasks. PMID- 1639723 TI - Periodicity coding in the auditory system. AB - Periodic envelope fluctuations are a common feature of acoustic communication signals, and as a result of physical constraints, many natural, nonliving sound sources also produce periodic waveforms. In human speech and music, for example, periodic sounds are abundant and reach a high degree of complexity. Under noisy conditions these amplitude fluctuations may be reliable indicators of a common sound source responsible for the activation of different frequency channels of the basilar membrane. To make use of this information, a central periodicity analysis is necessary in addition to the peripheral frequency analysis. The present review summarizes our present knowledge about representation and processing of periodic signals, from the cochlea to the cortex in mammals, and in homologous or analogous anatomical structures as far as these exist and have been investigated in other animals. The first sections describe important physical and perceptual attributes of periodic signals, and the last sections address some theoretical issues. PMID- 1639724 TI - Estrogen influences auditory brainstem responses during the normal menstrual cycle. AB - We evaluated the impact of the menstrual cycle on auditory brainstem response (ABR) latency in nine normally cycling women. Subjects (age 23-40 years) using no hormonal therapy were recruited and underwent ABR testing during four different phases of the same menstrual cycle: early follicular (cycle days 1 to 3); mid cycle (cycle days 12 to 15); mid-luteal (cycle days 17 to 22), and premenstrual (cycle days 25-27). Cycles were verified by basal body temperature, and serum estrogen (E2), progesterone (P), and gonadotropin levels. A control group of nine women (age 23-40 years) on oral contraceptives (Nordette-28) was also studied four times during a pill cycle. Results show a significant increase in the latency of wave III and wave V peak latencies and in the I-V interpeak interval associated with a high estrogen state at the mid-cycle phase. No statistically significant variations in latency were found in the birth control pill group. These data suggest the existence of brainstem auditory neural pathways that are sensitive to fluctuations in E2 levels during the menstrual cycle. PMID- 1639725 TI - Effect of low level acoustic stimulation on temporary threshold shift in young humans. AB - To assess the effect of a low level acoustic stimulation on the susceptibility to noise, young human subjects were exposed to music at 70 dBA for 6 h per day during 9 days (training period). Noise sensitivity was assessed by measuring temporary threshold shift (TTS) induced by 105 dBSPL, 1/3 octave band noise at 2 kHz for 10 min. On the fifth day of the training period, a significant decrease of TTS was observed in the frequency range 3-3.5 kHz, in comparison with the baseline TTS obtained before being trained. As the training continued, the frequency range which showed a significant reduction of TTS expanded to 2-5 kHz. PMID- 1639726 TI - High frequency distortion products from the ears of two bat species, Megaderma lyra and Carollia perspicillata. AB - In two echolocating bat species, Megaderma lyra and Carollia perspicillata 2f1-f2 distortion products were measured acoustically in the outer ear canal for f1 frequencies between 5 and 95 kHz in an attempt to study nonlinear cochlear processes at high frequencies. Similar to other mammals, the input/output (I/O) functions of 2f1-f2 show non-monotonicities and notches at f1 levels between 40 70 dB SPL. The slope of the initial rise of the 2f1-f2 I/O functions increased with f1 frequency from 0.73 (5 kHz) to 1.41 (95 kHz) in Megaderma and from 0.66 (7.5 kHz) to 1.47 (95 kHz) in Carollia. With increasing f1 frequency the optimum frequency ratio f2/f1 in order to evoke maximum distortion level decreases from 1.18 (5 kHz) to 1.09 (95 kHz) in Megaderma and from 1.21 (7.5 kHz) to 1.11 (95 kHz) in Carollia. This is taken as indication of a general increase of the quality of tuning of the distortion generating mechanism with frequency. The f1 levels that were sufficient to elicit distortion levels of -10 dB SPL were used to construct iso-distortion threshold curves which lay on average 37.2 dB (Megaderma) and 33.9 dB (Carollia) above the neuronal threshold curves [Rubsamen et al., J. Comp. Physiol. A 163 (1988); Sterbing et al., Proc. 18th Gottingen Neurobiol. Conf. Thieme Verlag, Stuttgart (1990)] and roughly paralleled these. Highest distortion levels (40-50 dB SPL with f1 levels of 80 dB SPL) and lowest distortion thresholds were measured in the f1 frequency range of 10-30 kHz (Megaderma) and 15-30 kHz (Carollia).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639727 TI - Additivity of threshold elevations produced by disruption of outer hair cell function. AB - We present a simple model describing the additivity of hearing loss in the mammalian cochlea produced by disruption of the outer hair cell transduction processes. The validity of this model has been tested experimentally in the guinea-pig by inducing threshold elevations using two simultaneous cochlear manipulations, including acoustic overstimulation, two-tone suppression, low frequency acoustic biasing of the cochlear partition and electrical stimulation of the medial olivo-cochlear system of efferent fibres. The results of these experiments suggest that the model presented is an adequate description, within the measurement error of our experiments, of the hearing losses produced. PMID- 1639728 TI - Selectivity for temporal characteristics of sound and interaural time difference of auditory midbrain neurons in the grassfrog: a system theoretical approach. AB - The selectivity for temporal characteristics of sound and interaural time difference (ITD) was investigated in the torus semicircularis (TS) of the grassfrog. Stimuli were delivered by means of a closed sound system and consisted of binaurally presented Poisson distributed condensation clicks, and pseudo random (RAN) or equidistant (EQU) click trains of which ITD was varied. With RAN and EQU trains, 86% of the TS units demonstrated a clear selectivity for ITD. Most commonly, these units had monotonically increasing ITD-rate functions. In general, units responding to Poisson clicks, responded also to RAN and EQU trains. One category of units which showed strong time-locking had comparable selectivities for ITD with both stimulus ensembles. A second category of units showed a combined selectivity for temporal structure and ITD. These units responded exclusively to EQU trains in a nonsynchronized way. From the responses obtained with the Poisson click ensemble so-called Poisson system kernels were determined, in analogy to the Wiener-Volterra functional expansion for nonlinear systems. The kernel analysis was performed up to second order. Contralateral (CL) first order kernels usually had positive or combinations of positive and negative regions, indicating that the contralateral ear exerted an excitatory or combined excitatory-inhibitory influence upon the neural response. Ipsilateral (IL), units were characterized by first order kernels which were not significantly different from zero, or kernels in which a single negative region was present. A large variety of CL second order kernels has been observed whereas rarely IL second order kernels were encountered. About 35% of the units possessed nonzero second order cross kernels, which indicates that CL and IL neural processes are interacting in a nonlinear way. Units demonstrating a pronounced selectivity for ITD, were generally characterized by positive CL combined with negative IL first order kernels. Findings suggested that, in the grassfrog, neural selectivity for ITD mainly is established by linear interaction of excitatory and inhibitory processes originating from the CL and IL ear, respectively. Units exhibiting strong time-locking to Poisson clicks and RAN and EQU trains had significantly shorter response latencies than moderately time-locking units. In the first category of units, a substantial higher number of nonzero first and second order kernels was observed. It was concluded that nonlinear response properties, as observed in TS units, most likely have to be ascribed to nonlinear characteristics of neural components located in the auditory nervous system peripheral to the torus semicircularis. PMID- 1639729 TI - Immunochemical detection of glucocorticoid receptors within rat cochlear and vestibular tissues. AB - A monoclonal antibody, BuGR2, to liver glucocorticoid receptor sites was tested for its reactivity and specificity in inner ear tissue supernatants by an Enzyme Linked Immuno Sorbant Assay (ELISA) and a Western blotting technique. Results demonstrated that this antibody specifically recognized a protein of 93 kDa in inner ear supernatant fractions, which conformed to the reported molecular weights of the glucocorticoid receptor in other tissues. Antigenic sites were determined to be higher within cochlear supernatant fractions compared to vestibular supernatant fractions by ELISA. This anti-glucocorticoid receptor antibody combined with the quantitative ELISA provides a sensitive means to further investigate the inner ear glucocorticoid receptor system. PMID- 1639730 TI - Tone-induced stereocilia lesions as a function of exposure level and duration in the hamster cochlea. AB - The present study presents an atlas of the effects of 10 kHz tone exposures of different levels and durations on cochlear hair cells and their stereocilia in the Syrian golden hamster. Animals were sound exposed while under anesthesia. The exposure conditions were varied over an intensity range of 90-129 dB SPL; at the highest levels (126-129 dB SPL) the exposure periods were varied over a range of 30 min to 4 h. In animals with mild damage the lesions were commonly restricted to either the inner hair cells and/or the first row of outer hair cells; the order of damage susceptibility was IHC, OHC1, OHC2, OHC3. Damage to the second and third rows of outer hair cells were found only in animals with the severest lesions. Possible mechanisms underlying the row-specific distributions of these lesions and relative susceptibilities of the 4 rows of hair cells are discussed. PMID- 1639731 TI - Additivity of threshold losses produced by acute acoustic trauma. AB - We have previously [Patuzzi and Rajan, Hear. Res. 60, 165-177, 1992] formulated a model to describe how the threshold elevations produced by a variety of independent, short-term cochlear manipulations add when the manipulations are combined. The manipulations were presumed to affect only the 'active process' in the cochlea. The present report applied this model to the effects observed after acute acoustic trauma in normal-hearing guinea pigs and in guinea pigs with idiopathic threshold losses. Successive loud pure-tone exposures were presented to the normal-hearing guinea pigs, while only a single exposure was presented to the guinea pigs with idiopathic hearing losses. Various parameters of exposure and inter-exposure delays were used to create a variety of threshold elevations, and the total hearing losses observed in the various groups were compared to the total hearing losses predicted by the model. In most cases a statistically-valid 1:1 relationship was obtained between the predicted values and the observed values. In cases where the model's predictions were found not to fit the data, this appeared to be due to inclusion of data previously defined to be outside the scope of the model. When such data were excluded, there was good agreement between the model's predictions and the observed data. The model was further tested by comparing its predictions with data obtained in studies of acute noise trauma in chinchillas and humans by other researchers. The model's predictions were found to agree with these data as well. Thus, across a number of different types and conditions of exposures, the model appears to provide a very good description of the additivity of threshold losses produced by acute acoustic trauma. The generality of and constraints on the model are discussed. PMID- 1639732 TI - Loudness balance between electric and acoustic stimulation. AB - Binaural loudness balance between electric and acoustic stimulation is obtained in auditory brainstem implant listeners who had substantial acoustic hearing in one ear. The data are well described by a linear relationship between acoustic decibels and electric microamps. Based upon this linear relationship, we propose an exponential model of loudness growth in electric stimulation. The exponential model predicts that the loudness growth function can be determined solely by the threshold and the uncomfortable loudness level in electric stimulation. This prediction is consistent with previous psychophysical data on loudness functions. Implications of this finding for speech processor designs are discussed. PMID- 1639733 TI - High frequency radial movements of the reticular lamina induced by outer hair cell motility. AB - Recently, it was shown in cochlear explants from the guinea pig cochlea that electrokinetic motile responses of outer hair cells can induce radial and transverse motion of the reticular lamina. Here we demonstrate, that the radial component of these motions can be measured up to high frequencies (15 kHz). Cochlear explants were taken from guinea pig inner ears and exposed to a sinusoidal electric field. A double photodiode was used as a linear position detector with high spatial and temporal resolution to detect radial movements in the plane of the reticular lamina. The organ of Corti of the second, third and fourth cochlear turns was stimulated with frequencies of the electrical field between 0.5 Hz and 20 kHz. Sinusoidal movements of up to 15 kHz were recorded. At higher frequencies the signal-to-noise ratio became too small. The largest responses were measured at the three rows of outer hair cells. If the strength of the electrical field was 2 kV/m, into which the cochlear explants were placed, the amplitudes of outer hair cell movements were around 1 micron at 1 Hz and 10 nm at 10 kHz. Uncoupling of the outer hair cells from the tunnel of Corti and from the inner hair cells decreased the oscillations of inner hair cells but did not affect outer hair cells. The movements showed frequency dependent amplitudes like a complex low-pass filter but no best frequency was observed. PMID- 1639734 TI - Treatment satisfaction with an asthma management program: a "five"-year retrospective assessment. AB - The results of a five-year follow up of asthmatic children and parents who had completed a structured asthma management program are reported. The purpose of this project is (1) to assess treatment satisfaction, and (2) to identify which of the training components are considered most useful and/or which components are still being used by the participants. Eight families are interviewed. Results indicate that educational information and behavioral asthma management techniques are considered most useful. Improvement in asthma after program completion is reported and is attributed to the asthma management program, maturation, and medication. PMID- 1639735 TI - The effect of disodium cromoglycate against bronchial hyperresponsiveness in asthmatic children. AB - A long-term study of the effect of cromolyn sodium against bronchial hyperresponsiveness in asthmatic children is described. Cromolyn sodium powder (20 mg), as the capsule formulation, was inhaled by Spinhaler Turbohaler, tid, for three years. Histamine inhalation tests were performed every 6 months according to the standardized methods of the Japanese Allergy Congress. No other antiasthmatic therapy was given throughout the study except during an acute attack. Bronchial hyperresponsiveness decreased, and clinical symptoms improved throughout the trials. It is suggested that long-term use of cromolyn sodium reduces bronchial hyperresponsiveness concomitant with improved symptomatology in asthmatic children. PMID- 1639736 TI - Champ Camp: the Colorado Children's Asthma Camp experience. AB - To encourage children with asthma to enjoy outdoor activities without physical or psychosocial impairment, children's asthma camps are established throughout the country sponsored by organizations including local and state allergy societies. We wish to describe our Colorado "Champ Camp" experience as a model and reference for future similar efforts and to encourage networking by medical leadership for information sharing and guidelines development nationally. Statistics from parents' satisfaction surveys over 8 years demonstrate a positive influence on attitudes toward asthma and confidence to enter activities and sports with children without asthma. PMID- 1639737 TI - The potential role of anesthesia in status asthmaticus. PMID- 1639738 TI - Antiasthma drugs: key issues in clinical trial methodology. PMID- 1639739 TI - Alternative treatments for asthma: assessing the need. AB - Alternative treatments such as troleandomycin methotrexate, gold, and intravenous gamma globulin are sometimes considered for severe asthmatics to minimize the need for systemic corticosteroids and reduce adverse effects. These alternative therapies may also be associated with significant toxicity and expense. The ability to reduce corticosteroid use and the need for alternative treatment interventions in 125 pediatric patients at our institution were reviewed. Because corticosteroid requirements were reduced significantly, only 23 of 125 children evaluated were considered for treatment alternatives with only 10 receiving such therapy. This study emphasizes the importance of a thorough and comprehensive review of corticosteroid requirements and usage prior to initiating alternative approaches to treatment in moderate to severe asthmatics as well as in patients thought to be "steroid-dependent." PMID- 1639740 TI - A self-efficacy scale for children and adolescents with asthma: construction and validation. AB - A self-efficacy scale for children and adolescents with asthma between 10 and 18 years of age is described. A scale of 38 items was constructed and administered to 60 children and adolescents. A factor analysis of the results yielded a scale consisting of 22 items which can be divided into three subscales: factor one (24.8% of variance) measured efficacy expectations concerning medical treatment, factor two (10.3% of variance) measured efficacy expectations concerning the environment, and factor three (6.7% of variance) measured efficacy concerning problem-solving skills. Confirmation of several predicted conceptual relationships between the self-efficacy measures and other measures (Personality Questionnaire, Coping, Anxiety, Knowledge, Optimism, and Shame) provided preliminary evidence of construct validity. Further research and clinical applications are discussed. PMID- 1639741 TI - Response of negative symptoms of schizophrenia to neuroleptic treatment. AB - BACKGROUND: In view of the inconclusive reports in the literature about the response to neuroleptics of chronic schizophrenics with negative symptoms, the authors further evaluated this issue. METHOD: A sample of 30 ambulatory chronic schizophrenics meeting DSM-III-R criteria who had to a marked degree at least two negative symptoms of the five on the Scale for the Assessment of Negative Symptoms (SANS) received various therapeutic dosages of thiothixene for 3 months. The average dose was 26.75 mg/day. Subjects were periodically evaluated with the Brief Psychiatric Rating Scale, Negative Symptoms Rating Scale (a modified version of the SANS), and the Randt Memory Test. The time effect on treatment was calculated by repeated measures of analysis of variance. The relationship between the positive and negative symptoms was tested by an analysis of covariance. RESULTS: Both negative and positive symptoms improved with treatment. The negative symptoms tended to respond to treatment predominantly independently of the positive ones. At the end of the study, 63% (N = 19) of patients had improved moderately, 16% (N = 5) had improved slightly, and 20% (N = 6) had not improved. CONCLUSION: The data require further support from a long-term follow-up study that may show the extent to which these gains are maintained over time. PMID- 1639742 TI - Lack of association between fluoxetine and suicidality in bulimia nervosa. AB - BACKGROUND: The coincidence of major depressive disorder in bulimia nervosa ranges from 35% to 80%. Because of this comorbidity and because suicidality (suicidal acts and ideation) is an inherent part of depression, assessment of the risk of suicide in patients with bulimia nervosa is of considerable interest. METHOD: Data from United States Investigational New Drug double-blind, placebo controlled fluoxetine clinical trials in bulimia nervosa were analyzed comprehensively to assess the potential association between fluoxetine treatment and suicidality in 785 patients with DSM-III-R bulimia nervosa. Patients were predominantly women (98%), aged 17 to 63 years; of the randomly assigned patients, 16.9% exhibited 17-item Hamilton Rating Scale for Depression (HAM-D) total scores of 17 or greater at baseline (range, 0-31). Incidence of suicidality was analyzed by the incidence difference method. RESULTS: No fatal suicidal acts occurred; 9 (1.15%) of 785 patients made nonfatal attempts; 24 (3.06%) experienced emergent (text-defined) suicidal ideation. No statistically significant increases in the incidence of suicidal acts or suicidal ideation were observed among fluoxetine-treated compared with placebo-treated patients. A smaller percentage of fluoxetine-treated (2.0%) than placebo-treated (3.8%) patients experienced emergence of substantial suicidal ideation (change in baseline HAM-D Item 3 [suicide item] score of 0 or 1 to 3 or 4 during therapy). A statistically significantly greater proportion of fluoxetine-treated than placebo treated patients experienced improvement in suicidal ideation (decrease in HAM-D Item 3 score) from baseline to endpoint (p = .026). CONCLUSION: Analyses of the incidence of suicidal acts and suicidal ideation did not indicate an increased risk of suicidality in patients with bulimia nervosa treated with fluoxetine compared with those treated with placebo. PMID- 1639743 TI - Clozapine-induced agranulocytosis in a Native American: HLA typing and further support for an immune-mediated mechanism. AB - BACKGROUND: Approximately 30% of schizophrenic patients defined as treatment refractory significantly improve with clozapine. However, clozapine produces agranulocytosis in approximately 1% to 2% of patients in the United States. The mechanism of clozapine-induced agranulocytosis has not been established, but evidence suggests an immune-mediated mechanism. METHOD: Human leukocyte antigen (HLA) typing was performed in a native American with clozapine-induced agranulocytosis. RESULTS: Our findings support previous observations of a role of the HLA-B16, DR4, DQw3 haplotype in predicting susceptibility to agranulocytosis in clozapine-treated patients. CONCLUSION: We suggest that HLA typing of clozapine candidates may be useful for predicting the risk for clozapine-induced agranulocytosis. PMID- 1639744 TI - Granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment of clozapine induced agranulocytosis: a case report. AB - BACKGROUND: Granulocytopenia and agranulocytosis are severe side effects of clozapine therapy. Even if these side effects are detected early and if clozapine is discontinued, patients suffering from agranulocytosis are extremely endangered by infectious diseases for up to 3 to 4 weeks until hematologic recovery. Therefore, any treatment that reduces this critical time span would decrease the risks of clozapine treatment. METHOD: The case of a patient in whom severe agranulocytosis developed after 7 weeks of clozapine treatment is presented. RESULTS: After clozapine discontinuation, treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF), a glycoprotein that has been shown to stimulate the proliferation of precursor cells in the bone marrow and their differentiation into granulocytes and macrophages, was initiated. Under GM-CSF treatment, total granulocyte count rose from 63/cu mm to a value greater than 1500/cu mm within 5 days without complications or major side effects. CONCLUSION: This case report suggests that treatment with GM-CSF may lower the risks associated with clozapine-induced agranulocytosis and therefore may indirectly improve the safety of clozapine therapy. PMID- 1639745 TI - The efficacy of bupropion in winter depression: results of an open trial. AB - BACKGROUND: Seasonal affective disorder (SAD) refers to regularly recurring episodes of affective illness bearing a fixed relationship to season. Wintertime depression is its most widely recognized form. This study was undertaken to assess the efficacy of bupropion as a treatment for this disorder. METHOD: Fifteen consecutively presenting patients were treated with bupropion (200 to 400 mg/day). All met DSM-III-R criteria for major depression with a seasonal pattern. All were moderately to severely depressed. A modified version of the Hamilton Rating Scale for Depression (mHAM-D) including ratings of hypersomnia, increased appetite and carbohydrate craving, and weight gain was used to quantify the severity of illness. Up to 5 weeks of treatment was allowed before the subjects were categorized as nonresponders, partial responders, or responders. RESULTS: The mean +/- SD mHAM-D scores before and after treatment were 25.5 +/- 6.4 and 4.1 +/- 3.1, respectively. Ten (66.7%) of the subjects had a complete response to treatment (mHAM-D score less than or equal to 5). The other 5 (33.3%) had a partial response (mHAM-D score = 6-10). Five of the subjects had chronic pain and 3 had panic attacks restricted to episodes of depression. These problems resolved simultaneously with the symptoms of depression. CONCLUSION: The results of this open trial suggest that bupropion is an effective treatment for winter depression. However, controlled studies are required to confidently determine whether this is the case. PMID- 1639746 TI - Fluoxetine and suicidality. PMID- 1639747 TI - Paranoid psychosis, epidermoid tumor, and epilepsy: "symptomatic" psychosis or coincidence? PMID- 1639748 TI - Do monoamine oxidase inhibitors alter carbamazepine blood levels? PMID- 1639749 TI - Purification and characterization of beta-galactoside-binding proteins from Caenorhabditis elegans. AB - Two carbohydrate-binding proteins (subunit molecular masses, 32 and 16 kDa, respectively) were isolated for the first time from a nematode, Caenorhabditis elegans. They were specifically extracted with lactose and adsorbed on asialofetuin-Sepharose in the absence of a metal ion. Although these two proteins were co-eluted from a gel filtration column at a position corresponding to an apparent molecular size of 30 kDa under non-denaturing conditions, they could be separated by reversed-phase chromatography. The 32 kDa protein, the main component, was further characterized. Together with its solubility, saccharide specificity and metal independence, some other structural properties, including its amino acid composition, UV spectrum, and partial amino acid sequence, strongly suggested that the 32 kDa protein is a member of a class of soluble beta galactoside-binding lectins which had previously been only found in vertebrates. PMID- 1639750 TI - Genomic structure of human midkine (MK), a retinoic acid-responsive growth/differentiation factor. AB - Midkine (MK) is a product of a retinoic acid-responsive gene and a new heparin binding growth/differentiation factor. The coding sequence of human MK was located on 1.5 kb DNA segment. The structure of the cloned human MK gene was determined and compared with that of the mouse gene. The coding sequence was divided into 4 exons, and each exon and exon-intron boundary was highly homologous to those of the mouse. Furthermore, 170 bases in the upstream region of the putative transcription initiation sites and 3 blocks of 200-350 bases in regions further upstream were highly conserved. These sequences are likely to be involved in developmentally regulated expression of MK. PMID- 1639751 TI - Characterization of beta 1----4 galactosyltransferase purified from rat liver microsomes. AB - beta 1----4 Galactosyltransferase was purified from rat liver microsomes. Catalytic properties of the enzyme resembled those of previously purified soluble and membrane-bound beta 1----4 galactosyltransferases. The enzyme purified in the present study showed a major band around a molecular weight of 53,000 on SDS PAGE. The NH2-terminal sequence of the enzyme was determined up to the 20th residue. The sequence was identical to the amino acid sequence from Ala-13 to Lys 32 deduced from mouse beta 1----4 galactosyltransferase cDNA. These results suggest that most of the mature enzyme in rat liver microsomes is produced by removal of the NH2-terminal 12 amino acids from a precursor polypeptide. PMID- 1639752 TI - Subcellular distribution of glycolyltransferases in rodent liver and their significance in special reference to the synthesis of N-glycolyneuraminic acid. AB - The enzymic synthesis, transfer, and utilization of glycolyl-CoA (i.e. 2 hydroxyacetyl-CoA) have been studied in rat and mouse livers. On the one hand, these tissues contain the enzyme activities allowing the synthesis of glycolyl CoA from fatty acids (palmitate omega-hydroxylase, omega-hydroxypalmitoyl-CoA synthetase, and mitochondrial beta-oxidation of omega-hydroxypalmitoyl-CoA) and 3 hydroxypyruvic acid (oxidation by intact mitochondria). On the other hand, three types of glycolyltransferase activities can be demonstrated in rodent livers, depending on either carnitine, glucosamine, or glucosamine-6-phosphate. The subcellular distributions of these glycolyltransferase activities are similar to those of the corresponding acetyltransferase counterparts. Concerning carnitine glycolytransferase, the activity is widely distributed in the subcellular fractions, pointing out its occurrence in most cell compartments. By contrast, the glucosamine and glucosamine-6-phosphate glycolytransferase activities were located preferentially in the microsomal fraction. The condensation between glycolyl-CoA and glucosamine (or glucosamine-6-phosphate) raises the interesting question of the nature and the role of the resulting glycolylglucosamine molecule, especially in an alternative N-glycolylneuraminic acid synthesis pathway. PMID- 1639753 TI - The effect of amino acid deletion in subtilisin E, based on structural comparison with a microbial alkaline elastase, on its substrate specificity and catalysis. AB - Subtilisin from a wide variety of Bacillus species has been extensively investigated as a promising target for protein engineering. In this study, we analyzed the substrate specificity of B. subtilis subtilisin E based on the structure of a new alkaline elastase produced by the alkalophilic Bacillus strain Ya-B, which has very high elastolytic activity. Despite the high homology of the primary sequences of both enzymes (54% identical), alkaline elastase was found to lack four consecutive amino acids which, in subtilisin, have been shown by X-ray analysis to lie close to the P1 binding cleft. To examine the influence of such a deletion in subtilisin on its substrate specificity, we constructed several mutants missing four amino acids by site-directed mutagenesis. When assayed with synthetic peptides, elastin and casein as substrates, a mutant lacking Ser161 Thr162-Ser163-Thr164 showed considerably lower specific activity toward the substrates for subtilisin, and its substrate specificity approached that of alkaline elastase. The results indicate that the deletion in subtilisin E influences the catalytic efficiency as well as the P1 specificity, and that this region is, in part, responsible for the difference in specificity between the two enzymes. PMID- 1639754 TI - Essential histidine residue in 3-ketosteroid-delta 1-dehydrogenase. AB - The variation with pH of kinetic parameters was examined for 3-ketosteroid-delta 1-dehydrogenase from Nocardia corallina. The Vmax/Km profile for 4 androstenedione indicates that activity is lost upon protonation of a cationic acid-type group with a pK value of 7.7. The enzyme was inactivated by diethylpyrocarbonate at pH 7.4 and the inactivation was substantially prevented by androstadienedione. Analyses of reactivation with neutral hydroxylamine, pH variation, and spectral changes of the inactivated enzyme revealed that the inactivation arises from modification of a histidine residue. Studies with [14C]diethylpyrocarbonate provided support for the idea that the 1-2 essential histidine residues are essential for the catalytic activity of the enzyme. Dye sensitized photooxidation led to 50% inactivation of the enzyme with the decomposition of two histidine residues. This inactivation was also prevented by androstadienedione. Dancyl chloride caused a loss of the enzyme activity. Modifiers of glutamic acid, aspartic acid, cysteine, and lysine did not affect the enzyme activity. Butanedione and phenylglyoxal in the presence of borate rapidly inactivated the enzyme, indicating that arginine residues also have a crucial function in the active site. The data described support the previously proposed mechanism of beta-oxidation of 3-ketosteroid. PMID- 1639755 TI - Adsorption mode of exo- and endo-cellulases from Irpex lacteus (Polyporus tulipiferae) on cellulose with different crystallinities. AB - The adsorption mode of two highly purified cellulases, exo- and endo-type cellulases, from Irpex lacteus (Polyporus tulipiferae) was investigated by using pure cellulosic materials with different crystallinity as substrates. Adsorption of the two enzymes on the substrates was found to fit the Langmuir-type adsorption isotherm. Maximum amount of adsorbed enzyme obtained from the Langmuir plots showed an inverse correlation to the crystallinity of the substrate with both enzymes, and this value of endo-type cellulase was less dependent on the degree of crystallinity of substrates than that of exo-type cellulase, whose isotherms reached saturation in the range of low enzyme concentrations. The two enzymes showed relatively high affinities for all the substrates and their affinities increased with increasing crystallinity, but this tendency was less marked with endo-type cellulase than with exo-type one. In addition, large negative values of free energy change were observed on the adsorption of both enzymes, and the values became more negative with increasing crystallinity. Consequently, both cellulases showed high adsorption on crystalline cellulose and the adsorption process became smoother with increasing crystallinity. The adsorption of the two types of cellulases was endothermic with an increase in entropy, especially for amorphous cellulose, suggesting the occurrence of water release from the substrates during enzyme adsorption. In addition, the changes in thermodynamic parameters (delta H, delta S, and delta G) in adsorption of exo type cellulase were larger than in that of endo-type enzyme. PMID- 1639756 TI - Instability of F-actin in the absence of ATP: a small amount of myosin destabilizes F-actin. AB - The effects of the neutral salt concentration, pH, and coexistence of myosin on the denaturation of F-actin without ATP at low temperature were studied using the DNase I inhibition assay. The percent denaturation of F-actin gradually increased with a decrease in pH from 8.0 to 5.2, on incubation for 2 weeks in the presence of 50 mM KCl at 0 degrees C. This change was much faster in 0.5 M KCl and more than 75% of the F-actin became denatured on incubation for 1 week at pH 5.2. The buffer composition was found to exert a strong influence on the denaturation of F actin. That is, there was a tendency for the denaturation of F-actin at pH 6.0 to be faster in MES[2-(N-morpholino)ethanesulfonic acid]-NaOH buffer than in sodium phosphate buffer, the critical concentrations of actin in 0.5 M KCl being 0.31 mg/ml for MES-NaOH buffer and 0.15 mg/ml for sodium phosphate buffer. A sigmoidal relationship was found between the percent denaturation of F-actin and the KCl concentration added, the greatest change occurring at KCl concentrations between 0.25 and 0.75 M. The time courses of the denaturation of F-actin showed that the percent denaturation rose at first and that in time the rate of the increase decreased. In the case of pH 8.0 and 0.5 M KCl, it took about 1 week for the denaturation rate to begin to drop. The pH of 6.0 further promoted the instability of F-actin exposed to high KCl concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639757 TI - 13C-nuclear magnetic resonance of glycosphingolipids. AB - Spectra of 125 MHz 13C-nuclear magnetic resonance (NMR) of glycosphingolipids, GlcCer, GalCer, sulfatide, LacCer, and nLc4Cer have been studied, and the following results were obtained. (i) Signals of ring carbons of each sugar component are distributed in a wide field (50-110 ppm) and clearly separated. (ii) Chemical shifts of anomeric carbon (C1) and methylene carbon (C6) of sugars are far from those of other methine carbons of sugars and characteristic of sugar components, which makes it possible to identify each sugar component and its molar raito. (iii) The downfield shifts (about 6-9 ppm) of alpha-carbon signals involved in the glycosidic linkages and upfield shifts (about 1.5-2 ppm) of the neighboring beta-carbons, which are known as glycosylation shifts, could be observed. (iv) Characteristic shifts of aglycon signals caused by the presence of an OH group at the alpha-position of fatty acid were assigned. These observations are useful for the characterization of glycosphingolipid structures. PMID- 1639758 TI - A simple method for the release of asparagine-linked oligosaccharides from a glycoprotein purified by SDS-polyacrylamide gel electrophoresis. AB - A simple method for the release of oligosaccharides from glycoproteins separated by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) has been developed. Asialo alpha 1-acid glycoprotein, which was tritiated at the nonreducing terminal D galactopyranosyl residue by reduction with sodium borotritide after incubation with D-galactose oxidase, was used as a model compound. After electrophoretic separation of the glycoprotein, oligosaccharides were released by the use of a gas-phase hydrazinolysis apparatus. In the first method, the gel was stained with Coomassie Blue and the glycoprotein together with the gel was directly subjected to gas-phase hydrazinolysis after removal of water in a P2O5 desiccator. The recovery of released oligosaccharides was 25.9 +/- 2.4%, based on the amount of the glycoprotein loaded on the gel within the range of 3.5-28.5 micrograms. In the second method, the glycoprotein was electroblotted onto an Immobilon transfer membrane and was visualized by staining with Coomassie Blue. A small piece of the membrane with the corresponding band was cut out, dried in a desiccator and subjected to gas-phase hydrazinolysis. In this case, the recovery of released oligosaccharides was 15.2 +/- 1.0%. These procedures, particularly the first one, should be widely applicable for the isolation of oligosaccharides from glycoproteins separated by SDS-PAGE. PMID- 1639759 TI - Analysis of lectin properties with membrane ultrafiltration and high-pressure liquid chromatography. AB - A convenient method for the analysis of the binding properties of lectin with fluorogenic sugar chains is described. A lectin (concanavalin A or Datura stramonium agglutinin) was mixed with pyridylaminated sugar chains in buffer and the free chains obtained were isolated by membrane ultrafiltration. The amount of free sugar chains in the filtrate was measured by high-pressure liquid chromatography. The binding constants with the sugar chains, reaction kinetics, and other properties of these lectins were easily investigated. The method is simple and could be used to study the characteristics of any lectin in native form. PMID- 1639760 TI - Detection of large COOH-terminal domains processed from the precursor of Serratia marcescens serine protease in the outer membrane of Escherichia coli. AB - The Serratia marcescens serine protease gene encoding a 1,045-amino-acid precursor protein of 112 kDa directs excretion of the mature protease of ca. 58 kDa through the outer membrane of Escherichia coli. A typical signal peptide of 27 amino acids and a large COOH-terminal domain of the precursor are both functionally essential for the excretion of the mature protease into the medium. Sequence analysis of the fragment peptides of the mature protease as well as site directed mutagenesis indicated that the COOH-terminus of the mature enzyme was Asp645. By using the polyclonal antibody against the 112-kDa precursor protein, not only the intact precursor but also two proteins, C-1 (40 kDa) and C-2 (38 kDa), corresponding to the processed COOH-terminal domains were detected in the insoluble fraction of E. coli cells. Further fractionation by sucrose density gradient centrifugation showed that C-1 and C-2 were localized in the outer membrane. The NH2-terminal residues of C-1 and C-2 were determined to be Ala702 and Phe717, respectively. All these data suggest that the precursor is cleaved at three positions, between Asp645-Ser646, Glu701-Ala702, and Gly716-Phe717, probably by the self-processing activity in the normal excretion pathway through the outer membrane. PMID- 1639761 TI - Dihydrofolate reductase from Bacillus subtilis and its artificial derivatives: expression, purification, and characterization. AB - The Bacillus subtilis dihydrofolate reductase (DHFR) gene was expressed in Escherichia coli. The gene product was purified to homogeneity by Butyl Toyopearl, Toyopearl HW55, and DEAE-Toyopearl column chromatographies, and its molecular properties were compared to those of E. coli DHFR. The specific enzyme activity of the B. subtilis DHFR was 240 units/mg under the standard assay conditions, being about four times higher than that of the E. coli DHFR. Km for coenzyme NADPH was 20.7 microM, a value about three times larger than that of E. coli, whereas Km (1.5 microM) for the substrate, dihydrofolate, was similar to that of E. coli DHFR. This seems to reflect the low homology of the amino acid sequence in residues 61-88 of the two DHFRs where one of the NADPH binding sites is located [Bystrof, C. & Kraut, J. (1991) Biochemistry 30, 2227-2239]. Similar to the E. coli DHFR [Iwakura, M. et al. (1992) J. Biochem. 111, 37-45], the extension of amino acid sequences at the C-terminal end of the B. subtilis DHFR could be attained without loss of the enzyme function or decrease of the protein yield. Thus, the DHFR is useful as a carrier protein for expressing small polypeptides, such as leucine enkephalin, bradykinin, and somatostatin. PMID- 1639762 TI - mGK-6-derived true tissue kallikrein is synthesized, processed, and targeted through a regulated secretory pathway in mouse pituitary AtT-20 cells. AB - mGK-6-derived true tissue kallikrein was shown to be synthesized in mouse pituitary AtT-20 cells. This cell line, which is capable of processing other prohormones, only partially processed the proform of kallikrein to its active form, secreting it predominantly as the proform. The secretion of the active form was stimulated in response to a secretagogue, 8-bromo-cyclic AMP. These results imply that not only cellular elements capable of directing the processing of the proform to the active form and the intracellular transport of the kallikrein, but also a pathway that regulates the release of the active form may be present in the AtT-20 cells, thus the availability of this cell line for investigation of biosynthetic and secretory processes for tissue kallikrein in vivo being suggested. PMID- 1639763 TI - The trypsin-catalyzed activation of glutamate dehydrogenase purified from eel liver. AB - Eel liver glutamate dehydrogenase (GDH) [EC 1.4.1.3] was eightfold activated by trypsin and the molecular weight of the subunit of the native GDH decreased from 54,000 to 50,000. The C-terminal amino acid of both subunits was Thr. One peptide was released after proteolysis of the native GDH by trypsin and purified by anhydrotrypsin agarose and reversed-phase HPLC. The isolated peptide consisted of 39 amino acids and its amino acid sequence was as follows: H2NS-E-A-V-E-K-E-D-D-P N-F-F-K-M-V-E-G-F-F-D-K-G-A-A-I- V-E-N-K-L-V-E-E-D-L-K-T-R-COOH. The peptide contained the N-terminal of the native GDH and its molecular weight was calculated to be 4,413. We concluded that the trypsin-catalyzed activation was caused by release of this peptide from the native GDH. p-Chloromercuribenzoic acid inhibited the activity of the trypsin-treated GDH, but stimulated that of the native GDH. The response of trypsin-treated GDH to ADP and GTP was decreased compared with that of the native GDH. PMID- 1639764 TI - Chemical distribution of glycosphingolipids in third-instar larval organs of the blowfly, Calliphora vicina (Insecta: Diptera). AB - As a first approach to testing the working hypothesis that glycosphingolipids are functionally involved in the ontogeny of insects, their chemical distribution in larval organs was determined and any stadium-correlated differences documented. Selected organs, i.e., the fatbody, striated muscle, intestinal tract, salivary glands, imaginal discs, and central nervous system, were dissected from seven-day old larvae of the blowfly, Calliphora vicina, and their glycolipids isolated. Two dimensional, high-performance thin-layer chromatography was used to separate the neutral and acidic glycolipids of each organ. Significantly different total glycolipid component-patterns were obtained for the individual organs, whereby, except for a number of additional uncharacterized components in the intestinal tract, the neutral glycolipids of all organs were found to be qualitatively similar. However, major quantitative differences between the selected organs were found in their total glycolipid-carbohydrate contents, as well as the respective quantitative neutral glycosphingolipid-component distributions. The acidic glycolipids showed pronounced qualitative as well as quantitative organ-dependent variations. Whereas the highest proportion of uncharged glycolipids was characteristic of the fatbody, a high proportion of zwitterionic glycolipid components was observed to be typical of the central nervous system and imaginal discs, i.e., of organs persisting during larval life and throughout metamorphosis. Imaginal disc glycolipids were distinguished by their high content of acidic glycolipids, a putative reflection of the functional role of these glycoconjugates in regulated cell reorganization during metamorphosis. PMID- 1639765 TI - Purification and characterization of two isoforms of T-kininogens from rat liver microsomes. AB - T-Kininogen is one of the acute phase proteins, and is a precursor of T-kinin and a cysteine protease inhibitor. Two homologous T-kininogens (TI- and TII kininogens) were isolated from microsomal fraction of inflamed rat liver, by chromatographies on columns of DEAE-Sepharose CL-6B and DEAE-5PW and by affinity chromatography on a column of anti T-kininogen monoclonal antibody. The amino terminal amino acid sequences of the two microsomal pyridylethylated T-kininogens after pyroglutamyl aminopeptidase treatment were identical with those of TI- and TII-kininogens from inflamed rat plasma. Microsomal T-kininogens moved faster on SDS-PAGE after treatment with endoglycosidase H. The amounts of microsomal TI- and TII-kininogens in inflamed and non-inflamed rat liver were quantitated by immunoblotting of homogenates of liver microsomes using anti T-kininogen rabbit antiserum. The amounts of microsomal T-kininogens were increased in inflamed rat liver, but the ratio of the amounts of TI-kininogen to TII-kininogen was not different in the inflamed and non-inflamed rat liver. On the other hand, TII kininogen was not significantly detected in non-inflamed rat plasma. These results indicate that the secretion of one of the T-kininogens, TII-kininogen, into plasma may be prevented by some unknown mechanism. PMID- 1639766 TI - Sudden increase in speed of an actin filament moving on myosin cross-bridges of "mismatched" polarity observed when its leading end begins to interact with cross bridges of "matched" polarity. AB - Under in vitro movement assay conditions, actin filaments move about 10 times faster toward, than away from, the center of large bipolar thick filaments of molluscan smooth muscle. Using thick filaments isolated from the anterior byssus retractor muscle of Mytilus edulis, the two speed modes of movement were studied in detail. Some thick filaments crossed over each other on the surface of the assay chamber, allowing actin filaments that moved into the crossover region to transfer to other thick filaments. When an actin filament that had been moving in the low speed mode crossed over to another thick filament and the speed changed to fast, the entire actin filament started to move in the high speed mode at the moment of transfer of its leading end, leaving the trailing part still in contact with the original thick filament. This indicates that myosin cross-bridges interacting in the slow mode do not impose a significant load on the cross bridges interacting in the fast mode. Assuming the theoretical model of Tawada and Sekimoto [Biophys. J. 59, 343-356 (1991)], we suggest that the magnitude of force developed, as well as the speed of unloaded movement, differs greatly, depending on the orientation of the myosin cross-bridges. PMID- 1639767 TI - cDNA cloning and expression of rat tissue factor pathway inhibitor (TFPI). AB - Tissue factor pathway inhibitor (TFPI) is a factor Xa-dependent inhibitor for the factor VIIa-tissue factor complex. We isolated cDNA for rat TFPI by screening a lambda gt10 rat liver cDNA library. We determined the 1,228 bp nucleotide sequence, comprising a 88 bp 5' non-coding region, a 906 bp open reading frame, and a 234 bp 3' non-coding region, which encodes a protein of 302 amino acid residues. On Northern blot analysis of rat TFPI mRNA, rat TFPI mRNA was detected as two forms with different molecular sizes, 4.0 and 1.4 kb, which were expressed abundantly in heart, lung, kidney, and aortic endothelial cells. The homology of the amino acid sequence of rat TFPI with those of human and rabbit TFPI was found to be 60.7 and 57.4%, respectively. The lengths of the three tandem Kunitz-type inhibitor domains were strictly conserved not only among TFPI from the three species, but also among other proteins containing Kunitz-type inhibitor domains. The homology of the Kunitz-type domains in TFPI among the three species was 57, 86, and 69% in the 1st, 2nd, and 3rd domains, respectively. There was no significant difference in hydropathy profiles of TFPI from man, rabbit, and rat. PMID- 1639768 TI - Study on human erythrocyte thioltransferase: comparative characterization with bovine enzyme and its physiological role under oxidative stress. AB - Thioltransferase, an enzyme which catalyzes the thiol/disulfide exchange reaction in the presence of GSH, was purified to homogeneity on 15% SDS-PAGE from human (36,000-fold purification) and bovine (23,000-fold) erythrocyte hemolysates. These enzymes had similar properties in their monomeric structures (M(r) = 11,000) and broad specificities for substrates ranging from low-molecular disulfides (S-sulfocysteine, cystamine, and cystine) to protein disulfides (trypsin and insulin). They were highly sensitive to SH-reagents (monoiodoacetic acid and mercuric chloride), but were protected from inactivation by the presence of disulfides (GSSG, cystamine, and cystine). Phosphofructokinase and pyruvate kinase that had been inactivated by disulfides were reactivated effectively by the addition of thioltransferase with GSH. In addition, disulfides in membrane proteins of human erythrocytes that have been oxidatively damaged by diamide treatment were reduced to the SH-free form more effectively by incubation with thioltransferase. PMID- 1639769 TI - The p53 tumor suppressor protein, a modulator of cell proliferation. PMID- 1639770 TI - Reversible exposure of the pseudosubstrate domain of protein kinase C by phosphatidylserine and diacylglycerol. AB - The lipid activators of protein kinase C, phosphatidylserine and diacylglycerol, induce a reversible conformational change that exposes the auto-inhibitory pseudosubstrate domain of the enzyme. The pseudosubstrate domain of beta-II protein kinase C is cleaved after the first residue, arginine 19, by the endoproteinase Arg-C only when the kinase is bound to the activating lipid phosphatidylserine. Exposure of this residue is markedly enhanced by diacylglycerol. In contrast, the pseudosubstrate domain is not cleaved in the absence of lipids, when protein kinase C is bound to non-activating acidic lipids, when the kinase has autophosphorylated on the amino terminus, or after dilution of the activating lipids. This work reveals specificity in the interaction of protein kinase C with phosphatidylserine since only this phospholipid causes the specific conformational change detected in the regulatory domain of the enzyme, and demonstrates that allosteric regulators expose the intramolecular auto-inhibitory domain of a kinase. PMID- 1639771 TI - The multiple ADP/ATP translocase genes are differentially expressed during human muscle development. AB - The expression of the genes encoding the three isoforms of the human ADP/ATP translocase (T1, T2, and T3) has been analyzed at different stages of myogenic differentiation in an in vitro muscle cell system and compared with that in mature muscle. The results indicate that the three stages of muscle differentiation corresponding to myoblast proliferation, myotube formation, and mature muscle fibers are characterized by a different pattern of expression of the ADP/ATP translocase genes. In particular, the two T2-specific mRNAs are present at high, similar levels in myoblasts and myotubes and markedly decrease in amount in mature adult muscle. By contrast, the T3-specific mRNA is present in high amount in growing myoblasts, decreases markedly in myotubes, and is barely detectable in adult muscle. Finally, the T1-specific mRNA is present at a high level in adult muscle and is not detectable in either myoblasts or myotubes. Therefore, T1 gene expression appears to be a marker of a late stage in myogenesis. A parallel investigation of expression of the myosin heavy chain mRNA revealed absence of hybridization with the specific probe in RNA from proliferating myoblasts, a significant hybridization in myotube RNA, and a strong signal in adult muscle RNA. PMID- 1639772 TI - Presence of a repressor protein for testis-specific H2B (TH2B) histone gene in early stages of spermatogenesis. AB - The rat testis-specific TH2B histone gene assumes a hypomethylated chromatin structure at all stages of spermatogenesis. However, the TH2B mRNA level is very low in pre-meiotic spermatogenic cells and rises sharply in meiotic pachytene spermatocytes. The low level of TH2B mRNA in pre-meiotic spermatogenic cells appears to be a result of transcriptional repression of the gene by a pre-meiotic cell-specific protein which binds to a site between the TATA element and the transcription initiation site of TH2B gene. PMID- 1639773 TI - Interleukin-2 (IL-2) induces tyrosine kinase-dependent translocation of active raf-1 from the IL-2 receptor into the cytosol. AB - Stimulation of the interleukin-2 (IL-2) receptor results in phosphorylation and activation of cytosolic Raf-1 serine/threonine kinase. Herein, we report that enzymatically active Raf-1 is physically associated with the IL-2 receptor beta chain (p75) in T-cell blasts. Following stimulation with IL-2, Raf-1 dissociates from the IL-2 receptor complex and translocates to the cytosol. Genistein, a protein tyrosine kinase inhibitor, prevents the dissociation of enzymatically active Raf-1 from the ligand-stimulated IL-2 receptor complex. These data favor a model of IL-2 receptor activation in which an IL-2-activated protein tyrosine kinase phosphorylates the IL-2 receptor and/or receptor-bound Raf-1. Following tyrosine phosphorylation, enzymatically active Raf-1 dissociates from the IL-2 receptor and translocates into the cytosol. PMID- 1639774 TI - The 4F2 antigen heavy chain induces uptake of neutral and dibasic amino acids in Xenopus oocytes. AB - The 4F2 cell surface antigen is a disulfide-linked heterodimer induced during the process of cellular activation and expressed widely in mammalian tissues (Parmacek, M. S., Karpinski, B. A., Gottesdiener, K. M., Thompson, C. B., and Leiden, J. M. (1989) Nucleic Acids Res. 17, 1915-1931). The human heavy chain component, a type II membrane glycoprotein, has 29% identity to the amino acid transport-related protein encoded by the recently cloned rat D2 cDNA. We have demonstrated that Xenopus oocytes injected with in vitro transcribed cRNA from D2 take up cystine and dibasic and neutral amino acids (Wells, R. G., and Hediger, M. A. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 5596-5600). In the present study, we examine the role of the human 4F2 heavy chain in amino acid transport. In vitro transcribed 4F2 cRNA was injected into Xenopus oocytes which were assayed for the uptake of radiolabeled amino acids. Our results show that cRNA from 4F2 stimulates the uptake of dibasic and neutral amino acids into oocytes at levels up to 3-fold higher than for water-injected control oocytes. There is no demonstrable uptake of cystine. Uptake is saturable, with characteristics of high affinity transport, and inhibition data suggest that uptake occurs via a single transporter. Dibasic amino acids are taken up by both 4F2 and D2 cRNA-injected oocytes in a sodium-independent manner. In contrast, 4F2-induced but not D2 induced neutral amino acid uptake has a significant component of sodium dependence. Likewise, neutral amino acids in excess inhibit the 4F2-induced uptake of radiolabeled arginine but not leucine in a sodium-dependent manner. The 4F2-induced uptake we observe most likely represents the activity of a single transport system with some characteristics of systems y+, b0,+, and B0,+. We suggest that 4F2 and D2 represent a new family of proteins which induce amino acid transport with distinct characteristics, possibly functioning as transport activators or regulators. PMID- 1639775 TI - A transitional state of pro-urokinase that has a higher catalytic efficiency against glu-plasminogen than urokinase. AB - Plasminogen activation by single-chain urokinase-type plasminogen activator or pro-urokinase (pro-UK) is accompanied by the generation of two-chain urokinase (UK) by plasmin which provides a positive feedback. In the present study, the time course of the activation of Glu-plasminogen and of Lys-plasminogen (10 microM) by pro-UK (1.0 nM) was studied. In the presence of native plasminogen (Glu-plasminogen), three distinct phases with different rates of plasmin generation were observed. The initial phase was slow and corresponded to the intrinsic activity of pro-UK as reflected by the activity of a plasmin-resistant mutant (Lys158----Ala). This was followed by a second phase which had the most rapid rate. The third phase had a plasminogen activation rate which was significantly slower than the second and paralleled the rate of activation by UK (1.0 nM). The second phase coincided with the time at which there was only about 50% conversion of pro-UK to UK, whereas the final phase coincided with essentially complete conversion. In the presence of fibrin fragment E-2 (20 microM), previously shown to strongly promote plasminogen activation by pro-UK, the identical phenomenon was observed, but at one-tenth the concentration of pro UK. The most rapid rate of plasmin generation again coincided with transitional (25-60%) pro-UK to UK conversion. To further examine this phenomenon, the rate of pro-UK to UK conversion was controlled by using kallikrein in the presence of a plasmin inhibitor. In this experiment, the activation of Glu-plasminogen bound to solid-phase fibrin was measured. A similar three-phase sequence was observed, the highest rate of plasmin generation coinciding with about 45% conversion of pro-UK to UK. A mechanism for this transitional state phenomenon was postulated based on the established significantly higher affinity of pro-UK than of UK for Glu plasminogen. This exceptional property for a proenzyme may enable a transient activity to be generated during the transition from pro-UK to UK corresponding to the more favorable KM of pro-UK and the kcat of UK. This hypothesis was supported by the results from experiments in which Lys-plasminogen was substituted for the Glu form. No transitional state activity was observed, consistent with the relatively high KM of pro-UK against Lys-plasminogen. PMID- 1639776 TI - Adenine affects the structure and stability of telomeric sequences. AB - Adenine occurs in the strand containing repeated G clusters in the telomeric DNA of a variety of organisms, including that of humans. The role of adenine has been investigated by constructing two sets of oligonucleotides each with one, two, or four copies of the telomeric sequence dTTTAGGG together with a control sequence in which T replaces the A residue, dTTTTGGG. Comparison of the stability and spectral properties of these two sequences in the presence of Na+ or K+ affords a basis for defining the role of adenine in these structures. In Na+, the A residue stabilizes the structure formed by each oligomer significantly, presumably by a base-pairing interaction with T. In K+, by contrast, there is little difference in stability. In two- and four-copy oligomers, the A sequence has a different structure from its T analog, as detected by CD spectroscopy. In the presence of either Na+ or K+, the tetraplexes of A and T interact with intercalators. PMID- 1639777 TI - Analysis of two novel classes of plant antifungal proteins from radish (Raphanus sativus L.) seeds. AB - Two novel classes of antifungal proteins were isolated from radish seeds. The first class consists of two homologous proteins (Rs-AFP1 and Rs-AFP2) that were purified to homogeneity. They are highly basic oligomeric proteins composed of small (5-kDa) polypeptides that are rich in cysteine. Both Rs-AFPs have a broad antifungal spectrum and are among the most potent antifungal proteins hitherto characterized. In comparison with many other plant antifungal proteins, the activity of the Rs-AFPs is less sensitive to the presence of cations. Moreover, their antibiotic activity shows a high degree of specificity to filamentous fungi. The amino-terminal regions of the Rs-AFPs show homology with the derived amino acid sequences of two pea genes specifically induced upon fungal attack, to gamma-thionins and to sorghum alpha-amylase inhibitors. The radish 2S storage albumins were identified as the second novel class of antifungal proteins. All isoforms inhibit growth of different plant pathogenic fungi and some bacteria. However, their antimicrobial activities are strongly antagonized by cations. PMID- 1639778 TI - Substrate specificity of a CoA-dependent stearoyl transacylase from bovine testis membranes. AB - We identified a CoA-dependent stearoyl transacylase activity in bovine testis membranes, then examined the enzyme's specificity in mixed micelle systems containing the neutral detergent Triton X-100. The enzyme transferred stearoyl groups from a variety of phospholipids to sn-2-arachidonoyl lysophosphatidic acid (lysoPA), but showed very little palmitoyl transacylase activity. Its ability to transfer stearoyl groups was both donor- and acceptor-dependent. For example, it used weakly acidic phospholipids, such as sn-1-stearoyl-2-acyl species of phosphatidylinositol (PI), as donors, but did not use phosphatidylinositol-4,5 bisphosphate or sn-1-stearoyl-2-arachidonoyl phosphatidylcholine. Moreover, it used sn-2-acyl species of lysoPA and sn-2-arachidonoyl lysoPI as acceptors but did not use sn-2-arachidonoyl species of lysophosphatidylserine, lysophosphatidylethanolamine, or lysophosphatidylcholine. When taken together, our results raise the possibility that sn-1-stearoyl-2-acyl species of PI may be the primary acyl donors in the transacylase reaction in vivo, while sn-2-acyl species of lysoPA may be the primary acyl acceptors. Available evidence suggests that the PA that is formed may subsequently be converted into PI, but the metabolic fate of the other reaction product, sn-2-acyl lysoPI, remains to be determined. PMID- 1639779 TI - Characterization and nucleotide binding properties of a mutant dihydropteridine reductase containing an aspartate 37-isoleucine replacement. AB - Kinetic constants for the interaction of NADH and NADPH with native rat dihydropteridine reductase (DHPR) and an Escherichia coli expressed mutant (D-37 I) have been determined. Comparison of kcat and Km values measured employing quinonoid 6,7-dimethyldihydropteridine (q-PtH2) as substrate indicate that the native enzyme has a considerable preference for NADH with an optimum kcat/Km of 12 microM-1 s-1 compared with a figure of 0.25 microM-1 s-1 for NADPH. Although the mutant enzyme still displays an apparent preference for NADH (kcat/Km = 1.2 microM-1 s-1) compared with NADPH (kcat/Km = 0.6 microM-1 s-1), kinetic analysis indicates that NADH and NADPH have comparable stickiness in the D-37-I mutant. The dihydropteridine site is less affected, since the Km for q-PtH2 and K(is) for aminopterin are unchanged and the 14-26-fold synergy seen for aminopterin binding to E.NAD(P)H versus free E is decreased by less than 2-fold in the D-37-I mutant. No significant changes in log kcat and log kcat/Km versus pH profiles for NADH and NADPH were seen for the D-37-I mutant enzyme. However, the mutant enzyme is less stable to proteolytic degradation, to elevated temperature, and to increasing concentrations of urea and salt than the wild type. NADPH provides maximal protection against inactivation in all cases for both the native and D-37 I mutant enzymes. Examination of the rat DHPR sequence shows a typical dinucleotide binding fold with Asp-37 located precisely in the position predicted for the acidic residue that participates in hydrogen bond formation with the 2' hydroxyl moiety of all known NAD-dependent dehydrogenases. This assignment is consistent with x-ray crystallographic results that localize the aspartate 37 carboxyl within ideal hydrogen bonding distance of the 2'- and 3'-hydroxyl moieties of adenosine ribose in the binary E.NADH complex. PMID- 1639780 TI - Isolated cardiomyocytes in conjunction with NMR spectroscopy techniques to study metabolism and ion flux. AB - To distinguish cellular from vascular responses to physiological and pathophysiological stimuli, we developed methods to perform NMR spectroscopy on isolated ventricular cardiomyocytes. Isolated adult rat cardiomyocytes, placed in agarose beads and superfused with phosphate-free buffer (Media 199 (GIBCO 400 1100) gassed with 95% O2, 5% CO2), were used to evaluate a variety of cellular processes during different pharmacological and physiological interventions. Bioenergetic function was monitored with 31P NMR. Intermediary metabolism, gluconeogenesis, and glycolysis were monitored with 13C NMR. Sodium flux was monitored with 23Na NMR. Calcium flux was monitored with 19F NMR in conjunction with an intracellular calcium-chelating agent, 5F-1,2-bis(2-amino-phenoxy)ethane N,N,N',N'-tetraacetic acid. Creatine kinase kinetics (forward rate constant (Kf) and flux of phosphocreatine to ATP) were estimated with 31P NMR saturation transfer data. Various combinations of NMR parameters were monitored simultaneously so that the interaction of metabolism and ion flux could be evaluated. We have demonstrated that it is possible to simultaneously monitor a variety of cellular processes in intact heart cells in real time, without the confounding influences of perfusion, contractile function, and extrinsic blood borne neurohumoral agents. This model will be useful for longitudinal studies of myocyte metabolism and ion flux. PMID- 1639781 TI - Mechanism of loss of thermodynamic control in mitochondria due to hyperthyroidism and temperature. AB - Incubation of normal mitochondria at 45 degrees C results in increases of respiration and of total apparent proton conductance (TAPC, respiration/proton motive force) and in an upward shift of the flow-force relationships. Similar effects are observed during operation of the redox proton pumps at different sites of the respiratory chain. These effects are accompanied by an almost equivalent increase of the passive proton conductance (PPC, proton leakage/proton motive force). In mitochondria from 3,3,5-triiodo-L-thyronine (T3)-treated rats there are also increases of respiration and of TAPC and an upward shift of flow force relationships, more pronounced at the level of the cytochrome oxidase proton pump. However, at variance from the incubation at 45 degrees C, in mitochondria from T3-treated rats there is only a slight increase of PPC. Addition of bovine serum albumin to normal mitochondria incubated at 45 degrees C results in a marked depression of TAPC in the nonlinear range of the flow-force relationships. An equivalent effect is not observed in mitochondria from T3 treated rats. The experimental results have been compared with computer simulations obtained on the basis of a chemiosmotic model of energy transduction. The increase of TAPC following incubation at high temperature is apparently due to changes of the proton conductance mainly at the level of PPC, while the increase of TAPC following T3 administration is rather due to changes presumably at the level of the redox or ATPase proton pumps. PMID- 1639782 TI - Structure of the gene and its retinoic acid-regulatory region for murine J6 serpin. An F9 teratocarcinoma cell retinoic acid-inducible protein. AB - We have recently reported a protein sequence deduced from the retinoic acid (RA) inducible mRNA J6 as a novel serine protease inhibitor (serpin). In this study we have reported that the J6 serpin gene is 7.7 kilobases in length and consists of five exons with an additional option. Comparison of the organization of the J6 gene and other serpin genes reveals that the structure of the J6 gene is different from the reported four serpin gene groups. Nonetheless, intron B of the J6 gene and members of the alpha-antitrypsin gene group are at the equivalent positions, suggesting that the J6 gene is more closely related to the members of alpha-anti-trypsin gene group than other serpins. To identify the RA response region, we have further examined the nucleotide sequence of the 1-kilobase 5' flanking region of the J6 gene. The DNA sequence from position -1050 to -738 is essential for the gene activation by RA as revealed by the stable transfection experiments. Within this region, present are four GA-GATAG motifs which are the known binding sites for GATA transcription factor family. Interestingly, there is a potential heat shock element with alternate arrays of blocks XGAAX and XTTCX spanning from -88 to -59, indicating that the J6 gene perhaps is heat-inducible. PMID- 1639783 TI - Intrinsic fluorescence changes and rapid kinetics of the reaction of thrombin with hirudin. AB - Stopped-flow fluorescence spectroscopy has been used to study the reaction of human alpha-thrombin with recombinant hirudin variant 1 (rhir) at 37 degrees C and an ionic strength of 0.125 M. A 35% enhancement in intrinsic fluorescence accompanied formation of the thrombin-rhir complex. Over one third of this enhancement corresponded to a structural change that could be induced by binding of either the NH2-terminal fragment (residues 1-51) or the COOH-terminal fragment (residues 52-65) of rhir. Three kinetic steps were detected for reaction of thrombin with rhir. At high rhir concentrations (greater than or equal to 3 microM), two intramolecular steps with observed rate constants of 296 +/- 5 s-1 and 50 +/- 1 s-1 were observed. By using the COOH-terminal fragment of rhir as a competitive inhibitor, it was possible to obtain an estimate of 2.9 x 10(8) M-1 s 1 for the effective association rate constant at low rhir concentrations. At higher ionic strengths, this rate constant was lower, which is consistent with the formation of the initial complex involving an ionic interaction. The mechanism for the reaction of both the COOH- and NH2-terminal fragments of rhir appeared to involve two steps. When thrombin was reacted with the COOH-terminal fragment at high concentrations (greater than or equal to 6 microM), the bimolecular step occurred within the dead time of the spectrometer and only one intramolecular step, with a rate constant of 308 +/- 5 s-1 was observed. At concentrations of NH2-terminal fragment below 50 microM, its binding to thrombin appeared to be a bimolecular reaction with an association rate constant of 8.3 x 10(5) M-1 s-1. In the presence of saturating concentrations of the COOH-terminal fragment, a 1.7-fold increase in this rate constant was observed. At concentrations of NH2-terminal fragment greater than 50 microM, biphasic reaction traces were observed which suggests a two-step mechanism. By comparing the reaction amplitudes and dissociation constants observed with rhir and its COOH terminal fragment, it was possible to obtain approximate estimates for the values of the rate constants of different steps in the formation of the rhir-thrombin complex. PMID- 1639784 TI - Kinetics of leucine transport in brush border membrane vesicles from lepidopteran larvae midgut. AB - The kinetics of K(+)-leucine cotransport in the midgut of lepidopteran larvae was investigated using brush border membrane vesicles. Initial rate (3 s) of leucine uptake was determined under experimental conditions similar to those occurring in vivo, i.e. in the presence of delta psi much greater than 0 (inside negative) and a delta pH of 1.4 units (7.4in/8.8out). Leucine and K+ bind to the carrier according to a sequential mechanism, and the binding of one substrate changed the dissociation constant for the other substrate by a factor of 0.15. Both trans-K+ and trans-leucine were mixed-type inhibitors of leucine uptake. Moreover, a portion of total leucine uptake was K+ independent, and it was competitively inhibited by trans-leucine. We interpret the trans inhibitory effects to mean that the partially loaded K+ only form is virtually unable to translocate across the membrane, whereas the binary complex carrier, leucine, can isomerize from the trans to the cis side of the membrane. However, the K(+)-independent leucine uptake occurs with a Keq greater than 1, i.e. the efflux route through the partially loaded leucine only form is slower than the rate of isomerization of the unloaded carrier from trans to cis side. Taken together, these results suggest a model in which transport occurs by an iso-random Bi Bi system. Since K+ does not act as a pure competitive activator, this model is different from that proposed for most of the Na(+)-linked solutes transport agencies and may be related to the broadening of the cation specificity of the amino acid transporters in lepidopteran larvae. PMID- 1639785 TI - Roles of FAD and 8-hydroxy-5-deazaflavin chromophores in photoreactivation by Anacystis nidulans DNA photolyase. AB - DNA photolyase from the cyanobacterium Anacystis nidulans contains two chromophores, flavin adenine dinucleotide (FADH2) and 8-hydroxy-5-deazaflavin (8 HDF) (Eker, A. P. M., Kooiman, P., Hessels, J. K. C., and Yasui, A. (1990) J. Biol. Chem. 265, 8009-8015). While evidence exists that the flavin chromophore (in FADH2 form) can catalyze photorepair directly and that the 8-HDF chromophore is the major photosensitizer in photoreactivation it was not known whether 8-HDF splits pyrimidine dimer directly or indirectly through energy transfer to FADH2 at the catalytic center. We constructed a plasmid which over-produces the A. nidulans photolyase in Escherichia coli and purified the enzyme from this organism. Apoenzyme was prepared and enzyme containing stoichiometric amounts of either or both chromophores was reconstituted. The substrate binding and catalytic activities of the apoenzyme (apoE), E-FADH2, E-8-HDF, E-FAD(ox)-8-HDF, and E-FADH2-8-HDF were investigated. We found that FAD is required for substrate binding and catalysis and that 8-HDF is not essential for binding DNA, and participates in catalysis only through energy transfer to FADH2. The quantum yields of energy transfer from 8-HDF to FADH2 and of electron transfer from FADH2 to thymine dimer are near unity. PMID- 1639786 TI - Relations between factor VIIa binding and expression of factor VIIa/tissue factor catalytic activity on cell surfaces. AB - The kinetics of the binding of rVIIa to cell surface tissue factor (TF) and the resultant expression of VIIa/TF activity were studied. Binding of 125I-rVIIa (10 nM) to cell surface TF required 30-60 min for saturation, whereas VIIa/TF activity was fully expressed toward factor X (F X) on intact monolayers after only 1 min of incubation. At the time only 10-20% of the total VIIa TF complexes present at saturation had formed. Freeze-thawing the monolayers before assay increased VIIa/TF activity up to 30-fold, and the time course of its expression was similar to that of TF-specific binding of VIIa to the monolayers. Equilibrium binding revealed a single high affinity binding class of TF sites on intact monolayers for rVIIa with a Kd of 1.6 nM. Experiments with active-site inhibited rVIIa yielded evidence for two populations of VIIa. TF complexes on intact monolayers: (1) a minor population (less than 20%) that formed within 1 min of incubation and accounted for all VIIa/TF activity toward F X present on the intact monolayers, and (2) a major population that was inactive toward F X on intact monolayers but which was fully active after the monolayers were lysed. Tissue factor pathway inhibitor (TFPI).F Xa complexes inhibited the VIIa/TF activity of the first population, i.e. of the complexes active on intact monolayers, half maximally at a concentration of 0.2 nM TFPI. TFPI/Xa also bound to the second population of VIIa.TF complexes on intact monolayers and inhibited their expression of VIIa/TF activity following cell lysis with a half-maximal inhibitory concentration of 2.0 nM. The potential physiologic implications of these findings are discussed. PMID- 1639788 TI - Determination of residue specificity in the EF-hand of troponin C for Ca2+ coordination, by genetic engineering. AB - Utilizing protein engineering of troponin C (TnC), combined with the physiology of skinned fibers, the present study sought to delineate the mechanisms for metal ion coordination and sensitivity in the sites (EF-hands) that execute the Ca2+ switch for contraction. A total TnC-encoding gene comprising multiple target sequences for restriction enzymes was synthesized, furnishing a pliant molecular handle to manipulate sites I and II in the NH2 terminus of the protein. Of the six positions (X, Y, Z, -Y, -X, and -Z) essential for metal ion chelation in a typical EF-hand, invariably the X position has aspartate, and -Z position has glutamate. In the X position of site II, mutation of aspartate for either glutamate (gamma-carboxylate) or asparagine (same side chain length as aspartate) yielded functionally inactive proteins with concomitantly diminished Ca2+ binding capacity. Similarly, in -Z position (site I), neither aspartate nor glutamine were compatible in exchange for the conserved glutamate. In contrast, for the Y coordinate of site II, a preference for asparagine comparable to that for wild type aspartate was detected, but glutamate was impermissible. Evidently, physicochemical and steric factors both are critical in governing the mechanism for metal ion chelation in TnC in a physiological milieu. Furthermore, the findings manifest that the quaternary structure of hydrated TnC restrains the EF hands during on-off operation of the Ca2+ switch. PMID- 1639787 TI - Molecular cloning and characterization of (R)-3-hydroxybutyrate dehydrogenase from human heart. AB - The complete amino acid sequence of human heart (R)-3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) has been deduced from the nucleotide sequence of cDNA clones. This mitochondrial enzyme has an absolute and specific requirement of phosphatidylcholine for enzymic activity (allosteric activator) and is an important prototype of lipid-requiring enzymes. Despite extensive studies, the primary sequence has not been available and is now reported. The mature form of the enzyme consists of 297 amino acids (predicted M(r) of 33,117), does not appear to contain any transmembrane helices, and is homologous with the family of short-chain alcohol dehydrogenases (SC-ADH) (Persson, B., Krook, M., and Jornvall, H. (1991) Eur. J. Biochem. 200, 537-543) (30% residue identity with human 17 beta-hydroxysteroid dehydrogenase). The first two-thirds of the enzyme includes both putative coenzyme binding and active site conserved residues and exhibits a predicted secondary structure motif (alternating alpha-helices and beta-sheet) characteristic of SC-ADH. Bovine heart peptide sequences (174 residues in nine sequences determined by microsequencing) have extensive homology (89% identical residues) with the deduced human heart sequence. The C-terminal third (Asn-194 to Arg-297) shows little sequence homology with the SC-ADH and likely contains elements that determine the substrate specificity for the enzyme including the phospholipid (phosphatidylcholine) binding site(s). Northern blot analysis identifies a 1.3-kilobase mRNA encoding the enzyme in heart tissue. PMID- 1639789 TI - Evidence that Caenorhabditis elegans 32-kDa beta-galactoside-binding protein is homologous to vertebrate beta-galactoside-binding lectins. cDNA cloning and deduced amino acid sequence. AB - We have cloned a full-length cDNA for a beta-galactoside-binding protein with a relative molecular mass of 32 kDa (32-kDa GBP), recently purified from a nematode, Caenorhabditis elegans (Hirabayashi, J., Satoh, M., Ohyama, Y., and Kasai, K. (1992) J. Biochem. 111, 553-555). The clone contained a single open reading frame encoding 279 amino acids, including the initiator methionine. Significant sequence homology to metal-independent beta-galactoside-binding lectins (25-30% identities), which had previously been found only in vertebrates, was observed. Moreover, the nematode 32-kDa GBP proved to have a unique polypeptide architecture; that is, it is composed of two tandemly repeated homologous domains, each consisting of about 140 amino acids. The internal homology was about 32%. Thus, this protein is constructed with a duplicated fundamental unit which is similar to the subunit of vertebrate 14-kDa lectins. In spite of the extreme phylogenic distance between nematodes and vertebrates (divergence greater than 6 x 10(8) years ago), both of the two repeated domains of the nematode 32-kDa GBP retained most of the amino acid residues conserved in vertebrate lectins. This means that members of the metal-independent animal lectin family are distributed much more widely than had been believed: from nematodes to vertebrates. The implication is that proteins belonging to this family have fundamental roles which are not restricted to vertebrates but are common to almost all animals. PMID- 1639790 TI - Resonance Raman and magnetic circular dichroism studies of reduced [2Fe-2S] proteins. AB - The structural and electronic properties of the [2Fe-2S] clusters in reduced putidaredoxin, Spinacea oleracea ferredoxin, and Clostridium pasteurianum [2Fe 2S] ferredoxin have been investigated by resonance Raman and variable temperature magnetic circular dichroism spectroscopies. Both techniques are shown to provide diagnostic fingerprints for identifying [2Fe-2S]+ clusters in more complex multicomponent metalloenzymes. The Fe-S stretching modes of oxidized and reduced putidaredoxin are assigned via 34S and D2O isotope shifts and previous normal mode calculations for adrenodoxin (Han, S., Czernuszewicz, R. S., Kimura, T., Adams, M. W. W., and Spiro, T. G. (1989) J. Am. Chem. Soc. 111, 3505-3511). The close similarity in the resonance Raman spectra of reduced [2Fe-2S] centers, in terms of both the vibrational frequencies and enhancement profiles of the Fe-S stretching modes, permits these assignments to be generalized to all clusters of this type. Modes primarily involving Fe(III)-S(Cys) stretching are identified in all three reduced [2Fe-2S] proteins, and the frequencies are rationalized in terms of the conformation of the cysteine residues ligating the Fe(III) site of the localized valence reduced cluster. D2O isotope shifts indicate few, if any, amide NH-S hydrogen bond interactions involving the cysteines ligating the Fe(III) site. Preliminary resonance Raman excitation profiles suggest assignments for the complex pattern of electronic bands that comprise the low temperature magnetic circular dichroism spectra of the reduced proteins. S----Fe(III) and Fe(II)----S charge transfer, Fe d-d, and Fe(II)----Fe(III) intervalence bands are identified. PMID- 1639791 TI - Genistein inhibits protein histidine kinase. AB - Protein histidine kinase was prepared from whole cell extracts of the yeast, Saccharomyces cerevisiae. The enzyme was assayed using either histone H4 or a synthetic peptide corresponding to residues 70 to 102 of histone H4 as an in vitro substrate. With either substrate, both genistein and its solvent, dimethyl sulfoxide (Me2SO), inhibited protein histidine kinase. Me2SO alone gave a cooperative dose-response curve, with inhibition changing from almost zero below 10% Me2SO to 80% at 20% Me2SO with either substrate. Genistein gave a simple dose response curve with 50% inhibition of protein histidine kinase at 110 microM genistein. In experiments with protein histidine kinase, genistein was a noncompetitive inhibitor with respect to ATP, histone H4 or the synthetic peptide, although, in the case of the synthetic peptide, the data were also consistent with competitive inhibition. These data gave Km values for both ATP and histone H4 of 15 microM, in satisfactory agreement with previously reported values (Huang, J., Wei, Y., Kim, Y., Osterberg, L., and Matthews, H. R. (1991) J. Biol. Chem. 266, 9023-9031). The Km for the synthetic peptide was 80 microM. The KI values were 270 or 310 microM measured with histone H4 or the synthetic peptide as substrate, respectively. While these KI values are relatively high, relative to published KI values for genistein inhibition of protein tyrosine kinases, many reported experiments use genistein at concentrations where inhibition of protein histidine kinase occurs. It is possible that some of the observed effects of genistein in vivo may be due to inhibition of protein histidine kinase. PMID- 1639792 TI - Changes in rates of protein synthesis and eukaryotic initiation factor-4 inhibitory activity in cell-free translation systems of sea urchin eggs and early cleavage stage embryos. AB - The characteristics of cell-free translation systems prepared from unfertilized eggs and early cleavage stage embryos of the sea urchin, Strongylocentrotus purpuratus, closely reflect the developmentally regulated changes in protein synthesis initiation observed in vivo. Cell-free translation systems prepared over the first 0-6 h following fertilization show gradually increasing activities, mimicking the changes observed in vivo. The mechanisms underlying these increases are complex and occur at several levels. One factor contributing to the rise in protein synthetic rate is the gradual increase in eukaryotic initiation factor (eIF)-4 activity. This is correlated with the progressive inactivation of an inhibitor of eIF-4 function, which can be reactivated by in vitro manipulations. The relatively slow activation of eIF-4 follows similar kinetics to the increased utilization of maternal mRNA and ribosomes, in contrast to the rapid rise in maternal mRNA activation, and the increase in eIF-2B activity. This slow release from eIF-4 inhibition following a rapid release from eIF-2B inhibition and increased mRNA availability is reflected in the pattern of initiator tRNA binding to the small ribosomal subunit observed in cell-free translation systems. In translation systems from unfertilized eggs, initiator tRNA is unable to interact with the small ribosomal subunit, consistent with an initial block in both eIF-2B and eIF-4 activity. In translation systems from 30 min embryos, 48 S preinitiation complexes accumulate, reflecting the release from inhibition of mRNA availability and eIF-2B activity, but continued low activity of eIF-4. The accumulation of initiator tRNA in 48 S preinitiation complexes disappears gradually in translation systems from later embryos, as eIF-4 is slowly released from inhibition. PMID- 1639793 TI - Fusions of anthrax toxin lethal factor to the ADP-ribosylation domain of Pseudomonas exotoxin A are potent cytotoxins which are translocated to the cytosol of mammalian cells. AB - The lethal factor (LF) and edema factor (EF) components of anthrax toxin are toxic to animal cells only if internalized by interaction with the protective antigen (PA) component. PA binds to a cell surface receptor and is proteolytically cleaved to expose a binding site for LF and EF. To study how LF and EF are internalized and trafficked within cells, LF was fused to the translocation and ADP-ribosylation domains (domains II and III, respectively) of Pseudomonas exotoxin A. LF fusion proteins containing Pseudomonas exotoxin A domains II and III were less toxic than those containing only domain III. Fusion proteins with a functional endoplasmic reticulum retention sequence, REDLK, at the carboxyl terminus of domain III were less toxic than those with a nonfunctional sequence, LDER. The most potent fusion protein, FP33, had an EC50 = 2 pM on Chinese hamster ovary cells, exceeding that of native Pseudomonas exotoxin A (EC50 = 420 pM). Toxicity of all the fusion proteins required the presence of PA and was blocked by monensin. These data suggest that LF and LF fusion proteins are efficiently translocated from acidified endosomes directly to the cytosol without trafficking through other organelles, as is required for Pseudomonas exotoxin A. This system provides a potential vehicle for importing diverse proteins into the cytosol of mammalian cells. PMID- 1639794 TI - Chimeric L6 anti-tumor antibody. Genomic construction, expression, and characterization of the antigen binding site. AB - We report the cloning of the genomic variable region genes of the human carcinoma reactive murine monoclonal antibody L6 and their genetic linkage to human constant region exons to encode a human IgG1/kappa chimeric antibody. The chimeric protein was produced at levels greater than 20 micrograms/ml (enabling the initiation of clinical trials) and was found to have binding properties identical with that of the murine parent. The nucleic acid sequence of the variable regions was determined and found to be different than that previously reported (1). The deduced amino acid sequence was then used to generate a structural homology based three-dimensional model of the antibody binding site, which was found to share features with antibodies known to interact with a protein surface, but distinct from those that bind to carbohydrate epitopes. Biochemical analysis of binding between antibody and the in vitro-translated product of a cDNA clone that confers L6 immunoreactivity demonstrates that the antibody recognizes a protein epitope encoded by this transcript which requires the presence of membranes, but is unaffected by the removal of carbohydrate side chains. PMID- 1639796 TI - Function independence of microhelix aminoacylation from anticodon binding in a class I tRNA synthetase. AB - The monomeric form of the class I Escherichia coli methionine tRNA synthetase has a distinct carboxyl-terminal domain with a segment that interacts with the anticodon of methionine tRNA. This interaction is a major determinant of the specificity and efficiency of aminoacylation. The end of this carboxyl-terminal domain interacts with the amino-terminal Rossman fold that forms the site for amino acid activation. Thus, the carboxyl-terminal end may have evolved in part to integrate anticodon recognition with amino acid activation. We show here that internal deletions that disrupt the anticodon interaction have no effect on the kinetic parameters for amino acid activation. Moreover, an internally deleted enzyme can aminoacylate an RNA microhelix, which is based on the acceptor stem of methionine tRNA, with the same efficiency as the native protein. These results suggest that, in this enzyme, amino acid activation and acceptor helix aminoacylation are functionally integrated and are independent of the anticodon binding site. PMID- 1639795 TI - Sea urchin collagen evolutionarily homologous to vertebrate pro-alpha 2(I) collagen. AB - We isolated several overlapping cDNA clones covering the 4242 nucleotides of a Strongylocentrotus purpuratus transcript that codes for a fibrillar procollagen chain. The sea urchin polypeptide includes a 124-amino acid long amino pre propeptide, a 1064-amino acid alpha-chain inclusive of 338 uninterrupted Gly-X-Y repeats, and a 226-residue carboxyl-propeptide. The distribution of the highly conserved cysteines within the last domain together with the structural configuration of the amino-propeptide and the organization of the corresponding coding region, strongly suggest that the sea urchin gene is evolutionarily related to the vertebrate pro-alpha 2(I) collagen. This work, therefore, represents the first report of the complete primary structure of an invertebrate fibrillar procollagen chain. It also provides a new insight into the evolution of the amino-propeptide, the most divergent among the major protein domains of fibrillar procollagen chains. PMID- 1639797 TI - Fibrinogen binding to purified platelet glycoprotein IIb-IIIa (integrin alpha IIb beta 3) is modulated by lipids. AB - Soluble fibrinogen binding to the glycoprotein IIb-IIIa complex (integrin alpha IIb beta 3) requires platelet activation. The intracellular mediator(s) that convert glycoprotein IIb-IIIa into an active fibrinogen receptor have not been identified. Because the lipid composition of the platelet plasma membrane undergoes changes during activation, we investigated the effects of lipids on the fibrinogen binding properties of purified glycoprotein IIb-IIIa. Anion exchange chromatography of lipids extracted from platelets exposed to thrombin or other platelet agonists resolved an activity that increased fibrinogen binding to glycoprotein IIb-IIIa. A monoester phosphate was important for activity, and phosphatidic acid coeluted with the peak of activity. Purified phosphatidic acid dose-dependently promoted a specific interaction between glycoprotein IIb-IIIa and fibrinogen which possessed many but not all of the properties of fibrinogen binding to activated platelets. Phosphatidic acid appeared to increase the proportion of fibrinogen binding-competent glycoprotein IIb-IIIa complexes without altering their affinity for fibrinogen. The effects of phosphatidic acid were a result of specific structural properties of the lipid and were not mimicked by other phospholipids. Lysophosphatidic acid, however, was a potent inducer of fibrinogen binding to glycoprotein IIb-IIIa. These results demonstrate that specific lipids can affect fibrinogen binding to purified glycoprotein IIb IIIa and suggest that the lipid environment has the potential to influence fibrinogen binding to its receptor. PMID- 1639798 TI - Tocopherol analogs suppress arachidonic acid metabolism via phospholipase inhibition. AB - alpha-Tocopherol and three derivatives in which the phytol chain is modified or deleted were examined for their effect on cultured keratinocyte arachidonic acid metabolism. 2,2,5,7,8-Pentamethyl-6-hydroxychromane (PMC), in which the phytol chain is replaced by a methyl group, inhibited basal, bradykinin (BK)- and A23187 stimulated prostaglandin E2 (PGE2) synthesis with an apparent Ki of 1.3 microM. The Ki of the analogue with six carbon atoms in the side chain (C6) was 5 microM while that of the C11 analogue was 10 microM. No effect of alpha-tocopherol was observed. The mechanism of inhibition was studied using PMC. The effect of PMC on phospholipase and cyclooxygenase activity was assayed using stable isotope mass measurements of PGE2 formation, which assesses arachidonate release and cyclooxygenase metabolism simultaneously. BK-stimulated formation of PGE2, derived from endogenous phospholipid, was decreased 60% by 5 microM PMC and eliminated by 50 microM PMC, compared with controls. No difference in PGE2 formed from exogenous arachidonic acid was observed, indicating no effect of PMC on cyclooxygenase activity. In contrast, no effect of 5 microM PMC was observed on BK-stimulated [3H]arachidonic acid release from prelabeled cultures. The capacity of PMC to inhibit phospholipase activity in vitro was also assessed. PMC inhibited hydrolysis of phospholipid substrate by up to 60%. These results suggest that alpha-tocopherol analogues with alterations in the phytol chain inhibit eicosanoid synthesis by preferential inhibition of phospholipase. PMID- 1639799 TI - Translocation of protein kinase C isozymes in thrombin-stimulated human platelets. Correlation with 1,2-diacylglycerol levels. AB - Human platelets were found by immunoblot analysis to express protein kinase C (PKC) isozymes alpha, beta, delta, and zeta, but not gamma, epsilon, or eta. Exposure of platelets to thrombin, in the presence of 1 mM calcium, induced increased membrane association of PKC-alpha, -beta, and -zeta, while the subcellular distribution of PKC-delta remained unaltered. Maximal membrane association (2-fold) of PKC-alpha, -beta, and -zeta occurred within 1 min and was sustained for at least 10 min after the addition of thrombin. Similar results were obtained in the presence of the RGDS peptide, which blocks thrombin-induced binding of fibrinogen to its receptor, which indicates that PKC translocation was independent of fibrinogen binding. In the absence of added extracellular calcium, thrombin-induced translocation of PKC-alpha, -beta, and -zeta was transient, reaching a maximum at 1 min and returning to base line by 10 min. In the presence of calcium, thrombin induced a rapid (within 15 s) 8-fold rise in inositol 1,4,5 trisphosphate, which returned to baseline levels within 1 min, and a biphasic increase in sn-1,2-diacylglycerol (DAG), with peaks at 15 s and 2 min, which remained elevated for at least 5 min. Chelation of external calcium abolished the second phase of DAG formation but had no effect on the kinetics or magnitude of the increase in inositol 1,4,5-trisphosphate or the first phase of DAG formation. Two early PKC-dependent functions, serotonin release and 40-kDa protein phosphorylation, were independent of extracellular calcium and sustained DAG. These data demonstrate that in thrombin-stimulated human platelets the duration of the increased PKC membrane association closely parallels that of increased DAG content, and sustained elevations in DAG content and PKC translocation are dependent on extracellular calcium. PMID- 1639800 TI - Photoaffinity labeling of T4 endonuclease V with a substrate containing a phenyldiazirine derivative. AB - T4 endonuclease V recognizes thymine photodimers in DNA duplexes and, in a two step reaction, cleaves the glycosyl linkage of the 5'-side thymidine and the phosphodiester linkage. To determine the amino acid residues responsible for binding thymine photodimers, a photoaffinity reagent, 4-(1-azi-2,2,2 trifluoroethyl)-benzoate, was linked to the aminoalkylphosphonate of a thymine photodimer in a 14-mer duplex. The reactive substrate was treated with the enzyme under UV light (365 nm). The nascent enzyme and the modified enzyme were treated with lysyl endopeptidase, and the peptide maps were compared. Three peptides from the C terminus were found to interact with the reactive oligonucleotide to various extents. The three modified peptides were isolated and analyzed by Edman degradation. The amino acid residues Gly-133, Tyr-129, and Thr-89 were partially linked with the reactive substrate and may be involved in the binding of thymine photodimers. PMID- 1639801 TI - V(D)J recombination on minichromosomes is not affected by transcription. AB - It has been shown previously by others that transcription is temporally correlated with the onset of V(D)J recombination at the endogenous antigen receptor loci. We have been interested in determining whether this temporal correlation indicates a causal connection between these two processes. We have compared V(D)J recombination minichromosome substrates that have transcripts running through the recombination zone with substrates that do not in a transient transfection assay. In this system, the substrates acquire a minichromosome conformation within the first several hours after transfection. We find that the substrates recombine equally well over a 100-fold range in transcriptional variation. In additional studies, we have taken substrates that have low levels of transcription and inhibited transcription further by methylating the substrate DNA or by treating the cells with a general transcription inhibitor (alpha amanitin). Although these treatments decrease the level of expression an additional 10-100-fold, there is still no observable effect on V(D)J recombination. Based on these results, we conclude that transcription is not necessary for the V(D)J reaction mechanism and does not alter substrate structure at the DNA level or at the simplest levels of chromatin structure in a way that affects the reaction. PMID- 1639802 TI - Characterization of the charged components and their topology on the surface of plant seed oil bodies. AB - Oil bodies of plant seeds contain a triacylglycerol matrix surrounded by a monolayer of phospholipids embedded with alkaline proteins called oleosins. Oil bodies isolated from maize (Zea mays L.) in a medium of pH 7.2 maintained their entities but aggregated when the pH was lowered to 6.8 and 6.2. Aggregation did not lead to coalescence and was reversible with an elevation of the pH. Further decrease of the pH from 6.2 to 5.0 retarded the aggregation. Aggregation at pH 7.2 was induced with 2 mM CaCl2 or MgCl2 but not with NaCl. Aggregation at pH 6.8 was prevented by 10 microM sodium dodecyl sulfate but not with NaCl. We conclude that oil bodies have a negatively charged surface at pH 7.2 and an isoelectric point of about 6.0. This conclusion is supported by isoelectrofocusing results and by theoretical calculation of the positive charges in the oleosins and the negative charges in phosphatidylserine, phosphatidylinositol, and free fatty acids. Apparently, lowering of the pH from 7.2 to 6.2 protonates the histidine residues in the oleosins, and neutralizes the oil bodies. Further decrease of the pH to 5.0 likely protonates the free fatty acids and produces positively charged organelles. Similar charge properties were observed in the oil bodies isolated from rape, flax, and sesame seeds. An analysis of the oleosin secondary structures reveals an N-terminal amphipathic domain, a central hydrophobic anti parallel beta-strand domain (not found in any other known protein), and a C terminal amphipathic alpha-helical domain. In the two amphipathic domains, the positively charged residues are orientated toward the interior facing the negative charged lipids, whereas the negatively charged residues are exposed to the exterior. The negatively charged surface is a major factor in maintaining the oil bodies as stable individual entities. PMID- 1639803 TI - Subunit structure of cell-specific E box-binding proteins analyzed by quantitation of electrophoretic mobility shift. AB - Expression of insulin and immunoglobulin genes is dependent on the presence of E boxes (consensus sequence CAXXTG) within the enhancer regions. These sequences are recognized by cell-specific nuclear factors IEF1 (insulin enhancer factor 1) and LEF1 (lymphoid enhancer factor 1). Although IEF1 and LEF1 are distinct by several parameters, they are both recognized by antisera to the mouse helix-loop helix (HLH) protein A1 (a homolog of the human protein E47, product of the E2A gene). This suggests that A1/E47 or a close relative is a component of both complexes. In order to further characterize the complexes, we have used in vitro translated DNA-binding proteins of known size to verify that electrophoretic mobility shift analysis can be used to estimate the molecular weight of DNA binding proteins from both the HLH family and the leucine zipper family. Under the conditions used, migration is relatively insensitive to changes in protein charge. This analysis, in combination with mixing experiments between nuclear extracts and in vitro translated HLH proteins, indicates that IEF1 and LEF1 are dimeric complexes. IEF1 behaves as a complex of two proteins, one of which is 67 kDa and is recognized by antibodies to A1, and the second of which is 25 kDa. LEF1 on the other hand, appears to be a complex of two proteins of 67 kDa. The size of the 67-kDa subunits is consistent with that reported for the full-length E2A gene products. The 25-kDa subunit of IEF1 forms DNA-binding heterodimers with A1 but not MyoD and is present in a limited range of cell types, features characteristic of class B HLH proteins such as MyoD and achaete-scute. Taken together, the data support the idea that the E2A gene products are involved directly in regulation of insulin and immunoglobulin gene expression; regulation of the insulin gene apparently requires, in addition, the 25-kDa HLH protein (designated IESF1 for insulin enhancer-specific factor 1). PMID- 1639804 TI - Oleate-mediated stimulation of apolipoprotein B secretion from rat hepatoma cells. A function of the ability of apolipoprotein B to direct lipoprotein assembly and escape presecretory degradation. AB - Physiological concentrations of oleate stimulate apolipoprotein (apo) B containing lipoprotein secretion from HepG2 cells without increasing apoB mRNA levels. The purpose of this study was to determine whether oleate acts by increasing translation of apoB mRNA or through posttranslational effects on the apoB protein. To address the mechanism of oleate-stimulated secretion of apoB, a series of carboxyl terminally truncated apoB constructs was made. Each contained the SV40 early promoter, the apoB 5'-untranslated region, and SV40 polyadenylation signals. Any difference in the response to oleate between endogenous apoB and the proteins encoded by the constructs or between the constructs themselves should thus depend on the protein sequence. Stable transformants were established for each of the constructs in the rat hepatoma cell line McArdle-RH7777. The effect of oleate on secretion of the apoB protein products was determined by labeling with [35S]methionine, immunoprecipitation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Carboxyl-terminal truncation of apoB41 resulted in a loss of the ability of apoB secretion to respond to oleate. Ultracentrifugation of secreted proteins on continuous CsCl gradients from 1.0-1.4 g/ml revealed that this correlated with a decrease in the ability of apoB to be recovered as a buoyant lipoprotein particle. Addition of oleate decreased the densities at which the short forms of apoB secreted as lipoproteins were recovered. Pulse-chase analysis of the secretion of apoB100 and of the truncated proteins revealed that they all underwent rapid posttranslational intracellular degradation. We conclude that oleate has no effect on the translation of apoB mRNA but promotes the secretion of apoB containing lipoproteins by reducing presecretory degradation of those forms of apoB that can produce buoyant lipoproteins. PMID- 1639805 TI - Identification of mitochondrial branched chain aminotransferase and its isoforms in rat tissues. AB - The tissue distribution and subcellular location of branched chain aminotransferase was analyzed using polyclonal antibodies against the enzyme purified from rat heart mitochondria (BCATm). Immunoreactive proteins were visualized by immunoblotting. The antiserum recognized a 41-kDa protein in the 100,000 x g supernatant from a rat heart mitochondrial sonicate. The 41-kDa protein was always present in mitochondria which contained branched chain aminotransferase activity, skeletal muscle, kidney, stomach, and brain, but not in cytosolic fractions. In liver mitochondria, which have very low levels of branched chain aminotransferase activity, the 41-kDa protein was not present. However, two immunoreactive proteins of slightly higher molecular masses were identified. These proteins were located in hepatocytes. The 41-kDa protein was present in fetal liver mitochondria but not in liver mitochondria from 5-day neonates. Thus disappearance of the 41-kDa protein coincided with the developmental decline in liver branched chain aminotransferase activity. Two dimensional immunoblots of isolated BCATm immunocomplexes showed that the liver immunoreactive proteins were clearly different from the heart and kidney proteins which exhibited identical immunoblots. Investigation of BCATm in subcellular fractions prepared from different skeletal muscle fiber types revealed that branched chain aminotransferase is exclusively a mitochondrial enzyme in skeletal muscles. Although total detergent-extractable branched chain aminotransferase activity was largely independent of fiber type, branched chain aminotransferase activity and BCATm protein concentration were highest in mitochondria prepared from white gastrocnemius followed by mixed skeletal muscles with lowest activity and protein concentration found in soleus mitochondria. These quantitative differences in mitochondrial branched chain aminotransferase activity and enzyme protein content suggest there may be differential expression of BCATm in different muscle fiber types. PMID- 1639806 TI - Histamine N-methyltransferase from rat kidney. Cloning, nucleotide sequence, and expression in Escherichia coli cells. AB - Complementary DNA clones encoding rat kidney histamine N-methyltransferase have been isolated using synthetic oligonucleotide probes based on partial amino acid sequences of tryptic peptides of the purified enzyme. The 1.3-kilobase cDNA consisted of a 5'-noncoding region of 8 nucleotides, a coding region of 885 nucleotides, and a 3'-noncoding region of 369 nucleotides. The encoded protein of 295 amino acid residues had a calculated molecular weight of 33,940.2. After introduction of a prokaryotic expression vector containing the isolated cDNA, Escherichia coli cells expressed histamine N-methyltransferase activity. The enzyme expressed in these cells was isolated and purified as a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, whose mobility was identical to the natural enzyme purified from rat kidney. The recombinant enzyme had Vmax and Km values for both histamine and S-adenosylmethionine identical to those of the natural enzyme. All of the inhibitors of the natural enzyme tested showed similar Ki values on both recombinant and natural enzyme. PMID- 1639807 TI - Biologically important interactions between synthetic peptides of the N-terminal region of troponin I and troponin C. AB - The interaction between troponin I and troponin C plays a critical role in the regulation of muscle contraction. In this study the interaction between troponin C (TnC) and the N-terminal region of TnI was investigated by the synthesis of three TnI peptides (residues 1-40/Rp, 10-40, and 20-40). The regulatory peptide (Rp) on binding to TnC prevents the ability of TnC to release the inhibition of the acto-S1-tropomyosin ATPase activity caused by TnI or the TnI inhibitory peptide (Ip), residues 104-115. A stable complex between TnC and Rp in the presence of Ca2+ was demonstrated by polyacrylamide gel electrophoresis in the presence of 6 M urea. Rp was able to displace TnI from a preformed TnI.TnC complex. In the absence of Ca2+, Rp was unable to maintain a complex with TnC in benign conditions of polyacrylamide gel electrophoresis which demonstrates the Ca(2+)-dependent nature of this interaction. Size-exclusion chromatography demonstrated that the TnC.Rp complex consisted of a 1:1 complex. The results of these studies have shown that the N-terminal region of TnI (1-40) plays a critical role in modulating the Ca(2+)-sensitive release of TnI inhibition by TnC. PMID- 1639808 TI - Microtubule-associated protein tau is phosphorylated by protein kinase C on its tubulin binding domain. AB - We have analyzed the in vitro phosphorylation of tau protein by Ca2+/calmodulin dependent protein kinase, casein kinase II, and proline-directed serine/threonine protein kinase. These kinases phosphorylate tau protein in sites localized in different regions of the molecule, as determined by peptide mapping analyses. Focusing on the phosphorylation of tau by protein kinase C, it was calculated as an incorporation of 4 mol of phosphate/mol of tau. Limited proteolysis assays suggest that the phosphorylation sites could be located within the tubulin binding domain. Direct phosphorylation of synthetic peptides corresponding to the cysteine-containing tubulin-binding region present in both fetal and adult tau isoforms demonstrates that serine 313 is modified by protein kinase C. Phosphorylation of the synthetic peptide by protein kinase C diminishes its binding to tubulin, as compared with the unphosphorylated peptide. PMID- 1639809 TI - Regulated expression of syndecan in vascular smooth muscle cells and cloning of rat syndecan core protein cDNA. AB - cDNA encoding the core protein of rat syndecan was cloned from a neonatal rat aortic cDNA library by polymerase chain reaction amplification. Expression of syndecan mRNA in rat aortic vascular smooth muscle (VSM) cells was demonstrated by reverse transcriptase-linked polymerase chain reaction amplification of syndecan sequences using total RNA from rat aortic VSM cells as templates. Polyclonal antibodies against rat syndecan core protein were produced by immunizing rabbits with a recombinant fusion protein containing a fragment of the extracellular domain. The anti-syndecan antibodies immunoprecipitated a large 35SO4-labeled molecule synthesized by cultured rat aortic VSM cells. The immunoprecipitated molecule was identified as a hybrid proteoglycan, based on results of alkaline, nitrous acid, and chondroitinase ABC digestions. On immunoblots the antibodies recognized a proteoglycan of greater than 200 kDa, with a core protein size after deglycosylation of approximately 50 kDa. The anti syndecan antibodies stained cultured rat aortic VSM cells as well as tissue sections of neonatal and adult rat aortas in the medial, smooth muscle layer. On Northern blots of RNA isolated from cultured VSM cells, a syndecan cDNA probe hybridized to a major RNA species of 2.6 kilobases. Quantitative Northern blot analysis of total RNA isolated from VSM cells harvested at different cell densities revealed a decrease in syndecan mRNA levels with increased cell density. These results demonstrate the regulated synthesis of syndecan by rat VSM cells. PMID- 1639810 TI - The bimB3 mutation of Aspergillus nidulans uncouples DNA replication from the completion of mitosis. AB - A conditionally lethal mutation in the bimB gene of Aspergillus nidulans disrupts the normal regulatory patterns associated with mitotic events. This results in DNA replication in the absence of the completion of mitosis in the mutant at restrictive temperature. This defect yields large polyploid nuclei after several hours at restrictive temperature. The bimB gene has been cloned by genetic mapping and chromosome walking from the previously cloned amdS gene. The cloned DNA complements the temperature-sensitive recessive bimB3 mutation. Sequence analysis of overlapping complementary DNA clones for bimB predicts a polypeptide of 2,068 amino acids. The predicted polypeptide of 227,958 Da is shown to have a carboxyl-terminal region similar to those of the budding yeast ESP1 and fission yeast cut1+ genes. In contrast these genes exhibit no other regions of similarity to one another. The conserved domain in these three proteins and the similarity of the terminal mutant phenotypes for these genes are suggestive of a conserved function for this domain in each of the predicted polypeptides. We also present evidence for a second gene in the genome of A. nidulans which also has this conserved carboxyl-terminal region, suggesting that bimB, ESP1, and cut1+ may be members of a small gene family. PMID- 1639811 TI - Hormone- and substrate-regulated intracellular degradation of cytochrome P450 (2E1) involving MgATP-activated rapid proteolysis in the endoplasmic reticulum membranes. AB - We have examined differences in post-translational regulation between rat liver ethanol-inducible cytochrome P450 2E1 (CYP2E1) and phenobarbital-inducible CYP2B1 using hepatocyte cultures and subcellular fractions, prepared from starved and acetone-treated rats. The intracellular degradation of CYP2E1 was rapid (approximate t1/2 = 9 h) and increased by glucagon treatment of the cells in an isozyme-specific manner, whereas CYP2B1 degradation in the same cells, was slower (t1/2 = 21 h). The glucagon effect on CYP2E1 degradation was abolished by either cycloheximide treatment of cells, indicating the involvement of protein components with rapid turnover, or by lowering of the culture temperature to 23 degrees C. The rapid phase of CYP2E1 degradation was not influenced by inhibitors of the autophagosomal/lysosomal pathway. In vitro experiments with isolated liver microsomes revealed the presence of a Mg(2+)-ATP-activated proteolytic system active on CYP2E1, previously modified by phosphorylation on Ser-129 or denatured by reactive metabolites formed from carbon tetrachloride. Imidazole, a CYP2E1 substrate, specifically inhibited the rapid intracellular degradation of CYP2E1 and also prevented phosphorylation and subsequent proteolysis in isolated microsomes. In contrast, no proteolysis of CYP2B1 occurred under the conditions used. The microsomal Mg(2+)-ATP-dependent CYP2E1 proteolysis could not be solubilized with high salt and 0.05% sodium cholate, indicating the action of membrane-integrated protease(s). Subfractionation of microsomes revealed that the Mg(2+)-ATP-dependent proteolytic system active on CYP2E1 was present in both rough and smooth endoplasmic reticulum. It is suggested that hepatic cytochromes P450 are degraded both in a bulk process, according to the autophagosomal/lysosomal pathway and more rapidly, in a hormone- and substrate regulated fashion, by a specific proteolytic system in the endoplasmic reticulum, active on physiologically or exogenously modified molecules. PMID- 1639812 TI - Agonist-induced changes in the structure of the acetylcholine receptor M2 regions revealed by photoincorporation of an uncharged nicotinic noncompetitive antagonist. AB - To characterize structural changes induced in the nicotinic acetylcholine receptor (AChR) by agonists, we have mapped the sites of photoincorporation of the cholinergic noncompetitive antagonist 3-(trifluoromethyl)-3-(m [125I]iodophenyl)diazirine (]125I]TID) in the presence and absence of 50 microM carbamylcholine. [125I]TID binds to the AChR with similar affinity under both these conditions, but agonist inhibits photoincorporation into all subunits by greater than 75% (White, B. H., Howard, S., Cohen, S. G., and Cohen, J. B. (1991) J. Biol. Chem. 266, 21595-21607). [125I]TID-labeled sites on the beta- and delta subunits were identified by amino-terminal sequencing of both cyanogen bromide (CNBr) and tryptic fragments purified by Tricine sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by reversed-phase high-performance liquid chromatography. In the absence of agonist, [125I]TID specifically labels homologous aliphatic residues (beta L-257, delta L-265, beta V-261, and delta V 269) in the M2 region of both subunits. In the presence of agonist, labeling of these residues is reduced approximately 90%, and the distribution of labeled residues is broadened to include a homologous set of serine residues at the amino terminus of M2. In the beta-subunit residues beta S-250, beta S-254, beta L-257, and beta V-261 are all labeled in the presence of carbamylcholine. This pattern of labeling supports an alpha-helical model for M2 with the labeled face forming the ion channel lumen. The observed redistribution of label in the resting and desensitized states provides the first direct evidence for an agonist-dependent rearrangement of the M2 helices. The efficient labeling of the resting state channel in a region capable of structural change also suggests a plausible model for AChR gating in which the aliphatic residues labeled by [125I]TID form a permeability barrier to the passage of ions. We also report increased labeling of the M1 region of the delta-subunit in the presence of agonist. PMID- 1639813 TI - In vitro specificity of EcoRI DNA methyltransferase. AB - The sequence selectivity of enzyme-DNA interactions was analyzed by comparing discrimination between synthetic oligonucleotides containing the canonical site GAATTC and altered DNA sequences with the EcoRI DNA methyltransferase. The specificities (kcat/KmDNA) are decreased from 5- to 23,000-fold relative to the unmodified site. For several substrates the decrease in kcat makes a disproportionate contribution to the specificity difference, suggesting that discrimination is mediated by the placement of critical catalytic residues rather than binding interactions. This is supported by our observation that specificity changes are generally not followed by changes in the stability of the methyltransferase-DNA complexes. Also, base pair substitutions near the site of methylation result in greater decreases in complex stability, suggesting that recognition and catalytic mechanisms overlap. PMID- 1639814 TI - Purification and characterization of indolepyruvate decarboxylase. A novel enzyme for indole-3-acetic acid biosynthesis in Enterobacter cloacae. AB - Indolepyruvate decarboxylase, a key enzyme for indole-3-acetic acid biosynthesis, was found in extracts of Enterobacter cloacae. The enzyme catalyzes the decarboxylation of indole-3-pyruvic acid to yield indole-3-acetaldehyde and carbon dioxide. The enzyme was purified to apparent homogeneity from Escherichia coli cells harboring the genetic locus for this enzyme obtained from E. cloacae. The results of gel filtration experiments showed that indolepyruvate decarboxylase is a tetramer with an M(r) of 240,000. In the absence of thiamine pyrophosphate and Mg2+, the active tetramers dissociate into inactive monomers and dimers. However, the addition of thiamine pyrophosphate and Mg2+ to the inactive monomers and dimers results in the formation of active tetramers. These results indicate that the thiamine pyrophosphate-Mg2+ complex functions in the formation of the tetramer, which is the enzymatically active holoenzyme. The enzyme exhibited decarboxylase activity with indole-3-pyruvic acid and pyruvic acid as substrates, but no decarboxylase activity was apparent with L-tryptophan, indole-3-lactic acid, beta-phenylpyruvic acid, oxalic acid, oxaloacetic acid, and acetoacetic acid. The Km values for indole-3-pyruvic acid and pyruvic acid were 15 microM and 2.5 mM, respectively. These results indicate that indole-3-acetic acid biosynthesis in E. cloacae is mediated by indolepyruvate decarboxylase, which has a high specificity and affinity for indole-3-pyruvic acid. PMID- 1639815 TI - Transcriptional regulation of human apolipoprotein genes ApoB, ApoCIII, and ApoAII by members of the steroid hormone receptor superfamily HNF-4, ARP-1, EAR 2, and EAR-3. AB - Apolipoproteins B, CIII, and AII are synthesized primarily in the liver and intestine and play an important role in lipid and cholesterol metabolism. It was previously shown that the cis-acting elements (BA1 (-79 to -63), CIIIB (-87 to 63), and AIIJ (-740 to -719) present in the regulatory regions of the human apoB, apoCIII, and apoAII genes, respectively, are recognized by common transcription factors present in hepatic nuclear extracts. This report shows that four members of the steroid receptor superfamily, ARP-1, EAR-2, EAR-3, and HNF-4, bind specifically to the regulatory elements BA1, CIIIB, and AIIJ. Dissociation constant measurements showed that ARP-1, EAR-2, and HNF-4 bind to elements BA1 and CIIIB with similar affinities (Kd 1-3 nM). Cotransfection experiments in HepG2 cells revealed that ARP-1, EAR-2, and EAR-3 repressed the BA1, CIIIB, and AIIJ element-dependent transcription of the reporter gene constructs and the transcription driven by homopolymeric promoters containing either five BA1 or two CIIIB elements. In contrast, HNF-4 activated transcription of reporter genes containing the elements BA1, CIIIB, and AIIJ and reversed the ARP-1-mediated repression of the apoB and apoCIII genes. These results suggested that the opposing transcription effects observed between HNF-4 and ARP-1 may be due to competition for binding to the same regulatory element. Mutations which affected the binding of HNF-4 to elements BA1 and CIIIB affected its ability to activate transcription of the apoB and apoCIII reporter genes, respectively. Transcriptional activation by HNF-4 depended on the presence of elements II (-112 to -94) and III (-86 to -62) of the apoB and H (-705 to -690), I (-766 to -726), and J (-792 to -779) of the apoCIII promoters, indicating that transcriptional activation of apoB and apoCIII genes by HNF-4 requires the synergistic interaction of factors binding to these elements. The finding that HNF-4, ARP-1, EAR-2 and EAR-3 can regulate the expression of the apoB, apoCIII, and apoAII genes suggest that these nuclear hormone receptors may be an important part of the signal transduction pathways modulating lipid metabolism and cholesterol homeostasis. PMID- 1639816 TI - Specificity of phosphatidylserine-containing membrane binding sites for factor VIII. Studies with model membranes supported by glass microspheres (lipospheres). AB - Factor VIII functions in an enzyme complex upon the activated platelet membrane where phosphatidylserine exposure correlates with expression of receptors for factor VIII. To evaluate the specificity of phosphatidylserine-containing membrane binding sites for factor VIII, we have developed a novel membrane model in which phospholipid bilayers are supported by glass microspheres (lipospheres). The binding of fluorescein-labeled factor VIII to lipospheres with membranes of 15% phosphatidylserine was equivalent to binding to phospholipid vesicles (KD = 4.8 nM). Purified von Willebrand factor (vWf), a carrier protein for factor VIII, decreased membrane binding of factor VIII with a Ki of 10 micrograms/ml. Likewise, normal plasma decreased bound factor VIII by more than 90% whereas plasma lacking vWf decreased the binding of factor VIII by only 20%. Proteolytic activation of factor VIII by thrombin, which releases factor VIII from vWf, increased liposphere binding in the presence of vWf and in the presence of normal plasma. Although factor V is homologous to factor VIII and binds to lipospheres with the same affinity, purified factor V was not an efficient competitor for the membrane binding sites of factor VIII. These results indicate that phosphatidylserine-containing membrane sites have sufficient specificity to select thrombin-activated factor VIII from the range of phospholipid-binding proteins in plasma. PMID- 1639817 TI - A family of bacterial regulators homologous to Gal and Lac repressors. AB - We describe a family of proteins which regulate transcription of inducible genes in bacteria (GalR-LacI family). An alignment of the proteins in the GalR-LacI family is presented in which these proteins show a very high degree of similarity (60%) throughout the entire sequences. The homology is greatest among the amino terminal DNA binding domains. Since a portion of the operator sequences occupied by these proteins is also conserved, a similar DNA structure may be required for specific recognition of DNA by members of the GalR-LacI family. Highly conserved motifs involved in effector binding and oligomerization are also identified. This compilation suggests a widespread conservation of these regulators among bacteria, and have strong implications for further study of peptide motifs in domain function, as well as pathways of protein evolution. PMID- 1639818 TI - Inhibition of the relative movement of actin and myosin by caldesmon and calponin. AB - Contractile activity of myosin II in smooth muscle and non-muscle cells requires phosphorylation of myosin by myosin light chain kinase. In addition, these cells have the potential for regulation at the thin filament level by caldesmon and calponin, both of which bind calmodulin. We have investigated this regulation using in vitro motility assays. Caldesmon completely inhibited the movement of actin filaments by either phosphorylated smooth muscle myosin or rabbit skeletal muscle heavy meromyosin. The amount of caldesmon required for inhibition was decreased when tropomyosin is present. Similarly, calponin binding to actin resulted in inhibition of actin filament movement by both smooth muscle myosin and skeletal muscle heavy meromyosin. Tropomyosin had no effect on the amount of calponin needed for inhibition. High concentrations of calmodulin (10 microM) in the presence of calcium completely reversed the inhibition. The nature of the inhibition by the two proteins was markedly different. Increasing caldesmon concentrations resulted in graded inhibition of the movement of actin filaments until complete inhibition of movement was obtained. Calponin inhibited actin sliding in a more "all or none" fashion. As the calponin concentration was increased the number of actin filaments moving was markedly decreased, but the velocity of movement remained near control values. PMID- 1639820 TI - Conjugation of soluble CD4 without loss of biological activity via a novel carbohydrate-directed cross-linking reagent. AB - Chemical conjugates of recombinant soluble CD4 (sCD4) with toxins, or with antibodies that activate cytotoxic T cells, can be used to direct selective killing of human immunodeficiency virus (HIV)-infected cells. This approach takes advantage of the ability of sCD4 to bind with high affinity to gp120, the envelope protein of HIV-1, which is expressed on actively infected cells. However, conjugation of sCD4 via reagents that target amino groups may reduce its affinity for gp120, since at least one such group is important for gp120 binding. Here, we describe a novel cross-linking reagent which enables the conjugation of sCD4 via its carbohydrate moieties rather than its free amino groups. This heterobifunctional reagent, 4-(4-N-maleimidophenyl)butyric acid hydrazide (MPBH), combines a nucleophilic hydrazide with an electrophilic maleimide, thereby allowing coupling of carbohydrate-derived aldehydes to free thiols. We describe conditions by which MPBH is coupled selectively to the sialic acid residues of sCD4, and exemplify the use of MPBH by conjugating sCD4 to hemoglobin and to beta galactosidase. We show that, whereas conjugation of sCD4 via amino groups markedly reduces its gp120 binding affinity, conjugation via the carbohydrate chains using MPBH does not affect binding. Moreover, we demonstrate the ability of a sCD4-MPBH-fluorescein conjugate to label HIV-infected human CEM cells selectively. These results indicate that, by targeting its carbohydrate moieties, sCD4 can be cross-linked to other molecules without compromising its function. The approach described here can be useful for glycoproteins in which amino groups, but not carbohydrates, are important for function. More generally, this approach can be considered for use in cross-linking glycoconjugates to compounds which either contain thiols, or to which thiols can be added. PMID- 1639819 TI - Deficiencies in sex-regulated expression and levels of two hepatic sterol carrier proteins in a murine model of Niemann-Pick type C disease. AB - Hepatic sterol carrier protein-2 (SCP2) and sterol carrier protein-X (SCPx) levels in normal and in mutant Niemann-Pick Type C mice were determined by immunoblotting with antiserum against rat SCP2. A 14-kDa protein (SCP2) was detected in the cytosol fraction and a 58-kDa protein (SCPx) was found in both cytosolic and organellar fractions. Expression of hepatic SCPx protein was developmentally regulated in a sex-specific pattern. The amounts of organelle associated SCPx increased 4-fold during sexual development of normal males but decreased dramatically during development of normal females. Levels of hepatic SCP2 increased much less dramatically during sexual maturation of normal males and females. Adult Niemann-Pick Type C mice were deficient in both hepatic SCPx and SCP2. The deficit in SCPx in affected males reflected a failure to increase hepatic SCPx levels during sexual maturation. In affected males SCPx remained at levels found in immature mice. Affected male and female mice were also unable to maintain levels of hepatic SCP2. The level of SCP2 was near normal in affected immature males and subnormal in affected immature females. During sexual maturation hepatic SCP2 declined in affected animals. PMID- 1639821 TI - In vivo expression and stoichiometric sulfation of the artificial protein sulfophilin, a polymer of tyrosine sulfation sites. AB - To gain insight into the structural requirements for tyrosine sulfation in vivo, we have constructed and expressed an artificial gene encoding a polypeptide substrate for tyrosylprotein sulfotransferase. This gene codes for a protein, referred to as sulfophilin, which consists of a 12-times repeated heptapeptide unit corresponding to the identified tyrosine sulfation site of chromogranin B (secretogranin I), Glu-Glu-Pro-Glu-Tyr-Gly-Glu. The gene was fused to the signal sequence of secretogranin II to direct the sulfophilin protein to the secretory pathway. Stable expression of the artificial gene in NIH 3T3 cells resulted in the secretion of sulfated sulfophilin. Analysis of the stoichiometry of sulfation revealed that each of the 12 tyrosyl residues in sulfophilin was sulfated. Remarkably, up to 50% of the total protein-bound tyrosine sulfate secreted by the cells was contained in sulfophilin. The results indicate that the structural information contained in the heptapeptide motif is sufficient for stoichiometric tyrosine sulfation to occur in the living cell. PMID- 1639822 TI - Mapping of the functional domains in the amino-terminal region of calponin. AB - Three chymotryptic fragments accounting for almost the entire amino acid sequence of gizzard calponin (Takahashi, K., and Nadal-Ginard, B. (1991) J. Biol. Chem. 266, 13284-13288) were isolated and characterized. They encompass the segments of residues 7-144 (NH2-terminal 13-kDa peptide), 7-182 (NH2-terminal 22-kDa peptide), and 183-292 (COOH-terminal 13-kDa peptide). They arise from the sequential hydrolysis of the peptide bonds at Tyr182-Gly183 and Tyr144-Ala145 which were protected by the binding of F-actin to calponin. Only the NH2-terminal 13- and 22-kDa fragments were retained by immobilized Ca(2+)-calmodulin, but only the larger 22 kDa entity cosedimented with F-actin and inhibited, in the absence of Ca(2+)-calmodulin, the skeletal actomyosin subfragment-1 ATPase activity as the intact calponin. Since the latter peptide differs from the NH2-terminal 13 kDa fragment by a COOH-terminal 38-residue extension, this difference segment appears to contain the actin-binding domain of calponin. Zero-length cross-linked complexes of F-actin and either calponin or its 22-kDa peptide were produced. The total CNBr digest of the F-actin-calponin conjugate was fractionated over immobilized calmodulin. The EGTA-eluted pair of cross-linked actin-calponin peptides was composed of the COOH-terminal actin segment of residues 326-355 joined to the NH2-terminal calponin region of residues 52-168 which seems to contain the major determinants for F-actin and Ca(2+)-calmodulin binding. PMID- 1639823 TI - The soybean vegetative storage proteins VSP alpha and VSP beta are acid phosphatases active on polyphosphates. AB - The soybean vegetative storage protein genes (vspA, and vspB) are regulated in a complex manner developmentally and in response to external stimuli such as wounding and water deficit. The proteins accumulate to almost one-half the amount of soluble leaf protein when soybean plants are continually depodded and have been identified as storage proteins because of their abundance and pattern of expression in plant tissues. We have shown that purified VSP homodimers (VSP alpha and VSP beta) and heterodimers (VSP alpha/beta) possess acid phosphatase activity (alpha = 0.3-0.4 units/mg; beta = 2-4 units/mg; alpha/beta = 7-10 units/mg). Specific activities were determined by monitoring o-carboxyphenyl phosphate (0.7 mM) cleavage at pH 5.5 (VSP alpha) or pH 5.0 (VSP alpha/beta and VSP beta) in 0.15 M sodium acetate buffer at 25 degrees C. These enzymes are active over a broad pH range, maintaining greater than 40% of maximal activity from pH 4.0 to 6.5 and having maximal activity at pH 5.0-5.5. They are inactivated by sodium fluoride, sodium molybdate, and heating at 70 degrees C for 10 min. These phosphatases can liberate Pi from several different substrates, including napthyl acid phosphate, carboxyphenyl phosphate, sugar-phosphates, glyceraldehyde 3-phosphate, dihydroxyacetone phosphate, phosphoenolpyruvate, ATP, ADP, PPi, and short chain polyphosphates. VSP alpha/beta cleaved phosphoenolpyruvate, ATP, ADP, PPi, and polyphosphates most efficiently. Apparent Km and Vmax values at 25 degrees C and pH 5.0 were 42 microM and 2.0 mumol/min/mg, 150 microM and 4.2 mumol/min/mg, and 420 microM and 4.1 mumol/min/mg, for tetrapolyphosphate, pyrophosphate, and phosphoenolpyruvate, respectively. PMID- 1639824 TI - Rat procathepsin B. Proteolytic processing to the mature form in vitro. AB - Expression of rat procathepsin B in yeast led to the secretion of both the latent and mature forms of the enzyme. Culture in the presence of a cysteine proteinase inhibitor prevented this processing. We have expressed and purified a mutant form of rat procathepsin B whose active-site cysteine residue has been changed to a serine, and which also lacks the glycosylation site in the mature region of the protein. This non-active mutant protein was secreted essentially in an unprocessed form. The purified protein has been incubated with a variety of proteinases, and results indicate that cathepsins D and L, as well as mature cathepsin B itself, can produce a processed (single-chain) form of cathepsin B from this precursor. Amino-terminal sequencing of these processed forms has revealed that they are all elongated by a few residues with respect to the mature form found in vivo. The action of a combination of cathepsin B with dipeptidylpeptidase I produced a single-chain form of cathepsin B with the correct amino terminus. This work has also shown that the processing of procathepsin B to a single-chain form can be an autocatalytic process, in at least an intermolecular manner. PMID- 1639825 TI - Expression of TTK, a novel human protein kinase, is associated with cell proliferation. AB - We have isolated the full-length sequence for a unique human kinase, designated TTK. TTK was initially identified by screening of a T cell expression library with anti-phosphotyrosine antibodies. The kinases most closely related to TTK are the SPK1 serine, threonine and tyrosine kinase, the Pim1, PBS2, and CDC2 serine/threonine kinases, and the TIK kinase which was also identified through screening of an expression library with anti-phosphotyrosine antibodies. However, the relationships are distant with less than 25% identity. Nevertheless, TTK is highly conserved throughout phylogeny with hybridizing sequences being detected in mammals, fish, and yeast. TTK mRNA is present at relatively high levels in testis and thymus, tissues which contain a large number of proliferating cells, but is not detected in most other benign tissues. Freshly isolated cells from most malignant tumors assessed expressed TTK mRNA. As well, all rapidly proliferating cell lines tested expressed TTK mRNA. Escherichia coli expressing the complete kinase domain of TTK contain markedly elevated levels of phosphoserine and phosphothreonine as well as slightly increased levels of phosphotyrosine. Taken together, these findings suggest that expression of TTK, a previously unidentified member of the family of kinases which can phosphorylate serine, threonine, and tyrosine hydroxyamino acids, is associated with cell proliferation. PMID- 1639826 TI - The relationship of mechanical properties to morphology in patellar tendon autografts after posterior cruciate ligament replacement in sheep. AB - In a sheep model the posterior cruciate ligament (PCL) was replaced by a patellar tendon autograft (PTAG) using the central one-third of the ipsilateral patellar tendon (PT). The sheep were sacrificed at 16, 26, 52 and 104 weeks postoperation. The PTAG, and, as controls, the contralateral PCL and PT were harvested. These were examined using biomechanical testing as well as light and transmission electron microscopy, including immunohistological techniques. The material properties (maximum stress, elastic modulus) were compared to the morphological features. The cellular distribution, the distribution of glycosaminoglycans (GAGs), the collagen fibril diameter and the occurrence of Type III collagen were studied. Prior to transplantation, the PTAG was shown to be superior in maximum stress (57.2 +/- 5.5 MPa vs 41.3 +/- 1.9 MPa) and elastic modulus (368.8 +/- 49.3 MPa vs 172.3 +/- 14.6 MPa) to the PCL. The early decline in material properties of the PTAG (maximum stress 22% and elastic modulus 42% of the control) after free grafting paralleled a cell- and capillary-rich PTAG tissue with remnants of necrosis and a poorly organized extracellular matrix. Two years after implantation, with progressive alignment of the tissue matrix, maximum stress and elastic modulus acquired approximately 60 and 70% of the control, respectively. However, there was also an evidence of degenerative changes characterized by acellular areas, loss of the normal bundling pattern of collagen fibers and abnormal accumulation of GAGs. Ultrastructurally, there was a predominant shift to thin collagen fibrils in the PTAG compared to PCL and PT, both consisting of thick and thin collagen fibrils. Thin fibrils were demonstrated to be, in part, split thick fibrils as well as newly formed fibrils. Most of these thin fibrils revealed a positive reaction with antibodies to Type III collagen. PMID- 1639827 TI - Water content alters viscoelastic behaviour of the normal adolescent rabbit medial collateral ligament. AB - Testing environment is an important factor in the outcome of mechanical tests on connective tissue. The purpose of this investigation was to determine the effect of ligament water content on ligament mechanical behaviour by altering the test environment. Water content of medial collateral ligament (MCLs) from 19 three month-old New Zealand White rabbits was varied in subsets of ligaments pairs by means of immersion in 2, 10 or 25% sucrose or 0.9% phosphate-buffered saline (PBS) solutions for 1 h. One knee joint was cycled 50 times in the designated solution (experimental), while the contralateral knee (uncycled control) was simultaneously soaked in the same tank. Following cycling, the water contents of both test and control ligaments were determined. Water contents of 22 normal MCLs were determined immediately post-sacrifice and served as 'normal water content' controls. Normalized peak cyclic load changes were used as a measure of the viscoelastic behaviour of each MCL. Results demonstrated that only ligaments soaked (but not cycled) in a 10% sucrose solution had water contents (60.5 +/- 2.5%) which were statistically similar to the 22 fresh normal MCLs (63.9 +/- 6.0%). Ligaments soaked in PBS (74.0 +/- 1.3%) or 2% sucrose (69.2 +/- 2.3%) had significantly higher water contents compared to fresh normal MCLs. Ligaments with higher water contents (e.g. soaked in PBS or 2% sucrose) demonstrated greater cyclic load relaxation compared to ligaments with lower contents (e.g. soaked in 25 or 10% sucrose). Different fluid test environments can significantly alter ligament water content and, in turn, significantly affect ligament viscoelastic behaviour. PMID- 1639828 TI - Impedance response characteristics of the primate Mucaca mulatta exposed to seated whole-body gz vibration. AB - A mathematical model was used to quantify and describe the variability in the mechanical impedance response of the Rhesus monkey subjected to vibrations in the range 3-20 Hz at 0.5 g peak acceleration. Due to the similarities in response, a two-mass, one-degree-of-freedom (DOF) model was selected and the associated mechanical parameters determined using a nonlinear least-squares optimization program. For the six tests conducted on each of the four subjects, appreciable parameter variations were observed within a subject; however, the majority of the mean parameter values among different subjects and among the repeated tests on the population were within +/- 1 S.D. of each other. Significant differences were observed in the stiffness coefficient and the total mass among different subjects, and in the mass ratio (between inert and sprung masses) among the repeated tests. Variations in the profile shapes following resonance were described and limited by changes in the mass ratio and the damping factor. Higher mass ratios (greater than 1.0) were associated with lower damping factors (less than 0.50). The impedance response beyond resonance approached the response described by the impedance of the inert mass and the damper elements of the model combined in parallel, and supported the assumption that the lower torso was rigidly attached to the seat. Physically, the reactive force produced by the upper torso increasingly diminished following resonance, due to the load transmission/attenuation characteristics of the spinal structures at 0.5 g peak acceleration. The impedance measured at the seat becomes dominated by the transmitted damping force associated with the spine and the force generated by the rigid lower-torso mass. PMID- 1639829 TI - Evaluation of linear finite-element analysis models' assumptions for external fixation devices. AB - Linear finite-element models (FEMs) have enjoyed an increased use in orthopaedic research, including the use for modeling external fixation devices. These fixator FEMs depend on a number of basic assumptions concerning the overall fixation frame stability and the components' rigidity. Among the more important ones are: (i) rigid fixation at both ends of the pin and sidebar; (ii) that the sidebar can be treated essentially as a rigid entity, with all bending occurring in the bone pins; and (iii) that the system can be treated as linearly elastic. Prior work done by the authors questions some of these assumptions. Thus, this study sought an empirical evaluation of the validity of some of these a priori assumptions. A Hoffmann single half-frame was tested in its standard form and then according to a stepwise protocol wherein the frame was welded to eliminate any possible points of instability. These tests looked at the stability and rigidity in various modes (axial compression, torsion, and medial-lateral and anterior-posterior four-point bending). The basic assumptions concerning the frame stability, frame rigidity and the frame's response to loads were found to be erroneous. Component failure was common under minimal loads and statistically significant differences (p less than 0.05) of up to 75% were noted in frame rigidity among the various frame forms tested. Thus, considerable caution must be exercised when employing the FEM technique for evaluating the fixator properties. PMID- 1639830 TI - A general approach for modelling and mathematical investigation of the human upper limb. AB - This paper is an attempt to systematize and solve the problems connected with biomechanical modelling and mathematical investigation of the upper limb, when all muscles acting on the shoulder, elbow and wrist joint are included. The basic problem is the assumption of a hypothesis for the unit vectors, collinear with muscle forces. The so-called segment-lines modelling of the muscle force direction is proposed for solving this problem. This approach combines the simplicity of the straight line joining the muscle tendon origin to the insertion point, its application for the analytical description of the model and the real description of the muscle anatomical functions. The principle of the anatomically adequate moment is the general criterion for choosing the segments (straight and curvilinear sections) by which the direction of the muscle action is replaced. The different optimization techniques which are used for solving the statically indeterminate problem, formulated for musculoskeletal biomechanical models, are considered. Aiming to obtain strictly positive and continuous solutions for the muscle forces moduli, the application of the Lagrange multipliers method is proposed. The possibility of applying different optimization criteria is explored. A general conclusion may be formulated: if there exists any criterion which is independent of the joint angles, it follows than that it must be dependent on the joint reactions and, in addition, it must be nonlinearly dependent on the muscle forces moduli. PMID- 1639831 TI - Collagen fiber orientation and geometry effects on the mechanical properties of secondary osteons. AB - The effects of collagen fiber orientation and osteon geometry on the mechanical properties of secondary osteons under axial compression/tension and combined loadings (compression, bending and torsion) were investigated using a composite beam finite-element model. Three cross-sectional shapes of secondary osteons were studied to show the effect of geometry. The results of stiffness are presented using the tension and compression properties for each lamella. The model shows that the mechanical properties of osteons are enhanced in bending and torsion when collagen fibers are oriented within 30 degrees of the loading axis. Osteons with alternating lamellar orientation are not well adapted to resist torsional moments, but alternate collagen fiber orientation has virtually no effect on the bending stiffness of osteons. Fiber orientation affects the mechanical properties less significantly when osteons are non-circular. Collagen fiber orientation and osteon geometry interact to determine the mechanical behavior of the osteon, and may act in a compensatory manner in the adaptive process. PMID- 1639832 TI - Energy transformations in human movement by contact. AB - This study focuses on the transformation of energy in multilinkage systems by a deliberate use of the contact with the ground, leading to a derivation of the directional change of translational velocity of the body's center of mass. The coefficient of friction on the surface on which the impact occurs, and its effect on the overall movement, is studied for general multilinkage systems undergoing impact. The effect of surface friction is made apparent via simulation studies for a two-link example, where two interesting conditions arise: slippage or no slippage on the surface at impact. It is found that once the system stops on the surface, the translational energy increases as the angular velocity increases. Likewise, it is seen that the rotational energy after impact increases as the angular velocity of the first link increases, but the rate of increase of energy is less in the case where the system stops on the ground with no slippage. PMID- 1639833 TI - The influence of dynamic factors on triaxial net muscular moments at the L5/S1 joint during asymmetrical lifting and lowering. AB - Asymmetrical lifting and lowering are predominant activities in the workplace. Mechanical causes are suggested for many back injuries and the dynamic conditions within which spine loading occurs are related to spine loading increase. More data on tridimensional biomechanical lumbar spine loading during asymmetrical lifting and lowering are needed. A tridimensional dynamic multisegment model was developed to compute spinal loading for asymmetrical box-handling situations. The tridimensional positions of the anatomical markers were generated by a direct linear transformation algorithm adapted for the processing of data from two real and two virtual views (mirrors). Two force platforms measured the external forces. Five male subjects performed three variations (slow, fast and accelerated) of asymmetric lifting and two variations (slow and fast) of asymmetric lowering. The torsional, extension/flexion and lateral bending net muscular moments at the L5/S1 joint were computed and peak values selected for statistical analysis. For the lifting task, the fast and accelerated conditions showed significant increases over the slow condition for torsion, extension/flexion and lateral-bending moments. The accelerated condition also showed significant increases over the fast condition for extension. A comparison between lifting and lowering tasks showed equivalent loadings for torsion and extension. The moments were compared to average maximal values measured on equivalent male subject populations by isokinetic dynamometry. This showed torsional and extension values of 30 and 83% of the maximal possible subject capacity, respectively. These results demonstrated that dynamic factors do influence the load on the spine and highlighted the influence of both lifting and lowering on the loading of the spine. This suggested that for a more complete analysis of asymmetrical handling, the maximal velocity and acceleration produced during lifting should be included. PMID- 1639834 TI - The isometric length-force models of nine different skeletal muscles. AB - The length-force relations of nine different skeletal muscles in the hindlimb of the cat were determined experimentally, with electrical stimulation of the sciatic nerve as the activation mode. It was shown that the active-, passive-, and total-force patterns varied widely among the muscles. The tibialis posterior (TP), medial and lateral gastrocnemius (MG, LG) and flexor digitorum longus (FDL) had a symmetric active-force curve, whereas the tibialis anterior (TA), peroneus brevis (PB), peroneus longus (PL), extensor digitorum longus (EDL), and soleus (SOL) had an asymmetric curve which exhibits about 25% of the maximal isometric force at extreme lengths. The SOL, EDL, and LG had a low-level passive force which appeared at short muscle length, whereas all other muscles exhibited initial passive force just before the optimal length. The total force was rising quasi-linearly for the SOL, whereas the other muscles exhibited an intermediate plateau about the optimal length. The LG and FDL had a substantial but temporary intermediate dip in the total force as the muscle was elongated past the optimal length. The elongation range of the various muscles also varied, ranging from +/- 15 to +/- 30% of the optimal length. The elongation range was symmetric for the FDL, LG, MG, TP, SOL, and EDL, and asymmetric for the PL, PB, and TA, being -12 to + 17%, -12 to + 17%, and -35 to + 12%, respectively. Two different models which incorporate muscle architecture were successfully fitted to the experimental data of the muscles except for the MG and TA. The architecture of these two muscles is highly nonhomogeneous and contains compartments with two pennation patterns or two different optimal lengths. New models, which add spatially and temporally the individual characteristics of each compartment of the muscles, were constructed for these two muscles. The new models demonstrated high correlation to the experimental data obtained from the MG and TA. It was concluded that the length-force relation varies widely among various skeletal muscles and is probably dependent on the primary function of the muscle in the context of integrated movement; this is a manifestation of architectural factors such as fiber pennation pattern and angle, cross-sectional area, ratio of muscle to tendon length, distribution of the fiber length within the muscle and compartmental pennation. PMID- 1639835 TI - A proposed tolerance criterion for diffuse axonal injury in man. AB - The head injury criterion (HIC) is currently the government-accepted head injury indicator. The HIC is not injury-specific, does not relate to injury severity, nor does it take into account variations in the brain mass or load direction. This report focuses on one type of inertial brain injury, diffuse axonal injury (DAI), and utilizes animal studies, physical model experiments, and analytical model simulations to determine the kinematics of DAI in the subhuman primate and to scale these results to man. A human injury tolerance for moderate to severe DAI, which includes the influences of rotational loads and brain mass, is proposed. PMID- 1639836 TI - Strain rate effects on tensile failure properties of the common carotid artery and jugular veins of ferrets. AB - We have recently reported the insensitivity of tensile failure properties of human cerebral bridging veins to strain rate. Due to data scattering, however, concerns remain regarding this finding. To pursue the issue further, the common carotid arteries and external and internal jugular veins from seven ferrets were stretched longitudinally in vitro at either a low strain rate of 0.2-2.0 s-1 or a high rate of approximately 200 s-1. The ultimate stretch ratios and loads were found to be independent of strain rate in all the vessels tested. Therefore, the present results appear to support our previous finding on human bridging veins. PMID- 1639837 TI - A study on the constitutive equation of blood. AB - This paper proposes and studies a new three-parameter constitutive equation for whole human blood, tau = tau y+eta 2 gamma 1/2 + eta 1 gamma. The model aims at a proper description of the shear thinning behavior of blood at both low and high shear rates. While empirically based, it relies on continuum constitutive theories. The model has been verified by fitting the experimental data available in the literature using the weighted least squares. Results show that the proposed model fits the experimental data with nearly constant parameters in a wide shear range, and with average deviations epsilon less than 6.24%. Formulae to calculate the velocity profile and flow rate of the proposed model in a straight tube flow were deduced. Compared to Casson's and Newtonian models, it is concluded that the proposed model is more effective in describing the shear thinning behavior of blood within a wide shear range. PMID- 1639838 TI - Pulsatile flow visualization in a model of the human abdominal aorta and aortic bifurcation. AB - The infrarenal abdominal aorta and aortic bifurcation are frequent sites of atherosclerosis. The local hemodynamics are considered to be atherogenetic factors; a detailed description of these flow fields is, therefore, essential to understand their relationship to atherosclerosis. The aim of this study was, therefore, to provide such detailed information using a flow visualization technique in an anatomically realistic flow model of the abdominal aorta and its main branches in which the complex pulsatile flow waveforms and flow rates were simulated for two physiologic flow conditions (rest and exercise). At rest, the particle path lines in the suprarenal abdominal aorta were straight with no visible signs of flow reversal. Vortices were initiated opposite to the main branches. In the infrarenal aorta, large flow separation zones formed at the posterior aortic wall and at the lateral walls in the aortic bifurcation during systolic deceleration, and flow reversal was present during diastole. Under exercise conditions, the particle path lines were straight, and only slight flow reversal was seen. This study emphasizes, that rather than being a straight tube with forward-moving fluid, the abdominal aorta has to be considered as a complex part of the arterial tree. Distinct local hemodynamic qualities of importance for explaining atherogenesis were pointed out. At rest, the suprarenal abdominal aorta had much less complicated flow characteristics than the infrarenal abdominal aorta where the distal, posterior vessel wall and the lateral walls of the bifurcation were sites of flow patterns thought to be associated with atherosclerosis. During exercise, the infrarenal flow patterns changed dramatically away from the flow patterns associated with the induction of atherosclerosis. PMID- 1639839 TI - Myofilament lengths of cat skeletal muscle: theoretical considerations and functional implications. AB - The cat is the primary model for neuromuscular research. However, sarcomere geometry, in particular thin-myofilament lengths of cat skeletal muscles, is not known, thus preventing adequate muscle modeling on the sarcomere level. The purpose of this study was to determine thin-myofilament lengths in cat skeletal muscle. It was found that average thin-myofilament lengths of cat tibialis anterior muscles (1.12 microns) were larger than the average values reported for frog (approximately 0.95 microns), rat (1.09 microns), and rabbit muscles (1.09 microns) and were smaller than the values reported for monkey (1.16 microns) and human skeletal muscles (1.27 microns). According to the cross-bridge theory of muscular contraction, this result implies that the range of sarcomere length on the ascending limb of the force-length relation for cat muscle is between those of frog, rat, and rabbit on the one side and monkey and human on the other side. It is speculated that the differences in thin-myofilament lengths of different animals are related to the functional demands of these muscles in everyday movement tasks. Isolated experimental observations appear to support this speculation. PMID- 1639840 TI - Transport of microinjected alcohol oxidase from Pichia pastoris into vesicles in mammalian cells: involvement of the peroxisomal targeting signal. AB - This report describes the microinjection of a purified peroxisomal protein, alcohol oxidase, from Pichia pastoris into mammalian tissue culture cells and the subsequent transport of this protein into vesicular structures. Transport was into membrane-enclosed vesicles as judged by digitonin-permeabilization experiments. The transport was time and temperature dependent. Vesicles containing alcohol oxidase could be detected as long as 6 d after injection. Coinjection of synthetic peptides containing a consensus carboxyterminal tripeptide peroxisomal targeting signal resulted in abolition of alcohol oxidase transport into vesicles in all cell lines examined. Double-label experiments indicated that, although some of the alcohol oxidase was transported into vesicles that contained other peroxisomal proteins, the bulk of the alcohol oxidase did not appear to be transported to preexisting peroxisomes. While the inhibition of transport of alcohol oxidase by peptides containing the peroxisomal targeting signal suggests a competition for some limiting component of the machinery involved in the sorting of proteins into peroxisomes, the organelles into which the majority of the protein is targeted appear to be unusual and distinct from endogenous peroxisomes by several criteria. Microinjected alcohol oxidase was transported into vesicles in normal fibroblasts and also in cell lines derived from patients with Zellweger syndrome, which are unable to transport proteins containing the ser-lys-leu-COOH peroxisomal targeting signal into peroxisomes (Walton et al., 1992). The implications of this result for the mechanism of peroxisomal protein transport are discussed. PMID- 1639841 TI - PDGF-AA and PDGF-BB biosynthesis: proprotein processing in the Golgi complex and lysosomal degradation of PDGF-BB retained intracellularly. AB - Platelet-derived growth factor is a potent mitogen for cells of mesenchymal origin. It is made up of two polypeptide chains (A and B) combined in three disulfide-linked dimeric forms (AA, AB, and BB). Here, the biosynthesis and proteolytic processing of the two homodimeric forms of PDGF (AA and BB) were studied in CHO cells stably transfected with A-chain (short splice version) or B chain cDNA. PDGF-AA was processed to a 30-kD molecule which was secreted from the cells. In contrast, PDGF-BB formed two structurally distinct end products; a minor secreted 30-kD form and a major cell-associated 24-kD form. Immunocytochemical studies at light- and electron-microscopical levels revealed presence of PDGF in the Golgi complex, in lysosomes, and to a smaller extent in the ER. From analysis of cells treated with brefeldin A, an inhibitor of ER to Golgi transport, it was concluded that dimerization occurs in the ER, whereas the proteolytic processing of PDGF-AA and PDGF-BB precursors normally occurs in a compartment distal to the ER. Exposure of the cultures to the lysosomal inhibitor chloroquine led to an increased cellular accumulation of PDGF-BB, as determined both by metabolic labeling experiments and immunocytochemical methods, indicating that the retained form of PDGF-BB is normally degraded in lysosomes. Structural analysis of the two end products of PDGF-BB revealed that the secreted 30-kD form is a dimer of peptides processed as the B-chain of PDGF purified from human platelets, and that the retained 24-kD form is made up of subunits additionally processed in the NH2-terminus. Also, the 24-kD form was shown to be composed of proteolytic fragments held together by disulfide bridges. Taken together these findings suggest that the newly synthesized PDGF A- and B-chains are dimerized in the ER and thereafter transferred to the Golgi complex for proteolytic processing. From there, PDGF-AA is carried in vesicles to the cell surface for release extracellularly by exocytosis. A smaller part of PDGF-BB (the 30-kD form) is handled in a similar way, whereas the major part (the 24-kD form) is generated by additional proteolysis in the Golgi complex, from which it is slowly carried over to lysosomes for degradation. PMID- 1639842 TI - Protein targeting via the "constitutive-like" secretory pathway in isolated pancreatic islets: passive sorting in the immature granule compartment. AB - We have suggested the existence of a novel "constitutive-like" secretory pathway in pancreatic islets, which preferentially conveys a fraction of newly synthesized C-peptide, insulin, and proinsulin, and is related to the presence of immature secretory granules (IGs). Regulated exocytosis of IGs results in an equimolar secretion of C-peptide and insulin; however an assay of the constitutive-like secretory pathway recently demonstrated that this route conveys newly synthesized C-peptide in molar excess of insulin (Arvan, P., R. Kuliawat, D. Prabakaran, A.-M. Zavacki, D. Elahi, S. Wang, and D. Pilkey. J. Biol. Chem. 266:14171-14174). We now use this assay to examine the kinetics of constitutive like secretion. Though its duration is much shorter than the life of mature granules under physiologic conditions, constitutive-like secretion appears comparatively slow (t1/2 approximately equal to 1.5 h) compared with the rate of proinsulin traffic through the ER and Golgi stacks. We have examined whether this slow rate is coupled to the rate of IG exit from the trans-Golgi network (TGN). Escape from the 20 degrees C temperature block reveals a t1/2 less than or equal to 12 min from TGN exit to stimulated release of IGs; the time required for IG formation is too rapid to be rate limiting for constitutive-like secretion. Further, conditions are described in which constitutive-like secretion is blocked yet regulated discharge of IGs remains completely intact. Thus, constitutive-like secretion appears to represent an independent secretory pathway that is kinetically restricted to a specific granule maturation period. The data support a model in which passive sorting due to insulin crystallization results in enrichment of C-peptide in membrane vesicles that bud from IGs to initiate the constitutive-like secretory pathway. PMID- 1639843 TI - Osmotic stress and the yeast cytoskeleton: phenotype-specific suppression of an actin mutation. AB - In the yeast Saccharomyces cerevisiae, actin filaments function to direct cell growth to the emerging bud. Yeast has a single essential actin gene, ACT1. Diploid cells containing a single copy of ACT1 are osmosensitive (Osms), i.e., they fail to grow in high osmolarity media (D. Shortle, unpublished observations cited by Novick, P., and D. Botstein. 1985. Cell. 40:415-426). This phenotype suggests that an underlying physiological process involving actin is osmosensitive. Here, we demonstrate that this physiological process is a rapid and reversible change in actin filament organization in cells exposed to osmotic stress. Filamentous actin was stained using rhodamine phalloidin. Increasing external osmolarity caused a rapid loss of actin filament cables, followed by a slower redistribution of cortical actin filament patches. In the recovery phase, cables and patches were restored to their original levels and locations. Strains containing an act1-1 mutation are both Osms and temperature-sensitive (Ts) (Novick and Botstein, 1985). To identify genes whose products functionally interact with actin in cellular responses to osmotic stress, we have isolated extragenic suppressors which revert only the Osms but not the Ts phenotype of an act1-1 mutant. These suppressors identify three genes, RAH1-RAH3. Morphological and genetic properties of a dominant suppressor mutation suggest that the product of the wild-type allele, RAH3+, is an actin-binding protein that interacts with actin to allow reassembly of the cytoskeleton following osmotic stress. PMID- 1639844 TI - Alzheimer-like paired helical filaments and antiparallel dimers formed from microtubule-associated protein tau in vitro. AB - Recent evidence from several laboratories shows that the paired helical filaments of Alzheimer's disease brains consist mainly of the protein tau in an abnormally phosphorylated form, but the mode of assembly is not understood. Here we use EM to study several constructs derived from human brain tau and expressed in Escherichia coli. All constructs or tau isoforms are rodlike molecules with a high tendency to dimerize in an antiparallel fashion, as shown by antibody labeling and chemical crosslinking. The length of the rods is largely determined by the region of internal repeats that is also responsible for microtubule binding. One unit length of the repeat domain (three or four repeats) is around 22-25 nm, comparable to the cross-section of Alzheimer PHF cores. Constructs corresponding roughly to the repeat region of tau can form synthetic paired helical filaments resembling those from Alzheimer brain tissue. A similar self assembly occurs with the chemically cross-linked dimers. In both cases there is no need for phosphorylation of the protein. PMID- 1639845 TI - Microtubule dissassembly in vivo: intercalary destabilization and breakdown of microtubules in the heliozoan Actinocoryne contractilis. AB - In the marine heliozoan Actinocoryne contractilis, uninterrupted rods of microtubules stiffen the axopodia and the stalk. Stimulation in sea water elicits an extremely fast contraction (millisecond range) accompanied by almost complete Mt dissociation. Using high-speed cinematography and light transmittance measurements, we have studied the process of Mt disassembly in real time. In sea water, Mt disassembly follows an exponential decrease (mean half time of 4 ms) or proceeds by short steps. Cell contraction and Mt disassembly have been inhibited or slowed down through the use of artificial media. Although kinetics are slower (mean half time of 3 s), the curves of the length change against time look similar. The rapid as well as the slower process are accompanied by the formation of breakpoints on the stalk, from which disassembly proceeds. In specimens fixed during the slowed contraction, the presence across the Mt rods, of a single or multiple destabilization band that may consist of granular material and polymorphic forms of tubulin supports the hypothesis of "intercalary destabilization and breakdown" of axonemal Mts. PMID- 1639846 TI - A temperature-sensitive calmodulin mutant loses viability during mitosis. AB - Although rare, a recessive temperature-sensitive calmodulin mutant has been isolated in Saccharomyces cerevisiae. The mutant carries two mutations in CMD1, isoleucine 100 is changed to asparagine and glutamic acid 104 is changed to valine. Neither mutation alone conferred temperature sensitivity. A single mutation that allowed production of an intact but defective protein was not identified. At the nonpermissive temperature, the temperature-sensitive mutant displayed multiple defects. Bud formation and growth was delayed, but this defect was not responsible for the temperature-sensitive lethality. Cells synchronized in G1 progressed through the cell cycle and retained viability until the movement of the nucleus to the neck between the mother cell and the large bud. After nuclear movement, less than 5% of the cells survived the first mitosis and could form colonies when returned to permissive conditions. The duplicated DNA was dispersed along the spindle, extending from mother to daughter cell. Cells synchronized in G2/M lost viability immediately upon the shift to the nonpermissive temperature. At a semipermissive temperature, the mutant showed approximately a 10-fold increase in the rate of chromosome loss compared to a wild-type strain. The mitotic phenotype is very similar to yeast mutants that are defective in chromosome disjunction. The mutant also showed defects in cytokinesis. PMID- 1639847 TI - Calmodulin concentrates at regions of cell growth in Saccharomyces cerevisiae. AB - Calmodulin was localized in Saccharomyces cerevisiae by indirect immunofluorescence using affinity-purified polyclonal antibodies. Calmodulin displays an asymmetric distribution that changes during the cell cycle. In unbudded cells, calmodulin concentrates at the presumptive site of bud formation approximately 10 min before bud emergence. In small budded cells, calmodulin accumulates throughout the bud. As the bud grows, calmodulin concentrates at the tip, then disperses, and finally concentrates in the neck region before cytokinesis. An identical staining pattern is observed when wild-type calmodulin is replaced with mutant forms of calmodulin impaired in binding Ca2+. Thus, the localization of calmodulin does not depend on its ability to bind Ca2+ with a high affinity. Double labeling of yeast cells with affinity-purified anti calmodulin antibody and rhodamine-conjugated phalloidin indicates that calmodulin and actin concentrate in overlapping regions during the cell cycle. Furthermore, disrupting calmodulin function using a temperature-sensitive calmodulin mutant delocalizes actin, and act1-4 mutants contain a random calmodulin distribution. Thus, calmodulin and actin distributions are interdependent. Finally, calmodulin localizes to the shmoo tip in cells treated with alpha-factor. This distribution, at sites of cell growth, implicates calmodulin in polarized cell growth in yeast. PMID- 1639848 TI - H and T subunits of acetylcholinesterase from Torpedo, expressed in COS cells, generate all types of globular forms. AB - We analyzed the production of Torpedo marmorata acetylcholinesterase (AChE) in transfected COS cells. We report that the presence of an aspartic acid at position 397, homologous to that observed in other cholinesterases and related enzymes (Krejci, E., N. Duval, A. Chatonnet, P. Vincens, and J. Massoulie. 1991. Proc. Natl. Acad. Sci. USA. 88:6647-6651), is necessary for catalytic activity. The presence of an asparagine in the previously reported cDNA sequence (Sikorav, J.L., E. Krejci, and J. Massoulie. 1987. EMBO (Eur. Mol. Biol. Organ.) J. 6:1865 1873) was most likely due to a cloning error (codon AAC instead of GAC). We expressed the T and H subunits of Torpedo AChE, which differ in their COOH terminal region and correspond respectively to the collagen-tailed asymmetric forms and to glycophosphatidylinositol-anchored dimers of Torpedo electric organs, as well as a truncated T subunit (T delta), lacking most of the COOH terminal peptide. The transfected cells synthesized similar amounts of AChE immunoreactive protein at 37 degrees and 27 degrees C. However AChE activity was only produced at 27 degrees C and, even at this temperature, only a small proportion of the protein was active. We analyzed the molecular forms of active AChE produced at 27 degrees C. The H polypeptides generated glycophosphatidylinositol-anchored dimers, resembling the corresponding natural AChE form. The cells also released non-amphiphilic dimers G2na. The T polypeptides generated a series of active forms which are not produced in Torpedo electric organs: G1a, G2a, G4a, and G4na cellular forms and G2a and G4na secreted forms. The amphiphilic forms appeared to correspond to type II forms (Bon, S., J. P. Toutant, K. Meflah, and J. Massoulie. 1988. J. Neurochem. 51:776-785; Bon, S., J. P. Toutant, K. Meflah, and J. Massoulie. 1988. J. Neurochem. 51:786-794), which are abundant in the nervous tissue and muscles of higher vertebrates (Bon, S., T. L. Rosenberry, and J. Massoulie. 1991. Cell. Mol. Neurobiol. 11:157-172). The H and T catalytic subunits are thus sufficient to account for all types of known AChE forms. The truncated T delta subunit yielded only non-amphiphilic monomers, demonstrating the importance of the T COOH-terminal peptide in the formation of oligomers, and in the hydrophobic character of type II forms. PMID- 1639849 TI - A cytomechanical investigation of neurite growth on different culture surfaces. AB - We have examined the relationship between tension, an intrinsic stimulator of axonal elongation, and the culture substrate, an extrinsic regulator of axonal elongation. Chick sensory neurons were cultured on three substrata: (a) plain tissue culture plastic; (b) plastic treated with collagen type IV; and (c) plastic treated with laminin. Calibrated glass needles were used to increase the tension loads on growing neurites. We found that growth cones on all substrata failed to detach when subjected to two to threefold and in some cases 5-10-fold greater tensions than their self-imposed rest tension. We conclude that adhesion to the substrate does not limit the tension exerted by growth cones. These data argue against a "tug-of-war" model for substrate-mediated guidance of growth cones. Neurite elongation was experimentally induced by towing neurites with a force-calibrated glass needle. On all substrata, towed elongation rate was proportional to applied tension above a threshold tension. The proportionality between elongation rate and tension can be regarded as the growth sensitivity of the neurite to tension, i.e., its growth rate per unit tension. On this basis, towed growth on all substrata can be described by the simple linear equation: elongation rate = sensitivity x (applied tension - tension threshold) The numerical values of tension thresholds and neurite sensitivities varied widely among different neurites. On all substrata, thresholds varied from near zero to greater than 200 mudynes, with some tendency for thresholds to cluster between 100 and 150 mudynes. Similarly, the tension sensitivity of neurites varied between 0.5 and 5.0 microns/h/mudyne. The lack of significant differences among sensitivity or threshold values on the various substrata suggest to use that the substratum does not affect the internal "set points" of the neurite for its response to tension. The growth cone of chick sensory neurons is known to pull on its neurite. The simplest cytomechanical model would assume that both growth cone mediated elongation and towed growth are identical as far as tension input and elongation rate are concerned. We used the equation above and mean values for thresholds and sensitivity from towing experiments to predict the mean growth cone-mediated elongation rate based on mean rest tensions. These predictions are consistent with the observed mean values. PMID- 1639850 TI - Plakoglobin, or an 83-kD homologue distinct from beta-catenin, interacts with E cadherin and N-cadherin. AB - E- and N-cadherin are members of a family of calcium-dependent, cell surface glycoproteins involved in cell-cell adhesion. Extracellularly, the transmembrane cadherins self-associate, while, intracellularly, they interact with the actin based cytoskeleton. Several intracellular proteins, collectively termed catenins, have been noted to co-immunoprecipitate with E- and N-cadherin and are thought to be involved in linking the cadherins to the cytoskeleton. Two catenins have been identified recently: a 102-kD vinculin-like protein (alpha-catenin) and a 92-kD Drosophila armadillo/plakoglobin-like protein (beta-catenin). Here, we show that plakoglobin, or an 83-kD plakoglobin-like protein, co-immunoprecipitates and colocalizes with both E- and N-cadherin. The 83-kD protein is immunologically distinct from the 92-kD beta-catenin and, because of its molecular mass, likely represents the cadherin-associated protein called gamma-catenin. Thus, two different members of a plakoglobin family associate with N- and E-cadherin and, together with the 102-kD alpha-catenin, appear to participate in linking the cadherins to the actin-based cytoskeleton. PMID- 1639851 TI - The vertebrate adhesive junction proteins beta-catenin and plakoglobin and the Drosophila segment polarity gene armadillo form a multigene family with similar properties. AB - Three proteins identified by quite different criteria in three different systems, the Drosophila segment polarity gene armadillo, the human desmosomal protein plakoglobin, and the Xenopus E-cadherin-associated protein beta-catenin, share amino acid sequence similarity. These findings raise questions about the relationship among the three molecules and their roles in different cell-cell adhesive junctions. We have found that antibodies against the Drosophila segment polarity gene armadillo cross react with a conserved vertebrate protein. This protein is membrane associated, probably via its interaction with a cadherin-like molecule. This cross-reacting protein is the cadherin-associated protein beta catenin. Using anti-armadillo and antiplakoglobin antibodies, it was shown that beta-catenin and plakoglobin are distinct molecules, which can coexist in the same cell type. Plakoglobin interacts with the desmosomal glycoprotein desmoglein I, and weakly with E-cadherin. Although beta-catenin interacts tightly with E cadherin, it does not seem to be associated with either desmoglein I or with isolated desmosomes. Anti-armadillo antibodies have been further used to determine the intracellular localization of beta-catenin, and to examine its tissue distribution. The implications of these results for the structure and function of different cell-cell adhesive junctions are discussed. PMID- 1639852 TI - Cadherin-mediated cell-cell adhesion is perturbed by v-src tyrosine phosphorylation in metastatic fibroblasts. AB - Rat 3Y1 cells acquire metastatic potential when transformed with v-src, and this potential is enhanced by double transformation with v-src and v-fos (Taniguchi, S., T. Kawano, T. Mitsudomi, G. Kimura, and T. Baba. 1986. Jpn. J. Cancer Res. 77:1193-1197). We compared the activity of cadherin cell adhesion molecules of normal 3Y1 cells with that of v-src transformed (SR3Y1) and v-src and v-fos double transformed (fosSR3Y1) 3Y1 cells. These cells expressed similar amounts of P-cadherin, and showed similar rates of cadherin-mediated aggregation under suspended conditions. However, the aggregates or colonies of these cells were morphologically distinct. Normal 3Y1 cells formed compacted aggregates in which cells are firmly connected with each other, whereas the transformed cells were more loosely associated, and could freely migrate out of the colonies. Overexpression of exogenous E-cadherin in these transformed cells had no significant effect on their adhesive properties. We then found that herbimycin A, a tyrosine kinase inhibitor, induced tighter cell-cell associations in the aggregates of the transformed cells. In contrast, vanadate, a tyrosine phosphatase inhibitor, inhibited the cadherin-mediated aggregation of SR3Y1 and fosSR3Y1 cells but had little effect on that of normal 3Y1 cells. These results suggest that v-src-mediated tyrosine phosphorylation perturbs cadherin function directly or indirectly, and the inhibition of tyrosine phosphorylation restores cadherin action to the normal state. We next studied tyrosine phosphorylation on cadherins and the cadherin-associated proteins, catenins. While similar amounts of catenins were expressed in all of these cells, the 98-kD catenin was strongly tyrosine phosphorylated only in SR3Y1 and fosSR3Y1 cells. Cadherins were also weakly tyrosine phosphorylated only in the transformed cells. The tyrosine phosphorylation of these proteins was enhanced by vanadate, and inhibited by herbimycin A. Thus, the tyrosine phosphorylation of the cadherin-catenin system itself might affect its function, causing instable cell-cell adhesion. PMID- 1639853 TI - Altered metabolic and adhesive properties and increased tumorigenesis associated with increased expression of transforming growth factor beta 1. AB - Transforming growth factor-beta (TGF-beta) is a potent mediator of cell proliferation and extracellular matrix formation, depending on the cell type and the physiological conditions. TGF-beta is usually secreted in a "latent" complex that needs activation before it can exert its effects. Several observations correlate increased expression of TGF-beta 1 with tumorigenesis. To evaluate the physiological relevance of increased TGF-beta 1 synthesis in tumor cells we established cell clones overexpressing TGF-beta 1 and observed the resulting physiological changes in TGF-beta overproducing cells in vitro and in vivo. As a model system we used the human E1A-transformed 293 tumor cells, which are insensitive to the direct growth modulatory effects of TGF-beta. The selection of this cell line allows an assessment of physiological alterations independent of TGF-beta induced proliferative changes. The use of two TGF-beta 1 expression vectors containing either the natural or a modified TGF-beta 1 precursor cDNA permitted the establishment of separate 293 cell lines overexpressing latent or active TGF-beta. Comparison of the resulting changes in glycolytic rate, adhesiveness and integrin and plasminogen activator expression established that, in vitro, both types of clones behaved similarly, indicating that expression of latent TGF-beta induces autocrine changes in the tumor cells and thus suggesting that some level of cell-associated activation occurs. TGF-beta overexpression resulted in an increased metabolic rate due to enhanced glycolysis, a property long associated with tumor cells. This increased glycolysis was not associated with altered proliferation. Cells overexpressing TGF-beta also displayed enhanced fibronectin mRNA and plasminogen activator synthesis and increased adhesiveness in vitro. They showed enhanced survival when plated sparsely on plastic in the absence of serum, and attached more readily to laminin. In addition, synthesis of several beta 1 integrins, in particular the alpha 1/beta 1, alpha 2/beta 1, and alpha 3/beta 1, all of which recognize laminin, were enhanced. Finally, cells overexpressing active TGF-beta, but not latent TGF-beta, also showed increased tumorigenicity in nude mice. Thus, an increase in endogenous TGF-beta synthesis confers several proliferation-independent phenotypic changes which may be of significance for the survival of the tumor cell inoculum or its subsequent growth, and for tumor formation and development. In the case of cells expressing active TGF-beta, the release of active TGF-beta into the vicinity of the tumor cells may also result in a more hospitable environment for tumor growth. PMID- 1639854 TI - Targeted disruption of the tissue inhibitor of metalloproteinases gene increases the invasive behavior of primitive mesenchymal cells derived from embryonic stem cells in vitro. AB - The metalloproteinase family of proteolytic enzymes can degrade extracellular matrix and facilitate invasive migration. This class of enzymes is specifically inhibited by the tissue inhibitor of metalloproteinases (TIMP-1). Using homologous recombination, we have disrupted the gene encoding TIMP-1 in pluripotent embryonic stem cells. Because the TIMP-1 gene is X linked and is hemizygous in embryonic stem cells, we have been able to study the effect of this mutation in culture. Using a basement membrane invasion assay, we found that the mutant cells, differentiated in low concentrations of serum with retinoic acid, were more invasive than their normal cell counterparts, and that this was specifically reversed by adding exogenous TIMP-1 protein. The invasive cell population had characteristics of an early population of primitive mesenchymal cells, including expression of vimentin and a transient period of invasiveness from 4-8 d after initiation of differentiation. Therefore, metalloproteinase activity can be rate limiting for cell invasion. PMID- 1639855 TI - Autocrine action of amphiregulin in a colon carcinoma cell line and immunocytochemical localization of amphiregulin in human colon. AB - Amphiregulin (AR) is a newly discovered glycosylated, 84-amino acid residue polypeptide growth regulator which has sequence homology to the EGF family of proteins. To obtain immunological reagents to study the biological role of AR, two synthetic peptides containing sequences corresponding to distinct regions of AR were used to generate polyclonal antibodies in rabbits. One preparation of antipeptide antibodies directed against residues 26-44 of AR (AR-Ab2) was most effective in the detection of native AR, whereas another preparation of antibodies against residues 8-26 (AR-Ab1) was found to be most efficacious in the detection of AR in formalin-fixed and paraffin-embedded tissues. The growth of a colon carcinoma cell line, Geo, which proliferates autonomously under serum-free conditions, was stimulated by the exogenous addition of AR or EGF. Half-maximal stimulation of this growth was observed at 40 and 200 pM of EGF and AR, respectively. A mAb to the extracellular domain of the EGF receptor blocked the stimulation of cell proliferation induced by the exogenous addition of AR, suggesting that this stimulation was mediated via the EGF receptor. Geo cells were found to constitutively express significant levels of the AR mRNA transcript as determined by analysis of the polymerase chain reaction-amplified cDNA product and AR protein was detected immunocytochemically using the AR-Ab1 antibodies in these cells. AR was immunoprecipitated specifically using the AR-Ab2 antibodies from the conditioned medium of Geo cells, which had been metabolically labeled with [35S]cysteine. The secreted AR migrated as a broad band (18.5-22.5 kD) with a median molecular weight of approximately 20.7 kD in SDS-PAGE. Immunospecific removal of AR from serum-free medium conditioned by the Geo cells and readdition of the AR-depleted medium to Geo cells resulted in an approximately 40% inhibition of cell growth relative to controls. Furthermore, the growth of the Geo cells was also inhibited by approximately 50% by the addition of the anti-EGF receptor mAb alone. These results indicate that AR and the EGF receptor are involved in the autocrine growth of these cells and suggests that AR may act through the EGF receptor via an extracellular autocrine loop. To study the expression of AR in human colon in vivo, AR was localized immunocytochemically in formalin-fixed, paraffin-embedded sections from normal and malignant human colon using the AR-Ab1 antibodies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1639856 TI - Correction. Molecular cloning of a novel hyaluronan receptor that mediates tumor cell motility. PMID- 1639857 TI - Interleukin 1: the patterns of translation and intracellular distribution support alternative secretory mechanisms. AB - Interleukin-1 (IL-1) is synthesized as a 31 kDa precursor protein, whose multiple extracellular activities are attributed to receptor binding of a processed, carboxy-terminal 17 kDa peptide. Unlike other secreted proteins, the IL-1 precursor lacks a hydrophobic leader sequence and is not found in organelles composing the classical secretory pathway. In order to further clarify the intracellular processing of IL-1, we studied its site of synthesis in human monocytes. Secreted and integral membrane proteins are translated on membrane bound polyribosomes, while intracellular proteins are translated on free polyribosomes. Free and membrane-bound polysomes were isolated from Lipid A stimulated monocyte lysates and immunoblotted using antibodies specific to the N terminal regions of the IL-1 alpha and beta precursors. Free polysome fractions showed multiple small bands consistent with nascent peptide chains; membrane bound polysomes yielded no detectable IL-1. Polysome fractions were then analyzed by immunoelectron microscopy; nascent IL-1 alpha and beta peptide chains were readily seen emerging from cytoskeletal-associated free polyribosomes, but not membrane-bound polyribosomes. Electron microscopic in situ hybridization revealed IL-1 mRNA chains attached to cytoskeletal-associated free, but not membrane-bound polyribosomes. The intracellular distribution of the fully synthesized IL-1 beta precursor was studied in human mesangial cells (HMC), whose cytoskeletal organization is more readily evaluated than that of monocytes. Dual immunofluorescence microscopy of these cells revealed a complex intracellular distribution of the fully synthesized 31 kDa IL-1 precursors. IL-1 was asymmetrically distributed between cytosolic, microtubule, and nuclear compartments, without association with actin or intermediate filaments. This demonstration of the sites of IL-1 synthesis and patterns of intracellular distribution provide further evidence for an extracellular release mechanism which is clearly distinct from the classical secretory pathway. PMID- 1639858 TI - Modulation of mRNA levels during human keratinocyte differentiation. AB - Cultures of human keratinocytes provide an excellent model system in which to study differentiation. Using the phorbol ester 12-O-tetradecanoyl-phorbol 13 acetate (TPA) and calcium, two agents known to induce keratinocyte differentiation in vitro, we examined the expression of the genes encoding c-fos, c-myc, and c-jun; involucrin, a protein precursor of the keratinocyte cornified envelope; and L-7, a ribosomal protein. Overall, at the doses studied, TPA induced a more rapid and profound differentiation than did calcium, as evaluated by culture morphology and northern blot analysis. Our studies showed a constant low level of c-fos and c-jun expression in unstimulated cells with no significant change after addition of either TPA or calcium except when transcript breakdown was inhibited by cycloheximide. The c-myc proto-oncogene, known to have a high constitutive expression in actively proliferating cells, was strongly downregulated by TPA, but calcium had no effect over a 32 hour period, consistent with the greater growth inhibition of TPA in this system. Involucrin was induced about ninefold by both TPA and calcium as early as 8 hours after stimulation, suggesting transcriptional regulation of this gene during differentiation. L-7, recently demonstrated to be downregulated in late passage human fibroblasts in an in vitro model of senescence, was also strongly downregulated by either TPA or calcium, consistent with an interrelationship between the basic cellular processes of aging and differentiation. These finding expand our knowledge of the differentiation process in human keratinocytes. PMID- 1639859 TI - Identification of multiple PKC isoforms in Swiss 3T3 cells: differential down regulation by phorbol ester. AB - The expression of members of the Ca2+ and phospholipid-dependent protein kinase (PKC) family were studied in murine Swiss 3T3 cells. In addition to PKC-alpha, the presence of immunoreactive PKC-delta, -epsilon, and zeta was detected. Treatment with 500 nM 12-0-tetradecanoylphorbol-13-acetate (TPA) led to the down regulation of alpha, delta, and epsilon isoforms, but not that of zeta. Higher concentrations of TPA similarly had no effect on the level of PKC-zeta. In contrast to PKC-alpha, the membrane localization of PKC-delta, -epsilon, and zeta was not enhanced by extraction in Ca(2+)-containing buffers, whereas acute TPA treatment increased membrane association of PKC-alpha, -delta, and -epsilon but not that of PKC-zeta. PMID- 1639860 TI - Analysis of the influences of the E5 transforming protein on kinetic parameters of epidermal growth factor binding and metabolism. AB - The E5 protein of the bovine papillomavirus induces cellular transformation when transfected into NIH 3T3 cells, and the extent of focal transformation is enhanced by cotransfection with the epidermal growth factor (EGF) receptor (Martin et al., Cell 59:21-32, 1989). To determine whether E5 affects EGF:receptor interactions we analyzed the kinetics of 125I-EGF processing using a mathematical model that enabled us to evaluate rate constants for ligand association (ka), dissociation (kd), internalization (ke), recycling (kr), and degradation (kh). These rate constants were measured in NIH 3T3 cells transfected with the human EGF receptor (ER cells) and in cells transfected with both the EGF receptor and E5 (E5/ER cells). We found that the rate constant for 125I-EGF association ka was significantly decreased in E5/ER cells, but was apparently occupancy-independent in both cell lines. The 125I-EGF dissociation rate constant kd was significantly lower in E5 transformed cells, and increased with occupancy in both cell lines. This suggests that E5 alters the receptor before or during EGF binding so that ligand association is slower; however, once complexes are formed, EGF is bound more tightly to the receptor. Rate constants for internalization ke were also found to be occupancy-dependent, although at a given level of occupancy ke was similar for both cell lines. Also, there was no apparent effect of E5 on the recycling rate constant kr. The 125I-EGF degradation rate constant kh was 30% lower in E5 transformed cells, and was occupancy independent. The overall effect of E5 is to stabilize intact EGF:receptor complexes which may alter mitogenic signaling of the receptor. PMID- 1639861 TI - Interleukin-1 beta induction of TNF-alpha gene expression: involvement of protein kinase C. AB - In the human astroglioma cell line CH235-MG, interleukin-1 beta (IL-1 beta) induces transcriptional activation of the tumor necrosis factor-alpha (TNF-alpha) gene, resulting in expression of TNF-alpha mRNA and biologically active TNF-alpha protein. This study was undertaken to elucidate intracellular signaling pathways involved in IL-1 beta induction of the TNF-alpha gene. We demonstrated that the protein kinase C (PKC) activator 4 beta-phorbol 12 beta-myristate 13 alpha acetate (PMA) in concert with Ca++ ionophore A23187 induced expression of TNF alpha mRNA and protein, whereas an inactive PMA analogue (alpha PMA) had no effect. Various cyclic nucleotide activators such as 8-Bromo cAMP, cholera toxin, and forskolin had no effect on TNF-alpha production. Two PKC inhibitors, H7 and staurosporine (SS), abrogated IL-1 beta induced TNF-alpha expression in a dose dependent fashion. Treatment of CH235-MG cells with a high concentration of PMA (1 microM) for an extended period of time (48 h) caused a greater than 90% reduction in total PKC activity. Further strengthening a role for PKC in this cytokine response is the fact that IL-1 beta was no longer able to induce TNF alpha expression in these PKC depleted cells. Last, IL-1 beta treatment produced an increase of total PKC activity in CH235-MG cells. Taken together, these data demonstrate that IL-1 beta induces TNF-alpha gene expression in CH235-MG cells in a PKC-dependent manner. PMID- 1639862 TI - Induction of fibronectin gene expression by transforming growth factor beta-1 is attenuated in bronchial epithelial cells by ADP-ribosyltransferase inhibitors. AB - Transforming growth factor-beta (TGF-beta) exerts several effects on cultured airway epithelial cells including inhibition of proliferation and stimulation of fibronectin gene expression. ADP-ribosylation is one potential regulatory mechanism of gene expression by TGF-beta. We tested this possibility by exposing cultured bovine bronchial epithelial cells to the chemical inhibitor of ADP ribosyl transferase enzymes, 3-aminobenzamide (3-AB) and, for comparison, 3 aminobenzoic acid (3-ABA), which is structurally similar to 3-AB but which does not inhibit ADP-ribosyl transferases. Exponential cell growth rate (1.2 doublings/day) or cellular morphology observed by phase contrast microscopy were not affected by 3 mM 3-AB or 3-ABA. Neither compound antagonized inhibition of cell division or induction of squamous morphology by TGF-beta 1. In contrast, the sixfold stimulation of fibronectin production by exposure of cells to 30 pM TGF beta 1 for 48 h was reduced by 50% in the presence of 3 mM 3-AB, whereas 3 mM 3 ABA had no effect. The antagonistic effect was augmented by administration of 3 AB 24 h prior to induction by TGF-beta 1. Northern blot hybridization analyses demonstrated that 3-AB, but not 3-ABA, attenuated the induction of fibronectin mRNA by TGF-beta 1 by up to 50%. These observations may implicate a role of cellular ADP-ribosylation in the regulation of some gene expression by TGF-beta. PMID- 1639863 TI - Changes in responsiveness of rat tracheal epithelial cells to transforming growth factor-beta 1 with time in culture. AB - Primary rat tracheal epithelial (RTE) cell cultures have previously been shown to be highly sensitive to growth inhibition by transforming growth factor-beta 1 (TGF beta 1) when treated within 1-2 days after plating. The purpose of the present studies was to examine the effects of TGF beta 1 on the growth of RTE cells as a function of time in culture. We found that the sensitivity of RTE cells to growth inhibition by TGF beta 1 decreased dramatically as the cultures aged. The IC50 for inhibition of colony forming efficiency was 0.18 pM when TGF beta 1 was added 24 h after cell plating. When TGF beta 1 treatment was begun on day 5 of culture, the IC50 was 3-4 pM as measured by inhibition of growth (cell number) and DNA synthesis. However, when TGF beta 1 was begun on day 19, the IC50 was 65 pM or greater than 500 pM, depending on whether inhibition of growth or DNA synthesis, respectively, was measured. TGF beta 1 accelerated cell death, as measured by exfoliation of cells, and inhibited cell proliferation. The decrease in responsiveness to TGF beta 1 in late cultures was shown to be dependent on culture age as well as on cell density. No evidence was found for inactivation or degradation of the added TGF beta 1 by the late stage cultures. Cells subcultured from late stage primary cultures remained less responsive to TGF beta 1 than subcultured cells from early cultures. Similar to its effect on proliferation, TGF beta 1 down-regulated the expression of two proliferation-related genes, c myc and transforming growth factor-alpha, in early but not late RTE cell cultures. On the other hand, fibronectin expression was increased by TGF beta 1 by about twofold at both early and late times in culture. This indicates that the changes in TGF beta 1 responsiveness with time in culture are selective, apparently affecting primarily proliferation-related events. PMID- 1639864 TI - Epidermal growth factor dependence and TGF alpha autocrine growth regulation in primary rat tracheal epithelial cells. AB - We have examined dependence of primary rat tracheal epithelial (RTE) on exogenous epidermal growth factor (EGF) and determined whether a TGF alpha autocrine pathway is operating in these cells. Primary RTE cells plated in serum free media (SFM) without EGF and bovine pituitary factor (BPE) show little proliferation compared to cultures propagated in media containing EGF/BPE (CSFM). Removal of EGF/BPE shortly after plating, however, results in significant proliferation, although plateau cell densities are reduced and cell morphology is significantly altered compared to cells propagated in CSFM. Addition of EGF and/or BPE to cultures propagated in SFM minus EGF/BPE restores maximum cell density. The concentration of TGF alpha peptide in media conditioned by cells propagated without EGF/BPE is lower than the concentration in the media of CSFM cultures. TGF alpha mRNA and protein levels are also significantly lower in cells late in culture compared to logarithmically growing cells regardless of the presence or absence of EGF/BPE. The proliferation of primary RTE cells propagated without EGF/BPE is inhibited by neutralizing TGF alpha antiserum and by a tyrphostin compound that blocks TGF alpha/EGF receptor tyrosine kinase activity. These results indicate that primary RTE cells utilize TGF alpha as an autocrine growth factor and that the autocrine pathway is regulated as a function of growth state of the cells. However, this pathway does not provide growth autonomy to primary RTE cells, since cultures remain dependent on exogenous EGF/BPE for sustained proliferation. PMID- 1639866 TI - Effect of protein and steroidal osteotropic agents on differentiation and epidermal growth factor-mediated growth of the CFK1 osseous cell line. AB - The effects of factors known to influence bone metabolism were examined using the osseous cell line CFK1. Parathyroid hormone (PTH) and dexamethasone (DEX) appeared to enhance the formation of cell foci of CFK1 cells in culture whereas retinoic acid (RA) caused a marked alteration in individual cell morphology. Bone morphogenetic protein (BMP-2) and PTH increased alkaline phosphatase activity, however, this index of differentiation was suppressed by epidermal growth factor (EGF), DEX, and RA. BMP-2 and EGF each stimulated DNA synthesis in a dose dependent manner and enhanced cell numbers, but, no synergistic response of EGF and BMP-2 was observed. PTH and DEX failed to significantly alter cell number or EGF-stimulated DNA synthesis or cell proliferation. Although RA treatment of CFK1 cells resulted in a reduction in cell number compared to control, pretreatment with RA enhanced EGF-stimulated DNA synthesis and proliferative effects. At least part of this effect was by increasing the EGF receptor binding capacity of the cells. Furthermore, using cell cycle analysis, addition of EGF stimulated the progression of RA-treated cells into the DNA synthesis (S) phase with a reduced lag time. EGF and BMP-2, therefore, appear to exert a role in the expansion dynamics of the CFK1 population although BMP-2 may also enhance differentiation. PTH and DEX may act primarily to modulate the differentiated function of the CFK1 cells. RA inhibited cell proliferation and may mediate differentiation towards a less established cell population with upregulation of EGF receptors. The CFK1 cell model may, therefore, provide insight into microenvironmental control of growth and differentiation of precursor osseous cells. PMID- 1639865 TI - Characterization of metformin transport system in NIH 3T3 cells. AB - The biochemical properties of the metformin transport system were studied in NIH 3T3 cells. 14C-metformin uptake appeared to be a sodium dependent process. Iso osmotical replacement of Na+ by choline chloride in the assay medium resulted in a decrease of metformin uptake. Amiloride (200 microM) inhibited the metformin transport by 35% in these cells. Gramicidin, a channel ionophore, was the most effective in inhibiting the metformin transport as compared to valinomycin, a mobile ion carrier, and Ca2+ ionophore (A 23187). Loading of cells with asparagine, ornithine, or polylysine did not influence the uptake process. However, the addition of lysine or arginine significantly stimulated the metformin uptake by NIH 3T3 cells. Similarly, the addition of metformin stimulated the arginine uptake by these cells, suggesting that metformin shares the y+ transport system. Metformin inhibited competitively the uptake of 14C spermidine, a molecule of the polyamine family, by NIH 3T3 cells, whereas the latter failed to influence the uptake of the former significantly by these cells. Incubation of NIH 3T3 cells in the presence of difluoromethyl-ornithine (a suicidal inhibitor of polyamine biosynthesis) stimulated the spermidine, but not the metformin, uptake by these cells. Interestingly, a prolonged incubation of these cells in the presence of metformin failed to down-regulate the spermidine transport process. The spermidine- and methylglyoxal-bis(guanylhydrazone), MGBG transport deficient (3T3MG) cells which do not accumulate exogeneous spermidine or MGBG, took up 14C-metformin. However, 14C-metformin uptake by 3T3MG cells was lower than that by normal NIH 3T3 cells. PMID- 1639867 TI - UV induction of transforming growth factor alpha in melanoma cell lines is a posttranslational event. AB - Low, mitogenic fluences of UVC (3.7-5.6 Jm-2) have previously been shown to cause increases of radioimmunoassayable transforming growth factor alpha (TGF alpha) in the medium and cells of cultures of melanocytes, melanoma lines, and HeLa cells (Ellem, K.A.O., Cullinan, M., Baumann, K.C., Dunstan, A.: Carcinogenesis 9:797 801, 1988). Here the cellular mechanism of this increase is explored by Northern blotting to detect any changes in TGF alpha mRNA levels, and the use of inhibitors of macromolecular synthesis to attempt to block the increase in TGF alpha protein. We were unable to detect any increase in TGF alpha mRNA levels attributable to UVC between 2 and 24 hours after irradiation. Inhibition of DNA synthesis (arabinosylcytosine, 10 microM), RNA synthesis (actinomycin D, 3 micrograms/ml; DRB 93 microM), or protein synthesis (cycloheximide, 10 micrograms/ml) failed to prevent the UVC induced increase in TGF alpha. We conclude that the UVC induction of TGF alpha is by a posttranslational mechanism. There was considerable discordance between the amount of TGF alpha protein and its mRNA in cultures of 15 different melanoma cell lines, which again emphasized that posttranscriptional mechanisms modulate the release of immunodetectable TGF alpha. We also found that the inhibitors themselves were capable of inducing an increase in TGF alpha in MM229 cultures. This suggests that the inhibitors and UV may effect the increase by a common mechanism, perhaps the activation of cell surface proteases as suggested for other stimuli (e.g., Pandiella, A., and Massague, J.: Proc. Natl. Acad. Sci., USA 88:1726-1730, 1991) and that the response may be part of a global response to perturbation of DNA synthesis. PMID- 1639868 TI - Distinct mechanisms of zinc uptake at the apical and basolateral membranes of caco-2 cells. AB - Zinc uptake mechanisms at the apical and basolateral membrane borders of caco-2 cells were examined. This human-derived cell line possesses many morphological and functional characteristics of absorptive small intestinal cells. By day 14, confluent and well-differentiated monolayers were formed when the cells were grown on porous polycarbonate filters. Labelled zinc was placed on the apical or basal side of the monolayer and its uptake by the cells, as well as its transport across the monolayer, were measured. Zinc uptake by the cells from the apical side was found to be a saturable process (Kt = 41 microM; Vmax = 0.3 nmols/cm2/10 min) with a diffusional term at higher concentrations (1.0 sec/cm). Apical uptake was not affected by metabolic inhibitors or potential zinc ligands. Zinc uptake from the basolateral side was concentration dependent (Kd = 1.3 sec/cm) and was partially inhibited (30%) by ouabain and vanadate, suggesting that the (Na-K) ATPase on the basolateral membrane is involved in the serosal uptake of zinc by the cell. Transport of zinc across the monolayers from the apical or basolateral compartment was concentration dependent and was not affected by metabolic inhibitors. Zinc transport from the basolateral side was greater than 2-fold greater than apical transport. Hence, separate mechanisms can be distinguished with respect to zinc uptake at the apical and basolateral membranes of caco-2 cells. PMID- 1639869 TI - Insulin-like growth factor-I (IGF-I) stimulates protein synthesis and collagen gene expression in monolayer and lattice cultures of fibroblasts. AB - Fibroblasts cultivated in three-dimensional tissue-like matrices are characterized by a slowed metabolism and a decrease of protein synthesis, unless they are submitted to physical tensions. We checked the effects of insulin like growth factor-I (IGF-I), known as a potent stimulator of mitogenesis and protein synthesis for many cell types, in various models of cultures: confluent monolayers, collagen lattices, non-retracting or retracting fibrin lattices. IGF I (1-100 ng.ml-1) had no effect on cell divisions in lattice cultures. It was able to stimulate collagen lattice retraction when the medium was supplemented with low concentrations of serum. IGF-I at 10 or 100 ng.ml-1 stimulated collagen and non-collagen syntheses in all culture systems, but stimulation of collagen synthesis only began at the highest concentration (100 ng.ml-1) in retracted lattices. Northern blot and dot-blot analyses of mRNAs extracted from monolayer cultures of fibroblasts showed that IGF-I stimulated pro alpha 1(I) collagen synthesis at the pretranslational level. Cycloheximide (7.5 micrograms.ml-1) completely inhibited pro alpha 1(I) collagen gene expression induced by IGF-I. These results show that IGF-I is a potent stimulus for protein synthesis and collagen gene expression in monolayers and tridimensional cultures of fibroblasts, but that it exerts no mitogenic activity in tridimensional lattices. Synergistic associations of IGF-I with other growth factors will have to be found in order to reverse the quiescent status of fibroblasts in lattices. PMID- 1639870 TI - Influence of cyclosporine A on growth and extracellular matrix synthesis of human fibroblasts. AB - Cyclosporine A (CyA) is a powerful nonsteroidal immunosuppressive agent used to prevent graft rejection of organ and bone marrow transplants. A major side effect observed can be attributed to the fibroblast and its functions: proliferation of fibroblasts and formation of fibrotic tissue in the gingiva (fibrous hyperplasia) and in the kidney are induced. The mechanism of both is still obscure. In order to elucidate whether these side effects are due to the drug acting on human fibroblasts itself or whether they are indirect ones mediated by factors released by lymphocytes, cultures of human gingiva fibroblasts were exposed to CyA under defined in vitro conditions. Incubation with CyA for 72 hours resulted in a dose dependent stimulation of DNA synthesis, whereas glycosaminoglycan (GAG) synthesis was slightly suppressed. Long-term incubation (6 weeks) with 1 micrograms/ml CyA resulted again in stimulation of growth parameters: compared to the drug-free control, cell number increased to 168%, incorporation of 3H-thymidine into DNA to 143%, and overall protein content to 159%. Collagen and GAG synthesis were elevated to approximately 120%. When corrected for cell number or cell protein content, this represents a decline in matrix synthesis, comparable to short-term incubations. These results indicate that a direct effect of CyA on proliferation of human gingival fibroblasts is responsible for some of the observed hyperplasia. PMID- 1639871 TI - Signal transduction during liver regeneration: role of insulin and vasopressin. AB - The relationship between cell proliferation and inositol lipid turnover has been studied by comparing the steady state of inositol derivative metabolism in quiescent and regenerating rat hepatocytes isolated at 4 h (G1 phase of first cell cycle) and 24 h (onset of M phase) after partial hepatectomy. The effect of two hormones able to regulate hepatic regeneration, insulin and vasopressin, has been considered, and the results can be summarized as follows: (i) at 4 h after partial hepatectomy, the precursor incorporation into inositol polyphosphates and the particulate phospholipase C activity increase with respect to quiescent hepatocytes, whereas the content of 11, 4, 5P3 does not change, suggesting an increased turnover of this molecule in this step of cell cycle priming; (ii) 24 h after partial hepatectomy, the radioactivity linked to IP3 and IP4, as well as soluble and particulate phospholipase C activity, and IP3 content increase, suggesting the presence, at the onset of M phase, of second messenger accumulation; (iii) only 24 h after partial hepatectomy, the inositol derivative metabolism is affected by vasopressin; and (iv) insulin exerts a modulatory role on inositol polyphosphate production without involving membrane-bound PLC activity or phosphoinositide hydrolysis. These data suggest that inositol-derived signal molecules are associated with hepatic regeneration; moreover, the metabolic pathway of such compounds seems to be regulated so that only specific inositol phosphates are present in each step of the cell cycle. PMID- 1639872 TI - Competition between cell-substratum interactions and cell-cell interactions. AB - Clusterin, a glycoprotein which elicits the aggregation of a wide variety of cells (Fritz, I. B., and Burdy, K.:J. Cell Physiol., 140:18-28, 1989), has been utilized to investigate some of the factors modulating the competition between cell-substratum interactions and cell-cell interactions. We compared the responses to clusterin by anchorage-independent cells (erythrocytes) with those by anchorage-dependent TM4 cells (a cell line derived from neonatal mouse testis cells). Cells were maintained in culture in the presence of various substrata chosen to enhance cell-substratum interactions (laminin-coated wells), or to diminish cell-substratum interactions (agarose-coated wells). Results obtained showed that the aggregation of erythrocytes elicited by clusterin was independent of the nature of the substratum. In contrast, clusterin addition resulted in aggregation of anchorage-dependent TM4 cells only when TM4 cell-substratum interactions were weak. Thus, clusterin did not aggregate TM4 cells plated upon a laminin substratum, but readily aggregated TM4 cells plated upon an agarose coated substratum, independent of the sequence of addition of cells and clusterin to the culture dish. We utilized YIGSR, a peptide which competes with laminin for laminin receptors, to determine the possible role of laminin receptors on TM4 cells in the competition between cell-substratum interactions and cell-cell interactions. The presence of YIGSR did not alter responses of erythrocytes to clusterin under all conditions examined. In contrast, the responses of TM4 cells to clusterin were greatly changed. YIGSR addition resulted in the inhibition of aggregation of TM4 cells otherwise elicited by clusterin. YIGSR also prevented attachment of TM4 cells to a laminin-coated surface, but this was reversed by the presence of clusterin. We discuss the possible roles of clusterin and laminin in altering the balance in the competition between cell to cell interactions and cell to substratum interactions. PMID- 1639873 TI - Transforming growth factor-beta 1 is a heparin-binding protein: identification of putative heparin-binding regions and isolation of heparins with varying affinity for TGF-beta 1. AB - Previous studies indicated that a major factor in heparin's ability to suppress the proliferation of vascular smooth muscle cells is an interaction with transforming growth factor-beta 1 (TGF-beta 1). Heparin appeared to bind directly to TGF-beta 1 and to prevent the association of TGF-beta 1 with alpha 2 macroglobulin (alpha 2-M). The present studies indicate that 20-70% of iodinated TGF-beta 1 binds to heparin-Sepharose and the retained fraction is eluted with approximately 0.37 M NaCl. Native, unlabelled platelet TGF-beta 1, however, is completely retained by heparin-Sepharose and eluted with 0.9-1.2 M NaCl. Using synthetic peptides, the regions of TGF-beta 1 that might be involved in the binding of heparin and other polyanions were examined. Sequence analysis of TGF beta 1 indicated three regions with a high concentration of basic residues. Two of these regions had the basic residues arranged in a pattern homologous to reported consensus heparin-binding regions of other proteins. The third constituted a structurally novel pattern of basic residues. Synthetic peptides homologous to these three regions, but not to other regions of TGF-beta 1, were found to bind to heparin-Sepharose and were eluted with 0.15 M-0.30 M NaCl. Only two of these regions were capable of blocking the binding of heparin to 125I-TGF beta. Immobilization of these peptides, followed by affinity purification of heparin, indicated that one peptide was capable of isolating subspecies of heparin with high and low affinity for authentic TGF-beta 1. The ability of TGF beta 1 to bind to heparin or related proteoglycans under physiological conditions may be useful in understanding the biology of this pluripotent growth and metabolic signal. Conversely, a subspecies of heparin molecules with high affinity for TGF-beta 1 may be a factor in some of the diverse biological actions of heparin. PMID- 1639874 TI - A shrinking world. PMID- 1639875 TI - Advances in paediatric pharmacotherapy. AB - Marked differences in body composition and organ function development have been demonstrated among neonates, infants, and children versus adults. Specific dosage guidelines for the paediatric population, however, are still not available for the majority of marketed drugs. Much needs to be learned about the pharmacokinetics, pharmacodynamics, comparative efficacy and safety of drugs in infants and children. Recent developments in paediatric therapeutics include the availability of several new antibiotics for the treatment of infections including, streptococcal pharyngitis, otitis media, bacterial meningitis, herpes encephalitis, neonatal herpes, and AIDS. Corticosteroids and intravenous immunoglobulin have become important adjunctive treatments for certain infections. A variety of drugs are available to treat asthma but the mortality due to this disease is still increasing. The identification of a gene defect in patients with cystic fibrosis could lead to more effective treatment in the future. Ondansetron, marketed for use in adults only, shows promise as a more effective and safer antiemetic in children receiving cancer chemotherapy. Numerous drugs are not available in suitable dosage forms for paediatric use and extemporaneous formulations are required. Documentation on the stability of the reformulated drugs is therefore needed. Studies have shown that the methods used for intravenous delivery can influence the serum concentrations of drugs in infants and children. Large numbers of children could be saved worldwide solely with improved vaccination and control of diarrhoea. Despite this, it is encouraging to witness the continued advances being made in paediatric pharmacotherapy. PMID- 1639876 TI - Hypertension, coronary artery disease and insulin resistance--linked disorders with an impact on treatment. AB - Coronary artery disease is a very common disorder for which hypertension is a well-recognized risk factor. However many trials of antihypertensive therapy have failed to demonstrate a reduction in the incidence of coronary events. One explanation is that hypertension is a disorder associated with hyperinsulinaemia, obesity and non-insulin dependent diabetes. Furthermore certain antihypertensive drugs, notably thiazide diuretics, increase the hyperinsulinaemia and thereby increase one of the other coronary risk factors. In this review the links between hypertension and hyperinsulinaemia are explored and the mechanisms whereby an increased plasma insulin can lead to the more rapid development of coronary artery disease are explained. These observations may influence the choice of drugs used to treat hypertension. PMID- 1639877 TI - Thioethers in urine of sterilization personnel exposed to ethylene oxide. AB - Biological monitoring of exposure to ethylene oxide (EO) was carried out in 31 hospital workers in the sterilization facilities of five hospitals. The excretion of total thioethers was determined in the urine of sterilization workers. An occupational nonexposed group served as a control (n = 31). The air EO level was not monitored routinely, however, peak concentrations of EO up to 200 p.p.m. were detected mainly when the sterilization chambers were open. Our results show a significant difference in urinary thioether excretion between the exposed and control groups (P less than 0.001). Sterilization workers seem to absorb significant quantities of EO. We feel that other alternative and more sensitive methods for detecting thioether metabolites of EO should be carried out to confirm our results. PMID- 1639878 TI - Inappropriate digoxin monitoring. AB - The digoxin therapeutic drug monitoring service was evaluated during a 7-week period at Leeds General Infirmary. Data were collected for 88 patients who had one or more assays performed. The requesting clinician was contacted for each assay, and a questionnaire completed. Results were assessed to determine the appropriateness of the assay request and the action taken following receipt of the result. During the assessment period, 113 serum digoxin assays were requested. Data were collected for 88 (78%) of these, of which 22 (25%) were considered to have met all the criteria for an appropriate assay request and subsequent action. A total of 66 (75%) serum digoxin assays were assessed as wasted. The digoxin therapeutic drug monitoring service is used inappropriately at Leeds General Infirmary. PMID- 1639879 TI - Lack of effect of codeine in the treatment of cough associated with acute upper respiratory tract infection. AB - Codeine is often used as a standard antitussive against which new antitussives are compared. However there is little information available about the effects of codeine on cough associated with upper respiratory tract infection. The present study investigated the effects of codeine syrup B.P. (30 mg/10 ml, q.d.s.) or syrup vehicle on cough frequency and the subjective severity of cough during a 3 h laboratory phase and a 4-day home phase of treatment. Cough frequency and subjective scores of cough severity were significantly decreased during the 3-h laboratory phase but at no time point was there a significant difference between the codeine- and placebo-treated groups. The results of the 4-day home phase diary were similar to those of the laboratory phase as at no time point was there a significant difference between the mean scores for the codeine- and placebo treated groups. The results indicate that codeine, either as a single 30-mg dose or in a total daily dose of 120 mg, is no more effective than the syrup vehicle in controlling cough associated with acute upper respiratory tract infection. PMID- 1639880 TI - Stability of mupirocin ointment (Bactroban) admixed with other proprietary dermatological products. AB - This study involved the mixing of 1:1 combinations of Bactroban (mupirocin) Ointment 2% with various cream, lotion, ointment, gel, solution and liquid soap formulations with storage at 37 degrees C for 60 days. The mixtures were assayed for mupirocin content at 0, 15, 30, 45 and 60 days using a high-pressure liquid chromatographic (HPLC) assay. At the time of preparation of these admixtures, Bactroban Ointment is chemically and physically compatible with all of the topical dermatological products studied except for Valisone lotion where a physical incompatibility is immediately observed. Admixtures of Hibiclens liquid soap or Lotrimin solution with Bactroban Ointment were stable throughout the entire 60-day study. Combinations of Lotrimin cream, Hytone cream, Valisone ointment or Vytone cream with Bactroban Ointment also retained chemical stability of mupirocin for the entire period even though two layers were observed and mixing was required to restore a physically homogenous mixture. Other Bactroban Ointment admixtures were found to be either chemically stable for mupirocin for periods less than 60 days or physically incompatible mixtures were observed upon storage. No conclusions were drawn from these studies concerning the efficacy or safety of any of these products when used in extemporaneously prepared combinations. PMID- 1639881 TI - Stability of captopril in some aqueous systems. AB - A stability-indicating high performance liquid chromatographic method has been proposed to quantify captopril. The method has been used to determine the stability of captopril in oral liquid dosage forms prepared from either commercially available tablets or powder. The dosage forms in water were more stable than when the vehicle was a syrup. Furthermore, the dosage form prepared using powder in water was more stable than when tablets were used. While the decomposition of captopril followed first-order equation when the dosage forms were prepared in syrup (in two of the three solutions studied), this equation was not followed when water was the vehicle. This is probably due to an uncontrolled factor, oxygen, because captopril is very sensitive to oxidation. Captopril solution prepared in water using tablets was stable for about 20 days when stored at 5 degrees C, and that prepared using powder in water was stable for about 27 days. One commercial syrup hastened the process of decomposition with an additional unidentified product of decomposition. PMID- 1639882 TI - The decomposition of phenylmercuric nitrate caused by disodium edetate in neomycin eye drops during the process of heat sterilization. AB - High-performance liquid chromatographic (HPLC) assays have been developed for phenylmercuric nitrate and mercuric ions in the presence of disodium edetate. Application of these methods to neomycin eye drops of the Pharmaceutical Codex and Australian Pharmaceutical Formulary, which contain both phenylmercuric nitrate and disodium edetate, show that edetate promotes approximately 20% decomposition of the phenylmercuric nitrate in the drops of the Pharmaceutical Codex but little in the drops of the Australian Pharmaceutical Formulary during sterilization by the recommended method. The reason for the stability of the organomercurial in the Australian product was determined as being due to the presence of sodium chloride in the formulation. PMID- 1639883 TI - [A new surgical method for chronic pancreatitis: Vankemmel's wirsungo sphincteroclasis (50 cases)]. AB - Since 1986, Vankemmel M. has been advocating, in case of severe chronic pancreatitis with dilatation, even slight, of the pancreatic duct without associated cavity formation, to carry out wirsungosphincteroclasis (W-SC): 50 cases. This original technique includes a short cephalic wirsungotomy followed by the removal of canal obstruction by transampullary wirsungoduodenal caliber restoration, then a temporary wirsungonasal drainage. This procedure has been associated to a biliodigestive anastomosis in 27 cases, including 25 cases in which a gallbladder loop was used. RESULTS: Only one patient (2%) who had already been treated with caudal splenopancreatectomy with pancreaticojejunal anastomosis and presented with portal thrombosis and compression of the common bile duct, died of mesentericointestinal infarction during the postoperative period. During the first month, no pancreatic fistula was noted but 3 patients were operated again: one at D3 to reposition the torn-off wirsungonasal drain, one for angiocholitis requiring a biliodigestive anastomosis, and the third one for acute intestinal obstruction. Later on, only 4 patients (8%) were operated on successfully (3rd, 16th, 20th, 33rd month) to complete the removal of canal obstruction. PMID- 1639884 TI - [Fatal hydatid pulmonary embolism during hepatectomy for hydatid cyst. Apropos of a case]. AB - Liver Hydatid cysts located close to the inferior vena cava and the sus-hepatic veins are known for their risk of rupture inside these veins. The authors report the case of a patient who died from massive pulmonary embolism during the surgical treatment (hepatectomy) of liver hydatid cysts. Diagnosis and treatment of these fistula are reviewed. PMID- 1639885 TI - [Splenosis after splenic rupture: a disease to be recognized]. AB - One case of peritoneal splenosis is reported. The diagnosis was established at surgery in a 17-year-old female patient presenting with dull abdominopelvic pain, who had undergone total splenectomy after a trauma ten years earlier. This autograft of splenic tissue must be known to be acknowledged, especially today, when the conservative treatment advocated for ruptures of the spleen may increase its incidence. The literature reports only about one hundred cases. The treatment only consists in removing the sole symptomatic nodules. PMID- 1639886 TI - [Problems posed by the inferior vena cava in liver transplantation]. AB - On the basis of a 200-case series, we report about the problems posed by the inferior vena cava for liver transplantation, and about the means implemented to solve these problems. Before hepatic transplantation, agenesia of the vena cava, which was encountered once, did not prevent grafting. During transplantation, the inferior vena cava posed problems due to its size or to the approach. These were solved using an extracorporeal venovenous shunt, which we advocate to systematically use for liver transplantation. Following transplantation, in addition to hemorrhages, the problems posed by the IVC included supra- or infrahepatic anastomotic stenoses (2 cases) and infrarenal, retrohepatic or suprahepatic thromboses (2 cases). Their repair again resorted to a venovenous shunt, for which we specify the strategy of use. PMID- 1639887 TI - [Bacterial endocarditis complicated by popliteal and mesenteric aneurysms]. AB - The authors report about one case of bacterial endocarditis complicated by fungal aneurysms in a superior mesenteric and a popliteal site. While the diagnosis was easy for the popliteal aneurysm, it was not so for the mesenteric aneurysm. Arteriography must have wide indications. The treatment of such aneurysms must always be medical, but surgical as well. The surgical tactics must be carefully discussed, and the restoration of vascular continuity with autologous venous material through an extra-anatomic course should be preferred. PMID- 1639888 TI - [Cancer of the urachus. A rare form of tumors of the bladder]. AB - Cancers of the middle umbilical fold are very infrequent, making up 0.1% to 0.7% of all bladder tumors. This type of tumor affects male subjects in 60% to 75% of cases, in the 5th or 6th decade of life. In more than 90% of all cases, the lesion is a mucosecretory adenocarcinoma developing from embryonic remains within the wall of the bladder and respecting the superficial urothelium of the bladder, which is affected only secondarily, contrary to what occurs in the other adenocarcinomas of the bladder. The pathogenesis remains controversial, especially the role of middle umbilical fold patency and of bladder carcinogens. The diagnosis is most often established late, because of a long clinical latency. It is mainly based on ultrasonography and computed tomography. Explorations of the bladder are useful only at an advanced stage. The prognosis is very poor, survival at 5 years ranging from 6.5% to 25% according to the authors. The treatment is mainly surgical. Only extensive exeresis with partial cystectomy extending to the peri- and supravesical environment, including the peritoneum and the umbilicus, and associated with pelvic lymphadenectomy may give some hope. Chemotherapy and radiation therapy, either alone or complementary, are disappointing. The prognosis may be improved only by an early diagnosis. PMID- 1639889 TI - [Necrotizing fasciitis: a medical and surgical emergency. Apropos of a case]. AB - We report about a 66-years-old obese and diabetic female patient, treated with anti-inflammatories for osteoarthritis of the hip and operated for varices of the lower limbs by a bilateral stripping of the internal saphenous veins, who presented with a mortal necrotizing fasciitis during the postoperative period. Necrotizing fasciitis is a severe, infrequent disease jeopardizing the vital prognosis, in which an appropriate and early treatment (medical, using antibiotics, and surgical by extensive debridement) can prevent a fatal outcome. The most often involved germs are streptococci (45%). The association of anaerobic and aerobic germs sometimes causes mixed cellulitis. The vital prognosis is always threatened by postoperative fasciitis. The mortality rate ranges from 50 to 75%, the main causes of death being a septic shock or pulmonary embolism. The functional prognosis of the surviving patients depends on the extent and quality of surgery. PMID- 1639890 TI - [Regional portal hypertension revealing malignant adrenal cortical carcinoma]. AB - The authors report a rare case of regional portal hypertension secondary to splenic vein obstruction by left adrenal carcinoma metastasis. They review the principal literature data concerning regional portal hypertension and adrenal cortical carcinoma. PMID- 1639891 TI - [Subtalar prosthesis. Operative technique and first results]. AB - Subtular arthrodesis is the only surgical procedure used in case of post traumatic arthrosis following fractures of the os calcis. The author proposes an original technique, which allows restoring the mobility of the hindfoot and suppressing pain: the subtalar prosthesis is described, as well as the surgical procedure. The short-term results for a series of five patients are very satisfactory. PMID- 1639892 TI - Assessment of the biotransformation of the cardiotonic agent piroximone by high performance liquid chromatography and gas chromatography-mass spectrometry. AB - 14C-labelled piroximone was administered to rats at a dose of 10 mg/kg body weight. Of the total radioactivity administered, 74.9 +/- 7.9% (n = 4) and 87.8 +/- 1.7 (n = 3) were recovered in the 8-h urine collection after oral and intravenous administration, respectively. Two major metabolites, M1 and M2, were detected in methanol extracts and accounted for 7.1 +/- 1.2% (n = 4) (M1) and 4.3 +/- 0.4% (n = 4) (M2) in response to oral administration and 5.7 +/- 0.8% (n = 3) (M1) and 6.7 +/- 2.0% (n = 3) (M2) in response to intravenous administration. In addition, three minor metabolites were detected; M3 and M4 in the 8-h urine collection and M5 in the 12-h urine collection. Separation of piroximone and metabolites was achieved by high-performance liquid chromatography on a C18 column by gradient elution with 0.05 M ammonium acetate (pH 7) using 0-60% methanol over 20 min at a flow-rate of 1 ml/min, followed by isocratic elution with 60% methanol for 10 min. M1 and M2 were isolated by fraction collection following the addition of 1 mM tetrabutylammonium acetate in the mobile phase. Between each injection a column re-equilibration time of 45 min was necessary to achieve optimum collection of M1 and M2 fractions. Gas chromatography-mass spectrometry of M1 provided evidence for a molecular structure consistent with isonicotinic acid methyl ester. Corroborative evidence for this identification was obtained by comparison with a synthetic standard. Isonicotinic acid is assumed to be the actual metabolite while esterification with methanol had occurred as a result of the work-up procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639893 TI - High-performance liquid chromatography of amino acids, peptides and proteins. CXV. Thermodynamic behaviour of peptides in reversed-phase chromatography. AB - The thermodynamic behaviour of three peptides, bombesin, beta-endorphin and glucagon, was studied under reversed-phase high-performance liquid chromatographic conditions. Experimental data related to the interactive surface contact area (S values) and solute affinity (log k0) were derived over a range of temperatures between 5 and 85 degrees C. These experimental conditions allowed changes in the secondary structure of the solute to be monitored. The influence of the nature of the stationary phase ligand on the relative conformational stability of the three peptides was analysed by acquiring data with n-octadecyl silica (C18) and n-butyl silica (C4) sorbents. Values for the relative changes in entropy and enthalpy associated with the interactive process were also determined. The results provide further insight into the factors involved with the stabilization of secondary structure and the mechanism of the interaction of peptides with hydrophobic surfaces. PMID- 1639894 TI - Direct determination of kallikrein by high-performance liquid chromatography. AB - A direct and specific identification of porcine pancreatic kallikrein by high performance hydrophobic chromatography is proposed; the minimum amount which can be injected is 2.5 U. An application to the quantitative determination of the enzyme by high-performance size-exclusion chromatography is reported; the method is precise with a mean coefficient of variation of 2.8% and the minimum amount which can be injected is 0.02 U of kallikrein. The results obtained with determinations in real biological samples (porcine pancreatic powder and human urine) are reported. The method is based on direct and specific chromatographic signals and does not destroy the biological activity of this enzyme. PMID- 1639895 TI - Isolation and characterization of alpha-glucosidase from Aspergillus niger. AB - alpha-Glucosidase is an enzyme widely used in biochemical analytical methods. Aspergillus niger was selected as a potential source for its production. Conditions for glucosidase production were optimized and the enzyme was isolated from the culture supernatant by dialysis and anion-exchange chromatography. The activity of the enzyme was determined by maltose hydrolysis to glucose, which was determined using a glucose-specific electrode or by high-performance liquid chromatography. The isolated enzyme was further characterized by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, substrate specificity and fast protein liquid chromatography. The Michaelis constant, optimal temperature and stability of the enzyme preparation were determined. PMID- 1639896 TI - Reversed-phase high-performance liquid chromatography-thermospray mass spectrometry of radiation-induced decomposition products of thymine and thymidine. AB - High-performance liquid chromatography-thermospray mass spectrometry was applied to the analysis of various radiation-induced decomposition products of thymidine including N-(2-deoxy-beta-D-erythro-pentofuranosyl)formamide and the various diastereomers of 5,6-dihydroxy-5,6-dihydrothymidine, 5-hydroxy-5,6 dihydrothymidine and 5,6-dihydrothymidine. This method combines high sensitivity and product resolution, rendering it particularly useful for monitoring the formation of radiation-induced base damage within DNA. PMID- 1639897 TI - Improved determination of individual molecular species of phosphatidylcholine in biological samples by high-performance liquid chromatography with internal standards. AB - Phosphatidylcholine isolated from samples of bile, liver and plasma was converted into 1,2-diradylglycerobenzoate molecular species by hydrolysis with phospholipase C and reaction with benzoic anhydride. Up to seventeen molecular species were separated and determined by reversed-phase high-performance liquid chromatography with detection at 230 nm. The major improvement introduced here was the use of distearoylphosphatidylcholine as the internal standard, which corrected the results for incomplete hydrolysis and benzoylation. Other improvements concerned the clean-up of benzoyl derivatives and the chromatographic separation. The analytical results obtained were validated by comparison with the results of either lipid phosphorus or gas chromatographic determinations. PMID- 1639898 TI - Determination of benzene metabolites in urine of mice by solid-phase extraction and high-performance liquid chromatography. AB - A method was developed for quantitative measurement of trans,trans-muconic acid, catechol, hydroquinone and phenol in urine. Hydrolysis of esterified and glucuronized phenolic compounds was effected by specific enzymes. The hydrolysed mixture was purified and separated by solid-phase extraction with an anion exchanger, followed by extraction with diethyl ether. By using a clean-up procedure the natural background from mouse urine could be reduced, so that the detection limit of the metabolites was in the range 3-60 mg/l. Optimization of the chromatographic conditions resulted in a short high-performance liquid chromatography analysis time. Phenol had the longest retention time of about 10 min. The clean-up procedure could also be used for phenylmercapturic acid, an additional benzene metabolite, but for sensitive high-performance liquid chromatographic detection of phenylmercapturic acid other conditions are necessary. PMID- 1639899 TI - High-performance liquid chromatographic determination of penicillin G, penicillin V and cloxacillin in beef and pork tissues. AB - The objective was to develop confirmatory high-performance liquid chromatographic methods for penicillin residues in animal tissues with detection limits of less than or equal to 10 ng/g. A previously described procedure was modified by using a larger sample size and isocratic analysis. Tissues (15 g) were blended with 45 ml of water and 20 ml of homogenate were mixed with 40 ml acetonitrile and filtered. The filtrate (30 ml) was mixed with 10 ml of 0.2 M H3PO4 and extracted with methylene chloride. The combined methylene chloride layers were mixed with acetonitrile and hexane, washed with two 4-ml portions of water and then extracted with four 1-ml portions of 0.01 M phosphate buffer (pH 7). The combined buffer extracts were concentrated to 1 ml under reduced pressure. Analysis was isocratic during 0.01 M phosphate buffer (pH 7)-acetonitrile with proportions 85:15 (penicillin G), 82:18 (penicillin V) or 78:22 (cloxacillin). A polystyrene divinylbenzene copolymer column, 150 x 4.6 mm I.D. (Polymer Labs. PLRP-S), was used with a flow-rate of 1 ml/min and detection at 210 nm. The presence of penicillins was confirmed by treating a duplicate sample with penicillinase. Recoveries were greater than 90% in most instances. Detection limits were 5 ng/g in muscle and higher in liver and kidney. The procedure is a simple and sensitive method for confirming the presence of penicillins in animal tissues. PMID- 1639900 TI - Determination of inositol polyphosphates from human T-lymphocyte cell lines by anion-exchange high-performance liquid chromatography and post-column derivatization. AB - The intracellular amounts of several inositol tris-, tetrakis- and pentakisphosphates and inositol hexakisphosphate were determined in resting and stimulated cells from human T-lymphocyte lines. The inositol polyphosphates were separated by anion-exchange high-performance liquid chromatography and were detected on-line by a recently developed post-column dye system. In the human T lymphocyte cell line Jurkat, basal intracellular concentrations ranged between 25 +/- 10 pmol per 10(9) cells for inositol 1,4,5-trisphosphate to 6380 +/- 355 pmol per 10(9) cells for inositol hexakisphosphate. Similar basal concentrations were observed in the human T-lymphocyte cell line HPB.ALL, with the exception that inositol hexakisphosphate was approximately 665 +/- 10 pmol per 10(9) cells. Stimulation of the human T-lymphocyte cell line Jurkat via the T-cell receptor by a monoclonal antibody directed against the T-cell receptor-CD3 complex induced time-dependent changes in the intracellular concentrations of multiple inositol polyphosphate isomers, including inositol 1,3,4-trisphosphate, inositol 1,3,4,5 tetrakisphosphate, inositol 1,3,4,6-tetrakisphosphate, an as yet unidentified inositol tetrakisphosphate isomer, inositol 1,3,4,5,6-pentakisphosphate, inositol 1,2,3,4,6-pentakisphosphate and DL-inositol 1,2,4,5,6-pentakisphosphate. Inositol 1,4,5-trisphosphate increased only transiently after 5 min, whereas DL-inositol 1,4,5,6-tetrakisphosphate (determined as the enantiomeric mixture) increased after 20 min. PMID- 1639901 TI - Separation of flavonol-2-O-glycosides from Calendula officinalis and Sambucus nigra by high-performance liquid and micellar electrokinetic capillary chromatography. AB - Calendula officinalis and Sambucus nigra flowers were analysed by reversed-phase high-performance liquid chromatography (RP-HPLC) and micellar electrokinetic capillary chromatography (MECC). RP-HPLC was performed on C8 Aquapore RP 300 columns with eluents containing 2-propanol and tetrahydrofuran. MECC was carried out on a 72-cm fused-silica capillary using sodium dodecyl sulphate and sodium borate (pH 8.3) as the running buffer. The results obtained by these techniques are compared. PMID- 1639902 TI - High-performance liquid chromatographic method with fluorescence detection for the determination of total homocyst(e)ine in plasma. AB - A high-performance liquid chromatographic method for the determination of total plasma homocyst(e)ine [H(e)] after reduction with sodium tetrahydroborate and precolumn derivatization with o-phthaldialdehyde is described. The analyses, carried out on a reversed-phase C18 column, were based on spectrofluorimetric detection. The sensitivity was 1 pmol per injection and the intra- and inter assay relative standard deviations were 1.8% and 5%, respectively. The plasma H(e) concentration determined in 40 healthy volunteers (20-60 years old) was 12.4 +/- 2.9 microM (mean +/- S.D.), in good agreement with reference values. PMID- 1639903 TI - Determination of catecholamines in urine by liquid chromatography and electrochemical detection after on-line sample purification on immobilized boronic acid. AB - Norepinephrine, epinephrine and dopamine in urine were measured by an automated liquid chromatographic method. After sample purification on a column containing silica-immobilized boronic acid, which showed great affinity for catecholamines at neutral pH, the catecholamines were eluted by backflushing with an acidic mobile phase and transferred to a cation exchanger for separation. Detection was performed electrochemically and the relative standard deviation was 2% for the analysis of endogenous concentrations in human urine. PMID- 1639904 TI - Determination of cinnamic acid and paeoniflorin in traditional Chinese medicinal preparations by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method for the determination of cinnamic acid in Cinnamomi ramulus and paeoniflorin in Paeoniae radix was established. The samples were separated by a LiChrospher RP-18 column with water acetonitrile-methanolacetic acid (61:34:5:0.1 or 80:15:5:0.1, v/v) as the mobile phase at a flow-rate of 1.0 ml/min. Cinnamic acid and paeoniflorin were determined by UV detection at 280 and 250 nm, respectively. The method was applied to determine the optimum conditions for the extraction of the traditional Chinese medicinal preparation Huang Chi Chien Chung Tong, which contains Cinnamomi ramulus and Paeoniae radix. The results indicate that the best extraction conditions involved the use of an ultrasonic bath at 60 degrees C for 30 min. In this experiment, butyl paraben and methyl paraben were used as the internal standards for cinnamic acid and paeoniflorin, respectively. A good and reproducible separation of cinnamic acid and paeoniflorin was obtained within 15 min. The method was also applicable to other preparations that contain Cinnamomi ramulus and Paeoniae radix such as Guey Chi Chia Long Ku Muu Li Tong, Kuei Chi Chien Chung Tong and Tang Kuei Chien Chung Tong. PMID- 1639905 TI - Use of high-performance liquid chromatographic peak deconvolution and peak labelling to identify antiparasitic components in plant extracts. AB - Artemisia absynthium L. is a commonly used medicinal plant for parasitic diseases all over the world. By means of high-performance liquid chromatography with diode array detection and the PU6100 solvent optimization system, two sesquiterpene lactones, alpha-santonin and ketopelenolid-A, were tentatively identified in methanolic extracts of this plant. alpha-Santonin is a well known antiparasitic compound and could be one of the active principles of this plant species. Reconstructed spectra are potentially useful in scanning a complex chromatogram for pharmacologically active compounds. PMID- 1639906 TI - Automated high-performance liquid chromatographic method for the determination of rifampicin in plasma. AB - Due to the unstable nature of rifampicin, a rapid automated high-performance liquid chromatographic method had to be developed for the analysis of a large number of plasma samples generated during a bioavailability trial. Extraction and injection of the samples were automatically done by a sample preparation system using C2, 100 mg Bond Elut extraction columns. The extracts were chromatographed on a 4-microns reversed-phase C18 column with a citrate buffer and acetonitrile as mobile phase. The analytes were detected at 342 nm. Calibration curves were linear to at least 20 micrograms/ml and the limit of quantification was 0.16 micrograms/ml. PMID- 1639907 TI - Improved high-performance liquid chromatographic method for the determination of coenzyme Q10 in plasma. AB - Coenzyme (Co) Q10 was dissociated from lipoproteins in plasma by treatment with methanol and extraction with n-hexane. Subsequent clean-up on silica gel and C18 solid-phase extraction cartridges with complete recovery (99 +/- 1.2%) produced a clean extract. High-performance liquid chromatographic (HPLC) separation was performed on a C18 reversed-phase column. Three simple, rapid procedures are presented: HPLC with final UV (275 nm) detection, a microanalysis utilizing a three-electrode electrochemical detector and a microanalysis with column switching HPLC and electrochemical detection. The methods correlate very well with classical ethanol-n-hexane extraction with UV detection. The identity and purity of the Co Q10 peak were investigated and the resulting methods were concluded to be suitable for total plasma Co Q10 determination. The average level in healthy subjects was 0.80 +/- 0.20 mg/l; the minimum detectable Co Q10 plasma level was 0.05 and 0.005 mg/l for UV and electrochemical detection, respectively. The methods were applied to many samples and the plasma Co Q10 reference values for healthy subjects, athletes, hyperthyroid, hypothyroid and hypercholesterolaemic patients are given. PMID- 1639908 TI - High-performance liquid chromatographic analysis of FCE 24304 (6-methylenandrosta 1,4-diene-3,17-dione) and FCE 24928 (4-aminoandrosta-1,4,6-triene-3,17-dione), two new aromatase inhibitors. AB - The cytochrome P-450-dependent aromatase enzyme plays an important role in hormone-dependent diseases. Many products that inhibit this type of enzyme were obtained: FCE 24304 (I) and FCE 24928 (II) proved to possess remarkable activity and are presently under development. Compounds I and II and their synthetic intermediates are analyzed by means of a high-performance liquid chromatographic method, affording rapid and efficient separation, good resolution and identification of all the examined compounds. The linearity, specificity, sensitivity, precision and accuracy for the method are also provided. PMID- 1639909 TI - Determination of substituted purines in body fluids by micellar electrokinetic capillary chromatography with direct sample injection. AB - Many substituted purines (theobromine, caffeine, paraxanthine, theophylline and uric acid, as well as other methylated xanthines and uric acids) can easily be separated and analysed in one run using micellar electrokinetic capillary chromatography with a boratephosphate buffer containing 75 mM sodium dodecyl sulphate (pH approximately 9). Serum, saliva and urine samples collected after the self-administration of caffeine and serum samples from patients receiving theophylline or caffeine pharmacotherapy were screened for substituted purines. The data presented show the ease of using on-column multi-wavelength detection for investigating the feasibility of direct sample application, the characterization of sample pretreatment procedures and peak confirmation by comparing absorption spectra. It is shown that the determination of purines in serum and saliva samples, including therapeutic concentrations of caffeine and theophylline, can be accomplished without any sample pretreatment, whereas sample extraction is required for the determination of purines in urine. Quantitative data for the determination of micromolar amounts of theophylline (samples from adult patients) and caffeine (samples from infants born prematurely) in serum samples compared well with data obtained by non-isotopic immunoassays. Micellar electrokinetic capillary chromatography with the direct injection of serum or saliva samples requires only microlitre volumes of sample and several different compounds can be determined within a few minutes. PMID- 1639910 TI - Prediction of migration behavior of oligonucleotides in capillary gel electrophoresis. AB - The influence of the primary structure (base composition) on the electrophoretic migration properties of single-stranded oligodeoxyribonucleotides in capillary polyacrylamide gel electrophoresis was investigated using homo- and heterooligomers under denaturing and non-denaturing conditions. Homooligodeoxyribonucleotides of equal chain lengths but of different base composition showed significant differences in mobility. In addition, the migration properties of heterooligomers were found to be highly dependent on their base composition. A simple equation is presented for predicting relative migration times using denaturing and non-denaturing polyacrylamide capillary gel electrophoresis. Orange-G was used as an internal standard and as the basis of the relative migration time calculations. Examples are presented using homo- and heterooligomers in the 10-20-mer range to show the correlation of the primary structure and their predicted and observed migration rates. PMID- 1639911 TI - Simple reversed-phase high-performance liquid chromatographic method for 13-cis retinoic acid in serum. AB - An isocratic reversed-phase high-performance liquid chromatographic method for the analysis of 13-cis-retinoic acid in serum is developed. Sample preparation includes deproteination with acetonitrile-perchloric acid-acetic acid followed by centrifugation. 9-Methylanthracene is used as the internal standard. Chromatographic separation is achieved on a C18 column (Zorbax) using an acetonitrile-aqueous 0.5% acetic acid (85:15, v/v) eluent containing 0.05% (w/v) sodium hexanesulfonate. The limit of detection is 12 ng/ml in serum, using 0.5 ml samples. Quantitative recoveries and excellent intra-day and inter-day precision are reported. PMID- 1639912 TI - Stability studies with a high-performance liquid chromatographic method for the determination of a new anthracycline analogue, 3'-deamino-3'-[2-(S)-methoxy-4 morpholino)doxorubicin (FCE 23762), in the final drug formulation. AB - A high-performance liquid chromatographic method was studied to optimize the separation of FCE 23762, a new antitumour agent, from both synthetic impurities and degradation products having very similar molecular structures. The main problems faced in the analytical method development using the most common reversed-phase columns available arose from the presence of analytical peaks with poor symmetry, a long analysis time and the separation between FCE 23762 and its R-isomer, which was often unsuitable for the correct determination of the drug substance. The use of a new stationary phase, Zorbax Rx-C8, together with a suitable mobile phase resulted in a good separation between the diastereomers, with satisfactory peak symmetry and run time. The method permitted the study of the stability of the drug substance in formulations for clinical trials. PMID- 1639913 TI - Determination of the catechol-O-methyltransferase inhibitor Ro 40-7592 in human plasma by high-performance liquid chromatography with coulometric detection. AB - A sensitive and specific high-performance liquid chromatographic method has been developed to measure the catechol-O-methyl-transferase (COMT) inhibitor 3,4 dihydroxy-4'-methyl-5-nitrobenzophenone (Ro 40-7592) in human plasma. The compound and the internal standard were extracted from plasma at pH 2 with n butyl chloride-ethyl acetate (95:5, v/v). The extract was chromatographed on a reversed-phase column (Hypersil ODS, 5 microns) using a mixture of phosphate buffer (0.05 M, pH 2), methanol and tetrahydrofuran (45:55:5, v/v/v) as the mobile phase. Long-retained components were removed from the system by means of a simple column-switching system. Quantification of the catechol-O methyltransferase inhibitor was performed by means of coulometric detection (0.1 V). The limit of quantification was about 1 ng/ml, using a 1-ml specimen of plasma. The recovery from human plasma was greater than 88%. The mean inter-assay precision was 5.3% in the range 2.5-1000 ng/ml. Linearity of the standard curve was obtained in the concentration range 2.5-500 ng/ml. The catechol-O methyltransferase inhibitor was stable in human plasma when stored for six months at -20 degrees C and for 24 h at room temperature. The practicability of the new method was demonstrated by the analysis of more than 400 plasma samples from a tolerance study performed in human volunteers. PMID- 1639914 TI - Determination of Zy 17617B in plasma by solid-phase extraction and liquid chromatography with automated pre-column exchange. AB - An automated chromatographic system, combining solid-phase extraction and automated pre-column exchange, is described for the routine determination of Zy 17617B at the pmol/ml level in human plasma. The sample extraction and elution onto the analytical column were performed automatically and concomitantly using a conventional liquid chromatographic apparatus equipped with a Merck OSP-2 on-line sample preparator. Validation data demonstrate the reliability of the method. PMID- 1639915 TI - Determination of (S)-(-)-cathinone and its metabolites (R,S)-(-)-norephedrine and (R,R)-(-)-norpseudoephedrine in urine by high-performance liquid chromatography with photodiode-array detection. AB - A high-performance liquid chromatographic (HPLC) procedure with photodiode-array detection (DAD) is described for the determination of (S)-(-)-cathinone (S-CA) and its metabolites (R,S)-(-)-norephedrine (R-NE) and (R,R)-(-) norpseudoephedrine (R-NPE) in urine. Extraction and clean-up of 1-ml urine samples were performed on a cyano-bonded solid-phase column using (+/-) amphetamine as internal standard. The concentrated extracts were separated on a 3 microns ODS-1 column with acetonitrile-water-phosphoric acid-hexylamine as the mobile phase. Peak detection was done at 192 nm. The detection limits for S-CA and R-NE/R-NPE in urine were 50 and 25 ng/ml, respectively. The differentiation of the enantiomers of cathinone and norephedrine was achieved by derivatization with (S)-(-)-1-phenylethyl isocyanate to the corresponding diastereomers followed by HPLC-DAD on a 5-microns normal-phase column. The R and S enantiomers of norpseudoephedrine were determined by gas chromatography-mass spectrometry after on-column derivatization with (S)-(-)-N-trifluoroacetylprolyl chloride. Following a single oral dose of 0.5 mg/kg of S-CA, the concentrations found in urine ranged from 0.2 to 3.8 micrograms/ml of S-CA, from 7.2 to 46.0 micrograms/ml of R-NE and from 0.5 to 2.5 micrograms/ml of R-NPE. PMID- 1639916 TI - Determination of psychotropic phenylalkylamine derivatives in biological matrices by high-performance liquid chromatography with photodiode-array detection. AB - Several procedures using high-performance liquid chromatography with photodiode array detection have been developed to create phytochemical and toxicological profiles of phenylalkylamine derivatives in biological samples (e.g. plant materials and urine). Mescaline-containing cactus samples were extracted with basic methanol, using methoxamine as internal standard; the extraction and clean up of urine samples were performed on cation-exchange solid-phase extraction columns. The extracts were separated on a 3-micron ODS column with acetonitrile water-phosphoric acid-hexylamine as the mobile phase. Peak detection was performed at 198 or 205 nm; peak identity and homogeneity were ascertained by on line scanning of the UV spectra from 190 to 300 nm. The detection limit of phenylalkylamine derivatives in urine and cactus material was 0.026-0.056 micrograms/ml and 0.04 micrograms/mg, respectively. Following a single oral dose of 1.7 mg/kg methylenedioxymethylamphetamine (MDMA) the concentrations found in urine ranged from 1.48 to 5.05 micrograms/ml MDMA and 0.07-0.90 micrograms/ml methylenedioxyamphetamine (a metabolite of MDMA). The mescaline content of the cactus Trichocereus pachanoi varied between 1.09 and 23.75 micrograms/mg. PMID- 1639917 TI - High-performance liquid chromatographic determination of alpha-tocopheryl nicotinate in cosmetic preparations. AB - alpha-Tocopheryl nicotinate (alpha-TN) accelerates blood circulation and stimulates hair follicle cells, hence it is an active ingredient in a broad range of cosmetic products. A reversed-phase high-performance liquid chromatographic method was developed to determine alpha-TN in cosmetic preparations with alpha tocopheryl acetate as internal standard. The method was found to be rapid, precise and specific. PMID- 1639918 TI - Rapid determination of amino acids by high-performance liquid chromatography: release of amino acids by perfused rat liver. AB - Perfused rat liver can be considered as one of the most suitable ex vivo models for studies of liver metabolism. To assess the possible effect of L-carnitine and some of its acyl esters on proteolysis in the rat liver, the amino acid derivatization and high-performance liquid chromatographic separation of Tapuhi et al. [Anal. Biochem., 115 (1981) 123] was modified. PMID- 1639919 TI - Selective adsorption of immunoglobulins and glucosylated proteins on phenylboronate-agarose. AB - Aminophenylboronate-substituted agarose in 20 mM N-2-hydroxyethylpiperazine-N'-2 ethanesulphonic acid, pH 8.5, selectively adsorbs immunoglobulins and complement factors C3 and C4 from human serum. The selectivity of binding is strongly influenced by the presence of magnesium chloride in the sample buffer. Adsorbed immunoglobulins are quantitatively eluted by sorbitol, but only partially by ethylene glycol or methylcellosolve. Aniline-agarose of a similar degree of substitution shows only weak adsorption of serum proteins under similar experimental conditions, thus indicating the important contribution of the boronate moiety to this interaction. Immunoglobulin adsorption seems not to be due to the cis-diol complexation used extensively for the chromatographic determination of non-enzymatically glucosylated proteins. Hydrophobic and pi-pi interactions with the aromatic structure of the ligand seem also to contribute to protein binding. The behaviour of aminophenylboronate-liganded agarose is, in some respects, rather similar to that of the so-called "thiophilic adsorbents". PMID- 1639921 TI - Synthetic metal-binding protein surface domains for metal ion-dependent interaction chromatography. I. Analysis of bound metal ions by matrix-assisted UV laser desorption time-of-flight mass spectrometry. AB - To extend the analytical capabilities of immobilized metal ion affinity chromatography (IMAC) for evaluation of biologically relevant peptide-metal ion interactions, we have prepared synthetic peptides representing metal-binding protein surface domains from the human plasma metal transport protein known as histidine-rich glycoprotein (HRG). Three synthetic peptides, representing multiples of a 5-residue repeat sequence (Gly-His-His-Pro-His) from within the histidine- and proline-rich region of the C-terminal domain were prepared. Prior to immobilization, the synthetic peptides were evaluated for identity and sample homogeneity by matrix-assisted UV laser desorption time-of-flight mass spectrometry (LDTOF-MS), a method developed recently for the mass determination of high-molecular-mass biopolymers. 2,5-Dihydroxybenzoic acid was evaluated as a matrix to facilitate the laser desorption and ionization of intact peptides and was found to be ideally suited for determinations of mass within the low-mass region of interest (641.7 to 1772.8 dalton). We observed minimal chemical noise from photochemically generated peptide-matrix adduct signals, clustering, and multiply-charged peptide species. Peptides with bound sodium and potassium ions were observed; however, these signal intensities were reduced by immersion of the sample probe tip in water. Mixtures of the three different synthetic peptides were also evaluated by LDTOF-MS after their elution through a special immobilized peptide-metal ion column designed to investigate metal ion transfer. We found LDTOF-MS to be a useful new method to verify the presence of peptide-bound metal ions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639920 TI - Immobilized hemoglobin in the purification of hemoglobin-based oxygen carriers. AB - Chemically modified hemoglobins can be used as oxygen carriers in cell-free fluids provided that they have a low oxygen affinity and are stable towards dissociation into subunits. The latter species are undesirable because they are filtered rapidly through the kidneys, have renal toxicity and are characterized by a high oxygen affinity. A most important step in the preparation of hemoglobin based oxygen carriers is therefore their purification from any dissociable material. Hemoglobin immobilized as alpha beta dimers on Sepharose lends itself naturally to this purpose as it is able to interact in a specific and reversible way with soluble alpha beta dimers. Hemoglobin affinity columns are very effective in the purification of cross-linked and pseudo-cross-linked human and bovine hemoglobin. The applicability of the technique is enhanced by the ease with which alpha beta dimers from different species cross-interact to yield hybrid alpha 2 beta 2 tetramers. It is shown that hemoglobin affinity columns may provide analytical information on the cross-linking reaction itself. PMID- 1639922 TI - Synthetic metal-binding protein surface domains for metal ion-dependent interaction chromatography. II. Immobilization of synthetic metal-binding peptides from metal ion transport proteins as model bioactive protein surface domains. AB - This preliminary investigation tests the premise that biologically relevant (1) peptide-metal ion interactions, and (2) metal ion-dependent macromolecular recognition events (e.g., peptide-peptide interactions) may be modeled by biomimetic affinity chromatography. Divinylsulfone-activated agarose (6%) was used to immobilize three different synthetic peptides representing metal-binding protein surface domains from the human plasma metal transport protein histidine rich glycoprotein (HRG). The synthetic peptides represented 1-3 multiple repeat units of the 5-residue sequence (Gly-His-His-Pro-His) found in the C-terminal of HRG. By frontal analyses, immobilized HRG peptides of the type (GHHPH)nG, where n = 1-3, were each found to have a similar binding capacity for both Cu(II) ions and Zn(II) ions (31-38 mumol/ml gel). The metal ion-dependent interaction of a variety of model peptides with each of the immobilized HRG peptide affinity columns demonstrated differences in selectivity despite the similar internal sequence homology and metal ion binding capacity. The immobilized 11-residue HRG peptide was loaded with Cu(II) ions and used to demonstrate selective adsorption and isolation of proteins from human plasma. These results suggest that immobilized metal-binding peptides selected from known solvent-exposed protein surface metal-binding domains may be useful model systems to evaluate the specificity of biologically relevant metal ion-dependent interaction and transfer events in vitro. PMID- 1639923 TI - Production, purification and characterization of recombinant human interferon gamma. AB - An essentially three-step chromatographic purification procedure, i.e., ion exchange, immobilized metal ion affinity and size-exclusion chromatography, is described for the purification to homogeneity of recombinant human interferon gamma (rhIFN-gamma) from the inclusion bodies produced in genetically transformed Escherichia coli cells. Batchwise adsorption of the cloudy solution of renatured rhIFN-gamma obviated the need for high-speed centrifugation to clarify the suspension. This step effectively removed about 70% of extraneous protein impurities. The established purification process is reproducible and leads to a total recovery of 32%. Pilot-scale processing of E. coli cells grown in a 30-l fermentor gave about 70 mg of a homogeneous preparation of rhIFN-gamma. The specific biological activity of purified rhIFN-gamma is ca. 3.4 x 10(7) I.U./mg protein, which is comparable to that of its natural counterpart. It is basic protein (pI greater than pH 9) with a monomer relative molecular mass of 15,000. It behaves, however, as a dimer on size-exclusion chromatography. Its partial NH2 terminal sequence is identical with that established for the rhIFN-gamma. However, its amino acid composition and its relative molecular mass (15,067 as determined by electrospray mass spectrometry) indicate that the purified protein is a truncated form lacking fifteen amino acid residues from its carboxyl terminal side. This modification does not seem to have any adverse effect on its biological potency. The levels of DNA, bacterial endotoxins and Ni(II) ions in the final product were determined. PMID- 1639925 TI - Isolation and characterization of catalase from Penicillium chrysogenum. AB - Catalase from a crude preparation of Penicillium chrysogenum was isolated in a single chromatographic step by immobilized metal ion affinity chromatography (IMAC) on Cu(II)-Chelating Sepharose Fast Flow. A chromatographically and electrophoretically homogeneous enzyme was obtained in 89% yield. IMAC was found to be superior to ion-exchange, hydrophobic interaction, size-exclusion and concanavalin A affinity chromatography. Analytical and preparative chromatography gave essentially the same chromatograms. Isoelectric point, molecular weight (by ultracentrifugation), amino acid composition, carbohydrate content and subunit organization were determined. The apparent Michaelis-Menten constant, KM, and the azide competitor constant, Ki, were calculated and found to be 59 microM and 6.1 microM, respectively. PMID- 1639924 TI - Affinity chromatographic separation of gonadotropic hormone agonist and antagonist antibodies. Implications for structure, immunological and biological properties of glycoproteins. AB - Gonadotropic hormones which have lost peripheral sugar residues in their oligosaccharide chains display antagonistic properties and produce antibodies that fail to recognize the fully glycosylated hormone (agonist form). These polyclonal antibodies were separated by successive affinity chromatography on divinylsulfonyl-Sepharose coupled agonist and antagonist columns. The immunoglobulin G fraction from the agonist affinity columns recognizes both free agonist and antagonist in solution radioimmunoassays and also when these hormone forms are bound to receptors on gonadal cells. However, antagonist-specific antibodies recognize only the free antagonist in solution but not when it is receptor bound, implying that the conformation of the receptor-bound antagonist is different from that of the agonist. Affinity-purified antibodies against the different forms are useful in analyzing immunological and biological properties of the hormones. The studies with these glycosylated hormones serve as a useful model for other glycoproteins of pharmaceutical value. PMID- 1639926 TI - Model studies on iron(III) ion affinity chromatography. II. Interaction of immobilized iron(III) ions with phosphorylated amino acids, peptides and proteins. AB - The chromatographic behaviour of phosphoamino acids, phosphopeptides and phosphoproteins and their non-phosphorylated counterparts was studied on Fe(III) Chelating Sepharose and Fe(III)-Chelating Superose. The phosphorylated compounds, in contrast to their non-phosphorylated or dephosphorylated counterparts, adsorb to immobilized iron(III) ions at pH 5.5 and can be desorbed by an increase in pH. Phosphoamino acids were eluted at pH 6.5-6.7, whereas monophosphopeptides and phosphoprotamine eluted in the pH range 6.9-7.5. Molecules possessing clusters(s) of carboxylic groups are weakly retained (gamma-carboxyglutamic acid, Ala-Ser Glu5) or bound (polyglutamic acid, beta-casein) to the immobilized iron(III) ions at pH 5.5. Dephosphorylated beta-casein was desorbed at pH 7.0, whereas for elution of native (non-dephosphorylated) beta-casein, phosphate buffer of pH 7.7 was required. The homopolymer of polyglutamic acid was desorbed in the pH range 6.0-6.3, whereas copolymers of glutamic acid and tyrosine require pH 7.0-7.3 or even phosphate buffer at pH 7.7 for elution. PMID- 1639927 TI - Interaction of immunoglobulin G with immobilized histidine: mechanistic and kinetic aspects. AB - A systematic investigation of coupling methods for and the chemistry and chromatographic parameters of immunoglobulin gamma (IgG) adsorption to histidine- and imidazole-coupled Sepharose gels was undertaken in order to elucidate the interactions involved in the mechanism of recognition between IgG and the immobilized histidine. The effects of pH, salt and temperature effects indicated an ion-pairing mechanism, rather than a mechanism based on the net charge of the protein (IgG), but with some localized complementary charges recognizing the unprotonated imidazole nitrogen. The effects of the addition of ethylene glycol and urea indicated the involvement of hydrogen bonding between the ligand and the protein. The immobilized histidine binds to the Fc fragment of IgG with a fairly low affinity, in a way similar to the N-terminum of protein A binding to the Fc fragment of IgG. The kinetic parameters of the chromatographic system indicated a good capacity but a low adsorption rate constant. PMID- 1639928 TI - Adsorption behavior of milk proteins on polystyrene latex. A study based on sedimentation field-flow fractionation and dynamic light scattering. AB - Sedimentation field-flow fractionation (SdFFF) has been used to characterize the adsorption of the proteins beta-casein (BCN) or beta-lactoglobulin (BLG) on colloidal polystyrene latices; this system was used to model hydrophobic interactions between the proteins and the surfaces of fat droplets in protein stabilized emulsions. It was found that the SdFFF technique could determine directly the surface concentrations of BCN and BLG irreversibly adsorbed to the latex surface, provided care was taken to maintain the ionic strength of the carrier at a level which suppressed particle-wall repulsion in the separation channel. The measured surface concentrations were similar for the two proteins (about 1 mg/m2), and this was verified by quantitative amino acid analysis. These concentrations were smaller than those found in depletion studies (3 and 4 mg/m2 respectively for BCN and BLG), in which loosely associated protein may have been included in the determinations. The thickness of the adsorbed layers was determined in situ by dynamic light scattering and was found to differ significantly for the two proteins (up to 15 nm for BCN vs. 2-3 nm for BLG). The implication of these findings in terms of different surface arrangements of the two proteins is discussed. PMID- 1639929 TI - Recycling isoelectric focusing: use of simple buffers. AB - Using the recycling free-flow focusing (RF3) apparatus, we have demonstrated that single ampholytes can be utilized to establish very stable pH regions, separating all proteins into three groups: a sharply resolved zone of proteins isoelectric at the prevailing pH, this "pH window" being bracketed by zones of more acidic and/or basic proteins. The ampholytes used are either amino acids or their dipeptides and other derivatives. Where necessary, because of lack of an ampholyte with the required pH, a binary mixture of ampholytes can be utilized. The closer their isoelectric points (pI), the narrower will be the pH window, i.e., the sharper the resolution of the bracketed proteins. This method overcomes the necessity of using ill-defined commercial carrier ampholytes, such as Ampholine, for preparative isoelectric focusing. It is recommended that the ampholytes be utilized at relatively high concentration, 100mM or higher, this contributing to pH stability and minimizing protein precipitation. PMID- 1639930 TI - Analysis of food additives by ion-pairing electrokinetic chromatography. AB - A mixture of food additives is separated using ion-pairing electrokinetic chromatography with on-column ultraviolet detection at 190 nm. Tetrabutyl ammonium hydrogen sulfate (TBA) is used as modifier. The effect of the concentration of TBA on the migration behavior of the solutes is investigated. This method is used for the determination of the amount of additives in food samples. The percent relative standard deviation (%RSD) for the migration time is found to be less than 0.9% and that of the peak area is less than 2.5%. PMID- 1639931 TI - Clinical review 36: Cardiovascular manifestations of endocrine disease. PMID- 1639932 TI - Non-thyrotropin-dependent thyroid secretion. PMID- 1639933 TI - Levothyroxine dose requirements for thyrotropin suppression in the treatment of differentiated thyroid cancer. AB - We have compared the dose of levothyroxine (L-T4) required to suppress serum TSH to given levels in two clinical groups: 1) 44 patients with thyroid cancer whose thyroid glands had been ablated by surgical thyroidectomy and 131I treatment, and 2) 113 patients with thyroidal failure due either to spontaneous primary hypothyroidism (31 patients) or after 131I treatment for Graves' hyperthyroidism (82 patients). The dose of L-T4 needed to attain serum TSH levels in the euthyroid range (0.5-6.2 microU/mL) was significantly greater (P less than 0.01) in patients with thyroid cancer (2.11 micrograms/kg.day) than in the patients with primary hypothyroidism associated with nonmalignant disease (1.63 micrograms/kg.day). Similarly, patients with thyroid cancer required a higher dose of L-T4 to suppress serum TSH to a given subnormal level. These findings suggest that the secretion of hormone from residual thyroid tissue in patients who have not been subjected to near-total thyroid ablation contributes substantially to the circulating levels of serum T4 and T3. We, therefore, infer that residual thyroidal secretion in the patients with hypothyroidism due to benign causes is relatively independent of TSH stimulation. Further subdivision of patients with benign hypothyroidism revealed that patients with Graves' who developed hypothyroidism after 131I treatment showed a lower mean dose requirement than patients with spontaneous hypothyroidism. This raises the possibility that continued secretion of thyroid-stimulating immunoglobulin in such patients might account for the lower dose requirement in the combined group with hypothyroidism. Our studies also have allowed us to make serial observations in 4 patients with thyroid cancer who exhibited elevated levels of serum thyroglobulin. In this limited series, maximal suppression of serum thyroglobulin was produced by doses of L-T4, which reduced circulating TSH to 0.4 mU/L. PMID- 1639934 TI - Effects of low-protein diets on protein metabolism in insulin-dependent diabetes mellitus patients with early nephropathy. AB - The dietary protein requirements of patients with insulin-dependent diabetes mellitus (IDDM) are unknown. We studied the metabolic adaptation of IDDM patients with early nephropathy to therapeutic, low-protein diets. Six patients were studied at baseline and following 1 and 12 weeks of consuming 0.6 g/kg-1 ideal body weight.day-1 protein. Outcome variables included quadriceps muscle strength, body composition, nitrogen balance, and estimates of whole body protein turnover using an infusion of L-[1-13C]leucine. All subjects experienced decreased muscle strength (6.6% decline in maximal torque, P = 0.05) and increased body fatness (11% increase in fat mass, P = 0.03) with no change in total body weight. This was accompanied by an initial 40% decrease in the rate of whole-body leucine oxidation after 1 week of dietary restriction which returned almost to baseline rates by 12 weeks (P less than 0.001, 1 week vs. 12 weeks). Nitrogen balance remained negative throughout the period of protein restriction. We conclude that IDDM subjects with early nephropathy experience protein undernutrition during the first 3 months of the dietary protein restriction currently recommended for the treatment of nephropathy. This may result, in part, from an inability to conserve essential amino acids from oxidative loss over the time period of the study. PMID- 1639935 TI - Peculiar distribution of adipose tissue in patients with congenital generalized lipodystrophy. AB - Congenital generalized lipodystrophy (CGL) is a rare genetic disease with extreme paucity of fat from birth which is believed to be generalized, involving the whole body. Affected patients are characterized by severe insulin resistance. Sites of adipose tissue distribution in patients with CGL have not been studied systematically. Therefore, the fat distribution in three women (17-20 yr old) with CGL was investigated. Determination of body composition by underwater volume displacement suggested the complete absence of body fat (range, -3 to -7%; normal, 15-25%). Whole body magnetic resonance imaging, however, detected fat in particular anatomical sites, namely in orbits, palms and soles, and periarticular and epidural regions. Some fat was also localized in the tongue, breasts, vulva, and buccal area. Fat in other subcutaneous areas, intraabdominal and intrathoracic regions, and bone marrow was essentially absent. Thus, patients with CGL do not have a complete absence of body fat; of interest, fat is present in those sites where adipose tissue may be serving mainly a mechanical function. Patients with CGL, therefore, provided a unique opportunity to identify the various sites of localization of "mechanical" adipose tissue in the human body. Our study suggests that the genetic defect in CGL results in poor growth and development of metabolically active adipose tissue, whereas mechanical adipose tissue is well preserved. PMID- 1639936 TI - Studies in a kindred with parathyroid carcinoma. AB - We report a family with primary hyperparathyroidism in four patients in two generations with apparent autosomal dominant transmission. A fifth member was probably affected. Two cases had definite parathyroid carcinoma (PC), and two had parathyroid adenoma with atypical features that could represent an early stage of cancer. In each of our patients, one parathyroid gland was abnormal. Five other parathyroid glands (in two patients) were normal in histology and size. There was no evidence of neoplasia in other tissues. Constitutional karyotypes were normal in all four patients. We identified three chromosomal abnormalities (a reciprocal translocation between chromosomes 3 and 4, trisomy 7, and a pericentric inversion in chromosome 9) in cultured PC tissue from one patient. These chromosomal changes are of unclear significance. Analyses on tumor DNA from one case of PC and one of atypical adenoma showed no evidence of ras gene mutations, PTH gene rearrangement, or allelic loss from chromosome 11q13 (locus of the gene for multiple endocrine neoplasia type 1). This family shows susceptibility to cancer without antecedent hyperplasia in all parathyroids. It could help identify a novel tumor susceptibility gene. PMID- 1639937 TI - Development of melatonin production in infants and the impact of prematurity. AB - The development of rhythmic 6-sulfatoxymelatonin excretion in urine was studied in healthy full-term and premature infants during the first 12 months of life. There was little evidence of rhythmic 6-sulfatoxymelatonin excretion before 9 to 12 weeks of age in full-term infants. Over this period, excretion increased five to six times compared to the excretion at 6 weeks (08 +/- 103 vs. 2973 +/- 438 pmol/24 h) with the major proportion of the hormone metabolite being excreted between 0200-1000 h. At 24 weeks of age, total 6-sulfatoxymelatonin excretion was 25% of adult levels. Premature infants (51 +/- 4 days premature) had a delay in the appearance of rhythmic 6-sulfatoxymelatonin of approximately 9 weeks. Even after correcting for gestational age or length of time at home, the premature infants were found to have a 2-3 week delay in the development of 6 sulfatoxymelatonin rhythmicity compared to full-term infants. These results provide evidence that neural centers responsible for rhythm generation and/or the pineal gland fail to accelerate their development after premature delivery. This may be due to the environment the infants are exposed to during their stay in hospital, particularly the pattern and intensity of lighting. PMID- 1639938 TI - Food contains the bioactive peptide, cyclo(His-Pro). AB - Cyclo(His-Pro) (CHP) is a cyclic dipeptide with numerous biological activities. As small di- and tripeptides may be absorbed intact when ingested orally, we were interested in examining several common foods for the presence of cyclo(His-Pro) like immunoreactivity (CHP-LI). In all foods tested, CHP-LI was found at levels 5 1500 times those previously found in human plasma. This CHP-LI was identical to authentic CHP by immunoidentity and chromatographic behavior. We conclude that 1) CHP-LI is readily detectable in several common food sources; 2) this CHP-LI is indistinguishable from authentic CHP; and 3) it is likely the CHP-LI in foods is absorbed in quantities sufficient to cause elevations of CHP-LI in plasma to biologically significant levels. PMID- 1639939 TI - Simultaneous assessment of insulin secretion and insulin sensitivity using a hyperglycemia clamp. AB - A hyperglycemic clamp is an established method to assess insulin secretion and is generally used only for this purpose. To determine whether it could also be used to assess insulin sensitivity, we compared insulin sensitivity indices (ISI) obtained during euglycemic and hyperglycemic clamp experiments in 22 nonobese volunteers (body mass index, 23.9 +/- 0.6 kg/m2) and in 20 obese individuals (body mass index, 30.8 +/- 1.3 kg/m2) matched for age and gender. The ISI values (micromoles per kg.min/pmol) of the obese group assessed during hyperglycemic (0.088 +/- 0.011) and euglycemic (0.050 +/- 0.005) clamp experiments were both significantly lower than the ISI of the nonobese group assessed in hyperglycemic and euglycemic clamp experiments (0.179 +/- 0.024 and 0.096 +/- 0.009, respectively; both P less than 0.01). Although the ISI values obtained with hyperglycemic clamps were consistently greater than those obtained with euglycemic clamp (0.137 +/- 0.016 vs. 0.075 +/- 0.007; P less than 0.001), they were highly correlated (r = 0.84; P less than 0.0001). Moreover, when these indices were converted to clearance rates, thereby correcting for the mass action effects of glucose on glucose disposal, the values obtained with the hyperglycemic clamp (0.0137 +/- 0.0016 mL/kg.min/pmol) were statistically identical to those obtained with the euglycemic clamp (0.0142 +/- 0.0013 mL/kg.min/pmol), as indicated by a regression equation having an intercept of 0 and a slope (1.03) not different from 1. We, therefore, conclude that the hyperglycemic clamp and the euglycemic clamp yield comparable estimates of insulin sensitivity and that, under appropriate conditions, the hyperglycemic clamp technique may be used to assess both insulin sensitivity and insulin secretion in the same individual in a single experiment. PMID- 1639940 TI - Determinants of bone density in young women. I. Relationships among pubertal development, total body bone mass, and total body bone density in premenarchal females. AB - Bone mass accretion during puberty appears to be critical in the development of peak bone mass, which, in turn, is believed to be a major determinant of osteoporosis risk. Although genetics may be the primary determinant of peak bone mass, modifiable secondary factors, such as nutrition and hormone exposure, may significantly affect bone mass accretion during the second decade of life. As part of a longitudinal study of major determinants of bone development during puberty, we obtained cross-sectional measurements from 112 premenarchal caucasian females (mean +/- SD age, 11.9 +/- 0.49 yr at study entry). Total body bone mineral density (TBBMD) and total body bone mineral content (TBBMC) were measured by dual energy x-ray absorptiometry and compared to anthropometric, pubertal development, urinary steroid and gonadotropin levels, and nutrient intake. An integrated estrogen exposure index was developed and used to evaluate the cumulative effect of circulating estrogen levels on both development. Compared to normative reference data for adults, our subjects possessed 90% of adult height, 68% of adult weight, 83% of adult TBBMD, and 53% of TBBMC. The strongest combined predictors of prepubertal TBBMD and TBBMC were body weight, followed by height and pubertal development. Urinary estradiol levels were positively correlated with dietary intake of iron and vitamin B6. PMID- 1639941 TI - Effective suppression of luteinizing hormone and testosterone by single doses of the new gonadotropin-releasing hormone antagonist cetrorelix (SB-75) in normal men. AB - In rats and nonhuman primates the new GnRH antagonist cetrorelix (SB-75; [Ac-D Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,D-Cit6,D-Ala10]GnR H) has been shown to suppress testosterone secretion effectively and persistently. A clinical phase I study was performed to assess the hormonal effects of this highly potent antagonist in normal men. After 2 control examinations 30 young male volunteers were randomly assigned to 6 treatment groups (n = 5/group), and single doses of 0 (placebo), 0.25, 0.5, 1.0, 2.0, and 5.0 mg cetrorelix were administered sc. Blood samples were obtained over the course of 7 days postinjection. After maximal cetrorelix serum levels were achieved 1 h postinjection, the GnRH antagonist serum levels decreased with a terminal t1/2 of 29.8 +/- 4.2 h (mean +/- SE). LH secretion was suppressed dose- and time-dependently; maximal suppression occurred 4-6 h postinjection. Suppression of FSH did not reach statistical significance. Doses of 1.0, 2.0, and 5.0 mg cetrorelix significantly suppressed testosterone secretion compared to that in the placebo group. After the administration of 1.0 mg cetrorelix, maximal suppression was seen 8 h after injection, with testosterone levels of 7.5 +/- 1.1 nmol/L compared to 15.8 +/- 2.2 nmol/L in the placebo group. Maximal testosterone suppression by 2.0 and 5.0 mg cetrorelix occurred 12 h after injection, with testosterone concentrations of 4.9 +/- 0.5 and 2.2 +/- 0.4 nmol/L, respectively, compared to 16.5 +/- 1.7 nmol/L in the placebo group. Twenty-four hours after the injection of 1.0 and 2.0 mg cetrorelix, testosterone values were no longer significantly different from those in the placebo group, whereas in the 5.0-mg dose group testosterone concentrations increased slightly and reached serum concentrations in the lower normal range after 48 h. The only side-effect observed after the administration of cetrorelix was a transient local erythema at the injection site that disappeared within 30 min. No local induration or pruritus, or any adverse systemic side-effect occurred in any volunteer. In conclusion, the new GnRH antagonist cetrorelix effectively decreases serum LH and testosterone concentrations in a dose- and time-dependent manner and, therefore, has potential for treatment of sex hormone-dependent diseases and male contraception. PMID- 1639942 TI - Age-dependent effect of resistance exercise on growth hormone secretion in people. AB - We measured serum GH responses to a standardized circuit of resistance exercise in 12 young subjects (6 men and 6 women; 27 +/- 1.6 yr old) and in 11 elders (6 men and 5 women; 72 +/- 0.8 yr old). Initial assessment of strength [1 repetition maximum (1RM)] was made of 12 muscle groups using Nautilus equipment. One week later, subjects carried out the exercise protocol, 3 sets of 8 repetitions for each of the 12 exercises, at 70% of predetermined 1RM values. Venous blood was drawn at baseline, after each exercise, and every 2 min during 10 min of recovery. In young subjects serum immunoreactive GH rose by completion of the second exercise, increased and remained elevated through the remainder of the exercise period, and decreased toward baseline by 10 min of recovery. In the elderly subjects, baseline GH values were similar to those in the young (1.76 +/- 0.41 vs. 2.61 +/- 0.73 micrograms/L) and did not increase above 6 micrograms/L at any time during or after exercise. Exercise increased GH in both groups, but peak values (14.9 +/- 3.5 micrograms/L in young; 2.44 +/- 0.6 micrograms/L in old) and integrated (198 +/- 47 in young; 37.8 +/- 0.8 in old) were significantly greater in the young subjects (P less than 0.05). GH responses showed no gender difference in either group. Brief increases in pulse rate were observed during individual exercises, but sustained elevations did not occur. To assess the effect of exercise intensity on GH response, we compared responses to exercise at 70% and 85% of 1RM in 7 young and 11 older people. In the young subjects, GH responses were nonsignificant at 60% and increased progressively at 70% and 85% of 1RM. No significant effect of exercise intensity was observed in the older subjects. We conclude that resistance exercise promptly elevates circulating GH concentrations in healthy young adults. This response is related to the intensity of the resistance stimulus, although a small contribution of aerobic stress cannot be excluded. The GH response to resistance activity is grossly diminished in healthy elderly men and women. PMID- 1639943 TI - Normal calcitonin stimulation of serum calcitriol in patients with X-linked hypophosphatemic rickets. AB - Patients with X-linked hypophosphatemic rickets (XLH) have normal or low calcitriol concentrations despite manifesting hypophosphatemia, a known stimulus of 25-hydroxyvitamin D-1 alpha-hydroxylase activity. In accord, administration of pharmacological doses of PTH results in a markedly blunted stimulation of calcitriol levels. In the murine homolog of the human disorder, the Hyp mouse, regulation of 25-hydroxyvitamin D-1 alpha-hydroxylase activity is defective in response to hypophosphatemia and PTH administration, but not in response to calcitonin administration. In the current study we administered calcitonin to controls and patients with XLH to test the hypothesis that calcitonin stimulatable 25-hydroxyvitamin D-1 alpha-hydroxylase activity is normal in patients with XLH. We found that calcitriol concentrations increased in both groups to a similar degree (78.5 +/- 20.9 pmol/L in patients and 49.9 +/- 19.7 pmol/L in controls) and with a similar time course. Our results indicate that the complex and incomplete defect in the regulation of 25-hydroxyvitamin D-1 alpha hydroxylase observed in Hyp mice also exists in humans. PMID- 1639944 TI - Effects of a physiological growth hormone pulse on substrate metabolism in insulin-dependent (type 1) diabetic subjects. AB - When present in inappropriate amounts GH induces substantial insulin resistance and it has furthermore been suggested that modest nocturnal surges of GH may precipitate the emergence of the dawn phenomenon. To characterize the metabolic effects of physiologically relevant, small-scale GH exposure, six type 1 diabetic subjects were studied for 5 h in the postabsorptive state after an iv pulse of either 210 micrograms GH or saline. Identical amounts of insulin were infused on both occasions to maintain a prevailing blood glucose concentration of 125 +/- 12 mg/100 ml. The GH bolus caused an increase in serum GH levels to a peak value of 22 +/- 2 micrograms/L after 10 min, a 70% increase in serum FFA (from 570 +/- 80 to 980 +/- 60 mumol/L) and a 400% increase in blood 3-hydroxybutyrate (3-OHB) (from 100 +/- 15 to 420 +/- 35 mumol/l) concentrations after 180 and 240 min respectively (P less than 0.05). Blood glycerol and forearm uptake of 3-OHB rose in parallel (P less than 0.01). Plasma glucose, isotopically measured glucose turnover and forearm glucose uptake was not affected by GH. Blood lactate concentrations increased (P less than 0.05) and nonoxidative glucose use and lipid oxidation tended to increase with GH. Energy expenditure remained unaffected. These results suggest that under everyday conditions GH acts as an important regulator of fuel fluxes in type 1 diabetic subjects, the main effect being a transient stimulation of lipolysis. Since no significant effect on glucose metabolism was recorded, we do not presently find evidence to support a primary role for small surges of GH in the pathogenesis of the dawn phenomenon. PMID- 1639945 TI - Body fat mass, body fat distribution, and pubertal development: a longitudinal study of physical and hormonal sexual maturation of girls. AB - The rate at which girls progress through the stages of puberty in relation to body fat mass and body fat distribution and its relation to their hormonal profiles was studied. Sixty-eight schoolgirls participated in a longitudinal study during 3 yr. The girls were divided into subgroups with increasing skinfold thicknesses and waist-hip ratio. They were also grouped depending on Tanner's breast development classification (M2 and M3). The age at M2 was only marginally correlated with the menarcheal age, but the age at M2 and the time interval from that age to menarche was negatively correlated. Age at the onset of puberty was not related to body fat mass or distribution. The rate of pubertal development after pubertal stage M3 was negatively related to the body fat mass. Age at M2 was only correlated with estrone (E1), while the rate of pubertal development was associated with higher FSH, E1, estradiol (E2), the fraction of E2 that was not bound to sex-hormone-binding globulin (non-sex-hormone-binding globulin bound E2) and androstenedione plasma levels at the onset of puberty. Body fat distribution, rather than body fat mass was related to the total and the non-sex-hormone binding globulin bound plasma levels of E2 and testosterone at the onset of puberty. Changes in body fat distribution in early female puberty were chiefly related to the waist circumferences. We found no evidence that body fat mass or body fat distribution triggers the onset of puberty. Body fat distribution was related to early pubertal endocrine activity. Body fat mass was negatively related to the rate of pubertal development toward menarche, but no clear indications for an endocrine-related process is found. We conclude that onset of puberty and menarche are not parallel pubertal events, and that early pubertal plasma E1, E2 and androstenedione levels are predictors for the rate of pubertal development toward menarche. We propose that the control of the onset of puberty and maturation of the hypothalamic-pituitary gonadal axis, with regard to negative feedback control, are at least partially independent. This induces on the average a "catch up" pubertal maturation in girls with a late onset of puberty. PMID- 1639946 TI - Melatonin: a major regulator of the circadian rhythm of core temperature in humans. AB - The circadian rhythm of core body temperature (BTc), with maxima during the day and minima at night, is normally coupled with the sleep-wake cycle. Pineal melatonin secretion occurs contemporaneously during the nighttime hours and is mediated by the activation of beta-adrenergic receptors during darkness. The hypothesis that nocturnal melatonin secretion may be involved in the regulation of the human circadian BTc rhythm was examined. The temporal relationship between melatonin and the circadian BTc rhythm was characterized in 12 young women, normally entrained to the light-dark cycle. Melatonin levels were manipulated through the administration of exogenous melatonin (2.5 mg, orally) during the daytime (n = 6) or suppression of endogenous nocturnal melatonin secretion by the beta-adrenergic antagonist atenolol (100 mg; n = 6) in double blind placebo controlled experiments conducted during 2 consecutive days. Serum melatonin levels and BTc were monitored at 20- and 10-min intervals, respectively. In a nightshift worker the temporal relationship between the circadian rhythm of melatonin and BTc was investigated before and after entrainment to a reversed wake-sleep cycle. Our data show that in normally entrained subjects, the time course and amplitude of nocturnal melatonin secretion were temporally coupled with the decline of BTc (r = 0.97; P less than 0.00001). The same occurred in the nightshift worker, both during the dissociation and after entrainment to the reversed sleep-wake cycle. Compared with placebo, administration of melatonin significantly reduced daytime BTc (P less than 0.01), and the suppression of melatonin (by atenolol) attenuated the nocturnal decline of BTc (P less than 0.01). Cosinor analysis showed that the amplitude of the circadian BTc rhythm was reduced by about 40% in response to both daytime melatonin administration (P less than 0.05) and nocturnal melatonin suppression (P less than 0.02). In conclusion, circadian rhythms of melatonin and BTc are inversely coupled. The demonstrated hypothermic properties of melatonin are accountable for the generation of at least 40% of the amplitude of the circadian BTc rhythm. Manipulation of melatonin levels might be clinically useful to resynchronize the BTc rhythm under conditions of BTc rhythm desynchronization. PMID- 1639947 TI - Role of basal triglyceride and high density lipoprotein in determination of postprandial lipid and lipoprotein responses. AB - The present study reports on the interaction between basal triglyceride and high density lipoprotein (HDL) cholesterol in determining the magnitude of postprandial triglyceridemia. The vitamin A fat-loading test was used to label intestinally derived triglyceride-rich particles after a high fat meal in 18 subjects with low HDL cholesterol and 6 control subjects who had normal fasting triglyceride and HDL cholesterol levels. The patients with low HDL cholesterol were divided into 2 groups on the basis of their basal triglyceride concentrations; 11 had normal triglyceride levels, and 7 had elevated serum triglycerides (HTG). In the HTG-low HDL group, the incremental area under the triglyceride curve was significantly greater (P less than 0.0003) than that in the other 2 groups, between whom no significant differences in triglyceride response were observed. Retinyl palmitate levels measured in whole plasma, an Sf greater than 1000 chylomicron fraction, and an Sf less than 1000 nonchylomicron fraction were also significantly greater in low HDL subjects with HTG, while the concentrations in low HDL subjects with normal triglyceride levels and control subjects were similar. Although basal HDL cholesterol levels in all study subjects were negatively correlated with the area under the incremental triglyceride curve (r = -0.42; P less than 0.05), this correlation was weak, in contrast to the correlation between fasting triglyceride levels and incremental triglyceride area (r = 0.56; P less than 0.005). Furthermore, basal HDL cholesterol levels did not correlate with the area under the chylomicron or nonchylomicron curves, whereas basal triglyceride levels were significantly correlated (P = 0.0001) with both of these variables. The HDL particles of both low HDL groups had a significantly higher proportion of triglyceride compared to the HDL particles in the control subjects. In conclusion, 1) fasting triglyceride levels are a more powerful indicator of the postprandial lipid response than basal HDL cholesterol in subjects with low HDL cholesterol levels; 2) patients with low HDL cholesterol levels do not preferentially accumulate chylomicron remnants after a meal unless they have coexisting hypertriglyceridemia; and 3) abnormalities in the levels of triglyceride-rich particles post-prandially are unlikely to be responsible for the increased incidence of atherosclerosis in low HDL patients who are normotriglyceridemic. PMID- 1639949 TI - Onset and characteristics of the midcycle surge in bioactive and immunoactive luteinizing hormone secretion in normal women: influence of physiological variations in periovulatory ovarian steroid hormone secretion. AB - Limited studies in nonhuman primates suggest that the midcycle LH surge is characterized by distinctly different patterns of bioactive (LH-BIO) and immunoactive (LH-RIA) LH secretion. To further examine the patterns of midcycle LH-BIO and LH-RIA secretion and explore the influence of physiological variations in steroid hormone feedback on LH surge dimensions we studied seven normal ovulatory women over the periovulatory interval. In each, blood samples were obtained every 3 h and transvaginal ultrasonography was performed every 12 h over a 5-7 day interval at midcycle. Serum levels of LH-RIA, FSH, estradiol (E2), progesterone (P4), and 17-hydroxyprogesterone were determined by RIA; LH-BIO was estimated using a mouse leydig cell bioassay. Hormone data were standardized to the time of surge onset in LH-RIA (time zero), defined as a 100% increase above a 6-point running mean baseline value; surge cessation was defined as a decline to below baseline concentration. Mean LH-RIA surge duration was 54.0 +/- 4.0 h. LH BIO surge onset was simultaneous with that of LH-RIA and coincident with the peak in E2 levels (mean data). Mean P4 and 17-hydroxyprogesterone rose in a parallel, phasic manner, an abrupt increase in slope occurred between -6 h and +30 h but an acute rise in P4 was not consistently observed among individuals. The surge onset to follicle rupture interval (mean 37.6 +/- 4.2 h) positively correlated with peak LH-RIA (r = 0.76, P less than 0.05), surge amplitude (r = 0.74, P less than 0.05) and surge onset to peak interval (r = 0.87, P less than 0.02), but not surge duration. There were no significant relationships between E2 or P4 (mean, peak, integrated, slope) and surge amplitude or duration (LH-RIA, FSH), peak value, or surge onset to peak interval (LH-RIA, LH-BIO, FSH). These data suggest that in women, 1) onset of the midcycle surge in LH-RIA and LH-BIO is simultaneous, and 2) surge characteristics are not influenced by physiological variations in steroid hormone secretion that occur beyond the thresholds required for surge initiation. PMID- 1639948 TI - Induction of azoospermia in normal men with combined Nal-Glu gonadotropin releasing hormone antagonist and testosterone enanthate. AB - The effects of a combined GnRH antagonist and testosterone (T) replacement regimen on gonadotropins and spermatogenesis were examined to assess its potential as a male contraceptive regimen. The potent Nal-Glu GnRH antagonist ([Ac-D2-Nal1,D4-Cl-Phe2,D3-Pal3,Arg5, D4-p-methoxybenzoyl-2-amino butyric acid6,D Ala10]GnRH) was administered daily (7.5 mg, sc) to eight normal men for 16 weeks. T enanthate was given im starting at week 2 and every 2 weeks thereafter through week 14 of the treatment phase. Serum LH, FSH, T, and estradiol concentrations were measured frequently during the 5-week control period, the 16-week treatment phase, and the 14-week recovery phase. Semen analyses were performed every week during the control phase and every 2 weeks during the treatment and recovery phases. Seven of eight subjects became azoospermic by 6-10 weeks of treatment; the eighth subject, who failed to achieve azoospermia, suppressed his sperm count to 7 million/mL by week 14 (from a mean baseline of 42 million/mL) before treatment was prematurely terminated because of localized swelling at each of his injection sites. Sperm counts returned to baseline 10-14 weeks after the end of Nal-Glu administration. Seven of the eight subjects showed suppression of LH to the limit of assay detection (less than 0.2 U/L), whereas the eighth subject showed incomplete suppression. Serum bioactive and immunoreactive LH concentrations showed concordant responses. Mean serum FSH concentrations were also markedly suppressed. Serum T and estradiol concentrations declined dramatically during the first 2 weeks of Nal-Glu GnRH treatment, but returned to the normal physiological range after T enanthate replacement was initiated. Libido and sexual potency were maintained. No systemic side-effects, other than erythema and induration at injection sites, were observed. These data demonstrate that combined GnRH antagonist plus T treatment can predictably and reversibly induce azoospermia in most men and has potential as a male contraceptive regimen. PMID- 1639950 TI - Influence of vitamin D on parathyroid function in the elderly. AB - The effect of age and vitamin D status on parathyroid function was studied in 129 healthy subjects between 20 and 89 yr old, with normal serum creatinine (less than 0.11 mmol/L), and living in Cordoba, Spain. Serum calcium and phosphorus as well as 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D [1,25-(OH)2D] decreased, whereas serum alkaline phosphatase increased, with age. Serum PTH also increased significantly with age when measured with either a carboxyl-terminal (cPTH) or an intact [PTH(1-84)] assay. The increase in cPTH, however, exceeded largely the increase in PTH(1-84) (+120% and +30% in subjects above 80 yr vs. young adults, respectively). Serum PTH(1-84) was negatively correlated with serum (ionized) calcium, 25OHD, and insulin-like growth factor I (IGF-I) but not with serum 1,25-(OH)2D. Serum 1,25-(OH)2D decreased with age and was highly correlated with serum 25OHD, cPTH, and IGF-I. In multiple regression analysis 50-60% of the variation of total and free 1,25-(OH)2D could be explained by serum 25OHD, PTH(1 84), and especially IGF-I, suggesting a possible role of decreasing GH and IGF-I concentrations in the mineral homeostasis of the elderly. Calcium infusion (1.5 mg/kg body weight over 10 min) decreased serum PTH(1-84) to below normal concentrations in young adults (nadir 14% of basal concentration), whereas the nadir in elderly subjects with secondary hyperparathyroidism was only 32% of basal concentration. The relative decrease was, however, identical in both age groups when simultaneous changes in ionized calcium were taken into account. Basal serum PTH(1-84) in selected elderly subjects (50 +/- 10 ng/L or 5 +/- 1 pmol/L, n = 10) decreased significantly (2.7 +/- 0.9 pmol/L, P less than 0.01) after 3 iv injections of 1,25-(OH)2D during 1 week without changes in serum (ionized) calcium. The PTH suppressibility after calcium infusion did not further improve. IN CONCLUSION: elderly patients with normal serum creatinine had a small (+30%) but significant increase in intact serum PTH concentration but the mean concentration still remained within the normal range. The PTH secretion remained normally suppressible by acute calcium infusion. Treatment with 1,25-(OH)2D decreased basal calcium-PTH setpoint without further additional effects during calcium infusion. PMID- 1639951 TI - Administration of human luteinizing hormone (hLH) to macaques after follicular development: further titration of LH surge requirements for ovulatory changes in primate follicles. AB - After stimulation of multiple follicular development, endogenous LH surges elicited by GnRH or GnRH agonist were of insufficient duration (4-14 h) to evoke oocyte maturation and luteinization in this species. In this study, periovulatory LH surge requirements were further titrated using hLH as the ovulatory stimulus. Beginning at menses, rhesus monkeys were treated with human gonadotropins for 9 days to stimulate follicular growth. To induce ovulatory maturation on day 10, animals received: 1) hCG (1000 IU, im; n = 8); 2) highly-purified, urinary hLH (2542 IU, im; n = 4); or 3) hLH (2542 IU, im) followed by three injections of hLH (200 IU, im) at 8-h intervals (0800, 1600, 2400 h) daily during the luteal phase until menses (n = 3). Oocytes and luteinizing granulosa cells were obtained via follicle aspiration 27 h after the initial hLH or hCG injection. Estradiol and progesterone levels were measured in daily serum samples by RIA. Bioactive LH levels were determined at selected intervals within 36 h of the hLH ovulatory stimulus. Nuclear maturity of oocytes was evaluated as an indicator for reinitiation of meiosis. Luteinizing granulosa cells were processed for indirect immunocytochemistry using a monoclonal antibody to human progesterone receptor. In vitro progesterone production by luteinizing granulosa cells over 24 h was also assessed in the absence and presence of hCG. In all groups, serum estradiol rose to similar peak levels on day 10. After hLH, bioactive LH levels peaked (1262 +/- 79 ng/mL; mean +/- SEM) by 2-6 h, declined thereafter but remained above surge levels (100 ng/mL) for 18-24 h. Within 24 h of hLH injection, serum progesterone increased to 13 +/- 3 nmol/L, but returned to baseline in 1-6 days. In contrast, higher levels of progesterone were observed after hCG (114 +/- 51 nmol/L) and during luteal phase treatment with hLH (137 +/- 25 nmol/L) and the luteal phase was longer (11.5 +/- 0.4 and 14.3 +/- 0.7 days, respectively). Of the total cohort of oocytes aspirated, the proportion of oocytes resuming meiotic maturation (metaphase I plus metaphase II) was similar after hCG (76%) and hLH (74%). However, the proportion of oocytes maturing to metaphase II tended to be less (P = 0.08) after hLH (13%) than hCG (22%). Fertilization rates were similar between the two groups. Progesterone receptor was detected in nuclei of luteinizing granulosa cells from all animals receiving hCG, but only in some given hLH.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1639953 TI - Hypothalamic-pituitary-thyroidal function in eumenorrheic and amenorrheic athletes. AB - The impact of chronic high volume athletic training on thyroid hormone economy has not been defined. We investigated the status of the hypothalamic-pituitary thyroid axis (H-P-T) in women athletes with regular menstrual cycles (CA) and with amenorrhea (AA). Their data were compared with each other and with those derived from cyclic sedentary women (CS) matched for a variety of confounding factors including the intensity of exercise, caloric intake, and body weight. Alterations of the H-P-T axis were observed in women athletes compared to CS. While serum levels of T4, T3, free T4, free T3 and rT3 were substantially reduced (P less than 0.01) in AA, only serum T4 levels were significantly decreased in CA. Further, remarkable differences were found between CA and AA in that serum levels of free T4 (P less than 0.01), free T3 (P less than 0.01), and rT3 (P less than 0.05) were significantly lower in AA than in CA. Thyroid binding globulin and sex-hormone binding globulin concentrations were within their normal ranges for all groups of subjects. Both 24-h mean TSH levels and the circadian rhythm of TSH secretion were also comparable. However, the TSH response to TRH stimulation was blunted (P less than 0.01) in AA when compared to CA, but not to CS. Whereas the underlying mechanism(s) to account for the "global" reduction of circulating thyroid hormone in the face of normal TSH levels in AA is presently unknown, these observations provide information of clinical significance: 1) chronic high volume athletic training in women athletes with menstrual cyclicity is accompanied by an isolated T4 reduction; 2) an impaired H-P-T axis occurs selectively in athletic women in whom chronic high volume athletic training is associated with compromised hypothalamic-pituitary-ovarian function and amenorrhea. PMID- 1639952 TI - Polycystic ovary syndrome: lack of hypertension despite profound insulin resistance. AB - It has been hypothesized that insulin resistance and hyperinsulinemia contribute to the development of arterial hypertension. To further investigate this relationship, we compared arterial blood pressure in controls and women with polycystic ovary syndrome (PCO), an insulin-resistant state. Fourteen PCO women and 18 normal control women of similar age, body mass index, and race were studied. Plasma glucose and insulin levels were determined in an oral glucose tolerance test. The insulin sensitivity (SI) index was determined by the minimal model method. Systolic and diastolic blood pressure were measured by 24-h ambulatory monitoring. Left ventricular mass was assessed by echocardiography. The two groups had comparable fasting glucose levels, but the 2-h postload glucose was higher in PCO (8.0 +/- 0.5 vs. 5.6 +/- 0.3 mmol/L; P less than 0.001). Compared to controls, PCO women were significantly more insulin resistant by fasting insulin, 2-h insulin concentrations, and SI (28.3 +/- 6.7 vs. 68.3 +/- 10.0 min-1/nmol.mL; P less than 0.01). Average ambulatory systolic (121 +/- 2 vs. 118 +/- 2 mm Hg) and diastolic (76 +/- 2 vs. 73 +/- 2 mm Hg) blood pressures were similar for PCO and control women. No difference was found in left ventricular mass. Therefore, despite profound insulin resistance and hyperinsulinemia, women with PCO do not have increased arterial pressure or left ventricular mass. PMID- 1639954 TI - Progestin antagonism of estrogen stimulated 1,25-dihydroxyvitamin D levels. AB - Progestins are frequently used in combination with estrogen to prevent or treat postmenopausal osteoporosis. Progestins protect against the undesirable hyperplastic effects of estrogen on the endometrium. The possibility that progestins might antagonize the beneficial effects of estrogen on calcium homeostasis has received little attention. In this study we determined whether the addition of progestin to estrogen would alter the ability of estrogen to raise serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels. Women within 5 yr of menopause were treated with three cycles of oral unopposed estrogen [1 or 2 mg/day (3.67 or 7.34 mumol/day) 17 beta-estradiol (E2) for 25/30 days of each cycle] followed by three cycles of E2 plus progestin [10 mg/day (29 mumol/day) medroxyprogesterone on days 12-25]. E2 increased both total and free 1,25-(OH)2D concentrations in a dose-dependent fashion. These levels increased progressively over the three cycles of unopposed estrogen treatment. In contrast the vitamin D binding protein concentration reached maximal levels after one cycle of E2. With the addition of progestin, the levels of total and free 1,25-(OH)2D returned toward baseline although vitamin D binding protein levels remained elevated. PTH levels rose with both doses of E2 as serum calcium levels fell. Progestin did not significantly alter the effects of E2 on PTH or calcium. Our results raise the possibility that progestin may antagonize part of the salubrious effects of estrogen on calcium homeostasis. PMID- 1639955 TI - Epidemiology of menarche and menstrual disturbances in an unselected group of women with insulin-dependent diabetes mellitus compared to controls. AB - To describe the age at menarche and the prevalence of menstrual disturbances in an unselected group of women with insulin-dependent diabetes mellitus compared to controls, we identified all women having debut of diabetes mellitus before the age of 30 yr and living in the County of Funen, Denmark on July 1, 1987 and being between 18 and 49 yr old. The women received a structured questionnaire inquiring information concerning menstrual conditions. An age comparable group of nondiabetic women was used as controls; 245 (94%) diabetic women and 253 (88%) controls answered the questionnaire. Among women with debut of diabetes before the age of 10 yr, the age at menarche was delayed 1 yr when comparing to controls (P less than 0.0001). During the past 6 months before answering the questionnaire, 8.2% of the diabetic women and 2.8% of the controls had experienced episodes of secondary amenorrhea (P less than 0.01). Corresponding figures for oligomenorrhea were 10.6% and 4.8% (P less than 0.02), for polymenorrhea 7.3% and 5.2% (NS), and for all types of menstrual disturbances 21.6% and 10.8%, respectively (P less than 0.005). Episodes of secondary amenorrhea occurring more than 6 months before answering the questionnaire had been experienced by 10.7% of the diabetic population vs. 4.8% of the controls (P less than 0.05); corresponding figures for primary amenorrhea were 4.9% and 1.2%, respectively (P less than 0.05). We conclude that the age at menarche among women having developed insulin-dependent diabetes mellitus before the age of 10 yr was delayed by 1 yr when compared to controls. The overall prevalence of menstrual disturbances is increased in diabetic women compared to nondiabetic controls. PMID- 1639956 TI - Corticoid-induced growth hormone (GH) secretion in GH-deficient and normal children. AB - Acute administration of corticoids is a potent stimulus of GH secretion in man. To ascertain their mechanism and point of action as well as the suitability of this novel test in the diagnosis of GH-deficient states, normal controls and GH deficient children were studied. They were selected based on auxological criteria and the GH response to provocative stimuli. The GH-deficient children presented a blunted GH (mean +/- SEM; microgram/L) discharge after insulin-induced hypoglycemia (2.9 +/- 0.4), propranolol-exercise (7.4 +/- 1.5), and clonidine (6.5 +/- 0.8) compared with values in the normal children (7.2 +/- 2.2, 15.8 +/- 2.4, and 15.6 +/- 1.8, respectively). As expected, GH-releasing hormone (GHRH) induced GH discharge in GH-deficient children (33.2 +/- 4.9) was similar to that in the control children (35.1 +/- 6.0). Administration of 2 mg/m2 body surface dexamethasone, iv, to normal children induced, 3 h later, a mean GH peak of 14.1 +/- 1.2 micrograms/L. This was significantly higher that the corticoid-induced GH peak in GH-deficient children (6.7 +/- 1.1 micrograms/L). The corticoid-induced areas under the secretory curve were 1130 +/- 55 and 616 +/- 54 for the control and GH-deficient children, respectively. GH release in children after dexamethasone administration followed the pattern previously described for adults, i.e. there were no modifications of basal GH levels in the first 2 h, the GH peak appeared around the third hour, and the GH levels remained increased until the fourth hour after dexamethasone administration. Individually considered, practically all control children, but only 2 of 12 GH-deficient children, presented a dexamethasone-induced GH peak over the 10 micrograms/L level. In both normal and GH-deficient patients, corticoids appeared just as potent a stimulus as propranolol-exercise and clonidine, and more potent than hypoglycemia. This new stimulus showed a pattern similar to that of the hypothalamic stimuli, but clearly different with respect to the pituitary one (GHRH), suggesting that corticoids activate GH secretion by acting at hypothalamic level. In conclusion, acute administration of corticoids could be a suitable test in the diagnostic armamentaria of GH-deficient states. PMID- 1639957 TI - Aldosterone-secreting adrenal adenoma as part of multiple endocrine neoplasia type 1 (MEN1): loss of heterozygosity for polymorphic chromosome 11 deoxyribonucleic acid markers, including the MEN1 locus. AB - A 63-year-old female presented with the extremely rare occurrence of an aldosterone-secreting adrenocortical adenoma as part of the syndrome of multiple endocrine neoplasia type 1 (MEN1). Only two other MEN1 patients were reported in the literature with hyperaldosteronism. The patient's MEN1 syndrome consisted of the association of primary hyperparathyroidism due to parathyroid adenoma, a prolactinoma, and a toxic multinodular goiter. Elevated basal and meal-stimulated serum PP levels without demonstrable pancreatic tumor were also found. Genetic analysis of the aldosterone-secreting adenoma with DNA markers localized on chromosome 11 showed loss of heterozygosity in tumor DNA. Since the MEN1 syndrome is caused by loss of the tumor suppressor gene on chromosome 11 in the 11q13 region, it is probable that the same mechanism is associated with the formation of the adrenocortical adenoma. PMID- 1639958 TI - Localization and regulation of the activin-A dimer in human placental cells. AB - Subunits of activin and inhibin and their mRNAs are present in human placental and decidual cells. However, evidence for the presence of intact activin dimers in the human placenta and their regulation has been lacking. Using a monoclonal antibody raised against the human activin-A dimer, we examined the cellular localization of immunoreactive activin-A dimer in human placentas of different gestational ages (8-41 weeks). In addition, we determined the effects of culture and various potential regulators on the cellular accumulation of immunoreactive activin-A dimer in trophoblast cells from human first trimester placentas. Activin-A dimer was found in both cyto- and syncytiotrophoblast cells of all gestational ages studied. Immunoreactive activin-A also was detected in placental Hofbauer cells in first and second trimester placentas as well as in cells of the placental membranes. Exposure of these cells to cAMP, GnRH, activin, inhibin, transforming growth factor-beta, dexamethasone, and interleukin-1 did not significantly change the intensity of immunostaining for activin-A dimer. These results together with previous data suggest that placental cells are a source of activin-A and that activin-A may be a paracrine and/or endocrine regulator of feto-maternal interactions during pregnancy. PMID- 1639959 TI - Steroid hormones regulate the release of immunoreactive beta-endorphin from the Ishikawa human endometrial cell line. AB - Immunoreactive beta-endorphin (IR-beta END) is present in human endometrium. Several indirect lines of evidence suggest that endometrial beta END is under steroid hormone control, i.e. IR-beta END is detectable in the secretory, but not the proliferative, endometrium, and progesterone administration increases the concentration of IR-beta END in uterine secretions of ovariectomized gilts. To study the effect of steroid hormones on endometrial beta END, we first questioned whether Ishikawa human endometrial adenocarcinoma cells (which respond to steroid hormones) express the proopiomelanocortin (POMC) gene. Indeed, on Northern blot analysis, a RNA similar or identical in size to pituitary POMC mRNA was present in Ishikawa cell RNA extracts. IR-beta END was also present in Ishikawa cell extracts and culture medium, which coeluted with synthetic human beta END in a Sephadex G-50 column. Ishikawa cells released most of their IR-beta END into the culture medium. Estradiol decreased the release of IR-beta END from Ishikawa cells, an effect that was dependent upon dose and time. The maximal effect was observed after a 4-day exposure to 10 nM estradiol (44 +/- 6% of the control value; n = 6; P less than 0.001). This effect was almost completely counteracted by a 100-fold excess of the antiestrogen 4-hydroxytamoxifen. Progesterone and dihydrotestosterone did not have a statistically significant effect on IR-beta END release. Dexamethasone had effects similar to those of estradiol, i.e. decreased the release of IR-beta END in a time- and dose-dependent manner. The maximal effect was detected after a 4-day exposure to 10 nM dexamethasone (53 +/- 6% of the control value; n = 6; P less than 0.001). Interestingly, the antiprogestin-antiglucocorticoid RU486 exhibited agonistic properties, i.e. diminished the release of IR-beta END in a time- and dose-dependent fashion, possibly via the glucocorticoid receptor. Its maximal effect was reached after a 4-day exposure to 10 nM RU486 (55 +/- 6% of the control value; n = 6; P less than 0.001). In conclusion, our data demonstrate that the release of IR-beta END from Ishikawa cells in culture is inhibited by estradiol and dexamethasone, suggesting that endometrial beta END is under estrogen and glucocorticoid regulation, as is the case with hypothalamic and pituitary POMC-derived peptides. This is the first time that the in vitro release of a peripheral-extracranial POMC-derived peptide has been found to be under the direct control of estrogens and glucocorticoids. PMID- 1639961 TI - Steroid hormones during puberty: racial (black-white) differences in androstenedione and estradiol--the Bogalusa Heart Study. AB - A large biracial cross-section of 1038 healthy children aged 6-18 yr with 519 blacks, 519 whites, 678 males, and 360 females was evaluated for Tanner stage and serum levels of androstenedione, dehydroepiandrosterone-sulfate, estradiol, progesterone, and testosterone. The anthropometric values of the blacks and whites were very similar at each Tanner stage with only minor differences in age, height, and weight related to an earlier onset of puberty in blacks. The hormones dehydroepiandrosterone-sulfate, progesterone, and testosterone did not exhibit any racial differences. Estradiol showed a significantly higher level among black males compared to white males (P less than or equal to 0.05) whereas androstenedione was significantly higher in both white males (P = 0.0001) and females (P less than or equal to 0.01) compared with blacks. Many hormones are known to effect insulin resistance and others have reported a correlation between insulin levels and androstenedione. Blacks suffer disproportionately from diabetes. Since puberty is a time of dramatic changes in insulin resistance, racial (black-white) differences in steroid hormone changes were explored. This study shows that a racial difference in androstenedione levels exist during puberty, at a time when racial differences in insulin resistance are becoming manifest. PMID- 1639960 TI - A direct immunoradiometric assay for human plasma prorenin: concentrations in cycling women and in women taking oral contraceptives. AB - Two synthetic penta deca peptides corresponding to the N-terminal portion (amino acid sequence 1-15) and the C-terminal portion (sequence 32-46) of the pro moiety of the human prorenin (PR) molecule were coupled to BSA and used as antigens to generate antibodies against PR. In a RIA system using the 125I-labeled peptide as tracer, it could be shown that antibodies against peptide 32-46 bound the peptide and the native PR in the follicular fluid (FF) to a similar degree, whereas antibodies generated against peptide 1-15 did not specifically recognize native PR. The specificity of the PR-(32-46) antibodies for PR was demonstrated by comparative measurements of PR by RIA and by an indirect procedure (involving trypsin treatment of PR) in different individual FF samples, plasma samples, and fractions of FF obtained by gel filtration or immunoaffinity chromatography. Normal plasma PR levels could not be measured by RIA, since they were below the detection limit of the assay (0.5 micrograms PR/L approximately 10 pmol/L). For measurement of the low PR levels in plasma, a sensitive direct immunoradiometric assay with a detection limit of 0.1 fmol PR/tube was developed. It was based on the combined action of a commercially available solid phase renin antibody and the affinity-purified and 125I-labeled PR-(32-46) antibody. The measurement of 35 individual plasma samples with different PR concentrations showed an excellent correlation (r = 0.99) between the new direct and the conventional indirect assays. The direct assay of PR concentrations in plasma of healthy women during the length of a menstrual cycle resulted in a biphasic pattern of PR concentrations, with peak levels (approximately 3-fold increase) at the time of the LH surge. The intake of monophasic and triphasic contraceptives caused a suppression of normal PR concentrations (96.9 +/- 34 ng/L; early follicular phase; n = 12) by 39% and 25%, respectively, which was also observed in the pill free phase of the artificial cycle. PMID- 1639962 TI - Flow cytometric analysis of deoxyribonucleic acid in human granulosa cells as a function of chronological age and ovulation induction regimen. AB - We examined whether the proliferative index of granulosa cells as determined by flow cytometry varied with a women's age or ovulation induction regimen that included leuprolide acetate (LA). This prospective cohort study included three groups of patients undergoing assisted reproductive technologies. Group I consisted of 9 women age less than or equal to 30 yr, who received LA plus human menopausal gonadotropin (hMG). Group II included 9 women age more than or equal to 40 yr, who received LA plus hMG. Group III consisted of 6 women age less than or equal to 30 yr who received hMG alone. A total of 79 preovulatory follicles containing greater than 10(4) granulosa cells were obtained from these 24 women and examined by flow cytometry. Group I was compared to group II to match for ovulation induction regimen and to examine proliferative index as a function of age. Group I was compared to group III to match for age and to examine proliferative index as a function of ovulation induction regimen. Outcome measures included proliferative index of granulosa cells as a function of age, ovulation induction regimen, ampules of hMG, estradiol on day of hCG, and serum FSH. Group I demonstrated a greater proliferative index than group II: 23.4% +/- 1.4 vs. 18.4% +/- 0.96 (P less than 0.01). Group I had a greater proliferative index than group III: 23.4% +/- 1.4 vs. 11.9 +/- 0.61 (P less than 0.001). Although both age and the presence of LA appeared to affect the PI, multiple linear regression demonstrated that only the addition of LA and not age, per se, had an independent effect upon granulosa cells undergoing proliferation (P less than 0.0005). We conclude that LA followed by hMG leads to an increase in the percentage of granulosa cells undergoing proliferation when compared to ovulation induction regimens that include hMG alone. Chronological age does not appear to have a significant independent influence upon the proliferative index. PMID- 1639963 TI - The regulation of endothelin production in human umbilical vein endothelial cells: unique inhibitory action of calcium ionophores. AB - Endothelins (ETs) are a recently discovered family of small proteins that have potent long-lasting vasoconstrictive activities. Increased circulating concentrations of ETs have been found in hypertensive and renal disorders, including pregnancy-induced hypertension (PIH). PIH has been postulated to be the end result of endothelial cell damage and aberrant calcium metabolism. We evaluated the effects of calcium ionophores, calcium channel blockers, and two forms of cellular damage on ET production by human umbilical vein endothelial cells (HUVEC). Cells were grown to confluence and then incubated for 16 h with these treatments: physical trauma ("scratching"), oxidant damage (hydrogen peroxide, 1-20 mM), ionomycin (0.25-2.0 microM), A-23187 (10(-9)-10(-5) M), verapamil (0.22-22.0 microM), and nifedipine (2-200 micrograms/mL). ET production was determined using a commercial RIA that detects ET-1 and ET-2. Physical trauma enhanced ET production, whereas oxidant damage had the opposite effect. Both ionomycin and A-23187 caused concentration-dependent inhibition of ET production. Neither verapamil nor nifedipine consistently altered ET production. We conclude that specific forms of cellular damage can stimulate HUVEC ET production, although oxidant damage may be slightly inhibitory. Thus, enhanced ET levels in PIH may represent endothelial cell activation, rather than damage. HUVEC ET production is regulated in an inverse manner by intracellular calcium concentrations, suggesting a negative feedback from mediators of ET action on cells. PMID- 1639964 TI - Melatonin augments the sensitivity of MCF-7 human breast cancer cells to tamoxifen in vitro. AB - Cultured MCF-7 human breast cancer cells were pre-exposed to either melatonin (232 ng/mL) or vehicle for 24 hrs prior to being washed and then re-exposed to either ethanol-vehicle or varying concentrations of tamoxifen (37.1 ng/mL, 3.71 micrograms/mL, 371 micrograms/mL) or melatonin (2.32 pg/mL, 232 ng/mL, 23.2 ng/mL) for 5 additional days. Only 371 ng/mL tamoxifen caused a 38% growth inhibition of cells pre-exposed to vehicle whereas all concentrations of tamoxifen inhibited the growth of melatonin pre-exposed cells by 28% to 61% in a dose-dependent manner. Melatonin pre-exposure, potentiated the inhibitory effect of only 232 ng/mL melatonin. Comparison of IC50 values indicate that tamoxifen is approximately a 100 times more potent inhibitor of breast cancer cell growth following the pretreatment of cells with a physiological concentration of melatonin. These results indicate that melatonin has the capability to augment the inhibitory actions of tamoxifen, and to a lesser extent itself, on human breast cancer cell growth. PMID- 1639965 TI - Citation for the Ernst Oppenheimer Award of the Endocrine Society to James Larry Jameson. PMID- 1639966 TI - Citation for the Richard E. Weitzman Memorial Award to Fred E. Cohen. PMID- 1639967 TI - Citation for the Fred Conrad Koch Award of the Endocrine Society to Melvin M. Grumbach and Selna L. Kaplan. PMID- 1639968 TI - Citation for the Edwin B. Astwood Lectureship of the Endocrine Society to Michael O. Thorner. PMID- 1639969 TI - Citation for the Sidney H. Ingbar Distinguished Service Award to Nettie Karpin. PMID- 1639970 TI - Citation for the Robert H. Williams Distinguished Service Award to Claude J. Migeon. PMID- 1639971 TI - Citation for the Rhone-Poulene Rorer Pharmaceutical Clinical Investigator Award of the Endocrine Society to Samuel S. C. Yen. PMID- 1639972 TI - Preimplantation genetic diagnosis--counting chickens before they hatch? PMID- 1639973 TI - In-vitro progesterone production of human granulosa--luteal cells: the impact of different stimulation protocols, poor ovarian response and polycystic ovarian syndrome. AB - Granulosa cells from 85 patients undergoing in-vitro fertilization were cultured to investigate the impact of different stimulation protocols on in-vitro steroid secretion. A luteinizing hormone-releasing hormone analogue (LHRHa) was used either in the long protocol (pituitary desensitization) or in the short, 'flare up' regime. The steroidogenesis of granulosa cell cultures was investigated under basal conditions as well as after stimulation with luteinizing hormone (LH). The results were compared to the secretory capacity of cells obtained after treatment with gonadotrophins only. No correlation was found between the preovulatory oestradiol peak and subsequent in-vitro progesterone production. Granulosa-luteal cells from long protocol cycles exhibited lower progesterone production on day 2 after follicular aspiration. On days 3 and 4 there was no difference between the three stimulation protocols regarding either basal or stimulated progesterone secretion. Cells from poor responders produced significantly (P less than 0.05) less basal progesterone during culture but they responded sufficiently to an LH stimulus. Granulosa cells from polycystic ovaries showed the lowest basal progesterone secretion (P less than 0.01 versus control); however, a normal stimulated level was achieved by adding LH to the culture medium. It is concluded that long protocol LHRHa pretreatment affects the very early progesterone formation of granulosa-luteal cells. Based on these in-vitro results, both poor responders and patients with polycystic ovaries should be supported vigorously in the luteal phase. PMID- 1639974 TI - In-vitro fertilization and the ovarian hyperstimulation syndrome. AB - Eight patients who developed severe ovarian hyperstimulation syndrome (OHSS) were identified among 1302 patients undergoing in-vitro fertilization (IVF) over a 1 year period (prevalence of 0.6%); 63% had ultrasonically diagnosed polycystic ovaries (PCO) and 75% were undergoing their first attempt at IVF. Pretreatment with a superactive luteinizing hormone-releasing hormone (LHRH) analogue significantly increased the prevalence of severe OHSS (1.1% versus 0.2%, P less than 0.05) compared with ovarian stimulation with clomiphene citrate and human menopausal gonadotrophin (HMG). The mean serum oestradiol concentration on the day of human chorionic gonadotrophin (HCG) administration was 8200 +/- 2300 pmol/l. A mean of 19.6 +/- 6.8 follicles had been aspirated and 13.1 +/- 7.7 oocytes recovered at transvaginal ultrasound-directed oocyte recovery. All patients had an embryo transfer and luteal support in the form of HCG. The clinical pregnancy rate was 88%, multiple pregnancy rate 71% and implantation rate 63.5 +/- 41.3%. In a group of seven patients who were hospitalized for moderate OHSS during the same period, peak oestradiol levels were significantly lower than in those with severe OHSS (P less than 0.05). Of the group with moderate OHSS, 57% had PCO, the clinical pregnancy rate was 100% and multiple pregnancy rate 43%. Patients with ultrasound-diagnosed PCO have an increased risk of developing OHSS and the dose of HMG administered to them should be minimized. In patients at risk of developing OHSS, progesterone instead of HCG should be used for luteal support. Transfer of a maximum of two embryos or freezing all embryos for transfer in a subsequent cycle may reduce the likelihood of multiple pregnancy. PMID- 1639975 TI - Treatment with mifepristone (RU486) and oestradiol facilitates the development of genital septic disease after copulation in female rats. AB - Ovariectomized female rats were treated with oestradiol and the progesterone antagonist mifepristone. They allowed males to copulate to a similar extent as ovariectomized rats treated with oestradiol alone. The additional treatment with mifepristone, however, resulted in uterine infections following copulation, together with the prolonged presence of copulatory plugs in the uterine lumen. On several occasions rats became severely ill during the days after copulatory tests, occasionally with lethal consequences. Microscopic examination of the cervix and uterus 1 day after a copulation test in rats treated with oestradiol plus mifepristone, showed that copulatory plugs passed through the cervical canals directly into the uterine lumen. Bacterial infections and local destruction of the uterine epithelium were found in all rats examined. These features were not found in rats treated with oestradiol alone. Actions of mifepristone on the cervix of oestradiol treated rats are likely to play a key role in the passage of copulatory plugs and, thereafter, the development of uterine sepsis. PMID- 1639976 TI - Simultaneous induction of multiple follicular development with gonadotrophins and steroid replacement for in-vitro fertilization. AB - Simultaneous administration of follicle stimulating hormone, oestradiol valerate and progesterone was employed in a patient with a possible enzymatic deficiency involving low production of oestradiol. The patient became pregnant after in vitro fertilization. This case demonstrates that this treatment is useful in women with low oestradiol production and subsequent inadequate endometrial development; it also illustrates the role of oestradiol in follicular development and questions the importance of serum oestradiol measurements in the monitoring of ovulation induction. PMID- 1639977 TI - Do women want a once-a-month pill? AB - The attitudes of women of reproductive age in Scotland, Romania and Slovenia to the idea of a contraceptive pill which is taken only once each month or only when menses are delayed was investigated. In all three centres, the great majority of women felt positive towards the idea of a once-a-month pill which inhibited ovulation and greater than 50% found a pill which inhibited or interfered with implantation an acceptable idea. Only 24% of women in Scotland were attracted to the idea of a pill which was taken only if menstruation was delayed by 1 or 2 days, that is a pill which would cause an abortion, while in contrast 58% of women in Slovenia and 80% in Romania thought that such a method of controlling fertility would be acceptable. Attitudes were not related to age, social class or marital status but were influenced by religious belief and in Scotland by a history of abortion. In countries where the availability of contraception is limited and abortion is common, women would seem to welcome another method of fertility regulation--even one which disrupts the very early stages of pregnancy. PMID- 1639978 TI - Microbial colonization and sperm--mucus interaction: results in 1000 infertile couples. AB - After screening a large series of infertile patients (n = 1000 couples), potentially pathogenic microorganisms were identified in genital secretions of the majority of couples. None of the patients displayed signs or symptoms of infection of the lower genital tract. In semen specimens and cervical swabs, mycoplasmas were found in 18 and 12%, potentially pathogenic aerobic bacteria in 50 and 31%, additionally commensal aerobes in 38% and 25%, respectively. The microbial pattern showed great variability with polymicrobial growth most common. The rate of cultures positive for potentially pathogenic anaerobes was markedly influenced by the transport conditions. In endocervical material, Herpes simplex virus (HSV) was identified in 4.5%. Yeasts were found in the posterior vaginal fornix in 10%. Concerning both partners, there were only 10 couples (1%) from whom microorganisms in genital secretions could not be isolated, not including lactobacilli in females. This high prevalence of microbes and the low number of leukocytes indicate colonization rather than infection. When the microbial findings from both partners were analysed with regard to the outcome of sperm cervical mucus penetration testing in vitro, which was performed simultaneously, no significant correlation was found. Furthermore, microbial prevalence did not differ between couples with 'explained' and 'unexplained' infertility. The results of this study demonstrate that in patients without symptoms of genital tract infection, microbial colonization is of minor importance for sperm--mucus interaction and that extensive microbial screening should be preferentially performed in cases of poor sperm and/or mucus function. PMID- 1639979 TI - Chlamydial serology in the investigation of infertility. AB - Almost one-quarter of 100 asymptomatic men under fertility investigation had significant titres of IgA antibodies (greater than 1:8) specific for Chlamydia trachomatis in seminal plasma. No clear association was evident between the presence of these antibodies and sperm quality. In a second study, the female partners of men with consistently high serum or seminal plasma levels of chlamydia-specific IgA also exhibited a positive IgA reaction in serum without any clinical indications of the presence of an infection. In one group of men and women, antibiotic treatment for 4 weeks resulted in the disappearance of the IgA from the serum after a variable period of less than or equal to 12 weeks. The study indicates that chronic asymptomatic infections with Chlamydia trachomatis may be responsible for a large number of cases of infertility. It also implies that all men and women under investigation for infertility should be routinely screened with chlamydial serology regardless of previous history and clinical findings. PMID- 1639980 TI - Clinical complications during in-vitro fertilization treatment. AB - A questionnaire was sent to 12 large in-vitro fertilization (IVF) clinics in Nordic countries, asking about the number of clinical complications in connection with IVF treatment. The total number of cycles included was 10,125, with 7331 embryo transfers performed. Clinical complications were rare, although hyperstimulation syndrome was reported in 0.7% of the cycles started and follicle puncture complications in 0.5% of cycles. Post-operative infections were reported in 0.3% of embryo transfers. PMID- 1639981 TI - Is mild endometriosis always a disease? AB - The easy access to the pelvis via laparoscopy has led to an appreciable increase in the diagnosis of endometriosis in women with infertility or chronic pelvic pain. This could suggest a rising incidence of the disease but is probably largely related to the recently acquired ability to demonstrate minimal and mild lesions. However, estimates of the distribution of endometriosis in the female population might be unreliable due to lack of control of the variables which influence diagnosis of the disease in the initial stages. Analysis of data from prospective studies on asymptomatic women undergoing tubal sterilization reveals a markedly higher than expected frequency of endometriosis. This raises doubts on the clinical significance of the minimal lesions that are often found. The concept that initial endometriosis should always be treated to avoid worsening of the condition seems to lack a convincing rational basis and is not supported by definitive scientific evidence. Minimal/mild endometriosis could represent a temporary phase in an on-going process that usually results in cytolysis of recently implanted endometrial cells, whereas in a few immunologically 'tolerant' subjects, nodular, cystic and infiltrating lesions develop, with eventual progression to moderate and severe stages. PMID- 1639982 TI - Reliability of detection by polymerase chain reaction of the sickle cell containing region of the beta-globin gene in single human blastomeres. AB - Human preimplantation embryos at various stages of development have been analysed using the polymerase chain reaction to amplify a 680 base pair fragment of the beta-globin gene. Successful amplification was achieved more frequently with DNA from intact embryos containing between one and 11 cells, single cumulus cells, oocytes which had failed to fertilize and polar bodies than from single blastomeres disaggregated from intact embryos and treated in an identical manner. The distribution of nuclei demonstrated using the nuclear chromophore diamino phenyl-indole showed considerable inter-blastomere variation; however, no clear correlation between staining pattern and successful amplification was observed. The reason for the unreliable amplification of DNA from single blastomeres is unclear but this finding has important implications for preimplantation diagnosis of genetic disease. PMID- 1639983 TI - Characterization and cellular distribution of human spermatozoal heat shock proteins. AB - Heat shock proteins (hsp) are ubiquitous components of all living systems. They are up-regulated in response to adverse changes in the cellular environment and at least one highly conserved group (hsp 70) is associated with the development of tolerance to various physico-chemical stress inducers. Spermatozoa have highly condensed chromatin and unlike somatic cells, are consequently unable to mount a stress response. However, using a combination of gel electrophoresis and immunoblotting with hsp-specific monoclonal antibodies, we report that proteins of M(r) 95 kDa and 70-75 kDa corresponding to hsp 90, and multiple forms of hsp 70 are present in human spermatozoa. Immunohistochemistry localized hsp 90 to the neck and tail of unfixed, acrosome-intact spermatozoa. In contrast, an equatorial ring surrounding the nucleus was observed in unfixed spermatozoa, acrosome reacted with the calcium ionophore A23187. The ring was stained in cells fixed and permeabilized with ethanol, regardless of acrosomal status. Hsp 70 was an abundant surface antigen and as this protein was also abundant in seminal plasma, we believe that it may have been directly adsorbed onto the cell surface. More specific midpiece, equatorial and nuclear staining was also observed. Possible functions for spermatozoal heat shock proteins are discussed. PMID- 1639984 TI - Replacement of frozen embryos generated from epididymal spermatozoa: the first two pregnancies. AB - This report describes the first two pregnancies which occurred after cryopreservation, thawing and transfer of embryos generated using epididymal spermatozoa from men with congenital absence of the vas deferens. Of the 32 embryos that were thawed, 24 survived (75%) and were replaced in seven transfer cycles resulting in two (29%) pregnancies successfully delivered. The demonstration that excess embryos obtained with the use of epididymal spermatozoa can be safely frozen/thawed, and that their survival is not different from other embryos generated by in-vitro fertilization, represents a great advantage for the reproductive performance of men with congenital absence of the vas deferens undergoing microsurgical aspiration of epididymal spermatozoa. PMID- 1639985 TI - The age of pronucleate mouse ova influences their development in vitro and survival after freezing. AB - The influence of pronuclear age on embryo development in vitro and on survival and post-thaw development after cryopreservation was investigated. Pronucleate mouse ova were removed from the oviductal environment at three different times: 18 h after human chorionic gonadotrophin (HCG) (just after fertilization), 23 h after HCG (during DNA replication) and 28 h after HCG (just before cleavage). Control ova were either cultured in vitro or transferred in vivo without any treatment or exposed to dimethyl sulphoxide (DMSO) or 1,2-propanediol (PROH) before culture, but without cryopreservation. The effect on survival was evaluated by the development in vitro and in vivo after ultrarapid freezing in 3.5 M DMSO and after slow programmed freezing in 1.5 M PROH. In vitro, the development of control ova to blastocysts was 39, 54 and 77% per treated ovum at 18, 23 and 28 h after HCG, respectively. The survival rate was 78, 92 and 96% after ultrarapid freezing and 69, 90 and 81% after slow freezing, respectively. The subsequent rate of development to blastocysts per survived ovum was 21%, 35% and 62% after ultrarapid freezing and 38, 54 and 63% after slow freezing. In vivo, however, the pronuclear age did not influence the implantation rate or the number of living fetuses per transferred ovum, for neither the control, nor the frozen/thawed ova. The implantation rate and the numbers of living fetuses were not significantly different for frozen/thawed and control ova. In conclusion, early pronucleate mouse ova have a lower developmental capacity in vitro and a lower survival rate after freezing and thawing than pronucleate mouse ova just before cleavage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639987 TI - The use of cryopreserved aged human oocytes in a test of the fertilizing capacity of human spermatozoa. AB - The use of cryopreserved aged human oocytes in a diagnostic test of sperm fertilizing ability was evaluated. Oocytes arising from assisted conception cycles and showing no signs of fertilization 48 h post-insemination were cryopreserved by one of two methods. An ultrarapid method using dimethyl sulphoxide gave poor post-thaw results, with only 5/69 (7.2%) oocytes surviving. Oocytes frozen by a slow method using propanediol as the cryoprotectant gave better survival rates (359/594; 60%). Fertilization by donor spermatozoa of these thawed oocytes was poor (15/63; 24%) when the zona pellucida was left intact. To improve this, the zona was enzymatically removed using pronase. These zona-free oocytes were then inseminated with spermatozoa from a fertile donor or from men previously exhibiting fertilization failure in an in-vitro fertilization treatment cycle. The fertilization rate in the patient group (41/91; 45%) was significantly lower than in the donor group (16/18; 89%) (P less than 0.02). There was also a significant (P less than 0.03) reduction in the median number of pronuclei per oocyte (2.9 versus 4.5). These results show that aged oocytes can be effectively cryopreserved to establish a bank for use in a test to identify men with impaired sperm fertilizing capacity. PMID- 1639986 TI - Interdependent influence of follicular fluid oestradiol concentration and motility characteristics of spermatozoa on in-vitro fertilization results. AB - Methods are presented for an objective assessment of the quality of both gametes in an in-vitro fertilization programme. The concentrations of oestradiol and progesterone in follicles whose oocytes did or did not fertilize, were measured and assessed as potential markers of oocyte maturity. There was no difference in the mean concentrations of either steroid in follicular fluid of fertilized and unfertilized oocytes. However, a highly significant inverse correlation was observed between the oestradiol concentration in follicles of oocytes becoming fertilized and the number of spermatozoa added for fertilization (P less than 0.001). Follicular fluid concentrations of progesterone did not correlate with the number of inseminated spermatozoa. The correlation between follicular oestradiol concentrations and the number of spermatozoa needed for fertilization was then used to identify movement characteristics of spermatozoa in the culture medium which were relevant for fertilization. Sufficient numbers of spermatozoa having specific values of head cross frequency, lateral head displacement, linearity and curvilinear velocity were critical for the occurrence of fertilization in vitro. PMID- 1639988 TI - Sonographic appearance of the endometrium: the predictive value for the outcome of in-vitro fertilization in stimulated cycles. AB - We evaluated the predictive value for pregnancy of the endometrial thickness and pattern assessed by vaginal sonography on the day of human chorionic gonadotrophin (HCG) injection and the day of embryo transfer in 74 stimulated cycles for in-vitro fertilization (IVF) which were analysed prospectively. Thickness was measured from the echogenic interface of the endometrial-myometrium junction in transverse fundal sections. The distribution of endometrial pattern on the day of HCG was 19 A (poor quality) cases (25.7%) and 55 B (good quality) cases (74.3%). On the day of embryo transfer, 16 out of the 19 A cases (84%) remained as A pattern, while the remaining three cases (16%) had changed to B pattern; of the 55 B cases, 29 (53%) remained the same, while 26 cases (47%) changed to A pattern. There was no significant correlation between the endometrial pattern on the day of HCG and/or on the day of embryo transfer and the peak serum oestradiol levels, the number of preovulatory oocytes aspirated, the serum progesterone levels and oestradiol: progesterone ratio on the day of transfer. In contrast, on the day of HCG, endometrial thickness correlated with serum oestradiol levels on that day (P = 0.02). The presence of pattern A on the day of HCG was associated with a lower pregnancy rate [three out of 19 cases, (15.8%)], compared to pattern B [16 out of 55 cases, (29.1%)], although this was not statistically significant (P greater than 0.05). On the day of embryo transfer, comparable pregnancy rates between A pattern [11 out of 42 cases, (26.1%)] and B pattern [eight out of 32 cases, (25%)] were found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639989 TI - Pregnancy achieved by transferring blastocysts into endometrial stroma in mice. AB - To prevent the extra-uterine discharge of transferred embryos, we directly inserted mouse embryos into the endometrial stroma (intra-endometrial embryo transfer). A 27G injection needle was inserted near the utero-tubal junction into the endometrial stroma. After removal of the needle, a glass micropipette was inserted and one embryo was transferred with a very small amount of culture medium. To determine the feasibility of this method, the uterine lumen was flushed with phosphate-buffered saline from the tubal ends immediately after transferring blastocysts into pseudopregnant mice on day 2 and day 4. The rates of recovery of embryos from the uterine lumen were 5.0% (1/20; day 4) and 15.0% (3/20; day 2). These results suggest that a high rate of intra-endometrial embryo transfer is possible. The embryonic viability rates (number of viable grown fetuses/number of blastocysts transferred) of this method were 50.0% (28/56; day 4) and 25.0% (5/20; day 2). Living offspring were delivered from both recipients which had received embryos on day 2 and day 4 of pseudopregnancy. In human in vitro fertilization and embryo transfer, attempts have also been made to immobilize the embryos, and this method might be clinically applicable. Moreover, this method will be a good in-vivo model for studies on the mechanism of implantation. PMID- 1639990 TI - Implantation enhancement by selective assisted hatching using zona drilling of human embryos with poor prognosis. AB - Assisted hatching by zona drilling using acidic Tyrode's solution was performed during three randomized trials in 330 in-vitro fertilization patients. The trials were designed in order to study the overall effect of the procedure and whether characteristic patient [i.e. maternal age and basal levels of follicle stimulating hormone (FSH)] and embryonic features (i.e. zona pellucida thickness) are important for the decision to perform assisted hatching routinely. Couples (n = 137; Trial 1) in whom the female partner had normal basal FSH levels were randomized in a control group (without micromanipulation) and a zona drilling group (all embryos micromanipulated). The incidence of implantation (67/239; 28%) of zona-drilled embryos compared favourably with that of control embryos (49/229; 21%), but the difference was not significant. Retrospective analysis revealed that those embryos whose zonae were thicker than 15 microns were rescued. In order to test the validity of this finding, selective assisted hatching was performed on embryos with a poor prognosis in 163 other patients (Trial 2). The couples were randomized into a control group and a group in which embryos were selectively zona-drilled, based on zona thickness and other embryonic features. The rate of embryonic implantation in the selectively zona-drilled group was 25% (70/278), significantly (P less than 0.05) higher than that of control embryos (51/285; 18%). Although it was demonstrated retrospectively and prospectively that assisted hatching by zona drilling is effective in embryos with thick zonae (greater than or equal to 15 microns), patients whose embryos have thin (less than 13 microns) zonae may be jeopardized by the procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639991 TI - Pregnancy tests: a review. AB - Pregnancy tests are widely used both by the public and by healthcare professionals. All tests depend on the measurement of human chorionic gonadotrophin (HCG) in urine. Other pregnancy-specific materials have been proposed as pregnancy tests but none can better the sensitivity and convenience offered by immunoassay of HCG. Ultrasound detection is also not as sensitive as HCG measurement. The current generation of tests is based on monoclonal antibodies to the beta-subunit of HCG; these virtually eliminate the possibility of cross-reaction with pituitary luteinizing hormone (LH) and it is this feature which permits the high sensitivity. However, it is important to recognize that the 'beta-subunit' antibody reacts with both intact HCG, which is the major component in pregnancy serum, and with fragments of the beta-subunit (beta-core), which are the major form in urine. Both the blood and urine of non-pregnant subjects contain small amounts of HCG. HCG from the implanting blastocyst first appears in maternal blood around 6-8 days following fertilization; the levels rise rapidly to reach a peak at 7-10 weeks. With most current pregnancy test kits (sensitivity 25 units per litre) urine may reveal positive results 3-4 days after implantation; by 7 days (the time of the expected period) 98% will be positive. A negative result 1 week after the missed period virtually guarantees that the woman is not pregnant. With the present generation of test kits, false positive results due to interfering materials are extremely unlikely. Pregnancy tests have now reached a level of sensitivity and specificity which is unlikely to be surpassed either by better tests or alternative technology. PMID- 1639992 TI - Intravenous immunoglobulin treatment of women with multiple miscarriages. AB - Eleven women who had previously experienced four to eight unexplained fetal losses (median 6.0 fetal losses/woman) were treated in their next pregnancy with individualized doses of pooled intravenous immunoglobulins. Nine women (82%) delivered healthy infants subsequent to the treatment. Prior to treatment, the pregnant patients had a significantly (P less than 0.05) increased median level of complement C3 neodeterminants in the blood compared with a group of 33 normal first trimester pregnant women. This may be a sign of increased turnover of complement in these women. PMID- 1639993 TI - Oocyte donors: a demographic analysis of women at the University of Southern California. AB - A summary is presented of 3 years' experience with donors in an oocyte donation programme. During this interval, 50 women participated as gamete donors. All proffered their services without solicitation from the programme. Most were college-educated, working mothers. The majority stated that the primary motivation for participation was concern for others' infertility. Oocytes donors generally found the required use of parenteral medication taxing but tolerable. In most cases, injections were administered to the donor by her husband or by the female recipient. The majority of donations were performed without anonymity (66%). Cycles were performed at approximately 3-month intervals. This approach as well tolerated by donors and allowed predictable scheduling of cases. All women felt their participation was of great significance and each was willing to donate oocytes again if asked. PMID- 1639994 TI - Assessment at 1 year of the psychological consequences of having triplets. AB - The purpose of this study was to assess the psychological difficulties encountered by mothers 1 year after the birth of triplets. Twelve mothers entered the study having delivered triplets in a public hospital in Paris. Nine pregnancies had been initiated after in-vitro fertilization (IVF) or gamete intra Fallopian transfer (GIFT), two after ovarian stimulation and one was spontaneous. The method consisted of tape-recorded semi-structured interviews at the mothers' homes. At 1 year, a majority of mothers reported considerable fatigue and stress. In most cases, home help was no longer provided by social services or by relatives. A majority suffered from social isolation and had difficulties in going out because of a lack of help, and inquisitive looks and questions from other people. Most mothers said that having triplets placed a strain on the marital relationship. The relationship with the children was often disturbed. Mothers reported that it was difficult to give adequate attention to the three children at the same time. Most of them tended to become emotionally detached. Eight mothers expressed psychological difficulties and three of them were treated for depression. Families with triplets should be provided with increased help, special attention, counselling and support, either at home, in clubs or in special clinics. PMID- 1639995 TI - Centralized drug development. PMID- 1639996 TI - Dosage regimen design: pharmacodynamic considerations. AB - Pharmacokinetic methodology to define the time course of drug in an accessible biologic fluid is now well established as are models that relate concentration to effect. When steady-state conditions are not readily available to define a dose- or concentration-effect relationship, non-steady-state pharmacokinetic/pharmacodynamic models can be applied. Despite these methodologic advances, many aspects of clinical drug development and therapy do not readily lend themselves to pharmacokinetic/pharmacodynamic scrutiny. Barriers to this scrutiny include: drug assay problems or lack of an accessible biologic fluid that can be sampled to measure drug concentration; lack of a immediate pharmacologic effect in the clinic that can be related to concentration; and lack of a relationship between an immediate measurable pharmacologic effect and long term clinical benefit. In the evaluation and application of any drug, the following questions are useful: 1) what is the pharmacologic effect of interest? 2) is it a positive (benefit) or negative (risk) effect? 3) are there more than one positive or negative effects of interest? 4) how is the effect measured and can the measurement be applied reasonably in a clinical setting? 5) is the effect immediate (for example, blood pressure reduction) or long-term (for example, prevention of stroke with an antihypertensive)? 6) can the effect be usefully related to a concentration to guide dosimetry? and 6) if a concentration/effect relationship is likely, can it be defined at steady state or must non-steady state pharmacokinetic/pharmacodynamic models be constructed?(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1639997 TI - Ethnicity and ambulatory blood pressure measurement: relationship to clinic and laboratory measurements. AB - African Americans have a higher prevalence of hypertension than white Americans. Morbid consequences of hypertensive disease are greater in blacks than whites. For members of high-risk groups such as blacks, ambulatory blood pressure monitoring may be useful in supplementing casual clinic measurements to prevent misdiagnosis, better characterize the temporal topography of blood pressure responses, and improve prediction of left ventricular hypertrophy, hypertensive complications, morbidity, and mortality. In conjunction with other data, laboratory experiments showing that African Americans as a group show greater peripheral resistance and slowed natriuretic responses to behavioral stressors than whites, appear to provide insights as to why blacks generally respond better to diuretics and calcium channel blockers than to beta-adrenergic antagonists or angiotensin-converting enzyme inhibitors. It is suggested that ambulatory blood pressure monitoring and behavioral tasks in the laboratory may help predict individual responsiveness to antihypertensive agents. PMID- 1639998 TI - Ambulatory blood pressure monitoring for evaluation and management of hypertensives: effect on outcome and cost effectiveness. AB - Blood pressure monitoring of hypertensives in the ambulatory state by automated portable devices (ABPM) as compared with casual office readings (COBPM) may predict outcome with greater precision and at an overall lower cost. Prospective trials that in random fashion require evaluation and management decisions on the basis of ABPM compared with COBPM are required to determine whether the above is true. End points such as death, stroke, or myocardial infarction occur at a low frequency rate. This would require thousands of patients to be followed 5 or more years to determine if evaluation and management by ABPM compared with COBPM results in a different outcome. A much smaller population can be used if end points are changes in left ventricular mass and left ventricular ischemia, arterial wall stiffness and thickness, endogenous creatinine clearance, renal albumin excretion, antihypertensive drug requirements, and adverse reactions. Until results from such a prospective trial are available, COBPM is the method of choice for evaluation and management of hypertensives. Automated blood pressure measurement can provide useful information in special circumstances and is of value for research purposes. PMID- 1639999 TI - Variability and similarity of manual office and automated blood pressures. AB - The evaluation and management of hypertension is based on indirect blood pressures obtained in the office (COBPs) using the mercury sphygmomanometer. The usefulness of COBPs is limited by factors such as observer bias, which confound the ability to discern the true blood pressure value. Automated portable monitors have been marketed, which also measure blood pressure (ABP) indirectly throughout 24 hours, but without human intervention. Acceptance of a new device that indirectly records blood pressure depends largely on its the agreement with the established method of blood pressure measurement. This review compares the variability of blood pressures collected indirectly by standard mercury sphygmomanometer and by an auscultatory automated portable blood pressure monitor. The results indicate that blood pressure, when measured indirectly in a hypertensive patient, is quite variable. Automated blood pressures were lower and demonstrated less within-subject variability during repeated measures than COBPs. The agreement between ABPs and COBPs was better than the agreement between COBPs alone on successive visits. In addition, the mean hourly blood pressure profiles recorded throughout 24 hours by automated and manual methods from ten hypertensive patients were nearly identical. These data suggest that blood pressures measured by auscultatory automated methods are similar to and representative of those obtained manually. PMID- 1640000 TI - Clinical utility of ambulatory blood pressure monitoring in target organ complications and equipment choices. AB - Although population studies have demonstrated a relationship between casual office blood pressures and target organ events, the variability of these blood pressure measurements for individual patients has generated an interest in the role of ambulatory blood pressure monitoring for defining the presence of hypertension and assessing the response to therapy. Noninvasive devices provide fewer data than intra-arterial ambulatory blood pressure monitoring devices, but are safer. No current noninvasive device performs well during ambulation. Rigorous evaluation of these rapid proliferating electronic devices is important, as would be the case with any new antihypertensive agent. Although ambulatory blood pressure measurements correlate better with target organ damage for groups of patients than do casual office measurements, the predictability and limited data on reproducibility for individual patients does not support widespread application for routine testing for hypertensive patients. Ambulatory blood pressure monitoring should be viewed as a standard research tool for the evaluation of new cardiovascular drugs. PMID- 1640001 TI - Antihypertensive drug therapy does not perturb the circadian blood pressure pattern. AB - The literature was reviewed to determine whether failure of older antihypertensive drugs to suppress the early morning increase of blood pressure was responsible, in part, for the less than satisfactory rate of reduction in cardiovascular mortality rates in the United States. The authors found that neither the old nor the new antihypertensive drugs altered the 24-hour blood pressure curve pattern, although long-acting drugs did show continued effect at the end of the 24-hour period when compared with placebo. The efficacy of these drugs most likely lies with their blood pressure lowering and other ancillary effects and not with pattern changes. More importantly, examination of new data (1989) shows that the rate of decline in death due to diseases of the heart has exceeded that for cerebrovascular diseases. Our overall health care effort may be more successful than we thought. PMID- 1640002 TI - Pharmacokinetics of fluvastatin after single and multiple doses in normal volunteers. AB - The pharmacokinetics of fluvastatin, a potent inhibitor of hydroxymethylglutaryl CoA reductase and thus cholesterol synthesis, have been studied in 24 normal male volunteers who received [3H] fluvastatin in three different studies: a single dose study using oral doses of 2 or 10 mg, an absolute bioavailability study using doses of 2 mg intravenously or 10 mg orally, and a multiple-dose study using 40 mg orally once daily for 6 days. Serial blood and plasma samples and complete urine and feces were collected and analyzed for total radioactivity as well as for intact fluvastatin. Fluvastatin was rapidly and almost completely (greater than 90%) absorbed from the gastrointestinal tract, although the estimated bioavailability from the 2- and 10-mg doses was only 19 to 29% because of extensive first-pass metabolism. Fluvastatin pharmacokinetics appeared to be linear over the 2- to 10-mg dose range, as indicated by dose-proportional blood levels of total radioactivity and the parent drug. Absorbed fluvastatin was completely metabolized before excretion, the biliary/fecal route being the major excretory pathway. The recovery of radioactivity after a single dose was virtually complete within 120 hours. The terminal half-lives of fluvastatin and total radioactivity averaged 0.5 to 1 hour and 55 to 71 hours, respectively, whereas the total body clearance of fluvastatin was 0.97 L/hour/kg. Repeated oral administration of 40-mg doses of [3H]fluvastatin resulted in no time-related change in pharmacokinetic characteristics, but this dose yielded greater than proportional increases in circulating levels of the parent drug, thus suggesting a saturable first-pass effect on fluvastatin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640003 TI - Big platelets in hyperlipidemic patients. AB - Both "big" platelets and hyperlipidemia are associated with increased coronary risk. This study was undertaken to search for a possible effect of various hypolipidemic drugs on big platelets. The percentage of big platelets, assessed microscopically, was measured in 66 patients who had hyperlipidemia of various types. Twenty-seven patients with hypertriglyceridemia were randomly selected to receive either fish oil or placebo in a crossover study. Another group of 39 patients with hypercholesterolemia, among them 13 with heterozygous familial hypercholesterolemia (FH), received lovastatin. The pretreatment level of big platelets was elevated, and similar in all groups: 23.3 +/- 12% versus 22 +/- 9%, in the fish oil versus placebo group, 19.1 +/- 6.3% versus 24 +/- 11% in the FH versus non-FH primary hypercholesterolemia group (reference value, 6.8 +/- 3.5%). After treatment, despite the improvement in lipoprotein profile, the percentage of big platelets did not change. The relationship between lipid reduction and big platelets is thus questionable, and necessitates further study. PMID- 1640004 TI - Sertraline does not alter steady-state concentrations or renal clearance of lithium in healthy volunteers. AB - An open-label, placebo-controlled study was conducted to determine the effects of sertraline on the steady-state levels and renal clearance of lithium in 20 healthy volunteers. Subjects received 600 mg of lithium twice daily for 9 days. On the evening of day 8, subjects received orally either placebo or 100 mg of sertraline; these were administered twice, 8 hours apart, beginning 2 hours after the evening dose of lithium. In a comparison of day 8 with day 9 (before administration of the morning doses of lithium), sertraline was associated with only a 0.01 mEq/L (1.4%) decrease in steady-state levels and a 0.11 L/hour (6.9%) increase in the renal clearance of lithium. Neither change was statistically significant relative to placebo. Four subjects were excluded from analysis because of protocol violations or laboratory abnormalities unrelated to sertraline. Seven subjects who received lithium plus sertraline experienced side effects, mainly tremors, possibly related to treatment, whereas none of those administered lithium plus placebo experienced side effects. No sertraline-related laboratory abnormalities were observed. PMID- 1640005 TI - The effects of estazolam on sleep, performance, and memory: a long-term sleep laboratory study of elderly insomniacs. AB - Insomnia, a common complaint among the elderly, is generally treated with benzodiazepines. Long-acting benzodiazepines (e.g., flurazepam) often produce daytime somnolence and performance deficits, whereas short-acting drugs (e.g., triazolam) have been associated with marked rebound insomnia and anterograde memory loss. The authors designed a pilot study to evaluate the efficacy of an intermediate-acting benzodiazepine, estazolam (e.g., ProSom), as well as its side effects. The parameters studied were sleep, daytime performance, and memory. Ten geriatric patients (greater than 60 years of age) with insomnia participated in the study. They received placebo nightly for 2 weeks (baseline), estazolam 1 mg nightly for the next 4 weeks (treatment phase), and placebo again for 2 weeks (withdrawal period). Sleep was monitored by polysomnography the first two nights of each week in a sleep laboratory. Estazolam significantly decreased sleep latency, nocturnal awakenings, and wake time after sleep onset. Total sleep time increased an average of 63 minutes the first night of treatment. Significant improvements in wake time after sleep onset and total sleep time also were observed in the fourth week of estazolam treatment. Rebound insomnia occurred on the first withdrawal night only for wake time and total sleep time. By the next night, these sleep parameters returned to baseline. Neither day-time performance nor anterograde memory was adversely affected by estazolam treatment or its withdrawal. A 1-mg dose of estazolam appears to be a safe and effective hypnotic for elderly patients with insomnia. PMID- 1640006 TI - Hair analysis of cocaine: differentiation between systemic exposure and external contamination. AB - Cocaine has been shown to accumulate in hair of admitted users. Before using this test to verify cocaine use, however, it is crucial to differentiate between systemic exposure and external contamination from being in contact with crack smoke. In the present studies, the authors document that pyrolysis of crack results in hair accumulation of cocaine, but not its benzoylecgonine metabolite, whereas after admitted cocaine use both species are detectable in hair. External contamination with crack smoke is washable, whereas systemic exposure is not. The authors suggest these two criteria to distinguish systemic exposure from external contamination. PMID- 1640007 TI - Effect of the amount of internal standard on the precision of an analytical method. AB - In an earlier published paper, a confidence interval approach was used to show that the use of a large amount of internal standard (relative to the analyte) would adversely affect the precision of the analytical method. However, the confidence intervals were not calculated correctly. The authors recalculated the confidence intervals and found that there is no effect on the precision as measured by the confidence intervals. PMID- 1640008 TI - Shaping the future profession: a new tableau for dental education. PMID- 1640009 TI - Reliability and validity of the pilot National Board Dental Examination. AB - The reliability and validity of the pilot National Board Dental Examination were examined. The results indicate that the pilot examination is a reliable test that assesses a full range of cognitive behaviors. Furthermore, the findings indicate that the pilot examination is a unidimensional test of comprehensive general dentistry. The performance of examinees on the pilot examination was found to be similar to their performance on the traditional Part II examination. These findings suggest that the restructured Part II examination will be a more reliable and valid measure of dental students' knowledge and problem-solving skills than the traditional Part II. PMID- 1640010 TI - The role of the deans and the AADS in licensure: a call for leadership and a necessity to toil on "the road less travelled". PMID- 1640011 TI - Results of the Ohio non-patient dental board examinations for 1990 and 1991. PMID- 1640012 TI - Licensure--entry-level examinations: strategies for the future. PMID- 1640013 TI - Implications of PGY-1 to the present entry-level dental licensure system. PMID- 1640014 TI - Standardized national dental clinical examinations. PMID- 1640015 TI - Licensure based upon graduation or the real issue in protecting the public. PMID- 1640016 TI - Applicants versus first-year enrollment in selected postdoctoral dental education programs. PMID- 1640017 TI - American Association of Dental Schools. 1991-92 annual proceedings. March 14, 1991--March 7, 1992. Including the proceedings of the 1992 annual session. PMID- 1640018 TI - Expression of human T-cell lymphotropic virus type-1 gene products in the short term cultured skin tissues of an adult T-cell leukemia/lymphoma patient with cutaneous manifestations. AB - Adult T-cell leukemia/lymphoma (ATLL) is recognized as a disease etiologically associated with human T lymphotropic virus type-1 (HTLV-1) infection, but, neither viral replication nor specific virus antigen expression have been detected on ATLL cells distributed in organs, including skin. To examine the latent expression of HTLV-1 in the cutaneous lesions of ATLL patients, we cultured the lesional skin tissues in vitro and applied immunofluorescence staining with mouse monoclonal antibodies Lt-4, GIN-14, and F10, which react with p40tax, p19 and gp21, respectively. We recognized HTLV-1 specific antigens on clustered ATLL cells only in the deeper dermis of the skin after 24 hrs cultivation of the lesional skin tissue from an ATLL patient in RPMI-1640 medium supplemented with 20% fetal calf serum. In the electron microscope, we observed HTLV-1 like particles, 80-140 nm in diameter with envelope and core structures, in the same tissue specimen. These findings suggest that HTLV-1 gene products may be expressed in the skin lesions of ATLL patients and involved in the pathogenesis of skin eruptions in cutaneous type ATLLs. To our knowledge, this is the first report that envisages the potency of intracutaneous HTLV-1 expression in vivo. PMID- 1640019 TI - A new animal model for contact dermatitis: the hairless guinea pig. AB - Allergic and irritant contact reactions were evaluated in the recently identified hairless guinea pig, Crl:IAF(HA)BR, a mutant from the Hartley strain. The cutaneous changes were observed macro- and microscopically. The irritant contact dermatitis was induced by croton oil, 2,4-dinitrochlorobenzene (DNCB), or anthralin. Both hairless and hairy guinea pigs developed similar reactions to these chemicals. The density of the epidermal Langerhans cells (LC) of hairless guinea pigs was significantly higher than that in the hairy strain. Allergic contact sensitization was easily induced with DNCB. Photoallergic contact sensitization was also induced with tetrachlorosalicylanilide (TCSA) but not with tribromosalicylanilide (TBS). However, by administration of cyclophosphamide before sensitization, positive photocontact responses were seen with TBS. These results indicate that hairless guinea pigs can be used as animal models for investigation of immunologic and nonimmunologic contact reactions. PMID- 1640020 TI - Immunohistochemical characterization of cellular infiltrates in epidermal tumors induced by two-stage and complete chemical carcinogenesis in mouse skin. AB - We investigated the population and pattern of the infiltrated cells in both benign and malignant epidermal tumors which were induced chemically with benzo(a)pyrene (B(a)P) in murine skin. In benign papillomas, which were evolved by a two stage carcinogenesis regimen, a slight to mild inflammatory infiltration around the tumors was observed, and cells infiltrating into the tumor nests were rarely seen. In carcinomas, which were produced by a complete carcinogenesis regimen, a dense inflammatory infiltration was observed around the tumor nests. The infiltrated cells were characterized as T-lymphocytes, macrophages, and neutrophils. Natural killer (NK) cells were found around and in the tumor nests, but their number was small. Both T-lymphocytes and macrophages were found to invade the tumor nests in squamous cell carcinoma whose duration was more than four weeks. This experimental carcinogenesis animal model allows the detailed quantitative and functional analysis of the infiltration of immunocompetent cells into epidermal tumors. PMID- 1640021 TI - Malignancy and interstitial pneumonitis as fatal complications in dermatomyositis. AB - By sending questionnaires to the major dermatological clinics in Japan, we examined the outcome and causes of death in 182 cases of dermatomyositis (DM) observed between 1983 and 1987. The mortality rate in adults was 26.7%. Associated malignancy occurred in 47 cases (25.8% of adults), and 16 of them died of neoplasms. In contrast to 43 carcinomas, only 1 patient died of lymphoma. Associated interstitial pneumonitis (IP) appeared in 31 cases. IP started simultaneously or within 6 months after the diagnosis of DM in the majority of these cases. Of the 13 fatal cases due to IP, 8 died of respiratory failure within two months of the onset of lung disease. In the malignancy group, periungual erythema was noted in a higher proportion. Raynaud's phenomenon was more frequently noted in the IP group. DM overlapped with other collagen diseases in 14 cases. PMID- 1640022 TI - Clinicopathological and immunohistochemical study of basal cell carcinoma with reference to the features of basement membrane. AB - One hundred and thirty-five cases of basal cell carcinoma (BCC) were investigated, focusing upon factors determining a postoperative prognosis. Out of the 135, nine tumors on the face recurred. All of these nine tumors were insufficiently extirpated at the initial operation, and showed micronodular or infiltrative patterns with stromal fibrosis. Dividing the degree of dermal invasion into four levels, all tumors with recurrence reached levels 3 and 4, the two deeper groups. The immunohistochemical study using anti-laminin and anti-type IV collagen antibodies showed various changes of staining pattern around tumor cell nests, such as attenuation, disruption, and thickening of basement membrane, in contrast with the normal thinly continuous staining around nontumorous control epidermis. The disruption of basement membranes was remarkable around the tumor cells showing a micronodular growth pattern, although the discontinuity of basement membrane was observed in all types of BCCs to a greater or lesser degree. Ultrastructural thickening, multiplication, or discontinuity of basement membranes were found in all 19 cases examined with a greater or lesser degree, although they were most frequently observed around the cell nests showing micronodular growth patterns. It was concluded that deep dermal and marginal invasions were the most ominous signs of recurrence of BCCs. Although the disruption of basement membranes might participate in the local aggressiveness of BCCs, especially in the tumor cells showing micronodular infiltrative growth, other factors may concern the recurrence of BCCs. PMID- 1640023 TI - Reduction of environmental mites improved atopic dermatitis patients with positive mite-patch tests. AB - During a series of studies on the involvement of house dust mite antigens in 183 cases of atopic dermatitis, we observed an improvement in two patients following the removal of mites from their environment by means of a thorough housecleaning and replacement of the mattress. Both patients manifested the typical clinical skin lesions of atopic dermatitis and had similar laboratory findings. Although the serum IgE concentrations and specific IgE to Dermatophagoides pteronyssinus and Dermatophagoides farinae were each relatively low, the results of patch tests with these antigens were positive. Thus, a regimen aimed at reducing the presence of house dust mites can produce clinical improvement in a subset of patients with atopic dermatitis who show contact hypersensitivity to mite antigens on skin testing, but negative results on IgE (RAST; radioallergosorbent technique) testing. PMID- 1640024 TI - A case of neutrophilic dermatosis (ND) complicated by cryofibrinogenemia (CFGN) and myelodysplastic syndrome (MDS). AB - A case of neutrophilic dermatosis (ND) complicated by cryofibrinogenemia (CFGN) and myelodysplastic syndrome (MDS) is reported. Although the patient presented pancytopenia, the skin lesions were compatible with those of ND from the clinical and histopathological findings. Further, immunofluorescence technique revealed cryofibrinogen (CFG) deposits on the walls of the blood vessels in the skin lesion, and a high titer of CFG components was disclosed in the patient's peripheral blood. In this case, CFGN may have been associated with MDS; hence CFG deposits probably played a role, at least in part, in the skin lesion formation. This is probably the first case of ND complicated by CFGN. And careful examination of an underlying disease is recommended in association with ND and/or CFGN. PMID- 1640025 TI - Superficial epithelioma with sebaceous differentiation. AB - In 1980, Rothko, Farmer, and Zeligman first described the disease entity "Superficial epithelioma with sebaceous differentiation" as a histologically distinct, rare, benign lesion. We report here the first Japanese case fitting this description. The patient is a 38-year-old Japanese woman, who had a small, yellow, flat-topped, well-defined plaque on her right upper eyelid. Histologically, the lesion was a multilobular, superficial, dermal tumor with numerous broad attachments to the overlying epidermis. The overall configuration was a plate-like proliferation of tumor cells with well-defined borders. The tumor cells were basically uniform basaloid cells with single or clustered sebocytes in the upper part of the tumor and multiple well differentiated sebaceous lobules in the middle and lower parts of the tumor. Multiple cystic spaces were formed in the lobules. Differential diagnosis of several tumors with sebaceous differentiation is discussed. PMID- 1640026 TI - A case of congenital trichofolliculoma. AB - A case of congenital trichofolliculoma on the right cheek of a 3-month-old boy is reported. Trichofolliculoma usually appears in middle age; it is unusual in childhood. This is the first reported case of congenital trichofolliculoma. PMID- 1640028 TI - Prevention of pneumonia by selective decontamination of the digestive tract (SDD). AB - Prevention of respiratory tract infections is only possible when the pathogenesis is known. Three types of infection can be distinguished: primary endogenous infections, caused by pathogens carried in the throat at the commencement of mechanical ventilation, generally develop early and can only be prevented by intravenous antibiotics. Secondary endogeneous infections, caused by hospital acquired pathogens, generally develop later and can be prevented by selective decontamination of the digestive tract (SDD). The GI-tract is decontaminated by oral nonabsorbable antibiotics and for oropharyngeal decontamination a sticky antibiotic ointment is used. To date 16 controlled SDD trials in intensive care have been fully published. In all except one study, the pneumonia rate decreased significantly from 40%-50% in controls to about 10% in SDD-treated patients. All studies showed a consistent reduction of ventilator days, ICU-stay and an improved outcome in SDD-treated patients. However, in only few studies did these differences reach statistical significance. Selection of resistant strains has not been observed during prolonged use of SDD. Sucralfate reduces the pneumonia rate compared to H2-blockers or antacids by not interfering with the gastric barrier. However, gastric colonization is reduced rather than eliminated and sucralfate has almost no effect on oropharyngeal or tracheal colonization. Whether sucralfate is significantly better than a placebo remains to be established. SDD is superior to sucralfate in preventing both colonization and infection. PMID- 1640027 TI - Procedures for the diagnosis of pneumonia in ICU patients. AB - The optimal technique for diagnosing nosocomial bacterial pneumonia in critically ill patients cared for in the intensive care unit remains unclear, especially in the subgroup of patients requiring mechanical ventilation. An important advance has been the development of the protected specimen brush technique. Secretions obtained using this technique and evaluated by quantitative cultures are useful in distinguishing patients with and without pneumonia. However, this procedure has important limitations in that results are not available immediately, and in that a few false negative of false positive results may occur. Bronchoalveolar lavage has been suggested to be of value in establishing the diagnosis of pneumonia, because the cells and liquid recovered can be examined microscopically immediately after the procedure and are also suitable for quantitative culture. Microscopic identification of bacteria within cells recovered by lavage may provide a sensitive and specific means for the early and rapid diagnosis of pneumonia in this setting. The lavage technique can also be conveniently incorporated into a protocol along with quantitative culture of samples obtained using the protected specimen brush. This combination will probably improve the overall accuracy of diagnosis while allowing the administration of prompt empiric antimicrobial therapy in most patients with pneumonia. PMID- 1640029 TI - Systemic and endotracheal antibiotic prophylaxis of nosocomial pneumonia in ICU. AB - Nosocomial pneumonias, especially in ventilated patients, are a continuing problem in modern medicine. Pathogens most commonly involved with these pneumonias are Enterobacteriaceae, Ps. aeruginosa and S. aureus. Several prevention measures for nosocomial pneumonia are possible such as parenteral and topical antibiotics--a very controversial issue. Several studies with parenteral antibiotics, starting as early as 1954, could not prove any benefit of parenteral antibiotics in pneumonia prevention. Topical antibiotics, starting with polymyxin or gentamicin via the endotracheal tube in the 70s, gave controversial results. In a prospective, randomized, double-blind placebo controlled study with gentamicin via the endotracheal tube in ventilated ICU patients we found no significant reduction of pneumonia rate and mortality. However, the combined approach (SDD) of oropharyngeal, gastrointestinal and parenteral use of certain antibiotics appears to give promising results in specific patient subgroups such as ventilated polytrauma patients in ICU. PMID- 1640030 TI - Systemic antibiotic treatment of nosocomial pneumonia. AB - Nosocomial pneumonia continues to represent a significant cause of morbidity and mortality in hospitalized patients. Bacteria are responsible for greater than 90% of the pneumonias, the most common isolates being aerobic Gram-negative bacilli and S. aureus. Cornerstones of treatment are intravenous antibiotics and supportive care. In the individual case the true etiology is usually unknown; therefore empiric broad spectrum treatment is commonly used based on the prevalence of local pathogens, their antibiotic sensitivity pattern and on host factors. Combination antibiotic regimens, including beta-lactams and aminoglycosides, are considered as standard therapy and are associated with clinical success rates of greater than 80%. Monotherapy with broad spectrum antibiotics, such as third generation cephalosporins, imipenem and fluoroquinolones, can be considered as equally effective in non-neutropenic patients and in the absence of P. aeruginosa infection. More active and less toxic antibiotics are still needed for problematic pathogens such as methicillin resistant S. aureus strains, multiresistant Enterobacteriaceae and Pseudomonas species. Because further improvement in morbidity and mortality may be limited with antibiotics alone, new emphasis should be placed on prevention of infection and the use of immunotherapy. PMID- 1640033 TI - Working the bugs out. Integrated pest management saves crops and the environment. PMID- 1640031 TI - Nosocomial pneumonia: epidemiology and infection control. AB - Elderly, debilitated, or critically ill patients are at high risk for hospital acquired or nosocomial respiratory tract infection. Gram-negative bacilli, Staphyloccoccus aureus, and anaerobes colonizing the oropharynx are the most frequent etiologic agents. Colonization of the oropharynx may be related to the patient's age, underlying disease, nutritional status, prior exposure to antibiotics, supine position, and gastric colonization. Nosocomial pathogens may also be acquired from the hands of hospital personnel, contaminated equipment or fluids. The absence of sensitive and specific methods for accurate diagnosis remain a concern. Despite treatment with appropriate antimicrobial therapy, there is a high mortality and morbidity. Measures for the prevention of nosocomial pneumonia should include compliance with infection control principles, appropriate use of antibiotics, proper patient position, and removal of potential sources of cross colonization. PMID- 1640032 TI - Immunological perspectives in prevention and treatment of nosocomial pneumonia. AB - The high mortality associated with current therapeutic approaches to nosocomial pneumonia has motivated consideration of newer immunologic approaches to prevention or therapy of this infection. Serotype specific vaccines, hyperimmune immunoglobulins, and monoclonal antibodies have been developed for certain problematic pathogens. Pseudomonas aeruginosa has been the major focus of this approach, and trials of hyperimmune anti-Ps. aeruginosa globulins for treatment of pneumonia are underway. Broad-spectrum, anti-lipopolysaccharide antibody preparations have also been employed for prophylaxis of nosocomial pneumonia, but to date these trials have not been successful. Finally, anticytokine antibody therapy to reduce infection-initiated inflammatory lung damage is under consideration. PMID- 1640034 TI - Factors affecting a student's choice of dietetics as a profession. AB - In order to design more effective recruitment strategies, 419 junior students in 38 coordinated dietetics programs completed self-administered questionnaires to identify factors that attracted them to the profession. The majority (43.9%) first became interested in a dietetics career while in college; 24.9% became interested before or during secondary school; and 17.7% were making a career change. Factors that most frequently led to a career in dietetics were a course in nutrition (32.9%), a friend or relative other than parent (31.0%), and a dietitian (30.3%). Students rated the opportunity to help others (95.2%) and the relationship of nutrition to health (94.0%) as characteristics of the profession that had a highly positive influence on their decision. Interests in health, disease, and health care (70.5%); teaching and health promotion (42.7%); sports and fitness (40.7%); counseling and behavior change (35.6%); and food and cooking (35.4%) were most frequently cited as influencing the choice of a dietetics career. Students were most interested in practicing dietetics as a consultant or in private practice (37.5%) or as a clinical dietitian (34.8%). New and innovative recruitment strategies should target high school and college students and pay special attention to second-career students. Interests such as health, disease, and health care and health promotion and characteristics of the profession such as the opportunity to help others attracted present dietetics students and should be emphasized in recruiting. The best marketing tools may be the practicing dietitian and a course in nutrition. PMID- 1640035 TI - Development of moral judgment and its relationship to the education and training of dietitians. AB - The purpose of this study was to compare the development of moral judgment in 171 dietetics students before and after training from internships (n = 96), coordinated undergraduate programs (n = 61), and preprofessional practice programs (n = 14). The results of the study supported the research hypothesis that greater moral development growth would occur in supervised practices that allow students more experiences promoting moral growth, such as clinical rotations with patients, peer discussions on ethical issues, and access to instructors trained in ethics. Analysis of covariance indicated differences in the posttest scores of the three groups. Student scores for the internship and the coordinated undergraduate program were significantly different. Scores of preprofessional practice program students did not differ from those of the other groups. Internship programs offered more time in clinical rotations, used trained ethicists more, and used more methods to introduce ethics into the curriculum than did the other programs. PMID- 1640036 TI - Prediction of plasma lipids in a cross-sectional sample of young women. AB - We studied 60 premenopausal women to identify the best predictors of plasma lipid levels. Eligible subjects gave one venous blood sample during menstruation, kept a 3-day food record, completed a demographic questionnaire, had their height and weight measured, and participated in a standardized physical activity interview. Dietary constituents, anthropometric measures, serum progesterone and estradiol concentrations, and leisure-time activity level were then examined for relationships to plasma lipids. Pearson correlations revealed associations among diet, adiposity, alcohol intake, and plasma lipids. Saturated fatty acid (SFA) intake was positively related to plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density-lipoprotein (HDL) cholesterol. Height and weight were significantly related to total triglycerides. Furthermore, in the multivariate analyses, dietary constituents and height or body weight explained more of the variance in plasma lipids than did physical activity level or sex hormones. The final models for each lipid are as follows: for plasma total cholesterol and LDL cholesterol, SFA intake was the only significant predictor, for HDL cholesterol, refined carbohydrate and SFA intake; and for total plasma triglycerides, body weight and crude fiber intake. PMID- 1640037 TI - Prevalence of eating disorders among dietetics students: does nutrition education make a difference? AB - Several studies have indicated that college students majoring in dietetics have more problems associated with food than do students majoring in other disciplines. If this is true, dietetics students may need more counseling and education on eating disorders, especially because many will eventually be counseling others professionally. To assess the prevalence of negative eating behaviors among college dietetics majors, surveys based on the Eating Pattern Questionnaire were distributed to college women with majors in dietetics and other selected disciplines at a medium-sized California university. Two surveys were administered 1 year apart; the first was distributed to junior and senior women only, and the second was distributed to women of all class levels. Results from the first survey revealed that the incidence of eating disorders was not greater among the dietetics majors than among the other selected majors. In fact, dietetics majors often had more positive responses to questionnaire items, which suggests that dietetics students have better eating habits and fewer eating disorders. The results of the second survey, however, indicated that dietetics majors had significantly more negative eating patterns than did students from other majors. When separated by class, junior and senior dietetics majors had significantly more positive eating habits than did freshmen dietetics majors. These findings imply that junior and senior dietetics majors may have more positive eating patterns than freshmen dietetics majors as a result of their increased exposure to nutrition information. PMID- 1640038 TI - Effects of packaging, equipment, and storage time on energy used for reheating beef stew. AB - Energy used to reheat 3 kg of a standard beef stew to 74 degrees C was measured to determine (a) the benefits of a retort pouch packaging processing system that keeps food microbially safe at room temperature compared with a system that packages food in a plastic bag that requires refrigerated storage; (b) the most economical form for reheating (in bulk in bags, in bulk out of bags, or in portions); (c) the most economical equipment for reheating (convection oven, infrared oven, microwave oven, compartment steamer, or steam-jacketed kettle); and (d) the influence of storage time (7, 28, or 85 days). Energy used for reheating the retort product was 18,883.7 British thermal units (BTU) compared with 31,035.6 BTU for the plastic bag product. Reheating in portions used 6,857 BTU; reheating in bulk out of bag used 23,419 BTU; and reheating in bulk in bag used 64,247 BTU. The order of least to greatest energy use for equipment was microwave oven, 324 BTU; infrared oven, 5,406 BTU; convection oven, 11,399 BTU; steam-jacketed kettle, 30,713 BTU; and steamer, 51,412 BTU. Storage time in the plastic bag significantly (P less than .05) affected initial product temperature and the energy required for reheating; this was not true for the retort product. Our findings indicate that microwave heating, heating in portions rather than in larger quantities, refrigerated storage of 7 days instead of 28 days, and use of retort pouch products achieve the least energy cost in reheating a product such as beef stew. PMID- 1640039 TI - Assessing the nation's diet: limitations of the food frequency questionnaire. PMID- 1640040 TI - Nutrition and cancer prevention knowledge, beliefs, attitudes, and practices: the 1987 National Health Interview Survey. AB - This article examines the nutrition and cancer prevention knowledge, beliefs, attitudes, and self-reported dietary changes of a US national probability sample. The data were drawn from the Cancer Control Supplement of the 1987 National Health Interview Survey, which was answered by 22,043 adults. Thirty-five percent of the sample reported that they had made dietary changes in the past 1 to 5 years for health reasons. Respondents reported eating more vegetables, fruit, lower-fat meats, and whole grains/fiber and less high-fat meats, fats, sweets/snacks, salty foods, refined grain products, alcohol, and dairy products. Those who did not make any dietary changes most often said the reason was that they enjoyed the food they were presently eating and did not want to make any changes. More than 90% of the sample agreed that diet and disease were related and 73% knew that diet and cancer were related, yet 44% believed there was nothing a person could do to reduce the risk of getting cancer or didn't know what could be done. In response to open-ended questions about foods that either increase or decrease cancer risk, vegetables, whole grains/fiber, fruit, and lower-fat meats were thought to decrease risk, and high-fat meats, fats, alcohol, sweets/snacks, and additives were thought to increase cancer risk. We found education and income levels to be the major demographic variables that have an impact on cancer prevention knowledge, attitudes, and beliefs. People with lower incomes and at lower educational levels should be targeted for education about cancer risk reduction. PMID- 1640041 TI - Estimates of nutrient intake from a food frequency questionnaire: the 1987 National Health Interview Survey. AB - Nutrient intake data are reported from a 60-item food frequency questionnaire administered in the 1987 National Health Interview Survey to a representative sample of US adults 18 to 99 years of age (n = 22,080). These data provide for the first time an estimate of the distribution of usual nutrient intakes in a national probability sample. For several nutrients, 10% to 25% of respondents may habitually consume substantially less than the Recommended Dietary Allowance, despite apparently adequate group means. Hispanics reported higher energy and carbohydrate intakes and a lower percentage of energy from fat than blacks or whites (35.6%, 38.4%, and 38.7% of energy from fat for Hispanics, blacks, and whites, respectively.) Whites had lower cholesterol intake than the other two groups, and blacks had a higher intake of sweets. Alcohol intake was lower among women and persons older than 65 years, but no other differences in alcohol intake emerged. Use of adjustment factors improved nutrient intake estimates from this shortened questionnaire to levels similar to those obtained from other national dietary surveys. The nutrient intake data from this research can be used to compare demographic subgroups and to describe the mean and distribution of nutrient intake. Furthermore, this research provides national reference data to investigators who use this or related questionnaires in nutrition research. PMID- 1640042 TI - What works best for worksite cholesterol education? Answers from targeted focus groups. AB - Focus group discussions are an effective way to determine the needs and interests of a target population. In August 1989, eight focus group discussions were conducted with municipal employees in Phoenix, Ariz, to determine the needs and interests of potential participants in a worksite cholesterol education program. Employees were selected for the focus groups on the basis of an initial screening that determined their motivation to change customary eating habits. Individuals categorized as "somewhat motivated" were invited to participate in the focus groups because researchers thought they would best represent the motivation level of the majority of potential participants in the cholesterol education program. The focus group participants indicated that they preferred educational formats and approaches that appealed to diverse learning styles and recognized individual differences. Several of the program features identified by the focus groups are consistent with principles of adult education, especially active participation in the learning activity. The focus group participants wanted information presented in a simple, easy-to-understand manner, and they asked for behavioral directives rather than background information or medical jargon. Release time from work and employer commitment to the program were viewed as important to the success of the program. We conclude that employees respond best to worksite wellness programs that are simple, practical, and relevant and that allow them to participate actively in the learning activity during work time. PMID- 1640043 TI - Development and use of preprinted forms and adhesive labels in medical record charting. AB - Clear delineation of specific clinical and administrative responsibilities (eg, content requirements, cost constraints) is necessary in the development, approval, and implementation of effective preprinted documentation materials. Input early in the development stage from medical record and legal department staff ensures that proposed materials will meet organizational and legal standards. The development and use of time-saving preprinted documentation materials in medical record charting by the Johns Hopkins Oncology Nutrition Service is described. We conclude that the use of preprinted materials expedites and enhances both the consistency and quality of documentation. PMID- 1640044 TI - Dietary intakes of male endurance cyclists during training and racing. PMID- 1640045 TI - Antihistamine effects and complications of supplemental vitamin C. PMID- 1640046 TI - Peer involvement in the nutrition education of college students. PMID- 1640047 TI - Computerized analysis of selected menu items: a practical tool for the university nutritionist. PMID- 1640048 TI - Eating quality of biscuits and pastry prepared at reduced fat levels. PMID- 1640049 TI - Position of The American Dietetic Association: issues in feeding the terminally ill adult. PMID- 1640050 TI - The hamster transferrin receptor contains Ser/Thr-linked oligosaccharides: use of a lectin-resistant CHO cell line to identify glycoproteins containing these linkages. AB - We recently reported that the human transferrin receptor (TfR) contains O-linked GalNAc residues [1]. To investigate whether this modification is shared by transferrin receptors in other mammals, we investigated the glycosylation of TfR in hamster cells. To facilitate our analysis the lectin-resistant Chinese hamster ovary (CHO) cell line Lec8 was used. These cells are unable to galactosylate glycoproteins, resulting in truncation of the Ser/Thr-linked oligosaccharides to a single residue of terminal alpha-linked GalNAc. This structure is bound with high affinity by the lectin Helix pomatia agglutinin (HPA). The TfR was affinity purified from Lec8 cells metabolically radiolabeled with [3H]glucosamine and the receptor was found to bind tightly to HPA-Sepharose. Treatment of the purified TfR with mild alkaline/borohydride released [3H]GalNAcitol, demonstrating the presence of O-linked GalNAc. We also found that many other unidentified [3H]glucosamine-labeled glycoproteins from Lec8 cells were bound by HPA Sepharose. The bound and unbound glycoproteins were separated by SDS/PAGE and individual species were selected for treatment with mild base/borohydride. Treatment of glycoproteins bound by HPA, but not those unbound, resulted in the release of [3H]GalNAcitol. These studies demonstrate both that the hamster TfR contains O-linked oligosaccharides and that this approach may have general utility for identifying the presence of these oligosaccharides in other glycoproteins. PMID- 1640051 TI - A rapid reliable method to use specific probes labelling polymerase chain reaction (PCR) products. AB - Polymerase chain reaction (PCR) has allowed highly sensitive detection and amplification of individual DNA sequences. To generate specific probes for genes or cDNAs that have not yet been cloned, it is often necessary to label PCR products which are then used in Southern or Northern hybridizations or for screening cDNA and genomic DNA libraries. In this paper a rapid and versatile method of using PCR products, as specific probes, is described, after digestion with EcoRI in buffer H, in the presence of PCR reaction buffer, and purification of the PCR products for avoid the interference by competition of unlabelled dCTP in the directionally random labelling. PMID- 1640052 TI - Transverse agarose pore gradient gel electrophoresis of DNA. AB - Transverse agarose pore gradient gels were prepared on GelBond in the concentration range of nominally 0.2-1.5% SeaKem GTG agarose, using density stabilization by glycerol and incorporation of a dye to define the gel concentration at each point on the pore gradient gel. The distribution of the dye was evaluated by photography, video-acquisition and digitization of the gradient mixture and by densitometry of the gel. The gel was applied to the electrophoresis of a 1-kb standard ladder of DNA fragments, using standard submarine apparatus. The method extends to agarose gel electrophoresis the benefits of semi-automated analysis of 'Ferguson curves' described in application to polyacrylamide gel by Wheeler et al. (J. Biochem. Biophys. Methods 24, 171 180). PMID- 1640053 TI - Analysis of tubulin isoforms by two-dimensional gel electrophoresis using SDS polyacrylamide gel electrophoresis in the first dimension. AB - A two-dimensional electrophoretic system using SDS-polyacrylamide gel electrophoresis (SDS-PAGE) in the first dimension and isoelectric focusing (IEF) in the second dimension was devised. In spite of its simplicity, this method could show a markedly high resolution for tubulin isoforms and moreover could classify them into alpha- or beta-tubulin as a two-dimensional profile. With this method, seven alpha- and four beta-tubulin isoforms could be detected within axoneme from Tetrahymena cilia. Moreover this method could also resolve tubulin isoforms from the rabbit brain. These results indicate that the present two dimensional gel electrophoresis is a useful tool for the electrophoretic analysis of tubulin isoforms from various sources. PMID- 1640054 TI - An optical method for the determination of platelet count in platelet samples contaminated with red blood cells. AB - We present a simple photometric method to determine the total concentration of platelets present in a sample independently of red blood cell concentration. Standard optical density curves for platelet samples ranging in concentration from 0 to 1.5 x 10(9) cells/ml and contaminated with red blood cells ranging in concentration from 0 to 0.03 x 10(9) cells/ml are determined. A study of the absorbance spectra of red blood cells and platelets suggests that by calculating the absorbance difference between two wavelengths, an estimate of red blood cell concentration can be made. Then, in the second step of this two-step method, the individual absorbance measurements at the two wavelengths are matched to the standard values determined previously to derive an estimate of platelet concentration. In a trial of 62 unknown platelet samples contaminated with red blood cells, the standard deviation for the error in platelet count was 0.16 x 10(9) cells/ml with a mean difference of 0.011 x 10(9) platelets/ml. We conclude that our method may be useful in laboratories not equipped with electronic cell counters as well as in applications such as the development of noninvasive measurements of platelet concentration in platelet transfusion packs. PMID- 1640055 TI - Quantitative PAS assay of some carbohydrate compounds and detergents. AB - A spectrophotometric method for determination of color development of glycocompounds subjected to PAS reaction was investigated with various carbohydrate compounds and related chemicals. The conditions of the oxidation with periodic acid was found to influence the amount of the colored Schiff dye produced. Mono- and di-saccharides (mannose, glucose and maltose) were PAS negative. Glycogen was more reactive than dextran. When glycogen was hydrolyzed by amylase the intensity of the PAS product dropped until a certain limit probably reflecting the limit dextrin. The presence of proteins (albumin) or electrolytes (NaCl) did not influence the PAS reaction. Many non-ionic detergents commonly used in membrane biology such as alkyl glycosides and gluco-methyl alkanamides were strongly PAS-positive and so was the anionic detergent SDS while the zwitterionic detergents tested, such as CHAPS and CHAPSO, were PAS-negative. The color development of the spectrophotometric PAS reaction showed linearity with the concentration of a simple glycoprotein solution (peroxidase) and a complex solution (bovine serum). By the PAS reaction it was also possible to measure the content of soluble and membrane bound carbohydrate compounds in a pellet of liver cell membranes. We find that the PAS reaction is sensitive and reliable for quantitative estimations of complex carbohydrates as well as soluble and membrane-bound carbohydrate compounds. The latter should be treated with PAS unreactive zwitterionic detergents. PMID- 1640056 TI - A novel technique for the preparation of osmotically stabilized and permeabilized cells of extremely halophilic bacteria. AB - The cells of Haloferax mediterannei were stabilized by cross-linking with 0.5% glutaraldehyde for 10 min. Such cells were found to be osmotically stable even when suspended in water. The stabilized cells could be permeabilized by treatment with chloroform without leakage of intracellular components. No significant difference in the properties of an intracellular enzyme aldolase was observed, using either cell-free extract or the osmotically stabilized and permeabilized cells. This novel technique can serve as a useful tool for studying in situ regulatory characteristics of intracellular functions in halobacteria and can also help in their re-use under more stabilized conditions for biotechnological applications. PMID- 1640057 TI - Relationship between the hydrophobic and hydrophilic molecular parameters of some monoamine oxidase inhibitory drugs, determined by means of adsorptive and reversed-phase thin-layer chromatography. AB - The absorption capacity, the specific hydrophilic surface area, the lipophilicity and the specific hydrophobic surface area of 17 monoamine oxidase inhibitory drugs were determined by means of adsorptive and reversed-phase thin-layer chromatography for future application of these molecular parameters in quantitative structure-activity relationship studies. Principal component analysis suggests that most of the physicochemical parameters have a different information content, and their application in the elucidation of their mode of action is therefore justified. PMID- 1640058 TI - Comparison of the Coomassie brilliant blue, bicinchoninic acid and Lowry quantitation assays, using non-glycosylated and glycosylated proteins. AB - The concentrations of several non-glycosylated and glycosylated recombinant and native proteins were determined by three widely used colorimetric methods: Coomassie brilliant blue, bicinchoninic acid and Lowry, and, for comparison, by amino acid composition analysis. The colorimetric methods gave results differing from the values derived from the amino acid analysis, in some cases by up to 60%. For the non-glycosylated recombinant proteins, the results were in relatively good agreement with each other and with the values determined on the basis of the amino acid analysis. The Coomassie blue method was strongly dependent on the hydrophobicity of the individual protein. The bicinchoninic acid method gave results closest to those of the amino acid analysis. For the glycosylated proteins, both recombinant and native, the Coomassie blue assay gave values lower, whereas the two other methods gave values higher than those determined on the basis of the amino acid analysis. The concentration of a recombinant interferon gamma receptor produced in two differently glycosylated forms was underestimated by the Coomassie blue assay and overestimated by the bicinchoninic acid and Lowry methods, while for the non-glycosylated form of the same protein, the three colorimetric methods delivered comparable values. The results suggest a potential interference of protein glycosylation with the colorimetric assays. PMID- 1640059 TI - Immunochemical quantification of procion red HE-3B used as ligand in affinity chromatography. AB - The quantification of Procion Red HE-3B used as a ligand in affinity chromatography for proteins is reported. It's based on an enzyme-linked immunosorbent assay using antibodies against the dye. Polyclonal antibodies were classically prepared after conjugation of the dye on KLH and injection into rabbits. The development of the assay was based on the competitive inhibition between hemoglobin-dye complex and free dye. The sensitivity of this method was about 1000-times higher than a classical spectrophotometric assay, and was modulated by some chemical substituents attached on the native dye. It was demonstrated that the assay was applicable to the determination of dye traces that may be released from dye affinity sorbents. Moreover, the quantification of the dye was successfully applied to proteins that are being purified from a dye affinity column. PMID- 1640060 TI - A sensitive and rapid in situ immunoassay to quantitatively determine the cellular antigens in intact cultured cells. AB - A sensitive and rapid in situ immunoassay to quantitatively determine the cellular antigens in intact cells was developed. Antigens located in plasma membrane, endosome, cytosol, lysosome or endoplasmic reticulum of cultured cells were fixed in situ and reacted with monoclonal antibodies after permeabilization of cells with saponin. The antigen-antibody complexes were quantified by colorimetric method of peroxidase-substrate reaction. Epidermal growth factor receptor, monomer of pyruvate kinase M2 and the endoplasmic reticulum-associated thyroid hormone-binding protein were easily detected from 0.5-1 x 10(4) cells by this method. Antibody as low as 10 ng/ml gave reproducible results. Using this method, the in vivo dynamic interconversion of monomer-tetramer of pyruvate kinase M2 was found to be regulated by glucose. The ligand-induced epidermal growth factor receptor through different subcellular compartments during endocytosis was easily quantified by this method. This method was also used to compare the different amounts of the endoplasmic reticulum-associated thyroid hormone-binding protein in various cultured cells. Thus, the in situ immunoassay is an easy and versatile method which can be used to study various cellular antigens and their involvement in cellular processes. PMID- 1640061 TI - Stripping interfering sugars from samples using adapted bacteria. AB - Bacteria adapted to individual sugars quickly remove targeted sugars--stripping them--from samples in which unwanted sugars interfere. Adapted bacteria are equivalent to specific reagents for removal of sugars down to bacterial Km values, micromolar to submicromolar concentrations. Bacterial stripping is a simple method, useful when background sugars in micro-to millimolar concentrations (or larger) interfere with analysis of sought-for sugars. Bacteria such as Escherichia coli and Klebsiella are easily adapted to individual sugars such as lactose, fructose, etc., by growing the bacteria on them. Hence one can easily create (and store) many kinds of cells ready to sponge up or strip out unwanted compounds. E. coli specifically remove several sugars from samples containing 100-500 nmol of sugars, using 1-5 mg of adapted cells, and 25 degrees C temperatures. Stripping requires 1-5 min and consists of mixing cells and sample, spinning down the cells, and withdrawal of stripped supernate. A 1-5 min interval is adequate for uptake and stripping, but far too short for cells to metabolize the sugars that were taken up. Hence the cells do not leak metabolites, but act as specific adsorbants without injection of appreciable byproducts into the sample. PMID- 1640062 TI - [Sterile corneal ulcers in dry eye. Incidence and factors of occurrence]. AB - Sterile corneal ulceration is a serious complication in patients with keratoconjunctivitis sicca. The records of 134 patients, 19 males and 115 females, who presented with dry eyes in the Ophthalmologic Clinic were reviewed. Over a period of 6 years, 33 eyes of 23 (17%) patients developed a sterile corneal ulcer. The etiologies of dry eyes in these patients were: Primary Sjogren's syndrome: 10 cases, rheumatoid arthritis: 5 cases, ocular pemphigoid 6 cases, atopy: 1 case, local irradiation: 1 case. Patient's age and sex were not significantly associated with ulcer development (p greater than 0.05). The presence of a major underlying disease was the major contributing factor. Appropriate local treatment and patient compliance were also contributing factors. Blepharitis was found in 90% of patients. PMID- 1640063 TI - [Sterile corneal ulcers in dry eye. II. Treatment, complications and course]. AB - Over a period of 6 years, 23 patients (4 males and 19 females: mean age 56 years) who presented dry eyes developed 33 sterile corneal ulcers. Treatment included occlusion of the eyes or bandage soft contact lenses, prophylactic topical administration of antibiotics, punctal occlusions and currently available tear substitutes. Seventeen eyes healed completely without any corneal opacity and 10 eyes healed with opacity. Nine of the 33 eyes developed microbial keratitis. The causes of microbial keratitis were Staphylococcus aureus in 7 cases, beta hemolytic Streptococcus in one and Pseudomonas aeruginosa in one case. The microbial keratitis was treated with intensive topical antibiotics. In 6 eyes, corneal perforation occurred. Rheumatoid arthritis coexisted in four cases. PMID- 1640064 TI - [Study of the crystalline lens by fluorophotometry in 60 control subjects and 56 diabetics]. AB - Lens autofluorescence was measured with a commercially available computer fluorophotometer: Fluorotron Master, in 56 diabetic patients (34 insulin dependent and 22 non insulin-dependent) mean age +/- S.E.M. = 45.65 +/- 3.92 years; and in 60 control patients, mean age +/- 44.82 +/- 4.70 years. Scanning measurement of fluorescence was performed along the optical axis of the two eyes. Lens fluorescence refers to the highest fluorescence intensity found in the anterior part of the lens nucleus: anterior lens peak. For both populations, lens autofluorescence increased linearly with age (p less than 0.001) and was significantly higher in the diabetic population at all ages. Statistical analysis revealed a significant correlation with the duration of diabetes for insulin dependent (p less than 0.001) but not for non insulin-dependent diabetic subjects, and not on metabolic control: mean Hb A1C levels over last five years. These results showed that fluorophotometry was an objective and reproducible method for in vivo human lens study. PMID- 1640065 TI - [Juvenile serous macular detachment of the pigmented epithelium]. AB - Juvenile macular detachment of the retinal pigmented epithelium is rarely seen clinically. Single or multiple detachments can occur and are due to the accumulation of liquid in the subretinal space. The natural history of the disease, which usually affects young people, has not yet been defined. We examined and followed 19 eyes of 15 patients affected by macular juvenile serous detachment of the retinal pigment epithelium, not associated with other retinal disturbances. The patients were followed for a mean period of 12 months (range 6 33 months). The mean age was 48 years (range 40-59 years): 7 patients were male and 8 female. Mean initial visual acuity was 8/10 (range 1/10-10/10) and mean final visual acuity was 9.2/10 (range 6/10-10/10). Detachment of the retinal pigmented epithelium was unchanged in 58% of cases, decreased or disappeared in 37% of cases and increased in 5% of cases. These results indicate that the natural course is usually good and photocoagulation is not necessary. PMID- 1640066 TI - [Late macular pseudo-hole after surgical peeling of a premacular membrane]. AB - We present three clinical cases showing a pseudo macular hole that developed late after an uneventful surgical removal of an epiretinal membrane. The pseudo macular hole developed 3 to 19 months postoperatively. The macular changes seen in all cases showed stricking differences when compared with pseudo macular holes associated with epiretinal membranes. A hypothesis is suggested for the pathogenesis. PMID- 1640067 TI - [Behcet's disease disclosed by ocular conjunctival aphthous ulcer. Apropos of a case]. AB - Aphthosis in Behcet's disease is usually located in the oro-genital areas, but other locations have been described. The authors report the case of a 45 year old woman who presented with an ocular conjunctival aphthous ulcer. This was the initial presentation of Behcet's disease. This case report illustrates that aphthosis in Behcet's disease can have unusual sites such as the ocular conjunctiva. Furthermore, in this case, the conjunctival aphthosis was presenting sign of this systemic disease. PMID- 1640069 TI - [Repair of palpebral substance loss by the technique of tarsomarginal graft]. PMID- 1640068 TI - [Viscoelastic solutions for intraocular surgical use. Application in surgery of the anterior segment of the eye]. PMID- 1640070 TI - [Pilomatrixoma of the eyelid. Apropos of a case]. AB - Primary adnexal tumors of the eyelids are quite uncommon. This diagnosis should be considered in the case of a sub-epidermal tumor. We report the case of a 25 year-old female patient presenting with a left eyelid nodular tumor, which appeared clinically as a whitish swelling of the lateral part of the eyelid, covered by normal epidermis. Ultrasonography showed a heterogeneous structure probably containing calcified areas. Complete surgical removal was performed under local anesthesia. Macroscopically, the tumor was encapsulated, with an irregular surface, and it appeared stony under section. Microscopically, it was characteristic of a pilomatrixoma, with sheets of mummified cells devoid of nuclei, either clear or basophilic, and partially calcified. Neither granulomatous reaction nor ossification were observed. This clinicopathological report recalls that pilomatrixoma may appear as a single nodular tumor of the eyelid. PMID- 1640071 TI - [Programmed replacement of lenses: prevention of complications from contact lenses?]. PMID- 1640072 TI - [Surgical decompression of the optic nerve in intracanal injuries. Indications and results]. AB - Fifteen patients with traumatic optic neuropathy (anatomical section excluded) underwent surgical anterior decompression of the optic nerve, via the trans ethmoid-sphenoid approach. Improvement of visual function assessed by visual acuity and visual field measurements, was obtained in 10 patients. Results remained stable for a follow-up period of at least 6 months. There was a delay of several weeks before improvement in some of the patients. Thus a long follow-up period seems recommended. Trans ethmoid-sphenoid optic nerve decompression is a reliable procedure with low morbidity, and represents a promising therapy for indirect injuries of the optic nerve. PMID- 1640073 TI - [X-ray computed tomography in surgical indication of physiological section of the optic nerve. Apropos of 15 cases]. AB - Optic nerve trauma induces loss of vision and absence of direct pupillary light reflex. Persistence of consensual pupillary light reflex excludes anatomical section. Trans ethmoidal-sphenoidal decompression relieves the optic nerve and allows an improvement of visual function. Ten patients among 15 surgical decompressions recovered visual function. There is a good correlation between improvement and the release of an anatomical nerve compression. Recognition of direct or indirect computed tomographic signs of optic nerve compression are essential in the surgical indications. The prognosis post-surgical improvement is dependent on the sensitivity of computed tomography scan. PMID- 1640074 TI - [Exfoliative syndrome and cataract surgery]. AB - In the present prospective study, we compared the results of cataract surgery in two groups with or without exfoliation syndrome; 210 eyes were studied. The preoperative pupillary dilatation was smaller in the group with exfoliation syndrome (SE). We noticed a higher incidence of complications during planned extracapsular cataract extraction in patients with SE. A pupillary diameter smaller than 6 mm increases the incidence of capsulozonular rupture (22.5%) in these patients. After surgery, an inflammatory reaction and a transient increase in intraocular pressure were more frequent and the visual results were less favourable in the group with SE. The exfoliation syndrome is a major risk factor for cataract surgery. We recommend extracapsular extraction associated with a sector iridectomy when the pupillary diameter measures less than 6 mm. PMID- 1640075 TI - [Contrast vision in patients with aphakia and pseudophakia]. AB - A study was carried out on contrast vision in 26 aphakic patients (48 operated eyes) and 37 pseudophakic patients (37 operated eyes); in some cases an intraocular PMMA lens had been implanted, in others an IOGEL (polimacon) had been implanted. The level of sensitivity to contrast in both cases was found to be lower than expected by the Vistech company for aphakics. At the same time a comparative study was carried out of the results obtained for sharpness of vision in aphakic and pseudophakic patients, with the traditional tests of Snellen (long sightedness) and Parinaud (short sightedness) and those obtained with the Contrast Sensitivity Test System (VCTS-6500 for long sightedness and VCTS-6000 for short sightedness). The former tests were found to overestimate the visual results. Corrected aphakia was found to affect the sensitivity to contrast more than in pseudophakic cases. Nevertheless no significant differences were found between contrast vision in eyes with PMMA lens implantation and eyes with IOGEL (polimacon) lens implantation. Summing up, alterations in the sensitivity to contrast undetected by the simple measurement of visual sharpness were found. PMID- 1640076 TI - [Retinal involvement in Gaucher's disease]. AB - Gaucher's disease, a storage disease, causes storage of the sphingolipid glucosylceramide in the reticulo endothelial system. The manifestations of such deposits within the retina consist of the appearance of numerous whitish spots, such as preretinian infiltrates. Several authors have noticed the higher frequency of appearance of such spots in splenectomized patients, with marked extrasplenic infiltration. In our case, the systemic infiltration was massive at the time of the ophthalmoscopic examination, as confirmed by the bone-marrow biopsy and computerized axial tomography study, in spite of the fact that the spleen had not been removed. Our hypothesis is that the appearance of the whitish preretinian deposits in the course of the disease is connected with the degree of systemic infiltration, stressing the importance of examination of the eye fundus in Gaucher's disease. PMID- 1640077 TI - [Retinopathy in premature infants. Present value of surveillance of premature and newborn infants at risk]. AB - Systematic ophthalmologic screening of infants in a Neonatal Intensive Care Unit is time consuming and sometimes difficult. In this retrospective study of 1200 infants examined in the neonatal unit of Toulouse Regional Hospital from January 88 through December 89, we tried to summarize our findings and assess the value of systematic screening. We found 118 infants with abnormal examination: 58 preterms had retinopathy of prematurity (ROP) (5.16%) with 36 stage I, 15 stage II, 7 stage III (2 stage III+ had cryotherapy), no stage IV. Risk factors are discussed. 40 preretinal hemorrhages, all found in the first week of life. Only 2 of them persisted beyond the 2nd month (0.2%) and we found vascular anomalies that were cryotreated. 20 had various diseases. Diseases requiring early treatment were found in a general context with obvious need of ophthalmologic examination. Our study shows that 4 infants: 2 ROP III+ and 2 retinal hemorrhages or 0.4% of all infants obtained an effective benefit from this systematic screening. We confirmed the value of this screening: all infants in the neonatal care unit have at least one ophthalmologic exam, before they leave the hospital. Preterm less than 1600 g or less than 2000 g with initial resuscitation are checked during first and second month. Preterm less than 1200 g or less than 1600 g who had more than one month of oxygen therapy are checked every month until the 6th month. PMID- 1640078 TI - [Cataract surgery after injection of silicone]. AB - Thirty eyes were studied retrospectively, after cataract surgery following intraocular silicone oil injection. Cataract surgery took place before silicone oil removal in 9 eyes, at the same time as silicone oil removal in 2 eyes, and after silicone oil removal in 19 eyes. Extracapsular extraction was performed in 27 eyes, and intracapsular extraction was performed in 3 eyes. A posterior chamber intraocular lens was placed in 14 cases, and an anterior chamber intraocular lens in one case. Capsular fibrosis was observed in 19 cases, and it was treated with YAG laser in 10 eyes during follow-up. Twenty five eyes had a postoperative follow up of 3 to 37 months. Total retinal detachment occurred in 2 eyes. PMID- 1640079 TI - [Complications of disposable extended-wear contact lenses. Apropos of 6 cases]. AB - We report six cases of corneal complications observed in disposable extended-wear contact lens users: two corneal ulcers, one superficial infiltrate, two punctate keratitis with subepithelial infiltrates and one superficial punctate keratitis. In four cases a bacterial etiology was confirmed. Disposable contact lenses are not complication-free. In our series, complications were favoured or provoked by incorrect use in most cases. Other possible risk factors include poor hygiene during lens manipulation, damage to the corneal epithelium during lens exchange or lens wear, use of contaminated lubricant eyedrops, relative corneal hypoxia during overnight wear or in the case of improper fitting. Correct and adequate patient information is therefore essential to ensure that these lenses constitute a safe choice. PMID- 1640080 TI - [Congenital hypertrophy of the pigment epithelium]. PMID- 1640081 TI - [Treatment of central retinal vein occlusion]. PMID- 1640082 TI - [Implantation of a posterior chamber artificial lens sutured to the iris in the absence of the posterior capsule]. PMID- 1640083 TI - Growth, development and allometry of Philophthalmus nocturnus in the eyes of domestic chicks. AB - Fifty day-old chicks were each infected with 10 excysted metacercariae of Philophthalmus nocturnus Looss, 1907 around each orbit and growth, development and allometry were studied. The growth rate showed two phases over a period of 35 days, a limited lag phase lasting two days post-infection in which flukes did not exceed 440 microns in length, and a rapid phase during which growth was rapid and flukes reached a size of 3.008-3.504 mm on day 35. Five developmental stages were noticed during the course of development of the metacercaria to the egg-producing adult stage. Eggs appeared in the uterus on day 14 and oculate miracidia on day 25. The hindbody, testes and ovary showed positive allometric growth, the pharnyx less so, whereas negative allometric growth was shown by the forebody. Body width, oral sucker and ventral sucker were close to isometry, growing at the same rate as the body length. PMID- 1640084 TI - Effect of concurrent infection with Muellerius capillaris on the development of redial generations of Fasciola hepatica in Lymnaea truncatula. AB - The rediae of Fasciola hepatica were counted according to generation in adult and juvenile Lymnaea truncatula following single infection with Fasciola hepatica, double infection with F. hepatica and then Muellerius capillaris, or double infection with M. capillaris and F. hepatica. The rediae found in double infections were essentially first generation and an early cohort from the second generation. The following differences were observed in adult snails which underwent double infection when compared to corresponding single infections: i) dependent rediae were almost completely absent; ii) degenerating independent rediae were found in identical or decreased numbers; iii) living independent rediae of the first generation were decreased in number, while those of the second generation had variable decreased numbers. The results were similar in juvenile snails with double infections, except that the numbers of degenerating independent rediae were higher than those found in corresponding single infections and the numbers of rediae of the second generation were increased. The order of exposure in double infections had no influence on the number and maturation of fasciolid rediae. PMID- 1640085 TI - Clinical manifestations of taeniasis in Taiwan aborigines. AB - From 1974 to 1989, a total of 24,500 aborigines at 67 villages in ten mountainous districts/towns in Taiwan were examined for the Taiwan Taenia infection and 12% were found to be infected. In order to define the clinical manifestations of taeniasis caused by the Taiwan Taenia, 1661 aborigines in ten mountainous districts were surveyed. The overall clinical rate was 76%. The clinical rate was highest among Atayal aborigines (81%), followed by Bunun (66%) and Yami (61%) aborgines and lowest among Ami aborigines (40%). Among 1153 infected people, 10% had passed gravid segments in the faeces for less than 1 year, 24% for 1-3 years, 17% for 4-5 years, 23% for 6-10 years, 16% for 11-20 years, 7% for 21-30 years, and 3% over 30 years. Twenty-six occurrences of gastrointestinal and neurological symptoms were reported by 1258 infected persons. Passing proglottides in the faeces (95%) was the most frequent sign, followed by pruritus ani (77%), nausea (46%), abdominal pain (45%), dizziness (42%), increased appetite (30%), headache (26%), etc. PMID- 1640086 TI - Comparative cytotoxicity of secondary hydatid cysts, protoscoleces, and in vitro developed microcysts of Echinococcus granulosus. AB - Infection with the metacestode of Echinococcus granulosus is characterized by a concomitant immunity. Survival of established and developing hydatid cysts in the intermediate host implies a mechanism to modulate its immunological reactions. In order to investigate this mechanism, secondary hydatid cysts were isolated from intraperitoneally infected laboratory white mice (strain NMRI) 12 months p.i. A number of hydatid cysts were freed from the surrounding host adventitial tissue. Monolayer cultures of non-stimulated peritoneal macrophages of NMRI mice were prepared and incubated in the presence of the hydatid cysts. By means of a trypan blue exclusion test and by measuring the incorporation of tritium labelled uridine, it was found that the presence of hydatid cysts reduced the viability of the macrophages in vitro. Toxic substances are probably secreted since the medium of cultured hydatid cysts also displayed cytotoxic activity. Hydatid cysts with adventitia, as well as culture medium of those cysts, were less toxic. When toxins, partially purified from hydatid cyst fluid, were previously incubated on a collagen coated surface, a reduced level of toxicity was found, suggesting that collagen of the host adventitia may play a role in controlling the liberation of toxins by the hydatid cyst. Virtually no toxicity was exerted by protoscoleces or by the medium of cultured protoscoleces, in contrast to in vitro vesiculated protoscoleces (so called microcysts). The results reveal a novel feature of hydatid cysts that may play a role in the survival of the parasite in the immunized host. PMID- 1640087 TI - Differential establishment and survival of Hymenolepis diminuta in syngeneic and outbred rat strains. AB - Experimental Hymenolepis diminuta infection was carried out in inbred strains of rats (F344/N, JAR-2, LOU/M, TM, DA and DA-bg/bg) and outbred Wistar rats. All strains became infected with this cestode, but clear strain-dependent variation in the susceptibility to H. diminuta infection was observed. Marked differences in worm persistence and worm weight were found at 6 weeks post-infection in TM and DA rats. These strains would be useful to clarify the interactions between H. diminuta and its rat host. PMID- 1640088 TI - In vivo passage through calves of nematophagous fungi selected for biocontrol of parasitic nematodes. AB - The experiment was designed to test the survival and performance of stress selected nematophagous fungi after passage through the gastro-intestinal tract of cattle. Ruminating calves were fed daily with a fixed amount of fungal material grown on barley grains. The excreted dung was collected on days four and five after the start of the feeding experiment. Barley grains were washed out of the excreted dung and incoculated on water-agar plates. After incubation for one week, nine of ten fungal isolates were re-isolated from these plates. The predatory capacity of the fungi in the excreted faeces was tested in a dung pat bioassay and a faecal culture system. In the dung pat bioassay, two fungi of the genus Arthrobotrys and six of the genus Duddingtonia reduced the development of Ostertagia ostertagi third stage larvae by 85% (61%-93%), compared to the number of larvae developed from fungus-free control pats. In seven out of these eight isolates, the reduction of larvae in the faecal cultures was 92% (76%-99%). PMID- 1640089 TI - Isozymic pattern of lactate dehydrogenase in cases of bancroftian filariasis. AB - Isozymic patterns of lactate dehydrogenase (E.C. 1.1.1.27) by polyacrylamide gel electrophoresis (PAGE) were observed in various categories of filariasis and controls, i.e. asymptomatic microfilaraemia and symptomatic amicrofilaraemia, endemic normal and non-endemic normal. Lactate dehydrogenase (LDH) activity was also observed amongst the above categories of patients. An increase in enzyme activity and change in the isozymic pattern was observed in the above categories of filaria infected serum. LDH activity doubled in asymptomatic microfilaraemia whereas in symptomatic amicrofilaraemia the increase in LDH activity was thirtyfold. The isozymic pattern of microfilaraemic cases showed the presence of three bands B4, A1B3, A2B2, which are quite thick as compared to normal healthy subjects, whereas the patients with symptomatic amicrofilaraemia showed marked elevation of serum LDH-4 or A3B1. The LDH was partially purified by combined treatment of (NH4)2SO4 fractionation and gel filtration. The isozymic pattern of purified LDH showed a similar pattern. PMID- 1640090 TI - Induction of protective immunity to Brugia pahangi in jirds by drug-abbreviated infection. AB - Protective immunity of homologous challenge infection was examined in jirds after drug-abbreviated infection with Brugia pahangi. Mebendazole (MBZ) treatment at the early prepatent (5-7 weeks of post infection) or the late prepatent (7-9 weeks of post infection) period was highly effective in causing almost complete eradication of the primary infection. After challenge infection, the worm burden was significantly reduced 19% (31.1 in average) and 77% (9.5) to that of the controls (38.8 and 41.7), respectively. The magnitude of eosinophil response paralleled the degree of protection. No or only a few microfilariae were seen after challenge infection in jirds treated during the prepatent periods. They were also resistant to intravenous challenge with the microfilariae of B. pahangi. MBZ treatment at the patent period was, on the contrary, incomplete against primarily infected adult worms, and was not able to induce either significant protection (30.1 vs 33.1 in control) or eosinophil response to the challenge infection. PMID- 1640091 TI - Protease resistant interleukin-3 stimulating components in excretory and secretory products from adult worms of Strongyloides ratti. AB - Excretory and secretory (ES) products collected from adult worms of Strongyloides ratti stimulated interleukin-3 (IL-3) production with mesenteric lymph node cells from infected C57BL/6 mice, but not with normal mesenteric lymph node cells. The IL-3 stimulating components were not major IgG binding antigens. Activity of the IL-3 stimulating components was stable by treatment with protease, although reduced by heating in boiling water. PMID- 1640092 TI - Seasonal patterns in the transmission of Schistosoma haematobium in Attaouia, Morocco. AB - In the Attaouia area, the density of Bulinus truncatus (Audouin, 1827), was monitored monthly for a period of one year in correlation with weather variations. Snails were active throughout the year and particularly abundant at the end of spring and summer. Two snail generations were found to overlap. The infection rate of B. truncatus reached a maximum of 3.5% in the summer when human water contact was frequent. A selective survey conducted in the village of Lamyayha showed that the prevalence of infection with S. haematobium among the local population was 21.2% who were passing from 10 to 80 eggs per 10 ml of urine. PMID- 1640093 TI - Sites of encystment by the metacercariae of Echinoparyphium recurvatum in Lymnaea peregra. AB - Experimental infection of Echinoparyphium recurvatum von Linstow (Digenea: Echinostomatidae) cercariae in the snail second intermediate host Lymnaea peregra Muller shows that metacercarial encystment takes place on the lining of the mantle cavity, pericardial cavity and kidney lumen, with the mantle cavity the most preferred site. All three sites are accessible via the body openings. The metacercariae appear to be more susceptible to encapsulation in the visceral mass than in the cavity of the mantle, pericardium and the lumen of the kidney. PMID- 1640094 TI - Allergic reactions to latex gloves. PMID- 1640095 TI - Evaluation of a mechanical/chemical infectious waste disposal system. AB - OBJECTIVES: The mechanical/chemical infectious waste disposal system (IWDS), model Z-5000 HC, manufactured by Medical SafeTEC Inc. (Indianapolis, Indiana) was evaluated for its ability to disinfect biomedical waste. METHODS: The IWDS was operated with a sodium hypochlorite solution and tested with loads consisting of microbial cultures and blood. During and after processing, samples of liquid, milled solid waste, and leachate were collected to determine the efficacy of disinfection and the chemical by-products released. An inactivation factor was calculated. Aerosol emission was studied. All tests were done in triplicate. RESULTS: Our results showed the expected level of disinfection (inactivation factor greater than or equal to 5 log10) for all tests carried out with Bacillus subtilis, Enterococcus faecalis, Candida albicans, and Serratia marcescens, and for most of the tests with Mycobacterium fortuitum and bacteriophages OX174 and f2. Further tests performed in the absence of blood resulted in an inactivation factor greater than or equal to 5 log10 for all tests with M fortuitum, but not for those of the milled solids with bacteriophage f2. Aerosols were found to escape the apparatus when the IWDS was operated in the absence of chlorine. The liquid effluent contained an average of 17,600, and 15 mg/l of free chlorine, chloramines, and trihalomethanes (THM), respectively. The air effluent contained 1.1 mg/m3 of total chlorine and 1.4 micrograms/m3 of THM. CONCLUSIONS: Under our study conditions and except for certain tests with bacteriophage f2, the IWDS reduced the microbial populations tested by a factor of 5 log10. The aerosol dispersion problem remains to be solved, and the significance of the chemical by products released will require further investigation. PMID- 1640096 TI - Delayed detection of an increase in resistant Acinetobacter at a Detroit hospital. AB - OBJECTIVE: To study an increase of antimicrobial-resistant Acinetobacter baumannii and to assess reasons for the delayed detection of this increase. DESIGN: Review of medical, laboratory, and infection control records. Plasmid profile analysis of available A baumannii isolates. SETTING: A 340-bed trauma and intensive care hospital in Detroit, Michigan. RESULTS: The number of hospitalized patients with resistant A baumannii increased during late 1989 and early 1990: 4 in September, 10 in October, 12 in November, 18 in December, and 23 in January (chi square for trend = 14.6, p = .0001). Forty-four (66%) of the 67 patients culture-positive for resistant A baumannii had respiratory tract colonization or infection. Of 11 resistant isolates, 6 had a similar plasmid profile and 5 had no plasmids. Under the hospital's targeted surveillance system, only positive cultures from blood or wounds were investigated; this largely respiratory increase of resistant A baumannii went unrecognized until January 1990. CONCLUSIONS: Antimicrobial resistance in A baumannii is an important concern. Such resistance is not necessarily plasmid mediated. Targeted surveillance for this and other agents of nosocomial infection should be used with caution, particularly in hospitals with many debilitated patients. PMID- 1640097 TI - Epidemiology of measles immunity in a population of healthcare workers. AB - OBJECTIVE: To evaluate epidemiologic factors that can be used to predict lack of measles immunity in healthcare workers. DESIGN: During mandatory screening of employees for measles antibody, a questionnaire was used to collect demographic information. SETTING: Inpatient hospital, acute care clinics, and skilled nursing facility of a health maintenance organization. PARTICIPANTS: Employees of all ages and occupations. RESULTS: Measles immunity could not be predicted from history of measles disease and vaccination, gender, or birthplace. Of nonimmune employees, 63.7% were in the 20- to 29-year-old age group and 26.5% were in the 30- to 39-year-old age group. CONCLUSIONS: Age is the most clinically significant predictor of measles antibody, especially in persons born after 1950, who make up a large group susceptible to measles. PMID- 1640098 TI - Applying a standard of care to the quality assessment of bacteremia. AB - OBJECTIVE: To identify an indicator of appropriate antibiotic use for bacteremia that is scientifically sound, that is noncontroversial, and that can be broadly applied as an index of the quality of care. DESIGN: Retrospective review of consecutive cases of significant documented bacteremias. SETTING: Suburban tertiary-care hospital. RESULTS: Two hundred ninety-one of 300 (97%) patients received appropriate antibiotics within 48 hours after the final antibiotic sensitivity report was placed on the hospital chart. Therapy was not appropriate in 6 patients with methicillin-resistant Staphylococcus aureus and in 3 patients with enterococcal bacteremia. INTERVENTIONS: Following this study, we instituted a program to prospectively monitor antibiotic use in bacteremias. During the most recent 1-year period, the infectious disease fellow or pharmacist called the attending physician to change antibiotics in 84 of 731 (11.5%) patients with bacteremia. The program was well-accepted by attending physicians. CONCLUSIONS: A scientifically sound, non-controversial standard of care was identified and used to evaluate the appropriateness of antibiotic use. When this standard was applied prospectively and incorporated into the hospital's routine operations, the quality of care was improved. PMID- 1640099 TI - The OSHA bloodborne hazard standard. PMID- 1640100 TI - Aspects of truth: statistics, bias, and confounding. PMID- 1640101 TI - Scabies in long-term care facilities. PMID- 1640102 TI - AIDS: is it an ill wind? PMID- 1640103 TI - When your patient complains. AB - A caregiver's attitude and mood sets the tone for the interpersonal environment in which patients and caregivers relate. Caregivers should role model a positive attitude. When complaints are expressed, the caregiver should listen and make careful note not only of the content of what is expressed but the feelings behind the message. The caregiver should assess the meaning behind the complaint in order to be able to appropriately receive, investigate, and respond to complaints. It is the wise caregiver who accepts that complaints are an inevitable part of the care setting and works to develop expertise in ways of handling this human patient reaction. PMID- 1640104 TI - Parameters affecting the adsorption of ligands to polyvinyl chloride plates in enzyme immunoassays. AB - In the present work, we studied the efficacy of three blocking agents (HSA, BSA and OVA) in the inhibition of non-specific binding to PVC plates. According to the inhibition data, 1% OVA was the most effective blocking agent. On the other hand, the presence of detergents in all of the blocking solutions drastically decreased the percent inhibition of the non-specific binding. Furthermore, the effect of ligand concentration on adsorption and the kinetics of ligand adsorption to PVC plates were also investigated. Ligand adsorption is a linear function of input up to a limit (around 8.70 ng/mm2) where saturation is reached. The rate of adsorption of pure human IgG to PVC plates was proportionally increased with the temperature, as shown by proportional rate constants almost 2 times faster at 37 degrees C than at 4 degrees C. These results have practical implications for investigators using PVC for immunoassays and should be taken into consideration when designing such assays. PMID- 1640105 TI - Comparison of Freund's and Ribi adjuvants for inducing antibodies to the synthetic antigen (TG)-AL in rabbits. AB - Antibody responses and health parameters were compared in rabbits immunized with a synthetic polypeptide antigen, [L-Tyr,L-Glu,DL-Ala]-poly-L-lysine ((TG)-AL), in Freund's (FA) or Ribi (RA) adjuvants. Rabbits, 12 weeks old, of both sexes, were inoculated with 0.5 ml divided between two intramuscular (i.m.) sites. Eight received FA and antigen (50 micrograms); eight RA and antigen, eight PBS and antigen; four FA and PBS; four RA and PBS, and four PBS. Identical booster inoculations were made 21 days later, except that incomplete FA was substituted for complete FA. Rabbits were monitored until euthanasia and necropsy 7 weeks after the primary inoculation. Sera, obtained weekly, were analyzed for immunoglobulins using an enzyme immunoassay. Only rabbits given antigen with adjuvant produced high titered antibodies. Mean optical density values for immunoglobulin (Ig)M were greater the week after the booster in the group given FA. IgG values were similar for both adjuvant/antigen groups the week after the booster, but thereafter decreased in rabbits given RA. Antisera from rabbits given antigen with FA had greater avidity for the antigen than that from rabbits given antigen with RA, however, the difference was not significant (p greater than 0.05). Rabbits inoculated with FA and antigen had high serum creatinine kinase levels the day after inoculation, showed evidence of discomfort, and extensive granulomatous inflammation at the inoculation sites. Lesions were minimal to mild in rabbits given antigen with RA and PBS with either adjuvant. While RA did not result in adverse side effects, the IgG response to (TG)-AL with RA was transient compared to FA. PMID- 1640106 TI - Comparison of methodologies to measure human lung histamine. AB - The measurement of histamine in samples obtained from human lung is important in determining the roles of histamine and mast cells in normal and disease states. We, therefore, compared different assays for the measurement of histamine in human lung samples. Both a single isotope enzymatic assay and a radioimmunoassay (RIA) were capable of accurately measuring the low concentrations of histamine (0.05-2.0 ng/ml) normally found in bronchoalveolar lavage fluid. The RIA was also able to measure histamine levels up to 1500 ng/ml in human lung tissue samples. Moreover, the RIA measurement of high levels of histamine in lung samples compared favorably to an automated spectrofluorometric method. Unlike either the single isotope enzymatic assay or the automated spectrofluorometric assay which have effective capabilities at less than and greater than 2 ng/ml, respectively, the RIA can accurately measure histamine levels from 0.05 to 1500 ng/ml. Since the RIA is easier to perform, less costly, and has a wider range of effectiveness, this assay should prove valuable in assessing histamine levels from a variety of human lung samples, thereby, providing an avenue to elucidate the roles of histamine and mast cells in lung functions. PMID- 1640107 TI - Detection of Salmonella enteritidis in environmental samples by monoclonal antibody-based ELISA. AB - We have developed a enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody (ASCII) for the detection of Salmonella enteritidis in environmental samples. ELISA was used to test for sensitivity and specificity of ASCII. 38 other species of bacteria, including 31 Salmonella species were included in cross reactivity testing with ELISA. ASCII showed no reactivity with any other species tested. ASCII was found to be an IgG1 specific for S. enteritidis lipopolysaccharide (LPS). The lower limits for S. enteritidis detection was 10(5) cells/ml for pure cultures and in 10% sludge (w/v). Environmental samples (raw wastewater, wastewater effluents, mixed liquor and aerobically digested sludge) were obtained twice from five sites and ELISA tested for the presence of S. enteritidis. ELISA results compared to the American Public Health Association (APHA) method of Salmonella detection were not significantly different (P greater than 0.05). The ELISA took 24 h for completion compared to 96-120 h for the APHA procedure. Results demonstrate the reliability of the ELISA and, more importantly, provides a rapid means of detection of S. enteritidis in environmental samples. PMID- 1640108 TI - Evaluation of a flow cytometric model for monitoring HIV antigen expression in vitro. AB - Using flow cytometry, monoclonal antibodies to the HIV proteins p24, gp41 and p17 were evaluated for their ability to detect HIV antigens associated with HIV infected T cells. Mixtures containing varying ratios of HIV-infected and uninfected cells were subjected to analysis with these monoclonal antibodies. In most cases, the monoclonal antibodies identified the correct ratio of HIV infected cells to uninfected cells in the mixtures tested. An HIV anti-p24 monoclonal antibody was selected for further studies. Flow cytometric analysis was performed on various populations of cells including uninfected, acutely infected and chronically infected cells. Based on cell population fluorescence intensity three distinct regions were identified. In the first region were cells having low level fluorescence that were considered negative for HIV antigens, a profile detected in uninfected cells, and in the majority of cells in the first days following acute HIV infection. In the second region were those cells exhibiting strong fluorescence such as chronically infected cells or acutely infected cells several days after infection. A third region was identified containing cells that were intermediate in fluorescence intensity. Cells exhibiting intermediate intensity fluorescence appeared to have low concentrations of HIV p24 antigen associated with them either through viral adsorption and uptake or through low level virus expression. These intermediate region cells appeared in the early stages following acute infection, and also when chronically infected cells and uninfected cells were permeabilized together, suggesting a 'leaching' of HIV proteins from highly infected cells to uninfected cells. This leaching type of phenomenon could present problems in determining gating parameters for positive cells since uninfected cells that have associated HIV antigens exhibit higher fluorescence intensity than uninfected cells. PMID- 1640109 TI - Detection of mycoplasma contamination through modulation (stimulation or inhibition) of thymidine incorporation by unstimulated mouse spleen cells. AB - In the present report we describe a rapid and sensitive assay for mycoplasma detection in cell cultures. The assay is based on the ability of contaminated culture supernatants to modulate [3H]TdR incorporation by unstimulated mouse splenocytes. Several mycoplasma species (Mycoplasma orale, culturable and non culturable strains of Mycoplasma hyorhinis) inhibited [3H]TdR incorporation and permitted the detection of some contaminated cell cultures that would otherwise have escaped detection in assays measuring [3H]TdR incorporation by mitogen stimulated splenocytes. On the other hand, several other mycoplasma species (Mycoplasma arginini, Mycoplasma hominis) strongly enhanced [3H]TdR incorporation by unstimulated splenocytes. This enhancement was optimally detectable on day 2 after initiation of the cultures. The sensitivity of the assay was determined for a mycoplasma species (culturable M. hyorhinis) that inhibited as well as for one (M. arginini) that enhanced [3H]TdR incorporation. In both cases, the sensitivity was such that 1-3 x 10(2) mycoplasma colony-forming units (CFU) could be detected. PMID- 1640110 TI - Chimaeric protein A/protein G and protein G/alkaline phosphatase as reporter molecules. AB - The IgG binding domains of staphylococcal protein A and streptococcal protein G were expressed as a chimaera using the pGEX vector which has been advocated because its fusion proteins tend to be soluble and easily isolated on immobilised glutathione. This chimaera was soluble and abundant (yield = 18 mg/l of bacterial culture) and was tested by double diffusion in agarose and by ELISA. It was found to bind IgG of all species that either parent could bind. It was superior to protein A or protein G in binding mouse Ig. A chimaera of protein G and alkaline phosphatase was also constructed and found to be soluble and abundant (yield = 20 mg/l of bacterial culture). This protein could be used as a secondary reagent in ELISA at 5 micrograms/ml for human, rabbit and mouse and at 25 micrograms/ml for sheep. PMID- 1640111 TI - A new approach to the generation of human or murine antibody producing hybridomas. AB - A new and very efficient method for the generation of human and murine monoclonal antibodies has been developed. The method is based on clonal expansion of single B cells in the presence of human T cell supernatant and irradiated murine thymoma helper cells. Subsequently, the clonally expanded B cells are immortalized by electric field mediated cell fusion. The high efficiency of the method permits the processing of small numbers of lymphocytes, e.g., obtained by preselection of specific B cells, small amounts of human donor material and murine PBL or lymph node cells. The method may be an alternative for the EBV-transformation technique used for the generation of human monoclonal antibodies, which immortalizes only a subset of B cells and frequently yields poorly growing or unstable cell lines. This report describes the generation of murine anti-HIV and human anti-rubella antibodies combining the clonal expansion of B cells and mini-electrofusion. PMID- 1640112 TI - Novel vectors for the expression of antibody molecules using variable regions generated by polymerase chain reaction. AB - A new family of vectors has been produced which facilitates the cloning and expression of immunoglobulin variable regions cloned by polymerase chain reaction (PCR). The vectors are designed to express the cloned variable regions joined to human constant regions and take advantage of priming in the leader sequence so that no amino acid changes will be introduced into the mature antibody molecule. Both the heavy chain and light chain vectors utilize a murine VH promoter provided with an EcoRV restriction site so that the amplified variable regions can be directly cloned into a functional promoter. For the heavy chain an NheI restriction site has been generated at the first two amino acids of CH1 and the cloned leader and variable region are fused directly to the CH1 domain of the constant region. When the leader and variable regions of the light chain were fused directly to C kappa, no expression was observed. Therefore the light chain expression vector was designed with a SalI restriction site for cloning into a splice junction 3' of the variable region; VL then is joined to C kappa by splicing. Both vectors direct the expression of functional, fully assembled immunoglobulin molecules with the expected molecular weight. Use of redundant oligomers to prime the PCR permits the cloning and expression of recombinant antibodies without any prior information as to their sequence and makes it possible to rapidly generate recombinant antibodies from any monoclonal antibody producing cell line. PMID- 1640113 TI - The issue of interferon-alpha production in hemophiliacs with HIV antibodies: a slight but significant decrease? PMID- 1640114 TI - Modulation of 2',5'-oligoadenylate synthetase in patients treated with alpha interferon: effects of dose, schedule, and route of administration. AB - The interferon (IFN)-induced intracellular enzyme 2',5'-oligoadenylate (2-5A) synthetase was measured in extracts of peripheral mononuclear cells isolated from patients receiving a 300-fold range of doses of alpha interferon (IFN-alpha). The range of enzyme induction was 2.3- to 5.7-fold. The maximum fold increase varied from individual to individual as did the dose required for maximum enzyme stimulation. The magnitude and endurance of the enzyme response was a function of IFN dose and was unrelated to the duration of treatment or number of injections or to the route of administration. The enzyme assay was a more sensitive indicator of IFN administration than was measurement of the level of circulating IFN. These results substantiate the potential of a clinical 2-5A synthetase assay for monitoring IFN treatment. PMID- 1640115 TI - Production of interferon by peripheral blood mononuclear cells from normal individuals and patients with chronic lymphocytic leukemia. AB - Peripheral blood mononuclear cells (PBMC) from normal individuals were studied to identify which cells produce alpha-interferon (IFN-alpha) in response to a virus stimulus. It was found that cells both adherent and nonadherent to plastic formed IFN-alpha after induction by any one of several viruses studied. When nonadherent cells were separated on discontinuous Percoll gradients, only the cells in the less dense Percoll fractions produced IFN, whatever the virus used. By indirect immunofluorescence with monoclonal antibodies to HLA-DR and to Leu 11b, the distribution of the HLA-DR+ cells was shown to resemble most closely that of the IFN-producing population. Elimination of these cells (by complement-mediated lysis with the same antibodies) abrogated the IFN response, but NK cells remained and thus do not produce IFN-alpha. In confirmation, elimination of the Leu 11b+ cells had no effect on the amount of IFN produced. PBMC preparations from patients with chronic lymphocytic leukemia (CLL) appeared incapable of producing IFN-alpha but were shown to contain identifiable IFN-producing cells. The low or absent IFN levels in CLL are probably due to the relative scarcity of IFN producing cells in their PBMC. PMID- 1640116 TI - Molecular cloning of a gene encoding porcine interferon-beta. AB - A gene encoding the porcine interferon-beta (poIFN-beta) was cloned from a genomic library. The sequence of a potential intronless coding region as well as 1,265 bp of the 5'- and 277 bp of the 3'-flanking regions is presented. The gene is predicted to encode a mature protein of 165 amino acids and a signal peptide of 21 amino acids. This probable poIFN-beta shows high homology (63%) with human (hu) IFN-beta at the amino acid level, but less with porcine (po) IFN-alpha 1 (32%). It contains three cysteines and three potential N-glycosylation sites. A region of the 5' flank (-116 to -159) of the gene is homologous to the IFN gene regulatory element (IRE) of the huIFN-beta gene which mediates virus inducibility. Southern blot analysis indicates that the poIFN-beta gene is present as a single copy in the porcine genome. Its expression in porcine peripheral blood leukocytes stimulated in vitro by pseudorabies virus (PRV) was demonstrated at the RNA level both by Northern blot analysis and by in situ hybridization. The latter approach in addition detected only about one IFN-beta mRNA-containing cell per 2,000 PRV-stimulated porcine leukocytes, a frequency in the same range as that for leukocytes containing IFN-alpha mRNA. PMID- 1640117 TI - Mouse recombinant interferon-beta augments the induction of macrophage cytolytic activity by interleukin-2 in vitro. AB - We investigated the augmenting effect of mouse recombinant interferon-beta (MurIFN-beta) on the induction of macrophage (M phi) cytolytic activity by interleukin-2 (IL-2). C3H/He spleen cells were cultured with various doses of recombinant (r) IL-2 and/or MurIFN-beta for 4 days, and their cytotoxic activities against syngeneic M phi were assessed by a 4-h 51Cr-release assay. Although MurIFN-beta itself induced little M phi cytolytic activity, it significantly augmented the IL-2-induced cytotoxicity against M phi. MurIFN-beta showed a dose-dependent enhancement on the induction of anti-M phi activity by IL 2 with a peak at 2,000-10,000 U/ml, and the augmenting effect of rIFN-beta was more marked on lower doses of rIL-2 than on higher doses. This augmenting effect was also observed in IFN-alpha, whereas IFN-gamma showed no influence on IL-2 induced anti-M phi activity. The phenotype analysis by depletion technique with antibody and completement showed that anti-M phi effectors induced by either rIL 2 or the combination of rIL-2 and rIFN-beta were Thy-1+, asialoGM1+, L3T4-, and Ly2-. These results suggest that IFN-alpha or IFN-beta has a synergistic effect with IL-2 on the induction of nonspecific killer cells with M phi cytolytic activity. PMID- 1640118 TI - O6-alkylguanine DNA alkyltransferase is induced by human recombinant interferon alpha A/D in mouse liver. AB - Treatment of C57Bl or BALB/C mice with human interferon-alpha A/D (HuIFN-alpha A/D) significantly increased hepatic levels of the DNA repair enzyme O6 alkylguanine DNA alkyltransferase (AT). The maximum induction was seen 24 h after a single dose of 50-100 micrograms/kg IFN-alpha A/D. No induction was observed in rat liver hepatocytes cultured in vitro. Liver AT was also induced by poly(I:C), which is a potent IFN inducer. By increasing AT levels, IFN could protect against the potentially mutagenic alkylation at guanine O6 position caused by some carcinogens. Moreover this finding suggests a link between immune response and the DNA repair system, possibly acting in concert to defend the body from potentially toxic compounds. PMID- 1640119 TI - Differential responsiveness of normal and simian virus 40-transformed human fibroblast cells to interferon-gamma. AB - The effect of interferon-gamma (IFN-gamma) on epidermal growth factor (EGF) receptor binding and the proliferation of normal and simian virus 40 (SV40) transformed human fibroblast cells was compared under identical culture conditions. IFN-gamma induced an enhancement of EGF binding to normal cells, whereas it decreased the EGF binding to SV40-transformed cells. Half-maximal enhancement occurred at 72 h after the normal cells were exposed to 10 U/ml of IFN-gamma, and maximal stimulation was obtained at about 10(2) U/ml of IFN-gamma at 72 h. On the other hand, half-maximal reduction was observed for SV40 transformed cells at less than 10 U/ml of IFN-gamma at 72 h, and maximal reduction was obtained at around 10(3) U/ml of IFN-gamma at 72 h. Scatchard analysis indicated that the number of EGF binding sites of normal and SV40 transformed cells was calculated to be 1.6 x 10(5) and 0.88 x 10(5) per cell, respectively, and was little altered by IFN-gamma treatment. The dissociation constant (Kd) of normal cells, however, decreased from 4.5 nM (control) to 2.0 nM (IFN-gamma-treated), while the Kd of SV40-transformed cells increased from 3.6 nM (control) to 17.0 nM (IFN-gamma-treated). The immunoprecipitation of 125I-labeled EGF-bound EGF receptors with anti-receptor antiserum indicated that a 72-h IFN gamma treatment did not induce a conformational alteration in the EGF receptors of both normal and transformed cells. The DNA synthesis of normal cells was enhanced by EGF, and IFN-gamma treatment potentiated the effect of EGF on DNA synthesis, probably due to the increased binding affinity of EGF to the cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640120 TI - Cloning of the cDNA for canine interferon-gamma. AB - We have taken advantage of conserved regions of cDNA sequences for interferon gamma (IFN-gamma) from other species to design polymerase chain reaction (PCR) primers capable of amplifying the protein-coding region of the canine mRNA. We report here the cDNA cloning of this region from dog lymphocytes and the cDNA sequence. The predicted amino acid sequence is also reported and compared to the known sequences of these other species. The molecular clone for the canine IFN gamma will allow direct study of this important cytokine's role in graft rejection in the widely used experimental canine transplant model. PMID- 1640121 TI - Interferon-beta treatment does not elevate cortisol in multiple sclerosis. AB - Interferons (IFN) are used to treat cancer and multiple sclerosis (MS). High doses of IFN elevate serum cortisol, which may indirectly affect the course of either of these diseases. IFN-induced elevation of serum cortisol could speed recovery from exacerbations of MS. We find that IFN-beta at 9 or 45 MU every other day does not elevate serum or urine cortisol in MS. Clinical effects of IFN beta in MS are likely to be direct, and not mediated indirectly through alteration of serum cortisol levels. PMID- 1640122 TI - Regulation of the natural killer cell response to interferon-alpha by biogenic amines. AB - Monocytes, recovered from human peripheral blood by counter-current centrifugal elutriation (CCE), suppressed baseline natural killer (NK) cell cytotoxicity (NKCC) and rendered NK cells resistant to activation of cytotoxicity by human recombinant interferon-alpha (IFN-alpha) by a cell contact-dependent mechanism. Monocyte-induced suppression of resting and IFN-activated NK cells was abrogated by the biogenic amines histamine [via H2-type receptors (H2R)] and serotonin [via 5-HT1A-type receptors (5-HT1AR)]. Our data are suggestive of a monocyte/NK cell interaction that is subject to regulation by biogenic amines. PMID- 1640123 TI - International guidelines for specialty training in oral and maxillofacial surgery. PMID- 1640124 TI - Fascia lata interpositional arthroplasty in the treatment of temporomandibular joint ankylosis caused by psoriatic arthritis. AB - A patient with bilateral temporomandibular joint ankylosis, secondary to psoriatic arthritis, was treated by interpositional arthroplasty using fascia lata autogenous grafts. Despite gross limitation of mandibular movements prior to operation, radiological and functional recovery was complete at 2 years. PMID- 1640125 TI - Titanium mesh in orbital wall reconstruction. AB - Successful use of titanium mesh sheets in the reconstruction of orbital wall defects of up to 2.5 x 2.5 cm following trauma and followed up for a mean of 24 months is demonstrated. This material is especially useful in orbital floor and medial wall blow-out fractures, and is a valuable additional material for use in maxillofacial reconstruction. PMID- 1640126 TI - Asymptomatic impacted teeth in edentulous jaws undergoing preprosthetic surgery. A long-term evaluation. AB - A long-term evaluation is made of 15 patients with asymptomatic impacted teeth in edentulous jaws. Seventeen impacted teeth in 15 patients were recorded and analysed. They were located in denture-bearing areas and in areas undergoing preprosthetic surgery. All patients, except one lost after 1-year period, were followed clinically and radiographically for 1 to 10 years with an average of 4 years. The asymptomatic impacted teeth in edentulous jaws embedded in bone or covered with mucosa did not cause any problem to the patients. The findings of this study support the view that removal of asymptomatic impacted teeth in denture-bearing areas, or in areas undergoing preprosthetic surgery, is unnecessary as long as the integrity of the covering tissues is preserved. A policy or radiological surveillance is recommended. PMID- 1640127 TI - Computer-aided individual prognoses of squamous cell carcinomas of the lips, oral cavity and oropharynx. AB - Computer-aided individual prognoses (CIP) is a software-package developed on the basis of an empirical study and can be installed on any IBM-compatible personal computer. The project which went into the making of CIP was called "Prospective DOSAK-study on squamous cell carcinomas of the lips, oral cavity and oropharynx". In the course of the study 1485 patients were treated between 1977 and 1982, and followed up through 1985. CIP facilitates individual prognoses and comparisons of independent patient groups with parallel groups from the data of the above mentioned study. In practical clinical work individual prognoses allow exact and reliable judgements on individual patients. In clinical cancer research it provides the information about prognostic factors required for controlled clinical studies. The comparison of independent patient populations allows for an ongoing qualitative control of the patients in each clinical institution. In clinical cancer research such a comparison means that certain characteristics of the patient, the tumor and of the disease can be given higher prognostic value. The same is true of the clinical testing of therapeutic measures which is typically carried out during phase-II-studies. Due to its menu-based organization CIP does not presuppose any specialist knowledge on the part of its users and can be regarded as particularly user-friendly. PMID- 1640128 TI - Intraoral cheek transposition flap for primary reconstruction of the soft palate. AB - A method for primary reconstruction of the soft palate following radical tumor resection is described. The resulting defects can be repaired with 2 layers of tissue by combination of a cranial pedicled pharyngeal flap and a cranial pedicled intraoral cheek transposition (IOCT-) flap. For additional resection of the lateral pharyngeal wall the technique can be combined with a masseter crossover flap. The method allows satisfying restoration of swallowing and speech with relatively small operative effort. PMID- 1640129 TI - Heterotopic salivary gland tissue in lymph nodes of the cervical region. AB - The occurrence and composition of intranodal salivary gland tissue (ISGT) in the head and neck region were investigated. ISGT was mainly composed of mature acini, intercalated ducts and intralobular ducts but immature acini (20.8%) and immature small ducts (18.8%) were also observed. The latter resembled salivary gland tissue in an early developmental stage. Various histological changes of ISGT were observed including cyst formation (16.7%), oncocytic metaplasia (8.3%), oncocytic adenomatous hyperplasia (8.3%) and ductal proliferation (20.8%). Thus ISGT may contain immature components with a potential for differentiation and proliferation. PMID- 1640130 TI - Bolus dose with continuous infusion of midazolam as sedation for outpatient surgery. AB - This double-blind, randomised, cross-over trial in 41 patients for 3rd molar surgery compared the safety, amnesic properties and psychomotor recovery between a bolus injection of midazolam and a bolus injection followed by continuous infusion of midazolam. The latter showed good safety and better amnesia to events during the procedure, but prolonged the recovery time. PMID- 1640131 TI - Migratory facial swelling due to gnathostomiasis. AB - Two cases of facial gnathostomiasis in female Thai patients are described. Gnathostomiasis is caused by a roundworm, Gnathostoma spinigerum. In both patients the disease was characterised by intermittent and migratory swelling of the face. At present no effective therapy is available. Surgical removal of the parasite would be a curative treatment; it is however, rarely successful due to the parasite moving relatively rapidly within the soft tissues. The disease can be prevented by avoiding undercooked meat including fish. In endemic areas such as Southeast Asia, gnathostomiasis must be considered in cases of oro-facial swelling of otherwise unknown cause. PMID- 1640132 TI - An experimental study of the osteogenicity of free periosteal allografts with cyclosporine A administration. AB - Free tibial periosteum was grafted onto the dorsum (m. cutaneous trunci) of Sprague-Dawley rats to examine its osteogenic potential. The animals were divided into 3 groups based on type of: A. autogenous periosteum, B. allogeneic periosteum and C. allogeneic periosteum, and treated with cyclosporine A immunosuppression. The osteogenic response was evaluated radiologically and histologically. This study indicates that in this model periosteal allografts with immunosuppression of the recipient result in osteogenesis. Clinical application of the technique will only be possible if immunosuppressive methods with minimal morbidity are developed so that they can be used for prolonged periods. PMID- 1640133 TI - Temporomandibular joint eminence augmentation by down-fracture and interpositional cartilage graft. A new surgical technique. PMID- 1640134 TI - Cardiac dysrhythmias complicating maxillofacial surgery. PMID- 1640135 TI - The recovery of sensation and function after cross-finger flaps for fingertip injury. AB - Over a five-year period, 54 patients had cross-finger flaps at Mount Vernon Hospital for single fingertip injuries. A retrospective study was carried out to evaluate the recovery of sensation and function. 92% of the patients were satisfied with the result although 53% suffered cold sensitivity. All the cross finger flaps tested had diminished sweating and a raised threshold for electrical stimulation. Despite the presence of protective sensation, dynamic sensory discrimination and the return of advanced A beta fibre innervation, none of the cross-finger flaps was found to have recovered tactile gnosis. PMID- 1640136 TI - Mixed sclerosing bone dystrophy presenting with upper extremity deformities. A case report and review of the literature. AB - We present a detailed study of a 59-year-old white woman with mixed sclerosing bone dystrophy: the rare occurrence of two or more sclerosing bone dysplasias in a single subject. She exhibited features of osteopoikilosis, osteopathia striata and melorheostosis. The symptoms were primarily the result of the melorheostosis lesions which were distributed within the C6 sclerotome. This is an unusual case of mixed sclerosing bone dystrophy in that the upper extremity was the main site of involvement, instead of the usual symmetrical involvement of all limbs. The patient developed a recalcitrant lateral epicondylitis in the un-involved contralateral elbow that required surgical treatment. PMID- 1640137 TI - An unusual association of the windblown hand with upper limb hypertrophy. AB - An eight-year-old boy presented with a congenital windblown hand deformity associated with partial hypertrophy of that arm. Many of the classical features of the windblown hand syndrome described in previous papers were absent. In this case, the primary cause of the ulnar-drift deformity was an anomalous epiphysis at the base of the second metacarpal. Surgical correction was readily obtained by osteotomy at the base of the metacarpal combined with soft tissue re-alignment. PMID- 1640138 TI - Magnetic resonance imaging in Kienbock's disease. AB - With a 1.5 tesla superconducting M.R. imager and surface coil, M.R. imaging achieved high resolution analysis of the wrist on five normal wrists and 26 wrists with Kienbock's disease. The purpose of this study was to establish new criteria for diagnosis, staging and prognosis of Kienbock's disease, based on signal characteristics on T1- and T2-weighted images. Focal loss of signal intensity of the lunate on T1-weighted image was an indication of Kienbock's disease. A decreased signal containing a high spot and increased signal intensity of the lunate on T2-weighted images indicated a better prognosis. After osteotomy of the radius, the signal intensity of the lunate returned to normal and Lichtman's stage II cases had better results than those in stage III. M.R. imaging is ideal for evaluating the lunate in Kienbock's disease. PMID- 1640139 TI - Anatomy, descriptive and surgical. PMID- 1640140 TI - Magnetic resonance imaging in scaphoid fractures. AB - The use of a 1.5 tesla superconducting M.R. imager and surface coil was found to enhance the ability of M.R.I. to depict the fine anatomy of the wrist. Five healthy volunteers and 28 patients with scaphoid fractures underwent M.R.I., which made possible a definitive diagnosis of scaphoid fractures at an early stage. A fresh fracture was identified by decreased or iso signal intensity on the T1-weighted image and increased signal intensity on the T2-weighted image. This increase continued until bony union was apparent on radiographs. On the T2 weighted image, high signal intensity was characteristic of fresh fractures and suggested that bony union was possible. When bony union was complete, the intensity of the signal for the scaphoid on both T1- and T2-weighted images returned to normal. M.R.I. should thus prove useful in the diagnosis of scaphoid fractures. PMID- 1640141 TI - Detecting fractures of the scaphoid: the value of comparative X-rays of the uninjured wrist. AB - Pain or tenderness in the anatomical snuff-box following trauma suggests an injury to the scaphoid or surrounding soft tissues. It is often difficult to make a definite diagnosis since normal bone markings across the scaphoid can be misinterpreted as a fracture. To clarify whether a fracture is present or not, an X-ray of the uninjured scaphoid is taken in a comparable position to the most suspicious view. If bone markings are similar on both views, then a fracture can be excluded. Conversely, if the bone markings differ, then suspicion of a fracture may be confirmed. In combination with the clinical features, a more accurate diagnosis can be made and unnecessary out-patient and X-ray reviews can be avoided. PMID- 1640142 TI - Kienbock's disease. PMID- 1640143 TI - Arthroscopy for the diagnosis of post-traumatic wrist pain. AB - 30 patients with post-traumatic wrist pain were investigated by arthroscopy. The clinical findings and type of injury were compared to the pathological morphology seen at arthroscopy. In 21 (70%) of the patients, arthroscopic findings gave a plausible explanation for the symptoms. PMID- 1640144 TI - Scapho-trapezio-trapezoid arthrodesis in the treatment of Kienbock's disease. A study of 16 cases. AB - Sixteen scapho-trapezio-trapezoid arthrodeses were performed for Kienbock's disease. In ten cases, a prosthetic replacement of the lunate was inserted at the same time. Clinical results were good with regard to pain and fair with regard to grip strength which was improved by an average of 32%. In contrast, the arc of flexion-extension was 38% less than on the unoperated side. Long-term radiographic assessment showed the efficacy of the procedure in maintaining carpal height. Biomechanical observations and a review of poor results showed the limits of the method and the importance of correct positioning of the scaphoid. We concluded that triscaphe arthrodesis was a useful procedure for the treatment of Kienbock's disease in Decoulx's stage 3. PMID- 1640145 TI - The natural history of undiagnosed wrist pain in young women. A long-term follow up. AB - 43 young women with undiagnosed wrist pain were followed up for a median of 13 years (range 3 to 19). 26% were now free of pain and 35% had improved; 30% were unchanged and 9% were worse. Overall, 40% were still significantly troubled. There was no evidence that those patients suffered or had suffered from emotional or psychiatric disturbance which might have been responsible for the pain. Only three patients had developed ganglia. PMID- 1640146 TI - Percutaneous Kirschner wire stabilisation following closed reduction of Colles' fractures. AB - 32 consecutive unstable Colles' fractures were treated by closed reduction and percutaneous Kirschner wire stabilisation through the radial styloid, followed by a below-elbow cast. Radiological assessment was made at five stages of treatment: at the time of the fracture, immediately after operation, after two weeks, after six weeks and a final review at an average period of 15.9 months. Functional assessment was made at the final review. Only three fractures developed secondary displacement, which was due to the wrong placement of the Kirschner wire. There were no complications. PMID- 1640147 TI - Pilon fractures of the wrist. Displaced intra-articular fractures of the distal radius. AB - 22 patients who sustained high energy wrist injuries are reported. These complex injuries resulted in articular disruption of the distal radius. Associated injuries included scapho-lunate dissociation (18%), central die-punch injuries (14%), ulnar fractures (41%) and diastasis at the distal radioulnar joint (23%). Nine fractures (41%) were open and almost a third of patients had other skeletal injuries. All patients were treated by external fixation and reviewed after a mean follow-up of 2 1/2 years. There were no excellent results and only ten good ones (45%). The mean functional impairment was 32%. The external fixator was effective in maintaining extra-articular alignment, but not in ensuring accurate reduction of the articular surface. Residual incongruity of the joint surface was an adverse prognostic feature. All five patients (22%) with an articular step of more than 2 mm. developed symptomatic arthritis. Failure to restore the joint line did not account for all the unsatisfactory results; persistent scapho-lunate dissociation and problems at the distal radioulnar joint were also important. PMID- 1640148 TI - Controlled study of the use of local steroid injection in the treatment of trigger finger and thumb. AB - A controlled double-blind prospective study of injection of methylprednisolone acetate plus local anaesthetic against a control injection of a local anaesthetic in the treatment of trigger finger and thumb has shown a 60% success rate for the steroid injection against 16% for the control group (p less than 0.05). This is the first controlled trial of local steroid therapy in this condition. PMID- 1640149 TI - The association between alcohol, hepatic pathology and Dupuytren's disease. AB - We have looked at the incidence of Dupuytren's disease in alcoholics, those with non-alcoholic liver disease and a control population. Both alcoholic patients and those with non-alcohol related liver disease had a higher rate (28% and 22% respectively) than the controls (8%), but this did not quite reach statistical significance (p greater than 0.05). In addition we found no Dupuytren's disease in 50 Egyptian patients with bilharzia and no consistent biochemical abnormalities in 134 patients with significant Dupuytren's disease. We conclude that alcoholics probably do have a higher rate of Dupuytren's disease and that this effect is largely due to the liver disease caused by alcohol abuse, but that the genetic factors are of greater aetiological importance. PMID- 1640150 TI - The long term result of digital nerve repair in no-man's land. AB - 30 isolated lesions of digital nerves which had been repaired by microsurgical techniques were examined in 27 patients. The average length of follow-up was 25 months (range: 12-48 months). Patients were assessed subjectively using a visual analogue scale and examined for light touch, pain, two-point discrimination, electrical conductance and sensory threshold. Although 37% of fingers regained normal two-point discrimination, only 27% of patients graded their overall result as excellent and 40% complained of persistent hyperaesthesia for up to two years. None felt that their finger had regained normal sensation. All patients undergoing digital nerve repair should be warned that hyperaesthesia may persist for several years and that an adult will never regain normal sensation. PMID- 1640151 TI - The recovery of peripheral nerves following tissue expansion. AB - A rat sciatic nerve model has been used to study the response of nerves to tissue expansion and their recovery at intervals up to 100 days using electrophysiology and histological methods. Tissue expansion has been shown to increase nerve length by 32% of which half remained at 100 days. Following tissue expansion the mean conduction velocity of the sciatic nerve was reduced to 30.0 +/- 1.35 m/s which represented 60.3% of control values, by 100 days the conduction velocity had almost returned to normal. Histological examination showed the cause of the reduction in function to be due to segmental demyelination without axonal degeneration, these changes returned towards normal during the recovery period but were not completely reversed by 100 days. PMID- 1640152 TI - The mechanical strength of various suture techniques. AB - The mechanical strengths of five techniques of tendon repair have been evaluated using human cadaver tendons. A modified Kessler repair with a peripheral circumferential suture and the method of Becker were found to require the greatest load to produce gapping, but the Becker and Savage repairs withstood the highest load before failure. PMID- 1640153 TI - A biomechanical analysis of a new interlock suture technique for flexor tendon repair. AB - Using a computerised tensometer, both the gap-producing and breaking forces of a new interlocking suture for flexor tendon repair were compared to the modified Kessler and the Strickland techniques. 30 porcine deep flexor tendons were used in each group and all repairs were performed with 3/0 polypropylene sutures. The interlock technique withstood gap-producing and breaking forces significantly better than the modified Kessler and Strickland techniques. Also, the gap producing force was closer to the breaking force with the interlock technique than with the other two techniques. PMID- 1640154 TI - The effect of constant direct electrical current on intrinsic healing in the flexor tendon in vitro. An ultrastructural study of differing attitudes in epitenon cells and tenocytes. AB - Light and electron microscopy were performed in a study of the effects of electrical stimulation upon the reparative processes in flexor tendons cultured in vitro. After one or two weeks of incubation, the unstimulated control tendons were covered with fibroblastic surface cells, thought to have originated from the epitenon. In contrast, the tendons subjected to electrical stimulation had no proliferation of the epitenon cells in the surface layer. The results indicate that electrical currents of low amperage suppress adhesion-causing synovial proliferation in the epitenon and promote active collagen synthesis in the tenocytes. This suggests the potential value of electrical stimulation in the control of adhesion formation after flexor tendon repair. PMID- 1640155 TI - Repair of the ruptured distal tendon of the biceps brachii. AB - The biceps brachii is the main supinator of the forearm. Unless the ruptured distal tendon is reattached to its correct anatomical site on the radial tuberosity, its action cannot be restored. We report four cases treated surgically, who all regained full forearm function, and on the basis of our experience suggest a simple method of reattaching the tendon. PMID- 1640157 TI - School reform: opportunities for excellence and equity for individuals with learning disabilities. A special report by the National Joint Committee on Learning Disabilities. PMID- 1640156 TI - Irlen lenses. PMID- 1640158 TI - Reading disabilities and aggression: a critical review. AB - Several authors have suggested that there is a strong association between specific learning disabilities and aggression, antisocial behavior, and juvenile delinquency. Claims that learning disabilities cause aggressive behavior and delinquency are increasingly common in the popular press, and a variety of theories concerning this purported causal relationship have been proposed. This research is flawed by a lack of specificity in the definition of learning disabilities, with studies often examining heterogeneous groups of children with learning problems. The present review examines the relationship between specific reading disabilities (the most frequently diagnosed learning disability) and aggressive behavior. The data suggest that there is not enough evidence to conclude that reading disability causes aggressive or delinquent behavior, although limited evidence does suggest that reading disability may worsen preexisting aggressive behavior. PMID- 1640159 TI - Cluster analysis of children and adolescents with brain damage and learning disabilities using neuropsychological, psychoeducational, and sociobehavioral variables. AB - The purpose of the study was to employ psychoeducational, neuropsychological, and sociobehavioral (Conners Rating Scale) variables in determining if definable subtypes exist within a diverse population of subjects with learning disabilities (LD) and documented brain damage. The sample of 95 subjects (27% female and 73% male) had been referred for neuropsychological assessment at a large, Midwestern medical center. Mean age was 10.6 years. Brain damage (BD) was documented for 45% of the sample. The first cluster analysis employed neuropsychological, psychoeducational, and sociobehavioral data and revealed four interpretable clusters. A second cluster analysis excluded sociobehavioral data and yielded two interpretable clusters. In neither analysis did a cluster consist exclusively of BD or LD subjects. Results were interpreted as supporting the importance of the sociobehavioral component in LD subtyping, as well as supporting the contention that parallels may exist in cerebral function and/or structure between the LD and BD classifications. PMID- 1640160 TI - A reading level match study of nonword reading skills in poor readers with varying IQ. AB - This study evaluated the hypothesis that poor readers are characterized by poor nonword reading skills, but that a specific deficit, as opposed to a developmental lag, in nonword reading will be found only in subjects whose reading is discrepant from intellectual ability. To test this hypothesis, we measured nonword reading skills in 93 (64 male, 29 female) third-grade poor readers and 54 (37 male, 17 female) fifth-grade poor readers (with and without reading/IQ discrepancies) who were matched to 147 (81 male, 66 female) nondisabled first graders on word identification skills. Results showed third- and fifth-grade poor readers to be significantly more impaired than word identification level match first graders on all measures on nonword reading. These findings were not related to the verbal IQ level within the poor reader groups and, thus, provide strong evidence for a deficit in nonword reading skills that is not explained by verbal intelligence. PMID- 1640161 TI - The effects of computer-based attribution retraining on the attributions, persistence, and mathematics computation of students with learning disabilities. AB - The purpose of the present study was to examine the impact of attribution retraining, embedded within a mathematics computer-assisted instructional (CAI) program, on students' attributions, persistence, and mathematics computation. Twenty-nine school-identified students with learning disabilities from five urban schools participated in the study. The sample's mean age was 13.3 years. After blocking on initial attributional patterns, students were randomly assigned to a mathematics CAI program that provided either attribution retraining or neutral feedback. Students used their assigned program for eight 30-minute sessions. Results did not support the contention that attribution retraining would have a significant impact on students' attributions. However, students who participated in the attribution retraining condition completed significantly more levels of the program than their counterparts who received neutral feedback. Attribution retraining students also obtained significantly higher scores on a test of problems practiced during the CAI program. These results suggest that attribution retraining may be a desirable addition to the type of feedback typically provided by CAI programs. However, they also highlight the need for further research that examines the conditions under which specific attributions are most advantageous. PMID- 1640162 TI - Drug addiction and mother/child welfare. Rights, laws, and discretionary decisionmaking. PMID- 1640163 TI - The adequacy of hospital reimbursement under Medicaid's Boren Amendment. PMID- 1640164 TI - Cytokine secretion by immune cells in space. AB - Cultured, bone marrow-derived macrophages, murine spleen and lymph node cells, and human lymphocytes were tested for their ability to secrete cytokines in space. Lipopolysaccharide-activated bone marrow macrophages were found to secrete significantly more interleukin-1 and tumor necrosis factor when stimulated in space than when stimulated on earth. Murine spleen cells stimulated with poly I:C in space released significantly more interferon-alpha at 1 and 14 hours after stimulation than cells stimulated on earth. Similarly, murine lymph node T cells and human peripheral blood lymphocytes, stimulated with concanavalin A in space, secreted significantly more interferon-gamma than ground controls. These data suggest that space flight has a significant enhancing effect on immune cell release of cytokines in vitro. PMID- 1640166 TI - The role of oxidative stress in disease progression in individuals infected by the human immunodeficiency virus. AB - This review describes the potential role of oxidative stress as a cofactor of disease progression from asymptomatic human immunodeficiency virus (HIV) infection to the acquired immunodeficiency syndrome (AIDS). Oxidative stress is a known activator of HIV replication in vitro through the activation of a factor that binds to a DNA-binding protein, NF-kappa B, which in turn stimulates HIV gene expression by acting on the promoter region of the viral long terminal repeat. Tumor necrosis factor alpha (TNF-alpha), an essential cytokine produced by activated macrophages, is also involved in the activation of HIV infection through similar mechanisms. TNF-mediated cytotoxicity of cells exposed to this substance is related to the generation of intracellular hydroxyl radicals. An indirect argument in favor of the role of oxidative stress in HIV-associated disease progression is the consumption of glutathione (GSH), a major intracellular antioxidant, during HIV infection and progression. GSH is known to play a major role in regulation of T cell immune functions. Oxidative stress may also play an important role in the genesis of cellular DNA damage and, in this context, may be related to HIV-associated malignancies and disease progression. Finally, the role of antioxidants as components of therapeutic strategies to combat HIV disease progression is discussed. PMID- 1640165 TI - Subcellular localization of CD66, CD67, and NCA in human neutrophils. AB - CD66 and CD67 are granulocyte-specific activation antigens; their surface expression is up-regulated when neutrophils are activated. CD66 antibodies recognize an approximately 180-kd neutrophil surface protein that is also recognized by anti-carcinoembryonic antigen (CEA) antibodies and is therefore a nonspecific cross-reacting antigen (NCA). CD67 antibodies recognize an approximately 100-kd neutrophil surface protein that is attached to the membrane via a glycosyl-phosphatidylinositol anchor. To identify an intracellular pool from which CD66 and CD67 could be up-regulated, the subcellular distribution of proteins recognized by CD66 and CD67 monoclonal antibodies and polyclonal anti CEA was studied. Neutrophil plasma membranes, granules, and cytoplasm were prepared by nitrogen cavitation and differential centrifugation and then analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Most of the 180-kd protein recognized by CD66 antibodies and the 100-kd protein recognized by CD67 antibodies were located in the secondary granule fraction, with lesser amounts detectable in the plasma membrane fraction. Several NCA species ranging from approximately 40 to 200 kd were identified, and the distribution of these NCAs was different in the primary granules, secondary granules, and plasma membrane fractions. The major NCAs in the plasma membrane fraction were of approximately 95 to 100 and approximately 180 to 200 kd; the secondary granule fraction contained major NCAs of approximately 42, 85, 95 to 100, and 180 to 200 kd. NCAs were also detected in the primary granule fraction, the most prominent being of approximately 90-100 kd; no NCA of approximately 180 to 200 kd was detected in the primary granules. The presence of CD66, CD67, and NCAs in the secondary granules suggests secondary granules as a likely source from which these antigens could be recruited to the cell surface with activation. The potential role for NCAs in the primary granules is unknown. PMID- 1640167 TI - Regulatory role of cytokines in IgE-mediated allergy. AB - The discovery of immunoglobulin E (IgE) is considered the most important contribution, to date, in the field of clinical allergy. Studies in rodents and humans have suggested that IgE production could be regulated by antigen-specific helper and suppressor T cells and by isotype-specific factors having affinity for IgE. In recent years, the synthesis of IgE has been shown to be regulated, in part, by a cytokine network. This review summarizes the cytokines that up regulate (interleukins-4, 5, and 6) and down-regulate (interferon-gamma and interleukin-2) the production of IgE. Emphasis is placed on IL-4 and IFN-gamma, two lymphokines known to play a major, but reciprocal, role in IgE synthesis. Increased insight into the various mechanisms of IgE control by cytokines and their receptors will eventually lead to improved treatment strategies in the clinical management of IgE-mediated allergy. PMID- 1640168 TI - Inhibitory role of interleukin-6 in macrophage proliferation. AB - We have shown that there are two forms of progenitor cells for macrophages. The first is characterized by a short lag period (about 1 day) before initiating the cell cycle, forms large colonies, is found in the bone marrow, and is in the nonadherent fraction. The second progenitor cell, found primarily in the adherent cell fraction of bone marrow and in peripheral tissues, forms small colonies after 14 days. We investigated the effect of combining interleukin-6 (IL-6) with colony-stimulating factor 1 (CSF-I) on macrophage proliferation. We found that IL 6 inhibited the proliferation of both types of progenitor cells, as well as more differentiated macrophages. This inhibitory effect was reversible because macrophages could initiate a proliferative response after removal of IL-6 from the culture medium. The introduction of anti-IL-6 into macrophage cultures containing IL-6 allowed proliferation, indicating that the effect was IL-6 specific. These results suggest that IL-6 may play a regulatory role in vivo by suppressing the production of bone marrow and tissue macrophages. PMID- 1640169 TI - Mouse macrophages contain a truncated CD4 transcript. AB - Mouse macrophages do not express CD4 on their surfaces. We used the polymerase chain reaction to investigate CD4 gene transcription in individual clones of primary mouse splenic macrophages and cell lines of spleen and bone marrow macrophages. The results show only the presence of CD4 mRNA transcripts that are truncated in the 3' coding sequence, thus explaining the lack of expression of a mature CD4 gene product by these cells. PMID- 1640170 TI - Monoclonal antibody NIMP-R10 directed against the CD11b chain of the type 3 complement receptor can substitute for monoclonal antibody 5C6 to exacerbate listeriosis by preventing the focusing of myelomonocytic cells at infectious foci in the liver. AB - Treatment of mice with a monoclonal antibody (mAb) designated NIMP-R10, directed against the CD11b polypeptide of the CD18/CD11b heterodimeric type 3 complement receptor (CR3), exacerbates listeriosis by preventing myelomonocytic cells from focusing at sites of infected hepatocytes in the liver. Under these conditions an otherwise sublethal Listeria inoculum grows unrestrictedly within hepatocytes and causes death in 3 days. The results obtained with NIMP-R10 are similar to those previously obtained with a different anti-CD11b mAb (5C6), although mAb NIMP-R10 is more effective at enhancing infection. Therefore, both mAbs can be used to analyze host antibacterial defenses in vivo. PMID- 1640171 TI - Increased CD4/CD8 coexpressed cells in a healthy subject. PMID- 1640172 TI - Tissue-specific expression of murine IP-10 mRNA following systemic treatment with interferon gamma. AB - We have examined the tissue distribution of 10-kd inflammatory protein (IP-10) mRNA expression in C57Bl/6 mice injected intravenously (i.v.) with various inflammatory stimuli. IP-10 mRNA was strongly induced by interferon-gamma (IFN gamma) in liver and kidney but only poorly in skin, heart, and lung. IFN-gamma had nearly equivalent access to these tissues as indicated by the distribution of radiolabeled recombinant IFN-gamma 1 h after injection. The time course of IP-10 mRNA appearance was rapid and transient in both liver and kidney; maximal expression in the liver (2 h) preceded that in the kidney (3 h) and declined rapidly thereafter in both tissues. Expression of IP-10 mRNA in the liver and kidney was highly sensitive to IFN-gamma treatment; nearly maximal stimulation occurred with injection of 500 U of IFN-gamma per mouse. Comparable stimulation of IP-10 mRNA expression in splenic macrophages required 10,000 U of IFN-gamma administered i.v., indicating that liver and kidney responses are 10- to 20-fold more sensitive. IP-10 mRNA expression in both tissues was not restricted to stimulation by IFN-gamma but was also seen with injection of lipopolysaccharide (LPS) (25 micrograms/mouse) or IFN-beta (100,000 U/mouse). Two other members of the IP-10 gene family, KC (gro) and JE (MCP-1), were expressed at lower levels under similar treatment conditions. Analysis of IP-10 mRNA distribution in the liver and kidney by in situ hybridization indicated that expression in both tissues was most prominent in the reticuloendothelial cell system, particularly in the endothelial lining of the microvascular circulation. Although the function of the IP-10 gene product has not been defined, these results suggest that it may play an important role in the response of both the liver and kidney to systemic inflammation. PMID- 1640173 TI - Wheat germ agglutinin inhibits the C5a receptor interaction: implications for receptor microheterogeneity and ligand binding site. AB - Wheat germ agglutinin (WGA) has been shown to inhibit the interaction of C5a with the C5a receptor on both polymorphonuclear neutrophils (PMNs) and the histiocytic cell line U937. The level of inhibition with isolated receptor preparations is 100%, and on intact cells 10 to 20% of the receptor population appear to retain their ability to bind C5a in the presence of WGA. In contrast, this lectin completely inhibits the C5a-mediated degranulation of PMN primary and secondary granules, suggesting that the population of C5a receptors responsible for mediating degranulation is also recognized by WGA. More than 50% of the receptors appear to be blocked before an effect on degranulation occurs. This inhibition by WGA does not appear to be due to down-regulation of C5a receptors from the cell surface, excessive aggregation of receptor sites, or interaction of WGA with the carbohydrate portion of the C5a molecule. The inhibition is reversed by N acetylglucosamine but not by sialic acid. This effect appears to be specific for WGA because various other lectins do not inhibit the C5a receptor interaction. That the inhibition by WGA is due to direct binding of the lectin to N acetylglucosamine residues on the C5a receptor is strongly supported by the ability of the cross-linked C5a-receptor complex to bind to and be specifically eluted from a WGA-Affigel affinity matrix. These observations are consistent with hypothesis that the population of C5a receptors on leukocytes exhibits microheterogeneity with respect to structure (carbohydrate content) and/or function. PMID- 1640174 TI - Interleukin-8 induces changes in human neutrophil actin conformation and distribution: relationship to inhibition of adhesion to cytokine-activated endothelium. AB - Interleukin-8 (IL-8) induces diverse biological responses in neutrophils, including inhibition of adhesion to cytokine-activated endothelium, which we have termed the leukocyte adhesion inhibition (LAI) effect. Pretreatment of neutrophils with cytochalasin B abolished the LAI effect of IL-8, suggesting a microfilament-dependent mechanism. Interleukin-8 induced a rapid increase (less than or equal to 15 s) in the polymerization of actin filaments in human neutrophils that was blocked by pretreatment with cytochalasin B. F-actin depolymerization occurred gradually at a rate inversely proportional to IL-8 concentration. This temporal pattern of actin polymerization-depolymerization was similar to that induced by other chemotactic factors such as C5a and N formylmethionyl-leucyl-phenylalanine, which also exhibit a marked LAI effect, but the lipid mediators, leukotriene B4 and platelet-activating factor, lack any significant LAI effect. Scanning confocal microscopy demonstrated that neutrophil actin microfilaments undergo a dramatic rearrangement prior to detachment of the neutrophil from a surface. We suggest that the ability of IL-8 and certain other leukocyte agonists to regulate the actin polymer network of neutrophils may play an important role in adhesive interactions with the vascular endothelium. PMID- 1640176 TI - Interactions between HIV-infected monocytes and the extracellular matrix: increased capacity of HIV-infected monocytes to adhere to and spread on extracellular matrix associated with changes in extent of virus replication and cytopathic effects in infected cells. AB - Monocytes express cell surface receptors for extracellular matrix (ECM) proteins of basement membranes. These receptors are engaged during extravasation of cells through capillary endothelium into tissue. The number of human immunodeficiency virus (HIV)-infected monocytes that adhered to ECM over 2 h was threefold higher than that of uninfected control cells. This difference was ECM specific and was not observed with a bovine serum albumin substrate. Enhanced adhesion to ECM was evident in monocytes by 4 days after HIV infection and increased through 10 days. Monocytes exposed to a T cell-tropic HIV strain that binds to but does not replicate in monocytes showed no changes in adherence to ECM. Thus, productive infection of monocytes by HIV induces a significant increase in the capacity of these cells to interact with ECM. Enhanced adhesion of HIV-infected monocytes to ECM was associated with increased spreading: at 12 h, sixfold more HIV-infected monocytes were spread on ECM than were uninfected control cells. Cell processes of HIV-infected monocytes formed a complex network on ECM: many of these cells expressed HIV proteins as detected by indirect immunofluorescence. HIV-associated cytopathic effects and levels of virion-associated reverse transcriptase activity depended on the substrate to which monocytes were attached. Virus replication and cytopathic effects in monocytes adhered to ECM, fibronectin, or plastic alone were comparable. In contrast, HIV-infected monocytes attached to laminin showed a significant increase in virus replication and in extent of cytopathic effects through 2 weeks after infection. The lowest levels of HIV replication and cytopathic effects were in monocytes attached to collagen IV. Interactions between monocytes and ECM profoundly affect the manner in which these cells control HIV infection: HIV infection changes the capacity of infected monocytes to attach and spread on ECM; attachment to ECM alters the extent of virus replication in infected cells. PMID- 1640175 TI - Development, differentiation, and proliferation of epidermal Langerhans cells in rat ontogeny studied by a novel monoclonal antibody against epidermal Langerhans cells, RED-1. AB - An antirat monoclonal antibody (mAb) against nonlymphoid dendritic cells, RED-1, was produced using epidermal Langerhans cells (LCs) as the immunogen. This mAb reacted mainly with the LCs and indeterminate dendritic cells (ICs), interdigitating cells in the T cell areas of lymphoid tissues, and monocyte/macrophages in various organs and tissues of adult rats. In the epidermal sheets prepared from adult rats, it specifically recognized the cell surface antigen(s) present on LCs and ICs. In the fetal rat skin, primitive or fetal macrophages migrated into the epidermis and expressed RED-1 at fetal day 17. With advance of gestation, RED-1-positive cells increased, started expressing Ia antigens at fetal day 18, and subsequently differentiated into dendritic cells. Most of them showed Ia expression by fetal day 20 and differentiated into LCs within a few days after birth. The labeling index of 5-bromo-2'-deoxyuridine in RED-1-positive cells was 18% at fetal day 17 and decreased to 5 to 6% in the postnatal period. These results imply that proliferative capacity of RED-1 positive cells is important for the formation and expansion of the IC population in the fetal stage and for the survival of LCs in the postnatal period. PMID- 1640177 TI - Listericidal and nonlistericidal mouse macrophages differ in complement receptor type 3-mediated phagocytosis of L. monocytogenes and in preventing escape of the bacteria into the cytoplasm. AB - Listeria monocytogenes is a facultative intracellular bacterium that escapes phagocytic vesicles and replicates in the cytoplasm, where it becomes coated with F-actin. Macrophages, important anti-Listeria effector cells, are heterogeneous in their ability to kill Listeria. Complement receptor type 3 (CR3) mediates most phagocytosis of Listeria by listericidal macrophages. Experiments described here tested whether nonlistericidal macrophages also phagocytosed Listeria through CR3 and whether the ability of Listeria to escape into the cytoplasm correlated with lack of listericidal activity. We show here that CR3 mediated an average of 66% of the phagocytosis of serum-opsonized Listeria by listericidal peptone-elicited macrophages but only 35% by nonlistericidal thioglycolate-elicited macrophages. In thioglycolate-elicited macrophages, most Listeria were cytoplasmic and actin coated, whereas in peptone-elicited macrophages most were retained in the phagosome. These results indicate that listericidal and nonlistericidal macrophages phagocytose Listeria through different receptors and that nonlistericidal macrophages allow Listeria to escape into the cytoplasm. PMID- 1640178 TI - Asymptotic rates of growth of the extinction probability of a mutant gene. AB - We prove that a result of Haldane (1927) that relates the asymptotic behaviour of the extinction probability of a slightly supercritical Poisson branching process to the mean number of offspring is true for a general Bienayme-Galton-Watson branching process, provided that the second derivatives of the probability generating functions converge uniformly to a non-zero limit. We show also by examples that such a result is true more widely than our proof suggests and exhibit some counter-examples. PMID- 1640179 TI - The survival probability of a mutant in a multidimensional population. AB - We prove a general result about the asymptomatic behaviour of the survival probability of a slightly supercritical multitype Bienayme-Galton-Watson branching process. This is the complete analogue of a result which Ewens (1968) obtained for a Poisson branching process. PMID- 1640180 TI - Rates of decay for the survival probability of a mutant gene. AB - If qk is the extinction probability of a slightly supercritical branching process with offspring distribution [pkr:r = 0, 1, 2, ...], then it is shown that if supk sigma r r3pkr less than infinity, inf sigma 2k greater than 0, and mk----1, then 1-qk approximately 2(mk - 1)sigma -2k, where mk = sigma r rpkr, sigma 2k = k sigma r r2pkr - m2k. This provides a simple set of sufficient conditions for the validity of a conjecture of Ewens (1969) for the survival probability of a slightly advantageous mutant gene. PMID- 1640181 TI - Survival probabilities for some multitype branching processes in genetics. AB - Consider a positively regular, slightly supercritical branching process with K types. An approximation to the probability of survival of a line descended from a single individual of type i has recently been derived by Hoppe. If K is large, however, this approximation may not be easy to compute. A further approximation that is easily computable is given. The result is used to estimate probabilities of survival of an allele A that is originally present in one male or one female in a large, random mating, age-structured population. Both autosomal and sex linked loci are considered. Another application of the approximation is also discussed. PMID- 1640182 TI - Mutation in autocatalytic reaction networks. An analysis based on perturbation theory. AB - A class of kinetic equations describing catalysed and template induced replication, and mutation is introduced. This ODE in its most general form is split into two vector fields, a replication and a mutation field. The mutation field is considered as a perturbation of the replicator equation. The perturbation expansion is a Taylor series in a mutation parameter lambda. First, second and higher order contributions are computed by means of the conventional Rayleigh-Schrodinger approach. Qualitative shift in the positions of rest points and limit cycles on the boundary of the physically meaningful part of concentration space are predicted from flow topologies. The results of the topological analysis are summarized in two theorems which turned out to be useful in applications: the rest point migration theorem (RPM) and the limit cycle migration theorem (LCM). Quantitative expressions for the shifts of rest points are computed directly from the perturbation expansion. The concept is applied to a collection of selected examples from biophysical chemistry and biology. PMID- 1640183 TI - How the anisotropy of the intracellular and extracellular conductivities influences stimulation of cardiac muscle. AB - The bidomain model, which describes the behavior of many electrically active tissues, is equivalent to a multi-dimensional cable model and can be represented by a network of resistors and capacitors. For a two-dimensional sheet of tissue, the intracellular and extracellular conductivity tensors can be visualized as two ellipses. For any pair of conductivity tensors, a coordinate transformation can be found that reduces the extracellular ellipse to a circle and aligns the intracellular ellipse with the coordinate axes. The eccentricity of the intracellular ellipse in this new coordinate system is an important parameter. It can have two special values: zero (in which case the tissue has equal anisotropy ratios) or one (in which case the tissue is comprised of one-dimensional fibers coupled through the two-dimensional extracellular space). Thus the bidomain model provides a unifying framework within which the electrical behavior of a wide variety of nerve and muscle tissues can be studied. When the anisotropy ratios in the intracellular and extracellular domains are not equal, stimulation with an anode always causes depolarization of some region of tissue. An analogous effect occurs in models that describe one-dimensional fibers, in which an "activating function" determines the site of stimulation. Experiments indicate that cardiac muscle does not have equal anisotropy ratios. Therefore, models developed to describe stimulation of axons may also help in understanding stimulation of two- or three-dimensional cardiac tissue, and may explain the concept of anodal stimulation of cardiac tissue through a "virtual cathode". PMID- 1640184 TI - A threshold result for an epidemiological model. AB - A threshold parameter R0 is identified for an SIRS epidemiological model which has nonlinear incidence and a distributed delay for transfer out of the removed class. For R0 less than 1, the disease free equilibrium is proved to be the global attractor for all solutions. PMID- 1640185 TI - Sodium-extruding and calcium-extruding sodium/calcium exchangers display similar calcium affinities. AB - Na+/Ca2+ exchange activities in purely inside-out and mixed inside-out and right side-out fish enterocyte basolateral plasma membrane vesicle preparations display equal affinities for Ca2+, showing that only the intracellular Ca2+ transport site of the Na+/Ca2+ exchanger is detected in experiments on vesicle preparations with mixed orientation. Therefore, Ca2+ pump and Na+/Ca2+ exchange activity may be compared directly without correction for vesicle orientation. The Na+/Ca2+ exchange activity in fish enterocyte vesicles is compared to the activity found in dog erythrocyte vesicles. The calcium-extruding exchanger in fish basolateral plasma membranes shows values of Km and V(max) for calcium similar to those found for the sodium-extruding exchanger in dog erythrocyte membranes, indicating that differences in electrochemical gradients underlie the difference in cellular function of the two exchangers. PMID- 1640186 TI - Scaling of muscle fibres and locomotion. AB - To reconcile the scaling of the mechanics and energetics of locomotion to recent data on the scaling of the mechanics of muscle fibres, I have extended the theory of Taylor and colleagues that the energetic cost of locomotion is determined by the cost of generating force by the fibres. By assuming (1) that the cost of generating force in a fibre is proportional to V(max) (maximum velocity of shortening) and (2) that, at physiologically equivalent speeds, animals of different body sizes recruit the same fibre types, this extension quantitatively predicts the scaling of the energetics of locomotion, as well as other observations, from the scaling of V(max) of the muscle fibres. First, the energetic cost of locomotion at physiologically equivalent speeds scales with Mb 0.16, where Mb is body mass, as does V(max) of a given fibre type. However, the energetic cost at absolute speeds (cost of transport) scales with Mb-0.30, because small animals must compress their recruitment order into a narrower speed range and, hence, recruit faster muscle fibre types at a given running speed. Thus, it costs more for small animals to move 1 kg of their body mass 1 km not only because a given muscle fibre type from a small animal costs more to generate force than from a large one, but also because small animals recruit faster fibre types at a given absolute running speed. In addition, this analysis provides evidence that V(max) scales similarly to 1/tc (where tc is foot contact time) and muscle shortening velocity (V), in agreement with recent models. Finally, this extension predicts that, at physiologically equivalent speeds, the weight specific energetic cost per step is independent of body size, as has been found empirically. PMID- 1640187 TI - Biochemical comparison of fast- and slow-contracting squid muscle. AB - The myofilament protein compositions of muscle fibres from the transverse muscle mass of the tentacles and the transverse muscle mass of the arms of the loliginid squid Sepioteuthis lessoniana were compared. These two muscle masses are distinct types, differing in their ultrastructural and behavioural properties. The transverse muscle of the tentacles consists of specialized muscle fibres that exhibit cross-striation and unusually short sarcomeres and thick filaments. The transverse muscle of the arms consists of obliquely striated muscle fibres that are typical of cephalopod skeletal muscle in general. The specialization of the tentacle muscle results in a high shortening speed and reflects its role in creating rapid elongation of the tentacles during prey capture. Comparison of samples of myofilament preparations of the two muscle fibre types using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and peptide mapping of myosin heavy chains from the two muscle fibre types, however, showed little evidence of differences in contractile protein isoforms. Thus, specialization for high shortening speed appears to have occurred primarily through changes in the dimensions and arrangement of the myofilament lattice, rather than through changes in biochemistry. The thick filament core protein paramyosin was tentatively identified in the squid muscle fibres. This protein was less abundant in the short thick filament cross-striated tentacle muscle cells than in the obliquely striated arm cells. PMID- 1640188 TI - Prophylaxis: the next haemophilia treatment. PMID- 1640189 TI - A Swedish view on the diagnosis of renovascular hypertension. PMID- 1640190 TI - Twenty-five years' experience of prophylactic treatment in severe haemophilia A and B. AB - In Sweden, prophylactic treatment of boys with severe haemophilia has been practised since 1958 in an attempt to convert the disease from a severe to a milder form. The present study population consisted of 60 severe haemophiliacs (52 A, 8 B), aged 3-32 years. Treatment is started when the boys are 1-2 years of age, the regimens used being 24-40 IU F VIII kg-1 three times weekly in haemophilia-A cases (i.e. greater than 2000 IU kg-1 annually) and 25-40 IU F IX kg-1 twice weekly in haemophilia-B cases. The orthopaedic and radiological joint scores (maximum scores of 90 and 78, respectively) are evaluated as recommended by the World Federation of Haemophilia. Of those subjects aged 3-17 years, 29 out of 35 individuals had joint scores of zero. The oldest group had only minor joint defects. The VIII:C and IX:C concentrations had usually not fallen below 1% of normal. All 60 patients are able to lead normal lives. In conclusion, it appears to be possible to prevent haemophilic arthropathy by giving effective continuous prophylaxis from an early age, and preventing the VIII:C or IX:C concentration from falling below 1% of normal. PMID- 1640191 TI - Close correlation between high-density lipoprotein and triglycerides in normotriglyceridaemia. AB - The relationship between high-density-lipoprotein (HDL) particle size subclasses and the levels of the major lipoprotein lipids was studied in 74 men consecutively referred to the lipid clinic. HDL (density 1.070-1.21 kg l-1) was separated by polyacrylamide gradient gel electrophoresis (GGE) into five size defined subclasses, in order of decreasing size as follows: HDL2b, HDL2a, HDL3a, HDL3b and HDL3c. Cholesterol and triglyceride concentrations in very-low-density (VLDL), low-density (LDL) and high-density (HDL) lipoproteins were determined. The level of VLDL triglycerides was negatively correlated with HDL2b (r = -0.66, P less than 0.0001), and positively correlated with HDL3b concentrations (r = 0.65, P less than 0.0001). Both correlations were restricted to subjects with VLDL triglyceride concentrations of less than 1.80 mmol l-1, i.e. those with normotriglyceridaemia. Patients with a history of myocardial infarction and/or angina pectoris (n = 18) had significantly lower HDL2b levels than subjects with asymptomatic hyperlipidaemia (n = 50), i.e. 0.16 vs. 0.22 mg protein ml-1 (P less than 0.05), despite essentially similar cholesterol and triglyceride levels in the VLDL, LDL and HDL fractions, including HDL2 and HDL3 cholesterol. PMID- 1640192 TI - Improved working capacity in patients with ischaemic heart disease during a 10 day treatment with oral theophylline. AB - The objective of this study was to assess whether a 10-d treatment with oral theophylline improves the working capacity in patients with ischaemic heart disease, and to compare theophylline with conventional anti-anginal therapy. Twenty-four patients with stable effort-induced angina were included in the study. The patients received double-blind treatment in randomized order during 4 consecutive 10-d periods, separated by a 4-d wash-out period, with (a) metoprolol durules 200 mg once daily + theophylline durules 300 mg b.i.d., (b) theophylline + placebo, (c) metoprolol + placebo, and (d) placebo alone. At the end of each period a supine exercise stress test was performed. Maximal workload increased to 111 +/- 6 W during treatment with theophylline, compared to 106 +/- 6 W during placebo treatment (P = 0.01). Metoprolol increased the maximal workload to 117 +/ 6 W (P less than 0.001). The effects of metoprolol and theophylline were additive, and the working capacity increased to 123 +/- 7 W during combined therapy. Neither the degree of ST-depression nor the scoring of chest pain at maximal workload differed between the four treatment regimens. An improved working capacity was shown in patients with stable effort-induced angina pectoris during long-term theophylline treatment. The effect was additive to that of beta blockade. PMID- 1640193 TI - Low plasma levels of insulin-like growth factor 1 (IGF-1) in male patients with idiopathic osteoporosis. AB - Experimental studies in vitro indicate that insulin-like growth factor 1 (IGF-1) could be of importance for normal bone growth and remodelling, but the clinical relevance of these observations is unknown. In 12 consecutive young to middle aged male patients (mean age (+/- SD) 46 +/- 8 years, range 30-57 years) with symptomatic idiopathic osteoporosis, the plasma concentrations of IGF-1 were significantly lower than in healthy subjects (0.51 +/- 0.25 vs. 0.73 +/- 0.23 U ml-1; P less than 0.01). The bone mineral densities in the spine, the femoral neck, and the forearm were significantly different between patients and control subjects. There were positive correlations between the plasma IGF-1 concentrations and the bone densities of the spine and the forearm. Three of the patients received a 5-d course of human recombinant growth hormone (GH). During this short period significant increases in plasma IGF-1 levels and in biochemical indices of bone turnover (serum bone-specific alkaline phosphatase, urinary calcium excretion) were recorded. These observations indicate that circulating IGF-1 could have an important role in maintaining bone mass, and suggest that impairment of IGF-1 production is involved in the pathogenesis of osteoporosis. PMID- 1640195 TI - Function of terminal ileum in patients with Yersinia-triggered reactive arthritis. AB - In order to study the function of the intestinal epithelium in the terminal ileum, the Schilling test was performed in 10 patients with Yersinia-triggered reactive arthritis, in 10 patients who had recovered from Yersinia enteritis without complications, and in five patients with rheumatoid arthritis treated with non-steroidal anti-inflammatory agents. The Schilling test indicates absorption of vitamin B12 in the terminal ileum, i.e. the area affected by Yersinia and inflamed in patients with reactive arthritis. The findings obtained demonstrate increased uptake through the epithelium in this area of the intestine in patients with Yersinia-triggered reactive arthritis. There are two possible explanations. First, Yersinia infection may have a long-term effect on the gut mucosa. Secondly, some individuals may, at the level of the terminal ileum, show enhanced absorption of vitamin B12 and/or other substances such as microbes or their components, resulting in increased susceptibility to certain infections. PMID- 1640194 TI - Autonomic nervous function and its relationship to cardiac performance in middle aged diabetic patients without clinically evident cardiovascular disease. AB - Autonomic nervous function was evaluated in 36 patients with insulin-dependent diabetes mellitus (IDDM), 39 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 48 control subjects, all without clinically evident cardiovascular disease. Valsalva ratio and heart rate variation during deep breathing were lower in both diabetic groups than in the control group. Autonomic nervous function score (ANFS) was more abnormal in patients with IDDM than in control subjects, but was not significantly increased in patients with NIDDM. There was a negative correlation between ANFS and left ventricular diastolic filling evaluated by echocardiography or peak heart rate during exercise in both diabetic groups. There were no correlations between ANFS and left ventricular systolic function at rest or during exercise in any of the groups. In conclusion, autonomic nervous function was abnormal in middle-aged diabetic patients, and it was associated with impaired left ventricular diastolic filling at rest and decreased heart rate response to exercise, but not with left ventricular systolic function. PMID- 1640196 TI - Bilateral emphysematous pyelonephritis resolving to medical therapy. AB - We describe a case of bilateral emphysematous pyelonephritis, in a diabetic female, that responded to medical therapy alone. Her complete improvement is documented radiologically. Emphysematous pyelonephritis, as a cause of serious infection in diabetic patients, is briefly reviewed. PMID- 1640197 TI - Inhibition of Ca2+ uptake in freshwater carp, Cyprinus carpio, during short-term exposure to aluminum. AB - In carp exposed to pH 5.2 in fresh water, the Ca2+ influx from the water is reduced by 31% when compared to fish in water of neutral pH. At pH 5.2, the Ca2+ influx but not Na+ uptake is decreased by aluminum (Al). Al reduces Ca2+ influx dose-dependently: a maximum 55% reduction was observed after 1-2 h exposure to 200 micrograms.1(-1) (7.4 microM) Al. Branchial Ca2+ efflux is less sensitive to Al and affected only by exposure for more than 1 h to high Al concentrations. Na+ influx is not affected by concentrations Al up to 400 micrograms.1(-1). Na+ efflux, similarly to Ca2+ efflux, increased when fish were exposed for more than 1 h to 400 micrograms.1(-1) Al. PMID- 1640198 TI - Calcitonin-like immunoreactivity in the blue crab: tissue distribution, variations in the molt cycle, and partial characterization. AB - Calcitonin-like immunoreactivity has been found in blood and tissues of the marine blue crab, Callinectes sapidus Rathbun. The activity in blood rises significantly during the immediate premolt (D4) stage, but tissue immunoreactivity does not vary significantly with molt stage. The immunoreactivity to antisalmon calcitonin serum is due to a 27.2 kDa protein that shows strong similarities in amino acid composition to a similar protein in a lobster and to human calcitonin precursor. The protein is most abundant in the midgut glands (hepatopancreas), but is also found in significant quantities in several other tissues. Immunoreactivity in the blood appears to be primarily due to the same molecular weight fraction, with secondary contributions from smaller molecules, closer in size to vertebrate calcitonin. A physiological function of the calcitonin-like substance in calcium transport during or after molt has yet to be demonstrated. PMID- 1640199 TI - Effects of human insulin-like growth factor-I on release of growth hormone by rainbow trout (Oncorhynchus mykiss) pituitary cells. AB - A recombinant human IGF-I (rhIGF-I) was applied to primary cultures of rainbow trout pituitary cells. In wells containing 3 x 10(4) and 6 x 10(4) cells/well, rhIGF-I inhibited basal GH release both in short (6 h) and long (12 and 24 h) exposures. The decline in GH release was dose-dependent over the range of 0.01 and 100 mM. The combination of rhIGF-I and low concentrations of synthetic somatostatin (SRIF) enhanced the inhibitory effect of rhIGF-I in an additive manner. Any appreciable effect of rhIGF-I on PRL release was not evidenced. To our knowledge, this report demonstrates for the first time the participation of IGFs on the inhibitory component of fish GH regulation. PMID- 1640200 TI - Development of the chick chorioallantoic capillary plexus under normoxic and normobaric hypoxic and hyperoxic conditions: a morphometric study. AB - Fertile eggs from the domestic fowl were incubated under normobaric normoxic (21% O2), hypoxic (14% O2), and hyperoxic (40% O2) conditions in order to examine the influence of the prevailing oxygen level on the growth and maturation of the chorioallantoic membrane. Eggs were sampled at regular stages throughout incubation for morphometric analysis. Under normoxic conditions, maturation of the capillary plexus occurred in two distinct stages, both of which contributed to a reduction in the thickness of the air-blood barrier. Between days 6 and 10, the capillaries sprouted and fused to form a dense plexus. Subsequently, between days 10 and 14, this plexus invaginated into the chorionic epithelium. Differentiation of the chorioallantoic membrane appeared maximal by the end of this period. Hypoxia resulted in diminished growth of the embryo and chorioallantoic membrane, but in accelerated maturation of the capillary plexus. Hyperoxia had a less marked effect but appeared to retard the final invagination of the plexus, resulting in a thicker air-blood barrier. PMID- 1640201 TI - Length regulation in the Dictyostelium discoideum slug is a late event. AB - Time-lapse video light microscopy was used to study the emergence and maturation of the migratory slug from a D. discoideum aggregate. The anterior part, the tip of this simple multicellular organism, establishes migration prior to the definition of the rear, and hence the length of the slug. It was found that newly formed slugs of wild-type strain WS380B can reach lengths greater than 1 cm, yet mature slugs of this strain are rarely longer than 2-3 mumm. Often the tip extended out of the aggregation mound upon an arching pillar of cells. After the tip first touched the substratum, it commenced migration with a rapid succession of movement steps. Here we show that at the initiation of migration, a differential rate of cell movement along the developing slug axis results in a series of complicated changes, before the stable and mature shape of the slug is formed. Our results lead to new conclusions about D. discoideum slug formation and shape maintenance. Evidence is presented for regulation of slug length. PMID- 1640202 TI - Activation of Xenopus laevis eggs in the absence of intracellular Ca activity by the protein phosphorylation inhibitor, 6-dimethylaminopurine (6-DMAP). AB - Xenopus laevis eggs pricked or microinjected with water or saline in medium containing a limited quantity of free Ca (1.0 to 2.0 microM) remain unactivated for at least 6 hr, even after transfer to oocyte medium containing Ca at higher concentrations (0.5-1.0 mM). These injected eggs, when later pricked in oocyte medium or exposed to A23187 or urethane are fully capable of activation. This confirms the observations of Wangh ('89). However, eggs injected in this Ca limited medium (CaLM) with 6-DMAP as well as those simply exposed to this drug undergo changes characteristic of activation, including cortical contraction, cortical granule breakdown, a loss of MPF and CSF activities, and pronuclear formation. The time required for 6-DMAP to induce egg activation is inversely correlated to its concentration. Interestingly, eggs that have been injected with EGTA, and thus are unable to respond to activation stimuli such as pricking and A23187 or urethane treatment, can also be activated by exposure to 6-DMAP. In contrast, eggs exposed to or injected with a 6-DMAP analogue (6-aminopurine or puromycin) or a protein synthesis inhibitor (cycloheximide or emetine or puromycin) are not activated. As well, eggs injected in CaLM with 6-DMAP simultaneously with a phosphatase inhibitor (NaF or ammonium molybdate) fail to become activated. Although 6-DMAP-activated eggs remain at the pronucleus stage so long as 6-DMAP is present, they resume cell cycle activities after the drug is withdrawn. They form cleavage furrows, disassemble pronuclear envelopes, and recondense chromosomes. Also, MPF activity reappears and cycles at least twice, peaking each time shortly before cleavage furrow formation. These results suggest that activation of Xenopus eggs arrested at metaphase II by inhibition of protein phosphorylation does not require intracellular Ca release and that maintenance of the egg at metaphase II depends upon continuous protein phosphorylation. PMID- 1640203 TI - Effect of slow and ultra-rapid freezing on cell surface antigens of 8-cell mouse embryos. AB - The distribution of four cell surface antigens (SSEA-1, SSEA-3, SSEA-4, and I) present on mouse preimplantation embryos was examined on 8-cell stage embryos immediately after flushing from the reproductive tract and after slow or ultra rapid freezing. Frozen-thawed and nonfrozen embryos were also examined after culture in vitro for 5, 24, or 48 h. Immediately after thawing, embryos showed a disruption in the polarity of cell surface antigens SSEA-3, SSEA-4, and I, but no differences were detected in fluorescence intensity or various other staining characteristics. No long-term changes in the distribution of cell surface components were detected. Implantation and embryonic development were similar for frozen and nonfrozen embryos transferred to the uterine horns of pseudopregnant recipients. PMID- 1640204 TI - Winners of the 1992 Teaching Awards. PMID- 1640205 TI - Vile thoughts on the new coding system. PMID- 1640206 TI - Nolo nocere. PMID- 1640207 TI - Neuropsychiatric effects of drugs in the elderly. AB - Since the elderly consume large numbers of drugs, drug-induced disease must be high on the list as a suspected cause of changes in behavior. Neuropsychiatric side effects of drugs in the elderly are not rare events. While proceeding to investigate medical, neurological, and psychiatric causes of a change in the cognitive status or behavior in an elderly patient, it is important to consider a possible psychotoxic drug as an offender or co-offender. Failing to do so may lead to inappropriate testing and further unnecessary and possibly deleterious therapeutic measures. In the case of dementia, the worst treatment would be institutionalization before identifying a drug as the cause of the cognitive dysfunction. PMID- 1640208 TI - Obesity. A big problem. Introduction. PMID- 1640209 TI - Role of dietary fat in obesity. Fat is fattening. AB - Total caloric intake has not increased significantly over the last century as obesity increased, but there has been an increase in consumption of dietary fat. Its role in obesity is reviewed. Fat is the most concentrated form of calories in the diet; being compact, it contributes to overeating. High fat foods can be eaten faster with less chewing. Dietary fat is the most efficiently stored foodstuff, thus contributing to obesity. A low fat diet is an important adjunct to advising decreasing caloric intake for a weight reduction plan. Physicians should advise patients to decrease fat, not just "count calories." PMID- 1640210 TI - Physician's and dietitian's role in obese care. AB - In the Surgeon General's Report on Nutrition and Health, of the ten leading causes of death in the United States, five are nutrition related. Instead of nutritional deficiencies as seen in the 1940s, the national diet has shifted to dietary excesses and imbalances. Dietary excesses and imbalances are reflected in obesity, a major health problem affecting approximately 30% of the United States' population. Unfortunately, the diet industry is not regulated and, hence, patients have many avenues from which to choose. Many of these leave patients lost and confused as to why they have failed in maintaining their weight loss. It is well documented that the recidivism rate in the obese is high with only 5% maintaining their weight loss after one year. The following is a review of the physician's and dietitian's roles in long-term weight maintenance. PMID- 1640211 TI - Community resources in obese care. AB - Community resources can augment care provided by physicians and dietitians for the obese. The well-distributed community resources in Florida are reviewed. They are well-established and provide emotional support, peer group dynamics, a variety of formats and prices, and information about food and life-style changes. PMID- 1640212 TI - Group office visits in obesity. AB - A conference convened by the NIH in 1985 officially designated obesity a health hazard, stopping short of calling it a disease; yet its characteristic progressive, debilitating and refractory nature is impressively disease-like. Long-term weight loss occurs in only 5% of patients. Group office visits led by physicians have been used in a number of life-style conditions. In diabetes this format enhances blood sugar control and in obesity it improves five-year weight loss success to 20%. In patients with coronary artery disease risk factor a 21% decrease in angina, 55% improvement of exercise tolerance, and 21% decrease in cholesterol occurred in a pilot study. Group office physician-led visits offer encouraging results for the mitigation of life-style conditions. PMID- 1640213 TI - Surgical approach to the obese patient. AB - Morbid obesity is a life-threatening disorder associated with medical and psychological complications. The failure of medical therapy has led to the development of a new surgical discipline called bariatric surgery, which has evolved over the past three decades. Initial techniques created malabsorption to produce weight loss. Due to complications, later techniques limited oral intake to produce weight loss. Currently, most bariatric surgeons perform either gastric bypass or gastric partition (vertical banded gastroplasty or vertical ring gastroplasty). However, other techniques are also being evaluated, including a modified intestinal bypass, gastric banding, and a new gastric balloon. Only with continued follow-up will we determine the ultimate risk/benefit ratio of these procedures and their place in the management of the morbidly obese. In the setting of an experienced multidisciplinary team committed to long-term follow up, surgical therapy can be considered. PMID- 1640214 TI - Exercise in the treatment of obesity. AB - Medical literature reveals that neither diet nor exercise are effective as single modes of intervention in the treatment of obesity. While it is logical that they be combined in the context of multidisciplinary treatment, restrictions in calorie or protein intakes while dieting may impair short-term or long-term function. While properly constituted diets can effectively preserve physical function across major weight loss, long-term preservation of this weight loss is strongly influenced by post-diet exercise habits. To develop these positive long term habits, patients need guidance on safe and effective exercise practices during dietary treatment of obesity, with the ultimate goal being life-long exercise behaviors that will contribute to sustained weight maintenance. PMID- 1640215 TI - Cytochrome P450. Mechanisms of action and clinical implications. AB - The term cytochrome P450 refers to a group of hemoproteins whose Fe(2+)-carbon monoxide complex shows an absorption spectrum with a maximum near 450 nm. There is a broad interest in the P450s because of their significance in a variety of disciplines ranging from medical genetics to inorganic chemistry. Cytochrome P450 enzymes are involved in the metabolism of drugs, carcinogens, steroids, pesticides, hydrocarbons and natural products. The toxicity of many of these products may be modulated, either via replacement or by the various oxidations catalyzed by the cytochrome P450 enzymes. In recent years the roles of cytochrome P450 enzymes in the metabolism of endogenous compounds have been partially elucidated. Physiological compounds such as steroids, fatty acids, prostanoids and other eicosanoids, fat-soluble vitamins and mammalian alkaloids have been shown to be substrates. Aside from their roles in metabolism, certain of these enzymes were found to be involved in the metabolic activation of a variety of chemical carcinogens and possibly in the overall process of chemical carcinogenesis. Studies show that alterations in cytochrome P450 activities toward various substrates have been implicated in diseases which affect human health. The roles are reviewed of the various cytochrome P450 enzymes in the metabolism of substrates which may be associated with clinical disease states. PMID- 1640216 TI - Risk management for individual practices. PMID- 1640217 TI - Concurrent care. PMID- 1640218 TI - Health care for the whole person. PMID- 1640219 TI - Contribution from all. PMID- 1640220 TI - Effects of conditioning depolarization and repetitive stimulation on Q beta and Q gamma charge components in frog cut twitch fibers. AB - Charge movement was measured in frog cut twitch fibers with the double Vaseline gap technique. Steady-state inactivation of charge movement was studied by changing the holding potential from -90 mV to a level ranging from -70 to -30 mV. Q beta and Q gamma at each holding potential were separated by fitting the Q-V plot with a sum of two Boltzmann distribution functions. At -70 mV Q beta and Q gamma were inactivated to 54.0% (SEM 2.2) and 82.7% (SEM 3.0) of the amounts at 90 mV. At holding potentials greater than or equal to -60 mV, more Q gamma was inactivated than Q beta, and at -30 mV Q gamma was completely inactivated but Q beta was not. There was no holding potential at which Q beta was unaffected and Q gamma was completely inactivated. The differences between the residual fractions of Q beta and Q gamma are significant at all holding potentials (P less than 0.001-0.05). The plot of the residual fraction of Q beta or Q gamma versus holding potential can be fitted well by an inverted sigmoidal curve that is a mirror image of the activation curve of the respective charge component. The pair of curves for Q gamma correlates well with those for tension generation or Ca release obtained by other investigators. The time courses of the inactivation of Q beta and Q gamma were studied by obtaining several Q-V plots with conditioning depolarizations lasting 1-20 s and separating each Q-V plot into Q beta and Q gamma components by fitting with a sum of two Boltzmann distribution functions. The inactivation time constant of Q beta was found to be 5-10 times as large as that of Q gamma. During repetitive stimulation, prominent I gamma humps could be observed in TEST-minus-CONTROL current traces and normal Q gamma components could be separated from the Q-V plots, whether 20 or 50 mM EGTA was present in the internal solution, whether 2 or 10 stimulations were used, and whether the stimuli were separated by 400 ms or 6 s. Repetitive stimulation slowed the kinetics of the I gamma hump and could shift the Q-V curve slightly in the depolarizing direction in some cases, resulting in an apparent suppression of charge at the potentials that fall on the steep part of the Q-V curve. PMID- 1640221 TI - Contribution of sarcolemmal sodium-calcium exchange and intracellular calcium release to force development in isolated canine ventricular muscle. AB - The aim of this work was to determine the relationship between peak twitch amplitude and sarcoplasmic reticulum (SR) Ca2+ content during changes of stimulation frequency in isolated canine ventricle, and to estimate the extent to which these changes were dependent upon sarcolemmal Na(+)-Ca2+ exchange. In physiological [Na+]o, increased stimulation frequency in the 0.2-2-Hz range resulted in a positive inotropic effect characterized by an increase in peak twitch amplitude and a decrease in the duration of contraction, measured as changes in isometric force development or unloaded cell shortening in intact muscle and isolated single cells, respectively. Action potentials recorded from single cells indicated that the inotropic effect was associated with a progressive decrease of action potential duration and a marked reduction in average time spent by the cell near the resting potential during the stimulus train. The frequency-dependent increase of peak twitch force was correlated with an increase of Ca2+ uptake into and release from the SR. This was estimated indirectly using the phasic contractile response to rapid (less than 1 s) lowering of perfusate temperature from 37 degrees C to 0-2 degrees C and changes of twitch amplitude resulting from perturbations in the pattern of electrical stimulation. Lowering [Na+]o from 140 to 70 mM resulted in an increase of contractile strength, which was accompanied by a similar increase of apparent SR Ca2+ content, both of which could be abolished by exposure to ryanodine (1 x 10( 8) M), caffeine (3 x 10(-3) M), or nifedipine (2 x 10(-6) M). Increased stimulation frequency in 70 mM [Na+]o resulted in a negative contractile staircase, characterized by a graded decrease of peak isometric force development or unloaded cell shortening. SR Ca2+ content estimated under identical conditions remained unaltered. Rate constants derived from mechanical restitution studies implied that the depressant effect of increased stimulation frequency in 70 mM [Na+]o was not a consequence of a decreased rate of refilling of a releasable pool of Ca2+ within the cell. These results demonstrate that frequency-dependent changes of contractile strength and intracellular Ca2+ loading in 140 mM [Na+]o require the presence of a functional sarcolemmal Na(+)-Ca2+ exchange process. The possibility that the negative staircase in 70 mM [Na+]o is related to inhibition of Ca(2+)-induced release of Ca2+ from the SR by various cellular mechanisms is discussed. PMID- 1640222 TI - On the mechanism of G protein beta gamma subunit activation of the muscarinic K+ channel in guinea pig atrial cell membrane. Comparison with the ATP-sensitive K+ channel. AB - The mechanism of G protein beta gamma subunit (G beta gamma)-induced activation of the muscarinic K+ channel (KACh) in the guinea pig atrial cell membrane was examined using the inside-out patch clamp technique. G beta gamma and GTP-gamma S bound alpha subunits (G alpha *'s) of pertussis toxin (PT)-sensitive G proteins were purified from bovine brain. Either in the presence or absence of Mg2+, G beta gamma activated the KACh channel in a concentration-dependent fashion. 10 nM G beta gamma almost fully activated the channel in 132 of 134 patches (98.5%). The G beta gamma-induced maximal channel activity was equivalent to or sometimes larger than the GTP-gamma S-induced one. Half-maximal activation occurred at approximately 6 nM G beta gamma. Detergent (CHAPS) and boiled G beta gamma preparation could not activate the KACh channel. G beta gamma suspended by Lubrol PX instead of CHAPS also activated the channel. Even when G beta gamma was pretreated in Mg(2+)-free EDTA internal solution containing GDP analogues (24-48 h) to inactivate possibly contaminating G i alpha *'s, the G beta gamma activated the channel. Furthermore, G beta gamma preincubated with excessive GDP-bound G o alpha did not activate the channel. These results indicate that G beta gamma itself, but neither the detergent CHAPS nor contaminating G i alpha *, activates the KACh channel. Three different kinds of G i alpha * at 10 pM-10 nM could weakly activate the KACh channel. However, they were effective only in 40 of 124 patches (32.2%) and their maximal channel activation was approximately 20% of that induced by GTP-gamma S or G beta gamma. Thus, G i alpha * activation of the KACh channel may not be significant. On the other hand, G i alpha *'s effectively activated the ATP-sensitive K+ channel (KATP) in the ventricular cell membrane when the KATP channel was maintained phosphorylated by the internal solution containing 100 microM Mg.ATP. G beta gamma inhibited adenosine or mACh receptor mediated, intracellular GTP-induced activation of the KATP channel. G i alpha *'s also activated the phosphorylated KATP channel in the atrial cell membrane, but did not affect the background KACh channel. G beta gamma subsequently applied to the same patch caused prominent KACh channel activation. The above results may indicate two distinct regulatory systems of cardiac K+ channels by PT-sensitive G proteins: G i alpha activation of the KATP channel and G beta gamma activation of the KACh channel. PMID- 1640224 TI - Brain mapping--a useful tool or a dangerous toy? PMID- 1640223 TI - Separation of Q beta and Q gamma charge components in frog cut twitch fibers with tetracaine. Critical comparison with other methods. AB - Charge movement was measured in frog cut twitch fibers with the double Vaseline gap technique. 25 microM tetracaine had very little effect on the maximum amounts of Q beta and Q gamma but slowed the kinetics of the I gamma humps in the ON segments of TEST-minus-CONTROL current traces, giving rise to biphasic transients in the difference traces. This concentration of tetracaine also shifted V gamma 3.7 (SEM 0.7) mV in the depolarizing direction, resulting in a difference Q-V plot that was bell-shaped with a peak at approximately -50 mV. 0.5-1.0 mM tetracaine suppressed the total amount of charge. The suppressed component had a sigmoidal voltage distribution with V = -56.6 (SEM 1.1) mV, k = 2.5 (SEM 0.5) mV, and qmax/cm = 9.2 (SEM 1.5) nC/microF, suggesting that the tetracaine-sensitive charge had a steep voltage dependence, a characteristic of the Q gamma component. An intermediate concentration (0.1-0.5 mM) of tetracaine shifted V gamma and partially suppressed the tetracaine-sensitive charge, resulting in a difference Q V plot that rose to a peak and then decayed to a plateau level. Following a TEST pulse to greater than -60 mV, the slow inward current component during a post pulse to approximately -60 mV was also tetracaine sensitive. The voltage distribution of the charge separated by tetracaine (method 1) was compared with those separated by three other existing methods: (a) the charge associated with the hump component separated by a sum of two kinetic functions from the ON segment of a TEST-minus-CONTROL current trace (method 2), (b) the steeply voltage dependent component separated from a Q-V plot of the total charge by fitting with a sum of two Boltzmann distribution functions (method 3), and (c) the sigmoidal component separated from the Q-V plot of the final OFF charge obtained with a two pulse protocol (method 4). The steeply voltage-dependent components separated by all four methods are consistent with each other, and are therefore concluded to be equivalent to the same Q gamma component. The shortcomings of each separation method are critically discussed. Since each method has its own advantages and disadvantages, it is recommended that, as much as possible, Q gamma should be separated by more than one method to obtain more reliable results. PMID- 1640225 TI - Johannes Kepler 1571-1630. PMID- 1640226 TI - Enhanced physical therapy improves recovery of arm function after stroke. A randomised controlled trial. AB - Previous research on stroke rehabilitation has not established whether increase in physical therapy lead to better intrinsic recovery from hemiplegia. A detailed study was carried out of recovery of arm function after acute stroke, and compares orthodox physiotherapy with an enhanced therapy regime which increased the amount of treatment as well as using behavioural methods to encourage motor learning. In a single-blind randomised trial, 132 consecutive stroke patients were assigned to orthodox or enhanced therapy groups. At six months after stroke the enhanced therapy group showed a small but statistically significant advantage in recovery of strength, range and speed of movement. This effect seemed concentrated amongst those who had a milder initial impairment. More work is needed to discover the reasons for this improved recovery, and whether further development of this therapeutic approach might offer clinically significant gains for some patients. PMID- 1640227 TI - The Scottish Motor Neuron Disease Register: a prospective study of adult onset motor neuron disease in Scotland. Methodology, demography and clinical features of incident cases in 1989. AB - The Scottish Motor Neuron Disease Register (SMNDR) is a prospective, collaborative, population based study of motor neuron disease (MND) in Scotland. The register started in January 1989 with the aim of studying the clinical and epidemiological features of MND by prospectively identifying incident patients. It is based on a system of registration by recruitment from multiple sources, followed by the collection of complete clinical data and follow up, mainly through general practitioners. In this report the register's methodology and the demography and incidence data for the first year of study are presented. One hundred and fourteen newly diagnosed patients were identified in 1989 giving a crude incidence for Scotland of 2.24/100,000/year. Standardised incidence ratios showed a non-significant trend towards lower rates in north eastern regions and island areas. PMID- 1640228 TI - Suicide and multiple sclerosis: an epidemiological investigation. AB - In a nationwide investigation the risk of death by suicide for patients with multiple sclerosis (MS) was assessed using records kept at the Danish Multiple Sclerosis Registry (DMSR) and the Danish National Register of Cause of Death. The investigation covers all MS patients registered with DSMR with an onset of the disease within the period 1953-85, or for whom MS was diagnosed in the same period. Fifty three of the 5525 cases in the onset cohort group committed suicide. Using the figures from the population death statistics by adjustment to number of subjects, duration of observation, sex, age, and calendar year at the start of observation, the expected number of suicides was calculated to be nearly 29. The cumulative lifetime risk of suicide from onset of MS, using an actuarial method of calculation, was 1.95%. The standard mortality ratio (SMR) of suicide in MS was 1.83. It was highest for males and for patients with onset of MS before the age of 30 years and those diagnosed before the age of 40. The SMR was highest within the first five years after diagnosis. PMID- 1640229 TI - Primary intracerebral haemorrhage in the Jyvaskyla region, central Finland, 1985 89: incidence, case fatality rate, and functional outcome. AB - The age and sex specific incidence rates, the case fatality rates, and the functional outcome of patients with primary intracerebral haemorrhage occurring in a population of 116,000 during a period of four years four months are presented. A total of 158 patients were identified, the diagnosis was confirmed in 78% by CT, and in 22% by necropsy. The crude annual incidence rate was 31/100,000 population, the age specific rates increased from two to 222/100,000 from the age of 30-39 to over 80 years. Men had higher incidence rates between the ages of 40 and 79 years. The short term case fatality rate was high, 27% of patients dying during the first day after onset of symptoms, and 50% were dead at 30 days. After the first month the probability of survival did not differ from an age- and sex-matched average population. Large haematoma volume had an adverse effect on the short term, old age (greater than 70 years) on the long term survival. Ventricular extension, especially when combined with hydrocephalus was a bad omen for short term survival. Infratentorial and large basal ganglionic haematomas, and primary intraventricular haemorrhage carried a worse prognosis than haematomas of other locations. At the end of a median 32 month follow up 55 (35%) of the patients were alive, 51% of these were independent in activities of daily living, 45% were dependent on outside help, and 4% needed constant nursing care. Old age (greater than 70 years), but not the haematoma volume or location, was associated with a poor functional recovery. PMID- 1640230 TI - Endoneurial capillary abnormalities in mild human diabetic neuropathy. AB - Microvascular factors have been implicated in the pathogenesis of human diabetic neuropathy. The extent of microangiopathy was assessed in 15 diabetic patients with clinically mild neuropathy and compared with eight age matched control subjects. Endoneurial capillary density was reduced (p less than 0.04) and correlated significantly with reduced myelinated fibre density (p less than 0.01). Both basement membrane area (p less than 0.0001) and endothelial cell profile number per capillary (p less than 0.002) were significantly increased in diabetic patients and correlated significantly with both neurophysiological and neuropathological measures of neuropathic severity. There was no evidence of endothelial cell hypertrophy as assessed by either cross sectional endothelial cell area or a reduction in luminal size. Furthermore, the percentage of closed vessels did not differ between diabetic patients and control subjects and failed to relate to measures of neuropathic severity. It was concluded that microvascular abnormalities are prominent in patients with clinically mild human diabetic neuropathy, and that these data provide further support for the role of endoneurial capillary disease in the development of this condition. PMID- 1640231 TI - Directional hypokinesia in spatial hemineglect: a case study. AB - A patient with an ischaemic lesion involving the right frontal lobe and basal ganglia showed left spatial hemineglect in visuomotor exploratory tasks, requiring the use of the right unaffected hand. Her performance was, however, entirely preserved, with no evidence of neglect, when she was required to identify targets among distractors in both the left and right halves of space, and in the Wundt-Jastrow illusion test. The latter tasks do not require any arm movement in extrapersonal space. In this patient spatial hemineglect may be explained in terms of defective organisation of movements towards the left half space (directional hypokinesia). The frontal lesion of the patient may be the neural correlate of this selective disorder. This pattern of impairment may be contrasted with the typical deficit found in patients with right brain damage with perceptual neglect. One case had a defective performance both in visuomotor and in purely perceptual tasks. PMID- 1640232 TI - A controlled, longitudinal study of dementia in Parkinson's disease. AB - Serial assessments of cognition, mood, and disability were carried out at nine month intervals over a 54 month period on a cohort of 87 patients with Parkinson's disease (PD) and a matched cohort of 50 control subjects. Dementia was diagnosed from data by rigorously applying DSM-III-R criteria. Initially, 6% (5/87) PD patients were demented, compared with none of the 50 control subjects. A further 10 PD patients met the dementia criteria during the follow up period; this was equivalent, with survival analysis, to a cumulative incidence of 19%. With the number of person years of observation as the denominator, the incidence was 47.6/1000 person years of observation. None of the control subjects fulfilled dementia criteria during the follow up period. The patients with PD who became demented during follow up were older at onset of Parkinson's disease than patients who did not become demented, had a longer duration of Parkinson's disease, and were older at inclusion to the study. PMID- 1640233 TI - A component analysis of the generation and release of isometric force in Parkinson's disease. AB - Paradigms of isometric force control allow study of the generation and release of movement in the absence of complications due to disordered visuomotor coordination. The onset and release of isometric force in Parkinson's disease (PD) was studied, using computerised determinants of latency of response and rate of force generation and release. Components of isometric force control were related to measures of cognitive, affective and clinical motor disability. The effects of treatment were determined by longitudinal study of de novo patients. Patients with PD showed impairment in latency and rate of force change for movement release as well as onset. Rate of force change correlated with depression, clinical motor disability and memory quotient but latency showed no correlation with any of these measures. Treatment improved rate of force release, in concert with clinical motor disability, but not latency. These results suggest dissociations between latency and rate of force change that may be linked to different neurochemical deficits. Further, they demonstrate akinetic deficits in force release that argue against the "neural energy hypothesis" of akinesia. PMID- 1640234 TI - Progressive anarthria with secondary parkinsonism: a clinico-pathological case report. AB - The pathological process and lesion topography in patients with the syndrome of progressive aphasia are heterogeneous and few necropsy examination cases have been investigated. This is a case report of a 53 year old right handed man with progressive anarthria and secondary Parkinsonism over a period of six years. Positron emission tomography (PET) showed a decreased cerebral blood flow and metabolism in the frontal cortex, which was more pronounced on the left. Neuropathology disclosed a spongiform vacuolation in layer II of the frontal cortex, mostly in the Broca area, and neuronal loss in the substantia nigra. This original case reinforces the view that there are different entities of the syndrome of progressive aphasia which can be identified on the basis of clinical, neuroimaging and anatomical data. PMID- 1640235 TI - Hemiataxia-hypesthesia: a thalamic stroke syndrome. AB - Six patients had isolated hemiataxia and ipsilateral sensory loss, as a manifestation of thalamic infarction in the thalamogeniculate territory. Acute hemiataxia-hypesthesia was not found in 1075 other patients from the Lausanne Stroke Registry who were admitted during the same period. Stroke onset was progressive in five patients and immediately complete in one. Five patients had an objective sensory loss. In two patients this affected light touch, pain and temperature sense, and in another three light touch, pain temperature, position and vibration sense. One patient had a purely subjective sensory disturbance. The sensory deficit cleared or was clearing although the ataxia persisted in all patients. On lesion mapping on CT or MRI, all patients had involvement of the lateral part of the thalamus (ventral posterior nucleus and ventral lateral nucleus). The presumed causes of stroke were cardioembolism in one patient, posterior cerebral artery occlusion in one patient and meningovascular syphilis in one patient, hypertensive small vessel disease in two patients, and undetermined in one patient. Hemiataxia-hypesthesia is a new stroke syndrome involving the perforating branches to the lateral thalamus, but in which small vessel disease may not be the leading cause. PMID- 1640236 TI - Risk of sudden death during sleep in syringomyelia and syringobulbia. AB - Clinical, respiratory, and polysomnographic findings in three patients with syringomyelia and syringobulbia who developed severe respiratory complications are described. Neurological examination showed evidence of IXth and Xth cranial nerve involvement with dysphagia and dysphonia, but there were no complaints of serious sleep difficulties. Two patients died during sleep and the other was resuscitated during a nap. All patients showed moderate restrictive ventilatory defects with reduced maximal buccal pressures and one also showed a low ventilatory response to CO2 rebreathing. Protracted central, obstructive, and mixed apnoeas and hypopnoeas were commonly observed during sleep. There were no changes in heart rate during these events. A combination of respiratory and cardiovascular mechanisms might have been responsible for the severe complications described. PMID- 1640237 TI - Stereotactic linac radiosurgery for arteriovenous malformations. AB - Stereotactic linear accelerator (linac) radiosurgery has been in operation in the West Midlands since 1987, the first of its kind in the United Kingdom. Forty two patients with high-flow cerebral arteriovenous malformations have been treated, 26 of whom have been followed up. Angiography one year after treatment showed that five lesions were obliterated, 11 were reduced in size and/or flow rate and 10 were unchanged. Overall results show that nine out of 10 patients reviewed at 24 months had total obliteration. Three patients had complications; one has fully recovered, one died of an unrelated cause at 36 months and the other died from recurrent haemorrhage at nine months. Two patients had recurrent non-fatal haemorrhage within 24 months of treatment; both recovered without further deficit. All patients are fit to work but eight are unemployed. Although the follow up period is short, the early results indicate a success rate similar to those published by others using linac radiosurgery. PMID- 1640238 TI - Cerebral blood flow, arteriovenous oxygen difference, and outcome in head injured patients. AB - Cerebral blood flow (CBF) and other physiological variables were measured repeatedly for up to 10 days after severe head injury in 102 patients, and CBF levels were related to outcome. Twenty five of the patients had a reduced CBF [mean (SD) 0.29 (0.05) ml/g/min]; 47 had a normal CBF, (0.41 (0.10) ml/g/min); and 30 had a raised CBF (0.62 (0.14) ml/g/min). Cerebral arteriovenous oxygen differences were inversely related to CBF and averaged 2.1 (0.7) mumol/ml in the group with reduced CBF, 1.9 (0.5) mumol/ml in the group with normal CBF, and 1.6 (0.4) mumol/ml in the group with raised CBF. Patients with a reduced CBF had a poorer outcome than patients with a normal or raised CBF. Mortality was highest in patients with a reduced CBF, and was 32% at three months after injury, whereas only 21% of the patients with a normal CBF and 20% of the patients with a raised CBF died. There were no differences in the type of injury, initial score on the Glasgow Coma Scale, mean intracranial pressure (ICP), highest ICP, or the amount of medical treatment required to keep the ICP less than 20 mm Hg in each group. Systemic factors did not significantly contribute to the differences in CBF among the three groups. A logistic regression model of the effect of CBF on neurological outcome was developed. When adjusted for variables which were found to be significant confounders, including age, initial Glasgow Coma Score, haemoglobin concentration, cerebral perfusion pressure and cerebral metabolic rate of oxygen, a reduced CBF remained significantly associated with an unfavourable neurological outcome. PMID- 1640239 TI - Cervical myelopathy due to nuclear herniations in young adults: clinical and radiological profile, results of microdiscectomy without interbody fusion. AB - A study was made of the clinical and radiological characteristics and the results of microsurgical discectomy without interbody fusion, of 26 young adults, who presented with cervical myelopathy due to nuclear herniations. Neck trauma was not a significant aetiological factor. The disease produced moderate to very severe functional disability in most patients (73%), in a relatively short period (mean symptom duration 6.3 months). Radiological assessment revealed the presence of canal stenosis, significant disc protrusions with paucity of spondylotic changes in most patients. At operation, soft disc lesions were found in 85% and sequestrated discs in 31%. Microsurgical discectomy without fusion produced gratifying recovery of functional disability without significant deleterious effects on the cervical spine. PMID- 1640240 TI - Somatosensory and brainstem auditory evoked potential in congenital craniovertebral anomaly; effect of surgical management. AB - Clinical features and evoked potential recordings were analysed in 32 patients with congenital atlantoaxial dislocation before and after surgery. Seven patients (group 1) had atlantoaxial dislocation, while 22 patients had associated basilar invagination (group 2). In both groups, pyramidal tract signs, posterior column signs, wasting of the upper limbs, and abnormality of somatosensory evoked potentials (SSEP) were similar. Conversely, lower cranial nerve involvement and abnormal brainstem auditory evoked potentials (BAEP) were significantly more in patients with basilar invagination (p less than 0.05). All seven patients in group 1 and 17 patients in group 2 were operated upon. Clinical and electrophysiological deterioration were significant in patients with basilar invagination (group 2), following posterior fixation compared with group 1. Among the patients in group 2, who clinically deteriorated following posterior fixation, seven had transoral excision of odontoid and six of them improved both clinically and electrophysiologically. Two patients in group 2 had odontoid excision before posterior fixation, and in both the evoked potentials improved postoperatively. In group 1 the patient's BAEP remained unaffected following posterior fixation, however, in group 2, eight patients over 53% showed improvement in brainstem function following posterior fixation. This study shows the value of evoked potentials in congenital atlantoaxial dislocation, and rationalizes the surgical procedure in these patients. In patients with basilar invagination, odontoid excision is the preferred first stage procedure. PMID- 1640241 TI - Cerebellar syndrome in myxoedema revisited: a published case with carcinomatosis and multiple system atrophy at necropsy. AB - One of six patients in a 1960 paper on "Cerebellar syndrome in myxoedema" was subsequently found to have adenocarcinoma. General post-mortem revealed carcinomatosis and basal pneumonia. Neuropathological examination revealed the changes of multiple system atrophy. The relationship between hypothyroidism, carcinoma, and cerebellar, pontine and striatonigral degeneration is discussed. PMID- 1640242 TI - Histoplasmosis of the central nervous system. AB - Histoplasma capsulatum infection of the central nervous system is extremely rare in the United Kingdom partly because the organism is not endemic. However, because the organism can remain quiescent in the lungs or the adrenal glands for over 40 years before dissemination, it increasingly needs to be considered in unexplained neurological disease particularly in people who lived in endemic areas as children. In this paper a rapidly progressive fatal myelopathy in an English man brought up in India was shown at necropsy to be due to histoplasmosis. The neurological features of this infection are reviewed. PMID- 1640243 TI - IgA producing primary intracerebral lymphoma. AB - The first case of a primary and solitary IgA (lambda) producing tumour (possibly a non-Hodgkin's lymphoma) in the CNS is reported. Clinical and neuroimaging findings are described. Early diagnosis without brain biopsy and successful therapy were possible by CSF and serum immunoglobulin analysis which proved local paraprotein production restricted to the CNS. PMID- 1640245 TI - Cocaine abuse simulating the aura of migraine. PMID- 1640244 TI - Spasms of amputation stumps. AB - Two patients are presented with muscle spasms in an amputation stump. Neither patient experienced neuropathic pain nor phantom sensations, though phantom sensory phenomena, severe pain, and lack of response to treatment is characteristic of reported cases. One patient, a 75 year old man, has had myoclonic activity of the stump for more than two years, and the other, a 79 year old woman, recovered spontaneously after three months and is symptom free after a one year follow up. We emphasise the lack of association with pain and the need to consider spontaneous improvement when therapy is evaluated. PMID- 1640246 TI - Pathological laughter and brain stem glioma. PMID- 1640247 TI - Post radiation monomelic amyotrophy. PMID- 1640248 TI - Sellar tuberculoma. PMID- 1640249 TI - Posterior ischaemic optic neuropathy after a spontaneous extradural haematoma. PMID- 1640250 TI - Central pontine myelinolysis in a patient with AIDS. PMID- 1640251 TI - Could midbrain "resting" tremor be caused by postural maintenance at rest? PMID- 1640252 TI - Transcutaneous phrenic nerve stimulation. PMID- 1640253 TI - Dietary lipid regulates the amount and functional state of UDP glucuronosyltransferase in rat liver. AB - The effect of a fat-free diet on the amount and functional state of UDP glucuronosyltransferase was studied in rat liver microsomes. Measurements of enzyme activity showed that activity was approximately 30% lower in untreated microsomes in response to the fat-free diet as compared with the control diet. Immunoblotting with anti-UDP-glucuronosyltransferase showed approximately 200% less enzyme in rats fed the fat-free diet. A kinetic method for measuring total UDP-glucuronosyltransferase confirmed the result of the immunoblot. Thus, the total amount of enzyme declined to a greater extent than enzyme activity. Responses of the enzyme to activation by palmitoyl-lysophosphatidylcholine or UDP N-acetyl-glucosamine suggested that rats fed the fat-free diet had a greater activity per molecule of UDP-glucuronosyltransferase than did rats fed the control diet. This result explained the relatively small decline in enzyme activity as compared with enzyme concentration in microsomes prepared from animals fed the fat-free diet. Fatty acid analysis of microsomal lipids demonstrated that the fat-free diet was associated with lower levels of arachidonic and linoleic acids and greater amounts of palmitoleic, oleic and cis vaccenic acids. PMID- 1640254 TI - Developmental stages and energy restriction affect cellular oncogene expression in tissues of female rats. AB - The influence of developmental stages and energy restriction on c-Ha-ras and c fos cellular oncogene mRNA level was examined in mammary tissue and liver of female rats. c-Ha-ras and c-fos RNA transcripts in mammary tissue peaked at 9 wk of age, decreased during pregnancy, were lowest at mid-lactation and then increased at 25 wk. c-Ha-ras in liver showed highest expression at 5 wk and was hardly detectable at 11 wk, mid-pregnancy, mid-lactation and 25 wk. Liver c-fos and c-Ha-ras mRNA levels were similar. Lower c-Ha-ras and c-fos mRNA levels were observed in mammary tissue of energy-restricted (to 70% of ad libitum intake) rats at 25 wk compared with those allowed ad libitum access to food. Energy restriction did not affect liver c-Ha-ras and c-fos mRNA levels throughout the experimental period. These results demonstrate that developmental stages and energy restriction affect cellular oncogene mRNA levels with tissue-specific patterns. PMID- 1640255 TI - Dietary selenium stabilizes glutathione peroxidase mRNA in rat liver. AB - The objective of these studies was to determine the step at which dietary selenium (Se) regulates the pre-translational expression of the gene for cytosolic Se-glutathione peroxidase (Se-GPX) in rat liver. Weanling male Sprague Dawley rats were fed a Torula yeast-based Se-deficient diet, or the same diet supplemented with 0.5 mg/kg as Na2SeO3, for at least 40 d. Livers were excised and divided into three portions for isolation of nuclei, for purification of total RNA and for assay of Se-GPX activity. Nuclei were used in run-on transcription assays and for isolation of total nuclear RNA. Nuclear RNA and total liver RNA were probed with segments from a rat Se-GPX cDNA in Northern blot and slot blot assays. Despite marked differences in Se-GPX activity, there were no significant differences between dietary groups in the transcription rates of the Se-GPX gene. Species hybridizing to Se-GPX were not detected in nuclear RNA. However, steady state levels of Se-GPX mRNA were markedly reduced by Se deficiency. These results suggest that dietary Se exerts its effect on pretranslational Se-GPX gene expression at the level of cytosolic mRNA stabilization. PMID- 1640256 TI - Lung eicosanoid synthesis is affected by age, dietary fat and vitamin E. AB - The effect of age, dietary fat type and all-rac-alpha-tocopheryl acetate (vitamin E) supplementation on ex vivo synthesis of lung eicosanoids was measured in C57BL/6NIA mice using a 2 (age) x 3 (fat) x 3 (vitamin E) factorial design. Young (3-mo-old) and old (24-mo-old) mice were fed a semipurified diet containing 5% (by wt) corn oil, coconut oil or fish oil supplemented with 30, 100 or 500 mg vitamin E/kg for 4 wk. Ex vivo synthesis of thromboxane B2 (TXB2) and 6-keto prostaglandin F1 alpha (PGI2) were measured by RIA in lung homogenates. Old mice had significantly higher concentrations of TXB2 and PGI2 than did young mice, resulting in a significant increase in the TXB2:PGI2 ratio with aging. Young and old mice fed fish oil had significantly lower concentrations of PGI2 and TXB2 than those fed corn oil or coconut oil. The degree of reduction varied according to age and vitamin E status. Old mice fed fish oil and 30 mg vitamin E/kg diet had the lowest plasma vitamin E concentration and the highest TXB2:PGI2 ratio. The TXB2:PGI2 ratio was significantly reduced in old mice fed coconut oil or fish oil by vitamin E supplementation. Vitamin E supplementation (100 mg/kg) significantly increased PGI2 concentration in young mice fed coconut oil. Thus, significant changes in the capacity of lung to synthesize eicosanoids occur with age and are influenced by dietary fat type and vitamin E. J. Nutr. PMID- 1640257 TI - Lymph chylomicron size is modified by fat saturation in rats. AB - Mesenteric lymph chylomicrons were characterized during and after the establishment of steady-state triglyceride transport. Chylomicrons were isolated from lymph at 0, 2, 4, 6, 8 and 12 h after the start of an 8-h infusion of triglyceride emulsion (prepared using either corn or butter oil) at 160 mumol/(kg.h). Lymph flow was not influenced by triglyceride source. Output of triglyceride, measured both in whole lymph and in the chylomicron fraction, was not significantly affected by triglyceride source. Butter oil infusion produced a higher output of chylomicron phospholipid and unesterified cholesterol than was observed in response to corn oil emulsion. Ratios of transported phospholipid to triglyceride for butter oil chylomicrons were higher (1.3- to 1.7-fold) than those for corn oil chylomicrons at every time point examined after the start of lipid infusion. No other compositional differences in chylomicrons due to triglyceride source were observed. These results support the hypothesis that differences in efficiency of absorption and transport between saturated and unsaturated fat are sufficient to explain size differences in secreted chylomicrons in response to corn and butter oil infusions, and suggest that chylomicron number may be influenced by dietary fat saturation. PMID- 1640259 TI - Meats and fish consumed in the American diet contain substantial amounts of ether linked phospholipids. AB - The primary goal of this study was to determine the amounts of ether-containing phospholipids, along with their concentration of certain polyunsaturated acyl groups, from selected, commonly consumed foods of animal origin (salmon, catfish, pork, beef, turkey and chicken). Levels of ether-linked glycerolipids in the samples were of particular interest, because ingestion of ether lipids could contribute to the production of platelet-activating factor (PAF; 1-alkyl-2-acetyl sn-glycero-3-phosphocholine), one of the most potent biological mediators known. Alkylacyl-sn-glycero-3-phosphocholine was found in all of the meats, with pork loin having the highest levels (0.9 mumol/g tissue) and chicken breasts the lowest (0.1 mumol/g tissue). Although choline plasmalogens were not as evident as the ubiquitous ethanolamine plasmalogens, substantial amounts (1.0 mumol/g tissue) of alk-1-enylacyl-sn-glycero-3-phosphocholine were found in tissues from beef and turkey. Triacylglycerols contained greater proportions of saturated fatty acids than phospholipids, and the ether-linked phospholipids were generally more unsaturated than diacyl species of the same phospholipid. Our data indicate that in addition to the phospholipid fraction of commonly eaten animal tissues supplying substantial amounts of polyunsaturated fatty acids, they are also a rich source of ether-linked lipids. Dietary ether-linked phospholipids could influence the lipid composition of host tissues to the extent that biological responses produced by ether lipid mediators would be affected. PMID- 1640258 TI - Prolonged lactation contributes to depletion of maternal energy reserves in Filipino women. AB - This paper identifies determinants of women's postpartum weight and weight change in a large group of Filipino women followed for 24 mo. Longitudinal, multivariate models focused on the effects of lactation, while controlling for energy intake, energy expenditure, reproductive history and seasonality. Lactation was found to have a significant negative effect on weight of urban women. The negative effects of lactation increased with the intensity and duration of breast-feeding. Among rural women negative effects of lactation on weight were observed only after 10 14 mo. Models of net postpartum weight change (from 2 to 24 mo) among nonpregnant women confirmed an important role for lactation. The likelihood of weight loss was significantly increased by lactation of more than 12-mo duration, by greater maternal age and by low dietary energy intake. The effects of lactation on maternal energy reserves can be mitigated substantially be increasing maternal dietary energy intakes. PMID- 1640260 TI - Dietary fatty acids temporarily alter liver very long-chain fatty acid composition in mice. AB - To determine the influence of dietary fatty acids on tissue very long-chain fatty acid (VLFA) composition, mice were fed four diets containing 15 g fat/100 g diet derived largely from either safflower oil, peanut oil, olive oil or glycerol trioleate oil. The diets varied widely in the composition of VLFA and other fatty acids. Digestibility of total dietary VLFA ranged from 84.6% in mice fed the glycerol trioleate diet to 96.7% in those fed the safflower oil diet. After 3 mo, the saturated VLFA composition of liver total lipids and sphingomyelin was lower in animals fed the glycerol trioleate oil diet than in mice fed most other diets. Although the saturated VLFA content of the peanut oil diet was more than 15-fold greater than that of the other diets, animals fed the peanut oil diet showed little or no selective increase in liver saturated VLFA. The VLFA composition of brain was comparable in all dietary groups. After 8 mo of feeding, the liver saturated VLFA composition tended to increase and differences between groups disappeared. Liver peroxisomal beta-oxidation of lignocerate (24:0) was similar among all dietary groups. These results demonstrate that dietary fatty acids shorter than VLFA temporarily influence the saturated VLFA composition of liver. PMID- 1640261 TI - Administration modalities and intestinal lymph absorption of arachidonic acid in rats. AB - We investigated the effects of the proportion of arachidonic acid on lymph lipoprotein synthesis in rats, when infused in the presence of lipids with varying degrees of saturation. A single dose of 90 mumol of lipid was administered intraduodenally and intestinal lymph was collected. Emulsion lipid constituents were 90 mumol of [14C]arachidonic acid alone, or either 30 mumol of [14C]arachidonic acid or 5 mumol of [14C]arachidonic acid and 25 mumol of linoleic acid, with 30 mumol of a free fatty acid and 30 mumol of a monoglyceride (the more saturated: oleic acid + monopalmitin; the more unsaturated: linoleic acid + monoolein). Radioactive lymph recovery of [14C]arachidonic acid infused alone reached 32.6 +/- 1.3% of the radioactivity administered and the presence of another fatty acid and a monoglyceride increased it from 38.7 +/- 2.6 to 51.9 +/- 1.1%. For 30 mumol of arachidonic acid, integration into lymph phospholipids was higher when arachidonic acid was infused with oleic acid and monopalmitin than with linoleic acid and monoolein (7.3 +/- 2.7 and 2.8 +/- 0.2% at the absorption peaks, respectively), and it was 4.8 +/- 0.5% when arachidonic acid was infused alone. For 5 mumol of arachidonic acid, the degree of unsaturation of the added lipid did not modify phospholipid incorporation, which was maintained at 6.9 to 7.2%. The proportion and size of chylomicrons increased with the degree of lipid emulsion unsaturation. Percentages of [14C]phospholipids and of chylomicrons were highly correlated. The proportion of arachidonic acid and degree of lipid emulsion unsaturation affected lymphatic arachidonic acid absorption modalities. PMID- 1640262 TI - Inbred strains of rats have differential sensitivity to dietary phosphorus induced nephrocalcinosis. AB - The degree of nephrocalcinosis after increasing the dietary phosphorus concentration from 0.2 to 0.5 g/100 g was measured in weanling female rats of 10 inbred strains. Based on kidney calcium concentrations and histological kidney calcification scores, there were considerable strain differences in nephrocalcinogenesis; 86% of the strain variability in nephrocalcinosis was attributable to genetic factors. Two strains with the most extreme nephrocalcinogenic responses were retested and the strain difference was found to be reproducible. Mean plasma phosphorus concentrations after phosphorus feeding were lower in the sensitive strain than in the insensitive strain. The high phosphorus diet produced greater urinary phosphorus concentrations, with the increase being greater in the sensitive strain. The strain difference in the response of urinary phosphorus concentrations after raising dietary phosphorus level may determine the strain difference in phosphorus-induced nephrocalcinosis. After consuming the high phosphorus diet, RP rats housed in groups in solid floored cages had significantly higher degrees of nephrocalcinosis than their counterparts housed individually in metabolism cages with wire-mesh bases. PMID- 1640263 TI - The splanchnic organs, liver and kidney have unique roles in the metabolism of sulfur amino acids and their metabolites in rats. AB - The arterial-venous differences for methionine and cysteine and their metabolites, glutathione, taurine and sulfate, were measured across the splanchnic organs, the liver, the kidney and the hindlimb of fed rats. Methionine and cysteine were released into the blood by the splanchnic organs and removed by the liver. These results indicate that more than half of the sulfur amino acids taken up by the liver were used for synthesis of glutathione for export into the plasma. The kidney removed about half of the glutathione exported by the liver, presumably due to action of gamma-glutamyl transpeptidase and dipeptidase, and released to the circulation a comparable amount of cysteine. Taurine, presumably from deconjugation of bile acids, was released into the plasma by the splanchnic organs; taurine was also released by the liver. The hepatosplanchnic release of taurine into the plasma indicates that the liver is the major site of taurine biosynthesis; taurine was removed by the kidney for excretion in the urine. A small amount of methionine was removed by the kidney, and the hindlimb released a small amount of glutathione and methionine into the plasma. The splanchnic organs seemed to remove substantial sulfate from the plasma in addition to that provided by the diet, and a net release of sulfate from the liver was observed. The relative roles of the various tissues in sulfate production and removal was not clear from these studies, due to the large variability in the arterial-venous differences observed. PMID- 1640264 TI - Medium-chain triacylglycerols enhance release of cholecystokinin in chicks. AB - Whether medium-chain triacylglycerols (MCT) affect the plasma concentration of cholecystokinin (CCK) and crop-emptying rate in chicks was investigated after 0, 30, 60, 90, 120 or 180 min of diet intubation. Triacylglycerol sources used were corn oil [containing long-chain triacylglycerols (LCT)], glyceryl tricaprate and glyceryl tricaprylate at a level of 200 g/kg diet. Plasma CCK concentration was significantly enhanced in chicks given the two MCT treatments, but not in those given the LCT treatment, after 30 min feeding relative to the initial level. At all time points, chicks fed the diet containing LCT had significantly lower plasma CCK concentrations than those fed MCT, and chicks fed glyceryl tricaprate had higher concentrations than those fed glyceryl tricaprylate. Dietary MCT sources significantly delayed diet passage from the crop compared with dietary LCT. These results indicate that MCT are more potent stimulators of CCK secretion in chicks than LCT. PMID- 1640265 TI - Increases in serum sphingosine and sphinganine and decreases in complex sphingolipids in ponies given feed containing fumonisins, mycotoxins produced by Fusarium moniliforme. AB - Consumption of food contaminated with Fusarium moniliforme causes leucoencephalomalacia and hepatotoxicity in horses, pulmonary edema in pigs and liver cancer in rats, and has been correlated with esophageal cancer in humans. The causative agents are thought to be a family of compounds called fumonisins, which have recently been shown to be potent inhibitors of sphingosine (sphinganine) N-acyltransferase. Because inhibition at this step blocks the formation of complex sphingolipids while leading to accumulation of sphinganine, we hypothesized that exposure of animals to fumonisin-contaminated feed might be detected by analyses of serum sphingolipids. Within days of giving ponies feed contaminated with 15 to 44 micrograms/g fumonisin B1, there was an increase in the amount of free sphinganine (and sometimes sphingosine) and a reduction in complex sphingolipids. Free sphinganine and sphingosine decreased when ponies consumed less of the contaminated feed, and increased again when they consumed more fumonisin. When toxicosis was evident as indicated by other serum markers, complex sphingolipids as well as free sphingosine and sphinganine were elevated, probably due to loss of sphingolipids from dying cells. These findings establish that consumption of fumonisin-contaminated feed disrupts sphingolipid metabolism. Because the changes in sphinganine and sphingosine were seen before liver enzymes were noticeably elevated, they may be an early marker of exposure to fumonisins. PMID- 1640266 TI - Abomasal infusion of casein enhances nitrogen retention in somatotropin-treated steers. AB - The effects of bovine somatotropin (bST) administration and abomasal protein infusion on nitrogen metabolism were investigated using four abomasally cannulated Holstein steers in a 4 x 4 Latin square design. Treatments were factorially arranged to include daily abomasal infusion (water or casein, 0.9 g/kg body wt) and daily bST injection (0 or 200 micrograms/kg body wt). Each treatment period lasted for 23 d and consisted of an adjustment period (d 1 to 7), casein infusion (d 8 to 23) and bST treatment (d 10 to 23). Nitrogen metabolism and serum insulin-like growth factor-I (IGF-I) profiles were characterized on d 16-22. Animals were fed a total mixed diet balanced to achieve 0.75 kg gain/d and supplemented to provide 115% of requirements for crude protein and minerals. Nitrogen retention was increased by casein and bST individually (21 and 33%, respectively) or in combination (75%). Somatotropin treatment increased the biological value of absorbed N, which was consistent with reductions in plasma urea nitrogen. Circulating IGF-I was increased by bST and was highly correlated (r = 0.73) with N retention. Overall, bST altered requirements so that less absorbed N was required per unit of N retained. However, results also demonstrated that because of limitations in amino acids supplied from microbial and ruminal escape protein in young growing cattle, amino acid supply may limit the magnitude of N retention response to bST under many situations. PMID- 1640267 TI - Chronic food restriction amplifies the effect of lactation on the duration of postpartum anestrus in rats. AB - We studied the effects of food intake and lactation on the duration of postpartum infecundability in rats. Sprague-Dawley rats were given free access to a purified diet (AIN-76A) or a similar diet (modified to contain twice the concentrations of vitamins and minerals) in amounts equal to 50% of that consumed by controls. At 65 d of age, animals were bred. At parturition, dams were allowed to nurse 4-5 pups, or all pups were removed. Thus, four groups were created: lactating control (n = 11), nonlactating control (n = 11), lactating food restricted (n = 8), and nonlactating food restricted (n = 10). Vaginal cytology was observed twice daily for the detection of proestrus, which occurred at 4.5 +/- 0.5 and 6.7 +/- 0.5 d (mean +/- SD) postpartum in nonlactating control and food restricted groups, respectively (P less than 0.005), and at 16.5 +/- 0.5 and 28.8 +/- 0.5 d postpartum in lactating control and food restricted groups, respectively (P less than 0.0001). The interaction between food intake and lactation was significant (P less than 0.0001). These results indicate that maternal food restriction exacerbates the effects of lactation in prolonging postpartum anestrus. PMID- 1640268 TI - Dietary fish protein modulates high density lipoprotein cholesterol and lipoprotein lipase activity in rabbits. AB - To explore the pathways by which fish protein feeding influences HDL metabolism, postheparin plasma lipoprotein lipase and hepatic triglyceride lipase activities were measured in rabbits fed fish protein or soybean protein combined with corn oil or coconut oil in a 2 x 2 factorial arrangement. In addition to greater serum total and LDL-cholesterol concentrations, the elevated HDL cholesterol concentration caused by feeding fish protein, compared with soybean protein, was accompanied by lower VLDL triglycerides and parallel higher lipoprotein lipase activity in fish protein-fed rabbits. These results suggest an enhanced assembly of circulating HDL through promoted lipoprotein lipase activity in rabbits fed fish protein. Moreover, dietary proteins and lipids interacted with one another to alter HDL triglycerides and liver cholesterol concentrations. Diet-induced changes in lipoprotein lipase activity were, however, not related to insulinemia, which was unaltered by purified diet feeding. The present results suggest that fish protein may affect HDL metabolism through the modulation of lipoprotein lipase activity in rabbits. PMID- 1640269 TI - Prolonged acetaminophen ingestion by mice fed a methionine-limited diet does not affect iron-induced liver lipid peroxidation or S-adenosylmethionine. AB - This study determined whether acetaminophen (ACAP)-induced glutathione depletion was associated with liver lipid peroxide formation, or the concentrations of liver S-adenosylmethionine and S-adenosylhomocysteine in mice fed diets with L methionine below or at the requirement level (0.25 or 0.5%) for 7 wk. Iron dextran (281 mg/kg body wt) or saline was administered for 2 d before measurement of lipid peroxide formation. Chronic dietary ACAP (0.5%) in mice fed 0.25% methionine caused a failure to maintain body weight even though food intake was similar to intake by all other treatment groups. Liver GSH (measured as nonprotein sulfhydryl concentration) and cysteine concentrations were depleted by ACAP and by ACAP plus iron. Liver lipid peroxide formation was increased by iron but was not altered additionally by ACAP ingestion. Liver glutathione peroxidase activity was increased by methionine in controls, whereas glutathione S transferase activity was increased by ACAP ingestion in mice fed 0.5% methionine compared with controls. Liver S-adenosylmethionine and nuclear 5 methyldeoxycytidine concentrations were not affected by dietary ACAP or methionine. Liver S-adenosylhomocysteine levels were lower in mice fed ACAP and 0.25% methionine compared with mice fed ACAP and 0.5% methionine. In conclusion, chronic ACAP did not increase the susceptibility of mice to liver lipid peroxidation or alter the availability of methyl groups for methylation reactions. PMID- 1640270 TI - Inanition may reduce alkaline phosphatase activity in liver and intestine of zinc deficient mice. AB - Zinc-deficiency was induced in mice by feeding a Zn-deficient basal diet (ZD dietary group) containing 9% lipid (6% corn oil, 3% cod liver oil) for 8 wk. Thereafter, the corn oil was withdrawn from the basal diet and a subset of Zn deficient animals (ZDLR group) was fed this modified low fat diet for another 8 wk. Alkaline phosphatase activity in intestine and liver was compared in these mice and in those allowed ad libitum access to the lipid-adequate Zn-supplemented diet (ZS group), in those pair-fed the Zn-supplemented diet (PF group) and in those fed the lipid-adequate, Zn-deficient diet ad libitum (ZD group). The enzyme activity in both intestine and liver of the ZDLR group was greater than in those of the ZD group and greater than or equal to those of the ZS and PF diet groups. The results of this study suggest that the reduction in alkaline phosphatase in Zn-deficient animals is a response secondary to associated inanition. PMID- 1640271 TI - (n-3) fatty acids, tissue lipid peroxidation and tocopherol status. PMID- 1640272 TI - Success: yours, mine, and ours. PMID- 1640273 TI - Nursing diagnoses as guidelines in the care of the neonatal ECMO patient. AB - The number of centers offering extracorporeal membrane oxygenation (ECMO) as a treatment for neonatal respiratory failure continues to grow. To ensure high quality patient care and consistency among centers, nursing care guidelines should be established. A plan of care using nursing diagnoses as guidelines for the ECMO nurse is presented. PMID- 1640274 TI - Pulmonary edema in pregnancy. AB - Normal cardiovascular and respiratory changes in pregnancy can predispose women to the development of pulmonary edema. Conditions and treatments unique to pregnancy, such as multiple gestation or tocolysis, further increase this risk. Recognition of risk factors and signs and symptoms of pulmonary edema allows the nurse to intervene quickly, thus decreasing potential complications to the mother and child. PMID- 1640275 TI - Nursing care of the neonate receiving high-frequency jet ventilation. AB - Respiratory distress remains a major source of morbidity and mortality among infants, despite advances in conventional mechanical ventilation over the past 20 years. High-frequency jet ventilation provides an alternative treatment modality for neonates suffering from pulmonary air leak syndromes, such as pulmonary interstitial emphysema and pneumothorax. This new technology presents special challenges to the nurse caring for these critically ill neonates and their families. PMID- 1640276 TI - Understanding bulimia and its implications in pregnancy. AB - Bulimia is a serious eating disorder that affects up to 19% of women in the United States. Research shows that bulimia may present a threat to the normal course of pregnancy. Nursing can play an important role in the prevention of maternal and neonatal morbidity through the early detection of bulimia. Bulimia and its impact on pregnancy are described to assist nurses in the early detection and referral of women with this disorder. PMID- 1640277 TI - Syphilis. An old disease, a contemporary perinatal problem. AB - The incidence of syphilis in the United States has almost doubled in the past 5 years, with some cities posting an increase of more than 500% during this period. As a result, greater numbers of neonates infected with congenital syphilis are treated in nurseries across the country. The incidence, pathogenesis, diagnosis, and treatment of syphilis are described, and the nursing implications associated with caring for those at risk of contracting the disease are presented. PMID- 1640278 TI - Efficacy of heparin in peripheral venous infusion in neonates. AB - OBJECTIVE: To determine the efficacy of continuous, low-dose heparin infusion in prolonging peripheral venous catheter patency in neonates. DESIGN: Randomized, prospective study. SETTING: Level III neonatal intensive-care unit. PARTICIPANTS: 113 neonates requiring i.v. therapy. INTERVENTIONS: The neonates were randomly assigned to heparin (n = 63). The heparin group received 1/2 unit of heparin per milliliter of continuous intravenous infusate or intermittent heparin flush. MAIN OUTCOME MEASURES: Low-dose heparin infusion does not make a difference in the duration of peripheral venous catheter patency. The incidence of catheter-related complications in the heparin group is the same as for those receiving no heparin. RESULTS: The mean duration of catheter patency was 62.75 hours in the heparin group and 27.3 hours in the no-heparin group (p = .0001). The occurrence of infection, bleeding, and extravasation injury was zero in the sample studied. The incidence of phlebitis was 18 cases in 132 (13%) in the heparin group and 13 cases in 122 (10%) in the no-heparin group. According to chi-square analysis, the difference between groups was not statistically significant (p greater than .05). CONCLUSION: Low-dose heparin infusion in peripheral venous catheters in neonates increased the duration of intravenous catheter patency (p = .0001) without increased risks of bleeding, infection, phlebitis, or extravasation injury. PMID- 1640280 TI - Second-trimester termination. PMID- 1640279 TI - Second-trimester termination. PMID- 1640281 TI - Clinical application of ultrasonography in the diagnosis of intussusception. AB - Sixty-five consecutive patients seen in a pediatric emergency department, in whom the diagnosis of intussusception was considered, had an ultrasound examination of the abdomen before a barium enema. The mean age of the patients was 1.7 years (range 2 weeks to 5 years). Intussusception was detected by ultrasonography in all 20 cases proved by barium enema. There were three false-positive ultrasound results (sensitivity = 100%, confidence interval (Cl) = 86% to 100%; specificity = 93%, Cl = 86% to 96%). Normal findings on ultrasonography correlated with a negative barium enema results in 42 of 42 cases (negative predictive value = 100%, Cl = 94% to 100%). No intussusception was missed by ultrasonography. To determine which patients would most benefit from ultrasonography, we divided patients into either a high-risk group (81% with intussusception) or a low-risk group (14% with intussusception) on the basis of clinical symptoms (p less than 0.01). If each high-risk child had a barium enema and each low-risk child had an ultrasound study as their initial diagnostic test, 89% of the patients in this study would have undergone only one examination. We conclude that ultrasonography can be used as a rapid, sensitive screening procedure in the diagnosis or exclusion of childhood intussusception. Children considered at low risk of having intussusception on the basis of clinical symptoms should initially have an ultrasound examination; patients at high risk should have an immediate barium enema. PMID- 1640282 TI - Differences in the immunogenicity of three Haemophilus influenzae type b conjugate vaccines in infants. AB - OBJECTIVE: To compare the immunogenicity of three Haemophilus influenzae type b (Hib) conjugate vaccines in infants residing in different geographic areas. DESIGN: A multicenter, randomized immunogenicity trial with sera assayed in one laboratory without knowledge of vaccine brand status. In Minneapolis and Dallas, infants were vaccinated at 2, 4, and 6 months of age; in St. Louis, infants were vaccinated at 2 and 4 months of age. SUBJECTS: A convenience sample of 458 infants recruited largely from private pediatric practices. MEASUREMENTS AND RESULTS: At each of the study sites, the respective trends between the anticapsular antibody responses of the infants assigned to the different conjugate vaccine groups were similar. After one or two doses, Hib polysaccharide conjugated to outer membrane protein complex of Neisseria meningitidis (PRP-OMP) was more immunogenic than Hib polysaccharide-tetanus toxoid conjugate (PRP-T), or Hib oligomers conjugated to the mutant diphtheria toxin CRM197 (HbOC) (p less than 0.001). After two doses, PRP-T was more immunogenic than HbOC (p less than or equal to 0.001). After three doses there was no significant difference in the geometric mean antibody concentrations of the three groups, and 88% to 97% of the infants had greater than 1.0 microgram/ml of antibody. The HbOC vaccine elicited a 10-fold lower antibody response after two doses (0.45 micrograms/ml vs 5.9 micrograms/ml) and a threefold lower antibody response after three doses (6.3 micrograms/ml vs 22.9 micrograms/ml) than observed by us previously with a prelicensure lot of this vaccine (p less than 0.001). Because of these low responses, the infants in St. Louis who received two doses of HbOC were revaccinated with unconjugated PRP at a mean age of 8.9 months. This group was immunologically primed, as evidenced by a 10-fold increase in geometric mean antibody concentration after vaccination at an age when unprimed infants do not normally respond to this vaccine. CONCLUSIONS: In infants in three geographic regions, PRP-OMP elicited earlier acquisition of serum antibody than the other two conjugate vaccines; however, after three doses the antibody concentrations of the three groups were not significantly different. The reason for the markedly lower immunogenicity of HbOC vaccine than reported previously is unknown. PMID- 1640283 TI - Mycobacterium haemophilum causing perihilar or cervical lymphadenitis in healthy children. AB - We describe five apparently immunologically normal children with infection caused by Mycobacterium haemophilum and resulting in perihilar or cervical lymphadenitis. Clinical distinction from Mycobacterium tuberculosis infection could be made by culture only, because differential Mantoux test results suggested tuberculosis. Treatment of these children involved chemotherapy or surgery or both, and outcome in all cases has been excellent. We believe that M. haemophilum should be added to the list of non-tuberculosis mycobacteria known to cause lymphadenitis in otherwise healthy children. PMID- 1640284 TI - Inappropriate suppression of thyrotropin during medical treatment of Graves disease in childhood. AB - Twenty-nine patients (22 female) aged 2 to 17 years were followed with serial measurements of serum triiodothyronine, thyroxine, and thyrotropin during medical therapy for Graves disease. Fourteen patients had 17 instances of hypothalamic pituitary-thyroid suppression with inappropriately low thyrotropin levels. Five patients had six episodes of low thyroxine and triiodothyronine levels with normal levels of thyrotropin, and 10 patients had 11 episodes of normal thyroxine and triiodothyronine levels with subnormal levels of thyrotropin. We conclude that thyrotropin values may not be reliable for diagnosing either mild hypothyroidism or persistent hyperthyroidism during the medical treatment of Graves disease. PMID- 1640285 TI - Growth and thyroid function in children treated with growth hormone. AB - We examined the effect of growth hormone (GH) therapy on thyroid function in 57 children with isolated GH deficiency and whether this effect could influence their growth response. Thyroid function and insulin-like growth factor I levels were measured before and after 3, 6, and 12 months of recombinant-GH therapy (20 U/m2 per week, given subcutaneously), after a 1-month withdrawal from therapy, and after a further 6 months of GH administration. The serum concentration of triiodothyronine (T3) and the T3/T4 (thyroxine) ratio increased after 12 months of GH treatment, whereas total T4 and free T4 levels decreased; thyrotropin levels did not change significantly during treatment but increased after a 1 month withdrawal. After a further 6 months of GH therapy, an increase in T3 levels and in the T3/T4 ratio and a decrease in total T4 and free T4 levels were found again, and thyrotropin levels decreased. The increment in growth velocity after 12 months of therapy correlated positively with the T3/T4 ratio and negatively with total T4 and free T4 values. These data confirm in children a GH induced enhancement of peripheral conversion of T4 to T3. This effect appears to be more evident in children who are most sensitive to GH in terms of growth promoting activity. PMID- 1640286 TI - Nocturnal thyrotropin surge in growth hormone-deficient children. AB - Because some patients with growth hormone (GH) deficiency are found to be hypothyroid after initiation of treatment with GH, we assessed the predictive value of the nocturnal thyrotropin surge (a sensitive test for central hypothyroidism) in 56 untreated GH-deficient children and adolescents. Eighteen patients had a subnormal thyrotropin surge (mean 18% (range -30% to 46%)), significantly less than that of 96 normal control subjects (mean 124%; 95% confidence limits, 47% to 300%; p less than 0.01); 13 of the 18 had a subnormal total thyroxine (T4) level or a subnormal free T4 level, or both. These 18 patients were given thyroid hormone replacement therapy; GH deficiency was confirmed during treatment with thyroxine. Of the remaining 38 patients, who had no initial evidence of dysfunction of the hypothalamic-pituitary-thyroid axis, 23 were re-examined while they were receiving GH treatment. Hypothyroidism developed in none of those 23 children during GH therapy. The nocturnal thyrotropin surge test and determination of iodothyronine levels were repeated in 14 of these euthyroid patients. There was no significant change in mean thyrotropin surge (129% (range +49% to +300) vs 125% (range +51% to +222%)), mean serum level of total T4 (111 +/- 4 vs 103 +/- 3 nmol/L), mean serum level of free T4 (19 +/- 0.7 vs 18 +/- 0.8 pmol/L), mean serum level of triiodothyronine (2.5 +/- 0.1 vs 2.5 +/- 0.1 nmol/L), or mean serum level of thyrotropin (2.9 +/- 0.3 vs 2.9 +/- 0.5 mU/L (mean +/- SEM)). We conclude that GH treatment does not appreciably alter thyroid function in GH-deficient patients who have no evidence of thyroid axis dysfunction before GH treatment. PMID- 1640287 TI - Maximal voluntary work and cardiorespiratory fitness in patients who have had Kawasaki syndrome. AB - To assess the natural history of Kawasaki syndrome and its effect on maximal voluntary work and cardiorespiratory fitness, we performed cycle ergometry testing in 47 patients who had had the syndrome. Forty-one patients performed maximal effort as judged by achievement of 95% predicted heart rate response. Oxygen consumption, carbon dioxide production, and minute ventilation were performed in 23 patients. There was no difference in maximal voluntary work (total work, mean power) or maximal oxygen consumption between case subjects and control subjects. There were no differences between patients with and those without aneurysms. Serial exercise studies were performed in 10 patients; of these, two with initially normal exercise study findings had decreased maximal voluntary work and oxygen consumption with ischemic changes, and both were at high risk for the development of stenotic or occlusive coronary arteries. The other eight patients had normal cardiorespiratory reserve and no ischemic changes with serial studies. These results suggest that patients have normal cardiorespiratory fitness after Kawasaki syndrome. With the development of ischemic heart disease, they may have decreased cardiorespiratory reserve. Serial evaluation of cardiorespiratory fitness may demonstrate ischemic heart disease. PMID- 1640288 TI - Oxygen desaturation during sleep in infants and young children with congenital heart disease. AB - Oxygen saturation (SaO2) during sleep and pulmonary functions were evaluated in 19 infants with congenital heart disease, aged 6 +/- 4 months, and in 11 normal infants, aged 8 +/- 5 months, to determine whether infants with congenital heart disease have more frequent oxygen desaturation during sleep and, if so, its relationship to underlying pulmonary function. Infants with congenital heart disease were classified as acyanotic (n = 11) or cyanotic (n = 8) on the basis of their aortic SaO2 at the time of cardiac catheterization (greater or less than 90% SaO2). Pulmonary function tests included respiratory rate, functional residual capacity, total respiratory system compliance, and maximal flows at functional residual capacity. Significant differences were found in the values for the lowest SaO2 of each 5-minute epoch (SaO2L) averaged during the entire sleep time (normal 94% +/- 2%, acyanotic 90% +/- 3%, and cyanotic 74% +/- 4%; p less than 0.01). The three groups also differed significantly in frequency distributions of percentage of total sleep time with SaO2L less than 90% (SaO2%T) (normal 10% +/- 17%, acyanotic 36% +/- 34%, and cyanotic 97% +/- 4%; p less than 0.05). Compared with the control group, the acyanotic group had a higher respiratory rate (66 +/- 19 breaths/min vs 35 +/- 6 breaths/min; p less than 0.01), a lower tidal volume (65% +/- 29% predicted vs 105% +/- 18% predicted; p less than 0.01), and a lower total respiratory compliance (59% +/- 18% predicted vs 106% +/- 30% predicted; p less than 0.01). A negative correlation existed between SaO2%T and aortic SaO2 (R2 = 0.64; p less than 0.01). We conclude that oxygen desaturation occurs during sleep in infants with congenital heart disease; the presence of desaturation appears to be related to the initial degree of hypoxemia and the presence of abnormal pulmonary function. PMID- 1640289 TI - Primary distal tubular acidosis in childhood: clinical study and long-term follow up of 28 patients. AB - The long-term follow-up of 28 patients with congenital primary tubular acidosis is described. Ten patients had affected siblings but no history of similar symptoms in the preceding generation. Deafness was associated in 14 patients and developed before 12 years of age. Deafness was present in all familial cases, and patients without deafness showed no familial incidence, suggesting the existence of two different entities. All patients had growth retardation, which was more severe in the older patients and was always markedly improved by alkaline therapy. Rickets was found in some patients but seemed related to vitamin D deficiency. Catch-up growth was limited to the first 2 years of therapy in patients treated before 2 years of age, but sometimes lasted longer in older patients. Of the 12 patients who reached adulthood, those without rickets achieved a normal height but the others did not. We believe that therapy should be continued throughout life because of the risk of nephrocalcinosis. PMID- 1640290 TI - Sudden infant death syndrome in Washington State: why are Native American infants at greater risk than white infants? AB - Washington State reports one of the highest rates of sudden infant death syndrome (SIDS) in the United States; within the state, Native Americans have the highest rate of any racial group. To explore this apparent genetic predisposition, we conducted a population-based retrospective cohort study. Using the state's linked birth and death certificate file for 1984 to 1988, we compared infants whose mothers were coded as "American Indian" with infants whose mothers were coded as "white." Native American infants were more than three times more likely than white infants to die of SIDS (crude relative risk = 3.25; 95% confidence interval = 2.41 to 4.38). However, this elevated risk diminished after adjustment for differences between Native American and white mothers in age, marital status, parity, and smoking status during pregnancy (adjusted relative risk = 1.82; 95% confidence interval = 1.28 to 2.58). The high SIDS rate of Washington's Native Americans appears to be due to the high prevalence of SIDS risk factors among Native American mothers, rather than to a genetic predisposition in the infants. Because many of these maternal factors are related to socioeconomic status, it is likely that programs to improve the overall health of Native Americans might lessen both the impact of SIDS and that of other causes of infant morbidity and death. PMID- 1640291 TI - Immunoglobulin G, total and subclass, in children with or without recurrent otitis media. AB - Total IgG and subclasses IgG1, IgG2, IgG3, and IgG4 were measured in 89 subjects with recurrent otitis media. There was no significant difference between the groups with respect to the arithmetic or geometric mean levels for total IgG or subclasses IgG1, IgG2, IgG3, or IgG4. PMID- 1640292 TI - Iodine supplementation in children receiving long-term parenteral nutrition. AB - In 18 children receiving long-term total parenteral nutrition (TPN) without iodide supplements, thyroid function test results were normal but serum iodide levels were greater than in control subjects (p less than 0.01). Iodine contamination of TPN solutions and fat emulsions accounted for only half of the recommended parenteral intake. Skin absorption of topical iodinated disinfectant may explain the adequate, if not excessive, iodine intake. We conclude that iodine is an unnecessary supplement in TPN solutions. PMID- 1640293 TI - Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis. AB - We report an inborn error of the tricarboxylic acid cycle, alpha-ketoglutarate dehydrogenase deficiency, in three siblings with hypotonia, metabolic acidosis, and hyperlactatemia immediately after birth. Neurologic deterioration resulted in death at about 30 months of age. We propose low molar ratios of ketone bodies in plasma of neonates with congenital lactic acidosis as an indication of dysfunction of the tricarboxylic acid cycle. PMID- 1640294 TI - Plasma glutamine concentration: a guide in the management of urea cycle disorders. AB - Because increases in plasma glutamine concentrations are almost always associated with hyperammonemia in patients with urea cycle disorders, we determined the correlation between these two variables for 2 years in a child with ornithine transcarbamylase deficiency. A correlation coefficient of 0.77 (p less than 0.0001) was found. Hyperammonemia was rarely observed when plasma glutamine levels were near normal. These data suggest that one goal of therapy is the maintenance of plasma glutamine levels at or near normal values. PMID- 1640295 TI - Lactoferrin and lysozyme deficiency in airway secretions: association with the development of bronchopulmonary dysplasia. AB - To test whether the presence of airway inflammatory markers differentiated babies with hyaline membrane disease (HMD) who recovered (n = 18) from those in whom bronchopulmonary dysplasia (BPD) developed (n = 18), tracheal aspirate samples from 36 newborn infants with HMD who underwent intubation were collected during days 1 to 28 of life and analyzed for the mucosal antimicrobial proteins lactoferrin and lysozyme. For babies with HMD in whom BPD developed, lactoferrin concentrations were decreased during the first 4 days of life (7 +/- 3, 14 +/- 3, 18 +/- 3, and 18 +/- 3 micrograms/ml, respectively) in comparison with those in babies with HMD who recovered (23 +/- 8, 29 +/- 6, 41 +/- 9, and 81 +/- 19 micrograms/ml); group differences reached statistical significance on days 3 and 4 (p less than 0.05). Lysozyme levels in the secretions of babies with BPD were also lower on day 3 (31 +/- 5 micrograms/ml) than in those of babies who recovered (54 +/- 7.5 micrograms/ml). For babies with BPD whose endotracheal tube remained in place beyond day 4, lysozyme levels on days 5 to 12 were significantly lower for those classified as having severe BPD than for those with mild to moderate BPD. Because lysozyme and lactoferrin are products of serous cells found in submucous glands, it seems possible that the relative immaturity of submucous glands may influence the development of BPD. PMID- 1640296 TI - Phospholipid and surfactant protein A concentrations in tracheal aspirates from infants requiring extracorporeal membrane oxygenation. AB - To test the hypothesis that infants with severe respiratory failure and the need for extracorporeal membrane oxygenation (ECMO) are surfactant deficient, we measured the amount of surfactant phospholipids, disaturated phosphatidylcholine, surfactant protein A, and protein in tracheal aspirates from 22 infants, who received ECMO therapy for respiratory failure with meconium aspiration syndrome (n = 18) or pneumonia (n = 4). Tracheal suction material was obtained in a standardized way every 4 hours during the period of ECMO treatment and pooled for 24-hour periods. During ECMO, mean total phospholipid, disaturated phosphatidylcholine, and surfactant protein A values in tracheal aspirates increased and protein values decreased significantly, predominantly during the 72 hour period before infants were weaned from ECMO. Of the 22 infants, 14 had an increase in tracheal aspirate phospholipid values of more than 200% and were found to need a shorter period of ECMO support (p less than 0.005) and post-ECMO ventilatory support (p less than 0.025) than did the eight infants with stationary or only moderate increases in tracheal aspirate phospholipid values, three of whom had pneumonia. We conclude that infants with respiratory failure who require ECMO treatment often have surfactant deficiency. We speculate that surfactant treatment might decrease the need for or the duration of ECMO support. PMID- 1640298 TI - Effects of intraventricular hemorrhage and socioeconomic status on perceptual, cognitive, and neurologic status of low birth weight infants at 5 years of age. AB - A prospective longitudinal study assessed the effects of intraventricular hemorrhage (IVH) and socioeconomic status on the perceptual, cognitive, and neurologic status of preterm infants at 5 years of age. The preterm group consisted of infants with no IVH, grade I to II IVH, and grade III to IV IVH; a control group of normal term infants was also studied. Outcome was evaluated at 3, 4, and 5 years of age. Twenty-four percent of infants with grade III to IV IVH had abnormal neurologic diagnoses at 5 years of age. Correlations of predictor variables including IVH status, latency of visual evoked response, days of hospitalization, and socioeconomic status with 5-year neurologic outcome indicated that IVH status and visual evoked response at 1, 2, and 3 years continued to have an effect on neurologic outcome, but socioeconomic status and days of hospitalization did not; socioeconomic status did have a significant effect on the McCarthy cognitive scores but not on the perceptual scores at 5 years. Multiple regression analyses revealed that duration of hospitalization (reflecting neonatal morbidity), visual evoked response, and socioeconomic status all have independent effects on the cognitive index, whereas only duration of hospitalization has an independent effect on the perceptual index. These data support the concept that a complex interaction of biologic and environmental risk factors determines the degree of recovery from IVH by high-risk preterm infants. PMID- 1640297 TI - Hyperkalemia in very low birth weight infants. AB - PURPOSE: To assess the frequency and pathogenesis of hyperkalemia in the very low birth weight infant. METHODS: Infants who weighed less than 1000 gm at birth were prospectively entered into the study within 12 hours of birth. Potential risk factors for hyperkalemia were assessed. Body weight, fluid and electrolyte balance, serum levels of sodium and potassium, creatinine clearance, fractional sodium excretion, and urine sodium/potassium ratio were measured every 8 hours for 72 hours. Measurements of plasma renin, serum aldosterone, and plasma atrial natriuretic factor were made at study entry and repeated when hyperkalemia (serum potassium greater than 6.5 mmol/L) occurred or at 72 hours. Infants in whom hyperkalemia developed were compared with those in whom it did not. RESULTS: Thirty-one infants completed the study; hyperkalemia developed in 16 (51.6%). The only difference in the occurrence of perinatal complications was the more frequent occurrence of pH less than 7.20 in infants with subsequent development of hyperkalemia. Creatinine clearance, urine output, and potassium excretion were significantly lower in the hyperkalemia group during the first 24 hours. Serum potassium concentration at 24 hours was inversely related to urine output in the prior 24 hours. Fractional sodium excretion, urine sodium/potassium ratio, and levels of renin, aldosterone, and atrial natriuretic factor did not differ between groups. CONCLUSIONS: Hyperkalemia is a frequent complication in very low birth weight infants. Infants with low urinary flow rates during the first few hours after birth are at greatest risk for the development of hyperkalemia. PMID- 1640299 TI - Adherence of human newborn infants' monocytes to matrix-bound fibronectin. AB - The localization of monocytes to sites of inflammation is mediated by interactions with extracellular matrix components including fibronectin, a nonimmune opsonin with binding sites for collagen, fibrin, heparin, and cell surfaces. This study demonstrates that newborn infants' monocytes bind to both gelatin (i.e., denatured collagen) and matrix-bound fibronectin to a degree comparable to that of adult-derived cells. PMID- 1640300 TI - Persistent hypertension after prenatal cocaine exposure. AB - Multiple blood pressure readings were obtained with time in 12 infants with documented in utero exposure to cocaine. Approximately half had hypertension or high-normal blood pressure with no evidence of renal, cardiovascular, or endocrinologic abnormalities. PMID- 1640301 TI - Blood-brain barrier permeability in "healthy" infected and stressed neonates. AB - The assessment of the blood-brain barrier permeability (BBBP) showed that BBBP values were higher in stressed neonates and those with bacterial meningitis than in "healthy" infants or neonates with aseptic meningitis. The BBBP determination may be helpful in differentiating bacterial from aseptic meningitis; the high BBBP should be considered in the management of stressed neonates. PMID- 1640302 TI - Acute toxic reaction to carbamazepine: clinical effects and serum concentrations. AB - The clinical spectrum of toxic effects and serum concentrations after ingestion of carbamazepine were studied in 82 pediatric patients. Serum carbamazepine level was related to the depth of coma (p less than 0.001), convulsions (p = 0.002), hypotension (p less than 0.001), and the requirement for mechanical ventilation (p less than 0.001). In 10 patients in deep coma with a Glasgow Coma Scale (GCS) of 3-4, the mean serum level was 213 mumol/L (range 143 to 343); seizures, ventilatory failure, or hypotension caused by myocardial failure and conduction defects were observed. In four of these, large doses of inotropic agents were required, one patient was treated with plasmapheresis, and two died--one of cardiac failure and one of aspiration pneumonitis. In 27 patients with moderate coma (GCS 5-8), the mean serum level of carbamazepine was 112 mumol/L (range 63 to 176); convulsions were observed in two patients in this group. In 45 patients whose conscious state was mildly depressed or normal (GCS 9-15), the mean serum level was 73 mumol/L (range 37 to 128); additional effects were drowsiness (80%), ataxia (53%), nystagmus (38%), vomiting (17%), and dystonia (7%). I conclude that patients with serum carbamazepine levels of approximately 100 mumol/L require close observation, whereas those with levels greater than 150 mumol/L may require intensive life support. PMID- 1640303 TI - Randomized, controlled trial of antibiotic therapy for Escherichia coli O157:H7 enteritis. AB - We undertook a prospective, controlled study to evaluate the effect of trimethoprim-sulfamethoxazole in children with proven Escherichia coli O157:H7 enteritis on the duration fo symptoms, on fecal excretion of pathogen, and on the risk of progression to hemolytic-uremic syndrome. There was no statistically significant effect of treatment on progression of symptoms, fecal pathogen excretion, or the incidence of HUS (2/22 vs 4/25; p = 0.67). Our results suggest that a multicentric trial using rapid diagnostic methods to permit early randomization should be carried out. PMID- 1640304 TI - Use of ciprofloxacin in an infant with ventriculitis. AB - Ciprofloxacin was used successfully in a neonate with ventriculitis caused by a multiply resistant strain of Enterobacter cloacae. Limited pharmacokinetic data indicated that adequate concentrations of drug could be attained in cerebrospinal fluid. PMID- 1640305 TI - Hemodynamic responses to upright exercise of adolescent cardiac transplant recipients. AB - To characterize the hemodynamic response to exercise after cardiac transplantation, we asked seven adolescent transplant patients (aged 15.1 +/- 0.7 years; mean +/- SE) to perform upright discontinuous exercise to volitional exhaustion on a mechanically braked cycle ergometer. Data were compared with those of seven control subjects matched for age, gender, body mass, percentage of fat, and body surface area. The transplant group had lower peak power output values (92 +/- 13 vs 146 +/- 30 watts; p less than or equal to 0.001) and maximum oxygen consumption values (22 +/- 8 vs 32 +/- 8 ml/kg per minute; p less than or equal to 0.03), despite achieving the same peak venous lactic acid concentration (6.2 +/- 3 vs 5.9 +/- 3 mEq/L; p = not significant). The transplant group had a diminished heart rate in response to exercise--44% lower than the control group had (delta = 49 +/- 6.4 vs 87 +/- 9.1 beats/min; p = 0.005). The cardiac output response to exercise was maintained in the transplant group (delta = 6.5 +/- 1.5 vs 4.6 +/- 0.8 L/min; p = not significant) by an augmented stroke volume response (delta = 31 +/- 10 vs -4 +/- 3.4 ml; p = 0.01), which may relate to a greater decrease in systemic vascular resistance during exercise (delta = -13.7 +/- 2.2 vs -6.3 +/- 1.2 Wood units; p = 0.02). Thus adolescents who have undergone cardiac transplantation have a normal cardiac output response to upright exercise. This is accomplished, despite a blunted heart rate response, by an augmented stroke volume that may relate to the greater decrease in systemic resistance during exercise. PMID- 1640306 TI - Eleven-year-old girl with acute renal failure, arthritis, hyperuricemia, and family history of rheumatic disorders. PMID- 1640307 TI - Unforgettable patients. PMID- 1640308 TI - Breast-feeding and maternal-infant transmission of human immunodeficiency virus type 1. PMID- 1640309 TI - Use of alveolar-arterial gradient as predictor of outcome in respiratory failure. PMID- 1640310 TI - Use of alveolar-arterial gradient as predictor of outcome in respiratory failure. PMID- 1640311 TI - Breast-feeding and urinary tract infections. PMID- 1640312 TI - IgG4 deficiency and recurrent respiratory infections. PMID- 1640313 TI - Adjustment to chronic disease in relation to age and gender: mothers' and fathers' reports of their childrens' behavior. AB - Investigated age and gender differences in adjustment to chronic disease in children suffering from one of five conditions: diabetes, asthma, cardiac disease, epilepsy, and leukemia. Ratings of adjustment and disease-related restrictions were obtained separately from mothers and fathers. Factor analysis of the adjustment scale yielded 6 subscales which differentiated between children in terms of age and disease type, and to a lesser extent, gender. Mothers' and fathers' ratings of adjustment and restrictions were comparable, though fathers made less differentiation on the basis of disease or age. For both parents, perceived restrictions of the disease were associated with poorer adjustment in the child, and this was particularly reflected on indices of peer relations and work. PMID- 1640314 TI - Psychosocial adjustment in juvenile arthritis. AB - Psychosocial adjustment in 102 children with arthritis, ages 4-16, and their families was assessed by parents, who completed the Child Behavior Checklist (CBCL) and Profile of Mood States (POMS). On average, parental distress (POMS) was lower than reference norms. POMS distress was correlated with children's behavioral problems (r = .41) but not with children's social competence (r = .15). General linear models explained 25% of the variance in CBCL behavioral problem scores. Older age was associated with more behavior problems in males, but not females. Disease severity and disease activity were also associated with behavioral problems. Although 27% of the variance in CBCL social competence could be explained, no single predictor variable was especially strong. Poorer social competence was associated with older age and shorter disease duration. Teenagers, especially those with recent onset and those with mild disease activity, may be at increased risk for psychosocial maladjustment. PMID- 1640315 TI - Maternal depression, assessment methods, and physical symptoms affect estimates of depressive symptomatology among children with cancer. AB - Investigated the incidence of depressive symptoms and their covariates in a sample of 99 children undergoing treatment for cancer and their mothers. Although the prevalence of depressive symptoms falling within the clinical range was low (7 to 8%), classification of these children was highly dependent upon the informant and instrument used. Interrater reliabilities did not differ from chance levels. Separate multiple regression analyses of the mother's and nurse's ratings of the child's level of depression, the child's self-report on the Child Depression Inventory, and the mother's responses to the Child Behavior Checklist depression scales revealed different statistical models for each method of assessment. However, increased severity of the mother's self-report of depressive symptoms on the Beck Depression Inventory, which was predicted by low perceived social support and hospitalization of her child, was associated with higher levels of child depression on all child- and parent-report measures. Parental adjustment, sociodemographic, and medical factors as well as methods of assessment must be addressed by models explaining the etiology of depressive symptoms among pediatric oncology patients. PMID- 1640316 TI - Family resources and stress: a comparison of families of children with cystic fibrosis, diabetes, and mental retardation. AB - Assessed patterns of stress in families of children with pediatric conditions that varied on 2 dimensions: (a) fatal vs. nonfatal outcome and (b) presence vs. absence of cognitive impairment. Families of children with cystic fibrosis (n = 23), diabetes (n = 24), and moderate mental retardation (n = 24) were compared to families of well children (n = 24) in 3 age groups. Maternal responses to a multidimensional measure of family stress, the Questionnaire on Resources and Stress--Short Form (QRS-S), indicated that families of children with chronic conditions did not differ from families of well children on scales assessing generic aspects of family stress, such as family conflict. However, diagnostic groups differed on QRS-S scales assessing stressors specific to the child's disability (e.g., families of children with mental retardation were characterized by concerns about caring for the child as an adult). There was no evidence of higher levels of stress for families of older children. Data on the internal consistency of QRS-S scales and their relation to measures of maternal and child adjustment are presented. PMID- 1640317 TI - Measuring marital distress in couples with chronically ill children: the Dyadic Adjustment Scale. AB - The idea that couples with chronically ill children are particularly at risk for marital distress has been supported by clinical observation and empirical research. Three recent controlled studies, however, did not find evidence for this increased risk. A possible explanation for the discrepant findings is that these three studies employed Spanier's Dyadic Adjustment Scale (DAS) as a unidimensional measure of marital adjustment. To develop a better understanding of the discrepant findings of risk for marital distress in couples with chronically ill children, the present study examined both the appropriateness of the DAS's published norms as well as the criterion validity of the DAS for use in this population of couples. Three hundred and sixteen parents (158 couples) from a large urban pediatric health care setting completed a survey investigating interest and need to participate in an intervention program for marital distress. Results indicated that this instrument can reliably predict marital distress in this population of couples, however, mean DAS scores are higher than those established by Spanier. PMID- 1640318 TI - Emotional distress of mothers of hospitalized children. AB - Compared 20 mothers of children hospitalized on a pediatric intensive care unit (PICU), 20 mothers of children hospitalized on a general pediatric medical surgical unit, and 20 mothers of nonhospitalized ill children on standardized measures of anxiety and negative moods. The mothers of children admitted to the PICU experienced greater state anxiety, depression, confusion, and anger than the other mothers. There were no differences between the mothers of children admitted to the general pediatric floor and mothers of nonhospitalized ill children. Maternal age, family stress, number of prior hospitalizations of the ill child, and the mother's rating of the severity of her child's illness were predictive of emotional distress. Results indicate that hospitalization of a mildly or moderately ill child per se may not necessarily increase maternal emotional distress. PMID- 1640319 TI - Fetal intestinal transplantation: a new therapeutic approach in short-bowel syndrome. AB - Intraperitoneally transplanted fetal rat intestine can be anastomosed to the intestine of the host after 4 weeks of maturation. In syngeneic transplant combinations morphological findings as well as functional parameters suggest that the intestinal transplant might provide a substitute for normal intestinal tissue. Four weeks after fetal intestinal transplantation in adult Lewis rats we resected the total small bowel of the host and interposed the matured transplant. Resection of total small bowel without transplant interposition led to a decline of body weight in control animals but was prevented in the transplanted group. After total small bowel resection and cecectomy (a lethal resection in the control group) we found a 40% (4/10) survival in the group in which the transplant had been anastomosed to the remaining bowel. PMID- 1640320 TI - The effect of surgical trauma on the bacterial translocation from the gut. AB - Bacterial translocation is the passage of viable bacteria from the lumen of the gastrointestinal tract through the intestinal mucosa to other sites. It is believed that bacterial translocation may lead to infection and septicemia. The purpose of this study was to determine what factors in experimental surgical trauma lead to bacterial translocation. Two-month-old Wistar albino rats were divided into five groups: (A) control; (B) anesthesia (ether inhalation); (C) anesthesia and surgery (median laparotomy and transient compression of the intestines); (D) fasting only; and (E) anesthesia, surgery, and fasting. After 48 hours, ileum, mesenteric lymph nodes, and blood were cultured for aerobic and anaerobic organisms. In each group the number of animals with bacteria overgrowth was calculated. The incidence of bacterial translocation to mesenteric lymph nodes and blood in groups B and D were similar to the controls (P greater than .01). There was a significant increase in the number of animals with bacterial translocation in groups C and E (P less than .001). The majority of translocating bacteria were E coli. PMID- 1640321 TI - Indomethacin administration after temporary ischemia causes bowel necrosis in mice. AB - Several reports have suggested indomethacin administration causes necrotizing enterocolitis (NEC) in infants. Few experimental studies have addressed this relationship. We studied the effects of indomethacin after temporary intestinal ischemia in CD-1 mice, using a previously reported method of simulating NEC in mice. This involved occlusion of both superior mesenteric vessels for 15 minutes. Three groups were studied. In group 1, 12 mice had superior mesenteric vessels occluded for 15 minutes, followed by intravenous (IV) administration of saline for three doses over 3 days. In group 2, 12 mice had sham laparotomy, without occlusion of vessels, followed by IV administration of indomethacin for three doses over 3 days. In group 3, 36 mice had mesenteric vessel occlusion for 15 minutes, followed by IV administration of indomethacin for three doses over 3 days. The results were as follows: group 1, bowel necrosis developed in 1 of 12 animals (8%); group 2, all 12 animals survived without bowel damage (0%); and group 3, 22 of 36 animals developed bowel necrosis (61%) (Fisher's Exact Test: occlusion alone v occlusion and indomethacin, P = .002; indomethacin alone v occlusion and indomethacin, P = .00015.) We conclude that whereas occlusion alone or indomethacin alone does not cause bowel necrosis, temporary intestinal occlusion followed by indomethacin causes bowel necrosis in over 60% of animals studied. In the shocked preterm infant who may have suffered temporary intestinal ischemia, administration of indomethacin may be the second step to development of NEC. PMID- 1640322 TI - Intravascular haemolysis in association with necrotising enterocolitis. AB - Severe haemolysis is an unusual occurrence in association with necrotising enterocolitis (NEC). Activation of the Thomsen-Friedenreich (T) antigen on the neonatal erythrocytes is proposed as the mechanism. This haemolytic process is precipitated by transfusion with serum-containing blood products, which should therefore be avoided. Once haemolysis has become established the outcome is usually fatal. This report describes the management of four neonates who had established haemolysis complicating severe NEC. T activation was confirmed in two infants, but could not be tested for in the other two. Exchange transfusion abolished the haemolysis in two patients, who survived. Despite reduced use of blood products the other two infants died. We believe that exchange transfusion was essential in the successful management of the infants who survived, and recommend early exchange transfusion when haemolysis complicates NEC. PMID- 1640323 TI - Differences in phosphorylation state of neurofilament proteins in ganglionic and aganglionic bowel segments of children with Hirschsprung's disease. AB - Hirschsprung's disease is characterized by the absence of enteric neurons in the myenteric and submucosal plexus and the presence of many unmyelinated axons, visible in ganglion like structures, in the aganglionic part of the bowel. In previous studies we showed that the immunoreactivity of a monoclonal antibody (2F11) specific for neurofilament proteins is increased in aganglionic bowel segments. We now investigated whether the increased neurofilament protein staining results from an increase in neurofilament protein immunoreactivity in the aganglionic segment or if it is also related to differences in the phosphorylation state of neurofilament proteins. Bowel resection specimens of patients with Hirschsprung's disease and control patients were investigated by immunohistochemical techniques using a panel of different monoclonal antibodies that are specific for neurofilament proteins and have well known reaction patterns against different phosphorylated epitopes present on two neurofilament proteins, the middle (NF-M) and the high (NF-H) molecular weight subunit. For comparison the specimens were also stained for acetylcholinesterase, neuron specific enolase (NSE), S-100, and glial fibrillary acidic protein (GFAP). Immunostaining with this panel of antineurofilament-antibodies showed differences in the phosphorylation state of neurofilament proteins in the aganglionic and the ganglionic bowel segments of patients with Hirschsprung's disease. These changes involved the phosphorylation state of these proteins and the ratio of NF-H and NF M in neurofilament proteins. Staining with NSE and S-100 showed no significant differences between Hirschsprung's disease patients and control patients. We surmise that during the ingrowth and differentiation of hypertrophic axons the composition of neurofilament proteins formed in the aganglionic bowel segment differs from the neurofilament proteins formed in the ganglionic and control bowel segments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640324 TI - Hirschsprung's disease: diagnosis using monoclonal antibody 171B5. AB - A new reliable immunohistochemical method for diagnosing Hirschsprung's disease (HD) using our unique monoclonal antibody (MAb) 171B5 against synaptic vesicles is described. Fresh frozen sections of rectal tissues were used from 13 patients with HD aged 2 weeks to 13 months; 9 had rectosigmoid HD and 4 had total colonic aganglionosis (TCA). Comparable normal colonic and rectal specimens were also obtained from 13 age-matched controls. All specimens were labeled with MAb 171B5, to demonstrate neuronal innervation patterns of both mucosa and submucosa. In all control specimens, many synapses arranged in variciform plexuses were seen in the lamina propria, a moderate number in the muscularis mucosae, and dense clusters in the submucosal plexus. In all aganglionic specimens, only scanty numbers of synapses which were not organized in variciform plexuses were seen in the lamina propria, none in the muscularis mucosae, and a few in the submucosa. These findings suggest that MAb 171B5 immunohistochemistry on the lamina propria alone can differentiate between normal and aganglionic bowel and appears to be a reliable and useful method for detecting HD on suction rectal biopsy. PMID- 1640325 TI - Mucosal neuroendocrine cell abnormalities in the colon of patients with Hirschsprung's disease. AB - We studied the distribution of mucosal neuroendocrine (NE) cells in the colon from 13 patients with Hirschsprung's disease (HD) and from 8 controls. Immunohistochemical studies were carried out using monoclonal and polyclonal antibodies against chromogranin A and synaptophysin (general markers of NE cells), 5-hydroxytryptamine (5-HT) (a marker of amine), peptide YY (PYY), and somatostatin (markers of neuropeptides). Chromogranin A immunoreactive cells were significantly increased in the aganglionic bowel compared with ganglionic bowel and controls (P less than .05). There was an increase in the number of synaptophysin immunoreactive cells in the aganglionic bowel compared with ganglionic bowel and controls but the results were not statistically significant. 5-HT immunoreactive cells were also significantly increased in the aganglionic bowel compared with ganglionic bowel and controls (P less than .05). The immunostaining for PYY demonstrated abundance of this NE cell type in the aganglionic bowel and this was highly significant compared with ganglionic bowel and controls (P less than .001). There was a significant increase in somatostatin immunoreactive cells in the aganglionic bowel compared with ganglionic bowel (P less than .01). The increase in neuroendocrine cells was found over the entire length of the aganglionic segment in rectosigmoid HD as well as in long-segment HD. These results demonstrating the increased levels of NE cells in the mucosa of aganglionic colon suggest that the NE cells may have a role in regulating the sustained contraction of the aganglionic intestine in HD. PMID- 1640326 TI - A study of mucosal gut immunity in infants who develop Hirschsprung's-associated enterocolitis. AB - The aim of this study was twofold. First, to establish quantitatively the distribution of the immunoglobulin-containing (plasma) cells, T and B lymphocytes in the lamina propria of the rectal mucosa of normal neonates and neonates with Hirschsprung's disease (HD). Second, to review the neonates with HD to determine any differences in these cell populations between those who subsequently developed Hirschsprung's enterocolitis (HEC) and those who did not. Two conclusions can be drawn from the results of our study of rectal mucosal immune defenses. First, neonates with HD have no deficiencies in these defenses when compared with normal neonates. Second, neonates with HD who subsequently develop HEC have no premorbid deficiency in these defenses. It was noted that the pan-T cell count in the infants who went on to develop HEC appeared to be increased, although this did not reach statistical significance. The use of fresh or frozen material would permit a more detailed analysis of the separate T cell subsets. PMID- 1640327 TI - Paediatric liver transplantation: life after portoenterostomy in biliary atresia. AB - Seventy-five percent to 80% of patients with biliary atresia (BA) will be candidates for paediatric liver transplantation (PLTx) throughout the first 14 years of life. They form the main group of recipients in our Paediatric Liver Transplant Unit. Of 48 children transplanted, 21 (44%) had BA. These patients present particular features, average weight of 12 kg, mean age of 3 years, and severe malnutrition prior to PLTx, which distinguish them from other paediatric candidates. With the advent of PLTx, portoenterostomy (PE) has ceased to be the only recourse for treating the majority of patients with BA. Different factors converge in these patients: some, including haemorrhage and adhesions, may present technical difficulties, and others, such as infections (19% in this series) due to severe malnutrition and malabsorption and consequent chronic rejection (14% in this series), often lead to death in the postoperative period (33% in this series). BA is treated by all paediatric surgeons, but the overall success rate now depends not only on PE but also on PLTx. In an attempt to facilitate possible later PLTx in pts with BA, the authors as paediatric surgeons performing PE or PLTx present surgical modifications and emphasize the most important medical aspects conducive to the improved general status of these pts. Our aim was to establish guidelines for taking full advantage of PE while preventing posterior problems and facilitating future transplant surgery. PMID- 1640328 TI - Symptomatic hemorrhoids and anorectal varices in children with portal hypertension. AB - There have been few reports of the anorectal problems encountered in children with portal hypertension. We report the incidence of anorectal symptoms in a retrospective study of 189 children treated by injection sclerotherapy for esophageal varices secondary to portal hypertension. Anorectal symptoms, proctoscopic findings and treatment have been recorded in this group. The incidence of symptomatic hemorrhoids and rectal varices was 4.2%. Hemorrhoids are rare in children and the increased incidence can be assumed to be secondary to portal hypertension. Treatment is advised only for symptomatic patients and injection sclerotherapy is satisfactory for the majority. PMID- 1640329 TI - A prospective analysis of vascular access device-related infections in children. AB - To identify significant predictors of device-related infections, we performed a prospective, nonrandomized analysis of our experience with vascular access devices over a 2-year period in a pediatric oncology population. Variables analyzed included: (1) age at placement, (2) sex, (3) underlying disease, (4) type of device used (catheter v port), and (5) total white blood cell count at placement. Quantitative microbiologic criteria were used for diagnosis of bacteremia while clinical and microbiologic criteria were used in diagnosis of tunnel/port/site infections. During the study period a total of 351 devices, comprising 78,159 days in situ, were placed and data for univariate and multivariate analysis were available on 271 (77%). The mean age at placement was 7.2 +/- 4.7 years for catheters and 9.5 +/- 4.8 years for implantable devices (P less than or equal to .01). Significant predictors of device-related infections in univariate analysis were type of device (P less than or equal to .0001) and age (P less than or equal to .002). External catheters and age less than or equal to 7 years were associated with increased risk of infection. Underlying disease had a marginal effect on the infection rate (P = .08). In multivariate analysis, device type (P less than or equal to .0001) and age (P less than or equal to .002) continued to affect infections, whereas underlying disease demonstrated only a borderline effect (P = .14). We conclude that device type and age significantly affect the rate of device-related infections. These data support increased use of implantable devices in pediatric oncology patients. PMID- 1640330 TI - Experimental reovirus type 3-induced murine biliary tract disease. AB - The aims of this experiment were: (1) to establish a reovirus type 3-induced murine model of biliary atresia/neonatal hepatitis that as far as possible corresponds to the human disease; (2) to demonstrate that the disease is histologically similar to the human disease, and to investigate the natural history of reovirus type 3 infection in this model; (3) to study the host-virus interrelationships at a molecular level; and (4) to develop sensitive assays that could be translated to the human disease. In this study we were unable to produce an exact model for extrahepatic biliary atresia (EHBA) in the laboratory mouse following a perinatal reovirus type 3 infection. However, the ability of reovirus type 3 to persist in the murine liver and the effects produced in the offspring of infected pregnant mice indicate that this preparation may provide the basis for the eventual development of the experimental model of EHBA. PMID- 1640331 TI - Predicting preoperatively the outcome of respiratory symptoms of gastroesophageal reflux. AB - The fact that bronchopulmonary symptoms remain unchanged in about 15% of patients after successful operation for gastroesophageal reflux (GER) with respiratory tract disease (RTD) makes surgical indications uncertain and warrants further research into preoperative prognostic predictors. This problem has been addressed in infants by demonstrating that those most likely to be cured by antireflux procedures have long nocturnal episodes of GER and/or temporal coincidence between drops in pH levels and respiratory episodes. In an attempt to validate these predictors and, at the same time, to search for other reliable ones, we have retrospectively studied the charts, manometric studies, pH tracings, and pathology reports of 55 patients aged 48 +/- 36 months (range, 2 to 170) who had Nissen funduplication for GER with RTD in the last 10 years. Forty-five children were cured or improved of their RTD symptoms after operation, but in 10 (18%) they were unchanged in spite of the control of GER. Patients with a former history of vomiting (n = 38) had better results than those (n = 17) without it (95% of RTD cure v 53%, P less than .001). The success rate in children with recurrent obstructive airway disease (n = 20) was definitely lower than in those without it (n = 35) (70% v 89%, P less than .05). Neither esophageal manometry nor mucosal biopsy provided any predictive clue, but pH studies confirmed that the mean duration of nocturnal episodes of reflux (ZMD) was definitely longer in patients responding favourably to surgical cure of GER than in those in whom this failed (12.2 +/- 9.6 v 3.9 +/- 2.8 minutes, P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640332 TI - Congenital esophageal stenosis due to tracheobronchial remnants: a rare but important association with esophageal atresia. AB - Congenital esophageal stenosis caused by tracheobronchial remnants occurred in eight children, six of whom had associated esophageal atresia and/or tracheoesophageal fistula. Symptoms usually began in early infancy but delayed diagnosis was a common feature. The mean lag period between presentation and definitive operation was 4.6 years (range, 1 month to 16 years). Errors in diagnosis were common. Six were initially diagnosed as having inflammatory strictures secondary to reflux esophagitis. Seven children were subjected to repeated esophagoscopy and bouginage of the "stricture" (mean no. = 3.4), with invariable failure to ameliorate dysphagia. Antireflux procedures were performed in three patients. In all children, symptoms were dramatically relieved following resection of the stenotic segment or esophageal replacement. Although a rare entity, congenital esophageal stenosis due to tracheobronchial remnants should be considered a possibility in patients with esophageal stricture, presumed to be inflammatory in nature, which fails to respond to standard therapy. PMID- 1640333 TI - A new oesophageal tube: assessment of collagen/vicryl composite membrane. AB - Collagen/vicryl composite membrane has been previously shown to be of use in an experimental model as a patch graft in the bladder and oesophagus. Attempts to use it as a circumferential tube graft have been unsuccessful due to the development of strictures at the site of anastomosis. We inserted a polytetrafluoroethylene (PTFE) stented collagen/vicryl bioprosthetic tube into rat omentum, which served as a vascular pedicle. Subsequent histology of the graft showed serial replacement of the bioprosthesis with host collagen and the development of a blood supply. In a second stage procedure, the bioprosthesis was anastomosed to the distal ileum and brought out on the skin to form a fistula. Squamous epithelium was subsequently identified growing the full length of the graft. Therefore, we have developed a vascularised bioprosthetic tube graft which will support the growth of unspecialised epithelium. This model could be of use in bridging congenital atresias or pathological strictures. PMID- 1640334 TI - Long-term endoscopic and flow cytometric follow-up of colon interposition. AB - During 1963 to 1978 colon interposition was performed on 20 children. Early and late mortality accounted for 3 patients and two transplants failed. Of the 15 long-term survivors, subjective results were obtained from 12 patients 12 to 26 years after the reconstruction. Three patients had an excellent subjective result and 9 had a good result. Nine patients underwent esophagogastroduodenoscopy 12 to 26 years after the reconstruction. The endoscopic findings included: marked tortuosity or dilatation (6), pooling of bile or yellow bezoar (3), macroscopic colitis (3), and polyps in the distal anastomosis (2). Only two patients had a straight colon tube without mucosal changes or marked retention. Specimens for histology were obtained in each endoscopy. Colitis was found in 3 patients, 1 patient had gastric metaplasia in the transplant, 1 patient had dysplasia of colonic mucosa and an inflammatory colonic polyp, and in 4 patients histology showed normal colonic mucosa. Flow cytometric samples were obtained from 8 patients. Two showed an aneuploid cell population; the other 6 had normal diploid findings. Because of frequent endoscopic and histological changes, regular endoscopic follow-up of these patients is warranted. PMID- 1640335 TI - Pulmonary vascular abnormalities in experimentally induced congenital diaphragmatic hernia in rats. AB - In infants with congenital diaphragmatic hernia (CDH), abnormalities of the pulmonary arteries are present consisting of increased medial wall thickness and decreased external diameter. This forms the morphological substrate for persistent pulmonary hypertension, one of the leading causes of the high mortality in these patients. To elucidate the significance of these abnormalities, experimental models are required that mimic as close as possible the human situation. In our rat model we are able to study the hypoplastic CDH lungs extensively. In this study we performed a histological evaluation of the pulmonary arterial bed in the control group and the nitrofen-treated group in which the latter was divided into two subgroups, CDH and normal diaphragm. We examined the newborn rats after perfusion of the pulmonary arteries with barium gelatine and subsequent fixation. At the level of the respiratory bronchioles significant differences in the vessels were found consisting of decreased external diameter and increased wall thickness as percentage of the external thickness in CDH lungs compared with controls. Abnormal muscularization of the peripheral branches of the CDH pulmonary arteries was also found. We concluded that the rat model strongly resembles the human situation concerning the arterial bed in the lungs. PMID- 1640336 TI - Pathophysiology of congenital diaphragmatic hernia. III: Exogenous surfactant therapy for the high-risk neonate with CDH. AB - Exogenous surfactant therapy (EST) in surfactant-deficient premature infants has been shown to improve lung compliance, decrease morbidity, and improve survival. Reports have demonstrated that newborns with congenital diaphragmatic hernia (CDH) have lung compliance, pressure-volume curves, and hyaline membrane formation resembling those changes seen in surfactant deficient premature newborns. We hypothesize that EST may also benefit infants with CDH. All high risk cases of prenatally diagnosed CDH at Children's Hospital of Buffalo from November 1988 to February 1991 were prospectively evaluated for EST. In those families who chose to participate, the surfactant preparation, Infasurf (100 mg/kg), was instilled into the newborn's lungs prior to the first breath. The remainder of the perinatal, neonatal, and surgical care was performed in a routine manner. Three high-risk prenatally diagnosed newborns with left CDH were treated with EST. All showed signs of decreased pulmonary compliance, but could still be adequately oxygenated and ventilated. Surgical correction was performed after stabilization and all required patch closures. Two of the three infants suffered no life-threatening episodes of pulmonary hypertension and all survived. These infants had many known indicators for poor outcome in CDH with an expected survival of less than 20%. We believe that EST in these neonates with CDH contributed to their survival with minimum morbidity. These results suggest that surfactant replacement for the high-risk neonate with CDH warrants further consideration and a randomized clinical trial is being planned. PMID- 1640337 TI - Prenatal diagnosis and clinical outcome of ovarian cysts. AB - Technical refinements of ultrasound (US) have greatly affected the antenatal diagnosis and treatment of ovarian cysts. From 1985 to 1990 25 consecutive fetuses with ovarian cysts were followed-up by US both during pregnancy and postnatally. All cases were diagnosed between the 28th and 39th weeks of gestation. Deliveries were all at term; cesarean section was required only for obstetric complications. Eight fetuses (32%) showed US patterns of cyst torsion, a finding confirmed at surgery in all. In five patients US patterns suggested complications postnatally that were also confirmed at operation. In six cases cysts increased or remained unchanged in size after 15 days of life: in 50% of these surgery showed ovarian torsion. In the remaining six cases spontaneous resolution occurred within 1 to 4 months. One patient required intrauterine needle aspiration. There were two cases of intestinal obstruction. To date, more than 60% of newborns with ovarian cysts require oophorectomy; however, different treatments (cystectomy, needle aspiration, uncapping) combined with a close US follow-up are likely to reduce this percentage. PMID- 1640338 TI - Advantages and pitfalls of amnion inversion repair for the treatment of large unruptured omphalocele: results of 22 cases. AB - This is a report of our experience with 22 cases of large unruptured omphaloceles treated by amnion inversion during the period 1973 through 1990. The method is characterized by three stages: (1) a silastic sheet is sutured directly to the skin around the amniotic membrane, under local anaesthesia, without dissection between the skin and the amnion; (2) the reduction of herniated viscera into the abdominal cavity is achieved by squeezing the sheeting using a specially modified stapler; and (3) the amniotic membrane is preserved intact, and inverted into the abdominal cavity at the time of abdominal wall closure. Of the 22 infants, 19 survived with satisfactory results. Two patients died of multiple associated anomalies, and the remaining patient died of sepsis arising at the time of the final abdominal closure. This procedure has proved to be effective and safe for high-risk patients with congenital heart diseases, anal atresia, tracheoesophageal fistula, or bronchial stenosis and prematurity. The practical aspects of the procedure, as well as its advantages and pitfalls, are illustrated. PMID- 1640339 TI - Intestinal vaginoplasty for congenital absence of the vagina. AB - Congenital absence of the vagina is rare and occurs as a result of aplasia of the Mullerian ducts (46,XX) or complete androgen insensitivity syndrome (AIS--46,XY). Both syndromes are associated with normal female external genitalia and these patients are raised as females. These children are usually treated during adolescence with chronic dilatation of the shallow vaginal introitus (pressure tube technique) or by skin graft vaginoplasty (McIndoe procedure). Neither of these procedures is entirely satisfactory, as both may lead to neovaginal stenosis, inadequate length, poor lubrication, or all three. We have recently modified the operation first described by Baldwin in which a loop of sigmoid colon or small bowel is isolated, closed at one end, and brought down on its vascular pedicle as a neovagina and anastomosed to the hymenal ring. We have performed this operation on four adolescents (mean age, 15 years) and two infants (aged 4 days and 14 months) with excellent results (mean follow-up, 7.5 years for the adolescents and 1.8 years for the infants).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640340 TI - Cloacal malformations: experience with 105 cases. AB - A personal experience with 105 cloacal malformations is described, showing the wide range of anatomy that can occur with the urogenital sinus, the vagina(s), and the rectum, as well as in the external features of the perineum. Follow-up is presented on 98 patients, excluding 4 who died preoperatively, 2 who are preoperative, and 1 lost to follow-up but never repaired. Fifty-seven patients had vesicoureteral reflux. Data are given on urinary control, bowel control, and sexual function for those who are now adults. Two have had babies. Operation often requires multiple positions, including the posterior sagittal approach, laparotomy, and lithotomy position. Isolated rectal pull-through should never be performed in these patients, because the urogenital aspects of the malformations are the most difficult to repair and are the most life-threatening to the patient. Six recent cases are presented to illustrate the breadth of the cloacal spectrum. In most of these patients a satisfactory functional result can be achieved for urinary and bowel control as well as sexual function. PMID- 1640341 TI - Fecal continence and quality of life in adult patients with an operated low anorectal malformation. AB - Fecal continence and quality of life were evaluated by a questionnaire in 83 adult patients (mean age, 35 years; 53 women, 30 men) who underwent surgery for a low anorectal anomaly between 1947 and 1963. Fecal continence was assessed by a score described by Holschneider. Seventy-eight healthy people with similar age and sex distributions were used as controls. All controls had good fecal continence, 76% with completely normal bowel function. The aberrations in anal function found in 24% of the controls were minor, such as constipation or occasional slight smearing. Only 60% of the patients who had a low anorectal anomaly had good continence and completely normal bowel function was observed in 15%. Male patients had a slightly better outcome than females. Social problems related to deficient fecal control were reported by 39% of the patients. In addition, 13% of the patients had difficulties in sexual functions. Other health problems were reported by 52% of the patients. Social or sexual problems associated with anal function were not reported by the control population; 6% of them had other health problems. The present controlled study shows that at the adult age, a significant proportion of patients with low anorectal anomalies suffer from deficient fecal control and a diminished quality of life. PMID- 1640342 TI - Long-term anorectal function in imperforate anus treated by a posterior sagittal anorectoplasty: manometric investigation. AB - Thirty imperforate anus patients were investigated by anorectal manometry 5 to 10 years after a posterior sagittal anorectoplasty. Anal resting tone (ART) and anal squeezing pressure (ASP) were subnormal in most patients. Rectal volume (RV) and sensation to balloon distension were within the normal range. Rectoanal reflex inhibition was demonstrated in 9 of 30 patients. Soiling was more common in patients with a very low ART (less than 40 cm H2O) and a low ASP (less than 100 cm H2O). Constipation was more common in patients with a large RV (greater than 150 mL). Still, the correlation to clinical results was incomplete. As regards to the correlation to type of malformation the rectal atresia patients showed near normal results. The vestibular fistula patients were next in results showing rectoanal reflex inhibition in 5/6 patients. There was no difference in the results between bulbar and prostatic fistula patients. PMID- 1640343 TI - Sacrococcygeal teratoma in Sweden between 1978 and 1989: long-term functional results. AB - Thirty-four patients operated with sacrococcygeal teratoma in Sweden between 1978 and 1989 were reviewed. Twenty-five children were available for functional follow up. The patients and their parents were interviewed for bowel and micturition habits. Fourteen patients from this number were subjected to anorectal manometry (56%). Fifteen children reported normal bowel habits (60%). In 10 patients (40%) soiling was observed. However, four of them were under 3 years of age and wearing diapers, which made the functional evaluation difficult. The manometries showed normal and resting tone and squeezing pressures in 10 patients and subnormal values in four patients who also had soiling problems. All investigated children showed normal rectoanal inhibition reflex. Twenty-one patients reported normal micturition, in four (16%) urinary incontinence was recorded. Two of the latter children required intermittent clean catheterization, one was on medication and the last one lives without any treatment. No difference in functional outcome was noted between patients with intrapelvic or extrapelvic tumor location. Retrospectively, it is not possible to know whether the observed functional outcome is due to tumor growth or the result of surgery. Preoperative clinical investigation and in some cases anorectal manometry and cystometry could theoretically resolve this problem. PMID- 1640344 TI - Colorectal carcinoma in children. AB - An increasing incidence of colorectal carcinoma has been noted at this institution. We report seven children with colorectal carcinoma. The average delay between onset of symptoms and diagnosis was 41/2 months, and in five patients distant metastases were present at the first operation. Initial symptoms were ignored in all cases and in only one was the serious nature of the condition realized at first presentation. In five lesions the histology was mucin secreting adenocarcinoma, a poor prognostic variant. All seven died on average 11 months after diagnosis. These three factors--delay in diagnosis, advanced stage of disease, and poorly differentiated histology--contribute overall to a poor prognosis in the young. PMID- 1640345 TI - Volatile sulfur compounds in mouth air from clinically healthy subjects and patients with periodontal disease. AB - Volatile sulfur compounds (VSC) in mouth air were estimated by gas chromatography. The amount of VSC and the methyl mercaptan/hydrogen sulfide ratio were significantly increased in patients with periodontal disease. These two parameters also increased in proportion to the bleeding index and probing depth. A study was also done on the effect of removal of tongue coating on VSC concentrations in mouth air from patients with periodontal involvement. VSC and the methyl mercaptan/hydrogen sulfide ratio were reduced to 49% and 35%, respectively, by removal of the tongue coating. The average amount of tongue coating removed from patients with periodontal disease was significantly higher than from controls (90.1 mg vs. 14.6 mg, p less than 0.01). Estimated production of VSC from tongue coating was 4 times higher than the control value, and the methyl mercaptan/hydrogen sulfide ratio was also markedly increased. However, a saliva putrefaction study suggested that saliva does not contribute to the elevated ratio of methyl mercaptan in mouth air. These results strongly suggest that, in addition to periodontal pockets, tongue coating has an important role in VSC production, in particular leading to an elevated concentration of methyl mercaptan, which is more pathogenic than hydrogen sulfide. PMID- 1640346 TI - A re-evaluation of the distribution of the elastic meshwork within the periodontal ligament of the mouse. AB - The elastic properties of the periodontal ligament have been attributed, in part, to oxytalan fibers, as no other types of elastic fibers are described there. It has been difficult to study the periodontal elastic meshwork by standard microscopic techniques because it is partially obscured by the adjacent periodontal ligament collagen fibers. Our study employed methods which either completely or partially removed mandibular molar periodontal ligament collagen fibers, exposing a previously undescribed periodontal elastic meshwork. The periodontal elastic meshwork was composed of many elastin lamellae containing both peripheral microfibrils of regular arrangement and central microfibrils of irregular arrangement, which could only be demonstrated in oxidized tissues. Peripheral, regularly arranged bundles of microfibrils resembled oxytalan fibers, which were often adherent to the border of the elastin lamella. Elastin lamellae containing irregular microfibrils resembled elaunin fibers. These fibers probably enclosed either blood vessels, nerves or collagen fiber bundles. Peripheral microfibrils attached elaunin to cementum, alveolar bone, blood vessels, and principal periodontal collagen fibers. Thus, the periodontal elastic meshwork is composed of both oxytalan and elaunin fibers. Microfibrils attach elaunin fibers to the adjacent non-elastic tissue and also form bundles which traverse the periodontal ligament space and are probably the oxytalan fibers demonstrable by light microscopic techniques. This meshwork of oxytalan and elaunin fibers probably contributes to tooth support and maintenance of periodontal homeostasis by dissipating chewing forces and maintaining patency of periodontal blood vessels. PMID- 1640347 TI - Effect of interleukin-1 beta on gene expressions and functions of fibroblastic cells derived from human periodontal ligament. AB - The present study shows the effect of interleukin-1 beta (IL-1 beta) on some gene expressions and functions of fibroblastic cells (HPLF) derived from human periodontal ligament. HPLF were used at passages number 5 to 10. IL-1 beta increased DNA synthesis in both a dose- and an incubation time-dependent manner. IL-1 beta in combination with tumor-necrosis factor alpha or transforming growth factor beta synergistically stimulated the DNA synthesis in the cells. Since many studies have shown that the c-myc oncogene is involved in cell proliferation and differentiation, the effect of IL-1 beta on c-myc messenger RNA (mRNA) level in HPLF was examined. IL-1 beta induced a marked c-myc mRNA level in the cells at 90 minutes after initiation of the cytokine treatment. On the other hand, IL-1 beta significantly inhibited alkaline phosphatase (ALP) activity of the cells in a dose-dependent manner. Also an inhibitory effect was observed on the liver/bone/kidney ALP mRNA level of the cells, and this inhibition by IL-1 beta was dose- and incubation time-dependent. These results suggest that IL-1 beta is a regulatory cytokine involved in the regeneration of the human periodontal ligament. PMID- 1640348 TI - Ultracytochemical localization of basal lamina anionic sites in the rat epithelial attachment apparatus. AB - The basal lamina anionic sites of the epithelial attachment apparatus (EAA) were investigated at the electron microscopic level in adult rat periodontium. After 1M NaCl junctional epithelium detachment, an irregular and fluffy basal lamina like structure appeared to cover the cementum surface. This structure reacted positively with polyethyleneimine (PEI), a strongly cationized ultrastructural tracer, appearing to be composed of highly electron-dense microaggregates. Depending on section plane, double-tracked structures of undefined length were found within PEI precipitates and closely related to cementum collagen fibrils. After nitrous acid de-N-sulphation, 8 nm wide sets of two parallel lines were clearly identified. "Double tracks", i.e., sets of paired lines with peripherical PEI electron-dense material, were found to self-assemble to form dimers, clusters or more complex organizational patterns. From sensitivity towards nitrous acid oxidation and positive control observations, it was concluded that basal lamina anionic sites in the EAA, represented by PEI microaggregates, contain heparan sulfate proteoglycans (HSPGs). Furthermore, high resolution ultrastructural images demonstrated that HSPGs adopt a morphological appearance of "double tracks" in the tissue. On the other hand, the present findings suggest that HSPGs clusters, never found in the mucosal basement membrane used as positive control, may be related to a functional specificity of the tissue at the dento-gingival junction. PMID- 1640349 TI - Numbers and vitality of leukocytes in pocket washings of untreated periodontitis lesions in humans utilizing a novel intracrevicular lavage technique. AB - The purpose of the present study was to develop an intracrevicular lavage technique, and to use it for assessment of the total number and % of vital leukocytes from untreated periodontitis pockets. A lavage device was developed, consisting of specially crafted cannulas, a vacuum pump and a charge amplifier. In vivo evaluations showed that there was a linear relationship between lavage time and lavage volume; 2-6 lavage samples were obtained from each of 20 patients with untreated advanced periodontitis, and the lavage time was measured in a subsample of 16 pockets. The lavage fluid was centrifuged, and the supernatant was separated from the cellular components. The cells were vital-stained using two methods, trypanblue exclusion method (TB) and ethidium-bromide fluorescein diacetate stain (EB-FDA). Numbers of vital and non-vital leukocytes per sample were assessed using a Neubauer chamber. The number of erythrocytes per sample was evaluated using the same counting method. The results included 95 samples obtained from the 20 patients: 76% of all samples ranged in pocket depth between 4 and 8 mm. The lavage technique provided an overall mean lavage volume of 282.37 microliters in an average time of 16.44 seconds. The mean number of leukocytes per sample was 22.20 x 10(3) (TB) and 24.48 x 10(3) (EB-FDA). Percent vital leukocytes were 72.27 (TB) and 72.63 (EB-FDA). EB-FDA had a lower counting error than TB. The low erythrocyte counts per sample suggested that subgingival bleeding during sampling was negligible. Spearman correlation coefficients showed weak associations between pocket depth and leukocyte counts, % of vital leukocytes and erythrocytes. Due to the short sampling time this new intracrevicular sampling technique permits sampling of pockets before the tissue responds to the stimulus of the lavage device, and provides subgingival washings with high numbers of leukocytes. PMID- 1640350 TI - Platelet-derived and insulin-like growth factors stimulate regeneration of periodontal attachment in monkeys. AB - Regeneration of cementum, ligament, bone and new attachment was achieved by introducing mixtures of recombinant human platelet-derived growth factor and insulin-like growth factor into debrided lesions of experimentally induced periodontitis in monkeys. This growth factor therapeutic regimen induced the regeneration of nearly 50% of the lost attachment within 4 weeks. New attachment in some cases included regeneration of horizontally resorbed interdental septa. These observations suggest that predictable, clinically significant gains in new attachment may be possible through the use of highly purified human recombinant growth factors delivered to debrided lesions of adult periodontitis in appropriate, inert carrier vehicles. PMID- 1640351 TI - Epidermal growth factor expression in junctional epithelium of rat gingiva. PMID- 1640352 TI - Acute response of periodontal ligament blood flow to external force application. PMID- 1640353 TI - Influence of age-dependent pharmacokinetics and metabolism on acetaminophen hepatotoxicity. PMID- 1640354 TI - Pharmacokinetics of cyclosporine in bone marrow transplantation: longitudinal characterization of drug in lipoprotein fractions. AB - The pharmacokinetics of cyclosporine (CSA; 2 mg/kg given iv over a period of 2 h every 12 h) in whole blood, plasma, high-density lipoproteins (HDL), and low density lipoproteins (LDL) were studied after single (n = 10) and multiple (31 days; n = 6) doses in patients receiving allogeneic bone marrow transplants. Whereas HDL-cholesterol levels decreased significantly, LDL-cholesterol levels increased from day 1 to day 31 of CSA dosing. The mean area under the concentration-time curve and half-life values of CSA in whole blood or total plasma did not differ after single or multiple doses. Greater amounts of CSA were contained in the HDL relative to the LDL fraction over the 24-h period after a single dose; the reverse was found after multiple dosing. Cyclosporine was not detectable in the very LDL fractions. The percentage of total plasma CSA contained in each lipoprotein fraction was independent of the concentration of CSA in total plasma or whole blood. The pharmacokinetics of CSA in the various biologic matrices were not associated with measurements of kidney and liver function. Taken together, the variability of CSA pharmacokinetics previously reported in whole blood or total plasma was also found in lipoprotein fractions. The relative changes in CSA content of lipoproteins may offer an explanation for differences in drug effect with multiple dosing. PMID- 1640355 TI - Erythrocytes as a total barrier for renal excretion of hydrochlorothiazide: slow influx and efflux across erythrocyte membranes. AB - The potential barrier effect of erythrocytes (RBC) on renal excretion (mainly by tubular secretion) of hydrochlorothiazide (HCTZ) was evaluated in nine anesthetized rats during steady-state iv infusion. Drug concentrations in plasma and blood from the carotid artery and renal vein were assayed by a simple modified HPLC method. Renal extraction ratios were concentration-independent with a mean of 0.17 +/- 0.05 (SD). The renal excretion was found to occur primarily from the drug in plasma; the mean net fractional removal from plasma was 0.57 +/- 0.12, while that from RBC was less than 0.008 +/- 0.041. The virtual total unavailability of HCTZ from RBC (containing approximately 70% of drug in arterial blood) for renal excretion is attributed to relatively slow efflux of drug from RBC to plasma during each passage through the kidney compared with the blood transit time (in seconds). Preliminary in vitro influx and efflux kinetics of HCTZ across RBC membranes were studied using rat and human blood. The flux data could be adequately described by a linear, reversible, closed two-component system model, and the mean equilibration half-times (ET1/2) in rat and human blood were 10.9 and 20.5 min, respectively. The mean residence time of drug in blood circulation of rats was estimated to be 8.32 +/- 1.06 min, which is shorter than the ET1/2. This is consistent with data indicating that distribution equilibrium of HCTZ in arterial blood might not be reached in vivo even at steady state. Other implications of slow transport kinetics of drugs across RBC membranes are discussed. PMID- 1640356 TI - Effect of nasolacrimal occlusion on timolol concentrations in the aqueous humor of the human eye. AB - We studied the effect of manual nasolacrimal occlusion on the concentration of timolol in the aqueous humor of eyes of patients undergoing cataract extraction. Aqueous humor samples were obtained at various times after timolol maleate instillation from patients with or without 5 min of nasolacrimal occlusion; aliquots were assayed by HPLC. In patients receiving occlusion treatment, average timolol concentrations were statistically greater than those in control patients both between 15 and 90 min after instillation and also at 180 min. Pharmacokinetic analysis indicated that occlusion increased the concentration of timolol in the aqueous humor 1.7 times. In both groups, timolol concentrations were highest approximately 1 h after instillation. The decline in aqueous humor timolol concentrations occurred at similar rates in both groups. PMID- 1640357 TI - Human pharmacokinetics of ibuprofen enantiomers following different doses and formulations: intestinal chiral inversion. AB - The influences of absorption rate and dosage size on the pharmacokinetics of ibuprofen (IB) enantiomers were studied in six healthy subjects. Rapidly absorbed solutions (50, 100, 200, 400, 600, and 1200 mg) and regular 600-mg tablets of racemic IB were given orally, and plasma concentration-time courses of the enantiomers were followed. Solutions were absorbed faster (tmax less than 0.25 h) than the tablet (tmax = 2.17 +/- 1.17 h). While the S:R AUC ratios were unaffected by increasing the dose, they were significantly greater after the tablet (1.35 +/- 0.14) as compared with the solutions (1.15 +/- 0.16 to 1.24 +/- 0.26). This indicates a greater extent of chiral inversion for the tablet, perhaps due to a longer residence time in the gut, thereby allowing more presystemic inversion. To test this hypothesis, R-IB was incubated at 37 degrees C in the presence of excised segments of human ileum and colon obtained from three patients. Chiral inversion was evident in all segments. After 3 h, the extent of inversion ranged from 20.0 to 33.0%. In addition, incubation resulted in the formation of up to 23.3 and 13.0% of acylglucuronides of S- and R-IB, respectively. In all subjects, the AUC-dose relationships were nonlinear, indicating a gradual increase in the clearance of both enantiomers due, perhaps, to a parallel saturation of plasma protein binding sites. In humans, the chiral inversion of IB is not influenced by the dosage size but is enhanced by prolongation of the residence time in the intestine. PMID- 1640358 TI - Stereoselective hydrolysis of O-acetyl propranolol as prodrug in rat tissue homogenates. AB - The stereochemical characteristics of the hydrolysis of O-acetyl propranolol were studied using phosphate buffer (pH 7.4), rat plasma, and rat tissue homogenates. In the phosphate buffer, no difference was observed in the hydrolysis rate between the esters of (R)- and (S)-propranolol. In rat plasma and tissue homogenates, hydrolysis of the ester was both accelerated and stereoselective. Hydrolysis of O-acetyl (R)-propranolol was five times faster than that of the (S) isomer in rat plasma. However, in the liver and intestine homogenates, the (S) isomer was hydrolyzed faster than the (R)-isomer. Interconversion between the (R) and (S)-isomers was not observed under the experimental conditions. The same stereoselective hydrolysis was also observed with racemic O-acetyl propranolol. However, observed rate constants for the hydrolysis were lower than those for the pure isomers. These results indicate that enzymatic hydrolysis of O-acetyl propranolol occurred stereoselectively and the selectivity of the plasma enzyme was different from those of liver and intestine enzymes. PMID- 1640359 TI - Pharmacokinetic-pharmacodynamic modeling: time-dependent protein binding--an alternative interpretation of clockwise and counterclockwise hysteresis. AB - Development of effect compartment model theory has greatly enhanced our understanding of the relationship between pharmacokinetics and pharmacodynamics. When effect versus concentration in serum (usually total concentration) is plotted and counterclockwise hysteresis is observed, an initial disequilibrium between receptor(s) and serum is generally presumed and an effect compartment model is used; alternatively, clockwise hysteresis may infer tolerance, which may be characterized by an adaptation model. In this simulation study, the influence of time-dependent binding to serum protein on the relationship between effect and concentration in serum was investigated. In these simulations, time-dependent protein binding occurred as a result of an increase in protein concentration in serum or displacement by a metabolite. When concentration of free drug in serum was responsible for the pharmacological response, and response versus total drug concentration in serum was plotted, counterclockwise hysteresis, consistent with an effect compartment, occurred with a time-dependent decrease in binding to serum protein. Clockwise hysteresis, consistent with tolerance, occurred with a time-dependent increase in binding to serum protein. For both sets of simulations, no hysteresis was observed when response was plotted against concentration of free drug in serum. These results indicate that, when response is related to concentration of free drug, measurement of concentration of free drug may allow a clearer interpretation of the pharmacokinetic-pharmacodynamic relationship. PMID- 1640360 TI - Effect of basic cholane derivatives on intestinal cholic acid metabolism: in vitro and in vivo activity. AB - A representative series of hydroxy-5 beta-cholanyl-24-amines were tested both in vitro and in vivo with respect to their activity against the intestinal bacteria responsible for bile acid metabolism. For the in vitro studies, radiolabeled [14C]cholic acid was incubated with human stools both in aerobic and anaerobic conditions in the presence of the title compounds at a dose of 10 micrograms/mL, and the biotransformation of cholic acid into radiolabeled deoxycholic acid and other metabolites was followed by TLC-radiochromatography. Of the compounds studied, 3 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-N-methylamine showed the highest activity. This compound was used for the in vivo studies and was shown to inhibit the formation of endogenous secondary bile acids when chronically administered to rats at a dose of 60 micrograms/day for 15 days. The treated rats showed an increased ratio of taurocholic acid (primary bile acid) to taurodeoxycholic acid (secondary bile acid) in bile, a fact further suggesting a potent antibacterial activity of the compound toward bacteria responsible for bile acid metabolism. PMID- 1640361 TI - Pharmacokinetic studies of N-butyric acid mono- and polyesters derived from monosaccharides. AB - The pharmacokinetics of seven butyric esters derived from monosaccharides were studied after iv administration of a bolus dose to rabbits. Results obtained showed that a constant plasma level of butyric acid is maintained due to the slow disappearance of butyric acid esters from the plasma in contrast to the case of salts, such as arginine butyrate, which are rapidly cleared. The maintenance of these covalent compounds in the body can increase concentrations of n-butyric acid in the tumor area for more efficient chemotherapy. These results seem to be directly related to the in vitro anticellular activity of butyric esters and the prolonged therapeutic protection in tumor-bearing animals. PMID- 1640362 TI - Performance of a modified starch hydrophilic matrix for the sustained release of theophylline in healthy volunteers. AB - Two experimental formulations of theophylline with a hydrophilic starch matrix were evaluated for their sustained-release characteristics after single administration in healthy human volunteers. Theo-dur was chosen as a reference sustained-release formulation. In a first study, the extent of absorption was similar for a syrup, for Theo-dur, and for the experimental formulation of theophylline with 70% drum-dried corn starch as the sustained-release agent (DDCS 70). The maximal plasma concentration (Cmax) was significantly lower, and the time to reach Cmax as well as the time span during which the plasma concentration was at least 75% of the Cmax were significantly higher for Theo-dur than for the DDCS-70 formulation. A sustained-release profile, as for Theo-dur, was not reached for DDCS-70. In a second study the influence of the starch:drug ratio on the bioavailability was investigated. The decrease in starch content from 70 to 50% of the formulation did not improve the plasma concentration-time profile towards a sustained-release profile. PMID- 1640363 TI - Liposomes containing fluorinated steroids: an analysis based on photon correlation and fluorine-19 nuclear magnetic resonance spectroscopy. AB - Small unilamellar liposomes containing fluorinated steroids (flumethasone and dexamethasone) were obtained. A physicochemical evaluation was conducted based on photon correlation spectroscopy (PCS) and fluorine-19 (19F) nuclear magnetic resonance (NMR) spectroscopy compared with standard biochemical methods (HPLC). The PCS method provides a fast and adequate evaluation of some critical features of liposomes (size, physical stability). In addition, 19F NMR spectroscopy gives substantial information, in a nondestructive manner, on steroid behavior in the membrane upon encapsulation and also when the temperature of liposomes is increased. The combined spectroscopic approach proposed here might prove useful in (1) the management of liposomal formulation, especially in the documentation of physicochemical properties, (2) pharmaceutical control in the industrial production line, and (3) control preceding injection at the clinical site. Spectroscopic techniques might offer a complementary approach to classical biochemical methods in the evaluation of the properties of a liposomal formulation and could be usefully integrated into quality control procedures. PMID- 1640364 TI - Propranolol disposition in the rat: variation in hepatic extraction with unbound drug fraction. AB - The plasma protein binding of propranolol has been described as nonrestrictive for its hepatic extraction to explain the observation that propranolol is efficiently removed by the liver, in spite of extensive protein binding. The present study was designed to examine the relationship between propranolol protein binding, metabolism by isolated hepatocytes, and extraction by the isolated perfused rat liver. In isolated hepatocytes, the intrinsic clearance of free drug increased three- to fourfold as albumin and alpha 1-acid glycoprotein (AAG) concentrations increased, suggesting that albumin and AAG facilitate the elimination of propranolol by hepatocytes. In the isolated perfused liver, propranolol extraction was almost complete (E = 0.996) in the absence of albumin and AAG. With 40 g/L of albumin and 2 g/L of AAG in the perfusate, the free fraction of propranolol decreased to 0.031, but extraction remained high (E = 0.960). With 40 g/L of albumin and 10 g/L of AAG in the perfusate, the free fraction further decreased to 0.014 and extraction dropped sharply (E = 0.820). The observed relationship between propranolol extraction and the free fraction of propranolol was in good agreement with that predicted using estimates of intrinsic clearance measured in isolated hepatocytes suspensions. These data indicate that propranolol extraction is sensitive to changes in binding at very low free fraction values and suggest a facilitation of propranolol clearance by albumin and AAG. PMID- 1640365 TI - Factors affecting in vitro protein binding of etoposide in humans. AB - Clinical studies have demonstrated that the plasma protein binding of etoposide, a widely used anticancer drug, is extensive (approximately 94%), highly variable among patients (10-fold range), and significantly related to serum albumin and total bilirubin concentration. The present study was designed to more thoroughly evaluate factors likely to affect etoposide protein binding under controlled in vitro conditions where single variables could be changed. Protein binding was determined using an equilibrium dialysis method with tritiated etoposide. The binding of etoposide was similar in serum or plasma, and heparin had no effect on binding. Etoposide binding decreased with increased pH, but no clinically significant difference was noted within the range of physiologic pH. Etoposide binding evaluated in single-source donor plasma was concentration-dependent over a concentration range of 1 to 250 micrograms/mL. Etoposide binding parameters determined in normal human plasma were characterized by a single class of binding sites of moderate affinity (K = 2.88 +/- 0.47 x 10(4)) and high capacity (nP = 5.07 +/- 0.5 x 10(-4); where n is the number of binding sites). The etoposide binding ratio was significantly correlated with albumin concentration (r2 = 99%, p less than 0.05). The characteristics of etoposide binding in a 4.0-g/dL solution of human serum albumin (K = 3.56 +/- 1.22 x 10(4) and nP = 5.58 +/- 0.16 x 10(-4)) suggest that the single class of binding sites is on albumin. Bilirubin caused a significant decrease in K, consistent with competitive binding, but only at higher bilirubin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640366 TI - Experimental studies of transient mass transfer and reaction in the liver: interpretation with a heterogeneous compartment model. AB - The uptake and metabolism of lipophilic compounds by the liver were studied by administering a model compound, lidocaine, to the isolated rat liver. Lidocaine was continuously infused into the liver until steady state was reached. Subsequent step changes in the inlet concentration were used to obtain information on rates of cellular uptake and release and to assess the extent of mixing within the organ. A simple heterogeneous model combining mass transfer and enzyme reactions was required to simulate the effluent levels of lidocaine and two primary metabolites, monoethylglycinexylidide and 3-hydroxylidocaine. The rate constants for uptake and release of lidocaine were 1200 and 46 min-1, respectively. The rate-limiting step was intracellular reaction, with a rate constant of 0.49 min-1. Although the rate of lidocaine uptake was fast, it was 50 times slower than the rate of facilitated uptake of galactose, a fact suggesting passive transport of lidocaine between the tissue and the vasculature. The rates of mass transfer of lidocaine and its metabolites differed, but the ratios of the rate of uptake to the rate of release were the same. The results suggested that all three species had an affinity for the cellular region of the liver; concentrations in tissue were approximately five times greater than concentrations in effluent. Because of the large capacity of the organ for uptake of lidocaine and its metabolites, concentrations from washout experiments were controlled by linear mass transfer from the tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640367 TI - An extended version of a novel method for the estimation of partition coefficients. AB - Using the semi-empirical AM1 method, 302 compounds have been studied and equilibrium properties calculated. Functions based on linear combinations of subsets of calculated properties have been fit to the 1-octanol-water partition coefficients. The best such semi-empirical approach function has 18 parameters, has a standard deviation of 0.306, and seems to describe the partition coefficients of the 302 compounds. The predictive power of the function was tested and found to be good. Since this new version is based on a much larger number of, and structurally more varied, compounds and uses an improved, new function, we expect it to be a very useful method to predict partition properties of a wide variety of compounds. PMID- 1640368 TI - Dissolution of fludrocortisone from phospholipid coprecipitates. AB - The physical properties and dissolution behavior of phospholipid coprecipitates of fludrocortisone acetate (FA) prepared from ethyl acetate, as well as the effect of added polymer, have been determined. The fraction dissolved after 90 min and the initial dissolution rate (IDR) of coprecipitates containing dimyristoyl phosphatidylcholine (DMPC) (4:1, w/w; FA:DMPC) were 77% and 3.5-fold greater than for FA at pH 2.0 and 37 degrees C. The mechanisms of dissolution were similar to those previously established for griseofulvin, but no aging occurred over 4 months at room temperature in a desiccator. The addition of 0.01 mol% of dextran (MW = 2 million) or 0.1 mol% of poly(lactic acid) reduced the fraction of FA dissolved in 90 min by 15% and reduced the IDR by 35%. The addition of poly(vinylpyrrolidone) (PVP) resulted in a minimum of dissolution efficiency at 1 mol% of PVP 10 (MW = 10,000) or PVP 24 (MW = 24,000) and at 0.1 mol% PVP 40 (MW = 40,000). Only PVP 24 influenced the melting point and heat of fusion of the coprecipitates (determined by differential thermal analysis). Coprecipitate dissolution was reasonably described by either second-order or Weibull distribution kinetic models. These results support the application of high drug-containing solid dispersions using phospholipids to increase the dissolution behavior of poorly water-soluble drug solvates and the possibility of modifying drug release by the incorporation of small amounts of polymers. PMID- 1640369 TI - First-derivative spectroscopic determination of binding characteristics of rifampicin to human albumin and serum. AB - A first-derivative spectroscopic method for the simultaneous determination of bound and unbound drug in human serum and serum albumin solution was developed. As an example, the binding characteristics of rifampicin were studied. In serum albumin solution, the rifampicin bound and unbound fractions were determined at 473.5 and 475.8 nm, respectively. For human serum, the unbound fraction was determined at 479.4 nm. The results obtained by the first-derivative spectroscopic method were in agreement with those obtained by equilibrium dialysis. The proposed method is very simple and accurate when applied to measurements of drug:protein binding. Moreover, it allows a direct measurement of the bound and unbound forms without any physical separation. PMID- 1640370 TI - Punch geometry and formulation considerations in reducing tablet friability and their effect on in vitro dissolution. AB - The tablet friability resulting from formulation variations was studied under controlled granulation moisture content and tablet crushing strength. Tablets made with lactose were more friable than tablets made with microcrystalline cellulose. Replacement of 0.5% magnesium stearate with 0.5% stearic acid in the formula reduced tablet friability, whereas the combination of 0.5% stearic acid and up to 0.25% magnesium stearate did not increase tablet friability, decrease drug dissolution rate, or increase tablet-to-tablet variability in dissolution. Tablets compressed with extra deep concave punches resulted in lower friability compared with tablets compressed with standard concave or deep concave punches. The friabilities of the standard convex and deep convex tablets were similar, indicating that a critical level of punch tip curvature was important in reducing tablet friability. The dissolution rate was not affected by the punch tip geometry, but the tablet-to-tablet dissolution variability at the 0.5% stearic acid level for the extra deep convex tablets was higher compared with the standard convex tablets. PMID- 1640371 TI - Effects of structural variations on the rates of enzymatic and nonenzymatic hydrolysis of carbonate and carbamate esters. AB - The effect of structural variations on the rates of elastase-catalyzed hydrolysis of model carbonate and carbamate esters was studied using HPLC. It is shown that branching in the immediate vicinity of the carbonate or carbamate functionally results in decreased hydrolysis rates. Whereas aryl carbonates act as substrates for elastase, p-nitrophenyl butyl carbamate inhibits the enzyme. A novel method was developed for the entrapment and quantitation of 14CO2 produced upon hydrolysis of carbonyl-14C-labeled carbonate esters. This technique could be useful in studying the mechanism of enzymatic hydrolysis of this type of compound and has the potential of being adapted as a convenient method in the assessment of estrolytic activity of tissue homogenates. PMID- 1640372 TI - Stability studies of topical carbonic anhydrase inhibitor 6-hydroxyethoxy-2 benzothiazole sulfonamide. AB - A new carbonic anhydrase inhibitor, 6-hydroxyethoxy-2-benzothiazole sulfonamide (6-hydroxyethyoxyzolamide), was studied to determine its stability in aqueous solution from pH 2.9 to 9.2 at a constant ionic strength of 0.15 M. This newly synthesized derivative of ethoxyzolamide has demonstrated clinical efficacy for use as an ophthalmic drug to lower intraocular pressure. Drug solution in sealed ampules was placed in a constant temperature over either at two temperatures (75 and 85 +/- 0.2 degrees C) or four temperatures (75, 80, 85, and 90 +/- 0.2 degrees C). Samples were analyzed by known HPLC methods. The results indicated that 6-hydroxyethoxyzolamide is most stable at pH 4 to 5.5. The aqueous drug solutions at pH 7.0 and 8.0 were, nevertheless, sufficiently stable, based on extrapolation of kinetic data at high temperatures using the experimentally determined Arrhenius equation. The degradation compound was identified by spectral analysis to have a hydroxyl group substituting for the original -SO2NH2 group. PMID- 1640373 TI - Statistical approaches to stability protocol design. AB - In stability protocols, data are usually visualized as being generated, and stability evaluation is accomplished at a point in time when sufficient data have been accumulated. Often, data are simply treated by the "statistically best fit" and, as a consequence, statements describing some batches as being first order and some being zero order are frequently used. From a scientific point of view, it is more advantageous at the preformulation stage to ascertain what the stability profile should be (i.e., what the mechanism is) and then apply the statistics to this format. Examples are given of pH profiles, Arrhenius plotting, and dissolution data. In the first case, the use of fractional factorials (a matrix approach) is suggested. PMID- 1640374 TI - Modification of the crescentic osteotomy for hallux valgus correction. A preliminary report. AB - A new proximal osteotomy for hallux valgus correction, which has several advantages, is presented. These advantages include good stability; ease of rigid, two-point internal fixation; accurate, reproducible correction of the intermetatarsal angle; minimal shortening or elevation of the metatarsal; and early weightbearing. Preliminary results on 12 feet of 12 patients over a 3-year period have been encouraging and may indicate that this osteotomy is a viable alternative when considering proximal osteotomy for correction of hallux valgus. PMID- 1640375 TI - Bone graft reconstruction of a flail digit. AB - The author presents a case report with a 1-year follow-up period demonstrating successful bone graft stabilization of an iatrogenic flail second toe. The author discusses the techniques for calcaneal autogenous bone grafting for reconstruction of the iatrogenic shortened toe combined with ancillary procedures to improve the digital length pattern. After 18 months, this staged approach to stabilization of the digit and realignment of the digital length pattern appears to be successful. PMID- 1640376 TI - Shaping a life-style of independence. Abilities, aging, and environmental design. AB - What makes our own aging so interesting and predictions about normative aging profiles so difficult is that there are many different capacities that may be altered. The composite pattern of strengths and needs and of the degree of need has yet to be described. This makes predictions about what people can or could do difficult. Each individual represents a mosaic of capacity and loss resulting from the impact of capacities such as vision, hearing, response time, posture, gait, energy level, and even recall and the demands placed upon them by their individual circumstances, life-styles, and environments. A person with major memory loss and tremendous energy may be different from one who experiences slight losses in vision, hearing, mobility, agility, and a crystal clear memory. Their behavioral changes may be more evident in strange environments than in familiar ones. This mosaic of capabilities and needs makes traditional interventions that are focused on a singular disability or major diagnostic conditions difficult. Traditional rehabilitation methods need to be adapted to grapple with the diversity of older people functioning in a community. Adaptations in our understanding of people, activities, and environments will put us in a better position to facilitate the normal interactions of older people in senior centers and, importantly, in public intergenerational settings. Older people have not been well served by services, programs, and legislation that have focused on single disabilities or devices.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640377 TI - Metabolic and hemodynamic responses to concurrent voluntary arm crank and electrical stimulation leg cycle exercise in quadriplegics. AB - This study determined the metabolic and hemodynamic responses in eight spinal cord injured (SCI) quadriplegics (C5-C8/T1) performing subpeak arm crank exercise (ACE) alone, subpeak functional electrical stimulation leg cycle exercise (FES LCE) alone, and subpeak FES-LCE concurrent with subpeak ACE (hybrid exercise). Subjects completed 10 minutes of each exercise mode during which steady-state oxygen uptake (VO2), pulmonary ventilation (VE), heart rate (HR), cardiac output (CO), stroke volume (SV), mean arterial pressure (MAP), arteriovenous oxygen difference (a-v O2 diff), and total peripheral resistance (TPR) were determined. Although mean VO2 for both ACE alone and FES-LCE alone was matched at 0.66 l/mi, individualized power outputs ranged from 0-30 W (mean = 19.4 +/- 1.3) and 0-12.2 W (mean = 2.3 +/- 0.6), respectively. Hybrid exercise elicited significantly higher VO2 (by 54 percent), VE (by 39-53 percent), HR (by 19-33 percent), and CO (by 33-47 percent), and significantly lower TPR (by 21-34 percent) than ACE or FES-LCE performed alone (P less than or equal to 0.05). Stroke volume was similar between hybrid exercise and FES-LCE alone, and these two exercise modes evoked a significantly higher SV (by 41-56 percent) than during ACE alone. These data clearly demonstrate that hybrid exercise creates a higher aerobic metabolic demand and cardiac-volume load in SCI quadriplegics than either subpeak levels of ACE or FES-LCE performed separately. Therefore, hybrid exercise may provide more advantageous central cardiovascular training effects in quadriplegics than either ACE or FES-LCE alone. PMID- 1640378 TI - Biomechanical analysis of wheelchair propulsion for various seating positions. AB - The pattern of propulsion was investigated for five male paraplegics in six seating positions. The positions consisted of a combination of three horizontal rear-wheel positions at two seating heights on a single-purpose-built racing wheelchair. To simulate wheelchair propulsion in the laboratory, the wheelchair was mounted on high rotational inertia rollers. For three trials at each seating position, the subjects propelled the designed wheelchair at 60 percent of their maximal speed, which was determined at the beginning of the test session. At each trial, the propulsion technique of the subject was filmed at 50 Hz with a high speed camera for one cycle, and the raw electromyographic (EMG) signal of the biceps, brachii, triceps brachii, pectoralis major, deltoid anterior, and deltoid posterior muscles were simultaneously recorded for three consecutive cycles. The digitized film data were used to compute the angular kinematics of the upper body, while the EMG signals were processed to yield the linear envelope (LE EMG) and the integrated EMG (IEMG) of each muscle. The kinematic analysis revealed that the joint motions of the upper limbs were smoother for the Low positions since they reached extension in a sequence (wrist, shoulder, and elbow), when compared to the High positions. Also, the elbow angular velocity slopes were found to be less abrupt for the Backward-Low position. It was observed that in lowering the seat position, less IEMG was recorded and the degrees of contact were lengthened. Among the seat positions evaluated, the Backward-Low position had the lowest overall IEMG and the Middle-Low position had the lowest pushing frequency. It was found that a change in seat position caused more variation in the IEMG for the triceps brachii, pectoralis major, and deltoid posterior. The trunk angular momentum was not found to be affected by a change in seat position which may be related to the variability among the subject's technique of propulsion or to a posture compensation. PMID- 1640379 TI - The contribution of selected anthropometric and physiological variables to 10K performance of wheelchair racers: a preliminary study. AB - The purpose of this study was to determine the relationship between selected anthropometric and physiological variables and 10K time. Eleven male wheelchair athletes with spinal cord injuries in training for national competition performed continuous progressive exercise tests on a wheelchair ergometer to determine maximal metabolic and cardiorespiratory values. Anthropometric data were also collected. The laboratory data were analyzed for correlation with the best 10K time of each subject during the test period. The subjects averaged 27 min 30 sec for their 10K races, 2.49 L.min-1 for VO2max and 35 percent for maximal gross mechanical efficiency during submaximal exercise. Speed at peak oxygen consumption (r = -0.66), gross mechanical efficiency (r = -0.56), and body density (r = -0.57) was found to be significantly (p less than 0.10) correlated with 10K time. The results show very little correlation between VO2max and 10K time (r = 0.02). Further study is indicated for the relationship between gross mechanical efficiency, speed at maximal oxygen consumption, body density, and 10K time; these variables may be useful in evaluating training programs for improving race performance. PMID- 1640380 TI - A computer-aided socket design procedure for above-knee prostheses. AB - A computer-aided socket design procedure (CASD) has been developed whereby an above-knee socket shape can be created based on anthropometric measurements taken from an amputee. The anthroometric measurements are used to select a subset of three reference shapes from a Reference Shape Library stored in the computer in the form of three-dimensional numerical data. Transformation procedures then scale the reference shapes at each cross-sectional level to match the amputee's cross-sectional areas. Blending of the three shapes is determined by tissue mass weighting factors, to yield a single custom socket configuration, known as the "basic socket shape." Subsequent graphical procedures in the CASD system allows further sculpting of the shape in the form of interactive adjustments of the numerical data to reach the socket shape desired by the prosthetist. The resultant shape data can then be transferred to a computer numerically controlled (CNC) milling machine to carve a model of the socket shape. PMID- 1640381 TI - A two-step segmentation method for automatic recognition of speech of persons who are deaf. AB - The development and use of a two-step word segmentation method for automatic recognition of the speech produced by deaf persons are described in this paper. This method incorporates the segmental and temporal characteristics of deaf speech, particularly the intra- and inter-word pauses, to achieve accurate recognition. In the first step, estimates of word boundaries were obtained by detecting these pauses. In the second step, the word boundaries were determined by matching all possible groupings of speech segments against all reference templates during recognition. This method was applied to recognition of isolated words and connected-speech utterances produced by two deaf speakers. Recognition rates of 93.01 percent and 81.81 percent were obtained in recognizing isolated words and connected speech, respectively. PMID- 1640382 TI - Computer as a group teaching aid for persons who are blind. AB - A concept has been formulated whereby a teacher in a classroom for students who are blind can communicate line diagrams and text directly to the students. This approach is based upon a single computer placed on the teacher's desk, with monitors on the students' desks. Access to the information displayed on the monitors is obtained by means of an optoelectronic sensor and vibrotactile output. Two versions of the sensor have been made--one for sensing line diagrams, and the other for Braille text. A simple, low-cost arrangement has also been designed by which students who are blind can prepare a hard copy of the diagrams from the monitor display. The special feature of the system is that it allows the teacher to convey information directly to the students, that is, diagrams and text that have been entered into the computer while the students are in the classroom. Information previously stored on floppy disks may also be communicated in this way. This methodology will overcome the current limitation where the teacher is able to hand out only embossed diagrams and text that have been previously prepared. Learning to use the new system can be accomplished in a short time, with the added advantage that the system is relatively inexpensive. PMID- 1640383 TI - Phylogenetic analysis of the Diplomonadida (Wenyon, 1926) Brugerolle, 1975: evidence for heterochrony in protozoa and against Giardia lamblia as a "missing link". AB - A suite of 23 ultrastructural characters was used in a phylogenetic analysis of the protozoan order Diplomonadida. A single most parsimonious solution was found, with a length of 38 transformations and a consistency index of 0.84. The cladogram supports previous hypotheses of the relationships of the genera in the suborder Diplomonadina, as well as the inclusion of the genera Enteromonas and Trimitus in the order. Heterochrony is suggested in the change to binary axial symmetry, as hypermorphosis resulting from delayed cytokinesis in the ancestor. Hypotheses regarding a pivotal position for Giardia lamblia in the evolution of eukaryotes are inconsistent with the phylogeny proposed here. PMID- 1640384 TI - Identification of Tetrahymena ciliary surface proteins labeled with sulfosuccinimidyl 6-(biotinamido) hexanoate and Concanavalin A and fractionated with Triton X-114. AB - Tetrahymena thermophila cells were labeled with sulfosuccinimidyl 6-(biotinamido) hexanoate, a sensitive nonradioactive probe for cell surface proteins, and Western blots of axonemes and ciliary membrane vesicles were compared to cilia fractionated with Triton X-114 (TX-114) in order to study the orientation of ciliary membrane proteins. Greater than 40 ciliary surface polypeptides, from greater than 350 kDa to less than 20 kDa, were resolved. The major surface 50-60 kDa proteins are hydrophobic and partition into the TX-114 detergent phase. Two high molecular weight proteins, one of which is biotinylated, comigrate with the heavy chains of ciliary dynein, sediment at 14S in a sucrose gradient, and partition into the TX-114 aqueous phase. Fractions containing these high molecular weight proteins as well as fractions enriched in 88-kDa and 66-kDa polypeptides contain Mg(2+)-ATPase activities. Detergent-solubilized tubulins partition into the TX-114 aqueous phase, are not biotinylated, and must not be exposed to the ciliary surface. The detergent-insoluble axoneme and membrane fraction contains a 36-kDa polypeptide and a portion of the 50-kDa polypeptides that otherwise partition into the detergent phase. These polypeptides could not be solubilized by ATP or by NaCl extraction and appear to be associated with pieces of ciliary membrane tightly linked to the axoneme. The ciliary membrane polypeptides were also tested for Concanavalin A binding and at least sixteen Con A-binding polypeptides were resolved. Of the major Con A-binding polypeptides, three are hydrophobic and partition into the TX-114 detergent phase, three partition into the TX-114 aqueous phase, and four partition exclusively in the detergent-insoluble fraction, which contains axonemes and detergent-resistant membrane vesicles. PMID- 1640385 TI - Identification of Acanthamoeba at the generic and specific levels using the polymerase chain reaction. AB - We have adapted the polymerase chain reaction to identify strains of Acanthamoeba. Using computer-assisted analysis, primers were designed from an anonymous repetitive sequence and from published sequences of 18S and 5S ribosomal RNA genes of A. castellanii. Amplification of a short ribosomal DNA target (272 base pairs) at restrictive annealing conditions (greater than 50 degrees C) resulted in a single band that was unique for the genus and distinguished Acanthamoeba from Naegleria. This assay functioned with fresh and formalin-fixed cells as starting material. Amplification of longer targets (400 700 base pairs) at less restrictive annealing conditions (less than 47 degrees C) led to more than one band. This multiple banding pattern could reproducibly classify Acanthamoeba at the strain level and was, in certain cases, diagnostic for known pathogenic strains. However, these assays need to be further refined to make them relevant for clinical purposes. PMID- 1640386 TI - Characterization of the calcium-binding contractile protein centrin from Tetraselmis striata (Pleurastrophyceae). AB - Centrin is a major protein of the contractile striated flagellar roots of the green alga Tetraselmis striata. We present a newly modified procedure for the preparation of centrin in sufficient quantity and purity to allow for detailed biochemical characterization. We establish that centrin purified by differential solubility, followed by phenyl-Sepharose and DEAE-Sephacel chromatography is identical with the protein extracted directly from striated flagellar roots with regard to molecular weight, isoelectric point, and calcium-dependent behavior in SDS-PAGE. We also compare the biochemical properties of purified centrin with calmodulin isolated from Tetraselmis and calmodulin isolated from mammalian brain. Centrin can be fully distinguished from either algal or mammalian calmodulin on the basis of molecular weight, isoelectric point, calcium-dependent behavior in SDS-PAGE, proteolytic peptide maps, amino acid composition, ability to activate bovine brain phosphodiesterase, and reactivity with specific antibodies. PMID- 1640387 TI - Evidence of tyrosine kinase activity in the protozoan parasite Trypanosoma brucei. AB - Phosphorylation of proteins at tyrosine is an important mechanism for regulating cell growth and proliferation in metazoan organisms. In this report, we have demonstrated that Trypanosoma brucei, a protozoan parasite, possesses a tyrosine kinase that plays a role in regulation of proliferation of this protozoan. Genistein, a tyrosine kinase inhibitor, prevented multiplication of the parasite. An in vitro kinase assay demonstrated the presence of a kinase capable of phosphorylating an exogenous substrate at tyrosine, and genistein was able to reduce trypanosome-mediated phosphorylation of this substrate. An alkali digestion of 32P-labeled trypanosome proteins separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis indicated several proteins phosphorylated at tyrosine. These results indicate that T. brucei has a tyrosine kinase that is involved in proliferation or growth regulation of the parasite and provide further evidence for the possibility of growth factor regulation and signal transduction in trypanosomes. PMID- 1640388 TI - Characterization of the T, L, I, S, M and P cell surface (immobilization) antigens of Tetrahymena thermophila: molecular weights, isoforms, and cross reactivity of antisera. AB - In the ciliate protist Tetrahymena thermophila the L, H, T, I, S, M and P cell surface proteins (immobilization antigens) are expressed under different conditions of temperature (L, H, T), culture media (I, S), and mutant genotype (M, P). Immunoblot and autoradiographic studies using antisera to purified protein show that the molecular weights of these proteins range from 25,000 to 59,000. The H, T, S, M and P antigens are recognized as single polypeptides, whereas L, I, and one allelic form of T each appear to consist of a family of polypeptides. Although antisera are specific in immobilization and immunofluorescence assays of surface protein in living cells, cross-reactivity is seen with denatured protein on immunoblots. It is hypothesized that the surface protein genes are organized into families of evolutionarily related isoloci. PMID- 1640389 TI - Enhanced gametocyte formation in young erythrocytes by Plasmodium falciparum in vitro. AB - Two gametocyte-forming clones, HB-3 and 3D7, were used. Concentrates of late stage parasites were mixed with bloods containing different proportions of young erythrocytes, and the parasitemia and proportion of gametocytes determined after 2, 3 or 4 days of culture. Significantly more gametocytes were formed in light cells than in heavy cells separated from the same normal blood samples. Up to seven times more gametocytes were formed in reticulocyte-rich bloods from patients with sickle cell anemia than in normal control blood. PMID- 1640390 TI - The psychological treatment of patients with functional somatic symptoms: a practical guide. AB - Functional somatic symptoms (FSS) are bodily sensations which do not result from physical disease, but which the patient responds to as if they did. Such symptoms are common and usually transient. In some patients they become persistent and associated with distress and disability. In such cases specific treatment is indicated. A cognitive-behavioural model of the aetiology of FSS and a psychological treatment approach based on the model, are outlined. The practical details of treatment are described. PMID- 1640391 TI - Social relations, social support and survival among patients with cancer. AB - This study examined the relationship between social relationships and social support and survival following a first diagnosis of breast, colorectal, or lung cancer. Findings showed different factors related to survival for those with breast vs lung or colorectal cancer and for those with localized vs non-localized cancers. Results provide important evidence that social relations and social support may operate differently depending on cancer site and extent of disease. PMID- 1640392 TI - Power spectral analysis of heart rate variability in Type As during solo and competitive mental arithmetic task. AB - It has been reported that there are differences in autonomic balance between Type As and Type Bs. This study evaluated the sympathovagal interaction in Type A (N = 10) and Type B (N = 10) male students during mental arithmetic task in a solo and a competitive condition by the spectral component analysis of heart rate variability (HRV). The low-frequency (LF) component to high-frequency (HF) component ratio was significantly greater in Type As than in Type Bs, though no significant differences were found in task performance, heart rate change, and blood pressure between the two subject groups in both conditions. The present findings indicate that there was a significant difference in sympathovagal balance between Type As and Type Bs, and that Type As showed dominant sympathetic activity. The results suggest that the power spectral analysis of HRV, which is convenient and non-invasive, has enough sensitivity to discriminate differences in autonomic balance between Type A subjects and Type B subjects, not only during the solo and competitive task period but also during the resting period. PMID- 1640393 TI - Psychosocial adjustment following major gynaecological surgery for carcinoma of the cervix and vulva. AB - One-hundred and five women had undergone major gynaecological surgery for carcinoma of the cervix and vulva were interviewed retrospectively to elicit post operative psychosocial and psychosexual problems. This interview took place between 6 months and 5 yr after surgery. Responses to the Hospital Anxiety and Depression Scale indicated that 20% of the women were 'probable' cases of anxiety and 21% were 'definite' cases. On the depression scale, 18% were 'doubtful' cases and 14% were 'definite' cases. Scores on the scales were not associated with age of the woman, the type of operation or the time period between being interviewed and the operation. Two-thirds of the women who were sexually active prior to the operation indicated ongoing sexual problems when interviewed and the presence of these problems was found to be significantly associated with the woman's level of anxiety. PMID- 1640394 TI - The premenstrual syndrome: amelioration of symptoms after hysterectomy. AB - What is the role of the uterus in the aetiology of the premenstrual syndrome (PMS)? Twelve women kept a daily symptom record before and after hysterectomy. Psychological and physical symptom patterns were analysed by Fourier analysis and the response to hysterectomy by maximum likelihood ANOVA. Hysterectomy was associated with a 66% reduction in mean premenstrual tension (PMT) severity for both psychological and physical symptoms (p less than 0.005). The milder symptoms appeared unrelated to post-operative changes in health or ovarian function. Seven women experienced mood-related PMT in every pre-hysterectomy cycle; the persistence of unfailing mood-related PMT in one of these women after hysterectomy suggests that her symptoms were hormonally controlled and the loss of regular PMT in the other six women suggests that a uterine factor, or psychological factors associated with the menstrual cycle were implicated. We conclude that a uterus is not essential for the expression of PMT, but that its removal often results in the amelioration of symptoms. PMID- 1640395 TI - Psychopathology and pain in medical in-patients predict resource use during hospitalization but not rehospitalization. AB - The authors investigated the relationship between psychopathology and resource use in general medical in-patients during hospitalization and rehospitalization. Between 1 July 1987, and 30 April 1989, 1020 in-patients were prospectively screened for depression, anxiety, cognitive dysfunction, and pain. Overall, the screen identified 47% of patients as having high psychopathology or pain, including 25.7% depressed, 21.8% anxious, 17.6% with cognitive dysfunction, and 5.2% with high pain. There were no measured differences in demographics or disease severity between high and low psychopathology groups. High psychopathology patients had longer stays and higher costs during the index hospitalization but there were no differences during subsequent hospitalizations. Length of stay declined overall during the study period, but there were no changes over time in the association between high psychopathology or pain with increased resource use. The measured symptoms of psychopathology and pain we measured are associated with increased short-term utilization of health care resources, but the increase does not extend to subsequent hospitalizations. Outcome studies aiming to reduce psychopathology in medical in-patients should pay particular attention to short term costs. PMID- 1640396 TI - Measuring coping in breast cancer. AB - The emotional distress associated with breast cancer varies between individual women. These variations may be accounted for by differences in cognitive and behavioural coping responses to diagnosis. This study has attempted to develop a reliable, situation-specific approach to the measurement of coping responses in women with breast cancer. It has adapted a general coping questionnaire and modified an interview-based schedule for coping with cancer. The strengths and weaknesses of the interview and self-report methods of assessment are highlighted. Consistent results from these complementary approaches have been obtained. Both indicate the extensive use of cognitive avoidance and positive reappraisal. It has been shown that the majority of patients use a wide repertoire of coping responses which challenges the notion of mutually exclusive coping styles. These measures may be employed to examine the relationship between women's thoughts and behaviours in response to the diagnosis and treatment of breast cancer and subsequent psychological outcome. PMID- 1640397 TI - [Mediastinal extension of retropharyngeal abscess]. AB - Retropharyngeal abscesses in children are unusual and the involvement of the mediastinum is exceptional since the era of the antibiotics. It can be explained by the anatomic continuity between the retropharyngeal space and the retrooesophageal space. We report a case where the CT Scanner allows a complete evaluation of the disease in the mediastinum and a good follow-up. PMID- 1640398 TI - [Ileocolic intussusception in adults. Apropos of a case caused by benign inflammatory polyp of the terminal ileum]. AB - A case of an adult intussusception secondary to a fibroid polyp of the terminal ileum is reported. Adult intussusceptions are observed rarely, usually caused by an organic lesion. The preoperative diagnosis is based on US patterns, target aspect and sandwich sign. PMID- 1640399 TI - [Entrapped popliteal artery. Value of medical imaging and review of the literature]. AB - Medical imaging techniques (Duplex-scan, arteriography, CT scan, magnetic resonance) are obviously the most important elements in the diagnosis and prognostic evaluation in cases of "entrapped" popliteal artery. The physiopathogenic mechanism of this arteriopathy is a localized microtrauma of the arterial wall due to vascular compression by pre-existing anatomic abnormalities of the popliteal fossa. PMID- 1640400 TI - [Temporomandibular joint and rheumatoid polyarthritis. X-ray computed tomographic aspects]. AB - Direct coronal computed tomography (CT) examination of the temporomandibular joint (TMJ) was performed in 26 patients with rheumatoid arthritis (RA) and 26 control subjects. Changes in condylar shape, erosions and cysts of the mandibular condyle and condylar head resorption were more frequent among the RA group than the control group. Only the erosions and cysts of the mandibular condyle had a significantly higher frequency in the RA group than in the control group (p less than 0.05). Bone changes were bilateral in RA. Coronal view of the CT examination allow a clear visualization of the osseous elements of the TMJ but a control group is absolutely necessary to affirm with certainty the rheumatoid origin of the bone changes. The erosions and cysts of the mandibular condyle and their bilateral nature are the most specific features of RA on TMJ. PMID- 1640401 TI - [MRI and Sturge-Weber syndrome. Value of the injection of gadolinium. Apropos of a case]. PMID- 1640402 TI - [New elements in the recommendations of the International Commission for Radiological Protection]. PMID- 1640403 TI - [Radiodiagnosis at the University of California]. PMID- 1640404 TI - By-laws of the European Society of Uroradiology. Established August 26, 1990. PMID- 1640405 TI - The new immunology. AB - Among the biomedical sciences, immunology stands out as a discipline in which knowledge emanating from fundamental research has rapidly been transferred to the clinical paradigm, with consequent improvement in human health. Virtually all medical subspecialties have benefitted from diagnostic reagents and technologies provided by basic immunology. In terms of numbers of lives saved, immunologic based therapeutic strategies, most notably vaccination, rank among the most effective measures ever achieved by medical intervention. Yet, despite immunology's profound impact on medicine and the longstanding recognition of many of the general principles and cellular components involved in immunity, until relatively recently, the operational workings of the immune system eluded precise definition. The abstract nature of the immune system rendered the field intangible or, at the very least, confusing, to the nonimmunologic medical community. However, in recent years, this situation has changed radically, as cell cloning, hybridoma, and recombinant DNA technologies have provided the means to delineate the precise immunologic cellular structures and interactions. The purpose of this review is to highlight a few of the most significant advances in immunology during the past decade, and to show how they have made possible the translation of abstract concepts of classical immunology into tangible, structural information. Striking gains in the understanding of antigen recognition, one of the most fundamental aspects of immunity, are described as an illustrative case. PMID- 1640406 TI - Assessment of flap perfusion in a porcine model with a heated laser Doppler probe. AB - Skin and musculocutaneous flaps in a pig model were studied for their response to heating of the laser Doppler probe, both in the perfused state and in conditions of vascular occlusion. Even though heating the probe resulted in an elevation of perfusion of the flaps with no occlusions, it also increased the apparent perfusion of flaps that were occluded. The ability of flows to a augment with heating, therefore, could not be perfectly correlated with impeded vascular flow. The addition of a heated perfusion reading for assessment of vascular occlusion did not improve the accuracy of the laser Doppler for monitoring of capillary-bed perfusion to detect vascular occlusion. PMID- 1640407 TI - Health education works--at least for syphilis! PMID- 1640408 TI - Malignant melanomas masquerade--as benign naevi. PMID- 1640409 TI - Salt baths. PMID- 1640410 TI - Leptospirosis--a cause for concern? PMID- 1640411 TI - Leptospirosis--a cause for concern? PMID- 1640412 TI - Preferences in forms of address among female patients in military hospitals. PMID- 1640413 TI - Military cardiac rehabilitation. PMID- 1640414 TI - The smoking habits of young soldiers. AB - In a survey of the smoking habits of over 6,000 young soldiers, it was found that the prevalence of regular smoking was 45%. Though the prevalence of regular smoking in young soldiers is higher than the general prevalence rate for smoking in 16 to 19-year olds in the civilian population, the excess is considered to be a reflection of the social and geographical background of Army recruits. The survey found that young soldiers who smoke, smoke heavily. Eighty two percent smoked more than 20 cigarettes per week, 58% more than 40 cigarettes per week. This is higher than has been recorded by any previous survey of young soldiers. The proportion of young soldiers who have never smoked has risen markedly over the years. This survey found that 34% had never smoked. PMID- 1640415 TI - A survey of soldiers' attitudes to tattooing. AB - A study was performed at the Garrison Medical Centre, Larkhill to assess the incidence of skin tattoos in a sample of soldiers. The soldiers were questioned with the aim of establishing where they had had their tattoos done, identifying any factors involved in becoming tattooed and assessing what proportion later regretted their actions. The study included 450 male soldiers. Assessment was by a questionnaire completed in the medical centre waiting room. Overall 44% of the soldiers questioned were tattooed. Most (85.7%) had had tattoos done by recognised artists in the United Kingdom. Younger soldiers had a significantly higher incidence of 'home made' tattoos. Peer pressure was identified as an important influence on the decision to become tattooed. 31.1% of tattooed soldiers regretted their tattoos. This figure rose to 44.6% in those over 26 years old. The author advocates increased education to encourage the young soldier to think hard about its implications before becoming tattooed. PMID- 1640416 TI - An audiometric survey of territorial Army personnel. AB - A cross sectional survey of 581 TA personnel from Wales, the Midlands and Scotland was performed. The aim was to determine their hearing levels, to attempt to relate any degree of noise induced hearing loss detected with military, occupational and leisure noise and to make recommendations to improve the existing Army Hearing Conservation Programme. Each subject answered a questionnaire, had a clinical examination of each ear and pure tone audiometry. The hearing acuity of the TA group as a whole was similar to the regulars in the lower H gradings but there was a worrying number of H4/8 (5.6%) who had not been picked up before on routine screening and would probably have been discharged if they were in the Regular Army. PMID- 1640417 TI - British Army recruits: 100 years of heights and weights. AB - The heights and weights of Army recruits have been placed on record since 1860 in Reports of the Army Medical Department with certain gaps, particularly during the two World Wars and the period between them, until their publication was discontinued in 1975. Mean values corrected where necessary for minimum standards of height and weight--in order that the results should represent the civilian population from which they were drawn--are presented, showing the trends over a century. The Quetelet index w/h2, an indicator of weight corrected for height, is recommended as a measure of obesity for the Army. The value to the Army Medical Services of a continuously published record of heights and weights is assessed, and the hope is expressed that publication of these data will be recommenced. PMID- 1640418 TI - Post-operative wound infections in Belize. AB - The incidence of post-operative wound infections in Belize in 1986 and 1987 was studied. Both military practice in the military hospital and civilian practice in the rural hospitals of the local towns were included. Despite previous misgivings and sub-optimal conditions in the rural hospitals an acceptably low incidence was found in both areas of work. PMID- 1640419 TI - Management of respiratory complications after maxillofacial surgery on board ship. AB - An eight year old girl who probably inhaled gastric contents during surgery for cleft palate repair was ventilated for 10 days in the post-operative recovery area on board the Mercy Ship Anastasis with pulse oximetry as the only monitor of oxygenation. She walked off the ship on the seventeenth day. PMID- 1640420 TI - Tracheobronchomalacia. A rare cause of respiratory distress in children. AB - Tracheobronchomalacia is a rare cause of respiratory distress in children. An infant with tracheobronchomalacia is presented. The aetiology, pathophysiology and management are discussed. PMID- 1640421 TI - The genetics of type I (insulin dependent) diabetes mellitus. PMID- 1640422 TI - A submicroscopic translocation, t(4;10), responsible for recurrent Wolf Hirschhorn syndrome identified by allele loss and fluorescent in situ hybridisation. AB - A 2 year old girl presented with developmental delay and subtle dysmorphic features suggestive of Wolf-Hirschhorn syndrome (WHS). High resolution chromosome analysis was normal in the child and both parents. Molecular analysis indicated that the child had not inherited a maternal allele of probes from 4p16, confirming the clinical diagnosis. Prenatal diagnosis in the next pregnancy showed that again the fetus had no maternal allele for probes mapping to 4p16. Fluorescent in situ hybridisation in the mother showed a submicroscopic translocation, t(4;10). A normal karyotype in a child with clinical features of WHS is an indication for further investigation. PMID- 1640423 TI - Short stature in a girl with a terminal Xp deletion distal to DXYS15: localisation of a growth gene(s) in the pseudoautosomal region. AB - This report describes a Japanese girl with short stature and a rearranged X chromosome. Her height remained below the 3rd centile growth curve for Japanese girls, and her predicted adult height (148.5 cm) was below her target height (163 cm) and target range (155 to 171 cm). Cytogenetic studies showed that the rearranged X chromosome was formed by a breakage at q26 and a transfer of the Xq fragment onto the tip of Xp. The abnormal X was always late replicating. No mosaicism was detected. Molecular analysis showed an Xp terminal deletion distal to DXYS15. Biochemical and radiological studies for short stature disclosed no abnormality. On the basis of height analysis of previous reports and a genotype phenotype correlation of this patient, we propose that a growth gene(s) is present in the distal part of the pseudoautosomal region. PMID- 1640424 TI - Meiotic and sperm chromosome analysis in a male carrier of an inverted insertion (3;10)(q13.2;p14p13). AB - A phenotypically normal male who fathered a son with the karyotype 46,XY,del(10)(p13) was found to be a balanced carrier of an inverted insertion (3;10) (q13.2;p14p13). Karyotyping five later pregnancies showed four to be unbalanced with respect to the insertion, one of which was also trisomic for chromosome 18. The latest pregnancy was balanced with respect to insertion but had the additional complexity of 47,XXY. In the light of six out of six chromosomally abnormal pregnancies, two of which potentially exhibit an interchromosomal effect, it was decided to investigate the gametic output of the father. Testicular biopsy and semen samples were obtained permitting both meiotic and sperm chromosome analysis. Information was thus obtained at three levels of gamete production, that is, prophase I pairing, chiasma frequency distribution at metaphase I, and sperm karyotypes. Electron microscope studies of synaptonemal complexes showed the rearranged chromosomes to pair fully in meiotic prophase I with no indication of the presence of an insertion. This non-homologous pairing of the inserted region was accompanied by an abnormal frequency distribution of pachytene substages. There was also a reduction in chiasma frequency throughout the genome. However, this did not lead to detectable autosomal univalence or abnormally high X/Y univalence. Thus, the trisomy 18 and XXY pregnancies are unlikely to reflect increased non-disjunctional rates either before or during the first meiotic division. Sperm karyotyping showed that the proportion of chromosomally balanced:unbalanced gametes did not differ from the theoretically expected 1:1. There was no evidence of any increase of unrelated abnormalities in the sperm, further indicating that the overall rate of meiotic non-disjunction was not increased above normal. PMID- 1640425 TI - Linkage studies of four fibrillar collagen genes in three pedigrees with Larsen like syndrome. AB - We report seven children from three families who had a set of common clinical features suggestive of Larsen-like syndrome, including unusual facies, bilateral dislocations of the knees and elbows, club foot, and short stature. All of the patients originated from the island of La Reunion in the Indian Ocean. The occurrence of several affected sibs in these families and the large number of consanguineous marriages on this island are consistent with autosomal recessive inheritance of the disease. Based on this hypothesis, the pedigrees were used for linkage analysis in a candidate gene assay. Lod score calculations in a pairwise study with four different fibrillar collagen genes, COL1A1, COL1A2, COL3A1, and COL5A2, allowed us to exclude these genes as the mutant loci. Supporting this, electrophoretic analysis of collagens derived from fibroblast cultures failed to show defective molecules. We conclude that this syndrome is not a collagen disorder. PMID- 1640426 TI - A model to estimate the expression of the dystrophin gene in muscle from female Becker muscular dystrophy carriers. AB - The purpose of the present investigation was to assess the possibility of building a model to estimate, through dystrophin western blotting analysis, the expression of the DMD/BMD gene in muscle from heterozygotes. Dystrophin was analysed by mixing in increasing proportions (from 0% to 100%) aliquots of solubilised muscle from BMD patients with a qualitatively abnormal dystrophin and a normal male control. The intensity of the abnormal bands, which could be detected starting with 20% of muscle from the BMD patient, increased progressively according to the affected muscle concentration. In five obligate BMD carriers, two dystrophin bands were observed (corresponding to the products from the X bearing the normal and the BMD alleles), even among those with normal serum enzyme activities. Surprisingly, in the four obligate BMD carriers related to patients in whom an additional dystrophin fragment of 250 kd was present (two of them with raised serum enzymes), this band could not be seen, suggesting that the stability or the mechanism responsible for the synthesis of abnormal dystrophin products differs in heterozygotes compared to affected patients. PMID- 1640427 TI - Prevalence of congenital anomaly syndromes in a Spanish gypsy population. AB - We analysed the sample of gypsies included in the Spanish Collaborative Study of Congenital Malformations (ECEMC), a hospital based, case-control study and surveillance system. Special emphasis was placed on the birth prevalence of recessive multiple congenital anomaly syndromes, comparing their frequency in the gypsy population with that observed among non-gypsies. We observed an increased prevalence of birth defects, mostly because of groups of children with patterns of multiple anomalies and with autosomal recessive syndromes. The latter were approximately seven times more frequent in gypsies than in non-gypsies. We also estimated the carrier frequency in both groups (gypsy and non-gypsy). We consider that the frequent occurrence of the conditions observed reflects the high rate of consanguineous couples among the Spanish gypsy population. PMID- 1640428 TI - Echocardiography and genetic counselling in tuberous sclerosis. AB - OBJECTIVE: To assess echocardiography as an investigation for the detection of occult gene carriers in tuberous sclerosis. PATIENTS: Sixty parents of children with tuberous sclerosis who had been extensively investigated for signs of the disease and 60 age and sex matched controls. PROCEDURE: Blind study by two experienced echocardiographers and blind interpretation of video recordings by an adult cardiologist. SETTING: Cardiology department of a district general hospital. RESULTS: Two parents and three controls had bright echodense areas interpreted as possible rhabdomyomas. CONCLUSIONS: In our hands echocardiography of adults is not an investigation with a high specificity for gene detection in tuberous sclerosis. PMID- 1640430 TI - Charcot-Marie-Tooth (CMT) 1a duplication at 17p11.2 in Italian families. PMID- 1640429 TI - Attitudes towards prenatal diagnosis and carrier screening for cystic fibrosis among the parents of patients in a paediatric cystic fibrosis clinic. AB - The parents of all children attending the Royal Brompton National Heart and Lung Hospital cystic fibrosis paediatric clinic were asked to complete an anonymous postal questionnaire addressing attitudes towards prenatal diagnosis and population carrier screening for cystic fibrosis (CF); 65% (170/261) of parents responded. Of the respondents, 92% would support the introduction of a population screening test to detect carriers of CF and 19% felt such a test should be mandatory. A total of 64% of CF parents felt they would choose not to have any further children in the knowledge that they were both carriers, 74% would choose to have a prenatal test if they became pregnant, 44% would consider terminating an affected pregnancy, 33% would not, and 23% were unsure. Overall, 72% of respondents indicated they would choose to avoid having a further child with CF either by not having further children or by terminating an affected pregnancy. PMID- 1640431 TI - Spastic disorder in patients with hereditary multiple exostoses, but without spinal cord compression: a new syndrome? AB - We describe a 37 year old man with a history of a gait disorder which had been worsening over a period of three years. Clinical examination showed the typical signs of a spastic tetraparesis with increased tone of all the extremities. Sensation, autonomic and cerebellar functions were not disturbed. Multiple exostoses had been present since early childhood, but none had been found in the spine or the cranium to cause the tetraspastic disorder. MRI scan was normal. Pedigree analysis of four generations showed that other family members were affected by both disorders. Chromosomal analysis was normal. We consider this to be a previously unknown hereditary syndrome transmitted as an autosomal dominant and manifesting a combination of spastic tetraparesis and multiple exostoses. PMID- 1640433 TI - Three sibs with phalangeal anomalies, microcephaly, severe mental retardation, and neurological abnormalities. AB - This paper describes three children of a Pakistani first cousin marriage with a distinctive, non-progressive disorder characterised by variable phalangeal anomalies, microcephaly, pre- and postnatal growth retardation, poor vision, dystonic movements, a characteristic face, and severe mental retardation. This combination of features seems to be distinct and to represent a new autosomal recessive syndrome. PMID- 1640432 TI - Cerebrofaciothoracic dysplasia: a new family. AB - We describe two brothers, born to consanguineous parents, who had facial dysmorphism, complex anomalies of the vertebrae and ribs, enlarged cerebral ventricles and septum pellucidum, mental retardation, and affable behaviour. The features are similar to those previously described in three unrelated children and may represent new cases of cerebrofaciothoracic dysplasia. PMID- 1640434 TI - Necropsy findings in a fetus with a 46,XY,dic t(X;21)(p11.1;p11.1). AB - We report the findings in a fetus terminated because of multiple abnormalities diagnosed on ultrasound, including asymmetry of the limbs, a hypoplastic diaphragm, unilateral duplex kidney with a double ureter, unilateral cystic kidney, and congenital heart disease including total pulmonary atresia. Cytogenetic studies showed an unbalanced translocation of the long arm of the X chromosome to chromosome 21, resulting in a 46,XY,dic t(X;21)(p11.1;p11.1) karyotype. The cytogenetics were confirmed by non-isotopic in situ hybridisation using probes specific to pericentric alphoid repeats. Parental chromosomes were normal indicating this to be a de novo translocation. It is suggested that the inactivation of the long arm of the X chromosome has resulted in an effective monosomy for chromosome 21. PMID- 1640435 TI - Balanced translocation (14;20) in a mentally handicapped child with cystinuria. AB - A mentally handicapped 3 year old child with cystinuria is presented. Routine chromosomal analysis showed an apparently balanced de novo translocation in the child with breakpoints 14q22 and 20p13. Family studies suggested that the child is a type I/type II compound heterozygote for cystinuria. This translocation may indicate a possible locus for the gene for cystinuria. PMID- 1640436 TI - A terminal deletion of 11q. PMID- 1640437 TI - Trisomy 18 with karyotype 47,XX,-18,+i psu dic(18p). PMID- 1640438 TI - Chromosomes 14 and 21 as possible candidates for mapping the gene for Sanfilippo disease type IIIC. PMID- 1640439 TI - Prevalence of other birth defects among relatives of oral cleft probands. PMID- 1640440 TI - Microtia, absent patellae, short stature, micrognathia syndrome. PMID- 1640441 TI - Defining valve performance: importance and difficulties in testing heart valve replacement devices. AB - Defining and assessing the performance of heart valve replacement devices is difficult. This article is a brief discussion of the problems and present state of the art. PMID- 1640442 TI - In vitro evaluation of prosthetic heart valves: towards comparable testing. AB - The Laboratory of Biomedical Engineering (of the National Health Institute, technical body of the Italian Health Service) performs in vitro testing of prosthetic heart valves for mechanical characteristics of materials, fatigue life, and fluidodynamic performance. Testing of materials is directed towards the physicomechanical characterization of the structural components of the valves, e.g. elasticity and resistance to stress of biological tissues and stents. Long term fatigue life tests are conducted by means of systems which make valves beat at more than 1200 cycles/min. These tests are preceded and followed by geometrical characterization and by steady flow testing in order to obtain information about stenosis and leakage. Special attention is devoted to pulsatile flow testing which is performed on two pulse duplicators: the Dynatek system and the system developed by the University of Sheffield. The same valve was tested with these systems according to their different possible set-ups within the general requirements established by ISO-DIS 5840. This paper presents significant measurements, taking into account their dependence on the systems adopted. Results show (a) the difficulties in comparing test results because of different operating conditions, and (b) the systems' sensitivity with regards to some parameters which affect measurements under comparable set-up conditions (FDA Interlaboratory Comparison Testing Protocol). PMID- 1640443 TI - Clinical assessment of prosthetic valve function. AB - The advent of high-quality ultrasound technology has made the assessment of prosthetic valve function quicker, easier, and more accurate than ever before. By using cross-sectional imaging, colour flow mapping, and spectral Doppler techniques from both the precordium and the oesophagus, it is possible to assess a prosthetic valve fully. Cardiac catheterization with its attendant risks can be avoided. Echocardiography gives detailed morphological information, and it can be used for routine serial follow-up of individual patients. Using the patient as his or her own control avoids the problems caused by poorly-defined 'normal ranges' for prosthetic function. PMID- 1640444 TI - Understanding valve/host interactions through explanted valve analysis. AB - It is essential that the factors leading to bioprosthetic valve dysfunction are fully understood if a more durable bioprosthesis is to be developed and the incidence of premature failure reduced. Studies of explanted bioprostheses yield important information on both the aetiology of valve failure and influence of valve/host interactions. Details are given of the Sheffield Explant Study which holds data on 570 explants and 34 different models. Advantages and disadvantages of this type of study are discussed. PMID- 1640445 TI - A synthetic three-leaflet valve. AB - To increase durability and decrease calcification tendencies, the reduction of mechanical leaflet stress is of prime importance. In order to achieve this for a three-leaflet valve, the leaflets of a new design of prosthesis (the J-3) are manufactured in a medium open, almost flat shaped position, whereby the stent posts are expanded by a cone-shaped mold. Owing to this design, the leaflets have stable closed and open positions, the transition succeeds with low opening pressure. Valves are manufactured by dip-coating in polyurethane. Hydrodynamic evaluation of this polyurethane valve shows minimum pressure drop and very low energy losses compared with other commercially available valves. Very low shear stresses in the flow field downstream of the valve are observed by laser-Doppler anemometry. In durability tests, prototypes have reached lifetimes equivalent to 17 years. For comparative testing of durability and biocompatibility, six bioprostheses and seven J-3 valves were implanted in mitral position of growing Jersey calves. While animal tests are encouraging, they also reveal necessary manufacturing improvements. PMID- 1640446 TI - Issues surrounding the preservation of viable allograft heart valves. AB - Allograft heart valves have been used for over 30 years. During the first decades of use, the research and clinical objectives were to find a means for long-term storage of tissue. Methods such as irradiation, glutaraldehyde fixation, long term antibiotic storage at 4 degrees C and other methods were common. These methods, however, were found to give reduced long-term clinical performance when compared with viable fresh tissue or tissue which had been cryopreserved. Recognizing this fact, more recent emphasis has been to address issues surrounding means by which allografts can be cryopreserved and thawed to retain maximum viability. An additional concern was to find a means to maximize donor retrieval by salvaging tissue which normally would be discarded because of bacterial contamination. This study demonstrates that when a proper cryopreservation technique is used, with stringent antibiotic treatments, biomechanical parameters remain normal with only a slight decrease in cell viability. PMID- 1640447 TI - Valve data collection: problems and pitfalls. AB - Since 1981, the Department of Medical Physics and Clinical Engineering at the University of Sheffield has been responsible for the organization, management and data collection associated with the largest multicentre heart valve implant patient follow-up study in the Western world. At the present time, the database comprises information on over 16,000 valve implants, which have been provided by 57 surgeons working at 22 centres in the UK. All this data is available for in depth statistical analysis. Over 30 individual valve models presently are included in the Study and these can be categorized into five main types: ball, disc, porcine, pericardial and homograft. Analysis includes descriptive statistics as well as valuable information on the various performances of the different valves. Survival and event-free survival graphs are obtained by actuarial methods and individual valve types can be studied in depth in terms of freedom from thromboembolic complications and valve dysfunction. Whilst this approach provides interesting and valuable survival data, it does not take account of the wide variation in prognostic factors which occur within large groups of patients. This latter problem can be addressed by the use of proportional hazards analysis and this paper provides details of this approach and typical results obtained from the use of this method. These include the comparative performances of the major types of valves currently in use in terms of the event-free survival of the patients. PMID- 1640448 TI - Binding of proteins from embryonic and differentiated cells to a bidirectional promoter contained within a CpG island. AB - We have analysed binding sites of nuclear protein factors to a CpG island (HTF9), which contains the promoter for a pair of overlapping, divergently-transcribed "housekeeping" genes. Using DNaseI protection assays with extracts from a range of differentiated and undifferentiated cell lines, including mouse embryonic stem (ES) and embryonal carcinoma (EC) cells, we located multiple protein binding sites on HTF9. Most of the sites were outside the defined core promoter and could bind to previously identified transcription factors. These included constitutive, inducible and apparently tissue-specific factors in an extremely asymmetric array relative to the transcription start sites of the two genes. A number of sites showed different binding specificities or affinities in different cell types, including ES cells. However, we found no factors that were specific for both ES and EC cells, and no protein-binding site protected exclusively in undifferentiated embryonic cells. PMID- 1640449 TI - Eukaryotic initiation factor 3 does not prevent association through physical blockage of the ribosomal subunit-subunit interface. AB - The "native" 40 S ribosomal subunit, in which the protein eukaryotic initiation factor 3 is bound to the 40 S small ribosomal subunit, has been reconstructed to 48 A resolution. Comparison with a previous three-dimensional reconstruction of the "derived" 40 S subunit lacking any non-ribosomal components reveals the attachment site and morphology of the factor. It is a large (approximately 165 to 170 A long), bilobed, elongate structure, attached to the back lobes of the 40 S subunit by two strand-like features. Significantly, the factor is oriented away from the 60 S-subunit-40 S-subunit interface surface of the 40 S particle, suggesting that its anti-association activity is not accomplished via simple physical blockage of that surface. PMID- 1640450 TI - Kinking of RNA helices by bulged bases, and the structure of the human immunodeficiency virus transactivator response element. AB - We have used gel electrophoresis to show that the pyrimidine bulge of the HIV-1 TAR sequence causes a local bending of the helical axis. The TAR bulge caused a retardation in electrophoretic mobility in polyacrylamide gels. When this was placed adjacent to an additional bulged sequence in a linear RNA fragment, the mobility of the molecule varied sinusoidally with the spacing between the two bulges. Electrophoretic mobilities suggested that the TAR sequence context of the pyrimidine bulge causes a greater degree of axial kinking than in an equivalent randomly chosen sequence. Experiments in which an A5 bulge was progressively opposed by adenine bases inserted in the opposite strand showed that even a single opposed adenine markedly reduced electrophoretic mobility, i.e. axial bending, and two adenine bases reduced the mobility virtually to that of a normal duplex. We suggest that the pronounced kinking resulting from an unopposed bulge provides a particularly recognizable feature in RNA, and that this is the basis of the interaction between the HIV Tat protein and the TAR sequence. PMID- 1640451 TI - Formation of the right before the left mature DNA end during packaging-cleavage of bacteriophage T7 DNA concatemers. AB - During bacteriophage T7 morphogenesis in a T7-infected cell, mature length T7 DNA molecules join end-to-end to form concatemers that are subsequently both packaged in the T7 capsid and cut to mature size. In the present study, the kinetics of the appearance in vivo of the mature right and left T7 DNA ends have been analyzed. To perform this analysis, the intercalating dye proflavine is used to interrupt DNA packaging. When used at 0.5 to 8.0 micrograms/ml, proflavine progressively inhibits events in the T7 DNA packaging pathway, without either altering protein synthesis or degrading intracellular T7 DNA. Restriction endonuclease kinetic analysis reveals that proflavine (8 micrograms/ml) completely blocks formation of the mature T7 DNA left end, but only partially blocks formation of the mature T7 DNA right end. Both these and other observations are explained by the hypothesis that, in the T7 DNA packaging pathway, events occur in the following sequence: (1) formation of a mature right end; (2) packaging of at least some of the genome; (3) formation of the mature left end. PMID- 1640452 TI - Mutational substitution of residues implicated by crystal structure in binding the substrate glutathione to human glutathione S-transferase pi. AB - Site-directed substitution mutations were introduced into a cDNA expression vector (pUC120 pi) that encoded a human glutathione S-transferase pi isozyme to non-conservatively replace four residues (Tyr7, Arg13, Gln62 and Asp96). Our earlier X-ray crystallographic analysis implicated these residues in binding and/or chemically activating the substrate glutathione. Each substitution mutation decreased the specific activity of the enzyme to less than 2% of the wild-type. Glutathione-binding was also reduced; however, the Tyr7----Phe mutant still retained 27% of the wild-type capacity to bind glutathione, underlining the primary role that this residue is likely to play in chemically activating the glutathione molecule during catalysis. PMID- 1640453 TI - Effect of conformational features on the aminoacylation of tRNAs and consequences on the permutation of tRNA specificities. AB - The structure and function of in vitro transcribed tRNA(Asp) variants with inserted conformational features characteristic of yeast tRNA(Phe), such as the length of the variable region or the arrangement of the conserved residues in the D-loop, have been investigated. Although they exhibit significant conformational alterations as revealed by Pb2+ treatment, these variants are still efficiently aspartylated by yeast aspartyl-tRNA synthetase. Thus, this synthetase can accommodate a variety of tRNA conformers. In a second series of variants, the identity determinants of yeast tRNA(Phe) were transplanted into the previous structural variants of tRNA(Asp). The phenylalanine acceptance of these variants improves with increasing the number of structural characteristics of tRNA(Phe), suggesting that phenylalanyl-tRNA synthetase is sensitive to the conformational frame embedding the cognate identity nucleotides. These results contrast with the efficient transplantation of tRNA(Asp) identity elements into yeast tRNA(Phe). This indicates that synthetases respond differently to the detailed conformation of their tRNA substrates. Efficient aminoacylation is not only dependent on the presence of the set of identity nucleotides, but also on a precise conformation of the tRNA. PMID- 1640454 TI - Transcriptional commitment of mitochondrial RNA polymerase from Saccharomyces cerevisiae. AB - The transcriptional commitment of mitochondrial RNA (mtRNA) polymerase and the conditions required for the formation of a stable ternary complex have been determined by in vitro transcription study. Four different transcription complexes were made in vitro by incubating purified mtRNA polymerase, cloned synthetic mitochondrial promoters and selective ribonucleotides. The responses of these complexes to heparin, an inhibitor of unbound mtRNA polymerase, have been examined to determine their involvement in transcription. This study leads to the following observations. (1) Under normal reaction conditions, 40 nM-heparin completely inhibited mitochondrial transcription. (2) A preinitiation mitochondrial DNA-RNA polymerase complex (complex 0) showed partial resistance to heparin (approximately 25% resistant to 40 nm-heparin) when heparin and ribonucleoside triphosphates (rNTPs) were added together to the preformed complex. This complex was rapidly inactivated when preincubated with heparin before the addition of rNTPs. (3) The early initiation (complexes 2 and 4) containing DNA template, RNA polymerase and a short RNA product showed more resistance (approx. 40 to 50%) to 40 nM-heparin but destabilized upon further incubation with heparin before addition of the rest of the rNTPs. (4) After generation of ten or more phosphodiester bonds (complex 11), the early transcription complex is converted into a stable initiation complex, leading to the polymerase consignment to elongation. On the basis of stability and heparin sensitivity, three initial steps of mitochondrial transcription have been defined: polymerase-promoter interaction, initiation, and the transition from initiation to elongation. The formation of preinitiation complex is the rate limiting step t 1/2 approx. 50 s), whereas the initiation and elongation reactions are very fast processes (t 1/2 greater than 5 s) in mitochondrial transcription. PMID- 1640455 TI - Sequence-specific DNA binding by a two zinc-finger peptide from the Drosophila melanogaster Tramtrack protein. AB - We show that the DNA-binding domain of the Drosophila melanogaster regulatory protein Tramtrack consists of a 66 amino acid sequence containing two zinc-finger motifs and a short sequence N-terminal to the first finger motif. This short N terminal sequence is essential for DNA binding and we suggest it is involved in maintaining the three-dimensional structure of the first finger domain, as has been seen in the nuclear magnetic resonance structure of one of the zinc-finger domains of the yeast transcription factor SW15. The characterization of the DNA binding activity of this 66 residue peptide (delta 911zf) shows that it binds in a sequence-specific manner, as a monomer, to a natural target site with an apparent KD approximately 4 x 10(-7) M. The shortest delta 911zf binding site, which retains full affinity, consists of an 11 base-pair sequence with a one nucleotide overhang at each 5' end. DNase I, hydroxyl radical and methylation protection footprinting studies show that, in common with other zinc-finger proteins, delta 911zf binds in the major groove of DNA. The data presented are consistent with the zinc-fingers of Tramtrack contacting both strands of the DNA, and thus the binding differs in detail to that observed in the crystal structure of the three zinc-fingers of Zif268 complexed to their target DNA. PMID- 1640456 TI - Arginine regulon of Escherichia coli K-12. A study of repressor-operator interactions and of in vitro binding affinities versus in vivo repression. AB - The 12 genes which in E. coli K-12 constitute the arginine regulon are organized in nine transcriptional units all of which contain in their 5' non-coding region two 18 bp partially conserved imperfect palindromes (ARG boxes) which are the target sites for binding of the repressor, a hexameric protein. In vitro binding experiments with purified repressor (a gift from W. K. Maas) were performed on the operator sites of four genes, argA, argD, argF, argG, and of two operons, carAb and the bipolar argECBH cluster. A compilation of results obtained by DNase I and hydroxyl radical footprinting clearly indicates that in each case the repressor binds symmetrically to four helical turns covering adjacent pairs of boxes separated by 3 bp, but to one face of the DNA only. Methylation protection experiments bring to light major base contacts with four highly conserved G residues symmetrically distributed in four consecutive major grooves. Symmetrical contacts in the minor groove with A residues have also been identified. Stoichiometry experiments suggest that a single hexameric repressor molecule binds to a pair of adjacent ARG boxes. Although the wild-type operator consists of a pair of adjacent ARG boxes separated by 3 bp (except argR where there are only 2 bp), repressor can bind to a single box but with a greatly reduced affinity. Therefore, adjacent boxes behave co-operatively with respect to the Arg repressor binding, in the sense that the presence of one box largely stimulates the binding of the properly located second box. The optimal distance separating two boxes is 3 bp, but one bp more or less does not abolish this stimulation effect. However, it is completely abolished by the introduction of two or more additional bp unless a full helical turn is introduced. Large variations in the in vivo repression response between individual arginine genes or a wild-type gene and cognate Oc type mutants are not reflected by similar differences in the in vitro binding results where only small differences are observed. The significance of this lack of correlation is discussed. PMID- 1640457 TI - Binding of the arginine repressor of Escherichia coli K12 to its operator sites. AB - In the arginine regulon of Escherichia coli K12 each of the eight operator sites consists of two 18-base-pair-long palindromic sequences called ARG boxes. In the operator sites for the structural genes of the regulon the two ARG boxes are separated by three base-pairs, in the regulatory gene argR they are separated by two base-pairs. The hexameric arginine repressor, the product of argR, binds to the two ARG boxes in an operator in the presence of L-arginine. From the results of various kinds of in vitro footprinting experiments with the ARG boxes of argF and argR (DNase I protection, hydroxyl radical, ethylation and methylation interference, methylation protection) it can be concluded that: (1) the repressor binds simultaneously to two adjacent ARG boxes; (2) that it binds on one face of the double helix; and (3) that it forms contacts with the major and minor grooves of each ARG box, but not with the central three base-pairs. The repressor can bind also to a single ARG box, but its affinity is about 100-fold lower than for two ARG boxes. From gel retardation experiments with 3H-labeled repressor and 32P labeled argF operator DNA, it is concluded that the retarded DNA-protein complex contains no more than one repressor molecule per operator site and that most likely one hexamer binds to two ARG boxes. The bound repressor was shown to induce bending of argF operator DNA. The bending angle calculated from the results of gel retardation experiments is about 70 degrees and the bending center was located within the region encompassing the ARG boxes. The main features that distinguish the arginine repressor from other repressors studied in E. coli are its hexameric nature and the simultaneous binding of one hexameric molecule to two palindromic ARG boxes that are close to each other. PMID- 1640458 TI - Morphological pathway of flagellar assembly in Salmonella typhimurium. AB - The process of flagellar assembly was investigated in Salmonella typhimurium. Seven types of flagellar precursors produced by various flagellar mutants were purified by CsCl density gradient protocol. They were characterized morphologically by electron microscopy, and biochemically by two-dimensional gel electrophoresis. The MS ring is formed in the absence of any other flagellar components, including the switch complex and the putative export apparatus. Four proteins previously identified as rod components, FlgB, FlgC, FlgF, FlgG, and another protein, FliE, assemble co-operatively into a stable structure. The hook is formed in two distinct steps; formation of its proximal part and elongation. Proximal part formation occurs, but elongation does not occur, in the absence of the LP ring. FlgD is necessary for hook formation, but not for LP-ring formation. A revised pathway of flagellar assembly is proposed based on these and other results. PMID- 1640459 TI - Conformational switching in the flagellar filament of Salmonella typhimurium. AB - The flagellar filament of the mutant Salmonella typhimurium strain SJW814 is straight, and has a right-handed twist like the filament of SJW1655. Three dimensional reconstructions from electron micrographs of ice-embedded filaments reveal a flagellin subunit that has the same domain organization as that of SJW1655. Both show slight changes from the domain organization of the subunits from SJW1660, which possesses a straight, left-handed filament. This points to the possible role of changes in subunit conformation in the left-to-right-handed structural transition in filaments. Comparison of the left and right-handed filaments shows that the subunit's orientation and intersubunit bonding appear to change. The orientation of the subunit in the SJW814 filament is intermediate between that of SJW1655 and SJW1660. Its intermediate orientation may explain why the filaments of SJW1655 and SJW1660 are locked in one conformation, whereas the filament of SJW814 can be induced to switch by, for example, changes in pH and ionic strength. PMID- 1640460 TI - Three-dimensional structure of a cloning vector. X-ray diffraction studies of filamentous bacteriophage M13 at 7 A resolution. AB - Filamentous bacteriophage M13 is a single-stranded DNA phage about 65 A in diameter and 9300 A long. X-ray diffraction studies of magnetically oriented fibers of native, mercury and iodine-labeled phage particles have been used to determine the arrangement of the major coat protein, the gene 8 product, in the virion. The coat protein is made up of a single gently curving alpha-helix extending from approximately Pro6 to near the carboxyl terminus. The axis of the alpha-helix is tilted about 20 degrees from the viral axis and wraps around the axis in a right-handed helical sense. The surface of the virus is made up largely of polar residues in the amino-terminal half of the protein including the segment of alpha-helix extending from Pro6 to Tyr24. The interior surface of the protein coat faces the DNA and consists of an amphipathic helical segment extending from Thr36 to Ser50. The alpha-helices form a tightly packed 15 to 20 A thick cylindrical coat around the DNA. This structural model provides insight into the potential sites for incorporating foreign protein domains that may act as functional binding sites on the surface of M13. PMID- 1640461 TI - Determination of eukaryotic protein coding regions using neural networks and information theory. AB - Our previous work applied neural network techniques to the problem of discriminating open reading frame (ORF) sequences taken from introns versus exons. The method counted the codon frequencies in an ORF of a specified length, and then used this codon frequency representation of DNA fragments to train a neural net (essentially a Perceptron with a sigmoidal, or "soft step function", output) to perform this discrimination. After training, the network was then applied to a disjoint "predict" set of data to assess accuracy. The resulting accuracy in our previous work was 98.4%, exceeding accuracies reported in the literature at that time for other algorithms. Here, we report even higher accuracies stemming from calculations of mutual information (a correlation measure) of spatially separated codons in exons, and in introns. Significant mutual information exists in exons, but not in introns, between adjacent codons. This suggests that dicodon frequencies of adjacent codons are important for intron/exon discrimination. We report that accuracies obtained using a neural net trained on the frequency of dicodons is significantly higher at smaller fragment lengths than even our original results using codon frequencies, which were already higher than simple statistical methods that also used codon frequencies. We also report accuracies obtained from including codon and dicodon statistics in all six reading frames, i.e. the three frames on the original and complement strand. Inclusion of six-frame statistics increases the accuracy still further. We also compare these neural net results to a Bayesian statistical prediction method that assumes independent codon frequencies in each position. The performance of the Bayesian scheme is poorer than any of the neural based schemes, however many methods reported in the literature either explicitly, or implicitly, use this method. Specifically, Bayesian prediction schemes based on codon frequencies achieve 90.9% accuracy on 90 codon ORFs, while our best neural net scheme reaches 99.4% accuracy on 60 codon ORFs. "Accuracy" is defined as the average of the exon and intron sensitivities. Achievement of sufficiently high accuracies on short fragment lengths can be useful in providing a computational means of finding coding regions in unannotated DNA sequences such as those arising from the mega-base sequencing efforts of the Human Genome Project. We caution that the high accuracies reported here do not represent a complete solution to the problem of identifying exons in "raw" base sequences. The accuracies are considerably lower from exons of small length, although still higher than accuracies reported in the literature for other methods. Short exon lengths are not uncommon.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1640462 TI - Crystal structure of a berenil-d(CGCAAATTTGCG) complex. An example of drug-DNA recognition based on sequence-dependent structural features. AB - The AT-selective drug berenil has been co-crystallized with the dodecanucleotide sequence d(CGCAAATTTGCG)2. The crystal structure has been solved to a resolution of 2.0 A and an R factor of 18.3%, with the location of 65 water molecules. The drug is symmetrically bound in the 5'-AATT region of the minor groove, with its amidinium groups hydrogen-bonding to O-2 atoms of the thymine base at each end of the binding site. This arrangement is distinct from that previously found for berenil with the sequence d(CGCGAATTCGCG)2, which has the drug bound to the sequencing 5'-ATT via hydrogen bonds to adenine N-3 atoms with the involvement of a bridging water molecule at one end of the binding site. The reasons for these differences are discussed in terms of changes in helical parameters; in particular propeller twist and base-pair roll are considered to be important. The conformational and base-pair geometry of the dodecanucleotide in the structure reported here, is closely similar to that for the native structure, suggesting that the 5'-AAATTT sequence does not significantly alter during drug binding, either because of its inflexibility or because its geometry is nearly ideal for berenil binding. PMID- 1640463 TI - Accurate modeling of protein conformation by automatic segment matching. AB - Segment match modeling uses a data base of highly refined known protein X-ray structures to build an unknown target structure from its amino acid sequence and the atomic coordinates of a few of its atoms (generally only the C alpha atoms). The target structure is first broken into a set of short segments. The data base is then searched for matching segments, which are fitted onto the framework of the target structure. Three criteria are used for choosing a matching data base segment: amino acid sequence similarity, conformational similarity (atomic co ordinates), and compatibility with the target structure (van der Waals' interactions). The new method works surprisingly well: for eight test proteins ranging in size from 46 to 323 residues, the all-atom root-mean-square deviation of the modeled structures is between 0.93 A and 1.73 A (the average is 1.26 A). Deviations of this magnitude are comparable with those found for protein co ordinates before and after refinement against X-ray data or for co-ordinates of the same protein in different crystal packings. These results are insensitive to errors in the C alpha positions or to missing C alpha atoms: accurate models can be built with C alpha errors of up to 1 A or by using only half the C alpha atoms. The fit to the X-ray structures is improved significantly by building several independent models based on different random choices and then averaging co-ordinates; this novel concept has general implications for other modeling tasks. The segment match modeling method is fully automatic, yields a complete set of atomic co-ordinates without any human intervention and is efficient (14 s/residue on the Silicon Graphics 4D/25 Personal Iris workstation. PMID- 1640464 TI - Order-disorder phenomena in myelinated nerve sheaths. IV. The disordering effects of high levels of local anaesthetics on rat sciatic and optic nerves. AB - Sequences of 15 minute X-ray scattering spectra were recorded with rat sciatic and optic nerves, superfused with tetracaine-containing Ringer solutions. The spectra were analysed using the algorithm advocated in this series of papers. The main results, as a function of the time of exposure to tetracaine, were: the mean value of the repeat distance increases; its variance decreases; the average number of membrane pairs per coherent domain decreases; the fraction of isolated membrane pairs increases. Eventually, the spectra were observed to give way to the continuous intensity curve of a single, isolated membrane pair. At all stages of the experiment the continuous intensity curves were found to differ from one type of nerve to the other, and to be invariant, for each type of nerve, with respect to the tetracaine treatment. The X-ray scattering study clearly identified the nature of the structural differences between the two types of myelin sheaths: in that of native sciatic nerves, packing disorder preferentially affects the cytoplasmic space of the membrane pair, and tetracaine disrupts the packing in that space; in the myelin of optic nerves it is the external space that is preferentially affected by packing disorder and disrupted by tetracaine. The time-course of the structure parameters showed that, at any stage of the experiment, tetracaine acts preferentially on the more highly disordered regions of the structure and totally disrupts them. These results corroborate earlier conclusions reported in the previous papers of this series. An electron microscope study was also performed on tetracaine-treated nerves: the results, in close agreement with those of the X-ray scattering study, neatly confirm the conclusions given above. In a more general way, the remarkable agreement between the results of the analysis of the X-ray scattering spectra and the electron microscope observations strongly supports the validity of the physical model used in this series of papers and the correctness of the mathematical treatment that we advocate. Finally, the relations between this work and the work of others are discussed. It must be stressed that the present work bears on the toxic rather than on the anaesthetic effects of tetracaine. PMID- 1640465 TI - Nuclear magnetic resonance detection of bound water molecules in the active site of Lactobacillus casei dihydrofolate reductase in aqueous solution. AB - Proton nuclear magnetic resonance spectroscopy has been used to detect two water molecules bound to residues in the active site of the Lactobacillus casei dihydrofolate reductase (DHFR). Their presence was detected by measuring nuclear Overhauser effects between NH protons in protein residues and protons in the individual bound water molecules in two-dimensional nuclear Overhauser effect spectroscopy (NOESY), in nuclear Overhauser effect spectroscopy in the rotating frame (ROESY) and three-dimensional 1H-15N ROESY-heteronuclear multiple quantum coherence spectra recorded on samples containing appropriately 15N-labelled DHFR. For the DHFR-methotrexate-NADPH complex, two bound molecules were found, one close to the Trp5 amide NH proton and the other near to the Trp21 indole HE1 proton: these correspond to two of the water molecules (Wat201 and Wat253) detected in the crystal structure studies described by Bolin and co-workers. However, the nuclear magnetic resonance experiments did not detect any of the other bound water molecules observed in the X-ray studies. The nuclear magnetic resonance results indicate that the two bound water molecules that were detected have lifetimes in the solution state that are longer than approximately two nanoseconds. This is of considerable interest, since one of these water molecules (Wat253) has been implicated as the likely proton donor in the catalytic reduction of dihydrofolate to tetrahydrofolate. PMID- 1640466 TI - Purification and crystallization of human cathepsin D. AB - The two-chain form of human cathepsin D was purified from human spleen with a method utilizing an ion exchange chromatography step prior to the pepstatin affinity column normally used to purify aspartic proteases. The protein was crystallized from 21% polyethylene glycol 8000 at pH 4.0 using the hanging drop vapour diffusion method. Small crystals were used as seeds to grow crystals suitable for X-ray data collection. The crystals diffract to a resolution of 3.2 A and have space group P2(1)2(1)2(1) with unit cell dimensions a = 59.9 A, b = 99.6 A, c = 133.6 A. There are two molecules in the asymmetric unit. PMID- 1640467 TI - Crystallization of kappa-bungarotoxin: preliminary X-ray data obtained from the venom-derived protein. AB - kappa-Bungarotoxin is a 66 residue polypeptide found in the venom of the Taiwanese banded krait, Bungarus multicinctus. It binds tightly to neuronal nicotinic acetylcholine receptors and inhibits nerve transmission mediated by these postsynaptic receptors. It is related, by similarity in amino acid sequence, to alpha-bungarotoxin and other alpha-neurotoxins, but differs sharply in physiologic action. The alpha-neurotoxins inhibit nerve transmission in nicotinic acetylcholine receptors associated with vertebrate skeletal muscle and fish electric organs. The kappa-neurotoxins inhibit nerve transmission in neuronal nicotinic acetylcholine receptors such as those found in chick ciliary ganglia. The kappa-neurotoxins display a low level of interaction with receptors that are strongly affected by alpha-neurotoxins, but alpha-neurotoxins are completely without effect on receptors that are affected by kappa-bungarotoxin. The structural basis for this physiologic differentiation is not known. Crystals of kappa-bungarotoxin have now been obtained that diffract to at least 2.3 A. These crystals are hexagonal, space group P6, and have dimensions of a = b = 80.2 A, c = 39.6 A, and angles of alpha = beta = 90 degrees and gamma = 120 degrees. Each unit cell contains 12 molecules of the 66 residue protein or two molecules per asymmetric unit. Comparison of the structure of kappa-bungarotoxin, which will result from further diffraction analysis of these crystals, with the structures of the alpha-neurotoxins that have been determined may provide information on the structural basis of physiologic action in these acetylcholine receptor antagonists. PMID- 1640468 TI - Crystallographic data for the 9000 dalton wheat non-specific phospholipid transfer protein. AB - The wheat non-specific phospholipid transfer protein belongs to a family of small proteins sharing a common pattern of four disulphide bridges. Its function in vivo is not known, but it has a high affinity to phospholipids and is involved in phospholipid transfer in vitro. The molecular weight is 9607, and it crystallizes in the space group P2(1) with a = 40.73 A, b = 112.11 A, c = 50.44 A and beta = 106.80 degrees. The crystals diffract to 3 A resolution. PMID- 1640469 TI - Crystallization of the NAD-dependent malic enzyme from the parasitic nematode Ascaris suum. AB - The malic enzyme from muscle mitochondria of the parasitic nematode Ascaris suum is a tetramer of 65 kDa monomers that catalyzes the oxidative decarboxylation of malate to pyruvate and CO2 with NAD cofactor as oxidant. This malic enzyme is critical to the nematode for muscle function under anaerobic conditions. Unlike mammalian versions of the enzyme such as that found in rat liver, which require NADP as cofactor, the nematode version is an NAD-dependent enzyme. We report the crystallization of samples of the nematode enzyme at room temperature from pH 7.5 solutions of polyethylene glycol 4000 containing magnesium sulfate, NAD and sodium tartronate. Immediately upon mixing of protein and precipitant solutions, a marked precipitation of the protein occurs. Out of this precipitate, crystals appear almost immediately, most commonly in a truncated cube form that can grow to 0.5 to 0.7 mm on a cube edge in two to three days. The crystals are trigonal, space group P3(1)21 or its enantiomer, with a = b = 131.2(7) A, c = 152.6(9) A, and two monomers per asymmetric unit. Fresh crystals diffract X-radiation from a synchrotron source (lambda = 0.95 A) to about 3.0 A resolution. Rotational analysis of Patterson functions indicates that the malic enzyme tetramer has 222 symmetry. PMID- 1640470 TI - Factors influencing a woman's decision to end an extramarital sexual relationship. AB - While the role of individual characteristics has been examined for extramarital sexual involvement, the literature has yet to document personal factors associated with the termination of an affair. In doing so, this study examines the impact of a woman's sex role attributes ("masculinity") and attitudes toward sex (erotophobia-erotophilia) on her decision to terminate an extramarital affair. Masculinity was not related to affair length. The more positive a woman's attitude toward sex, the longer she continued the extramarital relationship. A further descriptive analysis suggests that this relationship may hold only for women in sexual affairs. The implications of these findings, methodological advances, and limitations of this study are discussed. Finally, recommendations for future research are explored. PMID- 1640471 TI - Infrequent orgasms in women. AB - Out of a sample of 2,425 gynecological patients aged 21-40 and married for at least one year, three groups were selected according to the frequency of coital orgasm. The first, orgastic, group contained 1,266 (52.2%) orgastic women, the second group included 466 (19.2%) patients with infrequent orgasms, and the third group consisted of 151 (6.2%) patients whose infrequent orgasms were felt by the examinees as distressing. Significant differences were found between the three groups concerning family environment and childhood, level of education and professional standing, sexual development and life, and in the incidence of psychopathological symptoms. It appears that the insufficient capacity of many women to attain regular orgasms in sexual intercourse is caused by several factors of both biological and psychosocial nature. PMID- 1640472 TI - It takes two to tango but one to infect (on the underestimation of the calculated risk for infection with HIV in sexual encounters, arising from nondisclosure of previous risk behavior or seropositivity). AB - The effects of nondisclosure of either HIV seropositivity or previous engagement in risk behavior on the estimation of risk in sexual intercourse is studied through the use of a probability model. Equations are utilized to derive an Underestimation Factor for three cases, which is shown to range from 2 to 20 in the case of insertive anal intercourse between an HIV+ and an HIV- man, and to 1 x 10(4) in a similar case of heterosexual insertive vaginal intercourse. This factor remains constant regardless of the number of sexual encounters between the same partners, and regardless of the protective measures as long as unawareness prevails. The discussion focuses on the implications of this formulation for education and social attitudes toward disclosure and nondisclosure in sexual encounters. It also raises the question of moral responsibility of sexual partners and some legal aspects of nondisclosure. PMID- 1640473 TI - Sexoanalysis: a new insight-oriented treatment approach for sexual disorders. AB - Sexoanalysis is an innovative therapeutic approach for the treatment of complex sexual disorders. This approach integrates current knowledge on sexual/erotic development pathology within a psychodynamic framework to help patients gain insight on the secondary gains, anxieties, and intrapsychic issues that are at the roots of their sexual problem. The treatment process essentially focuses on the analysis of sexual fantasies and the modification of maladaptive erotic imagery. The present authors present a brief overview of sexoanalytic theory and describe how sexoanalysis can resolve sexual disorders, improve sexual/erotic functioning, and promote sexual maturity. A clinical illustration is provided to help further clarify the sexoanalytic treatment process and demonstrate the use and utility of this promising sexotherapeutic approach. PMID- 1640474 TI - Brief report: recent findings on the Sexual Aversion Scale. AB - This study provides additional information on the psychometric properties of the Sexual Aversion Scale (SAS). Results suggest a positive relationship between sexual aversion, generalized anxiety, and history of sexual victimization. Variables such as age and religiosity were unrelated to scores on the SAS, although females reported significantly more sexual anxiety than males. The factor structure of the SAS is described and suggests that sexual aversion is a multifaceted problem with at least three and possibly four different dimensions. PMID- 1640475 TI - Sex therapy with dissociative disorders: a protocol. AB - Female victims of childhood sexual abuse who develop dissociative disorders often suffer from sexual dysfunction but do not receive sex therapy as often as might be expected due to the problems created by dissociative defenses. A modification of standard sex therapy techniques is proposed as a step toward restoring sexual function to this population. Key elements of the protocol are Eriksonian utilization of dissociative defenses, reduced expectations, and careful preparation of the male partner. PMID- 1640476 TI - Etiological attributions, responsibility attributions, and marital adjustment in erectile dysfunction patients. AB - The relationships between responsibility attributions, etiological attributions (psychogenically versus biogenically caused), and marital adjustment were explored in 30 erectile dysfunction patients and their partners via the Attributions Regarding Sexual Dysfunction Questionnaire and the Dyadic Adjustment Scale. Exploration of responsibility attributions yielded a consistent pattern of blaming the identified patient. This pattern is discussed in terms of two perspectives in attributional theory: the "self-serving bias" and the "just world" hypothesis. Etiological attributions were not relevant to actual diagnosis, marital adjustment, choice of treatment professional, or expectations for treatment outcome. Partner agreement regarding etiology was not related to actual cause or marital adjustment. PMID- 1640477 TI - Probing for prognostic markers at the cellular level: potentials and pitfalls. PMID- 1640478 TI - Crystallography getting attention on earth and in space. PMID- 1640479 TI - NASA and NIH sign research agreement. PMID- 1640480 TI - Nordic countries see rapid increase in melanoma. PMID- 1640481 TI - Sun-less tans may be possible with synthetic hormone. PMID- 1640482 TI - Antiproliferative and antitumor activity of the 2-cyanoaziridine compound imexon on tumor cell lines and fresh tumor cells in vitro. AB - BACKGROUND: Imexon, a 2-cyanoaziridine, is therapeutic and reverses lymphadenopathy and splenomegaly in the LP-BM5 murine retrovirus-induced immunodeficiency disease (murine AIDS). It can restore chemotherapy-induced immunosuppression. Imexon reduced the incidence of lymphoma in severe combined immune deficient mice inoculated with human lymphocytes. PURPOSE: To determine its antitumor activity, we screened imexon against fresh human tumor cells and tumor cell lines. To determine the time-concentration relationships of its cytotoxicity, we studied the effects of imexon on macromolecular synthesis and on the cell cycle. METHODS: Imexon was incubated at 1-200 micrograms/mL with various tumor cell lines, mitogen-stimulated peripheral blood lymphocytes, and fresh tumor cells. Cell survival, macromolecular synthesis, and cell cycle progression were studied. RESULTS: The concentration of imexon that caused 50% inhibition of growth was under 10 micrograms/mL for lymphocytes stimulated with mitogens. It was about 3-10 micrograms/mL for B-cell lymphomas and both multi-drug-resistant and -sensitive myeloma cell lines. Imexon inhibited four of seven fresh lymphoma and 11 of 16 fresh myeloma biopsy specimens to less than 40% of the control. A 1 hour exposure of lymphoma cells to 50-100 microgram/mL followed by removal of drug by washing the cells and continuing culture resulted in greater than 95% inhibition during the next 48-72 hours. Imexon selectively inhibited protein synthesis during the first 24-48 hours of exposure of lymphoma and myeloma cells. Cells exposed to inhibitory concentrations of imexon were blocked in cell cycle progression. CONCLUSION: Imexon may be a potentially useful agent in the treatment of malignant disease, particularly lymphoid malignancies, and should be explored further. PMID- 1640483 TI - Adjuvant radiotherapy and risk of contralateral breast cancer. AB - BACKGROUND: The risk of contralateral breast cancer is increased twofold to fivefold for breast cancer patients. A registry-based cohort study in Denmark suggested that radiation treatment of the first breast cancer might increase the risk for contralateral breast cancer among 10-year survivors. PURPOSE: Our goal was to assess the role of radiation in the development of contralateral breast cancer. METHODS: A nested case-control study was conducted in a cohort of 56,540 women in Denmark diagnosed with invasive breast cancer from 1943 through 1978. Case patients were 529 women who developed contralateral breast cancer 8 or more years after first diagnosis. Controls were women with breast cancer who did not develop contralateral breast cancer. One control was matched to each case patient on the basis of age, calendar year of initial breast cancer diagnosis, and survival time. Radiation dose to the contralateral breast was estimated for each patient on the basis of radiation measurements and abstracted treatment information. The anatomical position of each breast cancer was also abstracted from medical records. RESULTS: Radiotherapy had been administered to 82.4% of case patients and controls, and the mean radiation dose to the contralateral breast was estimated to be 2.51 Gy. Radiotherapy did not increase the overall risk of contralateral breast cancer (relative risk = 1.04; 95% confidence interval = 0.74-1.46), and there was no evidence that risk varied with radiation dose, time since exposure, or age at exposure. The second tumors in case patients were evenly distributed in the medial, lateral, and central portions of the breast, a finding that argues against a causal role of radiotherapy in tumorigenesis. CONCLUSIONS: The majority of women in our series were perimenopausal or postmenopausal (53% total versus 38% premenopausal and 9% of unknown status) and received radiotherapy at an age when the breast tissue appears least susceptible to the carcinogenic effects of radiation. Based on a dose of 2.51 Gy and estimates of radiation risk from other studies, a relative risk of only 1.18 would have been expected for a population of women exposed at an average age of 51 years. Thus, our data provide additional evidence that there is little if any risk of radiation-induced breast cancer associated with exposure of breast tissue to low-dose radiation (e.g., from mammographic x rays or adjuvant radiotherapy) in later life. PMID- 1640484 TI - Altered expression of the retinoblastoma gene product: prognostic indicator in bladder cancer. AB - BACKGROUND: It has been reported that 50%-70% of patients with bladder cancer experience recurrence after initial successful treatment and about 10%-20% of these patients die of the disease. Despite precise pathologic staging and grading, we are unable to predict clinical outcome in all patients. The retinoblastoma-susceptibility (RB) gene, a prototype of tumor suppressor genes, has recently been associated with development and/or progression of bladder cancer, as well as sarcoma and small-cell lung cancer. In transitional cell carcinomas of the bladder, we have observed altered expression of the Rb gene product--a nuclear phosphoprotein thought to function as a cell cycle regulator. PURPOSE: The aim of this study was to investigate the hypothesis that altered patterns of Rb expression correlate with prognosis in bladder cancer. METHODS: Expression of the RB gene was evaluated in specimens from 48 primary bladder tumors obtained by cystectomy or transurethral resection. Rb protein expression was correlated with disease outcome in these patients. Rb expression was examined by immunohistochemistry, using the mouse monoclonal antibody Rb-PMG3-245 on frozen tissue sections. Computerized image analysis was used to quantify the level of Rb protein in individual tumor cells. RESULTS: The overall 5-year disease-free survival was 66%, with a median follow-up of 42 months. Normal levels of Rb protein expression were found in 34 patients (Rb-positive group). A spectrum of altered patterns of expression from undetectable levels to heterogeneous expression, however, was observed in 14 patients (altered Rb group). Of the 38 patients with muscle-invasive tumors, 13 were categorized as having altered expression of Rb protein. Only one of 10 patients with superficial carcinomas had altered expression of Rb protein. The 5-year survival was significantly decreased in patients with altered Rb protein compared with the survival in patients with positive Rb expression (P less than .001). CONCLUSIONS: The results suggest that tumors exhibiting decreased expression of the RB gene coded product (Rb protein) had a more aggressive biological behavior than those that expressed the Rb protein in the majority of their tumor cells. IMPLICATIONS: This study demonstrates that altered patterns of Rb protein expression may be an important prognostic variable in patients presenting with invasive bladder cancer. PMID- 1640485 TI - Altered expression of retinoblastoma protein and known prognostic variables in locally advanced bladder cancer. AB - BACKGROUND: The clinical behavior of the tumor in patients with locally advanced bladder carcinoma is unpredictable. Current predictors of clinical behavior include depth of muscle invasion, presence of vascular invasion, proliferation rate, and loss of blood group antigens. Treatment selection would be facilitated by the development of a reliable marker of tumor progression. Functional retinoblastoma (RB) gene loss has been reported to occur in bladder carcinoma, but the significance of this loss is unknown. PURPOSE: We have evaluated the frequency of functional loss of the RB gene in locally advanced bladder carcinoma and have compared the results to known prognostic factors in the same cohort. METHODS: Forty-three study patients with pathologically well-characterized, locally advanced bladder carcinoma, who were placed in a protocol incorporating surgery and chemotherapy, were studied for known clinical and pathological prognostic indicators as well as for their Rb status. Formalin-fixed and paraffin embedded archival primary tumor tissues were used for histological and immunohistochemical analyses. RESULTS: Altered Rb protein expression was documented in 37% of the tumor specimens. The high rate of altered Rb expression found in this cohort with advanced urothelial tumors strongly suggests that RB functional loss may be associated with tumor progression in this malignancy. Altered Rb protein expression was found to be independent of other known prognostic variables. A significantly poorer tumor-free survival rate also was noted for those patients who had a tumor with an altered Rb protein with or without vascular invasion. CONCLUSION: The high frequency of Rb alteration in locally advanced bladder carcinomas, plus the fact that a significant correlation could not be found between the Rb status and other known prognostic markers in this preliminary study, suggests that altered RB expression may be an independent prognostic marker of tumor progression in bladder cancer. PMID- 1640486 TI - Cigarette smoking and other risk factors for progression of precancerous stomach lesions. AB - BACKGROUND: Stomach cancer is generally thought to evolve through a series of gastric mucosal changes, but the determinants of the precancerous lesions are not well understood. PURPOSE: Our purpose was to assess risk factors for intestinal metaplasia and gastric dysplasia arising from chronic atrophic gastritis in a general population at high risk for stomach cancer. METHODS: A population-based gastroscopic screening of more than 3000 residents was conducted in a county in China with one of the world's highest rates of stomach cancer. Information on the lifestyle and other characteristics of the participants was obtained by interview, and responses were compared between those in whom the most advanced gastric lesion was dysplasia or intestinal metaplasia versus those with chronic atrophic gastritis. RESULTS: Cigarette smoking was found to nearly double the risk of transition to dysplasia and to be a mild risk factor for intestinal metaplasia. Smoking accounted almost entirely for the 55% higher prevalence of dysplasia among men than among women. Risk of transition to dysplasia had a weak association with several dietary factors and was increased among those participants with a family history of stomach cancer and with blood type A. CONCLUSIONS: The findings provide strong evidence for a role of tobacco consumption and offer clues to other environmental and genetic factors involved in the process of gastric carcinogenesis. PMID- 1640487 TI - Multiparametric prognostic evaluation of biological factors in primary breast cancer. AB - BACKGROUND: An array of biological features related to tumor cell differentiation status, growth rate, and invasive potential have been identified as potential prognostic factors in breast cancer. We were interested in determining their relative importance in predicting patient survival. PURPOSE: We evaluated the relative weight of the following four biological factors in predicting survival of patients with breast cancer: tumor cell DNA content (determined by flow cytometry), tumor cell proliferation rate (determined by thymidine kinase activity), expression levels of cathepsin D and urokinase plasminogen activator, and several "classical" clinical and histological factors. METHODS: Selected from a prospectively updated database, the study population consisted of 319 primary breast cancer patients who received treatment and follow-up care (median, 6 years) in the Centre Rene Huguenin. To determine the profile of biological factors for each patient, we used frozen tumor specimens and (except for the flow cytometric DNA content assay) commercially available assay kits. We determined by Cox multivariate analysis the relationships of the biological factors to each other, to classical prognostic factors, and to disease-free and metastasis-free survival. RESULTS: In the overall population, disease-free survival was best predicted by node status (P = .004), clinical tumor size (P = .02), and cathepsin D expression (P = .01), whereas metastasis-free survival was best predicted by node status (P = .0004), clinical tumor size (P = .009), and urokinase plasminogen activator expression (P = .04). In node-negative patients, thymidine kinase activity was the only factor selected for disease-free (P = .04) and metastasis-free (P = .05) survival. In node-positive patients, the number of positive axillary lymph nodes was the only factor selected for disease-free (P = .0008) and metastasis-free (P = .00017) survival. CONCLUSIONS: Our retrospective analysis has identified protease expression and tumor cell proliferation rate as important biological prognostic factors in breast cancer. Prospective clinical trials should be undertaken to confirm these results. PMID- 1640488 TI - Evaluation of in vivo breast fine needle aspirates by flow cytometry: an efficacy study. AB - BACKGROUND: Malignancy of the breast is frequently diagnosed through fine needle aspiration. In the hands of a skilled aspirator and cytopathologist, this can be a highly accurate procedure. PURPOSE: This study was undertaken to evaluate whether sufficient residual cells in the bore of the needle could be harvested and analyzed efficiently by flow cytometry analysis. The goal was then to determine the value of routine flow cytometry as an adjunctive technology in the interpretation of breast fine needle aspirations. METHODS: Cells were rinsed from the needles of 83 consecutive diagnostic fine needle aspirates after preliminary inspection had confirmed adequate material was obtained for cytopathology. Cells were washed, and nuclei prepared by detergent treatment. After ribonuclease treatment, DNA was stained with the fluorescent marker propidium iodide. DNA content per cell was determined by flow cytometry by measurement of right-angle fluorescence. RESULTS: Less than 4% of the samples were rejected for inadequate cell numbers. Flow cytometry criteria for evidence of malignancy included the presence of a DNA aneuploid population or an elevated rate of proliferation (13% or higher) of a diploid population. Accuracy of flow cytometry was based on cytopathologic interpretation in all cases except two which were based on results of excisional biopsy. The sensitivity of the flow cytometry analysis was 76%; the specificity was 100%, with results from flow cytometry pivotal in the correct diagnoses for two patients whose cytopathologic results were equivocal. Analysis of histograms indicated acceptable coefficients of variation for all populations. Gating analysis indicated the suitability of the material for this type of study, with an average of 85% of the events selected, or "gated in." Low recoveries were associated with the presence of necrotic debris in the sample. CONCLUSION: Flow cytometry can be a valuable adjunctive technology, capable of providing the cytopathologist with additional information regarding the character of cells analyzed. PMID- 1640489 TI - Incidence of non-Hodgkin's lymphomas in Italy. Working Group on the Epidemiology of Hematolymphopoietic Malignancies in Italy. PMID- 1640490 TI - Antineoplastic drug screening. PMID- 1640491 TI - BNCT: looking for a few good molecules. PMID- 1640492 TI - Axonal regeneration of an identified Helisoma neuron depends on the site of axotomy. AB - Axotomy of molluscan neurons usually results in axonal regeneration. In this study, we tested the axotomy response of an identified neuron of the pond snail Helisoma trivolvis (buccal neuron 4, B4). This neuron has two primary axonal branches, the ipsilateral axon and the contralateral axon, each innervating one of the paired salivary glands. The ipsilateral axon projects via the ipsilateral esophageal nerve trunk whereas the contralateral axon crosses both buccal ganglia and projects via the contralateral esophageal nerve trunk. We tested various procedures of axotomy: injury to one axon or both axons, close to the ganglion or more distal. Surprisingly, we found that proximal axotomy of the ipsilateral axon was not usually followed by axonal regeneration. By contrast, all other procedures of axotomy (e.g., distal ipsilateral, or proximal bilateral) resulted in robust axonal regeneration and target reinnervation. Thus, in this preparation, axotomy may or may not result in axonal regeneration, depending on the site(s) of axotomy. To the best of our knowledge, such a differential result has not yet been found in any other preparation. We conclude that axotomy is not always a sufficient condition for axonal regeneration of molluscan neurons. We hypothesize that a damaged axonal stump may be a necessary condition for the initiation of regeneration. An alternative hypothesis is that neurite outgrowth is inhibited in normal mature neurons by a target-derived factor. This hypothetical factor would be transported retrogradely, but not anterogradely, along axons. PMID- 1640493 TI - Common sequence on distinct V beta genes defines a protective idiotope in experimental encephalomyelitis. AB - Synthetic TCR peptides expressed by encephalitogenic T cells can induce both cellular and humoral responses that protect against experimental encephalomyelitis. In the Lewis rat, encephalitogenic T cells predominantly express V beta 8.2, and a peptide in the CDR2 region representing residues 39-59 could both protect against and treat experimental autoimmune encephalitis (EAE). Similarly, the homologous and cross reactive 39-59 peptide from V beta 8.6 expressed by an EAE-protective clone also had protective and therapeutic activity against EAE. The consensus sequence between the V beta 8.2 and V beta 8.6 peptides, which included residues 44-54, was postulated to contain the protective idiotope. In this report, we demonstrate that this peptide, designated V beta 8 44-54, has comparable activity to the longer peptides for treating both active and passive EAE. Similar to the longer V beta 8.2-39-59 peptide, the V beta 8-44 54 peptide stimulates protective TCR peptide-specific CD4+, CD8dim T cells restricted by MHC I. We also report for the first time the recovery of V beta 8 44-54 reactive T cells that express a variety of V beta genes in their T-cell receptor (TCR), including V beta 4, 8, 10, 12, 15, 17, 19, and 20. Taken together, these data establish that the V beta 8-44-54 sequence constitutes an important autoregulatory idiotope in EAE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640494 TI - Transferrin receptor expression in myelin deficient (md) rats. AB - The question of iron regulation in the brain is the subject of increasing interest as the evidence continues to accumulate that a loss of brain iron homeostasis plays a significant role in some neurodegenerative diseases. Most cells acquire iron through a specific receptor mediated process involving transferrin, the iron mobilization protein. It appears that in the brain, endothelial cells, neurons, and oligodendrocytes express the transferrin receptor. This study uses a strain of rats (myelin deficient, md) in which oligodendrocytes fail to mature, and examines the consequences of this genetic defect on the expression of the transferrin receptor in the brain. The affinity of transferrin for its receptor is similar between the cerebral cortex and cerebellum in both the normal and myelin deficient rats (Kd = 7.8-10.6 nM). The transferrin receptor density is normally 2-3 times higher in the cerebellum than in the cerebral cortex. In the myelin deficient rat strain, the density of the transferrin receptor is decreased in both the cerebrum (56%) and cerebellum (70%) compared to the littermate control animals. Because oligodendrocytes are the only cell type affected in this mutant, the results suggest that these cells are responsible for a considerable amount of the transferrin receptors that are expressed in the brain (excluding the endothelial cell contributions). These observations are consistent with the existing literature stating that oligodendrocytes are responsible for the majority of transferrin and transferrin mRNA which is expressed in the brain, and support the working hypothesis that imbalances in brain iron homeostasis, particularly during development, are associated with myelin disorders. PMID- 1640495 TI - Immunohistochemical localization of beta-amyloid precursor protein sequences in Alzheimer and normal brain tissue by light and electron microscopy. AB - Immunohistochemical staining with antibodies directed against four segments of the amyloid precursor protein (APP) was studied by light and electron microscopy in normal and Alzheimer (AD) brain tissue. The segments according to the Kang et al. sequence were: 18-38 (T97); 527-540 (R36); 597-620 (1-24 of beta-amyloid protein [BAP], R17); and 681-695 (R37) (Kang et al. [1987]: Nature 325:733-736). The antibodies recognized full length APP in Western blots of extracts of APP transfected cells. They stained cytoplasmic granules in some pyramidal neurons in normal appearing tissue from control and AD cases. In AD affected tissue, the antibodies to amino terminal sections of APP stained tangled neurons and neuropil threads, and intensely stained dystrophic neurites in senile plaques. By electron microscopy, this staining was localized to abnormal filaments. The antibody to the carboxy terminal segment failed to stain neurofibrillary tangles or neuropil threads; it did stain some neurites with globular swellings. It also stained globular and elongated deposits in senile plaque areas. The antibody against the BAP intensely stained extracellular material in senile plaques and diffuse deposits. By electron microscopy, the antibodies all stained intramicroglial deposits. Some of the extracellular and intracellular BAP-positive deposits were fibrillary. Communication between intramicroglial and extracellular fibrils was detected in plaque areas. These data suggest the following sequence of events. APP is normally concentrated in intraneuronal granules. In AD, it accumulates in damaged neuronal fibers. The amino terminal portion binds to abnormal neurofilaments. Major fragments of APP are phagocytosed and processed by microglia with the BAP portion being preserved. The preserved BAP is then extruded and accumulates in extracellular tissue. PMID- 1640496 TI - Reactive microglia/macrophages phagocytose amyloid precursor protein produced by neurons following neural damage. AB - Kainic acid lesions of rat striatum caused an elevation of amyloid precursor protein (APP) immunoreactivity in neurons and neurites, some of which were then phagocytosed by reactive microglia/macrophages. Immunoexpression of APP was observed in neurites and neurons 1 day after the kainic injection. Four days after lesioning, immunoreactivity was still concentrated in thick and distorted neurites, but it began to appear in microglia/macrophages and in the tissue matrix. The cells were identified as microglia/macrophages by the phenotypic markers Ia (OX6), leukocyte common antigen (OX1), C3bi receptor (OX42), and macrophage marker (ED1). They were negative for the astrocytic marker glial fibrillary acidic protein (GFAP). APP immunoreactivity in these phagocytic cells was most prominent between 1 week and 1 month postlesioning. No extracellular amyloid fibrils were detectable. These results suggest that APP production is rapidly upregulated in damaged neurons and accumulates in degenerating axons. However, phagocytosis of APP by reactive microglia/macrophages in this rat model does not result in production of Alzheimer type amyloid deposits. PMID- 1640497 TI - Substratum-induced modulation of acetylcholinesterase activity in cultured dorsal root ganglion neurons. AB - Acetylcholinesterase (AChE) has been shown to be transiently expressed in the developing nervous system during periods of neuronal migration and axonal outgrowth. We are investigating the possible interaction of substratum with AChE activity in dorsal root ganglion neurons (DRGN) cultured on substrata with varying degrees of permissiveness for neurite outgrowth: (1) extracellular matrix substrata: reconstituted basal lamina Matrigel (MGEL), laminin (LAM) and type I collagen (COL), and (2) organotypic substrata: unfixed, frozen sections of sciatic nerve (SN) and spinal cord (SC). In group 1, histochemical staining for AChE in DRGN was lowest on MGEL where outgrowth was most vigorous, intermediate on LAM, and highest on COL where neurite outgrowth was reduced by 55% compared to Matrigel and highly fasciculated. A similar trend was seen when the cultures were assayed biochemically, 2.84 +/- 0.14 nmoles ACh hydrolyzed/ganglion/hr (MGEL), 4.42 +/- 0.19 (LAM), 5.79 +/- 0.37 (COL). In group 2, SN supported an expansive outgrowth with lower AChE activity than in DRGN grown on SC where outgrowth was minimal. These studies show that the levels of AChE activity can be modulated by substratum, perhaps in proportion to the permissiveness of the substratum to neuritic outgrowth. These results are discussed in relation to possible non cholinergic roles of AChE. PMID- 1640498 TI - Effects of protein kinase inhibitors on regeneration in vitro of adult frog sciatic sensory axons. AB - The effects of protein kinase inhibitors on regeneration in vitro of adult frog sciatic sensory axons were tested. Regeneration of crush-injured nerves for 8 days in serum-free medium was inhibited by staurosporine (100 nM) and H-7 (100 microM), which are both known to inhibit protein kinase C. With the use of a compartmented culture system it could be shown that H-7 exerted both local (outgrowth region) and central (ganglia) effects, the latter being more pronounced. The local effects could be due to reduction of Schwann cell proliferation by H-7. Immunohistochemistry demonstrated the presence of protein kinase C in neuronal cell bodies but not in axonal processes. Proliferation of Schwann cells was accompanied by increased protein kinase C immunoreactivity at the site of injury. H-7 caused a selective inhibition in the incorporation of radioactive phosphate into one 74 kDa protein of both ganglia and nerve but also a more general decrease in protein labelling. The results show that protein phosphorylations, possibly mediated by protein kinase C, are involved in regeneration-related mechanisms operating at both local and central levels in the adult frog sciatic sensory axons. PMID- 1640500 TI - Focal, extracellular recording of slow miniature junctional potentials at the mouse neuromuscular junction. AB - Miniature endplate potentials (MEPPs) with slow rising phase can be attributed either to burst of transmitter releases or to distortion of conduction from remote releasing sites. The spontaneous activity of neuromuscular junctions recorded extracellularly at mouse diaphragms using sharp electrodes was analyzed to test these two hypotheses. The miniature junctional potentials (MEJPs) frequencies observed intracellularly as compared to MEPP frequency measured intracellularly in controls indicate that most events recorded extracellularly are induced by the presence of the electrode. All types of MEPPs (bell-MEPPs, skew-MEPPs, slow-, and giant MEPPs) previously described with intracellular recording methods (Vautrin and Kriebel, Neuroscience 41:71-88, 1991) were observed extracellularly and showed similar characteristics. This means that the presynaptic and postsynaptic zones that generate these synaptic events are restricted within areas of a few micrometers squared of synaptic contact. Long rise times of extracellularly recorded synaptic spontaneous events may be explained by multiple transmitter releases at intervals shorter than the rise time of individual events, which postsynaptic responses fuse into a single peak. PMID- 1640499 TI - Expression of multiple integrins and extracellular matrix components by C6 glioma cells. AB - We have investigated the expression of integrins in C6 glioma, a chemically induced glial tumor cell line from rat brain. Immunochemical analysis revealed that C6 cells express sets of integrin receptor complexes which immunologically and electrophoretically are indistinguishable from those expressed by normal rat skin fibroblasts. These include the well-characterized fibronectin (alpha 5 beta 1) and the multi-specific laminin, collagen and fibronectin (alpha 3 beta 1) receptors. Assay of cell adhesion indicated that C6 cells adhere to fibronectin coated surfaces or matrix deposited by the C6 glioma cells (CGM) in an RGD- and divalent cation-dependent fashion. However, anti-fibronectin antibodies, which are able to inhibit fibroblast adhesion to fibronectin, did not inhibit adhesion of the C6 cells to fibronectin or CGM. This may reflect differences in functional properties and/or distribution patterns of integrins in C6 cells and normal fibroblasts. PMID- 1640501 TI - Alterations of 45Ca accumulation and [3H]inositol 1,4,5-trisphosphate binding using autoradiography in the exo-focal postischemic brain areas of the rat. AB - We studied the alterations of calcium accumulation and intracellular signal transduction using autoradiography of the second messenger system in order to clarify the mechanisms of the delayed neuronal changes in the remote areas of rat brain after transient focal ischemia. Chronological changes of 45Ca accumulation and [3H]inositol 1,4,5-trisphosphate (IP3) binding sites were determined after 90 min of right middle cerebral artery (MCA) occlusion and after such occlusion followed by different periods of recirculation. After the ischemic insult, 45Ca accumulation extended to the lateral segment of the caudate putamen and to the cerebral cortex, both supplied by the occluded MCA. One day after the ischemia, [3H]IP3 binding sites decreased significantly compared with the control values in these ischemic areas. Moreover, 3 days after the ischemia, 45Ca accumulation was first detected in the ipsilateral thalamus and the substantia nigra, which lay outside the ischemic areas. In the substantia nigra, a significant decrease of [3H]IP3 binding sites and concurrent 45Ca accumulation were observed. In the thalamus, however, there was not alteration until 1 week after the ischemia, and then [3H]IP3 binding sites increased significantly 2 weeks (P less than 0.05) and 4 weeks (P less than 0.01) after the ischemia. Based on the present study, we speculate that different mechanisms associated with signal transduction systems may be responsible for exo-focal postischemic delayed neuronal changes in the thalamus and the substantia nigra. The increase of [3H]IP3 binding sites of the thalamus in the chronic stage may be new evidence of plasticity related to neurotransmission. PMID- 1640502 TI - Hippocampal NCAM180 transiently increases sialylation during the acquisition and consolidation of a passive avoidance response in the adult rat. AB - Synaptic connectivity change is a consistent anatomical feature of memory formation and the possibility that this is mediated by a replay of neurodevelopmental events has been investigated by measuring change in neural cell adhesion molecule sialylation state during the acquisition and consolidation of a passive avoidance response in the adult rat. The avoidance response was always generated after two to three trials and the animals remained on the platform for the criterion time of 5 min. In all cases training was complete within 5-8 min. Change in sialylation state was monitored following intraventricular infusion of the 3H-ManNAc precursor at 4 hr prior to the reference point. No task-specific change in general glycoconjugate sialylation was apparent in hippocampal P2 pellets at increasing times following training. Increased sialylation state was observed only in neural cell adhesion molecule (NCAM) immunoprecipitates of hippocampal membrane fractions at 12 and 24 hr after training. Change in hippocampal sialylation state could not be attributed to an increased accumulation of NCAM as detected by an immunoabsorbent assay. Immunoblotting of antibody precipitated NCAM demonstrated the 3H-ManNAc to be incorporated into the synapse-specific, 180 kDa isoform of NCAM and a novel 210 kDa isoform. Immunoprecipitation and immunoblotting procedures with an antibody specific for a2-8-polysialic acid showed the 180 and 210 kDa isoforms to be polysialylated. The role of NCAM180 sialylation as a mechanism for synapse selection in information storage is discussed. PMID- 1640503 TI - Implication of glucocorticoid receptors in the stimulation of human glioma cell proliferation by dexamethasone. AB - Dexamethasone is frequently used in the therapy of brain tumor patients. We investigated the effect of dexamethasone on the proliferation of three short-term and four established human glioma cell lines in vitro, using a microculture tetrazolium assay to determine growth rates. In one short-term culture and in one established cell line dexamethasone consistently stimulated the proliferation in a concentration-dependent way. The proliferation was maximally enhanced at a concentration of approximately 0.1 microM. In these two cell lines a relatively high level of glucocorticoid receptors was present, whereas low levels of glucocorticoid receptors were found in the other cell lines. In addition, we demonstrated that the stimulatory effects of dexamethasone on the proliferation of the glioma cell lines can be antagonized by the antiglucocorticoid RU38486. The results demonstrate unequivocally that the glucocorticoid receptor plays a role in the growth stimulating effect of dexamethasone. PMID- 1640504 TI - Peanut agglutinin binding glycoproteins in the chick retina: their presence in Muller glia cells. AB - The histological and cellular distribution and some biochemical characteristics of components that bind peanut agglutinin (PNA), a lectin that recognizes preferentially terminal galactose-beta (1-3) N-acetyl galactosamine disaccharide residues of glycoconjugates, were studied in chick retinal tissue and in dissociated retinal cells after their differentiation in culture. In sections of retinal tissue from animals 7 days after hatching (Rp7), in addition to the inner and outer segments of the photoreceptor layer, the plexiform and optic fiber layers were stained with rhodamine-labeled PNA, indicating that, besides photoreceptor cells, other cellular types contribute to the PNA staining. We present evidence indicating that at least part of this staining is provided by Muller glia cells. In cultures of dissociated cells from retinas at embryonic day 7 (R7), photoreceptor-like cells and flat Muller glia-derived cells but not neurons were stained with rhodamine-labeled PNA. Furthermore, Muller glia cells isolated from Rp7 were also brightly stained with PNA. Western blot assays of extracts from R7 showed the presence of PNA binding glycoproteins of 31-33 kDa and a component that migrates at the dye front. In addition to the components detected in R7, extracts from R14 and Rp7 showed the presence of a major PNA binding glycoprotein of 175 kDa and a minor glycoprotein of 220 kDa. Extracts from the photoreceptor layer contain the 175 and 220 kDa glycoproteins, indicating their association with photoreceptor cells. The 31-33 kDa components were detected in extracts from the remnant inner retina, suggesting their association with the Muller glia cells. Supporting this view, these components and not those of 175 and 220 kDa were detected in cell cultures enriched in flat Muller glia-derived cells. Only the 31-33 kDa components and the component that migrates at the dye front were detected in extracts from cell cultures enriched in photoreceptor-like cells, suggesting the need of some environmental element for the expression of the 175 and 220 kDa components in the differentiated photoreceptor cells. PMID- 1640505 TI - Distribution of calcium-activated neutral protease inhibitor in the central nervous system of the rat. AB - The ubiquitous existence of calcium-activated neutral protease (CANP, calpain), an enzyme whose activity is regulated by calcium ions and a specific endogenous CANP inhibitor (calpastatin), is well known. Although there has been much investigation concerning the distribution and role of CANP, investigations of the distribution of the CANP inhibitor using immunohistochemical techniques are rare. We made antiserum against a 40K fragment of cDNA corresponding to two C-terminal repeats of rat liver CANP inhibitor expressed in Escherichia coli. Using this antiserum, we examined the distribution of CANP inhibitor in the rat central nervous system by the ABC technique and compared it with the distribution of CANP. Neurons and glias were stained, with the cytosol stained diffusely and the cell membranes stained clearly and strongly. Axons and myelin were stained faintly, but nuclei and vessels were not stained. The distribution of CANP inhibitor was thus found to be similar to that of CANP. PMID- 1640506 TI - Heptyl-physostigmine enhances basal forebrain control of cortical cerebral blood flow. AB - This study sought to determine the effect of heptylphysostigmine (H-PHY), a reversible cholinesterase (ChE) inhibitor with greater lipophilicity and longer duration of action than physostigmine, on resting and basal forebrain (BF) elicited increases in cortical cerebral blood flow (CBF). Laser-doppler flowmetry (LDF) was used to monitor changes in frontal cortical microvascular perfusion in urethane anesthetized rats. Responses were measured before, early after, and 1 hr following H-PHY, 3 mg/kg, i.m. Electrical stimulation (100 microA) of the BF elicited up to 220% increases in CBF at 50 Hz, an effect that was graded with frequency. At 15 min following H-PHY (3 mg/kg) resting cortical CBF was unchanged, whereas BF-elicited increases were potentiated 47% at 50 Hz. At 1 hour, resting cortical CBF remained unchanged, and the BF-elicited responses were remarkably potentiated by 354% at 10 Hz and 67% at 50 Hz. Acetylcholinesterase (AChE) activity measured in the tissue directly beneath the LDF probe was decreased by 84% at a time when these CBF responses were enhanced. These data suggest that H-PHY substantially enhances the regulation of cortical CBF by the BF, an effect that may be linked to inhibition of cortical AChE activity. This enhancement of cortical CBF may contribute to the efficacy of H-PHY as a treatment for Alzheimer's disease. PMID- 1640507 TI - Transient, cyclic changes in mouse visual cell gene products during the light dark cycle. AB - Temporal and spatial changes in the cellular and subcellular concentrations of photoreceptor cell gene products appear to be important features of phototransduction in rod photoreceptor cells. The time course of the rapid, light dependent movement of S-antigen (S-Ag) (48k; Arrestin) from the inner segments to the outer segments was analyzed using polyclonal and monoclonal antibodies. The concentrations of mRNA change about threefold for rhodopsin and about sixfold for S-Ag in cyclic, independent modes during the normal light-dark cycle. Kinetic analysis indicates that the oscillations of S-Ag mRNA levels are due to changes in the transcriptional activity of the gene itself. An experimental model is presented summarizing the relationships between mRNA levels, protein localization, disc shedding, and phototransduction in the photoreceptors cells. PMID- 1640508 TI - The effect of obstruction on the developing bladder. AB - Congenital bladder obstruction causes significant immediate and long-term consequences yet its pathophysiology remains poorly understood. A model of early fetal bladder obstruction in sheep has been developed to study the response of the developing bladder to high grade obstruction, with particular emphasis on the regulation of growth and development. Congenital bladder obstruction was produced in fetal sheep at 60 days of gestation and studied at 95 days of gestation (14 sheep) or term (12 sheep). A total of 24 age-matched normal sheep served as controls. Bladders were analyzed by total weight, stereological estimation of smooth muscle cell size, number and total mass, deoxyribonucleic acid concentration, muscarinic cholinergic receptor density, myosin isoform analysis and/or passive cystometrics. Congenital bladder obstruction caused a 4.6 times increase in bladder weight at term reflecting a 5.8 times increase in smooth muscle mass. This increase was predominantly that of cellular hypertrophy and less so of hyperplasia, based upon increased cell volume, increased protein-to deoxyribonucleic acid ratio, and no significant increase in total cell number. Muscarinic cholinergic receptor number per smooth muscle cell increased 3.2 times but it did not change relative to myosin content. The ratio of myosin heavy chain isoforms SM1:SM2 is developmentally regulated and was seen to change from 1.6 at 100 days of gestation to 1.13 at term in normals. After 5 weeks of obstruction SM1:SM2 was 1.27 and it was 1.25 at term, indicating an effect on the developmental regulation of smooth muscle. Rapid fill cystometry in vivo measured the rate of stress relaxation to assess accommodative properties. The half-decay time was increased in all 3 obstructed bladders tested to greater than 15 seconds at 50% capacity (normal less than 5 seconds), suggesting reduced compliance. This study shows that an in utero model of bladder obstruction is feasible. Congenital bladder obstruction produces a variety of structural, biochemical and functional changes in the developing bladder indicative of alterations in the regulation of growth and differentiation. PMID- 1640509 TI - Papers presented at the annual meeting of the section of Urology, American Academy of Pediatrics. New Orleans, Louisiana, October 26-31, 1991. PMID- 1640510 TI - Acute hemodynamic and endocrinological effects of partial fetal bladder obstruction. AB - The pathophysiology of fetal urinary obstruction has not been elucidated. Using a unique, reproducible and easily reversible animal preparation, we studied the acute hemodynamic and endocrinological responses to partial fetal bladder obstruction in 16 ovine fetuses at 115 days of gestation (term 147 days). After partial obstruction blood pressure and renal weight increased significantly for at least 72 hours. Renal blood flow trended upwards, particularly from 24 to 72 hours, although this change was not statistically significant. Plasma renin activity was significantly increased during the first 24 hours after obstruction but it returned to baseline thereafter. Plasma cortisol or catecholamine concentrations remained unchanged. The time course and pattern of hemodynamic changes in this fetal sheep preparation of partial urinary obstruction differ significantly from those reported in other preparations. PMID- 1640511 TI - The response of the fetal kidney to obstruction. AB - In a fetal ovine model the renal effects of different anatomic levels of fetal urinary obstruction were studied. Parameters of prenatal renal growth and differentiation were characterized and correlated with the patterns of renal response to in utero obstruction. Complete ureteral or urethral obstruction was produced in the sheep fetus at 55 to 60 days of gestation. Animals were delivered and sacrificed at near term (140 days), and the kidneys were removed and prepared for analysis. Parameters examined included weight, histology, glomerular number and total surface area, as well as urinary sodium, creatinine, osmolarity and N acetyl glucosaminidase. Three patterns of response were identified, producing hydronephrotic, cystic or dysgenetic kidneys. Hydronephrotic kidneys were usually the result of bladder outlet obstruction or ureteral obstruction with spontaneous urinary decompression. These kidneys were large (20.7 gm. versus normal 10.8 gm., p less than 0.0001), with thinning of cortical parenchyma that was structurally intact. Glomerular number and surface area were normal. Cystic kidneys were large (14.2 gm., p less than 0.05) with grossly visible cysts and an effaced medulla. Cortical structure was distorted by cysts but basic elements were intact. Glomerular number and surface area were not reduced. Dysgenetic kidneys were small (3.9 gm., p less than 0.0001) with markedly abnormal cortical structure and little recognizable medulla. Histological elements similar to fetal structures were present, including cuboidal/columnar tubular epithelium and peritubular mesenchymal collars. Glomerular number and surface area were significantly less than normal (p less than 0.001). The kidneys contralateral to unilaterally obstructed kidneys were significantly larger than normal (16.2 gm., p less than 0.0001), with normal histology, glomerular number and surface area, indicating in utero contralateral renal hypertrophy. Urinary sodium was variably affected in the hydronephrotic kidneys and was identical to plasma in the dysgenetic kidneys. These results indicate the technical feasibility of in utero models of urinary obstruction. Renal growth and patterns of differentiation were markedly affected by in utero obstruction. They should be a major focus in the investigation of congenital obstructive uropathy, since normal processes of renal growth and differentiation form the basis for postnatal function. PMID- 1640512 TI - Renal growth factor expression during the early phase of experimental hydronephrosis. AB - Unilateral ureteral obstruction in the rat leads to hydronephrosis of the affected kidney and renal cell deletion through the process of apoptosis. We studied this experimental model to determine whether acute alterations in renal growth factor expression might be involved in the initiation of the apoptotic response. Northern blot analysis of hydronephrotic, contralateral and sham operated kidney polyadenylated messenger ribonucleic acid (mRNA) was performed to quantitate the expression of mRNA encoding the growth factors epidermal growth factor, transforming growth factor-beta and insulin-like growth factor II during the first 48 hours following ureteral obstruction. Although the expression of the insulin-like growth factor II mRNA was unchanged by ureteral obstruction, the expression of epidermal growth factor mRNA rapidly declined in the obstructed kidney during this period. The loss of epidermal growth factor expression was further confirmed by an immunocytochemical staining procedure that demonstrated high concentrations of epidermal growth factor in control renal tubules and a drastic loss of this staining in obstructed renal tubules. In contrast, expression of transforming growth factor-beta mRNA increased in the obstructed kidney. We believe that the altered growth factor environment of the hydronephrotic kidney might be an initiating factor in the onset of renal apoptosis associated with this condition. PMID- 1640513 TI - Late onset severe oligohydramnios associated with genitourinary abnormalities. AB - We evaluated the diagnosis, gestational age at presentation, timing and mode of delivery, and ultimate outcome in those fetuses with third trimester onset of severe oligohydramnios who also had urinary tract abnormalities. A total of 8 fetuses with obstructive uropathy or cystic renal disease was seen during a 2 year period with the onset of severe oligohydramnios noted between 27 and 33 weeks. Immediate and late postnatal pulmonary function was excellent in 5 of the 8 subjects. Three neonates had respiratory distress but only 1 died at birth. Ultimate renal function varied in the 7 survivors. Those with supravesical obstructive uropathy achieved a normal serum creatinine, while the neonates with renal cystic disease and infravesical obstruction did not. PMID- 1640514 TI - Microanatomy and morphometry of the hydronephrotic "obstructed" renal pelvis in asymptomatic infants. AB - There has been limited histological study of the obstructed ureteropelvic junction in patients less than 1 year old. We present our prospective studies on the histomorphometry of the ureteropelvic junction complexes of 35 infants, of whom 23 underwent pyeloplasty for obstruction and 12 were age matched autopsy normals. Qualitatively, the major abnormalities of the pelvic microanatomy in the hydronephrotic obstructed kidneys included a lamina muscularis that was significantly thicker than normal and the presence of collagen fibers between muscle fascicles. Additionally, variable amounts of elastin were present in the adventitia and lamina muscularis. At the ureteropelvic junction the abnormalities were an increase in the number of inner longitudinal muscle bundles, collagen between muscle bundles (p less than 0.016) and elastin in the adventitia. Quantitatively, for the pelvis the lamina muscularis was significantly thicker in 18 obstructed kidneys compared to 7 controls (1,075 +/- 79 mu. versus 420 +/- 63 mu., mean +/- standard error of mean, p less than 0.001). The percentage area density of smooth muscle in the obstructed versus normals was increased (45.1% versus 35.2%, p less than 0.039). The percentage area density of collagen in the obstructed specimens versus normal showed an upward trend (38.6% versus 27.6%), which was not significant. In conclusion, the obstructed ureteropelvic junction complexes of kidneys in asymptomatic infants show significant qualitative and quantitative differences from normal. PMID- 1640515 TI - Nonoperative management of unilateral neonatal hydronephrosis. AB - We followed nonoperatively 45 neonates with unilateral hydronephrosis and suspected ureteropelvic junction obstruction for 30 months, regardless of the degree of hydronephrosis, shape of diuretic renogram washout curve or initial degree of functional impairment. Of the patients 30 had mild hydronephrosis and no renal deterioration, while 15 had severe hydronephrosis, an obstructed diuretic renogram and markedly decreased hydronephrotic kidney function. During followup percentage and absolute renal function rapidly increased in all patients, hydronephrosis improved in 7 and contralateral compensatory hypertrophy did not develop in any. These findings help to define the natural history of untreated hydronephrosis, suggest that many newborn kidneys with severe hydronephrosis are not obstructed despite even profound initial decreases in renal function and demonstrate that traditional tests for diagnosing obstruction are inaccurate in this age group. Therefore, the methods for assessing obstruction and the indications for surgical intervention in these patients require reexamination. PMID- 1640516 TI - Influence of initial therapy on progression of renal failure and body growth in children with posterior urethral valves. AB - Children with posterior urethral valves are at high risk for renal failure and growth retardation. It has been proposed that the type of initial surgical treatment (that is primary ablation versus high diversion) can affect the outcome of children with posterior urethral valves. We evaluated 43 children with posterior urethral valves treated and followed at our hospital from 1975 to 1990 (17 since birth and 26 referred patients). A total of 19 patients was treated by a high urinary diversion, (high urinary diversion group), 19 were treated by primary fulguration and 2 by vesicostomy (fulguration and vesicostomy group), and 3 underwent fulguration and unilateral diversion (mixed treatment group, excluded from study). The clinical outcome and body growth were compared for the high urinary diversion, and fulguration and vesicostomy groups. A normal stature (above the 25th percentile) was reached by 4 patients (21%) from the high urinary diversion group and 11 (52%) in the fulguration and vesicostomy group. This difference was not statistically significant. In contrast, renal function was predictive of body growth: 73% of the children with normal serum creatinine and 20% of the children with renal failure achieved a normal stature (p less than 0.05). One patient from the mixed treatment group died of pulmonary hypoplasia. We conclude that the type of primary surgical treatment (fulguration and vesicostomy or high urinary diversion) did not influence progression of renal failure or body growth in children with posterior urethral valves. Regardless of the surgical or medical treatment, which can greatly influence mortality, renal failure developed in almost 50% of the children with posterior urethral valves. PMID- 1640517 TI - The swing of the pendulum. PMID- 1640518 TI - Biodegradable pericardial implants for bladder augmentation: a 2.5-year study in dogs. AB - Bladder augmentation using biodegradable pericardial tissue was evaluated in canine bladders. Acetic acid and acetic anhydride treated pericardial tissue grafts were stored in 75% ethanol for 18 to 27 months before implant. Ten dogs weighing 20 to 25 kg. were subjected to a 50% partial cystectomy. After careful separation of the mucosa, bladder muscle and adventitial layers a pericardial graft volumetrically equivalent to the portion of the bladder removed was sutured to the bladder remnant in 2 layers. In 1 control dog the bladder was opened, 50% of the bladder was removed and the bladder was closed primarily. In another control dog the excised bladder was replaced with fresh chemically treated patch material that was never subjected to ethanol storage. Excretory urography and cystography were performed on all dogs. Urodynamics with filling pressures and bladder volumes measured before and after the operation at intervals of up to 36 months confirmed that adequate bladder capacity was achieved. There were no operative complications. Postmortem histological evaluations revealed a smooth epithelialized inner surface with no traces of any surface irregularities or suture lines. The bladder apex showed an intact epithelium and the absence of a smooth muscle layer. The biodegradable acetylated tissue provides an intact structural reservoir for urine and serves as a template for epithelial regeneration. This permits volumetric bladder enlargement while the graft is progressively reabsorbed with time. PMID- 1640519 TI - Is lamina propria matrix responsible for normal bladder compliance? AB - Immunohistochemistry using monoclonal and polyclonal antibodies to extracellular matrix proteins is a highly sensitive tool for the characterization of matrix components. For the first time in the normal and noncompliant human bladder we have used antibodies to collagen types I, III and IV, and elastin to provide morphological correlation with mechanical properties noted clinically. In the normal bladder elastin and collagen types I and III showed intense localization in the lamina propria with modest localization in the detrusor layer. In contrast, lamina propria staining in the noncompliant bladder was essentially unchanged, while there was intense localization within the detrusor layer. Significantly, this intense localization consisted of collagen type III and elastin with little increase in type I. Type IV collagen is associated with basement membranes and individual smooth muscle cells, and shows commensurate increase in specimens with muscle hypertrophy and/or hyperplasia. These observations suggest that in the normal bladder the lamina propria may be a major structural capacitance layer with the smooth muscle covering it. The collagen fibers of the lamina propria may gradually unfold during filling, thus, accounting for normal compliance while in the noncompliant bladder the capacitance layer shifts outward to the infiltrated smooth muscle, thus, preventing the normal expansion of the lamina propria. The smooth muscle infiltration consists of a deposition of collagen type III and elastin with little increase of collagen type I, and it results in a loss of compliance. The pattern of localization would suggest that the smooth muscle is responsible for this accumulation. PMID- 1640520 TI - Transurethral intravesical electrotherapy for neurogenic bladder dysfunction in children with myelodysplasia: a prospective, randomized clinical trial. AB - Myelomeningocele is the most common cause of neurogenic bladder dysfunction in children. Urinary incontinence is socially disabling for many of these children and undetected elevations in detrusor pressure can lead to serious upper tract damage. Sensory receptors in the bladder mucosa and submucosa provide afferent information to the central nervous system regulating the micturition reflex. Since 1959 Katona and several other investigators have used intravesical electrotherapy for diagnosis and treatment of the neuropathic bladder. Our objective was to conduct a randomized, sham controlled and blinded clinical study on the efficacy of transurethral intravesical electrotherapy in treating urinary incontinence in the myelodysplastic child. A total of 36 children was enrolled in the study and 31 completed the entire protocol. Of the patients completing the study 13 were randomly selected to serve as an internal sham control having the electrocatheter placed without activating the stimulator. These patients were subsequently treated with a 3-week course of electrotherapy. The remaining 18 patients completing the study were randomly selected to undergo 2, 3-week courses of intravesical bladder stimulation. Urodynamic studies were performed before and after each treatment series. Detailed daily questionnaires were submitted to each participant covering subjective improvement in urinary continence and any development of bladder sensory awareness. Analysis of the urodynamic data and questionnaires failed to reveal any statistically significant increase in bladder capacity, development of detrusor contractions, improvement in detrusor compliance or the acquisition of bladder sensation allowing timely intermittent catheterization preventing urinary incontinence. PMID- 1640521 TI - Expression of a Wilms tumor gene in porcine kidney during compensatory renal growth. AB - Expression of the putative Wilms tumor gene (WT-1) was studied to investigate its role in renal growth. Compensatory renal growth was induced in 35-day-old Yorkshire-swine by unilateral nephrectomy. The contralateral kidney was removed 0.5 to 72 hours following the initial operation and analyzed for WT-1 gene expression by Northern analysis. Compensatory renal growth was detectable by wet weight measurements at 12 hours following contralateral nephrectomy. WT-1 gene expression was detectable in the contralateral kidney as early as 0.5 hours following unilateral nephrectomy. Expression of this gene was not detected in normal kidney from swine of this age group or from sham operated swine. In addition, we demonstrated the expression of this gene in newborn rat, pig and human kidneys, as well as human fetal kidney, indicating its role in nephrogenesis. These data suggest that expression of the WT-1 gene is involved in the regulatory mechanisms that control different types of renal growth. PMID- 1640522 TI - The effect of bacteriuria on bladder and renal pelvic pressures in the rat. AB - We investigated the effect of urinary tract infection on bladder and renal pelvic urodynamics in a rat model to examine the role of pressure during infection. Either an antibiotic solution (control group) or Escherichia coli with type 1 pili (infected group) was instilled into the bladder. After 2 to 6 days simultaneous continuous bladder and renal pelvic pressures were measured during urinary flows from less than 2 to greater than 20 ml./kg. per hour while the bladder filled and emptied. Bladder pressures from 50 to 100% of maximum capacity and maximum voiding pressures were significantly higher in the infected group than the control group (36.7 +/- 6.79 cm. water versus 25.5 +/- 5.21 cm. water, respectively, p less than 0.0001). Renal pelvic pressures were significantly higher in the infected group during bladder filling at all urinary flows examined and actually exceeded bladder pressure for the highest flows. We conclude that elevated renal pelvic pressures may contribute to renal changes observed during urinary tract infection. PMID- 1640523 TI - The effects of ileocystoplasty on the development of renal failure in a rat model 5/6 nephrectomy. AB - We examined the effects of ileocystoplasty on renal function and bone mineral content in 160 juvenile male Wistar-Furth rats with and without renal insufficiency induced by 5/6 nephrectomy. At intervals up to 20 weeks blood, bone and kidney samples were obtained with the animals under anesthesia and then they were sacrificed. Serum parameters of renal function and calcium metabolism were measured. Samples of bone were analyzed for calcium, magnesium and phosphorus content. At 20 weeks after 5/6 nephrectomy renal function was decreased by approximately half. The decrease in renal function and the changes in renal histology were identical in animals with and without ileocystoplasty. Bone mineral content in the animals with renal insufficiency with or without ileocystoplasty was not different from sham operated animals or from animals with an ileocystoplasty and normal renal function. These studies demonstrate that ileocystoplasty per se does not hasten the progression to renal failure or produce bone demineralization in rats having moderate renal insufficiency. PMID- 1640524 TI - The influence of urinary diversion on experimental gastrocystoplasty. AB - Gastrocystoplasty is used to augment the bladder of patients with decreased renal function to prevent development or worsening of metabolic acidosis. We recently observed a perforated peptic ulcer in the gastric portion of a defunctionalized gastrocystoplasty. We postulated that the lack of buffering action of urine precipitated peptic ulcer disease in the gastrocystoplasty. To explore this possibility further, we conducted an experiment. In 12 adult female mongrel dogs (weight 15 to 26 kg.) the bladder was divided into right and left segments. One kidney was removed and both hemibladders were capped with a vascularized segment of gastric body. Thus, 1 side (wet) remained exposed to urine, while the other side (dry) was drained to the abdominal wall with a cystostomy tube. The animals were divided into 2 groups: 9 in group 1 received no drugs to modify gastric secretion and 3 in group 2 received a hydrogen (H2) blocker. Three animals in group 1 had perforation of the vesical part of the dry gastrocystoplasty 2 to 3 weeks postoperatively and were sacrificed. The others were sacrificed 3 to 6 weeks postoperatively. Serum gastrin levels remained normal in all animals. Gross and histological examinations of the augmented bladders in group 1 revealed ulcerations of the bladder segment of the wet and dry gastrocystoplasties but the lesions were more numerous and prominent on the dry side in all animals, particularly those in which the perforations occurred. A peptic ulcer was noted in the gastric portion of the dry gastrocystoplasty in 1 animal. The bladder epithelium of the dry gastrocystoplasty showed glandular metaplasia in several animals in this group. In group 2 the wet gastrocystoplasty showed normal histology except in 1 dog that had mild inflammation and focal superficial ulceration in the vesical portion. On the other hand, the dry gastrocystoplasty showed severe inflammation and ulcerations in 2 animals, and mild inflammation of the vesical portion in 1. There were no perforations in this group. This experiment demonstrates that gastrocystoplasty produces cystitis but that these changes are more prominent in the absence of urine, as indicated by the severity of the lesions, perforations and metaplasia. Peptic ulcer disease occurred in the gastric portion of the dry gastrocystoplasty in 1 animal. The use of H2 blockers decreases the incidence of ulceration in wet gastrocystoplasty but it seems to have less influence on the ulceration of dry gastrocystoplasty. Clinicians must be alerted to the risk of perforation of dry gastrocystoplasty. PMID- 1640525 TI - Lithogenic properties of enterocystoplasty. AB - Calculi formed in 26 of 87 patients (30%) following augmentation enterocystoplasty, of which 23 formed within the reservoir, at a mean interval of 25 months postoperatively. The calculi were composed principally of triple phosphates suggesting an important etiological role of bacteriuria and the urease reaction. Open cystolithotomy was the most successful means of removing the calculi. PMID- 1640526 TI - The urofacial (Ochoa) syndrome revisited. PMID- 1640527 TI - The value of urodynamic studies in infants less than 1 year old with congenital spinal dysraphism. AB - The role and timing of urodynamic studies in infants with congenital spinal dysraphism are controversial. We reviewed 64 consecutive infants with a mean followup of 28 months who underwent video urodynamic study when they were less than 1 year old (50 of the 64 patients were less than 3 months old). A previously reported video urodynamic "hostility score" from 0 (best) to 10 (worst) was given to each study and compared with the outcome of the upper urinary tract and subsequent urodynamic studies. A larger fraction of these children with high hostility scores (5 or greater) had upper tract deterioration (39%) compared to those with low hostility scores (9%). Moreover, 6 of 14 patients in the low hostility group who underwent repeat video urodynamic studies after age 1 year had high hostility lower urinary tracts. We conclude that urodynamic studies during and after the first year of life are useful in the appropriate urological evaluation and management of infants with spinal dysraphism. PMID- 1640528 TI - Pitfalls in determination of leak point pressure. AB - To evaluate the influence of the technical aspects of leak point pressure measurement we performed water cystometry and determined the leak point pressure in 23 patients 5 weeks to 21 years old with neurogenic bladders. We initially assessed the influence of catheter size on the leak point pressure and determined that the measured pressure varied in direct proportion to the catheter diameter. We further evaluated the effect of the method of infusion (gravity drip versus pump) and the infusion rate on pressures measured by a transducer in an in vitro setting. Using the gravity drip infusion technique pressure measurement was adversely affected by smaller catheter size and rapid infusion rate. With the pump infusion system neither catheter size nor infusion rate adversely affected pressure measurement. We conclude that the clinical measurement of the leak point pressure during water cystometry is influenced by the catheter size, and it is dependent upon the technique and rate of infusion. We believe that standardization of the technical aspects of leak point pressure determination would provide for reproducible results and facilitate comparisons of reports among different investigators. PMID- 1640529 TI - Bladder functional changes resulting from lipomyelomeningocele repair. AB - From 1986 to 1991, 12 boys and 23 girls underwent surgery for lipomyelomeningocele removal. Of these patients 29 were 15 months old or younger (average age 3 months), while 6 were 4.5 to 19 years old (average age 10 years). Preoperative and postoperative urodynamic studies, including external urethral sphincter electromyography, were done on everyone. All 29 infants had a cutaneous lesion overlying the lower back and 14 had an abnormal neurological examination. Preoperative urodynamic studies were abnormal in 11 patients, consisting of an upper motor neuron lesion in 6, and a mixed upper and lower motor neuron lesion in 5. Postoperatively, 10 of 14 children with an abnormal neurological examination improved, while 9 of 11 with abnormal lower urinary tract function normalized. In 1 of 18 children (6%) with normal preoperative urodynamic studies detrusor-sphincter dyssynergia developed postoperatively. In all 6 older children urinary incontinence developed, and this led to the diagnosis. Everyone had an abnormal neurological examination and abnormal preoperative urodynamic studies. One child had a lower motor neuron lesion, and 5 had a mixed upper and lower motor neuron lesion. Postoperatively, the neurological examination improved in only 1 patient (16%), and the urological symptoms and urodynamic findings improved in another child. Lipomyelomeningocele has a progressive effect on lower spinal cord function because infants tend to present with fewer urinary manifestations and physical findings than older children. Individuals who escape early detection tend to have a more subtle cutaneous abnormality. As a result, older children are more likely to present with urological and neurological complaints. Surgical correction in infancy provides a degree of reversibility not seen in older children. It is imperative that early identification, evaluation and treatment be undertaken to prevent this progression and permanency of neurological changes and urinary dysfunction. PMID- 1640530 TI - The pharmacokinetics of intravesical and oral oxybutynin chloride. AB - In 8 children with cystometric evidence of bladder instability and marked systemic side effects to oral oxybutynin we investigated the efficacy of intravesical instillation and compared the pharmacokinetics of both routes of delivery. In addition, 4 healthy dogs underwent intravesical instillation for pharmacokinetic studies. Intravesical oxybutynin was well tolerated, efficacious and rapidly absorbed, resulting in plasma concentrations markedly higher than after oral administration. In only 2 patients did this method of instillation result in side effects, and both had previously undergone bladder augmentation. This lack of significant systemic side effects despite high plasma concentrations suggests that a metabolite may be generated after oral administration that is responsible for the side effects. These studies demonstrate that the mode of administration affects the mechanism of action, side effects, pharmacokinetics and metabolism of oxybutynin, and that intravesical instillation is clinically effective and results in minimal side effects. PMID- 1640531 TI - Pronounced detrusor hypercontractility in infants with gross bilateral reflux. AB - In this study the prevalence of bladder dysfunction in 18 children with gross bilateral reflux was investigated via cystometric recordings. In all except 1 infant maximal voiding detrusor pressure was 100 cm. or greater water (range 86 to 244). Pronounced instability during filling (overt instability) with pressure waves above baseline (mean 65 cm. water, range 42 to 194) was found in 9 infants. Another 5 children had evidence to suggest an uninhibited bladder, not manifested as unstable contractions during filling but as covert instability, meaning that the first unstable contraction was transformed into a premature and forceful voiding contraction. The high detrusor pressures found in 18 children with gross bilateral reflux during the voiding phase but also during the filling phase in half of the children suggest that a hypercontractile detrusor may be a contributory factor for the development of reflux even in this age group. PMID- 1640532 TI - The efficiency of bladder emptying in the prune belly syndrome. AB - From 1956 to 1991, 49 cases of the prune belly syndrome were seen at our institution. Voiding information and/or 1 or more urodynamic studies were available in 30 male and 4 female patients. Analysis of multiple urodynamic studies during long-term followup periods ranging from 6 months to 19 years, with particular regard to any reconstructive procedures performed, revealed that voiding in the prune belly syndrome is variable, with 44% of the patients achieving spontaneous voiding and 56% requiring clean intermittent catheterization. The ability to void or need for clean intermittent catheterization was by no means permanent, indicating the need for meticulous followup. The 3 distinct voiding patterns observed included an approximately normal pattern, prolonged voiding with a low peak and an intermittent pattern. These 3 voiding patterns did not correlate with residual volumes. Comparison of urodynamic voiding parameters between reconstructed voiding patients and nonreconstructed voiding patients did not show significant differences. PMID- 1640533 TI - Postnatal ultrasound screening of urinary malformations. AB - We performed routine neonatal ultrasound screening on 3,454 neonates in the first week of life to establish the real incidence of congenital uropathy. Pronounced anomalies were found in 36 cases (1.04%) and mild renal pelvis dilatation in 159 (4.60%). In the population study prenatal ultrasonography showed evidence of severe anomalies in only 7 fetuses (0.2%). Surgical correction was required in 14 cases. Our results indicate that neonatal ultrasound screening has sufficient sensitivity and specificity for the early detection of the vast majority of urinary tract malformations. In 2 cases mild vesicoureteral reflux was not detected until a urinary tract infection was noted. Thus, neonatal sonography appears to be of limited value in detecting mild reflux. PMID- 1640534 TI - The sensitivity of renal scintigraphy and sonography in detecting nonobstructive acute pyelonephritis. AB - Recently it has been demonstrated that any child with proved acute pyelonephritis may be at risk for parenchymal scarring, whether or not reflux is present. Since cortical renal scintigraphy has been shown to detect accurately renal inflammation, we compared cortical scintigraphy with renal sonography in 46 children with documented acute pyelonephritis to determine which modality is best to detect patients at risk for renal injury. Cortical scintigraphy was abnormal in 36 children (78%) and renal ultrasonography was abnormal in 5 (11%). Reflux was demonstrated in only 20 cases (43%). We conclude that cortical scintigraphy is the preferred imaging technique for diagnosing renal inflammation, and it should be used routinely in every child with suspected acute pyelonephritis. A new imaging protocol is proposed. PMID- 1640535 TI - Grading nephroureteral dilatation detected in the first year of life: correlation with obstruction. AB - To understand better the significance of pediatric idiopathic nephroureteral dilatation the renal ultrasound images of patients less than 1 year old with hydronephrosis or hydroureteronephrosis were graded and compared to the radiological diagnosis of obstruction as determined by diuresis renography and/or urography. The study included 73 boys and 30 girls with hydronephrosis (76 patients) or hydroureteronephrosis (27). For hydronephrosis obstruction was diagnosed in 56 children (74%) and involved 61 of 97 kidneys (63%). For obstructed kidneys the mean grade of hydronephrosis (3.4 +/- 0.7 standard deviation) was statistically different from that of nonobstructed kidneys (1.6 +/ 0.8 standard deviation) (p less than 0.05). When the value to predict obstruction was set at grade 3 hydronephrosis or greater there was an 88% sensitivity and 95% specificity. For hydroureteronephrosis obstruction was diagnosed in 15 of 27 children (56%) and involved 17 of 34 kidneys (50%). The degree of dilatation was weighted as a score to assess the grades of hydronephrosis and ureteral dilatation, namely hydroureteronephrosis score equals grade of hydronephrosis plus grade of ureteral dilatation. In obstructed megaureters the mean hydroureteronephrosis score (5.8 +/- 1.0) was statistically different from that for nonobstructed megaureters (mean hydroureteronephrosis score 2.7 +/- 1.9) (p less than 0.001). When the value to predict obstruction was set at hydroureteronephrosis score of 5 or greater there was a 94% sensitivity and 80% specificity. Although ultrasound examination alone cannot be used to diagnose urinary obstruction, the radiological diagnosis of obstruction is linked with the grade of hydronephrosis or score of hydroureteronephrosis. PMID- 1640536 TI - The effect of polyethylene glycol-superoxide dismutase administration on histological damage following spermatic cord torsion. AB - Oxygen free radicals generated during the ischemic/reperfusion period have been suggested as a possible cause for tissue damage in different organs. In this study we address the question of whether administration of polyethylene glycol superoxide dismutase, an oxygen free radical scavenger, can alleviate histological damage associated with testicular torsion. The study included 67 Sprague-Dawley rats. In 60 rats the left testicle was rotated 720 degrees clockwise through a scrotal incision. Torsion duration was 3 hours. Five minutes before and 5 minutes after detorsion the testicle color was evaluated and scored. The remaining 7 rats underwent a sham operation. After randomization 8,000 units per kg. polyethylene glycol-superoxide dismutase were injected intraperitoneally in the treated group 1 hour before detorsion. After 14 days histological evaluation was performed on both testicles of 58 rats (2 rats died before the evaluation). No statistically significant difference was demonstrated between the treatment (28 rats) and the control groups (30 rats). Testicular color after detorsion correlated with the histological damage. PMID- 1640537 TI - Injectable bioglass as a potential substitute for injectable polytetrafluoroethylene. AB - Injectable polytetrafluoroethylene (Teflon) and collagen have inherent problems that may prevent their long-term success. In search of a different injectable biomaterial we confirmed in rabbits the safety of injected Bioglass particles suspended in sodium hyaluronate. A second study was performed testing the ability of the Bioglass suspension to increase urethral resistance in pigs. Bioglass particles in suspension have the potential to substitute for polytetrafluoroethylene or collagen in the treatment of urinary incontinence or vesicoureteral reflux. PMID- 1640538 TI - Selective sacral rhizotomy in children with high pressure neurogenic bladders: preliminary results. AB - Recent successful introduction of selective rhizotomy in the management of lower extremity spasticity in patients with myelodysplasia has prompted us to use it as a means of managing high pressure neurogenic bladders occasionally encountered in myelodysplastic patients. During the last 1 1/2 years 8 children have undergone selective sacral rhizotomy in an attempt to avert urinary diversion or bladder augmentation. Patient age ranged from 6.5 to 18.5 years. The level of the respective lesions was evenly distributed throughout the spine. At spinal surgery each patient had an electrode placed in the detrusor of the bladder via a suprapubic approach, electromyography electrodes were placed in the perineum and slow fill water cystometry was performed throughout the procedure. Standard electrophysiological stimulation of the nerve roots was performed to identify the rootlets that would only affect the detrusor and spare the external sphincter. Postoperative followup has been obtained on all patients. Of the patients 4 have exhibited significant improvement and they have not required augmentation, 2 have not shown any further deterioration in bladder function, 1 has demonstrated deterioration and 1 still lacks urodynamic followup. Postoperative cystometric studies have revealed a bladder capacity increase of 69% for the group. Uninhibited bladder contractions were abated in all but 1 patient. No patient has been rendered incontinent of urine from the procedure and no patient has had a problem with stool continence as a result of the rhizotomy. It appears that selective rhizotomy of the sacral roots has been able to increase bladder capacity as well as compliance in patients who normally would have been relegated to either bladder augmentation or urinary diversion. While these are encouraging results, some further followup is required to ascertain if the early improvements will be long-lasting. PMID- 1640539 TI - Transurethral electrical bladder stimulation: initial results. AB - Transurethral electrical bladder stimulation to rehabilitate the neurogenic bladder initially proposed by Katona has been promoted in the United States by Kaplan and Richards since the mid 1980s. Encouraged by their results, 2 1/2 years ago we instituted a program patterned on their experience. Since January 1989 we performed transurethral electrical bladder stimulation in 21 patients ranging in age from 4 months to 26 years. The cause of the neurogenic bladder was myelomeningocele in 16 patients, lipomeningocele in 4 and an incomplete spinal cord injury in 1. The stimulation was performed using equipment supplied by Kaplan and Richards, and the stimulation protocol followed their recommendations. The treatments were delivered in daily sessions of 90 minutes with about 20 sessions in a series. Of the patients 11 have undergone 1,6 have finished 2 and 4 have completed 3 series of stimulation. The ultimate objective of the program is to achieve volitional voiding. To reach that goal the stimulation must engender a bladder contraction that must then be perceived and ultimately controlled. Of our patients 20 (95%) achieved bladder contractions during stimulation, including 12 (60%) who had either a definite (7) or probable (5) sense of these contractions. To date, only 1 patient has started the biofeedback program to attempt to modify detrusor activity and he is presently wet on clean intermittent catheterization. Parents of 5 other children report minor positive changes in the child's perception of the bladder activity. Three patients noticed an improvement in the bowel program, although the effect only lasted during the month of stimulation in 1. Cystometrograms were performed before each series of treatments. Of the 10 patients with serial studies 2 had significant increases in bladder capacity and 3 demonstrated a clinically significant decrease in the end filling pressures. We have seen limited encouraging results from transurethral electrical bladder stimulation. This is a time-consuming, labor intensive program, and the parents and patients need to be informed of the actual potential for dramatic improvements. PMID- 1640540 TI - Neuromodulation in the management of voiding dysfunction in children. PMID- 1640541 TI - Free bladder mucosal graft biology: unique engraftment characteristics in rabbits. AB - To study the biology of bladder mucosal grafts we developed an animal model using New Zealand white male rabbits. A 25 x 9 mm. segment of bladder mucosa was harvested and tubularized over an 8F catheter using 7-zero polyglactin sutures. An equivalent portion of rabbit urethra was then excised and the graft was anastomosed to this defect in an end-to-end fashion. A urethral catheter was left in place to provide bladder drainage and to stent the anastomosis. Animals were sacrificed on postoperative days 1 to 90. India ink was injected into the aorta at sacrifice to visualize the microvasculature. All 59 specimens were stained with hematoxylin and eosin, and studied using light microscopy. Our results demonstrated vascular ingrowth at 72 hours. Between postoperative days 8 and 10 healthy viable epithelium first bridged the entire urethral defect. By postoperative day 12 the epithelial lining was complete. A poor outcome was observed in all animals whose stents were removed early. We conclude that the biology of bladder mucosal grafts is unique in that the graft initially undergoes partial degeneration followed by regeneration. Of concern are the results of those animals whose stents were removed early. In all such cases a poor outcome was observed. PMID- 1640542 TI - Hypospadias repair using laser welding of ventral skin flap in rabbits: comparison with sutured repair. AB - We tested the feasibility of laser welding in hypospadias repair. A total of 30 New Zealand white rabbits (2 groups of 15) underwent creation of distal hypospadias. In the control group ventrally placed skin flaps were created and sutured to the urethra. In the experimental group the ventrally placed skin flaps were welded to the urethra using a continuous wave diode laser (808 plus or minus 1 nm., 6.25 watts per cm.2). The welded anastomoses were strengthened by applying a solder of fibrinogen combined with a laser energy-absorbing dye. No stents were left indwelling. Operative time using laser welding was considerably less than that with sutured repair. No fistulas were seen in the welded urethras, and no significant foreign body reaction was identified in the laser welded repairs. Hypospadias repair in the rabbit using the laser welding technique seems to be a feasible alternative to suture repair. Topical energy-absorbing dyes that enhance thermosetting solders further increase weld strength while reducing collateral thermal damage to target tissues. PMID- 1640543 TI - True hermaphrodites: an experimental model in the mouse. AB - When the Y chromosome from the Mus musculus domesticus mouse strain is placed onto the C57BL/6J mouse background ovarian and testicular components develop in half of the XY progeny (B6.YDOM), providing an excellent model of true hermaphroditism. We examined the correlation between gonadal sex and development of the internal genital tract in the B6.YDOM mouse at puberty. Of 55 mice examined 20 had bilateral testes, 33 were true hermaphrodites and 2 had mixed gonadal dysgenesis. In all mice with bilateral testes male accessory sexual organs developed bilaterally. In the true hermaphrodites testes were found on either side but preferentially on the left side. When a male feature was present on the ipsilateral side of the ovary, the seminal vesicle was more frequently found than prostate or vas. Testicular mass was significantly different between the true hermaphrodites with and those without bilateral seminal vesicles. Similar difference was found in those with and without bilateral prostates. The serum testosterone level was not significantly different between these groups. We conclude that the testicular mass is a better discriminant than serum testosterone for the presence or absence of seminal vesicles and prostates at puberty. PMID- 1640544 TI - Vaginal replacement in children. AB - Between 1980 and 1990, 17 patients underwent total vaginal replacement at our hospital. The majority of these patients presented with mullerian failure or gender reassignment for intersex. Colon vaginal replacement was done in 15 patients and small bowel was used in 2. Complications included prolapse in 2 patients and stenosis in 2. Of the 17 patients 4 are married, 10 are sexually active, only 1 reports dyspareunia and 1 requires home self-dilation. PMID- 1640546 TI - Salvage pyeloplasty in nonvisualizing hydronephrotic kidney secondary to ureteropelvic junction obstruction. AB - The potential recoverability of an obstructed kidney detected by maternal antenatal ultrasound cannot be predicted by the currently available methods of investigation. Early repair in the presence of little parenchymal tissue may result in marked improvement in renal function. During the last 2 years 8 male and 2 female neonates with antenatal presentation of hydronephrosis were referred for postnatal evaluation. All patients had palpable renal masses clinically, which were unilateral (left side) in 9 and bilateral in 1. Blood urea nitrogen and creatinine were normal in all patients. Postnatal imaging included abdominal ultrasonography, voiding cystourethrography, excretory urography and quantitative functional evaluation with diuretic diethylenetriaminepentaacetic acid renal scan. Nonvisualization of a left hydronephrotic kidney was detected in all cases. Antegrade pyelography at surgical exploration (at age less than 2 months) was done to outline the anatomy. Stretched thinned out renal parenchymal tissue over a hugely distended renal pelvis was present and dismembered reduction pyeloureteroplasty was performed. A nephrostomy tube and ureteral stent were used. Followup ranged between 6 and 24 months. Remarkable recovery of renal function, more than 100% on renal scintigraphy, was noted postoperatively in all patients. PMID- 1640545 TI - Vaginal reconstruction after initial construction of the external genitalia in girls with salt-wasting adrenal hyperplasia. AB - A total of 28 patients with salt-wasting adrenal hyperplasia who underwent revision of the external genitalia at an early age (mean age 21.4 months) has been followed for 12 to 20 years (mean 16.3 years). The age at initial surgery ranged from 3 weeks to 5 years. Twenty-five patients had a low and 3 had a high takeoff of the vagina from the urogenital sinus. Of these children 22 (78.5%) required further vaginal reconstructive procedures to achieve a normal vaginal outlet. Of the 22 patients requiring further repair 18 have undergone vaginal reconstructive procedures with an initial success rate of 72.2%. These long-term data suggest that if vaginal reconstructive surgery is performed in infancy details, such as placement of the perineal flap well into the vagina and careful followup of the vaginal outlet, are mandatory for success. If there is evidence of outlet narrowing, periodic dilation will be needed to prevent vaginal stenosis and further vaginal surgery. PMID- 1640547 TI - Nonoperative management of major blunt renal trauma in children: in-hospital morbidity and long-term followup. AB - The management of 26 children with major renal injury secondary to blunt trauma was reviewed. Emergency computerized tomography (CT) was performed in all instances. Injury ranged from parenchymal laceration to vascular avulsion. Early surgical exploration was done in 5 children due to hemodynamic instability, renal pedicle injury or suspected malignancy. The remaining 21 children were observed. Of these children 5 had associated intra-abdominal organ injuries. The average length of hospitalization was 13.4 days and the average intensive care unit stay was 6.9 days. A third of the children were transfused with an average 10.8 cc/kg. of packed red cells. Ten patients (47.6%) had febrile episodes that lasted an average of 3 days. No foci of infection other than bladder urine were identified and there were no infected perirenal collections. In 2 children ureteral stents were placed cystoscopically. Exploration was performed in 1 child for delayed hemorrhage 2 months after hospital discharge. Followup CT was available in 15 patients and all kidneys functioned, including 3 with residual focal scarring, 2 with parenchymal calcifications and 1 with a cyst. Eleven patients were evaluated clinically at least 1 year after injury and all were asymptomatic, while 1 child had mild diastolic hypertension. In conclusion, nonoperative management results in an excellent long-term outcome in the majority of cases. In-hospital morbidity is minimal and early surgical exploration should be reserved for those with hemodynamic instability or renal pedicle injury. Immediate CT is an invaluable aid in categorizing and managing these patients. PMID- 1640548 TI - Results of varicocele surgery in adolescents: a comparison of techniques. AB - We report our experience using 3 different operative techniques for varicocele ligation in adolescents. Between August 1985 and April 1991 we performed 102 varicocelectomies on 91 adolescents. Varicocele persistence rate was 16% with a modified Ivanissevich inguinal approach and 11% using a selective high retroperitoneal technique with preservation of the internal spermatic artery. Intraoperative post-ligation spermatic venography did not significantly improve the results with the artery sparing techniques. Palomo mass high retroperitoneal ligation of the internal spermatic vessels produced significantly better results compared to the artery sparing techniques. Testicular atrophy did not occur in any patient regardless of the surgical technique used. These data suggest that the Palomo technique results in a significant decrease in the operative failure rate compared to the artery sparing procedures and it should be the preferred technique for varicocele ligation in the adolescent. PMID- 1640549 TI - Significance of accessory ductal structures in hernia sacs. AB - The finding of ductal structures resembling a vas deferens during pathological examination of a hernia sac specimen has significant medical and legal implications. A method of distinguishing these accessory structures from an inadvertently transected vas has been lacking and is needed. Between July 1989 and January 1990 we examined 147 hernia sacs from 105 consecutive prepubertal and adolescent boys to determine the incidence and salient histological features distinguishing these ductal structures from a true vas deferens. Luminal diameters of the ductal structures were compared with published normal age related established vas deferens diameters and with those measured during hernia repair in 10 of our youngest patients. Among the 147 specimens 6 hernia sacs (4.1%) contained ductal structures. We found that the mean ductal diameter (0.263 mm.) was significantly smaller than that of a normal vas deferens (0.69 to 1.5 mm.). Furthermore, the surrounding mantle of tissue of these ductal structures lacked muscle tissue when studied with Masson trichrome stain. We conclude that duct diameter and trichrome staining are simple ways of differentiating these structures from a true vas deferens. PMID- 1640550 TI - Perforation of the augmented bladder. AB - In 12 of 264 children treated with enterocystoplasty 15 spontaneous perforations occurred. Of the 12 children 9 had myelodysplasia. All segments of the gastrointestinal tract were used for the augmentation and most were detubularized. Surgery to increase bladder outlet resistance was done in 8 cases. At the time of each perforation 9 children had sterile cultures, however, 3 died of overwhelming sepsis. Presenting signs included abdominal pain in 8 cases, septic shock in 4 cases and shoulder pain in 4 older myelodysplastic children with diaphragmatic irritation from escaping urine. Cystography demonstrated a leak in 10 of 11 cases. Urodynamic studies revealed good compliance with low maximum filling pressure in 8 of 10 children. Hyperreflexia was noted in only 5 cases and outlet resistance greater than 85 cm. water was demonstrated in 5. Histological analysis showed changes in the bowel wall consistent with ischemia but suture granulomas were present in areas adjacent to the perforation site or thinned areas in biopsy or autopsy specimens. In addition to the theory that overdistention may cause enterocystoplasty perforation, current detubularization techniques may produce areas of relative ischemia, which become accentuated when the augmented bladder is distended beyond a reasonable volume. PMID- 1640551 TI - Extravesical nondismembered ureteroplasty with detrusorrhaphy: a renewed technique to correct vesicoureteral reflux in children. AB - We performed an extravesical nondismembered reimplant to correct surgically primary vesicoureteral reflux in 45 patients (65 renal units) between April 1989 and September 1990. Of the units 6 had grade I reflux, 16 grade II, 23 grade III, 14 grade IV and 6 grade V. Only patients with primary reflux were included in this study. The success rate was 100% for grades I to III, 92.9% for grade IV and 66.7% for grade V. Overall, the reflux was cured in 62 of the 65 operated renal units (95.4%) or 95.6% of the patients (43 of 45). Postoperative morbidity and complications were minimal. No cases of postoperative obstruction were detected on excretory urography 6 weeks postoperatively. Seven children (16%) suffered from transient inadequate bladder emptying as assessed by post-void ultrasound residual evaluations. This problem resolved spontaneously after a maximum of 4 weeks of clean intermittent catheterization. Compared to conventional transvesical technique, the discomfort related to bladder spasms during the postoperative period was subjectively decreased and patients had no prolonged hematuria. PMID- 1640552 TI - Urethral healing in rabbits. AB - We studied urethral healing in New Zealand white rabbits by histological examination after insult (urethral catheter) or injury (urethrotomy) specifically for acute and chronic inflammation, fibrosis, fistulas, squamous metaplasia, foreign body giant cells and urethral dilatation. Urethral catheterization resulted in increased inflammation and fibrosis compared to noncatheterized animals. Skin closure techniques and materials resulted in an inflammatory response that may extend to and involve the urethra. Minor differences in suture size were not an important variable but the persistence of suture material may have a role in the degree of inflammation and the formation of foreign body giant cells. Transepithelial closure techniques drag epithelial cells into subcutaneous tissues and may predispose to fistula formation. PMID- 1640553 TI - Variations in practice among urologists and nephrologists treating children with vesicoureteral reflux. AB - To analyze the current management recommendations among physicians treating children with vesicoureteral reflux, the American Urological Association Reflux Practice Guidelines Panel surveyed 100 pediatric urologists, 100 general urologists and 100 pediatric nephrologists by questionnaire, and received a 60% response. In the evaluation of a 4-year-old girl with bilateral grade 2 reflux general urologists were more likely than the other 2 groups to recommend cystoscopy and urethral dilation. At followup nuclear cystography was recommended by 76% of pediatric urologists, 48% of general urologists and 71% of pediatric nephrologists, while the latter 2 groups were less likely to recommend any subsequent upper tract evaluation. Pediatric urologists were significantly more likely to recommend antireflux surgery if the child had 1 breakthrough febrile urinary tract infection, poor compliance with medical management or persistent reflux at age 11 years. In a 6-year-old girl with unilateral grade 4 reflux and detrusor instability 44% of pediatric urologists recommended antimicrobial prophylaxis and anticholinergic therapy compared to 12% of general urologists and 6% of pediatric nephrologists. Antireflux surgery was recommended by 29% of pediatric urologists, 60% of general urologists and 59% of pediatric nephrologists. In older girls with persistent grade 2 or 3 reflux pediatric urologists were much more likely to recommend antireflux surgery. In contrast, they were less likely to recommend surgery in young girls and boys with newly diagnosed grade 4 reflux. These data demonstrate significant differences in therapeutic recommendations among pediatric urologists, general urologists and pediatric nephrologists, and suggest the need for outcomes research to determine the optimal management of children with vesicoureteral reflux. PMID- 1640554 TI - Subureteral collagen injection for the endoscopic treatment of vesicoureteral reflux in children. Followup study of 97 treated ureters and histological analysis of collagen implants. AB - Endoscopic subureteral injection has become an established alternative means for treating vesicoureteral reflux in select children. However, which injection material to use remains a controversy. Polytetrafluoroethylene (Teflon) has been injected in more than a thousand patients with few complications, although experimental and clinical studies have demonstrated migration of the injected particles into distant organs, such as the lungs and the brain, as well as local and metastatic granuloma formation. Therefore, we introduced, following experimental studies in the mini-pig model, glutaraldehyde cross-linked, highly purified bovine collagen for injection. Between June 1988 and October 1991, 97 refluxing ureters in 66 children were treated by endoscopic subureteral collagen injection. In 58.8% of the ureters reflux was cured after 1 and in 77.3% after 2 injections. Considering improvement to grades I and II reflux without further treatment as success, the success rate increased to 68.0% after 1 and to 89.7% after 2 injections. Mean followup was 18.5 months (range 3 to 39 months). After 2 failed injections the patients either returned to antibiotic long-term prophylaxis or the reflux was operatively corrected. The operative procedure was never compromised by the preceding injection. A direct correlation between deficient length of the submucosal tunnel of the intravesical ureter and the iatrogenic malposition of the collagen deposits, and the failures could be demonstrated. Granuloma formation at the site of injection was not found. The results of the histological investigation of the collagen deposits removed at open ureteral reimplantation for failures are reported. It could be demonstrated that endogenous fibroblasts invade the bovine collagen implant and that these cells show active production of new human collagen, types I and III, replacing the implant. PMID- 1640555 TI - Endoscopic treatment of vesicoureteral reflux with a self-detachable balloon system. AB - There is controversy about the use of polytetrafluoroethylene (Teflon) paste in children for the endoscopic treatment of vesicoureteral reflux due to evidence of particle migration. However, there are definite advantages in treating patients endoscopically. It is evident that the ideal substance should be able to be delivered endoscopically, conserve its volume, and be nonmigratory and nonantigenic. Towards this goal we developed a catheter with an inflatable, detachable and self-sealing silicone balloon that would fit through a 19 gauge cystoscopic needle. Hydroxy-ethyl-methyl acrylate, a hydrophilic polymer that solidifies within 60 minutes after the addition of ferrous sulfate, was chosen as the filling material for the balloon. Conceptually, the sealed balloon would prevent the migration of hydroxy-ethyl-methyl acrylate and the solidified polymer would prevent volume loss. To test this system reflux was created in 6 Hanford mini-pigs by unroofing the ureters bilaterally. In 2 pigs a previously described method of open surgery was used and in the other 4 reflux was created endoscopically using the resectoscope and laparoscopic scissors. The presence of bilateral reflux was confirmed 4 weeks later with a cystogram and the balloon was implanted unilaterally through a cystoscope. The opposite ureter served as an internal control in all animals. A repeat cystogram was performed 2 to 4 weeks after implantation, demonstrating resolution of reflux in the treated side and persistence of reflux in the opposite untreated ureter. Serial cystograms, ultrasound and excretory urography showed no reflux on the implanted side nor any evidence of obstruction. Tissue sections from various organs showed no evidence of particle migration, granuloma formation or inflammatory reaction. Short-term results show that the balloon implants are able to correct reflux without evidence of obstruction. PMID- 1640556 TI - Enterocystoplasty and reflux nephropathy in the canine model. AB - Correction of vesicoureteral reflux at enterocystoplasty is often recommended to prevent the development of reflux nephropathy. Children with enterocystoplasty who require intermittent self-catheterization invariably have asymptomatic bacteriuria. In patients with persistent vesicoureteral reflux after enterocystoplasty the risk of renal damage from this asymptomatic bacteriuria is unknown. Detubularized ileocystoplasty was performed in 17 dogs with either direct nontunneled reimplantation or unroofing of the intramural tunnel and incision of the ipsilateral hemitrigone to create vesicoureteral reflux. Fluoroscopic urodynamic studies were performed 1 month later and unilateral vesicoureteral reflux was present in 6 dogs. All animals had low intravesical pressure and excretory urograms were performed to exclude obstruction. The 6 dogs with reflux were euthanized 3 months postoperatively and the kidneys were examined for histological evidence of pyelonephritis. In 5 of 6 dogs bacterial bladder colonization and subsequent renal pelvic colonization developed on the side of the vesicoureteral reflux. All of these animals had histological evidence of pyelonephritis in the refluxing kidney, whereas only 1 of 6 nonrefluxing control kidneys had any evidence of pyelonephritis (p = 0.031). Our results suggest that vesicoureteral reflux in association with enterocystoplasty leads to chronic upper tract infection and pyelonephritis in a majority of animals, despite creation of a low pressure urinary reservoir. Correction of vesicoureteral reflux at enterocystoplasty should be considered to prevent upper tract damage. PMID- 1640557 TI - Pyelonephritis in male infants: how important is the foreskin? AB - We investigated the association of the uncircumcised foreskin and pyelonephritis in male infants less than 6 months old. During a 21-month prospective study 94 children (age range 2 weeks to 18.9 years) were hospitalized for febrile urinary tract infection. The male-to-female ratio for 35 patients less than 6 months old was 2.2:1. Of 59 patients older than 6 months the male-to-female ratio was reversed at 0.25:1 (p less than 0.001). In 13 of 24 infants (54%) less than 6 months old and in 8 of 12 boys (67%) older than 6 months a dimercaptosuccinic acid renal scan documented acute parenchymal damage (p = 0.72). Vesicoureteral reflux or other genitourinary abnormalities were found in only 3 of 24 patients (12.5%) less than 6 months old compared with 6 of 12 boys (50%) older than 6 months (p = 0.036). Of 24 infants less than 6 months old 22 (92%) were uncircumcised compared with 6 of 12 boys (50%) older than 6 months (p = 0.009). We then retrospectively compared the circumcision status of the infants who had febrile urinary tract infection with a control group of 63 infants matched for age, race and socioeconomic status hospitalized with febrile upper respiratory infection during a similar period. The frequency of uncircumcised infants in the control group with febrile upper respiratory infection was only 44% (28 of 63) compared with 91% of infants with febrile urinary tract infection (p less than 0.001). Overall the findings of the male predominance among patients less than 6 months old with febrile urinary tract infection, the disproportionately high frequency of infants with febrile urinary tract infection who were not circumcised, and the disproportionately low occurrence of vesicoureteral reflux and other genitourinary abnormalities in infants with febrile urinary tract infection strongly support an association between circumcision status and the risk for febrile urinary tract infection and pyelonephritis in male infants. PMID- 1640558 TI - Recombinant human tumor necrosis factor enhances radiosensitivity and improves animal survival in murine neuroblastoma. AB - An analysis of the potential of recombinant human tumor necrosis factor to enhance the radiosensitivity of C1300 murine neuroblastoma was undertaken. Female A/J mice bearing C1300 murine neuroblastoma (right hindlimb) underwent the following treatments: group 1-0.25 cc normal saline intraperitoneally times 2, group 2-0.5 mcg./gm. recombinant human tumor necrosis factor intraperitoneally times 2, group 3-400 cGy. right hindlimb, group 4-800 cGy. right hindlimb, group 5-400 cGy. right hindlimb plus 0.5 mcg./gm. recombinant human tumor necrosis factor intraperitoneally times 2 and group 6-800 cGy. right hindlimb plus 0.5 mcg./gm. recombinant human tumor necrosis factor intraperitoneally times 2. All animals were followed for 21 days after treatment initiation with interval measurements of tumor volume. All single modality treatments were more effective than normal saline in reducing average tumor volumes during the study period (800 cGy. equals recombinant human tumor necrosis factor greater than 400 cGy. greater than normal saline). The addition of recombinant human tumor necrosis factor to radiotherapy moderately augmented antitumor response at radiation doses of 400 cGy. but marked enhancement was attained at radiation doses of 800 cGy. (p less than 0.02). This enhancement was achieved without increased animal morbidity or mortality. Animals receiving recombinant human tumor necrosis factor in addition to 800 cGy. demonstrated increased survival when compared with animals receiving 800 cGy. alone (p less than 0.02). Although statistical synergy was not proved, recombinant human tumor necrosis factor appears to augment significantly radiation-induced tumor regression at no toxic cost to the animal. PMID- 1640559 TI - Prognosis of children with solitary kidney after unilateral nephrectomy. AB - The clinical course of 138 children who underwent unilateral nephrectomy and had a normal contralateral kidney at the time of nephrectomy was reviewed. The diagnosis leading to nephrectomy included obstructive uropathy in 46% of the cases, reflux or pyelonephritis in 30%, Wilms tumor in 15%, hypertension in 4%, dysplastic kidney in 2% and trauma in 2%. Mean age at nephrectomy was 7.3 years and median followup was 24.7 years. Of the 138 patients 121 (88%) are well and 17 died, including 14 secondary to metastatic Wilms tumor and 1 of renal failure. Survival of nonWilms tumor patients was similar to that of an age-matched control group. In 30 patients 24-hour creatinine clearance and 24-hour urinary protein excretion were measured. Proteinuria (greater than 150 mg./24 hours) was found in 8 of the 30 patients (27%) (p less than 0.001), renal insufficiency developed in 9 (30%) (p less than 0.0001) and hypertension occurred in 10% (p greater than 0.10). Children with an acquired solitary kidney are at increased risk for proteinuria and renal insufficiency. PMID- 1640560 TI - Characterization of the upper urinary tract anatomy in the Danforth spontaneous murine mutation. AB - Absence or maldevelopment of the ureteral bud is thought to represent the final pathophysiological pathway resulting in renal anomalies ranging from agenesis to duplication. Little is known about the events preceding anomalous or absent ureteral bud formation. We describe the renal and ureteral anomalies found in a spontaneous murine mutation associated with a short tail: the Danforth or Sd mutation. Thirteen heterozygous pairs of mice were mated. Of 57 near-term progeny 40 had short tails. Microdissection revealed both kidneys and ureters in 35%, neither kidneys nor ureters in 27.5%, absence of the left kidney and ureter in 10%, absence of the right kidney and ureter in 7.5%, and absence of 1 or both kidneys associated with a blind-ending ureter in 20% of the mice. Scanning electron microscopy of gestational day 12 fetuses revealed unilateral or bilateral absence of the metanephros in some embryos, including some with a ureteral bud. Thus, primary absence of the metanephros may have a role in renal agenesis. Additional findings suggest that compensatory renal hypertrophy occurs in utero in the fetuses with unilateral renal agenesis. The morphological abnormalities involving the kidneys in the Sd mutation may represent an excellent model to study the pathophysiology of renal agenesis and mechanisms of normal renal development. PMID- 1640561 TI - A surgical model for normotensive chronic renal failure in the growing piglet. AB - Studying the effects of chronic uremia in children has been hindered by the lack of a suitable large mammalian animal model with normotensive renal failure. We performed nephrectomy with simultaneous contralateral partial nephrectomy using a stapling device and absorbable staples in 22 domestic piglets. Up to 93% of the total renal mass could be excised by this method. A chronic uremic state was reproducibly developed and correlated with the percentage of renal mass excised. There were no associated postoperative complications with the stapled partial nephrectomy. Pigs with moderate renal failure had a significant decrease in growth compared to those with mild renal failure, which represents the successful development of a normotensive large mammalian animal model that could be used to study the effects of chronic renal failure and hyperfiltration during a state of rapid growth. In addition, this study confirms the successful use of a stapling device to perform partial nephrectomy. PMID- 1640562 TI - Fetal nephrotoxicity. AB - Investigation of fetal nephrotoxicity by maternally administered nephrotoxins is hampered by many constraints, including the maternal effects of the nephrotoxin, the ability of the nephrotoxin to cross the placenta and the difficulties associated with direct fetal intervention. In the pouch young of the North American opossum, Didelphis virginiana, we describe the toxic effects of a heavy metal on the immature metanephric kidneys. Varying doses of uranyl nitrate, a heavy metal salt, were administered to opossum pups in the pouch approximately 20 days after birth and the kidneys were harvested 3 to 12 days later for histological analysis. Group 1 consisted of 4 untreated and 5 saline treated pups. Group 2 (9 pups) received 10 to 15 mg./kg. intraperitoneal uranyl nitrate. Group 3 (6 pups) were given a uranyl nitrate dose of 25 mg./kg. Group 4, the high dose group, received either 58 mg./kg. (3 pups) or 87 mg./kg. (3 pups) of intraperitoneal uranyl nitrate. Group 1 kidneys demonstrated no pathological changes except for some mild renal tubular vacuolization seen in the saline treated animals. In group 2 tubular dilatation and necrosis were present 3 days after treatment; tubular regeneration could be seen by day 7. In group 3 glomerular cystic changes, interstitial fibrosis and tubular regeneration were present by day 7. Some restoration of normal architecture occurred by day 12 with fibrosis apparent. Group 4 animals demonstrated much more pronounced cystic changes of glomeruli and tubules as early as day 5 with marked interstitial fibrosis and prominent tubular regeneration. By day 12 group 4 pups continued to demonstrate significant and severe glomerular and tubular cystic changes with marked interstitial fibrosis. Inflammation, although present in all groups (except control), was never prominent. This first description of the effect of heavy metal toxicity on the immature metanephric kidney could provide an insight into the mechanisms of disordered kidney growth. PMID- 1640563 TI - Transfusion medicine faces time of major 'challenges and changes'. PMID- 1640564 TI - As the blood supply gets safer, experts still call for ways to reduce the need for transfusions. PMID- 1640565 TI - Recommendations seek to prevent pressure sores. PMID- 1640566 TI - From the Centers for Disease Control. Accessibility of cigarettes to youths aged 12-17. PMID- 1640567 TI - From the Centers for Disease Control. Scalping incidents involving hay balers- New York. PMID- 1640569 TI - From the Centers for Disease Control. Human rabies--California, 1992. PMID- 1640568 TI - From the Centers for Disease Control. Spina bifida incidence at birth--United States. PMID- 1640570 TI - From the Centers for Disease Control. Acquired immunodeficiency syndrome--1991. PMID- 1640571 TI - From the Centers for Disease Control. Penicillin-resistant pneumococcal disease- Spain. PMID- 1640572 TI - Pregnancy after embryo biopsy and coamplification of DNA from X and Y chromosomes. PMID- 1640573 TI - Surgical standby for coronary balloon angioplasty. AB - OBJECTIVE: To assess the predictability of need for emergency surgery after coronary balloon angioplasty. DESIGN: Nonrandomized intervention study. SETTING: Nonprofit university hospital. PATIENTS: Prior to balloon angioplasty, 1000 consecutive patients were assigned to either the "standby" group (189 patients [19%]) or the "no-standby" group (811 patients [81%]). Patients in the standby group (intervention coordinated with cardiac surgery) included all operable patients undergoing angioplasty of their largest coronary arteries that were not currently or previously totally occluded or collateralized; the no-standby group consisted of the remainder of patients. INTERVENTION: Allocation to coronary angioplasty with or without surgical standby. MAIN OUTCOME MEASURES: Need for bypass surgery, occurrence of myocardial infarction, and mortality from complications of angioplasty. RESULTS: Bypass surgery immediately after angioplasty was done in one patient in each group (standby, 0.5%, vs no-standby, 0.1%). The frequency of infarction was 5% vs 4%, respectively. All eight deaths occurred in the no-standby group (1.0%), but none of them were consequences of a lack of surgical standby. They occurred in situations in which bypass surgery would not have changed the outcome (two cardiac failures late after technically successful angioplasty for postinfarct cardiogenic shock, one in-laboratory rupture of an unrecognized ventricular pseudoaneurysm, and one protamine reaction), secondary to acute problems late after successful angioplasty (two sudden deaths and one vessel occlusion in an inoperable patient), or despite surgery (one patient with left main stem dissection). CONCLUSIONS: Performing roughly 80% of coronary angioplasties without surgical standby did not increase patient risk. Coronary angioplasty without surgical backup, albeit not an ideal setting, appears ethically feasible in selected patients if dictated by logistic considerations. PMID- 1640574 TI - Hip fractures and fluoridation in Utah's elderly population. AB - OBJECTIVE: To test the effect of water fluoridated to 1 ppm on the incidence of hip fractures in the elderly. DESIGN: Ecological cohort. SETTING: The incidence of femoral neck fractures in patients 65 years of age or older was compared in three communities in Utah, one with and two without water fluoridated to 1 ppm. PATIENTS: All patients with hip fractures who were 65 years of age and older over a 7-year period in the three communities, excluding (1) those with revisions of hip fractures, (2) those in whom the hip fracture was anything but a first diagnosis, (3) those in whom metastatic disease was present, or (4) those in whom the fracture was a second fracture (n = 246). OUTCOME MEASURE: Rate of hospital discharge for hip fracture. RESULTS: The relative risk for hip fracture for women in the fluoridated area was 1.27 (95% confidence interval [CI] = 1.08 to 1.46) and for men was 1.41 (95% CI = 1.00 to 1.81) relative to the nonfluoridated areas. CONCLUSIONS: We found a small but significant increase in the risk of hip fracture in both men and women exposed to artificial fluoridation at 1 ppm, suggesting that low levels of fluoride may increase the risk of hip fracture in the elderly. PMID- 1640575 TI - Protection from environmental tobacco smoke in California. The case for a smoke free workplace. AB - OBJECTIVE: To determine the extent of exposure of nonsmoking indoor workers to environmental tobacco smoke (ETS) according to type of work-site smoking policy, work area, workplace size, and demographic characteristics. DESIGN AND PARTICIPANTS: Participants included 7162 adult, nonsmoking, indoor workers who were interviewed as part of the 1990 California Tobacco Survey. Respondents were asked whether anyone had smoked in their work area within the past 2 weeks. RESULTS: An estimated 2.2 million California nonsmokers were exposed to tobacco smoke at indoor work sites in 1990. Nonsmoker exposure to ETS was 9.3% for those working in a smoke-free worksite, 23.2% for those working where there was only a work-area restriction, 46.7% for those working where there was a policy that did not include the work area, and 51.4% for those working where there was no work site smoking policy. After adjustment for type of work area (eg, office, open area), workplace size, and demographic factors, it was determined that nonsmokers working where there was only a work-area ban were 2.8 times more likely to be exposed to ETS than those working in a smoke-free work site. In workplaces with no policy or a policy not covering the work area, nonsmokers were over eight times more likely to be exposed to ETS than those who worked in a smoke-free work site. Nonsmokers who were 18 to 24 years of age, male, or Hispanic, and those with less than a high school education had more exposure to ETS. CONCLUSION: These results indicate that adequate protection of nonsmokers from ETS exposure requires a smoke-free work site. PMID- 1640576 TI - Trends in mortality, morbidity, and risk factor levels for stroke from 1960 through 1990. The Minnesota Heart Survey. AB - OBJECTIVE: The Minnesota Heart Survey is a population-based study designed to monitor and explain trends in cardiovascular mortality, morbidity, and risk factors. DESIGN: Surveillance time-trends study. METHODS: The following trends were examined among men and women aged 25 to 74 years living in Minneapolis-St Paul, Minn: (1) stroke mortality from 1960 through 1990; (2) risk factors in population-based surveys conducted in 1973 through 1974, 1980 through 1982, and 1985 through 1987; and (3) morbidity in a 50% sample of hospitalized discharges for acute-stroke in 1970, 1980, and 1985. RESULTS: Stroke mortality in Minneapolis-St Paul declined slowly from 1960 through 1972 (average fall, 2.4% per year), dropped sharply from 1972 through 1984 (average fall, 6.5% per year), but exhibited little change thereafter (average fall, 1.5% per year). The average level of cardiovascular disease risk factors fell from 1973-1974 to 1985-1987, with the exception of body mass index. In particular, hypertension diagnosis, treatment, and control levels improved substantially between 1973-1974 and 1980 1982, although there was little improvement after 1980-1982. While discharge rates for hospital-coded acute stroke declined substantially between 1970 and 1985 in both sexes, no clear trend was observed in definite stroke rates as validated using standard clinical criteria. Twenty-eight-day case fatality rates of definite stroke improved significantly from 1970 to 1985. CONCLUSIONS: The substantial decline in stroke mortality of more than 50% from 1960 through 1990 appears to have been attributable to both primary and secondary prevention. These data suggest that the long decline in stroke mortality and morbidity in Minneapolis-St Paul has plateaued, although improved detection of stroke with computed tomography prevents an unequivocal conclusion. PMID- 1640577 TI - Elementary school students' performance with two ELISA test systems. AB - OBJECTIVE: To examine analytic performance by previously untrained and inexperienced subjects using enzyme-linked immunosorbent assay (ELISA) tests developed for decentralized laboratories. Performance variability between tests assigned to the "simple" and "moderately complex" Health Care Financing Administration laboratory levels was evaluated. DESIGN: A nonrandomized trial of the Surecell Strep-A chorionic gonadotropin ELISA tests. Each subject processed nine unknown specimens (three negative, three weakly positive, and three strongly positive) for each ELISA test. Subjects were blinded to expected test results. SETTING: An elementary school. SUBJECTS: A convenience sample of 52 students enrolled in the sixth and seventh grades. This age group was chosen because of their ability to generally comprehend instructions and remain attentive to the testing task. INTERVENTIONS: Subjects were either self-trained by reading package insert directions or trained by a manufacturer's sales representative. MAIN OUTCOME MEASURES: Performance was measured as the percentage of correct test results for the unknown specimens. The sensitivity and specificity for each test by operator group were calculated. RESULTS: Subjects demonstrated an overall sensitivity of 97.1% and specificity of 94.7% for human chorionic gonadotropin unknown specimens and a 95.9% sensitivity and 96.8% specificity for group A streptococcus unknown specimens. No significant differences between the self trained group and the representative-trained group were observed for either group A streptococcus or human chorionic gonadotropin tests. Performance was so high with the first specimen that improvement over time (ie, a "learning curve") could not be demonstrated. CONCLUSION: These ELISA test systems are able to achieve high levels of performance by subjects with no formal laboratory background, no previous method specific experience, and limited self-training. PMID- 1640578 TI - Drug allergy. PMID- 1640579 TI - Single-source financing systems. A solution for the United States? AB - Although tax-based and social insurance-based forms of single-source financing differ in how they raise funds, they share a common set of structural characteristics. In particular, they both enable publicly accountable authorities to control aggregate expenditure levels by creating a countervailing power to pressures for increased expenditures from providers. While major reform initiatives are under way in European single-source financing systems, these initiatives have so far sought to improve the efficiency, effectiveness, and/or responsiveness to patterns of service delivery without reducing their commitment to universal access to necessary care. The article concludes with a review of the advantages and disadvantages that could accompany the introduction of a single source financing system in the United States. PMID- 1640580 TI - Coronary angioplasty. Is surgical standby needed? PMID- 1640581 TI - 'Please pass the roach poison' again. PMID- 1640582 TI - Cigarette advertising and corporate responsibility. PMID- 1640583 TI - Cumulative trauma disorders of the upper extremities. PMID- 1640584 TI - The AMA and the Physicians Committee for Responsible Medicine. PMID- 1640585 TI - The resurgence of measles and herd immunity. PMID- 1640586 TI - Informed consent, deception, and discovering drug abuse. PMID- 1640587 TI - The letter from Utrecht. PMID- 1640588 TI - A piece of my mind. Diagnosis: V65.5. PMID- 1640589 TI - Bronchial reactivity: hyporesponsiveness vs hyperresponsiveness. PMID- 1640590 TI - Old age and hemochromatosis. PMID- 1640591 TI - A piece of my mind. Mary-go-round. PMID- 1640592 TI - Frequency, location of cases to be studied. PMID- 1640593 TI - Physicians urged to report moderate to severe immune deficiency cases without evidence of HIV infection. PMID- 1640594 TI - Federal health officials continue to reorganize offices for investigating scientific misconduct. PMID- 1640595 TI - NIH scientists retract published report. PMID- 1640596 TI - From the Alcohol, Drug Abuse, and Mental Health Administration. PMID- 1640598 TI - From the Centers for Disease Control. Sudden infant death syndrome--United States, 1980-1988. PMID- 1640597 TI - From the Centers for Disease Control. Transmission of multidrug-resistant tuberculosis among immunocompromised persons, correctional system--New York, 1991. PMID- 1640599 TI - From the Centers for Disease Control, Cerebrovascular disease mortality and Medicare hospitalization--United States, 1980-1990. PMID- 1640600 TI - From the Centers for Disease Control. Congenital rubella syndrome among the Amish -Pennsylvania, 1991-1992. PMID- 1640601 TI - From the Centers for Disease Control. Shigellosis in child day care centers- Lexington-Fayette County, Kentucky, 1991. PMID- 1640602 TI - From the Centers for Disease Control. Primary amebic meningoencephalitis--North Carolina, 1991. PMID- 1640603 TI - Breast-conserving surgery and radiation therapy: are they underused? PMID- 1640604 TI - Variations in methadone treatment practices. PMID- 1640605 TI - Dads, docs, drugs, and decisions. PMID- 1640606 TI - A widow's grief: the language of the heart. PMID- 1640607 TI - Borrelia burgdorferi in the central nervous system. PMID- 1640608 TI - Borrelia burgdorferi in the central nervous system. PMID- 1640609 TI - Borrelia burgdorferi in the central nervous system. PMID- 1640611 TI - Commercial laboratory testing for chronic fatigue syndrome. PMID- 1640610 TI - Fat content of very low-calorie diets and gallstone formation. PMID- 1640612 TI - American Indians, African Americans: their common histories. PMID- 1640613 TI - Erythema migrans in Lyme disease: a correction. PMID- 1640614 TI - Poor response to rabies vaccination by the intradermal route. PMID- 1640615 TI - A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. AB - OBJECTIVE: To assess prospectively the risk of coronary heart disease associated with elevated plasma levels of homocyst(e)ine. DESIGN: Nested case-control study using prospectively collected blood samples. SETTING: Participants in the Physicians' Health Study. PARTICIPANTS: A total of 14,916 male physicians, aged 40 to 84 years, with no prior myocardial infarction (MI) or stroke provided plasma samples at baseline and were followed up for 5 years. Samples from 271 men who subsequently developed MI were analyzed for homocyst(e)ine levels together with paired controls, matched by age and smoking. MAIN OUTCOME MEASURE: Acute MI or death due to coronary disease. RESULTS: Levels of homocyst(e)ine were higher in cases than in controls (11.1 +/- 4.0 [SD] vs 10.5 +/- 2.8 nmol/mL; P = .03). The difference was attributable to an excess of high values among men who later had MIs. The relative risk for the highest 5% vs the bottom 90% of homocyst(e)ine levels was 3.1 (95% confidence interval, 1.4 to 6.9; P = .005). After additional adjustment for diabetes, hypertension, aspirin assignment, Quetelet's Index, and total/high-density lipoprotein cholesterol, this relative risk was 3.4 (95% confidence interval, 1.3 to 8.8) (P = .01). Thirteen controls and 31 cases (11%) had values above the 95th percentile of the controls. CONCLUSIONS: Moderately high levels of plasma homocyst(e)ine are associated with subsequent risk of MI independent of other coronary risk factors. Because high levels can often be easily treated with vitamin supplements, homocyst(e)ine may be an independent, modifiable risk factor. PMID- 1640616 TI - Maternal heat exposure and neural tube defects. AB - OBJECTIVE: To determine if exposure to hot tub, sauna, fever, or electric blanket during early pregnancy was associated with an increased risk for neural tube defects (NTDs). DESIGN: Prospective follow-up study. SETTING: Mostly private obstetric practices, primarily in New England. PARTICIPANTS: A cohort of 23,491 women having serum alpha-fetoprotein screening or an amniocentesis were identified. Complete exposure and outcome information was available for 97% of these women. OUTCOME MEASURES: Relative risks (RRs) were used to compare incidence of NTD in those exposed to heat with those who were not exposed to any heat. Crude RRs were calculated directly from the data. Unconfounded RRs were calculated using logistic regression. RESULTS: Women reporting any heat exposure (sauna, hot tub, fever, or electric blanket) in early pregnancy had a crude risk of their fetuses developing NTD of 1.6 (95% CI [confidence interval], 0.9 to 2.9). Women reporting exposure to sauna, hot tub, or fever in early pregnancy had a crude risk of their fetuses developing NTD 2.2 times that of women without heat exposure (95% CI, 1.2 to 4.1). For hot tub use, the crude RR was 2.9 (95% CI, 1.4 to 6.3); for sauna, 2.6 (95% CI, 0.7 to 10.1); for fever, 1.9 (95% CI, 0.8 to 4.1); and for electric blanket, 1.2 (95% CI, 0.5 to 2.6). Multivariate adjusted RRs for individual heat sources, after controlling for maternal age, folic acid supplements, family history of NTD, and exposure to other heat sources, were for hot tub use, 2.8 (95% CI, 1.2 to 6.5); sauna, 1.8 (95% CI, 0.4 to 7.9); fever, 1.8 (95% CI, 0.8 to 4.1); and electric blanket, 1.2 (95% CI, 0.5 to 2.6). When only hot tub, sauna, and fever were considered and the women's exposure to each tallied, compared with no heat exposure, the RR for NTDs increased from 1.9 (95% CI, 0.9 to 3.7) after one type of heat exposure to 6.2 (95% CI, 2.2 to 17.2) after two types of heat exposure. CONCLUSIONS: Exposure to heat in the form of hot tub, sauna, or fever in the first trimester of pregnancy was associated with an increased risk for NTDs. Hot tub exposure appeared to have the strongest effect of any single heat exposure. Exposure to electric blanket was not materially associated with increased risk for NTDs. PMID- 1640617 TI - Delayed childbearing and risk of adverse perinatal outcome. A population-based study. AB - OBJECTIVE: To investigate the effect of advancing maternal age on pregnancy outcome among healthy nulliparous women, after adjustment for demographic characteristics, smoking, history of infertility, and other medical conditions. DESIGN: A population-based cohort study was conducted with prospectively collected data from the Swedish Medical Birth Register. PATIENTS: Nulliparous Nordic women (N = 173,715), aged 20 years and above, who delivered single births at Swedish hospitals from 1983 through 1987. OUTCOME MEASURES: Late fetal and early neonatal death rates; rates of very low birth weight (VLBW, less than 1500 g), moderately low birth weight (MLBW, 1500 through 2499 g), very preterm delivery (less than or equal to 32 weeks), moderately preterm delivery (33 through 36 weeks), and small-for-gestational-age (SGA) infants (less than -2 SDs). RESULTS: Compared with women aged 20 to 24 years, women aged 30 to 34 years had significantly higher adjusted odds ratios (ORs) of late fetal deaths (OR = 1.4); VLBW (OR = 1.2); MLBW (OR = 1.4); very preterm birth (OR = 1.2); and SGA infants (OR = 1.4). Among women aged 35 to 39 years, the adjusted OR was significantly higher for VLBW (OR = 1.9); MLBW (OR = 1.7); very preterm birth (OR = 1.7); moderately preterm birth (OR = 1.2); and SGA infants (OR = 1.7). Among women 40 years old and older, the adjusted OR was significantly higher for VLBW (OR = 1.8); MLBW (OR = 2.0); very preterm birth (OR = 1.9); moderately preterm birth (OR = 1.5); and SGA infants (OR = 1.4). CONCLUSIONS: Delayed childbearing is associated with an increased risk of poor pregnancy outcomes after adjustment for maternal complications and other risk factors. PMID- 1640618 TI - Performance of 45 laboratories participating in a proficiency testing program for Lyme disease serology. AB - OBJECTIVE: We show that significant interlaboratory and intralaboratory variations exist in Lyme disease proficiency testing. DESIGN: Six case-defined Lyme serum samples and three serum samples from individuals with no history of Lyme disease were randomized in four shipments and distributed to 45 participating laboratories. RESULTS: Interlaboratory and intralaboratory performances were highly variable. Approximately 4% to 21% of laboratories failed to identify correctly positive serum samples with titers of 512 or more using polyvalent serum or immunoglobulin G conjugates. With lower levels of anti Borrelia burgdorferi antibody in the serum sample, approximately 55% of participating laboratories did not identify a case-defined serum. There was also a striking inability of many laboratories to reproduce their results on split samples from the same individual. In addition, 2% to 7% of laboratories identified serum samples from individuals with no known exposure to B burgdorferi as positive using polyvalent serum. The false positivity rate increased to 27% with the use of immunoglobulin G conjugate. CONCLUSIONS: Our results indicate that there is an urgent need for standardization of current testing methodologies. Until a national commitment is made, serological testing for Lyme disease will be of questionable value for the diagnosis of the disease. PMID- 1640619 TI - Medicare reimbursement accuracy under the prospective payment system, 1985 to 1988. AB - BACKGROUND: Hospital reimbursement by Medicare's prospective payment system depends on accurate identification and coding of inpatients' diagnoses and procedures using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). A previous study showed that 20.8% +/- 0.5% (mean +/- SE) of hospital bills for 1985 contained errors that changed their diagnosis related group (DRG) and that a significant 61.6% +/- 1.3% of errors overreimbursed the hospitals. This DRG "creep" improperly increased net reimbursement by 1.9%, +308 million when projected nationally. The present study updated our previous study with 1988 data. METHODS: The Office of Inspector General, US Department of Health and Human Services, obtained a simple random sample of 2451 hospital charts for Medicare discharges from 1988. The American Medical Record Association reabstracted the ICD-9-CM codes on a blinded basis, grouped them to DRGs, and determined the reasons for discrepancies. RESULTS: Coding errors declined to 14.7% +/- 0.7% in 1988, and a nonsignificant 50.7% +/- 2.6% of DRG errors overreimbursed the hospitals. Projected nationally, hospitals did not receive a significant overreimbursement. Physician misspecification of the narrative diagnoses underreimbursed the hospitals, while billing department resequencing overreimbursed them. CONCLUSIONS: The attestation requirement may have deterred DRG creep due to attending physician upcoding, but the peer review organizations' sentinel effect and educational activities have not eliminated hospital resequencing. PMID- 1640620 TI - The health care quality improvement initiative. A new approach to quality assurance in Medicare. PMID- 1640621 TI - Is syncope related to moderate altitude exposure? AB - STUDY OBJECTIVE: To investigate factors related to syncope occurring on recent ascent to moderate altitude. DESIGN: A 1-year retrospective case-control study, using local acclimatized residents as a control group. SETTING: The two main ambulance destinations for Summit County, Colorado (elevation, 2770 m). PATIENTS: All patients with a diagnosis of syncope, near-syncope, or fainting whose medical records were available for review. RESULTS: There was a significant relationship (P less than .05) between syncope of unknown origin and recent arrival at altitude (less than 24 hours), and a significant inverse relationship (P less than .05) between syncope of unknown origin and arterial oxygen saturation as measured by pulse oximetry. CONCLUSIONS: Short-term exposure to moderate altitude may be related to otherwise unexplained syncope in healthy young adults. We suggest the name high-altitude syncope for this entity and encourage further research in this area. PMID- 1640622 TI - Patient outcomes after lumbar spinal fusions. AB - OBJECTIVES: To determine success and complication rates for lumbar spinal fusion surgery, predictors of good outcomes, and whether fusion improves success rates of laminectomy for specific low back disorders. DATA SOURCES: English-language journal articles published from 1966 through April 1991, identified through MEDLINE searching (spinal fusion plus limiting terms), bibliography review, and expert consultation. STUDY SELECTION: Articles were selected only if they reported at least 1 year of follow-up data enabling the classification of clinical outcomes as satisfactory or unsatisfactory for at least 30 patients. DATA EXTRACTION: Two reviewers independently extracted data on patient characteristics, surgical methods, patient outcomes, and quality of study methods. DATA SYNTHESIS: Of 47 articles, there were no randomized trials. Four nonrandomized studies compared surgery with and without fusion for herniated disks; three found no advantage for fusion. On average, 68% of patients had a satisfactory outcome after fusion, but the range was wide (16% to 95%), and the satisfactory outcome rate was lower in prospective than in retrospective studies. The most frequently reported complications were pseudarthrosis (14%) and chronic pain at the bone graft donor site (9%). Clinical outcomes did not differ by diagnosis or fusion technique, but were worse in studies with a greater number of previously operated patients. CONCLUSIONS: For several low back disorders no advantage has been demonstrated for fusion over surgery without fusion, and complications of fusions are common. Randomized controlled trials are needed to compare fusion, surgery without fusion, and nonsurgical treatments in rigorously defined patient groups. PMID- 1640623 TI - The biology of developmental dyslexia. AB - Dyslexia is a relatively common disorder that, when severe, persists into adulthood. New evidence suggests that females are affected nearly as frequently as males. Neuropsychological studies characterize dyslexia as a language disorder that involves phonological deficits in particular. Educational therapies aimed at direct improvement of reading skill constitute the best available treatment. Variable genetic transmission leading to a final common pathway appears to involve deficits in phonological coding. Postmortem studies and in vivo anatomical imaging suggest altered asymmetry of structures in the temporal lobes, and neuroimaging with positron emission tomography indicates left temporoparietal dysfunction in particular. Neuromaging is providing a window into the brain that promises further insights into the biology of dyslexia. PMID- 1640624 TI - The best health care system in the world? PMID- 1640625 TI - Is the quality cart before the horse? PMID- 1640626 TI - A.S.P.E.N.--a precocious adolescent. PMID- 1640627 TI - Harry M. Vars Research Award. A new model to determine in vivo the relationship between amino acid transmembrane transport and protein kinetics in muscle. AB - The bidirectional transmembrane transport rates of leucine (Leu), valine (Val), phenylalanine (Phe), lysine (Lys), and alanine (Ala) were measured in vivo in the hindlimb muscle of five dogs and related to the rates of protein synthesis and degradation. The compartmental model was based on the systemic continuous infusion of stable isotopic tracers of the amino acids, and the measurement of the enrichment and concentration in the arterial and femoral vein plasma and the intracellular free water in muscle (obtained by biopsy). The transport rate from plasma to tissue (in micromoles per minute) was: Leu, 18.1 +/- 1.8; Val, 26.9 +/- 3.5; Phe, 10.5 +/- 1.6 Lys; 12.2 +/- 1.8; and Ala, 10.7 +/- 3.4. The transport rate from tissue to plasma (in micromoles per minute) was: Leu, 25.5 +/- 2.5; Val, 32.4 +/- 2.8; Phe, 17.0 +/- 2.8; Lys, 24.9 +/- 3.4; Ala, 34.4 +/- 9.0. When the transmembrane transport rate was normalized per unit of amino acid concentration in the source pool, we found that the transport of Leu, Val, and Phe was significantly faster (p less than .05) than the transport of Lys and Ala. The calculated rates of incorporation into hindlimb muscle protein of Phe and Lys (in micromoles per minute) were 4.2 +/- 1.3 and 19.4 +/- 5.3, respectively, and the rates of intracellular appearance from breakdown were 10.7 +/- 1.9 and 32.1 +/- 6.6, respectively. We concluded, therefore, that (1) the transmembrane amino acid transport rate can be measured in vivo in muscle with a relatively noninvasive technique, (2) in the dog hindlimb the equilibration between tissue and plasma free amino acid pool is different for each amino acid depending on the kinetics of the transmembrane transport systems, and (3) the transport rates of amino acids and their rate of appearance from protein breakdown are roughly comparable, suggesting that variations in transport rates could play a role in controlling the rate of protein synthesis. PMID- 1640628 TI - Effect of different dietary triglycerides on liver fatty acids and prostaglandin synthesis by mouse peritoneal cells. AB - The effect of dietary triglycerides varying in fatty acid composition on the tissue fatty acids and prostaglandin synthesis was studied in mice. The dietary fats were medium-chain triglycerides (rich in C8:0 and C10:0), structured lipids (rich in 12:0), high oleic sunflower oil (rich in 18:1), corn oil (rich in n-6 polyunsaturated fatty acids), and menhaden oil (rich in n-3 polyunsaturated fatty acids) fed at 5% by weight in refined diets. The medium chain fatty acids C8 to C12 from medium-chain triglycerides and structured lipids did not accumulate in liver phospholipids. However, long-chain fatty acids from the dietary fats were incorporated into liver lipids, with n-3 polyunsaturated fatty acids replacing arachidonic acid. The synthesis of 6-keto-prostaglandin F1 alpha and prostaglandin E2 by peritoneal cells in response to intraperitoneal injection of zymosan decreased as the arachidonic acid levels were decreased. When the same dietary fats were added to the refined, fat-free diets, at 7.5 wt% levels, together with 2.5 wt% of safflower oil to provide essential fatty acids, only the long-chain fatty acids from the dietary fats were incorporated into the liver lipids. The arachidonic acid in liver lipids was enhanced after supplementation of diets with safflower oil. However, the reduction in prostaglandin synthesis by peritoneal cells in response to intraperitoneal injection of zymosan was similar to that observed when 5% fat was fed. The data suggest that dietary fats of defined composition, with or without added essential fatty acids, may be useful as alternate fat sources in parenteral nutrition in reducing inflammatory responses mediated via prostaglandins. PMID- 1640629 TI - Home parenteral nutrition--a 3-year analysis of clinical and laboratory monitoring. AB - We report a 3-year analysis (1986 to 1989) of the management of 63 home parenteral nutrition patients, 40 with short-bowel syndrome and 23 with chronic intestinal obstruction with or without intestinal resection. Intravenous fluid requirements varied from 0.9 to 6 L/day, and the content of glucose varied between 46 and 531 g/day, protein varied from .0 to 85 g/day, fat from .0 to 100 g/day, sodium from 37 to 695 mEq/day, potassium from 30 to 220 mEq/day, chloride from 60 to 760 mEq/day, and acetate from 0 to 200 mEq/day. Body weight was normalized and well maintained in the majority of patients, but using the strict definition of deficiency as the presence of one abnormal value during 3 years, more than half had abnormal plasma chloride, glucose, alkaline phosphatase, serum glutamic oxaloacetic transaminase, total protein, albumin, selenium, and iron concentrations, and more than a third had low calcium, magnesium, vitamin D, and vitamin C levels. Normochromic anemia was seen in 73% and high blood creatinine associated with low urine volumes in 42%. Most (78%) returned to relatively normal lifestyles, but employability was occasionally impaired by loss of third party insurance coverage resulting from a therapy that may cost $100,000 per year. Overall mortality was low (5% per year), but 73% needed readmission to hospital, mainly for suspected catheter sepsis. The results indicate that home parenteral nutrition has allowed many patients to survive gut failure and return to work but problems with chronic fluid, electrolyte and micronutrient deficiencies, catheter sepsis, and insurance coverage often restrict optimal rehabilitation. PMID- 1640630 TI - Absence of hypermetabolism after operation in the newborn infant. AB - This study was designed to assess the effect of operative stress on resting energy expenditure (REE) in the newborn infant. In 13 neonates who had an uncomplicated abdominal, thoracic, or spinal operation, REE was measured both preoperatively and on the third postoperative day. The mean preoperative REE of 43.19 +/- 7.95 kcal/kg per day was not significantly different from the mean postoperative REE of 41.70 +/- 7.94 kcal/kg per day. Sixteen neonates had REE measured on the first, second, and seventh postoperative days. The mean postoperative REE values of 43.12 +/- 6.92, 42.41 +/- 7.58, and 46.33 +/- 6.89 kcal/kg per day at 1, 2, and 7 days, respectively, were not significantly different from the preoperative REE. There was no significant difference in oxygen consumption, carbon dioxide production, and respiratory quotient between the preoperative and postoperative groups. In this study, an uncomplicated operation did not increase REE in the neonate. PMID- 1640631 TI - Differentiating subtypes (hypoalbuminemic vs marasmic) of protein-calorie malnutrition: incidence and clinical significance in a university hospital setting. AB - Clinical nutrition assessment has identified two types of protein-calorie malnutrition (PCM), a stress-induced hypoalbuminemic form (HAF-PCM) and a marasmic form (MF-PCM) generated by adaptation to starvation. This study evaluated the differences between these two patterns of PCM with regard to precipitating factors and the clinical sequelae of mortality, cost of total parenteral nutrition, length of hospitalization, and rate of sepsis and nosocomial infection. Of 220 patients receiving total parenteral nutrition over a 12-month period (0.7% of 30, 127 admissions), 180 were included in this study. HAF-PCM was diagnosed in 45% and MF-PCM in 25% of study patients. HAF-PCM was more common in older age groups. Women had PCM less often than did men (57% vs 83%), but whereas men developed both forms of PCM equally, women were more likely to develop HAF-PCM. Prolonged mechanical ventilation increased the likelihood of both patterns, whereas the presence of malignancy, concomitant organ failure, trauma, burns, or surgery did not increase the likelihood of developing either pattern of PCM. HAF-PCM increased the length of hospitalization by 29% and the cost of total parenteral nutrition by 42%. The presence of HAF-PCM increased four fold the odds of dying, and the odds of developing nosocomial infection and sepsis almost 2.5 times above that seen in its absence. MF-PCM had no clinical effect of its own on any of the outcome parameters, but instead exerted only an interactive synergistic effect with HAF-PCM on length of hospitalization and cost of total parenteral nutrition. PMID- 1640632 TI - Short-term dietary lipid manipulation does not affect survival in two models of murine sepsis. AB - Dietary lipid manipulation has been shown to have various effects on the immune system, depending on the amount of fat, degree of saturation, and type of fat used. In this study we investigated the role of different sources of fat at different levels on the survival of mice in two models of peritonitis, one with Pseudomonas aeruginosa and the other with Salmonella typhimurium. CF1 mice were pair-fed diets with 5% or 40% of total calories as fat. The source of fat used was coconut oil, oleic acid, safflower oil, or fish oil. Three other diets were tested as well, one with no fat, one with only 0.5% of total calories linoleic acid as the only source of fat, and a control diet that had 12% of total calories as corn oil. At the end of 2 weeks of feeding the experimental diets, mice were challenged with Ps aeruginosa intraperitoneally and mortality was recorded over 1 week. After 3 weeks of feeding the experimental diets, mice were challenged with S typhimurium and mortality was recorded over 2 weeks. No significant differences were seen on survival among groups fed different levels of fat, as well as different sources of fat. We conclude that, overall, 2- and 3-week manipulation of dietary fat does not affect outcome from infection in these models. PMID- 1640633 TI - Liver test alterations with total parenteral nutrition and nutritional status. AB - Liver test abnormalities are a well-recognized complication in the parenterally fed population. Numerous etiologies for the development of elevated liver tests have been suggested. However, the etiology and clinical significance remain unclear. The aim of this retrospective study was to determine the extent of liver associated test (LAT) abnormalities in patients receiving total parenteral nutrition (TPN) and to investigate whether the composition of TPN solutions and the magnitude of malnutrition could be used to predict subsequent LAT abnormalities. Medical records of 78 adult patients who received TPN for at least 2 weeks were reviewed. All subjects had normal LAT results before TPN, were not receiving hepatotoxic drugs, and had no underlying liver disease. Aspartate aminotransferase peaked transiently during week 2 and returned to normal during week 4. Alkaline phosphatase and total bilirubin peaked during weeks 4 and 3, respectively. The average nonprotein kilocalorie distribution was approximately 80% dextrose and 20% lipid. Caloric intake ranged from 7% to 23% above estimated needs. The mean nutritional status score was 22 +/- 15, with a possible range of 0 to 75 (0 indicates no malnutrition). The composition of TPN solutions was not significantly associated with the changes in the three LATs during any week of the 4-week study. The nutritional status score was significantly associated (p less than .05) with the change in alkaline phosphatase during week 1. This study confirms that LAT abnormalities occur during TPN, but the composition of the solution has no significant ability to predict subsequent LAT abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640634 TI - Adaptation to a fish oil diet before inducing sepsis in rats prevents fatty infiltration of the liver. AB - Hypertriglyceridemia and fatty liver are common lipid abnormalities associated with Gram-negative sepsis. Fish oils have been shown to have beneficial effects in reducing plasma triglycerides (TG). This study was designed to investigate whether fish oils would prevent the elevation of plasma TG and the accumulation of liver lipids during sepsis. One group of rats was fed a 10% menhaden oil diet and the other group was fed a 10% corn oil diet for 14 days. On the 14th day, sepsis was induced by injecting the rats with 8 x 10(7) live Escherichia coli colonies/100 g of body weight and the rats were fasted for 22 hours. The liver composition of total lipids and TG in the septic rats prefed the fish oil was lower than in the septic rats prefed the corn oil. In the rats adapted to the corn oil diet, lipids accumulated in the livers of the septic rats in comparison with the control rats. Hepatocytes isolated from the septic rats adapted to the corn oil diet showed an increased esterification of [1-14C]palmitate into TG and phospholipids than hepatocytes from the control rats. Feeding the fish oil diet instead of the corn oil diet before inducing sepsis reduced TG, cholesterol, and phospholipid synthesis by 58%, 79%, and 71%, respectively. The rise in TG synthesis in the septic rats prefed the corn oil diet was associated with an 89% increase in the activity of phosphatidate phosphohydrolase. There was no significant difference in the activities of glycerol-3-phosphate acyltransferase and phosphatidate phosphohydrolase between control and septic rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640635 TI - Measurement of resting energy expenditure in patients with chronic obstructive pulmonary disease in a clinical setting. AB - There is a growing tendency to estimate energy requirements by means of the assessment of resting energy expenditure (REE) by indirect calorimetry. In this study a computerized open-circuit ventilated hood system is described that was constructed for assessing REE in a clinical setting. Measurement error of the device, tested by ethanol combustion was +2% for VO2 and VCO2 and less than 1% for respiratory quotient. To assess the within-patient variability of REE measurements performed in a daily clinical routine, we studied the following aspects of the measurements in several groups of patients with chronic obstructive pulmonary disease: (1) reproducibility, (2) the influence of routine physical activities before the measurement, (3) measurement duration, and (4) difference between measurements using a ventilated hood or a mouthpiece. Reproducibility of measurements with a 2-month interval in 12 weight-stable patients was good (1415 +/- 128 and 1398 +/- 138 kcal/day). Variations due to limited activities and different measurement durations (between 10 and 30 minutes) were not significant. Variations between measurements with a mouthpiece and ventilated hood were larger in patients than in healthy control subjects, but for both groups no systematic difference was established. REE can be assessed reliably by short-term measurements with a ventilated hood in stable chronic obstructive pulmonary disease patients on an outpatient basis, provided a short rest is taken before the measurement. PMID- 1640636 TI - Retrograde (ascending) bacterial contamination of enteral diet administration systems. AB - A prospective clinical study in three phases was performed to determine whether it was possible that enteral diet containers could become contaminated as a result of endogenous organisms ascending retrogradely from the enteral feeding tube via the giving set, and if this did occur whether the incidence could be altered by modifying enteral delivery systems. Each phase observed patients on enteral feeding over a 48-hour study period (phase I, n = 18; phase II, n = 17; phase III, n = 18). Each patient was prescribed an enteral diet of 2 L/24 h administered by continuous pump infusion from a closed 1-L sterile diet container. Four containers were used for each patient, and one giving set was used in the 48-hour period. Diet samples were taken at 12-hour intervals: two from the giving set before and after flushing with residual diet, and one from the diet container. Phases differed only in the design of the giving set: phase I had no drip chamber, phase II had a drip chamber, phase III had a drip chamber and an anti-reflux ball valve at the distal end. Both phase I and III had greater numbers of giving set samples colonized at 24, 36, and 48 hours. In phase I, 3 of 14 sterile diet containers were colonized with greater than 10(4) colony-forming organisms/mL of diet at 48 hours. Only phase II had no organisms contaminating the containers at 48 hours. We conclude that the retrograde spread of organisms from patient to sterile diet container does occur in clinical practice, and that a drip chamber in the giving set may prevent the problem.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640637 TI - Safety and efficacy of glycerol and amino acids in combination with lipid emulsion for peripheral parenteral nutrition support. AB - The safety and efficacy of administering lipid emulsion with ProcalAmine, a glycerol-based parenteral nutrition solution, for peripheral nutrition has not been previously studied. Thirty-four patients recovering from major trauma or surgery were studied while receiving a peripheral parenteral nutrition regimen of either ProcalAmine with 10% lipid emulsion (group 1) or ProcalAmine with 20% lipid emulsion (group 2) for up to 5 days postinjury. Daily dose was 45 mL/kg ProcalAmine, providing 1.35 g of amino acids/kg and 1.35 g of glycero/kg, and 500 mL/day lipid emulsion. The mean daily nitrogen balance was -0.3 g/day in group 1 and -4.1 g/day in group 2. There was no progressive accumulation of circulating glycerol, and urinary glycerol excretion was minimal (less than 0.2 g/day), indicating effective utilization of glycerol as an energy substrate. Our finding that nitrogen balance was better with 10% fat emulsion suggests a limitation in fat utilization in this setting. Both regimens were well tolerated; there were no adverse clinical reactions and no occurrences of phlebitis in either group. PMID- 1640638 TI - Full protein alimentation and nitrogen equilibrium in a renal failure patient treated with continuous hemodiafiltration: a case report of 67 days of continuous hemodiafiltration. AB - Standard care for patients with renal failure while in an intensive care unit involves traditional hemodialysis or peritoneal dialysis and protein restriction. We present a case of a patient with renal failure supported with continuous arteriovenous hemofiltration with dialysis (CAVH-D) who was given full protein alimentation. Total daily urea clearance was measured from the CAVH-D output. Protein load was 196 +/- 34 g/day while receiving total parenteral nutrition and 164 +/- 30 g/day while receiving enteral alimentation. Serum blood urea nitrogen was controlled between 40 and 75 mg/dL, except during septic episodes. Nitrogen balance was estimated based upon known alimentation protein load and measurable and estimated nitrogenous losses. The patient was potentially in nitrogen equilibrium during most of the dialysis period. The cumulative nitrogen balance was positive by 5.2 g after 67 days of dialysis. Volume of alimentation was 3.49 +/- 0.7 liters/day. With CAVH-D, the renal failure patient can receive full alimentation without volume or protein load limitations. Furthermore, nitrogen balances can be estimated easily while the patient is on CAVH-D. PMID- 1640639 TI - Cuff Cath: an initial experience of cuffed polyurethane central venous catheters in children. AB - The tendency of medium- and long-term silicone central venous catheters (CVCs) to block, fracture, and become displaced has led to the evaluation of a polyurethane CVC, Cuff Cath (Viggo Spectramed, Swindon, Wilts, United Kingdom) as a possible alternative because polyurethane is smoother and stronger. We report the first prospective study of polyurethane cuffed CVCs in children. Sixty Cuff Caths were placed in 53 children, mean age 4.7 years (range, 4 days to 16.3 years), mean weight 15.6 kg (range, 3.1 to 58 kg). All CVCs were tunnelled (mean tunnel length, 12 cm; range, 5 to 20 cm) and inserted either into the subclavian vein (n = 28) or internal jugular vein (n = 32). In a total of 6363 catheter days (mean, 111 days per patient; range, 15 to 364 days), three (5%) CVCs had to be removed because of sepsis and one (2%) because of blockage. All other Cuff Caths remained patent to infusion and blood sampling. No Cuff Caths were pulled or fell out, fractured, or migrated. This study demonstrates significant advantages of polyurethane compared with previous series using silicone CVCs with respect to blockage, fragmentation, and dislodgement. A prospective, randomized, controlled trial of Cuff Cath compared with a silicone CVCs in children is required. PMID- 1640640 TI - Parenteral nutrition-related bone disease. AB - Parenteral nutrition (PN)-related bone disease remains a problem in patients of all ages. Understanding of the pathogenesis of PN-related bone disease is complicated by the effect of underlying illnesses, therapeutic interventions, and pre-existing nutrition deficiencies before the initiation of PN therapy. Interrelation of various nutrients, for example, calcium, phosphorus, and vitamin D, in their effects on bone mineralization, demands simultaneous assessment of the role of multiple nutrients and increases the difficulty in defining the role of a single nutrient in the development of bone disease. However, recent reports indicate that there exist a number of factors important in the development of PN related bone disease and some factors such as increased mineral requirement are unique to growing infants whereas other factors such as aluminum toxicity may be common to both adult and pediatric populations. Nonnutritional factors, including chronic use of potent loop diuretics and altered acid-base status, can affect urine mineral loss, cell metabolism, and bone mineralization, particularly in small, preterm infants. Current evidence indicates that the cause of PN-related bone disease is multifactorial, and the prevention of PN-related bone disease awaits better delineation of the exact sequence of pathogenic events. PMID- 1640641 TI - Feeding jejunostomy for post operative nutritional support. PMID- 1640642 TI - Jejunal mucosal injury and restitution: role of hydrolytic products of food digestion. PMID- 1640643 TI - Depressed gut absorptive capacity early after trauma-hemorrhagic shock. PMID- 1640644 TI - Pathogenesis of hepatic steatosis. PMID- 1640645 TI - Nutrition-related bone disease. PMID- 1640646 TI - Resting energy expenditure in liver disease. PMID- 1640647 TI - Fatty acid-sensitive acid phosphatase activity of tubercle bacilli. AB - In a whole cell assay system with p-nitrophenyl phosphate as substrate, strains of Mycobacterium tuberculosis and M. bovis were identical in the pH-activity pattern of acid phosphatase. It was a one-peak curve with a pH optimum at 6.2 and sharp symmetrical slopes. The enzymatic activity did not reflect the virulence. When the cells were subjected to mechanical fractionation, the major part of the enzymatic activity was found in a particulate fraction and a minor portion in supernatant and cell walls, suggesting the location of the enzyme in the membrane. Exposure of the cells to free long-chain fatty acids, especially unsaturated ones, reduced the enzymatic activity in a dose-response manner with concomitant decrease in the viability. However, no causal relationship between these two effects was suggested from the collateral experiments. PMID- 1640648 TI - Different susceptibilities to attenuated poliovirus of cynomolgus monkeys from the Philippines and other Southeast Asian countries. AB - Susceptibilities to attenuated poliovirus of cynomolgus monkeys were assessed by the intraspinal inoculation method with the same single bulk lot as the reference for each of the three poliovirus types. The lesion-inducing virus dose in the spinal cord of 50% of monkeys inoculated (LID50) varied widely from 10(6.4) to lower than 10(2.5), the difference being as much as 10,000-fold, depending on the birth place of the monkey. The birth places of the monkeys used were traced and categorized into the following three districts; the peninsular region, Indonesia and the Philippines. The LID50 value of the attenuated poliovirus in the monkeys from the Philippines were much lower than those in the monkeys from the other two districts. PMID- 1640649 TI - [Platelet accumulation in abdominal aortic aneurysms and the effect of antiplatelet drugs: assessment by indium platelet scintigraphy]. AB - A dual tracer technique using 111In labeled platelets and 99mTc labeled human serum albumin was applied to evaluate the in vivo thrombogenicity in 12 cases with abdominal aortic aneurysm (AAA) and the effect of antiplatelet drug on the thrombogenicity. The magnitude of platelet accumulation at AAA was expressed as the ratio of radioactivity of 111In platelets on the vascular wall to those in the blood pool (PAI; platelet accumulation index). Of the 12 patients with AAA, 11 had positive studies on baseline imaging and 1 had equivocally positive image. The PAI value (Mean +/- SD) over the AAA was 53.8 +/- 34.1% as compared to -8.6 +/- 4.4% in the control group (p less than 0.01). Seven patients with an AAA and positive baseline images were restudied during platelet active drug with 325 mg of aspirin. During treatment with aspirin, of 7 patients, 5 had positive images, of which 3 were decreased and others unchanged compared to baseline studies, 1 equivocally positive one and one negative one. The PAI value during treatment (21.9 +/- 18.6%) was significantly decreased compared to those in baseline study (52.1 +/- 23.9%). Our results suggest that the method used for platelet imaging in the present study may be useful for studying the in vivo thrombogenicity and the effect of platelet active drugs in AAA. PMID- 1640650 TI - [Clinical evaluation of 99mTc ethyl cysteinate dimer SPECT in patients with spinocerebellar degeneration; comparison with cerebral blood flow determined by PET]. AB - Technetium-99m ethyl cysteinate dimer (99mTc-ECD) is regarded as a promising radiopharmaceutical for imaging regional cerebral blood flow (rCBF). We evaluated 99mTc-ECD SPECT comparing with rCBF images obtained by PET in 12 patients with spinocerebellar degeneration (SCD). SPECT images of 99mTc-ECD demonstrated characteristic findings of decreased rCBF in bilateral cerebellar hemisphere and almost identical with PET rCBF images in all patients based on the visual inspection. Semiquantitative analysis by drawing 14 intracranial regions of interest on SPECT and PET images revealed linear correlation between 99mTc-ECD count and rCBF measured by PET even in relatively high rCBF regions. In summary, 99mTc-ECD is a promising tracer for evaluating rCBF in patients with SCD and distribution of it correlates well with rCBF measured by PET. PMID- 1640651 TI - [Radioisotope therapy of malignant pheochromocytoma with iodine-131 metaiodobenzylguanidine--absorbed dose assessments using SPECT]. AB - The correlation of absorbed doses D (rad) of tumors in 4 patients with malignant pheochromocytoma, who were treated by 131I-MIBG (3.7 GBq), with their clinical courses were analyzed and the clinical significance of determination of absorbed dose was discussed. Absorbed doses of 131I-MIBG in the tumors were measured by using SPECT at the time of therapy. Absorbed dose was calculated based on the MIRD (medical internal radiation dose committee) equation. Tumor volumes were ranged from 17 g-100 g (mean 40 g), effective half lives were ranged from 1.3 days-5.9 days (mean 3.6 days), and tumor absorbed doses were varied between 5.4 Gy-68 Gy (mean 40 Gy). When the absorbed doses of the tumor exceeded over 40 Gy, good clinical responses were obtained. The initial treatment seemed to be important for 131I-MIBG therapy, since the absorbed doses in the following therapy became reduced. These results indicate that the quantitative SPECT for radioisotope therapy is clinically valid and that the calculated absorbed doses correlate well with clinical responses. PMID- 1640652 TI - [Usefulness of vitamin A binding protein as a marker for capillary endothelial permeability]. AB - We performed a preliminary study to assess the usefulness of Vitamin A binding protein (VABP) as a gamma-camera marker for capillary endothelial permeability. We used a guinea pig model of endotoxin (LPS) induced acute lung injury. We calculated the concentration ratio of either 125I-albumin or 125I-VABP in lung tissue to that in plasma (tissue plasma ratio; T/P) as a parameter of capillary endothelial permeability. 99mTc-diethylene triamine pentaacetic acid (DTPA) was used as a marker for pulmonary interstitial volume. We estimated wet to dry lung weight ratio as a parameter of lung water accumulation (W/D). LPS increased the T/P of 125I-albumin and W/D, suggesting the development of permeability edema. The T/P for 125I-VABP was also increased, indicating that 125I-VABP can be used to detect elevated capillary endothelial permeability. In both groups, LPS and saline, the T/P was higher for 125I-VABP than for 125I-albumin. These data suggest that the pulmonary capillary endothelium is more permeable to VABP than albumin. PMID- 1640653 TI - [Evaluation of gastroenterological disease by using 18F-FDG PET--differential diagnosis of malignancy from benignity]. AB - In this study, we used 18F-FDG PET to differentiate gastroenterological malignancy from benignity. We investigated 122 patients with gastroenterological disease before treatment (with lesions exceeding 2.0 cm in diameter only). 60 min after injection of FDG, although 16 cases out of 17 benign disease did not reveal accumulation higher than normal tissue, 105 cases of malignant tumor except some of hepatocellular carcinoma revealed high accumulation of FDG. FDG uptake was expressed as the Ci/Cp ratio, calculated from radioactivity of the tumor (Ci) and the plasma (Cp). 89 cases out of 90 which show more than 2.0 of Ci/Cp ratio were malignant tumor. On the other hand, 32 cases which show less than 2.0 contained 16 cases of benign disease and 15 of hepatocellular carcinoma. FDG PET is a useful tool for differential diagnosis of malignant tumor from benign disease except some of hepatocellular carcinoma. PMID- 1640654 TI - [123I-IMP SPECT study on patients with amnestic syndrome]. AB - Regional cerebral blood flow was studied using single photon emission CT (SPECT) with 123I-IMP to elucidate the pathophysiology of amnesia. Four patients with amnestic syndrome diagnosed by DSM-III-R criteria were investigated. SPECT images demonstrated definite hypoperfusion of the temporoparietal lobe and relative sparing of motor-sensory and occipital cortices in two out of four patients. Since these abnormalities of regional cerebral blood flow have been considered to be characteristic findings in dementia of the Alzheimer type, two patients with temporoparietal hypoperfusion are suggested to manifest the early stage of dementia of the Alzheimer type. Our observations suggest that 123I-IMP SPECT is an useful modality in the diagnosis of the early stage of dementia of the Alzheimer type, especially in patients with only memory impairment. PMID- 1640655 TI - [Property of electrocardiogram gated single photon emission tomography by 99mTc methoxy isobutyl isonitrile]. AB - 99mTc-methoxy isobutyl isonitrile (MIBI) is a new developed myocardial perfusion imaging agent. Because this compound has higher photon energy than thallium (Tl), electrocardiogram gated single photon emission tomography (SPECT): end-diastolic (ED) and end-systolic (ES) short axis (SA) images could be taken. To investigate property of gated MIBI SPECT, MIBI myocardial scintigraphy, Tl scintigraphy (TMS) and analysis of left ventricular wall motion were performed in 6 patients with myocardial infarction. Left ventricle was divided into 8 segments. Perfusion defect (PD) was scored: "0" (normal), "1" (hypo-perfusion), "2" (defect). Wall motion abnormality (WMA) was also scored: "0" (normokinesis), "1" (hypo-kinesis), "2" (a-, dys-kinesis). Severity and extent of PD and WMA were calculated. Severity of WMA was 3.0 +/- 2.0 (M +/- SD), severity of PD was 3.3 +/- 1.7 in TMS, 3.7 +/- 1.3 in no-gated MIBI, 5.0 +/- 0.6 in ES-MIBI, 7.3 +/- 2.0 in ED MIBI. Extent of WMA was 2.3 +/- 1.0. Extent of PD was 2.5 +/- 1.3 in TMS, 3.0 +/- 1.6 in no-gated MIBI, 3.5 +/- 0.8 in ES-MIBI, 4.8 +/- 1.0 in ED-MIBI. Compared with wall motion abnormality, severity and extent of PD in ED-MIBI was larger. From our data, it is concluded that perfusion defect in ED-MIBI was overestimated significantly. When we evaluate gated MIBI image, we must consider this property. PMID- 1640656 TI - [Clinical use of serum erythropoietin determination by the recombigen EPO RIA kit]. AB - Serum erythropoietin (EPO) levels were determined by the recombigen EPO RIA kit (DPC) in normal subjects and patients with renal dysfunction, diabetes mellitus, hypothyroidism and a variety of hematological disorders. Mean (+/- SD) serum EPO levels were 18.6 +/- 5.6 mU/ml in 180 normal subjects and no sex difference was obtained. Serum EPO levels in older subjects were slightly greater than those in younger subjects. There was a negative correlation between serum EPO levels and Ht values in anemic patients with normal renal function, whereas serum EPO levels were within the normal range in anemic patients with renal disorders, suggesting that serum EPO levels were relatively low in patients with chronic renal failure. Serum EPO levels were rather increased in patients with diabetes mellitus and hypothyroidism. High serum EPO levels were obtained in patients with a variety of hematological disorders such as acute leukemia, multiple myeloma, myelodysplasia syndrome, aplastic anemia and pure red cell aplasia. In a patient with pure red cell aplasia treated with glucocorticoids, serum EPO levels were lowered before anemia was recovered and reticulocytes were increased. These findings indicate that measurement of serum EPO levels are useful for not only differential diagnosis of anemia but also clinical evaluation of the treatment. PMID- 1640657 TI - [Three-dimensional display of 99mTc-MIBI myocardial scintigraphy]. AB - One of 99mTc-hexakis, 99mTc-methoxyisobutyl isonitrile (MIBI), has been demonstrated to have a myocardial uptake proportional to regional coronary blood flow. In this study, 99mTc-MIBI myocardial scintigraphy were performed for 16 patients with ischemic heart disease. After injection of 740 MBq of 99mTc-MIBI, 64 projection images were collected during a 360-degree rotation. Three dimensional (3D) display of the left ventricle was reconstructed with depth shading method from 99mTc-MIBI SPECT images, which were reconstructed by filtered back projection method. In 9 of the patients, left ventricular cineangiography were performed as diagnostic gold standard. Four physicians blinded to patients' clinical informations interpreted 3D images and SPECT images on separate occasions. Diagnosis of hypoperfusion by 3D displays agreed with those of SPECT in 92.9% (104/112 segments), and disagreed in 7.1% (8 segments). Sensitivity and specificity of 3D images were 87.0 and 93.9%, which were not statistically different (p less than 0.05) from that of SPECT images (91.3, 97.0%). Receiver operating characteristic (ROC) analysis revealed nearly identical curves for the two. Although 3D display had nearly identical diagnostic ability with SPECT, observers reported that 3D images were easier to diagnose than SPECT images. An advantage of the 3D display is that the display gives a more realistic impression of the left ventricle to an observer than tomography or planar imaging. Another advantage is that 3D display can reduce the amount of data storage compared with that of SPECT. In conclusion, 3D images may be useful for diagnosis of hypoperfusion of left ventricle. PMID- 1640658 TI - Characteristics of the ambulation-increasing effect of the noncompetitive NMDA antagonist MK-801 in mice: assessment by the coadministration with central-acting drugs. AB - Characteristics of the ambulation-increasing effect of MK-801, a non-competitive NMDA antagonist, were assessed through the coadministration of MK-801 with various central-acting drugs in mice. The MK-801 (0.3 mg/kg, i.p.)-induced ambulation-increment with a slight ataxia was maximum at around 50 min, and ambulation returned to the control level at about 3 hr after the administration. At 1 mg/kg, the mouse's activity transiently increased, followed by a decrease due to a marked ataxia, which was due to neither stereotypy nor convulsion, for 20-50 min, and then increased again; the ambulation-increment continued even at 4 hr after the administration. Coadministration of MK-801 (0.3 mg/kg, i.p.) with either methamphetamine (2 mg/kg, s.c.), cocaine (20 mg/kg, s.c.), GBR-12909 (10 mg/kg, i.p.), scopolamine (0.5 mg/kg, s.c.), caffeine (10 mg/kg, s.c.) or morphine (10 mg/kg, s.c.) produced a significant enhancement of the effect. However, 0.1 mg/kg of MK-801 had no effect on the interaction with these drugs. On the other hand, the ambulation-increasing effect of MK-801 (0.3 mg/kg) was significantly reduced by haloperidol (0.3 and 0.1 mg/kg, s.c.), ceruletide (0.01 and 0.1 mg/kg, i.p.), reserpine (0.05 and 2 mg/kg, s.c., pretreatment 4 hr before) and nimodipine (1 and 3 mg/kg, i.p.), but it was scarcely modified by alpha-methyl-p-tyrosine (100 and 200 mg/kg, i.p., pretreatment 24 hr and 4 hr before), imipramine (20 mg/kg, i.p.), 6R-L-erythro-5,6,7,8-tetrahydro-biopterin (100 mg/kg, i.p.), pilocarpine (1 and 4 mg/kg, s.c.), N6-(L-2-phenylisopropyl) adenosine (0.03 and 0.1 mg/kg, s.c.) and naloxone (1 and 5 mg/kg, s.c.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640659 TI - Reversing effect of anti-asthmatic drugs on bronchoconstriction induced by antigen challenge and histamine in anesthetized guinea pigs. AB - We performed an in vivo evaluation of bronchodilation using a model of antigen induced bronchoconstriction in anesthetized guinea pigs pretreated with indomethacin, pyrilamine and propranolol, and the results were compared with those for the histamine-induced response. Test drugs were administered intravenously when the antigen or histamine response reached its peak. Leukotriene (LT) D4 antagonists, FPL55712 and LY171883, gradually reduced the antigen-induced response, whereas the lipoxygenase inhibitor phenidone had no such effect. The bronchodilator theophylline rapidly reduced the antigen-induced response, and the adenylate cyclase activator forskolin had a similar effect. The following drugs also had no effect: nifedipine (calcium-channel antagonist), cromakalim (potassium-channel opener), amlexanox and disodium cromoglycate: DSCG (anti-allergic drugs), OKY-046 (thromboxane A2 synthetase inhibitor), and dapsone (anti-inflammatory drug). Theophylline, the beta-adrenoceptor agonist salbutamol and the histamine H1-blocker pyrilamine had only a small reversing effect on histamine-induced bronchoconstriction. These results suggest that antigen-, but not histamine-, induced bronchoconstriction in anesthetized guinea pigs is a useful in vivo model for evaluating the bronchodilating effect of anti-asthmatic drugs. PMID- 1640660 TI - Suppression by cyclosporin A of anti-GBM nephritis in rats. AB - The suppressive effect of cyclosporin A (CyA) on the development of glomerulonephritis was evaluated in rats with either original- or crescentic-type anti-glomerular basement membrane (GBM) nephritis. CyA (2.5, 10 or 20 mg/kg) was given p.o. daily to original-type anti-GBM nephritic rats for 10 days from the day after the injection of anti-GBM serum. The development of the nephritis was dose-dependently suppressed by CyA before the production of specific antibody against rabbit gamma-globulin (the heterologous phase). In addition, CyA suppressed glomerular infiltration of leukocyte subsets (leukocyte with common antigen, T cell, helper T cell, suppressor/cytotoxic T cell, macrophage/monocyte). CyA was given p.o. daily to crescentic-type anti-GBM nephritic rats for 10 days from the 10th day after the injection of anti-GBM serum. CyA-administration caused a distinct suppression of the deterioration of nephritis during the autologous phase. In addition, CyA markedly suppressed the antibody production. The above data indicate that CyA has a beneficial effect on anti-GBM nephritis, and the antinephritic action of this agent may be due to the inhibition of glomerular infiltration of leukocyte subsets as well as the suppression of the antibody production. PMID- 1640661 TI - A uniform alteration in serum lipid metabolism occurring during inflammation in mice. AB - The present study was designed to delineate changes in serum lipid levels following various kinds of tissue injury or inflammation such as contact sensitivity to picryl chloride, thermal burn, carrageenin-induced edema, the administration of turpentine oil, Freund's complete adjuvant (FCA), killed Bordetella pertussis (BP) or lipopolysaccharide (LPS). A uniform change in the serum lipid metabolism was observed in mice that received these inflammatory stimuli; that is, increases in total cholesterol, free cholesterol and phospholipid levels, a decrease in the ester ratio and a decline in lecithin: cholesterol acyltransferase activity as well as a decrease in albumin levels, which is an index of the acute-phase response. However, serum triglyceride levels were increased by treatment with the bacterial stimuli (FCA, BP and LPS) but decreased by treatment with the other stimuli. The serum free cholesterol and phospholipid levels were significantly correlated with the intensity of contact sensitivity, which was modified by treatment with cyclophosphamide. Indomethacin or dexamethasone suppressed carrageenin-induced edema and inhibited some of the alterations in lipid metabolism that developed during inflammation because each affected a part of the lipid metabolism. These findings suggest that, like the appearance of acute-phase proteins, the uniform change in serum lipid metabolism may be another sensitive index of the acute inflammatory response. PMID- 1640662 TI - Reversal of alpha-methyltyrosine-induced hypoactivity by 6-(R)-5,6,7,8-tetrahydro L-erythrobiopterin (R-THBP) in mice. AB - The effects of peripheral administration of 6-(R)-5,6,7,8-tetrahydro-L erythrobiopterin dihydrochloride (R-THBP), a natural cofactor for tyrosine and tryptophan hydroxylases, were investigated in mice treated with a competitive inhibitor of tyrosine hydroxylase, alpha-methyltyrosine (alpha-MT). A subcutaneous dose of 250 mg/kg of alpha-MT decreased markedly both ambulatory activity and cerebral contents of norepinephrine, dopamine and their metabolites in mice. An intraperitoneal dose of 100 mg/kg of R-THBP, which did not alter ambulatory activities in normal mice, improved the hypoactivity in alpha-MT treated mice. Moreover, R-THBP at intraperitoneal doses of 60 and 100 mg/kg inhibited the impairment of cerebral catecholamine metabolism induced by alpha-MT in mice. We suggest that the reversal of the alpha-MT effects by R-THBP might be due to reactivation of tyrosine hydroxylase in the central nervous system. PMID- 1640663 TI - Assessment of Ca(2+)-antagonistic effect of SM-6586 and its isomers, novel 1,4 dihydropyridine derivatives, by radioligand binding assay. AB - The Ca(2+)-antagonistic effects of the 1,4-dihydropyridine derivative (+/-)SM 6586 and its optical isomers were compared with those of its two derivatives ((+/ )SM-7297 and (+/-)SM-7548) and other Ca(2+)-antagonists using a radioligand binding assay. The Ca(2+)-antagonistic effects of the optical isomers of SM-6586 were in the order of (+) greater than (+/-) greater than (-)SM-6586 in both rat brain and heart. The pKi value of (+)SM-6586 was comparable to those of nimodipine, nicardipine, nifedipine and nitrendipine. The pA2 value for (+)SM 6586 was the highest among the SM-6586 isomers, thus suggesting that (+)SM-6586 has a potent Ca(2+)-antagonistic effect. PMID- 1640664 TI - [Confirmed and borderline hypertension found in 44% of men (aged 40-59 years) working at the H. Cegielski plant in Poznan]. AB - Blood pressure was measured in 3317 men, aged 40-59, working in H. Cegielski Metal Works in Poznan. The average systolic pressure for the whole population was 130.9 mmHg (SE = 17.90). The average diastolic pressure was 83.7 mmHg (SE = 10.03). The systolic, diastolic and mixed systolic-diastolic hypertension was found in 539 men which makes 16.3% of the study group. The borderline systolic hypertension was found in 327 men i.e. 9.9%, borderline diastolic hypertension in 267 men i.e. 8.0%. Both systolic and diastolic borderline hypertension displayed 339 men i.e. 10.2% of the study group. So, borderline hypertension (systolic, diastolic and systolic-diastolic) was found in 933 men which makes 28.1% of the population under the study. PMID- 1640665 TI - [Hypertension, heart failure and angina pectoris. Diurnal rhythm of urinary excretion of catecholamines]. AB - Adrenaline, noradrenaline and dopamine excretion was investigated in essential hypertension (n = 20), atherosclerotic heart failure (n = 20, NYHA class II and III), chronic angina (n = 10) and in healthy controls, in four time intervals: between 600-1200, 1200-1800, 1800-2400, 2400-600. Fluorimetric method of Anton and Sayre was employed. In patients with essential hypertension the circadian rhythm of adrenaline, noradrenaline and dopamine excretion was maintained but in all time intervals excretion of dopamine was decreased. In individuals with congestive heart failure due to atherosclerosis and in patients with ischemic heart disease, physiological circadian rhythm of adrenaline and noradrenaline excretion was found to be abolished. This was not the case with dopamine excretion which was undisturbed. PMID- 1640666 TI - [Tetralogy of Fallot. Physical work capacity after its total correction]. AB - Results of exercise tests in 21 children after total correction of Fallot tetralogy (mean 5 years after surgery) are reviewed. Maximal exercise capacity recalculated for body mass and for total body area was approximately 60% of normal values. Maximal heart rate was lower than among healthy children. There was no statistical correlation between exercise capacity nad age while operated, nor time after surgery. PMID- 1640667 TI - [Long QT syndrome after organophosphate insecticide poisoning]. AB - A case of prolonged QT syndrome (PQTS) caused by unintentional poisoning with organic phosphate pesticides is reported in a 73 year old farmer. PQTS developed and coexisted with other symptoms of poisoning such as low levels of cholinesterase, vomitus, diarrhoea, miosis, hypersalivation and occurred with typical symptoms. Despite concomitant with PQTS advanced ventricular extrasystoles the most dangerous form of them--ventricular tachycardia "torsades de pointes"--wasn't observed what was attributed among other things to scrupulous control and replenishment of potassium++ and magnesium and avoidance of typical antiarhytmic drugs in ventricular arrhythmia+ treatment. Acquired (most often after drug treatment, toxic and resulting from electrolytic disturbances) forms of PQTS are discussed stressing their heterogeneity and necessity of preventive treatment (different, dependent on etiology). PMID- 1640668 TI - [Cardiac rupture and tamponade in a pregnant woman with acute myocardial infarction]. AB - A case is described of a 35-year old pregnant woman (38-th week, tertigravida) with an acute myocardial infarction (AMI). The diagnosis of anterolateral myocardial infarction was based on the clinical, biochemical, ecg and echocardiographical findings. Ventricular premature beats were observed in the tenth day of AMI: Delivery was accomplished by cesarean section without complications. In the second day after the cesarean section the patient died. On autopsy cardiac rupture, tamponade and fresh necrosis of the lateral wall was found. PMID- 1640669 TI - [Combined heart defects: tetralogy of Fallot, common atrium and a single atrioventricular valve diagnosed by echocardiography]. AB - We present a case of the rare coincidence of three mechanisms leading to development of congenital heart disease in intrauterine life: intrinsic defect of the development of the cardiac loop (dextrocardia), failure of normal expansion of the subpulmonary infundibulum (Fallot syndrome) and endocardial cushion defect (common atrium and common atrioventricular valve ). It was associated with partial viscera inversion. A 31-year old man with congenital cyanotic heart disease, and Blalock-Taussig anastomosis was admitted to the hospital due to symptoms of severe cardiac failure. On physical examination: systolic murmur, hepatomegaly, ascites, leg's edema and cyanosis were found. In ECG--atrial fibrillation with 3-d degree a-v block. Standard echocardiography revealed: dextrocardia, a large single atrium with ostia of pulmonary and systemic veins, single atrio-ventricular valve , large ventricular, Fallot-like septal defect. The papillary muscles were not visible in the left ventricle. Aorta and pulmonary trunk arose from morphological right ventricle. The patient died on the 3-rd day of hospitalization in the course of cardiac and respiratory insufficiency. Postmorten examination confirmed the diagnosis. PMID- 1640670 TI - [Stenosis of the main trunk of the left coronary artery]. PMID- 1640671 TI - [Emergency treatment of arterial hypertension]. PMID- 1640672 TI - [Does fish consumption prevent arteriosclerosis?]. PMID- 1640673 TI - [More about aspirin in cardiology]. PMID- 1640674 TI - [Polymer ocular implants for controlled release of drugs. I. Animal testing of the materials]. AB - Presented are the results of trials with hydrogel inserts received by radiation method and applied into the conjunctival sac of rabbits. In the future they can serve for incorporation of some definite drugs. PMID- 1640675 TI - [Polymer ocular implants with controlled release of drugs. II. Preliminary testing of implants with incorporated pilocarpine]. PMID- 1640676 TI - [Vitreous body proteins. IV. Proteolytic activity of the vitreous body in pathological conditions of the eye]. AB - Two groups of proteins are present in the vitreous: collagen and non-collagen, deriving probably from the blood serum. The authors examined the proteolytic activity against haemoglobin in the course of some ocular pathological conditions. It was demonstrated that the vitreous digests haemoglobin in the acid division of pH (optimum--3.0-4.5) with various activity dependent on the pathological condition of the eye. PMID- 1640677 TI - [Parasitic uveitis in children]. AB - Seven children with an atypical parasitic uveitis were treated in the Department of Ophthalmology in Bialystok in the period 1985-1989. Parasitic background had been discovered in all the children: toxocara in 3, lambliasis in 2 and nematodiasis also in 2. Specific treatment achieved an improvement of the visual acuity and the inflammatory process abated. PMID- 1640678 TI - [Glaucoma in lens capsule pseudoexfoliation syndrome]. AB - The authors observed 27 patients (39 eyes) with glaucoma in the course of the pseudoexfoliation of the lens capsule syndrome treated in the period of 1979 1989. In all the patients the corneo-scleral angle was open with a considerable amount of pigment; 30 eyes exhibited opacification of the lens. The conservative anti-glaucomatous treatment was successful in only 2 patients. Control of the IOP was attained in 5 eyes after a laser trabeculoplasty and in 23 eyes after the Elliot-Fronimopoulos goniotrepanation. Discussed was the lesion of the visual function occurring in the presented syndrome. PMID- 1640679 TI - [Prognosis of the development of pathological conditions in open-angle glaucoma]. AB - The authors prepared a matrix of probability of transition for each of the stages of the disease between the particular years of observation of such characteristics as: the visual acuity, visual field, intraocular pressure and the condition of the lens in 435 persons (854 eyes) with simple glaucoma. The greatest probability of an unchanged condition of the optic nerve and a normal visual field at the onset of treatment (0.45 and 0.74). For the severely damaged eyes the indexes amount respectively 0.07 and 0.34. PMID- 1640680 TI - [Analysis of the results of the treatment of patients with open-angle glaucoma]. AB - Evaluated were the results of a conservative and surgical treatment in 478 patients (870 eyes) after 5 and 10 years of observation. Taken into the account were: the visual acuity, visual field and the condition of the lens. The comparison of results of the conservative and surgical treatment showed that better results had been obtained in eyes treated surgically. The visual field did not indicated any statistically essential differences at any stage of observation. Much more advanced deterioration of the visual acuity was revealed in surgically treated eyes; this was probably caused by a progressive opacification of the lens. PMID- 1640681 TI - [Clinical evaluation of Ocuflur]. AB - Presented is the initial clinical evaluation of Ocuflur, a compound of Allergan. The influence of the drug on the size of the pupil and the reaction of the pupil to a light flash was tested in volunteer subjects. The efficacy of the drug was tested intraoperatively. PMID- 1640682 TI - [Cronassial in the treatment of neuropathies and atrophy of the optic nerve]. AB - The study presents the evaluation of treatment by Cronassial of 26 patients including 16 with post-inflammatory optic atrophy, 4 with optic neuritis and 6 multiple sclerosis patients with optic neuropathy. One half of the patients showed an improvement of the visual acuity and visual field, and small improvement of the visual evoked potentials. No improvement of the conductivity of the impulses of the retino-cortical potentials has been observed. The best efficacy of the compound has been seen in the inflammatory conditions of the optic nerve. PMID- 1640683 TI - [Results of the treatment of ocular toxoplasmosis in personal experience]. AB - Ocular toxoplasmosis manifested itself in following clinical forms: as central serous chorioretinitis, pars planitis, iritis, intrabulbar neuritis and central retinal degeneration. The diagnosis was based on the clinical picture, serological examinations, the course of the disease and the effect of the specific treatment. The authors used piridimide++ compounds, sulfonamides, steroids, folic acid and Tavegyl, Decaris as well as photo-coagulation. The efficacy of all these methods was compared. PMID- 1640684 TI - [Effect of complex treatment of retinitis pigmentosa on the results of pupillography]. AB - Presented are the results of a 3 years long observation of the pupillary reaction in patients with pigmentary retinal dystrophy who have been subjected to a complex treatment. The authors discovered a consistency between the changes in the visual field and the amplitude of the pupillary reaction. PMID- 1640685 TI - [Peripheral photocoagulation of the retina in the treatment of early forms of diabetic retinopathy]. AB - The authors present the results of a 5 years long observation of patients with an early form of diabetic retinopathy in whom one performed a photocoagulation of the retinal periphery. They observed the behavior of the visual function and the changes in the anterior chamber angle. PMID- 1640686 TI - [The role of vitrectomy in the treatment of retinal detachment with macular holes]. AB - The authors discuss the pathogenesis and the method of treatment of a retinal detachment with a macular hole basing on personal material and a review of foreign literature. Personal material consists of 11 eyes in 10 patients operated upon in the University Ophthalmic Department in Munich in the period November 1988--April 1990. In all the cases the primary method of treatment based on vitrectomy performed through the pars plana with a gas tamponade. In 4 cases a reoperation with silicon oil tamponade was necessary. Anatomical reattachment of the retina was achieved in 9 among 11 treated eyes. In 10 cases the visual acuity was 1/50 or better. Five among them showed the visual acuity at last 0.1. PMID- 1640687 TI - [Practical instructions for removal of ferromagnetic foreign bodies from the eye]. AB - On basis of a several-years expertise in surgical extraction of ferromagnetic intraocular foreign bodies the authors are analysing the exact localization, the isoelectric magnetic lines and the position of the electromagnet. They present the most favourable method of a successful intervention in the course of the first extraction without causing any damage to the intraocular structures. PMID- 1640688 TI - [Use of the Foucault's test for determining the contrast sensitivity of the visual system]. AB - The authors present the thesis that in apperception of the Foucault's test in condition of a threshold contrast only the first harmonic component is decisive; in connection with this one can replace the sinusoidal tests applied for the demarcation of the sensitivity curve of the visual system to contrast by Foucault's test. They point to the eventual possibility--if the influence of the following components would prove to be essential--of using the Foucault's test together with the sinusoidal test in order to make the diagnosis of pathological conditions more selective. The CSF function was designated by means of the sinusoidal and Foucault's tests seen on a monitor screen using the methods of contrast increase. In 8 subjects observing simultaneously one discovered that for the frequencies larger or equal to 1.5 stop-1 one can apply the Foucault's test instead of the sinusoidal test. Below the space frequency of 1.5 stop-1 one observed differences between the values of sensitivity to contrast demarcated by means of both tests; these differences result probably from the influence of the higher harmonics of the Foucault's test on the apperception of the test. PMID- 1640689 TI - [Glaucoma attacks in Weill-Marchesani syndrome]. AB - Presented is a case of Weill-Marchesani syndrome complicated by acute attacks not responding to conservative treatment. The authors discuss a correct procedure in these cases and indications for a surgical intervention. PMID- 1640690 TI - [X-linked retinitis pigmentosa]. AB - The study presents a case of a family whose members exhibit an X-linked retinal pigment dystrophy. The attention is called to the fact of an early onset of the disease, full development of the symptoms at an young age and a bed prognosis. The clinical characteristic of inheritance in X-linked retinal pigment dystrophy is discussed. PMID- 1640691 TI - Drugs of abuse in saliva: a review. AB - There has been substantial interest in the use of saliva as a diagnostic medium for drugs of abuse because it can be obtained noninvasively. Although drugs of abuse have been investigated in saliva for more than a decade, the role of saliva remains uncertain. A clear picture is difficult to obtain because of variations in (1) the analytical methods used; (2) the dose regimen of subjects, which was either unknown or differed between studies; and (3) the elapsed time between drug intake and sample collection. This communication summarizes the studies on the quantitative determination of different drugs of abuse in saliva to elucidate the current status in this area. Marijuana, cocaine, phencyclidine, opiates, barbiturates, amphetamines, and diazepines (or their metabolites) have all been detected in saliva by various analytical methods, including immunoassay, gas chromatography/mass spectrometry, and thin layer chromatography. Initial studies with cocaine and phencyclidine suggest a correlation between saliva and plasma concentrations of these drugs, indicating a dynamic equilibrium between saliva and blood. Tetrahydrocannabinol, the active component in marijuana, on the other hand, does not appear to be transferred from plasma to saliva. However, tetrahydrocannabinol is sequestered in the buccal cavity during smoking and can be detected in saliva. These findings point to the potential role of saliva in the analysis of many illicit drugs. To clearly identify the role of saliva as a diagnostic medium for drugs of abuse, research efforts should be directed towards (1) performing systematic studies on correlations between saliva, blood, and urine and (2) determining the concentrations of drugs and their metabolites in saliva as a function of dose and time after intake. PMID- 1640692 TI - N,N'-diethyl-m-toluamide (m-DET): analysis of an insect repellent in human urine and serum by high-performance liquid chromatography. AB - A procedure for monitoring m-DET in human urine and serum is described. m-DET is removed from the urine specimen by partitioning into diethyl ether, but solid phase extraction is used to remove it from human serum. The urine and serum m-DET values are determined by HPLC with a UV detector. The limit of detection was 0.09 micrograms/mL in urine and 0.09 micrograms/g for serum. The percent of m-DET recovered from human urine spiked between 0.50 and 8.00 micrograms/mL was 90 +/- 5.4%. For human serum spiked between 0.25 and 10.00, the percent recovered was 96 +/- 5.9%. The pooled relative standard deviations (RSD) for spiked matrices were 0.06 for urine and 0.06 for serum. PMID- 1640693 TI - The detection of danazol and its significance in doping analysis. AB - The use of anabolic steroids and related compounds in sport is forbidden by the International Olympic Committee (IOC). Because danazol (17 alpha-pregna-2,4-dien 20-yno[2,3-D] isoxazol-17 beta-ol) is structurally related to the anabolic steroid stanozolol, its use should be questioned. Therefore, the detection and the significance of danazol in doping analysis are discussed. A urine specimen suspected of containing danazol metabolites was analyzed in order to characterize the metabolites. After isolation and conversion into three different derivatives, the metabolites were subjected to gas chromatography/mass spectrometry (GC/MS) in the electron impact (EI) mode. The structure assignment was based on the molecular ions, fragmentation patterns observed for the three different derivatives, and the possible metabolite structures given in the literature. Ethisterone was identified as a nonconjugated metabolite. 2 Hydroxymethylethisterone was observed in two stereoisomeric forms. One stereoisomer was found mainly in the nonconjugated steroid fraction and the other in the conjugated fraction. The results were confirmed by analyzing urine specimens of a volunteer who was known to have taken danazol. Derivatization methods and GC/MS data are given to implement danazol detection in routine screening and confirmation procedures. PMID- 1640694 TI - Distinguishing sympathomimetic amines from amphetamine and methamphetamine in urine by gas chromatography/mass spectrometry. AB - Derivatives of seven commonly used sympathomimetic amines and two "designer amines" were isolated from urine, separated chromatographically from amphetamine and methamphetamine, and determined by mass spectrometry with selected ion monitoring. The drugs included ephedrine, propylhexedrine, pseudoephedrine, phenylpropanolamine, hydroxynorephedrine, phenylephrine, phentermine, methylenedioxyamphetamine (MDA), and methylenedioxy methamphetamine (MDMA). The drugs were liquid extracted from urine and derivatized by either heptafluorobutyric anhydride (HFBA) or 4-carbethoxyhexafluorobutyryl chloride (4 CB). Because the base peak ions for ephedrine, pseudoephedrine, propylhexedrine, MDMA, and phentermine are identical to methamphetamine (e.g. 254 amu for HFBA) and those for phenylephrine, hydroxynorephedrine, phenylpropanolamine, and MDA are identical to amphetamine (e.g. 240 amu for HFBA), a table of selected ions was developed for all 11 drugs that distinguished amphetamine and methamphetamine from the sympathomimetic amines with either HFBA or 4-CB. The distinguishing ions rely on the ring structure of the different drugs and fragmentation associated with that structure. The 4-CB reagent partially derivatized the hydroxy containing sympathomimetic amines, while the HFBA completely derivatized all the sympathomimetic amines. Furthermore, false positive results for the 4-CB reagent were found only for methamphetamine (20-2250 ng/mL of methamphetamine) when high concentrations (greater than 5 micrograms) of ephedrine or pseudoephedrine were present in the specimen. These results are related to a combination of injection port temperature and cleanliness of the injection port sleeve. PMID- 1640695 TI - Confirmation of a carboxylic acid metabolite of polychlorotrifluoroethylene and a method for its GC-ECD analysis in biological matrices. AB - 3.1 Oil, referred to as polychlorotrifluoroethylene (pCTFE), is a polymeric mixture consisting primarily of trimers and tetramers of chlorotrifluoroethylene (CTFE) end-capped with chlorine. Inhalation studies have associated dose-related body weight loss, increased organ weights, and abnormal hepatic enzyme activities with exposure to pCTFE. The carboxylic acid metabolites of pCTFE have been shown to cause hepatotoxicity in rats, which is manifested by increased liver weights and the proliferation of hepatic peroxisomes. A method was developed to derivatize these carboxylic acid metabolites. Tissue homogenates and feces were extracted with methanol, and urinary metabolites were extracted on octadecylsilane (ODS) solid-phase extraction columns. Aliquots of the extracts and whole blood were methylated with 3N methanolic HCl to transesterify the carboxylic acid metabolites to volatile methyl esters. The pCTFE methyl esters were analyzed by gas chromatography (GC) with electron capture detection (ECD). The on-column limit of detection was 5 pg for each methyl ester. Solid-phase extraction of spiked urine gave extraction efficiencies of 90.4% for the trimer acid and 84.7% for the tetramer acid. This method was successfully applied to toxicity studies in rats and nonhuman primates. The identities of the derivatized metabolites were confirmed by GC/MS. PMID- 1640696 TI - Analysis and identification of azaperone and its metabolites in humans. AB - Azaperone, dihydroazaperone, and 4'[fluoro-4-(4-(2-pyridyl)-1 piperazinyl]butyrophenone are identified in the urine of an intoxicated patient. The structures of the metabolites were confirmed by comparison of their TLC, GC, and GC/MS data with those of synthesized materials. PMID- 1640697 TI - Analysis of spleen specimens for carbon monoxide. AB - Crucial to the investigation of aircraft fatalities is the analysis of biological specimens for carbon monoxide (CO). In many cases, blood specimens are unavailable or unsuitable for analysis, and the testing of an alternate specimen for CO becomes necessary. Spleen specimens provide a rich source of red blood cells and hence can be a primary substitute for blood. To verify this, 40 paired blood and spleen specimens were analyzed for CO by using a gas chromatographic method. Ten specimens with a spleen CO saturation level (sat.) of less than 10% were associated with corresponding blood specimens with CO sat. less than 10%. Fifteen of the 18 spleen specimens with CO sat. greater than 29% were associated with blood specimens with greater than 48% sat. Results were inconclusive when the spleen CO sat. was between 10 and 29%. We concluded that spleen CO sat. can reflect blood CO sat. in certain situations, particularly when spleen CO sat. is high. PMID- 1640698 TI - Immunoassay method validation for a modified EMIT phencyclidine assay. AB - Immunoassay drug testing methods, that have been modified from the manufacturers' recommended procedure to be used for the analysis of federally regulated specimens or other forensic samples require evaluation to ensure their scientific validity. These validation studies must demonstrate the accuracy, precision, and linearity of the modified immunoassay around the cutoff concentration, substantiate adequate rate separation, and verify the ability of the assay to differentiate positive and negative samples. Modification of the EMIT d.a.u. phencyclidine assay in order to achieve the federally mandated cutoff concentration of 25 ng/mL is common. This study describes the validation of a modified EMIT phencyclidine assay and a protocol that allows for the evaluation of similarly modified immunoassays. PMID- 1640699 TI - Clozapine tissue concentrations following an apparent suicidal overdose of Clozaril. AB - Clozapine is a tricyclic dibenzodiazepine derivative that is classified as an "atypical" antipsychotic drug. A 25-year-old male was brought to a hospital emergency room following the ingestion of an estimated 20 100-mg tablets of clozapine. After several hours in the hospital, the patient died. The cause of death was listed as acute clozapine intoxication. It was also noted upon autopsy that the patient had an unusual eosinophilic myocarditis. The toxicological and pathological findings are presented in this report. PMID- 1640700 TI - Distribution of isoniazid in an overdose death. AB - A fatality due to the ingestion of isoniazid, a tuberculostatic agent, is presented. Isoniazid was extracted by a single step extraction procedure, derivatized with trifluoroacetic anhydride, and identified and quantified by gas chromatography/mass spectrometry (GC/MS). The distribution of isoniazid was as follows: heart blood 43 mg/L, subclavian blood 94 mg/L, urine 470 mg/L, bile 900 mg/L, liver 650 mg/Kg, kidney 110 mg/Kg, and stomach contents 4 mg. PMID- 1640701 TI - Evaluation of reagent strips for the rapid diagnosis of nitrite poisoning. AB - Two commercial urine test strips based on the Griess nitrite-specific diazonium salt reaction, having sulfanilamide and para-arsanilic acid as substrates, respectively, were studied as qualitative tests in the rapid diagnosis of nitrite/nitrate poisoning. Their usefulness was compared to other rapid tests, such as the sulfanilic acid-1 naphthylamin and diphenylamine blue tests. The practical sensitivity limit to nitrites in plasma and in water of both the reagent strips and SA-1NA test was 0.50 micrograms NO2/mL, while the diphenylamine test, which is not nitrite specific, showed a positive reaction to nitrites in plasma and in water above 50 micrograms NO2/mL and 5 micrograms NO2/mL, respectively. The in vitro assays were evaluated in vivo by the sublethal intoxication of a sheep with nitrite, demonstrating that commercial urine test strips may be useful for the rapid diagnosis of nitrite/nitrate poisoning. PMID- 1640702 TI - Surgical complications of intraoperative radiation therapy: the Radiation Therapy Oncology Group experience. AB - Intraoperative radiotherapy (IORT) is being used with increasing frequency in many institutions in the United States but little is known about the surgical complication rates. The Radiation Therapy Oncology Group initiated three prospective studies in IORT in 1986 and we report here the experience in advanced malignancies of the stomach, pancreas, and rectum. The incidence and nature of major surgical complications were reviewed and presented with their implications in regard to future IORT trials. Two hundred twenty-seven patients were entered on three studies by 20 participating institutions between 1985 and 1989. One hundred twenty-nine patients received IORT while 98 patients were found to have too advanced disease to be benefited by IORT and underwent palliative surgical procedures only. IORT doses ranged from 12-22 Gy and bowel anastomoses were not irradiated. Wound infection in the IORT group was 6% vs. 2% in the non-IORT patients but this was not significant at the P = 0.05 level. Other complications included anastomotic leak (n = 5), operative bleeding (n = 10), pancreatitis (n = 2), and were not statistically different in the IORT and non-IORT groups. The mortality rate for the IORT and non-IORT groups combined was 1.8%. This large multi-institutional experience in patients with advanced malignancy demonstrates that patients receiving IORT do not have a higher surgical complication rate than those not receiving IORT. Long-term survival data await the implementation of Phase III trials in advanced intra-abdominal malignancy. PMID- 1640703 TI - Retroperitoneal surgery in patients with nonseminomatous testicular cancer and minimal residual tumor. AB - In the period 1980-1991, 78 patients with advanced nonseminomatous testicular cancer underwent retroperitoneal lymphadenectomy for post-chemotherapy residual masses less than 2 cm. To decrease the frequency of "dry ejaculation" in these patients with no or limited residual disease, the extent of dissection was reduced during the period, with bilateral dissections (49 cases, 1980-1986) being initially replaced by unilateral procedures (19 cases, 1983-1990) and subsequently by nerve-sparing techniques (10 cases, 1990-1991). As expected, a higher total number of lymph nodes was found in the retroperitoneal specimens after bilateral (44 (13-100)) than after unilateral (21 (7-35)) and nerve-sparing (18 (7-60)) procedures. The number of lymph nodes with pathological changes was low, with 3 (1-16) after bilateral, 2 (1-9) after unilateral, and 2 (1-4) after nerve-sparing operations. Histological examination revealed only necrosis/fibrosis in 65% of the patients, elements of mature teratoma in 28%, and remnants of viable malignant tumor in 6%. There were no major postoperative complications. "Dry ejaculation" was reported by 84% of the patients with bilateral operations, but was generally avoided after the unilateral (16%) and nerve-sparing (nil) procedures. After a mean follow-up of 83 (5-138) months, 6 patients have developed a recurrence, only one of them primarily in the retroperitoneal space. It is concluded that in patients with minimal residual retroperitoneal tumor, postchemotherapy lymphadenectomy using a unilateral or nerve-sparing technique seems to offer an effective therapeutic alternative with acceptable postoperative morbidity and preserved ejaculation. PMID- 1640704 TI - Postoperative atrial fibrillation in cancer surgery: preoperative risks and clinical outcome. AB - Postoperative atrial fibrillation (AF) is a recognized complication of cancer surgery. The purpose of this study was to define preoperative risk factors for AF, and to evaluate the clinical significance of the arrhythmia. We reviewed the medical records of 43 patients with postoperative AF admitted to the surgical intensive care unit (SICU). All patients were older than 60 years, 79% had a history of cigarette smoking, and 44% had hypertension. AF occurred an average of 2.8 days following surgery, and lasted an average of 2.1 days. No significant complications developed, and there were no long-term sequelae. This study suggests that, in cancer patients, postoperative AF is a disease of elderly patients. In addition the arrhythmia appears to be a relatively transient and benign phenomenon. Prolonged monitoring in an intensive care setting may not be necessary for asymptomatic, hemodynamically stable patients. PMID- 1640705 TI - Regional DNA content heterogeneity in colonic adenocarcinoma: prognostic significance in patients with liver metastases. AB - We retrospectively examined by flow cytometry the DNA ploidy pattern in tissue blocks from 25 primary colon adenocarcinomas and their lymph node and liver metastases. Intratumoral heterogeneity was present in 22% of primary tumors and 21% of metastatic liver deposits. Intertumoral heterogeneity, measured between the primary tumor and its lymph node and liver metastases, was 0% and 20%, respectively. Of 24 patients who underwent successful resection of their liver metastases, 8 neoplasms had uniformly diploid DNA content, while 16 tumors had aneuploid DNA pattern in either the primary tumor, the metastases, or both. Five year survival was better in the diploid group (38% vs. 7%, P = 0.10 by log rank analysis). Three of eight patients in the diploid group remain free of disease, while all 16 patients with aneuploid cell populations have died of recurrent disease. PMID- 1640706 TI - The hepatic artery--a guide to major upper abdominal resections. PMID- 1640707 TI - Malignant melanoma of the vulva: a clinicopathologic study of 18 cases. AB - In a study of 18 patients diagnosed with vulvar malignant melanoma between 1975 and 1991, the effect of clinical and pathologic variables on the survival was evaluated. The overall 5-year survival rate was 28.6%. In 14 cases the tumor was retrospectively microstaged with use of Breslow depth and Chung levels. International Federation of Gynecology and Obstetrics (FIGO) stage and Breslow depth did not correlate well with survival. Positivity of groin lymph nodes at initial surgery was associated with an insignificant worsening in survival. An inverse correlation, although statistically not significant, was demonstrated between advancing Chung levels and survival. It is concluded that since the data with respect to microstaging of vulvar malignant melanoma is, as yet, still limited, great caution should be used in electing less aggressive surgery than radical vulvectomy and bilateral groin lymphadenectomy for patients with early microstage localized disease. PMID- 1640708 TI - Oncological aspect of immediate breast reconstruction in mastectomy patients. AB - In this study, we compared the relapse-free and overall survival of 83 patients who underwent mastectomy with immediate reconstruction (MIBR) using a musculocutaneous flap with or without silicone implant with those of 153 patients with breast cancer who underwent mastectomy without immediate reconstruction. In univariate analysis, the overall and/or relapse-free survival of reconstructed patients with four or more positive axillary lymph nodes or those with menopausal status were significantly inferior compared with those of nonreconstructed patients. In multivariate analysis, however, the immediate breast reconstruction did not appear to have a significant adverse influence on all patients, and on the subgroups stratified by menopausal status or axillary lymph node metastases. Therefore, it was concluded that MIBR using a musculocutaneous flap did not compromise the survival of patients with breast cancer. PMID- 1640709 TI - The role of fine needle aspiration in the diagnosis of thyroid nodules: analysis of 795 consecutive cases. AB - The utility of fine needle aspiration (FNA) and physical examination for selecting patients with palpable thyroid nodules for surgery was evaluated in 795 consecutive cases. Surgery was performed in 216 patients based upon the cytological diagnosis and clinical criteria. Excluding 42 patients who were lost to follow-up, the remaining 537 were regularly followed up (range, 2-10 years). Cytological findings were classified as malignant, histologic control recommended (suspicious), follicular tumor, benign, and unsatisfactory. Thirty-six aspiration biopsies were positive for malignancy and the diagnosis was confirmed histologically in 34 of them. In 65 patients with final histological diagnosis of malignancy, cytology was positive in 34, suspicious in 20, benign in 3 cases, and unsatisfactory in 8. All patients with cytological diagnosis of follicular tumor had a benign lesion at histology. There were two false positive and three false negative cytological results among the 216 histologically confirmed cases. Excluding unsatisfactory specimen sensitivity, specificity and the predictive value for a positive and a negative result were respectively 95%, 97.5%, 94.5%, and 97%. We conclude that FNA is a very reliable diagnostic test in the evaluation of thyroid nodules and is the best guidance in addition to clinical criteria for selecting patients to be submitted to surgery. PMID- 1640710 TI - Cisplatin plus VP-16 combination chemotherapy in advanced refractory breast cancer. AB - Twenty-nine patients with advanced refractory breast cancer were treated with cisplatin 20 mg/m2/d and VP-16 100 mg/d for 5 days every 3-4 weeks. Ten patients received mitomycin C 10 mg/m2 every 6 weeks additionally. Partial response was obtained in 10 of 26 evaluable patients (38%). The response rates for the group treated with and without mitomycin C were 40% and 37.5%, respectively. Median response duration was 5.5 months in partial responders. Median survival was 9.5 months for partial responders and 2 months for the rest of the patients. Cisplatin and VP-16 combination can be considered as a salvage treatment in heavily pretreated patients with advanced breast cancer. PMID- 1640711 TI - Primary oesophageal carcinoma in teens. AB - Seven teenaged patients with primary oesophageal carcinoma, treated at our hospital in the last 6 years are presented and their management discussed. Five patients had localised disease. Three of them underwent total oesophagectomy, one was given radical radiotherapy, and one was lost to follow-up. Two patients had metastatic disease at presentation. The primary oesophageal carcinoma in this age group may not be so rare as reported in the literature and must be considered in the differential diagnosis of dysphagia. Like their older counterparts, the outcome depends on the stage of the disease and is not influenced by age per se. PMID- 1640712 TI - Prognostic profile for patients with pheochromocytoma derived from clinical and pathological factors and DNA ploidy pattern. AB - Eighty-eight patients with pheochromocytoma and paraganglioma treated over a 28 year period (1960-1987) were studied. Based on clinical course, they were divided into three prognostic groups: benign (n = 57); multiple (n = 12); and metastatic (n = 19). Using clinical data, histopathologic findings, and tumor nuclear DNA content a prognostic profile for each group was constructed. The following variables were studied: age, familial pheochromocytoma, associated endocrine or neoplastic disorders, number and location of the lesion at diagnosis, size of the tumor, and the nuclear DNA ploidy pattern. Of these prognostic factors the most significant to predict a future malignant clinical course were large size and local tumor extension at time of surgery. Family history of pheochromocytoma, associated endocrine disorders, and young age at presentation predicted multiplicity. Old age, absence of familial pheochromocytoma or related endocrine disorders and DNA diploid tumors seem to be favorable findings. Using these variables in combination may be helpful for early identification of patients with malignant, multiple, or benign pheochromocytoma and paraganglioma. PMID- 1640713 TI - A comparison of the clinical characteristics of second primary and single primary sarcoma: a population based study. AB - The clinical characteristics of 240 patients with sarcoma as a second metachronous primary neoplasm (SPN) were compared with those of 8,815 patients with sarcoma as a single tumor. The data were obtained from patients registered during the period 1973-1986 in the Surveillance, Epidemiology and End Results (SEER) Program in the United States. Seventy-four of the 240 SPN patients had postirradiation sarcoma (PIS) while the other 153 patients developed the sarcoma as a second tumor in an area which was not exposed to prior radiotherapy (non PIS). The stage of disease at diagnosis was more advanced in patients with PIS than in those with single sarcomas but the difference did not reach statistical significance. Overall, in comparable clinical stage localized and regional disease there was no statistically significant difference in survival between PIS and non-PIS sarcoma patients after adjusting for age. The survival of patients with localized or regionally advanced sarcoma as a second tumor was significantly worse than of those with single sarcomas with the same stage. There was no difference in survival between first or second sarcomas with metastatic disease. PMID- 1640714 TI - En bloc caudate lobe and partial vena cava resection using a Gott shunt for retrohepatic caval bypass. AB - A technique of retrohepatic inferior vena cava bypass is described, useful for resection of the hepatic caudate lobe. A 77 year old female developed a solitary metastatic tumor mass in the caudate lobe compressing the Inferior Vena Cava (IVC), with cavography showing the IVC to be compressed, but patent. Without evidence of other metastatic disease radical resection of this tumor was performed. Successful resection was accomplished using a Gott shunt and porta hepatus compression for hepatic vascular isolation. No pump was used to avoid heparinization. Postoperative imaging confirmed IVC patency. The serum carcinoembryonic antigen (CEA) level fell to normal and remained so for 18 postoperative months. This introduces a new use of an atriocaval shunt for hepatic isolation during resection. PMID- 1640715 TI - Primary brain lymphoma after X-ray irradiation to the scalp for tinea capitis in childhood. AB - A 39-year-old male developed primary brain lymphoma 33 years after receiving scalp irradiation for tinea capitis. This is the first reported association between cranial irradiation during childhood and subsequent development of primary brain lymphoma. PMID- 1640716 TI - Adenocarcinoma arising within a gastric duplication cyst. AB - A rare case of carcinoma arising within a gastric duplication cyst in a 72 year old woman is presented. This is the oldest patient in whom neoplastic transformation of this usually benign developmental abnormality has been reported. The clinical and pathologic features of this patient are demonstrated and reviewed in the context of prior reported cases. PMID- 1640717 TI - Dynamics aspects of long distance functional interactions between membrane-bound enzymes. AB - The aim of this mini review is to study how an organized charged milieu, such as a membrane, may alter functional long-distance interactions between bound enzymes. Two questions are more specifically considered. The first is to know whether the overall response of a bound enzyme is dependent upon the degree of spatial order of fixed charges and enzymes molecules. The second is to determine whether electric interaction between the fixed charges of the matrix and the charged substrate may generate hysteresis loop of substrate concentration as well as oscillations of this concentration at the surface of the membranes. These effects that have been shown to occur at the surface of membranes, are not the result of intrinsic properties of enzymes. They appear as the consequence of the interplay between functional long-distance interactions between bound enzyme systems and electric repulsion effects of mobile ions. They may be viewed as supramolecular devices that allow storing information from the external milieu. PMID- 1640718 TI - Polynuclear ions in aluminum toxicity. PMID- 1640719 TI - Shape and length of myosin heads. AB - There is controversy concerning the shape and length of myosin heads. In the present paper we try to analyse the data and to draw clear conclusions in this field. When the myosin heads are isolated (S1) from the rest of the molecule, their length is approximately 12 nm and their shape is close to that of a prolate ellipsoid with an axial ratio approximately 2.3 (in solution) or close to that of a comma when attached to F-actin (with a length of 12-13 nm). When the myosin heads are observed on a whole molecule, their length is approximately 19 nm and they are pear-shaped. Here we suggest that all these observations are compatible. We believe that, for a whole myosin molecule, a large part of the head-rod joint (S1/S2 joint) is measured with the head, owing to a particularly heavy staining or shadowing of this joint. On the other hand, S1 is probably built up of a head part plus the S1/S2 joint, which is not revealed by the usual techniques (hydrodynamics, X-ray and neutron scattering). Finally, the comma shape would be related to a flexible part in the head region of S1, which is significantly bent when S1 is attached to F-actin, but which would be less bent for S1 in solution. A similar bending also occurs in crystalline S1. PMID- 1640720 TI - A model of heat-induced clonogenic cell death. AB - When cells are exposed to elevated temperatures, clonogenicity decreases in a temperature-dependent manner displaying non-linear kinetics. In this report we show that the survival of synchronized cell populations after heat exposure can be characterized by a parameter epsilon, which is normally-distributed throughout the population. Cells whose corresponding epsilon-value lies below an arbitrary threshold value epsilon min are unable to form a colony. Upon transfer of a cell culture to an elevated temperature, the mean value of the epsilon distribution decreases exponentially over time with a rate dependent upon the difference between the current and final mean value, until reaching a final value epsilon f dependent on the particular temperature used, thus representing a larger proportion of cells with epsilon less than epsilon min which are non-clonogenic. The analyses evaluate a temperature-independent parameter k which is presumed to be dependent upon the growth conditions of the cell population, and a temperature dependent parameter epsilon f, which is characteristic of the new temperature perturbed steady state. Comparison of the results of analysis of synchronized G1 cell survival data to that for S phase cells obtained over a range of temperatures shows that it is sufficient to ascribe the increased thermal sensitivity of S phase cells to a different k value, the temperature-dependence of epsilon f being identical in the two cases. Linear regression analysis of the temperature-dependence of epsilon f, when expressed as 1n (-epsilon f) = a0 + a1/T demonstrated strong linearity (r2 = 0.99) for either the individual (G1 or S) or combined data sets. This description of heat-induced cytotoxicity may be of use as the basis for a dose concept for the clinical administration of hyperthermia. PMID- 1640721 TI - A mathematical model of the mechanism of vertebrate somitic segmentation. AB - A mathematical model for the mechanism of periodic pattern formation in the process of somitogenesis is proposed. It is assumed that the metameric arrangement first appears before somite formation at the stage of transition of mesodermal cells into a polarized state. The model is based on the assumption that besides the mechanism of contact cell polarization there exists a mechanism of polarization suppression due to excretion of some chemical substance by polarized cells. Periodicity appears as a result of interaction of a kinematic wave of somitogenic cell determination with the cell cycles of mesodermal cells. PMID- 1640722 TI - A bifurcating autoregression model for cell lineages with variable generation means. AB - The bifurcating autoregression model for cell lineage data is extended to allow for observations whose means vary from generation to generation. The maximum likelihood estimates of this extended model are found and used to estimate the generation means and overall variance. The model is also used to test for inherited effects as measured by mother-daughter correlation, and for environmental effects as measured by the sister-sister correlation, conditional on inherited effects. Applications to data sets on EMT6 cells and Escherichia coli are given. PMID- 1640723 TI - The continuous Sir Philip Sidney game: a simple model of biological signalling. AB - An analysis of Maynard Smith's two-player, ESS model of biological signalling, the "Sir Philip Sidney game", is presented. The stable strategies of the players in this game are shown to satisfy the conditions of Zahavi's handicap principle. At equilibrium, signals are honest, costly, and costly in a way that is related to the true quality revealed. Further analysis reveals that the level of cost required to maintain stability is inversely related to the degree of relatedness between the players. It therefore seems likely that stable biological signalling systems will feature lower signalling costs when communication occurs between relatives. A three-player, extended version of the model is investigated, in which signals are passed via an intermediate, or "messenger". It is shown that this destabilizes the signalling system, and leads to increased signalling costs. This result suggests that "kin conflict" theories of the evolution of the endosperm in flowering plants require further refinement. The introduction of a novel resource acquisition tissue, which mediates parent-offspring interaction during development, cannot be assumed to limit parent-offspring conflict simply because it carries an extra copy of the maternally inherited genes. The ability to add such complications to the Sir Philip Sidney game and still obtain solutions makes it a very useful modelling tool. PMID- 1640724 TI - Cell cycle studies in acute myelogenous leukemia. AB - Since the proliferative characteristics of leukemia cells play an important role in determining response to therapy, one may assume that an alteration of these characteristics could be therapeutically beneficial. To this end appropriate methods should be used to evaluate the effects of bioactive agents on leukemia cells in vivo in patients. PMID- 1640725 TI - Minimal residual disease in interferon-treated chronic myelogenous leukemia: results and pitfalls of analysis based on polymerase chain reaction. AB - Therapy with interferon-alpha results in complete cytogenetic remission in 15-20% of patients with chronic myelogenous leukemia. Even during prolonged clinical follow-up, most of these patients do not relapse. However, because of the limited sensitivity of cytogenetic techniques (approximately 5%) and Southern blots (approximately 1%), it is uncertain whether the residual malignant clone becomes extinct or persists below the limit of detection in these patients. We used polymerase chain reaction to amplify the chimeric BCR-ABL transcripts in 18 patients with chronic myelogenous leukemia who became Ph1 chromosome negative while receiving treatment with interferon-alpha, either alone or in combination with interferon-gamma. At the time of study, these patients had been Ph1-negative for a median of 22+ months. Fifteen patients were positive for residual BCR-ABL transcripts. No residual BCR-ABL message was detected on analysis of multiple serial samples in three patients. In order to confirm these results, the samples from these three patients, along with positive and negative controls, were analyzed by two independent laboratories in a blinded fashion. In the first laboratory, RNA specimens from all three patients were considered negative using chemiluminescent acidinium-ester-labeled probes. In the second laboratory, samples from all three patients were also negative by conventional polymerase chain reaction (PCR). However, when a second round of amplification was carried out on the amplified samples using a different combination of primers, samples from two of the three patients were positive. The results confirm the presence of a small proportion of BCR-ABL-positive cells in the majority of patients who are in complete remission and highlight some of the potential problems of PCR-based analysis. There is a need to standardize PCR methodology and potential confounding factors need to be addressed before PCR can be generally applied to analysis of minimal residual disease in CML. The implications of BCR-ABL positivity for these patients are discussed. PMID- 1640726 TI - Childhood malignant non-Hodgkin lymphomas of uncommon histology. AB - Uncommon histologies were identified in 36 of 1336 cases (2.7%) of newly diagnosed childhood non-Hodgkin lymphoma (NHL). Seventeen cases were classified as follicular (six cases as mixed small and large cell, nine as large cell, and two as small non-cleaved cell) and 19 cases as diffuse (18 cases as mixed small and large cell, and one as small cell lymphocytic). The follicular pattern group included a preponderance of male patients; the median age at diagnosis was 11.7 years. These children presented primarily with low-stage disease involving lymph nodes or tonsils. All patients except one achieved complete remission and remain disease-free for 11 months to 18.8 years (actuarial 5-year event-free survival, 94%). The group with diffuse histologies was similar in sex ratio, age at diagnosis (median = 12.1 years), and nodal involvement, but tended to have more advanced-stage disease. Moreover, only 14 of 19 (74%) children with diffuse intermediate-grade histologies are alive in continuous complete remission (actuarial 5-year event-free survival, 70%). These results suggest that follicular pattern childhood NHL has an excellent prognosis, whereas cases with diffuse intermediate-grade histology are prognostically similar to those with diffuse high-grade histologies. PMID- 1640727 TI - Cytogenetic effects on cells derived from patients with myelodysplastic syndromes during treatment with hemopoietic growth factors. AB - Hemopoietic growth factors are used with increasing frequency in the treatment of patients with myelodysplastic syndromes (MDS). While a response occurs regularly, it has not been unequivocally resolved whether this effect is due to the stimulation of normal hemopoiesis or to induced maturation of the abnormal clone. To determine whether selective responses to colony-stimulating factors of normal versus abnormal clones occurred, cytogenetic analysis was performed on bone marrow cells of MDS patients before and during in vivo treatment with granulocyte macrophage colony-stimulating factor (GM-CSF) or recombinant human erythropoietin (rhEPO). A proliferation of additional clones could be demonstrated by karyotypic analysis in one patient during GM-CSF therapy and in two patients during rhEPO treatment. Two patients, initially with completely normal cytogenetics, developed a mixture of normal and abnormal metaphases during treatment. Two patients, initially with all abnormal metaphases, developed normal metaphases during treatment with GM-CSF. A mosaic of normal and abnormal metaphases was present in six patients. The percentage of abnormal metaphases increased in three patients during GM-CSF treatment, and in one patient during rhEPO therapy. The cytogenetic anomalies in one patient persisted after clinical response to treatment, suggesting that GM-CSF enhanced maturation of the abnormal clone. These data indicate that cytokine therapy in MDS may have diverse effects on hematopoiesis. PMID- 1640728 TI - Continuous-infusion daunorubicin and carboplatin for high-risk acute myeloid leukemia in the elderly. AB - Since continuous infusion of daunorubicin and of carboplatin have shown efficacy and reduced toxicity in early phase studies in acute myeloid leukemia (AML), 34 elderly patients with high-risk AML were treated with continuous infusion daunorubicin, 30 mg/m2 per day, from day 1 to day 4, and carboplatin, 200 mg/m2 per day from day 3 to day 7. Seven patients had therapy-related AML and/or AML following a myelodysplastic syndrome at diagnosis, 15 were in first and two in second relapse, and 10 were resistant to previous anthracycline and cytarabine therapy. Nine patients or 26%, with a 95% confidence interval (CI) ranging from 18-67%, achieved complete remission, including one patient at diagnosis (14%, CI: 0-58%), seven with relapsed AML (41%, CI: 18-67%), and one with resistant AML (10%, CI: 0-45%). Median durations of neutropenia below 0.5 x 10(9)/l and of thrombocytopenia below 20 x 10(9)/l were 24 and 20 days respectively. Severe toxicity included infections in 20 patients (59%), bleeding in two (6%), cardiac anomalies in two (6%), and vomiting in one (3%). Overall four patients (12%) died from chemotherapy related toxicity and 21 (62%) had resistant disease. Median overall survival was 4 months and median disease-free survival 8 months. We conclude that this regimen had efficacy with reduced toxicity in relapsed patients. Higher dosages for the same drugs could be tolerated by better risk patients for precise evaluation of cross reactivity with cytarabine-based regimens. PMID- 1640729 TI - Autologous bone marrow transplantation followed by interleukin-2 in children with advanced leukemia: a pilot study. AB - In an attempt to prolong disease-free survival in children with acute leukemia, we tested the feasibility of interleukin-2 (IL-2) administration after an autologous bone marrow transplantation (ABMT). We report the clinical and biological data obtained in three children with acute myelocytic leukemia (AML) in second complete remission (CR) and in seven children with acute lymphocytic leukemia (ALL) in second or subsequent CR, who received IL-2 at a median interval of 78 days (range 38-125) from ABMT. Patients were treated with 1-2 cycles of IL 2 given by continuous infusion over a 5-day period using a daily escalating protocol, from 100 micrograms/m2 per day to the maximum tolerated dose, followed after 3 weeks by low-dose IL-2 for 5 days monthly over a 6-h infusion on an out patient basis. Side effects greater than grade 2 (WHO system), consisting of thrombocytopenia, fever, cutaneous rash, nausea and vomiting, diarrhoea were common during the high-dose IL-2 cycles, but resolved 24-48 h after stopping IL 2. Only one patient developed liver toxicity (grade 3, WHO) on day +3 of the first cycle which prompted us to stop the administration of IL-2. An increase in lymphocytes and eosinophils was also observed. IL-2 treatment was followed by a normalization of NK function and by the generation of a high proportion of endogenous LAK cells. All seven ALL patients relapsed at a median of 5 months (range 1-23). Two AML patients relapsed at 1 and 11 months, while the other is still in continuous CR at 23 months after IL-2 treatment. Our IL-2 schedule for treatment of leukemia in children after ABMT is thus feasible but its efficacy requires further investigation. PMID- 1640730 TI - P190-type bcr/abl expressed in myeloid colonies in a patient with Ph1-positive acute lymphoblastic leukemia. AB - In Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL), some cytogenetic studies have suggested clonal derivation from a multipotential stem cell. The role of the product of the chimeric gene, P190, is not, however, well understood. We examined the expression of P190-type bcr/abl in single hematopoietic colonies obtained at various clinical stages of a patient with Ph1 positive ALL, using the polymerase chain reaction (PCR). Seven out of 58 colonies examined expressed P190-type bcr/abl. Five out of seven colonies were granulocyte/macrophage (GM) colonies and two were erythroid colonies. The cell lineages of these colonies were confirmed by testing for the expressions of the myeloperoxidase (MPO) gene in the GM colonies and the beta-globin gene in the erythroid colonies. These results suggest transformation of multipotential stem cell in this patient and confirm that expression of the P190-type bcr/abl fusion gene permits stem cell differentiation leading to Ph1-positive ALL. PMID- 1640731 TI - Impaired degradation of Ca(2+)-regulating second messengers in myeloid leukemia cells. Implications for the regulation of leukemia cell proliferation. AB - Inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate are Ca(2+) regulating second messenger molecules which are generated via the cleavage of inositol lipids. We have previously shown that these species are autonomously generated in HL60 myeloid leukemia cells and that they may play a role in signalling the continuous proliferation of this cell line. Here we show that the activity of the 5-phosphomonoesterase (5-PME) enzyme which cleaves and inactivates these second messengers was strikingly reduced in HL60 cells compared to normal granulocytes or macrophages. Induction of differentiation of HL60 cells along the monocyte/macrophage or granulocytic pathways did not result in a significant increase in 5-PME activity. The activity of this enzyme was also low in extracts of bone marrow mononuclear cells from four patients with myeloid leukemia. A lesion in the 5-PME pathway may therefore result in the conservation of Ca(2+)-regulating second messengers in the HL60 cell line and in some myeloid leukemia cells. It is plausible that this lesion may co-operate with the autonomous cleavage of inositol lipids in the signalling of leukemic cell proliferation. PMID- 1640732 TI - All-trans-retinoic acid induced enrichment of functionally normal neutrophils in vivo in a patient with acute promyelocytic leukemia. AB - A patient with resistant acute promyelocytic leukemia was treated with all-trans retinoic acid (45 mg/m2 per day for 42 days) and obtained complete remission at day 14. Analysis of the neutrophils from the patient at day 7 demonstrated that they were indistinguishable from neutrophils from normal individuals as far as this is assessed by presently available functional tests. Furthermore, the degree of peroxidase positivity of neutrophils obtained from the patient was similar to control values. Thus, taken together with the hematologic features, all-trans retinoic acid induces leukemic promyelocytes to become functionally normal neutrophils. This therapy is particularly suitable in obtaining complete remission in patients with acute promyelocytic leukemia with neutropenia with or without previous chemotherapy. PMID- 1640733 TI - Defective production of granulocyte-macrophage colony-stimulating factor and interleukin-1 by mononuclear cells from children treated for acute lymphoblastic leukemia. AB - The production of colony-stimulating activity (CSA) by phytohemagglutinin (PHA) stimulated peripheral blood mononuclear cells (PBMC) from patients receiving maintenance chemotherapy for acute lymphoblastic leukemia (ALL) was examined. Supernatants from only 14 of 22 patient PBMC cultures (64%), but all supernatants from normal PBMC cultures, supported myeloid colony growth. When present, colony stimulating activity always included granulocyte-macrophage colony-stimulating factor (GM-CSF). In addition, in nine of ten patient studies and in all control studies, stimulated PBMC produced interleukin-1 (IL-1). These results show that the chemotherapy administered to children with ALL can damage the cytokine production mechanisms in PBMC; the diminished ability to produce GM-CSF and IL-1 may contribute to the increased risk of overwhelming infection in these patients. PMID- 1640734 TI - Effect of combined treatment with interleukin-3 and interleukin-6 on 4 hydroperoxycyclophosphamide-mediated reduction of glutathione levels and cytotoxicity in normal and leukemic bone marrow progenitor cells. AB - 4-Hydroperoxycyclophosphamide (4-HC) is widely used as an ex vivo bone marrow purging agent for acute myeloid leukemia (AML) blasts. We have determined the effect of a combined treatment with interleukin 3 (IL-3) plus IL-6 on 4-HC cytotoxicity against normal (CFU-GEMM) versus AML (L-CFU) bone marrow progenitor cells. Following an 18 h exposure to IL-3 plus IL-6, treatment with 4-HC in conjunction with IL-3 and IL-6 for one hour resulted in a significantly greater inhibition of L-CFU versus CFU-GEMM colony growth. In addition, treatment with IL 3 plus IL-6 reduced the inhibitory effects of higher concentrations of 4-HC on CFU-GEMM but not L-CFU growth. IL-3 and IL-6 did not protect the self-renewing, clonogenic, AML blast progenitor cells from the cytotoxic effects of 4-HC. While the total intracellular glutathione (GSH) levels were not significantly different between untreated normal bone marrow mononuclear cells (NBMMC) and AML blasts, greater intracellular GSH-S transferase activity was observed in the NBMMC. 4-HC produced a marked reduction in GSH levels in NBMMC as well as AML blasts. But treatment with IL-3 plus IL-6 in conjunction with 4-HC resulted in significantly higher GSH levels in NBMMC. These differences in intracellular GSH levels and GST activity may offer an explanation for the differential protective effects of IL-3 plus IL-6 treatment against the cytotoxic effects of 4-HC on CFU-GEMM colony growth. PMID- 1640736 TI - Induction of differentiation in Friend-erythroleukemia cells by aclacinomycin A: early transient decrease in c-myc and c-myb mRNA levels. AB - Chemical inducers of the differentiation are known to cause an early transient decrease in c-myc and c-myb mRNA levels in Friend erythroleukemia cells preceding the down-regulation of c-myc and c-myb expression in the course of irreversible terminal differentiation. We therefore investigated the early effect of the potent differentiation-inducing anthracycline antitumor antibiotic, aclacinomycin A, on the c-myc and c-myb mRNA levels in the Friend cell line, F4-6, using Northern blot analysis. Aclacinomycin A induced a rapid decrease in the levels of c-myc and c-myb transcripts within 0.5-1 h and 2-3 h, respectively. The time course of decline in c-myc and c-myb expression was similar to that observed with dimethylsulfoxide or after transcription blockage brought about by a high concentration of actinomycin D. By 12 to 18 h after aclacinomycin A exposure, the c-myc and c-myb mRNA levels had returned to about pretreatment levels. When the cells were treated with adriamycin, an anthracycline that reduces cell proliferation in F4-6 cells without increasing differentiation, an early decrease in c-myc and c-myb expression was not observed. These results suggest that the transient decrease in c-myc and c-myb mRNA levels in F4-6 cells may be an early differentiation-related biochemical effect of aclacinomycin A. PMID- 1640735 TI - Accumulation of T-cell clones producing high levels of both granulocyte macrophage and macrophage colony-stimulating factors (CSF-1) in lymph nodes involved by Hodgkin's disease. AB - We have previously shown that total T cells derived from lymph nodes (LN) involved by Hodgkin's disease (HD) secrete higher levels of colony-stimulating activity than total T cells present within benign hyperplastic (BH) LN and B-non Hodgkin's lymphoma (B-NHL) LN, suggesting that T cells with particular properties accumulate in HD LN. To further characterize this T-cell population, we have quantified production of both granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) production in a total of 98 T-cell clones (TCC) derived from CD25+ activated T cells present in HD LN; TCC derived from CD25+ T cells obtained from B-NHL LN(101 TCC), BH LN(95 TCC), and peripheral blood (PBL; 38 TCC) of healthy donors were used as controls. HD LN were characterized by the presence of an elevated number (44%) of TCC producing particularly high titers of both GM-CSF and M-CSF, whereas only a minority of such TCC was found in control groups (10% in B-NHL, 16% in BH, 8% in PBL). These observations support the hypothesis of a selection of T-cell families with particular properties occurring in contact with Reed-Sternberg (RS) cells. According to the biological properties of GM-CSF and M-CSF, it seems reasonable to suggest the involvement of this particular subset of T cells in the granulomatous process, the peripheral blood polynucleosis, and in the paracrine growth of RS cells. PMID- 1640737 TI - Glucose metabolism of hairy cells. AB - Hairy cell leukemia is a malignant B-cell disorder characterized by splenomegaly and pancytopenia. The malignant cell is morphologically unique and characterized by fine cytoplasmic projections. Although studies of the cell have revealed important information about its proliferative capacity, cell surface, and membrane composition, less is known about the metabolic characteristics of the cell. We have previously investigated the oxidative metabolism of the hairy cell and have suggested that hairy cells might have a unique glucose metabolism compared to normal lymphocytes. This is indicated by a high rate of [6 14C]glucose oxidation in short-term culture consistent with an active Kreb's cycle and a high ratio of [6-14C]glucose oxidation to [1-14C] glucose oxidation. In this study, we evaluated an additional group of patients with hairy cell leukemia prior to or after treatment with the experimental drug 2' deoxycoformycin (dCF). We found that in seven of eight patients the leukemic cells had a pattern similar to that previously described and that all of these seven patients had a significant response to therapy. The cells of the eighth patient had minimal Kreb's cycle activity, and at the time of study the patient was resistant to therapy with dCF. The metabolic activity of hairy cells may distinguish them from other lymphoid populations and may be a marker for sensitivity to dCF. PMID- 1640738 TI - p53 in chronic myeloid leukemia cell lines. AB - Four human chronic myeloid leukemia (CML) cell lines, BV173, K562, KCL-22, and KYO-1, were studied for inactivation of human tumor suppressor gene p53. Southern blotting showed allele deletion in KCL-22 and cytogenetic studies showed a chromosome 17 deletion in KYO-1 but no gross structural abnormalities in the other two lines. Northern blotting showed increased amounts of normal size p53 mRNA in BV-173 and KYO-1, trace amounts in KCL-22, and none in K562. Direct sequencing of p53 cDNA revealed a missense point mutation in KYO-1 and a single base pair deletion consistent with a coding frame shift in KCL-22. Both abnormalities in these myeloid cell lines were located in the highly conserved region of p53. Studies with two monoclonal antibodies showed that the three cell lines with p53 mRNA had readily detectable p53 proteins. In KYO-1 and BV173 cells the p53 protein was located mainly in the nuclei but KCL-22 cells had weak staining in the cytoplasm. Our data support the assumption that inactivation of p53 tumor suppressor function in myeloid blast transformation of CML may result from point mutations or deletions that produce mutant proteins. PMID- 1640739 TI - Concomitant chronic lymphocytic leukemia (CLL) and acute myeloid leukemia. Complete remission of CLL achieved with high-dose cytosine arabinoside. AB - The concomitant presentation of acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) is rare with so far only eleven cases reported. In addition, the achievement of complete remission (CR) in CLL is exceptional and generally not assessed by immunophenotypical investigations. We report a case with a simultaneous occurrence of AML and CLL in which, in addition to the complete remission of AML, an eradication of the CLL clone was obtained following high-dose cytosine arabinoside. The immunophenotypic investigation of minimal residual disease showed that less than 1 x 10(-3) CD19+/CD5+ B-cells remained in bone marrow. PMID- 1640740 TI - Can intensive chemotherapy cure chronic myelogenous leukemia? PMID- 1640741 TI - Steady-state point-source stimulation of a nerve containing axons with an arbitrary distribution of diameters. AB - The paper extends a mathematical model for point-source electrical stimulation of a nerve. In the original model, it was assumed that all the axons in the nerve have the same diameter. In this paper the model is extended to represent a nerve with an arbitrary distribution of axon diameters. It is shown that the assumption of identical axons is justified for a typical human nerve if the 'representative' axon diameter is taken as the area-weighted average of the diameter distribution. PMID- 1640742 TI - Damage in peripheral nerve from continuous electrical stimulation: comparison of two stimulus waveforms. AB - The propensity for two types of charge-balanced stimulus waveforms to induce injury during eight hours of continuous electrical stimulation of the cat sciatic nerve was investigated. One waveform was a biphasic, controlled-current pulse pair, each phase 50 microseconds in duration, with no delay between the phases ('short pulse', selected to excite primarily large axons), whereas in the second type each phase was 100 microseconds in duration, with a 400 microsecond delay between the phases (selected to excite axons of a broader spectrum of diameters). The sciatic nerve was examined for early axonal degeneration (EAD) seven days after the session of continuous stimulation. With both waveforms, the threshold stimulus current for axonal injury was greater than the current required to excite all of the nerve's large axons. The correlation between simple stimulus parameters and the amount of EAD was poor, especially with the 'short pulse' waveform, probably due to variability between animals. When the stimulus was normalised with respect to the current required to fully recruit the large axons, a good association between damage and stimulus amplitude emerged. The damage threshold was higher for the 'short pulse' waveform. The implications for clinical protocols are discussed. PMID- 1640743 TI - Tetrapolar electrode system for measuring physiological events by impedance. PMID- 1640744 TI - Laboratory assessment of Laerdal mouth tube mask prototype resuscitation device. PMID- 1640745 TI - Method for the fixation of optrodes in near-infra-red spectrophotometry. PMID- 1640746 TI - Intravascular oxygen sensor with polyetherurethane membrane: in vitro performance. PMID- 1640748 TI - Wavelets--new method of evoked potential analysis. PMID- 1640747 TI - Vortex mixing catheter. PMID- 1640750 TI - Personal computer system for ECG ST-segment recognition based on neural networks. AB - A personal computer system for electrocardiogram (ECG) ST-segment recognition is developed based on neural networks. The system consists of a preprocessor, neural networks and a recogniser. The adaptive resonance theory (ART) is employed to implement the neural networks in the system, which self-organise in response to the input ECG. Competitive and co-operative interaction among neurons in the neural networks makes the system robust to noise. The preprocessor detects the R points and divides the ECG into cardiac cycles. Each cardiac cycle is fed into the neural networks. The neural networks then address the approximate locations of the J point and the onset of the T-wave (T(on)). The recogniser determines the respective ranges in which the J and T(on) points lie, based on the locations addressed. Within those ranges, the recogniser finds the exact locations of the J and T(on) points either by a change in the sign of the slope of the ECG, a zero slope or a significant change in the slope. The ST-segment is thus recognised as the portion of the ECG between the J and T(on) points. Finally, the appropriateness of the length of the ST-segment is evaluated by an evaluation rule. As the process goes on, the neural networks self-organise and learn the characteristics of the ECG patterns which vary with each patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640749 TI - Conservation and characterisation of spatial features in a new method of data compression for body surface potential maps. AB - Body surface potential maps consist of a huge amount of data represented as a series of three-dimensional maps, which are time consuming to process and expensive to store. In spite of the continuous interest in body surface potential maps, their use has not become common and they are of no practical use in the clinics. This is due to the overwhelming amount of measured data required to generate the maps and the lack of quantitative methods to analyse them. Data compression or reduction may solve these deficiencies. Such a procedure must conserve the fine spatial details of the maps, which are usually extracted from low level surface potentials, as these are reported to be significant in diagnostic electrocardiography. A technique is presented for data reduction, that implements two-level thresholding and conserves the fine significant spatial features of each map. A sequence of annuli thus produced is shown to describe the dynamic nature of the underlying process. This sequence is further processed and characterised by features which quantify its dynamic behaviour: time of annuli sequence appearance, its duration, three-dimensional loci of centres of mass of the annuli, distances between successive centres of mass and cross-correlation coefficients between successive annuli. To test the data reduction procedure and the usefulness of the features, maps from 20 subjects are studied (both normal patients and those with various pathologies). It is found that the use of annuli instead of the whole measured information allows simple storage, display and calculations; the features, which vary in time, represent closely the changes in location of the annuli and their dynamic variations of shape. The features are also found to be grouped together for the maps of the normal patients and for each pathology. Thus, body surface potential maps may become more commonly used in clinics by being represented by a set of features, which conserve their dynamic and spatial nature, and which may serve for classification of cardiac pathologies. PMID- 1640751 TI - Classification of pathologies by reduced sequential potential maps. AB - Body surface potential mapping (BSPM) is an electrocardiographic measuring technique which produces the data as a series of three-dimensional maps. These maps are assumed to contain information which may help classify subjects for diagnostic purposes more effectively than standard ECGs. As quantitative classification of the complete sequences of maps is complex and cumbersome, the present study uses extracted features which characterise the data. The features, which have been presented and evaluated in a recent work, have been extracted after the maps were processed by a compression technique which conserved the spatial details of the maps. The compression by two-level thresholding converted the sequences of maps into sequences of annuli, from which the following features were extracted: time indices, velocity vector magnitude, loci in three dimensional space of the centres of mass and cross-correlation coefficients between successive annuli in the sequence. Here, three different classification methods are applied to these features: statistical methods, the Fisher linear discriminant method and visual inspection. BSPMs from 54 subjects are used: 25 normal, 11 WPW syndrome and 18 CAD cases. It is found that by applying a decision role which comprises all features, the procedure offers a completely accurate classification of the subjects to their groups. The three-dimensional centre of mass is found to be the single best classifier; successfully categorising 20/25 of the normals 17/18 of the CAD patients and 11/11 of the WPW patients. PMID- 1640752 TI - Measurement of human BAERs by the maximum length sequence technique. AB - The traditional brainstem auditory evoked response (BAER) measurement technique (ensemble averaging) is time-consuming and is not acceptable for some time critical clinical applications. In the paper the application of a pseudorandom binary sequence, the maximum length sequence, to human BAER measurements is examined. This technique permits a faster click rate to stimulate the test subject, and obtains a higher signal-to-noise ratio (SNR) response through deconvolution. When compared with conventional averaging, the method can result in an improved SNR or in faster measurement of BAER. The theory of the technique and the experimental setup are presented, and theoretical analysis on the SNR improvement by this technique against averaging is also given. Actual measurements of BAER on both humans and cats indicate that this technique is effective, especially when the measurement time is not too long, or the number of trials is not too large. PMID- 1640753 TI - In vivo measurement of bone quality in the horse: estimates of precision for ultrasound velocity measurement and single photon absorptiometry. AB - The in vivo precision of ultrasound velocity measurement and single photon absorptiometry for the assessment of equine bone quality is discussed. In vivo precisions for ultrasound velocity measurements were less than 0.5 per cent, whereas cortical cross-sectional area, compact bone density and modulus of elasticity were around 1 per cent, and bone mineral content and density were just over 2 per cent. Except for ultrasound velocity, substantial improvements could be achieved by taking the mean of five readings for each measurement. The long term precision of the techniques was also high, with all precision values being less than 3 per cent. The possible sources of variation in ultrasound velocity measurements were also investigated. The method for combining ultrasonic and photon absorptiometric data for equine bone quality assessment has been proven to be highly accurate and precise. There appears to be no reason why the same principles cannot be applied with equal success to the noninvasive assessment of bone quality in humans. PMID- 1640754 TI - Effect of pulsatile arterial diameter variations on blood flow estimated by Doppler ultrasound. AB - High-resolution measurements of common carotid and femoral arterial diameters have been performed by ultrasound echo devices. When combined with pulsed Doppler measurements of cross-sectional averaged velocity in the same vessels, exact calculations of flow were made possible. The median peak-to-peak pulsatile diameter variations were 0.19 mm (2.8 per cent) in the femoral artery and 0.49 mm (6.7 per cent) in the common carotid artery. Flow values were calculated either by taking the time-averaged diameter as a constant value, or by taking into account the dynamic variations in diameter. In comparing the two values, a quantification of the magnitude of error introduced by the averaging of the diameter was made possible. An error in the range 1.5-3.8 per cent was found for the femoral artery, whereas the error in the common carotid artery was in the range 0.4-3.6 per cent despite the larger amplitude of the pulsations in this vessel. PMID- 1640755 TI - Dynamic control of breathing during exercise and hypercapnia. AB - The dynamic influences of end-tidal CO2 and exercise on ventilation are compared when CO2 and exercise are imposed separately and when they are imposed simultaneously. Five human subjects are studied. The subjects performed three trials: random work rate forcing, random CO2 inhalation and their simultaneous loading. The work rate was varied between 20 and 80 W as a pseudorandom binary sequence. The concentration of inspired CO2 was varied randomly between 0 and 7 per cent, adjusted so that it produced approximately the same amount of ventilatory fluctuations as the random work load. The relative contribution of each variable was analysed using multivariate autoregressive analysis at frequencies ranging from 0.1 to 1 cycle min-1. The results show that the dynamics of the response to CO2 inhalation, exercise and their combination are nonlinear and that the combination of CO2 inhalation and exercise magnifies the nonlinear behaviour. Ventilation is largely unaffected by either work rate or end-tidal CO2 at 1 cycle min-1. During simultaneous CO2 and work rate forcing, ventilation tends to follow the change in the end-tidal CO2. PMID- 1640756 TI - Portable system for acquisition and transmission of ECG parameters. AB - A simple inexpensive bedside automatic ECG data-collection system is presented. The main parameter measured is the R-R interval length that can be used in the construction of a heart rate variability signal. Another parameter measured is the shape of the T-wave in the ECG signal. The collected data are transferred to a remote host computer through the public telephone network, by means of a modem. The system can function through the whole range of human heart rates. The described solution differs from most existing ones by utilising the existing ECG monitoring equipment in hospitals, which usually does not store any information. This equipment is connected by a portable, independent, special-purpose system to a remote host computer which can further analyse and store the data. PMID- 1640757 TI - Effect of the metallic seal of a hermetic enclosure on the induction of power to an implant. AB - Most neuroprostheses which use integrated circuits protect these chip components in a hermetic package. No satisfactory method of sealing such an enclosure has been found which does not use metals. Therefore, in general, the seal is an electrically conducting ring. If induction is used to supply power to this device, this ring will be a 'short-circuited turn' which will affect the performance of the inductive link. In the paper, theory is presented for a model in which the metallic seal is a tertiary inductance, coupled to the primary and secondary. The tertiary has finite Q. Equations for this model are given from which formulae for the gain and efficiency are derived for the particular condition of tuning that the carrier frequency equals the resonant frequency of both the primary and secondary circuits. From the formulae, gain curves are plotted which show how the seal affects the link. However, it is clear that general solutions to the problem are needed if the theory is to be of practical use. PMID- 1640758 TI - Class E driver for transcutaneous power and data link for implanted electronic devices. AB - Magnetic transcutaneous coupling is frequently used for power and data transfer to implanted electronic devices. The paper describes a transmitter/coil driver based on the class E topology. The development of a 'high-Q approximation' simplifies the design procedure. A method of data modulation using synchronous frequency shifting is described. The class E circuit shows great promise, especially for circuits with unusually low coefficients of coupling. Transmitter coil currents of several amperes, at radio frequencies, with relatively low active device power dissipation, can easily be obtained. PMID- 1640759 TI - Mechanical and optical anisotropy of bovine pericardium. AB - A Moire fringe method was used to determine the shape of inflated disks of fresh bovine pericardium. The results suggested that the tissue was anisotropic and allowed the identification of the directions of the axes of elastic symmetry. Quantitative biaxial inflation and simple tension tests confirmed the anisotropy. In the circumferential direction the tissue was more extensible and had greater mean strength (18 MPa against 2.5 MPa) and mean terminal modulus (46 MPa against 14 MPa) than in the root-to-apex direction. The tissue was also optically anisotropic when viewed by transmitted polarised light and the directions of mechanical and optical anisotropy were related. PMID- 1640760 TI - Viscoelastic response of human hair cortex. AB - The present study describes a new methodological approach which allows the separate analysis and quantitative determination of the viscous and elastic components of human hair using a computerised experimental system. In a first series of experiments subsequent to the estimation of the cross-sectional surface area of the cuticle, the cortex and the medulla, the viscoelastic response of hair (considered as a homogeneous material) and of its cortex were determined in ten hair specimens derived from the same human subject. Statistically significant differences were found between hair and its cortex with regard to the values of the modulus of elasticity, limit of linearity and post-yield slope. In a second series of experiments the viscoelastic parameters of hair and its cortex were separately determined in 100 hair specimens derived from ten healthy human subjects (ten specimens from each subject). It was found that the dispersion of the values of modulus of elasticity, limit of linearity and post-yield slope of the cortex was significantly reduced compared with that of the hair. Our results indicate that the pattern of the viscoelastic parameters of human hair cortex, which strongly depends on its microstructural features, may be regarded as a more reliable and sensitive diagnostic marker than that of hair in various structural and functional hair disorders. PMID- 1640761 TI - Triaxial force transducer for investigating stresses at the stump/socket interface. AB - Although normal pressures at the stump socket interface of the lower-limb amputee have been investigated, little is known about the shear stresses that also occur. Studies suggest that the combination of both shear and normal stresses significantly exacerbates discomfort and vascular and tissue damage. A means of simultaneously measuring normal and shear stresses will aid in the investigation and improvement of prosthetic fit. A miniature triaxial force transducer (4.9 x 16 mm diameter) has been developed which can be recessed into the socket wall. The principle of operation, construction, performance and limitations of the device are described. Preliminary measurements of the interface stress variations over the gait cycle in a supra-condylar PTB socket are presented. These show clear differences in the stress patterns present when two different prosthetic feet are used. PMID- 1640762 TI - Time series analysis of brain potentials preceding voluntary movements. AB - Brain potentials preceding voluntary movements, obtained after averaging single trial EEG records synchronised with the start of movement, consist of slow potentials shifts SPS in the negative direction mixed with faster components like ongoing EEG activity. Two hypotheses were tested: SPS could be presented by a sum of smooth function (trends) and weakly stationary processes (residuals); the residuals and the ongoing EEG activity preceding SPS could be described by the same class of autoregressive (AR) or autoregressive moving average (ARMA) models. The trend was estimated by comparing several approximating functions in the sense of least mean square error. The SPS residuals, after subtracting the trend and background EEG activity, were estimated using AR and ARMA models of different orders. These procedures were performed on brain potentials recorded from vertex to linked ear lobes of five subjects instructed to voluntarily press a button. As a result, the hypotheses were not rejected. The trend was best approximated by a hyperbolic function or Chebyshev's second order polynomial. AR models fitted both the SPS residuals and ongoing EEG activity well enough. In conclusion, SPS were characterised by three parameters of the smooth function plus a time parameter defined by the potential boundaries. PMID- 1640763 TI - Skin impedance measurements using simple and compound electrodes. AB - We have studied the effect of the electrode configuration on the measurement of body impedance and found that the electrode configuration greatly affects the impedance measurement using the four-electrode method. We studied the characteristics of the compound electrode and found that the compound electrode provides the four-electrode method in a compact form. A new method of measuring the skin impedance using simple electrodes at low frequencies was developed. At high frequencies where the effect of internal tissue impedance is not negligible, we used the compensation method using compound electrodes, because they measure the voltage right under the skin. At 50 kHz, we measured the real part of the skin impedance of less than 80 omega on the thorax. We propose a simple instrument which can measure accurate skin impedance at various frequencies. PMID- 1640764 TI - The structure of the Mental Health Inventory among Chinese in Taiwan. AB - This study attempted to ascertain the construct validity and external validity of the Mental Health Inventory in a Chinese population in Taiwan and contrast these results with results obtained from studies of several U.S. populations. In particular, a series of measurement models were specified and evaluated to address the issues of reliability and validity. Data were collected from personal interviews of a probability sample of 1,194 Chinese respondents 14 years of age and older in four townships in southwest Taiwan. The Mental Health Inventory was found to involve two major components: positive well-being and psychological distress. As a hierarchical structure, each component consists of one second order and two or three first-order factors. The relationships between well-being and distress can be characterized as substantially independent and modestly bipolar depending on the level and specification. PMID- 1640766 TI - The feasibility of a public-private long-term care financing plan. AB - In this study, the feasibility of a public-private long-term care (LTC) financing plan that would combine private LTC insurance with special Medicaid eligibility requirements was assessed. The plan would also raise the Medicaid asset limit from the current $2,000 to the value of an individual's insurance benefits. After using benefits the individual could enroll in Medicaid. Thus, insurance would substitute for asset spend-down, protecting individuals against catastrophic costs. This financing plan was analyzed through a computer model that simulated lifetime LTC use for a middle-income age cohort beginning at 65 years of age. LTC payments from Medicaid, personal income and assets, Medicare, and insurance were projected by the model. Assuming that LTC use and costs would not grow beyond current projections, the proposed plan would provide asset protection for the cohort without increasing Medicaid expenditures. In contrast, private insurance alone, with no change in Medicaid eligibility, would offer only limited asset protection. The results must be qualified, however, because even a modest increase in LTC cost growth or use of care (beyond current projections) could result in substantially higher Medicaid expenditures. Also, private insurance might increase personal LTC expenditures because of the added cost of insuring. PMID- 1640765 TI - The trade-off between hospital cost and quality of care. An exploratory empirical analysis. AB - The debate concerning quality of care in hospitals, its "value" and affordability, is increasingly of concern to providers, consumers, and purchasers in the United States and elsewhere. We undertook an exploratory study to estimate the impact on hospital-wide costs if quality-of-care levels were varied. To do so, we obtained costs and service output data regarding 300 U.S. hospitals, representing approximately a 5% cross section of all hospitals operating in 1983; both inpatient and outpatient services were included. The quality-of-care measure used for the exploratory analysis was the ratio of actual deaths in the hospital for the year in question to the forecasted number of deaths for the hospital; the hospital mortality forecaster had earlier (and elsewhere) been built from analyses of 6 million discharge abstracts, and took into account each hospital's actual individual admissions, including key patient descriptors for each admission. Such adjusted death rates have increasingly been used as potential indicators of quality, with recent research lending support for the viability of that linkage. The authors then utilized the economic construct of allocative efficiency relying on "best practices" concepts and peer groupings, built using the "envelopment" philosophy of Data Envelopment Analysis and Pareto efficiency. These analytical techniques estimated the efficiently delivered costs required to meet prespecified levels of quality of care. The marginal additional cost per each death deferred in 1983 was estimated to be approximately $29,000 (in 1990 dollars) for the average efficient hospital. Also, over a feasible range, a 1% increase in the level of quality of care delivered was estimated to increase hospital cost by an average of 1.34%. This estimated elasticity of quality on cost also increased with the number of beds in the hospital. PMID- 1640767 TI - The protracted demise of medical technology. The case of intermittent positive pressure breathing. AB - In this study, the effects of hospital, staff, and patient characteristics on the rates of use and abandonment of an outmoded medical technology, intermittent positive pressure breathing (IPPB) are analyzed. The study focuses specifically on the use of IPPB to treat inpatients with chronic obstructive pulmonary disease in a national sample of more than 500 community hospitals from 1980 to 1987. Cross-sectionally, hospitals with shorter case-mix-adjusted lengths of stay, private nonprofit or investor-owned hospitals, and hospitals located outside of the north central United States were more likely to abandon IPPB by 1980. Teaching status, location, ownership, volume, and source of payment all appeared to affect rates of IPPB use in 1980. The longitudinal analysis examines both the probability a hospital abandoned IPPB and declines in rates of IPPB use over the study period, conditioned on the availability of IPPB in 1980. The results show that changes in the characteristics of hospitals, patients, and physicians all help to explain variations in the abandonment of IPPB. These findings contrast with previous studies of technological change, which find hospital size to be the most important variable. Size is important in explaining the rate of use in 1980, but it has no effect on the rate of decline in use or abandonment after 1980. In general, the analysis demonstrates that a combination of factors, economic incentives as well as information, contribute to the abandonment of outmoded medical technologies. Given the surprisingly long time periods required for this process to occur, the analysis underscores the need to strengthen financial incentives that encourage appropriate medical decisions and to disseminate information about the efficacy of specific procedures more widely and effectively. PMID- 1640768 TI - Duration and intensity of striking among participants in the Ontario, Canada doctors' strike. PMID- 1640769 TI - Correction and update on 'priority setting in medical technology assessment'. PMID- 1640770 TI - Coordinate-based mapping--a new method in health services research. AB - The Finnish national hospital discharge registers from 1985 and 1988 have been analysed by the National Board of Health. Results are provided for all the 21 Finnish hospital districts and central communal organizations. The small area variation phenomenon in hospital utilization cannot be explained by demographic or epidemiological factors. Rather, the variations seem to be largely due to organizational factors. The project aims to develop a data processing system capable of handling information on one million patients rapidly and economically, and show the results in an intelligible form as a table with standard headers or as a map illustration. Maps are superior to traditional statistical tables in demonstrating regional variations in health care utilization and in mortality. Maps based on small administrative units are useful for many purposes. These maps are, however, relatively 'noisy' due to substantial random variation. Coordinate based mapping is a method to overcome some of these difficulties. It is based on linking hospital discharge and mortality data with exact address data. The method allows mapping independent of administrative boundaries. Several examples of coordinate-based maps are given. The method is used in Finland for annual analysis of hospital use. PMID- 1640771 TI - Visual knowledge processing in computer-assisted radiology: a consultation system. AB - This paper presents Visual Heuristics, a consultation system for diagnosis based on thorax radiograph recording. Visual Heuristics uses both prototypical representations of physiological and pathological states and reasoning aimed to infer conclusions from pathological or physiological conditions, establishing correspondences between pathological or physiological states and semantic descriptions of images. Images are assembled with groups of descriptors that guide the recognition process, achieving the possibility of comparisons with real images on the basis of 'expected' images. The system may be employed to generate a dynamic atlas that does not contain proper images, but generates them. PMID- 1640772 TI - A cooperative approach to decision support in the differential diagnosis of breast disease. AB - The problem of differential diagnosis in breast histopathology is described and areas in need of decision support identified. It is argued that the conventional role played by decision support systems, i.e. that of the 'autonomous problem solver', is unacceptable in this domain and that support must be given to the actual cognitive functions of potential system users. Decision-making processes of pathologists are examined with particular reference to Rector's category of 'broad experts'. Pathologists possess a rich set of general diagnostic concepts for their domain, but their knowledge of detailed aspects of differential diagnosis may contain gaps and errors. A cooperative model of decision support, which utilizes the strengths and complements the weaknesses of pathologists' problem-solving skills, is described and the operation of this model within a functioning system illustrated. PMID- 1640773 TI - Decision support for patient management in oncology. AB - In this paper a novel approach to the development of the architecture of a knowledge-based decision support system for the management of patients with cancer of the breast is described. Its initial design and subsequent realization in a prototype version was facilitated by examining closely the overall clinical task and identifying its associated activities and related knowledge. Implementation in KEE highlights the value of rigorous conceptual modelling that leads to a design able to assess treatment response and disease progression as well as providing specific therapy advice. The approach is general and may be applied to the development of decision support systems for other areas of cancer and medicine. PMID- 1640774 TI - A pathology database system for autopsy diagnoses using free-text method. AB - Using natural language a computerized indexing and retrieval system was developed on a commercial database program, DATATRIEVE (Digital Equipment Corporation, Japan). Summarized anatomical diagnoses of nearly 4000 autopsy cases have been registered over a 13-year period at Tokyo Metropolitan Geriatric Hospital. There were 187,367 words in the pathological diagnoses with 4689 distinct words excluding articles, prepositions and conjunctions. 'Atrophy', 'congestion' and 'metastasis' were the most frequent words with frequencies of 4335, 3377, and 3373, respectively. Distinct clinical diagnoses were 2497, among which 'pneumonia', 'hypertension' and 'DIC' predominated. Each step of retrieval by character strings from the sequential data file requires less than a minute. PMID- 1640775 TI - Using the proportional hazards model to study heart valve replacement data. AB - The proportional hazards model is used to study the effect of various concomitant variables on the time to valve failure, mortality, or other complications, for patients who have had artificial heart valves inserted. The data are from a database, which is still being assembled as more information is acquired, at Killingbeck Hospital. A suite of computer programs, not specifically developed with this application in mind, has been used to carry out the exploratory data analysis, the estimation of parameters and the validation of the model. These three elements of the analysis are all illustrated. The present report is seen as a preliminary study to assess the usefulness of the proportional hazards model in this area. Follow-up work as more data are accumulated is intended. PMID- 1640776 TI - Information technology training for health care: information support. AB - The teaching of information technology (IT) within health care applications is currently diffuse. The diversity of specializations in health care presents special challenges in relation to IT training. An integrating training model which reflects the level of IT expertise needed is presented. PMID- 1640777 TI - Competency of human-derived Mycobacterium leprae to use palmitic acid in the synthesis of phenolic glycolipid-I and phthiocerol dimycocerosate and to release CO2 in axenic culture. AB - Insufficient numbers of viable Mycobacterium leprae have hampered metabolic studies using human-derived M. leprae. In this study, sufficient numbers of M. leprae were obtained from an untreated lepromatous patient to titrate the effects of pH on the metabolism of 14C-palmitic acid by M. leprae. Catabolic metabolism (oxidation of 14C-palmitic acid and release of 14CO2) was maximal when M. leprae were incubated at 33 degrees C and suspended in Middlebrook 7H9, ADC supplemented medium that had been buffered to maintain a pH of 4.8. Anabolic metabolism (synthesis of 14C-phenolic glycolipid-I and its precursor, 14C-phthiocerol dimycocerosate) was maximal when the pH was maintained at 6.8. PMID- 1640778 TI - Evaluation of Mycobacterium leprae particle agglutination test, using eluates of filter paper blood spots. AB - A comparison of the ELISA test with the newly-developed MLPA test was carried out, using eluates of blood spots from filter paper for the detection of the anti PGL-I antibody. A very good positive correlation was observed between these two tests. The concordance rate was found to be 92.6%, ranging from 71.4% to 100%. This nonconcordance was not found when freshly-collected samples were used. The MLPA test is simple and reliable. The use of eluates from blood spots collected on filter paper further simplifies the test in the collection and transportation of blood samples. This accurate and rapid method makes the MLPA test logistically feasible for large-scale screening. With our modification of MLPA with eluates more samples can be screened with the kit than with sera. PMID- 1640779 TI - Double-blind evaluation of BACTEC and Buddemeyer-type radiorespirometric assays for in vitro screening of antileprosy agents. AB - Two radiorespirometric assays, the BACTEC 460 and Buddemeyer-type 14CO2 detection systems, were evaluated in a double-blind manner for their ability to discriminate between authentic antileprosy agents and inactive compounds. Freshly harvested, nude-mouse derived Mycobacterium leprae were incubated in axenic media in the presence of coded test solutions prepared in a remote laboratory. Activity was assessed by comparing the rate of 14CO2 evolution from [1-14C]palmitic acid to controls. Breaking the code revealed that both systems demonstrated a dose response to ethionamide, pefloxacin and rifampicin as well as sensitivity to dapsone. Most of the water, ethanol, sucrose, dabsyl chloride and riboflavin negative-control samples failed to effect a significant reduction in radiorespirometric activity. This study confirms the ability of the radiorespirometric assays to function as a primary drug screening system in leprosy. PMID- 1640780 TI - Clinical observations on leprosy patients with HIV1-infection in Zambia. AB - The clinical observations carried out on 10 leprosy patients with HIV1-infection, admitted between 1.1.1986 and 1.5.1988 to the Salvation Army Hospital at Chikankata, Mazabuka, Zambia are described. A total of 8 of this group were newly diagnosed borderline leprosy patients. Their clinical data were compared with those of 34 newly-diagnosed borderline leprosy patients, admitted in the same period--50% were men, 50% women. The clinical presentation, with respect to leprosy, on admission, did not differ very much in both groups. The incidence of neuritis in both groups was 50% (respectively 5 and 17). The outcome of specific therapy of neuritis was worse in the HIV1 patients than in the other group: only partial recovery in 4 out of 5 and no response in 1, compared with a complete recovery in 10 cases, and a partial recovery in 7 cases in the other group. A total of 6 patients of the HIV1-group admitted to have had multiple heterosexual contacts, 5 had a history of sexually transmitted disease, 7 had generalized lymphadenopathy and 4 presented with another disease in addition to leprosy. While in hospital the group of 10 HIV1-infected patients suffered 17 episodes of intercurrent disease against none in the other group; 1 patient (male) died with generalized dermatitis and sepsis; 1 woman died with fulminant hepatitis. PMID- 1640781 TI - Diagnostic exploration of enlarged peripheral nerves in suspected cases of leprosy. An analysis of 55 cases. AB - In 55 cases presenting with enlarged peripheral nerves without any skin lesions, a rice grain-sized biopsy of the nerve lesion was taken for histopathological examination. As a result definitive diagnoses could be established: leprosy was diagnosed in 32 cases. In 23 cases the cause of nerve enlargement was not leprosy: post-traumatic neuritis 9, cysts 5, hypertrophic neuritis 3, nonspecific 4, neurofibroma 1, and amyloidosis 1. In all of these cases there was a deficit of the nerve function and postoperatively there were no complications. The authors, as a result of this experience, believe that surgical exploration and biopsy is a harmless diagnostic tool for establishing a definitive diagnosis of leprosy in cases presenting with enlarged peripheral nerves without any skin lesions. In 23 out of 55 such cases the nerve enlargement was proved to be other causes than leprosy. PMID- 1640782 TI - An application of the LePSA methodology for health education in leprosy. AB - This paper describes how the innovative LePSA technique can be used by community health workers to appropriately educate and increase compliance among leprosy patients. A lesson plan illustrating the interactive nature of the technique in a hypothetical Third World community is presented. The lesson plan, using MDT default, shows how the technique can elicit individual participation in a group setting and serve as both an educational and a behaviour change tool. PMID- 1640783 TI - Attitudes towards leprosy in the outpatient population of dermatology clinics in Trinidad. AB - We interviewed a total of 92 dermatology clinic patients using a brief questionnaire to determine their knowledge, attitudes and beliefs about leprosy. This small survey helped to confirm our suspicions that some knowledge of leprosy is lacking and that much stigma still remains. PMID- 1640784 TI - Attitudes of rural people in central Ethiopia towards leprosy and a brief comparison with observations on epilepsy. AB - To find out public attitudes toward leprosy a door-to-door survey was carried out in 1546 sampled households in the rural farming community of Meskan and Mareko in central Ethiopia, where the prevalence of leprosy is estimated to be 1:1000. Attitudes toward leprosy were compared with attitudes to epilepsy, studied in a previously performed survey in the same community. Eighty-seven per cent of the respondents were above the age of 25, and 59.5% were females. There were slightly more Muslims (54%) than Christians. The majority of the interviewees (87%) were farmers, with an illiteracy rate of 84%. Ninety-five per cent and 83%, respectively, were not willing to employ or work with a person having the disease. Seventy-five per cent would not allow their children to associate with a playmate suffering from leprosy. Comparative analysis of attitudes in the same community showed that negative attitudes toward leprosy were stronger than those toward epilepsy, particularly with regard to matrimonial associations, sharing of accommodation, and physical contact with an affected person. The reasons for these differences appear to be the community's deeply entrenched belief that leprosy is both hereditary and contagious, expressed respectively by 48% and 53% of the respondents. In order to minimize the perpetuation of negative attitudes, there is a need to educate and impress on the population that leprosy is a treatable infectious disease which is not congenitally acquired, and that it is even curable if detected early. The study reinforces previously proposed suggestions that, in developing countries such as Ethiopia, leprosy care should be integrated into the general health services. PMID- 1640785 TI - Appraisal of the knowledge and attitude of Nigerian nurses toward leprosy. AB - The attitudes of nurses toward leprosy are studied and in this paper. The findings show that their knowledge of leprosy is lacking and that they also fear leprosy. This study recommends that leprosy should be included in the basic nursing curriculum in order to increase awareness and to decrease the stigma of leprosy. PMID- 1640786 TI - Relationship problems between doctors and paramedical professionals working in leprosy with reference to a possible solution. AB - An empirical investigation was conducted on the in-group dynamics of health personnel working in leprosy. The sample populations were taken from the National Leprosy Eradication Programme (NLEP) employees of two state governments in India. They consisted of 21 doctors and 335 paramedicals, the former constituting a formal group and the latter a semiformal group. Two separate scales were developed for each of these groups to elicit information on five potential areas of intergroup relationships. The results indicated that there was very poor acceptance of the out-group and its roles, i.e. poor acceptance of the paramedicals by the doctors and vice versa. Three reasons were elicited from this study. First, doctors held their professional standing to be on a higher level than the paramedicals, leading to excessive social distancing between doctors and paramedicals. Second, multiprofessional involvement in NLEP work has increased the trend of professional overlapping, leading to a significant apprehension of the encroachment of skills. Third, there was a mutual lack of trust of each others professional skills. Despite these problems the otherwise more severe human relationship problems, such as domineering behaviour and prejudiced perception against the out-group were found to be significantly less in this study. In order to improve working relationships between these groups a method that has been used at Karigiri is recommended. The method has two parts. The first is aimed at intrapersonal understanding and the second at the development of interpersonal skills. Role play that mimics their original work situation and an analysis of case histories were the methods of teaching that were found to be more advantageous in internalizing these skills. PMID- 1640787 TI - A suggested new method to measure patch area in paucibacillary leprosy. PMID- 1640788 TI - Comment: Reversal reactions in leprosy and their management. PMID- 1640789 TI - Treatment of smear negative MB patients who had received previous dapsone monotherapy. PMID- 1640790 TI - '3 ps' in school surveys--'priming', privacy and a personalized approach. PMID- 1640791 TI - Second conference on AIDS in Asia and the Pacific. PMID- 1640792 TI - The serodiagnosis of leprosy. PMID- 1640793 TI - Endothelin and sarafotoxin: influence on steroid-regulated motility of rat uterus. AB - The sarafotoxins (SRTX) and endothelins (ET) were shown to influence the motility of the isolated rat uterus by inducing an increase in the rate and in the maximum tension of the spontaneous rhythmic contractions and a suppression of the relaxation phase of these contractions. Ovariectomized rats, 24 weeks post operation, show no spontaneous motility of their uteri and the SRTX/ET peptides induce only a slight tonic increase in the uterine tension. Treatment with 17 beta estradiol restores spontaneous motility and sensitivity to the SRTX/ET peptides in all three contraction modes. It is concluded that the influence of the SRTXs and ETs on uterine motility depends on the hormonal status of the animal. PMID- 1640794 TI - Receptor regulation, competitive antagonism and pA2. AB - A growing body of evidence suggests that the number of drug receptors on cell surfaces is not fixed, but is dynamically regulated by circumstances that include exposure to the ligand itself. Because most traditional theories of drug action are based on the assumption of a fixed number of receptors, it is desirable to examine the importance of this regulatory process on the interpretation of dose effect data. Of special interest is the impact of a variable receptor number on the equation of competitive antagonism and associated pA2 which, in the traditional theory, is a quantitative measure of antagonist-receptor affinity. Using a simple model of drug-induced endocytosis or exocytosis, it is shown that if the rate of either is appreciable, the pA2 is no longer a simple measure of affinity. PMID- 1640795 TI - Low doses of urethane effectively inhibit spinal seizures evoked by sudden cooling of toad isolated spinal cord. AB - The effect of low doses of urethane on three phases of spinal seizures evoked by sudden cooling (SSSC) of toad isolated spinal cord was studied. In control toads, SSSC began with a latency of 91 +/- 3 sec (mean +/- S.E.M.) exhibiting brief tremors, followed by clonic muscle contractions and finally reaching a tonic contraction (tonic phase). The latency of onset of seizures was significantly enhanced. The tonic phase was markedly abolished in toads pretreated intralymphatically with 0.15 g/kg of urethane. Tremors were the only phase observed in 55% of toads that received doses of 0.2 g/kg, and a total blockade of seizures was seen after doses of 0.25 g/kg of urethane in 50% of the preparations. A possible depressant effect of urethane on transmission mediated by excitatory amino acids is suggested. PMID- 1640796 TI - Blood-brain barrier dysfunctions following systemic injection of kainic acid in the rat. AB - Changes in blood-brain barrier (BBB) permeability and cerebral metabolic activity following intravenous injection of kainic acid (KA; 6, 12 mg/Kg) in rats were assessed by calculating respectively a blood-to-brain transfer constant (Ki) for [14C]alpha-aminoisobutyric acid and local cerebral glucose utilization (LCGU) values, at different times (1 h, or acute seizures phase, and 48 h, or chronic pathology phase) after the induction of seizures. A significant increase in the local permeability of the BBB was observed 1 h after the injection of KA 6 mg/Kg (eliciting no significant changes in cerebral metabolic activity, except within the frontal cortex and the hippocampus) and 12 mg/Kg (which induced a marked and widespread enhancement of LCGU). On the contrary, during the pathology phase, persistent regional increases in Ki values were evidenced in rats treated with the lowest dose of the convulsant, but not in rats injected with KA 12 mg/Kg (a dose able to cause extensive neuronal damage). Thus one can speculate that: 1) KA induced regional changes in the permeability of the BBB are not correlated with changes in neuronal activity; 2) opening of the BBB is not reliably associated with neuronal injury. PMID- 1640797 TI - Effects of atropine on operant test battery performance in rhesus monkeys. AB - The acute behavioral effects of atropine sulfate were assessed using a battery of complex food-reinforced operant tasks that included: temporal response differentiation (TRD, n = 7); delayed matching-to-sample (DMTS, n = 6), progressive ratio (PR, n = 8), incremental repeated acquisition (IRA, n = 8), and conditioned position responding (CPR, n = 8). Performance in these tasks is thought to depend primarily upon specific brain functions such as time perception, short-term memory and attention, motivation, learning, and color and position discrimination, respectively. Atropine sulfate (0.01-0.56 mg/kg iv), given 15-min pretesting, produced significant dose-dependent decreases in the number of reinforcers obtained in all tasks. Response rates decreased significantly at greater than or equal to 0.03 mg/kg for the learning and discrimination tasks, at greater than or equal to 0.10 mg/kg for the motivation and short-term memory and attention tasks, and at greater than or equal to 0.30 mg/kg for the time perception task. Response accuracies were significantly decreased at doses greater than or equal to 0.10 mg/kg for the learning, discrimination, and short-term memory and attention tasks, and at greater than or equal to 0.30 mg/kg for the time perception task. Thus, the order of task sensitivity to any disruption by atropine is learning = color and position discrimination greater than time perception = short-term memory and attention = motivation (IRA = CPR greater than TRD = DMTS = PR). Thus in monkeys, the rates of responding in operant tasks designed to model learning and color and position discrimination were the most sensitive measures to atropine's behavioral effects. Accuracy in these same task was also disrupted but at higher doses. These data support the hypothesis that cholinergic systems play a greater role in the speed (but not accuracy) of performance of our learning and discrimination tasks compared to all other tasks. Accuracy of responding in these and the short-term memory task, all of which involve the use of lights as visual stimuli, was more sensitive to disruption by atropine than those tasks which did not utilize such strong visual stimuli. PMID- 1640798 TI - Endothelin-3 modification of dopamine release in anaesthetised rat striatum; an in vivo microdialysis study. AB - Endothelin-3 (ET-3), a member of the vasoconstrictive peptide family, has recently been recognized as a neuropeptide. We used brain microdialysis and on line HPLC to examine the effect of ET-3 on the basal outflow of monoamines and their metabolites in the ketamine-anaesthetised rat striatum in vivo. Although intrastriatal infusion of ET-3 (40 pmol/rat) did not change basal dopamine (DA) release, after perfusion of DA releasing agent (5 x 10(-5) M ouabain or 120 mM KCl), ET-3 could increase the DA level. Further, these effects of ET-3 were attenuated by calcium-free Ringer. These data indicated that ET-3 may act by modifying the exocytosis from the striatum of rat brain to enhance DA release after depolarization induced by an agent such as KCl or ouabain. PMID- 1640799 TI - Effects of chronic morphine on biliary tract responses to cholecystokinin octapeptide in male guinea pigs. AB - Opioid peptides share the spasmogenic action of acutely administered morphine on the sphincter of Oddi. In this study, gallbladder function was assessed following chronic opioid administration. Implantation of morphine pellets (400 mg) in male guinea pigs depressed cholecystokinin-octapeptide(CCK)-induced emptying of gallbladder bile (monitored via a duodenal cannula). Gallbladder muscle strips, isolated from the morphine treated animals, showed depressed contractile responses to CCK. This antagonism was non-specific and indirectly mediated, as ACh contractions were also depressed, whereas CCK-induced contractions of gallbladder strips from untreated animals were unaffected by direct exposure to morphine (3 x 10(-6)M). The depression of CCK stimulation of bile flow by chronic morphine administration in male guinea pigs suggests that chronic exposure to opioids can impede gallbladder emptying. PMID- 1640800 TI - Chromogranin A correlates with norepinephrine release rate. AB - Chromogranin A (CgA) is an acidic protein co-released with catecholamines during exocytosis from sympathetic nerve terminals and chromaffin cells. Previous work has demonstrated that large scale perturbations in sympathetic nervous system (SNS) functioning result in corresponding changes in CgA levels in plasma. Little is known about the physiologic significance of CgA. We hypothesized that, since CgA and catecholamines are co-released from the same storage vesicles, and since CgA is not subject to reuptake or enzymatic metabolism, plasma CgA should reflect norepinephrine release from sympathetic terminals. We therefore measured venous CgA, norepinephrine levels, and norepinephrine release rate in 30 unmedicated subjects. Although the correlation of CgA with plasma norepinephrine was only modest (r = 0.37, p less than 0.05), its correlation with norepinephrine release rate was highly significant (r = 0.58, p less than 0.001). Thus, CgA may offer a novel perspective on peripheral sympathetic activity. PMID- 1640801 TI - Decreased glucose transporter 1 gene expression and glucose uptake in fetal brain exposed to ethanol. AB - Using pregnant rats fed equicaloric liquid diets (AF, and libitum-fed controls; PF, pair-fed controls; EF, ethanol-fed), we have previously shown that maternal alcoholism produces a specific and significant decrease of glucose in the fetal brain, which is accompanied by growth retardation. To further define the mechanisms of ethanol-induced perturbations in fetal fuel supply, we have examined (i) the uptake of 2-deoxyglucose (2-DG) by dissociated brain cells from fetal rats that were exposed to ethanol in utero and (ii) the steady-state levels of the glucose transporter-1 (GT-1) mRNA. A 9% decrease in brain weight (P less than 0.001) and a 54.8% reduction in 2-DG uptake into brain cells (P less than 0.02) were found in offspring of EF mothers compared to the AF group. Brain weight correlated with the rate of 2-DG uptake (P less than 0.05). Northern blot analysis showed a 50% reduction of GT-1 mRNA in EF brain relative to that in the AF and PF groups. We conclude that glucose transport into the brain is an important parameter altered by maternal ethanol ingestion. PMID- 1640802 TI - Protamine induces autophosphorylation of protein kinase C: stimulation of protein kinase C-mediated protamine phosphorylation by histone. AB - Protein kinase C (PKC), a protein phosphorylating enzyme, is characterized by its need for an acidic phospholipid and for activators such as Ca2+ and diacylglycerol. The substrate commonly used in experiments with PKC is a basic protein, histone III-S, which needs the activators mentioned. However, protamine, a natural basic substrate for PKC, does not require the presence of cofactor/activator. We report here that protamine can induce the autophosphorylation of PKC in the absence of any PKC-cofactor or activator; this may represent a possible mechanism of cofactor-independent phosphorylation of this protein. It was investigated if protamine itself can act as a PKC-activator and stimulate histone phosphorylation in the manner of Ca2+ and phospholipids. Experiments however showed that protamine is not a general effector of PKC. On the contrary, histone stimulated PKC-mediated protamine phosphorylation and protamine-induced PKC-autophosphorylation. Histone alone did not induce PKC autophosphorylation. Kinetic studies suggest that histone increases the maximal velocity (Vmax) of protamine kinase activity of PKC without affecting the affinity (Km). Other polycationic proteins such as polyarginine serine and polyarginine tyrosine were not found to influence PKC-mediated protamine phosphorylation, indicating that the observed effects are specific to histone, and are not general for all polycationic proteins. These results suggest that histone can modulate the protamine kinase activity of PKC by stimulating protamine-induced PKC-autophosphorylation. PMID- 1640803 TI - Anomalous binding of [3H]N-methyl-quinuclidinyl benzilate methyl chloride to human lymphocyte muscarinic receptors. AB - Using the muscarinic cholinergic ligand [3H]N-methyl quinuclidinyl benzilate methyl chloride ([3H]NM-QNB), we demonstrated that intact, viable human lymphocytes possess specific muscarinic binding sites. Equilibrium binding studies show that muscarinic acetylcholine receptor are divided into two subtype; high affinity (Ms) and low affinity types (Mw) for the ligand. PMID- 1640804 TI - Excitotoxin induction of ornithine decarboxylase in cerebral cortex is reduced by phospholipase A2 inhibition. AB - The enzyme ornithine decarboxylase (ODC) has been shown to be induced by a number of conditions such as cold-injury, kindling, ischaemia and excitotoxin injection. In previous studies we have characterised the cortical response to kainate injection into the nucleus basalis and shown a substantial increase in both ODC mRNA and enzyme activity which reaches a maximum at 8h. This response is completely prevented by treatment with MK-801, indicating the involvement of NMDA receptors in mediating this response. Whilst NMDA receptors are known to gate a cation channel leading to increased calcium entry, an additional effect on the release of arachidonic acid has been reported. The possibility that NMDA receptor mediated activation of phospholipase A2 and release of arachidonic acid might mediate this ODC response was investigated in this study by treatment with the phospholipase inhibitors quinacrine and dexamethasone. Treatment of animals with quinacrine (100 mg/kg) at the time of injection of kainate into the nucleus basalis caused a significant attenuation of the induction of ODC in cerebral cortex of 43%. No further attenuation was seen at higher doses. A similar reduction in ODC induction was seen after treatment with dexamethasone (1 mg/kg) but a greater effect could be obtained (65% attenuation) at higher doses. The possible involvement of arachidonic acid derivatives in mediating ODC induction was further investigated by treatment with the cyclo-oxygenase inhibitor indomethacin and the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA). Indomethacin was able to significantly attenuate the induction of ODC (greater than 60%) whilst NDGA (30 mg/kg) was ineffective. These results indicate the possible role of arachidonic acid derivatives in the regulation of the expression of ODC in cerebral cortex after excitotoxin injection. PMID- 1640805 TI - Fura-2 handling in a polarized epithelial barrier: the toad urinary bladder. AB - Toad bladders sacs were placed inside quartz cuvettes. When fura-2 AM was added to the mucosal compartment, low temperature (4 degrees C) almost completely blocked the transepithelial transfer of fluorescence observed at 20 degrees C (20 degrees C = 371 +/- 56, 4 degrees C = 29 +/- 29 fluorescence intensity in arbitrary units (FIAU), excitation at 340 nm, emission at 510 nm). Simultaneously, fluorescence accumulation inside the tissue was significantly higher (20 degrees C = 25 +/- 5, 4 degrees C = 91 +/- 24% increase on basal levels (%IBL)). When fura-2 AM was added to the serosal side, low temperature also reduced the serosal to mucosal transfer (20 degrees C = 149 +/- 36, 4 degrees C = 61 +/- 35 FIAU). Nevertheless, in this situation tissue accumulation, that was significantly higher that the one observed when fura-2 AM was added to the mucosal side, was reduced at low temperature (20 degrees C = 300 +/- 30, 4 degrees C = 48 +/- 7 %IBL). Spectral analysis of the mucosal and serosal compartments indicated that free fura-2 was transferred from the intracellular to the serosal compartment, but not to the mucosal one. These results indicate that fura-2 appears as a useful tool to evaluate the cellular distribution and traffic of polycyclic charged and non-charged molecules. PMID- 1640806 TI - Ethanol/cocaine interaction: cocaine and cocaethylene plasma concentrations and their relationship to subjective and cardiovascular effects. AB - To investigate the pharmacologic effects of the interaction between ethanol and cocaine, eleven male, paid volunteers familiar with the use of both ethanol and cocaine were tested in a dose-response, placebo-controlled, single-blind, randomly-assigned, cross-over design. Ethanol (0.85 g/kg) or placebo was administered in divided doses over a thirty minute period. Fifteen minutes after the termination of ethanol ingestion, cocaine HCl (1.25 and 1.9 mg/kg) or placebo (lidocaine and mannitol) was given by nasal insufflation (snorting). Cocaine and cocaethylene plasma concentrations, blood ethanol levels, subjective ratings of drug effects, and cardiovascular parameters were measured. Statistical analysis of the results indicate that: 1) cocaine administration did not alter blood ethanol concentrations nor the ratings of ethanol intoxication; 2) ethanol caused a significant increase in cocaine plasma concentrations, ratings of cocaine "high", and heart rate; 3) acute tolerance to the subjective and heart rate effects of cocaine was observed; 4) when combined with cocaine, ethanol led to the slow formation of cocaethylene in amounts much lower than those of its parent compound; and 5) the appearance of cocaethylene in plasma did not alter cocaine's subjective and cardiovascular effects. PMID- 1640807 TI - Effects of exercise on immune functions of undernourished mice. AB - Regular moderate exercise may modulate the response to a stressor and thus improve immune functions in conditions commonly associated with immunodepression and elevated levels of stress hormones. For example, anorexia nervosa patients, many of whom engage in regular aerobic exercise, generally have normal immune function and viral disease resistance in spite of their severe undernutrition. To test the hypothesis that exercise can prevent undernutrition-induced immunodepression, mice were fed a nutritionally complete, semi-purified diet, either ad libitum or in restricted quantities to induce 25% loss of initial weight over 3 weeks. Half the animals from each dietary group were run on a treadmill for 30 min/day, 5 days/week. Exercise had no effect on several measures of nutritional status. Spleen weight and blastogenic response to lipopolysaccharide were significantly increased by exercise in undernourished mice. In vivo antibody response to sheep red blood cells, and in vitro splenic responses to concanavalin A and phytohemagglutin were not significantly affected by exercise. Serum corticosterone level was increased by food restriction and significantly decreased by exercise in the undernourished mice. Within a treatment group there were no significant correlations between serum corticosterone level and any immune system measure. Hypothalamic concentration of uric acid was increased in food restriction groups and concentration of norepinephrine was increased in exercise groups. The results suggest that regular exercise may help prevent undernutrition-induced immunodepression, possibly through modulation of the stress response. PMID- 1640808 TI - In vitro oxidation of oxicam NSAIDS by a human liver cytochrome P450. AB - The nature of the enzyme(s) catalyzing the major metabolic pathway (5' hydroxylation) of oxicam NSAIDs was investigated in subcellular preparations of human liver tissue. Microsomal, but not cytosolic, fractions catalyzed the 5' hydroxylation of tenoxicam. This reaction required NADPH and was inhibited by various nonselective P450 inhibitors (CO, SKF-525A, ketoconazole), but not by the peroxidase inhibitor NaN3. Tenoxicam 5'-hydroxylation exhibited simple Michaelis menten kinetics compatible with catalysis by a single enzyme, but it strongly inhibited its own oxidation at concentrations higher than 100-150 microM. Piroxicam competitively inhibited tenoxicam 5'-hydroxylation and, conversely, tenoxicam competitively inhibited piroxicam 5'-hydroxylation. Tenoxicam 5' hydroxylation kinetics were similar in microsomes from one poor and five extensive metabolizers of debrisoquin (CYP2D6). Dextromethorphan (CYP2D6 prototype substrate) and midazolam (CYP3A prototype substrate) had no influence on tenoxicam 5'-hydroxylation, whereas mephenytoin, tolbutamide and sulfaphenazole (Ki = 0.1 microM) inhibited it. This indicates that the 5' hydroxylation of both piroxicam and tenoxicam is predominantly catalyzed by at least one cytochrome P450 isozyme of the CYP2C subfamily. PMID- 1640809 TI - DAU 6285: a novel antagonist at the putative 5-HT4 receptor. AB - The antagonistic properties of DAU 6285, an azabicycloalkyl benzimidazolone derivative, at putative 5-hydroxytryptamine4 (5-HT4) receptors were investigated in in vitro preparations of guinea-pig ileum and human atrium, in comparison to ICS 205-930. DAU 6285 behaved as a competitive antagonist in all the preparations examined. Its affinity (pA2) ranged between 6.50 and 7.12 in the test models considered. The affinity of ICS 205-930 was 2-3 fold lower. At variance with ICS 205-930, DAU 6285 displayed a weak affinity for 5-HT3 receptors (pKi = 6.1, rat cortex; pA2 less than 5, guinea-pig ileum). In the guinea-pig ileum, DAU 6285 (10 microM) did not exert antimuscarinic, antihistaminic, antinicotinic or myolytic activity. Moreover, it did not bind to other 5-HT receptor subtypes, or to adrenergic, dopaminergic, benzodiazepine, nicotine, GABA receptors. DAU 6285 may represent a suitable tool for studies in the field of 5-HT4 receptors. PMID- 1640810 TI - In vivo binding of [11C]tetrabenazine to vesicular monoamine transporters in mouse brain. AB - The time course of regional mouse brain distribution of radioactivity after i.v. injection of a tracer dose of [11C]tetrabenazine ([11C]TBZ) has been determined. Radiotracer uptake into brain is rapid, with 3.2% injected dose in the brain at 2 min. Egress from the brain is also very rapid, with only 0.21% of the injected dose still present in brain at 60 min. Radiotracer washout is slowest from the striatum and hypothalamus, consistent with binding to the higher numbers of vesicular monamine transporters in those brain regions. The rank order of radioligand binding at 10 min after injection is striatum greater than hypothalamus greater than hippocampus greater than cortex = cerebellum, similar to that found using in vitro assays of the vesicular monoamine transporters. Maximum ratios of striatum/cerebellum and hypothalamus/cerebellum were 2.85 +/- 0.52 and 1.69 +/- 0.25, respectively, at 10 min after injection. Co-injection of unlabeled tetrabenazine (10 mg/kg) or pretreatment with reserpine (1 mg/kg i.p., 24 h prior) was used to demonstrate specific binding of radioligand in striatum, hypothalamus, cortex, hippocampus and cerebellum. Distribution of [11C]TBZ was unaffected by pretreatment with the neuronal dopamine uptake inhibitor GBR 12935 (20 mg/kg i.p., 30 min prior). [11C]Tetrabenazine is thus a promising new radioligand for the in vivo study of monoaminergic neurons using Positron Emission Tomography. PMID- 1640811 TI - Effects of cyclosporin A on induced HIT cell alkalinization. AB - We studied whether therapeutic doses of cyclosporin A (CsA) modify the effects of nutrient and non-nutrient stimuli on pHi, in the insulin-secreting beta-cell line HIT-T15. Glucose caused a transient acidification, followed by alkalinization. CsA failed to block this alkalinization. PMA elicited a gradual alkalinization by a protein kinase C mediated mechanism which is not inhibited by CsA. The depolarization with high K+ was associated with a rise in pHi. CsA was able to completely block this increase in pHi. Ionomycin induced a rapid cytosolic alkalinization partially inhibited by CsA. We conclude that in HIT-T15 cells, therapeutical doses of CsA inhibit the Ca(2+)-dependent pathway of Na+/H+ antiport activation but not protein kinase C activation of this exchanger. PMID- 1640812 TI - Effects of endothelin on microcirculation of the pancreas. AB - Endothelin, a newly described endothelial-derived peptide, has potent vasoconstrictive properties and has been speculated to play a physiological role in the regulation of blood flow in some organs. The present study was designed to evaluate the effects of endothelin-1, endothelin-2 and endothelin-3 on the pancreatic microcirculation. Pancreatic tissue blood flow was measured by a laser Doppler flow meter in anesthetized dogs and endothelin-1, endothelin-2 or endothelin-3 was injected intravenously in graduated doses. Endothelins induced dose-dependent decreases in pancreatic tissue blood flow. Endothelin-1, endothelin-2 and endothelin-3 at a dose of 100 pmol/kg reduced pancreatic blood flow by 45.4%, 19.6% and 51.9%, respectively, whereas systemic arterial blood pressure was not significantly affected. When endothelin-3 was administered at a dose of 1000 pmol/kg, pancreatic blood flow was decreased by 73.5% with a concomitant increase of systemic arterial blood pressure by 17.6%. Endothelins potently decreased pancreatic tissue blood flow, suggesting a possible role of these agents in regulating the pancreatic microcirculation. PMID- 1640813 TI - The use of microdialysis for studying the regional effects of pharmacological manipulation on extracellular levels of amino acids--some methodological aspects. AB - The purpose of this study was to examine and validate the use of microdialysis for sampling and pharmacologically manipulating extracellular amino acids in the brain. Repeated use of microdialysis probes in acute intracerebral experiments did not significantly alter the relative recovery in vitro for the amino acids quantitated (GABA, aspartate, glutamate, glycine, taurine, and alanine). Regional differences in basal levels of some of the amino acids were detected in dialysates collected from the dorsomedial hypothalamus, striatum, and frontal cortex. The percent in vitro recoveries for the amino acids from the probes used in the three regions were not significantly different suggesting that the regional differences in basal levels of amino acids were functionally derived and not a consequence of variations in probe recovery. Perfusion with nipecotic acid, an inhibitor of GABA uptake, resulted in selective elevations in extracellular GABA in the three regions studied. Conversely, perfusion with high-potassium, a depolarizing agent, resulted in significant elevations in not only extracellular GABA but also aspartate, glutamate, and taurine. Thus, microdialysis is a method which can be employed to assess and to pharmacologically manipulate extracellular amino acids in the rat brain. PMID- 1640814 TI - Congressional medical payments: then and now. PMID- 1640815 TI - Deeds, drugs, and dogs. PMID- 1640816 TI - University of Maryland Medical System: American medicine's first teaching facility reinvents the academic hospital. AB - The University of Maryland Medical School, established in 1807, focused on bedside teaching. This emphasis has continued and expanded through the growth of University Hospital and, ultimately, the University of Maryland Medical System, such that Maryland can now boast of a superb medical care system providing excellent medical education and research opportunities in a patient care setting. PMID- 1640817 TI - Aging and humoral immunity. AB - If human antibody responses undergo molecular shifts similar to those identified in mice, the appropriate immunization strategy for the elderly would be a passive administration of the protective antibody from young donors rather than an attempt to boost the individual's own response with a more potent vaccine, because the shifted immune system can no longer make the right kind of antibody. PMID- 1640818 TI - An overview of follicular development in the ovary: from embryo to the fertilized ovum in vitro. PMID- 1640820 TI - Pancreas transplants. PMID- 1640819 TI - Progress in understanding the nicotinic acetylcholine receptor function at central and peripheral nervous system synapses through toxin interactions. AB - The need to treat diseases affecting the nicotinic AChR is great, but therapeutic options are few. Through careful correlation of structure-activity relationships of AnTX analogs, we may ultimately be led to the development of diagnostic and therapeutic drugs with specific nicotinic agonist or antagonist activities in the central nervous system that would be of major importance in the treatment of Alzheimer's disease. PMID- 1640822 TI - MNA files comprehensive HIV legislation. PMID- 1640821 TI - Imaging case of the month. Alzheimer's disease. PMID- 1640823 TI - Do you know your responsibilities as a nurse? PMID- 1640824 TI - Lucy Lincoln Dworn Nursing History Society. Sister Amy: pediatric nurse, education, administrator, innovator. PMID- 1640825 TI - The staff nurses' guide for a JCAHO visit. PMID- 1640826 TI - Enabling professional nursing staff to conduct research. PMID- 1640827 TI - FDA safety alert: needlestick risks. PMID- 1640828 TI - Membrane-associated GTPases in bacteria. AB - Members of the GTPase superfamily are extremely important in regulating membrane signalling pathways in all cells. This review focuses on membrane-associated GTPases that have been described in prokaryotes. In bacteria, LepA and NodQ are very similar to protein synthesis elongation factors but apparently have membrane related functions. The amino acid sequences of FtsY and Ffh are clearly related to eukaryotic factors involved in protein secretion. Obg and Era are not closely related to any GTPase subgroup according to amino acid sequence comparisons, but they are essential for viability. In spite of similarities to well-studied eukaryotic proteins the signalling pathways of these cellular regulators, with the exception of NodQ, have not yet been elucidated. PMID- 1640829 TI - Inducible DNA repair and differentiation in Bacillus subtilis: interactions between global regulons. AB - The SOS response of Escherichia coli has become a paradigm for the study of inducible DNA repair and recombination processes in many different organisms. While these studies have demonstrated that the components of the SOS response appear to be highly conserved among bacterial species, as with most models, there are some significant variations. Perhaps the best example of this comes from an analysis of the SOS-like system of the developmental organism, Bacillus subtilis. Accordingly, the most striking difference is the complex developmental regulation of the SOS system as this organism differentiates into its competent state. In this review we have given an overview of the elements that comprise the SOS system of B. subtilis. Additionally, we have summarized our most recent findings regarding the regulation of this regulon. Using these results along with new findings from other laboratories we have provided provocative molecular models for the regulation of the B. subtilis SOS system in response to DNA damage and during competent cell formation. PMID- 1640830 TI - Cytotoxic activity of a recombinant chimaeric protein between Pseudomonas aeruginosa exotoxin A and Corynebacterium diphtheriae diphtheria toxin. AB - A segment of the exotoxin A gene of Pseudomonas aeruginosa, coding for the N terminal end of domain I and domain II of the toxin (ETA), was genetically fused to the diphtheria toxin gene of Corynebacterium diphtheriae, coding for the N terminal end of A fragment of diphtheria toxin (DT). The resulting hybrid protein (termed CED1) was produced in large amounts and exported to the periplasm in Escherichia coli. This chimaeric protein reacted with both anti-ETA and anti-DT antisera. Furthermore, the chimaeric protein displayed ADP-ribosylation activity and exhibited cytotoxicity to mouse 3T6 fibroblasts. These results demonstrated that the chimaeric protein is cytotoxic, and that the toxic potential of DTA can be selectively internalized and translocated via domains I and II of exotoxin A, which are thus sufficient to direct and translocate an enzymatically active heterologous polypeptide segment into the cytosol of sensitive cells. PMID- 1640831 TI - Transcriptional control of sex-pheromone-inducible genes on plasmid pAD1 of Enterococcus faecalis and sequence analysis of a third structural gene for (pPD1 encoded) aggregation substance. AB - The expression of several neighbouring genes on plasmid pAD1 that are necessary for conjugation depend on induction with sex pheromone cAD1. Analyses of transcripts by Northern blot hybridization demonstrated that the genes sea1 (encoding surface exclusion protein) and asa1 (encoding aggregation substance) are transcribed independently. Both genes are organized in different operons together with neighbouring open reading frames of unknown function. Several transcripts could be identified for sea1 and asa1. Their transcriptional start sites were determined by primer extension experiments, confirming the results of the Northern blot experiments. We also could identify sea1- and iad- (encoding an inhibitory peptide counteracting sex pheromone cAD1) specific transcripts which are expressed constitutively, but to a lower extent relative to induced conditions. In addition, we localized the asp1 gene coding for aggregation substance of sex pheromone plasmid pPD1 and determined its DNA sequence, which was found to be highly homologous to asa1 (aggregation substance gene of pAD1) and prgB (aggregation substance gene of pCF10). The structural genes were found to be organized more or less identically on the three sex-pheromone plasmids pAD1, pCF10, and pPD1, and to be highly conserved. Regions supposed to be of crucial importance for regulatory functions, however, were found to differ. We also could identify some conserved DNA motifs which might be potential target sites for transcriptional regulators. In combination these data allowed us to formulate a model for the regulation of sex-pheromone-inducible genes of plasmid pAD1. Its main statement is that only in the presence of cAD1 can the gene traE1 be transcribed. The positive regulatory factor TraE1 then can trigger expression of the structural genes sea1 and asa1. PMID- 1640832 TI - Ferrioxamine uptake in Yersinia enterocolitica: characterization of the receptor protein FoxA. AB - The gene for the high-affinity outer membrane ferrioxamine receptor FoxA of Yersinia enterocolitica was cloned in Escherichia coli K-12. A foxA mutant of Yersinia could be complemented by the cloned DNA fragment. The FoxA encoding region was sequenced and an open reading frame encoding 710 amino acids, including a signal sequence of 26 amino acids, was deduced. The mature FoxA protein consisted of 684 amino acids and had a molecular mass of 75,768 Da. FoxA shared 33% amino acid sequence homology with FhuA, the ferrichrome receptor of Escherichia coli. Based on the homologies with FhuA and other TonB-dependent receptors a topological model of FoxA is presented. PMID- 1640833 TI - Outer membranes of gram-negative bacteria are permeable to steroid probes. AB - The permeability of bacterial outer membranes was assayed by coupling the influx of highly hydrophobic probes, 3-oxosteroids, with their subsequent oxidation catalysed by 3-oxosteroid delta 1-dehydrogenase, expressed from a gene cloned from Pseudomonas testosteroni. In Salmonella typhimurium producing wild-type lipopolysaccharide, the permeability coefficients for uncharged steroids were 0.45 to 1 x 10(-5) cm s-1, and the diffusion appeared to occur mainly through the lipid bilayer domains of the outer membrane. These rates are one or two magnitudes lower than that expected for their diffusion through the usual biological membranes. The permeation rates were markedly increased (up to 100 times) when the lipopolysaccharide leaflet was perturbed either by adding deacylpolymyxin or by introducing mutations leading to the production of deep rough lipopolysaccharides. An amphiphilic, negatively charged probe, testosterone hemisuccinate, penetrated much more slowly than the uncharged steroids. Study of various Gram-negative species revealed that P. testosteroni, Pseudomonas acidovorans, and Acinetobacter calcoaceticus showed higher outer membrane permeability to steroid probes and higher susceptibility to hydrophobic agents such as fusidic acid, novobiocin and crystal violet relative to S. typhimurium and Escherichia coli. PMID- 1640834 TI - Characterization of the Escherichia coli codBA operon encoding cytosine permease and cytosine deaminase. AB - The nucleotide sequence of a 3.1 kb segment carrying the cytosine deaminase gene (codA) from Escherichia coli was determined. The sequence revealed the presence of two open reading frames, the first (codB) specifying a highly hydrophobic polypeptide and the second specifying cytosine deaminase. A two-codon overlap between the two reading frames indicates that they constitute an operon. Transcription of the operon was found to be regulated by exogenous purines. Polypeptides specified by each of the two reading frames were expressed in minicells, and the codB gene product was found to be highly enriched in the membrane fraction. Uptake experiments showed that the CodB protein is required for cytosine transport into the cell and that the intracellular accumulation of cytosine correlated with the codB gene dose. A topological model for the cytosine permease in the cytoplasmic membrane is proposed. PMID- 1640835 TI - The amino acid sequence of a Bacillus subtilis phosphoprotein that matches an orfY-tsr coding sequence. AB - Bacillus subtilis contains a 30 kDa protein which was phosphorylated during late vegetative growth and sporulation. The sequence for the N-terminal 16 amino acids was found to be identical to the predicted sequence for the N-terminus of a small open reading frame, orfY, but diverged from the predicted sequence thereafter. The orfY region was resequenced and contained one less adenine residue than previously reported, resulting in an open reading frame from within orfY through the entire coding region for tsr which follows orfY. The predicted orfY-tsr amino acid sequence showed 24% identity to Escherichia coli fructose-1,6-bisphosphate aldolase. Two mutants in the tsr region had 2-5% of wild-type aldolase and the nucleotide sequences showed missense mutations. These results indicate that orfY tsr encodes aldolase and should be renamed fba1. PMID- 1640836 TI - The Aeromonas hydrophila exeE gene, required both for protein secretion and normal outer membrane biogenesis, is a member of a general secretion pathway. AB - The Aeromonas hydrophila Tn5-751 insertion mutant L1.97 is unable to secrete extracellular proteins, and is fragile because of defective assembly of its outer membrane. A KpnI 4.1 kb fragment, which complements this mutant when supplied with an exogenous promoter, was isolated and sequenced. It contains two complete genes, exeE and exeF, plus fragments of two others and may form part of an operon. The exeE and exeF open reading frames encode 501-residue M(r) 55,882 and 388-residue M(r) 43,431 proteins, respectively. These genes were expressed in vitro and their initiation codons verified by deletion analysis. Tn5-751 had inserted near the centre of the exeE gene in the L1.97 strain. Subclones of the KpnI 4.1 kb fragment which contained only the exeE gene fully complemented the mutation, indicating that its function is required both for extracellular secretion and outer membrane assembly. ExeE and ExeF are highly similar to other proteins which have been shown to be involved in extracellular secretion, suggesting that an additional export apparatus beyond that required for inner membrane translocation may be part of the physiology of many Gram-negative bacteria. PMID- 1640837 TI - Expression of extracellular phospholipase from Serratia liquefaciens is growth phase-dependent, catabolite-repressed and regulated by anaerobiosis. AB - Many members of the genus Serratia synthesize and excrete a number of extracellular hydrolytic enzymes. One of these is the phospholipase A1 from Serratia liquefaciens, the expression of which is growth-phase-dependent. Through the use of gene fusions and primer extension analysis we show that the expression of phospholipase is subject to positive transcriptional regulation of a dual promoter system; one promoter positioned approximately 600bp upstream from the phlA gene is responsible for the induction of phospholipase expression under anaerobic conditions, and the other promoter positioned 50bp upstream from the phlA gene is subject to catabolite repression and induced during the transition from exponential to late log-phase of bacterial growth. On the basis of sequence homology and behaviour in the relevant Escherichia coli mutants, we suggest that distant promoter to be Fnr-controlled and the proximal phlA promoter to be a member of the FIbB-controlled flagellar-chemotaxis regulon. PMID- 1640838 TI - Compliance and quality in residential life. Rhetoric and realities in today's ICF/MR: control out of control. AB - Contrasts between the rhetoric of quality assurance and the realities of poor quality in today's ICFs/MR were explored. Comparative studies have shown that ICFs/MR provide the poorest quality of life for persons with mental retardation. The ICF/MR operational model was described here as paper-oriented, failure-based, and insensitive to the effects of its own practices. Recommendations, including the establishment of local control, a less-direct relation between funding and rule compliance, and alternate forms of program evaluation and monitoring, were made. PMID- 1640839 TI - Compliance and quality in residential life. From standards to compliance, to good services, to quality lives: is this how it works? AB - Licensing and certification of ICFs/MR can adversely affect individuals, distort the allocation of (and waste) scarce resources, and encourage community residences to become small institutions. At a home in Northern California, used as a case study, recent interest in active treatment has emphasized good paper rather than good service or quality lives. Several recommendations were offered to encourage responsive services in line with progressive values and the wants and needs of individuals with developmental disabilities. PMID- 1640840 TI - Compliance and quality in residential life. Analyzing the impact of regulations on residential ecology. AB - Viewed from a behavior analytic perspective as a form of verbal behavior, regulatory rules affect the behavior of service providers in residential programs directly and indirectly; they can facilitate habilitative services or exert a powerful counter-habilitative influence. Because regulations are written to apply to the general case, regulatory rules tend to become decontextualized, often failing to address (a) the needs of individuals and (b) specific environmental circumstances. Ecobehavioral analysis of rule-governed behavior in residential settings can provide a means of understanding and measuring the effects of regulatory rules. Feedback from field settings about the effects of regulatory rules on the behavior of people who live and work in residential settings would help to recontextualize the rule-making process and promote better correspondence between the intended effects of regulations and their actual effects. PMID- 1640841 TI - Compliance and quality in residential life. Limitations of regulations as a means of social reform in developmental services. AB - It has become obvious that community care systems for people with developmental disabilities are not fully realizing some of the stated goals toward which they are directed, despite great process. The foundations and processes by which state agencies regulate and whether the regulatory process can be directed to issues affecting the quality of life of people receiving developmental services were explored. Limitations and side effects of regulations were discussed with respect to the unpredictability of long-term effects, problems in measuring compliance, economic rather than social focus, the changing state of knowledge, and special considerations associated with the field of developmental services. PMID- 1640842 TI - Receptor-dependent and -independent catabolism of low-density lipoprotein in a kindred with familial hypobetalipoproteinemia. AB - Three affected members of a kindred with asymptomatic hypobetalipoproteinemia (HBL) were injected intravenously with 125I-labeled native low-density lipoproteins (LDL) and 131I-labeled cyclohexanedione (CHD)-treated LDL. Plasma and urine radioactivity data were collected for 15 days at regular intervals. A compartmental model using the SAAM program was built to fit simultaneously 125I and 131I plasma radioactivity decay and urine excretion data. This model allows precise calculation of the kinetic parameters of both receptor-independent (NR) and receptor-dependent (R) pathways. Compared with normal subjects, HBL patients show a 90% increased fractional catabolic rate (FCR) of LDL by both routes, more marked for the R pathway (215% increase), and an approximately 50% reduced production rate (PR). Structural analysis did not show significant abnormalities of apolipoprotein (apo) B in HBL patients compared with normal. These data suggest that the very reduced, LDL-apo B plasma levels result from a combination of two processes: (1) an increased activity of all catabolic routes, and (2) a reduced "synthesis" rate. The latter may result from a decreased conversion of very-low-density lipoprotein (VLDL) to LDL secondary to an increased direct removal of large VLDL, suggested by apo C-II and C-III turnover studies previously reported. PMID- 1640843 TI - beta-Endorphin and cortisol abnormalities in spinal cord-injured individuals. AB - Plasma beta-endorphin-like immunoreactivity (BEP-ir) and cortisol levels were measured by radioimmunoassay (RIA) in nine patients who were at least 12 months status post spinal cord injury (SCI). Plasma levels were obtained at 8:00 am and 4:00 pm to determine circadian rhythm, and on the day following administration of 1 mg dexamethasone, levels were again obtained at 8:00 am and 4:00 pm. The mean morning levels of plasma BEP-ir were significantly lower than control values for this laboratory (6.2 +/- 1.2 v 12.0 +/- 2.3 pg/mL). The morning BEP-ir values were lowest in patients who were closer to the time of injury (described by a second-order polynomial regression, R = .89; P less than .01). Mean morning cortisol levels were not significantly different from controls, but showed greater variability (mean, 15.1; range, 0.7 to 22.7 micrograms/dL v control, 15.5; range, 7 to 35). Dexamethasone suppressed cortisol secretion in all patients and BEP-ir levels in six of nine patients. Failure to detect BEP-ir suppression occurred in patients whose BEP-ir levels were less than 4.5 pg/mL and close to the minimum detection limit of the assay. Depression was present in five of nine patients as measured by the Beck Depression Inventory (BDI) and in three of nine patients as measured by the Hamilton Depression Scale (HSRD). However, the depression indices did not correlate with the neuroendocrine measures. PMID- 1640844 TI - Thermic effect of epinephrine: a role for endogenous insulin. AB - The contribution of the basal insulin concentration to the metabolic response to epinephrine was measured in eight, postabsorptive, healthy volunteers before and during epinephrine (0.05 micrograms/kg fat-free mass [FFM] x min) and somatostatin (500 micrograms/h) infusion with and without insulin (0.1 mU/kg body weight [BW] x min) replacement. At basal plasma insulin concentrations, epinephrine increased oxygen consumption, heart rate, heart work, hepatic glucose production, glycogen breakdown in liver and muscle, and glucose oxidation, and the arterial plasma concentrations of glucose, lactate, and free fatty acids. Similar effects were observed during hypoinsulinemia, but epinephrine's actions on oxygen consumption and plasma concentrations of free fatty acids were disproportionally enhanced. We conclude that epinephrine-induced thermogenesis is partially inhibited by basal plasma insulin concentrations. PMID- 1640845 TI - Pravastatin lowers serum cholesterol, cholesterol-precursor sterols, fecal steroids, and cholesterol absorption in man. AB - Serum lipids, and absorption, intestinal fluxes, fecal elimination, and synthesis of cholesterol were studied before and during 4 weeks of pravastatin treatment at a dose of 40 mg/d in heterozygous familial hypercholesterolemic (FH) patients without (control group, n = 7) and with an ileal bypass (IBP group, n = 6). The drug reduced serum total and low-density lipoprotein (LDL) cholesterol and LDL apoprotein (apo)B levels up to 34%. Less-consistent decreases in intermediate density lipoprotein (IDL) and very-low-density lipoprotein (VLDL) cholesterol were also seen. None of the control patients and two of the IBP patients became normolipidemic (LDL less than 4 mmol/L). Marked transient reductions in serum free-methylated-cholesterol precursors, and more-constant decreases in the esterified and total fractions, suggested that cholesterol synthesis was reduced shortly after the start of treatment. The decreases in total lathosterol and methylsterols were more extensive in the IBP group than in the control group. Serum plant sterol levels were slightly increased, with inconsistent elevations of cholestanol. Reduced fecal elimination of cholesterol and its precursors suggests that decreased cholesterol synthesis was mainly due to lowered bile acid production, particularly in the IBP group with markedly enhanced basal bile acid and cholesterol synthesis. The serum and fecal levels of cholesterol precursors, lathosterol in particular, were related to each other and were proportionate to the serum level and fecal elimination of cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640846 TI - Metabolism of very-low-density lipoprotein triglyceride by human placental cells: the role of lipoprotein lipase. AB - Several studies have shown lipoprotein lipase (LPL) activity in human placenta, but the quantitative significance and cellular specificity of LPL in this organ are unknown. The objective of this report is to investigate the metabolism of very-low-density lipoprotein triglycerides (VLDL-TG) by the placenta, the role of LPL in this process, and the types of cells involved. Placental cells were obtained by enzymatic digestion (collagenase, hyaluronidase, and DNA-ase) and separated on a 40% Percoll gradient. The trophoblasts were the predominant cell type (80% to 85% pure) isolated at d = 1.033 to 1.048 and macrophages were predominant at d = 1.077 to 1.100 (greater than 95% pure), as characterized by eight immunocytochemical assays using cell protein-specific monoclonal antibodies. Macrophages represented 50% to 60% of cells isolated, and trophoblasts, 40% to 50%. LPL activity was assessed by VLDL-TG hydrolysis in primary 3- to 4-day tissue culture. In a representative experiment, LPL activity (nmol fatty acids (FA)/mg protein/24 h) was 101.3 +/- 5.3 in macrophages and 29.9 +/- 6.5 in the predominant trophoblast cell types, with approximately 20% of these amounts incorporated and reesterified. VLDL-TG hydrolysis and cell lipid uptake in both placental cell types was essentially abolished by a monoclonal anti-LPL antibody. When compared with a model of hepatocytes (Hep G2 cells), the hydrolysis of VLDL-TG was almost undetectable in these cells. In contrast, free fatty acids (FFA) uptake by Hep G2 cells was fourfold to sixfold greater than that by macrophages and trophoblasts, respectively. In conclusion, macrophages and trophoblasts are the two predominant placental cells isolated by enzymatic digestion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640847 TI - Effects of morbid obesity on insulin clearance and insulin sensitivity in several aspects of metabolism as assessed by low-dose insulin infusion. AB - Obesity is associated with impaired insulin action in glucose disposal, but not necessarily in other aspects of intermediary metabolism or insulin clearance. Sixteen morbidly obese and 14 normal-weight subjects (body mass index, 51.2 +/- 11.5 v 22.1 +/- 2.2 kg.m-2; mean +/- SD) were studied with sequential, low-dose, incremental insulin infusion with estimation of glucose turnover. In obese patients, basal plasma insulin was higher (10.5 +/- 3.8 v 2.4 +/- 3.0 mU.L-1, P less than .001) and remained elevated throughout infusion (F = 492, P less than .001), as did C-peptide (F = 22.7, P less than .001). Metabolic clearance rate for insulin (MCRI) at the highest infusion rate was similar (1,048 +/- 425 v 1,018 +/- 357 mL.m-2.min-1, NS). Basal hepatic glucose production in obese subjects was less than in normal-weight subjects (270 +/- 108 v 444 +/- 68 mumol.m-2.min-1, P less than .01), as was the basal metabolic clearance rate for glucose (MCRG, 77 +/- 26 v 108 +/- 31 mL.m-2.min-1, P less than .05). Insulin infusion caused blood glucose to decrease less in the obese patients (1.4 +/- 0.5 v 1.9 +/- 0.5 mmol.L-1, P less than .05); hepatic glucose production was appropriately suppressed in them by hyperinsulinemia, but their insulin-mediated glucose disposal was reduced (1.67 [0.79] v 4.45 [2.13] mL.m-2.min-1/mU.L-1, P less than .01). Concentrations of nonesterified fatty acids (NEFA), glycerol, and ketones were elevated throughout the insulin infusions in obese patients, despite the higher insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640848 TI - Vitamin E restores reduced prostacyclin synthesis in aortic endothelial cells cultured with a high concentration of glucose. AB - Reduced prostacyclin (PGI2) production by the vascular wall may play an important role in the pathogenesis of vascular lesions such as atherosclerosis. The present study was undertaken to evaluate the effect of vitamin E on the production of PGI2 and other prostaglandins (prostaglandin E2 [PGE2], thromboxane A2 [TXA2], and 15-hydroxyeicosatetraenoic acid [15-HETE]) by bovine aortic endothelial cells cultured in a high concentration of glucose (300 mg/dL). Compared with endothelial cells cultured in 100 mg/dL glucose, the production of PGI2 and other prostaglandins, except 15-HETE, was significantly reduced in cultures containing 300 mg/dL glucose when stimulated by histamine, the Ca2+ ionophore, A23187, or human plasma-derived serum (PDS). The addition of vitamin E to each stimulant significantly restored the production of PGI2, PGE2, and TXA2, products of the cyclo-oxygenase pathway, in aortic endothelial cells cultured in 300 mg/dL glucose. This effect of vitamin E on the stimulation of prostaglandin production was generally specific for D-alpha-tocopherol, but not for the other vitamin E analogs tested. However, vitamin E and the stimulants had no effect on the production of 15-HETE, a product of the lipoxygenase pathway. Moreover, vitamin E alone, without stimulants, did not affect prostaglandin production in cultured bovine aortic endothelial cells. These results suggest that vitamin E may restore reduced PGI2, PGE2, or TXA2 production by bovine aortic endothelial cells cultured in a high concentration of glucose. It seems likely that vitamin E may restore depressed PGI2 production by the vascular wall in hyperglycemic conditions such as those seen in patients with diabetes mellitus. PMID- 1640849 TI - Effect of chromium administration on glucose tolerance in stroke-prone spontaneously hypertensive rats with streptozotocin-induced diabetes. AB - The present study was conducted to assess the effect of chromium (Cr) administration on glucose tolerance in insulin-dependent diabetes that accompanies hypertension. Four rat groups were used: stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar Kyoto rats (WKY) with and without streptozotocin (SZ, 40 mg/kg)-induced diabetes. Each group of rats was subdivided to the Cr-dose group and the control group. The Cr-dose group, which was intraperitoneally administered Cr solution (20 micrograms trivalent chromium/kg body weight/d for 4 weeks), and the control group (saline) were studied for plasma glucose and plasma insulin during intraperitoneal glucose tolerance test (IPGTT) and insulin action by isolated adipocytes. For diabetic SHRSP showing the highest plasma glucose and lowest plasma insulin among the four groups, Cr administration led to the greatest reduction in plasma glucose without a significant effect on plasma insulin during IPGTT. For each diabetic WKY and normal SHRSP and WKY, those given Cr showed lower levels of plasma glucose with lower levels of plasma insulin than the controls. For diabetic SHRSP, glucose uptake by isolated adipocytes in the Cr-dose group was higher than that in the control group. This effect of Cr administration involved enhancement of insulin responsiveness and sensitivity, attributed to enhanced affinity of the insulin receptor. A similar tendency was observed for diabetic WKY. However, for normal SHRSP and WKY, the increase in glucose uptake due to Cr administration coincided only with enhanced insulin responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640850 TI - Effect of leucine on amino acid and glucose metabolism in humans. AB - Leucine has been reported to be an important regulator of protein metabolism. We investigated the effect of intravenous infusion of L-leucine versus saline on amino acid metabolism in eight healthy human subjects. Plasma concentrations of amino acids were measured and protein turnover was estimated using L-(1 13C)lysine and L-(3,3,3,-2H3)leucine as tracers. Glucose kinetics were measured using D-(6,6-2H2)glucose as a tracer. Leucine infusion increased the plasma leucine concentration from 103 +/- 8 to 377 +/- 35 mumol/L (P less than .01). Plasma concentrations of essential amino acids, including threonine, methionine, isoleucine, valine, tyrosine, and phenylalanine were significantly decreased by leucine infusion. Leucine infusion did not change lysine flux significantly (108 +/- 4 during saline v 101 +/- 4 mumol/kg/h-1 during leucine infusion), but decreased lysine oxidation (13.2 +/- 0.9 v 10.7 +/- 1 mumol/kg/h, P less than .05) and endogenous leucine flux (from 128 +/- 4 to 113 +/- 7 mumol/kg/h, P less than .05) when plasma (2H3) ketoisocaproate (KIC) was used for calculation. During leucine infusion, the (2H3) KIC to (2H3) leucine plasma enrichment ratio increased from 0.76 +/- 0.02 to 0.88 +/- 0.01 (P less than .001), while estimation of leucine flux using plasma (2H3) leucine showed no change in endogenous leucine flux. Leucine infusion decreased hepatic glucose production and metabolic clearance of glucose, but did not change plasma concentrations of glucose, insulin, C-peptide, glucagon, epinephrine, norepinephrine, or free fatty acids. We conclude that leucine spares glucose and lysine catabolism and decreases plasma concentrations of essential amino acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640851 TI - Effect of intensive endurance training on lipoprotein profiles in young and older men. AB - Although there are considerable data concerning the effects of endurance exercise training (ET) on plasma lipoproteins, the results have been quite inconsistent. The observed variability of response may be related to the age, sex, adiposity, or diet of the subjects tested, or to the type and intensity of the exercise intervention. Furthermore, there is relatively little such data in older individuals. Therefore, in the present study, we investigated the effects of intensive ET on lipoprotein profiles in healthy young (n = 12; 28.2 +/- 2.4 years) and older (n = 15; 67.5 +/- 5.8 years) men. Unlike subjects in most similar studies, our subjects were weight-stabilized on a constant-composition diet for 21 days prior to determination of the lipoprotein profile before and after the ET program. At baseline, the two groups were not significantly different with respect to any individual component of their lipoprotein profiles, relative weight, or percent body fat, but the older men had a more central distribution of fat by both waist to hip ratio (WHR) and computed tomography (CT). Maximal aerobic power, expressed per kilogram of body weight (VO2 max), was 33% lower (P less than .001) in the older men at baseline. Following the 6-month, walk/jog/bike ET program (5 d/wk), both the young (+18%, P less than .001) and the older (+22%, P less than .001) men increased their VO2 max. This was associated with small, but significant, decrements in weight, percent body fat, and WHR only in the older men.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640852 TI - Age-related increase of collagen fluorescence in human subcutaneous tissue. AB - Nonenzymatic glycation produces compounds with characteristic fluorescence in long-lived proteins. We recently described the influence of age in rat collagen linked fluorescence. To examine the effect of age in humans, we studied the subcutaneous collagen-linked fluorescence in samples from 26 subjects of both sexes (age range, 42 to 78 years) who were undergoing vascular surgery. Intensity of fluorescence at 385 nm (upon excitation at 335 nm) and 440 nm (upon excitation at 370 nm) increased exponentially with age (r = .827, y = 114 + e0.038x, P less than .001; and r = .905, y = 36 + e0.039x, P less than 0.001, respectively). The two sets of data exhibited a high degree of correlation (r = .980, P less than .001, n = 26). Age-adjusted fluorescence data did not correlate with sex, body weight, or type of vascular pathology. The collagen fluorescence accumulation rate was 3.7% per year, and the characteristic time (CT) was 26 to 27 years. We conclude that the fluorescence measurement is a reliable methodology that can be used as a marker for biological age until new, more-specific tools are available. PMID- 1640853 TI - Metabolic changes during treatment with valproate in humans: implication for untoward weight gain. AB - This study was initiated to elucidate the mechanisms behind valproate-induced weight gain. Eight patients with epilepsy were studied with identical examination programs before and during the end of the first month of treatment with sodium valproate (VPA). The measurements included registration of food intake, indirect calorimetry, and determination of pancreatic and thyroid hormones, catecholamines, albumin, electrolytes, glycerol, and free fatty acids. Measurements were performed both at the basal condition and during a 3-hour oral glucose tolerance test (OGTT). After the start of VPA treatment, the mean levels during the OGTT of plasma glucose and catecholamines were significantly decreased by 7% and 25%, respectively (P less than .05). The mean ratio of insulin to glucagon decreased by 37% (P less than .01). During the glucose load, the decreases in free fatty acids were less pronounced after the start of VPA treatment, whereas the mean levels of glycerol were found to be unchanged. We detected no differences between the two periods with regard to total energy intake or macronutrient selection, energy expenditure, or thyroid hormones. As VPA is known to affect the concentration of carnitine in humans, it is hypothesized that a possible VPA-induced deficiency of the beta-oxidation of fatty acids is important for the development of obesity in epileptic patients in long-term treatment with VPA, but changes in catecholamines or other hormones might also be of importance. PMID- 1640854 TI - The effect of epinephrine on glucose-mediated and insulin-mediated glucose disposal in insulin-dependent diabetes. AB - The aim of this study was to determine the relative roles of changes in glucose mediated glucose disposal (SG) and insulin sensitivity (SI) on the impairment of glucose disposal caused by epinephrine (EPI) infusion in type I (insulin dependent) diabetes mellitus (IDDM). Seven non-obese young adult diabetics with minimal endogenous insulin secretion had EPI infusions at 25 ng/kg/min for 5.5 hours, after a basal overnight insulin infusion (12 mU/kg/h), and glucose infusion as required to maintain euglycemia. The EPI infusion produced approximately an eightfold increase in plasma EPI. At 2.5 hours, an intravenous glucose tolerance test (IVGTT) was performed with supplemental exogenous insulin infusion to achieve an approximation of normal endogenous insulin secretion. In random order, each subject also had a control (CTR) infusion of basal insulin before the IVGTT. The results were analyzed according to a modification of the minimal model of Bergman et al. EPI infusion was associated with (1) elevated basal plasma glucose (EPI v CTR, 9.8 +/- 0.3 SE v 7.7 +/- 0.7 mmol/L, P less than .05); (2) elevated plasma nonesterified fatty acids (NEFA, 0.9 +/- 0.1 v 0.3 +/- 0.1 mmol/L, P less than .05); and (3) profoundly reduced glucose disposal (KG 0.59 +/- 0.1 v 1.91 +/- 0.33 min-1 x 10(2), P less than .02). Further analysis showed that the reduced glucose disposal was attributable to a marked decrease in SI (EPI 0.9 +/- 0.5 v CTR 7.03 +/- 3.2 min-1.mU-1.L x 10(4), P less than .05) with no significant change in SG (EPI 2.5 +/- 0.2 v CTR 3.1 +/- 0.5 min-1 x 10(2), NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640855 TI - Increased insulin sensitivity and increased rates of insulin clearance in men with human immunodeficiency virus (HIV) infection. PMID- 1640856 TI - Alterations in levels of plasma phenylalanine and its catabolism in the liver of stressed rats. AB - This study examined the relationship between elevation of blood phenylalanine (Phe) concentrations often observed in trauma or infected patients without hepatic dysfunction and alterations of liver Phe catabolism. Rats underwent pathophysiologically different stresses, either sepsis or scald injury. The catalytic activity of hepatic Phe hydroxylase (PH) in the septic rats, as measured after preincubation with Phe, decreased to 60% of the control values; this in vitro result suggests a reduction of enzyme species activated by its substrate. Phe was degraded in the septic rats to a similar extent to that in controls, when measured by pulse administration of [1-14C]-Phe. In the scalded rats whose plasma Phe level showed a comparable but transient increase, no significant alterations occurred in Phe catabolism and enzyme activities. The changes in plasma glucagon and catecholamine levels were consistent with those of the enzyme activities involved in Phe and tyrosine (Tyr) catabolism in the stressed groups. These results indicate that inadequate activation of native PH by regulatory mechanisms involving Phe in vivo was also associated with the accumulation of plasma Phe in infected rats during massive mobilization of amino acids from muscles under conditions of enhanced and sustained catabolism. PMID- 1640857 TI - Possible role of glycogen accumulation in B-cell glucotoxicity. AB - Rat pancreatic islets cultured for 1 to 5 days in the presence of 20 to 80 mmol/L D-glucose accumulate glycogen in a time- and concentration-dependent manner. When the glycogen-rich islets are incubated for 6 to 10 minutes in the absence of D glucose, the rate of glycogenolysis is grossly proportional to the glycogen content. Exogenous D-glucose (7 to 20 mmol/L) inhibits glycogenolysis. This inhibitory effect opposes the increase in glycolytic flux attributable to the utilization of exogenous glucose. Both the inhibitory effect of D-glucose on glycogenolysis and the utilization of exogenous hexose tend to be higher with alpha- than with beta-D-glucose. In light of these findings, it is proposed that the interference of D-glucose with glycogenolysis might play a role in the paradoxical changes in insulin output and its altered anomeric specificity in response to D-glucose administration, as is often encountered in non-insulin dependent diabetic subjects and experimental models of B-cell glucotoxicity. PMID- 1640858 TI - Characterization of unprocessed insulin proreceptors in COS 7 cells transfected with cDNA with Arg735----Ser735 point mutation at the cleavage site. AB - We previously reported on patients with severe insulin resistance due to unprocessed insulin proreceptors. A structural change of the cleavage site from Arg-Lys-Arg-Arg to Arg-Lys-Arg-Ser due to G----T point mutation appeared to be the cause for failure to process the proreceptors. To determine whether the mutation of insulin proreceptors at the cleavage site was responsible for unprocessed insulin receptors and to elucidate the structural and binding characteristics of the proreceptors, we transfected cDNA with the mutation in COS 7 cells and examined the expressed insulin receptors. At 72 hours after transfection, insulin binding increased to the maximum in cells transfected with either normal or mutated cDNA, and insulin binding was 40 and 14 times higher than that of nontransfected cells, respectively. The declining rate of insulin binding after reaching the maximum was delayed in cells transfected with mutated cDNA. Affinity cross-linking and surface-labeling studies showed a 135-kilodalton (kD), normal alpha-subunit in the cells transfected with normal cDNA and a 210-kD proreceptor in the mutant cells. The proreceptors were cleaved by trypsin to yield normal-sized alpha- and beta-subunits. The sensitivity to trypsin was similar to that demonstrated in patients' cells, and the most effective concentration for the cleavage was 0.025%. Autophosphorylation resulted in decreased 32P incorporation into proreceptors of cells transfected with mutated cDNA at both basal and insulin-stimulated states, without a change in insulin sensitivity. Competitive binding studies with insulin, proinsulin, and miniproinsulin showed that the proreceptors had a lower relative affinity for proinsulin, but this characteristic disappeared after trypsin treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640859 TI - Ethanol stimulates apolipoprotein A-I secretion by human hepatocytes: implications for a mechanism for atherosclerosis protection. AB - Ethanol intake in humans has been shown to have a protective effect against coronary heart disease. The specific mechanism by which ethanol is cardioprotective has not been elucidated. Apolipoprotein (apo) A-I, the major protein of high-density lipoprotein (HDL), takes up cellular cholesterol, thus initiating reverse cholesterol transport whereby excess tissue cholesterol is eliminated. Using highly specific antibodies, we have found that ethanol increases apo A-I secretion and the incorporation of radiolabeled leucine into apo A-I by human hepatocytes (Hep-G2 cells). In addition, we have found that apo A-I molecules induced by ethanol have the ability to efflux cholesterol from human fibroblasts in vitro, and that apo A-I mass directly correlates with cholesterol efflux levels. At 10, 20, and 100 mmol/L, ethanol stimulated apo A-I secretion by 130%, 136%, and 162% of control, respectively (control, 3.71 micrograms apo A-I/micrograms DNA), also stimulating the incorporation of 3H leucine into newly synthesized apo A-I by 115%, 131%, and 159% of control (control, 111 cpm/micrograms DNA/h). The ethanol-induced apo A-I from Hep-G2 cells (incubated with 0, 10, 20, and 100 mmol/L ethanol) effluxed 2%, 14%, 16%, and 32% label (per h/mL incubation medium), respectively. Apo A-I mass correlated linearly with cholesterol efflux (r = .99, P less than .01). This data indicates that the cardioprotective role of moderate ethanol intake in humans is mediated by its stimulatory action on hepatic apo A-I secretion, thus defining the physiological basis for increased plasma apo A-I levels in vivo. PMID- 1640860 TI - Pulsatile activation of the hypothalamic-pituitary-adrenal axis during major surgery. AB - To examine the response of the hypothalamic-pituitary-adrenal (HPA) axis to severe surgical stress, we measured the immunoreactive plasma levels of corticotropin-releasing hormone (CRH), corticotropin, cortisol, arginine vasopressin (AVP), atrial natriuretic factor (ANF), neuropeptide Y (NPY), interleukin-1 (IL-1), IL-6, interferon gamma (INF), and tumor necrosis factor alpha (TNF-alpha) in eight patients with Zollinger-Ellison syndrome (ZES) or mediastinal parathyroid carcinoma, all undergoing major surgery with a standardized anesthetic technique. Blood samples were drawn the morning before surgery, every 10 to 30 minutes throughout surgery (average, 308.7 +/- 15 minutes), and every morning for the next 4 postoperative days (POD). During surgery, plasma CRH concentrations were slightly but not significantly elevated compared with those before surgery and with those of the next 4 POD. However, the values were within the normal range (less than 2.2 pmol/L) and showed 8.9 +/- 0.6 pulses (one pulse every 34.7 +/- 1.6 minutes). Plasma corticotropin, on the other hand, was quite elevated, but was also released in a pulsatile fashion during the surgical procedure (one pulse every 36.7 +/- 1.6 minutes). Most of these secretory episodes of corticotropin were temporally related to those of CRH. Corticotropin returned to basal levels on the first POD and remained so for all 4 POD. Plasma cortisol concentrations increased steadily during surgery and remained elevated the first POD. Cortisol showed 6.2 +/- 1.1 pulses during the operative sampling period (one pulse every 71.8 +/- 13 minutes). Plasma AVP concentrations were also markedly elevated during surgery, but individual secretory pulses were not detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640861 TI - A high-fat diet worsens metabolic control in streptozotocin-treated rats by increasing hepatic glucose production. AB - The aim of this study was to determine the mechanism by which a high-fat diet exacerbates the diabetes produced by a low dose of streptozotocin (STZ). The glucose clamp technique was used to determine hepatic glucose production (HGP) and the disappearance rate (Rd) of glucose, basally and during insulin infusions of 1.0 and 3.0 mU/kg/min in control of STZ-treated rats fed either a low-fat or high-fat diet. Fasting plasma glucose in the high fat-STZ (HFS) group was significantly higher than in any of the other groups: low fat-STZ (LFS), high-fat controls (HFC), or low-fat controls (LFC) (18.1 +/- 1.6 v 8.1 +/- 0.8 mmol/L, P less than .001; 6.0 +/- 0.2 mmol/L, P less than .001; 5.4 +/- 0.1 mmol/L, P less than .001, respectively). Basal HGP was markedly higher in the HFS group compared with each of the other three groups (98.8 +/- 5.9 v 61.4 +/- 3.7, P less than .001; 42.9 +/- 1.6, P less than .001; 39.6 +/- 1.3 mumol/kg/min, P less than .001; HFS v LFS, HFC, and LFC, respectively). Following insulin infusion, no differences were observed in HGP between the LFC and LFS groups at either insulin dose. However, HGP was not suppressed to control levels in either of the high-fat diet groups, and this defect was more marked in the HFS group. It is concluded that a high-fat diet exacerbates mild STZ diabetes primarily by increasing HGP. PMID- 1640862 TI - Racial differences in lipid and lipoprotein levels in diabetes. AB - Racial differences in plasma lipid and lipoprotein levels were investigated in 145 patients with non-insulin-dependent diabetes mellitus (NIDDM). Black men had higher high-density lipoprotein (HDL) cholesterol levels, lower triglyceride levels, and an improved atherogenic index compared with white men. Premenopausal black women were also found to have higher HDL cholesterol levels, lower triglyceride levels, and a lower atherogenic index than their white counterparts. Adjustment for age, waist to hip ratio (WHR), hemoglobin A1c (HbA1c), and physical activity did not eliminate the significant differences found. There were no racial differences found regarding total and low-density lipoprotein (LDL) cholesterol. Metabolic control as measured by HbA1c was significantly correlated with the triglyceride level in black women. These data confirm that racial differences exist in plasma lipid levels among patients with NIDDM. PMID- 1640863 TI - Effect of a moderate alcohol intake on the lipoproteins of normotriglyceridemic obese subjects compared with normoponderal controls. AB - Moderate alcohol intake is frequently associated with an elevated concentration of high-density lipoprotein (HDL), which is one of the potential causes for the relative decrease in cardiovascular risk reported in moderate drinkers. Conversely, low HDL concentrations, particularly HDL2, in obese subjects may be a risk factor. The effect of 30 g alcohol daily (wine) during 14 days following a period of abstinence was studied in seven normolipidemic obese subjects (body mass index [BMI], 30 +/- 1.7 kg/m2) compared with seven normoponderal controls (BMI, 22 +/- 1.2 kg/m2). Alcohol caused apolipoprotein (apo) AI and apo AII concentrations to increase in all controls by 12% and 16% (P less than .05), but not in obese subjects. Lipoprotein (Lp) AI HDL particles (without AII) were initially in the same proportions in the two groups. Their increase in controls only (P less than .03) was not matched by an increase in HDL2 in all subjects. In obese subjects, neither Lp AI nor HDL2 were increased by alcohol, but their HDL triglyceride (TG) contents, initially elevated, were normalized. Cholesterol ester (CE) transfer activity was not different in controls and obese subjects during abstinence (105.7 +/- 40.8 v 104.8 +/- 34.5 mmol/mg protein/h). It was notably depressed by alcohol in controls (74.2 +/- 27.4, P less than .002), but not in obese subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640864 TI - Estimation of plasma glucose fluctuation with a combination test of hemoglobin A1c and 1,5-anhydroglucitol. AB - We investigated the effect of plasma glucose fluctuation on hemoglobin A1c (HbA1c) and plasma 1,5-anhydroglucitol (AG) levels, especially in insulin dependent diabetes mellitus (IDDM). Plasma AG is a new marker that provides sensitive and analytical information on glycemic control. The basic mechanisms underlying both the reduction and recovery of the plasma AG level, ie, the excretion into urine with glucosuria and the amount supplied to the body, were presumed to be similar in IDDM and non-insulin-dependent diabetes mellitus (NIDDM) patients. The correlation coefficient for mean plasma glucose and AG was .591, and it was .578 for mean plasma glucose and HbA1c in IDDM patients. In NIDDM, the correlation between mean plasma glucose and AG was -.869, and between mean plasma glucose and HbA1c, .875. The plasma AG levels in the IDDM group showed a lower range than in the NIDDM group, even with similar HbA1c levels. All the cases showing lower plasma AG levels among those with similar HbA1c levels manifested greater fluctuation of plasma glucose and a larger amount of urinary glucose. The lower AG level in IDDM patients was reversible to the level in NIDDM patients when the greater fluctuation of plasma glucose was corrected. Thus, it was suggested that because urinary glucose excretion is intermittently high in IDDM patients, plasma AG is frequently low, even though the mean plasma glucose and HbA1c levels suggest good control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640865 TI - Postprandial thermogenesis at rest and postexercise before and after physical training in lean, obese, and mildly diabetic men. AB - To determine the independent impact of physical training on postprandial thermogenesis at rest and after 1 hour of cycling at 100 W, 10 lean (15% +/- 1% body fat), 10 obese (33% +/- 2% fat), and six obese diet-controlled, type II diabetic men (34% +/- 4% fat) underwent 12 weeks of vigorous cycle ergometer training (4 h/wk at approximately 70% of maximum oxygen consumption [VO2max]) while maintaining body weight and composition. Body weight was held constant by refeeding the energy expended in each training session. Cardiorespiratory fitness increased by approximately 27%, but body weight and fat did not change. Before and at least 4 days after the last exercise session, energy expenditure was measured for 3 hours under four conditions: (1) rest, no meal; (2) rest, after a 720-kcal mixed meal; (3) postexercise after 1 hour cycling, no meal; and (4) postexercise, meal after exercise. The thermic effect of food was calculated as postprandial minus postabsorptive energy expenditure at rest and postexercise (kcal/3 h). Before and after training, the thermic effect of food during rest was lower in obese than in lean men, and lower in diabetic than in obese men (P less than .05). Thermogenesis was improved after short-term exercise in obese and diabetic men compared with that at rest, but was not normalized (P less than .05 for lean v obese, diabetic men). A significant effect of training on thermogenesis was due to a small but significant increase after training for diabetic men under the postexercise condition. Thus, while short-term exercise enhances but does not normalize thermogenesis in obese and diabetic men, long term exercise training leading to increased cardiorespiratory fitness, in the absence of changes in body composition, leads to a small increase in thermogenesis in diabetic men, which manifests only after a short period of exercise. PMID- 1640866 TI - Differences in metabolism of time-release and unmodified nicotinic acid: explanation of the differences in hypolipidemic action? AB - The possibility that differences in metabolism might underly the differences in efficacy and toxicity between time-release and unmodified formulations of nicotinic acid was investigated by measuring 24-hour urinary excretion of metabolites in 10 subjects who received both forms. Nicotinic acid has two metabolic fates: formation of nicotinamide adenine dinucleotide (NAD) and formation of nicotinuric acid, the glycine conjugate of nicotinic acid. Catabolism of NAD releases nicotinamide, which is subsequently methylated and/or oxidized to form a number of metabolites, with 2-pyridone predominating. Excretion of nicotinuric acid was more than four times greater when subjects took unmodified nicotinic acid than when they took time-release nicotinic acid (78.2 and 18.8 mg, respectively). In contrast, excretion of 2-pyridone with unmodified nicotinic acid was only 30% more than with time-release nicotinic acid (171.0 and 129.9 mg, respectively). These results demonstrate a marked difference in the metabolism of unmodified and time-release nicotinic acid. It is proposed that nicotinyl coenzyme A (CoA), the metabolic intermediate in the formation of nicotinuric acid, mediates some of the hypolipidemic actions of nicotinic acid, as the acyl-CoA esters of xenobiotics, including clofibrate, have been shown to interfere with lipid metabolism. PMID- 1640867 TI - Cortisol secretion in relation to body fat distribution in obese premenopausal women. AB - Urinary cortisol output and serum cortisol concentrations were measured in the steady state, under "field" conditions, and during standardized inhibitory and stimulatory tests in premenopausal, obese women, and were analyzed in relation to adipose tissue distribution. Urinary cortisol output was increased under field conditions in women with an elevated waist to hip circumference ratio (WHR) and, in particular, in women with a large abdominal sagittal diameter, indicating visceral fat accumulation. However, dexamethasone inhibition of cortisol secretion was normal. Stimulation with corticotropin analogue and with physical (cold-pressor test) or mental (color-word or mathematic) stress tests also showed elevated responses of serum cortisol, but not of prolactin or growth hormone concentrations. It is suggested that women with visceral fat accumulation have elevated cortisol secretion due to an increased sensitivity along the hypothalamic-pituitary-adrenal axis, and that this may be causing their abnormal fat depot distribution. PMID- 1640868 TI - Experimental study on Reye's syndrome: inhibitory effect of interferon alfa on acetylsalicylate-induced injury to rat liver mitochondria. AB - Viral infection and acetylsalicylate (ASA)-induced mitochondrial aberration have been reported to play important roles in the pathogenesis of Reye's syndrome. We report that increasing amounts of ASA (0 to 250 mumol/L) resulted in increases in state 4 respiration and decreases in state 3 respiration in rat liver mitochondria in vitro when using alpha-ketoglutarate and/or beta-hydroxybutyrate as respiratory substrates, but not when using succinate as substrate. Interferon alfa (IFN-alpha) (1.5 to 5 x 10(4)IU/mL, approximately 1/100 the therapeutic dosage for humans) and interleukin-1 (IL-1) (1.5 to 2 x 10(4)IU/mL, nearly equivalent to the therapeutic dosage) decreased the severity of the above effects via interaction with mitochondrial membranes. Interferon gamma (IFN-gamma) and interleukin-2 (IL-2) had no such protective effect. Electron microscopic observation indicated that IFN-alpha prevented the induction of mitochondrial swelling by ASA. These results suggest that IFN-alpha may prove to be effective for the treatment of Reye's syndrome. PMID- 1640869 TI - Generalized lipodystrophy: in vivo evidence for hypermetabolism and insulin resistant lipid, glucose, and amino acid kinetics. AB - Stable isotope tracers and indirect calorimetry were used to evaluate whole-body energy, glucose, lipid, and amino acid metabolism in a patient with generalized lipodystrophy during basal conditions and in response to insulin therapy. The results were compared with those obtained in previous studies in normal volunteers. The basal rate of glucose production (33.7 mumol/kg.min) was three times higher than normal. The basal rate of glycerol appearance in blood, an index of lipolysis, was 60% greater than normal when expressed per kilogram body weight (3.82 mumol/kg.min), but was more than 10 times normal when expressed per kilogram body fat mass (123.2 mumol/kg.min) because of the marked decrease in body fat in our patient (3% of total body weight). Leucine rate of appearance, an index of protein breakdown, and nonoxidative leucine disposal, an index of protein synthesis, were also greater than normal. Resting energy expenditure (REE) was 30% greater than normal. The effect of insulin infusion on these metabolic parameters was markedly blunted. These metabolic abnormalities help explain many of the clinical findings such as hyperglycemia, hypertriglyceridemia, fat depletion, hepatomegaly, and steatosis observed in patients with lipodystrophy. Ineffective insulin function in many tissues appears to be an important factor in the pathophysiology of lipodystrophy. PMID- 1640870 TI - Evidence that glucose transport is rate-limiting for in vivo glucose uptake. AB - To determine whether glucose transport or intracellular glucose metabolism is rate-limiting for in vivo glucose uptake, rates of glucose disposal were measured in a group of normal subjects at varying levels of hyperglycemia designed to attain saturating rates of glucose disposal at low and high physiological insulin concentrations. At insulin levels of approximately 200 pmol/L, glucose disposal rates were 2.9 +/- 0.4, 4.7 +/- 0.5, 6.4 +/- 0.6, and 6.5 +/- 0.8 mg/kg/min at plasma glucose concentrations of 5.55, 11.10, 13.88, and 19.43 mmol/L (or 100, 200, 250, and 350 mg/dL, respectively). At insulin levels of approximately 750 pmol/L, glucose disposal rates were 1.7 to 2.1-fold higher: 6.2 +/- 0.7, 9.2 +/- 1.1, 11.0 +/- 1.1, and 12.3 +/- 1.4 mg/kg/min at glucose levels of 5.55, 11.10, 13.88, and 19.43 mmol/L. Thus, during both the 15- and 40-mU/m2/min insulin infusions, glucose disposal increased in a linear fashion from 5.55 to 13.88 mmol/L (r = .90) and then effectively plateaued at the same plasma glucose level. If the plateau of glucose disposal during the 40-mU/m2/min insulin infusion was due to saturation of the intracellular capacity to metabolize glucose, then when plasma glucose was increased from 13.88 to 19.43 mmol/L at the lower insulin level, the glucose disposal should have continued to increase and not plateau, since the rate of glucose disposal was only approximately 50% of that attained at the higher insulin infusion rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640871 TI - Hyperinsulinemia and human chorionic gonadotropin synergistically promote the growth of ovarian follicular cysts in rats. AB - Tonically elevated serum luteinizing hormone (LH) and hyperinsulinemia are prominent features of polycystic ovary syndrome (PCO) in women, but the relative roles of LH and insulin in the pathogenesis of PCO is still unknown. The present study was undertaken to determine the effect(s) hyperinsulinemia might have on the induction of follicular cysts by LH/human chorionic gonadotropin (hCG) in the rat. Beginning on day 85 of age, adult female rats were given one of the following in vivo treatments: (1) vehicle alone; (2) a high-fat diet to control for the effects of weight-gain; (3) up to 6 U insulin per day; (4) 50 micrograms gonadotropin-releasing hormone (GnRH) antagonist (GnRHant) per day; (5) 1.5 IU hCG twice daily; (6) insulin + hCG; (7) insulin + GnRHant; (8) hCG + GnRHant; or (9) hCG + insulin + GnRHant. After 22 days of treatment, animals were killed on day 23, trunk blood was collected, and ovaries were excised for histological study. Regular cycles, assessed by vaginal smears, ceased after 10 days for most animals in treatment groups receiving hCG, but continued in all other treatment groups. All the animals in each hCG-treated group developed either unilateral or bilateral cystic ovaries, while no animals in the groups not receiving hCG developed follicular cysts. More animals from each group treated with both hCG and insulin possessed bilateral ovarian cysts than did rats treated with hCG alone: 80% and 60%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640872 TI - Influence of aerobic capacity, body composition, and thyroid hormones on the age related decline in resting metabolic rate. AB - It has been suggested that changes in fat-free weight may not fully explain the decline of resting metabolic rate (RMR) that occurs with aging. We therefore examined the hypothesis that a reduction in maximal aerobic capacity (VO2max) may partially explain the lower RMR in older men, after accounting for differences in fat-free weight and fat weight. We also considered differences in energy intake and plasma thyroid hormones as possible modulators of the age-related decline in RMR in men. Three-hundred healthy men (aged 17 to 78 years) were characterized for: (1) RMR (kcal/min) from indirect calorimetry; (2) body composition from underwater weighing; (3) maximal aerobic capacity from a test of VO2max; (4) plasma thyroid hormones (total triiodothyronine [T3], free T3, total thyroxine [T4], and free T4); and (5) estimated energy intake (kcal/d) from a 3-day food diary. A curvilinear decline of RMR with age was found (P less than .01), in which no relationship was found in men less than 40 years of age (r = .10, slope = 0.002 kcal/min/yr), whereas in men older than 40 years, RMR was negatively related to age (r = -.52, slope = -0.008 kcal/min/yr). After statistical control for differences in fat-free weight and fat weight, a negative relationship between age and RMR persisted (partial r = -.30, P less than .01). It was only after control for fat-free weight, fat weight, and VO2max (partial r = -.10, P greater than .05) that no association between age and RMR was noted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640873 TI - Obese (ob/ob) mice: are they hyperoxaluric? PMID- 1640874 TI - Distribution of red blood cell velocity in capillary network, and endothelial ultrastructure, in aged rat skeletal muscle. AB - Although age-related structural and functional changes in skeletal muscle have been described extensively, little is known about the accompanying hemodynamic and structural changes in the microvasculature. The objective of this study was to use the extensor digitorum longus muscle in mid-aged (12 months) and old (28 months) Fisher 344 male rats to evaluate (1) the distribution of microvascular flow in the resting state, (2) the distribution response to a complete 30-min tourniquet ischemia, and (3) the extent of damage of capillary endothelium. Using intravital video microscopy, the mean resting velocity of red cells in capillaries was found to be 3x larger in old rats while the distribution of velocity within the microvascular bed was as heterogeneous as that in mid-aged rats. The postischemic response was characterized by the same mean peak velocity, but a slower return to velocity to the preischemic level. Within the microvascular bed, there was a less uniform postischemic response among capillaries. No long-term effect of ischemia was seen as velocity was already stable at the preischemic level 20 min after the tourniquet release. There were no differences in the pre- and postischemic densities of perfused capillaries, wet/dry weight ratios, or the occurrence of damaged capillaries. Thus, in this muscle model, aging was associated with an increased resting flow but a remarkably unaffected long-term flow response to a vasodilatory stimulus and endothelial ultrastructure. PMID- 1640875 TI - Arteriolar arcades and pressure distribution in cremaster muscle microcirculation. PMID- 1640876 TI - A simplified two-pore filtration model explains the effects of hypoproteinemia on lung and soft tissue lymph flux in awake sheep. AB - We used a simplified two-pore filtration model to examine the effects of hypoproteinemia on lung and soft tissue lymph flux in awake sheep (n = 7). To induce hypoproteinemia, we subjected each animal to 3 days of batch plasmapheresis (6 units per day). Data were collected in near steady-state conditions, 15-18 hr following completion of the last plasmapheresis episode. At this time, plasma protein concentration had fallen by 34%, while lung and soft tissue lymph protein concentrations had fallen by 55 and 62%, respectively. Lung and soft tissue lymph flows increased 52 and 87%, respectively. The plasma-to lymph osmotic pressure gradients for lung and soft tissue lymph were unchanged by protein depletion (soft tissue, 7.7 mm Hg; lung, 4.8 mm Hg). We applied these results to a heteropore model of the microvascular barrier that consisted of two types of pores: those which plasma proteins could not cross (sigma = 1) and those which proteins could cross without restriction (sigma = 0). We varied the proportion of small pores to large pores until the measured data fit a model in which the calculated microvascular hydrostatic pressures in normal and hypoproteinemic conditions were equal. This was based on the assumption that microvascular hydrostatic pressure did not change with plasma protein depletion. These conditions could be satisfied when the small pores accounted for 90% of total barrier porosity. According to the model, lymph flow increased in hypoproteinemia because of an increase in protein-free liquid flux through the large percentage of small pores; protein flux through the small percentage of large pores remained unchanged. The net result was an increase in lymph flow and a decrease in the lymph protein concentration. The model reproduced these changes even though the plasma-to-lymph osmotic pressure gradients were unchanged. We conclude that a simplified heteropore model can explain the effects of hypoproteinemia on lung and soft tissue lymph flux. PMID- 1640877 TI - Synchronous vasomotion in the human cutaneous microvasculature provides evidence for central modulation. PMID- 1640878 TI - Topographic mapping of the cutaneous microcirculation using two outputs of laser Doppler flowmetry: flux and the concentration of moving blood cells. AB - Using a "needle" probe in a template probe holder, we measured the flux and the concentration of moving red blood cell (CMBC) outputs from a Perimed (PF2B) laser Doppler instrument at 1-mm2 contiguous sites in a 8 x 8-mm area on the flexor forearm of three subjects. Using the means of the flux and CMBC recorded at each spot, a topographic contour map was constructed for each of these parameters. Viewing the two maps together, sites with four different combinations of flux and CMBC could be identified. Trephine biopsies (2 mm) of three representative sites in each subject were performed and the upper plexus was reconstructed in 3 dimensions from serial sections. High flux/high-to-medium CMBC sites were found over the spot where the ascending arterioles entered the upper plexus. Medium flux/medium-to-low CMBC sites and low flux/medium CMBC sites were found in the peripheral part of the vascular unit that was fed by the ascending arteriole. The low flux/low CMBC sites were relatively avascular zones. Video imaging of the upper plexus in the forearm showed the same overall vascular pattern as the contour maps. The highest flux and CMBC signals were recorded when horizontally oriented vessels were present in the upper third of the plexus (400-650 microns below the stratum corneum). Topographic mapping will allow one to selectively identify different microvascular areas in the skin for physiological studies. PMID- 1640879 TI - A new mounting technique for perfusion of isolated small arteries: the effects of flow and oxygen on diameter. AB - There is at present no suitable technique available for performing pressure-flow studies in isolated small arteries (i.e., less than 500 microns), in which the effects of flow and pressure on artery dimensions can be studied independently. A new mounting technique is presented in which the ends of a vessel segment are cemented to the inner surface of two cannulae, with a tip diameter slightly larger than the outer diameter of the vessel, using two-component human fibrin glue. By means of this technique the pressure drop over the cannulae can be made small. First the effect of the glue on constrictive properties is studied. The glue used has no significant influence on the norepinephrine dose-response relation or on the relaxation in response to 1.0 microM acetylcholine. Small mesenteric arteries of the rabbit with outer passive diameters (at zero pressure) of 315 microns (+/- 22 microns SEM) are studied with this method. The effects of flow (shear stress) and oxygen are investigated (vessels are preconstricted (30%) with norepinephrine (1-2 microM)). The flow range used resulted in shear stresses between 0 and 290 dyn.cm-2, a range including values found in vivo. There is a significant (P less than 0.001) decrease in diameter when flow is increased, and hypoxia (pO2 less than 30 mm Hg) augmented the preconstriction with norepinephrine (P = 0.002). The flow effect and the oxygen influence are independent of each other. These results are similar to our previous findings in the femoral artery of the rabbit (diameter about 1200 microns). PMID- 1640880 TI - Spontaneous fluctuations in oxygen tension in the cat retina. AB - Oxygen tension was recorded with double-barreled microelectrodes in the retina of anesthetized cats and monkeys. The oxygen tension (PO2) was often observed to undergo spontaneous irregular fluctuations with peak-to-peak amplitudes of about 3 to as much as 20 mm Hg. These fluctuations were observed only in the vascularized inner 40 to 50% of the retina, not in the avascular outer retina, and they were not correlated with the voltage recorded by the second barrel of the microelectrode. Oxygen records from the cat retina were subjected to Fourier analysis to determine their frequency content. The peak frequency was usually in the range of 3.5 to 10.5 c/min (0.06 to 0.18 Hz), considerably below the respiratory frequency of 20 to 30 c/min or the heart rate of 180 to 240 c/min. The power of the oxygen fluctuations fell gradually to less than 10% of the peak power by 60 c/min. It is suggested, based on the depth distribution and on comparison of these data with the literature on vasomotion, that the PO2 fluctuations are the result of changes in oxygen supply caused by normal fluctuations of arteriolar diameter (vasomotion) and/or capillary perfusion. PMID- 1640881 TI - A three-dimensional junction-pore-matrix model for capillary permeability. AB - A three-dimensional model is presented for the hydraulic conductivity and diffusive permeability of capillary endothelial clefts with a junctional strand with discrete pores and a fiber matrix in its wide parts. The model attempts to provide new insight into long-standing issues concerning the relative importance of open junction discontinuities, restricted slit regions, and matrix components in determining the permeability and selectivity of the capillary wall. The predictions drawn from the model are used to formulate new experiments to test two hypotheses concerning the molecular organization of the junction strand and the location of matrix structures in the wide part of the cleft. Using the three dimensional theoretical approach recently developed by Tsay, Weinbaum, and Pfeffer (Chem. Eng. Comm. 82, 67-102, 1989), the model first explores the behavior of three different molecular models for the junctional strand discontinuities: (i) a more frequent circular pore of 5.5-nm radius formed by isolated missing junction proteins; (ii) a restricted rectangular slit of four to eight missing proteins and 8-nm gap height; and (iii) larger more infrequent breaks of four to eight missing proteins with a gap height of 22 nm, equal to the width of the wide part of the cleft. For the circular and 8-nm gap height pores the primary molecular sieve can be located at the level of the junction strand, whereas for the 22-nm gap height pores, matrix components must be present in at least some portion of the cleft to provide the molecular filter. The water flow through the cross-bridging fibers in the wide part of the cleft is described either by a new exact three-dimensional theory (Tsay and Weinbaum, J. Fluid Mech. 226, 125-148, 1991) for an ordered periodic array or by a new approximate theory for a random array of perpendicular fibers. Both this theory and the new approximate theory for diffusion presented herein take into account for the first time the interaction between the fibers and plasmalemma boundaries. The principal predictions of the model are that (i) infrequent larger breaks are most likely required to account for small solute permeability; (ii) these larger breaks must be accompanied by a sieving matrix, but this matrix probably occupies only a small portion of the depth of the cleft and/or its entrance at the luminal surface; (iii) neither junctional pore, restricted slit, or fiber matrix models can by themselves satisfy permeability and selectivity data; and (iv) one dimensional models are a poor description of a cleft with infrequent larger breaks since the solute will be confined to small wakelike regions on the downstream side of the junction strand discontinuities and thus not fill the wide part of the cleft. PMID- 1640882 TI - Titration of immunotherapy by periodical nasal allergic challenges in the treatment of allergic rhinitis. AB - OBJECTIVE: To determine the benefits of nasal allergen challenge (NAC) in monitoring immunotherapy for allergic rhinitis in a clinical setting. DESIGN: Two hundred consecutive courses of immunotherapy, with pyridine-extracted alum precipitated allergen extracts (Allpyral), were personally carried out by the writer and analysed. Diagnosis before treatment was confirmed by NAC and the duration of treatment determined by periodical NAC. SETTING: Consultant allergist's clinical practice. PARTICIPANTS: Patients with allergic rhinitis who were referred for treatment; 79 patients were allergic to grass, 70 to the house dust mite, 30 to plantain and 21 to miscellaneous allergens. RESULTS: The mean protein nitrogen units (pnu) required to reverse an NAC was 145 467 pnu for grass, 93 771 pnu for mite, 103 137 pnu for plantain, and 121 030 pnu for miscellaneous allergen patients. The range of injections to obtain conversion to a negative NAC was wide. For grass it was 9-58 injections, for mite 6-47 injections, for plantain 4-39 injections, and for miscellaneous allergens 10-79 injections. Ten grass-sensitive patients who received an average of 477 807 pnu failed to convert to a negative NAC result. Similarly, two mite-sensitive patients who received 467 370 PNU, and one plantain-sensitive patient, one cat sensitive patient and one horse-sensitive patient, who had 389 240 pnu, 148 520 pnu and 719 540 pnu respectively, failed to convert. One patient who was very sensitive to grass pollen developed urticaria which required an injection of adrenaline. CONCLUSION: Immunotherapy for allergic rhinitis with Allpyral is effective--as determined by the conversion of NAC results from positive to negative--providing a sufficient dose is given. The manufacturer's recommended dose is inadequate. The procedure is safe for mite, plantain and miscellaneous allergens, and only one reaction occurred with grass given in a high dosage protocol, which has subsequently been altered. Considering that the British Committee of Safety of Medicines reported no deaths from Allpyral injections, its recommendations appear over cautious for this make of extract. PMID- 1640883 TI - The Papanicolaou smear histories of 237 patients with cervical cancer. AB - OBJECTIVE: This study looks at the Papanicolaou (Pap) smear histories of patients presenting with invasive cervical cancer, to assess the problems associated with the cervical cancer screening program within New South Wales. DESIGN: Prospective collection of data concerning the Pap smear history, age, menopausal status and stage of disease of patients presenting with invasive cervical cancer. SETTING: All patients with primary invasive cervical cancer referred to the Gynaecological Oncology Department of the Royal Hospital for Women, Paddington, between November 1986 and July 1990 were included in the analysis. RESULTS: Eighty-three out of 237 patients (35%) reported never having had a Pap smear taken. These patients were on average older, more frequently postmenopausal and presented with more advanced stage of disease than the rest of the population. Fifty-one patients (21.5%) stated that they had had a "normal" smear within two years. Further analysis revealed that mistaken patient recall of the date of the last Pap smear and false-negative cytological reporting were the major factors explaining these latter cases. CONCLUSION: For voluntary screening to be more effective, quality control of cytology laboratories needs to be carefully evaluated and general practitioners need to take a more active role in cancer screening. In order to reach a greater proportion of the population, a national or State cytology register should be established. PMID- 1640884 TI - The present status of psychosurgery in Australia and New Zealand. AB - OBJECTIVES: To assess the extent and nature of psychosurgery currently being performed in Australia and New Zealand, and the present status of legislation regulating its practice. METHODS: Details of current legislation were obtained through inspection of statutes and direct communication with Departments of Health. All full and associate members of the Neurosurgical Society of Australasia were surveyed by postal questionnaire. Ninety-eight neurosurgeons were surveyed, of whom 72 (73%) replied. RESULTS: In the 1980s a mean of nine (SD, 5.9) operations were performed per year; about two were performed per year in the late 1980s. Ninety per cent of these operations were performed at one centre in Sydney. The most common indications were severe and medically intractable depression and obsessive-compulsive disorder. Surgery is now exclusively stereotactic and involves the creation of lesions in the orbitomedial frontal or cingulate tracts or a combination of the two. The nature and type of surgery are comparable to those in other centres in the Western world. Regulatory legislation is in place in most, but not all, States in Australia and in New Zealand. CONCLUSIONS: Further developments of other forms of psychiatric treatments may make psychosurgery, in its present form and at its present level of validation, redundant. If it is to have a resurgence, it would have to be based on a much sounder theoretical premise, and a stronger demonstration of efficacy and predictability of effect. PMID- 1640885 TI - Longitudinal study of quality of life and psychological adjustment after cardiac transplantation. AB - OBJECTIVE: To assess the psychological adjustment and quality of life of a sample of cardiac transplant recipients over time. DESIGN: The patients were consecutive recipients of new hearts which were transplanted between November 1984 and December 1986. Thirty-eight patients were entered into the study, but at final follow-up only 27 were assessed; six patients had died and five could not be contacted. Patients were seen before transplantation, at discharge, then at 4, 8 and 12 months after transplantation and finally at a mean of 4.2 years after transplantation. They were assessed by means of standardised questionnaires. The results were compared across time and correlated with demographic data and medical data collected at the initial assessment. Only patients who were alive and responded at each point of follow-up were included in the study. SETTING: All patients were seen at St Vincent's Public Hospital and were tertiary care patients. MAIN OUTCOME MEASURES: The main outcome measures were anxiety, depression and well-being. These measures were assessed by means of the Spielberger State Trait Anxiety Scale, the Beck Depression Inventory and the Campbell Well-Being Scale. At the four year follow-up the Nottingham Health Profile was also used. RESULTS: Scores for anxiety, depression and well-being improved significantly after transplantation and did not deteriorate over time. No significant correlations were found between psychological measures and medical or demographic data. CONCLUSIONS: The results showed no evidence of mood disorder and a high level of well-being in this sample of cardiac transplant recipients up to four years after transplantation. PMID- 1640886 TI - Primary cerebral lymphoma: an association with craniopharyngioma or cadaveric growth hormone therapy? AB - OBJECTIVES: To present the first case of primary cerebral lymphoma associated with craniopharyngioma or previous cadaveric growth hormone therapy. CLINICAL FEATURES: A 22-year-old male shop assistant of European descent presented with unilateral uveitis and was found to have a high grade primary cerebral lymphoma. This occurred nine years after successful surgical resection of a craniopharyngioma without the administration of adjuvant radiotherapy. INTERVENTION AND OUTCOME: There was initial radiological resolution of cerebral lymphoma after cranial irradiation. Recurrence was noted 10 weeks later, resulting in the patient's death. CONCLUSION: The development of primary cerebral lymphoma following a craniopharyngioma is considered most likely a chance occurrence. Cadaveric growth hormone therapy may play a role in the genesis of lymphoma. PMID- 1640887 TI - A time of change in medical oncology. Problems created by the lack of coherence in Australia's health care system. PMID- 1640888 TI - Organ and tissue transplantation 1992. PMID- 1640889 TI - The teaching of multidisciplinary care. PMID- 1640890 TI - Depression in general practice. PMID- 1640891 TI - The impaired doctor. PMID- 1640892 TI - Transplantation in Australia--50 years of progress. AB - OBJECTIVE: To review the history of clinical transplantation practice in Australia. DATA SOURCES AND STUDY SELECTION: The first major source was published reports, chiefly in The Medical Journal of Australia (129 articles). The second source was personal communication with those involved in early and current transplantation programs. DATA EXTRACTION AND SYNTHESIS: The first known transplant of each organ in Australia and the results of current programs have been documented. CONCLUSIONS: Transplantation of the kidney, liver, heart, lung, pancreas, cornea, or bone marrow are available and accepted therapies for an increasing number of suitable patients, limited mainly by the number of donors. PMID- 1640893 TI - Neuropsychological functioning and sleep patterns in the elderly. AB - OBJECTIVE: To discover whether reported sleep-wake disturbances in the elderly (more frequent nocturnal awakenings, earlier waking and more day time naps) are associated with neuropsychological dysfunction. DESIGN AND SETTING: A sample of 124 residents of a retirement village complex were interviewed about their sleep patterns and given neuropsychological assessments. Reported sleep-wake difficulties were combined to form two variables, "night sleep" and "day sleep". Additional sleep variables analysed were reported sleep duration and time of wakening. Principal components analysis of the neuropsychological test scores yielded four factors: "general ability", "memory", "motor", and "cerebral efficiency". MAIN OUTCOME MEASURES: A correlation analysis was performed for sleep variables, neuropsychological factors and age, mood scale and scores on indices of participation in physical and passive activities. RESULTS: There was no correlation between "night sleep" and the factor scores derived from the neuropsychological tests. "Day sleep" was correlated with "cerebral efficiency" only. Age was correlated with the "memory" and "motor" factors, the latter also being associated with participation in physical activities. CONCLUSION: Night sleep problems are not associated with neuropsychological deficits in a non clinic population. PMID- 1640894 TI - Cost effectiveness or catch 22? PMID- 1640895 TI - Letters to the editor 1991. An audit of the MJA's correspondence columns. AB - OBJECTIVE: To evaluate correspondence published in The Medical Journal of Australia, with particular emphasis on the level of post-publication peer review which it represented. METHOD: An audit of all letters submitted to the Journal for publication in 1991. RESULTS: Six hundred and forty-eight letters were received; 506 (78%) were published and 142 (22%) were not. Three hundred and twenty-nine of the published letters were written in response to material published in the Journal: 96 of these were related to other letters, 71 were replies to other letters by authors, 43 related to original articles, 42 to leading articles and 77 to other articles. Approximately 20% of all original articles published in the Journal attracted correspondence which was published. The commonest reasons for writing were concern about possible flaws in the design of a study, to add information of interest to the subject or to criticise the conclusions reached in the study. CONCLUSIONS: Readers are perhaps not taking full advantage of the opportunity for post-publication peer review provided by correspondence columns in the MJA. PMID- 1640896 TI - Rhabdomyolysis due to redback spider envenomation. PMID- 1640897 TI - Emergency transport of critically ill children. PMID- 1640898 TI - Doctors' advice to pregnant women regarding alcohol and tobacco consumption. PMID- 1640899 TI - Heart attacks and the Newcastle earthquake. PMID- 1640900 TI - Pesticides and other chemicals in cigarette tobacco. PMID- 1640901 TI - Cholera in Adelaide. PMID- 1640902 TI - Autopsy rates. PMID- 1640903 TI - Low risk of HIV-1 infection from blood donation: a test-based estimate. PMID- 1640904 TI - High dose nifedipine and fludrocortisone for intractable hiccups. PMID- 1640905 TI - Pap smear reminder systems. PMID- 1640906 TI - Combined ciprofloxacin/rifampicin therapy in methicillin-resistant Staphylococcus aureus (MRSA) infection. PMID- 1640907 TI - Convulsive syncope and the diagnosis of a first epileptic seizure. PMID- 1640908 TI - Adjuvant therapy for breast cancer. PMID- 1640910 TI - International Society of Pediatric Oncology, SIOP XXIV Meeting. Hannover, Federal Republic of Germany, October 12-16, 1992. Abstracts. PMID- 1640909 TI - Allergic rhinitis and immunotherapy. PMID- 1640911 TI - [Carious pathology in selective IgA deficit]. AB - The relationship between levels of secretory IgA and incidence of dental caries has been the object of controversial studies. Selective IgA deficiency (SIgAD) is the commonest primary immunodeficiency and may be found in apparently healthy individuals but is also associated with a variety of diseases. In the present study the authors evaluated the prevalence [correction of incidence] of caries by means of caries indexes in a group of children with severe and partial SIgAD and in a group of children age-matched healthy control. Evaluated caries indexes were significantly higher in children with severe SIgAD as compared to control groups. PMID- 1640912 TI - [Lymphocyte subpopulations in inflammatory periapical lesions. A histopathological and immunohistochemical study in 10 cases]. AB - The authors, thanks to the application of monoclonal antibodies, as well as the immunohistochemical technique of APAAP, have traced the qualitative and quantitative features of inflammatory cells implied in periapical lesions. Moreover ten patients, of whom 6 males and 4 females aged between 20 and 60 have been tested. The immunohistochemical reactions revealed a heterogeneous population of B and T (T4-T8) lymphocytes, together with myeloid trunk cells (granulocytes and histiocytes). The B lymphocytes form nearly 31.5% of all the inflammatory cell, whereas the T types form about 55.8. The granulo-histiocyte part implies 11.1% of all the inflammatory cells themselves. The average percentages of the roted inflammatory cells have been compared with two diagnostic categories of periapical granuloma and periapical cyst. However, by comparing the obtained results with the ones described by other authors, we notice agreement as for as qualitative analysis is concerned, while as for quantitative analysis, some differences are proved. Finally, this situation shows that the quantitative demonstration of inflammatory cell populations is only a moment in the development of immune reactions in the inflammatory tissue. PMID- 1640913 TI - [The importance of direct immunofluorescence in the diagnosis of oral lichen planus. A clinical study and proposal of new diagnostic criteria]. AB - A series of 40 lesions of various kinds as lichen planus are examined using samples stained with trichromic test. HLA-DR expression with immunoperoxidase technique and direct immunofluorescence using the standard techniques. The aim of the study was to discover the usefulness for diagnosis of direct immunofluorescence, above all in histologically uncertain cases. The results suggest the view that direct immunofluorescence is essential for diagnosis of Lichen planus, in all clinical aspects. The author concludes with description of clinical proceeding for differential diagnosis between withe and erosive lesions of mouth. PMID- 1640914 TI - [Celiac disease and recurrent aphthous stomatitis. The clinical and immunogenetic aspects]. AB - The frequency of HLA class II (DR and DQ) antigens is analyzed in 113 subjects affected by coeliac disease, nineteen of them suffering from recurrent aphthous stomatitis. A significant association was found between DRw10 and DQw1 HLA antigens and the two diseases in the 19 subjects suffering from both diseases. PMID- 1640915 TI - [Hemimandibular reconstruction via an autologous transplant of vascularized fibula. A report of a clinical case]. AB - The authors illustrate the advantage of vascularised as opposed to conventional edges in the reconstruction of the jaw, focusing in particular on the use of a fibular autologous transplant. After a rapid description of the surgical technique used to remove the graft, they report a case of mandibular reconstruction in a young patient who had been involved in a shooting accident which had led to the loss of the left of this jaw. PMID- 1640916 TI - [Cervical trauma in the pathogenesis of cranio-cervico-mandibular dysfunctions]. AB - A sudden cervical extension-flexion (whiplash) can cause a temporomandibular pathology with a direct and indirect mechanism of action. A total of 24 patients of both sexes who had undergone acute cervical trauma, which had led to masticatory dysfunction of a meniscal or algomyo-facial type, were examined. The most frequent signs and symptoms were regional pain, a qualitative and quantitative change in movements, cephalea, and articular noise. A complete condylo-meniscal block was observed in three cases. Concomitant radiographic tests using a trans-cranial projection confirmed clinical findings. A multidisciplinary individual therapeutic approach ensured complete functional recovery; prognosis varied with regard to cephalalgia which is related to the individual's psycho-behavioural substrate. The paper stresses the importance of early diagnosis and targeted treatment in order to prevent symptoms from becoming chronic thus making the disorder a disability which is difficult to treat. PMID- 1640917 TI - [A rare case of fibrous dysplasia in an elderly patient. The surgical intervention and prosthetic rehabilitation]. AB - The authors report a rare case of fibrous dysplasia of the upper jaw bone in an elderly patient. Diagnostic iter, surgical therapy and rehabilitation are reported. PMID- 1640918 TI - [A clinical evaluation of the outcome of a bone graft from the iliac crest]. AB - The paper examine 40 cases of bone graft from the iliac crest used in maxillo facial surgery. The immediate and late complications included pain with resulting difficulty of walking and, less frequently, hematoma, sensitivity disorders and dehiscence of the wound. Late complications were most frequently related to esthetic problems as well as a negligible number of persistent cases of difficult walking and neurological deficiencies. The results obtained were comparable to those most recently reported in the literature. The low incidence of immediate and late sequelae at the donor site and the characteristics of the bone graft confirm the suitability of iliac crest bone graft, in particular for use in reconstructive maxillo-facial surgery. PMID- 1640919 TI - [Condylar osteosynthesis after Krenkel's technic. The authors' personal experience]. AB - The paper illustrates the authors' use of surgery to treat condylar fractures using Krenkel's technique which entails a cutaneous incision under the mandibular corner and the application of a clip screw in relation to the longitudinal axis of the upright branch of the jaw. This surgical technique, which is above all indicated in cases of low subcondylar fractures, provides a rigid internal fixation of the fracture stumps, thus preventing intermaxillary lock. Several stages in the operation are described in dental and the intrinsic advantages of this method are then outlined together with the results obtained. PMID- 1640920 TI - National action plan to combat multidrug-resistant tuberculosis. AB - At no time in recent history has tuberculosis (TB) been as great a concern as it is today. TB cases are on the increase, and the most serious aspect of the problem is the recent occurrence of outbreaks of multidrug-resistant (MDR) TB, which pose an urgent public health problem and require rapid intervention. A Task Force composed of representatives of many federal agencies has developed a National Action Plan for addressing this problem. The Task Force identified a number of objectives to be met if MDR-TB is to be successfully combatted. These objectives fall under the categories of a) surveillance and epidemiology- determining the magnitude and nature of the problem; b) laboratory diagnosis- improving the rapidity, sensitivity, and reliability of diagnostic methods for MDR-TB; c) patient management--effectively managing patients who have MDR-TB and preventing patients with drug-susceptible TB from developing drug-resistant disease; d) screening and preventive therapy--identifying persons who are infected with or at risk of developing MDR-TB and preventing them from developing clinically active TB; e) infection control--minimizing the risk of transmission of MDR-TB to patients, workers, and others in institutional settings; f) outbreak control; g) program evaluation--ensuring that TB programs are effective in managing patients and preventing MDR-TB; h) information dissemination/training and education; and i) research to provide new, more effective tools with which to combat MDR-TB. The Action Plan lays out a series of activities to be undertaken at the national level. For each category, the Plan presents statements of problems to be overcome, followed by a summary of the objective to be achieved and steps to be carried out. For each implementation step, responsibility is assigned to the appropriate organization and start-up dates are listed. PMID- 1640921 TI - Management of persons exposed to multidrug-resistant tuberculosis. AB - Recent outbreaks of multidrug-resistant tuberculosis (MDR-TB) have posed challenges for the management of exposed persons. This report offers suggestions for evaluating and managing persons (i.e., contacts) who have been exposed to patients with infectious MDR-TB (TB due to strains of Mycobacterium tuberculosis resistant to both isoniazid [INH] and rifampin [RIF]), provides background information on alternative preventive therapy regimens with drugs other than INH or RIF, and presents considerations relevant to making a decision to offer one of these alternative regimens. PMID- 1640922 TI - Counseling practices of primary-care physicians--North Carolina, 1991. AB - Because 80% of the U.S. population visits a physician each year (1), physicians are an important source for health education. In particular, physicians have unique opportunities to influence and modify health-risk behaviors of their patients. During 1991, the North Carolina Department of Environment, Health, and Natural Resources (DEHNR), the University of North Carolina at Chapel Hill, and CDC conducted a survey of nonmilitary primary-care physicians practicing in North Carolina regarding counseling and referral practices. This report summarizes results of this survey, including estimates of the proportion of primary-care physicians who counsel and/or refer for treatment patients who smoke, abuse drugs or alcohol, or have diet- or nutrition-related problems. PMID- 1640923 TI - Surgical sterilization among women and use of condoms--Baltimore, 1989-1990. AB - Since 1980, surgical sterilization among women has become the most common contraceptive method used among women aged greater than 30 years in the United States and is used by 28% of women aged 15-44 years. A previous report of women in drug treatment suggested that women who have been surgically sterilized were less likely to report condom use--an effective measure for prevention of human immunodeficiency virus (HIV) infection and sexually transmitted diseases (STDs)- than were nonsterilized women. This report summarizes a study of the relation between surgical sterilization, risk status for STDs and HIV, and use of condoms among women who reside in two inner-city, minority neighborhoods in Baltimore. PMID- 1640924 TI - Patient exposures to HIV during nuclear medicine procedures. AB - Although the potential for transmission of bloodborne pathogens to patients through transfusion of contaminated blood is well known, it is less widely recognized that such transmission can also occur during medical procedures involving withdrawal and reinjection of blood or blood products (e.g., nuclear medicine procedures). Since 1989, three patients (two in hospitals in the United States and one in the Netherlands) undergoing nuclear medicine procedures have been reported to have inadvertently received intravenous injections of blood or other material from patients infected with human immunodeficiency virus (HIV). Two of these patients are known to have become infected with HIV during these procedures; HIV test results are not available for the third patient. This report summarizes these three incidents and provides recommendations for preventive measures. PMID- 1640925 TI - Testing for HIV in the public and private sectors--Oregon, 1988-1991. AB - Counseling and testing persons for human immunodeficiency virus (HIV) infection is a key component of the public health strategy for reducing transmission of HIV in the United States (1,2). In 1991, the federal government allocated $100 million to state and local health agencies to provide counseling and testing programs in public clinics for at-risk persons, including persons who may not otherwise use public health services. However, the relative contribution of HIV testing in public clinics to HIV testing in the private sector is unknown. To compare HIV testing in Oregon public clinics to overall HIV testing, the Health Division (HD) of the Oregon Department of Human Resources, in cooperation with CDC, reviewed data collected from September 1, 1988, through August 31, 1991, on public and private HIV testing in Oregon. This report summarizes findings for HIV testing rates and assesses the importance of publicly funded testing in identifying HIV-seropositive persons. PMID- 1640926 TI - Misclassification of infant deaths--Alaska, 1990-1991. AB - In June 1991, the Alaska Section of Vital Statistics reported that nine deaths of Alaskan Native infants occurred in seven villages in southwestern Alaska from January 1990 through June 1991. In comparison, seven Alaskan Native infant deaths occurred in these villages during 1986-1989. Two of the deaths during 1990-1991 had been attributed to acute viral myocarditis (International Classification of Diseases, Ninth Revision [ICD-9], code 422.9) and three to viral or unspecified pneumonitis (ICD-9 codes 480.9 and 486), while from 1985 through 1989, one infant death in these villages had been attributed to either of these causes. An examination of the clinical histories of these nine infants by the Alaska Division of Public Health (ADPH) suggested some of the diagnoses might be inaccurate. This report summarizes an investigation by the ADPH to assess the accuracy of the immediate cause of death recorded on the death certificates for the nine infants. PMID- 1640927 TI - Ectopic pregnancy--United States, 1988-1989. AB - Although the number and rate of ectopic pregnancies in the United States increased from 1970 through 1987, they stabilized from 1987 through 1989 (1). This report presents data regarding the number and rate of ectopic pregnancies and ectopic pregnancy-related deaths in the United States from 1988 through 1989 and compares those data with information reported since 1970. PMID- 1640928 TI - Effect of prolonged treatment with propionyl-L-carnitine on erucic acid-induced myocardial dysfunction in rats. AB - The aim of this study was to evaluate the ability of propionyl-L-carnitine to prevent cardiac damage induced by erucic acid. Rats were fed for 10 days with normal or 10% erucic acid-enriched diets with or without propionyl-L-carnitine intraperitoneally injected, (1 mM/kg daily, for 10 days). The erucic acid diet produced increases in triglycerides (from 5.6 to 12.4 mg/gww, P less than 0.01), and free fatty acids (from 2.0 to 5.1 mg/gww, P less than 0.01), but no changes in phospholipids. When the hearts were perfused aerobically with an isovolumic preparation there was no difference in mechanical activity. On the contrary, when pressure-volume curves were determined, the pressure developed by hearts from the erucic acid-treated rats were reduced. Independent of diet, propionyl-L-carnitine treatment always produced positive inotropy. This was concomitant with improved mitochondrial respiration (RCI 5.1 vs 9.3, P less than 0.01), higher tissue ATP content (10.3 vs 18.4 mumol/gdw P less than 0.01) and reduction of triglycerides (12.4 vs 8.0 mg/gww, P less than 0.01). These data suggest that propionyl-L carnitine, when given chronically, is able to prevent erucic acid-induced cardiotoxicity, probably by reducing triglyceride accumulation and improving energy metabolism. PMID- 1640929 TI - Characteristic induction of 70,000 da-heat shock protein and metallothionein by zinc in HeLa cells. AB - The synthesis of a 70,000 dalton-heat shock protein (hsp70) is one of several heat shock proteins induced in HeLa cells during the incubation in medium containing zinc sulphate. The synthesis of hsp70 was increased in the presence of 200 microM zinc sulphate and above, but not at 100 microM zinc sulphate. On the other hand, the synthesis of metallothionein was activated in the presence of 100 microM zinc sulphate and above. Uptake of zinc into the cells depended on the concentration of zinc sulphate in the medium. The separation of intracellular zinc into three fractions by gel filtration chromatography; high molecular, metallothionein, and low molecular fractions, showed that zinc in the low molecular weight and metallothionein fractions was elevated in the presence of 100 microM zinc sulphate in the medium, whereas increase in the zinc content of the high molecular weight fraction occurred at 200 microM zinc sulphate and above. Inhibition of cell growth and cellular protein synthesis was also observed at 200 microM zinc sulphate and above, but not at 100 microM. From these findings, since the induction of hsp70 synthesis and inhibition of cell growth occurred concomitantly with the increase of zinc in the high and low molecular weight fractions, hsp70 seemed not to function in the detoxification of zinc, but it may participate in the repair of zinc-induced damage. PMID- 1640930 TI - Characterization of gastrin binding to colonic mucosal membranes of guinea pigs. AB - Gastrin has significant growth and metabolic effects on colonic mucosal cells. It is, however, not known if gastrin receptors are present on colonic mucosal cells that may directly mediate the reported biological effects of gastrin. In the present studies, the presence of specific gastrin binding sites on colonic mucosal membranes was investigated and the binding sites were further characterized. Crude membranes from colonic mucosa of guinea pigs were analyzed for specific binding to gastrin by our published procedures. A significant number (14.7 +/- 1.8 fmoles/mg protein) of high affinity gastrin binding sites (Kd = 0.49 +/- 0.05 mM) were measured, that were specific for binding gastrin/CCK related peptides and demonstrated negligible binding affinity for all other unrelated peptides examined. In addition a large number of low-affinity (Kd = approximately 1 microM) binding sites were present. In order to further characterize the molecular size of gastrin binding proteins, we used the chemical cross-linking methods, and observed at least four bands of gastrin binding proteins (GBPs) (approximately 33, 45, 80 and 250 KDa), both under reducing and non-reducing conditions, indicating that these proteins were not sub-units of forms linked by disulfide bonds. Interestingly, majority of the specific gastrin binding sites (approximately 70%) were present on the 45 KDa protein, unlike other target cells of gastrin. The presence of N- and O-linked glycosylated moieties were indicated on the 45 KDa protein, based on enzymatic de glycosylation studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1640931 TI - Tyrosinated, detyrosinated and acetylated tubulin isotypes in rat brain membranes. Their proportions in comparison with those in cytosol. AB - The heterogeneity of alpha-tubulin and the relative proportions of the tubulin isotypes were investigated in brain membranes of rats of 1, 25 and 180 days of age by using four anti-alpha-tubulin antibodies: a) the monoclonal DM1A antibody, specific for alpha-tubulin; b) the monoclonal 6-11B-1 antibody, specific for acetylated tubulin; c) a polyclonal antibody (Glu antibody), specific for detyrosinated tubulin; and d) a polyclonal antibody (Tyr antibody), specific for tyrosinated tubulin. We found that rat brain membranes contain the three tubulin isotypes mentioned above. The proportions of tyrosinated and detyrosinated tubulin relative to total alpha-tubulin were somewhat lower in membrane than in cytosol in animals of 25 and 180 days of age. At day one of development, the proportions in membrane were similar to those found in cytosol. With respect to the acetylated form, it was about 20 times higher in membrane than in cytosol at the three ages studied. The proportion of acetylated tubulin was determined in different subcellular fractions: myelin, synaptic vesicles, mitochondria, microsomes, and plasma membrane. While the amount of total tubulin differed between the different subcellular fractions, the proportion of acetylated tubulin relative to total alpha-tubulin was constant and similar to that found in total membranes. The proportion of acetylated tubulin was also investigated in non neural tissues (kidney, liver and lung). Although values for cytosol were about 10-fold higher than that found in brain cytosol, no detectable values for membranes could be obtained in these organs. PMID- 1640932 TI - Design of liposome to improve encapsulation efficiency of gelonin and its effect on immunoreactivity and ribosome inactivating property. AB - Gelonin, purified from the seeds of Gelonium multiflorum, using cation-exchange and gel-filtration chromatography was characterised for its purity, homogeneity and molecular weight by reverse-phase HPLC (RP-HPLC) and SDS-PAGE analysis. The HPLC purified gelonin was used for entrapment studies in the liposomes. Liposomes were prepared by reverse phase evaporation (REV) technique using three different types of lipid composition in the same molar ratio. The method resulted in 75-80% entrapment efficiency of gelonin in the liposomes. Entrapped and unentrapped gelonin was characterized for physico-chemical, immunochemical and biological properties. The immunoreactivity of entrapped gelonin was fully preserved but the ribosome-inactivating property was slightly inhibited. The method involved mild conditions, highly reproducible and the liposomes produced appeared to be stable for several months. It has important implications in the development of cell type specific cytotoxic agents where a chemical cross-linking is involved which significantly inhibits both immunoreactivity and ribosome-inactivating ability of the toxin. PMID- 1640934 TI - Role of the rat liver in the disposal of a glucose gavage. AB - An oral gavage of either 3, 1, or 0.1 mmoles of glucose was given to rats under standard feeding conditions or food deprived for 24 hr. The blood flow of the portal and suprahepatic veins as well as the hepatic balances for glucose, lactate, alanine and pyruvate were estimated. In fed rats, after the administration of an oral 3 mmoles load, the liver actually released 310 mumoles of glucose and 90 of lactate, amounts that could be accounted for by the uptake of alanine (148 mumoles) and small loss of glycogen (275 mumoles of glycosyl residues). In starved rats, however, the liver took a very high proportion (c. 71%) of the glucose absorbed, both as glucose (780 mumoles), lactate and pyruvate (892 mumoles) or alanine (134 mumoles). The synthesis of glycogen was considerably limited, accounting for only 205 mumoles, and leaving practically one mmol of glucose equivalent energy available for liver function and the synthesis of other compounds. Practically all glycogen was synthesized directly from glucose, since the synthesis from 3 C carriers was less than a 5%. Smaller gavages (1 or 0.1 mmoles) resulted in a much lower liver uptake activity. The strikingly different activity of the liver with respect to the available glucose and 3 C fragments could not be explained alone by the circulating levels of these compounds, suggesting a very deep influence of the intestine in hepatic function. The liver plays a very passive role in fed animals, with a very small involvement in the disposal of a glucose load, whereas it takes on an important role when the overall availability of energy is diminished. PMID- 1640933 TI - Relevance of glutamine metabolism to tumor cell growth. PMID- 1640935 TI - Intestinal handling of a glucose gavage by the rat. AB - An oral gavage of either 3, 1 or 0.1 mmoles of 14C-labelled glucose was given to rats under standard feeding conditions or food deprived for 24 hr. The fate of the glucose label was determined at 10, 15, 30 and 60 min after gavage; at 60 min 40% of the glucose was absorbed in fed rats (60% in food deprived). The portal vein blood flows were determined and the levels of glucose, lactate, alanine and pyruvate, and their radioactivity, as well as that of CO2 were measured in both portal and arterial blood. The net computed glucose and 3-carbon carriers (lactate, alanine and pyruvate) actually released into the portal system by the intestine was lower than the amount of glucose taken up from the intestinal lumen in one hour. Oxidation to 14CO2 accounted for a 12-15% of the absorbed glucose. The size of the gavage deeply affected the proportion of glucose released into the portal blood (c. 50% with a 3 mmoles gavage and practically nil with a 0.1 mmoles gavage), but it affected much less the generation of lactate and other 3 C carriers. In fed rats, the net intestinal balance of non-radioactive glucose was negative, and that of lactate positive; when radioactive glucose was considered, the pattern was inverted. In starved rats, both glucose and lactate were released in large proportions by the intestine, but alanine efflux was lower. It can be concluded that the intestine consumes a considerable proportion of glucose in the fed state. Glucose handling by the intestine is compartmentalized in two functional circuits: glucose is taken up from the arterial blood and used for intestinal metabolism and lactate production, luminal glucose is absorbed mainly unaltered and transferred to the portal blood. Thus, the generation of lactate is mainly related to the availability of arterial glucose. In addition to the release of the ingested glucose as 3 C carriers or glucose, an extraportal pathway for glucose transfer into the bloodstream is postulated. PMID- 1640936 TI - High affinity DNA-microtubule associated protein interaction. AB - We have isolated the MAP/tau proteins from twice-cycled chick brain microtubule preparations and demonstrated that they are responsible for the nitrocellulose DNA binding activity we and others have measured. Using the isolated MAP/tau proteins we then measured the apparent affinity constant K(app) for the homologous chick DNA interaction and found evidence for two equilibrium affinity classes-a K(app) = 6 x 10(7) M-1, responsible for the bulk of the DNA binding activity and a small (less than 10%) higher affinity K(app) = 10(8) - 10(9) M-1, likely due to sequence specific binding protein species. Using the same chick brain MAP-tau protein, a heterologous interaction with D. melanogaster DNA, was found to possess just the lower affinity class-K(app) = 2 x 10(7) M-1. Under stringent binding conditions we carried out equilibrium nitrocellulose filter binding experiments in a ternary reaction mixture at constant MAP/tau protein and 35S radiolabelled chick DNA concentration using increasing and excess concentrations of competitor DNAs of different sources. The order of competitor strengths found was-chick DNA greater than mouse DNA greater than D. melanogaster = E. coli. DNA. These data and specifically the homologous DNA: protein case being the strongest competitor corroborate our previous studies using total microtubule protein and provide new evidence for a conserved interaction of a small DNA sequence class with MAP/tau protein species. Moreover, these data allow us to conclude that the conserved DNA sequence: MAP/tau protein interactions do not critically depend upon any energetic feature co-involving tubulin for their properties since tubulin is absent from these preparations. PMID- 1640937 TI - Effect of calcium-binding protein regucalcin on Ca2+ transport system in rat liver nuclei: stimulation of Ca2+ release. AB - The effect of regucalcin, a calcium-binding protein isolated from rat liver cytosol, on Ca2+ transport in rat liver nuclei was investigated. Ca2+ uptake and release were determined with a Ca2+ electrode. Ca2+ uptake increased dependent on adenosine triphosphate (ATP; 0.5-2.0 mM), while the uptake was negligible in the presence of 2 mM ADP or AMP. Regucalcin (0.5-2.0 microM) had no effect on Ca2+ uptake following addition of 2.0 mM ATP. Meanwhile, Ca2+, which accumulated in the nuclei during 10 min after ATP addition, was significantly released by the addition of regucalcin. This release was dose-dependent (0.1-2.0 microM). Vanadate (100 microM) and guanosine triphosphate (100 microM) did not cause a significant release of Ca2+ from the nuclei. Trifluoroperazine (TFP; 50 microM), an antagonist of calmodulin, significantly increased Ca2+ release from the nuclei. The presence of regucalcin (0.5 microM) further enhanced the TFP effect. These results indicate that regucalcin stimulates Ca2+ release from liver nuclei, and that the effect is not influenced by calmodulin antagonist. The finding suggests that regucalcin can regulate the Ca2+ transport system in rat liver nuclei. PMID- 1640938 TI - Decrease of myocardial infarct size with desferrioxamine: possible role of oxygen free radicals in its ameliorative effect. AB - The ability of an iron chelator, desferrioxamine, to inhibit the infarct size in in vivo rat heart was assessed. Anaesthetised rats were subjected to coronary artery ligation (CAL) for 72 hr and infarct size was measured macroscopically using TTC staining. Systolic blood pressure and ECG were monitored. Desferrioxamine (10 mg/kg and 20 mg/kg i.v.) administered half an hour after CAL markedly reduced the infarct size. However, drug treatment did not alter the systolic blood pressure of animals. In addition, desferrioxamine in vitro and in vivo demonstrated an inhibition of rat PMN-evoked and luminol-enhanced chemiluminescence. The capacity of desferrioxamine to impair the generation or to scavenge directly oxygen free radicals may be responsible for its beneficial effect on myocardial infarct size in rats. PMID- 1640939 TI - Demonstration of multiple forms of bovine brain myristoyl CoA:protein N-myristoyl transferase. AB - Four distinct N-myristoyl transferase (NMT) activity peaks, designated I, II, III, and IV, were separated from the cytosolic fraction of bovine brain by DEAE Sepharose column chromatography. Peaks I, II, III and IV were characterised biochemically with respect to substrate specificity: with cAMP-dependent protein kinase and pp60src derived peptides, and by their apparent molecular mass. The apparent molecular mass of peaks I, II, III and IV were 190 kDa, 224 kDa, 390 kDa and 76 kDa, respectively. These results indicate that bovine brain contains multiple forms of NMT. PMID- 1640940 TI - [Diagnosis and therapy of anemia in childhood. Part 2. Hemolytic anemia and anemia in the newborn infant]. PMID- 1640941 TI - [Diseases involving the heart and kidney in children and adults]. AB - An association of renal and cardiac manifestations can be observed in a variety of diseases. The pathogenetic factors may include, firstly, a disturbance of organ development due to chromosomal aberration or an underlying syndrome or, secondly, infectious, immunologic and metabolic factors. In addition, primarily isolated diseases of the heart or the kidney may lead to damage of the previously unaffected organ. The present article gives a review on renal diseases associated with heart diseases in children and adults. PMID- 1640942 TI - [How do parents adjust to a child with cancer? A clinical study of the psychosocial status of parents of children with cancer]. AB - As chronic life-threatening diseases, cancer or leukemia in children generates an extreme situation for the family involved that can go on for years. Psychosocial care for all family members by a pediatric oncologist should be integrated into the treatment plan, as this is both helpful and necessary. PMID- 1640943 TI - [Farquhar disease. Reduced phagocyte function in a 9-year-old girl with erythrophagocytic lymphohistiocytosis]. AB - We report phagocyte function tests in a female infant with familial hemophagozytotic lymphohistiocytosis. Chemiluminescence and killing of Saccharomyces cerevisiae by monocytes and granulocytes before chemotherapy and in remission were examined. Patients' monocytes and granulocytes showed a markedly reduced chemiluminescence and killing capacity irrespective of the stage of disease. PMID- 1640944 TI - [Killian-Teschler-Nicola syndrome (Pallister-Killian syndrome, mosaic tetrasomy 12p)]. PMID- 1640945 TI - [Townes-Brocks syndrome. Case report and review of the literature]. AB - We report on a 14 months old Turkish girl with bilateral triphalangeal thumb and preaxial hexadaktyly on her left hand, bilaterally missing third toes and "Satyr ears" as typical features of Townes-Brocks Syndrome. Besides reviewing all previous publications we discuss frequency and significance of all features- especially of anorectal malformations and the third missing toe. PMID- 1640946 TI - [Anomalous origin of the left coronary artery from the pulmonary artery. Variability of clinical aspects, echocardiography and angiography findings]. AB - OBJECTIVES: Analysis of symptoms, diagnostical difficulties and follow-up in infants and children with anomalous origin of the left coronary artery from the pulmonary artery. METHODS: Retrospective study; 12 children between 3 weeks and 2 years old; time period: 1980-1991. RESULTS: Three infants were detected on routine examination because of a new cardiac murmur, the others presented with signs of cardiac failure. Cross sectional echocardiography and color Doppler flow mapping allowed to verify the suspected diagnosis. However, in one infant a false negative cross sectional echocardiographic result was obtained. In this case nuclear magnetic resonance imaging was able to delineate the exact anatomy. Mean preoperative left ventricular ejection fraction: 33 +/- 4%; percentage of infants below the age of 6 months: 92%; surgery related mortality: 66%; mean follow-up of the remaining 4 patients being in good clinical condition: 2.9 +/- 1 years. CONCLUSIONS: 1. An anomalous origin of the left coronary artery should be included into the differential diagnosis when a new cardiac murmur is detected. 2. Possibility of false-negative echocardiographic results is emphasized. 3. With early symptoms and highly reduced left ventricular function, the mortality is still high. PMID- 1640947 TI - [Detection of drugs in meconium]. AB - BACKGROUND: The number of newborn infants exposed to drugs in utero is on the increase in many European countries. As drug use reported by addicted pregnant women is unreliable there is a need for an accurate test to determine the drugs to which an infant has been exposed in utero. The purpose of this study was to evaluate the reliability of toxicology testing in meconium compared with traditional urine testing. METHODS: From twenty newborn infants born to drug dependent mothers, meconium and urine were collected as soon as possible after birth and tested for drugs with the same radioimmunoassay. Five neonates were premature (Gestational weeks less than 37), six were small and three microcephalic for gestational age. RESULTS: Meconium was positive for drugs in 19 infants (95%) (Methadone 9, Morphine 9, Cocaine 6, Cannabis 4). Urine testing revealed the presence of drugs in 13 babies (65%) (Methadone 9, Morphine 6, Cocaine 4, Cannabis 1, Barbiturates 1). Five infants did not have any drug withdrawal, five had mild and ten severe withdrawal symptoms necessitating treatment with chlorpromazine and in four instances additional pethidine. CONCLUSIONS: Meconium is not only easier to collect but also at least as reliable as urine for drug detection in neonates. PMID- 1640948 TI - [Idiopathic hydrocephalus in adolescence]. AB - BACKGROUND: Decompensation of chronic idiopathic hydrocephalus can occur at every age, but seems to be rather frequent in the middle of the second decade. From this observation, the question arises, whether or not in these cases a special manifestation of hydrocephalus occurs and, should the situation arise, whether this finding might influence the discussion about pathogenesis. METHODS: We give some casuistic material about six hydrocephalic patients who became symptomatic between their 12th and 16th year of life. RESULTS: All of these patients showed a tri-ventricular appearance of hydrocephalus as well as radiological signs of chronicly elevated intracranial pressure, while clinical signs and symptoms differed considerably. These findings are linked to the discussion of the pathogenesis of so-called aqueductal stenosis. CONCLUSIONS: Whenever, after normal development in childhood, symptoms like increasing headache, poor concentration, dizziness or disturbances of gait appear during puberty, X-ray diagnosis of the skull is recommended. If it shows the signs of chronic elevated intracranial pressure, further investigations are necessary. PMID- 1640949 TI - [Environmental chemoprevention of Haemophilus influenzae type B meningitis. Consequences of 2 indirectly related case pairs]. AB - BACKGROUND: Within a few months we twice observed the following situation: In each of two different communities, a young child fell ill with meningitis caused by Haemophilus influenzae type B (HIB). One week later, a second case occurred in the same community. Both patients had had no direct contact with each other. But each had an asymptomatic older sibling. These siblings attended the same kindergarten and had close contact with each other. The isolated HIB strains were identical (capsular type b, biotype I, outer membrane protein subtype 1 and lipopolysaccharide serotype 1) and were beta-lactamase-negative. CONCLUSION: Since it must be assumed that the causative HIB strains circulated in the respective kindergartens and were transmitted to the patients by their healthy siblings, a rifampicin chemoprophylaxis was instituted which included all kindergarten children and their younger siblings. Since the current guidelines on chemoprophylaxis in HIB meningitis do not deal with a situation like the one encountered by us, a revision of the present guidelines was proposed and has been implemented in the meantime. PMID- 1640950 TI - [Perinatal hepatitis B virus transmission]. AB - Using the highly sensitive Polymerase chain reaction (PCR) hepatitis B virus (HBV) DNA has already been detected in many patients negative for all other serological HBV markers [12]. But yet, the relevance of these findings as a marker of infectivity has not been determined. We therefore have used the PCR to examine the perinatal route of HBV transmission by testing sera from 109 mother child pairs in Yaounde, Cameroon. HBV-DNA was detected in 25 (23%) of the mother's sera from which only 5 were positive for HBsAg. At the age of 6 months only one baby out of 25 who could be retested had become positive for HBV-DNA, HBsAg, and HBeAg. Low serum HBV-DNA levels which are still detectable by the PCR therefore seem not to be associated with a high risk of perinatal HBV transmission. PMID- 1640951 TI - [Dioxins, furans and breast milk. Report of the Commission of Environmental Concerns of the Academy of Pediatrics and Adolescent Medicine and the Nutrition Commission of the German Society of Pediatrics]. PMID- 1640952 TI - A randomized comparison of transcervical and transabdominal chorionic-villus sampling. The U.S. National Institute of Child Health and Human Development Chorionic-Villus Sampling and Amniocentesis Study Group. AB - BACKGROUND: Chorionic-villus sampling is done in early pregnancy to obtain fetal cells for the prenatal diagnosis of genetic and chromosomal defects. Transcervical chorionic-villus sampling has been shown to be safe and effective in national trials. Recently, an alternative transabdominal technique has been suggested as potentially easier and safer. METHODS: From April 1987 through September 1989, we prospectively compared transcervical and transabdominal chorionic-villus sampling in 3999 women with singleton pregnancies in whom the risk of a genetically abnormal fetus was increased. Women between 7 and 12 weeks of gestation underwent ultrasonographic evaluation of placental and uterine position. Those with active vaginal infections, active bleeding, or cervical polyps were excluded. If the obstetrician thought either sampling procedure was acceptable, the woman was asked to consent to random assignment to one of the two procedures. Both groups were followed to determine the outcome of pregnancy and the rate of spontaneous fetal loss after chorionic-villus sampling. RESULTS: Among the 3999 women who entered the study, sampling was attempted in 3873 (97 percent), 1944 of whom had been assigned to undergo transcervical sampling and 1929 to undergo transabdominal sampling. Of these 3873 women, sampling was eventually successful in 3863. Sampling was successful after a single insertion of the sampling instrument in 94 percent of the transabdominal procedures and 90 percent of the transcervical procedures. Among the women with cytogenetically normal pregnancies who had sampling because of maternal age, the rate of spontaneous fetal loss through 28 weeks of pregnancy was 2.5 percent in the transcervical-sampling group and 2.3 percent in the transabdominal-sampling group (difference, 0.26 percent; 95 percent confidence interval, -0.5 to 1.0 percent). CONCLUSIONS: Transabdominal and transcervical chorionic-villus sampling appear to be equally safe procedures for first-trimester diagnosis of fetal abnormalities. PMID- 1640953 TI - Methylprednisolone plus chlorambucil as compared with methylprednisolone alone for the treatment of idiopathic membranous nephropathy. The Italian Idiopathic Membranous Nephropathy Treatment Study Group. AB - BACKGROUND AND METHODS: Treatment with methylprednisolone and chlorambucil may protect renal function and increase the chance of remission of the nephrotic syndrome in patients with idiopathic membranous nephropathy. To determine whether similar results might be obtained with methylprednisolone alone, we compared the effects of methylprednisolone and chlorambucil with those of methylprednisolone alone in 92 patients with the nephrotic syndrome caused by idiopathic membranous nephropathy. The patients were randomly assigned to receive either alternating one-month courses of methylprednisolone and then chlorambucil for a total of six months (group 1) or methylprednisolone alone for six months at the same cumulative dosage (group 2). RESULTS: Four of the 45 patients in group 1 (9 percent) and 1 of the 47 in group 2 (2 percent) stopped treatment because of side effects. At one, two, and three years, the percentage of patients who did not have the nephrotic syndrome was significantly higher in group 1 than in group 2. It was 58, 54, and 66 percent, respectively, in group 1, as compared with 26, 32, and 40 percent in group 2 (P = 0.002, 0.029, and 0.011). By year 4, the difference was no longer statistically significant: 62 percent of the patients in group 1 and 42 percent of those in group 2 did not have the nephrotic syndrome (P = 0.102). The patients in group 1 were in remission longer than those in group 2 (P = 0.008). CONCLUSIONS: In patients with the nephrotic syndrome caused by idiopathic membranous nephropathy, treatment with methylprednisolone and chlorambucil for six months induces an earlier remission of the nephrotic syndrome than methylprednisolone alone, but the difference may diminish with time. PMID- 1640954 TI - Abnormalities of the left temporal lobe and thought disorder in schizophrenia. A quantitative magnetic resonance imaging study. AB - BACKGROUND: Data from postmortem, CT, and magnetic resonance imaging (MRI) studies indicate that patients with schizophrenia may have anatomical abnormalities of the left temporal lobe, but it is unclear whether these abnormalities are related to the thought disorder characteristic of schizophrenia. METHODS: We used new MRI neuroimaging techniques to derive (without knowledge of the diagnosis) volume measurements and three-dimensional reconstructions of temporal-lobe structures in vivo in 15 right-handed men with chronic schizophrenia and 15 matched controls. RESULTS: As compared with the controls, the patients had significant reductions in the volume of gray matter in the left anterior hippocampus-amygdala (by 19 percent [95 percent confidence interval, 3 to 36 percent]), the left parahippocampal gyrus (by 13 percent [95 percent confidence interval, 3 to 23 percent], vs. 8 percent on the right), and the left superior temporal gyrus (by 15 percent [95 percent confidence interval, 5 to 25 percent]). The volume of the left posterior superior temporal gyrus correlated with the score on the thought-disorder index in the 13 patients evaluated (r = -0.81, P = 0.001). None of these regional volume decreases was accompanied by a decrease in the volume of the overall brain or temporal lobe. The volume of gray matter in a control region (the superior frontal gyrus) was essentially the same in the patients and controls. CONCLUSIONS: Schizophrenia involves localized reductions in the gray matter of the left temporal lobe. The degree of thought disorder is related to the size of the reduction in volume of the left posterior superior temporal gyrus. PMID- 1640955 TI - The prevention and treatment of osteoporosis. PMID- 1640956 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 35-1992. An eight-month-old boy with diarrhea and failure to thrive. PMID- 1640957 TI - Membranous nephropathy--still a treatment dilemma. PMID- 1640958 TI - Nucleoside therapy for HIV infection--some answers, many questions. PMID- 1640959 TI - The Oregon Medicaid controversy. PMID- 1640960 TI - The Oregon Medicaid controversy. PMID- 1640961 TI - The Oregon Medicaid controversy. PMID- 1640962 TI - Prophylactic fluconazole and marrow transplantation. PMID- 1640963 TI - Prophylactic fluconazole and marrow transplantation. PMID- 1640964 TI - Prophylactic fluconazole and marrow transplantation. PMID- 1640965 TI - Pregnancy and HIV. PMID- 1640966 TI - Pregnancy and HIV. PMID- 1640967 TI - Preventing neonatal herpes. PMID- 1640968 TI - Preventing neonatal herpes. PMID- 1640969 TI - Demonstration of the transmissible agent in tissue from a pregnant woman with Creutzfeldt-Jakob disease. PMID- 1640970 TI - Pravastatin-associated inflammatory myopathy. PMID- 1640971 TI - The Supreme Court, liberty, and abortion. PMID- 1640972 TI - On gene patenting. PMID- 1640973 TI - Phylogeny of the genera Trichophyton using mitochondrial DNA analysis. AB - Diversity of mitochondrial DNA (mtDNA) was investigated in 92 Trichophyton rubrum strains, 2 T. mentagrophytes var. mentagrophytes, 2 T. m. var. interdigitale, 2 T. m. var. goetzii, 1 T. m. var. erinacei, 2 T. quinckeanum, 2 T. schoenleinii, 1 T. tonsurans, 2 T. verrucosum var. album, 2 T. v. var. discoides, 1 T. violaceum var. violaceum, 1 Arthroderma benhamiae, and 1 A. vanbreuseghemii using endonucleases, Hae III, Msp I, Hind III, Xba I, and Bgl II. Trichophyton species were divided into 7 groups, and a phylogenetic tree was produced based on sequence divergence within mtDNA. The following results were obtained: (1) T. rubrum was divided into 2 groups Type I and Type II, and was suggested to be a complex. (2) A. benhamiae was closely related to T. m. var. erinacei. (3) T. rubrum Type II, T. tonsurans, and A. vanbreuseghemii showed identical restriction profiles, and were suggested to be closely related to each other or identical. (4) T. quinckeanum and T. schoenlenii showed identical restriction profiles, which differed slightly from those of A. vanbreuseghemii. (5) mtDNA analysis was useful in identifying pleomorphic strains. PMID- 1640974 TI - Localized cutaneous nocardiosis in Japan. A new case. AB - We report a case of localized cutaneous nocardiosis due to Nocardia asteroides, appearing on the anterior surface of the right forearm of a 29-year-old woman. Examination of the skin revealed a firm subcutaneous nodule measuring 32 x 20 mm and accompanied with a small ulcer. The histology of the lesion showed granulomatous changes interspersed with large numbers of polymorphonuclear leukocytes. On Gram staining, a few bacillary bodies were found scattered through the lesion, but no grains were detected. The classification of the clinical types of cutaneous nocardiosis is discussed, and the Japanese literature on localized cutaneous nocardiosis is examined. PMID- 1640975 TI - Detection of cellular immunity with the soluble antigen of the fungus Sporothrix schenckii in the systemic form of the disease. AB - Sporothrix schenckii is the etiologic agent of sporotrichosis, a mycosis of world wide distribution more commonly occurring in tropical regions. The immunological mechanisms involved in the prevention and control of sporotrichosis are not fully understood but apparently include both the humoral and cellular responses. In the present investigation, cellular immunity was evaluated by in vivo and in vitro tests in mice infected with yeast-like forms of S. schenckii. The disease developed systemically and cellular immunity was evaluated for a period of 10 weeks. The soluble antigen utilized in the tests was prepared from yeast form of the fungus through the sonication (20 min: 10 sonications at 50 W at 2-min intervals). Delayed hypersensitivity and lymphocyte transformation tests showed that the cellular immune response was depressed between the 4th and 6th week of infection when the animals were challenged with the soluble fungal antigen. This depression frequently indicates worsening of the disease, with greater involvement of the host. This is a promising field of research for a better understanding of the pathogeny of this mycosis. PMID- 1640977 TI - Ultrastructure of the concentric membrane system in Arthrinium aureum. AB - An ultrastructural study was performed on Arthrinium aureum. The fungi were treated with glutaraldehyde and osmium tetroxide fixation. The hypha and conidia has a concentric membrane system which consisted of multiple membranes of a myelinoid appearance, and continued to the conidia and hypha plasma membrane. The fungi were also treated with periodic acid-alkaline bismuth (PABi) staining after glutaraldehyde and osmium tetroxide fixation. PABi positive materials were found on the marginal glycogen granules, the concentric membrane system and the conidia plasma membrane. PMID- 1640976 TI - Pathogenicity of Sporotrichum pruninosum and Cladosporium oxysporum, isolated from the bronchial secretions of a patient, for laboratory mice. AB - In this study we have demonstrated the occurrence of Sporotrichum pruinosum and Cladosporium oxysporum in the bronchial secretions of a patient with a presumptive diagnosis of tuberculosis. This observation coupled with the ability of both fungi to cause infection and elicit tissue responses in experimentally infected mice supported a probable etiologic relationship with the patient which could not be confirmed in the absence of histologic evidence. In vitro some antimycotics were tested against S. pruinosum and C. oxysporum by the agar dilution method. Oxiconazole with a minimum inhibitory concentration of 0.1 micrograms/ml-1 after 72 h and amorolfine at a concentration of 0.001 micrograms/ml-1 after 72 h were the most active ones against S. pruinosum and C. oxysporum respectively. It is suggested that the isolation of S. pruinosum and C. oxysporum from patients with bronchopulmonary disorders should be viewed with caution. Clinical and laboratory evaluation of such patients should be done critically before arriving at a firm diagnosis. PMID- 1640978 TI - IMI descriptions of fungi and bacteria no. 1101. Penicillium aurantiogriseum. PMID- 1640979 TI - IMI descriptions of fungi and bacteria no. 1103. Penicillium camembertii. PMID- 1640980 TI - IMI descriptions of fungi and bacteria no. 1104. Penicillium citrinum. PMID- 1640981 TI - IMI descriptions of fungi and bacteria no. 1105. Penicillium glabrum. PMID- 1640982 TI - IMI descriptions of fungi and bacteria no. 1106. Penicillium islandicum. PMID- 1640983 TI - IMI descriptions of fungi and bacteria no. 1107. Penicillium oxalicum. PMID- 1640984 TI - IMI descriptions of fungi and bacteria no. 1108. Penicillium purpurogenum. PMID- 1640985 TI - IMI descriptions of fungi and bacteria no. 1109. Penicillium roquefortii. PMID- 1640986 TI - IMI descriptions of fungi and bacteria no. 1110. Penicillium viridicatum. PMID- 1640988 TI - Germany links biology centres. PMID- 1640987 TI - EMBL director quits after long fight over expansion. PMID- 1640989 TI - Burris appointed to head Woods Hole marine laboratory. PMID- 1640990 TI - Problems delay emergence of Moscow research centre. PMID- 1640991 TI - Fact and fiction in alignment. PMID- 1640992 TI - Mistaken view. PMID- 1640993 TI - Natural selection. PMID- 1640994 TI - Consciousness on the scientific agenda. PMID- 1640995 TI - Proteins. Folding in the egg white. PMID- 1640996 TI - Chemical kinetics. Probing the transition state. PMID- 1640997 TI - Quicker reaction by design. PMID- 1640998 TI - Signal transduction. Exchange rate mechanisms. PMID- 1640999 TI - How cells know their place. PMID- 1641000 TI - What's in a genome? PMID- 1641001 TI - Earliest Homo debate. PMID- 1641002 TI - Earliest Homo debate. PMID- 1641003 TI - The folding of hen lysozyme involves partially structured intermediates and multiple pathways. AB - Analysis of the folding of hen lysozyme shows that the protein does not become organized in a single cooperative event but that different parts of the structure become stabilized with very different kinetics. In particular, in most molecules the alpha-helical domain folds faster than the beta-sheet domain. Furthermore, different populations of molecules fold by kinetically distinct pathways. Thus, folding is not a simple sequential assembly process but involves parallel alternative pathways, some of which may involve substantial reorganization steps. PMID- 1641004 TI - Retinoblastoma gene product activates expression of the human TGF-beta 2 gene through transcription factor ATF-2. AB - The retinoblastoma susceptibility gene product (pRb) plays an important role in constraining cellular proliferation and in regulating the cell cycle. The pRb inhibits transcription of genes involved in growth control (reviewed in ref. 3) and can regulate transforming growth factor beta 1 (TGF-beta 1) gene expression. TGF-beta isoforms also down-regulate cellular proliferation. To determine whether pRb also regulates expression of other TGF-beta isoforms, we examined the effect of pRb on the expression of the human TGF-beta 2 gene. The human TGF-beta 2 promoter contains multiple elements including an ATF site, which is essential for basal promoter activity. Here we report that pRb activates transcription of the human TGF-beta 2 gene. The promoter element responsible for pRb-mediated transcriptional regulation is a binding site for ATF proteins, an extensive transcription factor family. We provide evidence that implicates ATF-2 in pRb responsiveness. First, the ATF promoter element in the TGF-beta 2 gene is a high affinity ATF-2-binding site. Second, a GAL4-ATF2 fusion protein can support pRb mediated transcriptional activation of a promoter containing GAL4-binding sites. Third, ATF-2 in nuclear extracts can interact with pRb. Our results reveal a new mechanism by which pRb constrains cellular proliferation: by activating expression of the inhibitory growth factor, TGF-beta 2. PMID- 1641005 TI - A strategy tinged with chauvinism. PMID- 1641006 TI - NIH, under fire, freezes grant for conference on genetics and crime. PMID- 1641007 TI - Society asks Brazil's president to resign. PMID- 1641008 TI - British say Pasteur Institute slighted their help on AIDS test. PMID- 1641009 TI - Industry slows research gains in Portugal. PMID- 1641010 TI - British report real decline in spending on research. PMID- 1641011 TI - Japan prepares spending increase. PMID- 1641012 TI - Wellcome Trust to double spending after sale of shares. PMID- 1641013 TI - University officials dismiss quick payoff from research funds. PMID- 1641014 TI - How rare is rare? PMID- 1641015 TI - Humbling of world's AIDS researchers. PMID- 1641016 TI - Developmental biology. The germ of the issue. PMID- 1641017 TI - Marine biology. A phantom of the ocean. PMID- 1641018 TI - Transcriptional regulation. A closer look at E2F. PMID- 1641019 TI - Molecular mimicry in liver disease. PMID- 1641020 TI - Marine isotope evolution. PMID- 1641021 TI - Induction of germ cell formation by oskar. AB - The oskar gene directs germ plasm assembly and controls the number of germ cell precursors formed at the posterior pole of the Drosophila embryo. Mislocalization of oskar RNA to the anterior pole leads to induction of germ cells at the anterior. Of the eight genes necessary for germ cell formation at the posterior, only three, oskar, vasa and tudor, are essential at an ectopic site. PMID- 1641022 TI - New 'phantom' dinoflagellate is the causative agent of major estuarine fish kills. AB - A worldwide increase in toxic phytoplankton blooms over the past 20 years has coincided with increasing reports of fish diseases and deaths of unknown cause. Among estuaries that have been repeatedly associated with unexplained fish kills on the western Atlantic Coast are the Pamlico and Neuse Estuaries of the southeastern United States. Here we describe a new toxic dinoflagellate with 'phantom-like' behaviour that has been identified as the causative agent of a significant portion of the fish kills in these estuaries, and which may also be active in other geographic regions. The alga requires live finfish or their fresh excreta for excystment and release of a potent toxin. Low cell densities cause neurotoxic signs and fish death, followed by rapid algal encystment and dormancy unless live fish are added. This dinoflagellate was abundant in the water during major fish kills in local estuaries, but only while fish were dying; within several hours of death where carcasses were still present, the flagellated vegetative algal population had encysted and settled back to the sediments. Isolates from each event were highly lethal to finfish and shellfish in laboratory bioassays. Given its broad temperature and salinity tolerance, and its stimulation by phosphate enrichment, this toxic phytoplankter may be a widespread but undetected source of fish mortality in nutrient-enriched estuaries. PMID- 1641023 TI - Physiological and behavioural thermoregulation in bigeye tuna (Thunnus obesus). AB - Tuna are unique among teleost fishes in being thermoconserving. Vascular counter current heat exchangers maintain body temperatures above ambient water temperature, thereby improving locomotor muscle efficiency, especially at burst speeds and when pursuing prey below the thermocline. Because tuna also occasionally swim rapidly in warm surface waters, it has been hypothesized that tuna thermoregulate to accommodate changing activity levels or ambient temperatures. But previous field experiments have been unable to demonstrate definitively short-latency, mammalian-type physiological thermoregulation. Here we show using telemetered data that free-ranging bigeye tuna (Thunnus obesus) can rapidly alter whole-body thermal conductivity by two orders of magnitude. The heat exchangers are disengaged to allow rapid warming as the tuna ascend from cold water into warmer surface waters, and are reactivated to conserve heat when they return into the depths. Combining physiological and behavioural thermoregulation expands the foraging space of bigeye tuna into otherwise prohibitively cold, deep water. PMID- 1641024 TI - Neural correlates of perceptual motion coherence. AB - The motions of overlapping contours in a visual scene may arise from the physical motion(s) of either a single or multiple surface(s). A central problem facing the visual motion system is that of assigning the most likely interpretation. The rules underlying this perceptual decision can be explored using a visual stimulus formed by superimposing two moving gratings. The resultant percept is either that of a single coherently moving 'plaid pattern' (coherent motion) or of the two component gratings sliding noncoherently across one another (noncoherent motion). When plaid patterns are configured to mimic one transparent grating overlying another, the percept of noncoherent motion dominates. We now report that neurons in the visual cortex of rhesus monkeys exhibit changes in direction tuning that parallel this perceptual phenomenon: sensitivity to the motions of the component gratings is enhanced under conditions that favour the perception of noncoherent motion. These results challenge models of cortical visual processing that fail to take into account the contribution of figural image segmentation cues to the analysis of visual motion. PMID- 1641025 TI - Specific binding of the transcription factor sigma-54 to promoter DNA. AB - A central event in transcription is the assembly on DNA of specific complexes near the initiation sites for RNA synthesis. Activation of transcription by one class of enhancer-binding proteins requires an RNA polymerase holoenzyme containing the specialized transcription factor, sigma-54 (sigma 54). We report here that sigma 54 alone specifically binds to promoter DNA and is responsible for many of the close contacts between RNA polymerase holoenzyme and promoter DNA, a property proposed for the major sigma 70 protein family. Binding of sigma 54 to promoter DNA is not equivalent to that of holoenzyme suggesting that there is a constraint on sigma 54 conformation when bound with core RNA polymerase. Footprints indicate sigma 54 is at the leading edge of DNA-bound holoenzyme. Like the holoenzyme, sigma 54-binding to promoter DNA does not result in DNA strand separation. Instead the specific DNA-binding activity of sigma 54 assists assembly of a closed promoter complex. This complex can be isomerized to the open (DNA melted) complex by activator protein, but promoter-bound sigma 54 alone cannot be induced to melt DNA. The pathway leading to productive transcription is similar to that proposed for eukaryotic RNA polymerase II systems. PMID- 1641026 TI - Ectopic mesoderm formation in Xenopus embryos caused by widespread expression of a Brachyury homologue. AB - The Brachyrury (T) gene is required cell-autonomously for mesoderm formation in the posterior of the mouse embryo, and both is complementary DNA sequence and expression pattern closely resemble those of a Xenopus homologue (Xbra), suggesting that these genes have an evolutionarily conserved function in vertebrate development. Strong expression of Xbra messenger RNA is found in the ring of involuting mesoderm during Xenopus gastrulation, and the expression of Xbra is an immediate-early response of animal pole blastomeres to mesoderm inducing factors. To assess the role of Xbra in mesoderm formation, we increased its domain of expression in the embryo by microinjection of Xbra transcripts into the animal pole of Xenopus embryos at the one-cell stage. We show that expression of Xbra by cells of the early embryo is sufficient to direct their development into differentiated mesodermal tissues. At the molecular level this response shows a sharp threshold of sensitivity to the dose of Xbra RNA delivered, and we suggest that Xbra may act as a genetic switch initiating posterior mesodermal specification during embryogenesis. PMID- 1641027 TI - An unusual feature revealed by the crystal structure at 2.2 A resolution of human transforming growth factor-beta 2. AB - Transforming growth factor type beta 2 (TGF-beta 2) is a member of an expanding family of growth factors that regulate proliferation and differentiation of many different cell types. TGF-beta 2 binds to various receptors, one of which was shown to be a serine/threonine kinase. TGF-beta 2 is involved in wound healing, bone formation and modulation of immune functions. We report here the crystal structure of TGF-beta 2 at 2.2 A resolution, which reveals a novel monomer fold and dimer association. The monomer consists of two antiparallel pairs of beta strands forming a flat curved surface and a separate, long alpha-helix. The disulphide-rich core has one disulphide bone pointing through a ring formed by the sequence motifs Cys-Ala-Gly-Ala-Cys and Cys-Lys-Cys, which are themselves connected through the cysteines. Two monomers are connected through a single disulphide bridge and associate such that the helix of one subunit interacts with the concave beta-sheet surface of the other. Four exposed loop regions might determine receptor specificity. The structure provides a suitable model for the TGF-beta s and other members of the super-family and is the basis for the analysis of the TGF-beta 2 interactions with the receptor. PMID- 1641029 TI - Welcoming Wellcome. PMID- 1641028 TI - Cloning of cDNAs for Fanconi's anaemia by functional complementation. PMID- 1641030 TI - Healy attacks NASA's claims; bad news for research budgets. PMID- 1641031 TI - Bush delays new risk guidelines. PMID- 1641032 TI - AIDS causation. PMID- 1641033 TI - Sex testing at the Olympics. PMID- 1641034 TI - Developmental biology. Inducing concentric worm holes. PMID- 1641035 TI - Motor neuron diseases. High hopes of a trophic factor. PMID- 1641036 TI - Westhof's rule. PMID- 1641037 TI - The gene lin-3 encodes an inductive signal for vulval development in C. elegans. AB - The lin-3 gene is necessary for induction of the Caenorhabditis elegans vulva by the anchor cell. It encodes a molecule similar to epidermal growth factor and to transforming growth factor-alpha and acts through the epidermal growth factor receptor homologue let-23. Expression of lin-3 in the anchor cell stimulates vulval induction; lin-3 may encode the vulval inducing signal. PMID- 1641038 TI - Human infection by genetically diverse SIVSM-related HIV-2 in west Africa. AB - Our understanding of the biology and origins of human immunodeficiency virus type 2 (HIV-2) derives from studies of cultured isolates from urban populations experiencing epidemic infection and disease. To test the hypothesis that such isolates might represent only a subset of a larger, genetically more diverse group of viruses, we used nested polymerase chain reactions to characterize HIV-2 sequences in uncultured mononuclear blood cells of two healthy Liberian agricultural workers, from whom virus isolation was repeatedly unsuccessful, and from a culture-positive symptomatic urban dweller. Analysis of pol, env and long terminal repeat regions revealed the presence of three highly divergent HIV-2 strains, one of which (from one of the healthy subjects) was significantly more closely related to simian immunodeficiency viruses infecting sooty mangabeys and rhesus macaques (SIVSM/SIVMAC) than to any virus of human derivation. This subject also harboured multiply defective viral genotypes that resulted from hypermutation of G to A bases. Our results indicate that HIV-2, SIVSM and SIVMAC comprise a single, highly diverse group of lentiviruses which cannot be separated into distinct phylogenetic lineages according to species of origin. PMID- 1641039 TI - Ciliary neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuronopathy. AB - Ciliary neurotrophic factor (CNTF) supports the survival of embryonic motor neurons in vitro and in vivo, and prevents lesion-mediated degeneration of rat motor neurons during early post-natal stages. Here we report that CNTF greatly reduces all the functional and morphological changes in pmn/pmn mice, an autosomal recessive mutant leading to progressive caudo-cranial motor neuron degeneration. The first manifestations of progressive motor neuronopathy in homozygous pmn/pmn mice become apparent in the hind limbs at the end of the third post-natal week, and all the mice die up to 6 or 7 weeks after birth from respiratory paralysis. Treatment with CNTF prolongs survival and greatly improves motor function of these mice. Moreover, morphological manifestations, such as loss of motor axons in the phrenic nerve and degeneration of facial motor neurons, were greatly reduced by CNTF, although the treatment did not start until the first symptoms of the disease had already become apparent and substantial degenerative changes were already present. The protective and restorative effects of CNTF in this mouse mutant give new perspectives for the treatment of human degenerative motor neuron diseases with CNTF. PMID- 1641040 TI - Retrograde transport of endocytosed Shiga toxin to the endoplasmic reticulum. AB - Shiga toxin and some other protein toxins that act on targets in the cytosol have previously been shown to enter the trans-Golgi network. Transport by this route may be necessary for translocation of the toxin to the cytosol and for intoxication, but it is not known whether the enzymatically active part of the toxins actually enters the cytosol from the trans-Golgi network. It has been suggested that such toxins are transported in a retrograde manner to the endoplasmic reticulum and that translocation occurs in this organelle, but retrograde transport of endocytosed material beyond the trans-Golgi network has never been demonstrated. Here we show that in butyric acid-treated A431 cells endocytosed Shiga toxin is not only transported to the trans-Golgi network, but also to all Golgi stacks, to the endoplasmic reticulum and to the nuclear envelope. Furthermore, butyric acid sensitizes the cells to Shiga toxin, which is consistent with the possibility that retrograde transport is required for translocation of the toxin to the cytosol. PMID- 1641041 TI - A role for ADP-ribosylation factor in nuclear vesicle dynamics. AB - Two distinct steps in nuclear envelope assembly can be assayed in vitro: the protein-mediated binding of nuclear-specific vesicles to chromatin, and the subsequent fusion of these vesicles to enclose the chromatin within a double nuclear membrane. Nuclear vesicle fusion, like fusion in the secretory pathway, requires ATP and cytosol and is inhibited by nonhydrolysable GTP analogues. The sensitivity of nuclear vesicle fusion to GTP-gamma S requires a GTP-dependent soluble factor, the properties of which are strikingly similar to a GTP-dependent Golgi binding factor (GGBF) that inhibits Golgi vesicle fusion in the presence of GTP-gamma S and belongs to the ADP-ribosylation factor (ARF) family of small GTPases. In the presence of GTP-gamma S, ARF proteins and alpha-, beta-, gamma-, delta-COP ('coatomer') subunits are associated with Golgi transport vesicles, but the exact roles of ARF proteins in secretion are not yet understood. We report here that purified ARF1 and GGBF have GTP-dependent soluble factor activity in the nuclear vesicle fusion assay. Our results show that the function of ARF is not limited to the Golgi apparatus, and indicate that there may be a link between the formation of nuclear vesicles during mitosis and proteins involved in secretion. PMID- 1641042 TI - Moving straight to the target. AB - Retroviral vectors for gene transfer experiments have their limitations--hence the attraction of using other viral vehicles to administer genes directly to affected organs. PMID- 1641043 TI - 32P, 33P and 35S: selecting a label for nucleic acid analysis. AB - The advent of 33P nucleotide triphosphates has widened the options available for labelling nucleic acids. Choosing the most appropriate label requires a careful consideration of experimental needs and circumstances. PMID- 1641044 TI - [Lumbar hernia nuclei pulposi; should not always initially treated conservatively]. PMID- 1641045 TI - [Mother knows best; diagnosis of prelingual deafness]. PMID- 1641046 TI - [Dutch sign language and communication by and with deaf subjects]. PMID- 1641047 TI - [Secondary prevention of ischemic heart disease: a struggle on 2 fronts]. PMID- 1641048 TI - [The provision of hearing aids to young children with congenital hearing impairment]. AB - Early screening for hearing impairment in children is generally advised to prevent sensory deprivation and speech, language and learning problems. In the present study, the age at which 176 probably congenitally hearing impaired infants were referred to the Audiological Centre in Nijmegen between 1983 and 1990 was examined. The mean age of fitting the hearing aids was 35 months. This was about 2 years after the auditory screening test (Ewing test) as performed in most baby health care centres. In general, if a screening test is positive, the child will be referred to the general practitioner, who can refer the child to either a general otolaryngologist or a ENT clinic with a (paedo-) audiological centre. Hearing aids can only be provided by an audiological centre. On average, hearing-impaired children who were directly referred to our clinic/audiological centre were provided with hearing aids 13 months earlier than children initially referred to a general otolaryngologist. It is concluded that young children who fail an auditory screening test should be thoroughly tested audiometrically after an otoscopic examination. PMID- 1641049 TI - [Results of cochlear implants in totally deaf subjects]. AB - Cochlear implants have been applied on a limited scale in the Netherlands since 1985. In a government sponsored health service trial the method was further explored from 1988 to 1991. During this period 20 persons were implanted, ten with a Vienna extracochlear system and ten with a 22-electrode Nucleus intracochlear system. The ages varied from 5 to 62, the duration of deafness from 2 to 47 years. Some patients were congenitally deaf. The major cause of deafness was meningitis. The effect of the implantation was tested with the 'minimal auditory capability' test battery adapted for the Dutch language. 18 persons were wearing their system for more than 8 h a day; one person, a prelingually deaf did no longer use his implant while another one only used it occasionally. Except for two persons, all scored above chance level on several tests. The postlingually deaf persons with the Nucleus system all achieved a certain degree of open set speech understanding without lipreading. With the aim of achieving better selection criteria a new trial has started with the same financial sources in cooperation with the Utrecht University Hospital. PMID- 1641050 TI - [Prevention and control of pain in (adeno)tonsillectomy]. AB - Pain prevention and analgesia in (adeno)tonsillectomy OBJECTIVE. To study the efficacy of three analgesia protocols in children subjected to (adeno)tonsillectomy. SETTING. Twenteborg District Hospital, Almelo, the Netherlands. PATIENTS AND METHODS. In 64 children with body weights ranging from 15 to 25 kg (mean 20.4 kg) subjected to (adeno) tonsillectomy according to the procedure most current in the Netherlands (according to Sluder with administration of a volatile anaesthetic without intubation in day treatment), three protocols for preventing and treating postoperative pain were applied, with the analgetics most current in the Netherlands. Permission from the Medical Ethical Committee and written informed consent from the parents were obtained. According to protocol I 240 mg paracetamol was given, according to protocol II, 500 mg paracetamol and according to protocol III, 500 mg paracetamol plus 10 mg codeine, in suppository form, every 4 hours always starting 60 minutes before operation. Initially, protocol I was carried out, subsequently randomization of protocols II and III. After a pilot study use of a control group was omitted for ethical reasons because of the severe pain in a placebo group. MEASUREMENTS. The efficacy of the analgesia was evaluated by means of pain assessments by the children themselves using the Oucher test, 1, 3 and 6 hours after operation. The statistical processing of the children's pain scores was performed primarily in a descriptive sense, with simultaneous comparison of the three groups using a single variance analysis for comparison of several groups. Multiple comparisons were carried out according to Ducans' multiple range test. The level of significance was put at p less than or equal to 0.05. RESULTS. One hour postoperatively there was no significant difference among the mean pain scores (0: no pain and 10: very bad pain) of the three groups, viz. 5.2 (SD 3.0), 4.7 (SD 2.9) and 4.7 (SD 2.3), respectively; three hours postoperatively there was a significant difference between the mean pain scores of group I (4.5; SD 2.4) and group II (2.7; SD 2.4) but not between group I and group III (3.3; SD 1.5); six hours postoperatively there was a significant difference between the mean pain scores of group I (4.1; SD 2.1) on the one hand and of groups II (2.1; SD 1.5) and III (2.6; SD 1.6) on the other. CONCLUSION. The findings indicate existence of violent pain immediately after recovery from anaesthesia after (adeno)tonsillectomy as shown by the pain assessments by the children themselves one hour postoperatively, in spite of preventive administration of a high dose of a 'minor' analgetic according to each of the three protocols. Modification of the anaesthetic technique should be considered to effect adequate prevention or suppression of pain. PMID- 1641051 TI - [Prevention of blindness in developing countries]. PMID- 1641052 TI - [IGF-1 and phosphate homeostasis during growth]. AB - Inorganic phosphate (Pi) is an essential determinant of cellular growth and replication. IGF-1, a growth hormone dependent factor, enhances at the kidney level both the tubular reabsorption of inorganic phosphate (Pi) and the production of 1,25-dihydroxyvitamin D3. Through these two renal actions IGF-1 increases the extracellular concentration of Pi. Consequently, the amount of Pi available for cellular growth and bone mineral deposition is maintained at a higher level as compared to the concentration prevailing during the adult life. Thus, IGF-1 appears to play a pivotal role in the control of Pi economy, particularly during growth. PMID- 1641053 TI - [Hypophosphatemia of a genetic origin]. AB - Familial hypophosphatemia are either primitive disorders of renal phosphate handling, isolated as in X linked hypophosphatemic rickets (XLHR) or associated with alterations of renal handling of other solutes. They can also occur in the course of a number of other inherited diseases such as vitamin D dependent rickets type I or II and distal tubular acidosis. The molecular basis of most of these diseases are unknown. Chronic hypophosphatemia induces an alteration of bone mineralisation with rickets in children and osteomalacia in children and adults. Hypophosphatemia and the bone disease are most important in XLHR or VDDR. Treatment with oral phosphate and 1 alpha hydroxylated vitamin D metabolites, and in some cases calcium, tends to correct the hypophosphatemia and the bone disease. Treatment of the associated metabolic disorder in certain Fanconi syndromes can correct hypophosphatemia. In the forms associated with hypocalcemia, phosphate therapy is not indicated, but rather calcium therapy. PMID- 1641054 TI - [Parvovirus B19 infection revealed by acute renal insufficiency]. AB - Human adult Parvovirus B19 infection is a well known disease most frequently seen in haematology and cancerology. To our knowledge, however, renal involvement in this context has never been reported. A case of severe infection caused by this virus is reported, where multiple organ involvement is associated with acute renal failure. The outcome was favourable with temporary dialysis and symptomatic treatment. Mechanisms of renal failure, presumably multifactorial, are discussed in the light of this case. PMID- 1641055 TI - [Post-catheterization venous stenosis in hemodialysis: comparative angiographic study of 50 subclavian and 50 internal jugular accesses]. AB - From January 1986 to December 1990, we studied angiographically the subclavian brachiocephalic vein of 100 patients dialysed on subclavian catheter for 50 (first group) and on internal jugular catheter for the 50 others (second group). These 2 groups are not statistically different for age: 61.6 +/- 11.3 years in the first and 61 +/- 11.1 in the second, for sex: respectively 48% and 56% of women, for time-length of catheter insertion: respectively 31 +/- 21.8 days and 31.7 +/- 16, and for number of dialysis sessions: respectively 13.5 +/- 9.1 and 13.6 +/- 7.1. The type of catheters, the frequency of removal for poor flow (16% in both groups) or for infections (6% in both groups) and the local nursing are similar in the 2 groups. Only the side of cannulation differs: the right side is used in 58% of cases in the first group and 78% in the second one. The angiographic study reveals a stenosis of the vein in 42% of the subclavian group and in 10% of the internal jugular group: a dramatic difference in favour of the internal jugular route, whose superiority on subclavian route is asserted in respect of venous access of dialysed patients. PMID- 1641056 TI - [AN 69 membrane and conversion enzyme inhibitors: prevention of anaphylactic shock by alkaline rinsing?]. AB - Thirty-three anaphylactoid reactions occurring in 19 ACE inhibitors-treated patients dialyzed with AN 69 membrane--plate and hollow fibers--dialyzers are reported. A careful analyze of these observations strongly suggests the preventive role of alkaline rinsing of the membrane. PMID- 1641057 TI - [A new model of extramembranous glomerulonephritis in the mouse after a single injection of anti-aminopeptidase A monoclonal antibodies]. PMID- 1641058 TI - Blood-brain exchange routes and distribution of 65Zn in rat brain. AB - Zinc is essential for normal development and function of the CNS although much is to be learned about brain Zn homeostasis. In these experiments adult male Wistar rats within the weight range 500-600 g were used. Ventriculo-cisternal perfusion was performed to allow the measurement of 65Zn fluxes between blood and csf across the choroid plexuses. Blood-brain or blood-cerebrospinal fluid barrier permeability to 65Zn has been determined by graphical analysis in experiments that lasted between 5 and 180 minutes. Cerebral capillary permeability to 65Zn was found to be low with a K(in) of about 5 x 10(-4)ml/min/g. Choroid plexus permeability to 65Zn was about 12 fold greater, although Zn influx to brain via this route was less than 5% that across cerebral capillaries. The autoradiographic distribution of 65Zn in brain showed regional variation with lowest levels in white matter and high levels in the dentate gyrus and hippocampus. PMID- 1641059 TI - A hypothalamic activator of calmodulin-dependent enzymes is thymosin beta 4 (1 39). AB - A new class of stimulators of basal activity of a number of calmodulin-dependent enzymes have been previously isolated from bovine hypothalamus. One of these stimulators, denoted as C3, has been purified to homogeneity by reverse phase HPLC and tentatively identified as thymosin beta 4 (1-39) by mass spectrometry and Edman microsequence analysis. The stimulating effect of C3 on rabbit skeletal muscle MLCK basal activity was compared with that of thymosin alpha 1 and thymosin beta 4 (16-38). Evidence is presented that all the indicated compounds are Ca(2+)-independent high-affinity MLCK stimulators. The potency of the stimulators in activating the enzyme was: C3 greater than beta 4 greater than (CaM+Ca2+) greater than alpha 1. PMID- 1641060 TI - Age-related changes in acetylcholinesterase and its molecular forms in various brain areas of rats. AB - A previous study conducted in this laboratory revealed a decrease in total cholinesterase (total ChE) in the cerebral cortex, hippocampus and striatum in aged rats (24 months) of various strains, as compared with young animals (3 months). The purpose of the present experiments was to extend the study to other brain areas (hypothalamus, medulla-pons and cerebellum) and to assess whether this decrease was dependent on the reduction of either specific acetylcholinesterase (AChE) or butyrylcholinesterase (BuChE) or both. By using ultracentrifugation on a sucrose gradient, the molecular forms of AChE were evaluated in all the brain areas of young and aged Sprague-Dawley rats. In young rats the regional distribution of total ChE and AChE varied considerably with respect to BuChE. The age-related loss of total ChE was seen in all areas. Although there was a reduction of AChE and, to somewhat lesser extent, of BuChE in the cerebral cortex, hippocampus, striatum, and hypothalamus (but not in the medulla-pons or the cerebellum), the ratio AChE/BuChE was not substantially modified by age. Two molecular forms of AChE, namely G4 (globular tetrameric) and G1 (monomeric), were detected in all the brain areas. Their distribution, expressed as G4/G1 ratio, varied in young rats from about 7.5 for the striatum to about 2.0 for the medulla-pons and cerebellum. The age-related changes consisted in a significant and selective loss of the enzymatic activity of G4 forms in the cerebral cortex, hippocampus, striatum, and hypothalamus, which resulted in a significant decrease of the G4/G1 ratio. No such changes were found in the medulla-pons or the cerebellum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641061 TI - Interactions of the neurotoxin MPTP and its demethylated derivative (PTP) with monoamine oxidase-B. AB - The kinetics of the interactions of MPTP and its N-des-methyl-derivative (PTP) have been studied. Both were mechanism-based inhibitors as well as substrates for the enzyme. Analysis of the reaction progress-curves for the formation of the corresponding dihydropyridine derivatives allowed the kinetic parameters for the process and the partition ratio, which corresponds to the number of mol. of product formed per mol. of enzyme inactivated, to be determined for both compounds. The conversion of MPTP to its corresponding pyridinium-ion derivative through the action of MAO-B is known to be essential for its neurotoxicity. PTP has been reported not to be neurotoxic, although it appears to be a relatively good substrate for MAO-B as well as acting as a mechanism-based inhibitor. Studies of the changes in absorbance spectra during the MAO-B catalysed oxidation were consistent with the formation of the corresponding pyridinium-ion derivative (MPP+), which is known to be the effective neurotoxin, as the end-product when MPTP was oxidized. In contrast the oxidation of PTP appeared to stop at the dihydropyridine stage with no significant further oxidation to the corresponding pyridine-derivative. PMID- 1641062 TI - Effects of detergents on Ca(2+)-activated neural proteinase activity (calpain) in neural and non-neural tissue: a comparative study. AB - Calcium activated neutral proteinase (mcalpain) activity was determined in brain and other tissue of rat. More than 60% of the brain mcalpain activity was present in the particulate fraction while only 30% was in cytosol. In contrast, particulate fractions of liver, kidney, muscle, and heart contained about 8-12% of tissue mcalpain activity while 88% was present in cytosol. Removal of the endogenous inhibitor calpastatin increased the tissue mcalpain activity severalfold. Triton X-100 and deoxycholate (DOC) stimulated the neural calpain activity by ten-fold while activity in non-neural tissue was unaffected. Incubation with other detergents, e.g. Triton N-57 and thioglucopyranoside, stimulated brain calpain activity five-fold while Brij-35 did not have any effect. Sodiumdodecylsulphate (SDS), on the other hand, inhibited the enzyme activity. Brain contained the lowest calpain activity compared to non-neural tissue. The calpain activity in muscle, kidney and heart was three-fold greater than liver. Immunoblot identification of the enzyme revealed that calpain was predominantly in the particulate fraction and less in cytosol of brain while it was present mainly in cytosol and less in the pellet fractions of non-neural tissue. PMID- 1641063 TI - Analysis of individual CNS protein synthesis. AB - A procedure for labeling rat CNS proteins in vivo which is useful for behavioral and pharmacological studies has been developed. Intraventricular administration of 35S-methionine through bilateral indwelling cannulae provided reproducible and highly specific radiolabeling of proteins from frontal cortex (FC), parietal cortex (PC), occipital cortex (OC), striatum (ST), septal nuclei (SN), amygdala (AM), hippocampus (HIP), thalamus (TH), brain stem (BS) and cerebellum (CB). Relative rates of synthesis of over 200 individual proteins were subsequently analyzed by 2DGE. Regional analysis demonstrated increased labeling of a protein of MW 28 kD and pI 6.4 in the hippocampus that was barely detectable in striatum of control rats. In heat-shocked animals, there was increased relative synthesis of the 74 kD Heat Shock Protein in both the septal nuclei and hippocampus. PMID- 1641064 TI - Dipeptidase activities in rat brain synaptosomes can be distinguished on the basis of inhibition by bestatin and amastatin: identification of a kyotorphin (Tyr-Arg)-degrading enzyme. AB - The neuropeptide kyotorphin (Tyr-Arg) was degraded by rat brain synaptosomes via a synaptic membrane-bound peptidase which was inhibited by bestatin but not by amastatin. The Km for kyotorphin was 8 x 10(-6) M and the Ki for bestatin was 1 x 10(-7) M. The kyotorphin-degrading enzyme was distinguished from at least one other dipeptide-hydrolyzing activity in synaptosomes which was inhibited by both bestatin and amastatin. Gel permeation chromatography of detergent-extracted synaptosomes resulted in the separation of the dipeptide-hydrolyzing activities. A single kyotorphin-degrading enzyme peak was observed which had a M(r) = 52,000. The activity peak could degrade other dipeptides including Phe-Arg, a synaptic membrane-generated metabolic of bradykinin. The kyotorphin-degrading enzyme appears to be novel and can be distinguished from other known dipeptidases on the basis of substrate specificity, subcellular localization, and inhibition profile. PMID- 1641065 TI - Effects of taurine on the phosphorylation of specific proteins in subcellular fractions of the rat retina. AB - The effects of 20 mM taurine on the phosphorylation of specific proteins in mitochondrial and rod outer segment subcellular fractions of the rat retina were measured. A band of protein with an apparent molecular weight of approximately 20K was consistently inhibited by taurine. Densitometry measurements performed on gel electrophoresis autoradiograms from the mitochondrial fraction demonstrated a 42.7 +/- 8.3% decrease due to taurine (20 mM) in the area corresponding to radioactivity from the approximately 20K phosphoprotein. However, only a 21.2 +/- 9.0% decrease was observed due to taurine in the rod outer segment preparation. These data suggest that taurine is exerting its primary effect on the phosphorylation of the approximately 20K molecular weight protein in the mitochondria of the retina. In addition, calmodulin and phorbol ester had no effect on the phosphorylation of the approximately 20K molecular weight protein. PMID- 1641066 TI - Membrane fluidity of platelets and erythrocytes in patients with Alzheimer's disease and the effect of small amounts of aluminium on platelet and erythrocyte membranes. AB - The membrane fluidity of platelet and erythrocyte membranes in 10 Alzheimer's disease patients and 9 age-matched controls was studied. The platelet membranes of patients with Alzheimer's disease were found to be significantly more fluid than those of controls (p less than 0.02). However, erythrocyte membranes of Alzheimer patients were less fluid (more viscous) than those of controls (p less than 0.05). On further investigation of platelet and erythrocyte membranes obtained from healthy volunteers, the fluidity was found to change with increasing aluminium concentrations. When aluminium ammonium sulphate (0.01-10 microM) was added to membrane suspensions, the fluidity of platelet membranes was increased, whereas the fluidity of erythrocyte membranes was decreased (i.e. the microviscosity was increased). PMID- 1641067 TI - Short history of neuroendocrinology and the International Society of Neuroendocrinology. PMID- 1641068 TI - Noradrenergic innervation of the hypothalamus participates in adrenocortical responses to interleukin-1. AB - Stress and immune activation are associated with increases in plasma concentrations of corticosterone (CS). To determine whether the catecholaminergic innervation of neurons in the hypothalamic paraventricular nucleus (PVN) is involved in these responses, selective lesions were made using 6-hydroxydopamine (6-OHDA). Injection of 6-OHDA into the PVN depleted its norepinephrine (NE) content by 85% and reduced by 80-82% the increase in plasma CS concentrations following intraperitoneal injection of recombinant human interleukin-1 alpha (IL 1), but did not affect the adrenocortical response to 20 min restraint. Injection of 6-OHDA into the ventral noradrenergic ascending bundle depleted PVN NE content by 77%. This lesion reduced the CS response to human IL-1 alpha by 82-86%, but did not alter that to 20 min restraint, although there was a nonsignificant decrease in the CS response following 3 min of restraint. These results suggest that the noradrenergic innervation of the PVN mediates the activation of the hypothalamic-pituitary-adrenal (HPA) axis by intraperitoneally injected IL-1. There may be a noradrenergic contribution to the HPA response to restraint, but other neural pathways probably also participate in this response. PMID- 1641069 TI - Plasma growth hormone and prolactin responses to graded levels of acute exercise and to a lactate infusion. AB - The effect of acute exercise at three graded intensities on plasma growth hormone (GH) and prolactin (PRL) concentrations was examined in three groups of healthy male volunteers. According to their training status these subjects were divided into untrained, moderately trained and highly trained. A clear response of GH to exercise was registered already at an intensity of 50% of maximal oxygen uptake (VO2max) with a maximal response at 70% VO2max and no further effect at 90% VO2max. In contrast, no PRL response was observed at 50% VO2max, a small PRL rise was seen at 70% VO2max and the highest response occurred at 90% VO2max. Basal and exercise-stimulated plasma GH and PRL concentrations were similar in the three groups tested at similar relative workloads, suggesting that physical training induces adaptive changes whereby higher absolute workloads induce similar hormonal and metabolic changes. To examine a potential causative role of lactate in inducing the GH and PRL responses, sodium L-lactate was infused intravenously to normal sedentary volunteers at doses producing plasma lactate concentrations within the range of those seen between 70 and 90% VO2max. This resulted in a significant elevation of plasma GH and PRL concentrations, which, however, were smaller than those obtained at an exercise-induced matched plasma lactate concentration. We conclude that physical training causes adaptive changes in highly trained runners so that identical GH and PRL responses to exercise are recorded at higher absolute workloads. Lactate may be involved in the exercise induced GH and PRL response; however, it does not appear to play an exclusive role. PMID- 1641070 TI - Stimulation and inhibition of growth hormone secretion by interleukin-1 beta: the involvement of growth hormone-releasing hormone. AB - The effects of intracerebroventricularly (i.c.v.) injected interleukin-1 beta (IL 1 beta: 1, 2.5, 10, and 25 ng) were studied on plasma growth hormone (GH) and prolactin (PRL) concentrations in freely moving rats chronically implanted with i.c.v. cannulas and intracardial catheters. Significant changes in PRL secretion were not found. Small i.c.v. doses of IL-1 stimulated GH secretion 15 min postinjection (significant after 2.5 ng IL-1) whereas high doses of IL-1 suppressed plasma GH concentrations. The stimulation of GH secretion by 2.5 ng IL 1 was abolished when endogenous growth hormone-releasing hormone (GHRH) was immunoneutralized by pretreating the rats with GHRH antibodies. The results indicate that IL-1 elicits GH secretion by stimulating the release of hypothalamic GHRH. The inhibition of GH secretion after high doses of IL-1 is attributed to the previously reported corticotropin-releasing-hormone-releasing activity of IL-1. PMID- 1641071 TI - Divergent effects of glucocorticoid on the gene expression of vasoactive intestinal peptide in the rat cerebral cortex and pituitary. AB - We investigated the effects of glucocorticoid on the expression of the vasoactive intestinal peptide (VIP) gene, a neuropeptide and an established prolactin (PRL) releasing factor, in the rat brain and pituitary. The mRNA and peptide contents of VIP in the cerebral cortex, hypothalamus and anterior pituitary of male Sprague-Dawley rats were quantitated 4 weeks after adrenalectomy or sham operation. Following adrenalectomy, VIP mRNA content increased in the anterior pituitary but showed no significant change in the cerebral cortex and hypothalamus. Dexamethasone treatment for 10 days abolished the effect of adrenalectomy and decreased significantly pituitary VIP mRNA content in sham operated rats. In the cerebral cortex, however, dexamethasone treatment resulted in an enhancement in VIP mRNA levels in both sham-operated and adrenalectomized animals. Hypothalamic VIP mRNA content remained unchanged. These changes in VIP mRNA levels were accompanied by parallel changes in VIP concentrations in the tissues studied, suggesting that glucocorticoid regulates the synthesis of VIP in the cerebral cortex and anterior pituitary. On the other hand, serum PRL level increased after adrenalectomy but became suppressed following dexamethasone administration, in parallel with changes in pituitary VIP synthesis. These findings suggest that the effect of glucocorticoid on PRL secretion may be mediated, at least in part, via changes in VIP synthesis and secretion. We conclude that glucocorticoid regulates the expression of VIP in the rat brain, resulting in divergent changes in the cerebral cortex and pituitary. Changes in VIP synthesis and secretion may contribute to the disturbances in brain function and PRL secretion in conditions of glucocorticoid excess. PMID- 1641072 TI - Cytokines stimulate the CRH but not the vasopressin neuronal system: evidence for a median eminence site of interleukin-6 action. AB - Antigen-activated immune cells acutely release cytokines which, besides their effects on the immune system, increase hypothalamopituitary-adrenocortical (HPA) function to counteract the inflammatory process. The present study was designed to test, using in vitro paradigms, whether there exists a hypothalamic and/or a median eminence site of action, whereby different substances derived from the immune system could stimulate the CRH and/or the arginine-vasopressin (AVP) neuronal pathway. For this purpose, whole medial basal hypothalamus (containing the median eminence) were dissected from female rats and incubated in vitro with several concentrations of interleukin-1 (IL-1)beta, interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, thymosin fraction 5 (TF5) or bacterial lipopolysaccharide (LPS). After a 40-min incubation period, the amounts of CRH and AVP released into the incubation medium were measured by specific radioimmunoassays (RIAs). Additional experiments were carried out by superfusing isolated rat median eminence fragments with the different test substances; CRH and AVP released into the medium were also measured by RIAs. The results indicated that IL-1 beta (10(-11) to 10(-7) M), IL-6 (0.06 x 10(-10) to 0.4 x 10( 10) M), TNF-alpha (6 x 10(-9) to 6 x 10(-7) M) and TF5 (5-500 micrograms/ml) but not LPS (1-100 ng/ml) significantly enhanced hypothalamic CRH secretion above baseline in a concentration-related fashion. Additionally, superfusion experiments demonstrated that, among all test substances, only IL-6 possesses a direct and dose-dependent CRH-releasing activity at the median eminence level. Conversely, no preparation enhanced basal AVP release in either in vitro design.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641073 TI - Proteolytic conversion of neurohypophyseal peptides by rat thymocytes: involvement of endopeptidases. AB - The proteolytic conversion of oxytocin and Arg8-vasopressin by purified rat thymocytes was studied at 37 degrees C and physiological pH 7.4. The formed peptide fragments were isolated by high performance liquid chromatography and characterized by amino acid analysis. When oxytocin was incubated with rat thymocytes, oxytocin 1-8 and oxytocin 1-7 were isolated. In contrast, only Arg8 vasopressin 1-8 was found when Arg8-vasopressin was incubated with thymocytes. The formation of oxytocin 1-8, oxytocin 1-7 and Arg8-vasopressin 1-8 was prevented partially by 10(-3) M phenylmethylsulfonyl fluoride and iodoacetamide, and abolished by 0.5 x 10(-3) M Zn2+ and Hg2+ ions and 10(-3) M o-phenanthroline, but not by 10(-5) M leupeptin, lima bean trypsin inhibitor, trasylol, captopril and phosphoramidon. 0.5 x 10(-3) M EDTA was without effect on the formation of oxytocin 1-8 and Arg8-vasopressin 1-8 but increased by about 30% the formation of oxytocin 1-7. The results suggest that proteases capable of metabolizing oxytocin and Arg8-vasopressin are localized in the thymocyte surface membrane. Since oxytocin and vasopressin are synthetized by thymic epithelial cells and exert several actions on thymocytes, these proteases may play a physiological role in the inactivation of neurohypophyseal peptides at the thymocyte level. PMID- 1641074 TI - Interleukin-1 beta and interleukin-6 specifically increase the release of prostaglandin E2 from rat hypothalamic explants in vitro. AB - It has previously been shown that the cytokines interleukin-1 beta and interleukin-6 (IL-1 beta and IL-6) stimulate directly the release of corticotrophin-releasing-hormone-41 from the rat hypothalamus in vitro, while IL 1 beta can also stimulate the release of somatostatin. These effects can be antagonized by drugs which block prostaglandin (PG) synthesis. PGs are also involved in the control of hypothalamic neuropeptides by other neurotransmitters. In the present study, we have characterized the production of PGs from the rat hypothalamus in vitro, and investigated the effects of IL-1 beta and IL-6, as well as the neurotransmitters norepinephrine, acetylcholine and 5 hydroxytryptamine, on the acute release of PGs, using a well-validated acute hypothalamic incubation system. The rate of release of PGs [PGE2, PGF2 alpha, 6 keto-PGF1 alpha (6KPGF1 alpha) and thromboxane B2 (TXB2) in the medium was found to stabilize after 60 min of preincubation and thereafter remain constant, with TXB2 being the predominant species. Twenty-minute incubation in the presence of human recombinant IL-1 beta or IL-6, in the dose range 1-100 U/ml, had no effect on the release of PGF2 alpha, 6KPGF1 alpha or TXB2; however, the release of PGE2 was significantly increased by both IL-1 beta and IL-6. The effect of IL-1 beta was antagonized by both indomethacin and dexamethasone. None of the other neurotransmitters tested had any effect on the release of any of the PGs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641075 TI - Identification of inositol 1,4,5-trisphosphate binding in human pheochromocytoma. AB - An attempt was made to identify a specific binding of inositol 1,4,5 trisphosphate (IP3) to human chromaffin cell tumors. Crude microsomal fractions of pheochromocytomas possessed significant binding sites for [3H]IP3 with high- and low-affinity constants (Kd = 5.46 and 538 nM, respectively). The binding to these sites was rapid, saturable (reached equilibrium by 1 min at 0 degrees C) and reversible. Competition studies with other inositol phosphate analogs indicated the stereotypic specific binding for IP3. Although no significant difference was observed in the binding densities of IP3 between pheochromocytomas and adrenal nonfunctioning adenomas, the values of high-affinity constants were significantly lower in the former than the latter group (5.77 +/- 1.07, n = 5 vs. 11.30 +/- 1.98 nM, n = 4, p less than 0.05). The present data indicate that characteristics of IP3 binding sites are congruous with their receptor functions and that changes in its binding sites may contribute to the biochemical dissimilitudes in pheochromocytomas. PMID- 1641076 TI - Behavioral action of estrogen in the male dove brain: area differences in codistribution of aromatase activity and estrogen receptors are steroid dependent. AB - Brain aromatization of androgen to estrogen (E) and presence of estrogen-receptor (ER) containing cells (ERC) are required for the control of E-dependent neural events under-lying male sexual behavior. We examined whether (a) numbers of ERC and steroid-inducible aromatase activity are codistributed and directly correlated in the same brain areas of individual sexually active male doves and whether, (b) distribution of ERC is altered by a change in E formation in preoptic areas known to be involved in control of male behavior. To allow spatial correlation between ERC and aromatase activity, a new approach was used that combined in vitro measurement of aromatase activity (stereospecific formation of 3H2O from [1 beta-3H]-testosterone) in microdissected brain areas of one side of the brain and immunocytochemical localization of ERC (ER antibody H222Spy) in homologous contralateral areas of the same coronal brain section. The relationship between ERC and aromatase activity differs according to brain area in sexually active males: (a) large populations of ERC in preoptic areas, notably in nucleus preopticus medialis (6.5 +/- 0.8 ERC/5,000 microns2) and nucleus preopticus medialis, pars medianis (9.5 +/- 1 ERC/5,000 microns2) are codistributed with high steroid-dependent aromatase activity (greater than 100 fmol/mg tissue); (b) areas containing the nucleus interstitialis and ventromedial hypothalamic nuclei also have relatively high aromatase activity, but lower ERC density than POA; (c) the anterior hypothalamic nuclei have few ERC, but steroid regulated aromatase activity; (d) the infundibular area contains elevated ERC and little steroid-inducible aromatase activity; (e) area basalis and neostriatum contain few or no ERC and no inducible aromatase activity. Castration of sexually active doves reduces aromatase activity in preoptic and posterior hypothalamic areas (by greater than 75%) to basal levels, but does not affect the distribution or number of ERC in brain areas containing steroid-regulated aromatase activity, notably in the preoptic area. The results show that steroid regulation of aromatase occurs in brain loci with high numbers of ERC. We suggest that steroid inducible aromatase occurs in brain loci with high numbers of ERC. We suggest that steroid-inducible aromatase activity and ERC are codistributed in areas controlling male sexual behavior; thus the formation and action of E may occur in the same area. Regulation of the aromatase activity and supply of E, but not of number of cells containing ER, is one mechanism which accounts for changes in action of testosterone on estrogen target sites in the male brain. PMID- 1641077 TI - Changes in follicle-stimulating hormone secretion in spontaneously hypertensive rats. AB - FSH and testosterone plasma levels, pituitary FSH content and concentration and the weight of testis, seminal vesicles and ventral prostate have been studied at the ages of 30, 60 and 90 days in spontaneously hypertensive rats (SHR) and normotensive control (WKY) rats. In vitro FSH secretion by pituitaries, and the response to orchidectomy and to exogenous administration of either LHRH (1 microgram) or LHRH agonist (0.05, 0.1, 1, and 5 micrograms/kg) were analyzed in 90-day-old SHR and WKY male rats. Ventral prostate weight and FSH plasma levels were determined in other groups of adult male rats castrated and castrated and implanted for 15 days with silastic capsules containing testosterone, dihydrotestosterone or estradiol. Also FSH plasma levels and pituitary FSH concentration were determined at the ages of 30, 60 and 90 days in SHR and WKY female rats. Male SHR showed increased plasma FSH levels and high testicular weight in all the cases, and enhanced testosterone levels in plasma and pituitary FSH content on days 60 and 90. Weight of seminal vesicles and ventral prostate was normal or reduced, depending on the animal age. Adult SHR had increased FSH secretion in vitro, normal response to orchidectomy and did not exhibit FSH increases after LHRH administration. The efficiency of testosterone to stimulate ventral prostate growth and the ability of estradiol to reduce FSH plasma levels were decreased in SHR. Female SHR showed a significant increase in the pituitary content of FSH on day 30 and on proestrus at the ages of days 60 and 90.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641078 TI - CNS in congenital muscular dystrophy without mental retardation. AB - We have evaluated the CNS findings of 30 patients with congenital muscular dystrophy and normal mental development. The intelligence was estimated by psychological testing or school performance. There were more children of above average intelligence than expected. Neuroradiological examination was done to 15/17 patients still alive. White matter changes were seen in five and cerebral atrophy in four patients. Three patients had epilepsy, two mild, one drug resistant. The EEG did not reveal any common pattern, though there were various abnormalities in several children. PMID- 1641079 TI - Immunotherapy with stimulated autologous lymphocytes in a case of a juvenile anaplastic glioma. AB - The effect of immunotherapy with stimulated autologous lymphocytes (SAL) in malignant gliomas is documented and discussed in a bioptical and autoptical case study. A five-year-old child with a recurrently operated and radiated right hemispheric anaplastic astrocytoma died six weeks after immunotherapy with mitogen-activated killer cells and recombinant Interleukin-2. The autopsy revealed a large butterfly glioma with partially necrotic gelatinous tissue at the site of the SAL reservoir. The tumor cell density on the right was less than on the left hemisphere, and T-lymphocyte content was higher on the right hemisphere. These results demonstrate a local effect of SAL therapy in vivo, although the tumor progression as a whole could not be stopped. They also demonstrate the need of a detailed neuropathological examination in all cases of immunotherapy of malignant gliomas. PMID- 1641080 TI - Acute changes in cerebral oxygenation and cerebral blood volume in preterm infants during surfactant treatment. AB - Following administration of surfactant a marked depression in aEEG activity occurs for about 10 minutes; the mechanism of this depression is unknown. In view of this, twenty-nine preterm infants were investigated with near infrared spectroscopy (NIRS) to evaluate rapid changes in total cerebral haemoglobin concentration and cerebral oxyhaemoglobin concentration during rescue treatment with natural surfactant. During surfactant instillation there was a short-lasting hypoxaemia as demonstrated by pulseoximetry as well as a considerable fall in arterial blood pressure. With NIRS, tissue hypoxia was demonstrated by a drop in cerebral oxyhaemoglobin concentration. The marked drop in arterial blood pressure occurring immediately following surfactant was not matched by a drop in total cerebral haemoglobin concentration. This suggests that cerebral blood volume and hence cerebral blood flow was maintained. In the following minutes there was an improvement in cerebral oxygenation as indicated by the rise in cerebral oxyhaemoglobin concentration in nearly all the infants. PMID- 1641081 TI - Mutism after cerebellar medulloblastoma surgery. AB - The case of a 9-year-old boy is presented, who developed transient mutism after removal of a medulloblastoma in the region of the cerebellar vermis. The mutism disappeared within 6 months. Neither reduction of consciousness nor disturbances of caudal cranial nerves or phonation ever appeared. The case is discussed with regard to its phenomenology, pathogenesis, and etiology, corresponding case reports are also taken into consideration. PMID- 1641082 TI - Leigh syndrome associated with a deficiency of the pyruvate dehydrogenase complex: results of treatment with a ketogenic diet. AB - A one-year-old boy suffering from intermittent lactic acidosis, muscular hypotonia, horizontal gaze paralysis and spasticity in both legs had low activity of the pyruvate dehydrogenase complex associated with low amounts of immunoreactive E 1 alpha and E 1 beta. Leigh syndrome was diagnosed on the basis of the clinical and biochemical abnormalities and the typical lesions observed on MRI of the brain. Treatment with a ketogenic diet was associated with clinical and biochemical amelioration. A striking improvement of the cerebral lesions was observed by neuro-imaging. PMID- 1641083 TI - Unilateral thalamic haemorrhage in the pre-term and full-term newborn. AB - One full-term and three premature newborns with a unilateral thalamic haemorrhage are reported. The lesion was diagnosed using cranial ultrasonography and confirmed in three using magnetic resonance imaging. Severe perinatal asphyxia occurred in all infants. The neonatal clinical history, subsequent neuro developmental outcome and neuroimaging findings are discussed. As the prognosis appears to be much better than for infants with bilateral thalamic densities, it is important that this type of lesion is recognised as a separate entity. PMID- 1641084 TI - Encephalopathy of infancy with intracerebral calcification and chronic spinal fluid lymphocytosis--another case of the Aicardi-Goutieres syndrome. AB - Another case of the Aicardi-Goutieres syndrome is presented. The female child was diagnosed at 4 months of age, when irritability, lack of fixation and dystonic movements were noted. Also, extensive intracerebral calcification was found on computed tomography. Nuclear magnetic resonance imaging confirmed extensive white matter disease. Repeated examination of the spinal fluid revealed chronic spinal fluid lymphocytosis. This condition belongs to the encephalopathies of infancy with intracranial calcification of genetic aetiology and unknown pathogenesis. Differentiation against other presumed entities in this group, as well as the wider differential diagnosis, are discussed. PMID- 1641085 TI - Early epileptic encephalopathy with suppression bursts and olivary-dentate dysplasia. AB - A case of neonatal epileptic encephalopathy with suppression-bursts associated with olivary dentate nuclei dysplasia is reported. This unusual association shows that the so-called Ohtahara syndrome could correspond to several different brain malformations sometimes disclosable only by neuropathological examination. PMID- 1641086 TI - Middle cerebral artery occlusion in rats: a neurological and pathological evaluation of a reproducible model. AB - Middle cerebral artery occlusion (MCAO) in rats produces an infarct of varying size. We examined three factors that may influence this variability: animal weight, vascular anatomy, and extent of occlusion in rats undergoing MCAO. We also developed a four-point neurological evaluation scale and validated its usefulness by comparing it with a four-grade pathological determination of the size of the infarct. Of 82 animals subjected to a standard MCAO, 34 developed small cortical infarcts (pathological grades I-II; infarct size less than 25 mm2, 6-17% of the ipsilateral cortex surface area), and 48 large infarcts (pathological grades III-IV, infarct size greater than 25 mm2, 20-56% of surface area). We were able to predict the size of infarction from the neurological evaluation in 83% of the animals, and this accuracy reached 91% when grades I and II and III and IV were considered together (P less than 0.001). In 41 animals subjected to a more extensive vascular occlusion, 89% exhibited large infarcts. Four vascular patterns were identified but none played a significant role in the incidence or size of the cortical stroke. However, rats weighing less than 300 g showed a smaller lesion size than did rats greater than 300 g. Our proposed new MCAO technique appears useful in reproducing large-sized infarcts of the frontoparietal cortex. PMID- 1641087 TI - Histological comparison of autogenous canine fascia lata, Gore-Tex, lyophilized human fascia lata, and autogenous canine vein for vascular patch graft material in a canine arteriotomy model. AB - Autogenous fascia lata has found little clinical use as a vascular patch graft material. Previous experience, however, suggests that it possesses attributes that might make it useful in this regard. To assess its efficacy as a vascular patch graft, nine adult mongrel dogs each underwent four arteriotomies with placements of patch grafts. The four sites included both carotid arteries and both femoral arteries. In each animal, one of four patch graft materials (autogenous canine fascia lata, Gore-Tex, lyophilized human fascia lata, and autogenous canine vein) were placed as patch material at the arteriotomy site utilizing 7-0 running sutures and loop magnification. The site for placement of each graft material was rotated serially in the animals so that each site would have equal numbers of all four graft materials applied. The animals were killed at either 6 to 8 weeks or 11 to 12 weeks after angiography of all four vessels. The specimens were then evaluated histologically. No difference was observed among any of the patch graft materials with regard to myofibroblast plaque formation. Inflammatory responses were noted to be substantially less in the canine fascia lata group than in the other three groups. Granuloma formation, however, appeared to be most significant in the autogenous canine vein group. Only one vessel was occluded. Aneurysm or pseudoaneurysm formation was not noted in any specimen. It appears from the above results that autogenous fascia lata may be an appropriate alternative to currently utilized arterial patch graft materials and that it should be evaluated further for this purpose. PMID- 1641088 TI - Giant bilateral xanthogranulomas in a child: case report. AB - Symptomatic xanthogranulomas are rare lesions that most commonly occur in adults. A case of giant bilateral xanthogranulomas in a 6-year-old boy, who remains without tumor recurrence 9 years after resection, is presented. The operative management of these unusually large lesions is discussed. The pathogenesis of xanthogranulomas is reviewed as it relates to the presentation of these lesions in the pediatric population. PMID- 1641089 TI - Dural arteriovenous malformation in the cervical spine presenting with subarachnoid hemorrhage: case report. AB - Most spinal dural arteriovenous malformations are located in the thoracic and lumbar regions. The symptoms include pain, weakness, sensory disturbances, and sphincter dysfunction, which are usually gradual in onset. They are attributed to venous hypertension with a resultant ischemia of the cord, and hemorrhage from them is rare. The authors report an unusual case of a patient with a dural arteriovenous malformation in the cervical spine who was admitted with a sudden onset of severe headache and dysesthesia due to subarachnoid hemorrhage. PMID- 1641090 TI - Intramedullary epidermoid cyst of the cervical spinal cord associated with an extraspinal neuroenteric cyst: case report. AB - A 4-year-old girl presented with an intramedullary epidermoid cyst of the cervical spinal cord. The clinical, radiological, and surgical features and a brief critical review of the literature are included in this report. The cyst contents were removed totally in two operations. The child had a coexisting neuroenteric cyst in the posterior mediastinum. To our knowledge, this coexistence has not been previously reported. Contemporary imaging modes and prospects of the surgical treatment are discussed. PMID- 1641091 TI - Ectasia and fenestration of the anterior cerebral artery associated with persistent trigeminal artery: case report. AB - Multiple vascular anomalies in a 22-year-old patient who had signs and symptoms of vestibulocochlear dysfunction are reported. Angiography revealed a fenestration of the proximal segment of the left anterior cerebral artery, an ectasia of the left anterior and posterior cerebral arteries, and a persistence of the right trigeminal artery. The rarity of the association is documented, and the clinical significance is discussed. PMID- 1641092 TI - Acute subdural hematoma after aneurysmal rupture; evacuation with aneurysmal clipping after emergent infusion computed tomography: case report. AB - A 74-year-old woman sought treatment after an initial subarachnoid hemorrhage verified on computed tomographic scan with no focal neurological deficit. Shortly after admission, she sustained a second subarachnoid hemorrhage with acute neurological decompensation. A repeat computed tomographic scan revealed increased blood along the right medial temporal region, as well as in the interhemispheric fissure and bilateral sylvian cisterns. Also evident was a right hemispheric acute subdural hematoma. The patient's rapidly deteriorating neurological status precluded a cerebral angiogram; therefore, a double-dose infusion computed tomographic scan was performed. This revealed a cerebral artery aneurysm adjacent to the right medial temporal hematoma. She was taken to the operating room on the basis of this study. After evacuation of the right hemispheric subdural hematoma and clipping of the right posterior communicating artery aneurysm, the patient made a rapid, full neurological recovery. PMID- 1641093 TI - Sarcomatous transformation in cranial chordoma. AB - In a study of 52 patients with cranial chordoma treated at the Mayo Clinic over a 19-year period (1966-1984), two tumors showed anaplastic features, both de novo, i.e., unassociated with prior irradiation. The incidence of anaplastic transformation was thus 4%. Immunohistochemistry showed the mixed mesenchymal epithelial phenotype typical of chordoma in portions of both tumors, but loss of reactivity for keratin and epithelial membrane antigen was noted in anaplastic components. The study indicates that sarcomatous change in chordoma is a rare event that may occur de novo and is associated with the loss of immunophenotypic features of epithelial differentiation. PMID- 1641094 TI - Multiple arteriovenous malformations located in the cerebellum, posterior fossa, spinal cord, dura, and scalp with associated port-wine stain and supratentorial venous anomaly. AB - Multiple arteriovenous malformations involving the left cerebellum and extra axial posterior fossa with associated calcified cyst, spinal cord, dura, and scalp were present in a 7-year-old girl, who became symptomatic after a cerebellar hemorrhage. A large port-wine stain was noted on the right temporoparietal scalp, consistent with the scalp arteriovenous malformation area, as demonstrated by angiogram. In addition to the multiple arteriovenous malformations, nonfilling of the superior sagittal sinus and tortuous, irregular cortical veins were recognized. PMID- 1641095 TI - Extracranial-intracranial arterial bypass after cerebral foreign body embolization: effective treatment of transient ischemic attacks. AB - A case of traumatic foreign body embolism into the right intracranial carotid artery with stenosis of the right middle cerebral artery in a 9-year-old boy is presented. Initial hemiparesis and a consecutive asymptomatic interval of 12 months were followed by a period of frequent transient ischemic attacks. After an extracranial-intracranial arterial bypass had been performed 18 months later, symptoms ceased without relapse. A thorough review of the literature demonstrates the rare incidence of this entity. PMID- 1641096 TI - Pure motor hemiparesis with stable somatosensory evoked potential monitoring during aneurysm surgery: case report. AB - We report a patient who sought treatment for an acute subarachnoid hemorrhage as a result of an intracranial aneurysm. Management included early surgical repair and intraoperative monitoring of evoked potentials. Pan-angiography revealed berry aneurysms of the communicating anterior artery and right middle cerebral artery. Surgery was uneventful, and the somatosensory evoked potential monitoring did not show any abnormalities. Nevertheless, the patient showed a neurological deficit due to a clip-related infarct in the right middle cerebral artery territory characterized by a right hemiparesis with no sensory deficit. This case report supports the possibility of false-negative results in single-mode intraoperative monitoring during aneurysm surgery. PMID- 1641097 TI - Arteriovenous malformation of the pyriformis muscle manifesting as a sciatic nerve tumor. AB - We present a patient with an intramuscular pelvic arteriovenous malformation that was initially diagnosed as a tumor of the sciatic nerve sheath. Endovascular embolization, attempted as a preoperative maneuver, was complicated by diffuse pulmonary emboli and death. To our knowledge, this is the first such reported case. Its presentation here broadens the differential diagnosis of sciatic nerve sheath tumors, emphasizes the diagnostic and management issues of masses presenting as peripheral nerve tumors, and provides clinicopathological evidence regarding the cause of neurological symptoms. PMID- 1641098 TI - Patient positioning for the operative approach to midline intracerebral lesions: technical note. AB - Patients undergoing craniotomies for intracerebral lesions are generally positioned in such a way that the lesion is highest in the field. For midline lesions alongside the falx, patients are commonly positioned on their backs for an anatomically symmetrical approach. We propose positioning the patient in the lateral decubitus position ipsilateral to the lesion to take advantage of gravity by allowing the brain to fall away from the midline, thus obviating the need for retraction. We have used this position in 15 cases of falcine and parafalcine tumors to great advantage, without encountering untoward operative or anesthetic complications. PMID- 1641099 TI - Closure of posterior fossa dural defects using a dural substitute: technical note. PMID- 1641100 TI - Flow regulated suction tube: technical note. PMID- 1641101 TI - Modification of the standard myelography tray for universal precautions: technical note. PMID- 1641102 TI - Intracranial infection after missile injuries to the brain: report of 30 cases from the Lebanese Conflict. PMID- 1641103 TI - The effect of graded spinal cord injury on the extrapyramidal and pyramidal motor evoked potentials of the rat. PMID- 1641104 TI - Intraoperative angiography in the management of neurovascular disorders. PMID- 1641105 TI - Cerebral arteriovenous malformations associated with a straight sinus anomaly. AB - Nine cerebral arteriovenous malformations (AVM) associated with straight sinus anomaly were demonstrated on angiograms. All 10 AVM (1 patient had two AVM) occupied deep cerebral structures: Seven were totally or partially located in the basal ganglia or the corpus callosum, and 3 were in the medial occipital or temporal lobe. In 6 patients, almost no filling of the straight sinus was observed, although the AVM were located deeply and the main drainage was via the vein of Galen. All 6 patients showed retrograde flow in the deep cerebral veins or venous drainage through a persistent facial sinus. The other 3 patients had duplication or septal formation of the straight sinus. Straight sinus anomaly is extremely rare in the normal population but seems not uncommon in patients with deep-seated AVM. PMID- 1641106 TI - Factors affecting operative and excess long-term mortality in 935 patients with intracranial meningioma. AB - Between 1953 and 1980, a total of 935 patients underwent surgery for intracranial meningioma in the Department of Neurosurgery of the Helsinki University Hospital. The patients were followed up until death or the end of the year 1987. The cumulative observed survival rate was 91% at 3 months, 89% at 1 year, and 63% at 15 years. The relative survival rate, that is, the ratio of the the observed and the expected rates, was 91% at 3 months, 89% at 1 year, and 78% at 15 years. Significant risk factors for operative mortality (7%) for the 652 patients operated on from 1966 to 1980 were poor preoperative clinical condition, absence of epilepsy, old age, incomplete tumor removal, pulmonary embolism, and an intracranial hematoma requiring evacuation. For those 828 patients who survived the first postoperative year, the factors predicting an excess risk of death for up to 15 years were incomplete tumor removal, poor pre- and postoperative clinical condition, anaplasia of the tumor, and hyperostosis. Patients whose tumors were not completely removed had a 4.2-fold relative excess risk of death as compared with patients whose tumors were completely removed, and patients who had malignant tumors had a 4.6-fold risk as compared with those who had benign tumors. PMID- 1641107 TI - Improved cerebral blood flow and CO2 reactivity after microvascular anastomosis in patients at high risk for recurrent stroke. AB - The medical community has not yet identified cerebrovascular pathophysiological factors that distinguish patients at high risk for stroke or aid in selecting patients for microvascular cerebral bypass. In this study, we describe the courses of 13 patients, all of whom suffered recurrent episodes of transient cerebral ischemia after previous cerebral infarction. These patients underwent regional cerebral blood flow studies using xenon inhalation with a CO2 challenge before and at various times after extracerebral-to-intracerebral microvascular anastomosis. Collateral circulation was assessed in all patients before surgery using four-vessel cerebral angiography. Patients were followed for a mean of 30 months (range, 1-7 yr) after the anastomosis. Measurements of mean cortical cerebral blood flow, as measured using the initial Slope Index, and CO2 cerebrovascular reactivity of these 13 patients were compared with those in a group of 20 patients designed as controls. Hemispheric cortical blood flow was significantly depressed in these patients before surgery compared with those in the control group (P less than 0.05). After the bypass, the mean resting Initial Slope Index in these patients increased 14% (P = 0.0005). Cerebral blood flow both before and after CO2 inhalation improved significantly in these patients after surgery (P = 0.001). Detectors bordering computed tomographic or magnetic resonance image documented infarctions, identified as peri-infarct regions, and demonstrated significant mean increases in both cerebral blood flow (38.8-43.2 ml/min/100 g, P = 0.05) and CO2 cerebrovascular reactivity in these patients after bypass (1.71 + 1.91% to 4.00 + 2.38% change Initial Slope Index/mm Hg CO2, P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641108 TI - Rapid expansion of hypertensive intracerebral hemorrhage. AB - We report a series of 10 patients who had a rapid expansion of a hypertensive intracerebral hemorrhage (HICH). It occurred in approximately 3% of 320 patients who sought treatment for HICH during the past 2 years. The site of hemorrhage was the putamen in 6 patients and the thalamus in 4 patients. Neurological deterioration occurred in a mean time of 40 hours after the onset of symptoms (range, 5.5-109 h). Fifty percent of all patients deteriorated within 24 hours. Persistent hypertension was recorded in all patients. Repeat computed tomography showed an increase of hematoma volume that was twice as large in thalamic hemorrhage and about three times as large in putaminal hemorrhage. Six patients died, whereas 3 survived with severe disability and 1 survived with moderate disability. This study indicates that continued or subsequent bleeding can occur in HICH. If those lesions are not detected early and microsurgically evacuated, they are almost always fatal. Early stereotactic evacuation with urokinase irrigation is considered more dangerous than open craniotomy by microsurgical techniques. We stress the need for attention to this problem during the acute phase of HICH. PMID- 1641109 TI - Levels of catecholamine in plasma and cerebrospinal fluid in aneurysmal subarachnoid hemorrhage. AB - Despite intensive investigation into the cause of cerebral vasospasm (focal ischemic deficit) after subarachnoid hemorrhage, the morbidity and mortality associated with this condition remain high. Various studies have shown levels of catecholamine in plasma and cerebrospinal fluid (CSF) to be increased in subarachnoid hemorrhage, and it is possible that these vasoactive substances play an important role in the subsequent vasospasm. In an attempt to elucidate this possibility, the study presented here was undertaken to investigate the relationship between catecholamine levels in plasma and CSF and focal ischemic deficit (FID); the rupture of aneurysms on blood vessels supplying the hypothalamus as compared with the rupture of aneurysms on blood vessels supplying other areas of the brain; and the clinical outcome of the patients. Concentrations of adrenaline and noradrenaline in plasma and CSF samples obtained from 21 patients who had suffered aneurysmal subarachnoid hemorrhage were determined by a radioenzymatic technique. Significantly higher levels of adrenaline were found at the time of surgery in the CSF of patients with FID. A similar trend, though not statistically significant, was also observed for plasma. Patients with a rupture of aneurysms on blood vessels supplying the hypothalamus showed a tendency towards higher catecholamine levels in plasma and CSF. Subjects with a bad clinical outcome (i.e., those who were severely disabled or had died) had significantly higher levels of catecholamine in plasma than did those with a good clinical outcome (i.e., those with moderate or no disability). Further detailed analysis of the interrelationships showed that, within the group of patients with FID, those with rupture of aneurysms on blood vessels supplying the hypothalamus had significantly higher catecholamine levels in plasma than did those with rupture of aneurysms on other cerebral vessels. Furthermore, in the group of patients with rupture of aneurysms on blood vessels supplying the hypothalamus, those with a bad clinical outcome had significantly higher catecholamine levels in plasma than did those with a good clinical outcome. These findings lend support to the possibility that damage to the hypothalamus and subsequent elevations in catecholamine levels may be associated with FID and poor clinical outcome. PMID- 1641110 TI - External ventricular drainage for treatment of rapidly progressive posthemorrhagic hydrocephalus. AB - Twenty-seven newborn infants (birth weight, 1503 +/- 776 g; gestational age, 31 +/- 3 wk) (mean +/- standard deviation) with rapidly progressive posthemorrhagic hydrocephalus and increased intracranial pressure were treated by external ventricular drainage. The progression of hydrocephalus was arrested during the drainage period in each patient. The drainage was kept in place for 23 +/- 9 days, the longest drainage period being 48 days. In 16 of 23 surviving patients, progressive ventricular dilation recurred after removal of the drainage, requiring a definitive shunt implantation (nine ventriculoatrial, seven ventriculoperitoneal). For the remaining seven infants, no further therapy was necessary. Implantation of the permanent shunt was done days 28 to 88 (body weight, 2400 +/- 950 g). Bacterial cultures from cerebrospinal fluid and/or the tip of the ventriculostomy catheter were negative in 175 instances and positive in 11 instances (7 patients). No clinical or biochemical evidence of ventriculitis was noted. Four of the 27 patients died of causes unrelated to external ventricular drainage. Twenty-three infants survived. Seventeen of 23 survivors suffered from intraventricular hemorrhage Grade 3; in 7, neurological and developmental outcomes were classified as normal; 9 patients experienced mild to moderate paresis and/or mild to moderate developmental delay; and only 1 patient was severely retarded. Six patients with parenchymal lesions had severe motor and/or developmental handicaps. We consider external ventricular drainage an effective and safe therapy in newborn infants with rapidly progressive posthemorrhagic hydrocephalus and increased intracranial pressure. The ultimate outcome, however, depends mainly on the mode and the extent of the primary brain lesion. PMID- 1641111 TI - Motor and sensory cortex in humans: topography studied with chronic subdural stimulation. AB - Classic neurosurgical teaching holds that once the Rolandic fissure (Rf) has been located, there are distinct differentiated primary motor and sensory functional units confined within a narrow cortical strip: Brodmann's Areas 4 and 6 for primary motor units in front of the Rf and 3, 1, and 2 for sensory units behind the Rf. To test this assumption, we examined in detail the records of cortical mapping done by electrical stimulation of the cerebral cortex via implanted subdural electrode grids in 35 patients with seizure disorders. Of 1381 stimulations of the electrode sites, 346 (25.1%) produced primary motor or motor arrest and sensory responses in contralateral body parts: 56.8% were primary motor responses; 16.2% were motor-arrest; 22.5% were sensory; and the remaining 4.5% were mixed motor and sensory responses. Two-thirds (65.9%) of the primary motor responses were located within 10 mm of the Rf, and the remaining one-third (34.1%) were more than 10 mm anterior to the Rf or were posterior to the Rf. Furthermore, in the patient group with brain lesions, fewer than one-third (28.1%) of the responses were within the 10-mm narrow anterior strip. Our study reconfirmed that a significant number--at least one-third--of motor responses are distributed outside the classic narrow cortical strip. In patients with brain lesions, the motor representation is further displaced outside the narrow strip. This finding indicates that primary motor cortex may extend beyond the gyrus immediately anterior to the Rf. PMID- 1641112 TI - Facial nerve repair by interposition nerve graft: results in 22 patients. AB - Resection of tumors of the posterior cranial base may incorporate a segment of the facial nerve because of tumor infiltration, or may result in unplanned nerve injury. Immediate repair of the facial nerve by resuture or with an autogenous nerve graft is highly desirable to ensure optimal recovery of facial function. Twenty-four patients who underwent extensive surgery of the posterior skull base and facial nerve reconstruction were studied. Of these, 12 patients had preoperative facial weakness and 3 had facial palsy. All patients underwent graft reconstruction from the subarachnoid or labyrinthine portion of the facial nerve to the fallopian or extracranial segment. The greater auricular nerve was used as a graft in 14 patients, and the sural nerve in 10. Two patients died of their disease soon after surgery, and, therefore, were excluded from our follow-up. In the remaining 22 patients, the median follow-up time was 20 months. As evaluated by the House-Brackmann grading system, 45% (10/22) of the surviving patients achieved a good recovery of facial function, 36% (8/22) attained a fair recovery, and 18% (4/22) had minimal or no recovery. There was no statistical correlation between the length of the graft used and the degree or timing of clinical recovery. The surgical result obtained in all patients with complete preoperative facial palsy and in one patient with dense facial paresis was poor. PMID- 1641113 TI - Aggressive oligodendroglioma: a chemosensitive tumor. AB - Aggressive oligodendrogliomas, tumors that are symptomatic, enlarging, enhancing, and usually but not always anaplastic, respond to chemotherapy. We have observed responses to chemotherapy in 18 of 19 consecutively treated patients with newly diagnosed or recurrent aggressive oligodendrogliomas. A regimen of procarbazine, CCNU (lomustine), and vincristine (PCV) is predictably effective, but other drugs have antioligodendroglioma activity. Cooperative group trials will be necessary to determine the most effective drug, or combination of drugs, and to explore fully the role of chemotherapy in the treatment of this uncommon glioma. PMID- 1641114 TI - Cerebrovascular effects and tumor kinetics after a single intratumoral injection of human recombinant interleukin-2 alone or in combination with intravenous chemotherapy in a rat model of glioma. AB - It is well documented that drug delivery into experimental and human brain tumors is limited by the variably intact blood-brain barrier (BBB) at the growing edge. The aim of the present investigation was to examine the histopathological changes that occur after a single intralesional injection of human recombinant interleukin-2 (rIL-2) into a growing glioma and determine whether the injection improved delivery of cytotoxic drug into the neuropil surrounding the site of lymphokine injection. Because an intracerebral injection of rIL-2 causes a temporary breakdown in the BBB, we hoped to enhance drug penetration into peritumoral areas of brain with an intact BBB by using the novel biomodulating effect of rIL-2 on the cerebral endothelial cells. The results demonstrated that an intralesional injection of 7.2 x 10(4) National Units rIL-2 on Day 7 after tumor inoculation did not accentuate the already increased cerebrovascular permeability produced by the glioma nor did rIL-2 trigger additional or aggravate neurological deficits in glioma-bearing rats. Before the administration of chemotherapy in vivo, the RT-2 glioma cells were tested for in vitro sensitivity by colorimetric assay. At 24 hours after exposure to either methotrexate (MTX), vincristine (VIN), or doxorubicin (DOX), no significant inhibition of metabolic activity was observed. In contrast, a timed pulsed of any drug for 5 minutes caused significant dose-dependent inhibition of RT-2 glioma cells at 48 hours to 5 days after drug administration. Animal models receiving an intralesional injection of rIL-2 followed 3 days later by an intravenous dose of 30 mg/kg MTX, 0.23 mg/kg VIN, or 10 mg/kg DOX demonstrated that only MTX combined with intralesional rIL-2 significantly inhibited intracranial proliferation of RT-2 glioma cells. Use of intralesional rIL-2 and intravenous chemotherapy, however, did not significantly increase survival in this animal model of glioma. These results show that the combination of cytotoxic drugs with intralesional rIL-2 can be safely applied in the management of glioma and may form a rational basis for additional pharmacological investigations of a wider assortment of chemotherapies in combination with rIL-2 for intracranial malignancies. PMID- 1641115 TI - Parallel and serial visual search after closed head injury: electrophysiological evidence for perceptual dysfunctions. AB - Event-related potentials (ERPs) were recorded from closed head injury (CHI) patients at least 2 years postinjury and from controls in order to assess their parallel and serial processing abilities during visual search. In Experiment 1, stimuli consisted of arrays of eight triangles; half of the arrays contained a target item. In the "feature-present" condition, the target item was a triangle with an additional horizontal line that could be detected automatically and in parallel, while in the "feature-absent" condition all items except for the target triangle had an additional horizontal line, thus requiring a serial search. In Experiment 2, stimuli consisted of eight solid bars (50%), seven solid bars and a vertical open bar (25%), and seven solid bars and a horizontal open bar (25%): the array containing the horizontal bar served as a target. By recording ERPs to the arrays containing vertical open bars, which were similar to the target items, parallel processing of "pop-out" stimuli could be studied in the absence of any overt response. ERP data were compared with the results of neuropsychological and neuroimaging (MRI, CAT) examination. Patient exhibited a decreased behavioral performance both in the parallel and in the serial processing mode. Furthermore, abnormalities of early and intermediate ERP components (P1, N1, P2, N2) were found, whereas the late component (P3) was less affected by CHI. The results were interpreted as an index of CHI-induced dysfunctions in perceptual processes such as simple feature registration and early target discrimination. It was suggested that these dysfunctions contribute to impairments of parallel as well as serial processes in visual search. PMID- 1641116 TI - To halve and to halve not: an analysis of line bisection judgements in normal subjects. AB - Normal adults were tested in a series of three experiments to examine the influences of spatial location and cueing upon line bisection judgements. Judgements in all three experiments were strongly influenced by cueing with a letter at one or other end of the line. The spatial location of the line (in left, central or right body space) also had a minor effect in Experiments 1 and 2, where evidence was additionally found for a small constant error when lines were presented centrally. It is argued from the results of Experiments 2 and 3, where no explicit bisection response was required, that perceptual/attentional factors, rather than an orienting bias, play the major role in mediating the cueing effect. It is concluded that there is a substantial attentional effect upon judgements of extent, whereby paying less attention decreases perceived relative line length. However the constant error and the effect of spatial location, whilst mainly perceptual in nature, may also be partly determined by premotor orienting biases caused by differential hemispheric activation. PMID- 1641117 TI - The computation of perceptual structure from collinearity and closure: normality and pathology. AB - Three experiments tested how structural information affects the processing of fragmented forms, using evidence from both normal subjects and an agnosic patient. The stimuli were either (a) outline drawings of objects; (b) "well" or "poorly" structured fragmented forms derived from outline drawings (Experiments 1 and 2) or (c) "well" or "poorly" structured fragmented forms derived from outline drawings of meaningless forms (Experiment 3). "Well" and "poorly" structured forms varied on the properties of collinearity and closure of the elements. Subjects decided if two simultaneously presented forms had the same orientation or were mirror-reversed. Three levels of discriminability were examined: (a) for "symmetrical" forms the decision had to be based on the detection of a small feature appearing on the same or the opposite side in the two forms; (b) for "asymmetrical" forms the decision had to be based on a large part located on the same or the opposite side of each object; and (c) for "oblique" forms, matching could be based on the global orientation of the shapes. Normal subjects performed equivalently on outline drawings and "well" structured fragmented forms and worse on "poorly" structured forms. This effect was strongest on "asymmetrical" stimuli, both with meaningful (Experiments 1 and 2) and meaningless forms (Experiment 3). This indicates that the segmentation of forms into parts, for judgements with "asymmetrical" stimuli, is affected by the structural properties of collinearity and closure. For the agnosic patient, performance was similar for "well" and "poorly" structured forms, and there was better performance in the "oblique" condition. This suggests that the patient could use global shape information, but that this coexists with a selective deficit in computing local perceptual structure, based on collinearity and closure between form elements. The implications of the results for understanding form perception and the clinical use of fragmented forms, are discussed. PMID- 1641118 TI - Ocular exploration in the dark by patients with visual neglect. AB - Eye-movements were recorded as patients with visual neglect searched in a completely darkened room to determine whether any light was present. Fixations were confined almost entirely to the right of the midline, and biased rightwards within that area. A control group with visual field defects searched equally to both sides. This shows that neglect patients have a bias to look to the right which is independent of the difficulty they also have in processing sensory information in the left visual field. Results are related to theories of the hemispheric control of attention and to the view that the representation of contralateral space is impaired in neglect. PMID- 1641119 TI - Spatio-motor cueing in unilateral left neglect: the role of hemispace, hand and motor activation. AB - Reported beneficial effects of left arm activation on neglect are experimentally examined. The present study of a subject with left visual neglect compared left hand finger movement with an instruction to visually anchor perception on the left arm during letter cancellation. Only the finger movements significantly reduced neglect. Another comparison was between "out of sight" finger movements of the left hand in left and right hemispace, respectively. Only left hemispace "blind" finger movements significantly reduced neglect compared to the standard condition. Thirdly, blind left finger movements in left hemispace were compared with passive visual cueing (reading a changing number) and again it was found that only the finger movements reduced neglect. Finally, right finger movements in left hemispace were compared with left finger movements in left hemispace: only the latter reduced neglect. The implications of these findings for theory and therapy of neglect are discussed. PMID- 1641120 TI - Different mental imagery abilities result in different regional cerebral blood flow activation patterns during cognitive tasks. AB - Using regional cerebral blood flow (rCBF) imaging, two populations having high and low imagery abilities were compared at rest and while performing two cognitive tasks: silent verb conjugation and mental imagery. The imagery task produced an rCBF increase in the left visual association and left frontal cortices in both groups. Differences between high and low imagers were observed on global and regional flow responses to cognitive tasks: low imagers showed a whole cortex CBF increase during both tasks; high imagers showed a right dominance in the visual association cortex in all conditions, and in the parietal association cortex at rest. PMID- 1641121 TI - Regional cerebral blood flow patterns related to verification of low- and high imagery sentences. AB - Although several SPECT studies have shown left inferior occipital activation with visual imagery, the reliability of this finding remains doubtful. The present study replicated two conditions of a previous SPECT-study exploring rCBF in subjects verifying the correctness of low- and high-imagery sentences. As in the previous study, verification of high-imagery sentences was associated with higher flow rates in the left inferior occipital region and lower flow rates in the right anterior frontal region. By contrast, a bilateral increase of thalamic flow rates with imagery was not replicated, and there was a higher flow rate in the left inferior temporal region with low-imagery sentences which had not been found in the original study. PMID- 1641122 TI - Abnormal eye movement behaviour during text reading in neglect syndrome: a case study. AB - The eye movement behaviour of a patient suffering from a right basal ganglia infarction with a left-sided hemineglect but without any visual field defects was investigated during reading. The eye movements were registered by means of an i.r. light technique (pupil-corneal reflection method). The main findings were abnormal return sweeps. Whereas in normal readers the end of one line of text is linked to the beginning of the new line by a long leftward saccade, the return sweeps of the hemineglect patient stereotypically ended in the middle of the next line. They were followed by sequences of short saccades indicating silent backward reading until a linguistically plausible continuation of sentences from the previous line was found, irrespective of the actual beginning of text. The shortened return sweeps could not be attributed to a general oculomotor disturbance. The spatial border for the occurrence of the patient's abnormal scanning pattern (left half of texts) clearly did not depend on a retinal coordinate frame of reference but rather has to be attributed to a different body centred reference system. PMID- 1641123 TI - A specific form of cognitive rigidity following excitotoxic lesions of the basal forebrain in marmosets. AB - The effects of N-methyl-D-aspartate-induced lesions of the basal forebrain were studied on performance of a series of visual discrimination tests that examined a range of cognitive functions in the marmoset. These included the ability to attend to the various dimensional properties of stimuli and to use just one of these properties in order to solve a discrimination (intra-dimensional shift); to switch attention from one dimension to another (extra-dimensional shift); to learn the reinforcement value of specific exemplars within a dimension (new learning); and to relearn their reinforcement value following reversal of the reward contingencies (serial reversals). Lesions of the basal forebrain did not impair the ability either to attend selectively to the dimensional properties of the stimuli or to switch attention from one dimension to the other. However, the lesion did affect various aspects of associative learning including a transient impairment of new learning and a marked disruption of serial reversal learning. The reversal deficit could be characterised as a tendency to perseverate on the previously correct stimulus and as a failure to to show the formation of a reversal learning set. In addition, the lesion prevented disruption of performance of a well-learned discrimination when novel exemplars from the irrelevant dimension were introduced (probe test). It is suggested that the functional effects of the basal forebrain lesion reflect impaired learning of stimulus-reward associations and behavioural rigidity. The finding, however, that there was no effect of the lesion on attentional set-shifting suggests that any loss of inhibitory control was specific to the level of stimulus-response or stimulus-reward associations, inhibitory control at the level of attentional selection remaining intact. The similarity of the effects of damage to the basal forebrain to those seen following damage to the orbitofrontal cortex and the amygdala are discussed in the context of the close anatomical and functional relationships that exist among these three structures. PMID- 1641124 TI - Various types of inhibitory postsynaptic potentials in anterior thalamic cells are differentially altered by stimulation of laterodorsal tegmental cholinergic nucleus. AB - The effects of stimulating the laterodorsal tegmental cholinergic nucleus upon inhibitory postsynaptic potentials recorded in relay cells of the anterior thalamic complex were studied in urethane-anesthetized cats. The inhibitory postsynaptic potentials induced in anterior thalamic relay cells by stimulating mammillary nuclei or retrosplenial cortex are generated by local-circuit inhibitory neurons since this nuclear complex is devoid of afferents from the other intrathalamic source of inhibition, the reticular thalamic nucleus. In a parallel study from this laboratory, it has been shown that cortical stimulation elicits a biphasic inhibitory postsynaptic potential consisting of two (A and B) components attributed to axonal firing of local interneurons, whereas mammillary stimulation elicits, in addition to the A-B sequence, an earlier component (a) presumably generated by presynaptic dendrites in thalamic glomeruli. In the present study, short pulse-trains applied to the laterodorsal tegmental nucleus diminished the amplitudes of A and B inhibitory components or completely suppressed them. The B component was more sensitive to the depressive effect. By contrast with the changes of the A and B components, the mammillary-evoked a inhibitory component was not reduced and, in many instances, was enhanced following laterodorsal tegmental stimulation. The effects of laterodorsal tegmental stimulation survived monoamine depletion by reserpine. We suggest that mesopontine cholinergic depressive actions on A and B inhibitory postsynaptic potentials may be due to an increased conductance in thalamocortical cells during the short-lasting nicotinic action combined with a somatic hyperpolarization of local-circuit cells, whereas the enhancement of the earliest (a) inhibitory postsynaptic potential reflects a concomitant potentiating action at the level of intraglomerular presynaptic dendrites. PMID- 1641125 TI - Regionally specific and rapid increases in brain-derived neurotrophic factor messenger RNA in the adult rat brain following seizures induced by systemic administration of kainic acid. AB - In situ hybridization techniques were used to analyse the spatiotemporal pattern of brain-derived neurotrophic factor messenger RNA elevation associated with kainic acid-induced seizure activity in the rat. Pronounced increases in hippocampal brain-derived neurotrophic factor messenger RNA levels were observed as early as 30 min following the onset of behavioral seizures. The greatest increase (10-fold) occurred in the dentate granule cell layer, while pyramidal layers CA1, CA3, and CA4 exhibited increases of two- to six-fold. Peak elevation of brain-derived neurotrophic factor messenger RNA in CA1 hippocampal region was evident at 4 h in CA3, and in the dentate granule layer at 30 min postseizure. Elevations persisted in the dentate and hilar regions to four days, while the increases in CA1 and CA3 returned to control levels by 16 h following seizure. Significant increases in brain-derived neurotrophic factor messenger RNA were also observed in the superficial layers of cortex (II and III) and in the piriform cortex which reached peak elevations by 8 h. No detectable changes were observed in the dorsomedial thalamus. Although histologically defined pyramidal and granule cell layers displayed relatively uniform increases in brain-derived neurotrophic factor messenger RNA in response to kainate, a closer examination of the labeling patterns using emulsion autoradiography revealed discrete areas of high grain densities overlapping uniform, moderate hybridization densities in the dentate granule cell layer and CA3, suggesting that the capacity to upregulate brain-derived neurotrophic factor messenger RNA in these regions may differ among individual neurons. In conclusion, our studies revealed that brain-derived neurotrophic factor messenger RNA induction in response to systemic kainate administration differs in hippocampal and cortical areas, in magnitude, time of onset and duration. The observed temperospatial pattern does not correspond in a simple way to increases in metabolic or electrical activity associated with seizures or neuronal vulnerability coincident with the seizures. PMID- 1641126 TI - Pertussis toxin administration increases the expression of proneurotensin and preproenkephalin A mRNAs in rat striatum. AB - The effect of a unilateral intrastriatal microinjection of pertussis toxin on the expression of proneurotensin and preproenkephalin A mRNAs in the adult rat neostriatum was investigated using a technique of non-radioactive in situ hybridization. Control sham microinjected animals received an equal volume of vehicle only and were processed in parallel with the pertussis toxin-treated rats. All rats were allowed to recover from the stereotaxic surgery for 22 h before being killed and their brains rapidly removed and processed for in situ hybridization using alkaline phosphatase-labelled oligonucleotide probes. In comparison to sham microinjected rats, a single intrastriatal microinjection of pertussis toxin (1 microgram) resulted in a significant increase in the amount of both proneurotensin and preproenkephalin A mRNAs in the ipsilateral neostriatum. For proneurotensin mRNA, this increase was reflected by a substantial increase in the number of mRNA-containing cells detected. Proneurotensin mRNA-containing cells detected in the nucleus accumbens appeared to be unaffected by the intrastriatal pertussis toxin microinjection. In contrast, the significant increase in preproenkephalin A mRNA, when compared to the contralateral uninjected striatum and the ipsilateral striatum of control sham injected rats, was reflected by an increase in the cellular amount of preproenkephalin A mRNA and not by an increase in the number of mRNA-containing cells detected. These results demonstrate that the expression of both proneurotensin mRNA and preproenkephalin A mRNA in the adult rat striatum are rapidly increased in vivo by an intrastriatal microinjection of pertussis toxin. PMID- 1641127 TI - Muscarinic antagonists attenuate neurotensin-stimulated accumbens and striatal dopamine metabolism. AB - The effect of scopolamine and atropine upon the increase in extracellular 3,4 dihydroxyphenylacetic acid induced by central injection of neurotensin was examined in the nucleus accumbens and the striatum of anaesthetized rats using in vivo differential pulse voltammetry with carbon fibre electrodes. Scopolamine (1 and 3 mg/kg, i.p.) and atropine (20 micrograms, i.c.v.) did not alter the 3,4 dihydroxyphenylacetic acid level in the nucleus accumbens or the striatum, measured for 60 min after administration. Neurotensin (10 micrograms, i.c.v.) increased the 3,4-dihydroxyphenylacetic acid peak height in both regions. Pretreatment with scopolamine (1 mg/kg) 15 min before neurotensin injection blocked the increase in extracellular 3,4-dihydroxyphenylacetic acid in the striatum but not in the nucleus accumbens whilst scopolamine (3 mg/kg) partially attenuated the effect of neurotensin in the nucleus accumbens and blocked the increase in 3,4-dihydroxyphenylacetic acid in the striatum. Atropine partially attenuated the effect produced by neurotensin in the nucleus accumbens and blocked the increase in 3,4-dihydroxyphenylacetic acid induced by the peptide in the striatum. However, the increase in extracellular 3,4-dihydroxyphenylacetic acid induced by haloperidol (1 mg/kg, s.c.) was not altered by scopolamine (1 mg/kg) or atropine. Also, the increase in dopamine metabolism in the nucleus accumbens and the striatum after centrally injected haloperidol (10 micrograms, i.c.v.) was not altered by atropine (20 micrograms, i.c.v.). Together, the results demonstrate a functional interaction between muscarinic antagonists and neurotensin on in vivo dopamine metabolism in the nucleus accumbens and the striatum but with a greater effect in the latter region. PMID- 1641128 TI - Virtual trajectories of single-joint movements performed under two basic strategies. AB - The framework of the equilibrium point hypothesis has been used to analyse motor control processes for single-joint movements. Virtual trajectories and joint stiffness were reconstructed for different movement speeds and distances when subjects were instructed either to move "as fast as possible" or to intentionally vary movement speed. These instructions are assumed to be associated with similar or different rates of change of hypothetical central control variables (corresponding to the speed-sensitive and speed-insensitive strategies). The subjects were trained to perform relatively slow, moderately fast and very fast (nominal movement times 800, 400 and 250 ms) single-joint elbow flexion movements against a constant extending torque bias. They were instructed to reproduce the motor command for a series of movements while ignoring possible changes in the external torque which could slowly and unpredictably increase, decrease, or remain constant. The total muscle torque was calculated as a sum of external and inertial components. Fast movements over different distances were made with the speed-insensitive strategy. They were characterized by an increase in joint stiffness near the midpoint of the movements which was relatively independent of movement amplitude. Their virtual trajectories had a non-monotonic N-shape. All three arms of the N-shape scaled with movement amplitude. Movements over one distance at different speeds were made with a speed-sensitive strategy. They demonstrated different patterns of virtual trajectories and joint stiffness that depended on movement speed. The N-shape became less apparent for moderately fast movements and virtually disappeared for the slow movements. Slow movements showed no visible increase in joint stiffness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641129 TI - Muscarinic M2 receptor mRNA expression and receptor binding in cholinergic and non-cholinergic cells in the rat brain: a correlative study using in situ hybridization histochemistry and receptor autoradiography. AB - The goal of the present study was to identify the cells containing mRNA coding for the m2 subtype of muscarinic cholinergic receptors in the rat brain. In situ hybridization histochemistry was used, with oligonucleotides as hybridization probes. The distribution of cholinergic cells was examined in consecutive sections with probes complementary to choline acetyltransferase mRNA. Furthermore, the microscopic distribution of muscarinic cholinergic binding sites was examined with a non-selective ligand ([3H]N-methylscopolamine) and with ligands proposed to be M1-selective ([3H]pirenzepine) or M2-selective ([3H]oxotremorine-M). The majority of choline acetyltransferase mRNA-rich (i.e. cholinergic) cell groups (medial septum-diagonal band complex, nucleus basalis, pedunculopontine and laterodorsal tegmental nuclei, nucleus parabigeminalis, several motor nuclei of the brainstem, motoneurons of the spinal cord), also contained m2 mRNA, strongly suggesting that at least a fraction of these receptors may be presynaptic autoreceptors. A few groups of cholinergic cells were an exception to this fact: the medial habenula and some cranial nerve nuclei (principal oculomotor, trochlear, abducens, dorsal motor nucleus of the vagus). Furthermore, m2 mRNA was not restricted to cholinergic cells but was also present in many other cells throughout the rat brain. The distribution of m2 mRNA was in good, although not complete, agreement with that of binding sites for the M2 preferential agonist [3H]oxotremorine-M, but not with [3H]pirenzepine binding sites. Regions where the presence of [3H]oxotremorine-M binding sites was not correlated with that of m2 mRNA are the caudate-putamen, nucleus accumbens, olfactory tubercle and islands of Calleja. The present results strongly suggest that the M2 receptor is expressed by a majority of cholinergic cells, where it probably plays a role as autoreceptor. However, many non-cholinergic neurons also express this receptor, which would be, presumably, postsynaptically located. Finally, comparison between the distribution of m2 mRNA and that of the proposed M2-selective ligand [3H]oxotremorine-M indicates that this ligand, in addition to M2 receptors, may also recognize in certain brain areas other muscarinic receptor populations, particularly M4. PMID- 1641130 TI - Evidence of GABA-immunopositive neurons in the dorsal part of the lateral geniculate nucleus of reptiles: morphological correlates with interneurons. AB - The distribution and staining pattern of gamma-aminobutyric acid immunoreactivity have been examined by both light and electron microscopy in the dorsal part of the lateral geniculate nucleus of three reptilian species: the turtle Chinemys reevesi, the lizard Ophisaurus apodus and the snake Vipera aspis. After perfusion of the animals with 1% paraformaldehyde and 1% glutaraldehyde and polyethyleneglycol embedding of the brains, the analysis of sections processed immunocytochemically with an anti-GABA antiserum has revealed a moderate-to-dense labeling of the neurons of the dorsal part of the lateral geniculate complex in these species. Labeled cell bodies are small-sized, either rounded or fusiform and the GABA-positive dendrites emerging from them are not preferentially oriented in any particular direction. Quantitative studies in Vipera indicate that GABA-positive neurons make up about 14% of the population of neurons of the dorsal part of the lateral geniculate nucleus. Electron microscopy of specimens treated by either pre- or post-embedding techniques has confirmed that these cells corresponded to neurons. No glial cells were ever observed to be immunopositive. These GABA-positive neurons, characterized by the presence of pleiomorphic synaptic vesicles localized either in their perikaryon or more often in presynaptic dendrites, established symmetrical synaptic contacts. In this case, the latter were involved both pre- and postsynaptically in serial and, more rarely, in triadic arrangements, a synaptic organization specific to interneurons. The involvement of such GABA-positive neurons in local circuits is discussed. PMID- 1641131 TI - A new monoclonal antibody against the GABA-protein conjugate shows immunoreactivity in sensory neurons of the rat. AB - A monoclonal antibody, 115AD5, was raised against GABA coupled to bovine serum albumin. The monoclonal antibody 115AD5 also reacted with other GABA-protein conjugates. The specificity of the monoclonal antibody was corroborated by enzyme linked immunoassay, dot-immunobinding experiments and immunostaining of rat cerebellum sections. The monoclonal antibody 115AD5 could successfully be applied on Vibratome and cryostat sections using either indirect immunofluorescence or peroxidase techniques. In rat cerebellar cortex the monoclonal antibody 115AD5 gave an intense immunoreaction in stellate cells, in Golgi neurons, and in basket cells and their processes around Purkinje cell bodies. Purkinje cell dendrites showed GABA immunoreactivity while the cell bodies were non-reactive or only weakly reactive. There was labelling in some nuclei of Purkinje cells. GABA immunoreactivity was also found in dot-like structures in the granular layer. A large population of sensory neurons in rat thoracic and lumbar spinal dorsal root ganglia presented an intense immunoreactivity for the monoclonal antibody 115AD5. Nerve bundles immunoreactive for GABA were also seen in these ganglia. In the trigeminal ganglion, a major population of sensory neurons and some of their processes presented immunoreactivity for GABA. In the sensory nodose ganglion of the vagus nerve, many neuronal cell bodies and some fibres were immunoreactive for GABA. Ligation of the vagus nerve caudal to the ganglion resulted in an increased GABA immunoreactivity in neuronal somata of the ganglion, as well as in nerve fibres on the ganglionic side of the ligature. The present results suggest that in the rat, a population of sensory neurons in thoracic and lumbar spinal dorsal root ganglia, as well as in the trigeminal and nodose ganglia contain GABA. The presence of GABA immunoreactivity in these neurons raises the possibility of a neurotransmitter or modulator role. PMID- 1641132 TI - Oxytocin-containing pathway to the bed nuclei of the stria terminalis of the lactating rat brain: immunocytochemical and in vitro electrophysiological evidence. AB - Immunocytochemical staining within the forebrain of lactating rats revealed oxytocin-immunoreactive perikarya in a continuum running from the anterior parvocellular hypothalamic paraventricular nucleus through the anterior commissural nucleus and perifornical region. Beaded axons could be seen arising from these perikarya to enter the bed nuclei of the stria terminalis. In sections cut at a 45 degree angle to the parasagittal plane, much of this pathway could be maintained intact, and in vitro tissue slices prepared in this orientation were used for electrophysiological studies of oxytocinergic innervation of the bed nuclei. By extracellular recording, neurons of the bed nuclei of the stria terminalis were tested for their response to exogenous oxytocin and to stimulation of the paraventricular hypothalamus. Both short latency (3-40 ms) orthodromic excitation (26/78 neurons) and longer latency (greater than 100 ms) excitation (12/78 neurons) were observed following paraventricular hypothalamic stimulation, possibly representing mono- and polysynaptic inputs, respectively. Removal of extracellular Ca2+ blocked these orthodromic responses (n = 6). Antidromic invasion was seen in a further 11/78 neurons with characteristics of constant latency (mean = 5.9 +/- 0.7 ms), high frequency following (40-80 Hz) and persistence in Ca(2+)-free medium. When tested for the effect of oxytocin (10(-7) M), none (0/11) of the antidromically activated neurons were excited, but nine of 34 of the orthodromically excited neurons (both short and long latency) responded with a marked increase in activity. In three of eight cases, the orthodromic synaptic excitation following hypothalamic stimulation could be reversibly attenuated by the receptor antagonist [d(CH2)5,D-Tyr(OEt)2,Val4,Cit8]-vasopressin (0.5 or 2.5 x 10(-6) M), further substantiating the involvement of oxytocin. These data provide anatomical and electrophysiological evidence for an oxytocinergic innervation of the bed nuclei of the stria terminalis. This pathway is discussed in terms of possible involvement in mediating the facilitatory effect of oxytocin on the milk-ejection reflex of lactating rats which has been suggested to act through this part of the limbic system. PMID- 1641133 TI - Interleukin-1 alpha expression is inducible by cholinergic stimulation in the rat adrenal gland. AB - Interleukin-1-like immunoreactivity has earlier been demonstrated by immunohistochemistry in the noradrenaline-containing chromaffin cells of the rat adrenal gland [Schultzberg et al. (1989) Neuroscience 30, 805-810; Schultzberg et al. (1987) J. Neurosci. Res. 18, 184-189]. In this study, we examine the regulation, upon cholinergic stimulation, of the expression of the cytokine interleukin-1 alpha in the rat adrenal gland. Interleukin-1 alpha and interleukin 1 alpha mRNA levels in the adrenal gland are affected by systemic administration of the cholinergic agonists nicotine (0.5 mg/kg, i.p.) and carbachol (0.5 mg/kg, i.p.). Both drugs cause an increase in interleukin-1 alpha mRNA levels. In contrast to the increased mRNA levels, nicotine and carbachol reduce the interleukin-1 alpha protein level measured in the rat adrenal gland: nicotine by approximately 30%, 60 min after injection, and carbachol by approximately 55%, 30 min after injection. The interleukin-1 alpha protein level returns to control level 90 min after nicotine injection, and 120 min after carbachol injection. We thus found a large, constitutively expressed and inducible pool of interleukin-1 alpha in the rat adrenal gland, which appears to be sensitive to cholinergic stimulation and which may be responsible for some of the local and systemic effects of interleukin-1 alpha. Experiments with Escherichia coli lipopolysaccharide show that this substance, which induces interleukin-1 expression and secretion in macrophages, is also able to induce the expression of interleukin-1 alpha mRNA and interleukin-1 alpha in the adrenal gland when injected at the dose of 2 mg/kg, i.p. PMID- 1641134 TI - Exercise therapy for positional vertigo. AB - We present a common cause of vertigo, benign positional paroxysmal vertigo (BPPV), and its history, diagnosis, and therapy. BPPV is suggested by history, readily diagnosed by office examination, and cured by appropriate exercise therapy. Since the condition is so common and often unrecognized, physicians are encouraged to consider BPPV as a possible cause of treatable dizziness. PMID- 1641135 TI - Parkinson's disease in twins. AB - Among nine monozygotic (MZ) and 12 dizygotic (DZ) twin pairs in which an index case had typical Parkinson's disease (PD) or PD with associated dementia, three MZ and three DZ pairs were concordant. Three of the six affected co-twins were first diagnosed during the study. Occurrence of PD in families of MZ and DZ index cases was more frequent than expected from population rates. The study underlines the need for personal examination using defined criteria in a cross-sectional twin study on PD. Although the study did not establish a major genetic impact in the etiology of PD, a genetic predisposition for the disease cannot be ruled out for some individuals. PMID- 1641136 TI - Asymmetric cortical degenerative syndromes: clinical and radiologic correlations. AB - Eight patients presented with slowly progressive focal neurologic syndromes that conformed to one of three clinically defined categories: progressive nonfluent aphasia (three patients), progressive perceptual-motor impairment (four patients), and progressive frontal lobe syndrome (one patient). Planar MRI and MRI-based surface or volume renderings demonstrated focal areas of atrophy that correlated well with clinical deficits. Single-photon emission computed tomography (SPECT) showed areas of cortical hypoperfusion that corresponded to focally atrophic regions revealed by MRI, but abnormal areas with SPECT were larger than those suggested by MRI. MRI and SPECT are useful in defining the regional structural and functional cerebral abnormalities that underlie slowly progressive focal neurologic syndromes caused by asymmetric cortical degeneration. PMID- 1641137 TI - A double-blind, randomized, crossover trial of pemoline in fatigue associated with multiple sclerosis. AB - Fatigue occurs in a majority of patients with MS and is generally independent of measurable neurologic disability. Few options for treatment are available. We conducted a double-blind, placebo-controlled, crossover trial for each of two 4 week treatment periods. Forty-six eligible patients entered and five dropped out due to concurrent exacerbations. Nineteen patients (46.3%) experienced excellent or good relief of fatigue with pemoline, and eight patients (19.5%) with placebo (p = 0.06, Fisher's exact test). One-fourth of patients did not tolerate the drug well, and 7% had to discontinue pemoline during the study due to side effects. The most common side effects were anorexia, irritability, and insomnia. Pemoline may be an effective short-term treatment for fatigue associated with MS, but its adverse effects are not well tolerated by many patients. PMID- 1641138 TI - Epidemiology of human immunodeficiency virus encephalopathy in the United States. AB - To investigate the epidemiology of human immunodeficiency virus (HIV) encephalopathy, we analyzed cases of acquired immunodeficiency syndrome (AIDS) reported to the Centers for Disease Control (CDC) from September 1, 1987, through August 31, 1991. Of 144,184 persons with AIDS (PWAs), 10,553 (7.3%) were reported to have HIV encephalopathy. The proportion of PWAs with HIV encephalopathy was highest at the extremes of age: in PWAs less than 15 years old the proportion was 13%, and in PWAs greater than or equal to 15 years old the proportion progressively increased with age, from 6% in PWAs 15 to 34 years old to 19% in PWAs greater than or equal to 75 years old (p = 0.00001, chi 2 test for linear trend in proportions). The reported annual incidence of HIV encephalopathy per 100,000 population aged 20 to 59 years was 1.4 in 1988, 1.5 in 1989, and 1.9 in 1990. This analysis best provides estimates for HIV encephalopathy as the initial manifestation of AIDS because the CDC AIDS reporting system often does not ascertain diagnoses after the initial AIDS report. These data suggest that age (very young or old) is associated with the development of HIV encephalopathy and that HIV encephalopathy is a common cause of dementia in adults less than 60 years old in the United States. PMID- 1641139 TI - Adult-onset motor neuron disease and infantile Werdnig-Hoffmann disease (spinal muscular atrophy type 1) in the same family. AB - We describe a family in which infantile Werdnig-Hoffmann disease and adult-onset progressive muscular atrophy both occurred. The possibility of these two diseases developing within the same family by chance is unlikely, and several genetic hypotheses may be put forward to explain the association. We suggest that the molecular pathogenesis of these two subtypes of lower motor neuron degeneration may be linked. The genetic defect in the childhood spinal muscular atrophies has been mapped to chromosome 5q in close proximity to the microtubule-associated protein 1B locus. The association of diseases within this family suggests that chromosome 5q should also be studied in relation to adult-onset familial motor neuron disease. PMID- 1641140 TI - A case-control study of Alzheimer's disease in China. AB - We conducted a case-control study to assess possible factors associated with Alzheimer's disease (AD) with 70 clinically diagnosed AD patients and 140 age- and sex-matched nondemented neighborhood controls in China. Factors significantly associated with AD cases were family history of dementia in first-degree relatives, family history of psychotic disorders in first-degree relatives, and left-handedness/ambidexterity. A history of arthritis showed a significantly negative association with AD. Neither a family history for Down's syndrome, history of head trauma, nor other conditions that might support immune or viral hypotheses in AD were significantly associated with AD cases. These data support the role of familial/genetic factors in AD. PMID- 1641141 TI - Intrafamilial heterogeneity in hereditary motor neuron disease. AB - Although there are varied inheritance patterns in motor neuron disease (MND), the phenotype of MND is reported to be constant within these families, ie, cases of amyotrophic lateral sclerosis or primary lateral sclerosis do not occur in pedigrees with cases of spinal muscular atrophy. We describe four pedigrees whose members diverged in the phenotype of MND expressed. The intrafamilial variation of phenotype suggests a similar pathogenesis for some of the varied types of familial MND and the need for careful inquiry of family history in all patients with MND. PMID- 1641142 TI - Cognitive planning deficit in patients with cerebellar atrophy. AB - We compared the performance of 12 patients with cerebellar atrophy (CA) and 12 normal controls matched for age and education on the Tower of Hanoi, a nine problem task that requires cognitive planning. CA patients performed significantly worse than controls on this task despite no difference in planning and between-move pause times. A reanalysis of the data using just the subgroup of patients with pure cerebellar cortical atrophy (CCA) (N = 9) replicated the above results and also showed that CCA patients had significantly increased planning times compared with controls. Neither age, sex, education level, severity of dementia, word fluency, response time, memory, nor visuomotor procedural learning predicted CA or CCA performance. This deficit in cognitive planning suggests a functional link between the cerebellum, basal ganglia, and the frontal lobe concerning specific cognitive processes. However, the exact role of the cerebellum in cognitive planning remains undetermined. PMID- 1641143 TI - Cerebrovascular complications of bacterial meningitis in adults. AB - We performed a prospective study of the type, frequency, temporal profile, and prognostic role of cerebrovascular complications in 86 adults with bacterial meningitis. Cerebral angiography was performed in 27 patients (31.4%) who had focal deficits either clinically, on cranial CT, or both, and in patients who had persistent coma without explained cause despite 3 days of antibiotic therapy. Alterations of the vessel systems, including involvement of major arteries at the base of the brain, medium-sized arteries, small vessels, and major sinuses and cortical veins, were present in 13 of the 27 patients who had angiography. Typical cerebrovascular complications were arterial narrowing of the supraclinoid portion of the internal carotid artery; vessel wall irregularities, focal dilatations, and occlusions of distal branches of the middle cerebral artery; focal abnormal parenchymal blush; and thrombosis of the sagittal superior sinus and cortical veins. Prognosis for those patients with cerebrovascular complications was unfavorable. Six patients died, one remained in a vegetative state, four were moderately or slightly disabled, and only two recovered completely. The study showed that angiographically documented cerebrovascular complications are the most frequent intracranial complications in bacterial meningitis of the adult (37.1%) and are major determinants in the prognosis of this disease. PMID- 1641144 TI - Embolism from vertebral artery origin occlusive disease. AB - We report 10 patients with severe occlusive disease of the vertebral artery (VA) origin in the neck with intra-arterial embolism to the posterior circulation. The VA lesions in seven patients were complete occlusions, and three patients had severe atherostenosis. All patients had strokes in the vertebrobasilar territory. The most frequent recipient sites of intra-arterial embolism were the intracranial VA-posterior inferior cerebellar artery region (8), and the distal basilar artery (BA) and its superior cerebellar and posterior cerebral artery branches (7). Two patients had pontine infarction due to BA embolism. The most common clinical signs were due to cerebellar infarction. Atherosclerotic disease of the VA origin has features in common with disease of the internal carotid artery origin. Both have similar risk factors and demography, and each can cause strokes by intracranial intra-arterial embolism. PMID- 1641145 TI - Characteristics of intractable seizures following meningitis and encephalitis. AB - We studied clinical seizure characteristics, seizure localization, and pathology in 38 patients who developed medically intractable partial seizures following meningitis (n = 16) or encephalitis (n = 22) and were evaluated for epilepsy surgery. Whereas meningitis in this group was commonly associated with mesial temporal sclerosis (MTS), most encephalitis patients had neocortical foci. The age of onset of the encephalitic illness was important in predicting mesial temporal or neocortical foci in that group: encephalitis before, but not after, age 4 years was associated with MTS. Since almost all meningitis occurred before age 4 years, these data support the hypothesis that the medial temporal lobe is particularly susceptible to early insults, establishing the initial pathologic entity of MTS and the subsequent cascade of partial seizures. Later-onset encephalitis produced extrahippocampal neocortical seizure foci, was rarely associated with MRI abnormality, and was difficult to localize precisely. In contrast, meningitis was commonly associated with MTS, aiding seizure localization and successful surgical intervention when seizures were medically uncontrolled. PMID- 1641146 TI - Headache in type I Chiari malformation. AB - We analyzed the headaches in 50 patients with type I Chiari malformation. Of the 50, 14 (28%) had a rather specific, usually protracted, suboccipital-occipital headache of variable quality and duration that was aggravated by Valsalva's maneuver, effort, cough, or postural changes and relieved by occipital suboccipital craniectomy. Only the degree of tonsillar herniation significantly correlated with the presence of this pain. Both migraine and tension-type headache occurred with the expected frequency for the general population. PMID- 1641147 TI - Pendular pseudonystagmus arising as a combination of head tremor and vestibular failure. AB - We describe three patients with spontaneous pendular oscillation of the eye during funduscopy. All patients had blurred, shimmering vision or oscillopsia, exacerbated by concentration, reading, or trivial head movements, and had a history of unsteadiness. Examination revealed a fine head tremor, mild unsteadiness, absent vestibulo-ocular reflex (VOR), and otherwise normal neurologic and ocular motor findings. Rigid immobilization of the head abolished the retinal oscillations. Simultaneous precision recordings of head and eye movements showed that the eye movement was in the compensatory direction to the head tremor but that, in contrast to normal VOR, it was in phase error. We conclude that the essential head tremor was provoking oscillopsia and retinal oscillation because of the absence of VOR. Recognizing the association of head tremor with absent VOR is important since in all these patients the presence of this pendular pseudonystagmus on ophthalmoscopy raised the diagnostic possibility of brainstem disease. PMID- 1641148 TI - Elevated plasma glucagon in amyotrophic lateral sclerosis. AB - This study shown an abnormality in glucagon levels that may explain the glucose intolerance, abnormal insulin reactions, and abnormal plasma amino acid levels seen in amyotrophic lateral sclerosis (ALS). We randomly administered two test meals, differing only in protein source (soy versus casein) at least 1 week apart and measured fasting and postprandial bloods for glucagon, insulin, and glucose levels in 11 ALS patients. With the soy test meal, glucagon levels were elevated in all ALS patients compared with controls: at fasting (237 +/- 111 versus 108 +/ 46 pg/ml, p less than 0.01) and 1/2 hour (389 +/- 94 versus 133 +/- 68 pg/ml, p less than 0.001), and 2 hours postprandial (379 +/- 75 versus 108 +/- 53 pg/ml, p less than 0.001). Glucagon levels after the casein test meal were also significantly elevated. Insulin was elevated by both test meals. Casein produced significant glucose intolerance. PMID- 1641149 TI - Amyotrophic lateral sclerosis: increased solubility of skin collagen. AB - We studied the solubility of skin collagen from six patients with amyotrophic lateral sclerosis (ALS) and six controls. The amount of collagen extracted with neutral salt solution was significantly greater in patients with ALS than in controls. In addition, there was a statistically significant increase in the proportion of collagen extracted from ALS patients with increased duration of illness. The collagen solubilized by pepsin and cyanogen bromide treatments was significantly higher in ALS patients than in controls, and its proportion was positively and significantly associated with duration of illness in ALS patients. These results indicate that the metabolism of skin collagen may be affected in the disease process of ALS, causing an increase in immature soluble collagen in the tissue, which is the opposite to that which occurs in the normal aging process. PMID- 1641150 TI - Positron emission tomography demonstrates frontal cortex and basal ganglia hypometabolism in dystonia. AB - We studied 15 dystonic patients with positron emission tomography (PET) and (18F) 2-fluoro-2-deoxy-D-glucose (FDG). The group comprised patients with focal (n = 5), multifocal (n = 1), and generalized (n = 4) dystonia as well as patients with hemidystonia (n = 5). The age at onset was during childhood in four, during adolescence in two, and during adulthood in nine of the subjects. In dystonic patients, global cerebral glucose metabolism was unaltered when compared with normal controls, whereas the pattern of regional cerebral metabolic rate for glucose (rCMR[Glu]) was significantly different (p = 0.0001). rCMR(Glu) was significantly decreased in the caudate and lentiform nucleus and in the frontal projection field of the mediodorsal thalamic nucleus. The study confirms the concept that dystonia is caused by impaired connections between the basal ganglia, the thalamus, and frontal association areas. PMID- 1641151 TI - Linkage studies in progressive myoclonus epilepsy: Unverricht-Lundborg and Lafora's diseases. AB - The progressive myoclonus epilepsies (PME) are a heterogeneous group of rare genetic disorders. Unverricht-Lundborg disease and Lafora's disease are two major classic forms of PME. We recently assigned the gene for Unverricht-Lundborg disease (EPM1) to human chromosome 21 band q22.3. We have now refined the localization of EPM1 by linkage analysis between the disease phenotype and nine DNA markers in 13 Finnish families. Loci MX1 and CD18 flank the EPM1 interval, which spans a distance of about 3.5 megabases. In this 20-centimorgan interval, no recombinations were detected between EPM1 and marker loci BCEI, D21S19, D21S42, D21S113, D21S154, and PFKL. Within this interval a maximum multipoint lod score of 11.04 was reached at loci D21S154-PFKL. In two Swedish families with Unverricht-Lundborg disease no recombinations were detected. In three Italian families with Lafora's disease the linkage results suggested that EPM1 is not the locus for Lafora's disease. PMID- 1641152 TI - Effect of BAEP monitoring on hearing preservation during acoustic neuroma resection. AB - We measured the effect of brainstem auditory evoked potential (BAEP) monitoring on hearing preservation in acoustic neuroma resection in 90 consecutive patients with monitoring compared with 90 historical controls matched for tumor size and preoperative hearing status. In small tumors (less than 2 cm), BAEP monitoring was associated with a higher rate of hearing preservation and a greater chance that the hearing preserved was clinically useful. Changes in the BAEP intraoperatively showed a good correlation with postoperative hearing status. PMID- 1641153 TI - Isolated tremor and disruption of the nigrostriatal dopaminergic system: an 18F dopa PET study. AB - We measured striatal 18F-dopa influx constants (Ki) for 20 patients with isolated, predominantly postural, tremor (eight familial, 12 sporadic) and 11 with predominantly rest tremor. Results were compared with 30 controls and 16 Parkinson's disease (PD) patients. The eight familial essential tremor (ET) patients had normal striatal 18F-dopa uptake. Two of the 12 sporadic postural tremor patients had subnormal putamen 18F-dopa Ki, one (who later became akinetic) falling in the PD range. The mean putamen 18F-dopa uptake of the 11 rest tremor patients was reduced to PD levels (51% of normal). Our findings argue against an association between ET and PD, but support the existence of a "benign" tremulous variant of PD. The presence of low-amplitude rest tremor, cogwheel rigidity, reduced arm swing, and short tremor duration was not a useful predictor of nigral dysfunction in patients with postural tremor. In contrast, patients with predominantly rest tremor, particularly with onset in the leg, consistently showed reduced putamen 18F-dopa uptake. PMID- 1641154 TI - Motor and nonmotor behavioral deficits in monkeys made hemiparkinsonian by intracarotid MPTP infusion. AB - We tested five monkeys (three Macaca mulatta, two Macaca nemistrina) made hemiparkinsonian by internal carotid artery infusion of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) for lateralized motor function using a bar press task and a reaction time/movement time task and for hemispatial neglect or hemi inattention using a double simultaneous stimulation (DSS) task, a lateralized reward retrieval task, and a task that assessed response to lateralized moving stimuli. All monkeys had impaired bar press performance and prolonged reaction and movement times with the limb contralateral to the lesion. However, using the limb ipsilateral to the lesion, all animals showed extinction to DSS, that is, they responded to single stimuli presented on the impaired side (contralateral to the MPTP lesion) more often than to stimuli presented on the impaired side that were presented simultaneously with stimuli on the unimpaired side (ipsilateral to the lesion). There was a response bias toward the side ipsilateral to the lesion in the lateralized retrieval task and a deficit in the ability to direct attention toward the side contralateral to the lesion when moving stimuli were employed. These latter results could not be explained by primary motor or sensory impairments. We conclude that unilateral MPTP-induced dopamine depletion in monkeys causes a complex syndrome characterized by overt motor disturbances contralateral to the side of lesion and less overtly apparent sensorimotor integration deficits. PMID- 1641155 TI - In vivo 31P nuclear magnetic resonance spectroscopy of human temporal lobe epilepsy. AB - We performed localized 31P nuclear magnetic resonance (NMR) 1H-image-guided in vivo spectroscopy to study regional high-energy phosphate levels in the brains of normal controls and in patients with intractable unilateral temporal lobe epilepsy. We did not observe differences in intracellular pH between controls and patients. The phosphocreatine/inorganic phosphate ratio was reduced by 50% in the epileptogenic temporal lobe compared with controls (p less than 0.005) and by 35% when compared with the unaffected contralateral temporal lobe (p less than 0.05). We did not observe differences in the ratio of phosphomonoesters to phosphodiesters between controls and patients. These findings suggest that in vivo 31P NMR spectroscopy yields a distinctive interictal metabolic profile in patients with intractable unilateral temporal lobe epilepsy and may permit noninvasive lateralizing evidence of the seizure focus. PMID- 1641156 TI - Propriospinal myoclonus: a neurophysiologic analysis. AB - We are reporting a neurophysiologic analysis of two patients presenting with thoracoabdominal spontaneous muscle jerks. Polymyographic recordings showed myoclonic bursts with onset in the upper rectus abdominis or lower intercostal muscles followed by rostral propagation to the upper intercostal and caudal propagation to the abdominal muscles by slowly conducting pathways. Jerk-locked back-averaging did not show time-locked cortical or premovement potentials. Peroneal somatosensory evoked response, C-reflex, and intercostal nerve conduction were normal. These findings suggest a generator for the myoclonus in the midthoracic region of the spinal cord with up and down propagation by slowly conducting pathways, such as propriospinal fibers. This type of spinal myoclonus may thus be termed "propriospinal myoclonus," as suggested by Brown et al. PMID- 1641157 TI - Prospective serial analysis of interleukin-2 and soluble interleukin-2 receptor in relapsing-remitting multiple sclerosis. AB - We performed a longitudinal analysis of serum interleukin-2 (IL-2) and soluble IL 2 (sIL-2R) concentrations in 60 patients with relapsing-remitting (R-R) multiple sclerosis (MS) as well as in 33 age- and sex-matched normal controls. Overall, we found that serum IL-2 levels remained low (less than 10 U/ml) and did not change appreciably over time; however, marked fluctuations in sIL-2R levels were observed in both the patient and control groups. Using patients as their own controls, we calculated an interrelapse (disease stable) mean sIL-2R concentration as a baseline for comparison with relapse values; sIL-2R levels greater than the 90th percentile of the Student's t distribution of stable values were defined as "peaks." There were a total of 27 sIL-2R peaks, eight (30%) of which correlated with clinical relapses but were potentially predictive of only 18% (8/45) of all the recorded clinical relapses. There was no difference in disease severity (Expanded Disability Status Scale) score between peak-correlated and noncorrelated relapses. Our data suggest that despite reports of elevated levels of IL-2 and sIL-2R in MS, neither may be a useful marker for predicting clinical disease activity in R-R MS. PMID- 1641158 TI - Aortic plaque in patients with brain ischemia: diagnosis by transesophageal echocardiography. AB - We evaluated 183 patients with brain ischemia for an embolic source, using transesophageal echocardiography with extensive imaging of the thoracic aorta. There were mobile, frond-like projections of aortic plaque in seven (4%) patients. The plaque originated on a wide base on the posterior aspect of the ascending aorta at its junction with the transverse arch in six patients, and on the aortic root in one. The acute event was a cerebral infarction in five patients, and a transient ischemic attack in two. This type of aortic plaque could be a previously underdiagnosed source of cerebral embolism that is now easily visualized by transesophageal echocardiography. PMID- 1641159 TI - Interaction of random electromyographic activity with averaged sensory evoked potentials. AB - We averaged sensory nerve action potentials (SNAP) of the median nerve recorded at the wrist, forearm, and elbow with up to 6,000 trials in the presence of quantitated levels of background EMG activity in six normal volunteers. The SNAP could be recorded reproducibly with averaging when the EMG amplitude was up to 50 times the SNAP amplitude. EMG amplitudes of greater than 100 times the SNAP amplitude produced continuous variation in the averaged waveform that did not stabilize, probably because of the quasi-random, large, triphasic potentials that make up the EMG. Monitoring and reduction of background EMG activity can improve reliability of somatosensory evoked potential recording. PMID- 1641160 TI - Vimentin and desmin in maturing skeletal muscle and developmental myopathies. AB - I studied vimentin and desmin immunoreactivities in the skeletal muscle of 30 human fetuses and children ranging from 8 weeks' gestation to 2 years of age, and in 45 infants and children and five adults with developmental neuromuscular diseases. Acridine orange-RNA fluorescence also identified regenerating myofibers in Duchenne muscular dystrophy and dermatomyositis for comparison with congenital myopathies. Vimentin and desmin are both strongly expressed in fetal myotubes and their immunohistochemical demonstration persists until 36 weeks' gestation. These cytoskeletal proteins are uniformly expressed in myofibers of neonates with X linked recessive myotubular myopathy. Desmin but not vimentin is diffusely increased in infantile cases of myotonic dystrophy, in some cases of congenital muscle fiber-type disproportion, and in cerebrohepatorenal disease. In nemaline rod myopathy, desmin is focally increased in perinuclear zones and in regions of aggregated rods. The small myofibers in infantile spinal muscular atrophy show increased vimentin and desmin in the subsarcolemmal region. The demonstration of these intermediate filament proteins provides markers to enhance diagnostic precision in the interpretation of the infant muscle biopsy. Furthermore, persistently high fetal concentrations of vimentin/desmin may play a role in the pathogenesis of some developmental myopathies. PMID- 1641161 TI - The dropped head syndrome. AB - We describe four patients with a neuromuscular syndrome characterized by relatively isolated neck extensor weakness. EMG and muscle biopsies suggest a restrictive noninflammatory myopathy predominantly affecting the cervical paraspinal muscles. PMID- 1641162 TI - Spontaneous intracranial hypotension with pachymeningeal enhancement on MRI. AB - Spontaneous intracranial hypotension (SIH) is a rarely reported syndrome of spontaneously occurring postural cephalalgia associated with low CSF pressure. We report a case of SIH in which MRI of the brain revealed diffuse symmetric pachymeningeal enhancement that resolved without specific therapy. PMID- 1641163 TI - Olfactory function in essential tremor. AB - Olfactory function, assessed by the University of Pennsylvania Smell Identification Test, was normal in essential tremor (ET) patients and significantly reduced in patients with Parkinson's disease (PD). This finding further supports a lack of association between ET and PD. PMID- 1641164 TI - Upper arm radial nerve palsy after muscular effort: report of three cases. AB - Three healthy men were engaged in continuous repetitive arm exercise when a sudden forceful contraction and stretch of the arm muscles led to a delayed upper arm radial nerve palsy. Radial nerve "entrapment" at the lateral head of the triceps muscles is a recognizable occupational nerve injury. PMID- 1641165 TI - Vestibular evoked potentials in human neck muscles before and after unilateral vestibular deafferentation. PMID- 1641166 TI - Lotus neuropathy: report of a case. PMID- 1641167 TI - Recurrent aseptic meningitis complicating intravenous immunoglobulin therapy for chronic inflammatory demyelinating polyradiculoneuropathy. PMID- 1641168 TI - An open-label trial of bromocriptine in nonfluent aphasia. PMID- 1641169 TI - Supplements. PMID- 1641170 TI - Increased dystonia after intrathecal baclofen. PMID- 1641171 TI - L-dopa and narcolepsy. PMID- 1641172 TI - Celiac disease and vitamin E deficiency. PMID- 1641173 TI - Imaging and seizures. PMID- 1641174 TI - Epileptiform spikes. PMID- 1641175 TI - Paget's disease and hemifacial spasm. PMID- 1641176 TI - Selegiline and nigral neurons. PMID- 1641177 TI - Conjugal MS. PMID- 1641178 TI - How many neurologists? PMID- 1641179 TI - Hemispatial neglect. PMID- 1641180 TI - Serum lipid peroxides in patients with Parkinson's disease. AB - To elucidate whether high serum lipid peroxidation rates may increase the risk of developing Parkinson's disease (PD), we assessed serum levels of malondialdehyde (MDA), an intermediate in lipid peroxidation processes, in 37 PD patients, with their spouses as the control group. Serum MDA levels did not differ significantly between these two groups (8.7 +/- 0.51 and 8.8 +/- 0.48 nmol/ml, resp.), and were not influenced by antiparkinsonian therapy in the PD patients. Serum MDA levels were inversely correlated with age and age at onset (P less than 0.01) in the PD group, but they were not correlated with disease duration, Unified Parkinson's Disease Rating Scale scores or Hoehn and Yahr staging. In the control group there was no correlation between serum MDA and age. These results suggest that, although serum levels of lipid peroxides were similar in both the PD and control groups, high serum lipid peroxidation rates might constitute a risk factor for younger onset of PD in predisposed individuals. PMID- 1641181 TI - Presence of diadenosine polyphosphates--Ap4A and Ap5A--in rat brain synaptic terminals. Ca2+ dependent release evoked by 4-aminopyridine and veratridine. AB - The study of the adenine nucleotides in middle brain synaptosomes from rat showed the presence of two diadenosine polyphosphates, Ap4A and Ap5A. HPLC techniques and phosphodiesterase digestion were employed in order to characterize and quantify the dinucleotides. The Ap4A content per mg of protein was 169 +/- 25 pmol and 159 +/- 22 pmol for Ap5A. The study of the exocytotic release of these compounds was carried out with 100 microM 4-aminopyridine or 10 microM veratridine in the presence and in the absence of calcium. 4-Aminopyridine released 14.5 +/- 3.0 pmol/mg protein of Ap4A and 11.6 +/- 2.4 pmol/mg protein of Ap5A in a calcium dependent process. Veratridine in the presence of calcium released 19.9 +/- 3.0 and 16.6 +/- 2.8 pmol/mg of protein of Ap4A and Ap5A respectively. The ratios of exocytosis were close to 7-9% and 10-12% of the total synaptosomal content in the presence of 4-aminopyridine and veratridine, respectively. PMID- 1641182 TI - Immunoreactivities for antisera to three putative neuropeptides of the rat melanin-concentrating hormone precursor are coexpressed in neurons of the rat lateral dorsal hypothalamus. AB - Antisera (AS) raised against rat melanin-concentrating hormone (rMCH) and against two additional peptides sequences derived from the rat MCH precursor (neuropeptide glutamic acid-isoleucineamide (NEI), and neuropeptide glycine glutamic acid (NGE)) exclusively stained the hypothalamic neurons previously described using AS to salmon MCH, human somatocrinin 1-37 (GRF37) and alpha-MSH. Liquid phase and dot-blot controls for specificity indicated that rMCH-, NEI- and NGE-AS bound epitopes recognized by sMCH-, alpha-MSH- and GRF-37-AS, respectively. The distinct intracellular patterns of immunoreactivity obtained in control animals with rMCH-, NGE- and NEI-AS, as well as the changes observed after intracerebroventricular injection of colchicine matched previous findings using sMCH-, GRF37- and alpha-MSH-AS. PMID- 1641183 TI - The effect of binocular lid suture on auditory responses in the guinea-pig superior colliculus. AB - Guinea-pigs were deprived of visual experience from soon after birth until the terminal auditory mapping experiment (performed between 57 and 96 days after birth). The visual deprivation was effectuated by binocular eyelid suture. Multi unit responses were obtained from the superior colliculus (SC) in response ot free field presentation of bursts of broad band noise. In lid sutured animals a topographically ordered auditory map of azimuthal space was demonstrated in the SC. The auditory responses were, however, not as precise or tuned when compared with normal animals. Nevertheless, lid sutured animals were not as severely affected as dark reared animals in which no auditory map is evident in the SC. This study thus highlights the difference between binocular lid suture and dark rearing as methods of visual deprivation. PMID- 1641184 TI - Estimation of neural architecture in human brain by means of the dipole tracing method. AB - The electric source locations of interictal spikes recorded with depth electrodes were estimated by the dipole tracing (DT) method. Three-dimensional coordinates of the active surfaces of the depth electrodes and head geometry of the patient were measured from frontal and sagittal X-ray images and by a special device, respectively. The estimated dipole locations were superimposed on MR images of the patients. The dipole locations estimated in the hippocampal or parahippocampal regions successively moved in a small limited region during the interictal spike's peak. It was suggested that an interictal spike is composed of summated equivalent dipoles generated by hypersynchronization of a cluster of neurons, and that the timing of such hyperexcitation is more or less delayed because of electrical propagation along neuronal clusters which might be separated by sclerotic tissues. PMID- 1641185 TI - Human circadian rhythm in serum melatonin in short winter days and in simulated artificial long days. AB - Serum melatonin rhythm was studied in 6 human subjects experiencing short winter days resembling light/dark (LD) 8:16 h and in 6 subjects exposed at the same time to a long, LD 16:8 h skeleton photoperiod, with 3 h of bright light in the evening and again in the morning; 4 out of the 6 subjects entrained to the simulated summer photoperiod within 3 days. In the synchronized subjects, the nocturnal melatonin signal was 3 h shorter than in those experiencing just winter days. The data indicate that humans are able to respond to environmental day length by forming a proper endogenous photoperiodic signal. PMID- 1641186 TI - Immunocytochemical localization of VIP-immunoreactive neurons in the hypothalamus of immature gilts. AB - Immunocytochemical study using avidin-biotin complex method and peroxidase antiperoxidase technique was carried out to determine the distribution and morphology of vasoactive intestinal polypeptide-immunoreactive (VIP-IR) neuronal structures in the hypothalamus of the immature female pig. VIP-IR neurons were found in the arcuate, paraventricular and supraoptic nuclei, as well as in the pituitary stalk. The median eminence disclosed an abundance of VIP-IR processes both in the internal and external layer. These results let us conclude that there exist convenient morphological conditions for the release of VIP into portal blood in the area of the porcine median eminence-pituitary stalk complex. PMID- 1641187 TI - In situ transformation of striatal glia into cerebellar-like glia after brain transplantation. AB - Transplants of striatum from rabbit embryo were implanted into the colliculus posterior of newborn mice. After 4 weeks, astroglial cells derived from the transplant had migrated into the cerebellum of the host. Whenever they had settled in the cerebellum they presented forms similar to local glia. Some migrated glial cells were found to transform into forms of glia, such as radial like glia, which are not present in the striatum. This observation confirms that glial precursor cells are highly plastic. It is an in vivo demonstration that local conditions alone define the morphology of glial cells. After grafting in an heterotopic location they take on forms that they were not destined to express in the region of origin. PMID- 1641188 TI - Early modification of neuropeptide Y but not of neurotensin in the suprachiasmatic nucleus of the obese Zucker rat. AB - Hyperphagia in the obese Zucker rat is characterized by the early modification of the dark/light (D/L) rhythm of food intake. This rhythm is mainly driven by the suprachiasmatic nucleus (SCN) and, more controversially, by the ventromedian nucleus (VMN). In the SCN of adult obese Zucker rat, the concentrations of neuropeptide Y (NPY), a potent stimulator of food intake, are increased whereas those of neurotensin (NT), an anorexigenic peptide, are decreased. However, nothing is actually known about the synchronicity of the dysregulation of the D/L rhythm and variations of these peptides. That is why we measured NPY and NT in the microdissected SCN and VMN of lean (n = 16) and obese (n = 15) Zucker rats before the occurrence of hyperphagia (day 16 of age) and a few days after weaning (day 30 of age) when the modifications are apparent. For NPY, there was a very significant effect of age (P less than 0.001) for both nuclei and a significant effect of genotype (P less than 0.02) for the SCN only. NPY concentrations increased between 16 and 30 days in both nuclei (+74% (SCN) and +70% (VMN) in the obese rat; +57% (SCN) and +67% (VMN) in the lean rat; P less than 0.001). NPY in the SCN was not different at 16 days of age between lean and obese rats but significantly increased at 30 days in the obese rat (22.6 +/- 1.2 vs. 18.6 +/- 1.5 ng/mg protein; P less than 0.05). NT was not detected in the SCN of either group at 16 days or at 30 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641189 TI - Localization of interleukin 6 mRNA and interleukin 6 receptor mRNA in rat brain. AB - The cytokine interleukin 6 (IL6) has several effects on the central nervous system in addition to the well established regulation of the acute phase inflammatory response. Therefore, the distribution of IL6- and IL6 receptor mRNA in the rat brain has been investigated by in situ hybridization using [35S] labeled oligonucleotides. The messages of both genes were found in the CA1-CA4 regions as well as in the dentate gyrus of the hippocampus, in the habenulae, the dorsomedial and the ventromedial hypothalamus, in the internal capsule, the optic tract and in the piriform cortex. These data indicate both neuronal and glial localization of IL6 and IL6 receptor and their involvement in an autocrine or paracrine action of the cytokine in centrally regulated functions including neuroendocrine control. PMID- 1641190 TI - The neuropeptide schistosomin and haemolymph from parasitized snails induce similar changes in excitability in neuroendocrine cells controlling reproduction and growth in a freshwater snail. AB - Infection of the snail Lymnaea stagnalis with the schistosome parasite Trichobilharzia ocellata results in inhibition of reproduction and in giant growth. Parasite-related effects on the neuroendocrine centres that control these processes were studied electrophysiologically. Haemolymph from infected snails reduced the excitability of the caudodorsal cells, which control egg laying. In contrast, the excitability of the growth-controlling Light Green Cells was increased under these conditions. The endogenous anti-gonadotropic neuropeptide schistosomin, the presence of which is strongly enhanced in parasitized snails, induced similar effects. Schistosomin apparently plays an important role in the balance between reproduction and growth in Lymnaea. This balance is severely disturbed during parasitic infection, probably as a result of the release of the peptide. PMID- 1641191 TI - Effect of viscosity on neurite outgrowth and fractal dimension. AB - The growth mechanism by which neurons achieve their characteristic ramified morphology has long been of interest, but determining whether physical parameters, such as viscosity, are important has been difficult due to a lack of useful hypotheses and standard reproducible techniques. We have recently shown that neurons exhibit fractal behavior and that their fractal dimension (df) is consistent with a physical process called diffusion-limited aggregation (DLA). We suggested that this DLA behavior might stem from viscosity differences, chemical gradients or electrical fields (Caserta et al., Phys. Rev. Lett., 64 (1990) 95 98). DLA is a model for a large family of growth processes. In order for a process to fit the DLA model, the growth rate must be proportional to the gradient of a field at a point on the growing structure (Feder, Plenum, New York, 1988, Ch. 4). Chemical, electrical, or fluid pressure fields can fit the model depending on the particular physical system under study. Here, we studied growth of retinal neurons from chick embryos in culture media of various fluid viscosities. Thus, we test whether DLA in this system was based on a fluid pressure field. As viscosity was increased from 1 to 4.3 cps, the number of neurite branches decreased 98%. However, there was no effect on df. Over this range of viscosities, total cellular protein synthesis decreased only 17%. The results indicate that, while differences in viscosity between the interior and exterior of the cell affect neurite outgrowth, they do not affect the fractal behavior of neurons. Thus, viscosity differences are not the basis for the DLA pattern of neuronal arborization. PMID- 1641193 TI - Periodic amplitude modulation of EEG. AB - Time variation of the EEG spectral parameters was analyzed during a 10 min resting period in 40 healthy subjects. Spectral band powers over the theta and alpha bands were calculated for each non-overlapping 2.5 s long EEG segment. The time variation of the band powers was further analyzed by computing the power spectra. The results showed that both theta and alpha band powers oscillate at an average frequency 0.024 Hz and 0.057 Hz. This indicates, that the background EEG activity is modulated by periodical slow components. We hypothesize that this modulation reflects spontaneous periodic changes of cortical excitability with control at the brainstem level. PMID- 1641192 TI - Activation of basal forebrain cholinergic neurons differentially regulates brain derived neurotrophic factor mRNA expression in different projection areas. AB - Afferent cholinergic pathways from the basal forebrain were activated by injections of the glutamate analog quisqualate either into the nucleus basalis or into the medial septal nucleus. Nucleus basalis injections had no effect on the expression of brain-derived neurotrophic factor (BDNF) mRNA in its neocortical projection areas as measured by in situ hybridization. In contrast, 7 h after an injection into the septum the level of BDNF mRNA increased 3- to 5-fold in the dentate gyrus, throughout CA1 to CA3 in the hippocampus and in the piriform cortex. PMID- 1641194 TI - Axotomy induces fusimotor-free muscle spindles in neonatal rats. AB - Crushing the nerve to the medial gastrocnemius (MG) muscle at birth and administering nerve growth factor to rats afterwards results in a reinnervated muscle with supernumerary muscle spindles, some of which must have formed de novo. Structure and innervation of spindles in the reinnervated MG muscles were studied in serial 1 micron transverse sections. Two types of spindle-like encapsulations were observed. The prevalent type consisted of one to three small diameter intrafusal fibers with features of nuclear chain fibers or infrequently a nuclear bag fiber. The second type of encapsulation consisted of the small diameter fibers located in a compartment which abutted a compartment containing a large diameter extrafusal fiber. All intrafusal fibers in spindles of the experimental muscles were innervated by afferents, but most of them (85%) were devoid of efferent innervation. Thus, immature fusimotor neurons may be more susceptible than spindle afferents to cell death after axotomy at birth. PMID- 1641195 TI - Quantitative autoradiography of 5-CT-sensitive (5-HT1D) and 5-CT-insensitive (5 HT1E) serotonin receptors in human brain. AB - Quantitative receptor autoradiography was used to determine the distribution patterns of 5-CT-sensitive and 5-CT-insensitive binding of [3H]5-HT to high affinity sites in human cortex, putamen, and globus pallidus. The binding of 3H-5 HT was limited to 5-HT1D sites (5-CT-sensitive) by co-incubating pindolol and mesulergine with [3H]5-HT, and by using 10 microM 5-HT to determine non-specific binding. The difference in the levels of binding between tissues exposed to the 5 CT-containing incubation media and tissue exposed to [3H]5-HT in the presence of 100 nM 5-CT was defined as 5-CT-insensitive binding (5-HT1E). The 5-HT1D receptor density in the frontal cortex was 189 fmol/mg, 226 fmol/mg was present in the globus pallidus, while the density in the putamen was only 28 fmol/mg. The 5-HT1E receptor density was 146 fmol/mg in frontal cortex, 224 fmol/mg in putamen and 140 fmol/mg in globus pallidus. The differential distribution patterns of the high-affinity, 5-CT-sensitive and 5-CT-insensitive [3H]5-HT binding sites indicate that these sites are expressed independently in human brain tissues. These data are supportive of and consistent with previous pharmacological data that led to the division of 5-HT1D receptors into 5-HT1D and 5-HT1E receptors and do not support the division of 5-HT1D receptors into 5-CT-sensitive and 5-CT insensitive states. PMID- 1641196 TI - Differential effects of platelet-derived growth factors on fetal hippocampal and cortical grafts: evidence from intraocular transplantation in rats. AB - Effects of platelet-derived growth factor-AA (PDGF-AA) and platelet-derived growth factor-BB (PDGF-BB) on developing parietal cortex (E16) and hippocampal (E18-E19) grafts were studied using the in vivo method of intraocular transplantation. Survival and growth of grafts in the anterior eye chamber of adult host rats under the influence of regular treatments with 0.5 ng (in a 100 ng/ml concentration) PDGF-AA or PDGF-BB was followed and compared to those receiving vehicle solution alone (0.5 mg HSA/ml Hanks). Both PDGF-AA and PDGF-BB increased the volume of transplanted cortical grafts. PDGF-BB also exerted trophic effects on grafted hippocampal tissue whereas PDGF-AA seemed to inhibit hippocampal growth. Histological and immunohistochemical studies revealed an increase in the density of astroglial elements in PDGF-AA- and PDGF-BB-treated cortical grafts whereas the PDGF-AA- and PDGF-BB-treated hippocampal grafts maintained a cytoarchitecture closely resembling that of control grafts. These findings support in vitro experiments showing that developing glial cells are stimulated by PDGFs and we further propose regional differences of action of PDGFs in the developing central nervous system. PMID- 1641197 TI - Nutrition and health of elderly people in Europe: the EURONUT-SENECA Study. AB - In 1988 EURONUT, the umbrella European Community (EC) Concerted Action on Nutrition and Health, initiated a major European multicenter study, named SENECA,* to study cross-cultural differences in nutritional issues and life-style factors affecting health and performance of elderly people in Europe. According to a strictly standardized methodology, 2,586 elderly subjects--born between 1913 and 1918--have been studied in 19 towns across Europe, using a mixed longitudinal design. Data regarding nutrient and food intakes, diet habits, diet awareness, nutritional status, health, and life-style factors were collected and are partially presented in this paper. There was considerable variability from site to site--even within countries--in dietary intake, in both quantity and composition; blood biochemistries; life-style factors; health; and performance. Implications of the observed wide variability will be studied longitudinally. PMID- 1641198 TI - How does fish oil lower plasma triglycerides? AB - Studies using dietary fish oil, safflower oil, and palm oil suggest that the decrease in plasma triacylglycerol due to dietary fish oils is somehow related to a decrease in the capacity of the liver to hydrolyze the phosphatidate, which then affects microsomal synthesis of triacylglycerol from diacylglycerol. PMID- 1641199 TI - Cellular retinol-binding protein functions in the regulation of retinoid metabolism. AB - A microsomal retinyl ester hydrolase from rat tissues is activated by apo cellular retinol-binding protein, which thus regulates the availability of retinol either for binding to serum retinol-binding protein or for metabolic oxidation. Microsomal retinal synthesis was found to occur in rat tissues with holo-cellular retinol-binding protein as substrate. Retinal could be further oxidized to retinoic acid by a cytosolic fraction. PMID- 1641200 TI - Growth-hormone therapy for short children without growth-hormone deficiency. AB - The daily subcutaneous injection of 0.3 U/kg of recombinant growth hormone (GH) for the two years prior to puberty in ten constitutionally growth-retarded children with normal pituitary function resulted in an average height gain of 10 cm per year. No manifestations of GH excess were seen, and a transient alteration in glucose metabolism was resolved after treatment. PMID- 1641201 TI - Determinants of energy utilization in patients with cystic fibrosis. AB - Resting energy expenditure (REE) is increased in patients with cystic fibrosis, a consequence of the work of breathing and not related to the cystic fibrosis (CF) gene. CF patients compensate, however, with reduced energy expenditure for activity and thermogenesis, thereby maintaining total energy expenditure (TEE) equivalent to that of healthy peers. PMID- 1641202 TI - Treatment of patients with alcoholic liver disease with casein-based enteral nutrition. PMID- 1641203 TI - The data support a role for antioxidants in reducing cancer risk. PMID- 1641204 TI - The viable serotonin hypothesis. PMID- 1641205 TI - Common interests and shared objectives. PMID- 1641206 TI - Providing access to obstetric care in New York State. PMID- 1641207 TI - Professional liability reform and access to Medicaid obstetric care in New York State. AB - Professional liability costs and fear of lawsuits have made participation in Medicaid difficult for office-based physicians who provide prenatal care, both obstetricians and family physicians. We assessed the possible impact of changes in three liability policy reforms on expanding access of Medicaid-eligible pregnant women to these private physicians. We surveyed members of the New York State District of the American College of Obstetricians and Gynecologists and the New York Academy of Family Physicians to explore whether they would start, expand, or resume obstetric service to Medicaid patients in response to a ceiling on litigation awards, no-fault insurance and a subsidy for liability expenses. We then compared the reported increases in participation on the basis of liability reforms to those in response to changes in Medicaid policies. We found in general that the three liability reforms would have similar impacts on Medicaid participation, although a subsidy was indicated by fewer physicians than the ceiling or no-fault approaches. The support for the liability reforms was as effective as proposals of greater reimbursement rates. The proportion of obstetricians or family physicians increasing their participation depended more on whether they would be starting Medicaid participation, expanding existing Medicaid participation or resuming former Medicaid participation than on the particular liability policy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641208 TI - Total serum cholesterol levels in Asians living in New York City: results of a self-referred cholesterol screening. AB - Asians historically have low total cholesterol levels and low incidence of coronary heart disease. In performing a coronary heart disease and total cholesterol screening in New York City's Chinatown, we obtained data supportive of previous studies, which focused on Japanese populations and described the influence of environment on total cholesterol. In the present study, Chinese living in Chinatown have higher levels of total cholesterol than would be expected from studies of Chinese living in Shanghai. For every age group examined, Asian-born Chinese living in Chinatown had higher total cholesterol levels than both urban and rural Chinese in Shanghai. In subjects less than or equal to 30 years of age, urban males in Shanghai had cholesterol levels of 160 +/- 34 mg/dL, compared with 206 +/- 38 mg/dL for Asian-born males in Chinatown. For females in the same age category, cholesterol levels were 162 +/- 35 mg/dL vs 224 +/- 45 mg/dL, respectively. Applying National Cholesterol Education Panel (NCEP) guidelines, the distribution of desirable, borderline-high, and high blood cholesterol levels for the Chinese in Chinatown (41%, 35%, and 23%, respectively) were similar to a group of Caucasians screened (42%, 32%, and 26%) and the group recently used to determine the prevalence of high blood cholesterol in American adults (43%, 30%, and 27%). Studies are needed to stratify the risk of coronary heart disease in other groups that traditionally have a low incidence of coronary heart disease, but which now have adopted Western lifestyles. PMID- 1641209 TI - The antihypertensive effects of exercise training. PMID- 1641210 TI - Skin changes associated with hematologic and oncologic diseases in children. PMID- 1641211 TI - The story of Lassa fever. Part II: Learning more about the disease. PMID- 1641212 TI - Low-dose vincristine-associated bilateral vocal cord paralysis. PMID- 1641213 TI - Tuberculous peritonitis as an initial manifestation of HIV infection. PMID- 1641214 TI - An unusual manifestation of testicular lymphoma. PMID- 1641215 TI - Intralymphatic immunotherapy of glioblastoma. PMID- 1641216 TI - Nocardia brasiliensis soft tissue infection in an immunocompromised host. PMID- 1641217 TI - Low technology and the prevention of nosocomial AIDS. PMID- 1641219 TI - Illegal drug use. PMID- 1641218 TI - Illegal drug use. PMID- 1641220 TI - Illegal drug use. PMID- 1641221 TI - Foveal photopigments. AB - The relative rates of absorption of quanta per unit of energy for the various wavelengths can be assessed for the human red, green, and blue photoreceptors by assuming that the responses generated by a photoreceptor are proportional to the rate of absorption of quanta. We start by selecting three points on the color mixture diagram to represent the fundamental colors. The mixture diagram is then transformed to a constant luminance diagram in which the fundamental colors serve as primaries. The V(lambda) values are then multiplied by the chromaticity coordinates (r, g, and b) to determine the response curves of red, green, and blue cones. The values of V(lambda)r, V(lambda)g, and V(lambda)b are divided by the transmittance of the ocular media and the wavelength to give the relative absorptions. No allowance has been made for self-screening or population densities. I have used the Judd (V(lambda) curve and the Wright-Guild mixture data. I have found three fundamental colors which yield predictions for the absorption curves of the photopigments of the foveal cones which conform well to the absorbance curves measured directly. PMID- 1641222 TI - Variation of the hyperacuity gap function with age. AB - Responses to hyperacuity stimuli are processed in quite a different manner by the central nervous system than many other stimuli such as resolution targets or increment threshold stimuli. With increased attention being paid to visual response in aging individuals, it is important to study how these response paradigms are affected by age. In this analysis, otherwise normal observers 20 to 85 years of age were studied. The hyperacuity gap test was used. As defined, this is a vernier test using a two-point test array. This particular format was chosen because the resultant data are less distorted by image blur, scatter, and astigmatism than other designs we have studied. The gap or feature separation between the two small targets (which were aligned vertically) was increased logarithmically using octave steps and the hyperacuity threshold (setting variance) was measured for each step. No systematic variation of vernier hyperacuity threshold was found with increasing age within the range of ages or gaps tested. This is important because it can serve as a valuable control and reference for other clinical studies of aging. PMID- 1641223 TI - The Cardiff Test: a new visual acuity test for toddlers and children with intellectual impairment. A preliminary report. AB - We have developed a new test for acuity measurements specifically designed for the hard to test group of toddlers and children with intellectual impairment. The test uses vanishing optotypes and the preferential looking technique. Comparison studies with established acuity tests, Snellen, Cambridge and Teller cards show that the test provides a realistic acuity measure. It is highly successful for toddlers and children with intellectual impairment and quicker to administer for the toddler age group. PMID- 1641224 TI - Assessment of visual function in autistic children. AB - Children with autism demonstrate "atypical" gaze or social "looking" and frequently manifest such sterotypies as eye pressing, hand flicking, and light gazing. This study's purpose was to evaluate autistic children for visual dysfunction that may be related to the manifested visual signs and symptoms. Thirty-four autistic children, ages 2 to 11 years (median age = 7 years, 6 months) were evaluated for ocular alignment, refractive error, visual acuity, oculomotility skills, and stereopsis. None of the children manifested ocular disease, known seizure disorders, or dysmorphic features. Their developmental levels ranged from average intelligence to severely retarded. Binocular visual acuity was measured with the acuity card procedure. Monocular visual acuity was not obtained. Refractive errors ranged from -4.25 to +3.25 D; the median was plano with the near retinoscopy technique. Of the 34 children, 21% were strabismic at far and 18% were strabismic at near. Lang stereo testing was attempted on all children and completed on 17. Of the 17, all but 3 exhibited 550 sec arc. Only 14.7% of the children exhibited voluntary pursuit movements, and all the children demonstrated saccadic fixations. Thirty-one children had atypical optokinetic nystagmus (OKN) responses such as delayed onset, short duration, gaze avoidance, or stereotypic behavior. Repeated testing revealed consistent visual responses on OKN and visual acuity. Given these findings, research with this population should be pursued further. PMID- 1641225 TI - A new technique to measure contrast sensitivity in human infants. AB - We used a new time-efficient procedure to obtain binocular contrast sensitivity functions (CSFs) from 80 infants aged 1-, 3-, 6-, and 12-months-old. The test consisted of 5 sets of large (50 by 28 cm) cards constructed by mounting a 7.2 degrees circular sine wave grating with 1 of 5 spatial frequencies (0.3, 0.6, 1.2, 2.4, and 3.6 cpd at 60 cm) onto light gray matteboard. Each card also contained a second 7.2 degrees unpatterned patch of equal space-average luminance. Depending upon the set, the contrast within the gratings ranged from approximately 25 to 0.5%. To judge the subject's detection of each grating we used a rapid version of preferential looking (PL) similar to that developed for the Teller Acuity Cards. Results showed that compared to previous techniques, the card procedure allows one to estimate an infant's CSF much more simply, rapidly, and inexpensively. PMID- 1641226 TI - Refinement of an optical device that stabilizes vision in patients with nystagmus. AB - An optical device that produces partial stabilization of retinal images has been described. It consists of a high-plus spectacle lens used in combination with a large, high-minus, polymethyl methacrylate (PMMA) contact lens. This device is designed to provide more clear and stable vision in patients with acquired nystagmus due to neurological disease. We report success in using a smaller, rigid, gas permeable (RGP) contact lens that achieves the required degree of stabilization, but is more comfortable for patients than the PMMA contact lens originally described. We have confirmed that the degree of retinal image stabilization is similar to that achieved with the PMMA lens. We present a case report to illustrate its use. PMID- 1641227 TI - Effect of the use of artificial tears on the size of squamous cells of the rabbit corneal epithelium evaluated by scanning electron microscopy. AB - Female pigmented rabbits (2 to 2.3 kg) received 2 drops of a chlorobutanol 0.5% preserved, polyvinyl alcohol-based artificial tear at 21.00 h and 09.00 h for 1, 2, 3, 6, or 12 days. The animals were euthanized at 15.00 h and the corneas fixed with 2.0% glutaraldehyde in 80 mM cacodylate buffer. Scanning electron micrographs were taken close to the corneal center at 500 x magnification and normal to the epithelial surface. The surface areas of the squamous cells were measured with a digitizer pad. As a result of the treatment, up to 9% of the cells were observed to be in the process of exfoliation with the effect being greatest after 3 days. Control (nontreated) corneas showed only 0.44% exfoliating cells. Over this time period there was a progressive shift of cell sizes to larger values followed by recovery back to control values by 12 days. The results confirm the lack of gross cytotoxic effect of chlorobutanol-preserved artificial tears and indicate that the corneal epithelium can adapt to the use of a polymer containing artificial tear. PMID- 1641228 TI - Flicker visual evoked potential differentiation of glaucoma. AB - We have been recording visual evoked potentials (VEP's) produced by a series of increasing rate flicker stimuli to find early neuronal loss in chronic open-angle glaucoma patients and suspects. This technique has demonstrated selective early signal losses in high flicker frequency responses (25 and 31 Hz). This signal loss can precede the characteristic arcuate losses found with automated perimetry. In this retrospective study, 428 visual fields were graded and grouped with their associated cup/disk ratios, peak recorded intraocular pressures (IOP's), and flicker VEP measures in a population of patients either diagnosed with glaucoma or at risk for glaucoma (glaucoma suspects). The correlation of selective high frequency (31 Hz) flicker VEP amplitude loss with visual field damage was confirmed. More severe VEP losses correlate well with optic cup size and visual field grade, but not with peak recorded IOP. Phase angle data did not differentiate between populations separated by visual field losses and VEP amplitude measurements. PMID- 1641229 TI - Color defective drivers and safety. AB - At least seven million drivers in North American cannot reliably identify red and green lights. The common assumption by traffic authorities that no serious problems exist is contradicted by the data on color vision, the testimonies of color defective drivers, studies under controlled conditions, and by reliable accident statistics. Color defective drivers can be provided with the same measure of traffic light safety as for normals. Brake lights on vehicles can be made equally effective for color defectives. Suggestions are provided to help those with color defective vision to compensate for their problems. PMID- 1641230 TI - Prevalence of myopia and myopic progression in a population of clinical microscopists. AB - The frequency of refractive errors in a population of clinical microscopists is presented. The prevalence of myopia in this population (N = 251) was found to be 71%, with 49% of the population reporting onset or progression of myopia after entry into clinical microscopy (after 21 years of age). Of subjects undergoing renewed progression of an existing myopia since starting clinical microscopy, 56% reported no refractive change for the 5 years before entering their profession. Accuracy of reporting refractive changes was found to be high. No differences were found in task-related functions between those subjects reporting myopic change in adulthood from those who did not report myopic change. PMID- 1641231 TI - Comparative visual performance of three presbyopic contact lens corrections. AB - We compared the visual performance of a soft diffractive (DIFF) bifocal contact lens, a near center (CN) concentric bifocal design, and monovision (MV), using a comprehensive vision testing protocol. Fifteen presbyopic subjects who were successfully wearing DIFF bifocal contact lenses participated in the study. Of the three systems tested, MV provided best visual acuity at distance and near; less than one line of acuity was lost relative to best spectacle acuity under all lighting and contrast conditions, and there was less disturbance of a point source of light. Both bifocal corrections gave similar visual acuity performance, with more lines of acuity lost relative to spectacles at near compared to distance. However, the concentric bifocal induced more ghosting at near than the other two systems. Stereopsis was compromised at distance with MV correction, but all systems performed worse than spectacles at near. An understanding of the strengths and weaknesses of presbyopic contact lens options allows the clinician to improve management of the presbyope who wishes to wear contact lenses. PMID- 1641232 TI - Review of Horner's syndrome and a case report. AB - Sympathetic denervation of the eye [Horner's Syndrome (HS)] usually presents as ptosis, miosis, and facial anhydrosis. HS presents a challenge to the clinician because the causative lesion may involve a first, second, or third-order neuron. This paper reviews the literature regarding HS, the anatomy of the sympathetic pathway to the eye, the diagnosis, and the localization of the lesion. Our patient developed reversible HS after a migrainous episode which presumably caused "bruising" of the sympathetic plexus within the carotid canal. PMID- 1641233 TI - A case of monocular triplopia of lenticular origin. AB - A 70-year-old male experienced unilateral monocular triplopia of lenticular origin. The images formed a nearly equilateral triangle and were equally clear. It was noted that the images were formed by sections of the crystalline lens whose borders were parallel to the orientation of the anterior Y-sutures. PMID- 1641235 TI - Tools of the trade: enhancing teaching with computers. PMID- 1641234 TI - Is intraocular pressure a risk factor in contact lens wear? AB - Adherence of a rigid gas permeable (RGP) contact lens to the cornea is an unsolved clinical problem in extended wear. This communication proposes that intraocular pressure (IOP) is a cofactor of this phenomenon. Intradiem fluctuations in the IOP can additionally stress the corneal epithelium and affect its biomechanical properties. The corneal surface is then susceptible to lens imprinting and eventual lens immobilization. The prevalence of lens adherence in the morning correlates with the early morning peak in IOP that is known to occur in many normotensive patients. The possibility arises that lens immobilization during sleep is causally related to the peak in IOP. PMID- 1641236 TI - Binocular vision section. AB - The participants at the 1991 Meetings of the Section on Binocular Vision and Perception presented a substantial amount of valuable theoretical and clinical information. There was considerable and valuable interaction between the audience and panel, especially after the symposium concerned with new techniques and how to use them. The exchange of specialized knowledge through discussions at symposiums such as these represents one of the best features of Academy meetings. These symposiums reemphasize and remind us of the expertise of our Academy members in management of binocular vision anomalies. PMID- 1641237 TI - Plasmodium falciparum: isolation of intact and erythrocyte-free trophozoites from sorbitol lysates. AB - An in vitro culture of Plasmodium falciparum (isolate FCUP-1/RSA) was arrested in the trophozoite stage with alpha-difluoromethylornithine (DFMO), followed by sorbitol treatment to liberate intracellular parasites from infected erythrocytes. Most of the unlysed erythrocytes and ghost membranes were removed by filtration, after agglutination with anti-erythrocyte monoclonal antibodies or wheat-germ agglutinin. A highly purified parasite preparation was obtained after chromatography on an immuno-affinity column consisting of polystyrene particles to which anti-erythrocyte monoclonal antibodies had been adsorbed. Isolated parasites were free of surrounding erythrocyte membranes and structurally intact as assessed by transmission electron microscopy, SDS-PAGE and ELISA. PMID- 1641238 TI - Gametocyte sex ratios as indirect measures of outcrossing rates in malaria. AB - The frequency of recombination between unlike genotypes is central to understanding the generation of genetic diversity in natural populations of malaria. Here we suggest a way of investigating the problem which could complement conventional biochemical approaches to the population genetics of malaria. Sex allocation theory is one of the most successful areas of evolutionary biology. A well-supported prediction is that progressively less female-biased sex ratios are favoured with more outcrossing; equal numbers of males and females being evolutionarily stable in randomly mating outbred populations. We present a simple game theory model to support the idea that outcrossing rates in malaria will be correlated with the sex ratio of gametocytes in the peripheral blood of vertebrate hosts. Blood films from epidemiological surveys and culture-adapted isolates from Madang Province, Papua New Guinea, were used to estimate average gametocyte sex ratio of Plasmodium falciparum in the area. The geometric mean proportion of males in the population was 0.18 (95% confidence limits: 0.15-0.22). From our model, we estimate that, on average, 36% of zygotes are the result of outcrossing. This estimate assumes that most microgametes released following exflagellation are capable of fertilization. If, on average, fewer than about 70% of microgametes are capable of fertilization (as is the case in at least one other species of Plasmodium), the observed sex ratio would be consistent with between zero and 36% of zygotes being the result of outcrossing. These estimates suggest that there is usually a numerically dominant genotype in the gametocyte population in a blood meal, and that a considerable amount of selfing is occurring in P. falciparum populations in the Madang region, even though it is an area of intense year-round transmission. PMID- 1641239 TI - A gene associated with cell division and drug resistance in Giardia duodenalis. AB - A 3000 bp cDNA insert (G6/1) from Giardia duodenalis, cloned into Escherichia coli is located on chromosome 3 of Giardia stocks which have 3 chromosomes detectable by field-inversion gel electrophoresis in the range 650-800 kb and on chromosome 3 and/or 4 of stocks with 4 chromosomes in this size range. The loss of this sequence from chromosome 4 but not chromosome 3 was associated with the induction of drug resistance in a previously sensitive laboratory stock. G6/1 appears to represent a single copy gene in Giardia as determined by hybridization of the probe to cleaved genomic DNA. Furthermore, the sequences flanking at least 12 kb of G6/1 are the same when G6/1 appears on both chromosomes 3 and 4. The cDNA encodes a protein associated with the nuclei of trophozoites during some stages of growth of the parasite. In a non-dividing culture, the antigen is associated with the nuclei of about 30% of trophozoites and fewer in a dividing culture. Three Giardia stocks with obvious chromosome rearrangements, which grow poorly and fail to divide normally, apparently lack the DNA sequence G6/1. PMID- 1641240 TI - Repeated infection of cats with Brugia pahangi: parasitological observations. AB - Cats were repeatedly inoculated with infective larvae of Brugia pahangi. On parasitological grounds they could be divided into 5 groups. Group I--most cats (some 70%) became microfilaraemic (mf+) and retained high levels of microfilariae (mf) in their blood for over 2 years. In some Group I cats mf counts stabilized at high levels whilst in others mf counts continued to increase. Large numbers of fecund adult worms were recovered from their lymphatics. Adult counts were not made on the cats in the current experiments but over 100 adults have been recovered from 'super-susceptible' cats. Large amounts of B. pahangi adult antigen were consistently present in the serum of all Group I cats. About 30% of cats became amicrofilaraemic (mf-). In these cats the peak mf levels were seldom above 10,000 mf/ml. Group II--these cats had less than 10,000 mf/ml and low antigen levels. After more than 1 year of being repeatedly infected B. pahangi adult antigen slowly declined and eventually could no longer be detected in their serum and the number of mf declined very slowly after the fall in antigen levels. This shows that in Group II cats the adult worms die and as the cats are resistant to the development of the continuing weekly inoculation of L3 no new adults can develop. Group III--these cats became mf--during the first year of infection but remained B. pahangi antigen-positive for many weeks after this and, at autopsy, had living adults in their lymphatics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641241 TI - Adaptation of a radioactive L. donovani complex DNA probe to a chemiluminescent detection system gives enhanced sensitivity for diagnostic and epidemiological applications. AB - The cDNA probe, Lmet2, was labelled with digoxigenin and used in a chemiluminescent system to detect fewer than 100 membrane-immobilized Leishmania parasites. The probe was found to hybridize primarily with members of the L. donovani complex but a slight cross-reaction was also observed with greater than 5 x 10(4) L. major. This cross-reaction was reduced by hybridizations in 50% formamide at 37 degrees C. Formamide also significantly reduced non-specific binding of the digoxigenin-labelled probe to the membrane support which, in hybridizations without formamide, masked the specific hybridization signal. This background was not observed with the corresponding radio-isotope labelled probe. With hybridizations in formamide the sensitivity achieved by the chemiluminescent system after exposure to film for 3 h was greater than that achieved by the isotopic system even after autoradiography for 24 h. PMID- 1641242 TI - Naturally occurring immunoglobulin M antibodies: enhancement of phagocytic and microbicidal activities of human neutrophils against Toxoplasma gondii. AB - Naturally occurring immunoglobulin M antibodies to Toxoplasma gondii in human sera were examined for their ability to enhance toxoplasmacidal activities of human neutrophils to show a role of natural antibodies in immunity to the early stage of Toxoplasma infection in humans. Neutrophils were mixed with tachyzoites at a ratio of 1:5 in the presence or absence of antibodies and were cultured for 1-18 h for microscopical examination. The count of tachyzoites phagocytosed in 200 neutrophils within 1 h was significantly higher in the presence of sera with natural IgM antibody levels of greater than 0.8 than those of less than 0.1, with 2.4- to 2.9-fold differences (P less than 0.02). The total tachyzoite counts at 18 h decreased to 26-39% of those at 1 h in the presence of natural IgM antibody levels of greater than 0.8 (P less than 0.01), while the counts at 1 h consistently increased by 18 h in the absence of natural IgM antibodies. These results indicate that relatively high levels of natural IgM antibodies enhanced phagocytic and microbicidal activities of neutrophils against Toxoplasma. The enhancement was dose dependent, and was also weaker than that obtained with the same dilution of sera from individuals with chronic or acute infections. Live and dead tachyzoite counts in infected neutrophils suggested a quicker effect of natural IgM antibodies than IgG antibodies elicited by infection. PMID- 1641243 TI - Tryptophan metabolism and vitamin B6 nutritional status in patients with schistosomiasis mansoni and in infected mice. AB - Patients infected with Schistosoma mansoni showed an abnormal response to a test dose of tryptophan, with little increase in the urinary excretion of kynurenine, hydroxykynurenine, xanthurenic and kynurenic acids, N1-methyl nicotinamide, methyl pyridone carboxamide, 5-hydroxytryptamine or 5-hydroxyindoleacetic acid. In contrast to previous reports, this is different from the pattern of tryptophan metabolism seen in vitamin B6 deficiency. Furthermore, the patients' plasma concentrations of pyridoxal phosphate were within the reference range, and supplementation for 5 days with 20 mg vitamin B6/day did not affect tryptophan metabolism. Treatment with a single dose of Praziquantel resulted in a substantial restoration of normal tryptophan metabolism. In mice infected with S. mansoni there was a similar impairment of tryptophan metabolism, as shown by considerably reduced formation of 14CO2 after the administration of a tracer dose of [14C]tryptophan. Again, the administration of vitamin B6 supplements did not correct tryptophan metabolism in the mice. Treatment with Praziquantel resulted in substantial restoration of the production of 14CO2 from [14C]tryptophan. There was no evidence of vitamin B6 deficiency (as determined by erythrocyte aspartate aminotransferase activation coefficient) associated with infection in the mice, although there was a redistribution of pyridoxal phosphate between tissues, with a reduction in the concentration of liver, spleen and kidney, and an increase in skeletal muscle. PMID- 1641244 TI - A further model for temporal patterns in the epidemiology of schistosome infections of snails. AB - The prevalence of Schistosoma mansoni infections of Biomphalaria pfeifferi shows seasonal variation. Field data from Zimbabwe show annual ranges from 0 to 7%. In this paper a mathematical model of B. pfeifferi population dynamics and S. mansoni epidemiology is used as a framework for analysis of these patterns. Snail fecundity is a function of snail age and of temperature, and is apparently affected by other seasonal factors. The pre-patent period is dependent on temperature. Infection affects snail fecundity and mortality. Parameter values are derived from previous field and laboratory studies. The force-of-infection is estimated from the analysis of size-prevalence data. Using observed temperatures, model output agrees well with field data on snail abundance and prevalence of infection over a 14-month period. Seasonal variation in prevalence largely reflects variation in the pre-patent period and in snail population age structure. The possible role of seasonality in the force-of-infection is discussed. Prevalence patterns are not greatly affected by year-to-year differences in temperature. Significant seasonal variation in snail-man transmission rates is expected. PMID- 1641245 TI - A model for variations in single and repeated egg counts in Schistosoma mansoni infections. AB - Faecal egg counts are often used to measure Schistosoma mansoni infection, but the considerable variation between successive counts complicates their interpretation. The stochastic model described in this paper gives a description of observed egg counts in a population and can be used as a tool to gain an insight into the underlying worm load distribution. The model distinguishes between two sources of variation in egg counts: (1) variation caused by the difference in worm load between individuals, and (2) the variability of egg counts for an individual with a given worm load. Empirical data, single and repeated measurements, from surveys in five villages in Burundi and Zaire have been used to fit and validate the model. We have discussed possible mechanisms that explain the differences in estimated values between the villages. The model indicates that the expected number of eggs in a stool sample per S. mansoni worm pair is lower than suggested by autopsy data and that, possibly as a consequence of immunity, the inter-individual variation in worm loads decreases with age. PMID- 1641246 TI - Transport of isometamidium (Samorin) by drug-resistant and drug-sensitive Trypanosoma congolense. AB - The uptake kinetics of a 14C-labelled trypanocidal compound isometamidium chloride (Samorin, RMB Animal Health Ltd, UK) was measured in drug-resistant and drug-sensitive Trypanosoma congolense. It was established that drug uptake was significantly more rapid and quantitatively greater in drug-sensitive parasites. There was clear evidence that drug uptake in both the resistant and sensitive trypanosomes was by a specific, receptor-mediated process. This specific drug transport was energy-dependent, being sensitive to metabolic inhibition with SHAM/glycerol. Significant differences in drug transport were observed which could be correlated with resistance to isometamidium. The optimal pH for drug accumulation was lowered in the resistant trypanosomes; this finding, along with an observed change in specificity for the related compound homidium bromide, suggested that the specific receptor for isometamidium is altered in the resistant trypanosomes, possibly resulting in a reduction in drug uptake. In addition to these alterations in drug uptake, efflux of isometamidium also appears to occur in the resistant trypanosomes. Both a reduction in incubation temperature and metabolic inhibition increased the level of trypanosome associated isometamidium in the resistant parasites. This was in contrast to observations using drug-sensitive parasites. Furthermore, the addition of calcium flux-modulating agents to the incubation medium also resulted in an increase in accumulation by the resistant parasites. PMID- 1641247 TI - Preliminary characterization of the lipid and protein components of the protective surface membranes of a pentastomid Porocephalus crotali. AB - All instars of the pentastomid Porocephalus crotali, in the tissues of rat intermediate hosts and the lung of rattlesnake definitive hosts, are covered by a vesicular or stacked membranous secretory product which is synthesized in sub parietal cells (SPC) and channelled to the cuticle via multitudinous chitin-lined ducts. In rats this enveloping foam of vesicles survives for the duration of a cuticle. We have purified and partially characterized the lipid and protein composition of lamellate droplets from SPC of infective nymphs. Lipids in the droplets comprised a mixture of neutral and polar lipid classes with cholesterol being the major neutral lipid and phosphatidylcholine the dominant polar lipid. In addition, Triton X-114 phase separation of the protein component of droplets partitioned these into an aqueous phase (with a major band at 60 kDa), a detergent phase with two hydrophobic polypeptides (24 and 16 kDa) and an insoluble pellet containing several minor proteins and major bands at 31 and 107 kDa. Western blotting, with rabbit anti-lamellate droplet antiserum, strongly label only the 60 kDa and the two hydrophobic proteins. Significantly no proteins at all label with serum from infected rats from 50-150 days post-infection, a finding endorsed by indirect fluorescent antibody tests on sectioned V-VII stage nymphs. Possible immunomodulatory functions of SPC-derived surface membranes are discussed and, in this regard, they are compared with pulmonary surfactant, a product of alveolar Type II cells which lines all vertebrate lungs. PMID- 1641248 TI - Ectoparasite impacts on Gerbillus andersoni allenbyi under natural conditions. AB - To assess ectoparasite impact on individuals and populations of Gerbillus andersoni allenbyi under natural conditions, I addressed the following questions. Do ectoparasites affect their host fitness and, if so, how? Do ectoparasites affect host population level? Does this parasite-host interaction support the traditional concept of parasite evolution towards avirulence? For this purpose, host infestation, infection, survival, haematological indices, and physical condition were recorded. A field experiment which included manipulating host infestation while recording host survival was conducted to determine the causal relations between these variables. G. a. allenbyi was infested by 2 fleas (Synosternus cleopatrae and Stenoponia tripectinata), 5 mesostigmatid mites (Androlaelaps centrocarpus, A. hirsti, A. insculptus, A. marshalli and Hirstionyssus carticulatus), 1 tick (Rhipicephalus sanguineus), and 1 louse (polyplax gerbilli). Ectoparasite burden significantly reduced host survival and red blood cell indices (red cell concentration, haemoglobin concentration and haematocrit). Ectoparasite burden did not significantly affect white blood cell concentration. Gerbils were not infected by haemoparasites or gut helminths which potentially could cause anaemia. The causal relationship between S. cleopatrae burden and host survival was established by manipulation of host infestation. Both ectoparasite removal and initial level of infestation significantly affected host survival. Ectoparasites that caused anaemia were not associated with host physical condition (PC), measured as weight/length3. None of the red blood cell indices was correlated with host PC. These results suggest both that host PC was not affected by ectoparasite burden and that exsanguination leading to anaemia was the main effect of the ectoparasites. Ectoparasite pressure on the host population (based on the ectoparasite effects as estimated by statistical models, combined with dispersion of the infestation within the host population) changed seasonally and was greatest when host density was the highest. A large segment of the gerbil population was affected by ectoparasites during the entire year. An explanation for the evolution of parasite virulence, contrasting parasites that evolve towards increased virulence with parasites that evolve towards avirulence is presented. This classification is primarily based on whether parasite impact is equated with a higher efficiency of host exploitation, or whether it is a 'side effect' of parasite biology. PMID- 1641249 TI - Structure of the pinworm (Oxyurida: Nematoda) guild in the hindgut of the American cockroach, Periplaneta americana. AB - The pinworm (Oxyurida: Nematoda) guild in a laboratory colony of Periplaneta americana was investigated to answer the following questions. (1) Is guild structure stable with time? (2) Is there evidence of interaction among the species? (3) Is there evidence for niche diversification with respect to spatial distribution or developmental stage of host? Four species were found: Thelastoma periplaneticola, Thelastoma bulhoesi, Hammerschmidtiella diesingi and Leidynema appendiculatum; females of the first two could not be distinguished and they were lumped and referred to as Thelastoma sp.; 328 mid-instar hosts were dissected between September 1987 and February 1990, and the number of adult females of each pinworm species was recorded to investigate changes in guild structure through time. Seventy-five percent of hosts had Thelastoma sp., 62% had H. diesingi and 40% had L. appendiculatum; mean intensities were 6.5 (Thelastoma), 2.9 (H. diesingi) and 1.9 (L. appendiculatum). Relative numbers were stable with time and intensities of the species were similar whether they occurred alone in the host or in conjunction with other species. Thelastoma sp. and L. appendiculatum occurred together less often than expected and their numbers in individual hosts were negatively correlated. Both species occurred alone more often than expected. Surprisingly, H. diesingi and L. appendiculatum occurred together more often than expected. Intestines of 44 roaches were frozen in liquid nitrogen and divided into 5 equal sections to study longitudinal distributions of the species in the gut. Most L. appendiculatum and H. diesingi were found in the first, whereas most Thelastoma sp. occurred in the second segment. However, Thelastoma sp. dominated all segments of the gut. Worms were counted in 192 hosts belonging to 4 categories (early instar, late instar, adult male and adult female). Single species infections were more common in early instar hosts but there was no evidence that different species preferred different host stages. Modal distributions in male L. appendiculatum and T. bulhoesi suggest that these species may exhibit intraspecific interference competition similar to that observed in other pinworms. Such effects may be more important than interspecific effects in maintaining guild stability. PMID- 1641250 TI - Factors generating aggregation of Heligmosomoides polygyrus (Nematoda) in laboratory mice. AB - The importance of host heterogeneity in generating aggregation was investigated using Heligmosomoides polygyrus (Nematoda) in laboratory mice. Parameters of infection were compared between inbred and outbred mice, between primary and challenge infection protocols, and between gavage and natural exposure protocols, to investigate the relative effects of innate resistance, acquired resistance and behaviour, respectively. Heterogeneity in acquired resistance was identified as the most consistent factor leading to variability and aggregation of H. polygyrus numbers in mice. This hypothesis was supported in two experiments where groups of mice did not develop resistance to challenge infection (use of certain inbred strains of mice and immunosuppression with corticosteroids in the drinking water) and where variability in worm numbers after the challenge infection was comparable with that after the primary infection. Heterogeneity in host behaviour, particularly in behaviours enhancing skin contact with larvae, also was associated with increased heterogeneity in worm burden, though not as consistently as heterogeneity in acquired resistance. Surprisingly, worm burdens were not more variable in outbred compared with inbred mice. Our data suggest that the relative contributions of innate resistance, acquired resistance and behaviour in generating variable worm burdens are likely to vary spatially and temporally. PMID- 1641251 TI - Effects of cyclosporin A on the morphology and tegumentary ultrastructure of Hymenolepis microstoma in vivo. AB - Cyclosporin A (CsA) induced significant changes in parasite morphology when administered to mice infected with Hymenolepis microstoma. Gross morphological damage consisted of proglottis swelling and the formation of protuberances from the worm surface, visible with a low-power dissecting microscope, occurring most frequently in the posterior third of the strobila. Gross morphology and ultrastructure were examined further using scanning and transmission electron microscopy. Swollen proglottides exhibited areas covered in small pits and fissures (diameter approximately 1-2 microns) but it was not possible to establish the significance of this damage. The brush-border and distal cytoplasm appeared largely intact although some evidence of swelling of the basal membrane invaginations and possible fluid accumulation was seen in drug-treated TEM sections. The apparent oedematous condition of many of the proglottides from drug treated mice may indicate that CsA treatment mediates permeability changes in the worm surface membrane but the mechanisms by which this may occur remain to be elucidated. The effects of CsA on the morphology of H. microstoma correlate with the previously described anthelmintic activity of the drug against this parasite where CsA treatment dramatically reduces worm growth, retards migration into the bile duct and limits parasite survival. PMID- 1641252 TI - Moderate to heavy infections of Trichuris trichiura affect cognitive function in Jamaican school children. AB - A double-blind placebo trial was conducted to determine the effect of moderate to high loads of Trichuris trichiura (whipworm) infection on the cognitive functions of 159 school children (age 9-12 years) in Jamaica. Infected children were randomly assigned to Treatment or Placebo groups. A third group of randomly selected uninfected children were assigned to a Control for comparative purposes. The improvement in cognitive function was evaluated using a stepwise multiple linear regression, designed to control for any confounding variables. The expulsion of worms led to a significant improvement in tests of auditory short term memory (P less than 0.02; P less than 0.01), and a highly significant improvement in the scanning and retrieval of long-term memory (P less than 0.001). After 9 weeks, treated children were no longer significantly different from an uninfected Control group in these three tests of cognitive function. The removal of T. trichiura was more important than Ascaris lumbricoides in determining this improvement. The results suggest that whipworm infection has an adverse effect on certain cognitive functions which is reversible by therapy. PMID- 1641253 TI - On the distribution of a fluorescent ivermectin probe (4" 5,7 dimethyl-bodipy proprionylivermectin) in Ascaris membranes. AB - The distribution of the fluorescent ivermectin derivative (4" 5,7 dimethyl bodipy proprionylivermectin, referred to here as bodipy ivermectin) was studied in muscle vesicle membranes from the parasite Ascaris suum. Incubation in bodipy ivermectin, at concentrations greater than 1 ng/ml, produced a dose-dependent fluorescence in the vesicles. The level of fluorescence was not depressed (but increased) by prior incubation with 1 microM unlabelled ivermectin. This observation suggested that most of the bodipy ivermectin was free in the lipid phase of the membrane and not associated with a receptor. The trypan blue quenching technique showed that the bodipy ivermectin did not cross the membrane bilayer but remained in the outer monolayer. Lateral mobility of the probe in the membrane was studied using the fluorescence recovery after photobleaching (FRAP) technique. The lateral diffusion coefficient (DL) was 14.0 x 10(-10) cm2/s which was nearly three times faster than the lipid probe octadecanoyl-aminofluorescein in membranes from the same preparations; only 46% of the probe was mobile, showing that within a 1.2 microns radius the distribution of the bodipy ivermectin in the membrane was not homogeneous. These observations are used to suggest that: the site of action of ivermectin is located in the outer monolayer of the membrane (possibly on the Cl- channel); and that the speed of onset of action in isolated membrane preparations may be limited by diffusion in the membrane. PMID- 1641254 TI - Detection of teichoic acid antibodies in Staphylococcus aureus infections. AB - A commercially available agar gel diffusion (AGD) assay was used to investigate the teichoic acid antibody (TAA) response in 183 patients with proven Staphylococcus aureus (SA) infections. Two control groups were also investigated. One consisted of 100 hospitalized patients with a variety of medical and surgical conditions other than SA infection and the other consisted of 116 healthy hospital staff members. The sensitivity of the AGD assay varied markedly depending on the site of infection in the patients with proven SA infections. All patients with SA endocarditis developed positive TAA titres (greater than or equal to 1:4), although more than one third of these were initially negative. In patients with chronic osteomyelitis or septic arthritis, 41% had positive TAA titres, whereas no positive titres were detected in patients with acute osteomyelitis or septic arthritis. Lower rates of positive TAA titres were found in patients with deep abscesses (27%), pneumonia (14%) and post-operative infections (9%), but no positive titres occurred in patients with acute uncomplicated bacteremia, cellulitis or meningitis. In 100 hospitalized control patients, no positive titres were detected, and only 1 of 116 (0.9%) healthy hospital staff controls was positive. Suggested guidelines for the use of the AGD assay are discussed. PMID- 1641255 TI - Concurrent zidovudine-induced myopathy and hepatoxicity in patients treated for human immunodeficiency virus (HIV) infection. AB - Myopathy and hepatic toxicity are important complications of zidovudine (3'-azido 3'-deoxythymidine therapy) in patients infected with the human immunodeficiency virus (HIV) both may also occur in HIV infection in the absence of zidovudine therapy. We report 2 cases of myopathy caused by zidovudine, occurring within 16 wks of initiation of therapy, and a case of concurrent hepatic and muscle toxicity. In one case, electron microscopy demonstrated characteristic enlarged mitochondria with paracrystalline inclusions. This technique can distinguish the myopathies caused by either HIV or zidovudine. Both zidovudine-induced myopathy and hepatoxicity require discontinuation of the drug if severe. PMID- 1641256 TI - White sponge nevus presenting in the esophagus--case report and literature review. AB - White sponge nevus (WSN) is a rare inherited disorder which usually presents as non-painful white plaques primarily involving the buccal mucosa, gingiva and palate. Extra-oral lesions most often occur in the esophagus or anogenital area but almost invariably follow the development of typical buccal lesions. We present a non-familial case in which the first manifestation of the disease was in the esophagus in the absence of oral lesions. This sequence of events has not previously been reported in the literature. The cytohistological and electron microscopical appearances which allow the recognition and differentiation of WSN from other conditions presenting as esophageal white lesions are discussed. PMID- 1641257 TI - A fatal case of Vibrio vulnificus septicemia. AB - A fatal case of Vibrio vulnificus septicemia in a 60 yr old man is described. This man displayed many of the classical features seen in fulminant infections with this organism. The epidemiology of V. vulnificus infections is discussed in this report. PMID- 1641258 TI - Guillain-Barre syndrome and Campylobacter jejuni/coli. PMID- 1641259 TI - The introduction of selective biochemical requesting in a teaching hospital. PMID- 1641260 TI - The perinatal autopsy: a contemporary approach. AB - As autopsy rates in general hospitals decline, interest in the perinatal autopsy continues to rise, reflecting the emergence of a vigorous specialty growing in parallel with fetal medicine, prenatal diagnosis and clinical genetics. Perinatal autopsies are best carried out in tertiary centres which provide these services. Meticulous documentation, flexibility of technique, intelligent use of laboratory tests and wide systematic histopathologic sampling are emphasized. Microbiologic examination is of particular value when carried out by a laboratory having a special interest in genital tract and perinatal pathogens. Karyotyping must be selective if resources are to be conserved and is most productive when there are multiple malformations. Perinatal autopsy is not complete without examination of the placenta and significant lesions should be clearly distinguished from curiosities and from changes secondary to fetal death. The pathologist's wider contribution to perinatal medicine includes providing high quality data to epidemiology units and auditing committees, contributing to the multidisciplinary management of prenatally diagnosed fetal abnormalities, monitoring iatrogenic disease patterns and supporting the process of perinatal grief management. Special problems and diagnostic challenges are to be found when investigating sudden, unexplained intrauterine fetal death, hydrops, bone dysplasias and complicated multiple pregnancies. PMID- 1641261 TI - Age, site and distribution of subepithelial neurosecretory cells in the appendix. AB - The appearance of subepithelial neurosecretory cells (SNC) was investigated by studying completely sampled appendices of 50 children, adolescents and adults. The cells were demonstrated using lead hematoxylin, a selective stain for neurosecretory cells. Additional routinely sampled specimens were also studied for comparison. In children up to the age of 9 yrs only occasional SNC were found. After this age, however, SNC were present in most appendices and in greater numbers. The majority of SNC were located in the distal portion of the appendix, with only small numbers of these cells being present in the proximal segment. Occasional SNC-like cells were identified in the appendiceal submucosa in all regions of the appendix at all ages. This lends support to the hypothesis that a correlation exists between the presence of increased numbers of SNC, patient age and the site distribution of both acute appendicitis and appendiceal carcinoid tumors. PMID- 1641262 TI - Histological grading in breast cancer: interobserver agreement, and relation to other prognostic factors including ploidy. AB - Sections of neoplasms from 76 female patients with primary operable carcinoma of the breast were independently assessed by 2 pathologists for histological features and assigned a grade score. Relative disagreement rates between pathologists were estimated by use of a log-linear model and found to be similar to those reported by many other groups, but higher than that reported by acknowledged experts. Tumor grade was related to nuclear DNA content as measured by static cytometry, inversely related to oestrogen receptor status and provided some additional prognostic information but, in this small series of patients, did not correlate with short-term survival as closely as other prognostic indicators such as ploidy, tumor size or the extent of lymph node involvement. Patients with Grade III tumors had a particularly poor prognosis, however, there were few patients allotted to Grade III (poorly differentiated tumors), and survival differences between Grades I and II were small; in short-term followup, used alone, grading separated out only a small proportion of patients into useful prognostic groups. This preliminary study emphasizes the need for a careful approach to the use of grading of breast carcinomas in the routine histopathology laboratory. Demonstration of higher levels of interobserver agreement, or concordance with experts in the field, will be necessary before our grading can be incorporated into a prognostic index useful for patient management. PMID- 1641263 TI - Automation of prothrombin time on the Cobas Fara II centrifugal analyser. AB - The automation of the prothrombin time using Low Turbidity Australian Reference Thromboplastin on the Cobas Fara II centrifugal analyser is described. Initially this test was programmed as a 2-step technique to mimic the reference manual method. However, the wide variation of Cobas Fara normal control values obtained with several different batches of the reagent was unacceptable. Investigation of 1-step techniques resulted in dramatic changes in the normal control values. These changes would consequently alter reference values and affect International Sensitivity Index (ISI) and International Normalized Ratio (INR) determinations. This paper stresses the necessity to fully assess all methodology variables when evaluating new reagents. PMID- 1641264 TI - Test and teach. Number 67. Palisaded myofibroblastoma. (Intranodal hemorrhagic spindle cell tumor with "amianthoid" fibres). PMID- 1641265 TI - Post operative surveillance of human hydatidosis: evaluation of immunodiagnostic tests. AB - We investigated the kinetics of antibodies detected by indirect hemagglutination (IHA), IgE Elisa and immunoelectrophoresis (IEP) in patients with hydatid disease operated on and continuously followed in the pre-operative and post-operative periods. In the pre-operative phase the IgE Elisa test was found to be adequately sensitive (68.4%) compared with IHA (79%), with a ratio of IgE Elisa/IHA positivity of 87%, while IEP was positive in 55.3% of cases (IEP/IHA ratio = 70%). During post-operative follow-up IHA became negative late in patients who were cured (7 out of 11 were still positive after 4 yrs), whereas IEP and IgE Elisa became negative within 2 yrs of operation (apart from 1 patient with a persisting positive IgE Elisa 3 yrs later). However, IgE Elisa appeared clearly more sensitive in revealing postoperative recurrences (13 out of 13 patients had positive IgE Elisa, vs. 6 out of 13 IEP). PMID- 1641266 TI - Two new anti-rat macrophage monoclonal antibodies. AB - There are relatively few monoclonal antibodies (MAbs) to rat monocyte/macrophages available. We describe here 2 new such antibodies. The first, 109.2, recognizes most rat monocyte/macrophages and all polymorphs. The antigen recognized by this antibody is upregulated by 15 mins exposure to PMA (Phorbol myristate acetate) but down regulated by overnight exposure to LPS (lipopolysaccharide). It is probably an adhesion molecule and is likely to represent the rat equivalent of CD11b. The second antibody, 112.1, recognizes lysozyme in rat macrophages, particularly alveolar macrophages. In addition it also recognizes lysozyme in hen, rabbit and human macrophages. It also recognizes lysozyme in other tissues such as Paneth cells and proximal renal tubular cells. PMID- 1641267 TI - Development of an enzyme immunoassay to detect antibody to Chlamydia pneumoniae strain TWAR and its application in a limited seroepidemiological survey. AB - A non-competitive enzyme immunoassay (EIA) was developed to detect IgG antibody to the recently-described species Chlamydia pneumoniae strain TWAR. Purified elementary bodies of the organism were used as capture antigen. Cross-reacting antibody to Chlamydia trachomatis was detected in the assay by running a parallel EIA for IgG antibody to C. trachomatis. The C. pneumoniae assay was validated by comparing the results on 60 selected sera with those obtained with the microimmunofluorescence test. The comparison indicated that the EIA had a sensitivity of 88%, specificity of 100% and overall correlation with micro immunofluorescence of 93%. The assay was applied to 352 sera from 3 populations within Australasia in a limited survey to determine the extent of exposure to this organism. Prevalence rates of up to 55% were found, suggesting that a significant amount of respiratory disease in the region may be due to C. pneumoniae strain TWAR. PMID- 1641268 TI - Comparison of Roche blood culture bottle with an in-house conventional blood culture system. AB - A comparison was made of the in-use performance of an in-house broth blood culture in a general hospital during 8 mths in 1988 with that of a commercial biphasic culture (BCB system, Roche Products Pty Ltd, Sydney) for the corresponding period in 1989. The clinical services and the number of blood samples tested were comparable. The yields of organisms after 48 hrs incubation were similar in both systems. Staphylococcus aureus showed up 3 times as often after 24 hrs incubation in the conventional system as in the BCB system. Agitation of the BCB facilitated macroscopic detection of growth in the initial 24 hrs incubation. PMID- 1641269 TI - Variability of respiratory system compliance in mechanically ventilated infants. AB - We measured respiratory flow, volume by integrated flow, and airway pressure in four mechanically ventilated infants. Compliance of the respiratory system (Crs) was measured by the multiple occlusion method. Airway occlusion and release were achieved by a balloon in an occlusion valve between the endotracheal tube and a pneumotachometer, all connected in series with the respirator circuit. Values of Crs varied greatly due to changes in mean airway pressure (MAP). The Crs increased with the elevation of MAP on some occasions and decreased on others. Values of Crs also varied corresponding to different occlusion pressures for individual levels of MAP. Thus Crs changed continuously, even within a single respiratory cycle. The observed variability in Crs was explained by the following mechanism: a pressure-volume (P-V) loop of tidal ventilation moves its position within the pressure-volume diagram and changes shape due to variations of the ventilator settings. In some infants the lungs were ventilated in the range of the linear portion of the P-V diagram while in others they may have been ventilated on the flattened portion. Some patients had convex expiratory P-V curves even with low pressure swings during tidal ventilation. PMID- 1641270 TI - Nonlinear pressure/volume relationship and measurements of lung mechanics in infants. AB - We examined the effects of within-breath changes in compliance (C) upon the accuracy of measurements of compliance and resistance (R) by linear regression analysis and by Mead and Wittenberger's method. These effects were illustrated by a computer model and by lung models with linear and nonlinear pressure/volume relationships, and were also studied in 14 normal spontaneously breathing premature infants (mean +/- SD, BW 1,290 +/- 200 g, GA 29.9 +/- 2.7 weeks, age 7.4 +/- 2.1 days). Flow was measured by pneumotachography and tidal volume was derived as digitally integrated flow, and transpulmonary pressure as airway minus esophageal pressure. We found that C and R calculated from the equation of motion is accurate only if C and R remain constant throughout the respiratory cycle. Calculated compliance depends more on C at the end than at the beginning of inspiration. A decreasing C leads to underestimation or R, while an increasing C leads to an overestimation of inspiratory R. Calculated total R may be accurate, but with low r values for measurement points. Mead and Wittenberger's method and the regression method are similarly affected by changing C; however, since the regression method is based on many more measurement points and therefore allows the detection and analysis of within-breath changes of C and R, it is less prone to erroneous results secondary to signal artifacts than Mead and Wittenberger's method. PMID- 1641271 TI - Estimation of arterial carbon dioxide by end-tidal and transcutaneous PCO2 measurements in ventilated children. AB - Simultaneous measurements of arterial, end-tidal, and transcutaneous carbon dioxide (PaCO2, PetCO2, PtcCO2, respectively) were obtained in 134 children receiving mechanical ventilation (ages, 2 days to 16 years; mean, 2.5 years). The mean +/- SD PetCO2 bias (PaCO2 - PetCO2) was 3.4 +/- 6.6 mmHg. When the PetCO2 bias was plotted against the PaO2/PAO2 ratio, a change in the scatter was obvious at about 0.3. The PetCO2 bias for patients with PaO2/PAO2 under 0.3 was 7.8 +/- 7.3 mmHg compared to 0 +/- 3.4 in patients with PaO2/PAO2 above 0.3 (P less than 0.001). PetCO2 differed significantly from PaCO2 (P less than 0.001) only for patients with PaO2/PAO2 under 0.3. The slope (PaCO2 versus PetCO2) for these patients was 1.59, while the slope for patients with PaO2/PAO2 above 0.3 coincided with the line of identity (1.00). The mean +/- SD PtcCO2 bias (PaCO2 - PtcCO2) was -1.3 +/- 7.2 mmHg. Skin perfusion was recorded at the area close to the transcutaneous CO2 monitor electrode and was defined as normal when capillary refill was below 3 seconds. The PtcCO2 bias for patients with normal skin perfusion was -0.2 +/- 5.4 mmHg (P = 0.73) compared to -4.1 +/- 9.9 for patients with decreased skin perfusion (P = 0.01). The slope of PtcCO2 against PaCO2 was closer to identity in patients with normal skin perfusion (1.17) than in patients where it was decreased (slope, 1.40). We suggest that PaCO2 estimation by both PetCO2 and PtcCO2 is sufficiently precise and reliable for clinical use in critically ill children. Certain limitations stem from the nature of the techniques.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641272 TI - Mucoid Pseudomonas aeruginosa is a marker of poor survival in cystic fibrosis. AB - The aim of this study was to assess the prognostic significance of mucoid and non mucoid isolates of Pseudomonas aeruginosa (muPs and non-muPs) from the sputa of patients with cystic fibrosis (CF). Eighty-one children with CF who coughed up sputum daily were recruited and followed over 12 months with frequent sputum cultures. At the end of this observation period they were classified to one of three age-matched groups. In 50 mPs was isolated on one or more occasions; 19 grew non-muPs but not muPs, and 12 grew no isolates of Ps aeruginosa. These 81 children and adolescents were followed for a further 8 years or until they died. Twenty-one (42%) of the muPs patients died compared with two (11%) of the non muPs and one (8%) of the no Ps patients (P less than 0.01). Stepwise regression indicated that forced expiratory volume in 1 second (FEV1) had the main predictive effect but that age, Shwachman score and muPs also had a predictive effect. Identification of mucoid forms of Ps aeruginosa is an unfavorable prognostic factor but the isolation of non-mucoid strains does not appear to be any more important than the isolation of other common respiratory pathogens. PMID- 1641273 TI - Dexamethasone therapy for bronchopulmonary dysplasia: improved respiratory mechanics without adrenal suppression. AB - The purpose of the present study was to examine the pattern of changes in respiratory system mechanics induced by dexamethasone (Dex) in infants with bronchopulmonary dysplasia (BPD) and to determine whether dosages that produce these changes induce adrenal suppression. We examined mechanics in seven ventilator-dependent premature infants (age, 33 +/- 4.8 days) with BPD, before and daily during Dex therapy. Dex (0.5 mg/kg/day) was given intravenously for 7 days unless complications necessitated early termination. Respiratory system resistance (Rrs) and compliance (Crs) were measured by the passive expiratory flow-volume technique during the course of dexamethasone therapy or until extubation. Adrenocorticotrophic hormone (ACTH) stimulation tests were done at baseline and following Dex therapy to evaluate adrenal function. Dex therapy caused a 77 +/- 18% increase in Crs (from 0.97 +/- 0.09 SEM mL/cmH2O to 1.6 +/- 0.16 mL/cmH2O; P less than 0.025) and a 33 +/- 5% decrease in Rrs (from 0.20 +/- 0.02 cmH2O/mL/s to 0.14 +/- 0.01 cmH2O/mL/s; P less than 0.01). Concurrently, ventilator rate, mean airway pressure, and FIO2 all decreased significantly (P less than 0.025). Extubation occurred later in infants with the lowest Crs and highest Rrs at baseline. At extubation, all Crs values were greater than 1.33 mL/cmH2O and Rrs values were less than 0.15 cmH2O/mL/s. Systolic blood pressure increased from 61 +/- 6.3 mmHg to 84 +/- 17 mmHg, 72-96 h after the start of Dex (P less than 0.025). There were no episodes of culture-positive sepsis. Neither basal nor ACTH-stimulated levels of cortisol were suppressed as a result of Dex therapy (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641274 TI - Transfusion-induced changes in the breathing pattern of healthy preterm anemic infants. AB - In order to evaluate the effects of transfusion on breathing pattern in growing, otherwise healthy, anemic preterm infants, we studied 14 infants whose mean +/- SD birthweight was 1,212 +/- 294 grams, gestational age 29.28 +/- 2.23 weeks and hematocrit 25.86 +/- 2.24%. At a mean postnatal age of 41.35 +/- 19.45 days 12 hour nocturnal (transthoracic impedance) pneumocardiograms were obtained 24 hours prior to and after transfusion with 10 mL/kg of packed red blood cells. Posttransfusion pneumocardiograms revealed significant reduction of periodic breathing, of apnea episodes with 11-15 second duration, of apnea density, and of heart rate. These findings indicate that transfusion with packed red blood cells significantly alters certain cardiorespiratory variables in anemic preterm infants. PMID- 1641275 TI - Measurement of bronchial responsiveness in young children: comparison of transcutaneous oxygen tension and functional residual capacity during induced bronchoconstriction and -dilatation. AB - Demonstration of an increased bronchial responsiveness in preschool children may support the diagnosis of asthma. Most young children cannot perform routine lung function tests. Transcutaneous PO2 (PtcO2) measurement has been applied successfully in young children, and changes in PtcO2 have been shown to correlate well with changes in forced expiratory volume in 1 second (FEV1) during bronchoprovocation testing with methacholine. PtcO2 is, however, an indirect measure of the effect of inhaled spasmogens. As functional residual capacity (FRC) can also be measured by helium dilution spirometry in preschool children, we compared PtcO2 and FRC during methacholine inhalation challenges and after inhaled terbutaline, in order to determine whether FRC is useful as a more direct measure of induced bronchoconstriction and -dilatation than PtcO2. We studied 41 allergic asthmatic children (mean age, 5.2 years) who underwent a methacholine bronchoprovocation test; 38 children received terbutaline 1 h after the final methacholine dose. The provocative concentration of methacholine that caused a 20% decrease of PtcO2 was determined, and changes in FRC and PtcO2 after each methacholine dose step were compared. Similarly, changes in PtcO2 and FRC before, and 15 and 30 min after, terbutaline were compared. All children had a drop in PtcO2 after increasing doses of methacholine; a 20% change was reached in 38 patients. Mean FRC values increased significantly but variably with increasing doses of methacholine, and changes in PtcO2 and FRC did not correlate. After terbutaline, PtcO2 increased slightly but significantly, and FRC again varied unpredictably. In a separate group of 11 children, the effect of terbutaline was assessed directly after the final methacholine dose, when significant bronchoconstriction was still present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641276 TI - Hypersensitivity pneumonitis in an infant. PMID- 1641277 TI - William T. Grant Foundation. Faculty Scholars Awards 1992. PMID- 1641278 TI - Head injury in very young children: mechanisms, injury types, and ophthalmologic findings in 100 hospitalized patients younger than 2 years of age. AB - Head injury in the youngest age group is distinct from that occurring in older children or adults because of differences in mechanisms, injury thresholds, and the frequency with which the question of child abuse is encountered. To analyze some of these characteristics in very young children, the authors prospectively studied 100 consecutively admitted head-injured patients 24 months of age or younger who were drawn from three institutions. Mechanism of injury, injury type, and associated injuries were recorded. All patients underwent ophthalmologic examination to document the presence of retinal hemorrhages. An algorithm incorporating injury type, best history, and associated findings was used to classify each injury as inflicted or accidental. The results confirmed that most head injuries in children younger than 2 years of age occurred from falls, and while different fall heights were associated with different injury types, most household falls were neurologically benign. Using strict criteria, 24% of injuries were presumed inflicted, and an additional 32% were suspicious for abuse, neglect, or social or family problems. Intradural hemorrhage was much more likely to occur from motor vehicle accidents and inflicted injury than from any other mechanism, with the latter being the most common cause of mortality. Retinal hemorrhages were seen in serious accidental head injury but were most commonly encountered in inflicted injury. The presence of more serious injuries associated with particular mechanisms may be related to a predominance of rotational rather than translational forces acting on the head. PMID- 1641280 TI - Variability in head circumference growth rate during the first 2 years of life. AB - The head circumference (HC) curves were plotted for a group of 415 healthy full term babies over the first 2 years of life. Two hundred ten (51%) of the cohort demonstrated HC variability, defined as an HC acceleration or deceleration of at least 1 centile curve for at least 2 months. Of these, the deceleration pattern was predominant (80.9%), and also frequently permanent (87%). The HCs of 3 (1.42%) of 210 infants with HC variability ended up with a deviation of 2 standard deviations or more from the mean. The onset of HC transition occurred from the mean age of 1.3 months, and the new curve had stabilized by age 13 months in 95% of the study group. Parallel changes occurred in body weight and body length in approximately 48% of the total cohort, but more frequently in the variable-HC group. The clinical interpretation of these findings is discussed. PMID- 1641279 TI - Neuroendocrine effects of toxic and low blood lead levels in children. AB - From 3 million to 4 million children in America have lead poisoning. This environmental toxin affects 1 in every 6 children younger than 6 years of age in the United States. The marked effects of lead toxicity on the central nervous system are well known, ie, lowering IQ and impairing memory, reaction time, and the ability to concentrate. Children are at greatest risk for the central nervous system effects of lead because the central nervous system is at its peak in development during the first few years of life. The negative correlation of stature and blood lead level (bPb) found in the National Health and Nutrition Examination Survey directed the authors to evaluate the possible neuroendocrine effects of this toxin in children. Twelve children were studied during toxic (greater than or equal to 40 micrograms/dL) and low bPb (less than 40 micrograms/dL). Classic provocative stimuli, L-dopa (15 mg/kg by mouth) and insulin (0.1 U/kg given intravenously), were used to determine human growth hormone (hGH) responses during toxic bPb and after chelation therapy in six of the subjects. An additional four subjects were studied during low bPb. In two patients LGH levels were determined every 20 minutes for 24 hours during toxic bPb. Thyroid-stimulating hormone and prolactin responses to thyrotropin-releasing hormone were also determined. All children studied showed growth retardation during toxic bPb. Mean peak hGH responses to provocative stimuli were lower during toxic bPb, but the responses were all within normal limits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641281 TI - Capillary recruitment for preservation of cerebral glucose influx in hypoglycemic, preterm newborns: evidence for a glucose sensor? AB - Changes in cerebral blood volume (CBV) were investigated by means of near infrared spectroscopy in 18 preterm newborns during treatment with intravenous bolus glucose. All newborns were breathing spontaneously, and their postnatal age was 2 hours. Blood glucose concentration ranged between 0.3 and 2.2 mmol/L. Cerebral blood volume began to decrease shortly after the glucose infusion was terminated, and steady state was obtained after approximately 3 minutes. The decrease in CBV averaged 0.15 mL/100 g (range 0.02 to 0.40 mL/100 g). Thereafter, CBV remained constant. Individual reductions in CBV were inversely related to the pretreatment concentration of glucose, whereas there was no relation between changes in CBV and alterations in blood gas values or in mean arterial blood pressure. It is suggested that previously unperfused capillaries are recruited to maintain the glucose transport into neurons of hypoglycemic, preterm newborns. The rapidity whereby vessels adjust to alterations in glucose levels indicates the existence of a cerebral glucose sensor. PMID- 1641282 TI - Value of cranial ultrasound and magnetic resonance imaging in predicting neurodevelopmental outcome in preterm infants. AB - In this prospective study, cranial ultrasound was performed to detect periventricular-intraventricular hemorrhage and periventricular leukomalacia in 33 preterm infants of less than 32 weeks' gestation. At 44 weeks postmenstrual age magnetic resonance imaging was performed to detect the stage of myelination. Neurodevelopmental outcome was assessed at 3 years of age in 31 children (2 children died in the first year of life). Significant correlations were found between neurodevelopmental outcome and ultrasound findings (chi 2 = 32.8; P less than .0001) and stage of myelination (chi 2 = 20.5; P less than .0005). To establish the criterion with the best predictive factor, multiple regression analysis was performed with outcome as dependent variable and periventricular intraventricular hemorrhage, periventricular leukomalacia, and stage of myelination as independent variables. It appeared that the detection of periventricular leukomalacia with ultrasound showed the best predictive factor for neurodevelopmental outcome. Routine magnetic resonance imaging at 44 weeks postmenstrual age should not be performed just for the purpose of predicting neurodevelopmental outcome more reliably. PMID- 1641284 TI - Is there compensated hypothyroidism in infancy? AB - The state-mandated newborn thyroid screening program may uncover infants who exhibit normal thyroxine (T4) levels with various degrees of hyperthyrotropinemia. To elucidate further the thyroid status, the basal metabolic rate (BMR) of 10 infants (7 boys, 3 girls; aged 9 to 63 days) was studied by indirect calorimetry. They were clinically euthyroid and healthy with no evidence of overt biochemical hypothyroidism (low T4, high thyroid-stimulating hormone [TSH]). Confirmatory testing indicated that all infants had normal serum T4 levels for age (mean +/- SD: 10.3 +/- 3.2 micrograms/dL). However, serum TSH levels varied from 2.3 to 99.2 microU/mL. In 4 infants (2 boys, 2 girls) the BMR was low (38.1 +/- 4.1 kcal/kg per day), while the other 6 patients (5 boys, 1 girl) demonstrated BMRs within the normal range (49.6 +/- 1.9 kcal/kg per day, P less than .001). The serum TSH levels were above 7.0 microU/mL among those infants with a low BMR, whereas the serum TSH levels were always below 6.0 microU/mL among the normometabolic infants. All infants who had a low BMR received thyroid therapy and promptly became normometabolic (BMR: 48.7 +/- 1.0 kcal/kg per day) with suppression of TSH levels (3.2 +/- 1.3 microU/mL) within 3 weeks of therapy, while their serum T4 levels remained within the normal range. The observed normalization of BMR in parallel to reduction of TSH levels following thyroid replacement therapy strongly suggests that these patients demonstrated a hypometabolic state, despite normal serum T4 levels. Therefore, the assessment of BMR may help define subclinical hypothyroidism in infancy in conjunction with a close monitoring of TSH concentration. PMID- 1641283 TI - Effect of an exchange transfusion on plasma antioxidants in the newborn. AB - The effect of an exchange transfusion on antioxidants in the plasma of newborns with rhesus hemolytic disease was studied. The antioxidant concentrations in donor blood were similar to normal adult values except for the lower vitamin C concentrations. Exchange transfusion decreased the newborns' iron and ferritin levels and increased their ceruloplasmin and transferrin (primary antioxidants) concentrations and latent iron-binding capacity. The changes in secondary antioxidant concentrations were variable; uric acid and thiols were stable, vitamin C and bilirubin fell, and vitamin E rose. The total peroxyl-radical trapping capacity of the secondary antioxidants did not change significantly. The fall in levels of thiobarbituric acid reactive substances, an index of lipid peroxidation, was related to the lower levels present in the donor blood. Exchange transfusion rapidly produced variable changes in the concentrations of prooxidant and antioxidant substances in plasma and may thus influence free radical metabolism in the newborn. PMID- 1641285 TI - Postneonatal vitamin B6-dependent epilepsy. PMID- 1641286 TI - Attitudes of expectant fathers regarding breast-feeding. AB - Fathers participate in choosing the feeding method for their newborns. However they traditionally have not been included in most breast-feeding education programs. To examine expectant fathers' attitudes and knowledge regarding breast feeding, we surveyed 268 men during the first session of their childbirth education classes at five private hospitals in Houston, Texas. The study population was 81% white, 8% black, and 6% hispanic. Ninety-seven percent (n = 259) of the total were married. Fifty-eight percent (n = 156) reported that their spouses planned to breast-feed exclusively; several significant differences existed between these men and those who reported plans for exclusive formula feeding. The breast-feeding group was more likely to believe breast-feeding is better for the baby (96% vs 62%; P less than .0001), helps with infant bonding (92% vs 53%; P less than .0001), and protects the infant from disease (79% vs 47% P less than .001). The breast-feeding group was also more likely to want their partner to breast-feed (90% vs 13%; P less than .0001) and to have respect for breast-feeding women (57% vs 16%; P less than .0001). Conversely, those in the formula feeding group were more likely to think breast-feeding is bad for breasts (52% vs 22%; P less than .01), makes breasts ugly (44% vs 23%; P less than .05), and interferes with sex (72% vs 24%; P less than .0001). The majority of both groups indicated breast-feeding was not acceptable in public (breast-feeding = 71%, formula feeding = 78%, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641287 TI - Passive smoking and middle ear effusion among children in day care. AB - One hundred thirty-two children who attended a research day-care center were studied to determine whether passive tobacco smoke exposure was associated with an increased rate of otitis media with effusion or with an increased number of days with otitis media with effusion during the first 3 years of life. Based on preliminary studies, a serum cotinine concentration of greater than or equal to 2.5 ng/mL was considered indicative of exposure to tobacco smoke. Otitis media with effusion was diagnosed using pneumatic otoscopy by nurse practitioners and pediatricians who reviewed the children's health status each weekday. The 87 children with serum cotinine concentrations greater than or equal to 2.5 ng/mL had a 38% higher rate of new episodes of otitis media with effusion during the first 3 years of life than the 45 children with lower or undetectable serum cotinine concentrations (incidence density ratio = 1.38, 95% confidence interval 1.21 to 1.56). The average duration of an episode of otitis media with effusion was 28 days in the children with elevated cotinine concentrations and 19 days in the children with lower cotinine concentrations (P less than .01). It is estimated that 8% of the cases of otitis media with effusion in this population and 17.6% of the days with otitis media with effusion may be attributable to exposure to tobacco smoke. PMID- 1641288 TI - Effect of discharge samples on duration of breast-feeding. AB - The breast-feeding patterns of 146 women who initiated breast-feeding during their hospital stay were evaluated to determine whether those women who received a hospital discharge package containing a manual breast pump breast-fed their infants for a longer period of time than did women who received a discharge package containing an infant formula. Women were randomly assigned to receive either a specially prepared pack containing a manual breast pump but no infant formula or a commercially available infant formula package. The women were interviewed in the hospital and by computer-assisted telephone interviews at 2, 4, 6, and 8 weeks postdischarge. Information obtained included infant-feeding practices, sociodemographic characteristics, and attitudinal data. Follow-up interviews were completed for nearly 85% of eligible women at each time period. Women who received a discharge pack containing a breast pump but no infant formula continued exclusive breast-feeding for a greater number of weeks (mean = 4.18 weeks) than did women receiving infant formula in their discharge package (mean = 2.78 weeks) (P less than .05). Also, women who indicated that ease of nighttime feeding was an important consideration were more likely to breast-feed over the entire 8-week period if they received the breast pump rather than infant formula (P less than .05). The conclusion is that an easily implemented, low-cost intervention, the inclusion of a breast pump in discharge packages, may increase the duration of breast-feeding. PMID- 1641289 TI - Comparison of the causes and consequences of prematurity and intrauterine growth retardation: a longitudinal study in southern Brazil. AB - A cohort of 5914 liveborns (99% of the city births) was followed up to the age of 4 years in Pelotas, southern Brazil. Besides the perinatal evaluation, the cohort children were examined again at mean ages of 11, 23, and 47 months. During each visit the children were weighed and measured and information on morbidity was collected. Also, multiple sources of information were used for monitoring mortality throughout the study. Of the babies with known gestational age, 9.0% were classified as intrauterine growth-retarded and 6.3% as preterm. Excluding those of unknown gestational age, 62% of low birth weight babies were intrauterine growth-retarded and 36% were preterm. Intrauterine growth retardation was statistically associated with maternal height, prepregnancy weight, birth interval, and smoking, whereas preterm births were associated with maternal prepregnancy weight and maternal age. Preterm babies had a perinatal mortality rate 13 times higher than that of babies of appropriate birth weight and gestational age and 2 times higher than that of intrauterine growth-retarded babies. Infant mortality rates presented a similar pattern, with the differentials being more pronounced during the neonatal than in the postneonatal period. In the first 2 years of life intrauterine growth-retarded children were at almost twice the risk of being hospitalized for diarrhea compared with appropriate birth weight, term children, while preterm children experienced only a slightly greater risk. For pneumonia, however, both groups of children were hospitalized significantly more than appropriate birth weight, term children. In terms of growth, despite their earlier disadvantage, preterm children gradually caught up with their appropriate birth weight, term counterparts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641290 TI - Maternal employment and the quality of young children's diets: empirical evidence based on the 1987-1988 Nationwide Food Consumption Survey. AB - Data from 442 children, aged 2 to 5, who were participants in the 1987-1988 Nationwide Food Consumption Survey, were examined to determine the effect of maternal employment on the quality of their diets. Diet quality was assessed by examining nutrient adequacy and nutrient overconsumption using the 3-day average of one 24-hour recall and 2 days of written diet records. To assess dietary adequacy, a mean adequacy ratio of the four nutrients (zinc, vitamin E, iron, and calcium) for which 30% or more of the children fell below 77% of the Recommended Dietary Allowances was constructed. Percent calories from fat and saturated fat, and intake of cholesterol and sodium were examined to assess overconsumption. Multiple correlation regression analysis was used to control for household income, maternal education and age, child's age, race, number of siblings aged 5 or younger, presence of male head of household, and number of meals eaten away from home. Maternal employment did not contribute significantly to the variation in any of the dietary variables. Although a number of dietary problems existed among the sample children, the variation in intakes of these nutrients was not directly related to maternal employment status. PMID- 1641291 TI - DNA diagnosis of central nervous system infection by Mycoplasma pneumoniae. AB - A nested polymerase chain reaction method for the detection of Mycoplasma pneumoniae was devised and applied to clinical samples. This system could detect 5 to 50 fg of the DNA from M pneumoniae and did not amplify the DNA from Mycoplasma genitalium. With this method, the sequence of this organism was detected successfully in cerebrospinal fluid samples from four of six patients and in serum samples from three of four patients with clinically and serologically confirmed mycoplasmal central nervous system infection. This strongly suggested the direct invasion of this organism into the central nervous system and the concomitant occurrence of mycoplasmaremia. The nested amplification method is considered to be simple, rapid, and sensitive without the use of radioisotopes, thereby being highly applicable as a useful tool in routine clinical laboratories for the preliminary detection and diagnosis of mycoplasmal infections, particularly in extrapulmonary cases. PMID- 1641292 TI - Treatment with interferon gamma versus interferons alfa and gamma in children with chronic hepatitis B. AB - Thirty-five children with chronic hepatitis B were randomly assigned to three groups: group 1 (n = 12), untreated; group 2 (n = 11), treated with 1 million units of interferon gamma per square meter of body surface (MU/m2), three times a week for 24 weeks; and group 3 (n = 12), treated with interferon alfa at a dose of 5 MU/m2, three times a week for 12 weeks followed by 1 MU/m2 of interferon gamma with the same schedule. At the end of the treatment (6th month), hepatitis B virus DNA was negative in 16.5% of the control group, in 9% of the children treated with interferon gamma, and in 16.5% of those treated with interferons alfa and gamma. No child had lost the hepatitis B e antigen by this time. No basal differences in the serum hepatitis B virus DNA concentration among the groups were observed. At follow-up (15th month), viral genome was negative in 25% of the untreated children, in 36% of the group treated with interferon gamma, and in 41.5% of the children who had received interferons alfa and gamma. Hepatitis B e antigen was negative in 25% of the children who belonged to groups 1 and 3 and in 27% of the children treated with interferon gamma only. These data suggest that interferon gamma does not have a powerful antiviral effect on chronic hepatitis B in children. However, it is well tolerated. PMID- 1641293 TI - Pediatric dermatology update. PMID- 1641295 TI - Medical Education in Transition: the report of the Robert Wood Johnson Commission on Medical Education: the Sciences of Medical Practice. PMID- 1641294 TI - Concave hymenal variations in suspected child sexual abuse victims. AB - The purpose of this study was to describe and analyze the characteristics of, and the clinical correlates to, concave hymenal variations in a large number of suspected child sexual abuse victims. Thirteen hundred eighty-three female child and adolescent suspected sexual abuse victims were comprehensively evaluated. Photocolposcopy was used for the anogenital examinations. Concave hymenal variations were found in 174 patients (12.6%). Sixty-one (35.1%) were anterior. Of these, 40 (65.6%) were curved and smooth, and 21 (34.4%) were angular and/or irregular. One hundred (57.5%) were posterior/lateral. Of these, 33 (33%) were curved and smooth, and 67 (67%) were angular and/or irregular. Thirteen patients (7.5%) had multiple hymenal concavities. Posterior/lateral location was associated with penile-vaginal contact (P = .004), penetration (P = .006), stranger perpetrator (P = .032), hymenal rim narrowing (P less than .001), and posterior fourchette abnormality (P = .049). Angular and/or irregular features were associated with penile contact (P = .005), vaginal contact (P = .035), penile-vaginal contact specifically (P less than .001), penetration (P = .046), abnormal general physical examination (P = .018), and hymenal rim narrowing (P less than .001). Logistic regression analysis demonstrated that age-specific prevalence trends for posterior/lateral (P less than .001) and angular and/or irregular (P = .011) concavities were consistent with acquired anatomic findings. An interobserver exercise with five "blinded" raters evaluating photographs of 49 patients showed significant agreement among observers in sorting posterior/lateral and angular concavities into the diagnostic categories "suggestive of trauma" and "trauma."(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641296 TI - Managed care. PMID- 1641297 TI - Managed care. PMID- 1641298 TI - Serum enzyme monitoring in asthma patients. PMID- 1641299 TI - Serum enzyme monitoring in asthma patients. PMID- 1641300 TI - Baby's first spring water. PMID- 1641301 TI - Physicians' interactions with pharmaceutical companies. PMID- 1641302 TI - Recognizing the identifiers of child abuse as a syndrome. PMID- 1641303 TI - Faces of psychology. PMID- 1641304 TI - [MR imaging of intraocular lesions--a comparison with CT]. AB - Thirty-two intraocular lesions were studied with magnetic resonance (MR) imaging and computed tomography (CT). These lesions included retinoblastoma (n = 11), uveal melanoma (n = 6), metastatic choroidal tumor (n = 3), choroidal hemangioma (n = 2), retinochoroiditis (n = 6) and Coats' disease (n = 4). MR imaging was superior to CT in the depiction of intraocular masses and retinal detachment. Gd DTPA enhanced MR imaging was more useful than contrast enhanced CT in evaluating the contrast enhancement of intraocular tumors. Differential diagnosis of intraocular tumors was difficult with both MR imaging and CT. Intratumoral calcification was noticed on CT in nine cases of retinoblastoma. It was concluded that MR imaging, including contrast enhancement study, is more useful than CT in the evaluation of intraocular lesions, except for calcification, and contrast enhanced CT may be unnecessary in the diagnosis of intraocular lesions. PMID- 1641305 TI - [Evaluation of cleft lip and palate by computed tomography with 2 mm thin slice scanning--Part 2]. AB - Computed tomography was performed on 104 patients of cleft lip and palate with continuous 2 mm slice scanning. The type of hard palate was classified into 3 groups, as normal, hypoplasia and aplasia, depending on its developmental degree. The shape of alveolus was also grouped into 3 groups as circular, triangular and asymmetric forms for the evaluation of the maxillary development. The hard palate development correlated with the shape of the alveolus, the diameter of maxillary and mandibular bone, and frequency of sinusitis and otitis media. Evaluation of the hard palate by thin slice scanning is useful in presumption of future facial development. PMID- 1641306 TI - [Evaluation of the internal mammary nodes by lymphoscintigraphy and ultrasonography in patients with breast cancer]. AB - The efficacy of lymphoscintigraphy and ultrasonography was evaluated in the detection of internal mammary lymph node (IMN) metastases in patients with breast cancer. On histological examination of IMN, 10 patients had metastases (positive group) and 47 did not (negative group). On lymphoscintigraphy, lack of uptake in the parasternal region of the affected side was classified as abnormal. The frequency of this abnormal finding was not significantly different between both groups. On sonography, the thickness of the sonolucent internal mammary area was measured. The thickness of the affected side was 6 mm or more in two patients of the positive group and only one of the negative group. A thickness of over 6 mm on the affected side was statistically significant (p less than 0.05). The difference in thickness between the affected side and the healthy side was 3 mm or more in four patients of the positive group, and was less than 3 mm in all patients of the negative group. A difference in thickness of more than 3 mm between the two sides was extremely significant (p less than 0.001). In conclusion, sonography is valuable in detecting IMN metastases, while lymphoscintigraphy is not useful. Sonography is recommended as an efficient diagnostic modality for IMN metastases. PMID- 1641307 TI - [The biphasic response of hepatic arterial blood flow caused by vasoactive substances--an experimental study in dogs]. AB - In ten male mongrel dogs, blood flow was measured in the common hepatic artery (CHA), portal vein (PV) and liver tissue before and after the injection of vasoactive substances: angiotensin II (1.0 micrograms/kg), prostaglandin F2 alpha (1.0 micrograms/kg) and vasopressin (0.1 Unit/kg), under observation of the systemic circulation. Each injection caused a biphasic response in CHA blood flow, an initial decrease followed by a marked increase, while PV blood flow decreased. Liver tissue blood flow was reduced just after injection, but soon returned to a normal level. The duration of action was the shortest with prostaglandin F2 alpha and the longest with vasopressin. In using vasoactive substances in pharmaco-angiography, it is important to consider the biphasic response in CHA blood flow as well as the duration of action of these substances. PMID- 1641308 TI - [A clinical study of biliary endoprosthesis using an expandable metallic stent- evaluation of early results]. AB - Self-expandable metallic stents were used to relieve biliary obstruction in 58 patients. Fifty-three of 57 patients with malignant obstruction were treated with EMS after radiotherapy. A percutaneous approach was employed in all patients without severe complications. Insertion of EMS was successful in all cases. Within one week of EMS placement, all stents expanded to at least 90% of their original diameter, with the caliber of the bile duct always smaller than that of the EMS due to ischemic edema of the mucosa. In fifty-one of 58 patients, the external biliary drainage catheter could be removed. Cholangioscopy revealed that epithelium covered the EMS from the early phase after placement, enabling the EMS to become a physiological endoprosthesis in the bile duct. Rapid re-obstruction after EMS placement had two mechanisms: reactive obstruction and rebound obstruction, to avoid which adequate therapy to reduce the volume of the tumor is required. Also it is necessary to continue external drainage for at least two weeks after EMS placement. For the management of biliary obstruction, EMBE combined with radiotherapy is a promising treatment modality, with encouraging early results obtained. Further studies will determine the role of EMS in the treatment of patients with non-operable biliary obstructions. PMID- 1641309 TI - [Radiation therapy of intracranial germinoma]. AB - The appropriate radiation dose and field for the treatment of intracranial germinoma were investigated in 33 patients. Recurrences were observed in 4 cases treated with local field irradiation only, and all of them were recognized at the margin of the radiation field or under the dose (less than 25 Gy) area. This suggests that whole cranial irradiation (dose of 25 to 30 Gy) should be added even if the tumor is solitary. The effective dose for cerebrospinal dissemination appears to be 25-35 Gy, but prophylactic CNS irradiation seems unnecessary for patients who have not undergone surgical procedures. Changes in mental status were seen in 5 patients (26.3%). Doses of over 59 Gy may be related to this complication. PMID- 1641310 TI - [Combined treatment of invasive bladder cancer by intra-arterial infusion chemotherapy of cisplatin with or without other anticancer agents and concurrent radiotherapy--initial response and side effects]. AB - Fourteen patients with invasive bladder cancer were treated by bilateral internal iliac artery infusion of cisplatin, with or without other anticancer agents, and concurrent radiotherapy. Angiotensin II was simultaneously infused in 10 cases. Of the 14 patients, complete response and partial response were achieved in 9 (64%) and 3, respectively. Hematuria was controlled in all 8 patients, and pain was relieved in 3 of 4 patients. Side effects were observed in 8 patients: appetite loss in 8, nausea and/or vomiting in 7, and leukocytopenia in 6 patients, in 3 of whom radiotherapy had to be intermittent because of severe leukocytopenia (less than 2000/mm3). However, restoration of leukocytopenia occurred one week later. Thus, intra-arterial anticancer agents including cisplatin together with concurrent radiation may be one of the most effective therapies for invasive bladder cancer. PMID- 1641311 TI - [Results of radiation therapy of extrahepatic bile duct carcinoma]. AB - From January 1975 to August 1988, 40 patients with extrahepatic bile duct carcinoma were treated by external irradiation at Chiba University Hospital and the National Medical Center Hospital. Thirty-four patients (male: 20, female: 14) were evaluable. Eighteen patients were postoperative cases because the surgical margin was positive for tumor cells in the postoperative pathological examination; the other 16 were inoperable cases. Survival in postoperative and inoperable cases was not significantly different, with median survival times of 13.8 and 8.1 months, respectively. Survival in the recanalization-positive and negative-groups was significantly different (p less than 0.05) after irradiation, with median survival times of 13.5 and 6.0 months, respectively. Complications of therapy were recognized in 68% of all cases. They were mainly gastrointestinal symptoms such as nausea, vomiting, erosive gastritis and loss of appetite, but they were not severe. Distant metastasis was recognized in only 4 patients (10%): three had bony metastasis and one had supraclavicular and pulmonary hilar lymph node metastasis. Ninety percent of all cases died from hepatic failure or peritonitis carcinomatosa due to failure to obtain local control by external irradiation. A more effective modality of treatment is necessary to cure these patients. PMID- 1641312 TI - [Radiation management of retinoblastoma]. AB - Forty-five patients with retinoblastoma were treated at Keio University Hospital from 1970 to 1990. Thirty-two patients had unilateral lesions and 13 had bilateral lesions. Twenty-nine patients with unilateral and 12 with bilateral lesions underwent enucleation for advanced tumor. As a result, 3 patients with unilateral retinoblastoma and all patients with bilateral disease were treated with radiotherapy (40-50 Gy) combined with or without cryotherapy and/or photocoagulation. One patient with unilateral lesion treated with radiotherapy and chemotherapy had metastases at the first visit to our clinic and was excluded from this analysis. Among 16 eyes (15 patients) treated with radiotherapy, 6 eyes had recurrence and needed retreatment. Cataract occurred in 6 of 12 eyes and good vision was preserved in 5 of 10 eyes in which function could be evaluated. PMID- 1641313 TI - [Transcatheter embolization of the renal artery to treat massive retroperitoneal hemorrhage in long-term dialysis patients]. AB - Acquired cystic kidney disease (ACKD) and renal tumors often develop in long-term dialysis patients. In addition, rupture of the cysts leading to hemorrhagic shock can be another serious complication. There are few reports on transcatheter arterial embolization for retroperitoneal hemorrhage caused by cyst rupture in chronic dialysis patients. We report here three cases of massive retroperitoneal hemorrhage, caused by cyst rupture in two patients with ACKD and another patient with polycystic kidney disease during long-term dialysis, which were successfully treated by transcatheter arterial embolization. Embolization of the renal artery was performed with absolute ethanol and/or stainless steel coils. PMID- 1641314 TI - [Clinical evaluation of hepatic scintigraphy using 99mTc-GSA]. AB - Functional hepatic imaging was performed using 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA), a radiolabeled ligand that reacts specifically to the asialoglycoprotein receptor that resides at the plasma membrane of hepatocytes, in 21 patients: five with chronic active hepatitis (CAH), 14 with compensative liver cirrhosis (LC), one with chronic inactive hepatitis and one with acute hepatitis. The former two diseases were mainly investigated. Serial liver images were acquired at the rates of 10 sec/frame for 0-5 min and 2 min/frame for 6-30 min after the injection of 99mTc-GSA, and the images were compared with 99mTc phytate images in 2 patients with CAH and 11 with LC, and those with portal scintigrams using 123I-iodoamphetamine (IMP) in 3 patients with LC. The images using 99mTc-GSA were in better agreement with hepatic function than those using 99mTc-phytate, and with the findings of portal scintigraphy using 123I-IMP. LHL15 (liver/liver and heart radioactivities at 15 min after the injection of 99mTc GSA) correlated with the hepaplastin test (r = 0.978 in CAH, and r = 0.544 in LC), indicators of hepatic reserve. These results suggest that liver scintigraphy using 99mTc-GSA might be a useful method for evaluating liver function. PMID- 1641315 TI - [Experimental studies on metastases from an irradiated tumor]. AB - This study was carried out to determine the effect of irradiation of a tumor on the development of lung metastases. SANH, a spontaneous sarcoma, was isotransplanted in the right thighs of C3H mice which were either locally preirradiated (30 Gy: TBR) or non-irradiated. When the tumors had grown to 7 mm in diameter, they received 20-30 Gy of electron beams (RTx). The tumor-bearing legs were amputated at various tumor sizes, and the incidence of metastasis and number of lung nodules were compared in each treatment group. The incidences of metastases from 7 mm tumors in mice with regrowing tumors after RTx (30 Gy) and non-irradiated mice were 28% and 4%, respectively. When tumors grown in preirradiated legs were removed at 7 mm in diameter, the incidence of metastases (58%) was also enhanced by preirradiation of the tumor bed. Seven millimeter tumors that were growing in TBR legs and received RTx (20 Gy) developed a higher incidence (82%) and greater numbers of metastases than either the RTx or TBR groups. To determine the relationship between the interval of tumor bearing and development of metastases, tumors were removed at various intervals after tumor transplantation in 4 groups, namely, non-irradiated, TBR, RTx and TBR with 20 GyRTx. Lung metastases came later but increased steeply in mice given either TBR or RTx, compared with non-irradiated mice. Tumors growing in TBR and receiving RTx (20 Gy) developed many more metastases than any other group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641316 TI - [Endobronchial intraluminal brachytherapy for patients with tracheobronchial carcinoma with high dose-rate 192-Iridium remote afterloading method]. AB - Endobronchial intraluminal brachytherapy was conducted for 5 patients with tracheobronchial carcinoma using 192Iridium high dose-rate afterloading machine (microSelectron HDR) and guide tubes of 1.9 mm in outer diameter. Four patients with bronchial non-small cell carcinoma and one with tracheal adenocarcinoma were applied, and a dose of 6 Gy/Fr. at points 1 cm from the source once a week, and a cumulative dose of 18 Gy/3 Fr. was delivered. Guide tubes could be placed up to 3 tubes via the vocal airway, and new computer planning system could afford to calculate dose from independent lining of the source into optimization. This could be done with safety, and no remarkable acute side effects were observed attributable to this method. PMID- 1641317 TI - Review of research on critical thinking in nursing education. PMID- 1641318 TI - A review of literature on changing answers on multiple-choice examinations. PMID- 1641319 TI - Nontraditional students in higher education: a review of the literature and implications for nursing education. PMID- 1641320 TI - Qualitative research in nursing education. PMID- 1641321 TI - Nursing research related to educational re-entry for the registered nurse. PMID- 1641322 TI - Phosphorothioate primers improve the amplification of DNA sequences by DNA polymerases with proofreading activity. AB - Two thermostable DNA polymerases with proofreading activity--Vent DNA polymerase and Pfu DNA polymerase--have attracted recent attention, mainly because of their enhanced fidelities during amplification of DNA sequences by the polymerase chain reaction. A severe disadvantage for their practical application, however, results from the observation that due to their 3' to 5' exonuclease activities these enzymes degrade the oligodeoxynucleotides serving as primers for the DNA synthesis. It is demonstrated that this exonucleolytic attack on the primer molecules can be efficiently prevented by the introduction of single phosphorothioate bonds at their 3' termini. This strategy, which can be easily accomplished using routine DNA synthesis methodology, may open the way to a widespread use of these novel enzymes in the polymerase chain reaction. PMID- 1641323 TI - A rapid method for the isolation of DNA-binding proteins from purified nuclei of tissues and cells in culture. AB - We describe a rapid and general method for isolating DNA-binding proteins in high yield from purified nuclei of animal cells. The method has been tested for the isolation of a series of different DNA-binding activities including those of transcription factors PTF1 and SP1. The rationale consists of first preparing purified nuclei from tissue or cells in culture by centrifugation over sucrose cushions. A synthetic, biotinylated oligonucleotide bearing the binding site for the protein of interest is then added directly to nuclei resuspended in binding buffer. At the end of the binding reaction, nuclei are removed by centrifugation; and protein-DNA complexes present in the postnuclear supernatant are attached to streptavidin-agarose. Two rounds of DNA-affinity chromatography are carried out to yield highly purified preparations of DNA-binding proteins. PMID- 1641324 TI - The molecular structure of a 4'-epiadriamycin complex with d(TGATCA) at 1.7A resolution: comparison with the structure of 4'-epiadriamycin d(TGTACA) and d(CGATCG) complexes. AB - The structure of the complex between d(TGATCA) and the anthracycline 4' epiadriamycin has been determined by crystallographic methods. The crystals are tetragonal, space group P4(1)2(1)2 with unit cell dimensions of a = 28.01, c = 52.95A. The asymmetric unit consists of one strand of hexanucleotide, one molecule of 4'-epiadriamycin and 34 waters. The R-factor is 20.2% for 1694 reflections with F greater than or equal to 2 sigma F to 1.7A. Two asymmetric units associate to generate a duplex complexed with two drug molecules at the d(TpG) steps of the duplex. The chromophore intercalates between these base pairs with the anthracycline amino-sugar positioned in the minor groove. The double helix is a distorted B-DNA type structure. Our structure determination of d(TGATCA) complexed to 4'-epiadriamycin allows for comparison with the previously reported structures of 4'-epiadriamycin bound to d(TGTACA) and to d(CGATCG). The three complexes are similar in gross features and the intercalation geometry is the same irrespective of whether a d(CpG) or d(TpG) sequence is involved. However, the orientation of the amino-sugar displays a dependence on the sequence adjacent to the intercalation site. The flexibility of this amino-sugar may help explain why this class of antibiotics displays a relative insensitivity to base sequence when they bind to DNA. PMID- 1641325 TI - Transcription by an immobilized RNA polymerase from bacteriophage T7 and the topology of transcription. AB - It is often assumed that a polymerase moves along the template as it synthesizes RNA. However, a polymerase that tracks along a helical strand will generate a transcript that is entwined about the template. No such interlocking results if the polymerase is immobile and the template moves past it. Therefore we investigated whether immobilization inhibits the RNA polymerase of T7 bacteriophage using a hybrid protein, in which the polymerase is connected through a peptide linker to an immobilizing domain, which in turn was attached through an antibody to protein A covalently linked to plastic beads. Polymerase could be released by cleaving the linker with a protease, factor Xa. Comparison of the activity of the bound and free enzymes showed that immobilization reduced the rate of initiation about fivefold. However, when re-initiation was eliminated by removing excess template, immobilization was found to have little effect on the rate of elongation. Perhaps the untwining problem is sidestepped in vivo by immobilizing the polymerase. PMID- 1641326 TI - The Saccharomyces cerevisiae MGT1 DNA repair methyltransferase gene: its promoter and entire coding sequence, regulation and in vivo biological functions. AB - We previously cloned a yeast DNA fragment that, when fused with the bacterial lacZ promoter, produced O6-methylguanine DNA repair methyltransferase (MGT1) activity and alkylation resistance in Escherichia coli (Xiao et al., EMBO J. 10,2179). Here we describe the isolation of the entire MGT1 gene and its promoter by sequence directed chromosome integration and walking. The MGT1 promoter was fused to a lacZ reporter gene to study how MGT1 expression is controlled. MGT1 is not induced by alkylating agents, nor is it induced by other DNA damaging agents such as UV light. However, deletion analysis defined an upstream repression sequence, whose removal dramatically increased basal level gene expression. The polypeptide deduced from the complete MGT1 sequence contained 18 more N-terminal amino acids than that previously determined; the role of these 18 amino acids, which harbored a potential nuclear localization signal, was explored. The MGT1 gene was also cloned under the GAL1 promoter, so that MTase levels could be manipulated, and we examined MGT1 function in a MTase deficient yeast strain (mgt1). The extent of resistance to both alkylation-induced mutation and cell killing directly correlated with MTase levels. Finally we show that mgt1 S.cerevisiae has a higher rate of spontaneous mutation than wild type cells, indicating that there is an endogenous source of DNA alkylation damage in these eukaryotic cells and that one of the in vivo roles of MGT1 is to limit spontaneous mutations. PMID- 1641327 TI - Expression of Escherichia coli dam gene in Bacillus subtilis provokes DNA damage response: N6-methyladenine is removed by two repair pathways. AB - The dam gene of Escherichia coli encodes a DNA methyltransferase that methylates the N6 position of adenine in the sequence GATC. It was stably expressed from a shuttle vector in a repair- and recombination-proficient strain of Bacillus subtilis. In this strain the majority of plasmid DNA molecules was modified at dam sites whereas most chromosomal DNA remained unmethylated during exponential growth. During stationary phase the amount of unmethylated DNA increased, suggesting that methylated bases were being removed. An ultraviolet damage repair deficient mutant (uvrB) contained highly methylated chromosomal and plasmid DNA. High levels of Dam methylation were detrimental to growth and viability of this mutant strain and some features of the SOS response were also induced. A mutant defective in the synthesis of adaptive DNA alkyltransferases and induction of the adaptive response (ada) also showed high methylation and properties similar to that of the dam gene expressing uvrB strain. When protein extracts from B. subtilis expressing the Dam methyltransferase or treated with N-methyl-N'-nitro-N nitroso-guanidine were incubated with [3H]-labelled Dam methylated DNA, the methyl label was bound to two proteins of 14 and 9 kD. Some free N6-methyladenine was also detected in the supernatant of the incubation mixture. We propose that N6-methyladenine residues are excised by proteins involved in both excision (uvrB) and the adaptive response (ada) DNA repair pathways in B. subtilis. PMID- 1641328 TI - A combination of upstream and proximal elements is required for efficient expression of the mouse renin promoter in cultured cells. AB - Renin, a key enzyme controlling blood pressure, is produced mainly in the kidney. To identify the transcriptional regulatory elements of the mouse Ren-1c gene, the promoter regions were fused to the CAT reporter gene and transfected into embryonic kidney-derived 293 cells and four extrarenal cell lines, HeLa, HepG2, HT1080 and NIH3T3 cells. Transient transfection assay showed that sequences from 365 to +16 of the renin gene could direct transcription of the CAT hybrid gene only in 293 cells. Deletion analysis identified two transcriptionally active regions; the renin upstream-promoter element (RU-1 element; position -224 to 138) and the renin proximal-promoter element (RP-2 element; position -75 to -47). Although the RU-1 element functioned as an activator, depending on its orientation, it failed to trans-activate the renin promoter when the RP-2 element was deleted. By contrast, the proximal element alone exhibited a weak trans activator property. Gel shift assay identified RU-1 element-binding factors in both 293 and HeLa cells, whereas 293 cell-dominant factors were shown to bind only to RP-2 element. Therefore, both RU-1 and RP-2 elements were found to be necessary for efficient CAT expression from the renin promoter in 293 cells, suggesting that activation of the Ren-1c promoter requires combined action between cell type-dominant and ubiquitous nuclear factors. PMID- 1641329 TI - A comparison of several similarity indices used in the classification of protein sequences: a multivariate analysis. AB - The present work describes an attempt to identify reliable criteria which could be used as distance indices between protein sequences. Seven different criteria have been tested: i and ii) the scores of the alignments as given by the BESTFIT and the FASTA programs; iii) the ratio parameter, i.e. the BESTFIT score divided by the length of the aligned peptides; iv and v) the statistical significance (Z scores) of the scores calculated by BESTFIT and FASTA, as obtained by comparison with shuffled sequences; vi) the Z-scores provided by the program RELATE which performs a segment-by-segment comparison of 2 sequences, and vii) an original distance index calculated by the program DOCMA from all the pairwise dotplots between the sequences. These 7 criteria have been tested against the aminoacid sequences of 39 globins and those of the 20 aminoacyl-tRNA synthetases from E. coli. The distances between the sequences were analyzed by the multivariate analysis techniques. The results show that the distances calculated from the scores of the pairwise alignments are not adequately sensitive. The Z-score from RELATE is not selective enough and too demanding in computer time. Three criteria gave a classification consistent with the known similarities between the sequences in the sets, namely the Z-scores from BESTFIT and FASTA and the multiple dotplot comparison distance index from DOCMA. PMID- 1641330 TI - The application of Markov chain analysis to oligonucleotide frequency prediction and physical mapping of Drosophila melanogaster. AB - Here we compare several methods for predicting oligonucleotide frequencies in 691 kb of Drosophila melanogaster DNA. As in previous work on Escherichia coli and Saccharomyces cerevisiae, a relatively simple equation based on tetranucleotide frequencies can be used in predicting frequencies of higher order oligonucleotides. For example, the mean of observed/expected abundances of 4,096 hexamers was 1.07 with a sample standard deviation of .55. This simple predictor arises by considering each base on the sense strand of D. melanogaster to depend only on the three bases 5' to it (a 3rd order Markov chain) and is more accurate than the random predictor. This equation is useful in predicting restriction enzyme fragment sizes, selecting restriction enzymes that cut preferentially in coding vs noncoding regions, and in selecting probes to fingerprint clones in contig mapping. Once again, this equation well predicts the occurrence of higher order oligonucleotides, supporting our hypothesis that this predictor holds in evolutionarily diverse organisms. When ranked from highest to lowest abundance, the observed frequencies of oligomers of a given length are closely tracked by the predicted abundances of a 3rd order Markov chain. Through use of the dependence of oligomer frequencies on base composition, we report a list of oligomers that will be useful for the completion of a cosmid physical map of D. melanogaster. Presently, the library is such that it will be possible to construct large contigs using only 30 oligonucleotide probes to fingerprint cosmids. PMID- 1641331 TI - Thiophosphates in yeast U6 snRNA specifically affect pre-mRNA splicing in vitro. AB - A thorough mutational analysis of U6 RNA in combination with a functional reconstitution assay, revealed that three domains are important for U6 function in pre-mRNA splicing. In order to further analyze why these regions are so critical for splicing, we make use of phosphorothioate substituted U6 RNAs. Wild type U6 RNA was transcribed in vitro with T7 RNA polymerase in the presence of either phosphorothiate (alpha-S) ATP, GTP, UTP or CTP. The functionality of the transcripts was monitored by in vitro reconstitution. While substitution with alpha-S ATP, GTP or UTP blocked splicing, substitution with alpha-S CTP had little or no effect on splicing. We made use of this alpha-S CTP effect in an attempt to elucidate which phosphates in the U6 RNA molecule play a role in the first or in the second step of splicing. U6 mutants in which a change of an A, G or U to C does not have any significant effect on splicing were transcribed in the presence of alpha-S CTP. Observed effects on splicing thus have to be attributed to the presence of the thio-substituted phosphate group rather than the nucleotide change. The results of in vitro reconstitution give a clear answer for at least three phosphates; two of them play a role in the first step, while one of them is involved in the second step of splicing. PMID- 1641332 TI - hnRNP I, the polypyrimidine tract-binding protein: distinct nuclear localization and association with hnRNAs. AB - Many hnRNP proteins and snRNPs interact with hnRNA in the nucleus of eukaryotic cells and affect the fate of hnRNA and its processing into mRNA. There are at least 20 abundant proteins in vertebrate cell hnRNP complexes and their structure and arrangement on specific hnRNAs is likely to be important for the processing of pre-mRNAs. hnRNP I, a basic protein of ca. 58,000 daltons by SDS-PAGE, is one of the abundant hnRNA-binding proteins. Monoclonal antibodies to hnRNP I were produced and full length cDNA clones for hnRNP I were isolated and sequenced. The sequence of hnRNP I (59,632 daltons and pI 9.86) demonstrates that it is identical to the previously described polypyrimidine tract-binding protein (PTB) and shows that it is highly related to hnRNP L. The sequences of these two proteins, I and L, define a new family of hnRNP proteins within the large superfamily of the RNP consensus RNA-binding proteins. Here we describe experiments which reveal new and unique properties on the association of hnRNP I/PTB with hnRNP complexes and on its cellular localization. Micrococcal nuclease digestions show that hnRNP I, along with hnRNP S and P, is released from hnRNP complexes by nuclease digestion more readily than most other hnRNP proteins. This nuclease hypersensitivity suggests that hnRNP I is bound to hnRNA regions that are particularly exposed in the complexes. Immunofluorescence microscopy shows that hnRNP I is found in the nucleoplasm but in addition high concentrations are detected in a discrete perinucleolar structure. Thus, the PTB is one of the major proteins that bind pre-mRNAs; it is bound to nuclease-hypersensitive regions of the hnRNA-protein complexes and shows a novel pattern of nuclear localization. PMID- 1641333 TI - Phenol-treatment and a homologous pairing-assay. AB - Homologous pairing is a key step in homologous genetic recombination. In the early stage of trials for the identification of homologous pairing-promoting proteins from a fission yeast, Schizosaccharomyces pombe, we treated DNA products with phenol in the presence of a salt for the removal of tightly bound proteins from DNA before the assay, but we found that this treatment caused very efficient protein-independent double-strand formation from complementary single-stranded DNAs. Using an assay including the phenol treatment, we detected another species of apparent homologous pairing-promoting proteins in the nuclei, in addition to a homologous pairing-promoting protein consisting of three components which we reported previously. However, studies involving the use of an assay without the phenol-treatments revealed that the second one was not really a homologous pairing-protein. Thus, the protein-independent double-strand formation by phenol treatment in the presence of a salt could cause the erroneous identification of homologous pairing-promoting proteins. PMID- 1641335 TI - Expression and characterisation of the korB gene product from the Streptomyces lividans plasmid pIJ101 in Escherichia coli and determination of its binding site on the korB and kilB promoters. AB - A 0.5kb Spel-BclI fragment containing the pIJ101 korB ORF was cloned into pUC8 under the control of the lacZ promoter, creating pQR206. In vitro coupled transcription-translation of pQR206 identified a protein product of approximately 10kDa, which corresponds to the predicted molecular weight deduced from the korB sequence. pQR206 was used to express the 10kDa KorB protein in vivo in E. coli. Crude E. coli protein extracts containing KorB were shown to bind to a 0.8kb kilB fragment and a 0.5kb korB fragment in gel retardation assays. DNasel footprinting indicated that the DNA recognition sequence of the KorB protein lies within a 60bp protected region encompassing the kilB promoter and a 36bp region encompassing the korB promoter. PMID- 1641334 TI - Complex formation of nuclear proteins with the RNA polymerase I promoter and repeated elements in the external transcribed spacer of Cucumis sativus ribosomal DNA. AB - Complex repetitive structures are located downstream of the transcription initiation site in the intergenic spacer (IGS) of the rRNA genes in Cucumis sativus (cucumber). In order to show that these repetitive elements of the 5'external transcribed spacer (ETS) are probably involved in transcriptional regulation as protein binding sites DNA-protein binding assays were carried out. The same proteins that recognize two binding sites in the promoter region analysed (upstream binding element between -164 and -105, and core promoter between -41 and +16) show binding affinity to the complex structures of the 5'external transcribed spacer. These proteins also seem to interact with the single strands of the respective DNA regions suggesting an effect on transcriptional regulation while the DNA is transcribed and, therefore, is single stranded. Three proteins were isolated by affinity column chromatography; these proteins turned out to be much smaller (16, 22, and 24 kDa, respectively) than promoter and enhancer binding proteins in animal systems. Additionally, a 70-kDa protein could be characterized cooperating with a small segment of the repeated elements but not with the promoter. PMID- 1641336 TI - The cooperative interaction between two motifs of an enhancer element of the chicken alpha A-crystallin gene, alpha CE1 and alpha CE2, confers lens-specific expression. AB - An 84 bp element located between nucleotides -162 and -79 of the chicken alpha A crystallin gene exhibits lens-specific enhancer activity. Transient transfection experiments using 5' deletion and linker scanner mutants has indicated that the 84 bp enhancer element is composed of three motifs, alpha CE1 (-162 to -134), alpha CE3 (-135 to -121) and alpha CE2 (-119 to -99). Neither alpha CE1 or alpha CE3 motif alone can exhibit enhancer activity even when trimerized, whereas together they can direct some degree of lens-specific expression. alpha CE2 alone shows low transcriptional activity when trimerized. A combination of alpha CE1 with alpha CE2 exerts full lens-specific enhancer activity comparable with that of the 84 bp enhancer element, indicating that alpha CE1 and alpha CE2 motifs are sufficient to confer lens-specific expression. Transcriptional activation by these two motifs from a distance required the additional presence of either or both motifs adjacent to the beta-actin basal promoter. Gel shift experiments indicated that the alpha CE1, alpha CE2 and alpha CE3 motifs specifically bind nuclear proteins. alpha CE1 binds a protein predominantly present in lens cells, whereas alpha CE2- and alpha CE3-binding proteins differ between lens and lung cells. Mutations within the alpha CE1 and alpha CE2 motifs that failed to bind nuclear factors in vitro resulted in loss of transcriptional activation, indicating that these nuclear factors play a key role in controlling lens specific expression. PMID- 1641337 TI - Role of the conserved leucines in the leucine zipper dimerization motif of yeast GCN4. AB - Yeast GCN4 belongs to the class of eukaryotic transcription factors whose bZIP DNA-binding domains dimerize via a leucine zipper motif that structurally resembles a coiled coil. The leucine zipper contains 4-5 highly conserved leucine residues spaced exactly 7 residues apart that are located within the alpha helical hydrophobic interface between protein monomers. Here, we investigate the role of the four canonical leucines in the GCN4 leucine zipper by analyzing a series of mutated derivatives for their ability to activate transcription in vivo and to bind DNA in vitro. The GCN4 leucine zipper is surprisingly tolerant of mutations, with a wide variety of single substitutions at any of the four leucines including basic and acidic amino acids behaving indistinguishably from wild-type GCN4. Moreover, some derivatives containing two leucine substitutions display detectable though reduced function. These results indicate that other residues within the coiled coil are crucial for efficient dimerization, and they suggest that some eukaryotic transcriptional regulatory proteins lacking the conserved leucine repeat will dimerize through a structurally homologous motif. Interestingly, our results differ in several respects from those obtained by analyzing mutations in the GCN4 leucine zipper in the context of a lambda repressor-GCN4 zipper hybrid protein. These apparent differences may reflect a functional interrelationship between the leucine zipper and basic region subdomains for DNA-binding by bZIP proteins. PMID- 1641339 TI - Characterization of the spermidine-dependent, sequence-specific endoribonuclease that requires transfer RNA for its activity. AB - The spermidine-dependent, sequence-specific endoribonuclease (RNase 65) in mouse FM3A cells consists of protein and transfer RNA lacking its 3' terminus. In vitro properties of this enzyme were characterized using partially purified enzyme. The RNase 65 activity requires spermidine, which is not replaceable with spermine or Mg++. The enzyme cleaves an RNA substrate on the 3' side of the phosphodiester bond. The cleavage reaction has a temperature optimum around 50 degrees C and a pH optimum around 7.0. The optimum KCl concentration for the activity is around 10 mM. Relative cleavage efficiency of two differently folded RNA substrates with the common target sequence was analyzed at 37 degrees C and 50 degrees C. The results of this analysis suggest that unfolding of the target sequence is critical for recognition by RNase 65. Furthermore, in experiments using several point-mutated RNA substrates designed to form basically the same secondary structure as the wild type, one to three nucleotide substitutions in the target sequence all reduced cleavage efficiency. The RNase 65 activity is found only in cytosolic extracts, not in nuclear ones. Gel filtration analysis suggests that the native size of the endoribonuclease is approximately 150 kDa. PMID- 1641338 TI - The PCF1-1 mutation increases the activity of the transcription factor (TF) IIIB fraction from Saccharomyces cerevisiae. AB - PCF1-1 is a dominant suppressor of a tRNA gene A block promoter mutation (A19) in Saccharomyces cerevisiae. Transcriptional activation by PCF1-1 was examined in vitro using whole-cell extracts and purified factors derived from mutant and wild type strains. These experiments show that PCF1 is a general activator of RNA polymerase III (pol III) gene transcription. The transcription of all pol III genes analyzed to date, including type I and numerous type II genes, is increased 3-7 fold in mutant cell extracts. Single round transcription assays indicate that the PCF1-1 mutation increases the number of functional preinitiation complexes and suggest that this is achieved by increasing the intrinsic activity of the encoded product rather than its amount. Point mutations throughout the A block of the sup3-e gene and numerous B block mutations fail to abolish transcriptional activation suggesting that interactions between TFIIIC and the internal promoter are unaffected by PCF1-1. Moreover, TFIIIC purified from the mutant strain is incapable of conferring PCF1-1 transcriptional activity to a reaction in which the remaining components are wild-type. In contrast, the activity of the TFIIIB fraction is increased in PCF1-1 extracts and can reconstitute mutant levels of transcription when added to wild-type TFIIIC and polymerase. We conclude that PCF1 is a component or regulator of TFIIIB. PMID- 1641340 TI - Two promoter elements are necessary and sufficient for expression of the sea urchin U1 snRNA gene. AB - The essential elements of the sea urchin L. variegatus U1 snRNA promoter were mapped by microinjection of a U1 maxigene into sea urchin zygotes. Two elements are required for expression: a distal sequence element (DSE) located between -318 and -300 and a proximal sequence element (PSE) centered at -55. Removal or alteration of other sequences conserved in different sea urchin snRNA U1 genes, including deletion of all sequence between -90 and -273, did not affect the expression. Sequences around the start site were not required for expression. Deletion of nucleotides between the PSE and the start site resulted in initiation inside the U1 coding region, suggesting that the PSE determines the start site of transcription. There is no obvious similarity between the sequences required for the sea urchin U1 snRNA expression and the sequences required for the expression of other sea urchin snRNAs. PMID- 1641341 TI - Sequence and variability of the 5.8S and 26S rRNA genes of Pneumocystis carinii. AB - The sequence of the coding region of the rRNA operon of rat-derived Pneumocystis carinii has been completed, including the genes for 5.8S and 26S rRNA. These genes show homology to the rRNA genes of yeast, and an apparent group I self splicing intron is present in the 26S rRNA gene. Like a similar intron in the 16S rRNA gene, this intron is in a phylogenetically conserved region. Variation in the 26S rRNA sequence was noted between P. carinii organisms isolated from two different sources. PMID- 1641342 TI - Transfer RNA genes in the mitochondrial genome from a liverwort, Marchantia polymorpha: the absence of chloroplast-like tRNAs. AB - Twenty-nine genes for 27 species of tRNAs were deduced from the complete nucleotide sequence of the mitochondrial genome from a liverwort, Marchantia polymorpha. One to three species of tRNA genes corresponded to each of 20 amino acids including three species for leucine and arginine, two species for serine and glycine, and one for the rest of the amino acids. Interestingly, all tRNA genes were located in the semicircle of the liverwort mitochondrial genome except for the trnY and trnR genes. The region containing these tRNA genes was originally duplicated, and two trnR genes have diverged from each other. On the other hand, trnY and trnfM are present as two identical copies. The G:U and U:N wobbling between the first nucleotide of the anticodon and the third nucleotide of the codon permit the 27 tRNA identified species to translate almost all codons. However, at least two additional tRNA genes, trnl-GAU for AUY codon and trnT-UGU for ACR codon, are required to read all codons used in the liverwort mitochondrial genome. All of the identified tRNA genes are 'native' in liverwort mitochondria, not 'chloroplast-like' tRNAs as are found in the mitochondria of higher plants. This result implies that the tRNA gene transfer from chloroplast to mitochondrial genome in higher plants has occurred after the divergence from bryophytes. PMID- 1641343 TI - Characterization of the elongation factor 1-alpha gene of Rhynchosciara americana. PMID- 1641344 TI - Isolation and characterization of a restriction enzyme BspO4I from an alkalophilic bacterium. PMID- 1641345 TI - AspEI, a novel Eam11051 isoschizomer from Aureobacterium species recognizing 5' GACnnn/nnGTC-3'. PMID- 1641346 TI - Caenorhabditis cDNA encodes an eIF-4A-like protein. PMID- 1641347 TI - The nucleotide sequence of a mouse cDNA encoding the 80 kDa subunit of the Ku (p70/p80) autoantigen. PMID- 1641348 TI - Nucleotide sequence of the Rickettsia prowazekii greA homolog. PMID- 1641349 TI - Complete nucleotide sequence of the cosmid vector pWE15A. PMID- 1641350 TI - Conserved structural motifs within the N-terminal domain of TFIID tau from Xenopus, mouse and human. PMID- 1641351 TI - A simple and highly efficient procedure for rescuing autonomous plasmids from yeast. PMID- 1641352 TI - A reliable method for amplifying cDNA using the anchored-polymerase chain reaction (A-PCR). PMID- 1641353 TI - A new mouse embryonic stem cell line with good germ line contribution and gene targeting frequency. PMID- 1641355 TI - [The radioiodine-concentrating oncocytic thyroid carcinoma: a case report]. AB - A patient with radioiodine-positive metastases to bone and lung of an oncocytic thyroid cancer is reported. A left-sided thyroidectomy had been performed nine years earlier. Histologically it had been a large capsular Huerthle-cell adenoma with regressive changes without signs of malignancy. During a recent operation for a disc prolapse in the lumbar spine a metastasis of an oncocytic thyroid cancer was found. A radioiodine scan showed high accumulation of 131I in the thyroid region, the lung and the lumbar spine. The rare finding of radioiodine uptake in oncocytic cancer is discussed. PMID- 1641354 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1641356 TI - [Atypical scintigraphic appearance of an osteosarcoma. An explanation using x-ray and histologic findings]. AB - In a 10-year old girl with a telangiectasic osteosarcoma of the proximal right tibia, sequential bone scintigraphy with 99mTc-DPD showed the tumor as an atypical photopenic lesion in the osseous phase. Considering conventional radiographs, angiographic features and histologic aspects, possible explanations for this unusual finding are discussed. PMID- 1641357 TI - [The detection of inflammation and the formation of HAMA following the administration of monoclonal antibody BW 250/183]. AB - Experiences with the use of the 99mTc-labelled MAb BW 250/183 in the detection of inflammatory lesions are reported. In 160 of 354 investigated patients the results could be confirmed by other methods. The sensitivity (91%) and the specificity (82%) were very high for a diagnostic tool and were comparable with the results of other leukocyte scans as reported in the literature. The positive predictive value of the method was 93%. In 84 patients studied once and in 6 patients studied twice only one case of the latter group showed a positive HAMA response. It may be concluded that the detection of foci of inflammation with the 99mTc-labelled MAb BW 250/183 is of great diagnostic value and that its administration can be repeated without risk. PMID- 1641358 TI - [Radioimmunoscintigraphy and magnetic resonance tomography in the diagnosis of urinary bladder cancer]. AB - Magnetic resonance tomography is a method which is sufficiently precise to demonstrate morphological changes for tumor staging of carcinoma of the urinary bladder. The stage of the tumor was correct in 68 resp. 86% of the patients. The RIS shows organ and lymph node metastases and has the capability to differentiating between scar and tumor after transurethral resection. The local spread, especially the infiltration depth of the tumor, is not visible. In 90% of the patients a primary tumor was detected, only in 5 cases a false-negative and in 2 cases a false-positive finding was made. PMID- 1641359 TI - Diagnostic accuracy of 99mTc-anti-CEA immunoscintigraphy in patients with liver metastases from colorectal carcinoma. AB - 17 patients with 43 liver metastases from colorectal carcinoma were studied by immunoscintigraphy (IS) using a 99mTc-labelled monoclonal anti-CEA antibody (BW 431/26). Sensitivity and diagnostic accuracy were 21% for all liver lesions, but 47% considering the number of patients (at least one positive finding out of multiple metastases) and 77% in patients with a single metastasis. SPECT imaging did not improve sensitivity markedly in this series. There was no correlation with CEA serum levels. Liver metastases of intermediate size with moderate tumour necrosis seem to be favourable to IS. Major reason for the low sensitivity is the poor tumour-to-background ratio caused by high unspecific uptake of 99mTc labelled antibodies in the RES of the liver. At the moment, IS seems be only a supplementary method to conventional diagnostic procedures. PMID- 1641360 TI - [Clinical value of the ultrafast gradient echo sequence "Quickflash"]. AB - It is possible to develop faster sequences with 6 mT/m gradient field strength. However, the short gradient switch times which are advantageous for a better image contrast cannot be achieved. Using longer measurement times the influence of the preparation pulses is less dominant. The image quality of the quickflash is poorer than that of conventional SE and GE sequences. In some cases, especially for outline views and in the evaluation of Gd inflow into pathologic tissue or in restless patients, we use the quickflash in clinical routine. PMID- 1641361 TI - [Effect of intraperitoneal administration of sandoglobulin on peritoneal fluid IgG level in patients treated by standard peritoneal dialysis (SPD)]. AB - In 6 patients (PTS) treated with SPD for 369 patient weeks (ptw) we evaluated the influence of three intraperitoneal SI on the IgG concentration in the PE. The concentration of IgG was checked before, on 1-st, 3-rd day 2-nd and 3-rd week after SI. In the course of the following 229 ptw, we observed three episodes of peritonitis (PN) in two pts, while in the control period of 140 ptw no PN occurred. The concentrations in PE of opsonins (IgG, C3 complement, fibronectin) at the start of SPD shoved enormous individual differences and did not correlate with occurrence of PN in the follow-up. Intraperitoneal SI caused significant increase of IgG in PE, but only to the third day after infusion. Our preliminary results do not confirm the protective effect of intraperitoneal SI on occurrence of PN in SPD patients. PMID- 1641362 TI - [Hormonal and hemodynamic changes caused by whole body cooling in patients with rheumatoid arthritis]. AB - A limited number of experiments have shown that treatment of rheumatoid arthritis by means of cooling the entire body in cryogenic chamber reduces the pain in joints affected by inflammatory process and increases their mobility. The aim of the present thesis was to try explain the mechanisms responsible for the observed improvement of the patients' condition, and an investigation of the treatment's effect on selected hemodynamic indices. Tests were carried out on 63 patients with rheumatoid arthritis mainly in the 3rd and 4th stage of illness, all of whom had been treated for 14 days, once daily, by cooling the body for two-minute periods in cryogenic chamber with temperatures ranging from -110 degrees C to 160 degrees C, followed by kinesitherapy. It was demonstrated that after a single session in the cryogenic chamber, after 7 and 14 days the level of ACTH, cortisol and beta-endorphins in blood serum rises. The level of TSH, T4, T3, GH and 6-keto PGF1 alpha+, however, remains unchanged. The cryogenic chamber treatment does not affect the heart rate, arterial blood pressure nor the value of the left ventricle fractional shortening index and its ejection, neither does it cause of arrhythmias and ischemic changes of the heart. PMID- 1641363 TI - [Hypercalciuria and primary hyperparathyroidism in patients with kidney calculi. I. Hypercalciuria]. AB - In 1819 patients with active or non active respectively nephrolithiasis the following parameters were assessed: plasma level of calcium, phosphate, and uric acid and urinary excretion of calcium, phosphate, oxalate, uric acid and creatinine. These parameters were estimated after 5 days of diet containing 400 mg of calcium, 800 mg of phosphate, 100 mg of purines and 40 g of proteins. In 3/4 of all examined patients at least one lithogenic factor was present. More than 40% of patients showed presence of hypercalciuria. Among these patients in 68% renal in 17% absorptive and in 15% undefined hypercalciuria was diagnosed. Patients with active nephrolithiasis showed a similar frequency of hypercalciuria but more profound abnormalities of Ca P metabolism than patients with non active renal stone disease. PMID- 1641364 TI - [Hypercalciuria and primary hyperparathyroidism in patients with kidney calculi. II. Primary hyperparathyroidism]. AB - Among 1819 patients with renal stone disease 44 cases with primary hyperparathyroidism (p.h.p.) were diagnosed. In all cases the diagnosis of php was confirmed by histomorphological examination. In 34 patients with php solitary adenoma was found, in 5 patients an adenoma with concomitant hyperplasia of the parathyroid glands, in 2 patients hyperplasia and in 3 patients carcinoma of the parathyroid glands. Hypercalcemia was found in 86% of patients, while elevated plasma levels of PTH in 90% of patients with php. Not in all patients PTH secretion was entirely autonomous. No significant correlation was found between plasma levels of PTH and kind of pathology of the parathyroid glands as well as clinical feature of php respectively. PMID- 1641365 TI - [Doppler ultrasonography of arteries of the lower extremities]. AB - We examined 90 male nonsmokers aged 22 to 76, without any symptoms of arterial occlusive disease. They were in the I class of the NYHA classification. The subjects were divided into 2 groups according to age: group I 22-49, group II 50 76. The study was performed using an Acuson 128 with linear probe 5 MHz. We examined arteries of the lower extremities from external iliac artery to popliteal artery. On the B-mode image the diameter of the artery and wall irregularities were evaluated. Doppler spectra were evaluated according to 3 criteria. Doppler waveforms differed significantly between two groups. The third wave of spectrum (the diastolic wave toward the probe) was significantly lower in group II. This finding may be caused by decrease in vessel wall compliance in elderly patients. Moreover we found spectral broadening in the presence of atherosclerotic plaques (38% in group II). The authors' examination showed that Doppler sonography is useful in the evaluation of abnormality of an asymptomatic areas. Our study also indicated that subject's age has to be taken into consideration when Doppler waveforms are evaluated. PMID- 1641366 TI - [Personal experience with the diagnosis of peritonitis complicating a long-term program of peritoneal dialysis]. AB - Among 37 patients (pts) with irreversible renal failure treated in years 1980 1990 with chronic peritoneal dialysis there were 18 pts treated with continuous ambulatory peritoneal dialysis (CAPD) and 19 pts treated with standard intermitent peritoneal dialysis (SIPD). Mean incidence of peritonitis (P) was 1 episode per 9.0 patients-months. The important symptoms for early diagnosis of P were as follows: opacity of the peritoneal effluent (PE) and high (more than 50%) percentage of polynuclear cells in the smear of PE sediment. Positive results of PE culture were obtained only in 50% of P episodes in years 1980-1985, mostly in pts treated with CAPD (17/21 pts). In the period of 1986-1990, in pts treated mostly with SIPD (15/16 pts), positive results were obtained in 80% of P. Improvements of bacteriological diagnosis of P, especially in pts treated with CAPD, were discussed. Prophylactic cultures of PE were found to be of no value. PMID- 1641367 TI - [Therapeutic use of the method of water immersion in a patient with ascites in uncompensated cirrhosis of the liver]. AB - Water immersion was used as the treatment method in a patient with ascites caused by liver cirrhosis resistant to therapy. Application of water immersion caused only a short improvement; it was probably connected with the shortterm natriuretic effect. The joint effect of a diuretics and of the water immersion was beneficial. PMID- 1641368 TI - The development of vascular supply of normal rat prostate during the sexual maturation: an angiographic study. AB - Vascular distribution of small blood vessels and capillaries using India ink angiography was studied in normal rat prostate from puberty up to full sexual maturation. The study included both macroscopic observation of the lobular vascular irrigation and the histological assessment of the periacinar capillary network. The topographical distribution of the main prostate branches was found to be different among the rat prostate lobes. The ventral lobe seems to be better irrigated than the dorsal one. The former being supplied by two parallel vascular systems, one irrigating the median two-thirds of the ventral lobe, whereas the remaining external one-third was found to be conjointly irrigated from the pericapsular branches of the fat pads. The blood vessels of the dorsal and lateral lobes emerged radially from a periurethral circle, with the dorsal branches ending blindly in the connective tissue of the pelvic cavity, whereas the lateral prostate was also conjointly irrigated by a dual vascularization from the pericapsular fat pad and the periurethral circle branch. The histological study revealed quantitative differences between the periacinar capillaries of both ventral and dorsal lobes. The capillary density was found to be age dependent and directly proportional to the acinar size. Small acini were less well irrigated by capillaries than were the larger ones. The number of capillaries per acinar area increased progressively toward the maturation (day 90); thereafter, their number remained constant. Both prostate lobes showed identical patterns. The heterogeneous vascular networks among the rat prostatic lobes might offer an additional clue for their distinctive morphophysiological characteristics, which most probably play a role in various pathogenetic processes. PMID- 1641369 TI - Response of rat and human prostatic cancers to the novel 5 alpha-reductase inhibitor, SK&F 105657. AB - The response of two androgen-responsive rat prostatic cancers (i.e., Dunning R 3327 H and G sublines) and one androgen-responsive human prostatic cancer (i.e., PC-82) to the 5 alpha-reductase inhibitor, SK&F 105657, was tested in vivo. SK&F 105657 was administered orally twice a day at a dose of 25 or 50 mg/kg/dose. The rat R-3327 G tumor and the human PC-82 tumor have a low to undetectable level of tissue 5 alpha-reductase activity and both responded to SK&F 105657 treatment with a reproducible inhibition of tumor growth. Associated with this antitumor effect was a major decrease (i.e., greater than 70%) in tissue dihydrotestosterone (DHT) content in both tumors. By contrast, the rat R-3327 H prostatic cancer has a much higher level of tissue 5 alpha-reductase activity, and neither tumor DHT content nor growth of the tumor was inhibited by treatment with SK&F 105657. Drug treatment of rats bearing R-3227 H tumors resulted in a similar reduction in the DHT content, wet weight, and DNA content of the ventral prostate as that produced in R-3327 G tumor-bearing rats which experienced an antitumor response. These results suggest that SK&F 105657 can produce antitumor effects if a substantial reduction in tissue DHT is achieved. Such reduction in tissue DHT, secondary to inhibition of the tissue 5 alpha-reductase enzyme, appears to be more difficult to achieve in tumors than in the normal prostate. In order to achieve such a DHT reduction in tumor tissue, prostatic cancers with low 5 alpha-reductase activity could be treated with SK&F 105657 on a dose regimen that lowers serum DHT to surgical castration levels, while concomitantly inhibiting the already low tumor tissue 5 alpha-reductase activity. PMID- 1641370 TI - The relationship between cardiovascular complications of estrogen therapy and fibrinolysis in patients with prostatic cancer. AB - To determine the relationship between cardiovascular complications of estrogen therapy and fibrinolysis, fibrinolysis parameters plasminogen, urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1), were assessed in 12 prostatic cancer patients before and 6 weeks after the onset of estrogen therapy. The levels of plasminogen, u-PA, and PAI-1 in the patients treated with the estrogen therapy were significantly higher than those in the patients before the therapy. The t-PA level in the patients during the therapy was significantly lower than that before the treatment. Cardiovascular complications were found in two patients (16.7%) during estrogen therapy. In the two patients, marked elevation of PAI-1 and decreased level of t-PA were observed during the therapy. These results indicate that cardiovascular complications of estrogen therapy in patients with prostatic cancer may be related to hypofibrinolysis resulting from changes of PAI-1 and t PA. PMID- 1641371 TI - The prognostic value of histological grading and mean nuclear volume in human prostatic cancer. AB - Fifty-eight consecutive patients diagnosed with prostatic cancer at transurethral resection in the period 1979-1983 were classified using histological grade according to Shelley, and using an unbiased estimate of mean nuclear volume. We find that both histological grade and mean nuclear volume appear to be significantly associated with survival. In eight of nine patients still alive after 89-130 months mean nuclear volume at diagnosis was in normal range and the histological grade showed a highly differentiated cancer in eight of the nine cases. These findings suggest highly differentiated cancer and normal range of mean nuclear volume may be important for long-term survival. In patients with advanced disease requiring endocrine treatment both histological grading and mean nuclear volume estimates failed to show any prognostic properties with regards to time to progression and time of survival. In patients not subjected to endocrine treatment histologic grade, but not mean nuclear volume, was found to be significantly associated with survival. Subtle changes in disease progression may be diagnosed early by repeated biopsies due to the accuracy and high reproducibility of mean nuclear volume measurements; however, a single estimate of mean nuclear volume has not been shown to offer advantage over histological grade with respect to prognostic properties. PMID- 1641372 TI - [Expression of cytochrome P-450 genes]. AB - Cytochromes P-450 are important in the oxidative metabolism of many endogenous substrates, as well as innumerable drugs, chemical carcinogens, and environmental pollutants. Biochemical analyses of cytochrome P-450 have revealed multiple isoenzymes. Information for synthesis of these isoenzymes is contained in different genes. Based on the degree of relatedness in DNA sequence, the genes for cytochrome P-450 have been classified into different families, constituting cytochrome P-450 multigene superfamily. Particular chemicals induce expression of one or more genes belonging to definite cytochrome P-450 family. Expression of these genes may have served as a mechanism by which the cell respond to specific chemical signals (xenobiotic or hormonal). PMID- 1641373 TI - [Hypoxia and the development of liver damage]. AB - Article presents some aspects of the role of hypoxia in the liver damage. Centrilobular injury, formation of the membranous blebs, release of enzymes are described. This cellular alterations may play an important role in the pathogenesis of the liver diseases. PMID- 1641374 TI - [Metabolism of liver proteins in ethanol poisoning]. AB - The present paper reviews the literature on influence of ethanol and acetaldehyde on synthesis, export and degradation of liver proteins. Direction and intensification changes caused by ethanol and acetaldehyde depend on concentration, time of activity and the way of administration of these compounds, and the way of feeding. PMID- 1641375 TI - [Progress in biology and therapy of aplastic anemia and other conditions of bone marrow failure]. AB - The new aspects in the pathogenesis of aplastic anaemia and others acquired states of bone marrow aplasia as well as congenital defects of the marrow stem cells have been reviewed. Role of immune mechanisms, viruses, chemical and irradiation exposure in the etiology and pathophysiology of bone marrow failure is presented. The new achievements in the treatment of aplastic anaemias including bone marrow transplantation, antilymphocyte globulin, cyclosporin A, high doses of 6-methyl prednisolone and recombinant haemopoietic growth factors are also discussed. PMID- 1641376 TI - [Fever as a homeostatic process accompanying infection]. AB - After a survey of experimental data the author considers the notion that elevated (febrile) temperature acts as an adaptive factor buffering against the disordering of biomembrane homeostasis during infection. Impendance of the membrane homeostasis under infectious conditions occurs due to the certain disturbance of membrane structure caused by pyrogen-induced activation of phospholipases and liberation of arachidonic acid from phospholipid deposits. A consequence of liberation and oxygenation of the arachidonic acid is an outflow of double bonds from the overall pool embedded in the structure of membrane. This in turn leads to an increase of membrane bulk phase transition temperature and to depletion of membrane fluidity at normal (non-febrile) temperature. PMID- 1641377 TI - Toxicological evaluation of aflatoxin and cyclopiazonic acid in broiler chickens. AB - The individual and combined effects of aflatoxin (AF) and cyclopiazonic acid (CPA) were evaluated in day-old Petersen x Hubbard broiler chickens to 3 wk of age. Treatments were arranged in a 2 x 2 factorial with levels of 0 and 3.5 mg AF/kg of feed, and 0 and 50 mg CPA/kg of feed. Production performance, serum biochemistry, and gross pathological observations were evaluated. Body weight gain was significantly (P less than .05) reduced by AF, CPA, and the AF-CPA combination at the end of 3 wk. Aflatoxin significantly increased the relative weight of the kidney and serum concentration of blood urea nitrogen and decreased serum concentrations of protein, albumin, cholesterol, phosphorus, and the activity of lactate dehydrogenase. The toxicity of CPA was expressed through increased relative weights of the liver, kidney, and proventriculus, increased levels of uric acid and cholesterol, and decreased serum phosphorus. The activity of AF-CPA combination was characterized by increased relative weight of the liver, kidney, pancreas, and proventriculus, decreased concentrations of serum albumin and phosphorus, increased concentrations of serum glutamic oxalacetic transaminase and blood urea nitrogen, and decreases in the relative weight of the bursa of Fabricius. Post-mortem examination revealed that the chickens fed CPA and the AF-CPA combination had thickened mucosa and dilated proventricular lumens, hard fibrotic spleen, and atrophy of the gizzard. The data from the present study demonstrate that both AF and CPA alone and the AF-CPA combination can limit broiler performance and adversely affect broiler health. In most cases the effects of AF and CPA were additive. PMID- 1641378 TI - Barley inclusion and avoparcin supplementation in broiler diets. 2. Clinical, pathological, and bacteriological findings in a mild form of necrotic enteritis. AB - The clinical, pathological, and bacteriological findings of a mild form of necrotic enteritis (NE) in broiler chickens are presented. The term subclinical NE (SNE) is proposed for this condition. A diagnosis of SNE was based on the detection of macroscopically visible, focal necrotic lesions in the small intestinal mucosa. The ileal gut contents from SNE birds yielded increased numbers of Clostridium perfringens and reduced numbers of coliform bacteria. Reduced numbers of lactobacilli and streptococci were detected in birds from SNE pens and coccidial oocysts were not found in the rectal contents of SNE birds. Statistical analyses showed strong correlations between SNE and increased feed conversion ratio and retarded growth rate. An increased occurrence of SNE was observed in birds on a diet containing a large amount of barley. PMID- 1641379 TI - Stress measurements on beak-trimmed and untrimmed pullets. AB - Stress in poultry is difficult to define and measure. There is general agreement that some modern poultry production practices may exert a certain amount of stress on birds. Three experiments were conducted to explore possible measures of stress associated with beak trimming and rearing schemes. Experiments 1 and 2 examined different degrees of beak trimming and rearing schemes of wire floor versus litter floor in pullet production. Experiment 3 examined the effect of beak trimming on feed consumption for 14 days after trimming. Adrenal glands of untrimmed birds were heavier (P less than .05) than those of trimmed birds at the end of the pullet growing period in Experiments 1 and 2, evidence that beak trimming reduced overall chronic stress levels. Hearts of untrimmed birds were heavier (P less than .05) than those of trimmed birds in Experiment 1. Hearts and spleens were not affected in Experiment 2. In comparisons of rearing schemes (litter versus wire), birds grown on litter floors had heavier adrenal glands and a greater incidence of cannibalism in the later weeks of Experiments 1 and 2. This indicated that a stressful interaction among penmates had occurred. Birds grown on litter floors consumed more feed than those grown on wire, and the untrimmed birds from both floor types consumed more total feed than trimmed birds. By the end of the growing period, body weights were not different in either study, indicating compensation for any early beak trimming stress. Beak trimming produced a decrease in feed intake in Experiment 3, consumption was reduced (P less than .05) in 5 of the first 8 days after trimming. PMID- 1641380 TI - Dietary zinc methionine effect on eggshell quality of hens drinking saline water. AB - In two experiments individually caged 60-wk-old laying hens were exposed to daily temperatures ranging between 18 and 35 C and given various dietary and drinking water treatments. In Experiment 1 these were: 1) basal diet and town water; 2) basal diet and town water supplemented with 2 g NaCl/L; 3) basal diet supplemented with .2 g zinc methionine (Zinpro-200)/kg diet and town water; or 4) basal diet supplemented with .2 g zinc methionine/kg and town water supplemented with 2 g NaCl/L. In Experiment 2, Treatments 1 and 2 were the same as in Experiment 1. Birds on Treatments 3 and 4 received the town water supplemented with 2 g NaCl/L and the basal diet supplemented with either .5 g zinc methionine/kg (Treatment 3) or .28 g ZnSO4H2O/kg to approximate the same dietary zinc concentration in Treatment 3 (Treatment 4). In both experiments, dietary zinc methionine plus 2 g NaCl/L in the drinking water significantly improved shell breaking strength over those birds on the 2 g NaCl/L with no zinc methionine supplementation. This same pattern occurred for shell weight, shell weight per unit of surface area, and percentage of shell defects. There were no improvements in the parameters measured from the supplementation of ZnSO4. The zinc methionine compound apparently was effective in overcoming the negative influence of the added 2 g NaCl/L of town water. PMID- 1641381 TI - Amino acid fortification of a low-protein corn and soybean meal diet for chicks. AB - Seven experiments were conducted to investigate whether a 19% CP corn and soybean meal (CS) diet could be fortified properly with amino acids (AA) to produce performance in 1- to 3-wk-old chicks equal to that obtained with a 23% CP, CS diet supplemented with Met. In one experiment, the assay was carried out to 6 wk of age. During 4- to 6-wk posthatching, the positive control was a 20% CP, CS diet with added Met and the low-protein diet was a 16% CP, CS diet fortified with limiting AA. The two most limiting AA in the low-protein diet (19% CP) were found to be Met and Lys. Arginine, Val, and Thr were observed to be limiting as well. Weight gain and feed efficiency were substantially increased and body fat content decreased when the low-protein diet was supplemented with the five limiting AA and amino nitrogen in the form of Glu. Addition of potassium had no effect on performance of chicks fed the AA-fortified, low-protein diet. With all trials considered together, chicks fed the low-protein diet fortified with the five limiting AA and Glu gained at the same rate with similar feed efficiency and had estimated body fat levels comparable to birds fed the 23% CP, positive control diet. From 3 to 6 wk of age, chicks fed the AA-fortified, 16% CP diet had growth performance similar to chicks fed the 20% CP, positive control diet. PMID- 1641382 TI - Effects of dietary aluminum and niacin on chick tibiae. AB - Effects of dietary aluminum chloride and niacin on bone mineral content and bone structural measurements were studied using young male Leghorn chicks. Standard chick rations containing .8% Ca and .4 or .5% available P were fed as control diets in three experiments. Experimental diets contained .05, .1, or .3% Al, or 1.0 or 1.5% niacin, or both and were fed for 2 wk. Tibia weights were decreased by 1.5% niacin, .3% Al, and by .1% Al plus 1.5% niacin (P less than .05). Breaking strength of tibiae was decreased (P less than .05) by 1.5% niacin, .1% Al, and .1% Al plus 1.5% niacin. Ultimate stress, which is force per unit area, was decreased by .3% Al and .05% Al plus 1.5% niacin (P less than .05). Niacin had no significant effect on bone mineral content. In Experiment 3, .3% Al decreased P, Ca, Mg, and Zn content of the tibiae (P less than .05). These findings indicate that feeding high levels of supplemental niacin results in decreased bone strength in chicks with no change in mineral content of the tibiae. Aluminum fed at levels of .3% of the diet causes a decrease in bone strength with concomitant changes in bone mineral content. PMID- 1641383 TI - The effects of dietary protein level on the reproductive performance of bobwhite hens. AB - Two experiments were conducted to evaluate the protein requirement of adult bobwhite quail. Flight-type quail were used in one experiment and meat-type quail in the other. Corn and soybean meal diets containing 12, 15, 18, 21, and 24% protein were fed. Increasing the protein level of the diet from 12 to 15% significantly increased egg production with the flight-type bird. However, only a nonsignificant increase in egg production was obtained with the meat-type birds when the protein level was increased to 15%. Higher levels of protein did not result in further increases in egg production in either strain. Increasing the protein from 12 to 18% (flight) or 21% (meat) resulted in increased egg weight. Egg mass of flight-type hens receiving 18 and 21% protein was significantly greater than egg mass from hens receiving 12 and 15% protein. Hatch of fertile eggs, hatch of total eggs, chick weight, or weight of adult birds were not affected by protein level. Feeding the 12% protein diet resulted in significantly reduced fertility in the flight-type birds but not in the meat-type birds. PMID- 1641384 TI - Progeny performance when dams and chicks are fed supplemental zinc. AB - Three consecutive trials involving approximately 700 to 800 broilers (0 to 28 days) were conducted to examine effects on growth and immunity of chicks after supplementing dams with inorganic Zn versus organic Zn. Offspring from hens fed a basal diet (72 mg Zn/kg) or diets with 152 mg Zn/kg supplemented with ZnO or organic Zn-Met were randomized across four battery brooders. Chicks were fed a starter diet without supplemental Zn containing 100 mg Zn/kg or diets supplemented with 40 mg/kg Zn from ZnO and DL-Met or Zn-Met containing 140 mg Zn/kg. No differences among treatments (P greater than .05) were found in feed conversion or average BW. Supplemental Zn-Met in hen diet increased (P less than .06) cellular immune response in progeny. Embryonic bone weights were higher (P less than .05) in progeny when dams were fed Zn-Met. Zinc as Zn-Met in diets of dams and progeny enhanced primary antibody titers to Salmonella pullorum antigen. PMID- 1641385 TI - Effects of dietary amino acid level and duration of finisher period on performance and carcass content of broilers forty-nine days of age. AB - Two studies were conducted to evaluate feeding reduced levels of amino acids (AA) to broilers during the finisher period. Birds grown to 42 days on nutritionally complete diets were fed diets formulated to contain a minimum of 70, 80, 90, 100, or 110% of recommended AA levels for periods of 3, 5, or 7 days prior to slaughter at 49 days of age. Body weight, feed intake, feed utilization, dressing percentage, and abdominal fat content were determined. For finisher periods of 3 to 5 days, a reduction in recommended dietary AA levels may be utilized without impairment of body weight gains of broilers. Extending the finisher period to 7 days resulted in significant (P less than .05) reduction of body weight gains on diets with AA levels less than 90% of recommended levels. Feed utilization was more sensitive to reduction in AA levels and may be affected adversely even by a 5-day withdrawal period. Dressing percentage was reduced in some instances, and abdominal fat generally increased when reduced AA levels were fed. The economics of feeding reduced AA levels must be considered in evaluating the results of the present studies. PMID- 1641386 TI - Effect of progesterone in vitro on luteinizing hormone production in hen pituitary cells pretreated with estrogen. AB - Isolated cells from the pituitary gland of nonlaying hens were preincubated in vitro with or without estradiol-17 beta (E2), and then incubated with or without progesterone (P4), and luteinizing hormone (LH) in the cells and media was measured by a homologous radioimmunoassay. When the cells were preincubated with E2 for 2 h and then incubated with P4 for 4 h, cellular LH was increased, but LH in the medium remained unchanged. The increase in cellular LH in response to P4 was dose-dependent. Protein synthesis inhibitors (cycloheximide, actinomycin-D, and alpha-amanitin) blocked the response of the cells to P4. The results suggest that LH production in estrogen-primed pituitary cells of the hen was stimulated by P4 through a protein-synthesizing pathway. PMID- 1641387 TI - Ultrastructure of the rat pancreas after experimental duct ligation. II. Duct and stromal cell proliferation, differentiation, and deletion. AB - Ligation of the pancreas in rats was followed by rapid atrophy of the distal part of the gland, where deletion of the acinar cells by apoptosis and simultaneous extensive proliferation of duct cells resulted in the lobules being converted into groups of closely packed small ducts within 5 days. We found no ultrastructural evidence that cells lining these small ducts arose from acinar cells by a process of dedifferentiation, as has been suggested by some investigators. During the succeeding weeks, some of the ductal lining cells developed islet cell or partial acinar cell differentiation. The latter soon died by apoptosis, and some ductlike and islet cells were also deleted by this means. Most of the apoptotic bodies formed in the ducts were phagocytosed by intraepithelial macrophages. In the longer term, continuing apoptosis eventually resulted in the disappearance of many ducts, only their thickened basal laminae remaining. Differentiation of stromal fibroblasts into contractile myofibroblasts may have contributed to shrinkage of the duct-obstructed glandular tissue, and apoptosis of endothelial cells probably accounted for the associated reduction of the capillary bed. PMID- 1641388 TI - The intestinal peptide PEC-60 inhibits insulin secretion in the mouse and the rat. AB - The newly discovered 60-amino-acid porcine intestinal peptide, PEC-60, shows a structural similarity to pancreatic secretory trypsin inhibitor. PEC-60 was recently demonstrated to inhibit glucose-stimulated insulin secretion from the perfused rat pancreas. We examined in this study whether the peptide affects basal and stimulated insulin secretion in vivo. Purified porcine PEC-60 was injected intravenously in mice at 1 or 8 nmol/kg alone or together with glucose (2.8 mmol/kg) or the cholinergic agonist carbachol (0.16 mumol/kg). PEC-60 was found to inhibit glucose- and carbachol-induced insulin secretion (p less than 0.01 and p less than 0.05, respectively) at 8 nmol/kg, whereas at 1 nmol/kg, the peptide had no effect. In contrast, basal plasma insulin levels were not affected by PEC-60. In a second experimental series, PEC-60 was infused intravenously in rats at 17 or 68 pmol/min alone or together with glucose (56 mumol/min). At 68 pmol/min (p less than 0.01), but not at 17 pmol/min, PEC-60 inhibited glucose stimulated insulin secretion. The peptide had no influence on basal plasma insulin levels. It is concluded that the newly isolated intestinal peptide, PEC 60, inhibits stimulated insulin secretion under in vivo conditions both in the mouse and in the rat without affecting basal insulin secretion. PMID- 1641389 TI - Mitotic activity and DNA synthesis of rat islet cells following partial pancreatectomy. AB - The regenerative potential of the adult rat pancreas following a 50% pancreatectomy was investigated. Blood glucose values and body weight were unchanged by the procedure. The mitotic index (MI) of alpha, beta, and exocrine cells was examined in formalin-fixed sections of the pancreas stained for hormones and 5-bromo-2'-deoxyuridine (BrDU) after treating the animals with 2.5 mg/kg colchicine and/or 50 mg/kg BrDU prior to sacrifice. The MI was unchanged within the control group. For pancreatectomized versus control animals, in beta cells after 5 days the MI was 0.84% versus 0.41% (p less than 0.05), while 7 days postoperatively it was 1.04% versus 0.57% (p less than 0.01); in alpha cells, the MI was 0.32% versus 0.17% (p less than 0.05) at 5 days and 0.47% versus 0.24% (p less than 0.05) at 7 days. The MI of exocrine cells rose transiently on day 3 postoperatively to 0.74% in the pancreatectomized group but remained low at 0.15% (p less than 0.01) in the control group. The mean ratio of BrDU + ve beta cells was 1.19% in the pancreatectomy group and 0.45% in the control group on day 5 postoperatively (p = 0.01). A highly significant (r = 0.97; p less than 0.001) correlation existed between BrDU + ve and mitotic cells. There was no difference between the two groups in the area occupied by insulin-positive cells in pancreatic sections, nor in the number of beta cells per islet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641390 TI - Inhibitory effect of islet amyloid polypeptide of glucose-induced proinsulin biosynthesis in rat insulinoma cells. AB - Islet amyloid polypeptide (IAPP) has been recently identified as the principal constituent of amyloid deposits in pancreatic islets of patients with type 2 (non insulin-dependent) diabetes mellitus and causes insulin resistance in some target cells. In addition, glucose-induced insulin secretion is inhibited by IAPP. We studied the effect of IAPP on proinsulin biosynthesis in rat insulinoma (RINr) cells. Glucose at concentrations of 0, 15, 30, 60, 100, and 300 mg/dl stimulated proinsulin biosynthesis in a dose-responsive and and actino-mycin D-inhibitable manner after 6 h of incubation. At a glucose concentration of 300 mg/dl, IAPP decreased the mean responses of proinsulin biosynthesis to 61.2 and 29% at concentrations of 0.1 and 1 microM, respectively, compared with the IAPP-free control. In conclusion, IAPP inhibits glucose-induced proinsulin biosynthesis in RINr cells. IAPP might play an important role in the pathogenesis of type 2 diabetes mellitus. PMID- 1641391 TI - Effects of antioxidants and free radical scavengers in three different models of acute pancreatitis. AB - The present studies were done to evaluate the therapeutic potential of several antioxidants and free radical scavengers in three different models of acute pancreatitis. (a) Edematous pancreatitis with acinar cells necrosis was induced by seven hourly intraperitoneal injections of 50 micrograms of caerulein per kg in mice. (b) Hemorrhagic pancreatitis was induced by feeding a choline-deficient, ethionine-supplemented (CDE) diet in mice. (c) Hemorrhagic pancreatitis was induced by retrograde infusion of 0.6 ml of 5% sodium taurocholate into the pancreatic duct in rats. The following antioxidants and free radical scavengers were given at various doses intravenously, subcutaneously, or intraperitoneally before the onset of pancreatitis: Ebselen [2-phenyl-1,2-benzisoselenazol-3(2H) one], superoxide dismutase, catalase, deferoxamine (Desferal), dimethyl sulfoxide, or allopurinol. The severity of pancreatitis was assessed at various times after its onset by determination of serum amylase and pancreatic weight (edema), by grading of histological alterations, and by determination of survival (survival determined in models of hemorrhagic pancreatitis). In general, free radical scavengers and antioxidants ameliorated edema and inflammation to a greater degree than necrosis and the increase in serum amylase. Superoxide dismutase (as did Ebselen in previous studies) exerted beneficial effects on survival in diet-induced pancreatitis in the absence of marked effects on pancreatic necrosis, suggesting that these beneficial effects are due to amelioration of extrapancreatic complications that often contribute to mortality in acute pancreatitis. None of the antioxidants had major beneficial effects in taurocholate-induced hemorrhagic pancreatitis. Thus, formation of free radicals may be important for progression and outcome in diet-induced and, to a lesser degree, in caerulein-induced pancreatitis but not at all in taurocholate-induced pancreatitis. Different models of pancreatitis may, therefore, involve different degrees and mechanisms of free radical formation. Despite the amelioration of edema and the beneficial effects on mortality seen for some antioxidants in some of the models, antioxidants and free radical scavengers appear to have only a limited potential for treatment of acute pancreatitis. PMID- 1641392 TI - Clinical utility of the serum CA 19-9 test for diagnosing pancreatic carcinoma in symptomatic patients: a prospective study. AB - The diagnostic accuracy of the serum CA 19-9 determination was prospectively evaluated in patients selected for the presence of signs or symptoms highly suggestive for pancreatic cancer. Of 110 patients included in the study, 54 had a final diagnosis of pancreatic adenocarcinoma (49% prevalence). CA 19-9 values were higher than 40 U/ml in 45 patients with pancreatic carcinoma and in 18 of the 56 patients with other final diagnosis (sensitivity, 0.83; specificity, 0.68; positive predictive value [PPV], 0.71; negative predictive value [NPV], 0.81). The serum CA 19-9 determination was not capable of shortening the diagnostic workup of patients with strong clinical suspicion of pancreatic cancer since adequate imaging of the pancreas was required to confirm or exclude the diagnosis. However, values above 120 U/ml were strongly suggestive for pancreatic carcinoma in the overall population (PPV, 0.85) and they were diagnostic (PPV, 1.0) in the anicteric portion. Combined with pancreatic imaging, the CA 19-9 was an excellent confirmatory test; a normal value in a patient with negative imaging ruled out pancreatic carcinoma as the cause of symptoms (NPV, 1.0), whereas a pathological result in the presence of positive or equivocal pancreatic radiology was highly suggestive for the presence of the disease (PPV, 0.93). PMID- 1641393 TI - Horseshoe anomaly of the pancreas. AB - A 72-year-old man with recurrent pancreatitis and a horseshoe-shaped anomaly of the pancreas is described. The diagnosis was made by endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography scan; laparotomy was confirmatory. The abnormal duct branched to the lower left from an enlarged Santorini's duct; a thin Wirsung's duct was joined at its distal portion to the junction of the abnormal duct. The anomaly was associated with a cystic dilatation of the common bile duct with stone and cholecystolithiasis. This anomaly is considered to be a variation of the dominant dorsal duct syndrome. PMID- 1641394 TI - Detection of intrahepatic human islets following combined liver-islet allotransplantation. AB - This article describes the localization of intact insulin-containing intrahepatic islets after combined liver-islet allotransplantation. The patient was a 36-year old woman who underwent upper abdominal exenteration for neuroendocrine carcinoma; 289,000 islets were transplanted via portal vein infusion immediately after complete revascularization of the liver. Immunosuppression was with low dose FK-506. OKT3 and steroids were used to treat one rejection episode 2 weeks after transplantation, but the patient subsequently developed multiple infections and died 109 days after transplantation. At autopsy, the transplanted liver did not show any sign of rejection and well-preserved islets were present in portal triads sampled from the anterior inferior edge of the right lobe. Immunohistochemical labeling confirmed the presence of insulin-containing cells. This finding indicated that human islets can survive after intrahepatic allotransplantation, despite positive cross-match with no HLA antigen match, suggesting that upper abdominal exenteration and liver transplantation may constitute a protective factor for the survival of allogeneic human islets. PMID- 1641395 TI - The fatty acid chain elongation system of mammalian endoplasmic reticulum. AB - Much has been learned about FACES of the endoplasmic reticulum since its discovery in the early 1960s. FACES consists of four component reactions, requires the fatty acid to be activated in the form of a CoA derivative, utilizes reducing equivalents in the form of NADH or NADPH, is induced by a fat-free diet, resides on the cytoplasmic surface of the endoplasmic reticulum, appears to function in concert with the desaturase system and appears to exist in multiple forms (either multiple condensing enzymes connected to a single pathway or multiple pathways). FACES has been found in all tissues investigated, namely, liver, brain, kidney, lung, adrenals, retina, testis, small intestine, blood cells (lymphocytes and neutrophils) and fibroblasts, with one exception--the heart has no measurable activity. Yet, much more needs to be learned. The critical, inducible and rate-limiting condensing enzyme has resisted solubilization and purification; the purification of the other components has met with limited success. We know nothing about the site of synthesis of each component of FACES. How is each component enzyme integrated into the endoplasmic reticulum membrane? Is there a single mRNA directing synthesis of all four components or are there four separate mRNAs? How are elongation and desaturation coordinated? What is (are) the physiological regulator(s) of FACES--ADP, AMP, IP3, G-proteins, phosphorylation, CoA, Ca2+, cAMP, none of these? The molecular biology of FACES is only in the fetal stage of development. We are only scratching the surface--it is an undiscovered country. PMID- 1641396 TI - Inositol-containing lipids in higher plants. PMID- 1641397 TI - The role of transacylases in the metabolism of arachidonate and platelet activating factor. PMID- 1641398 TI - Chemistry and biochemistry of taurolipids. PMID- 1641399 TI - Idiosyncratic reactions to antidepressants: a review of the possible mechanisms and predisposing factors. AB - Antidepressants, a widely used group of drugs, are associated with a range of idiosyncratic reactions affecting in particular the liver, skin and both the hematological and central nervous systems. These reactions seem to be mediated by chemically reactive metabolites formed by the cytochrome P450 enzyme system, the toxicity occurring either directly or indirectly via an immune mechanism. Individual susceptibility is determined by factors, both genetic and environmental, which result in inadequate detoxication of the chemically reactive metabolite. Prevention of such reactions will depend on either the development of new compounds which are not converted to toxic metabolites or by prediction of individual susceptibility prior to drug administration. PMID- 1641400 TI - Carcinogen-mediated oxidant formation and oxidative DNA damage. AB - This article reviews the experimental data that points to formation of reactive oxygen species (ROS) and oxidative DNA base damage as being important contributors to cancer development. Particular emphasis is placed on the role they play in genetic changes occurring during tumor promotion. A number of structurally different anticarcinogenic agents inhibit ROS production and oxidative DNA damage as they inhibit inflammation and tumor promotion. This underlines the importance of ROS and oxidative genetic damage to the carcinogenic process. It also points to the possibility that some types of cancer may be preventable if the cycles of tumor promotion can be interrupted. PMID- 1641401 TI - Metal carcinogenesis: mechanistic implications. AB - Cancer epidemiology has identified several metal compounds as human carcinogens. Recent evidence suggests that carcinogenic metals induce genotoxicity in a multiplicity of ways, either alone or by enhancing the effects of other agents. This review summarizes current information on the genotoxicity of arsenic, chromium, nickel, beryllium and cadmium compounds and their possible roles in carcinogenesis. Each of these metals is distinct in its primary modes of action; yet there are several mechanisms induced by more than one metal, including: the induction of cellular immunity and oxidative stress, the inhibition of DNA metabolism and repair and the formation of DNA- and/or protein-crosslinks. PMID- 1641402 TI - Antihypertensive drugs: individualized analysis and clinical relevance of kinetic dynamic relationships. AB - Individualized approaches to antihypertensive therapy are being widely advocated. Ideally these should incorporate rational prospective methods for drug and dosage selection but progress has been hampered by the paucity of information about dose (and plasma concentration-) response relationships. However, in several recent clinical studies, concentration-effect analysis has been used to characterize kinetic-dynamic relationships in individual patients for a range of antihypertensive drugs. This approach provides an integrated mathematical description of drug response which has potential utility for quickly identifying poor or nonresponders and for determining individual dose requirements for optimum longterm blood pressure control. PMID- 1641403 TI - Fibrogenesis in cirrhosis. Potential for therapeutic intervention. AB - Liver cirrhosis is an end stage of several diseases that affect the liver chronically. It is characterized, among other things, by excess collagen deposition, distortion of liver architecture, tissue malfunction and hemodynamic alterations. Many of the complications of cirrhosis may result from excess matrix deposition. Therefore, prevention of collagen accumulation or removal of collagen deposits could ameliorate the disease. In this article we discuss the pathophysiology of liver fibrosis and we describe various compounds with antiinflammatory and antifibrogenic activity. We discuss their possible mechanism of action and we describe animal and clinical studies in which these compounds have been utilized. PMID- 1641404 TI - Pathophysiology and pharmacotherapy of cholelithiasis. AB - Several factors are involved in the development of gallstone formation: formation of supersaturated bile; nucleation; formation, retention and adhesion of cholesterol crystals and eventually stone growth. The dynamics of the gallbladder may play a key role in the overall process. The pathophysiologic theory of cholesterol gallstone formation and the knowledge of their physico-chemical properties support the modern concept of gallstone therapy. Chenodeoxycholic and ursodeoxycholic have been widely used as cholesterol gallstone dissolving agents and evaluated in terms of efficacy and safety. PMID- 1641405 TI - The clinical pharmacology of angiotensin converting enzyme inhibitors in chronic heart failure. AB - ACE inhibitors (ACEIs) have now been shown to improve symptoms and survival in patients with mild, moderate and severe chronic heart failure. Their mechanism of action is thought to be a combination of RAAS suppression and augmentation of bradykinin and prostaglandins. Although ACE inhibitors improve hemodynamics post myocardial infarction, we do not yet have consistent data on their effects on symptoms or survival in these particular patients. One other potential benefit is their effects on reperfusion injury and free radicals. As yet only minor differences have been found to exist between different ACEIs but increasing attention is now being focussed in this direction. PMID- 1641406 TI - Venomous mammals. AB - It is not widely appreciated that mammals can be venomous in the manner of snakes and lizards. However, it was first demonstrated scientifically 50 years ago in the case of the American short-tailed shrew. Subsequently, similar evidence has been obtained from European shrews and the Haitian solenodon, but research in this area has been almost completely neglected for the last 20 years. In complete contrast to what has been learned about other animal venoms, the identity and mode of action of mammal venom toxins are still unknown. This review draws attention once more to the pioneering work undertaken in the 1940s and 1950s, exploring in more detail than hitherto why the implications of mammal venom are just as important as the chemistry and pharmacology of the phenomenon itself. PMID- 1641407 TI - The use of pharmacogenetic techniques in drug abuse research. AB - Pharmacogenetics, the study of genetic factors underlying individual differences in response to drugs, has proven useful for demonstrating that there are large genetic differences in response to a number of abused drugs. Pharmacogenetics also provides a number of useful tools for studying mechanisms underlying the effects of drugs. This review discusses pharmacogenetic techniques with potential utility for drug abuse research and provides examples of their use in studies of the effects of acute and chronic nicotine, cocaine and opiate administration. The importance of using genetically standardized animal models in behavioral and pharmacological research is also discussed. PMID- 1641408 TI - Adhesive interactions in angiogenesis and metastasis. AB - A variety of adhesive interactions must take place between the tumor cell and the host vasculature in order to potentiate both tumor expansion and metastatic tumor spread. The study of tumor cell and blood vessel adhesive interactions becomes essential for our understanding of the malignant process, especially with regard to organ-specific tumor metastasis. In this article we will review recent progress made in our understanding of the nature of (i) receptor mediated adhesion of endothelial cells to extracellular matrix components and (ii) adhesion of tumor cells to endothelial adhesion molecules and to components of the subendothelial basement membrane. PMID- 1641409 TI - Xenobiotic metabolism by prostaglandin H synthase. AB - During the metabolism of arachidonic acid by prostaglandin H synthase many chemicals including carcinogens are metabolized. These chemicals are metabolized by either the peroxidase activity of prostaglandin H synthase, the peroxyl radicals generated during arachidonic acid oxygenation, or a combination of these two mechanisms. In many cases, the chemical metabolism results in the formation of reactive metabolites that have mutagenic activity and potential carcinogenic activity. In other cases, the chemicals are detoxified. Chemical metabolism that occurs during arachidonic acid oxygenation may be an important determinate of chemical toxicity in extra-hepatic tissues. PMID- 1641410 TI - Sympathetic nervous system and behavioral responses to stress following exercise training. AB - This study tests the hypothesis that a short-term (16 weeks) exercise program modifies sympathetic nervous system (SNS) and selected behavioral responses to acute psychological stress. Twenty-four previously sedentary middle-aged men with maximal aerobic capacity (VmaxO2) values less than 40 ml.kg-1.min-1 were assigned to experimental (n = 12) and control (n = 12) groups. All subjects performed a modified Stroop test (18 min) at pre- and postexercise training during which intravenous blood samples were drawn at three time intervals for plasma catecholamine (CA) determination. Motor performance was continuously recorded for assessment of premotor (PMT) and motor (MOT) components of reactions time. A set of anagrams were administered immediately following the modified Stroop to determine the level of cognitive fatigue induced. At both pre- and postexercise intervention, the total group (n = 24) manifested significant (p less than or equal to 0.05) elevations in state anxiety, heart rate, and plasma norepinephrine. No significant changes occurred over time on PMT or MOT. There were significantly (p less than or equal to 0.01) lengthened anagram performance scores poststress compared to nonstress values. The experimental group exercise trained 3 days/week for 16 weeks, resulting in a 20% increase in VO2max. However, there were no group differences on the CA or behavioral responses to the modified Stroop at pre- or postintervention. These findings do not support the hypothesis that short-term aerobic training significantly alters SNS activity or behavioral measures of central processing in middle-aged men exposed to an acute psychological challenge. PMID- 1641411 TI - Intraventricular neuropeptide Y injections stimulate food intake in lean, but not obese Zucker rats. AB - We examined the effect of acute third intraventricular (IVT) injections of either saline or NPY (0.95, 3.0, 9.5, or 30.0 micrograms in 1 microliter) on the 1-, 4-, and 22-hour postinjection food and water intake of female obese (fa/fa), heterozygous lean (Fa/fa), and homozygous lean (Fa/Fa) Zucker rats. None of the doses of NPY had an effect on either food or water intake of fa/fa rats. A significant increase of food intake was seen in Fa/Fa rats at 1 and 4 hours after the 3.0 micrograms injection of NPY and at 1, 4, and 22 hours after the 9.5 micrograms injection of NPY. Both 3.0 and 9.5 micrograms of NPY also stimulated 1 and 4-hour postinjection food intake of Fa/fa rats, although this effect was significant only at 4 hours after the 3.0 micrograms dose. NPY had a less reliable effect on water intake; 3.0 micrograms of NPY stimulated 1-hour postinjection water intake of Fa/fa rats and 4-hour postinjection water intake of Fa/Fa rats. These results indicate that lean, but not obese Zucker rats, respond by eating more to centrally administered NPY. This deficit is similar to the effects seen with IVT insulin injections and may be a result of a common receptor mediated mechanism. PMID- 1641412 TI - Emotivity, personality, and task-dependent EEG asymmetry. AB - In order to verify if task-dependent EEG asymmetry is related to emotivity or personality traits, the relationship between EEGraphic (EEG mapping) asymmetry, personality aspects, and emotional-affective state in 12 healthy volunteers was evaluated by means of standardized methods (SAD and CPI). Our subjects show an EEG asymmetry which is currently attributed in the literature to anxiety. In our subject the absence of anxiety and the presence of hyperthymic characteristics suggests that the different individual trends observed in various studies which have used methods similar to ours, could, at least partly, depend on interference on these variables. PMID- 1641413 TI - Diazepam facilitates acceptance of alien lambs by postparturient ewes. AB - The aim of this study was to determine the effect of diazepam on the behavior of parturient ewes towards alien lambs. There is evidence that benzodiazepines cause behavioral changes during the lactation period in rats. In two independent experiments, it was found that the ewes acceptance of alien lambs significantly increased following a single injection of the benzodiazepine, diazepam, given either 1 or 12 h after parturition. In a third experiment, in which the alien lamb was not permitted to suckle during a period of 2 h after the injection, the diazepam treatment did not provoke significant differences in maternal behavior of the ewes, although in the ewes treated with diazepam, suckling clearly tended to increase. At the dose employed (20 mg), administered 1 h after birth, diazepam caused no signs of sedation as assessed in an open-field test carried out 3 h after parturition. This doesn't eliminate the possibility of diazepam having a sedative effect in the period of 2 h immediately after its administration and before the test and, in this way, facilitating suckling which could be responsible for the maternal behavior observed after this period. As diazepam gives rise to an enhanced GABAergic activity in the brain, these observations suggest that a GABAergic mechanism could also play a role in the process whereby ewes form a selective bond with their own offspring. PMID- 1641414 TI - Changes in limbic neuronal function during hormonal induction of lordosis in behaving hamsters. AB - Several limbic structures influence copulatory behavior and contain receptors for estradiol and progesterone. In the present study, single neuron activity was recorded from septal, amygdaloid, and other limbic regions during the hormonal induction of lordosis in behaving golden hamsters. Limbic neurons had low firing rates and a small number showed firing associated with orienting, sniffing, and rearing. Progesterone administration to estradiol-primed hamsters produced the following neuronal effects: a reduction in the number of active neurons and narrowing of dynamic activity range; enhanced neuronal responsiveness to face stimulation; and lordosis-correlated firing, consisting of depressed activity during lordosis and increased firing at response onset or offset. Unlike previously studied midbrain and hypothalamic neurons, control progesterone injections that didn't produce lordosis were about as effective in altering limbic neuronal activity levels and sensory responsiveness as behaviorally effective injections. The progesterone effects on limbic neurons are consistent with previous evidence suggesting that these neurons tend to suppress lordosis. The significance of these results to hormone influences on epilepsy is discussed. PMID- 1641415 TI - Reaching behavior in the rat: absence of forelimb peripheral input. AB - In order to test whether peripheral input from a moving forelimb is essential for reaching in rats, the effects of dorsal rhizotomy C5-Th2 were examined. Rats were trained to reach for a food pellet in the horizontal tube or on a tray. Reaching attempts before and after bilateral forelimb deafferentation were monitored by continual recording using magnetic induction. Deafferented animals were able to initiate and generate the motor program of reaching, but modulation of its ongoing execution was lost. Peripheral input from moving forelimb was necessary for the effective performance of grasping; the duration of the manipulative part of reaching was significantly prolonged and the success of grasping was markedly decreased. Also, the aiming of forelimb was impaired, probably by disturbing of body forelimb postural coordination. No significant changes were found in the execution of forelimb protraction. It is concluded that somesthetic feedback is not required for execution of forelimb protraction, but it is necessary for grasping. PMID- 1641416 TI - Effects of various stressors on milk release in the rat. AB - This study investigated the effect of four stimuli on milk release (MR), namely, sound, nociception, novelty, and restraint. The role of the ensuing adrenocortical response in the suppression of MR was also evaluated. Plasma corticosterone (CORT) levels were measured at 0 (basal), 15, 30, and 60 min during the suckling sessions to determine whether elevated CORT normally associated with stress could be inhibitory to MR. Compared to nonstressed lactators, dams exposed to sound demonstrated no suppression in MR, but a significant increase in plasma CORT. Pain did not alter milk yield and elevated CORT only at the end of the first hour of exposure. During novelty, MR was suppressed and again CORT was only elevated at the end of the sampling period. Restraint decreased milk yield and increased CORT. During novelty, MR appeared to be regulated by an adrenal factor, which remains to be identified. The peripheral opiates seem to be partially involved during restraint. In conclusion, not all types of aversive stimuli interfere with MR. Of those which do, different mechanisms seem to be implicated depending upon the nature of the stressor. Furthermore, reduced MR during stress is not a direct consequence of increased CORT. PMID- 1641417 TI - Regulation of peripheral glucagon concentrations in cyclic, pregnant, and lactating rats. AB - In the rat, peripheral glucagon concentrations were studied throughout pregnancy and lactation. Basal glucose concentrations were decreased during late pregnancy and during lactation, but basal glucagon concentrations were not affected. Infusion of glucose (7.4 mg/min) caused an elevation of the glucose concentrations, which became lower in the course of lactation, and a suppression of the glucagon concentrations which was the same throughout pregnancy and lactation. Ingestion of 336 mg of glucose or 1 g of rat chow throughout pregnancy and lactation induced a transient increase of the glucose concentrations and a biphasic glucagon response: following a short-lasting elevation, the glucagon concentrations became suppressed. The glucagon responses to these tests did not change during pregnancy and lactation. It is concluded that the regulation of the peripheral glucagon concentration is not affected by pregnancy or lactation, and that the response of the glucagon concentration to a metabolic challenge varies with the kind of test (oral or intravenous) used. PMID- 1641418 TI - Neural androgen receptors and scent marking of male gerbils: modulation by females. AB - The involvement of brain cytosolic androgen receptors in the female-induced increase in scent-marking behavior of male Mongolian gerbils was studied. Scent marking activities and serum testosterone concentrations were measured in low marking control males and in males with increased scent-marking activities, stimulated by the presence of conspecific females in the same room. For every individual male the concentrations and affinities of androgen receptors were determined in four parts of the brain, which contained the hippocampus, septum, corpus striatum, amygdala, stria terminalis, and the hypothalamus. Compared to the basal unstimulated period, the marking activities of male gerbils significantly increased 58% during the presence of female conspecifics in their housing room. The serum testosterone concentrations did not change significantly during female presence. The association constants of the cytosolic androgen receptors were higher in the female-stimulated males compared to isolated control males. In contrast, the cytosolic receptor concentration was reduced. The difference reached significance in one of the brain parts. Individual levels in scent-marking activities could not be explained by correlation with individual androgen receptor parameters. The present results suggest that increased androgen binding in the brain may be involved in the elevation of scent-marking activities in male gerbils, caused by urinary chemical signals of female conspecifics. PMID- 1641419 TI - Effects of steroids on the olfactory function of the dog. AB - Twenty-four (24) mature, mixed breed, healthy dogs weighing from 14.6 kg to 27.6 kg were used to study the effects of various steroids on the olfactory function of the dog using olfactory detection threshold as an index. Two odorants were used, viz; benzaldehyde and eugenol. Of the various steroids used, only dexamethasone produced classical signs of Cushing's syndrome in the dogs. However, all dogs that received either dexamethasone alone or hydrocortisone plus DOCA exhibited a significant elevation in the olfactory detection threshold for both odorants without any observable structural alteration of the olfactory tissue using light microscopy. On the other hand, neither DOCA, hydrocortisone alone, nor any of the vehicles used in the study significantly altered the olfactory function of the dogs. The results show that Cushing's syndrome can be experimentally produced in dogs using exogenous steroids and that this condition diminishes the olfactory capability of the dog without producing classical signs of the disease. PMID- 1641420 TI - Photoperiod modulates the effects of steroids on sociosexual behaviors of hamsters. AB - Female hamsters (Mesocricetus auratus) exposed to a short photoperiod for 8 weeks were ovariectomized, as were hamsters that were maintained in a long photoperiod. We then tested the effect of photoperiod on the ability of progesterone (P) to reduce aggression, as well as on the effects of estrogen (E), alone and with P, on the display of lordosis. Before hormone treatments, photoperiod did not affect the display of aggressive behaviors. When treated with steroids, short-day females were more aggressive than long-day housed animals, especially when tested using male intruders. Also, exposure to short days reduced the activational effects of E and E+P upon lordosis behavior. These findings confirm that photoperiod can modulate the behavioral effects of E and E+P in female hamsters. Furthermore, the results indicate that behavioral effects of P which do not depend upon E priming are also influenced by photoperiod. PMID- 1641421 TI - Effects of early postnatal malnutrition and chlordiazepoxide on experimental aversive situations. AB - In order to study the lasting consequences of brain changes caused by early malnutrition, rats were fed a protein-deficient diet from birth until 49 days of age and a balanced diet from day 50 to day 70. At 49 and 70 days of age, independent groups of animals were tested in the locomotor activity, step-down inhibitory avoidance, and flinch-jump nociceptive tests. Also, at 49 days of age, malnourished and control rats were sacrificed in order to evaluate the weight of brain regions. Malnourished rats had lower body and brain weights (telencephalon and brain stem) than control rats. Malnourished rats also showed less locomotor activity at the beginning of the test session, lower flinch and jump thresholds, and longer step-down latencies than control animals. Chlordiazepoxide (5 mg/kg, IP) shortened step-down latency of well-nourished rats, but was ineffective in malnourished rats. These and previously reported results indicate that early protein malnutrition causes long-lasting impairment of neuronal systems underlying emotional behavior. PMID- 1641422 TI - Paraventricular hypothalamic obesity in rats: role of corticosterone. AB - The role of adrenal glucocorticoid hormones in the weight gain produced by lesions of the paraventricular nuclei was explored in two experiments. In the first experiment, female rats with PVN lesions were found to have normal a.m. plasma corticosterone concentrations and blunted, albeit still elevated, p.m. concentrations. Nighttime corticosterone levels were moderately correlated with plasma insulin levels. In the second experiment, adrenalectomy markedly suppressed weight gain in animals with very large PVN lesions (mean weight gain of 33.0 g/20 days compared to 137.6 g/20 days for PVN rats with sham adrenalectomies). In the ADX-PVN group, there was a +0.90 correlation between plasma corticosterone levels and weight gain. Administration of corticosterone restored the abnormal weight gain in ADX-PVN animals. It is concluded that the steroid receptors mediating this effect of corticosterone lie outside the hypothalamus. PMID- 1641423 TI - Photostimulation of blackheaded bunting: subjective interpretation of day and night depends upon both photophase contrast and light intensity. AB - Blackheaded buntings were exposed to constant dim light (approximately 2 lux) for 77 days and subsequently to 12:12 illumination, consisting of either dim light:complete darkness (dl:dk) (2:0 lux) or bright light:dim light (bl:dl) (10, 35, and 90 lux:2, 10, and 35 lux, respectively, with 180 degrees bl:dl transitions) for 2-3 weeks each. Birds were unstimulated until day 100, under dim LL (dl:dl) and 12dl:12dk. Photostimulation with a significant increase (p less than 0.001) in average body weight and testis volume occurred on exposure to 12bl:12dl (10:2 lux); birds remained fat and testes were enlarged until the end (day 173) of the experiment. Locomotor activity also did not have a discernible pattern under the nongonadostimulatory photoregimes. Birds became active in the bright photophase (subjective day) of 12bl:12dl (10:2 lux) on day 5 (day 105 of the experiment), but beginning on day 113 more intense perch-hopping was initiated in the dim photophase (subjective night), indicating the appearance of nocturnal migratory restlessness in the caged birds. A 180 degrees transition in the bl:dl photophases at this time for 2 weeks resulted in complete shift in the timing of daytime and nighttime activity. This trend is maintained under all subsequent 12bl:12dl exposures. These results suggest that the light intensity required for photostimulation in the blackheaded bunting is absolute, and that the subjective interpretation of day and night depends upon the photophase contrast, as well. PMID- 1641424 TI - Determinants of the slow acquisition of medical and sulcal prefrontal cortex self stimulation: an individual differences approach. AB - Stimulation-naive rats were tested for motor activity during noncontingent electrical stimulation of the medial prefrontal cortex (MPC) or sulcal prefrontal cortex (SPC). Defecation during stimulation was also measured. The rats were then tested using a conditioned taste aversion paradigm for aversion to a novel flavor (0.1% saccharin) paired with stimulation. Finally, the rats were trained to acquire self-stimulation over 26 days of training. Large individual differences were seen in motor activity, defecation, and conditioned taste aversion to initial stimulation and in the subsequent speed of self-stimulation acquisition. In the MPC-stimulated group, acquisition speed was positively correlated with motor activity to initial stimulation and negatively correlated with defecation to this stimulation. In the SPC-stimulated group, the same correlations were evident, but only when rats suffering seizures prior to self-stimulation acquisition were excluded from the analysis. Such preacquisition seizures, which were only found in the SPC-stimulated group, retarded self-stimulation acquisition. In most rats, MPC or SPC stimulation failed to condition a taste aversion to saccharin. These results suggest that the slow acquisition of MPC and SPC self-stimulation may be partly related to the motor suppressive, aversive, and convulsive properties of initial stimulation. PMID- 1641425 TI - Acceleration of tail pinch-induced feeding in rats by analgesic effect of neurotropin. AB - Mechanisms of tail pinch-induced feeding and effects of neurotropin (NSP), an extract from the inflamed skin of rabbit inoculated with vaccinia virus, on behavioral responses were investigated in rats. Treatment of a 5-min tail pinch (tail pinch I) induced feeding response. An intensified 15-min tail pinch (tail pinch II) provoked emotional reactions besides feeding behavior. The rate of food intake (food intake/tail pinch duration) during tail pinch II was less than that at tail pinch I. Intraperitoneal administration of NSP (100 mg/kg/day) by itself produced no remarkable change in feeding or emotional behavior. However, NSP treated rats increased eating size and prolonged eating duration during tail pinch I. Pretreatment of NSP increased feeding behavior more potently at tail pinch II than at tail pinch I and decreased the incidence of emotional reactions at tail pinch II. The results suggest that NSP, by its analgesic action, may modulate behavioral responses during tail pinch treatment through selective blockade of the nociceptive and feeding-inhibitory information, but not through the nonnociceptive and feeding-excitatory signals. PMID- 1641426 TI - Mimicking corticosterone's daily rhythm with specific receptor agonists: effects on food, water, and sodium intake. AB - The endogenous pattern of type I and II corticosteroid receptor stimulation was systematically assembled from specific agonists in order to detect any unique receptor interactions in the control of ingestive behavior. The type II agonists dexamethasone (0, 5, or 25 micrograms/kg) or RU28362 (0, 5, or 25 micrograms/kg) were injected daily in the final hour of the light phase of the illumination cycle of adrenalectomized rats. This was carried out in the presence or absence of continuous aldosterone (type I agonist) infusion. Additional comparisons were made with sham-operated groups and animals receiving type II agonists by continuous infusion. Type II agonists increased the intake of 2% saline and the proportion of food taken at night, but had negligible effects on total food intake. Type II agonists did not interact with the type I agonist. Type II effects were greatly potentiated by continuous infusion, though administered at the same doses as acute injection. When the effects of type II receptor stimulation emerged, they always consisted of an exacerbation of the adrenalectomy syndrome, not a return to normal quantities or patterns. In contrast, type I receptor stimulation restored both the quantities and unique day night patterns of saline, water, and food intake to values matching intact animals. The findings suggest that the behavioral significance of corticosterone's nocturnal peak of type II stimulation is small, and that its most important function may lie in the metabolic processes it instigates during its steady rise in the light phase. PMID- 1641427 TI - Neuropeptide Y paradoxically increases food intake yet causes conditioned flavor aversions. AB - Neuropeptides have been implicated in the short-term regulation of food intake and the long-term control of body weight. Previous studies have shown that central administration of neuropeptide Y (NPY), the most abundant of these peptides in the brain, produces robust increases of food intake. We now report that NPY, at doses that stimulate food intake when administered intraventricularly, also causes the formation of robust conditioned flavor aversions when given via the same cannula and at the same dose. This apparently paradoxical effect may be indicative of different populations of central NPY receptors having dissimilar effects on ingestive behaviors. The results also suggest that the use of conditioned aversions to investigate drug-induced malaise may not be appropriate when applied to ingestive behaviors. PMID- 1641428 TI - A possible genetic association between PROP-tasting and alcoholism. AB - Fifty-five young adult subjects and their parents were classified as alcoholic or nonalcoholic based on a standardized questionnaire (the MAST) filled out by the subjects. Subjects' thresholds for detection of 6-n-propylthiouracil (PROP; a PTC like compound) were determined with the experimenter blind to MAST responses. There was a significantly higher proportion of nontasters of PROP among children of alcoholics than among children of nonalcoholics. There was no relationship between the child's alcoholism status and ability to taste PROP. These results are inconsistent with the view that excessive use of alcohol causes the association between nontasting and alcoholism and are consistent with the view that there is a genetic association between PROP/PTC-tasting and alcoholism. PMID- 1641429 TI - Intraperitoneal administration of recombinant human interleukin-1 beta inhibits osmotic thirst in the rat. AB - Decrease in water intake after intraperitoneal injection of interleukin-1 beta (IL-1 beta) was studied in the rat. Administration of IL-1 beta at a dose of 20 micrograms/kg attenuated osmotic thirst induced by intraperitoneal injection of hypertonic saline, but did not affect hypovolemic thirst induced by subcutaneous injection of either polyethylene glycol or angiotensin II. Interleukin-1 beta also decreased spontaneous intake of water but not that of 1.8% saline. The results suggest that the decrease in water intake by IL-1 beta is caused, at least in part, by suppression of osmotic thirst but not by general suppression of behavior. The effects of IL-1 beta were not secondary responses accompanied by feeding behavior, since food supply was removed during the experiments. Pretreatment with indomethacin blocked the decrease in water intake by IL-1 beta, suggesting the involvement of production of prostaglandins. PMID- 1641430 TI - Contribution of the amygdala to learning and performance of conditional fear. AB - The amygdaloid complex appears to be an essential component in the neural systems mediating some forms of aversive Pavlovian conditioning. The relative contribution of this structure to acquisition and performance during fear conditioning was assessed by making temporary lesions in the amygdala prior to training or retention testing in a single-trial Pavlovian conditioning preparation. Microinjection of lidocaine HCl (5.0%, 1.0 microliters) into the amygdala prior to the presentation of a CS signalling footshock resulted in a significant attenuation of the performance of conditional fear, as indexed by the amount of time rats spent engaged in defensive freezing behavior during the retention session. However, similar treatment with lidocaine prior to the training session, during which the CS and UCS were paired, resulted in only a weak reduction in subsequent responding. Thus, while both acquisition- and performance-related processes take place within the amygdala, it appears that the latter are more sensitive to disruption using the present procedures. These results are discussed in terms of the general role played by this structure in aversive learning and motivational processes. PMID- 1641431 TI - Oral estrogen retains potency as an aversion agent in eggs: implications to studies of community ecology and wildlife management. AB - The first of two experiments with laboratory rats demonstrated that oral estrogen (17 alpha-ethinylestradiol) can remain in the albumen of eggs at room temperature for up to 8 days with undiminished capacity to produce conditioned taste aversion. The second experiment showed that estrogen remains potent in the yolk of eggs for at least 4 days. There is now greater assurance that egg prey placed into the field will induce reliable CTA among mammalian predators. Community ecologists interested in such processes as competitive release and the responses of prey populations to reduced predation upon their eggs can selectively factor predation out of field experiments without the need for physically excluding predators. Wildlife biologists interested in reducing predation upon the eggs of endangered species now have greater assurance that estrogen-treated egg baits will suppress predation in a more cost-effective manner and with less likelihood of discrimination between treated eggs and those of endangered species. PMID- 1641433 TI - Cancer screening intervention among black women in inner-city Atlanta--design of a study. AB - This experimental study attempts to determine if an in-home educational intervention conducted by lay health workers (LHWs) can increase adherence among low-income, inner-city black women to schedules for screening for breast cancer and cervical cancer, as well as increase the women's knowledge and change their attitudes regarding these cancers. This paper is a description of the purposes, hypotheses, design, subject recruitment, intervention, and evaluation of the study conducted by Morehouse School of Medicine. Subjects were recruited from a variety of sources, including patients seen in a community health center, women referred by the National Black Women's Health Project (NBWHP), residents of public and senior citizen housing projects, and persons identified in various community settings. Fewer than half of those asked to participate agreed to do so. The 321 women who were recruited were demographically diverse. Overall, about half of these volunteer subjects self-reported at least one Papanicolaou (Pap) smear and one breast examination within a year before enrollment in the study. There was little variation by source of recruitment in compliance with screening recommendations, except that referrals from NBWHP were more likely (P less than 0.01) to have had a Pap test and breast self-examination, while residents of public housing projects were somewhat less likely to have done so. About 35 percent of participants ages 35 and older had a mammogram within an appropriate interval. Participants were randomly assigned to intervention and control groups. Women in the intervention group were visited in their homes by LHWs on three occasions; the LHWs provided education on cancer and reproductive health. The groups were comparable in their baseline sociodemographic status and previous screening history. PMID- 1641432 TI - Multistrategy health education program to increase mammography use among women ages 65 and older. AB - Mammography use decreases with age although the risk of breast cancer increases with age. Medicare now provides biennial coverage for screening mammography. This study was designed to simulate the Medicare condition by subsidizing mammography among women in eight retirement communities in the metropolitan Philadelphia area. The study also measured the impact of health education interventions and the presence of a mobile mammography van on increased use of mammography. Retirement communities were assigned randomly to the control (cost subsidy alone) or experimental group (cost subsidy, mammography van, and tailored health education interventions). A total of 412 women ages 65 and older who had not had mammograms in the previous year were surveyed at baseline and 3 months later. Analytic techniques reflected the cluster nature of the randomization. Women in the experimental group were significantly more likely than the control group women to have obtained mammograms. Forty-five percent of the experimental group women compared with 12 percent of the control group women subsequently had mammograms in the 3 months after the baseline interview (P less than .001). Logistic regression analysis for mammography use indicated an odds ratio of 6.1 associated with being in the experimental group. For women in the experimental group, a separate logistic regression for mammography use showed an odds ratio of 7.8 associated with attendance at the educational presentation. The results suggest that Medicare coverage alone will not increase mammography use sufficiently to achieve year 2000 objectives. However, the addition of access enhancing and health education interventions boosts utilization dramatically. PMID- 1641434 TI - Effects of migration on cancer incidence and resources for prevention and treatment in Florida. AB - Migration adds a complex dimension to the task of those who plan and allocate resources for health care. The authors offer a methodology for estimating the contribution of migration to the incidence of cancer, allow for age- and sex specific cancer risks, and estimate, by country, the impact of recent migration on the annual incidence of cancer in Florida. Cancer and migration data were used to develop estimates of the number of cancer cases for Florida counties that were attributable to recent migrants. A net gain and loss ratio was calculated for new cancer cases in 1980 resulting from the 1975-80 migration pattern. Florida data was used because that State has one of the highest crude cancer incidence rates in the nation, is one of the most populous States, and has a population growth from migration rather than from natural increase. Preliminary findings on the relationship between cancer health services resources and net cancer rates from migration are discussed. County cancer health services resources had a strong positive relationship to population size, but the impact of migration on cancer incidence was in a curvilinear relationship to population size. PMID- 1641435 TI - Accessing NCI's SEER cancer data base with SeerQuery and CD-ROM. AB - The National Cancer Institute operates the Surveillance, Epidemiology, and End Results (SEER) cancer data base. SEER data are obtained from participating population-based registries that monitor cancer incidence and patient survival in a representative 10 percent sample of the general population. The data cover all cancers (except superficial skin cancers) in the defined regional populations. SeerQuery is a personal computer program for accessing that data on IBM compatible personal computer compact diskettes in read-only memory (CD-ROM) form. SeerQuery facilitates rapid access to cancer data at minimal cost and effort to the user. SeerQuery is menu-driven, enabling physicians and other health care professionals to query the data base directly. They can use the data to determine cancer frequency, perform cross-tabulation, determine incidence, and calculate survival using such variables as primary cancer site, histologic type, stage, sex, age, and race. The comprehensive data base lacks many selection biases that are inherent in data reported from other sources. SeerQuery has applications in professional education and in cancer control program planning and resource allocation. PMID- 1641436 TI - Descriptive epidemiology of unintentional residential fire injuries in King County, WA, 1984 and 1985. AB - Although most studies have concentrated on fatal residential fire injuries, which are a leading cause of fatal injuries in the United States, few investigators have examined in detail nonfatal injuries as a consequence of residential fires. This population-based study used the Washington State Fire Incident Reporting System to assess the incidence and descriptive epidemiology of fatal and nonfatal burns or respiratory tract damage resulting from unintentional residential fires. For the 2-year period 1984-85 in King County, WA, the mortality rate due to injury in a residential fire was 0.7 per 100,000 per year, and the incidence of nonfatal injuries was 5.6 per 100,000 per year. Of 17 fatalities, 59 percent of the deaths occurred at the scene of the fire. Of 128 persons with nonfatal injuries, 19 percent were hospitalized; although the 55 percent seen as outpatients and the 26 percent treated by the fire department or paramedics at the fire scene usually had minor injuries, they would not have been captured if only traditional data sources had been employed. Those injured averaged 2.8 days of restricted activity, but the range was from less than 1 day to 1 year. Injuries were more common in the households with a low socioeconomic status and among nonwhites, especially American Indians. Variation in incidence by age, sex, and source of ignition for deaths and nonfatal injuries suggests appropriate targets for future fire injury prevention programs. PMID- 1641437 TI - Hospital and community characteristics in closures of urban hospitals, 1980-87. AB - Characteristics of 190 urban community hospitals that were closed during the period 1980-87 and characteristics of the communities that they served were analyzed and compared to a control group of 380 urban hospitals that remained open. A negative association was found between hospital closure and four hospital characteristics: the presence of a cancer program approved by the American College of Surgeons, the combined characteristics of for-profit status and membership in a multi-institutional chain, the number of admissions, and the number of facilities and services offered. A positive association was found between hospital closure and the percentage of black residents in the community. These findings are discussed in the context of political and economic trends in health care and urban development. Implications for future research are noted, including managerial strategy for hospital administrators and the socioeconomic implications of hospital survival in declining urban communities. PMID- 1641438 TI - Participant evaluation and cost of a community-based health promotion program for elders. AB - There is little information on how best to provide health promotion and disease prevention services to elderly persons. This paper reports participants' perceptions of the effectiveness of a health promotion program consisting of health education classes and case management services. A single-group, posttest only design was used for the county-wide program, which operated independent of participants' primary care physicians. Each person received a thorough screening evaluation, was invited to health education classes, and was assigned a case manager for a 2-year health promotion period. Community residents 64-71 years of age were recruited; 475 entered the study, and 378 (79.6 percent) completed the followup evaluation interview. Only one-third of the participants attended at least one class, but a majority of those attending each class rated it very or extremely effective in increasing knowledge. To determine the effectiveness of the case managers, each participant identified the three health problems that were of greatest concern to him or her and indicated which of these priority problems were discussed with the case manager. Discussion with the case manager was significantly associated with continuing to see a personal physician for the problem, following the physician's recommendations, the problem's being under control, and the problem's improving over the 2-year followup. The classes and case management services benefited the participants who used them. How to best deliver these services to the target group needs further study. PMID- 1641439 TI - Exploratory study of the relationship between hypertension and diet diversity among Saba Islanders. AB - The relationship between diet diversity and hypertension was examined in a cross sectional exploratory study of 82 randomly selected adult residents of Saba Island, Netherlands Antilles, in the eastern Caribbean Basin. Blood pressure measurements, taken over 4 years, and the appropriate use of antihypertensive medications, were used to identify chronic hypertensives. A 24-hour dietary recall, semi-quantitative food frequency interviews, and ethnographic confirmation techniques were used to calculate diet diversity, a measure of the overall dietary pattern. Results suggest hypertension is associated with lack of an overall balance of food groups in the daily diet beyond any imbalance of a particular dietary cation such as sodium, potassium, or calcium. Bivariate analyses found a significant association between a poorly diversified diet and hypertension (odds ratio [OR] = 4.25, 95 percent confidence intervals [CI] = 1.47,12.30). Dietary intake of sodium, potassium, and calcium was also examined and found not to be associated with the presence of hypertension in bivariate analyses. Including these cations individually in logistic regression models, which also included diet diversity, did not diminish the diet diversity hypertension association. Multiple logistic regression models in which other potential confounding variables were individually entered as a control variable (body fat, skin color, age, sex, perceived stress, alcohol intake, aerobic activity, and socioeconomic status) did not alter this result. Analysis of the presence or absence of individual food groups indicate a lack of legumes in the daily diet is also associated with the diagnosis of hypertension (OR = 4.71, 95 percent CI = [1.71,13.01]). PMID- 1641440 TI - The neglected health care needs of street youth. AB - Juveniles who live on the street are often the victims of physical and sexual abuse and family chaos. They have a multitude of health problems such as malnutrition, respiratory infections, sexually transmitted diseases, including human immunodeficiency virus, mental illness, and substance abuse. Health care, if available, is generally fragmented and often not relevant to their needs. Their high-risk existence leads to individual morbidity and has a negative effect on the health of the community. Presently, there is limited research on the health status and health care needs of street youth who are difficult to track and quantify. The findings of a project undertaken by Region IX of the Public Health Service in 1989 to provide technical assistance to three primary care clinics serving street youth in San Francisco are reviewed. Data were collected on demographics, overall health status, sex-related medical problems, mental health, and substance abuse and compared with another group of adolescents in the general population. Street youth were found to have a greater number of problems- both physical and psychological--than the general adolescent population. High risk behaviors, such as drug abuse and failure to use condoms during sex, make this population especially vulnerable to sexually transmitted diseases, including human immunodeficiency virus. The potential impact on public health is enormous. Adequate access to health services needs to be addressed legislatively. PMID- 1641441 TI - Cholesterol treatment practices of primary care physicians. AB - The active involvement of primary care physicians is necessary in the diagnosis and treatment of elevated blood cholesterol. Empirical evidence suggests that primary care physicians generally initiate dietary and pharmacological treatment at threshold values higher than is currently recommended. To determine current treatment thresholds and establish factors that distinguish physicians who are more likely to initiate therapy at lower cholesterol values, 119 primary care physicians in four northern California communities were surveyed. Data collection included their demographic factors, treatment of hypothetical patients, self efficacy regarding counseling patients about cholesterol reduction and personal health behaviors, outcome expectations, and cholesterol knowledge and attitudes. Results indicated that 59 percent of respondents would not start dietary treatment on a middle-aged female patient with a cholesterol of 215 milligrams per deciliter (mg per dl). Only 44 percent of respondents indicated that they would initiate pharmacological therapy for a middle-aged man with a cholesterol of 276 mg per dl. Logistic regression models were used to determine characteristics that influenced dietary and pharmacological treatment practices. Younger physicians, those who had had their own cholesterol checked, and those who personally ate a low-fat diet, were more likely to recommend diet therapy to patients with modest elevations of cholesterol. Willingness to use lipid lowering medications at more marked elevations was associated only with increased self efficacy regarding use of drugs to lower cholesterol. These results indicate that physicians' personal health behaviors and self-efficacy should be addressed in interventions to modify cholesterol-related practice behavior. PMID- 1641442 TI - Using the Behavioral Risk Factor Surveillance System to monitor year 2000 objectives among American Indians. AB - The Behavioral Risk Factor Surveillance System, a data set based on telephone surveys that have been conducted by States in collaboration with the Centers for Disease Control, has been used to estimate the prevalence of behavioral risk factors for adults in the United States so health objectives can be set and progress towards accomplishing them measured. Data for adult American Indians in this regard have not been available generally. The use of these data to estimate behavioral risk prevalence for American Indians by geographic region was examined and the results compared with those for white Americans. In addition, data from the system were compared with other data sets, including the results of selected surveys in American Indian communities, to explore the validity of the system as a tool for evaluating the behavioral risks of Indians. Behavioral Risk Factor Surveillance System data for the period 1985 to 1988 were used. During this period, the 1,055 American Indian respondents constituted 0.63 percent of those responding under the system and 0.70 percent of the population of the participating States. Separate (sex-specific) behavioral risk prevalence estimates were derived for Indians and whites for four geographic regions- Southwest, Plains, West Coast, and Other States. The system's behavioral risk estimates for the Plains region were compared with available data from behavioral risk surveys done in three American Indian communities in Montana (Blackfeet, Fort Peck, and Great Falls) from 1987 to 1989. The behavioral risk factors compared include use of automobile seatbelts, current smoking, current use of smokeless tobacco, heavy drinking, drinking and driving, overweight, hypertension, and sedentary lifestyle. Although large regional differences in the prevalence of these risk factors were found, the magnitude and direction of the differences are frequently similar among American Indians and whites living in the same geographic regions. The findings from the Behavioral Risk Factor Surveillance System among American Indians are largely consistent within dependently collected data from more resource intensive household surveys, at least when surveys in Montana are compared with system data from the Plains. These data are generally consistent with other epidemiologic studies.When they are used in conjunction with community-specific surveys, the Behavioral Risk Factor Surveillance System data may be useful for monitoring the progress of American Indians towards the Year 2000 national health objectives. The value of the surveillance system for monitoring trends in behavioral risk factors among Indians would be enhanced if States attempted to over sample regions (such as Indian reservations) with a high proportion of Indian residents. It appears that aggressive health promotion and disease prevention efforts will be needed if these objectives are to be achieved. PMID- 1641443 TI - Life expectancy by employment status, income, and education in the National Longitudinal Mortality Study. AB - Based on data from the National Longitudinal Mortality Study for 1979-85, life expectancies are estimated for white men and white women by education, by family income, and by employment status. Life expectancy varies directly with amount of schooling and with family income. Differences in life expectancy at age 25 between the highest and the lowest levels of education completed were about 6 years for white men and about 5 years for white women. For family income, differences between the highest and the lowest income groups were about 10 years for white men and 4.3 years for white women. The largest differences in life expectancy were between employment categories. At age 25, white men in the labor force lived on average about 12 more years than those not in the labor force, and white women lived on average about 9 more years. For those who were unable to work compared with those in the labor force, the difference for white men was about 20 years; for white women, 29 years. Results in this study showed much the same differentials in life expectancy for education as the earlier Kitagawa Hauser study. PMID- 1641444 TI - HIV infection treatment costs under Medicaid in Michigan. AB - The Michigan Medicaid Program payment records generated in the period 1985-89 by 783 persons were analyzed for services related to human immunodeficiency virus (HIV) infection. Other data from death records and the Michigan AIDS Surveillance Registry were available for a subset of those persons. The average monthly payment in 1989 dollars for HIV-related services was $1,302.57. Services determined to be unrelated to HIV infection accounted for 12.5 percent of the total amount for health care received and another 2.5 percent was questionable. The average monthly expenditure for men was roughly twice that for women. The discrepancy did not exist among persons identified in the AIDS Surveillance Registry. Sex differences ceased to exist when Medicaid eligibility (disability versus Aid to Families with Dependent Children) was controlled for by analysis of variance. There were no significant differences between payments to those infected through male-to-male sexual contact and those infected through intravenous drug use. Payments for HIV treatments rose with age to about 40 years, and declined slightly among older adults. The sharpest rise was for those ages 19-25 years and 26-35 years. Large sex differences existed among those who received zidovudine (AZT), 61.4 percent of the men and 19.1 percent of the women. Controlling for Medicaid eligibility moderated those differences, but they remained statistically significant. Differences in zidovudine usage were not found between men and women in the subset identified in the AIDS Surveillance Registry nor among persons infected through male-to-male sexual contact and intravenous drug use. PMID- 1641445 TI - Inappropriate lubricant use with condoms by homosexual men. AB - Use of condoms has been advocated as an important method of reducing the risk of human immunodeficiency virus (HIV) transmission among high-risk groups such as homosexual and bisexual men, prostitutes, intravenous drug users, adolescents, and hemophiliacs. Despite risk-reduction education campaigns directed to gay men since the early 1980s, evidence shows continued deficits in condom-use skills and knowledge among gay men. Because most failures in the use of condoms are attributed to errors in use, increasing knowledge and skills in condom use is important in preventing HIV infection. Two groups of homosexual and bisexual men were sampled, those entering a risk-reduction education program and participants in a Gay Pride event. They were surveyed on their current sex practices and their efforts to reduce their risk of HIV infection. They were asked about their numbers of sex partners, specific sexual behaviors, use of condoms, types of condoms used, and lubricants used for genital-anal sex. The characteristics of those surveyed were similar to those of respondents in other studies of risk reduction among gay men. The use of an oil-based lubricant with condoms has been shown to weaken latex and to increase the likelihood of condom breakage, which use of water-based lubricants does not. Among respondents who reported having genital-anal sex, 60 percent reported use of an oil-based lubricant with a condom at least once during the year before the survey. Gay men in sexually exclusive relationships engaged in less consistent use of condoms for receptive genital anal sex than did single gay men. The duration of their relationship with a partner was unrelated to the consistency of risk reducing behaviors practiced by men in sexually exclusive relationships. Gay Pride participants engaged in sexual behavior that was relatively more risky for HIV transmission than did the other group. Gay Pride participants used condoms less consistently for genital-anal sex than did the risk-reduction program entrants.The findings indicate the need for better risk reduction education efforts directed to gay men. Continued improvement in these efforts will require assessing the effectiveness and consistency of risk reduction efforts, determining the potential for gay men to relapse into more risky behavior, and identifying gaps in the knowledge of risk reduction efforts among gay and bisexual men. Risk reduction programs need to emphasize motivational factors, provide basic information on how one determines the content of lubricants, explain why water-based lubricants only should be used, and teach how to use condoms properly. Active outreach is needed to gay and bisexual men who are unlikely to voluntarily enroll in risk-reduction programs. PMID- 1641446 TI - Timeliness of notification in infectious disease cases. AB - Records of notification in cases of eight infectious diseases in the "Servei Territorial de Salut Publica" of the Province of Barcelona, Spain, between 1982 and 1986 were reviewed. Time from onset of symptoms to notification, time from notification to completion of data collection, and time from onset to completion of the case investigation were analyzed. For the period from onset to notification, the shortest mean was registered for meningococcal infection (6.31 days) and the longest was for pulmonary tuberculosis (54.79 days). For time from notification to complete investigation, the shortest value was for pulmonary tuberculosis (12.20 days) and the longest for rickettsioses (35.79 days). Time from onset to completion of data collection was 22.87 days for meningococcal infection and 72.34 days for tuberculosis of other organs (probably because of the long period of time that elapses between the onset of the first symptoms and notification). It would appear that both physicians and the general population must be educated so that lay-men can identify early signs and symptoms of disease and physicians can realize that statutory notification of infectious diseases is strongly linked to community health care. PMID- 1641447 TI - An outbreak of Bacillus cereus food poisoning--are caterers supervised sufficiently. AB - Bacillus cereus is an uncommonly reported cause of foodborne illness in the United States. In May 1989, an outbreak of B. cereus gastroenteritis occurred among 140 guests who had attended a catered wedding reception in Napa, CA. Investigation established Cornish game hens served at the event as the vehicle for disease transmission (OR = 29, P = 0.0001). Although the spores of B. cereus are ubiquitous, large numbers of toxin-producing organisms (more than 10(5) per gram of food) are required for illness to occur. In the Napa outbreak, bacterial multiplication was facilitated at several points during the preparation and transportation of the food. While a licensed restaurant kitchen was used, the facilities were clearly inadequate for the event. At present, the California Health and Safety Code does not address the scope of catering operations. As caterers increase in number, there will be a growing need for governmental oversight to ensure that food production on a large scale is conducted safely. PMID- 1641448 TI - Use of death certificates for mesothelioma surveillance. AB - Data from the Massachusetts Cancer Registry and death certificates were linked for mesothelioma cases reported to the registry from 1982 through 1987 to determine the extent to which the cause of death information that is given on the death certificate is useful in identifying mesothelioma cases for disease surveillance. Only 12 percent of all persons reported with mesothelioma who had died were detected using underlying cause of death codes for cancers of the peritoneum and pleura, which are commonly used to identify mesothelioma cases. The rate increased to 83 percent when death certificates were reviewed manually for any mention of mesothelioma. Surveillance using only the coded cause of death data currently available will result in a large underascertainment of mesothelioma cases. PMID- 1641449 TI - Johnson Foundation booklet describes AIDS care projects in 11 communities. PMID- 1641450 TI - Cervical enamel projection with gingival fenestration in a maxillary central incisor: report of a case. AB - Bacterial plaque has been implicated as the primary etiologic factor in the initiation and progression of periodontal disease. Anatomic factors, such as cervical enamel projections, enamel pearls, and radicular grooves, are often associated with advanced localized periodontal destruction. Enamel projections and pearls are most often associated with molars, while radicular grooves are usually located on the palatal aspect of maxillary incisors. Gingival fenestrations are of uncertain etiology and have rarely been reported in the dental literature. An unusual case is presented of a cervical enamel projection located on the facial aspect of a maxillary central incisor in association with gingival fenestration. Rationale for therapy and likely healing results are discussed. PMID- 1641451 TI - Computer-designed inlays after 5 years in situ: clinical performance and scanning electron microscopic evaluation. AB - Eight mesio-occlusodistal adhesive inlays, fabricated from ceramic blocks using a computer-aided design/machining method, were reexamined after 5 years of clinical service. The inlays wre evaluated according to modified US Public Health Service criteria. The results indicated excellent clinical performance, with eight Alfa ratings for wear, recurrent caries, and color match, and five Alfa and three Bravo for marginal discoloration and marginal integrity. Under scanning electron microscope, 81.0% of the tooth-cement interfaces and 84.1% of the cement-inlay interfaces were rated continuous at the occlusal margin. Axially, 73.6% of the tooth-cement interfaces and 87.0% of the cement-inlay interfaces were rated continuous. Although this long-term investigation revealed good clinical performance of the inlays, improvements in the ceramic structure and its properties, the cavosurface design, and the luting composite resin were recently introduced to further optimize quality. PMID- 1641452 TI - Excimer lasers in dentistry: future possibilities with advanced technology. AB - The thermal side effects of carbon dioxide and neodymium:yttrium-aluminum-garnet lasers limit their clinical applications. These high-powered, infrared lasers result in zones of charring and carbonization even in soft tissues and the bone. In contrast, the pulsed, ultraviolet radiation emitted by excimer lasers causes limited thermal, denaturative damage to surrounding tissues. Therefore, treatment of dental tissues with the nonthermal process of photoablation with excimer lasers may present alternatives to traditional dental practice. Possible future applications of the excimer laser include selective caries removal, the conditioning of tooth surfaces, and cleaning of root surfaces; the zones of necrosis are small, so that there is no residual debris. PMID- 1641453 TI - The in vitro effect of glass-ionomer cement restoration on enamel subjected to a demineralization and remineralization model. AB - The purpose of this in vitro study was to evaluate differences in initiation and progression of carieslike lesions around restorations in enamel. A demineralization/remineralization cycling model was used to induce experimental secondary caries around cavities restored with glass-ionomer cement or composite resin. The effects of these materials were compared by microhardness profiles. The results indicated that glass-ionomer cement showed potential value as a restorative material for the prevention or reversal of caries in enamel adjacent to restorations, even in situations of high cariogenic challenge. PMID- 1641454 TI - Modified internal bleaching of severe tetracycline discoloration: a 6-year clinical evaluation. AB - Since 1985, 534 severely discolored teeth have been treated with intentional endodontics and internal bleaching; of these, 258 were treated with the conventional technique and 276 were treated with the modified technique. Six years of clinical and radiographic evaluation revealed that the results obtained with the first group (conventional technique) remain stable and that a very noticeable improvement has been achieved with the second group of teeth, treated with the modified technique. PMID- 1641455 TI - Improved esthetics with a combined bleaching technique: a case report. AB - This paper describes a clinical case in which a combination bleaching technique was used to improve the appearance of the patient's discolored anterior teeth. Enamel microabrasion was used first to remove superficial fluorosis stains. A home bleaching regimen was then used to lighten the overall shade of the teeth, which had appeared more yellow after microabrasion. PMID- 1641456 TI - Management of rampant caries in children. AB - Because research has resulted in a better understanding of the etiology of dental caries as well as the introduction of new techniques and materials in the practice of dentistry, approaches toward the management of rampant caries should be reevaluated. The development of the acid-etching technique and the improvements in the physical properties and clinical performance of composite resins and glass-ionomer cements have completely changed the concepts of prevention, conservative dentistry, and dental esthetics. Several methods for the treatment of rampant caries are described and management of two cases is documented. PMID- 1641457 TI - The rationale and indications for equilibration in the primary dentition. AB - One type of malocclusion in the primary dentition is posterior crossbite caused by premature deflective occlusal interferences. The primary canines are the teeth that most frequently contribute to a laterally guided centric occlusion that creates a functional malocclusion. Because this is not a self-correcting situation, these types of posterior crossbites should be identified early and evaluated for possible correction through occlusal equilibration. A case that illustrates early correction of a unilateral functional posterior crossbite by equilibration and the 5-year results are presented. PMID- 1641458 TI - Enamel microabrasion: a microscopic evaluation of the "abrosion effect". AB - Enamel surfaces have been found to acquire a glasslike luster and an exceptionally smooth texture following enamel microabrasion procedures. A commercially available enamel microabrasion compound containing abrasive particles and a mild concentration of hydrochloric acid, when applied by rotary compression, simultaneously abrades and erodes (abrosion) the enamel surface. Human enamel surfaces were evaluated microscopically after routine enamel microabrasion procedures. The results show distinct evidence of enamel surface changes that have been described as the abrosion effect. PMID- 1641459 TI - Clinical evaluation of a new pressed glass ceramic inlay material over 1.5 years. AB - Ten IPS/Empress pressed glass ceramic inlays were cemented in box-shaped, non beveled, Class II, posterior cavities. They were evaluated clinically according to modified US Public Health Service criteria after 1.5 years in vivo. In addition, quantitative marginal analysis was performed immediately after placement of the inlays and at the 1.5-year recall. Clinical evaluation revealed that the inlays performed well after 1.5 years; all inlays received scores of Alfa or Beta for all criteria evaluated. Scanning electron microscopic examination indicated that the excellent initial marginal adaptation decreased significantly over 1.5 years. PMID- 1641460 TI - The effectiveness of an enzyme-containing denture cleanser. AB - The purpose of this study was to test the effectiveness of an enzyme-containing denture cleanser. During a 3-week period, 13 patients used Enzydent only for soaking the denture; during another 3-week period, the patients were instructed first to soak and then to brush their denture. The effectiveness of the cleanser was measured by microbiologic procedures. The results showed that soaking the denture in the enzyme-containing cleanser alone was as effective as the patients' previous regimen of denture hygiene, but that when soaking was used in combination with brushing, the denture became significantly cleaner. PMID- 1641461 TI - Postoperative infections and tetracycline prophylaxis in periodontal surgery: a retrospective study. AB - The aims of this retrospective study were to assess the incidence of infection after periodontal surgery, in relation to the type of surgical procedure, and the effectiveness of prophylactic tetracycline administration. Nineteen (4.4%) of 445 surgical procedures in patients who were given no tetracycline resulted in signs of infection, while two (3.8%) in patients who were treated with tetracycline resulted in signs of infection. There was no statistically significant difference between these incidences, suggesting that there is no reason for routine tetracycline prophylaxis in periodontal surgery. There was no statistically significant difference in the incidence of infection whether or not bone (ostectomy or osteoplasty) or tooth extraction was involved in the surgical procedure. PMID- 1641462 TI - Effect of protraction headgear on Class III malocclusion. AB - Ten patients with skeletal Class III malocclusion in the early mixed dentition who were treated with maxillary expansion appliance and protraction headgear were compared with reasonably matched controls. Significant orthopedic effects were found after as little as 6 months of treatment. Cephalometric analysis revealed that the correction of Class III malocclusion was primarily a result of forward and downward movement of the maxilla and backward rotation of the mandible. The clinical result of one patient treated with this appliance is used to demonstrate the importance of force magnitudes and directions, as well as the design of the appliance, to the success of the treatment. PMID- 1641463 TI - The effect of early water contact on glass-ionomer cements. AB - The purpose of this study was to observe the effect of immersion in water at 3, 5, 7, and 10 minutes after mixing on the surface of three regular and one light curing glass-ionomer cements by measuring penetration of a methylene blue solution. Early solubility of these cements was also measured and compared with that of a zinc phosphate and a polycarboxylate cement. A blue-stained zone was observed in all glass-ionomer cements, but an inner, opaque zone was observed in only two of the regular glass-ionomer cements. Extending the time between start of mixing and immersion in water decreased the width of both zones in all cements and markedly lowered the loss of substance from the surface of regular glass ionomer cements. However, time after mixing had no or only a limited effect on the loss of substance from the light-curing glass-ionomer cement, the zinc phosphate cement, or the polycarboxylate cement. PMID- 1641464 TI - Influence of sterilization on the corrosion resistance of high-speed dental handpieces. AB - Ball bearings of high-speed dental handpieces were sterilized by various procedures and examined under scanning electron microscopy for evidence of corrosion. The metallic parts of ball bearings (rings and spheres), if not correctly lubricated, were dramatically corroded in chemical vapor and steam sterilizer. The nonmetallic parts (the retainers made of phenolic resins) appeared to be more sensitive to heat treatments, as revealed by the occurrence of darkening and embrittlement phenomena. In the absence of correct lubrication procedures, the performance of high-speed dental handpieces appears to be adversely influenced by sterilization, mostly in wet environments. On the other hand, daily maintenance that follows the manufacturer's instructions reduces and delays the damage to a great extent. PMID- 1641465 TI - Failla Memorial Lecture. Is radiation all bad? The search for adaptation. PMID- 1641466 TI - Transient thermal and mechanical response of water subject to ionizing radiation. AB - The ultrafast transient (10(-14) to 10(-12)S) thermal and mechanical response of water subject to ionizing radiations of different linear energy transfers has been investigated in order to understand the initial events which lead to cell mutation and lethality. Based on computational fluid dynamics, the production of a "thermal spike" around the trajectory of a charged particle and subsequent diffusion of deposited heart are calculated for particles with linear energy transfer (LET) of 4, 40, and 400 keV/microns. A radiation damage region (that is, the so-called "thermal core") is identified, and the transient behavior of the thermal core is studied. The local and transient environment has a dimension of nanometers, a scale which is of critical interest in understanding mechanisms of radiation damage in cells. The radius of the thermal core, Dd, at temperatures (or internal energy density) of up to 1,000 K, is observed to increase with LET, L, as Dd (in nanometers) = C4.L (in keV/microns)0.6, where, for example, C4 = 0.50 for T = 800 degrees C. PMID- 1641467 TI - Hit rates and radiation doses to nuclei of bone lining cells from alpha-particle emitting radionuclides. AB - Factors relating the local concentration of a bone-seeking alpha-particle emitter to the mean hit rate have been determined for nuclei of bone lining cells using a Monte Carlo procedure. Cell nuclei were approximated by oblate spheroids with dimensions and location taken from a previous histomorphometric study. The Monte Carlo simulation is applicable for planar and diffuse labels at plane or cylindrical bone surfaces. Additionally, the mean nuclear dose per hit, the dose mean per hit, the mean track segment length and its second moment, the percentage of stoppers, and the frequency distribution of the dose have been determined. Some basic features of the hit statistics for bone lining cells have been outlined, and the consequences of existing standards of radiation protection with regard to the hit frequency to cell nuclei are discussed. PMID- 1641468 TI - Determination of the acid dissociation constants for WR-1065 by proton NMR spectroscopy. AB - The acid dissociation constants for N-(2-mercaptoethyl)-1,3-diaminopropane (WR 1065) were determined in D2O by 360- and 500-MHz NMR spectroscopy. Results obtained at 0.21 M initial ionic strength and 26 degrees C were corrected to 25 degrees C yielding pKD1 = 8.28 +/- 0.04, pKD2 = 9.88 +/- 0.07, and pKD3 = 11.58 +/- 0.03. Correction of these values for the effect of the deuterium isotope upon the ionization reaction yielded dissociation constants in water of pKH1 = 7.69 +/ 0.09, pKH2 = 9.35 +/- 0.09, and pKH3 = 11.10 +/- 0.08. Analysis of the changes in chemical shift with pD indicated that the first ionization occurs largely through ionization of the thiol group (approximately 67%) and to a lesser extent the secondary ammonium group (approximately 30%), whereas the third ionization involves mainly the secondary ammonium group (approximately 65%) and to a lesser extent the primary ammonium group (approximately 30%). Estimates of the microscopic pK values for WR-1065 were also obtained from the results. PMID- 1641469 TI - Variations in pO2 and pH response to hyperthermia: dependence on transplant site and duration of treatment. AB - It has been clearly established that changes in intratumor pO2 and pH occur following hyperthermia, and it has been hypothesized that these changes may, in some way, be related to the ultimate response (i.e., cure) of the lesion. The purpose of this study was twofold: first, to examine the changes in intratumor pH during the course of a hyperthermia treatment at biologically related end point "doses"; second, to examine the response of pO2 after treatment in a different lesion transplant site. During hyperthermia treatment of the tumor transplanted in the leg, intratumor pH was found to drop from a control value of 6.74 +/- 0.17 to 6.47 +/- 0.13 within 15 min following the start of treatment. The values then remained relatively constant throughout the remainder of the treatment (either 1 or 2 h at 43.5 degrees C). Following the subcurative (10% tumor cures at 30 days; 60 min at 43.5 degrees C) treatment the pH began to rise immediately, while after the higher dose (60% tumor cures at 30 days; 120 min at 43.5 degrees C) a slight rise in pH was followed by a continuous drop in pH for up to 4 h, as we have reported previously. Oxygen response in the two transplant sites (leg and flank) was found to be remarkably different even though the tumor cure rate was identical for a given hyperthermia "dose" in terms of time and temperature. In the leg, only very low levels of oxygen can be measured in the tumor 24 h after treatment with either "dose" studied (all measured pO2 values less than or equal to 5 mm Hg). In the flank, the tumor response is dependent on hyperthermia "dose." Only 28% of measured oxygen values are less than or equal to 5 mm Hg 24 h following a subcurative "dose," while 4 h following the higher "dose" there is a nonsignificant trend toward hypoxia (approximately 65% of values less than or equal to 5 mm Hg) with a subsequent shift toward reoxygenation. These latter observations are contrary to results reported previously and tend to contradict some current theories regarding the physiological mechanisms associated with hyperthermia treatment. PMID- 1641470 TI - Nonlinear survival curves for cells of solid tumors after large doses of fast neutrons and gamma rays. AB - We have previously proposed that survival curves for cells of murine NFSa fibrosarcomas after exposure to fast neutrons might demonstrate curvature when the neutron doses reach a level high enough to cure the fibrosarcomas. We report here that this is the case. Murine NFSa fibrosarcomas growing in the hind legs of syngeneic mice were exposed to either gamma rays or fast neutrons. The tumors were removed and retransplanted into fresh recipients to obtain 50% tumor cell doses, from which the dose-cell survival relationship was constructed. Survival curves showed continuous bending down to 10(-7), and were well fitted using the linear-quadratic model. The alpha and beta values for neutrons were larger than those for gamma rays. When the surviving fractions at experimental TCD50 doses were calculated using these values, comparable figures were obtained for neutrons and gamma rays. The RBEs for neutrons were comparable for the TCD50 and TD50 assays. Neutron RBE was independent of dose within a range of 5-28 Gy. The capacity of the tumors to repair the damage caused by large doses of neutrons was identical to that for small doses of neutrons, indicating that cells retained the capacity to repair neutron damage irrespective of the size of the dose. PMID- 1641471 TI - Hypoxia and resistance to hydrogen peroxide confer resistance to tumor necrosis factor in murine L929 cells. AB - The mechanism whereby tumor necrosis factor (TNF) kills mammalian cells is not well understood, although oxidative damage has been suggested by several investigators. Further, it is not known why cells vary in their responsiveness to TNF. We show that the cytotoxic effect of TNF toward TNF-sensitive L929 cells is blocked under hypoxic conditions, suggesting a critical role of molecular oxygen and reactive oxygen species. To test whether cellular resistance to reactive oxygen species could provide resistance to TNF, we derived a variant strain from L929 cells by chronic exposure to an oxidizing agent, hydrogen peroxide (H2O2). These cells exhibit marked resistance to TNF as well as to H2O2. This cross protection provides additional evidence that mechanisms of resistance to oxidative damage are causally related to TNF-induced cell death. Scatchard analysis of TNF binding did not reveal significant differences between the H2O2 resistant line and the wild-type L929 line. On the other hand, analyses of antioxidant enzymes and glutathione levels in cells of the wild-type and the H2O2 resistant lines revealed several potentially important differences. Before exposure to TNF, the H2O2-resistant variants have elevated catalase activity, decreased activity of total glutathione-S-transferase (GST), and similar superoxide dismutase (SOD) activities. Exposure to TNF led to alteration in CuZnSOD activity, and much more so in the variants than in the wild-type L929 cells. However, no significant change in MnSOD activities in cells of either cell line was observed. Total GST activity was not altered appreciably by TNF in either cell line, but Western analysis showed that the level of alpha GST isozyme was increased and mu GST isozyme decreased in the H2O2-resistant variants. Furthermore, alterations in total glutathione content were observed in both the control and the variant cells. PMID- 1641472 TI - Analysis of radiation-induced micronuclei by fluorescence in situ hybridization (FISH) simultaneously using telomeric and centromeric DNA probes. AB - Fluorescence in situ hybridization using simultaneously a combination of DNA probes for the telomeric hexamer repeat (TTAGGG) and the centromerically repeated murine gamma-satellite DNA was applied to analyze the nature of radiation-induced micronuclei in mouse NIH 3T3 fibroblasts. After subtraction of spontaneously occurring micronuclei independent from the dose and time after irradiation, approximately 22% of the radiation-induced micronuclei did not reveal any hybridization signal. Approximately 17% showed one centromeric hybridization signal and about four telomeric signals, suggesting their origin from whole chromosomes. Almost 60% of radiation-induced micronuclei had telomeric signals only, suggesting their origin from acentric fragments. A fraction of micronuclei were found to contain two or more acentric fragments. Micronuclei derived from whole chromosomes or from multiple acentric fragments might, together with DNA synthesis in micronuclei, explain the occurrence of radiation-induced micronuclei with DNA contents greater than the largest chromosome arm. PMID- 1641473 TI - Induction by H2O2 of DNA and interphase chromosome damage in plateau-phase Chinese hamster ovary cells. AB - The induction by H2O2 of DNA breaks, DNA double-strand breaks (DSBs), and interphase chromatin damage and their relationship to cytotoxicity were studied in plateau-phase Chinese hamster ovary (CHO) cells. Damage in interphase chromatin was assayed by means of premature chromosome condensation (PCC); DNA DSBs were assayed by nondenaturing filter elution (pH 9.6), and DNA breaks by hydroxyapatite chromatography. Cells were treated with H2O2 in suspension at 0 degrees C for 30 min and treatment was terminated by the addition of catalase. Concentrations of H2O2 lower than 1 mM were not cytotoxic, whereas concentrations of 40 and 60 mM reduced cell survival to 0.1 and 0.004, respectively. An induction of DNA breaks that was dependent on H2O2 concentration was observed at low H2O2 concentrations that reached a maximum at approximately 1 mM; at higher H2O2 concentrations induction of DNA breaks either remained unchanged or decreased. Damage at the chromosome level was not evenly distributed among the cells, when compared to that expected based on a Poisson distribution. Three categories of cells were identified after exposure to H2O2: cells with intact, control-like chromosomes, cells showing chromosome fragmentation similar to that observed in cells exposed to ionizing radiation, and cells showing a loss in the ability of their chromatin to condense into chromosomes under the PCC reaction. The fraction of cells with fragmented chromosomes, as well as the number of excess chromosomes per cell, showed a dose response similar to that of DNA DSBs, reaching a maximum at 1 mM and decreasing at higher concentrations. The results indicate that induction of DNA and chromosome damage by H2O2 follows a complex dependence probably resulting from a depletion of reducing equivalents in the vicinity of the DNA. Reducing equivalents are required to recycle the transition metal ions that are needed to maintain a Fenton-type reaction. The absence of cell killing at H2O2 concentrations that yielded the maximum amount of DNA and chromosome damage suggests that this damage is nonlethal and repairable. It is suggested that lethal DNA and chromosome damage is induced at higher concentrations of H2O2 where cell killing is observed by an unidentified mechanism. PMID- 1641474 TI - Reduction of levels of nuclear-associated protein in heated cells by cycloheximide, D2O, and thermotolerance. AB - Hyperthermia increases levels of nuclear-associated proteins in a manner that correlates with cell killing. If the increase in nuclear-associated proteins represents a lethal lesion then treatments that protect against killing by heat should reduce and/or facilitate the recovery of levels of the proteins in heated cells. This hypothesis was tested using three heat protection treatments: cycloheximide, D2O, and thermotolerance. All three treatments reduced levels of the proteins measured immediately following hyperthermia at 43.0 or 45.5 degrees C, with the greatest reduction occurring at 43.0 degrees C. In addition to reducing the proteins, thermotolerance facilitated the recovery of the proteins to control levels following hyperthermia. Thus thermotolerance may protect cells by both reducing the initial heat damage and facilitating recovery from that damage. Cycloheximide and D2O did not facilitate recovery of nuclear-associated proteins, suggesting that their protection against cytotoxicity related to the proteins resulted solely from their reduction of increases in levels of the proteins. All three treatments have been shown to stabilize cellular proteins against thermal denaturation. The results of this study suggest that the increase in nuclear-associated proteins may result from thermally denatured proteins adhering to the nucleus and that it is the ability of cycloheximide, D2O, and thermotolerance to thermostabilize proteins that reduces the increase in levels of the proteins within heated cells. PMID- 1641475 TI - The contribution of DNA and chromosome repair deficiencies to the radiosensitivity of ataxia-telangiectasia. AB - Cells derived from individuals with ataxia-telangiectasia (AT) are more sensitive to ionizing radiation and radiomimetic drugs, as evidenced by decreased survival and increased chromosome aberrations at mitosis when compared with normal cell lines. Our previous studies showed that, despite similar initial levels of DNA double-strand breaks (DSBs), AT cells express higher initial chromosome damage than do normal cells as demonstrated by the technique of premature chromosome condensation. However, this finding accounted for only a portion of the increased sensitivity (T. K. Pandita and W. N. Hittelman, Radiat. Res. 130, 94-103, 1992). The purpose of the study reported here was to examine the contribution of DNA and chromosome repair to the radiosensitivity of AT cells. Exponentially growing AT and normal lymphoblastoid cells were fractionated into cell cycle phase-enriched populations by centrifugal elutriation, and their DNA and chromosome repair characteristics were evaluated by DNA neutral filter elution (for DNA DSBs) and by premature chromosome condensation, respectively. AT cells exhibited a reduced fast-repair component in both G1- and G2-phase cells, as observed at the level of both DNA DSBs and the chromosome; however, S-phase cells showed nearly normal DNA DSB repair. The findings that AT cells exhibit an increased level of chromosome damage and a deficiency in the fast component (but not the slow component) of repair suggest that chromatin organization might play a major role in the observed sensitivity of AT cells. When survival was plotted as a function of the residual amount of chromosome damage in G1- and G2- phase cells after 90 min of repair, the curves for normal and AT cells approached each other but did not overlap. These results suggest that, although higher initial levels of chromosome damage and reduced chromosome repair capability can explain much of the radiosensitivity of AT cells, other differences in AT cells must also contribute to their sensitivity phenotype. PMID- 1641476 TI - Point mutations, deletions, and radiation carcinogenesis. PMID- 1641477 TI - The radiography essentials: an evolutionary perspective. AB - A review of all the Radiography Essentials since their inception in 1944 provides an insightful look into the history and dynamics of entry-level educational standards in radiography. As successive Essentials have been revised, more attention has been given to the clinical environment, a broadened and strengthened curricula and due process. Additionally, radiographers have gained greater autonomy in delivering professional entry-level education in radiography. PMID- 1641478 TI - Factors affecting student program and career selection. AB - This study uses a national sample of freshman radiography students to examine demographic data and factors that affected career and program choice. The data are discussed in terms of implications for marketing and recruitment strategies. PMID- 1641479 TI - An overview of methods in stereotactic radiosurgery. AB - Stereotactic radiosurgery delivers a single high dose of ionizing radiation to a radiographically well-defined, small intracranial target without delivering a significant proportion of the prescribed dose to the surrounding brain tissue. Three methods of delivering the radiosurgical technique include the gamma knife, heavy charged particle beams and external high-energy photon beams from linear accelerators. PMID- 1641480 TI - Evolution of a degree program: the Australian example. AB - The progression of undergraduate radiography programs from diploma to bachelor's degree level has become a reality in Australia. This article outlines the evolution, underlying philosophy and structure of the bachelor of applied science in medical radiations program conducted by the Department of Medical Radiations Science at the Royal Melbourne Institute of Technology. PMID- 1641481 TI - Organ donation: a crisis with a cure. PMID- 1641482 TI - Evaluation of the high-risk patient. PMID- 1641483 TI - [Development and future perspectives of PET technology]. AB - The physical principle of PET is discussed, and its advantages compared with SPECT are presented. Starting from the status of PET today, future developments are discussed with special reference to three-dimensional acquisition and reconstruction. PMID- 1641484 TI - [The integration of positron emission tomography into noninvasive cardiovascular diagnosis]. AB - Cardiac positron emission tomography is a noninvasive imaging modality that can be used to assess regional myocardial blood flow and metabolism. This combined noninvasive approach to the evaluation of acute or chronic injury to the myocardium is superior to all other imaging modalities. With increasingly widespread use of positron emission tomography it is becoming evident that patients with impaired left ventricular ejection fraction (less than or equal to 35%) resulting from congestive heart failure and patients soon (72-96 h) after acute myocardial infarction in particular may benefit from definition of metabolically active myocardium to stratify therapeutic assessment. PMID- 1641485 TI - [Preoperative localization diagnosis in focal epilepsy using PET]. AB - We present results of studies in which positron emission tomography was applied to the presurgical evaluation of epileptics. Emphasis is placed on results of PET studies with various tracers in partial epilepsies and on the use of PET in age related epileptic syndromes in children. PMID- 1641486 TI - [Positron emission tomography of the thorax. The current clinical status]. AB - The non-invasive diagnostic assessment of thoracic lesions has been greatly enhanced by the use of positron emission tomography with metabolic active radio compounds such as fluor-18 labeled deoxyglucose. Four clinical fields of use were established: differential diagnostic evaluation of lesions (T-staging); classification of adenopathy (N-staging); therapy response monitoring; diagnostic evaluation of recurrence. The upcoming challenges for clinical use are limited availability and necessary technical and qualitative standardizations. PMID- 1641487 TI - [Positron emission tomography (PET) in the evaluation of tumor proliferation and follow-up of therapy in ear, nose and throat tumors]. AB - The uptake of 18F-Deoxyglucose (FDG) was studied in vivo in patients with head and neck tumors with positron emission tomography (PET) in relation to the proliferation rate of these tumors. The quantitative analysis of the radioactivity concentrations revealed two groups, showing a high or a lower FDG uptake pattern. In both groups the FDG uptake and the proliferation rate were correlated with a flat slope of the regression function. It is suggested that these differences in uptake in histologically identical tumor populations may correspond to differences at the molecular level, e.g. differences in the amount of the glucose carrier, perhaps caused by activated oncogenes. Furthermore PET was applied to evaluate therapeutic effects in patients with advanced head and neck cancer. We found that multiple lymph node metastases in the same patient can show a different baseline metabolism and also different changes following therapy. Tumors were more sensitive to therapy than lymph node metastases. The growth rate and the change in FDG uptake were highly correlated with different regression functions for tumors and lymph node metastases. These data demonstrate that PET with FDG can be used to assess early chemotherapeutic effects. The information gained with PET can be included in the treatment planning in patients undergoing systemic chemotherapy. PMID- 1641488 TI - [Hemangioma of the left ventricle]. AB - The authors describe the case of a histologically proven hemangioma in the left coronary artery of the left ventricle of a 24-year-old woman. The results of the different medical imaging methods applied are described and the treatment of cardiac angiomas is discussed. PMID- 1641489 TI - [A retroperitoneal space-occupying lesion following tumor nephrectomy]. PMID- 1641490 TI - The treatment and management of neuroleptic malignant syndrome. AB - 1. The neuroleptic malignant syndrome was initially described as a disorder specifically related to neuroleptic usage with frequent fatal outcome. The observations of variant or mild cases of this syndrome as well as case reports on neuroleptic-malignant-like syndromes in the absence of neuroleptics raises the issue of the usefulness of this terminology and highlights the potential for inappropriate management of this "malignant" syndrome. It has been suggested that hypothalamic thermoregulatory responses may involve an interplay among noradrenergic, cholinergic and serotonergic pathways. Out treatment strategy is based on the pharmacology of neuroleptics and empirical data, verified in our own clinical practice and considers that it is often difficult to determine whether certain physiologic states are a consequence to or specific triggering factors. 2. If a patient's temperature is less than 101, we emphasize vigorous treatment with anticholinergic agents, while simultaneously assessing the psychiatric need for neuroleptics versus medical risks. Given that the severe rigidity of NMS represents severe extrapyramidal effects of dopamine blockade, there is no reason to withhold anticholinergics in the absence of higher temperatures. Neuroleptics can be stopped at the discretion of the clinician even during circumstances when there is fever below 101. 3. In cases of severe EPS with fever greater than or equal to 101, we recommend stopping neuroleptics, treating with anticholinergics and starting with dopamine agonists. In the event of a poor response to dopamine agonists, a brief trial of dantrolene and/or benzodiazepines is recommended. Dantrolene should not be introduced for prolonged periods, since abnormal liver function studies have been observed in approximately 1.8% of patients. 4. In cases of extreme hyperpyrexia (fever greater than 103), clinicians should consider transfer to an ICU or another medical support. Extreme temperatures have been associated with potentially irreversible cerebellar or other brain damage, if not aggressively treated. If neuroleptics are later indicated, a 2 week interval after resolution of symptoms should be maintained before reinstituting neuroleptics. 5. In patients with severe EPS without fever, we emphasize aggressive use of anticholinergic therapy, while simultaneously considering the psychiatric need for neuroleptics versus medical risks. In all cases where a patient's swallowing, respirations or physical mobility is severely compromised, we suggest stopping neuroleptics. Anticholinergic agents should be continued for 7 days after neuroleptics are stopped. If anticholinergic agents are unsuccessful after 2-3 dosages, dopamine agonists may be added, while simultaneously monitoring vital signs. It should be emphasized that severe EPS sometimes takes days to improve even after neuroleptic cessation and the addition of anticholinergics.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1641491 TI - MRI-SPECT and PET-EEG findings on brain dysfunction in schizophrenia. AB - 1. In this article the author reviews a series of investigations on brain dysfunction in untreated schizophrenics using manumotor and music listening tasks as activation paradigms. Methods involved were EEG mapping, Single Photon Emission Computerized Tomography (SPECT; Xenon-133 inhalation method), Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET; 11-2-Deoxyglucose as tracer). 2. Major signs of brain dysfunction yielded a "nonreactivity" on both motor and music stimulation in patients displaying marked negative symptomatology, as shown consistently by EEG Mapping, SPECT and PET. In contrast, first-break patients with predominant "positive" and without underlying negative symptoms showed signs of "normal" to "diffuse hyperactivation" on such stimulations, as demonstrated by EEG and SPECT imaging methods. 3. Interestingly, MRI planimetry of the size of the corpus callosum (CC) corroborated the above findings, showing a significantly larger CC in "positive" than "negative" patients. 4. Together with functional imaging findings of other working groups and recent neuropathological theories we finally raise some speculative neurophysiological hypotheses on brain dysfunction in subgroups of schizophrenics, which might have direct implications for treatment and follow-up of these patients. PMID- 1641492 TI - Effects of tobacco smoking on the topographic EEG II. AB - 1. Tobacco smokers are well aware of the long term hazards of tobacco smoking, yet they continue to smoke. Presumably people smoke because of short term gains due to nicotine. 2. The mechanism by which nicotine is a drug reinforcer still needs a great deal of study. The specific aim of the present study was to determine the effects of tobacco smoking on the topographic EEG of 12 hr deprived heavy tobacco smokers. 3. Seven normal adult tobacco smokers of mixed sex were recruited into the study and compared with six normal nonsmokers of similar age and sex. 4. A Grass Model 8-24D EEG and 16 different scalp monopolar electrodes were used to record the EEG using both ears as reference before and after smoking. EKG lead II was recorded on channel 17. Blood pressure was measured by auscultation. Exhaled CO was measured using a CO detector. Computer analysis of the EEG data was run of line on a Zenith 386/25 microcomputer using RHYTHM 7.1. The same system was used to store the EEG in digitized form. The maximum number of 4 sec artifact free epochs in a 3 min recording period with eyes open and then closed was used before and after low and high nicotine tobacco or sham smoking. 5. The hypothesis of this research was confirmed, i.e., that tobacco smoking of high nicotine cigarettes (about 2.0 mg/cigarette) would cause a shift in EEG alpha rhythm to higher frequencies in more diffuse midline cortical structures. In other studies an increase in alpha rhythm has been correlated with an awake relaxed behavioral state. 6. A heart rate increase was a more sensitive index of tobacco smoking than an increase in arterial blood pressure. Exhaled smoking CO levels correlated with the nicotine and tar content of the cigarette. PMID- 1641493 TI - The treatment of affective disorder with carbamazepine: prophylactic synergism of lithium and carbamazepine combination. AB - 1. In order to examine the prophylactic interaction between lithium and carbamazepine (CBZ), 18 patients who had been treated prophylactically with a combination of lithium and CBZ (combination therapy), lithium alone (Li-therapy), or CBZ alone (CBZ-therapy) were investigated in terms of episode occurrence. 2. The results revealed that the duration of symptoms and the frequency of hospitalization per year were significantly lower in the combination therapy than in both the Li-therapy and the CBZ-therapy. 3. In 7 out of 18 patients, the best prophylactic effect was obtained during combination therapy and none of the parameters measured was definitely inferior to those measured during the two single therapies. 4. During combination therapy, serum lithium level was significantly lower than during Li-therapy in the CBZ responders, and the combination of the two drugs enabled the required concentrations of lithium to be decreased. 5. It was concluded that synergistic action and a decrease in required concentrations of lithium can be expected with the combined use of lithium and CBZ, especially in responders to CBZ. PMID- 1641494 TI - Thyrotropin responses to TRH and MHPG excretion before and after an electroconvulsive therapeutic course in depressed patients. AB - 1. TSH response to TRH, and urinary MHPG were investigated before and after an ECT course in 12 female patients with endogenous depression. 2. The changes caused by ECT treatment on these parameters were not significant. 3. A positive correlation (r = 0.75, p = 0.005) was found between the changes in TSH response and the changes in urinary MHPG excretion. PMID- 1641495 TI - Effects of mianserin in chronic schizophrenia. AB - 1. The efficacy of mianserin as a supplement in treating chronic schizophrenia was tested by monitoring the BPRS and plasma monoamine metabolites. 2. Twenty inpatients with schizophrenia were administered fixed doses of neuroleptics throughout the study. 3. A control BPRS scoring and blood sampling were done before mianserin administration. 4. Fixed doses of 60 mg/day of mianserin for 2 weeks and flexible doses for 4 weeks were given orally in an open study for 6 consecutive weeks, and no treatment followed for 1 additional week. 5. BPRS scoring was carried out once weekly, and blood samples were obtained after mianserin treatment. 6. Both total BPRS scores and scores for negative symptoms were decreased by mianserin treatment as compared with the control values. 7. 5 HIAA concentrations of both responding patients and nonresponding patients to mianserin were increased after medication; however, 5-HIAA values of responding patients were lower than those of nonresponding patients. 8. HVA concentrations of the responding group were slightly increased by mianserin administration. 9. There were no significant changes in MHPG levels between the two groups. 10. These results suggest that the negative symptoms of schizophrenia are partly improved by mianserin treatment. PMID- 1641496 TI - Daily activity and persistent sleep-wake schedule disorders. AB - 1. Patients with disorders of entrainment to external time cues such as delayed sleep phase syndrome (DSPS) and non-24-hour sleep-wake syndrome (HNS) were treated with non-pharmacological interventions and/or pharmacological agents. 2. Resetting the circadian clock with chronotherapy was easy in all DSPS patients, but it was not as easy to maintain the reset rhythm without additional therapy. Triazolam was effective in treating the phase delay that reappeared after chronotherapy. 3. Vitamin B12 (methylcobalamin) was strikingly effective in some patients with DSPS or HNS. 4. All the adolescent patients who complained of inability to attend school finally returned to their classes after treatment. Maintaining the reset rhythm in adolescent patients was easier than in adults. PMID- 1641497 TI - Adjunctive imipramine for dysphoric schizophrenic patients with past histories of cannabis abuse. AB - 1. Twenty-one schizophrenic or schizoaffective patients with histories of cannabis abuse and operationally-defined syndromes of post-psychotic depression completed a double-blind trial of adjunctive imipramine added to their on-going medication regimen of fluphenazine decanoate and benztropine. 2. The imipramine treated patients had superior global outcome. 3. Subscales suggested that specific improvement occurred in imipramine-treated patients in the domain of depression-like features. 4. Psychotic symptomatology was not found to be exacerbated by the imipramine. PMID- 1641498 TI - Differential behavioral response in LEW/N and F344/N rats: effects of corticotropin releasing hormone. AB - 1. Previous studies have documented that LEW/N rats exhibit an inflammatory response when challenged with a variety of stressful stimuli while histocompatible F344/N rats do not. These differences are thought to be regulated by the HPA axis. 2. In order to examine behavioral correlates of suspected differences in HPA activity in these strains, the baseline response to an open field as well as the effects of 3 micrograms/rat of CRH i.c.v. were compared across strains. 3. Significant differences in the pattern of activity in the open field, rearing, and grooming, as well as effects of CRH were found between strains. 4. The differences found are consistent with the notion that differences in endogenous CRH may form the basis for the differential susceptibility of these strains to autoimmune disease, and provide a model to study genetic determinants of CNS-immune system interactions. PMID- 1641499 TI - Postnatal development of regional binding of corticotropin-releasing factor and adenylate cyclase activity in the rat brain. AB - 1. Corticotropin-releasing factor (CRF) plays a major role in the endocrine, autonomic and behavioral responses to stress. The distribution of CRF and CRF receptors in hypothalamic and extra-hypothalamic brain regions is consistent with its stress-related functions. 2. In most brain regions, CRF acts primarily, if not exclusively, through activation of the adenylate cyclase systems. 3. While previous studies have demonstrated the prenatal presence of CRF receptors, in the early postnatal period the abundance of CRF receptors relative to the magnitude of CRF-stimulated cAMP production suggests that CRF receptors are not fully linked to adenylate cyclase. 4. Because of our interest in the possible involvement of CRF signal transduction in the development of the neonatal stress response, we have examined postnatal development of CRF receptors in relation to adenylate cyclase activity in the rat. 5. CRF binding decreased significantly in the hippocampus and striatum from postnatal days 7-21. Basal adenylate cyclase activity peaked in the second-third week of postnatal life in each brain region. Preliminary studies suggest that early stress can alter the maturation of second messenger systems in the frontal cortex. PMID- 1641500 TI - Role of oxygen-derived free radicals on rat splanchnic eicosanoid production during acute hemorrhage. AB - The effect of superoxide dismutase (SOD), an oxygen-derived free radical scavenger, on rat splanchnic eicosanoid synthesis was examined following hemorrhagic shock. Anesthetized male rats were hemorrhaged to 30 mm Hg for 30 minutes (Shock), killed, or treated with the shed blood (Shock plus reperfusion). The Shock plus reperfusion group was treated with saline vehicle or SOD (2500, 5000, 7500, 10,000 or 15,000 U/Kg, i.v.) 15 minutes prior to the reperfusion of the shed blood. The superior mesenteric artery was removed in continuity with the end organ intestine (SV+SI) and perfused in vitro with oxygenated Krebs-Henseleit buffer (3 ml/min at 37 degrees C). Venous effluent was measured for basal release of 6-keto-PGF1 alpha, PGE2 and thromboxane B2 at 15, 30, 60 and 90 minutes of perfusion. The SV+SI compensated for acute shock by increased release of 6-keto PGF1 alpha (300%) (and not PGE2 or thromboxane B2) which was abolished by reperfusion of the shed blood following shock. Prior treatment of the Shock plus reperfusion group with 7500 U/Kg or more of SOD restored the increased release of SV+SI 6-keto-PGF1 alpha found following shock alone (p less than 0.05). These data provided indirect evidence that ODFRs contributed to endogenous SV+SI regulation of PGI2 synthesis and release during hemorrhagic shock and reperfusion of shed blood. PMID- 1641501 TI - Ovarian and uterine prostaglandin E2-9-ketoreductase activity in cyclic and pregnant ewes. AB - The regulation of luteal function in sheep appears to be dependent in part upon relative utero-ovarian concentrations of PGE2 and PGF2 alpha. Prostaglandin E2-9 ketoreductase converts PGE2 (a putative antiluteolysin) to PGF2 alpha. Enzymatic activity was measured in a cytosolic subcellular fraction of luteal and endometrial tissues collected on days 10, 13 and 16 of the estrous cycle or pregnancy. Respective days represented times before, during, and after the critical period for maternal recognition of pregnancy. Preparations of enzyme were incubated in the presence of tritiated PGE2. Radiolabeled PGF2 alpha (ie., product) was separated from PGE2 by gel filtration chromatography and quantified by liquid scintillation spectrometry. There were no significant differences due to time of tissue collection or pregnancy status in enzymatic activity of luteal tissues. Prostaglandin E2-9-ketoreductase activity isolated from endometria of open ewes was greater than their pregnant counterparts on days 13 and 16. Thus, the potential capacity of the ovine uterus to generate luteolytic PGF2 alpha from PGE2 substrate is elevated during an infertile estrous cycle. PMID- 1641502 TI - Interleukin-1 beta stimulates decidual stromal cell cyclo-oxygenase enzyme and prostaglandin production. AB - The cytokine interleukin-1 (IL-1 beta) increased prostaglandin production by decidual stromal cells in culture in a time and dose dependent manner. Optimum conditions for stimulation were found to be for 24 hours at a concentration of 100 pg IL-1 beta/ml. An apparent increase in cyclo-oxygenase enzyme synthesis accompanied the increase in prostaglandin production, and both changes were inhibited by the protein synthesis inhibitor cycloheximide. This implicates protein synthesis in the stimulatory effects of IL-1 beta, which may be mediated through the increase in cyclo-oxygenase enzyme. A pre-incubation period of 72 hours was found to be necessary to observe the stimulatory effect of IL-1 beta on prostaglandin production, but this did not seem to be due to any change in the sensitivity of the cells to IL-1 beta; the increase in the number of cyclo oxygenase positive cells was the same if IL-1 beta was added on day 1, day 2 or day 3 of culture, even though prostaglandin production was not stimulated on day 1 or day 2. Cycloheximide increased prostaglandin production on the first two days of culture and had no effect on the third day of culture. This was interpreted as indicating that a factor inhibiting cyclo-oxygenase activity was synthesised during the initial period of culture, which prevented any increase in prostaglandin production following the increase in enzyme synthesis. PMID- 1641503 TI - NADP-dependent 15-hydroxyprostaglandin dehydrogenase is homologous to NAD dependent 15-hydroxyprostaglandin dehydrogenase and other short-chain alcohol dehydrogenases. AB - Human tissues contain two enzymes that catalyze the oxidation of the 15-hydroxy group of prostaglandins: NAD-dependent 15-hydroxyprostaglandin dehydrogenase which is fairly specific for prostaglandins and NADP-dependent 15 hydroxyprostaglandin dehydrogenase with low specificity for prostaglandins. The recent determination of the amino acid sequence of the NAD-dependent enzyme has revealed similarities with a number of oxidoreductases with distinct specificities that constitute the short-chain alcohol dehydrogenase family. Comparison of the amino acid sequence of NADP-dependent 15-hydroxyprostaglandin dehydrogenase with the sequences of the NAD-dependent enzyme and other short chain alcohol dehydrogenases revealed the same similarities, identifying the NADP dependent enzyme as a short-chain alcohol dehydrogenase. The degree of homology between the two 15-hydroxyprostaglandin dehydrogenases is similar to the one between each of the two enzymes and other members of the family indicating an early evolutionary divergence of the two proteins. PMID- 1641504 TI - A retrospective study of 932 second trimester terminations using gemeprost (16,16 dimethyl-trans delta 2 PGE1 methyl ester). AB - A retrospective study of 932 second trimester terminations between 12-27 weeks gestation was carried out to determine the efficacy of gemeprost for second trimester termination. A single course of 5 x 1 mg gemeprost pessaries was administered every three hours. If abortion had not occurred after the first course of pessaries, a further course of 5 x 1 mg pessaries was administered. Intravenous oxytocin was administered after 36 hours if abortion had not occurred. Eighty per cent and ninety five per cent of patients aborted within 24 and 48 hours respectively. Of the remaining 5 per cent of women, 3 per cent aborted with escalating doses of oxytocin. In the remaining 18 (2 per cent) women, the pregnancies were electively terminated with an alternative method. The median induction-abortion interval was 18.0 hours and 15.0 hours in nulliparous and parous women respectively (P less than 0.0001). The number of pessaries required to induce abortion was not influenced by parity. Significantly more parous women bled more than 500 ml. The incidence of pelvic sepsis (0.1 per cent) and cervical tear (0.1 per cent) was low. Twenty six per cent of women had diarrhoea and 23 per cent vomited following administration of prostaglandin. This study confirmed the efficacy of gemeprost for second trimester termination of pregnancy. This method of termination is safe, non-invasive, simple and has a low complication rate. PMID- 1641505 TI - Eicosanoid synthesis and Helicobacter pylori associated gastritis: increase in leukotriene C4 generation associated with H. pylori colonization. AB - The importance of pro-inflammatory leukotriene C4 in Helicobacter pylori (H. pylori) associated gastritis in man is unknown. Fresh gastric biopsy specimens from 28 dyspeptic patients were obtained: 10 showed normal antral histology with no evidence of H. pylori, the remaining 18 patients exhibited histological gastritis and were H. pylori positive as assessed by histology, culture and urease test. Twelve of these 18 patients received 240 mg twice daily colloidal bismuth subcitrate for four weeks before re-endoscopy. Gastric biopsies from H. pylori positive patients were incubated under basal and Ca(2+)-ionophore mediated conditions: Radioimmunoassay analysis of the supernatant showed basal release of prostaglandin E2 and leukotriene C4 was slightly but not significantly elevated in H. pylori positive mucosa. However in H. pylori positive mucosa there was an 85% increase in leukotriene C4 synthesis when biopsies were incubated with ionophore, compared to only 13% increase in H. pylori negative mucosa (p less than 0.02). After eradication of H. pylori by colloidal bismuth subcitrate, there was a clearance of inflammatory cell infiltrate as assessed by histology and a significant reduction in ionophore-mediated leukotriene C4 formation compared with before treatment (p less than 0.02). These results suggest that H. pylori gastritis is associated with increased capacity to generate leukotriene C4, which may amplify the damaging effects of the bacteria on gastric mucosa. PMID- 1641506 TI - [Inability to mourn. Does the diagnosis hold up against an evaluation? On psychological processing of the Holocaust in Germany]. AB - The book The Inability to Mourn by Alexander and Margarete Mitscherlich appeared in 1967 and claimed to provide a diagnosis of the era in which it was written. Superficially at least, its public impact was considerable. Rereading the work 25 years later, Tilmann Moser has profound misgivings as to the accuracy of the Mitscherlichs' diagnosis. He characterises the authors' approach as a mixture of analytic-cum-therapeutic, political and pedagogical attitudes and suggests that this was largely inappropriate to the task of identifying the actual psychic condition of the "generation of culprits" and of encouraging self-recognition and a disposition for change. Moser posits the "tragic paradox" that the people implicated in this crime require empathy if they are to genuinely break with the past. PMID- 1641507 TI - [The (in)ability to mourn in East and West Germany. What mourning could mean]. AB - Together, the fall of the Berlin Wall, the reunification of Germany and the public reactions to the war in the Gulf form a syndrome that poses anew the question of the specifically German "ability to mourn". On the one hand, the author registers a continuing rejection of the onerous task of facing up to the reality of the past via recollection and mourning. On the other, she sees indications both on the individual and collective level that this rejection is beginning to crumble, thus encouraging the emergence of attitudes that challenge the validity of German "ideals" to an increasing extent. PMID- 1641508 TI - [German unification influenced by an unfinished psychosocial history]. AB - The critical form of social psychology presented here is concerned with the modalities and results of German reunification. It proceeds from Freud's insistence on the functional autonomy of psychic dispositions and unconscious forms of identification vis-a-vis the political and economic spheres. With reference to earlier historical experience of the Germans as an "economic nation" the authors suspect that German reunification with the avowed "economistic" priority of establishing the same life conditions in East and West is once again suppressing those problems that are bound up with the post-fascist syndrome handed down from one generation to the next. With a view to casting light on the reunification process and the collective psychic potentials it has released, the authors supplement Freud's mass-psychology approach with Julia Kristeva's outline of a social psychology that hinges on the relationship between cosmopolitanism and the national idea. PMID- 1641509 TI - Interrelationships between protein phosphorylation and oligomerization in transport and chemotaxis via the Escherichia coli mannitol phosphotransferase system. AB - The membrane-bound enzymes II of the bacterial carbohydrate phosphotransferase system (PTS) are multifunctional: they are required for the transport, phosphorylation and chemotactic sensing of their substrates. An oligomer (minimally a dimer) of at least one of these PTS permeases, the Escherichia coli mannitol permease, appears to be necessary for this protein to optimally carry out these functions. Much indirect evidence is consistent with this hypothesis, and recent experiments show that transport and phosphorylation of, and chemotaxis to, mannitol in E. coli involves an intersubunit phosphotransfer reaction, which can only occur in a protein oligomer. Membrane topological studies of the mannitol permease also argue in favour of an oligomeric structure in the membrane which may be necessary to form the hydrophilic channel through which mannitol must traverse the phospholipid bilayer. The possibility that the oligomerization state of the mannitol permease is a target for regulation of its activity in vivo is proposed, but has not yet been explored experimentally. PMID- 1641510 TI - Identification of a lacZ gene in Vibrio cholerae. AB - Plasmids that express an enzymatically active beta-galactosidase in an Escherichia coli delta lac strain were isolated from libraries of recombinant plasmids containing Vibrio cholerae chromosomal DNA. Deletion analysis localized the gene responsible for beta-galactosidase activity on a 3.1-kb DNA fragment, and the gene product was identified as a protein of approximately 110 kDa. Primary sequence comparisons indicated that this V. cholerae gene is homologous to the E. coli lacZ gene. In contrast to the lac loci of other bacteria, no gene that could specify a lactose transport system was detected in the vicinity of the V. cholerae lacZ gene, which may account for the inability of this species to use lactose. In V. cholerae, portions of open reading frames encoding proteins homologous to the Alcaligenes eutrophus chrA and E. coli galR gene products were detected upstream and downstream from the lacZ gene, respectively. PMID- 1641511 TI - Detection of intraspecific DNA polymorphism in Streptococcus salivarius subsp. thermophilus by a homologous rDNA probe. AB - Three ribosomal probes from Streptococcus salivarius subsp. thermophilus were cloned. Sequence data demonstrate that their juxtaposition corresponds to an entire operon. They were used in order to study ribosomal operon number and organization. rRNA genes were shown to be clustered in the order 5'-16S-23S-5S-3' and the number of rrn loci to vary within the subspecies. The smallest of the 3 probes was used for strain characterization. Substantial variability in hybridization patterns was observed among strains, resulting not only from, restriction fragment length polymorphism (RFLP) but also from the variability of ribosomal operon number. PMID- 1641512 TI - N-unsubstituted glucosamine residues and other modifications in murein of the obligatory chemolithotroph Thiobacillus neapolitanus. AB - Purified murein from Thiobacillus neapolitanus was poorly digested by lysozyme. It's sensitivity to the enzyme greatly increased after N-acetylation. The murein was found to contain 30 to 35% glucosamine residues lacking N-acetyl groups. It also contained phosphomuramic acid. Further modifications included amidation of diaminopimelic acid in the peptide side chains and a low alanine content. None of these modifications were found in the murein of another sulphur bacterium, Thiobacillus versutus. PMID- 1641513 TI - Molecular typing of Brucella with cloned DNA probes. AB - Brucella constitutes a single genomic species (B. melitensis); however, for epidemiological studies, methods are needed for discriminating strains within this genomic species. DNA samples from 112 Brucella strains were cleaved by restriction endonucleases and the fragments separated by agarose gel electrophoresis and transferred to nylon membranes. When the DNA fragments on the membranes were probed with 32P-labelled 16 + 23 S rRNA from Escherichia coli, a single rRNA gene restriction pattern was obtained after cleavage with all endonucleases tested (HindIII, EcoRI, SmaI, and XhoI) except BamHI. This indicated high genomic homogeneity within the single Brucella species. Of 30 probes consisting of random Brucella DNA fragments cloned into lambda EMBL3, 20 yielded a single BamHI restriction pattern per probe when applied to 112 Brucella DNA tested. However, 7 probes yielded 3 to 12 different patterns among DNA tested. These patterns more-or-less correlated with the classification of strains into biogroups (Melitensis, Abortus, Suis, Neotomae, Ovis and Canis) and biovars (18 biovars represented). Probe A was capable of separating biogroup Melitensis from the other biogroups. Probe C separated the set of biogroups Melitensis Abortus-Ovis from the other biogroups. By reference to the patterns obtained using 1 to 7 probes, the most frequently occurring biovars (Melitensis 1, Melitensis 3, Abortus 1, Abortus 3, Suis 2 and Ovis) could be distinguished from each other. Eight biovars showed more than one pattern with 1 to 7 probes. The proposed typing system should be useful for epidemiological subtyping and does not pose safety problems once the DNA has been extracted. PMID- 1641514 TI - Mycobacterium paratuberculosis binds fibronectin. AB - Fibronectin, an adhesive glycoprotein which is present in plasma and on many host cell surfaces of many host organisms, binds to certain bacterial pathogens. This study demonstrates the ability of Mycobacterium paratuberculosis (M.ptb) to interact with 125I-labelled fibronectin purified from bovine and ovine plasma. Two M.ptb strains were tested: a clinical isolate and a commercially available vaccine strain. Both strains showed significant fibronectin-binding activities of 22 and 41%, respectively, whereas non-pathogenic M.phlei had almost no affinity for fibronectin. Binding activities were similar for ovine and bovine fibronectin. We found that fibronectin binding by M.ptb was (1) time-dependent, reaching saturation within 90 min, (2) specific, since it was inhibited by an excess of unlabelled fibronectin but not by albumin, (3) saturable, with an apparent dissociation constant of 1.25 x 10(-9) M and a maximal number of 1,600 binding sites per bacterium, and (4) sensitive to detergents, proteases and heat treatments, indicating the protein nature of the responsible binding component(s). Scatchard plot analysis gave a straight line suggesting the presence of a single type of fibronectin receptor on M.ptb. PMID- 1641515 TI - [Isolation and characterization of a flocculating mutant of Saccharomyces diastaticus]. AB - A flocculating strain of Saccharomyces diastaticus NRRL2416 was isolated after ethidium bromide mutagenesis and density gradient separation. Flocculation did not change the general characteristics of the strain. Flocculation was better on maltodextrin-containing media than on others. It was found to be calcium dependent and sensitive to growth conditions. The deflocculating effects of some sugars suggested that mannose may be involved in the mechanism of flocculation, as for strains of the FLO1 phenotypic group. PMID- 1641517 TI - Amplification of a particular DNA sequence in Streptomyces ambofaciens RP181110 reversibly prevents spiramycin production. AB - Streptomyces ambofaciens RP181110 produces the macrolide antibiotic spiramycin. After treatment with ethidium bromide, 7 strains presenting an amplified sequence of DNA (ADS) were found in its progeny. These ADS were localized within the same amplifiable region of the RP181110 genome. It has been established that these amplified strains were non-producers (Spi-) and that the loss of one particular ADS was correlated with restoration of spiramycin production. Genome rearrangements such as deletions were detected on the same side of the amplifiable region in both amplified and deamplified strains. PMID- 1641516 TI - High levels of anti-Campylobacter-flagellin IgA antibodies in breast milk. AB - Several studies have shown the beneficial role of immunity against enteric Campylobacter sp. Circulating antibodies against flagellin and possibly maternal antibodies seem to protect against intestinal colonization by Campylobacter. Milk from women in Central Africa (n = 120) and in France (n = 31) were investigated for the presence of anti-flagellin antibodies. Results showed that most French and all African milk possessed anti-flagellin IgA but not IgG. The titres of anti flagellin IgA were elevated in colostrum and decreased in later milk. Specific activities were constant during lactation, suggesting constant antigenic stimulation. The fact that IgA but not IgG are elicited against flagellin could be due to an infection limited to the mucosal surface. PMID- 1641518 TI - Social environment and health--a social epidemiological frame of reference. AB - Growing interest in epidemiological studies and prevention has led to increased awareness of the importance of the social environment to health. In this field of research, which might be designated social epidemiology, there is today extensive research into the possible association between different types of social factors and ill-health in the population. This article presents a social epidemiological frame of reference and some social factors of importance when one is studying the relationships between the social environment and health. Important social factors in the model are social stratification, social network, social support and life style factors. Two other main categories of social factors in the model are circumstances and events related to social stratification or occupation and social network respectively. These may be factors in the external or internal work environment and variables describing the general activity level of the individual or different types of stressful social network-related life events. Other important factors in the model are physiological and clinical factors and three different types of health indicator. In the field of social epidemiological research, there is an increasing need for the development of theoretical models and frameworks as support in the analysis of social factors and health. These could be based on experience and tradition in both epidemiological research and the social sciences. PMID- 1641519 TI - Traditional risk-factor profile fails to explain striking geographical differences in IHD mortality among middle-aged men. The project "myocardial infarction in mid-Sweden". AB - An east-west gradient in cardiovascular mortality has been reported from the region of mid-Sweden. Postal questionnaire studies found that the risk factor distributions among middle-aged men were similar in areas with striking differences in cardiovascular mortality. In this study, 120 randomly selected 50 year-old men in two high mortality communities in the west and 120 men from two low mortality communities in the east were invited to a health survey in which serum lipids and other risk factors were analysed. Total serum cholesterol, LDL cholesterol, HDL-cholesterol, and triglyceride levels were similar. Among fatty acids, stearic acid was high and arachidonic acid was low in the high mortality area. The levels of other traditional risk factors were the same. After taking these differences into account, the mortality differences remain large. PMID- 1641520 TI - Morbidity in early childhood, sex differences, birth order and social class. AB - STUDY OBJECTIVE: The aim of the study was to investigate the relationship between morbidity in early childhood and gender, birth order, and social class. DESIGN: The study used data collected in the Nijmegen Continuous Morbidity Registration. All presented morbidity and a number of personal data were available. SETTING: The survey population was regional; four general practices in the east of The Netherlands. PARTICIPANTS: The study population included all children born in the four practices from 1971 to 1984. They were followed up till the age of five (1537 children). MEASUREMENTS AND MAIN RESULTS: Morbidity of children in the first five years was allocated to three degrees of seriousness and to 14 diagnosis groups. The morbidity of all children was analysed for boys and girls, first-born, second-born, and later-born children, and low, middle, and high social class. Boys presented more morbidity than girls; in particular, nervous disorders, lower respiratory tract infections, and accidents. First-born children presented more morbidity than later-born children; in particular, non-serious diseases, nervous disorders, and colds. Lower social class children presented more moderately serious and non-serious morbidity, colds, lower respiratory tract infections, and skin diseases. Logistic regression analysis showed that high social class, being the first-born child, and male gender were the most important factors related to presented morbidity in general practice. CONCLUSIONS: High social class, low social class, gender, and being the first-born child were, in this sequence, related to morbidity in early childhood presented to the general practitioner in this study population. PMID- 1641521 TI - Follow-up appointments at consultation clinics: consultants fail in knowing their own practice. AB - In National Health Care Systems excessive reappointments at consultative clinics can result in over utilization of those services and/or too much retention of patients which frustrates family physicians in their interest for continuity of care for chronic patients. In order better to understand many consultants' complaints about overwork, we examined the proportion of patients who were given follow-up appointments by type of specialty in 2840 consecutive services requested in a multispecialist centre of a prepaid system in Israel, analysing as well the suspected disparity between this proportion and the consultants' perceptions on this subject. The results of this study show that 44.7% of patients at consultant clinics were given follow-up appointments, and that there was a marked disparity between the real and the subjectively estimated rates of follow-up in surgical specialties (rate-ratio 2.4). This suggests that a problem exists in the knowledge that consultants have of the structure of their own practices. PMID- 1641522 TI - Risk factors for admission to a nursing home. A study of elderly people receiving home nursing. AB - Risk factors for permanent admission to a nursing home were studied in a prospective study of persons 70 years and over who received home nursing. Demographic data and use of psychotropic drugs were registered, and mental capacity, behaviour, and performance of activities of daily living (ADL-function) estimated. 214 patients received home nursing. 166 patients were available for the follow-up study after 16 months, of whom 31 had been admitted to a nursing home. Senile dementia and stroke were the most frequent diagnoses of admitted patients. Mental impairment, age, and amount of home nursing were associated with permanent admission to a nursing home. The odds for being admitted were 10.2 (C.I. 2.3-44.4) times higher in moderately and severely mentally impaired persons than in not mentally impaired persons. The odds for admittance for those 85 years and over, compared with those younger than 80, were 5.0 higher (C.I. 1.6-15.6); and those receiving home nursing three times weekly or more had 3.8 (C.I. 1.4 9.8) times higher odds than those with less help. PMID- 1641523 TI - Age and sex: underestimated selection criteria for referral to x-ray examination of the colon? AB - An analysis was made of 2416 consecutive patients who underwent a double-contrast barium enema at the Central Roentgen Institute in Oslo. Age, sex, and radiological findings were registered. The age and sex distribution among patients consulting in general practice and in our study was surprisingly similar. This suggests that age as a risk factor for colorectal neoplasms did not play a prominent role among the referring doctors. Colorectal cancer was more frequent in males (4%) than females (2%) (p = 0.03). Odds ratio adjusted for age was 2.1 (1.3-3.8). This may be due to few examinations performed in old age, and different patient behaviour when experiencing colorectal symptoms. The overall polyp frequency was 11%. The frequency increased significantly from the age group 40-49. PMID- 1641524 TI - Oestriol in the prophylactic treatment of recurrent urinary tract infections in postmenopausal women. AB - A block randomized, double-blind, group-comparative, placebo-controlled study was conducted to assess the effect of oestriol on recurrent urinary tract infections in postmenopausal women. 40 women, median age 78 years (66-91), 20 in each group, were treated with oestriol three mg p.o. per day or corresponding placebo for four weeks, followed by one mg per day for eight weeks. The main response parameter was the number of urinary tract infections per week in the two treatment periods. Both oestriol and placebo reduced the number of infections per week significantly in both periods, compared with the pretreatment period. There was no difference between oestriol and placebo treatment in the first period. In the second period, however, oestriol treatment was significantly more effective than placebo (p = 0.05). Correspondingly, there was a significant difference between the two groups in the vaginal pH at the end of the study (p less than 0.05). We conclude that oestriol reduces recurrent urinary tract infections in postmenopausal women. PMID- 1641525 TI - Early detection of patients with fast progressive asthma or chronic bronchitis in general practice. AB - The morbidity and mortality due to asthma and chronic bronchitis are still rising in several countries. The aim of this study was to investigate whether early detection of patients with fast progressive asthma or chronic bronchitis in general practice was possible from a cross-sectional assessment of symptoms, smoking behaviour, quality of life, physical signs of the chest, allergy, and lung function. Data of 162 patients who had participated in a long-term randomized controlled intervention study in general practice were analysed. Fifty six out of the 162 patients showed fast progressive disease (FPD, a rapid annual decline in FEV1 in combination with a high exacerbation rate). Measurements at the start of the study were used in a logistic regression analysis in order to detect the patients at risk (with FPD). A lower maximal expiratory flow at 50% of expired volume (MEF50) was related to an increased risk of FPD in both asthma and chronic bronchitis (relative risks of 16.8 and 8.0 respectively, p less than 0.05). Most lung function indices, but also quality of life and pack years, were significant predictors of FPD in chronic bronchitis (p less than 0.05). However, it was not possible to detect FPD reliably with these predictors separately or even with the combination of several relevant clinical variables; 18% of the patients with chronic bronchitis and 22% of the patients with asthma were still misclassified. It was concluded from this study that more than one measurement over time (monitoring) is necessary to detect the patients at risk. Monitoring should include assessments of objective ventilatory function indices (PEFR, FEV1 or MEF50). PMID- 1641526 TI - Case-mix analyses in long-term care institutions in Stockholm. AB - In order to describe the patient case-mix in long-term care, several methods have been developed. One resource-based method, Resource Utilization Groups, RUGs, developed in New York and validated in several U.S. states, has also been validated in Stockholm and used there for studying various types of geriatric institutions. The variables used in this analysis, the distribution of the RUG categories, an ADL-index, and a case-mix index, show differences between geriatric departments, local nursing homes, mixed institutions, and private nursing homes. The geriatric departments show a high percentage of patients undergoing rehabilitation, a high case-mix index, and a relatively low ADL-index. In the local nursing homes, there is a majority of patients with behaviour problems and reduced physical functions. They show a low case-mix index but also a low ADL-index. Mixed institutions show results lying between these two types of institutions. The costs of the institutions, however, do not correlate well to the case-mix. This raises issues on efficiency and the need for new reimbursement models in geriatric care. PMID- 1641527 TI - Should we accept your article? PMID- 1641528 TI - Separation and distress--sickness absence and health screening in newly divorced middle-aged Swedish men. AB - The present study aimed at a description of the sickness absence pattern during 1982-1989 in 32 men who divorced in 1984. Another purpose was to carry through a health screening of the men within six months after the marital disruption focusing on risk factors concerning cardio-vascular disease (smoking, overweight, hypertension) and high alcohol consumption (elevated GGT). The year of divorce and the successive three years (1984-1987) were characterized by high sickness rates (average 21,7 days/year, variation 19,4-26,6) compared to a reference group (average 16,6, variation 14,9-18,1). In the remaining four years (1982-1983 and 1988-1989) the sickness absence was lower in the divorced group (average 12,2, variation 8,7-18,0, reference group: average 17,3, variation 14,8-20,0). The increase was mainly due to short absence periods (self-certifications). The health screening (health examination and record analysis) (n = 29) revealed high frequency of daily smoking and alcohol overconsumption. Overweight and hypertension were not overrepresented. The findings are discussed in relation to a supposed male reaction style to separation. The impact of social isolation is stressed. PMID- 1641529 TI - Health of the elderly with regard to sleep and nocturnal micturition. AB - A questionnaire study was carried out among pensioners in Jamtland County, Sweden. The questionnaire was answered by 1,115 persons, representing a response rate of 74%. It covered various aspects of health, with emphasis on sleep, fatigue, thirst, and other symptoms that may interfere with night-time sleep. The data were analysed with regard to the stated number of night-time disturbances due to urination. Nocturnal micturition was often associated with increased sleep disorders, a poorer quality of sleep, increased thirst, particularly at night, and increased fatigue in the daytime. All the relationships were clearer in women than in men. There was no relationship between reported enuresis in childhood and an increased frequency of voiding when the subject became older. PMID- 1641530 TI - The content of the oral daily reports at a long-term ward before and after staff training in integrity promoting care. AB - This study was based on the assumption that the daily report between different caregivers are of great importance for the quality of the care delivered and that they guide the content of it. The staff of a nursing home ward were given training in integrity promoting care and special training in reporting. After a three months' intervention period effects on patients and staff were evaluated and compared with a control ward. Positive patient outcomes have been reported earlier. The aim of this study was to describe the content of the oral daily reports between staff members in long-term care and investigate whether some changes occurred after training that might have contributed to the positive results for the patients. Another aim was to assess whether the staff regarded the reports as satisfactory. Oral reports were tape-recorded before and after staff training. A content analysis by a scheme based on Henderson's description of components of nursing care and a form analysis based on the nursing process were made. The reports were highly task oriented and the staff often discussed the patients' reaction in vague and general terms. The steps of the nursing process did not seem to be used. The answers to a questionnaire about the staff's satisfaction with the oral reports showed some increasing dissatisfaction and also comments about needs of more collaboration between different groups of personnel. More messages were given per report after the intervention compared to the control ward and the messages with psychosocial content had doubled.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641531 TI - Risk factors responsible for patients' falls. AB - The study determined intrinsic factors which contributed to the falls of adults hospitalized in a general hospital during 1987-88. Two hundred and fourteen patients were studied in two groups. Group A consisted of 108 patients who fell during their hospitalization and control Group B consisted of 106 patients with the same characteristics also hospitalized during the same period who did not fall. Of the 23 variables which have been analyzed by the multivariate logistic regression method, seven present statistically significant incidence and increased risk of patients' falls: (1) gender: the number of accidents occurring among male patients was higher than that among females (p = 0.0022); (2) age: the majority of accidents occurred in the 65 greater than or equal to years old age group (p = 0.00426); (3) general pathological conditions: mostly patients with cardiac problems (p = 0.0062); (4) neoplasms (p = 0.0334); (5) anaemias (p = 0.0128); (6) post-operative conditions (p = 0.0063); and the taking of hypnotic/tranquilizer drugs (p = 0.0486). Other significant findings were: the highest incidence of falls occurred during the first 4 days of the patients' admission to hospital and most during the early morning hours (5-6 am). Injuries incurred were bruises (32.4%), minor injuries (24%), major injuries (16.7%) and fractures (10.2%). The high correlation between patients' falls and (1) specific diseases, namely neoplasms, anaemias, cardiac and post-operative conditions and (2) the taking of hypnotic/tranquilizer drugs are risk factors in relation to patients' falls in general hospitals. PMID- 1641533 TI - The European Association of Science Editors. PMID- 1641532 TI - The alleviation of suffering--the idea of caring. AB - Caring science is seeking a basic category or the primary form of caring, the focus of caring science which includes the meaning of caring. Caring science does not deny the presence of suffering, even though it aims at soundness and health; suffering is the point from which it begins. Not until the patient has come to terms with his suffering can he hope to recover. Suffering is the most important basic category of all caring. It gives caring a unique quality and soundness and is something which all forms of caring aim to alleviate. Real caring is not just an abstract idea, philosophy or ideology, it is concrete work confronting suffering in real situations. PMID- 1641534 TI - Medical laboratory technologists' perception of professional self. A study of Swedish MLTs employed in clinical chemistry. AB - The subjective perception of professional self was studied for a sample of Medical Laboratory Technologists (MLTs) employed in Clinical Chemistry in Sweden. The sample (N = 488) consisted of a randomized tenth of members of their trade union. A mailed questionnaire with 21 items concerning self-description compared with peers in a seven-point Likert type scale was completed by 332 (68%). There was no significant overall difference concerning the four principal types of workplace: Clinical Chemistry, Blood Serology, Primary Care and Clinical Chemistry/Blood Serology. The main difference was found between those in managerial posts (N = 72) and the other MLTs (N = 260). Factor analysis showed three principal components, labelled Professionalism, Work Ethic, and Empathy, but also a different composition of variables of the components for the manager group compared with the non-manager group. PMID- 1641535 TI - Knowledge, expectations and experiences of patients receiving chemotherapy for breast cancer. AB - The experiences of a cohort of 60 women receiving chemotherapy in treatment of breast cancer were monitored in an in-depth prospective study. The purpose of the investigation was to identify ways in which nurses could improve the preparation and support of patients undergoing chemotherapy. It was found that patients' knowledge of chemotherapy was limited and that the side-effects they experienced, and their reactions to these, were rather different and more diverse than had been expected. The study illustrates the value of exploring patients' perceptions of their problems and needs for information and support. PMID- 1641536 TI - Variation in obstetric interventions by midwife. AB - This paper reports variation in birth interventions by 25 midwives among 2,135 births in a Finnish hospital. The rate of cesarean sections varied from 0 to 18%, and that of instrumental deliveries from 0 to 8%. Mother's and infant's characteristics and rates of vaginal breeches suggest that a low rate of cesarean sections was not explained only by selection to easy births. This study suggests that the skills, attitudes and routines of midwives may explain part of the variation found in birth interventions. PMID- 1641537 TI - Patient involvement in decision-making in surgical and orthopaedic practice. Effects of outcome of operation and care process on patients' perception of their involvement in the decision-making process. AB - As part of the project Perioperative Risk,--an epidemiological study of complications associated with surgical and orthopaedic operations--the article reports a study of patients' perception of their involvement in decision-making in medical consultations, and how the outcomes of surgery and subsequent care determine patients' evaluation of the treatment. Patients' view of their involvement in the decision-making process was obtained before as well as after surgery. The results reveal that the more satisfied the patients were with the outcome of the operation, and the post-operative situation, the more they were inclined to assume responsibility for the decision to have surgery. The opposite response pattern, indicating a negative evaluation of either the operation or the post-operative care, resulted in an outcome where patients described others- especially the physician--as being responsible for the decision to have surgery. The results suggest that patients' evaluations of surgery are based upon a more global reaction to what happened during the entire care process. Dissatisfaction with either the operation or the post-operative care leads to a negative outcome in terms of patients' perceptions of their own involvement. This emphasizes the importance of all health care professionals seeing themselves as a team with complementary responsibilities for success in health care. PMID- 1641538 TI - Diagnostic reasoning in the care of a vocally disruptive severely demented patient. A case report. AB - In order to investigate the effect of nursing investigations based on diagnostic reasoning and research findings on vocally disruptive behaviour in a severely demented patient a single subject study was set up. The nursing diagnoses described problems that seemed connected with sensory deprivation and care that had not been adapted to the patient's abilities. The vocally disruptive behaviour decreased when the nursing treatment plan was followed. When the caregivers stopped following the care plan the disruptive behaviour increased. Another intervention was made and once again the disruptive behaviour decreased. In conclusion the study showed that nursing diagnoses and orders were not enough. The caregivers must also understand the importance of following the care plan and cope with the emotional reactions evoked by the care. Effective leadership, regular supervision of and support to the caregivers seem necessary. PMID- 1641539 TI - The role of massage in preparation for and recovery from exercise. An overview. PMID- 1641540 TI - Physiology applied to field hockey. AB - Field hockey is a sport with a long history that has undergone quite rapid and radical change within the past decade. The advent of the synthetic playing surface has changed the technical, tactical and physiological requirements of the game at all levels, but in particular at the elite level. In order to cope with the technical evolution within the game, the hockey player has also had to develop physiologically to meet the physical standards required at elite levels. Analysis of the physiological cost and energy expenditure of playing hockey has placed it in the category of 'heavy exercise', with reported VO2 values during a game of 2.26 L/min. Energy expenditure has been estimated to range from 36 to 50 kJ/min. Physiological profiling of female hockey players has shown that somatotype tends towards 3.5/4.0/2.5. Figures for percentage body fat in female players range from 16 to 26%. Anaerobic power output has been shown to compare favourably with other groups of sportswomen and has also been shown to be a discriminating factor between elite and county level female players. Aerobic power amongst female players has been shown to range from 45 to 59 ml/kg/min. The reported somatotypes of male hockey players have shown considerable variation but there seems to be a trend away from ectomorphy towards mesomorphy. Anaerobic power output in male players has been shown to be the same as that of soccer players and better than other sports, e.g. basketball and also higher than reference norms. The range of aerobic power reported in the literature is 48 to 65 ml/kg/min and it would appear that an aerobic power in excess of 60 ml/kg/min is required for elite level play. The physical strain of hockey play has been shown to be considerable, in particular with respect to spinal shrinkage. There is a greater injury risk inherent in playing on synthetic surfaces than on grass. PMID- 1641542 TI - Energy expenditure, aerodynamics and medical problems in cycling. An update. AB - The cyclist's ability to maintain an extremely high rate of energy expenditure for long durations at a high economy of effort is dependent upon such factors as the individual's anaerobic threshold, muscle fibre type, muscle myoglobin concentration, muscle capillary density and certain anthropometric dimensions. Although laboratory tests have had some success predicting cycling potential, their validity has yet to be established for trained cyclists. Even in analysing the forces producing propulsive torque, cycling effectiveness cannot be based solely on the orientation of applied forces. Innovations of shoe and pedal design continue to have a positive influence on the biomechanics of pedalling. Although muscle involvement during a complete pedal revolution may be similar, economical pedalling rate appears to differ significantly between the novice and racing cyclist. This difference emanates, perhaps, from long term adaptation. Air resistance is by far the greatest retarding force affecting cycling. The aerodynamics of the rider and the bicycle and its components are major contributors to cycling economy. Correct body posture and spacing between riders can significantly enhance speed and efficiency. Acute and chronic responses to cycling and training are complex. To protect the safety and health of the cyclist there must be close monitoring and cooperation between the cyclist, coach, exercise scientist and physician. PMID- 1641541 TI - Oxidation of carbohydrate ingested during prolonged endurance exercise. AB - Classic studies conducted in the 1920s and 1930s established that the consumption of a high carbohydrate (CHO) diet before exercise and the ingestion of glucose during exercise delayed the onset of fatigue, in part by preventing the development of hypoglycaemia. For the next 30 to 40 years, however, interest in CHO ingestion during exercise waned. Indeed, it was not until the reintroduction of the muscle biopsy technique into exercise physiology in the 1960s that a series of studies on CHO utilisation during exercise appeared. Investigations by Scandinavian physiologists showed that muscle glycogen depletion during prolonged exercise coincided with the development of fatigue. Despite this finding, attempts to delay fatigue during prolonged exercise focused principally on techniques that would increase muscle glycogen storage before exercise. The possibility that CHO ingestion during exercise might also delay the development of muscle glycogen depletion and hence, at least potentially, fatigue, was not extensively investigated. This, in part, can be explained by the popular belief that water replacement to prevent dehydration and hyperthermia was of greater importance than CHO replacement during prolonged exercise. This position was strengthened by studies in the early 1970s which showed that the ingestion of CHO solutions delayed gastric emptying compared with water, and might therefore exacerbate dehydration. As a result, athletes were actively discouraged from ingesting even mildly concentrated (greater than 5 g/100ml) CHO solutions during exercise. Only in the early 1980s, when commercial interest in the sale of CHO products to athletes was aroused, did exercise physiologists again begin to study the effects of CHO ingestion during exercise. These studies soon established that CHO ingestion during prolonged exercise could delay fatigue; this finding added urgency to the search for the optimum CHO type for ingestion during exercise. Whereas in the earlier studies, estimates of CHO oxidation were made using respiratory gas exchange measurements, investigations since the early 1970s have employed stable 13C and radioactive 14C isotope techniques to determine the amount of ingested CHO that is oxidised during exercise. Most of the early interest was in glucose ingestion during exercise. These studies showed that significant quantities of ingested glucose can be oxidised during exercise. Peak rates of glucose oxidation occur approximately 75 to 90 minutes after ingestion and are unaffected by the time of glucose ingestion during exercise. Rates of oxidation also appear not to be influenced to a major extent by the use of different feeding schedules.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1641544 TI - Application of lasers in bladder cancer. AB - The Nd:YAG laser enables endoscopic destruction of bladder tumors under excellent viewing conditions in a specific and calculable way for induction of homogeneous necroses with simultaneous occlusion of blood and lymphatic vessels. The low local relapse rate, in contrast to that with TUR, is remarkable. By Nd:YAG laser application in combination with or without pelvic lymphadenectomy we were able to reduce the cystectomy rate significantly in recent years. PMID- 1641543 TI - Cerebral concussion in sport. Management and prevention. AB - This article explains the various stresses (tensile, compressive, and shearing) that can affect the brain, and how they may produce the different types of brain injury. The biomechanical forces and dynamics that produce coup versus contra coup injury are covered, as are the common intracranial athletic head injuries, i.e. concussion and the various intracranial haematomas (epidural, subdural, subarachnoid and intracerebral). Though less common in occurrence, because their outcome is so catastrophic, space is also devoted to the recognition, the treatment and (especially in the latter case) the prevention of the malignant brain oedema syndrome of the adolescent and the second impact syndrome of the adult. A major emphasis of this paper is the recognition of the 3 grades of cerebral concussion and the delineation of clear guidelines as to when it is safe to return to collision sports after sustaining such injuries, for the first, second or third time during a given season. Clear guidelines are also presented as to when to discontinue collision sport competition for the remainder of the season after multiple concussions. Because of the concern for the second impact syndrome, the requirement to never allow an athlete with postconcussion syndrome symptoms to return to competition is emphasised. Also covered is the prevention of head injuries, which sports are at greatest risk, and the need for additional research on the cumulative effects of concussion. PMID- 1641545 TI - Current status of lasers in neurosurgical oncology. AB - During the past decade and a half, the photothermal and photochemical effects of several medical lasers have been studied for the clinical treatment of benign and malignant, primary and secondary central nervous system tumors. Increased precision and hemostasis during tumor excision while limiting manipulation and retraction of nervous tissues are possible with the microsurgical carbon dioxide, argon, and frequency doubled neodymium:YAG lasers. Computerized tomography and magnetic resonance imaging-directed volumetric tumor removal by laser is feasible with computer-generated visual displays referenced to the patient's anatomy using stereotactic instrumentation. Photodynamic therapy with hematoporphyrin derivative as the photosensitizer and neodymium:YAG laser hyperthermia are currently under evaluation for the treatment of residual and recurrent malignant tumors. Encouraging results have been reported for each of these nonablative forms of laser use. PMID- 1641546 TI - Interstitial photoablative laser therapy guided by magnetic resonance imaging for the treatment of deep tumors. AB - The failure rate of cancer treatment remains unacceptably high, still being a leading cause of mortality in adults and children despite major advances over the past 50 years in the fields of surgery, radiation therapy, and, more recently, chemo and immunotherapy. In the United States, the 5-year survival rate for all cancers in the population has increased by only approximately 10% since 1960. Surgical access to some deep tumors of the head and neck and other areas often require extensive dissections with residual functional and cosmetic deformities. Repeated treatment is not possible after maximum dose radiotherapy and chemotherapy is still limited by its systemic toxicity. An attractive solution to these problems would be the development of a new adjunctive method combining the best features of interstitial laser phototherapy for selective tumor destruction via minimally invasive techniques for access and 3D-magnetic resonance imaging (MRI) as a monitoring system for laser-tissue interactions. Our experience with this new technique is reviewed. PMID- 1641547 TI - Interstitial laser hyperthermia. AB - Experimental studies have shown that once the appropriate laser parameters are defined, interstitial laser hyperthermia (ILH) can produce well-defined, predictable tissue necrosis in solid viscera which heal safely with little functional or structural sequelae. Preliminary clinical studies have illustrated that ILH is simple to perform, is well tolerated producing radiological and histological evidence of necrosis in liver, pancreatic, and breast cancer. Its future role in most cases will be palliative, controlling local tumour growth. Where the extent of necrosis can be matched accurately to tumour volume, the prospect for cure exists. Further research is necessary before ILH can be regarded as an established treatment and, in particular, its influence on patient survival is worthy of further evaluation. PMID- 1641548 TI - [Surveillance and control studies of nosocomial infection (I)]. PMID- 1641549 TI - [The evaluation of the quality of care]. PMID- 1641550 TI - [Professional risk, what does the law say?]. PMID- 1641551 TI - [Hyperbaric oxygenation]. PMID- 1641552 TI - [Fulguration. A new concept in the treatment of cardiac arrhythmias]. PMID- 1641553 TI - [Skin allografts from cadavers]. PMID- 1641554 TI - [The nursing consultation in dietetics and nutrition (II)]. PMID- 1641555 TI - [Technics of continuous extrarenal purification]. PMID- 1641556 TI - [New prohibitions for smokers]. PMID- 1641557 TI - [Surveillance and control studies of nosocomial infection (II)]. PMID- 1641558 TI - [Senile dementia]. PMID- 1641559 TI - [Drugs that should not be triturated]. PMID- 1641560 TI - [Medical care nurses are lacking, what is the solution?]. PMID- 1641561 TI - [Bone marrow transplantation]. PMID- 1641562 TI - [The principal motivating element is the relationship established between professionals]. PMID- 1641563 TI - [The Ministry of Court Relations and of the Government Secretariate]. PMID- 1641564 TI - [Life in Kimbau Hospital in Zaire]. PMID- 1641565 TI - [Tobacco consumption in Spain. The economic determinants]. PMID- 1641566 TI - [The education of midwives in the European Community]. PMID- 1641567 TI - [The cardiology nurse expresses an opinion]. PMID- 1641568 TI - [The dialysis disequilibrium syndrome]. PMID- 1641569 TI - [The Port-A-Cath in pediatrics]. PMID- 1641570 TI - [Some ills of the profession. The shortage of nurses and its possible solutions]. PMID- 1641571 TI - Quantization error in clinical pure-tone audiometry. AB - The current clinical procedure for pure-tone audiometry was analysed for statistical measurement errors. Theoretically, the root-mean-square (RMS) error in a single threshold measurement is always greater than the standard deviation (SD) of measured intra-individual test-retest differences, divided by the square root of two. The RMS error includes an additional quantization component, caused by the finite step size between presented signal levels. In Monte-Carlo simulations with 2-dB and 5-dB steps the quantization error was negligible compared with other errors. Therefore, the single-test RMS error can be estimated with sufficient accuracy from the test-retest SD. The simulated single-test RMS error decreased from about 2.7 dB about 2.3 dB when the audiometric step size was reduced from 5 dB to 2 dB. Hearing thresholds appeared to be about 1.7 dB better with 2-dB steps than with 5-dB steps. PMID- 1641572 TI - Auditory and psychological factors in 'auditory disability with normal hearing'. AB - Patients who have 'Auditory Disability with Normal Hearing' (ADN) complain of hearing difficulties even although their hearing is audiometrically 'normal'. The auditory and psychological factors involved in ADN have been investigated by comparing 20 patients of employment age with 20 controls (matched for age, sex and socioeconomic group) on appropriate auditory tests and questionnaires. From the results it was concluded that both auditory and psychological factors are involved in ADN. The principal finding was that as a result of their problems with discriminating speech in noise, individuals with ADN have a tendency to anxiety, depression and loneliness. In addition the otological history of an individual was found to be important in the development of ADN. Finally, it was suggested that bad coping strategies may lead to increased anxiety in those with ADN. PMID- 1641573 TI - High-frequency audiometry. Masking of air- and bone-conduction signals. AB - Interaural attenuation has been investigated for both air-conduction and bone conduction signals in the frequency ranges 0.25-18 and 0.25-16 kHz respectively. Ear canal occlusion is recommended when using the Koss HV/1A earphone for BC masking, as acoustic transmission occurs through the headset in the high frequency range. Minimum masking levels for 1/3-octave filtered white noise were established for bone-conduction signals in the frequency range 8-16 kHz. Central masking of bone-conduction signals proved to be of the same order of magnitude in the conventional- and high-frequency ranges, while the cross-masking level was approximately 10-15 dB lower above 6 kHz. Recommendations are made for a masking procedure in the high frequency range. PMID- 1641574 TI - Speech recognition in noise when wearing amplitude-sensitive ear-muffs. AB - Speech recognition in background noise when wearing amplitude sensitive (non linear) ear muffs was studied in the laboratory in 15 young normal-hearing test subjects. Low-redundancy sentences were presented from a loudspeaker in a background noise level of 70 dB (A) and the speech-to-noise (S/N) ratio yielding 50% correctly recognized words was determined. Three background noise spectra were tested: white noise, low-pass filtered noise (-12 dB/octave) and high-pass filtered noise (12 dB/octave). Five listening conditions were used: no protectors, a pair of normal ear-muffs, a passive amplitude-sensitive ear-muff and two types of electronic amplitude-sensitive ear-muffs. An ANOVA shows that speech recognition is significantly influenced by type of hearing protector and by noise spectrum. The interaction between these factors was not statistically significant. In general, the test subjects obtained somewhat better speech recognition thresholds in noise when wearing electronic amplitude-sensitive ear muffs than without muffs, whereas the opposite was true for the passive amplitude sensitive and the normal ear muffs. PMID- 1641575 TI - Coherence measurements in hearing instruments, using different broad-band signals. AB - In this investigation the effect of different broad-band test signals on non linear distortion in hearing instruments was examined using coherence measurements, and the interaction between different test signals and types of automatic signal processing is explored. It is concluded that the use of coherence measurements to quantify non-linear distortion in hearing instruments is only valid for instruments without automatic signal processing. This limitation arises because interaction between type of test signal and the automatic signal processing used causes system time-variations, which influences the measured coherence function in an uncontrollable way. PMID- 1641576 TI - Models for studying the progression of hearing loss caused by noise. AB - A computer-controlled fixed-frequency Bekesy audiometer has been used together with simplified mathematical models for hearing threshold measurements and analysis in 1,796 subjects from seven different noise environments with exposures varying from less than 80 dB(A) to greater than 95 dB(A). The methods of measurement and analysis have been used to determine hearing loss caused by noise for various age groups for men and women. It has also been possible to estimate the equivalent noise level to which workers are nowadays subjected under hearing protectors and the reduction in exposure level over the past 40 years. The results illustrate the effects of noise-reduction measures and the use of hearing protectors on the development of hearing loss suffered by workers in the actual Swedish industries. PMID- 1641577 TI - Perceived sound quality in a hearing aid with vented and closed earmould equalized in frequency response. AB - Nine normal-hearing subjects listened to speech and music in a hearing aid, either through a vented earmould or a closed earmould. The complex frequency responses of the two systems were made equal by compensating the aid and closed mould combination with a digital filter. The subjects rated the perceived sound quality of the systems on seven perceptual scales and a scale for overall impression. The results of the ratings support the hypothesis that there is no difference in perceived sound quality between vented and closed earmoulds that are equalized in frequency response, provided that the perceived loudness is the same in both cases. PMID- 1641578 TI - Patient performance with two types of multiple electrode intracochlear implant. AB - The functional results of 9 persons implanted with the Symbion Ineraid and 8 persons implanted with the Nucleus cochlear implant with the F0, F1, F2 coding strategy are reported. All patients were postlingually totally deaf, the patients implanted with the Symbion Ineraid were all above 40 years of age, while the Nucleus patients were with one exception under 40 years of age. The CID Everyday Sentences Test, the Helen Test and the Speech Tracking Test showed that all patients improved their communication skills when sound through the implant was added to lip-reading. The patients' ability to understand without lip-reading was tested with the CID everyday sentences test, with the Helen test, with spondees, with three-choice vowels and with a consonant confusion test. These showed that all 9 Symbion Ineraid patients achieved some degree of open speech understanding. Four of the 8 Nucleus patients achieved some degree of open speech understanding. Difference limen tests for intensity and frequency indicated that 2 of the Nucleus patients who did not achieve open speech understanding probably had extensive cochlear nerve damage, while the remaining 2 Nucleus patients without open speech understanding had good frequency and intensity discrimination. PMID- 1641579 TI - Experimental colitis in animal models. AB - Colitis may be induced in animals by oral administration of sulfated polysaccharides (carrageenan, amylopectin sulfate, dextran sulfate), chemical irritation by rectal instillation of diluted acetic acid, delayed hypersensitivity reaction after sensitization to DNCB or after one single administration of TNBS, and Arthus reaction induced by intravenous injection of immune complexes after chemical irritation of the colon, and by chemoattractant peptides such as FMLP. It appears that all models of colon inflammation in the rat, mouse, or rabbit produce increased amounts of eicosanoids similar to that found in human colitis. Thus, animal studies provide useful information on the origin, regulation, and function of inflammatory mediators. However, with the possible exception of the cotton-top tamarin, no animal model of induced or spontaneous inflammation of the colon is analogous to human ulcerative colitis in etiology, course of disease activity, or histology (114). The observation that two different immune-mediated models gave similar results suggests that the colitis is not a specific response to delayed-type hypersensitivity or immune complex-mediated reactions but rather an unspecific, stereotype response (125). The original disturbance may not determine the nature of the lesions ultimately produced but may instead serve as an initiator of a final common immunologic pathway. PMID- 1641580 TI - Interdigestive gastroduodenal motility and cycling of putative regulatory hormones in severe obesity. AB - The aim of the present study was to evaluate interdigestive gastrointestinal motility and its coordination with plasma concentrations of motilin and pancreatic polypeptide (PP) in 14 patients with severe obesity and in 10 control subjects with normal body weight. Motor activity of the stomach, duodenum, and proximal jejunum was recorded by using an eight-lumen catheter. Blood samples were drawn for determination of interdigestive motilin and PP plasma concentrations. We observed no difference in total duration of the migrating motor complex (MMC) or of phases I, II, or III of the MMC. Gastric phase-III activity occurred less frequently in severely obese patients (only 15% originating in the stomach) than in controls (65%; p less than 0.01). Plasma motilin concentrations were decreased in obese patients in phase I (127 +/- 17 pg/ml in controls versus 87 +/- 10 pg/ml in obese), in phase II (189 +/- 26 pg/ml controls versus 134 +/- 15 obese) and in phase III (195 +/- 29 pg/ml controls versus 153 +/- 28 pg/ml obese). Peak motilin release occurred in synchrony with phase-III activity and was greater in controls than in obese patients. Plasma PP concentrations did not differ from those of controls during any phase of the MMC. These results further suggest a potential role for motilin in regulating gastrointestinal motor activity and indicate a potential defect in this regulatory mechanism in severe obesity. Whether the relationship between disordered motor activity and motilin release is etiologic with regard to the pathophysiology of obesity remains to be determined. PMID- 1641581 TI - The colon in carbohydrate malabsorption: short-chain fatty acids, pH, and osmotic diarrhoea. AB - Short-chain (C2-C6) fatty acids (SCFA) are the major anions in colonic contents and the result of anaerobic fermentation of mainly saccharides. The effects and regulation of saccharide fermentation were studied in vitro and in vivo. In vitro faecal incubation was used to study the effects of lactose, glucose, and galactose and of pH on SCFA formation. Changing the pH to below 5 or above 11 abolished SCFA formation in the faecal incubates; in the pH 5-9 interval SCFA production was high, with only minor pH dependence. Adding glucose, galactose, or lactose to the incubation system increased SCFA production, but at high saccharide concentrations (100-300 mmol/l) SCFA formation was inhibited by the pH change. In vivo disaccharide malabsorption with increasing doses of lactulose caused a decrease in faecal pH to less than 5, values inhibitory to fermentation, before the appearance of carbohydrate in faeces. In 6 of 12 volunteers diarrhoea occurred suddenly and was caused by malabsorbed non-fermented carbohydrate. The six other volunteers had a gradual increase in faecal output with lactulose dose and developed diarrhoea before the appearance of saccharide in faeces. The intake of lactulose tolerated before diarrhoea ensued varied between individuals, with the majority having diarrhoea of more than 11/day at 160 g lactulose per day. At this dose SCFA absorption was estimated to be in the range 550 to 1150 mmol/day. PMID- 1641582 TI - The importance of the centroacinar region in cerulein-induced mouse pancreatic growth. AB - Early proliferation events within different exocrine pancreatic cell compartments were studied in mice with or without cerulein administration. A technique with 3H thymidine labeling of DNA-synthesizing cells was used. Groups of five animals were given either cerulein (20 micrograms/kg/24 h) or saline subcutaneously twice daily. 3H-thymidine was given as a single injection, 300 microCi intraperitoneally, on the 3rd and 8th day of cerulein or saline administration, and the fraction of labeled cells in each cell compartment (3H-thymidine labeling index, TLI) was calculated on the basis of autoradiographic analyses of the tissue. In a second set of experiments the distribution of the tracer between cell compartments, when given on the 3rd day of cerulein (saline) administration, was followed over a 5-day period. The highest proliferative rate was observed in the centroacinar cell compartment (TLI, 6%), and newly formed cells were accumulated during the 5-day 'chase' period. During the same time the relative amount of labeled centroacinar cells increased and comprised 40% of all labeled exocrine cells. The relative size of the compartment did not increase, indicating increased cell turnover with loss of or possibly migration of centroacinar cells into other pancreatic cell compartments. Weak and no trophic effects of cerulein were seen on the acinar and ductal cell populations, respectively. In the control group labeled ductal cells were significantly reduced during the chase period. This was not observed in the cerulein group, indicating addition of labeled cells to this compartment from other sources. A significant non-cerulein-dependent relative increase and decrease of the ductal and acinar cell compartments, respectively, were observed during the chase period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641583 TI - Incidence and pattern of peptic ulcer bleeding in a defined geographical area. DUSUK Study Group. AB - Despite the introduction of effective medical treatment for peptic ulcer disease, no decrease in the incidence of bleeding has been observed. Unfortunately, most incidence studies rely on a questionable case ascertainment and poor data. We therefore conducted a prospective study, to achieve an unbiased estimate of incidence and pattern of peptic ulcer bleeding in Dusseldorf (Germany). In a 1 year period all patients with endoscopically verified peptic ulcer bleeding who were admitted to the departments of internal medicine or surgery in nine hospitals or seen by nine general practitioners offering endoscopic service were included in the study. Incidence rates were calculated in accordance with sociodemographic variables and expressed per 100,000 person-years of observation. The overall incidence of peptic ulcer bleeding was 51.4, with almost even rates for gastric (26.5) and duodenal (24.9) ulcer. Age was associated with an increased likelihood of bleeding in gastric ulcer patients of 19 per decade from about 40 years onwards (duodenal ulcer, 15). The incidence was about twice as high in men as in women (relative risk = 1.9). The pattern of peptic ulcer bleeding was similar in gastric and duodenal ulcers with regard to ulcer size, multiple lesions, and bleeding activity at endoscopy. However, patients with gastric ulcer bleeding had significantly more often accompanying or underlying diseases. No significant differences were observed between gastric and duodenal ulcer bleeding with regard to nonsteroidal antiinflammatory drug intake and ulcer history. The incidence rates in our study are in the upper range of the literature and comparable to rates from the USA and UK both before and after the introduction of H2 blockers. We hypothesize that the persistently high incidence rate is a superposition of two trends: higher incidences due to a more elderly and diseased population and more NSAID intake, and lower incidences due to effective medical treatment. PMID- 1641584 TI - Leucocyte scintigraphy to localize inflammatory activity in ulcerative colitis and Crohn's disease. AB - The validity of using autologous leucocytes labelled with technetium -99m hexamethyl-propyleneamine-oxine (Tc-HMPAO) for scintigraphy in inflammatory bowel disease was evaluated in 12 patients with clinically active ulcerative colitis (UC) and 10 with Crohn's disease (CD). Colonoscopy and biopsy were used as reference. Scintigrams taken 1 h and 3 h after leucocyte reinjection were evaluated blindly by two independent observer groups. Full agreement was found in 11 of 12 UC patients when compared with colonoscopy but in only 3 of 10 CD patients. Segments with agreement in CD patients often showed neutrophilic granulocyte infiltration at biopsy. The judgements of clinicians and physiologists differed for only 2 of totally 70 UC segments but for 13 of 59 CD segments (kappa, 0.94 and 0.52). It is concluded that Tc-HMPAO scintigraphy might be an alternative to colonoscopy in the control of disease extent in UC. In CD patients the technique might warn about infections complications. PMID- 1641586 TI - Long-term treatment with 300 mg ranitidine once daily after dilatation of peptic oesophageal strictures. AB - This clinical, double-blind, multicentre trial evaluates the long-term effect of ranitidine in patients dilated for peptic oesophageal strictures. Seventy-one consecutive outpatients were dilated with hydrostatic balloons to a diameter of 18-20 mm and randomized to a 1-year treatment with 300 mg ranitidine in the evening or with placebo. Endoscopies with measurement of the stricture size were performed before the initial dilatation, after 6 and 12 months, and in between when necessary. Symptoms and use of antacids were registered at inclusion and after 3, 6, 9, and 12 months. Thirteen patients were withdrawn before study end point. Fifteen of 30 (50%) in the ranitidine group and 11 of 28 (39.3%) in the placebo group were redilated. The difference in disfavour of ranitidine was 10.7% (95% confidence interval, -14.9; 36.2%). Nor were there any statistically significant differences between the treatment groups with regard to stricture size at end point, symptoms, or use of antacids. In conclusion, there is no evidence of any clinically significant effect of a 1-year treatment with 300 mg ranitidine once daily after dilatation of peptic oesophageal strictures. PMID- 1641585 TI - Allergen-induced mucosal exudation of plasma into rat ileum and its inhibition by budesonide. AB - Exudation of plasma across the airway mucosa is a specific defence/inflammatory response finely regulated by mediators and (in rodents) a capsaicin-sensitive innervation. This study examines plasma exudation responses to endointestinal challenges and effects of a glucocorticoid. The ileum of anesthetized rats was catheterized and ligated at two points 10 cm apart for mucosal challenge (0.5 ml) and repeated lavages (5 ml). Lavage fluid levels of the plasma tracer 125I albumin, previously injected intravenously, showed a stable, low base line greater than 2 h. Challenge with mediators (10(-5) M bradykinin, 10(-5)-10(-3) M serotonin, 10(-6)-10(-4) M histamine, 2.10(-9)-2.10(-7) M leukotriene D4 (LTD4), or 10(-5)-10(-3) M capsaicin did not increase luminal radioactivity. However, allergen (10(-6) M ovalbumin, in previously sensitized animals) produced prompt mucosal exudation of 125I-albumin, peaking within 30 min (p less than 0.001) and returning to base line within 90 min. Separate experiments suggested that absorption was not increased during the mucosal exudation. The glucocorticoid budesonide (10-1000 micrograms/kg given by gavage 24 h before challenge) dose dependently inhibited the allergen-induced exudation (p less than 0.01). The route of administration and the antiexudative versus the systemic potency (reduced thymus weight) suggest the possibility of a topical action of budesonide. We conclude that endointestinal allergen challenge produces reversible and glucocorticoid-inhibitable exudation of plasma across the mucosa. It appears less likely that bradykinin, serotonin, histamine, LTD4, or a capsaicin-sensitive innervation is involved in producing this exudative effect. PMID- 1641587 TI - Serodiagnosis of Helicobacter pylori-associated gastritis with a monoclonal antibody competitive enzyme-linked immunosorbent assay. AB - Forty-nine monoclonal antibodies against Helicobacter pylori were screened to investigate their capacity to be used in enzyme-linked immunosorbent assay (ELISA) competitive systems for the serodiagnosis of Helicobacter pylori infection. On the basis of the inhibition pattern showed by the sera of five infected patients, the antibodies were subdivided into five groups. The immunoblotting analysis showed that the antibodies recognized a total of nine different antigenic determinants. In a study of the reaction of the antibodies with 12 isolates of H. pylori a total of 9 antigenic profiles were identified. Two monoclonal antibodies, HpN44 and HpN45, which recognized a 64-kD protein, were inhibited by all 5 positive sera. Antibody HpN45 was labeled with horseradish peroxidase, and the competitive ELISA was compared with an ordinary indirect ELISA in a study of 102 patients undergoing gastroscopy. Seventy-three patients proved to be infected by H. pylori according to urease or histologic tests. The sensitivity and specificity were 90.4% and 89.6%, respectively, for the indirect ELISA and 100% and 89.6% for the HpN45 competitive assay. The three patients who were 'false seropositive' with both serologic tests had atrophic gastritis. The high diagnostic performance and simplicity of the HpN45 monoclonal competitive ELISA make it suitable for routine serodiagnosis of H. pylori infection. PMID- 1641588 TI - Does vagotomy affect the growth of the pancreas in the rat? AB - Vagotomy has been claimed to have a growth-promoting effect on the pancreas in the rat. The present study failed to show differences in total or relative pancreatic weight and DNA content between vagally intact and vagally denervated rats, whether normoCCKemic or hyperCCKemic after pancreaticobiliary diversion during 2-8 weeks. Contrary to the claims made in several recent reports, vagotomy does not seem to influence the growth of the rat pancreas. PMID- 1641589 TI - Incidence and prevalence of Crohn's disease in the county of Copenhagen, 1962-87: a sixfold increase in incidence. AB - The incidence of Crohn's disease increased sixfold from 1962 to 1987 in the county of Copenhagen. The mean annual incidence for 1979-87 was 4.1 per 10(5) inhabitants. The increase was found equally in both sexes, with an approximately 40% higher incidence in women. The maximal incidence was found in the 15- to 24 year age group, being 12.8 per 10(5) per year for women and 6.0 per 10(5) per year for men, as mean of the period 1979-87. The prevalence at the end of the study was 54 per 10(5) inhabitants, 46 per 10(5) in men and 63 per 10(5) in women. The clinical appearance of the disease at the time of diagnosis was remarkably similar during the study period with regard to both the localization of disease and the clinical symptoms and signs. A slightly higher percentage of the patients, however, were in high disease activity at diagnosis in the later years of the study. PMID- 1641590 TI - The effects of intravenous urea infusions on portal and arterial plasma ammonia and urea enrichment of jejunal and colonic infusions. Acute experiments with growing pigs. AB - Six pigs (49-69 kg) were anaesthetized and fitted with cannulas in the brachiocephalic artery and portal and jugular veins. In addition, inlet-outlet perfusion cannulas were placed in segments of the small and large intestine. Intravenous infusion of urea for 2 h increased arterial plasma urea from a base line level of 176 (SE, 51) mg/l up to 292 (SE, 67) mg/l after 5 h. During this rise portal ammonia levels remained fairly constant, with minimum and maximum values of 1.2 (SE, 0.3) and 1.7 (SE, 0.6) mg/l, respectively. The average amount of urea recovered in perfusates from small- and large-intestinal segments were 141.4 and 43.8, respectively (p less than 0.001), when expressed as micrograms/g tissue/30 min. It thus appears as if the portal blood is not an important carrier of ammonia liberated from the hydrolysis of urea and that the gastrointestinal tract is differentially permeable to urea at different levels. PMID- 1641591 TI - The main five types of viral hepatitis: an alphabetical update. AB - The rapidly increasing knowledge in the field of viral hepatitis warrants regular updates. Clinical studies with new hepatitis A vaccines have shown that they are safe, well-tolerated, and effective. Several reports on hepatitis B virus (HBV) variants have appeared. Surface antigen mutants may have an important influence on vaccine prophylaxis because existing vaccines may not protect against infection with these variants. Hepatitis D virus is a circular RNA virus that requires the presence of HBV for successful infection. The requirements for the dual expression of these viruses are unknown and their relation is complex. Hepatitis C virus (HCV) is a RNA virus that has homology with the flaviviridae. This is a rather common agent in most populations studied and often causes chronic infection but little is known about its spread. Hepatitis E virus is a RNA virus which is usually spread by contaminated water in developing countries. The disease causes high mortality in pregnant women. The existence of further viral hepatitis agents have been suggested but hard data confirming this is so far lacking. PMID- 1641592 TI - Prevalence of Mycoplasma pneumoniae in subjectively healthy individuals. AB - Subjectively healthy persons were investigated for the presence of Mycoplasma pneumoniae in throat cultures. During a peak period of M. pneumoniae incidence, 13.5% of 758 healthy volunteers were found to harbour the bacterium in the throat. The investigation was continued, and during a subsequent period of 11 months, the incidence of M. pneumoniae isolated decreased to 4.6% of 499 volunteers. All new blood donor sera 1990-1991 (422 sera) were screened for the presence of antibodies to M. pneumoniae; it was found that there was a fluctuating but significant number of individuals with positive serology based on a single test occasion. PMID- 1641593 TI - Preventing secondary cases of meningococcal disease by identifying and eradicating disease-causing strains in close contacts of patients. AB - In Norway, the use of chemoprophylaxis after cases of meningococcal disease is not recommended. Instead, household members less than 15 years are treated with penicillin for 7 days. Failures of this treatment have been reported. We therefore used DNA fingerprinting to identify the disease-causing strain in healthy contacts combined with selective rifampicin prophylaxis to these carriers to prevent secondary cases. During a 2-year period (1987-89) there were 13 cases of meningococcal disease in the County of Telemark (165000 inhabitants). 65 (14.7%) out of 441 contacts to these 13 patients harbored meningococci in their throat; 16 (3.6%) carried the disease-causing strain. Only 1 carrier fulfilled the criteria for being treated with penicillin; 8 were adults and the remaining 7 were not household members. No secondary cases of meningococcal disease occurred during the study period or the following 12 months. During the 4-year period (1984-87) preceding the study period there were 39 cases of meningococcal disease in Telemark; 7 of them were index cases for 12 bacteriologically verified and 4 clinically suspected secondary cases of meningococcal disease. We conclude that selective prophylaxis with rifampicin seems to be more efficient that penicillin treatment of household members less than 15 to prevent secondary cases of meningococcal disease. PMID- 1641594 TI - Therapy of multidrug resistant typhoid in 58 children. AB - Treatment of children with infections caused by Salmonella typhi strains resistant to the commonly used oral antimicrobials is a special problem. As children cannot be treated with quinolones, there is no form of oral therapy. Third generation cephalosporins, which have been shown to be effective against typhoid caused by ampicillin sensitive strains of S. typhi were effective against typhoid caused by ampicillin, chloramphenicol and sulfamethoxazole/trimethoprim resistant strains. We treated 28 children with ceftriaxone and 8 with cefotaxime. We found ceftriaxone to be more effective than cefotaxime with significantly lower relapse rate. Antibiotic therapy of 19 other children, initially treated in a similar manner, was altered for ease of therapy or due to poor response to therapy. The high cost of this parenteral therapy and the problems in its delivery point to the need for safe, effective oral therapy. PMID- 1641595 TI - Molecular characterization of Borrelia burgdorferi isolated from Ixodes ricinus in northern Sweden. AB - Ixodes ricinus ticks, harbouring Borrelia burgdorferi, were found in an area in northern Sweden, not thought to be endemic for Lyme borreliosis. This investigation took place at Norrbyskar, an island situated in the Bothnian Gulf, 63 degrees 33'N/19 degrees 52'E. One of 42 nymphal and 8/43 adult I. ricinus ticks collected carried spirochetes as seen by phase contrast microscopy. Pure bacterial cultures were obtained from 2 of the ticks. Western blot analysis using species-specific monoclonal antibodies showed that the isolated spirochetes were B. burgdorferi. The identity of the isolated spirochetes was confirmed by DNA amplification using B. burgdorferi OspA and flagellin gene specific oligonucleotides as well as partial DNA sequencing of the respective OspA and flagellin genes. The 2 isolated spirochaete populations were different as shown by their protein profiles in sodium dodecyl sulphate polyacrylamide gels. Moreover, the demonstration of Lyme borreliosis in a patient from the island of Norrbyskar indicates the need for clinical consideration of this disease in northern Sweden. PMID- 1641596 TI - Loss of erythrocyte complement receptors (CR1; CD35) in patients with acute episodes of septicaemia or bacterial meningitis. AB - 14 patients with septicaemia or bacterial meningitis were examined for serum levels of erythrocyte complement receptors CR1 (C3b/C4b; CD35) by an enzyme linked immunosorbent assay and levels of circulating immune complexes (IC) by a polyethylene glycol precipitation complement consumption method, and concentrations of complement C3d split products in plasma by intermediate gel rocket immunoelectrophoresis. The CR1 receptor levels were significantly lower on day 7-8 after admission than on day 1-2 (p = 0.01), and than the levels 3-4 months later (p = 0.002). Both the levels of IC in serum and the C3d concentrations were significantly higher on day 7-8 than 3-4 months later (p = 0.02 and p = 0.004). The mechanism behind a temporary decreased expression of CR1 in patients with acute episodes of septicaemia or purulent meningitis is not fully known, and further investigations are needed to clarify whether this reduction in erythrocyte CR1 causes an impaired disposal of IC in patients with infections. PMID- 1641597 TI - Complement activation and the production of inflammatory mediators during the treatment of severe sepsis in humans. AB - Sepsis or septic shock is frequently associated with activation of the complement system, coagulation and fibrinolytic changes and the release of several cytokines. In this study we analyzed the relation of complement activation to the inflammatory mediators, hemodynamic and biochemical parameters and severity of illness and outcome in 20 consecutive patients with clinically defined sepsis. Levels of C3a and C3d were elevated in 90% of the patients (median levels 0.19 mg/l and 8.6 mg/l respectively) in comparison to 14% and 42%, respectively of 7 patients with non-septic shock. Levels of C4 were decreased in only 1 of the 20 septic patients. Levels of TNF and IL-6 were elevated in 94% and 100% of the patients, Levels of TNF and IL-6 were elevated in 94% and 100% of the patients, respectively (median levels 122 ng/l and 1300 U/ml) and were clearly interrelated (r = 0.67, p less than 0.01). C3a levels correlated with the APACHE II score (r = 0.57, p less than 0.05) and high C3a levels were associated with fatal outcome (p less than 0.05). C3a was also correlated inversely with mean arterial pressure (r = 0.50, p less than 0.01). Levels of complement C3a and C3d significantly correlated with levels of plasminogen activator inhibitor-1 (PAI) and correlated inversely with AT-III levels. We found no correlation between these complement products and leukocyte counts or lactate levels, nor was there a correlation between C3a or C3d and the cytokines TNF and IL-6. Levels of C3a and C3d did not decrease significantly during the first 24 h of treatment, in contrast to a clear decrease in IL-6 levels in all patients and a decrease in TNF in the surviving patients. TNF levels remained stable or increased in the non-survivors. We conclude that both the complement system and the cytokine system are involved in the pathogenesis of septic shock and may be involved in the development of some of the fatal complications like hypotension and disseminated intravascular coagulation. PMID- 1641598 TI - The differential leukocyte count in adults with acute gastroenteritis. AB - The total and differential leukocyte count of 4 groups of patients, admitted to the hospital because of acute gastroenteritis was evaluated. The 4 groups included: (a) 131 adult patients with positive stool culture for shigella; (b) 23 children (age less than 15 years) with positive stool culture for shigella; (c) 52 adult patients with positive stool culture for salmonella; (d) 43 adult patients with negative stool culture for bacterial pathogens. The total leukocyte count did not contribute to the differential diagnosis between shigella gastroenteritis and gastroenteritis of other etiology. However, the absolute band count was significantly higher in adults with shigella gastroenteritis. Moreover, a band to total neutrophil ratio further increased the diagnosis specificity. The differential leukocyte count can contribute to early diagnosis of shigellosis in adult patients. PMID- 1641599 TI - A comparison of aztreonam and ceftazidime in the treatment of respiratory infections in adults with cystic fibrosis. AB - A randomised double blind 2-week trial of monotherapy with ceftazidime and aztreonam was completed in 22 adults with cystic fibrosis. 26 courses of treatment were initiated and 22 courses were completed. Within groups, both ceftazidime and aztreonam demonstrated a significant improvement in FEV1 at 2 weeks (ceftazidime p less than 0.05; aztreonam p less than 0.01) and a decline in sputum weight at 2 weeks (ceftazidime p less than 0.05; aztreonam p less than 0.05). Between groups, for spirometry and sputum weight the only change was a slower decline in FEV1 in the aztreonam group at 42 days (p less than 0.05). PMID- 1641601 TI - Enterobacter endocarditis. AB - Endocarditis due to Enterobacter species is very rare. We recently cared for a patient who developed E. cloacae endocarditis following mitral valve replacement with a porcine heterograft, and was successfully treated with antibiotic therapy alone. A review of the literature disclosed an additional 17 well-described cases of enterobacter endocarditis. Two-thirds of the patients had underlying cardiac disease. The mitral valve was most frequently involved (10/16 cases) with 4 of the patients having concomitant aortic valve involvement. The overall mortality rate was 44.4%. Antibiotic therapy of enterobacter endocarditis should consist of the combination of a beta-lactam antibiotic and an aminoglycoside with careful monitoring of blood cultures to assure the adequacy of therapy. Resistance of enterobacter to previously susceptible antibiotics may occur during therapy due to induction of a chromosomally-mediated beta-lactamase, necessitating a change in antimicrobial therapy. Valvular surgery is indicated for patients failing medical management. PMID- 1641600 TI - Efficacy and tolerance of roxithromycin in comparison with erythromycin stearate in patients with lower respiratory tract infections. AB - The efficacy and tolerance of roxithromycin 150 mg b.i.d. were compared with those of erythromycin stearate 500 mg b.i.d. in patients with lower respiratory tract infections. Out of 86 patients recruited for the study, 79 were evaluable for tolerance and 76 for efficacy. These patients were evenly distributed among the 3 investigational clinics, with 26, 25 and 28 patients, respectively. The diagnosis of lower respiratory tract infections was based on clinical, laboratory, radiological and/or physical findings and, when available, bacteriological and serological findings. The duration of treatment was 10 days, with follow-up at post-treatment visits directly after treatment and 6 weeks thereafter. The clinical outcome was satisfactory with no significant difference between the drugs. More patients reporting adverse events were on erythromycin than on roxithromycin (51.3% vs 17.5%; p = 0.003). The results suggest that roxithromycin is as effective as erythromycin stearate in the treatment of lower respiratory tract infections and causes fewer adverse effects. PMID- 1641602 TI - Transfusion associated bacteremia and septic shock due to Erwinia herbicola. AB - We report a case of severe septicemia after blood transfusion to a 61-year-old man. The patient developed septic shock with signs of disseminated intravascular coagulation already during the blood transfusion. Blood culture from the patient showed growth of Erwinia herbicola and culture from the blood bag massive growth of the same microorganism. The bag had been stored in a refrigerator for 3 weeks after tapping. It is likely that contamination occurred during the tapping procedure. PMID- 1641603 TI - Successful surgical management of septic arthritis due to Trichosporon beigelii in a patient with acute myeloid leukaemia. AB - A Greek male with acute myeloid leukaemia (AML) developed a pyrexial illness while neutropenic and Trichosporon beigelii was isolated from his skin, blood and urine. This infection appeared to resolve with a rising neutrophil count, but recurred in the next episode of neutropenia. T. beigelii was isolated from an aspirate from an inflamed knee. Despite a rising neutrophil count resolution only occurred after surgical drainage and local irrigation with miconazole. PMID- 1641604 TI - Risk factors connected with hepatitis C infections in Finland. AB - Risk factors of 160 hepatitis C virus antibody (anti-HCV) positive patients, found in our serological routine, were analyzed. 89% of the patients had been exposed to blood (64% had a history of i.v. drug abuse, 24% had used whole blood or blood products, 0.6% had a profession connected with blood exposure). 8.1% of the patients had lived or travelled in Southern countries, notably in Africa and in the Eastern Mediterranean, 0.6% had an anti-HCV positive sex partner. 2.5% of the patients had no known risk factors. PMID- 1641605 TI - Swedish norms for completion of word stems and unique word fragments. AB - Swedish norms for completion of word stems and single-solution word fragments, with few or many letters specified, were obtained from Swedish students. Comparisons were made for completion rates between stems and fragments that were possible to complete with the same word. As expected, completion rates for fragments were generally superior to those of word stems since the word stems allowed alternative completions. Adding one letter to the word stems and fragments resulted in a significant increase in the probability of completion, for both stems and fragments. A stepwise regression analysis was conducted in order to partial out factors determining the completion probability for fragments. The ratio of specified letters to blank characters, and the familiarity of the solution was found to be the most important factors. Finally, the effect of number of given letters in the word stem on the number of generated words per stem was studied. The mean number of words generated per stem was found to be equal for both two- and three-letter word stems. PMID- 1641606 TI - Observational training improves adult womens' performance on Piaget's water-level task. AB - Among women university students who lacked conceptual understanding of the principle that the surface of still water is always horizontal, a specific task procedure designed to optimize self-discovery of the principle proved effective. Successful learning was reflected in more accurate responses on an adjustment task and by a significant increase (p less than .01) in the number of subjects able to verbalize a correct strategy. In contrast to previous research the results show that adult womens' performance on the water-level task can be improved by observational training, suggesting that the female lag in spatial skills may depend on experiential factors. PMID- 1641607 TI - Self-reported change in health behaviour after a mass media-based health education campaign. AB - A comprehensive short-term fund-raising campaign, was launched in 1987 by a health charity organization in cooperation with the only Norwegian TV-channel covering the whole country. The campaign which was extensively announced on TV and other media and which involved large proportions of the population, finished up with a six hour TV-show on the fund-raising day. Because a considerable amount of information on prevention of heart disease was presented in connection with the campaign, it is presently evaluated as a nationwide health education campaign. Twenty-two per cent of the population reported changes in one or more habits in connection with the campaign (one third of them took more exercise, while one quarter reduced/quit their smoking). Health behaviour change among family/friends, reported new knowledge of health and worry created by the campaign, were the factors most clearly associated with self-reported behaviour change. The paper discusses the magnitude of the effects of the campaign in relation to the study design, and the importance of social environment and fear arousal on health behaviour. PMID- 1641608 TI - Effectiveness of negative-thought-reduction, meditation and placebo training treatment in reducing anger. AB - Twenty-nine highly angry subjects who obtained high scores on Spielberger's Trait component of State-Trait Anger Scale went through a thought-listing procedure to determine their negative self-statements in response to high, medium, and low anger-arousing situations. It was found that subjects made more negative self statements in response to a high anger-arousing situation compared to the medium and low anger-arousing situations. The subjects were divided into four groups. Subjects in one group were trained to reduce their negative thoughts, subjects in a second group were trained to meditate, subjects in the third group were asked to imagine the high anger-arousing situations (placebo procedure), and subjects in the fourth group were given no treatment. It was found that the subjects in the Negative-thought-reduction, Meditation and Placebo groups showed improvement in trait anger, anger aroused through high-anger situations, anger scores across a wide variety of situations, unconstructive coping, and anger measured through physiological symptoms. The gains made through intervention were maintained at a 6-week follow-up. The No-treatment Group showed no significant change in anger scores across a wide variety of situations, unconstructive coping, and physiological symptom scores but showed a small but significant improvement in trait anger and in anger aroused by high-anger situations. PMID- 1641609 TI - Perceptual and motor components of performance in three different reaction time experiments. AB - Three reaction time experiments were conducted to examine the effects of time of day, stimulus intensity, stimulus modality, and constant and variable foreperiod on the perceptual and motor components of performance. These variables are all supposed to generate changes in arousal level. All the independent variables affected the perceptual component, while the motor component was significantly influenced only by foreperiod and modality. The results are discussed in relation to aspects of dependency/independency of the perceptual and motor components of human performance in reaction time experiments. PMID- 1641610 TI - Reactions to DMT as related to psychotic and borderline personality organization. AB - Thirty-one inpatients in a psychiatric clinic were assessed with DMT and the Structural Interview. In order to assemble every relevant reaction that an individual might have to a percept-genesis, 130 DMT variables were formed. The results were first subjected to a quality control of the DMT-scores and then subjected to partial least squares in latent variables (PLS) discriminant analysis. The analysis showed that it is possible to separate patients with psychotic PO (PPO) from those with borderline PO (BPO) by means of the 130 variables. The BPO group is characterized by aggressive manifestations, sensitivity to threat, identity lability and various transformations of the Hero gestalt. The PPO group, on the other hand, is characterized by high threshold values for perception, lack of identity, denial and repression of the peripheral person at a late-phase level. There are other perceptual reactions that are important predictors of PO than the defence categories of the manual. These perceptual reactions do not correspond to the traditional psychodynamic defence mechanisms. Our conclusion is that principal component analysis (PCA) and PLS are useful methods of finding discriminating patterns of perceptual reactions to the DMT for patients with different PO. PMID- 1641611 TI - A qualitative aspect of learning-sensitive open field ambulation in mice. AB - Maze training was shown to affect qualitative aspects of the learning-sensitive open-field (OF) ambulation in male Swiss albino mice. The changes in thigmotactic (wall-seeking) behaviour were most pronounced when significant signs of learning occurred, usually on the third day of training. Also daily changes in thigmotaxis from before to after training were found. Mice not subjected to maze training exhibited a different thigmotactic pattern of behaviour. The present series of experiments indicated that separate starting-points (centre or wall) influenced the thigmotactic behaviour as opposed to the shape of the OF (circular or square). PMID- 1641612 TI - [Liver transplantation: current aspects from the East]. AB - The shortage of organs from cadaveric donors for liver transplantation has resulted in the development in Australia and the United States of the technique of partial hepatectomy on living related donors. As multi-organ harvesting from cadaveric donors is not accepted in Japan, procurement from living related donors is the only source of organs in this country, where active development in this field has been initiated. PMID- 1641613 TI - [Reoperation in colorectal carcinoma with curative intention]. AB - From the surgical point of view it may be helpful to adopt the following guidelines in the treatment of patients with metastatic or locally recurrent colorectal cancer: 1. A gastroenterologist concerned with oncological patients should initiate adequate resectional treatment of the primary tumor. 2. In case of locoregional recurrences, every diagnostic effort (endoscopy, intraluminal ultrasound, angiogram, CT-scan, MRI) should be made to select patients with limited and resectable disease. 3. In patients with liver metastases amenable to surgical resection it is mandatory to rule out extrahepatic disease preoperatively as far as possible. 4. Prognostic factors deriving from tumor biological data, extent of recurrent disease, and laboratory findings (CEA) must be taken into consideration when the decision whether to operate is to be made. These arguments should also be used to support non-operative treatment in patients with a type of recurrence that cannot be cured by surgery. 5. Postoperatively, all information (intraoperatively detected extrahepatic disease, tumor infiltrated resection margins, CEA not returning to normal levels) should be combined to classify patients according to whether they carry a high risk for a second tumor recurrence and should thus undergo additional treatment. In a "low risk situation", further follow-up seems to be adequate. PMID- 1641614 TI - [Rhabdomyolysis, acute renal insufficiency and hypercalcemia]. AB - Acute renal failure is a severe and frequent complication of rhabdomyolysis. During the early polyuric phase, hypercalcemia is observed in around 30% of cases. The principal mechanism is the liberation of calcium from areas of muscular necrosis. Two cases of toxic rhabdomyolysis with secondary hypercalcemia are described. PMID- 1641615 TI - [The long road to the fever chart]. AB - Temperature and pulse measurement have a central position in the history of medicine in the 19th century as well as the medicine of today. Its beginnings can be traced back a long way; naturally, they are closely linked to the development of the thermometer and the watch, but their long paths also touch on the history of science and culture. Knowledge and teachings of pulse and fever certainly did not develop simultaneously and in mutual agreement, but crossed one another's paths on two occasions: in the work of Boerhaave in the early 18th century and with the introduction of thermometric analysis into the clinic from the middle of the 19th century. Individual milestones are selected and described. PMID- 1641616 TI - [Physiological basis of high milk production in cattle]. AB - Milk yield is determined by number, size, synthetic and secretory capacity of mammary alveolar cells and low amounts of residual milk after milking. Initial milk yield and persistency of lactation are important. Important factors to achieve high milk yield are: optimal mammary development and preparation to lactation; maintenance and possibly increase in number and of synthetic capacity of alveolar cells during established lactation; sufficient availability of substrates for milk synthesis through high feed intake, readiness to mobilize body reserves (especially depot fat) and increased mammary blood flow; optimal milk let-down; regular and possibly more than twice milking/day. Favorable for a high milk yield are high circulating concentrations of somatotropin, possibly associated with increased production and levels of the insulin-like growth factor I, in the presence of low concentrations of and reduced sensitivity or responsiveness of target organs to insulin, reduced circulating levels of thyroid hormones and possibly enhanced conversion of thyroxine to triiodothyronine in the mammary gland. Enhanced sensitivity of depot fat to lipolytic hormones is favorable for high milk production. PMID- 1641617 TI - Ultrasonographic findings in a cow with ascites due to thrombosis of the caudal vena cava. AB - This case report describes a three-year-old Swiss Braunvieh cow with ascites due to thrombosis of the caudal vena cava. Ultrasonography verified the ascites and revealed dilatation of the abdominal portion of the caudal vena cava (4.8 cm). It was presumed that the caudal vena cava was occluded by a thrombus or by perivenous compression cranial to the dilatation. Post mortem findings included: a massive accumulation of fluid in the abdominal cavity; a 15 cm long thrombus in the subphrenic region of the caudal vena cava; multiple pulmonary abscesses; severe thrombosis of the pulmonary vasculature; hepatic congestion; oedematous abomasal folds; and severe thrombophlebitis of the left jugular vein and both udder veins, due to poor intravenous injection technique. Ascites caused by thrombosis of the caudal vena cava is rare because collateral routes of venous return, including the udder veins, are usually established. It was therefore concluded that the ascites was attributable to bilateral thrombosis of the udder veins. PMID- 1641618 TI - Material help. PMID- 1641619 TI - Biotechnology for sale, cheap. PMID- 1641620 TI - Doomsday diagnostic? PMID- 1641621 TI - Aborting research. PMID- 1641622 TI - East of Eden. PMID- 1641623 TI - Sea sick. PMID- 1641624 TI - Keeping it in the family. PMID- 1641625 TI - Bacterial endotoxins. AB - Endotoxins possess an intrinsic fascination that is nothing less than fabulous. They seem to have been endowed by nature with virtues and vices in the exact and glamorous proportions needed to render them irresistible to any investigator who comes to know them. PMID- 1641626 TI - Evolution comes to life. PMID- 1641627 TI - Paradoxes of musical pitch. PMID- 1641628 TI - Reference values for the study of low doses. AB - At present, the quantitative differences between environmental exposure and occupational exposure to toxic metals are steadily decreasing, it becomes important to establish reference values of the tests used for biological monitoring. However, the word 'reference values' is often used inappropriately and in particular its significance is often confused with that of 'limit values' or 'normal values'. The term reference values defines the levels of the biological indicators in the general population which are not occupationally exposed. It is necessary to refer to these values in order to compare the data obtained through biological monitoring programmes in workers and in groups of the general population which are presumed to be exposed. The most essential aspects for identifying reference values for toxic metals, using a rigorous methodology, are taken into consideration and in particular, the requisites needed for identifying the subjects which must be included in the reference groups are also examined. The modalities for using reference values for individual subjects as well as for groups are then discussed and the main points of research which must be faced in the near future regarding reference values are highlighted. PMID- 1641629 TI - Tentative reference values for some elements in broncho-alveolar lavage fluid. AB - The concentrations of Fe, Mn, Pb and Cr have been determined in broncho-alveolar lavage (BAL) fluid of 25 subjects without occupational or abnormal environmental exposure to metals, using the AAS method. The numerous factors which can interfere with the results in pre-analytical and in analytical phases are stressed. Metals concentrations in BAL are expressed in micrograms/l. They were not correlated with the volume of fluid recovered, the total cells, alveolar macrophages and erythrocytes. The results were not modified by stratification considering age and sex. Iron concentrations were higher than others, probably due to higher environmental exposure and partly to its essential role in humans. The diagnostic significance of element determination in BAL fluid and the relationship with exposure and lung load is discussed. PMID- 1641630 TI - Cadmium in blood and urine after cessation of exposure. AB - A plant for the synthesis and packaging of cadmium oxide was operated for 32 months (1982-84) in a small chemical factory producing zinc and copper oxide. The cumulative exposure of 6 workers was from 12 to 190 days. Five years after cessation of exposure the blood cadmium levels in the exposed were, on average, 4 10 times higher than those of a reference group and the urinary cadmium levels were 1-6-times higher. In view of the long half-life of cadmium in the human body, the choice of normal reference values requires particular care since brief and sometimes forgotten exposures to cadmium may be a confounding factor to set reference values. PMID- 1641631 TI - The microdose problem and the most commonly used metals. AB - On the basis of recent research a relationship may exist between microexposure to metals and certain diseases (e.g. neurological and cardiovascular diseases) which occur in the later stages of life. This fact must be kept firmly in mind in view of the implications for the quality of health, considering the increase in average life expectancy. Moreover, it will be necessary to re-identify the critical organ for each metal, bearing in mind that the effects are altered in low level exposure conditions. PMID- 1641632 TI - Is hypertension a confounding factor in the assessment of blood lead reference values? AB - In order to evaluate whether hypertension can be considered as a confounding factor in the setting up of reference values for blood lead, we examined the results of a cross sectional study which evaluated the relationship between lead in blood and hypertension in a sample of 254 males and 271 females of a general population not occupationally exposed to lead. The statistical analysis and in particular the multiple logistic regression showed that, even if some well-known confounding factors such as age, sex, overweight, smoking and alcohol are taken into account, blood lead levels are well correlated with hypertension. The results suggest that even modest lead absorption is able to influence the probability of being hypertensive. The relationship between blood lead and hypertension and their relationship with the main confounding factors involved in the determination of reference values of metals in blood are discussed. PMID- 1641633 TI - Reference values of tests for the assessment of mutagenic activity. AB - The determination of mutagenic activity in biological media aims at detecting the exposure to mutagenic chemicals, or to chemicals transformed by the organism into mutagenic metabolites. Mutagenic activity is detected by various short-term tests which rely upon the interaction of the chemical with the DNA of, bacteria, Drosophila or mammalian cells. The urinary fluctuation test has been particularly useful in determining mutagenic activity in the urine of subjects exposed to low concentrations of suspected genotoxic chemicals. The assay procedure itself is relatively simple, the data, however, should be carefully evaluated in relation to the attributes of the donor, bearing in mind the confounding variables related to life-style, diet, occupation and drug intake. PMID- 1641634 TI - Reference values for chromosome aberrations in human lymphocytes as indicators of genotoxic effects. AB - Increased chromosome aberrations (CA) in human cultured lymphocytes are an accepted indicator of early biological effects of exposure to genotoxic agents, which has also been investigated, with conflicting results, in several groups of subjects occupationally exposed to metals known or suspected to be carcinogenic. One of the problems with this indicator is the lack of universally accepted reference values. Difficulty in establishing absolute reference values for CA depends on individual variability in the reference groups (due to several environmental and genetic confounding factors) and on methodological variants at the different stages of the test (culture methods, scoring, classification and reporting of CA). Therefore, at present, CA studies in exposed groups should include proper 'control' groups, matched for the known confounders, investigated in the same laboratory, with the same methods in order to minimize factors of variation. The results of the studies should be statistically compared and evaluated mainly on a group basis. PMID- 1641635 TI - Statistical aspects of the estimation of reference limits. AB - This paper deals with some basic statistical issues arising from biological monitoring. Data description, Gaussianity tests, outlier identification, parametric and non-parametric estimates of fractiles and their standard errors, and parametric estimate of the one tail upper side tolerance interval are treated and exemplified using two data sets. Sample size and power determination are considered in terms of the cut-off point of the diagnostic quantitative test. PMID- 1641636 TI - The ICOH and IUPAC international programme for establishing reference values of metals. AB - In cooperation with the ICOH Scientific Committee on the Toxicology of metals and IUPAC Commission on Toxicology, we have developed evaluation criteria for derivation of reference values for metal concentrations in human tissues and fluids. In a first attempt to illustrate how these criteria may be used, tentative reference values for mercury in human blood were derived. For persons who do not eat fish, a mean value of 10 mumol/1 (2 micrograms/1) was suggested. It was pointed out, however, that this value was based on information that did not meet the desired quality requirements, which, unfortunately were not met by any of the published reports. PMID- 1641637 TI - Non-parametric age related centile curves for blood lead levels in blood donors from northern Italy. AB - Healy's non-parametric method, originally applied to growth data, provides an efficient and flexible tool for computing smoothed centile curves. We used this procedure to calculate reference curves for blood lead levels. A sample of 402 blood donors living in Brescia and its surrounding area was used as a reference population. No exclusion criteria but occupational exposure to lead were adopted. The comparison between the reference values obtained with Healy's procedure and the tolerance limits, based on the normal approximation, computed within age strata is discussed. PMID- 1641638 TI - Criteria for the definition of reference values for toxic metals. AB - Two types of selection are used to identify subjects who make up reference groups: 'a posteriori' selection starting from a large number of subjects who are then subsequently selected and 'a priori' selection wherein the group to be examined is defined on the basis of preestablished criteria. The main variability factors are biological and those depending on the modalities of selection of groups and determination of the analysis. The nature of the element is also particularly important, i.e. whether an essential element must be considered only a micropollutant or whether it should be considered essential and at the same time a micropollutant. In addition two other factors which play an important role are the temporo-spatial modifications induced by natural or anthropogenic phenomena which influence the modality and degree of exposure in man. Two criteria are generally used in the production of reference groups: exclusion/inclusion and partitioning criteria. While in clinical chemistry the health status represents an important exclusion factor, in the case of metals, the environmental conditions and the function of organs and apparatuses involved in the toxicokinetics of metals can be considered as main criteria. All the other variables such as sex, age, life-style are partitioning criteria and enable us to obtain reference values for more and more homogeneous subgroups. PMID- 1641639 TI - Trace element reference values in tissues from inhabitants of the European Community. II. Examples of strategy adopted and trace element analysis of blood, lymph nodes and cerebrospinal fluid of Italian subjects. AB - The EURO TERVIHT (Trace Element Reference Values in Human Tissues), recently initiated, aims to establish and compare trace metal reference values in inhabitants from the different EC countries. The project anticipates international cooperation of specialized chemical and toxicological laboratories in Western Europe. In order to overcome the well known and intolerable high fluctuation in published trace metal concentrations in body fluids and tissues, which are mostly due to poor analysis, this paper gives recommendations and strategies for approaching 'background' values measurement practised in the EURO TERVIHT. The focus of the paper is more on quality rather than on quantity of data with particular aspects: (i) well-described protocol for the selection/composition of reference groups (extended epidemiological data plus clinical status); (ii) numerous pre-analytical factors, among which are of paramount importance are ultraclean laboratory air, container material, storage conditions at -20 degrees C; (iii) statistical treatment of the data and the expression of the analytical results (use of refined statistical analysis such as the Lilliefors test to define the type of distribution, normal or log-normal). Results reported here concern the determination of trace elements in whole blood of more than 350 Italian subjects which allowed the proposal of 'reference values' for 12 elements. In lymph nodes and cerebrospinal (CSF) the degree of information acquired is only sufficient to suggest 'indicative' of 'informative' values. PMID- 1641640 TI - Trace element reference values in tissues from inhabitants of the European Community. III. The control of preanalytical factors in the biomonitoring of trace elements in biological fluids. AB - In the context of a programme concerning the determination of trace elements in body fluids and tissues to establish trace element reference values, research has been undertaken on the control of preanalytical factors in order to develop sufficiently accurate and precise guidelines to be applied in routine work by using techniques such as graphite furnace atomic absorption spectroscopy (GFAAS). Aspects investigated are related to the risk of contamination during blood collection and the use of anticoagulants; the risk of losses during storage and freeze-drying as well as the possible risk of contamination arising from trace elements in airborne particulates of the laboratory environment. For the analysis of Al, Ba, Cd, Co, Cr, Mn, Mo, Ni, Sb, W, V and Zn in blood, Teflon cannula is the method of choice. The anticoagulants do not introduce disturbing contaminations of Rb, Se, Zn, while contaminations were observed for Co, Cr, Mn. Radiotracers in 'metabolized form' (radiolabelled rat or rabbit tissues from animals administered with radioisotopes) show that samples stored for 1 month at 20 degrees C have no significant trace metal losses. Strict ambient air quality standard has to be respected (continuous monitoring) due to the possibility of element contaminations inside the laboratory. The use of matrix modifiers could represent a toxicological risk to the operators. Critical factors should be considered ('metal sheets') for each element in each matrix. For instance 27 factors for Cr in serum have been suggested. PMID- 1641641 TI - Reference values for early markers of renal damage. AB - In addition to the difficulties related to the definition of a reference population and hence of reference limits, special methodological problems have to be dealt with when early markers of renal damage are applied to monitor groups at risk. The urinary excretion of both high and low molecular weight proteins, as measured by sensitive immunoassays, is routinely applied in health surveillance programmes aimed at preventing the occurrence of adverse renal effects resulting from exposure to nephrotoxic chemicals, among which are several metals. Owing to the large intra-individual variability experimentally demonstrated for all indicators of renal impairment, carefully standardized sampling conditions must be adopted. At the individual level, repeated measurements should be performed before a diagnosis of renal disease or dysfunction is established. In fact, several physiological conditions may account for transient changes in renal function, leading to measured levels greatly exceeding reference limits. PMID- 1641642 TI - Inaccuracy quality control in the monitoring of trace metal concentrations in biological fluids. AB - Quality assurance in trace element analysis requires continual surveillance of the accuracy and precision of results. A review of difficulties encountered in performing quality control programs of trace metal analysis in biological fluids is presented. Examples to clarify the inadequacy of available biological reference materials for quality control in biological monitoring of environmental and occupational low level exposure to metals are reported. PMID- 1641643 TI - Exposure to metals that have recently come into use. AB - The possibility of deriving normal biological values for some rare metals is investigated. The metals under study are gallium, germanium, indium, niobium and tellurium, i.e. a group of metals with increasing utilization in the electronics industry. So far some data are unavailable for some of the elements, e.g. daily intake, oral absorption and half-life time for gallium, and body burden for gallium and germanium. Reliable values of blood concentration are available only for gallium, niobium and tellurium. The problem related to a proposed urinary biological limit value for tellurium is also discussed. PMID- 1641644 TI - Tentative reference values for gold, silver and platinum: literature data analysis. AB - Data available on biologic fluid content of therapeutic metals are uneven for silver, gold and platinum respectively. Tentative reference values may be proposed on the basis of the most representative studies for silver and gold. For silver it is suggested that the variability in normal subjects could range up to 10 micrograms/l in whole blood and up to 1 microgram/l in urine. For gold 0.5 microgram/l can be considered the upper limit for both whole blood and urine. For platinum there is no indication that concentration in either blood or urine could reach detectable amounts in normal subjects. PMID- 1641645 TI - Plasma selenium levels of the general population of an area in northern Italy. AB - Plasma selenium (Se) levels of 293 subjects (160 males and 133 females) living in Desio (a small town near Milan) were determined. Analyses were performed by graphite-furnace atomic absorption spectrophotometry with Zeeman background correction. Plasma samples were not subjected to any treatment before analysis and serum samples containing a certified Se content were used as reference materials to control the quality of the analytical determinations. Plasma Se levels were found to be distributed normally with an average value of 118.8 micrograms/l and a S.D. of 27.2 (95% of the subjects lie between 64.4 and 173.2 micrograms/l). No statistically significant difference was found between males and females, and no correlation was found between plasma Se levels and age or smoking habits. PMID- 1641646 TI - Clams as pollution bioindicators in Kuwait's marine environment: metal accumulation and depuration. AB - This study has developed and verified clam transplantation for marine pollution monitoring in Kuwait and has assessed its reliability for monitoring pollution by heavy metals through laboratory and field transplantation experiments. In field experiments, live specimens of the clam Circenita callipyga were transplanted, either suspended in seawater or buried in sand, to 11 coastal sites in Kuwait; subsamples of transplanted clams were recovered at intervals over a 6-month period. In laboratory experiments, heavy metal accumulation for 36 days and depuration (body's release of pollutants) for 60 days in small and big clams were investigated. Clams subsampled in laboratory and field experiments were analyzed for Hg, Cu, V, Cd and Pb. Results showed the ability of clams to survive under the transplantation conditions. Accumulation of biofouling materials was a problem at only two transplantation sites and was overcome by periodic cleaning. Statistical analysis of laboratory experimental data showed significant accumulation of all test metals and significant depuration of Hg, Cu, V and Cd. Rates of metal accumulation and depuration differed in relation to clam size class. Field experiments indicated statistically significant increases in Hg and Cu concentrations in the transplanted clams at most stations, no change in Cd concentrations and an increase or, occasionally, a decrease in V and Pb concentrations. PMID- 1641647 TI - Bioaccumulation of 137Cs and 60Co by a tropical marine teleost Epinephelus sp. AB - As part of a project on the behaviour of radionuclides released by the Angra Nuclear Power Station in the marine environment, laboratory experiments were performed to study cesium and cobalt accumulation by juvenile groupers (Epinephelus sp.). The fishes were kept in aquariums equipped with gravel-bed filters spiked with 60Co (150 KBq/l) and 137Cs (75 KBq/l). Uptake was only via water since the fishes received only non-radioactive food during the 4 months of experiment. Cesium accumulation in muscle was higher than in any other organ, reaching concentration factors (CFs) of 5 (fresh weight basis). Cobalt, in contrast, was concentrated mostly in the liver, gut and skin and scales. Cobalt CF in muscle tissue was 8 x 10(-2), lower than any previously reported figure. Chromatographic analysis of the water at the beginning and end of the experiment showed that cobalt had been completely converted from 60CoCl2 to non-cationic forms, most probably through complexation with organic ligands, mediated by the intense microbial activity of the filter bed. This conversion apparently enhanced cobalt bioavailability since a second experiment performed with this aged seawater yielded CFs for muscle tissue higher by a factor of 2.5. PMID- 1641648 TI - Mechanism of action of hydroxyurea. AB - Hydroxyurea is well absorbed after oral administration, converted to a free radical nitroxide in vivo, and transported by diffusion into cells where it quenches the tyrosyl free radical at the active site of the M2 protein subunit of ribonucleotide reductase, inactivating the enzyme. The entire replitase complex, including ribonucleotide reductase, is inactivated and DNA synthesis is selectively inhibited, producing cell death in S phase and synchronization of the fraction of cells that survive. Repair of DNA damaged by chemicals or irradiation is also inhibited by hydroxyurea, offering potential synergy between hydroxyurea and radiation or alkylating agents. Hydroxyurea renders cells sensitive to bleomycin because the quenched tyrosyl free radical no longer stabilizes the adjacent iron center, making it more susceptible to the chelating properties of bleomycin, which then produces active oxygen. Synergy has also been observed between hydroxyurea and a number of other chemotherapeutic agents, including cytarabine and etoposide. Recently, two new effects of hydroxyurea have been observed: hydroxyurea increases the level of fetal hemoglobin, leading to a reduction in the incidence of vasoocclusive crises in sickle cell anemia, and hydroxyurea selectively reduces the level of episomal DNA and thus potentially may reduce drug resistance associated with duplicated genes retained as episomes. Further exploration of the efficacy of hydroxyurea in combination with other therapeutic agents is warranted. PMID- 1641649 TI - Current advances in hydroxyurea therapy. PMID- 1641650 TI - Cytotoxic synergy of cisplatin with concurrent hydroxyurea and cytarabine: summary of an in vitro model and initial clinical pilot experience. AB - Cytarabine and hydroxyurea in combination are known to inhibit the DNA excision repair system. Given this system is responsible for repair of cisplatin-DNA adducts, we hypothesized that combining cytarabine, hydroxyurea, and cisplatin in an appropriate schedule might inhibit adduct repair, increase the number of DNA lesions, and produce synergistic cell kill. In vitro experiments using clinically achievable doses and schedules of these antimetabolites demonstrated cytotoxic synergy with the three-drug combination, but little or no such synergy with either antimetabolite plus cisplatin. The inclusion of hydroxyurea was necessary to achieve maximum synergy. Increased levels and persistence of cisplatin-induced DNA interstrand cross-links were observed, suggesting repair inhibition may have occurred. The dose of cisplatin required to inhibit colony formation by 90% was reduced approximately one third, even after normalization for the cytotoxic component(s) of hydroxyurea, cytarabine, and hydroxyurea plus cytarabine. Using one of the two optimal in vitro schedules for the three-drug combination, we performed a clinical pilot study in two patient cohorts (with and without prior systemic therapy). Administration of the program was feasible, and resulted in dose-limiting thrombocytopenia only in the cohort with prior chemotherapy. Azotemia was treatment-limiting in responding patients. Responses were observed in patients with a variety of solid tumors, including several patients who had previously failed cisplatin therapy. Modifications of this program are discussed, which have, to date, significantly decreased the toxicity concerns raised by the first trial. Phase II trials are planned in patients with a variety of cisplatin responsive and nonresponsive neoplasms. PMID- 1641651 TI - An overview of the clinical experience with hydroxyurea. AB - In the more than 30 years since hydroxyurea was first evaluated clinically, a number of diverse and unique applications have been identified for its use. Some of these applications were apparent to investigators almost from the beginning, while others are still evolving 3 decades later as a result of ongoing research. An overview of clinical experience with hydroxyurea provides an historical perspective on a period encompassing virtually the entire era in which anticancer chemotherapy has been a recognized discipline. The critical role of the ribonucleotide reductase reaction in the regulation of DNA synthesis makes this enzyme a particularly important target site for antineoplastic therapy. The sustained interest in hydroxyurea, however, has been the result of careful clinical observations as well as basic laboratory studies, which support current attempts to identify additional uses for the drug. This overview describes the clinical development of hydroxyurea, discusses current indications, and briefly describes areas of ongoing research that may expand the clinical indications for hydroxyurea. PMID- 1641652 TI - High-dose hydroxyurea in autologous bone marrow transplantation: a promising "new" agent. AB - Hydroxyurea is an antineoplastic drug with a broad spectrum of clinical activity and minimal nonhematopoietic toxicity. It potentiates the cytotoxicity of alkylating agents and topoisomerase II active drugs in vitro and in vivo. It is not susceptible to alkylating agent-specific or multidrug-type resistance. We have therefore added high-dose oral hydroxyurea to widely used autologous bone marrow transplantation combination chemotherapy regimens for large cell lymphoma and metastatic breast cancer. Seventeen patients with primary-refractory or refractory-relapse large cell lymphoma received oral hydroxyurea (1.5 g/m2 every 6 hours for 12 doses) added to carmustine/cyclophosphamide/etoposide (BCV). Twelve patients with metastatic breast cancer received the same dose oral hydroxyurea added to cyclophosphamide and thiotepa. Mucositis severe enough to require parenteral narcotics was seen in over half of the patients, but none required intubation for airway maintenance. A thrombotic thrombocytopenic purpura like hemorrhagic syndrome occurred in six patients and was fatal for three. With the BCV/hydroxyurea regimen, this syndrome was seen with the same frequency as with BCV alone. Death from rapidly progressive disease or toxicity occurred in seven of 29 patients (24%). For patients with 6 months' minimum follow-up, four of 12 (33%) of the metastatic breast cancer patients remain in complete response (median follow-up, 15 months), and four of 17 (24%) refractory large cell lymphoma patients remain in complete response (median follow-up, 10 months). High dose hydroxyurea may increase the effectiveness of standard autologous bone marrow transplantation regimens without substantially increasing toxicity. PMID- 1641653 TI - The evolution of hydroxyurea therapy in chronic myelogenous leukemia. AB - The evolution of hydroxyurea as a chemotherapeutic agent has been unique. Hydroxyurea inhibits synthesis of DNA, has antitumor activity, and is myelosuppressive. It has attained a significant role in the management of chronic myelogenous leukemia. A nonrandomized comparison of busulfan and hydroxyurea concluded that hydroxyurea was the preferable agent in the treatment of chronic myelogenous leukemia and was associated with less life-threatening toxicity. Because of its systemic effects, hydroxyurea is also used in the treatment of polycythemia and psoriasis. PMID- 1641654 TI - A phase II pilot trial of high-dose hydroxyurea in chronic myelogenous leukemia. AB - Suppression or eradication of the Philadelphia (Ph1) chromosome has been a major goal in the therapy of chronic myelogenous leukemia (CML). Variable levels of Ph1 chromosome negativity have been achieved using interferon-alfa, busulfan, combination chemotherapy, and allogeneic bone marrow transplantation. This study evaluated the effect of achieving a predetermined level of myelosuppression using hydroxyurea on bone marrow cytogenetics in CML. Fourteen patients with chronic phase CML received 25 cycles of therapy. Fourteen of the 25 cycles were associated with cytogenetic responses consisting of 25% or more Ph1 negative metaphases (range, 25% to 100%). Nine of the responses consisted of 50% or greater Ph1 negative metaphases. Toxicity was exclusively due to consequences of myelosuppression, including febrile neutropenia and thrombocytopenia. In chronic phase CML, hydroxyurea induces cytogenetic responses with tolerable toxicity and is an attractive agent for further study as a component of treatment strategies aimed at eradicating the Ph1 + population in CML. PMID- 1641655 TI - The place of hydroxyurea in the treatment of primary brain tumors. AB - Hydroxyurea has been used since the early 1970s to potentiate the effects of radiation in the treatment of primary gliomas. In the only randomized study, a statistically significant increase in time to tumor progression for glioblastoma patients was noted for those receiving hydroxyurea. In other studies, hydroxyurea has been used as a cell-cycle phase-specific agent to improve survival in patients with recurrent gliomas and, in combination with 5-fluorouracil, to increase cell kill and as a potential DNA polymerase inhibitor. Other protocols have used hydroxyurea during radiation therapy in medulloblastoma and in combination chemotherapy for metastatic brain tumors as well. While widely used in the treatment of primary and secondary brain tumors, hydroxyurea trials usually have not been randomized or otherwise controlled; most have been nonrandomized, phase II activity studies. With the conclusion of some current trials, it is conceivable that the use of hydroxyurea may be more clearly defined in the treatment of tumors affecting the nervous system. PMID- 1641656 TI - Radiosensitization and cell kinetics: clinical implications for S-phase-specific radiosensitizers. AB - Rapid repopulation of tumor cells during conventional radiation therapy has been recently recognized as a factor that might significantly impair tumor response in several different tumor sites. One clinical strategy to overcome rapid tumor proliferation is to use S-phase-specific radiosensitizers such as hydroxyurea and the halopyrimidines 5-iododeoxyuridine (IUDR), 5-bromo-2'-deoxyuridine (BUDR), 5 fluoro-2'-deoxy-beta-uridine (FUDR), and 5-fluorouracil (5-FU). Indeed, several recent clinical trials have shown the positive antiproliferative effects of these radiosensitizers in various human tumors. In spite of this resurgence of clinical interest, the basic mechanism(s) of radiosensitization is not clearly understood. Although the halopyrimidines have similar biochemical pathways involving two key regulatory enzymes, thymidine kinase and thymidylate synthase, it appears that DNA-incorporation is important for radiosensitization by BUDR and IUDR but not for FUDR or 5-FU. Recent laboratory data suggest that biochemical modulation of the key regulatory enzymes can result in selective tumor radiosensitization with halopyrimidines. Hydroxyurea, like 5-FU, sensitizes cells when present prior to and following irradiation; this interaction may be related to cell synchronization as well as altered DNA damage repair. Exploiting differences in cell proliferation and cellular metabolism of these S-phase-specific radiosensitizers in tumors and normal tissues will be a major focus of clinical research in human tumor radiosensitization over the next few years. PMID- 1641657 TI - Experience with hydroxyurea as a radiosensitizer in carcinoma of the cervix. AB - Since 1968, hydroxyurea has been used as a radiosensitizer in combination modality treatments for carcinoma of the cervix. The drug has shown an advantage over placebo in several randomized trials. Although hydroxyurea is given orally on an outpatient basis, it has not gained widespread acceptance. Previous reports are reviewed and possible future uses are discussed. PMID- 1641658 TI - Hydroxyurea with concomitant radiotherapy for locally advanced head and neck cancer. AB - Hydroxyurea is an active single agent in squamous cell cancer of the head and neck. It has been used clinically, most frequently as a radiation-enhancing agent with concomitant radiotherapy. Pilot trials testing hydroxyurea in this setting reported encouraging results. Two randomized trials have been conducted with inconclusive results, possibly relating to study cohort size and short period of follow-up. More recently, hydroxyurea has been investigated with 5-fluorouracil and concomitant radiotherapy. A sound theoretic rationale can be made for this approach and data derived from a phase I/II study are presented. These support the further investigation of this regimen. PMID- 1641659 TI - Laboratory and clinical studies of biochemical modulation by hydroxyurea. AB - Hydroxyurea is a potent inhibitor of the enzyme ribonucleotide reductase. Due to its effects on cellular deoxyribonucleotide pools, hydroxyurea can modulate the activity of several pyrimidine and purine antimetabolites. As an inhibitor of DNA repair, it can potentially interact with DNA-damaging agents such as alkylating agents or inhibitors of topoisomerase II. Both cytokinetic and biochemical interactions occur between hydroxyurea and cytarabine (ara-C), which account for their synergistic cytotoxicity. Inhibition of ribonucleotide reductase by hydroxyurea depletes cellular deoxycytidine triphosphate pools, thereby enhancing ara-C uptake and phosphorylation to ara-C triphosphate. In a phase II clinical trial, the combination of hydroxyurea and ara-C produced a 43% response rate in patients with refractory malignant lymphoma. Studies in murine leukemia models have demonstrated therapeutic synergy when hydroxyurea is combined with fluoropyrimidines. High levels of deoxyuridine monophosphate that have been associated with resistance to 5-fluorouracil can be suppressed by hydroxyurea, leading to greater inhibition of thymidylate synthase. Despite the strong biochemical rationale for the use of hydroxyurea and 5-fluorouracil in combination, few clinical trials have been conducted thus far. Antimetabolites and topoisomerase II inhibitors have also been shown to be synergistic in vitro. Hydroxyurea has been shown to enhance the formation of DNA strand breaks produced by amsacrine and to produce synergistic cytotoxicity with etoposide. A phase I clinical trial of these drugs has demonstrated bone marrow suppression to be the major toxicity of the combination. In summary, hydroxyurea has been shown to undergo cytokinetic and biochemical interactions with a number of established antitumor agents. Clinical trials of hydroxyurea in combination with these agents have identified doses and schedules of administration that produce acceptable levels of clinical toxicity and appear feasible for further testing. PMID- 1641660 TI - Treatment of colon cancer based on biochemical modulation of fluoropyrimidines by hydroxyurea. AB - Preclinical studies have indicated that hydroxyurea leads to enhancement of 5 fluorouracil (5-FU) activity when given after 5-FU. This is presumably due to hydroxyurea's actions resulting in maintaining low levels of deoxyuridine monophosphate pools. The combination of hydroxyurea and 5-FU has been tested in several inconclusive clinical trials in patients with advanced colorectal cancer. However, pharmacodynamic studies have been lacking, and the schedules tested have not usually tried to follow preclinical findings. With the current renewed interest in 5-FU, a role for hydroxyurea as part of its biochemical modulation is worthy of further study. PMID- 1641661 TI - Enhancement of the loss of multiple drug resistance by hydroxyurea. AB - Gene amplification is one mechanism whereby tumor cells can become resistant to antineoplastic agents. Unstably amplified genes occur either on submicroscopic circular pieces of extrachromosomal DNA called episomes or on small acentric chromosomes called double minutes. Double minutes are frequently associated with cells containing amplified drug-resistance genes. Human epidermoid carcinoma KBV1 cells contain unstably amplified mdr1 genes and overexpress P glycoprotein, resulting in decreased intracellular drug accumulation. In this cell line, a nonlethal concentration of hydroxyurea accelerated the rate of loss of vinblastine resistance once vinblastine had been removed from the culture medium. After removal of vinblastine, KBV1 cells exposed to hydroxyurea for the time required to complete 12 cell doublings accumulated more vinblastine than control cells grown in the absence of hydroxyurea. In contrast, hydroxyurea had no effect on vinblastine sensitivity and accumulation in parental drug-sensitive KB-3-1 cells. Hydroxyurea also had no effect on sensitivity to cisplatin in cisplatin resistant human ovarian carcinoma 2008/C13* cells, indicating that hydroxyurea's effect on drug sensitivity was specific for a drug-resistance phenotype associated with unstably amplified drug-resistance genes. These results indicate that, after removing selective pressure, hydroxyurea accelerates loss of resistance to vinblastine and increases accumulation of vinblastine in KBV1 cells, presumably by accelerating loss of amplified mdr1 genes and thus P glycoprotein. PMID- 1641662 TI - The role of tissue factor pathway inhibitor in a revised coagulation cascade. PMID- 1641663 TI - The tissue factor pathway of blood coagulation. PMID- 1641664 TI - The roles of fibrinogen and fibrin in hemostasis and thrombosis. AB - Proteolytic conversion of fibrinogen to fibrin results in self-assembly to form a clot matrix that subsequently becomes cross-linked by fXIIIa to form the main structural element of the thrombus in vivo. Fibrin formation and assembly lead to new properties that regulate the rate and extent of clotting, cross-linking, and fibrinolysis. These are brought about by the ability of fibrin (1) to bind thrombin at a nonsubstrate site, thus limiting its diffusability but at the same time preserving its catalytic potential; (2) to bind fXIII, regulate its activation to fXIIIa, and limit further activation of fXIII once fibrin cross linking has occurred; and (3) to bind alpha 2-PI, t-PA, and plasminogen and regulate the initiation and propagation of fibrinolysis. Fibrinogen and fibrin contain several potential platelet binding sites that interact with platelet GPIIb/IIIa receptors, and thus promote their participation in the hemostatic process. Additional, less well-defined interactions, not covered in detail here, such as those between fibrinogen or fibrin and other plasma proteins, cells, or tissue matrix components, suggest other functions that, along with those detailed above, will further define its multiple roles in modulating hemostasis, inflammation, and the wound healing process. PMID- 1641665 TI - Factor XI: a renaissance. PMID- 1641666 TI - The role of leukocytes in the activation of blood coagulation. PMID- 1641667 TI - Surface-dependent hemostasis. PMID- 1641668 TI - The cultural logic of Indian medicine: prognosis and etiology in Rajasthani popular therapeutics. AB - This paper considers certain ways of describing and treating sickness in rural Rajasthan, and the representations of sickness and of the body on which they are based. Two indigenous medical or 'ethnomedical' perspectives on illness and its treatment emerge from the analysis of ethnographic material collected during field research in northern India. In the first part of the paper various characterizations of South Asian medicine are discussed, and I suggest that Western preconceptions about the nature and purpose of 'medicine' itself has led one of these perspectives to be highlighted in anthropological considerations at the expense of the other. A further dimension of ethnomedicine emerges through discussions of local therapeutic rituals and discourses about sickness and the body. This consideration of one domain of local therapeutics reveals its underlying cultural logic and highlights ethnomedical formulations that have heretofore been analytically neglected. It does not address the formal or textually based Indian medical traditions to any extent. It is concerned with the cultural construction of sickness and medicine among Hindu lay people and folk healers and employs folkloric material that, though rarely considered in anthropological writings on South Asia, may be fruitful guide to the meanings which sickness has for those experiencing and treating it. PMID- 1641669 TI - What can information systems do for primary health care? An international perspective. AB - The reform of health information systems has been made a priority by health managers, public health specialists and technocrats. While each of these groups has promised major benefits from improvements in information systems, insufficient attention has been paid to the limitations placed upon the theoretical possibilities of information technology by the characteristics of the health system of which the information system is but a part. Managers anticipate improved efficiency and rational allocation of resources, but rational decision making does not automatically follow from improvements in information. Epidemiologists and public health specialists seek more effective and equitable health systems but methodological problems and the expense of many conventional epidemiological approaches continue to limit the usefulness of disease surveillance, programme monitoring and evaluation. Both managers and epidemiologists are confronted with the conflicts which arise in seeking to create locally sensitive information systems within centralised health systems. Technocrats see microcomputers as essential for information systems to be truly effective and as a means of liberating health workers from the drudgery of form filling. However, the rate of organisational evolution in the health system has not kept pace with the rapid development of information technology. There are good prospects for considerable health gain to be wrought from reforms in health information systems but to realise these it is necessary that this process be 'action-led' rather than, as is conventional, 'data-led'. The latter approach sees data as the end in itself; the 'action-led' approach, in contrast, regards information as needs to interventions with a focus on how information will influence decisions. For improvements in information to result in improved health, strategies must be adopted which will ensure that information routinely informs decisions and is seen as a means to the end of improving health. PMID- 1641670 TI - Community-based HIV/AIDS research--whither community participation? Unsolved problems in a research programme in rural Uganda. AB - Involvement of the study community in research on HIV/AIDS has presented the MRC/UVRI programme in rural Uganda with a multi-layered challenge. A typology developed in agricultural research which defines different levels of community participation in research is described where participation may be at 'contract', 'consultative', 'collaborative' and 'collegiate' level (each level indicating an increasing degree of community participation). Community involvement in the MRC/UVRI Programme is then outlined and the typology applied. It is shown that the majority of community participation in the Programme is at the contract level since the nature of the research programme as a 'foreign imposition' with 'foreign goals' has precluded the involvement of the community in much of the policy development and research planning. However, it is noted that as the Programme becomes more established in the area community influence grows and signs of community impact on policy and increased research inputs are beginning to be seen. The question is raised as to whether it is realistic to expect that externally imposed health research, particularly on sensitive topics, can ever be truly community participatory research. PMID- 1641671 TI - Quantitative and qualitative approaches to the evaluation of the medical dialogue. AB - Increasing availability of audio and videotape of medical encounters has drawn the attention of researchers from diverse disciplines and perspectives. Unfortunately, the result has more frequently been interdisciplinary competition than collaboration. Most striking are the differences in approach between researchers applying qualitative and quantitative methods. Advocates of each of these methods have not only argued their own relative merits, but have maintained unusually critical and intellectually isolated positions. The purpose of this paper is to demonstrate that the paradigmatic perspective which promotes mutual exclusivity is in error. We present several examples of research findings which demonstrate the rich potential for cross-method research. Examples have been taken from the areas of most fruitful qualitative and quantitative research- information gathering, patient disclosure, and information-giving. PMID- 1641672 TI - Yolmo aesthetics of body, health and 'soul loss'. AB - To date, little attention has been paid to the cultural philosophies of experience which shape human behavior. The present paper contends that culturally constituted 'aesthetics' of everyday life underlies moments of health, illness and healing among Yolmo Sherpa of Helambu, Nepal. The author examines cultural understandings of bodily and social experience to show how implicit aesthetics- from values of harmony and balance to fears of loss and decay--shape the ways in which Yolmo manage and evaluate their lives and how they construe and experience incidents of 'soul loss.' An analysis of shamanic ritual suggests, in turn, that while themes of imbalance, fragmentation and deficiency haunt the body in illness, healing works to reinstate a visceral sense of harmony, completion and vitality. These values reflect pressing political concerns. The paper concludes that a phenomenology of embodied aesthetics requires an analytic approach distinct from current semiotic, intellectualist, or psychological paradigms. PMID- 1641673 TI - Sexual behaviour related to psycho-social factors in a population of Danish homosexual and bisexual men. AB - An anonymous self-administered questionnaire was distributed to (1) male members of the Danish Gay and Lesbian Association (2) through a gay magazine and (3) to readers of a gay pornographic magazine. For the purpose of this study sexual practices were classified into three categories taking into account the HIV status of the respondent and his partner(s): safe sex (mutual masturbation, sex with condoms, sex without condoms between two HIV-positives), potentially safe sex (oral-genital sex without condoms irrespective of HIV-status, anal-genital sex without condoms between two HIV-negatives), unsafe sex (anal-genital sex without condoms between discordant partners or partners of unknown HIV status). Of the 2058 respondents 29.7% had had unsafe sex in the last 12 months. Multivariate analysis by recursive graphical models showed that sexual practice was directly related (that is conditionally dependent given the rest of the variables) to having a steady partner. Among men without a steady partner sexual practice was also directly related to age and number of partners showing an increase in unsafe sex with number of partners and a decrease with age. Thus of the men 16-19 years of age 43.5% had had unsafe sex irrespective of number of partners vs 5.7% of men older than 44 years and with one to two partners. Sexual practice was not directly related to any other demographic or psychosocial factor in the study. The adopted classification of sexual practice preclude that the high occurrence of unsafe sex could be explained by unsafe sex taking place among partners of concordant HIV status. The results emphasize the need for further preventive efforts to reduce transmission of HIV among homosexual men. PMID- 1641674 TI - Development and validation of the PCQ: a questionnaire to measure the psychological consequences of screening mammography. AB - We have developed a reliable and valid questionnaire to measure the psychological consequences of screening mammography. The questionnaire measures the effect of screening on an individual's functioning on emotional, social, and physical life domains. Content validity was ensured by extensive review of the relevant literature, discussion with professionals and interviews with attenders at a pilot Breast X-ray Screening Program in Melbourne, Australia. Discriminant validity was assessed by having expert judges sort items into dimensions which they appeared to be measuring. Acceptable levels of concordance (above 80%) with a priori classifications were found. Concurrent validity was demonstrated by comparison of subscale scores of 53 attenders at the Breast X-ray Program with an independent interview assessment of dysfunction on each of the emotional, social and physical dimensions. There was over 79% agreement between interview scores and questionnaire scores for each dimension. Construct validity was confirmed by showing that subscale scores varied in predicted ways. For women who were recalled for further investigation, scores on each subscale measuring negative consequences, were higher at the recall clinic than at screening clinic (emotional: t = -7.28; df = 70; P less than 0.001; physical: t = -2.53; df = 70; P = 0.014; social: t = -2.49; df = 70; P = 0.015). The internal consistency of all subscales was found to be acceptable. This questionnaire is potentially useful for assessing the psychological consequences of the screening process and should have wide application. PMID- 1641675 TI - The impact of road construction on the spatial characteristics of hospital utilization in the Meru district of Kenya. AB - This paper examines the effect of road construction on the catchment area of a church hospital. It is hypothesized that the new road will reduce the spatial and travel cost relationships for the hospital's patients. Analysis of the data suggests that the space-reducing effect of the new road is more important than its effect on travel costs. Reductions in the cost of travel have not significantly changed the spatial pattern of in-patient utilization. In contrast, out-patients show the hospital is attracting patients from further afield, though this involves a similar expenditure on fares to that prior to road construction. Institutional barriers, particularly the economic barrier of fee-paying treatment, are found to be the main explanation for this finding. The high cost of medical treatment also goes some way towards explaining the low level of child treatment apparent in the patient records. PMID- 1641676 TI - Determinants of perceived health status of medical outpatients. AB - The aim of this study was to examine the relative contributions made by medical morbidity, psychiatric disorder, functional status, and hypochondriacal attitudes to medical patients' opinions of their overall health status. The study was conducted in the general medical clinic of a large academic teaching hospital. Consecutive clinic visitors on randomly selected days were screened with a hypochondriasis self-report questionnaire, since the overall project was designed as a study of hypochondriasis. A random sample of the patients below a pre established cutoff (n = 100), along with all those exceeding the cutoff (n = 88), returned to undergo a research battery. For this analysis, a representative sample of the entire clinic was reconstituted by weighting the data from patients above and below the screening cutoff in proportion to their prevalence in the clinic. Measures of psychiatric disorder (the Diagnostic Interview Schedule), personality disorder, functional status and disability, medical morbidity (from physician ratings and medical record audit), and hypochondriacal attitudes were obtained. Patient self-ratings of global health status were significantly correlated with aggregate medical morbidity (r = 0.36; P less than 0.001); psychiatric morbidity (r = 0.48; P less than 0.001); functional disability (for intermediate activities of daily living, r = 0.62; P less than 0.001); hypochondriacal attitudes (r = 0.79; P less than 0.001); and with the tendency to somatize (r = 0.77; P less than 0.001). Using multiple regression analysis, the most powerful correlates of perceived global health were hypochondriasis, somatization and disability (model R2 = 0.762).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641677 TI - Communicative styles and adaptations in physician-parent consultations. AB - This investigation compares the degree to which personal and interactive factors respectively account for variation in patterns of physician-parent communicative exchange. The analysis of audiorecordings of 115 pediatric consultations revealed several notable findings: (a) individual physicians differed in the degree to which each provided information, issued directives, exhibited positive socioemotional behavior, and engaged in partnership-building, (b) parents who asked more questions and expressed more negative affect (e.g. concerns, frustrations) received more information and directives from physicians, (c) parents who were more affectively expressive elicited a greater number of positive socioemotional comments from doctors, and (d) parents' question-asking and opinion-giving were related to the parents' level of education and the degree to which physicians' engaged in partnership-building. The results of this study suggest that, as are other forms of interpersonal communication, medical consultations are processes of personal and mutual influence that unfold according to the characteristics of the individuals and to interactive processes related to how interactants adapt their communication to one another. PMID- 1641679 TI - Planning health care in South Africa--is there a role for traditional healers? AB - Developing health policies for the 'post-apartheid' era has become an urgent task of the early 1990s in South Africa. A neglected policy issue thus far has been the question of whether traditional healers have a role to play in future health care, and if so what this should be. Rather than developing positions on these questions, this paper sets out the main debates which need the consideration of health care planners. Arguments for and against traditional healers in health care are presented, and alternatives which could be chosen are outlined. Options adopted by countries on South Africa's borders, Zimbabwe, Mozambique and Swaziland are briefly considered. PMID- 1641678 TI - Underreaction to AIDS in Sub-Saharan Africa. AB - In those parts of Sub-Saharan Africa most affected by the HIV/AIDS epidemic both public and private reaction to the seriousness of the epidemic have been less than might have been anticipated. This limited reaction weakens national, community and family responses to the epidemic and also reduces the pressure on international donors to provide adequate support. The paper first examines the reasons for underreaction by governments. These reasons include an assessment that successes will not be easily achieved, a reluctance to give leadership in areas of private sensitivity, an awareness of the fragility of the data base, a persistent feeling that it is a disease of foreign origin with a foreign overreaction to the situation in Africa, and the nature of the disease itself with a long latency period, obscure symptoms and an urban bias. Nevertheless, the paper argues that the more fundamental underreaction, shaping the reactions of governments, is that from the community itself. This arises partly from the demonstration that it is a sexually transmitted disease in societies where the discussion of sexual relations between the generations and the sexes has always been difficult and where new religions have in some societies reinforced older attitudes towards the shame of being discovered to have had illicit relationships. However, the main reasons lie in continuing aspects of the cultures which emphasize the multiple antecedents of misfortune and plural explanations of death, an element of predestination in when death takes place, a concept of good fortune--sometimes arising from or demonstrated by sexual activity--which renders misadventure unlikely, and a courage when facing death which is partly attributable to belief about survival beyond this event. PMID- 1641681 TI - Methodological issues and research strategies in the study of coping with cancer. AB - We explore methodological issues and research strategies and applications in the study of coping with cancer. The major points are addressed within the context of the transactional, or process, model of stress and coping offered by Lazarus and Folkman. Three features of this model are discussed: (a) a focus on what individuals are actually doing and thinking in stressful transactions as opposed to what they usually do or would do; (b) an emphasis on assessing coping behavior in relation to a specific context and; (c) attention to the dynamic nature of coping behavior. We outline each of these three features and discuss its implications for research on coping with cancer; particular attention is given to specific measurement strategies and substantive research questions. We also consider the utility of research on coping with cancer for the design and implementation of coping interventions for individuals with cancer. PMID- 1641680 TI - Suicide and unemployment in Italy: description, analysis and interpretation of recent trends. AB - This paper assesses the relationship between suicide and unemployment in Italy during the period 1977-1987, taking into account variations by gender and region. The first objective of the study is to provide descriptive longitudinal and cross sectional aggregate-level analyses and also trends in individual-level and population risks for suicide in relation to unemployment. Our second objective is to use the Italian data to help discriminate between rival interpretations of the unemployment-suicide link, i.e. the operation of health selection or causal (susceptibility) mechanisms. Evidence for an association between suicide and unemployment among women was not convincing. The annual rate of female unemployment was negatively correlated with the female suicide rate and unrelated to the suicide rate among the unemployed, the relative risk or population attributable risk. Individual-level analyses for each year confirmed that unemployed women were more likely to commit suicide than their employed counterparts, although the overall relative risk was low (1.5) and conference intervals for six of the eleven annual risk ratios included unity (1). Among men, the unemployment rate was positively correlated over time with the suicide rate. However, change in the suicide rate across 18 geographic regions of Italy was unrelated to change in the unemployment rate, a finding which did not appear to be invalidated by a regression to the mean effect. Unemployment was also positively related to the suicide rate among the employed and population attributable risk, but unrelated to the rate among the unemployed or the relative risk. Comparison of suicide rates among the employed and unemployed revealed an excess of suicide among the latter in each year, with an overall relative risk of 3.4. On the basis of this contradictory and inconsistent evidence, we are cautious about offering definitive interpretations concerning the nature of the unemployment-suicide link among men. We conclude by suggesting the need for further individual-level studies using retrospective case-control methods. PMID- 1641682 TI - Patients' choices and perceptions after an invitation to participate in treatment decisions. AB - Previous search indicates that treatment outcomes may be improved if patients perceive greater control over their treatment, but the practical implications of encouraging patients to take more control have not been investigated. The present study investigated responses of 143 patients in a cardiovascular risk management clinic to an invitation to make a decision about their treatment. Subjects' choices of the target behaviour for their behaviour-change treatment were highly predictable from their state of health, reasons for coming to the clinic, what behaviours they were told they were at risk from, and contacts with health workers. The degree of control that subjects reported they had over the decision varied considerably, being negatively related to blood pressure and positively related to the degree of control that subjects believed they had over their health in general. Issues such as time-demands, the practitioner's job satisfaction, and ethical implications of patient participation are discussed. PMID- 1641683 TI - Perceived morbidity and health behaviour in a Dogon community. AB - The episodes of morbidity over a 6 month period were recorded at 179 households comprising 1715 people living in the district of Bandiagara (Mali). This population was subdivided into groups according to their distances from the nearest district health centre and educational services, their scholarization, socio-economic and hygiene levels. The subjects interviewed were asked to report illnesses using their vernacular names, the type of therapy selected, the decision process, the time-lapse between onset and remedial action, the treatment undergone and its effect. Subsequent analysis of the data recorded indicates that the frequency of morbidity episodes is inversely proportionate to the household's level of hygiene. It also appears that factors such as the household's hygienic, socio-economic and educational levels along with the type of illness and its duration, are more decisive when resorting (or not resorting) to treatment than is the proximity factor. This seems particularly true in the case of traditional medicine, chosen even where cosmopolitan resources are available and by people with a relatively high socio-economic, hygienic and educational level. In the specific situation under study this paper indicates those areas for further study with a view to improving public health education. PMID- 1641684 TI - The quality and quantity of social support: stroke recovery as psycho-social transition. AB - The impact of various types and amounts of social support is examined in the context of recovery from first stroke. We conceptualize the rehabilitation process as a psychosocial transition. In a longitudinal design, 44 patients were followed for 6 months following first stroke. Growth-curve analysis (repeated measures MANOVA) was utilized to examine the impact of three types of social support on changes in functional status during recovery. While all three types of support (emotional, instrumental and informational) were shown to be significantly related to recovery of functional capacity, substantial differences were found in the nature of those effects. The impact of social support does not appear during the first month of rehabilitation, indicating the importance of longitudinal designs and longer observation. Patients reporting high level of emotional support showed dramatic improvement despite having the lowest baseline functional status. Instrumental support is most closely related to positive outcomes when provided in moderate amounts. Unlike the other two types, the effect of informational support is mediated by disease severity. PMID- 1641685 TI - Genetic counselor attitudes towards fetal sex identification and selective abortion. AB - Thirty-four prenatal genetic counselors (all but one non-M.D.s) in seven American cities were interviewed on attitudes which might plausibly affect counselor client interchanges. They overwhelmingly endorse both non-directive counseling and the pro-choice ethos which supports a woman's absolute right to abortion in the early stages of pregnancy. However, they also overwhelmingly condemn using prenatal diagnosis for sex selection purposes. Therefore, counselors experience continual stress from clients who evoke the conflict inherent between these two stances. Counselors use a variety of coping mechanisms to minimize this cognitive dissonance. Avoidance through out-referral or invoking institutional policies forbidding prenatal diagnosis for sex selection purposes is a diminishing option and not possible with clients who have or offer a medical indication. More common is the use of psychological coping mechanisms. By elevating the ideals of non directiveness and female autonomy counselors better tolerate client values in conflict with their own. Some redefine the category of 'unwanted pregnancy' to include fetuses of the 'wrong sex'; others redefine the problem as their own ethnocentricism. Empowering counselors to set the protocols they use to screen applicants for prenatal diagnosis would not remove these conflicts. Many counselors believe a ban on releasing fetal sex information while abortion is still a legal option would be organizationally or legally unacceptable, or a violation of patient automony. A complicating factor is that 60% of the counselors interviewed would prefer to know fetal sex in their own pregnancies. Counselors reflect the ambivalence of American society in balancing conflicting social goals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641686 TI - Mother's milk and pseudoscientific breastmilk testing in Pakistan. AB - In urban squatter settlements and rural villages of Pakistan, human breastmilk is regarded as a potential source of destruction as well as of nurturance. Though it is highly valued as crucial for infant survival, it is also thought susceptible to becoming tainted in many ways: by a 'shadow' from the spirit world; by 'evil eye' or black magic due to others' envy; by the effects of a new pregnancy; by the mother's illness or 'weakness'; by her exposure to excessive cold or heat; by her dietary indiscretions. In any of these circumstances, women may stop breastfeeding to prevent illness in the nursing child. Sometimes the stoppage is temporary, brief, and has no serious consequences. When the mother is pregnant, however, it is permanent. Further, if a child is sickly, cries a great deal, has prolonged diarrhea, or seems reluctant to suck, mothers frequently become alarmed and suspect irreversible breastmilk 'poisoning'. In the latter case, a folk healer has traditionally been consulted to test the milk's quality, but in recent years pathology laboratories have increasingly taken on this function in all of the major cities in Pakistan. Not only does the mother stop breastfeeding while the milk is being tested, but often she is unable or unwilling to resume nursing even if the milk is eventually pronounced safe to drink. This manifestation of inappropriate, child-endangering technology has gained acceptance partly because of maternal anxieties heightened by commercially-driven pressures to be 'modern' and partly because of its congruence with traditional ideas surrounding breastmilk, many of which have classical antecedents. PMID- 1641687 TI - Prevalence of smoking in secondary schools in the Greater Accra region of Ghana. AB - Tobacco smoking is fast becoming a public health problem in Ghana and the youth are at a greater risk of becoming victims of it. A survey of nine secondary (high) schools in the Greater Accra Region of Ghana showed that 31.1% of students have smoked before and that 10.3% smoke cigarettes regularly. A significant number of those who had ever smoked (32.6%) came from high socio-economic homes as exemplified by the level of education of the father. Advertising appears to be a factor as to why students start to smoke. Most students (59.4%) appear to know smoking is injurious to health. There is need to motivate secondary school students about not smoking. There is also need to legislate in Ghana to prevent the sale of tobacco products to young people and prohibit smoking in schools and in public places. PMID- 1641688 TI - Beri-beri: age-gender bias in The Gambia. AB - This paper investigates a suspected outbreak of beri-beri which occurred in The Gambia in 1988. The outbreak was spatially specific and had a distinct age and gender bias, with young men aged 15-49 being the group mainly affected. The age and gender bias of the outbreak is particularly interesting as women and children in the developing world are usually more susceptable to conditions associated with malnourishment, than men. The authors investigate the peculiar nature of the outbreak and find that they cannot easily explain the apparent age and gender bias. The authors note that at the time of the outbreak medical treatment took precedence over socio-economic investigations. This makes it difficult to ascertain why certain age and gender groups were affected and thus to target them for future preventative health education programmes. This case study therefore concludes, that where possible, medical investigations must be combined with socio-economic studies if future outbreaks of this kind are to be avoided. PMID- 1641689 TI - The impact of formal, informal, and societal support networks on the psychological well-being of black adolescent mothers. AB - Although several researchers argue that informal support systems provide economic and psychological resources for black families, little empirical research is available to inform policy and intervention programs. This article examines the impact of informal, formal, and societal support systems on the mental health of black adolescent mothers. Using the social work generalist theoretical framework, several types of resources are considered separately to determine whether they contribute similarly to psychological well-being. Data from a survey of black teenage mothers show that both lay and professional supports were important for the young mother's psychological well-being. Support from a male partner, caseworker contact, and membership in a support group decreased psychological distress and depression. Support from the male partner also enhanced psychological well-being. Support from friends, on the other hand, was associated with higher levels of psychological distress. A professional service plan that effectively incorporates informal and societal supports in a complementary manner offers the best possibility for reducing the distress of black teenage mothers. PMID- 1641690 TI - Legal requisites for social workers in child abuse and neglect situations. AB - Societal efforts to protect endangered children have resulted in increased responsibilities for social workers, who are expected to identify, report, and provide testimony in suspected cases of abuse and neglect. Their decisions in these cases may have profound consequences for children, families, and themselves. This article increases social workers' knowledge of legal requisites and system realities in child protection to help them make high-quality decisions. PMID- 1641691 TI - Therapeutic processes in professional and peer counseling of family caregivers of frail elderly people. PMID- 1641692 TI - Drug use and AIDS risks in a soup kitchen population. AB - Untreated substance users remain beyond the reach of most acquired immune deficiency syndrome (AIDS) prevention efforts. In an effort to describe the risk behavior and attitudes of this population, the authors conducted interviews with 148 drug users in an urban soup kitchen. The study focused on subjects' risk taking and risk-reduction behavior related to injection drug use, perceived changes in risk behavior, perceived risk for contracting AIDS, and socioeconomic and attitudinal correlates of injecting and sharing needles. Study findings underscore the need for community-based AIDS prevention strategies to intervene with high-risk populations beyond the reach of drug treatment and AIDS prevention programs. PMID- 1641693 TI - [Comparison of administration of low doses of bromocriptine and levodopa in the early treatment of Parkinson disease]. AB - Results og an open, controlled three-month clinical trial of therapeutical efficacy of a combination of a low doses of levodopa/carbidopa and bromocriptine in 20 de novo patients with Parkinson's disease (PD) are presented. All patients received the same daily doses of levodopa/carbidopa (250 mg), while daily dosage of bromocriptine was gradually increased from 1.25 mg to 30 mg. Owing to development of adverse effects 3 patients dropped out of the study, while in 70% of the patients who completed the protocol improvement of motor functioning exceeded 50%. Those with bradykinesia and rigidity responded most favorably. For all our patients the mean daily dose of bromocriptine was 26.25 mg. The most common adverse effects of the therapy were orthostatic hypotension (7 pts) and nausea (5 pts). The results of the study coincide with the hypothesis that comparative administration of low doses of bromocriptine and levodopa is the best approach to treatment of early phases of PD. PMID- 1641694 TI - [The effect of hyperprolactinemia on biohumoral parameters of bone metabolism in women of reproductive age on chronic hemodialysis]. AB - The study was carried out on a group of 20 women in reproductive age on chronic haemodialysis and on a control group of 11 healthy women. The women on a regular haemodialysis were divided into two subgroups: normoprolactinaemic and hyperprolactinaemic. The following parameters of bone metabolic changes were studied: serum calcium, phosphorus, alkaline phosphatase, pharathormon, osteocalcin, calcitonin, and also LH, FSH, prolactin and estradiol. The values of serum Ca, P, AP, PTH, CTC, OS and of LH and FSH were significantly higher in women on haemodialysis. The hyperprolactinaemic women on haemodialysis had lower values of bone metabolic parameters than normoprolactinaemic women. Hyperprolactinaemia did not significantly contribute to acceleration of bone metabolic changes which were already very accelerated due of secondary hyperparathyroidism. PMID- 1641695 TI - [Intravenous loading doses of sodium phenobarbitone in the treatment of status epilepticus]. AB - Over a period of nine months 14 adult patients with status epilecticus were treated with intravenous loading dose of phenobarbital-sodium. The initial dose was 9 to 12 mg/kg of body weight; it was increased to 36 mg/kg when seizures were stopped. The rate of infusion was 100 mg/min. In 11 of 14 patients (79%) this treatment was effective. The dose ranged from 9 to 14 mg/kg in ten patients and 36 mg/kg in the remaining one. Seizures stopped during the first minute of infusion in nine patients. This treatment was unsuccessful in 3 patients. The rate of infusion was faster in the group where the therapy was successful. In this group higher plasma levels of phenobarbital were obtained with smaller loading doses than in the other patients. Side-effects were mild and transient; they comprised prolonged postical depression of consciousness. No respiratory or cardio-vascular side-effect were observed. There was no potentiation of side effect with subsequent application of intravenous diazepam. We conclude that intravenous phenobarbital-sodium is highly effective and safe in the treatment of status epilecticus. PMID- 1641696 TI - [Antimicrobial sensitivity of Haemophilus influenzae strains isolated from children]. AB - Antibiotic susceptibility of 1308 Haemophilus sp. strains isolated in children was evaluated over a 6-year period. Based on their source and clinical presentation all strains were divided in three groups. The first group consisted of 1264 strains obtained by throat and nasal swab; the second of 30 mucosal strains isolated in children manifesting non-invasive infection and the third of 14 invasive strains, Haemophilus influenzae(Hi)tip b, isolated from blood, CSF, pleural and synovial effusion. The isolates of the first and the second group demonstrated high susceptibility (90%) to chloramphenicol, erythromycin, and ceftriaxone, lower (70-90%) ampicillin and trimethoprim-sulfamethoxazole and low susceptibility (less than 25%) to penicillin, lincomycin and cefalexin. Invasive strains of Hi tip b were resistant to multiple drugs, showing susceptibility exclusively to chloramphenicol, erythromycin and ceftriaxone. Guidance for the treatment of the invasive and non-invasive infections and chemoprophylaxis are discussed. PMID- 1641697 TI - [Osteomyelitis after malleolar fractures]. AB - Over a ten-year period, 485 patients suffering from malleous fracture were operated at the Department for Orthopaedic Surgery and Traumatology in Novi Sad. Postoperative infection appeared in ten cases (2.06%). Eight of these patients primarily had open fractures, and two of them had closed ones. Osteosynthesis of the lateral malleous had most frequently been treated by the use of panel and screws. Staphylococcus aureus was isolated as symptom of the infection in eight cases. In treatment of malleous osteomyelitis, the debridement of focus of infection together with fixation material extraction was the most frequently performed operative method. During a two-year period no exacerbation, seven patients was observed while at control examination three patients had secretion from fistula. Mobility of ankle joint was limited in most cases, while walking imposed no pain. PMID- 1641698 TI - [The effect of penicillamine in copper-processing workers]. AB - Workers working in copper alloy factories (n = 40) who are professionally exposed to smoke and dust of copper, zinc, lead and cadmium and workers who are not exposed to toxic noxae (n = 15) were perorally administrated penicillamine for three days in order to evaluate deposits of these metals in their organisms. On the basis of the results obtained after penicillamine administration it was concluded that this substance can be useful in the evaluation of the presence of copper in workers. Penicillamine mobilisatory effect on lead and zinc in the organism was also proved. Because of competitive relations between copper and zinc (copper was a dominant noxa) it was not possible to evaluate the internal zinc presence. The mobilisatory effect of penicillamine on cadmium in the organism was not observed. PMID- 1641699 TI - [The intrathecal manometric lumbar infusion test (Katzman Test) in the diagnosis of normotensive hydrocephalus]. AB - Over 12-months 17 patients were admitted to the hospital for the presumed diagnosis of normal pressure hydrocephalus (NPH). Four patients had cardinal signs of the syndrome: gait disturbance, dementia and urinary incontinence. Six patients had gait disturbance and dementia. Five patients had gait disturbance and ventricular enlargement on CT scans of the brain, while the last two patients had only urinary incontinence and dementia. All patients underwent neurological examination and CT scans. Clinical and radiological results of these patients were compared with the results of the Katzman's test. Katzman's test was performed in all patients. Physiologic solution of 0.9% NaCl was infused in the lumbal subarachnoid space. The rate of infusion was 1 ml/min during 60 minutes. Cerebrospinal fluid (CSF) pressure was recorded simultaneously using metal aneroid. The test was considered positive if either CSF pressure over 300 mm H2 or undulating waves were recorded at any time of the test. Katzman's test was positive in 12 patients (9 of them with NPH). The undulating waves were recorded in 6 patients (5 with NPH). Four of them experienced tachycardia, hyperventilation, cephalea and mild confusion during the test. The test was positive in all 9 patients with NPH but also in 3 patients with different but pathophysiologically similar disorders. The test was positive in all 4 patients with the characteristic clinical triad of the syndrome and also in all 4 patients with periventricular hypodensity on their CT scans. No patient without gait disturbance had positive test. All except one patient with focal signs or pronounced cortical atrophy, besides with dramatic clinical improvement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641700 TI - [The importance of changes in the septal Q wave induced by exercise in the detection of ischemic heart disease]. AB - Among the numerous variables measured by the electrocardiogram during exercise little attention has been paid to the "septal" Q wave. We examined changes of the "septal" Q wave amplitude during exercise in 43 patients with chest pain. Coronary arteriography showed significant changes in 23 patients and normal arteries in 20. The Q wave amplitude was measured in leads V4-V6 immediately before and at the peak of submaximal bicycle exercise. The amplitude of "septal" Q wave increased during exercise in 11 (55%) patients, and decreased or was not changed in 9 (45%) of the normal subjects (p greater than 0.05). However, the Q wave amplitude increased in 6 (26%) patients, and decreased or was not changed in 17 (74%) patients with ischaemic heart disease (p less than 0.05). Thus, the sensitivity of Q wave analysis in the detection of coronary disease was 74% (p less than 0.05), but specificity was only 55% (p greater than 0.05). PMID- 1641701 TI - [Juvenile ankylosing spondylitis and the joint hypermobility syndrome]. AB - The problem of correlation of rheumatic diseases with mobility of joints in children and young individuals was not frequently been considered. The first of a few authors was C.J. Sutro who was concerned with this problem in 1947. The goal of our treatment was to prevent as long as possible the onset of ankylosis in our patients. They were treated by NSAID as well as by intensive kinesi- and hydrotherapy. All these patients, besides HLA-B27 have also A2 antigen, a possible gen for hypermobility. A prospective study should explain the significance and role of A2 antigen in these patients. PMID- 1641702 TI - [The attitude toward persons with epilepsy]. AB - The attitude of 50 employees and 50 students to epileptic patients was studied with the use of the classical scale of Likert's type. It was found that students were more tolerable then the employees. However, they all were humanistic only when general principles were in question i.e. that epileptic persons should not be avoided, but not also in personal contacts (emotional, close relation, professional). The obtained results confirmed the presumption that the problems related to the difficult employment and family-establishment of epileptic subjects was the consequence of negative attitude and prejudices of the environment to such persons. The secondary handicap due to illness frustrates the normal life of these individuals sometimes more than epileptic attacks. This is one of the reasons why physicians should pay additional attention to this problem during the treatment of epileptic patients. PMID- 1641703 TI - [Epidermoid cyst of the spleen]. AB - A 33-year old woman with 6 x 6 cm splenic cyst of the lower pole of a moderately enlarged spleen, found during ultrasonographic examination for epigastric and left subcostal abdominal pain, is presented. At operation the spleen of 900 grams with a subcapsular cyst in pedunculated extension of the lower splenic pole, ie. accessory lobe, was removed. No other abdominal disease was found. Postoperative recovery was uneventful. Pathohistological examination revealed a cyst, 6 cm in diameter, with whitish wall filled with dark-red turbid fluid containing yellow flocules. The wall of the cyst consisted of the fibrous connective tissue with sclerotic and hyaline changes. The cyst was entirely lined by the stratified squamous epithelium, in some areas flattened, transformed into endothelium. Diagnosis of a very rare splenic epidermoid cyst in the "accessory lobe" of the lower pole, was confirmed. PMID- 1641704 TI - [Disseminated zygomycosis in patients with acute leukemia]. AB - The authors present two patients with acute myeloid leukaemia and pulmonary disseminated form of zygomycosis developed during the period of bone marrow aplasia. Diagnosis was established on necropsy on the basic of the patho histological finding of wide, short and nonseptate hyphe with irregular branching. Hyphe were clearly recognized on Gomori methenamine Silver stained preparations. There were multiple haemorrhagic-necrotic infarcts of different organs due to the mycotic invasion of blood vessels. The authors discuss some some important diagnostic and therapeutic problems. PMID- 1641705 TI - [Perforated ulcer in Meckel's diverticulum]. AB - Three cases, two women and one man, aged 27, 47 and 79 years with perforated peptic ulcer of Meckel's diverticulum are reported. All patients had diffuse peritonitis. The exact diagnosis of the cause of peritonitis has not been preoperatively established in any of them. In two patients cuneiform excision (diverticulectomy) was performed, and resection and anastomosis of the small intestine in the third. The female patients, aged 79, after an uneventful recovery suddenly died due to an acute heart failure on the eight day after surgery. In other patient suppuration of the wound occurred and convalescence was prolonged. In all cases microscopic examination revealed ectopic gastric mucosa on the top of the diverticulum with peptic ulcer. PMID- 1641706 TI - [Intra-arterial administration of prostaglandin E1 in occlusive arterial diseases]. AB - The authors present their result of a two-year follow-up of 106 patients to whom an intra-arterial perfusion of prostaglandin E1 was administered, as limb salvage procedure. The patients were in the IIIrd and IVth stage of occlusive diseases by Fountain, and surgical reconstructions were not possible. All patients were divided into five groups: A--diabetic angiopathy (5), B--distal form of atherosclerosis (40), C--diabetic angiopathy and atherosclerosis (45), D--Burger disease (10) and E--adjuvant therapy in reconstruction with poor run-off (6). The Doppler sonographic and angiographic measurements were performed. After transcutaneous (16 cases), or intraoperative (90 cases) introduction of the catheter into superficial of profunda femoral artery, a continuous intraarterial administration of prostaglandin E1 was carried out in a dose of 10 nanograms/kg body weight/minute (total dosage 3000 nanograms). The patients were controlled immediately after the treatment, as well as 1, 3, 6, 12, 24 and 36 months after the treatment. In efficiency of the treatment was estimated on the following basis: elimination of rest pain, healing of trophic ulceration and demarcation of gangrenous processes. Our late results of intra-arterial administration of prostaglandin E1 proved to be a very successful limb salvage procedure. The treatment was more successful in a connections between the upper knee arterial net and pedal arterial arches were preserved. PMID- 1641707 TI - [Feasibility of use and limitations of the 3D-MR study technique. Results of 5 years' clinical experience]. PMID- 1641708 TI - [Plain and dynamic computed tomography in liver cirrhosis]. PMID- 1641709 TI - [Ochronosis of the lumbar vertebrae]. PMID- 1641710 TI - Cystic fibrosis. Part II. New developments in cystic fibrosis--implications for carrier detection and genetic counselling. AB - Cystic fibrosis (CF) is an autosomal recessive disorder found predominantly in people of European origin. Prenatal diagnosis for this disorder is now possible using the polymerase chain reaction technique to detect the most common CF causing mutation, delta F508. Case studies of prenatal diagnosis and carrier detection are presented and some of the genetic counselling issues related to these investigations are discussed. PMID- 1641711 TI - The frequency of the delta F508 mutation in the cystic fibrosis genes of 71 unrelated South African cystic fibrosis patients. AB - The common delta F508 mutation is present in approximately 70% of mutant cystic fibrosis (CF) genes of European and North American populations. The frequency of the delta F508 mutation has been established for two groups of South African CF subjects. The mutation was found to be present in 82% and 53% of CF genes of white and coloured (i.e. of mixed ancestry) subjects respectively. These findings assist in providing appropriate counselling to individuals who have a family history of CF and in defining laboratory strategies for the establishment of an efficient genetic service for cystic fibrosis. PMID- 1641712 TI - Screening for syphilis and neurosyphilis in acute psychiatric admissions. AB - The value of blood screening for syphilis and cerebrospinal fluid (CSF) screening for neurosyphilis in acute psychiatric admissions is assessed. Of 1,296 patients, 248 (19%) had evidence of previous or current syphilis as shown by a positive Treponema pallidum haemagglutination test, and 68 (5.2%) had potentially treatable syphilis as shown by a positive Venereal Disease Research Laboratory (VDRL) titre. CSF examination was performed on 169 patients with a positive blood test. Seventeen (i.e. 1.3% of all patients included in the study) met our criteria for neurosyphilis. The best predictor for neurosyphilis was the presence of a reactive serum VDRL. However, it is recommended that all patients with a positive blood test and symptoms that could possibly be ascribed to neurosyphilis undergo CSF examination. PMID- 1641713 TI - Frequency of mutant cystic fibrosis genes in South Africa. PMID- 1641715 TI - Speech and hearing problems in a high-risk population. AB - A retrospective study was conducted on 85 neonatal intensive care unit (NICU) survivors, all of whom had been mechanically ventilated. Mean birth weight was 1,726 +/- 778 g and mean gestational age was 32.3 +/- 3.8 weeks. Infants were evaluated for various risk factors previously reported to cause hearing loss. Language development was assessed using the Early Language Milestone (ELM) scale and hearing was tested by free field responses (FFR). Twenty-four children (28.2%) had an abnormal ELM or FFR result. Seventeen children failed an FFR; 14 of these were normal on follow-up and 3 defaulted. There was thus no permanent sensorineural hearing loss in the sample assessed. Eleven children failed an ELM, of whom 5 had speech problems on long-term follow-up. There was a significant correlation between the ELM and neurodevelopmental scores (P = 0.045). Intraventricular haemorrhage also correlated significantly with the ELM score (P = 0.0016). Thus the overall incidence of hearing loss in this NICU population was low, but there was a significant occurrence of speech problems, which correlated with neurological damage. PMID- 1641714 TI - Flunarizine--effective add-on therapy in reading epilepsy. AB - Since it was first described in 1956, reading epilepsy, an uncommon disorder, has engendered great interest among neurologists, the reason being that it is probably one of the most complex of the sensory-evoked reflex epilepsies and one in which the mechanism of seizure production is as yet unresolved. Unfortunately, it often defies the standard medications useful in the treatment of other forms of epilepsy. A patient with typical reading epilepsy, preceded by jaw-jerking, is described in this report. An additional feature of this case is the presence of a stutter from early childhood. Therapy with phenytoin, carbamazepine and sodium valproate failed to provide satisfactory control. Flunarizine, as add-on therapy to sodium valproate, produced an excellent therapeutic response. PMID- 1641716 TI - A safer anaesthetic airway for paediatric adenotonsillectomy. PMID- 1641717 TI - No need for needs norms--why central planning cannot work for health care. AB - It is widely recognised that South Africa, like other countries, has inequities in health and in access to health care. Centralised formal planning is used by the Department of National Health and Population Development and advocated by others as the approach to social justice and equitable distribution of health care resources. This approach is typical of the central planning of command economies. The reasons why central planning cannot work for health care are explained and an alternative approach is suggested which emphasises decentralised management. This is in line with recent policy statements by the Minister of Health that place a high priority on decentralisation and democratisation. The proposal has important implications for the way in which information systems are developed and used. Much information that central planners say they need is also required for effective management, but with some crucial differences. Planners use ad hoc historical information with little understanding of the local context. Managers, in contrast, regularly need current information for use within the local context. It is therefore recommended that efforts by central planners to acquire information be redirected towards building the capabilities of the health care services to provide and use information for management at all levels. PMID- 1641718 TI - Tetracyclines in myalgic encephalomyelitis--fad or fact? PMID- 1641719 TI - Ethical issues in the transformation of health policy in South Africa. AB - There have, of late, been repeated calls for the transformation of the South African health care system. While there are political and economic consequences involved, there are also bio-ethical sequelae. This paper attempts to explore some of the bio-ethical dilemmas that confront both the 'consumers' and the architects of a new health policy (including the State; professional health groupings, e.g. the Medical Association of South Africa; and the so-called progressive health organisations, e.g. the National Medical and Dental Association and the South African Health Workers' Congress). While the literature has focused on libertarian and utilitarian ethical theories, communitarian perspectives are not often mentioned. This paper attempts to redress this perceived deficit. PMID- 1641720 TI - Dying and 'euthanasia'. AB - Medical progress, secularisation of life, growing acceptance of individual human rights (including the right to refuse medical treatment) and of shared decision making in medicine have focused public attention on the ways in which life may, and perhaps even ought to, be allowed to end in our complex modern era. Intense and thoughtful bio-ethical debate over many years has 'unpacked' the many different understandings and interpretations of the word euthanasia. The consequent conceptual clarification together with recognition and acknowledgement of psychological implications has facilitated a growing rational consensus on openly accepting the withholding and withdrawing of treatment (under defined conditions) within the realm of sound medical practice. This is clearly distinct from assisted suicide and active euthanasia which are generally considered unacceptable perversions of medical practice. Given the ability to sustain life for prolonged periods, often in a permanent state of unconsciousness, the unrealistic expectations of some medical personnel and the lay public, the severe constraints on health care facilities in South Africa and the totally inadequate allocation of resources for highly effective medical treatments, it is appropriate to re-open public debate on the limits of 'striving officiously to keep alive' and on the distinction between 'allowing to die' and 'killing'. Concern that 'rational' arguments reflect moral decay rather than moral progress keeps the debate open and focuses attention on some 'slippery slope' consequences. PMID- 1641721 TI - Cystic fibrosis--controversial issues. PMID- 1641722 TI - Myelopathy in a patient dually infected with HIV-1 and HTLV-I. PMID- 1641723 TI - Allergy genes--how far are we? PMID- 1641724 TI - AIDS--no joke. PMID- 1641725 TI - Pseudopneumothorax or pneumothorax simulated by a skin fold. PMID- 1641726 TI - Strange neonatal scalp skin lesions. PMID- 1641727 TI - [Midazolam for preoperative sedation]. PMID- 1641728 TI - Anthropometry and maximum oxygen consumption of rural black schoolboys. PMID- 1641729 TI - The challenge of AIDS to the medical profession. PMID- 1641730 TI - Botshabelo's vaccination survey. PMID- 1641731 TI - Chemotherapy, medical oncology and nomenclature. PMID- 1641732 TI - Cystic fibrosis. Part I. Frequency of the delta F508 mutation in South African families with cystic fibrosis. AB - Cystic fibrosis (CF) is a common autosomal recessive disorder among people of European origin. With the localisation of the gene locus to chromosome 7q31 and the identification of closely linked polymorphic markers in 1985, it became possible to offer prenatal testing to couples at risk of having CF children, provided a live affected individual from that family was available for investigation. The CF gene, named CFTR, was cloned and sequenced in 1989 and the most common CF-causing mutation, delta F508, identified. A search for this mutation has been carried out in 81 South African white CF families of European origin. Using the polymerase chain reaction (PCR) technique the frequency of delta F508 was found to be 0.81. This mutation was not found in the 1 negroid and the 1 Indian CF family investigated. PMID- 1641733 TI - The vascular blood supply of the second metacarpal bone: anatomic basis for a new vascularized bone graft in hand surgery. An anatomical study in cadavers. AB - After traumatic loss of the index finger the second metacarpal bone is often used as a free graft to reconstruct bony defects of the thumb. Since clinical experience has shown numerous advantages of using a blood supplied bone graft, an anatomical study was performed in 104 cadaveric hands to investigate the vascularization supply of this bone. After dye injections into the arterial system the vascular situation of the second metacarpal was studied and a classification was made. Six variations in arterial vascularization were found. The nutrient vessels to the bone originate from the radial artery or from the deep palmar arch and correspond to variable metacarpal arteries. Selective injection studies via the respective pedicles showed sufficient perfusion and complete dye distribution in the bone. Further dissections could demonstrate the feasibility of raising a pedicled bone graft only partially with preservation of the index finger. The second metacarpal as a vascularized graft may be harvested entirely in serious injuries with destruction of the index finger in emergency cases of skeletal thumb reconstruction or partially as an elective procedure. All types have a useful arc of rotation and their pedicles allow transpositions within the radial side of the hand, especially for applications in the thumb and carpus. The clinical application of these procedures could be shown in five cases. The results of this study therefore provide the anatomical basis for transposition or free microvascular transplantation of the second metacarpal as a vascularized bone graft for a variety of indications in hand surgery. PMID- 1641734 TI - Renal arteries: anatomic study for surgical and radiological practice. AB - The renal arterial supply was analyzed in 266 kidneys dissected from 133 fixed adults subjects. The anatomical findings are presented: 1 hilar artery in 53.3% of the cases, 1 hilar artery with 1 superior pole extra-hilar branch in 14.3%, 2 hilar arteries in 7.9%, 3 hilar arteries in 1.9%, superior polar artery in 6.8%, inferior polar artery in 5.3% and other variations in 8.5%. The urological and radiological implications of these findings in kidney transplantation, renovascular hypertension, renal trauma, interventional radiology, conservative surgery and oncologic surgery are discussed. PMID- 1641735 TI - Frequency and size of ossifications in the caudal attachments of the ligamentum flavum of the thoracic spine. Role of rotatory strains in their development. An anatomic study of 121 spines. AB - Ossifications in the caudal attachments of the ligamentum flavum were studied on 121 dried thoracic spines. Most of them were aged. Frequency increased in a caudal direction. At T12, frequency depended on the orientation of the zygapophyseal joints of T11-12 which determined the range of rotation. When they were of thoracic orientation, allowing large range of rotation, ossifications were present in 83% of cases. If orientation was lumbar, allowing poor range of rotation, ossifications became much less frequent:33%. The size of ossifications was also studied. The smaller were in T1 and T2. In T11 and T12, size also depended on the orientation of the zygapophyseal joints of T11-12. If it allowed important range of rotation, ossifications were large sized. In the opposite case, they were small sized. Ossifications of caudal attachments of ligamentum flavum appear to be a normal feature of the aged lower thoracic spine. Their frequency in a given motion segment seems to be influenced by rotational strains. PMID- 1641736 TI - Growth of the cranial bones in human fetuses (2nd and 3rd trimesters). AB - The increase of the weight of some cranial bones was studied in 30 human fetuses (from 17 to 41 weeks of gestation, both sexes together) by multivariate allometry. The study was performed with a covariance matrix of the log transformed bony weights and the Principal Components Analysis (PCA). The first principal component in PCA accounted for 92.12% of the total variance, and all characters were positively correlated with this component. PCA scaled the growth of the bones in the following sequence: a) with negative allometry: vomer, palatine, mandible and maxillae; b) with isometry (p less than 0.05): zygomatic bone; c) with positive allometry: sphenoid, ethmoid, frontal, occipital, temporal and parietal. During the 2nd and 3rd trimesters of gestation the skull exhibited two different growth rates, i.e., the bony group of the facial skeleton presented lower eigenvalues than the bony group of the calvaria, including the base of the skull. These bones of the calvaria certainly are affected by the high increase in volume of the fetal brain during the prenatal life. The knowledge of the cranial growth is a useful information for the anatomy, anthropology, orthodontics, and several medical specialties: radiology, obstetrics, pediatrics, orthopedics and reconstructive surgery. PMID- 1641737 TI - Anatomical study of the accessory axillary vein. AB - The Accessory Axillary Vein (AAV) was studied in 60 axillae of adult cadavers after fixation in 10% formaldehyde solution. The AAV had an incidence of 56.7% originating in 55.9% from the lateral brachial vein, in 32.4% from the common brachial and in 11.8% from the deep brachial vein. After running upward laterally to the axillary artery and the brachial plexus it ended usually (79.4%) in the suprapectoral portion of the AV. The tributaries of the AAV are the circumflex humeral and muscular veins and rarely the thoraco-acromial and the cephalic veins. The AAV can replace the AV in cases of obliteration of the latter. PMID- 1641738 TI - The relationship between the directions of myocardial bridges and of the branches of the coronary arteries in the human heart. AB - The variations of the direction of the myocardial bundles of the bridges over coronary arteries and branches were studied in relation to the direction of the vessels over which they are found. The investigation was performed on 82 hearts of individuals whose death was accidental and unrelated to cardiac disease. The hearts were obtained from cadavers of individuals of either sex and different racial groups, whose age ranged from 7 to 68 years. The angle between the direction of the musculature and of the vessels may explain why in some cases there is no change in the structure of the "pontine portion" of the wall. PMID- 1641739 TI - Morphologic variants of the proximal knee-joint cavity. An anatomical and radiological study. AB - To study the shapes of the suprapatellar bursa and the suprapatellar septum, 210 specimens were examined anatomically and 2056 patients radiologically. It is possible to classify the variants of the suprapatellar septum into four types on the bases of anatomical aspects. The type of suprapatellar septum determines the communication between the suprapatellar bursa and the knee-joint cavity and influences the proximal extension of the knee-joint cavity. A suprapatellar lateral recess shaped like a saccular space was found on the lateral side of the suprapatellar bursa in just under 20% of the knee joints. There was no corresponding suprapatellar recess on the medial side. Pneumoarthrography is an effective tool for demonstrating the variable structures and spaces of the synovial cavity of the knee joint. The radiological findings correlate with the results of the anatomical studies. PMID- 1641740 TI - Contribution of imaging to the understanding of the female pelvic fasciae. AB - According to the ultrasound and MRI findings, supported by planned dissections, the female perineum is organised around the musculofascial system converging towards the fibrous structure of the central perineal tendon (CPT). Behind the CPT the fascial layers form part of a fibrous assembly extending from the ventral surface of the sacrum to the anal complex, prolonging the direction of the sacral concavity downwards and forwards. On the other hand, in front of the CPT the fasciae fuse to form two aponeurotic bands circumscribing the urogenital fossa. The fascial system is reinforced cranially by the structures of the hypogastric sheath and the uterosacral ligaments. The weak point of the urogenital fossa is partly filled by the urethral-clitoridal-vulvar complex. The perineum so formed plays a cardinal role in stabilising the pelvic viscera. Stress is placed on the firmness of the posterior perineum, a key element in pelvic stability. The posterior perineum is often involved in pathological conditions and a good acquaintance with these structures is essential in defining therapeutic indications. PMID- 1641741 TI - Structural analysis of the mandible by quantitative computed tomography. AB - The study presents quantitative computed tomography (QCT) as a noninvasive method for analyzing the inner bone structure. Randomly selected mandibles from the osteological collection of the "Drago Perovic" Institute of Anatomy, School of Medicine, Zagreb were CT-scanned in five bone areas. Analyzing the densitometry curve in two horizontal levels the relation between the compact and spongy bone and the total amount of bone substance in each area were determined. The smallest bone quantity was found in the area of the neck and angle of the mandible, the areas of most frequent bone fractures. The alveolar part of the bone, apart from the area of the angle, was considerably less thick than the base of the mandible. The compact bone was predominant in all CT-scans. PMID- 1641742 TI - Magnetic resonance imaging of the liver by oblique sections. AB - The authors have applied magnetic resonance imaging (MRI) to the anatomic study of the liver by comparing cadaveric sections with those obtained with MRI. This study deals with sections oblique in relation to a sagittal or frontal plane, whose orientation is determined from landmarks visible on transverse sections. Oblique sections were made in 10 cadavers using an original method. First, adjacent transverse sections were made of the frozen trunk and two landmarks were located in these sections: the course of the middle hepatic v. and the direction of the division of the portal venous trunk. The transverse sections were then stacked and the block so reconstituted was refrozen and then cut in adjacent oblique sections oriented either along the plane of the middle hepatic v. (sagittal oblique sections) or along the plane of division of the portal venous trunk (frontal oblique sections). Oblique MRI sections were made in 15 healthy volunteers, mainly based on the same venous landmarks but sometimes on other landmarks visible on the transverse sections. Oblique MRI sections can be made in the plane of any anatomic structure located in the transverse sections in order to define its position. Sections based on identical landmarks differently oriented in different subjects allow for definition of the individual anatomy of the liver investigated. The frontal oblique sections clearly show the course of the trunk of the portal v. and the junctions of the hepatic vv. with the inferior vena cava. The sagittal oblique sections are particularly useful for investigating the thinnest part of the left side of the liver and also the caudate lobe.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641743 TI - Evaluation of the temporal bone by anatomic sections and computed tomography. AB - Serial Computed Tomography (CT) scans of isolated temporal bones have been obtained in transverse planes at 1.5 mm intervals. Then gross anatomic sections of same temporal bones were taken at 3 mm. intervals in planes parallel to the CT scans. These CT and anatomic sections were evaluated comparatively. PMID- 1641744 TI - Supernumerary head of biceps brachii and branching pattern of the musculocutaneus nerve in Japanese. AB - Out of 546 upper limbs (273 cadavers), supernumerary heads of the biceps brachii were found in 75 limbs (13.7%) of 58 cadavers (21.3%). The form, origin, and insertion of the supernumerary heads, and branching pattern of the musculocutaneus nerve were studied. In addition, the dimensions of the heads were measured. In many cases, the supernumerary head arose from the humerus, between the insertion of the coracobrachialis and the upper part of the origin of the brachialis, and/or from the medial intermuscular septum. In a few cases, a supernumerary head arose from the tendon of the pectoralis major or the deltoid, or from the articular capsule, or from the crest of the greater tubercle. The supernumerary heads typically joined the common belly, or the aponeurosis of the biceps brachii. Some heads joined the belly of the long head or that of the short head. In the examination of the branching pattern of the musculocutaneus nerve, communication between the musculocutaneus nerve and the median nerve was found in 43 out of the 75 limbs (57.3%). The communicating branch ran from the musculocutaneus nerve to the median nerve in 24, from the median nerve to the musculocutaneus nerve in 12, in both directions in 5, or in another type of pattern in 2 out of 43 limbs. Sometimes a branch of the musculocutaneus nerve ran around a supernumerary head and then fused with the present trunk. The presence of a supernumerary head seemed to affect the course and branching of the musculocutaneus nerve. PMID- 1641745 TI - The saphenous postero-medial cutaneous island thigh flap and the saphenous supero medial cutaneous island leg flap (25.10.91). PMID- 1641746 TI - The medial septumcutaneous island thigh flap (25.10.91). PMID- 1641747 TI - Clinical anatomy: the new spirit in anatomy. PMID- 1641748 TI - The surgical anatomy of the dorsal carpal branch of the ulnar artery: basis for a neurovascular dorso-ulnar pedicled flap. AB - In order to design a neurovascular flap from the dorso-ulnar aspect of the midhand for pedicled transfer to adjacent or distant locations, the surgical anatomy of the dorsal carpal branch of the ulnar artery (DCBUA) was studied in 12 cadavers. The DCBUA was identified in all specimens. It originates from the ulnar artery 1.6 to 4.4 centimeters proximal to the ulnar styloid, passing deep to the flexor carpi ulnaris tendon, and spirals superficially to the extensor retinaculum around the ulnar border of the wrist. Its terminal branches supply an undetermined area of skin overlying the ulnar metacarpals and the ulnar hypothenar region, either by direct cutaneous supply (3/12 specimens) or by septo cutaneous perforators (8/12 specimens). The DCBUA is closely related to the dorsal sensory branch of the ulnar nerve, with which it supplies a common neurovascular territory. PMID- 1641749 TI - [Etiopathogenetic aspects of medial osteochondrosis dissecans tali]. AB - In a cadaveric biostatic model the pressure distribution at the weightbearing ankle has been investigated under different joint positions and stages of artificial lateral ligament dissection mimicking a supination trauma. The location of the transduced contact area, the size of these areas and amount of pressure were evaluated after application of axial load. The results showed that the location, size of contact area and the maximum transduced pressure were depending on the joint position and stage of ligament dissection. Interestingly the peak pressure was located at the medial talar rim even without lateral ligament dissection. The transduced pressure areas were located at that locations were osteochondral lesions are mostly observed. In regard to these results the etiology and pathogenesis of osteochondritis dissecans tali is discussed. It is thought that supination traumas as well as other biomechanical factors such as overweight and lax ankle ligaments have an important influence on the development of osteochondritis dissecans at least at the medial rim of the talus. PMID- 1641750 TI - [Stress on the upper ankle joint in tennis-specific forms of movement]. AB - The permanently increasing number of injuries in tennis, which are mainly located at the lower extremity, indicates that the internal load e.g. applicated to the ankle during certain movements might be a critical factor. In the present study the relationship between calculated ankle load and muscle forces appearing during tennis techniques performed in a laboratorial setup and some varying parameters such as playing surface, footwear and individual differences in movement structure were investigated. It could be shown that on a felt tennis floor due to its frictional characteristics the midfootstriking subject produced the highest ankle load, while the heelstriking technique reduces the load as well as the change of the playing surface to a floor with loose granulate. In addition it should be considered that external forces (e.g. gained from a force plate) must not be used as predictors for internal load. The presented data show that the model-aided load calculation (MALC) from two trials with similar ground reaction forces leads to completely different values of e.g. the ankle-joint force. PMID- 1641751 TI - [Measuring the cartilage thickness in the patellar gliding articulation with ultrasound--method and value]. AB - An ultrasonographic method for standardized measurement of cartilage thickness in the patellar gilding articulation is presented. A total of 778 kneejoints was investigated. The measurements from 438 healthy kneejoints were analysed with regard to their correlation with sex, age, height and weight, and norm values wer calculated. These were compared with the measurements from 130 kneejoints with "retropatellar pain syndrome". It could be demonstrated that the cartilaginous covering of the patellar facies in "retropatellar pain syndrome" is significantly thinner on the whole (but in particular at the medial facet) than in the healthy kneejoint; after intra-articular chondroprotective treatment, this difference could no longer be demonstrated in 71 kneejoints which were followed up sonographically. The precision and the reliability of the measurement could be verified statistically, so that it is feasible to make a contribution not only to noninvasive diagnosis of retropatellar symptoms, but possible also to better appraisal of the efficiency of therapy measures. PMID- 1641752 TI - [The value of dynamic examination methods in instability of the shoulder joint]. AB - We prospectively examined 25 patients with shoulder instability by clinical examination and by fluoroscopic and sonographic imaging. 14 patients were classified as recurrent, posttraumatic instabilities, 12 of these anterior and two posterior. Clinical examination revealed the direction of instability in 5 patients, fluoroscopy in 5 and sonography in 3 patients. 11 patients had non traumatic recurrent instabilities. Of these, clinical examination and fluoroscopy demonstrated identical directions of laxity in 8. Sonography concurred with the other techniques in only three cases. We recommend manual instability testing followed by fluoroscopy for evaluation and documentation of patients with non traumatic, recurrent shoulder instability. Posttraumatic instabilities should be diagnosed with other, static procedures. PMID- 1641753 TI - [Supinator tunnel syndrome--a differential diagnosis of so-called tennis elbow]. AB - The increasing activity in sport lead especially in untrained persons to overstress of the elbow joint. Often one tends to diagnose a epicondlylits humeri radialis i.E. tennis elbow. In 1873, Runge (16) first described what we now call epicondylitis humeri radialis, i.e. what Morris (10) 1882 called "Tennis elbow." Its etiology is still under discussion, and the diagnosis of tennis elbow necessitates exact and detailed differential diagnostic efforts. In the work presented, we describe one major differential diagnosis, the posterior interosseous nerve syndrome or supinator entrapment syndrome. With sketches and anatomical preparations we describe the course of the radial nerve around the elbow joint and of its ramus profundus within the supinator muscle pouch. Listing representative causes of this syndrome, we also comment on clinical aspects and our surgical method of choice. We have interviewed and reexamined 6 of our patients suffering from a so called therapy-resistant epicondylitis humeri radialis. Due to their clinical picture all six had been operated for posterior interosseous nerve syndrome/supinator muscle entrapment syndrome. We present our results including neurophysiological evaluations. In relapsing, therapy resistant and diagnostically untypical humeral radial epicondylitis, a posterior interosseous nerve syndrome should be considered. After clinical and electromyographic examination a revision of the supinator channel is justified in selected cases. PMID- 1641754 TI - [Diagnosis and therapy of tendinitis exemplified by the athletic horse]. AB - This paper reviews the literature and describes our experiences in the diagnosis and treatment of tendinitis in horses. Ultrasonography provides a sensitive tool to diagnose tendinitis and quantitate the degree of damage to the tendon; as well as provide differential diagnoses such as peritendinitis. The principles in therapy of acute tendinitis are: Immediate reduced exercise or rest, physical therapy to reduce inflammation and administration of local and systemic antiinflammatory drugs. The goal is restoration of the tensile strength of the tendon without peritendinous granulation tissue and adhesions. To achieve this goal it is important to maximize the intrinsic healing and to minimize the extrinsic healing. Any form of counterirritation is forbidden because of increase of inflammation. Passive motion and massage will help to increase blood flow and to decrease adhesions. Local injection (peritendinous and intratendinous) of hyaluronic acid seems to increase the intrinsic healing and to decrease adhesions without side effects. Depending on the extent of the tendon damage, which tendon is involved and the progress toward healing controlled ultrasonographically, the healing period can be divided in 4 phases: 1. Immobilisation (Cast), only in severe cases (for 1-2 weeks). 2. Passive motion and massage (starting as soon as possible, usually at once during bandage change). 3. Careful exercise, hand walk or walk under saddle (for 1-6 months, starting as soon as possible, usually about 5 days after initial treatment). 4. Controlled slow and gradual training, no turnout, long or pasture (for 1-6 months, after phase 3). Chronic tendinitis is often caused when the severity of the initial injury is underestimated and the treatment inappropriate. Chronic tendinitis is treated using similar principles starting with phase 2. Tendon splitting and other surgical approaches have been used in selected cases to enhance the prognosis. PMID- 1641755 TI - To be or not to be? PMID- 1641756 TI - Spin trap salvage from endotoxemia: the role of cytokine down-regulation. AB - BACKGROUND: The spin trap alpha-phenyl-N-tert-butyl-nitrone (PBN) affords protection from the lethality of septic (lipopolysaccharide) shock. We hypothesized that PBN may work through down-regulation of the sepsis-induced cytokine cascade. METHODS: C3H/HEN mice received 30 mg/kg lipopolysaccharide 15 minutes after pretreatment with PBN or vehicle. Animals were monitored for differences in behavior, histopathologic studies, survival, and serum levels of tumor necrosis factor (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin 6 (IL-6) after lipopolysaccharide. Northern blot analyses of TNF, IFN-gamma, c fos, and IL-6 transcripts were also performed. RESULTS: Seventy-two-hour survival was significantly higher in the PBN-treated (59/60) compared with the saline treated animals (13/60; p2 less than 0.005), and the PBN group exhibited a blunted endotoxemic response. TNF levels were significantly lower in the PBN treated animals at 1 to 6 hours, whereas IFN-gamma levels were depressed at 8 hours. PBN down-regulated TNF transcription at 30 minutes, with maximum lowering of all cytokine transcripts at 6 hours. PBN depressed c-fos transcription within 15 minutes of lipopolysaccharide injection. CONCLUSIONS: Spin trap protection from endotoxemia may be related to interruption of the cytokine network, with profound effects on transcription and protein elaboration. Such compounds may prove useful in not only sepsis but also other cytokine-free radical-related pathophysiologic alterations. PMID- 1641757 TI - Glutathione deficiency increases organ dysfunction after hemorrhagic shock. AB - BACKGROUND: Reactive oxygen metabolites contribute to tissue destruction in a wide variety of diseases. Glutathione, a potent endogenous antioxidant, neutralizes the destructive potential of free radicals, but this tripeptide may be depleted during illness. We hypothesized that glutathione deficiency would amplify organ dysfunction after shock in rats. METHODS: Rats received either diethyl maleate to deplete tissue glutathione or a control solution intraperitoneally. The animals were subsequently bled to and maintained at a mean arterial pressure of 40 mm Hg for 30 minutes and then fully resuscitated. Sham animals underwent blood pressure monitoring only. Tissue glutathione, liver and renal function tests, organ bacterial content, and mortality rates were determined 4 and 24 hours after shock. RESULTS: Normal rats subjected to shock and sham animals had similar laboratory chemistry results, organ culture results, and mortality rates. However, glutathione-depleted animals subjected to shock had elevated liver and renal function tests, increased organ bacteria, and a dramatic increase in mortality rates compared with control shock and sham animals. CONCLUSIONS: We conclude that glutathione deficiency predisposes animals to organ failure and death after an otherwise nonlethal period of hypotension. Because glutathione deficiency is associated with severe injury and sepsis, treatment strategies that maintain glutathione stores may decrease the incidence of multisystem organ failure. PMID- 1641758 TI - Energetics of defective macrophage antigen presentation after hemorrhage as determined by ultraresolution 31P nuclear magnetic resonance spectrometry: restoration with adenosine triphosphate-MgCl2. AB - BACKGROUND: The purpose of this study was to determine whether a decrease in macrophage energetics contributes to the profound immune dysfunction that occurs after hemorrhage and, if so, whether adenosine triphosphate (ATP)-MgCl2 treatment has any beneficial effects on the above parameters. METHODS: C3H/HeN mice were bled to a mean blood pressure of 35 mm Hg, maintained at that pressure for 60 minutes, resuscitated with their own shed blood and Ringer's lactate, and treated with ATP-MgCl2 (80 mumol/kg body weight) or saline solution (vehicle). Peritoneal macrophages were harvested 1 hour after resuscitation and ATP levels were determined by 31P nuclear magnetic resonance spectrometry. In addition, macrophage functions were determined by measuring antigen presentation capacity (AP), as well as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) synthesis. RESULTS: Hemorrhage caused a significant decrease in peritoneal macrophage AP function, as well as IL-1, IL-6, and TNF synthesis, by 52% +/- 14%, 91% +/- 12%, 78% +/- 8%, and 89% +/- 8%, respectively, which was correlated with a 78% +/- 6% decrease in macrophage ATP levels (p less than 0.05). Treatment with ATP-MgCl2 after hemorrhage restored macrophage ATP levels (p less than 0.05) and significantly increased (p less than 0.05) macrophage AP, IL-1, IL-6, and TNF release by 110% +/- 21%, 130% +/- 38%, 124% +/- 17%, and 66% +/- 24%, respectively. CONCLUSIONS: The decreased macrophage ATP levels may be the cause of defective macrophage AP and cytokine release after hemorrhage, and both macrophage ATP levels and macrophage immune functions can be restored with adjuvant ATP-MgCl2 treatment after hemorrhage. PMID- 1641759 TI - The role of magnesium in postischemic cardiac dysfunction. AB - BACKGROUND: The biochemical basis for postischemic myocardial stunning is not fully elucidated. Magnesium is an important regulator of cellular energetic processes and excitation-contraction coupling. We hypothesized that the decrease in function in the postischemic period may be the result of an alteration in magnesium regulation. METHODS: In a Langendorf perfused rabbit heart model, we used 31P nuclear magnetic resonance spectroscopy to noninvasively determine intracellular Mg2+ and high-energy phosphate levels in the preischemic period and after a 30-minute period of normothermic ischemia. We measured adenosine triphosphate (ATP), phosphocreatine, and the phosphocreatine/inorganic phosphate ratio and calculated the free energy of ATP hydrolysis (delta GATP). On reperfusion, hearts were divided into three groups (n = 7 per group)--those receiving unmodified Krebs-Henseleit (control), 192 ng/ml dobutamine, or 5 mmol/L pyruvate. RESULTS: Function (expressed as the rate-pressure product) was approximately 77% of preischemic values in the control group, whereas in both dobutamine and pyruvate groups it returned to preischemic levels. ATP was decreased similarly in all groups in the postischemic period. Phosphocreatine/inorganic phosphate ratio and delta GATP were higher in the pyruvate group compared with the other groups. Intracellular Mg2+ was elevated significantly in the unmodified control postischemic group compared with preischemic, postischemic dobutamine, and pyruvate groups (1.0 +/- 0.12 vs 0.80 +/- 0.08, 0.64 +/- 0.08, and 0.70 +/- 0.05 mmol/L, respectively; p less than 0.05). CONCLUSIONS: We conclude that (1) postischemic "stunned" hearts have elevated Mg2+ levels in association with impaired contractile function, (2) inotropic agents improve contractile function in association with a decline in Mg2+ to preischemic levels despite differing effects on intracellular energetics, and (3) Mg2+ may play an important regulatory role in the heart after ischemia. PMID- 1641760 TI - Growth hormone attenuates the abnormal distribution of body water in critically ill surgical patients. AB - BACKGROUND: Catabolic illness is associated with fluid retention and extracellular space expansion. To determine the effect of human growth hormone (GH) on body water compartments, critically ill surgical patients were studied for a 2-week period during which they either continued to receive standard intensive care unit support, or in addition, received GH, 10 mg/day. METHODS: Body water compartments were measured at the beginning and end of the period by the indicator dilution technique with sodium bromide and heavy water used as the indicators of extracellular (ECW) and total body water (TBW), respectively; intracellular water (ICW) was calculated by subtraction. RESULTS: Neither group lost significant amounts of weight or TBW. A marked ECW expansion and disturbance of the ECW/TBW ratio occurred in the patients receiving standard care, which was associated with a dramatic reduction in ICW, a critical component of the body cell mass (BCM). In contrast, GH-treated patients maintained ECW and ICW, indicating a preservation of BCM, and their ECW/TBW ratio normalized. CONCLUSIONS: GH administration prevents ECW retention and stabilizes or normalizes fluid distribution during critical illness. Taken together with its known anabolic effects under these conditions, the maintenance of ICW demonstrates that GH can be used to preserve BCM in complex surgical patients. PMID- 1641761 TI - The influence of ethanol on pancreatic blood flow in cats with chronic pancreatitis. AB - BACKGROUND: The mechanism by which ethanol predisposes to acute pancreatitis, especially in established chronic pancreatitis, is not known. Here we studied the effects of acute ethanol ingestion on pancreatic blood flow in chronic pancreatitis, a setting characterized by diminished basal blood flow to the pancreas. METHODS: Obstructive pancreatitis was created by partial duct ligation for 3 weeks in nine cats. Controls (n = 8) were not operated on. Blood flow was measured in anesthetized animals with a hydrogen gas clearance technique and an intraductal electrode. Pancreatic interstitial pressure, systemic and portal blood pressures, and serum ethanol levels were recorded, and pancreatic vascular resistance was calculated. Measurements were made before and for 2 hours after 20 cc of 40% (wt/vol) ethanol was instilled into the stomach. RESULTS: Basal flow was reduced in the obstructed pancreas to 51% of normal. Both groups showed an acute decrease in blood flow when ethanol was given. A more steep (50% of baseline) and a more prolonged (120 minutes) fall was observed in the pancreatitis group than in controls (31% and 60 minutes, respectively). The decline in blood flow correlated with increases in interstitial pressure and vascular resistance. CONCLUSIONS: Acute ethanol ingestion sharply reduces pancreatic blood flow, especially in glands with chronic pancreatitis. PMID- 1641762 TI - Neuropeptide release from the isolated, perfused, lower esophageal sphincter region of the rabbit and the effect of vasoactive intestinal peptide on the sphincter. AB - BACKGROUND: The aim was to evaluate the isolated, vascularly perfused, lower esophageal sphincter (LES) as a model for investigating the functional role of neuropeptides such as vasoactive intestinal peptide (VIP). METHODS: At laparotomy the LES was removed along with the distal esophagus, stomach, and left gastric artery and vein. The LES area, isolated from the body of the stomach by a custom made clamp, was perfused with oxygenated Krebs-Ringer bicarbonate solution (pH 7.4, 38 degrees C) via the left gastric artery. The LES pressure was monitored continuously with a custom-made Dent sleeve catheter. LES pressure and release of neuropeptides were investigated after carbachol and VIP were administered alone or in combination. VIP, calcitonin gene-related peptide (CGRP), and somatostatin were measured in the venous perfusate collected from the left gastric vein. RESULTS: LES tone and contraction frequency were similarly increased by 10 and 100 nmol/L carbachol (increment, 4.0 +/- 0.26 mm Hg with 10 nmol/L carbachol; p less than 0.0003). Perfusion with 10 nmol/L VIP decreased basal tone and completely abolished the contraction induced by 100 nmol/L carbachol. VIP, CGRP, and somatostatin were released from the LES in response to 10 nmol/L carbachol (VIP rose from 55 +/- 13 to 179 +/- 24 pmol/L, CGRP, from 114 +/- 30 to 239 +/- 33 pmol/L, and somatostatin from 15 +/- 2 to 27 +/- 4 pmol/L; all p less than 0.001). CONCLUSIONS: These findings support a role for VIP in the inhibitory reflex of the LES but suggest that other neuropeptides may also be involved. The isolated, perfused LES provides a new tool for investigating neuropeptide interactions. PMID- 1641763 TI - Quantitative increases in surgical house officer clinical activity as the basis for increased work loads in a university hospital. AB - BACKGROUND: House officer (HO) work loads, particularly work hours, have been the subject of considerable controversy. The hypothesis of this study was that a disproportionate work burden has been placed on HOs in teaching hospitals because of increased obligatory clinical activities and increased educational expectations. METHODS: Factors directly and indirectly affecting care of surgical patients were related to individual HO efforts at the University of Michigan from 1981 to 1991. Data regarding clinical activity and support services were abstracted for analysis from hospital year-end reports, personnel rosters, and educational logs and correlated with the number of surgical HOs. RESULTS: The total numbers of HOs in the Department of Surgery were relatively constant (122 +/- 4) throughout the study interval. Increases that occurred in annual hospital admissions (7615 to 10,651), discharges (7909 to 11,176), clinic visits (53,251 to 86,111), total operations (6789 to 16,526), and operating room hours (24,175 to 62,429) were significant (r greater than 0.9; p less than 0.001 in each category). The acuity of inpatient hospital care increased twofold, as measured by a case mix index, and was accompanied by a 125% increase in the number of surgical intensive care unit beds. During the study period, department of surgery faculty increased 49% (59 to 88), clinical nursing staff increased 118% (821 to 1794), hospital administrative staff increased 59% (2086 to 3320), and hospital support staff increased 53% (4134 to 6342). The number of students in each University of Michigan Medical School class, a group that might defray certain HO work loads, decreased significantly by 16% (226 to 189) during this time (r = 0.76; p less than 0.02). CONCLUSIONS: Disproportionate increases in work demands have been placed on surgical HOs compared with other health care team members during the past decade. Calculated work loads increased from 91.2 hr/wk/HO in 1981 to 110.9 hr/wk/HO in 1991. Balancing the increasing service activities with educational needs of surgical HOs remains a substantial challenge to be addressed by educators. PMID- 1641764 TI - Enhanced endothelialization of expanded polytetrafluoroethylene grafts by fibroblast growth factor type 1 pretreatment. AB - BACKGROUND: Biomaterial pretreatment with endothelial cell mitogens may enhance endothelialization. METHODS: Modified fibrin glue (FG) containing 1 ng/cm2 recombinant 125I-labeled fibroblast growth factor type 1 (125I-FGF-1), 20 micrograms/cm2 heparin, 2.86 mg/cm2 fibrinogen, and 2.86 x 10(-2) units/cm2 thrombin was pressure perfused into expanded polytetrafluoroethylene (ePTFE) grafts. Grafts were interposed into infrarenal aortas of 24 New Zealand white rabbits and explanted after 0, 5, 30, and 60 minutes and 1, 7, 14, and 30 days. Residual radioactivity was determined by gamma-counting. Remaining 125I-FGF-1 is expressed as percent of value at time 0. To determine the effect of the FG/FGF-1 on graft healing, three groups of 50 x 4 mm 60 microns internodal-distance nonreinforced ePTFE grafts were implanted in the aortoiliac position of 12 dogs. Group I (n = 12) contained the complete modified FG, group II (n = 6) contained FG with heparin but no FGF-1, and group III (n = 6) contained untreated identical ePTFE. Tritiated thymidine (0.5 microCi/kg) was injected intramuscularly 10 hours before explantation after 7 and 28 days for light and electron microscopy and en face autoradiography. RESULTS: Retention of 125I-FGF-1 showed rapid initial loss (delta %/delta min = -24.1) followed by slow loss after 1 hour (delta %/delta min = -0.03), with 13.4% +/- 6.9% remaining at 1 week and 3.8% +/- 1.1% at 30 days. Every FG/FGF-1 graft at 28 days showed extensive capillary ingrowth and confluent endothelialized luminal surfaces, not seen in any specimen of the other two groups. Autoradiography revealed a significant increase (p less than 0.05) in 3H thymidine incorporation in the FG/FGF-1 grafts at 28 days versus all groups as a function of time and graft treatment. CONCLUSIONS: Pressure perfusion of an FGF 1/FG suspension into 60 microns internodal-distance ePTFE grafts promotes endothelialization through capillary ingrowth and increased endothelial cell proliferation. PMID- 1641765 TI - Collagen and elastin gene expression in aortic aneurysms. AB - BACKGROUND: The decreased elastin concentration found in abdominal aortic aneurysms (AAAs) may result from a differential synthetic response wherein elastin gene expression fails to increase in parallel with type I procollagen (COL I) gene expression. The purpose of this study is to determine tissue mRNA levels for elastin and COL I in AAAs compared with levels in normal, age-matched aorta and to determine the relationship between aging and COL I gene expression. METHODS: Total RNA exacted from normal infrarenal aortic tissue (n = 7) and AAA (n = 10) tissue was subjected to Northern analysis. Mean values for COL I, elastin, and alpha-tubulin mRNA levels were compared by use of the Student t test. Age and COL I mRNA levels were analyzed by regression analysis. RESULTS: COL I mRNA was increased significantly in AAAs (1.18 +/- 0.13) compared with normal aortas (0.14 +/- 0.05). A commensurate increase in elastin mRNA (AAAs, 0.11 +/- 0.02, vs normal aortas, 0.39 +/- 0.2) was absent. There was no correlation between age and COL gene expression. CONCLUSIONS: The decreased elastin concentration relative to collagen in AAAs may be explained, in part, by the changes in message level of elastin and collagen. The enhanced COL I gene expression in AAAs is unrelated to age. PMID- 1641766 TI - Glucocorticoids regulate intestinal glutaminase expression. AB - BACKGROUND: The metabolism of glutamine by the small intestinal mucosal cells is highly dependent on the glutaminase enzyme. Because mucosal glutamine utilization is increased after operation, we hypothesized that the elevated glucocorticoid hormones that occur after surgical stress regulate expression of mucosal glutaminase at the molecular level. METHODS: Adult rats received saline solution or dexamethasone (0.5 mg/kg, one dose) and were sacrificed at various times after treatment. Jejunal mucosal total RNA was extracted for Northern hybridization with an alpha-32P-labeled rat glutaminase cDNA. The mRNA of the constitutively expressed gene beta-actin was the control for RNA loading. Quantitation of glutaminase transcripts was determined by densitometric scanning and normalized to actin. Glutaminase activity (micromoles per milligram of protein per hour) and its kinetic parameters, maximal transport velocity (micromoles per milligram of protein per hour) and Michaelis-Menten constant (micromoles per liter), were also determined. RESULTS: Dexamethasone increased glutaminase mRNA (twofold at 4 hours, sixfold at 12 hours; p less than 0.01) and glutaminase-specific activity. The increase in message preceded the increase in activity by 4 hours, consistent with de novo RNA synthesis followed by protein synthesis. The increase in glutaminase activity was the result of a 21% increase in the maximal enzyme capacity (maximal transport velocity = 8.6 +/- 0.5 mumol/mg protein/hr in control rats vs 10.4 +/- 0.3 mumol/mg protein/hr in rats treated with dexamethasone; p less than 0.01) rather than a change in enzyme affinity (Michaelis-Menten constant). CONCLUSION: Glucocorticoids may accelerate intestinal glutamine utilization by increasing glutaminase expression, an adaptive response that could provide more energy for mucosal cells in stress states. PMID- 1641767 TI - Growth hormone and insulin combine to improve whole-body and skeletal muscle protein kinetics. AB - BACKGROUND: A cooperative effect of exogenous insulin and recombinant human growth hormone (r-hGH) with respect to whole-body and skeletal muscle protein metabolism has not been demonstrated previously. This study examined the effect of r-hGH and insulin administration during euglycemic clamping and concurrent amino acid supplementation. METHODS: Twenty-three normal volunteers in the postabsorptive state were either treated with r-hGH for 3 consecutive days before a metabolic study (GH group; n = 10) or not treated (CTRL group; n = 13). The r hGH dose was 0.2 mg/kg/day (n = 5) or 0.1 mg/kg/day (n = 5). All subjects then received an infusion of 14C-labeled leucine and tritiated phenylalanine, followed by measurement of baseline protein kinetics (GH and CTRL). Subsequently a euglycemic insulin infusion (1 mU/kg/min) with concurrent amino acid infusion was administered, and protein kinetic measurements were repeated at steady state. RESULTS: GH and insulin separately produced an increase in whole-body and skeletal muscle protein net balance. GH plus insulin was associated with a higher net balance of protein than was insulin alone. CONCLUSIONS: r-hGH and insulin in the presence of amino acids and glucose combine to improve whole-body and skeletal muscle protein kinetics. PMID- 1641768 TI - Effect of age on wound healing in healthy human beings. AB - BACKGROUND: Although the elderly clinically have a higher rate of wound complications, the physiologic effect of age on wound healing in human beings is unknown. METHODS: Healthy young (18 to 55 years of age) and elderly (more than 65 years of age) human volunteers had a 2 x 2 cm, superficial, split-thickness wound created on the anterior aspect of the thigh, and the rate of epithelialization was assessed. For studies of fibroplasia, similar groups underwent subcutaneous implantation of polytetrafluoroethylene catheters, which were removed after 14 days. Biochemical analyses of the catheters included determinations of hydroxyproline, total alpha-amino nitrogen, and DNA. RESULTS: The elderly volunteers had a significant delay of 1.9 days in epithelialization. Analyses of the subcutaneously implanted catheters showed no difference in DNA content or hydroxyproline-accumulation; however, the young volunteers had a significantly higher amount of total alpha-amino nitrogen. CONCLUSIONS: In healthy humans, aging leads to delayed epithelialization. No effect of age on collagen synthesis was noted, although accumulation of wound noncollagenous protein was decreased. This decrease may impair the mechanical properties of scarring in aged human beings. PMID- 1641769 TI - Beneficial effect of syngeneic pancreatic islet transplantation on liver atrophy and hepatocellular function after portacaval shunt. AB - BACKGROUND: Hepatic insufficiency, which continues to be a source of morbidity after portacaval shunt (PCS), can be prevented by syngeneic pancreatic islet transplantation into the portal vein before PCS. This study investigated the ability of syngeneic pancreatic islet transplantation after PCS to prevent hepatic atrophy and rescue hepatocellular function. METHODS: Approximately 1200 to 1400 syngeneic rat pancreatic islets were transplanted through a heparinized catheter into the left lobes of the liver 3, 7, and 21 days after end-to-side PCS. Normal rats received no treatment, and PCS control rats received PCS only, without islet transplantation. Hepatocellular function (caffeine clearance) and hepatic blood flow (indocyanine green clearance) were analyzed at 42 and 49 days after PCS. On day 51 after PCS, the left and right lobes of the liver were divided, weighed, and sectioned for histologic studies. RESULTS: Caffeine clearance in the animals at 3 days (p less than 0.05) and at 7 days (p less than 0.05) after end-to-side PCS was significantly improved versus control PCS animals, indicating that hepatocellular function could be rescued after creation of a PCS. Indocyanine green clearance of all groups with PCS was significantly (p less than 0.001) decreased versus normal animals, showing that hepatic blood flow was uniformly decreased by PCS in all groups. The weight of the transplanted left lobes was significantly greater than the untransplanted right lobes of the groups at 3 days (p less than 0.01) and at 7 days (p less than 0.05) after end-to-side PCS compared with control animals, indicating that liver atrophy was prevented in the islet-transplanted lobes but not in those lobes without a transplant. CONCLUSIONS: Islet transplantation early after PCS can prevent liver atrophy and significantly improve hepatocellular function. PMID- 1641770 TI - Evaluation of intrathymic islet transplantation in the prediabetic period. AB - BACKGROUND: Beta-cell destruction in type I diabetes mellitus results from a chronic autoimmune process. Exposure of thymic T cells to islet antigens during the prehyperglycemic phase of diabetes may alter the likelihood of autoimmune damage to beta cells in the native pancreas. Thus we evaluated whether prophylactic major histocompatibility complex (MHC)-incompatible intrathymic islet allografts could prevent hyperglycemia and native pancreatic beta-cell destruction. METHODS: At 4 to 6 weeks of age, diabetes-prone BioBreeding rats received intrathymic injection of 1500 to 2000 noncultured MHC-incompatible Lewis islets. No immunosuppression was administered. Age-matched littermates underwent intrathymic injection of saline solution. RESULTS: None of 13 BioBreeding rat recipients of prophylactic intrathymic Lewis islet allografts became hyperglycemic versus 13 of 13 control rats (p less than 0.001). The age at onset of diabetes in the control group ranged from 77 to 104 days (mean, 86 days). Normoglycemia in recipients of intrathymic islet allografts persisted for greater than 8 months after transplantation, and thymectomy (graft removal) did not precipitate hyperglycemia. CONCLUSIONS: Prophylactic intrathymic MHC-incompatible islet allografts effectively prevent hyperglycemia and native beta-cell destruction in an animal model of autoimmune diabetes. Rejection and autoimmune destruction of intrathymic MHC-incompatible islet allografts were not seen after transplantation in the prediabetic (prehyperglycemic) period. Intrathymic islet allografts at an early age (before puberty) preserve native beta-cell function and may prevent or retard thymic atrophy. PMID- 1641772 TI - Retroviral-mediated gene transfer in human hepatocytes. AB - BACKGROUND: The ability to modify human hepatocytes genetically is an essential first step in the development of liver-directed ex vivo gene therapy for inherited metabolic disease. The purpose of these studies was to prove that the genome of human hepatocytes can be altered successfully to express foreign genetic material. METHODS: Human hepatocytes were plated at 2 or 4 x 10(6) cells/10 cm Primaria (Falcon, Oxnard, Calif.) plates. Fresh virus from the amphotropic viral producer cell line BAG, containing the Escherichia coli beta galactosidase gene lacZ, was placed directly onto hepatocyte cultures and quantitative analysis of cells staining positive for the lacZ gene was undertaken. In a different human liver, a variety of viruses from producer cell lines containing clones of the human low-density lipoprotein (LDL) receptor were plated directly on cultures of human hepatocytes, and gene transfer was demonstrated by increased uptake of fluorescent-labeled LDL. RESULTS: Beta galactosidase production in hepatocytes was assayed histochemically with the chromogenic substrate X-gal. The highest percentage of cells staining positive for expression of enzyme was seen at 4 x 10(6) cells/plate (43.66% +/- 1.02% vs 27.99% +/- 2.31%). Gene transfer was also documented by the uptake of fluorescent labeled LDL with a variety of different vectors containing the human LDL receptor. CONCLUSIONS: (1) Human hepatocytes can be cultured in vitro and are susceptible to retroviral infection, (2) functional gene transfer is demonstrated by intracellular function of foreign genes, and (3) the level of expression appears dependent on plating density. We conclude that human hepatocytes are suitable targets for genetic manipulation and may play an important role in human gene therapy trials. PMID- 1641771 TI - Islet xenografts in fully xenogeneic (rat----mouse) chimeras: evidence for normal regulation of function in a xenogeneic mouse environment. AB - BACKGROUND: Transplantation of untreated rat bone marrow into mouse recipients conditioned by total-body irradiation results in fully xenogeneic chimerism (rat- --mouse). The chimerism is stable for up to 10 months, survival is excellent, and there is no evidence for graft-versus-host disease. We recently reported the long term survival (greater than 180 days) of donor-specific pancreatic islet xenografts in these fully xenogeneic chimeras. METHODS: Chimeras were prepared and typed for chimerism at 6 weeks, and diabetes was induced by streptozocin injection. Donor-specific pancreatic islets were placed under the renal capsule and recipient blood glucose levels were followed biweekly. The aim of this study was to examine whether the transplanted pancreatic islets exhibited normal function in a xenogeneic environment and assess whether the islet xenografts were not only sufficient to support euglycemia but also regulated in function in response to a glucose challenge. RESULTS: We report for the first time that donor specific rat islet xenografts were capable of producing normal basal and peak levels of insulin and responding to a glucose challenge in a manner similar to that of normal mouse islets. CONCLUSIONS: These data indicate that donor-specific rat islet xenografts are functional and regulated normally in fully xenogeneic (rat----mouse) chimeras. PMID- 1641773 TI - Epidermal growth factor protects portal hypertensive gastric mucosa in ischemia/reperfusion: the role of capillary endothelia and prostaglandins. AB - BACKGROUND: Epidermal growth factor (EGF) protects gastric mucosa against a variety of injurious agents, but the mechanism is unclear. Because the abnormal microvasculature of portal hypertensive (PHT) gastric mucosa is a major target of ischemia/reperfusion (I/R) injury, we used this model to assess EGF's protective role at the microvascular level. METHODS: Rats with PHT (staged portal vein ligation) received either EGF, 20 micrograms/kg, or saline solution intravenously, with or without indomethacin pretreatment (20 mg/kg subcutaneously). I/R was produced by withdrawing blood to systemic pressures of 30 mm Hg for 20 minutes and reinfusing it. Stomachs were excised 20 minutes later and evaluated for gross and histologic necrosis, microvascular permeability, mucosal ultrastructure and vimentin, and cyclooxygenase immunofluorescence. RESULTS: In saline-treated rats, gross and histologic damage involved 46% +/- 3% of glandular mucosa and 23% +/- 3% of mucosal sections, respectively. Microvascular permeability was increased 43-fold over that of normal control rats. Vimentin immunofluorescence intensity was reduced to 36% +/- 4% that of normal control rats. EGF pretreatment reduced histologic necrosis to 2% +/- 1% (p less than 0.01). Microvascular permeability and vimentin intensity were almost normalized. Indomethacin partially reversed the mucosal protection induced by EGF. CONCLUSIONS: EGF significantly reduces I/R injury to PHT gastric mucosa. Microvascular endothelia of PHT gastric mucosa are the major target of I/R injury and the site of EGF's protective action. Prostaglandins in part mediate EGF's protective action. PMID- 1641774 TI - Oxygen free radical regulation of rat splanchnic blood flow. AB - BACKGROUND: The role of oxygen-derived free radicals on splanchnic prostaglandin (PGI2) synthesis and superior mesenteric artery (SMA) blood flow was examined during acute hemorrhage. METHODS: Sprague-Dawley rats were hemorrhaged to 30 mm Hg for 5, 30, or 45 minutes without (SK5, SK30, and SK45) or with (SK5 + R, SK30 + R, and SK45 + R) blood reperfusion. The SK30 + R and SK45 + R groups were treated with or without superoxide dismutase (10,000 units/kg intravenously). In vivo SMA blood flow was measured continuously for 100 minutes by a transonic flow probe, or in other groups the in vitro-perfused SMA and its end-organ intestine (SV+SI) were assayed for release of PGI2 by radioimmunoassay after 15 and 30 minutes of perfusion. RESULTS: Acute hemorrhage at all time periods increased SV+SI PGI2 release twofold to threefold compared with sham animals (p less than 0.01), which was abolished after blood reperfusion. SMA blood flow was decreased by 79.6% +/- 3.3% and 88.2% +/- 1.4% in the SK30 + R and SK45 + R groups compared with the sham animals (p less than 0.01). Superoxide dismutase treatment restored both SV+SI release of PGI2 after SK and SMA blood flow to control levels. CONCLUSION: Oxygen-derived free radicals locally produced during SK30 + R and SK45 + R inhibited splanchnic PGI2 synthesis, which contributed to decreased splanchnic blood flow. PMID- 1641775 TI - Cytokine regulation of gut ornithine decarboxylase gene expression and enzyme activity. AB - BACKGROUND: The enzyme ornithine decarboxylase (ODC) catalyzes the rate-limiting step in polyamine biosynthesis and is important for gut mucosal repair after systemic injury (e.g., burns); however, the mechanisms responsible for the injury mediated induction of ODC are not known. The purpose of this study was to determine whether interleukin-1 (IL-1) or tumor necrosis factor (TNF), which are released immediately after injury, regulates gut mucosal ODC enzyme activity and gene expression. METHODS: In vivo: In experiment 1, 64 male BALB/c mice received either recombinant IL-1 beta (2 x 10(4) units/kg administered intraperitoneally) or saline solution. In experiment 2, 64 mice received either recombinant TNF alpha (100 micrograms/kg administered intraperitoneally) or saline solution. We determined ODC enzyme activity and ODC mRNA levels in small intestine and kidneys at 2, 4, 12, and 24 hours after injection. In vitro: We also determined the ODC enzyme activity in intestinal epithelial crypt cells after either IL-1 beta or TNF-alpha treatment. RESULTS: IL-1, but not TNF, increased small intestinal ODC enzyme activity. In addition, IL-1 increased ODC enzyme activity in intestinal epithelial crypt cells at 5 and 6 hours after treatment. Both IL-1 and TNF increased small intestinal ODC mRNA levels. Neither agent affected ODC enzyme activity or ODC mRNA levels in the kidney. CONCLUSIONS: These results suggest that the cytokine-mediated induction of ODC in the small intestine is tissue specific, that the induction occurs at multiple cellular levels, and that ODC may play a vital role in the restoration of gut mucosa that occurs after injury. PMID- 1641776 TI - Induction of donor-specific tolerance to rat cardiac allografts by intrathymic inoculation of bone marrow. AB - BACKGROUND: Induction of donor-specific tolerance to tissue or organ allografts can readily be achieved by administration of allogeneic bone marrow to neonatal rodents; however, in adult recipients induction of transplantation tolerance by this strategy generally requires intensive cytoablative conditioning. Described here is a novel method of promoting transplantation tolerance that involves inoculation of donor bone marrow into the thymus of transiently immunosuppressed adult recipients. METHODS: Prospective Wistar-Furth recipients were inoculated with allogeneic Lewis bone marrow cells (BMCs) either intrathymically or intravenously in conjunction with a single dose of antilymphocyte serum 2 to 3 weeks before receiving donor-strain cardiac allografts. Recipients were monitored for graft survival and examined for presence of hematopoietic chimerism. RESULTS: Intrathymic but not intravenous inoculation of donor BMCs led to permanent survival of donor-strain cardiac allografts, whereas third-party Dark agouti cardiac allografts were rejected promptly. Persistence of donor chimerism was demonstrated in the thymus of Wistar-Furth recipients of intrathymic Lewis BMCs for as long as 3 weeks after BMC inoculation. CONCLUSIONS: Intrathymic inoculation of BMCs concurrently with a single dose of antilymphocyte serum induces donor-specific unresponsiveness to rat cardiac allografts. The unresponsiveness may be the result of deletion or functional inactivation of alloreactive clones maturing in a thymus bearing donor alloantigen. Intrathymic inoculation of BMCs deserves further evaluation as a possible clinical strategy for the induction of transplantation tolerance. PMID- 1641777 TI - Stimulation of hepatocyte System y(+)-mediated L-arginine transport by an inflammatory agent. AB - BACKGROUND: Arginine participates in several distinct metabolic pathways, including polyamine and nitric oxide biosynthesis. Normally, arginine is effectively sequestered from the hepatocyte intracellular space by the low basal activity of membrane transport system y+. This has implications for the subsequent metabolism of arginine and for hepatic arginine requirements during a septic insult. We investigated the influence of tumor necrosis factor (TNF) on the activity of System y(+)-mediated hepatocyte arginine transport employing hepatic plasma membrane vesicles (HPMVs). METHODS: Rats were treated with a single intraperitoneal injection of TNF (50 or 150 micrograms/kg body weight) for 2, 4, or 24 hours, and HPMVs were prepared by Percoll density gradient centrifugation. Vesicle purity was established by assay of enzyme markers. Vesicle arginine transport activity was evaluated by measurement of tritiated arginine uptake employing a rapid mixing-filtration technique. RESULTS: Arginine transport by HPMVs was entirely independent of sodium and consisted of saturable and nonsaturable components. Prior treatment with TNF resulted in a time- and dose-dependent stimulation of saturable transport within 2 hours and a return to basal levels after 24 hours. Nonsaturable uptake was unchanged. Inhibition analysis indicated that the TNF-induced increase in saturable arginine transport activity was mediated by an increase in System y+. Kinetic analysis revealed that accelerated transport was caused by a 78% increase in the maximal velocity of transport without alteration in transport affinity. CONCLUSIONS: In vivo treatment with TNF results in a rapid stimulation of saturable, System y(+) mediated arginine transport in the liver. This TNF-induced stimulation of hepatic arginine transport may serve to increase the normally restricted availability of extrahepatic arginine to the hepatocyte intracellular space during a septic insult to support important arginine-dependent pathways in the liver. PMID- 1641778 TI - Experience as a surgeon determines resident knowledge. AB - BACKGROUND: This is a prospective study that compares operative experience with performance on the American Board of Surgery Inservice Training Examination (ABSITE) to establish the primacy of procedural experience in the graduate training environment. METHODS: Operative experience was determined from a computerized log of surgical procedures. The Report D of the 1991 ABSITE was used to assign each test item to specific operative procedures and to determine the frequency of the correct response (Fcr) for each item. The fraction of operative procedures (Fs) was determined for each category of surgical procedures (Fs = Number of procedures as surgeon/Total number of procedures). The Fcr was compared to the Fs by use of the Pearson correlation coefficient with significance at 95% confidence. RESULTS: Forty-two residents reported doing 8357 surgical procedures as surgeon in 12 months. Report D contained 209 test items. Of these, 162 items could be assigned to 26 categories of surgical procedures. The Fcr correlated directly with the Fs (p = 0.002, r = 0.605). CONCLUSIONS: A significant correlation exists between the experience of surgical residents as surgeon and their performance on the ABSITE: PMID- 1641779 TI - The effect of erythropoietin in normal healthy volunteers and pediatric patients with burn injuries. AB - BACKGROUND: Surgical procedures result in blood loss that can require replacement transfusions. Such therapy may result in multiple adverse sequelae, including transmission of infectious diseases and immune impairment. Alternative therapies are therefore desirable. METHODS: We evaluated the ability of recombinant human erythropoietin (rEPO) to increase red blood cell production in both normal healthy volunteers and patients with burn injuries. The effect of rEPO on immune function in the volunteers was also evaluated. The volunteers received 150 units/kg rEPO daily for 7 days, with immune function and hematopoiesis assayed on days 0, 7, and 14. The patients with burn injuries received either 500 units/kg/day rEPO with iron supplementation or merely the iron. RESULTS: rEPO increased erythropoiesis in both the volunteers and the patients with burn injuries. Failure to provide iron supplementation to the volunteers resulted in significant depletion of iron stores with a concomitant impairment in immune function that paralleled the iron depletion. CONCLUSIONS: rEPO therapy offers the potential to increase red blood cell production in surgical patients. Failure to provide iron supplementation in patients receiving rEPO can lead to a rapid depletion of iron stores and may contribute to an immune dysfunction. PMID- 1641780 TI - Antihemostatic and antithrombotic effects of monoclonal antibodies against von Willebrand factor in nonhuman primates. AB - BACKGROUND: Because the adhesive glycoprotein von Willebrand Factor (vWF) mediates initial platelet attachment at sites of vascular injury and may also contribute to shear-dependent platelet thrombus formation, we have determined in vivo the relative antithrombotic efficacy and hemostatic safety of infusing murine monoclonal antibodies against vWF. METHODS: In baboons with chronic arteriovenous shunts, thrombus formation was initiated by interposition of thrombogenic Dacron vascular grafts (VG) and endarterectomized baboon aortic segments (EAS). Thrombus formation on VG and EAS was assessed by use of real-time scintillation camera imaging of indium 111-labeled platelet deposition. In control and treated animals (anti-vWF antibody) platelet hemostatic competence was evaluated by means of serial measurements of platelet count, bleeding time, and ex vivo platelet aggregation in response to adenosine diphosphate and ristocetin. RESULTS: Although bolus antibody infusions did not affect circulating platelet counts, bleeding times were immediately prolonged to 28 +/- 4 minutes (vs 4.7 +/- 0.4 minutes before treatment, p = 0.01). Bleeding times normalized within 24 hours after antibody administration. Platelet aggregation in response to adenosine diphosphate was unchanged by antibody therapy, whereas ristocetin induced platelet aggregation was abolished acutely and remained impaired for 24 hours. Platelet deposition on VG after 60 minutes of exposure to flowing blood was 2.95 +/- 0.74 x 10(9) platelets/cm in six control animals as compared to 1.86 +/- 0.16 x 10(9) platelets/cm in five treated animals (p = 0.04). Similarly, platelet deposition on EAS averaged 4.40 +/- 0.89 x 10(9) platelets/cm in control studies and was reduced significantly by antibody therapy (1.52 +/- 0.50 x 10(9) platelets/cm, p = 0.02). CONCLUSIONS: Despite profound interruption of platelet hemostatic functions, therapeutic targeting of vWF modestly inhibits platelet dependent thrombosis. PMID- 1641781 TI - Oral vitamin E prophylaxis in the protection of newborn myocardium from global ischemia. AB - BACKGROUND: Oxygen-derived free radicals have been implicated in the pathophysiology of myocardial reperfusion injury after ischemic insult. Recent studies have demonstrated that free radical scavengers could afford protection to the mature myocardium from these injuries. The purpose of this study was to investigate whether oral vitamin E pretreatment could improve the tolerance of newborn hearts to ischemia. METHODS: Two groups of six newborn piglet hearts were randomly studied in an isolated, perfused Langendorff heart model. Group I control hearts were subjected to 30 minutes of cold perfusion at 15 degrees C, in which profound hypothermia was achieved over a period of 10 minutes. This was followed by 90 minutes of global ischemia arrest and 30 minutes of normothermic reperfusion. Group II piglets were pretreated with d-alpha-tocopherol (vitamin E) given by oral gavage for 4 days before similar experimentation. Baseline functional parameters were recorded before cold perfusion by a left intraventricular balloon inflated to a diastolic pressure of 11 to 14 mm Hg and repeated at the end of 30 minutes of normothermic reperfusion. Creatine phosphokinase leakage in the perfusate was analyzed immediately after reperfusion and the pressure/volume ratio was obtained at the conclusion of each experiment. RESULTS: Postischemic functional recovery of vitamin E-pretreated group II hearts was improved significantly compared with the control hearts (group I). Left ventricular diastolic pressure was 87.5% +/- 2.3% versus 66.1% +/- 2.3%, +dp/dt was 94.5% +/- 2.2% versus 68.0% +/- 5.6%, -dp/dt was 93.0% +/- 2.4% versus 69.6% +/- 6.0%, mean left ventricular end-diastolic pressure was 13.0 +/- 0.8 versus 22.0 +/- 3.5 mm Hg, and pressure/volume ratio was 29.2 +/- 2.3 versus 41.8 +/- 4.3 mm Hg/ml, respectively (p less than 0.05). Perfusate creatine phosphokinase leakage was also reduced significantly from 112.5 +/- 17.9 to 56.2 +/- 4.0 IU/L (p less than 0.05) in group II. CONCLUSIONS: Oral vitamin E pretreatment improved the ischemic tolerance of newborn myocardium and therefore might be considered a valuable, effective, and inexpensive method of myocardial protection. PMID- 1641782 TI - Mechanism of the beneficial effects of pentoxifylline on hepatocellular function after trauma hemorrhage and resuscitation. AB - BACKGROUND: The purpose of this study was to determine whether pentoxifylline administration restores the depressed hepatocellular function after trauma hemorrhage and crystalloid resuscitation and, if so, whether this is the result of the down-regulation of inflammatory cytokines, tumor necrosis factor (TNF) and interleukin-6 (IL-6). METHODS: After laparotomy rats were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of maximum shed blood volume was returned in the form of Ringer's lactate. They were then resuscitated with Ringer's lactate to four times the shed blood volume. Pentoxifylline (50 mg/kg body weight) or saline solution was infused intravenously for 95 minutes during and after resuscitation. One and a half hours and 4 hours after resuscitation, hepatocellular function (maximal velocity [Vmax] and the efficiency of the active transport [Km] of indocyanine green clearance) and plasma. TNF and IL-6 levels were determined with in vivo hemoreflectometer and cellular assays, respectively. RESULTS: Circulating TNF and IL-6 levels increased significantly after hemorrhage and resuscitation. Pentoxifylline treatment, however, markedly decreased the levels of these cytokines, and the values were similar to those of sham rats. The decreased Vmax and Km values were also restored by pentoxifylline treatment. Moreover, there was a significant correlation between Vmax and TNF or IL-6 levels. CONCLUSIONS: The down-regulation of inflammatory cytokines by pentoxifylline may be the mechanism by which this agent restores the depressed hepatocellular function after trauma hemorrhage and resuscitation. PMID- 1641783 TI - Triiodothyronine treatment maintains surfactant synthesis during sepsis. AB - BACKGROUND: Pulmonary compromise with altered surfactant metabolism is frequently noted during sepsis; triiodothyronine is necessary for normal surfactant synthesis. We evaluated the role of physiologic replacement of triiodothyronine during sepsis-induced hypothyroidism on surfactant synthesis and lung structural integrity. METHODS: Male Sprague Dawley rats (average weight, 330 gm) underwent sham laparotomy or cecal ligation and puncture; treatment was administered to rats that underwent cecal ligation and puncture by Alzet osmotic pump consisting of triiodothyronine (3 ng/hr) or saline control. The rats were killed 24 hours after serum triiodothyronine determination by radioimmunoassay (normal, 60 to 160 ng/dl). Surfactant was obtained by saline lavage. Lipid content was determined by Folch extraction; phospholipid content was verified by chromatography. Blinded histologic analysis of lung confluence and alveolar sparing was done in separate subgroups. Results are +/- SE. RESULTS: Control rats with sepsis were hypothyroid at 24 hours; rats given triiodothyronine were euthyroid (rats that underwent sham laparotomy, 67.7 +/- 4.9 ng/dl; control rats, 37.6 +/- 5.7 ng/dl; and triiodothyronine, 85.7 +/- 19 ng/dl; p less than 0.05 compared with triiodothyronine by analysis of variance). Surfactant production was significantly improved by triiodothyronine compared with control (60.7 +/- 22.6 mg vs 23.2 +/- 11.3 mg; p less than 0.05 by analysis of variance). Lung histologic integrity was maintained by triiodothyronine treatment during sepsis. CONCLUSIONS: Triiodothyronine supplementation may be beneficial in septic-induced pulmonary dysfunction. PMID- 1641784 TI - Passive immunization against tumor necrosis factor inhibits interleukin-2-induced microvascular alterations and reduces toxicity. AB - BACKGROUND: Antineoplastic therapy with interleukin-2 (IL-2) has been limited by dose-dependent systemic toxicities. Previous studies suggest that the hemodynamic instability and "vascular leak syndrome" that develop immediately after IL-2 administration occur secondary to neutrophil-mediated events in the microcirculation. Because IL-2 has limited direct effects on neutrophils and acutely induces the production of tumor necrosis factor-alpha (TNF), we hypothesized that the acute microvascular alterations and hemodynamic instability induced by IL-2 were mediated by TNF. METHODS: The cremaster muscles of anesthetized rats were prepared for intravital microscopy. All animals were injected with fluorescein isothiocyanate conjugated to bovine serum albumin, and relative interstitial fluorescence was quantitated as an index of macromolecular leakage. Vital signs, leukocyte-endothelial interactions, and interstitial fluorescence were quantitated every 30 minutes for 2 hours after intravenous injections of IL-2, TNF, and IL-2 with polyclonal antibody to TNF. RESULTS: Both IL-2 and TNF acutely induced hypotension, tachycardia, increased macromolecular leakage, and increased leukocyte-endothelial adherence. Polyclonal antibody to TNF effectively inhibited IL-2-induced leukocyte-endothelial adherence, macromolecular leakage, and hypotension. CONCLUSIONS: These data suggest that the acute microvascular alterations and hypotension induced by IL-2 are mediated by TNF. PMID- 1641785 TI - [WHO: support program to Eastern countries]. PMID- 1641786 TI - [Open your eyes!]. PMID- 1641787 TI - [Women's Day--infant girls in danger of dying]. PMID- 1641788 TI - [SEF (Joint Council of Student Nurses)--we need illness days compensation]. PMID- 1641789 TI - [SEF--70 percent fail. Interview by Lars Peter Bergqvist]. PMID- 1641790 TI - [Substance abuse--it is also the responsibility of the place of work]. PMID- 1641791 TI - [Substance abuse--confrontation, contract and professional support. Interview by Mette Fjordbo]. PMID- 1641792 TI - [Substance abuse: alcohol policy--a personnel benefit]. PMID- 1641793 TI - [Child psychiatry--the necessary daily routine]. PMID- 1641794 TI - [Child psychiatry--it involves the entire family]. PMID- 1641795 TI - [Child psychiatry--act punctually and honestly]. PMID- 1641796 TI - [Child psychiatry--to understand Kim]. PMID- 1641797 TI - [Child psychiatry--when Uffe stopped eating]. PMID- 1641799 TI - [Child psychiatry--force feeding]. PMID- 1641798 TI - [Child psychiatry--my daughter is trying to starve herself to death]. PMID- 1641800 TI - [Child psychiatry--nurses get emotionally involved]. PMID- 1641801 TI - [Terminal care at home]. PMID- 1641802 TI - [Greenland--health project in a waiting position]. PMID- 1641803 TI - [Greenland--more services for half the money. Interview by Soren Palsbo]. PMID- 1641804 TI - [Child psychiatry--what is going on in their heads?]. PMID- 1641805 TI - [Child psychiatry--disturbed contact]. PMID- 1641806 TI - Maternal factors affecting teratogenic response: a need for assessment. AB - A review of current literature suggests that maternal nutritional status can be an important modulator of the developmental toxicity of a number of agents in the environment. While the provision of multivitamin/multimineral supplements during the periconceptional period is often associated with improved pregnancy outcome, it has been difficult to identify specific nutrient deficiencies as causative factors of abnormal development in humans. One explanation for this is that nutrient deficiencies can arise through a number of means in addition to a simple dietary deficit of the nutrient. The hypothesis is proposed that one mechanism contributing to the embryotoxicity of a diverse group of insults is an alteration in the metabolism of select nutrients. Evidence is presented that zinc is one nutrient whose metabolism can be markedly influenced by a variety of insults. One consequence of this alteration can be a reduction in embryonic zinc uptake, the development of embryonic zinc deficiency and abnormal development. PMID- 1641807 TI - Diagnosis of abnormalities of the human fetus during the first, second, and third trimesters. AB - Clinical teratologists will have new challenges during the 1990s as birth defects are diagnosed more frequently than in previous decades. Malformations and genetic disorders will be diagnosed in utero during all three trimesters of pregnancy. The teratologist may participate in or lead a multispecialty group to give the involved family optimal interpretation of test results, counseling, and recommendations regarding subsequent clinical management. PMID- 1641808 TI - In vitro approaches to the elucidation of mechanisms of chemical teratogenesis. AB - This article describes some of the contributions that in vitro methods have made to our progress, albeit slow, toward understanding mechanisms of chemical teratogenesis. Emphasis is given to the painstaking and time consuming nature of approaches required to elucidate mechanisms. The examples considered are cyclophosphamide, 2-methoxyethanol, and retinoids. Some of the newer methods that take advantage of the recent advances in molecular biology and analytical chemistry have already been applied to studies on teratogenic mechanisms. Prospects for the 1990s are excellent and promise more rapid progress than during the past decade toward unraveling the mysteries of normal developmental biology. That knowledge in turn should be immediately applicable for investigations on developmental toxicant-induced abnormal development. PMID- 1641809 TI - Clinical teratology counseling and consultation case report: exposure to diagnostic radiation early in pregnancy. PMID- 1641810 TI - Teratogenic Agent Information Centre: fifteen years of counseling and pregnancy follow-up. AB - The Teratogenic Agent Information Centre was set up 15 years ago in response to a growing demand from a medical profession struggling to cope with the problem of teratogenic risk. Our goal was to provide information on the real nature of the risk and to monitor all at-risk pregnancies so as to obtain data in a field where there are still, unfortunately, many gaps in our knowledge. The results of these 15 years have been most encouraging, in that physicians have been provided with specialized information and the follow-up of gestations had provided considerable clinical data, which has contributed to advancing our understanding in this domain. PMID- 1641811 TI - Fetal dexamethasone exposure alters macromolecular characteristics of rat brain development: a critical period for regionally selective alterations? AB - Fetal glucocorticoid exposure retards postnatal growth and evokes abnormalities of nervous system structure and function. To examine the underlying mechanisms, we administered 0.2 or 0.8 mg/kg of dexamethasone to pregnant rats on gestational days 17, 18, and 19 and assessed brain region cell development with indices of DNA content (total cell numbers), DNA concentration (cell packing density), and protein/DNA ratio (relative cell size). Dexamethasone evoked deficits of pup body and brain region weights, but the brain regions displayed growth-sparing associated initially with preservation of cell numbers (normal or elevated DNA content and concentration), at the expense of relative cell size (decreased protein/DNA). Subsequently, brain cell acquisition lagged behind that of controls, with deficits in DNA and elevations of protein/DNA. In midbrain + brainstem and in cerebellum, cell markers returned to normal by weaning. However, the forebrain showed persistent elevations of DNA and reduced protein/DNA, indicative of replacement of neurons with glia. Because the treatment period coincided with the timing of neuronal cell replication in the forebrain, but not in the other regions, these results suggest that the critical period for lasting deficits of dexamethasone coincides with the peak of neuronal mitosis. PMID- 1641812 TI - Toxicity of the methyl isocyanate metabolite S-(N-methylcarbamoyl)GSH on mouse embryos in culture. AB - Methyl isocyanate, the chemical involved in the 1984 accident at Bhopal, India, forms a labile conjugate, S-(N-methylcarbamoyl)GSH (SMG), by way of a reversible reaction with GSH. We studied the toxicity of SMG on mouse embryos explanted on day 8 of gestation and cultured in rat serum for 42 hr. SMG caused concentration dependent decreases in growth and development over the range 0.1-2 mM, without causing significant mortality. At a concentration of 2 mM, SMG completely arrested embryo development, but heartbeat was absent in only one of nine embryos at 42 hr. At a concentration of 0.25 mM, SMG reduced embryo size to 75% and protein content to 63% of the control; 18% of embryos failed to rotate. At this concentration (0.25 mM), which was selected for all other studies, spinal kinks and somite pair distortion in the region of the forelimb were evident in 38% of embryos; no other abnormalities were noted. DNA content of and thymidine incorporation by embryos and yolk sacs was reduced by SMG, although this was more pronounced in the yolk sac than in embryos. At subtoxic concentrations, the L cysteine precursor (-)-2-oxo-4-thiazolidine-carboxylic acid did not, but GSH did, inhibit embryotoxicity of SMG. It is concluded that SMG exerts embryotoxic and dysmorphogenic effects and may contribute to systemic toxicity of methyl isocyanate. PMID- 1641813 TI - Interpretation of recurring weak associations obtained from epidemiologic studies of suspected human teratogens. AB - Epidemiological studies of suspected human teratogens not infrequently lead to recurring weak or moderate associations (relative risks or odds ratios ranging from greater than 1 to 3 for adverse effects and from 1/3 to less than 1 for protective effects) between specific defects and prenatal exposures. Examples of such associations include cigarette smoking and oral clefts (odds ratios between 1 and 2) and periconceptional multivitamin/folic acid supplementation and neural tube defects (odds ratios from 1/3 to 1). In this paper, we illustrate that low relative risk recurring in well-designed studies may reflect underlying biologic mechanisms and should not be readily dismissed. Low relative risks could be the result of a combination of the following factors: 1) unmeasured confounding, 2) exposure misclassification (often related to the inability to pinpoint relevant dose and timing), 3) outcome misclassification (related to the etiologic heterogeneity of birth defects), 4) biologic interactions (related to teratogenic effects in population subgroups defined by genetic susceptibility or the presence of other exposures), and 5) differential prenatal survival (related to the combined impact of the exposure and the defect on prenatal survival). These issues can be addressed in epidemiologic studies by using biological markers of exposure and susceptibility, dysmorphologic evaluation of affected infants, subgroup analysis for etiologic heterogeneity, a search for biologic interactions, and the use of prospective cohort studies. Finally, low relative risks in the face of common exposures can reflect an important public health contribution of the exposure to the occurrence of the defect in the population. PMID- 1641814 TI - Long bone development in extrinsic fetal akinesia: an experimental study in rat fetuses subjected to oligohydramnios. AB - The transverse growth of long bones during intrauterine development was studied in rat fetuses subjected to experimental oligohydramnios in order to determine whether the skeletal changes, if any, in extrinsic fetal akinesia were similar to those observed in curarized rat fetuses with the fetal akinesia deformation sequence. Oligohydramnios was induced by daily extraction of amniotic fluid from day 17 of gestation until term. Experimental fetuses were compared with a sham operated control group. The total area and perimeter, the absolute and relative amount of periosteum and bone trabeculae, the major and minor axes, and the elongation factor were measured in histological cross sections of the femoral metaphysis and diaphysis with an IBAS 1 image analysis system. Rat fetuses in the experimental group showed multiple articular contractures, redundant skin, and lung hypoplasia, a phenotype consistent with the oligohydramnios sequence. No alterations in femoral shape and transverse growth of the metaphysis and diaphysis were noted in these fetuses. These results suggest that the main mechanical factor related to fetal bone modeling is muscular strength, while motion would be mainly involved in fetal joint development. PMID- 1641815 TI - In vitro exposure of preimplantation mouse embryos to cocaine and benzoylecgonine inhibits subsequent development. AB - Cocaine is used by over 20% of women of reproductive age. Although there have been numerous studies focusing on its effects on reproductive processes, none has evaluated its direct effect on preimplantation development. We have investigated the effect of cocaine and its major metabolite, benzoylecgonine, on in vitro preimplantation mouse embryogenesis. One-cell embryos were exposed at the one-, two-, four-, or eight-cell stage for 24 hr to medium containing 0-400 micrograms/ml cocaine or benzoylecgonine and then cultured to the blastocyst stage. Cocaine had its strongest inhibitory effect at the earliest stages of development. At the one- and two-cell stages, there was a significant inhibition of blastocyst formation following exposure to cocaine concentrations of 25-400 micrograms/ml, and at the four-cell stage there was an inhibitory effect at 100 and 400 micrograms/ml cocaine. Benzoylecgonine inhibited the development of embryos to blastocyst only at the one- and two-cell stages, at concentrations of 100-400 micrograms/ml. These findings suggest that cocaine is capable of blocking preimplantation embryogenesis, particularly following exposure at the earliest stages, and that this toxicity may abate as cocaine is biotransformed to benzoylecgonine. PMID- 1641816 TI - Morphological and physiological correlates of unilateral agenesis of the urogenital system in young ovariectomized ACI rats. AB - ACI rats are distinguished by a polygenic trait resulting in unilateral agenesis of the urogenital system in 20-30% of animals of both sexes. This report details additional features, both morphological and physiological, which distinguish ACI rats with unilateral agenesis of the reproductive and urinary tracts from the majority of ACI rats that have intact urogenital systems. Young female ACI rats were ovariectomized at 34 days of age and sacrificed 19 days later. A preliminary determination of the urogenital morphology was made at the time of ovariectomy and then confirmed by careful abdominal inspection at necropsy. Data on the time of vaginal opening were obtained at selected intervals prior to sacrifice. At necropsy, the mammary glands were removed and were prepared as stained whole mounts for morphological evaluation; the remaining portions of the reproductive tracts were excised, weighed, fixed, and sectioned for microscopic examination. A majority of animals with unilateral agenesis had mammary glands that had higher degrees of glandular proliferation than the mammary glands of intact rats. Unilateral agenesis animals also possessed significantly thicker and heavier uterine horns, despite having been ovariectomized. Furthermore, rats with unilateral agenesis were found to have an earlier time of vaginal opening than that of their intact counterparts. These features of ovariectomized ACI rats with unilateral agenesis are consistent with an active, extra-ovarian source of endogenous estrogen. Further investigation of the endocrinological state of animals with unilateral agenesis of the urogenital tract is warranted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641817 TI - Hirudin C-terminal fragments inhibit thrombin induced neutrophil chemotaxis. AB - Since native hirudin blocks the thrombin induced chemotaxis response of neutrophils, we examined whether hirudin C-terminal peptides were also capable of this inhibition. The studies showed that thrombin induced human neutrophil chemotaxis was effectively blocked by the C-terminal hirudin peptide analogs, Gly Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-Gln (12-mer[54-65]) and Thr-Pro-Lys-Pro Gln-Ser-His-Asn-Asp-Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu- Tyr- Leu-Gln (21-mer[45 65]). Furthermore, neither peptide had an effect on formyl-L-methionyl-L-leucyl-L phenylalanine induced chemotaxis. The results suggest that binding of the hirudin C-terminal peptides block the thrombin chemotactic domain. PMID- 1641818 TI - Hematological causes of venous thrombosis in young people: high incidence of myeloproliferative disorder as underlying disease in patients with splanchnic venous thrombosis. AB - Thrombotic events occur frequently in myeloproliferative disorders, namely polycythaemia vera and essential thrombocythaemia. Standard diagnostic criteria are designed quite stringent, so that a number of patients could be underdiagnosed. Spontaneous erythroid colonies formation from bone marrow or peripheral blood in the absence of exogenous erythropoietin is considered a reliable index of myeloproliferative disorder even at early stages. Endogenous erythroid colonies (EECs) formation was assessed in 43 patients having recently suffered from venous thrombosis prior to 45 years and without a previous diagnosis of hematological disease favouring thrombosis. A screening for coagulative abnormalities associated with thrombophilia was also carried out: in 5 patients (11.6%) a plasmatic thrombogenic defect was found (quantitative deficiency of antithrombin III, 1 case, protein C, 2 cases, protein S, 1 case, and plasminogen, 1 case). In 10 patients (2 males and 8 females) (23.2%) EECs assay was positive, allowing diagnosis of myeloproliferative disease even though 7 of them did not fulfill standard diagnostic criteria. In the other 3 patients who met the criteria for diagnosis of overt myeloproliferative disease the thrombotic event was the inaugural manifestation. In all these EECs-positive patients thrombosis involved mesenteric and portal veins (n = 4), hepatic veins (n = 3), portal vein (n = 2), mesenteric vein (n = 1). One of them was simultaneously affected from congenital protein C deficiency. Thus latent or atypical forms of myeloproliferative disease as well as the overt stages were the most frequent recognized cause of splanchnic venous thrombosis, accounting for 55% of the cases of our series. On the contrary no EECs-positive subject was found among the 25 patients with other sites of thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641819 TI - Experimental carotid stenosis and endothelial injury in the rabbit: an in vivo model to study intravascular platelet aggregation. AB - Previous studies have shown that experimental canine coronary artery stenosis associated with endothelial injury results in a typical pattern of coronary flow characterized by gradual decreases in coronary flow to almost zero values followed by restorations of flow to normal values. This pattern of flow, called cyclic flow reductions (CFRs), is the consequence of recurrent platelet aggregation at the site of the stenosis and endothelial injury and subsequent dislodgement of the thrombus. In the present study, platelet activation and aggregation in vivo was induced by placing an external constrictor around carotid arteries with endothelial injury in anesthetized rabbits. Carotid blood flow velocity was measured continuously with a Doppler flow probe positioned proximally to the constrictor. After placement of the constrictor, CFRs developed in 14 of 14 rabbits with a mean frequency of 16.5 +/- 2.3 cycles/h. CFRs were observed for 30 min, and the animals were treated with either an i.v. bolus of aspirin (10 mg/kg) or R 68070 (20 mg/kg), a drug with simultaneous TxA2 synthase and TxA2/PGH2 receptor blocking properties. Aspirin completely inhibited CFRs in 4 of 7 rabbits, whereas R 68070 eliminated CFRs in 7 of 7 animals. In the 3 animals that did not respond to aspirin, administration of ketanserin (0.25 mg/kg i.v.), a selective serotonin S2 receptor antagonist, completely abolished CFRs. Both aspirin and R 68070 resulted in a marked reduction in serum TxB2 formation and in a complete inhibition of ex vivo platelet aggregation in response to arachidonic acid, whereas aggregation in response to U46619, a TxA2 mimetic, was inhibited only in R 68070-treated rabbits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641820 TI - Double-blind, randomized comparison of systemic continuous infusion of 0.25 versus 0.50 mg/kg/24 h of alteplase over 3 to 7 days for treatment of deep venous thrombosis in heparinized patients: results of the European Thrombolysis with rt PA in Venous Thrombosis (ETTT) trial. AB - Thirty-two patients with acute, proximal-vein thrombosis were treated with heparin and alteplase (0.25 versus 0.5 mg/kg/24 h during 3-7 days) in a randomized, double-blind, multicenter, European (ETTT) trial. The treatment resulted in a decrease of the venographic Marder's score from 18 (6-25) to 13 (2 24) units (median, range) in Group I (0.25 mg/kg/24 h, n = 15, median decrease 3.0, p = 0.32) and from 17.5 (3-33) to 15.5 (0-27) in Group II (0.5 mg/kg/24 h, n = 16, median decrease 4.0, p = 0.23). Comparison of the sequential venograms could be performed in 14 cases of Group I and in 15 cases in Group II. A minority of patients showed substantial partial recanalization of the initially obstructed veins on the control venogram (one in each treatment group) and most of the control venograms showed either thrombus size reductions (5 in Group I, 7 in Group II) or no change or even deterioration (8 in Group I, 7 in Group II). Major bleedings were observed in 7 patients (7/32, 22%), 5 of them occurring in Group II (5/17, 29%). Thus, the results of the ETTT trial show that the used low dosages of alteplase administered intravenously over 3-7 days in heparinized patients cannot be recommended as a treatment for patients with deep venous thrombosis of lower limbs and/or pelvis. Further studies are needed to define a more suitable dosage regimen of alteplase in this indication. PMID- 1641821 TI - Production and therapeutic use of a factor XI concentrate from plasma. AB - Factor XI deficiency is an uncommon bleeding disorder usually manifested by excessive bleeding after surgery or trauma. Until recently the only effective therapy has been fresh-frozen plasma (FFP) infusion. We describe the efficacy and safety of a new factor XI concentrate produced from human donor plasma by a modification of the method used for antithrombin III concentrate. The mean recovery of factor XI in the circulation measured on 62 occasions was approximately 91% of the injected dose, and the mean half-disappearance-time was 52 h. The concentrate was used for 31 invasive procedures in 30 patients, including 16 patients who had a definite bleeding tendency on previous occasions, with normal haemostasis being achieved in all but 1. Only 1 patient (previously experiencing allergy to FFP) experienced adverse effects during infusion. Monitoring of liver function tests and viral antibody status in suitable patients has shown no evidence of transmission of hepatitis viruses, HIV-1 or parvovirus B19. We conclude that this concentrate provides effective treatment for patients with factor XI deficiency. Preliminary results suggest safety from virus transmission, but this needs to be established in further studies of previously untreated patients. PMID- 1641822 TI - Absence of the largest platelet-von Willebrand multimers in a patient with lactoferrin deficiency and a bleeding tendency. AB - We have studied a young male with lactoferrin deficiency and a bleeding tendency responsive to cryoprecipitate. This child has had increased bleeding following surgical procedures and a variably prolonged template bleeding time. The patient has a normal platelet count, normal in vitro platelet ATP secretion and aggregation in response to a variety of agonists, and normal concentration of plasma-von Willebrand factor ristocetin cofactor activity and antigen. Analysis of plasma-vWf multimers by agarose gel electrophoresis consistently demonstrated a subtle decrease in the largest vWf multimers. In contrast, analysis of the patient's platelet-vWf revealed normal vWf:Ag, decreased vWf ristocetin cofactor activity, and a striking absence of the high and intermediate size molecular weight vWf multimers. Analysis of surface bound platelet-vWf demonstrated normal amounts on the surface of unstimulated platelets, but after thrombin stimulation the platelet-vWf surface expression did not increase. This lack of increased platelet-vWf surface expression resulted from decreased binding of secreted platelet-vWf to be surface of stimulated platelets. These data suggest that the patient's bleeding tendency may be related to a defect in his platelet-vWf structure and/or mobilization. This case represents a unique demonstration of an abnormality of platelet-vWf in the presence of normal plasma-vWf, and supports the data indicating an important role for platelet-vWf in primary hemostasis. PMID- 1641823 TI - In vitro inhibition of blood coagulation by tripeptide aldehydes--a retrospective screening study focused on the stable D-MePhe-Pro-Arg-H.H2SO4. AB - A series of peptide aldehydes synthetized in our institute during the last 15 years were screened to detect their inhibitory effect on blood coagulation. Simple conventional clotting assays, platelet function tests and fibrinolytic methods were used to evaluate the inhibitory potency of the compounds in complex clotting systems as well as their supposed antifibrinolytic effect in vitro. Special attention was paid to the possible interactions with blood cells and plasma proteins, and to the functional stability of the inhibitors in several tissue homogenates. D-Phe-Pro-Arg-H (GYKI-14166, RGH-2958), Boc-D-Phe-Pro-Arg-H (GYKI-14451) and D-MePhe-Pro-Arg-H (GYKI-14766) were found to be the most potent inhibitors. The peptide aldehydes via formation of reversible complexes with thrombin impede the enzyme to react with the coagulation factors, platelet membrane and vessel wall. The compounds inhibit platelet aggregation induced by thrombin specifically without changing the sensitivity of platelets to other inducers. D-Phe-Pro-Arg-H and D-MePhe-Pro-Arg-H showed no antifibrinolytic effect. D-MePhe-Pro-Arg-H and Boc-D-Phe-Pro-Arg-H proved to be stable in dry state for years and in solution at room temperature for several days. The anticoagulant activity of the compounds was declared in NIH antithrombin units. PMID- 1641824 TI - Cell shape change and cytosolic Ca2+ in human umbilical-vein endothelial cells stimulated with thrombin. AB - We quantified thrombin-induced endothelial cells shape change and investigated the role of Ca2+ in such shape change. We used the fluorescent Ca2+ indicator, fura2, to measure both shape change as cell size and intracellular free Ca2+ ([Ca2+]i), in cultured human umbilical-vein endothelial cells (HUVEC). Thrombin induced concentration-dependent decreases in cell size (percentage of cell size at 6 min after stimulation with 0.01 U/ml, 0.1 U/ml, or 1 U/ml thrombin) was 90.1 +/- 1.5%, 78.1 +/- 2.4%, and 40.9 +/- 2.4%, respectively. Thrombin also increased [Ca2+]i in a concentration-dependent manner. Both depletion of extracellular Ca2+, and also the addition of W5, a calmodulin antagonist, inhibited thrombin induced size reduction. These results indicate an association between shape change and [Ca2+]i mobilization in human endothelial cells stimulated by thrombin. PMID- 1641825 TI - Toward gene therapy in haemophilia A: retrovirus-mediated transfer of a factor VIII gene into murine haematopoietic progenitor cells. AB - To study and evaluate the potential of the haematopoietic system as a target for gene therapy in haemophilia A, we have infected murine bone-marrow cells with a recombinant retrovirus encoding blood-coagulation factor VIII and the bacterial enzyme neomycin-phosphotransferase. After transplantation of the infected bone marrow into lethally irradiated mice, the presence of intact vector could be demonstrated in DNA isolated from individual haematopoietic progenitor-cell derived spleen colonies. About 8% of the spleen colonies were shown to contain the intact vector. Selection for resistance to the neomycin analogue G418 prior to transplantation specifically killed the uninfected bone-marrow cells and, as a result, over 90% of the spleen colonies contained the factor VIII vector. However, expression of factor VIII in vivo, either at the RNA or at the protein level could not be demonstrated. From these data we conclude that: 1) retroviral vectors can be used to transfer factor-VIII cDNA into haematopoietic progenitor cells; 2) the vector sequences are expressed immediately after integration; and 3) transcription of the vector is repressed in the progenitor-cell-derived cells. PMID- 1641826 TI - Rapeseed oil and sunflower oil diets enhance platelet in vitro aggregation and thromboxane production in healthy men when compared with milk fat or habitual diets. AB - In this highly controlled trial, 26 normolipidemic men (average age 28 years, range 18 to 60) were fed a baseline diet high in milk fat (MF) (fat 36% of energy, saturates 19%, monounsaturates 11%, polyunsaturates 4%), followed by a diet high in sunflower oil (SO) (fat 38% of energy, saturates 13%, monounsaturates 10%, polyunsaturates 13%) and another diet high in low erucic acid rapeseed oil (RO) (fat 38% of energy, saturates 12%, monounsaturates 16%, polyunsaturates 8%). All diets were mixed natural diets with the same cholesterol contents. The baseline milk fat diet was given for 14 days and the oil diets for 24 days in a blind cross-over design. The platelet in vitro aggregation (slope %/min) induced by 1, 2 and 3 microM ADP and collagen (25 micrograms/ml PRP) was highly significantly (p less than 0.001) increased after both oil diets when compared with the results from the milk fat diet. The aggregation pattern determined by threshold collagen concentration confirmed increased collagen sensitivity of the platelets after the rapeseed oil diet (p less than 0.001). The enhancement of platelet aggregation was associated with increased in vitro platelet thromboxane production after the oil diets vs. the milk fat diet (p less than 0.05 after the sunflower oil diet and p less than 0.001 after the rapeseed oil diet). PMID- 1641827 TI - In vivo anticoagulant and antiplatelet effect of D-Phe-Pro-Arg-H and D-MePhe-Pro Arg-H. AB - D-Phe-Pro-Arg-H and D-MePhe-Pro-Arg-H synthetized in our institute were administered to mice, rats, rabbits and beagle dogs. The kinetics of the anticoagulant and antiplatelet effect was recorded by measuring various clotting parameters, platelet count and aggregation, and evaluated as proposed by Verstraete and Verwilghen. The minimum effective doses were found to be 0.25-0.5 mg kg-1h-1 by intravenous continuous infusions and 0.5-1.0 mg/kg by single injections. The dose-dependent prolongation of clotting times appeared after application within minutes and returned to baseline values as a function of dose. Blood level of the inhibitors was determined by a bioassay. Unlike heparin, no higher starting dose was required to reach the anticoagulant threshold level, i.e. 0.03-0.1 microgram/ml whole blood. The peptides did not cause significant changes in platelet count and function or in hemodynamic parameters (blood pressure, heart rate and ECG) and in respiration. They blocked platelet aggregation induced by thrombin ex vivo specifically. No rebound effect or bleeding could be demonstrated even after subtoxic doses of the compounds. The onset of the anticoagulant and antithrombotic effect appeared within 60 min after single oral doses and lasted for 3-6 h. In close correlation with the anticoagulant effect a complete or significant inhibition of platelet aggregation induced by thrombin ex vivo could also be recorded by using 5-10 mg/kg doses. PMID- 1641829 TI - Thrombin activity by intrinsic activation of plasma in-vitro accelerates with increasing age of the donor. AB - Thrombotic diseases increase in incidence with advancing years and this might be partly due to an increased propensity for fibrin formation in older individuals. Accordingly we decided to investigate whether the time taken to generate 50% thrombin activity in vitro varied with the age of the plasma donor. Coagulation was initiated in defibrinated, diluted plasma by contact activation and thrombin activity measured using the chromogenic substrate, S2238. The rate of thrombin generation was assessed by measuring the time taken to reach 50% maximal activity (T50/s). There was a highly significant negative correlation between T50 and age, T50 declining from 93 s at 19 years to 71 s at 65 years (r = -0.637, p less than 0.0001). A strong negative correlation was demonstrated between T50 and FVII level (r = -0.415, p = 0.0007) and FVIII:C level (r = -0.465, p = 0.0001). Although FVII concentration correlated with age (r = 0.307, p = 0.014) no relationship was seen between age and FVIII:C. These data suggest that coagulation rates in plasma accelerate with age. PMID- 1641828 TI - Anticoagulant efficacy and immunogenicity of the selective factor Xa inhibitor antistasin following subcutaneous administration in the rhesus monkey. AB - The antithrombotic efficacy and duration of action of a single subcutaneous administration of the selective factor Xa inhibitor recombinant antistasin (rATS) was evaluated in a rhesus monkey model of mild disseminated intravascular coagulation. rATS (1 mg/kg) was shown to be fully effective and comparable to standard heparin (1,000 U/kg) in the suppression of thromboplastin-induced fibrinopeptide A generation for at least 5 h following a single subcutaneous administration. The absorption rate of rATS, as measured by ex vivo activated partial thromboplastin times (aPTT), mirrored that of standard heparin exhibiting peak anticoagulant activity between 1 and 2 h post administration. The anticoagulant effects of a single rATS dose lasted for longer than 30 h maintaining an aPTT value at least 2-fold higher than baseline. Repeated subcutaneous administrations of rATS resulted in the generation of fully neutralizing antibodies. These results suggest that specific factor Xa inhibition may be as effective as standard heparin in the treatment of venous thrombosis. Due to its antigenicity however, rATS is probably not suitable for chronic subcutaneous anticoagulant therapy. PMID- 1641830 TI - Report of Scientific and Standardization Subcommittee on Neonatal Hemostasis Diagnosis and Treatment of Neonatal Thrombosis. PMID- 1641831 TI - Changes in von Willebrand factor antigen levels in venous occlusion. PMID- 1641832 TI - Increased levels of beta 2-glycoprotein I (aca-Cofactor) in patients with lupus anticoagulant. PMID- 1641833 TI - Acquired von Willebrand's disease in myeloproliferative syndrome: spontaneous remission during pregnancy. PMID- 1641834 TI - [Feline haemobartonellosis (feline infectious anemia): current knowledge]. AB - Fifty years after it was first reported in South Africa (1) and thirty-five years after Haemobartonella felis was detected in the USA (2), we still do not know enough about certain aspects of feline haemobartonellosis (feline infectious anaemia). This overview covers these and known aspects, with the aim of bringing these aspects to the attention of people working in the field of feline medicine. PMID- 1641835 TI - [Felinfo glossarium. Mad cow disease in the cat]. PMID- 1641836 TI - [Mycotic mastitis in cattle]. AB - The literature on aetiology, diagnosis, symptoms, therapy and prognosis of mycotic mastitis in cows is reviewed. The importance of identification of the causative agent for the prognosis is discussed. Some cases of (candida) mastitis recover spontaneously: however, spontaneous recovery or recovery after therapy for mastitis caused by Cryptococcus or Prototheca is rare. Frequent milking of infected teats is important during treatment of mycotic mastitis. If supportive pharmacotherapy is desired, antimycotic drugs could be appropriate, however there is no clear evidence of the effectiveness of this therapy. PMID- 1641837 TI - [Revolutionary discovery]. PMID- 1641838 TI - [Veterinary guidelines for preparation for export of breeding and commercial cattle. Government Department for Inspection of Cattle and Meat 1992]. PMID- 1641839 TI - [What went wrong with the magnesium provision?]. PMID- 1641840 TI - [Veterinarian on the way to a unified Europe]. PMID- 1641841 TI - [Stress in newborn infants: a literature review]. AB - All kinds of handling of sick newborn, especially premature babies, are thought to be stressful events. In order to develop stress reducing programs for those infants, a study was carried out into the reports of stress parameters for newborns in the current literature. B-endorphin answers the best to the needs for a reliable parameter in stress studies. PMID- 1641842 TI - [IgA deficiency: clinical ans immunological evaluation of 28 patients]. AB - Seventeen patients with total IgA deficiency and II with partial IgA deficiency were investigated. Symptoms associated with IgA deficiency were retrospectively studied, and the levels of other immunoglobulins were measured in blood and in saliva. The most important associated complaints were recurrent upper respiratory infections. More than 50% of the symptomatic patients recovered clinically, associated with a recovery of the IgA level or with compensatory humoral immunological mechanisms (such as elevated IgG subclasses or strongly positive secretory IgM). The necessary diagnostic procedures, follow-up of patients and families are described. PMID- 1641844 TI - [Pulmonary artery loop: a cause of life-threatening stridor in the young infant]. AB - Four clinical cases of pulmonary artery sling are reported. As an early recognition of this congenital anomaly can be life-saving for many infants, the most important elements in diagnosis and therapy are described. PMID- 1641843 TI - [Helicobacter pylori infections in children]. AB - In our patient population with chronic aspecific abdominal complaints Helicobacter pylori gastritis is no rarity. This entity has been diagnosed in 10 children out of 48 (mean age: 8 years 11 months) who underwent an endoscopy of the upper gastrointestinal tract. After treatment with amoxicillin and colloidal bismuth subcitrate during a period of 2 weeks the complaints disappeared and an eradication was obtained in 7. Histology of the antral mucosa demonstrated a type B chronic active gastritis in all patients. A Helicobacter pylori specific serology was positive in all 10 patients. This test was also positive in 17 out of 35 asymptomatic first degree family members; this is an illustration for the high family prevalence of Helicobacter pylori. PMID- 1641845 TI - [Symptomatology and treatment of neonatal hypertension]. AB - A newborn child of a diabetic mother is described, who developed neonatal hypertension after birth. Clinical signs were not specific and the diagnosis would have been missed if blood pressure had not been measured. The cause of the neonatal hypertension appeared to be a thrombus in the left renal artery, probably originating from the ductus arteriosus Botalli. Control of the neonatal hypertension according to a stepwise treatment regime was very difficult. Based on our experience and on study of the literature it is advised to start treatment in the acute stage with nifedipine orally or with sodium nitroprusside intravenously. PMID- 1641846 TI - [Lidocaine poisoning in a newborn infant following perineal infiltration for episiotomy]. AB - Intoxication of the newborn by a local anesthetic is a relatively unknown disease. A newborn born alive after being accidentally injected with lidocaine during perineal infiltration for episiotomy is described and the pharmacokinetics and possible therapies are discussed. PMID- 1641847 TI - [A child with Wegener's granulomatosis]. AB - A 13-year old boy is described with painful joints, papular skinlaesions, malaise and haematuria. Impaired renal function and hypertension were found. In the past he frequently suffered of otitis media. Biopsies of kidney and skin lesions showed a vasculitis, furthermore the C-ANCA-titer (anti-neutrophil cytoplasm antibodies) was strongly elevated which justified the diagnosis Wegener's granulomatosis (WG). This disease is seldom seen in childhood. It is a necrotizing vasculitis with granulomas of mostly the respiratory tract and kidneys. Autoantibodies directed against intracellular antigens of neutrophils were first associated with vasculitis in 1982. Since 1988 two ANCA-subtypes have been recognized: C-ANCA and P-ANCA. The C-ANCA appear to be highly specific for diagnosis and follow-up of WG, and to differentiate of other forms of vasculitis (with P-ANCA). If children present with frequent and serious upper respiratory tract infections, with suspicion of a systemic disease it is important to perform the ANCA-test to differentiate between WG and other forms of vasculitis. The patient was treated with prednisone and cyclophosphamide, after which the symptoms and the ANCA-titer decreased. PMID- 1641848 TI - A novel cytotoxicity screening assay using a multiwell fluorescence scanner. AB - A new assay using a multiwell fluorescence scanner was developed for screening cytotoxicity to cells cultured in 96-well microtiter plates. The assay is based on binding of propidium iodide to nuclei of cells whose plasma membranes have become permeable due to cell death. Fluorescence of propidium iodide measured with a multiwell fluorescence scanner increased in proportion to the number of permeabilized cells. After ATP depletion of hepatocytes and neonatal cardiac myocytes with metabolic inhibitors ("chemical hypoxia"), and exposure of Madine Darby canine kidney cells to the toxic chemical, HgCl2, propidium iodide fluorescence progressively increased. Increases of fluorescence were linearly proportional with release of lactate dehydrogenase into the culture medium. Employing this cytotoxicity screening assay, protection by various agents against lethal injury was evaluated in cultured hepatocytes during chemical hypoxia. Inhibitors of cysteine proteases (i.e., antipain, leupeptin, E-64), serine proteases (i.e., PMSF), and aspartic acid proteases (i.e., pepstatin A) did not protect against chemical hypoxia. In contrast, 1,10-phenanthroline, an inhibitor of metalloprotease, markedly protected against the onset of cell death during chemical hypoxia. Half-maximal protection after 60 min occurred at 0.5 microM. Phospholipase inhibitors, chlorpromazine (50 microM) and mepacrine (50 microM), also substantially retarded cell killing. U74006F, an inhibitor of lipid peroxidation, slowed cell killing to a lesser extent during chemical hypoxia and after oxidative stress with t-butyl hydroperoxide. Calciphor, a dimer of prostaglandin B1, did not protect against cell killing during chemical hypoxia or t-butyl hydroperoxide toxicity. In conclusion, this high capacity cytotoxicity assay for cells cultured in 96-well microtiter plates is suitable for rapid screening of potential cytoprotective agents in a variety of cell types. PMID- 1641849 TI - Oxidative DNA damage levels in rats fed low-fat, high-fat, or calorie-restricted diets. AB - Increased fat and caloric content of the diet has been associated with increased mammary tumor incidence. The dietary modulation of cellular redox state may be one mechanism behind this association. We have examined the effects of changes in dietary fat and caloric intake on the levels of 5-hydroxymethyluracil in DNA from rat liver and mammary gland. Female Fischer 344 rats, 40 days old, were maintained on 3% (low-fat), 5% (control), or 20% (high-fat) corn oil diets for 2 weeks. A fourth group of rats had the same daily fat intake as the control group, but total caloric intake was restricted by 40%. As a measure of oxidative DNA damage, 5-hydroxymethyluracil levels were measured in the DNA extracted from liver and mammary gland by gas chromatography-mass spectrometry. 5 Hydroxymethyluracil levels in the liver DNA of the low-fat, high-fat, and calorie restricted groups were decreased relative to that of control, but the only significant decrease was in the calorie-restricted group (p less than 0.01). In the mammary gland DNA, statistically significant decreases in damage were found in each group relative to control (p less than 0.05). The relationship between fat in the diet and oxidative stress is thus complex. These results show that changes in dietary intake of both fat and calories can modulate oxidative DNA damage levels, and the effect of diet was more clearly evident in the DNA from mammary gland than in DNA from liver. PMID- 1641850 TI - Lung mitochondrial function following oxygen exposure and diethyl maleate-induced depletion of glutathione. AB - Diethyl maleate (DEM) pretreatment has previously been shown to result in a transient depletion of lung glutathione and an associated decrease of the time to the onset of rat mortality resulting from exposures to 100% oxygen in vivo. The effects of oxygen exposure on mitochondrial energy metabolism were assessed by measurements of ADP-stimulated rates of O2 utilization by lung homogenates prepared from untreated and DEM-treated rats following 4 and 24 hr of exposure to either air or 100% oxygen. Twenty-four hours of oxygen exposure of untreated rats resulted in significant decreases in lung homogenate ADP-stimulated rates of respiration supported by the substrates, pyruvate, isocitrate, and alpha ketoglutarate. No changes were observed in succinate-supported respiration, indicating that oxygen exposure appears to adversely affect NAD-linked rather than FAD-linked pathways of mitochondrial energy metabolism. The decreased lung mitochondrial glutathione, observed 4 hr following DEM treatment, returned to normal levels following 24 hr of air and oxygen exposure. No effects of glutathione depletion were observed on ADP-stimulated rates of respiratory activity 4 hr following DEM treatment. The DEM-induced transient depletion of glutathione also did not result in any additional detrimental effects on mitochondrial respiratory activity following 24 hr of oxygen exposure in vivo. These results suggested that transient mitochondrial depletion of glutathione does not accelerate the oxygen-induced impairment of mitochondrial energy metabolism. The onset of mortality associated with DEM-pretreatment might therefore result from a failure of glutathione-dependent cytosolic protective mechanisms, rather than from an increased rate of oxygen-induced mitochondrial damage. PMID- 1641851 TI - Detection of a reactive pyrrole in the hepatic metabolism of the pyrrolizidine alkaloid, monocrotaline. AB - Pyrrolizidine alkaloids such as monocrotaline are bioactivated in the liver, resulting in veno-occlusive disease of the liver, pulmonary arterial hypertension, and right ventricular hypertrophy. We have searched for the formation of a reactive, alkylating pyrrole intermediate in the metabolism of monocrotaline by isolated rat liver microsomes, using the sulfhydryl-containing resin, thiopropyl sepharose 6B, as a trapping agent. Control experiments show that a toxic, chemically reactive, alkylating pyrrole such as dehydromonocrotaline binds covalently to the resin via a thioether bond, but that a less toxic, poorly alkylating pyrrole, such as dehydroretronecine, does not. Isolated hepatic microsomes metabolize monocrotaline to produce a pyrrole that binds to the resin, and that can be detected by means of the Ehrlich color reagent (p-dimethylaminobenzaldehyde). The pyrrole is releasable by silver nitrate treatment, thereby establishing it to be bound via a thioether linkage. In buffered ethanolic silver nitrate the major product is 7-ethoxy-1 hydroxymethyl-6,7-dihydro-5H-pyrrolizine (O7-ethyldehydroretronecine). This establishes that the thioether linkage is at the 7-position. The same product is obtained on release of the resin-bound pyrrole formed from the reaction of dehydromonocrotaline with the resin, thereby establishing the intermediacy of dehydromonocrotaline in the metabolism of monocrotaline. PMID- 1641852 TI - Altered intrarenal accumulation of mercury in uninephrectomized rats treated with methylmercury chloride. AB - We tested the hypothesis that the intrarenal accumulation of mercury in rats treated with methylmercury is altered significantly as a result of unilateral nephrectomy and compensatory renal growth. Renal accumulation of mercury was evaluated by radioisotopic techniques in both uninephrectomized (NPX) and sham operated (SO) rats 1, 2, and 7 days after the animals received a nonnephrotoxic intravenous dose of methylmercury chloride (5 mg/kg Hg). At all times studied after the injection of the dose of methylmercury, the renal accumulation of mercury (on a per gram kidney basis) was significantly greater in the NPX rats than that in the SO rats. The increased accumulation was due to a specific increase in the accumulation of mercury in the outer stripe of the outer medulla. Renal cortical accumulation of mercury was similar in both the NPX and SO rats. The percentage of the administered dose of mercury that was present in the total renal mass of the NPX and SO rats ranged between 5 and 15, depending on the day that the renal accumulation was studied. Approximately 40-50% of the total renal burden of mercury in both the NPX and SO rats was in the inorganic form. However, only less than 1% of the mercury in blood was in the inorganic form at the three times accumulation was studied. Very little mercury was excreted in the urine by either the NPX or SO rats. Only about 2 to 3% of the administered dose of mercury was excreted in the urine in 7 days. By contrast, the cumulative fecal excretion of mercury over 7 days was substantial in the NPX and SO rats, and significantly more mercury was excreted in the feces by the NPX rats (about 19% of the dose) than by that in the SO rats (about 16% of the dose). In conclusion, our findings indicate that unilateral nephrectomy and compensatory renal growth cause a significant increase in the accumulation of mercury in the renal outer stripe of the outer medulla in rats exposed to methylmercury. In addition, the findings indicate that the fecal excretion of mercury is also significantly increased. PMID- 1641853 TI - Effect of pregnenolone-16 alpha-carbonitrile and dexamethasone on acetaminophen induced hepatotoxicity in mice. AB - Recently, we demonstrated that a microsomal enzyme inducer with a steroidal structure, pregnenolone-16 alpha-carbonitrile (PCN), markedly decreased the hepatotoxicity of acetaminophen (AA) in hamsters. Therefore, it was of interest to determine if PCN, as well as another steroid microsomal enzyme inducer, dexamethasone (DEX), would decrease the toxicity of AA in mice, another species sensitive to AA hepatotoxicity. Mice were pretreated with PCN or DEX (100 and 75 mg/kg, ip, for 4 days, respectively) and were given AA (300-500 mg/kg, ip). Twenty-four hours after AA administration, liver injury was assessed by measuring serum activities of sorbitol dehydrogenase and alanine aminotransferase and by histopathological examination. Neither PCN nor DEX protected markedly against AA hepatotoxicity in mice; PCN tended to decrease AA-induced hepatotoxicity, whereas DEX was found to enhance AA-induced hepatotoxicity and it produced some hepatotoxicity itself. DEX decreased the glutathione concentration (36%) in liver and increased the biliary excretion of AA-GSH, which reflects the activation of AA, whereas PCN produced neither effect. Thus, whereas PCN has been shown to markedly decrease the hepatotoxicity of AA in hamsters, apparently by decreasing the isoform of P450 responsible for activating AA to N-acetyl-p benzoquinoneimine, this does not occur in mice after induction with either PCN or DEX. In contrast, DEX enhances AA hepatotoxicity apparently by decreasing liver GSH levels and increasing the activation of AA to a cytotoxic metabolite. PMID- 1641854 TI - Blood pressure changes and sympathetic function in rats given cyclohexylamine by intravenous infusion. AB - Intravenous infusion of cyclohexylamine (30-120 mg/kg) caused a dose-dependent increase in blood pressure in urethane-anesthetized rats. The increase in blood pressure was inversely related to the duration of the infusion. The blood pressure returned to baseline values (+/- 5 mm Hg) within 60 min of the end of the infusion after doses of 30 and 60 mg/kg were administered over 20 and 40 min. The plasma concentrations of cyclohexylamine were related linearly to the administered dose and decreased only 27% between the end of the infusion and 60 min later. The concentration-effect relationship showed clockwise hysteresis, indicative of tachyphylaxis, as has been reported in humans (Eichelbaum et al., 1974). Administration of bolus doses of tyramine at the end of the infusion or 60 min later demonstrated the presence of an indirect sympathomimetic response, although this was attenuated to a greater extent by high doses and more rapid infusions of cyclohexylamine. An almost complete loss of response to tyramine was found only in animals given 120 mg/kg over 40 min. The presence of a tyramine response 60 min after the infusion of 60 mg/kg occurred when there was an essentially complete reversal of the hypertensive effect of cyclohexylamine. These data indicate that the hypertensive effect of the indirectly acting sympathomimetic amine cyclohexylamine occurs primarily during rapid increases in plasma concentrations. Tachyphylaxis develops rapidly after the cessation of the infusion which is probably due largely to reuptake of released noradrenaline at low doses and depletion of releasable noradrenaline at high doses. PMID- 1641855 TI - Percutaneous absorption and metabolism of pyrene, benzo[a]pyrene, and di(2 ethylhexyl) phthalate: comparison of in vitro and in vivo results in the hairless guinea pig. AB - The in vitro and in vivo absorption and metabolism of pyrene, benzo[a]pyrene, and di(2-ethylhexyl) phthalate (DEHP) were investigated in the hairless guinea pig. The in vitro method, which involved the use of flow-through diffusion cells and Hepes-buffered Hanks' balanced salt solution containing 4% bovine serum albumin as perfusate, was demonstrated to be a suitable system for predicting in vivo absorption of the above lipophilic compounds. The successful application of the in vitro technique for these compounds is significant because no satisfactory in vitro method has hitherto been developed to predict in vivo absorption of highly lipophilic chemicals. Quantification of parent compounds and metabolites that permeated into perfusates and those that remained in skin discs provided insight into the process by which the chemicals penetrated through the skin. Pyrene was absorbed primarily by a passive diffusion process, although a small fraction of the administered dose was biotransformed into metabolites in the skin and partitioned into the receptor fluid. Absorption of benzo[a]pyrene was mediated by biotransformation processes. A metabolite derived from the ultimate carcinogen of this compound, benzo[a]pyrene r-7, t-8,9,10-tetrahydrotetrol, was identified in the receptor fluid. Most of the administered DEHP remained in the skin and only a very small fraction of the dose partitioned into the receptor fluid in either viable or nonviable skin. Data from the present study led to the conclusion that the in vitro method can be utilized to predict in vivo absorption for compounds of high lipophilicity and that dermal metabolism facilitates partitioning of metabolites into the receptor fluid and hence may affect the biological activities of dermally applied compounds. PMID- 1641856 TI - Exposure to bleached kraft pulp mill effluent disrupts the pituitary-gonadal axis of white sucker at multiple sites. AB - Our recent studies have demonstrated reproductive problems in white sucker (Catostomus commersoni) exposed to bleached kraft pulp mill effluent (BKME) at Jackfish Bay on Lake Superior. These fish exhibit delayed sexual maturity, reduced gonadal size, reduced secondary sexual characteristics, and circulating steroid levels depressed relative to those of reference populations. The present studies were designed to evaluate sites in the pituitary-gonadal axis of prespawning white sucker affected by BKME exposure. At the time of entry to the spawning stream, plasma levels of immunoreactive gonadotropin (GtH)-II (LH-type GtH) in male and female white sucker were 30- and 50-fold lower, respectively, than the levels in fish from a reference site. A single intraperitoneal injection of D-Arg6, Pro9N-Et sGnRH (sGnRH-A, 0.1 mg/kg) increased plasma GtH levels in male and female fish at both sites, although the magnitude of the response was greatly reduced in BKME-exposed fish. Fish at the BKME site did not ovulate in response to sGnRH-A, while 10 of 10 fish from the reference site ovulated within 6 hr. Plasma 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P) levels were depressed in BKME-exposed fish and unlike fish at the reference site, failed to increase in response to sGnRH-A. Testosterone levels in both sexes and 11 ketostestosterone levels in males were elevated in fish from the reference site but were not further increased by GnRH treatment. In contrast, BKME-exposed fish exhibit a transitory increase in testosterone levels in response to the GnRH analog. In vitro incubations of ovarian follicles obtained from fish at the BKME site revealed depressed basal secretion of testosterone and 17,20 beta-P and reduced responsiveness to the GtH analog human chorionic gonadotropin and to forskolin, a direct activator of adenylate cyclase. By comparison, ovarian follicles from fish collected at BKME and reference sites produced similar levels of prostaglandin E basally and in response to a phorbol ester and calcium ionophore A23187, suggesting that BKME effects on ovarian function are selective and do not reflect a general impairment of ovarian function. BKME-exposed fish had plasma levels of testosterone glucuronide proportionately lower than those of reference fish, suggesting that there are site differences in the peripheral metabolism of steroids. These studies demonstrate that BKME exposure affects reproduction by acting at multiple sites in the pituitary-gonadal axis. PMID- 1641857 TI - Galactosamine hepatotoxicity: effect of galactosamine on glutathione resynthesis in rat primary hepatocyte cultures. AB - The effect of galactosamine on the resynthesis of glutathione in rat primary hepatocyte cultures was investigated. Cultured rat hepatocytes were treated with galactosamine (4 mM) 1.5 hr prior to concurrent with, or 1.5 hr after cell attachment; total cellular glutathione was then measured over time. Addition of galactosamine at any of these times suppressed methionine-enhanced glutathione resynthesis in the cultures after a lag period of about 120 min. The lag period was not due to slow uptake of galactosamine by the cultured cells, since cellular UTP levels fell to less than 10% of controls within 60 min, a time frame comparable to that observed in vivo. Neither was the lag period a result of interference with cellular uptake of methionine or with conversion of methionine to cysteine, since the phenomenon was observed regardless of whether methionine or cysteine was used to promote glutathione resynthesis. Addition of uridine, which protects against galactosamine hepatotoxicity in vivo by replenishing hepatic UTP levels, did not prevent the suppression of glutathione resynthesis. The data indicate that (a) galactosamine inhibits the time-dependent resynthesis of glutathione in primary hepatocyte cultures, (b) a lag period exists for this response, and (c) this effect is not directly related to depletion of cellular UTP stores. PMID- 1641858 TI - Epithelial injury and interstitial fibrosis in the proximal alveolar regions of rats chronically exposed to a simulated pattern of urban ambient ozone. AB - Electron microscopic morphometry was used to study the development of lung injury during and after chronic (78 weeks) exposure to a pattern of ozone (O3) designed to simulate high urban ambient concentrations that occur in some environments. The daily exposure regimen consisted of a 13-hr background of 0.06 ppm, an exposure peak that rose from 0.06 to 0.25 ppm, and returned to the background level over a 9-hr period, and 2-hr downtime for maintenance. Rats were exposed for 1, 3, 13, and 78 weeks. Additional groups of rats exposed for 13 or 78 weeks were allowed to recover in filtered clean air for 6 or 17 weeks, respectively. Rats exposed to filtered air for the same lengths of time were used as controls. Samples from proximal alveolar regions and terminal bronchioles were obtained by microdissection. Analysis of the proximal alveolar region revealed a biphasic response. Acute tissue reactions after 1 week of exposure included epithelial inflammation, interstitial edema, interstitial cell hypertrophy, and influx of macrophages. These responses subsided after 3 weeks of exposure. Progressive epithelial and interstitial tissue responses developed with prolonged exposure and included epithelial hyperplasia, fibroblast proliferation, and interstitial matrix accumulation. The epithelial responses involved both type I and type II epithelial cells. Alveolar type I cells increased in number, became thicker, and covered a smaller average surface area. These changes persisted throughout the entire exposure and did not change during the recovery period, indicating the sensitivity of these cells to injury. The main response of type II epithelial cells was cell proliferation. The accumulation of interstitial matrix after chronic exposure consisted of deposition of both increased amounts of basement membrane and collagen fibers. Interstitial matrix accumulation underwent partial recovery during follow-up periods in air; however, the thickening of the basement membrane did not resolve. Analysis of terminal bronchioles showed that short-term exposure to O3 caused a loss of ciliated cells and differentiation of preciliated and Clara cells. The bronchiolar cell population stabilized on continued exposure; however, chronic exposure resulted in structural changes, suggesting injury to both ciliated and Clara cells. We conclude that chronic exposure to low levels of O3 causes epithelial inflammation and interstitial fibrosis in the proximal alveolar region and bronchiolar epithelial cell injury. PMID- 1641859 TI - Rat liver microsomal UDP-glucuronosyltransferase activity toward thyroxine: characterization, induction, and form specificity. AB - Glucuronidation of thyroxine (T4) by liver microsomal UDP-glucuronosyltransferase (UDP-GT) is a predominant pathway by which T4 is deactivated. This study was conducted to characterize in vitro T4 UDP-GT activity in rat liver microsomal preparations, to determine if T4 glucuronidation is mediated by a particular form of UDP-GT, and to determine if T4 glucuronidation can be increased by microsomal enzyme inducers. Characterization of microsomal T4 UDP-GT activity led to the establishment of optimal assay conditions. UDP-GT activity toward T4 was determined in hepatic microsomal preparations from Wistar and Gunn rats, a mutant strain of Wistar rats deficient in several forms of UDP-GT. Hepatic microsomal preparations from Gunn rats glucuronidated T4 at one-third the rate catalyzed by microsomal preparations from Wistar rats. To determine the effect of four inducers that each increase a separate class of UDP-GT, phenobarbital (PB), 3 methylcholanthrene (3MC), pregnenolone-16 alpha-carbonitrile (PCN), clofibrate (CLO), saline, or corn oil was administered to male Sprague-Dawley rats ip for 4 days. T4 UDP-GT activity was increased by PB, 3MC, PCN, and CLO 88, 150, 100, and 160%, respectively on a per-milligram-microsomal-protein basis and 138, 125, 100, and 145% on a per-kilogram-body-weight basis, respectively. Therefore, all four classes of UDP-GT inducers increase T4 glucuronidation, suggesting that T4 is not a selective substrate for a particular form of UDP-GT. PMID- 1641860 TI - Metabolism and lipoperoxidative activity of trichloroacetate and dichloroacetate in rats and mice. AB - Trichloroacetate (TCA) and dichloroacetate (DCA) have been shown to be hepatocarcinogenic in mice when administered in drinking water. However, DCA produces pathological effects in the liver that are much more severe than those observed following TCA treatment in both rats and mice. To identify potential mechanisms involved in the liver pathology, the biotransformation of TCA and DCA was investigated in male Fischer 344 rats and B6C3F1 mice. Rodents were administered 5, 20, or 100 mg/kg [14C]TCA or [14C]DCA as a single oral dose in water. Elimination was examined by counting radioactivity in urine, feces, exhaled air, and carcass. Blood concentration over time curves were constructed for both TCA and DCA at the 20 and 100 mg/kg doses. Analysis of the data reveals two significant differences in the systemic clearance of TCA relative to DCA. First, DCA was much more extensively metabolized than TCA. More than 50% of any single dose of TCA was excreted unchanged in the urine of both rats and mice. In contrast, less than 2% of any dose of DCA was recovered in the urine as the parent compound. Second, while the blood concentration over time curves for TCA were similar in rats and mice, the blood concentrations of DCA were markedly greater in rats compared to those in mice, both when DCA was administered and when DCA resulted from metabolism of TCA. DCA was detected in the urine of TCA treated animals and chloroacetate was found in the urine of DCA-treated animals. These metabolic products would be expected to arise from a free radical generating, reductive dechlorination pathway. To evaluate the ability of acute doses of TCA and DCA to elicit a lipoperoxidative response, additional groups of mice were administered 0, 100, 300, 1000, and 2000 mg/kg TCA or DCA and thiobarbituric acid-reactive substances (TBARS) measured in liver homogenates. Both TCA and DCA enhanced the formation of TBARS in a dose-dependent manner, thereby providing further evidence of a reductive metabolic pathway. DCA was found to be the more potent of the chlorinated acetates in increasing TBARS formation in the livers of both rats and mice. In view of these data, it appears that the more extensive metabolism and rapid rate of elimination of DCA relative to TCA and the more potent lipoperoxidative activity of DCA may be important factors in the pathological effects associated with DCA treatment. PMID- 1641861 TI - Species differences in the metabolism of trichloroethylene to the carcinogenic metabolites trichloroacetate and dichloroacetate. AB - Differing rates and extent of trichloroethylene (TCE) metabolism have been implicated as being responsible for varying sensitivities of mice and rats to the hepatocarcinogenic effects of TCE. Recent data indicate that the induction of hepatic tumors in mice may be attributed to the metabolites trichloroacetate (TCA) and/or dichloroacetate (DCA). The present study was directed at determining whether mice and rats varied in (1) the peak blood concentrations, (2) the area under the blood concentration over time curves (AUC) for TCE and metabolites in blood, and (3) the net excretion of TCE to these metabolites in urine in the dose range used in the cancer bioassays of TCE, and to contrast the kinetic parameters observed for TCE-derived TCA and DCA with those obtained following direct administration of TCA and DCA. Blood and urine samples were collected over 72 hr from rats and mice after a single oral dose of TCE of 1.5 to 23 mmol/kg. The AUC values from the blood concentration with time profiles of TCE, TCA, and trichloroethanol (TCOH) were similar for Sprague-Dawley rats and B6C3F1 mice. Likewise, the percentages of initial TCE dose recovered as the urinary metabolites TCA and TCOH were comparable. Nevertheless, the peak blood concentrations of TCE, TCA, and TCOH observed in mice were much greater than those in rats, while the residence time of TCE and metabolites was prolonged in rats relative to that of mice. DCA was detected in the blood of mice but not in rats. The blood concentrations of DCA observed in mice given a carcinogenic dose of TCE (15 mmol/kg) were of the same magnitude as those observed with carcinogenic doses of DCA. In conclusion, the net metabolism of TCE to TCA and TCOH was similar in rats and mice. The initial rates of metabolism of TCE to TCA, however, were much higher in mice, especially as the TCE dose was increased, leading to greater concentrations of TCA and DCA in mice approximated those produced by carcinogenic doses of the chlorinated acetates makes it highly likely that both compounds play a role in the induction of hepatic tumors in mice by TCE. PMID- 1641862 TI - Propane 2-nitronate is more rapidly denitrified and is more genotoxic than 2 nitropropane in cultured rat hepatoma cells. AB - We have investigated the importance of nitronate formation from 2-nitropropane (2 NP) for the oxidative metabolism and the genotoxicity of 2-NP in 2sFou rat hepatoma cells. Treatment of the cells with 2-NP for up to 3 h resulted in the time-dependent appearance of nitrite in the culture medium and in a weak induction of DNA repair synthesis. Both nitrite formation and repair induction were markedly enhanced in cells exposed to the anionic form of 2-NP, propane 2 nitronate. These observations suggest that propane 2-nitronate, rather than 2-NP itself, is oxidized by the liver cells to yield a DNA-damaging product. The results also indicate that the nitro/nitronate equilibration in intact liver cells is slow, suggesting that nitronate formation represents the rate-limiting step in the metabolic activation of 2-NP. PMID- 1641863 TI - Synergism between aflatoxin B1 and oxytetracycline on fatty acid esterification in isolated rat hepatocytes. AB - The individual and combined effects of aflatoxin B1 (AFB1) and oxytetracycline (OXT) on the synthesis and secretion of triacylglycerols in isolated rat hepatocytes maintained in suspension during 2.5 h were studied. Secretion of triacylglycerols was inhibited by both drugs when administered separately. This inhibition was accompanied by a concomitant elevation of intracellular triacylglycerols only at the highest AFB1 dose tested. Total synthesis of triacylglycerols was not inhibited by AFB1 or by OXT. When the two drugs were simultaneously added to the incubation medium, the AFB1-induced accumulation of intracellular triacylglycerols was no longer observed; the inhibition of secretion was nevertheless identical to that observed with AFB1 alone. Finally, total esterification of palmitate was inhibited by 20% compared to the AFB1 treated cells. These data suggest that OXT inhibits lipid accumulation induced by AFB1 but that this effect is due to an inhibition of total synthesis of triacylglycerols. The mechanism of AFB1's effect and of the interaction between both molecules is discussed. PMID- 1641864 TI - Modulation of hexachlorobenzene-induced hepatic porphyria by methyl isobutyl ketone in the rat. AB - Potential toxic interaction between hexachlorobenzene (HCB) and methyl isobutyl ketone (MiBK) was investigated using two different schedules of toxicant administration. The first schedule involved simultaneous administration of HCB (50 mg/kg/d, p.o. in 10 ml/kg corn oil at 10.00 a.m. for 5 d/wk) and MiBK (7.5 mmol/kg/d, p.o. in 10 ml/kg corn oil at 4.00 p.m. for 3 d/wk) for 6 weeks. The second schedule involved an initial dosing of 25 or 50 mg HCB/kg/d for 12 consecutive days, followed by the administration of 7.5 mmol MiBK/kg every other day for 27 days. When administered simultaneously, MiBK reduced the severity of HCB-induced porphyria, but when given sequentially after HCB accumulation, it enhanced the porphyrinogenic response. These results suggest that the effect of combined exposure to HCB and MiBK on hepatic porphyria depends on the sequence of the administration of both chemicals, and that the mechanism involved in this interaction may invoke both the induction and inhibition of specific hepatic isoenzymes by MiBK. PMID- 1641865 TI - The role of propranolol and atropine in mitigating the toxic effects of scorpion venom on rat electrocardiogram. AB - The effects of the scorpion Leiurus quinquestriatus (H.&E.) venom on electrocardiogram (ECG) parameters such as P-R and Q-T intervals and R and T wave amplitudes were investigated in anesthetized rats. Venom was administered intramuscularly (i.m.) at three doses (100, 200 and 400 micrograms/kg). ECG limb lead II was recorded for 4-h sessions. Because autonomic nervous system tone plays an important role in influencing ECG findings, another study was completed with concomitant pharmacologic autonomic nervous system blockade. Propranolol or atropine was injected 20 min before venom administration in two groups of rats. The results indicated that the venom has drastic effects on the electrical activity of the heart. The Q-T interval developed a dose-response relationship after venom administration. Propranolol abolished the toxic effects of the venom on P-R and Q-T intervals as well as on R wave amplitude, while atropine had no effect on the ECG changes produced by the venom. PMID- 1641866 TI - Toxic neurofilamentous axonopathies and fast anterograde axonal transport. IV. In vitro analysis of transport following acrylamide and 2,5-hexanedione. AB - Recent investigations into the mechanisms of neurotoxicity of acrylamide and gamma-diketones have demonstrated reductions in the delivery of radiolabelled proteins to the distal axon. To differentiate a toxicant-induced compromise in the capacity of the fast anterograde axonal transport system from a neuron cell body processing effect, selective exposure of either the L5 dorsal root ganglion or sciatic nerve to 0.7 mM acrylamide (ACR) or 4 mM 2,5-hexanedione (2,5-HD) was performed during in vitro transport. Nerve exposure to ACR decreased the quantity of transport by 32%, 2,5-HD reduced the quantity by 44%. Ganglion exposure produced no significant changes. We conclude that both toxicants penetrate the nerve barriers and act directly and/or indirectly on the axonal transport mechanisms to cause the reductions in transport. PMID- 1641867 TI - The renal handling of sodium and potassium in environmental cadmium-exposed subjects with renal dysfunction. AB - To clarify using clearance methods the renal handling of sodium and potassium in a population with environmental cadmium (Cd)-induced renal dysfunction, 76 Cd exposed subjects (32 men and 44 women) and 36 non-exposed subjects (18 men and 18 women) were selected. Fractional excretions of potassium and beta 2-microglobulin were higher in the Cd-exposed subjects than in the non-exposed subjects, while the fractional excretion of sodium in the Cd-exposed subjects was equal to that of the non-exposed subjects. The urinary excretion rate of sodium was significantly lower in the Cd-exposed subjects than in the non-exposed subjects, while no significant difference was found in the urinary potassium excretion rate. Fractional excretion of sodium showed a significant correlation with age in all the subjects, while that of potassium significantly correlated with serum beta 2-microglobulin. These results indicate that increases in the fractional excretion of sodium or potassium do not directly signify increased urinary excretion of sodium or potassium in Cd-induced renal tubular dysfunction. The fractional excretion of potassium may be more affected by Cd-induced renal dysfunction, while that of sodium appears to be more related to age. PMID- 1641868 TI - Effect of phenobarbital treatment on carbon tetrachloride-mediated cytochrome P 450 loss and diene conjugate formation. AB - The effect of phenobarbital treatment on the linkage between carbon tetrachloride mediated cytochrome P-450 loss and lipid peroxidation in rat liver microsomes was studied. Male Sprague-Dawley rats, pretreated with 3 daily i.p. doses of phenobarbital (50 mg/kg) or saline, were orally dosed with carbon tetrachloride (0.01-2.5 ml/kg), with liver microsomes prepared at 7.5-180 min after carbon tetrachloride treatment. In vivo cytochrome P-450 loss displayed pseudo-first order kinetics, and the initial rates of diene conjugate formation were saturable with dose. Phenobarbital pretreatment decreased the in vivo t0.5,max from 27.0 to 15.6 min, and increased the Kd,app from 0.78 to 1.30 ml/kg for carbon tetrachloride mediated cytochrome P-450 loss. Phenobarbital had no effect on the in vivo Vmax (1.03 to 1.04 delta OD232 nm/min/mg phospholipid) for carbon tetrachloride mediated diene conjugate formation, but decreased the Km,app from 0.22 to 0.10 ml/kg. These results are consistent with destruction of cytochrome P 450 heme resulting from a metabolite which does not leave the site of generation, and with phenobarbital pretreatment enhancing the initiation of lipid peroxidation. PMID- 1641870 TI - Effect of caloric restriction on hepatic nuclear DNA damage in male Fischer 344 rats treated with aflatoxin B1. AB - Caloric restriction is known to reduce chemically-induced tumor incidence in laboratory animals. The effect is believed to be mediated in part by modification of hepatic drug metabolism, including both phase I and phase II enzymes. Using aflatoxin B1 (AFB1) as a model carcinogen, we studied the effect of caloric restriction on the modification of rat liver nuclear DNA by AFB1 and DNA damage due to the formation of apurinic sites from the AFB1-DNA adduct removal process. Caloric restriction reduced the metabolic activation of AFB1 which resulted in a decrease of AFB1-DNA binding by more than 50%. The results of the study of the effect of caloric restriction on the AFB1-induced DNA strand breakage assayed by the alkaline unwinding technique showed that caloric restriction protected the formation of apurinic sites from the AFB1-DNA adducts and reduced the double strand DNA breakages by 1.3-2.5-fold. Thus, the lower initial AFB1-DNA binding and less DNA damage, presumably by the less apurinic sites formed during the depurination process of AFB1-DNA adducts, contributed to the protective effect of caloric restriction. PMID- 1641869 TI - The effects of aluminum ingestion on intestinal cadmium absorption, lipid peroxidation and alkaline phosphatase activity. AB - Consumption of dietary aluminum (A1, 2000 or 4000 ppm) for 1 month did not influence mouse body weight. In order to estimate an absorption of cadmium (Cd) from the gastrointestinal tract, mice were intubated twice every 24 h with Cd (CdCl2). In the A1-supplemented mice, Cd absorption increased rather than decreased. Intestinal Cd and metallothionein concentrations were increased by the A1 supplement. Intestinal alkaline phosphatase activity and lipoperoxide concentrations were also enhanced by A1 ingestion. Of course, intestinal A1 concentration was at a high level in the A1-supplemented groups. However, A1 accumulation was not observed in the liver. The increase of Cd absorption may be due to an abnormality of the gut wall caused by the A1. Our results suggest that A1 is not inert for animals, even though A1 absorption is poor. PMID- 1641871 TI - Cardiovascular, metabolic and neurologic effects of carbon monoxide and cyanide in the rat. AB - Levine-prepared, female Sprague-Dawley rats were used to investigate the effects of carbon monoxide (CO) and cyanide (CN) on heart rate, blood pressure, hematocrit, body temperature, blood glucose, lactate, and neurologic function. Rats were exposed to either 2400 ppm CO, 1500 ppm CO, 4 mg/kg NaCN, or both 1500 ppm CO and 4 mg/kg NaCN for 90 min, followed by 4 h of room air recovery. Following exposure to 2400 ppm CO, rats exhibited a significant bradycardia which normalized by 2 h of recovery. All groups exhibited an initial hypotension which was either maintained or exaggerated during exposure in all but the rats exposed to CN, and which returned to pre-exposure values by 90 min. All groups experienced a significant hypothermia during the exposure period, with those in the 1500 ppm CO or the CN returning to initial values over the recovery period. The only significant change in hematocrit was due to 2400 ppm CO (4.1% increase). During exposure, all groups experienced an initial surge in glucose concentration which was maintained in all but rats exposed to 2400 ppm CO. The greatest hyperglycemic response resulted from the combination of CO and CN, whereas 2400 ppm CO produced the smallest. CN alone produced no significant rise in lactate concentration. However, lactate concentration in all other groups was significantly elevated during the exposure period, returning to initial values by 4 h of recovery. Lactate concentrations and neurologic deficit in rats exposed to 1500 ppm CO, when added to those rats treated with CN, closely approximated the lactate and neurologic deficit of the combination treatment. Neurologic deficit was greatest in rats exposed to 2400 ppm CO. While in most cases the responses of the rats to CO and CN differed whether the substances were administered alone or in combination, a synergistic relationship is not suggested. An additive or less than additive relationship is more likely. PMID- 1641872 TI - Do intracellular Ca2+ activity and hepatic glutathione play a role in the pathogenesis of lithocholic acid-induced cholestasis? AB - The possible relevance of alterations in intracellular Ca2+ and hepatic glutathione levels (GSH) in the pathogenesis of cholestasis induced by lithocholic acid (LCA) was examined by comparing effects of LCA and acetaminophen on these parameters and bile flow (BF) in rats. Intracellular Ca2+ activity was measured via glycogen phosphorylase a determination in rats given an intravenous bolus injection of either LCA (12 mumol/100 g body wt.), acetaminophen (60 mg/100 g body wt.), or a mixed solution of LCA and acetaminophen. BF was reduced immediately after LCA administration, with a maximum decrease occurring at 60 min followed by an increase to normal values at 210 min. On the other hand, glycogen phosphorylase a activity was elevated during all time periods after LCA treatment. Hepatic glutathione followed the BF curves being markedly depleted at the peak of cholestasis (60 min) and normal in the total recovery period (210 min). In contrast, acetaminophen had no effect on BF but significantly increased glycogen phosphorylase a activity and depleted hepatic glutathione levels. These results suggest that cholestatic effect of LCA is not due to changes in intracellular Ca2+ or hepatic glutathione levels. PMID- 1641873 TI - Induction of cytochrome P-450 by dimethyl sulfoxide in primary cultures of adult rat hepatocytes. AB - Treatment of hepatocyte cultures with dimethyl sulfoxide (DMSO) induced P-450IIE1 specific aniline 4-hydroxylase activity and P-450IA1-specific ethoxyresorufin O deethylase activity at a concentration of 0.1% (v/v). The P-450IIB-specific pentoxyresorufin O-deethylase activity was induced only at the 2% (v/v) level. Dot blot analysis of the total cellular RNA and cycloheximide treatment of the culture suggested that induction of ethoxyresorufin O-deethylase activity by DMSO may be due to the increase of de novo synthesis of the P-450IA1 protein, not to accumulation of mRNA in the hepatocyte culture. PMID- 1641874 TI - No evidence of intracellular oxidative stress during ischemia-reperfusion damage in rat liver in vivo. AB - The role of the intracellular generation of reactive oxygen species in the pathogenesis of ischemia-reperfusion damage of the liver was investigated in two in vivo rat models. Global hepatic ischemia was produced in the left and median lobes for 90 min followed by 60 min reperfusion to the total organ (model A) or only to the ischemic lobes (model B). Although both regimens caused significant rises in serum transaminases, this rise was higher in model B. In neither model was intracellular hydrogen peroxide production nor increased glutathione disulfide in bile found. The activities of various antioxidant enzymes were not affected by ischemia or ischemia-reperfusion. In conclusion, oxygen-free radicals are unlikely to be produced in the cells of rat liver during ischemia reperfusion. PMID- 1641875 TI - Comparative hepatotoxicity of cholic acid, deoxycholic acid and lithocholic acid in the rat: in vivo and in vitro studies. AB - Until now, the cytotoxicity of the bile acids was mostly seen as being inversely associated with their degree of lipophilicity. The present study aimed at comparing the hepatotoxicity of cholic acid (CA), deoxycholic acid (DCA) and lithocholic acid (LCA), which are respectively, tri-, di- and monohydroxylated bile acids. For in vivo studies, the bile acids have been given at the dose of 0.5% or 1% in the diet of male Wistar rats for 2 weeks. The histological analysis of the liver, and the measurement of serum parameters of cytotoxicity and cholestasis (aminotransferases activity, bilirubin and total bile acids concentration), indicate that, among the bile acids tested, DCA is the most hepatotoxic, at both doses, while CA is the least hepatotoxic and cholestatic compound. Moreover, DCA is the only bile acid which, when given at the dose of 0.5%, induces lipid peroxidation in the liver, as evidenced by the measurement of thiobarbituric reactive substances in liver homogenates. The analysis of bile acids in liver homogenates by gas liquid chromatography revealed that feeding the animals with DCA results in its hepatic accumulation. Feeding rats with LCA or CA only slightly modifies the proportion of tri-, di- and monohydroxylated bile acids in the liver, as compared to controls. An in vitro experiment aimed at studying the hepatocellular lysis induced in vitro by the three bile acids by measuring the release of lactate dehydrogenase in the incubation medium of surviving hepatocytes in suspension. At a concentration of 1 mM, only DCA induces a significant cellular lysis, while at this concentration the lytic effects of CA and LCA are progressive and time-dependent. From this study, we gather that the hepatotoxicity of bile acids does not necessarily depend on their degree of hydroxylation. Our results are in accordance with some studies in rat hepatocarcinogenesis, showing a predominant initiating and promoting effects of DCA, as compared to LCA. PMID- 1641876 TI - Evaluation of the interaction of benzene and toluene on the urinary excretion of t,t-muconic acid in rats. AB - The influence of simultaneous exposure to benzene and toluene on the urine excretion of t,t-muconic acid (t,t-MA) was examined in rats. t,t-MA was measured from 24-h urine of rats subjected to a single 4-h exposure to 5 or 20 ppm benzene and/or 50, 100, 200 or 1000 ppm toluene. Coexposure lowered t,t-MA excretion in a concentration-dependent manner, especially in the 20 ppm benzene group where the decrease averaged 28, 44 and 85% after exposure to 100, 200 and 1000 ppm toluene, respectively, as compared to benzene-exposed groups alone. The data confirm the sensitivity of t,t-MA as an indicator of benzene exposure and point out that measurement of t,t-MA may underestimate the exposure to benzene in the presence of toluene. PMID- 1641878 TI - Clinical manifestations of filariasis in Fujian, China. PMID- 1641877 TI - Primary medical care in Seychelles. AB - This paper describes some of the current health problems faced by a tropical country whose standard of living and lifestyle is approaching that of many countries in Western Europe. Long-term health problems such as cardiovascular diseases and diabetes have become at least as important as infectious diseases. A change in approach to a more proactive style of primary care is needed to allow the contribution of community doctors to be effective. The system of primary care in the Republic of Seychelles is based on the UK model of general practice where recent improvements in education and organization are raising standards. How some of these improvements might be transferred elsewhere is discussed. PMID- 1641879 TI - The bioavailability of a novel taste-masked formulation of quinine. PMID- 1641880 TI - Podoconiosis (endemic non-filarial elephantiasis) in two resettlement schemes in western Ethiopia. AB - In a population-based study of podoconiosis in two resettlement schemes in western Ethiopia, we found that 5% of 194 settlers and 9% of 222 indigenous people were affected. Prevalence rates were generally higher in males than females and increased with age, indicating sex differences in occupationally linked trauma to the feet and the cumulative effect of long-term exposure to volcanic soils. Persons wearing shoes had significantly lower rates than those usually walking barefoot. Suggestions are made for the control of podoconiosis. PMID- 1641881 TI - Antisnakevenom: an over-used medication. AB - Fifty-five cases of snakebite were retrospectively analysed for the indications for the use of anti-snakevenom (ASV). Sixty-seven per cent of patients received treatment with ASV. Of these, 47% had features of systemic envenoming, 30% had features of local envenoming and 22% had no features of envenoming, either systemic or local. When WHO guidelines were strictly applied, it was found that in 44% of cases, ASV was used without adequate indication. PMID- 1641882 TI - The International Federation of Red Cross and Red Crescent Societies. PMID- 1641883 TI - Neoplastic transformation of chronic ulcers in leprosy. PMID- 1641884 TI - Appropriate orthopaedic care in the Third World. PMID- 1641885 TI - Traditional health workers. PMID- 1641886 TI - Could the law governing the use of 'prescription-only' medicines be extended to traditional medicines? PMID- 1641887 TI - Taylor Pressure-Reducer in cataract surgery. PMID- 1641888 TI - Malnutrition and malaria gave him anaemia, then the blood transfusion gave him HIV. PMID- 1641889 TI - New emergency health kit: disasters supplement. PMID- 1641890 TI - Acute suppurative thyroiditis: increased incidence in Zambia. PMID- 1641891 TI - Sutureless circumcision. PMID- 1641892 TI - The problem of under-registration of infant deaths in Jamaica. PMID- 1641893 TI - Dental treatment needs in an African obstetric population. PMID- 1641894 TI - Colostomy: indications, complications and management: the Zaria experience. PMID- 1641895 TI - Clinical characteristics of tuberculous lymphadenitis in Tanzania. PMID- 1641896 TI - An unusual presentation of gastro-oesophageal reflux--Sandifer's syndrome. PMID- 1641897 TI - Tuberculosis of the stomach. PMID- 1641898 TI - Visceral leishmaniasis in a 6-week-old infant: possible congenital transmission. PMID- 1641899 TI - Postoperative tetanus following cryosurgery for haemorrhoids. PMID- 1641900 TI - Mebendazole with levamisole in tropical pulmonary eosinophilia: an alternative in diethylcarbamazine allergy. PMID- 1641901 TI - A simple method for the re-tightening of loose cervical cerclage stitch. PMID- 1641902 TI - Traditional healers. PMID- 1641903 TI - Letter from Denis Burkitt. PMID- 1641904 TI - [The morphological and functional characteristics of human aortic endothelium. II. Cellular polymorphism and the incorporation of 3H-thymidine in a culture]. AB - The content of multinuclear endothelial cells and the ability of cells to incorporate 3H-thymidine were studied in primary cultures isolated from zones of low (LP) and high (HP) probability of atherosclerosis of adult human aortas. It was found that the percentage of multinuclear EC was at mean 2-fold higher in cultures from HP zones compared to LP zones of the same vessels. In primary cultures and in the first passage cultures only small mononuclear EC were able to incorporate 3H-thymidine. A significant decrease in the thymidine index (TI) was found only in cultures from HP zones of atherosclerotic aortas. In cultures of EC from the LP zones of these aortas the TI was as high as in cultures from the LP and HP zones from grossly normal vessels. PMID- 1641905 TI - [The role of satellite DNA in chromatin spatial organization in the interphase nucleus]. AB - Problem of three-dimensional structure of chromatin is reviewed. Data concerning ranged distribution of chromosomes in nucleoplasm are shown. Special attention being paid to the role of nuclear matrix in maintenance of nucleus topology. Possible role of satellite sequences and DNA-binding proteins is discussed. PMID- 1641906 TI - [The programmed cell death of murine BW5147 thymoma under the action of dexamethasone]. AB - By flow cytometry, imitation modelling and biochemical analysis, the mode and kinetics of dexamethasone-treated T-lymphoma cell death were studied. The hormone was shown to induce delays in pre- and postsynthetic phases of the cell cycle and the death of part of cells. A short exposure to dexamethasone reveals its cytostatic rather than cytolytic effect. Following G2/M delay and cytokinesis, part of cells dies. A reduced serum concentration (2%) causes shorter delays in the cell cycle and a more rapid cell death. Dexamethasone stimulates apoptosis which is indicated by internucleosomal DNA fragmentation, and by a coincidence in time of the processes of DNA degradation and increase in the other membrane permeability. These results are discussed in relation to the cell death and proliferation. PMID- 1641907 TI - [The cellular apoptosis of murine BW5147 thymoma during cold shock]. AB - The mode of T-lymphoma cell death induced by cold shock was studied. The rewarming of cells at 37 degrees C following a brief period of cold (0 degrees C) resulted in internucleosomal DNA fragmentation. The cells underwent cold shock mediated apoptosis only at a reduced (2%) serum concentration. The apoptosis was not blocked by macromolecular synthesis inhibitors such as cycloheximide and antinomycin D, or by Quin-2. EGTA per se was responsible for the initiation of cell death. Colchicine also induced internucleosomal fragmentation of DNA. Our findings suggest that cold shock induced apoptosis is associated with low temperature mediated disruption of microtubules. The role of Ca2+ and growth factors in cold shock induced cell death is discussed. PMID- 1641908 TI - [The effect of the UV microirradiation of the centrosome on cell behavior. III. The ultrastructure of the centrosome after irradiation]. AB - One of the spindle poles of mitotic PK cells was irradiated with UV microbeam in metaphase or in anaphase. Electron microscopy showed that immediately after irradiation the microtubules around the centrosome were maintained, and that the ultrastructure of both irradiated and nonirradiated poles was similar. After microirradiation of the centrosome in metaphase, the mitotic halo around this centrosome was retained, but in due time the number of microtubules was getting less compared to that around the nonirradiated centrosome. When daughter cells with irradiated centrosomes are passing into the interphase, their centrioles are not separated from each other, no primary cilia are formed, and no replication of centrioles occurs. In the interphase cells with irradiated centrosomes, satellites are formed on the active centriole, but centrosome-attached microtubules are practically absent. PMID- 1641909 TI - [The radiomodification of ion-transporting membrane enzymes in an experimental CNS syndrome]. AB - A study was made of the radiomodified action of adenylic junction on the rat's brain plasmatic membranes during experimental CNS-syndrome, after a 24 h postirradiation, according to the test of enzyme activity changes of membrane bound enzymes. Among ATP, ADP, AMP and adenosine--only the latter shows a radioprotective effect in later periods of irradiation. PMID- 1641910 TI - [Balanced translocation t(17p--; 23p+) in the chimpanzee]. AB - A chimpanzee family was studied, in which the father had a balanced translocation t(17p--; 23p+). The mother showed the normal female chromosome complement. Their daughter had also the normal female karyotype, but with heteromorphic chromosomes 23. A cytogenetic analysis was made using G- and Q-banding techniques and in addition an alkaline silver method for NOR staining. A mechanism of the translocation inheritance is discussed. PMID- 1641911 TI - [The cytochemical demonstration of glycoproteins and glycolipids in Sarcocystis muris sarcocysts]. AB - An electron cytochemical study of glycoproteins and glycolipids was made for the mature sarcocysts of Sarcocystis muris. Glycoprotein structures as branched fibrilles were seen on the surface of the sarcocyst wall. The fibrillar and granular glycoprotein structures were found in the ground substance of sarcocysts near the cyst wall and in the septae. In the plasmalemma of two types of cyst stages (merozoites and intermediate cells), glycoprotein fibrillar structures were revealed connecting these two cell types with each other. The third type cyst stages, i.e. the metrocytes, are situated separately without any fibrillar connections between them and other cyst stages being observed. This question is discussed in terms of the problem of cytodifferentiation. The fibrillar and granular glycoprotein material is scattered over the cytoplasm of the cyst stages, being especially concentrated in micronemes, rhoptries and around amylopectin granules. The control ultrathin sections were treated with saliva or pronase for the aims of protein identification in the material under study. In addition to glycoprotein, some glycolipids material was detected in the sarcocysts in the form of drops surrounded with thin glycoproteinaceous layers. Glycolipids were found in the ground substance of sarcocysts near the cyst stages and in the parasite cell cytoplasm around the micronemes and rhoptries. The data obtained are discussed in connection with the functional role glycoproteins and glycolipids play in S. muris. PMID- 1641912 TI - Optimization of quantitative electron energy loss spectroscopy in the low loss region: phosphorus L-edge. AB - The purpose of this study was to optimize quantitative electron energy loss spectroscopy (EELS) of elements that have characteristic edges in the low energy loss region and are components of organic matrices. The optimum parameters for phosphorus L2,3-edge (at 135 eV) detection were determined by numerical analysis of computer-generated, Poisson-noisy spectra and by experimental measurements (at 80 keV) of films of the phosphoprotein, phosvitin. When the first, second and third valence electron/plasmon scatterings are included in the multiple least squares (MLS) fit, the background subtraction of (first-difference) spectra is significantly more accurate than that obtained with the "inverse power law" method, even for a specimen thickness of only 0.25 lambda. Taking into account the effects of plural scattering, the optimal thickness for P quantitation is approximately 0.3 lambda. Signal-to-noise (S/N) ratio decreases rapidly with thickness, and at 1.0 lambda, it is only about 60% of the optimum S/N. The combined effects of the statistical uncertainty of measurements and of the systematic error due to gain variations of the parallel detector were evaluated, and the relative sensitivities of the no-difference (raw spectrum), first difference and second-difference methods were compared. For channel-to-channel gain variations greater than 0.1% and up to 0.8%, the first-difference method results in the lowest uncertainty of P measurements. In the absence of gain variations, direct fitting provides the greatest sensitivity (least uncertainty), whereas at larger gain variations it may be necessary to use the second difference method. The optimum energy shift for collecting a first-difference spectrum, approximately 15 eV, did not show any great variation between 5 and 25 eV, and is, in general, specimen dependent. Quantitation with EELS showed excellent correlation with simultaneous electron probe X-ray microanalysis, but, for the detection of P in a 0.25 lambda thick specimen, EELS was approximately five to six times more sensitive than X-ray. The minimal detectable P concentration, with 0.5 nA beam current for 100 s in a 0.25 lambda thick specimen, was 8.4 mmol/kg (0.01 at%) at the 99% confidence level, equivalent to 34 phosphorus atoms for a 15 nm probe. This value is close to the theoretical prediction of 7.5 mmol/kg, and can be improved only by further reducing the gain variation and directly fitting the non-difference spectrum. Appropriate reduction of the gain variations to less than 0.1% would result in a further, approximately two-fold, improvement in the parallel EELS detection system.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1641913 TI - 3D reconstruction from the Fourier transform of a single superlattice image of an oblique section. AB - An image of a thin oblique section through a 3D crystal exhibits superlattice periods much larger than the unit cell dimensions of the crystal. Within a superlattice period the contents of the unit cell of the 3D crystal are sampled at different levels, so that a 2D image of the section contains 3D information about the crystal. The 2D Fourier transform of an electron micrograph of such an oblique section thus exhibits superlattice spots, which provide an estimate of the 3D transform of the original crystal. The strengths of the observed spots are reduced from their true values by convolution with a weighting function that depends on section thickness. A method is described that uses phase relationships among symmetry-related structure factors to determine the section thickness and hence the weighting function. Wiener filter deconvolution of the section thickness is performed, in which the filter level is set by the ratio of diffraction spot intensity to background intensity. From the deconvoluted set of structure factors a 3D map of the unit cell can be computed by a standard crystallographic Fourier program. The approach is illustrated with images of oblique sections through rigor insect flight muscle. PMID- 1641914 TI - Fibrocartilaginous emboli. AB - Fibrocartilaginous embolism (FCE) is an acute ischemic myelopathy, primarily of large or giant breed dogs, which results from occlusion of blood vessels within the spinal cord parenchyma or the adjacent leptomeninges by masses of fibrocartilage. Lateralizing and asymmetric neurologic deficits are very suggestive of spinal cord infarction. The diagnosis of FCE is made by eliminating causes of acute compressive myelopathy such as trauma and intervertebral disc herniation. Patients with lower motor neuron deficits secondary to FCE have a more guarded prognosis than those with upper motor neuron deficits. In most instances, if recovery is to occur, improvement will be evident within the first 10 days after the onset of clinical signs. PMID- 1641916 TI - Diseases of the spine. PMID- 1641915 TI - Discospondylitis. AB - The etiopathogenesis and diagnosis of discospondylitis are reviewed. Various therapy options are described. Also included is a discussion of the appropriate usage of specific antimicrobial agents. PMID- 1641917 TI - Approach to the patient with spinal disease. AB - The approach to the patient suspected of having spinal disease should be methodical to assure an accurate diagnosis that is cost-effective with minimal risk to the patient. Using a problem-oriented approach will facilitate attaining this goal. A neurologic examination should enable the veterinarian to localize to one of four spinal cord segments or the cauda equina. PMID- 1641918 TI - Cerebrospinal fluid analysis. AB - Accurate interpretation of cerebrospinal fluid (CSF) changes can only be made in the context of the differential diagnosis for each case. The routine analysis of CSF cell number and type as well as CSF total protein can provide information that suggests a specific mechanism or disease, but is often inconclusive. Further information obtained from CSF protein electrophoresis and immunoglobulin determination and calculation of an albumin quota and IgG index can lend additional support for the suspected mechanism of disease. Paired serum and CSF antibody titers for specific organisms can be useful to confirm the presence of a systemic or nervous system infection. Current research on detecting antibodies against nervous tissue components in CSF should result in better diagnostic capabilities and understanding of the pathophysiology of certain disorders in the future. PMID- 1641919 TI - Radiography, myelography, computed tomography, and magnetic resonance imaging of the spine. AB - Various methods of documenting pathologic change in the spine and spinal cord are available to the veterinary practitioner. Intimidation caused by the imaging modality and the fear that one will not be able to recognize or diagnose a lesion are the factors that limit the use of diagnostic imaging. One needs only to be able to recognize the variations of normal anatomy to be successful. Once an abnormal area has been identified, the diagnosis is soon to follow. Therefore one should concentrate on improving the simple skills associated with image interpretation and normal anatomy. Lesion identification and definitive diagnoses will follow by natural progression. PMID- 1641920 TI - Electrodiagnostic examination. Somatosensory evoked potentials and electromyography. AB - The anatomic/physiologic basis and uses of somatosensory evoked potential recordings are presented. A brief summary of the use of electromyography in spinal cord diseases is included. PMID- 1641921 TI - Spinal trauma. Pathophysiology and management of traumatic spinal injuries. AB - Spinal trauma can originate from internal or external sources. Injuries to the spinal cord can be classified as either concussive or compressive and concussive. The pathophysiologic events surrounding spinal cord injury include the primary injury (compression, concussion) and numerous secondary injury mechanisms (vascular, biochemical, electrolyte), which are mediated by excessive oxygen free radicles, neurotransmitter and electrolyte alterations in cell membrane permeability, excitotoxic amino acids, and various other biochemical factors that collectively result in reduced SCBF, ischemia, and eventual necrosis of the gray and white matter. Management of acute spinal cord injuries includes the use of a high-dose corticosteroid regimen within the initial 8 hours after trauma. Sodium prednisolone and methylprednisolone, at recommended doses, act as oxygen radical scavengers and are anti-inflammatory. Additional considerations are the stability of the vertebral column, other conditions associated with trauma (i.e., pneumothorax), and the presence or absence of spinal cord compression, which may warrant surgical therapy. Vertebral fractures or luxations can occur in any area of the spine but most commonly occur at the junction of mobile and immobile segments. Dorsal and dorsolateral surgical approaches are applicable to the lumbosacral and thoracolumbar spine and dorsal and ventral approaches to the cervical spine. Indications for surgical intervention include spinal cord compression and vertebral instability. Instability can be determined from the type of fracture, how many of the three compartments of the vertebrae are disrupted, and on occasion, by carefully positioned stress studies of fluoroscopy. Decompression (dorsal laminectomy, hemilaminectomy, or ventral cervical slot) is employed when compression of the spinal cord exists. The hemilaminectomy (unilateral or bilateral) causes less instability than dorsal laminectomy and therefore should be used when practical. The preferred approach for atlantoaxial subluxation is ventral, and the cross pinning, vertebral fusion technique is used for stabilization. Fracture luxations of C-2 are repaired with small plates on the ventral vertebral body. The thoracic and upper lumbar spine is stabilized with dorsal fixation techniques or combined dorsal spinal plate/vertebral body plate fixation. Several methods of fixation can be used with lower lumbar or lumbosacral fractures, including the modified segmental technique and the combined dorsal spinal plate/Kirschner-Ehmer technique. PMID- 1641922 TI - Intervertebral disc disease. AB - This article describes the functional anatomy of intervertebral discs and their relationship to the vertebrae and spinal cord. The pathologic events and clinical complications of intervertebral disc disease are described. A discussion of proper staging of disc disease and appropriate conservative management of degenerative disc disease is included. PMID- 1641923 TI - Surgical treatments for intervertebral disc disease. AB - Surgical treatments for intervertebral disc disease are useful for animals with gradually progressive, severely acute, or recurrent lesions. Surgical patients require a diligent neuroradiographic evaluation to confirm location and severity of the discopathy and rule out conditions unrelated to disc disease. Although controversial, some surgeons advocate fenestration for recurrent pain or mild ataxia associated with a noncompressive lesion. Decompressive procedures are recommended for treatment and prognostication of compressive disc-associated myelopathy. Foraminotomy is reserved for patients with lateralizing extrusions confirmed with myelography or newer imaging modalities (CT, MRI). Future treatments for animals may include chemonucleolysis or various discectomy procedures currently performed in humans with symptomatic disc disease. PMID- 1641924 TI - Decompressive procedures. Indications and techniques. AB - Hemilaminectomy and dorsal laminectomy are the surgical techniques most suited for decompression of the thoracic, thoracolumbar, lumbar, and lumbosacral spine. Hemilaminectomy is preferred for decompressing the spinal cord before applying fixation devices for fractures/luxations. Dorsal laminectomy is the method of choice for exploration of the spinal canal and for decompression of the lumbosacral region. Either method is applicable to removal of herniated intervertebral disc material and fenestration of other disc spaces. PMID- 1641925 TI - Cervical vertebral malformation/malarticulation syndrome in large dogs. AB - To anticipate improvement of a chronically affected animal may be expecting too much because reserve or functional spinal cord tissue may be minimal. An accurate prognosis is sometimes impossible to formulate because the extent of spinal cord damage is not known. Treatment may result only in halting progression of the disease, and even with total relief of spinal cord compression, recovery may be minimal. Animals with minimal neurologic deficits treated early in the course of the disease with adequate decompression and stabilization are more likely to return to function. The goals of treatment for cervical spinal cord compression are decompression and stabilization of the affected area. Adequate stabilization may result in atrophy of the soft tissues and further decompression once stabilization is achieved (see Fig. 3). If stabilization is not provided, adequate decompression of the spinal cord and the nerve roots is essential. PMID- 1641926 TI - Lumbosacral disease. AB - Careful clinical and neurologic evaluations are the foundation on which a diagnosis of lumbosacral disease is based. Appropriate use of ancillary diagnostic aids will confirm the diagnosis and allow appropriate treatment to be instituted. PMID- 1641927 TI - Myelitis and meningitis. AB - Animals with meningomyelitis have clinical neurologic signs that typically range from paraspinal discomfort to tetraplegia; however, most affected animals also show evidence of multifocal CNS involvement with brain stem and cerebral cortical structures being affected most commonly. The cause, duration, and host response to the disease process will determine the clinical signs in individual animals. Confirmation of a specific causative agent is difficult, but CSF analysis and immunotesting of serum and CSF yield the most rewarding diagnostic results. Successful treatment is based on formulation of an appropriate and aggressive therapeutic regimen. In some diseases, no effective treatment is available, and some animals may develop permanent neurologic disabilities. PMID- 1641928 TI - Degenerative myelopathy. AB - DM in the German Shepherd is an immune-related disorder whose clinical signs are explained by a widespread degeneration of the white matter pathways in the thoracolumbar spinal cord. Therapy includes exercise, vitamin supplementation, and EACA medication. Avoiding unnecessary surgical procedures is also important to preclude permanent deterioration that can result following surgery in DM patients. In dogs other than German Shepherds, other identifiable causes should be treated. Additional confirmation of the diagnosis of DM may be assisted by performing cell-mediated immune studies or other serodiagnostic tests as they become available. PMID- 1641929 TI - Neoplasms of the spine. AB - Although the treatment of central nervous system neoplasms generally is unrewarding, some animals with spinal neoplasia may, for a variety of reasons, be successfully managed for extended periods of time. The veterinary profession has greater experience with spinal surgery than with intracranial surgery. As a result, surgeons are more willing to attempt and more successful at removing or debulking spinal neoplasms. Additionally, there are more affordable and accessible diagnostic procedures available to evaluate the spinal cord than there are to evaluate the brain. Finally, the majority of tumors that affect the spinal cord are extramedullary and are therefore amenable to attempts to remove them surgically. PMID- 1641930 TI - Congenital spinal malformations. AB - When presented with an animal that has a congenital spinal malformation, the veterinarian needs to consider the clinical significance of the malformation, the possible presence of other anomalies--spinal and nonspinal, the heritability of the malformation, and potentially innovative treatment options. This article includes explanations of the conditions and information regarding diagnosis and treatment of hemivertebrae and block vertebrae, malformations at the cranial vertebral junction, osteocartilaginous exostoses, spinal bifida, and spinal stenosis. PMID- 1641931 TI - [Morphologic and cytochemical study of Sertoli cell nuclei in ruminants]. AB - Nuclei and nucleoli were examined at an ultrastructural level in the testicular tissue of bulls and rams. In the two species there occurs a morphologically interesting so called multivesicular nuclear body; the interpretation of its function is not quite clear. The tissue was processed by a routine electron microscope technique and than a cytochemical demonstration of several types of proteins was used. Acidic argyrophilic proteins were demonstrated by a silver staining technique, basic lysine-rich proteins by means of ethanolic PTA, and ribonucleoproteins (RNP) by the method of Bernhard's regressive preferential staining. Multivesicular nuclear bodies in bull Sertoli's cells are composed of a greater number of membrane bound vesicles with granules on the outer surface (Fig. 1). The results of cytochemistry reactions show that the granules contain acidic argyrophilic proteins (Fig. 3) and RNP (Fig. 7). The intervesicular material is an analogy of the dense fibrillar component of normal nucleoli of somatic cells. This component contains the three types of investigated proteins (Figs. 2, 3, 5, 7). In the nuclear bodies of ram Sertoli's cells the number of vesicles is much lower, the fibrillar component is prevailing, in form of clusters and striae of filamentous material around the vesicles. The cytochemistry reactions proved that this material contains acidic argyrophilic proteins (Fig. 4) and basic PTA positive (Fig. 6) proteins. The presence of acidic and basic regulatory proteins in the fibrillar component of multivesicular nuclear bodies indicates the active synthesis of RNA occurring in this material. It is therefore possible to consider this special type of nuclear bodies as a full equivalent of nucleoli of somatic cells as to the function. PMID- 1641932 TI - [Effect of monensin (USA, Czechoslovakia, Bulgaria) on fermentation of animal feed in an artificial rumen (Rusitec)]. AB - An experiment was made with the Rumen Simulation Technique (Rusitec) in which the fermentation of a mixed ration of hay (12.8 g/d) and bruised barley (3.2 g/d) was compared with the fermentation of the same diet in the presence of 5 mg monensin/d from the USA, CSFR and Bulgaria. The fermentation of the mixed ration was significantly affected by all three kinds of monensin. The digestibility of dry matter (DM) in the rations declined in the presence of monensin from 48% to 40% (tab. I). The digestibility of detergent fibre, cellulose and hemicellulose also declined in the presence of monensin (tab. I). The production of methane decreased (-70%) and CO2 production dropped too, but this decrease could be accounted for by the changes in the production of volatile fatty acids and redistribution of metabolic hydrogen (tab. I). Monensin decreased the production of total volatile fatty acids (-21%), the production of acetic (-35%), n-butyric, n-valeric and isovaleric acids (tab. II) and increased the production of propionic acid (+60%). The production, utilization and recovery of metabolic hydrogen were significantly increased in the presence of all three kinds of monensin (tab. IV). The end products of fermentation were affected by an addition of monensin to the mixed ration. All three kinds of monensin increased energic efficiency of volatile fatty acids, decreased adenosinetriphosphate (ATP) production, the amounts of fermented hexose, organic matter fermented and utilization of glucose (tab. III).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641933 TI - [Tests of Milkofix, a new preservative preparation for milk samples used for infrared analysis of milk components. I. Verification of its bacteriostatic and bacteriocidal effects and its interference effects]. AB - Hygienic, ecological and health problems of sample preservation for an analysis of basic milk components make us continually to develop a safer chemical preservative substance which will preserve the original sample composition for the time required and which will not influence the analyses. Trzicky (1990) proposed Milkofix (M), a preservative substance on the basis of silver compound. The author reports on minimum risks of the use of this preparation, in comparison with traditional preservatives. Preservative efficiency of Milkofix was compared with other preservatives: K2Cr2O7 (C), NaN3 (A) and bronopol (B). The following concentrations were used: A--0.0085 g NaN3 and 0.0630 g NaCl, B--0.0050 g bronopol and 0.0500 g NaCl, C--0.0330 g K2Cr2O7 and 0.0670 g KCl in tablet, M- 0.1250 g of the mixture, all amounts are per 25 ml milk. The observed antibacterial efficiency of M could be seen in a slower decrease in actual acidity, and/or in an increase in titratable acidity in M-treated samples unlike untreated ones (N). From the starting value pH 6.3 (Fig. 1), the value of N treatment dropped to 3.8 after two days, the values of M and A treatments dropped to 4.9 after nine days and to 5.7 after twelve days, respectively. As for SH, the values increased within the same interval from 6.5 (2.5 mmol/l) to 28.6 in N, and to 22.3 in M and 9.4 in A (Fig. 3). There was a similar trend when the milk samples were stored at a temperature of 4 degrees C, but the differences between the preservation methods were not so clear in comparison with storage at a temperature of 20 degrees C (Figs. 1 and 3). The standardized SH value of 9.0 (2.5 mmol) for infraanalyzer measurements was exceeded after 24 hours in N samples, after four days in M samples and after 12 days in A samples at a temperature of 20 degrees C. The observation of the growth of microorganism counts (CPM) showed that this growth was slower in M than in N, but faster in the samples of C treatment (Fig. 5). The generative time of CPM in N made 1.6 hours, in M 2.4 hours and in C 7.9 hours. The lag phase of these mixed cultures was 24 hours in M, 60 hours in C and in N treatment the lag phase was zero.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1641934 TI - [Testing Milkofix, a new preservative preparation for milk samples used for infrared analysis of milk components. II. Verification of its preservative effects in relation to infrared analysis]. AB - For the purposes of the infrared analysis of the basic milk composition, Milkofix, an ecologically friendly preparation used for milk sample preservation (Trzicky, 1990), was compared with untreated samples (N) and with samples preserved with sodium azide (A), bronopol (B) and potassium dichromate (C) at a storage temperature of 20 degrees C (I) and 4 degrees C (II) in samples kept for 14 and 18 days. Pursuant to the recommendations cited in literature, the preservatives had these concentrations: A = 0.0085 g NaN3 and 0.0630 g NaCl; B = 0.0050 g bronopol and 0.0500 g NaCl; C = 0.0330 g K2Cr2O7 and 0.0670 g KCl; M = 0.1250 g, all amounts are per 25 ml milk. Three bulk milk samples were used which were analyzed on an automatic Milko-Scan 133 B infraanalyzer (Foss Electric, Denmark) every day. On the basis of a graphical evaluation of the results by IDF recommendations (1985) the times within which the applicable results could be obtained were determined for the various methods of milk sample treatment (Figs. 1 to 6): N I--0 days; A I--9; B I--10; C I--13; M I--4; N II--10; A II--5; B II- 11; C II--15; M II--10 (Tab. I). The results recorded for Milkofix are in agreement with the conclusions drawn in the previous study, where the intervals of four and nine days were determined. The days to milk sample coagulation were as follows: N I--1 day, M I--10 days. The coagulation in A I, B I, C I and N II samples was not observed even after 13-day storage and in A II, B II, C II and M II samples not even after 17 days of storage. The results for particular components (fat, proteins, lactose) of milk samples differently treated in time are presented in Tabs. II, III and IV. A system of evaluating criteria (Tab. V) was used to determine the order beginning from the most convenient method of milk sample treatment for the given purpose: 1. C II, 2. C I, 3. B II and A I, 4. B I, 5. M II, 6. N II, 7. A II, 8. M I and 9. N I.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1641935 TI - [Ultrastructure of boar sperm membranes prepared by freeze-fracturing]. AB - The objective of the present paper was to describe the topographic orientation of intramembraneous particles (IMP) in the membranes of freshly ejaculated boar spermatozoa applying the method of freeze fracturing. Disc clusters of IMP's could be distinguished in the acrosome-covering plasma membrane (PF). The border of the head to a distance of about 0.3 micron seemed to contain no IMP's (Figs. 1, 2). In the postacrosomal region in an anterior direction from the posterior ring the IMP's were found to be arranged in palissade slant rows. Statistical measurements of 20 spermatozoa (Tab. I) indicated that the slant rows extended to the greatest distance in the lateral part of the head, up to 0.67 micron (+/- 1.45-0.39) from the posterior ring. In the middle of the head the rows extended to a distance of 0.18 micron (+/- 0.10-0.42). The transition spot between the zone of sparse IMP's and the zone of densely arranged IMP's was at a distance of 1.63 microns (+/- 1.87-0.69) in an anterior direction from the posterior ring (Figs. 3, 4). In the flagellum in the plasma membrane (PF) the first spot of an ample occurrence of IMP's is located in the first mitochondrion in the spiral. The IMP clusters follow the cicumferential orientation of mitochondria in the mitochondrial spiral. The IMP's were missing in the spaces between the spiral coils (Fig. 5). The membranes of the mitochondria contain a large amount of IMP's. This activity is transferred to the clinging part of the plasma membrane (Fig. 6). A larger accumulation of IMP's can be seen at the spot where the plasma membrane covers the annulus (Fig. 7). In the plasma membrane of the main segment of the flagellum the IMP's are distributed irregularly in PF, and also in EF (Fig. 8). The EF surfaces of the plasma membrane had in general an indistinct structural organisation of IMP's. The distribution of IMP's in acrosomal membranes was found to be irregular. The postacrosomal lamina in the freeze fracturing did not look like a morphologically identifiable structure. In the nuclear envelope delimiting the posterior nuclear space, nuclear pores could be identified (Fig. 9). No nuclear pores could be seen in the nuclear envelope clinging to the posterior part of the nucleus. At this spot smaller IMP's were observed which could be a part of the proteins of the filaments connecting the concave surface of the head with the convex articular surface of the flagellum. These filaments connect the head and the flagellum (Fig. 10).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1641936 TI - [Diagnosis of sarcocystosis in sheep using the indirect fluorescence test and ELISA]. AB - The indirect fluorescent antibody test (IFAT) was compared with the enzyme-linked immunosorbent assay (ELISA) for the detection of specific antibodies to Sarcocystis sp. A set of 275 ovine blood samples was examined by both reactions. Cystozoites of Sarcocystis gigantea were used as the corpuscular antigen for the IFAT. For the diagnostics of sarcocystosis by the ELISA technique used the sandwich test of the antibody titration with a soluble antigen which was also prepared from S. gigantea macrocysts. Our studies confirmed that this antigen did not cross-react with Toxoplasma gondii. Titre 40 was determined as the limit one for the IFAT and titre 80 for the ELISA; which was confirmed by the direct detection of cysts in the muscles (Svobodova, 1989). The results of both methods are shown in Table I. 76.7% of the blood samples reacted positively in the IFAT and 83.6% in the ELISA. These methods were found to be suitable and can be utilized for the intravital routine diagnostics. PMID- 1641937 TI - [Metabolic indicators in large-scale breeding of goats during various seasons]. AB - Thirty-five biochemical parameters were investigated in 144 clinically healthy goats throughout the seasons of the year from March 1984 to April 1986. The average values and standard deviations of the investigated parameters of metabolic profile which are presented in this paper were obtained from examinations performed throughout the whole period of investigation. The average values of biochemical parameters are presented in Tabs. I and II. Our study of the values of the given parameters in the large-scale breeding of goats throughout the seasons of the year did not show a clear seasonal dependence of any of the investigated parameters with the exception of vitamin A and beta carotene contents. The average values and standard deviations of vitamin A and beta-carotene contents recorded throughout the year seasons are shown in Tab. III. Based on the average, and also individual values, it can be seen that the lowest levels of vitamin A were recorded at the beginning of the spring season (before the goats began to graze). In the winter seasons of 1984 and 1985 there were only traces of beta-carotene in the blood serum. A relatively great variance of the values mentioned by different authors demonstrates their great variability, which is influenced particularly by different environmental conditions, various methods of investigation, different nutrition and exploitation of the animals. PMID- 1641938 TI - [The effect of estrogens on phagocytic activity of blood leukocytes in heifers and cows]. AB - Phagocytic activity of peripheral leucocytes (PA) was measured in heifers during the luteal phase and oestrus and after administration of various doses of oestradiol, in ovariectomized heifers and cows in the early post-partum period. PA was demonstrated in 22.63 +/- 2.49% and 50.61 +/- 3.76% of phagocytes in the luteal phase and oestrus respectively (P less than 0.01, Fig. 1). The phagocytic index (PI) rose parallelly from 2.26 +/- 0.31 to 6.55 +/- 0.64 particles per cell (Fig. 2). Intramuscular administration of a single dose 3 mg of oestradiol dipropionate resulted in an increase of PA from 28.93 +/- 3.34 to 69.60 +/- 3.32 on post-treatment day 3 (P less than 0.05, Fig. 3). A nonsignificant increase of PA was observed in heifers treated with 10 mg oestradiol. Increases of PA and PI in postparturient cows, treated with various doses of oestradiol, were nonsignificant (Fig. 5, 6) owing to a wide variance of the values obtained, which might be due to individual differences in endocrine and metabolic status or to uterine bacterial contamination. The most marked of haematological changes was the increase of eosinophil counts from 317 to 525.10(6).l-1 in a group of cows treated with 10 mg oestradiol and a decrease of the lymphocyte: neutrophil ratio (Tab. I). Both endogenous and exogenous oestrogens stimulate PA of peripheral leucocytes and 3 mg of oestradiol is a sufficient dose to obtain the effect. PMID- 1641939 TI - [Development of rumen fermentation in calves during milk feeding]. AB - The concentration of total volatile fatty acids (VFA) in the rumen fluid were increasing with the age of the animals (Fig. 1). A significant increase in the concentrations of total VFA (P less than 0.01) from 70.93 to 90.71 mmol/l was observed in the age period of 5-7 weeks and a highly significant increase (P less than 0.001) in the age period of 9-11 age. At the average age of seven weeks the lower boundary of the reference value range (80-120 mmol) of the total VFA concentrations in the rumen fluid as mentioned for adult animals was exceeded in the experimental calves. As to this parameter in individual calves, the level of the total VFA concentrations in the rumen fluid of adult animals was not reached in 50% of calves at the age of three weeks, in 80% of calves at the age of five weeks, in 20% of calves at the age of seven weeks and in 10% calves at the age of nine weeks. At the age of 11 weeks the concentrations of total VFA reached the level of adult animals in all experimental animals (Fig. 2). The molar proportion of acetate (Fig 3) decreased from 74.04 mol% at the age of three weeks to 67.54 mol% at the age of 11 weeks, and the propionate proportion increased from 16.73 to 19.53 mol% within the same interval.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641940 TI - [Levels of insulin and glucose in calves during the first 6 months of life]. AB - Twenty-four calves of the Holstein-Friesian breed were included into a trial. The trial was performed from April (when the calves were born) to October. The objective of the study was to investigate variations in insulin and glucose levels over a longer time period of the postnatal development of calves. The blood was sampled by the jugular vein puncture at the age of 1, 2, 3, 5, 14, 21, 28, 35, 49, 63, 91, 118, 147 and 175 days. The calves were housed in a prophylactorium calf-house till the age of 21 days: till the age of 14 days they were housed individually and then in groups of 2-3 calves in a small pen. The calves were fed milk till the age of 26 or 28 days, after a fortnight the feed intake was increased from the previous 3 litres to 5-6 litres per head/day. At the age of 21 days the calves were transferred to pens in the calving room. At the age of 26 days twelve calves were transferred to a barn for young cattle rearing, the remaining twelve calves were transferred at the age of 28 days; here they were housed by 10-12 head per pen and they were fed a commercial milk replacer diluted at a 1:10 ratio, the feed intake being 6-8 litres a day, and a commercial pelleted calf starter TKS at the amount of 1.0-1.1 kg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641941 TI - [Comparison of the effectiveness of Milkofix, a preservative preparation, with traditional preservative agents in the determination of somatic cell count in milk samples using a fluoro-optic-electronic method]. AB - Milkofix (M), a health friendly preservative substance, to be used for milk sample preservation (Trzicky, 1990), was compared with other preservatives. Untreated milk samples (N) were tested against samples treated with sodium azide (A; 0.0085 g NaN3 and 0.0630 g NaCl), bronopol (B; 0.0100 g bronopol and 0.090 g NaCl), potassium dichromate (C; 0.0330 g K2Cr2O7 and 0.0670 g KCl) and Milkofix (M; 0.1250 g). The doses of the preservatives A, B, C and M are per 25 ml milk. The somatic cell counts (SB) were determined on a FOSSOMATIC 90 apparatus (FOSS ELECTRIC, DENMARK). In the treated milk samples taken from individual cows the values of SB counts were significantly higher than in N samples if determined within eight hours after sampling (Tab. I): in A higher by 18.6%, B by 26.3%, C by 26.4% and M by 24.3% (P less than 0.05). The significantly higher values of SB counts were recorded in bulk milk samples treated with preservatives in comparison with N samples immediately after sampling: in A by 6.0%, in B, C and M by 12.9% (P less than 0.01; Tab. II). After one-day storage of N samples at a temperature of 4 degrees C these differences are insignificant (P greater than 0.05), thus the results of N, A, B, C and M samples obtained after one-day storage at 4 degrees C can be taken as actual and mutually comparable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641942 TI - [The ovarian response and fertility in cows with acidosis induced by acetic acid]. AB - The effects of acetic acid administered at an amount of 300 to 600 g (5 to 10 mol) to the rumen of breeding cows, were investigated on ovulation, conception and progesterone levels in the blood and milk of cows with cloprostenol-induced (Oestrophan Spofa) oestrus at a dose of 500 micrograms i.m. In the group of 15 cows exposed to the acetic acid load five cows got in calf after the first insemination (33.3%), and 12 cows (80.0%) after all inseminations in 37.6 days after cloprostenol administration, with the insemination index 1.67 (Tab. I). In the control group (five cows) four cows (80.0%) got in calf after the first insemination, in total all five breeding cows got in calf in 20.6 days after cloprostenol administration, with the insemination index 1.2. In the experimental group of 15 cows a clinical examination of ovaries on day 7 after insemination revealed ovulation disorders in eight cows, that means in 53.3% of the animals (Tab. II). No ovulation disorders were observed in the control group of five cows. Progesterone levels in the blood showed high variability (Tab. III). In the group of cows administered acetic acid they were by more than a half lower (1.49; 0.67; 1.53 per ml) on days 7, 14 and 21 after insemination in comparison with the control group (3.35; 2.5; 3.38 ng per ml). The average progesterone levels in milk (Tab. IV) were 1.27 and 1.53 on day 7, 6.74 and 7.27 on day 14 and 3.52 and 11.85 ng per ml on day 21, respectively, the higher values apply to the control. It was not possible to evaluate reliably from the progesterone levels in the blood and milk if ovulation took place and if the corpus luteum was developing (Tab. V and VI). The clinical control of ovaries on days 7 and 8 after oestrus and insemination was more reliable to determine the ovulation disorders than the progesterone determination in the blood and milk of cows. PMID- 1641943 TI - [Characteristics of the cumulus-oocyte complex during the preovulatory period in superovulated heifers]. AB - The nature of cumulus--oocyte complexes was examined in PMSG (group 1, n = 18) and FSH (group 2, n = 30) stimulated heifers. Laparoscopy was performed 65 h after cloprostenol application. The number of follicles was 13.67 +/- 0.75 and 12.67 +/- 0.81 (P greater than 0.05) in group 1 and 2, respectively (Tab. I). The recovery rate of oocytes was 56% in the first and 67% in the second group (Tab. I). The cumulus oophorus was divided into three groups: compact, expanded and partial (Tab. II). Most oocytes (65 and 75% in the first and second group, respectively) exhibited an expanded cumulus (P greater than 0.05). In the first and second group 11 and 26% (P less than 0.01) of oocytes with the extruded first polar body were aspirated (Tab. III). As judged from the pool of visible follicles, the superovulation response to stimulatory treatment and recovery rate of oocytes in the present experiment were not different from the results published earlier. The degree of the cumulus oophorus expansion is an indicator for the evaluation of cumulus--oocyte complexes. After the preovulatory LH peak the disintegration of cumulus oophorus proceeds from glycosaminoglycan accumulation. In our experiment this effect resulted in a significantly higher number of oocytes with expanded cumulus in both treatments. The enlargement of perivitelline space is related to a subsequent release of the first polar body in the preovulatory period. It can be seen from our results that after FSH treatment it is possible to reach the high number of oocytes with the extruded polar body.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641944 TI - [The effect of aging of milk samples on the accuracy of infrared analysis of milk composition]. AB - The effect of a decrease (and/or fermentation) in the lactose content during milk storage under different conditions was investigated on the accuracy of the results obtained on a Milko-Scan apparatus to contribute to the present knowledge of this problem. The results were in agreement with some results cited in the literature. These wavelengths are used for infrared spectrophotometry on the above apparatus: for fat 3.48 microns, for proteins 6.46 microns and for lactose 9.60 microns. Bulk milk samples used for the tests were untreated or treated with potassium dichromate, bronopol, sodium azide and Milkofix at the temperatures of storage in darkness 20 degrees C and 4 degrees C. The differences against the reference values (measured on the first day) were determined and evaluated in milk composition and characteristics as arising during milk storage. These differences were used in form of either cumulative means of differences (Figs. 1 to 5) or individual differences (Fig. 8). In the first part significant correlation coefficients (P less than 0.001) were calculated for the relationship between the variations of lactose content and the fat and protein contents: r = 0.59 and/or -0.73 (Figs. 6 and 7). This suggests that the decrease in the lactose content by 0.10% recorded by the infrared analysis and caused by lactose decomposition is accompanied by a "seeming" increase in the fat and protein content by about 0.04%. In the second part the correlation coefficients for the fat and protein contents r = -0.96 and -0.96 (P less than 0.001; Figs. 9 and 10; Tab. II) were calculated on the basis of an observation of the lactose decrease in an untreated milk sample (20 degrees C for 28 hours). These coefficients are somewhat different from the preceding ones; this is due to the lower homogeneity of the first set where the milk samples were treated in a different way, but the coefficients confirm the same conclusions. The values of the correlation coefficients for the dependence between the development of the acquired titratable acidity (SH) and the variations of fat (F), protein (P) and lactose (L) contents were as follows: r = 0.95; 0.95; -0.99 (P less than 0.001; Figs. 12, 13; Tab. II). Thus the above-mentioned "seeming" increase in the F and P contents can be explained to the extent of 92.2% from the decrease in the L content, which also causes the increase in titratable acidity to the extent of 98.0%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1641945 TI - [The effect of Bentazone, a Czechoslovak developmental herbicide, on health status indicators in sheep during subchronic poisoning]. AB - A three-month feeding trial was conducted with sheep of the Slovak Merino breed (13-14 months of age, males and females) as a part of the obligatory toxicological tests of the Czechoslovak developmental herbicide bentazone (Research Institute for Chemical Technology, Bratislava). Partial results are shown describing the action of this herbicide on the overall health of sheep with respect to weight gains, trias values and intrauterine foetus development. The sheep of the first experimental group were fed bentazone as an additive to molasses feed M at a daily rate of 195 mg/kg lwt. (1/10 from LD50), and the sheep of the second group were fed a rate of 97.5 mg/kg lwt. (1/20 from LD50). No symptoms of the toxic effects of bentazone were observed in the course of the experiment. There were no differences between the experimental and test animals in the dynamics of pulse value changes (Fig. 1), breathing value changes (Fig. 2) and body temperature value changes (Fig. 3) from the beginning till the end of the trial. A slight increase in the pulse and breathing values above the upper reference value observed in the experimental groups in the last two to three weeks of the trial cannot be associated with the bentazone action. This increase reflects the physiological condition of the animals in the given conditions because the identical changes were also found in the control group. We assume that the changes were evoked by the elevated temperature of the external environment due to the fact that the sheep were not sheared.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641946 TI - [Surveillance of Francisella tularensis infection in dogs in Bratislava]. AB - Out of 548 serologically investigated dogs from Bratislava and other regions of Slovakia and Moravia, antibodies to F. tularensis were found in 16.4% (Tabs. I, II). In all the investigated groups of dogs from the region of Bratislava the highest seroprevalence by F. tularensis was recorded in watch dogs kept on farms and in cooperatives--37.5% and in rambling dogs--20.7% (Tab. I). The highest seropositivity was found in one to three year old dogs--22.2% (Tab. III). A similar degree of seroprevalence was also observed in one to three years old police dogs which came from the endemic region of tularemia--West Slovakia (19.3%) and East Slovakia (25.6%)--Tab. IV. These facts indicate the persistence of active natural foci in these regions. Serological investigations of the relatively great number of dogs from different regions of Slovakia showed that the presence of F. tularensis antibodies in this animal species, mainly in the watch dogs group, can be taken as a convenient marker or indicator of the existence of active natural foci of tularemia and as a suitable component for surveillance of this diseases. PMID- 1641947 TI - [Coxiella burnetii and Chlamydia psittaci infection in dogs]. AB - The prevalence of Coxiella burnetii and Chlamydia psittaci antibodies was investigated in 530 dog specimens divided into six groups, i. e. A = private watch dogs, B1 = service dogs from Bratislava, B2 = service dogs from other localities of Slovakia and Moravia, C = watch dogs from farms, I = household dogs, T = stray dogs. The dogs demonstrated the higher seropositivity to C. burnetii (11.7%) than to Ch. psittaci (5.5%). The highest percentage of antibodies to C. burnetii was found in stray dogs (23.7%), less prevalence of antibodies was observed in the animals in group C (13.6%), almost the same positivity was proved in the dogs of group B1 and B2 (10.5 and 10.6%). The highest positivity to Ch. psittaci was demonstrated in the dogs of group A (8.7%), less in group B2 (6.6%) and the least number in group B1 (1.9%). The stray dogs occupied the intermediate position in this data (Tab. I). Ninety four localities were tested, from which 38 were seropositive. Neither acute coxiellosis nor chlamydiosis were proved in any animals examined. Ninety per cent of dogs were found healthy, but 10% of dogs demonstrated hepatopathia and gastroenteritis. Two of them (category A and I) were seropositive to C. burnetii (titer 1:8 to 1:16) and one to Ch. psittaci (titer 1:16). Both C. burnetii and Ch. psittaci attack dogs parallely with the agents of other zoonoses, of which the most common is Toxoplasma gondii (Tab. II). Several dogs demonstrated seropositivity to three up to five zoonotic agents (Tab. III). PMID- 1641948 TI - [Leptospirosis in dogs in Slovakia]. AB - Out of 571 serologically investigated dogs from Bratislava and all regions of Slovakia and Moravia, 26.1% presented antibodies reacting with leptospiral antigens. The lowing seropositivity in dogs from Bratislava was found in lap dogs -11.1%, the highest one in farm dogs--35.3% (Tab. I). The seropositivity of police dogs from different regions of Slovakia and Moravia varied from 24.0% to 47.6% (Tab. II). The age of dogs progressing, their seropositivity rose from 3.1% in animals younger than one year to 33.3% in those aged seven years and in older ones (Tab. III). The predominant serovars causing infections of dogs were L. grippotyphosa (58.9% of infections) and serovars of both Sejroe (21.0%) and Icterohaemorrhagiae groups (15.3%). The serovars bratislava/jalna, pomond/mozdok and tarassovi were only rarely involved in these infections, canicola and arborea only exceptionally (Tab. IV). At present, in the Czechoslovak conditions the dogs do not play a significant role as reservoirs of human leptospirosis, and the predominant serovars may only cause irregular and short-time lasting leptospiruria. This is why the reasonableness of actual vaccination of dogs, possibly with the exception of the vaccination against Weil's disease, is doubtful. Dog is a good indicator of the distribution of different leptospiral serovars in its environment. It seems reasonable to practice occasionally serological investigations of these animals in order to detect possible changes in infecting leptospiral serovars. Consequently, adequate epizootological measures could be taken (e. g. modification of the composition of a leptospiral vaccine for dogs). PMID- 1641949 TI - [The physiology of natural parturition in cows]. AB - In the year 1990 free parturitions of 339 cows were followed on three farms; these parturitions were compared with the last parturitions of these cows when the tender's assistance was available. The spontaneous free parturitions were followed in the open air in litter boxes which were located outside the barns where the groups of about twenty highly pregnant cows and heifers were housed for two months before their parturitions all the year round irrespective of the weather conditions. In addition to direct continuous observations, a host of zooveterinary data filed for these groups of animals were evaluated, concerning particularly those animals which could not be directly followed for the time reasons. Through direct observations the time schedule of the given parturition was evaluated and recorded above all, including all changes in the behaviour of the cow itself, and also behavioural changes in the group of animals or the behaviour of particular groups of animals toward each other. Applying the same criteria, the behaviour of born calves toward the mother, behaviour of calves toward each other and their behaviour toward other breeding cows was evaluated. The method of disinterested observation was used, this means the principle of noninterference with the most actions observed, with the exception of such situations that could result in the calf death. Another principle was to minimize through these observations all negative effects that could influence the behaviour of individual animals and also the behaviour of the whole group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641950 TI - [Use of the skin test in the evaluation of true levels of cellular immunity and levels after experimental administration of glucan and levamisole in feed-lot bulls]. AB - Applicability of a skin test induced by dinitrofluorobenzene (DNFB) to quantification of the actual level of cellular immunity (CI) in vivo and its level after an experimental immunomodulation intervention were evaluated in two breeds (40 animals in each) of fattening bulls (10-11 months old). At the selected methodical procedure of intensity determination of the delayed type of hypersensitivity (DTH), its average value reached 4.5 +/- 1.5 mm in 80 animals, while in 77.5% of bulls its level ranged from 3.6 to 9.6 mm, in 18.7% from 2.0 to 3.5 mm and in 3.8% remained less than 2.0 mm. Evident expression of the reaction points to the possibility of application of the used methodical procedure of the skin test using DNFB to quantify the level of CI response in vivo in cattle. Percentual representation of animals according to the intensity of skin reaction (Tab. I) and concentration of total serum immunoglobulins (Cs-Ig) and serum IgG (Tab. II) indicates the different cellular and humoral state of animals in investigated breeds. This is also confirmed by the recorded average values of mentioned parameters which were significantly lower (P less than 0.01; or 0.05) in animals of the first breed (4.0 +/- 1.3 mm; 28.3 +/- 4.4 U ZST, 18.4 +/- 3.5 g.l-1) than in breed 2 (4.9 +/- 1.6 mm; 32.5 +/- 3.8 U ZST; 20.3 +/- 3.5 g.l-1). The animals of each breed were divided into four experimental groups with the approximately equal actual levels of DTH (Tab. III).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641951 TI - [Isolation and control of the functional quality of mRNA of bovine leukocyte interferon]. AB - For the construction of the cDNA library total cellular RNA was separated from bovine leucocytes induced with NDV (inductor of interferons) for five hours. Guanidinisothiocyanate and ultracentrifugation in the gradient of CsCl were used for the separation of the total RNA (Chirgwin et al., 1979). Bands 18S and 28S were detected in the samples of RNA by electrophoresis in an MOPS buffer (Fig. 1). mRNA was separated from the mixture of RNA via affinity chromatography on oligo(dT)-cellulose (Aviv and Leder, 1972). The function quality of mRNA BoIFN alpha was verified by microinjection into the oocytes of Xenopus laevis using a microinjector of our own construction (Fig. 2). The microinjector was calibrated by injection of a radioactive 51Cr solution (Fig. 3). It was found out on the basis of CPE inhibition measurements that the injected oocytes synthesized 320 640 U/ml BoIFN-alpha (16-32 U/50 microliters; Tab. I). PMID- 1641952 TI - [The effect of copper and cobalt supplementation on the digestibility of fibrous feed in sheep]. AB - The effects of an addition of copper, cobalt, and copper + cobalt on the in vitro digestibility of hay, treated beech sawdust and cellulose by the rumen fluid of sheep fed a complete food ration, complete food ration with 15% treated beech sawdust and a diet consisting of 80% hay and 20% barley were investigated, respectively. The rumen fluid obtained from animals fed a complete food ration showed the significantly higher digestibility of hay (Tab. I) when Cu (P less than 0.05), Co, or Cu + Co (P less than 0.001) had been added into the rumen. The cellulose digestibility increased only after Co application (P less than 0.05). The microelements supplementation in all three forms had a very significant effect on the digestibility of treated beech sawdust by the rumen fluid of sheep fed a diet with 15% sawdust content, although the initial digestibility by the rumen fluid in the control animals (without microelements) was only 44.9%. A similar trend was also observed in the cellulose digestibility, but after Co application this increase was not significant. The rumen fluid of animals fed hay (80%) and barley (20%) showed the highest digestibility. The digestibility of sawdust reached 60% and the of cellulose 95.9% without microelements supplementation (control). In this case the effect of microelement supplementation on the sawdust digestibility was manifested only in the case of cobalt by the digestibility decrease (P less than 0.001). The cellulose digestibility also decreased after administration of Cu (P less than 0.01) and Co (P less than 0.05). The Cu + Co supplementation did not influence its digestibility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641953 TI - [Levels of mercury in the organs and tissues of sheep after administration of very low doses]. AB - Experiments were carried out with six sheep of the Slovak Merino breed, weighing 22-28 kg. For 28 days the animals were given 4 mg inorganic Hg2+ in the feed per animal/day. In contrast with the controls, the following residual mercury concentrations were determined in the single organs and tissues: liver 1.580 +/- 0.326 mg.kg-1 Hg2+ and 0.091 +/- 0.014 mg.kg-1 Hg2+, respectively muscle 0.064 +/ 0.009 mg.kg-1 Hg2+, and 0.026 +/- 0.006 mg.kg-1 Hg2+, resp. spleen 0.142 +/- 0.025 mg.kg-1 Hg2+, and 0.022 +/- 0.010 mg.kg-1 Hg2+, resp. kidney 9.054 +/- 3.794 mg.kg-1 Hg2+, and 0.128 +/- 0.080 mg.kg-1 Hg2+, resp. (Fig. 1), abomasal contents 0.309 +/- 0.069 mg.kg-1 Hg2+, and 0.021 +/- 0.007 mg.kg-1 Hg2+, resp. large intestinal contents 0.267 +/- 0.058 mg.kg-1 Hg2+, and 0.043 +/- 0.004 mg.kg 1 Hg2+, resp. The results suggest that the long-term ingestion of mercury with feed leads to a pronounced Hg accumulation in the kidneys and liver. Much lower levels were observed in the muscle tissue and spleen. The affinity of mercury to the kidney and liver is probably related to the preferential bonds of organic mercury compounds to the SH- groups of the plasma proteins in these organs. It is the bond to the sulphydryl groups of proteins that results in the inhibition of proteosynthesis and thus enzyme and antibody inhibition. Under the conditions of continuing chemical contamination of the environment, a permanent supply of low concentrations of heavy metals the animal organism is observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641954 TI - [Clinical effects and morphological changes after administration of low doses of ochratoxin A to broiler chicks]. AB - Ochratoxin A (OA) was fed to HYBRO broiler chicks at a relatively low levels of 850 micrograms/kg up age 42 days. The effects of OA on chick development, health state and the patho-morphological lesions in internal organs were investigated in this experiment. The chicks exposed to the relatively low OA levels were observed to lag behind in their growth; this was confirmed by their regular weekly weighing when the lower liveweight in comparison with the control group was recorded from the age of 14 days. A decrease in the liveweight was statistically significant at the age of 21, 28 and 35 days. The patho-anatomic finding was negative. A histological examination of kidneys and liver revealed the pathological lesions typical for ochratoxicosis. The lesions observed included the dystrophy of the tubular epithelial cells (Fig. 1), eosinophil granules in the tubulus lumen (Fig. 3), dystrophic lesions in the glomerules (Fig. 2) and cellulization of the connective tissue of intertubular spaces (Fig. 1). The lesions of liver (Fig. 4) show to allergic responses and defense reactions of the organism to the OA action. On the basis of results it can be concluded that the relatively low ochratoxin levels cause histopathological lesions in the kidneys and liver of chicks, and in this way they can negatively influence their development and performance. PMID- 1641955 TI - [Use of xylazine and ketamine in the induction of halothane anesthesia in dogs]. AB - Our experience of the administration of xylazine and ketamine for an induction of halothane inhalation anaesthesia in dogs is described in this paper. After this procedure had been evaluated in 10 test dogs, the xylazine-ketamine induction was used for different surgical interventions in 160 patients. After joint i.m. atropine (0.05 mg/kg) and xylazine (1.5-2 mg/kg) pre-medication general anaesthesia of the dogs was induced by an i.v. administration of 1% ketamine (2 mg/kg). After intubation and anaesthetizer connection halothane vapours had to be applied for 2 to 8 minutes at a 2.5% to 3.5% concentration to induce the tolerance stage of anaesthesia. Then the anaesthesia level was maintained by an application of halothane vapours at a 0.5 to 1.5% concentration (Tab. I). In addition to an evaluation of the anaesthesia proper, breathing-rate, inspiratory and expiratory volumes, internal body temperature were recorded, ECG was made and venous blood samples were taken to evaluate acid-base balance changes. The processing of the obtained data (Figs. 1 to 5, Tab. II) revealed a transient breathing attenuation after the xylazine-ketamine induction and partly compensated respiratory acidosis. On the basis of our results this tested method can replace the traditional thiopental induction associated with the risks of cardiopulmonary depression, or even blood circulation stoppage. PMID- 1641956 TI - [Focal changes in the lungs of wild hares caused by the parasite Protostrongylus commutatus (Diesing, 1851)]. AB - The pathomorphological changes in the lungs of hare (Lepus europaeus Pallas, 1778) provoked by the parasite P. commutatus (Diesing, 1851) are macroscopically manifested as layer and nodular changes. With regard to the fact that the layer changes are suggesting the hatching nodules of protostronglyoses of small domestic ruminants, we have decided to rate them separately because of the differentiation. The layer changes on the surface of hare's lungs become evident as areas of emphysema, inflammation and induration. The emphysematous changes are macroscopically evident in the form of lobular formation (Fig. 1). Histologically, it was found out that the emphysematous effect was limited by an area of compressed lungs structures without perspicuous signs of the development of atelectatic changes (Fig. 2). The emphysematous changes are causing prominent exudative inflammatory processes in the bronchi and bronchioli provoked by unfertilized and disintegrating eggs of parasites. Inflammatory layers are macroscopically evident as solid brown-reddish areas (Fig. 3). Their macroscopic manifestation is transient. It is qualified by the stages of the inflammation itself. It is possible to put down the stage of manifestative development of the changes in the inflammatory areas only by continual examinations of hare's lungs all year round. Unfertilized eggs and grounded, disintegrating larvae of protostrongylus are provoking the inflammatory reactions which may lead in the layer changes to the obliteration of bronchioli (Fig. 6), which is macroscopically evident as induration (Fig. 7). The bronchioli are obliterated so that the phagocytic ability of monocytes is transformed to a reparative ability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1641957 TI - Chronic tracheobronchial syndrome in eight dogs. AB - Chronic tracheobronchial syndrome was diagnosed in eight dogs which had had a chronic mild cough for two to 13 months but were otherwise clinically normal. In five of them there was evidence of contact with other coughing dogs before the appearance of clinical signs and the majority at first responded favourably to antibacterial therapy. The coughing occurred mainly when the dogs pulled on their leads or became excited. Three cases had bronchoscopic evidence of active airway inflammation, and five had varying numbers of inflammatory cells (neutrophils) in bronchial aspirates. There was no evidence of excessive production of mucus in the airways of any of the dogs. Seven had an increased bronchial pattern on radiographs but only one of the dogs has developed chronic bronchitis. PMID- 1641958 TI - Bovine spongiform encephalopathy: recent observations on the age-specific incidences. PMID- 1641959 TI - Retractile mesenteritis in a cat. PMID- 1641960 TI - Tests of four baits for oral vaccination of dogs against rabies in Tunisia. PMID- 1641961 TI - Mycotoxicosis associated with Penicillium purpurogenum in horses in Nigeria. PMID- 1641962 TI - Feline vaccination. PMID- 1641963 TI - Carcinoid in canine large intestine. PMID- 1641964 TI - Mare scanning--possible ectopic pregnancy. PMID- 1641965 TI - Clinical teaching: a case for treatment. PMID- 1641966 TI - Slowing the spread of anthelmintic resistant nematodes of sheep and goats in the United Kingdom. AB - Anthelmintic resistant nematodes pose an increasing threat to animal welfare and lamb production on lowland sheep farms in the United Kingdom. Based on published information on anthelmintic resistance in nematodes and insecticide resistance in arthropods, seven recommendations are made for reducing the development and spread of anthelmintic resistant nematodes. The two most important are probably to prevent the introduction of resistant worms through the purchase of stock and to reduce the reliance on frequent anthelmintic treatments by using epidemiological principles of nematode control. PMID- 1641967 TI - Pharmacokinetics and bioavailability of spiramycin in pigs. AB - The pharmacokinetics of spiramycin in pigs were investigated after intravenous and oral administration. The potential therapeutically effective blood level was established after a single administration and examined in a subsidiary five day study. The rapid intravenous injection of 25 mg spiramycin/kg bodyweight produced marked salivation in all the test animals. The elimination half-life (2.3 +/- 1.2 hours) was relatively short, in accordance with the total body clearance rate (27.3 +/- 10.1 ml/minute/kg). The high volume of distribution (5.2 +/- 2.2 litres/kg) was due to the accumulation of the drug in the body tissues. The maximum plasma concentration (4.1 +/- 1.7 micrograms/ml) after oral administration of 85 to 100 mg spiramycin/kg bodyweight was reached after 3.7 +/- 0.8 hours and the half-life of the elimination phase was 6.0 +/- 2.4 hours. The oral bioavailability was 45.4 +/- 23.4 per cent. Ad libitum feeding of a diet containing 2550 mg spiramycin/kg produced a steady state concentration of 0.96 +/ 0.27 micrograms/ml. This plasma concentration would provide a potentially therapeutically effective blood concentration against Mycoplasma species, Streptococcus species and Staphylococcus species. PMID- 1641968 TI - Effects of blue-eared pig disease on a breeding and fattening unit. PMID- 1641969 TI - Antibodies to phocine distemper virus in Canadian seals. PMID- 1641970 TI - Coronal cemental hyperplasia in a cow. PMID- 1641971 TI - Availability of medicines. PMID- 1641972 TI - Docking of dogs. PMID- 1641973 TI - Ewe deaths. PMID- 1641974 TI - Correlation of RNA secondary structure and attenuation of Sabin vaccine strains of poliovirus in tissue culture. AB - Part of the 5' noncoding regions of all three Sabin vaccine strains of poliovirus contains determinants of attenuation that are shown here to influence the ability of these strains to grow at elevated temperatures in BGM cells. The predicted RNA secondary structure of this region (nt 464-542 in P3/Sabin) suggests that both phenotypes are due to perturbation of base-paired stems. Ts phenotypes of site directed mutants with defined changes in this region correlated well with predicted secondary structure stabilities. Reversal of base-pair orientation had little effect whereas stem disruption led to marked increases in temperature sensitivity. Phenotypic revertants of such viruses displayed mutations on either side of the stem. Mutations destabilizing stems led to intermediate phenotypes. These results provided evidence for the biological significance of the predicted RNA secondary structure. PMID- 1641975 TI - Transcriptional activation of the tat-defective human immunodeficiency virus type 1 provirus: effect of interferon. AB - The effect of human interferon-alpha 2 (HuIFN-alpha 2) on the activation of HIV-1 provirus was studied in cell lines containing either an integrated tat-defective HIV-1 provirus (HIV-1 (-tat)) (HNHIVdt4 cells) or the HIV-1 (-tat) provirus and a plasmid in which the expression of HuIFN-alpha 2 was under the control of HIV LTR (HNHIV alpha 1 cells). In both cell lines, the expression of HIV-1 RNA was below the limit of detection, but transcription of the HIV-1 (-tat) provirus could be induced either by transfection with Tat-expressing plasmid or by treatment with TPA and cycloheximide (CHX). By contrast, stimulation with TPA alone induced HIV 1 transcription only in HNHIVdt4 cells, but not in HNHIV alpha 1 cells that produced low levels of IFN-alpha constitutively. Similarly in a transient expression assay, TPA upregulated transcription of the transfected HIV-1 CAT plasmid only in HNHIVdt4 cells, but not in HNHIV alpha 1 cells. UV-crosslinking analysis of NF-kappa B-specific proteins induced in TPA-treated cells showed the presence of 45 and 55 kDa NF-kappa B-binding protein in TPA-induced HNHIVdt4 cells while, in HNHIV alpha 1 cells, we detected only 55-, 110-, and 200-kDa proteins, but no 45-kDa protein. The transcriptional effects of IFN could not, however, be seen in the presence of Tat protein, suggesting that the virus developed a mechanism to overcome the IFN-mediated restrictions. PMID- 1641976 TI - Increased E6/E7 transcription in HPV 18-immortalized human keratinocytes results from inactivation of E2 and additional cellular events. AB - We characterized the state of the viral genome and transcription of human papillomavirus 18 oncogenes, E6 and E7, in immortalized human keratinocytes. At passage 9 after transfection with HPV 18 a homogeneous population of immortal clones was present. These cells have the viral DNA integrated within the E2 orf, accompanied by its partial deletion, similarly to what has been found in cervical carcinoma specimens. Transcription of the E6 and E7 oncogenes is mediated by the major viral early promoter (P105). Interestingly, transcriptional activity from this promoter increased upon continued in vitro passage of the cells. This event is concomitant with an increase in the proliferation rate of the cells. Reintroduction of the HPV 18 E2 gene into these cells resulted in repression of P105. However, the amount of E2 was limited in the HPV 18-immortalized cells. These data suggest that both viral and cellular factors play a role in increasing levels of E6 and E7 transcription providing the host cell with a proliferation advantage necessary for tumor growth. PMID- 1641977 TI - Parvovirus B19 replication in human umbilical cord blood cells. AB - The human parvovirus B19 is now known to be one of the causative agents of nonimmune hydrops fetalis and spontaneous abortions in pregnant women. The presence of the viral proteins and antibodies in fetuses of B19-infected women suggests that the virus can cross the placental barrier. In order to gain an insight into the mechanism of intrauterine fetal infection and the virus-induced hydrops fetalis, we examined whether human umbilical cord blood cells were permissive for B19 replication. Cord blood cells were infected with B19 in vitro, and Southern blot analyses of low M(r) DNA isolated from these cells revealed the presence of the characteristic replicative intermediates of B19 DNA. In addition, B19 genome expression in cord blood cells was detected by Northern blot analysis. Quantitative DNA dot blot analysis of culture supernatants documented complete assembly and release of B19 progeny virions in these cells. The progeny virions were biologically active in secondary infections of normal human bone marrow cells. The human umbilical cord blood cells may be a useful alternative to bone marrow and fetal liver culture systems for further studies on B19 since the need for bone marrow donors is obviated and, unlike fetal tissues, there are no ethical questions associated with the experimental use of cord blood because it is normally discarded. These studies also suggest that the umbilical cord blood may be a site for active replication of parvovirus B19 in vivo and may thus provide a means for transmission of the virus during intrauterine fetal infections. PMID- 1641978 TI - Bacteriophage T4 gene 21 encodes two proteins essential for phage maturation. AB - The T4 prohead protease (T4 PPase) is the key enzyme in the morphopoietic pathway of the T4 phage head. It is responsible for the proteolytic processing of all head proteins allowing protein rearrangement and head expansion. To study its biochemistry and gene regulation, T4 gene 21 was cloned into an expression vector under the control of the inducible tac promoter. Two proteins of apparent molecular weights of 21.5 and 27.5 kDa were detected after induction. These proteins are synthesized using two different start codons in the same reading frame. Destruction of either start codon resulted in the loss of the respective protein. Complementation experiments with bacteriophage T4 21(-)-infected cells showed that both proteins are functional in vivo and essential for T4 phage assembly. PMID- 1641980 TI - Monoclonal antibodies recognizing normal and retrovirus-transformed chicken hematopoietic cells. AB - The avian hematopoietic system has long been an invaluable model to study the mechanisms of cell growth and differentiation. We have developed six MAbs against either chicken embryonic hematopoietic precursor cells or retrovirus-transformed cells. MAbs Mo1, Mo2, and Mo3 recognized transformation-associated markers expressed in AMV-transformed nonproducer cell line-BM2. Not only were these markers expressed 7 to 10 folds higher on BM2 than on normal monocytic cells, but their expression was drastically reduced when BM2 cells were induced to differentiate into macrophages by PMA. The control of marker expression is associated with v-myb-transforming cascade, since another monocytic lineage specific oncogene, v-myc, did not enhance the expression of these markers. MAb Em1 detected a marker that is normally present in 20% of the cells from the 30/50% interface of a discontinuous percoll gradient of normal 4-day-embryo yolk sac. Its expression is also found in AEV-transformed cells and MSB1 cells. The epitope for Em1 was exposed after neuraminidase treatment on erythroleukemia cell line 6C2, which suggested that sialylation and/or glycosylation is pivotal in regulating the expression of specific markers in differentiation pathways during embryogenesis and tumorigenesis. MAb Em2 recognized proliferating hematopoietic cells after the fourth day of embryogenesis. MAb Em3, on the other hand, is presumed to be specific for an oncofetal antigen expressed in various transformed cells but only in 10% of the cells from 30/50% interface of a discontinuous percoll gradient of normal 4-day-embryo yolk sac. These MAbs will be useful for dissecting the expression of differentiation markers within normal versus abnormal differentiation pathways in molecular terms. PMID- 1641979 TI - Proton nuclear magnetic resonance studies of the binding of sialosides to intact influenza virus. AB - The dissociation constants for binding of sialic acid derivatives to the hemagglutinin on intact influenza virus were determined using nuclear magnetic resonance (NMR) spectroscopy. The dissociation constants determined with whole virus are similar to, but slightly higher than, those determined with BHA (hemagglutinin released from virus by treatment with the protease bromelain; Sauter et al., 1989, Biochemistry 28, 8388-8396), indicating that the sialic acid binding site is not significantly altered when hemagglutinin is released from virus. Binding was quantified by observing the concentration-dependent broadening of the sialoside resonances in the presence of X-31 virus or alternatively by observing the effect of the sialoside on the resonances of a competitive "reporter" ligand. The glycosidic substituent attached to the sialic acid makes relatively little difference in the affinity of the sialoside for virus: alpha(2,6)-sialyllactose (KD = 2.7 mM) binds only slightly more tightly than alpha(2,3)-sialyllactose (KD = 3.5 mM). However, inversion of the glycosidic center produces a dramatic change in affinity: the dissociation constant for the alpha-methyl glycoside of sialic acid is 4.2 mM, but not binding is observed with the beta-methyl glycoside. PMID- 1641982 TI - The role of the tnv protein and tnv RNA splicing signals in replication of HIV-1 IIIB isolates. AB - The requirement for tnv, a tat-env-rev fusion protein expressed by the IIIB strain of HIV-1, was tested. The expression of tnv was prevented by altering the 5' splice site that flanks the central coding exon of tnv. Mutants that carry such an altered 5' splice site replicate normally in an established T-cell line and in peripheral blood lymphocytes, demonstrating that tnv has no effect on virus replication. However, two mutants that carry an alteration in the 3' splice site of the same exon are replication defective. The 3' splice site mutations result in significant reduction in the expression of the 16-kDa tat protein and induce the expression of large amounts of a 19-kDa rev-related protein that initiates within the central coding exon of tnv. S1 nuclease analysis reveals that splicing to the central tnv exon occurs with substantially increased efficiency via the use of an alternate 3' splice site six nucleotides 3' from the mutated site. The effect of the 3' splice site mutations on viral protein expression and replication are fully reversed by a second site mutation that eliminates the alternate splice site. PMID- 1641981 TI - Molecular analysis of a resistance-breaking strain of potato virus X. AB - Full-length cDNA clones of potato virus X (PVX) strains PVXUK3 and PVXHB have been constructed in plasmid vectors to allow in vitro transcription of infectious PVX RNA. In both instances the transcript-derived virus infected tobacco and potato identically to the respective progenitor strains: in tobacco and susceptible potato cultivars both strains infected systemically, producing symptomless or mild mosaic symptoms. In potato carrying the Rx or Nx resistance genes, the virus derived from the PVXHB cDNA infected systemically, whereas the virus derived from the PVXUK3 cDNA failed to infect the Rx plants or induced apical necrosis, characteristic of a hypersensitive response of the Nx gene. Three hybrid viral genomes were constructed at the cDNA level to localize the resistance breaking determinants of PVXHB. Transcripts of all three hybrids were infectious on tobacco. On potato cultivars with either the Rx or Nx resistance genes, the hybrid viruses infected in the same way as PVXHB, rather than PVXUK3. The common feature of these hybrid viruses, the coat protein gene, is therefore the determinant of Nx and Rx resistance breaking of PVXHB. PMID- 1641983 TI - Deoxyuridylate-hydroxymethylase of bacteriophage SPO1. AB - Phage SPO1 of Bacillus subtilis carries hydroxymethyl-deoxyuridylate in place of thymidylate in its DNA. The enzyme, responsible for the conversion of dUMP to HmdUMP, is a dUMP hydroxymethylase, encoded by the SPO1 gene 29. Here we describe the cloning and sequencing of the gene and the overexpression of the gene product. DNA hybridization using the DNA of bacteriophage T4 dCMP hydroxymethylase gene as a probe, allowed us to identify and map g29 on a 3.9-kb restriction fragment, EcoRI*11. We determined the nucleotide sequence. One of the open reading frames detected, coding for a putative 44.6-kDa protein, showed significant amino acid homologies with all known thymidylate synthases. Gp29 was overexpressed in the pT7 system. Extracts prepared from induced cells show hydroxymethylase activity in a tritium release assay. PMID- 1641984 TI - Peanut stunt virus satellite RNA: analysis of sequences that affect symptom attenuation in tobacco. AB - The V-satellite RNA (V-satRNA) of peanut stunt virus (PSV) has no effect on symptoms produced in tobacco by PSV. In contast, the G-satRNA induced complete or nearly complete suppression of systemic symptom development. Because G-satRNA differs from V-satRNA in only five nucleotide positions, these two satRNAs provide excellent material for investigating the molecular basis of satRNA mediated symptom attenuation. For this purpose, we constructed transcription vectors containing full-length cDNA clones from which infectious RNA transcripts can be synthesized in vitro, and produced chimeric and mutant satRNA molecules. Although an A----C substitution at position 362 of the V-satRNA molecule delayed systemic symptom development and reduced symptom severity, changes at both nucleotide positions 226 (C----U) and 362 (A----C) of V-satRNA were required for suppression of systemic symptom development. Our results are consistent with the idea that PSV satRNAs are noncoding molecules that exert their biological activities by directly interacting with host/viral components. PMID- 1641985 TI - The vaccinia virus K2L gene encodes a serine protease inhibitor which inhibits cell-cell fusion. AB - In certain circumstances, cells infected with vaccinia virus (VV) undergo fusion, but this does not occur in tissue cultures infected with wild-type VV. The VV genome includes three genes (B24R, B13R, and K2L) encoding polypeptides that are structurally related to members of the plasma serine proteases inhibitor (SPI) superfamily. In this study, we demonstrate by deleting these genes singly or in combination that the K2L gene encoding SPI-3, but not the B24R or B13R genes encoding SPI-1 and SPI-2, inhibits cell-cell fusion in VV-infected cells. A VV encoded hemagglutinin (HA) has previously been demonstrated to inhibit cell-cell fusion, but fusion-promoting VVs with K2L gene deletions had normal expression and cellular location of the VV HA. As both HA and SPI-3 independently inhibit cell-cell fusion in VV-infected cells, there must be at least two fusion promoting mechanisms encoded by VV. These may play different roles in virus-cell fusion and in cell-cell fusion after VV infection. PMID- 1641986 TI - Untranslatable transcripts of the tobacco etch virus coat protein gene sequence can interfere with tobacco etch virus replication in transgenic plants and protoplasts. AB - Transgenic tobacco plants which express untranslatable sense or antisense forms of the tobacco etch virus potyvirus (TEV) coat protein (CP) gene sequence have been generated. One of seven transgenic plant lines expressing a CP gene antisense transcript showed an attenuation of symptoms when inoculated with TEV. Three of ten transgenic plant lines expressing untranslatable sense transcripts did not develop symptoms when inoculated with TEV. These lines were resistant to either aphid or mechanically transmitted TEV. In contrast to CP-mediated resistance reported for other viruses, resistance was (1) mediated by an RNA molecule; (2) TEV-specific (i.e., "broad-spectrum resistance" was not observed); (3) independent of inoculum levels; (4) not dependent on plant size and; (5) due to decreased levels of virus replication. Protoplast experiments were used to demonstrate that resistant plant lines did not support the production of virus protein and progeny virus at wild-type levels. PMID- 1641987 TI - Selection of antigenically distinct variants of influenza C viruses by the host cell. AB - Five strains of influenza C virus were isolated and passaged in the amniotic sacs of embryonated hens' eggs, or in the HMV-II line of human malignant melanoma cells, and were tested for reactivity with a panel of monoclonal antibodies to the hemagglutinin-esterase (HE) glycoprotein. It was observed with two strains (C/Yamagata/4/88, C/Yamagata/7/88) that the HE of virus passaged in HMV-II cells was antigenically distinguishable from that of virus cultivated in eggs. Virus clones obtained after repeated passages of these two strains in HMV-II cells all showed a significant increase in the ability to replicate in the cell culture compared to clones derived from viruses grown in eggs. No difference was seen, by contrast, in the ability to grow in eggs between HMV-II- and egg-derived virus clones. It was also found that HMV-II-grown viruses but not egg-grown viruses could agglutinate glutaraldehyde-fixed chicken erythrocytes at 23 degrees. These observations, taken together, suggest that isolation and passage of influenza C virus in HMV-II cells sometimes result in selection of antigenically distinct variants which have an advantage in binding to the cell surface receptors. Sequence analyses of the HE genes revealed that compared to egg-grown viruses, HMV-II-adapted variant of the Yamagata/4/88 strain had a single amino acid substitution in the HE molecule at position 283 (Asp----Asn) and that of the Yamagata/7/88 strain had two substitutions at positions 212 (Glu----Lys) and 519 (Asn----Asp). PMID- 1641988 TI - Adenovirus helper function activity of simian virus 40 T antigen mutants. AB - The SV40 large T antigen provides a helper function that permits human adenovirus yields in monkey cells to approach those obtained in human cells. The carboxy terminus of large T antigen is involved in providing this activity. The ability of a large number of SV40 mutants affecting T antigen to enhance the growth of adenovirus type 2 in the CV-1 line of African green monkey kidney cells was examined. Mutation of those serines and threonines at the carboxy terminus which are normally phosphorylated had no effect on adenovirus helper function. A cytoplasmic T antigen was very effective in providing adenovirus helper function. Mutants that produce unstable T antigens provided helper function, but to a reduced degree. Finally, mutations in T antigen which permit it to interfere trans-dominantly with replication catalyzed by wildtype T antigen provided adenovirus helper function at wildtype levels. PMID- 1641989 TI - Baculovirus-expressed rabies virus M1 protein is not phosphorylated: it forms multiple complexes with expressed rabies N protein. AB - The rabies N, M1, M2, and G antigens have been expressed in Spodoptera frugiperda cells from single gene expression vectors or dual gene vectors (N/M1 or M2/G) using the baculovirus system. Although N protein was phosphorylated, no evidence for M1 phosphorylation was obtained. N-M1 complexes were formed in vivo using dual infections or the coexpression vectors, as well as in vitro in mixing experiments. The free or complexed rabies N and M1 proteins reacted with available monoclonal and polyclonal antibodies. By sedimentation analyses the N M1 complexes were shown to exist in multiple configurations. PMID- 1641990 TI - A single amino acid substitution in the hemagglutinin-neuraminidase of Newcastle disease virus results in a protein deficient in both functions. AB - Sequence determinations of the hemagglutinin-neuraminidase (HN) glycoproteins of a temperature-sensitive mutant of Newcastle disease virus and two sequentially selected revertants had previously shown that substitution at a pair of residues, 129 and 175, resulted in a deficiency in neuraminidase (NA) activity, which was partially restored by a third substitution at residue 193. To evaluate the role of the substitution at residue 175 in diminished NA activity, the mutation was introduced into HN and the protein expressed in COS cells. The mutated HN not only had minimal NA activity but also was unable to absorb chicken erythrocytes, even though it was transported to the cell surface in normal amounts, in an apparently antigenic form. Attachment function was restored to the protein by the introduction of the additional substitution(s) at 129 and/or 193. These results indicate that residue 175 influences not only NA activity but also receptor recognition. PMID- 1641991 TI - Comparison of the S RNA segments and nucleoprotein sequences of Crimean-Congo hemorrhagic fever, Hazara, and Dugbe viruses. AB - The S RNA segments of the nairoviruses Crimean-Congo hemorrhagic fever (CCHF) virus (Chinese isolate) and Hazara (HAZ) virus were cloned and sequenced from PCR products. The RNAs comprise 1672 and 1677 nucleotides, respectively, and each encodes a protein in the viral complementary strand (54.0 and 54.2 kDa, respectively). The deduced protein sequences show homology to each other and to the nucleoprotein of Dugbe (DUG) nairovirus, although both the CCHF and HAZ viral proteins are larger. Alignment of the nucleoprotein sequences of CCHF, HAZ, and DUG viruses show that the CCHF and HAZ sequences are somewhat more closely related to each other (60.0% identity) than either is to the DUG sequence (55.4 and 53.0% identity, respectively); 39.5% of residues are identical across all three proteins. The carboxyl-terminus of DUG N protein shows a 40-residue deletion relative to the N proteins of the other two viruses. PMID- 1641992 TI - Abutilon mosaic geminivirus double-stranded DNA is packed into minichromosomes. AB - An intermediate form of Abutilon mosaic geminivirus, a complex of viral double stranded DNA (dsDNA) and protein, was characterized by two different techniques. Cesium sulphate gradient centrifugation was used to show that the majority of this form comigrates with host chromatin. Micrococcus nuclease digestion experiments with isolated nuclei demonstrated that the viral dsDNA is organized in a manner comparable to that of host nucleosomes. Results from a previous electron microscopical work (Abouzid, A. M., Frischmuth, T., and H. Jeske, 1988, Mol. Gen. Genet. 212, 252-258) suggested to us that a part of the viral dsDNA must be free of nucleosomes. Whether this nucleosome-free space corresponds to the intergenic region which contains most of the promotor sequences and the putative origin of replication is discussed. PMID- 1641993 TI - Characterization of beet curly top virus subgenomic DNA localizes sequences required for replication. AB - Subgenomic viral DNA is accumulated in Nicotiana benthamiana and Beta vulgaris plants agroinoculated with the geminivirus beet curly top virus. The subgenomic DNA is more abundant in N. benthamiana and is distributed between two broad size groups in this host. Six unique examples, ranging in size from 887 to 1311 nucleotides, have been cloned from viral double-stranded DNA purified from N. benthamiana and analyzed by sequence determination. Deletions are distributed throughout most of the genome and only nucleotides 2946-410 are represented in all subgenomic DNAs. Comparison with a previously characterized subgenomic DNA suggests that cis-acting signals necessary for viral DNA replication are located in a predominantly intergenic region between nucleotides 2946-308. PMID- 1641994 TI - Mutagenesis of a hexanucleotide sequence conserved in potexvirus RNAs. AB - Biologically active in vitro transcripts were synthesized from a cloned cDNA of a defective RNA (D RNA) of clover yellow mosaic virus (CYMV) and were used to determine if a hexanucleotide motif (5'-ACUUAA) conserved in the 3' noncoding region of potexvirus RNAs is essential for accumulation of progeny D RNA in planta. Deletion of rearrangement of the entire hexanucleotide sequence in the D RNA resulted in no detectable accumulation of progeny D RNA when coinoculated with helper CYMV RNA. Single-base substitutions of the four central nucleotides of the hexanucleotide sequence revealed that viable D RNAs can tolerate single residue changes at positions 3 and 5 only. These results suggest that the hexamer motif is involved in the process of D RNA propagation. The hexanucleotide sequence was also identified in the negative strand of potexvirus RNAs in the regions proposed to represent subgenomic RNA (sgRNA) promoters. In addition, the hexamer motif is present in similar regions in carlavirus RNAs. The conservation of this hexanucleotide (in orientation and position) in potexvirus and carlavirus RNAs, which serve as templates for full-length negative-strand synthesis and sgRNA production, strongly suggests that it plays a functional role in the synthesis of viral RNAs. Taken together, our data support our previous proposal (Bancroft et al., 1991. J. Gen. Virol. 72, 2173-2181) that the hexanucleotide sequence acts as a cis element involved in synthesis of full-length negative sense viral RNA and further implicate the sequence in a similar role in production of positive-sense sgRNA. PMID- 1641995 TI - Management of injured in combats in Yugoslavia from June 1991 to February 1992. PMID- 1641996 TI - Management of the diseased during combat operations in Yugoslavia 1991-1992. PMID- 1641997 TI - Posttraumatic stress disorders and psychotherapeutic approach. AB - The paper deals with the problem of the posttraumatic stress reaction of the young members of the Yugoslav People's Army (18-26 years old) who took part in the war of 1991. This paper is based on the explorative research of 43 subjects who were exposed to traumatic events in Croatia and Slovenia. The following variables have been treated in the research: the features of traumatized persons, the level of the posttraumatic personality integration, symptoms, plans for future and interpersonal consequences of the traumatic experience. The results have shown that the basic problem of all the psychotraumatized persons is the split between the experience of destructive reality that exceeds the death itself and outwar reality ruled by the laws that affirm life. On the basis of these experiences, the psychotherapeutic approach has been established and named "The Construction of the Peer Supporting Network" the essence of which is to overcome the gap between the two experienced but opposite realities. PMID- 1641998 TI - Psycho-social causes and consequences of refugee military families. PMID- 1641999 TI - Health status evaluation of the reserve forces under normal and emergency conditions. PMID- 1642000 TI - Forensic-medical expertise of twenty four murdered citizens from Gospic and its surroundings. AB - The forensic-medical expertise of 24 predominantly carbonized bodies, that were found at Kukin Do was reported. The victims were from Gospic and its surroundings, who disappeared between October 16-18, 1991. The expertise involved the identification of bodies, injury classification, determination of tools by which injuries were inflicted as well as time when injuries were inflicted, and whether it was when the victims were alive or dead. At the time of expertise all bodies were in the state of advanced putrification, frozen and burned. In 18 cases, the larger or smaller parts of bodies lacked as the consequence of fire. Eleven persons were identified as the Serbs from Gospic and for thirteen persons the procedure of identification is still in process. In 21 persons while they were alive, injuries were done with: bullets, blade, pointed and blunt mechanical tools. In three persons, injuries were not found due to missing of the larger parts of bodies. After their death all corpses were burned, and in two persons bites of rodents were evident. PMID- 1642001 TI - Preventive medical protection in the Armed Forces of Yugoslavia during military conflicts. AB - Some experiences in preventive medical protection in the Armed Forces of the Yugoslav People's Army (Y.P.A.) in the blockade and combat operations in 1991 are presented. In garrisons which were in the total blockade the basic life-needs were threatened and in the same time personnel was exposed to combat operations of enemy forces. Owing to alterness and discipline of the whole staff the basic hygienic measures of health protection were maintained. In units which were engaged in combat operations the hygienic prophylactic measures were conducted based on our doctrinal principles in preventive medical protection. The decrease in the incidence of infectious diseases and lack of epidemics point to the successfully applied protection. The health service provided protection both of people and refugees and also a significant help was extended to the units of the Armed Forces. PMID- 1642002 TI - Replacement therapy with virus-inactivated plasma concentrates in von Willebrand disease. AB - In von Willebrand disease, the goal of treatment is to correct the two laboratory hallmarks of abnormal hemostasis, i.e. the deficiency of factor VIII (FVIII) and the prolonged bleeding time (BT). Since desmopressin (DDAVP) is able to achieve both these goals in the majority of patients, it is the treatment of choice. Some patients, however, are not responsive or become refractory to DDAVP. In these, blood products maintain an important therapeutic role, and there is a need to assess the efficacy of the recently available virus-inactivated plasma concentrates, which contain both FVIII and von Willebrand factor and carry a low risk of transmitting blood-borne viruses. Our survey of the data reported in the literature indicates that all available concentrates are similarly effective in attaining high and sustained levels of FVIII after infusion. Although they often shorten or normalize the prolonged BT, that effect is less uniform. Since concentrates appear efficacious in the majority of clinical situations that require the use of blood products, they should be preferred, because of their greater safety, to cryoprecipitate produced by blood banks, which cannot be virus inactivated. PMID- 1642003 TI - Anti-IgG autoantibodies in HIV-infected hemophilia patients. AB - Sera of 76 HIV-negative hemophilia patients, 103 HIV-positive (HIV+) hemophilia patients free of AIDS or AIDS related complex (ARC), and 32 HIV+ hemophilia patients with AIDS/ARC were tested for four different anti-IgG activities. IgG anti-F(ab')2 gamma, IgM-anti-F(ab')2 gamma, and IgG-anti-Fc gamma serum activities were significantly associated with the clinical stage of HIV infection, whereas IgM-anti-Fc gamma was not. IgG-anti-F(ab')2 gamma activity was found to be caused by cross-reaction of anti-HIV antibody with an epitope within the constant CH1 domain of human IgG. HIV+ hemophilia patients with severe thrombocytopenia (less than 50,000/microliters platelet counts) had significantly higher IgM-anti-IgG activity than patients with greater than 50,000/microliters platelets. Because anti-IgG antibodies possess immunoregulatory properties, our results may serve as a possible explanation for the frequent B cell disorders encountered in HIV-infected patients. PMID- 1642004 TI - Leukocyte depletion of red cell concentrates by filtration: influence of blood product temperature. PMID- 1642005 TI - HIV-2 infection in high-risk individuals with indeterminate HIV-1 western blot analysis: a serologic surveillance. PMID- 1642006 TI - Note on the measurement of alanine aminotransferase in the screening of blood donors. PMID- 1642007 TI - Disasters in health. Typhoid epidemic in Jamaica, 1990. PMID- 1642008 TI - [Brief definitions of medical ethics concepts. 20. Potentiality]. PMID- 1642009 TI - [Psychotherapy in advanced age]. AB - The ageing patient, especially in rehabilitation, faces an unknown and sometimes critical situation, in which he is as much in need of psychotherapy as he can benefit by it. Combinations of hypnoid techniques together with group interactions and analytically orientated verbal therapy have proved to be most suitable, bringing into action the somatotropic as well as the psychotropic effects of psychotherapy. Pleasure-orientation, variety and imagination as psychotherapeutic dimensions have to be integrated into rehabilitation, which otherwise would remain incomplete patchwork. We need a renaissance of general communicative culture in the first place, additionally specific verbal techniques for special (critical) situations, e.g. when talking to the incurably diseased, to his family, etc. Psychotherapeutic reasoning and acting must become part of the training and a permanent concomitant factor in all health professions. The same must hold good for public life, politics and society, if we strive for generally effective achievements for the ever-increasing number of elderly patients. It opens vast new fields of action for a new generation of psychotherapists who will be prepared to shed antiquated prejudiced stereotypes. PMID- 1642010 TI - [Concomitant depression and its treatment]. AB - Accompanying depression is especially common in elderly, chronically ill patients and rehabilitation patients, where a physical illness and/or disablement is accompanied by depression. Treatment should always be focussed in a "polypragmatic" manner on both physical or psychic symptoms. In particular psychotherapy (see article by Barolin), pharmacotherapy (referred to in this article) and physiotherapy (described further in other literature) are of importance here. Advantage is to be taken of the polar dimensions of different types of antidepressant drugs, namely the increase in drive or sedating effects. However, the increased rate of side effects from some drugs among elderly patients is not to be ignored. Taking the above into consideration, the new antidepressant, Fluctine (Fluoxetine), has proved to be effective among our randomly selected patients. This is on account of its relatively fast onset of action, minimal side effects and its slight increase in drive. The group of non responders (one third of the patients) showed no decrease in depressive symptoms when other antidepressants were substituted. As expected those patients suffering organic-brain illness responded worse and represent a large percentage of the non responders. These data prove the results of previous findings that patients with organic-brain illness generally respond worse to antidepressant medication. Thus Fluctine can be recommended for elderly patients with accompanying depression. PMID- 1642011 TI - [Abortion from the Catholic perspective]. AB - The embryo possesses the right to life. Therefore abortion is an forbidden act of killing. There is no sufficient reason to justify it. Especially the burden of pregnancy in situations of social conflicts and change of carriere-plans cannot justify abortion. Also there can be no demand of conscience to legitimate an abortion. The Catholic Church itself offers support for women in conflict situations. The Church condemns abortion, not the person, who needs a special attention in such a situation. PMID- 1642012 TI - [Abortion: interviews and discussions]. AB - The paper focuses on the high number of annual induced abortions and is discussing alternative ways to cope with this problem. 151 women were interviewed on the day of abortion. 39 women were interviewed with more detail on the psychological consequences of their abortion carried out 7 to 8 years ago. Main topics of the questionnaire in the first group concerned on the background of conflicts arising from pregnancy, on the information provided by physicians and social advisory boards, and on the question under what circumstances abortion could have been avoided. In the second group 50% of the individuals carried out multiple abortions (up to 5 times). In the conversations it was tried to get more detailed informations on the present well-being, on severe life-events which had taken place in the past years history and on the present point of view to the abortion in 1981. PMID- 1642013 TI - [Theses on the ethics and legal ethics of abortion]. AB - The author subjects the principal ethical and pragmatic arguments for the moral and legal rejection of abortion to critical scrutiny. He concludes that a prohibition of abortion can be justified neither by considerations of individual and social consequences nor by the standard arguments intended to show that abortion is intrinsically wrong as a form of killing specifically human life. PMID- 1642014 TI - Recent advances in medically assisted conception. Report of a WHO Scientific Group. PMID- 1642015 TI - [Asbestos and tumors]. PMID- 1642016 TI - [Epidemiology and clinical aspects of pancreatic cancer]. PMID- 1642017 TI - [Endocrine-active pancreatic tumors]. PMID- 1642018 TI - [Some new aspects of vaginal candidosis in the female]. PMID- 1642019 TI - [Myopathy with carnitine deficiency and lactic acidosis. A contribution to differential diagnosis of carnitine deficiency myopathies and mitochondrial myopathies]. PMID- 1642020 TI - [Ludwig Aschoff (10 January 1866 to 24 June 1942)]. PMID- 1642021 TI - [Chemical structure, biotechnical production and clinical use of recombinant erythropoietin]. AB - The renal glycoprotein hormone erythropoietin is an essential growth factor for the erythrocytic progenitors in the bone marrow. Erythropoietin deficiency is the main cause of the anemia in chronic renal failure. Genetical engineering has made it possible to produce recombinant human erythropoietin (rhu-Epo) in CHO cell cultures as a pharmaceutical compound. Endogenous and recombinant erythropoietin are similar with respect to their biological and chemical properties (M(r) 30,400 Da, protein content 60%, 165 amino acids, 4 carbohydrate side chains). With few side-effects, rhu-Epo corrects the anemia of predialysis and dialysis renal failure patients. In addition, rhu-Epo treatment may reduce the need for blood transfusion in other types of anemias, including those of rheumatoid arthritis, AIDS, malignant diseases and major surgical procedures. However, rhu-Epo has not been approved as yet for treatment of non-renal anemias in Germany. PMID- 1642022 TI - [Anti-oxidative therapy of pancreatitis--an 18-month interim evaluation]. AB - 99 patients affected with acute pancreatitis of different genesis were treated in hospital (necrotizing n = 38, mild form n = 61) from May 1990 to November 1991. Nearly 80% of these illnesses were ethanol-induced, 12% were of biliary origin. 90 patients were submitted to an adjuvant antioxidant therapy with selenium and D alpha-tocopherol (necrotizing form n = 29, mild form n = 61). The average lethality rate of 34% (1982-1989) fell to 1.1% (1 female patient with biliarily induced pancreatitis). No lethal courses were observed in alcohol-induced, idiopathic, post-traumatic, and post-operative forms. Clinical courses proceeded more easily under adjuvant antioxidant therapy, surgical treatment was not necessary. A treatment at reasonable costs can be made in all general internal wards. PMID- 1642023 TI - [Coronary heart disease and insulin concentration in type II diabetic patients- results of a diabetes intervention study]. AB - There is experimental, clinical and epidemiological evidence that elevated insulin levels are associated with development of atherosclerosis. Early results came from studies in non-diabetics, but the situation with respect to diabetes is more complex and not so clear. The Diabetes Intervention Study is a population based follow-up study in newly detected type II diabetics (30- to 55-yr-old). After 5 years 431 men and 320 women received a complex check up with oral glucose tolerance tests and measurements of plasma insulin and glucose levels, fasting and 2h post-load. Regarding the metabolic parameters, the fasting and postprandial insulin levels were higher among the patients having coronary heart disease (15% of men, 36% of women), as compared to patients without this disease. In multivariate analysis sex, age, antihypertensive treatment, blood pressure, body mass index, and fasting insulin levels were independently associated with the prevalence of coronary heart disease in patients with non-insulin dependent diabetes mellitus (NIDDM) treated with diet and/or oral antidiabetics. Body mass index and triglycerides were the only variables that independently correlated to insulin: fasting insulin = 0.4 (body mass index) + 0.1 (triglycerides) - 4,2. In future prospective studies of diabetics relating insulin concentrations to the development of vascular disease are of particular interest and necessity. Because hyperinsulinemia may contribute to accelerated atherosclerosis in NIDDM-patients, the aim of the treatment of type II-diabetes should be to correct hyperglycemia without aggravating insulin levels and other cardiovascular risk factors. PMID- 1642024 TI - [Do piroxicam and diclofenac impair reaction performance?]. AB - The non-steroid agents diclofenac (1 mg/kg) and piroxicam (0.3 mg/kg) were studied for their performance-influencing effect in an acute placebo controlled cross-over trial involving 11 normal subjects in intraindividual comparison. Various cognitive tests (vigilance measurement, d2-test, concentration performance test), a determination test, and a flicker frequency test did not reveal verum effects when compared to placebo. In contrast, for subjects administered piroxicam, the self-state questionnaire according to Nitsch showed marked positive effects on the motivation and activation on the subjects. Numerical improvements (without being statistically significant) were also seen with respect to outgoingness and exertion increase. Moreover, subjects administered piroxicam were observed to be more concentrated and relaxed, whereas diclofenac exerted no influence on performance and the state of mind. PMID- 1642025 TI - [Activated circulating lymphocytes as a parameter for clinical activity in patients with Crohn disease]. AB - Patients with Crohn's disease exhibit peripheral lymphocytes during exacerbation which express activation associated epitopes on their cell surface. We have therefore enumerated circulating lymphocytes in 36 patients with Crohn's disease by immunofluorescent staining using monoclonal antibodies directed against activation associated antigens (CD 25, CD 71, CD 38 and MHC-class II-antigens, respectively). We found a highly significant correlation between the percentage of activated lymphocytes and the clinical activity. Thus in our experience measuring of activated peripheral lymphocytes proved as a valuable parameter in assessing the clinical activity of Crohn's disease for a well-timed medication. PMID- 1642026 TI - [Malondialdehyde concentration in blood plasma of patients with liver diseases]. AB - Malondialdehyde (MDA) level was determined spectrophotometrically with thiobarbituric acid method on 50 healthy persons and 160 patients with alcoholic and nonalcoholic liver diseases. Alcoholics without liver damage show normal plasma MDA values. Alcoholic fatty liver, alcoholic hepatitis and alcoholic liver cirrhosis cause an increase of MDA values. The highest concentrations of MDA were found on patients with acute virus hepatitis. Also noninfectional hepatitis and nonalcoholic liver cirrhosis showed an elevated MDA-Level. Liver damage and lipid peroxidation are considered as closely connected processes. PMID- 1642027 TI - [How painful is intensive insulin therapy?]. AB - Injection-pain was assessed in 39 type-1 diabetic patients in relation to an insulin injection (with an insulin-pen) into the upper arm, the abdomen, and the thigh and in another 10 patients, pain associated with finger-pricking for blood glucose self-monitoring was assessed. Pain perception was recorded on a visual analogue scale. According to the results, injections were relatively painless with an average (median) pain-score of less than 10% of maximum pain. Injection pains varied in relation to the injection sites (upper arm greater than thigh greater than abdomen). Least painful (n = 44) versus most painful (n = 39) injections were distributed as follows: upper arm 20% vs. 46%, abdomen 43% vs. 23%, thigh 36% vs. 31% (chi 2 7.26, df2, p less than 0.05). Finger-pricking was no more painful than injecting insulin. It is concluded that insulin injecting (e.g. with insulin pens) and blood glucose self-monitoring in general is not very painful. However, if this positive conclusion also applies to long-term performance of intensive insulin therapy remains to be proven. PMID- 1642028 TI - [Appointment modalities in the history of the medical faculty of the Halle University. I. The 18th century]. AB - Modalities of appointment to medical professorships and readerships were quite differently managed in the period of the first century of Halle University opened in 1694. The appointments of the initial era secured a top position to Halle University (Faculty of Medicine). Then followed decades of decline which not at last resulted from a personal policy being not clear-sighted enough. Nearly from about 1780 new conceptions in the modalities of appointment referred to the bloom of the decades of foundation. PMID- 1642029 TI - [Occupational rights in medical practice. II]. PMID- 1642030 TI - [Pollex flexus congenitus]. AB - The authors report on the incidence, clinical picture, etiology, pathogenesis and treatment of congenital pollex flexus, and communicate the results of surgery on 52 thumbs. The permanent flexion anomaly in the interphalangeal joint and a hard, palpable knot in the long flexor tendon of the thumb over the metacarpophalangeal joint are typical for the deformity. Although these changes are sometimes observed immediately post partum, delayed diagnosis and treatment are more common. The hypothesis that it is a hereditary, endogenous condition is supported by observations in twins, relatively frequent bilateral occurrence and a high familial incidence. Constriction of the synovial sheath over the basal joint of the thumb is a key pathogenetic factor, although little is known about its causes; anatomical factors, influences affecting the growth of the sesamoid bones, and mechanical causes have been postulated. A more plausible hypothesis was first advanced by Jeannin. Like Hueston and Wilson 100 years later, he compared the tendon to a thick thread which had to be passed through a narrow eye of a needle: as a result, the "thread" would be frayed and compressed. The knot in the tendon is held to be a secondary phenomenon. The pathologicoanatomical picture varies. Lymphocyte and monocyte infiltration, and metaplasias to fiber cartilage have been detected in specimens excised from the tendon and the synovial sheath. However, pathologic changes have not been found in all cases. In the first year of life conservative therapy may be attempted, with temporary splinting of the thumb following manual correction of the flexion anomaly in the interphalangeal joint.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642031 TI - [Indications and technique of partial arthrodesis of the carpus]. AB - Partial arthrodesis of the carpus has again become a topical method. The technique has been improved and the range of indications has been extended. Fusion of certain areas has indeed been propagated as first-line therapy, for example in lunatum necrosis or as an important additional operation in substitution plastic surgery. Partial arthrodesis of the carpus is intended to eliminate mechanisms which has become pathological whilst preserving the best possible mobility. Partial arthrodesis alters the movement pattern of the individual ossae carpi. Moreover, the pressure in the adjacent joints also rises. The risk of a new pathological process is considerable. Recent publications report on a rapid development of impingement and symptoms. The most frequent partial arthrodeses are discussed. The indications and the direct consequences are critically analysed and explained with reference to examples. Technical details and potential dangers are described. An STT-arthrodesis is indicated for osteoarthritis of these bones. The radio-lunar arthrodesis is recommended for ulnar drifting of the carpus in cases of rheumatoid arthritis. Reconstruction of the central axis with arthrodesis of the capitate-lunate is indicated for pseudarthrosis of the scaphoid with carpal collapse. Other combinations are possible, they cause however greater functional deficits. We recommend a critical analysis of the function of the entire carpus before the operation. Caution is called for when an incipient arthrosis is present in the adjacent joint. Partial arthrodesis of the carpus is rather a temporary solution, since it enables time to be gained. Total arthrodesis is the ultimate resort. PMID- 1642032 TI - [Results of resection of the head of the ulna]. AB - A follow up of 57 wrists with resection of caput ulnae shows different value to different groups of patients. The painful arthrosis of distal radioulnar joint gives indication in posttraumatic cases. Release of pain and improvement of range of motion will be achieved; loss of strength is the most impairing problem for younger patients. 13 patients out of 21 with posttraumatic deformities were satisfied with the post-operative outcome; 13 patients showed significant loss of strength, too. In case of rheumatoid arthritis with caput-ulnae-syndrome the resection is without alternative, needs to be combined with the arthrodesis of radiolunar-joint, if necessary. 20 of 34 rheumatics were satisfied with the outcome after resection of caput ulnae; in 6 cases an ulnar drift was evident, which implied simultaneous or later partial arthrodesis of the wrist. For all patients release of pain decided on their satisfaction with surgery. PMID- 1642033 TI - [Arthroscopy and MRT of the shoulder--a comparative retrospective analysis]. AB - MR Imaging is proving to an effective means for evaluating the shoulder. The use of a surface coil and high resolution scanning techniques have allowed detailed analysis of normal anatomy and suspected pathology of the shoulder. On the other way arthroscopic inspection provides a more extensive visualization of the joint in different positions. 31 patients, well documented, were studied with MR Imaging and correlated with findings in arthroscopy and open revision in some cases. The MR studies were retrospective interpreted without the knowledge of the results of other diagnostic procedures. For the evaluation of rotator cuff tears MRI proved to have a sensitivity of 83.3% and an accuracy of 90.3%. When Arthroscopy was correlated with open revision the sensitivity was 61.8% and the accuracy 78%. Labral pathology and Hill-Sachs lesions will be better evaluated in arthroscopy as in MRI (sensitivity of arthroscopy 100% and of MRI 69%, accuracy of arthroscopy 100% and of MRI 87.1%). With the high resolution scanning technique and a surface coil MRI has been shown to be useful in the evaluation of rotator cuff tears and impingement syndrome but not in diagnosis of labral pathology and Hill-Sachs lesions. PMID- 1642034 TI - [Clavicula pro humero--a new surgical method for malignant tumors of the proximal humerus]. AB - In the majority of cases with malignant tumors in the proximal part of the humerus a limb saving tumor resection is possible. Reconstruction of the defect is necessary to maintain the length of the arm and to create a fulcrum for elbow flexion and extension. Several methods of reconstruction have been described in the literature including the fixation of distal humerus to the second rib or to the clavicle by means of Kuntscher-nails, the implantation of a proximal humerus prosthesis without or with accompanying bone transplantation, a bridging of the defect using an allograft or an arthrodesis of the shoulder joint using free or vascularized bone transplants. The following paper describes a new surgical procedure whereby the vascularization of the clavicle is preserved and the clavicle used to bridge the defect. Although the follow-up period of the patients operated on so far in this way is relatively short, the functional advantages of this operation over the other forms of reconstruction can already be observed. PMID- 1642035 TI - [Surgical therapy of metastases of the pelvis and sacrum]. AB - We are reporting on 42 surgical and 5 conservative treatment approaches in metastases of the pelvis and sacrum. With an average disease-free survival of 14.4 months the majority of the lesions were resected intralesionally. In the area of the ischium and the pubis resection alone was done without further stabilizing measures. If the resection was in the area of the iliac wings, stabilization was achieved by means of osteosynthesis in 50% of the cases. Periacetabular resections required reconstruction with endoprotheses in all cases. In patients with good prognosis and solitary metastases also extralesional resections were performed. Reoperated embolization was used in advanced stages of the disease or if the metastases were not easily accessible surgically. Because of the complexity of pelvic resections and the often considerable loss of function, patients with metastases are often treated with intralesional resection and osteosynthesis. In exceptional cases, if radiotherapy had failed or multiple intralesional resections were followed by recurrences, we feel however that extralesional resection should be attempted with good prognosis for the patient. PMID- 1642036 TI - [Results of surgical therapy of knee flexion contractures in patients with myelomeningocele]. AB - This study reports the results of 98 operations for correcting knee-flexion contractures, which were performed between 1972 and 1989 in 60 patients with myelomeningocele. 13 knees had hamstring lengthening and 85 knees had radical flexor release. In 4 patients, who had flexion-contractures of more than 50 degrees, the soft tissue release was combined with supracondylar extension osteotomy. 58 patients had additional hip-flexion-contractures and 39 patients had feet deformities. The average age at time of surgery was 8 years, 3 months. The average follow-up-period was 65 months with a minimum of 1 year and a maximum of 13 years. In 92 knees a permanent extension ability could be achieved. In 6 knees a recurrence of flexion-contracture occurred making a second surgery necessary. The main problem in the postoperative period were 13 skin necroses, which were seen mainly after an s-shaped incision. As a conclusion a perpendicular midline incision is recommended. After surgery 11 patients could be provided for the first time with an orthoses. In the remaining the upright body position or the erection of the orthoses could be improved. PMID- 1642037 TI - [Effect of constitutional ligament laxity and physical stress on development of patellar tip syndrome]. AB - Studies were performed in order to obtain information on the pathogenesis of patellar tip syndrome (PTS). Using a finger hyperextensiometer, ligamental laxity tests were performed on athletes, non-athletes and controls. Ninety-eight PTS patients who did not indulge regularly in sports, 39 patients from the German federal volleyball league, and 400 healthy controls were examined. No difference in the extensibility of ligaments was found between the patients from the group of competitive athletes and the controls. However, a significantly increased extensibility of the finger joints was found in all age and sex groups with "spontaneous" PTS. The authors conclude that 1) constitutional laxity of the ligaments is a key predisposing factor for PTS, and 2) PTS is triggered by physical stress. Susceptibility to microtrauma at the insertion of the patellar ligament is a function of the constitutional strength of the ligaments. PMID- 1642038 TI - [Results of isolated lateral retinaculum release as a treatment method in patello femoral dysfunction]. AB - The results of lateral retinaculum-release by arthroscopic, subcutaneous and open technique on 122 patients are presented. Within a follow-up period of 3.68 years in average the postoperative success rate was 56%. The results of surgery if the cartilage of the patella was unchanged--as well as with isolated medial or lateral chondromalacia--were good. If there was medial and lateral chondromalacia the isolated retinaculum-release is insufficient. The rate of postoperative complications (effusion, haemorrhage) by arthroscopic surgery technique is with 11.1% distinctly above the results by the subcutaneous technique, which amounts to a mere 3%. The 30 degrees degree-tangential x-ray technique combined with external rotation of the lower leg and simultaneous tension of the quadriceps gives much better information of the position of the patella than the 30 degrees degree x-ray without quadriceps tension. PMID- 1642039 TI - [Comments on the use of the "life-table method" in orthopedics]. AB - In the description of long term results, e.g. of joint replacements, survivorship analysis is used increasingly in orthopaedic surgery. The survivorship analysis is more useful to describe the frequency of failure rather than global statements in percentage. The relative probability of failure for fixed intervals is drawn from the number of controlled patients and the frequency of failure. The complementary probabilities of success are linked in their temporal sequence thus representing the probability of survival at a fixed endpoint. Necessary condition for the use of this procedure is the exact definition of moment and manner of failure. It is described how to establish survivorship tables. PMID- 1642040 TI - [Effect of surgical draping on bacterial contamination in the surgical field]. AB - Standardized samples were taken from the skin of 100 patients immediately before and after their hip operation. 50 patients were operated with and 50 patients without use of plastic drapes. The samples were evaluated quantitatively and qualitatively by the employment of usual microbiological methods. The statistical analysis revealed that at the end of the operations there were a) as many microbes on the drape as on the skin where no drape had been used and b) many more microbes under the drapes than either on them or on undraped skin. The value of the plastic drape as a means of preventing infections has to be doubted. Discontinuing the use of plastic drapes seems to be justified. PMID- 1642041 TI - [Effect of shock waves on the strength of connection between bone and polymethylmethacrylate. An in vitro study of human femur segments]. AB - The increasing number of revision surgery for failed total arthroplasty including the most difficult aspects of cement removal has lead to various developments of new instruments and techniques to facilitate this procedure. In this in vitro study the effect of extracorporeal shockwaves on the bone-cement interface under this view was investigated. At first the pressure reduction of bounding shockwaves in their progress through compounds consisting of cortical bone-PMMA and cancellous bone-PMMA by means of a needle pressure probe was measured. In the second part of the experiments the mechanical and morphological effects of ESW on the PMMA-Bone-Interface of human femoral segments was tested. Using bone cement cadaveric femoral segments were implanted with stainless steel rods within the medullary canal and the PMMA-Bone-interface was treated with ESW. After treatment the segments were examined mechanically, radiologically and by microscopy. Between the treated and the control group no difference was found which could give any a reference to the disruption of the Cement-Bone-Interface caused by ESW. However, there were observations which indicated that ESW induces a increasing risk of intravasation of bone marrow. Considering these facts ESW seems not to be a good clinical adjunct in revision surgery. PMID- 1642042 TI - [Induction of sarcoma by resorbable osteosynthesis material in the rat. A preliminary report]. AB - In an experiment testing the resorption of Poly-l-lactate in the back muscles of Cara rats a foreign body sarcoma occurred in two rats. 20 months after implantation of a body of high molecular weight poly-l-lactate a malignant fibrous histiocytoma developed in one rat. A soft tissue tumor, which was classified according to the immune-histiochemical analysis as a neurogenic sarcoma, developed 23 months after the implantation of a body of injection-casted poly-l-lactate of high molecular weight in a second rat. PMID- 1642043 TI - [Case report of transcondylar stress fracture of the distal femur in the elderly]. AB - We report the case of a 67-year-old woman with a transcondylar stress fracture of the femur. Problems in diagnosis and treatment of elderly patients with stress fractures around the knee joint are illustrated. PMID- 1642044 TI - [Comments on the contribution: F. Grill and B. Frischhut: "Results of treatment of chronic congenital hip dislocation after learning to walk]. PMID- 1642045 TI - [Surgical indications and technique of persistent and recurrent spontaneous pneumothorax]. AB - The thoracotomy is the most invasive and most effective method for treatment of spontaneous pneumothorax. This method is indicated not only for recurrent pneumothoraces but also if conservative treatment does not induce expansion of lung. The primary operation is indicated absolutely in only some cases (spontaneous hemopneumothorax, pneumothorax in pregnancy). Today it is possible to operate for relative indications: Surgery has a small rate of complications, mortality and relapse (below 1%). The operation removes the causes of pneumothorax and protect for relapse of the pneumothorax via pleurodesis with mechanical irritation of the pleural surface. PMID- 1642046 TI - [Symptom: spontaneous pneumothorax. Indications for drainage therapy?]. AB - Spontaneous pneumothoraces follow lesions of pleuropulmonary tissues. Improvements of diagnostical and therapeutical management seem to change the traditional way by using thoracic drainage-systems. What value does drainage therapy still have? PMID- 1642047 TI - [Thoracoscopic pleurodesis in persistent and recurrent pneumothorax]. AB - 103 patients with recurrent or persistent pneumothorax have been treated with local application of fibrin and talcum by a thoracoscopic procedure. The method was successful in 97 patients (94.2%) and lead to a stable and complete reexpansion of the lung within 6.3 days. As a direct consequence of the procedure itself only a few and minor complications occurred during a mean hospitalization time of 10.4 days. The longterm followup over a mean period of 6.4 years revealed a recurrence rate of 15%, although half of the episodes occurred early during the first three months. After 6 years, 80% of the patients were completely asymptomatic and spirometric lung function was restored to normal values. We therefore consider thoracoscopic pleurodesis to be a successful and safe method for treating complicated pneumothorax. PMID- 1642049 TI - [The treatment concept of chylothorax including surgical procedures using fibrin glue]. PMID- 1642048 TI - [Thoracoscopic treatment of spontaneous pneumothorax using fibrin pleurodesis]. AB - In 33 patients with a recurrent spontaneous pneumothorax, a thoracoscopic pleurodesis with fibrin glue was performed under local anesthesia. During an average postoperative observation period of 4 years the relapse frequency was 39% (13 cases). In these cases thoracotomy was performed and a new relapse of pneumothorax occurred in 3 patients (23%): Application of thoracoscopy with fibrin glue pleurodesis should only be applied in those patients without large emphysema vesicles and without large coalescences. Under these conditions the relapse frequency could be reduced to 26%. The thoracoscopic treatment of recurrent pneumothorax by using fibrin glue and local anesthesia in well selected patients is an alternative procedure to thoracotomy. PMID- 1642050 TI - [Morphology and therapy of tracheal cysts]. AB - Following a short representation of etiology, morphology and classification of cysts of trachea the symptoms, diagnosis and therapy were described. 7 cases of the own patients material in 27 years are presented extensively. PMID- 1642051 TI - [Experiences with surgical therapy of Budd-Chiari syndrome]. AB - The obstruction of the hepatic venous outflow tract with or without involvement of the inferior vena cava results in the Budd-Chiari syndrome (BCS). With its very heterogenous etiology and variable epidemiology the rare disease either takes a chronic or an acute foudroyant clinical course. In general the prognosis is poor. Together with the clinical signs the diagnosis is based on radiological measures and the histology of the hepatic parenchyma. The exact etiological investigation of the BCS is of great significance. Typical findings are discussed and a diagnostic scheme is developed. Between 1979 and 1991, altogether 16 operations were carried out in 13 patients with a BCS. Predominantly there were undertaken a porto-systemic shunt procedure or an orthotopic liver transplantation, respectively, in 6 cases each. The need for an always individually tailored therapeutic strategy of the BCS is underlined by a case history. An overview analyzes the different therapeutic modalities of the BCS and their differential indications. PMID- 1642052 TI - [Isolated pulmonary coin lesion as an indication of Wegener's granulomatosis]. PMID- 1642053 TI - [Left-sided diaphragmatic rupture with intrathoracic migration of the ruptured spleen. A rare cause of hemothorax]. PMID- 1642054 TI - [Our surgical heritage. On the history of clinical liver transplantation in Germany]. PMID- 1642055 TI - [Ultrasound biometry of the fetal heart]. AB - We report on biometric measurements of the fetal heart with the TM-technique; these measurements were carried out between the 20th and 40th gestational week. The right and left endsystolic atrial and ventricular diameters were, measured, as well as the diameters of the large vessels, i.e. aorta and pulmonary artery; finally, the septal thickness was determined. Our measurements show a linear progression of the diameters in question, the right-left ratio of the atria and ventricles was close to one, so was the ratio between aorta and pulmonary artery. Our results are compared, as far as possible, to the literature. PMID- 1642056 TI - [Ovarian stimulation with clomiphene is not a risk factor for extrauterine pregnancy]. AB - In a retrospective cohort study of 252 patients with ectopic pregnancies the possible association between use of clomiphene citrate and the occurrence of an ectopic pregnancy was examined. Seventeen out of 252 patients had been treated with clomiphene. Epidemiologic data and animal experiments suggest, that there may be a role of clomiphene in the etiology of ectopic pregnancy. Marchbanks et al. [6] reported that patients who used clomiphene were found to have a relative risk of 10.0 for ectopic pregnancy. The analysis of our own data show an accumulation of classic risk factors as history of pelvic inflammatory disease or of microsurgery for treatment of tubal disease in the clomiphene group. The higher rate of ectopic pregnancies in patients who have been treated with clomiphene is more likely associated with the diagnosis of infertility than with the use of ovulatory-inducing agents. Clomiphene treatment is no independent risk factor in the etiology of ectopic pregnancy. PMID- 1642057 TI - New criterion of placental barrier maturity. AB - In 120 full term pregnancies and 20 premature deliveries number of plates thickness of epithelial plate and number of vili in 1 mm2 placenta have been determined by histological investigation. These morphometric studies lead to the following conclusion: the increase of placental transport ability corresponds with fetal age and weight. The ratio between number of plates to their thickness is introduced as transportation index. There is a correlation between placental morphology and fetal maturity. PMID- 1642058 TI - [The antibacterial effectiveness of hexetidine vaginal tablets on pathogen flora of the cervix and vagina]. PMID- 1642059 TI - [Disinfection in gynecologic practice]. AB - It will be pointed to the necessity of the demand according to a standardize sanitary regime which concerns ambulant practicing gynaecologists. A sanitary pattern scheme is introduced. PMID- 1642060 TI - [Clinical use of photodynamic therapy in gynecologic tumor patients--antibody targeted photodynamic laser therapy as a new oncologic treatment procedure]. AB - The clinical report addresses the first application of a antibody-targeted photodynamic laser therapy with Phthalocyanines. Photodynamic therapy (PDT) has been proposed as a further treatment modality in oncology. The concept of PDT is based on the interaction between a dye which is accumulated in the target and laserlight. The phototoxic effect is achieved by the augmentation of oxygen radicals. The improvement of the selectivity and the reduction of side-effects is achieved by our concept of using an antibody-targeted phthalocyane induced PDT. The clinical application of the antibody-targeted Phthalocyanine was performed in 3 patients suffering from an advanced ovarian carcinoma (FIGO III). By means of an ultramicroscopical analysis a selective devitalisation of tumor cells was demonstrated. The perspective of PDT reaches far beyond the application for the ovarian carcinomas and relates to all tumor types, where the presence of tumor associated antigens implicates a treatment in a similar way. PMID- 1642061 TI - [Compliance in gynecologic screening and causes for delayed tumor diagnosis in East Thuringen]. AB - The public health service of the former GDR paid special attention to early recognition and the registration of malignancies. Due to this efforts the staging of cervical cancer moved to more low-staged tumours admitted to our hospital from the eastthuringian region. In spite of this around 35% of our patients with malignant diseases had stage II or higher staged tumours ad admission. The causes for delayed perception were analysed. Campaign-like preventive actions formerly supported by factories and public health service will not take place again. The responsibility for secondary prevention has to be taken over by practicing gynaecologist in cooperation with the general practitioner. A pilot study revealed that only 11% of the women followed a written invitation for a preventive gynaecological examination. But a general practitioner concerning the patients individuality persuaded 75% of his patients letting perform such a check up. The family doctors direct advice to consult a gynaecologist is the most effective way to get the patients compliance for a preventive examination. The epidemiology and results of therapy will become evident by duty of notification and central registration of malignancies. Relatively centralized therapy and obligatory follow up under the responsibility of the treatment center for about five years enhance the therapeutic results. The positive experience of gynaecological oncology of the eastern part of the Federal Republic of Germany ought to be maintained and should be developed. PMID- 1642062 TI - [A case of full term ovarian pregnancy]. AB - A term ovarian pregnancy with a stillborn infant, weighting 3,100 g is reported. The authors believe, that in case of an advanced ectopic pregnancy only the extrauterine, but not the precise origin could be diagnosed ultrasonographi-caly. PMID- 1642063 TI - [Malignant teratoma of the ovary in childhood and adolescence--a case report]. AB - This is a report on a 15 year old patient with malignant teratoma grade III of the right ovary in stage Ia (FIGO). The adequate treatment of this rare tumors which occurs preponderant in children and adolescents supposes an accurate and thorough histologic analysis. Our patient was treated initially by unilateral oophorectomy followed by an polychemotherapy with Vincristine, Actinomycin D and Cyclophosphamide. Regular monitoring of the tumor markers AFP and beta-HCG before and after surgery is indispensable to control the development. PMID- 1642064 TI - [Our gynecologic history. Karl Schuchardt on the 90th anniversary of his death]. AB - The surgeon Karl Schuchardt dedicated most of his life to the surgical treatment of cervical carcinoma. He improved the surgical access by enlarging the introitus with a particular perineotomy bearing his name today. Dr. Schuchard died ninety years ago in Stettin. PMID- 1642065 TI - Effect of operation theatre environment on laparotomy wound infection in bovines. AB - Right flank laparotomies were performed on five clinically healthy cross-bred calves. A significant (P less than 0.05) increase of 22.1 and 2.7 times in bacterial count in subcutaneous tissue and incised skin edges, respectively, and a non-significant increase (1.1 times) in muscles and peritoneum had occurred during 15 minutes exposure to the operation theatre environment. Poly morphonuclear cells and Gram-positive and Gram-negative bacterial infiltration was also demonstrated histopathologically in muscles and peritoneum. Organisms isolated from operation theatre air were Staphylococcus aureus, other Staphylococcus spp., Bacillus spp., Micrococcus spp., and yeast. Usually similar organisms were also found on the laparotomy wound, just before closure of abdomen. Operation theatre environment is concluded to be a significant source of operative wound contamination. Provision of separate operation theatres for different types of surgery in different species is recommended and the necessity for their regular disinfection is stressed. PMID- 1642066 TI - Electron microscopy of the endometrium of camels in normal and some diseased conditions. AB - Ultrastructure of the camel's endometrium in normal and diseased conditions, was studied using the electron microscope. The samples were obtained from 6 normal uteri and 10 uteri with inflammatory lesions. Three ovaries of the latter 10 uteri showed ovarian cysts. All the animals were non-pregnant. No cyclic changes were taken in consideration because the camel is an induced ovulator animal. The surface and the glandular epithelium of the normal uteri consisted of one layer of tall columnar cells, resting on an undulating membrane. The free borders of cells showed microvilli, motile cilia and zeiotic blebs. Desmosomes and gap junctions were seen as means of connections between the neighboring cells. The nuclei were large, oval and situated in the lower half of the cells. Two types of mitochondria were seen. One type was small, rounded and dilated, and the other was large and elongated. Many lipid droplets and scanty glycogen granules were common findings in the normal cells. Granulated bodies similar to those described in the epithelium of the human uterus and containing acid phosphatase were found. Many other cytoplasmic organelles and granules were seen. The endometrial stroma consisted mainly of stromal cells of irregular shape, and collagen fibres. The collagen fibres were present in amounts larger than many other species. In the diseased uteri, the changes in the epithelium consisted mainly of hyperplasia of the cells and marked increase of all cytoplasmic inclusions and vacuoles. There was also marked increase in the number of the crossing lymphocytes through the epithelial layer. The collagen fibres of the stroma increased in amount and the stromal cells became similar in shape to the fibroblasts. A large number of mast cells as well as other types of inflammatory cells infiltrated the stroma. Non specific bacterial infections were detected on bacteriological examination of the inflamed uteri. Neither bacteria nor other microbial agents could be seen ultrastructurally. In an uterus associated with ovarian cysts, the microvilli of its epithelium showed marked changes in their shape and length. PMID- 1642067 TI - Teat reactions in cows associated with machine milking. AB - In the present investigations, referring to conventional milking machines and conventional milking technique, teat ends were transversally compressed for a short moment by means of a cutimeter before, during and after milking (main series), or before and after milking (additional series). The thickness of the teat ends between the jaw plates of the instrument decreased during the high flow rate phase, increased during the low flow-rate and overmilking phases, and started decreasing as soon as milking was finished. The decreased values in the beginning of the milking process reflect the thinning of the teat wall following the vacuum-induced teat elongation that occurs when the teat cups are attached. The subsequent increased values are due to active, i.e., functionally significant hyperaemia in the teat wall, especially in the specific teat venous system, and locally elevated vascular pressure. Both the thinning and the thickening seem to occur within physiologically tolerable limits. The diagnosis, proposed in the literature, of teat congestion (passive hyperaemia) and/or oedema involving risks of impaired teat and udder health has no support in our investigations. PMID- 1642068 TI - [Histological studies of a tongue-shaped formation at the intertubercular groove in the shoulder joint of the dog]. AB - Radiologically apparent unilateral changes at the intertubercular groove of the humerus were investigated histologically in three dogs and compared with the findings in an unaltered shoulder joint of a dog. Polymethylmethacrylate embedded, undecalcified sections were cut through the sulcus area at the head of humerus and through the biceps tendon, its synovial sheet and the transverse ligament, and were evaluated by light microscopy. While the tendon and soft tissue features were for the most part typical for a normal "gliding" tendon, the respective groove exhibited an again groove-like, 10-12 mm wide and up to 2 mm high exostosis consisting mainly of lamellar bone, filled with hemopoietic and fatty marrow. The normal fibrocartilaginous lining of the groove showed degenerative arthrotic changes in the altered grooves, pointing to mechanical overloading. The possible mechanisms of these ossifications are discussed. PMID- 1642069 TI - Inhibition of food intake and reticulo-rumen motility of sheep by the alpha-2 adrenoreceptor agonist clonidine. AB - The investigation of the effect of intravenous clonidine, an alpha-2 adrenoreceptor agonist, was carried out in sheep with recording of forestomach motility for 3 h and intake of chopped hay for 8 h after drug administration. Motility and food intake were inhibited by clonidine at 2 micrograms.kg-1 and at 5 micrograms.kg-1. The effects of the lower dose were prevented by idazoxan, an alpha-2 antagonist, at 0.1 mg.kg-1 but not by prazosin, an alpha-1 antagonist, at 0.1 mg.kg-1. Minor effects of the antagonists alone were noted. Blood glucose concentration was measured in all the experiments and the possibility discussed that changes in concentration, not absolute values, may have contributed to inhibitory effects. Vagal stimulation in anaesthetised sheep indicated that inhibition of motility was a central neural effect, not an effect on forestomach muscle. PMID- 1642070 TI - Selenium content and distribution in bovine and human milk from different regions of Poland. AB - Human milk and bulk cow's milk samples from 3 different areas of central Poland were analyzed for their Se content. Cow's milk specimens were also analyzed for Se distribution and GSH-Px activity. Mature human milk contained 34-68% more Se than bulk cow's milk obtained from analogous areas of central Poland. Comparison of literature values suggest, that human and cow's milk from vicinity of Warsaw and Piotrkow Trubunalski were Se-adequate but milk from Siedlce area was Se deficient. Glutathione peroxidase activity accounted for 25-31% of the total peroxidase activity of cow's milk. The majority of the Se was found in the whey fraction. It was suggested that the participation of the casein fraction in total milk selenium increased faster than milk Se content. Cow's milk obtained near Warsaw had a 2-times higher concentration of Se than in milk from Siedlce but the content of this microelement in the casein fraction (pellet) was 3-times higher. PMID- 1642071 TI - Avian paramyxovirus serotype 1 (Newcastle disease virus)--infections in falcons. AB - From eight falcons and one pigeon which died from NDV over a period of 15 months in Dubai, United Arab Emirates, PMV-1 viruses were isolated on quail embryo cell cultures. The identification of all 9 strains were achieved with the haemagglutination inhibition test against polyclonal chicken PMV-1 antiserum, against mouse monoclonal antibodies as well as with the immunoperoxidase test. Intracerebral pathogenicity index and intravenous pathogenicity index tests were also carried out. Although the virus isolates in this study fell into two distinct groups, the overall clinical symptoms displayed by the falcons tailed to demonstrate any trends or specificity unique to a group. The isolate obtained from a pigeon was similar to the isolates from one group of the falcons and showed no identity with the pigeon variant virus. PMID- 1642072 TI - Immunoglobulins, lysozyme and lactoferrin in the teat and udder of the dry cow during endotoxin-induced inflammation. AB - Immunoglobulins (Ig) and antibacterial proteins like lysozyme and lactoferrin are components of the humoral defence against infections. Changes in Ig, lysozyme and lactoferrin concentrations during endotoxin-induced inflammation in the test cistern and udder quarter of the dry cow were studied. Surgical closure of the passage between teat and udder cisterns enabled studies of reactions in the teat cistern without interference of the mammary gland. After endotoxin infusion, IgG1, IgG2, lysozyme, and to some extent IgM, increased in the teats and udder quarters, and were positively correlated with changes in somatic cell counts. No significant changes were observed in IgA or lactoferrin. The origin and significance of Ig, lysozyme and lactoferrin in the bovine teat and udder are discussed. Ig probably originated both from serum and from local plasma cells, while leukocytes appeared to be the source of lysozyme during inflammation. Secretory epithelium appeared to be the source of lactoferrin. Support for this theory was the almost total absence of lactoferrin in teat cistern samples. PMID- 1642073 TI - Comparison of Campylobacter carriage rates in diarrheic and healthy pet animals. AB - To explore the clinical significance of campylobacter infections for dogs and cats we compared intestinal carriage rates for Campylobacter sp. between animals with gastroenteritis and healthy controls. We cultured fecal specimens of 405 diarrheic dogs and 203 cats as well as 71 asymptomatic dogs and 35 cats using a selective medium in addition to filtration on a non-selective blood agar plate. We identified 224 campylobacter isolates using conventional phenotypic tests and DNA hybridization. There were 112 isolates, of C. upsaliensis, 43 C. jejuni and 69 other Campylobacter sp. For cats, there was no association between campylobacter carriage and disease, irrespective of the animals age. For dogs older than 12 months there was also no difference in campylobacter carriage rates between diarrheic and healthy animals. However, in younger dogs 44% of animals with diarrhea shed campylobacters in their feces, more than twice the rate in asymptomatic controls (21%), a significant difference. C. jejuni and C. upsaliensis contributed equally to this association between diarrhea and campylobacter prevalence. The parallel use of two culture methods enabled us to show that the recovery of Campylobacter sp. by filtration may be less than optimal and that filtering is probably unsuitable as a reference method for culturing C. upsaliensis. Finally we found that almost half of the campylobacter isolates from cats belong to a phenotypically homogeneous group of strains closely resembling C. upsaliensis but hybridizing only weakly with C. upsaliensis DNA. PMID- 1642074 TI - Microbiological study of foot-rot in lambs: isolation, elastolytic activity and antimicrobial susceptibility. AB - A microbiological study was made of an outbreak of foot-rot in lambs. Elastolytic activity was detected in all 10 Bacteroides nodosus strains isolated from the hooves of 9 affected animals. Among 14 other isolated strictly anaerobic microorganisms belonging to different species or genera only 4 strains showed a low degree of elastolysis. The 14 antimicrobial agents studied effectively inhibited "in vitro" growth of B. nodosus. PMID- 1642075 TI - Diagnostic value of gastrin for clinical bovine ostertagiosis. AB - Gastrin values were evaluated in 130 parasite naive calves, in 61 first season grazing calves during six field trials and in 8 experimentally infected adult immune cows. The gastrin values were linked to pepsinogen levels and daily weight gain. Also the influence of an anthelmintic treatment on pepsinogen and gastrin values was assessed during a clinical outbreak of ostertagiosis in a group of first season grazing calves. Mean gastrin levels in parasite naive calves were 106 pg/ml. Results show that a group mean of 400 pg/ml gastrin in first season grazing calves indicates a reduced daily weight gain but with no obvious clinical signs. During clinical outbreaks mean gastrin levels frequently reached 1,000 pg/ml with a severe weight loss and a mean pepsinogen level of 5,000 mU tyr. The serum gastrin concentration was strongly reduced 4 days post treatment. No gastrin response was noted following an Ostertagia challenge in adult immune cows. The value of gastrin as a diagnostic aid for ostertagiosis is discussed in relation to pepsinogen, the adult worm burden, larval inhibition and the technique involved in assessing gastrin. PMID- 1642076 TI - A spontaneous Yersinia pseudotuberculosis-infection in a monkey-colony. AB - A spontaneous Yersinia pseudotuberculosis (Y.p.) infection in one African Green Monkey (Cercopithecus aethiops), and nine Squirrel Monkeys (Saimiri sciureus), is reported. The clinical findings, laboratory results and pathological findings are presented. The digestive system was the most affected organ in the acute phase of the Y.p. infection, while in the subacute and chronic phases, the alterations of the lymphatic tissues, spleen or liver were severe. PMID- 1642077 TI - [Infections with original cowpox virus and cowpox-like agents in humans and animals: a literature review]. AB - In an evaluation of literature the biological, physical-chemical and antigenic characteristics of cowpoxviruses and cowpox-like agents are presented, the according diseases following a natural and experimental infection are described and their epizootiological and epidemiological aspects discussed. PMID- 1642078 TI - Detection of rabies antibody by ELISA and RFFIT in unvaccinated dogs and in the endangered Simien jackal (Canis simensis) of Ethiopia. AB - Varying levels of rabies antibody have been detected both by Enzyme Linked Immunosorbent Assay (ELISA) and Rapid Fluorescent Focus Inhibition Test (RFFIT) in the sera collected from wild and domestic canids in the Bale Mountains National Park (BMNP) of Southern Ethiopia. Rabies antibody was detected in 80% (8 out of 10) of domestic dog samples, 13.3% (2 out of 15) of Simien jackal samples and in one common jackal. Rabies virus was isolated from one dog in an area where contact with the Simien jackal could possibly occur. All samples examined from wild rodents as possible reservoir hosts for rabies were found negative. The presence of large proportion of susceptible Simien jackals in the population should be a cause of great concern in saving this endangered species from the ravages of rabies. PMID- 1642079 TI - C-peptide profiles in patients with non-insulin-dependent diabetes mellitus before and during insulin treatment. AB - The objective of the study was to evaluate the effect of insulin treatment on insulin secretion in patients with non-insulin-dependent diabetes mellitus (NIDDM). Ten patients with NIDDM were first investigated while still taking oral hypoglycemic agents, and then randomized to a crossover study with two eight-week periods of insulin treatment (oral treatment having been stopped) given either as mainly intermediate-acting insulin twice daily (2-dose) or as preprandial regular insulin and intermediate-acting insulin at bedtime (4-dose). In the patients treated with oral agents the 24-h C-peptide area under the curve was similar to that in the controls, but the profile was different with a rise at breakfast but with almost absent meal peaks during the rest of the day. Insulin treatment improved glycemic control markedly, lowered urinary C-peptide excretion and the serum C-peptide concentrations being reduced by more than 50%. The shape of the C peptide profiles was unaltered and there were no significant differences between the two insulin regimens. The decrease in serum C-peptide concentration during insulin treatment correlated with the change in blood glucose. Fasting serum C peptide concentrations correlated closely with the 24-h C-peptide area under the curve. In conclusion, insulin treatment of NIDDM patients with secondary failure to oral agents greatly reduces the insulin secretion, probably owing to the reduction in blood glucose. PMID- 1642080 TI - Urinary excretion of 19-noraldosterone, 18, 19-dihydroxycorticosterone and 18 hydroxy-19-norcorticosterone in patients with aldosterone-producing adenoma or idiopathic hyperaldosteronism. AB - Urinary excretion of 19-noraldosterone, 18. 19-dihydroxycorticosterone (18, 19(OH)2-B), 18-hydroxy-19-norcorticosterone (18-OH-19-nor-B), 18 hydroxycorticosterone (18-OH-B), 18-hydroxycortisol (18-OH-F) and aldosterone were measured in 25 patients with primary aldosteronism, 16 with an aldosterone producing adenoma and 9 with idiopathic hyperaldosteronism. In patients with idiopathic hyperaldosteronism, urinary 19-noraldosterone (207 +/- 51 pmol/day), 18, 19(OH)2-B (21 +/- 4.2 nmol/day) and 18-OH-19-nor-B (879 +/- 213 pmol/day) levels were lower but not significantly different from 19-noraldosterone (263 +/- 56 pmol/day), 18, 19(OH)2-B (40 +/- 8.7 nmol/day) and 18-OH-19-nor-B (1322 +/- 267 pmol/day) seen in patients with aldosterone-producing adenoma. Urinary aldosterone did not differ significantly between patients with idiopathic hyperaldosteronism and those with aldosterone-producing adenoma. Both urinary 18 OH-B and 18-OH-F excretion were significantly higher in aldosterone-producing adenoma (39 +/- 5.2 nmol/day, 1660 +/- 318 nmol/day, respectively) compared with patients with idiopathic hyperaldosteronism (19 +/- 3.3 nmol/day, 541 +/- 93 nmol/day, respectively) (p less than 0.05). Though urinary 18-OH-F and 18-OH-B concentrations were useful markers, the mineralocorticoid steroids which we can only now measure, 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. PMID- 1642081 TI - Cabergoline in the long-term therapy of hyperprolactinemic disorders. AB - The efficacy and safety of the new long-acting dopamine agonist cabergoline were evaluated in 127 hyperprolactinemic patients (124F and 3M; 71 with microprolactinoma, 14 with macroprolactinoma, 5 with operated macroprolactinoma and 37 with idiopathic disorder) who were treated with the drug for from 3 to 52 months (median, 14 months). Cabergoline was administered orally at dose levels ranging between 0.2 and 3.5 mg per week, given once weekly in 92 patients, twice weekly in 22, thrice weekly in 9 and daily in 4. Serum prolactin and progesterone levels, hematology, blood chemistry and electrocardiograms were frequently evaluated throughout treatment. CT or MR imaging of the pituitary was repeated during treatment in patients with macroprolactinoma and in 38 with microprolactinoma. After drug discontinuation, serum prolactin and gonadal function were evaluated monthly for three months in 65 patients and for up to two years in 12. Serum prolactin levels were normalized in 114 patients (90%). Of 56 women with amenorrhea, 52 resumed menses (with presumptive evidence of ovulation in 49); 17 women became pregnant; and sexual potency was restored in the 3 men. Evidence of tumor shrinkage was obtained in 13 of the 14 patients with macroprolactinoma and in 28 of 38 with microprolactinoma; complete disappearance of the tumor image was achieved in 2 macro and 14 microprolactinomas. A total of 48 adverse events was reported by 29 patients (23%), almost all typical of the pharmacological class and mild to moderate; no patient withdrew from treatment due to adverse events. Safety parameters did not change. Following cabergoline discontinuation, prolactin levels increased slowly, being still markedly lower than pretreatment values after three months; 10 patients out of 32 had persistently normal prolactin levels during one year of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642082 TI - Development of Graves' disease after subacute thyroiditis: two unusual cases. AB - This report describes two unusual cases of subacute thyroiditis from which Graves' disease with hyperthyroidism developed seven to eight years after complete recovery. The first case is a 45-year-old woman who developed hyperthyroidism seven years after recovering from subacute thyroiditis. This patient had a genetic predisposition to both subacute thyroiditis HLA-BW35 and Graves' disease (HLA-BW46). The second case is a 60-year-old woman who developed hyperthyroidism eight years after the episode of subacute thyroiditis; her HLA showed neither BW 35 nor BW 46. It has been reported that if hyperthyroidism is to develop following subacute thyroiditis it occurs within one year. Our observation indicates that it may occur seven or eight years later. PMID- 1642083 TI - A normal ovulatory woman with hyperprolactinemia: presence of anti-prolactin autoantibody and the regulation of prolactin secretion. AB - We present the case of a normal ovulatory woman with marked hyperprolactinemia and no evidence of a pituitary adenoma on CT and MRI. Gel filtration studies showed that most immunoreactive PRL was eluted as 150K-170K macroprolactin. Anti PRL autoantibody was detected and Scatchard analysis revealed a low-affinity (the association constant: 1.29 x 10(7) l/mol), high-capacity (the maximal binding capacity: 1174 micrograms/l) antibody. Dopamine had little suppressive effect on PRL levels and an antidopaminergic agent elicited an augmented response of PRL secretion. These results suggest that the presence of anti-PRL autoantibody may delay the clearance of PRL and/or may alter the central regulation of PRL secretion. PMID- 1642084 TI - Presence of aldosterone-like immunoreactivity in cerebrospinal fluid in normotensive subjects. AB - Accumulating evidence, including a wide distribution of specific receptors for aldosterone in the brain, has revealed a potential role of aldosterone in the central nervous system. However, whether or not aldosterone is present in cerebrospinal fluid remains unclear. We attempted to detect aldosterone in cerebrospinal fluid in 14 normotensive subjects. Cerebrospinal fluid was obtained by lumbar puncture. Aldosterone-like immunoreactivity was detected in cerebrospinal fluid (163 +/- 5 pmol/l, range 139-211 pmol/l) and was found to significantly correlate to both plasma aldosterone (r = 0.70, p less than 0.01) and plasma renin activity (r = 0.68, p less than 0.01). However, no significant relationship was found between aldosterone-like immunoreactivity in cerebrospinal fluid and the level of sodium or potassium in cerebrospinal fluid or mean blood pressure. Although we confirmed the presence of aldosterone-like immunoreactivity in cerebrospinal fluid of normotensive subjects, the physiological role of aldosterone in cerebrospinal fluid has yet to be elucidated. Further study will thus be needed to determine the role of cerebrospinal fluid aldosterone. PMID- 1642086 TI - Effect of testosterone on bone mineralization of the hypophosphataemic rat. AB - Clinical observations in patients with X-linked hypophosphataemic rickets, that bone changes can be corrected during puberty, suggest that androgen can participate actively in the process of bone mineralization. In the present study we investigated the role of testosterone on the bone mineralization of male rats placed on a low phosphorus and vitamin D diet and kept in complete darkness after weaning. After 15 days the animals presented hypophosphataemia, rickets and osteomalacia, as assessed by histomorphometry of the tibia and seventh caudal vertebra calcification fronts respectively. Testosterone propionate administration for five days, while the animals were kept on the same rachitogenic diet, induced an improvement in the bone mineralization process of the hypophosphataemic rat independently of serum phosphate levels. Testosterone treated rats were cured of rickets but not of osteomalacia, despite the reduction in osteoid seam area. PMID- 1642085 TI - Regulation of parathyroid hormone release in normal and pathological parathyroid cells exposed to modulators of protein kinase C. AB - Effects of the protein kinase C activating phorbol ester 12-O-tetradecanoyl phorbol 13-acetate and the inhibitor 1-(5-isoquinolinyl-sulfonyl)-2 methylpiperazine (H-7) on parathyroid hormone (PTH) release were studied in normal bovine and pathological human parathyroid cells. An increase of extracellular Ca2+ from 0.5 to 3.0 mmol/l inhibited PTH release by 60% in the bovine cells with half maximal effect (ED50) at 1.31 mmol/l. This inhibition reached less than 50% in the cells from patients with primary and uremic hyperparathyroidism, and the ED50 values were 1.49 and 1.42 mmol/l, respectively. The phorbol ester (0.1 mumol/l) made secretion insensitive to changes of extracellular Ca2+, an action counteracted by H-7 (50 mumol/l) in the bovine cells, whereas H-7 alone had no effects. The phorbol ester and H-7 had opposite actions on regulation of PTH release also from cells from patients with hyperparathyroidism. However, in pathological cells H-7 alone improved Ca2+ inhibition of secretion by stimulating release in low Ca2+ concentrations and decreasing the ED50 values. The magnitude of changes in ED50 values by H-7 increased with the severity of the secretory disturbance of the pathological cells. The results indicate that increased protein kinase C activity may be a factor of importance in the pathophysiology of hyperparathyroidism. PMID- 1642087 TI - The effects of goitrogenesis, involution, and goitrogenic rechallenge on the clonogenic cell content of the rat thyroid. AB - A fraction of enzymatically monodispersed rat thyrocytes from untreated animals clonally proliferate into thyroid follicular units following transplantation into the subcutaneous fat pads of syngeneic recipients. During the induction of experimental goiters in rats either with 3-amino-1,2,4-triazole/iodine sufficient diet or KClO4/Remington low iodine diet, the clonogenic fractions of cells from aminotriazole goiters decreased to 1.9 x 10(-4) and KClO4 goiters to 9.8 x 10(-5) as compared to 5.8 x 10(-3) for cells from age-matched controls during the growth phase of goitrogenesis. With continued aminotriazole treatment after thyroid hyperplasia had ceased, the clonogenic fraction increased to 2.0 x 10(-3) while continued KClO4 treatment had little further effect. The changes in the clonogenic fraction induced by both regimens were reversed during involution; goitrogenic rechallenge of involuted glands led to changes in the clonogenic fraction similar to that noted during the initial challenge. The clonogenic fractions of cells from aminotriazole goiters were greater than that of cells from KClO4 goiters at all time points examined despite similar TSH levels in situ. We conclude that the rat thyroid contains a hierarchy of cells with different proliferative capacities and that the clonogenic thyrocytes possess many of the attributes of a stem-cell. PMID- 1642088 TI - Recombinant human growth hormone stimulates B cell immunoglobulin synthesis and proliferation in serum-free medium. AB - In order to investigate the effects of growth hormone on human B cells, we studied immunoglobulin synthesis and [3H]-thymidine uptake by B cell lines, IM-9, GM-1056 and CBL, and purified tonsil B cells. Cells were cultured in a serum- and albumin-free medium, Cosmedium-001 to exclude interaction between a certain growth-promoting substance and any unknown substances that serum may contain. GH enhanced IgG synthesis and [3H]-thymidine uptake by IM-9 cells, IgA synthesis by GM-1056 cells and IgM synthesis by CBL cells in a dose-dependent fashion. This was not a non-specific effect of protein in GH, since equivalent or higher concentrations of proteins such as bovine serum albumin, interleukin-2, interleukin-5, granulocyte/macrophage colony-stimulating factor, or erythropoietin did not stimulate B cell lines. Moreover, the rabbit anti-GH antibody blocked the enhancing effect of GH, while normal rabbit antibody failed to do so. GH also enhanced immunoglobulin synthesis (IgG and IgM) and thymidine uptake by Staphylococcus aureus Cowan strain I-activated tonsil B cells. These results indicate that GH has a direct stimulating effect on B cells, and, in addition to its endocrinological function, GH may also act as an immunoregulatory cytokine. PMID- 1642089 TI - Ovarian and circulating levels of oxytocin and arginine vasopressin during the estrous cycle in the rat. AB - Ovarian extracts of Long-Evans rats separated using high performance liquid chromatography (HPLC) were measured by radioimmunoassays (RIAs) for the presence of oxytocin and arginine vasopressin (AVP). The results showed that the ovary contains both, and that they are indistinguishable from the respective standard synthetic peptides. During the estrous cycle, the ovarian content of oxytocin was 10-fold higher (p less than 0.01) in estrus than in the other phases, while AVP was 16- and 25-fold higher (p less than 0.01) in metestrus than in the other phases. In contrast, the plasma levels of oxytocin showed no significant difference among the various phases of the estrous cycle. However, the plasma level of AVP level was significantly higher (p less than 0.01) in diestrus than in other phases. The present study thus strongly supports the hypothesis that both oxytocin and AVP can be produced by the ovary itself in the rat. The possible roles of oxytocin and AVP in the reproductive cycle are discussed. PMID- 1642090 TI - Effect of growth factors on hyaluronan and proteoglycan synthesis by retroocular tissue fibroblasts of Graves' ophthalmopathy in culture. AB - One of the pathological changes seen in Graves' ophthalmopathy is the deposition of glycosaminoglycans such as hyaluronan and proteoglycan in retroocular connective tissue. We analyzed glycosaminoglycans synthesized by retroocular tissue fibroblasts in culture derived from an individual not suffering from thyroid disease and from three patients with Graves' ophthalmopathy. Retroocular tissue fibroblasts synthesized both hyaluronan and proteoglycan, the latter composed mainly of chondroitin sulfate. This contrasts with the proteoglycan synthesized by adult skin fibroblasts which was composed of dermatan sulfate and heparan sulfate proteoglycan. Chondroitin sulfate proteoglycan secreted by retroocular tissue fibroblasts consisted of large and small chondroitin sulfate proteoglycans (CS-PG), their size being determined by the Sepharose CL-6B column. The effects of IGF-1 and PDGF on hyaluronan and proteoglycan synthesis were studied separately and in combination. Both IGF-1 and PDGF increased the synthesis of hyaluronan and proteoglycan in a dose-dependent manner. IGF-1 predominantly stimulated secretion of small CS-PG, while PDGF increased large CS PG markedly when studied in retroocular tissue fibroblasts. In contrast, IGF-1 stimulated secretion of small proteoglycan while PDGF had little effect on proteoglycan synthesis in skin fibroblasts. Thus, glycosaminoglycan synthesized by retroocular tissue fibroblasts has a unique composition and each component is regulated independently, at least in part. PMID- 1642091 TI - Prognostic relevance of morphological classification in multiple myeloma. AB - One hundred and twenty-two patients with multiple myeloma were classified as mature, intermediate, immature, or plasmablastic subtype according to Greipp's criteria. Contrary to Greipp's report, the survival time of plasmablastic myeloma was not significantly shorter than other subtypes, nor was the plasmablastic subtype identified as a poor prognostic factor. The survival time of mature plus intermediate myeloma was significantly longer than that of immature plus plasmablastic myeloma. Between the former and latter, significant differences were found for sex, clinical stage, thrombocytopenia, bone marrow plasmacytosis, renal insufficiency, bone destruction, and response rate to treatment. Therefore, it was suspected that the immature and plasmablastic subtypes were unfavorable prognostic factors in patients with multiple myeloma. PMID- 1642092 TI - Recurrence of Hodgkin's disease after 10 years: observation of 5 cases. AB - Five patients whose Hodgkin's disease recurred 10 years or more after the achievement of complete remission are reported. Four out of 5 patients had shown an advanced stage at the onset of disease and therefore had received combination chemotherapy (ABVD or MOPP-like) as primary treatment. Involved-field irradiation was delivered as consolidation therapy in 1 patient only. All pathologically proven relapses occurred in a previously affected area and the histologic subtype differed from the primary subtype. The time interval between the achievement of the first complete remission and the relapse was 120, 170 and 190 months in 3, 1, and 1 patient, respectively. All 5 patients are alive in second complete remission. This paper emphasizes the risk of late relapse even after a prolonged disease-free interval for patients with Hodgkin's disease. Close follow-up is therefore recommended also in this clinical setting. PMID- 1642093 TI - Normal fluctuations of leucocyte counts and the response to infection in benign familial leucopenia. AB - In a long-term follow-up of 47 Yemenite patients with benign familial leucopenia, the mean white-cell count was 4,578 with a standard deviation of 940. During bacterial infections, the average leucocyte increment was the same in leucopenic as in non-leucopenic subjects, leading to total leucocyte counts in the normal range in previously leucopenic subjects. The marked degree of variability makes clinical interpretation difficult when leucocyte counts are found between levels standardised as normal in sick patients previously known to be leucopenic. PMID- 1642095 TI - HbH disease associated with the (--MED) deletion in a Brazilian black woman. AB - Clinical, laboratory features and restriction enzyme DNA analysis are reported for a black Brazilian woman with HbH disease. The patient presented a thalassemic blood picture with HbH and Hb Bart's. Gene mapping demonstrated the compound heterozygous state for the --MED and -alpha 3.7 deletions. PMID- 1642094 TI - Identification of GATA-1 and NF-E2 binding sites in the flanking regions of the human alpha-globin genes. AB - Some of the elements involved in the erythroid-specific transcriptional regulation of the human gamma- and beta-globin genes and located inside or in the immediate proximity of these genes have been identified as sequences which bind erythroid-specific factors. In the present study, we found two regions located within 1 kb in 5' to the alpha 2- and in 3' to the alpha 1-globin genes which contribute to the induction of human alpha-globin genes following erythroid differentiation in stable MEL transformants. By DNAse I footprinting and gel mobility shift assays, we identified several GATA-1 and one AP-1/NF-E2-binding sites located inside these regions. These results strengthen the idea that, like for all other globin genes, flanking regions contribute in vivo to the regulation of human alpha-globin gene expression. PMID- 1642096 TI - Treatment of methimazole-induced severe aplastic anemia with recombinant human granulocyte-monocyte colony-stimulating factor and glucocorticosteroids. AB - The in vivo response to recombinant human granulocyte-monocyte colony-stimulating factor (rHu GM-CSF) in facilitating the reconstitution of granulomonopoiesis was evaluated in a patient with Graves' disease who developed severe aplastic anemia during methimazole therapy. After 10 days of treatment with rHu GM-CSF, the neutrophil and monocyte counts rose to 1.65 x 10(9)/l and 0.41 x 10(9)/l, respectively. However, the patient was still dependent on erythrocyte and platelet transfusions. Two days after rHu GM-CSF withdrawal, the neutrophil count dropped off to 0.41 x 10(9)/l.rHu GM-CSF was reinitiated for 2 days along with glucocorticosteroids. With this combined therapeutic approach, the neutrophil count returned to normal and remained stable, and both Hb and platelet values began to improve. It is concluded that the combination of rHu GM-CSF and glucocorticosteroids can be used as a therapeutic option that may lead to beneficial results in drug-induced aplastic anemia. PMID- 1642098 TI - Central nervous system involvement in prolymphocytic transformation of chronic lymphocytic leukemia. PMID- 1642099 TI - A case of adult T cell leukemia complicated by monoclonal gammopathy in the course of chemotherapy. PMID- 1642097 TI - Neonatal alloimmune thrombocytopenia due to HLA-A2 antibody. AB - A male, full-term baby with thrombocytopenia was born by a G3P2A1 mother who was not associated with autoimmune disease. Platelet antibody screening was positive by using lymphocytotoxicity test, platelet suspension immunofluorescence test and solid-phase red cell adherence test. The identified HLA antibody was of A2 specificity. It was confirmed by testing the mother's and the baby's sera against the lymphocytes and platelets of 10 HLA-A2-positive donors. The possibility of platelet-specific antibody as the cause of neonatal alloimmune thrombocytopenia was ruled out by testing against platelets of 10 HLA-A2-negative donors and the known platelet-specific antigens utilizing immobilized, purified platelet glycoprotein as targets. The mother's serum reacted strongly with both the father's and the baby's platelets and lymphocytes. This neonatal thrombocytopenia was most likely due to the maternal HLA antibody, which was induced by her antecedent gestations. PMID- 1642100 TI - Chemotherapy-induced neutrophilic eccrine hidradenitis in acute myeloid leukemia. PMID- 1642101 TI - [Histochemical light and electron microscopic investigations on an eosinophilic granuloma]. AB - An eosinophilic granuloma has been investigated by means of histochemical proofs for enzymes and tissue elements and common staining methods. The best method was be found the proof for the enzyme phenol oxidase (EC 1.14.18.1). In this way it is possible to determine eosinophils rapidly and surely and to receive an overview on the frequency and distribution of these cells. The histiocytic-like cells was identified electron microscopical as Langerhans' cells. This cells are in narrow contact to many eosinophilic granulocytes. Their granula have manifold changes in their structure. The granula are possibly able to produce new structures of the cell. The eosinophilic granuloma correspond to a cell mediating immunological defence reaction approximate to the type of a delayed hypersensitivity. PMID- 1642102 TI - Histochemical detection of sugar residues in chick embryo developing lingual glands with horseradish-peroxidase conjugated lectins. AB - Tongue anlage were taken in chick embryos from the 7th to the 21st d of incubation and in 3 d old chicken. A battery of 7 different horseradish peroxidase-conjugated lectins (PNA, ConA, DBA, SBA, LTA, WGA, UEA I) was used to study the carbohydrate residues of glycoconjugates at the epithelial cells of the anterior and posterior lingual glands. Some sugar residues, detected at the surface of the epithelial cells in early developmental stages of glandular primordia, seemed to play a role in inducing and regulating the first differentiative steps of the glands. Differences in type, amount, time of appearance and cellular localization between the 2 groups of glands were detected. The group of the anterior lingual glands, adjacent to the entoglossal cartilage (paraentoglossal glands), showed some peculiar histochemical characteristics. PMID- 1642103 TI - [Histochemical investigations on the localization of acetylcholinesterase in the kidney of selected vertebrates]. AB - The light and electron microscopical localization of AChE activity in the kidney of selected vertebrates was studied using the method of Karnovsky and Roots (1964) for light microscopy and the modification of the Koelle and Friedenwald's technique according to Tsuji (1974, 1984) for electron microscopy. AChE activity could be demonstrated light microscopically mainly within the glomeruli of some mammals (golden hamster, mouse, rat) and non-mammalian vertebrates (carp, frog). No activity was found in the glomeruli of guinea pig, of chicken and tortoise. In the mammalians, the strongest AChE activity could be demonstrated in the guinea pig, the lowest in the rat. A strong AChE enzyme activity was also detected within the interlobular arteries and the cells of Bowman's capsule. With the electron microscopical method AChE activity was demonstrated in mesangial cells and endothelial cells of the glomeruli (golden hamster and carp) and in the cells of Bowman's capsule (carp). Reaction product was localized within the cisterns of endoplasmic reticulum and the perinuclear space (nuclear envelope). A high amount of electron opaque material could be observed in the cells of Bowman's capsule and their lamina basalis. The functional significance of the localization of AChE activity in the glomeruli will be discussed. PMID- 1642104 TI - [Histochemical and immunohistochemical investigations of the perivascular nerves in rat colonic mucosa]. AB - Using histo- and immunohistochemical methods and conventional transmission electron microscopy (TEM), perivascular nerves of the rat colonic mucosa were investigated. We found that the nerve endings and varicosities operate with various transmitter substances. The morphological findings show that cholinergic and peptidergic nerves are localized around all kinds of terminal microcirculation vessels, while noradrenergic nerves are encountered only near arterioles and venules. PMID- 1642106 TI - Pitfalls in the histochemical demonstration of alpha-glucan phosphorylase activity in glycogen-depleted skeletal muscle fibres. AB - In the present communication, an investigation is described into the reliability of histochemical methods for the demonstration of alpha-glucan phosphorylase activity in glycogen-depleted skeletal muscle fibres. Human skeletal muscles with glycogen-depleted fibres from patients with diseases of the neuromuscular system and from subjects who had suffered from malignant hyperthermia were used for the study. The location of phosphorylase activity and glycogen was demonstrated with histochemical techniques. Biochemical techniques were used to assay the activity of phosphorylase and the content of glycogen. Biochemical determinations of phosphorylase activity did frequently not reveal significant differences between glycogen-depleted and non-depleted skeletal muscle fibres. In contrast, all histochemical methods investigated, showed little or no phosphorylase activity in the glycogen depleted fibres, indicating that none of the existing histochemical methods revealed reliable staining results in these fibres. Owing to the invalid staining results of the histochemical methods for glycogen-depleted muscle fibres, it is necessary that for metabolic studies a biochemical assay for phosphorylase activity is also to be performed. PMID- 1642105 TI - Developmental regulation of lectin-binding patterns in Paracentrotus lividus gonads, gametes, and early embryos. AB - By use of several lectins (ConA, WGA, SBA, GS I, PNA), a study was carried on gametes and developing embryos of the sea urchin Paracentrotus lividus, to investigate developmental changes in cell surface, leading to changements in cell environment interactions. ConA, WGA, and SBA, with high affinity, bind to the vitelline membrane of unfertilized eggs, while PNA labelling at the same site is weak; GS I-binding is only present in the cytoplasm and cortical region of the unfertilized eggs. Immediately after fertilization, no ConA-binding is present in the membrane, while WGA- and SBA-binding molecules are located in the fertilization layer. In zygotes, 40 min after fertilization, ConA affinity sites were again present in both cytoplasm and cortical region. During cleavages and gastrulation, ConA binds to the blastomere cytoplasm and cortical region, to the intercellular matrix, and to the cytoplasm of mesenchyme cells. WGA binds to the cortical region of cleaving blastomeres, including the hyaline layer, up to the unhatched blastula. Then it labels the gastrula inner and outer surfaces. SBA binds to the blastomere membranes; no GS I- and PNA-binding was detected during embryonic development. Sperms are bound by all the lectins, except GS I. Mannose and glucose conjugates are the most represented throughout the whole development of P. lividus, and their origin and locations are developmentally regulated. Galacto-residues are scarcely represented or are masked by other terminal sugars (e.g. sialic acid), and become functional during particular developmental events (cell movements). PMID- 1642107 TI - Histomorphological and cytochemical changes induced in the liver of goldfish Carassius carassius var. auratus by short-term exposure to lead. AB - The cellular and molecular effects of experimental lead intoxication (5 mg l-1/24 h and 48 h) were studied in hepatocytes of Carassius carassius var. auratus. Significant lead storage was not detected by atomic absorbance spectroscopy after treatment. Cell morphology appeared only poorly impaired. A decrease of glycogen content was observed. Glycolysis, Krebs cycle and pentose shunt were altered in their enzymatic activities. Lysosomal activities were strongly increased. All enzymatic activities tested were altered 24 h after lead treatment. PMID- 1642108 TI - Differential diagnosis between dementia and depression: a study of efficiency increment. AB - A battery of neuropsychological tests was examined to establish its value in differentiating mild dementia from depression. The battery was applied to 84 subjects: 31 dementia patients of several etiologies, 31 patients with major depression and 22 volunteers whose age and educational level was similar to that of the patients. The battery consisted of tests for immediate, recent and remote memory, the Mini Mental State examination, a screening test for language disorders, and tests measuring abstraction, calculation, judgement, praxic and gnosic functions. The results showed significant differences among the three groups in all memory tests. Deficits of abstraction, calculation, praxis and language functions were strongly associated with dementia. The epidemiological analysis of efficiency increment, with determination of sensitivity and specificity, showed a highly significant enhancement of efficiency for diagnostic purposes when the results of the tests were combined. These findings suggest that the entire battery of neuropsychological tests should be applied, and their results compared using the efficiency increment procedure, in order to establish a firm differential diagnosis between dementia and depression, and/or to detect the former when it is at a mild early stage. PMID- 1642109 TI - Correction for age, education and other demographic variables in the use of the Mini Mental State Examination in Finland. AB - The population-based Helsinki Aging Study was comprised of three age groups: 75-, 80- and 85-year-olds. A random sample of 511 subjects completed the Mini Mental State Examination (MMSE) and were assessed on the Clinical Dementia Rating-scale (CDR). According to the CDR results 446 subjects were screened as non-demented. Of these subjects 30% scored below or at 24 MMSE points. Age, education and social group had a significant effect on the MMSE scores, even after excluding the demented cases. Together they explained 10% of the total variance within the MMSE. Social group correlated with education. The MMSE scores were corrected according to age and education. Adjustment of the originally used cutpoint of 24 resulted in cutpoints of 25 and 26 among the 75-year-olds, in the low and high education groups respectively; 23 and 26 in the 80-year-olds; 22 and 23 in the 85 year-olds. PMID- 1642110 TI - Benign monomelic amyotrophy of lower limb: report of three cases. AB - Three patients with wasting confined to a single lower limb are reported. The characteristic features were: sporadic occurrence, insidious onset with slow progression and in 2 cases arrested course for at least 4 years, wasting out of proportion with disability, absence of sensory, pyramidal tract or bulbar signs. CK, motor and sensory conductions, and lumbar MRI were normal. Muscle CT showed selective loss of muscle tissue and fat replacement in posterior leg muscles. Quantitative electromyography and histologic findings revealed neurogenic features not only in the affected legs, but also in clinically uninvolved limbs. Monomelic amyotrophy of lower limb is a variant of spinal muscular atrophy with a benign course. However, as in the early stages of the disease there are no distinctive clinical or laboratory findings with other motor neuron diseases, the diagnosis of monomelic amyotrophy may be made only retrospectively after a prolonged observation. PMID- 1642111 TI - Primary intranasal encephalocele: a rare cause of bacterial meningitis. AB - In four patients with bacterial meningitis a primary intranasal encephalocele was found as portal of entry. In two of the cases the malformation had been misdiagnosed as a nasal polyp and operated upon. In two patients a cerebrospinal fluid fistula developed spontaneously at the age of 54 years. None of the patients had associated symptoms indicating the presence of a cleft. Encephaloceles can be readily visualized by computed tomography particularly in coronal sections. The treatment of choice is transcranial surgical repair. PMID- 1642112 TI - Migration and age at onset of multiple sclerosis: some pitfalls of migrant studies. AB - The aim of this study was to compare age at onset of multiple sclerosis (MS) in North African-born and French-born patients. The migrant group consisted of 246 patients who arrived in France during the period 1960-1965. Among these migrants, 27 (11%) had first symptoms before migration. The French-born group consisted of MS patients of same sex and age at the time of the study as migrants who were randomly selected from a large national sample. After controlling for various biases which could explain differences between migrants and French-born patients, we found no differences in mean age at MS onset between the two groups. Therefore, it is likely that MS was acquired by the same age in migrants as in French-born patients. This finding may constitute an indirect support for the hypothesis that the unknown causative factors of MS are equally frequent whatever the latitude of origin. PMID- 1642113 TI - Cerebral ischemia associated with anticardiolipin antibodies. AB - Eight patients, 3 with systemic lupus erythematosus (SLE) or "SLE-like" disease, 1 with sarcoidosis, and 4 with no connective tissue disease had transient ischemic attacks (TIA) or cerebral infarctions associated with high levels of anticardiolipin antibodies (ACA). Cerebral ischemic events included amaurosis fugax, recurrent hemispheric TIA, cerebral infarction, and multi-infarction dementia. Treatment with acetylsalicylic acid was ineffective in 3 patients. Warfarin, alone or in combination with dipyridamole or steroids, may reduce the risk of further cerebrovascular events. PMID- 1642114 TI - Effects of oxcarbazepine and carbamazepine on the central nervous system: computerised analysis of saccadic and smooth-pursuit eye movements. AB - Oxcarbazepine (OXC) is a new anti-epileptic agent structurally related to carbamazepine (CBZ). OXC seems to have a similar efficacy and a better tolerability profile than CBZ. In the present study we compared the subclinical side-effects on the CNS of OXC and CBZ using a computerised analysis of saccadic and smooth-pursuit eye movements. Six healthy male volunteers (mean age 29 yrs) participated in the study, which was conducted by a double-blind cross-over design. Each subject was given a single dose of either CBZ 400 mg or OXC 600 mg (according to the random assignment) after which the drug effects on eye movements were evaluated. One week later, the trial was repeated using the other drug. The parametrisation of both saccadic and smooth-pursuit eye movements was carried out by measuring a series of performance parameters [e.g. the maximum saccade peak velocity (MSPV) and the typical target velocity (TTV)]. OXC was found to induce a lesser degree of alteration on the values of both MSPV (p = 0.07) and TTV (p less than 0.03) than CBZ. In particular, the TTV values were virtually unaffected by OXC administration, while the effects of CBZ on both variables were particularly evident at 8 and 10 h after dosing which correspond to the time at which the plasma concentrations of CBZ and of its 10,11-epoxide reach the peak. In conclusion, our preliminary results indicate that OXC induces negligible alterations, if any, on the eye movement parameters evaluated in our study. PMID- 1642115 TI - Mobius syndrome with basal ganglia calcification. AB - Basal ganglia calcification has not been described in Mobius syndrome. A family with two children with Mobius syndrome are reported. Bilateral basal ganglia calcification was seen on computed tomography in both. This is the first family where cerebral involvement has been clearly documented in this syndrome. PMID- 1642116 TI - Diagnosis of sympathetic pupilomotor dysfunction (Horner's syndrome) PMID- 1642117 TI - Progressive senile dementia Alzheimer type (SDAT) PMID- 1642118 TI - [Otorhinolaryngologic surgery in Flanders from the Renaissance to the 18th century. A brief overview]. PMID- 1642119 TI - [The beginnings of otorhinolaryngology in Belgium in the 19th century]. PMID- 1642121 TI - A community-based study of survival in dementia. AB - The objective of this study was to compare the mortality rate of demented and nondemented subjects in a single cohort. We followed up a cohort of subjects comprising all 1259 inhabitants of Leiden aged 85 years and over, evaluated earlier for the presence of dementia, and including institutionalized subjects. The main outcome measure was the mortality rate ratio of the demented and nondemented groups adjusted for age and sex. The mortality rate ratio of the demented vs the nondemented group was 1.9 (95% confidence interval: 1.7-2.2). No difference in mortality rate was found between those with mild vs moderate to severe dementia. The mortality rate in dementia patients is higher than in nondemented subjects. PMID- 1642120 TI - The psychological management of depression. AB - This article reviews the effects of psychological treatments specifically developed for depression. Promising and durable results have been reported for cognitive and interpersonal psychotherapies but also for behavioral psychotherapy, which has generated less research interest so far. The therapeutic effects seem to be equivalent and at least comparable to pharmacotherapy in mild to moderate depression. PMID- 1642122 TI - Specific skills and social competence in schizophrenia. AB - Generalization of skills is a major problem in social skills training for schizophrenic patients. Assessment of skills is mostly not based on objective indices of specific skill deficits. The results of this study show that global competence of schizophrenics can be differentiated from specific competence. Global competence was found to be related to symptoms, whereas specific competence was not. No support was found for the assumption that social dysfunctions are caused by negative symptoms. Social perception and positive symptoms did explain a substantial part of the variance of global competence. It is therefore concluded that neither global incompetence nor negative symptoms should be used as an indication for social skills training. PMID- 1642124 TI - Bright dawn simulation compared with bright morning light in the treatment of winter depression. AB - In a randomized cross-over design, 7 patients with winter depression were treated with a week of a bright (1700 lx) dawn simulation (0400 to 0600) and a week of standard bright (1700 lx) morning (0600 to 0800) light therapy. The Hamilton Rating Scale for Depression scores decreased significantly for the standard light therapy (18.9 to 6.6) but not for the bright dawn therapy (18.0 to 11.3). Early morning awakening was a frequent side effect with the bright dawn simulation. Although dawn simulation at a lower illuminance may be an effective treatment, the bright dawn used in this study showed only a nonsignificant trend to lower depression ratings. The illuminance of dawn simulation should be adjusted to minimize side effects. PMID- 1642123 TI - Genetic epidemiological study of schizophrenia: reproduction behaviour. AB - Data from the Tomsk Epidemiological Register and epidemiological family sample were used to study the relationship between schizophrenics' reproductive behaviour (marital status and fertility rate), severity of ICD-9 schizophrenia and risk of illness among relatives of probands. The results are interpreted in terms of multifactorial threshold and single monolocus models. Their importance for the interpretation of epidemiological data (a change of prevalence rate, cohort effect and clinical polymorphism) is discussed. PMID- 1642125 TI - Sex differences in problem drinking among 42-year-old residents of Malmo, Sweden. AB - The main objective was to describe sex-related differences in rates of nonidentified vs identified problem drinking in 42-year-old Malmo residents. All 1264 women and 1368 men born in 1941 were invited to a health screening at the Preventive Medicine Section, Malmo General Hospital. Individuals registered at the Department of Alcohol Diseases because of problem drinking prior to screening (identified problem drinkers) were excluded and analyzed separately. Intervention in the remaining subjects was made if any of 3 sets of inclusion criteria was met. The sex ratios (female:male) of identified and nonidentified problem drinking were 1:4.1 and 1:2.8 respectively. Thus, nonidentified problem drinking is by and large proportional to identified problem drinking in both sexes, arguing against hidden drinking being and exclusively female phenomenon. PMID- 1642126 TI - Comparison of Composite International Diagnostic Interview and clinical DSM-III-R criteria checklist diagnoses. AB - This article describes a comparison of Composite International Diagnostic Interview (CIDI) diagnostic results and results based on clinicians' observation of CIDI assessments. Psychiatrists scored a DSM-III-R criteria checklist either while observing or after administering 20 CIDI interviews. Overall diagnostic concordance between the checklist and CIDI diagnoses was found to be good (kappa = 0.78). Good diagnostic agreement was also found for 3 groups of DSM-III-R disorders: depressive disorders (kappa = 0.84), psychoactive substance use disorders (kappa = 0.83) and anxiety phobic disorders (kappa = 0.76). These results are consistent with the results from a similar comparison between the CIDI and checklist results for ICD-10 diagnoses. PMID- 1642127 TI - Low level of antidepressant prescription for people who later commit suicide: 15 years of experience from a population-based drug database in Sweden. AB - The use of antidepressants has been low in Jamtland County for many years, while the suicide rate has been among the highest in Sweden. A continuous outpatient prescription recording system has been in operation in Jamtland since 1970. Through this system we traced the prescription pattern of 80 individuals who committed suicide from 1970 to 1984. Suicide patients obtained 1.5 times more prescription drugs than 80 matched controls, mainly psychotropics and vitamins. During the 3 months prior to the suicide, half of the patients had received medical attention and 73% of the women and 40% of the men had obtained prescription drugs, in one-third from the psychiatric department. While 53% and 29%, respectively, obtained psychotropic drugs, only 13% and 9% respectively were prescribed antidepressants, often in low doses. People who will commit suicide often seek medical help. The low rate of antidepressant prescription in patients committing suicide probably reflects insufficient diagnosis and treatment of depressive disorders. It is urgent--for the individual as well as for society- that diagnostic and pharmacotherapeutic routines be improved. PMID- 1642128 TI - Projective identification and suicide contagion. AB - The effect of suggestion on suicide is well established. However, the intrapsychic mechanisms of the contagion of suicides are poorly understood. In this article I first present the literature about suicide clustering and about projective identification. In the following clinical vignette I try to understand a patient's suicidal behaviour, referring to William Goldstein's clarifying model of projective identification. I aim to illustrate that his model has heuristic value in the treatment of suicidal patients when the effect of suggestion or identification is suspected. PMID- 1642129 TI - Fluvoxamine in the treatment of demented elderly patients: a double-blind, placebo-controlled study. AB - The efficacy of fluvoxamine on cognitive functioning and behavioral changes was evaluated in a double-blind, placebo-controlled study of 46 elderly demented patients. The patients had a DSM-III diagnosis of primary degenerative dementia or multi-infarct dementia and were aged greater than or equal to 65 years. Twenty two patients were given 150 mg fluvoxamine per day and 24 received placebo tablets; 14 and 15 patients, respectively, completed 6 weeks of treatment. Within treatments, there were no significant changes in median scores on neuropsychological tests (picture recall and recognition, trail making and finger tapping) or the GBS scale scores (degrees of dementia) or GBS subscale score (clinical profiles, including symptoms common in dementia, motor, emotional and intellectual functioning). Between treatments, the median changes in psychometric test scores did not differ significantly. However, within and between treatments, there were trends favoring fluvoxamine on symptoms common in dementia (confusion, irritability, anxiety, fear-panic, mood level and restlessness). In conclusion, the study does not support the hypothesis that fluvoxamine improves cognitive functioning or behavioral changes in elderly dementia patients. PMID- 1642130 TI - Cost-benefit analysis of an educational program for general practitioners by the Swedish Committee for the Prevention and Treatment of Depression. AB - In 1983-1984 the Swedish Committee for the Prevention and Treatment of Depression launched an educational program on the diagnosis and treatment of depressive disorders for all general practitioners on the island of Gotland. The baseline year chosen was 1982 and the immediate effects were evaluated in 1985. In 1988 the long-term effects were evaluated. These two evaluations indicated strictly time-related beneficial effects on the frequency of sick leave and inpatient care for depressive disorders, the pattern of prescription of psychopharmacologic drugs and the frequency of suicide. This article describes a cost-benefit analysis of the program. The cost of the educational program, changes in drug prescription and inpatient care were calculated as well as indirect costs concerning changes in morbidity and mortality. The calculation of the savings to society was subject to a sensitivity analysis. This shows that the educational program resulted in savings to society on the order of about SEK 155 million (USD 26 million). It is concluded that educational programs of this kind should be repeated every second to third year. PMID- 1642131 TI - Social conditions in a total population with long-term functional psychosis in three different areas of Stockholm County. AB - A number of social conditions regarding interpersonal relations, housing and employment were studied in a total population of individuals with long-term functional psychosis (n = 341) drawn from the population aged 18-64 years inhabiting three different areas of Stockholm County, altogether about 57,000 inhabitants. Individuals were included irrespective of whether they had a psychiatric treatment contact or not. They were mostly unmarried (57%) and living alone (64%). Most were unemployed (69%) and over half received a disability pension. However, 76% had their own flat and a reasonable financial standard, not deteriorating with illness duration. The diagnosis of schizophrenia led to poorer social conditions, as did early age at onset, male sex and co-morbidity of substance abuse. A larger number of individuals lived in an institution in the urban area while a greater number lived with relatives in the rural area. PMID- 1642132 TI - Posterior fossa abnormalities in major depression: a controlled magnetic resonance imaging study. AB - High-field magnetic resonance (MR) images were used to study posterior fossa morphology in 27 patients with major depression and 36 normal control subjects. Depressed patients demonstrated smaller brain stem and cerebellar vermis than controls. These differences were highly significant for the anterior cerebellar vermis and medulla. There was also a striking age-related decline in midbrain size in depressed patients as well as in controls. Our results are consistent with several lines of evidence implicating a role for the cerebellar vermis in affective disorders and, in addition, provide the first MR documentation of the differential effects of aging on posterior fossa morphology in normal subjects compared with patients with major depression. PMID- 1642133 TI - Urinary excretion of albumin and retinol-binding protein in lithium-treated patients: a longitudinal study. AB - The urinary excretion of albumin and retinol-binding protein was determined by means of sensitive immunochemical methods in a 2-year longitudinal study of 22 lithium-treated patients. During lithium treatment, there were no significant changes in the median albumin:creatinine ratios or retinol-binding protein:creatinine ratios. However, the median albumin:creatinine ratios were significantly higher in lithium-treated patients than in 22 normal subjects, which indicates that glomerular permeability is increased; no correlation with serum lithium level or duration of lithium treatment could be shown. In patients treated with slow-release tablets, the urinary excretion of albumin was significantly higher after 2 years than in patients given lithium carbonate. The median retinol-binding protein:creatinine ratios did not differ significantly between lithium-treated patients and normal subjects, suggesting that lithium does not affect the catabolism of low-molecular-weight proteins in the proximal tubules. In conclusion, the study supports the hypothesis that lithium treatment produces a small but significant and nonprogressive elevation of the urinary excretion of albumin. PMID- 1642135 TI - Can certain stimulus characteristics influence the hemispheric differences in global and local processing? AB - Hemispheric processing of global and local form was examined in two experiments in which the size of hierarchical visual stimuli was manipulated in divided attention tasks. In experiment 1, the subjects were instructed to decide whether or not a symmetrical target (T) was in the visual object presented. In experiment 2, the target to be detected was nonsymmetrical (L). In both studies, global precedence was found depending on stimulus size. When the stimuli subtended about 3 degrees vertically, global dominance was found, but it was not detected when the stimuli subtended about 10 degrees. Experiments 1 and 2 provided evidence against the analytic/holistic dichotomy, presenting the same performance for both hemispheres: the global analysis was much better than the local analysis. When the target was in the global form, both the LH and the RH analyzed the 3 degrees stimuli more efficiently, while both analyzed the 10 degrees stimuli with greater efficiency when the target was in the local form. PMID- 1642134 TI - Neuropsychological and clinical correlates of temporal lobe anatomy in schizophrenia. AB - Twenty-five DSM-III schizophrenic patients were assessed neuromorphologically and neuropsychologically. Reduced temporal lobes were found through magnetic resonance imaging (MRI) evaluation. In addition, in order to look for the neuropsychological correlates of temporal anatomy in schizophrenia, patients were divided into cognitive normal and abnormal schizophrenics, according to their Luria Nebraska Neuropsychological Battery profile. The latter group had statistically significant temporal lobe abnormalities as assessed by MRI, irrespective of medication, clinical picture or any other relevant variables. The implication of such findings in the light of the diaschisis model is discussed. PMID- 1642136 TI - Line bisecting as a predictor of personal optimism and desirability of risky behaviors. AB - Our goal was to test whether current hemisphere predominance is a predictor of scores on standardized measures of personal optimism and preference for risk. In two between-subject experiments, current hemisphere predominance was measured by the direction and extent of line bisecting errors. Pearson correlations and median splits of the line bisecting errors showed significantly greater personal optimism and preference for risk with left hemisphere predominance. These results support previous research in which manipulation of hemisphere predominance produced similar effects on personal optimism in normal individuals and on risk taking in lesioned and normal samples. We conclude that the association of optimism and risk with left hemisphere predominance can be observed in resting as well as in manipulated situations. PMID- 1642137 TI - Follow-ups of children with attention deficit hyperactivity disorder (ADHD). Review of literature. AB - The purpose of this review has been to examine the hypothesis that the Attention Deficit Hyperactivity Disorder (ADHD), formerly also referred to as the Hyperactive Syndrome or Minimal Brain Dysfunction (MBD), is a precursor of criminality and abuse of alcohol and illicit drugs. This has been done by reviewing findings from follow-ups. Most reviewed projects suffer from methodological weakness. In most materials, few if any of the cases had ADHD according to present criteria. Some had ADHD and conduct problems. Many probably had exclusively conduct problems, but were too young to fulfill the criteria of Conduct Disorder (CD). Methodological limitations of the examined projects have been pointed out. It has been discussed how weaknesses regarding research design might have influenced the results. As a consequence of methodological shortcomings of most projects, the reviewed studies do not give definite answers. However, they show some rather convincing trends. By early adulthood, ADHD appears to remain present in at least one third of the subjects. Subjects with prior ADHD did not have more mental problems than controls in adolescence and early adulthood, provided they had normal intelligence, and no additional disabilities or mental disorders. Those with mental retardation, cerebral dysfunction or psychosis in addition to ADHD have a poor prognosis. A high percent become psychotic, and some end up in institutions. Although there seems to be an increased rate of delinquency and lawbreaking in prior hyperactives compared to controls, these differences disappear when the results are analyzed. The initially impressive differences between cases and controls are probably consequences of bias. Cases with a childhood history of conduct and educational problems have been compared to controls without a history of such problems. Thus, the reported differences are not related to ADHD. Hyperactives without conduct problems do not have an increased frequency of delinquency. Problems of conduct, CD and Antisocial Personality Disorder, but not psychosis characterize cases with a childhood history of conduct problems (with or without ADHD). In subjects with ADHD as well as conduct problems in childhood, conduct problems and not ADHD predict the prognosis, which is worse than for those with CD without ADHD. ADHD combined with delinquency indicates a high rate of subsequent lawbreaking. Usually, cases have more problems than controls with alcohol and illicit drugs, but this might be the consequence of selection of cases (subjects with school and conduct problems) and controls (subjects without such problems).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1642139 TI - Excited carbonyl formation in the combination and disproportionation of free radicals. AB - The pyrolyisis of di-tert-butyl peroxyoxalate in the presence of para-substituted benzaldehydes produces almost quantitatively the corresponding p,p'-disubstituted benzils. The formation of these products is accompanied by chemiluminescence arising from excited triplets. From the quantum yield of excited triplet generation and the rate constants for the triplet photocleavage it is possible to obtain the change in Gibbs free energy associated with triplet formation. The values obtained are -5.6, -5.7 and -8.1 kcal/mol for benzil, p,p'-dimethylbenzil and p,p'-dimethoxybenzil, respectively. The pyrolysis of di-tert-butyl peroxyoxalate in the presence of isopropanol or benzoin leads to the formation of acetone and benzil. These products are generated in disproportionation processes involving the alpha-hydroxy radical produced by hydrogen abstraction. The luminescence observed in these reactions constitutes the first experimental indication of excited species generation in the disproportionation of uncorrelated free radicals. PMID- 1642138 TI - Enhanced chemiluminescence in the oxidation of luminol and an isoluminol cortisol conjugate by hydrogen peroxide in reversed micelles. AB - The chemiluminescent oxidation of luminol and an isoluminol cortisol conjugate (ABI-COR) by hydrogen peroxide has been studied in cetyltrimethylammonium bromide (CTAB) reversed micelles in octane-chloroform (1:1). The maximum chemiluminescence intensity of both compounds is dependent on the initial concentrations of the H2O2 and substrates, the pH value of the micelle polar phase and the H2O/CTAB ratio. The optimum pH ranged from 8.5 to 9.5. Under comparable conditions, the chemiluminescence intensity for luminol was 15-fold higher than for the ABI-COR conjugate. A mechanism of oxidation of the substrates in reversed micelles is proposed and the possible mechanisms of inhibition by the substrate and oxidant is discussed. PMID- 1642140 TI - The effect of serine and thiol protease inhibitors on the chemiluminescence of human neutrophils in investigations in vitro. AB - We have studied an indirect role of serine and thiol proteases in the activation of human neutrophils in vitro. Stimulation was evaluated using a chemiluminescence (CL) generation system. Receptor-dependent and receptor independent stimuli were studied, e.g. opsonized zymosan, formyl-methionyl-leucyl phenylalanine, platelet activating factor, phorbol myristate acetate, and calcium ionophore A23187. The serine protease inhibitors TPCK and TLCK, and thiol protease inhibitor PHMB, diminished the CL with different potencies and in a dose dependent manner after treatment of cells with the various stimuli. Non-specific serine protease inhibitor, PMSF, and trypsin substrate TAME, showed a low inhibitory potency with respect to CL generation. Synthetic substrates for chymotrypsin (BTEE, ATEE) significantly inhibited CL with the various stimuli used with some differences in susceptibility to their inhibition. Specific chymotrypsin inhibitors diminished both the resting and activator-induced CL. We suggest that cell-bound chymotrypsin-like protease(s) is involved in the activation of signal transduction in human neutrophils after both receptor dependent and receptor-independent stimulation. PMID- 1642141 TI - Relationship between bone mass and rates of bone change at appendicular measurement sites. AB - The rate of bone change among postmenopausal women may vary depending upon the initial bone mass. Examining this possibility is difficult, however, because of a negative statistical bias that occurs when change is regressed against the initial value of the same variable. In this article, four statistical methods were applied to measure the association between bone mass and the rate of bone change. The study population was Japanese-American women, who were monitored for approximately 5 years. Bone changes were determined for the calcaneus and the distal and proximal radius. The results were consistent across the bone sites but differed between statistical methods. Three of the four methods indicated that the women with the greater bone mass had the greater loss rates. The fourth method did not support this association. Possible reasons for the discordant results are discussed. Using the "best" estimate of the relationship, a gradual convergence of bone mass was projected over time toward the population mean. The convergence occurred because women with higher bone mass had a somewhat faster loss rate than women with lower bone mass. Overall, however, the variation in bone mass between individuals was large compared to the rate of convergence. PMID- 1642142 TI - Factors influencing synthesis and mineralization of bone matrix from fetal bovine bone cells grown in vitro. AB - This study of the in vitro synthesis and mineralization of bovine bone demonstrates that sheets of mineralized matrix can be produced consistently within 18-24 days of cell isolation. Mineralization surpasses that achieved by other systems with other species: The deposition of mineral extends beyond nodules to form branching trabeculae and then solid wafers of bone. Comparison of the fetal age of the bone source, enzyme digestion methods, seeding density, culture surface, nutritive media, and concentration of fetal calf serum and other additives, including insulin and ascorbic acid, has yielded a set of optimal culture conditions. In the presence of ascorbic acid and beta-glycerol phosphate, insulin has a dose-dependent effect on the morphology of the mineralized bone matrix produced. Quantitative analysis shows that in these cultures calcium accumulates most rapidly between days 6 and 10 after the introduction of mineralization medium but that mineral accretion continues throughout 14-16 days of culture. Alkaline phosphatase levels rise up to 200-fold, concomitant with a rapid increase in the number of cells per culture during the early mineralization phases; both fall as mineralization proceeds. This system has been used to study the induction of mRNA of type I collagen, alkaline phosphatase, and several noncollagenous bone proteins during the course of mineralization. Because of the degree of mineralization achieved with this system, it has many potential applications. PMID- 1642143 TI - Bone matrix mRNA expression in differentiating fetal bovine osteoblasts. AB - In the accompanying study, we report an in vitro culture system from bovine bone cells that can be applied to investigate bone cell growth and differentiation. In this system, bovine bone cells placed in mineralization medium formed multilayers (days 2-3), began deposition of mineral (days 5-6), and eventually acquired a mineralized matrix sheet (days 14-20) through the stages of mineralizing nodules and trabecular-like structure. In the current study we used this system to investigate the relative expression of bone matrix genes that may play an important role in bone development and metabolism. alpha 1(I)-collagen, alkaline phosphatase, osteonectin, biglycan (PgI), decorin (PgII), osteopontin, and bone sialoprotein mRNA gene expression were measured on days 0, 2, 6, 10, and 20 (date when the cells were placed in mineralization medium as day 0). Total RNA was purified and analyzed by northern blot using radiolabeled cDNA encoding these genes. To comprehend the relationship between gene expression and mineralization, total calcium content in the cultures was also measured. During the culture period we observed several very different gene expression profiles. The expression of both alpha 1(I)-collagen and biglycan increased 3- to 4-fold by day 6 and then returned to basal levels by day 20. The osteonectin gene was highly expressed throughout the culture, with no significant increase in induction found during any time of culture. A significant induction of alkaline phosphatase (13.8 fold) gene expression was observed by day 6. Osteopontin showed a similar profile to that of alkaline phosphatase but had a much greater level of relative expression (26-fold) compared to day 0. Interestingly, downregulation during mineral accumulation seemed a common occurrence among many of the genes measured. In contrast, the bone sialoprotein gene showed a significant and distinct expression pattern, increasing rapidly after the onset of mineralization on day 6 and ultimately reaching 140-fold that of day 0. Decorin (Pg II) showed an increasing pattern, with the final relative level of induction 5-fold on day 20. These data suggest that the development of the mature osteoblastic phenotype, complete with the ability to produce a thick mineralized matrix, requires the differential regulation of a series of genes and their gene products over the culture period. PMID- 1642144 TI - Bone mineral density in the proximal femur and hip fracture type in the elderly. AB - Bone mineral density (BMD) in the contralateral proximal femur in 100 female elderly patients with hip fracture and the 35 controls without hip fracture were investigated using dual-photon absorptiometry. The hip fracture patients were divided into intracapsular fracture (n = 53) and extracapsular fracture (n = 47) groups, and these two groups were further divided into five subgroups according to fracture site: intracapsular fracture type 1 (transcervical fracture, n = 29) and type 2 (subcapital fracture, n = 24); extracapsular fracture type 1 (intertrochanteric line fracture, n = 13), type 2 (pertrochanteric fracture, n = 28), and type 3 (combined type of pertrochanteric and subtrochanteric fracture, n = 6). The intracapsular fracture group showed BMD values similar to those of controls; the extracapsular fracture group showed significantly lower BMD values than controls. When these two were subclassified into five subgroups, different results were seen in terms of BMD value in the proximal femur and fracture types; intracapsular fracture type 1 showed BMD values equivalent to those of controls; on the other hand, type 2 showed significantly lower BMD value than controls, and the BMD distribution in the proximal femur among the extracapsular fracture subgroups 1-3 differed, although all of them showed significantly lower BMD values than controls. The degree of trauma causing the fractures was also assessed according to available anamnestic data, but no significant difference was found in trauma tendency between the intra- and the extracapsular fracture group or among the subgroups in each group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642145 TI - Effects of resistance and endurance exercise on bone mineral status of young women: a randomized exercise intervention trial. AB - A substantial body of cross-sectional data and a smaller number of intervention trials generally justify optimism that regular physical activity benefits the skeleton. We conducted an 8 month controlled exercise trial in a group of healthy college women (mean age = 19.9 years) who were randomly assigned to a control group or to progressive training in jogging or weight lifting. We measured the following variables: bone mineral density (BMD) of the spine (L2-4) and right proximal femur using dual-energy x-ray absorptiometry, dynamic muscle strength using the 1-RM method, and endurance performance using the 1.5 mile walk/run field test. A total of 31 women completed the 8 month study. For women completing the study, compliance, defined as the percentage of workout sessions attended, was 97% for the runners (range 90-100%) and 92% (range 88-100%) for the weight trainers. Body weight increased by approximately 2 kg in all groups (p less than 0.05). Weight training was associated with significant increases (p less than 0.01) in muscle strength in all muscle groups. Improvement ranged from 10% for the deep back to 54% for the leg. No significant changes in strength scores were observed in the control or running groups. Aerobic performance improved only in the running group (16%, p less than 0.01). Lumbar BMD increased (p less than 0.05) in both runners (1.3 +/- 1.6%) and weight trainers (1.2 +/- 1.8%). These results did not differ from each other but were both significantly greater than results in control subjects, in whom bone mineral did not change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642146 TI - Effects of heparin on osteoclast activity. AB - The effect of heparin on osteoclastic bone resorption was studied in vitro using the disaggregated osteoclast resorption assay. Bone resorption was assessed by counting the resorption lacunae on bone slices by light microscopy. Low concentrations of heparin (5 micrograms/ml) increased bone resorption by isolated chick and rat osteoclasts. Among other glycosaminoglycans tested at 5 micrograms/ml, only dextran sulfate showed a small but significant stimulation of resorption. Chondroitin sulfates A, B, and C were without effect at 25 and 100 micrograms/ml, whereas resorption was increased by 100 micrograms/ml of heparan sulfate. With chick osteoclasts, which could be maintained in serum-free conditions, a stimulatory effect of heparin was found both in the presence of 5% fetal calf serum and in serum-free media containing insulin, transferrin, and selenium. The magnitude of the heparin-induced increase in resorption was similar in the presence or absence of serum. The stimulation of resorption was associated with an increase in the number of osteoclasts on bone slices. Pretreatment of the bone slices with heparin also enhanced resorption. In time course experiments, 5 micrograms/ml of heparin caused a doubling of chick osteoclast activity index (number of resorption pits per number of osteoclasts) at 12 and 24 h. In 24 h cultures, treatment with 10 micrograms/ml of the arginine-rich basic protein, protamine, 1 microgram/ml of the immunosuppressant, cyclosporine A, or 5 micrograms/ml of the cysteine-proteinase inhibitor, leupeptin, negated the heparin effect on bone resorption. Leupeptin also inhibited basal resorption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642147 TI - Quantitation of skeletal alkaline phosphatase isoenzyme activity in canine serum. AB - Pursuing the hypothesis that quantitation of skeletal alkaline phosphatase (ALP) activity in canine serum would provide an index of the rate of bone formation, we compared three methods for isoenzyme-specific identification of skeletal ALP activity in canine serum: heat inactivation, wheat germ agglutinin (WGA) precipitation, and concanavalin A (ConA) precipitation. ALP isoenzyme activities were extracted from canine bone, intestine, and liver, diluted into heat inactivated canine serum (i.e., serum without ALP activity), and used as calibrators of ALP isoenzyme activities. Differential sensitivity to inhibition by 10 mM L-homoarginine was used to distinguish intestinal ALP activity from hepatic and skeletal ALP activities (i.e., 9, 80, and 72% inhibition, respectively). To allow resolution of skeletal ALP activity from hepatic ALP activity, we tested two established methods (heat inactivation and WGA precipitation) and a novel method, ConA precipitation. The organ-derived skeletal and hepatic ALP isoenzyme activities were used to compare these three methods with respect to linearity, isoenzyme separation, and precision. All three methods were linear, but the WGA and ConA methods afforded greater isoenzyme separation and precision. The relative extent of isoenzyme separation (i.e., the difference in percentage remaining skeletal and hepatic ALP isoenzyme activities) averaged 23, 40, and 47% remaining ALP activity for the heat, WGA, and ConA methods, respectively. However, when these methods were applied to the quantitation of skeletal ALP activity in sera from 10 young and 10 adult beagles, the WGA method was found to be unacceptable because most of the results fell outside the range of the WGA assay calibrators (i.e., greater than 100% skeletal ALP activity). The heat and ConA methods showed that the amount of skeletal ALP activity in the beagle sera decreased with age, both as ALP activity per liter and as percentage of total serum ALP activity (p less than 0.001 for each). Skeletal ALP activity levels determined by ConA were correlated with values determined by heat inactivation (r = 0.87, p less than 0.001) but not with WGA-determined levels (r = 0.26). Intestinal ALP activity was detected in only 1 of these 20 sera. We conclude that ConA precipitation can be used for quantitation of skeletal ALP activity in beagle serum. PMID- 1642148 TI - Expression of mutant alpha (I)-procollagen in osteoblast and fibroblast cultures from a proband with osteogenesis imperfecta type IV. AB - This study compares the synthesis of mutant type I collagen in cultured dermal fibroblasts and trabecular osteoblasts that were isolated from a patient with moderately severe osteogenesis imperfecta (type IV). Previous study of this patient's dermal fibroblasts revealed a 2000 dalton deletion located in cyanogen bromide peptide 4 of alpha 2(I)-collagen. The phenotype of the bone cell cultures was defined by a 3-4 day logarithmic phase doubling time, predominantly type I collagen production over type III and alkaline phosphatase activity 13.5 times dermal fibroblast levels. The current study revealed that both fibroblasts and osteoblasts synthesized a normal and a shortened alpha 2(I) chain, each as the product of separate alleles. Following pepsin treatment of the procollagens, a shortened alpha 1(I) chain was also seen in both cell types. Cyanogen bromide peptide mapping of osteoblast alpha-chains demonstrated the same deletions in the cyanogen bromide peptide 4 as observed in the fibroblast cyanogen bromide maps. PAGE analysis of oligonucleotide-specific cDNA that was reverse transcribed from RNA isolated from fibroblasts and osteoblasts also demonstrated the presence of two bands, one the normal size of alpha 2(I) cDNA and a second species that was smaller by 54 base pairs. Sequencing of polymerase chain reaction-amplified cDNA fragments revealed an in-frame deletion of exon 12. This finding was confirmed by the RNase protection method. Genomic DNA sequencing detected a T----G point mutation in the second position of the 5' splice donor site of intron 12. Therefore, in this patient with osteogenesis imperfecta there was no qualitative alteration in the osteoblast-specific expression of this mutant alpha 2(I) collagen allele compared to dermal fibroblasts. PMID- 1642149 TI - Impact of short-term estrogen administration on growth hormone secretion and action: distinct route-dependent effects on connective and bone tissue metabolism. AB - We recently reported that estrogen exerts distinct effects on the GH/IGF-1 axis that are dependent on the route of delivery, probably reflecting a first-pass effect on hepatic IGF-1 production. Oral administration reduces IGF-1 and increases GH levels; transdermal administration elevates IGF-1 without changing GH concentrations. Since mesenchymal tissue is a target for GH and IGF-1 action, we studied changes in the GH/IGF-1 axis following oral (ethinyl estradiol, 20 micrograms/day) versus transdermal (Estraderm 100 TTS, Ciba Geigy, 100 micrograms 17 beta-estradiol per day) estrogen delivery and compared corresponding effects on connective and bone tissue metabolism. Mean 24 h GH levels, IGF-1, markers of fibroblast (procollagen III) and osteoblast (procollagen I, osteocalcin) function, and indices of bone turnover (fasting urinary hydroxyproline and calcium to creatinine ratios, UOHPr/Cr and UCa/Cr) were measured before and after 2 months of either oral or transdermal therapy in two groups of postmenopausal women. Transdermal estrogen administration significantly (p less than 0.05) increased IGF-1, procollagen III, procollagen I, osteocalcin, and UOHPr/Cr. In contrast, oral estrogen administration had a suppressive effect; the levels of IGF-1 (p = 0.001), procollagen III (p = 0.018), procollagen I (p = 0.002), osteocalcin (p = 0.015), and UOHPr/Cr (p = 0.004) were significantly different from those measured during transdermal administration. Both treatments significantly reduced UCa/Cr (p less than 0.015). IGF-1 changes during estrogen therapy were significantly related (p less than 0.05) to changes in procollagen III, procollagen I, osteocalcin, and UOHPr/Cr. Transdermally delivered estrogen stimulates IGF-1 production, increases osteoblastic function, and stimulates bone and nonbone collagen synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642150 TI - Detection of canine distemper virus in bone cells in the metaphyses of distemper infected dogs. AB - In the light of recent evidence implicating canine distemper virus (CDV) as a possible etiologic agent in Paget's disease of bone, we thought that it would be of interest to examine distemper-infected bone in the natural host. Samples from the long bones, spleen, and bladder of four distemper-infected and three uninfected dogs were examined for the presence of CDV nucleocapsid and phosphoprotein genes and the measles virus (MV) nucleocapsid gene using the technique of in situ hybridization with radioactively labeled riboprobes. Two of the four distemper-infected dogs showed strongly positive hybridization with both of the CDV probes. The signal was present in marrow cells, in osteoblasts, in osteocytes, and particularly in osteoclasts. No hybridization was seen over the cartilage cells of the growth plate, and there was a clear line of demarcation at the point of invasion of osteoclasts and vascularization. The spleen and bladder samples from infected dogs also showed positive hybridization. There was no hybridization with the MV probe in any of the distemper-infected tissue. Samples from the uninfected dogs showed no evidence of hybridization with either the CDV or MV probes. These results show that CDV can infect bone cells of the natural host and provide further support for the theory that CDV may play a role in human Paget's disease of bone. PMID- 1642151 TI - Suppression of PTH and decreased action on bone are partially responsible for the low calcemic activity of 22-oxacalcitriol relative to 1,25-(OH)2D3. AB - We previously showed that OCT, an analog of 1,25-(OH)2D3 with little calcemic activity, can decrease PTH mRNA levels in normal rats and inhibit PTH secretion in cultured bovine parathyroid cells with the same potency as 1,25-(OH)2D3 and that in normal rats fed a normal calcium diet, administration of OCT (500 ng) for 5 days did not increase plasma Ca. Thus, to determine if PTH suppression by OCT contributes to its lack of calcemic activity and to further characterize the effects of OCT on Ca metabolism, we performed several studies in parathyroidectomized (PTX) rats. PTX rats, maintained on a normal diet (0.9% Ca), received daily injections of vehicle, 1,25-(OH)2D3 (200 ng/day), or OCT (200 ng/day) for 6 days. Plasma Ca was measured daily. Plasma Ca in control rats stayed between 6.60 and 7.40 mg/dl, whereas Ca increased to 12.9 +/- 0.42 mg/dl in 1,25-(OH)2D3-treated rats and to 9.53 +/- 0.35 mg/dl in OCT-treated rats after 6 days. With a Ca-deficient diet, control rats maintained a plasma Ca between 4.25 and 4.60 mg/dl, but Ca increased to 13.7 +/- 0.24 mg/dl with 1,25-(OH)2D3 and to 7.29 +/- 0.17 mg/dl with OCT. Since the elevation in Ca by OCT was similar with both diets, OCT appears to act primarily on bone. PTX rats were infused with PTH (1.84 micrograms/kg/day) via an Alzet pump to achieve normal plasma Ca and then treated daily with either vehicle or OCT (200 ng/day). After 6 days, OCT increased serum Ca to 10.7 +/- 0.21 mg/dl over a control value of 8.58 +/- 0.29 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642152 TI - Dual-energy x-ray absorptiometry of the forearm: reproducibility and correlation with single-photon absorptiometry. AB - Although single-photon absorptiometry (SPA) has been the predominant tool used to assess bone mineral density (BMD) in the forearm, the development of dual-energy x-ray absorptiometry (DEXA) provides the benefits of greater source stability, reduced scanning time, and improved image resolution compared to SPA. In the present study we used the DEXA bone densitometer (Hologic, Inc., Waltham, MA) to (1) measure BMD in the one-third radius and ultradistal radius; (2) examine the reproducibility of these BMD measurements; and (3) compare the BMD at the one third radius with SPA (SP2, Lunar Corp., Madison, WI). In 65 normal women (ages 22-74 years) we examined changes in the forearm DEXA BMD with age, revealing significant quadratic regression equations. The reproducibility of DEXA BMD (mean +/- SEM) in 7 normal subjects aged 22-50 years is 0.85 +/- 0.16% for the predominantly cortical one-third radius site and 0.97 +/- 0.15% for the more trabecular ultradistal site. The regression relationship between DEXA and SPA of the one-third radius in 26 subjects (ages 22-68 years) is DEXA BMD = 0.105 + 0.826 (SPA BMD); R = 0.97, R2 = 0.94, p less than 0.0001. Bone densitometry of the forearm using DEXA may be performed relatively rapidly, providing reproducibility and image resolution that are generally superior to those observed with SPA. PMID- 1642154 TI - Microbial degradation of nitroaromatic compounds. PMID- 1642153 TI - Expression of human transforming growth factor alpha by Chinese hamster ovarian tumors in nude mice causes hypercalcemia and increased osteoclastic bone resorption. AB - Transforming growth factor alpha (TGF-alpha) is a polypeptide regulator of cell growth produced by many malignant tumors. It stimulates osteoclastic resorption in bone organ culture and osteoclast-like cell formation in marrow culture. To determine whether tumor production of TGF-alpha can cause hypercalcemia in vivo, we used Chinese hamster ovarian (CHO) cells transfected with the human TGF-alpha gene (TCHO), which stably express and secrete TGF-alpha. We used nontransfected CHO cells as controls (CCHO). TCHO and CCHO were inoculated intramuscularly into one hindlimb of nude mice and grew as local solid tumors. After 4 weeks of TCHO tumor growth, plasma ionized calcium (Ca2+) increased to reach 1.48 +/- 0.03 mM (mean +/- SEM), whereas mice bearing similarly sized CCHO tumors and non-tumor bearing mice (NTB) remained normocalcemic (normal range for Ca2+, 1.15-1.30 mM). Plasma TGF-alpha was undetectable by an ELIFA assay in all NTB mice, was markedly increased in all TCHO mice (5.75 +/- 0.78 ng/ml), and was slightly increased in CCHO mice (0.50 +/- 0.22 ng/ml). Quantitative bone histomorphometry showed a prominent increase in osteoclastic bone resorption in TCHO mice. These data suggest that TGF-alpha is a mediator of hypercalcemia and increased osteoclastic bone resorption in tumors that produce it in sufficient quantity. PMID- 1642155 TI - Medicinal benefits of the mushroom Ganoderma. PMID- 1642156 TI - Microbial degradation of biphenyl and its derivatives. PMID- 1642157 TI - An evaluation of bacterial standards and disinfection practices used for the assessment and treatment of stormwater. PMID- 1642158 TI - Biopotentialities of the basidiomacromycetes. PMID- 1642160 TI - Complete prescription orders reduce medication errors. PMID- 1642159 TI - Pharmacist with AIDS wins right to practice. PMID- 1642161 TI - Ancient antidote ignored. PMID- 1642162 TI - Inside a poison center. PMID- 1642164 TI - Create value-added services to meet patient needs. PMID- 1642163 TI - The tuberculosis epidemic and the pharmacist's role. PMID- 1642166 TI - Expiration dating. PMID- 1642165 TI - The effect of new clinical lab rules on your pharmacy. PMID- 1642167 TI - Design and evaluation of a solid sampler for the monitoring of airborne 1,6 hexamethylene diisocyanate (HDI) and its prepolymers in two-component spray painting. AB - An active, solvent-free solid sampler was developed for the collection of 1,6 hexamethylene diisocyanate (HDI) aerosol and prepolymers. The sampler was made of a filter impregnated with 1-(2-methoxyphenyl)piperazine contained in a filter holder. Interferences with HDI were observed when a set of cellulose acetate filters and a polystyrene filter holder were used; a glass fiber filter and polypropylene filter cassette gave better results. The applicability of the sampling and analytical procedure was validated with a test chamber, constructed for the dynamic generation of HDI aerosol and prepolymers in commercial two component spray paints (Desmodur N75) used in car refinishing. The particle size distribution, temporal stability, and spatial uniformity of the simulated aerosol were established in order to test the sampler. The monitoring of aerosol concentrations was conducted with the solid sampler paired to the reference impinger technique (impinger flasks contained 10 mL of 0.5 mg/mL 1-(2 methoxyphenyl)piperazine in toluene) under a controlled atmosphere in the test chamber. Analyses of derivatized HDI and prepolymers were carried out by using high-performance liquid chromatography and ultraviolet detection. The correlation between the solvent-free and the impinger techniques appeared fairly good (Y = 0.979X-0.161; R = 0.978), when the tests were conducted in the range of 0.1 to 10 times the threshold limit value (TLV) for HDI monomer and up to 60 micrograms/m3 (3 U.K. TLVs) for total -N=C=O groups. PMID- 1642168 TI - The acute toxicity evaluation of a low-temperature hydraulic fluid. AB - A low-temperature version of MIL-H-83282 (LT 83282) is a candidate hydraulic fluid to be used as a replacement for the current low-temperature fluid used on Strategic Air Command aircraft. A single neat dose of 0.1 mL LT 83282 into New Zealand White (NZW) rabbit eyes resulted in slight conjunctival irritation for up to 24 hr after treatment in two of nine rabbits. Rinsing the eyes after treatment appeared beneficial. A single treatment of 0.5 mL neat LT 83282 to rabbit skin produced no irritation. A total of 40% of the guinea pigs receiving repeated dermal application of the fluid demonstrated a positive sensitization response. A single oral dose of 5 g LT 83282/kg body weight given to five male and five female Fischer 344 (F-344) rats and a single dermal application of 2 g LT 83282/kg body weight applied to five male and five female NZW rabbits resulted in no deaths. Inhalation exposures to aerosol concentrations of LT 83282 resulted in an LC50 of 2.13 and 1.50 mg/L for male and female F-344 rats, respectively. No clinical signs of acute delayed neurotoxicity were observed in hens twice dosed at limit levels (5 g/kg) and observed for 21 days. PMID- 1642169 TI - Subchronic rat inhalation study with Skydrol 500B-4 fire resistant hydraulic fluid. AB - Skydrol 500B-4 fire resistant hydraulic fluid, a proprietary phosphate ester mixture composed principally of dibutyl phenyl phosphate (DBPP) and tributyl phosphate (TBP) and used as a commercial airline hydraulic fluid, was evaluated in an inhalation toxicity study of Sprague-Dawley rats. Target exposure levels used in the study were 0, 5, 100, and 300 mg/m3, and exposures were maintained for 6 hr/day, 5 days/week. Mass median aerodynamic diameters determined for particles in the mid- and high-exposure inhalation chambers were 2.85 microns and 3.31 microns, with geometric standard deviations of 1.99 microns and 1.92 microns, respectively. The percentage of particles less than 10 microns in diameter were 96.4% in the mid-exposure chamber and 95.5% in the high-exposure chamber. After 6 weeks of Skydrol exposure, 10 rats/sex/group were euthanized and then assessed for indications of possible chemical toxicity. Another 15 rats/sex/group were studied for a total of 13 weeks of exposure. The only clinical sign of chemical toxicity was the observation of a reddish nasal discharge with accompanying oral salivation in mid- and high-exposure animals of both sexes, indicative of an irritant response. Statistically significant reduced body weights; increased absolute and relative liver weights; and decreased erythrocyte counts, hemoglobin levels, and hematocrit values were observed in high-exposure female rats euthanized after 13 weeks of Skydrol exposure. High exposure male rats also had increased absolute and relative liver weights and decreased hematocrit values after 13 weeks. Plasma cholinesterase levels were decreased in high-exposure female rats both 6 and 13 weeks after the study was initiated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642170 TI - Inhalation of diethylamine--acute nasal effects and subjective response. AB - Adult volunteers were exposed to 25 ppm (75 mg/m3) diethylamine in a climate chamber for 15 min in order to study the acute nasal reactions to an exposure equivalent to the present threshold limit value-short-term exposure limit. Changes in nasal volume and nasal resistance were measured by acoustic rhinometry and by rhinomanometry. Acute change in nasal volume, usually seen as acute nasal mucosa response to thermal stimuli, was not observed, nor was an acute change in nasal airway resistance. In a subsequent experiment, the aim was to measure acute sensory effects. Exposure to a concentration increasing from 0 to 12 ppm took place for 60 min, equal to an average concentration of 10 ppm (30 mg/m3). A moderate to strong olfactory response and distinct nasal and eye irritation were observed. In spite of considerable individual variation, the results were in agreement with sensory effect estimates obtained from animal studies. PMID- 1642171 TI - Cobalt exposure in a carbide tip grinding process. AB - Reports relating hard metal disease or nonspecific respiratory symptoms to tungsten or cobalt exposure have been published in the past 20 yr. This report discusses a work site investigation of a small company, employing approximately 50 workers, producing carbide tip saw blades for the woodworking industry. Cobalt exposure was characterized by ambient air monitoring (area and personnel), particle size determination, and biological monitoring. Area sampling for cadmium, cobalt, and tungsten indicated low ambient air levels in all manufacturing areas except the grinding department, which had cobalt air levels approaching the threshold limit value of 0.05 mg/m3. Area airborne cobalt exposure levels measured over six shifts in the grinding department ranged from 0.017 to 0.12 mg/m3 for the total collection method and 0.002 to 0.028 mg/m3 for the method collecting respirable particles. Cobalt content in the total and respirable fractions was similar. Urine monitoring indicated production workers have elevated cobalt levels, and the grinders' levels were higher than other production workers. The grinding coolant was found to have elevated cobalt concentrations. A survey of coolants from nine carbide grinding shops indicated the elevated cobalt concentrations may be common. PMID- 1642172 TI - Respirator performance rating table for mask design. AB - The ultimate goal for respirator mask designers is computer-aided design. Mask design, however, is a very complex operation, with many different interrelationships. Current knowledge does not allow significant incorporation of physiological information into mask design. Rather, physiological information is usually gathered during mask evaluation, after the design process has been completed. The Performance Rating Table (PRT) is a beginning step to formulating physiological knowledge in a way that can be useful for design. The PRT organizes physiological knowledge to assign performance data to various mask and level of work causes. Best estimates of tabled values were obtained from the literature. PMID- 1642173 TI - Exposure of hospital operating room personnel to potentially harmful environmental agents. AB - Epidemiologic studies of risk to reproductive health arising from the operating room environment have been inconclusive and lack quantitative exposure information. This study was undertaken to quantify exposure of operating room (OR) personnel to anesthetic agents, x-radiation, methyl methacrylate, and ethylene oxide and to determine how exposure varies with different operating room factors. Exposures of anesthetists and nurses to these agents were determined in selected operating rooms over three consecutive days. Each subject was asked to wear an x-radiation dosimeter for 1 month. Exposure to anesthetic agents was found to be influenced by the age of the OR facility, type of surgical service, number of procedures carried out during the day, type of anesthetic circuitry, and method of anesthesia delivery. Anesthetists were found to have significantly greater exposures than OR nurses. Exposure of OR personnel to ethylene oxide, methyl methacrylate, and x-radiation were well within existing standards. Exposure of anesthetists and nurses to anesthetic agents, at times, was in excess of Ontario exposure guidelines, despite improvements in the control of anesthetic pollution. PMID- 1642174 TI - Evaluation of OSHA method 5 for measuring chloroform in pulp and paper industry workplace and ambient atmospheres. AB - As a result of the recent lowering of the Occupational Safety and Health Administration's (OSHA's) permissible exposure limit (PEL) for chloroform from 50 ppm to 2 ppm, interest has increased in measuring chloroform in pulp and paper industry workplace atmospheres. OSHA suggested that its Method 5 should be used for measuring chloroform concentrations in the range of the new PEL. There are some potential problems with using Method 5 for this purpose. Pulp and paper industry atmospheres may interfere with the measurement because of high temperature, high humidity, and the presence of chlorine. The charcoal sorbent tubes specified in OSHA Method 5 were challenged in the laboratory with a test gas containing 0.1, 0.5, 1, and 2 times the PEL of chloroform at 38 degrees C with 80% to 93% relative humidity and ca. 0.5 ppm chlorine. Application of the National Institute for Occupational Safety and Health (NIOSH) validation protocol to the results indicated a bias of -8.2% and a pooled coefficient of variation (CV) of 0.0274. The method CV is less than the critical CV; thus, the method is acceptable by the NIOSH validation protocol under these conditions. Field testing of OSHA Method 5 was successful and did not reveal any unexpected problems. Additional tests showed that with some modification, OSHA Method 5 can be used to measure chloroform concentrations in ambient atmospheres down to 0.1 ppb. PMID- 1642175 TI - Limitations of ambient air quality standards in evaluating indoor environments. AB - Analysis of the kinds of data used for the derivation of ambient air quality standards (AAQSs) for carbon monoxide and ozone shows that these values are based on the toxicology of the materials and thus are suitable for evaluating potential health effects of indoor environments, especially on the very young, the aged, and the infirm. A similar analysis shows that the AAQSs for suspended particulate matter, nitrogen dioxide, and sulfur dioxide are strictly empirical and that they should not be used for any but their first, intended purpose. The AAQSs for non methane hydrocarbons are based on photochemical smog production, not injury of any kind, and have no utility for indoor environment evaluation. PMID- 1642176 TI - Efficiency of a physician-operated mobile intensive care unit for prehospital thrombolysis in acute myocardial infarction. AB - The efficiency of an emergency medical system for routinely performed prehospital thrombolysis is evaluated for 1 of the 7 physician-staffed mobile intensive care units (MICU) in former West Berlin. During 19 consecutive months the MICU had 4,920 missions, and 1,226 patients had chest pain of presumed cardiac origin. The diagnosis at hospital discharge was acute myocardial infarction (AMI) in 406 patients and "interrupted" infarction in 11 patients (total 417). Correct on scene electrocardiographic diagnosis of acute injury was made in 268 patients (64%) and was false-positive in 4 patients (1%). In 8%, present ST elevations were not recognized. In 27%, the electrocardiogram on scene was nondiagnostic (16% with no ST elevation, 11% with bundle branch block). Of all 417 patients with later hospital evidence of AMI, 317 (76%) were seen by the MICU physician within 4 hours, and 173 (41%) within the first hour from symptom onset. Two hundred three patients seen within 4 hours had diagnostic ST elevation on the scene, of whom 124 (61%) received prehospital thrombolysis (74 patients [36%] within the first hour). There was no prehospital death; hospital mortality was 6.3%. Because greater than 50% of all patients in the community, hospitalized because of AMI, made use of the MICU and 3/4 of them had called within 4 hours from symptom onset, a large proportion of all patients with AMI were candidates for the actually received prehospital thrombolysis. PMID- 1642177 TI - Patient delay and receipt of thrombolytic therapy among patients with acute myocardial infarction from a community-wide perspective. AB - The duration of patient delay from the time of onset of symptoms of acute myocardial infarction (AMI) to hospital presentation, and the relation of delay time and various patient characteristics to receipt of thrombolytic therapy were examined as part of a community-based study of patients hospitalized with AMI in the Worcester, Massachusetts, metropolitan area. In all, 800 patients with validated AMI hospitalized at 16 hospitals in the Worcester metropolitan area in 1986 and 1988 constituted the study sample. Patients delayed on average 4 hours between noting symptoms suggestive of AMI and presenting to area-wide emergency departments with no significant change observed between 1986 and 1988. The shorter the time interval of delay, the greater the likelihood of receiving thrombolytic therapy; patients arriving at the emergency department within 1 hour of the onset of acute symptoms were approximately 2.5 and 6.5 times more likely to receive thrombolytic agents than were those presenting to the hospital between 4 and 6, and greater than 6 hours, respectively, after the onset of symptoms. Results of a multivariate analysis showed increasing length of delay, older age, history of hypertension or AMI and non-Q-wave AMI to be significantly associated with failure to receive thrombolytic therapy. PMID- 1642178 TI - Diagnosis of right ventricular acute myocardial infarction by dual isotope thallium-201 and indium-111 antimyosin SPECT imaging. AB - To assess the diagnostic value of indium-111 antimyosin for detecting right ventricular (RV) wall acute infarction, 30 patients with electrocardiographic documented left ventricular inferior (posterior) wall acute myocardial infarction underwent simultaneous dual isotope indium-111 antimyosin and thallium-201 single photon emission computed tomography (SPECT) within 2 days of admission. RV necrosis was defined as uptake of indium-111 antimyosin anterior and to the right of septal thallium uptake. Twenty-nine of the 30 patients (97%) had indium-111 antimyosin uptake in the inferior, posterior or lateral walls of the left ventricle and 14 of 30 (47%) had additional RV antimyosin uptake. Three different patterns of RV uptake of indium-111 antimyosin were observed: crescent-shaped, focal and apical. Twenty-seven patients underwent gated blood pool scanning before hospital discharge. Twelve of the 14 patients with RV antimyosin uptake had gated blood pool scintigraphy and 7 of 12 had RV dysfunction; 5 had normal RV function. Except for 1 patient who had questionable RV antimyosin uptake and had RV dysfunction, no patient without RV antimyosin uptake had RV dysfunction. In summary, right and left ventricular necrosis can be detected on tomographic images of indium-111 antimyosin uptake in patients with inferior infarctions when simultaneous uptake of a perfusion tracer, thallium-201, is imaged and used as an aid to reconstruction and anatomic localization. PMID- 1642179 TI - Frequency of late potentials on signal-averaged electrocardiograms during thallium stress testing in coronary artery disease. AB - Late potentials detected by signal-averaged electrocardiography (SAECG) are an important noninvasive indicator identifying patients with previous myocardial infarction at risk for developing ventricular tachycardia. The role of myocardial ischemia in the development of late potentials is undefined. This study attempts to determine if late potentials on SAECG can be produced during scintigraphically proven ischemia. A signal-averaged electrocardiogram was obtained before and immediately after single-photon emission computed tomography thallium exercise testing in 51 patients. Reversible ischemia was documented in 25 cases with no significant changes in the parameters of SAECG; patients with previous myocardial infarction (n = 10) also had no significant changes from baseline. Multivariate analysis with respect to reversible ischemia and previous myocardial infarction was unrevealing. Patients with late potentials at baseline (n = 10) who developed reversible ischemia (n = 5) had a shorter QRS duration than those with late potentials at baseline and no reversible ischemia. The data indicate that exercise-induced scintigraphically proven ischemia does not alter SAECG even in the presence of previous myocardial infarction. Patients with late potentials at baseline may actually have a shortened QRS duration during reversible ischemia as opposed to the expected lengthening of the QRS. PMID- 1642180 TI - Relation of the level of high-density lipoprotein subfractions to the presence and extent of coronary artery disease. AB - Plasma lipid profiles, including high-density lipoprotein (HDL) subfractions HDL2 and HDL3, were obtained in 115 men undergoing coronary angiography to assess the relation of lipid levels to coronary artery disease (CAD). CAD was present in 87 patients (76%) and absent in 28 (24%). The largest difference between the 2 groups were observed for HDL2 cholesterol, with a mean of 0.13 mmol/liter (5 mg/dl) in patients with CAD compared with 0.25 mmol/liter (10 mg/dl) in those without CAD (p less than 0.005). Smaller differences were found for HDL3 (1.02 mmol/liter [39 mg/dl] vs 1.19 mmol/liter [46 mg/dl]; p less than 0.005) and HDL (1.15 vs 1.42 mmol/liter [45 vs 55 mg/dl]; p less than 0.001) cholesterol, and apolipoprotein A-1 (1.37 vs 1.50 g/liter; p less than 0.01) and plasma triglycerides (1.79 vs 1.38 mmol/liter [159 vs 122 mg/dl]; p less than 0.05). No significant difference was found for plasma and low-density lipoprotein cholesterol, and apolipoprotein B levels. Simple regression analysis revealed that the most powerful independent variable associated with the extent of CAD was HDL2 cholesterol (Spearman rho = 0.311; p less than 0.001). Stepwise multiple regression analysis proved HDL2 cholesterol and age to be the strongest predictors of extent of CAD. The level of HDL2 cholesterol was reasonably well correlated with HDL cholesterol (r2 = 0.6; p less than 0.0001), but less so with plasma apolipoprotein A-1 (r2 = 0.4; p less than 0.0001). The data add to the growing body of information demonstrating an important association of HDL (and more specifically HDL2) with CAD in men. PMID- 1642182 TI - Intravascular ultrasound to assess aortocoronary venous bypass grafts in vivo. AB - In 20 consecutive patients (18 men and 2 women, aged 42 to 72 years) undergoing repeat coronary angiography because of new onset of angina pectoris 4 months to 11 years (mean 53 months) after aortocoronary saphenous venous bypass operation, the graft to the left anterior descending (n = 12), left circumflex (n = 4) or right coronary (n = 2) artery, or a diagonal branch (n = 2) was studied by both intravascular ultrasound and angiography. Sonographic images were obtained using a 4.8Fr catheter with a crystal mechanically rotated at 900 rpm; quantitative coronary angiograms were recorded in biplane projections. In 18 patients, qualitatively as well as quantitatively evaluable images could be recorded; no complications occurred. The venous wall in general appeared to be homogenous; there were no separate layers identifiable. Simultaneous ultrasound and angiographic measurements were performed at a total of 75 sites (2 to 6 per bypass). In 4 of these patients (10 of 75 sites), neither intravascular ultrasound nor angiography revealed any pathologic changes; these bypasses were classified as normal. At the remaining 65 sites, arteriosclerotic lesions were detected in each case by ultrasound, but at only 33 sites by angiography. Median wall thickness was 0.59 mm (95% confidence interval 0.54 to 0.63) in normal grafts and 1.02 mm (0.99 to 1.07; p less than 0.001) in diseased grafts. The cross-sectional luminal area determined by ultrasound correlated well with the angiographic assessment (r = 0.90; p less than 0.001), but the measured values were significantly higher (17 +/- 4 vs 14 +/- 4 mm2; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642181 TI - Comparison of heart rate variability in survivors and nonsurvivors of sudden cardiac arrest. AB - Imbalances in autonomic nervous system function have been posed as a possible mechanism that produces ventricular fibrillation and sudden cardiac arrest in patients with cardiovascular disease. Heart rate (HR) variability is described in survivors and nonsurvivors of sudden cardiac arrest within 48 hours after resuscitation using time and frequency domain analytic approaches. HR data were collected using 24-hour ambulatory electro-cardiograms in 16 survivors and 5 nonsurvivors of sudden cardiac arrest, and 5 control subjects. Survivors of sudden cardiac arrest were followed for 1 year, with recurrent cardiac events occurring in 4 patients who died within that year. Analysis of 24-hour electrocardiograms demonstrated that control subjects had the highest HR variability (standard deviation of all RR intervals = 155.2 +/- 54 ms), with nonsurvivors demonstrating the lowest HR variability (standard deviation of all RR intervals = 52.3 +/- 6.1 ms) and survivors of sudden cardiac arrest falling between the other 2 groups (standard deviation of all RR intervals = 78 +/- 25.5 ms, p less than or equal to 0.0000). Two other indexes of HR variability (mean number of beat to beat differences in RR intervals greater than 50 ms/hour and root-mean-square of successive differences in RR intervals) did not demonstrate the expected pattern in this sample, indicating that perhaps patterns of HR variability differ between groups of patients with cardiovascular disorders. Spectral analytic methods demonstrated that survivors of sudden cardiac arrest had reduced low- and high-frequency spectral power, whereas nonsurvivors demonstrated a loss of both low- and high-frequency spectral power.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642183 TI - Ventricular tachycardia in Chagas' disease. AB - This study examined the usefulness of the electrophysiologic approach for selecting antiarrhythmic drug therapy to improve survival in patients with ventricular tachycardia (VT) and Chagas' disease. A total of 71 consecutive chagasic patients undergoing treatment and evaluation of VT were analyzed. Programmed electrical stimulation (PES) was performed in 45 patients, sustained VT was induced in 18 of these 45 (40%); nonsustained VT was induced in 17 (38%), and in 10 patients (22%) VT was not induced at all. An average of 3 drugs per patient were tested, including mexiletine, flecainide and propafenone. At least 1 effective drug preventing VT induction was identified in 13 of 18 patients with induced sustained VT, whose outcome resulted in 2 nonsudden but cardiac deaths (15%). Eight patients received no drug therapy because the induced arrhythmia was asymptomatic nonsustained VT; none of these died. The remaining 24 patients from the PES group were empirically treated with amiodarone; 7 died (4 suddenly) during follow-up (29%). A group of 26 patients (non-PES group) did not undergo electrophysiologic evaluation. In these patients, the therapy chosen was amiodarone alone or associated with mexiletine, and the incidence of death was 7 of 26 patients (27%), 3 suddenly (p less than 0.05 at 10-year survival and p = not significant at 5-year survival). It is concluded that the electrophysiologic approach improves survival in this study population, but only 29% were eligible for guided therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642184 TI - Comparison of atrial overdrive pacing with and without extrastimuli for termination of atrial flutter. AB - Atrial overdrive pacing has been successfully used to terminate atrial flutter. This study compared the efficacy of atrial extrastimuli following a rapid pacing train to overdrive pacing without atrial extrastimuli for the termination of atrial flutter. Patients were randomized to treatments of short or long burst atrial overdrive pacing or atrial overdrive pacing followed by atrial extrastimuli in a crossover study design. A total of 22 patients (73%) had successful conversion of atrial flutter to sinus rhythm. The success rates in patients exposed to each therapy, including crossover therapies, were 62% with the atrial extrastimuli method, 8% with the short burst pacing method, and 8% with the long burst pacing method (p less than 0.001). Transient atrial fibrillation developed in 15 patients and in 9 of these this arrhythmia preceded conversion to sinus rhythm. Sustained atrial fibrillation was induced in 3 additional patients but never with the atrial extrastimuli method. In conclusion, the method of delivering atrial extrastimuli after a rapid pacing train is highly efficacious for the termination of atrial flutter. Furthermore, this method is more effective than atrial overdrive pacing methods delivered at the same pacing cycle length. These observations have important implications for the programming of antitachycardia pacemakers. PMID- 1642185 TI - Effects of long-acting nifedipine on casual office blood pressure measurements, 24-hour ambulatory blood pressure profiles, exercise parameters and left ventricular mass and function in black patients with mild to moderate systemic hypertension. AB - Thirty-nine black patients with mild to moderate hypertension were treated for 1 year with various long-acting preparations of nifedipine, during which time serial changes in 24-hour ambulatory blood pressure (BP), exercise performance, left ventricular (LV) mass index and LV systolic function were evaluated. Mean 24 hour ambulatory BP decreased from 156 +/- 15/99 +/- 8 to 125 +/- 10/79 +/- 6 mm Hg at 1 year (p less than 0.0001). LV mass index decreased from 130 +/- 40 to 114 +/- 39 g/m2 at 6 weeks (p less than 0.005) and to 95 +/- 32 at 1 year (p less than 0.0001). There was a significant reduction in septal and posterior wall thickness from 11.0 +/- 2.0 to 9.3 +/- 2.0 mm (p less than 0.0001) and from 10.9 +/- 2.0 to 9.3 +/- 2.0 mm (p less than 0.005), respectively. Cardiac index and fractional shortening changed insignificantly from 2.9 +/- 0.7 to 2.9 +/- 0.6 liters/min/m2, and from 35 +/- 5 to 36 +/- 6%, respectively. At 1 year, using a modified Bruce protocol, exercise time increased from 691 +/- 138 to 845 +/- 183 seconds (p less than 0.05); peak exercise and 1 minute post-effort systolic BP decreased from 240 +/- 26 to 200 +/- 21 mm Hg and from 221 +/- 27 to 169 +/- 32 mm Hg (p less than 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642188 TI - Clinical significance of coronary artery disease in hypertrophic cardiomyopathy. AB - The role of coronary artery disease (CAD) in hypertrophic cardiomyopathy (HC) has not been thoroughly clarified. To assess the clinical and prognostic significance of these 2 coexistent diseases, 96 patients with HC (62 men, mean age 45 years) who underwent coronary arteriography and 2-dimensional echocardiography were studied. Significant stenosis (greater than 70%) of 1 or more coronary arteries was detected in 11 patients, all aged greater than 45 years. This group, compared with the other group without significant CAD (n = 85), was characterized by an older age (59 +/- 7 vs 42 +/- 15 years; p less than 0.05), a greater prevalence of previous myocardial infarction (24 vs 0%; p less than 0.001), complex ventricular arrhythmias (100 vs 50%; p less than 0.05), non-obstructive forms (82 vs 46%; p less than 0.05), dilated (45 vs 7%; p less than 0.02) and hypocontractile left ventricle (36 vs 6%; p less than 0.01) and higher mortality (36 vs 8%; p less than 0.05) during a mean follow-up of 3.6 years. It is concluded that CAD associated with HC is a complex clinical syndrome, difficult to diagnose clinically, that can reliably be recognized by coronary angiography. CAD seems to play an important role in modifying the pathophysiology, the natural history and the prognosis of HC. PMID- 1642186 TI - Renal function in severe congestive heart failure during treatment with enalapril (the Cooperative North Scandinavian Enalapril Survival Study [CONSENSUS] Trial). AB - The effect on renal function of long-term treatment with either enalapril (n = 123) or placebo (n = 120) in addition to conventional therapy was studied in a randomized trial in patients with severe congestive heart failure (New York Heart Association functional class IV; the Cooperative North Scandinavian Enalapril Survival Study). Enalapril was administered in a dose of 2.5 to 40 mg/day. The analysis was restricted to the first 6 months of treatment. There was an average initial increase of 10 to 15% (10 to 20 mumol/liter) irrespective of baseline serum creatinine within the first 3 weeks of enalapril treatment, whereafter mean serum creatinine remained on a similar level during the first 6 months. Enalapril was well-tolerated by most patients, and serum creatinine was reduced in 24%. Serum creatinine increased by greater than 100% in 13 patients (11%) in the enalapril group (mainly as a consequence of intercurrent disease or severe hypotension, and usually transiently) and in 4 (3%) in the placebo group. The maximal increase in serum creatinine in the enalapril group was inversely correlated to the diastolic blood pressure (p = 0.008) at baseline and to the mean diastolic and systolic blood pressures measured at the time of the maximal increase in serum creatinine (p = 0.0001). According to multivariate regression analysis, the maximal increase in serum creatinine was also slightly influenced by the dose of furosemide taken. The development of hypotension emerged as the strongest factor explaining an abnormal increase in serum creatinine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642187 TI - Detection of skeletal muscle fatigue in patients with heart failure using electromyography. AB - Patients with heart failure frequently report that leg fatigue limits maximal exercise capacity. However, objective documentation of muscle fatigue has not been obtained in such patients. In normal subjects, muscle fatigue during constant work load exercise is associated with an increase in electrical activity generated per contraction due to use of additional muscle fibers to compensate for fiber fatigue. The present study was performed to determine if this approach can be used to document muscle fatigue in patients with heart failure. Vastus lateralis surface electromyograms were monitored in 8 ambulatory patients with nonedematous heart failure and 6 normal subjects during maximal bicycle exercise (20 W increments every 2 minutes). The electromyogram was stored on tape and subsequently analyzed for integrated root-mean-square voltage/contraction (iRMSV). At each work load, the iRMSV of the first and last 30 seconds of the work load were compared. The maximal work load achieved by patients with heart failure was significantly lower (73 +/- 22 W) than that by normal subjects (150 +/- 15 W; p less than 0.01). Both groups had no significant difference between the initial and final iRMSV at submaximal work loads. However, during the 2 highest work loads, both groups reported leg fatigue and had significant increases in iRMSV, consistent with muscle fiber fatigue (maximal work load: 259 +/- 59 to 279 +/- 58 mv.ms [normals] vs 258 +/- 94 to 283 +/- 93 mv.ms [heart failure]; p less than 0.03). The data indicate that the surface electromyogram can be used to detect skeletal muscle fatigue in patients with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642189 TI - The "adult" form of the scimitar syndrome. AB - One hundred twenty-two cases of the adult form of the scimitar syndrome were collected from different cardiologic centers. The clinical, radiographic and hemodynamic findings are described. The scimitar syndrome is defined as an anomalous right pulmonary venous drainage, partial or complete, to the inferior vena cava. Additional characteristics of this syndrome such as hypoplasia and abnormalities of the vascular supply to the right lung, dextrocardia and abnormalities of the bronchial segmentation are common; bronchiectases are rare. The left to right shunt was less than 50% in 100 of the 122 patients. The pulmonary arterial pressures were normal in 94 patients and slightly elevated in 28. A follow-up study of these patients showed that, without surgical correction, they lead a normal life. An awareness of this syndrome may avoid unnecessary invasive diagnostic procedures and surgical treatment for most patients. PMID- 1642190 TI - Determinants of Doppler indexes of left ventricular diastolic function in normal subjects (the Framingham Heart Study). AB - Normative Doppler values and determinants of left ventricular (LV) diastolic function in healthy subjects have not been fully elucidated. Subjects from the Framingham Heart Study were examined to describe reference values and determinants of echocardiographic Doppler indexes of diastolic function. One hundred twenty-seven randomly selected, rigorously defined, normal subjects, approximately evenly distributed by sex and age from the third through the eighth decades were studied by Doppler echocardiography. Normative values for 7 frequently used Doppler indexes of LV diastolic function are presented. Doppler indexes of LV diastolic function change dramatically with age; the peak velocity of early filling divided by late filling (peak velocity E/A) ranges from a mean of 2.08 +/- 0.55 for subjects in their third decade to 0.84 +/- 0.29 for those in their eighth decade. A peak velocity E/A ratio less than 1 is abnormal in subjects aged less than 40 years, but occurs in most subjects aged greater than or equal to 70 years. The high correlations between age and Doppler indexes of LV diastolic function are not greatly attenuated after adjustment for other clinical parameters associated with diastolic function; the multivariate partial correlation coefficient between age and peak velocity E/A is -0.80 (p less than 0.0001). Heart rate, PR interval, LV systolic function, sex and systolic blood pressure are minor determinants of Doppler indexes of diastolic function. Body mass index, left atrial diameter, and LV wall thickness, internal dimension and mass have little or no association with Doppler indexes in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642191 TI - Frequency and significance of intrapulmonary right-to-left shunting in end-stage hepatic disease. AB - Intrapulmonary vascular abnormalities consisting of arteriovenous malformations and capillary dilatations have been described in patients with severe liver disease. These intrapulmonary vascular abnormalities can result in intrapulmonary right-to-left shunting and hypoxemia. Twenty-five of 53 patients (47%) with end stage hepatic disease were found to have contrast echocardiographic evidence of intrapulmonary right-to-left shunting. There was no difference in mean age, gender distribution, or severity of hepatic disease in those with and without evidence of such shunting. Although there was no difference in mean partial arterial oxygen pressure (PaO2) values in the 2 groups (82 +/- 11 vs 76 +/- 11 mm Hg), the mean PaO2 value of those with at least 2+ left ventricular opacification (2 to 4+) was significantly lower (66 +/- 3 mm Hg, n = 8; p less than 0.01). Unexpectedly, patients with evidence of intrapulmonary shunting had a lower mortality rate before transplantation (3 of 25, 12%) than those without evidence of shunting (10 of 28, 36%) resulting in a significant difference in actuarial survival (p less than 0.05) by the end of the follow-up period. It is concluded that intrapulmonary right-to-left shunting occurs frequently in patients with end stage liver disease and may be a marker of a positive biologic process that, in some way, leads to improved short-term survival. PMID- 1642192 TI - Factors influencing the development of hypercholesterolemia after cardiac transplantation. AB - Although hypercholesterolemia is a frequent complication in cardiac transplant recipients, the exact mechanisms contributing to its development are not known. Cholesterol levels in 151 thoracic transplant patients treated with cyclosporine, azathioprine and prednisone were retrospectively examined to evaluate the factors influencing the heterogeneity of changes after the first year after transplantation in patients on a standard 3-drug immunosuppression regimen. Three groups were compared including ischemic heart transplant (n = 72), nonischemic heart transplant (n = 64) and heart-lung/lung transplant (n = 15) recipients. After the first year, 64 patients (43%) developed consistent hypercholesterolemia (greater than 240 mg/dl) for which pharmacologic treatment was initiated. Forty eight patients (67%) in the ischemic heart transplant group required treatment, significantly (p less than 0.001) greater than both the nonischemic (n = 14; 22%) and heart-lung/lung transplant (n = 2; 13%) group. Univariate and forward stepwise multivariate regression analysis identified 4 factors that were all significantly and independently correlated with follow-up cholesterol including prednisone dose (p less than 0.001), baseline cholesterol (p less than 0.001), glucose (p less than 0.001) and weight gain (p less than 0.01). Changes in triglycerides in the 3 groups of patients were similar to changes in cholesterol. Furthermore, the increase in cholesterol in patients requiring treatment was primarily due to an increase in low-density lipoprotein cholesterol. These data demonstrate that hypercholesterolemia is common in heart transplant recipients treated with standard 3-drug immunosuppression and generally develops within the first 2 years after transplantation. However, this complication is not uniform and appears to be most strongly related to previous coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642193 TI - Error rates with which endomyocardial biopsy specimens are graded for rejection after cardiac transplantation. AB - Control of the immune response to the transplanted organ is fundamental to the success of transplantation. Endomyocardial biopsy to diagnose and grade rejection is the mainstay in achieving this control. As rejection tends to be a patchy process, accurate diagnosis depends on adequate sampling from the myocardium. This study estimates the error rates with which biopsy specimens are graded. The results of 459 biopsy sets, in which at least 4 fragments were graded, were analyzed. Combinations of grades observed at the same biopsy session were used to estimate error rates. An E-M algorithm was used to estimate error rates. Predictive probabilities of true grades, given a set of 4 graded fragments, were calculated using Bayes theorem. If 4 fragments at a biopsy session were negative there was a 0.02% chance of missing clinically significant rejection (moderate or severe). Similarly, if minimal rejection was the highest grade observed, the probability of missing moderate-severe rejection was negligible, between 0.06 and 0.09%. However, where mild rejection is the highest observed on the 4 fragments, there is between a 2% (1 mild fragment) and 28% (4 mild fragments) chance of moderate-severe rejection being the underlying grade. This study concludes that 4 fragments are adequate as a minimum in most cases. However, if only 4 fragments are available, and greater than or equal to 3 are graded mild, the risk of missing moderate-severe rejection is unacceptably high, and repeat biopsy or treatment may be indicated. PMID- 1642194 TI - Peak exercise left ventricular performance in normal subjects and in athletes assessed by first-pass radionuclide angiography. AB - The role of Frank-Starling law of the heart in determining the increase in cardiac output during exercise in humans is still controversial (e.g., the mechanisms responsible for the enhancement of left ventricular [LV] filling during the shortened diastolic interval). Ten weight lifters, 12 swimmers and 12 sedentary subjects who underwent maximal upright bicycle exercise testing were studied. First-pass radionuclide angiography was performed both at rest and at peak exercise using a multicrystal gamma camera. Compared with resting values, heart rate and cardiac index at peak exercise increased by 101 +/- 16 beats/min (p less than 0.001) and 6.7 +/- 2.8 liters/min/m2 (p less than 0.001) in weight lifters, by 96 +/- 9 beats/min (p less than 0.001) and 9.5 +/- 2 liters/min/m2 (p less than 0.001) in swimmers, and by 103 +/- 9 beats/min (p less than 0.001) and 7.3 +/- 1.8 liters/min/m2 (p less than 0.001) in sedentary subjects. Stroke volume increased by 20.5 +/- 9.8 ml/m2 (p less than 0.001) in swimmers only. End diastolic volume at peak exercise did not change in weight lifters and in swimmers; it decreased by 8.2 +/- 8.6 ml/m2 (p less than 0.01) in sedentary subjects. A significant correlation was found between the decrease in end systolic volume and the increase in peak rapid filling rate at peak exercise in all 3 groups (r = 0.65, p less than 0.05 in weight lifters; r = 0.59, p less than 0.05 in swimmers; r = 0.67, p less than 0.05 in sedentary subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642195 TI - Doppler echocardiographic assessment of aortic stenosis using the peak velocity ratio. PMID- 1642196 TI - Comparison of thermodilution and Fick methods for measurement of cardiac output in tricuspid regurgitation. PMID- 1642197 TI - Reported frequency of coronary arterial narrowing by angiogram in patients with valvular aortic stenosis. PMID- 1642198 TI - Specificity of electrocardiographic stress test in women versus men. PMID- 1642199 TI - Assessment of rate smoothing in dual-chamber pacemakers. PMID- 1642200 TI - Intraoperative percutaneous double-balloon valvuloplasty versus surgical commissurotomy for mitral valve stenosis. PMID- 1642201 TI - Is tropical pancreatitis premalignant? AB - Pancreatic adenocarcinoma occurred in 22 of 266 patients with tropical pancreatitis presenting over an 8-yr period (8.3%). We compared the data on three groups: group 1, patients with tropical pancreatitis (benign, n = 82); group 2, tropical pancreatitis with super-imposed malignancy (n = 22), and group 3, those with de novo cancer (n = 76). Factors associated with high risk for cancer in tropical pancreatitis were age greater than 40 yr, short symptom duration, weight loss, mass on ultrasound, and ductal block on endoscopic retrograde cholangiopancreatography. Tropical pancreatic cancers had distinct differences from de novo cancers: younger mean age (47 vs. 61 yr), calculi in all (vs. none in group 3), diabetes in 16 of 22 (73%) versus 18 of 76 (24%), and tumors in body and tail in 16 of 22 (73%) versus 26 of 76 patients (34%). In group 2, survival was poorer (10 vs. 17 months, p less than 0.01) than in group 3 (those with de novo cancer). Two of five resected specimens in group 2 showed features of dysplasia, in addition to cancer. Tropical pancreatitis has a high association with cancer. Malignancy occurring in tropical pancreatitis is distinct from de novo cancer. When considered in the light of the low incidence of pancreatic cancer in southern India, the above evidence suggests a possible etiological relationship. PMID- 1642202 TI - A comparative study of once-a-day morning and once-a-day bedtime administration of 40 mg famotidine in treating gastric ulcers. AB - A randomized controlled study comparing once-a-day morning and once-a-day bedtime administration of 40 mg famotidine in treating gastric ulcers was carried out in 179 Japanese patients. Endoscopic examinations were performed at the baseline and repeated at 4-wk intervals until healing was confirmed. One hundred and sixty four patients fulfilled the evaluation criteria (81 in the morning group and 83 in the bedtime group). The healing rates were 50.7% after 4 wk and 88.9% after 8 wk in the morning group and 46.5% after 4 wk and 74.7% after 8 wk in the bedtime group. The difference was statistically significant after 8 wk. Significant reductions from baseline for overall pain, beginning during the first 3 days, were likewise found in the two treatment groups. However, the pain severity in hunger state 1 wk after treatment was significantly higher in the bedtime group than in the morning group. Thus, once-a-day morning administration of 40 mg famotidine seems to be superior to once-a-day bedtime administration of 40 mg famotidine in treating gastric ulcers. PMID- 1642203 TI - Historical case report of Sir William Johnson, the Mohawk Baronet. PMID- 1642204 TI - Cullen's sign: it doesn't always mean hemorrhagic pancreatitis. AB - Periumbilical ecchymosis, Cullen's sign, is most often considered a sign of hemorrhagic pancreatitis. We present a case of splenic rupture secondary to infectious mononucleosis in a middle-aged patient whose presenting complaint was the presence of Cullen's sign, secondary to the hemoperitoneum. The splenic rupture was managed conservatively, and the Cullen's sign resolved within 14 days of presentation. PMID- 1642205 TI - Crohn's disease of the duodenum complicated by pancreatitis and common bile duct obstruction. AB - It is well known that Crohn's disease can involve the duodenum, but isolated secondary complications such as pancreatitis or common bile duct obstruction have only rarely been reported, and never in the same patient. Herein, we describe a patient with duodenal Crohn's disease and both pancreatitis and calculous common bile obstruction. This unusual constellation of findings was managed with percutaneous techniques in which transhepatic catheterization of the bile duct permitted balloon dilatation of the ampulla of Vater, as well as a duodenal stricture. These maneuvers resulted in passage of the biliary stone and relief of the patient's symptoms. The management of this patient may serve as a guide possibly to delay or even prevent surgical intervention in similar cases of benign enteric strictures. PMID- 1642206 TI - Acute onset of celiac disease in the puerperium. AB - An acute, severe onset of celiac disease is very unusual in adults. We describe its occurrence postpartum in two patients. These, together with two similar cases previously reported, suggest a causal association with the puerperium. Possible causes include potentiation of a pathogenetic immune reaction and hormonal mechanisms. PMID- 1642207 TI - Endoscopic detection and therapy of colonic actinomycosis. AB - Abdominal actinomycosis is a disease that is difficult to diagnose nonoperatively. Usual manifestations are abscesses and draining sinus tracts. Treatment is typically surgical and requires prolonged intravenous antibiotics. Presented is a patient who underwent surveillance colonoscopy after resection for colon carcinoma. Diagnosis of colonic actinomycosis and subsequent resolution was demonstrated endoscopically after lengthy oral penicillin therapy (2 g/day for 1 yr). This case documents that resection may not be necessary to effect cure of abdominal actinomycosis. PMID- 1642208 TI - Diffuse-type gastric cancer in a young adult presenting with neurological symptoms and liver rupture. AB - A 27-yr-old man presented with neurological symptoms and subsequent painful liver enlargement. Cranial computerized tomographic scans and gastroscopy were negative. Ultrasound examination revealed nonhomogeneous echo pattern of the enlarged liver; a guided biopsy specimen suggested hepatoma. The patient died of hemorrhagic shock 5 days after liver biopsy and 4 wk after the initial presentation. Autopsy revealed diffuse-type gastric carcinoma as the primary lesion, liver ruptures at sites distant from the biopsy, thrombosis of the sagittal sinus, and widespread permeation of blood and lymphatic vessels with anaplastic carcinoma cells. The incidence of gastric cancer in young adults from the Cancer Registry of Slovenia is presented for the period from 1979 to 1987. Our case corroborates the importance of considering this malignancy early in the evaluation of young symptomatic patients. PMID- 1642209 TI - Carcinoma of the uncinate process of the pancreas with a peculiar clinical manifestation. AB - A total of 119 Japanese patients with pancreas head carcinoma were treated in the Department of Surgery I, Kyushu University Faculty of Medicine, Fukuoka, Japan, from January 1976 to December 1991. Three of the 119 patients had carcinoma in the uncinate process, with a 2.5% incidence of pancreas head carcinoma. Those three cases consisted of two men, one 55 and one 72 yr old, and one 62-yr-old woman. Two patients developed abdominal pain, whereas another was vomiting; no patients were icteric. Hypotonic duodenography showed an irregular mucosa of the inner area of the third portion of the duodenum in two and an obstruction of the duodenum in one. Drip infusion cholangiography and/or endoscopic retrograde cholangiopancreatography revealed no abnormality of the biliary tract or pancreatic ducts in any of the three. Ultrasonography showed a hypoechoic mass in the uncinate process in three, and computed tomography showed a low-density mass in the uncinate process in two with a displacement of the superior mesenteric vessels toward the anterior. Angiography showed encasement of the pancreatoduodenal arcade in three, the dorsal pancreatic artery in two, and the middle colic artery in two. No neovascularity or tumor staining was present. Two patients underwent a pancreatoduodenectomy, and the other had a bypass operation (gastrojejunostomy). The histopathologic diagnosis was well-differentiated adenocarcinoma, mucinous carcinoma, and adenosquamous carcinoma, respectively. Two patients died from local recurrence and/or distant metastasis 5 and 6 months after a radical resection, and the other died 3 months after clinical diagnosis. Peculiar clinicopathologic features of these patients with pancreas carcinoma arising in the uncinate process are reported herein, and the clinical problems of this disorder are briefly discussed. PMID- 1642210 TI - Copper deficiency and microcytic anemia resulting from prolonged ingestion of over-the-counter zinc. AB - Isolated copper deficiency occurred in a 57-yr-old man who had ingested massive quantities of zinc for more than 18 months. The patient presented with microcytic anemia and had normal gastrointestinal function with no evidence of occult blood loss. Dietary zinc in large doses leads to copper deficiency by antagonizing copper absorption. With discontinuance of zinc, the anemia and hypocupremia promptly corrected. The relationship between zinc, copper deficiency, and iron metabolism is reviewed. PMID- 1642211 TI - Biofeedback in anismus: the truth be known? PMID- 1642212 TI - Autoimmune hepatitis, hepatitis C, and interferon: look before you leap. PMID- 1642213 TI - Experimental pancreatolithiasis: association with chronic alcoholic pancreatitis. PMID- 1642214 TI - Chronic non-B, non-C hepatitis: report from Pakistan. PMID- 1642215 TI - Hepatic dysfunction induced by streptokinase. PMID- 1642216 TI - Visual endoscopic indicator of Helicobacter pylori infection. PMID- 1642217 TI - Portal hypertensive intestinal vasculopathy: a review of the clinical, endoscopic, and histopathologic features. AB - Over the past decade, awareness of the association between portal hypertension and changes in the intestinal circulation has increased. Most of the observations have been made by endoscopic examination and biopsy of the mucosa. The fundamental pathologic change is a vasculopathy. Portal hypertensive intestinal vasculopathy (PHIV) most often involves the stomach (gastropathy) and can be a common source of bleeding. The significance of small bowel involvement (enteropathy) is unknown. Colon involvement (colopathy) has been associated with bleeding, and mimics inflammatory bowel disease. The reliability of endoscopic appearances and histologic examination in establishing the diagnosis is questionable. Recent observations of other diagnostic modalities and associated physiologic alterations and treatment options are discussed. Further prospective evaluations that use uniform terminology for endoscopic and histologic descriptions are needed to establish criteria for accurate diagnosis and assessment of response to treatment. PMID- 1642218 TI - Role of endoscopic retrograde cholangiopancreatography after orthotopic liver transplantation. AB - We reviewed the records of 20 liver transplant patients who underwent 28 procedures [endoscopic retrograde cholangiopancreatography (ERCP)] to rule out biliary obstruction, treat bile leaks, dilate and/or stent strictures, or remove stones and debris. Three patients (two with abnormal T-tube cholangiograms and one with hyperbilirubinemia) underwent ERCP to rule out obstruction. Therapeutic ERCP (sphincterotomy with balloon dilatation or stone extraction) was successful in 16 of 17 patients, including seven of nine in whom there was resolution of bile leaks without the use of stents or surgery. Mild pancreatitis occurring in one patient was the only complication experienced that was related to ERCP. We conclude that ERCP is a safe and important modality in the medical management of biliary tract complications after orthotopic liver transplantation. PMID- 1642219 TI - The LES locator: accurate placement of an electrode for 24-hour pH measurement with a combined solid state pressure transducer. AB - Twenty-four-hour esophageal pH monitoring is the gold standard for diagnosing gastroesophageal reflux disease. A possible limitation to the widespread use of this test is that manometry is required for accurate placement of the pH electrode 5 cm above the lower esophageal sphincter. We compared the accuracy of a single solid state pressure transducer, combined with a pH electrode, in determining the proximal border of the lower esophageal sphincter (LES) with the values obtained from stationary manometry in 40 patients referred to our laboratory for 24-h pH studies. Not only was there a strong correlation (r = 0.9) between LES values obtained by the two techniques, but none of the values obtained by the single solid state transducer were outside the clinically accepted range of greater than +/- 3 cm. The presence of a hiatal hernia or low sphincter pressure did not affect these measurements. The larger probe was tolerated somewhat less well (p = 0.02) than a standard antimony electrode during the prolonged pH studies. In conclusion, a single solid state pressure transducer on a pH probe with the help of a LES locator accurately identifies the proximal border of the LES. Therefore, stationary esophageal manometry is no longer needed prior to 24-h pH monitoring, potentially making this important clinical tool available to a wider variety of clinicians at all levels of the health care system, in investigating gastroesophageal reflux and its protean clinical presentations. PMID- 1642220 TI - An index of disease activity in patients with ulcerative colitis. AB - Quantification of disease severity was studied in 72 patients with ulcerative colitis, who had undergone total 85 clinical courses. We performed a multiple stepwise regression analysis, according to Truelove and Witts' classification, with disease severity as a dependent variable, and with 18 clinical, laboratory, and endoscopic parameters as independent variables. Results showed that disease severity in patients with ulcerative colitis is significantly influenced by five factors, namely, bloody stool, bowel movements, erythrocyte sedimentation rate (ESR), hemoglobin (Hb), and serum albumin. The activity index (AI) developed for ulcerative colitis is expressed as follows: AI = 60 x blood stool + 13 x bowel movements + 0.5 x ESR - 4 x HB - 15 x albumin + 200. Index values below 150, values between 150 and 220, and values above 220 nearly corresponded to mild, moderate, and severe disease, respectively, in Truelove and Witts' classification. We believe that the activity index is useful in evaluation of the effect of medical treatment in patients with ulcerative colitis. Its most important value will be in therapeutic trials. PMID- 1642221 TI - Psychological evaluation of patients with severe idiopathic constipation: which instrument to use. AB - We prospectively evaluated 38 patients with chronic severe idiopathic constipation who failed to respond to conventional therapy. Colonic transit studies, the Hopkins Symptom Checklist (SCL-90-R), and the Minnesota Multiphasic Personality Inventory (MMPI) were completed. Colonic transit studies identified 23 patients with slow transit and 15 with normal transit. Patients with normal transit constipation scored higher than those with slow transit on every scale of both the SCL-90-R and MMPI, but the SCL-90-R appeared to detect greater differences between the two groups. We conclude that the SCL-90-R is the preferred psychological instrument to evaluate patients with chronic severe constipation who fail to respond to conventional therapy. It provides information similar to the MMPI with which to measure behavioral profiles of patients in an office setting, and it can be completed and scored more rapidly. PMID- 1642223 TI - Endoscopic stent placement for obstructive jaundice secondary to metastatic malignancy. AB - In patients with malignancy, jaundice may result from hepatic infiltration or metastatic lymph nodal compression along the bile duct. We attempted endoscopic stent placement on 31 consecutive patients with biliary obstruction from malignant adenopathy, with and without computerized tomographic (CT) scan evidence of hepatic parenchymal metastases. Endoscopic or combined endoscopic percutaneous decompression was accomplished in 28 patients. Fifteen patients (53.6%) had CT evidence of concomitant metastatic disease to the liver. Thirteen patients had obstructing adenopathy only. Mean survival for patients with hepatic metastases after relief of extrahepatic obstruction was 117.4 days (range 9-386 days). Mean survival after biliary decompression in patients without hepatic involvement was significantly longer at 364.3 days (range 52-1098 days; p = 0.0087). Bilirubin levels fell in all patients in this group. No patient died from complications of obstruction or stent placement. Our data support the conclusion that patients with extrahepatic metastatic biliary obstruction without hepatic metastases have improved survival, compared with patients with both obstruction and hepatic involvement. In the absence of hepatic parenchymal involvement, endoscopic stent placement can safely and effectively palliate metastatic extrahepatic obstruction. Controlled trials are needed to assess the effect of such stenting on survival. PMID- 1642222 TI - Enteric-coated charcoal as a means of blinding studies comparing bismuth and H2 receptor antagonists. AB - Clinical trials comparing H2-receptor antagonists and bismuth-containing regimens in ulcer healing, ulcer relapse, or dyspepsia have not been double-blind, because bismuth darkens stools. This study was designed to determine whether enteric coated charcoal could darken stools of subjects taking an H2-receptor antagonist without interfering with absorption of the drug. Twelve healthy volunteers participated in a randomized, double-blind, crossover trial of oral ranitidine (300 mg at bedtime) alone, ranitidine plus bismuth (30 ml Pepto-Bismol four times daily), and ranitidine plus enteric-coated charcoal (four tablets daily). Mean stool colors both with ranitidine plus charcoal and with ranitidine plus bismuth were significantly darker than with ranitidine alone, but were not significantly different from each other. Blood levels of ranitidine during the 10 h after its administration did not differ significantly among the three regimens. We conclude that enteric-coated charcoal can be used to blind clinical trials comparing an H2 receptor antagonist (e.g., ranitidine) and a bismuth regimen. PMID- 1642224 TI - A prospective randomized study of the injurious effects of aspirin and naproxen on the gastroduodenal mucosa in patients with rheumatoid arthritis. AB - A prospective double-blind randomized placebo-controlled study was conducted to compare the injurious effects of aspirin and naproxen on the gastroduodenal mucosa. Patients with rheumatoid arthritis attending the immunology clinic of a tertiary care center were included in the study. Ninety consecutive patients were randomized to receive aspirin, naproxen, or placebo. Clinical evaluation was done every 2 wk. Upper gastrointestinal endoscopy, biopsies from the gastric antrum and duodenum for histological examination, and Helicobacter pylori studies were done at entry and after 2 months. The number of patients with dyspeptic symptoms was similar in the aspirin (12) and naproxen (9) groups. In both cases, however, it was higher (p less than 0.01) than in the placebo group (none). Naproxen was associated with a higher score of endoscopic abnormalities in the gastric body (0.6 +/- 1.3) than aspirin (0.2 +/- 0.6) or placebo (0.03 +/- 0.18). H. pylori was present in a similar proportion of patients in the three groups (33-43%). A greater fall in hemoglobin was observed with aspirin (0.35 +/- 0.48 g%) and naproxen (0.44 +/- 0.53 g%) than with placebo (0.09 +/- 0.4 g%). The present study suggests that aspirin and naproxen produce a similar degree of injury to the gastroduodenal mucosa. PMID- 1642225 TI - Organized medical genetics at a crossroad. PMID- 1642226 TI - Human dermatosparaxis: a form of Ehlers-Danlos syndrome that results from failure to remove the amino-terminal propeptide of type I procollagen. AB - Dermatosparaxis is a recessively inherited connective-tissue disorder that results from lack of the activity of type I procollagen N-proteinase, the enzyme that removes the amino-terminal propeptides from type I procollagen. Initially identified in cattle more than 20 years ago, the disorder was subsequently characterized in sheep, cats, and dogs. Affected animals have fragile skin, lax joints, and often die prematurely because of sepsis following avulsion of portions of skin. We recently identified two children with soft, lax, and fragile skin, which, when examined by transmission electron microscopy, contained the twisted, ribbon-like collagen fibrils characteristic of dermatosparaxis. Skin extracts from one child contained collagen precursors with amino-terminal extensions. Cultured fibroblasts from both children failed to cleave the amino terminal propeptides from the pro alpha 1(I) and pro alpha 2(I) chains in type I procollagen molecules. Extracts of normal cells cleaved to collagen, the type I procollagen synthesized by cells from both children, demonstrating that the enzyme, not the substrate, was defective. These findings distinguish dermatosparaxis from Ehlers-Danlos syndrome type VII, which results from substrate mutations that prevent proteolytic processing of type I procollagen molecules. PMID- 1642227 TI - Isolation, characterization, and regional mapping of microclones from a human chromosome 21 microdissection library. AB - Thirty-four unique-sequence microclones were isolated from a previously described microdissection library of human chromosome 21 and were regionally mapped using a cell hybrid mapping panel which consists of six cell hybrids and divides chromosome 21 into eight regions. The mapping results showed that the microclones were unevenly distributed along chromosome 21, with the majority of microclones located in the distal half portion of the long arm, between 21q21.3 and 21qter. The number of unique-sequence clones began to decrease significantly from 21q21.2 to centromere and extending to the short arm. This finding is consistent with those reported in other chromosome 21 libraries. Thus, it may be inferred that the proximal portion of the long arm of chromosome 21 contains higher proportions of repetitive sequences, rather than unique sequences or genes. The microclones were also characterized for insert size and were used to identify the corresponding genomic fragments generated by HindIII. In addition, we demonstrated that the microclones with short inserts can be efficiently used to identify YAC (yeast artificial chromosome) clones with large inserts, for increased genomic coverage for high-resolution physical mapping. We also used 200 unique-sequence microclones to screen a human liver cDNA library and identified two cDNA clones which were regionally assigned to the 21q21.3-q22.1 region. Thus, generation of unique-sequence microclones from chromosome 21 appears to be useful to isolate and regionally map many cDNA clones, among which will be candidate genes for important diseases on chromosome 21, including Down syndrome, Alzheimer disease, amyotrophic lateral sclerosis, and one form of epilepsy. PMID- 1642228 TI - Assessment of amyloid beta-protein precursor gene mutations in a large set of familial and sporadic Alzheimer disease cases. AB - A genetic locus associated with familial Alzheimer disease (FAD) and a candidate gene, APP, encoding the amyloid protein precursor have both been assigned previously to chromosome 21, and, in a few FAD families, mutations of APP have been detected. However, obligate crossovers between APP and FAD have also been reported in several FAD pedigrees, including FAD4, a large kindred showing highly suggestive evidence for linkage of the disorder to chromosome 21. In case the apparent APP crossover in FAD4 actually represented an intragenic recombination event or segregation of different mutations in different family branches, we have performed a more detailed assessment of APP as a candidate gene in this family. The entire coding region of the APP gene was sequenced for FAD4 and for FAD1, a second large kindred. No mutations were found, indicating that, in at least one chromosome 21-linked FAD pedigree, the gene defect is not accounted for by a mutation in the known coding region of the APP gene. A total of 25 well characterized early- and late-onset FAD pedigrees were typed for genetic linkage to APP, to assess the percentage of FAD families predicted to carry mutations in the APP gene. None of the FAD families yielded positive lod scores at a recombination fraction of 0.0. To estimate the overall prevalence of FAD associated mutations in the beta A4 domain of APP, we sequenced exons 16 and 17 in 30 (20 early- and 10 late-onset) FAD kindreds and in 11 sporadic AD cases, and we screened 56 FAD kindreds and 81 cases of sporadic AD for the presence of the originally reported FAD-associated mutation, APP717 Val----Ile (by BclI digestion). No APP gene mutations were found in any of the FAD families or sporadic-AD samples examined in this study, suggesting that the mutations in exons 16 and 17 are a rare cause of FAD. Overall, these data suggest that APP gene mutations account for a very small portion of FAD. PMID- 1642229 TI - Strategies for characterizing highly polymorphic markers in human gene mapping. AB - Before new markers are thoroughly characterized, they are usually screened for high polymorphism on the basis of a small panel of individuals. Four commonly used screening strategies are compared in terms of their power to correctly classify a marker as having heterozygosity of 70% or higher. A small number of typed individuals (10, say) are shown to provide good discrimination power between low- and high-heterozygosity markers when the markers have a small number of alleles. Characterizing markers in more detail requires larger sample sizes (e.g., at least 80-100 individuals) if there is to be a high probability of detecting most or all alleles. For linkage analyses involving highly polymorphic markers, the practice of arbitrarily assuming equal gene frequencies can cause serious trouble. In the presence of untyped individuals, when gene frequencies are unequal but are assumed to be equal in the analysis, recombination-fraction estimates tend to be badly biased, leading to strong false-positive evidence for linkage. PMID- 1642230 TI - Different patterns of X inactivation in MZ twins discordant for red-green color vision deficiency. AB - Two female identical twins who were clinically normal were obligatory heterozygotes for X-linked deuteranomaly associated with a green-red fusion gene derived from their deuteranomalous father. On anomaloscopy, one of the twins was phenotypically deuteranomalous while the other had normal color vision. The color vision-defective twin had two sons with normal color vision and one deuteranomalous son. X-inactivation analysis was done with the highly informative probe M27 beta. This probe detects a locus (DXS255) which contains a VNTR and which is somewhat differentially methylated on the active and inactive X chromosomes. In skin cells of the color vision-defective twin, almost all paternal X chromosomes with the abnormal color-vision genes were active, thereby explaining her color-vision defect. In contrast, a different pattern was observed in skin cells from the woman with normal color vision; her maternal X chromosome was mostly active. However, in blood lymphocytes, both twins showed identical patterns with mixtures of inactivated maternal and paternal X chromosomes. Deuteranomaly in one of the twins is explained by extremely skewed X inactivation, as shown in skin cells. Failure to find this skewed pattern in blood cells is explained by the sharing of fetal circulation and exchange of hematopoietic precursor cells between twins. These data give evidence for X inactivation of the color-vision locus and add another MZ twin pair with markedly different X-inactivation patterns for X-linked traits. PMID- 1642231 TI - A microdeletion of less than 250 kb, including the proximal part of the FMR-I gene and the fragile-X site, in a male with the clinical phenotype of fragile-X syndrome. AB - A gene designated "FMR-1" has been isolated at the fragile-X locus. One exon of this gene is carried on a 5.1-kb EcoRI fragment that exhibits length variation in fragile-X patients because of amplification of or insertion into a CGG-repeat sequence. This repeat probably represents the fragile site. The EcoRI fragment also includes an HTF island that is hypermethylated in fragile-X patients showing absence of FMR-1 mRNA. In this paper, we present further evidence that the FMR-1 gene is involved in the clinical manifestation of the fragile-X syndrome and also in the expression of the cellular phenotype. A deletion including the HTF island and exons of the FMR-1 gene was detected in a fragile X-negative mentally retarded male who presented the clinical phenotype of the fragile-X syndrome. The deletion involves less than 250 kb of genomic DNA, including DXS548 and at least five exons of the FMR-1 gene. These data support the hypothesis that loss of function of the FMR-1 gene leads to the clinical phenotype of the fragile-X syndrome. In the fragile-X syndrome, there are pathogenetic mechanisms other than amplification of the CGG repeat that do have the same phenotypic consequences. PMID- 1642232 TI - Further localization of X-linked hydrocephalus in the chromosomal region Xq28. AB - X-linked hydrocephalus (HSAS) is the most frequent genetic form of hydrocephalus. Clinical symptoms of HSAS include hydrocephalus, mental retardation, clasped thumbs, and spastic paraparesis. Recently we have assigned the HSAS gene to Xq28 by linkage analysis. In the present study we used a panel of 18 Xq27-q28 marker loci to further localize the HSAS gene in 13 HSAS families of different ethnic origins. Among the Xq27-q28 marker loci used, DXS52, DXS15, and F8C gave the highest combined lod scores, of 14.64, 6.53 and 6.33, respectively, at recombination fractions of .04, 0, and .05, respectively. Multipoint linkage analysis localizes the HSAS gene in the telomeric part of the Xq28 region, with a maximal lod score of 20.91 at 0.5 cM distal to DXS52. Several recombinations between the HSAS gene and the Xq28 markers DXS455, DXS304, DXS305, and DXS52 confirm that the HSAS locus is distal to DXS52. One crossover between HSAS and F8C suggests that HSAS gene to be proximal to F8C. Therefore, data from multipoint linkage analysis and the localization of key crossovers indicate that the HSAS gene is most likely located between DXS52 and F8C. This high-resolution genetic mapping places the HSAS locus within a region of less than 2 Mb in length, which is now amenable to positional cloning. PMID- 1642233 TI - Characterization of a deletion at Xq27-q28 associated with unbalanced inactivation of the nonmutant X chromosome. AB - We report the results of studies on the characterization of the mutation associated with marked unbalanced expression of the mutant X chromosome in a karyotypically normal girl with Hunter disease (mucopolysaccharidosis type II). Southern analysis of DNA extracted from somatic cell hybrids containing only the mutant X chromosome showed deletion of the Xq27.3-q28 loci: DXS297 (VK23AC), DXS293 (VK16), FRAXA (pfxa3), DXS296 (VK21A), and the 3' end of the iduronatesulfatase (IDS) gene. The flanking loci--DXS52 (St14-1), DXS304 (U6.2), and DXS369 (RN1)--were intact. On the basis of these results, we concluded that the mutation was a simple deletion extending a maximum of 3-5 cM to the centromeric side of the IDS gene. Both Southern analysis of DNA from somatic cell hybrids, using short segments of IDS cDNA, and PCR of reverse-transcribed RNA from cultured skin fibroblasts indicated that the telomeric terminus of the deletion was localized to a region near the middle of the coding sequences of the gene. PMID- 1642234 TI - Mode of inheritance of nonsyndromic cleft lip with or without cleft palate: a reanalysis. AB - Nonsyndromic cleft lip with or without cleft palate (CL +/- P) is traditionally recognized as a multifactorial threshold trait (MFT). Recently, however, evidence for the involvement of a major gene in the etiology of CL +/- P has been reported. To assess the potential for major-gene involvement in the etiology of this trait, familial recurrence patterns from several family studies of CL +/- P were reanalyzed. The recurrence patterns in first-degree relatives of CL +/- P probands were found to be compatible with the expectations for either an MFT or a generalized single-major-locus (gSML) trait. The use of multiple thresholds based on proband sex, defect bilaterality, or palatal involvement did not help to discriminate between these models. However, the pattern of recurrence among MZ twins and more remote relatives of CL +/- P probands is not consistent with gSML inheritance but is compatible with either an MFT model or a model specifying multiple interacting loci. For such a model, no single locus can account for more than a sixfold increase in risk to first-degree relatives. These findings have important implications with regard to the feasibility of detecting linkage to loci conferring susceptibility to CL +/- P. PMID- 1642235 TI - Segregation analysis of cancer in families of childhood soft-tissue-sarcoma patients. AB - This paper presents the analysis of familial cancer data collected in a hospital based study of 159 childhood soft-tissue-sarcoma patients. Two different statistical models detected excess aggregation of cancer, which could be explained by a rare dominant gene. For each kindred, we estimated the probability of the observed cancer distribution under the dominant-gene model and identified 12 families that are the most likely to be segregating the gene. Two of those families have confirmed germ-line mutations in the p53 tumor-suppressor gene. The relative risk of affection for children who are gene carriers was estimated to be 100 times the background rate. Females were found to have a slightly higher age specific penetrance, but maternal and paternal lineages made equal contributions to the evidence in favor of the dominant gene. The proband's histology, ethnicity, and age at diagnosis were evaluated to determine whether any of these altered the probability of affection in family members. Only embryonal rhabdomyosarcoma was found to be a significant covariate under the dominant-gene model. While molecular genetic studies of familial cancer will eventually provide answers to the questions of genetic heterogeneity, age- and site-specific penetrance, mutation rates, and gene frequency, information from statistical models is useful for setting priorities and defining hypotheses. PMID- 1642236 TI - Functional profile of the human fetal gamma-globin gene upstream promoter region. AB - We performed a systematic functional analysis of the human gamma-globin promoter to identify its activator domains. We used a panel of truncation and scanning mutants as well as transfection in human K562 fetal erythroid cells. The various mutations produced relatively small changes in promoter function in both transient and stable transfection assays. The CACCC region and the region containing the binding sites for protein GATA-1 behaved as activator domains. We also obtained evidence for a minor activator site in the - 200 to - 190 region. The results are consistent with the interpretation that gamma-globin gene regulation may occur in part through multiple small effects of promoter elements. PMID- 1642237 TI - Regional mapping of facioscapulohumeral muscular dystrophy gene on 4q35: combined analysis of an international consortium. AB - Members of an international consortium for linkage analysis of the facioscapulohumeral muscular dystrophy (FSHD) gene have pooled data for joint analyses, in an attempt to determine the precise location of the FSHD gene and the order of four DNA markers on 4q35 region. Six laboratories determined a total of 3,078 genotypes in 65 families, consisting of a total of 504 affected subjects and 559 unaffected subjects. For each marker, a mean of 648 meioses were informative. D4S139 and D4S163 were identified as the closest linked markers to the FSHD locus, with 99% upper confidence intervals of recombination fractions of .08 and .10, respectively. We have used the CRI-MAP program to construct the most likely order of cen-D4S171-F11-D4S163-D4S139-FSHD-tel, with favorable odds of 10(8)-10(114) over all other orders except that in which F11 and D4S171 are reversed, for which the odds ratio was 191:1. With this order, the genetic map of this region extends 25.5 cM in males and 13.8 cM in females (averaging 19.5 cM for sexes combined); the sex difference was statistically significant (P = .0013). Comparison between families for the two-point and multipoint lod scores involving FSHD showed no evidence for heterogeneity of this disorder. However, after the completion of this analysis, one large family which might show heterogeneity was identified. In view of this and the fact that all of the linked markers reside on the same side of the FSHD locus, the clinical application of these markers is not recommended at this time. PMID- 1642238 TI - The mapping of chromosome 4q markers in relation to facioscapulohumeral muscular dystrophy (FSHD). AB - Four DNA markers on the distal long arm of chromosome 4 have been analyzed for their linkage relationship to facioscapulohumeral muscular dystrophy (FSHD) in a series of 23 families with this disease. Two hypervariable markers, pH30 (D4S139) and EFD 139.1 (D4S184), both show close linkage with the disorder, with a maximum recombination fraction (theta max) of .02 and a maximum lod score (Zmax) of 36.77 and 34.50, respectively; two other markers, the locus for factor XI (F11) and the microsatellite marker Mfd22 (D4S171), both show less close linkage, with respective theta max of .16 (Zmax = 3.40) for F11 and .24 (Zmax = 1.61) for D4S171. While the relative ordering and orientation of the loci on the chromosome remain provisional, analysis of 15 individual recombination events in seven families supports the order D4S171-F11-D4S184-D4S139-FSHD, with the disease locus telomeric to all four markers. PMID- 1642239 TI - Genetic linkage map of facioscapulohumeral muscular dystrophy and five polymorphic loci on chromosome 4q35-qter. AB - A genetic map of five polymorphic markers in the area of the facioscapulohumeral muscular dystrophy (FSHD) gene on chromosome 4q35-qter has been constructed. With these five markers, a number of recombinants have been identified that allow ordering of the marker and the disease loci. The most likely locus order and the relative position of the FSHD gene supported by the recombinants is centromere D4S171-F11-D4S187-D4S163-D4S139-FS HD-telomere. However, at least one recombination event appears to be inconsistent with this order and suggests a location of FSHD proximal to D4S139. PMID- 1642240 TI - Linkage analyses of five chromosome 4 markers localizes the facioscapulohumeral muscular dystrophy (FSHD) gene to distal 4q35. AB - The genetic locus for facioscapulohumeral muscular dystrophy (FSHD) has been mapped to chromosome 4. We have examined linkage to five chromosome 4q DNA markers in 22 multigenerational FSHD families. Multipoint linkage analyses of the segregation of four markers in the FSHD families and in 40 multigenerational mapping families from the Centre d'Etude du Polymorphisme Humaine enabled these loci and FSHD to be placed in the following order: cen-D4S171-factor XI-D4S163 D4S139-FSHD-qter. One interval, D4S171-FSHD, showed significant sex-specific differences in recombination. Homogeneity tests supported linkage of FSHD to these 4q DNA markers in all of the families we studied. The position of FSHD is consistent with that generated by other groups as members of an international FSHD consortium. PMID- 1642241 TI - Linkage studies in facioscapulohumeral muscular dystrophy (FSHD). AB - Facioscapulohumeral muscular dystrophy (FSHD) has been localized to the 4q35-qter region of chromosome 4. Linkage analyses of two polymorphic markers from the region, D4S139 and D4S163, have been carried out using four large multigenerational FSHD families. The results indicate that both markers are closely linked to FSHD, with D4S139 being the closest proximal marker to FSHD. PMID- 1642242 TI - Linkage localization of facioscapulohumeral muscular dystrophy (FSHD) in 4q35. AB - Fasioscapulohumeral muscular dystrophy (FSHD) has recently been localized to 4q35. We have studied four families with FSHD. Linkage to the 4q35 probes D4S163, D4S139, and D4S171 was confirmed. We found no recombinants helpful in detailed localization of the FSHD gene. Two of our families include males with a rapidly progressive muscle disease that had been diagnosed, on the basis of clinical features, as Duchenne muscular dystrophy. One of these males is available for linkage study and shares the haplotype of his FSHD-affected aunt and cousin. PMID- 1642243 TI - Genetic and physical mapping on chromosome 4 narrows the localization of the gene for facioscapulohumeral muscular dystrophy (FSHD). AB - We have used a combination of classical RFLPs and PCR-based polymorphisms including CA repeats and single-strand conformation polymorphisms to generate a fine-structure genetic map of the distal long arm of chromosome 4q. This map is now genetically linked to the pre-existing anchor map of 4pter-4q31 and generates, for the first time, a complete linkage map of this chromosome. The map consists of 32 anchor loci placed with odds of greater than 1,000:1. The high resolution map in the cytogenetic region surrounding 4q35 provides the order 4cen D4S171-F11-D4S187-D4S163-D4S139-4q ter. When we used somatic cell hybrids from a t(X;4)(p21;q35) translocation, these five markers fell into three groups consistent with the genetic map-D4S171 and F11 in 4pter-4q35, D4S163 and D4S139 in 4q35-4qter, and D4S187 as a junction fragment between these two regions. These markers are in tight linkage to the gene for facioscapulo-humeral muscular dystrophy (FSHD) mapped to this region by several collaborating investigators and provide a framework for further detailed analysis of this region. PMID- 1642244 TI - Fast screening methods to detect mutations of spectrin in subjects with hereditary elliptocytosis. PMID- 1642245 TI - Van der Woude syndrome and nonsyndromic cleft lip and palate. PMID- 1642246 TI - Presentation of the Southern Society for Clinical Investigation Founder's Medal to Dr. Daniel W. Foster. PMID- 1642247 TI - Cicletanine blunts the pulmonary pressor response to acute hypoxia in rats. AB - Cicletanine (CIC) recently has been shown to lower systemic arterial pressure in hypertensive animals and man by a mechanism that may involve potentiation of the vasodilator effect of atrial natriuretic peptide (ANP). We previously have shown that ANP prevents acute hypoxia-induced pulmonary vasoconstriction and modulates the severity of chronic hypoxic pulmonary hypertension. The current study tested the hypothesis that CIC inhibits the pulmonary pressor response to acute hypoxia by a cyclic guanosine monophosphate (cGMP)-dependent mechanism. Catheters were placed in the pulmonary arteries of Sprague-Dawley rats through the right jugular vein using a closed chest technique, and in the aorta through the right femoral artery. After a 24 hour recovery, CIC (600 mg/kg) or vehicle was administered orally by gavage to conscious rats 4 hours prior to exposure to 10% oxygen at ambient pressure or to room air. Mean pulmonary arterial pressure (MPAP) and mean systemic arterial pressure (MSAP) and heart rate (HR) were monitored for 3 hours. CIC attenuated the acute pulmonary pressor response to hypoxia (MPAP = 24.5 +/- 1.0 mm Hg in the "hypoxic+CIC" group vs. 29.9 +/- 1.0 mm Hg in the "hypoxic+vehicle" group; p less than 0.05 at 3 hours of hypoxic exposure), but had no significant effect on MSAP or HR. CIC had no effect on MPAP, MSAP, or HR in air control rats. Acute hypoxia caused significant increases in plasma ANP and cGMP and in kidney cGMP content, but CIC administration did not alter these parameters further. This is the first demonstration that acute administration of CIC attenuates the pulmonary pressor response to acute hypoxia in conscious rats. PMID- 1642249 TI - Effect of occlusive dressings on the stratum corneum water holding capacity. AB - Occlusion of the skin is used in clinical dermatology to promote wound healing and to increase the transcutaneous penetration of topically applied drugs. These effects are related to the degree of occlusion exerted and depend on the physicochemical nature of the dressing. We have evaluated the effects of four different materials on the skin barrier and the stratum corneum water holding capacity (WHC) using the Plastic Occlusion Stress Test (POST). The following materials were compared: hydrocolloid dressing, polyurethane film, polyethylene film, and a plastic chamber. These devices were applied on the volar forearm for 24 hours in 10 healthy volunteers (mean age 32 +/- 4 years). Upon their removal, the stratum corneum WHC, measured as skin surface water loss (SSWL), was recorded continuously for 25 minutes using an Evaporimeter. SSWL decay curves showed significant differences between the occlusive materials (analysis of variance, p less than 0.01). Higher SSWL values were recorded in sites occluded with the plastic chamber, whereas the polyurethane film resulted in poor occlusive capacity. Hydrocolloid dressing and polyethylene gave similar responses with higher WHC values compared to polyurethane (p less than 0.05). The relevance of these findings to clinical dermatology in terms of wound healing and drug absorption is discussed. PMID- 1642248 TI - Vitamin A in hypercholesterolemia. AB - This study evaluated the relationship between plasma vitamin A and cholesterol in 48 patients with hypercholesterolemia studied before and after treatment with a cholesterol-lowering diet, with or without lipid-lowering medication. Plasma vitamin A levels were higher in hypercholesterolemic subjects than in healthy controls (2.58 +/- 0.15 vs. 1.82 +/- 0.14 mmol/L, p = 0.025) despite similar values for retinol binding protein (RBP). Successful cholesterol lowering, defined as greater than 25% reduction in low density lipoprotein cholesterol, was achieved in 16 patients. In this subset, plasma vitamin A declined from 3.00 +/- 0.32 (pretreatment) to 2.34 +/- 0.15 mmol/L (post treatment; p = 0.018). A nonsignificant increase in RBP was observed, resulting in a significant decrease in the molar ratio of vitamin A to RBP (1.05 +/- 0.06 vs. 0.80 +/- 0.05, p = 0.013). These data suggest an interaction between vitamin A and cholesterol that is independent of the transport mechanisms for vitamin A in association with chylomicrons (post absorptive) and with RBP. Further examinations of the form or forms of vitamin A (retinol, retinyl ester), its distribution within the plasma lipoproteins, and the mechanisms of origin and removal are warranted to explain these findings. PMID- 1642250 TI - Case report: severe pyoderma associated with familial Mediterranean fever- favorable response to colchicine in three patients. AB - Familial Mediterranean fever (FMF) is an autosomal recessive disorder that occurs most frequently among Sephardic Jews and Armenians. It is characterized by recurrent episodes of fever, peritonitis, pleuritis, and arthritis. Skin lesions are seen in some patients. Diagnosis of FMF usually is made on clinical grounds only, typically when recurrent attacks of abdominal pain, fever, and arthritis are observed in a patient with an appropriate ethnic background and family history. To date, there are no specific diagnostic laboratory tests for FMF. Three patients with severe recurrent Pyoderma are covered in this report. In all three cases, the cutaneous lesions were associated with clinical manifestations of FMF and responded to colchicine therapy favorably. The importance of such an association and its therapeutic consequences are emphasized. PMID- 1642251 TI - Case report: hypoparathyroidism with menses-associated hypocalcemia. AB - For 18 years, a patient with idiopathic hypoparathyroidism has experienced stiffness or tetany chiefly at the time of menses. A significant decline (0.2 mmol/L) in her serum total and ionized calcium values was observed after the withdrawal of oral contraceptive and after spontaneous onset of menses. No increase in urinary calcium excretion or decline in serum magnesium or calcitriol occurred to explain the fall in serum calcium. In two hypoparathyroid women without the history of menses-associated tetany, serum calcium remained stable after withdrawal of oral contraceptive or conjugated estrogen. Serum calcitriol levels unexpectedly increased in these controls, possibly helping sustain serum calcium. The author concludes the following: (1) some hypoparathyroid women show a significant and symptomatic decline in serum calcium at the time of menses; (2) serum calcium values obtained at the time of menses may not be a reliable guide to adjusting medication dosage for hypoparathyroidism; and (3) further investigation will be needed to determine the mechanism of the decline in serum calcium values and whether the effect of estrogens on serum calcitriol might be altered in the absence of the parathyroid glands. PMID- 1642252 TI - Case report: coronary vasospasm--relation to the hyperthyroid state. AB - While angina is not uncommonly seen in association with hyperthyroidism, only rare case reports have suggested that myocardial ischemia in this state may be due to coronary artery spasm. The authors review the literature and describe a case in which the repetitive occurrence of episodes of myocardial ischemia due to coronary spasm correlated with repeated transient elevations in thyroid hormone levels, thus clarifying this relationship. The importance of defining thyroid status in patients presenting with coronary vasospasm is emphasized and the effects of thyroid hormone on the heart are reviewed. PMID- 1642253 TI - Testosterone deficiency as a risk factor for hip fractures in men: a case-control study. AB - The objective of this study was to determine whether decreased gonadal function is a risk factor for hip fracture in elderly men. The study was a matched case control study performed at an in-hospital orthopedic service at a semi-rural and academic tertiary care center. The patients were seventeen men who presented with hip fractures after simple falls over a 10-month period, 11 men with a history of hip fractures in the preceding 25 months, and 28 randomly selected age-, race-, and living status-matched control subjects (mean age 73 years). Serum pooled total testosterone (9.2 +/- 5.5 nmol/L vs. 12.8 +/- 5.4 nmol/L; p less than 0.02) and free testosterone (37.9 +/- 18.8 pmol/L vs. 48.4 +/- 20.6 pmol/L; p less than 0.03) were significantly lower in hip fracture vs. control patients. Testosterone deficiency was found in 20 (71%) hip fracture men vs. 9 (32%) of the controls (p = 0.003; odds ratio 5.3). Analysis of testosterone values within the stratum of absence of any chronic disorder revealed similar results. Serum 25-hydroxyvitamin D levels were significantly lower in the hip fracture group than in control men (p less than 0.001). The conclusion is that gonadal deficiency appears to be an important and heretofore understudied risk factor for hip fractures in men. Prevention of hip fractures in men may involve early recognition and treatment of testosterone deficiency. PMID- 1642254 TI - Case report: recurrent Salmonella typhi chest wall abscess associated with a pituitary macroadenoma. AB - An unusual manifestation of a Salmonella typhi infection is presented in a patient with a growth hormone producing tumor. Growth hormone may effect cell mediated immunity and predispose to localized or disseminated intracellular infections. PMID- 1642255 TI - Propofol: a review of the pharmacology and applications of an intravenous anesthetic agent. PMID- 1642256 TI - AFCR public policy forum. PMID- 1642257 TI - Current concepts in renovascular hypertension. AB - Renovascular disease represents an important dimension of hypertension. Although estimates vary regarding the exact prevalence of renovascular hypertension, it is being diagnosed with increasing frequency because of refined criteria for the workup and the availability of sensitive diagnostic tests. Two major pathologic entities--atherosclerosis and fibromuscular dysplasia--account for most cases of renovascular hypertension. Once the diagnosis and clinical significance of renal artery stenosis in a hypertensive patient are established, appropriate and specific therapy should be considered. The goal is not only to treat hypertension, but to preserve and restore renal function. Although antihypertensive drug therapy may lower the blood pressure, reperfusion of the kidney (surgical, angioplasty) is a desirable long-term objective in the management of patients with renovascular hypertension. With careful selection of therapeutic choices, we are now able to render optimal care to patients with renovascular hypertension. PMID- 1642258 TI - Is steroid receptor data useful in patients with metastatic breast cancer? AB - Optimal therapy for patients with metastatic breast cancer is unknown. For those with rapidly progressive disease or liver metastases, combination chemotherapy is believed to be the treatment of choice. However, most patients do not fall into that category. For them, two treatment approaches can be considered: (1) ignore estrogen receptor/progesterone receptor (ER/PR) data and treat all patients with hormonal therapy or (2) use ER/PR data and treat patients with ER-/PR- tumors with combination chemotherapy and treat all other patients with hormonal therapy. This report presents a decision analysis for assessing the usefulness of ER/PR data in this situation. The probabilities of response to hormonal therapy were obtained from literature reviews. Patients' utilities or preferences for the various outcomes were estimated by using physicians as patient surrogates. The baseline analysis favored ignoring ER/PR data and treating all patients with hormonal therapy. Extensive sensitivity analyses showed that the decision was most affected by patients' utilities for the various outcomes. The conclusion is that patients' utilities are most important in deciding the usefulness of ER/PR data in metastatic breast cancer. PMID- 1642259 TI - Consanguineous marriage in Jordan. AB - We conducted a population-based study of consanguineous marriages in Jordan. About two thousand households were interviewed. First cousin marriages were encountered in 32.03%, second cousin in 6.8%, distant relation in 10.5%, and no relation in 50% of all marriages, respectively. Inbreeding coefficients were compared with those of other countries. The most important variables affecting inbreeding were social tradition, religion, education, and place of residence- urban vs. rural. Secular trends appear rather stable since the early decades of the twentieth century, especially for first cousin marriages. Jordan society showed a deeply rooted traditional behavioral pattern when inbreeding is considered. PMID- 1642260 TI - Late-onset localized junctional epidermolysis bullosa and mental retardation: a distinct autosomal recessive syndrome. AB - We present 2 sibs with a local junctional type of epidermolysis bullosa associated with enamel defect of the teeth, dystrophic nails of the feet, and mental retardation. Subluxation of the lenses was evident in 1 of them. This combination found in a brother and a sister seems to represent a distinct autosomal recessive type of epidermolysis bullosa. PMID- 1642261 TI - Poland anomaly with a limb body wall disruption defect: case report and review. AB - We describe a female infant with apparent Poland anomaly (PA) and limb body wall defect. Analysis of the defects suggest that a disruption of the lateral embryonic plate mesoderm may have been responsible for the observed lesions. Because of the overlap of this case with PA, we re-examined previous reports of this syndrome. We think that the lesions could be equally well explained as a mesodermal disruption, and point out a previously unrecognised discrepancy between sex and affected side in sporadic PA and inherited PA which supports this view. PMID- 1642262 TI - Dominant syndrome with isolated cryptophthalmos and ocular anomalies. AB - We report on a mother and daughter with nonsyndromal cryptophthalmos. Both patients have additional ocular anomalies, including microphthalmia, retinal dysplasia, and Peters anomaly. The periocular and lid changes seen in these individuals are distinct from those seen in typical cryptophthalmos. The apparent dominant mode of inheritance in this family distinguishes this condition from autosomal recessive isolated cryptophthalmos and from the Fraser or cryptophthalmos syndrome. PMID- 1642263 TI - Pericentric inversion of chromosome 16 in a large kindred: spectrum of morbidity and mortality in offspring. AB - Constitutional pericentric inversions of chromosome 16 are rare in the general population. We report here a large kindred who carry an inv(16)(p13q22) rearrangement. In general, individuals with the inv(16) are in good health but prone to reproductive loss. Two different types of recombinant offspring were identified in this family and analyzed at the molecular level using probes from the alpha-globin and polycystic kidney disease loci. Both were associated with serious major malformations. PMID- 1642264 TI - Platelet dysfunction in a patient with the Opitz (BBBG) syndrome. AB - An 11-year-old girl with Opitz (BBBG) syndrome presented with a bleeding disorder. Studies showed an immune-mediated qualitative platelet dysfunction in the absence of thrombocytopenia. This is the first report of hemostatic dysfunction in a patient with the Opitz (BBBG) syndrome. This report considers the possible relationship of the platelet dysfunction to the Opitz (BBBG) syndrome and its treatment. PMID- 1642265 TI - Basal cell carcinomas, coarse sparse hair, and milia. PMID- 1642266 TI - TAR-like syndrome in a consanguineous Mayan girl. AB - We report on a 3-month-old girl with a TAR-like syndrome. Her older brother died with a similar disorder at 3 months of unknown causes. The parents are second cousins of Mayan ancestry. The infant also had, in addition to the usual abnormalities of TAR syndrome, depressed nasal bridge, cataracts, glaucoma, megalocorneae, and blue sclerae. PMID- 1642267 TI - Aarskog syndrome in a Brazilian boy born to consanguineous parents. AB - We report on a Brazilian boy (F = 1/16) born to consanguineous parents and presenting with typical Aarskog syndrome. Genetic aspects and phenotypic manifestations of this patient are compared with those of the (X-linked) Aarskog syndrome and with the autosomal recessive faciodigitogenital syndrome. PMID- 1642268 TI - Renal tubular dysgenesis: a not uncommon autosomal recessive syndrome: a review. AB - Renal tubular dysgenesis is a recently recognized autosomal recessive condition characterized by short and poorly developed proximal convoluted tubules, leading to oligohydramnios, Potter sequence, and neonatal respiratory failure. We report an additional 9 cases from one pediatric center, suggesting that this syndrome is not as rare as was previously thought. Normal amniotic fluid volumes in affected pregnancies prior to the 22nd week of gestation have been documented, compromising early prenatal diagnosis. Late second trimester sonographic demonstration of oligohydramnios, with structurally normal kidneys, should suggest this diagnosis and the need for detailed post-mortem pathological examination. PMID- 1642269 TI - Neurofibromatosis 1 and osseous fibrous dysplasia in a family. AB - We report on the cosegregation of neurofibromatosis 1 (NF 1) and osseous fibrous dysplasia in a family. The father and 3 children by 2 women are affected. A fourth child had neither NF 1 nor osseous fibrous dysplasia. All 4 affected individuals had NF 1, i.e., cafe-au-lait spots in 4, neurofibromata in 4, Lisch nodules in 3, macrocrania in 3, scoliosis in 2, and curvature of the long bones in 2. Each demonstrated various fibroosseous lesions of the skeleton including non-ossifying fibromas in 3 and both non-ossifying fibromas and fibrous dysplasia in one. This pattern suggests that the fibrous bony lesions are a component of NF 1 in this family. Alternatively, a mutant gene resulting in the fibrous changes in bone could be linked to the gene for NF 1. Another possibility is the coincidence of the 2 non-linked traits segregating in the same family. PMID- 1642270 TI - Chondrodysplasia punctata: a boy with X-linked recessive chondrodysplasia punctata due to an inherited X-Y translocation with a current classification of these disorders. AB - Chondrodysplasia punctata (CDP) is a heterogeneous group of rare bone dysplasias characterized by punctate calcification of cartilage. The punctate calcifications are non-specific and have been seen in a wide variety of disorders including the Zellweger syndrome, warfarin, dilantin, alcohol and rubella embryopathies, vitamin-K-epoxide-reductase deficiency, chromosome trisomies 18 and 21, the Smith Lemli-Opitz syndrome, prenatal infectious chondritis, hypothyroidism, and other rare disorders. We report on a boy with short stature, developmental delay, nasal hypoplasia, telebrachydactyly, hypoplastic genitalia, CDP, ichthyosis, hypoplastic genitalia, and a 46-X,+der(X),t(X;Y)(p22.31;q11.21), Y karyotype. Genomic DNA probe analysis was interpreted as showing that the translocation breakpoint was within the X-linked Kallmann syndrome gene. We review a current classification of these disorders that includes 3 well-defined single gene disorders. These include an autosomal recessive rhizomelic type with early lethality, an X-linked dominant type with presumed male lethality, and an X linked recessive type that has only been described as part of a contiguous gene deletion syndrome. PMID- 1642271 TI - Sparse hair and multiple endocrine disorders in two women heterozygous for adrenoleukodystrophy. AB - We describe two sisters (40 and 42 years old) heterozygous for adrenoleukodystrophy who have multiple endocrine disorders. In addition to the characteristic neurological symptoms, the younger patient has Addison disease and primary hypothyroidism attributable to autoimmune thyroiditis, and the older one has Graves disease. Both patients have loss of body hair and sparse scalp hair, which have not been reported previously in women heterozygous for adrenoleukodystrophy. After the institution of glucocorticoid replacement therapy, the younger sister, who has adrenal insufficiency, has shown unexpected neurological improvement. PMID- 1642272 TI - Combined Goltz and Aicardi syndromes in a terminal Xp deletion: are they a contiguous gene syndrome? AB - We report on 2 girls with a terminal deletion of the short arm of chromosome X. They had microphthalmia, cloudy corneae, mild linear skin lesions, and agenesis of corpus callosum. A comparison of clinical and cytogenetic findings in similar cases suggested that the critical genes for the Goltz and Aicardi syndromes might be contiguous in the region Xp22.31. PMID- 1642273 TI - New mental retardation syndrome with hearing impairment, distinct facial appearance, and skeletal anomalies. AB - We present 2 unrelated children with a distinct pattern of anomalies, including mental retardation, hearing impairment, unusual facial appearance, and skeletal defects. Both children have severe behavior disturbance and hyperactivity. The characteristic facial findings include a broad mouth, broad nasal bridge, mildly anteverted nares with a fleshy nasal tip, and deep nasolabial folds. Skeletal findings include mild to moderate short stature, dysharmonic maturation of epiphyseal ossification centers in the hands, and mild scoliosis. PMID- 1642275 TI - Analysis of sperm chromosome complements from a man heterozygous for a robertsonian translocation 45,XY,t(15q;22q). AB - Chromosome complements were studied in 118 sperm from a man heterozygous for a 15;22 Robertsonian translocation using the human sperm/hamster oocyte fusion technique. Alternate segregation occurred in most spreads (89.6%) and the proportion of normal (42.6%) and balanced complements (47%) was approximately equal. The frequency of sperm that were unbalanced with respect to the translocation was 10.4% and all categories of unbalanced sperm were observed ( 15, -22, +15, +22). The frequency of chromosome abnormalities unrelated to the translocation was 7.6%. Since the frequencies of both numerical (3.4%) and structural abnormalities (3.4%) were within the normal range of control donors, there was no evidence for an interchromosomal effect. The frequencies of X chromosome bearing (48%) and Y-chromosome bearing (52%) sperm were not significantly different from 50%. Data on this translocation were compared to the 4 other reports of cytogenetic analysis in sperm of Robertsonian translocation carriers. PMID- 1642274 TI - Prenatal diagnosis with repetitive in situ hybridization probes. AB - We have used chromosome-specific repetitive sequences to detect the most common human aneuploidies prenatally. Together chromosome 21, 13, 18, X, and Y aneuploidy comprises 95% of the chromosome abnormalities that result in a high risk of abnormal phenotypes at birth. The X, Y, and 18 repetitive probes work reliably in multiple tissue types including directly examined and cultured amniocytes, chorionic villus cells, lymphocytes, and cultured fibroblasts. The probe that detects both chromosomes 13 and 21 routinely gives results in each cell type tested except directly studied amniocytes which can be interpreted in seven-ninths of the cases with protocol 1 and all tested samples with protocol 2. Our protocols diagnosed trisomy 21 in a 23-week fetus with low maternal serum AFP and a trisomy 18 in a direct chorionic villus sample 2 working days after the samples were obtained. Trisomy 21 also has been ruled out in a CVS karyotype first thought to be 47,XY, +21. These studies reflect the potential value of in situ hybridization to provide a more rapid, less expensive means to screen most at-risk fetal populations with less effort in first world cytogenetic laboratories, and to provide economical cytogenetic services in less developed countries. PMID- 1642276 TI - Membranoproliferative glomerulonephritis in a child with Prader-Willi syndrome. AB - We describe a girl with Prader-Willi syndrome and membranoproliferative glomerulonephritis. She had a deletion at 15q11-13. The deletion may have made the child susceptible to renal disease. PMID- 1642277 TI - New distinct lethal osteosclerotic bone dysplasia (Raine syndrome). AB - We report a third case of a rare neonatal lethal sclerotic bone disorder with distinct craniofacial anomalies and striking radiographic and hitherto undescribed histopathologic features. The remarkable similarity between our patient and 2 recently reported infants suggests strongly a distinct entity. We propose the term Raine syndrome as a convenient identification of this disorder. PMID- 1642278 TI - Tyrosinase gene mutations in type I (tyrosinase-deficient) oculocutaneous albinism define two clusters of missense substitutions. AB - Type I (tyrosinase-deficient) oculocutaneous albinism (OCA) results from mutations of the gene encoding tyrosinase, the enzyme that catalyzes the first 2 steps of melanin pigment biosynthesis. In type IA (tyrosinase-negative) OCA tyrosinase enzymatic activity is completely absent, and in type IB ("yellow") OCA tyrosinase activity is greatly reduced. Here, we describe 11 novel mutations of the tyrosinase gene in Caucasian patients with these 2 forms of type I OCA. Type I OCA in Caucasians appears to result from a great variety of different uncommon alleles. More than 80% of the known missense substitutions associated with type I OCA cluster within 2 relatively small regions of the tyrosinase polypeptide, suggesting that these may correspond to functionally important sites within the enzyme. PMID- 1642279 TI - A severe case of mandibuloacral dysplasia in a girl. AB - We report on a 16-year-old girl with mandibuloacral dysplasia, a rare progeroid syndrome. She presented at age 2 years with thin skin on the limbs, characteristic face with prominent eyes, a pinched nose, micrognathia, and small mouth. Hair was sparse and brittle. The terminal phalanges were hypoplastic and showed acroosteolysis. On follow-up, hands and feet showed progressive camptodactyly of fingers and toes with total loss of subcutaneous tissue. The clavicles were hypoplastic. Intelligence was normal. We review the literature on the subject and discuss differential diagnosis. PMID- 1642280 TI - Hypoglossia-hypodactylia syndrome with jejunal atresia in an infant of a diabetic mother. AB - Despite advances in therapy for maternal diabetes, pregnancies of diabetic women remained at an increased risk of spontaneous abortion or delivery of an infant with major malformation. We report on an infant of a diabetic mother with hypoglossia-hypodactylia associated with complete jejunal atresia. A common pathogenesis for these 2 malformations could be a vascular disruptive mechanism with in utero arterial thrombosis. PMID- 1642281 TI - Carrier detection and prenatal diagnosis of X-linked agammaglobulinemia. AB - We investigated the pregnant mother of a boy with X-linked agammaglobulinemia (XLA) but with no family history of immune disease. The X-inactivation pattern was found, using a methylation-sensitive probe, to be skewed in the maternal B cells but random in the polymorphonuclear cells, indicating carrier status and a 50% risk of inheritance for her male fetus. Using probes assigned to regions on either side of the XLA locus and defining RFL polymorphism, we excluded for the first time a diagnosis of XLA on a chorionic villus sample, with a risk of error less than 0.003. Immunological studies performed at the 19th week of gestation and 3 days after birth confirmed normality. Carrier detection based on the X chromosome inactivation pattern, together with prenatal studies using probes close to the disease locus, thus permits prenatal diagnosis in families with isolated cases of XLA. PMID- 1642282 TI - History of C-patient with SC-Roberts/pseudothalidamide syndrome. PMID- 1642283 TI - Congenital heart defect in a Japanese girl with Adams-Oliver syndrome: one of the most important complications. PMID- 1642284 TI - Orofaciodigital syndrome type IV: report of a patient. PMID- 1642286 TI - Uveitis associated with human T-cell lymphotropic virus type I. AB - Seroepidemiologic, clinical, and virologic studies were performed to determine whether human T-cell lymphotropic virus type I was closely associated with uveitis in two hospitals. One hospital was in an endemic area of the virus (Miyakonojo, Miyazaki) and the other hospital was in a less endemic area (Kurume). In the endemic area, the seroprevalence of the virus in patients with uveitis without defined causes (35.4%, 62 of 175 patients) was significantly higher than that in patients with nonuveitic ocular diseases (16.1%, 42 of 261 patients), or in patients with uveitis with defined causes (10.3%, eight of 78 patients). The seroprevalence in younger patients (20 to 49 years of age) with uveitis without defined causes in the area was 44.8% (30 of 67 patients), whereas it was only 9.3% (ten of 107 patients) in the other two groups. A similar observation was recorded even in the less endemic area (Kurume). Because the seroprevalence of the virus in the general population is known to be low in younger patients and to increase with age, these findings were interpreted to indicate that the association of human T-cell lymphotropic virus type I with uveitis was significant. Most patients, particularly those aged 20 through 49 years, had an intermediate uveitis characterized by a moderate inflammation in the vitreous body accompanied by an iritis and retinal vasculitis. The ocular symptoms in the patients differed from those of other types of uveitis common in Japan (Behcet's disease, Vogt-Koyanagi-Harada's disease, and toxoplasmosis, for example).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642287 TI - An unusually high prevalence of ocular toxoplasmosis in southern Brazil. AB - Because of the frequency of ocular toxoplasmosis and its occurrence in multiple siblings in southern Brazil, a population-based household survey was performed to better understand the epidemiologic characteristics of the disease in this region. Of 1,042 individuals examined, 184 (17.7%) were deemed to have ocular toxoplasmosis on the basis of conservative assessment of ophthalmic findings. Of those with ocular toxoplasmosis, 183 (99.5%) had specific IgG antibodies, compared with only 140 of 181 age-matched control subjects (77.4%; P less than .001). The prevalence of ocular toxoplasmosis was 0.9% in 1- to 8-year-olds, 4.3% in 9- to 12-year-olds, 14.3% in 13- to 16-year-olds, and 21.3% (95% confidence interval, 18.6% to 24.2%) in all individuals 13 years or older. The prevalence of ocular toxoplasmosis in this population was more than 30 times higher than previous estimates for the same condition elsewhere. The low prevalence in the young children we studied supplements previous data suggesting that, in this population, ocular toxoplasmosis is a sequela of postnatal rather than congenital infection. PMID- 1642285 TI - A reinvestigation of thirty three fragile(X) families using probe StB12.3. AB - We have reinvestigated 33 fragile X families using probe StB12.3. In 31 families the affected individual showed an insert while in 2 families no insert was detected. The insert fell into two size categories: small (less than 0.5 kb); and large (greater than 0.6 kb) accompanied by methylation of an EagI site. All individuals of either sex having a small insert were fra(X) negative and intellectually normal, while all males having a large insert were fra(X) positive and intellectually impaired. Females having a large insert were either fra(X) positive or negative and either intellectually normal or impaired. No new mutation was found. All daughters of males with a small insert had a small insert; females with a large insert produced males and females who had a large insert, while females with a small insert had offspring with either a large or a small insert. However, females with a small insert tended to fall into one of two categories: either they had only children with a small insert or only children with a large insert, there being only one exception to this rule. We found four unexpected small inserts, two in unrelated spouses and two in female carriers who proved to be compound heterozygotes, indicating that they had inherited an insert from both their parents. These observations suggest that individuals with a small insert must be not uncommon in the general population. PMID- 1642288 TI - X-linked recessive familial exudative vitreoretinopathy. AB - Familial exudative vitreoretinopathy is an inherited disorder characterized by retinal traction, peripheral vitreous opacities, and subretinal and intraretinal exudates. We observed a family in which four boys (the children of three sisters) were affected with this disorder and an X-linked recessive inheritance was apparent. The differential diagnosis includes retinopathy of prematurity, primary hyperplastic primary vitreous, Coats' disease, peripheral uveitis, retinoblastoma, and Norrie's disease, but this differentiation can usually be made on the basis of clinical findings alone. Knowledge of X-linked recessive transmission is important for correct diagnosis and for genetic counseling. PMID- 1642289 TI - Foveal densitometry in adult-onset diffuse drusen. AB - We compared the results of foveal densitometry with results of other retinal function tests in five asymptomatic subjects with adult-onset diffuse drusen. All results of routine retinal function tests, including visual acuity, Rayleigh equation color matches, multiple static perimetry, electroretinography, and electro-oculography, were normal. All five subjects had decreased foveal cone photopigment density with densitometry, indicating an early dysfunction at the level of the foveal cone photoreceptors. Several functional defects may be responsible for the densitometric results in adult-onset diffuse drusen, including retinal pigment epithelium dysfunction, foveal cone photoreceptor misalignment, and a reduction of the in situ foveal cone photopigment. PMID- 1642290 TI - Sudden retinal manifestations of intranasal cocaine and methamphetamine abuse. AB - We examined two patients who had sudden decrease in vision after intranasal cocaine or methamphetamine abuse. A 38-year-old woman with a history of systemic arterial hypertension developed a central retinal artery occlusion four hours after intranasal use of cocaine. A 26-year-old woman had blurred vision and intraretinal hemorrhages shortly after using methamphetamine nasally. The adrenomimetic response and sudden increase in blood pressure associated with the intranasal use of these drugs may have contributed to the retinal vascular manifestations observed in these patients. PMID- 1642291 TI - Clinical and histopathologic changes in the host cornea after epikeratoplasty for keratoconus. AB - Five consecutive patients underwent epikeratoplasty for keratoconus. Postoperatively, four patients had poor visual acuity (average, 20/200) secondary to folds in Descemet's membrane and interface scarring. Two underwent penetrating keratoplasty eight months later. Histopathologic examination of the host corneas and the overlying lenticules disclosed epithelial irregularity and subepithelial fibrosis. The host corneas showed folds in Descemet's membrane and focal posterior stromal fibrosis. Electron microscopy disclosed breaks in Bowman's membrane with irregular collagen, posterior aggregates of amorphous material, and focal endothelial degeneration. The fifth patient had graft ulceration and vascularization that required removal of the lenticule. She underwent a penetrating keratoplasty five months later and histopathologic examination demonstrated persistent folds in Descemet's membrane. Immunostaining of specimens from three cases disclosed a reduced expression of sulfated epitopes of keratan sulfate and an increase in sulfated dermatan sulfate in the lenticule and host corneal tissues. These alterations in stromal proteoglycans are characteristic of stromal scars and keratoconus and provide evidence of pathologic processes in the graft tissue. Because of potential complications, epikeratoplasty should be considered only for those patients who are unsuitable candidates for contact lenses or penetrating keratoplasty. PMID- 1642292 TI - Progression and regression of partial corneal involvement in the iridocorneal endothelial syndrome. AB - We observed three women with partial corneal involvement in the iridocorneal endothelial syndrome for more than ten years. During this time, the peripheral anterior synechiae progressed in all three, with one patient developing glaucoma. In two patients, the abnormal endothelial cells spread to cover the entire posterior corneal surface; in the third, they disappeared almost entirely. The endothelial permeability to fluorescein remained abnormally low only in the two eyes with diffusely abnormal endothelium, and increased to normal in the third eye as the abnormal endothelium disappeared. The permeability in the third eye had been abnormally low only in the superior half of the cornea, where the abnormal endothelium was located. As the abnormal endothelium regressed, it was replaced by normal endothelium with a normal cell density similar to that of the unaffected fellow eye. Thus, for more than ten years, the partial endothelial involvement associated with the iridocorneal endothelial syndrome progressed substantially in two patients and regressed dramatically in a third. PMID- 1642293 TI - Penetrating keratoplasty and transscleral fixation of posterior chamber lens. AB - We reviewed the outcome in 115 patients who underwent penetrating keratoplasty and transscleral fixation of a posterior chamber lens. One patient died soon after surgical procedures, and nine patients were lost to follow-up, leaving a cohort of 105 patients. Mean follow-up time was 26.8 months (range, six to 43 months). Visual acuity of 20/40 or better was found in 29 patients (27.6%) and 20/50 to 20/200 in 37 patients (35.2%). Reasons for poor visual outcome included cystoid macular edema in ten patients (9.5%), age-related macular degeneration in six patients (5.7%), and retinal detachment in four patients (3.8%). None of the patients developed lens decentration. There were no instances of hyphema and only one patient had a perioperative limited suprachoroidal hemorrhage. New-onset increase in intraocular pressure developed in 20 of 66 patients (30.3%). Analysis of the 39 patients with preoperative increase in intraocular pressure that required medical treatment demonstrated an improvement in 13 patients (33.3%), worsening in 12 patients (30.8%), and unchanged status in 14 patients (35.9%). The exposed haptic suture was covered by using one of the following three alternative methods: a conjunctival flap, a scleral flap, or a corneal tissue button. Exposure of the haptic suture through the conjunctiva was a complication in 21 patients (20%). Of these 16 (76.1%) occurred in the group with a conjunctival covering, five (23.8%) occurred in the group with a scleral flap, and none occurred in the corneal tissue button group. This study demonstrated that transscleral fixation of a posterior chamber lens is a viable option in the treatment of patients undergoing penetrating keratoplasty and intraocular lens implantation with absent capsular support. PMID- 1642294 TI - Meibomian gland function and giant papillary conjunctivitis. AB - We examined 42 contact lens-wearing patients for clinical evidence of giant papillary conjunctivitis and for meibomian gland dysfunction with gland dropout. Fifteen patients were free of clinical signs and symptoms of giant papillary conjunctivitis, whereas 27 had clinical symptoms and evidence of giant papillary conjunctivitis. Patients with giant papillary conjunctivitis had significantly more gland dropout with an average of 0.6 +/- 1.2 gland absent in both lower eyelids compared with 0.2 +/- 0.4 gland absent in patients without giant papillary conjunctivitis. Additionally, the viscosity of meibomian gland excreta was greater in the giant papillary conjunctivitis group. There was no difference in tear osmolarity or in the Schirmer test results between the two groups. These results indicated patients with giant papillary conjunctivitis were more likely to have meibomian gland dysfunction with gland dropout than patients without giant papillary conjunctivitis. PMID- 1642295 TI - Spontaneous visual improvement in chiasmal gliomas. AB - Three untreated patients with presumed chiasmal gliomas had spontaneous visual improvement, although serial magnetic resonance imaging in two of the patients showed the lesions to be unchanged. Two patients had evidence of neurofibromatosis. Three other patients with similar disease courses have been documented in the medical literature. These cases demonstrate that conservative management of optic chiasmal gliomas may sometimes be associated with favorable outcomes. PMID- 1642296 TI - Nucleolar organizer regions in iris nevi and melanomas. AB - The silver staining of nucleolar organizer region-associated proteins is an objective method that has been used to differentiate benign from malignant neoplasms. Recently this method was used to distinguish benign choroidal nevi from malignant choroidal melanomas. We studied 24 iris melanocytic lesions to assess the applicability of this technique for differentiating benign from neoplastic iris tumors. Masked observers determined the number of silver-stained nucleolar organizer region dots per cell for silver-stained specimens. Iris nevi contained a mean of 1.6 silver-stained nucleolar organizer region dots per cell, whereas iris (spindle A and B, spindle B, epithelioid, mixed cell) malignant melanomas contained a mean of at least 3.5 silver-stained nucleolar organizer region dots per cell (P less than .0001). All iris nevi demonstrated counts lower than 1.9, whereas all iris melanomas demonstrated counts greater than 2.8. Silver stained nucleolar organizer region counts were also compared with the clinicopathologic variables of gender, age, and largest specimen dimension. Only the largest specimen dimension correlated with silver-stained nucleolar organizer region counts (P less than .0029). The silver-stained nucleolar organizer region method is a simple technique for differentiating iris nevi from iris melanomas. The silver-stained nucleolar organizer region technique may aid in the assessment and treatment of iris lesions by confirming the malignancy of biopsy specimens. PMID- 1642297 TI - Adjunctive hyperbaric oxygen in the treatment of bilateral cerebro-rhino-orbital mucormycosis. AB - Survival is uncommon in bilateral cerebro-rhino-orbital mucormycosis treated surgically and medically. A 66-year-old man in previously good health had bilateral cerebro-rhino-orbital mucormycosis and newly diagnosed nonketotic diabetes mellitus at initial examination. Total loss of vision, proptosis, and ophthalmoplegia of both eyes were present. The patient was treated with aggressive surgical and medical therapies that included bilateral orbital exenteration, intravenous and local amphotericin B, hyperbaric oxygen, and control of the diabetes mellitus. One and one-half years after onset of the illness, the patient is alert and clinically stable. The importance of prompt diagnosis and aggressive treatment of this disease is emphasized by this case. Additionally, we suggest that adjunctive hyperbaric oxygen is a reasonable modality in the treatment of this often fatal disease. PMID- 1642298 TI - The solubility of antibiotic and corticosteroid combinations. AB - The use of collagen shields soaked in various combinations of medications has been advocated to enhance drug delivery to the cornea. Recently, severe corneal toxicity associated with aggregate formation in mixtures of gentamicin and methylprednisolone prompted our study of the effect of drug concentration, pH, and temperature on the solubility of several antibiotic and corticosteroid formulations commonly used to treat ocular disease. Selected combinations of cefazolin, vancomycin, tobramycin, gentamicin, methylprednisolone, and dexamethasone were evaluated. Mixtures of tobramycin and vancomycin produced no precipitates, but many spheroid aggregates were seen when methylprednisolone and gentamicin were combined. Although the effects of precipitate formation on drug bioavailability and toxicity have not been fully determined, until such information is available, the use of combinations of drugs that remain in solution during administration is recommended. PMID- 1642299 TI - Histologic study of healing after ab interno laser sclerostomy. AB - We examined the histologic characteristics of healing after ab interno laser sclerostomy in a human eye. A KTP 532 green laser coupled to a 300-microns quartz fiberoptic probe was used to create an ab interno sclerostomy in a terminally ill patient with pigmentary glaucoma. The intraocular pressure increased five days postoperatively and did not respond to medical treatment. The patient died six weeks postoperatively of metastatic lung cancer. Histopathologic analysis showed a patent 150-microns scleral lumen from the anterior chamber to the episclera, surrounded by a 300-microns zone of acellular thermal damage. There was no healing of the lumen. The subconjunctival end of the lumen was capped with a thick episcleral scar, which caused the failure of the operation. PMID- 1642300 TI - The obligation of ophthalmic organizations to report their actions. PMID- 1642301 TI - Closure of fornix-based posttrabeculectomy conjunctival wound leaks with autologous fibrin glue. PMID- 1642302 TI - Mucogenic glaucoma caused by an epithelial cyst of the iris stroma. PMID- 1642303 TI - Central retinal artery occlusion after neck irradiation. PMID- 1642304 TI - Traumatic rupture of a persistent hyaloid artery. PMID- 1642305 TI - Calcified intraocular abscess simulating retinoblastoma. PMID- 1642306 TI - Use of a transparent film dressing to enhance compliance with occlusion therapy for amblyopia. PMID- 1642307 TI - Ocular complications in Sweet's syndrome. PMID- 1642308 TI - Recurrence of herpetic stromal keratitis after a conjunctival flap surgical procedure. PMID- 1642309 TI - Enterococcus faecalis infection in a corneal graft. PMID- 1642310 TI - Keratoconjunctivitis sicca in a patient with a Jones tube to treat sleep apnea. PMID- 1642311 TI - Central retinal artery occlusion after varicella. PMID- 1642312 TI - Controversies in the management of retinopathy of prematurity. PMID- 1642313 TI - Torsional diplopia after transantral orbital decompression and extraocular muscle surgery associated with Graves' orbitopathy. PMID- 1642314 TI - Running nylon suture dissolution after penetrating keratoplasty. PMID- 1642315 TI - Positional behavior and body size of arboreal primates: a theoretical framework for field studies and an illustration of its application. AB - The rationale for most field studies of the positional behavior of arboreal primates has been the need to document natural behaviors quantitatively in order to infer the functional significance of morphological configurations. This focus on interactions of morphology with behavior is justifiable, but there exists another important level of biological relationships, that of the animal with its structural habitat, which it must negotiate to find food and avoid being preyed on. Recently it has become apparent that body size is likely to affect relationships of positional behavior with habitat structure, as well as with morphology. Here I offer a framework for research on functional relationships of positional behavior, body size, and habitat structure, with the ultimate objective of elucidating the aptive significance of the great diversity exhibited by arboreal primates. This approach specifies several distinct problems that animals solve, and indicates how research might be directed at revealing the relative effectiveness with which different primates solve them. A preliminary application of the framework examines sympatric north Sumatran primates. PMID- 1642316 TI - Genetic and environmental contributions to the variance of body height in a sample of first and second degree relatives. AB - Height was measured in a health screening of the population in Nord-Trondelag, Norway. Correlations were computed for 24,281 pairs of spouses, 43,613 pairs of parents and offspring, 19,168 pairs of siblings, 1,318 pairs of grandparents and grandchildren, 1,218 cognate avuncular pairs, 849 noncognate avuncular pairs, 175 pairs of same-sexed twins, and smaller groups of other types of relatives. Fitting of structural equation models showed proportions of additive genetic variance of approximately 0.8 for both sexes and small sex-specific effects that probably reflect genetic dominance or environmental sibling effects. The correlations between parents and offspring were significantly lower in old than young cohorts, seeming to imply some kind of interaction effect between genes and environment. PMID- 1642317 TI - Bantu beta s cluster haplotype predominates among Brazilian blacks. AB - We describe the combination of polymorphic restriction-enzyme sites in the beta globin gene cluster (haplotypes) for 74 chromosomes from Brazilian Blacks bearing the sickle hemoglobin gene (beta s). The three most common African beta s haplotypes account for 67 chromosomes: 49/74 (66.2%) were identified as Central African Republic (CAR or Bantu) type, 17 (23.0%) as Benin, and one as Senegal; seven chromosomes (9.5%) had minor atypical haplotypes. This distribution is different from that observed in the United States or Jamaica, where the Benin haplotype predominates, and results from different patterns of slave trades to North and South Americas. Since the beta s gene cluster polymorphisms modulate the severity of sickle cell anemia, this heterogeneity may explain differences of the clinical behavior of the disease in the United States and South America, and should also be considered in relation to other features and diseases. PMID- 1642318 TI - Effects of demographic and ethnohistorical factors on average heterozygosities of South Amerindians. AB - Recent investigations have shown that average within-Tupi genetic distances differ from within-Carib distances, which is possibly due to differences in effective size of the populations belonging to these two linguistic stocks of South American tribes. The aim of this paper is to verify the influence of demographic factors and of interpopulation contacts on the degree of intragroup genetic variability of 18 South American native groups (eight Carib, seven Tupi, and three Ge). The mean per locus per individual heterozygosity (Hm) was studied for seven polymorphic systems and the distance from the centroid rii on Hm was evaluated with regression analysis according to Harpending and Ward's model. Data on intergroup contacts among the populations since the end of the eighteenth century were collected from an extensive review of the ethnohistorical literature. The level of Hm of the three linguistic stocks did not differ, which suggests a homogeneous within-group variation for these groups. In addition, there was no association between gene diversity and population size. On the other hand, demographic size correlated with rii, which suggest that gene frequencies in groups of larger populations more closely resemble the average gene frequencies of native South Americans. Values of rii differed between the stocks, and the average distance from the centroid of the Carib was about 2.6 times greater than that of the Tupi, in accordance with previous genetic distance analysis. It should also be emphasized that there was an important correlation between mean heterozygosity and the degree of historical intertribal contacts. This constitutes a particularly significant finding, suggesting the basic role of intertribal gene flow of the past two centuries on the level of present genetic variability of South American tribes. PMID- 1642319 TI - Nutritional status of adults in rural Mali. AB - An anthropometric assessment was conducted of 441 adults from six rural villages in southern Mali. As is typical for human populations, females are shorter and lighter than males. Both females (N = 320) and males (N = 121) are shorter and lighter than their U.S. counterparts. Mean weight in the sample is 53.4 +/- 8.5 kilos for females and 58.8 +/- 6.5 kilos for males. Mean height is 160.4 +/- 5.7 cm for females and 171.3 +/- 6.6 cm for males. The data for height in males are very similar to those reported from other surveys in Mali, and show no evidence for a positive secular trend in height. Mean body mass index (BMI) is 20.8 for females and 20.0 for males. These are lower than U.S. averages, but well above suggested cutoff points for malnutrition in adults. Average arm circumference is 26.5 cm for females and 26.4 cm for males. Females have relatively large arm circumferences due, in part, to the heavy manual labor they perform. Average head circumference is 53.0 cm for females and 54.8 cm for males. For both sexes, these values are more than 1 standard deviation (SD) below the U.S. means. Adult values for anthropometric measurements reflect childhood stresses of malnutrition and disease, and a lifetime of accommodation to a high-carbohydrate, low-protein diet, and hard physical labor. Females are significantly closer to the U.S. standards than males for weight, height, BMI, and arm circumference; these findings support the idea that females are buffered from environmental stresses relative to males. In addition, females exhibit significantly more variability than males for weight, arm circumference, and head circumference, but not for height, suggesting that variability in adult height does not reflect the presence or absence of female buffering or the level of environmental adversity. PMID- 1642320 TI - Effects of fronto-occipital artificial cranial vault modification on the cranial base and face. AB - Artificial reshaping of the cranial vault has been practiced by many human groups and provides a natural experiment in which the relationships of neurocranial, cranial base, and facial growth can be investigated. We test the hypothesis that fronto-occipital artificial reshaping of the neurocranial vault results in specific changes in the cranial base and face. Fronto-occipital reshaping results from the application of pads or a cradle board which constrains cranial vault growth, limiting growth between the frontal and occipital and allowing compensatory growth of the parietals in a mediolateral direction. Two skeletal series including both normal and artificially modified crania are analyzed, a prehistoric Peruvian Ancon sample (47 normal, 64 modified crania) and a Songish Indian sample from British Columbia (6 normal, 4 modified). Three-dimensional coordinates of 53 landmarks were measured with a diagraph and used to form 9 finite elements as a prelude to finite element scaling analysis. Finite element scaling was used to compare average normal and modified crania and the results were evaluated for statistical significance using a bootstrap test. Fronto occipitally reshaped Ancon crania are significantly different from normal in the vault, cranial base, and face. The vault is compressed along an anterior-superior to posterior-inferior axis and expanded along a mediolateral axis in modified individuals. The cranial base is wider and shallower in the modified crania and the face is foreshortened and wider with the anterior orbital rim moving inferior and posterior towards the cranial base. The Songish crania display a different modification of the vault and face, indicating that important differences may exist in the morphological effects of fronto-occipital reshaping from one group to another. PMID- 1642321 TI - Dental microwear and diet in Venezuelan primates. AB - Recent microwear analyses have demonstrated that wear patterns can be correlated with dietary differences. However, much of this work has been based on analyses of museum material where dates and locations of collection are not well known. In view of these difficulties, it would be desirable to compare microwear patterns for different genera collected from the same area at the same time. The opportunity to do this was provided by the collections of the Smithsonian Venezuelan Project (Handley, 1976), in which multiple primate genera were collected from the same humid tropical forest sites within the same month. The monkeys represent a wide range of dietary preferences, and include Saimiri, Cebus, Chiropotes, Ateles, Aotus, Pithecia, and Alouatta. As in previous microwear analyses, epoxy replicas were prepared from dental impressions, as described by Rose (1983) and Teaford and Oyen (1989). Two micrographs were taken of facet 9 on an upper second molar of each specimen. Computations and analyses were the same as described by Teaford and Robinson (1989). Results reaffirm previously documented differences in dental microwear between primates that feed on hard objects versus those that do not--with Pithecia and Alouatta at the extremes of a range of microwear patterns including more subtle differences between species with intermediate diets. The subtle microwear differences are by no means easy to document in museum samples. However, additional results suggest that 1) the width of microscopic scratches may be a poor indicator of dietary differences, 2) large and small pits may be formed differently, and 3) there are very few seasonal differences in dental microwear in the primates at these humid tropical forest sites. PMID- 1642322 TI - Muscle force recruitment and biomechanical modeling: an analysis of masseter muscle function during mastication in Macaca fascicularis. AB - The main purpose of this study is to test the hypothesis that as subjects chew with increasing levels of force, the ratio of the working- to balancing-side jaw muscle force (W/B) decreases and begins to approach 1.0. We did this by analyzing relative masseter force in Macaca fascicularis using both strain gage and surface electromyographic (EMG) techniques. In addition, we also analyzed: 1) the relationship between jaw position using cineradiographic techniques and relative masseter force, 2) the timing differences between relative masseter force from the working and balancing sides, and 3) the loading and unloading characteristics of the masseter muscle. Our findings indicate that when macaques increase the amount of overall masticatory force during chewing, the W/B ratio for masseter force frequently (but not always) decreases and begins to approach 1.0. Therefore, our working hypothesis is not completely supported because the W/B ratio does not decrease with increasing levels of force in all subjects. The data also demonstrate timing differences in masseter force. During apple-skin mastication, the average peak masseter force on the working side occurs immediately at or slightly after the initial occurrence of maximum intercuspation, whereas the average peak masseter force on the balancing side occurs well before maximum intercuspation. On average, we found that peak force from the balancing-side masseter precedes the working-side masseter by about 26 msec. The greater the asynchrony between working- and balancing-side masseter force, the greater the difference in the relative magnitude of these forces. For example, in the subject with the greatest asynchrony, the balancing-side masseter had already fallen to about one-half of peak force when the working-side masseter reached peak force. Our data also indicate that the loading and unloading characteristics of the masseter differ between the working and balancing sides. Loading (from 50 to 100% of peak force) and unloading (from 100 to 50% of peak force) for the balancing-side masseter tends to be rather symmetrical. In contrast, the working-side masseter takes much longer to load from 50 to 100% of peak force than it does to unload from 100 to 50% of peak force. Finally, it takes on average about 35 msec for the working-side zygoma and 42 msec for the balancing-side zygoma to unload from 100 to 50% of peak force during apple-skin mastication, indicating that the unloading characteristics of the macaque masseter during mastication closely approximates its relaxation characteristics (as determined by muscle stimulation). PMID- 1642323 TI - Erosive arthritis and spondyloarthropathy in Old World primates. AB - Presence of spine and sacroiliac involvement and the nature and distribution of the erosive lesions allow definitive diagnosis of spondyloarthropathy. Thus, spondyloarthropathy was identified in Theropithecus, Papio, Cercopithecus, Macaca, Colobus, Presbytis, and Hylobates. Only monarticular erosive disease was present in prosimians, precluding a diagnosis of spondyloarthropathy for that group. The distribution of erosive disease and axial joint involvement in 1,349 non-prosimian Old World primates is quite characteristic of that noted in human psoriatic arthritis. While Reiter's syndrome must also be considered, the histologic appearance of skin lesions in Macaca is characteristic of psoriasis. Evidence of spondyloarthropathy abounds in the literature of primate skeletal disease. Environmentally based contagions may be important in the pathophysiology of spondyloarthropathy. The wide geographic distribution of the phenomena in monkeys suggests a "panendemic," with limited individual susceptibility (compared to that noted in gorillas and chimpanzees). Identical occurrence of erosive arthritis/spondyloarthropathy in free-ranging and artificially restrained animals suggests that spondyloarthropathy can validly be studied in artificially restrained populations. This perspective should allow application of human therapeutic approaches to and perhaps improve the quality of life for artificially restrained, afflicted individuals. PMID- 1642324 TI - Laryngeal edema induced by neck dissection and catheter thrombosis. AB - PURPOSE: There are many possible causes of airway edema in a patient being treated for squamous cell carcinoma of the head and neck. The differential diagnosis includes radiation changes, anaphylaxis, and venous or lymphatic obstruction secondary to mechanical compromise resulting from infection, recurrent tumor, or anatomic distortion. METHODS: A 60-year-old man underwent partial glossectomy and right radical neck dissection for squamous cell carcinoma of the tongue. He subsequently required insertion of a Hickman catheter for administration of chemotherapy to treat recurrent disease. Edema of the left neck, shoulder, and arm was noted to accompany the onset of laryngeal obstruction secondary to supraglottic edema. RESULTS: Catheter-induced thrombosis of the left brachycephalic vein obstructed the only residual jugular vein and was responsible for the sudden airway obstruction. CONCLUSION: Acute laryngeal edema may be caused by obstruction of venous outflow. Invasive catheters should be placed with caution in patients who have undergone surgical sacrifice of the contralateral internal jugular vein. PMID- 1642325 TI - Augmentation genioplasty: when bone is not enough. AB - PURPOSE: Augmentation genioplasty is indicated to correct microgenia. When a large defect must be corrected, the additional use of a soft alloplastic implant may be indicated. METHODS: A 22-year-old patient is presented who required correction of microgenia. A 15-mm advancement of the chin was required to obtain an acceptable cosmetic result. RESULTS: An augmentation genioplasty achieved an 8 mm correction. This was supplemented by a silicone gel-filled implant inserted subperiosteally. This resulted in an outstanding cosmetic result. CONCLUSIONS: Chin contour is an important aspect of facial aesthetics. The sliding genioplasty is ideally suited for correcting most chin deformities; however, the insertion of an alloplast may augment patients with severe microgenia. Avoidance of the donor site morbidity associated with the use of autogenous bone is a major benefit of this procedure. PMID- 1642327 TI - Pneumolabyrinth: a computed tomographic sign of temporal bone fracture. PMID- 1642326 TI - Malignant salivary gland tumors: squamous cell carcinoma of the submandibular gland in a child. AB - PURPOSE: Malignant neoplasms of the salivary glands are extremely unusual in the pediatric age group. METHODS: We report an 11-year-old boy who presented with a mass in the left submandibular region and a second mass in the jugularfacial venous angle. RESULTS: Histologic evaluation determined that this was a squamous cell carcinoma of the submandibular gland with metastasis to a cervical node. Review of the literature was undertaken to identify the rate of malignant salivary gland tumors in children. Malignant salivary gland tumors are extremely rare in children. When malignancy does occur, nearly 90% are present in the parotid gland. The submandibular gland is effected in 7.7% of cases. The most common malignancy in salivary glands of children is the mucoepidermoid carcinoma. Squamous cell carcinoma occurs in less than 2% of cases. CONCLUSIONS: Salivary gland tumors are very rare in children in contrast to adults. The proportion of malignant tumors in children is higher than that observed in adults; however, it is not possible to draw conclusions concerning treatment from the few case reports that exist. A higher rate of local recurrence and cervical lymph node metastasis may be expected in children. PMID- 1642328 TI - Pediatric tracheotomy: a review of technique. PMID- 1642329 TI - Subjective idiopathic tinnitus: a unified plan of management. PMID- 1642330 TI - Laryngeal transplantation: ethical considerations. PMID- 1642331 TI - The management of congenital neck masses. PMID- 1642332 TI - Developmental anatomy of the eustachian tube and middle ear in mice. AB - PURPOSE: It is generally accepted that the development of the tubotympanum has significant bearing on the susceptibility to ear infection. A detailed study of the differentiation of ciliated cells in secretory elements will be useful in understanding both the normal physiology and the pathology of the tubotympanum. METHOD: Serially sectioned temporal bones of 76 mice ranging from gestational age day 11 to postnatal day 21 were examined microscopically. RESULTS: During the period of gestation, the tubotympanic recess was formed at the 12th day and began to extend to form the middle ear between the 13th and 14th days. A rapid increase in the volume of the tubotympanic recess was observed between the 15th and 16th days when a definitive division of the tubotympanic recess into the eustachian tube and middle ear cavity was observed. Postnatally the tubotympanum attained an adult form around day 9, and the maximum change of middle ear volume was noted on day 11, when the mesenchymal tissue in the middle ear cavity disappeared completely. Development of the ciliated cells was observed concurrently in both the eustachian tube and middle ear on the 16th gestational day, one day earlier than the appearance of the epithelial secretory cells in both the eustachian tube and middle ear. The number of ciliated cells and secretory cells increased rapidly after birth. Tubal glands were well developed with evidence of secretory activity around the time of birth. CONCLUSIONS: Based on these findings, one can conclude that the mucociliary defense system starts to develop during the fetal stage and is well established immediately after birth. PMID- 1642333 TI - Morphology and functions of the human seminal vesicle. AB - The seminal vesicles originate in embryos of about 58 mm crown-rump-length from the Wolffian duct under the influence of testosterone. Along with the ampulla of the vas deferens and the ejaculatory duct, they form a functional unit that develops slowly until the onset of puberty. Developmental malformations occur as uni- or bilateral agenesis, aplasia, cysts, or ureterovesicular fistules. After puberty, the glands form sac-like structures which have a capacity of about 3.4 4.5 ccm and contribute about 70% of the seminal fluid. In addition to secretion, they are capable of reabsorption of fluids or dissolved substances, and of spermatophagy (ingestion and degradation of damaged spermatozoa by epithelial cells). Secretory activity of the glands is a measure of testosterone supplementation to the epithelium. Nervous regulation of secretion is realized by cholinergic post-ganglionic, sympathetic (and perhaps parasympathetic) fibres, derived from pelvic plexus. Contraction of the muscular wall occurs under the influence of excitatory adrenergic and modulatory NPY-encephalin-peptidergic nerve fibres. The secretory products of the seminal vesicles encompass (1) ions (K+: 1.1 mM ml-1) (2) low molecular weight substances (fructose: above 1.2 mg ml 1; prostaglandins above 250 microliters ml-1, (3) peptides (endorphin: 330 pg ml 1), and (4) proteins. In addition to plasma protein related forms such as transferrin, lactoferrin, and fibronectin, specific proteins such as semenogelin (52 kDa) are synthesized, the scaffold protein of semen coagulate forming the substrate for PSA (prostate specific antigen), sperm motility inhibitor (ca. 18 kDa), and others (placental protein 5, protein kinase inhibitor, carboanhydrase, 5'-nucleotidase), some of which are immunosuppressive. Therefore, functions of the seminal vesicles concern (a) formation of seminal coagulum, (b) modification of sperm functions (motility, capacitation), and (c) immunosuppression. Additional functions within the female genital system, perhaps during pre implantation period, are likely, but remain to be proven experimentally. PMID- 1642334 TI - Leucocyte populations in semen and male accessory gland function: relationship with antisperm antibodies and seminal quality. AB - Semen samples from 279 infertility patients attending an Immunological Centre were analysed to evaluate the relationship between the populations of leucocytes, seminal quality, antisperm antibodies, and seminal vesicle function. The most frequent finding between leucocytospermic samples was asthenozoospermia (57%), whereas in non-leucocytospermic samples normozoospermia was the most frequent finding (47%). In the samples with asthenozoospermia, granulocytes predominated, whereas in those with oligozoospermia and azoospermia a reduction in the number of macrophages and lymphocytes was observed, suggesting an obstructive process at the level of epididymis and/or vas deferens where these leucocytes are mostly produced. In the case of hypofunction of the seminal vesicles there was a predominance in granulocytes. The increased levels of each type of leucocytes affected seminal quality only when seminal vesicles were affected. Only the elevated granulocytes count was related to a decrease in sperm motility. In those samples with leucocytospermia, positive antisperm antibodies (ASA) were associated with low sperm motility, low sperm normal morphology, and low value of seminal corrected fructose, whereas, in the absence of leucocytospermia, ASA, were more related to low sperm counts. These data suggest that granulocytes were more related to seminal vesicles dysfunction and sperm motility changes, and that ASA may be observed in the presence or absence of leucocytospermia. PMID- 1642335 TI - The concentration pattern of laminin, hyaluronan, and aminoterminal propeptide of type III procollagen in seminal fluid. AB - The extracellular matrix components laminin, N-terminal propeptide of type III procollagen (PIIINP) and hyaluronan (HA) were determined in seminal fluids of 119 patients submitted for diagnosis of infertility. The concentrations of laminin and HA, but not those of PIIINP, were elevated in seminal fluid in comparison to their ranges of concentration in normal sera. Only weak correlations were observed between the concentrations of the three matrix components. The concentration of HA was negatively correlated with sperm count and ejaculate volume. Laminin was positively correlated with sperm count, the age of patients, and highly significantly with the concentrations of acrosin. A highly significant positive correlation was also found between PIIINP and fructose. By analysis of variance it could be shown that patients with azoospermia and oligozoospermia have significantly higher levels of HA than those with normospermia. Patients with terato- and asthenozoospermia showed no characteristic pattern of the matrix components. PMID- 1642336 TI - Evaluation of the hypo-osmotic swelling test in relation with advanced methods of semen analysis. AB - The hypo-osmotic swelling test was claimed to assess an independent functional characteristic of human spermatozoa bearing relevance to their fertilizing capacity. To test this claim, we have studied the relationship between the result of the hypo-osmotic swelling test with that of conventional semen analysis and sperm motility patterns, the semen content of adenosine triphosphate, the staining pattern to acidified aniline blue, and the zona-free hamster oocyte test. The result of the HOS test is significantly correlated with all sperm characteristics except for the aniline blue stainability and the hamster oocyte test. The capacity of spermatozoa to react in a hypo-osmotic environment expresses the same functional information as the viability test using eosine staining. It is concluded that the hypo-osmotic swelling test does not add relevant information to that obtained by routine sperm analysis with regards to the fertilizing potential of semen. PMID- 1642337 TI - S-100 protein immunoreactivity in bovine testis. AB - The present study deals with immunohistochemical localization of S-100 protein in the bovine testis. Immunoreactivity for the protein was seen in Sertoli cells of the seminiferous tubules and as a particularly intense staining in the terminal tubular segment (transitional region, middle portion, and terminal plug), which is mainly composed of modified Sertoli cells. Immunoreactivity was also found in epithelial cells of the straight testicular tubules and rete testis, and in the endothelium of capillaries, veins and lymphatic vessels. Although the functional significance of S-100 protein immunoreactivity in the Sertoli cells remains unclear, the present results suggest that it may be involved in the microtubule assembly-disassembly system. The specificity of the immunolabelling observed should enable the antigen and/or antibody to S-100 to be used as an investigative and diagnostic tool in the study of bovine Sertoli cell function. PMID- 1642338 TI - Fluorescence body of bovine spermatozoa represents Y-chromosome. AB - The fluorescence body test would be an inexpensive method of quantifying the Y chromosomes of mammalian spermatozoa, and could be used to monitor the enrichment of X- and Y-spermatozoa. However, a definitive proof that the fluorescence bodies are markers of the Y-chromosome, is available only for humans and gorillas. In the study described here it is demonstrated for the first time in cattle that the fluorescence bodies of spermatozoa represent the Y-chromosomes. The evidence is furnished by a combination of the fluorescence staining (quinacrine mustard) with the in-situ-hybridization using bovine male-specific DNA fragments. The incidence of f-bodies corresponded with autoradiographic grains caused by the tritiated Y specific DNA in the examined 144 single cells (75, 5, and 88% agreement). PMID- 1642339 TI - Latex anaphylaxis. PMID- 1642340 TI - Thiopental pharmacodynamics. I. Defining the pseudo-steady-state serum concentration-EEG effect relationship. AB - To assess depth of anesthesia for intravenous anesthetics using clinical stimuli and observed responses, it is necessary to achieve constant serum concentrations of drug that result in constant biophase or central nervous system concentrations. The goal of this investigation was to use a computer-controlled infusion pump (CCIP) to obtain constant serum thiopental concentrations and use the electroencephalogram (EEG) as a measure of thiopental's central nervous system drug effect. The number of waves per second obtained from aperiodic waveform analysis was used as the EEG measure. A CCIP was used in six male volunteers to attain rapidly and then maintain for 6-min time periods the following pseudo-steady-state constant serum thiopental target concentrations: 10, 20, 30, and 40 micrograms/ml. The median performance error (bias) of the CCIP using 149 measurements of thiopental serum concentrations in six subjects was +5%, and the median absolute performance error (accuracy) was 16%. Following the step change in serum thiopental concentration, the EEG number of waves per second stabilized within 2-3 min and the remained constant until the target serum thiopental concentration was changed. When the constant serum thiopental concentration was plotted against the number of waves per second for each subject, a biphasic serum concentration versus EEG effect relationship was seen. This biphasic concentration:response relationship was characterized with a nonparametric pharmacodynamic model. The awake, baseline EEG was 10.6 waves/s; at peak activation the EEG was 19.1 waves/s and occurred at a serum thiopental concentration of 13.3 micrograms/ml. At a serum thiopental concentration of 31.2 micrograms/ml the EEG had slowed to 10.6 waves/s (back to baseline) and at 41.2 micrograms/ml was 50% below the baseline, awake value. Zero waves per second occurred at serum thiopental concentrations greater than 50 micrograms/ml. Using a CCIP it is possible to establish constant serum thiopental concentration rapidly and characterize the concentration versus EEG drug effect relationship. PMID- 1642341 TI - Thiopental pharmacodynamics. II. Quantitation of clinical and electroencephalographic depth of anesthesia. AB - This study examined the relationship among pseudo-steady-state (constant) serum thiopental concentrations, clinical anesthetic depth as assessed by several perioperative stimuli, and the electroencephalogram (EEG). Twenty-six ASA physical status 1 or 2 patients participated in the study. Two constant serum thiopental concentrations were maintained in each patient using a computer controlled infusion pump. The first randomly assigned target serum concentration of 10-30 micrograms/ml was maintained for 5 min to allow serum:brain equilibration. Then the following stimuli were applied at 1-min intervals: verbal command, tetanic nerve stimulation, trapezius muscle squeeze, and laryngoscopy. A second, higher, randomly assigned target serum concentration of 40-90 micrograms/ml was then achieved and maintained by the computer-controlled infusion pump. The previously described stimuli were reapplied, after which laryngoscopy and intubation was performed. A positive response was recorded if purposeful extremity movement or coughing was observed. Using the quantal movement or cough response and the measured constant serum thiopental concentration, the probability of no movement to each stimulus was characterized using logistic regression. The serum thiopental concentrations that produced a 50% probability of no movement response for the clinical stimuli were as follows: 15.6 micrograms/ml for verbal command, 30.3 micrograms/ml for tetanic nerve stimulation, 39.8 micrograms/ml for trapezius muscle squeeze, 50.7 micrograms/ml for laryngoscopy, and 78.8 micrograms/ml for laryngoscopy followed by intubation. The EEG was analyzed using aperiodic waveform analysis to derive the number of waves per second. A biphasic relationship between constant serum thiopental concentration and the EEG number of waves per second was observed. Loss of responsiveness to verbal stimulation occurred when the EEG was activated at 15-18 waves/s.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642342 TI - Evaluation of risk factors for laryngeal edema after tracheal extubation in adults and its prevention by dexamethasone. A placebo-controlled, double-blind, multicenter study. AB - Because laryngeal edema (LE) after tracheal extubation is likely to result from an exudative response, corticosteroids often are given routinely as a preventive treatment. No adequate controlled study supports this strategy, however. A prospective, randomized, placebo-controlled, double-blind, multicenter trial that included 700 consecutive patients requiring tracheal intubation and mechanical ventilation was conducted to determine risk factors for LE occurrence after tracheal extubation in adults and to evaluate the efficacy of corticosteroids in its prevention. One hour before extubation, patients were given either an intravenous bolus of 8 mg dexamethasone or a placebo. Patients were divided into two groups: 1) those in whom short-duration intubation (SDI, less than 36 h) was administered; and 2) those in whom long-duration intubation (LDI, more than 36 h) was administered. Minor LE was diagnosed when either stridor or laryngeal dyspnea, or both, occurred; major LE was diagnosed when reintubation due to LE was required, with LE evidenced during direct laryngoscopy. The overall incidence of LE was 4.2% and varied among the six participating centers from 2.3 to 6.9% (not significant). In only seven patients (1%), all with LDI, was tracheal reintubation required for LE. Laryngeal edema occurred more frequently after LDI than after SDI (7.2 vs. 0.9%; P less than 0.001). It also was more frequent in female than in male patients (20/284 vs. 8/379; P less than 0.05), irrespective of intubation duration and treatment. There was no association between LE and either difficulty/route of intubation or admission diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642343 TI - Epidural versus general anesthesia, ambient operating room temperature, and patient age as predictors of inadvertent hypothermia. AB - To elucidate the multifactorial nature of perioperative changes in body temperature, the influence of several clinical variables, including anesthetic technique, ambient operating room temperature, and age, were evaluated. Perioperative oral sublingual temperatures were measured in 97 patients undergoing lower extremity vascular surgery randomized to receive either general (GA) or epidural (EA) anesthesia. Surgery and anesthesia were performed in operating rooms (OR) with a relatively warm mean ambient temperature (24.5 +/- 0.4 degrees C) (GA, n = 30; EA, n = 33) or relatively cold mean ambient temperature (21.3 +/- 0.3 degrees C) (GA, n = 21; EA, n = 13). Patients were 35 94 yr old, with a mean age of 64.5 +/- 1.1 yr. A regression analysis was performed to determine the variables that correlated with intraoperative decrease in temperature and postoperative rewarming rate. The major correlates of greater intraoperative decrease in temperature were 1) GA (P = 0.003); 2) cold ambient OR temperature (P = 0.07); and 3) advancing patient age (P = 0.03). There was significant interaction between ambient OR temperature and type of anesthesia (P = 0.03): there was a greater intraoperative decrease in temperature with GA compared to EA in a cold OR but a similar decrease with GA and EA in a warm OR. The data also suggest an interaction between type of anesthesia and patient age (P = 0.06), showing a greater decrease in temperature with GA compared to EA in the younger patients, but a similar decrease between GA and EA in older patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642344 TI - Transcutaneous cardiac pacing in patients with automatic implantable cardioverter defibrillators and epicardial patch electrodes. AB - In patients with automatic implantable cardioverter defibrillators, insulation of the epicardial patch electrodes (patches) prevents externally applied current from passing through the electrode to the cardiac muscle so that external transthoracic and even internal defibrillation can be unsuccessful. Because emergency cardiac pacing may be required in such a case, a study was performed to evaluate whether, and at what threshold and electrode orientation, transcutaneous pacing is possible in patients with implanted patches. Thresholds for transcutaneous pacing were determined during general anesthesia in nine patients with patches sewn across the heart (anterior right and posterior left ventricles) either before or after surgery, or at both times (automatic implantable cardioverter defibrillator implantation/exchange with or without coronary artery bypass grafting). Because surgery per se can increase the pacing threshold, nine patients of similar body size and weight undergoing routine coronary artery bypass grafting also were evaluated and served as a control group. Pacing thresholds (stimulus duration: 50 ms) were determined during normothermia with a transportable transcutaneous pacer, and adult cutaneous electrodes were placed across the patients' chest in the standard anteroposterior and right-to-left orientations. In all patients with patch electrodes, antero-posterior pacing was possible at a mean threshold of 73 +/- 30 mA standard deviation (range: 40-140 mA). This threshold was not significantly different (Mann-Whitney test) from that in control patients before (57 +/- 20 mA; range: 30-90 mA) or after (94 +/- 24 mA; range: 40-120 mA) coronary artery-bypass grafting. The surgical procedure per se significantly increased the threshold (Wilcoxon test, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642345 TI - Intraarticular morphine, bupivacaine, and morphine/bupivacaine for pain control after knee videoarthroscopy. AB - Evidence has accumulated that opioids can produce potent antinociceptive effects by interacting with opioid receptors in peripheral tissues. This study sought to compare the effects of morphine with those of bupivacaine administered intraarticularly upon pain following arthroscopic knee surgery. In a double blind, randomized manner, 33 patients received either morphine (1 mg in 20 ml NaCl; n = 11), bupivacaine (20 ml, 0.25%; n = 11), or a combination of the two (n = 11) intraarticularly at the completion of surgery. After 1, 2, 3, and 4 h and at the end of the 1st and 2nd postoperative days, pain was assessed by a visual analogue scale, and supplemental analgesic requirements were recorded. Pain scores were significantly greater in the morphine group than in the other two groups at 1 h. There were no significant differences at 2 and 3 h. From 4 h until the end of the study period, pain scores were significantly greater in the bupivacaine group than in the other two groups. Analgesic requirements were significantly greater in the morphine group than in the other groups at 1 h but were significantly greater in the bupivacaine group than in the other groups throughout the remainder of the study period. We conclude that intraarticular morphine produces an analgesic effect of delayed onset but of remarkably long duration. The combination of these two drugs results in satisfactory analgesia throughout the entire observation period. PMID- 1642346 TI - Intrathecal clonidine as a sole analgesic for pain relief after cesarean section. AB - In a small number of studies and isolated case reports, intrathecally administered clonidine has been reported to relieve intractable cancer pain and to prolong spinal anesthesia induced by various local anesthetics. A double-blind placebo-controlled clinical trial was carried out in order to evaluate the effect of intrathecal clonidine on pain following cesarean section. Twenty patients who underwent elective cesarean section received, 45 min after general anesthesia, either 150 micrograms (n = 10) clonidine or saline (control group, n = 10) intrathecally. Pain scores were lower in clonidine- than saline-treated patients from 20 to 120 min after intrathecal injection, as measured by a visual pain linear analog scale (P less than 0.05). Pain relief, in terms of the first supplemental analgesic request by patients, lasted 414 +/- 128 min after intrathecal clonidine and 181 +/- 169 min (mean +/- SD) (P less than 0.01) after saline. Clonidine decreased systolic, diastolic, and mean arterial pressures compared to baseline values (P less than 0.05), but heart rate and central venous pressure were unaffected (difference not significant). Maximal reduction of systolic arterial pressure was 15 +/- 9%, of diastolic arterial pressure 22 +/- 12%, and of mean arterial pressure 18 +/- 12%. Clonidine did not affect arterial hemoglobin oxygen saturation or PaCO2. Patients in the clonidine group were significantly more sedated (P less than 0.05) and more frequently reported a dry mouth (P less than 0.01) compared to the normal saline group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642347 TI - Postoperative pain management by intranasal demand-adapted fentanyl titration. AB - The aim of the present study was to investigate whether intranasal administration of fentanyl allows a demand-adapted postoperative opioid titration. Forty-two patients who had undergone surgery for lumbar intervertebral disk protrusion were included in a prospective randomized double-blind study. When complaining about intense pain, 22 patients received six sprays of fentanyl (0.027 mg) intranasally and 6 ml sodium chloride 0.9% intravenously and 20 patients received six sprays of sodium chloride 0.9% intranasally and 6 ml of a diluted fentanyl solution (0.027 mg) intravenously. In both groups, these doses were repeated every 5 min until the patients were free of pain or refused further analgesic. Before the beginning of opioid titration and then every 10 min for at least 1 h, pain was evaluated with the aid of a 101-point numerical rating scale and a verbal rating scale. Blood pressure, heart rate, arterial hemoglobin oxygen saturation, respiratory rate, and side effects were recorded. All patients were satisfied with the pain reduction achieved. The total fentanyl dose was 0.073 mg (range 0.027-0.162) in the intravenous group and 0.11 mg (range 0.027-0.243) in the intranasal group. The onset of action after intranasal application was nearly as fast as after intravenous titration. The pain reduction achieved was comparable in both groups. Only at the (10-), 20- and 30-min measurement points was the pain intensity significantly lower in the intravenous than in the intranasal group. One patient of the intravenous group showed a decrease in arterial hemoglobin oxygen saturation to less than 90%. Other serious side effects were not observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642348 TI - Painful stimulation minimally increases the thermoregulatory threshold for vasoconstriction during enflurane anesthesia in humans. AB - Generalized autonomic stimulation enhances hemodynamic responses and may, in a similar fashion, facilitate thermoregulatory responses. We thus tested the hypothesis that painful stimulation increases the central temperature threshold for vasoconstriction during general anesthesia. Healthy volunteers were anesthetized with 1.3% end-tidal enflurane on 2 separate days. On 1 day (randomly assigned), painful stimulation was produced by tetanic electrical stimulation. On the other day, electrical stimulation was not given. Significant thermoregulatory vasoconstriction was defined as a forearm-fingertip skin-surface temperature gradient exceeding 4 degrees C. The distal esophageal temperature triggering significant vasoconstriction was considered the thermoregulatory threshold. The threshold was 35.5 +/- 0.8 degrees C during electrical stimulation and 35.1 +/- 0.6 degrees C without stimulation (P = 0.050, 95% confidence interval for the difference = 0-0.7 degree C). These data suggest that thresholds determined in nonsurgical volunteers will be slightly (but not clinically significantly) less than those in operative patients. Similarly, intraoperative vasoconstriction thresholds likely will be slightly less when surgical pain is prevented by simultaneous regional or local analgesia. PMID- 1642349 TI - Successful transplantation after long-term preservation of dog hearts. AB - Nucleoside transport inhibition is a new approach to long-term preservation of donor hearts. To evaluate its effectiveness, the following were tested: 1) the effect of nucleoside transport inhibition on high-energy phosphate content after cardioplegic arrest and during long-term cold storage (group I: cardioplegia, control ]n = 18]; group II: cardioplegia plus nucleoside transport inhibitor [n = 18]); 2) the effect of nucleoside transport inhibition on high-energy phosphates and hemodynamic recovery in a modified blood-perfused Langendorff system (group III: 24-h cold storage followed by reperfusion [n = 6]; group IV: addition of nucleoside transport inhibition to cardioplegia but not during reperfusion [n = 6]; group V: addition of nucleoside transport inhibition during reperfusion [n = 6]; group VI: addition of nucleoside transport inhibition to cardioplegia and during reperfusion [n = 6]); and 3) the effect of nucleoside transport inhibition added to cardioplegia and during reperfusion on high-energy phosphate content and outcome after heart transplantation (group VII: no nucleoside transport inhibitor in cardioplegia and during reperfusion [n = 8]; group VIII: addition of nucleoside transport inhibition to cardioplegia and during reperfusion [n = 8]). The following results were obtained: 1) addition of nucleoside transport inhibition prevented high-energy phosphate depletion during cold storage: after 24 h, adenosine triphosphate content in group I was 9.4 +/- 3.1 mumol/g versus 17.7 +/- 3.6 mumol/g dry weight in group II (P less than 0.05); 2) addition of nucleoside transport inhibition to cardioplegia and during reperfusion resulted in greater high-energy phosphate content (adenosine triphosphate in group III was 7.9 +/- 3.5 mumol/g vs. 17.8 +/- 2.8 mumol/g in group VI [P less than 0.05]) and improved hemodynamics upon reperfusion (hearts in group III did not recover, maximum isometric left ventricular pressure development was 1,635 +/- 577 mmHg/sec in group IV, 1,915 +/- 423 mmHg/sec in group V, and 2,437 +/- 201 mmHg/sec in group VI [P less than 0.05, group VI vs. groups IV and V]); and 3) hearts treated with nucleoside transport inhibition in cardioplegia and during reperfusion (group VIII) could be transplanted successfully in contrast to group VII hearts. These data indicate that nucleoside transport inhibition in dogs is highly effective in long-term preservation of donor hearts. PMID- 1642350 TI - Insufflated halothane increases venous admixture less than nitroprusside in canine atelectasis. AB - Although it generally is agreed that halothane is a pulmonary vasodilator, its effect on venous admixture and hypoxic pulmonary vasoconstriction are more controversial. The effects of 2.4% halothane on pulmonary vascular resistance and venous admixture were investigated in an isolated canine lobe made atelectatic. Halothane was administered by three different methods: insufflation, addition to the pulmonary artery blood through a bubble deoxygenator, or a combination of both techniques. Pulmonary vascular resistance was divided into arterial, venous, and middle segmental resistance by a vascular occlusion technique. Middle resistance increased with 3% O2 ventilation (0.0238 +/- 0.0092 cmH2O.ml-1.min-1) or after production of atelectasis (0.0225 +/- 0.0074 cmH2O.ml-1.min-1), compared to control ventilation in the nonatelectatic lung 0.01 +/- 0.0067 cmH2O.ml-1.min 1). Halothane by any delivery method variably decreased middle resistance, with increasing potency from addition of halothane through the bubble deoxygenator (0.0118 +/- 0.0047 cmH2O.ml-1.min-1) to halothane insufflation (0.0072 +/- 0.0058 cmH2O.ml-1.min-1), and finally to a combination of both techniques (0.0026 +/- 0.0041 cmH2O.ml-1.min-1). In contrast to vascular resistance, venous admixture in the atelectatic (8 +/- 5%) and nonatelectatic lobes (7 +/- 4%) was increased with halothane insufflation (11 +/- 4%), addition of halothane through the bubble deoxygenator (26 +/- 16%), and a combination of both techniques (22 +/- 13%). Compared to intravenous nitroprusside (26 +/- 12%), halothane insufflation was less potent in increasing venous admixture when total pulmonary vascular resistances were of similar magnitude (0.0526 +/- 0.0112 and 0.0484 +/- 0.0088 cmH2O.ml-1.min-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642351 TI - The effect of amrinone on recovery from severe bupivacaine intoxication in pigs. AB - Cardiovascular collapse following intravascular bupivacaine may be resistant to treatment. The effect of amrinone on recovery from bupivacaine-induced severe cardiovascular depression was evaluated in 20 pigs (13-26 kg) in a placebo controlled randomized double-blind study. Under 0.7% isoflurane anesthesia at FIO2 0.21, 0.5% bupivacaine 2 mg.kg-1.min-1 was infused until mean arterial pressure was 40% of the baseline. Cardiac output and heart rate decreased 75% and 50% from the baseline, respectively. The total dose of bupivacaine was 17 +/- 6 (SD) mg.kg-1 in the control and 19 +/- 5 mg.kg-1 in the amrinone group, resulting in mean plasma concentrations of 42 +/- 6 and 53 +/- 19 micrograms.ml-1, respectively. A bolus of amrinone 4 mg.kg-1 (n = 10) was given immediately after cardiovascular depression, followed by an infusion of 0.6 mg.kg-1.min-1. The control animals received corresponding volumes of physiologic saline (n = 10). After cardiovascular depression, the lungs were ventilated with FIO2 1.0 without anaesthetics or sympathomimetic support. Electric activity of the heart ceased in all control animals in 3.9 +/- 2 min after cardiovascular depression despite atropine and external cardiac compression. All animals in the control group and 5 of 10 animals in the amrinone group were given atropine (P less than 0.01). The animals receiving amrinone survived without cardiac compression (P less than 0.0001). During bupivacaine infusion, all animals developed burst suppression in the electroencephalogram. At the time of cardiovascular depression, in 8 of 10 control and in 6 of 10 amrinone animals, the electroencephalogram was isoelectric.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642352 TI - Mechanism underlying the changes in plasma potassium concentration during infusion of isosmotic nonelectrolyte solution. AB - Generally, during infusion of an isosmotic nonelectrolyte solution that permeates the cell membrane, plasma K+ concentration ([K+]pl) either does not change or it increases slightly. The mechanism underlying this [K+]pl change has not been clarified. We continuously monitored the [K+]pl and plasma Na+ concentration ([Na+]pl) for 10 min during isosmotic mannitol infusion of 1.6 ml/100 g body weight in rats with intact kidney function (intact mannitol group). In addition, in nephrectomized rats, we compared the [K+]pl change during infusion with isosmotic mannitol (which permeates the cell membrane; mannitol nephrectomized group) with that during infusion with isosmotic sucrose (which does not permeate the cell membrane; sucrose nephrectomized group) to evaluate the effect of cell volume regulation. In the intact mannitol group, [Na+]pl decreased with dilution, and [K+]pl remained relatively constant. In the sucrose nephrectomized group, [K+]pl decreased by the same percentage as [Na+]pl and gradually increased to greater than the control level. In the mannitol nephrectomized group, however, [K+]pl increased immediately after the beginning of the infusion and reached the same level as that in the sucrose nephrectomized group. To confirm that the difference in [K+]pl between the mannitol and sucrose nephrectomized groups was dependent on cell volume regulation, we investigated the changes in mean corpuscular volume of red blood cells, using a Coulter counter. This value remained constant during isosmotic sucrose infusion but increased during isosmotic mannitol infusion, returning to the original volume after the infusion. We kept [HCO3-] and pH constant throughout the experiments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642353 TI - Brain blood flow and metabolism do not decrease at stable brain temperature during cardiopulmonary bypass in rabbits. AB - Cerebral blood flow (CBF) during human hypothermic cardiopulmonary bypass has been reported to decrease with time, suggesting that progressive cerebral vasoconstriction or embolic obstruction may occur. We tested the hypotheses: 1) that observed CBF reductions were due to continued undetected brain cooling and 2) that CBF during cardiopulmonary bypass would be stable after achievement of constant brain temperature. Anesthetized New Zealand White rabbits underwent cardiopulmonary bypass (membrane oxygenator, centrifugal pump, bifemoral arterial perfusion) and were assigned to one of three bypass management groups based on perfusate temperature and PaCO2 management: group 1 (37 degrees C, n = 8); group 2 (27 degrees C, pH-stat, n = 9); and group 3 (27 degrees C, alpha-stat, n = 8). Systemic hemodynamics, and cerebral cortical, esophageal, and arterial perfusate temperatures were recorded every 10 min for the first hour of bypass and again at 90 min. CBF and masseter blood flow (radiolabeled microspheres) were determined at 30, 60, and 90 min of bypass, while the cerebral metabolic rate for oxygen (CMRO2) was determined at 60 and 90 min. Groups were comparable with respect to mean arterial pressure, central venous pressure, hematocrit, and arterial oxygen content throughout bypass. Cortical temperature was stable in normothermic (group 1) animals, and there was no significant change in CBF between 30 and 90 min of bypass: 68 +/- 18 versus 73 +/- 20 ml.100 g-1.min-1 (mean +/- SD). In the hypothermic groups (2 and 3), cortical temperature equilibration (95% of the total change) required 41 +/- 6 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642354 TI - Treatment of proximal aortic hypertension after thoracic aortic cross-clamping in dogs. Phlebotomy versus sodium nitroprusside/isoflurane. AB - Thoracic aortic cross-clamping causes proximal aortic hypertension. Theoretically, the method used to treat hypertension can influence spinal cord perfusion pressure and neurologic outcome. Phlebotomy was compared to sodium nitroprusside/isoflurane in terms of ability to treat increased proximal mean aortic pressure (MAPp) after thoracic aortic cross-clamping in dogs. Dogs were assigned randomly to one of three groups depending on the method used to treat hypertension after cross clamping: 1) phlebotomy (n = 10); 2) sodium nitroprusside/isoflurane (n = 11); and 3) control (no treatment) (n = 8). In each dog, anesthesia was maintained with isoflurane in oxygen, 1.4% end-tidal. The thoracic aorta was occluded 2.5 cm distal to the left subclavian artery for 50 min and then was released. Hemodynamics, cerebrospinal fluid pressure (CSFP), and regional blood flows by the radioactive microsphere technique, were measured at 1) baseline; 2) 2 min after aortic cross-clamping; 3) after treatment of proximal aortic hypertension; 4) 5 min after aortic unclamping; and 5) 30 min after resuscitation. At 24 h, a neurologic assessment was performed. Thoracic aortic cross-clamping increased MAPp, decreased distal MAP (MAPd), and reduced lumbar spinal cord perfusion pressure (SCPPl), [SCPPl = MAPd - CSFP], in all three groups. Control of increased MAPp necessitated removal of 36 +/- 9 ml/kg of blood in the phlebotomy group. In the sodium nitroprusside/isoflurane group, sodium nitroprusside (16 micrograms.kg-1.min-1) was infused and end-tidal isoflurane concentration increased to 2.5 +/- 0.7%, restoring MAPp to baseline level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642355 TI - Selective effects of pentobarbital and halothane on c-fos and jun-B gene expression in rat brain. AB - The effects of pentobarbital and halothane anesthesia on the expression in brain of the immediate-early genes c-fos and jun-B were investigated. Pentobarbital anesthetized rats (n = 10) received a single intraperitoneal injection of pentobarbital 65 mg/kg in a vehicle of 40% propylene glycol and 10% ethanol and then were placed in a plexiglass box flushed continously with 100% oxygen at 5 l/min. Halothane-anesthetized rats (n = 10) received an intraperitoneal injection of vehicle only and were transferred to a box flushed continuously with oxygen plus 1.5% halothane. Unanesthetized control rats (n = 10) received an intraperitoneal injection of vehicle and were placed in a box flushed continuously with 100% oxygen. Four additional rats received no intraperitoneal injection but were handled and otherwise treated identically to the control group, and six others had a femoral arterial catheter inserted for blood pressure and blood gas measurements. Five animals from the control and both anesthetized groups were killed at 30 and 120 min postinjection and their brains rapidly removed and frozen. The messenger ribonucleic acid transcription products of the genes c-fos, jun-B, and beta-actin from whole cerebral hemispheres were analyzed autoradiographically after Northern blot hybridization with 32P-labeled deoxyribonucleic acid probes. Relative levels of c-fos and jun-B messenger ribonucleic acid were determined from optical density measurements of the autoradiographic bands, with beta-actin measurements being used to correct for sample-to-sample variation. Rats became immobile within minutes of drug administration and remained anesthetized until they were killed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642356 TI - Latex anaphylaxis in a child with a history of multiple anesthetic drug allergies. PMID- 1642357 TI - Anesthetic management of patients undergoing cardiomyoplasty. PMID- 1642358 TI - The institution of veno-venobypass by peripheral cannulation under emergent intraoperative conditions. PMID- 1642359 TI - Anaphylaxis due to propofol. PMID- 1642360 TI - Kartagener's syndrome: anesthetic considerations. PMID- 1642361 TI - Pulmonary artery hypertension complicating anesthesia for liver transplantation. PMID- 1642362 TI - Fewer failed spinal anesthetics with the Sprotte needle. PMID- 1642363 TI - Adverse outcomes and the multicenter study of general anesthesia: I. PMID- 1642364 TI - Adverse outcomes and the multicenter study of general anesthesia: II. PMID- 1642365 TI - A few details regarding tonometric measurement of blood pressure. PMID- 1642366 TI - When the endotracheal tube will not pass over the flexible fiberoptic bronchoscope. PMID- 1642367 TI - Machine wars: another cause of pressure loss in the anesthesia machine. PMID- 1642368 TI - Design flaw in an anesthesia machine. PMID- 1642369 TI - A simple alternate technique for the application of the pulse oximeter probe to infants. PMID- 1642370 TI - Intubation and extubation of the patient with Pierre-Robin syndrome. PMID- 1642371 TI - Position of the laryngeal mask airway. PMID- 1642372 TI - Intracranial elastance versus intracranial compliance: terminology should agree with that of other disciplines. PMID- 1642373 TI - Data management and accountability in behavioral and biomedical research. AB - Regulations recently enacted by the Public Health Service and the National Science Foundation to address misconduct in scientific research were designed primarily to curtail deliberate forms of misconduct, such as fabrication or falsification of findings; however, researchers may also be held accountable for inadvertent deficiencies in data management. This article examines some of the problems in data quality control, documentation, and data retention that can occur when computers are used in scientific research. It focuses on deficiencies that could make it difficult to verify the integrity of research data or to reproduce statistical analyses. Strategies for prevention of data management problems are recommended. PMID- 1642374 TI - Why the gap? Practice and policy in civil commitment hearings. AB - The failure of civil commitment procedures to meet statutory requirements is one of the more reliable findings in the applied social sciences. Most states now require specific legal procedures and behavioral standards for involuntary hospitalization. Nonetheless, empirical studies have demonstrated that commitment hearings are rarely adversarial and clinical concerns continue to take precedence over legal issues. These findings are analyzed in the context of three related issues: the grounds for commitment that are used in civil commitment hearings, the particular difficulties of recommitment hearings, and the shortcomings of the national policy of deinstitutionalization. The authors conclude that a primary cause of the gap between legal standards and actual practice is the absence of viable, less restrictive alternatives to inpatient treatment. PMID- 1642375 TI - Where's poppa? The relative lack of attention to the role of fathers in child and adolescent psychopathology. AB - Compared with mothers, fathers are dramatically underrepresented in clinical child and adolescent research. The author reviewed empirical and theoretical clinical child and adolescent literature to ascertain the reasons for this underrepresentation. Four somewhat interrelated factors are discussed: practical issues in participant recruitment, differential base rates of paternal vs. maternal psychopathology, theory-driven research based on sexist theories, and research assumptions based on outdated societal norms. Suggestions for future research are discussed, including parallel investigations of paternal characteristics whenever maternal characteristics are investigated, assessment of both similarities and differences in the role of fathers and mothers in child and adolescent psychopathology, and investigation of parenting factors for both fathers and mothers (e.g., time spent in actual caretaking, career vs. family orientation) in relation to child and adolescent psychopathology. PMID- 1642376 TI - Prospective evaluation of a double-lumen subclavian dialysis catheter for acute vascular access. AB - The safety and efficacy of a parallel, double-lumen hemodialysis catheter used to achieve acute, temporary vascular access were evaluated prospectively in 134 hospitalized adult patients in whom 162 catheters were placed. The arterial flow rates and venous resistance were such that 84 per cent of the catheters provided satisfactory access for dialysis. Minor manipulations of the catheter were frequently required to maximize function. Three serious complications occurred, including one instance each of pneumothorax, hemorrhage, and nonfatal pericardial tamponade. PMID- 1642377 TI - Carotid arterial surgery using local anesthesia: a private practice retrospective study. AB - Carotid endarterectomy has recently become one of the more controversial operations. The tremendous increase in the number of endarterectomies performed, coupled with the apparent increase in morbidity and mortality associated with this operation in some studies, have brought into question the indications and results of the procedure. The potential for complications from the procedure itself, as well as increased morbidity and mortality from surgery on the elderly, make carotid endarterectomy a dangerous operation that must be done carefully and thoughtfully. The authors have performed carotid endarterectomies exclusively under local anesthesia to more closely evaluate the neurologic status of the patient. They believe that the operation performed in this manner obviates the use of a shunt and its inherent complications in greater than 80 per cent of the patients. This, coupled with the fact that many of the patients also have severe cardiac disease and the use of local anesthesia causes less hemodynamic changes and stress, should make carotid endarterectomy under local anesthesia the preferred approach. PMID- 1642378 TI - Post-traumatic pseudoaneurysm of the left hepatic artery initially appearing as upper gastrointestinal hemorrhage secondary to hepatic artery-duodenal fistula. A case study. AB - Post-traumatic hepatic artery pseudoaneurysm initially appearing as upper gastrointestinal hemorrhage secondary to rupture in the duodenum is rare. Diagnosis was made on selective arteriogram and the patient was managed successfully by ligating the feeding vessel to the aneurysm. PMID- 1642379 TI - An unusual case of intermittent venous obstruction of the upper extremity. AB - The axillary vein can be subject to intermittent obstruction from numerous anatomic structures such as the pectoralis minor and the scalenus anterior muscles. The diagnosis can be readily made on history and physical examination of the upper extremity, but it can be difficult to confirm by routine venogram done with the arm in the standard position at the side with full extension at the antecubital fossa. Positional venography with the arm fully abducted and flexion of that antecubital fossa allows for better definition of this extrinsic compression. In the case presented, a fascial band arising from the medial head of the biceps was compressing the axillary vein and was suspected on history and physical examination; it was confirmed with positional venography as noted. As in this case, it is important to make the diagnosis early, before thrombosis of the vein occurs, to minimize the associated morbidity. Transaxillary exploration was performed with excision of the band and complete resolution of the symptoms. Subsequent noninvasive studies were performed that showed complete resolution of the extrinsic axillary vein compression. Having a high suspicion of intermittent venous obstruction with early diagnosis and surgical correction of any extrinsic compression are the keys to a successful outcome in these patients. PMID- 1642380 TI - A new, compound-curved needle for vascular surgery. AB - A new, compound-curved needle has been designed and developed for vascular surgery from a unique stainless steel alloy, American Society for Testing Materials (ASTM) 45500. This needle has two different radii of curvature and a relatively straight body followed by a short, curved tapered point. Despite its geometry, it exhibits a similar sharpness, as well as resistance to bending and breakage, as did a curved needle with a single radius of curvature manufactured from the same alloy. The design of this new needle enabled the surgeon to pass it through the vessel wall with greater accuracy to a controlled depth and length of bite than the curved cutting edge needle with a single radius of curvature. PMID- 1642381 TI - The influence of vascular certification on lower extremity revascularization at one institution. AB - The potential impact of vascular certification on the practice of vascular surgery at Maricopa Medical Center (Phoenix, AZ) was analyzed by comparison of lower extremity revascularization results over consecutive 2-year periods before (Period I) and after (Period II) institution of vascular surgery service. The overall setting (county hospital, surgical residency) and ancillary services (Anesthesia, Intensive Care Unit, Radiology) were unchanged, except for the authors' use of invasive hemodynamic support. In Period I, there were 49 cases (30 inflow, 19 outflow) with 14 per cent (7/49) mortality, 32 per cent (21/67) limb thrombosis or embolus, and 10 per cent (5/49) graft infection; 80 per cent (39/49) of operations were done for claudication; 20 per cent (10/49) were done for inappropriate indications (P less than 0.005). In Period II, there were 110 cases (47 inflow, 63 outflow). The increase in cases was predominantly due to increased use of extra-anatomic inflow and complex infrapopliteal outflow reconstructions. Seventy per cent (77/110) of operations were done for limb salvage; of 17 aortic cases, 3 were "re-do's" and 5 underwent simultaneous renal revascularization. There was a 3 per cent (4/110) mortality (P less than 0.025), 11 per cent (13/137) limb thrombosis or embolus (P less than 0.005), and no graft infections (P less than 0.001). Lower extremity revascularization delivered by certified vascular surgeons was offered to more patients with lower overall mortality and morbidity rates after more thorough diagnostic work-up and for more appropriate indications, with concomitant use of more refined vascular techniques/procedures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642382 TI - The use of epidural anesthesia and analgesia in aortic surgery. AB - During a 3-year period, sixty-four consecutive patients, who had elective aortic reconstruction were investigated to determine whether epidural anesthesia and analgesia, combined with light general anesthesia, would lower the rate of perioperative complications in this high-risk group of patients. The epidural group comprised 32 consecutive patients who had surgery during the 20-month period from July 1986 to December 1987. These patients were compared with the previous 32 patients who had aortic reconstruction at Huntington Memorial Hospital (Pasadena, CA) using conventional general anesthetic techniques. Cardiovascular and respiratory morbidity, length of hospital stay, length of intensive care unit stay, and duration of endotracheal intubation were compared. There was no statistically significant difference in cardiovascular morbidity, length of hospital stay, or intensive care unit stay between the two groups. There was however, a striking decrease in respiratory complications and length of intubation in the epidural anesthesia group (P less than 0.005). The authors conclude that epidural anesthesia and analgesia, combined with a light general anesthetic may confer benefits over conventional general anesthesia in patients undergoing aortic surgery. PMID- 1642383 TI - Changing patterns in the predisposition for amputation of the lower extremities. AB - The purpose of this study was to evaluate and determine the role of diabetes and other common predisposing factors in amputation of the lower extremities. A retrospective review of 110 patients with peripheral vascular disease who underwent amputation between 1987 and 1990 at Hahnemann University Hospital (Philadelphia, PA) was performed. Patients who underwent amputations for trauma or cancer were excluded from this analysis. The patients were divided into four groups according to the site of amputation: Above Knee (n = 43), Below Knee (n = 26), Foot (n = 7) and Transmetatarsal (n = 34). The mean age was 60 years. Fifty five patients (51%) were white. Sixty-four patients (58%) were men. Twenty-nine patients (26%) were cigarette smokers; sixteen smokers (55%) had above-knee amputation. Thirty-five patients (32%) had previous vascular surgery of the lower extremities. The combination of diabetes and hypertension was present in 40 patients (36%). When either diabetes or hypertension alone was present in a patient, hypertension, not diabetes, was more commonly the dominant underlying medical condition in patients with amputation (32 hypertension-alone patients vs. 10 diabetes-alone patients). The high frequency of hypertension suggests that enhanced control of this disease may affect peripheral vascular disease and related amputations in the future. PMID- 1642384 TI - Risk factors for myocardial infarction after distal arterial reconstructive procedures. AB - This study identifies the preoperative, intraoperative, and postoperative factors associated with perioperative myocardial infarction (MI). The records of all patients who had distal vascular reconstructive procedures who sustained a perioperative MI were retrospectively reviewed from 1977 to 1990. From a total of 767 procedures, 18 (2.3%) patients suffered a MI. The mean time to MI after surgery was 1.8 days. Diabetes, heart murmur, and previous major amputations were identified as significant risk factors for the development of a perioperative MI. No laboratory or cardiographic data correlated with an increased risk, and the Goldman Index was inadequate in predicting perioperative MI risk. PMID- 1642385 TI - Simple modification for a more secure vascular clamp. AB - Large, atraumatic vascular clamps can be prone to slippage, especially at the toe. A simple modification of the clamp is described along with an illustration. PMID- 1642386 TI - Prevalence of ischemic nephropathy in patients with renal insufficiency. AB - To estimate its clinically unsuspected prevalence among patients with renal insufficiency, renal duplex sonography (RDS) was used to estimate the presence of critical renal artery stenosis (RAS) in that population. Patients, aged 45 to 75 years, with a serum creatinine of greater than or equal to 2.0 mg% but without dialysis dependence, prior renal transplantation, or prior renal artery surgery were considered for RDS. Fifty-three patients who met criteria for study were randomly selected from the Section of Nephrology clinic files and each patient was contacted both by mail and by telephone. Twenty-five patients agreed to RDS, and renal artery anatomy was determined in 21 patients using standardized RDS techniques. These techniques have demonstrated an overall accuracy of 96 and 97 per cent when compared prospectively to conventional angiography during validity analyses in the authors' center. Results of RDS revealed significant findings in 5 of 21 patients (24%). Three patients demonstrated criteria for ischemic nephropathy (IN): one patient had RAS with contralateral renal artery occlusion confirmed by angiography, while 2 patients demonstrated unilateral RAS. An abdominal aortic aneurysm and unilateral hydronephrosis were discovered in the fourth and fifth patients. Evaluation of patient demographic data and functional parameters as predictors of IN revealed that the duration of renal insufficiency at the time of RDS and extra-renal organ-specific atherosclerotic damage were significantly different between the groups with and without IN. The authors preliminary findings suggest that unsuspected ischemic nephropathy may exist in a significant minority of patients with renal insufficiency. PMID- 1642387 TI - Preoperative spirometry predicts perioperative pulmonary complications after major vascular surgery. AB - This study determined utility of preoperative spirometry for prediction of postoperative pulmonary complications (PPC) defined as pneumonia, ventilator dependence greater than 48 hours, and adult respiratory distress syndrome in 147 patients undergoing vascular surgery from June 1988 through March 1990 [39 aortic aneurysm repairs, 21 carotid procedures, and 87 operations for occlusive disease including aorto-ileofemoral, infra-inguinal, and visceral]. The incidence of PPC was 12.9 per cent, while cardiac complications (myocardial infarction, congestive heart failure, and ventricular arrhythmias) were present in 9.8 per cent. Prior or current smoking, which was present in 80 per cent, was not predictive of PPC. FEV1 was 2.2 +/- 0.7 L/s (mean +/- 1 SD). Abnormal FEV1 (2.0 or less L/s) was present in 42 per cent (n = 62). For FEV1 of 2.0 or less, PPC rate was 22.5 per cent versus 5.8 per cent for FEV1 greater than 2.0 L/s (P less than 0.005, Fisher exact). The incidence of PPC was 30.7 per cent for aortic aneurysm repair, 8.0 per cent for occlusive disease, and 4.7 per cent for carotid procedures. Abdominal aortic procedures (performed in 67 patients: 39 for aortic aneurysm repair and 28 for aortoiliac occlusive disease) were associated with a PPC rate of 22.4 per cent versus 5.0 per cent for "nonabdominal" procedures (P less than 0.002, Fisher exact). Life table analysis after surgery demonstrated decreased survival for patients with PPC (P = 0.031, Mantel-Haensel) during follow-up (250 +/- 165 days). PPC are associated with abnormal FEV1 and abdominal vascular procedures. In conclusion, preoperative spirometry is useful for the prediction of PPC after vascular surgery. PMID- 1642388 TI - The ruptured abdominal aortic aneurysm in a community hospital. A 5-year study. AB - The authors report on a recent 5-year experience with the treatment of ruptured abdominal aortic aneurysms in a community hospital located in a frequently visited tourist center. Their mortality rate of 43 per cent compares favorably with accepted mortality rates from large teaching institutions. Several known complications of this condition occurred in the authors' series. The most ominous complications that carried the highest associated mortality rates, if the patient did not succumb in the operating room, were acute tubular necrosis (75% associated mortality) and bowel infarction (100% associated mortality). Most important, physicians must have a high index of suspicion to make the diagnosis early. As reported in other series, prolonged hypotension and blood loss has a direct correlation with high mortality. PMID- 1642389 TI - A note on the historical aspects of dysphagia lusoria. AB - There is a lack of appreciation for the fact that, in less than 1 per cent of the general population, the right subclavian artery has an anomalous origin and course. Fortunately, most of these persons do not have symptoms; however, if they should have neck surgery, they may be at increased risk for damage to the right inferior laryngram nerve. The earliest reported description of an anomalous right subclavian artery was that of Hunald in 1735; 52 years passed before the clinical syndrome of dysphagia lusoria was published by Bayford in 1787. Bayford did not mention the associated displacement of the right inferior laryngeal nerve. In 1823, Stedman described the entire anatomical picture. PMID- 1642390 TI - Splenic artery stump back pressure. AB - Splenic arterial collateral hemodynamics were measured during splenic artery occlusion in 15 patients who had splenic to left renal artery bypass. The mean splenic artery stump back pressure during proximal splenic artery clamping was 48.0 +/- 9.8 mmHg (mean +/- ISD) and the mean collateral splenic perfusion pressure was 34.3 +/- 9.4 mmHg. The lowest measured back pressure was 39 mmHg and the lowest perfusion pressure was 30 mmHg. There were no spleen complications after operation. These measurements establish a normal range for collateral splenic perfusion pressure. These results may be helpful in clinical decisions about the adequacy of splenic circulation in operations that require division of the splenic artery or the short gastric arteries when there is celiac axis or splenic artery occlusive disease. PMID- 1642391 TI - Clinical experience with polytetrafluoroethylene (PTFE) in the aortobifemoral position. AB - Between 1981 and 1990, 18 patients (mean age 66.0 years) had aortobifemoral bypass with polytetrafluoroethylene (PTFE) bifurcated grafts. Twelve patients (66.7%) were treated for aortoiliac occlusive disease, 5 patients (27.8%) for abdominal aortic aneurysms and one patient (5.6%) had surgery for hypoplastic aortic syndrome. The authors' overall complication rate was 16.7 per cent and included formation of an anastomotic pseudoaneurysm (1/18, 5.6%), graft infection (1/18, 5.6%), and graft thrombosis (1/18, 5.6%). Sixteen patients were followed for a mean period of 41.4 months. In this subgroup of patients the patency rate was 93.8 per cent. The authors conclude that the PTFE bifurcated graft is a suitable conduit for use in aortobifemoral bypass surgery. PMID- 1642392 TI - Hemicorporectomy for acute aortic occlusion: a case study. AB - Hemicorporectomy has been done for potentially curable pelvic malignancy and for intractable pelvic sepsis with bone involvement. In this report, the authors describe the first use of hemicorporectomy to treat ischemic gangrene of the limbs and pelvic soft tissues secondary to acute aortic occlusion. PMID- 1642393 TI - [Isolation of Leishmania major in Phlebotomus papatasi in Biskra (Algeria). The end of an ecoepidemiological saga]. AB - Out of 1,167 females of sandflies dissected, one specimen of Phlebotomus papatasi captured at a transmission site near Biskra, a well known Algerian focus of zoonotic cutaneous leishmaniasis, was found naturally infected with Leishmania major zymodeme MON-25. This supports classical observations of Sergent and al. P. papatasi as vector in this focus in 1921. PMID- 1642394 TI - The current management and prognosis of acral lentiginous melanoma. AB - A computer-aided retrospective analysis was performed on 359 patients with stage I and II melanoma at the time of diagnosis (disease confined to the primary melanoma), at the University of South Florida (Tampa, FL). Eighteen patients were identified with primary melanoma in acral locations, most being acral lentiginous melanoma. A comparison of actuarial survival curves of patients with melanoma in four different locations (acral, head and neck, trunk, and other extremity site) was performed. The patients with melanoma in acral locations did not have a statistically different actuarial survival than those with primary melanoma in other sites. When actuarial disease-free survival curves were constructed, however, acral primary melanoma had a shorter interval to recurrence than those located on the trunk or other extremity sites. Differences between actuarial disease-free survival for the head and neck and for acral primary sites were not significant. To identify prognostic factors responsible for the decreased disease free survival of the acral lentiginous population, a regression analysis was performed. Three prognostic factors were analyzed for stage I and II melanoma, including Breslow tumor thickness, ulceration of the primary lesion, and primary site location. In the univariate analysis, with each prognostic factor acting independently, tumor thickness (p less than 0.01) and ulceration (p = 0.02) were significant variables influencing the disease-free interval. Primary site did not, however, add prognostic information to the model (p = 0.54). A stepwise multivariate analysis confirmed this finding. PMID- 1642395 TI - Immunotherapy for malignant melanoma with a tumor cell vaccine. AB - Specific active immunotherapy for melanoma has been administered to several thousand patients since 1972, using an irradiated whole-cell preparation. A humoral response to vaccination can be demonstrated in a large percentage of patients. This response increases while immunizations are continued and decreases after cessation of therapy. The vaccinations are well tolerated; however, the therapeutic impact of this whole-cell vaccine awaits a randomized trial for definitive evaluation. PMID- 1642397 TI - The genetics of malignant melanomas. AB - A review of the hereditary aspects of the malignant melanomas showed causal heterogeneity and similar pathogenesis based on the dysregulation of the paracrine/autocrine growth mechanisms. The genetically different malignant melanomas have a range of recurrence risks from 1% for the nonfamilial, solitary, malignant melanoma to a risk exceeding 70% for the syndromic melanomas of neurocutaneous melanosis and the nine types of xeroderma pigmentosum. A recurrence risk of 6% is relevant to the members of dysplastic nevus syndrome families without malignant melanomas and the risk increases in excess of 50% for the individuals of families with dysplastic nevi and more than one malignant melanoma. PMID- 1642396 TI - Active specific adjuvant immunotherapy with vaccinia melanoma oncolysate. AB - Vaccinia melanoma oncolysate is an investigative agent for active specific adjuvant immunotherapy. Viral oncolysate work in animals has led to application of this treatment in humans. Success of initial trials in treatment of melanoma has led to a phase III randomized, prospective, double-blind, multi-institutional trial, which is currently under way. PMID- 1642398 TI - Prospects for cellular immunotherapy for metastatic melanoma. AB - Systemic therapy for metastatic malignant melanoma has been disappointing. The search for alternate therapeutic methods includes investigation of the interaction between melanoma and the human immune system. A cellular immune response to melanoma has been documented in vitro and in vivo. In most patients with disseminated disease, however, immune T cells fail to eradicate the tumor. While this phenomenon is poorly understood, the occasional occurrence of spontaneous regression provides some indication that the immune response may, in fact, be capable of eradicating established tumor in vivo. Current efforts to augment and to direct the immune response to melanoma include investigation of specific and nonspecific adoptive immunotherapy. Specific therapy includes the generation of tumor-activated specific killer cells from peripheral blood, draining nodes, or metastatic tumor deposits. An increasing understanding of antigen recognition and improved methodology for T-cell culture are contributing toward the application of cellular immunotherapy to patients with melanoma. PMID- 1642399 TI - Prospects for gene therapy and lymphokine therapy for metastatic melanoma. AB - Conventional treatment of cancer, especially for patients with metastatic melanoma tumor, is often ineffective. Immunotherapy and recently introduced gene therapy have revolutionized the treatments of patients with metastatic melanoma tumor. Use of biological response modifiers, such as interleukins and interferons, have been found to enhance therapeutic benefits to patients with malignant melanoma. Initial studies with a high-dose interleukin-2 (IL-2) therapy have proved effective in patients with melanoma tumor, although a variety of systemic toxicities were observed. A low-dose IL-2 continuous infusion has shown a similar response in patients with melanoma tumor, but produced lesser toxicity. The low-dose IL-2 therapy has been studied with an adoptive transfer combined with either autologous lymphokine activated killer cells or autologous tumor infiltrating lymphocytes (TIL). IL-2 in combination with chemotherapeutic agents such as flavone acetic acid, dacarbazine, and cyclophosphamide have also been studied in patients with metastatic melanoma. Results have shown a moderate response in patients with metastatic melanoma. TIL therapy, however, has been shown to result in higher objective regression due to potent tumor-specific killing and tumor-specific targeting characters of the TIL. The tumor targeting nature of the TIL creates the possibility of using TIL as a vehicle to deliver gene product specifically to tumor tissue. Safety and toxicity of gene-transduced TIL were addressed by the use of neomycin-resistant, gene-transduced TIL in patients with metastatic melanoma. We also investigated the use of vaccinia oncolysate therapy by using the viral oncolysate prepared with IL-2 gene encoded vaccinia virus. Preliminary studies with murine hepatic metastases colon model have shown encouraging results. PMID- 1642400 TI - Psychosocial aspects of melanoma. AB - Seventy-five patients with melanoma were surveyed for recent history of major stress, coping styles, and psychiatric disturbance. Recurrence of disease was strongly related to biological variables (stage and Breslow depths) but not to psychological measures. Major life stress was not related to stage, Breslow, Clark level, or estimates of lymphocytic infiltration of tumor. Coping styles were paradoxically related to major life stress such that history of major stresses was associated with greater confrontation of the melanoma diagnosis, greater will to fight the disease, and less avoidance of its frightening aspects. Experience with fewer major life stresses was associated with a defeatist attitude characterized by an expectation of a poor prognosis and little control over outcomes. More than 50% of the sample had experienced at least one major life stress in the past 5 years. This figure is consistent with prior work and indicative of a higher than normal rate of major life stress in the years before diagnosis. PMID- 1642401 TI - Treatment of the primary in malignant melanoma of the skin. AB - Surgical excisional therapy of malignant melanoma is the primary method of treatment for malignant melanoma. The exact size of the excisional therapy depends on the depth and location of the tumor. At the University of South Florida (Tampa, FL), tumors less than 0.76 mm in depth are resected with a 1-cm margin and tumors greater than 0.76 mm in depth are resected with a 3-cm margin. The location of the tumor also determines the exact margin of excision. Maximal reconstructive efforts following general principles of plastic and reconstructive surgery are noted and used for producing an optimal functional and aesthetic result. PMID- 1642402 TI - Etiology and prognosis of local recurrence in malignant melanoma of the skin. AB - All patients with stage I and stage II malignant melanoma of the skin were analyzed for stage; time of local, regional, or systemic recurrence, or two or more of these events; presence or absence of ulceration of the primary tumor; thickness of the primary tumor; level of invasion according to Clark; and margins of resection. Local recurrence had a significant negative impact on the long-term survival of patients. Our data revealed that local recurrence had the same poor prognostic effect as regional or systemic recurrence, or both. Factors significant in predicting local recurrence included the primary tumor characteristics of ulceration of the primary tumor and thickness of the primary tumor. Margins of resection and level of invasion were not noted significant in predicting local recurrence. PMID- 1642403 TI - Lymphoscintigraphy in malignant melanoma. AB - The development and rationale for the use of lymphoscintigraphy in the preoperative evaluation of patients with malignant melanoma being considered for elective lymph node dissection is reviewed. This overview is updated by an analysis of 135 patients with early stage malignant melanoma involving the head, neck, shoulders, and trunk at Moffitt Cancer Center and Research Institute at the University of South Florida (Tampa, FL). High discordancy rates (overall, 41%) were seen between drainage patterns predicted from historical anatomical guidelines and those revealed by the lymphoscintigraphic examination. The high discordancy rate was most pronounced in the head (64%) and the neck (73%). Surgical management was changed in 33% of the patients, overall. A preoperative lymphoscintigram is recommended for all patients with melanoma with head, neck, and truncal lesions evaluated for elective lymph node dissection as the lymphatic drainage patterns are often unpredictable and variable. PMID- 1642404 TI - The concept of lymph node dissections in patients with malignant melanoma. AB - Therapeutic lymph node dissections in patients with grossly palpable metastatic melanoma are performed to control regional disease, to salvage a small percentage of patients, and to obtain staging information. Patients with malignant melanoma may undergo elective lymph node dissections, when the basin is clinically negative, for three reasons. There is some evidence based on large retrospective studies that survival is increased in patients with intermediate thickness melanoma if elective lymph node dissections are performed as part of the initial treatment of the primary melanoma. Second, in a small percentage of patients, a previous elective lymph node dissection may have helped control disease in the regional lymphatics, so that more extensive procedures, including amputations, are not necessary. Another important reason is to obtain staging and prognostic information for the patient because most adjuvant protocols are based on the presence or absence of disease in the regional basin. During a 3-year period, 115 patients have undergone a regional nodal dissection at the Moffitt Cancer Center and James Haley VA Hospital as part of their surgical treatment. With a follow-up of 3 years, patients with 1 node positive do significantly better than those with more than 1 node positive in their dissection (p = 0.06). The percentage of nodes positive is also important. Those patients who have less than 10% of their nodes involved with metastatic melanoma have a better survival than those patients whose percentage is greater than 10% (p = 0.07). PMID- 1642405 TI - Recurrent malignant melanoma: the identification of prognostic factors to predict survival. AB - The prognostic factors for stage 1, 2 melanoma have been elucidated. Tumor thickness, ulceration of the primary melanoma, and perhaps, primary site may be used to predict the percentage of patients with regional nodal disease or systemic metastases and the prognosis of patients who have only cutaneous disease at diagnosis. Very little is known about prognosis once there is a recurrence. A retrospective, computer-aided chart review identified 4,185 patients registered at the Duke University Melanoma Database who had stage 1, 2 disease at diagnosis. During a mean follow-up period of 7 years, 35.9% experienced a recurrence. Local regional recurrences explained 62.5% to 85.5% of the recurrences. Even after elective node dissections, local regional recurrences explained most relapses (58.1%). Sixty-five percent of the recurrences occurred within the first 3 years of of follow-up. There was a pronounced difference in 5-year survival in those patients who suffered a recurrence sometime during their clinical course compared with those who never relapsed (p = 0.00001, for trunk primary melanoma). Patients with local or regional recurrence have a better prognosis than patients who relapse systemically, with 5-year survivals from the time of recurrence of 55% for a patient with a local recurrence, 51% for a patient with a regional nodal recurrence, and 20% for a patient with a systemic recurrence. A multivariate regression analysis identified thickness, ulceration of the primary melanoma, and age and location of the primary melanoma on the extremity as variables that predicted prognosis. The only factors concerning the recurrent state that added prognostic information was the disease-free interval and the presence of systemic metastases as the initial recurrence. PMID- 1642406 TI - Isolated limb perfusion for recurrent melanoma of the extremity. AB - Recent reports in the literature suggest that hyperthermic isolated limb perfusion (HILP) may be effective in preventing local recurrence in patients with deeply invasive melanoma or in patients with recurrent disease confined to the extremity. It has been used in the past as an adjuvant treatment after resection of the primary melanoma or recurrence, or as a therapeutic measure if all the disease on the extremity cannot be resected. A prospective, nonrandomized trial of 16 patients with melanoma with recurrent disease confined to the extremity underwent HILP. The protocol involved the wide local excision of all recurrent disease when possible, elective or therapeutic node dissection when indicated, and HILP using cisplatin. In 11 patients in whom all recurrent disease could be resected and the HILP was considered prophylactic, only 1 patient's disease has recurred in the perfusion circuit. Before the perfusion, the 11 patients had a total of 19 local or intransit recurrences. Of the 5 patients in whom all recurrent disease could not be resected, disease persisted in 4 patients. When compared with a concurrent control population of patients with extremity melanoma who had a local recurrence and were not perfused, the patients with melanoma who underwent HILP had a significant prolongation of disease-free survival (p less than 0.05), but a similar actuarial survival. In this study, we demonstrate that HILP can prevent local regional recurrences in patients with metastatic melanoma who are at high risk for further recurrence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642407 TI - The evaluation of putative tumor markers for malignant melanoma. AB - Biomarkers have long held out the promise that malignancies might be diagnosed early and that patients could be monitored more confidently during their clinical course to more reliably predict recurrence and the effect of therapy. Reliable tumor markers have been described for colon carcinoma, hepatomas, and other tumors, but no reliable marker has been identified to monitor the course of malignant melanoma. Recently, the plasma level of lipid-bound sialic acid (LASA P) has been described as reflecting an alteration in the surface membrane of cancer cells. An attempt was made to correlate the LASA-P level, along with the serum level of neuron-specific enolase, a glycolytic enzyme specific to cells of neuroectoderm origin including melanocytes, with clinical disease activity with a follow-up to at least 2 years. Two hundred seventy patients had blood samples drawn at various times during their clinical course for assay of LASA-P and neuron-specific enolase. Eighty of the patients (30%) sampled developed a recurrence sometime during their clinical course, whereas another 10 patients had active disease noted at diagnosis with evaluative tumor markers. The sensitivity and specificity of neuron-specific enolase was 27% and 77%, respectively, and cannot be recommended as a marker for melanoma. LASA-P showed a sensitivity of 65%, with 55 patients recurring and having active disease with abnormally high markers and 35 patients recurring or having active disease with normal markers. Specificity of the LASA-P test was 76%. When recurrence was associated with elevated LASA-P levels, the elevated level preceded recurrence by a median of 9.3 months. LASA-P may be a useful marker to follow patients with malignant melanoma. PMID- 1642408 TI - Adjuvant chemotherapy in malignant melanoma using dacarbazine, carmustine, cisplatin, and tamoxifen: a University of South Florida and H. Lee Moffitt Melanoma Center Study. AB - A prospective, nonrandomized trial was performed of the four-drug chemotherapy protocol consisting of dacarbazine, carmustine, cisplatin, and tamoxifen citrate given to high-risk patients for recurrence of melanoma after local regional treatment. The treated patients were consecutively registered and 6 patients who did not elect to be treated served as the control population. Criteria for inclusion in the trial were the presence of four or more lymph nodes positive for metastatic melanoma on regional modal dissection, the presence of metastatic disease in second station lymph node areas such as the iliac basin, greater than 5 cm in maximal diameter tumor burden in the nodal basin, and patients who had resected stage 4 (systemic metastases) disease with clear margins and were rendered free of disease. Actuarial survival curves for the treated group and the control subjects were similar (p = 0.91). There was a definite trend toward an increased disease-free survival for the group receiving adjuvant chemotherapy (p = 0.09). The mean disease-free survival for the control population was 200 days and for the treated group, 600 days. The study suggests a therapeutic benefit for adjuvant chemotherapy treatment of patients with metastatic melanoma who have been rendered free of disease but are at high risk for recurrence. PMID- 1642410 TI - Epidemiology and prognostic factors in malignant melanoma. AB - The rising rate of MM reflects damage to the skin that has been done in the past. If a difference is to be seen prospectively, we must use protection (sunscreens) and have suspicious areas evaluated early in their course so that MM can be treated when curable. Until further research yields a cure for advanced MM, the above approach remains the first line of defense in the fight against this cancer. PMID- 1642409 TI - Treatment of stage IV malignant melanoma with dacarbazine, carmustine, cisplatin, and tamoxifen regimens: a University of South Florida and H. Lee Moffitt Melanoma Center Study. AB - Fourteen consecutive patients with stage IV metastatic melanoma with measurable disease were treated between January 1989 and August 1990 with combination chemotherapy. The chemotherapy regimen (DBPT) included dacarbazine (DTIC) 200 mg/m2/i.v. on days 1 through 3, carmustine (BCNU) 150 mg/m2/i.v. on day 1, cisplatin 25 mg/m2/i.v. on days 1 through 3, and tamoxifen citrate 10 mg p.o. twice daily. This cycle was repeated every 4 weeks. BCNU was given every other cycle. A total of six cycles of chemotherapy were delivered. Patients were then restaged to assess the response. Six concurrent patients during the study period did not elect to undergo chemotherapeutic approach and served as control subjects. When evaluated at 300 days of follow-up, 4 patients had response (3 complete response and 1 partial response), 3 had stable disease, and 7 showed progression. At 300 days of evaluation after chemotherapy, survival appeared significantly increased between treated and nontreated groups, that is, 48% in the chemotherapy group versus 27% in the control group (p = 0.03). Actuarial survival was significantly increased between those who responded to chemotherapy versus the nonresponders. At 300 days follow-up, survival was at 83% in the responders and 22% in nonresponders (p = 0.0002). This study shows that in stage IV disease, systemic chemotherapy appears to make a difference in survival. Attempts to discover better chemotherapy regimens to improve response in patients with stage IV malignant melanoma should continue to be rewarded. PMID- 1642411 TI - Autologous bone marrow transplantation and melanoma: a focused review of the literature. AB - Metastatic malignant melanoma has been regarded traditionally as an aggressive cancer highly refractory to standard doses of chemotherapy. Complete responses to standard chemotherapy are less than 5%. To overcome resistance, autologous bone marrow transplantation has been employed in the treatment of this disease. High dose chemotherapy followed by autologous bone marrow rescue has been associated with increased response rates when compared with standard chemotherapy. A recent survey indicates that at least 283 patients with metastatic melanoma have been treated with this form of therapy thus far. Evaluation of the literature indicates that overall response rates for melanoma patients undergoing autologous bone marrow transplantation range from 46 to 65%, with complete response rates as high as 16%. Although few patients are long-term responders, several patients remain in complete remission for periods of more than one year. Multiple centers are evaluating the utility of high-dose therapy in the high-risk adjuvant setting for patients who present with poor prognosis disease. Data concerning the long term outcome of this therapy are not available. This article reviews the concepts of high-dose therapy followed by autologous bone marrow transplantation, and the outcomes of patients with malignant melanoma who are treated in this manner. PMID- 1642412 TI - Detection of occult lymph node metastases in malignant melanoma. AB - An accurate prediction of the prognosis of melanoma is dependent on the ability to determine the presence or absence of malignant cells in lymph nodes. Our laboratory has developed a method for screening lymph node sections for the presence of micrometastatic disease. The nodes obtained from regional lymphadenectomies are dissected free from surrounding tissue and divided into halves. One-half is subjected to routine histopathological evaluation and the other one-half is disrupted into a single cell suspension and placed into cell culture. Lymph nodes from 19 patients with malignant melanoma were evaluated by tissue culture. Tumor cells were isolated in 125 of the 173 nodes examined. In contrast, only 14 of these nodes were initially found positive for melanoma by routine pathological evaluation. All lymph nodes positive for melanoma by pathological evaluation were also culture positive. Examination by cell culture has led to an upgrade in the stage of disease in 58% of the histologically node negative patients. In addition, 43% of the patients who were histologically node negative but culture positive have recurred, suggesting some clinical correlation. These results indicate that the tissue culture method for detecting micrometastatic lymph node disease may prove more reliable and sensitive than current techniques for determining the presence of occult melanoma. PMID- 1642413 TI - Therapeutic and prognostic considerations of head and neck melanoma. AB - Therapeutic considerations are discussed based on recurrence and survival statistics of 900 patients treated at Duke University Medical Center (Durham, NC). Approximately one-third of all patients developed recurrence. Factors affecting recurrence include tumor thickness, presence of positive regional nodes at diagnosis, and advanced Clark level. Patients with more than one adverse index had even higher rates of recurrence than with one alone. The 5-year survival of all patients after recurrence was 32%. Therapeutic decisions should include considerations that relate to patients' recurrence patterns and survival curves. PMID- 1642414 TI - Metastatic melanoma with an unknown primary. AB - An infrequent initial presentation for malignant melanoma is the diagnosis of metastatic disease without a history of an obvious primary lesion. Confusion exists in the literature concerning the workup, treatment, and prognosis of the unknown primary melanoma. A retrospective, computer-aided chart review of 580 consecutively registered patients with melanoma at the University Treatment Center (Tampa, FL), identified 18 patients with an unknown primary presentation. There were 10 males and 8 females with a mean age of 38.4 years. Ninety-four percent of the patients were diagnosed with metastatic disease in a nodal basin, whereas 1 patient had a resected isolated lung mass as the initial presentation. In the patients who presented after having a biopsy of a single positive node for diagnosis, more disease was recovered in the nodal basin with a formal node dissection in 59% of the patients. Actuarial survival curves were constructed for the group with unknown primary melanoma. As a control population, survival curves were constructed of the subpopulation of patients with melanoma who had a known primary and had stage III (regional nodal disease) at diagnosis. There was no difference in survival between those with known and unknown primary melanoma (p = 0.96). PMID- 1642416 TI - "Thin" malignant melanoma: risk factors and clinical management. AB - Thin melanomas can metastasize and can be lethal. Six hundred eighty-one patients with melanomas less than 0.76 mm thick have been evaluated, and are reviewed in this study and discussed in the context of a literature review. Among those referred without metastatic disease (583 patients), 4.8% metastasized after a mean follow-up of 3.6 years. Among those referred with metastatic disease (98 patients), mortality was 35% after a mean follow-up of 5.9 years. Male patients (p less than 0.04) and patients with axial primary lesions (p less than 0.05) had increased risk of metastasis. Severe histological regression was present in 40% of primary lesions that metastasized and only 17% of similar lesions that did not (p less than 0.001). Increased age was associated with increased local skin metastases, but not with increased nodal or distant metastases. A prognostic model was designed that identifies a low-risk population with an actuarial risk of metastasis at 10 years that is less than 3%. High-risk patients have an actuarial risk of metastasis of 11% at 5 years and 22% at 10 years (p = 0.0084). Identifying high-risk and low-risk patients with thin melanomas may improve guidelines for the application of adjuvant therapies to this population. New approaches to this problem include use of molecular biology techniques, immunohistochemistry, and varied methods of histological sectioning. PMID- 1642415 TI - Anorectal melanoma: clinical characteristics and the role of abdominoperineal resection. AB - Twenty-four patients with primary anorectal melanoma diagnosed since 1974 have been retrospectively studied. The most common presenting symptom was rectal bleeding, typically misdiagnosed as hemorrhoids. Progressive disease most commonly presented as a large pelvic mass, diffuse bilateral pulmonary nodules, or diffuse liver metastases. Twenty-one patients (88%) died of their disease; none survived more than 6 years. Among the patients who have died of their disease, mean survival was 2.2 years. Among assessable stage I patients initially managed with abdominoperineal resection (APR), 50% developed recurrent local regional disease (mean disease-free interval = 23 months), compared with 100% of those managed with more limited surgery (mean disease-free interval = 16 months). Even after APR, however, distant metastases were common, and there was no prolongation of survival for patients treated with APR. Primary melanoma of the anorectum has a high metastatic potential and carries a grave prognosis. APR appears to have some effect in controlling local and regional disease, but prolongation of survival will depend both on earlier diagnosis and on development of more successful therapeutic approaches. PMID- 1642417 TI - The dilemma of the dysplastic nevus. PMID- 1642419 TI - [Radiological aspects of acoustic neurinoma]. AB - For a long time CT constituted the technique of choice for the investigation and pretreatment staging of acoustic neuroma. It is sometimes inadequate especially for defining the extra-axial site of a tumour or for identifying small lesions. Today, any case of suspected acoustic neuroma should undergo first-line MR studies. MR identifies almost all extra-axial lesions, clearly visualises small lesions and provides a satisfactory pretreatment staging in the majority of cases, acoustic neuroma presents a signal intensity identical to or lower than that of the brainstem with a high intensity signal on T2-weighted SE sequences and post-gadolinium T1-weighted SE sequences, generally with a mixed intra- and extra-meatal location and eccentric in relation to the anterior border of the porus. PMID- 1642418 TI - Malignant melanoma and pregnancy. AB - Among 100 patients diagnosed with melanoma during pregnancy and followed a mean of 6.8 years, when compared with a nonpregnant female population, there was a significantly shorter disease-free interval for the pregnant group. Median disease-free intervals were 5.8 and 11.9 years, respectively. The time to development of lymph node metastases was shorter in the pregnant patients (p = 0.015). Nodal metastases developed in 48% of the pregnant patients and only 26% of the nonpregnant patients, at 10 years. Multivariate analysis demonstrated that pregnancy at diagnosis was significantly associated with the development of metastatic disease (p = 0.008), when controlling for tumor site, thickness, and Clark level. Pregnancy, however, was not a risk factor for patient mortality. The literature continues to be split on the role of pregnancy in melanoma; however, most recent series show no difference in survival. Multiple studies have failed to show significant effects of female hormones on melanoma cells or on the incidence or progression of melanoma. PMID- 1642420 TI - [Auditory evoked potentials and tumor of the cerebellopontine angle]. AB - The technique of auditory evoked potentials evaluates the auditory pathways along the vestibulocochlear nerve and in the brainstem. The authors stress the importance of this examination in the diagnosis of tumours of the cerebellopontine angle and they discuss its place in relation to radiological investigations. PMID- 1642421 TI - [Vestibular studies: current status, prospects]. AB - Equilibrium is based on gaze stabilization. Clinical examinations currently test, individually the three components involved in equilibrium: vestibular, visual and proprioception. New investigations are being developed to test equilibrium dynamic conditions. After briefly reviewing vestibular physiology, under the authors discuss the various tests of vestibular function and equilibrium. PMID- 1642422 TI - [Rare tumors of the cerebellopontine angle]. AB - Tumours of the cerebellopontine angle are essentially benign in adults, are generally treated surgically and require a preoperative assessment as precise as possible. MRI simplifies the diagnostic assessment; it is indicated as the first line investigation and is usually sufficient whenever a tumour of the posterior cranial fossa is suspected. Acoustic neuromas represent 75% of all tumours of the cerebellopontine angle. Other tumours are rare and essentially consist of meningioma, detected in 10 to 14% of cases and cholesteatoma in 1 to 5% of cases. Cholesteatoma, with a pathognomonic appearance, must be distinguished from arachnoid cyst. Other tumours are exceptional. The authors define the diagnostic criteria based on their experience and present a recent review of the literature. PMID- 1642423 TI - [3D imaging of the labyrinth: application to candidates for cochlear implant]. AB - Cochlear implantation is a treatment for profound bilateral cochlear hearing loss. Two broad varieties of cochlear implants are used: single or multichannel device (22- channel) inserted either into the cochlea (tympanic ramp) or on the promontory on round window Imaging modalities have to predict cochlear patency prior surgery, an essential factor for choosing between intra or extra cochlear implant. Since March 1991, we have investigated 23 implant candidates to evaluate cochlear patency prior surgery, 6 patients underwent surgery: 4 had a multichannel and 2 had a monochannel electrode. Both CT and MRI play a role in pre operative study. CT easily predicts cochlear ossification and labyrinthine malformations MRI (3 D applications) with T 2 Weighted images, one millimeter thick, more clearly depicts labyrinthine liquid and can predict cochlear fibrosis before ossification. PMID- 1642424 TI - [Petrous surgical approaches in tumors of the cerebellopontine angle]. AB - Three petrous incisions, performed by an ENT-neurosurgery team, can be used for the resection of tumours of the cerebellopontine angle: transpetrosal incisions (posterior translabyrinthine and transcochlear) which provide large access to the IAM and the posterior surface of the petrous bone, but they sacrifice hearing. The suprapetrosal incision (reserved for tumours in the meatus) and the mastoidoretrosigmoid incision (for tumours less than or equal to 20 mm) preserve the labyrinth in an attempt to preserve hearing. The principal objectives of surgical resection of tumours of the cerebellopontine angle (85% of which are acoustic neuromas) are total resection (to preserve the vital prognosis) and preservation of facial nerve function. Attempts to preserve hearing must be confined to cases selected by a complete clinical otological and audiometric examination. PMID- 1642425 TI - [MRI techniques for the study of the temporal lobe and its environment]. AB - The MR study of the temporal lobe and its environment requires a good knowledge of the anatomy in order to select the views adapted to the disease investigated. The authors propose a series of protocols according to the region examined. An understanding of the principles of MR sequences is also essential to avoid the problems of investigation associated with this complex anatomical region. The principal sequences are reviewed together with their advantages and disadvantages. PMID- 1642426 TI - [Mycotic sinusitis. Contribution of x-ray computed tomography]. AB - The authors present three cases of fungal sinusitis. Fungal sinusitis is a relatively rare disease that affects more commonly immunosuppressed and diabetic individuals. The radiographic signs are non-specific. Nevertheless, some CT findings are highly suspicious: unilateral lesions of one or more sinuses; nodular mucoperiosteal thickening, and, or focal areas of bone destruction; very dense, intrasinus concretions. Air-fluid levels are very uncommon, and when present suggest a nonfungal bacterial infection. In most cases, a combination of these findings suggests fungal disease. The clinical hallmark is chronic sinusitis that fails to respond to antibiotic therapy. PMID- 1642427 TI - [Subcondylar mandibular fracture]. AB - Mandibular fractures are frequent lesions which are classified into 6 groups according to the site of the fracture. Condylar fractures are primarily due to a direct blow to the symphysis menti. Medical imaging must be able to identify the type of fracture, its intra- or extra-articular site and the associated displacement of the condyle, the fundamental element in deciding treatment. The action of the masticatory muscles on one of the bone fragments may be responsible for an unstable fracture, leading to disturbances of consolidation (pseudarthrosis). Anterior bilateral fractures can be life-threatening due to ptosis of the tongue. PMID- 1642428 TI - [Cholesterol granuloma. Review of the literature apropos of a case]. AB - MRI allows the diagnosis of cholesterol granuloma in the presence of a non contrast-enhanced, erosive solid mass of the apex of the petrous bone or middle ear. Cholesterol granuloma has a suggestive low signal intensity on T1 and T2 weighted sequences (cholesterol crystals, haemoglobin degradation products). These specific features eliminate the principal CT differential diagnoses, particularly cholesteatoma. MRI is also useful for follow-up of treatment. PMID- 1642429 TI - [Symptomatic trigeminal neuralgia caused by venous angioma of the posterior fossa]. AB - Any atypical trigeminal neuralgia requires etiological investigation. The authors report a case of a trigeminal neuralgia (V2) due to an angioma associated with two cavernomas. PMID- 1642430 TI - [Biological roles of free radicals: introduction]. AB - Free radicals are produced during cellular oxidations. The primary ones are superoxide anions (O2-) and hydroxyl radicals (OH). They generate in vivo various secondary radicals. Radical mechanisms are invoked in a number of biological processes including, phagocytosis, ischemia or ageing. PMID- 1642431 TI - [Extracellular matrix and vascular pathologies. Role of proteases and oxygenated free radicals]. AB - Vessel walls contain several types of mesenchymatous cells and many representatives of the 4 groups of macromolecules of the extracellular matrix secreted by those cells. Under normal conditions, a proportion of the macromolecules of the vascular wall is broken down by the neosynthesis of an equivalent amount of the same macromolecules which are then integrated into functional structures. Under pathological conditions, an excessive amount of macromolecules is broken down by proteases and free radicals, without any compensatory increase in biosynthesis and without the integration of biosynthesised compounds into functional structures. Thus, for example, a varicose saphenous vein may lose as much as 60 per cent of the collagen of its wall. Attempts at symptomatic treatment designed to combat this loss of substance, a notable cause of weakening of he vessel wall, are based upon three principles: inhibition of catabolic enzymes, chiefly proteases (e.g. leucocyte elastase), responsible for excessive breakdown; uptake of oxygenated free radicals; "substrate protection" designed to preserve undamaged fibrous proteins and to help the integration of neosynthesized compounds into functional structures. Only medications which act as "substrate protectors" are capable of coping at one and the same time with the effects of proteases and those of oxygenated free radicals. PMID- 1642432 TI - [Oxygenated free radicals and vascular pathology]. AB - Oxygen free radicals are used as a weapon by neutrophil morphopolynuclear cells, monocytes and macrophages against bacterial attacks. They do interact with arachidonic acid cascade catabolism that means they stimulate too, platelet cells and endothelial cells activity (EDRF is indeed "NO"). They prime all along inflammatory process and thrombosis which are main items of the pathology of vessels. PMID- 1642433 TI - [Myxoma of the right atrium. Apropos of 10 surgically treated cases]. AB - In a series of 100 patients with intracardiac myxoma, the lesion was in the right atrium in 10 cases. The authors attempt to define the particular features of right atrial myxoma in terms of clinical aspects, outcome and pathology. The diagnostic difficulty raised by complex clinical pictures (including right ventricular failure, pseudopericardial forms and forms with a predominance of systemic problems) has now been resolved by imaging and, above all echocardiography. Consequences for the right side of the heart may involve the pulmonary artery with myxomatous emboli causing multiple fusiform aneurysms and pulmonary hypertension, or, more rarely, the tricuspid (with need for valve replacement), vena cava (Budd-Chiari syndrome) or atrial septum (right/left shunt). Alongside systemic problems due to interleukin 6, erythrocyte abnormalities are a new feature. Frequent etiological inclusion in a Carney complex explains recurrences and multi-cavity forms. The dominant pathological feature is tumor calcifications, no doubt as a result of the long presymptomatic phase of myxoma. PMID- 1642434 TI - [Clinical and angiographic results of delayed revascularization by angioplasty or bypass after intravenous thrombolysis in myocardial infarction]. AB - Between 1988 and 1990, 150 patients treated for an infarction by intravenous thrombolysis underwent coronary arteriography. Sixty seven were managed by revascularisation by angioplasty (n = 49) or bypass (n = 18) more than 48 hours after thrombolysis. In this delayed revascularisation group, the time before initial fibrinolysis was 114 +/- 55 minutes. The artery responsible for the infarction was patent in 88 per cent of cases at 12 +/- 9 days, with ejection fraction being 56 +/- 12 per cent. Indications for revascularisation were: recurrence of angina, Thallium stress test showing redistribution (n = 9), diffuse lesions (n = 11) or tight (greater than 75 per cent) proximal stenosis without vessel wall sequelae (n = 10). Comparison of the bypass and angioplasty groups showed a lower ejection fraction in the former than the latter (47% VS 58%, p less than 0.01), more frequent three-vessel disease (50% VS 6%, p less than 0.01) and more frequent revascularisation of the anterior interventricular (100% VS 37%, p less than 0.01). There were 2 deaths and 5 recurrences of infarction at one year. Follow-up arteriography was performed between at 2 and 6 months in 72% of the patients: 16 had restenosis after angioplasty and 4 occlusion of the graft after bypass. A second revascularisation procedure was necessary 15 times (14 angioplasties, 1 bypass). The outcome after bypass or angioplasty was favourable in 90% of cases in this group of patients exposed to a recurrence of infarction. PMID- 1642435 TI - [Cardiac toxicity of fluoro-uracil. Typical and atypical aspects. Apropos of 8 cases]. AB - The cardiac toxicity of 5 fluoro-uracil, an antimitotic agent widely used in various protocols, has been known for 16 years. Several cases have been reported in the literature, leading to the suggestion, without formal evidence, that the chief mechanism responsible for this cardiac toxicity is "classical" coronary spasm. However, certain clinical aspects already described may shed doubt on this theory. On the basis of 8 cases, the authors report different clinical pictures all caused by cardiac toxicity of 5FU. It is of interest to note that chest pain with the classically described electrocardiographic changes did not apply in the majority of cases. The commonest pattern was asymptomatic electrocardiographic abnormalities and/or arrhythmias without angina. Among the reported cases, one patient had pain with electrocardiographic abnormalities, recurrent after the withdrawal of 5FU and resistant to maximal medical treatment, despite the absence of any coronary disease or signs of spasm. One patient had a first myocardial infarction, later rechallenge with the drug resulting in failure. In another patient, with known coronary disease, 5FU probably cause cardiogenic shock. In total, some of our cases, as well as other features described in the literature, raise questions as to the pathophysiology of the cardiac toxicity of 5FU. PMID- 1642436 TI - [Leg muscle bed syndrome: medical aspects of chronic forms]. AB - Ninety two patients with lower leg pain of unknown cause underwent intramuscular pressure measurements by the needle technique described by Whitesides. Fifty four patients (59%) were found to have a chronic compartment syndrome. In these patients the intramuscular pressure was significantly increased at rest and after exercise as compared with normal subjects (13) and patients without the syndrome (38). Increased pressure at rest after exercise and a prolonged time for normalisation are the most commonly parameters in diagnosing chronic compartment syndrome. Tissue pressure measurement remains the basis of diagnosis for patients suffering from chronic compartment syndrome, indeed the clinical findings alone were found to be insufficient. Effective treatment consists of reduction of exertional activities or decompression by fasciotomy. The clinical results after fasciotomy were good and consistent with the findings of others. PMID- 1642437 TI - [The single coronary artery]. AB - Single coronary artery is a fairly rare entity which may nevertheless be found in 0.4 per cent of coronary arteriograms. The authors report 3 cases seen in 2 departments of cardiology. In each patient, despite the existence of definite cardiovascular risk factors, this distribution was a factor worsening coronary ischemia, leading to complete thrombosis in one case. Although most often a chance discovery, a review of the literature justifies the attribution to this anomaly of the onset of angina, infarction or even sudden death. PMID- 1642438 TI - [Negativity of the exercise thallium test despite tight stenosis of the common trunk of the left coronary artery]. AB - The authors report a case of severe angina linked to subocclusive ostial stenosis of the common trunk of the left coronary, characterised by the contrast between a very positive stress test on the basis of clinical and electrocardiographic parameters and a negative Thallium stress test. The occasion is taken to review the sensitivity of Thallium stress testing in lesions of the common trunk. PMID- 1642439 TI - [Spontaneous complete rupture of the thoracic aorta. Apropos of a case surgically treated with success]. AB - The authors report the case of a 74-year-old hypertensive man hospitalised with chest pain accompanied by shock and hemo-mediastinum. The diagnosis of spontaneous rupture of the thoracic aorta, suspected by aortic arteriography, was confirmed by thoracic CT scan with injection of contrast medium. Emergency surgery revealed a 4 cm longitudinal linear tear of the horizontal aorta, with neither dissection nor aneurysm. Simple suture during extra-corporeal circulation with normothermia and the heart beating, was successful after prolonged postoperative intensive care. This case of complete and spontaneous acute rupture of the horizontal thoracic aorta appears to be the first to have been successfully treated surgically. PMID- 1642440 TI - [Adjustment of double-chamber pacemakers in VDD mode by measurement of thoracic electric bio-impedance]. AB - An optimal atrioventricular interval (AVI) was sought in 6 patients with a double chamber pacemaker by an non-invasive technique: measurement of stroke volume by thoracic bioimpedance. This method proved to be easy and reliable in practice when there was only one pacing spike (VDD mode). It confirmed the existence of a variable optimal AVI according to individual patients: 250 ms (3 patients), 200 250 ms (1 patient), 150 ms (1 patient), 75-100 ms (1 patient). The value of optimal AVI is unpredictable since it depends upon individual electrophysiological and hemodynamic parameters. In a patient with severe mitral incompetence, Echo-Doppler provided evidence of end-diastolic ventriculo-atrial regurgitation at middle and long AVI, while a short AVI enabled elimination of end-diastolic regurgitation and a 15.45 per cent improvement in stroke volume. In two patients with a long optimal AVI (250 ms), a programmed short AVI (75 ms) paradoxically appeared to be more favourable than a middle AVI (150 ms). PMID- 1642441 TI - [Comparison of the efficacy/tolerability ratio of cibenzoline and propafenone in the treatment of ventricular arrhythmia]. AB - Cibenzoline (C) was compared with propafenone (P) in 18 adult patients (7 women and 11 men) aged 50 +/- 7 in double-blind, placebo-controlled crossover trial. After a therapeutic wash-out period corresponding to 5 times the half-life of previous anti-arrhythmic drugs, patients with more than 100 premature ventricular contractions (PVC) per hour in two 24 hour Holter records obtained at an interval of 7 days were treated in succession and after randomised by C (390 mg/day in 3 divided doses) and P (900 mg/day in 3 divided doses) for a period of two weeks, each active sequence being followed by a two week wash-out period. Efficacy (based upon the decrease in PVC/hour in a 24 hour Holter) and tolerability were evaluated at the end of each sequence, with samples drawn at the same times for assay of the study drugs. Three patients dropped out of the trial, 1 with each active drug (for epigastric pain) and 1 with dummy. No significant difference was seen between the two drugs regarding the decrease in the total number of PVC/hour in the 15 patients completing the cross-over protocol. A reduction in PVC/hour of more than 70 per cent was seen in 7 patients with C and in 9 patients with P. C was better tolerated than P on the basis of both clinical and electrocardiographic parameters. One patient developed troublesome adverse reactions with C as compared with 4 patients in the case of P. A more than 20 per cent increase in QRS was seen in 7 patients with C and in 10 patients with P, the figures for PR being 2 and 6 patients respectively. One patient showed a proarrhythmic effect with P. Plasma levels of C were significantly higher in responders (328 +/- 149 ng/ml) than in non-responders (137 +/- 41 ng/ml, p less than 0.05). No significant difference was found concerning plasma levels of P (578 +/- 477 ng/ml compared with 646 +/- 457 ng/ml, p greater than 0.05). In conclusion, the efficacy/tolerability ratio in this population with a low risk of serious rhythm events appeared to be better with C than with P. PMID- 1642442 TI - The neonatal detection of cystic fibrosis by measurement of immunoreactive trypsin in blood. PMID- 1642443 TI - Measurement of aluminium in clinical samples. AB - Measurement of aluminium in clinical samples is important for the protection of patients with chronic renal failure, and for investigations of dementia. The types of specimen that need to be analysed include body fluids and tissues, dialysis fluids, water and foods and the concentrations that may be found can range from around 1 microgram/L to several mg/L. Although techniques must afford exceptional sensitivity they will also be susceptible to the effects of external contamination and it is imperative that those involved with the analysis, from sample collection through to the determination, ensure that precautions are taken to prevent undue addition of the metal. Of the methods that may be used ETAAS is clearly the most appropriate. Great care is required to achieve reliable performance but with experienced personnel very good results can be obtained. Regular reviews of recent analytical developments are presented in the Atomic Spectrometry Updates series and these are recommended to those who may wish to look for further information. PMID- 1642444 TI - Abnormal endogenous carbon monoxide production in children with ineffective erythropoiesis. AB - The aim of this study was to evaluate the extent of endogenous carbon monoxide production in subjects with ineffective erythropoiesis. Carboxyhaemoglobin concentrations were measured in eight transfused and eight nontransfused thalassemic patients. Measurements were made on venous blood collected under controlled conditions and were corrected by simultaneous measurement of HbF levels. Nontransfused thalassaemic patients with abnormal erythropoiesis were found to have elevated levels of carboxyhaemoglobin, significantly higher than those found in transfused subjects, as well as decreased cardiac performance. It is important to consider carboxyhaemoglobin levels in planning transfusion programmes. PMID- 1642445 TI - Reference values for urinary HMMA, HVA, noradrenaline, adrenaline, and dopamine excretion in children using random urine samples and HPLC with electrochemical detection. AB - Random urine samples were collected from 305 children aged from birth to 14 years and the values of hydroxymethoxymandelic acid, homovanillic acid, noradrenaline, adrenaline, and dopamine were measured by high-performance liquid chromatography with electrochemical detection. The results were reported relative to the urinary creatinine concentration and the values declined progressively with increasing age for each analyte with the exception of adrenaline. The results for each age group were not normally distributed and all values except outliers were retained in determining the upper reference limits. PMID- 1642446 TI - Comparison of seven formulae and isoelectrofocusing for determination of intrathecally produced IgG in neurological diseases. AB - Seven different formulae and agarose isoelectrofocusing (AIF) using immunolabelling for IgG were compared for their ability to discriminate between intrathecally produced IgG and transudated IgG in cerebrospinal fluid. All reference limits were set to a specificity of 97.5% (reference group, n = 211). The probability of a positive test (p+) was evaluated for 112 patients with multiple sclerosis (MS), 42 with meningitis, 114 with noninflammatory diseases affecting the central nervous system (CNS), 23 with Guillain-Barre syndrome, and 56 with various diseases not affecting the CNS. Agarose isoelectrofocusing had the best diagnostic sensitivity (93%) for MS, combined with a low p+ (0-19%) for other diseases. Among the formulae, the IgG extended index and Reiber's hyperbolic formula were equivalent, giving high (75-79%) diagnostic sensitivity for MS combined with low p+ (4-22%) for other diseases. All other formulae, although sensitive for MS, had a higher rate of false positive results. PMID- 1642447 TI - Nephelometric determination of total protein in cerebrospinal fluid and urine using benzalkonium chloride as precipitation reagent. AB - Four different protein precipitants, namely trichloroacetic acid, sulphosalicylic acid, benzethonium chloride and benzalkonium chloride, were used to estimate the total protein concentration in cerebrospinal fluid and urine by nephelometry. Protein determinations for 50 cerebrospinal fluid samples and 100 urine samples were compared with values obtained by a trichloroacetic acid-Ponceau S spectrophotometric method. All methods were correlated well, but total protein results using acid precipitants were usually lower, while results obtained using benzethonium chloride were generally higher, than results obtained by the trichloroacetic acid-Ponceau S method. Anomalous results were obtained for some urine samples with benzethonium chloride, but not with benzalkonium chloride. Assays using benzalkonium chloride as precipitating reagent showed good precision and closest agreement with the trichloroacetic acid-Ponceau S dye-binding method. The use of benzalkonium chloride as precipitant is recommended for automated cerebrospinal fluid and urine protein estimations by nephelometry. PMID- 1642448 TI - A simple method for the measurement of different forms of alpha 1 proteinase inhibitor in the faeces of patients with Crohn's disease. AB - Alpha-1 proteinase inhibitor (alpha 1PI), formerly named alpha 1-antitrypsin, is excreted in the faeces of patients with Crohn's disease as isoforms clearly separated by SDS-PAGE and immunoblot analysis. Relapses in Crohn's disease are generally associated with the appearance in faeces of M(rs) 51,000 and 45,000 glycosylated forms of alpha 1PI, as compared with normal subjects and most of the patients in quiescent phases of their disease who excrete an M(r) 38,000 unglycosylated form of alpha 1PI. We used their differential Concanavalin-A reactivity to design a specific test. The proposed assay is potentially helpful for the follow-up of patients under therapy and for early recognition of attacks of Crohn's disease. PMID- 1642449 TI - Within-subject and between-subject biological variation of prothrombin time and activated partial thromboplastin time. AB - The within-subject and between-subject biological variation of prothrombin time (PT) and activated partial thromboplastin time (APTT) have been studied in a group of 19 women and 20 men over a period of 9 months. All measurements were performed with a mechanical coagulometer. The between-subject coefficients of variation were 6.8% for PT and 8.9% for APTT. The medians and the 90th percentiles of within-subject coefficients of variation were 1.7% and 5.9%, respectively, for PT, and 0.0% and 6.1% for APTT. These data were used to calculate the critical difference for significant change detection and the desirable between-day imprecision. PMID- 1642450 TI - Prevalence of haemoglobin variants in a diabetic population and their effect on glycated haemoglobin measurement. AB - The measurement of glycated haemoglobin (glycated Hb) by automated high pressure liquid chromatography enabled the prevalence of haemoglobin variants (Hb variant) to be determined in a large diabetic population within Leeds, UK. There were 16 patients showing a Hb variant amongst a total of 5300 diabetics, the majority of the variants being HbA/S traits. There were also 13 patients showing a slightly raised HbF in the range of 2% to 5%. A multi-centre study was carried out by distributing blood specimens from some of the patients with Hb traits. Significant differences in the percentage of glycated Hb were observed relating to the methodology used. However, glycated Hb is used to monitor glycaemic control and laboratories must be aware of Hb variant interferences on their methods. Also, screening for Hb variants should be considered for the at risk groups of diabetic patients. PMID- 1642451 TI - Defective collagen metabolism in Saudi patients with hernia. AB - Fibroblastic cell cultures were derived from the hernial sac and some of the surrounding muscles (rectus sheath, internal oblique, and/or cremasteric muscle) of 130 Saudi patients with different types of herniation, and from 21 control subjects. The rates of cell proliferation were studied for 39 days. Results suggested decreased rates of proliferation of cells derived from patients compared to controls. In vitro studies of the rates of incorporation of 14C proline into the muscle biopsies revealed decreased rates of label incorporation in the samples derived from patients compared to controls. However, no differences were detected between rates of collagenase activities of the biopsies obtained from patients compared to those of controls. These findings suggest that collagen synthesis is probably defective in the studied group of Saudi patients with hernia. PMID- 1642452 TI - Serum fructosamine concentration in patients with nephrotic syndrome and with cirrhosis of the liver: the influence of hypoalbuminaemia and hypergammaglobulinaemia. AB - We have investigated the influence of variation of the concentrations of serum albumin and immunoglobulins on serum fructosamine concentration in 33 patients with nephrotic syndrome, and 18 patients with cirrhosis of the liver. Protein alterations were evident in these patients and they were compared with 109 normal subjects, 43 patients with type II diabetes mellitus and nine diabetic patients with nephrotic syndrome. The mean serum fructosamine concentration in diabetic patients (2.76 +/- 0.53 mmol/L) was significantly increased (P less than 0.001) by comparison with normal subjects (1.93 +/- 0.20 mmol/L) and the other patients studied. Patients with diabetic nephropathy had higher (P less than 0.01) serum fructosamine concentrations (2.23 +/- 0.54 mmol/L) than non-diabetic patients with the nephrotic syndrome (1.57 +/- 0.37 mmol/L) but remained with the normal range. Positive correlations were observed between fructosamine and immunoglobulins G and M in nephrotic and cirrhotic patients. Serum immunoglobulin A was also directly correlated with serum fructosamine in patients with cirrhosis of the liver. An inverse correlation between albumin and fructosamine in serum of patients with cirrhosis of the liver was also noted. We conclude that the fructosamine assay is not useful in the assessment of glycemic control in patients with cirrhosis of the liver, nephrotic syndrome or in any other clinical situation in which protein metabolism is altered. PMID- 1642453 TI - Dependence of measured ionized calcium on protein concentration as measured by three ion-selective electrodes. AB - A positive effect of protein on the measurement of ionized calcium in serum by ion-selective electrodes (ISEs) has been previously reported and the present study confirms this finding. Ionized calcium in serum was measured in the presence of increasing protein concentrations induced by venous stasis in 17 healthy volunteer subjects. Ionized calcium was measured using two commercial analysers, a Radiometer ICA2 analyser and a Baker Analyte+2 analyser, and a calcium cell devised by Covington for the calcium reference method (CRM). Both commercial analysers used charged ionophores and the CRM used a neutral carrier ionophore in the selective membrane. A small but significant rise in ionized calcium with increasing protein was measured on all analysers. Substitution of isotonic KCl for saturated KCl in the reference electrode of the CRM resulted in significantly reduced values for ionized calcium in paired serum samples when measured using the isotonic salt bridge. This study supports the premise that the positive effect of protein is related to the salt bridge concentration of the reference electrode rather than the ISE membrane composition. PMID- 1642454 TI - Auditing quality control procedures in a chemical pathology laboratory--a multiple regression analysis. AB - We undertook a retrospective analysis of the monthly test rejection rates and the monthly external quality assessment scheme performance indices for our laboratory's two automated analysers, and examined the association of these variables with measures of laboratory workload, manpower, staff training, instrument servicing, seasonal and temporal factors and changes of calibration, method and assigned internal quality control values. Using multiple linear regression and stepwise multiple linear regression, we found that test rejection rates differed significantly between instruments, and were highest on the instrument performing the widest variety and lowest volume of tests. On that instrument, rejection rates were significantly associated with the introduction of new staff and laboratory manpower levels, and also showed a highly significant trend upwards over the study period, independent of the effects of the other variables examined. External quality assessment scheme performance indices showed small trends over the study period. They were not related to the test rejection rates on either analyser but also showed a significant association with the introduction of new staff and a small but significant association with laboratory workload. We conclude that the training and introduction of new staff and decreased laboratory manpower levels may significantly increase the level of test rejection, and adherence to appropriate quality control protocols effectively maintains the quality of the laboratory's results, but may not be completely successful in filtering out the effects of some assignable causes of variation in test results. It is suggested that clinical laboratories use the statistical approach adopted here to identify factors which may be adversely affecting quality performance and running costs and to provide evidence that quality control procedures are both cost- and quality-effective. PMID- 1642455 TI - Human cardiac muscle magnesium and potassium concentrations: can skeletal muscle, mononuclear blood cells, erythrocyte and plasma concentrations provide a surrogate measure? PMID- 1642456 TI - Failure of an immunometric assay to detect elevated creatine kinase MB isoenzyme. PMID- 1642457 TI - The use of C-reactive protein in the evaluation of chest pain of cardiac origin. PMID- 1642458 TI - Hyperparathyroidism in pregnancy: three case reports. PMID- 1642459 TI - The measurement of parathyroid hormone. PMID- 1642460 TI - Antibody interference in free thyroxine assays. PMID- 1642461 TI - Spontaneous remission of a third-nerve palsy in meningeal lymphoma. AB - We report on a patient with spontaneous remission of a third-nerve palsy who was subsequently found to have meningeal lymphoma. Initial magnetic resonance images (MRI) showed bilateral enhancement of the third nerves. Follow-up MRI 7 months later, without treatment, showed complete resolution. One year after initial presentation, the patient developed multiple lumbosacral radiculopathies and examination of a nerve root biopsy specimen disclosed a B-cell lymphoma. Serial cerebrospinal fluid analyses over the previous year showed occasional atypical cells, later found to resemble closely the biopsy cell type. We conclude that meningeal lymphoma may have a protracted course, with spontaneous remission of both clinical and neuroimaging findings. PMID- 1642462 TI - Dystonia induced by combined treatment with L-dopa and MK-801 in parkinsonian monkeys. AB - We examined whether the N-methyl-D-aspartate antagonist MK-801 (dizocilpine) would reverse parkinsonism or potentiate the effects of L-dopa in primates treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In contrast to its effect in rodent models, treatment with MK-801 (0.1 mg/kg) caused bradykinesia and ataxia in parkinsonian primates, but no locomotor stimulation. Coadministration of MK-801 (0.1 mg/kg) with L-dopa (20 mg/kg) induced marked dystonia accompanied by bradykinesia and ataxia. Dystonia was not induced by either treatment given alone. These findings indicate that MK-801 should not be advocated as an adjunct to dopamine agonist therapy in Parkinson's disease. PMID- 1642463 TI - Magnetoencephalographic localization of epileptic cortex--impact on surgical treatment. AB - A 24-channel, planar, superconducting quantum interference device gradiometer, sampling a fourth of the head surface over brain tissue, was used to determine the site of an epileptic focus in a 36-year-old woman with intractable complex partial epilepsy. The other presurgical findings appeared divergent: a large arachnoid cyst over the right parietal convexity, dissimilar interictal electroencephalographic patterns, and several neuropsychological dysfunctions. The equivalent current sources of magnetoencephalographic spikes were in the right posterior temporal region of the cortex, 4 cm apart from the cyst. Surgical exploration of the area pinpointed by magnetoencephalography revealed a pachygyric patch of cortex displaying focal discharges on the electrocorticogram. After resection, a dramatic reduction of seizures occurred. The good agreement between electrocorticography and magnetoencephalography warrants future investigation of multichannel magnetoencephalography as a potential alternative to invasive presurgical recordings. PMID- 1642464 TI - Parkinsonism-inducing neurotoxin MPP+: uptake and toxicity in nonneuronal COS cells expressing dopamine transporter cDNA. AB - Expression of a cloned dopamine transporter complementary DNA in COS cells allows these primate kidney cells to accumulate the parkinsonism-inducing neurotoxin metabolite MPP+ (1-methyl-4-phenylpyridinium) avidly, and MPP+ toxicity results. By documenting that the dopamine transporter can confer MPP+ sensitivity to nonneural cells, these results highlight the key role that this transporter could play in mechanisms underlying parkinsonism. PMID- 1642465 TI - Treatment strategy for the corticocortical neuron pathology of Alzheimer's disease. PMID- 1642466 TI - Lhermitte-Duclos disease and Cowden disease: a third case. PMID- 1642467 TI - Mitochondrial oxidative phosphorylation defects in Parkinson's disease. PMID- 1642468 TI - Increased signal in basal ganglia and white matter on magnetic resonance imaging in Creutzfeldt-Jakob disease. PMID- 1642469 TI - Motor dyscontrol in narcolepsy: rapid-eye-movement (REM) sleep without atonia and REM sleep behavior disorder. AB - Narcolepsy involves abnormalities of rapid-eye-movement (REM) sleep, including a short latency to the onset of REM sleep, hypnagogic hallucinations, and sleep paralysis. In addition, persistence of muscle tone by electromyographic criteria or excessive muscle twitching during REM sleep or both have been reported in treated and untreated narcoleptic patients. We report that another previously described abnormality of REM sleep, REM sleep behavior disorder, may also be a symptom of narcolepsy. This disorder was found in 10 narcoleptic patients during routine clinical evaluations involving polysomnography and multiple sleep latency tests. During REM sleep, 7 additional narcoleptic patients displayed persistent muscle tone and/or excessive twitching, which we believe to be subclinical components of REM sleep behavior disorder. These 17 patients, diagnosed by established criteria for narcolepsy and for REM sleep behavior disorder, ranged in age from 8 to 74 years. Seventy-one percent were male. Narcolepsy and REM sleep behavior disorder most commonly emerged in tandem. In 3 patients, treatment of narcolepsy-cataplexy with stimulants and tricyclics either induced or exacerbated REM sleep behavior disorder. PMID- 1642470 TI - Morphometry, histopathology, and tomography of cerebral atrophy in the acquired immunodeficiency syndrome. AB - Patients with the acquired immunodeficiency syndrome (AIDS) commonly display evidence of gross cerebral atrophy, but its true incidence and pathophysiology in the general AIDS population are unknown. In this study, we measured cerebrospinal fluid (CSF) spaces in 64 consecutively autopsied patients with AIDS, compared them with age-matched non-AIDS subjects, and correlated them with the microscopic neuropathology at autopsy. Thirty-seven of the patients with AIDS (58%) had a CSF space index greater than two standard deviations above the mean of the age matched control subjects. CSF spaces were expanded the most in frontal and temporal lobes; ventricular spaces were expanded more than sulcal spaces. Regression analysis between age and the measured CSF indexes showed that practically none of the deviation in patients with AIDS could be explained by age related atrophy. Patients with atrophy were much more likely to have human immunodeficiency virus type 1-associated histopathological changes in their brains, but the relationships were too weak to establish the microscopic cause of the atrophy. Measurement of CSF spaces in antemortem computed tomographic (CT) scans from 47 of the patients with AIDS revealed the same regional pattern of brain wasting. CT diagnosis of cerebral atrophy was strongly concordant with the postmortem diagnosis, but its severity was diagnosed slightly more conservatively at autopsy. Thus, quantitative analysis of CSF spaces in a robust sampling of patients with AIDS confirms that cerebral atrophy is a sensitive, common, and frequently subtle indication of central nervous system human immunodeficiency virus type 1 infection that may occur independently from any single specific microscopic abnormality. Its presence, severity, and regional pattern are detected with reasonable consistency using CT scanning. PMID- 1642471 TI - Physiological abnormalities in hereditary hyperekplexia. AB - Five patients from a kindred with hereditary hyperekplexia had physiological testing. The surface-recorded electromyographic pattern of audiogenic muscle jerks was identical to that of the normal acoustic startle reflex. Testing at graded stimulus intensities indicated an increase in the gain of the acoustic startle reflex. Nose-tap stimuli resulted in short-latency generalized electromyographic bursts that were similar to the R1 component of the blink reflex. Electrical stimulation of peripheral nerves elicited a pattern of generalized muscle jerks that was similar to that of the acoustic startle reflex. Somatosensory evoked potentials, brainstem auditory evoked potentials, and cortical auditory evoked potentials were normal. The primary physiological abnormality in hereditary hyperekplexia is widespread elevated gain of vestigial withdrawal reflexes in the brainstem and possibly the spinal cord, most likely resulting from increased excitability of reticular neurons. PMID- 1642472 TI - Neonatal idiopathic cerebral venous thrombosis: an unrecognized cause of transient seizures or lethargy. AB - Seven neonates who presented with either lethargy (four infants) or seizures (three infants) were found by magnetic resonance (MR) phase imaging to have idiopathic cerebral venous thrombosis (CVT). Examination showed only hypotonia or hyperreflexia. The presence of CVT was suggested by unenhanced cranial computed tomographic (CT) scans. Conventional MR T1- and T2-weighted images often indicated more extensive thromboses than were suggested by cranial CT. In all infants, MR phase imaging confirmed thromboses by establishing absence of blood flow in cerebral veins or sinuses. No infant received anticoagulation. Lethargy slowly resolved and seizures did not recur. Normal development has been observed thus far in brief follow-up. The occurrence of seven infants with idiopathic neonatal CVT within a 3-month period indicates that CVT may be a cause of neonatal seizures or lethargy of unclear cause. MR phase imaging provides a powerful, noninvasive means of confirming the diagnosis. Treatment with anticoagulants does not appear necessary. PMID- 1642473 TI - An abnormality of plasma amyloid protein precursor in Alzheimer's disease. AB - beta A4 amyloid deposition in the brain, which is characteristic of Alzheimer's disease (AD), may result from either overexpression of the amyloid protein precursor (APP) or failure of APP to be correctly processed. A blood marker reflecting this abnormal metabolism would be of diagnostic value and would provide a means of monitoring the efficacy of therapeutic interventions. We analyzed immunoblots of plasma APP enriched by heparin-Sepharose chromatography from patients with moderate to severe AD dementia (n = 34) and control subjects (n = 77) and found an approximately 50% increase in the proportion of 130-kd APP species in patients with AD (p less than 0.001), no difference in the 110-kd form, a 15 to 30% decrease in the 65-kd form (p less than 0.001), and a 20 to 35% decrease in the proportion of 42-kd APP (p less than 0.001). These species of APP were soluble, lacked the carboxyl terminus, and the 110- and 42-kd species were shown to be consistent with degradation products derived from the 130-kd species. A comparison of levels of 130-kd plasma APP from moderately to severely demented patients with AD and control subjects distinguished the two groups with a specificity of 87.0% and a sensitivity of 79.4%. PMID- 1642474 TI - L-2-hydroxyglutaric acidemia: a novel inherited neurometabolic disease. AB - Routine screening for organic acids revealed increased and isolated urinary excretion of L-2-hydroxyglutaric acid in 8 mentally retarded patients from five unrelated families, including three pairs of siblings. L-2-Hydroxyglutaric acid concentration was also found to be increased in the cerebrospinal fluid (CSF) and to a lesser extent in plasma. The only other biochemical abnormality was an increased concentration of lysine, both in plasma and in CSF. No organic acid abnormality was found on screening of asymptomatic family members. Patients were of either sex, and became symptomatic during childhood, with moderate to severe mental deficiency in all and definite cerebellar dysfunction in 7. Magnetic resonance imaging revealed an identical abnormal pattern with subcortical leukoencephalopathy, cerebellar atrophy, and signal changes in the putamina and dentate nuclei, in all patients. No specific biochemical function or catabolic pathway involving L-2-hydroxyglutaric acid is known in mammals, including humans. Preliminary loading and dietary studies failed to reveal the origin of the compound. The elevated CSF/plasma ratio suggests that it is in part generated within the central nervous system. This report describes a novel inherited neurometabolic disease, probably autosomal recessive, with distinct clinical, biochemical, and neuroimaging features. PMID- 1642476 TI - Neurology research: a journal survey, 1980-1990. AB - There have been major changes in neurology research during the past decade, but no systematic examination of the content, methods, funding, and research personnel. All scientific articles in the journals Annals of Neurology, Archives of Neurology, and Neurology were categorized by article type, number of authors, highest degree of first author, institution, disease area, research field, and source of support for the years 1980 and 1990. Original articles grew by 54% over the decade. The average number of authors increased by 1.3 to 5 (p greater than 0.0001). Groups of MDs and PhDs wrote 39% of articles in 1990 (24% in 1980). Contributions with a diagnostic or therapeutic focus rose from 7 to 14%, whereas there was a pronounced drop in case reports from nearly 40% to just under 20%. Articles on movement disorders and neurodegenerative diseases increased more than 100% and now together comprise more than 25% of original articles. Molecular biology increased by 1,600%, and there was significant growth in epidemiology, neuro-imaging, neurochemistry, and neuropsychology. The top 20 publishing institutions accounted for 40% of all original articles and 60% of US original articles. Foreign contributions doubled over the decade. The National Institutes of Health funded 46% of US articles in 1990 (35.5% in 1980). More than 80% of articles in 1990 on neurodegenerative disease were supported by the National Institutes of Health. The complexity of neurological research has driven greater collaboration between basic and clinical scientists. New areas of clinical and basic knowledge are rapidly emerging in neurology. PMID- 1642475 TI - Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. AB - An open angiography-based, dose rate escalation study on the effect of intravenous infusion of recombinant tissue plasminogen activator (rt-PA) on cerebral arterial recanalization in patients with acute focal cerebral ischemia was performed at 16 centers. Arterial occlusions consistent with acute ischemia in the carotid or vertebrobasilar territory in the absence of detectable intracerebral hemorrhage were prerequisites for treatment. After the 60-minute rt PA infusion, arterial perfusion was assessed by repeat angiography and computed tomography scans were performed at 24 hours to assess hemorrhagic transformation. Of 139 patients with symptoms of focal ischemia, 80.6% (112) had complete occlusion of the primary vessel at a mean of 5.4 +/- 1.7 hours after symptom onset. No dose rate response of cerebral arterial recanalization was observed in 93 patients who completed the rt-PA infusion. Middle cerebral artery division (M2) and branch (M3) occlusions were more likely to undergo recanalization by 60 minutes than were internal carotid artery occlusions. Hemorrhagic infarction occurred in 20.2% and parenchymatous hematoma in 10.6% of patients over all dose rates, while neurological worsening accompanied hemorrhagic transformation (hemorrhagic infarction and parenchymatous hematoma) in 9.6% of patients. All findings were within prospective safety guidelines. No dose rate correlation with hemorrhagic infarction, parenchymatous hematoma, or both was seen. Hemorrhagic transformation occurred significantly more frequently in patients receiving treatment at least 6 hours after symptom onset. No relationship between hemorrhagic transformation and recanalization was observed. This study indicates that site of occlusion, time to recanalization, and time to treatment are important variables in acute stroke intervention with this agent. PMID- 1642477 TI - Plasma exchange in Guillain-Barre syndrome: one-year follow-up. French Cooperative Group on Plasma Exchange in Guillain-Barre Syndrome. AB - We report the one-year assessment of plasma exchange (PE) versus control in Guillain-Barre syndrome (GBS), based on a randomized multicenter clinical trial of 220 patients with GBS. Treated patients received four PEs, with either albumin or fresh frozen plasma (FFP) as replacement fluid. This study completes the short term analysis previously published (Ann Neurol 1987;22: 753-761). Long-term benefit from PE was observed, as demonstrated by full muscular strength recovery at one year: 71% in the PE group versus 52% in the control group (p = 0.007), confirmed after adjustment for four prognostic factors. FFP showed no additional benefit compared with albumin (77% full recovery in the FFP group versus 65% in the albumin group; p = 0.22). PE did not affect the incidence of severe motor disability (11% in both groups). PMID- 1642478 TI - Lack of major olfactory dysfunction in MPTP-induced parkinsonism. AB - The olfactory function of 6 patients whose parkinsonism was the result of intravenous administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was compared to that of 12 age-matched patients with idiopathic Parkinson's disease (PD) and 10 age-matched normal control subjects. Unlike their PD counterparts, the olfactory test scores of patients with MPTP-induced parkinsonism did not differ significantly from those of control subjects. These findings suggest that MPTP-induced parkinsonism, unlike idiopathic PD, is unaccompanied, on average, by major alterations in the ability to smell. PMID- 1642479 TI - Recent advances in the design of HIV proteinase inhibitors. AB - Inhibition of HIV proteinase is currently one of the most widely studied approaches for chemotherapeutic intervention in the treatment of AIDS. A range of inhibitors of this essential enzyme has been designed from detailed knowledge of its mechanism of action and cleavage sites. These inhibitors have been classified according to their derivation. All are transition-state analogues and contain a hydroxyethylene, hydroxyethylamine, phosphinate or symmetrical moiety. Many of these inhibitors have high selectivity for the viral enzyme and significant antiviral activity. Advances in the design of HIV proteinase inhibitors that have been reported in the past year are reviewed. PMID- 1642480 TI - Antisense inhibitors of HIV: problems and perspectives. PMID- 1642481 TI - Challenges in the clinical development of antiretroviral drugs. PMID- 1642482 TI - Aryl phosphate derivatives of AZT retain activity against HIV1 in cell lines which are resistant to the action of AZT. AB - Novel aryl phosphate derivatives of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. These materials are designed to act as membrane-soluble pro-drugs of the bio-active free nucleotides. In vitro evaluation revealed the compounds to have a pronounced, selective antiviral activity, which, in one case, was more potent than the parent nucleoside AZT. The magnitude of the biological effect varied considerably with the nature of the phosphate-blocking group. Moreover, one of the compounds, a phosphoramidate, is particularly active in a cell line restrictive to the activity of AZT, due to poor phosphorylation therein. These data support the suggestion that the phosphate derivatives exert their biological effects via intracellular release of the nucleotide forms. PMID- 1642483 TI - Clinical assessment of confusion in long-term care. PMID- 1642484 TI - A researcher as resource, mentor, and preceptor. PMID- 1642485 TI - How to behave at a research meeting. PMID- 1642486 TI - Predictors of general activity 8 weeks after cardiac surgery. AB - In this secondary analysis, the influence of mood states and self-efficacy beliefs on recovery of general activities 8 weeks after cardiac surgery were investigated. Study data were taken from a randomized clinical trial with 156 subjects who were either in an efficacy enhancement nursing care group (n = 75) or in a routine care group (n = 81). It was found that self-efficacy beliefs at time of hospitalization regarding ability to resume general activities after discharge, measured tension/anxiety at 4 weeks after surgery, and experimental group status explained 21% of the variation in self-reported recovery at 8 weeks. PMID- 1642487 TI - Comparing two models of discharge planning rounds in acute care. AB - Rounds are a primary part of the discharge planning process in acute care hospitals. The multidisciplinary aspect of rounds has been accepted as a given, but the differences resulting from differently composed interdisciplinary groups functioning in rounds has not been investigated. This experimental study examined two models of discharge planning rounds and compared their effects on the process of probing, identifying, planning for, and following through on patient discharge needs. PMID- 1642488 TI - Uninsured maternity clients: a concern for quality. AB - Differences among demographic characteristics, health status indicators, and resource use of maternity clients privately insured, insured through public entitlement funds, or uninsured were examined in a public hospital. The uninsured were in their early twenties, black (44%), single (52%), lived in the central city area, employed in service occupations without health care benefits, and either sought prenatal care later in the pregnancy or not at all. Compared with the privately insured, the uninsured had more lifestyle risks. The uninsured women had a shorter hospital stay with more maternal complications. Insurance coverage and prenatal care were positive predictors of birth weight and lifestyle risk factors detracted. Length of stay was not influenced by insurance coverage but rather by health problems before delivery. Earlier discharge of the uninsured patients suggest the need for quality of care monitoring and outreach programs. PMID- 1642489 TI - Relationship between body image and chronic obstructive pulmonary disease. PMID- 1642490 TI - Effect of nitropaste administration times on sleep and nocturnal angina. PMID- 1642491 TI - Nurses' perceptions of reportable medication errors and factors that contribute to their occurrence. PMID- 1642492 TI - Motivation of subjects to participate in a research trial. PMID- 1642493 TI - Practice-based research in maternity nursing: issues and examples from studies of labor and birth. PMID- 1642494 TI - [How extensive can injury of the larynx in self-choking be?]. AB - Is it possible to distinguish between suicidal and homicidal strangulation by the extent of the injuries of the larynx if the results of the police investigations are uncertain? Therefore evaluation of the German publications (115 reported cases of suicidal strangulation) and our own cases (17 cases). Hereafter more intensive injuries of the neck are extremely rare in cases of self-strangulation. Casuistic: Body of a 40 years old woman with signs of strangulation. The husband declared his wife strangulated herself in the bathtub with the belt of a bathrobe. Autopsy: Typical findings of drowning, intensive injuries of the neck tissues and the larynx. Kind and extent of the findings are speaking well for an assault mainly by manual strangulation. Undepending of the medical findings the police investigations are almost excluding a suicide. Condemnation of the husband. PMID- 1642495 TI - [An unusual case of suicide caused by electric current]. AB - The authors describe a suicide case of a 37 year old master joiner caused by electricity. One wire was put around a neck and the other around the left wrist. PMID- 1642496 TI - [Unusual fatalities caused by glass splinter injury]. AB - In the case of a thorax stab wound and an intrapulmonal position of the glass fragment (fall from a ladder into a glass door) an extrathoracic cardiac massage had been carried out. The result of which, an extremely unusual "reanimationtrauma" and the problems connected with it are discussed. In another case of a stab wound of the right iliacal vessels and the position of the glass fragment in the minor pelvis (jump through a thermopane glass of a door, followed by a fight) investigations were first conducted because of the suspicion of manslaughter. The autopsy, however, completely excluded death through fault of another. Further an unusual figured glass cut wound on the left side of the head (fall into a glass brick wall) led to death through gradual bleeding. The question arose whether death was caused by failure to give assistance. PMID- 1642497 TI - [Separation of stomach contents using the sieve-tower technique]. AB - The authors present a method to separate and preserve stomach contents for forensic purpose. Analysis by "sieve tower" technique is simple and quickly done during autopsy. Solid phases of stomach content are arranged size up and can be stored for subsequent examinations. With the fluid phase drug analysis or microscopic analysis to confirm identy of the foodstuffs may be done. By adding alcohol (70%) enzymatic digestion and bacterial degradation of the stomach content are stopped. PMID- 1642499 TI - [Significance of tachycardia induced by atrial stimulation in Wolff-Parkinson White syndrome]. AB - Increased atrial vulnerability is one of the criteria of malignant Wolff Parkinson-White syndrome. The aim of this study was to try to define the methods of induction of atrial tachycardias (tachycardia, flutter, fibrillation) by endocavitary and oesophageal stimulation characterising an increased vulnerability. The incidence of induced sustained tachycardia by fixed atrial stimulation at incremental rates until the Wenckebach point is attained and programmed atrial stimulation using 1 and 2 extrastimuli under basal conditions and then with isoproterenol was compared in subjects without cardiac disease, Wolff-Parkinson-White or spontaneous tachycardia (Group I) and patients with Wolff-Parkinson-White and spontaneous tachycardias (Group II). Atrial stimulation only induced tachycardia in 2.5% of normal subjects under basal conditions or with isoproterenol, by the endocavitary or oesophageal approaches. Programmed stimulation induced tachycardia in 15% of normal subjects under basal conditions or with isoproterenol by the endocavitary approach alone. In Group II, tachycardia was reproduced under basal conditions or with isoproterenol by atrial stimulation or programmed stimulation in all patients. In conclusion, the induction of a tachyarrhythmia by incremental atrial stimulation up to the Wenckebach point is always pathological even with isoproterenol. Programmed atrial stimulation is less specific except by the oesophageal approach. The use of bursts of very rapid stimuli in the Wolff-Parkinson-White syndrome is of no value as tachycardia can be induced by classical methods in all subjects at risk. PMID- 1642498 TI - [Multi-locus DNA fingerprints using oligonucleotide probe (CAC)5/(GTG)5 in the Chinese population]. AB - In order to test the practical applicability of oligonucleotide fingerprinting in China we have investigated unrelated individuals, family members and a pair of twins from the Beijing area using the probe (CAC)5/(GTG)5. Except for the monozygotic twins highly variable banding patterns were demonstrated as expected for the randomly selected individuals but also for the relatives. On the basis of an initial survey of 50 unrelated individuals the calculated probability for obtaining by chance two identical multilocus patterns is very small (less than 1.93 x 10(-13). Therefore it seems reasonable to conclude that like in caucasians, (CAC)5/(GTG)5 fingerprints are completely individual-specific also in this population. Therefore they have already been used successfully for identification purposes and paternity tests in many actual cases. PMID- 1642500 TI - [Transesophageal echography and peripheral arterial embolism. A new etiologic approach. Apropos of 87 cases]. AB - This prospective study (September 1989 to November 1990) was undertaken to evaluate the utility of transesophageal echocardiography in acute peripheral ischaemic syndromes. After embolectomy or thrombolysis, 87 patients with an average age of 69.7 years underwent not only the usual investigations (conventional echocardiography, abdominal ultrasonography and Holter monitoring) but also transesophageal echocardiography within 2 days of the ischaemic events (lower limb 84%, multiple embolism 11%, recurrent embolism 13%). Atrial fibrillation was documented in 44 patients (50.5%), 19 patients had chronic arterial disease (22%), 8 patients had valvular heart disease (9%) and 2 patients had a blood disorder (2%). Transthoracic echocardiography only demonstrated one left ventricular apical thrombus whereas transesophageal echocardiography showed residual thrombus in 22 patients (25%) mainly in the left auricle but also in the descending thoracic aorta (8 patients) as a mobile, pediculated thrombus or lining an aortic aneurysm, thereby opening up new therapeutic possibilities. In addition, double aortic dissection was diagnosed in a patient who was not echogenic, isolated spontaneous contrast in 20 patients (23%) and other abnormalities in 7 patients (8%). Statistical analysis showed a significant relationship between the presence of thrombus and/or spontaneous contrast in the left atrium and/or left auricle and the size of the left atrium (Fisher test - p = 0.0073), and the presence of a supraventricular arrhythmia (chi 2 test). PMID- 1642501 TI - [Etiologic course of heart valve diseases surgically treated during 20 years in France]. AB - The aim of this study was to analyse the evolution of the aetiologies of operated valvular heart disease over a 20 year period and to assess the consequences. Two thousand five hundred and ninety eight patients who underwent conservative surgery or valve replacement were included. This population was classified according to the date of surgery into 4 groups, each corresponding to a 5 year period. Analysis of these results, especially in the groups operated between 1970 and 1974 and between 1985 and 1989 shows: 1) a change in aetiology: decreased incidence of rheumatic valvular disease (36 versus 61%) and an increased incidence of degenerative lesions (43 versus 23%) (p less than 0.0001); 2) a change in the valvular lesions operated, aortic stenosis has become the commonest operated condition (43 versus 27%) (less than 0.001); 3) an increased age (59 +/- 14 versus 49 +/- 13 years, p less than 0.0001) with a higher proportion of patients over 70 years of age (22 versus 1%, p less than 0.001); 4) a higher incidence of mixed coronary and valvular surgery (11 versus 2%, p less than 0.001). PMID- 1642502 TI - [Myocardial dissection in infarction of the right ventricle. Clinical echocardiographic and pathological aspects]. AB - Dissection of the inferior wall of the right ventricle during the acute phase of myocardial infarction with right ventricular involvement is a mechanical complication which has been recently identified, the diagnosis being almost exclusively post-mortem. The authors report the clinical, echocardiographic and pathological features of myocardial dissection in four patients. Between 1985 and 1988, the diagnosis of myocardial dissection was made by echocardiography in 4 patients aged 77 to 80 years, admitted to hospital for an acute inferior wall myocardial infarction. All 4 patients had signs of acute right ventricular failure indicating right ventricular necrosis and a loud systolic murmur at the left sternal border; 2 patients were in shock. The ECG showed signs of inferior wall infarction with, in 2 patients, electrical changes suggestive of right ventricular involvement. Echocardiography showed dissection of the inferior wall of the right ventricle as a pulsatile, echo-free space in the diaphragmatic wall of the right ventricle which appeared to obstruct right ventricular ejection in end systole to a variable degree. The outcome was fatal in all cases with death resulting from refractory myocardial failure. Pathological analysis confirmed biventricular inferior wall infarction also involving the posterior part of the interventricular system, the site of a small tear on the left side which communicated with a neo-cavity dissecting the RV posterior wall. The right coronary artery was totally occluded in all cases. The anatomical lesions were fully concordant with the echocardiographic data: the dissection filled with blood from the left ventricle at each systole creating a pulsatile space in the diaphragmatic wall of the ventricle obstructing ejection. PMID- 1642503 TI - [Technical problems during coronary revascularization in case of massive calcified aorta]. AB - A massively calcified ascending aorta which may make aortic clamping impossible, is a major obstacle to coronary revascularisation surgery. The aim of this study was to demonstrate that by the use of certain technical modifications, these patients can be treated even in multivessel disease. In the author's experience, two patients with this condition underwent complete revascularisation with a good surgical result controlled by angiography. The sites of arterial cannulation were the aortic arch in one case, the brachiocephalic artery and the common femoral artery in the other case. The ascending aorta was not clamped in either patient or used as the origin of the coronary bypass grafts. Myocardial protection was performed by systemic cooling with ventricular fibrillation without cardioplegia. The feasibility of these methods has led to the suggestion of a classification of the aortic wall according to peroperative palpation. This classification would provide indications for the use of technical modifications not only in extreme cases of aortic calcification but also in patients with severe atherosclerotic changes at high neurological risk; it would not, however, interfere with the classical technique of revascularisation. PMID- 1642504 TI - [Immediate and mid-term results of percutaneous pulmonary valvotomy in adults. Apropos of 10 cases]. AB - Percutaneous pulmonary valvulotomy (PPV) is the treatment of choice for isolated congenital pulmonary stenosis of infancy. However, experience with this technique in the adult is much more limited. From November 1983 to November 1990, PPV was performed in 10 adults in our Institute. The mean age was 40 +/- 19 years (range 21 to 71 years). Before PPV, 4 patients were in functional Class II and 6 in functional Class III of the NYHA classification. All procedures were successful with no complications. The right ventricular systolic pressure decreased from 98 +/- 35 to 57 +/- 30 mmHg (p less than 0.01) and the mean pulmonary gradient decreased from 57 +/- 30 to 23 +/- 15 mmHg (p less than 0.01). The cardiac output was unchanged: 5.3 +/- 2.8 and 5.9 +/- 2.6 l/mn (not significant). Pulmonary valve area increased from 0.59 +/- 0.3 to 1.15 +/- 0.5 cm2 (p less than 0.01). The post-dilatation infundibular gradient was less than 10 mmHg in all patients. After an mean follow-up period of 29 +/- 26 months all but one patient (Class II) were in functional Class I. Exercise capacity was 6.9 +/- 2 Mets. Doppler echocardiography indicated a stable mean pulmonary gradient of 16.5 +/- 6.8 mmHg after PPV and 15.0 +/- 7.0 mmHg during follow-up. Pulmonary regurgitation was less than Grade I in all cases. In conclusion, PPV is an effective treatment for adult pulmonary stenosis and carries a low risk. The mid term results are excellent. PMID- 1642505 TI - [Oxygen free radicals in cardiology]. AB - Oxygen free radicals are extremely toxic chemical entities derived from oxygen metabolism. This is a physiological process which explains a great deal of the phenomenon of phagocytosis. Under normal conditions, the body's natural defense mechanism neutralise the oxygen-free radicals as they are produced. In certain pathological situations, a disequilibrium is observed between the free radical aggression and the defense systems which creates an oxidative stress and organ damage. In cardiology, the oxidative stress occurs essentially in the phenomenon of reperfusion ischaemia. It is partially responsible for the reperfusion arrhythmias and myocardial stunning. An irreversible myocardial disease such as myocardial infarction, the responsibility of the oxidative stress is more uncertain. In myocardial protection during cardiac surgery the radical-induced damage occurs without it being possible to demonstrate the phenomenon in irreversible myocardial disease. The role of oxidative stress is unquestionable in myocardial reperfusion ischaemia. The detection of sensitive biological markers and a better understanding of the physiopathology should increase our knowledge of oxygen free radicals and enable effective treatment of their complications. PMID- 1642506 TI - [Should inferior myocardial infarction be thrombolysed?]. AB - Recent randomised studies have demonstrated the benefits of administration of intravenous thrombolytic agents in the acute phase of myocardial infarction. Though the benefits are generally acknowledged in cases of anterior wall necrosis, the results in inferior infarction have been discordant. The early patency rate at 90 minutes after thrombolysis is lower in the right coronary and left circumflex than in the left anterior descending artery. The secondary reocclusion rate is twice as high on the right coronary artery. The significant increase in ejection fraction after thrombolysis has only been demonstrated in 2 of the 8 studies in the literature. The benefits in terms of early mortality were not significant in the GISSI study. A significant decrease in early mortality (7.2% vs 8.8%) was observed only in the ISIS 2 study with streptokinase. The reinfarction rate at 1 year was twice as high when the initial infarct was on the inferior wall. Analysis of the results in the literature shows that the benefits of intravenous thrombolysis was clearcut in certain subgroups of inferior infarction: ST elevation in over 3 leads, mirror-image anterior lead changes, very early treatment (before the 3rd hour), complicated infarcts (atrioventricular block, right ventricular extension, hypotension) or in inferior infarcts occurring after previous anterior infarction. PMID- 1642507 TI - [Angiosarcoma of the aorta disclosed by intestinal metastasis]. AB - The authors report a case of angiosarcoma of the descending thoracic aorta presenting with a metastasis of the small intestine. This is a very rare tumour in this localisation, two cases having been described among the 28 cases of aortic tumour reported in the literature. PMID- 1642508 TI - [Left coronaro-ventricular fistula after septal myectomy]. AB - The authors report the case of a 17 year old patient operated for valvular aortic stenosis associated with severe hypertrophy of the interventricular septum. The operation consisted of aortic valve replacement and septal myectomy. Color-flow imaging in the postoperative period showed a coronary artery--left ventricular fistula in the region of the septal myectomy. In view of the small size of the fistula on echocardiographic examination and the absence of a codified strategy of management of acquired coronary left ventricular fistula after surgery, a simple Doppler echocardiographic follow-up was proposed in this case. PMID- 1642509 TI - [An unusual pericardial tumor: bronchogenic cyst]. AB - The authors report the case of an intrapericardial bronchogenic cyst in a 42 year old woman with no cardiac symptoms. Despite extensive investigation, the final diagnosis was made only at anatomopathological examination. A pericardial localisation of this embryological tumour is very rare and a number of features of the condition are described. In this case, the carbohydrate antigen (CA 19-9) was a veritable marker of this tumour. This association, described for the first time, between a simple biological marker and an intrapericardial bronchogenic cyst, could be a valuable diagnostic aid in a pathology in which surgery could reasonably be deferred should the diagnosis of bronchogenic cyst be certain. PMID- 1642510 TI - [Function and pharmacology of potassium channels in heart and vessels]. AB - The variability of the potassium channels in the cardiac tissues is remarkable. There are two main classes: voltage-operated channels and ligand-operated channels. The voltage-operated channels play a dominant role in the genesis of the resting potential (iK1) and the different phases of the action potential, the transient current ito during the initial phase of repolarisation, the iKp current and the slow current iK during the plateau phase. This class also includes the acetylcholine activated channel, iK(Ach). The ligand-operated channels seem to play a role in pathological situations such as ischaemia and anoxia: these channels are activated by a reduction in intracellular ATP or an increase in intracellular fatty acids or Na+. Substances blocking the iK and ito potassium channels have an anti-ischaemic effect. The agonists of ATP channels have a great therapeutic potential in vascular pathology, especially in the treatment of hypertension. PMID- 1642511 TI - [Structure and family of proteins, a puzzle]. AB - It now seems quite clear that the number of modes of three-dimensional arrangement of peptide chains of globular proteins is much smaller than the great sequential variability would suggest. Structural families and super families are formed with members which show little if any sequential identity (in the statistical sense) with older members of these families. In addition, it is evident that many proteins are formed like puzzles, by the juxtaposition of domains and sub-domains. Each brick usually has a well-defined intrinsic biological function. The components of these macro molecular puzzles have very different sizes, from a few amino acids to complete protein globules of several hundreds of amino acids, via intermediary local secondary ans super-secondary structures. This building system, the result of a long evolution after duplication or replication of genes, offers banks (sequences and three dimensional structures) while limiting the complexity of the protein world. PMID- 1642512 TI - [Charles Dubost. 1914-1991]. PMID- 1642513 TI - Activated species of oxygen: a challenge to modern pharmaceutical chemistry. PMID- 1642514 TI - [Cardenolide glycosides in Digitalis crossbreeds. Reciprocal crossbreeds of Digitalis lanata with other Digitalis species]. PMID- 1642515 TI - Synthesis and antihypertensive properties of some dopamino-pyridazin-3(2H)-one derivatives. PMID- 1642516 TI - Bimanual skill development in pediatric below-elbow amputation: a multicenter, cross-sectional study. AB - The purpose of this study was to investigate the following in children with unilateral below-elbow amputation: (1) development of bimanual functional skills, (2) development patterns relative to able-bodied children, and (3) the relationship between duration of prosthetic wear and bimanual functional performance. Sixty-nine children with unilateral below-elbow amputation, all less than ten years old, were assessed on 14 prosthesis-assisted bimanual ADL, including play, feeding, dressing, and hygiene activities, which have been studied previously in able-bodied children. Bimanual ADL skill development was not delayed in five of the 14 comparisons to previously published standards, but most development patterns had multimodal, nonmonotonic performance profiles. Duration of prosthetic wear and other factors previously believed to contribute to good prosthetic function were not well correlated to ADL skills (r less than .52). Although these children had no CNS dysfunction, it is apparent that below elbow amputation impedes pediatric ADL skill development. The cause of these delays appears to be complex and is not expressed uniformly among all children; thus, the delays observed are not simply due to mechanical deficiencies of the prosthetic restoration. PMID- 1642517 TI - The team approach to treatment of the dizzy patient. AB - This report describes how a rehabilitation team treats dizziness and vestibular disorders. Team members include a nurse, physician, audiologist, physical therapist, occupational therapist, and a research scientist. Although unusual, this multidisciplinary approach, involving a close-knit group of professionals, is of great benefit in the treatment of vestibular and balance disorders. PMID- 1642518 TI - Muscular endurance and wheelchair propulsion in children with cerebral palsy or myelomeningocele. AB - Bivariate correlations between muscular endurance or resistance used during six repetition maximum (6-RM) for eight upper body exercises (shoulder flexion, extension, abduction, internal and external rotation, elbow flexion, extension and shoulder flexion/elbow extension (bench press), 50-meter dash, and 12-minute wheelchair propulsion tests were examined in six children with diagnoses of cerebral palsy or myelomeningocele. Correlations were determined before and after resistance training. Before training, only elbow extension correlated significantly with the 12-minute test. Following training, significant correlations (p less than or equal to 0.05) were found between all 6-RM exercises and 12-minute test scores. Additionally, significant correlations were found between all 6-RM exercises (except elbow flexion, which approached significance) and 50-meter dash scores. The results of this clinical case investigation indicate that the relationship between muscular endurance (6-RM) and wheelchair propulsion improves as muscular endurance increases. PMID- 1642519 TI - Venous thromboembolism in patients undergoing rehabilitation for stroke. AB - OBJECTIVE: To determine the incidence of venous thromboembolism during rehabilitation for stroke and to identify factors that alter its risk. DESIGN: Cohort. SETTING: Tertiary care stroke rehabilitation program. PATIENTS: 102 consecutive patients undergoing rehabilitation for stroke. INTERVENTIONS: Impedance plethysmography (IPG) as routine screening and in patients with symptoms of deep venous thrombosis (DVT). MAIN OUTCOME MEASURES: DVT, pulmonary embolism (PE), death from PE. RESULTS: Venous thromboembolism was documented in 11 patients (11%) an average of 60 days after stroke onset (range 14-138 days); 2 patients (2%) died from PE. DVT was found on routine IPG screening in six patients and verified by IPG in two clinically symptomatic patients. The odds of developing venous thromboembolism was 17.6 (95% confidence interval: 2.2-143.5) in patients who were bedridden or wheelchair-bound at the time of admission. CONCLUSIONS: The incidence of venous thromboembolism is high and greatest in bedridden or wheelchair-bound patients undergoing stroke rehabilitation; randomized trials evaluating the safety and efficacy of screening and/or prophylaxis in such patients are required. PMID- 1642520 TI - Deep diaphragmatic breathing: rehabilitation exercises for the asthmatic patient. AB - A new diaphragmatic breathing technique practiced without the aid of a physical corset is outlined, and the findings from a study of its application in the respiratory rehabilitation of asthmatic patients are presented. Sixty-seven asthmatic adults randomly assigned to either deep diaphragmatic breathing training, physical exercise training, or a waiting list control group participated in a 16-week program. Deep diaphragmatic training resulted in significant reductions in medication use and in the intensity of asthmatic symptoms. Importantly, a nearly 300% increase in time spent in physical activities also resulted from deep diaphragmatic training. A follow-up at two months found many patients had returned to earlier medication levels and sedentary habits. A strengthened musculature can replace the need for a physical aid in this respiratory habilitation; adherence to its use may require individually-tailored encouragement. PMID- 1642521 TI - Nature, reliability, and predictive value of muscle performance measures in patients with hemiparesis following stroke. AB - The purposes of this investigation were to examine among a sample of hemiparetic stroke patients the nature and reliability of selected muscle performance measures and the correlation between the measures and gait speed. Fourteen subjects who met specific entry criteria participated. The Lido Active Rehabilitation System was used to obtain bilaterally all muscle performance measures of knee extension (velocity, isometric torque-peak and time specific, and time to peak torque and 90% peak torque). Gait speed was measured under both "comfortable" and "maximum safe" conditions. In addition to lower torques, the subjects demonstrated slower knee extension speeds and longer times to peak torque and 90% peak torque on the paretic than on the nonparetic side. High intrasession reliabilities were demonstrated for all muscle performance measures except the torque at 0.1 sec on the nonparetic side and the time to peak torque and 90% peak torque measures. Significant correlations were demonstrated between both gait speeds and paretic knee extension torque (except at 0.1 sec), nonparetic knee extension torque at 0.1 sec and 0.2 sec, and time to nonparetic peak torque. Muscle performance measures other than peak torque appeared to offer little advantage (alone) over paretic peak torque for predicting gait speed. Over 74% of the variance in gait speed, however, could be predicted by the peak isometric peak torque of the paretic side and the time to peak torque on the nonparetic side, together. Thus, there may be benefits to testing the muscle performance of both lower extremities when examining patients with stroke. PMID- 1642522 TI - Assessment of aerobic power in chronic pain patients before and after a multi disciplinary treatment program. AB - Physical exercise is widely used in the treatment of chronic pain patients, and direct measurement of physical capabilities is needed to objectively document change. In this study, 46 residential chronic pain patients undergoing treatment at a multidisciplinary rehabilitation center were administered a cycle ergometer graded exercise test, using a Medical Graphics CAD/NET exercise system, to measure aerobic fitness and other physiological parameters before and after the four-week treatment program. Patients evinced highly statistically significant changes in all major indices of cardiopulmonary functioning, including MAXVO2 and METS, and a measure of lower body power (WATTS). Possible mechanisms underlying such dramatic changes in this short time period include improved physical fitness, learning or desensitization to symptoms associated with exertion, and improved effort. Documenting treatment-related changes is important, and metabolic exercise testing provides an objective method for assessing changes in functional capacities. Such changes may have important practical implications for these individuals. The importance of assessing and improving aerobic fitness in chronic pain populations is discussed. PMID- 1642524 TI - Cervical rotation lateral flexion test in brachialgia. AB - The cervical rotation lateral flexion test (CRLF test), developed earlier, was used to examine patients with brachialgia and thoracic outlet syndrome (TOS) symptoms to detect possible restriction of the movement of the first rib. The test was performed for 23 patients, five of them both before and after treatment. The patients were assessed independently by two clinicians to analyze the interobserver reliability. A cineradiographic examination was performed so that any restriction of the movement of the first rib during expiration and inspiration could be detected objectively. The interobserver repeatability of the test was excellent, thus making the cineradiographic examination unnecessary. It is recommended that this test be included in the clinical investigation of all patients with brachialgia with or without radicular pain. PMID- 1642523 TI - Silent ischemia in rehabilitation patients: limited clinical utility of electrocardiographic monitoring. AB - In a prospective blinded trial, 24-hour continuous electrocardiographic monitoring for silent ischemia was used to try to identify rehabilitation patients at risk for cardiac complications. Five of 42 patients had episodes of silent ischemia, none of which occurred during physical therapy sessions. One of these patients had syncope while wearing the Holter; none of the other four patients had significant cardiac complications during their rehabilitation, and all were discharged home. None of the patients without ischemia on the monitor had complications, but two patients of 14 whose ECGs precluded monitoring for ischemia had complications. In addition, six patients had episodes of nonsustained asymptomatic ventricular tachycardia, 12 had episodes of supraventricular tachycardia, and four had significant ventricular ectopy, all without clinical significance. Despite the apparent high sensitivity and specificity of the technique, the positive predictive value of monitoring eligible patients for silent ischemia was 20%. We conclude that ambulatory electrocardiographic monitoring for silent ischemia or ectopy has limited clinical utility in the rehabilitation population. PMID- 1642525 TI - Training effects during repeated therapy sessions of balance training using visual feedback. AB - Visual biofeedback of postural sway is currently being investigated as a therapeutic technique to reduce postural instability in selected patient populations. Before the efficacy of this type of therapy can be determined in a clinical setting, the performance curves of a normal population doing the static and dynamic balance training exercises have to be delineated. Two groups of normal subjects were evaluated during a daily and weekly protocol of dynamic balance exercises using visual feedback of their center of gravity (COG) and theoretical limits of stability. Static stability in a central position was measured with eyes open, eyes closed, and with visual feedback of the COG in a pre-therapy to post-therapy assessment. No significant change was observed in any of these variables from the pre-therapy to the post-therapy evaluation; as well there was no difference between the scores of both groups. Dynamic variables were evaluated in both a pre-therapy to post-therapy assessment, and over the course of therapy. Each of these protocols required the subjects to track targets representing 75% of their limits of stability on a computer screen with their COG. The time taken and the accuracy to move the COG cursor from target to target, as well as the body sway upon reaching the target were evaluated. Transition time and sway area both decreased significantly (p less than 0.01) from the pre-therapy to the post-therapy assessment for both groups, with path error decreasing significantly for the daily therapy group only. No significant difference was demonstrated between groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642526 TI - Spinal mobility and muscular strength: effects of supine- and prone-lying back extension exercise training. AB - This study compared the effectiveness of supine-lying back extension (SBE) exercise and prone-lying back extension (PBE) exercise on spinal mobility and muscular strength. A 3 (groups) x 4 (time frames) experimental design was used. Thirty-four healthy men (mean age, 23.1 +/- 2.1 years) were randomly assigned to three groups. Subjects in group 1 (n = 11) were trained using the SBE protocol, whereas those assigned to group 2 (n = 12) performed the PBE program. Subjects in group 3 (n = 11) received no exercise training and served as controls. The exercise programs were standardized and administered three times a week for 6 weeks. The spinal range of motion (ROM) and back extension isometric force of all the subjects was evaluated before training, at the end of the third and sixth weeks of the study, and 9 weeks after the end of the exercise training. A two factor (group and time frame), repeated-measures ANOVA was used to determine significant differences in spinal ROM and back extension isometric force among the groups at the different time frames. The results of the statistical analyses showed progressive increases (p less than .05) in spinal ROM and isometric force after the exercise training; they had increased by 12.6% and 19.2%, respectively, at the end of the sixth week of training. The gain in spinal mobility was completely obliterated nine weeks posttraining. However, the improvement in muscular strength was sustained 9 weeks after the end of physical training. The SBE method was better for improving the spinal ROM, whereas the PBE method was more effective in augmenting muscular strength of the back. PMID- 1642527 TI - Hospitalizations for hip fractures among elderly persons in Hawaii, 1986-1990. AB - Hawaii differs ethnically, geographically, and culturally from other states; therefore, United States hip fracture data cannot be assumed to apply to Hawaii. The purpose of this research was to gain new knowledge about hip fracture in Hawaii to plan and target appropriate services and design preventive measures. Peer Review Organization Medicare data were analyzed for persons age 65+ over a 4 year period. Average length of hospital stay was 20 days resulting in an average estimated charge per hospitalization of $20,000. Of those with E-Codes, 94% sustained falls. Fifty-five percent had one or more complicating illness. Unexpected significant differences were found among the islands: the average annual hospitalization incidence rate/1,000 on Kauai (8.4) was almost twice that of the Island of Hawaii (4.4), and Maui (3.9), and significantly greater than Oahu (5.4), primarily in women over 85. The island differences raise important questions in need of investigation, and suggest target populations and locations for prevention. PMID- 1642528 TI - Recovery from diffuse traumatic brain injury in Johannesburg: a concurrent prospective study. AB - Three hundred and twenty-six persons with light, moderate, or severe diffuse traumatic brain injury (TBI) were assessed during initial hospitalization in Johannesburg. One hundred and forty-four were followed up at approximately six months, 83 at 12 months, and 71 at 24 months posttrauma. The sample attrition rate was high. When patients could not be found, data were obtained from their caregivers. Recovery was measured in five different areas of functioning: family relationships, psychologic problems, activities of daily living (ADL), employment status, and physical status. Psychologic problems and family relationships worsened with time, but proficiency in ADL improved; physical and employment status remained relatively stable during the survey period. Severity of injury was significantly correlated with outcome in each functional area at some point in the follow-up period. Discrepancies between patients' and caregivers' perceptions of outcome were noted, particularly in the area of psychologic functioning. Caregivers tended to rate the recovery made by the patient as better than the outcome patients perceived themselves to have made. These differences in perception diminished with time. The multifactorial nature of recovery after TBI is indicated by the improvements seen in some functional areas and the worsening of outcome in other areas. These findings suggest that rehabilitation programs for persons with TBI should (1) include caregivers, (2) focus on the adjustment of both parties to their new circumstances, and (3) facilitate a convergence in their perceptions. Adequately defining recovery is a first step to estimating the prevalence of TBI, but necessitates further work. Epidemiology awaits a better understanding of the recovery process after TBI. PMID- 1642529 TI - Traumatic brain injury: family response and outcome. AB - Family outcome following traumatic brain injury has been the subject of investigation for nearly two decades. Researchers have reported on samples from Israel, Scotland, Denmark, England, and the United States. Cultural diversity as well as differences in design, assessment methods, injury characteristics, and definitions have contributed to difficulties establishing definitive conclusions. Findings indicate that patients' levels of emotional and personality disturbances are associated with levels of family disturbance, and are relatively more significant than physical disability. Undeniably, the long-term sequelae of injury have a long-term negative impact on families. Unfortunately, little has been done to establish the nature of family outcomes for patients younger than age 17, siblings, and less than severe injuries. Recent advances including development of valid measurement tools, definitions established through consensus, and multi-center collaborative research networks are promising and contribute to the likelihood of imminent progress. PMID- 1642530 TI - Independent insulin administration by the hemiplegic patient: stabilization of an insulin pen with a new device. AB - Diabetes mellitus is an independent risk factor for stroke, and the incidence of diabetes in patients presenting with stroke is 16% to 20%. Administration of insulin is an important activity of daily living that should be addressed in hemiplegic patients with diabetes. Presented here is a table-top clamp that can be used with an insulin pen allowing independent insulin dosing and subcutaneous administration with one hand. The clamp is built on a wood block base that is mounted to a smooth table surface by suction cups. Construction of the device is simple, inexpensive, and can be incorporated as a therapeutic project for the patient during the rehabilitation stay. A diabetic patient with a left hemiplegia is presented who demonstrated independence with the device prior to her discharge home. PMID- 1642531 TI - Diagnosis of myocardial contusion. Quantitative analysis of single photon emission computed tomographic scans. AB - Prior studies from our institution have shown that single photon emission computed tomography is sensitive (100%) in predicting patients at risk for serious arrhythmias. However, the positive predictive value is low (15% to 20%). The purpose of this study was to determine if quantitative analysis of single photon emission computed tomographic defects could improve predictive value. One hundred seventy-five patients with positive single photon emission computed tomographic scans were studied. One hundred two patients developed arrhythmias, 42 of which were ventricular. Arrhythmias were associated with all defect loci and all defect sizes. The incidence of arrhythmias did increase with increasing size. Patients were at risk for arrhythmias up to 72 hours after trauma. The value of single photon emission computed tomography is its ability to predict patients at risk for arrhythmias. This study shows that any single photon emission computed tomographic defect, regardless of location or size, is a significant predictor of arrhythmias. PMID- 1642532 TI - Postinjury shock and early bacteremia. A lethal combination. AB - Gut bacteria translocation has been invoked as a prime cause of early postinjury death. To examine this hypothesis, we obtained emergency department blood cultures in 132 acutely injured patients requiring urgent laparotomy for trauma. In the latter half of these patients, mesenteric lymph node and liver biopsy cultures were also performed. The incidence of early bacteremia was 11% (10/94) in the patients without shock compared with 32% (12/38) in the group with shock. The majority (73%) were gram-positive bacteremias. Most notably, Staphylococcus was isolated in 13% (5/38) of the patients with shock, but these isolates were of no apparent clinical significance. In contrast, 18% (7/38) of the patients with shock had enteric bacteremias, and all of these patients died. Cultures were positive in 11% of the liver samples and 15% of the mesenteric lymph nodes. With the exception of two patients with concurrent enteric bacteremias, these hepatic and mesenteric lymph node bacteria were of no clinical significance. In conclusion, bacterial translocation occurs infrequently, and virtually all enteric bacteria were found in dying patients; the cause or effect remains to be defined. PMID- 1642533 TI - The catecholamine response to multisystem trauma. AB - We studied the catecholamine response in two groups of patients with multisystem injuries according to the presence (group 1, N = 124) or absence (group 2, N = 82) of head injury. Markers of injury severity included the injury Severity Score, the Glasgow Coma Scale, the need for intubation, admission hypotension, the amount of blood products and fluid expanders administered during the first 24 hours, and patient outcome. In group 1, higher norepinephrine levels always and epinephrine concentrations usually were associated with worsening indexes of injury severity. The best correlations were between the Injury Severity Score and the Glasgow Coma Scale and norepinephrine concentrations. In group 2, despite elevated catecholamine levels, such associations were seldom present. Thus, circulating catecholamine levels, especially norepinephrine levels, significantly correlated with the severity of injury in patients who had suffered multisystem injury, but only if the injury included the brain. PMID- 1642534 TI - The continuing dilemma of lobular carcinoma in situ. AB - We reviewed the courses of 250 consecutive women with lobular carcinoma in situ of the breast entered into the Surveillance, Epidemiology, and End Results program of the Michigan Cancer Foundation, Detroit, Mich, between 1973 and 1986. No patient had known invasive cancer at the time of initial entry. The average follow-up was 93.1 months; 212 patients had mastectomy for the initial lesion and 65 patients had less than mastectomy, of whom one developed a new lesion in the ipsilateral breast. Thirty-seven patients (14.8%) were later found to have lesions in the contralateral breast, 25 within the first year. Thirteen of the 38 lesions (5.2% of the total series) were invasive, and 11 were primarily ductal. Seventeen patients died, two of breast cancer, two of unknown causes, and 13 of non-breast-related causes. The maximum mortality from breast cancer is 1.6% to this point. The frequency of mastectomy fell from 78.1% in the years 1973 through 1983 to 52% in 1984 through 1986, reflecting a change in surgical philosophy. Although no guarantees can be given to any individual patient, the great majority of patients with LCIS unassociated with a proved invasive cancer can be safely treated with less than mastectomy. PMID- 1642535 TI - Primary tumor size. Relevance to breast cancer survival. AB - In view of current emphasis on identifying prognostic factors for patients with early breast cancer, we studied the importance of tumor size to survival among 1392 patients with primary operable breast cancer who were followed up prospectively. All patients had modified radical mastectomies. Nine hundred seventeen patients had negative nodes and did not receive postoperative adjuvant therapy. Four hundred seventy-five patients had node involvement and received combination chemoendocrine therapy. In a Cox's proportional hazards model, tumor size was a significant predictor of disease-free and overall survival when the number of positive nodes, estrogen receptor status, menopausal status, and race were considered. Among the node-negative group, tumor size explained considerable variation in disease-free and overall survival, varying from a 10-year disease free and overall survival of 80% and 99% for patients with estrogen receptor positive tumors measuring 1 cm or less to a 10-year disease-free and overall survival of 51% and 59% for patients with tumors larger than 5 cm. PMID- 1642536 TI - Hirschsprung's disease. Evaluation of mortality and long-term function in 260 cases. AB - This report describes 260 patients treated for Hirschsprung's disease. There were 213 boys (82%) and 47 girls (18%). Age at diagnosis was younger than 30 days in 106 patients (41%), 1 month to 1 year in 90 patients (35%), and older than 1 year in 64 patients (25%). Diagnosis was achieved with barium enema and rectal biopsy. Aganglionosis involved the rectum or rectosigmoid in 174 patients (67%), the left colon in 38 patients (15%), and the proximal colon in 23 patients (9%); 25 patients (9%) had total colonic aganglionosis. Enterocolitis occurred in 47 cases (18%). Following an initial colostomy or ileostomy, a definitive pull-through procedure was performed in 247 patients (95%) (modified Duhamel in 185, Soave in 25, Swenson procedure in 15, and anomyectomy/sphincterotomy in 22); the overall survival rate was 93.8% (244 of 260 patients). An increased mortality was associated with Down syndrome, total colonic aganglionosis, and enterocolitis. Long-term follow-up (mean, 6 years 10 months) was available in 103 patients who underwent a Duhamel procedure. Sixty-seven (65%) had normal bowel function, 28 (27%) occasionally used enemas or stool softeners, and eight (8%) had severe constipation or soiling. Bowel habits improved with time and were considered normal in 58% of patients at less than 5 years of follow-up and in 88% of patients at more than 15 years of follow-up. The Duhamel operation is a very effective definitive procedure for Hirschsprung's disease. Long-term follow-up is an important component of patient care. PMID- 1642537 TI - Transhiatal and transthoracic esophagectomy for adenocarcinoma of the esophagus. AB - Adenocarcinoma of the esophagus is no longer rare and is treated by resection. To determine whether the approach used for resection influences outcome, we studied 88 patients who underwent resection; 14 had stage I or II disease, 74 had stage III, and 40 had stage IV. One third of those with Barrett's esophagus were noted on screening endoscopy to have potentially curable disease; the others were diagnosed with stage III or IV disease. Transhiatal esophagectomy was performed in 63 patients; 24 patients underwent transthoracic esophagectomy. We found no difference in survival or morbidity between transhiatal and transthoracic esophagectomy. Overall 5-year survival for stage I and II disease was 86%. For stage III and IV disease, 5-year survival was 14.5%. Aggressive surveillance of Barrett's esophagus facilitates the discovery of early disease. Esophagectomy for adenocarcinoma can result in cure of early cancers and improved palliation of more advanced disease. PMID- 1642538 TI - Effect of helium and oxygen on airflow in a narrowed airway. AB - A mixture of 80% helium and 20% oxygen has physical properties that increase airflow and decrease resistance in the airway when used as a portion of inspired gas. This study was designed to demonstrate and quantify the effects of a helium oxygen mixture in a normal airway and when airway resistance is increased. Thirty healthy volunteers were studied breathing room air and the helium-oxygen mixture through a normal airway and an airway that included a resistor. Pulmonary function tests, directed by a registered respiratory therapist, were performed on all subjects using a computerized spirometer. The functional vital capacity, one second forced expiratory volume, half-second forced expiratory volume, and peak inspiratory flow rate were analyzed. There was a statistically significant increase in 1-second forced expiratory volume using a helium-oxygen mixture in a normal airway. All pulmonary function test scores statistically improved when volunteers inspired helium and oxygen through the restricted airway, demonstrating that helium and oxygen can increase airflow in the presence of an increased airway resistance. This substantiates a role for helium and oxygen in treating conditions associated with decreased airway size and increased airway resistance. PMID- 1642539 TI - Carotid body tumor. AB - To better define the management and behavior of carotid body tumors, a 34-year surgical experience with 33 tumors in 30 patients was reviewed. There were 20 women and 10 men with an age range of 20 to 78 years. All but one presented with a neck mass. Arteriography was performed on 21 patients and was diagnostic in every case. There was no surgical mortality. Complications occurred in eight patients (27%), and one long-term neurologic deficit occurred. Three of 33 tumors were malignant, and aggressive resection of all approachable disease with radiotherapy for unresectable metastases led to prolonged survival in each case. Carotid body tumors present with neck mass. Arteriography is diagnostic and surgery is indicated. Even for malignant tumors and metastases, aggressive resection and radiotherapy are indicated. PMID- 1642540 TI - Late results of suprarenal Greenfield vena cava filter placement. AB - Placement of the Greenfield filter above the renal veins was necessary in 71 (9%) of 821 total patients in the filter registries of two institutions. The status of 60 patients (85%) could be verified, with follow-up data ranging from 18 months to 16 years (average, 53 months). Of 24 deaths (34%), none was from recurrent embolism or renal failure; death was most commonly associated with a malignant neoplasm. The recurrent embolism rate was 4%, identical to the infrarenal experience. Duplex evaluation of the filters in 22 patients, representing the majority (61%) of living patients, showed that all the filters were patent. Sixteen patients (41%) had lower-extremity edema that predated filter insertion, and in no patient did the results of noninvasive venous studies worsen. Filter fracture (two patients) or distal migration (two patients) had no clinical sequelae, and there was no evidence of renal dysfunction. For thrombus extending to the level of the renal veins or within them and for pregnant patients or women of childbearing age, suprarenal placement of the Greenfield filter is safe and effective, with no filter obstruction seen in follow-up extending to 16 years. PMID- 1642541 TI - Axillary-popliteal artery bypass provides successful limb salvage after removal of infected aortofemoral grafts. AB - Axillary-popliteal artery bypasses were placed to revascularize 28 extremities for 17 patients who were undergoing removal of infected aortofemoral grafts. Polytetrafluoroethylene (PTFE [polytef]) material was anastomosed to the above knee popliteal artery in 22 cases and to the below-knee popliteal artery in six limbs. All but one patient had axillary-popliteal grafts in place before excision of the aortic graft. In 12 groins, vein-patch angioplasty was performed after removal of the infected aortic graft to provide retrograde pelvic perfusion and maintain femoral patency for future reconstruction. Three patients (18%) died of septic-related, multisystem organ failure. With a mean follow-up of 25 months, primary patency was 75% at 1 year and 43% at 2 years. Secondary patency, maintained by thrombectomy (n = 7), revision (n = 3), and conversion to warfarin sodium (Coumadin) therapy (n = 6) was 100% at 2 years, and limb salvage was achieved for all surviving patients. PMID- 1642542 TI - Colon infarction after ruptured abdominal aortic aneurysm. AB - Colon infarction is a lethal complication of ruptured abdominal aortic aneurysm. We compared multiple anatomic, hemodynamic, and clinical features in 25 patients with ruptured abdominal aortic aneurysm who suffered colon ischemia and 25 initial survivors of ruptured abdominal aortic aneurysm in whom this complication did not develop. Prior impressions notwithstanding, preoperative shock or volume administration did not correlate with the development of colon ischemia, nor did aneurysm location, cross-clamp site, graft type, or inferior mesenteric artery patency. However, patients with colon ischemia had a significantly lower perioperative cardiac output and were significantly more likely to have received alpha-adrenergic vasoconstrictor agents. Seventeen patients (68%) with colon ischemia died compared with nine patients (36%) without colon ischemia. Perioperative maintenance of cardiac output and avoidance of alpha-adrenergic vasopressor agents are critical elements in prevention of this lethal complication. PMID- 1642543 TI - Aortic aneurysmal disease. A generalized dilating diathesis. AB - The association of dilated peripheral arteries with aortic aneurysmal disease has previously been suspected, but is not well documented. To test this association, the diameters of the common femoral, popliteal, brachial, common carotid, internal carotid, and external carotid arteries were measured with a color-flow duplex scan in 30 control subjects and 36 patients with aortic aneurysm matched for age, sex, smoking habits, and hypertension. Mean peripheral artery diameter was significantly greater in patients with aortic aneurysm than in controls at all measurement sites. Peripheral artery dilatation was identified at sites that are seldom, if ever, involved in atherosclerosis. These findings lend support to the view that there is a generalized dilating diathesis in aortic aneurysmal disease that may be unrelated to atherosclerosis. PMID- 1642544 TI - The 'absent' appendix. AB - During an operation for suspected appendicitis, the surgeon concluded that the appendix was absent. The causes of this situation are presented and a guide to its management is suggested. PMID- 1642545 TI - Safety of surgical procedures. PMID- 1642546 TI - What is the meaning of labels on trauma care? PMID- 1642547 TI - Genetic characterization of simian immunodeficiency virus isolated from an African mandrill. AB - We constructed an infectious molecular clone of simian immunodeficiency virus from an African mandrill (SIVMND). Upon transfection, this clone directed the production of progeny virus particles infectious to and cytopathic for CD4+ human leukemia cells. Thirteen frameshift proviral mutants with an alteration in the eight open reading frames of SIVMND were generated by recombinant DNA techniques, and were analyzed biologically and biochemically. While mutations in the structural genes gag, pol, and env abolished viral growth and induction of cytopathology, mutants of the vif, vpr, and nef genes were fully biologically active. Of the tat and rev mutants, only one rev mutant grew in CD4+ cells with delayed kinetics. In reporter-based transient expression systems, transactivation potentials of the tat and rev mutants were evaluated. A mutant lacking 2nd coding exon of tat gene exhibited tat activity similar to that of the wild type clone. The infectious rev mutant was partially defective for rev gene activity. PMID- 1642548 TI - Transient expression of the coat protein of sugarcane mosaic virus in sugarcane protoplasts and expression in Escherichia coli. AB - The coat protein (CP) of strain SC of sugarcane mosaic virus (SCMV-SC) was expressed transiently in sugarcane protoplasts after electroporation with one of two plasmids encoding the CP gene. The CP gene was fused with either the cauliflower mosaic virus 35S promoter or the synthetic monocotyledon promoter "Emu". The coat protein gene was also inducibly expressed in Escherichia coli when fused to the trc promoter. The protein expressed in both systems had the same electrophoretic mobility and antigenic specificity as purified SCMV-SC coat protein. Transient expression of the 35S-CP gene in protoplasts could only be demonstrated in Western blots developed with the chemiluminescence enzyme substrate luminol. PMID- 1642549 TI - Expression of nef, vpu, CA and CD4 during the infection of lymphoid and monocytic cell lines with HIV-1. AB - The expression of the capsid antigen (CA) and the two regulatory proteins nef and vpu as well as the CD4 cell surface receptor was followed in HIV-infected lymphoid and promonocytic cells. In the lytic phase of infection all three viral proteins were expressed; production of these proteins coincided with the increase of CA antigen and infectious virus in culture supernatants and with prominent cytopathic effects. After selection of persistently infected cells, the number of lymphoid cells expressing detectable levels of nef decreased to zero; the number of cells positive for CA ranged between 40 to 70%. In chronically infected promonocytic cells nef and vpu expression was reduced to undetectable levels, whereas most of the cells accumulated CA intracellularly. Infectious cell free virus and CA in the supernatant of promonocytic cells had low titers. CD4 surface expression declined in all cell lines investigated before cell free virus was detectable. PMID- 1642550 TI - Comparison of hemagglutinating, receptor-destroying, and acetylesterase activities of avirulent and virulent bovine coronavirus strains. AB - Hemagglutinating and acetylesterase functions as well as the 124 kDa glycoprotein were present in the highly cell-culture adapted, avirulent bovine coronavirus strain BCV-L9, in the Norden vaccine strain derived from it, and in 5 wild-type, virulent strains that multiplied in HRT-18 cells but were restricted in several types of cultured bovine cells. The BCV-L9 and the wild-type strain BCV-LY-138 agglutinated chicken and mouse erythrocytes. The acetylesterase facilitated break down of the BCV-erythrocyte complex with chicken but only to a minimal extent with mouse erythrocytes in the receptor-destroying enzyme test. Purified preparations of the vaccine and the wild-type strains agglutinated chicken erythrocytes at low titers and mouse erythrocytes at 128 to 256 times higher titers whereas receptor destroying enzyme activity was detectable only with chicken erythrocytes. When wild-type strains were propagated in HRT cells at low passage levels, they produced 5 x 10(5) to 4.5 x 10(6) plaque forming units per 50 microliters which agglutinated erythrocytes from mice but not from chickens. Diisopropylfluoro-phosphate moderately increased the hemagglutination titers, but completely inhibited the receptor destroying enzyme of purified virus of all strains. It had virtually no influence on the plaque-forming infectivity of the different BCV strains. The acetylesterase of strain BCV-L9 reacting in the receptor-destroying enzyme test was stable for 3 h at 37 and 42 degrees C. It was inactivated within 30 min at 56 degrees C while the hemagglutinin function of this strain was stable for 3 h at 37, 42, and 56 degrees C, but it was inactivated at 65 degrees C within 1 h. PMID- 1642551 TI - Ultrastructure of lymphocystis disease virus (LDV) as compared to frog virus 3 (FV3) and chilo iridescent virus (CIV): effects of enzymatic digestions and detergent degradations. AB - Ultrastructure of fish lymphocystis disease virus (LDV), the largest of all known icosahedral viruses, has been studied under electron microscopy using enzymatic digestions and detergent degradations. LDV structure appeared roughly the same as those of frog virus 3 (FV3) and chilo iridescent virus (CIV), two other well known viruses of the family Iridoviridae, although the great flexibility of its capsid as observed on negatively stained and shadow cast particles, and its three electron dense layers visualized in ultrathin sections, differed from observations made with the two other viruses. Specific degradation of the virions with enzymes or detergents revealed that the composition of the three iridoviruses was very much alike. In fact, their capsid was composed of two layers as observed in negative staining: an external one, which was removed following digestion with proteinase K, and an internal one which could be digested with phospholipase A2. Thus, the outermost layer is probably made of surface protein units, more or less tightly bound to each other, while the internal one would be a lipoprotein membrane. Consequently, these three iridoviruses appeared structurally related. PMID- 1642552 TI - The synergistic neutralization of Rift Valley fever virus by monoclonal antibodies to the envelope glycoproteins. AB - A panel of monoclonal antibodies (MAbs) mapping to different antigenic sites on the RVFV G1 and G2 proteins were used to examine the mechanisms involved in neutralization of the virus. Three types of synergistic neutralization of RVFV were observed on mixing various pairs of MAbs. Firstly, enhanced neutralization occurred for two MAb pairs that showed augmented binding for G2. These comprised a combination of a neutralizing MAb with a non-neutralizing antibody, as well as two antibodies which were non-neutralizing individually. In the second category, synergistic neutralization was observed between combinations of MAbs for which increased binding had not been detected. Lastly, mixtures of G1 and G2-specific MAbs were also capable of enhancing neutralization. Post-adsorption neutralization assays revealed that some MAbs neutralized cell-attached virus efficiently, indicating that they can neutralize by inhibiting the infection process after virus attachment. MAbs mapping to G1 IIe, G2I b and G2I c were unable to neutralize adsorbed virus and thus probably neutralize by preventing virus attachment to cells. Several G1-reactive MAbs displayed low level post adsorption activity, suggesting they may be capable of inhibiting RVFV infectivity at different stages of the replication cycle. PMID- 1642553 TI - Radioactive and enzymatic cloned cDNA probes for bovine enteric coronavirus detection by molecular hybridization. AB - Genomic RNA of F15 strain bovine enteric coronavirus (BECV) was cloned in E. coli. Three clones (174, 160, PG78), selected in the cDNA library, including a large portion of the nucleocapsid (N), matrix (M) and peplomeric (S) protein genes, were used as probes for a slot blot hybridization assay. Two probe labelling techniques were compared, radiolabelling with 32P and enzymatic labelling through covalent linkage to peroxidase and chemiluminescence detection. The radioactive probe 174 detected as little as 1 to 3 pg of viral RNA, while the less sensitive enzymatic probe could not reveal more than 100 pg of RNA. No significant detection amplification was achieved when a mixture of the three probes was used. Probe 174 allowed specific identification for BECV. No hybridization was noticed either with rotaviruses or even with other antigenically unrelated members of the family Coronaviridae such as transmissible gastroenteritis virus. The test proved valid for detection of BECV in the supernatant of infected HRT-18 cells: genomic RNA could be detected after direct spotting of samples, but prior nucleic acid extraction after proteinase K treatment improved virus detection. BECV diagnosis in faecal samples using enzymatic probe was compared with conventional diagnostic methods. PMID- 1642554 TI - Structural variability of env and gag gene products from a highly cytopathic strain of HIV-1. AB - The glycoprotein precursor of the highly cytopathic Zairian virus HIV1-NDK synthesized in CEM leukemic cells displayed a molecular mass of 140 kDa (gp140) as compared to the 160 kDa of gp160 of HIV1-LAV prototype strain. This precursor was cleaved to produce a smaller than prototype extra-cellular envelope glycoprotein (gp100) and a transmembrane component with a usual size (gp41). Immunoprecipitates from tunicamycin-treated infected cells demonstrated the presence of a non-glycosylated precursor of 100 kDa for HIV1-LAV prototype strain and 90 kDa for HIV1-NDK. Digestion of labeled precipitates with a mixture of endoglycosidase F and glycopeptidase F reduced the size of HIV1-LAV gp160 and gp120 to 100 and 60 kDa, respectively, while HIV1-NDK gp140 and gp100, after treatment with the same enzymes, displayed an apparent molecular mass of 90 kDa and 55 kDa, respectively. From these data we conclude that HIV1-LAV gp120 and HIV1-NDK gp100 differ both in their proteic moiety (60 kDa and 55 kDa, respectively) and in their carbohydrate moiety (60 kDa and 45 kDa, respectively). These differences could not be deduced from the available gene sequences of the two viruses. A chimeric virus containing the first 124 amino acid residues of the envelope glycoprotein coded by HIV1-LAV sequence and the rest by HIV1-NDK displayed normal size envelope glycoproteins, demonstrating the involvement of this N-terminal sequence in the alteration of the molecular mass characteristic of HIV1-NDK gp140 and gp100. Finally, characterization of the gag gene products from both strains demonstrated that HIV1-NDK p18 and p15 have a slower electrophoretic mobility as compared to its HIV1-LAV counterparts. Therefore, structural properties of HIV1-NDK env and gag products, reflected by their unusual electrophoretic mobilities, may be responsible for HIV1-NDK biological properties. PMID- 1642555 TI - Detection of a hepatitis B virus variant with a truncated X gene and enhancer II. PMID- 1642556 TI - Characteristics of a cetacean morbillivirus isolated from a porpoise (Phocoena phocoena). AB - A virus isolated from a porpoise during the 1988 seal epizootic was shown to be a morbillivirus. In order to determine the relationship of the virus to phocine distemper virus (PDV) a battery of monoclonal antibodies raised against canine distemper virus (CDV), PDV or the porpoise isolate were assessed for their ability to bind to CDV, PDV or porpoise virus epitopes in indirect immunofluorescence assays and ELISAs. The porpoise isolate contained several unique epitopes and several epitopes present on CDV and PDV were absent on the porpoise isolate. The data presented in this study indicate that the porpoise virus is an antigenically distinct morbillivirus and as such has been tentatively named as delphinoid distemper virus (DDV). PMID- 1642557 TI - PCR-amplification of influenza A virus specific sequences. AB - The possibilities of PCR-technique for rapid influenza virus A diagnostic using universal and M- or NS- gene specific primers were demonstrated. The results of PCR-analyses of specimens from people correlated with virological, serological and immunochemical data and the results of spot-hybridization test. PMID- 1642558 TI - An epidemic of non-A, non-B hepatitis in south Delhi: epidemiological studies and transmission of the disease to rhesus monkeys. AB - In November 1987 an epidemic of NANB-hepatitis broke out in a residential colony of South Delhi which lasted for nearly two months. The epidemic was caused due to the sewage contamination of the drinking water supply. Analysis of the epidemiological data showed that the disease was more common in the younger age group of 11-20 years and that both sexes were equally prone to the disease. The disease could be transmitted to rhesus monkeys by intravenous inoculation of the stool extracts from the patients. Experimentally infected monkeys showed elevated levels of serum aminotransferases and excreted the infectious agent in the stools. Hepatic lesions characteristic of enteric non-A, non-B hepatitis were observed in an infected monkey. PMID- 1642559 TI - Increased HIV-1 production in chronically infected H9 cells grown in protein-free medium. AB - Human T cell line H9 was established in a protein-free 1:1 mixture of Ham's F-12 and IMDM. After 230 passages (3 years) in protein-free medium, the cells designated H9-PF were infected with HIV-1. The infectivity titers of HIV-1 in cell culture medium were monitored by determining the median tissue culture infectious doses (TCID50). Additionally, the production of viral antigen in cells was measured by an immunoenzymatical alkaline phosphatase anti-alkaline phosphatase (APAAP) method using a monoclonal antibody against HIV-1-p24 antigen. In acutely infected H9-PF and H9 cultures similar TCID50 values and percentage of cells positive for p24 antigen were found. In contrast, both TCID50 values and percentage of cells positive for p24 antigen were by far greater in chronically infected H9-PF than in H9 cultures. PMID- 1642560 TI - In vitro expressed HPV 8 E6 protein does not bind p53. AB - The oncogene E6 of human papillomavirus 8, which is associated with skin cancers in epidermodysplasia verruciformis, was transcribed and translated in vitro. The resulting 17 kDa protein did not bind to the cellular p53 in contrast to E6 of HPV16. PMID- 1642561 TI - The IgA and subclass IgG responses and protection in mice immunised with influenza antigens administered as ISCOMS, with FCA, ALH or as infectious virus. AB - Comparative studies on the local IgA, and circulating IgG subclass antibody responses of mice to A/Sichuan/2/87 (H3N2) influenza virus surface antigens administered with different carrier or delivery systems by the parenteral route, were carried out. The results obtained were compared with the responses observed following live influenza virus infection, and the protection afforded to these animals by these various preparations determined. Infection with live virus elicited early and high levels of protection against homologous virus challenge and this correlated with both local IgA and circulating IgG2a antibody levels. When incorporated into immunostimulating complexes (ISCOMS), A/Sichuan surface antigens promoted high levels of local IgA and circulating IgG1 antibody, and achieved a more rapid and more solid immunity against homologous virus challenge infection, than that elicited by the same surface antigens administered alone or together with Freund's complete adjuvant or alhydrogel. PMID- 1642563 TI - Fitting multichannel-compression hearing aids. AB - Multichannel hearing aids have been introduced recently in clinical practice. In this paper, some advantages and disadvantages of multichannel hearing aids are discussed. The advantages include an improved use of compression. However, the number of settings will be larger in multichannel hearing aids and exact knowledge of the goal to be pursued by compression is more necessary than ever. Inexactness of the definitions of these goals may have been a reason for the contradictory results in the studies on multichannel compression. A number of requirements must be fulfilled for a successful application of multichannel compression. One of these is detailed knowledge about the perception of suprathreshold signals. For that reason, an extension of the battery of tests commonly used in rehabilitative audiology is necessary. Another requirement is that the fitting strategy is determined by the purpose of applying compression. The objectives will be different for compression limiting and syllabic compression. A fitting procedure used in clinical practice has to take into account some limitations in the fitting time available. A number of possible fitting tools are discussed. Two strongly different fitting strategies for the same commercially available three-channel compression aid illustrate fundamental differences in fitting philosophy. PMID- 1642562 TI - Acute and latent infection of mice immunised with HSV-1 ISCOM vaccine. AB - The effect of immunisation with an HSV-1 antigen preparation (containing at least 6 viral glycoproteins) on primary infection with HSV and the establishment of latency, was assessed in two mouse models (involving either skin or corneal challenge with virus). The vaccine preparation, given either with Freund's complete adjuvant or aluminium hydroxide gel or in the form of immunostimulating complexes (ISCOMS), induced high ELISA antibody responses (highest with HSV as the ISCOM preparation) and low levels of neutralising antibody. In both models, immunisation with the HSV ISCOM preparation significantly reduced the incidence of zosteriform spread of virus and the severity of disease and, in some cases, the incidence of latent infection in sensory ganglia. In the eye model it was possible to show that immunisation with the HSV ISCOMS restricted the establishment of latency almost entirely to the ophthalmic part of the trigeminal ganglion. Protection from establishment of latency correlated with prechallenge antibody levels. PMID- 1642564 TI - Diagnosis of middle ear disease with eardrum perforation by a newly developed sweep frequency measuring apparatus. AB - Dynamic characteristics of an artificial middle ear model with and without eardrum perforations were measured with our newly developed sweep frequency measuring apparatus. Then, the dynamic characteristics of patients with chronic otitis media having eardrum perforations and with traumatic perforations were measured with this apparatus, and the results were compared with those of the artificial middle ear model with an eardrum perforation. The comparison leads to the conclusion that the middle ear condition of patients with eardrum perforations can be distinguished on the basis of their measurement results. Furthermore, the ossicular chain conditions of patients with eardrum perforations can be diagnosed after putting a paper patch on the eardrum perforation. Therefore, this apparatus seems to be highly useful in the diagnosis of both ossicular chain disorders and eardrum perforations. PMID- 1642565 TI - Growth of evoked otoacoustic emissions during the first days postpartum. A preliminary report. AB - Evoked otoacoustic emissions (EOAEs) were recorded twice in 20 ears of 15 newborns. The recordings were performed in a room of the well baby ward, using the ILO88 in its default setting, i.e. with click stimulation. On the first test occasion, the infants were between 3 and 51 h of age, and EOAEs were identified in 10 ears. On the second test occasion, while the infants were at least 1 day older (range 42-107 h), EOAEs were present in all ears. The second EOAE was stronger, so the EOAE appeared to grow in the first days postpartum. This might be due to middle ear clearance of amniotic fluid, shortly after birth. The results of the EOAEs of the second examination were compared with 10 EOAEs in adult ears. The response levels of the newborns were significantly higher than in the adults. The (cross)-correlation peak value of the two tests' waveforms is over 0.75, however sometimes only after filtering around the most pronounced emission frequencies. The study proves that newborns failing the EOAE screen in the first 24 h after birth can pass if retested 1 day later, simply because of growth of EOAE strength. PMID- 1642566 TI - Left-right asymmetries in hearing threshold levels in three age groups of a random population. AB - The average asymmetry between the hearing threshold levels in the left and right ears was analyzed in a random population (n = 3487) representing a normal population. Males and females of age groups 5-10 years, 15-50 years and over 50 years were analyzed separately. A significant average inferiority of the hearing in the left ear was found at high frequencies, especially at 3-6 kHz, among adult males and females but not among children. A slight but statistically significant average superiority of the left ear at low frequencies was noted in all age groups. At corresponding hearing threshold levels at 4 kHz, the average inferiority of the left ear in the male population was significantly greater among subjects aged 15-50 years than among older subjects. In conclusion, the inferiority of hearing in the left ear at 4 kHz seems to be associated more with noise damage than with presbyacusis. The average interaural difference at 4 kHz was significantly more marked among subjects aged 15-50 years than among older subjects when analyzed at the corresponding threshold levels. These findings indicate a pathophysiological difference between noise damage and presbyacusis. PMID- 1642567 TI - Support for Corso's hearing loss model. Relating aging and noise exposure. AB - A brief review is provided of the variable ratio model [Corso, Audiology 1980;19:221-232] for partitioning the effects of age and noise exposure in cases of occupational hearing loss. Data are presented from Rosenhall, Pedersen, and Svanborg [Ear Hear 1990;11:257-263] which support the variable-ratio model. Suggestions are offered for the application of the model in medico-legal cases of permanent hearing damage due to excessive noise exposure. PMID- 1642568 TI - Psychological and audiological correlates of perceived tinnitus severity. AB - Beliefs and attitudes towards tinnitus have been found to play an important role in the process of rehabilitation. The relationship between audiological, psychological and psychosomatic factors (self-assessment of vertigo and headache and the perceived severity of tinnitus) was investigated in a clinical population of 163 subjects. Audiological descriptives comprised pure-tone average (dB HL), etiology of hearing loss, duration of tinnitus and tinnitus localisation. Perceived severity of tinnitus was assessed with a questionnaire focusing on tinnitus impact on aspects of quality of life, concentration and sleep. A 28-item handicap and support questionnaire was used and factor analysed, resulting in three factors: perceived attitudes, social support and disability/handicap. Tinnitus severity was significantly related to perceived attitudes. The influence of social support on tinnitus severity did not seem to be crucial. The results showed that significantly more women than men complained about vertigo. Unilateral tinnitus localisation was also more prevalent in females. The subjects with multiple tinnitus localisations were older and had significantly more sleep disturbance than subjects with tinnitus localized to the ears only. In accordance with previously reported observations, the frequency of headaches was strongly correlated with the severity of tinnitus. PMID- 1642569 TI - The use of a BF3 remmeter to calibrate neutron activation foils in the medical linear accelerator environment. AB - A technique has been developed for radiation protection purposes whereby it is possible to measure the dose-equivalent due to neutrons from a dual energy medical linear accelerator using a conventional BF3 neutron remmeter to calibrate gold foils. This technique has been applied to measuring the neutron dose equivalent from a Philips SL75-20 medical linear accelerator. The tenth value distance for the entrance maze is 3.3 +/- 0.5m compared to a typically quoted value of 5m. This suggests that the use of wood and boron tiles in the construction of the entrance maze can reduce neutron propagation down the maze. PMID- 1642571 TI - X-ray field misalignment in screening mammography. PMID- 1642570 TI - Automatic counting of nuclear tracks. AB - Two software packages designed for automatic counting nuclear tracks are tested and compared. The image processing in the first package is divided into three parts segmentation, speckle elimination and removal of ill-formed track holes. The second package is also divided into three parts but the last part is modified such that the track holes with white centres are filled by the program. The processes in the second package are done by the use of mathematical morphology. From the test, it was found that the first package has severe limitations for the working range. The second package provides a greater working range but the running time of the program is longer than that of the first package. PMID- 1642572 TI - Do changes in transcardiac impedance modulation correlate with haemodynamic status? AB - Implantable cardiac pacemakers and defibrillators have the ability to revert a variety of arrhythmias to normal sinus rhythm. For correct operation, such devices require accurate arrhythmia classification. Arrhythmia classification by these devices could be improved with the addition of a suitable haemodynamic sensor. This study investigated the use of transcardiac impedance for haemodynamic sensing. Ventricular fibrillation, ventricular tachycardia, electro mechanical dissociation and five rates of ventricular pacing, each having a different associated level of haemodynamic compromise, were induced in each of seven mongrel dogs. The amplitude responses of the modulations of transcardiac impedance were compared with those of arterial pulse pressure (an established measure of haemodynamic status), and changes in cycle length. The correlation coefficient for changes in transcardiac impedance modulation amplitude and arterial pulse pressure was found to be 0.89. For transcardiac impedance modulation amplitude and cycle length, the correlation coefficient was 0.77, and for arterial pulse pressure and cycle length, the correlation coefficient was 0.85. In the acute anaesthetised dog, changes in the amplitude of transcardiac impedance modulations were shown to reflect different levels of haemodynamic status. PMID- 1642573 TI - Auditory P300 studies in schizophrenic subjects and their first degree relatives. AB - Nineteen subjects with schizophrenia, 6 subjects with related disorders (schizophrenic spectrum disorders (S.S.D.)), and 20 unaffected first degree relatives from a sample of schizophrenic pedigrees, together with 35 normal control subjects, had auditory P300 evoked responses measured, using the "odd ball" paradigm for stimulation. Bipolar recording on the midline (CZOZ) and two contralateral sites (CZ-mastoid) was carried out. It was found that approximately 40% of schizophrenics/S.S.D.'s had abnormal P300 responses. Abnormalities were seen in latency, RMS response voltage and in the left side response--right side response cross correlation coefficient. Schizophrenics/S.S.D.s showed responses which were topographically different than those of normal controls. Significant left-side/right-side response voltage asymmetry was not observed. In our study, only 10% of unaffected relatives of schizophrenics/S.S.D.'s showed abnormal P300 responses. PMID- 1642574 TI - Tissue analysis using dual energy CT. AB - A new dual-energy x-ray CT algorithm is presented which makes use of both pre- and post-reconstruction data in an iterative manner to achieve accurate beam hardening correction and decomposition into basis materials. The technique does not require a calibration phantom and also does not require accurate estimation of the effective energies of the polyenergetic x-ray beams. It does however, require a knowledge of the incident x-ray spectra. For the situation where the incident spectra are unknown, a method is given whereby sufficiently accurate approximations to the spectra can be determined from attenuation measurements. Decomposition into basis materials makes use of spatial and energy information and an 'a priori' knowledge of the composition and attenuating properties of various tissue types. Any total number of basis materials may be used within the limitation that a subset containing a maximum of three materials is used for any individual pixel. Results of a computer simulation show that the algorithm produces accurate measurements of the concentrations of both high and low atomic number materials such as bone mineral, collagen, fat and air. However the results of a phantom study show that the measurement of the concentrations of low atomic number basis materials may be subject to systematic errors arising from uncertainties in the published values of linear attenuation coefficients. PMID- 1642575 TI - A visual evoked response simulator. AB - A Visual Evoked Response (VER) phantom, simulating a normal waveform response, has been designed to assist with calibration and quality assurance of ophthalmic electrophysiological instrumentation. This VER SIMulator (VERSIM) is based on a simple microprocessor design with a digitised waveform stored as an array in memory and converted to an analog signal when output. Frequency is controlled by a software delay between each byte of data output and a voltage divider network defines the range of voltages. To simulate a subject isolated from the electrical mains supply the VERSIM is battery powered. PMID- 1642576 TI - Optimization of a cord shielding technique for electrons. AB - Large anterior electron fields are sometimes used to irradiate the neck when treating head & neck tumors. To offer a degree of spinal cord shielding, wax bolus, approximately the width of the vertebral bodies, is placed on the immobilization shell. The thickness of the bolus is adjusted so that the radiological depth of the anterior edge of the vertebral bodies is equal to the R80 depth for the energy used. This approach ignores electron scattering. Using a CT study of a thyroid cancer patient, neck contours were generated at 0.5 cm intervals and entered into the Alberta Treatment Planning system. Internal contours for the trachea and vertebral bodies were added and CT information was used for treatment planning purposes. The bolus outline was added as described above, and the dose calculated using a 3D implementation of the M.D. Anderson (Hogstrom) algorithm. The calculation shows that the simple bolus technique described above is inappropriate. The spinal cord is adequately shielded, but the target volume is not covered by the 80% isodose line. Qualitatively, the results can be explained by the lateral scatter non-equilibrium introduced by the bolus. By iteratively adjusting the shape and thickness of the wax bolus and recalculating the dose distribution, we were able to better fulfill the dose prescription. Comparison with measured data shows reasonable, but not perfect agreement. In conclusion, electron beam treatments must be examined closely to ensure that the treatment goals are met. In some cases, treatment integrity may be compromised by incorrect assumptions regarding the nature of the electron transport and dose deposition. PMID- 1642577 TI - A contrast-detail study of interpolated scatter and glare correction of digital fluoroscopic images. AB - A scheme to correct for the effects of scattered radiation and veiling glare on the contrast of digital fluoroscopic images was investigated. The correction scheme is based on using spatial interpolation of signals generated in the shadows of a lead disk array, placed in the radiation beam. Contrast-detail plots obtained using the Leeds TO.10 test object, for corrected images were compared with those for unprocessed images, for images processed using digital contrast enhancement and for images acquired using a grid. It was found that substantial improvements in image contrast were obtained using the correction scheme. PMID- 1642578 TI - Deep vein thrombosis: aetiology, prevention and management. PMID- 1642579 TI - Deep vein thrombosis prophylaxis: a survey of current practice in Australia and New Zealand. AB - A survey of current practice for deep vein thrombosis (DVT) prophylaxis was undertaken in Australia and New Zealand. The most common indications for prophylaxis were a history of thrombo-embolism, the type and length of surgery and obesity. Prophylaxis was used in 65% of patients having hip surgery and in 39% undergoing knee surgery. In general surgery the corresponding rate was around 67% for colorectal surgery, hepatobiliary, upper gastrointestinal and major abdominal vascular surgery. Apart from open-heart cardiothoracic surgery (66%), use in other specialties was less than 50%. Physical methods (anti-embolism stockings, calf stimulation and calf compression devices) were most commonly used for prophylaxis (46%) with heparin being used by 40%. The main side effect reported with heparin was bleeding (18%). The estimated incidence of DVT and pulmonary embolus (PE) was 2.8 and 0.4% for general surgery, 2.7 and 0.7% for orthopaedic surgery and 6.6 and 1.3% for hip surgery. Intravenous heparin followed by oral anticoagulants was the most commonly used treatment for established DVT and nearly all respondents used intravenous heparin and oral anticoagulants for treatment of PE. Venography was the favoured objective test for diagnosing DVT. The principal reason for considering a change in prophylactic policy was the potential availability of an agent with increased efficacy and a reduced incidence of haemorrhagic complications. PMID- 1642580 TI - Prophylaxis against venous thrombosis after total hip arthroplasty. AB - Venous thrombosis rates were compared in 200 patients undergoing total hip arthroplasty and randomized to receive either fixed mini-dose warfarin (1 mg daily) or adjusted-dose warfarin to maintain an international normalized prothrombin ratio (INR) of 2.0-4.0. Bilateral lower limb venography was performed between days 11 and 13 inclusive. Fixed mini-dose warfarin was associated with a significantly higher rate of total thrombosis (P less than 0.05). General anaesthesia was associated with a significantly higher rate of thrombosis than spinal anaesthesia (P less than 0.05). Adjusted-dose warfarin was associated with more bleeding complications than mini-dose warfarin although these were not attributable to excessive anticoagulation. A single death from pulmonary embolus occurred in the early postoperative period in a patient receiving adjusted-dose warfarin. PMID- 1642581 TI - Duplex scan surveillance of infra-inguinal bypass grafts: the case for selectivity. AB - A consecutive series of 270 non-reversed infra-inguinal saphenous vein bypass grafts performed by the same surgeon between January 1986 and January 1991 was reviewed. The series included 250 in situ and 20 translocated non-reversed grafts. The aims were to calculate the number of duplex scans that would have been required for surveillance, to determine the value of a non-selective prolonged scanning regimen and to identify subgroups requiring more (or less) intensive surveillance. Indications were for critical ischaemia in 194 patients, popliteal aneurysms in seven patients and incapacitating claudication in 69 patients. Patients were reviewed at 1 month and then at approximate 6 month intervals for symptoms and with resting and post-exercise ankle pressures. Primary patency of grafts placed to a popliteal distal anastomosis for critical ischaemia was 85% (s.e.m. 9.1%) at 3 years while secondary patency was 94% (s.e.m. 8.1%) at 4 years. Primary patency of grafts placed to a tibial artery or isolated popliteal segment was 68% (s.e.m. 8.4%) at 2 years while secondary patency was 76% (s.e.m. 9.9%) at 2.5 years. The difference in secondary patency between popliteal and tibial grafts was highly significant (P = 0.003). Tibial grafts required significantly more secondary early intervention than popliteal grafts. If recommended protocols for serial duplex scan (DS) surveillance had been followed, a minimum of 960 scans would have been required. If the tibial bypass group only had been monitored, 702 of these scans would have been avoided with a maximum loss of one popliteal graft and no limbs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642582 TI - Coronary artery bypass surgery in young patients. AB - Coronary atherosclerosis is being increasingly observed in young patients. However results of surgery in such patients have so far been disappointing both in terms of operative mortality, symptomatic relief and long-term survival. Reasons given for this include the increased prevalence of risk factors in young patients and a higher incidence of graft occlusion. In the treatment of Asian patients, a further negative factor is the belief that coronary artery disease is more often diffuse and the vessels smaller. Between January 1987 and May 1991, a total of 66 patients under the age of 45 years at the time of surgery had coronary artery bypass grafting performed. The demographic, clinical, angiographic and operative data were analysed. Eighty-nine per cent of the patients were male and their racial distribution was 63% Chinese, 8% Malays, 26% Indians and 3% Others. Their mean age was 40.8 years. The presence of risk factors was high: 45.6% had hypertension; 34.8% were smokers; 21.2% had diabetes mellitus; and 12.1% had hyperlipidaemia. The main indication in these patients was either angina or a previous myocardial infarction (53%). There were no patients with perioperative infarction diagnosed by the presence of new Q wave. There was no hospital death. The stay of the patients ranged from 6 to 28 days with a mean of 10 days. Follow-up ranged from 3 to 54 months. There were no late deaths. It was concluded that there is a high incidence of risk factors among young patients with coronary artery disease, which follows the pattern of many other studies. The operative risk in these patients is low and morbidity is minimal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642583 TI - Radiation therapy of glottic carcinoma: Peter MacCallum Cancer Institute experience. AB - The medical records of patients with T1N0, T2N0 and T3N0 squamous cell carcinomas of the glottis treated at the Peter MacCallum Cancer Institute between January 1983 and October 1988 were retrospectively reviewed. One hundred and twenty-seven patients were identified. There were 93 T1, 26 T2 and eight T3 tumours. These patients were treated with curative radiotherapy (60-70 Gy). The survival from glottic cancer of patients with T1, T2 and T3 tumours at 5 years was estimated to be 97, 62 and 100% respectively. The local disease free survival for T1 and T2 disease at 5 years was estimated to be 82 and 65% respectively. The local disease free survival for T3 tumours at 2 years was estimated to be 63% with 5 year survival not yet reached. The surgical salvage rates for 24 radiotherapy failures were 77, 25 and 66% for T1, T2 and T3 tumours respectively. Radiotherapy remains the treatment of choice for T1 tumours and a viable alternative to primary laryngectomy in more advanced glottic tumours, with salvage surgery in reserve. PMID- 1642584 TI - The abdominal cocoon. AB - Since it was first described in 1978 the abdominal cocoon continues to be a rare cause of intestinal obstruction. So far this rare condition where the small intestine is encased in a fibrous membrane has been reported only in females. Diagnosis is usually made at laparotomy and the treatment of choice is lysis of adhesions. Proper recognition of this benign condition will result in the correct management of it and prevent unnecessary bowel resections. Five new cases including one male patient, together with a review of previous reports in the English literature, are presented. PMID- 1642585 TI - Photodynamic therapy in the treatment of subcutaneously implanted human bladder tumour. AB - Photodynamic therapy (PDT) is an experimental treatment modality for malignant tumours. The effect of PDT with haematoporphyrin derivative (HpD) was studied using a human bladder tumour (BL-17) which was implanted subcutaneously (s.c.) into immunodeficient Balb/c nude mice. This model is only suitable for short-term investigation of PDT because of the high mortality that arises due to the immune deficiency of the animals. In a short-term observation (2 weeks post-treatment), HpD sensitized PDT was effective in the control of tumour growth, with 71% of tumours cured. The effect of PDT was found to be highly dependent on doses of HpD and/or the activating laser light. The comparison of PDT effects of the gold metal vapour laser (GMVL) and argon ion pumped dye laser (AIPDL) indicated that no significant difference exists between these two different laser sources for PDT. The irradiation with laser light alone and the administration of HpD alone had no significant effect on tumour growth. PMID- 1642586 TI - Management of the airway in oral and oropharyngeal resections. AB - A tracheostomy is the traditional method of maintaining an airway after major oral and oropharyngeal resections. Postoperative endotracheal intubation was used for 19 patients who underwent major oral and oropharyngeal resections over a 3 year period at the Royal Adelaide Hospital. This appears to be a safe alternative to tracheostomy if intensive care facilities are available. PMID- 1642587 TI - Linitis plastica carcinoma of the colon mimicking Crohn's colitis. AB - Primary linitis plastica carcinoma of the colon is an uncommon morphological type of colorectal carcinoma. Linitis plastica of the stomach may spread to the colon producing a similar lesion to primary colonic linitis plastica. This case report describes a case of linitis plastica of the colon that had many of the clinical, endoscopic, radiological and operative features of Crohn's colitis. The precise origin of the linitis plastica carcinoma was not clear: it may have been clonic or gastric, although the former is favoured. This case illustrates a number of facets of this unusual colonic carcinoma. PMID- 1642588 TI - Major gastrointestinal haemorrhage from a metastatic testicular teratoma. PMID- 1642589 TI - Life-threatening glossopharyngeal neuralgia. AB - Glossopharyngeal neuralgia is a rare condition that, on occasions, may be associated with cardiac dysrhythmia. This case report describes the case of an 86 year-old woman whose glossopharyngeal neuralgia was complicated by life threatening dysrhythmias and who was cured by posterior fossa rhizotomy. PMID- 1642590 TI - Psoas abscess following ingestion of psoas. AB - A case of right psoas abscess that was caused by duodenal perforation following the ingestion of a wooden skewer from a filet mignon is presented. Surgical repair of the perforation, drainage of the abscess and 5 days of intravenous antibiotics resulted in prompt recovery. PMID- 1642591 TI - Spontaneous rupture of a splenic artery aneurysm. PMID- 1642592 TI - Two difficult cases of craniocervical instability. PMID- 1642593 TI - Mucinous cystadenoma of the appendix: an unusual cause of recurrent intussusception in an adult. PMID- 1642594 TI - Veterinary education--the three-fold path to reform. PMID- 1642595 TI - Efficacy and safety of ivermectin applied topically to cattle under field conditions in Australia. AB - Fifteen controlled field trials were conducted to evaluate the efficacy against gastrointestinal nematodes and safety of ivermectin when applied topically to cattle in Australia. Three hundred and fifty-one cattle received ivermectin, and 88 were untreated controls. The trials were conducted in 3 States and included a variety of cattle breeds and environmental conditions. Faecal samples were collected before treatment and 11 to 14 days after treatment for nematode egg counts. Data from these trials show that under Australian conditions, ivermectin applied along the mid line of the back from the withers to the sacral region at a dose rate of 500 mcg/kg body weight, effectively controlled gastrointestinal nematode infections, and did not produce unacceptable adverse reactions in the animals. PMID- 1642596 TI - Cryptococcosis in seven horses. AB - The clinical, radiographic and post-mortem findings in 6 horses with cryptococcal pneumonia and one horse with an abdominal cryptococcal granuloma are described. In pulmonary cryptococcosis, the lesions were either diffuse and multiple, with bilateral lung involvement, or localised mainly to the dorsocaudal region of one lung. The cases of diffuse multiple cryptococcosis were thought to be associated with haematogenous spread of the fungus after gastrointestinal infection and dissemination from regional lymph nodes. The localised form of the disease was thought to have been associated with inhalation of cryptococci. In all cases of pulmonary cryptococcosis, encapsulated yeast-like organisms were demonstrated in Wright's-stained sediment of tracheal washes. In the horse with the abdominal granuloma, cryptococci were present in a fine needle aspirate sample. Isolates of Cryptococcus neoformans var gattii were recovered from 2 of the 5 horses in which cultures were attempted. In addition to a history of previous illness that may have predisposed to infection, most horses in this report had been in areas in which Eucalyptus camaldulensis, or the closely related E rudis, were growing. In humans, an epidemiological relationship between E camaldulensis and infection with C neoformans var gattii has been suggested. Cases of equine cryptococcosis carry a poor prognosis and treatment was not attempted in any of these cases. PMID- 1642597 TI - Molecular pathotyping of two avian influenza viruses isolated during the Victoria 1976 outbreak. PMID- 1642598 TI - Losses of sheep following adverse weather after shearing. PMID- 1642599 TI - Maple syrup urine disease in Poll Shorthorn calves. PMID- 1642600 TI - Protoporphyria in Limousin cattle. PMID- 1642601 TI - Beta-mannosidosis in Salers calves in Australia. PMID- 1642602 TI - Congenital hypotrichosis in Poll Dorset sheep. PMID- 1642603 TI - Pseudomonas pseudomallei infection in camels. PMID- 1642604 TI - Psychomotor change as a feature of depressive disorders: an historical overview. AB - Psychomotor disturbance has generally been viewed as a feature of all depressive disorders, merely varying in severity as a consequence of the mood state. As we have elsewhere argued for psychomotor change being specific to melancholia, its definition, measurement and capacity to sub-type depressive disorders may benefit from close consideration. Here we overview historical views and contemporary measures of psychomotor change, noting variable interest in behavioural manifestations of depression, as against symptoms, over time. PMID- 1642605 TI - Interpersonal sensitivity and the one-year outcome of a depressive episode. AB - Previous studies have demonstrated that abnormalities of personality can contribute to a poor prognosis following a depressive episode. In this study the relevance of a specific personality trait, interpersonal sensitivity, to poor outcome was examined. One hundred and eleven depressives completed the Interpersonal Sensitivity Measure (IPSM) twenty weeks after a baseline assessment. High scores on the IPSM were associated with a poor outcome at one year following the baseline assessment, judged according to whether they had remitted clinically or not and by the degree of change in depression severity measured using the Hamilton and Zung Depression Rating Scales. The relevance of this personality trait to the course and treatment of depression is discussed. PMID- 1642606 TI - Staff response to inpatient and outpatient suicide: what happened and what do we do? AB - Inpatient or outpatient suicide may have a marked effect on the staff or therapist. After reviewing the literature, a practical, clinically-based protocol for managing such an event is described. Additionally, it places one event, the psychological autopsy, within the general context of post-suicide management. PMID- 1642607 TI - General practitioners' reported knowledge about depression and dementia in elderly patients. AB - Previous studies have shown that general practitioners often fail to detect dementia and depression in their elderly patients. The present study aimed to find out how much knowledge general practitioners have of these disorders. The knowledge of 36 general practitioners was assessed and it was found that they had a limited knowledge of the symptoms and signs of dementia and depression. Furthermore, almost 60% of the general practitioners did not know that Alzheimer's disease is the most common dementing disorder. PMID- 1642608 TI - Alcohol-related problems in New Zealand women. AB - As total alcohol consumption has increased this half century in most developed countries, alcohol-related problems have become more frequent. Most research has either studied only men or failed to mention gender. This study examined the prevalence of alcohol problems and their socio-demographic associations in a random sample of New Zealand women. Women of younger age, who were unmarried, well educated, in employment, with child care support and who lived in rural communities saw themselves as having more problems with alcohol. Women who had experienced physical or sexual abuse as adults had increased rates of alcohol problems as did those with more psychiatric morbidity as assessed by the General Health Questionnaire and the short Present State Examination. However, women with multiple social roles, particularly caring responsibilities, were less likely than women with one or two social roles to view themselves as having alcohol problems. The data provided no support for the role strain hypothesis of alcohol abuse. It is argued that the findings support a social explanation for alcohol problems based on varying social sanctions on drinking and alcohol availability rather than a psychoanalytic one of unconscious conflicts over femininity, sexuality or female social roles. PMID- 1642609 TI - Psychiatric morbidity among Dunedin Chinese women. AB - A community postal survey of minor psychiatric morbidity among Chinese women living in Dunedin was conducted. The 28-item version of the General Health Questionnaire (GHQ-28) was used as the case identification instrument. The overall rate of psychiatric morbidity of Dunedin Chinese women did not differ from their European counterparts. The sociodemographic factors found to be associated with minor psychiatric morbidity included having no children, and being either very well or very poorly educated. Among (foreign born) migrants, those who were born in China, whose reason for migration was "follow the lead of their family" or "family reunion", had resided in New Zealand for ten years or more and spoke English infrequently tended to have higher psychiatric morbidity. PMID- 1642610 TI - Bush psychiatric services. AB - This is a description of the psychiatric services at present provided to the Far West Region of New South Wales. On account of the isolation of the region, and noting that the area probably has a higher than normal rate of psychiatric and psycho-social morbidity, there are special problems involved in the provision of comprehensive treatment services. I am the only resident psychiatrist within the region, and work as both a Visiting Medical Officer to the Broken Hill Base Hospital, to Wilcannia Hospital, and to the Prison Medical Service, as well as half time in private practice. The Mental Health Services to the area are at present being considerably expanded, and in this paper their structure and function will be described, and the special problems of providing a comprehensive service to an isolated area of the bush will be discussed. The inequity of service allocation to the region will be highlighted. It is noted that the region's total share of the financial mental health cake has dropped by about 40% in the last ten years as a result of the setting up of local community services and dramatically reduced in-patient hospitalisation costs in Sydney and Adelaide. PMID- 1642611 TI - The Broken Hill Psychopathology Project. AB - The main objective of this study was to describe the psychiatric disorders seen in patients presenting for treatment in rural New South Wales. The patients were seen primarily in the community, in both public and private practice, but also in the local base hospital and prison. Seven hundred and seven patients were consecutively examined during the study period. The results of this study were compared with a previous Australia-wide study to identify specific disorders that were more prevalent in rural areas. Alcohol abuse and dependence stood out as being much more prevalent. Life problems such as domestic violence, sexual assault, and incest occurred commonly in women referred for psychiatric assessment. More than ten percent of the study patients were children aged under 17, who had similar prevalence rates of the various psychiatric disorders to a national comparison. It is concluded that alcohol abuse is very common in rural New South Wales, particularly in men, although there are also high rates in women, and this is probably related, in part at least, to the high rates of domestic violence, sexual assault and incest. It appears probable that there is a cycle of alcohol abuse in men leading to domestic violence and sexual abuse in women and children. This may contribute to the latter becoming anxious and depressed. The rates of the major functional psychiatric disorders were similar to those seen nationally. There is a great need for the maldistribution of psychiatrists between metropolitan and rural areas to be addressed. PMID- 1642612 TI - The relationship between risk factors for affective disorder and poststroke depression in hospitalised stroke patients. AB - The influence of psychiatric risk factors on the development of depression following stroke was examined in 88 patients undergoing inpatient rehabilitation. In this sample, 34 patients (38%) had a diagnosis of major or minor depression. Older age and a personal or family history of affective or anxiety disorder were associated significantly with major depression. Minor depression was more common among males and those patients with greater physical disability. Severity of depressive symptoms was associated with a personal or family history of affective or anxiety disorder and higher pre-stroke personality neuroticism. We conclude that certain psychiatric risk factors for affective disorder are strongly associated with poststroke depression. The implications of these findings for anticipating and managing poststroke depression are discussed. PMID- 1642613 TI - Psychiatric consultation in a spinal injuries unit. AB - The function of a consultation liaison service to a spinal injuries unit is described. Within this context, a study was conducted in which sociodemographic and clinical data were collected over a 4 year period for consecutive admissions to the unit. Data are presented for 227 patients admitted during this period. Forty-seven patients were found to have discrete psychiatric disorders (DSM III) which required treatment during the course of their inpatient care. For forty-two of these patients the psychiatric disorder first developed following spinal cord injury. PMID- 1642614 TI - The effect of computer-assisted interviewing on the clinical assessment of children. AB - This study investigated the effect of providing clinicians with a report from a computer-assisted interview conducted prior to the clinical assessment of children referred to a mental health service. The results suggest that the availability of reports from computer-assisted interviews influenced the type of problems identified by clinicians and the services that they recommended to manage the children's problems. It is suggested that reports from computer assisted interviews could assist clinicians by collecting a broad range of clinical information describing the problems of clinic-referred children. It is also suggested that considerably more research is needed into the possible benefits of computer technology in child and adolescent mental health services. PMID- 1642615 TI - Psychological adjustment of relinquishing mothers before and after reunion with their children. AB - A main objective of this study was to compare the emotional well-being of mothers who had already experienced a reunion with children relinquished two to four decades ago, with that of mothers who were still awaiting the possibility of such re-contact. A nationwide postal survey was carried out in New Zealand of the relinquishment experiences and subsequent adjustment of 238 women who had been able to re-contact their children and of 206 women who had not as yet made contact. The two subgroups did not differ on two standardised measures of psychological well-being (GHQ-28 and global self esteem). However, the post reunion women reported significantly greater improvements in their feelings connected with "adoption events", and also reported higher levels of perceived social support than did the pre-reunion women. Women who still lacked any information about their relinquished child showed significantly more negative affect and poorer psychological well-being than those who had at least obtained some non-identifying information. PMID- 1642616 TI - Immunological and psychological dysfunction in patients receiving immunotherapy for chronic fatigue syndrome. AB - Associations between immunological and psychological dysfunction in 33 patients with Chronic Fatigue Syndrome (CFS) were examined before and in response to treatment in a double blind, placebo-controlled trial of high dose intravenous immunoglobulin. Only those patients who received active immunotherapy demonstrated a consistent pattern of correlations between improvement in depressive symptoms and markers of cell-mediated immunity (CMI). This finding lends some support to the hypothesis that depressive symptoms in patients with CFS occur secondary to, or share a common pathophysiology with, immunological dysfunction. This pattern and the lack of strong associations between depression and immunological disturbance prior to treatment are less supportive of the view that CFS is primarily a form of depressive disorder or that immunological dysfunction in patients with CFS is secondary to concurrent depression. PMID- 1642617 TI - Predicting the outcome of schizophrenia ten years later. AB - A total of 407 new admissions to Woodbridge Hospital, Singapore in 1975 with a diagnosis of schizophrenia were examined 10 years later to determine which variables were predictive of outcome. Useful predictors were marital status, duration of illness and Feighner's diagnostic criteria. Fairly useful predictors were age, sex and educational status. Race, family history, suicidal behaviour, thought disorder, affective blunting, delusions and hallucinations were not useful for predicting long term prognosis. PMID- 1642618 TI - Looking beyond the 1:10,000 ratio of psychiatrists to population. AB - The frequently quoted ratio of 1:10,000 psychiatrists to population originated in Canada in 1962 and was later adopted as the minimum by the American Psychiatric Association. Since then both Canada and the United States have found this ratio to be inadequate. Canada has since advocated an optimal target ratio of 1:6,500, but recommended a more attainable pragmatic ratio of 1:8,000 for the foreseeable future. The Royal Australian and New Zealand College of Psychiatrists' recently recommended range of 1:7,500 to 1:10,000 is applauded. Reasons are given why a reasonable upper limit to the ratio of psychiatrists to population is desirable. PMID- 1642619 TI - Is mental disease just brain disease? The limits to biological psychiatry. AB - As a process of rational enquiry into an empirical field, psychiatry must submit itself to the same discipline as other areas of science. Effectively, it must show that its fundamental premises are both internally and externally consistent, and that its methods of investigation satisfy prevailing criteria of scientific methodology. When psychoanalytic psychology (and hence all psychodynamic models) and behaviourism were analysed from these points of view, they were found wanting. To date, there has been little or no meta-analysis of the third great school of psychiatric theorizing, biological psychiatry. A preliminary analysis establishes sharp limits to the notion that biological psychiatry is the "wave of the future". Like psychoanalysis and behaviourism, it cannot form the basis of a general theory of psychiatry. Since it lacks an adequate theoretical framework, the inescapable conclusion is that psychiatry is nothing more than protoscience. PMID- 1642620 TI - Encounter with neurophilosophy. PMID- 1642621 TI - Chance: a major factor in the causation of mental illness. AB - This paper questions the adequacy of traditional models of human behaviour, including models of functional mental illness. It is proposed that random (chance) variation is an invariable rule of nature which must apply to neurophysiological processes. Because of this, internal chance (random variation in neurophysiological processes) must be an important factor in determining the course and onset of mental illness. It is proposed that external chance- fortuitous changes in the complex pattern of interaction between physical and functional factors influencing behaviour--is also an important determinant of mental illness. It is proposed that many of the key characteristics of mental illness are explicable in terms of the properties of complex interactional systems. PMID- 1642622 TI - The quantum of meaning: an approach to the paradox of self-observation. AB - Self-observation contains a paradox largely unaddressed in current psychiatric theory. It is impossible to make "objective" observations of the meaning of our own thoughts and feelings because we use those very same thoughts and feelings to make our observations. Nevertheless most psychiatric theory assumes a clear separation between the internal part of ourselves which observes and that part which forms the object of our observations. Analogies from quantum physics can be used to elucidate this paradox. Once the complexities of self-observation are understood, so are many of the enigmas of psychotherapy. PMID- 1642623 TI - The evolution of community psychiatry. AB - Community Psychiatry is sometimes regarded as a separate and even as a recent study. The history of its evolution in Australia shows it to have resulted from a logical progression since the earliest days of the psychiatric services. The demand for care completely outstripped the accommodation available so two separate but parallel methods of dealing with this problem were evolved. The first explored how the numbers in the overcrowded hospitals could be reduced, and the second, the ways in which admission could be avoided. Both methods resulted in the expansion of community services. Present day activities must be viewed in this light and community services recognised to be an indivisible portion of a professionally organised total mental health organisation. PMID- 1642624 TI - Julius Wagner von Jauregg: a reappraisal. AB - A little more than half a century has passed since the death of Julius Wagner von Jauregg, a significant figure in the history of modern psychiatry. We believe that after this passage of time the life and work of Wagner von Jauregg deserve reappraisal. PMID- 1642625 TI - A history of the Lunatic Reception House, Darlinghurst. AB - The Lunatic Reception House at Darlinghurst operated between 1868 and 1961. Established to remove the stigma of criminality from the care of the insane, it operated as an observation ward and was for most of its time the sole portal of entry into metropolitan psychiatric hospitals in Sydney. An account of its inception and notable aspects of its history, with particular reference to lunacy legislation, is presented. PMID- 1642626 TI - Carbon monoxide, amnesia and hyperbaric oxygen therapy. AB - A case of carbon monoxide poisoning, initially misdiagnosed as conversion disorder, is presented. Cognitive deficits demonstrated at the time of psychiatric assessment were successfully reversed by hyperbaric oxygen therapy despite the 1 week delay. The clinical manifestations of carbon monoxide poisoning and the rationale for and timing of hyperbaric oxygen therapy are discussed. Emphasis is placed on the need for a high index of suspicion for carbon monoxide poisoning in the clinical situation of profound memory disturbance. PMID- 1642627 TI - Triazolam-induced nocturnal bingeing with amnesia. AB - A combination of behavioural and cognitive adverse effects is illustrated in this case report of a recurrent triazolam-induced eating disorder. The co-occurrence of bingeing, irritability and anterograde amnesia is suggestive of a drug-induced Kleine-Levin Syndrome. PMID- 1642628 TI - Sturge-Weber syndrome--a forgotten condition. PMID- 1642629 TI - The changing nature of psychiatry. PMID- 1642630 TI - The changing nature of psychiatry. PMID- 1642631 TI - Potentially reversible dementia. PMID- 1642632 TI - Monoamine oxidase inhibitors (MAOI) or reversible inhibitors of monoamine oxidase (RIMA)/tricyclic antidepressant (TCA) combination therapy. PMID- 1642633 TI - Chronic fatigue syndrome. PMID- 1642634 TI - Consent for ECT. PMID- 1642635 TI - Ethics and advertising. PMID- 1642636 TI - Psychiatrist-patient relationships. PMID- 1642637 TI - Quinone-induced DNA single strand breaks in rat hepatocytes and human chronic myelogenous leukaemic K562 cells. AB - In rat hepatocytes exposed to the quinones menadione and 2,3-dimethoxy-1,4 naphthoquinone (2,3-diOMe-1,4-NQ) a decrease in NAD+ is observed. DNA damage and activation of poly(ADP-ribose)polymerase are often associated with a decrease in NAD+. Using rat hepatocytes and human myeloid leukaemic cells (K562), we examined the extent of DNA damage induced by these quinones at non-toxic concentrations, i.e. at concentrations at which the cells completely exclude the dye trypan blue. Both quinones caused significant DNA damage at very low concentrations (5-100 microM). With 2,3-diOME-1,4-NQ (15 microM) or menadione (15 microM) single strand breaks (SSB) were observed at very early time points (less than 5 min), reaching a maximum between 20 and 30 min. Most SSB were repaired within 45 min of the removal of the quinones. Whilst extensive repair was observed within 4 hr of the removal of 2,3-diOMe-1,4-NQ (15 microM), only partial repair was observed following exposure to menadione (15 microM). SSB induced by 2,3-diOMe-1,4-NQ (15 microM) were completely inhibited by the iron chelator 1,10-phenanthroline (25 microM), whereas in cells exposed to menadione (15 microM) they were only partially inhibited. Finally, although the membrane integrity of K562 cells was unaffected by exposure to high concentrations of both quinones (less than or equal to 400 microM), cytostasis was observed at much lower concentrations (50 microM). Our results demonstrate that at very low concentrations these quinones induce extensive DNA damage possibly caused by hydroxyl radicals. The DNA damage was accompanied by an early cytostasis but no loss of membrane integrity. PMID- 1642638 TI - Studies on the biochemical effects of the aldose reductase inhibitor 2,7 difluorospirofluorene-9,5'-imidazolidine-2',4'-dione (Al 1576, HOE 843). Detection of D-glucaric and D-glucuronic acid excretion by high resolution 1H and 13C NMR spectroscopy. AB - The effects of two aldose reductase inhibitors on the biochemical composition of rat urine were investigated using high resolution 1H and 13C NMR spectroscopy. We report the elevated excretion of D-glucaric acid (DGA) and D-glucuronic acid (GCA) following treatment with 2,7-difluorospirofluorene-9,5'-imidazolidine-2'4' dione (Imirestat, IM, Al 1576, HOE 843) at 50 mg/kg/day for 1 month, but not with 3-4-bromo-2-fluorobenzyl-4-oxo-3-phthalazine-1-ylacetic acid (Ponalrestat, Statil), dosed at 50 mg/kg/day for 2 weeks. Sugar aciduria was also detected following treatment with the cytochrome P450 inducer phenobarbitone (PB) at 45 mg/kg/day for 1 month, although the qualitative and quantitative pattern of excretion of sugar acids differed greatly between the IM and PB treatment groups. The levels of GCA excreted are elevated 11-fold by IM treatment from 19.0 to 210.0 mumol/24 hr, but only 2.5-fold by PB, from 9.7 to 23.9 mumol/24 hr. DGA was not detectable in control urine, although levels did increase by 30% during the study from 7.5 to 10.9 mumol/24 hr, between day 8 and day 29, with IM treatment, and by 60% from 1.7 to 4.9 mumol/24 hr following PB administration for the same time period. This predominant elevation of DGA and GCA caused by IM treatment far exceeds previous records. In contrast, PB treatment resulted in an increase in intensity of a number of partially resolved sugar resonances, but at a much lower level than resulted from IM treatment. A raised level of DGA and GCA is usually associated with hepatic P450 induction; however, we report here profound DGA and GCA uria as a result of the inhibition of the aldehyde reductase, hexonate dehydrogenase (EC 1.1.1.19, EC 1.1.1.20). This mechanism is not closely linked to P450 induction, corroborating the current view that elevated excretion of DGA is not a reliable indicator of hepatic enzyme induction. This study further demonstrates the use of high resolution NMR spectroscopy in the detection of a novel biochemical effect which may go unnoticed during routine clinical chemistry tests. PMID- 1642639 TI - Inhibition of Trichomonas vaginalis ornithine decarboxylase by amino acid analogs. AB - Ornithine decarboxylase (ODC) from Trichomonas vaginalis was inhibited irreversibly by several substrate analogs. Of these, DL-alpha monofluoromethyldehydroornithine (MFMDO) and DL-alpha-monofluoromethylornithine (MFMO) were the most potent. The enzyme was unaffected by putrescine analogs suggesting that differences exist between the regulation of the trichomonad enzyme and that in other eukaryotes. In culture the ornithine analogs strongly inhibited putrescine synthesis and increased the generation time after 24 hr of exposure. In a semi-defined growth medium MFMDO methyl and ethyl esters increased the generation time from 4.5 hr to 9.0 and 8.2 hr, respectively. In standard undefined growth medium the trichomonad ODC was fully induced only after 15 hr (late log) and had an extended half-life of greater than 8 hr. PMID- 1642640 TI - The role of cytochrome P450 and cytochrome P450 reductase in the reductive bioactivation of the novel benzotriazine di-N-oxide hypoxic cytotoxin 3-amino 1,2,4-benzotriazine-1,4-dioxide (SR 4233, WIN 59075) by mouse liver. AB - SR 4233 or WIN 59075 (3-amino-1,2,4-benzotriazine-1,4-dioxide) is a novel and highly selective hypoxic cell cytotoxin requiring reductive bioactivation for its impressive antitumour effects. Expression of appropriate reductases will contribute to therapeutic selectivity. Here we provide more detailed information on the role of cytochrome P450 and cytochrome P450 reductase in SR 4233 reduction by mouse liver microsomes. Reduction of SR 4233 to the mono-N-oxide SR 4317 (3 amino-1,2,4-benzotriazine-1-oxide) is NADPH, enzyme and hypoxia dependent. An inhibitory antibody to cytochrome P450 reductase decreased the microsomal SR 4233 reduction rate by around 20%. Moreover, studies with purified rat cytochrome P450 reductase showed unequivocally that this enzyme was able to catalyse SR 4233 reduction at a rate of 20-30% of that for microsomes with equivalent P450 reductase activity. Exposure to the specific cytochrome P450 inhibitor carbon monoxide (CO) inhibited microsomal reduction by around 70% and CO plus reductase antibody blocked essentially all activity. Additional confirmation of cytochrome P450 involvement was provided by the use of other P450 ligands: beta diethylaminoethyl diphenylpropylacetate hydrochloride gave a slight stimulation while aminopyrine, n-octylamine and 2,4-dichloro-6-phenylphenoxyethylamine were inhibitory. Induction of SR 4233 reduction was seen with phenobarbitone, pregnenalone-16-alpha-carbonitrile and beta-napthoflavone, suggesting that cytochrome P450 subfamilies IIB, IIC and IIIA may be involved. Since cytochrome P450 and P450 reductase catalyse roughly 70 and 30%, of mouse liver microsomal SR 4233 reduction respectively, we propose that expression of these and other reductases in normal and tumour tissue is likely to be a major factor governing the toxicity and antitumour activity of the drug. PMID- 1642642 TI - Inactivation of brain cortex muscarinic receptors by 4-diphenylacetoxy-1-(2 chloroethyl) piperidine mustard. AB - We demonstrated in this study that 4-DAMP [4-diphenylacetoxy-1-(2- chloroethyl) piperidine] mustard, which cyclizes to the aziridinium ion, behaved as a non selective, non-competitive inhibitor of muscarinic receptors in rat brain cortex. It inactivated to the same extent the M1, M2 and M4 muscarinic receptors present in this tissue, as well as receptors accessible or not accessible to quaternary antimuscarinic drugs. Under mild incubation conditions, the muscarinic receptors in a state with super high affinity for agonists (SH receptors) were less affected by preactivated 4-DAMP mustard than the receptors in the states with lower affinity for agonists (H and L receptors). PMID- 1642641 TI - Effect of age and gender on the activity of human hepatic CYP3A. AB - Many pharmacokinetic investigations in the elderly population reveal decreased clearance of lipophilic drugs metabolized by the cytochrome P450 enzymes; however, few studies have evaluated aging-dependent or gender-related changes in specific cytochrome P450 enzymes. The clearance of quinidine, midazolam, triazolam, erythromycin, and lidocaine declines with age; these drugs are metabolized by the isoform, CYP3A. To determine whether these metabolic effects are due to changes in CYP3A, the effects of age and gender on CYP3A activity were examined. The activity of the human hepatic cytochrome P450, CYP3A, was quantified in vitro as erythromycin N-demethylation in microsomes prepared from forty-three resected human liver specimens obtained from patients, age 27 to 83, with normal liver function. Erythromycin N-demethylation varied 5-fold in human liver microsomes. CYP3A activity was 24% higher in females than males (P = 0.027). CYP3A activity did not correlate with age, smoking status, ethanol consumption or percent ideal body weight. Large interindividual differences and a small female-specific increase in CYP3A activity were obtained. However, CYP3A activity was unaffected by age over the range of 27-83 years, suggesting that the aging-related alteration in the clearance of CYP3A substrates is secondary to changes in liver blood flow, size, or drug binding and distribution with aging. PMID- 1642643 TI - Stereoselective interactions of ketoprofen glucuronides with human plasma protein and serum albumin. AB - A clearance pathway common to many aryl alkanoic acids is the generation of renally eliminated ester glucuronides. These metabolites are susceptible to systemic hydrolysis which generates the parent aglycone. We have conducted in vitro studies with biosynthetic R- and S-ketoprofen glucuronides to elucidate the mechanism of this phenomenon. These conjugates were incubated in human plasma, various concentrations of human serum albumin (HSA) and protein-free buffer. It was apparent that albumin, rather than plasma esterases, catalysed the hydrolysis of the glucuronides. The albumin-catalysed hydrolysis of ketoprofen glucuronides was highly stereoselective. The mean (+/- SD) hydrolysis half-life of R ketoprofen glucuronide in plasma (N = 4) at physiological pH and temperature was 1.37 (+/- 0.30) hr. The corresponding value for S-ketoprofen glucuronide, 3.46 (+/- 0.84) hr, was significantly different (P less than 0.005). In contrast, synthetic ethyl esters of R- and S-ketoprofen were hydrolysed by plasma esterases, but not by HSA, and with little stereoselectivity. The reversible protein binding of ketoprofen glucuronides was determined at physiological pH and temperature by a rapid ultra-filtration method. The binding of R- and S ketoprofen glucuronide to human plasma protein was independent of concentration (P greater than 0.05) over the range of 1-20 micrograms/mL. The mean (+/- SD) percentage unbound in plasma (N = 4) of R-ketoprofen glucuronide was 12.6 (+/- 1.4)%. The corresponding value for S-ketoprofen glucuronide, 9.12 (+/- 0.54)%, was significantly different (P less than 0.005). S-Ketoprofen glucuronide was also more avidly protein bound in physiological concentrations of HSA. However, this stereoselectivity decreased in more dilute HSA solutions. Based on the hydrolysis and protein binding data for ketoprofen glucuronides, we propose the existence of separate binding and catalytic sites on the albumin molecule for these metabolites. PMID- 1642644 TI - Effect of depolarizing agents on the Ca(2+)-independent and Ca(2+)-dependent release of [3H]GABA from sheep brain synaptosomes. AB - The purpose of the present study was to compare the effects of several depolarizing agents on both the membrane potential and on the release of [3H] gamma-aminobutyric acid (GABA) from sheep brain cortex synaptosomes. We examined the effects of KCl, 4-aminopyridine (4-AP), veratridine, ouabain and tetraphenylphosphonium cation (TPP+) on Ca(2+)-independent (carrier-mediated) and Ca(2+)-dependent (exocytotic) release. We found that, in the absence of Ca2+, KCl at 40 mM releases 7.57 +/- 0.65%, veratridine at 50 microM releases 45.85 +/- 2.48%, ouabain at 1 mM releases 8.62 +/- 0.93% and TPP+ at 1 mM releases 4.09 +/- 0.37% of the total accumulated neurotransmitter, provided that the external medium contains Na+. These are about the maximal values of release obtained with each depolarizing agent in a Na+ medium and in the absence of Ca2+. Replacing external Na+ with choline blocks the release observed in the presence of the depolarizing agents in the absence of Ca2+, and this divalent ion can increase [3H]GABA release only for K+ or 4-AP. Synaptosomal depolarization requires Na+ except for K+ depolarization. Furthermore, although Ca2+ stimulates the release of [3H]GABA due to K+ depolarization (13.56 +/- 0.44%) or due to 4-AP (4.26 +/- 0.51%), it inhibits the release due to the other depolarizing agents. The amount of [3H]GABA released by 4-AP in Na+ medium (4.26 +/- 0.51%) is similar to that induced by KCl in the presence of Ca2+ in the absence of Na+ (3.39 +/- 0.29%) which represents only exocytotic release. This suggests that the Ca(2+)-dependent exocytotic release of [3H]GABA can be specifically induced by 4-AP in a Na+ medium, or by KCl in the absence of Na+, as reported by us earlier. The observation that Ca2+ inhibits the Ca(2+)-independent release is of interest because it suggests that Ca2+ may modulate the release of cytoplasmic GABA probably by inhibiting the carrier-mediated release of GABA. It is of interest as to whether Ca2+ regulation depends on intracellular Ca2+. PMID- 1642645 TI - Characterization of cryopreserved rat liver parenchymal cells by metabolism of diagnostic substrates and activities of related enzymes. AB - The metabolism of testosterone and benzo(a)pyrene (BaP) which is mediated by diverse enzymes was determined in cryopreserved rat liver parenchymal cells and compared with that found in freshly isolated cells. In addition, the activities of single xenobiotic-metabolizing enzymes were measured by using specific substrates. The cytochrome P450 (P450)-mediated total metabolic conversion of testosterone was reduced to 55% in cryopreserved cells. The metabolite profile, i.e. the formation of single metabolites compared with total metabolic conversion, was however unchanged when compared with freshly isolated cells. A concomitant reduction in the activities of the involved P450 isoenzymes can therefore be postulated. The amount of detected phase I-metabolites of BaP was unaffected by the cryopreservation method. The formation of phase II-metabolites and total metabolic conversion of BaP in cryopreserved cells was however reduced to about 50-60%. The reduced glutathione S-transferase and more obviously phenol sulfotransferase activities measured in cryopreserved cells, may explain the impaired conjugation of BaP. The ratio between phase I- and phase II-metabolites was thus changed by cryopreservation. Density separation on Percoll yielded cryopreserved cells with a viability and metabolic capacity not measurably different from freshly isolated cells. To this extent, cryopreserved, Percoll purified liver parenchymal cells are a useful in vitro system for drug metabolism studies. However due to the extensive loss in cell number during this procedure (recovery = 22% of freshly isolated cells) the application of this system is limited. PMID- 1642646 TI - Schizophrenic patients treated with high dose phenothiazine or thioxanthene become deficient in polyunsaturated fatty acids in their thrombocytes. AB - Total fatty acids were analysed in thrombocytes of schizophrenic patients treated with a "high dose" or "low dose" monotherapy of neuroleptic drugs phenothiazine or thioxanthene. The ratio of the very long chain fatty acid hexacosanoic acid to the long chain fatty acid docosanoic acid (C26:0/C22:0) increased in the "high dose" and "low dose" groups as compared to healthy untreated controls (P less than 0.05). The polyunsaturated fatty acid arachidonic acid decreased in the "high" and "low dose" groups (P less than 0.01 and P less than 0.05). The polyunsaturated fatty acids alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid were not detectable in most of the "high dose" schizophrenic patients, however, they were found in the "low dose" group and in the controls. There was a negative correlation between the daily dosage of phenothiazine and the percentages of the polyunsaturated fatty acids arachidonic acid and alpha linolenic acid+eicosapentaenoic acid+docosahexaenoic acid in thrombocytes (r = 0.87, P less than 0.01 and r = -0.81, P less than 0.01). Two patients of the "high dose" group with an especially high and long lasting monotherapy of neuroleptics were nearly devoid of polyunsaturated fatty acids in their thrombocytes. Untreated schizophrenic patients exhibited a fatty acid pattern in their thrombocytes not markedly different from that of the healthy untreated control group. We conclude that neuroleptic drugs phenothiazine or thioxanthene can alter the fatty acid pattern of thrombocytes. PMID- 1642647 TI - Effect of dietary lipids on levels of UDP-glucuronosyltransferase in liver. AB - Others have shown recently that dietary fish oil protects against acetaminophen induced liver injury in vivo. Fish oil was protective because it increased the clearance of acetaminophen via glucuronidation. This work left unresolved the basis for increased rates of glucuronidation in animals fed fish oil. We therefore have determined how the amount and type of lipid in the diet affect the activity of liver microsomal UDP-glucuronosyltransferase activity. Male Wistar rats were fed a fat-free diet or isocaloric diets containing 5% corn oil, olive oil or fish oil for 4 weeks. The activity of UDP-glucuronosyltransferase was highest in rats fed fish oil and lowest in rats fed the fat-free diet. Treatment with corn oil and olive oil resulted in intermediate levels of activity. Diet induced differences in amounts of UDP-glucuronosyltransferase were shown by immunoblotting and kinetic measurements. Treatment with fish oil resulted in a 3 fold increase in the amount of UDP-glucuronosyltransferase versus the fat-free diet. Corn oil and olive oil diets caused 2-fold increases in the amount of UDP glucuronosyltransferase versus the fat-free diet. Fatty acid analysis of microsomal lipids showed that the fat-free diet was associated with decreased levels of arachidonic acid versus the corn oil or olive oil diets. The fish oil diet resulted in increased levels of omega-3 fatty acids versus the other diets. PMID- 1642649 TI - Acute effect of benfluorex on glucose metabolism. AB - The antihyperlipidaemic agent benfluorex [1-(3-trifluoromethylphenyl)-2-(2 benzoyl-oxyethyl)-aminopropane] and its metabolite S422 [1-(3 trifluoromethylphenyl)-2-(2-hydroxyethyl)-aminopropane] were examined for an acute (after 1-2 hr) effect on glucose metabolism in normal rats. Enteral administration of benfluorex (25 mg/kg) did not affect basal plasma glucose and insulin concentrations. However, enteral and intravenous glucose tolerance were modestly improved without enhancing the insulin response to glucose. Hepatic gluconeogenesis from lactate was not acutely altered by benfluorex (25 mg/kg) in vivo or by S422 (1 mM) in vitro, but S422 (1 mM) slightly reduced (by 11%) hepatic glycogen mobilization in vitro after 2 hr. S422 (1 mM) increased (by 47%) glucose oxidation by diaphragm muscle in vitro. The effect was additive to that of insulin. Anaerobic glucose metabolism and glycogenesis of diaphragm muscle were not affected by S422. The results suggest that benfluorex can acutely improve glucose tolerance associated with increased glucose oxidation by muscle. PMID- 1642648 TI - Quinone reduction and redox cycling catalysed by purified rat liver dihydrodiol/3 alpha-hydroxysteroid dehydrogenase. AB - A highly active preparation of rat liver dihydrodiol/3 alpha-hydroxysteroid dehydrogenase was obtained using a newly developed, rapid purification scheme involving affinity chromatography on Red Sepharose. Depending on the coenzyme present, the purified enzyme was found to catalyse the oxidation of dihydrodiols and steroids or the reduction of substrates with carbonyl or quinone moieties. Using a wide range of synthetic quinones derived from polycyclic aromatic hydrocarbons (PAHs), we observed a pronounced regioselectivity of the quinone reductase activity. Good substrates were the o-quinones of phenanthrene, benz(a)anthracene, chrysene and benzo(a)pyrene with the quinonoid moiety in the K region which were reduced at rates of 1-10 mumol/min.mg enzyme. 1,4-Benzoquinone, naphthalene-1,2-quinone and benz(a)anthracene-8,9-quinone were also reduced at high rates. In contrast, alkyl-substituted quinones such as duroquinone and menadione were poor substrates for the enzyme. During the enzymatic reduction of several o-quinones, but not 1,4-benzoquinone, we observed the oxidation of large amounts of NADPH and the consumption of molecular oxygen which is indicative of a redox-cycling process. Thus, the reduction of quinones of PAHs may lead to a facilitated conjugation and excretion of these highly lipophilic compounds, but may also initiate toxic processes due to the formation of reactive oxygen species. PMID- 1642650 TI - The influence of ebselen on the toxicity of cisplatin in LLC-PK1 cells. AB - LLC-PK1 cells have been used as an in vitro model to study the nephrotoxicity of the antitumor drug cisplatin. A concentration-dependent cytotoxicity of cisplatin, measured as lactate dehydrogenase leakage and amount of protein remaining attached to the culture plate, was observed. At a cisplatin concentration of 0.4 mM cell viability was reduced to 21% after 72 hr. Ebselen, a seleno-organic compound capable of forming selenol intermediates through reaction with thiols, was found to protect LLC-PK1 cells against cisplatin-induced toxicity at low concentrations (5-15 microM). The ebselen-induced protection against cisplatin toxicity in this in vitro test system apparently correlates well with a similar protection previously observed in vivo in mice and rats. PMID- 1642651 TI - Reduced drug accumulation in a newly established human lung squamous-carcinoma cell line resistant to cis-diamminedichloroplatinum(II). AB - A human lung squamous-carcinoma cell line resistant to cis diamminedichloroplatinum(II) (CDDP), designated PC10-B3, has been established from the original cell line PC10 by a stepwise increment of the CDDP concentration. This is the first report, to our knowledge, to establish a CDDP resistant lung squamous-carcinoma cell line. PC10-B3 has continued to proliferate in the presence of 0.5 micrograms/mL CDDP, whereas PC10 could not survive. A 3 (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that PC10-B3 was 11.4-fold more resistant to CDDP than PC10 and cross-resistant to diammine(1,1-cyclobutanecarboxylate)platinum(II) (CBDCA) and 254-S, but not to doxorubicin or etoposide. PC10-B3 was characterized by a smaller DNA index and a larger cell size compared to PC10. The level of intracellular platinum accumulation was reduced by about 5- to 8-fold in PC10-B3 when compared with PC10, suggesting that reduced drug accumulation may be one of the important factors in contributing to CDDP resistance in PC10-B3. PMID- 1642652 TI - Comparison of azathioprine, methotrexate, and the combination of both in the treatment of rheumatoid arthritis. A controlled clinical trial. AB - OBJECTIVE: To compare the relative safety and efficacy of azathioprine (AZA), methotrexate (MTX), and the combination of both in the treatment of active rheumatoid arthritis (RA). METHODS: Two hundred twelve patients with active RA were entered into a 24-week prospective, controlled, double-blind, multicenter trial and were randomly assigned to 1 of 3 treatment groups. RESULTS: One hundred fifty-eight patients finished 24 weeks of the study. There were no remissions seen but response rates were greater than 30% for all outcome measures. Combination therapy was not statistically superior to MTX therapy alone, but both combination therapy and MTX alone were superior to AZA alone when patients were analyzed by intent-to-treat and with withdrawals treated as therapy failures. If only patients who continued taking the therapy were analyzed, the mean improvement was greater for AZA therapy than for MTX, while the combination remained the most active. Adverse effects on the gastrointestinal tract and elevations of liver enzyme levels were the most frequent causes for discontinuations. CONCLUSION: Both combination therapy and MTX alone were superior to therapy with AZA alone for active RA but were not statistically different in their effect on outcome assessment. PMID- 1642653 TI - Effect of gold compounds on the activity of adenylyl cyclase in human lymphocyte membranes. AB - OBJECTIVE: To determine the effects of aurothioglucose, aurothiomalate, and auranofin on basal and forskolin-activated adenylyl cyclase activity in human total lymphocyte membranes, and in membranes of T and B lymphocyte subsets. METHODS: Membranes were isolated from human total lymphocytes and T and B cell subsets. The effects of gold compounds on basal and forskolin-stimulated activity of adenylyl cyclase were measured by radioassay. RESULTS: The gold compounds inhibited adenylyl cyclase activity. This inhibitory effect required the presence of both the sulfhydryl ligands and aurous cation. CONCLUSION: Regulation of lymphocyte adenylyl cyclase by gold compounds represents a potential mode of action of these drugs in rheumatic diseases. PMID- 1642654 TI - Inhibition of the production of proinflammatory cytokines and immunoglobulins by interleukin-4 in an ex vivo model of rheumatoid synovitis. AB - OBJECTIVE: To assess the spontaneous production of proinflammatory cytokines and immunoglobulins in rheumatoid arthritis (RA) synovitis and modulation by interleukin-4 (IL-4). METHODS: We developed an ex vivo model of RA synovitis using pieces of RA synovium, and have studied the regulation of the production of IL-1 beta, IL-6, tumor necrosis factor alpha (TNF alpha), IgM, and IgG. RESULTS: Spontaneous production of proinflammatory cytokines in vitro was active, with prolonged cytokine gene transcription and translation. IL-6 was produced at higher levels than either IL-1 beta or TNF alpha, and explants produced more IgG than IgM. In contrast, IL-4 and interferon-gamma were undetectable. When pieces of synovium were incubated in the presence of IL-4, reduction of spontaneous proinflammatory cytokine and Ig production was observed. CONCLUSION: These results extend the observations of the antiinflammatory properties of IL-4 to an ex vivo situation, and provide the rationale for the clinical use of IL-4 in RA. PMID- 1642655 TI - Autoradiographic localization and analysis of endothelin-1 binding sites in human synovial tissue. AB - OBJECTIVE: To determine the localization of endothelin binding sites and immunoreactivity in human synovial tissues. METHODS: Quantitative in vitro autoradiographic and immunohistochemical techniques were used to localize and characterize 125I-labeled endothelin-1 (125I-ET-1) binding sites and endothelin like immunoreactivity in sections of rheumatoid, osteoarthritic, and normal synovium. RESULTS: Specific 125I-ET-1-binding sites, characteristic of the ETA receptor, were localized to the media of synovial blood vessels in all 3 groups. No difference was found in vascular binding site density in rheumatoid and osteoarthritic synovium. Endothelin-like immunoreactivity was localized to endothelial cells in blood vessels displaying 125I-ET-1 binding sites. CONCLUSION: We conclude that endothelin may act locally, modulating synovial perfusion and exacerbating hypoxia in chronic arthritis. PMID- 1642656 TI - The immunoglobulin kappa light chain repertoire expressed in the synovium of a patient with rheumatoid arthritis. AB - OBJECTIVE: To analyze the nature of the B cell response in the synovial tissue of a patient with rheumatoid arthritis (RA). Specifically, we sought to determine if the pattern of immunoglobulin expression was consistent with polyclonal stimulation of B cells or an antigen-driven response. METHODS: We generated an unrestricted complementary DNA (cDNA) library from the diseased synovium of a rheumatoid factor (RF)-positive patient with an 18-year history of RA. A random sample of kappa light chain recombinants was identified, and sequence analysis was performed. The variable domains were compared with an extensive database of germline and cDNA kappa sequences. RESULTS: We found a light chain repertoire enriched for kappa transcripts containing 2 V kappa gene segments (Humkv325 and Humkv328) that are frequently associated with paraproteins expressing RF activity. Kappa variable domains from synovium contained numerous somatic mutations which resulted in frequent replacement of amino acids that encode the classic antigen-binding site. Unexpectedly, many of these kappa transcripts contained non-germline-encoded nucleotides (N regions) at the site of V kappa-J kappa joining. The combination of N-region addition and variation in the sites of V kappa-J kappa splicing generated unusually long complementarity-determining region 3 regions and charged amino acids near the V kappa-J kappa splice site. CONCLUSION: The pattern of somatic mutations found in this patient sample supports the hypothesis that these synovium-derived plasma cells are the product of immunoglobulin receptor-dependent (i.e., antigen-driven) selection. The extent of N-region addition raised the additional possibility that these antibodies derive from an unusual set of B lymphocytes that have escaped normal regulation. PMID- 1642657 TI - Utility of high-resolution ultrasound for the diagnosis of dialysis-related amyloidosis. AB - OBJECTIVE: To evaluate the utility of real-time, high-resolution ultrasound of the shoulder in the diagnosis of dialysis-related amyloidosis. METHODS: We performed a case series study of 2 groups of patients seen at a referral-based clinic in a tertiary care hospital. The shoulders of 13 patients with normal renal function and of 38 patients receiving long-term hemodialysis were studied by real-time, high-resolution ultrasound. All hemodialysis patients were evaluated clinically for the presence of dialysis-related amyloidosis. Surgical specimens of joints were available for all 13 patients with normal renal function and for 17 of the 38 hemodialysis patients. These specimens were evaluated for the presence of beta 2-microglobulin (beta 2m) amyloid by Congo red and immunohistochemical staining. RESULTS: Two ultrasonographic findings were selectively observed in the dialysis patients with clinical and histologic evidence of beta 2m amyloid in comparison with patients with normal renal function and no evidence of amyloid: rotator cuffs greater than 8 mm in thickness and echogenic pads between muscle groups of the rotator cuff. The presence of at least 1 of these 2 findings corresponded to the presence of clinically and histologically evident beta 2m amyloid with a sensitivity of 79% and a specificity of 100%. When additional patients without surgical specimens for histologic confirmation of amyloidosis were included, the sensitivity of these 2 sonographic findings was 72% and the specificity was 97%. CONCLUSION: Real-time, high-resolution ultrasound is a relatively sensitive and highly specific noninvasive adjunct to the clinical diagnosis of beta 2m amyloidosis in patients receiving long-term hemodialysis. PMID- 1642658 TI - Mast cell changes in scleroderma. Presence of MCT cells in the skin and evidence of mast cell activation. AB - OBJECTIVE: To analyze the concentration and distribution of the MCT (tryptase positive, chymase-negative) and MCTC (tryptase-positive, chymase-positive) types of mast cell in cutaneous lesions of scleroderma. METHODS: Biopsy specimens were obtained from skin lesions in 24 patients with scleroderma, and subjected to double immunohistochemical analysis using mouse monoclonal anti-tryptase and anti chymase antibodies. RESULTS: Dermal mast cell concentrations were below the normal range in 12 of the specimens, most of which were obtained between 1 and 4 years after disease onset. All other specimens contained normal concentrations of mast cells. MCT cells were present in 12 specimens and comprised between 8% and 100% of the total mast cells. Extracellular tissue deposits of tryptase-positive and/or chymase-positive granular material were observed in 8 specimens, suggesting possible mast cell degranulation. CONCLUSION: These findings are in contrast to those in normal skin, where MCTC cells are essentially the only type of mast cell present in the dermis. The results suggest that mast cells are involved in the pathogenesis of cutaneous lesions in scleroderma. PMID- 1642659 TI - Anti-interleukin-6 autoantibodies in rheumatic diseases. Increased frequency in the sera of patients with systemic sclerosis. AB - OBJECTIVE: To investigate the presence and the roles of anti-interleukin-6 (anti IL-6) autoantibodies in rheumatic diseases, and to further elucidate clinical and pathophysiologic significance of anticytokine autoantibodies. METHODS: Anti-IL-6 IgG autoantibodies were measured by the 125I-IL-6 binding activity of IgG, which was isolated from serum by protein A-Sepharose. RESULTS: Nine of 52 sera (17.3%) from patients with systemic sclerosis (SSc) contained anti-IL-6 antibodies, whereas only 1.9% of sera from normal subjects and 0-5% of sera from patients with other rheumatic diseases were positive for the antibodies. Moreover, anti-IL 6 autoantibodies were found predominantly among patients with the limited form of SSc (42.9%), compared with those with the diffuse form (7.9%). CONCLUSION: Anti IL-6 IgG autoantibodies were detected in patients with SSc, particularly those with the limited form of the disease, at a significantly increased frequency compared with normal subjects and patients with other rheumatic diseases. These results suggest that the development of anti-IL-6 autoantibodies and IL-6 may have a role in the pathophysiology of SSc. PMID- 1642660 TI - Fluorescent light photosensitivity in patients with systemic lupus erythematosus. AB - OBJECTIVE: To determine the prevalence of fluorescent light toxicity in patients with systemic lupus erythematosus (SLE). METHODS: SLE patients were polled about their symptomatic responses to sunlight and cool white fluorescent light. Photometry was used to determine the levels of ultraviolet (UV) emissions from fluorescent lamps. RESULTS: Thirteen of 30 photosensitive SLE patients described increases in disease activity following exposure to unshielded fluorescent lamps. Photometry indicated that these lamps emit substantial levels of UV-B (280-320 nm) radiation, which is toxic to patients with SLE. Standard acrylic diffusers absorbed this radiation, and their use was associated with almost no patient reported problems. CONCLUSION: Fluorescent lamps, emitting UV-B radiation, induce disease activity in photosensitive SLE patients. Standard acrylic diffusers absorb UV-B radiation and appear to be protective against induction of disease activity with the use of fluorescent lamps. PMID- 1642661 TI - Anti-Ro/SS-A and anti-La/SS-B autoantibody levels in relation to systemic lupus erythematosus disease activity and congenital heart block. A longitudinal study comprising two consecutive pregnancies in a patient with systemic lupus erythematosus. AB - OBJECTIVE: To analyze the anti-Ro/SS-A and anti-La/SS-B autoantibody responses, both quantitatively and qualitatively, in relation to the occurrence of congenital heart block (CHB) and disease activity in a patient with systemic lupus erythematosus. METHODS: The patient's course was carefully documented for a period of 80 months. Specific enzyme-linked immunosorbent assays, a HeLa cell immunoblotting test, and an RNA precipitation assay were used to determine autoantibody levels and fine specificities. RESULTS: Anti-Ro/SS-A and anti-La/SS B antibody did not disappear. Levels of anti-Ro/SS-A appeared to fluctuate more frequently than levels of anti-La/SS-B. Fluctuations were unrelated to disease activity or immunosuppressive treatment. There was no characteristic relationship between levels of these antibodies and the occurrence of CHB. CONCLUSION: The occurrence of CHB cannot be predicted by frequent measurement of anti-Ro/SS-A and anti-La/SS-B levels. The immunoregulatory control of anti-Ro/SS-A and anti-La/SS B antibodies differs from that of anti-DNA and anti-tetanus toxoid antibodies. PMID- 1642662 TI - Evaluation of the efficacy and safety of oral tiludronate in Paget's disease of bone. A double-blind, multiple-dosage, placebo-controlled study. AB - OBJECTIVE: To assess the optimal dosage of oral tiludronate in Paget's disease of bone. METHODS: We studied 149 patients with Paget's disease, in a double-blind, randomized, placebo-controlled trial. Patients were randomly assigned to 1 of 5 therapeutic groups: a daily dose of 100 mg, 200 mg, 400 mg, or 800 mg of oral tiludronate, or a placebo. Treatment was for 3 months, followed by 3 months of placebo-controlled followup. Serum alkaline phosphatase activity (SAP) and fasting urinary excretion of hydroxyproline/creatinine (OH/Cr) were measured monthly, as were biochemical parameters reflecting renal, hepatic, and hematologic functions. Analgesic efficacy was self-evaluated from a visual analog scale and a global pain index. RESULTS: Statistical analysis revealed that beginning at a dosage of 200 mg/day, there was a direct dose-dependent effect on the reduction of SAP and OH/Cr levels. Reduction of SAP levels was clinically significant at a dosage of 400 mg (44.9 +/- 4.2% reduction at 90 days and 49.2 +/ 4.5% at 180 days, mean +/- SEM) and at 800 mg (53.4 +/- 5% at 90 days and 59.3 +/- 4.6% at 180 days). There was a significant reduction in pain in all groups, including the group taking placebo. In only those taking 800 mg/day of tiludronate was there a significant frequency of complete resolution of pain (versus placebo). Aside from mild gastrointestinal disturbances, as experienced with other oral bisphosphonates, clinical tolerance of all 5 regimens was good. Exhaustive biochemical investigations failed to reveal significant toxicity of tiludronate up to the 800-mg daily dose investigated. CONCLUSION: Because of its significantly better antiresorptive effects and greater analgesic properties (compared with lower dosages), combined with the excellent clinical and biochemical tolerance, the 800-mg daily dose of tiludronate appears to be optimal for the treatment of Paget's disease of bone. PMID- 1642663 TI - Selective inhibition of granulopoiesis with severe neutropenia in systemic lupus erythematosus. PMID- 1642664 TI - C-reactive protein levels as a direct indicator of interleukin-6 levels in humans in vivo. PMID- 1642665 TI - Increase of survival time in experimental hypoxia by cytidine diphosphate choline. AB - 36 Wistar rats were kept in chronic hypoxic hypoxia of 7 vol % of oxygen in 2 experiments over a period of 6 months, other 36 served as controls. Half of the animals of each group received cytidine diphosphate choline (CDP-choline, citicoline, Somazina; CAS 987-78-0) at a dose of 100 mg/kg body weight in the liquid food. Animals in chronic hypoxia without application of CDP-choline developed pathological symptoms and began to die after 19 to 23 weeks in hypoxia. Rats that received CDP-choline developed less prominent pathological symptoms and died later or remained alive until the end of the experiment. Under conditions of extreme hypoxia CDP-choline exhibited a life-prolonging effect. PMID- 1642666 TI - Effect of vinpocetine on red blood cell deformability in stroke patients. AB - Reduction in red blood cell deformability is a contributory factor in stroke disease, and it has been postulated that red blood cell rigidification may be improved by drug treatment. In this paper the effect of vinpocetine (CAS 42971-09 5) on the deformability of red blood cells from patients with chronic ischemic cerebrovascular disease has been examined. During the administration of vinpocetine for 3 months a significant improvement in red blood cell deformability was observed without adverse effect. PMID- 1642667 TI - Effects of the new angiotensin-I-converting enzyme inhibitor imidapril on the responses of isolated vascular preparations to various agonists. AB - Effects of imidapril hydrochloride ((-)-(4S)-3-[(2S)-2-[[(1S)-1- ethoxycarbonyl-3 phenylpropyl]amino]propionyl]-1-methyl-2- oxoimidazolidine-4-carboxylic acid hydrochloride, imidapril, TA-6366, CAS 89396-94-1), a new prodrug type angiotensin converting enzyme (ACE) inhibitor, and 6366 A (CAS 89371-44-8), an active metabolite of imidapril, on isolated vascular preparations were studied. 6366 A inhibited angiotensin I (AT-I)-induced contraction of the rabbit thoracic aorta at 3 x 10(-10) mol/l or more and augmented bradykinin (BK)-induced relaxation of the dog renal artery precontracted with prostaglandin F2 alpha PGF2 alpha at 10(-9) mol/l or more, whereas imidapril at 10(-7) mol/l did not affect these responses. However, 6366 A, like imidapril, had no effect on angiotensin II (AT-II), norepinephrine, serotonin-, KCl- and PGF2 alpha-induced contractions. The inhibitory effect of 6366 A on AT-I-induced contraction was attenuated by denudation of the endothelium, but it was still maintained even after washing out the aorta that had been previously exposed to the medium containing 6366 A. This suggests that 6366 A persistently inhibits the angiotensin I converting enzyme located preferentially in the endothelium. Therefore, the antihypertensive action of imidapril is mainly attributable to the vasodilation through the inhibitory effects of 6366 A on AT-II synthesis and BK degradation in the vasculature. PMID- 1642668 TI - Metabolic fate of the new angiotensin-converting enzyme inhibitor imidapril in animals. 1st communication: absorption, pharmacokinetics and excretion in rats and dogs. AB - Imidapril hydrochloride ((-)-(4S)-3-[(2S)-2-[[(1S)-1-ethoxycarbonyl-3- phenylpropyl]amino]propionyl]-1-methyl-2-oxoimidazolidine-4-carboxylic acid hydrochloride, imidapril, TA-6366, CAS 89396-94-1) is an ester prodrug of the angiotensin-converting enzyme (ACE) inhibitor, 6366 A (CAS 89371-44-8). Absorption, pharmacokinetics and excretion of imidapril were studied in rats and dogs after oral and intravenous administration of [N-methyl-14C]-imidapril and [N methyl-14C]-6366 A (1 mg/kg). Following oral administration of 14C-labeled imidapril and 6366 A to rats, plasma concentrations of radioactivity were much higher after [N-methyl-14C]-imidapril dosing than after [N-methyl-14C]-6366 A dosing at all time points. Imidapril was relatively rapidly absorbed from the digestive tract and easily metabolized to the pharmacologically active 6366 A after oral dosing in the rats and dogs. Thus, imidapril proved to be an orally usable 6366 A prodrug. More than 62% and 38% of the dose were assumed to be absorbed from the gastrointestinal tract in the rats and dogs, respectively. The in situ absorption study showed that [N-methyl-14C]-imidapril was absorbed from nearly the entire rat small intestine, especially from the jejunum, but hardly absorbed from the stomach. After oral administration, peak levels of radioactivity in the plasma occurred at 1 h in rats and 30 min to 2 h in dogs. The disappearance of unchanged drug from the plasma was much faster in rats than in dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642669 TI - Metabolic fate of the new angiotensin-converting enzyme inhibitor imidapril in animals. 2nd communication: tissue distribution and whole-body autoradiography of imidapril in rats. AB - Tissue distribution, whole-body autoradiography and metabolic profiles in selected tissues of imidapril hydrochloride ((-)-(4S)-3-[(2S)-2-[[(1S)-1 ethoxycarbonyl-3- phenylpropyl]amino]propionyl]-1-methyl-2-oxoimidazolidine-4 carboxylic acid hydrochloride, imidapril, TA-6366, CAS 89396-94-1) were studied in male and female rats after oral and intravenous administration of [N-methyl 14C]-imidapril (1 and 5 mg/kg) or [alanine-3-14C]-imidapril (1 mg/kg). After oral administration of [N-methyl-14C]-imidapril, radioactivity was distributed relatively rapidly to all tissues, except for the central nervous system. Maximum concentrations in most tissues were observed at 30 min to 1 h after dosing. Concentrations greater than those in the plasma were found in the liver, kidney and particularly in the lung except for the gastrointestinal contents. The elimination from the lung was relatively slow (t1/2: ca. 28 h). At 96 h after dosing, there was no evidence of remaining radioactivity in any tissues, except for the lung and kidney. No gender-related differences in the tissue distribution profile of radioactivity were observed in the whole-body autoradiogram. After intravenous administration, the distribution pattern of radioactivity was similar to the results of oral administration, except for the gastrointestinal contents. There was no specific binding of drug-related compounds to melanin-containing tissues such as the hair follicles and the uveal tract of the eye in the pigmented rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642670 TI - Metabolic fate of the new angiotensin-converting enzyme inhibitor imidapril in animals. 3rd communication: tissue accumulation after consecutive oral administration of [N-methyl-14C]-imidapril in rats. AB - Accumulation characteristics of radioactivity in the organs and tissues, metabolism, and excretion of imidapril hydrochloride ((-)-(4S)-3-[(2S)-2-[[(1S)-1 ethoxycarbonyl-3- phenylpropyl]amino]propionyl]-1-methyl-2-oxoimidazolidine-4 carboxylic acid hydrochloride, imidapril, TA-6366, CAS 89396-94-1), an oral angiotensin-converting enzyme inhibitor, were investigated after consecutive oral administration of [N-methyl-14C]-imidapril at a once-daily dose of 1 mg/kg to male rats for 14 days. During the consecutive oral administration, the plasma radioactivity levels at 1 h after each dose reached steady-state following the 3rd to 4th administered dose; this was about 1.4 times higher than the corresponding plasma levels of the first dose. At 24 h after each administration, the plasma levels attained a steady-state at 3-4 days after the beginning of the consecutive dosing. Examination of the time course of plasma radioactivity after the single and multiple (7 and 14 times) oral administration revealed that the Cmax and AUCO-24 h values slightly, but significantly, increased according to repeated dosing and the beta-phase of the t1/2 of disappearance became longer after consecutive dosing. However, these values were not markedly different among consecutive dosing groups. The extent and rate of excretion of radioactivity in the urine and feces were nearly constant during the periods of consecutive oral administration, and were also similar to those after the single oral administration. Total recovery of radioactivity from urine and feces within 96 h after the final dosing was more than 98% of the total dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642671 TI - Metabolic fate of the new angiotensin-converting enzyme inhibitor imidapril in animals. 4th communication: placental transfer and secretion into milk in rats. AB - Imidapril hydrochloride ((-)-(4S)-3-[(2S)-2-[[(1S)-1-ethoxycarbonyl-3- phenylproply]amino]propionyl]-1-methyl-2-oxoimidazolidine-4-car box ylic acid hydrochloride, imidapril, TA-6366, CAS 89396-94-1) labeled with 14C was administered orally or intravenously to pregnant rats on the 13th or 19th day of pregnancy, and lactating rats on the 7th or 13th day after delivery at a dose of 1 or 5 mg/kg. The placental transfer and the secretion into milk were studied using whole-body autoradiographic methods and/or quantitative determination of total radioactivity after autopsy. Irrespective of the stages of pregnancy, the placental transfer of imidapril was low in the rats after oral administration. The transfer of total radioactivity per fetus on the 13th and 19th day of pregnancy was below 0.001 and 0.07%, respectively, of the dose to their dams during the observation periods. This indicates that the substance-associated radioactivity penetrates the placental barrier to a low extent. After oral administration of [N-methyl-14C]-imidapril to lactating rats on the 7th day after delivery, the concentration of radioactivity in the milk attained a peak at 4 h after administration (0.05 microgram equivalents of imidapril/g), which was about 1/3 of Cmax in the blood. The transfer of imidapril and/or its radioactive metabolites to each suckling via milk after oral dosing was only below 0.03% of the dose to the dams on the 13th day after delivery during the observation periods. The present autoradiographic findings confirmed the above results of tissue distribution studies. PMID- 1642672 TI - Metabolic fate of the new angiotensin-converting enzyme inhibitor imidapril in animals. 5th communication: isolation and identification of metabolites of imidapril in rats, dogs, and monkeys. AB - The metabolism of imidapril hydrochloride ((-)-(4S)-3-[(2S)-2-[[(1S)-1 ethoxycarbonyl-3-phenylpropyl]amino] propionyl]-1-methyl-2-oxoimidazolidine-4 carboxylic acid hydrochloride, imidapril, TA-6366, CAS 89396-94-1) was studied in rats and dogs after oral or intravenous administration of [N-methyl-14C] imidapril or [alanine-3-14C]-imidapril, and in monkeys after oral administration of [alanine-3-14C]-imidapril. Radio-chromatographic analysis of the metabolites of imidapril from the plasma, urine, and bile of rats, dogs, or monkeys resulted in the detection of at least four metabolites. These four metabolites were isolated and characterized by high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry(GC-MS). Of these metabolites, M1 (6366 A, CAS 89371-44-8) was pharmacologically active; however, M2, M3, and M4 were inactive. There was no evidence of any glucuronides or sulfates of drug-related compounds, or of the piperazine-dione lactam type metabolites of imidapril or 6366 A in the urine of the animals used. Imidapril was metabolized by hydrolysis at the carboxylic ethyl ester side-chain to give M1, and by cleavage of the amide bond to form M2 and M3. M4 was formed by hydrolysis of M3 and/or cleavage of the amide bond of M1. Qualitatively, the same metabolites were found in all animal species tested; however, quantitatively, there were differences in the amounts of metabolites formed depending on the species. PMID- 1642673 TI - Metabolic fate of the new angiotensin-converting enzyme inhibitor imidapril in animals. 6th communication: interspecies comparison of pharmacokinetics and excretion of imidapril metabolites in rats, dogs, and monkeys. AB - The pharmacokinetics and excretion of the main metabolites of imidapril hydrochloride ((-)-(4S)-3-[(2S)-2-[[(1S)-1-ethoxycarbonyl-3- phenylpropyl]amino]propionyl]-1-methyl-2-oxoimidazolidine-4-carboxylic acid hydrochloride, imidapril, TA-6366, CAS 89396-94-1) were investigated in rats, dogs, and monkeys after oral or intravenous administration of [N-methyl-14C] imidapril and [alanine-3-14C]-imidapril. After oral administration of 14C-labeled imidapril to rats and dogs, the plasma concentrations of the pharmacologically active metabolite, 6366 A (M1, CAS 89371-44-8), reached a peak at 1-2 h in rats and at 2-6 h in dogs. The disappearance half-lives of M1 from plasma were much longer in dogs (6.3-9.3 h) than in rats (0.9-2.3 h). At the point of peak plasma radioactivity, the major radioactive metabolites in the plasma were M2, followed by M3, M4 greater than M1 in rats; in dogs, M2 and M3 followed by M1 greater than M4. After intravenous administration of [N-methyl-14C]-imidapril to rats and dogs, plasma levels of M1 reached a peak at the first measuring time of 5 min in rats and at about 2 h in dogs. The half-lives of plasma M1 levels were similar to those after oral dosing. At 1 h after dosing, the major metabolites in plasma were M1 followed by M2 in both rats and dogs. Irrespective of the route of administration, unchanged imidapril disappeared more rapidly from the plasma in rats than in dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642674 TI - Metabolic fate of the new angiotensin-converting enzyme inhibitor imidapril in animals. 7th communication: in vitro metabolism. AB - In order to clarify the sites of metabolism and the metabolizing enzymes of imidapril hydrochloride ((-)-(4S)-3-[(2S)-2-[[(1S)-1- ethoxycarbonyl-3 phenylpropyl]amino]propionyl]-1-methyl-2- oxoimidazolidine-4-carboxylic acid hydrochloride, imidapril, TA-6366, CAS 89396-94-1), metabolism studies were carried out using rat, dog, monkey, and human plasma and rat tissue homogenates. After incubating with the various plasma samples, imidapril was mainly metabolized to the pharmacologically active metabolite, 6366 A (M1, CAS 89371-44 8), in rat plasma; on the other hand, the ester bond of imidapril was not hydrolyzed in dog, monkey, and human plasma. Imidapril was metabolized to M1, M2, M3, and M4 in all rat tissue homogenates tested. Aside from the above metabolites, no other metabolites were detected. The metabolic activity of imidapril to M1 was the highest in the liver, followed by the kidney and lung; however, it was low in other tissue homogenates. From the results of experiments using certain esterase inhibitors, it has been concluded that the metabolic conversion of imidapril to M1 is mainly due to a carboxylesterase (B-esterase). In contrast, the metabolic activity of imidapril to M2 and M3 (or M4) was highest in the kidney and small intestine while low in other tissues. From the experiments using certain enzyme inhibitors, it has been found that an acetylesterase (C-esterase) is largely involved in the metabolism of imidapril into M2 and M3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642675 TI - Antihypertensive effect of the new dihydropyridine calcium antagonist (+-)-3 (benzylmethylamino)-2,2-dimethylpropyl methyl 4-(2-fluoro-5-nitrophenyl)-1,4 dihydro-2,6-dimethyl-3,5-pyridinedica rbo xylate hydrochloride in dogs. AB - The antihypertensive effect of TC-81 ((+-)-3-(benzylmethylamino)-2,2 dimethylpropyl methyl 4-(2-fluoro-5-nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5 pyridine dicarboxylate hydrochloride, CAS 96515-74-1), a new calcium antagonist, was investigated in normotensive dogs (NTD) and renal hypertensive dogs (RHD). By oral administration, the antihypertensive activity of TC-81 (ED20% was 0.09 mg/kg p.o.) was about 18 times more potent in conscious RHD in comparison with nicardipine (ED20% was 1.65 mg/kg p.o.). Duration of the antihypertensive effect of TC-81 was about 2 times longer than that of nicardipine, and the response was elicited more slowly than that of nicardipine at equipotent dose. Similar results were observed more clearly by intravenous injection, but the potency of TC-81 was only 3 times higher than that of nicardipine in anesthetized dogs. Tolerance of the antihypertensive effect of TC-81 in daily dosing for 2 weeks and the rebound phenomena after discontinuance of the treatment were not observed in RHD. TC-81 at a concentration of 10(10)-3 x 10(-9) mol/l inhibited the KCl- or norepinephrine-induced contraction of isolated dog femoral artery. From these observations, TC-81 can be characterized as having a strong, long-lasting, and slow-onset antihypertensive activity, especially by oral administration. Therefore, this new calcium antagonist may be useful for long-term antihypertensive therapy. PMID- 1642676 TI - Absorption, plasma concentration, and excretion after single administration of 14C-(+-)-3-(benzylmethylamino)-2,2-dimethylpropyl methyl 4-(2-fluoro-5- nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate hydrochloride in rats and dogs. AB - The absorption, plasma concentrations, and excretion of a newly synthesized calcium antagonist, TC-81 ((+-)-3-(benzylmethylamino)-2,2-dimethylpropyl methyl 4 (2-fluoro-5-nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5- pyridinedicarboxylate hydrochloride, CAS 96515-74-1) were studied following a single oral or intravenous administration of 14C-labelled compound. After oral administration, 14C-TC-81 was rapidly and well absorbed from the gastrointestinal tract. The peak plasma concentrations of radioactivity were observed at 0.5-1 h (rats) and 1-2 h (dogs) h after dosing. The elimination of the radioactivity in plasma was biphasic with a half-life of 3.8-5.2 h (a phase) and 42.9-56.2 h (beta phase) in the rats or 3.2 h (a phase) and 61.5 h (beta phase) in dogs. Maximum plasma concentrations of unchanged drug after oral administration of TC-81 to male rats at the doses of 0.5, 1.0, and 3.0 mg/kg were 1.7, 7.3 and 15.6 ng/ml, respectively. They were attained at 0.5 h after dosing in every dose examined. Plasma levels of unchanged drug declined with a half-life of 0.39-1.15 h. When TC 81 was orally administered to male dogs at the doses of 0.1, 0.2 and 0.5 mg/kg, plasma concentrations of unchanged drug reached the maximum level at 0.5 h after dosing and the values were 0.8, 3.3 and 9.6 ng/ml, respectively. They were eliminated with a half-life of 2.4-2.8 h. The absolute bioavailability of unchanged drug was estimated to be 2.6-7.0% (rats) and 5.3-15.5% (dogs) of the dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642677 TI - Distribution to and elimination from tissues following a single or repeated administration of 14C-(+-)-3-(benzyl-methylamino)-2,2-dimethylpropyl methyl 4-(2 fluoro-5-nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedica rbo xylate hydrochloride in rats. AB - A newly synthesized calcium antagonist, TC-81((+-)-3-benzylmethylamino)-2,2 dimethylpropyl methyl-4-(2-fluoro-5-nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5- pyridinedicarboxylate hydrochloride, CAS 96515-74-1) was administered to adult male rats, pregnant and lactating rats with a single oral dose or with repeated doses of 0.3 mg/kg for 2 weeks. The distribution to tissues, placental transfer and secretion of the radioactive drug into milk was studied using whole body autoradiography methods and quantitative determination of total radioactivity after autopsy. 14C-TC-81 was distributed rapidly but disproportionately to the tissues after single administration. The highest concentration of radioactivity was observed in the liver. The radioactivity in the various tissues declined slowly comparing to the plasma but at 96 h after dosing the radioactivity was detected only in the liver. The radioactivity penetrated the blood-placental barrier to a low extent after oral administration of 14C-TC-81 to pregnant rats. When 14C-TC-81 was administered to lactating rats, the radioactivity was secreted into the milk with the maximum concentration of radioactivity, 86% of the corresponding plasma concentration. Following 14-day oral treatments of male rats the equivalent concentration in the plasma was increased 1.5 fold as compared to the single treatment. In all tissues, the AUC0-24 h after 1, 7, and 14 days treatment were gradually increased, but these increases were almost the same as or even less than the rise observed in the plasma. After the last dosing, the radioactivity declined slowly with time in most of the tissues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642678 TI - Analysis of the daily variation in blood pressure and pharmacokinetics after single or repeated administration of clentiazem to patients with essential hypertension. AB - Clentiazem (TA-3090, CAS 96125-53-0), a new benzothiazepine Ca++ antagonist, was orally administered to inpatients with essential hypertension at a dose of 30 mg at 8:00 a.m. once (n = 5) or daily for 2 weeks (n = 22). After administration of the medication, the daily variations in blood pressure and pulse rate were monitored using a portable blood pressure recorder, and plasma concentrations of clentiazem were determined by HPLC. 1. In the single administration study, an antihypertensive effect was observed between 4 and 12 h with a peak approximately 8 h after administration. After the single dose, the diurnal pulse rate was higher than the pretreatment level, but it was not correlated with the antihypertensive effect. 2. In the repeated administration study, both the systolic and diastolic blood pressures showed significant decreases after administration throughout the day (p less than 0.01). The nocturnal antihypertensive effect was weaker than the diurnal effect, and the minimum decrease/maximum decrease ratio in a day was 0.52 for both systolic and diastolic pressures. The pulse rate decreased slightly during certain time intervals after administration (p less than 0.01 or p less than 0.05), but those were slight changes. 3. As to the pharmacokinetic profile clentiazem showed a long-lasting plasma level, the tmax was 6.8 +/- 1.1 h for the single treatment and 6.9 +/- 1.6 h for the repeated treatment; the Cmax was 16.9 +/- 6.1 ng/ml and 19.3 +/- 8.8 ng/ml, respectively; and the t1/2 was 6.6 +/- 1.5 h and 12.5 +/- 5.4 h, respectively. The plasma level profiles for single and repeated administrations were similar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642679 TI - Hemodynamic effects of cilostazol on peripheral artery in patients with diabetic neuropathy. AB - On the basis of vascular involvement, an open clinical trial was performed to determine whether or not the antithrombotic drug cilostazol (6-[4-(1-cyclohexyl 1H-tetrazol-5-yl) butoxy]-3,4-dihydro-2(1H)-quinolinone, OPC-13013, Pletaal, CAS 73963-72-1) applied as a single 100 mg tablet increases peripheral blood flow and prevents diabetic neuropathy in 30 patients with non-insulin dependent diabetes mellitus. The hemodynamic effects of this drug on the a. dorsalis pedis were examined using a new real-time two-dimensional Doppler echography. 1 h after oral administration of cilostazol, the cross-sectional area of the a. dorsalis pedis significantly increased from 2.2 +/- 0.2 to 2.9 +/- 0.3 mm2 (p less than 0.05). Also, the a. dorsalis pedis blood flow index significantly increased from 16 +/- 1 to 31 +/- 4 (p less than 0.05). Cilostazol did not affect plasma glucose level (from 213 +/- 14 to 198 +/- 15 mg/dl), but slightly plasma ratio of 6-keto PGF1a to TXB2 (from 0.71 +/- 0.09 to 0.83 +/- 0.12). These effects of cilostazol might ameliorate diabetic neuropathy by improving blood flow and preventing nerve tissue ischemia. PMID- 1642680 TI - [Anti-inflammatory activity of sabal fruit extracts prepared with supercritical carbon dioxide. In vitro antagonists of cyclooxygenase and 5-lipoxygenase metabolism]. AB - The extract SG 291 (Talso, Talso uno) from the fruits of Sabal serrulata (syn.: Serenoa repens) prepared by supercritical fluid extraction with carbon dioxide is used for the treatment of benign prostatic hyperplasia (BPH) and non bacterial prostatitis. In the present work, the Sabal extract SG 291 was analyzed by gas chromatography and investigated for its inhibitory influence on the biosynthesis of inflammatory arachidonic acid metabolites. The extract SG 291 was found in vitro to be a dual inhibitor of the cyclooxygenase (IC50-value: 28.1 micrograms/ml) and 5-lipoxygenase pathway (IC50-value: 18.0 micrograms/ml). By alkaline hydrolysis, ether extraction and preparative thin layer chromatography the extract SG 291 was separated in three fractions containing acid lipophilic compounds (A), fatty alcohols (B) and sterols (C) as main components. Fraction A inhibited the biosynthesis of cyclooxygenase (CO) and 5-lipoxygenase (5-LO) metabolites in the same intensity as the native extract SG 291, while the fractions B, C and beta-sitosterol showed no inhibitory effect on both enzymes of the arachidonic acid pathways. Therefore, the CO and 5-LO inhibiting principle of Sabal serrulata extract SG 291 must be localized in the acidic lipophilic fraction (SLF). The CO and 5-LO inhibitory effects may give an explanation for the in vivo observed antiphlogistic and antiedematous activity of the lipophilic Sabal serrulata extract SG 291. PMID- 1642681 TI - [Pharmacokinetic aspects of a combination of metoclopramide and paracetamol. Results of a human kinetic study and consequences for migraine patients]. AB - An open trial was carried out in eight healthy male and female volunteers to examine the bioavailability as well as the main kinetic parameters of Migranerton (metoclopramide and paracetamol; CAS 364-64-5 and CAS 103-90-2, resp). in comparison with reliable literature data. The results reported here clearly show that the absorption of both active ingredients from the fixed combination is complete and that therapeutically relevant plasma concentrations are achieved within 30 min. Bioavailability as well as tmax, t1/2, and time-lag are comparable with data resulting from reliable and internationally acknowledged kinetic studies. The fixed combination was shown to be kinetically compatible with regard to all parameters determined for metoclopramide and paracetamol. PMID- 1642682 TI - Activity and pharmacokinetics of a new oral dosage form of soluble ibuprofen. AB - The pharmacokinetics and the relative bioavailability of a soluble granular form (sachets) of a pharmaceutical formulation containing ibuprofen (CAS 15687-27-1) and 1-arginine were investigated in healthy volunteers. Two granular dosage forms were evaluated, 200 and 400 mg, in comparison with the commercial equivalents (tablets). After the oral administration of both granular dosage forms, a quicker absorption and a significantly higher plasma bioavailability of ibuprofen in the first hour following the treatment than after tablets administration were observed. The mean values of peak plasma concentration (microgram/ml) were 26.1 and 56.4 after treatment with 200 and 400 mg sachets respectively vs. 16.3 and 43.0 after treatment with 200 and 400 mg tablets. The mean values of peak time were 16.9 and 24.4 min after treatment with 200 and 400 mg sachets respectively vs. 90.0 and 63.7 min after treatment with 200 and 400 mg tablets. The shortening in the absorption time and the increase in the plasma concentrations did not involve a quicker drug elimination nor cause any changes in the bioavailability (mean values of the relative bioavailability indexes of 0.98 for 200 mg dosage form and 1.02 for the 400 mg one). The analgesic activity of soluble ibuprofen 400 mg was compared with that of ibuprofen 400 mg tablets in patients with osteo articular pain, according to a single dose, double-blind cross-over balanced design. The results showed that the soluble granular form is able to determine an analgesic effect significantly quicker and higher than that of tablets. PMID- 1642683 TI - Osteopenia in rats with drug-induced mucopolysaccharidosis. AB - The immunostimulatory drug tilorone (CAS 27591-97-5) induces generalized lysosomal storage of sulfated glycosaminoglycans, i.e., mucopolysaccharidosis (MPS) in rats. Since inherited MPS of man is often associated with skeletal lesions the present study was performed to investigate whether the tilorone induced MPS is also accompanied by bone alterations. The answer is yes. Rats (initial age 4 weeks) were orally treated with tilorone (60-80 mg/kg; 6-25 weeks). The proximal tibial metaphysis was examined by radiography and by light and electron microscopy. The tibiae of drug-treated rats remained smaller than those of pair-fed control rats. The primary bone trabecules in drug-treated rats became increasingly shorter, and the cortical bone became thinner. The general organization of the cartilaginous growth plate and the zones of vascular invasion and primary trabecule formation appeared similar as in control rats. Increased numbers of active osteoclasts were found at the free ends of the primary trabecules. Ultrastructurally, MPS-like alterations were observed in all types of bone cells. The osteopenia was partly reversible during recovery periods of more than 6 months after discontinuance of drug treatment. At present, the causal relationship between drug-induced MPS and osteopenia, as well as the mechanisms responsible for osteopenia are unknown. It is suggested that the principal factors are stimulation of osteoclasts and retardation, though not profound distortion, of the events involved in enchondral ossification. PMID- 1642684 TI - Effect of cefodizime on parameters of cell-mediated immunity in vitro. AB - A positive effect of cefodizime (CAS 69739-16-8), a new aminothiazolyl cephalosporin, on a number of immunological variables, and in particular phagocytosis, was demonstrated in several test systems. The aim of the present investigation was to establish whether clinically relevant concentrations of cefodizime affect cell-mediated immune variables. Peripheral lymphocytes from healthy subjects were isolated and incubated with cefodizime in increasing concentrations from 0 to 200 mg/l. The effects of cefodizime on membrane-bound antigenic determinants of the lymphocytes were determined in the rosette inhibition test, and its effects on the proliferative capacity of lymphocytes after stimulation with phytohaemagglutinin, concanavalin A and pokeweed mitogen were determined in the lymphocyte transformation test. Cefodizime inhibited rosette formation in a concentration dependent manner. A direct inhibitory effect on proliferation was not, however, demonstrated in the lymphocyte transformation test. Indeed, stimulation of mitogen-induced lymphocyte transformation, particularly of concanavalin A-sensitive cells was observed at concentrations higher than 100 mg/l. The findings in healthy volunteers were reproduced in samples from three female patients with impaired host-defence. These results may suggest a positive effect of cefodizime on the proliferative capacity of the cellular immune system. However, no conclusions can be drawn on the clinical relevance of these findings until the results of in vivo investigations are available. PMID- 1642685 TI - [Structural characterization of an unknown metabolite of ciprofloxacin]. AB - The chemical structure of an unknown metabolite of ciprofloxacin (CAS 85721-33-1) is characterized by means of reversed phase ion pair liquid chromatography, absorption and fluorescence spectroscopy, partition coefficients as well as chemical and enzymatic hydrolytic degradation. A chemical structure of the unknown metabolite is proposed: N-formyl-desethylen-ciprofloxacin. It can be formed as an intermediate in the oxidative degradation of ciprofloxacin via oxociprofloxacin to desethylen-ciprofloxacin, or it may be formed by conjugation of desethylen-ciprofloxacin with formic acid. The amounts found in plasma and urine of patients were in the range of desethylen-ciprofloxacin, i.e. about 1% of the parent compound. PMID- 1642686 TI - Distribution of recombinant human erythropoietin following multiple intravenous administration and effects of age on the distribution in rats. AB - Multiple administration of 125I-recombinant human erythropoietin (125I-rh-EPO) did not cause an accumulation of intact EPO in tissue. The gel filtration profile of tissue from rats given multiple doses of 125I-rh-EPO was very similar to that for rats given single doses of 125I-rh-EPO, suggesting that intact rh-EPO (CAS 11096-26-7) does not accumulate. Pretreatment of rats with non-labeled rh-EPO did not cause a change in the ratio of metabolites to intact rh-EPO, as judged by the gel filtration data. This indicates that multiple administrations do not cause a change in metabolic pathways in the tissues. The tissue to plasma concentration ratio (t/p ratio) of rh-EPO in the target organ, i.e., the bone marrow and spleen, decreased with increase of age; the spleen showed a marked decrease in t/p ratio as compared to the bone marrow. On the other hand, t/p ratios in the kidney and liver did not change for periods of 4 to 31 weeks. PMID- 1642687 TI - Regression of coronary atherosclerosis by combined LDL-apheresis and lipid lowering drug therapy in patients with familial hypercholesterolemia: a multicenter study. The LARS Investigators. AB - The purpose of the LDL-Apheresis Regression Study (LARS) group, which included 13 institutions in Japan, was to investigate the effects on coronary atherosclerosis of LDL-apheresis combined with cholesterol-lowering drugs. Changes in coronary artery stenosis were assessed angiographically in 37 patients with familial hypercholesterolemia (7 homozygotes and 25 heterozygotes) and hypercholesterolemia which had not been defined as familial hypercholesterolemia (5 patients) by visual judgement and computer analysis. Definite regression was observed in 14 cases, including 4 homozygotes and 10 heterozygotes and others. Regression occurred as often in patients with severe coronary artery disease (2 or more vessel disease) as in those having less severe disease. Our results encourage initiation of aggressive cholesterol-lowering therapy to produce regression of coronary atherosclerosis in FH patients at high risk for cardiovascular events. PMID- 1642688 TI - Seasonal variation in serum cholesterol levels--evidence from the UK and Japan. AB - Using data from 140,000 men and 32,000 women in the UK and 30,000 men and 12,000 women in Japan, we performed spectral analyses to test for seasonal variation in serum cholesterol levels. In both countries and both sexes we found a strong seasonal effect, cholesterol levels being some 3-5% higher in winter than in summer. This was independent of seasonal changes in body mass. Mean monthly cholesterol levels were negatively correlated with mean monthly air temperatures (r = -0.60 to -0.71). The observed seasonal differences were larger than the inter-assay coefficient of variation for the cholesterol determination method employed and have important consequences for long-term epidemiological or intervention studies. PMID- 1642689 TI - Non-cholesterol sterols, absorption and synthesis of cholesterol and apolipoprotein A-I kinetics in a Finnish lecithin-cholesterol acyltransferase deficient family. AB - We describe the first Finnish LCAT-deficient family with two affected, one questionably affected and one healthy family member. The affected family members presented stomatocytes in the peripheral blood, exhibited low serum levels of total, LDL and HDL cholesterol, triglycerides, phospholipids and apolipoprotein A I and especially A-II. Apolipoprotein A-I catabolism was accelerated to moderately high and very high levels in the two affected subjects. Cholesterol esterification percentage was low in all lipoprotein fractions. The intestinal cholesterol absorption efficiency and cholesterol and bile acid synthesis were within normal limits. The esterification percentage of demethylated cholesterol precursor sterols, cholestanol and plant sterols resembled mostly that of cholesterol, while those of VLDL and LDL methostenols, precursor sterols esterified by acyl-CoA:cholesterol acyltransferase (ACAT), suggested normal ACAT activity. In HDL all sterols were poorly esterified. The observations on stomatocytes, normal absorption and synthesis of cholesterol and bile acids, abnormal kinetics of apolipoprotein A-I, evidence of normal ACAT activity and abnormal esterification of non-cholesterol sterols are findings presented for the first time in LCAT deficiency. PMID- 1642690 TI - Effect of gemfibrozil on composition of lipoproteins and distribution of LDL subspecies. AB - We studied the effect of gemfibrozil on the compositions of VLDL, LDL and distribution of LDL subspecies in type II hyperlipidemic patients. Gemfibrozil significantly lowered serum triglyceride levels in this group of patients who had normal to moderately elevated triglyceride prior to therapy. Gemfibrozil also changed the composition of VLDL by lowering its free cholesterol, cholesterol ester and raising the protein content. In contrast, no measurable changes in LDL chemical composition were found following gemfibrozil therapy. Changes in LDL, however, can be detected using ultracentrifugal and electrophoretic methods. Peak densities of LDL were lowered and LDL subspecies shifted to larger, slower-moving bands on gradient gel electrophoresis in patients receiving gemfibrozil treatment. These results suggest that gemfibrozil treatment resulted in qualitative changes in both VLDL and LDL even in patients with moderately elevated baseline serum triglyceride levels. PMID- 1642691 TI - Poland-US collaborative study on cardiovascular epidemiology: classification agreement between US National Cholesterol Education Program and European Atherosclerosis Society hyperlipidemia guidelines in selected Polish and US populations. AB - Data from two epidemiological studies are used to measure the degree to which two well-known guidelines agree in measuring hyperlipidemia in population samples in the US and Poland. The epidemiological studies are the US Lipid Research Clinics Program Prevalence Study and the Pol-MONICA project in Poland and the guidelines are those adopted by the US National Cholesterol Program (USNCEP) and by the European Atherosclerosis Society (EAS). EAS guidelines were analyzed in two ways: Method 1 used triglycerides and total cholesterol only in classifying persons as hyperlipidemics or non-hyperlipidemics; Method 2 used triglycerides, total cholesterol and nine additional risk factors in the classification process. USNCEP guidelines used total cholesterol, low density lipoprotein cholesterol and the same additional nine risk factors used in EAS Method 2 in classifying hyperlipidemics. Classification differences between the two sets of guidelines were high when EAS Method 1 guidelines were compared with USNCEP guidelines. However, EAS Method 2 which included risk factors, compared favorably with USNCEP guidelines in all three populations under study. PMID- 1642692 TI - Priming effect of adrenic acid (22:4(n-6)) on tissue factor activity expressed by thrombin-stimulated endothelial cells. AB - Tissue factor (TF) which initiates clotting process can be expressed by stimulated endothelial cells (EC). TF is an apolipoprotein requiring an association with phospholipids (PL) in order to become active. Also PL constitute an important storage pool of polyunsaturated fatty acids (PUFAs) in EC which can be modulated by diet or cell medium supplementation. In order to test the effect of such manipulation upon TF activity, we have pre-enriched human EC cultures with different fatty acids of nutritional interest. TF was evaluated after 4 h of thrombin stimulation by using a chromogenic method. Without additional stimulating agents, these acids have no effect on the basal level of TF. Eicosapentaenoic and docosapentaenoic acids appeared to be ineffective at the stimulated TF level. Only adrenic acid (22:4(n-6)) has been found to significantly enhance TF activity of thrombin-stimulated endothelial cells. Other TF inducers were also tested after 22:4(n-6) enrichment. An increase tendency of TF expression was found only with tumor necrosis factor, whereas interleukin-1 beta, lipopolysaccharide and especially phorbol myristate acetate stimulations were not significantly modified. The priming effect of adrenic acid on thrombin stimulated TF expression might involve alterations of signal transduction pathways rather than modifications of apolipoprotein III environment. Adrenic acid, which is a prostacyclin inhibitor, appears to be potential prothrombotic agent. PMID- 1642693 TI - Enhanced incorporation of [14C]glucosamine into glycosaminoglycans of aortic neointima of balloon-injured and cholesterol-fed rabbits in vitro. AB - Glycosaminoglycans (GAG), which form the elementary constituent of extracellular matrix proteoglycans (PG), are implicated in the pathogenesis of atherosclerosis, mainly due to their lipoprotein binding capability and their abundance in a developing lesion during atherogenesis. However, the reasons for the increment of GAG content are poorly understood. In the present study, the influence of two well known atherogenic factors on arterial GAG synthesis were examined by estimating the incorporation of [14C]glucosamine into aortic GAG in an in vitro incubation system. Radioactivity associated with GAG was taken to represent their synthesis. GAG synthesis by neointimal tissue of rabbit aortas, 12 weeks following balloon catheter deendothelialization was measured and compared in rabbits fed a normal or 0.25% cholesterol supplemented diet for the preceding 6 weeks. In normolipaemic rabbits synthesis was found to be 12,438 +/- 173, 17,884 +/- 1390 and 15,960 +/- 1355 dpm/mg dry defatted tissue from uninjured (control), deendothelialized (DEA) and reendothelialized (REA) areas of rabbit aortas, respectively. This incorporation of radioactivity was significantly greater in hypercholesterolaemic rabbits corresponding to 13,426 +/- 239, 32,670 +/- 3077 and 27,496 +/- 3287 in the control, DEA and REA, respectively. The results demonstrated a synergistic effect of cholesterol feeding and arterial endothelial denudation in stimulating GAG synthesis. Although GAG synthesis was found to be stimulated by either cholesterol feeding or arterial injury, the stimulation by cholesterol feeding alone was only marginal. Further, results show a much higher retention of newly synthesized GAG by the tissue from REA. This study provided a possible explanation for increased GAG content in a developing proliferative lesion. PMID- 1642694 TI - Differential effects of nicotinic acid in subjects with different LDL subclass patterns. AB - Twenty-six subjects (20 male, 6 female) at high risk for CAD events were treated with moderate doses of nicotinic acid to investigate whether there was a differential lipoprotein response in patients with different LDL subclass patterns. Subjects were selected to have either pattern A (predominance of large LDL, peak particle diameter greater than 262 A, n = 9) or pattern B (predominance of small LDL, peak particle diameter less than 255 A, n = 17) as assessed by 2 16% gradient gel electrophoresis of plasma. Nicotinic acid dose was similar in pattern A (2111 +/- 651 mg/day) and pattern B subjects (1875 +/- 698 mg/day). Total cholesterol and LDL cholesterol decreased by similar amounts in pattern A ( 41 +/- 26 mg/dl and -37 +/- 18 mg/dl) and pattern B (-51 +/- 44 mg/dl and -44 +/- 45 mg/dl) subjects. Triglycerides tended to be reduced more in pattern B subjects (-100 +/- 175 mg/dl) compared to pattern A subjects (-23 +/- 34 mg/dl) although this difference was not statistically significant (P = 0.08 for triglycerides log transformed). HDL cholesterol increased significantly more in the pattern B group (11.9 +/- 14.2 mg/dl) compared to pattern A subjects (0.7 +/- 8.5 mg/dl), (P less than 0.04). Similarly, LDL particle diameter increased significantly more in the pattern B subjects (9.8 +/- 6.9 A) compared to the pattern A subjects (3.6 +/- 3.0 A), (P less than 0.02). All pattern B subjects who achieved a plasma triglyceride less than 140 mg/dl converted to pattern A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642695 TI - Inhibition of cultured vascular smooth muscle cell migration by simvastatin (MK 733). AB - The effect of simvastatin (MK-733), a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on the migration of cultured porcine smooth muscle cells (SMCs) was investigated in modified Boyden chambers. Platelet derived growth factor (PDGF) stimulated the SMC migration dose dependently. MK 733 inhibited the migration response induced by PDGF with an IC50 value of 2 microM. Supplementation with mevalonate restored the migration response inhibited by MK-733 but the addition of low-density-lipoprotein (LDL) did not change the response. Another HMG-CoA reductase inhibitor, pravastatin (CS-514), also reduced the migration response. However its potency was far less than that of MK-733. MK 733 also inhibited the SMC migration stimulated by fibrinogen. These results suggest that non-sterol metabolite(s) of mevalonate, possibly prenylated proteins, are involved in a migration signaling pathway and that HMG-CoA reductase inhibitors are effective in the prevention of the formation of intimal hyperplasia in atherosclerosis. PMID- 1642696 TI - Hypercholesterolemia induces differential expression of rabbit apolipoprotein A and C genes. AB - We have compared steady-state mRNA levels of apolipoproteins AI, AII, AIV, CI, CII and CIII in liver and small intestine of rabbits fed on a cholesterol-rich diet for up to 16 weeks. Apolipoprotein (apo) AIV mRNA was detected in both liver and small intestine, while apo AII was not detected in either organ. Apo CI, apo CII and apo CIII were expressed only in liver and apo AI mRNA was detected only in small intestine. In small intestine, apo AIV and apo AI mRNA levels increased to a maximum at the 4th and 12th week of treatment, respectively. In liver there was a parallel increase in the mRNA levels of apo AIV, apo CI, apo CII and apo CIII, with maximum levels after 4 weeks of treatment. A 3-fold increase was found in apo CII and apo CIII hepatic transcription rates between hypercholesterolemic and control rabbits after 4 weeks of treatment, no longer detectable after 8 weeks. However, no changes were found in apo AIV and apo CI transcription rates. Changes in apolipoprotein mRNA levels were accompanied by changes in plasma lipoprotein levels. Overall, these changes correlate well with the variations detected in the expression of the different apolipoprotein genes. Our results indicate that dietary cholesterol plays an important role in the regulation of these genes and that this regulation is tissue dependent. PMID- 1642697 TI - 'HIV transmission via blood and saliva splashes to the face'. PMID- 1642698 TI - Junior doctors on the warpath. PMID- 1642699 TI - Psoriatic arthritis precipitated by physical trauma: destructive arthritis or associated with reflex sympathetic dystrophy? PMID- 1642701 TI - The incidence of ethanol-induced hypoglycemia. AB - The purpose of the study was to determine the incidence of ethanol-induced hypoglycemia. All nondiabetic patients who had blood alcohol levels above 0.10% and a random serum chemistry drawn (including glucose) were included. Over a 6 month study period, 378 patients were included in the study. Fifteen patients (4%) presented with hypoglycemia (glucose less than 67 mg%). Of these, four (1%) were profoundly hypoglycemic (glucose less than 50 mg%). Two hundred and fifty three patients (67%) patients were normoglycemic (glucose 67-106 mg%) and 110 patients (29%) were hyperglycemic (glucose greater than 106 mg%). Nonfasting glucose measurements from a control group of 96 nondiabetic, nonintoxicated patients were compared with those of the study group. Two patients (2%) presented with hypoglycemia and none (0%) presented with profound hypoglycemia. Forty-five patients (47%) presented with normoglycemia, and 49 (51%) with hyperglycemia. There were no statistically significant differences found in the hypoglycemia rate between the intoxicated patients and nonintoxicated control population (odds ratio of 0.75; P greater than .05). Four of 378 intoxicated patients (1%) had profound hypoglycemia (less than 50 mg/dL) compared with none (0%) of the 96 nonintoxicated patients. Intoxicated patients had a statistically significant lower rate of hyperglycemia in comparison with the nonintoxicated control group (29% versus 51%; P less than .0001). Age, sex, race, ethanol level, and serum electrolyte measurement had no predictive value for hypoglycemia in intoxicated patients. The anion gap was consistently elevated in hypoglycemic patients in comparison with normoglycemic patients (P less than .05). Hypoglycemia appears to occur as frequently in an ethanol-intoxicated population as in a population without elevated ethanol levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642700 TI - Effect of administration of thyroxine on the risk of postpartum recurrence of hyperthyroid Graves' disease. AB - In our previous study, we reported that the administration of T4 to patients with Graves' disease who were under treatment with methimazole (MMI) decreased the level of antibodies to thyroid-stimulating hormone (TSH) receptors and the rate of recurrence of hyperthyroidism. In this study, the effect of T4 administration on the rate of postpartum recurrence of hyperthyroidism was examined. Seventy eight patients with Graves' disease had been treated with MMI for 1-3 yr before pregnancy, and MMI was discontinued 5-6 months after the onset of pregnancy because the levels of antibodies to TSH receptors decreased during early pregnancy. The patients were then divided into two groups. Group A (n = 40) was given T4 (100 micrograms/day) and group B (n = 38) was not given any drugs from 5 months after the onset of pregnancy until 1 yr after delivery. The levels of the antibodies to TSH receptors and serum concentrations of thyroxine-binding globulin (TBG) and T4 were not different between the two groups before and during pregnancy, although a transient increase in serum T4 and TBG concentrations were observed during the pregnancy in both groups. After delivery, levels of antibodies to TSH receptors increased in both groups. The rate of increase, however, was more rapid in group B than in group A. The levels were significantly higher in group B than A at 3, 6, 9, and 12 months after delivery. Serum T4 and TBG concentrations decreased after delivery in both groups. Serum concentrations of T4 increased after delivery in group B but not in group A. The concentration of T4 was significantly higher in group B than in group A at 9 and 12 months after delivery. Postpartum recurrence of hyperthyroidism was 5.0% in group A and 31.6% in group B, respectively, during the first year after delivery. These results suggest that administration of T4 during pregnancy and after delivery is effective in decreasing the level of antibodies to TSH receptors and to prevent the postpartum recurrence of hyperthyroidism. PMID- 1642702 TI - Early identification of acute myocardial infarction and prognosis in relation to mode of transport to hospital. AB - Of 2,840 consecutive patients who were admitted to the emergency department of a Swedish university hospital due to suspected acute myocardial infarction (AMI), only 25% were reached by the mobile coronary care unit (MCCU), and only 4% simultaneously fulfilled traditional criteria for prehospital thrombolysis (ie, had ST-segment elevation on admission electrocardiogram and a delay time of less than 6 hours). In the subset of patients who fulfilled criteria for a confirmed AMI, 31% were reached by an MCCU and 11% fulfilled criteria for prehospital thrombolysis. Among patients with confirmed AMI, the hospital mortality rate was highest in patients transported by standard ambulance (19%) versus 15% in those transported by an MCCU and 8% in those transported by other means. The authors conclude that AMI patients transported by ambulance are high-risk patients for early death. Prehospital thrombolysis might reduce their rate of mortality. However, according to the authors' experience only a minor fraction of patients are available for prehospital thrombolysis. PMID- 1642703 TI - Compliance with emergency department patient referral. AB - This study evaluated the nature and efficacy of compliance with emergency department (ED) patient referral recommendations. This was a prospective, nonrandomized, descriptive analysis of all ED patients referred mandatorily to an established urban hospital follow-up network. Compliance was measured by analysis of hospital records determined as appointment completion. Patient demographics, urgency of complaint, hospital relationship (new versus established), diagnosis (International Classification of Diseases-9CM), specialty, and method of payment, defined as clinic or private referral, were determined. Comparisons between groups used Fisher's exact test and chi 2 analysis (alpha = 0.05). There were 2,185 patients encountered with 1,443 (66%) discharged for referral, and an overall compliance rate of 27.8% (401 patients). Patients had a mean age of 36.9 years; 50.6% were male, 94.4% were established patients, 51.1% were clinic cases, and 96.7% had nonurgent complaints. Patients encountered had higher rates of compliance if female (33.9%), greater than 40 years of age (43.4%), with urgent complaints (46.8%), and if referred to private physicians (37.0%) (P less than .001). Compliance also correlated with the diagnosis of fracture (63.3%) or laceration (45.6%); and specialty referral to obstetrics-gynecology (28.4%) and general surgery (22.4%) consultants (P less than .01). Most patients demonstrate low compliance (28%) with follow-up recommendations, even with a directed ED referral system. PMID- 1642704 TI - Paramedic intubation training in a pediatric operating room. AB - The authors conducted a prospective study to assess the performance of paramedics with prior adult endotracheal intubation experience in pediatric intubation in the operating room of a teaching hospital. Nineteen paramedic students were observed attempting endotracheal intubation on a total of 57 anesthetized pediatric patients undergoing scheduled surgical procedures. The average age of patients was 5.1 years (range, 6 months to 15.2 years). Average duration of intubation attempts was 22.7 +/- 10.7 seconds, with a success rate on first attempt of 74%. Only minor complications occurred, and were limited to intubation attempts of greater than 45 seconds duration in four cases (6%), and patient oxygen saturation less than 90% in one case (2%). The study suggests that paramedics may be successfully incorporated into a hospital's clinical training program, and can receive closely supervised experience in pediatric endotracheal intubation without compromising patient care. Such training may increase the willingness of paramedics to attempt emergent prehospital endotracheal intubation of children, as well as increase their success with this potentially life-saving procedure. PMID- 1642705 TI - Steroids for the treatment of corrosive esophageal injury: a statistical analysis of past studies. AB - Caustic esophageal injury causes substantial morbidity and mortality. However, the use of corticosteroids to treat this problem has been evaluated in a limited number of studies because adequate sample size is difficult to obtain. We analyzed 361 subjects with corrosive esophageal injury derived from 10 retrospective and three prospective publications. We divided cases into those treated with corticosteroids and antibiotics (T) and those that received neither modality (NT) based on inclusion and exclusion criteria. Forty-one percent of NT cases developed esophageal stricture and 19% of T cases developed this complication (P less than .01). There were no reported strictures among 72 first degree esophageal burns (combined T and NT cases). The T group contained 54 strictures among 228 patients (24%) with either second- or third-degree burns. The NT group of 25 patients with the same burn severity suffered 13 strictures (52%) (P less than .01). Reports of death and gastrointestinal hemorrhage did not increase among steroid-treated patients. We do not recommend corticosteroid therapy for first-degree esophageal injuries. However, this therapy may be useful in preventing strictures among patients with second- or third-degree corrosive esophageal burns. PMID- 1642706 TI - Acute nutmeg intoxication. AB - Nutmeg is a common household spice sometimes abused for its hallucinogenic properties. This abuse is well reported in the medical literature over the last century. Ingestion of less than one tablespoon can produce symptoms similar to those of an anticholinergic toxic episode. Common presenting complaints are hallucinations, palpitations, and feelings of impending doom. We report a case of intentional nutmeg intoxication in a 23-year-old college student. As laboratory tests are usually normal, this diagnosis should be considered in patients presenting with an acute psychotic break accompanied by symptoms resembling an anticholinergic toxic episode. Treatment is primarily supportive once other life threatening conditions have been ruled out. PMID- 1642707 TI - "Pneumo-ptosis" in the emergency department. AB - The authors report the case of a 16-year-old female who presented with a left tension pneumothorax and a left Horner's syndrome. Chest tube thoracostomy performed to relieve the tension pneumothorax also resulted in the immediate resolution of the patient's ptosis and miosis. The probable mechanism for the patient's focal neurologic signs was traction upon the cervical sympathetic chain secondary to the mediastinal shift of the tension pneumothorax. This case demonstrates that unequal pupils in the presence of a pneumothorax could represent Horner's syndrome. PMID- 1642708 TI - Bedside visual colorimetry of peritoneal lavage fluid in abdominal trauma patients. PMID- 1642709 TI - Tetanus. AB - Tetanus is a preventable disease with proper immunization. The marked decline in the incidence over the past several decades has resulted from widespread use of tetanus prophylaxis and improved wound management in the emergency department. Emergency physicians are among the most frequent providers of tetanus vaccination. We can stress the importance of proper immunization and encourage patients to keep accurate immunization records. This can maximize protection of patients from tetanus, and minimize adverse reactions from excessive administration of booster. Tetanus can be fatal even with proper treatment. Vital treatment measures can easily be completed in the emergency department. PMID- 1642710 TI - Cases in electrocardiography. PMID- 1642711 TI - 1991 annual report of the American Association of Poison Control Centers National Data Collection System. PMID- 1642712 TI - Intubation of patients with cervical spine injuries. PMID- 1642713 TI - Threefold increase in theophylline serum concentration after addition of mexiletine. PMID- 1642714 TI - Ultraviolet light-induced keratitis secondary to germicidal lamp exposure resulting in corneal epithelial sloughing. PMID- 1642715 TI - Breathing pattern and subjective responses to small inspiratory resistance during submaximal exercise. AB - Breathing patterns and subjective responses to small resistances were investigated in seven subjects during moderate exercise. Inspiratory resistances of 0.15 (R1), 0.25 (R2) and 0.30 (R3) kPa.l-1.s were tested against control of 0.06 kPa.l-1.s with no added resistance. Subjective responses to small inspiratory resistances were evaluated through whole experiments including periods before and after exercise, herein called SNS. Average SNS significantly increased above the R2 condition. Above the R2 condition, significant changes in the breathing components of volume, flow and timing were also observed during exercise. SNS grew as a power function of peak inspiratory pressure (P(imax)) measured during exercise within such small range of stimulation less than the R3 condition and individual differences in the relationship between SNS and P(imax) were observed. All subjects felt at least some discomfort below the resistance of R3 and two subjects felt it below around R1 condition. It was suggested that breathing pattern was selected to limit peak pressure at the R3 condition by further increasing inspiratory work for a breath and this tendency was reinforced in load-sensitive subjects with longer inspiratory time and lower peak flow rate. We concluded that breathing patterns depend mainly on peak work, especially in load-sensitive individuals, which is likely to be one of the primary determinants of a worker's tolerance to respirators. PMID- 1642716 TI - Pulmonary gas exchange dynamics and the tolerance to muscular exercise: effects of fitness and training. AB - Oxygen uptake (VO2) kinetics are generally agreed to be first-order for moderate work rates with a time constant (tau VO2) that is thought to reflect the kinetics of intramuscular creatine phosphate depletion. However, when there is a concomitant lactic acidosis, tau VO2 is appreciably longer, reflecting an additional, delayed and slowed component that leads to VO2S greater than the aerobic equivalent of that work rate and which therefore invalidates current techniques for O2 deficit estimation. This "excess" VO2 is no more than approximately 250-300 ml/min at work rates for which [lactate] and [H+]a can be stabilized. At higher work rates which demand sustained and progressive increases in [lactate] and [H+]a, however, VO2 also continues to increase progressively, yielding excess VO2S greater than 11/min at exhaustion. The trajectory of excess VO2 therefore is to the maximum VO2: the resulting exercise limitation becomes progressively more pronounced the higher the work rate, which accounts for the hyperbolic character of the power-duration curve. Factors which speed VO2 kinetics in this domain reduce the excess VO2 mechanism and lead to improved exercise performance. We have demonstrated that, in addition to appropriately designed training regimens, induction of a metabolic acidosis prior to exercise speeds VO2 kinetics at high work rates, reducing the increase in both [lactate] and [H+]a and reducing the CO2 load to ventilation during the transient phase of the work. The optimum procedure for inducing these improved pulmonary gas exchange kinetics, however, remains to be determined. PMID- 1642717 TI - Possible mechanisms of oxygen uptake kinetics. AB - The VO2 response to a step change in work rate resembles a first order exponential function. This suggests that a single site of the many which link ATP demand to VO2 is limiting. The location of this site is controversial. Some authors suggest that O2 delivery regulates the VO2 response. Others have suggested that peripheral mechanisms within the active muscle regulate O2 consumption. The evidence supporting each hypothesis is reviewed. It is concluded that O2 delivery sets the initial parameters and peripheral mechanisms then regulate O2 utilization within the bounds initially established by delivery mechanisms. PMID- 1642718 TI - Behavior of cardiac output during progressive exercise tests: a preliminary report. AB - The behavior of cardiac output (Q) during progressive incremental exercise tests was studied in young healthy men. Q approached a plateau and leveled off at almost the same work rate at which oxygen uptake (VO2) attained its maxima, while heart rate (HR) still continued to rise. This suggests that the limiting factor for maximal aerobic capacity in healthy subjects is Q. The rate of increase in Q and HR accelerated from a work rate which is close to the ventilatory anaerobic threshold (AT). The prime cause of the progressive augmentation in cardiac activity is probably an accelerated release of plasma catecholamine and/or potassium. There is a possibility that these substances might also affect the AT. PMID- 1642719 TI - Transient responses of heart rate, skin and muscle sympathetic nerve activity before and after anticipatory muscle contraction. AB - Sympathetic nerve activity leading to skin (SSA) and skeletal muscle (MSA) and heart rate were measured before and during two-minute static handgrip (SHG) in seven healthy volunteers. Two different situations were set before commencement of the exercise; one was that a preparation time of between 4 and 6 minutes was set prior to SHG while no information of starting time for exercise was given to the subjects (Cond. 1). Another was that after two minutes of control rest, countdown was started two minutes before SHG and then the handgrip was started (Cond. 2). Heart rate for 10-s before SHG in Cond. 2 increased significantly from the control value, while there was no significant change in Cond. 1. The magnitude of heart rate response to SHG was the same in either condition. Although SSA for 10 seconds just before the exercise did not show any change from the control value in Cond. 1, it increased in Cond. 2. There was no difference in SSA response patterns during SHG in either condition. Before commencement of SHG, MSA was suppressed at 10-s before exercise from the control value in Cond. 2, but there was no significant change in Cond. 1. After onset of contraction, MSA was suppressed in the brief initial period regardless of countdown, thereafter MSA increased time-dependently. The MSA response pattern to SHG was almost identical in both conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642720 TI - Muscle metabolism during repeated exercise studied by 31P-MRS. AB - We studied 31P-nuclear magnetic resonance spectroscopy (31P-MRS) for repeated non invasive measurement of changes in the muscle metabolites, i.e., creatine phosphate (PCr) and inorganic phosphate (Pi), and changes in intramuscular pH, during repeated exercise and intervening rest periods. Six healthy male subjects performed 2 min of femoral flexion exercise at 20 kgm/min in a 2.1 Tesla superconducting magnet with a 67 cm bore. This exercise was repeated 4 times with 2-min rest periods between bouts. During this time 31P-MRS data was collected with 32 scans per spectrum, requiring 12.8 sec. During exercise, the PCr decreased to 30.3 +/- 7.0% (mean +/- SD) of the pre-exercise level, and it did not completely recover during the rest period (79.0 +/- 1.3% of the pre-exercise level). Thereafter, when the exercise was repeated, the lowest PCr value during exercise decreased gradually (2nd bout, 22.1 +/- 3.9%; 3rd bout, 16.7 +/- 3.2%, and 4th bout 14.9 +/- 3.5%). The Pi increased by 705-740% during exercise and there were no significant differences in maximum Pi among the 4 bouts. During the rest period after the first bout, Pi fell to about 10% below the pre-exercise level in four of the six subjects. With repeated exercise, this undershoot was less common. The Pi/PCr ratio during exercise increased linearly over time. Furthermore, the maximum Pi/PCr ratio during exercise increased significantly with repeated exercises. We conclude that as exercise is repeated PCr gradually decreases, but there is no cumulative increase in Pi. Thus, the Pi/PCr ratio, an indicator of free ADP, increased with repeated exercise. PMID- 1642721 TI - Blood flow during muscle contraction and relaxation in rhythmic exercise at different intensities. AB - Effect of contraction force on blood flow during the contraction and relaxation phase of rhythmic handgrip exercise was studied on 6 healthy women. Velocity of blood flow in the brachial artery and the diameter of the artery were studied by Doppler-ultrasound method. Both the peak and mean velocity of the blood flow were significantly higher during the relaxation period than during contraction, and the velocity during the relaxation period was significantly higher in 30% MVC exercise than in 10% MVC exercise. However, no significant differences were found in the diameter of the artery between resting and exercise conditions, nor between exercises at different intensities. Thus blood flow during the relaxation phase was significantly increased from 135.7 +/- 18.2 ml.min-1 (10% MVC) to 182.5 +/- 19.6 ml.min-1 (30% MVC) by an increased contraction force, whereas blood flow during the contraction phase was hardly affected by increased contraction force. PMID- 1642722 TI - Increase in neuromuscular activity and oxygen uptake during heavy exercise. AB - In order to examine the contribution of neuromuscular activity to the slow increase in VO2 during heavy exercise, integrated electromyogram (iEMG) of dominant working muscle and VO2 was compared in seven subjects during constant load cycling exercise at the intensity of 10% below and 30% above ventilatory threshold (VT) for seven minutes. VO2 and iEMG after 4th min in above VT test was significantly correlated (r = 0.53, p less than 0.01) and VO2/iEMG was constant after 4th min, indicating coupling of iEMG with VO2. The results suggested that the slow increase in VO2 during heavy exercise may result from the changes in the recruitment pattern of motor units. PMID- 1642723 TI - Ventilatory capacity and exercise-induced arterial desaturation of highly trained endurance athletes. AB - Recent evidence suggested that exercise-induced arterial O2 desaturation may occur in highly trained endurance athletes. So, Dempsey brought the hypothesis that the pulmonary capacity for oxygen transport cannot meet superior demands imposed by cardiovascular system in highly trained endurance athletes, and endurance training primarily causes adaptation in the skeletal muscles and in the systemic cardiovascular system, with little change in the pulmonary system. In the present study, we determined the propriety of the hypothesis due to measure the ventilatory capacity of endurance athletes. Sixteen highly trained endurance athletes (ET) and thirteen untrained subjects (UT) volunteered to participate in these experiments. All subjects performed the four experiments, 1) the highest oxygen uptake (peak VO2) during incremental cycle exercise and ventilation (VE), ventilatory equivalent for O2 (VE/VO2) and arterial O2 saturation (SaO2) at which peak VO2 was observed, 2) the maximal voluntary ventilation for 30 sec at rest (MVV), 3) the pulmonary diffusing capacity for CO (DLCO) and expressed per unit of alveolar lung volume (KCO) at rest by the single breath method, and 4) the ventilatory response to hypercapnia (S) at rest by rebreathing method, were measured. The peak VO2 of ET (66.7 ml.min-1.kg-1) was significantly (30.8%) higher than UT (52.4 ml.min-1.kg-1), and VE/VO2 and SaO2 of ET (29.3 and 93.7%, respectively) were significantly lower than UT (34.6 and 95.8%). There were no differences in VE, MVV, DLCO, and S between two groups. PMID- 1642724 TI - Swimming physiology. AB - Swimming takes place in a medium, that presents different gravitational and resistive forces, respiratory conditions and thermal stress compared to air. The energy cost of propulsion in swimming is high, but a considerable reduction occurs at a given velocity as result of regular swim training. In medley swimmers the energy cost is lowest for front crawl, followed by backstroke, butterfly and breast-stroke. Cardiac output is probably not limiting for performance since swimmers easily achieve higher values during running. Maximal heart rate, however, is lowered by approx. 10 beats/min during swimming compared to running. Most likely active muscle mass is smaller and rate of power production lesser in swimming. Local factors, such as peripheral circulation, capillary density, perfusion pressure and metabolic capacity of active muscles, are important determinants of the power production capacity and emphasize the role of swim specific training movements. Improved swimming technique and efficiency are likely to explain much of the continuous progress in performance. Rational principles based on improved understanding of the biomechanics and physiology of swimming should be guidelines for swimmers and coaches in their efforts to explore the limits of human performance. PMID- 1642725 TI - Validity of ratings of perceived exertion as an index of exercise intensity in swimming training. AB - The validity of ratings of perceived exertion (RPE), proposed by Borg (1962), as an index of exercise intensity in swimming training was discussed based on the following four experiments. Experiment I: VO2 and heart rate (HR) were measured and RPE was asked in ten female and seven male physical education students with different levels of swimming skill performing submaximal and maximal work in tethered swimming. The increases in HR and RPE with increase in %VO2max were fitted well by straight lines with high correlation coefficients of r = 0.957 0.999 and r = 0.893-0.988, respectively. RPE was increased in a linear fashion with increase in HR except for a few subjects. The correlation coefficients for linear regression for individuals were 0.862-0.987. Experiment II: Swimming velocity and HR were measured in four groups with different levels of swimming skill. The breast stroke in a 50-m pool for 5 min at three RPE ratings, i.e., very light (RPE 9), somewhat hard (RPE 13) and very hard (RPE 17) was requested of these groups. In good skilled well trained college swimmers, %HRmax was fairly higher than the RPE at the RPE 9 and RPE 13 levels but coincided with the RPE at the RPE 17 level. In skilled trained physical education students, the HR increased with a corresponding increase in RPE. But in the group with low or lower levels of swimming skill, the HR kept about the same values in spite of the increase in RPE. Experiment III: Two male and six female low skilled physical education students took the swimming training in the swimming pool for 2.0-2.5 hours a day, 6 days a week, for 2 weeks. The students also received the swimming training in the sea which lasted for 2 hours each in the morning and in the afternoon for 6 days. The same RPE test, as mentioned in Experiment II, was done before, during and after swimming training. Mean swimming velocity during and after training was slightly higher than that before training at the RPE 9 and RPE 13 levels, and was much higher at the RPE 17 level. Before training, the HR was fairly higher than the RPE at the RPE 9 and RPE 13 level. But during and after training, the HR was much closer to the RPE at the RPE 9 and RPE 13 levels. Experiment IV: Two male and three female lower skilled middle-aged swimmers performed the same RPE test as mentioned in Experiment II.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1642726 TI - Peak oxygen uptake during arm stroke under a hypobaric hypoxic condition. AB - The purpose of this study was to examine the limiting factor for swimming by measuring peak oxygen uptake (peak VO2) during front crawl (C) and arm stroke (A) under a hypobaric hypoxic condition. Seven-trained swimmers (age; 19-21 yrs, 100 m free style event; 57.2 +/- 2.5 secs) were measured twice under a normal (N) (751 mmHg) and a hypobaric hypoxic (H) (602 mmHg) condition in a chamber where atmospheric pressure was regulated. Water flow rate started at 0.80 m.sec-1 and was increased by 0.05 m.sec-1 every 2 min up to 1.00 m.sec-1. Subsequently, flow rate was increased by 0.05 m.sec-1 every minute until exhaustion. VO2 was measured with an automatic analyzer. The peak heart rate under N was not significantly different from that under H in both C (N; 190 +/- 9, H; 184 +/- 6 beats.min-1) and A (N; 180 +/- 6, H; 181 +/- 6 beats.min-1). Peak VO2 values during A (N; 3.42 +/- 0.27, H; 3.08 +/- 0.19 l.min-1) were significantly lower by 15-20% than those during C (N; 4.18 +/- 0.18, H; 3.65 +/- 0.11 l.min-1) for both N and H (p less than 0.01). Peak VO2 values under H were significantly lower than those under N during both C and A (p less than 0.01). There was no significant difference in the magnitude of decrease in peak VO2 between C (12.0 +/- 3.4%) and A (9.8 +/- 3.8%) under H. This ratio of decrease agrees with previous investigations that studied centrally limited exercise, such as running and cycling, under similar levels of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642727 TI - Difference of physiological responses to swimming and running. AB - The purpose of this research is to investigate the range of response to the treadmill running and swimming. Cardiovascular changes and substrates changes in blood were examined before and after healthy male subjects (swimming group (SG) has swimming habits and running group (RG) has practiced basketball or baseball or running more than four days a week) swam and ran for 10 to 15 minutes voluntarily. Average heart rate was recovered more quickly in case of running than swimming in the RG, but in the SG there was no difference. Diastolic blood pressure recovered to the rest condition faster in the SG than RG. In case that subjects have done familiar exercise, free fatty acids increased a little more after 10 minutes than in case of unfamiliar exercise. These results suggest that response of habitual exercise showed lesser change of diastolic blood pressure and more increase of free fatty acids. There might be a difference in physiological responses between usual sports and other kinds, so that we had to be careful when we apply different styles of activity to use training. PMID- 1642728 TI - Validity of critical velocity as swimming fatigue threshold in the competitive swimmer. AB - The purpose of this investigation was to determine whether the critical velocity (CV) as the swimming speed which can be theoretically maintained for a very long time without exhaustion could be applied to estimate the swimmer's endurance performance. CV was based on the concept of critical power originality established by Monod and Scherrer (1965) and extended by Moritani et al. (1981), and expressed as the slope of a regression line between swimming distance (D) at each velocity and its sustained time (T). Seventeen highly trained swimmers were instructed to swim the four different swimming distances (50 m, 100 m, 200 m and 400 m) at maximal effort using the swimming pool. In the results of CV, the regression relations between D and T were expressed in the general form, D = a + bxT, with r2 showing higher than 0.997 (p less than 0.001). These results indicate extremely good lineality. Furthermore, VO2max during incremental exercise test, swimming speed corresponding 4 mM of blood lactate concentration (V-OBLA) and mean velocity in the 200 m and 400 m freestyle (V-200 and V-400) were measured on nine subjects. Significant correlations were found between CV and V-OBLA (r = 0.862, p less than 0.01), CV and V-200 (r = 0.781, p less than 0.01), CV and V-400 (r = 0.999, p less than 0.001), V-OBLA and V-400 (r = 0.869, p less than 0.01) and V-200 and V-400 (r = 0.776, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642729 TI - The physiology of cycling with reference to power output and muscularity. AB - The maximal average power output (Wmax) and capacity (Wcap) of the short-term (anaerobic) energy processes are examined in cyclists and young adults with respect to body size and muscularity. The results show that when Wmax and Wcap are standardized for muscle size the power and capacity of the anaerobic mechanisms are similar between trained sprint and pursuit cyclists and untrained young healthy adults. Thus the efficiency of anaerobiosis appears to a function of muscularity in man over the range of subjects studies. From the data it is estimated that the probable efficiency of supra maximal cycling is of the same order (0.22) as found for steady state submaximal (aerobic) exercise. PMID- 1642730 TI - Muscle energetics during exercise by 31P NMR. AB - Previous studies have shown that a decrease in muscle tension is not proportional to decrease in the ATP concentration and free energy for ATP degradation but is proportional to the decrease in ATP consumption during muscle contraction, and that the free ADP concentration in the cell can be estimated using the Pi/PCr ratio obtained by 31P NMR. From this view, we discuss findings on muscle energetics during exercise that have been clarified by 31P NMR and its future problems. PMID- 1642731 TI - Muscle metabolism during exercise: anaerobic threshold does not exist. AB - Blood lactate level begins to increase at a certain work load or oxygen consumption which is called as anaerobic threshold (AT). However, numerous studies showed that anaerobic glycolysis is not the cause of the enhanced accumulation of blood lactate during exercise. Increased lactate production is seen even in fully aerobic muscles. Some studies suggest that elevation of lactate is due to a temporary imbalance between the rates of pyruvate formation by aerobic glycolysis and pyruvate utilization in the Krebs cycle. These results clearly suggest that AT does not exist. PMID- 1642732 TI - Relationship between power spectral densities of P-P and R-R intervals. AB - To investigate the role of the peripheral effector for the generation of heart rate variability, the relationship among the P-P, R-R, P-R, and R-P intervals were compared on five healthy male subject in the supine position. During supine rest, electrocardiogram was monitored, and P-P, R-R, P-R, and R-P intervals were measured. Power spectral densities (PSD) were estimated by using direct method for successive 256 intervals. PSDs were integrated at the low (PSDLF; 0.05-0.15 cycle/beat) and high (PSDHF; 0.20-0.40 cycle/beat) frequency bands. Mean interval times of P-P, R-R, R-P, and P-R intervals were 827 +/- 40, 827 +/- 40, 357 +/- 34, 170 +/- 19 msec, respectively. PSDLFS of P-P, R-R, R-P, and P-R intervals were 15677 +/- 2771, 15566 +/- 2815, 15345 +/- 2767, 1491 +/- 255 msec2/c/b, respectively. PSDHFS of P-P, R-R, R-P, and P-R intervals were 13289 +/- 3602, 12918 +/- 3897, 12558 +/- 3630, 2758 +/- 517 msec2/c/b, respectively. The PSD of P-R intervals showed white noise. These results might suggest that the periodic fluctuation would be formed at or above the sinoatrial node. PMID- 1642733 TI - Cardiac autonomic regulation after moderate and exhaustive exercises. AB - The purpose of this study was to investigate the recovery kinetics of cardiac autonomic regulation after acute exercises related to exercise intensity. Firstly, eight healthy subjects performed two kinds of constant load exercises at the work rate corresponding to 20% and 100% of the individual ventilatory threshold (VT) in addition to the exhaustive incremental exercise using a cycle ergometer. Blood pressure (BP) and oxygen uptake (VO2) were measured during 9 to 10 min after the exercises as well as the beat-by-beat recording of R-R intervals. Coarse graining spectral analysis (CGSA) was applied to heart rate variability (HRV) data sets of 5 min before exercise, last 5 min during exercise, and 8 to 10 min after exercise. The low frequency (0-0.15 Hz; LO) and the high frequency (0.15-0.5 Hz: HI) areas under power spectra were calculated for evaluating sympathetic (LO/HI) and vagal (HI) activities. The recovery for 10 min was sufficient to settle both VO2 and BP even after the exhaustion. Comparing to the pre-exercise value, however, HI was still suppressed until 10 min after the 100% VT exercise (522 +/- 300 vs. 122 +/- 63 msec2, p less than 0.05) while it was recovered at 10 min after the 20% VT one (353 +/- 122 vs. 487 +/- 159msec2). Secondly, six healthy subjects performed an incremental cycle exercise until exhaustion. The R-R intervals were monitored beat-by-beat during 30 min after exercise. The CGSA was applied to every five min data set of HRV during recovery phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642734 TI - Effect of DCA administration or endurance training on lactate metabolism in mice during and after exercise. AB - The purpose of this study was to investigate the effect of the activation of tissue oxidative capacity by dichloroacetate (DCA) administration or endurance training on oxidative removal of lactate, which is the major pathway of lactate metabolism, in mice during prolonged exercise and after supramaximal exercise. DCA administration significantly decreased the blood lactate concentration and activated the oxidative removal of lactate during prolonged exercise. DCA administration did not change lactate metabolism in mice after supramaximal exercise. Endurance training significantly decreased the blood lactate concentration during prolonged exercise and also activated the oxidative removal of lactate. Endurance training significantly increased the recovery of the blood lactate concentration after supramaximal exercise, while it did not activate the oxidative removal of lactate. These results suggest that the activation of the tissue oxidative capacity decreases the blood lactate concentration and also can activate the oxidative removal of lactate during prolonged exercise, while it does not activate the oxidative removal of lactate after supramaximal exercise. PMID- 1642735 TI - Dose/response effects of exercise modeled from training: physical and biochemical measures. AB - This study has measured the pattern of elevated serum enzyme activity (ESEA) during extended daily training in a dose-response manner and compared ESEA to the pattern of accumulated fitness and fatigue predicted from a mathematical model previously described. Blood samples were taken regularly during the study from each subject and the activity of lactate dehydrogenase (LDH), creatine kinase (CK), and aspartate aminotransferase (AST) in the serum was measured. Although no single physiological/biochemical correlate of the hypothesized fatigue compartment of performance is firmly identified it is significant that the pattern of variation of model fatigue and ESEA throughout training were similar although slightly out of phase. With continued hard training, model fatigue began to plateau and concomitantly ESEA declined exponentially from its initial high value in early training. During relative rest throughout a tapering period following training both ESEA and fatigue reverted quickly towards baseline and follow the similar but earlier time course in blood of a degradative membrane enzyme phospholipase A2 observed in clinical studies. PMID- 1642736 TI - The effects of resistance training on muscle area and strength in prepubescent age. AB - The purpose of this study was to determine the effect of strength training in prepubescent boys and girls on muscle strength and cross-sectional area of upper arm. Subjects were ninety-nine healthy elementary school children who belonged to 1st, 3rd and 5th grades and they were assigned to two groups of training (N = 52) and control (N = 47). Training group participated in strength training program for 12 weeks which consisted of maximum sustained isometric contraction of elbow flexion for ten sec, whereas control group did not participate in special training program in this period. In orger to determine the changes due to training, cross-sectional areas of the tissues in upper arm, such as muscle, fat and bone, were measured by the ultrasonic method. Maximum isometric and isokinetic muscle strength of elbow flexion and extension were measured by means of isokinetic cybex dynamometer. In order to assess the development of physiological maturity, TW2 method was used to estimate the skeletal age in each subject by taking the hand-wrist X-ray photograph. After 12-week training period, the whole cross-sectional areas increased in both training and control groups. This increment was due to significant increases in muscle and bone area in the training group and, on the other hand, due to the increase in fat area in the control. The increment of muscle area of training group was about 50% of that derived from the study on adults (Fukunaga, T., 1978). The increment in cross sectional area of muscle with training was significantly correlated with the skeletal age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642737 TI - The benefits of the low intensity training. AB - This presentation addressed the researches concerning the effects of the low intensity training on health promotion done in our laboratory. Supervised physical training performed at 50% VO2max or lactate threshold for 60 minutes, 3 or 5 times a week for 30 sessions could induce the improvement in VO2max, lipid profiles, and augment in cardio-pulmonary baroreflex. This training was also applied for patients in ischemic heart disease, hypertension, and obesity. These patients could improve their aerobic work capacity. Hypertensive patients could reduce their blood pressure in association with modulating in humoral factors without changes in body weight and diet. The obese patients succeeded in significant body reduction with mild food reduction. We also found the existence of break-point of double product (BPDP) during graded exercise test corresponding to lactate threshold. BPDP will be able to use for estimating lactate threshold. This low intensity training, which is easier and safer, can be recommended to the wide-variety of persons including older person to promote health. PMID- 1642738 TI - The clearance rate of exercise-elevated blood lactate following physical training. AB - In this paper, previous studies regarding the effect of physical training on the disappearance rate of blood La during recovery after strenuous exercise have been briefly summarized. The results of our own recent study of this problem have also been added. It may be concluded that there is some evidence for an improved lactate metabolic clearance rate resulting from physical training in human subjects, when the degradation rate is estimated from serial blood samples taken during a standard ramp ergometer test to exhaustion during each week of a training/detraining sequence. This beneficial effect of training, however, may also be influenced by the initial physical status of the subject and the nature of the training program. PMID- 1642739 TI - Changes in intracellular pH of muscle during dynamic contraction. PMID- 1642740 TI - Liberal arts in the surgery residency. PMID- 1642741 TI - [Therapeutic possibilities of sympathoadrenergic reactions during general anesthesia using sublingual application of glycerol trinitrate]. AB - Strong surgical stimulation (for e. g. sternotomy, mediastinal preparation and aortic dissection in heart surgery) leads to an adrenergic reaction with the so called haemodynamic break-through phenomenon. The inhibition of this reaction by means of narcotics is always connected with a dangerous decrease of cardiac index. Therefore, the sublingual application of nitroglycerin (GTN: 7 micrograms/kg), well established in the therapy of angina pectoris, was used as a rapidly applicable alternative. Patients with coronary heart disease under neuroleptanaesthesia (n = 10) were investigated in comparison to volunteers (n = 5). Beside the registration of haemodynamic parameters by invasive monitoring, the determination of arterial plasma concentrations of GTN and its metabolites 1.2- and 1.3-glyceryl dinitrate (GDN) were performed using gas-chromatographic technique. Using the same doses the haemodynamic changes are more marked and of longer duration in the anaesthetised patients than in the awake volunteers. The cause seems to be the higher and longer detectable active concentrations of GTN and GDN (the average maximum GTN concentrations greater than 0.5 ng/ml still after 12 minutes in contrast to 7 minutes). After discussing various different pharmacokinetic possibilities this effect is probably related to the simple fact of an improved resorption of the drug in the anaesthetised patient (no salivation, no swallow movements). On the basis of this investigation the sublingual application of GTN is a very useful therapy for the blockade of sympathoadrenergic reactions under anaesthesia, but the commonly used doses of GTN has to be reduced by half (3-4 micrograms/kg). PMID- 1642742 TI - Automated anaesthesia recording system. Statement regarding the article by J.S. Gravenstein. PMID- 1642744 TI - Toxic oil syndrome. Current knowledge and future perspectives. Introduction. PMID- 1642743 TI - Physiology, pathophysiology and pharmacology of the coronary circulation with particular emphasis on anesthetics. AB - The normal control of coronary blood flow is through alterations in the resistance of the intramyocardial arterioles (R2). Myocardial cellular hypoxia causes increased breakdown of ATP (or decreases synthesis) resulting in increased concentrations of the purine metabolite, adenosine. This potent endogenous, vascular smooth muscle relaxant vasodilates the R2 arterioles increasing coronary blood flow and myocardial O2 delivery. This mechanism autoregulates coronary blood flow according to myocardial O2 needs. Myocardial hypertrophy (from chronic hypertension) or coronary atherosclerosis interfere with this process and result in myocardial ischemia which may cause symptoms (angina), signs (ECG changes, regional muscle dysfunction) or tissue death (myocardial infarction). In addition, coronary atheroma disrupt endothelial function in the large R1 coronary arteries predisposing to vasoconstriction, platelet aggregation and thrombosis. Therapeutic measures for controlling ischemia may include decreasing oxygen demand (especially heart rate) and maintaining supply (R1 vasodilators and anti thrombotic drugs such as non-steroidal anti-inflammatories). Intravenous, most inhalational and regional anesthesia appear to interfere minimally in the control of both the normal and ischemic coronary circulation. Thus optimizing myocardial oxygen balance (maintaining supply and decreasing demand) during anesthesia protects the ischemic myocardium. High doses of isoflurane, sevoflurane or desflurane are potent R2 coronary vasodilators which may cause redistribution of collateral blood flow away from ischemic regions (coronary steal). However, if tachycardia and hypotension are avoided, such an effect has not been shown experimentally or clinically. Preliminary evidence suggests that halothane may preferentially dilate R1 arteries and/or interfere with platelet aggregation. If these effects are confirmed, then halothane may prove to be the anesthetic of choice in the non-failing ischemic heart. PMID- 1642745 TI - Immunology. PMID- 1642746 TI - Future research. PMID- 1642747 TI - Clinical findings. PMID- 1642748 TI - Pathology. PMID- 1642749 TI - Epidemiological studies. PMID- 1642750 TI - Experimental studies. PMID- 1642751 TI - Chemical composition of TOS-related oils. PMID- 1642752 TI - Histamine: an early messenger in inflammatory and immune reactions. AB - The local concentration of histamine at sites of inflammation and immune responses is invariably high. Recent studies suggest that the biological relevance of this accumulation of histamine extends beyond its well-characterized role in mediating allergic reactions. In this article, Andras Falus and Katherine Meretey describe a possible function for histamine in cytokine-governed regulation of inflammatory and immune cascades. PMID- 1642753 TI - Slow bacterial infections or autoimmunity? AB - In this article, Graham Rook and John Stanford propose that a group of idiopathic diseases that are often associated with a degree of autoimmunity and arthritis, including rheumatoid arthritis, inflammatory bowel disease, sarcoidosis and psoriasis, are caused by extremely slow-growing bacteria. They suggest that these diseases are one end of a continuous spectrum caused by related slow-growing genera, which ranges from rheumatoid arthritis, through Takayasu's arteritis and Whipple's disease, to reach the conventional mycobacterioses such as tuberculosis and leprosy. PMID- 1642754 TI - Intermolecular cooperativity: a clue to why mice have IgG3? AB - Mouse IgG3 subclass antibodies predominate in humoral responses to bacterial polysaccharide antigens. The reasons for this isotype restriction are not fully understood. Here, Neil Greenspan and Laurence Cooper propose that intermolecular cooperativity, a novel mechanism of antibody binding, may help to explain the preferential expression of IgG3 antibodies in these responses. PMID- 1642755 TI - Poly's lament: the neglected role of the polymorphonuclear neutrophil in the afferent limb of the immune response. AB - The polymorphonuclear leucocyte (PMN) has traditionally been thought to participate in the inflammatory response only as an effector cell. However, recent data demonstrate that PMNs can synthesize and release cytokines, such as IL-1, TNF-alpha and IL-6, and hence modulate both T- and B-cell activities in the evolution of an immune response. PMID- 1642756 TI - Intracellular transport of MHC class II molecules. AB - MHC class II molecules associate, during biosynthesis, with peptides derived from endocytosed antigen. Here, Jacques Neefjes and Hidde Ploegh describe the intracellular transport of MHC class II molecules and its relationship to the binding of peptides in endosomal compartments. They discuss alternative routes for the delivery of antigen to sites at which peptides associate with MHC class II molecules and raise the possibility of cell type-specific differences in the handling of MHC class II molecules, and hence in antigen presentation. PMID- 1642757 TI - Observations on constitutional resistance to infection. AB - The attention of most immunologists is held by the elaborate nonspecific and antigen-specific mechanisms of reactive immunity. There is, however, a more fundamental level of immunity to infection that is shared by all forms of life: constitutional resistance to infection. In this article, the nature and importance of constitutional immunity is illustrated using examples from population, cell and molecular biology. PMID- 1642758 TI - Behring's discovery of diphtheria and tetanus antitoxins. PMID- 1642759 TI - Tat and Kawasaki disease. PMID- 1642760 TI - The rheumatoid synovium: a model for T-cell anergy? PMID- 1642761 TI - [Role of the HLA system in the functioning of the immune system]. AB - HLA molecules share a particular architecture that allow them to present various peptides. They belong to 2 different subfamilies (class I and class II) working in parallel: each class restricts the presentation of potentially immunogenic peptides to a peculiar T cells subpopulation. This lead HLA system to be one of the possible components of the allergic background. PMID- 1642762 TI - [Diversity of antigenic fractions of allergenic extracts and importance of the Western blot technique]. AB - The Phast-system groups together the techniques of electrophoresis and transfer. When applied to allergen extracts it allows identification of the allergenic protein fractions and shows their reactivity against sera from allergic patients. The Phast-system is indicated for the choice of the appropriate allergen for specific immunotherapy. If it is not possible to do it systematically, it should be done whenever there is a check to specific immunotherapy. PMID- 1642763 TI - Do burn patients have a silver lining? AB - Silver-containing pharmacological preparations have been used for many years in the prophylaxis and management of burn wound sepsis and, more recently, 1 per cent silver sulphadiazine cream (SSD) has been the treatment of choice for such problems. A prospective clinical study has been undertaken to determine the absorption and effects of the silver ion from SSD, with particular reference to hepatic and renal function. Twenty-two patients were studied. The silver assay was done by atomic absorption spectrophotometry with an attached graphite furnace. The detection level was 0.5 micrograms/l. The precision at 3.5 micrograms/l was 4.8 per cent and at 8.5 micrograms/l was 2.8 per cent. Silver was rapidly absorbed through the burn wound and serum silver levels were elevated in 20 patients. Silver was found to be deposited biochemically and electronmicrographically in the liver and kidneys of the only patient who died in the study group. Early hepatic dysfunction was present in all burns greater than 10 per cent total body surface area. Liver and renal function tests did not correlate with serum silver levels. A urinary threshold to silver excretion was seen at a serum silver level of 100 micrograms/l. This study demonstrates that silver is rapidly absorbed through burn wounds, is deposited in large amounts throughout the body but appears safe when used in the treatment of moderate burns. Whether the very high levels recorded in the subject who died were inherently detrimental will remain a matter for speculation. PMID- 1642764 TI - Neopterin plasma levels in burn patients. AB - Burn victims have severely depressed cellular immunity and despite careful hygiene, antibiotics and early surgical therapy the infection rate remains high. The assessment of plasma neopterin levels can be considered as an indirect measurement of macrophage function, because activation of macrophages is accompanied by the release of D-erythro-neopterin. The influence of burn trauma on neopterin levels was investigated to determine whether neopterin estimations might have a prognostic or diagnostic value. Twenty patients with a mean age of 36 +/- 16 years and a TBSA of 45.5 per cent +/- 23 were studied. During the whole hospital treatment daily blood samples were analysed for neopterin levels using radioimmunoassay. Starting from normal levels (9 +/- 1.6 nmol/l), neopterin content increased continuously until day 10 (30-40 nmol/l), then fluctuated around these high levels for several weeks. There were no differences between patients with TBSA less than 35 per cent or greater than 35 per cent, and between survivors and non-survivors. Burn injury caused a constant increase of plasma neopterin indicating an intact reaction by macrophages. It can be used as an additional parameter for the diagnosis of sepsis: high values being a sign of adequate reaction by macrophages, whereas low neopterin values in the presence of bacteraemia and clinical symptoms of sepsis show a deleterious impairment of immune functions. PMID- 1642765 TI - The psychological problems of burned patients. The Rudy Hermans Lecture 1991. PMID- 1642766 TI - An algorithmic approach to the management of cutaneous burns. AB - An algorithm of fluid resuscitation for cutaneous burns is presented. The management of these cases entails an initial process of evaluation followed, when appropriate, by the administration of intravenous fluids. The fluid requirements are prospectively calculated and subsequently modified by using closed loop feedback with monitoring of urine output, plasma deficit, osmolality and vital signs. Three 'problem boxes' have been incorporated into the algorithm to outline the management of: 1. fluid deficit and excess; 2. acute renal failure; 3. the critically ill patient. An algorithm such as this can never be complete, but in its present form it provides both a teaching tool for junior staff as well as a valuable clinical aid for those involved in the acute management of burns patients. PMID- 1642767 TI - Factors involved in burn mortality: a multivariate statistical approach based on discriminant analysis. AB - This article suggests an alternative statistical model for studying the mortality of burned patients: discriminant analysis. This model was applied to our population of 532 patients among whom 71 died. It is not the first time that this model has been applied to assess burn mortality, although it is not frequently used for that application. We found four factors that are statistically significant: age, TBSA, inhalation injury and sex (female). Discriminant analysis allowed us to demonstrate an impressive correlation between death, age and TBSA; inhalation injury by itself and sex, the two other significant factors in our study, seem to have a minor influence on the final outcome of the burned patients and their predictive value is virtually nil. The advantages of this statistical model are compared with logistic regression, the commonly chosen statistical method. PMID- 1642768 TI - Incidence of HIV seroconversion in paediatric burn patients. AB - A retrospective review of paediatric patients treated for acute burn injuries and receiving blood/blood products between 1978 and 1985, identified 52 patients at risk for HIV infection. Over 50 per cent of the identified population had received 3 or more units of blood/blood products during their acute hospital stay. A total of 214 patients (36.8 per cent) have been tested for HIV seroconversions: five tested HIV positive by ELISA and four were confirmed by Western Blot, yielding a 1.9 per cent incidence. The four confirmed patients received 2-9 total body blood volume turnovers during their postburn period in hospital. At 4 years post-exposure, two patients show active disease, one is currently asymptomatic and one has died from AIDS-related sepsis. PMID- 1642769 TI - Operative treatment of deep burns of the scalp and skull. AB - Traditional surgical treatment of deep burns of the scalp and skull involve the excision of necrotic bone and soft tissues with trephanation of the bone to permit granulation tissue formation and subsequent grafting. This approach prolongs wound time, adds additional trauma and, even after initial healing, necessitates secondary soft tissue and bone reconstruction. The treatment described here is an alternate and more aggressive one involving early excision of necrotic soft tissue without bone resection followed by immediate coverage with well-vascularized axial flaps from adjacent intact scalp. This method provides an optimal environment for healing and regeneration of areas of destruction to the skull. This surgical method was used in the treatment of 22 patients with deep burns of the scalp with satisfactory clinical results. Bone regeneration was confirmed by roentgenological investigations. PMID- 1642770 TI - An analysis of childhood burns in Kuwait. AB - A prospective study of 394 burned children (in-patients) up to the age of 12 years old was carried out for the period from January 1984 to December 1986. They were categorized into three age groups, the infants and toddlers 0-2 years, early childhood 3-6 years and late childhood 7-12 years. In the first two groups scalding was the predominant cause of injury, while in late childhood there were many more flame burns. Ninety-five per cent of the accidents occurred at home and the majority happened in the presence of parents. The presence of parents was not a deterrent to the accident but ensured speedy transport to the hospital. In our review 3 per cent of patients sustained more than 50 per cent BSA burns, there were 12 deaths with a mortality rate of 3 per cent. An intense campaign to make parents aware of the risk factors and their avoidance is required to reduce the number of burn accidents. PMID- 1642771 TI - Burn injuries in the Dong Bei area of China: a study of 12,606 cases. AB - This survey analyses data from nine Chinese burn units with respect to age, causes, severity of burn injury, and survival or death of patients admitted to hospital during the past 10 years (from January 1980 to December 1989). Of 12,606 burned patients treated, 3391 were children (26.9 per cent) and over half the children (52.3 per cent) were up to 4 years old. Almost 60 per cent of the 12,606 patients treated were in the young adult group (15-44 years), and 86.9 per cent of 12,606 patients sustained thermal injuries mainly from fire flames followed by scald injuries (40.7 per cent). About 93 per cent of the patients had burns covering less than 50 per cent of the body surface area. The overall mortality rate was 1.24 per cent. The LD50 for the 12,112 patients less than 60 years old was a burned surface area exceeding 80 per cent of the total body surface area. PMID- 1642772 TI - Benefits of silicone cream occlusive dressing for treatment of meshed skin grafts. AB - A side-by-side evaluation of a silicone cream occlusive dressing technique for grafted meshed skin on the extremities of 10 patients is described. The site treated by silicone cream showed less congestion in the interstices of the mesh, less visible diamond pattern, and less hardness of the skin in all patients compared with the control site, which was treated by application of petroleum jelly ointment. The general appearance of the silicone cream-treated site showed better cosmetic results when compared with the control site. PMID- 1642773 TI - In vitro antimicrobial effects of fresh split skin, homologous-cultured epithelium and porcine split skin grafts for wound coverage. AB - Various biological dressings, for example, human fresh and cadaver skin grafts, homologous cultured human epithelium and deep frozen porcine split skin (Lyocutis), have been used to treat skin loss. Each of these biological dressings has its advantages and disadvantages. The antimicrobial properties of each dressing type are important since bactericidal activity influences the lifespan of the transplanted tissue. In the present study the in vitro antimicrobial effects of human fresh skin, homologous cultured epithelium and Lyocutis were compared to in vivo bactericidal activity of these dressings and possible clinical applications are recommended. PMID- 1642774 TI - Prevention of dressing slippage under an elastic bandage. AB - A technique is described to prevent the shift in position of dressing materials by applying a double-sided adhesive tape between the skin and the elastic bandage. This technique also prevents a shift in position of a pressure garment, especially when applied around joints on the extremities. PMID- 1642775 TI - Burns from electric fire-guards. AB - Nine children with burns caused by contact with electric fire-guards are presented. A method of preventing such injuries is recommended. PMID- 1642776 TI - Enteral hyperalimentation of burned patients: the possibility of correcting metabolic disorders by the early administration of prolonged high calorie evenly distributed tube feeds. AB - Metabolic processes and the ways they may be treated were investigated in severely burned patients receiving prolonged high calorie evenly distributed tube feedings. It was shown that in critically ill patients the absorption of nutrients in the upper regions of the intestine was slightly impaired but the ability to absorb was preserved, which made it possible to provide prolonged evenly distributed tube feeding. For these purposes we used the nutrient mixture 'Combustal'. Restoration of nitrogen balance could be reached within about 10 days after starting tube feeding. However, the creatine excretion remained high, a manifestation of increased dystrophy of muscle tissue. Pseudocholinesterase activity in serum was also decreased, suggesting subnormal biosynthetic processes. To provide the full correction to normal of the metabolic processes the tube feeding with 'Combustal' should be given for at least a month. PMID- 1642777 TI - Chemical burns: our 10-year experience. AB - A review of 173 patients with chemical burns admitted to our burn unit was carried out during the years 1976-85. Most burns were work related (83 per cent). The majority of patients were men aged 21-50 years (mean age = 29.6 years). The mean total body surface area involved was 3.6 per cent (range = 1-30 per cent). The mean length of stay in hospital was 6.3 days (range = 1-52 days). The extremities were involved in 68 per cent of the patients. The more common aetiological agents were bromine and its compounds (36 per cent), then acids (21 per cent), alkalis and organic substances (14.5 per cent each). The severest burns were caused by the inorganic substances. Delayed admission was most characteristic of the bromine and alkali burns. Complications included local infection (19 cases), systemic infection (two cases), inhalation injury (two cases), tissue necrosis (one case) and corneal erosion (one case). There were no deaths. Increased awareness of the hazardous potential of chemicals should help reduce the incidence of chemical burns. PMID- 1642778 TI - Management of electrical injuries of the abdomen. AB - High voltage electrical burns may involve intra-abdominal viscera with or without an abdominal wound. The risk of such an involvement is much higher when a wound is present. Depending upon the amount of heat produced vapourization of tissues may occur. If it includes part of the peritoneum, visceral damage is revealed immediately. If it does not occur to that extent, necrosed tissues remain in continuity and visceral involvement remains concealed until slough separates. The prognosis is related to early diagnosis of the associated visceral injury. It is recommended that the debridement should be undertaken at 2-3 days postburn. Laparotomy is indicated if part of the peritoneum is also debrided. Reconstruction of the abdominal wall may be a formidable task. Among the options available, pedicled muscle and musculocutaneous flaps seem to be ideally suited for the purpose. PMID- 1642779 TI - Hot tap water burns. PMID- 1642780 TI - Role of a two-chain IL-6 receptor system in immune and hematopoietic cell regulation. AB - Three factors with distinct function are involved in the regulation of the B-cell response into antibody-producing cells: (1) a factor for the activation of resting B cells (BSF1/IL-4), (2) a factor for the growth of activated B cells (BCGFII/IL-5), and (3) a factor for the final maturation of B cells into antibody producing cells (BSF2/IL-6). The cDNAs for these three molecules have been cloned, and studies with recombinant molecules demonstrated that their individual functions were not confined to the B-lineage cells; they were found to have a wide variety of biological functions. A typical example of a pleiotropic function of such interleukins is BSF2/IL-6. BSF2/IL-6 is not only a B-cell-differentiation factor, but also is a potent growth factor for myeloma cells. Moreover, BSF2/IL-6 acts as hepatocyte-stimulating factor to induce acute-phase proteins and multicolony-stimulating factor to activate hematopoietic stem cells. It appears that BSF2/IL-6 plays an essential role in the host defense mechanisms against infections, inflammation, and injury. Receptors for BSFs have not yet been molecularly cloned because of the low density of receptor molecules. Recently, the cloning of the cDNA for BSF2/IL-6 receptor has been achieved and its molecular structure and the signals transduced through it are described herein. PMID- 1642781 TI - [Serological screening for Trypanosoma cruzi among blood donors in central Brazil]. AB - The present study compares the results of serological screening for Trypanosoma cruzi infection done at blood banks with results obtained in Chagas' disease studies undertaken by the Reference Laboratory of the Federal University of Goias (UFG) and evaluates the use of the enzyme-linked immunosorbent assay (ELISA) for this purpose. The study was conducted with data from six of the eight blood banks in the city of Goiania in central Brazil, an urban area in which this infection is highly endemic. The population studied consisted of 1,513 volunteers who had donated blood for the first time between October 1988 and April 1989. The sample represented 50% of all first-time blood donors during the period. Of these donors, 94% were residents of urban areas, and of these, approximately 26% had migrated from the countryside. Nearly 90% of the blood donations in the city are received at these banks, which normally use the indirect hemagglutination and complement-fixation tests. The samples selected for the study of T. cruzi antibody in first-time blood donors were assayed at the Reference Laboratory of the Federal University of Goias using the indirect hemagglutination (IH), indirect immunofluorescence (IF), and enzyme-linked immunosorbent assay (ELISA) tests, independently of the serological classification performed by the blood banks. Comparison of the results provided by the latter with the positivity pattern established in the study (IH and IF yielded simultaneous positive results in the Reference Laboratory) revealed a relative sensitivity of 77%, with extremes ranging between 50% and 100%, depending on the blood bank studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642782 TI - [Psychiatric disorders among victims of disasters in Ecuador]. AB - Previous studies in developing countries have demonstrated post-disaster stress disorders in a substantial share of the people living through a natural calamity, but questions have remained as to the severity of these mental health problems. This article reports information derived from a 1987 study of Ecuadorian earthquake victims that shows many of the victims had diagnosable psychiatric disorders and provides insight into the nature of those disorders. PMID- 1642783 TI - Fluorescence spectroscopy studies of the effects of pyrethroids on the DPPC vesicles. AB - The interactions of pyrethroids with membrane lipids have been studied by means of fluorescent membrane probe DPH. Pyrethroids located in the interior hydrophobic regions of the lipid bilayer, differed in their effectiveness of lowering the phase transition temperature and in their ability to broaden the temperature range of this transition. With the increase in the concentrations of pyrethroids, the effects of disordering hydrocarbon packing were increased by pyrethroids. Fluorescence polarizations (P) were decreased in gel state, but not changed in fluid state by permethrin. The pyrethroids containing a cyano substituent could not only disturb the hydrocarbon packing in the bilayer core, but also cause collisional quenching of DPH fluorescence in gel state, P were decreased, then were increased and at last were decreased slightly again as the concentrations were increased, in fluid state P were not changed substantially at low concentrations and were increased obviously when the concentrations were higher. PMID- 1642784 TI - An outbreak of poisoning from Penicillium cyclopium contaminated dried persimmon. AB - It is the first report of an outbreak of 114 food-poisoning cases due to consumption of Penicillium cyclopium contaminated dried persimmon. Gastralgia, diarrhea, dizziness and general malaise are chief symptoms of the poisoning, with incubation period of 2-6 hrs generally and a short disease period (generally recovered within 2-3 days). No enteropathogenic organism, pathogenic coccus and Campylobacter jejuni were detected. Surface fungi counts were 49,000/g, 21.3 times of that discovered in the marketed dried persimmon. Penicillium cyclopium Westling was the dominant fungus isolated. Mouse toxicity tests were carried out with the crude extracts of the fungus culture. Diarrhea, tremor and convulsion were observed before death. During autopsy, necrosis and hemorrhagic foci were observed in G.I. tract after intra-peritoneal injection and intubation. In histo pathological examination, different degree of necrosis and scaling of gastro intestinal mucous membrane, lymphocyte infiltration, and necrosis of liver cells and renal tubule epithelial cells could be seen. PMID- 1642785 TI - Effect of vitamin C supplementations on iron deficiency anemia in Chinese children. AB - A total of 65 children with mild iron deficiency anemia (IDA) were divided into 5 groups, and received 0, 25, 50, 100 and 150 mg/day of vitamin C (VC) respectively every day for 8 weeks. Hemoglobin, serum ferritin, free erythrocyte and hematocrit were determined every week. At a daily average intake of about 30 mg of VC and 7.5 mg of Fe, the results of the study indicate that: (1) VC supplement alone could effectively control children's IDA, and a dose-dependent relationship was observed. (2) 50 mg/day of VC is the most efficient dosage and 6 weeks is the shortest time for an effective therapy. (3) With a diet predominantly comprised of plant foods, it is suggested that appropriate dose of VC should be supplemented for the children during winter and spring in northeastern areas of China. PMID- 1642786 TI - A judgment of attribution of increase in urine beta 2-microglobulin after environmental cadmium exposure. AB - Urine beta 2-microglobulin (beta 2-m) was measured in 433 persons with low-level, long-term environmental exposure to Cd, and in 124 control persons from unpolluted area. In 152 of the exposed persons, and some of the controls, the urine beta 2-m exceeded the limit. Of the 433 exposed persons, 74 cases with both urine Cd and beta 2-m exceeding the limit were matched by the control. This study suggests that after the stratification of the degrees of renal tubular injury according to the fractional beta 2-m excretion (FE beta 2-m) and coordination of clinical examination, FE beta 2-m could contribute to identifying renal tubular dysfunction due to Cd exposure and kidney lesion when both Cd exposure and original nephropathy exist. PMID- 1642788 TI - Altered host resistance to Listeria monocytogenes in mice exposed to 1 chloroacetophenone (CN) vapours. AB - Short term repeated exposure of 1-chloroacetophenone (CN) vapours at a concentration of 0.153 mg per litre for 15 minutes daily on 10 consecutive days in Swiss albino male mice resulted in increased mortality to Listeria monocytogenes. Significantly elevated bacterial growth was observed in the spleen and liver of the CN exposed animals. The increased bacterial count in these organs was evident within 4-6 days post challenge as compared to vehicle exposed infected and unexposed infected animals. Increased susceptibility to infection has been considered to be the function of immune alteration due to cumulative short term effects of CN vapour inhalation. This may be attributed to immunotoxic effects of CN on T-cells mediated macrophage functions. PMID- 1642787 TI - Indoor air pollution and pulmonary function in children. AB - Pulmonary function in winter time in 1,343 school children aged 10-13 years was measured in four cities located in northern and southern part of China. The results showed that FVC, FEV1, PEF, V75, V50 and V25 in children living in homes with coal stoves were decreased by 1.5-10.7% compared with children living in homes with gas or LPG stoves in Chengde and Shanghai. In contrast to this, no significant difference in pulmonary function was found in Shenyang and Wuhan. It suggested that this phenomenon was related to indoor air pollution, and partly related to passive smoking or outdoor air pollution. PMID- 1642789 TI - Development of the new antimalarial drug pyronaridine: a review. AB - This report outlines the structure scheme and development of a new antimalarial drug pyronaridine, which was synthesized from either 2-aminopyridine or pyridine. A series of in vivo and in vitro experimental studies and the assessment of toxicity revealed pyronaridine to be a promising agent against erythrocytic stage of malaria parasites. It exhibited low toxicity and had no cross-resistance to chloroquine. Clinical administration in malaria cases showed high efficacy and mild side-effects. In order to retard the development of resistance of Plasmodium falciparum to pyronaridine, a combination of pyronaridine/sulfadoxine/pyrimethamine was used in the treatment of chloroquine resistant falciparum malaria in Hainan Province. Further in vivo test was carried out to monitor the sensitivity of P. falciparum to this combined formula for 5 years (1986-1990) in Diaoluo area where chloquine-resistant falciparum malaria was prevalent. Drug resistance was not demonstrated in this field study. PMID- 1642790 TI - Studies on the epidemiology and etiology of moldy sugarcane poisoning in China. AB - Moldy sugarcane poisoning, an acute fatal food poisoning of unknown etiology, has occurred in 13 provinces in China. The epidemiological characteristics and clinical features were described. Evidence from laboratory studies indicates that 3-nitropropionic acid produced by the fungus Arthrinium Spp. is the etiological factor of this food poisoning. PMID- 1642791 TI - Acetylcholinesterase characteristics of termite queen exposed to anticholinesterase compounds. AB - A regional profile of AChE activity was noted in the Indian termite queen Odontotermes redemanni with the head recording the higher and body the lower range of activity. The enzyme characteristics such as substrate and temperature optima were more or less similar while pH requirement for optimum AChE activity varied from 7.0 to 7.6 In vitro inhibition of head and body AChE was studied using pure and commercial anticholinesterase compounds. Interestingly, the commercial formulations like Metacid-50 and Carbaryl are potent enough at 1 x 10( 8) M to produce 50% in vitro inhibition of AChE of head and body regions within 15 min of preincubation. A 20 min of preincubation (t0.5) was necessary to record 50% in vitro inhibition of AChE with known and pure anticholinesterase compounds such as DFP (3.5 x 10(-10) M) and physostigmine (3.6 x 10(-10) M). It is surmised that (a) the response of the head and body AChE to the commercial formulations of the insecticides may be used as a reliable and sensitive bioindicator of pesticidal contamination of the terrestrial environment and (b) termite control may be successfully done with the application of organophosphate or carbamate compounds. PMID- 1642792 TI - Role of soluble factors in immune and normal sera in the control of giardiasis due to Giardia lamblia. AB - Hyperimmune sera (HIS), raised against crude giardia antigen, on in vitro interaction, caused more agglutination of Giardia lamblia trophozoites. Heat inactivated HIS possessed a comparable agglutinating activity as the non inactivated controls. Non-inactivated normal (unimmunized) serum caused immobilization of Giardia trophozoite, which was checked on heat inactivation. Antibodies in immune sera are mainly responsible for agglutination, whereas the heat labile non-immune components control the mobility of the intestinal parasite. PMID- 1642794 TI - Removal of Cu and Ni by free and immobilized microalgae. AB - The present investigation evaluated the effectiveness of Chlorella cells in concentrating Cu and Ni in their cells and thereby removing the two metals from solution. The removal efficiency of the two metals by free and immobilized algal cells were further studied. (1) Four types of Chlorella cells, namely Chlorella pyrenoidosa (26) (from Carolina Biological Supplies Company), Chlorella HKBC-1 and-2 (isolated from a polluted stream receiving wastewater from several electroplating factories) and Chlorella HKBC-3 (from a clean water pond) were subjected to different concentrations of Cu and Ni accordingly. It was revealed that Chlorella HKBC-1 was the most tolerant species to Cu and Ni as reflected by their highest values of 48 h and 96 h "Highest no effect concentrations" (The highest concentration of the tested substance that does not inhibit the growth rate of the alga: Cu 2 and Ni 10 mg/l at 48 h, Cu 2 and Ni 5 at 96 h). This was followed by C. pyrenoidosa (26) and then C. HKBC-2 while C. HKBC-3 had the lowest tolerance to the two metals (Cu 0.5 and Ni 2 at 48 h; Cu 0.5 and Ni 1 mg/l at 96 h). (2) It was further revealed that C. HKBC-1 had higher concentration factors and removal efficiencies of Ni (734-963 mg/l, 16.3-18.7%) and C. HKBC-2 had higher concentration factors and removal efficiencies of Cu (2316-2839 mg/l, 53.7 66%) when exposed to lower concentrations of Cu (0.5, 1 and 2 mg/l) and Ni (5, 10 and 13 mg/l). (3) By treating the free and immobilized algal cells (algal cells entrapped in alginate beads) with different concentrations of Cu and Ni, it was observed that free cells had higher concentration factors and removal efficiencies when compared with immobilized cells (free cells: Cu 1577-3056 mg/l, 24.2-71.4%; Ni 355-849 mg/l, 4.8-18.7%; immobilized cells: Cu 453-935 mg/l, 13.9 53.2%; Ni 244-486 mg/l, 3.2-11.9%). PMID- 1642793 TI - Effect of certain toxicants on gonadotropin-induced ovarian non-esterified cholesterol depletion and steroidogenic enzyme stimulation of the common carp Cyprinus carpio in vitro. AB - Isolated ovarian tissues from the common carp, Cyprinus carpio were incubated in vitro to obtain a discrete effect of four common toxicants of industrial origin, namely phenol, sulfide, mercuric chloride and cadmium chloride, on gonadotropin induced alteration of nonesterified and esterified cholesterol and steroidogenic enzymes, delta 5-3 beta-HSD and 17 beta-HSD activity. Stage II ovarian tissue containing 30-40% mature oocytes were shown to be most responsive to gonadotropins in depleting only nonesterified cholesterol moiety and stimulating the activity of both. Safe doses of above mentioned toxicants when added separately to stage II ovarian tissue with oLH (1 microgram/incubation) gonadotropin-induced depletion of nonesterified cholesterol and gonadotropin induced stimulation of the activity of both enzymes was significantly inhibited. Esterified cholesterol remained almost unaltered. Findings clearly indicate the impairment of gonadotropin induced fish ovarian steroidogenesis by the four toxicants separately. PMID- 1642795 TI - Viral aseptic meningitis in the United States: clinical features, viral etiologies, and differential diagnosis. PMID- 1642796 TI - Pancreatic abscess and infected pancreatic pseudocyst: diagnosis and treatment. PMID- 1642797 TI - Approach to the febrile traveler returning from Southeast Asia and Oceania. PMID- 1642798 TI - Management of septic shock: new approaches. PMID- 1642799 TI - The increasing prevalence of resistance to antituberculosis chemotherapeutic agents: implications for global tuberculosis control. PMID- 1642800 TI - Use of immune globulins in the prevention and treatment of infections. PMID- 1642801 TI - Mycobacterium avium complex in AIDS. PMID- 1642802 TI - Aeromonas species: role as human pathogens. PMID- 1642803 TI - Evaluation of cryptic fever in a traveler to Africa. PMID- 1642804 TI - Purulent pericarditis. PMID- 1642805 TI - Diagnosis and management of infections of implantable devices used for prolonged venous access. PMID- 1642806 TI - Familial occurrence of Summitt syndrome or a variant example of Carpenter syndrome? AB - In this report, we describe three sibs presenting an identical malformation syndrome i.e.: acrocephaly, brachydactyly, prominent metopic ridge, broad depressed nasal bridge, narrow maxillae, obesity and normal intelligence. We discuss the relationship between this combination of clinical signs and symptoms most compatible with the diagnosis of Summitt syndrome and the Carpenter syndrome. PMID- 1642807 TI - Apert syndrome with partial preaxial polydactyly. AB - Acrocephalosyndactyly type I or Apert syndrome is characterized by craniosynostosis, particular dysmorphic features and abnormalities of the hands and feet. Rarely, polydactyly of the toes has been reported, and in this event the diagnosis of Carpenter syndrome must be discussed. A case of atypical Acrocephalosyndactyly type I syndrome with partial preaxial polydactyly is reported. Despite this preaxial polydactyly a diagnosis of Apert syndrome consecutive to a new mutation was made, and the possibility of recurrence considered to be highly improbable. PMID- 1642808 TI - Extreme growth failure and kyphoscoliosis as complications of the distal trisomy 10q syndrome. AB - The patient was diagnosed in infancy. Clinical findings and results of re evaluation 13 years after diagnosis are presented. PMID- 1642810 TI - A new syndrome with ptosis, coloboma and mental retardation. PMID- 1642809 TI - A syndrome of mental retardation, short stature, craniofacial anomalies with palpebral ptosis and pulmonary stenosis in three siblings with normal parents. An example of autosomal recessive inheritance of the Noonan phenotype? AB - We present a family with four children in which three, a girl and two boys, present a similar MR/MCA syndrome with slight to moderate mental retardation, short stature, peculiar facies with palpebral ptosis, pectus excavatum and pulmonary stenosis. As both parents are mentally and physically normal, autosomal recessive inheritance of this Noonan-like phenotype is most likely. The findings in the present family confirm that the Noonan phenotype may be caused by different etiologies with different types of genetic transmission. PMID- 1642811 TI - Lethal malformation syndrome in three siblings. A variable expression of the same entity? PMID- 1642812 TI - The check-up of reproductive health and genetic counseling. AB - The Hungarian Family Planning Program was a feasibility study on combining methods of periconceptional care. The first step was the check-up of reproductive health, including family history of the couples, case history of females, pre pregnancy examination (vaginal and cervical smears), and the measurement of basal body temperature, sperm examination, psycho-sexual exploration and exclusion of some risk factors. This preconception screening program was carried out by graduate trainee nurses to identify those participants secondary health services. The data of 4,240 couples attending in the Budapest Center indicated a useful relationship between the check-up of reproductive health and genetic counseling clinics, by selecting couples requiring genetic counseling and preventing other couples making unnecessary visits. PMID- 1642813 TI - Wiedemann-Beckwith syndrome: clinical, cytogenetical and radiological observations in 39 new cases. AB - Thirty-nine patients (82% under 1 year of age) with Wiedemann-Beckwith syndrome (WBS) were prospectively studied. To evaluate the somatometric data the normal range was set out at mean +/- 2 SD. The relevant physical findings were a characteristic face, non increased mean height and weight, normal head circumference, defective abdominal wall, a predominance of the upper segment, and tibial bowing. Mental retardation was documented in 5 cases but in only 1 it was related to hypoglycemia. The 32 cases karyotyped were normal. Since neonatal hypoglycemia is frequent (34.3% in our series) and potentially deleterious for the CNS we propose to monitor the glycemia every 6 h during the first 3 days in WBS newborns in order to correct glycemia below of 2.6 mmol/l (46.8 mg/dl) according to recent studies. The comparison with previous large series enabled us to precise the frequency, onset and evolution of the main stigmata. PMID- 1642814 TI - Smith-Lemli-Opitz syndrome: the changing phenotype with age. AB - In this report we present follow up data of two brothers with Smith-Lemli-Opitz syndrome. The changes with ageing are striking and few of the typical SLO traits are still present, which makes it extremely difficult to make the diagnosis Smith Lemli-Opitz syndrome at adult age. PMID- 1642815 TI - Partial monosomy 8p and partial trisomy 8p with moderate mental retardation. AB - A female patient with mosaicism for partial monosomy 8p and partial trisomy 8p is presented. Her karyotype is 46,XX, del(8)(p21)/46,XX, dup(8)(p21----pter). She showed minimal dysmorphic features, agenesis of the corpus callosum and moderate developmental delay. There is no previous report of mosaicism for partial monosomy and partial trisomy 8p. The clinical findings in the presently described patient are less severe than those reported in cases with only monosomy or trisomy of the distal part of chromosome 8. PMID- 1642816 TI - Tetraphocomelia and bilateral femorotibial synostosis. A severe variant of the thrombocytopenia-absent radii (TAR) syndrome? AB - In this report we describe severe tetraphocomelia with complete femorotibial fusion in a second trimester male fetus. The association of severe tetraphocomelia-femorotibial synostosis has previously been reported in three patients as examples of a severe variant of the thrombocytopenia-absent radii (TAR) syndrome. In the present fetus no morphological abnormalities of the megakaryocytes were detected. This observation is not in favour of the hypothesis that abnormalities of the primordial megakaryocytes may be causally related with the pathogenesis of the limb malformations as present in this syndrome. PMID- 1642818 TI - Outcome measures ... a chimera? PMID- 1642817 TI - Radial ray deficiency and ulnar ray deficiency in two sibs. AB - A kindred with a diabetic mother is described with one sibling with a radial deficiency (type 1 radial dysplasia (Bayne) with a hypoplastic thumb type 3 of Blauth) and one with an ulnar ray deficiency (type 2 of Ogden or type 1 of Swanson). A metabolic cause is probable, although the diabetes was well controlled during pregnancy. PMID- 1642819 TI - Analysis of data in idiographic research. Issues and methods. AB - Time-series and single-subject designs are being advocated for use in rehabilitation research to document the effectiveness of therapeutic intervention procedures. The argument is made that these designs are practitioner-oriented and practice-based. Acceptance and application of single-subject procedures by rehabilitation researchers will depend on the development of reliable and accurate methods of data analysis. Previous research suggests that traditional visual analysis of graphed data is unreliable and that quantitative supplements to visual analysis should be included in single-subject investigations. The advantages and limitations of two commonly advocated supplements to visual analysis are examined. The two supplemental procedures are the split-middle method of trend estimation and the resistant trend line. One advantage of the resistant trend line is that it does not make the assumption of a linear pattern in single-subject data. The argument is made that the resistant trend line is the preferred method and should be selected over the more commonly used split-middle method of trend estimation. The advantages and limitations of other quantitative procedures are briefly examined. PMID- 1642820 TI - Insights into amputee running. A muscle work analysis. AB - Five young, active, unilateral below knee amputees wearing the SACH prosthetic foot, and six normal subjects participated in the study. Subjects ran at a controlled velocity of 2.8 m/s +/- 10% over a ground reaction force plate while being filmed with a video camera. Joint moments, power outputs and mechanical work characteristics were then calculated. During stance phase the amputee prosthetic limb exhibited a marked reduction in total work. There was a reduction in the mechanical work at the knee and the prosthetic foot/ankle with a compensatory increase in mechanical work by the hip musculature. The intact stance phase limb mechanical work characteristics were not significantly different from normal. The hip flexors were the only muscle group in the swing phase prosthetic limb with a significant increase in muscle work compared with normal subjects. The intact swing phase limb in contrast exhibited a marked increase in concentric muscle work by the hip flexors and eccentric muscle work by the knee flexors in early swing phase, and an increase in concentric hip extensor and eccentric knee flexor muscle work in late swing phase. The major compensatory patterns, therefore, that allow below knee amputees to run appear to be an increase in stance phase hip muscle work on the prosthetic limb and increased hip and knee muscle work on the intact limb during swing phase. PMID- 1642821 TI - Estimation of normal lumbar flexion with surface inclinometry. A comparison of three methods. AB - The purpose of this study was to determine the magnitude and clinical significance of surface measurement error in the determination of lumbar spinal flexion. Intrarater, inter-rater and intermethod reliability estimates were obtained using single inclinometry, double inclinometry and back range-of-motion inclinometry methods. Eight healthy subjects were examined independently by two experienced observers and three replicates of each measurement were obtained by each observer in a random sequence. In addition, three replicates of lumbar flexion angles were obtained for each subject by a single observer using the B 200. Reliability estimates were determined by intraclass correlation coefficients and were further compared by paired t tests between observation series. The median range of error was 8.5 degrees using the single inclinometer, 10.5 degrees using the double inclinometer and 16 degrees using the back range-of-motion. The intrarater reliability was generally higher than inter-rater reliability and intermethod reliability was low in most cases reflecting the poor cross-validity across inclinometry methods and between each inclinometry method and the B-200. In conclusion, significant measurement error in estimating lumbar flexion by inclinometry may be expected to occur even in a "controlled" setting using experienced observers, standard examination techniques and asymptomatic healthy subjects. These findings appear to undermine the expectation that the clinician can reliably apply surface inclinometry to estimate loss of spinal mobility for purposes of impairment determination. PMID- 1642822 TI - Sexual activities, concerns and interests of men with spinal cord injury. AB - A representative sample of 79 men with spinal cord injury, drawn from a sampling frame of 661 women and men who reside in the community, was studied in terms of sexual activity, concerns and interests. Participants responded to a questionnaire and rating scales and were physically examined to establish their neurologic status. With respect to eleven other areas of life, sex life ranked the lowest in terms of satisfaction and fifth in terms of importance. Of the sample, 67% reported having had a physical relationship (not necessarily including intercourse) in the past 12 months. Areas of sexual activity about which respondents were most concerned were not satisfying a partner, getting or giving a sexual disease, urinary accidents, and not getting enough personal satisfaction. From among seven topics related to sexuality, the three in which there was greatest interest were methods and techniques to achieve sexual satisfaction, helping a partner cope emotionally with limitations on sexual activity and ability to have children. PMID- 1642823 TI - Outcomes following cardiopulmonary resuscitation in an acute rehabilitation hospital. Clinical and ethical implications. AB - This retrospective study examines cases of cardiac arrest requiring cardiopulmonary resuscitation (CPR) in an acute rehabilitation hospital. All admissions to the Center for Rehabilitation Medicine at Emory University, a 56 bed facility, are reviewed. Seventeen cases of true cardiac arrest are identified for analysis of ultimate disposition over a 10-yr period. Only one patient (5.9%) survived CPR to discharge from the rehabilitation hospital, but he died subsequent to his transfer to the acute hospital. Though the sample size is small, it reflects the total population of patients eligible for CPR who suffered a cardiac arrest. We conclude that CPR is generally not successful in the elderly inpatient rehabilitation population. The growing clinical complexity of the rehabilitation patient demands that health-care providers and their patients more regularly address decision-making issues pertinent to CPR. PMID- 1642824 TI - Use of a polyethylene body jacket to prevent feeding tube removal in an agitated patient with anoxic encephalopathy. AB - Maintaining a feeding tube in place in the agitated patient following a traumatic brain injury or anoxic encephalopathy is a familiar problem. However, a survey of the literature employing the MEDLINE system provided no solutions. This case study of a 36-yr-old patient with anoxic encephalopathy illustrates a new method of preventing feeding tube removal using a modified polyethylene body jacket. The patient had repeatedly pulled out his gastrostomy tube despite the use of four way restraints, a posey, behavior modification and anti-psychotic medications at levels near sedation. A polyethylene jacket with an S-shaped tunnel for feeding tube exit was constructed to cover the abdomen. FINDINGS: 1) The patient was unable to disturb the feeding tube. 2) The recessed design of the jacket's tunnel did not traumatize the feeding tube or obstruct fluid flow. 3) Nursing staff encountered no problems in placing or removing the orthosis. 4) Skin integrity was maintained. 5) The orthosis did not interfere with therapies. PMID- 1642825 TI - Methylphenidate in stroke patients with depression. AB - The treatment of depression after stroke is a difficult clinical problem. Many of the medications used to treat patients with depression in the general population have significant potential side effects that are of particular concern in elderly patients. We reviewed the records of ten patients with stroke treated with methylphenidate for depression during an inpatient rehabilitation program. Improvement was noted in seven patients. This suggests that methylphenidate in the treatment of post-stroke depression merits further study. PMID- 1642826 TI - Liver transplant rehabilitation. PMID- 1642827 TI - Nasal and oral airflow resistors. Site, function, and assessment. AB - Major respiratory resistors situated at the nasal and oral portals are described, and the part they play in disrupting laminar flow of inspiratory air and facilitating the mucosal contact and mixing essential for effective cleansing, warming, and humidification is discussed. The resistors also determine the distribution of oronasal airflow. The contribution of structural and mucovascular elements to nasal airflow resistance is examined and the place of history, rhinoscopy, and rhinomanometry in clinical assessment of nasal patency and its variation in health and with age, race, and disease, is discussed. PMID- 1642828 TI - Serous otitis media. An opportunity for early recognition of nasopharyngeal carcinoma. AB - In a prospective study of 271 new patients with nasopharyngeal carcinoma, 36 (13.3%) were found to have cranial nerve involvement. Serous otitis media (SOM) was found in 98 (41.4%) of 237 patients who had undergone complete otologic assessment. The local control of tumor and actuarial survival of three subgroups of patients, namely, 80 patients with SOM only, 11 patients with cranial nerve palsy only, and 18 patients with both SOM and cranial nerve palsy, were analyzed. The local control of tumor was better in patients with SOM alone than in those with cranial nerve palsy alone; those patients with both SOM and cranial nerve involvement had worse local control as well as survival. As SOM is not uncommon in the diagnosis of nasopharyngeal carcinoma, and adult-onset SOM is otherwise distinctly uncommon, this provides a good opportunity for early recognition and, perhaps, better control of nasopharyngeal carcinoma. PMID- 1642829 TI - Primary squamous cell carcinoma of the parotid gland. AB - We reviewed all cases of possible primary squamous cell carcinoma of the parotid gland treated at Mayo Clinic, Rochester, Minn, from 1960 through 1988. Eighteen cases of primary squamous cell carcinoma of the parotid gland were identified. We report the clinical behavior and results of treatment of these rare parotid gland neoplasms. The age at diagnosis ranged from 48 to 86 years; the majority of patients were aged 65 years or older. Half of the patients presented with an asymptomatic parotid gland mass; a painful mass occurred in 33% of patients. Facial paralysis was noted in 17%, and a neck was the presenting symptom in 11% of patients. All patients underwent parotidectomy, and all or part of the facial nerve was sacrificed in 66% of patients. A neck dissection was performed in 12 patients, five of whom had pathologic confirmation of neck metastasis. Adjunctive radiation therapy was performed in 55% of patients. The overall survival at 5 years was 50%. Deep fixation and facial nerve paralysis were associated with a poor prognosis. Most recurrences developed within 1 year of initial treatment. Regional recurrence was always associated with a rapid death. Our data suggest that aggressive treatment and early detection may result in a better prognosis than is commonly associated with these tumors. PMID- 1642830 TI - The lack of utility of a tumor marker panel in head and neck carcinoma. Squamous cell carcinoma antigen, carcinoembryonic antigen, lipid-associated sialic acid, and CA-125. AB - An ideal tumor marker should be sensitive in tumor-bearing patients while having adequate specificity so that controls do not demonstrate the marker. To date, a single circulating marker has not been identified for squamous cell carcinoma of the head and neck. This study evaluates a panel including squamous cell carcinoma radioimmunoassay, lipid-associated sialic acid, carcinoembryonic antigen, and CA 125. In this population of patients with cancer, serum samples from 101 patients and 88 controls were evaluated. The squamous cell carcinoma radioimmunoassay was the most sensitive marker identified (47.5%), while carcinoembryonic antigen level was elevated in 40.6%, lipid-associated sialic acid level in only 16.8%, and CA-125 level in 7.9%. False-positive results were found with all markers, including squamous cell carcinoma radioimmunoassay (18.2%), carcinoembryonic antigen (18.2%), lipid-associated sialic acid (10.2%), and CA-125 (15.9%). Various combinations of markers did not significantly improve either specificity or sensitivity. Available tumor markers are inadequate for diagnostic purposes in patients with squamous cell carcinoma of the head and neck. PMID- 1642831 TI - Simultaneous chemoradiation in the treatment of advanced head and neck cancer. AB - Fifty-eight patients with either advanced or unresectable squamous cell carcinoma of the head and neck were randomly selected to receive either twice daily radiation alone or twice daily radiation plus concomitant chemotherapy with cisplatin and fluorouracil (5-fluorouracil). There was no advantage in survival or time to progression with the addition of chemotherapy to twice daily radiation for patients with advanced resectable cancers. In the group of patients with unresectable cancers, however, there was a statistically significant advantage to the addition of chemotherapy, both in terms of disease-free survival and date to progression. PMID- 1642832 TI - Defining and predicting tracheoesophageal puncture success. AB - There is considerable variability in the reported success rates of tracheoesophageal puncture due, in part, to the lack of a clear definition of success and a paucity of knowledge about factors that determine success. In this article, we define success on a continuum with the use of a 15-point rating scale that incorporates aspects of use and quality of speech and ability to care for the fistula and prosthesis. We suggest a cutoff score for functional and nonfunctional speakers. We define immediate and short- and long-term success. Variables related to the patient, clinician, surgical procedure, and extent of disease were subjected to a multiple regression analysis to determine which predicted success. Overall success was predicted by greater clinician expertise, younger patient age, and better patient health. We discuss the use of the rating scale and an equation to predict success. PMID- 1642833 TI - Tinnitus and vertigo in patients with temporomandibular disorder. AB - The association of tinnitus and vertigo with temporomandibular disorder (TMD) has been debated for many years. The observation that patients with TMD have otologic symptoms is confounded because tinnitus and vertigo are common symptoms in the normal population. The present study was conducted to determine if tinnitus and vertigo are actually more prevalent in patients with TMD than in appropriate age matched controls. One control group was recruited from patients seeking care for health maintenance and the other from patients seeking routine dental care. We surveyed 1032 patients: 338 had TMD and 694 served as two age-matched control groups. Tinnitus and vertigo symptoms were significantly more prevalent in the TMD group than in either of the control groups. The mechanism of the association of TMD and otologic symptoms is unknown. PMID- 1642834 TI - Extensive defects of the sino-orbital region. Results with microvascular reconstruction. AB - We performed microvascular free-tissue reconstruction of extensive defects in the sino-orbital region in 11 patients. Reconstructions were immediate in 10 patients and delayed in one patient. There was loss of orbit in eight patients, maxilla in eight patients, cranial base in two patients, and skin and soft tissue of the face in six patients. Nine rectus abdominis flaps, one radial forearm flap, and one lateral arm flap were used. Palatal reconstruction with autologous tissue was successful in all patients. Cranial base repairs healed without sequelae or evidence of meningitis. Cosmetically, soft-tissue repair of facial skin was only satisfactory. For large defects, it was difficult to reconstruct the palate and facial soft tissue and to maintain nasal airway patency with a single microvascular procedure. Free-tissue transfers remain the safest and most versatile reconstructive procedure for massive sino-orbital defects after ablation of a tumor. PMID- 1642835 TI - Aesthetic reconstruction of the platyrrhine nose. AB - The platyrrhine nose is characterized by a hypoplastic nonprojected nasal tip, wide flaring alae, underdeveloped premaxilla, and lack of nasal dorsal support. Aesthetic nasal reconstruction is performed utilizing the external rhinoplasty technique. Precise placement of nasal augmentation grafts is facilitated by this technique. The harvesting and utilization of a large autogenous nasal fibrofatty graft for finesse dorsal contouring is described. Seventy-five patients underwent aesthetic reconstruction of the platyrrhine nose. Follow-up ranged from 2 to 7 years. No major complications, including extrusion or significant resorption of augmentation grafts, have been observed. Minor complications included notching of the transverse columella incision in 5% (4/75) of cases, observable suture tract marks along the alar closure incision in 4% (3/75) of cases, and alar incision granuloma in 1% (1/75). A modification of our technique, utilizing a two-layer tension-free closure of the columella and alar incisions, has alleviated these complications. PMID- 1642836 TI - Topical ciprofloxacin vs intramuscular gentamicin for chronic otitis media. AB - Clinical and bacteriological efficacy of topical ciprofloxacin hydrochloride was compared with that of intramuscular gentamicin sulfate in two groups composed of 30 patients each, all of whom were affected by chronic otitis media in the acute stage. Antibiotics were randomly given for 5 to 10 days according to the following schedules: ciprofloxacin hydrochloride, four drops (250 mg/mL in saline solution) administered locally twice a day, or gentamicin sulfate, 80 mg administered intramuscularly twice a day. We admitted to the study only adult patients affected by chronic otitis media in the acute stage with perforation of the tympanic membrane, without cholesteatoma, whose bacteriological culture was positive for Pseudomonas susceptible in vitro to ciprofloxacin and gentamicin. The clinical and bacteriological response was stated 12 hours after the interruption of the treatment, and 2 and 3 weeks later (follow-up). A favorable clinical result was observed in 26 (87%) of 30 patients under ciprofloxacin treatment; in 30 patients receiving gentamicin, a favorable clinical response was observed in 20 (66%) and bacteriological eradication in 13 (43%). No relapse at the follow-up was observed. Topical ciprofloxacin seems to be more effective than intramuscular gentamicin in curing Pseudomonas-caused chronic otitis media in the acute stage. PMID- 1642837 TI - Severe orbital infection as a complication of orbital fracture. AB - Orbital fractures secondary to blunt trauma, and their complications, have been the subject of numerous reports, with little mention of an association with severe orbital infection. Conversely, studies of severe (postseptal) orbital infections rarely make reference to orbital fractures as being a significant pathogenetic factor. In a retrospective study of 130 orbital infections, three cases of severe orbital infection were identified as being associated with an orbital fracture, and are thus presented. In the literature, only anecdotal reports and inconclusive studies address this problem, and its possible prevention. The consequences of a pathologic communication between the paranasal sinuses and the orbit secondary to blunt facial trauma are discussed, along with recommendations for prophylactic management. PMID- 1642838 TI - Mycosis fungoides of the larynx. Report of two cases and review of the literature. AB - Involvement of the larynx by mycosis fungoides is extremely rare with only three reported clinical cases in the English-language literature. We present two patients with laryngeal mycosis fungoides, one of whom presented with vocal cord paresis (progressing to paralysis) as the initial clinical manifestation of laryngeal involvement. Our clinical findings and the observations from the three previous case reports suggest that laryngeal mycosis fungoides has a predilection for the arytenoids, aryepiglottic folds, and the laryngeal surface of the epiglottis. Laryngeal involvement, like other forms of visceral dissemination, appears to manifest clinically in the terminal stages of the disease. The natural history, clinical features, histopathology, and treatment of mycosis fungoides are reviewed and the etiopathology of the vocal cord paralysis is described. PMID- 1642839 TI - Ameloblastoma of the mandible with intracranial metastasis. A case study. AB - Ameloblastoma is an aggressive locally recurring neoplasm of odontogenic epithelium. We describe a case of a mandibular ameloblastoma with a 17-year history of local recurrences followed by two metachronous intracranial metastases. Central nervous system metastasis without pulmonary involvement is previously unreported in a living patient with ameloblastoma. The behavior of this tumor qualifies it as a malignant ameloblastoma. PMID- 1642840 TI - Pulmonary artery sling associated with tracheobronchial malformations. AB - We describe three cases of pulmonary artery slings associated with tracheal stenoses by complete cartilaginous rings and abnormalities in the tracheobronchial branching pattern. This association implicates special problems of management that are different from the simple pulmonary artery sling. Pathologic anatomy, symptoms, diagnostic procedures, and the problems of therapy are described. Considering similar cases in the literature, we conclude that thorough diagnostic evaluation of the tracheobronchial and the cardial system should be carried out in all cases of pulmonary artery sling. Simple correction of the aberrant vessel without correcting the tracheal stenosis is of no value in these cases. In some milder cases, a conservative approach is possible and probably less harmful than an operation. PMID- 1642841 TI - Management of tracheocutaneous fistula. AB - Management of large tracheocutaneous fistulas is not well described in the otolaryngology literature. Some authors have focused on the excision of the fistula tract with or without the use of a strap muscle or sternocleidomastoid flap. Others have proposed staged closures over a period of months to allow secondary healing to occur in order to avoid complications of dehiscence, pneumomediastinum, and infection. We describe a simple technique that utilizes the fistula tract to facilitate closure of a large tracheocutaneous fistula. By using this technique, the surgeon avoids the complications generally associated with the closure of such defects and also the morbidity of waiting for secondary closure to occur. PMID- 1642842 TI - Continuous positive airway pressure. Use in bilateral vocal cord paralysis. AB - Continuous positive airway pressure has been used in the management of a number of upper airway problems, and has become well established as a treatment option for obstructive sleep apnea. The therapeutic value is achieved by an internal splinting effect on the compromised airway. Airway compromise from bilateral recurrent laryngeal nerve trauma can occur with surgical procedures associated with extensive dissection of these nerves. The use of continuous positive airway pressure for the management of bilateral vocal cord paralysis, although not previously described, to my knowledge, is outlined in this article. PMID- 1642843 TI - Pathologic quiz case 2. Laryngeal tuberculosis. PMID- 1642844 TI - Lysozyme localization in normal and diseased human gastric and colonic mucosa. A correlative histochemical, immunohistochemical and immunoelectron microscopic investigation. AB - The distribution of lysozyme in normal and pathological human gastric and colonic mucosa was studied by light and electron microscopic immunocytochemical techniques and compared with histological and histochemical features. Lysozyme was localized in pyloric glandular epithelial cells, mucous neck cells of fundic glands, Paneth cells and some crypt cells of the mature colonic mucosa. In addition, lysozyme was detected in a large spectrum of "immature" or "regenerative" epithelium: neck cells of the gastric regenerative zone, undifferentiated columnar cells of surface and hyperplastic interfoveolar crests of the stomach, regenerative cells in a healed gastric ulcer, some goblet cells in incomplete intestinal metaplasia, cells of the regenerative zone at the bottom of colonic crypts and, finally, fetal intestinal epithelium. Electron microscopically, we localized lysozyme in the central core of mucous granules in the pyloric gastric glandular epithelium and in the dense mucous granules in gastric mucous neck cells. Lysozyme was also detected in some immature mucin producing cells of the gastric regenerative zone and in the rough endoplasmic reticulum of surface hyperplastic columnar gastric cells. At the electron microscopic level, a peculiar correlation between the immunopattern of lysozyme and the morphology of mucous granules has been postulated. All our data support and extend the view that the presence of lysozyme may be related to cell immaturity as well as to a regenerative state of the cell. Finally, the lysozyme distribution and its relation to mucosubstances in gastric and colonic carcinoma suggest that lysozyme should not be considered an exclusive marker of cells of gastric derivation. PMID- 1642845 TI - Disseminated histoplasmosis in a badger (Meles meles) in Denmark. AB - We report the first case of disseminated histoplasmosis in an animal in Scandinavia. Yeast cells compatible with those of Histoplasma capsulatum var. capsulatum were found in the skin, liver, spleen, a kidney, and a lymph node of a wild badger (Meles meles). The diagnosis was confirmed by electron microscopy and immunofluorescence staining of the yeast cells in tissue sections. PMID- 1642846 TI - The redistribution of lymphocytes during adrenaline infusion. An in vivo study with radiolabelled cells. AB - Adrenergic activation is known to occur in sepsis and after major surgery or trauma. An elevated serum concentration of adrenaline is followed by lymphocytosis in peripheral blood even in splenectomized patients. The purpose of the present study was to clarify the redistribution of lymphocytes in the tissues during adrenaline infusion. Lymphocytes were isolated from 24 rabbits, labelled with indium-111-tropolone and reinjected into the rabbits. The next day the rabbits were anaesthetized. Eight rabbits received 3 micrograms of adrenaline i.v. followed by 0.2 micrograms/min, eight received 300 micrograms of adrenaline i.v. followed by 20 micrograms/min, while eight received a saline infusion and served as a control group. The activity of labelled cells was imaged with a gamma camera and computer before, during and after adrenaline infusion. The activity of the spleen decreased to 90% and 94% of initial values during low and high doses of adrenaline. The activity of the bone marrow decreased to 91% and 96%, respectively, while the activity of the heart/lung and the liver increased to 107% and 106% with the high dose of adrenaline. In peripheral blood the lymphocytes increased 10%. It is concluded that lymphocytes are redistributed from spleen and bone marrow to peripheral blood, lungs and liver during adrenaline infusion in this animal model. PMID- 1642847 TI - Aspergillus fumigatus fungaemia and myocarditis in a patient with acquired immunodeficiency syndrome. AB - Necrotizing myocarditis due to Aspergillus fumigatus was a contributory cause of death in a patient with acquired immunodeficiency syndrome and non-Hodgkin lymphoblastic malignant lymphoma of the Burkitt type. A transient remission of the lymphoma had been obtained by cytostatic treatment. A. fumigatus was isolated from blood two weeks before death, but myocarditis was not diagnosed until autopsy. PMID- 1642848 TI - Detection of mycobacteria from blood and bone marrow: a decade of experience. AB - This study reports our experience with methods used at our department from 1981 through 1990 for detection of mycobacteria in blood and bone marrow specimens. Direct inoculation on Lowenstein Jensen media was replaced by Isolator lysis centrifugation followed by inoculation on conventional solid media, and the Bactec 12B and Bactec 13A systems. A total of 3033 specimens were analyzed. A total of 137 mycobacterial isolates were obtained from 42 patients, all HIV positive except one. Mycobacteremia caused by M. avium-intracellulare (83%), M. tuberculosis, M. scrofulaceum and M. kansasii was found. Of 680 blood specimens tested by the last three methods, 7.6% were found to be positive by at least one method and revealed recovery rates of 6.8% for the Isolator-solid media system, 3.4% for the Isolator-12B system and 6.9% for the 13A system (all isolates MOTT). Mean detection times for 21 cultures found positive by all three methods were 23.6, 23.3 and 17.7 days for the Isolator-solid media, Isolator-12B and 13A systems, respectively, with a significantly shorter detection time for the 13A system. Low degree (less than 1 cfu/ml) mycobacteremia (MOTT) caused delay in the Isolator-solid media and the 13A systems and no detection in the Isolator-12B system. Antituberculous therapy significantly prolonged the detection times for MOTT in the 13A system in contrast to the other systems. PMID- 1642849 TI - Evaluation of a Salmonella-specific DNA probe by colony hybridization using non isotopic and isotopic labeling. AB - A 2.3 kilobase (kb) Salmonella probe, JEO402-1, and two subfragments, F1214 (1.3 kb) and F1217 (0.8 kb), have been evaluated by colony hybridization using pure cultures of Salmonella serovars and non-salmonella bacteria. JEO402-1, and its subfragments, F1214 and F1217, hybridized to all of 156 different Salmonella serovars tested, while there was no reaction to 112 non-salmonella strains belonging to 19 genera and 37 species of Enterobacteriaceae. Together with previously published results, the JEO402-1 probe has now been shown to detect a total of 396 Salmonella strains belonging to 214 serovars of Salmonella subspecies I-VI. A total of 178 non-salmonella strains representing 23 genera and 51 species of Enterobacteriaceae have all tested negative with JEO402-1. The hybridization results obtained using a digoxigenin-labeled probe were similar to those obtained with 35S isotopic labeling when complete colony lysis was ensured. PMID- 1642850 TI - Tetracycline resistance genes in Kenyan hospital isolates of Salmonella typhimurium. AB - All 97 strains of Salmonella typhimurium isolated from patients at a hospital in Nairobi, Kenya, during 1988-90 were resistant to tetracycline. The minimum inhibitory concentration (MIC) showed a large distribution range from 1 microgram/ml to 128 micrograms/ml. The strains were heterogeneous with respect to plasmid content, but initially all strains possessed, in addition to other plasmids, a large 60-, 63- or 65-MDa plasmid. The tetracycline resistance genes were characterized using oligonucleotide probes, and 20% of the resistant strains possessed tetracycline type A (tetr A), 6% tetr B, and 4% tetrC genes. Three strains possessed both type A and B tetracycline resistance determinants, which were shown to be located on the large 65-MDa plasmid. There was no correlation between strains isolated from stools, blood, cerebrospinal or epidural fluids, pus, or urine, with respect to the tetracycline genotypes, MIC values or plasmid content. PMID- 1642851 TI - Utility of an internal control for the polymerase chain reaction. Application to detection of Mycoplasma pneumoniae in clinical specimens. AB - The polymerase chain reaction (PCR) was used to amplify a 209 base-pair fragment of Mycoplasma pneumoniae DNA. The amplicon was transferred into a plasmid and a 680 base-pair piece of foreign DNA was inserted between the two amplimer sites. Plasmid DNA was added to the reaction mixture as an internal control for the polymerase chain reaction. Since the original hybridization target sites were included in this construction, one pair of amplimers could be used to amplify both the target DNA and the internal control DNA. Separation of internal control from target DNA after amplification was easily obtained on agarose gel electrophoresis. For the analysis of clinical samples with the polymerase chain reaction, the addition of internal control DNA allowed monitoring of the overall effectiveness of the amplification in each tube. With this technique approximately one-third of the tests were shown to be unsatisfactory due to technical errors or contaminating inhibitors. Adequate internal controls are necessary to avoid false-negative results with the polymerase chain reaction. PMID- 1642852 TI - DNA content in primary tumours and lymph node metastases in colorectal adenocarcinoma. AB - In 18 consecutive patients operated on for colorectal carcinoma of Dukes' stage C, the DNA patterns were determined in multiple samples of the primary tumours and in all detected lymph node metastases. Single-cell microspectrophotometry on Feulgen-stained smears of fine-needle aspirates was used. When the most aggressive DNA pattern was considered representative, 12 primary tumours (67%) were designated as aneuploid. The frequency of aneuploidy among the metastases was almost the same (63%). In 15 cases (83%) the DNA patterns displayed by the metastatic lymph nodes were also found in the corresponding primary tumour, while in the remaining three cases (17%) the DNA pattern in the lymph node metastases was not seen in any of the multiple samples from the primary tumour. The observed tumour DNA heterogeneity may reflect either the multicellular origin of the tumour cells or the continuous evolution and progression of a neoplasm of unicellular origin, and may partly explain the dissimilarities between the DNA patterns of the primary tumour and the lymph node metastases. Biopsy samples from a number of metastatic lymph nodes are therefore required to ensure representativeness and to permit an adequate analysis of the prognostic role of the DNA ploidy status in lymph node metastases from colorectal cancer. PMID- 1642853 TI - Detection of Chlamydia trachomatis antigens in first-void urine to identify asymptomatic male carriers. AB - Early morning first-void urine collected from 279 sexually active Swedish male recruits (mean age 19.5 years) was tested by two commercial enzyme immunoassay (EIA) kits, MicroTrak and IDEIA III, and by MicroTrak direct fluorescence assay (DFA), to detect Chlamydia trachomatis antigens. A result was assumed to be true positive when any of the two non-culture tests were positive for the same specimen. In one case where only DFA was positive, confirmatory chlamydial testing was performed by isolating the organism from a urethral swab. On these premises, the number of true-positive men was 26 (9.3% of all men studied). The sensitivity, specificity, positive predictive value and negative predictive value for MicroTrak EIA were 85%, 98%, 85%, and 98%, respectively. IDEIA III was less sensitive than MicroTrak EIA (42% vs 85%). In conclusion, the diagnosis of asymptomatic chlamydial infections in men can be established with reasonable accuracy by the detection of Chlamydia antigens in urine samples using MicroTrak EIA. PMID- 1642854 TI - Detection and identification of Mobiluncus species by direct filter hybridization with an oligonucleotide probe complementary to rRNA. AB - A hybridization assay for direct detection and identification of Mobiluncus species has been developed and tested. A [32P]-labelled synthetic oligonucleotide probe, complementary to a nucleotide sequence in the variable region V8 of Mobiluncus 16S ribosomal RNA, was utilized. One of the advantages of using rRNA as target molecule for the hybridization assays is the copy number of rRNA, which can be as high as 10(4), and that additionally three to six sites on the minus strand of the DNA gene can be utilized. This probe was found to be sensitive and to react with 62 of 68 tested typical or atypical Mobiluncus isolates. It was also specific, and was shown not to react with 96 tested unrelated bacterial species and isolates, including taxonomically closely related species like Actinomyces or Bifidobacterium spp., or with bacteria isolated from the vagina of both healthy persons with an undisturbed flora, as well as from patients suffering from the bacterial vaginosis syndrome (BV). PMID- 1642855 TI - Susceptibility of strains of the Mycobacterium tuberculosis complex to fusidic acid. AB - The activity of fusidic acid was studied in 40 strains of M. tuberculosis (of which 20 strains were mono- or multiresistant to standard antituberculosis drugs) and 10 strains of M. bovis. Minimum inhibitory concentration (MIC) was determined by the radiometric (BACTEC) broth method. The MIC for the 50 strains varied between 8 and 32 mg/l, with a MIC90 of 16 mg/l for M. tuberculosis and a MIC90 of 32 mg/l for M. bovis. Minimal bactericidal concentration (MBC, defined as the lowest concentration of fusidic acid which killed 99% or more of the population) varied between 32 mg/l and 500 mg/l, with a MBC90 of 250 mg/l for M. tuberculosis and 500 mg/l for M. bovis. No cross-resistance to other antituberculosis drugs (ethambutol, isoniazid, rifampicin, streptomycin, pyrazinamide, ofloxacin, ciprofloxacin) was observed as strains resistant to one or more standard antituberculosis drugs were as susceptible to fusidin as sensitive strains of M. tuberculosis. No synergism or antagonism could be demonstrated when fusidic acid was combined with either ethambutol, isoniazid, rifampicin or streptomycin against strains of M. tuberculosis resistant to one or more standard antituberculosis drugs. Addition of pooled human serum to the medium increased both MIC and MBC by factors of 4 and 8 at serum concentrations of 10% and 50%, respectively. Single-step mutation to high-level resistance to fusidic acid at a frequency of less than 1.7 x 10(-8) could be readily selected at four times the MIC. These fusidic acid-resistant organisms had a generation time 2.0-2.7 x longer than their parent organisms. PMID- 1642856 TI - Information processing in the separated hemispheres of callosotomy patients: does the analytic-holistic dichotomy hold? AB - The characterization of the left and right cerebral hemispheres as analytic and holistic, respectively, was evaluated with callosotomy patients. This distinction was operationalized by reference to the work of Garner, Kemler Nelson, and their colleagues on separable (analytic) and integral (holistic) dimensions of cognition. In one experiment, patients were asked to make similarity judgments when faced with triads of stimuli such that one pair matched on a criterial attribute (analytic) and another pair showed a family resemblance (holistic). The right hemisphere showed a stronger bias to judge on the basis of the criterial attribute. In a second experiment, each hemisphere was engaged separately in a concept formation task. Depending on the exemplars in a particular set, analytic or holistic processing was seen in either hemisphere. However, the left hemisphere was more likely to engage in analytic processing. The results suggest that both hemispheres are capable of either type of processing and may use either mode, depending on the nature of the task and stimulus material. Thus, the analytic/holistic distinction may not provide a simple, generalizable description of information processing differences between the two hemispheres. PMID- 1642857 TI - Clarification of the dual task dilemma: lateralized effects for perfunctory and purposeful tasks in left- and right-handed males. AB - The hypothesis that behavioral asymmetries with the dual task paradigm represent manual dominance was investigated with right- and left-handed males performing verbal and spatial tasks ordered by complexity. Lateralization was assessed for nonideational (perfunctory) and ideational (purposeful) components of tasks with multivariate and ANCOVA procedures. The outcomes of prerequisite tests showed the assumptions for conducting ANCOVA procedures were not satisfied with different handedness groups in the same design. However, results of the multivariate analyses suggest lateralized effects are more likely to represent the cognitive task when interference is high and may represent manual dominance when interference is low. PMID- 1642858 TI - Confabulation in Alzheimer's disease. AB - Confabulation is present when memory is disturbed, but does it occur in Alzheimer's disease (AD) where memory abnormalities are often severe? In this study, confabulation was assessed prospectively in 26 AD patients and 15 normal elderly (NE) controls using a neuropsychological battery specifically designed to assess different types of memory errors. The results indicated that the AD group made significantly more verbal intrusions than the NE group. These findings provide evidence for the feasibility of eliciting confabulatory-type behavior during clinical assessment and support previous reports which have documented verbal intrusions as a common accompaniment of the memory impairment manifested by AD patients. PMID- 1642859 TI - Manipulations of subjects' level of arousal in dichotic listening. AB - The effects of manipulation of the subject's level of arousal on the right ear advantage (REA) in dichotic listening to CV-syllables were investigated. There were three different arousal manipulations under high and low incentive levels. Negative manipulations involved threat of electric shock (high incentive) or noise (low incentive) for incorrect answers. Positive manipulations involved the possibility to earn a substantial (high incentive) or small (low incentive) sum of money for correct answers. A third, neutral, condition involved no specific instructions about consequences for correct or incorrect answers. Thirty-six females participated in the study. Heart rate was recorded as an independent measure of change in level of arousal as a function of the experimental instructions. The results showed that the high negative condition abolished the REA effect, with a non-significant difference between ears. This was caused by both an increase in correct left ear reports and a decrease in correct right ear reports. The other arousal conditions had no effect on the REA. The results are discussed in terms of right hemisphere dominance for aversive emotional processing in dichotic listening. PMID- 1642860 TI - Visual field differences in an object decision task. AB - Two experiments are reported which investigate hemispheric processing in an object decision task. Experiment 1 used 40 pictures of objects, and 40 pictures of nonobjects, and subjects decided manually whether each lateralized stimulus represented an object. Results indicated an interaction between visual field and response (yes versus no). There was a right visual field advantage for positive responses, but no difference between visual field for negative responses. Positive responses were faster than negative responses, and this effect was more marked for right visual field presentations. These results were replicated in a second experiment. The results are interpreted as reflecting a left hemisphere superiority at accessing stored structural descriptions of known objects. The possibility that left and right hemispheres use different methods of carrying out the task is also discussed. PMID- 1642861 TI - Mathematics performance in left and right brain-lesioned children and adolescents. AB - Children and adolescents with unilateral left- or right-hemisphere lesions were administered a standardized test of mathematics ability and a battery of experimental tests that examined the components of numerical and arithmetic processing. All lesioned groups showed at least marginally lower scores on the standardized test than the controls. More importantly, lesion-related deficits in performance were observed, especially for younger left-lesioned subjects (ages 7 12), on the verbal counting, digit matching, speeded addition, and written subtraction tasks; deficits among younger right-lesioned subjects were similar in nature, yet less pronounced than in the left-hemisphere group. Older left lesioned subjects showed differences from their controls only on complex verbal counting and speeded addition. Correlations among the various measures indicated two further points. First, earlier onset of left-hemisphere lesion is associated with more serious disruption of mathematical processing. Second, these disruptions are not well assessed by a typical standardized test of mathematical performance, but are clearly in evidence with more precise, focused tasks. PMID- 1642862 TI - Perceptual closure and object identification: electrophysiological responses to incomplete pictures. AB - Event-related potentials were recorded during the naming of pictures of concrete objects. The pictures were presented at three levels of completeness: 10, 30, and 60%. The ERP waveforms were evaluated according to the level of picture completeness and the correctness of naming. A negative wave in the latency range of 250-550 ms was significantly more negative when the pictures were more incomplete, regardless of the correctness of response. This N400 wave is proposed as being related to hypotheses about the identity of the object. A late positive wave in the latency range of 550-650 ms followed the negativity, but only when the response was correct. This may reflect the subject's certainty about the perceptual analysis, a verification of the identity of the object. A slow parietal negativity lasting up to 2 sec was largest for the least complete picture. This therefore varied with the perceptual difficulty. PMID- 1642863 TI - Preoperative ultrasonographic verification of peritonsillar abscesses in patients with severe tonsillitis. AB - Infection around the tonsillar region does not always mean the presence of a peritonsillar abscess although the condition of peritonsillitis without abscess formation may clinically present similarly. It is, however, of therapeutic importance to distinguish between the two conditions. Treatment for abscess is surgical: aspiration, incision and drainage or immediate tonsillectomy. In contrast, phlegmonous peritonsillitis only requires antibiotics. In order to evaluate the diagnostic implications of preoperative ultrasonography in patients referred for treatment of peritonsillar abscess, 27 consecutive patients were subjected to bilateral ultrasound examination to visualize the tonsillar region. The transducer used was placed just below the mandibular angle, pointing posteriorly and cranially. The results of this study showed that it was possible to verify the presence of an abscess in approximately 90% of the cases. We suggest that this examination be performed whenever the normal clinical examination is insufficient due to trismus, lack of patient cooperation, etc. PMID- 1642864 TI - Expression of glycoconjugates in the mouse inner ear after prenatal irradiation. AB - Irradiation of the murine fetal inner ear is known to produce damage both to the vestibular and cochlear parts in the adult mouse. Fluorescein-labelled lectins were used to reveal possible differences in the glycoconjugate content between normal and irradiated inner ears. In the vestibular part, the otoconia showed the highest uptake of labelled sugars. This uptake was weaker after irradiation when compared to non-irradiated specimens. The type I hair cells in the ampulla and in the utricle showed a weaker uptake, but no labelling was demonstrated in the type II hair cells compared to the non-irradiated controls. In the cochlear part of the inner ear almost no uptake of fluorescent-binding lectins could be demonstrated in the irradiated groups except for in the tectorial membrane. In the endolymphatic sac no uptake was shown after prenatal irradiation. These findings are discussed and correlated to the already known damage of the inner ear following prenatal irradiation. PMID- 1642865 TI - DNA-flow cytometry of head and neck carcinoma: the importance of uniform tissue sampling and tumor sites. AB - Flow cytometric DNA ploidy measurements using deparaffinized tumor specimens were performed on 46 squamous cell carcinomas of the head and neck, including 22 carcinomas of the oropharynx, 18 carcinomas of the larynx and six carcinomas of the oral cavity. Aneuploidy was found in 14 of these tumors with carcinomas of the larynx and oral cavity showing almost equal percentages of DNA aneuploidy (10/18 and 3/6, respectively). In contrast, only 1 of the oropharyngeal carcinomas was aneuploid. Accurate microscopy-controlled sampling of tumor tissue from the histological tissue blocks was found to be mandatory in order to obtain reliable ploidy measurements. PMID- 1642866 TI - Value of the supraomohyoid neck dissection with frozen section analysis as a staging procedure in the clinically negative neck in squamous cell carcinoma of the oral cavity. AB - A retrospective analysis was performed to evaluate with the efficacy of elective supraomohyoid neck dissection (SOND) with frozen section (FS) analysis in 57 newly diagnosed patients (62 SONDs) with squamous cell carcinoma of the oral cavity. The protocol included sampling of both the most suspect and largest node in the jugulodigastric region (if present) and the most distal jugulo-omohyoid lymph node (if present). These nodes were then studied with FS histological examination. In the absence of evident nodes for FS analysis during surgery, histological examination uncovered occult metastatic disease in 3 of 11 SOND specimens. Among the remaining patients FS analysis revealed occult metastatic disease in 10 of the 51 samples (19.6%). In these latter cases surgery was continued using standard or modified radical neck dissection en bloc with the primary tumor. In 1 specimen only a single metastasis was found outside the original extent of the SOND. Among 41 FS analysis reports stating the absence of metastatic disease, histological examination of the SOND specimens demonstrated occult nodal disease in 7 (17%). All of the cervical metastases appeared in the ipsilateral side of the neck. False FS reports did not occur. In the histologically proven absence of metastatic disease in the SOND specimens, disease recurrence in the neck occurred only in 3 cases (7%), all in the presence of local failure: once in the previous SOND area, once in the ipsilateral supraclavicular region and once on the contralateral side.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642867 TI - Changes in the electrochemical composition of cochlear fluids after intracisternal application of doxorubicin in the rat. AB - Since doxorubicin (Adriamycin) is known to bind on membranous negative surface charges, its effect on the electrochemical composition of the cochlear fluids was studied in rats. Doxorubicin was infused into the cerebrospinal fluid via the lateral cerebral ventricle. The endocochlear resting potential was recorded, and endolymph and perilymph of the scala vestibuli were collected from the basal cochlear turn before and 1, 2, and 4 h after the drug application. Na+, K+, and Cl- concentrations and osmolality of the endolymph and perilymph were measured in 1 nl aliquots. In perilymph, Cl- concentration increased 4 h after doxorubicin treatment to reach a concentration 8 mM higher than recorded initially. In endolymph, the endocochlear potential decreased by 5 mV/h while its K+ concentration and osmolality increased by about 3 mM/h and 4 mosmol/kg H2O per hour, respectively. These results suggest that the negative surface charges demonstrated on Reissner's membrane may play a role in the homeostasis of endolymph. PMID- 1642868 TI - The relationship between smooth and saccadic components in smooth pursuit. AB - Eye movements in smooth and pathological (saccadic and ataxic) pursuit patterns were separated by the use of the inverse fast Fourier transform. Results showed that the smooth component was significantly smaller while the saccadic component was significantly greater in the pathological pursuit patterns than in the smooth pursuit pattern. In addition, the smooth and saccadic components showed a linear relationship. These findings give some support to the threshold theory in explaining the relationship between smooth pursuit and saccades. PMID- 1642869 TI - Tetramethylammonium for in vivo marking of the cross-sectional area of the scala media in the guinea pig cochlea. AB - A physiologic technique was developed to measure endolymphatic cross-sectional area in vivo using tetramethylammonium (TMA) as a volume marker. The technique was evaluated in guinea pigs as an animal model. In the method, the cochlea was exposed surgically and TMA was injected into endolymph of the second turn at a constant rate by iontophoresis. The concentration of TMA was monitored during and after the injection using ion-selective electrodes. Cross-section estimates derived from the TMA concentration measurements were compared in normal animals and animals in which endolymphatic hydrops had been induced by ablation of the endolymphatic duct and sac 8 weeks earlier. The method demonstrated a mean increase in cross-sectional area of 258% in the hydropic group. Individually measured area values were compared with action potential threshold shifts and the magnitude of the endocochlear potential (EP). Hydropic animals typically showed an increase in threshold to 2 kHz stimuli and a decrease in EP. However, the degree of threshold shift or EP decrease did not correlate well with the degree of hydrops present. PMID- 1642870 TI - Primary cultures of middle ear epithelial cells from chinchillas. AB - A reproducible method is presented for primary cultures of middle ear epithelial cells (MEEC) from chinchillas. The MEEC were first dissociated with protease and grown on collagen-coated membrane using a culture medium containing equal volumes of Dulbecco's modified Eagle medium and Ham's F12 supplemented with 0.5% fetal bovine serum. Outgrowth of cells was first noted within 24 h, reaching confluency in 6-7 days. These cells grew in a monolayer and appeared to be ovoid or polygonal. By immunofluorescence microscopy, these cells stained for cytokeratin, but not for type III collagen. In contrast, fibroblasts stained for type III collagen, but not for cytokeratin. Based on growth characteristics, morphology, and immunofluorescent findings, these cells were determined to be epithelial cells. To retard the outgrowth of fibroblasts, 5 mM putrescine was added to the culture medium on the 2nd day of explant. Contamination with fibroblasts was consistently less than 5% when defined as type III collagen-positive cells. Establishment of a method for the primary culture of MEEC will provide a new approach for studying the role of epithelial cells in the pathogenesis of various types of otitis media. PMID- 1642872 TI - Stapedius reflexes to electrical stimulation in the rabbit for the assessment of hearing. AB - The possibility of using electrically induced stapedius reflexes as a means of objective hearing evaluation was investigated in the rabbit as an animal model. The contralateral stapedius reflex to acoustic and electrical stimulation was measured in anesthetized rabbits. For electrical stimulation, the middle ear was opened surgically and stimulation was applied by a monopolar electrode placed at or into the round window. Contraction of the middle ear muscle was monitored by digital sampling and averaging of the impedance changes in the contralateral ear. Acoustically evoked reflexes were recorded within expected limits despite anesthesia. The level of the electrical stimulus was raised until mass reflexes of the neck muscles were observed. A contralateral stapedius reflex to electrical stimulation could not be demonstrated. In our experiment, monopolar electrical stimulation at the round window could not elicit contralateral stapedius reflexes. PMID- 1642871 TI - Effects of organic acids on stria vascularis ultrastructure and function in the chinchilla. AB - The purpose of this study was to compare the effects of several organic acids (probenecid, sodium salicylate and penicillin G) on the endocochlear potential (EP) and the ultrastructure of the stria vascularis of the chinchilla with the effects of furosemide on these parameters. Chinchillas received 50 mg/kg i.v. doses of probenecid, sodium salicylate or penicillin G, or 25 mg/kg i.v. furosemide. The EP was monitored continuously before and for 60 min afterwards. The stria vascularis was removed at 10-min intervals from animals and from 10 to 60 min after the injection of these agents. Specimens were then processed for transmission electron microscopy. Only furosemide had an effect on the EP, causing a reversible reduction. The reduction of the EP was accompanied by the appearance of edema in the intercellular spaces of the stria vascularis. No significant edema was found after probenecid, sodium salicylate or penicillin G. This was consistent with the finding that none of these latter three agents affected the endocochlear potential. PMID- 1642873 TI - Caloric irregularity in experimentally induced perilymphatic fistula. AB - The term "caloric irregularity" was coined to refer to a gross irregularity in the amplitude and/or frequency of a caloric-induced nystagmus, having a variable slow-phase velocity and prolonged duration. Twelve of 46 guinea pigs with experimentally induced perilymphatic fistula had irregular responses to the ice water caloric test 1 week after creation of a fistula. The long-term vestibular consequences in animals with caloric irregularities were either resolution and return to normal function (i.e. caloric return) or continuing deterioration to canal paresis. Morphological examination of ears with caloric irregularity revealed that there had been partial collapse of the membranous labyrinth and the creation of a floating labyrinth. PMID- 1642874 TI - Management of cervical lymph nodes in patients with head and neck cancer. AB - The status of the cervical lymph nodes is the single most important prognostic factor in head and neck cancer. Unfortunately, clinical assessment of the neck is not very accurate, although newer imaging techniques such as CT, MRI and ultrasound-guided fine needle aspiration cytology can be used to improve upon the results of clinical palpation alone. While diagnostic techniques remain less than 100% accurate, the risk of occult disease in the neck will remain. If this occurrence is judged to be greater than 15-20%, elective treatment to the neck may then be justified. When the neck is treated surgically, histological information can be gained which has both prognostic and therapeutic implications. Indications for the use of surgery and radiotherapy for the elective and therapeutic management of the neck and the results of such treatment are discussed. PMID- 1642875 TI - Pitfalls in the histopathologic diagnosis of pyogenic granuloma. AB - The term pyogenic granuloma (PG) is a misnomer. The histopathologic appearance is fairly characteristic, the lesion being in fact a lobular capillary hemangioma. The recognition of PG as a clinically polypoid or exophytic, circumscribed lesion is of importance to both the clinician and the pathologist, as this feature distinguishes PG from most malignant vascular tumors. Although PG may be multiple, especially on the skin, and necrosis is not uncommon, invasion of adjacent structures is not seen. Diagnostic pitfalls occur histologically when the characteristic lobular configuration of PG is not recognized because of a solid growth pattern of endothelial proliferation, the presence of brisk mitosis, intervascular stromal fibrosis or spindle cell proliferation, and occasionally an epithelioid appearance of endothelial cells. The different vascular neoplasms that may be confused with PG are discussed, and the clinical and histopathologic features of PG are emphasized. PMID- 1642876 TI - Distribution and co-localization of immunoreactive helospectin with vasoactive intestinal polypeptide and peptide histidine methionine in human nasal mucosa, soft palate and larynx. AB - Regulatory peptide immunoreactivities reported in the upper respiratory system of man include vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM), which are co-localized in a network of fine varicose nerve fibers. The present study was undertaken to examine the possible occurrence and distribution of the recently described VIP-like peptide helospectin. Double immunofluorescence labelling showed that helospectin is co-localized with VIP and PHM. In addition to nerve fibers containing all three peptides, scattered nerve fibers were detected that were only immunoreactive to helospectin but not to VIP and/or PHM. The distribution of helospectin/VIP/PHM immunoreactive nerve fibers around blood vessels and in close relationship to seromucous glands indicates their possible involvement in the regulation of blood flow and secretion. PMID- 1642877 TI - Eustachian tube dysfunction in patients with nasopharyngeal carcinoma, pre- and post-irradiation. AB - Eustachian tube function tests were performed in 34 patients with nasopharyngeal carcinoma before and after irradiation. Tubal dysfunction prior to irradiation in these patients was due to functional impairment. However, tubal dysfunction after irradiation was due to both organic obstruction and functional impairment. Organic obstruction of the tube was found to be severe with higher dosages of irradiation (to 80 Gy) resulting in subsequent otitis media. In our experience, higher doses of irradiation should be avoided if possible, but insertion of a ventilation tube should be done if a high dose of irradiation is planned. PMID- 1642878 TI - Magnesium levels in middle ear fluids and sera in otitis media with effusion. AB - Middle ear fluids (MEE) and matched sera (S) were obtained from 50 patients with serous otitis media and magnesium levels were measured to determine if magnesium concentration was distinctly varied in otitis media with effusion (OME). The MEE/S ratio was considerably raised along with transient sensory hearing loss in chronic OME when compared with acute OME. The higher magnesium level found in the MEE implies that it is probably produced locally by the middle ear mucosa and may contribute to the hearing loss found. We also regard the MEE/S ratio as a prognostic factor in OME. PMID- 1642879 TI - A randomized trial of neoadjuvant vs concomitant chemotherapy vs radiotherapy alone in the treatment of stage IV head and neck squamous cell carcinoma. AB - Treatment results of irradiation as a single treatment for advanced stage IV unresectable head and neck cancer remains uniformly poor and apparently has not changed with the most recent improvements in oncological care. Despite several negative results of randomized studies, neoadjuvant or concomitant chemotherapy and radiotherapy seems to improve the number of complete responses and also the duration of disease-free survival. The present study was designed to determine the feasibility, potential risks and benefits of the two methods of combined treatment and radiotherapy alone on the management of advanced unresectable squamous cell carcinoma of the upper respiratory and digestive system. From 1983 to 1986, 90 patients entered the trial. Thirty patients were randomized to each study group: radiotherapy alone (70 Gy); neoadjuvant chemotherapy (vinblastine, mitomycin, cisplatin, and bleomycin) and radiotherapy; concomitant chemotherapy (cisplatin and bleomycin) and radiotherapy. An increased frequency of complete responses (33%) was seen in patients treated with the two different combinations of chemotherapy and irradiation compared to irradiation alone (10%). However, toxicity was more common in patients treated with the two modalities of combined treatment and there were no differences in overall survival rates (P = 0.706). PMID- 1642881 TI - Malignancy of a cystadenolymphoma of the parotid gland. AB - The authors describe malignant degeneration of the epithelial component of a cystadenolymphoma (CAL) of the parotid gland in a 79-year-old man. This development of carcinoma in CAL is a very rare occurrence, with only eight cases described thus far in the literature. PMID- 1642880 TI - Extracellular matrix in the rat spiral limbus. AB - The matrix of the spiral limbus is obviously a special form of the intercellular substance. In the present study, the rat's spiral limbus was investigated by electron microscopy after fixation with ruthenium red and tannic acid and immunofluorescence to demonstrate matrix components. Collagen types I, II, V, VI, VII, IX and XI and fibronectin were not observed. Collagen type II and cartilage specific proteoglycans, however, occurred in large quantities. The basal lamina of interdental cells and inner sulcus cells did not contain any collagen type IV, while the basal lamina of the capillaries had only minor amounts. Laminin and nidogen appeared in large amounts in the basal lamina. After fixation with tannic acid, the matrix between the interdental cells and the capillaries contained 20- to 22-nm-thick single and irregularly running fibrils as well as plaques of a fine granular material. After fixation with ruthenium red, 30- to 60-nm-thick, electron-dense granules occurred and most probably consisted of proteoglycans. These findings indicate that the composition of the matrix of the spiral limbus is similar to that of cartilage but not identical. PMID- 1642882 TI - High-efficiency cDNA cloning: a comparison of electroporation and in vitro packaging. AB - The production of complete cDNA libraries from minimal amounts of starting material (i.e., mRNA) is a major challenge for cDNA cloning technology. This paper reports the cDNA cloning efficiencies of electroporation and in vitro packaging. These two methods produce a tremendous number of recombinant clones (greater than or equal to 1 x 10(8) clones/micrograms cDNA) although electroporation generates more clones at nearly all cDNA concentrations used in a ligation reaction. PMID- 1642883 TI - PCR libraries of ancient DNA using a generalized PCR method. AB - We describe a generalized PCR method that will amplify fragments of DNA without any knowledge of sequence using a single primer. Although we are presently using this method to amplify DNA fragments isolated from ancient preserved tissues, in effect, producing PCR libraries, it may prove to have other applications. PMID- 1642884 TI - Spontaneous hazardous chemical explosion of unopened bottles of diethyl pyrocarbonate (DEPC). PMID- 1642885 TI - Colony-hybridization apparatus with batch-processing capacity. PMID- 1642886 TI - Purification of BrdUrd-substituted DNA by immunoaffinity chromatography with anti BrdUrd antibodies. PMID- 1642887 TI - Effect of dimethyl sulfoxide concentration on specificity of primer matching in PCR. PMID- 1642888 TI - Use of petroleum jelly for sealing coverslips in crystallization trials. PMID- 1642889 TI - A simple and rapid method for the preparation of phage DNA suitable for Southern analysis. PMID- 1642890 TI - Detection of DNA in Southern blots by chemiluminescence is a sensitive and rapid technique. PMID- 1642891 TI - Random primer labeling of DNA in high melting point agarose gel slices for chemiluminescent detection. PMID- 1642892 TI - Subtractive immunization techniques for the production of monoclonal antibodies to rare antigens. AB - Traditional techniques for the production of monoclonal antibodies usually result in generation of monoclonal antibodies to immunodominant molecules. To enhance the production of monoclonal antibodies to rare or less immunodominant antigens, subtractive immunization techniques have been employed. This study compared the ability of several subtractive immunization techniques to suppress the immune system to a given antigen. Neonatal tolerization, chemical immunosuppression with cyclophosphamide, a combination of the two and various permutations of these techniques were compared. The results from this study indicated that chemical immunosuppression with cyclophosphamide was the most effective subtractive immunization technique and that the cyclophosphamide regime employed was a critical determinant in the success of chemical immunosuppression. PMID- 1642893 TI - Serum-free, defined medium for the growth and differentiation of murine erythroleukemia cells. AB - Murine erythroleukemia (MEL) cells are frequently employed to study both cell growth and erythroid differentiation. Although these cells are easily cultured and induced to differentiate, they are routinely maintained in a medium that contains 10%-15% fetal bovine serum. Because of the variability between different lots and the cost of serum, it was desirable to define a serum-free medium in which to culture MEL cells. In the present work, a totally serum-free, defined medium is described that supports both normal cell growth and dimethyl sulfoxide induced differentiation in the two MEL cell lines examined (DS-19 and 270). A variety of hormones and biological compounds are examined in this medium to determine their effects on growth and differentiation. This medium does not support the growth of the mouse hepatoma cell line. PMID- 1642894 TI - Expression of a heterodimeric Fab antibody protein in one cloning step. AB - A new method is presented for creating antibody expression libraries in Escherichia coli. Rather than perform two cloning steps to express the heavy and light chains of the antigen binding domain, we have used a fusion-PCR method to link the coding regions for heavy and light chain sequences in a single DNA molecule prior to vector ligation. This greatly simplifies the construction of antibody expression clones. PMID- 1642895 TI - CHELATOR: an improved method for computing metal ion concentrations in physiological solutions. AB - An algorithm is presented for the calculation of metal ion concentrations from given total metal concentrations (and vice versa) in physiological media containing metal-chelating compounds. In such media, conditions differ from those used for stability constant determination of metal-chelator equilibria; therefore calculated metal ion concentrations are incorrect. We recompute stability constants to reflect the effects of ionic strength and temperature of physiological solutions. Twelve different equilibria can be considered per metal chelator pair. The computer program also calculates the contribution of ionized species of metals, chelator, complexes and pH buffers to ionic strength. Measurements with a Ca-selective electrode and with fura-2 show that calculated ionic Ca2+ concentrations are correct from 10 nM up to the millimolar range. The importance of the correct calculation of metal ion concentrations in physiological experiments is demonstrated by data, and derived kinetic parameters, on Na+/Ca2+ exchange and the ATP-dependent Ca2+ pump of enterocyte plasma membrane vesicles. The program is written in Turbo Pascal and will run on IBM-compatible computers. It is menu-driven and supports the use of a Microsoft mouse. PMID- 1642896 TI - A BASIC computer program for analyzing endpoint assays. AB - We present a computer program that is based on Karber's approximation of endpoint titers, written in GW-BASIC and provides an easy means for analyzing the results of dilution endpoint assays. The program provides estimates of standard error that are not possible from other statistical procedures for this type of data. PMID- 1642897 TI - Convenient methods for the display, comparison and interpretation of amino acid composition data. PMID- 1642898 TI - A graphical user interface for quantitative imaging and analysis of electrophoretic gels and autoradiograms. AB - DNA/GUI (DNA Graphical User Interface) is an interactive software system for rapid and efficient analysis of images of the types used in genome mapping, such as autoradiograms and electrophoretic gels. Images are digitized using a commercially available charge-coupled-device (CCD) camera system and analyzed on a graphics workstation using a menu-driven user interface. DNA/GUI features automatic lane and band detection, simultaneous display of multiple images and a unique spatial-normalization algorithm. Images and their associated data are archived and easily available for later recall. Preliminary results indicate that DNA/GUI is a useful tool in the analysis and comparison of images used in a variety of applications such as genetic-linkage analysis and DNA restriction mapping. The interactive display software is based on the X Window System and is therefore readily portable to a variety of graphics workstations. PMID- 1642899 TI - High sensitivity quantification of RNA from gels and autoradiograms with affordable optical scanning. AB - To increase sensitivity and to improve normalization of RNA levels in Northern blot analysis, a comparatively inexpensive optical scanner was utilized for digitizing photonegatives of ethidium bromide stained gels and autoradiograms. The optical scanner captures the image with a maximum resolution of 300 dots per inch by assigning one of 256 gray levels (8-bit) to each dot in the image. With the use of the public domain NIH Image program (requires a Macintosh II and an 8 bit video card), gel or autoradiogram bands in the digitized image are selected and their average gray scale density measured. We found that the digitized image of a photonegative of a TAE (Tris-acetate/EDTA) agarose gel, loaded incrementally with 50-1500 ng total RNA, produced a linear response over a 4-fold range down to 100 ng (R2 greater than 0.950). In utilizing "quantification" gels like this, RNA samples that are too dilute or too small for traditional spectrophotometric techniques can be normalized and loaded uniformly onto subsequent Northern gels. Results from autoradiogram scans demonstrate highly linear gray scale responses over a 4-fold range of total RNA (R2 greater than 0.950) that are reproducible with different blots and probe types (e.g., riboprobe, cDNA and oligonucleotide). In addition, we describe a normalization technique using a 30-mer oligonucleotide probe for rat 28S ribosomal RNA as a measure of total RNA loaded per gel lane. Altogether, this scanning, ribosomal RNA normalization system allows the measurement of relative changes between 20% and 400% using standard autoradiographic methods. PMID- 1642900 TI - The maternal-fetal relationship in human pregnancy: an immunogenetic perspective. AB - Although the mechanisms by which the fetal allograft escapes rejection are still poorly understood, abundant evidence has accumulated suggesting multiple roles for major histocompatibility complex (MHC) genes in pregnancy. Specific maternal MHC genotypes and maternal-fetal histocompatibility have been associated with recurrent spontaneous abortion, decreased fecundity, segregation distortions, altered sex ratios, fetal growth rates, and maternal autoimmune disease progression. In this review, the evidence for a variety of MHC gene effects in human pregnancy is considered. PMID- 1642901 TI - Distribution of GM allotypes and deleted IGHG1 haplotypes in the Sel'kups in comparison to the Forest Nentsi of northwestern Siberia. AB - Northern Sel'kup people residing in the upper Taz and the tributaries of Turukhan Rivers were typed for immunoglobulin heavy chain (GM) allotypes. The Sel'kups exhibited a unique GM*-G haplotype circulating within the tribe in low but almost polymorphic frequency along with common GM*F B and GM*A T haplotypes, the former a Caucasian marker and the latter a northern Oriental population's marker. Contemporary Sel'kups show a higher frequency of GM*A T than the westwardly situated Forest Nentsi, reflecting recent historical events in the region such as admixture with the Evenki of Middle Siberia. Within the area located between lower Ob and Yenisey rivers, the unique GM*-N B haplotype, restricted to the Forest Nentsi, and the unique GM*-N' G haplotype, restricted to the Sel'kups, serve as GM markers discriminating between these two adjacent tribes. PMID- 1642902 TI - Genetic polymorphism of IgG in the mink. VIII. A quantitative study of the expression of C gamma-allotypes (H3, H4, H6, H8) in sera. AB - The results of a quantitative study of the expression of mink C gamma-allotypes (H3, H4, H6, and H8) in sera are presented. H6 and H8 were found to be stably expressed, and the individual concentrations of the allotypes varied within one order of magnitude. Gene dosage effects were observed for H6 and H8: average sera allotype concentrations in homozygotes were twice those in heterozygotes. In contrast, the serum concentrations of H3 and H4 varied by three orders of magnitude, ranging from minor (2-200 micrograms/ml) to high (1-10 mg/ml). No gene dosage effects were observed for the expression of H3 and H4. Histograms for the population of H3 concentrations showed three peaks, sharply differing from those of H4, H6, and H8. There was no association between the minor expression of H3 and H4. The data obtained indicate that the expression of mink C gamma-allotypes is regulated by different allotype-specific mechanisms. PMID- 1642903 TI - Complement-mediated killing of susceptible gram-negative bacteria: an elusive mechanism. AB - Exposure of gram-negative bacteria to a source of antibody and complement frequently results in efficient cell killing; this effect follows the deposition of C5b-9 membrane attack complexes onto the bacterial surface. This review examines the molecular and physiological events culminating in C5b-9 deposition and cell death and advances an hypothesis that may account for cytoplasmic membrane damage following complement-mediated perturbation of the outer membrane. PMID- 1642904 TI - Magnetic resonance imaging of meningiomas. AB - MRI with gadolinium enhancement is the imaging modality of choice in the diagnosis of meningiomas. Various MRI features are described. MRI signal intensity characteristics in meningiomas contain information that could be correlated with the histopathology of the tumor. Hyperintensity on T2-weighted images indicates soft tumor consistency and microhypervascularity and is more often seen in aggressive, angioblastic, or meningothelial meningiomas. MRI is useful in demonstrating dural sinus involvement. Meningiomas in unusual locations and their mimics are also presented. PMID- 1642905 TI - Posterior fossa neoplasms: multiplanar imaging. AB - Multiplanar imaging capabilities and increased tissue contrast inherent to MR permit inimitable evaluation of the normal and abnormal structures of the posterior fossa. A review of common posterior fossa neoplasms in adults and children is presented with emphasis on the MR characteristics. PMID- 1642906 TI - Imaging of pituitary gland tumors. AB - MRI has clearly improved the visualization of the perisellar region. Its full role in the diagnosis of pituitary adenomas remains to be defined. It is likely that three-dimensional Fourier transform thin-section imaging of the gland will further refine the diagnosis of adenoma, allowing not only for the visualization of tiny adenomas, but possibly helping to distinguish them from other nonadenomatous intraglandular abnormalities. PMID- 1642907 TI - The development and safe use of patient-controlled analgesia. PMID- 1642908 TI - Fresh gas requirements of an enclosed afferent reservoir breathing system in anaesthetized, spontaneously ventilating children. AB - We have determined the minimum fresh gas flow rate (VF) for use with the Ohmeda enclosed afferent reservoir breathing system (EAR) in 10 anaesthetized children breathing spontaneously. First, we determined the VF required to prevent rebreathing as detected by increased total ventilation (VE) and end-tidal carbon dioxide partial pressure. Second, we used a mathematical model to calculate the degree of rebreathing occurring at each VF. A VF equal to the predicted alveolar ventilation was sufficient to prevent clinically detectable rebreathing in all patients. From the model, no rebreathing occurred when VF/VE was 0.78 or more. We have shown previously that the EAR functions efficiently during controlled ventilation with a VF = 0.6 x weight 0.5. As this VF is slightly greater than the predicted alveolar ventilation, we suggest that the EAR may be used with a VF = 0.6 x weight 0.5 regardless of the mode of ventilation. PMID- 1642909 TI - Extradural clonidine infusions for analgesia after total hip replacement. AB - We have examined the effectiveness of extradural clonidine infusions for postoperative analgesia and the effect of clonidine on extradural morphine. In a double-blind, controlled study, patients, undergoing total hip replacement were allocated randomly to receive one of two doses of extradural clonidine (25 micrograms h-1 or 50 micrograms h-1), low dose extradural morphine or a combination of morphine and clonidine. Pain scores in the morphine group were significantly greater than in the clonidine groups (P less than 0.01) and the combination group (P less than 0.05) during the first 1 h after surgery. The requirements for systemic analgesia were least in the combination and larger dose clonidine group, and the duration of effect of the initial bolus dose was significantly longer compared with the morphine and low dose clonidine groups (P less than 0.05). Arterial pressure was reduced in the clonidine groups, although the incidence of clinical hypotension was low. There were no significant differences between the groups in emetic symptoms or urinary retention. PMID- 1642910 TI - Effect of pre- vs postoperative inguinal field block on postoperative pain after herniorrhaphy. AB - The analgesic effects of an identical inguinal field block, performed before or immediately after inguinal herniorrhaphy, were evaluated in 32 healthy patients in a double-blind, randomized study. During surgery, all patients received a light general anaesthesia with thiopentone, alfentanil and nitrous oxide in oxygen. After induction of general anaesthesia, patients were allocated randomly to receive an inguinal field block with lignocaine, either 15 min before operation or immediately after operation, after closure of the surgical wound, but before the patients were awake. Pain score on a visual analogue scale and on a verbal scale at rest, during mobilization from supine into sitting position and during cough was assessed 1, 2, 4, 6, 8 and 24 h, and 7 days after operation. No significant differences between the groups were observed in VAS scores or verbal pain scores during rest or ambulation at any time. There was no significant difference in time to first request for morphine or total morphine consumption. These results do not show pre-emptive analgesia with a conventional inguinal field block to be of clinical importance compared with a similar block administered after operation. PMID- 1642911 TI - Effect of physiotherapy on the auditory evoked response of paralysed, sedated patients in the intensive care unit. AB - Auditory evoked response (AER) was recorded before, during and after physiotherapy in 11 paralysed (atracurium 0.56 (SD) 0.13 mg kg-1 h-1), sedated (propofol 2.2 (1.0) mg kg-1 h-1; fentanyl 4.4 (2.3) micrograms kg-1 h-1) and critically ill patients undergoing ventilation in the intensive care unit (ICU). The latency of the negative wave, NB, was reduced by physiotherapy (mean 44.8 (SD) 7.9 ms before, 41.0 (6.8) ms during (P less than 0.01, non-parametric Friedman test) and 45.6 (6.3) ms after physiotherapy); NB amplitude showed no consistent change (-0.81 (1.4) microV, -0.81 (1.5) microV and -0.71 (1.3) microV, respectively). NB latency responded to patient arousal at constant levels of sedation and this requires further evaluation as a means of monitoring sedation in paralysed patients in the ICU. PMID- 1642912 TI - Recovery from day-case anaesthesia: comparison of total i.v. anaesthesia using propofol with an inhalation technique. AB - A prospective, double-blind study was conducted to compare postoperative recovery after either total i.v. anaesthesia (TIVA: propofol and alfentanil) or an inhalation technique (propofol and alfentanil followed by nitrous oxide and isoflurane) in 50 patients undergoing day-case gynaecological surgery. Psychomotor performance was assessed at 1 and 2 h after surgery using the Critical Flicker Fusion Threshold (CFFT), Simple Reaction Time (SRT) and Choice Reaction Time (CRT). Subjective recovery and side effects after discharge from hospital were assessed using a postal questionnaire. Recovery occurred significantly earlier in the TIVA group as assessed by CFFT and SRT (P less than 0.01); there were no significant differences (P greater than 0.05) between the two groups in CRT, subjective duration of recovery or side effects. PMID- 1642913 TI - Heart rate periodicities during induction of propofol-nitrous oxide-isoflurane anaesthesia. AB - This study examined the variation in cardiac inter-beat interval during induction of anaesthesia with propofol and subsequent inhalation anaesthesia with nitrous oxide and isoflurane. In comparison with preoperative control values, heart rate variability was reduced by anaesthesia and there was a complex, but consistent, pattern of R-R interval change during induction. Immediately after propofol 2 mg kg-1, high frequency heart rate oscillations were replaced by low frequency oscillations (0.05 Hz). Subsequently, with decreasing propofol and deepening nitrous oxide-isoflurane anaesthesia, high frequency components returned towards, although not reaching, control values; low and, to a greater extent, mid range (0.1-Hz) frequency components remained reduced. We postulate that these alterations are consistent with an immediate but transient post-induction ventilatory depression, subsequent decrease in efferent sympathetic activity and reduction in baroreflex responsiveness. R-R interval analysis is suggested to be a useful tool in the evaluation of autonomic function during anaesthesia. PMID- 1642914 TI - Response of 10 pulse oximeters to an in vitro test system. AB - Pulse oximeters are often used in situations in which severe hypoxaemia may occur. We have developed an in vitro system to test the accuracy of pulse oximeter calibration. The probe of 10 different oximeters was attached to a model finger in an in vitro blood circuit, and pulse oximeter readings (SpO2) were compared with multi-wavelength in vitro oximeter readings (SO2) over a range of SO2 values from 50 to 100%. The oximeters tested varied widely in their accuracy and linearity. We conclude that the system can test the accuracy, reproducibility and linearity of response of pulse oximeter readings at low oxyhaemoglobin saturations. PMID- 1642915 TI - Vasodilator properties of nitroglycerin and isosorbide dinitrate during cardiopulmonary bypass. AB - In a placebo-controlled trial, we have studied the vasodilator properties of bolus doses of nitroglycerin (TNG) and isosorbide dinitrate (ISDN) in 32 patients during cardiopulmonary bypass with a constant pump flow. Blood volume of the venous reservoir and mean arterial pressure were recorded for 10 min after drug administration to detect changes in venous capacitance and arteriolar resistance, respectively. The venous capacitance-increasing effects of TNG 200 micrograms and ISDN 1,600 micrograms were initially identical and significant at 2 and 3 min after the bolus. Thereafter, the effect of TNG began to decline, while that of ISDN remained significant until the end of the study. TNG 200 micrograms decreased arterial pressure slightly more than ISDN 1,600 micrograms, but the effect of both drugs lasted for only 1-2 min. TNG and ISDN were equipotent in increasing venous capacitance when administered in a bolus dose ratio of 1:8 during CPB, but the venodilator effect of ISDN lasted longer than that of TNG. The duration of the arteriolar dilator effect was very short with both drugs. PMID- 1642916 TI - Accuracy of text entries within a manually compiled anaesthetic record. AB - We have examined the accuracy of text entries within a manually compiled anaesthetic record by comparing the record of the anaesthetist with that of an observer, present throughout the procedure but whose sole purpose was the documentation of perioperative events. Eighty-six items of information were analysed for accuracy from 197 records. The mean proportion of omissions was 35% and the mean proportion of incorrect entries was 3.4%. Where no entry should have been made, the mean proportion of unwarranted entries was 1%. Accuracy varied according to the information contained; however, omissions were common for preoperative status, fluids, tourniquet use, aspects of monitoring, local anaesthesia and intraoperative problems. The most consistently accurate information was the description of the patient and that relating to intraoperative i.v. drug use. Inaccuracy was common for the majority of sites on the record, irrespective of their reflecting on the anaesthetist's performance. We suggest, therefore, that the reason for this inaccuracy of data was not related principally to anaesthetists' defensiveness, but may reflect their attitudes to the record's value and response to inadequacies in its design. The observed deficiencies in recording accuracy may affect patient safety during future anaesthesia and has relevance to medico-legal and epidemiological research. PMID- 1642917 TI - Transcranial Doppler sonography: effects of halothane, enflurane and isoflurane on blood flow velocity in the middle cerebral artery. AB - Systolic, diastolic, and mean blood flow velocity in the middle cerebral artery (Vs,mca; Vd,mca; Vm,mca) and pulsatility (Vs-Vd)/Vm of the waveform obtained were recorded in 51 patients before, during and after general anaesthesia. Transcranial Doppler (TCD) sonographic variables were measured in the awake patient and after induction of anaesthesia with thiopentone 5-6 mg kg-1. After tracheal intubation, 17 patients received 0.8% halothane and 66% nitrous oxide in oxygen for 30 min (15 min normoventilation; 15 min hyperventilation). The inspired halothane concentration was then increased to 1.6% for 45 min (15 min normoventilation; 15 min hyperventilation; 15 min normoventilation with nitrous oxide replaced by oxygen). Enflurane (1.7% for 30 min and 3.4% for 45 min) was given to another 17 patients; 17 other patients received isoflurane (1.2% and 2.4%). Mean arterial pressure (MAP), nasopharyngeal temperature, end-tidal carbon dioxide concentration, inspired and end-tidal anaesthetic agent concentrations, haemoglobin concentration, PVC and TCD variables were measured at the end of each 15 min period. After recovery from anaesthesia, TCD variables were measured again. There were no intergroup differences in changes in MAP, nasopharyngeal temperature, haemoglobin concentration and PCV. Halothane, enflurane and isoflurane at low doses and normoventilation had little influence on TCD variables compared with awake values. In large concentrations with nitrous oxide in oxygen and normoventilation, there were differences between the volatile agents. Halothane increased blood flow velocities, but enflurane and isoflurane caused little change. Hyperventilation always decreased blood flow velocities and increased pulsatility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1642918 TI - Rapid administration of crystalloid preload does not decrease the incidence of hypotension after spinal anaesthesia for elective caesarean section. AB - Twenty parturients undergoing elective Caesarean section were allocated randomly to receive crystalloid preload 20 ml kg-1 over either 20 min or 10 min before spinal anaesthesia. Significant hypotension (systolic arterial pressure less than 100 mm Hg and less than 80% of baseline value) occurred in six of the 10 patients in the 20-min preload group and seven of 10 patients in the 10-min preload group (ns). Both groups had a significant (P less than 0.05) increase in central venous pressure during the preload period. The mean central venous pressure in the 10 min group was 11.9 mm Hg (range 6-19 mm Hg), which was significantly greater (P less than 0.05) than that in the 20-min group (mean 7.3 mm Hg, range 2-13 mm Hg). Three patients in the 10-min group had clinically unacceptable increases in central venous pressure. This study has demonstrated that rapid administration of crystalloid preload before spinal anaesthesia did not decrease the incidence or severity of hypotension, and questions the role of crystalloid preload. PMID- 1642919 TI - Anaesthesia and the ventilatory system in infants and young children. PMID- 1642920 TI - Evaluation of a disposable patient-controlled analgesia device in children. AB - A disposable patient-controlled analgesia (PCA) device was evaluated in 20 children after major abdominal, urological and orthopaedic surgery. All patients were given a high dependency level of nursing care in general wards. Efficacy (as assessed by hourly pain scores) was comparable to that achieved in a matched control group of 20 children who used the Graseby PCA system. Safety was confirmed by monitoring arterial oxygen saturation, sedation scores and ventilatory frequency. Morphine consumption was similar with the two techniques, but varied widely between patients. The disposable device has a complementary role to play in the provision of a comprehensive pain relief service for children. PMID- 1642921 TI - Stability of fentanyl, bupivacaine and adrenaline solutions for extradural infusion. AB - Fentanyl and bupivacaine were tested for their stability when diluted with 0.9% sodium chloride to 4 micrograms ml-1 and 0.1% respectively, in 100-ml polyvinyl chloride (PVC) bags, alone and in combination, with and without adrenaline 1:200,000. Changes in drug concentration and pH were investigated for 56 days. The combination of fentanyl, bupivacaine and adrenaline was tested under varying environmental conditions of 35 degrees C, 4 degrees C, -18 degrees C, room temperature, darkness and after autoclaving. Fentanyl and bupivacaine were adsorbed onto PVC, resulting in reductions of 12.6% and 9.6% drug mass, respectively, at day 3, but remained stable thereafter. Adrenaline was progressively degraded to a maximum reduction of 37.3% at 35 degrees C by day 56. Solutions containing adrenaline became more acidic over 56 days. Fentanyl and bupivacaine were stable. PMID- 1642922 TI - Myocardial depressant effect of nitrous oxide after coronary artery bypass graft surgery. AB - We have studied the cardiovascular effects of nitrous oxide after cardiac ischaemia-reperfusion injury caused by aortic cross-clamping and unclamping during coronary artery bypass grafting (CABG). At the time of chest closure, 20 patients were allocated randomly to receive oxygen and air (FIO2 = 0.5) or 50% nitrous oxide in oxygen in addition to anaesthesia with fentanyl. Nitrous oxide significantly decreased mean arterial pressure (P less than 0.01) and cardiac index (P less than 0.05), which suggests that nitrous oxide with fentanyl may significantly depress left ventricular performance after CABG. Although ischaemia reperfusion cardiac injury did not appear to increase the myocardial depressant effect of nitrous oxide, the use of nitrous oxide is not recommended immediately after CABG. PMID- 1642923 TI - Anaesthesia in a parturient with osteogenesis imperfecta. AB - A 20-yr-old primigravida at 38 weeks gestation with premature rupture of membranes and evidence of fetal distress required urgent Caesarean section. The diagnosis of osteogenesis imperfecta had been made 4 days earlier. The patient refused a regional anaesthetic. Difficulties in the administration of general anaesthesia to patients with osteogenesis imperfecta were recognized and managed accordingly. These problems are discussed and the importance of early antenatal assessment of such patients by the department of anaesthesia is emphasized. PMID- 1642924 TI - Change in cerebral blood flow velocity pattern during induced hypotension: a non invasive indicator of increased intracranial pressure? AB - A neurologically intact patient underwent spinal instrumentation under hypotensive anaesthesia 10 days after a mild closed head injury. Transcranial Doppler monitoring of the right middle cerebral artery revealed an abnormal flow pattern, suggesting increased intracranial pressure, impaired autoregulation, or both. Patients with a mild head injury may have altered intracranial haemodynamics and the time course of recovery from these changes is unknown. PMID- 1642925 TI - Extradural diamorphine for postoperative analgesia: audit of a nurse-administered service to 800 patients in a district general hospital. AB - We report the use of extradural diamorphine for postoperative analgesia as a nurse-based service on selected surgical wards in a district general hospital. Eight hundred patients received lumbar or thoracic extradural diamorphine analgesia for postoperative or traumatic pain. Diamorphine was administered in bolus form by suitably trained nursing staff. Satisfactory analgesia, recorded on a verbal rating scale at the conclusion of the service, was achieved in 94.6% of patients. The technique was considered by medical and nursing staff to be a safe and acceptable method of analgesia. Respiratory depression, defined as a ventilatory frequency of less than 10 b.p.m., occurred in seven patients (incidence of 0.9%). All occurred in the theatre recovery area or in the intensive care unit. Retrospectively, each was predictable and all responded to naloxone 0.4 mg. PMID- 1642926 TI - Overdose of opioid from patient controlled analgesia pumps. PMID- 1642927 TI - Combined spinal-extradural anaesthesia. PMID- 1642928 TI - Masseter spasm after suxamethonium. PMID- 1642929 TI - Tension pneumothorax--detection and incidence. PMID- 1642930 TI - Fresh gas utilization in the circle system. PMID- 1642931 TI - Collegiate developments. PMID- 1642932 TI - Liver disease and drug disposition. PMID- 1642933 TI - Effects of different hepatic pathologies on disposition of alfentanil in anaesthetized patients. AB - We have studied the influence of different hepatic pathologies on the disposition of alfentanil in 23 unpremedicated patients (six healthy control subjects, six patients with liver dysfunction of alcoholic aetiology and 11 patients with non alcohol related liver disease). All patients received a bolus of alfentanil 500 micrograms i.v. as supplement to 67% nitrous oxide and isoflurane in oxygen anaesthesia. Plasma drug concentrations were measured in venous blood samples at intervals up to 24 h by radio-immunoassay and protein binding was determined by equilibrium dialysis. Kinetic estimates were determined using non-compartmental analysis. Patients with non-alcoholic liver disease had lesser plasma clearance (114.8 (range 66.8-213.5) ml min-1) than the alcoholic group (158.8 (100.0-220.7) ml min-1) or controls (187.4 (125.2-269.5) ml min-1). In all three groups, there was considerable intersubject variability, with a bimodal distribution in the non alcoholic group. This group also had a smaller apparent volume of distribution at steady state. Mean residence time was prolonged in the alcoholic group compared with controls (284.9 (217.8-362.2) min vs 226.8 (201.2-250) min). Protein binding was decreased in the alcoholic group compared with controls (84.9 (SD 4.2)% vs 89.3 (2.1)%); this was attributable to a lesser plasma alpha 1-acid glycoprotein concentration (0.55 (0.18) g litre-1 vs 0.89 (0.21) g litre-1). Free drug clearance was reduced in both liver dysfunction groups compared with controls. PMID- 1642934 TI - Relationship between hypoxaemic and cardiac ischaemic events in the perioperative period. AB - We have used continuous and concurrent monitoring of arterial oxygen saturation (SpO2) and ECG to study the relationship between hypoxaemia and silent myocardial ischaemia in the perioperative period in 11 patients with cardiovascular disease. Ischaemic and hypoxaemic events occurred in all patients. Many events were shortlived and occurred independently of each other. However, our results suggest a close correlation between the duration of hypoxaemia and myocardial ischaemia. Ischaemia is more likely to occur if an episode of hypoxaemia is prolonged (beyond 5 min; P less than 0.01, chi square) and severe (SpO2 less than 85%; P less than 0.05, chi square). PMID- 1642935 TI - IV diclofenac in post-thoracotomy pain. AB - We have studied the efficacy of a continuous i.v. infusion of diclofenac 2 mg kg 1/24 h given for 2 days after major thoracic surgery in 30 patients in a double blind, placebo-controlled, parallel-group design. The patients were able to obtain additional pain relief as on demand morphine boluses. In the diclofenac group, the consumption of morphine was reduced by 60% during the first and by 76% during the second day after operation compared with the control group. Overall, analgesia was also superior in the diclofenac group. Arterial oxygenation was significantly greater and the arterial PCO2 increased less during the first day after operation in the diclofenac group compared with the control group. Diclofenac had no significant effect compared with placebo on blood loss or on any bleeding or platelet test. Urine output was significantly less during the first day after operation in the diclofenac group compared with the control group, but was normal on the second day after operation; plasma creatinine concentrations were unchanged. I.v. diclofenac infusion combined with opioids delivered via a patient-controlled analgesia device seems a valuable method of pain relief after thoracic surgery in patients in whom more invasive techniques, such as extradural local anaesthetics and opioids, cannot be used. However, non steroidal anti-inflammatory drugs should be used cautiously, if at all, in patients who are at risk of acute renal failure. PMID- 1642936 TI - Effects of ketorolac trometamol on renal function. AB - We have compared the renal effects of ketorolac trometamol 10 mg administered 4 hourly by intermittent i.m. injection or by continuous i.m. infusion with placebo in a double-blind study in 67 patients who had undergone upper abdominal surgery. Ketorolac was supplemented during the 48-h postoperative study period with bolus doses of morphine delivered by a patient controlled analgesia system. The only significant effect of ketorolac on renal function compared with patients who received placebo was reduced excretion of potassium. The overall changes caused by surgery alone were of much greater magnitude. Bleeding time was increased with ketorolac, but there were no adverse events related to this. PMID- 1642937 TI - Pharmacokinetics of propofol during and after long-term continuous infusion for maintenance of sedation in ICU patients. AB - The pharmacokinetics of propofol administered as long term infusions were determined in 12 intensive care unit patients (two female; mean age 58 yr, mean weight 66.9 kg) requiring sedation during mechanical ventilation. Patients were recruited after having been administered propofol for 24 h. Blood samples for analysis of propofol were taken during the infusion (mean duration 85.6 h; mean rate 2.58 mg kg-1 h-1) and for up to about 42 h after its termination. The median propofol total body clearance, derived from the apparent steady state propofol blood concentrations during infusion, was 2.11 litre min-1. One patient died during the infusion, from multi-organ failure secondary to a pre-existing septicaemia, and in one other patient no sampling was possible during the first 30 min after infusion; full elimination data were obtained for 10 patients. After termination of the infusion, propofol blood concentrations declined rapidly, with an overall mean decrease of 50% over the first 10 min; thereafter the decline was more gradual. The elimination profile was triphasic in seven patients and biphasic in three patients. Mean half-lives for the three phases were 1.81 (n = 10) min, 70.9 (n = 7) min and 1411 (n = 11) min. There was no apparent trend in the terminal phase half-life with the duration of sampling after infusion. PMID- 1642938 TI - Use of mivacurium chloride by constant infusion in the anephric patient. AB - Twenty anephric and 20 healthy patients received a bolus dose of mivacurium 150 micrograms kg-1. When the first EMG response (T1) of the train-of-four had recovered to 5% of control (T0), an infusion of mivacurium 10 micrograms kg-1 min 1 was started and adjusted to keep T1 at 5%. Ten patients in each group were given neostigmine 35 micrograms kg-1 when the infusion was stopped when T1/T0 had recovered to 20%; in the others recovery was spontaneous. After the bolus dose of mivacurium, mean (SD) depression of T1 was greater in the anephric group than in the normal group (98.4 (3.5) vs 96.8 (4.4)%; P less than 0.01) and recovery of T1/T0 to 5% was slower (15.3 (6.9) vs 9.8 (3.5) min; P less than 0.01). Anephric patients required a slower infusion rate (6.3 (1.9) vs 10.4 (2.8) micrograms kg-1 min-1; P less than 0.001). Neostigmine hastened recovery of both T1/T0 and T4/T1 in both groups. Spontaneous recovery of T1/T0 (from 25% to 75%) after the infusion was also slower in anephric patients (12.2 (8.2) vs 7.7 (1.2) min; P less than 0.05). Plasma cholinesterase activity was less in the anephric group (785 (207) vs 943 (217) iu litre-1; P less than 0.05) and there was a (negative) correlation overall between cholinesterase activity and time to 5% recovery of T1/T0 after the bolus dose (r = -0.42; P less than 0.02). We conclude that patients with chronic renal failure may require a reduced dose of mivacurium. PMID- 1642939 TI - Gastroduodenal dysfunction as a cause of gastric bacterial overgrowth in patients undergoing mechanical ventilation of the lungs. AB - We have studied 15 patients undergoing mechanical ventilation of the lungs for evidence of a relationship between gastroduodenal dysfunction and gastric bacterial overgrowth. Duodenal reflux was detected by quantitative measurement of conjugated bilirubin in gastric aspirate specimens. The pH and bacterial content of these specimens were analysed. A minority of specimens with pH less than 3.5 contained measurable numbers of viable bacteria. The total bacterial count and the count of Gram negative bacteria correlated significantly with specimen pH in both cases (P less than 0.001, in both). In the 72 specimens of gastric aspirate with pH greater than 3.5, the presence of Gram negative bacteria was associated significantly with detectable bilirubin (P less than 0.001). The total bacterial count was greater also in specimens containing bilirubin (P = 0.009). These results suggest that gastroduodenal dysfunction may promote gastric bacterial overgrowth, contributing to the development of ventilator-associated pneumonia. PMID- 1642940 TI - Effect of low and high concentrations of alfentanil administered intrathecally on A delta and C fibre mediated somatosympathetic reflexes. AB - We have studied the effects of alfentanil administered intrathecally on somatosympathetic reflexes evoked by stimulation of radial and tibial nerves in 10 anaesthetized and paralysed dogs. In five animals, alfentanil was administered in doses of 100, 100, 200 and 400 micrograms in 0.8 ml and 800 micrograms in 1.6 ml prepared from the formulation of 500 micrograms ml-1. Five others received alfentanil (high concentration formulation, 5 mg ml-1) in doses of 500 and 2000 micrograms in 0.5 ml and 5000 micrograms in 1 ml. C fibre tibial nerve reflexes were depressed by 100 micrograms and abolished with doses of 200-400 micrograms, but the A delta response remained unaffected. A delta responses were depressed also and abolished, respectively, by doses of alfentanil 2000 micrograms and 5000 micrograms. At the larger, but not the smaller, concentration there was evidence of baroreflex sensitization probably caused by systemic absorption of the drug. PMID- 1642941 TI - Somatosensory and auditory evoked responses recorded simultaneously: differential effects of nitrous oxide and isoflurane. AB - Auditory (AER) and somatosensory evoked responses (SSER) were recorded simultaneously in eight patients under anaesthesia before surgery. We studied the effects of equi-MAC end-expiratory concentrations of isoflurane (0.65-0.75%) and nitrous oxide (60-65%). The anaesthetics were changed at random in three consecutive 10-min periods so that each patient received both drugs. From the AER recorded from the vertex and inion, Pa and Nb latency and amplitude were measured. N13, P20 latency and N13 amplitude were measured from SSER recordings from the neck and P15, N20, P25, N35, P45 latency and P15-N20, N20-P25, P25-N35 and N35-P45 amplitude from the scalp over the hand area of the sensory cortex. Compared with nitrous oxide, isoflurane significantly increased the latencies of the AER waves Pa (P = 0.02) and Nb (P = 0.02), and the SSER waves N20 (P = 0.001) and P25 (P = 0.04). We were unable to demonstrate significant differences in Pa and Nb amplitude between isoflurane and nitrous oxide that we had seen previously. However, the amplitude of the SSER wave N20 was reduced significantly by nitrous oxide compared with isoflurane (P = 0.0004). This wave (N20) is thought to emanate from the thalamo-cortical radiations, and our findings may be explained by an analgesic effect of nitrous oxide mediated by endogenous opioids. PMID- 1642942 TI - Voltage fields surrounding needles used in regional anaesthesia. AB - Using a bench model, we have studied the voltage fields surrounding both insulated and uninsulated needles used in regional anaesthesia. The findings were compared with earlier computer predictions which suggested that the fields would be markedly different for the two types of needle. The results confirm that the fields differ markedly and suggest that the use of insulated needles may not necessarily improve the accuracy of nerve location and that uninsulated needles may be more appropriate. PMID- 1642943 TI - Arterial oxygen saturation during induction of anaesthesia and laryngeal mask insertion: prospective evaluation of four techniques. AB - In a prospective, randomized study of 87 patients, we have compared the incidence of hypoxaemia during induction of anaesthesia with subsequent Laryngeal Mask Airway (LMA) insertion in healthy adults when four different techniques were used: one without supplementary oxygen, and three with supplementary oxygen. Twelve patients did not receive supplementary oxygen before LMA placement, 25 underwent partial denitrogenation by breathing oxygen from the start of injection of the induction agent, 25 underwent formal denitrogenation by breathing oxygen for 3 min, and 25 received five tidal volume breaths of oxygen by face mask using positive pressure immediately after induction of anaesthesia. Anaesthesia was induced with propofol 2.0 mg kg-1 and fentanyl 1 microgram kg-1. Additional propofol was given if required. Arterial oxygen saturation was measured by pulse oximetry. Desaturation occurred in 11 of 12 patients who did not receive supplementary oxygen, and in 19 of 25 patients who received manual ventilation with 100% oxygen after induction of anaesthesia before LMA insertion. Full denitrogenation and partial denitrogenation were equally successful in preventing desaturation. Failure to position the LMA successfully occurred in 3% of patients, and some difficulty was encountered in another 18%. PMID- 1642944 TI - Does glycine antagonism underlie the excitatory effects of methohexitone and propofol? AB - We have investigated the pharmacological basis of CNS excitation that occurs in association with general anaesthesia in mice. Propofol produced sustained clonic movements during anaesthesia. Methohexitone produced intermittent non-rhythmic jerking during anaesthesia. Ethanol and pentobarbitone produced anaesthesia without associated clonic movements. Doses of all anaesthetic drugs were equipotent. Surface EEG recordings showed paroxysmal discharges consistent with interictal manifestations of cortical seizures with methohexitone or propofol, but not with ethanol or pentobarbitone. Strychnine, a glycine antagonist without effects on the cerebral cortex, and bicuculline, a GABAA antagonist with effects on the cerebral cortex, were used in doses that were equipotent-0.5 log units less than the ED10 for clonic convulsions. Strychnine potentiated both excitatory behaviour and EEG paroxysmal discharges when given with methohexitone or propofol, but not with ethanol or pentobarbitone. Bicuculline did not affect either behaviour or EEG with any of the anaesthetic drugs. Our data show that methohexitone and propofol produced CNS excitation, while pentobarbitone and ethanol did not. We propose that the pharmacological basis of this excitation may be glycine antagonism occurring in subcortical structures. PMID- 1642945 TI - Esmolol hydrochloride for management of the cardiovascular stress responses to laryngoscopy and tracheal intubation. AB - In a double-blind, randomized, controlled prospective study, 30 grade ASA I/II patients received a continuous i.v. infusion of normal saline or esmolol hydrochloride before induction of anaesthesia and tracheal intubation. Arterial pressure and heart rate were measured to assess the pressor response to laryngoscopy and intubation. The heart rate decreased in the esmolol group before induction of anaesthesia. The pressor response to laryngoscopy was significantly less marked in the esmolol group. PMID- 1642946 TI - Reflective blankets used for reduction of heat loss during regional anaesthesia. AB - We have studied the ability of reflective blankets to reduce net loss of body heat during regional anaesthesia for total hip arthroplasty. Thirty patients were allocated randomly to either the study group (insulated with reflective blankets) or the control group (no reflective blankets). Surgical and operation room draping, theatre temperature and i.v. fluid administration were standardized for all patients. Total body heat was deduced from core temperature (aural canal) and mean skin temperature (four measuring sites). After 2 h of surgery, loss of body heat was reduced significantly in patients wrapped in reflective blankets (26 kJ) compared with those in the control group (95 kJ). PMID- 1642947 TI - Airway management in a case of neck impalement: use of the oesophageal tracheal combitube airway. AB - A patient presented with neck impalement after a traffic accident. Respiratory arrest demanded immediate tracheal intubation, which was impossible as a wooden splinter had partially obstructed the pharynx and prevented laryngoscopy. An oesophageal tracheal Combitube airway was inserted successfully and the patient's lungs were ventilated adequately until tracheotomy was performed. PMID- 1642949 TI - Peak serum bupivacaine concentration. PMID- 1642948 TI - Efficiency of the left ventricle assist device Hemopump in cardiac fibrillation. AB - We have examined in sheep the efficiency of the Hemopump during ventricular fibrillation. Circulatory arrest was induced by electrical stimulation and maintained for 30 min. Haemodynamic measurements were recorded continuously and blood samples were taken before, during and after fibrillation to determine total body and myocardial metabolic activity. All hearts were defibrillated successfully after 30 min of fibrillation. During fibrillation, the Hemopump sustained a mean arterial pressure of about 60 mm Hg with a blood flow rate of about 2.3 litre min-1. These perfusion conditions were sufficient for maintenance of aerobic myocardial metabolism, but with a borderline circulatory supply to the total organism. PMID- 1642950 TI - Papers presented at a symposium to honor Dr. Rudolf Nieuwenhuys' 65th birthday. PMID- 1642951 TI - Twenty-five years of comparative neuroanatomy in Nijmegen: homage to Rudolf Nieuwenhuys. PMID- 1642952 TI - Comparative aspects of cerebellar organization. From mormyrids to mammals. AB - Recent progress in the comparative analysis of the vertebrate cerebellar organization shows that the cerebella of different tetrapods have a basically similar intrinsic organization, whereas the cerebellum of fishes displays a number of fundamental differences in this respect. Clear examples of teleostean cerebellar specializations are present in the gigantocerebellum of mormyrids, including a valvula cerebelli, the absence of a parasagittal zonal organization, the presence of eurydendroid projection neurons instead of deep cerebellar nuclei, a precerebellar nucleus lateralis valvulae, olivocerebellar fibers that do not climb into the molecular layer, uni- and bilateral locations of granule cells, parallel fibers without a T-shaped bifurcation and with a coextensive distribution in the transverse plane, and different Purkinje cell arrangements including a dendritic palisade pattern. A theoretical exploration of the possible significance of these configurations suggests that they all might be involved in a single main cerebellar function, i.e. coincidence detection of parallel fiber activity by Purkinje cells. PMID- 1642953 TI - Brain and behaviour: morphological and functional aspects of the hypothalamus in the rat. AB - In a short historical overview some developments in the behavioural research of the hypothalamus of the rat are introduced. Especially the ventromedial and the lateral hypothalamus have received much attention in the past. Numerous different behavioural effects have been described as the result of some kind of activation or inactivation of parts of the hypothalamus in the rat. Questions concerning the topographical distribution and the specificity of the effects observed, are addressed in the later parts. These behavioural observations were very important for the comparison with our anatomical observations concerning the hypothalamus, including the topographical organization of some afferent and efferent relationships. Non-synaptic or paracrine communication may play an important role in the hypothalamic effects on the organization of behaviour. PMID- 1642954 TI - The emotional motor system. AB - A large number of new descending motor pathways to caudal brainstem and spinal cord have been recognized recently. Nevertheless all the new pathways seem to belong to one of three motor systems in the central nervous system (CNS). This survey gives an overview of the pathways belonging to the so-called emotional motor system or the third motor system as defined by Holstege. The similarities and differences with the core, median and lateral paracore areas of the CNS as defined by Nieuwenhuys are discussed. PMID- 1642955 TI - The morphology of the cerebellum the last 25 years. AB - Advances in our knowledge of the subdivision and the development of the cerebellum during the last 25 years are reviewed. It is concluded that the longitudinal subdivision of the cerebellum has become firmly established in studies of the morphogenesis, the connections and the chemoarchitecture of the cerebellum. A complicated relationship exists between the transverse, lobular subdivision of the cerebellum and the distribution of different mossy fiber systems. PMID- 1642956 TI - Development of motor systems: a comparative approach. AB - Anurans offer a unique opportunity to study the development of neuronal connections. Transition from the aquatic limbless tadpole to the juvenile occurs over a protracted period of time during which the animal is accessible for experimental studies. Moreover, tract-tracing studies have demonstrated that their descending brain stem pathways show remarkable similarities in origin, course and site of termination to those of mammals. A developmental sequence in the formation of descending pathways to the spinal cord has been shown implying that reticulospinal and vestibulospinal fibers innervate spinal segments very early in development, whereas the red nucleus projects spinalwards definitely later in development. In anurans, this developmental sequence parallels the changes observed in locomotor pattern. The ingrowth of descending pathways into the spinal cord possibly occurs along so-called 'pre-existing' tracts. Several hypotheses on guidance cues in axonal pathfinding will be discussed. PMID- 1642957 TI - Psychosocial predictors of "safer sex" behaviors in young adults. AB - This study tested a model of safer sex behavior using variables from social learning theory, the health belief model, the theory of reasoned action, and theories of cognitive coping style. Two types of safer sex behavior were measured: frequency of condom use and the discussion of AIDS and past partners with a sexual partner. The participants--275 undergraduate students--completed an anonymous written questionnaire. The variables (behavioral intention, perceived susceptibility, barriers, self-efficacy, monitoring, blunting, and social support) predicted 35% of the variance in condom use and 13% of the variance in discussion (adjusted R2s). Intention was the strongest predictor of both types of safer sex behavior. Perceived susceptibility and perceived barriers were associated with intention to use a condom; perceived barriers was inversely related to condom use. Self-efficacy was associated with the intention to discuss and reported discussion of AIDS and past partners with a sexual partner; social support was related to the intention to discuss. An information-avoiding coping style was negatively associated with condom use. Implications for future research and intervention efforts in the area of AIDS prevention are discussed. PMID- 1642958 TI - Factors associated with urban gay men's treatment initiation decisions for HIV infection. AB - While a public health emphasis on primary prevention of human immunodeficiency virus (HIV) infection continues, it is recognized that large numbers of individuals are already infected. Efforts at secondary prevention focus on early medical intervention and may be effective in slowing progression to a diagnosis of AIDS. Understanding the factors that promote or impede seropositive individuals from receiving prompt medical treatment and complying with treatment regimens is essential to prolonging survival. During unstructured interviews in an ongoing study of sexual decision-making, 55 urban, gay, seropositive men spontaneously offered information about their treatment choices for their HIV infection. Findings regarding their considerations in initiating, delaying, or rejecting medical treatment are presented. PMID- 1642959 TI - Targeting the audience for AIDS messages by actual and perceived risk. AB - Since there are many ways to segment an audience into target groups, we suggest that a productive strategy for AIDS education is to divide the audience by their actual and perceived risk. We provide an example in which we segmented an urban U.S. sample and make suggestions as to how messages appropriate for each group can be constructed. In our sample, the "unthreatened" accurately assessed their low risk of AIDS, and showed high knowledge and tolerance rates. The "panicked," who included more women and Hispanics, inaccurately thought themselves at high risk because of misunderstandings about the causes of AIDS, and showed more intolerance of people with AIDS. "Deniers" continued to have multiple sexual partners and take precautions irregularly, despite seeing AIDS as a social problem and having more education and AIDS knowledge. In contrast, "gamblers" recognized their higher risk of AIDS and were most likely to have taken some action, although not enough to prevent sexual transmission of the HIV virus. PMID- 1642960 TI - AIDS education of college students: the effect of an HIV-positive lecturer. AB - Seventy-five introductory psychology students participated in an experiment to assess the effectiveness of 2 types of AIDS education. In the "disclosed" and "undisclosed" conditions, students were given a lecture about AIDS/human immunodeficiency virus (HIV) by a person who has been diagnosed with HIV disease. The lecturer revealed his HIV status in the disclosed but not in the undisclosed condition. A control group received no education. Significant differences were found in a 3 x 3 (Time x AIDS Education) analysis of variance. Knowledge and Attitude posttest scores were significantly higher than pretest scores. Students in the disclosed condition scored higher than students in the control condition on both Knowledge and Attitude posttests. For Behavioral Intent, students in the disclosed condition scored higher than students in the control condition. Subjective comments made by the students indicated that a lecturer with HIV disease had a dramatic impact on their perceptions about AIDS. PMID- 1642961 TI - Alternate forms of HIV prevention attitude scales for teenagers. AB - The purpose of this study was to develop valid, alternate-form scales to measure teenagers' attitudes toward prevention of the transmission of human immunodeficiency virus (HIV). Using a three-component attitude model, a two-way table of specifications was constructed as a theoretical framework for generating attitudinal items relevant to HIV and HIV prevention. Thus, a large pool of Likert-type items was generated, reviewed for clarity and content validity, and prepared for the preliminary scale with 50 items. The scale was administered to 210 high school students. As a result of extensive analyses, two alternate forms with 15 items each were developed. The two forms were simultaneously administered to a sample of 600 high school students. The collected data were subjected to item analyses, factor analysis, and reliability estimation. The results of the analyses provided strong evidence of internal consistency, content validity, and comparability of both forms. The alternate reliability across the form was .82. The alpha reliability coefficients for forms A and B was .78 and .77 and the split-half .76 and .69, respectively. It is concluded that these alternate forms produce valid, reliable, and comparable results for measuring teenagers' attitudes toward HIV prevention. These forms are ideal for pretest/posttest designs used for evaluating educational approaches to HIV control. PMID- 1642962 TI - HIV risk behavior in drug users: increased blood "booting" during cocaine injection. AB - The practice of "booting" or "kicking," in which blood is drawn into the syringe and then injected, was assessed as a possible behavioral mechanism contributing to cocaine's association with increased human immunodeficiency virus (HIV) infection. Intravenous drug users (IVDUs) (N = 68) demonstrated (with an empty, needleless syringe) their usual style of injection of cocaine, heroin, and speedball, in random order. The experimenter recorded the injection procedures and the syringe volumes at each step. Total blood volumes and number of pumps of the syringe were each greater during simulated cocaine and speedball use than during heroin use (p less than .05); means for both cocaine and speedball were 2- to 3-fold greater than for heroin. Subjects also described the booting behavior of their needle-sharing partners; the percentage having partners who booted blood was significantly greater during cocaine use than during heroin use (p less than .05). These findings indicate that cocaine use is associated with a behavioral style of injection (increased blood booting) that is more likely to contaminate the injection equipment with blood. Thus, the practice of booting may warrant special attention in AIDS prevention interventions and risk assessments. PMID- 1642963 TI - Issue dedicated to the memory of John L. Martin, PhD, MPH (1953-1992). PMID- 1642964 TI - Stereoselective aliphatic hydroxylation of 6-n-propylchromone-2-carboxylic acid by female Dutch rabbits. AB - 6-n-Alkylchromone-2-carboxylic acids are metabolized solely by aliphatic oxidation. In the rabbit, the 6-n-propyl congener (PCCA) undergoes omega-1 hydroxylation exclusively. Following administration of PCCA to female Dutch rabbits (500 mumol/kg), some 77% of the dose was excreted in the urine, 41% as PCCA and 36% as 6-(2'-hydroxy-n-propyl)chromone-2-carboxylic acid. Since this metabolite is chiral, we have examined the stereochemistry of the excreted material. Diastereoisomeric (as camphanate and alpha-methoxy-alpha-(trifluoro methyl)phenylacetate esters) and direct chiral HPLC and chiral lanthanide shift NMR have each shown the S:R ratio of the excreted metabolite to be 76:24. When rabbits were dosed with the racemic metabolite, excretion of the compound was not stereoselective. The regio- and stereo-selectivity of the aliphatic hydroxylation of PCCA are thus reflections of the selectivities of the enzyme systems responsible for its formation and suggest PCCA to be an appropriate probe compound for the study of prochiral-chiral hydroxylations. PMID- 1642965 TI - Stereoselective effect of phenprocoumon enantiomers on the binding of benzodiazepines to human serum albumin. AB - The effect of phenprocoumon enantiomers on the stereoselective binding of 3 substituted 1,4-benzodiazepines to human serum albumin (HSA) was studied by chromatography on HSA-Sepharose column. (S)-Phenprocoumon exerts stereoselective allosteric interaction on the binding of benzodiazepines. The structural requirements of enhanced stereoselectivities are similar to those found previously with (S)-warfarin. PMID- 1642966 TI - Rootworm pheromones: the root of a stereochemical mixup. PMID- 1642967 TI - General features of systemic effects of murine leukemias on phosphate metabolism in liver studied by 31P NMR. AB - 31P NMR was used to study the systemic effects of a tumor on a host organism by monitoring the phosphate metabolite content in freshly excised mouse liver at 0-4 degrees C and in ethanolic liver extracts of animals suffering from La, L1210 and P388 leukemias and Ehrlich ascites tumor (EAT). The progression of murine leukemia is characterized by increases in the intensities of the resonances of Pi and phosphomonoesters (PME), in particular, phosphorylethanolamine, in liver; phosphodiester (PDE) signals increase two- to four-fold during the period of rapid tumor growth and decline to undetectable levels in the terminal stage. There were no reliable alterations detected in the ATP content and intracellular pH throughout the course of the leukemia. The kinetics of intracellular phosphates are similar in various kinds of leukemia but quite different in EAT. The reduction of inoculum causes the appearance of maxima in the Pi and PME profiles in the latent period of La leukemia, but the profiles of liver PDE considered from the end of the latent period are independent of inoculum. Possible mechanisms for the changes in PDE concentrations and their biochemical role are discussed. NMR spectroscopy of liver may be used to indirectly monitor the progression of tumors unavailable for direct NMR assay. PMID- 1642968 TI - An in vivo 19F NMR study of isoflurane elimination as a function of age in rat brain. AB - In vivo 19F NMR at 4.7 T has shown that the biphasic elimination of the vapor anesthetic isoflurane from rat brain is ca 15% slower in old (23-24 months) animals compared with young (5-6 months) animals. The fast kinetic component has a t1/2 of ca 7-9 min and the slow event, 100-115 min. Gas chromatographic measurement of arterial blood elimination displays age attenuation to the same extent, although a monophasic kinetic process (6-7 min). The slow wash-out from brain is thought to involve elimination from intracranial fatty tissue as postulated by others in rabbit brain. Longitudinal relaxation time measurements show monoexponential recovery and essentially identical values for young (1.09 + 0.11 s) and old (1.04 +/- 0.09 s) animals. For dipalmitoylphosphatidylcholine vesicles the monoexponential recovery also suggests rapidly exchanging averaged homogeneous lipid environments for the anesthetic, but the longer T1s (2.75 +/- 0.25 s) imply less restricted mobility compared with brain. Single T2 values were obtained in vivo, indicating either a single compartment or rapid exchange between multiple environments. These measurements were inconsistent, undoubtedly as a result of B1 inhomogeneity. The age-attenuated elimination kinetics for isoflurane are consistent with poorer cardiopulmonary function, whereas the T1 data suggest similar environments for the anesthetic in young and old brain tissue. PMID- 1642969 TI - 31P NMR spectroscopy of a xenografted hypopharynx carcinoma: effects of tumor growth and treatment with cisplatin on the tumor phosphorus metabolism, histology and cytokinetics. AB - A xenografted hypopharynx carcinoma growing subcutaneously in nude mice was studied by in vivo 31P NMR spectroscopy during uninfluenced growth and following treatment with cisplatin (CDDP). Parallel to the NMR experiments, the cytokinetic and histological changes in the tumor were investigated. The most significant change in the growing tumor was a decline in the level of phosphocreatine (PCr), whereas the tumor pH did not change. Following treatment with CDDP (4, 8 and 12 mg/kg), a dose-dependent decrease in the level of phosphomonoesters (PME) took place, whilst no dose dependence could be observed for the increase of PCr. the pH shifted to alkaline only after administration of the highest CDDP dose. Tumor cytokinetics revealed a cell arrest at the G1/S boundary 24 h after chemotherapy. At this time, the histological sections showed a dilatation of capillaries, whereas first necroses appeared on day 3. The proliferative activity of the tumor showed a sharp decline 24 h after CDDP application, followed by a revival of cell proliferation that was proportional to the dose applied between days 5 and 7. This increase in proliferative activity was paralleled by a marked increase in the PME/phosphodiesters ratio. Thus, in the tumor investigated the PME were the best indicators of tumor response to therapy. A precise correlation between the cytokinetic data and the re-energization of the tumor was not possible because histological changes, which may contribute to improved tumor energy status took place at the same time. PMID- 1642971 TI - Threshold voltages for hyperbolic secant inversion pulses. AB - Spin inversion produced by hyperbolic secant RF pulses is independent of pulse amplitude once a threshold value is exceeded. A semi-empirical formula for these pulses has been derived by application of analytical solutions to the Bloch equations. This predicts the required coil voltages for inversion as a function of inversion bandwidth and side-to-width parameter mu, based on knowledge of a reference voltage for the loaded coil. The voltage required is shown to increase linearly with bandwidth but to fall with the mu, approximately as (1/mu)0.4. Experimental confirmation is presented, and factors affecting choice of pulse parameters are discussed. PMID- 1642970 TI - Quantitation of metabolites in NMR spectra from isolated tissues, using 14N spectroscopy and nitrate to determine tissue volume. AB - Quantification of metabolites is a goal of many biomedical NMR studies. To obtain absolute measurements of metabolite concentrations is often both difficult and time-consuming. In this paper a method for determining metabolite concentrations directly is described and validated. It is applicable to studies of amphibian muscles, and with suitable precautions, to other isolated organs and tissues. The method is based upon using 14N NMR and nitrate-containing solutions to determine what fraction (F) of the sensitive volume of the RF coil is occupied by tissue. As the concentration of nitrate is known it can be used to calibrate other 14N metabolites in the tissue. Moreover, once F is determined, it can be used to calibrate metabolites in spectra from other nuclei e.g., 31P or 31C. All that is required is that a spectrum from a standard for that nucleus is obtained. Thus this method does not require any 'internal' (intrinsic to the tissue) standard, and is extremely quick and simple to use. PMID- 1642972 TI - 31P NMR spectroscopy of perinatal hypoxic-ischemic brain damage: a model to evaluate neuroprotective drugs in immature rats. AB - Cerebral energy metabolism can be measured non-invasively in unanesthetized neonatal rats with 31P NMR spectroscopy. Using this technique, serial changes in high energy phosphates were determined from the right cerebral hemispheres of 7 day postnatal rat pups during a hypoxic-ischemic insult known to produce focal brain injury. During 3 h of hypoxia-ischemia the concentration of ATP dropped to 33 +/- 8% of prehypoxic (baseline) levels, phosphocreatine (PCr)/Pi decreased from 1.5 +/- 0.51 to 0.16 +/- 0.06, while pH decreased nominally by 0.2 units. After 2.5 h of recovery in air, ATP returned to 75 +/- 10% of baseline levels, PCr/Pi rose to 1.1 +/- 0.28, and pH returned to its normal value of 7.16 +/- 0.06. This model was used to test the efficacy of the adenosine deaminase inhibitor, 2-deoxycoformycin (DCF) as a potential neuroprotective drug. The data for the drug- and saline-treated populations were analyzed by integrating ATP and Pi/PCr levels over specific time intervals, expressing it relative to baseline levels, and modeling it with cubic splines. Pretreatment with 500 micrograms/kg DCF shows a small, but statistically significant, preservation of both ATP and phosphorylation potential during hypoxia and initial recovery. Brain water content (edema) at 42 h recovery was apparently associated with both mean ATP and mean Pi/PCr in the last 2 h of hypoxia-ischemia. When ATP fell below 70% of baseline, brain edema was evident at 42 h of recovery. This methodology is suitable for extension to human infants. PMID- 1642974 TI - Acquired immunodeficiency syndrome (AIDS)--data as at 1 July 1992. PMID- 1642973 TI - Depth selective quantification of phosphorus metabolites in human calf muscle. AB - We have used phase modulated rotating frame imaging, a depth selective NMR technique, in conjunction with two methods of calibration, in order to determine the feasibility of quantifying phosphorus compounds in selected regions of a biological sample. In one method, we related peak areas obtained from a sample to the peak area of an external reference located within the receiver coil, previously calibrated against a standard. In the second method we measured peak areas from a standard separately and related them directly to the area of the sample peak. We examined the calf muscles of male volunteers, positioning the coil to obtain signal mainly from the gastrocnemius in the shallow slices and soleus in the deep slices. The concentrations of Pi, phosphocreatine and ATP (in mmol/kg tissue) were 3.0 +/- 0.5, 18 +/- 2 and 4.8 +/- 0.2 at 2 cm depth (mean +/ SD; n = 5). These results are similar to published biopsy data. A comparison with published values obtained from other NMR quantification methods suggests that, while it is possible to obtain consistent results within one laboratory, it is not currently possible to obtain similar results between laboratories. This is evident from the fact that different laboratories report different phosphocreatine/ATP ratios, indicating that the techniques are limited by variations in the processes of data collection and peak area measurement. PMID- 1642975 TI - World AIDS cases: update. PMID- 1642976 TI - Insurance policies for health care workers with HIV infection. PMID- 1642977 TI - Thrush prophylaxis in AIDS and ARC. PMID- 1642978 TI - Skill mix. Value for money or dilution of care? PMID- 1642979 TI - Skill mix. Does fewer mean better? PMID- 1642980 TI - NHS reforms: blurring the boundaries. PMID- 1642981 TI - Ocular injuries in squash competitors. AB - Squash players are liable to suffer serious eye injuries if they do not take appropriate protective measures. The author presents a short case study which illustrates the type of injury that can be sustained, and argues that nurses and interested associations must become involved in health education activities to reduce the high incidence of injuries during squash matches. PMID- 1642982 TI - The current profile of the profession. PMID- 1642983 TI - Mental health: meeting needs with case management. AB - Present structures encourage a service-led provision of care. The purchaser provider split does have the advantage of targeting those most in need and of promoting an individualised service led by client needs. For those with a long term mental illness, however, a rigid split does not allow multiple needs to be met comprehensively, nor does it allow the work of engaging clients with appropriate services to be based on direct care. Case management is suggested as a flexible means of overcoming these problems. PMID- 1642984 TI - Reviewing options to hysterectomy. AB - The author reviews the options for women for whom hysterectomy has been advised. Nurses working in the community are identified as key personnel in offering such women skilled counselling and advice. This article provides nurses with information on the alternative treatment methods available. PMID- 1642986 TI - Studying at University of Birmingham. PMID- 1642985 TI - Open learning in occupational health. PMID- 1642987 TI - As nurses we must do all we can to identify with our patients. PMID- 1642988 TI - Computing: learning to love bytes. PMID- 1642989 TI - Psychiatry: observing the Italian job. PMID- 1642990 TI - Community care: suffering acts of omission. PMID- 1642991 TI - The Sister Susie column. Starting Susie's way. PMID- 1642992 TI - Ethics: killing or allowing to die? PMID- 1642993 TI - Social security benefits [continuing nursing education]. AB - There is a wide range of benefits available for patients, clients and carers, and, in April this year two new benefits for disabled people were introduced together with new ways of claiming them. Is a knowledge of benefits necessary for a few nurse specialists only, or is it an integral part of professional practice for all? PMID- 1642994 TI - A healthy skin [continuing nursing education]. AB - Nurses, midwives and health visitors often care for patients/clients with skin problems, so it is important they have the relevant knowledge and skills to deliver quality care in this sensitive area of practice. PMID- 1642995 TI - HIV/AIDS: approaching saturation point. PMID- 1642996 TI - Waving the flag for care. Interview by Alex Mathieson. PMID- 1642997 TI - Whistleblowing: whistling in the dark? PMID- 1642998 TI - Health screening for elderly people. PMID- 1642999 TI - Role and function of professional nursing. PMID- 1643000 TI - Malignant melanoma and sun exposure. AB - The awareness of 160 subjects about the dangers of over-exposure to the sun in relation to development of malignant melanoma was surveyed using a questionnaire. The survey found that despite wide acknowledgement of the dangers of ultraviolet radiation to the skin, the desire to get a suntan was still very strong and insufficient protection was being used. Advice continued to be required on all aspects of sun protection and on the importance of regularly examining the skin for changes in moles, a health education activity in which nurses have the skills to become fully involved. PMID- 1643001 TI - Perceptions of team midwifery. AB - This small study was conducted in a maternity unit which had implemented team midwifery one year previously. A period of non-participant observation of activities on a labour ward over ten shifts was followed by nine semi-structured interviews with midwives of various grades. While the initial aim of the study was to investigate the interpersonal aspects of collegial activity among midwives, the respondents gave many valuable comments on team midwifery. The general view was that team midwifery allowed them greater opportunities to develop a rapport with mothers and also provided more chances for personal and career development. PMID- 1643002 TI - Using peer audit in health visiting. AB - South Tees Health Authority is one of 12 pilot sites for quality assurance. Most staff in the community and mental health unit are involved with the setting of professional standards. This article describes health visitors' experience of peer audit, carried out on one of the standards set within their quality assurance standard setting group. The nine health visitors attached to general practices serving Redcar and the surrounding district set professional standards based on Donabedian's structure, process and outcome model. Standards were set in areas such as communication, immunisation, health promotion, and child health clinics. PMID- 1643003 TI - A hectic morning in a psychiatric nurse's life. PMID- 1643004 TI - Information technology: tomorrow's skills today. PMID- 1643005 TI - Tradimus. Student networks work. PMID- 1643006 TI - Tradimus. Student power: in search of a wise council. PMID- 1643007 TI - Tradimus. Project 2000: look back in danger. PMID- 1643009 TI - Tradimus. Student empowerment: double dealing with the media. PMID- 1643008 TI - Tradimus. Equal opportunities: defining equality. PMID- 1643010 TI - Tradimus. Placements: accent on emergencies. PMID- 1643011 TI - Tradimus. Ward placements: primary school. PMID- 1643012 TI - Cellular sites of extrarenal and renal erythropoietin production in anaemic rats. AB - The cellular origins of erythropoietin were investigated in the rat using a probe derived from a cloned rat erythropoietin cDNA. In anaemic-hypoxic rat liver, in situ hybridization detected erythropoietin mRNA primarily in hepatocytes and less frequently in nonparenchymal sinusoidal or perisinusoidal liver cells. An RNase protection assay was used to compare the erythropoietin mRNA contents of separated rat liver cell fractions and also suggested that hepatocytes are the major source of extrarenal erythropoietin with nonparenchymal liver cells contributing less than 1% to total hepatic erythropoietin production. In kidney, in situ hybridization localized erythropoietin mRNA in nonepithelial cells, as yet of undefined lineage, in the cortical and outer medullary interstitium. These results indicate that, in the rat, the primary sources of erythropoietin in liver and kidney are different types of cells. PMID- 1643013 TI - Interferon-alpha therapy during pregnancy in chronic myelogenous leukaemia and hairy cell leukaemia. AB - Interferon-alpha is an effective agent in the treatment of chronic myelogenous leukaemia and hairy cell leukaemia. Because interferon-alpha does not inhibit DNA synthesis, we have used it to treat these diseases during pregnancy. We report here two patients with chronic myelogenous leukaemia and two patients with hairy cell leukaemia managed with interferon-alpha during pregnancy. Interferon-alpha was well tolerated, and the pregnancies proceeded without complications. All four infants were apparently normal at birth, and all four have enjoyed normal growth and development. Interferon-alpha may represent relatively safe therapy during pregnancy, because of its lack of inhibition of DNA synthesis. Nevertheless, recommendations regarding the use of interferon-alpha to treat chronic leukaemias during pregnancy must await further experience with this agent in this setting. PMID- 1643014 TI - A randomized study of intermediate versus conventional-dose cytarabine as intensive induction for acute myelogenous leukaemia. AB - The optimal dose of cytarabine for induction chemotherapy is unknown. Most studies have utilized doses of 100-200 mg/m2/d, although higher doses have been proposed to increase the concentration of the active metabolite ara-CTP within leukaemia cells. To address this question 101 adults with newly diagnosed acute myeloid leukaemia were randomized to receive treatment with daunorubicin and either conventional-dose cytarabine (200 mg/m2/d by continuous infusion) or an intermediate-dose of cytarabine (500 mg/m2 every 12 h). 36/51 (71%) patients assigned to conventional-dose cytarabine achieved complete remission compared to 37/50 (74%) who achieved remission with intermediate-dose cytarabine (P = 0.9). Patient age significantly affected remission rate. 8/17 patients age greater than 60 assigned to conventional-dose cytarabine and 10/17 assigned to intermediate dose cytarabine achieved complete remission compared to 27/33 patients under age 60 assigned to the conventional dose and 28/34 patients assigned to the intermediate dose arm (P = 0.004). Actuarial 4-year disease-free survival for patients assigned to conventional-dose cytarabine was 20 +/- 16% versus 28 +/- 17% for patients assigned to intermediate-dose cytarabine (P = 0.9). We conclude that intermediate dose cytarabine did not substantially improve results of induction chemotherapy for acute myeloid leukaemia. PMID- 1643015 TI - The immunophenotype in infant acute lymphoblastic leukaemia: correlation with clinical outcome. An Italian multicentre study (AIEOP). AB - A detailed analysis of immunophenotype of 112 infants aged less than 18 months with acute lymphoblastic leukaemia (ALL) was performed. Patients were divided into three groups on the basis of age at presentation (under 6 months: group 1: 6 12 months: group 2; 13-18 months: group 3). There were three cases of T-ALL (2.6%). The proportion of other subtypes was: common ALL in 59 patients (52.68%), pre-B ALL in 15 patients (13.3%), pre-pre-B ALL in 27 (24.1%) and acute undifferentiated leukaemia (AUL) in eight patients (7.14%). In non-T ALL, positivity to CD10 (corresponding to C-ALL and pre-B ALL) was distributed in the three age groups as follows: 38.88% (group I) 65.38% (group II) and 86.36% (group III). Conversely, immature phenotypes (pre-pre-B and AUL) were found more often in the younger patients of groups I and II, as well as anomalous phenotypes, such as the presence of myeloid antigens (MyAg) and of CD7. Prognostic significance was evaluated as event-free survival (EFS) by statistical analysis. A better outcome in CD10-positive ALL than in CD10-negative ones (48% v. 25% of long-term survivors) was demonstrated in all infants. Similarly, EFS was significantly better in MyAg-negative than in MyAg-positive cases. These results were confirmed also when adjusting for white blood cell count. This allowed the identification of CD10-negative, MyAg-positive ALL, which were relatively more frequent in infants and had a poorer clinical outcome with the current therapies. This study stresses the prognostic relevance of the immunological study in infant leukaemias and its utility in choosing different therapeutic modalities for poor risk phenotypes. PMID- 1643016 TI - Non-radioactive in situ hybridization for the detection and monitoring of trisomy 12 in B-cell chronic lymphocytic leukaemia. AB - Non-radioactive in situ hybridization (NISH) with a chromosome 12-specific alpha satellite probe was performed on 20 patients with chronic lymphocytic leukaemia (CLL) with normal karyotype (15 cases) or with inadequate mitotic yield (5 cases) from mitogen-stimulated cultures. All patients had over 70% lymphocytes coexpressing the CD5/CD23 antigens. While less than 1% interphase nuclei showed three fluorescent spots in 16/20 patients, evidence of trisomy 12 in 15-25% interphase cells was detected in four patients. According to the FAB classification the diagnosis in these patients was typical B-CLL, stage III (Rai's staging system) in one case, CLL/PLL, stage II and III in two cases, PLL, stage III in one case. In order to confirm these results, NISH was repeated after 1 month in one patient and after 2 years in three patients. All patients had been treated with chemotherapy in the period between the two NISH experiments. In all cases a 1.8-3-fold increase of percentage of trisomic interphase cells was detected. These findings suggest that in B-CLL clones with trisomy 12 may have proliferative advantage over clonal B-lymphocyte without +12 and, possibly, that they may be more resistant to chemotherapy. We conclude that NISH is a sensitive technique allowing for the detection and monitoring of trisomy 12 in a fraction of B-CLL patients with normal karyotype or with no analysable mitoses despite employment of polyclonal B-cell mitogens. PMID- 1643017 TI - Mini-BEAM followed by BEAM and ABMT for very poor risk Hodgkin's disease. AB - High dose chemotherapy and autologous bone marrow transplantation (ABMT) is an effective form of salvage therapy in patients with relapsed or resistant Hodgkin's disease. Patients with large tumour masses at the time of ABMT have a poorer prognosis and we have therefore administered intermediate dose BCNU, etoposide, cytarabine and melphalan (mini-BEAM) prior to high dose therapy with the same agents (BEAM) and ABMT in such patients. In addition we have used the same strategy in patients with bone marrow infiltration at the time of relapse in an attempt to clear the bone marrow for transplant. A total of 23 patients received mini-BEAM and 21 proceeded to BEAM and ABMT. Platelet engraftment was delayed compared to BEAM recipients who had not received mini-BEAM (P = 0.008) but there was only one procedure related death. Responses to BEAM and ABMT were not predicted by the response to mini-BEAM indicating a dose response effect at the upper end of the dose intensity spectrum. At 2 years, the overall survival and progression free survival are 61% and 46% respectively for this group of Hodgkin's patients with extremely poor prognosis. PMID- 1643018 TI - Chromosome 11q rearrangements in B non Hodgkin's lymphoma. AB - The clinical features, morphology and immunophenotype of 20 cases of B non Hodgkin's lymphoma (B-NHL) with chromosome abnormalities involving 11q13-14 were studied, to determine if this abnormality was closely associated with a specific sub-type of B-NHL. A t(11;14)(q13;q32) was found in 11 cases of intermediately differentiated lymphocytic lymphoma (IDLL). A breakpoint in the major translocation cluster of the BCL-1 locus was found in six of these cases. These patients were male with lymphomatous involvement of the bone marrow, marked splenomegaly and frequently had mucosa associated lymphoid tissue involvement. One patient with IDLL had a t(8;11)(p21;q13) and a rearranged BCL-1 locus, suggesting that this may be a variant of t(11;14)(q13;q32). Diagnoses of IDLL, chronic lymphocytic leukaemia, lymphoplasmacytic lymphoma and monocytoid B cell lymphoma were made in all but one of the remaining cases. These cases had either a translocation involving 11q13-14 and various partner chromosomes or an 11q13 deletion. This study demonstrates that 11q abnormalities occur mainly in a group of low-grade B-NHL of non follicle centre cell lineage. PMID- 1643019 TI - Measurement of free kappa and lambda chains in serum and the significance of their ratio in patients with multiple myeloma. AB - An inhibition enzyme-linked immunoassay technique using commercially available antibodies has been developed for the quantitation of both kappa and lambda light chains in the serum of patients with B-cell malignancies. Assay conditions were selected to enable measurement of free light chains in the concentration range between 0.1 and 20 mg/l. The normal range for free lambda chains in serum was found to be 0.4-4.2 mg/l and for free kappa chains it was 1.6-15.2 mg/l. At diagnosis the serum of most patients with multiple myeloma contained increased levels of the malignant free light chain and in some cases there was also elevation of the non-malignant light chain. The absolute level of the malignant light chain at diagnosis did not correlate with survival nor with laboratory parameters such as IgM or creatinine. A correlation with beta 2 M and serum paraprotein levels was evident only in cases of IgA myeloma. Although the absolute level of free serum light chain had no value as a prognostic indicator, the ratio of kappa:lambda chains closely followed the clinical assessment of disease status, being near the normal range (1.2-9.1) in plateau phase or stable disease. During periods of progressive disease this ratio ranged from 19 to 460 (n = 14) in patients with kappa myeloma, and 0.0013-0.14 (n = 9) in patients with lambda myeloma. Determination of the ratio of free light chains in the serum may allow effective monitoring and earlier warning of disease progression in patients with multiple myeloma. PMID- 1643020 TI - Mutations of the p53 tumour suppressor gene in haematologic neoplasms. AB - Mutations of the p53 tumour suppressor gene have frequently been observed in several types of solid tumours and are believed to be implicated in the development of these tumours. To determine the relevance of p53 mutations in haematologic neoplasms, we performed polymerase chain reaction-single strand conformation polymorphism analysis on the p53 gene in 45 patients with various types of haematologic neoplasms. In exons 5-8 containing highly conserved regions, mobility shifts indicating sequence alterations were detected in four of the 45 patients, and subsequent sequencing was performed. A point mutation resulting in a novel stop codon was detected at codon 213 in one of 23 cases of chronic myelogenous leukaemia (one of five cases of blast crisis). Point mutations causing amino acid substitutions were detected in one of four cases of myelodysplastic syndrome at codon 195, one of three cases of adult T-cell leukaemia at codon 281, and one of eight cases of acute lymphoblastic leukaemia at codon 281, and these missense mutations were accompanied by loss of the wild type allele. Patients harbouring these nonsense and missense mutations were in advanced disease stages. These findings suggest that mutational inactivation of the p53 gene is infrequent but is involved in the tumorigenesis of several types of haematologic neoplasms at least in some cases. PMID- 1643021 TI - Studies on macromolecular activators of phagocytosis from platelets (MAPPs) using anti MAPP murine monoclonal antibodies. AB - 1-MAPP(290 kD) and s-MAPP(150 kD) are glycoproteins which have been shown to be involved in released products from platelets (PRPr) and to activate monocyte and neutrophil phagocytosis via the Fc receptors. Three IgG 2a (kappa) murine monoclonal antibodies against 1-MAPP and nine IgG1 (kappa) antibodies against s MAPP have been raised. By affinity chromatography using these monoclonal antibodies, active MAPPs were obtained from the supernatant of outdated platelet concentrates in the presence of 60% saturated ammonium sulphate and from PRPr rich medium, and substantial amounts of non-functioning immunoreactive MAPPs were obtained from the precipitate. Fab fragments of one of the two anti 1-MAPP and of two of the four anti s-MAPP monoclonal antibodies inhibited the function of their corresponding MAPPs, but none of them could inhibit the other MAPPs. 1-MAPP and s MAPP in the platelets were visualized by indirect fluorescent antibody technique using Fab fragments of the antibodies. PMID- 1643022 TI - The relationship between increased platelet count and megakaryocyte size in bronchial carcinoma. AB - This study investigates megakaryocyte size in bronchial carcinoma and its relationship to platelet count, mean platelet volume and platelet function, the latter determined in vivo by measurement of the cutaneous bleeding time. Measurements were performed in 19 patients with bronchial carcinoma and 11 patients with a hiatus hernia (controls). Platelet count (335 +/- 123 v. 241 +/- 72 x 10(9)/l) and megakaryocyte total area (772 +/- 135 v. 666 +/- 105 microns 2) (mean +/- standard deviation) were both significantly increased in patients with bronchial carcinoma when compared to controls whilst the bleeding time was shorter in the patient group (253 +/- 116 v. 321 +/- 80 s). Patients with bronchial carcinoma were older (60.2 +/- 8.4 v. 48.8 +/- 13.2 years) and smoked more heavily (760 +/- 511 v. 92 +/- 175 cigarette years) than controls. Megakaryocyte size, platelet count and bleeding time all correlated with smoking habit (r = 0.395, P = 0.031; r = 0.622, P less than 0.001; r = 0.515, P = 0.004 respectively). There were no statistically significant differences between the groups with respect to gender or mean platelet volume. When considering all patients, significant correlations existed between platelet count and megakaryocyte area (r = 0.400, P = 0.029), and bleeding time and megakaryocyte area (r = -0.365, P = 0.047). The megakaryocyte nuclear and cytoplasmic areas were positively correlated (r = 0.855, P less than 0.001). This study suggests that the elevated platelet count in patients with bronchial carcinoma is mediated by an increase in the size of bone marrow megakaryocytes although the results are compounded by the association between smoking and megakaryocyte/platelet parameters. PMID- 1643023 TI - Electrophoretic and functional characteristics of the von Willebrand factor in human fetal plasma. AB - Although the haemostatic role of von Willebrand factor (vWF) in adults is well known, there is little information currently available about its possible contribution to in utero haemostasis. We have investigated the distribution of vWF multimers in 27 pure fetal platelet-poor plasma (FP) samples aged from 20 to greater than 36 weeks, by using electrophoresis in both low- and high-resolution agarose gels in the presence of sodium dodecyl sulphate. Our data confirm that most FP samples contain higher molecular weight (HMW) vWF multimers than those present in normal adult plasma, the proportion of these HMW forms being lower in FP samples aged greater than 36 weeks. However, we found that the multimeric unit and the protomeric form of vWF were similar in normal fetal and adult plasma. Functional assays of vWF were performed on three pooled FP samples. In all cases, fetal vWF was able to interact with factor VIII and to bind to GP Ib platelet receptor in the presence of ristocetin and to types I and III collagen. These results indicate that plasma vWF has already acquired in fetal life the functional activities required for its role in both coagulation and primary haemostasis. PMID- 1643024 TI - Factor VIII gene deletions in haemophilia A patients in Czechoslovakia. AB - Genomic DNA from 90 Czechoslovak haemophilia A patients from 81 pedigrees was analysed by Southern blotting and hybridization with factor VIII cDNA probes. Three partial deletions of the factor VIII gene were identified and characterized: a 4.8 kilobase (kb) deletion eliminating exon 10 in one patient with severe haemophilia A without inhibitor, a 6.1 kb deletion eliminating the 3' part of intron 13 and the 5' part of exon 14 in two related severe haemophiliacs, but only one of them produced inhibitor, and a 4.6 kb deletion eliminating the 3' part of intron 13 and the 5' part of exon 14 in a severe haemophiliac with high titre inhibitor. Besides these three deletions, three different restriction site variants without apparent loss of DNA sequence were found. PMID- 1643025 TI - Rapid detection of a protein C gene mutation present in the asymptomatic and not in the thrombosis-prone lineage. AB - The presence of mutations in the serine protease domain of protein C was investigated by temperature gradient gel electrophoresis of PCR products in five patients with protein C deficiency and thrombosis. Molecules with an altered melting behaviour were detected in one subject with a history of venous and arterial thrombosis. Direct sequencing showed that a G deletion, present in the heterozygous state, caused a reading frame shift at Trp 300 and subsequently a premature termination at the codon 335. The resulting suppression of the protein C catalytic function explains the reduction of protease activity to half. In addition the mutation caused a reduction of the antigen level in plasma. Temperature gradient gel electrophoresis enabled the rapid detection of the gene alteration in the family of the propositus. Several members of the paternal lineage had had severe thrombotic episodes. Unexpectedly the mutation was found to be inherited from the clinically asymptomatic maternal lineage, thus suggesting that an additional unknown defect from the paternal lineage is present in the thrombosis-prone propositus. PMID- 1643026 TI - A beta-thalassaemia phenotype not linked to the beta-globin cluster in an Italian family. AB - This paper describes a family of Central Italian origin in which three patients in two generations had either thalassaemia intermedia or a late presenting form of thalassaemia major. Sequence analysis of the patients' DNA revealed that only one of the beta-globin genes was affected by a beta-thalassaemia mutation (the codon 39 nonsense mutation), the other being completely normal, apart from the complex rearrangement (-T +ATA) at position -530 5' to the CAP site of the beta globin gene, which has uncertain clinical significance. Haematologically, all these patients were characterized by unusually low HbF levels (1.8-7.3%) for a beta-thalassaemia major or intermedia phenotype. The mother of the two patients with thalassaemia intermedia was heterozygous for beta-thalassaemia (codon 39 nonsense mutation), while the father had thalassaemia-like red cell indices, an increased alpha/non alpha chain synthesis ratio, a slight increase of HbF and a low HbA2 level, but showed entirely normal beta-globin gene sequences, apart from the complex rearrangement (-T +ATA) at position -530 5' to the CAP site. One of the thalassaemia intermedia patients married a normal woman and they had a child with thalassaemia major who inherited only the codon 39 nonsense mutation but not the complex rearrangement at position -530. The clinical phenotype of thalassaemia-intermedia or major in the patients from this family may be explained by postulating the inheritance of the double heterozygous state for beta-thalassaemia and for a mutation in a gene coding for an erythroid-specific DNA binding protein which may impair the function of the normal beta-globin gene. Heterozygosity for this postulated mutation (father of the patients with thalassaemia intermedia) may result in the production of a beta-thalassaemia carrier state with normal HbA2 level. PMID- 1643027 TI - The effect of macrophage colony-stimulating factor on haemopoietic recovery after autologous bone marrow transplantation. AB - Macrophage colony-stimulating factor (M-CSF) is active in the late stages of monocyte maturation, activates mature monocyte-macrophages and enhances their production of various other cytokines. We have examined the effects of a 21 d course of escalating doses of M-CSF purified from human urine (hM-CSF) on recovery following autologous bone marrow transplantation (ABMT) in 20 patients with malignant lymphomas. Four patients were treated at each dose level of 4, 8, 16, 32 and 64 x 10(6) U/m2/d and results compared to 46 concurrent controls. There was no significant difference in recovery to an absolute neutrophil count (ANC) of 0.5 x 10(9)/l (median 20 d in hM-CSF group versus 22 in controls) or in recovery of platelets to 50 x 10(9)/l (32 d versus 39 d, 0.05 less than P less than 0.1); hM-CSF patients received a median of 81 platelet units following ABMT (controls 112 units, P = NS). hM-CSF patients had a median of 5.5 d with fever greater than 37.5 degrees C (control 8, P = NS), received parenteral antibiotics for 14.5 d (control 17, P = NS) and had a 50% incidence of bacteraemia (control 48%). hM-CSF treated patients were discharged by a median of day 29 following transplantation (control 33, P less than 0.05). Platelet and neutrophil recovery correlated significantly with the number of marrow mononuclear cells (MNC) reinfused in the hM-CSF group (P = 0.05 and P = 0.014 respectively) but not in controls. Subgroup analysis showed that hM-CSF patients receiving greater than 2 x 10(8) MNC/kg body weight reached an ANC of 0.5 x 10(9)/l by a median of day 16.5 (control 18.5, NS), became platelet transfusion independent by day 17 (control 29, P less than 0.05) and reached a platelet count of 50 x 10(9)/l by day 21 (control 40, P less than 0.05). No significant toxicity attributable to hM CSF treatment was seen. These results suggest that hM-CSF accelerates platelet recovery following ABMT and that relatively large marrow innocula are required to see this effect. PMID- 1643028 TI - Trisomy 8 detection in granulomonocytic, erythrocytic and megakaryocytic lineages by chromosomal in situ suppression hybridization in a case of refractory anaemia with ringed sideroblasts complicating the course of paroxysmal nocturnal haemoglobinuria. AB - Paroxysmal nocturnal haemoglobinuria (PNH) was diagnosed in a 20-year-old male patient who suffered from anaemia since the age of 11. Eighteen years after diagnosis, PNH transformed into refractory anaemia with ringed sideroblasts (RARS). Trisomy 8 was observed in 27%, 45% and 53% of the bone marrow metaphase cells analysed in 1987, 1988 and 1990 respectively. In order to determine which bone marrow cell lineages were affected by trisomy 8 and at which stage of stem cell differentiation, MAC (Morphology, Antibody, Chromosomes) and CISS (Chromosomal In Situ Suppression) hybridization techniques were combined. The MAC technique enables karyotypic analysis of morphologically and immunologically classified mitotic cells. CISS hybridization makes it possible to detect individual chromosomes and chromosome aberrations using recombinant DNA libraries from sorted human chromosomes. Trisomy 8 was detected in granulomonocytic (50.6%), erythrocytic (67.2%) and megakaryocytic (one megakaryocyte with trisomy 8, one normal) lineages, providing evidence for the occurrence of trisomy 8 in early haematopoietic cell precursors, at the GEMM or pluripotent level. Cytogenetic and clinical data suggest that the sideroblastic clone originated from a mutation affecting a cell of the PNH clone, progressively replaced by the PNH/RARS clone, due to proliferative advantage. PMID- 1643029 TI - Trace levels of factor VIII in substrate plasma. PMID- 1643030 TI - t(8;9)(p11;q32) in atypical chronic myeloid leukaemia: a new cytogenetic clinicopathologic association? PMID- 1643031 TI - Autoimmune processes terminating 24 years later in Hodgkin's disease. PMID- 1643032 TI - Disappearance of spontaneous erythroid colonies in patients with myeloproliferative disorders treated by alpha-interferon. PMID- 1643033 TI - In vitro proteolysis of red cell membrane in hereditary spherocytosis. PMID- 1643034 TI - Bone marrow transplantation for dyskeratosis congenita. PMID- 1643035 TI - A comparative spectroscopic study of tryptophan probes engineered into high- and low-affinity domains of recombinant chicken troponin C. AB - The spectral properties of three tryptophan-substituted mutants of recombinant chicken troponin C are compared. Site-specific mutagenesis was used to introduce a tryptophan residue into the high-affinity (Ca2+/Mg2+) domain of troponin C at residue position 105, thereby creating the mutant phenylalanine-105 to tryptophan (F105W). The spectral properties of F105W and a double mutant, F29W/F105W, were compared with the mutant phenylalanine-29 to tryptophan (F29W). Since wild-type chicken troponin C does not naturally contain either tyrosine or tryptophan residues, the tryptophan substitutions behaved as site-specific reporters of metal ion binding and conformational change. The residues that occupy positions 29 and 105 are at homologous locations in low-affinity and high-affinity domains, preceding the first liganding residues of binding loops I and III, respectively. Mutant proteins were examined by a combination of absorbance and fluorescence methods. Calcium induced significant changes in the near-UV absorbance spectra, fluorescence emission spectra, and far-UV circular dichroism of all three mutant proteins. Magnesium induced significant changes in the spectral properties of only F105W and F29W/F105W proteins. Tryptophan substitutions allowed Ca(2+) specific and Ca(2+)/Mg(2+) sites to be titrated independently of one another. Results indicate that there is no interaction between the two binding domains under conditions where troponin C is isolated from the troponin complex. Magnesium-induced changes in the environment of the tryptophan reporter at position 105 were significantly different from those induced by calcium. This suggests that calcium and magnesium differ in their influence on the conformation of the high-affinity, Ca(2+)/Mg(2+) sites. PMID- 1643036 TI - Europium(III) luminescence and tyrosine to terbium(III) energy-transfer studies of invertebrate (octopus) calmodulin. AB - The effects of minor differences in the amino acid sequences between a vertebrate (bovine testes) and an invertebrate (octopus) calmodulin on metal ion binding were investigated via laser-induced Eu3+ and Tb3+ luminescence. Amino acid substitutions at residues which are coordinated to the metal ion do not produce any detectable changes in the 7F0----5D0 excitation spectrum of the Eu3+ ion bound to octopus calmodulin relative to bovine testes calmodulin; only minor differences in the excited-state lifetime values in D2O solution are observed. The dissociation constants for Eu3+ (1.0 +/- 0.2 microM) and Tb3+ (5 +/- 1 microM) from the weak lanthanide binding sites (III and IV, numbered from the amino terminus) of octopus calmodulin were measured using luminescence techniques. Both values agree well with those reported previously for bovine testes calmodulin [Mulqueen, P. M., Tingey, J. M., & Horrocks, W. D., Jr. (1985) Biochemistry 24, 6639-6645]. The measured dissociation constant of Eu3+ bound in the tight lanthanide binding sites (I and II) is 6 +/- 2 nM for octopus calmodulin and 12 +/- 2 nM for bovine testes calmodulin. The distances between sites I and II (12.4 +/- 0.5 A) and sites III and IV (11.7 +/- 0.8 A) were determined from Forster-type energy transfer in D2O solutions of octopus calmodulin containing bound Eu3+ donor and Nd3+ acceptor ions. Forster theory parameters for nonradiative energy transfer between Tyr138 and Tb3+ ions bound at sites III and IV of octopus calmodulin were comprehensively evaluated, including a dynamics simulation of the orientation factor kappa 2. This theory is found to account quantitatively for the observed energy-transfer efficiency as evaluated from the observed sensitized Tb3+ emission. PMID- 1643037 TI - Solution structure of the EcoRI DNA octamer containing 5-fluorouracil via restrained molecular dynamics using distance and torsion angle constraints extracted from NMR spectral simulations. AB - The self-complementary DNA octamer [d(GGAATUFCC)]2, containing the EcoRI recognition sequence with one of the thymines replaced by 5-fluorouracil (UF), was synthesized. Proton homonuclear two-dimensional nuclear Overhauser effect (2D NOE) and double-quantum-filtered correlation (2QF-COSY) spectra, as well as one dimensional spectra at different temperatures, were recorded for the octamer. Consequently, all proton resonances were assigned. The thermally induced transition from the duplex to single strands has been followed, demonstrating the stability of the duplex containing 5-fluorouracil. Simulations of the 2QF-COSY cross-peaks by means of the programs SPHINX and LINSHA were compared with experimental data, establishing scalar coupling constants for the sugar ring protons and hence sugar pucker parameters. The deoxyribose rings exhibit a dynamic equilibrium of N- and S-type conformers with 75-95% populations of the latter. Two programs used for complete relaxation matrix analysis 2D NOE spectra, CORMA and MARDIGRAS, were modified to account for the influence of the fluorines on dipolar interactions in the proton system. Quantitative assessment of the 2D NOE cross-peak intensities for different mixing times, in conjunction with the program MARDIGRAS, gave a set of interproton distances for each mixing time. The largest and smallest values of each of the interproton distances were chosen as the upper and lower bounds for each distance constraint. The distance bounds define the size of a flat-well potential function term, incorporated into the AMBER force field, which was employed for restrained molecular dynamics calculations. Torsion angle constraints in the form of a flat-well potential were also constructed from the analysis of the sugar pucker data. Several restrained molecular dynamics runs of 35 ps were performed, utilizing 284 experimental distance and torsion angle constraints and two different starting structures, energy-minimized A- and B-DNA. Convergence to similar structures with a root-mean square deviation of 1.2 A was achieved for the central hexamer of the octamer, starting from A- and B-DNA. The average structure from six different molecular dynamics runs was subjected to final restrained energy minimization. The resulting final structure was in good agreement with the structures derived from different molecular dynamics runs and showed a substantial improvement of the 2D NOE sixth-root residual index in comparison with classical and energy-minimized B DNA. A detailed analysis of the conformation of the final structure and comparison with structures of similar sequences, obtained by different methods, were performed. PMID- 1643038 TI - Comparison of the dynamical structures of lipoamide dehydrogenase and glutathione reductase by time-resolved polarized flavin fluorescence. AB - Time-resolved polarized fluorescence spectroscopy has been applied to the bound FAD in the structurally related flavoproteins lipoamide dehydrogenase from Azotobacter vinelandii (LipDH-AV) and glutathione reductase (GR) from human erythrocytes. The fluorescence parameters as obtained from the maximum entropy analysis differ considerably in both enzymes, reflecting the unique properties of the flavin microenvironment. Three conformational substates are revealed in LipDH AV and five in GR. Almost 90% of the population of GR molecules has a fluorescence lifetime in the order of 30 ps which originates from efficient exciplex formation with Tyr197. Equilibrium fluctuations between conformational substates are observed for LipDH-AV on a nanosecond time scale in the temperature range 277-313 K. Interconversion between conformational substates in GR is slow, indicating that large activation barriers exist between the states. In agreement with these results, a model is postulated which ascribes a role in catalysis to equilibrium fluctuations between conformational substates in GR and LipDH-AV. From time-resolved fluorescence anisotropy as a function of temperature, distinction can be made between flavin reorientational motion and interflavin energy transfer. In both proteins intersubunit energy transfer between the prosthetic groups is observed. Furthermore, it is revealed that only the flavin in glutathione reductase exhibits rapid restricted reorientational motion. Geometric information concerning the relative orientation and distance of the flavins can be extracted from the parameters describing the energy-transfer process. The obtained spatial arrangement of the flavins is in excellent agreement with crystallographic data. PMID- 1643039 TI - Molecular relaxation spectroscopy of flavin adenine dinucleotide in wild type and mutant lipoamide dehydrogenase from Azotobacter vinelandii. AB - The temperature dependence of the fluorescence emission spectra of flavin adenine dinucleotide bound to lipoamide dehydrogenase from Azotobacter vinelandii shows that the protein matrix in the vicinity of the prosthetic group is rigid on a nanosecond time scale in a medium of high viscosity (80% glycerol). The active site of a deletion mutant of this enzyme, which lacks 14 C-terminal amino acids, is converted from a solid-state environment (on the nanosecond time scale of fluorescence) into a state where efficient dipolar relaxation takes place at temperatures between 203 and 303 K. In aqueous solution, fast dipolar fluctuations are observed in both proteins. It is shown from fluorescence quenching of the flavin by iodide ions that the prosthetic groups of the mutant protein are partially iodide accessible in contrast to the wild type enzyme. A detailed analysis of the temperature dependence of spectral energies according to continuous relaxation models reveals two distinct relaxation processes in the deletion mutant, which were assigned to solvent and protein dipoles, respectively. From the long-wavelength shifts of the emission spectra upon red edge excitation, it is demonstrated that the active site of the wild type enzyme has high structural homogeneity in comparison to the deletion mutant. In combination with results obtained by X-ray diffraction studies on crystals of the wild type enzyme, it can be concluded that the C-terminal polypeptide of the A. vinelandii enzyme interacts with the dehydrolipoamide binding site, thereby shielding the flavins from the solvent. PMID- 1643040 TI - 19F-NMR spin-spin relaxation (T2) method for characterizing volatile anesthetic binding to proteins. Analysis of isoflurane binding to serum albumin. AB - This paper characterizes the low-affinity ligand binding interactions of a fluorinated volatile anesthetic, isoflurane (CHF2OCHClCF3), with bovine serum albumin (BSA) using 19F-NMR transverse relaxation (T2). 19F-NMR spectra of isoflurane in aqueous BSA reveal a single isoflurane trifluoromethyl resonance, indicative of rapid exchange of isoflurane between protein-bound and aqueous (free) environments. The exchange is slow enough, however, that the chemical shift difference between bound and free isoflurane (delta omega = 0.545 ppm) contributes to the observed isoflurane T2. The contribution of delta omega to T2 can be minimized by shortening the interval between 180 degrees refocusing pulses in the Carr-Purcell-Meiboom-Gill pulse sequence used to monitor T2. Analysis of the dependence of T2 on interpulse interval additionally allows determination of the T2 (6.2 ms) and the average lifetime (tau b = 187 microseconds) of bound isoflurane molecules. By use of a short interpulse interval (less than 100 microseconds), T2 measurements can readily be used to analyze equilibrium binding of isoflurane to BSA. This analysis revealed a discrete saturable binding component with a KD = 1.4 mM that was eliminated either by coincubation with oleic acid (6 mol/mol of BSA) or by conversion of BSA to its "expanded" form by titration to pH 2.5. The binding was independently characterized using a gas chromatographic partition analysis (KD = 1.4 mM, Bmax = 3-4 sites). In summary, this paper describes a method whereby T2 measurements can be used to characterize equilibrium binding of low-affinity ligands to proteins without the confounding contributions of chemical shift.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1643041 TI - Role of proline residues in human lysozyme stability: a scanning calorimetric study combined with X-ray structure analysis of proline mutants. AB - It has been shown that protein stability can be modulated from site-directed mutations that affect the entropy of protein unfolding [Matthews, B. W., Nicholson, H., & Becktel, W. J. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 6663 6667]. However, the effect of a specific amino acid replacement on stability highly depends on the location of the mutation site and its environment in the protein structure [Yutani, K., Hayashi, S., Sugisaki, Y., & Ogasahara, K. (1991) Proteins Struct., Funct., Genet. 9, 90-98). To clarify the role of specific proline residues in the thermostability of human lysozyme (h-lysozyme), a series of proline mutants were investigated by means of scanning calorimetry and high resolution X-ray crystallography. The thermodynamic properties of the mutant and wild-type h-lysozymes are compared and discussed on the basis of their three dimensional structure. h-Lysozyme contains two proline residues at positions 71 and 103. The Pro71----Gly substitution was found to destabilize h-lysozyme by decreasing the entropic contribution of unfolding by about 2 kcal/mol at 68.8 degrees C. This is consistent with the theoretical expectations for such a substitution. However, the same substitution at position 103 (Pro103----Gly) does not affect h-lysozyme stability, and the thermodynamic properties of the P71G/P103G and P71G mutants are essentially the same. Pro71 which is conserved among lysozymes from other species, appears to be important for stability, whereas Pro103, which is not conserved, does not. These differences are explained in terms of residue accessibility to the solvent and crystallographic B-factor, which reflects the amino acid mobility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1643042 TI - Role of the B-ring substituent in the fluorescence of colchicinoid-tubulin and allocolchicinoid-tubulin complexes. AB - Fluorescence spectra of several B-ring derivatives of allocolchicine in a variety of solvents have been obtained. The quantum yields of the allocolchicine derivatives decreased with amine substitution at the C-7 position [R = H greater than NH2 much greater than NHCH3 greater than N(CH3)2]. The relative fluorescent intensities of the aminoallocolchicinoids [R = NH2, NHCH3, N(CH3)2] bound to tubulin were significantly less than the fluorescent intensities of tubulin-bound allocolchicine (R = NHCOCH3) and deacetamidoallocolchicine (R = H). The low fluorescent intensities of the aminoallocolchicinoids in solvents and bound to tubulin could be explained by exciplex formation between the lone pair of electrons on the nitrogen and the allocolchicinoid pi-system, which leads to quenching of the allocolchicinoid fluorescence. Direct evidence for exciplex formation between the C-7 amine nitrogen and the allocolchicinoid pi-system was found in the emission spectrum of N-methyldemeallocolchicine [R = N(CH3)2] in dioxane. The quantum yields of the aminoallocolchicinoids in glycerol were higher than would be predicted on the basis of solvent dielectric effects. Glycerol appears to increase the quantum yields of the aminoallocolchicinoids through both viscosity and hydrogen-bonding effects. The latter effect serves to sequester the lone pair of electrons on the nitrogen, decreasing its ability to interact with the pi-system of the allocolchicinoid. It is concluded that the fluorescent properties of colchicinoids and allocolchicinoids in glycerol are not reliable indicators of the fluorescent properties of the molecules bound to tubulin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1643043 TI - NMR structural characterization of the reaction product between d(GpG) and the octahedral antitumor complex trans-RuCl2(DMSO)4. AB - The reaction between the antitumor octahedral complex trans-RuCl2(DMSO)4 and d(GpG) leads to the formation of a stable compound characterized by a covalent bifunctional coordination of the bases to the metal center. The structure of the compound has been fully characterized by NMR and molecular modeling studies, showing the presence of two N7-coordinated guanine moieties in a head to head conformation, two dimethyl sulfoxide molecules, and one halogen atom in the coordination sphere of the ruthenium. The glycosidic chi angles are essentially in the anti range, the sugar puckering of the 5'G is 3'-endo (100% N), whereas that of the 3'G is more flexible but mainly in 2'-endo conformation (85% S), the two bases are strongly destacked. The compound shows structural features which are surprisingly similar to those exhibited by the corresponding cisplatin complex, indicating that such a way of interaction with DNA is not exclusive to Pt or to metals with square planar coordination geometries. PMID- 1643044 TI - Crystal structure of a pentamidine-oligonucleotide complex: implications for DNA binding properties. AB - The crystal structure of the complex formed between the dodecanucleotide d(CGCGAATTCGCG)2 and the drug pentamidine, which is active against the Pneumocystis carinii pathogen in AIDS patients, has been determined to a resolution of 2.1 A and an R-factor of 19.4%. Analysis of the structure has shown the drug to be bound in the 5'-AATT minor groove region of the duplex, with the amidinium groups H-bonded to adenine N3 atoms in an interstrand manner. The drug molecule adopts an extended conformation, and the immediate binding site spans four base pairs. Structural details of the drug-DNA interactions are discussed, and comparison is made with the dodecamer complex of the structurally similar berenil ligand. PMID- 1643045 TI - DNA packaging induced by micellar aggregates: a novel in vitro DNA condensation system. AB - Evidence for a conceptually novel DNA packaging process is presented. X-ray scattering, electron microscopy, and circular dichroism measurements indicate that in the presence of positively charged micellar aggregates and flexible anionic polymers, such as negatively charged polypeptides or single-stranded RNA species, a complex is formed in which DNA molecules are partially embedded within a micellar scaffold and partially condensed into highly packed chiral structures. Based on studies of micelle-DNA and micelle-flexible anionic polymer systems, as well as on the known effects of a high charge density upon the micellar organization, a DNA packaging model is proposed. According to this model, the DNA induces the elongation of the micelles into rodlike aggregates, forming a closely packed matrix in which the DNA molecules are immobilized. In contrast, the flexible anionic polymers stabilize clusters of spherical micelles which are proposed to effect a capping of the rodlike micelles, thus arresting their elongation and creating surfactant-free segments of the DNA that are able to converge and collapse. Thus, unlike other in vitro DNA packaging systems, in which condensation follows encounters between charge-neutralized DNA molecules, a prepackaging phase where the DNA is immobilized within a matrix is proposed in this case. Cellular and nuclear membranes have been implicated in DNA packaging processes in vivo, and negatively charged polyelectrolytes were shown to be involved in the processes. These observations, combined with the basic tenets of the DNA condensation system described here, allow for the progression to the study of more elaborate model systems and thus might lead to insights into the nature and roles of the intricate in vivo DNA-membrane complexes. PMID- 1643046 TI - The human colipase gene: isolation, chromosomal location, and tissue-specific expression. AB - The digestion of dietary triglycerides occurs in the duodenum through the action of triglyceride lipase, a pancreatic exocrine protein. The activity of pancreatic lipase is inhibited by the bile salts normally found in the gut lumen. Another pancreatic exocrine protein, colipase, restores the lipolytic activity of triglyceride lipase. The synthesis and secretion of both triglyceride lipase and colipase is increased by dietary fats and secretin. An increase in mRNA accompanies the increased activity, suggesting that the genes for triglyceride lipase and colipase contain nucleotide elements responsive to dietary fats or secretin or both. To study the regulation of colipase expression, we have first isolated the gene for human colipase from a cosmid library with a cDNA probe. The gene was localized to chromosome 6 and is organized into three exons contained in a single 3.3-kb BamHI fragment. The 5'-flanking region of the gene contains a TATA box, a GC box, and a 28-bp region with homology to the rat pancreatic specific enhancer. This region directs the tissue-specific expression of the chloramphenicol acetyltransferase gene in a transfected rat pancreatic acinar cell line, AR42-J. The same construct is inactive in HEPG2, C2C12, and COS-1 cells. These results demonstrate that the isolated gene for human colipase contains tissue-specific promoter activity in the 5'-flanking DNA. The 28-bp region specifically binds to a factor in nuclear extracts. PMID- 1643047 TI - Energy transduction during catalysis by Escherichia coli DNA photolyase. AB - Native DNA photolyase from Escherichia coli contains 1,5-dihydroFAD (FADH2) plus 5,10-methenyltetrahydropteroylpolyglutamate. Quantum yield and action spectral data for thymine dimer repair were obtained by using a novel multiple turnover approach under aerobic conditions. This method assumes that catalysis proceeds via a (rapid-equilibrium) ordered mechanism with light as the second substrate, as verified in steady state kinetic studies. The action spectrum observed with native enzyme matched its absorption spectrum and an action spectrum simulated based on an energy transfer mechanism where dimer repair is initiated either by direct excitation of FADH2 or by pterin excitation followed by singlet-singlet energy transfer to FADH2. The quantum yield observed for dimer repair with native enzyme (phi Native = 0.722 +/- 0.0414) is similar to that observed with enzyme containing only FADH2 (phi EFADH2 = 0.655 +/- 0.0256), as expected owing to the high efficiency of energy transfer from the natural pterin to FADH2 [EET = 0.92]. The quantum yield observed for dimer repair decreased (2.1-fold) when the natural pterin was partially (68.8%) replaced with 5,10-CH(+)-H4folate (phi obs = 0.342 +/- 0.0149). This is consistent with the energy transfer mechanism (phi calc = 0.411 +/- 0.0118) since a 2-fold lower energy transfer efficiency is observed when the natural pterin is replaced with 5,10-CH(+)-H4folate (EET = 0.46) (Lipman & Jorns, 1992). The action spectrum observed for 5,10-CH(+)-H4folate-supplemented enzyme matched a simulated action spectrum which exhibited a small (5 nm) hypsochromic shift as compared with the absorption spectrum (lambda max = 385 nm).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1643048 TI - Activity and spectroscopic properties of the Escherichia coli glutamate 1 semialdehyde aminotransferase and the putative active site mutant K265R. AB - Glutamate 1-semialdehyde aminotransferase (glutamate 1-semialdehyde 2,1 aminomutase; EC 5.4.3.8; GSA-AT) catalyzes the transfer of the amino group on carbon 2 of glutamate 1-semialdehyde (GSA) to the neighboring carbon 1 to form delta-aminolevulinic acid (ALA). To gain insight into the mechanism of this enzyme, possible intermediates were tested with purified enzyme and the reaction sequence was followed spectroscopically. While 4,5-dioxovaleric acid (DOVA) was efficiently converted to ALA by the pyridoxamine 5'-phosphate (PMP) form of the enzyme, 4,5-diaminovaleric acid (DAVA) was a substrate for the pyridoxal 5' phosphate (PLP) form of GSA-AT. Thus, both substances are reaction intermediates. The purified enzyme showed an absorption spectrum with a peak around 338 nm. Addition of PLP led to increased absorption at 338 nm and a new peak around 438 nm. Incubation of the purified enzyme with PMP resulted in an additional absorption peak at 350 nm. The reaction of the PLP and PMP form of the enzyme with GSA allowed the detection of a series of peaks which varied in their intensities in a time-dependent manner. The most drastic changes to the spectrum that were observed during the reaction sequence were at 495 and 540 nm. Some of the detected absorption bands during GSA-AT catalysis were previously described for several other aminotransferases, indicating the relationship of the mechanisms. The reaction of the PMP form of the enzyme with DOVA resulted in a similar spectrum as described above, while the spectrum for the conversion of DAVA by the PLP form of the enzyme indicated a different mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1643049 TI - A proteolytically sensitive region common to several rat liver cytochromes P450: effect of cleavage on substrate binding. AB - Limited proteolysis of rat liver microsomes was used to probe the topography and structure of cytochrome P450 bound to the endoplasmic reticulum. Three cytochromes P450 from two families were examined. Monoclonal antibodies to cytochrome P450 forms 1A1, 2B1, and 2E1 were used to immunopurify these proteolyzed cytochromes P450 from microsomes from rats treated with 3 methylcholanthrene, phenobarbital, and acetone, respectively. Electrophoretic and immunoblot analysis of tryptic fragments revealed a highly sensitive cleavage site in all three cytochromes P450. N-Terminal sequencing was performed on the fragments after transfer onto poly(vinylidene difluoride) membranes and showed that this preferential cleavage site is at amino acid position 298 of P450 1A1, position 277 of P450 2B1, and position 278 of P450 2E1. Multiple sequence alignment revealed that these positions are at the amino terminal of a highly conserved region of these cytochromes P450. The important functional role implied by primary sequence conservation along with the proteolytic sensitivity at its amino terminal suggests that this region is a protein domain. Comparison with the known structure of the bacterial cytochrome P450cam predicts that this proteolytically sensitive site is within an interhelical turn region connected to the distal helix that partially encompasses the heme-containing active site. Substrate binding to the cleaved cytochromes P450 was examined in order to determine whether the newly added conformational freedom near the cleavage site functionally altered these cytochromes P450. Cleavage of P450 2B1 abolished benzphetamine binding, which indicates that the cleavage site contains an important structural determinant for binding this substrate. However, cleavage did not affect benzo[a]pyrene binding to P450 1A1. PMID- 1643050 TI - Identification of the sterol- and actin-binding domains of plasma vitamin D binding protein (Gc-globulin). AB - The mammalian plasma vitamin D binding protein (DBP), or Gc-globulin, is recognized to have at least two functional properties: sterol binding and G-actin sequestration. Affinity labeling of the sterol binding site with the radioactive electrophilic ligand, 3 beta-(bromoacetoxy)-25-hydroxycholecalciferol, followed by limited proteolysis, permitted the isolation and identification of three overlapping peptides in the amino terminus of the molecule. When G-actin affinity chromatography was applied to other proteolytic fragments, two fragments from the carboxy terminus of the molecule were isolated and identified. Another, large, tryptic fragment displayed both sterol- and actin-binding properties. The amino terminal assignment of the sterol-binding domain was confirmed by demonstrating sterol-specific binding by an in vitro transcribed and translated product of a mutated rat DBP cDNA encoding a protein truncated in its carboxy terminus. The sterol-binding domain was localized to the region between the first-amino terminal disulfide bond, and the actin-binding domain was found between residues 350 and 403. A high degree of sequence conservation in these regions was found among human, rat, and mouse DBP's. These functional domain assignments confirm the apparent independence of these two binding activities and help to explain the observed triprotein complex of DBP-actin-DNase I and the competition between DBP and profilin for G-actin binding. Our findings should facilitate more precise delineation of the binding domains by site-directed mutagenesis experiments. PMID- 1643051 TI - Lateral diffusion and percolation in two-phase, two-component lipid bilayers. Topology of the solid-phase domains in-plane and across the lipid bilayer. AB - Fluorescence recovery after photobleaching (FRAP) has recently been used to examine the percolation properties of coexisting phases in two-component, two phase phosphatidylcholine bilayers [Vaz, W. L. C., Melo, E. C. C., & Thompson, T. E. (1989) Biophys. J. 56, 869-876]. We now report the use of FRAP to study two additional problems in similar systems. The first is the effect of solid-phase obstacles on the lateral diffusion in the fluid phase. The second is the question of whether or not, in a single bilayer, solid-phase domains in one monolayer are exactly superimposed on solid domains in the apposing monolayer. To address the first problem, the lateral diffusion of N-(7-nitrobenzoxa-2,3-diazol-4-yl)-1 palmitoyl-2-oleoylphosp hatidylethanolamine (NBD-POPE), a probe soluble only in the fluid phase when solid and fluid phases coexist, has been studied in the mixture N-lignoceroyldihydrogalactosylceramide (LigGalCer)/dipalmitoylphosphatidylcholine (DPPC). Percolation of the fluid phase occurs at a high mass fraction of solid phase. This indicates that the solid domains have a centrosymmetric shape, a characteristic which makes this a good experimental system to test theoretical simulations of diffusion in an archipelago. It is shown that agreement between theory and experiment is poor, a result that had already been observed when the obstacles were integral membrane proteins. We develop an effective-medium model for diffusion in two-phase systems which explains both our results and those obtained with integral proteins. The distinctive feature of the model is the consideration of an annular region around the obstacles where the lipids are more ordered than in the bulk fluid phase. The diffusion coefficient is then calculated by extending the free area model to two phase systems, taking these annuli into account. The second question, the organization of the solid-phase domains across the lipid bilayer, is examined in the systems LigGalCer/DPPC and dimyristoylphosphatidylcholine (DMPC)/distearoylphosphatidylcholine (DSPC) by comparing the diffusion of a fluid phase-soluble, gel-phase-insoluble lipid derivative which spans the two monolayers of a bilayer (NBD-membrane-spanning-phosphatidylethanolamine, NBD msPE) with that of a probe which is restricted to a single monolayer. In LigGalCer/DPPC, 20:80, the distribution of solid domains in one of the monolayers is independent of the distribution in the apposing monolayer. In contrast, in DMPC/DSPC, 50:50, the solid domains in one monolayer are exactly superimposed upon the solid domains existing in the apposing monolayer. PMID- 1643052 TI - Resolving conflict. PMID- 1643053 TI - The old 'doctor-nurse game'--today's professional nurses decide to quit playing. PMID- 1643054 TI - Illegal sexual harassment violations: are you a victim? PMID- 1643055 TI - Is the glass half full or half empty? PMID- 1643056 TI - Growth and development of regional units in the head and face based on anthropometric measurements. PMID- 1643057 TI - Anthropometric growth study of the head. AB - Five measurements of the head were taken between 1 year and 18 years of age in 1,537 North American Caucasians. By 1 year of age, the circumference (87.5%) and length (87.1%) of the head showed the highest levels of developmental level compared with their adult size. By 5 years, the developmental level of all measurements in head width, head length, and circumference increased, closely approaching maturation. Head length reached full maturation at 10 years in females (182.7 mm), and at 14 years in males (189.2 mm). In females, head width showed the most advanced maturation at 14 years (142.7 mm). In males, most of the head measurements matured at 15 years of age. Adult head height was approached at 13 years in both sexes (113.3 mm in males and 109.8 mm in females). Early rapid growth in head height and head length took place between 1 and 4 years of age, and between 1 and 6 years in forehead width. The head width and head circumference showed continuous but mild growth rates throughout this period. PMID- 1643058 TI - Growth patterns of the face: a morphometric study. AB - Age-related growth changes in the face and the relationships between its parts were calculated by using three vertical, two horizontal, and two projective surface measurements from 1,594 healthy North American Caucasians between 1 and 18 years of age. By 1 year, the width of the mandible was highly developed (80.2%) while its height reached only 66.6% of the eventual adult size. The mandible's height and width showed significant development between 1 and 5 years, while the face height, upper face height, face width, and the two face depth measurements exhibited continuous gradual growth after 5 years of age. In general, the face matured between 12 and 15 years in males and 2 years earlier in females. At 12 years, the upper face height, the mandible height, and the width of the face reached their mature size in females. At 15 years, the face height, mandible height, face width, and the depth of the mandible reached maturity in males. PMID- 1643059 TI - Growth patterns in the orbital region: a morphometric study. AB - Data for analysis of age-related changes in growth in the intercanthal (en-en) and biocular (ex-ex) widths were obtained from 1,594 healthy North American Caucasians in age groups from 1 to 18 years, divided equally between males and females. At 1 year, the degree of development of the intercanthal width reached 84.1%, and that of the biocular width 85.9% of adults in both sexes. The levels of growth achieved by 5 years of age rose to 93.3% in the intercanthal width and 88.1% in the biocular width, in both sexes. The average total growth increments achieved between ages 1 and 18 years were 5.2 mm in the intercanthal width and 12.5 mm in the biocular. The intercanthal width showed very little growth after 1 year of age; in contrast, the biocular width showed significantly greater growth increments both before and after 5 years of age. Rapid growth was observed between 3 and 4 years in the intercanthal width of both sexes. The age-related growth observed in the biocular width was small but continuous up to maturation time. The intercanthal width reached full maturation at 8 years in females and 11 years in males, and the biocular width at 13 years in females and 15 years in males. PMID- 1643060 TI - Growth patterns of the nasolabial region: a morphometric study. AB - Age-related growth changes in the nasolabial region were analyzed through six measurements taken between 1 year and 18 years of age in 1,593 North American Caucasians. By 1 year of age, the length of the cutaneous portion of the upper lip and the width of the nose showed the highest levels of development compared with their adult size, 80.3 and 79.5%, respectively. By 5 years, the developmental level of the nasolabial region except nasal tip protrusion approached their maturation level. Our nasal measurements indicated that growth of the nose between 5 and 18 years was significantly greater than that of the upper lip, which revealed significantly greater growth increments between 1 and 5 years of age. The cutaneous upper lip height reached its adult size in 3-year-old females (12.7 mm) and 6-year-old males (14.4 mm). Nose width and height were fully developed in females by age 12 and in males by age 14 or 15. Rapid growth occurred in the upper lip, nose height, and nasal tip protrusion between the ages of 1 and 4 years. Knowledge of these age-related morphologic variations within the nose and upper lip may be useful in planning the time and type of reconstructive surgery and in anticipating further change in the operated regions after the surgical reconstruction. PMID- 1643061 TI - Anthropometric growth study of the ear. AB - Age-related growth changes in the ear were analyzed by measuring the width and length of ears in 1,590 North American Caucasians between 1 year and 18 years of age. By 1 year, ear width reached 93.5% of adult size in both sexes, only 2.3 mm less than the mean value at 18 years. In contrast, ear length attained a developmental level of only 76.4% by 1 year in both sexes, requiring an increment five times greater (12.3 mm) to reach the size of the ear at 18 years of age. At 5 years, the developmental level in width (96.7%) was almost equal to that of an adult, while the length reached 86.6% in both sexes, and requires 8.2 additional millimeters to attain adult size. Annual growth increments in ear width are small, interrupted with a few periods of no growth. Ear length in males showed an early rapid growth rate (between 2 and 3 years); subsequent growth was generally limited, interrupted with short periods of no changes. The same growth pattern appeared in females. Ear width reached its mature size in males at 7 years and in females at 6 years; ear length matured in males at 13 years and in females at 12. At the time of maturation, the ear was shorter than at 18 years by a mean of 1.1 to 1.4 mm. PMID- 1643062 TI - A preliminary study of nasal airway patency and its potential effect on speech performance. AB - The relationship between nasal airway size and articulatory performance was studied in a group of cleft palate patients. Articulation analysis revealed that children with bilateral cleft lip and palate were nearly twice as likely to manifest compensatory articulations as children with unilateral cleft lip and palate or with cleft palate only. When subjects were grouped according to speech performance, aerodynamic assessment indicated that children with compensatory articulations had significantly larger nasal cross-sectional areas than children without compensatory articulations. The findings suggest that children with comparatively large nasal airways may be at increased risk for developing abnormal speech patterns. If these findings are confirmed by further research, such children may be candidates for relatively early palate repair. PMID- 1643063 TI - Is nasal airway size a marker for susceptibility toward clefting? AB - Johnston and Hunter (1989) reported that in monozygotic twins discordant for cleft lip +/- palate, the noncleft twins demonstrated what appeared to be a bimodal distribution of nasal cavity width. Two thirds showed reduced airway size and one third showed normal or slightly greater airway size. They suggested that the two-thirds group may represent reduced size of the medial nasal prominences and the other may represent underdevelopment of the maxillary prominence. We were particularly interested in the findings because the difference in distribution may represent differences in pathogenesis and therefore have etiologic significance. With this in mind we assessed nasal cross-sectional areas in 37 subjects with cleft lip or cleft lip +/- palate using the pressure-flow technique during breathing. A group of 72 noncleft individuals served as controls. As expected, the data revealed that subjects with clefts had a significantly reduced nasal airway (p = .0001). More important, the distribution of nasal airway size in the cleft group was similar to that reported by Johnston and Hunter (1989). This comparability suggests that it may be possible to assign most cleft lip +/- palate patients to a particular group. Since heredity may differ among the two groups (Chung et al., 1986), we may have a simple technique to assess the risk of occurrence for cleft lip +/- palate. PMID- 1643064 TI - Soft palate reflex: technical requirements and first results. AB - The present study describes technical prerequisites for soft palate reflex measurements and first results. Reflex measurements can be done using standard electromyographic methods. The data-processing system that records and processes the electromyographic signals was activated when the soft palate was stimulated by a newly developed device. The first results of objective soft palate reflex measurements in 15 healthy subjects show that the musculus levator veli palatini reacts to a mechanical stimulation of the soft palate with a contraction that can be measured electromyographically. The response latencies were constant in the individual subjects. In 12 subjects a minimum of 30 ms and a maximum of 61 ms was recorded. In one healthy subject, the reflex was activated only after 167 ms. No reflex could be evoked in two subjects. The stimulus was always supraliminal. Reaction time was longer following surface anesthesia of the oral mucosa. PMID- 1643065 TI - Correspondence between nasalance scores and listener judgments of hypernasality and hyponasality. AB - The relationship between nasalance scores and perceptual judgments of hypernasality and hyponasality was examined for 74 subjects (51 with cleft palate and 23 noncleft controls). Twenty-nine of the 51 subjects with cleft palate had received pharyngeal flap surgery. Predictive analyses were performed to assess the sensitivity, specificity, and efficiency of the Nasometer as a screening instrument. The overall relationship between perceptual judgments of hypernasality and nasalance scores was good for the nonflap subjects when a nasalance cutoff score of 26 was used. A sensitivity coefficient of 0.87 and a specificity coefficient of 0.93 were obtained. Ninety-one percent of the nasometry-based classifications accurately reflected listener judgments of hypernasality. The correspondence between nasalance scores and clinical judgments of hyponasality was also good for the nonflap subjects when a nasalance cutoff score of 50 was used. Ninety-one percent of these classifications were consistent with the listener judgments. Efficiency of nasometry was poorer for the flap subjects. PMID- 1643066 TI - Self-perception, social skills, adjustment, and inhibition in young adolescents with craniofacial anomalies. AB - This study examines the relationships between self-perception, social skills, overall adjustment, and social inhibition in 45 young adolescents with craniofacial anomalies (CFA). Self-perception, social skills, and inhibition scores are within the normal range while the average adjustment is 1.5 SD below the average. Regression analyses were conducted. Social skills and athletic competence are the best predictors of adjustment and accounted for 73.5% of the variance in adjustment. Adjustment of adolescents is associated with degree of inhibition, with more poorly adjusted adolescents displaying greater inhibition. Self-esteem did not predict to adjustment. The theoretical and clinical implications of these findings are discussed. PMID- 1643067 TI - Periodontal status of teeth adjacent to nongrafted unilateral alveolar clefts. AB - The purpose of this study was to compare the periodontal condition of teeth adjacent to the cleft with contralateral teeth in adult subjects with a nongrafted unilateral alveolar cleft. Periodontal parameters were evaluated in 18 subjects who had at least one tooth immediately adjacent to the cleft. For each tooth investigated, plaque index, gingival index, and probing depth were recorded and each tooth was assigned a mobility score. Width of attached gingiva and extent of recession was measured. Bone level was assessed using standardized magnified radiographs and a computerized digitizing system. The overall findings of this study support those of other studies and indicate that in individuals with a nongrafted alveolar cleft, teeth adjacent to the defect show signs of gingivitis but not of periodontal disease. The anatomic defect, eruption pattern, orthodontic tooth movements, and the presence of restorations appear to contribute to the reduced bone level on the central incisor adjacent to the cleft and to the presence of gingivitis. PMID- 1643068 TI - Fetal kleeblattschadel cranium: morphologic, radiographic, and histologic analysis. AB - The kleeblattschadel deformity is a rare craniofacial condition typified by its trilobed, cloverleaf skull. The pathophysiology of this process is controversial. The morphologic, radiographic, and histologic abnormalities identified in the cranial base of an 18-gestational-week fetus with kleeblattschadel skull have not been described previously. Recently, the intrauterine diagnosis of kleeblattschadel was established by serial ultrasonography and, based on this evidence, the fetus was aborted. The fetus was studied extensively. Standard radiographs and high-resolution CT scans were obtained. Three-dimensional, reformatted contour surface images were constructed from the CT scan data. The cranial base was examined grossly, radiographically, and histologically. Histologic microanatomic study concentrated on structures of the mid-sagittal cranial base from the occiput to the mid maxilla. The distorted cranial architecture in kleeblattschadel deformity has, in the past, been attributed largely to the cranial base deformity which secondarily distorts the developing brain. Our study, however, suggests that the calvarium itself may be the primary focus of abnormal events leading to synostosis. The findings in this study seem to be inconsistent with earlier theories about the abnormal development of craniodysostoses. PMID- 1643069 TI - Mandibular morphology and spatial position in patients with clefts: intrinsic or iatrogenic? AB - Lateral cephalometric films of operated (Op) and non-operated (Nop) patients with cleft lip and alveolus, cleft lip and palate or cleft palate only, were compared to determine whether the shape or position of the mandible is affected by lip and/or palate surgery. The sample included 204 adult cleft patients, Caucasians of both sexes with one of the following three cleft types: complete unilateral lip and alveolus (n = 50), complete unilateral lip and palate (n = 68), and isolated palate (n = 86). The comparison involved 113 cleft patients operated at the conventional timing and 91 cleft patients who had received no surgical or orthodontic treatment. Comparison was done in order to ascertain if the surgery performed had had any influence upon mandibular growth. The results indicated that, in all three cleft types, the surgery did not induce significant changes in the mandibular growth. PMID- 1643070 TI - Maxillary lateral incisor of subjects with cleft lip and/or palate: Part 1. AB - As a pilot study, dental casts of 30 patients with unilateral cleft lip and palate were selected and examined from the longitudinal data in the Department of Orthodontics, Kyushu University Dental Hospital. Dental casts of the anterior teeth were sectioned at right angles to the long axis of the tooth 2 to 3 mm below the incisal edge. The teeth were differentiated according to their cross sections. They were classed as lateral incisors or other types by the ratio of labiolingual diameter to mesiodistal diameter and the flatness labiolingually. Dental casts of 309 additional patients with cleft alveolus were examined subjectively based on above findings. In primary dentition, 183 of 184 teeth on the cleft side were incisal type. One tooth was canine type. In permanent dentition, 42 of 78 teeth on the cleft side were conical type, 20 teeth were intermediate type, and 16 teeth were incisal type. As a conclusion, the tooth on the cleft side is almost certain to be a lateral incisor, not a supernumerary canine tooth. As well, their form was normal in the majority of the primary dentition, but malformed in the permanent one. PMID- 1643071 TI - Maxillary lateral incisors of subjects with cleft lip and/or palate: Part 2. AB - Maxillary lateral incisors on the alveolar cleft were investigated in 431 cleft children registered in the Department of Orthodontics, Kyushu University Dental Hospital. The majority of primary maxillary lateral incisors were located on the distal side of the alveolar cleft in both unilateral cleft lip and alveolus (UCLA) and unilateral cleft lip and palate (UCLP) subjects. Permanent teeth in UCLA tend to be located distally, but in UCLP they tend to be congenitally absent (p less than .01). The majority of primary teeth had normal shapes; the majority of permanent teeth were of intermediate type or were missing congenitally. One third of the UCLA and one half of the UCLP subjects who had primary maxillary lateral incisors were not followed by permanent replacements. The location of the majority of permanent maxillary lateral incisors tallied with that of the primary ones except in four UCLA, ten UCLP, and two bilateral cleft lip and palate (BCLP) subjects. Four UCLA and ten UCLP subjects who had primary lateral incisors on the distal side were followed by their permanent successors on the mesial side. Three UCLP and one BCLP subjects had permanent maxillary lateral incisors even though they had no temporary predecessors. PMID- 1643072 TI - Association between adenoidectomy, velopharyngeal incompetence, and submucous cleft. PMID- 1643073 TI - Energy metabolism in islets of Langerhans. PMID- 1643074 TI - Amino acid transport System L in muscle cells: biochemical properties and its relation to protein synthesis. AB - Objectives were to characterize mechanisms and biochemical properties of transport systems responsible for the uptake of branched-chain amino acids (BCAAs) in muscle cells. Rat omega myoblasts (RMo) were grown to confluency and allowed to differentiate prior to conduct of transport assays. Myotubes concentrated cycloleucine (cLeu) in a sodium (Na)-free medium. The Na gradient independent transporter possessed high affinity (Km = 0.12 mM) and high capacity (Vmax = 6.4 nmol cLeu/mg protein per min). Cycloleucine transport was strongly inhibited by nonpolar neutral amino acids but not by alpha-aminoisobutyric acid or lysine. Myotubes possessed a Na gradient-independent trans-exchange mechanism. Hence, myotubes possess a System L-like transporter. In the second part of the study we determined that various inhibitors (KCN, oligomycin, iodoacetamide and cycloheximide) increased leucine transport. Their actions were not mediated by reductions in ATP concentration but were instead associated with changes in protein synthesis. Hence, regulation of muscle protein synthesis may also influence transporter activity. PMID- 1643075 TI - Changes in the nature of calcium transport systems on the porcine sperm plasma membrane during epididymal maturation. AB - Comparative studies of 45Ca(2+)-transport across the plasma membrane were performed using porcine caput, corpus and cauda epididymal sperm. The Ca(2+) uptake is dependent on the presence of the substrates for respiration and is sensitive to verapamil. The Ca(2+)-efflux is mediated by both Na(+)-dependent and -independent systems. In the immature sperm in caput epididymis, Na(+) independent efflux is predominant, but it is gradually replaced by Na(+) dependent efflux during the epididymal transit. The net activity of Ca2+ accumulation into sperm increases with the epididymal maturation. PMID- 1643076 TI - Double helix formation of phosphatidylcholine myelin figures. AB - Double helix formation of phosphatidylcholine myelin figures has been studied by use of optical microscopy. The winding of the double helices was looser than a geometrically possible one and the pitch was related proportionally to the outer radii of helical myelin figures. The regularity in the winding was explained in terms of the intermembrane binding energy and the bending elastic energy. PMID- 1643077 TI - Dual effects of calcium on ATP-sensitive potassium channels of frog skeletal muscle. AB - The block of ATP-sensitive K+ channels by ATP were studied in inside-out patches of frog toe muscles. Seal formation within Ca(2+)-free Ringer induces many open channels which can be irreversibly blocked by subsequent addition of Ca2+. However, such Ca(2+)-blocked and ATP-blocked channels can be influenced by the addition of ATP and Ca2+: the block by ATP is partially but irreversibly cancelled. PMID- 1643078 TI - The essential role of specific Halobacterium halobium polar lipids in 2D-array formation of bacteriorhodopsin. AB - The mechanism whereby bacteriorhodopsin (BR), the light driven proton pump from the purple membrane of Halobacterium halobium, arranges in a 2D-hexagonal array, has been studied in bilayers containing the protein, 1,2-dimyristoyl-sn-glycero-3 phosphocholine (DMPC) and various fractions of H. halobium membrane lipids, by freeze fracture electron microscopy and examination of optical diffractograms of the micrographs obtained. Electron micrographs of BR/DMPC complexes containing the entire polar lipid component of H. halobium cell membranes or the total lipid component of the purple membrane, with a protein-to-total lipid molar ratio of less than 1:50 and to which 4 M NaCl had been added, revealed that trimers of BR formed into an hexagonal 2D-array similar to that found in the native purple membrane, suggesting that one or more types of the purple membrane polar lipids are required for array formation. To support this suggestion, bacteriorhodopsin was purified free of endogenous purple membrane lipids and reconstituted into lipid bilayer complexes by detergent dialysis. The lipids used to form these complexes are 1,2-dimyristoyl-sn-glycerol-phosphocholine (DMPC) as the major lipid and, separately, each of the individual lipid types from the H. halobium cell membranes, namely 2,3-di-O-phytanyl-sn-glycero-1-phosphoryl-3'-sn-glycerol 1'-phosphate (DPhPGP), 2,3-di-O-phytanyl-sn-glycero-1-phosphoryl-3'-sn-glycerol 1'-sulphate (DPhPGS), 2,3-di-O-phytanyl-sn-glycero-1-phosphoryl-3'-sn-glycerol (DPhPG) and 2,3-di-O-phytanyl-1-O-[beta-D-Galp-3-sulphate-(1----6)-alpha-D- Manp (1----2)-alpha-D-Glcp]-sn-glycerol (DPhGLS). When examined by freeze-fracture electron microscopy, only the complexes containing 2,3-di-O-phytanyl-sn-glycero-1 phosphoryl-3'-sn-glycerol- 1'-phosphate or 2,3-di-O-phytanyl-sn-glycero-1 phosphoryl-3'-sn-glycerol-1'-sulphate, at high protein density (less than 1:50, bacteriorhodopsin/phospholipid, molar ratio) and to which 4 M NaCl had been added, showed well defined 2D hexagonal arrays of bacteriorhodopsin trimers similar to those observed in the purple membrane of H. halobium. PMID- 1643079 TI - Effect of the unsaturation of phospholipid acyl chains on leucine transport of Lactococcus lactis and membrane permeability. AB - The effect of the degree of unsaturation of the phospholipid acyl chains on the branched-chain amino acid transport system of Lactococcus lactis was investigated by the use of a membrane fusion technique. Transport activity was analyzed in hybrid membranes composed of equimolar mixtures of synthetic unsaturated phosphatidylethanolamine (PE) and phosphatidylcholine (PC) in which the number of cis double bonds in the 18-carbon acyl chains was varied. The accumulation level and initial rate of both counterflow and protonmotive-force driven transport of leucine decreased with increasing number of double bonds. The reduction in transport activity with increasing number of double bonds correlated with an increase in the passive permeability of the membranes to leucine. The membrane fluidity was hardly affected by the double bond content. It is concluded that the degree of lipid acyl chain unsaturation is a minor determinant of the activity of the branched chain amino acid transport system, but effects strongly the passive permeability of the membrane. PMID- 1643080 TI - Repulsive interactions and mechanical stability of polymer-grafted lipid membranes. AB - Liposome membranes containing lipids with covalently attached poly(ethylene glycol) (PEG-lipid) are currently being developed as drug delivery systems. These, so called, 'Stealth' liposomes have a relatively long half life (approximately 1 day) in blood circulation and show an altered biodistribution in vivo. The extended lifetime appears to result from a steric stabilization of the liposome by the grafted polymer. In order to characterize the surface structures that promote steric stability in such polymer-grafted lipid bilayer systems, we have used X-ray diffraction to measure the structural organization and interbilayer repulsion for lipid/cholesterol (2:1) bilayers incorporating 4 mol% of a PEG-lipid in which the molecular weight of the PEG moiety was 1900 g/mol. At this concentration, applied pressure versus interbilayer distance relations showed that the grafted polymer moiety extended approximately 50 A from the lipid surface and gave rise to a strong, slowly decaying repulsive pressure between membranes that opposed their close approach. Also, the pressure vs. distance relations were only modestly altered by changing the ionic strength of the medium (1 mM NaCl and 100 mM NaCl). Therefore, even though the PEG-lipid headgroup bears a negative charge, the long range pressure cannot be due primarily to an electrostatic double layer pressure. Measurements of lipid bilayer elasticity using micropipet manipulation showed that PEG-lipid did not change the cohesive properties of lipid/cholesterol liposomes which was consistent with the X-ray structural data showing that the PEG-lipid did not change the normal structure of the bilayer interior. From these data we conclude that the repulsive barrier properties of lipid-grafted PEG polymer chains originate mainly from a steric pressure and that this simple polymer steric stabilization is the basis for the extended in vivo circulation times observed for polymer-grafted liposomes. PMID- 1643081 TI - A sequential mechanism for the formation of aqueous channels by amphotericin B in liposomes. The effect of sterols and phospholipid composition. AB - The kinetics of formation of amphotericin B (AmB) aqueous pores in ergosterol containing DMPC or egg-PC liposomes was investigated using a stopped-flow method. The formation of aqueous pores by AmB occurred very rapidly (in milliseconds to seconds depending of the AmB concentration), and it was always preceded by the formation of transient, non-aqueous pre-pore structures. As anticipated, these non-aqueous pre-pore structures made the liposomes more permeable to urea without at the same time leading to a decrease of the reflection coefficient of urea or to an enhancement of glucose permeability. However, when liposomes were composed of egg-PC and cholesterol, the formation of non-aqueous and aqueous channels by AmB occurred after a lag time of several minutes. Such a time lag for AmB action was not observed in cholesterol-containing DMPC liposomes, an indication that the phospholipid composition is an important parameter in the formation of non aqueous channels by AmB. Both non-aqueous and aqueous channels were always formed at lower concentrations of AmB in liposomes containing ergosterol while higher concentrations were needed in cholesterol-containing liposomes. Measurements of the permeabilizing effect of AmB on liposomes prepared without sterols indicate that non-aqueous channels were formed in DMPC (but not in egg-PC) at polyene concentrations identical to that found for cholesterol-containing liposomes. No evidence of the formation of aqueous channels by AmB was found in pure DMPC liposomes. These data are consistent with the concept that AmB forms non-aqueous channels without the direct participation of sterol molecules. The initially formed non-aqueous channels subsequently interact with the sterols in the membrane to form aqueous channels, having an enlarged diameter. This sequential mechanism for the formation of AmB aqueous pores in liposomes provides a rationale for the understanding of the effect of both the phospholipid composition and type of sterol in the interaction of AmB with natural membranes and artificial bilayers. PMID- 1643082 TI - Site-directed antibodies as topographical probes of the gastric H,K-ATPase alpha subunit. AB - Gastric acid is secreted by an ATP-driven H+ and K+ exchanger (H,K-ATPase), an integral apical membrane protein of parietal cells. Although the primary structure of the enzyme is known, its higher order structure is uncertain. In order to acquire topographical probes of native, microsomal H,K-ATPase, synthetic peptides corresponding to the 17 amino-terminal (N-peptide) and 16 carboxyl terminal (C-peptide) residues of pig gastric H,K-ATPase alpha-subunit were coupled to keyhole limpet hemocyanin (KLH). Rabbits were immunized with peptide KLH conjugates and their sera were tested for specificity by enzyme-linked immunosorbent assay (ELISA), immunoblotting, and immunocytochemistry. All sera showed high ELISA reactivities with synthetic peptides, peptide-BSA conjugates, and microsomal H,K-ATPase adsorbed to microtiter wells (some titers greater than 1:10(4)). Immunoblots of H,K-ATPase resolved by SDS-PAGE showed both N-peptide and C-peptide antibodies reacting with a single 94 kDa band. All sera selectively stained parietal cells in pig gastric mucosal sections. Preimmune sera gave negative or weak signals in all assays. In competition ELISAs, N-peptide antibodies, but not C-peptide antibodies, were displaced from the corresponding bound synthetic peptides by added microsomal H,K-ATPase. One of the N-peptide antibodies inhibited H,K-ATPase activity by more than 50%; binding of this antibody was decreased when ATP or K+ were bound to the enzyme. These results indicate a cytoplasmically-oriented alpha-subunit N-terminus which may participate conformationally in the H,K-ATPase catalytic cycle, and suggest that antibodies against synthetic H,K-ATPase peptides are potentially useful probes of native microsomal H,K-ATPase topography. PMID- 1643083 TI - Electrical transients produced by the toad bladder in response to altered serosal composition at constant osmolality. AB - The effects of step-changes in the ionic composition of the serosal medium bathing the toad urinary bladder under voltage-clamped conditions have been studied. A decrease in the K+ concentration from 4 to 3 mmol/l in the serosal fluid increased transiently the transepithelial current which after 30 min returned to the initial value. The peak current was reached after 3 min. The current response of the bladder to the reverse step in K+ concentration, from 3 to 4 mmol/l was much smaller. Surprisingly, the partial replacement of Cl- with gluconate produced a transient increase in current. It is suggested that secondary active transport plays an important role in this phenomenon and leads to an increased apical Na+ conductance. The second phases of the biphasic responses to Na/K+ and Cl-/gluconate substitutions have been interpreted as osmotic effects. Since the exchange of solutions in these studies was isoosmotic but not necessarily isotonic, experiments were also performed with osmotic changes in the serosal fluid for the purpose of comparison. PMID- 1643084 TI - Triiodothyronine binding sites in the rat erythrocyte membrane: involvement in triiodothyronine transport and relation to the tryptophan transport System T. AB - The binding of L-triiodothyronine (T3) to rat erythrocyte membranes (ghosts and peripheral protein-depleted vesicles) was studied under equilibrium conditions. Ghosts contained high-affinity T3 binding sites whose dissociation constant (21 nM) was similar to the equilibrium-exchange Michaelis constant of T3 transport measured in ghosts. Each ghost contained about 8.10(3) high-affinity binding sites. The high-affinity T3 binding was stereospecific and was inhibited by L tryptophan (Trp) but not by L-leucine. The iodothyronine and amino acid specificity of binding is therefore similar to that of System T, the erythrocyte T3/Trp transporter. These Trp-inhibitable high-affinity T3-binding sites were also present in peripheral protein-depleted membrane vesicles, indicating that they are integral part of the membrane. Ghosts prepared from human erythrocytes, which have very low System T transport activities, contained no detectable Trp inhibitable high-affinity T3-binding sites. In rat erythrocyte ghosts, N ethylmaleimide inactivated both the binding and the transport of T3. This inactivation was blocked by T3 and Trp with similar efficiencies. Phenylglyoxal, an arginine residue modifier, also inhibited both high-affinity T3 binding and System T transport activity. It is concluded that the Trp-inhibitable high affinity T3-binding sites in the rat erythrocyte membrane are likely to be associated with System T. PMID- 1643086 TI - Identification of a novel beta-turn-rich repeat motif in the D hordeins of barley. AB - The amino acid sequence of the C-terminal part of a barley D hordein seed protein was deduced from the nucleotide sequence of a partial cDNA. It showed high homology with the HMW glutenin subunits of wheat, both proteins consisting predominately of repeated sequences. Whereas the wheat repeats are based on tri-, hexa- and nonapeptides that are rich in glycine, proline and glutamine, the D hordein also contains eleven copies of a novel unrelated motif: Thr-Thr-Val-Ser. The repeated sequences in the wheat glutenin subunits have been demonstrated to form an unusual spiral supersecondary structure based on beta-turns. Conformational analysis of the Thr-Thr-Val-Ser motif by secondary structure prediction and by circular dichroism spectroscopy of an 18 residue synthetic peptide demonstrates that it also forms beta-turns. Thus, D hordein may also have a spiral structure like that of HMW glutenin, despite the presence of a different repeat motif. This conservation of protein conformation in D hordein and the wheat glutenin subunits may indicate a structural role, perhaps in packing of the proteins within the protein bodies of the developing grain. PMID- 1643085 TI - Steroid-induced perturbations of membranes and its relevance to sperm acrosome reaction. AB - The interaction of progesterone, 17-alpha-hydroxyprogesterone, testosterone and estradiol with membrane vesicles prepared from phosphatidylserine (PS), from the total lipids of human and hamster spermatozoa, from the lipids of hamster spermatozoal plasma and acrosomal membrane and with the native membranes of hamster spermatozoa have been investigated by 90 degrees light scattering and fluorescence spectroscopy. The results indicate that progesterone decreases the fluidity of membranes, aggregates membrane vesicles, induces fusion of membrane vesicles and also renders them permeable to hydrophilic molecules like carboxyfluorescein. But, testosterone and estradiol at the same concentration had very little effect on membrane fluidity, membrane aggregation, fusion and leakage. The above membrane perturbing activities of the steroids is discussed in light of the recent findings that progesterone induces acrosome reaction in human and hamster spermatozoa [11,18]. PMID- 1643087 TI - Lipases from different sources vary widely in dependence of catalytic activity on water activity. AB - We have measured the rates of esterification in hexane catalysed by suspended immobilised lipases (triacylglycerol acylhydrolase, EC 3.1.1.3), with pre equilibration to known thermodynamic water activity (a(w)). There were important differences between the enzymes from five different microbes in their retention of activity at low a(w). That from Rhizomucor miehei showed over 40% maximal activity at an a(w) of 0.12, and that from Rhizopus niveus was also fairly active at low a(w). Lipases from other sources required higher a(w) values to show good activity, increasing in the sequence Humicola sp., Candida rugosa and Pseudomonas cepacia. The behaviour was generally similar to two very different support materials, anion-exchange resin and macroporous polypropylene. Comparison of the sequences of the homologous enzymes from Rh. miehei, Rh. niveus and Humicola sp. suggests that changes in charged residues in the 'hinge and lid' region of the structure may be significant in low a(w) tolerance. PMID- 1643088 TI - Regulation of the GM1-galactosidase supramolecular structure and catalytic activity in vitro. AB - Regulation of the supramolecular organization and the catalytic activity of GM1 galactosidase (EC 3.2.1.23) and neuraminidase (EC 3.2.1.18) from human kidney was studied in a system of hydrated reversed micelles of Aerosol OT in octane. It was shown that both the catalytic activity and the oligomeric structure of the GM1 galactosidase in reversed micelles depend on the [H2O]/[Aerosol OT] molar ratio (w(o)). GM1-galactosidase 64-67 kDa monomers, 260 kDa tetramers, and 660 kDa octamers were obtained in systems with w(o) = 0-20, 25-30 and 30-40, respectively. The association of GM1-galactosidase monomers into an octamer results in the cooperative increase in enzymatic activity. 'Protective protein', a component of the GM1-galactosidase-neuraminidase native complex, was found to improve this association significantly. PMID- 1643089 TI - X-ray diffraction studies on human tendon show age-related changes in collagen packing. AB - In this report, X-ray diffraction on native hydrated tendon is established as a monitor of human aging. X-ray diffraction patterns were recorded on toe extensor tendons of persons ranging from 1.6 years to 87 years old. All patterns show a set of 67 nm meridional reflections derived from the collagen fibril axial repeat, and the ratio of the intensities of the 16:17 orders showed a linear increase with age. The spacing of the equatorial maximum, which relates to the lateral packing of molecules in collagen fibrils, was also greater in older tendons. The observed changes in X-ray parameters follow those seen for rat-tail tendons subjected to in vitro non-enzymatic glycosylation. Age-related increases reported for the fluorescence of Maillard products and the concentration of the sugar-derived cross-link pentosidine are similar to the trends in X-ray parameters reported here. Our results support the cumulative nature of non enzymatic glycosylation in connective tissues during the human lifespan and indicate that structural changes accompany the chemical alterations. The X-ray parameters show a large degree of scatter for ages older than 60 years, suggesting other complicating factors are present. Studies on a small number of diabetic tendons show small, but not significant, increases compared to age matched controls. PMID- 1643090 TI - Histone H1a subtype presents structural differences compared to other histone H1 subtypes. Evidence for a specific motif in the C-terminal domain. AB - Following a previous isolation by reverse-phase HPLC of five histone H1 subtypes from adult rat liver, purity of three of them, H1a, H1b and H1d (according to Lennox's nomenclature), was achieved. Structural features of these three subtypes were investigated. Partial cleavage of these subtypes by endoproteinase Glu-C showed a different behavior of the H1a subtype when compared to the H1b and H1d subtypes. Under the conditions used in this work, the H1b and H1d subtypes present three major sites accessible to the endoproteinase Glu-C, while the H1a subtype presents only one major site accessible to the proteinase. Partial N terminal sequence of the different fragments obtained after proteolysis indicated that the two H1b and H1d subtypes were cleaved inside the globular domain (Glu 54,-75) and between the globular domain and the C-terminal one (Glu-116). The H1a subtype was only cleaved between the globular domain and the C-terminal tail (Glu 116), though Glu-54 and Glu-75 sites were present. These results would suggest some differences in the conformation of these proteins. Furthermore, the partial determined sequences of H1b and H1d showed 85% similarity to each other (the main differences were threonine residues instead of alanine residues in the C-terminal domain) while H1a was only 60% similar to H1b and H1d, for the sequences which aligned. The strongest differences between the H1a subtype and the two other subtypes were observed in the first amino acid residues of the C-terminal domain. The 117-126 amino acid residues (SKASTTKVTV) of H1a were quite different from those of H1b and H1d. This sequence, which showed a number of serine and threonine residues, was not found in any other histone sequence, after consultation with data bases. This H1a subtype was a minor component in adult liver (2.4%). As it was described in testis as a major component, testis histone H1 proteins were fractionated onto reverse-phase HPLC under the same conditions as those used for histone H1 proteins from liver. The pure testis H1a fraction was submitted to the endoproteinase Glu-C digestion. The pattern digestion was the same as that observed for liver H1a. The two 44-76 and 117-126 determined amino acid residues of H1a from testis were strictly identical to those of liver H1a. We demonstrate that H1a is the same protein in liver and testis and we give evidence for a specific motif SKASTTKVTV (117-126 residues) in the sequence of the C-terminal domain.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1643091 TI - Enzymatic methylation of heterogeneous nuclear ribonucleoprotein in isolated liver nuclei. AB - Protein N-methyltransferase activity has been studied in the rat liver nuclei, using recombinant heterogeneous nuclear ribonucleoprotein particle protein A1 and histone as the methyl acceptors. The hydrolysates of these two enzymatically [methyl-3H]-labeled proteins, however, yielded different patterns of methylated amino acids on HPLC analysis: NG-monomethylarginine (92%) and NG-NG-dimethyl (asymmetric) arginine (6.5%) were the major methylated amino acids identified in the protein A1, whereas epsilon-N-methylated lysine derivatives constituted a predominant portion (71%) of the methylated amino acids in histone. When liver extracts isolated from rats fed a methyl deficient diet were assayed, the methyl accepting activity of protein A1 increased 64% over the control (rats fed normal diet), while that of histone increased 260%. Partial hepatectomy induced a 7.9 fold and 2.3-fold increase in the protein A1 methylase activity after 24 and 48 h of regeneration, respectively. These results, together with the fact that myelin basic protein-specific protein methylase I does not significantly methylate protein A1, indicate the presence of an enzyme in the rat liver nuclei which methylates the protein A1. PMID- 1643092 TI - A variety of catalases and bromoperoxidases in genus Pseudomonas and their characterization. AB - A survey of bromoperoxidase in some Pseudomonas strains revealed that they contain different types of bromoperoxidase, catalase-bromoperoxidase and catalase. Although all Pseudomonas strains exhibited catalase activity, the enzyme isolated from P. pyrrolnitrica was named catalase-bromoperoxidase, because it catalyzed not only a catalase reaction, but also the bromination of monochlorodimedone. Except heme-type catalase-bromoperoxidase, this strain contained four isoenzymes of general nonheme bromoperoxidase, and their molecular weights were about 73,000. On the other hand, P. putida and P. aeruginosa had the usual heme-type catalase, but they differed in molecular weight and pI value. Both strains also had a nonheme bromoperoxidase which catalyzed the bromination of monochlorodimedone and aniline, and the molecular weight of each enzyme was 68,000 for P. putida and 86,000 for P. aeruginosa. Considering the results reported by Van Pee et al. [1] and Weisner et al. [2], regarding the haloperoxidases of Pseudomonas, the genus was revealed to contain a wide variety of bromoperoxidase and catalase. PMID- 1643093 TI - Conformational studies of the 'RGD' containing peptide echistatin and close analogs by circular dichroism and fluorescence. AB - Echistatin, one of the smallest and most active natural disintegrins, and its [Trp13]echistatin, [Trp27]echistatin, [Phe13,Trp31]echistatin analogs have been investigated by far-UV circular dichroism spectroscopy and fluorescence spectroscopy. All analogs inhibited ADP-stimulated platelet aggregation with EC50 values between 30 and 50 nM. The analogs were related closely, both in the CD spectral properties, characteristic of turn conformations, and in the location of isodichroic points connected to conformational transitions upon temperature increase. The low fluorescence quantum yield for Trp13 of 0.018, which could be enhanced 2.7-fold by DTT reduction of the peptide, is ascribed to a close proximity of this Trp13 residue to a disulfide bond. Calculation of the efficiency of fluorescence resonance energy transfer (FRET) yielded distances of 11.5 +/- 0.8 A for Tyr31-Trp27 in [Trp27]echistatin, and more than 15 A for Tyr31 Trp13 in [Trp13]echistatin, in good agreement with the structure of echistatin deduced from earlier NMR-molecular modeling studies. Both Trp13 and Trp27 in the respective analogs were quenched effectively by acrylamide with bimolecular quenching constants of 3.36 x 10(9) M-1 s-1 and 3.72 x 10(9) M-1 s-1, respectively. Iodide anion had negligible quenching effect on Trp13, despite high exposure of this residue to water, but was only 2-fold less efficient than acrylamide in quenching Trp27 fluorescence. Steady-state fluorescence anisotropy data, together with mean fluorescence lifetimes of 1.25 ns for Trp13 and 3.84 ns for Trp27 derived from full fluorescence lifetime decay analyses, yielded long rotational relaxation times of 1.39 +/- 0.18 and 1.35 +/- 0.17 ns, respectively, for these residues comparable to the expected overall rotation time of the peptides. The 'RGD'-containing loop appears to be restricted in movement on the nanosecond timescale with respect to the compact core of the peptide. PMID- 1643094 TI - Purification and characterization of major glycoproteins, PAS-6 and PAS-7, from bovine milk fat globule membrane. AB - Two major glycoproteins (PAS-6 and PAS-7) from bovine milk fat globule membrane were selectively extracted with urea and KCl, co-purified by repeated gel filtration on Sephacryl S-200 and then separated by affinity chromatography on concanavalin A-agarose column. The two purified glycoproteins showed a single band by SDS-PAGE, and their molecular masses were estimated to be 50 kDa for PAS 6 and 47 kDa for PAS-7. Both PAS-6 and PAS-7 were resolved several variants by analytical isoelectric focusing. These were shifted to a single band at pI 6.2 for PAS-6 and at pI 6.5 for PAS-7 by neuraminidase. PAS-6 contained 7.1% and PAS 7 5.5% of carbohydrate; the molar ratio of fucose:mannose:galactose:N-acetyl galactosamine:N-acetyl glucosamine:sialic acid was 1.0:3.0:2.0:6.1:5.0:1.3 for PAS-6 and 1.0:3.1:2.2:0:4.1:1.1 for PAS-7. Mild alkaline treatment and affinity to various lectins indicated that PAS-6 had O- and N-linked oligosaccharide chains, while PAS-7 had only the N-linked type. The major amino acid residues of PAS-6 were Glu, Ser and Gly, and those of PAS-7 were Asp, Glu, Gly and Leu. The N terminal amino acids of both glycoproteins were blocked. PAS-6 and PAS-7 digested with trypsin had a different peptide map, two major peptides having the same retention time on HPLC and being common to PAS-6 and PAS-7 having the same amino acid sequences of H-Gln-Ser-Gly-Asn-Lys-Asn-Pro-Ser-Glu-Ile-Ser-OH and H-Ile-Phe Pro-Gly-Asn-Met-Asp-Asn-Ser-His-Lys-OH. PMID- 1643095 TI - Identification of the histidine residue in Escherichia coli isocitrate lyase that reacts with diethylpyrocarbonate. AB - Escherichia coli isocitrate lyase was inactivated by diethylpyrocarbonate in a pseudo-first-order process. The enzyme was completely inactivated by modification of a single histidine residue, but slower modification of further residues also occurred. The substrate, isocitrate, and products, glyoxylate and succinate, protected against inactivation by diethylpyrocarbonate but this was not simply due to binding at the active site. Treatment of the inactivated enzyme with hydroxylamine led to only partial recovery of activity. Diethylpyrocarbonate also reacted with sulphydryl groups in isocitrate lyase, as judged by titrations with Nbs2, but this reaction was not responsible for the failure of hydroxylamine to reactivate the enzyme fully. The reactivity of isocitrate lyase to diethylpyrocarbonate declined with pH, following a titration curve for a group of pKa 6.1. Isolation and sequencing of ethoxyformylated peptides showed that the major site of modification by diethylpyrocarbonate was histidine residue 306. PMID- 1643096 TI - Concentration and distribution of apolipoproteins A-I and E in normolipidemic, WHHL and diet-induced hyperlipidemic rabbit sera. AB - Two sandwich-type enzyme immunoassays have been developed to measure apolipoproteins A-I and E in rabbit serum. Specific goat antibodies were purified by affinity chromatography and used both for coating and for preparing antibody peroxydase conjugates. The sensitivity of these assays is sufficient to allow studies of apo A-I and E distribution in lipoproteins fractionated by gel filtration from 50 microliters of serum. In WHHL rabbits, apo A-I is 5-fold lower (5.2 +/- 2.5 mg/dl) and apo E is 8-fold higher (9.9 +/- 3.5 mg/dl) than in normolipidemic rabbits (29 +/- 4.3 mg/dl and 1.3 +/- 0.5 mg/dl, respectively). In hyperlipidemic rabbits, fed 2 months on a 0.5% cholesterol diet, the apo A-I level was similar (32 +/- 12 mg/dl) to that of normolipidemic rabbits, but the apo E level is 12-fold higher (15.1 +/- 5.5 mg/dl). In addition, HDL particles were enriched with cholesterol and apo E. The bulk of apo E and cholesterol is located in large beta-VLDL in diet-induced hyperlipidemia, whereas they are mainly located in smaller size beta-VLDL in WHHL rabbits. In normolipidemic rabbits apo E occurs mainly in HDL, and cholesterol is distributed in the main three lipoprotein fractions VLDL, LDL and HDL. Interestingly, HDL of WHHL rabbit are deficient in apo A-I. These results are compatible with profound perturbations of lipoprotein composition and metabolism in atherogenic hyperlipidemia. PMID- 1643097 TI - Peroxidation and phospholipase A2 hydrolytic susceptibility of liposomes consisting of mixed species of phosphatidylcholine and phosphatidylethanolamine. AB - The relationship between lipid peroxidation and phospholipase A2 (PLA2) hydrolytic activity was studied using unilamellar vesicles (liposomes) as model membranes. Hydrolytic specificity was examined using vesicles prepared with pure bovine heart phosphatidylcholine (PC), bovine heart phosphatidylethanolamine (PE), or mixtures of these phospholipids, using two preparative procedures, i.e., sonication or extrusion. Lipid peroxidation was induced by incubating vesicles with cumene hydroperoxide and hematin at 37 degrees C. Determinations of the extent of peroxidation by means of diene conjugate content derived from second derivative spectra or by polarographic measurement of oxygen consumption rates provided a basis for comparing the extent of peroxidation of each phospholipid species to their subsequent hydrolysis by PLA2 (from Crotalus adamanteus). The extent of hydrolysis was determined through the release of arachidonic acid from either PC or PE. The PE distribution among the outer vs. inner leaflet of the membrane bilayer was nearly equal in sonicated vesicles, whereas most of the phospholipid was incorporated into the inner leaflet in extruded vesicles. The proportion of PE found in the inner leaflet progressively increased as the ratio of PE to PC increased in both sonicated and extruded vesicle preparations. Lipid peroxidation had no effect on PE distribution under the conditions examined. There was a clear preference for PC peroxidation for all vesicle compositions tested and PC was preferentially hydrolyzed by PLA2. This effect is proposed to result from a perturbation of membrane structure following peroxidation with assimilation of PC into PLA2-susceptible domains whereas PE peroxidation and hydrolysis is less affected in mixed PC/PE vesicles. Lipid peroxidation imposes an additional hydrolytic susceptibility over the effects exerted through the mixing of these phospholipids which is based on structural changes rather than formation of specific substrates for PLA2. PMID- 1643098 TI - Tea catechins decrease micellar solubility and intestinal absorption of cholesterol in rats. AB - A(-)-epicatechin (EC) and (-)-epigallocatechin (EGC) mixture and a mixture of their gallates (ECG and EGCG, respectively) markedly lowered lymphatic cholesterol absorption in rats with a cannulated thoracic duct. A mixture of ECG and EGCG was more effective in reducing cholesterol absorption than the EC and EGC mixture. These catechins also tended to decrease lymphatic absorption of triacylglycerols, although not so pronounced as in cholesterol absorption. An in vitro study on micellar solubility of cholesterol showed that these catechin mixtures precipitated cholesterol solubilized in mixed bile salt micelles in a dose-dependent manner. A mixture of ECG and EGCG more effectively precipitated micellar cholesterol than a mixture of EC and EGC. When purified EC, EGC, ECG and EGCG were used, EGCG was more effective in precipitating micellar cholesterol than ECG. The effect of EC and EGC was comparable and weaker than their gallate esters. The bile acid concentration in the micelles was not affected by these catechins. A positive correlation was observed between the amount of coprecipitated EGCG and cholesterol. These results clearly show that tea catechins, in particular their gallate esters, effectively reduce cholesterol absorption from the intestine by reducing solubility of cholesterol in mixed micelles. The observation accounts for the hypocholesterolemic effect of tea catechins. PMID- 1643099 TI - Lower levels of lipid peroxidation in human platelets incubated with eicosapentaenoic acid. AB - The modulatory effects of eicosapentaenoic acid (EPA) on platelet arachidonic acid (AA) metabolism were applied to an in vitro model of oxidant stress. Unstimulated normal human blood platelets were first treated with a thiol oxidizing agent, azodicarboxylic acid bis(dimethylamide) (diamide) (1 microM), and then incubated with a low concentration of EPA (100 nM). Diamide treatment led to a lower alpha-tocopherol content compared to control. Formation of MDA, a marker of the overall lipid peroxidation, as well as formation of 12 hydroxyeicosatetraenoic acid (12-HETE), the 12-lipoxygenase end-product of AA, were both higher in diamide-treated platelets. Subsequent incubation of diamide treated platelets with EPA counteracted the effects of oxidant stress induced pharmacologically by diamide. Interestingly, EPA prevented the alpha-tocopherol level from falling and the overall lipid peroxidation from increasing as it did during diamide treatment. In particular, incubation of diamide-treated platelets with EPA led to significantly lower amounts of 12-HETE. Conversely, preincubation of platelets with 100 nM EPA protected cells from oxidizing effects induced by diamide treatment, either on the level of lipid peroxides or on the antioxidant status. These results indicate that, in this particular model, EPA permitted platelets to have control levels of tocopherol, MDA and 12-HETE despite diamide treatment. Low concentrations of EPA might have prevented the increase of lipid hydroperoxides and especially the transient accumulation of 12 hydroperoxyeicosatetraenoic acid (12-HPETE). PMID- 1643100 TI - Glycosylation of lipoprotein lipase in human subcutaneous and omental adipose tissues. AB - Human adipose tissues from the abdomen (subcutaneous), thigh (subcutaneous) and omentum were incubated for 2 h with [35S]methionine. Then glycosylation of lipoprotein lipase (LPL) was analyzed by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of endoglycosidase H (endo H)-digested subunits of the 35S-labeled lipase. Adipose tissues from the abdomen, thigh, and omentum all synthesized LPL subunits with Mr = 57,000 composed of two types of subunits. One type was partially endo H-sensitive yielding a product with Mr = 55,000, indicating that it had one endo H-resistant and one endo H-sensitive oligosaccharide chain. The other type of subunit was totally endo H-sensitive yielding a product with Mr = 52,000. Subcutaneous adipose tissues contained nearly equal amounts of partially and totally endo H-sensitive subunits of LPL, whereas omental adipose tissues contained mainly partially endo H-sensitive subunits of LPL. PMID- 1643101 TI - Observation of the inverted hexagonal phase of lipids by scanning tunneling microscopy. AB - Scanning tunneling microscopy (STM) has been used in direct observations of the inverted hexagonal phase of several lipids, such as cardiolipin (CL) in the presence of Ca2+, soybean PE, DOPE and a binary system of CL and DMPC as well. Single tube-like structures, bundles of tubes and the cross-sectional view of the HII phase can clearly be seen at room temperature in a near natural state of these lipids. The success of this study shed some light on the applicability of STM in the investigation of lipid polymorphism and its role in the function of biological membranes. PMID- 1643102 TI - Glucocorticoids inhibit TNF alpha-induced cytosolic phospholipase A2 activity. AB - The cytosolic phospholipase A2 (PLA2) was characterized in the human epithelial carcinoma cell line HEp-2 by its apparent molecular mass (about 80 kDa); its in vitro activation by micromolar concentrations of calcium; and its calcium dependent association with cellular membranes. The activity of this enzyme was induced by an overnight incubation with tumor necrosis factor alpha (TNF alpha). Glucocorticoids only moderately reduced PLA2 activity in control cells, but completely inhibited the TNF alpha-induced increase in the activity of the high molecular-weight cytosolic PLA2. PMID- 1643103 TI - Fibric acid derivatives: effects on the synthesis of isoprenoid lipids in cultured human lymphocytes. AB - Fibric acid derivatives have been demonstrated to reduce circulating lipoprotein and triacylglycerol concentrations and to inhibit hydroxymethylglutaryl CoA reductase, a key regulatory enzyme of cholesterol biosynthesis. This study describes the effect of four fibric acid derivatives on the biosynthesis of isoprenoid products from acetate and mevalonate in Molt-4 cells, a human leukemic T-lymphocyte cell line. The isoprenoids analyzed were cholesterol as well as dolichol and ubiquinone, alternative products of the branched isoprenoid biosynthetic pathway. None of the fibric acid derivatives showed significant effects on the synthesis of cholesterol from acetate or mevalonate and there was little change in the flux of these metabolites into either dolichol and ubiquinone compared to cells grown in drug-free medium. Therefore, in contrast to the reported inhibitory effects of fibric acids on hepatic sterol synthesis in rats and humans and on hydroxymethylglutaryl CoA reductase activity in human nonmalignant lymphocytes, our results show that these drugs do not significantly affect any of the post-reductase enzymes in the branched metabolic pathways leading from acetate to dolichol, ubiquinone and cholesterol in short term culturing of human malignant lymphocytes. PMID- 1643104 TI - The visceral yolk sac--an important site of synthesis and secretion of apolipoprotein B containing lipoproteins in the feto-placental unit of the rat. AB - Rat fetuses exhibit a high serum LDL concentration at term. Delivery caused a marked decrease of the LDL apolipoprotein (apo) B concentration independent of whether this occurred on days 21, 22 or 23 of gestation. The interruption of the yolk sac circulation by a ligature in situ for 6 h led to the same alterations of the LDL-apo B concentration as Caesarean section. Immunoelectronmicroscopic studies provided evidence that the epithelial cells of the visceral yolk sac exhibited electron dense LDL-sized and apo B containing particles which were localized over the compartments of the Golgi complexes, endoplasmatic reticulum, secretory vesicles and intercellular spaces, but not over the cell nuclei, mitochondria or lysosomes. ApoB containing LDL-sized particles could be obtained by ultracentrifugation from the disrupted material of the microsomal fraction of yolk sac homogenates. Isolated segments of the yolk sac membranes were capable to secrete apoB containing lipoproteins floating in the d less than 1.020 g/ml as well as in the d = 1.020-1.064 g/ml fraction with a 10-fold higher amount of apoB in the higher density class. Incorporation experiments with [35S] methionine gave evidence that these lipoproteins were at least partially provided with newly synthesized apoB predominantly found in the LDL fraction. The size of the negatively stained particles in the d = 1.020-1.064 g/ml fraction secreted from yolk sac segments corresponded to that of LDL from fetal rat serum. In contrast their acylglycerol content was significantly higher, whereas the percentage contribution of total cholesterol and protein was markedly reduced in comparison with serum LDL of the fetus. In summary, biochemical and ultrastructural studies provide clear cut evidence that the rat yolk sac is able to synthesize and to deliver apo B containing lipoproteins in the density ranges of VLDL, IDL and particular of LDL thus contributing to the supply of serum lipoproteins in the rat fetus. By recalculation of recent tracer kinetic data (Plonne et al. (1990) J. Lipid Res. 31, 747) using a mathematical step function model it was possible to assess the contribution of the rat yolk sac to the LDL influx into the fetal serum. PMID- 1643105 TI - Calorimetric studies of lipid tubule formation from ethanol-water solutions. AB - We have used differential scanning calorimetry to systematically investigate the thermal formation of hollow cylindrical crystalline microstructures or 'tubules' upon cooling a diacetylenic phosphatidylcholine (1,2-bis(10,12-tricosadiynoyl)-sn glycero-3-phosphocholine) dispersed in varying volume fractions of ethanol/water. Tubule formation is characterized by a large exothermic event, observed upon cooling the lipid in 60-80% ethanol. The enthalpy of the transition was observed to be highest in this window of tubule formation (128-138 J/g) which is significantly higher than previously reported values for the enthalpy of tubule formation in water (90 -95 J/g). The enthalpy associated with the formation of tubules in 70% ethanol was also found to be strongly dependent on the efficiency of tubule formation and decreased as the number density of tubules decreased. A significant decrease in tubule number density could be brought about by increasing the lipid concentration of the 70% ethanol solution. Tubule number density was maximized at lipid concentrations between 0.5 and 2 mg/ml in 70% ethanol. Examination of the C-H stretch region from infrared spectra of the lipid below the phase transition, indicate that the intramolecular chain order-disorder is similar, regardless of the fraction of ethanol. The higher transition enthalpy for the melting of tubules in 60-80% ethanol (compared to water) implies that the high-temperature phase from which the tubules form in ethanol is more disordered than the lamellar liquid crystalline phase from which tubules form in water. PMID- 1643106 TI - Use of specific polyclonal antibodies to detect heterogeneous lipases from Geotrichum candidum. AB - Geotrichum candidum CMICC 335426 was previously shown to produce two lipases termed lipase A and lipase B, lipase B being highly specific for hydrolysis of esters of cis-delta 9 fatty acids. We now describe the isolation of polyclonal antibodies specific for lipase A and lipase B. These antibodies were used in Western blotting techniques to detect the appearance of the lipases during the course of the fermentation of G. candidum CMICC 335426. A and B were found to be produced simultaneously in the extracellular medium at the start of the growth phase. The two lipases were always present at similar levels in the medium. The specific antibodies were then used to detect the presence of A- and B-like lipases in crude lipase samples from other strains of G. candidum. The lipases were found at different levels in all these samples, and the specificities of the crude lipases varied significantly from one strain to another. Differences in specificity could therefore be explained by different levels of specific (B-type) and non-specific (A-type) lipases in the medium. This was verified by purifying A and B-type lipases from the G. candidum strain ATCC 34614. PMID- 1643107 TI - cDNA sequence and alternative mRNA splicing of surfactant-associated protein C (SP-C) in rabbit lung. AB - An 784 base pair (bp) copy DNA (cDNA) for the low molecular weight hydrophobic surfactant-associated protein C (SP-C) has been isolated from a lambda gt11 cDNA library constructed from fetal rabbit lung mRNA. The cDNA, which coded for a 193 amino-acid proprotein with 6 bp 5' and 193 bp 3' untranslated segments, possesses considerable nucleic acid and predicted amino-acid homology with previously reported SP-C cDNAs. The predicted amino-acid sequence of the 35 amino-acid mature polypeptide shares 94-97% identity with human, rat and mouse SP-C and is 88-91% homologous to the mature proteins from bovine, porcine and canine lung. The last 12 amino acids of mature SP-C are highly hydrophobic and invariant. Alignment of the rabbit and human nucleic acid sequences required introduction of a 27 bp gap in the rabbit sequence at a site corresponding to the exon-intron junction of the 5th exon of the human genomic sequence. Since previous studies have identified differential splicing at the 5' and 3' ends of the human 5th exon, we investigated the potential existence of alternative splicing of rabbit SP-C mRNA. Reverse transcription (RT) of total RNA followed by polymerase chain reaction (PCR) was used to establish the relative abundance of alternative splicing products from fetal and adult lung and from rabbit kidney, placenta and liver. The relative abundance of the 250, 280 and 350 bp bands observed was the same in lung and other tissues. PCR amplification of genomic rabbit DNA indicated that the 350 bp fragment corresponds to the unspliced nascent transcript. The lack of developmental or tissue-specific abundance patterns implies the absence of secondary influences on SP-C mRNA polymorphism. Indeed, free energy of formation calculations predicted the presence of hairpin structures favouring formation of the more abundant 250 bp form. These observations plus the absence of any effect of alternative splicing on SP-C protein structure led us to conclude a physiological role is unlikely. PMID- 1643108 TI - Reversibility of the activation of soluble phospholipase A2 on lipid bilayers: implications for the activation mechanism. AB - The time-courses of hydrolysis of large vesicles of dipalmitoylphosphatidylcholine were compared using four species of phospholipase A2 (Agkistrodon piscivorus piscivorus, Crotalus adamanteus and Naja naja venoms and porcine pancreatic). In all four cases, the hydrolysis rate suddenly increases 10 to 100-fold at the time (tau) when a specific mole fraction of reaction products has accumulated. The intrinsic fluorescence emission of the three venom enzymes also increases suddenly at time tau. Both the activation and the fluorescence change are reversible with a half-time of about 50 s for the activity and 2 to 6 s for the fluorescence. These reversal rates and the vesicle concentration dependence of tau are considered for monomer and dimer enzyme activation models. Apparently, at least three states of the enzyme exist beyond the initial unbound state: (1) inactive and bound, (2) inactive with high fluorescence and (3) active. The dimer model already contains the necessary number of states but requires that the activation rate be much lower than the reversal rate to account for the vesicle concentration dependence of tau. Success of the monomer model requires an enzyme state additional to those proposed previously. Although these results do not exclude either the monomer or dimer models conclusively, they do impose important constraints on each model. PMID- 1643110 TI - Molecular cell research. PMID- 1643109 TI - Characteristics and regulation of ganglioside-induced elevation of free cytoplasmic Ca2+ in human blood platelets. AB - We have found that gangliosides GD3 and GM3 induced rapid, reversible elevation of free cytoplasmic Ca2+ in fura-2-loaded human blood platelets. The effect persisted in Ca(2+)-free medium, indicating that gangliosides stimulated mobilization of intracellular stores. The action of gangliosides was concentration-dependent with EC50 of about 1 microM. The Ca(2+)-mobilizing effects of gangliosides were potentiated by epinephrine and inhibited by substances inducing activation of protein kinase C and cAMP-dependent protein kinases. Acidic phospholipids partially mimicked the Ca(2+)-mobilizing effects of gangliosides indicating that lipid head charge is essential for this activity. While the elevation of [Ca2+]i produced by arachidonic acid was almost completely blocked by aspirin pretreatment, the effects of gangliosides were diminished only 2-fold, indicating that gangliosides activate both aspirin-sensitive and aspirin insensitive mechanisms of [Ca2+]i elevation. PMID- 1643111 TI - Hydroxyurea induces apoptosis and regular DNA fragmentation in a Burkitt's lymphoma cell line. AB - Hydroxyurea (HU) is an S-phase-specific cytotoxic drug used in the clinical treatment of haematological malignancies. HU treatment has been shown to lead to accumulation of short DNA fragments which show direct correlation with cytotoxicity. Specific regular DNA fragmentation is a biochemical feature of apoptosis (programmed cell death) in some systems. We investigated the effect of HU on a neoplastic (Burkitt's lymphoma) cell line (BM13674) in vitro to determine the role of apoptosis in HU action. HU produced growth inhibition and cell death by apoptosis in BM13674 cells. Low dose HU (66 and 131 mumol/l) gave a growth inhibition effect only with no apoptosis being induced. Higher doses (0.66-13 mmol/l) induced apoptosis in a dose-dependent manner. Regular DNA fragmentation was detected by agarose gel electrophoresis of DNA and this correlated in time with the onset of apoptosis detected by light and electron microscopy. The results do not exclude the possibility that HU directly induces DNA strand breaks, which then initiate apoptosis and accompanying regular fragmentation of DNA in the apoptotic cells. PMID- 1643112 TI - Expression of chondroitin sulfate as a unique type of proteoglycan on the cell membrane of multipotential and committed hemopoietic progenitor cells. AB - Proteoglycans are increasingly implicated as a major factor in the regulation of hemopoiesis. They are generally synthesized by stromal cells and released to the extracellular matrix. More recently the ability of hemopoietic progenitor cells to synthesize proteoglycans has come into focus. In the present study we maintained 3 cloned factor-dependent hemopoietic progenitor cells (B6 and F-mix which are multipotential and F-2 which is bipotential) in liquid culture. The cells were pulse-labeled with 35SO4 which becomes incorporated into the glycan side-chains of proteoglycans. We then studied subcellular distribution and chemical characterization of the newly synthesized proteoglycans. All 3 cell lines synthesized chondroitin sulfate as a unique type of proteoglycan as identified by gel filtration on a Sepharose CL-4B column followed by chondroitinase ABC cleavage of its glycosaminoglycan. This single type of proteoglycan was compartmentalized into intracellular, membrane-associated and extracellular pools. Its density on the membrane appeared to be a function of the differentiation state of the cell. The functional significance of membrane associated proteoglycan in hemopoietic progenitor cells appears to be underestimated and requires further investigation. PMID- 1643113 TI - A thousand and two protein tyrosine phosphatases. PMID- 1643114 TI - 1,25-(OH)2D3 and 24,25-(OH)2D3 regulation of arachidonic acid turnover in chondrocyte cultures is cell maturation-specific and may involve direct effects on phospholipase A2. AB - Previous studies have shown that 1,25-(OH)2D3 stimulates phospholipase A2 (PA2) activity in growth zone chondrocytes (GC), but has no effect on the resting zone chondrocyte (RC) enzyme activity. 24,25-(OH)2D3 inhibits the RC enzyme but has no effect on the GC. This study examined whether the vitamin D metabolites affect arachidonic acid turnover in their contra-target cell populations. Incorporation and release of [14C]arachidonate was measured at various times following addition of hormone. Acylation and reacylation were measured independently by incubating with p-chloromercuribenzoate. The results demonstrated that 1,25-(OH)2D3 has no effect on arachidonic acid turnover in RC, but stimulates turnover in GC. In contrast, 24,25-(OH)2D3 stimulates arachidonic acid turnover in RC, but inhibits both incorporation and release in GC. To determine whether direct interaction with PA2 is one mechanism by which 1,25-(OH)2D3 and 24,25-(OH)2D3 regulate arachidonic acid release, snake venom (Niger niger) PA2 was incubated with the vitamin D metabolites. Enzyme specific activity was inhibited by 24,25-(OH)2D3 and stimulated by 1,25-(OH)2D3 in a time- and dose-dependent manner. These results suggest that at least part of the direct effect of vitamin D3 metabolites on cell membranes may be related to changes in PA2 activity. The regulation is related to the stage of differentiation of the target cell population. Changes in fatty acid acylation and reacylation may be one mode of vitamin D3 action in cartilage. PMID- 1643115 TI - Diphosphorylation of platelet myosin ex vivo in the initial phase of activation by thrombin. AB - We prepared anti-platelet 20-kDa myosin light chain (MLC-20) antibody and demonstrated diphosphorylation of MLC-20 in platelets ex vivo in the initial phase of activation by thrombin. Our results are as follows. (1) By Western blotting, using anti-MLC-20 antibody, both mono- and diphosphorylated myosin were seen in the initial phase of aggregation of platelets by thrombin. The peak of the diphosphorylation was later than that of monophosphorylation and the degree of both mono- and diphosphorylation reduced in the process of aggregation. (2) ML 7 (a synthetic inhibitor of MLCK) inhibited both mono- and diphosphorylation of myosin and also blocked aggregation of thrombin-activated platelets. However, H-7 (an inhibitor of protein kinase C) had little effect on either the (di)phosphorylation of myosin or the aggregation of thrombin-activated platelets. (3) Arg-Gly-Asp-Ser (RGDS) peptide, a synthetic anti-adhesive peptide, inhibited aggregation of thrombin-activated platelets in a dose-dependent manner (100-200 microM). However, it had little effect on either mono- or diphosphorylation of myosin in the process of the platelet aggregation stimulated by thrombin. From these results, we conclude that mono- and diphosphorylation of myosin by MLCK play a role in the initial phase of activation of thrombin-stimulated platelets in vivo and that mono- and diphosphorylation of myosin by MLCK precedes the secondary signal mediated by GPIIb/IIIa. PMID- 1643116 TI - Pathways for arachidonic acid mobilization in zymosan-stimulated mouse peritoneal macrophages. AB - Resident peritoneal macrophages release arachidonic acid when challenged by zymosan, a phagocytosable particle. The present study was designed to investigate the pathways for arachidonic acid mobilization in zymosan-stimulated macrophages. Experiments were conducted with [3H]arachidonic acid-labeled macrophages to establish the relative contribution of acyltransferases, phospholipase A2, and diacylglycerol lipase to overall arachidonic acid release. Upon zymosan stimulation, [3H]arachidonic acid incorporation into phospholipids was significantly enhanced. Stimulus-induced activation of arachidonic acid incorporated was not observed immediately, but was found 5 min after cell challenge. On the other hand, the results indicated a rapid accumulation of intracellular free [3H]arachidonic acid that paralleled the appearance of both [3H]glycerol-labeled lysophosphatidylcholine and [3H]glycerol-labeled lysophosphatidylinositol, the by-products of phospholipase A2 action on phosphatidylcholine and phosphatidylinositol, respectively. A transient accumulation of [3H]arachidonate-carrying diacylglycerol was also observed. However, no appreciable alterations in the levels of [3H]monoacylglycerol were found. The phospholipase A2 inhibitor nordihydroguaiaretic acid substantially prevented the zymosan-induced arachidonic acid release. In contrast, RHC 80267, a diacylglycerol lipase inhibitor, though preventing diacylglycerol breakdown, did not have any effect on [3H]arachidonic acid release From these results, it is concluded that: (1) the phospholipase A2 pathway controls arachidonic acid release upon zymosan stimulation; (2) the diacylglycerol lipase pathway appears not to be involved in arachidonic acid release by stimulated cells; (3) the acyltransferases play a remarkable role in controlling free arachidonic acid levels, but they do not participate in the increase of free fatty acid levels observed upon cell stimulation. PMID- 1643117 TI - The activation of inactive membrane-associated protein kinase C is associated with DMSO-induced erythroleukemia cell differentiation. AB - The rapid redistribution of cytosolic protein kinase C (PKC) to membranes and its subsequent proteolytic activation to PKM have been implicated in the DMSO/HMBA induced differentiation of murine erythroleukemia (MEL) cells. However, DMSO was found not to induce detectable changes in PKC distribution in a MEL cell subline (MEL1) which differentiated normally in response to the agent. Nevertheless, the differentiation of MEL1 cells appeared dependent on an early PKC-related event because hemoglobinization was partially blocked by the PKC inhibitor H-7 added to cells within the first 2 h after DMSO induction. Indeed, a rapid (15-60 min) increase in membrane PKC activity was detected in DMSO-treated MEL1 cells using a novel method which quantitates the amount of 'active' PKC in intact membranes. This transient PKC increase resulted from the activation of 'inactive' enzyme already associated with membranes, and not from the translocation of cytosolic PKC. Conventional PKC assays cannot distinguish between active and inactive membrane PKC pools. DMSO also activated inactive membrane PKC in HL-60 cells, but not in S49T-lymphoma and WEHI-231 B-lymphoma cells which do not differentiate in response to DMSO. The results suggest that a rapid and transient increase in membrane PKC activity may be an important early step in DMSO-induced differentiation of erythroleukemia cells. PMID- 1643118 TI - Chick embryo heart cells with high and low intracellular calcium concentrations respond differently to ouabain. AB - In cell cultures of 10-day-old chick embryo hearts, we found two cell populations, one with high intracellular calcium concentration ([Ca2+]i) of 116 +/- 34 nM (S.E., high [Ca2+]i cells, n = 154) and another one with low [Ca2+]i of 46 +/- 14 nM [Ca2+]i (S.E., low [Ca2+]i cells, n = 171), as revealed by fura-2 digital imaging fluorescence microscopy. The proportion of the high [Ca2+]i cells varied as a function of the cell density from 10-60% of all cells. Histochemical staining of the cells showed that cells with high and low [Ca2+]i did not represent differences between muscle and non-muscle cells. When the cells were exposed to different concentrations of ouabain, the high [Ca2+]i cells showed a half maximal effect at 2.10(-9) M ouabain, but only a small increase in [Ca2+]i of 30%. The low [Ca2+]i cells reached their half maximal increase in [Ca2+]i at 4.10(-8) M ouabain. A second increase in [Ca2+]i in this cell type was observed between 10(-6) and 10(-5) M ouabain. Toxic concentrations of ouabain produced an excessive increase in [Ca2+]i in low [Ca2+]i cells, whereas high [Ca2+]i cells showed morphological degeneration due to their higher sensitivity to ouabain. In conclusion, we demonstrate that chick embryo heart contains cells with high and low [Ca2+]i which show differences in the sensitivity of their sodium pumps to cardiac glycosides. PMID- 1643119 TI - Report different results in esophageal perforation patients. PMID- 1643120 TI - Virginia's athletic exam form: results and revisions. AB - In followup of the expanded preparticipation physical exam form introduced by the Virginia High School League in 1989, the author finds substantial evidence of beneficial effects: 1) Perception by school administrators, parents, and students of distinctly improved physical evaluations. 2) Demonstration of previously unrecognized historical and physical findings of significance. 3) Newfound interest in the relationship of health, fitness, and sports among students, coaches, and physicians. 4) Recognition of Virginia's leadership in promoting safety among high school athletes. Suggestions from the medical community generated revisions in the form, which creates a more effective form and gives the physician more flexibility. PMID- 1643121 TI - Virginia's EMS-DNR Order: rules of usage. PMID- 1643122 TI - Virginia's advance medical directive. PMID- 1643124 TI - Screening children for lead poisoning: new guidelines. PMID- 1643123 TI - Severe hypoglycemia in diabetic pregnancy. AB - Our results are presented to reemphasize that strict glucose control in pregnant Type I diabetic patients carries not only significant benefits but risk as well. Despite careful attention, self glucose monitoring, multi-shot/pump insulin, diabetic team management and obstetrical expertise, pregnant Type I diabetic patients are at increased risk for hypoglycemic episodes. PMID- 1643125 TI - Ethics programs at community hospitals in Virginia. PMID- 1643126 TI - What kind of fiscal medicine are we practicing? PMID- 1643127 TI - The lost art. PMID- 1643128 TI - Dr. Blanton's moving word picture. PMID- 1643129 TI - [Evaluation of 5 methods for the diagnosis of infections by respiratory syncytial virus]. AB - BACKGROUND: To compare and evaluate four different rapid methods of respiratory syncytial virus antigen detection with the isolation of the virus in cell culture. METHOD: Ninety-eight nasopharyngeal swabs were studied, for respiratory syncytial virus isolation in Hep-2 cell line and for RSV antigen detection using direct immunofluorescence and three ELISA methods: Abbot RSV EIA (ELISA-1), RSV Antigen Detection System (ELISA-2) and Directigen RSV (Directigen). RESULTS: Of all 98 samples studied using the five mentioned methods, 42 (43%) were positive for respiratory syncytial virus. The most sensitive methods were ELISA-1 (82%) and immunofluorescence (82%). The most specific ones were direct immunofluorescence (86%) and Directigen (84%). The higher percentage of concordant positive results with respiratory syncytial virus culture were direct immunofluorescence (84%) and Directigen (82%). CONCLUSIONS: Rapid diagnostic methods for respiratory syncytial virus infection can not substitute the isolation method using cell line culture. We believe that respiratory syncytial virus isolation in cell culture combined direct with direct immunofluorescence or Directigen methods are the first choice diagnostic techniques for achieve a higher number of positive results in respiratory syncytial virus infected patients. PMID- 1643130 TI - [Hospital personnel who are nasal carriers of methicillin-resistant Staphylococcus aureus. Usefulness of treatment with mupirocin]. AB - BACKGROUND: The evaluation of health care workers role in methicillin-resistant Staphylococcus aureus outbreaks and the efficacy of mupirocin as a topical agent for nasal carriers. METHOD: Microbiologic study of nasal microflora of 1547 health care workers from the San Carlos University Hospital and 108 health care workers from related hospitals while an outbreak of methicillin-resistant Staphylococcus aureus nosocomial infections is in progress at San Carlos University Hospital. Assessment of the efficacy of mupirocin nasal ointment for nasal carriers using microbiologic controls of nasal and pharyngeal swabs at the end of treatment and two weeks after. RESULTS: In San Carlos University Hospital a total of 53 health care workers with nasal carriage of methicillin-resistant Staphylococcus aureus were found. That figure represents a 3.4% of all health care workers studied and also a 15.4% of methicillin-resistance among all S. aureus isolated. Among health care workers from related hospitals, only one nasal carrier was found. Forty-seven of all 53 methicillin-resistant Staphylococcus aureus isolated from San Carlos University Hospital health care workers and the strain isolated from the related hospitals health care worker were similar to the epidemic strain responsible for the outbreak. Mupirocin, as nasal ointment, was useful in eliminating nasal colonization in all cases. CONCLUSIONS: When a nosocomial outbreak of methicillin-resistant Staphylococcus aureus infections is detected, health care workers are one of the most important reservoirs. Topical treatment with mupirocin (nasal ointment) is useful for eliminating the nasal carrier status. PMID- 1643131 TI - [Rapid diagnosis of Chlamydia trachomatis using a DNA probe in a population with low risk of infection]. AB - BACKGROUND: To assess the efficacy of a newer diagnostic technique for Chlamydia trachomatis and its usefulness as screening method in populations at low-risk for Chlamydia trachomatis infection. METHODS: Open comparative trial between the EIA technique (Abbott Laboratories) and DNA gene probe (Gen Probe Diagnostic). A total of 1683 individuals (1630 women and 53 men) were screened with the two different techniques using samples obtained simultaneously. RESULTS: Among women, 66 give a positive result either by one or another technique. The prevalence was 4.04%. Sensitivity of DNA probe when compared with EIA assay was 64% and specificity was 98.9%. CONCLUSIONS: The DNA probe technique is faster than actual techniques and easy to do without major laboratory equipment. However, its price is high and its sensitivity poor in low-risk populations. PMID- 1643132 TI - [Diarrhea and eosinophilia in a Spanish man from Equatorial Guinea]. PMID- 1643133 TI - [Recurrent erythema and fever]. PMID- 1643134 TI - [Infection of an axillo-femoral vascular prosthesis by Candida albicans]. PMID- 1643135 TI - [Acute cholecystitis caused by Candida albicans]. PMID- 1643136 TI - [Tuberculous spondylitis caused by Mycobacterium bovis]. PMID- 1643137 TI - [Is bacteremia caused by Salmonella non-typhi an early complication in HIV infection?]. PMID- 1643138 TI - [Isolation of Moraxella catarrhalis in a case of postoperative mediastinitis]. PMID- 1643139 TI - [Disseminated actinomycosis and hepatic abscess caused by Arachnia propionica]. PMID- 1643140 TI - [Identification of diphtheroids in the laboratory: when and how]. PMID- 1643141 TI - [Hybridization techniques and mycobacteria. Evaluation in hospital practice]. AB - BACKGROUND: Commercially DNA probes procedure for identification of M. tuberculosis complex and M. avium complex isolates were evaluated, for accuracy and applicability, for use in the clinical laboratory. METHODS: Gen-Probe culture confirmation tests for M. tuberculosis complex and M. avium complex were performed on 94 mycobacterial isolates. RESULTS: Results were expressed as absolute percent hybridization, with values greater than or equal to 10% considered positive. The M. tuberculosis complex probes correctly identified 71 of 75 isolates, with 4 false-negative, for a sensitivity of 94.6% and a specificity of 100%. After repeat testing, all isolates were correctly identified, for a sensitivity of 100% and specificity of 100%. The M. avium complex probes correctly identified all M. avium-intracellulare isolates. There were no false-positives with 16 other mycobacteria. The mean percent hybridization (+/- the standard deviation) of M. tuberculosis complex isolates was 33.5 +/- 10.6; and for M. avium complex was 49.1 +/- 2.3. Among the isolates non M. tuberculosis and non M. avium complex, the percent hybridization range was 0.9 to 4.6. Overall, there were 4 discrepant M. tuberculosis results after repeat testing, being necessary to repeat it if the percent hybridization is between 10 and 5. CONCLUSIONS: GenProbe kits are highly sensitive and specific for use in identifying M. tuberculosis complex and M. avium complex isolates and will be useful in the clinical laboratory with a representative number of isolates. PMID- 1643142 TI - [Quantification of the levels of p24 antigen and antibodies in human immunodeficiency virus infection]. AB - BACKGROUND: Quantification and clinical evaluation of p24 antigen and anti-HIV antibody levels. METHODS: Follow up of 13 HIV infected patients (53 sera) by determination of p24 antigen, total anti-HIV antibodies, anti-p24 and anti-env antibodies by ELISA and their semiquantitation. IgG and IgM class antibody determination by immunoblot techniques. RESULTS: The highest levels of p24 have been found in WR 1 and WR 6 stages. Commonly accepted serologic pattern has not been found in 100% of our cases. Western-blot is more sensitive for the detection of anti-p24 antibodies. CONCLUSIONS: p24 antigen appearance and a decrease in anti-p24 antibody level is related to a worse clinical prognosis. p24 antigen quantification is a usefull test for monitoring AZT therapy in patients suffering from AIDS. PMID- 1643143 TI - [Meningitis in pediatrics. Clinical and epidemiological study of 173 cases]. AB - BACKGROUND: To know the incidence, clinical presentation, differential diagnosis and resistance level to antibiotics in pediatric meningitis. METHODS: 173 cases of meningitis (bacterial: 69, viral: 104) have been prospectively followed during 1988 according to a previously established clinical and laboratory protocol. RESULTS: Meningitis attack rate was 60 cases/100,000 children younger than 15 years per year (meningococcal: 25/100,000, Haemophilus: 2/100,000). Mortality was 1.4%. 40% of bacterial meningitis received previous antibiotic treatment. Sensitivity of culture, Gram stain, and direct antigen detection by latex and EIA was 79%, 61.7%, 20.5% and 34%, respectively. Bacterial and viral differential diagnosis, by the application of Boyer's score was 95% sensitive and 98% specific. Four out of six cases of Haemophilus meningitis were ampicillin and chloramphenicol resistant; 39% of meningococcus had their penicillin susceptibility decreased between 2 and 8 times, although no therapeutic failures were seen. CONCLUSIONS: Laboratory parameters might not separate bacterial and viral meningitis at early stages of illness. Gram stain is an excellent and sensitive method of bacterial detection in CSF. Moderate resistance to penicillin in meningococcus is very frequent but clinical failures are not yet present. PMID- 1643144 TI - [Antimicrobial resistance in strains of Salmonella enterica isolated in the Hospital de Basurto (Bilbao) from 1987 to 1990]. AB - BACKGROUND: Rate development of antimicrobial resistance of Salmonella strains in Hospital Basurto of Bilbao from 1987 to 1990 and to study their resistance mechanism. METHODS: The antimicrobial resistance for all strains isolated (1201 strains) was performed by means of a agar-diffusion test. We selected 32 multi resistant strains for additional study (MIC, conjugation, IEF, and plasmid profile). RESULTS: The most frequent isolated serotypes were S. enteritidis (79.01%), S. typhimurium (8.5%) and Salmonella serogroup C1 (6.9%). The resistance to one or more of 17 antimicrobial rose significantly: 9.6% in 1987; 10.25% in 1988; 16.45% in 1989 and 13.73% in 1990. The percentage of resistant serotypes were: S. typhimurium (40.2%); Salmonella serogroup B (31.8%); Salmonella serogroup C1 (16.8%); Salmonella serogroup D1 (13.04%); Salmonella serogroup C2 (9.09%) and S. enteritidis (8.4%). In 27 multi-resistant strains and their transconjugants, beta-lactamase bands with a pl: 5.4 and/or 5.6 compatible with TEM-1 and/or TEM-2 were observed. Also, these strains carried a plasmid of high molecular weight (125 MD). CONCLUSIONS: Although, the resistance of Salmonella is not a serious problem in our environment this situation is raising progressively with a greater number of strains with plasmid mediated beta lactamases. So, the antimicrobial policy will be more severe and righ in both hospital and extrahospital surrounding. PMID- 1643146 TI - Musings on the struggle--Part I: The "phonebook". PMID- 1643145 TI - [Cryptococcal meningitis and AIDS. Clinical description of 10 patients]. AB - We have studied 10 patients with cryptococcal meningitis and AIDS. Nine of them were intravenous drug users and four have been previously diagnosed of AIDS. In 60% of them cryptococcal meningitis was the first opportunistic infection, and as group represented only 6.3% of our 158 patients with AIDS on the same period. The most common symptoms were: malaise (100%), headache (80%), fever (60%), meningeal signs (50%). Two of them had focal neurological disease. CSF culture and serum cryptococcal antigen test were positive in 90%, the Indian ink in 77% and blood cultures in 30% of the cases, while indian ink preparation did it in 77%. MRI showed bilateral small lesions, deeply located, in 3 cases; it was also useful to prove optical tract lesions in a patient with blindness as a result of cryptococcal meningitis. We had treatment successes in 80% of the cases, all patients being treated with amphotericin B, alone in 4 and amphotericin B plus fluorocytosine in 6. Two patients died within the first 2 weeks. Maintenance therapy with fluconazole was effective and well tolerated, with 3 patients dying from causes other than cryptococcal meningitis. We recorded a survival rate over 12 months in 33% of patients. PMID- 1643147 TI - Gene transfer in vivo with DNA-liposome complexes: safety and acute toxicity in mice. AB - DNA can be introduced into a variety of cell types after formation of liposomal complexes with cationic lipids. In this report, conditions have been established to optimize the production of DNA-liposome complexes that efficiently transfect cells. The safety and toxicity of this method of gene delivery have been assessed after in vivo administration, either by intravenous or direct intratumor injection. Nine to eleven days after intravenous injection, DNA was found primarily in heart and lung tissue by PCR analysis. No abnormalities were evident from histologic examination of tissue, examination of tissue-specific serum enzymes, routine biochemical parameters, or electrocardiographic monitoring. DNA liposome complexes can therefore be used for the delivery of recombinant genes in vivo with minimal toxicity. PMID- 1643148 TI - The greatest rewards and the heaviest penalties. PMID- 1643149 TI - Resource needs for institutional programs in human gene therapy. PMID- 1643150 TI - Retroviral-mediated gene transfer of bone marrow cells during autologous bone marrow transplantation for acute leukemia. PMID- 1643151 TI - Phase I study of cellular adoptive immunotherapy using genetically modified CD8+ HIV-specific T cells for HIV seropositive patients undergoing allogeneic bone marrow transplant. The Fred Hutchinson Cancer Research Center and the University of Washington School of Medicine, Department of Medicine, Division of Oncology. PMID- 1643152 TI - Abstracts of the VIth Congress of the International Society for Peritoneal Dialysis. Thessaloniki, Greece, October 1-4, 1992. PMID- 1643153 TI - Thymidine kinase: a tumor marker with prognostic value for non-Hodgkin's lymphoma and a broad range of potential clinical applications. AB - Thymidine kinase (TK) is a cellular enzyme which is involved in a "salvage pathway" of DNA synthesis. It is activated in the G1/S phase of the cell cycle, and its activity has been shown to correlate with the proliferative activity of tumor cells. Additionally, certain viruses are able to induce cellular TK production and activity. Clinical studies have reported elevated serum TK levels in a variety of neoplasias. The majority of these studies concerned hematologic malignancies. TK seems to be a useful marker in non-Hodgkin's lymphoma, where it correlates with clinical staging and provides significant prognostic information on (progression-free) survival. Preliminary results in acute myeloid leukemia indicate that pretreatment serum TK values may predict the response to the first induction chemotherapy. Moreover, serum TK appears to have some clinical value in such solid tumors as prostate cancer, breast cancer, and small-cell lung cancer, whereas it is not a reliable marker of non-small-cell lung cancer and brain tumors. PMID- 1643154 TI - Differential expression of cell surface integrins on human mast cells and human basophils. AB - Integrins are multifunctional recognition molecules and are expressed on various hematopoietic cells. In the present study expression of integrins on the cell surface of human mast cells and human basophils was investigated by using monoclonal antibodies (mAbs) and indirect immunofluorescence. Human mast cells were obtained from lung (n = 5), uterus (n = 5) and skin (n = 4). Human blood basophils were obtained from normal donors (n = 2). In addition, HMC-1 cells (human mast cell line) and KU-812 cells (a basophil cell line) were analyzed. Primary mast cells were found to react with mAbs directed against the common beta chain of beta 1 integrins (CD 29), the alpha chain of VLA-4 (CD 49 d) and VLA-5 (CD 49 e), the beta chain of beta 3 integrins (CD 61), and the alpha chain of the vitronectin receptor (VNR) (CD 51). Mast cells were not recognized by mAbs to beta 2 integrins (CD 18, CD 11 a, CD 11 b, CD 11 c), the alpha chain of VLA-2 (CD 49 b), and VLA-6 (CD 49 f). No differences in expression of integrins on human mast cells obtained from different organs were found. HMC-1 cells and primary mast cells expressed an almost identical pattern of integrins. Human basophils and KU-812 cells were found to react with mAbs directed against beta 1-integrins (CD 29, CD 49 b, CD 49 d, CD 49 e) and beta 2-integrins (CD 18, CD 11 a, CD 11 b, CD 11 c). Together, mast cells and blood basophils express a unique pattern of integrins. These cell surface structures may be involved in the distribution of basophils and tissue mast cells and their accumulation and function in inflammed tissues. PMID- 1643156 TI - Effects of a preformed extracellular matrix on long-term serum-free bone marrow culture. AB - The extracellular matrix (ECM) produced by the stromal layer plays a key role in the regulation of commitment and differentiation of hematopoietic cells. Long term bone marrow culture (LTBMC) allows analysis of the stromal microenvironment. Recently, serum-free LTBMC has been described, but the formation of a classical adherent layer was never observed under these conditions. We have evaluated the effect(s) of a chemically well defined ECM on serum-free and serum-dependent LTBMC. In serum-dependent cultures ECM did not induce a significant increase of hematopoiesis. In serum-free conditions, a marked improvement of hematopoiesis was observed, both in terms of CFU-GM and BFU-E yield and in duration of cultures. A confluent stromal layer was observed only in the presence of ECM. The present results indicate that the addition of ECM to serum-free cultures provides a standardized culture condition, while improving progenitor cell recovery and allowing formation of a confluent stromal layer. Moreover, ECM+LTBMC may provide a model to study the effect(s) of adhesive proteins and hematopoietic growth factors normally present in serum. PMID- 1643155 TI - Ph-negative and bcr-negative atypical chronic myelogenous leukemia: biological features and clinical outcome. AB - We report the clinical, hematologic, cytogenetic, and molecular characteristics of 13 patients with Philadelphia-negative (Ph-), bcr-negative atypical chronic myelogenous leukemia (CML). In the majority of cases, the phenotypic features at presentation resembled those of typical CML. However, these patients presented with a higher median age, lower median hemoglobin levels, and lower leukocyte and platelet counts than patients with Ph-positive CML. Cytogenetic analysis showed an abnormal karyotype in only one case. Southern blot investigation, using probes exploring the entire M-bcr region, demonstrated the absence of genomic bcr-abl rearrangements. The assessment of clonality in five patients (study of X methylation patterns in females heterozygous at the DXS255 locus) indicated the proliferation of a monoclonal cell population. Disease evolution was mostly characterized by bone marrow failure, extramedullary infiltrates, and poor response to chemotherapy, without evidence of overt acute transformation. Our observations suggest that some hematologic and clinical features and the modalities of disease progression are presently the most helpful factors in distinguishing these bcr/abl-negative patients from those with typical bcr+CML. The differences existing also with chronic myelomonocytic leukemia (CMMoL), allow the consideration of ph-/bcr- CML as a separate entity, the nature of which remains to be elucidated. PMID- 1643157 TI - Increase in Ara-C sensitivity in Ara-C sensitive and -resistant leukemia by stimulation of the salvage and inhibition of the de novo pathway. AB - In this study the hypothesis that inhibition of the de novo pathway results in stimulation of salvage pathway activity was tested. The key enzyme in the balance between these two pathways is ribonucleotide reductase (RR), which can be inhibited by hydroxyurea (HU). The metabolism of 1-beta-D arabinofuranosylcytosine and 5-Aza-2 deoxycytidine (Aza-dC), which are activated via the salvage pathway, was evaluated in cells from Ara-C-sensitive and resistant myelocytic leukemia cell line (BNML-Cl/0 and BNML-Cl/Ara-C). The combination of HU and Ara-C caused as much as a threefold increase of Ara-CTP; it significantly increased the incorporation of Ara-C into DNA and induced synergistic cytotoxicity, as evaluated in a colony assay. Even in the deoxycytidine (CdR) kinase-deficient Ara-C-resistant cell line, HU was partially able to restore sensitivity to Ara-C and Aza-dC. dCTP levels are reduced during the first 10 h after incubation with HU, but this effect vanishes at the time when phosphorylation is maximal. Increased CdR kinase activity in cell-free extracts could explain the enhanced synthetic salvage pathway activity, which is likely due to the fact that more enzyme is present (Vmax has increased by Km unchanged). RR inhibition combined with Ara-C might provide a means of eliminating leukemic cells with suboptimal anabolic salvage pathway activity, which otherwise survive Ara-C chemotherapy. PMID- 1643158 TI - Cyclosporin A in aplastic anemia--report of a workshop. AB - The management of aplastic anemia continues to challenge clinical investigators. With bone marrow transplantation or immunosuppression the prognosis of the patient with aplastic anemia has improved remarkably. For patients who are not eligible for bone marrow transplantation, antilymphocyte globulin has become the standard treatment. There is growing evidence that some patients also respond to immunosuppression with cyclosporin A. Further data suggest that combination of cyclosporin A with antilymphocyte globulin or androgens might be beneficial. An international workshop summarized the data on cyclosporin A treatment in aplastic anemia and attempted to create guidelines for the use of cyclosporin A in the management of aplastic anemia. PMID- 1643159 TI - A monoclonal antibody-linked immunoassay for hemoglobin H disease. AB - A murine monoclonal antibody (mAb) was generated that recognizes hemoglobin (Hb) H, the tetrameric form (beta 4) of human beta-globin chains. The antibody beta 4 1 (gamma 1, kappa) does not react with Hbs A, F, Bart's, or isolated beta chains, indicating that the antibody recognizes an epitope comprised of multiple beta chains. A simple, rapid, and sensitive enzyme immunoassay was established to detect and quantitate Hb H in hemolysates from subjects with Hb H disease. The delta globin level in these patients was also measured using the monoclonal antibody delta-1, which is specific for delta chains of Hb A2. With these assays, 20 hemolysates from subjects with Hb H disease' ten from normal adults and ten from newborn babies were analyzed. The percent of Hb H ranged from 1.5% to 25% in Hb H patients. There was a significant average reduction (32%) in delta chains in these samples as compared with the normal average adult value. The decreased expression of alpha chains thus results in a reduction of the levels of normal Hbs A and A2 and accumulation of beta 4, causing Hb H disease. PMID- 1643160 TI - Anti-phospholipid antibodies bind to platelet microparticles in idiopathic (autoimmune) thrombocytopenic purpura. AB - We recently reported that IgM antibody-related microparticles exist in some patients with idiopathic thrombocytopenic purpura (ITP) [14]. In this study, we investigated the relationship between antiphospholipid (cardiolipin and phosphatidylinositol) antibodies and microparticles in 56 ITP patients. We used an ELISA to detect anti-phospholipid antibodies. IgG antibodies against cardiolipin and phosphatidylinositol were detected in 13 and 12 patients, respectively. The titers of IgG antibodies against these phospholipids did not correlate with the platelet-associated IgG level or the platelet count. Next, we investigated the binding of anti-phospholipid antibodies to platelets and microparticles. Microparticles were obtained by incubating washed platelets with collagen plus thrombin. ITP plasma containing IgG-class anti-phospholipid antibodies showed significantly increase binding to microparticles compared with plasma without such antibodies (p less than 0.001). Our results suggest that anti phospholipid antibodies could affect the function of platelet microparticles in ITP. PMID- 1643161 TI - TNF induces cytoplasmic vesicles in actinomycin D-treated K 562 cells. AB - We report here that tumor necrosis factor alpha (TNF) induces peculiar cytoplasmic vesicles in the human erythromyeloid leukemia cell line K 562, sensitized to the cytotoxic action of TNF by a treatment with the inhibitor of transcription actinomycin D. These vesicles are well delineated ultrastructurally. The formation of these vesicles is characteristic for the combination of actinomycin D with TNF and precedes the changes of apoptosis and cellular disintegration. These vesicles correspond to an intermediate step in the cytotoxicity caused by TNF and may indicate that reactive metabolites are involved in the mechanism of action of TNF. PMID- 1643162 TI - Lymph node histology simulating T-cell lymphoma in adult-onset Still's disease. AB - A patient with adult-onset Still's disease (AOSD) underwent lymph node biopsy as part of initial evaluation for fever of unknown origin. The lymph node histology showed a massive, diffuse immunoblastic hyperplasia, simulating T-cell lymphoma. This nodal histology differs from rheumatoid arthritis, where mostly a follicular B-cell reaction predominates. Evaluating fever of unknown origin when one is unacquainted with this massive immunoblastic hyperplasia can lead to the wrong diagnosis of T-cell lymphoma in patients with AOSD. PMID- 1643164 TI - Reversible bone marrow aplasia induced by naproxen. AB - We report a case of reversible bone marrow aplasia related to the use of naproxen. A 71-year-old women developed severe pancytopenia after she had been treated with naproxen for more than 8 weeks. Bone marrow examination showed marked hypocellularity compatible with aplastic anemia. Full recovery of the pancytopenia and bone marrow was observed when naproxen was discontinued. Absence of exposure to other drugs and lack of underlying disorders known to cause bone marrow aplasia makes this case unique. PMID- 1643163 TI - Sweet's syndrome as the presenting symptom of hairy cell leukemia with concomitant infection by Mycobacterium kansasii. AB - A patient with Sweet's syndrome and leukopenia is reported. Hematological evaluation revealed hairy cell leukemia (HCL). The clinical picture was dominated by persistent fever, which is a common feature of both Sweet's syndrome and HCL. Since fever frequently reflects concomitant infection in HCL, a thorough search for infectious disease was performed. Blood cultures grew Mycobacterium kansasii. The patient recovered after treatment with recombinant interferon-alpha (r-IFN alpha) and tuberculostatic drugs. Remarkably, the skin lesions completely regressed within 1 week after the start of r-IFN-alpha. In the literature, Sweet's syndrome is rarely mentioned as a feature of HCL. Mycobacterial disease, especially atypical mycobacteria, is relatively often seen in HCL. PMID- 1643165 TI - Immunohistochemical and histopathological study of experimental rabies infection in mice. AB - An immunohistochemical and histopathological study using the ABC technique was carried out to examine time-sequential virus spread in the central nervous system (CNS) of mice after inoculation with the CVS strain of fixed rabies virus by different routes; intracerebral (ic), intraocular (io), intranasal (in), intramuscular (im) and subcutaneous (sc). Only the ic and io inoculations caused fatal infections, so that detailed analysis was conducted on mice inoculated by these two routes. In ic-inoculated mice, viral antigens were detected mainly in neurons in the cerebral cortex and in the pyramidal cells and granular cells of the hippocampus. After io inoculation, viral antigen was first detected in the trigeminal nerve ganglia, following which it spreads to the cerebral cortex and cerebellum. In the hippocampus only a few cells were viral antigen-positive at the early stage after io inoculation. There were no inflammatory lesions or Negri bodies in the CNS of mice infected by either route. This suggests that clinical signs such as ataxia or depression leading to death may be due to the direct effect of the virus on the functions of neural cells, but not to inflammatory reactions. The ABC method will be useful for the early diagnosis of suspected patients or animals to have the disease when conventional histopathological and immunofluorescent antibody techniques can not detect lesions or viral antigens. PMID- 1643166 TI - Relationship between halftime for sulfobromophthalein clearance and post-surgical prognosis in cows with abomasal displacement. AB - In 47 dairy cows with abomasal displacement, 34 (72%) cows were confirmed to have the lipid infiltration in liver by biopsy examinations. The pathological degree of the lipid infiltration was significantly higher in the cows with left abomasal displacement than in those with right one. The halftime for sulfobromophthalein clearance (BSP-T1/2) was markedly increased in nonrecovered cows with left abomasal displacement. In left abomasal displacement cases, cows with the T1/2 less than 11 min recovered regardless of the degree of liver lipid infiltration, but those with the T1/2 longer than 11 min showed a significantly lower recovery rate (44%). Therefore, it was concluded that the BSP-T1/2 was one of valuable parameters for predicting the prognosis of this disease. PMID- 1643167 TI - Equine haptoglobin: isolation, characterization, and the effects of ageing, delivery and inflammation on its serum concentration. AB - Haptoglobin (Hp) was isolated from equine serum by ammonium sulphate precipitation, anion-exchange chromatography and gel filtration. Equine Hp which migrated to the alpha 2-globulin region in electrophoresis, contained 2 fractions with molecular weights (NW) of 108,000 and 105,000, and each fraction consisting of 2 subunits. Quantitative measurement of Hp in equine serum was performed by the single radial immunodiffusion method using anti-equine Hp serum. In clinically normal horses, the highest concentration of serum Hp was found in newborn foals and a high value was maintained until 12 months of age. The concentration then decreased with age. Normal Hp values were 5.25 +/- 2.36 mg/ml in foals (less than or equal to 12 months old), 2.19 +/- 1.54 mg/ml in adult horses (greater than or equal to 18 months old) and 3.62 +/- 0.81 mg/ml in all horses. Serum Hp concentration in mares during the perinatal period in comparison with the normal adult female was high for 4 months pre-partum, a passing increase at delivery, and then decreased at 2 weeks post-partum returning to normal within 1 month of delivery. In horses with experimentally-induced inflammation, serum Hp concentration began to increase immediately after treatment and reached the highest value, 1.5 to 9 times higher than those of pre-treatment at 2 to 5 days, then decreased within 4 weeks. It was also elevated in most cases of horses with clinically inflammatory signs. PMID- 1643168 TI - Production of the vacuolation factor of Bacillus cereus isolated from vomiting type food poisoning. AB - Vacuole response in HEp-2 cells was induced with culture supernatants of Bacillus cereus strains isolated from outbreaks of vomiting- and diarrheal-type food poisoning grown in rice flour and laboratory media. High vacuole response was obtained with culture supernatants of B. cereus strains isolated from vomiting type food poisoning grown in cooked rice suspension or on a cooked rice plate, whereas no response was obtained with those of the same strains grown in brain heart infusion and trypto-soya broth media. The vacuole activity appeared only after spore formation of B. cereus. The activity was stable to proteolytic enzymes, heating, and exposing to pH 2.0 and 11.0. Of 124 strains isolated from B. cereus food poisoning that were tested, the vacuole activity was observed by 68 of 110 (61.8%) of the strains isolated from the vomiting-type food poisoning but not by all strains (14 strains) from diarrheal-type ones. Moreover, the vacuole response in the HEp-2 cells was found to be induced by 56 of 76 (73.7%) of the serotype H-1 strains isolated from vomiting-type food poisoning. PMID- 1643169 TI - Morphological changes of epiphyseal plate in the long bone of chondrodysplastic dwarfism in Japanese brown cattle. AB - A total of 20 cases of disproportionate calves on Japanese Brown cattle were examined morphologically. Investigation of 5 affected calves revealed that the insufficiency of endochondral ossification was confined only to the long bones of the limbs and was not accompanied by other associated changes. On the basis of the histological changes of epiphyseal plate and the affected site, this condition may be called chondrodysplasia of the rhizomelic type. Therefore, this disorder was defined as a bovine dwarfism. From three dimensional image analysis and histological changes of the tibial proximal portion in the other 15 cases, deformity and shortness of the tibia were related to the state of distribution and the degree of damages of the epiphyseal plate. In the affected cartilage matrix, cystoid degeneration, fibrous striation, bone spicule, necrotic foci and rent were found. Inadequate metachromasia suggests the abnormal staining of sulfated glycosaminoglycans and alcian blue stainability may be attributable to the abnormal interactions between proteoglycan and other matrix components. At the interface of cartilage and bone, irregular calcification, fibrotic scar and sealing by osseous tissue with relation to vascularity were found. These changes in this study indicated the failure of modeling on the epiphyseal plate, showing disturbance of chondrocytic differentiation and abnormal formation of the matrix. PMID- 1643170 TI - Prevalence of Listeria (spp.) in wild rats captured in the Kanto area of Japan. AB - In the Kanto area a total of 245 wild rats were captured. All rats captured in Ikebukuro (110 rats) and 9 out of 41 rats in Yokohama were Rattus rattus, and all other 126 rats were Rattus norvegicus. In Kashima and Ikebukuro, listeria was isolated from 28 rats (77.8%) and 27 rats (24.5%), respectively, but in the other 4 areas listeria was isolated from 0-7% rats. Listeria monocytogenes was isolated from 12 rats (10.9%) captured in Ikebukuro and 2 rats in Kashima and Numazu. The frequent isolation of L. monocytogenes in buildings suggests the possibility of R. rattus as a reservoir of L. monocytogenes and the continual environmental contamination in buildings by L. monocytogenes. PMID- 1643171 TI - Activation of bovine peripheral blood monocyte and its suppressive effect on parasitemia in Theileria sergenti infected calves. AB - Activation of bovine peripheral blood monocytes and its suppressive effect on parasite growth was examined in Theileria sergenti-infected calves by using a rosette assay that detects changes in Fc receptor expression and by luminol dependent chemiluminescence response. Monocyte activation preceded the peak of parasitemia but was depressed parallelly with the growth of the parasites. When four calves were treated with prednisolone, three showed a good correlation between the suppression of monocyte activity and an increase of parasitemia. PMID- 1643172 TI - Cardiac musculature of the cranial and caudal venae cavae and the pulmonary vein in the fowl. AB - The cardiac musculature of cranial and caudal venae cavae and pulmonary vein was examined to clarify its distribution pattern in the fowl using both light and electron microscopies. The musculature was distributed from the heart to the root of subclavian vein in the cranial vena cava, to the cranial margin of the liver in the caudal vena cava, and to the left and right distal pulmonary veins in the pulmonary vein, respectively. Judging from the morphology and distribution pattern in the venous wall, the cardiac musculature in the fowl is thought to share the same phylogenic origin with that in mammals. The ultrastructure of cardiac myocytes including transitional cells in the cranial vena cava and the pulmonary vein resembled that of atrial myocytes. While, the typical specialized myocytes such as Purkinje fiber were found in the caudal vena cava of the fowl. PMID- 1643173 TI - Disseminated mycoses in cattle. A study on nine autopsy cases. AB - Nine cases affected with disseminated mucormycosis (1.3% of all autopsy cases and 20.0% of systemic mycosis) were found among bovine systemic mycosis examined from 1975 to 1985. The disseminated lesions were found in the lungs (3 cattle), heart (2 cattle), liver (2 cattle), spleen (1 beef cattle), kidneys (1 cattle), central nervous system (1 cattle) and lymph node (1 cattle). Histological examination revealed granulomatous lesions, necrotic foci including infarcts, and thromboangiitis with the hyphae of a member of the Zygomycetes and neutrophil reaction. Granulomatous lesions with asteroid bodies were found in the liver. Metastatic foci were established from the primary lesions found in the alimentary organ (4 from the forestomach or abomasum and 1 from the tongue). One case resulted from uterine mucormycosis, and no primary lesion was found in the other 3 cattle. Complicated infection with respiratory aspergillosis occurred in 4 cases with alimentary mucormycosis. All of the 9 cattle had predisposing disorders. Six cattle had been manifested with prolonged debilitating conditions. Anemia was present in 4, leukopenia in 2 and lymphopenia in 1 cattle. PMID- 1643174 TI - Immunohistochemical observations on pneumonic lesions caused by Rhodococcus equi in foals. AB - An immunohistochemical analysis of Rhodococcus equi-induced pneumonia in 10 foals was performed by biotin-streptavidin system. The detection of R. equi was more sensitive in immuno-stain using anti-R. equi serum than in Gram's stain. This bacteria also reacted to anti-BCG serum. Lysozyme and alpha 1-antitrypsin were detectable in macrophages. A particularly intense staining was observed in association with intracellular bacteria. Though a degree of reaction for alpha 1 antichymotrypsin was very low in comparison with lysozyme and alpha 1 antitrypsin, it was also demonstrated in macrophages ingesting R. equi. These bacteria were almost intact under an electron microscope. Therefore, the surface components of R. equi may play important roles of protection from intracellular enzymes of macrophages. The cells containing intracytoplasmic IgM, IgG or IgA were a few in number and scattered predominantly around the pneumonic lesion. It is considered that the bactericidal activity by immunoglobulins may be weak in comparison with phagocytosis by macrophages. PMID- 1643175 TI - Comparison of the distribution of carbonic anhydrase isozymes (CA-I, CA-II, CA III) in the rat gastrointestinal tract. AB - The present paper described the immunohistochemical distributions of carbonic anhydrase (CA) isozymes. CA-I, CA-II and CA-III, in the epithelium lining the rat gastrointestinal tract, with rabbit antibodies to equine CA-I, CA-II and CA-III. Prior to the immunohistochemical examinations, the crossreactivities of these antibodies to the rat-antigens were confirmed in this study. In the stomach, surface epithelial cells and parietal cells of the glandular region showed an immunoreactivity only to CA-II. In the large intestine, each immunoreactivity to CA isozyme (CA-I, CA-II and CA-III) was localized in the upper portion of intestinal glands, and decreased toward the distal digestive tract, but absent in the small intestine. The present histological findings suggested that the CA isozymes might play a role in the ion-transportation during the water absorption in the rat large intestine. PMID- 1643176 TI - Annual changes of testis size, seminiferous tubules and plasma testosterone concentration of wild Sika deer (Cervus nippon yesoensis Heude, 1884) in Hokkaido. AB - Testis size, seminiferous tubules and plasma testosterone concentrations showed conspicuous annual changes in Sika deer of Hokkaido, Japan. The onset of the spermatogenic process occurred in July or August. Spermatogenic activity had already reached its height in late October, at the beginning of the rutting season, and had begun to decline in late December. Spermatogenesis had stopped in February or March. Plasma testosterone concentrations showed very high levels in late October and early November, but was almost at the basal level in February, March, June and December. The wide individual variation of the plasma levels in October suggest pulsatile secretions of testosterone. PMID- 1643177 TI - An improved method for extraction and cleanup of aflatoxin B1 from liver. PMID- 1643178 TI - Unilateral optic nerve aplasia in an F344 rat with special reference to pathomorphological changes of the optic nerve pathways. PMID- 1643179 TI - Bovine cases of urolithiasis treated with traditional herbal medicine, P-3. PMID- 1643180 TI - Glucose utilization in cats, dogs and cows measured by euglycemic insulin clamp technique. PMID- 1643181 TI - Whole-mount preparation of renin-containing cells in hydronephrotic mice. PMID- 1643182 TI - Fc receptor expression and immune phagocytosis in chicken monocytic cell lines. PMID- 1643183 TI - Effect of proteolytic enzyme on experimental infection of mice with Pseudomonas aeruginosa. PMID- 1643184 TI - An occurrence of vitamin A deficiency in chickens in Zambia. PMID- 1643185 TI - Inhibition of germinal vesicle breakdown of isolated cumulus-free mouse oocytes in culture by a calcium inhibitor, TMB-8. PMID- 1643186 TI - Fine structure of spreading hemocytes of an estuarine gastropod mollusc, Clithon retropictus. PMID- 1643187 TI - Recent advances in the growth and isolation of primitive human haemopoietic progenitor cells. PMID- 1643188 TI - N-methylformamide effects on cell proliferation and antigenic pattern in HT-29 colon carcinoma cell line. AB - The effects of the differentiating agent N-methylformamide (NMF) on cell proliferation and antigenic pattern of HT-29 colon carcinoma cells have been investigated. The cell line was cultured in the presence, or absence, of 1% NMF and tested for the above mentioned characteristics, both in vitro and after injection into nude mice. The percentage of cells in the various cell cycle compartments was estimated by flow cytometry. The presentation on the cell surface of molecules such as tumour associated antigens (TAAs), HLA class I molecules and epidermal growth factor receptor (EGF-R) was analysed by ELISA, flow cytometry and immunohistochemistry. Results demonstrate that NMF impairs HT 29 cell proliferation with a remarkable accumulation in the G0/G1 phases, as well as inducing a modification of the membrane antigenic pattern. The presence of NMF in the culture medium decreases the TAAs and EGF-R whereas HLA antigen maintains the same level of positivity in the two cell lines. These alterations are consistent with a different behaviour in vivo of the tumours originated from NMF treated and untreated cells. Tumours derived from NMF treated cells show a delay in the appearance and low levels of immunodetectable carcinoembryonic antigen (CEA) molecules. PMID- 1643189 TI - Nuclear and chromosomal replication patterns in chorionic villi cells by bromodeoxyuridine labelling and DNA flow cytometry. AB - Cell kinetics of chorionic villi (CV) were studied by BrdUrd-incorporation detected by fluorescence-plus-Giemsa and BrdUrd-antibody techniques, and by DNA flow cytometry. Growth characteristics of long-term cultures of CV resembled fibroblasts with a total cell cycle time of 26 h, final S phase of 9 h, penultimate S phase of 16 h and G2/M phase of 3-4 h. Especially useful for a quick routine diagnostic approach, Ultroser RG, a commercially available serum supplement, significantly increased cell proliferation and stabilized cell cycle lengths to a total cell cycle time of 14 h, final S phase of 7 h, penultimate S phase of 6 h and G2/M phase of 4 h. Moreover, mitotic activity steadily increased in cultured CV, when studying six successive subculturings. This reflects adaptation to the culture conditions rather than an inherent response of cultured CV cells of increasing passage numbers. Native villi exposed to BrdUrd immediately after biopsy show lower rates of uptake than do aliquots after overnight incubation. As shown by BrdUrd-pulse labelling studies, more than 7 h are required to overcome the proposed 'biopsy stress'. This correlates with routine diagnostic techniques, in which many more metaphase cells are observed in short-term cultures than in direct preparations. PMID- 1643190 TI - Plasma cell proliferation in the chicken harderian gland. AB - Studies to examine the percentages of proliferating plasma cells (PPC) in the Harderian gland (HG) were carried out in chicks between 5 and 12 weeks of age. Two methods, 5-bromo-2'-deoxyuridine (BrdUrd) incorporation into DNA and flow cytometric analysis of propidium iodide (PI) stained cells, were employed in control and emetine dihydrochloride treated birds. Flow cytometric analysis of PI stained cells showed the percentages of plasma cells in S phase were highest between 6 and 8 weeks of age. After this period of time, the number of S phase plasma cells decreased and remained low through 12 weeks of age. The lowest percentages of plasma cells in G0 + G1 were found at 6 and 8 weeks of age, and all ages had equal percentages of plasma cells in G2 + M phase. After administration of the protein synthesis inhibitor emetine dihydrochloride a common pattern of plasma cell depletion and repopulation in the HG was observed. At 3 and 5 days post-treatment the plasma cell population in the gland decreased and by 7 days post-treatment repopulation of the gland with plasma cells had taken place. Anti-BrdUrd staining of frozen sections revealed that the number of PPC were decreased at 3 days after emetine treatment but were as high as, or higher than, controls at 5 and 7 days post-treatment. Flow cytometric analysis indicated that some birds were more severely affected by emetine. Namely, the percentages of plasma cells in S phase were lower at 3 and 5 days post-treatment. Even though most birds were severely affected by emetine treatment during the experiments, they possessed a cell population with the proliferative capacity to quickly repopulate the HG by 7 days post-emetine treatment. PMID- 1643191 TI - Chromosomal influence on hybrid cell proliferation. AB - When normal cells and cancer cells (usually from the same species) are experimentally fused the resultant hybrid cells show loss of the tumorigenic phenotype. To examine the phenotypic phenomenon of growth suppression in hybrid cells in vitro, we examined the doubling times of somatic cell hybrids which contained single or multiple chromosomes derived from another species (inter species hybrids). In all of the hybrid lines examined, the presence of transferred chromosomes prolonged the cell population doubling times in proportion to the number of such chromosomes found in the hybrid lines. These findings provide additional evidence to support the hypothesis that increasing the genetic burden of cells may reduce the division potential of cells cultured in vitro. PMID- 1643192 TI - Sensory gating in rats depleted of dopamine as neonates: potential relevance to findings in schizophrenic patients. AB - Based on a recent hypothesis of reduced subcortical dopaminergic tone, evidence of early neurodevelopmental deviation, and acoustic startle abnormalities in schizophrenia, we examined acoustic startle in adult animals depleted of dopamine (DA) as neonates. Male rat pups received intracerebroventricular injections of either 6-hydroxydopamine (6-OHDA, 100 micrograms) or its vehicle on postnatal day 3. At 60 days of age, baseline startle and prepulse inhibition (PPI) of startle were assessed in a no injection condition, with all other animals receiving injections of saline or the DA agonist, apomorphine. Acoustic startle was elicited using 120 db white noise bursts alone or preceded by prepulses of 75, 80, and 85 db. Animals treated with 6-OHDA exhibited a 93% depletion of striatal DA compared to vehicle-treated controls. Whereas DA depleted animals did not differ from controls in the no injection condition, they showed greater baseline startle and reduced PPI compared to controls after saline injections. Depleted animals also showed exaggerated responses to apomorphine, with greater increases in baseline startle, loss of habituation, and decreased PPI compared to controls. Findings indicate that neonatal DA depletions lead to increased baseline startle and impaired sensory gating in adulthood after saline injections and dopamine agonists compared to controls. These findings may be relevant to a subgroup of psychotic patients that exhibit similar startle abnormalities as well as signs of hypodopaminergic function. PMID- 1643193 TI - Variability of TRH test responses in depressed and normal elderly subjects. AB - Thyrotropin releasing hormone (TRH) tests were conducted in 33 elderly patients with Major Depressive Disorder and 99 normal elderly volunteers. A wide range of thyrotropin-stimulating hormone (TSH) responses to TRH injection was revealed. A gender effect was found such that men had significantly diminished TSH responses to TRH relative to women (p = 0.008). However, there were no significant differences noted between depressed patients and normal elderly subjects of either gender. It appears that the wide range of TSH responses to TRH found in normal elderly men and women blurs any measurable differentiation between depressed patients and normal subjects and thereby limits the usefulness of the TRH test in the study of depressive disorder in elderly patients. PMID- 1643194 TI - Neural development is regulated by classical neurotransmitters: dopamine D2 receptor stimulation enhances neurite outgrowth. AB - The classical neurotransmitters serotonin and dopamine are thought to be involved in the etiology or treatment of a variety of psychiatric disorders. Recent studies suggest that these neurotransmitters may also have roles as neural morphogens during brain development. Previously, we have demonstrated that stimulation of serotonin 5-HT1A receptors selectively inhibited neurite branching in an in vitro system (Sikich et al 1990). In the present study, the developmental role of dopamine D2 receptors in the control of neurite outgrowth has been investigated by quantitating the morphological response of cortical neurons to agonist stimulation in vitro. Cultures of fetal rat frontal, cortical neurons were shown to express both alternatively spliced forms of D2 receptor messenger RNA (mRNA). The larger mRNA form predominated (D2A444:D2A415 ratio of about 6:1). In a small but significant percentage of these neurons, culture in the presence of the D2 receptor selective agonist, quinpirole, resulted in a three-to ten-fold increase in the length of neurites and in the number of branch points per neurite. These effects were blocked by the D2 receptor antagonists eticlopride and spiperone. Early abnormalities in the stimulation of dopamine or serotonin receptor subtypes could lead to the types of neuroanatomical changes observed in studies of schizophrenia, bipolar affective disorder, and autism. These morphogenic effects of classical transmitters could unite neurodevelopmental and neurotransmitter theories of the etiology of severe psychiatric disorders. PMID- 1643195 TI - Behavioral response to diazepam in a residential laboratory. AB - Two groups of three healthy adult male volunteers without histories of sedative or other drug abuse participated in 15-day residential studies. Each day consisted of a private work period (10 AM to 4:30 PM), during which subjects participated in traditional laboratory performance tasks, and a social period (5 to 11:30 PM), during which subjects had access to recreational activities available under social or private conditions. Tobacco cigarettes and food were available throughout each day (9 AM to 12 PM). Diazepam (5 or 10 mg/70 kg) or placebo was administered orally twice daily in alternating three-consecutive-day intervals. Dosing order varied between groups. Diazepam had no effect on the total amount of time subjects spent in social conditions; however, the low dose increased verbal interaction, while the high dose decreased verbal interaction. Both doses disrupted performance on a second-order repeated-acquisition task but produced no effects on the other performance measures. Five of six subjects increased caloric intake following at least one dose, with the largest increases observed in subjects with the lowest baseline intake. Increases in subject reports of dose "Potency" and "Sedated" were also observed following the high dose. Diazepam doses routinely used in clinical settings influenced a variety of behaviors that are observed in the natural ecology, but not performance on accepted laboratory tasks. PMID- 1643196 TI - The interaction of motor, memory, and emotional dysfunction in Wilson's disease. AB - Measures of the degree of motor, psychiatric, and declarative memory disability were made in neurologically impaired and neurologically asymptomatic patients with Wilson's disease. All three types of disability were significantly greater in the neurologically impaired than in the asymptomatic patients. There was no significant interaction between these disabilities in the impaired patients suggesting that motor, psychiatric, and memory symptoms are three relatively independent sequelae of the copper-induced central nervous system (CNS) damage that underlies Wilson's disease. PMID- 1643197 TI - The effects of nicotine plus haloperidol compared to nicotine only and placebo nicotine only in reducing tic severity and frequency in Tourette's disorder. AB - We studied the effects of chewing nicotine gum on tic frequency and severity in 10 patients with Tourette's disorder (TD) on haloperidol, versus 9 untreated TD patients; placebo gum was administered to 5 of these untreated patients. Videotapes of patients during a 2-hr period of 30 min baseline, 30 min gum chewing, and two 30-min postgum-chewing periods were utilized. For those TD patients on haloperidol, significant reductions occurred in tic frequency and severity during the gum-chewing and the two postgum-chewing periods. Nicotine gum alone caused a decrease in tic frequency only during gum-chewing and one postgum chewing period, while placebo gum showed no effect. In this study, nicotine markedly potentiated haloperidol effects in treating TD, and showed lesser effects on TD when used alone. PMID- 1643198 TI - Season of birth and electrodermal activity in functional psychoses. AB - The present study examined the association between electrodermal activity (EDA) and season of birth in a sample of first-episode patients with schizophrenia, schizophreniform disorder, and affective disorder with psychotic features, and in a normal control group. Patients with schizophrenia who were born during the season of excess risk (January-April) were less responsive than those born during other times of the year. They had lower skin-conductance levels and fewer skin conductance responses. No such effects were found in patients with schizophreniform or affective disorder, or in the normal subjects. When compared with the control group, winter-born schizophrenics showed significantly more evidence of hyporesponsivity. In contrast, nonwinter-born patients did not differ from normal subjects in skin-conductance level or number of skin-conductance responses. Schizophreniform patients born during the other seasons of the year were more likely to be hyporesponsive. The above results provide supporting evidence for the validity of the season of birth phenomenon. We hypothesize that a viral infection, or some other perinatal complication associated with winter and early spring births, leads to temporal lobe damage and consequent dysregulation of electrodermal activity in patients with schizophrenia. PMID- 1643199 TI - Thyroid hormones, body temperature, and antidepressant treatment. PMID- 1643200 TI - Effects of platelets and plasma on fibrinolysis. AB - The effects of various concentrations of platelets and plasma on in vitro t-PA induced fibrinolysis were investigated. At t-PA levels between 30 and 70 ng/ml, fibrinolysis proceeded faster in platelet-rich plasma (PRP) than in platelet-poor plasma (PPP). When PRP was serially diluted with PPP and the rate of fibrinolysis compared to PPP, higher platelet counts (up to 300 x 10(9)/l) were associated with increased enhancement of lysis. However, lysis was inhibited when platelets were added to plasma diluted with buffer. Thus, platelets enhance fibrinolysis in undiluted plasma but inhibit lysis in diluted plasma. This is probably because platelets provide a catalytic surface for fibrinolysis but also release inhibitors of fibrinolysis. In undiluted plasma, there would be sufficient fibrinogen and plasminogen to overcome the effect of the platelet inhibitors, but in diluted systems, the inhibitors would predominate, retarding fibrinolysis. PMID- 1643201 TI - Physiological inhibitors of coagulation in fulminant hepatic failure. AB - To study the effect of the severe loss of hepatic synthetic function on the inhibitors of coagulation we have measured protein S (total and free), protein C, heparin cofactor II and antithrombin III in 30 patients with fulminant hepatic failure. The results showed severe reduction in all inhibitor levels with mean (+/- SE) values of: protein S, 0.26 +/- 0.03 U/ml; protein C, 0.26 +/- 0.03 U/ml; heparin cofactor II, 0.12 +/- 0.02 U/ml and antithrombin III, 0.21 +/- 0.02 U/ml. Heparin cofactor II was significantly lower than the other inhibitors (P less than 0.01). Although the reduction in free protein S was significant in fulminant hepatic failure as compared to normal subjects (0.40 +/- 0.05 U/ml compared to 1.02 +/- 0.08 U/ml, P less than 0.001), the ratio of free to total protein S was significantly increased (0.67 +/- 0.02 compared to 0.40 +/- 0.04, P less than 0.01). Prothrombin time (INR) was significantly inversely correlated with total protein S (r = -0.56, P less than 0.001) and free protein S (r = -0.48, P less than 0.01), but not with the ratio of free to total protein S. No significant correlation between the different coagulation inhibitors and other measures of hepatic function could be detected. Although the loss of hepatic synthetic function appears to be the major cause of the loss of coagulation inhibitors, other effects such as increased consumption and rate of clearance may play a role. The balance of these will be reflected in the circulating levels of the coagulation inhibitors. PMID- 1643202 TI - Protein S negates the activated protein C inhibitory activity of plasma. AB - The inactivation of factor Va by the natural anticoagulant, activated protein C (APC) is subject to a number of regulatory mechanisms. This report examines the efficacy of APC in plasma and evaluates the role of the APC cofactor protein S in this milieu. The ability of protein S to enhance the anticoagulant effects of activated protein C was demonstrated using a factor Xa recalcification time of Al(OH)3 adsorbed plasma. At a set concentration of APC, increasing concentrations of protein S resulted in a linear and saturable potentiation of the activity of APC. This result was not reflected in a purified component assay, where the extent of factor Va inactivation by APC was only marginally augmented by protein S. The efficacy of the cofactor was not affected by variations in the concentration of factor Va. Similarly, increasing the protein S:APC molar ratio of 200:1 resulted in only a trivial enhancement of APC activity. To directly examine the proteolysis of factor Va by APC in plasma, a novel assay system containing Al(OH)3 adsorbed, factor V deficient plasma supplemented with purified human factor Va was developed. The addition of APC in varying concentrations to this system consistently yielded factor Va inactivation rates inferior to those seen in a purified component assay. This finding is consistent with the presence of APC inhibitory activity in plasma. When protein S was added to the plasma system, factor Va inactivation by APC was restored to a similar level to that observed in the purified system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1643203 TI - An ELISA for tissue factor using monoclonal antibodies. AB - Whereas tissue factor, a high-affinity cell-surface receptor and essential cofactor for the serine protease factor VII is constitutively present in certain tissues such as epithelial tissue, brain and placenta, it is not normally expressed by cells within the vasculature. However, the stimulation of monocytes and endothelial cells by a variety of inflammatory and immunological reactions results in the induction of cell surface tissue factor (TF) expression. TF is also expressed on tumour cells, and may play a role in tumour growth and metastasis formation. To examine the role of TF in these processes we developed monoclonal antibodies to human tissue factor apoprotein. The antibodies were characterized by neutralization of the procoagulant activity and by immunoblotting. With two of these monoclonal antibodies a sandwich ELISA was developed for the rapid quantitation of TF. The sensitivity of the assay permits extensive studies involving the modulation of TF expression on small numbers of cells. The results are comparable to the functional clotting assay as evaluated with unpurified TF and with the tumour cell line MCF-7. For certain applications, monitoring of cellular TF expression by ELISA using anti-TF monoclonal antibodies is preferable because it is not influenced by other coagulation factors or by inhibitors of procoagulant activity on the cells. PMID- 1643204 TI - Increased hydrogen peroxide formation in platelets of patients affected with essential thrombocythaemia (ET). AB - The basal platelet level of reactive oxygen species and their enhancement following stimulation by different agonists were determined in a selected group of patients with essential thrombocythaemia (ET). Activated platelets had lower levels of superoxide anion and higher intracellular concentrations of hydrogen peroxide than controls. Higher levels of lipid peroxidation induced by N ethylmaleimide were also observed. Measurement of the most important enzymes generating and scavenging these reactive oxygen species revealed increased specific activities of NADPH-cytochrome c reductase and superoxide dismutase and a decrease in platelet catalase activity in patients with ET. Since an abnormal production of oxygen radicals seems to be implicated in various pathological conditions and aging processes, the increased amount of hydrogen peroxide found in platelets of patients could be involved in some of the platelet alterations described in ET. PMID- 1643205 TI - Fibrin clots obtained from plasma containing heparin show a higher sensitivity to t-PA-induced lysis. AB - Although heparin is currently used in concomitance with thrombolytic agents to improve their efficacy, its effect on fibrinolysis is controversial. We have evaluated the sensitivity to t-PA-induced lysis of clots prepared from plasma preincubated in vitro with therapeutic concentrations of heparin. The extent of t PA-induced lysis was significantly increased by preincubation of plasma with 0.5 and 1.0 U/ml heparin. The concentration of t-PA required to give similar lysis rates were reduced by up to five times after adding 1.0 U/ml heparin to plasma prior to clot formation. Heparin added to the t-PA-containing medium after clot formation did not exert any significant effect. The effect of heparin was not mediated by the inhibition of thrombin as preincubation of plasma with hirudin did not modify clot sensitivity to t-PA. We also found that heparin significantly modified fibrin assembly and clot structure as assessed by a turbidimetric assay. Pre-incubation of fibrinogen with heparin caused an increase in the speed of fibrin fibre polymerization and in the turbidity of the final fibrin gel; changes known to be associated with the formation of thicker fibrin fibres. Thus the effect of heparin on clot sensitivity to lysis appears to be due to an increased permeability of these clots to fibrinolytic components. This may contribute to the antithrombotic activity and to the haemorrhagic risk of heparin. These findings could be particularly important for clinical thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1643206 TI - The preparation of a sensitive partial thromboplastin reagent from bovine brain. AB - Commercial partial thromboplastin reagents markedly differ in their sensitivity to factor deficiency, heparin, or the lupus anticoagulant. These differences may be partly due to the variable phospholipid content of different commercially available reagents. For over 15 years, we have routinely used a partial thromboplastin prepared from human brain. In the past four years, we have been using a similarly prepared bovine partial thromboplastin reagent. This report describes the preparation of our partial thromboplastin reagent, as well as an analysis of the phospholipid composition of both the human and bovine thromboplastin reagents. Four separate brain preparations produced consistent percentages of the anionic phospholipids, phosphatidylserine, and phosphatidylinositol. The bovine reagent was also compared with commercial partial thromboplastin reagents in the detection of coagulation factor deficiency, heparin, and the lupus anticoagulant. PMID- 1643207 TI - Study of the protein S system in HIV-infected patients: acquired protein S deficiency or unsuitable assays? AB - The plasma protein S (PS) system was studied in 120 HIV seropositive patients (CDC classification: group II: n = 35; group III: n = 6; groups IVA, IVC2 or IVE, n = 38; groups IVB, IVC1 or IVD, n = 41). Total PS antigen and C4b-binding protein (C4b-BP) values were not significantly different from control values. Free protein S levels assessed by an immunological method in the supernatant of PEG-precipitated plasma samples (PEG-fPS) were below the normal limit in 85 patients, lower values being found in patients with advanced HIV disease. No correlation was found between PEG-fPS levels and C4b-BP or total PS levels. At least 25 patients had a low functional PS value. Low functional levels of PS were found in each clinical group although there was no difference in the distribution of functional PS values among groups. Crossed immuno-electrophoresis showed an abnormal distribution of PS in some patients, but failed to confirm the marked decrease of free PS in patients with very low PEG-fPS. An impairment of the protein S system is observed in HIV-infected patients. However, the discrepancies found in some patients among the results of the various PS-related assays should lead to a cautious interpretation concerning the incidence of PS deficiency in HIV-infected patients. PMID- 1643208 TI - A one-step enzyme immunoassay for the determination of total tissue-type plasminogen activator (t-PA) antigen in plasma. AB - A reproducible and sensitive one-step enzyme immunoassay (EIA) was developed to determine total tissue-type plasminogen activator (t-PA) antigen in plasma. The EIA comprises two monoclonal catching antibodies and a polyclonal (goat) tagging antibody conjugated with horseradish peroxidase. There is an equal reactivity towards the several physiological t-PA forms, i.e., single-chain t-PA, two-chain t-PA and t-PA in complex with its naturally occurring inhibitor plasminogen activator inhibitor-type 1 (t-PA/PAI-1 complex). Additionally, the EIA does not discriminate between human melanoma t-PA and recombinant t-PA (Activase). The assay has a lower detection limit of approximately 0.5 ng t-PA per ml plasma, with a time-to-result of only 3.5 h. PMID- 1643209 TI - Increased lipopolysaccharide-induced tissue factor activity and tumour necrosis factor production in monocytes after intake of aspirin: possible role of prostaglandin E2. AB - To determine how aspirin intake might influence lipopolysaccharide (LPS)-induced tissue factor (TF) activity and tumour necrosis factor (TNF) in human blood monocytes, we collected blood before and at various times after intake of 300 mg aspirin in 25 healthy volunteers. Aspirin intake reduced LPS-induced thromboxane B2 and PGE2 production in whole blood by 50% and 65% respectively, measured 1 h after aspirin intake. Subsequently, a 95% rise in LPS-induced TF activity in monocytes was seen as compared to a 26% rise in TNF. The rise in TF activity was maximal within 1 h after aspirin intake and no further rise was observed 3, 4 or 24 h after aspirin intake. In contrast, TF activity induced by incubating whole blood in the absence of LPS fell rapidly after the intake of aspirin. In separate experiments, a dose-dependent inhibition by PGE2 was observed in LPS-induced TF activity in monocytes. It is proposed that the increased LPS-induced TF activity and TNF production following aspirin intake may be due to suppressed PGE2 formation. The more pronounced rise in TF activity compared to TNF production may be due to an enhancement of the platelet lipoxygenase pathway that has been shown to be important for LPS-induced TF activity in monocytes. PMID- 1643210 TI - Antithrombin and its deficiency states. AB - Antithrombin is the most important physiological proteinase inhibitor of thrombin and other coagulation proteinases. It is a single chain glycoprotein of MW 58,200 which has sequence homology with alpha 1-antitrypsin and other members of the serpin superfamily of inhibitors. Two functional domains of importance have been identified, the reactive centre that interacts with the proteinase and a heparin binding domain. Failure to maintain an adequate level of functional antithrombin in plasma results in an increased risk of thromboembolism: deficiency can be inherited or acquired. There is still uncertainty regarding the prevalence of inherited deficiency and the prevalence of thrombosis in affected individuals. The production of antithrombin is under the control of a single gene which is localized on chromosome 1q 23-25. Characterization of the coding sequence, which is distributed over seven exons, has allowed the analysis of the molecular basis for inherited antithrombin deficiency. To date more than 100 cases have been successfully investigated at the gene and/or protein sequence level and 40 novel mutations have been identified. Mutations causing amino acid substitutions solely affecting the heparin binding site have thus far been located primarily at the N terminal region of the molecule, residues 7-129; this region has been postulated to align as a positive groove in the molecule that forms the primary contact region for the essential antithrombin binding pentasaccharide of heparin. Not all the residues in which substitutions have been found are basic and some serve to maintain the conformation of nearby basic regions. Examples of this are provided by the Pro-41 to Leu mutation and a recently investigated mutant, Leu-99 to Phe. The reactive site defects are an interesting group, including those that alter P1, P1' and P12-P10 residues. Perhaps more remote mutations can also be included such as Pro-429 to Leu. The P1 and P1' mutations directly block interaction of the proteinase with anti-thrombin, while P12-P10 mutants (which have mutations affecting serpin strand s4A) enable the substrate reaction to proceed to completion, i.e. the antithrombin-thrombin complex is not stabilized and the mutant inhibitor is transformed into a substrate. The effect of the Pro-429 to Leu substitution is impairment of the reactive site and heparin binding, and the finding that this variant is not completely recognized by some MAbs implies a conformational change at the C terminus. Another group (nine cases) of interesting mutations is emerging, that has its primary defect in or near serpin strand 1C, amino acid sequence 402-407.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1643211 TI - A programmable stimulator for electrophysiological studies. AB - We report on the design and construction of a programmable stimulator for use by neuroscientists. The stimulator is small, lightweight, and low powered. It generates positive, negative, or positive and negative pulses with widths and periods programmed by the user. The stimulator has ten parallel outputs to enable it to drive ten preparations at one time. It operates from 50-60 Hz, 115 v AC or 230 v AC and had a nominal peak-to-peak output of 30 volts. A liquid crystal display was used for the user interface and the timing was software-generated by a mincrocontroller. PMID- 1643212 TI - Physiological monitoring techniques for home health care. AB - Practical techniques of nonconstrained physiological monitoring which are acceptable in daily life have been attempted, and obtained preliminary results: Successive records of temperature profile on a bed provide information such as body movement, and sleep hours. ECG can be recorded automatically in a bathtub with electrodes on the inside wall of the tub. Heart rate can be measured by ECG taken at a toilet seat. Proposed techniques do not require any effort of measurement procedure to the subject, and thus it is expected that physiological data can be accumulated automatically even though subjects never aware the monitoring procedure. PMID- 1643213 TI - Automated situational analysis for operating room anesthesia monitoring. AB - The hospital operating room (OR) is an environment that requires up-to-the minute, reliable information on a patient's state. Data is usually provided by a heterogeneous mixture of independent monitors that, due to their isolated nature, give complex and sometimes erroneous presentations of a patient's state. This complex presentation introduces the possibility of operating room personnel overlooking data items that indicate certain pending patient states, such as cardiac arrest. A computer based system that collects the various monitor data, summarizes its content, and provides concise discourse on a patient's state (including potential life threatening situations), would be beneficial. PMID- 1643214 TI - Development of a microcomputer-based system to quantify the effective dose of drug through epithelial cells. AB - It is well documented that the rate-limiting step of pharmaceutical investigation is the amount of drug absorbed through the epithelial cells, not the total dose taken. To date, the only measure of the effective dose of medication is by measuring the circulating level of the ingested medication. This mode of measurement is neither accurate nor practical in determining the active ingredient required. However, a more efficient method of testing which constitutes simplicity and practically is desired. The aim of this project was the design of a microcomputer-based system for detecting and quantifying steroid hormones taken up by mucosal intestinal cells in vitro, for eventual in vivo application in animals and humans. A microcomputer-based system capable of controlling and monitoring four cell membranes simultaneously has been designed, consisting of a microcomputer system and a data acquisition subsystem. The data acquisition subsystem consists of instrumentation amplifiers with an analog-to digital converter and digital-to-analog converter. This subsystem converts the ionic exchanges first to electrical signals, and then to digital format, to be processed and stored by the microcomputer. Subsequently, the stored information can be clinically interpreted. Due to the complexity of membrane behavior (nonlinear) in response to feedback control signals, software development was difficult. Therefore, a unique scheme was developed to control various unexcitable tissues in order to reach the predetermined values very rapidly, and then to collect cell membrane data periodically. PMID- 1643215 TI - Biocompatibility of ferric calcium phosphorous oxide ceramics. AB - The objective of this investigation was to ascertain the biocompatability of a ferric calcium phosphorous oxide ceramic (FECAP). The FECAP ceramic was fabricated from stock powders combined in a ratio of 46:40:14 by weight of Fe2O3:CaO:P2O5. The composite oxides were mixed for homogeneity, pressed into a 20g block, and calcined in a crucible at 1100 degrees C for 12 hours. The calcined ceramic was then ground in a ball mill before separation into particle sizes of 38-45 microns and 63-75 microns, by an automatic siever and shaker. Calcined powders of each particle size were mixed with polyvinyl alcohol binder (0.025g PVA/1.0g of FECAP), and pressed into 0.5g pellets in a 5/16" (internal diameter) die at a 1820 kilogram load using a Carver hydraulic press. FECAP pellets were then sintered at 1100 degrees C for 12 hours. For this investigation, sixty albino (Sprague-Dawley) rats weighing 125-425 g each, were distributed into four groups: non-operated controls, sham-operated controls, and two groups subcutaneously implanted with ceramics 38-45 microns and 63-75 microns FECAP ceramics, respectively. Three rats from each group were sacrificed at three, five, seven, and twenty-one days post-surgery. Morphologic examination of the implant and implant site as well as hematocrit data indicate that this ferric calcium-phosphorous oxide ceramic is biocompatible. Data obtained todate suggest that sintered FECAP should have a wide variety of dental and medical applications, especially where iron deficiency is a concern. PMID- 1643216 TI - Characterization of ceramic drug delivery devices: the effect of various temperature of incubation on the delivery of biologicals. AB - The objectives of this study are: (i) to determine the effect of temperature on the release rate of steroids and proteins from ceramic drug delivery devices (CDDD), and (ii) to examine the effect of polylactic acid (PLA) impregnation of tricalcium phosphate (TCP), and alumino-calcium-phosphorous oxide (ALCAP) ceramic capsules on the release of small and large molecular weight compounds, and (iii) to investigate the interaction of molecular weight and various incubation temperatures (25, 37 and 50 degrees C) on the rate of delivery from CDDD. The CDDD were prepared using standard laboratory protocols. Eight of 16 ALCAP and TCP ceramic capsules were impregnated with PLA and the remainder fabricated without PLA. Fourteen ceramic capsules were loaded with either 40 mg of testosterone or 40 mg of bovine serum albumin (BSA), and nothing was added to the two remaining capsules. All capsules were then sealed at both ends with Dow Corning Type A Silastic Medical Adhesive. Single capsules were suspended in serum bottles containing either 100 ml of 50% wt/vol aqueous ethanol solution (steroid containing capsules) or 100 ml of phosphate buffered saline (pH 7.4) (protein containing capsules). The bottles were then placed in one of three metabolic shaker baths that had been previously adjusted at 25, 37, or 50 degrees C and were oscillating at a frequency of 100 rpm. Testosterone release was measured spectrophotometrically at 245 nm and BSA by a colorimetric procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1643217 TI - Numerical study of arterial flow during sustained external acceleration. AB - A computer model of the human arterial tree based upon the one-dimensional flow equations is used to study the effects of sustained acceleration (+Gz) on eye level arterial pressure and flow. Steady-state physiological compensatory mechanisms are modelled using human centrifuge data found in the literature. Cases investigated include the supine and standing human (+1 Gz), the application of resistive and occlusive anti-G suits, and the occurrence of a stenosis proximal to the carotid bifurcation. Results indicate that the simulated eye level pressures and flows satisfactorily correspond with those found in the literature. PMID- 1643218 TI - Virtual instrumentation for frequency analysis of carotid sinus responses. AB - An advanced microcomputer based process control and instrumentation system was developed for real time frequency analysis of the viscoelastic relationships between the carotid sinus wall and indwelling baroreceptors. A 486 based AT bus microprocessor running data acquisition and visualization software was customized providing a virtual instrument for data collection, display, and recording. A full complement of signal processing algorithms was developed for the collection of large time sampled data sets and their conversion to the frequency domain for analysis. Polynomial curve fitting procedures were used for transfer function estimation of wall viscoelastic properties. Simulated in situ sinus data was collected and analysis was used to test the methodology. PMID- 1643219 TI - Design: a voice activated thermostat. AB - The voice activated thermostat was designed so the temperature in a house could be set without having to touch the thermostat. This is especially useful for a quadriplegic who would like to change the temperature of the room he is in. For simplicity, it was designed using VCP200 speaker-independent word recognizer chip. This chip comes pre-programmed with a limited number of words, so programming of words was not necessary. Every time the activation word is said the digital thermostat changes by one degree. PMID- 1643220 TI - Mathematical modelling of post-exercise heart rate recovery in ponies. AB - Using a recently developed nonlinear algorithm which identifies reference points on left ventricular pressure waveforms and other waveforms, we analyzed heart rate recovery in ponies after strenuous treadmill exercise. Each pony performed exercise tests with and without premedication with atropine methyl nitrate. Resting and exercise heart rates were 54 +/- 3 and 209 +/- 6 beats/min, respectively, without premedication and 85 +/- 8 and 212 +/- 5 beats/min, respectively, following atropine premedication. Post-exercise heart rate recovery without premedication was best described by a biexponential curve with a rapid initial period (duration = 55 +/- 6 sec, Tl/e = 15 +/- 2 sec) and a slower secondary period (duration = 267 +/- 5 sec, Tl/e = 455 +/- 78 sec). After atropine premedication, heart rate recovery followed a monoexponential curve (Tl/e = 174 +/- 46 sec) in 4 ponies, but remained biexponential (Part 1 duration = 74 sec, Tl/e = 20 sec; Part 2 duration = 243 sec, Tl/e = 342 sec) in the other ponies. The calculated time required for heart rate to return to resting levels after atropine premedication was 11.3 +/- 2.2 min, compared to 26.3 +/- 3.9 min without premedication. However, without premedication, only 6.6 +/- 1.6 min were required to reach the post-atropine resting heart rate, indicating that the time difference was due to the higher resting heart rate after atropine premedication. Thus, heart rate recovery in the non-premedicated pony follows a biexponential curve similar to that observed in other species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1643221 TI - Determining the efficacy of edge detection algorithms. AB - Edge detection is an important process in the interpretation of image data. Four types of edge detection algorithms (the Local Variance, Correlation, Laplacian and Frequency Peak algorithms) are compared for their ability to discriminate the edges present in an image with precisely defined edges. The variety of techniques are discussed in terms of their sensitivity to the presence of edges and their sensitivity to the applied noise. Both computational and empirical analyses are presented, and the relative merits of each discussed in terms of signal-to-noise ratio, sensitivity and computational difficulty. It is shown that local variance edge detection is an acceptable method for edge detection which simplifies the computation needed for image convolution. The means through which to devise more sophisticated edge detection algorithms is outlined, and the use of difference images to discriminate edges in an image is discussed. The results are also discussed in terms of the implementation of edge detection algorithms as part of a computer visual system which has an architecture modeled after the mammalian visual system. PMID- 1643222 TI - Endothelial vasoactive influence simulated by exponential feedback. AB - We hypothesized that results from rabbit carotid sinus wall and baroreceptors could be simulated using exponential feedback in a viscoelastic model. Wall and baroreceptor were each modeled by second order differential equations. Coefficients for viscosity, elasticity and feedback were estimated from experimental data. Feedback of model wall distension (y1) on viscosity (C) was expressed by the transfer function: C/y1 = RW/(s tau W + 1). With gain (RW) = 52.5E6 N(s)/m2 and tau W = 34 sec, this feedback resulted in simulation of wall response for sinuses with intact endothelium. Model receptor required no (or negative gain) feedback to simulate baroreceptors. PMID- 1643223 TI - Insulin delivery by zinc calcium phosphate ceramics. AB - Zinc-calcium-phosphorous oxide (ZCAP) ceramics were developed to deliver insulin in vivo in rats. Thirty-nine Sprague-Dawley male albino rats (Holtzman Co., Madison, WI), weighing 260 +/- 15 g each, were randomly distributed into six groups: normal controls (3), sham controls (3), diabetic controls (6) and three diabetic experimental groups each consisting of nine rats. Diabetes was induced in rats by an intravenous injection of Streptozotocin (75 mg/kg body weight). Rats in the three diabetic experimental groups were implanted subcutaneously with two ZCAP capsules, each containing 10, 15, or 20 mg of insulin. Blood glucose measurements were taken at least twice a week over a six week period. Plasma insulin levels were measured at two, four, and six weeks by a radioimmunoassay using 125I labeled insulin. Normoglycemia was maintained for three weeks in rats implanted with ZCAP capsules containing a total of 20 mg of insulin. Plasma insulin levels correlated with the normal blood glucose levels in these rats. Thus, ZCAP capsules could be used to deliver insulin and maintain normoglycemia in diabetic rats. PMID- 1643224 TI - Zinc sulfate calcium phosphate (ZSCAP) composite for repairing traumatized bone. AB - The objective of this investigation was to evaluate the suitability of zinc sulfate calcium phosphate ceramic composites as bone substitutes. ZSCAP ceramics were fabricated from stock powders of zinc sulfate, zinc oxide, calcium oxide, and phosphorous pentoxide in a ratio of 15:30:30:25 by weight of ZnSo4:ZnO:CaO:P2O5. The three oxides and zinc sulfate were mixed for 10 minutes in a blender and then calcined in a crucible at 650 degrees C for 24 hours. The calcined powder was ground in a ball mill for 0.5 hours and separated into particle sizes of 38-45, 45-63, and 65-75 microns by an automatic siever and shaker. One hundred male, albino, Sprague-Dawley rats, weighing 250-300 g each, were used to conduct the investigation. The treatments (10 rats per treatment) were as follows: Group I, non-operated controls, Group II, sham-operated controls, and Groups III, IV and V, experimental animals. In situ hardening ZSCAP ceramic particulate powders or pastes of 38-45 microns (Group III), 45-63 microns (Group IV) or 65-75 microns (Group V) were implanted in a 2.0 mm defect in the femur of each rat. Radiographic and morphologic examination of the implant site indicated that the implant was biocompatible and firmly entrenched in the traumatized bone defect up to 90 days post-implantation. Since ZSCAP ceramics set like plaster of Paris and have all the beneficial properties of resorbable calcium phosphate, they should provide the surgeon with a non-toxic, resorbable, fast setting ceramic (in situ) for use as a hard tissue substitute in orthopaedic, dental, and maxillofacial surgeries. PMID- 1643225 TI - Electronic ECG simulator. AB - This paper describes the design of an ECG simulator which outputs both normal and abnormal waveforms. Both heart rate and signal amplitude may be controlled. Applications include a test signal source for repair/maintenance of ECG monitoring equipment, and as a laboratory simulation device for student educational use. PMID- 1643226 TI - Stimulus presentation using a programmable signal generator. AB - Event related potential experiments frequently require the presentation of complicated stimulus patterns to the subject. As the complexity and number of different types of stimuli presented to the subject increase there is a corresponding increase in the amount and complexity of the equipment required to generate the stimuli. Software was developed for complex stimulus presentation which uses a programmable arbitrary/function generator. The various stimulus patterns are stored in digital form in the memory of the signal generator and can be recalled by number. Prior to presentation of a particular stimulus pattern the number of that pattern is sent by the control program to the generator for recall from memory. The signal generator is set to operate in external trigger mode and at the proper time for stimulus presentation the generator is triggered by the control program. The use of the programmable signal generator allows replacement of the typical stimulus presentation equipment such as gates, signal generators, and attenuators by this the programmable generator and provides getter flexibility as to the type and complexity of stimuli which can be generated. PMID- 1643227 TI - Selecting a stimulus signal for linear systems analysis of the vestibulo-ocular reflex. AB - We evaluated 3 types of stimulus signals for use in estimating the transfer function of the vestibulo-ocular reflex. We used individual sine-wave, sum-of sine, and pseudorandom stimuli. Five normal human subjects were tested 5 times each using each of the 3 stimulus types. Frequency domain techniques were used to estimate the transfer function at 0.01, 0.03, and 0.05 Hz. The most consistent estimates were obtained using individual sine-wave stimuli. The pseudorandom signal yielded the most variable estimates. A sum-of-sine stimulus composed of 3 sine-wave signals provided estimates slightly more variable than the individual sine-wave stimuli, but much less variable than the pseudorandom stimulus. The redundency of the sine and sum-of-sine stimuli seems to be an advantage by providing stable estimates of the transfer function in the presence of noise. PMID- 1643228 TI - Template matching techniques for electrophysiologic signals: a practical, real time system for detection of ventricular tachycardia. AB - Time domain template matching morphology techniques have been proposed for inclusion in implantable cardioverter defibrillators (ICDs) for the detection of ventricular arrhythmias from intraventricular electrograms (IVEGs). However, ICDs have limited battery capacity which necessitate the use of low current drain algorithms. Although more computationally efficient template matching algorithms have been developed, none have incorporated the limitations inherent in current ICDs. An external ICD sensing prototype system was developed which filters, digitizes, and analyzes IVEGs during electrophysiology studies. Two template matching IVEG metrics, amplitude normalized area of difference and signature analysis, are calculated. These metrics are being tested clinically for their accuracy in differentiating ventricular tachycardia and sinus rhythm IVEGs. PMID- 1643229 TI - Comparison of the frequency spectra of surface electromyographic signals from the soleus muscle under normal and altered sensory environments. AB - The vestibular, proprioceptive and visual senses of the body are all affected by alterations of the normal sensory environment during weightlessness. This study was designed to observe muscle activation characteristics when a single component of the sensory environment was altered. Partially immersing a subject in a water pool provided a buoyant force upon the lower body, "unloading" the muscles, similar to the effect on the muscles in weightlessness. Surface EMG from the soleus was obtained during the performance of a constant-force isometric contraction. The mean and median characteristic frequencies were calculated from the power spectrum of each trial. Six of ten subjects showed a difference in the characteristic frequencies between the two environments. It appears that for some individuals there are changes in muscle activation characteristics due to influences of the proprioceptive system when exposed to an altered sensory environment. PMID- 1643230 TI - EEG dynamics. Brain processing of sensory and cognitive information. AB - The EEG oscillations and resonances before sensory stimulation are variable; unstable frequencies and amplitudes. The EEG time-coherency is variable and tends to be incoherent preceding sensory stimulation. The phase angle of the EEG between brain structures tends to be random and coherence between various brain structures is low before the stimulus. Following sensory stimulation, the frequency is stabilized and the amplitude is greatly enhanced. These responses are considered to be related to coupling of neural oscillators and nuclear resonance. The shift to a time-coherent state is considered to be related to a probabilistic harmonic oscillators. The phase angle after the stimulus is zero phase in the brain rhythm channels in all brain structures as noted in the phase spectra. In the post stimulation period there is a change to high coherency between brain structures in the inherent frequencies of their brain rhythms. Internal evoked potentials shown in all the brain nuclei studied. All the frequencies in the evoked potential responses are dependent on spontaneous EEG activities prior to the stimulus. PMID- 1643232 TI - Intersegmental elbow joint load during pushup. AB - Intersegmental loading pattern on the elbow joint during a push-up exercise was investigated. Electromagnetic motion sensors and a piezoelectric force plate were used to simultaneously record upper extremity motion and forces on nine healthy male subjects during push-ups in six different hand positions. Peak axial forces exerted on the elbow joint averaged 45 percent of the body weight. Peak torque to produce elbow flexion was 2305.9 N-cm, or 56 percent of maximal isometric extensor torque. The results of this analysis give insight to the biomechanics of a normal elbow and to its load carrying capacity. PMID- 1643231 TI - Brain states--brain rhythms--brain responses. AB - Oscillation and resonance of electrical activity of certain sets of neurons in the brain and spinal cord is an important factor in the organization of those properties of connectivity that must be tuned by function. Once connectivity has reached some degree of specificity important biological and chemical events must occur to stabilize synaptic inputs and localize excitable sites to particular areas of the cell surface. It has been proposed that intrinsic electroresponsiveness generates internal computational states that serves as a reference frame or context for incoming information. The intrinsic activity is proposed to be a part of the vectorial coordinate space that sensory and motor transformations occur in context of a particular functional state such as attention and expectation that can modify the relevance of a given sensory input. The most significant mechanism in generation of oscillation properties of the brain are the intrinsic properties of individual neurons. This concept presents a shift of emphasis from properties of circuits to properties of single neurons. Feedback circuits and synchronization of single oscillators into sets of coupled oscillators which in turn generates field potentials such as (EEG) and evoked response (ER). PMID- 1643233 TI - An integrated approach to rehabilitation engineering education: the development of a new masters programme at Brunel University. AB - We report on a new multidisciplinary course at Master's Level; a joint venture between the Department of Design at Brunel University. U.K. and Brunel Institute for Bioengineering. The Bachelor of Science degree in Industrial Design at Brunel includes an important proportion of technological courses such as mechanics and electronics. The MSc course, which is modular, continues to embrace a wide range of disciplines but it also seeks to bring together graduates from traditional engineering backgrounds in addition to those from arts based design courses. Appropriate elements are offered in order to allow access into unfamiliar disciplines. One novel and valuable aspect of the course is the way in which graduates from diverse backgrounds, having complementary experience and skills will be studying and developing projects alongside one another. Although much of the academic content will be through the department of Design and the Faculty of Technology, the Brunel Institute for Bioengineering will play a major role in the provision of modules in Rehabilitation Studies and in the generation and supervision of projects. This project work will therefore be carried out within the Rehabilitation Engineering Unit at Brunel Institute for Bioengineering. The course to be discussed has been developed at Brunel University in the department of Design in conjunction with The Brunel institute for Bioengineering. PMID- 1643234 TI - Learning to count. AB - The "Learning to Count" is a microprocessor controlled device constructed to help teach a developmentally disabled individual to learn to count to ten. The device has ten buttons, each with two numerical seven-segment LED's displaying a random number 1 through 10. The game's objective is for the student to press the ten buttons in numerical order. A microprocessor and integrated circuits carry out the device's internal operations. The microprocessor controls the generation of the random numbers, the assigning of the random numbers to a button position, and the analysis of the button input. The integrated circuits transfer the information from the microprocessor to the displays and from the input buttons to the microprocessor. PMID- 1643235 TI - The next generation of students, are you ready? AB - School administrators across the country are under pressure from parents, community leaders and politicians to improve the public education system for the average student. As a result, several new programs are being studied, developed and implemented in grades K through 12. These programs will impact several areas at the public school building level from K through 12: 1) Goals for multicultural learning; 2) The grade structure and objectives at the elementary, middle and high school levels; 3) The use of technology in all subjects; 4) Open and direct teaching of critical thinking skills in all courses; 5) Methods of assessment which include self assessment and portfolios as well as standardized tests; and 6) The incorporation of the guaranteed high school diploma. PMID- 1643236 TI - Contractile wire biomechanical actuators. AB - Several metal alloys have been discovered which, when fabricated into wire, contract strongly when heated and relax with cooling. The contractile force can be modulated under microcomputer control to produce a compact, powerful and durable mechanical actuator. This technique has a number of advantages over motor driven servos in robotics and medicine. This paper reviews previous applications of contractile wire, then presents two types of biomechanical actuators built by the author. PMID- 1643237 TI - An evaluation of two commercially available noninvasive blood pressure monitors in the canine. AB - The objective of this experiment was to evaluate whether two commericially available noninvasive blood pressure monitors could be adapted for animal use, specifically, in the dog. Five dogs were anaesthetized and had femoral canulas surgically implanted into the left rear leg to record invasive blood pressure. A blood pressure cuff was placed on the right leg and connected to a commonly used noninvasive blood pressure monitor. Hyper- and hypotensive states were induced pharmaceutically. Invasive and noninvasive measurements were compared under normal, hyper- and hypotensive states. PMID- 1643238 TI - Differential features for a neural network based anesthesia alarm system. AB - We have developed a neural network based alarm system that identifies 19 specific faults in the anesthesia breathing circuit, such as "Inspiratory Hose Leak," or "Y-Piece Disconnection." CO2, pressure, and expired flow waveforms, along with ventilator settings, were sampled by a personal computer. Fifty-two features, such as "maximum CO2" or "minimum pressure", were extracted from each breath, converted to "differential" features, normalized, and used as the inputs of a three layered feed-forward neural network. The network was trained, using backward error propagation with momentum, to classify each breath as normal or containing one of 19 faults. To collect the neutral network training set, seven dogs were anesthetized and ventilated using controlled ventilation. Each of 19 faults were created over a range of ventilator settings and fresh gas flows. The neural network correctly identified 83.1% of 550 events presented to it during testing. These preliminary results are an encouraging example of neural network applications in the field of clinical monitoring. PMID- 1643239 TI - Molecular motions and thermotropic phase behavior of triacylglycerols and cholesteryl esters in herpesvirus-infected arterial smooth muscle cells: a deuterium nuclear magnetic resonance study. AB - The physical state of lipids in arterial smooth muscle cells (SMC) may contribute to lipid accumulation following injury. We have previously demonstrated that herpes simplex virus (HSV) infection alters the physical state of the neutral lipid accumulating in arterial SMC, as determined by differential scanning calorimetry (Biochem. J. 268 (1990) 693-697). To more precisely determine the molecular packing of neutral lipids in HSV-infected cells, the influence of HSV infection on the thermotropic and phase-behavior of the lipids in intact arterial smooth muscle cells and in cell-free lipid extracts was evaluated using [2H]-NMR, employing U-[2H]-oleic acid incorporated into cells. Inspection of the [2H]-line widths indicate that the lipid of HSV-infected cells exhibited more restricted motion or a greater chemical shift dispersity than lipids from uninfected cells, as evidenced by significant broadening of the -CD = CD- signals at 25 degrees C and 45 degrees C. Fatty acid compositional analysis of the neutral lipids of control and HSV-infected cells following C18:1 supplementation (an amount added similar to the NMR experiments) reveals that: (1) there is approximately 55-fold more triacylglycerols (TG) than cholesteryl esters (CE) in control cells and 40 fold more TG than CE in the HSV-infected cells; (2) HSV infection significantly increases the C18:1 content of CE, and C18:3 and C20:4 in TG; and (3) HSV infection does not alter the ratio of TG to CE. These data support the hypothesis that the greater restriction of the neutral lipids in HSV-infected cells may be due to the rigidifying effects of C18:1 on lipid mobility. Thus, alterations in the physical state of neutral lipids in HSV-infected cells may lead to reduced CE hydrolysis which, in turn, may contribute to or exacerbate lipid accumulation. PMID- 1643240 TI - DNA associations: packing calculations in A-, B-, and Z-DNA structures. AB - A detailed theoretical study has been carried out to examine the modes of DNA-DNA interactions on the basis of hard-sphere contact criteria. Two helices of identical structure and length are oriented side-by-side and their relative positions are controlled by translations along and rotations about specific axes. Short atomic contacts between pairs of atoms in the structures are assessed and contact-free configurations are compiled. The computed contact-free arrangements of A, B, and Z double helices are found to be remarkably similar to the packing motifs observed in DNA crystals and stretched fibers. Equally interesting in the study are the broad ranges of sterically acceptable arrangements that preserve the overall packing morphology of neighboring duplexes: Among the most notable morphological features in the helical complexes are extended "super" major and minor grooves which might facilitate the wrapping and packaging of DNA chains in supramolecular assemblies. The hard-sphere computations, however, are insufficient for quantitative interpretation of the packing of DNA helices in the solid state. The results are, nevertheless, a useful starting point for energy based studies as well as relevant to the analysis of long-range interactions in DNA supercoils and cruciforms. PMID- 1643241 TI - Biochemical correlates with myocardial aging. AB - Both contraction and relaxation times are prolonged in cardiac muscle of senescent animals. This is in part explained by an alteration of excitation contraction coupling due to an increased duration of the action potential, reduced biosynthesis of the Ca(2+)-stimulated ATPase pump of sarcoplasmic reticulum, and prevalence of the V3 isoform of myosin with slow ATPase activity. The response to catecholamine decreases with aging because of a defective transmission of alpha and beta adrenergic stimulation mediated respectively by phosphoinositide hydrolysis and adenylate cyclase. Cardiac energetics is also impaired in the aged myocardium, since ATP and creatine phosphate levels are reduced by about 20%. This reduction seems in part the consequence of defective mitochondrial function, especially in fatty acid oxidation and ATP translocation to the cytoplasm. In this paper we have discussed the possibility that oxygen free radicals may be a cause of myocardial senescence, by damaging the nuclear and mitochondrial genomes as well as membranes and other cellular components. PMID- 1643242 TI - Reduction of myocardial damage by cloricromene during ischemia-reperfusion in the rabbit. AB - We studied the effect of cloricromene on myocardial damage during ischemia and reperfusion. The left anterior descending coronary artery was occluded in 20 rabbits and cloricromene (6.2 micrograms/kg/min) (n = 10) or placebo (n = 10) were continuously infused. After 10 minutes of occlusion, a first biopsy was obtained from the apex. After 30 minutes, the artery was reopened and after 10 minutes a second biopsy was taken. Both samples were used for chemiluminescence and electron microscopy. The group given placebo showed displacement of the ST segment throughout the ischemic period and arrhythmias during reperfusion; while, in the group given cloricromene, there were transient ST segment elevations in 5 animals, which reverted as the infusion was increased. The chemiluminescence values were 7100 +/- 1300 cpm/mg protein and 14900 +/- 2300 (p less than 0.01) for the first and second biopsies of the control group and 5900 +/- 900 and 6100 +/- 900 (NS) for the first and second biopsies of the cloricromene-treated group. In the group given placebo, the second biopsy showed early signs of irreversible myocyte injury and infarction, whereas samples from the group given cloricromene showed a preservation of myocyte architecture. During ischemia, the percentage of normal mitochondria was lower in the placebo group (p less than 0.0001); and, on reperfusion, the percentage of severely damaged mitochondria was increased in the placebo group (p less than 0.0001). The direct addition of cloricromene in vitro to myocardial homogenates did not reduce hydroperoxide-induced chemiluminescence. PMID- 1643243 TI - 1- and 3-nitro-6-azabenzo[a]pyrenes and their N-oxides: highly mutagenic nitrated azaarenes. PMID- 1643244 TI - Mouse skin tumor initiating activity of fluorinated derivatives of 1,2,3,4 tetrahydro-7,12-dimethylbenz[a]anthracene. PMID- 1643245 TI - Microsomal metabolism of cyclopenta[cd]pyrene. Characterization of new metabolites and their mechanism of formation. AB - Oxidation of cyclopenta[cd]pyrene (CPP) by mouse and human liver microsomes was used to produce several previously undescribed metabolites, which were separated and isolated by reversed-phase HPLC. Three of these, 3,4-dihydroCPP-c-3,4-diol, 4 hydroxy-3,4-dihydroCPP, and 4-oxo-3,4-dihydroCPP, were fully characterized by GC MS and UV spectroscopic analysis as well as by total synthesis. Two additional pairs of metabolites were identified as isomeric tetrahydrotetrols and dihydrotriols by GC-MS analysis of their trimethylsilyl derivatives. Their UV spectra were recorded and found to agree with the structure assignments. The tetrahydrotetrols were further characterized by the fact that either 3,4- or 9,10 trans-dihydrodiol could serve as their precursor, indicating that they are the two diastomeric 3,4,9,10-tetrahydroCPP-t-3,4-t-9,10-tetrols. The dihydrotriols were shown to possess t-3,4-dihydrodiol functionality. As found previously using rat liver microsomes, the most abundant metabolite was 3,4-dihydroCPP-t-3,4-diol. It was produced with one enantiomer in severalfold excess over the other, and the major enantiomer was shown to have 3R,4R configuration by exciton chirality circular dichroism. Microsomal oxidation of [4-2H]CPP, which was synthesized for this study, was used to determine the mechanisms of formation of 4-oxo- and 4 hydroxy-3,4-dihydroCPP. The ketone was produced without detectable retention of deuterium label, eliminating the NIH shift as a possible mechanism. The alcohol was shown to arise by NADPH-dependent reduction of both the ketone and another intermediate presumed to be the 3,4-epoxide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1643246 TI - NADPH-dependent oxidation of reduced ebselen, 2-selenylbenzanilide, and of 2 (methylseleno)benzanilide catalyzed by pig liver flavin-containing monooxygenase. AB - The selenazole ring-opened metabolites of ebselen, 2-selenylbenzanilide and 2 (methylseleno)benzanilide, are substrates for flavin-containing monooxygenase from pig liver. The Km values were 25 and 3 microM, respectively, measured at 37 degrees C, pH 7.4, in the presence of 1 mM GSH. The Vmax values were 390 mU/mg of protein, similar to those obtained with methimazole or other substrates for FMO1. Although ebselen also appears to be a substrate in the absence of GSH, it progressively inactivates the enzyme, apparently by binding covalently to essential enzyme thiols. The oxidation products of the selenol and methylseleno derivatives are rapidly reduced by GSH, regenerating the parent substrates. Rapid reduction of the selenide oxide by GSH was unexpected and suggests that, unlike S oxidation of sulfides, Se-oxidation of selenides may be a route for bioactivation. The data show that in the presence of FMO1 micromolar amounts of either of these ring-opened metabolites establish a futile cycle catalyzing the oxidation of GSH to GSSG by NADPH and oxygen. PMID- 1643247 TI - Arylamination and arylation of 4,4,4-trifluoro-1-phenyl-1,3-butanedione with N acetoxy derivatives of 2-aminofluorene. AB - The present study investigated the reaction of carcinogenic electrophiles with beta-diketones which possess an active methylene group. N-Acetoxy-2 (acetylamino)fluorene bound to tRNA at 37 degrees C, pH 7.0, and this reaction was inhibited by 4,4,4-trifluoro-1-phenyl-1,3-butanedione or 2 thenoyltrifluoroacetone. N-Acetoxy-2-(acetylamino)fluorene reacted with these active methylene compounds to form transitory 3-substituted 2 (acetylamino)fluorene intermediates, which, following cleavage of the trifluoroacetyl group, yielded 3-phenacyl-2-(acetylamino)fluorene or 3-(2 thenoylmethyl)-2-(acetylamino)fluorene. N-Acetoxy-2 [(trifluoroacetyl)amino]fluorene reacted with 4,4,4-trifluoro-1-phenyl-1,3 butanedione to yield two products, N-phenacyl-1-(trifluoroacetyl)-2-aminofluorene and N-phenacyl-3-(trifluoroacetyl)-2-aminofluorene. The ratio of these two products was approximately 1:2. The same N-phenacyl products were produced by incubation of the beta-diketone, N-hydroxy-2-(acetylamino)fluorene, and rat liver cytosol which catalyzed the formation of N-acetoxy-2-aminofluorene. Thus, the inhibitions by beta-diketones of nucleic acid-binding and bacterial mutagenesis of carcinogens are likely due to their trapping of the carcinogens. PMID- 1643248 TI - Oligomerization of indole-3-carbinol in aqueous acid. AB - Indole-3-carbinol [I3C, also called 3-(hydroxymethyl)indole] is a naturally occurring modulator of carcinogenesis with a biological activity that is at least partially dependent on its conversion to active substances in acidic media. We compared the identities of the major oligomeric products of I3C produced under conditions approximating those found in gastric juice with the reported identities of products of 3-substituted indoles produced under enzymatic and other nonenzymatic conditions. After a 10-min treatment in aqueous HCl solution, I3C was converted in 18% yield to a mixture of acetonitrile-soluble products, the major components of which (as determined by HPLC) were diindol-3-ylmethane (5.9%), 5,6,11,12,17,18-hexahydrocyclononal[1,2-b:4,5-b':7,8-b"]triindo le (2.0%), and [2-(indol-3-ylmethyl)indol-3-yl]indol-3-ylmethane (5.9%). Tentative assignments were made for 3,3-bis(indol-3-ylmethyl)indolenine (0.59%), a symmetrical cyclic tetramer (0.64%), and a linear tetramer (1.1%). Indolo[3,2 b]carbazole (ICZ) was formed slowly in aqueous acidic solutions in low yields (2.0 ppm) which increased to greater than 90 ppm following addition of an organic solvent [tetrahydrofuran (THF) or dimethylformamide (DMF)] to a neutralized solution. Relative yields of trimers vs dimer increased with decreasing pH and with decreasing starting concentration of I3C. Evidence is presented that ICZ formation may not involve radical intermediates as is characteristic of photodynamic processes. A mechanistic rationale is presented for the formation of the identified products. PMID- 1643249 TI - Flavin-containing monooxygenase-dependent stereoselective S-oxygenation and cytotoxicity of cysteine S-conjugates and mercapturates. AB - The metabolism of cysteine S-conjugates of both cis- and trans-1,3 dichloropropene in the presence of rat kidney microsomes and purified flavin containing monooxygenase from hog liver was investigated in vitro. Preliminary studies with isolated rat kidney cells demonstrated that cysteine S-conjugates were quite toxic to the cells in a process which was consistent with a role of the flavin-containing monooxygenase in the bioactivation of the nephrotoxins. Putative S-oxide metabolites of cysteine S-conjugates were chemically synthesized, and diastereomers were separated and identified by spectroscopic means. The metabolic products of cysteine S-conjugates were identified by comparing the chemical properties of the metabolites with authentic synthetic cysteine S-conjugate S-oxides. Surprisingly, S-conjugate S-oxygenase activity was not observed with rat kidney microsomes but was present when cysteine S conjugates were incubated with the highly purified flavin-containing monooxygenase from hog liver. The kinetic parameters indicated that considerable S-oxygenase stereoselectivity and structural selectivity was observed: cis cysteine S-conjugates were preferred substrates and N-acetylation of cysteine S conjugates decreased substrate activity. S-Oxygenation was considerably diastereoselective and diastereoselectivity was much greater for cysteine S conjugates with higher Vmax values. Cysteine S-conjugate S-oxides were not indefinitely stable, and under certain conditions, the S-oxides underwent a [2,3] sigmatropic rearrangement to acrolein. Formation of acrolein or other electrophilic products from S-(chloropropenyl)cysteine conjugate S-oxides may contribute to the renal effects observed for S-(chloropropenyl)cysteine conjugates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1643250 TI - Oxidation of aflatoxins and sterigmatocystin by human liver microsomes: significance of aflatoxin Q1 as a detoxication product of aflatoxin B1. AB - Aflatoxin Q1 8,9-oxide was synthesized and found to yield lower levels of N7 guanyl adducts than obtained from aflatoxin B1 8,9-oxide when mixed with calf thymus DNA or Salmonella typhimurium TA 98 cells. However, when S. typhimurium TA 98 was treated with the (analogous) epoxides of aflatoxin B1, aflatoxin G1, aflatoxin Q1, or sterigmatocystin, the ratios of revertants to N7-guanyl DNA adducts were similar. Aflatoxin Q1 and aflatoxin B1 8,9-oxide (trapped here as the glutathione conjugate) are the major oxidative products formed from aflatoxin B1 at all substrate concentrations in human liver microsomes, and cytochrome P 450 (P-450) 3A4 appears to be the dominant enzyme involved in both oxidations, as judged by studies involving correlation of activities in different liver samples, chemical inhibition, immunoinhibition, and reconstitution with purified hepatic and yeast recombinant P-450 3A4. Aflatoxin Q1 is not appreciably oxidized in human liver microsomes and is not very genotoxic. The postulated formation of both aflatoxin Q1 and aflatoxin 8,9-oxide from aflatoxin B1 can be rationalized by a model in which P-450 3A4 binds the substrate in either of two different configurations. This is further demonstrated by the dichotomous effect of 7,8 benzoflavone--this flavone stimulates 8,9-epoxidation while inhibiting the 3 alpha-hydroxylation reaction to form aflatoxin Q1. Thus, the 3 alpha hydroxylation of aflatoxin B1 to aflatoxin Q1 is viewed as a potentially significant detoxication pathway. PMID- 1643251 TI - Mechanism of metabolic activation of the potent carcinogen 7,12 dimethylbenz[a]anthracene. AB - The DNA adducts of 7,12-dimethylbenz[a]anthracene (DMBA) previously identified in vitro and in vivo are stable adducts formed by reaction of the bay-region diol epoxides of DMBA with dG and dA. In this paper we report identification of several new DMBA-DNA adducts formed by one-electron oxidation, including two adducts lost from DNA by depurination, DMBA bound at the 12-methyl to the N-7 of adenine (Ade) or guanine (Gua) [7-methylbenz[a]anthracene (MBA-12-CH2-N7Ade or 7 MBA-12-CH2-N7Gua, respectively]. The in vitro systems used to study DNA adduct formation were DMBA activated by horseradish peroxidase or 3-methyl-cholanthrene induced rat liver microsomes. The biologically-formed depurination adducts were identified by high-pressure liquid chromatography and by fluorescence line narrowing spectroscopy. Stable DMBA-DNA adducts were analyzed by the 32P postlabeling method. Quantitation of DMBA-DNA adducts formed by microsomes showed about 99% as depurination adducts: 7-MBA-12-CH2-N7Ade (82%) and 7-MBA-12-CH2 N7Gua (17%). Stable adducts (1.4% of total) included one adduct spot that may contain adduct(s) formed from the diol epoxide (0.2%) and unidentified adducts (1.2%). Activation of DMBA by horseradish peroxidase afforded 56% of stable unidentified adducts and 44% of depurination adducts, with 36% of 7-MBA-12-CH2 N7Ade and 8% of 7-MBA-12-CH2-N7Gua. Adducts containing the bond to the DNA base at the 7-CH3 group of DMBA were not detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1643252 TI - Formation of mitochondrial phospholipid adducts by nephrotoxic cysteine conjugate metabolites. AB - Nephrotoxic cysteine conjugates derived from a variety of halogenated alkenes are enzymatically activated via the beta-lyase pathway to yield reactive sulfur containing metabolites which bind covalently to cellular macromolecules. Mitochondria contain beta-lyase enzymes and are primary targets for binding and toxicity. Previously, mitochondrial protein and/or DNA have been considered as molecular targets for cysteine conjugate metabolite binding. We now report that metabolites of nephrotoxic cysteine conjugates form covalent adducts with rat kidney mitochondrial phospholipids. Rat kidney mitochondria were incubated with the 35S-labeled conjugates S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC), S-(2 chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC), S-(1,2-dichlorovinyl)-L-cysteine, and S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine. Quantitation of metabolite binding to whole mitochondria and to mitochondrial protein and lipid fractions revealed that as much as 42% of the 35S-label associated with the mitochondria was found in the lipid fraction. Total lipids were also extracted from 35S treated mitochondria and separated by thin-layer chromatography. 35S-Containing metabolites were found in the lipid fractions from mitochondria treated with each of the conjugates. Lipids from both [35S]CTFC- and [35S]-TFEC-treated mitochondria contained major 35S-labeled lipid adducts which had similar mobility by thin-layer chromatography. Fatty acid analysis, 19F and 31P NMR spectroscopy, and mass spectrometric analyses confirmed that the major TFEC and CTFC adducts are thioamides of phosphatidylethanolamine. PMID- 1643253 TI - Comparative tumorigenicity of dimethylchrysenes in mouse skin. AB - In previous studies, we have observed unexpected structure-tumorigenicity relationships among the dimethylchrysenes. Thus, 5,6-dimethylchrysene and 5,7 dimethylchrysene were only weakly tumorigenic and were significantly less active than 5-methylchrysene. These results were surprising in view of the known route of metabolic activation of 5-methylchrysene via its 1,2-diol 3,4-epoxide. In this paper, we extended our studies of structure-tumorigenicity relationships among the dimethylchrysenes. We synthesized 5,7-, 5,8-, 5,9-, and 5,10-dimethylchrysene via photochemical ring closure reactions. The tumor-initiating activities of these dimethylchrysenes on mouse skin were compared with those of 5 methylchrysene and 5,6-dimethylchrysene. 5-Methylchrysene and 5,9 dimethylchrysene were highly tumorigenic and were significantly more active than 5,6-, 5,7-, 5,8-, and 5,10-dimethylchrysene. The results of these studies, taken together with those reported in the subsequent two papers, suggest that the molecular shapes of dimethylchrysenes influence the balance between metabolic activation and detoxification pathways. PMID- 1643254 TI - Metabolism and DNA binding of 5,6-dimethylchrysene in mouse skin. AB - 5,6-Dimethylchrysene (5,6-diMeC) is a weaker tumor initiator on mouse skin than 5 methylchrysene (5-MeC). To investigate the reasons for the unexpectedly low activity of 5,6-diMeC, we have studied its metabolism and DNA binding in mouse skin, particularly with respect to metabolic activation via its anti-1,2-diol 3,4 epoxide. The metabolism of 5,6-diMeC was first examined with liver 9000g supernatant from Aroclor 1254 pretreated rats. Three major metabolites were identified as 1- or 7-hydroxy-5-(hydroxymethyl)-6-MeC, 1,2-dihydroxy-1,2-dihydro 5,6-diMeC (5,6-diMeC-1,2-diol), and 1-hydroxy-5,6-diMeC. The formation of 5,6 diMeC-1,2-diol was then assessed in mouse epidermis, following topical application of [3H]5,6-diMeC. Levels of 5,6-diMeC-1,2-diol in epidermis exceeded those of 5-MeC-1,2-diol formed from 5-MeC under similar conditions. The binding of [3H]5,6-diMeC and that of [3H]5-MeC to mouse epidermal DNA were then compared. 5,6-DiMeC-deoxyribonucleoside adducts were prepared as markers by reaction of anti- and syn-5,6-diMeC-1,2-diol 3,4-epoxide with calf thymus DNA. HPLC analysis of enzymatic hydrolysates of mouse epidermal DNA, isolated 18 h after topical treatment with [3H]5,6-diMeC or [3H]5-MeC, demonstrated the formation from [3H]5,6-diMeC of two major adducts produced by reaction of its anti-1,2-diol 3,4 epoxide with deoxyguanosine and deoxyadenosine, respectively, while the major adduct formed from [3H]5-MeC resulted from reaction with deoxyguanosine, in agreement with previous results. Total DNA binding of [3H]5-MeC as well as formation of deoxyguanosine adducts exceeded that of [3H]5,6-diMeC by 3-4 fold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1643255 TI - Dimethylchrysene diol epoxides: mutagenicity in Salmonella typhimurium, tumorigenicity in newborn mice, and reactivity with deoxyadenosine in DNA. AB - In contrast to 5-methylchrysene and 5,9-dimethylchrysene, 5,6-dimethylchrysene and 5,7-dimethylchrysene are weak tumor initiators on mouse skin. In order to investigate the basis for this, we have evaluated the mutagenic activities toward Salmonella typhimurium TA 100 and reactivity with DNA of (+/-)-anti-1,2-dihydroxy 3,4-epoxy-1,2,3,4-tetrahydro-5,6-dimethyl-ch rys ene (anti-5,6-diMeC-1,2-diol 3,4 epoxide) and anti-5,7- and anti-5,9-diMeC-1,2-diol 3,4-epoxide. The tumorigenic activities of anti-5,6- and anti-5,7-diMeC-1,2-diol 3,4-epoxides in newborn mice were also investigated. anti-5,9-diMeC-1,2-diol 3,4-epoxide was the most mutagenic of the three diol epoxides. anti-5,6-diMeC-1,2-diol 3,4-epoxide was highly tumorigenic in newborn mouse lung, with activity significantly greater than that of either anti-5-MeC- or anti-5,7-diMeC-1,2-diol 3,4-epoxide. Although the amounts of total binding of the diol epoxides to calf thymus DNA were similar, anti-5,6-diMeC-1,2-diol 3,4-epoxide bound extensively to deoxyadenosine residues. High binding to deoxyadenosine is related to the presence of a sterically hindered bay or fjord region as present in 5,6-diMeC, 7,12 dimethylbenz[a]anthracene, benzo-[g]chrysene, and benzo[c]phenanthrene. The conformations of the anti- and syn-diol epoxides of 5,6-diMeC and benzo[c]phenanthrene were similar, with both having pseudodiequatorial hydroxyl groups, in contrast to less sterically crowded diol epoxides. The high tumorigenicity of anti-5,6-diMeC-1,2-diol 3,4-epoxide in newborn mice is of interest with respect to its high deoxyadenosine binding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1643256 TI - Covalent cross-linking of proteins by carbon disulfide. AB - Carbon disulfide is known to react with amino groups of proteins to generate dithiocarbamates (2). We observed covalent cross-linking of dithiocarbamate derivatized proteins under physiological conditions which may occur through several mechanisms. Evidence for the structure of these covalent bridges and the reactive intermediate was obtained using 13C NMR spectroscopy in conjunction with specific isotopic labeling. On incubation at 37 degrees C oxidative coupling of dithiocarbamates generated bis(thiocarbamoyl) disulfides (3) which were reduced by cysteine. In addition, an electrophilic isothiocyanate (4) was generated from decomposition of the dithiocarbamate. Nucleophilic addition of sulfhydryl and amine moieties to the isothiocyanate produced dithiocarbamate ester (5) and thiourea linkages (6), respectively. Evidence for the presence of inter- and intramolecular cross-links was obtained using denaturing polyacrylamide gel electrophoresis under reducing conditions. The formation of isothiocyanate in neutral solution, through elimination of sulfhydryl ion, was correlated with increased pKa values of the parent amine of amino acids. Dithiocarbamates derived from terminal amino groups of proteins did not appear to generate isothiocyanate or form thiourea or dithiocarbamate ester. Both the thiourea and the dithiocarbamate ester were stable at reduced pH, whereas in alkaline media the thiourea was stable but dithiocarbamate ester was hydrolyzed. Although the disulfide and ester linkages were formed more rapidly than the thiourea, generation of the latter appeared to be irreversible, leading to its gradual accumulation over a longer period of time. Generation of isothiocyanate by CS2 derived dithiocarbamates and subsequent covalent cross-linking of proteins may provide a molecular mechanism for CS2-induced axonopathy. PMID- 1643257 TI - Experimental and theoretical study on the redox cycling of resorufin by solubilized and membrane-bound NADPH-cytochrome reductase. AB - The present study describes both experimental and theoretical data on the redox cycling of resorufins catalyzed by NADPH-cytochrome reductase. At 1-5 microM concentrations at physiological pH, the redox cycling of ethoxy- and pentoxyresorufin was shown to be far more efficient than the redox cycling of their product from the cytochrome P-450 dependent O-dealkylation, resorufin (7 hydroxyphenoxazone). This was shown to result from the fact that (i) the protonated form of the resorufin is a much better substrate for redox cycling than the deprotonated resorufin O-anion and (ii) at physiological pH the redox cycling active protonated form is present at only 1-4% of the total amount of resorufin. In addition to experimental data, AM1 molecular orbital computer calculations provided evidence for the difference in redox cycling capacity between the resorufin O-anion and its protonated form. The energy of the lowest unoccupied molecular orbital (ELUMO) of the resorufin O-anion is higher than the ELUMO value for the protonated form. This low ELUMO value of the protonated form can be taken as a parameter for its easier reduction. Furthermore, computer calculations demonstrated one-electron reduction of the protonated form to be energetically favorable by 363.5 kJ/mol, compared to one-electron reduction of the deprotonated O-anionic form. Additional AM1 molecular orbital computer calculations indicated that the one-electron-reduced resorufin will become protonated at the O-atom of the intramolecular semiquinone imine moiety before reduction by a second electron becomes likely. Finally, redox cycling of resorufin by solubilized and membrane-incorporated NADPH-cytochrome reductase provided evidence that membrane surroundings increase the concentration of the protonated form of resorufin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1643258 TI - Effect of bovine serum albumin on the extent of ortho rearrangement of N (sulfooxy)-2-fluorenylacetamide and of enzymatically activated N-hydroxy-2 fluorenylacetamide and on the binding of reactive esters to nucleic acids. AB - We have investigated the effect of the bovine serum albumin (BSA)-catalyzed ortho rearrangement of synthetic and enzymatically generated N-(sulfooxy)-2 fluorenylacetamide (NSF) to the O-sulfate esters on the binding of NSF to transfer ribonucleic acid (tRNA) and to deoxyribonucleic acid (DNA). Binding of synthetic NSF to tRNA and DNA decreased approximately 90 and 70%, respectively, in the presence of BSA. Under these conditions, the ortho rearrangement, a minor reaction in the absence of BSA, was nearly quantitative. The decrease of adduct formation to nucleic acids was not attributable to the competitive binding of NSF to BSA. Binding of NSF, generated by cytosolic sulfonation of the arylhydroxamic acid, N-hydroxy-2-fluorenylacetamide, to tRNA, was diminished approximately 97% in the presence of BSA while the ortho rearrangement of the sulfonated substrate increased from less than 0.5% to approximately 50%. Adduct formation of DNA with N-hydroxy-2-fluorenylacetamide, activated by enzymatic sulfonation, was inhibited approximately 90% in the presence of BSA. In these experiments, the catalytic effect of BSA on the ortho rearrangement of enzymatically sulfonated N-hydroxy-2 fluorenylacetamide was of the same order as observed in the experiments with tRNA. The data obtained on the covalent interaction of DNA with enzymatically activated N-hydroxy-2-fluorenylacetamide indicate that, in addition to NSF, another electrophilic species accounts for binding of activated N-hydroxy-2 fluorenylacetamide to DNA. The data support the view that the reactive electrophile is N-acetoxy-2-fluorenamine, resulting from the N,O-transacetylation of N-hydroxy-2-fluorenylacetamide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1643259 TI - Characterization of the glucuronide conjugate of cotinine: a previously unidentified major metabolite of nicotine in smokers' urine. AB - Recent studies in our laboratories have confirmed that a major unidentified metabolite of nicotine in smokers' urine was susceptible to enzymatic degradation by beta-glucuronidase to afford (S)-(-)-cotinine. In order to establish the identity of this metabolite, the quaternary ammonium conjugate, viz., (S)-(-) cotinine N-glucuronide, was synthesized. Reaction of methyl 2,3,4-tri-O-acetyl-1 bromo-1-deoxy-alpha-D-glucopyranuronate with (S)-(-)-cotinine at 60 degrees C for 3 days affords the fully protected conjugate as the bromide salt. Deprotection was accomplished in 1 M NaOH overnight at 25 degrees C. The deprotected inner salt was isolated by Dowex-50W cation-exchange chromatography. Electrospray mass spectra of the inner salt revealed the presence of ions with m/z 353 (M + H)+, 375 (M + Na)+, and 391 (M + K)+ as well as ions resulting from loss of water and cleavage of the glycosidic bond. Proton and carbon nuclear magnetic resonance spectra established that the position of glucuronidation was the pyridyl nitrogen. The magnitude of the coupling between H1" and H2" of the sugar ring (8.71 Hz) and nuclear Overhauser enhancements were consistent with the beta isomer of the glucuronide conjugate. The synthetic (S)-(-)-cotinine N-glucuronide was susceptible to enzymatic hydrolysis by beta-glucuronidase to afford (S)-(-) cotinine. Application of a cation-exchange high-performance liquid chromatographic method enabled the collection of a fraction containing (S)-(-) cotinine N-glucuronide from a smoker's urine. The electrospray mass spectrum of this fraction contained ions consistent with the presence of (S)-(-)-cotinine N glucuronide. The concentrated fraction was subjected to enzymatic hydrolysis by beta-glucuronidase to afford (S)-(-)-cotinine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1643260 TI - Epoxide ring opening and related reactivities of cyclopenta polycyclic aromatic hydrocarbons: quantum mechanical studies. AB - A series of 13 cyclopenta polycyclic aromatic hydrocarbons have been studied using quantum mechanical methods. The three-dimensional molecular structure of each carbocation that might result from the opening of a protonated epoxide ring formed between the carbon atoms completing the cyclopenta ring was computed with AM1. AM1 and ab initio calculations, using a split valence basis set, were then used to predict the direction of ring opening and obtain information about the reactivity of the carbocation. These calculations have shown that for all carbocations studied the cationic charge is well distributed throughout the molecule. The largest CH group charges are approximately 0.3 electron. If the protonated epoxide ring can open so that the nominal charge is on a CH group that is attached to the central ring of an anthracenic core, that carbocation will be greatly favored. For carbocations of this type, the unoccupied alpha' position (the CH group opposite the position of attachment to the anthracenic core) has as much or more of the cation charge as the nominally charged CH position. The group charges, and other properties related to electrostatic reactivity, clearly favor addition of nucleophiles at the unoccupied alpha' position over addition at the nominally charged position. However, when the addition of small nucleophiles at both of these positions is modeled for two such examples, the results favor addition at the nominally charged position in one case and are equivocal in the other case. The group charges and other reactivities considered characterize the electrostatic part of the interaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1643261 TI - Model adducts of benzo[a]pyrene and nucleosides formed from its radical cation and diol epoxide. AB - Reference adducts formed by reaction of deoxyribonucleosides with the ultimate carcinogenic forms of benzo[a]pyrene (BP), BP radical cation and BP diol epoxide, are essential for identifying the structures of adducts formed in biological systems. Electrochemical oxidation of BP in the presence of dG or dA produces adducts from BP radical cation. When 8 equiv of charge are consumed, four adducts are formed with dG: 7-(BP-6-yl)Gua, 8-(BP-6-yl)Gua, N2-(BP-6-yl)dG and 3-(BP-6 yl)dG. With 2 equiv of charge, however, only 7-(BP-6-yl)Gua and 8-(BP-6-yl)dG (BP 6-C8dG) are formed. Anodic oxidation of BP-6-C8dG affords 8-(BP-6-yl)Gua. Anodic oxidation of BP in the presence of dA produces 7-(BP-6-yl)Ade. Reaction of BP diol epoxide with dG yields 10-(guanin-7-yl)-7,8,9-trihydroxy-7,8,9,10 tetrahydroBP, whereas reaction with dA affords three adducts, 10-(adenin-7-yl) 7,8,9-trihydroxy-7,8,9,10-tetrahydroBP and two isomers of 10-(deoxyadenosin-N6 yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydroBP . On the basis of comparative kinetic studies among adducts of aromatic hydrocarbons and dG or G, only BP-6-C8dG easily loses the sugar moiety, providing a basis for a mechanism of hydrolysis of the glycosidic bond. PMID- 1643262 TI - Identification and quantitation of benzo[a]pyrene-DNA adducts formed by rat liver microsomes in vitro. AB - The two DNA adducts of benzo[a]pyrene (BP) previously identified in vitro and in vivo are the stable adduct formed by reaction of the bay-region diol epoxide of BP (BPDE) at C-10 with the 2-amino group of dG (BPDE-10-N2dG) and the adduct formed by reaction of BP radical cation at C-6 with the N-7 of Gua (BP-6-N7Gua), which is lost from DNA by depurination. In this paper we report identification of several new BP-DNA adducts formed by one-electron oxidation and the diol epoxide pathway, namely, BP bound at C-6 to the C-8 of Gua (BP-6-C8Gua) and the N-7 of Ade (BP-6-N7Ade) and BPDE bound at C-10 to the N-7 of Ade (BPDE-10-N7Ade). The in vitro systems used to study DNA adduct formation were BP activated by horseradish peroxidase or 3-methylcholanthrene-induced rat liver microsomes, BP 7,8 dihydrodiol activated by microsomes, and BPDE reacted with DNA. Identification of the biologically-formed depurination adducts was achieved by comparison of their retention times on high-pressure liquid chromatography in two different solvent systems and by comparison of their fluorescence line narrowing spectra with those of authentic adducts. The quantitation of BP-DNA adducts formed by rat liver microsomes showed 81% as depurination adducts: BP-6-N7Ade (58%), BP-6-N7Gua (10%), BP-6-C8Gua (12%), and BPDE-10-N7Ade (0.5%). Stable adducts (19% of total) included BPDE-10-N2dG (15%) and unidentified adducts (4%). Microsomal activation of BP 7,8-dihydrodiol yielded 80% stable adducts, with 77% as BPDE-10-N2dG and 20% of the depurination adduct BPDE-10-N7Ade. The percentage of BPDE-10-N2dG (94%) was higher when BPDE was reacted with DNA, and only 1.8% of BPDE-10-N7Ade was obtained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1643263 TI - Perturbation of peptide conformations induced in anisotropic environments. AB - Reversed-phase high performance liquid chromatography (RP HPLC) has been found to be a convenient and powerful tool for the study of the secondary structure of peptides. Here, the ability of proline to perturb the secondary structures of peptides induced at aqueous-lipid interfaces and the induced conformation of polyproline peptides were investigated by means of RP HPLC. For these studies, four different complete sets of substitution analogues of model peptides expected to have specific induced conformations were used. In the first two studies, a single lysine was "walked" through two 18-residue polyproline sequences (one N acetylated, the other not). In the remaining two studies, a proline was "walked" through two different sequences that had been found earlier to be induced into an alpha-helical conformation during RP HPLC (an 18-residue polyalanine sequence and the amphipathic 14-residue sequence Ac-LLKLLKKLLKKLKK-NH2). Sixty-eight individual analogues were synthesized for this study and the effect of the respective substitutions on retention times was determined. The results are consistent with the concept that, upon interaction with the C-18 of the stationary phase during RP HPLC, polyproline is induced into a type II helical conformation, polyalanine into an alpha-helical conformation, and Ac LLKLLKKLLKKLKK-NH2 into an amphipathic alpha-helical array. In an extension of this study, the antimicrobial activities of Ac-LLKLLKKLLKKLKK-NH2 and its 18 proline substitution analogues were found to be inversely correlated with their RP HPLC retention times. PMID- 1643264 TI - Heavy metal binding to heparin disaccharides. I. Iduronic acid is the main binding site. AB - As model compounds for Ni(II)-binding heparin-like compounds isolated from human kidneys (Templeton, D.M. & Sarkar, B. (1985) Biochem. J. 230 35-42.), we investigated two disaccharides--4-O-(2-O-sulfo-alpha-L-idopyranosyluronic acid) 2,5-anhydro- D-mannitol, disodium salt (1a), and 4-O-(2-O-sulfo-alpha-L idopyranosyluronic acid)-6-O- sulfo-2,5-anhydro-D-mannitol, trisodium salt (1b)- that were isolated from heparin after nitrous acid hydrolysis and reduction. The monosulfate (1a) was active whereas the disulfate (1b) was inactive in a high performance liquid chromatography (HPLC) binding assay with the tracer ions 63Ni(II) 54Mn(II), 65Zn(II), and 109Cd(II). This result is in accord with the isolation of two 67Cu(II) and 63Ni(II) binding fractions from a complete pool of nitrous-acid-derived heparin disaccharides using sulfate gradients and a MonoQ anion exchange column on an FPLC system. One was identified as compound (1a) and the other as a tetrasulfated trisaccharide by high resolution FAB-MS, NMR and HPLC-PAD. Similarly, two synthetic disaccharides-methyl, 2-O-sulfo-4-O-(alpha-L idopyranosyluronic acid)-2-deoxy-2-sulfamide-alpha-D-glucosamine, trisodium salt [IdopA2S(alpha 1,4)GlcNS alpha Me, 2a], and 2-O-sulfo-4-O-(alpha-L idopyranosyluronic acid)-2-deoxy-2-sulfamide-6-O-sulfo- alpha-D-glucosamine, tetrasodium salt [IdopA2S (alpha 1,4)GlcNS6S alpha Me, 2b]--were shown to bind tracer amounts of 63Ni and 67Cu using chromatographic assays. Subsequently, 1H NMR titrations of 1a, 1b, 2a, and 2b with Zn (OAc)2 were analyzed to yield 1:1 Zn(II)-binding constants of 472 +/- 59, 698 +/- 120, 8,758 +/- 2,237 and 20,100 +/- 5,598 M-1, respectively. The values for 2a and 2b suggest chelation. It is suggested that the idopyranosiduronic acid residue is the major metal binding site. NMR evidence for this hypothesis comes from marked 1H and 13C chemical shift changes to the iduronic acid resonances after addition of diamagnetic Zn(II) ions. PMID- 1643265 TI - Heavy metal binding to heparin disaccharides. II. First evidence for zinc chelation. AB - To map out the heavy metal binding sites of iduronic acid containing oligosaccharides isolated from human kidneys, we studied Zn(II) binding by nuclear magnetic resonance (NMR) and molecular modeling to two disaccharides isolated after nitrous acid depolymerization of heparin and two synthetic disaccharides representative of the heparin structure, namely, IdopA2S (alpha 1,4)AnManOH, 1 alpha, IdopA2S (alpha 1,4)AnManOH6S, 1b, IdopA2S-(alpha 1,4)GlcNS alpha Me, 2a, and IdopA2S (alpha 1,4)GlcNS6S alpha Me, 2b (see previous article in this series). A conformational analysis of the metal free and metal bound solutions was made by comparing calculated [(NOE)]s, [T1]s, and [J]s to experimental values. The 1C4, 4C1, and 2S0 conformations of the L idopyranosiduronate ring and the 4E and 4T3 of the anhydro-D-mannitol ring are evaluated as are rotations about the C5-C6 hydroxymethylene of the AnManOH(6S) or GlcNS (6S) residues. The NOE between IdopA2S H1 and H3 and the known NOE between H2 and H5, as well as the T1 of IdopA2S H3, are introduced as NMR observables sensitive to the IdopA2S ring conformation. Similarly, a NOE between IdopA2S H5 and AnManOH(6S) or GlcNS(6S) H3 was observed that directly restricts the allowed interglycosidic conformational space. For all disaccharides, the Zn(II) bound spectral data are consistent with models in which these motions are partially "frozen" such that the 1C4 conformation of the IdopA2S is stabilized along with the 4T3 conformation of the AnManOH(6S) ring. The interglycosidic conformation is also stabilized in one of two minima. Electrostatic potential energy calculations gave the best overall agreement with experiment and suggest metal binding conformations with the carboxylate and ring oxygen of the IdopA2S residues (1C4 conformation) and either O3 of the GlcNS(6S) residues or the sulfate oxygens of the 6-sulphate for 2b providing additional chelating sites. These chelation models concur with the observation of marked 13C and 1H NMR chemical shifts for the IdopA2S resonances and of GlcNS H3 for 2 alpha and GlcNS6S C6 for 2b. This study of model compounds implicates the IdopA2S(alpha 1,4)GlcNS6S group as part of the heavy metal binding site in biologically important acidic oligosaccharides such as heparin. PMID- 1643266 TI - A molecular mechanical study of the structure of poly(alpha-aminoisobutyric acid). AB - A molecular mechanical study has been carried out to determine the most favorable conformation of poly(Aib) both in solution and in the solid state. An energetic approach to the packing has been carried out by studying the stability of pairs of poly(Aib) chains. The study reveals a higher stability of a 3(10)-helix when forming part of a dimer whereas in isolated molecules the alpha-helix structure seems to be more stable depending on the length of the chain and dielectric constant of the environment. PMID- 1643267 TI - Crystal structure of a helical oligopeptide model of polyglycine II and of other polyamides: acetyl-(glycyl-beta-alanyl)2-NH propyl. AB - We synthesized and solved the crystalline structure of the oligopeptide acetyl (glycyl-beta-alanyl)2-NH propyl. The crystal is formed by layers of helical molecules with the same chirality; however, right-handed layers alternate with left-handed ones. Inside every layer, the packing of helices is pseudohexagonal with hydrogen bonds between neighbor molecules. The structure found affords direct support for the model proposed by Crick and Rich for polyglycine II and also provides an interpretation for the structure of a newly found family of polyamides that do not form sheets as observed in most nylon structures. PMID- 1643268 TI - Solution structures of cyclic and dicyclic analogues of growth hormone releasing factor as determined by two-dimensional NMR and CD spectroscopies and constrained molecular dynamics. AB - Solution structures were determined for a linear analogue of growth hormone releasing factor (GRF), and cyclic and dicyclic analogues in which the side chains of aspartyl and lysyl residues spaced at positions i-(i + 4) were joined to form a lactam. The four analogues were [Ala15]-GRF-(1-29)-NH2 and its cyclo8 12, cyclo21-25, and dicyclo8-12;21-25 derivatives. The peptides were studied in two solvent systems: 75% methanol/25% water at pH 6.0; and 100% water at pH 3.0. CD spectroscopy was used to assess the overall alpha-helical content. Nuclear magnetic resonance spectroscopy was used to determine the structures in more detail. Nearly complete proton resonance assignments were made for each of the peptides, in both solvents. Nuclear Overhauser effects were converted into distance constraints and applied in the molecular dynamics program CHARMM to evaluate the range of low-energy structures that satisfied the nmr data. In 75% methanol, all of the peptides are comprised of a single alpha-helical segment with fraying of one to three residues at each end. The linear analogue has a tendency to kink. In water, the analogues have two helical segments with flexible regions between them and at the termini of the peptides. The linear analogue is helical at residues 7-14 and 21-28. In the cyclo8-12 analogue, the N-terminal helical region extends to include residues 7-19, while the other helical region is slightly shortened. In the cyclo21-25 analogue, the C-terminal helical region is extended to include residues 19-28, while the N-terminal helical region is destabilized. The dicyclic analogue has the largest N-terminal helix, spanning residues 7-20, but its helical segment at residues 21-28 is not well ordered. All of the analogues exhibit substantial biological activity. The cyclic and dicyclic analogues show dramatically increased resistance to degradation during incubation with human plasma. The i-(i + 4) lactam, therefore, appears to be a synthetic means of stabilizing a local alpha-helical conformation, which may be of general use in the design of active, stable peptides. PMID- 1643269 TI - Protein: nucleic acid interactions. I. Electronic structures of cytosine, indole, and guanine complexes. AB - Low singlet transition energies and line strengths were calculated for the cytosine:indole:guanine complex by the INDO/1S-CI method. The chromophores were arranged in three sets of 270 intercalating geometries. Calculations were executed in the supermolecule model with single excited configurations. Errors due to basis set extension and incomplete configuration representation were assessed, for all chromophore pairs, by full BSSE correction calculations and inclusion of double-excited configurations. The intercalation-induced perturbations of the principal transitions are characterized by but not limited to (a) a decrease in strength of [pi*,pi] transitions, (b) increase in strength in [pi*,n] transitions, (c) splitting of [pi*,pi] transitions into components of unequal strength, and (d) energy and strength dependence in mixed transitions on rise and shift movements of the nucleic acid bases. These predictions are in accord with absorption, fluorescence emission, and scattering, and resonance Raman spectroscopic data on oligonucleotides and analogous aromatic complexes. The calculations suggest that major differences in intercalating coordinations are discernible in the near-uv spectroscopic domain of proteins and nucleic acids. PMID- 1643270 TI - The nature of folded states of globular proteins. AB - We suggest, using dynamical simulations of a simple heteropolymer modelling the alpha-carbon sequence in a protein, that generically the folded states of globular proteins correspond to statistically well-defined metastable states. This hypothesis, called the metastability hypothesis, states that there are several free energy minima separated by barriers of various heights such that the folded conformations of a polypeptide chain in each of the minima have similar structural characteristics but have different energies from one another. The calculated structural characteristics, such as bond angle and dihedral angle distribution functions, are assumed to arise from only those configurations belonging to a given minimum. The validity of this hypothesis is illustrated by simulations of a continuum model of a heteropolymer whose low temperature state is a well-defined beta-barrel structure. The simulations were done using a molecular dynamics algorithm (referred to as the "noisy" molecular dynamics method) containing both friction and noise terms. It is shown that for this model there are several distinct metastable minima in which the structural features are similar. Several new methods of analyzing fluctuations in structures belonging to two distinct minima are introduced. The most notable one is a dynamic measure of compactness that can in principle provide the time required for maximal compactness to be achieved. The analysis shows that for a given metastable state in which the protein has a well-defined folded structure the transition to a state of higher compactness occurs very slowly, lending credence to the notion that the system encounters a late barrier in the process of folding to the most compact structure. The examination of the fluctuations in the structures near the unfolding----folding transition temperature indicates that the transition state for the unfolding to folding process occurs closer to the folded state. PMID- 1643271 TI - The use of Flory-Huggins theory in interpreting partitioning of solutes between organic liquids and water. AB - Solute partitioning data for dilute solutions have almost invariably been interpreted by equating experimental values of -RT in Kx (wherein Kx is the mole fraction partition coefficient) to delta mu infinity, the standard Gibbs energy change for solute transfer from one solvent to another. Recently, it has been alleged that this relation is insufficiently general. Instead, the statistical mechanical Flory-Huggins (FH) theory has been recommended for use, because it is designed to account for disparities in molecular size between solute and solvent. Our examination of the thermodynamics of partitioning shows that: (1) The customary interpretation is not only entirely correct (providing only that the solute is dilute), but is model-independent. (2) The dilute limit of the FH theory is seen to agree entirely with the usual interpretation of -RT in Kx, once certain misnomers are cleared away. (3) The use of FH theory being urged upon us in fact serves only to extract from delta mu infinity (the latter quite correctly determined as -RT in Kx) the contact part of delta mu infinity in order to obtain information on hydrophobic interactions. Some caveats are cited concerning such use of the FH statistical mechanical model. PMID- 1643272 TI - Existence of lipid vesicles containing platelet-activating factor in endothelial cell lysate. AB - Platelet aggregation activity due to platelet-activating factor (PAF) was detected at high molecular weight (HMW) and low molecular weight fractions after gel-filtration chromatography of cell lysate of endothelial cells. [3H]PAF added to the cell lysate was similarly distributed after chromatography. The radioactivity associated with HMW fraction was not reduced by digesting the lysate with trypsin, suggesting that PAF was not making complexes with proteins but was included in lipid vesicles in cell lysate. Further evidence showed that an unknown specific factor(s) was needed to form these PAF-containing lipid vesicles. Radioactivity was not found in HMW fraction when [3H]PAF was mixed with cell lysate of vascular smooth muscle cells. When monomeric PAF was added to endothelial cell lysate, the specific activity of aggregation decreased to the level exerted by endogenous PAF-containing lipid vesicles due to incorporation into lipid vesicles. PAF in the form of lipid vesicles was more stable in plasma than monomeric form. PMID- 1643273 TI - Insulin antagonizes the phagocytosis stimulating action of histamine in Tetrahymena. AB - Histamine increased specifically the phagocytic activity of the unicellular Tetrahymena, whereas insulin had no influence on it. Insulin antagonized the phagocytosis stimulating action of histamine after simultaneous exposure and after preexposure two days earlier as well, although in the latter case to a lesser degree. Double exposure to a combination of histamine+insulin didn't influence the phagocytic activity at all, demonstrating the histamine antagonizing effect of insulin in this model. PMID- 1643274 TI - Inhibition of protein N-glycosylation has no effect on the binding of acetyl LDL to J774 cells. AB - Acetyl-LDL (Ac-LDL) bound to transformed mouse macrophage J774 cells in a high affinity, saturable and specific manner. When cells were cultured for 24h in the presence of tunicamycin such that incorporation of N-linked sugars into protein but not protein synthesis itself was inhibited significantly, the binding characteristics of Ac-LDL to the cells were unaltered. In this respect the Ac-LDL receptor of J774 cells is similar to the asialoglycoprotein receptor of HepG2 cells. PMID- 1643275 TI - Changes in alanine and glutamine transport during rat red blood cell maturation. AB - Alanine and glutamine transport have been studied during red blood cell maturation in the rat. Kinetic parameters of Na(+)-dependent L-alanine transport were: Km 0.43 and 1.88 mM and Vmax 158 and 45 nmoles/ml ICW/min for reticulocytes and erythrocytes, respectively. During red cell maturation in the rat there is a loss of capacity and affinity of the system ASC for L-alanine transport. The values for Na(+)-dependent L-glutamine transport in reticulocytes were Km 0.51 mM and Vmax 157 nmoles/ml ICW/min. On the other hand, a total loss of L-glutamine transport mediated by both N and ASC systems is demonstrated in mature red cells. This seems to indicate that during rat red cell maturation the system N disappears. Furthermore, the system ASC specificity in mature cells changes, and glutamine enters the red cell by non-mediated diffusion processes. PMID- 1643276 TI - Surface heterogeneity of rat sperm during maturation. AB - Rat sperm isolated from the caput and caudal epididymis and the vas deferens were subjected to multiple partition in aqueous two-phase systems. The technique was used to reveal heterogeneity of a sperm population with respect to particular surface properties. Sperm from all three regions gave broad distributions indicative of heterogeneous cell populations. Greatest heterogeneity was observed for cauda sperm with caput and vas sperm producing similar distributions. Following multiple partition sperm from different regions of the distribution profiles were immunostained with three antibodies known to recognise maturation antigens. The results show that some antigens are acquired during epididymal transit whilst others are present throughout. The partition (surface heterogeneity) seen cannot therefore be explained solely by the distribution of the antigens recognized by 2D6, 6B2 and 3D5. PMID- 1643277 TI - 2-Ketoisocaproate transport in insulin-secreting cells. AB - The transport of the nutrient secretagogue 2-ketoisocaproate (KIC) was studied in isolated rat pancreatic islets and in the HIT-T15 insulinoma cell line using an oil-filtration technique. In both islets and HIT-T15 cells, KIC uptake was a slow process, not reaching equilibrium within 10 min KIC transport was not dependent upon Na+ in the medium, was not inhibited by alpha-cyano-4-hydroxycinnamate nor by 2-amino-2-norborane carboxylic acid (BCH) and did not appear to be electrogenic. Evidence was obtained to suggest that KIC uptake occurred via passive diffusion into the cell of the undissociated acid species. This possibility was supported by the apparent unsaturability of KIC uptake in HIT-T15 cells. Addition of 10-30 mM KIC to dispersed islets cells or HIT-T15 cells produced a rapid intracellular acidification. In islets, the rate of transport of 10 mM KIC was comparable with oxidation rate of the keto-acid suggesting that uptake could be rate-limiting factor for KIC oxidation and thus stimulated insulin release. However, in HIT-T15 cells, the rate of uptake of KIC greatly exceeded the oxidation rate. The low rate of KIC oxidation could explain the poor secretory response of HIT-T15 cells to KIC. PMID- 1643278 TI - Site-specific oligodeoxynucleotide binding to maize Adh1 gene promoter represses Adh1-GUS gene expression in vivo. AB - There is a 36 bp tract of extreme homopurine/homopyrimidine (PuPy) asymmetry in the maize Adh1 gene promoter (from -44 to -79) that is S1-hypersensitive in plasmids under supercoil tension. Oligodeoxynucleotides corresponding to the PuPy tract were designed to examine the secondary structure of the region and address the possible role of the tract in gene regulation. On the basis of oligodeoxynucleotide band-shift and DNase I footprinting analyses, it was concluded that the homopyrimidine oligodeoxynucleotide can form a triple helix with the duplex PuPy tract in vitro. Transient assays in protoplasts, suspension cells, and seedling roots show that the homopyrimidine oligodeoxynucleotide is also capable of repressing Adh1-GUS gene expression during co-transformation, presumably by the formation of a triple helix with the PuPy tract in vivo. The complementary homopurine oligodeoxynucleotide would not form a triple helix in vitro, nor would it repress Adh1-GUS in vivo. We propose that triple helix formation is a potential regulatory phenomenon in vivo, and that an intraregion triple helix could occur within the Adh1 promoter via the formation of H-DNA. PMID- 1643279 TI - Sequence of the fourth and fifth Photosystem II type I chlorophyll a/b-binding protein genes of Arabidopsis thaliana and evidence for the presence of a full complement of the extended CAB gene family. AB - A second locus (Lhb1B) encoding Photosystem II Type I chlorophyll a/b-binding (CAB) polypeptides was identified in Arabidopsis thaliana. This locus carries two genes in an inverted orientation. The predicted sequences of the polypeptides encoded by these two genes show substantial divergence in their amino termini relative to each other and to the proteins encoded by the three Lhb1 CAB genes previously characterized [10], but little divergence within the predicted primary structure of the mature protein. DNA probes derived from seven additional types of tomato CAB genes, encoding chlorophyll a/b-binding polypeptides of several antenna systems of the photosynthetic apparatus, were tested against A. thaliana. Each of these hybridized in Southern blots to unique DNA fragment(s), demonstrating the existence of each of these different types of CAB genes in the genome of A. thaliana. The number of genes encoding each CAB type in A. thaliana was estimated to be similar to that of tomato. PMID- 1643280 TI - Acidic and basic class III chitinase mRNA accumulation in response to TMV infection of tobacco. AB - Complementary DNA clones encoding acidic and basic isoforms of the class III chitinase were isolated from Nicotiana tabacum. The clones share ca. 65% identity, are equally homologous to the class III chitinases from cucumber and Arabidopsis, and are members of small gene families in tobacco. An acidic class III chitinase was purified from the intercellular fluid of tobacco leaves infected with tobacco mosaic virus (TMV). Partial amino acid sequencing of the protein confirmed that it was encoded by one of the cDNA clones. The mRNAs of the class III chitinases are coordinately expressed in response to TMV infection, both in infected and uninfected tissue. The acidic and basic class III chitinases constitute previously undescribed pathogenesis-related proteins in tobacco. PMID- 1643281 TI - Molecular analysis of the plant gene encoding cytosolic phosphoglucose isomerase. AB - The gene encoding a cytosolic isozyme of phosphoglucose isomerase (PGI, EC 5.3.1.9) was isolated from Clarkia lewisii, a wild flower native to California, and the structure and sequence of the entire coding region determined. PGI catalyzes an essential step in glycolysis and carbohydrate biosynthesis in plants. Spanning about 6 kb, the gene has 23 exons and 22 introns, the highest number yet reported in plants. The exons range in size from 43 to 156 nt and encode a protein of 569 amino acids. The protein is about 44-46% identical to the inferred protein sequences of pig, Escherichia coli and Saccharomyces cerevisiae. All of the introns are bordered with the consensus 5'-GT...AG-3' dinucleotides. The longest intron includes a large stem-loop structure bounded by a perfect 9 nt direct repeat. We cloned the PGI gene from a genomic library prepared from a single plant of known PGI genotype. The locus and allele of the clone were identified by matching restriction fragments to fragments from genetically defined genomic DNAs by Southern hybridization. PMID- 1643282 TI - Identification and characterisation of cDNA clones encoding cinnamyl alcohol dehydrogenase from tobacco. AB - Cinnamyl alcohol dehydrogenase (CAD, EC 1.1.1.195) is an enzyme involved in lignin biosynthesis. We have previously isolated pure CAD enzyme as two closely related polypeptides of 44 and 42.5 kDa from tobacco stems. In this paper, we report partial amino acid sequences of these two polypeptides. Based on the peptide sequences mixed oligonucleotides were used to screen a tobacco stem cDNA library and CAD cDNA clones encoding the two polypeptides were identified. DNA sequence comparisons indicate very high sequence identity between these clones both in the coding and in the 5' and 3' untranslated sequences. The close similarity between the two CAD genes leads us to suggest that they do not represent different isoforms but are the same gene from each of the two parental lines of Nicotiana tabacum cv. Samsun. Sequence comparisons with alcohol dehydrogenase 1 (ADH1) from yeast shows sequence similarities of ca. 30%, while comparisons with maize, barley and potato ADH1 sequences show similarities of not more than 23%. PMID- 1643283 TI - The function of vacuolar beta-1,3-glucanase investigated by antisense transformation. Susceptibility of transgenic Nicotiana sylvestris plants to Cercospora nicotianae infection. AB - Vacuolar class I beta-1,3-glucanases (EC 3.2.1.39) are believed to be important in the induced defense reaction of plants to fungal infection. We used antisense transformation to test this hypothesis and to identify other possible physiological functions of this enzyme. Nicotiana sylvestris plants were transformed with antisense constructions containing the region from position 27 to 608 of the coding sequence of the basic, vacuolar beta-1,3-glucanase gene GLA of tobacco regulated by cauliflower mosaic virus 35S RNA expression signals. Plants homozygous for this transgene showed a marked, ca. 20-fold reduction in the constitutive expression of class I beta-1,3-glucanase antigen in their leaves. RNA blot analysis indicated that the antisense plants expressed low levels of the sense transcript of the host beta-1,3-glucanase gene and the antisense transcript of the transgene. Immune blot analysis of plant extracts indicated that only expression of the N. sylvestris homologue of class I tobacco beta-1,3-glucanase and not the acidic, class II isoforms of the enzyme was blocked in the antisense plants. Class I isoforms of beta-1,3-glucanase and chitinase were coordinately induced in leaves of untransformed and empty-vector transformed N. sylvestris plants treated with ethylene or infected with the fungal leaf pathogen Cercospora nicotianae. In antisense plants, chitinase but not beta-1,3-glucanase was induced under these conditions indicating that antisense transformation effectively blocks constitutive as well as induced expression of class I beta-1,3-glucanase. Under greenhouse conditions, antisense plants developed normally and were fertile. The plants did not exhibit increased susceptibility to C. nicotianae infection. These results suggest that expression of the beta-1,3-glucanase isoform blocked by antisense transformation is not necessary for 'housekeeping' functions of N. sylvestris nor defense against the fungal pathogen tested. PMID- 1643284 TI - Regulation of lysine synthesis in transgenic potato plants expressing a bacterial dihydrodipicolinate synthase in their chloroplasts. AB - The essential amino acid lysine is synthesized in higher plants by a complex pathway that is predominantly regulated by feedback inhibition of two enzymes, namely aspartate kinase (AK) and dihydrodipicolinate synthase (DHPS). Although DHPS is thought to play a major role in this regulation, the relative importance of AK is not known. In order to study this regulation, we have expressed in the chloroplasts of transgenic potato plants a DHPS derived from Escherichia coli at a level 50-fold above the endogenous DHPS. The bacterial enzyme is much less sensitive to lysine inhibition than its potato counterpart. DHPS activity in leaves, roots and tubers of the transgenic plants was considerably higher and more resistant to lysine inhibition than in control untransformed plants. Furthermore, this activity was accompanied by a significant increase in level of free lysine in all three tissues. Yet, the extent of lysine overproduction in potato leaves was significantly lower than that previously reported in leaves of transgenic plants expressing the same bacterial enzyme, suggesting that in potato, AK may also play a major regulatory role in lysine biosynthesis. Indeed, the elevated level of free lysine in the transgenic potato plants was shown to inhibit the lysine-sensitive AK activity in vivo. Our results support previous reports showing that DHPS is the major rate-limiting enzyme for lysine synthesis in higher plants, but they suggest that additional plant-specific regulatory factors are also involved. PMID- 1643285 TI - Molecular characterization of tobacco cDNAs encoding two small GTP-binding proteins. AB - We have isolated two cDNAs encoding small GTP-binding proteins from leaf cDNA libraries. These cDNAs encode distinct proteins which show considerable homology to members of the ras superfamily. Np-ypt3, a 1044 bp long Nicotiana plumbaginifolia cDNA, encodes a 24.4 kDa protein which shows 65% amino acid sequence similarity to the Schizosaccharomyces pombe ypt3 protein. The N-ypt3 gene is differentially expressed in mature flowering plants. Expression of this gene is weak in leaves, higher in stems and roots, but highest in petals, stigmas and stamens. Nt-rab5, a 712 bp long Nicotiana tabacum SR1 cDNA, encodes a 21.9 kDa protein which displays 65% amino acid sequence similarity to mammalian rab5 proteins. The expression pattern of the Nt-rab5 gene is very similar to that of the Np-ypt3 gene. The Nt-rab5 gene is virtually not expressed in leaves, higher in stems and roots, and highest in flowers. Both the Nt-rab5 and Np-ypt3 proteins were expressed in Escherichia coli and shown to bind GTP. PMID- 1643286 TI - Functional elements of the Arabidopsis Adh promoter include the G-box. AB - The alcohol dehydrogenase (Adh) gene of Arabidopsis is expressed constitutively in immature seedlings and cells in suspension, and may be induced by hypoxic stress only in roots of mature plants. Deletions and G-box mutations of the Adh promoter were assayed in Arabidopsis protoplasts by PEG-mediated transient expression. Sequence domains necessary for full gene activity are confined to the 384 bp immediately 5' to the transcription start site, and deletion to -177 results in greater than 90% reduction in promoter activity. Site-specific mutations of G-box bases result in greater than 60% reduction in activity and disrupt G-box factor binding in vitro. PMID- 1643287 TI - Isolation and characterization of a cDNA clone encoding the TATA box-binding protein (TFIID) from wheat. AB - We isolated a complementary DNA (cDNA) encoding the TATA-binding factor 'TFIID' from a wheat seedling cDNA library. The wheat TFIID transcript of 1.2 kb poly(A)+ RNA was expressed at a low level early in germination, but gradually increased as the seedlings developed. In vitro binding experiments showed that the bacterially expressed wheat TFIID protein could specifically bind to the TATA boxes of the cauliflower mosaic virus (CaMV) 35S, wheat histone H3 and adenovirus major late genes with different affinity. A comparison with Arabidopsis TFIID showed the presence of a plant-specific region consisting of 13 amino acids at the divergent amino terminus and a conserved region (182 amino acids) at the carboxy terminus longer than that observed in yeasts (180 amino acids) and animals (181 amino acids). PMID- 1643288 TI - cDNA sequence of a sunflower oleosin and transcript tissue specificity. AB - Oleosins (oil body membrane proteins) of 20.5 and 18 kDa have been purified from sunflower (Helianthus annuus) seeds and polyclonal antibodies raised against them. The precipitated rabbit immunoglobulin fraction was purified by affinity chromatography on cyanogen bromide-activated Sepharose and specifically recognised polypeptides of 18 and 20.5 kDa in sunflower homogenate and oil body fractions assayed by western blotting. A near-full-length cDNA clone was isolated for the 20.5 kDa oleosin. The 694 bp cDNA contained an open reading frame of 534 bp, followed by an untranslated region of 81 bp and a poly(A) region of 70 bp. The open reading frame encoded a polypeptide of 19.8 kDa. Study of transcript localisation revealed message to be abundant in the embryo during the later stage of development and still present in the dry seed. No signal was observed in RNA prepared from expanding leaves. PMID- 1643289 TI - Cloning and sequence analysis of the glucose-6-phosphate dehydrogenase gene from the cyanobacterium Synechococcus PCC 7942. AB - The glucose-6-phosphate dehydrogenase (EC 1.1.1.49) gene (zwf) of the cyanobacterium Synechococcus PCC 7942 was cloned on a 2.8 kb Hind III fragment. Sequence analysis revealed an ORF of 1572 nucleotides encoding a polypeptide of 524 amino acids which exhibited 41% identity with the glucose-6-phosphate dehydrogenase of Escherichia coli. PMID- 1643290 TI - Nucleotide sequence of cDNA encoding beta-luffin, another ribosome-inactivating protein from Luffa cylindrica. PMID- 1643291 TI - The evidence for interleukin-6 as an autocrine growth factor in malignancy. AB - Interleukin-6, IL-6, is a pleiotropic cytokine which plays a central role in defense mechanisms, including the immune response, acute phase reaction and hematopoiesis. Abnormal expression of the IL-6 gene has been suggested to be involved in the pathogenesis of a variety of diseases, especially rheumatoid arthritis, Castleman's disease, mesangial proliferative glomerulonephritis, multiple myeloma and Kaposi's sarcoma. In the case of multiple myeloma and Kaposi's sarcoma, the existence of an IL-6-IL-6 receptor autocrine loop has been implicated in the oncogenesis process. On the other hand, IL-6 has a potent anti tumor activity against certain types of tumors. This anti-tumor effect is mediated by in vivo induction of tumor specific cytotoxic T cells and in part by a growth inhibitory activity of IL-6. PMID- 1643292 TI - Tumour necrosis factor: roles in cancer pathophysiology. AB - Tumour necrosis factor (TNF) is a pleiotropic cytokine with activities that extend beyond its antitumour effect. There is now increasing evidence that TNF can be either constitutively produced or induced in human tumours. Tumour cells may also lead to TNF induction in normal cells. Experimental studies implicate TNF in processes that contribute to cancer progression. These range from stimulation of cancer growth and metastasis, to metabolic and haematological disturbances, e.g. cancer cachexia, anaemia, and hypercalcaemia. Future cancer therapies may therefore involve neutralisation of TNF activity in cancer patients. PMID- 1643293 TI - Transfection of interferon-gamma gene in animal tumors--a model for local cytokine production and tumor immunity. AB - After retrovirus-mediated interferon (IFN)-gamma gene transfer, tumor cells constitutively produce IFN-gamma and subsequently increase their surface expression of class I major histocompatibility complex antigens. Such cells are useful for evaluating the comprehensive anti-tumor activity of IFN-gamma in vivo in the mouse. When implanted, the IFN-gamma-producing tumor cells usually lose their tumorigenicity due to specific and/or nonspecific immune responses against the tumor which are probably augmented by the tumor-derived IFN-gamma. This specific immunity is mediated by CD8+ effector cells, i.e. cytotoxic T lymphocytes. Other in vivo effects due to IFN-gamma gene transfer vary with different types of tumor. These results imply a promising potential of tumor-cell targeted IFN-gamma gene therapy against cancer. PMID- 1643294 TI - A comparative serological study of antigenic glycolipids from Mycobacterium tuberculosis. AB - Two fractions of antigenic diacyl trehaloses (DAT1 and DAT2) were isolated from the type strain of Mycobacterium tuberculosis (H37Rv). Phenolic glycolipid (PGL) and polar glycolipid antigens (C1-C4) were isolated from an unusual smooth so called 'Canetti' strain of M. tuberculosis. These lipids were analyzed by enzyme linked immunosorbent assay (ELISA) using antisera against a range of mycobacteria and sera from 50 tuberculosis patients and 25 healthy blood donors. All the lipids gave strong reactions with homologous mycobacterial antisera, except the least polar 'Canetti' polar glycolipid (C4). The phenolic glycolipid (PGL) from the 'Canetti' strain gave only a very weak response with antisera against M. tuberculosis H37Rv. The diacyl trehaloses (DAT) from H37Rv gave only weak reactions with the antisera against the 2 Canetti strains of M. tuberculosis. The 3 most polar glycolipid antigens (C1-C3) from the Canetti strain gave strong responses with serum against M. tuberculosis H37Rv. None of the lipids was able to discriminate between patient and control sera at a level suitable for a serodiagnostic test. A combination of results from several lipids appears to be of greater value in this respect. Thus, PGL, DAT2 and C2 were the best combination, reacting with all but 4 of the patient sera and with only 1 of the control sera. PMID- 1643295 TI - Primary and acquired drug resistance in adult black patients with tuberculosis in South Africa: results of a continuous national drug resistance surveillance programme involvement. AB - Drug resistance is a major problem in the treatment of tuberculosis, and monitoring programmes are essential in control of this disease. The extent of primary resistance in a community is an important indication of the effectiveness of treatment schedules. Since 1965 the Tuberculosis Research Institute (TBRI) of the South African Medical Research Council has performed 25 annual surveys of drug resistance in adult black tuberculosis patients where the disease is most prevalent. Methodology for patient selection, specimen collection, laboratory procedures and criteria for drug resistance were strictly adhered to. All specimens were processed in a central laboratory supervised by the same two technologists. Between 1965 and 1988 a total of 33,111 strains of Mycobacterium tuberculosis were isolated from new cases and 19,134 from old cases. Both primary and acquired resistance to the 5 major antituberculosis drugs has decreased dramatically. Sex and age do not influence resistance rates, while patients' ethnic origin and geographical location do. The results indicate that current tuberculosis treatment practices are satisfactory. The prevalence of primary drug resistance in black South Africans is now intermediate between those countries where eradication of tuberculosis is well advanced and those where the disease remains a public health problem. Also, it can be shown that comparable and clinically significant data can be obtained from a central laboratory employing unsophisticated and inexpensive drug susceptibility testing procedures. PMID- 1643296 TI - High rate of rifampicin resistance of Mycobacterium tuberculosis in the Taif region of Saudi Arabia. AB - This retrospective study was undertaken to determine the prevalence and pattern of resistance to antituberculosis drugs among patients with sputum-proven pulmonary tuberculosis who were seen in Taif Chest Hospital over 24 months (between June 1986 and May 1988). The overall prevalence was 22.6% and the majority (53%) were resistant to two drugs. Resistance to streptomycin was most frequent (16%) followed by rifampicin (15%). Resistance to isoniazid was surprisingly low (6.5%). 23.3% of the resistant group had previously received antituberculosis drugs as against 15.4% in the sensitive group. There was a significant association between previous therapy and resistance to antituberculosis drugs. Recommendations to reduce the problem of resistance and to improve compliance are discussed. PMID- 1643297 TI - Activity of two long-acting rifamycins, rifapentine and FCE 22807, in experimental murine tuberculosis. AB - The efficacy of the long-acting rifamycins, rifapentine (RPE) and FCE 22807 (FCE) in experimental murine tuberculosis was studied by counting viable bacilli in spleens. At 2 weeks after infection with Mycobacterium tuberculosis, strain H37Rv, treatment with isoniazid 25 mg/kg, rifampicin 10 mg/kg and pyrazinamide 150 mg/kg was given daily for 6 weeks. The mice were then divided into groups given RPE or FCE at intervals of 1, 2 or 3 weeks with spleen counts after 18 and 24 weeks of chemotherapy. The first experiment showed the great effect of the size of the dose of RPE, which, in once-weekly regimens, caused rapid sterilization at 16 mg/kg, less rapid sterilization at 10 mg/kg and incomplete activity at 6.25 mg/kg. Regimens of RPE given every 2 or 3 weeks were less effective, though 16 mg/kg fortnightly was as good as 6 mg/kg once-weekly. The second experiment compared RPE and FCE each given at 12 or 8 mg/kg. The results were similar though, at 8 mg/kg every 2 or 3 weeks, FCE was slightly more effective than RPE. Serum assays showed that the levels with 8 and 12 mg/kg FCE were lower than those produced even by 6.25 mg/kg RPE, suggesting that FCE would be a better drug than RPE if its bioavailability could be improved, and that the levels following 16 mg/kg RPE were similar to those found in man after 8 mg/kg RPE taken with a fat-rich meal, suggesting good prospects for effective once fortnightly human treatment. The potential for long-acting rifamycins in the management of pulmonary tuberculosis is discussed. PMID- 1643298 TI - Pustular vasculitis complicating BCG vaccination. PMID- 1643299 TI - Tuberculosis forgotten? PMID- 1643300 TI - Microepidemics of tuberculosis: the stone-in-the-pond principle. AB - In a low prevalence country with no systematic BCG vaccination and a low frequency of environmental mycobacterial infections, for each recognized case of tuberculosis or infection with M. tuberculosis source detection should be undertaken. Sometimes this search will lead to discovery of a microepidemic. The extent of contact screening in a microepidemic can easily be determined if observed group prevalences are compared to expected group prevalences. The described method illustrates this search for contacts in concentric circles around the source case: the stone-in-the-pond principle. PMID- 1643301 TI - Deaths in tuberculosis patients in British Columbia, 1980-1984. AB - Records of all 1884 newly notified tuberculosis cases, over the 5-year period 1980-1984 in British Columbia, Canada, were reviewed and 201 deaths were identified, including 48 diagnosed only after death, and 153 who died while on treatment; 56 of unrelated causes, 67 in whom tuberculosis was a contributing cause, and 30 in whom it was the principal cause. Significant predictors of death while on treatment (specific to tuberculosis) were the extent of disease, history of previous disease and sputum smear-positive for acid-fast organisms. Significant predictors of failure of diagnosis, in patients who died, were the presence of disseminated disease and the absence of a history of previous disease. The presenting features were not different in those dying, in whom the diagnosis was made before, as compared with after, death. The most frequent mode of death due to tuberculosis was respiratory failure, followed by multiple organ system failure and haemoptysis. The case fatality rate was low (1.6%) and did not change over 10 years. One-half of patients whose death was due to tuberculosis were diagnosed only after death and this had not changed over 10 years. We conclude that death due to tuberculosis is uncommon in patients while on treatment and that the main reason for death due to tuberculosis is that some patients are not diagnosed, and therefore not treated, before they die of the disease. PMID- 1643302 TI - Rising case fatality of bacteriologically proven pulmonary tuberculosis in The Netherlands. AB - Analysis of registration cards from the Tuberculosis Control Program (TCP) showed a four-fold increase in case fatality of bacteriologically proven pulmonary tuberculosis in Dutch patients in the period 1973-1984. Registered data of 125 deceased patients whose primary cause of death was pulmonary tuberculosis were analyzed. Increased case fatality predominantly occurred in the elderly. Elderly patients presented often with other, less specific, complaints than coughing, but had a shorter combined patient's and doctor's delay than younger patients. The elderly were more often treated with 3 tuberculostatic drugs (INH, pyrazinamide, rifampin). Bacterial resistance was found in only 2%. Probably the most important factor concerning the raised case fatality in the elderly is the decline in immune response, due to ageing of the Dutch population. An effective response to tuberculostatic drugs needs a reasonably intact immune response. Declining immunity of the elderly group will increase incidence and mortality of pulmonary tuberculosis in this group. PMID- 1643303 TI - Sensitivity to PPD tuberculin and M. scrofulaceum sensitin in schoolchildren BCG vaccinated at birth. AB - OBJECTIVE: To determine the degree of and variation in sensitivity to PPD RT 23 tuberculin and M. scrofulaceum sensitin RS 95 at school age in children BCG vaccinated at birth. DESIGN: Double-testing by applying standard WHO Mantoux tests and inspecting BCG scars. SETTING AND PARTICIPANTS: Urban and rural schools in Southwest Finland, 1091 children aged 11-13 years. MAIN OUTCOME MEASURES: Size of tuberculin and sensitin indurations and BCG scar (mm). RESULTS: The mean size of tuberculin indurations was 7.2 mm, sensitin indurations 8.1 mm and BCG scars 7.9 mm. The reaction to sensitin was significantly larger than to tuberculin (95% confidence interval 0.58-1.10 mm) and the zero reactions to sensitin were fewer. Correlation between tuberculin and sensitin indurations was significant (r = 0.75, 95% confidence interval 0.72-0.77). There were induration greater than or equal to 15 mm to tuberculin in 16% and to sensitin in 14%. Sensitin indurations exceeded those of tuberculin by 4 mm or more in 14% of the children with at least 5 mm tuberculin indurations. CONCLUSIONS: High tuberculin sensitivity in healthy schoolchildren may be partially maintained by contact with environmental mycobacteria. Our data do not prove but very probably indicate that children have protective immunity. In view of the current incidence of tuberculosis in Finland and the likelihood that lymph node infections and sensitivity to environmental mycobacteria will increase, continued BCG vaccination at birth is recommended. PMID- 1643304 TI - Determinants of tuberculin sensitivity in a child population covered by mass BCG vaccination. AB - A cross-sectional survey of 701 Indian children aged 1-15 in five northern Canadian communities showed that 82% had a documented history of BCG vaccination while only 78% had a visible scar. The prevalence of 5 mm or more induration on Mantoux testing varied from 6 to 26%. Multiple logistic regression indicated that community, age, past use of isoniazid and time since the last Mantoux test were positive predictors of sensitivity. The presence of a BCG scar and the number of past vaccinations were not significantly associated but the elapsed time since the last BCG was negatively associated with a positive reaction. Overcrowding, nutritional status and past history of household and community contact with an active case of tuberculosis were also investigated but their independent effect could not be demonstrated. Despite the presence of mass BCG vaccination in this population, tuberculin testing is still a useful tool in assessing the risk of infection. PMID- 1643305 TI - The same genomic region is disrupted in two transgene-induced limb deformity alleles. AB - Mutations of the mouse limb deformity locus, ld, map to Chromosome (Chr) 2 and result in defects in the morphogenesis and patterning of the limb and kidney. Complementation studies have defined the existence of five recessive ld alleles. Remarkably, two of these, ldTgHd and ldTgBri, are transgene-induced mutations. Recovery of the first transgene insertional allele, ldTgHd, facilitated the molecular cloning of a large (greater than 200 kb) candidate gene at the ld locus. This gene is broadly transcribed and encodes a set of novel protein isoforms, termed formins. Here we present characterization of the ldTgBri mutation that supports the molecular identification of the ld gene. We show that the ldTgBri fails to complement both the ldTgHd and the ldOR alleles and that it has undergone a genomic deletion that disrupts the cloned ld gene and its transcripts. Curiously, the ldTgBri deletion encompasses the same 11-kb interval in which the ldTgHd insertion occurred and in which a chromosomal rearrangement has been identified in a third allele, ldIn2. These findings suggest that this region of the ld gene is a preferential site for illegitimate recombination. PMID- 1643306 TI - Intracisternal A-particle-specific oligonucleotides provide multilocus probes for genetic linkage studies in the mouse. AB - Oligonucleotide probes representing distinct intracisternal A-particle (IAP) subfamilies were derived from the long terminal repeats (LTRs) of transcriptionally active IAP genes in normal mouse cells. These probes were used to examine the distribution of IAP proviral elements in the genomic DNA of several inbred mouse strains. Each oligonucleotide probe identified multiple polymorphisms between the different strains. The distribution of polymorphic restriction fragments among the CXB set of recombinant inbred (RI) strains demonstrates the feasibility of using these probes for chromosome mapping. These and other subset-specific IAP probes can provide a useful series of multilocus markers for genomic mapping and genetic analysis in the mouse. PMID- 1643307 TI - Estimation of microsatellite mutation rates in recombinant inbred strains of mouse. PMID- 1643308 TI - Linkage analysis of 84 microsatellite markers in intra- and interspecific backcrosses. PMID- 1643310 TI - The mouse homolog to the ras-related yeast gene YPT1 maps on chromosome 11 close to the wobbler (wr) locus. PMID- 1643309 TI - Localization of the interleukin-3 gene to rat chromosome 10 by linkage analyses with a variable number of tandem repeats (VNTR). PMID- 1643311 TI - Map positions of four dinucleotide repeats in the mouse t complex. PMID- 1643312 TI - Respiratory medicine. PMID- 1643313 TI - Diagnostic pulmonary imaging. AB - This article examines four common but often confusing radiologic problems: the normal thoracic radiograph (performed when clinical suspicion of pulmonary disease is high), the solitary thoracic mass, loss of organ margination, and the mixed pulmonary pattern. Through the use of case examples, a systematic approach to each of the four problems is taken. Contrast and positional radiography, scintigraphy, ultrasonography, and computed tomography are discussed to demonstrate their applications in pulmonary imaging. A brief review of image formation and interpretation of alternate techniques will be provided. The discussion identifies some of the limitations of the radiographic examination, shows why they exist, and illustrates ways of overcoming them. PMID- 1643314 TI - State-related changes in breathing. Are we missing sleep-disordered breathing syndromes in veterinary patients? AB - In recent decades, treatment of sleep disorders has developed rapidly. Prevalent and severe sleep disorders affecting respiration have been discovered in clinical sleep disorders centers. Although sleep studies are not currently, and may never become, a clinical tool for veterinarians, evidence from investigative work shows that dogs, at least, can suffer from "sleep-disordered breathing" syndromes similar to those affecting humans. The physiology and pathophysiology of sleep and breathing are strikingly similar in dogs and humans. PMID- 1643315 TI - Lung infections and infestations. Therapeutic considerations. AB - This article discusses two common causes of lung disease in the dog and cat: tracheobronchitis and bacterial pneumonia. Information about parasitic infestation of the trachea, bronchi, and lung parenchyma is summarized. Data are also presented regarding the sensitivities of bacterial infections of the respiratory tract to antibiotics. PMID- 1643316 TI - Primary ciliary dyskinesia in the dog. AB - A disorder caused by congenital ciliary dysfunction occurs in dogs. Most of the clinical signs are directly or indirectly attributable to immotile or dyskinetic cilia and spermflagella. Due to severely impaired mucociliary clearance, a continuous mucoid nasal discharge and intermittent sneezing and coughing are typically observed during the neonatal period. Recurrent bacterial rhinosinusitis and bronchopneumonia usually start within a few weeks of birth. Hypoplastic nasal sinuses and atresia of the frontal sinuses are variable features of the disease that may be caused by neonatal colonization of these structures by specific bacteria. Bronchiectasis is an acquired lesion resulting from chronic inflammation and obstruction of airways. A secretory otitis media is caused by dysfunction of the cilia in the middle ear, and is manifested in some dogs by sclerotic tympanic bullae. Male infertility is caused by live, but immotile to hypomotile spermatozoa; however, unexplained oligospermia and azoospermia have been reported. Hydrocephalus and situs inversus are common but variable features of the disease; the genesis of these lesions has not yet been determined. The probable mode of inheritance is autosomal recessive, but dominant mutations cannot be excluded. The diagnosis can be confirmed by demonstrating the absence or near absence of nasal or tracheal mucociliary clearance and the presence of a specific ultrastructural lesion in a large percentage of cilia from multiple sites (airways, middle ear, or oviduct). The ultrastructure of sperm flagella should mirror that of the cilia. Not all dogs have ultrastructural ciliary lesions, and in these cases, results of in vitro analysis of ciliary activity may be highly suggestive, if not diagnostic. In dogs without mucociliary clearance in which structural and functional analysis of cilia are not diagnostic, confirmation of congenital ciliary dysfunction can be established only by ruling out other diseases with similar signs (e.g., congenital immunodeficiency syndromes). The clinical course in an longevity of affected dogs are highly variable. Appropriate antibiotic treatment and pulmonary physical therapy may result in prolonged survival, although cor pulmonale and reactive systemic amyloidosis are potential sequelae of chronic hypoxia and chronic bacterial infection of the airways, respectively. PMID- 1643317 TI - Chronic lower airway disease in the dog and cat. AB - The most common form of lower airway disease (LAD) in dogs is chronic bronchitis, whereas in cats a syndrome resembling chronic bronchial asthma in humans is commonly reported. In most cases, the cause(s) of LAD remains unproven. The primary symptom of LAD in dogs and cats is chronic cough, although many cats are free of symptoms between episodes of acute, life-threatening bronchoconstriction. Diagnosis is based on a careful history, physical examination, and diagnostic tests designed to rule out other causes of cough and dyspnea such as pneumonia, heartworm infestation, and congestive heart failure. More sophisticated tests, such as bronchoscopy, flow volume loops, and radioisotope ventilation scans are available to define the extent of the disease process better. Glucocorticoids remain the mainstay of chronic therapy for most dogs and cats with LAD. Bronchodilators are indicated for most cats with symptoms of acute bronchoconstriction, whereas a smaller number of dogs may respond to bronchodilator administration and demonstrate an increase in exercise capacity and a decrease in cough frequency. LAD in dogs and cats is a progressive disorder, and prognosis is guarded. Nevertheless, with aggressive medical management many of these animals can live relatively symptom-free lives. PMID- 1643318 TI - Respiratory complications of endocrine disorders. AB - This article provides an overview of the respiratory manifestations of endocrine disorders. The patient with endocrine disease may present with various clinical signs referable to the respiratory system. Furthermore, such respiratory problems may complicate patient management. Therefore, it is important for the clinician to be cognizant of alterations in pulmonary function associated with disorders of the endocrine system. PMID- 1643319 TI - Chemotherapy for intrathoracic cancer in dogs and cats. AB - The thoracic cavity contains numerous tissue types from which tumors may arise. Broadly speaking, the cavity is comprised of the pleural surfaces, the mediastinum and its enclosed viscera, and the lungs. Neoplasms arising from these structures are frequently advanced at the time of diagnosis, and surgery is rarely curative for malignant processes. Although reports describing anticancer chemotherapy use in dogs and cats for tumors of the thoracic cavity largely have been anecdotal, as advances are made in the chemotherapeutic management of comparable tumors in human cancer patients and as veterinarians become familiar with these compounds, use of antineoplastics as an adjunct to, or in place of, local treatment modalities should increase. This article reviews the epidemiology, clinical features, and diagnosis of pulmonary neoplasia; mediastinal neoplasia, particularly thymoma; and pleural neoplasia, with emphasis on mesothelioma. In addition, options for chemotherapy, derived from both the human and veterinary literature, are given for each tumor type. PMID- 1643320 TI - Respiratory complications in the critically ill animal. AB - Respiratory dysfunction in a critically ill animal is a life-threatening complication that often presents a challenge to patient management. In the critical care setting, the most severe respiratory complications include nosocomial pneumonia, pulmonary thromboembolism (PTE), and acute respiratory distress syndrome (ARDS). Successful treatment of acute respiratory failure, although difficult, can be enhanced by recognition of predisposing factors, knowledge of underlying pathophysiologic mechanisms, and early prophylactic and therapeutic intervention. PMID- 1643321 TI - Alternative treatment of heartworm disease. AB - Conventional adulticidal therapy may cause acute death due to embolism in major pulmonary arteries resulting in severe infarction of the lung. To avoid this problem removing a significant number of worms with flexible alligator forceps prior to adulticidal therapy is recommended. Before surgery, an accurate diagnosis and critical evaluation of the patient is mandated for proper choice and sequence of treatment. PMID- 1643322 TI - Medical management considerations for upper airway disease. AB - The conducting airways, also commonly referred to as the upper airways, provide for the passage of air to and from the atmosphere and lungs. Anatomical components include the nasal passages, pharynx, larynx, trachea, and mainstem bronchi. Clinical problems involving the conducting airways can be manifested by relatively mild clinical signs of stertorous breathing, by life-threatening dyspnea, or by chronic bouts of inspiratory stridor and cough. Concurrent disease of the lower respiratory system (ie, chronic bronchitis) as well as other organ systems (ie, cardiovascular, nervous, endocrine) may significantly contribute to the etiology and pathophysiology of upper airway disease. Diagnosis of the diseases of the conducting airways is primarily based on history and physical examination. The dynamic nature of some conditions, related to the phases of respiration, can make diagnosis more difficult. In addition to direct visualization, radiographic and endoscopic evaluation are often useful. Many upper airway problems, especially congenital conditions, lend themselves to surgical palliation that should be performed as early in life as possible. Medical management is often directed at treating underlying diseases and the relief of clinical signs. Historically, the use of variety of drugs have been advocated and frequently include decongestants, cough suppressants, bronchodilators, glucocorticoids, and antibiotics. However, their use may be detrimental and contraindicated. In addition, therapy for some conditions (ie, laryngeal paralysis and intrathoracic tracheal collapse) may be better directed at increasing airway muscle tone in order to stabilized airway patency. Therapeutic agents that may be useful include aspirin and digitalis. The overall objective to medical management must be to balance potential therapeutic benefit against untoward effects in order to minimize clinical signs and to improve the animal's quality of life. PMID- 1643323 TI - [Public health and citizen involvement--guidelines and general practice in Herne]. AB - Health problems cannot be solved only by expanding medical and other systems of service. Limitations of these services are not only set by costs, but also by the disease patterns themselves. The traditional role of the patient must be redefined. It is necessary to develop personal health-coping strategies outside medical care, and for the citizen to participate in improving conditions of health in general. The public health system has the specific duty of initiating and establishing these new approaches to health promotion and coping with disease. A model for these new municipal health policies is presented with reference to medical practice in the city of Herne in the Ruhr area of Germany. PMID- 1643324 TI - [Ecology--health--medicine--ecologic health strategy]. AB - Ecological problems call for a revolution in medical thinking. The basic ideas of research methodology and social application of traditional forms of medicine in society are beginning to falter, have to be examined, replaced, elaborated or made more precise. The article analysis the methodological barriere of medical/ecological research and the necessity for ethics of prevention. A basic introduction is presented with regard to the metabolic concept of the interaction between Man and Nature and the creation of a social environment from a theoretical scientific and ethical perspective. The concept of medicine as a natural Science is criticised. PMID- 1643325 TI - [Procedures of the public health office during an outbreak of infectious enteritis in community institutions]. AB - On the occasion of a local epidemic of infectious enteritis in a Community centre, the Public Health Office had an opportunity to develop a procedure to deal with such outbreaks. Models for the tasks of Public Health Offices are suggested. These consist of investigation, control measures, documentation of the epidemic and assessment of the chosen procedures. Typical problems include pressure of time due to the large number of cases, the dilemma between the need to inform the population vs. professional secrecy, and the dual role of the Public Health Office in providing assistance in both medical consultation and epidemic control measures. PMID- 1643326 TI - [Claims and reality of public health expert assessment using legal public health guidelines]. AB - The following article deals with the discrepancy between legal pretension and the practice of medical expertise in examinations for engagement, fitness for service or courses of medical treatment. To avoid injustice to the patients and conflicts for the experts, clear-cut general directions for the practice of medical expertise are demanded. PMID- 1643327 TI - [Waste prevention and recovery of valuable raw materials in the hospital]. AB - Quite a number of the diseases with which Public Health services are concerned are due to environmental factors. It is our aim that especially the Public Health staff should tackle with efficiency and dispatch all the problems connected with damage caused by such factors. Environmental protection is in fact Medical Science. The volume of the waste deposits has been exhausted to the full. Burning of refuse is not the proper alternative: natural science tells us that it is definitely no solution of the problem. The best kind of waste is not to waste anything, i.e. waste that does not arise at all. The belief that disposable or throwaway goods improve hygiene, is totally erroneous and a misconception. All persons engaged in Public Health must unanimously demand from industry the production of high-quality, well sterilisable and easy-to-clean package items for repeated use. Active environmental protection motivates the staff and enhances the reputation of their work. PMID- 1643328 TI - [Effects of prednisolone on energy metabolism in patients with pulmonary tuberculosis and pneumonia]. PMID- 1643329 TI - [Prognostic significance of cytochemical tests in peptic ulcer]. AB - The paper is concerned with evaluation of the activity of the intracellular enzymes of lymphocytes--succinate dehydrogenase and alpha-glycerophosphate dehydrogenase of mitochondria, in patients with peptic ulcer running a different course to define their importance in the disease prediction. Aggravation of peptic ulcer was found to result at first in marked activation of lymphocyte energy supply including that at the expense of the formation of new cellular populations. Later the count of lymphocytes with a high enzymatic activity was found to decline together with a reduction of enzymatic activity. The retention of the indicated changes after ulcer healing serves a prognostically unfavourable sign of the further disease course. PMID- 1643330 TI - [Results of clinical care of children in contact with HIV-infected persons]. PMID- 1643331 TI - [Somatogenic toxic-circulatory encephalopathies with pseudotumorous course]. AB - A progredient course of cerebral circulatory disorders in grave-condition somatic patients may present a clinical picture of toxic dyscirculatory encephalopathy with brain symptoms of mass lesions. Pseudotumorous run of a chronic vascular process requires a sound clinical analysis and adjuvant methods of examination to rule out primary tumor or brain metastases. PMID- 1643332 TI - [Yersiniosis]. PMID- 1643333 TI - [Current methods of treatment of infection]. PMID- 1643334 TI - [Segmental vegetative disorders]. PMID- 1643335 TI - [Early repolarization syndrome as a marker of additional conduction pathways in ischemic heart disease]. PMID- 1643336 TI - [Treatment of congestive heart failure with sodium nitroprusside infusions in association of chronic obstructive lung diseases and postinfarct cardiosclerosis]. PMID- 1643337 TI - [A differential approach to cavinton and finoptin treatment of patients with circulatory encephalopathies]. PMID- 1643338 TI - [Short-term results of the treatment of patients with breast cancer using various laser units as a laser scalpel]. PMID- 1643339 TI - [Surgical treatment of renal artery occlusion]. PMID- 1643341 TI - [Associated chronic diseases in workers of poultry farms]. PMID- 1643340 TI - [Radiotherapy of prostatic cancer and its administration in the prehospital period of patient management]. PMID- 1643342 TI - [Study of factors influencing the time of detection of gastric cancer]. PMID- 1643343 TI - [A case of Buschke-Lowenstein condyloma of the face in immunodeficiency state and effects of cryosurgery]. PMID- 1643344 TI - [Pseudotumorous brain stem encephalitis of herpetic etiology in adults]. PMID- 1643345 TI - [Ventricular ejection fraction in oxygen therapy of patients with pulmonary tuberculosis]. AB - Radionuclide study of ejection fraction of the right heart ventricle was carried out in lung tuberculosis patients with respiratory insufficiency and cor pulmonale. Oxygen therapy was found to promote reduction of right ventricle heart failure in effective treatment of lung tuberculosis. The greatest reduction of heart failure was recorded in cases where oxygen therapy was combined with cardiac glycosides. As the tuberculosis process progresses, oxygen therapy does not decrease right ventricle heart failure. The treatment by antibacterial agents alone without using oxygen does not lead to the rise of ejection fraction of the right ventricle of the heart. PMID- 1643346 TI - [Occurrence of rectal polyps in patients with uterine myoma]. PMID- 1643347 TI - [Diabetes mellitus and cancer]. AB - There is evidence on infrequent cases of combined occurrence of cancer and diabetes mellitus (DM). The latter is likely to inhibit malignant growth (W. Rhomberg, G. Jorns, M. A. Kunitsina) as shown by reduced number of metastases and recurrences, especially in noninsulin-dependent DM, longer survival. Presence of cancer, in its turn, diminishes DM manifestations. Radical removal of the tumor promoted rapid DM decompensation. Cancer prognosis in DM presence is dependent on the anatomo-morphological pattern of the lesion and DM type. PMID- 1643348 TI - [Several indicators of hormonal homeostasis (hypophysis--gonads) in patients with hypertension]. AB - One hundred and sixty-three male patients with essential hypertension (EH) stage I (68 subjects) and II (95 subjects) were compared to healthy controls by concentrations of renin, aldosterone, LH, FSH, prolactin and estradiol assessed by means of radioimmunoassay. The findings show that unlike healthy controls EH patients have low levels of LH and testosterone, high prolactin and unchanged FSH and estradiol concentrations. The involutional dynamics is similar for patients and controls: dissociation in the levels of hypophyseal hormones and testosterone. An age-specific trend in prolactinemia was related to EH severity. PMID- 1643349 TI - [Diagnosis of trophologic insufficiency]. AB - Nutrition is a very important factor in maintenance of human health. Defects in nutrition may become the main "killer" and "pathogen" in current human society. Malnutrition can modify host defenses, influence the disease patterns and outcomes. The paper introduces the notion "trophologic status" as an indicator of human health. The definition is presented. Assessment of the trophologic status can be conducted by various methods useful for different medical institutions in early diagnosis of trophologic insufficiency in patients. PMID- 1643350 TI - [Detection of the pathology of the major cerebral arteries in transient disorders of cerebrovascular circulation using Doppler ultrasonography]. AB - One hundred and six males aged 40-59 were examined generally, neurologically and using ultrasonic dopplerography within one month following an emergency call for transitory ischemic attacks, hypertensive cerebral crises. Ultrasound signs of arterial lesions were recorded in 79.2% of the examinees. Hemodynamic disturbances occurred most frequently (50.9%). Arterial stenosis was diagnosed in 27.4% of cases. With growing number of risk factors, the incidence of major arteries lesions was on the increase. PMID- 1643351 TI - [Results of x-ray studies on the development of giant cell tumors in the tubular bones]. AB - Giant cell tumor definition is still a debatable problem in medicine. The disease is referred to as giant cell tumor, osteoblastoclastoma, local fibrous osteodystrophy. X-ray follow-up of more than twenty patients gave the author arguments in favour of the disease belonging to fibrous osteodystrophy. Roentgenologically, it is characterized by two phases: destructive with typical structureless defects and restorative with typical cellular structures of the affected bone site. For the most part, the disease is benign, rare cases of malignant transformation are attributed to adverse factors. PMID- 1643352 TI - [Chronic disseminated lung diseases: diagnostic and therapeutic tactics]. PMID- 1643353 TI - [Computerized tomography in emergency states]. PMID- 1643354 TI - [Rare neoformations of the adrenal glands]. PMID- 1643355 TI - [Characteristics of autoimmune process in melanoma of the uveal tract]. PMID- 1643356 TI - [Ultrasonic diagnosis in the 1st trimester of pregnancy]. PMID- 1643357 TI - [Effects of laser therapy on microstructure of the blood serum of patients with ischemic heart disease]. PMID- 1643358 TI - [Effectiveness of the use of zaditen and leakadin in recurrent erysipelas]. PMID- 1643359 TI - [Prevention of postoperative thrombotic complications by a combination of small doses of heparin and digitamin in oncologic patients]. PMID- 1643360 TI - [Oxyprogesterone capronate in the treatment of menstrual epilepsy]. PMID- 1643361 TI - [Effects of caloric value of parenteral nutrition on the effectiveness of cytostatics and ribonucleases in the treatment of patients with acute pancreatitis]. PMID- 1643362 TI - [Treatment with calcium antagonist nifedipine in pathology of the preliminary period]. PMID- 1643363 TI - [Use of anabolic steroid retabolil in patients with inflammatory diseases of the uterus and its appendages]. PMID- 1643364 TI - [Scope of surgery in severe craniocerebral trauma]. PMID- 1643366 TI - [Medicine of disasters and their differentiation according to severity]. PMID- 1643365 TI - [Koshevnikoff's epilepsy in a child]. PMID- 1643367 TI - [Possibilities of the use of health status indicators as criteria of adaptation to expedition-duty work]. PMID- 1643368 TI - [Remission of Itsenko-Cushing disease after treatment with nizoral]. PMID- 1643369 TI - [Clinico-morphological characteristics of hemochromatosis]. PMID- 1643370 TI - Nurses' role in relation to substance misuse. PMID- 1643371 TI - Discontent among enrolled nurses. PMID- 1643372 TI - Preoperative nursing intervention to relieve stress. AB - Stress and anxiety produce physiological and psychological distress which impedes recovery postoperatively. Nurses can facilitate patient independence preoperatively through a combination of sensory stimulation techniques, communication and counselling. PMID- 1643374 TI - Use of music in therapeutic care. AB - Nursing is currently examining issues that relate to quality of care. One way in which nurses can provide higher standards is by improving the environment and patient care with the use of piped, background music. PMID- 1643373 TI - Partnership in care: paediatric nursing model. AB - In 1988, Casey developed her partnership in care model for use within the paediatric healthcare setting as she felt that other models did not recognize or emphasize concepts that she deemed essential for effective paediatric care. This has now been adopted by the Hospitals for Sick Children as the model of care. PMID- 1643375 TI - Implementing problem-solving approaches in clinical practice. AB - When analysing any nursing problem or situation, different approaches are always possible. A knowledge of the possible angles of approach can make nurses into more flexible problem-solvers. This article explores the holistic and reductionist approaches to patient care. PMID- 1643376 TI - Hyperosmolar non-ketotic hyperglycaemia. AB - Thorough assessment of the patient and good understanding of potential complications enhance patient care and safety. Correction of volume depletion and maintenance of a strict fluid balance chart is essential to avoid complications of congestive cardiac failure, cerebral or pulmonary oedema, renal failure and further dehydration. Careful monitoring of electrolytes and administration of supplements should be undertaken to prevent instability. Regular monitoring of blood glucose levels and careful insulin administration should be undertaken to prevent fluctuations in blood glucose levels. Any possible source of infection should be identified and treated as prescribed. Good basic nursing care for the patient and support and counselling for the patient and his family are essential components of holistic care. PMID- 1643378 TI - Nurses have rights too. PMID- 1643377 TI - Advances in clinical practice. PMID- 1643379 TI - HIV/AIDS: the ethical and legal dilemmas. AB - Regardless of personal feelings and fears, all healthcare practitioners have a duty to uphold the rights of HIV/AIDS patients. Dilemmas arise when the practitioner's responsibilities are split between upholding these rights and enforcing those of other at-risk individuals. PMID- 1643380 TI - Preparing for an interview. AB - Selection interviews provoke fear in many confident nurses and are among the most stressful situations nurses experience. Thorough preparation can assist you in achieving a positive outcome. This article considers the preparatory stages and recommends how you should conduct yourself to achieve success. PMID- 1643381 TI - The process of change in nursing audit. AB - This article reviews the current literature on change in nursing audit in order to develop a strategy for nursing staff. It suggests that the model for change will affect the nature of the measurement phase of audit, and proposes that an open systems model be adopted and a change agent incorporated to manage the audit cycle. PMID- 1643382 TI - Healthcare in Finland. AB - Finland has nearly the highest suicide rate and mortality from cardiovascular disease in the world. Healthcare needs are varied and create challenges for nursing practice. PMID- 1643383 TI - Chiral separation by high performance liquid chromatography. I. Review on indirect separation of enantiomers as diastereomeric derivatives using ultraviolet, fluorescence and electrochemical detection. AB - The increased attention on the therapeutic implications of stereoisomerism has provided an impetus for the development of analytical methods for enantiomeric separation. The indirect method of separation of enantiomers as diastereomers using high performance liquid chromatography (HPLC) has emerged as an efficient and versatile approach. This is due mainly to the availability of numerous chiral derivatization reagents (CDRs). This article reviews CDRs useful for the development of an indirect HPLC method using ultraviolet, fluorescence and electrochemical detection. In addition, factors crucial for the development of the indirect method are discussed. PMID- 1643384 TI - Determination of intraperitoneal mitoxantrone in the serum of cancer patients using a high performance liquid chromatograph coupled to an Advanced Automated Sample Processor (AASP). AB - A study has been carried out on 10 patients with ovarian cancer treated by intraperitoneal mitoxantrone. The serum concentration was determined by high performance liquid chromatography with spectrophotometric detection. The extracted analyte on the cartridge was injected and eluted on-line into the analytical column by the mobile phase. This improved the signal and sample processing rate, without significant loss in analytical performance. Excellent linearity (r greater than 0.9994) was observed for the calibration curve over the range 1-2000 ng/mL, along with a precision within-day and between-day estimated as 1.5% and 5.6%, respectively. Sensitivity was an order of magnitude higher than that of the comparison method. From a clinical point of view, these preliminary results have shown that intraperitoneal administration is more beneficial than intravenous therapy. Low serum levels (1-30 ng/mL) with a maximum at the first or second hour are revealed. PMID- 1643385 TI - Multimodal liquid chromatographic separation methods in the study of ethimizol metabolism in man. AB - The metabolism of ethimizol in the human body has been investigated. Focus was on the detection and demonstration of the regioselective pathway of metabolic demethylation of ethimizol by determining the presence of the corresponding metabolites in blood, saliva and urine. Isolation, purification and identification of the metabolites present in the biological samples was achieved by applying a combination of the following methods: solid phase extraction, high performance liquid chromatography, high performance thin layer chromatography, nuclear magnetic resonance and mass spectrometry. The suggested chemical structures were definitely established by comparing the physicochemical characteristics of the ethimizol metabolites obtained from the individual biological fluids with the characteristics of synthetized authentic derivatives. PMID- 1643386 TI - Non-labelled benzodiazepines partitioned into synaptosomal membranes: their extraction and quantification by high performance liquid chromatography. AB - A method for the extraction and quantification by high performance liquid chromatography (HPLC) of non-labelled benzodiazepines partitioned into biological membranes has been developed. The benzodiazepine (BZD) was partitioned in a synaptosomal membrane-buffer system. The membranous pellet was separated by centrifugation and from this pellet, previously submitted or not to a proteolytic treatment and resuspended in the same buffer, the BZD was extracted by the addition of the proper volume of ethyl acetate, i.e. that capable of extracting at least 99.5% of the total drug in the aqueous phase. Optimal conditions for maximum proteolysis were: incubation of membranes at a final concentration of 1 mg protein/mL in the presence of 0.08 mg of Protease type I per mL for 90 min. at 45 degrees C. Although the efficiency of the proteolysis was demonstrated not only by kinetic but also by electrophoretic evidence, recovery of BZD in the organic solvent was not increased by the enzymatic treatment at a mass BZD/protein ratio in the range 4-4.6 10(-5) micrograms BZD/mg protein. For the HPLC quantification a reversed phase ODS column was used with methanol:water (1:1) plus 3.5% acetic acid as the mobile phase at a constant pressure and 1 mL/min flow rate. The UV detector was calibrated at 265 nm. Calibration curves were constructed by plotting peak height or peak area vs. nmoles BZD and adjusted to straight lines by a regression analysis by the least squares method. The peak height was selected as the detection method. Intra- and inter-assay precision did not exceed 10% and the total recovery was 100%. PMID- 1643387 TI - Simultaneous determination of pseudouridine and creatinine in urine of normal children and patients with leukaemia by high performance liquid chromatography. AB - A reversed phase high performance liquid chromatographic method for the simultaneous determination of pseudouridine (PU) and creatinine (Cr) in urine is described. The mobile phase was 0.01 mol phosphate buffer (pH 6.1) containing 2.5 mmol octanesulphonic acid as the ion pairing agent. UV detection was set at 250 nm. Variation in pH value affected the retention time of PU and Cr significantly; Their separation from interfering peaks was also affected. The recoveries of PU and Cr were 89.93% and 90.35%, respectively. The standard deviation of the method for PU was 48.69 +/- 0.063 (nmol/mumol Cr, mean +/- SD, n = 5). The urine samples from 233 normal children of different ages and 119 patients with leukaemia were analysed by this method. The normal reference value was appraised by comparison with the percentage of immature cells in the bone marrow. The results showed that the sensitivity of the method was 94.12%, the specificity was 95.86%, the accuracy was 95.50%, the positive predictive value was 82.05% and the negative predictive value was 98.78%. The method can be used to evaluate the state of the leukaemia, and to monitor the effect of treatment. PMID- 1643388 TI - One-step preparation of Hageman factor fragment concentrate. AB - The Hageman factor fragment (HFf) concentrate was prepared from acetone and dextran sulphate activated human plasma by chromatography on a CM-Sephadex column. The preparation was free of the main kallikrein inhibitors--Cl inactivator, alpha 2-macroglobulin, antithrombin III and alpha 1-antitrypsin. The HFf concentrate can serve as an activator of prekallikrein in patient plasma. PMID- 1643389 TI - TLC separation of certain tetracycline and amino glycopeptide antibiotics. AB - The separation of tetracycline and amino glycopeptide antibiotics was achieved on silica gel thin layers. Tetracycline antibiotics were resolved on a Co+2 (1.0%) impregnated silica gel layer using ethanol:acetic acid:water (10:6:6, v/v/v) as the mobile phase. Amino glycopeptide antibiotics were separated on an untreated silica gel layer using the mobile phase n-butanol:formic acid:water (6:5:7, v/v/v). The spots of these antibiotics were located by exposing the chromatoplate to iodine vapours. PMID- 1643390 TI - Liquid chromatographic determination of hyoscine (scopolamine) in urine using solid phase extraction. AB - A sensitive method for the determination of hyoscine (scopolamine) in urine is described. After concentration and "clean-up" on C18 and CN solid phase extraction columns, hyoscine was quantified by high performance liquid chromatography with coulometric detection (oxidation at +0.9 V). The limit of detection was 5 ng per sample and the precision for 5 mL samples containing 2 ng/mL was 12.3%. The method was applied to urine samples collected from 12 volunteers wearing Scopoderm TTS patches. The mean excretion rate of unmetabolized hyoscine was 0.45 micrograms/h and 87% of the total hyoscine was present as conjugates. Apohyoscine (aposcopolamine) was identified as a urinary metabolite. The significance of this with regard to hyoscine assays is discussed. PMID- 1643391 TI - An improved method for isolation and identification of Zn-metallothionein from cadmium-induced rat liver. AB - Zn-metallothioneins (MT-1 and MT-2) were isolated and purified from Wistar rat liver induced by subcutaneous injection with cadmium chloride over a short time. Instead of Sephadex G-50 and DEAE Sephadex A-50, new chromatographic media produced by Pharmacia, Sephacryl S-200, S-100 and DEAE Sepharose Fast Flow were used in the purification of metallothioneins. The time required for purification with the new method was only 1/3 that required with the usual method and had the same purification effect and rate of recovery. The number of mercapto groups measured with modified Ellman's reagent and cysteine as standard is 20 in MT molecules. Zn and Cd concentrations in each fraction were measured by single sweep polarography rather than atomic absorption spectrophotometry. MT-1 and MT-2 contained 6 gram atoms of zinc, but no cadmium. Purified MT-1 and MT-2 were shown by high performance liquid chromatographic analysis to be highly homogeneous and had an amino acid composition similar to that of Cd-MT. PMID- 1643392 TI - Isolation of human haemopexin in apo-form by chromatography on S-Sepharose Fast Flow and Blue Sepharose CL-6B. PMID- 1643393 TI - Depressed affect as a predictor of increased desire for alcohol in current drinkers of alcohol. AB - Male drinkers (n = 45) were asked to rate their desire for a drink of alcohol when presented with the sight, smell and taste of their preferred alcoholic beverage and of a lemon cordial drink. The subjects' level of depressed affect on that day and their average daily consumption of alcohol over the last 30 days were measured prior to exposure to these cues. Both level of depressed affect and log of mean daily alcohol consumption predicted increased desire for alcohol when alcohol cues were present, accounting for 40% of the variance in desire. When presented with the lemon cordial cues only 14% of the variance in desire for alcohol was explained by these variables. Also, Spearman's rank order correlations were calculated between heavy drinkers' (n = 19) ratings of self efficacy to resist drinking and desire for alcohol in the presence of the alcohol cues. There were significant negative correlations between desire for alcohol and self-efficacy ratings on the 'urges and temptations' and 'positive social situations' subscales of the Situational Confidence Questionnaire-39. Several alternative accounts of these findings are discussed. PMID- 1643394 TI - Reversibility of alcohol-induced immune depression. AB - Alcohol abusers have suppressed cellular immune function. The aim of the study was to investigate the time of sobriety required to normalize immune function. Delayed hypersensitivity was investigated during disulfiram controlled abstinence in ten heavy alcoholics and in seven moderate drinkers without liver diseases. For comparison a control group of eight previous drinkers was tested. The skin test responses were modest initially with a median area of response of 12 mm2 (range 0-31) in the heavy alcoholics and 3 mm2 (0-15) in the moderate drinkers. It improved significantly in both groups after two weeks of sobriety. The responses stabilized after 8 weeks at 74 mm2 (54-102) in the heavy alcoholics and after 9 weeks at 63 mm2 (42-76) in the moderate drinking group. The control group had skin test responses of 70 mm2 (46-87), not different from the responses of the alcohol groups after two months of abstinence. The results suggest that while 2 weeks of abstinence from alcohol will improve the depressed cellular immunity, 2 months of sobriety is necessary to normalize it. PMID- 1643395 TI - Drinking context and other influences on the drinking of 15-year-old New Zealanders. AB - This study investigated the influence of the situational characteristics of the drinking setting and a number of parental, personal and demographic variables on adolescents' alcohol use. The sample were 15-year-old participants in a multidisciplinary longitudinal study carried out in New Zealand. Measures of alcohol consumption were self reported amount of alcohol consumed on the most recent drinking occasion and amount usually consumed. All of the situational variables investigated had an effect on the amount of alcohol consumed on the most recent occasion. Greater amounts of alcohol were consumed if the alcohol was obtained from peers or by the 15-year-olds themselves, if the drink was consumed away from their own home, in the presence of peers only, and during the evening. More money to spend each week and lower SES were also associated with reports of greater alcohol consumption on the most recent drinking occasion. Adolescents with female friends who approved of drinking reported greater amounts of alcohol, the effect of female friends was most marked in the lower amounts reported by males who had female friends that disapproved of drinking. For amount of alcohol usually consumed, reports of larger amounts of alcohol were associated with more money available to spend each week and with lower SES. Furthermore, both males and females reported greater usual amounts if their male friends approved of drinking; female friends' approval was associated with greater amounts of alcohol usually being consumed, this effect was strongest for males. Sixty-eight per cent of the 15-year-olds indicated that they thought they definitely or probably would get drunk in the future. PMID- 1643396 TI - Increased desire to smoke during acute stress. AB - Conditions which promote smoking urges, or desire to smoke, are believed to be important in maintaining smoking behaviour, yet little controlled research has examined acute situational factors which increase desire to smoke. In this study, 16 male and 16 female smokers either smoked or sham-smoked with an unlit cigarette after brief abstinence during two sessions, one involving a stressful computer task and the other a non-stress task. Desire to smoke was greater during the stress vs. non-stress task for sham-smokers (p less than 0.01). Furthermore, although smoking desire decreased markedly after smoking in the smoking smokers (p less than 0.001), even this group tended to report greater desire to smoke during stress (p less than 0.10). There were no differences between males and females. These findings indicate that exposure to stressors increases desire to smoke, and suggest that such situations may be influential in maintaining smoking behaviour in smokers not attempting to quit. PMID- 1643397 TI - Drug and alcohol medical education: evaluation of a national programme. AB - In recognition of inadequacies in drug and alcohol medical education, funds were allocated to all Australian medical schools in 1988 to appoint co-ordinators to develop and implement drug and alcohol curricula. This programme was broadly modelled on the Career Teacher Programme successfully implemented in North America in the 1970s and early 1980s. During 1989 all but one of Australia's 10 medical schools made drug and alcohol co-ordinator appointments. Appointees came from diverse backgrounds including general practice, psychiatry, internal medicine, psychology and social work. The present study is a process evaluation and forms the first examination of the programme. Overall, findings indicated the programme to have achieved a 158% increase in drug and alcohol teaching hours, a 383% increase in the number of electives and a 109% increase in student places for electives. These effects occurred even though the average duration of co ordinators' appointments was only 15 months. Implications of these recent developments are discussed in terms of teaching strategies, clinical experience and the inclusion of key educational issues such as early intervention. Recommendations are made for a continuation of the programme and for future outcome evaluation. PMID- 1643398 TI - Treatment dependence: preliminary description of yet another syndrome. AB - The last decade has witnessed an expansion of treatment services and research into alcoholism and addiction. As so often happens when attempting to find solutions to pressing individual and social problems, the solutions have come to acquire an importance of their own, obscuring the problems they were intended to solve. Many programmes are characterized by stereotyped approaches to treatment, which seem more in line with the needs of the staff than with the problems of the clients. The hopes that treatment for addictions will solve some of the problems of contemporary society have given treatment a salience which cannot be justified in terms of results. Frustrated at the results of treatment, clinic staff intensify their efforts and attribute the shortcomings of treatment to a lack of client motivation. There are disconcerting parallels between these behaviours in clinicians and the behavioural changes of the Alcohol Dependence Syndrome. The label 'Treatment dependence syndrome' is proposed to characterize a pattern of individual and institutional behaviour which is both self-perpetuating and self defeating. PMID- 1643399 TI - Obstacles to effective alcohol policy in the workplace: a case study. AB - Based on a case study of an assembly plant in a large US corporation, this paper reports on cultural and environmental influences on the form and process of workplace alcohol policy. Utilizing both ethnographic and survey methods, research findings indicate that although alcohol policies are in place, management and union leaders are unclear about their source and content, and the general employee population perceives alcohol availability and on-job drinking as poorly controlled. In grounded theory fashion, two conceptual themes are employed for organizing empirical explanations of the weakened policy and under-controlled drinking. These are: (1) the dual alcohol policy dilemma, and (2) the union management debate over authority to discipline. The ambivalent nature of alcohol policy and organizational mechanisms involved in its implementation become risk factors for developing workplace-related alcohol problems. PMID- 1643400 TI - Drug abuse related emergency room episodes in the United States. AB - Drug-related hospital emergency room cases provide one measure of the morbidity associated with drug abuse. Over time, they indicate if problems associated with particular drugs are increasing or decreasing. These trends may be influenced by a number of factors including increased prevalence of use, increased dosages, increased potency, increased frequency of use, the aging of drug addicts, the use of more dangerous routes of administration, and the combined use of two or more drugs. The primary source of this information in the United States is the Drug Abuse Warning Network (DAWN). This paper will present statistics on the drug related emergencies reported to the DAWN system for 1989 and 1990. In addition to numbers of drug-related emergencies, this paper includes the population based rates for drug-related emergencies in 1990. PMID- 1643401 TI - Cocaine users in Amsterdam. PMID- 1643402 TI - Opium-tea and prevalence of HIV-1 infection among intravenous drug users in Vienna, Austria, 1986-1991. PMID- 1643403 TI - International comparisons of drink units. PMID- 1643404 TI - Tobacco advertising bans cut smoking. PMID- 1643405 TI - The Fifth Thomas James Okey Memorial Lecture: research and practice: the necessary symbiosis. AB - What relationship should exist between research and practice in the field of addictive behaviour? Are the perspectives essentially independent, or is there a necessary interaction? The extent of productive interaction is considered in three examples; (i) detoxification, (ii) stable abstinence, and (iii) goals other than abstinence. Changes are occurring in the drugs being used, the extents and types of associated co-morbidity, the levels of public and professional concern, and the explanatory paradigms which are dominant; and so it will be increasingly important for both practitioners and researchers to be sensitive and reactive to these changing circumstances. The most productive state for both research and practice will exist when they both feed off, and feed into each other--when there is indeed a necessary symbiosis. PMID- 1643406 TI - Providing drug injectors with easier access to sterile injecting equipment: a description of a pharmacy based scheme. AB - In this short paper we describe the operation of a pharmacy-based scheme operating in Glasgow to provide injecting drug users with sterile injecting equipment. The operation of the scheme is described under a number of headings: its physical location, the policy of selling injecting equipment, the return of previously used equipment, counselling and referral, and, the style of working of pharmacy staff. It is shown that while retail pharmacies may be an important point of contact with injecting drug users it should not be assumed that pharmacy staff already possess the requisite skills for working in this area. There is a need for pharmacists' and their staff to be able to draw upon the experience of colleagues working in this area in order to benefit from a pool of common experience. In addition there is a need to provide staff with access to appropriate back-up and support services. PMID- 1643407 TI - Life-style factors and social circumstances of syringe sharing in injecting drug users. AB - Measures taken to reduce HIV risk by injecting drug users have been reported in many countries, but a minority of injectors continue to engage in risky practices. In an ongoing cohort study, 207 drug injectors were interviewed and anonymously tested for HIV antibodies in saliva in 1989. Injectors reporting recent syringe sharing were compared with those not recently sharing; injecting events where sharing did and did not take place were examined. Those recently sharing syringes differed significantly from the non-sharers on several factors, including: use of heroin, dihydrocodeine and temazepam; injection of heroin, temazepam and prescribed methadone; accommodation and contact with other injectors; means of financial support and recent involvement in crime; secondary sources of injecting equipment and unsafe disposal; employment of HIV protective strategies; treatment contact with general practitioners; number of sexual partners and injecting status of sexual partners. The two groups were not significantly different in terms of attendance at syringe-exchange schemes and self-reported HIV antibody status. Syringe sharing would appear to be related to social circumstances and life-style factors rather than just individual choices and motivation. PMID- 1643408 TI - Diversity in primary structure and function of neuronal nicotinic acetylcholine receptor channels. AB - Neuronal nicotinic acetylcholine receptors are oligomeric protein complexes whose component subunits are each encoded by a family of homologous genes. The current challenge is to determine the functional contributions of the related subunits to the receptor-linked ion channels they compose and to uncover the physiological impact of the distinct channel classes expressed in vivo. In the past year, new approaches to the analysis of these receptors have yielded important insights into their stoichiometry, pharmacology and functional properties. PMID- 1643409 TI - G-protein-coupled receptors: the new dopamine receptor subtypes. AB - The family of genes encoding G-protein-coupled dopamine receptors continues to grow with the recent cloning of a fifth member. The availability of these clones has revolutionized the dopamine receptor field. Expression of individual dopamine receptors is permitting the detailed analysis of their pharmacology and coupling to second messenger systems, while probes based on the receptors' nucleotide sequences are being used to gain new insights into their tissue distribution and genetics. PMID- 1643410 TI - The olfactory multigene family. AB - A novel multigene family has been identified that is likely to encode odorant receptors on olfactory sensory neurons. Further studies on this gene family are likely to shed light on the molecular mechanisms underlying information coding in the mammalian olfactory system. This review is also published in Current Opinion in Genetics and Development 1992, 2:467-473. PMID- 1643411 TI - Neuronal Ca2+ signalling takes the local route. AB - The past year has seen several sets of experimental results demonstrate that fast, large and highly localized rises in intracellular Ca2+ concentration can occur in neurons. These results confirm previous theoretical predictions of acute spatial compartmentalization of Ca2+ signalling, and document a form of signalling that may occur whenever rapid and local signal processing is the goal. The dimensions involved present severe challenges for attempts to directly measure these signalling events. PMID- 1643412 TI - Exocytosis and its control at the synapse. AB - Several new approaches have given fresh insight into the mechanism and control of exocytosis. Electrophysiological and morphological studies show that many or all of the intramembrane particles at presynaptic active zones are voltage-gated Ca2+ channels. The sensitivity and time resolution of voltammetry allow the time course with which a single vesicle releases transmitter to be studied. Membrane proteins of the cell surface and synaptic vesicles have been shown to interact, and may join to form the fusion-pore complex. PMID- 1643413 TI - Neuromodulation. AB - The ability of the nervous system to respond to the environment and to learn depends upon the tuning of neuronal electrical activity, loosely called neuromodulation. The substrates for electrical activity and, therefore, neuromodulation are ion channels which may be either synaptic or extrasynaptic. Neuromodulation is dynamic and most frequently involves neurotransmitters and hormones acting via G-protein-coupled pathways. PMID- 1643415 TI - Signalling mechanisms. PMID- 1643414 TI - Synaptic plasticity: long-term potentiation in the hippocampus. PMID- 1643416 TI - Analysis by in situ hybridization of cells expressing mRNA for tumor-necrosis factor in the developing thymus of mice. AB - We have used in situ hybridization to investigate the expression of TNF-alpha genes by thymic cells during fetal development in mice. In 14-day-old fetal thymuses, very scarce cells produce TNF-alpha mRNA. A second phase of cytokine gene expression starts on day 16. The density of positive cells progressively increases up to day 20. Thymuses at 15 days of gestation and after birth do not express detectable cytokine mRNA. In an attempt to identify the nature of the TNF alpha mRNA-producing cells, acid phosphatase activity, which is characteristic of the macrophage lineage, was studied in the same thymuses. Acid phosphatase positive cells only appear on day 15. Their frequency increases up to birth. However, no correlation can be established between acid phosphatase--and TNF alpha mRNA--positive cells. The results indicate that a small subset of thymic cells is responsible for TNF-alpha mRNA production during ontogeny: These cells are not yet identified. The possible role of TNF-alpha in thymic ontogeny is discussed. PMID- 1643417 TI - Susceptibility of thymocytes for infection by chicken anemia virus is related to pre- and posthatching development. AB - To investigate the age-dependent mechanism of susceptibility for chicken anemia virus (CAV) infection, we inoculated embryos and chickens of ages between day 9 of embryonic development and day 28 after hatching with CAV. Chicken embryos inoculated at days 9 and 11 of development showed no CAV-infected cells in the thymus, nor in other lymphoid organs. Many CAV-infected cells were detected in the thymic cortex of all chicken embryos inoculated at days 13 and 16 of development and of all chickens inoculated 1, 3, and 7 days after hatching. All embryos and chickens that contained CAV-infected cells in the thymus also contained CAV-infected cells in the bone marrow, but not in the bursa of Fabricius or the spleen. In chickens inoculated at days 14 and 21, only few CAV infected cells were detected in the thymus, whereas these cells were not detected in thymi of 28-day-old inoculated chickens. Depletion of the thymic cortex was only detected in chickens inoculated from day 16 of embryonic development till day 21 after hatching. Only hematocrit values of the chickens inoculated 1 and 3 days after hatching were below normal. The rationale for the simultaneous susceptibility of cells of the T-cell lineage and cells of the erythrocyte lineage is discussed. As far as the thymus is concerned, the absence of clinical and microscopical signs of CAV infection in older chickens and the inability of CAV to infect embryos at days 9 and 11 of embryonic development may be caused by a lack of susceptible thymocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1643418 TI - Interferon gamma alters the phenotype of rat thymic epithelial cells in culture and increases interleukin-6 production. AB - Rat thymic epithelial cells (TEC) in long-term culture were characterized by anticytokeratin monoclonal antibodies (mAbs) and electron microscopy. Phenotypic analysis performed by a large panel of mAbs showed that the highest percentage of these cells was of the subcapsular/medullary type. Recombinant rat interferon (IFN)-gamma up-regulated class-I and class-II MHC expression by TEC in culture as confirmed by immunohistochemistry and flow cytometry, but did not significantly alter other cell markers. TEC supernatants of IFN-gamma-treated cultures showed higher interleukin-6 (IL-6) activity, compared to the control, as determined by proliferation of the IL-6-sensitive B9-cell line. Increased IL-6 activity was probably not a consequence of increased TEC number in IFN-gamma-treated cultures because IFN did not significantly stimulate TEC proliferation in vitro. In contrast, IL-6 significantly stimulated TEC proliferation, indicating that this cytokine is not only a regulatory molecule for T-cell proliferation, but could also be an autocrine growth factor for thymic epithelium. PMID- 1643419 TI - A novel adhesion molecule in the murine thymic microenvironment: functional and biochemical analysis. AB - The rat monoclonal antibody (mAb) 4F1, raised against mouse thymic stromal cells, recognizes cortical epithelium in tissue sections of mouse thymus; however, in flow cytometry, activated leucocytes (T cells, B cells, and macrophages) and transformed thymocytes are also positive for the 4F1-antigen (4F1-Ag). Western blotting, under both reducing and nonreducing conditions, demonstrates that the molecule to which 4F1 binds is expressed in four forms, 29, 32, 40, and 43 kD, all of which carry N-linked carbohydrate; and that the structure is identical on epithelium and lymphocytes. The 4F1-Ag on cortical epithelium is partially sensitive to PI-PLC treatment, whereas on transformed epithelial and lymphoid cell lines, it was resistant to this enzyme. The molecule, therefore, may exist in both transmembrane and phosphoinositol-linked forms. In functional blocking experiments, mAb 4F1 gave inhibition of both T-cell proliferation in MLR and of cytotoxic T-cell killing of alloantigenic targets; it also blocked adhesion of transformed thymocytes to thymic epithelial cells in vitro. These molecular and functional characteristics suggest that the 4F1-Ag is a novel adhesion molecule that may be involved both in intrathymic T lymphocyte differentiation and in peripheral T-cell function. PMID- 1643420 TI - Pathogenetic significance of fetal-type acetylcholine receptors on thymic myoid cells in myasthenia gravis. AB - To investigate the role of thymic myoid cells in the pathogenesis of myasthenia gravis (MG), mRNA of nonneoplastic thymuses from eight MG patients was analyzed by dot blot hybridization for the occurrence of acetylcholine receptor (AChR) subunit transcripts, using the five AChR-subunit cDNAs (alpha, beta, gamma, delta, and epsilon) as probes. Attention was particularly paid to the gamma- and epsilon-subunit transcripts that specify fetal- or adult-type AChR. In all eight thymuses, transcripts of the alpha-, beta-, gamma-, and delta-subunit genes were detected. Relative autoradiographic signal intensities correlated with the frequencies of thymic myoid cells as determined by immunostaining with anti-AChR monoclonal antibodies. In only one of these thymuses were transcripts of the epsilon-subunit gene detected in addition to those of the other subunit genes. Four MG-associated thymomas without myoid cells were devoid of any AChR-subunit mRNA. Our findings imply that fetal-type AChR is expressed in MG thymuses as a rule, whereas adult-type AChR is coexpressed with it only in a minority of cases. A similar pattern of cotranscription is known to occur at certain stages of muscle development, and can be found in human rhabdomyosarcomas with an intermediate stage of myogenesis. Because the serum autoantibodies of MG patients exhibit preferential reactivity with fetal AChRs, the presence of fetal AChRs in the thymus provides circumstantial evidence for an active involvement of thymic myoid cells in the autoimmune process. PMID- 1643421 TI - Synthesis and cytotoxic properties of new N-substituted 4-aminophenol derivatives with a potential as antimelanoma agents. AB - New tyrosinase-targeted compounds based on structural variants of the prototype unit 4-aminophenol have been synthesized and screened for their potential as antitumour agents against malignant melanoma. Cytotoxicity assays showed that N-4 hydroxyphenylglycine (NHPG) and its alpha-methyl derivatives methylphenylglycine and dimethylphenylglycine exhibit significant antiproliferative effects on pigmented human melanoma cell lines (HBL), with inhibitory concentrations at 50% (IC50) around 80 micrograms/ml. A marked increase in cytotoxicity was observed with morpholine-containing 4-aminophenols, e.g. N-(2-morpholinoethyl)-4 aminophenol, which showed an IC50 of 20 micrograms/ml of HBL cells. Much more pronounced was the effect of the diacetoxy-derivative, DiAcMoAc, which showed an IC50 of 15 micrograms/ml on HBL cells and as low as 2 micrograms/ml on tyrosinase containing, non-pigmented human melanoma cells (LND1), with a toxicity response of the same order of magnitude as that of melphalan. These results open interesting perspectives in the design of new targeted pro-drugs against malignant melanoma. PMID- 1643422 TI - Role of asparagine-linked carbohydrates in pulmonary metastasis of B16-F10 murine melanoma cells: implication through glycosylation inhibition by nojirimycin. AB - N-linked oligosaccharide moieties of cell surface glycoconjugates may be involved in the metastatic potential of tumour cells. Many studies have examined the anti metastatic properties of inhibitors of carbohydrate synthesis or processing in vitro. However, there has so far been little evidence of such inhibitory factors on metastasis in vivo because of the general high toxicity of the inhibitors. In this study, we found nojirimycin (NM) to be a substantially non-toxic carbohydrate synthesis inhibitor that inhibited the experimental metastasis of B16-F10 melanoma cells not only in vitro but also in vivo. When NM was administered intraperitoneally to syngeneic C57BL/6 mice, the inhibition was dose dependent, with 40-75% suppression of pulmonary colonization observed after 5 days exposure to NM (at 0.4 or 4 mg/day). An in vitro lectin sensitivity assay showed that NM-treated B16-F10 cells were less susceptible to the lectin concanavalin-A, suggesting alteration or decrease of high mannose-type carbohydrate moieties on the cell surface. Further in vitro analysis of adhesiveness between B16-F10 cells and endothelial cells demonstrated that NM treatment causes reduced binding of B16-F10 cells to endothelial cells. We have also studied the effect of NM on natural killer (NK) cells in mice. NM treatment elicited no substantial increase in the cytotoxic activity of splenic NK cells against YAC-1 target cells. These results indicate that NM acts on the process of adhesion and that specific structures of the cell surface carbohydrate moieties may be involved in the colonization phase of metastasis in vivo. PMID- 1643423 TI - Topical retinoic acid augments ultraviolet light-induced melanogenesis. AB - Melanin, the natural pigment found in human skin, absorbs and protects against the ultraviolet (UV) components of sunlight. Melanin production (melanogenesis) is increased by exposure to sunlight, causing a darker skin colour which is regarded as aesthetically pleasing by many humans, who therefore expose themselves to large amounts of potentially damaging sunlight. We have found that topically applied all-trans retinoic acid, a metabolic derivative of vitamin A, greatly enhances UV light-induced melanogenesis: the same preparation on its own had no effect on skin pigmentation. An orally administered retinoid, temarotene, did not have this effect. These observations were made using a lightly pigmented mouse strain, HRA: Skh-2, and confirmed in 2 human volunteers. This is the first time that metabolic derivatives of vitamin A have been shown to augment UV light induced melanogenesis, suggesting a role for vitamin A in this process. PMID- 1643424 TI - Induction of interleukin-2, natural killer cell activity and anti-melanoma antibodies resulting from immunization of mice with formalinized extracellular antigens (FECA) of murine melanoma. AB - Extracellular products from melanoma cells may play an important role in the pathogenesis of metastatic melanoma. Studies were designed to evaluate the effect of vaccination with formalinized extracellular antigens (FECA) of murine melanoma cells (MMM B16-F10) on survival and immune response of C57BL/6 mice. The cellular immune response was evaluated by assessing interleukin-2 (IL-2) production and natural killer cell activity, whereas the humoral immune response was examined by measuring the production of specific antibodies to extracellular antigens (ECA). IL-2 production by the splenocytes from immunized animals was significantly higher (4.7 U/ml and 3.7 U/ml) than that of controls (1.38 U/ml). The splenocytes from immunized mice revealed significantly higher natural killer cell activity. Similarly, immunized animals responded by producing specific antibodies against the extracellular melanoma antigens as detected by ELISA. The peak production of antibodies against ECA was observed on the 21st day post-immunization. These results suggest that FECA are immunogenic and may enhance active cellular and humoral anti-melanoma immunity. PMID- 1643425 TI - Effect of epidermal Langerhans cells from melanoma patients on lymphoproliferative responses. AB - Langerhans cells (LC) are potent antigen-presenting dendritic cells essential for cutaneous immune responses. LC are reduced in number in the epidermis adjacent to primary melanomas and increase in number in the lymphoid infiltrate that accumulates in the dermis deep to such tumours. The present study was undertaken to assess whether the reduction in epidermal LC was accompanied by alterations in their functional competence. We evaluated the capacity of LC from melanoma patients to augment lymphocyte responses to phytohaemagglutinin (PHA), tetanus toxoid and melanoma-associated antigens. Using a panning method to bind Fc receptor positive (FcR+) cells we separated LC-enriched (FcR+) and depleted (FcR ) fractions of epidermal cells. Lymphocyte responses to PHA and tetanus toxoid were increased in the presence of LC-enriched cell populations, but not in the presence of LC-depleted epidermal cells. In preliminary experiments LC-enriched cell populations did not help initiate detectable in vitro lymphoproliferative responses to autologous metastatic melanoma cell lines, allogeneic HLA-DR+ metastatic melanoma cell lines, or a 180-190 kD melanoma tumour-associated antigen. Future studies will investigate the capacity of LC to augment responses to melanoma-associated antigens on autologous primary melanomas. PMID- 1643426 TI - A comparison of heat sensitivity, radiosensitivity and PLDR in four human melanoma cell lines. AB - Comparison of the heat sensitivity and radiosensitivity of four human melanoma cell lines in culture revealed a large variation in sensitivity amongst the four cell lines. Three of the four cell lines had large shoulders on the survival curves when exposed to hyperthermia (44 degrees C or 45 degrees C). These three cell lines also had demonstrable shoulders on the acute radiation dose response curves. The most radiosensitive cell line did not show a shoulder region in the heat or radiation survival curves (HT-144, Dq = 0.2 Gy). Despite this consistency in the presence or absence of shoulder, there was no correlation between heat and radiation sensitivity in the four melanoma cell lines. Furthermore, regardless of radiosensitivity, all four lines studied showed competent repair of potentially lethal damage. The recovery ratios at a surviving fraction of 0.001 ranged from 5.7 to 7.6. All four lines had a similar cell cycle distribution at the time of treatment, hence the variation observed in the response of these four lines to radiation and heat was not due to differences in cell cycle kinetics. Preliminary results of DNA polymerase-alpha and -beta activities do not demonstrate a clear correlation between cellular levels of these two enzymes and radiosensitivity. PMID- 1643427 TI - Multiple primary melanomas in a patient with familial-type DNS during clomiphene induced pregnancy. AB - A 35-year old woman developed six primary cutaneous melanomas during her third pregnancy. She had received clomiphene treatment for nearly 2 years previously. She developed two more primary melanomas 15 and 21 months after giving birth. All melanomas were histologically associated with preexisting dysplastic naevi. The patient showed the characteristic phenotype of the dysplastic naevus syndrome; a cousin and an aunt were treated for malignant melanoma and the patient's brother had histologically confirmed dysplastic naevi. The course of her first two pregnancies was not complicated by the development of melanomas. We suggest that clomiphene may have played a role in the activation or progression of these 'precursor lesions' into malignant melanoma. PMID- 1643428 TI - Malignant melanoma of the nasal cavity and nasopharynx treated with cisplatin and accelerated hyperfractionated radiation. AB - Primary malignant melanoma of the nasal cavity and paranasal sinuses is an uncommon disease, accounting for only 0.5-2% of all malignant melanomas. The primary treatment has been surgery. The frequency of local recurrence is high and recurrence is also the major determinant of treatment failure. Here we report on six patients with locally advanced disease, four of whom were too advanced for surgery, who were treated with accelerated hyperfractionated radiation in combination with cis-platinum. Three of four patients treated for local recurrent disease achieved a local cure and died of disseminated disease after 9-21 months. One patient given preoperative cisplatin and radiation is still alive with no evidence of disease 34 months after the completion of treatment. The present protocol may be a useful approach to obtain local control with the possibility of long-term cure. PMID- 1643429 TI - Modulation by interferon alpha and gamma of the expression of a melanoma associated antigen detected by autologous antibody. AB - Interferons (IFN) are known to alter the expression of histocompatibility and tumour-associated antigens. We have reported the isolation and purification of a 66-kD melanoma-associated antigen (MAA) that is recognized by the host. Competitive binding with MAA reduced autologous antibody binding to five melanoma cell lines, suggesting that a similar antigen is detected by other patients with melanoma. Nine melanoma cell lines were incubated for 3 days with 0.01-100 units/ml of interferon alpha (IFN-alpha) or interferon gamma (IFN-gamma) and the maximum titre of autologous antibody reactivity was determined by protein A haemadsorption. Incubation with IFN-alpha or IFN-gamma resulted in a decrease in maximum titre of autologous antibody reactivity directed against all melanoma cell lines. A 3-day incubation of three melanoma cell lines with IFN-gamma augmented the expression of HLA-DR, as has been reported by others. Incubation with spent media from autologous melanoma cells exposed to IFN-alpha inhibited autologous antibody binding less than control media from melanoma cells to which no IFN was added, indicative of decreased production or internalization of MAA. Conversely, incubation with spent media obtained after exposure to IFN-gamma inhibited autologous antibody binding to a greater degree than control spent media, consistent with increased shedding of antigen. These results suggest that IFN-alpha and IFN-gamma down-regulate the expression of MAA detected by autologous antibody by different mechanisms of action. PMID- 1643430 TI - Defect of insulin receptor in insulin-resistant variants of Cloudman S91 mouse melanoma cells. AB - To study the mechanisms by which insulin regulates proliferation, we have compared wild-type Cloudman melanoma cells, whose growth in inhibited by insulin (insinh) to variant lines that were genetically selected for resistance to insulin (insres). Scatchard analysis of insulin binding to five insres) lines and six insres variants revealed a marked reduction in the number of high-affinity binding sites for insulin in the insres lines, and insres lines displayed an abnormal beta-subunit of the insulin receptor. During autophosphorylation of the wheat germ agglutinin-purified receptor, the beta-subunit apparently underwent proteolytic degradation. This proteolysis was ATP-dependent and was prevented by bovine pancreatic trypsin inhibitor, and phenylmethylsulphonyl fluoride, but not by aprotinin or leupeptin. Receptor proteolysis was not observed in wild-type lines. The results suggest that insulin resistance in the mutant Cloudman melanoma cells is apparently due to proteolysis of the beta-subunit of insulin receptor which, in turn, alters insulin binding capacity of the cells and blocks their anti-proliferative response to the hormone. PMID- 1643431 TI - Can oncogene (RAS) activation predict susceptibility of human melanoma to activated lymphocytes and, therefore, the clinical response of such neoplasms to adoptive immunotherapy? AB - The expression of activated ras oncogenes was found to be associated with that of tumour-specific transplantation antigens in mouse tumours, which can be cured by adoptive immunotherapy with T lymphocytes and interleukin-2 (IL-2). A similar association is here proposed to exist between RAS oncogene activation (mutation) in human melanoma and susceptibility of these tumours to the lytic action of activated lymphocytes (both lymphokine-activated killers and cytotoxic T cells) which have been used, along with IL-2, in the adoptive immunotherapy of advanced melanomas. The limited clinical response (15-25%) of melanoma patients to different immunological therapies is, therefore, considered to be due to a similar frequency of immunogenic, RAS+ melanomas. The authors thus suggest that RAS activation might be a marker of immunogenicity and that only the subset of melanoma cells expressing activated RAS will in turn possess tumour antigens which can be the target of immunotherapeutic, activated lymphocytes. It is then predicted that RAS+ melanomas will be more susceptible to adoptive immunotherapy than RAS-counterparts. PMID- 1643432 TI - Are advanced malignant melanoma cells hybrids between melanocytes and macrophages? PMID- 1643433 TI - Keystone symposium. Melanoma and biology of the neural crest. Taos City Hall, Taos, New Mexico, USA, 1-8 February 1992. PMID- 1643434 TI - Risk factors for melanoma: site variation in minimal erythema dose. AB - Skin types 1 and 2, increased numbers of moles, and excessive intermittent sun exposure are known risk factors for cutaneous melanoma, but the inter relationship between UV radiation exposure, moles and melanoma remains unclear. There is a noteworthy site variation in melanoma, it being more common on the lower leg in women and on the back in men. In order to determine whether this site variation could provide further clues to the pathogenesis of melanoma, we examined site variation in photosensitivity and its relationship to other known melanoma risk factors (number of moles, skin type and skin colour) in 25 healthy volunteers. A marked site variation in photosensitivity was found. The pale skin of the volar aspect of the forearm was markedly less photosensitive than the darker skin of the back. Females were more photoresistant than males on the lower legs even though this is the more common site for melanoma in women. There was some correlation between the number of moles and photosensitivity at the two sites. PMID- 1643435 TI - The prognostic significance of histologic regression in cutaneous melanoma. AB - A retrospective evaluation of 201 stage I cutaneous melanomas was performed to investigate the prognostic significance of histological regression (present in 67 cases). Thin melanomas showed regression more frequently than thick lesions (48% less than or equal to 0.75 mm vs 12% greater than 3 mm). The mean disease-free interval was 33.53 months in regressing tumours and 19.9 in non-regressing tumours (p = 0.07): differences between the survival curves were not significant (p = 0.61). Metastases developed in 13 (19.40%) patients with regressing tumours and by 40 (29.85%) patients with non-regressing tumours. Although we observed a higher frequency of regression in thin melanomas we could not demonstrate an influence of regression on disease-free interval and survival. PMID- 1643436 TI - The tape stripping toluidine blue (TSTB) method in the diagnosis of malignant melanoma: an investigator-blind study. AB - The cytological investigation of the skin surface with the simple, non-invasive tape-stripping toluidine blue (TSTB) method has been proposed to improve the clinical diagnosis of many dermatological disorders. We carried out an investigator-blind study to estimate the sensitivity and specificity of the procedure for the diagnosis of malignant melanoma. One hundred and fifty pigmented lesions were tested. Positive results were obtained in 22 out of 32 malignant melanomas (sensitivity 68.7%), with three false negatives (two cases of lentigo maligna in premalignant phase and one early melanoma in situ) and seven non-significant findings. Negative results were found in 88 out of 118 non melanoma conditions (specificity 74.5%), with three false positives (two Spitz's naevi and one dysplastic naevus) and 27 non-significant findings. Thus the TSTB method may be a helpful diagnostic tool, in addition to the ABCDE rule, for the early detection of malignant melanoma. PMID- 1643437 TI - Characterization of isoforms of the major allergen Phl p V by two-dimensional immunoblotting and microsequencing. AB - Timothy pollen extract was separated by 2D PAGE blot for further characterization of the major allergen Phl p V. Using pooled patient serum, we demonstrated that Phl p V consists of 4 components at 32 kD and 4 components at 38 kD, each differing in their pIs. The primary structure and the amino acid composition of the 8 proteins were determined form the blotted samples. Proteins of the same molecular weight did not differ in the 20 N-terminal amino acid residues, whereas the 32- and 38-kD proteins showed only 60% sequence identity. Furthermore, the results of the amino acid analyses suggest differences in their protein structure. Therefore, it might be possible that both proteins express different IgE-reactive epitopes. PMID- 1643438 TI - Detection of house dust mite (HDM)-specific IgE antibodies on nasal mast cells from asthmatic patients whose skin prick test and RAST are negative for HDM. AB - Mast cells are found in nasal smears of pediatric patients with perennial bronchial asthma whose skin prick test and radioallergosorbent test (RAST) are negative for inhalant allergens. IgE antibodies were demonstrated on these mast cells by monoclonal anti-human IgE antibodies, whereas IgG antibodies were not detected by monoclonal anti-IgG antibodies. In order to pursue the causative allergen for asthma in these patients, binding potential between IgE antibodies on nasal mast cells and house dust mite (HDM), the most prevalent aeroallergen, was examined by an immunochemical technique. Out of 9 patients whose skin prick test and RAST were negative for HDM, 7 were found to have HDM-specific IgE antibodies on their nasal smear mast cells. None of these 7 patients had IgE antibodies to cedar pollen, a negative control aero-allergen, on their mast cells. Specific binding of HDM on the mast cells was further confirmed by the fact that nasal mast cells from patients with egg allergy bound egg white but not HDM on their surface. Preincubation of mast cells with anti-IgE antibodies inhibited binding of HDM on the mast cells, indicating that HDM was bound to surface IgE antibodies on the mast cells. These experiments enabled us to expeditiously identify sensitization to an inhalant allergen, such as HDM, in young asthmatic patients whose allergen cannot be found by conventional laboratory diagnostic procedures. PMID- 1643439 TI - Expression of the calcium-binding proteins MRP8 and MRP14 by early infiltrating cells in experimental contact dermatitis. AB - The immune response to an allergen is not only dependent on the inflammatory stimulus, but also on the genetic disposition of the individual. Important effector cells in the immune response are myelomonocytic cells in their various differentiation stages. We recently described the expression of MRP8 and MRP14, two calcium-binding proteins of the S-100 family, by these cells during inflammatory activation. Here, we investigated whether their expression in murine contact dermatitis is dependent on the stimulus by which dermatitis is elicited, and if it is related to the genetic constitution of different inbred strains of mice. Therefore we performed immunohistochemical studies on the distribution of MRP8- and MRP14-positive cells during experimentally induced allergic (ACD) and irritant contact dermatitis (ICD). Both forms of dermatitis were elicited in BALB/c and C57B1/6 mice. BALB/c mice were found to react with a more intense inflammatory response in both ACD and ICD (high responders) than C57Bl/6 mice (low responders). The expression of MRP8 and MRP14 in both forms of dermatitis correlated with the early influx of macrophages and with the cell density of the infiltrate. Also the percentage of MRP8- and MRP14-positive cells in the infiltrate during ACD or ICD was higher in the more intense inflammatory reaction of BALB/c mice compared to C57Bl/6 mice. We conclude that MRP8 and MRP14 define a differentiation stage of inflammatory macrophages and that their expression correlates with the activity of inflammatory processes. PMID- 1643440 TI - Modulation of anti-tumor cytotoxicity of cultured mast cells by metabolic inhibitors. AB - IL-3-dependent, murine mast cell lines derived from embryonic yolk sac precursors display a tumoricidal activity that is blocked by antibodies against tumor necrosis factor-alpha, indicating that this cytokine is the major mediator involved in the cytotoxic activity of the cultured mast cell lines. Further, cholera toxin strongly inhibits the cytotoxic activity of mast cells as well as their IL-3-induced DNA synthesis response but not IgE-mediated serotonin release. Cyclosporin A diminished cytotoxicity and serotonin release, but not DNA synthesis. Actinomycin D markedly suppressed the cytotoxicity of one mast cell line but only slightly suppressed that of another, whereas the IL-3-induced proliferation of both mast cell lines was strongly inhibited. Thus, our studies indicate that the cytotoxic function of mast cells is relatively independent of their degranulation and proliferation and may utilize different signalling pathways. PMID- 1643441 TI - Human gut mucosal mast cells: ultrastructural observations and anatomic variation in mast cell-nerve associations in vivo. AB - One hundred and seventeen coded intestinal biopsy specimens were examined by electron microscopy. All surgical biopsies were obtained from uninvolved sites of patients with two inflammatory bowel diseases (ulcerative colitis or Crohn's disease) and from patients with preneoplastic and neoplastic diseases (adenocarcinoma, rectal polyp, familial polyposis). Biopsy sites included normal ileum, colon, and rectum as well as conventional ileostomies and continent pouches constructed from the ileum. The data reported here describe the ultrastructural anatomy of human gastrointestinal tract mucosal mast cells in vivo and their anatomic associations with enteric nerves. PMID- 1643442 TI - Long-term cultured mouse mast cells: ultrastructure, histamine and leukotriene levels. AB - Interleukin 3 (IL3), dependent cells were obtained from bone marrow (9/10 experiments) and spleen cells (4/5 experiments), but not from the thymus. These cells were similar to mucosal mast cell toluidine blue staining and electron microscopy. They had heterogenous metachromatic granules, and some had large scroll-like structures. They also contained histamine (200-800 ng/10(6) cells) for the first 2-5 weeks, whose level diminished to less than 30 ng/10(6) cells by 10 weeks of culture. They also generated leukotriene (LT) C4/D4 (10-40 ng/10(6) cells) and LTB4 (2-5 ng/10(6) cells) for over 100 days of culture. In one experiment, bone marrow-derived mast cells after 150 days of culture began to produce an IL3-like substance and proliferated exponentially without exogenous IL3. PMID- 1643443 TI - N-terminal amino acid sequence homologies of group V grass pollen allergens. AB - In an earlier study, we presented data regarding the immunoaffinity purification and N-terminal sequencing of a major pollen allergen from orchard/cocks-foot grass (Dactylis glomerata), now identified as the group V allergen Dac g V. In this paper, we have extended our investigations to include group V allergens from other grass species. Our data confirm the presence of group V-restricted characteristic N-terminal amino acid sequences containing a high alanine and hydroxyproline (P') rather than proline (P) content, and based upon two conserved elements (ADAGY and TPA/TP'A). PMID- 1643444 TI - Recombinant allergens: biological, immunological and practical aspects. AB - Molecular and biochemical characterization of atopic allergens has made considerable progress since the application of cDNA cloning techniques. A number of mite allergens, a hornet venom allergen (Dol V), tree pollen allergens, grass pollen allergens and allergens from ragweed were cDNA cloned and sequenced. For the mite allergens Der p I and Der f I, a thiol protease activity can be assumed on the basis of sequence similarities with plant thiol proteases. The major birch pollen allergen, Bet v I, is highly homologous to a group of plant pathogenesis related proteins, suggesting a similar function of the pollen allergen for the birch tree. Finally, the minor birch pollen allergen, Bet v II was shown by sequence comparison and biochemical properties to represent the actin-binding protein profilin, a protein found in all eukaryotic cells. PMID- 1643445 TI - Profilin is a cross-reactive allergen in pollen and vegetable foods. AB - Sera with IgE antibodies against grass pollen often contain IgE against vegetable foods. We investigated the role of the ubiquitous protein profilin in this cross reactivity. Profilin was purified from Lolium perenne grass pollen by means of affinity purification with Sepharose-coupled poly(L-proline). This solid phase was also used as capturing agent for profilin from pollen and food extracts for application in a radioallergosorbent test. It was shown that profilin is an allergen in grass pollen and in a wide range of vegetable foods, like potato and celery. Within a grass-pollen-sensitive population, patients with IgE to vegetable foods have a high incidence of antibodies against profilin. IgE antibodies against grass pollen profilin were shown to be cross-reactive with respect to vegetable foods. PMID- 1643446 TI - For all the saints. PMID- 1643447 TI - A case for exit exams. PMID- 1643448 TI - Research priorities in rheumatology. PMID- 1643449 TI - Kinins--key mediators in inflammatory arthritis? AB - Recent evidence suggests an important role for kinins in the generation of pain, swelling and the cellular damage associated with inflammatory joint disease. Kinins are considered to be pro-inflammatory peptides for a variety of reasons. They stimulate c fibres in the synovium to cause pain and increase extravasation of fluid to produce swelling. Kinins possess the capacity to release neurotransmitters (substance P, acetylcholine) and a second wave of mediators (interleukin-1, tumour necrosis factor, interleukin-8, prostaglandins, leukotrienes). The steady levels and turnover of kinins is regulated by formation (enzymic action of kininogenases on endogenous substrates called kininogens) and by metabolism (kininases, peptidases that hydrolyse kinins). These components of the kinin system can enter the synovial joint space either by transudation from the plasma or from degranulating neutrophils chemotactically attracted into the synovium from which they migrate into the synovial fluid. If kinins are involved, one would expect neutrophil derived mediators of the system to dominate in rheumatoid arthritis and psoriatic arthritis and plasma derived products to be more important in osteoarthritis and gout. But, the question whether any of the functions attributed to each component of the system can be considered to be a primary factor in the cellular pathology of inflamed joints remains to be established. Future investigations, including therapeutic trials with kinin antagonists and kallikrein inhibitors, will need to address the differential role of the kallikreins and kinins in the different types of synovitis, on symptoms of inflammation and on any remedial effects on the progression of tissue damage within the joint. PMID- 1643450 TI - The prevalence of palpable finger joint nodules in diffuse idiopathic skeletal hyperostosis (DISH). A controlled study. AB - The presence of clinically palpable finger joint nodules (Heberden's and Bouchard's nodes) was documented in 123 consecutive cases with diffuse idiopathic skeletal hyperostosis (DISH) of the thoracic spine and 191 matched DISH negative controls. The prevalence of palpable finger joint nodules was almost twice as frequent in cases with spinal DISH compared to controls (46% versus 31%, chi 2 = 7.67, P less than 0.01; multivariate adjusted odds ratio OR = 1.84; 95% CI: 1.14 2.98). This increase was most marked at the proximal interphalangeal joint, in males and in patients up to the age of 65 years. In addition and independent of other variables such as hyperostotic features, age and sex, the prevalence of palpable finger joint nodules was about twice as high in probands with a history of physically heavy work compared to those without (43% versus 26%, chi = 9.18, P less than 0.005; multivariate adjusted odds ratio OR = 2.10; 95% CI: 1.26-3.52). From these results we conclude that DISH should be considered as an independent risk factor in the development of finger joint nodules. PMID- 1643451 TI - Cystic fibrosis arthritis. A report of five cases. AB - In a retrospective study of 206 patients with cystic fibrosis (CF), five cases of CF arthritis were recorded. This is a frequency of 2.5% and of 4.5% in patients aged over 10. Four patients had episodic arthritis, which was related to the course of pulmonary disease in two cases. In three patients, synovial fluid examination revealed minimal evidence of inflammation. In one of these three cases, synovial biopsy revealed a mild and non-specific synovitis. The fifth patient had chronic arthropathy and was positive for rheumatoid factor, but did not fulfil the criteria for rheumatoid arthritis. There were no radiographic abnormalities in any of these cases. CF arthritis is a rare syndrome of unknown pathogenesis. PMID- 1643452 TI - Abnormal temperature control suggesting sympathetic dysfunction in the shoulder skin of patients with frozen shoulder. AB - In view of the possibility that sympathetically mediated pain could be responsible for frozen shoulder symptoms we compared shoulder skin vasomotor control in 11 patients with frozen shoulder and 17 similarly aged normal subjects without shoulder pain. Using computer-assisted thermography the shoulder skin temperature was assessed before and following a 'cold challenge' which consisted of a 15 degrees C cold pack being held against the skin for 60 sec. Both prior to and immediately following the cold challenge shoulder skin temperatures tended to be lower in the patients. During a 10-min rewarming phase, however, the between group temperature difference increased and became significant at the 0.05 level. These abnormalities of temperature control in patients clearly suggest sympathetic dysfunction in the dermatome subserving pain sensation from the affected shoulder. Whether these abnormalities are primary or secondary remains unresolved. PMID- 1643453 TI - Gastrointestinal accumulation of indium-111 labelled granulocytes in reactive arthritis. AB - Six patients with reactive arthritis (ReA) were examined for gastrointestinal accumulation of Indium-111 labelled granulocytes. Abnormal scintigrams were found in three of six patients all of which showed early (less than 4 h) accumulation of indium-111 labelled granulocytes which may represent small intestinal inflammation. Our findings may indicate that the small intestine is involved in ReA, and that indium-111 granulocyte scintigraphy is a useful method for demonstrating inflammatory changes in the small intestine in reactive arthritis (ReA). PMID- 1643454 TI - A case of haemochromatosis arthritis. PMID- 1643455 TI - Transverse myelitis in systemic lupus erythematosus: two cases with magnetic resonance imaging. AB - Transverse myelitis is one of the most serious neurological complications occurring in the course of systemic lupus erythematosus. We describe two lupus patients, with transverse myelitis, one of whom had associated optic neuritis. In both, magnetic resonance imaging of the spinal cord showed an abnormal signal. In one case a good response to steroid and immunosuppressive therapy was observed; the other case failed to improve despite the therapy applied. PMID- 1643456 TI - Pseudoarthroplastic' hand in arthritis mutilans. AB - A 46-year-old man with arthritis mutilans and hand radiographic appearance suggestive of previous surgery is described. We propose the term 'pseudoarthroplastic' hand for this radiological finding. PMID- 1643457 TI - Anticardiolipin antibodies and a severe subset of systemic lupus erythematosus. PMID- 1643458 TI - The use of intranasal calcitonin in the treatment of algodystrophy. PMID- 1643459 TI - Confusional syndrome as the presenting form of calcium pyrophosphate dihydrate deposition disease. PMID- 1643460 TI - Short of a length:Streptococcus sanguis knee infection from dental source. PMID- 1643461 TI - Two cases of diffuse idiopathic skeletal hyperostosis and ankylosing spondylitis. PMID- 1643462 TI - Non-traumatic Clostridium septicum arthritis in a patient with caecal carcinoma. PMID- 1643464 TI - Dual publication--again. PMID- 1643463 TI - Vertebral osteoporosis in rheumatoid arthritis patients: effect of low dose prednisone therapy. PMID- 1643465 TI - Vanishing bile duct syndrome. PMID- 1643466 TI - Improving practice: the clinician's role. PMID- 1643467 TI - Prognostic factors in colorectal cancer. AB - The prognostic power of the extent of tumour invasion is indisputable; Dukes' classification has repeatedly been proven to be strongly correlated with patient survival. Modifications have led only to confusion, resulting in caution being required in the classification of patients with Dukes' A tumours. In the UK, the American tumour node metastasis and Australian clinicopathological systems are frequently considered too complex for routine clinical use. Meanwhile, Jass's classification may be complicated by observer variation between pathologists, and recent evidence suggests that it offers no advantage over that of Dukes. All the conventional staging systems also fail to take the skill of the surgeon into account when determining outcome. Attempts at quantifying tumour structure have not heralded the expected major advance. For instance, the expense and uncertain prognostic value of tumour DNA content assessed by flow cytometry are likely to restrict widespread use of this technique. It may soon be possible, however, to provide optimum treatment for patients based on individual tumour doubling times. Classification using knowledge of how a small number of cells in the tumour have the ability to invade locally, enter blood vessels and metastasize would also provide important prognostic information on which treatment could be based. Until then, the ease of use and high prognostic power of Dukes' classification ensure that, after 60 years, it is still the 'gold standard' against which all other prognostic classifications in colorectal cancer should be assessed. PMID- 1643468 TI - Nutrition and malignant disease: implications for surgical practice. AB - Malignant disease is often associated with weight loss and malnutrition. Nutritional support is frequently provided to patients with cancer in an attempt to improve nutritional status and reverse weight loss, with the aim of reducing morbidity and mortality rates. This review evaluates the effect of supplemental nutrition on morbidity and mortality in patients with malignancy undergoing treatment with surgery, chemotherapy or radiotherapy. It also assesses the effect nutritional supplementation has on host defence mechanisms and how nutrients affect tumour cell growth. The evidence suggests that perioperative nutritional support, if given for at least 10 days, reduces morbidity and mortality in patients with biochemical evidence of severe malnutrition, manifest as a low serum albumin concentration and excessive weight loss. In contrast, there is no evidence that parenteral nutritional support benefits patients undergoing chemotherapy or radiotherapy, in terms of either an increased tumour response rate or prolongation of survival. Current research on malignant disease is highlighting the role of specific nutrients (amino acids, essential fatty acids and polyribonucleotides) as key regulators of both anticancer host defence mechanisms and the control of nitrogen metabolism and tumour growth. Arginine, essential fatty acids and ribonucleotides have all been demonstrated to stimulate antitumour host defence mechanisms and some also modulate tumour cell metabolism. Dietary manipulation offers exciting possibilities for the innovative management of malignant disease. PMID- 1643469 TI - Use of Teflon stents for lymphovenous anastomosis. AB - The treatment of lymphoedema is difficult; conservative and surgical management show variable results. Lymphovenous anastomoses (LVAs) in experimental animals and patients give poor results in the treatment of primary lymphoedema and variable results in that of secondary lymphoedema. Conventional sutured LVAs were compared with anastomoses using polytetrafluoroethylene (Teflon) stents; 32 sutured and 21 stented LVAs were constructed in 16 rabbits with normal lymphatics. Anastomoses were assessed for quality and patency at 1-16 weeks by direct exposure; 27 cases were further assessed using lymphangiography. Patency in stented and sutured LVAs was 71 and 38 per cent at 1 week, and 38 and 8 per cent at 3 weeks, respectively. After 4 weeks all anastomoses were occluded. The quality of stented LVAs seemed to be higher than that of sutured LVAs. Stented LVAs are feasible and probably superior to conventional sutured LVAs. However, the patency of LVAs is of short duration because of the disadvantageous pressure gradient from lymphatics to veins, and this limits their clinical application. PMID- 1643470 TI - Abdominal aortic aneurysm, glaucoma and deafness: a new familial syndrome. AB - Several reports have suggested a genetic basis for the distribution of abdominal aortic aneurysm (AAA) in some families. The familial clustering of this disease is further demonstrated in this report of ten siblings, five of whom have confirmed AAA. This is the largest cluster so far reported. The majority of patients in this family group also have glaucoma and/or deafness. PMID- 1643471 TI - Selective use of a right retroperitoneal approach to abdominal aortic aneurysm. AB - The repair of infrarenal abdominal aortic aneurysm by right retroperitoneal dissection using a standard midline transperitoneal incision has previously been described but its clinical application has not been evaluated. Over a 14-year period 144 elective abdominal aortic aneurysm grafts were performed by a single surgical firm. Of these, 11 were carried out by a right retroperitoneal exposure (seven men and four women, aged 63-81 (median 70) years). The indications were to improve access for large juxtarenal aneurysms (n = 6) and because of dense abdominal adhesions (n = 3), horseshoe kidney (n = 1) and retroperitoneal fibrosis (n = 1). In each instance, good proximal control of the aorta was achieved. There were no major operative or postoperative complications and all patients were discharged from hospital (median stay 15 days). Follow-up (median 29 months) has revealed no procedure-related complications. PMID- 1643472 TI - Distribution of aortic diameter in a screened male population. AB - Between September 1990 and August 1991, 2291 men aged 65 years were invited for ultrasonographic screening of the aorta in the Gloucestershire aneurysm screening programme; 1748 (76.3 per cent) attended. An aortic diameter less than or equal to 2.5 cm was found in 1547 (88.5 per cent); 174 (10.0 per cent) had diameters in the range 2.6-4.0 cm, and 26 (1.5 per cent) had diameters greater than 4.0 cm. The mean(s.d.) aortic diameter was 2.1(0.55) cm and 97.5 per cent of patients had a diameter less than or equal to 3.3 cm. Any man over the age of 65 years with an aortic diameter greater than 3.3 cm has an aortic aneurysm. PMID- 1643473 TI - Thoracoscopic enucleation of leiomyoma of the oesophagus. PMID- 1643474 TI - Delayed surgery for congenital diaphragmatic hernia. AB - Between January 1987 and December 1990, 67 neonates were treated for congenital diaphragmatic hernia, symptomatic within 6 h of birth. The mortality rate was 33 per cent. Preoperative stabilization was achieved in 47 patients, all of whom survived initial treatment, although two died later. Stabilization could not be achieved in 20 neonates, all of whom died within 3 days of birth, 18 without undergoing operation and two after early repair. Intensive resuscitation with controlled, delayed operation for congenital diaphragmatic hernia gives long-term results similar to those of urgent operative repair. This approach avoids operation in the majority of those who subsequently die. PMID- 1643475 TI - Mirizzi syndrome managed by endoscopic stenting and laparoscopic cholecystectomy. PMID- 1643476 TI - Effect of biliary decompression on reticuloendothelial function in jaundiced rats. AB - The recovery of reticuloendothelial system (RES) function following decompression of obstructive jaundice was studied using a rat model with bile duct ligation and side-to-side choledochoduodenostomy. Histopathological changes in the liver were still present 5 weeks after relief of jaundice, while results of liver function tests had returned to normal. RES function evaluated by the blood clearance and organ uptake of radiolabelled Escherichia coli using a corrected phagocytic index gradually returned to normal following biliary decompression. The severely impaired RES activity noted 1 week after operation may explain the increased incidence of sepsis and renal insufficiency in the early period after biliary surgery in jaundiced patients. PMID- 1643477 TI - Treatment of common bile duct stones using mono-octanoin. AB - A retrospective analysis of 48 patients undergoing mono-octanoin infusion via nasobiliary catheter following failure of endoscopic extraction of common bile duct stones is reported. Among 35 patients who received a complete course of treatment, nine (26 per cent) had duct clearance by the completion of the infusion and a further eight on subsequent endoscopic retrograde cholangiopancreatography (ERCP) (total 49 per cent). Two patients had a successful stone extraction after enlargement of the sphincterotomy (total non surgical clearance rate 54 per cent). None of five patients with stones greater than 2 cm in diameter had stone clearance at the completion of the infusion and only one at subsequent ERCP. Among 13 patients receiving an incomplete course of treatment seven had clear ducts on repeat ERCP (54 per cent). Mono-octanoin infusion via a nasobiliary catheter is of limited value in the management of this difficult group of patients, although it may be successful in some. PMID- 1643478 TI - Risk factors and classification of acute suppurative cholangitis. AB - A prospective study was performed in 1282 patients with common bile duct stones to determine the clinical and laboratory parameters that could predict cholangitis, and the factors associated with greater severity of cholangitis. Patients were divided into two groups, with or without acute cholangitis, depending on the macroscopic appearance of bile aspirated from the common bile duct during surgery. Acute cholangitis was diagnosed when the aspirated fluid was turbid or clearly pus; the typical Charcot's triad was present in only 22 per cent of patients with acute cholangitis. Several clinical and laboratory parameters were significantly more common in these patients and, depending on their number, the probability of acute cholangitis increased significantly. The operative mortality rate was 1.2 per cent for patients without cholangitis and 11.9 per cent for patients with cholangitis. Depending on the number of factors present, patients with cholangitis were divided into three groups: mild acute cholangitis without mortality; moderate acute cholangitis with a mortality rate of 5.6 per cent; and severe acute cholangitis with a mortality rate of 27.5 per cent. The present classification allows the group of patients needing prompt endoscopic or surgical drainage to be identified. PMID- 1643479 TI - Identification of the regional lymphatic system of the gallbladder by vital staining. AB - In 21 patients with biliary tract cancer dye was injected into the lymphatic system of the gallbladder to determine the extent of its regional lymph nodes. A volume of 0.1-0.3 ml 1 per cent indigo carmine solution was injected directly into lymphatic vessels of the gallbladder in eight patients and into lymph nodes (cystic node or pericholedochal nodes) in 13 patients during radical surgery for biliary tract cancer. The lymphatic system was visualized in a total of 14 patients. The dye descended around the bile duct, flowed into the cystic node, the pericholedochal nodes and the lymph nodes posterior to the head and neck of the pancreas, and finally reached the interaortocaval nodes adjacent to the left renal vein. The stained lymphatic tissue was regarded as the regional lymphatic system of the gallbladder. These nodes should be completely resected during radical surgery for gallbladder cancer. PMID- 1643480 TI - Bile duct stents in the management of hepatolithiasis with long-segment intrahepatic biliary strictures. AB - Biliary stricture represents a challenging problem in the treatment of hepatolithiasis because of its association with treatment failure and stone recurrence. The long-segment type of stricture is difficult to manage and is likely to recur. To investigate the necessity for biliary stenting after balloon dilatation therapy, 20 consecutive patients with long-segment strictures who had 22 stents (group 1) were compared with ten patients who refused stenting (group 2). The long-segment strictures in group 1 were located on the right side in 80 per cent of patients, on the left side in 10 per cent, and were bilateral in 10 per cent. The stents, varying from 8 to 12 Fr, were retained for at least 6 months. They were inserted through the routes of a matured T tube track (five cases), percutaneous transhepatic track (14 cases), a jejunal limb (two cases) and a fistula (one case). Complications of stenting consisted of dislodgement (one case), haemobilia (two cases), cholangitis (two cases) and intrahepatic abscess (one case). The cumulative probability of stricture recurrence in group 1 was 10 per cent, 15 per cent and 21 per cent at 2, 3 and 4 years, respectively, whereas in group 2 it was 80 per cent at 2 years (P less than 0.003). The results suggest that intrahepatic biliary stenting after balloon dilatation appears necessary and helpful in the management of hepatolithiasis with long-segment biliary strictures. PMID- 1643481 TI - Bilateral pancreaticopleural fistulae treated by distal pancreatectomy. PMID- 1643482 TI - Vascular inflow exclusion and hepatic resection. AB - Seventy-nine patients undergoing hepatic resection without manipulation of the vena cava were divided into three groups. Group 1 consisted of 32 patients in whom hepatic hilar vascular exclusion was not performed. Group 2 (20 patients) had vascular inflow exclusion performed at the operative site only (right or left unilateral exclusion). Group 3 (27 patients) had total inflow exclusion during hepatic resection. There were no significant differences between the groups in blood loss or blood transfusion requirement. On the third day after operation, the serum glutamic-pyruvic transaminase level in group 3 was significantly higher than that in group 1 (P less than 0.01). Vascular inflow exclusion may not be essential for successful hepatic resection. PMID- 1643483 TI - Potential candidates for small bowel transplantation. AB - The number of potential candidates for small bowel transplantation in the UK is unknown. Potential recipients are those with irreversible small intestinal failure, including those treated with permanent parenteral nutrition. This study of one of the largest groups of patients receiving such nutrition identified ten of 25 adult patients as possible recipients. The remaining 15 were considered unsuitable, mainly because of multiple previous abdominal operations or abscesses. Extrapolation of these data to national figures on the incidence of irreversible small intestinal failure suggests that each year up to 20 new adult patients in the UK might benefit from small bowel transplantation. PMID- 1643484 TI - Perforation of the bowel by suction drains. PMID- 1643486 TI - Mesosigmoplasty as a definitive operation for sigmoid volvulus. AB - In a prospective study, 126 patients with sigmoid volvulus were treated by mesosigmoplasty during a 12-year period. Patients with sigmoid volvulus with no clinical evidence of gangrene were selected for study, and all were given a trial of non-operative reduction by proctoscopy and passage of a rectal tube. Reduction was achieved in 48 patients (38 per cent), who were subsequently treated by mesosigmoplasty as an elective procedure 1-2 weeks later. For the remaining 78 patients (62 per cent) who were not relieved by the non-operative method, emergency mesosigmoplasty was performed. There was one death in the emergency group, and two patients had a recurrence after 2 and 6 months respectively in the elective group, in whom resection was carried out. In the other 123 patients during a maximum follow-up of 12 (mean 8.2) years no recurrence was detected. Mesosigmoplasty has the advantage of low rates of mortality, morbidity and recurrence; it can be carried out as either an emergency or an elective procedure. PMID- 1643485 TI - Flush aortic tie versus selective preservation of the ascending left colic artery in low anterior resection for rectal carcinoma. AB - The effects of two methods of colonic vascular ligation were studied in 143 consecutive patients who underwent low anterior resection with total mesorectal excision and full mobilization of the splenic flexure. Either the ascending left colic artery (ALCA) was selectively preserved (n = 52) or a flush aortic ligation was performed (n = 91). In those with a protective colostomy, the radiological leak rate was 12 per cent when the ALCA was preserved (n = 41) and 10 per cent when a flush aortic tie was performed (n = 60) (P greater than 0.95; 95 per cent confidence interval (c.i.) for difference -10 to +15 per cent). In those without a colostomy, the clinical leak rates of 9 per cent when the ALCA was preserved (n = 11) and 19 per cent when a flush aortic tie was performed (n = 31) were not significantly different (P greater than 0.10; 95 per cent c.i. for difference -12 to +32 per cent). Proportional hazards analysis showed no association between the method of vascular ligation and the risk of tumour recurrence and death. Anastomotic leak rates, tumour recurrence and survival were not related to the method of vascular ligation. PMID- 1643487 TI - Primary versus staged resection for acute obstructing colorectal carcinoma. AB - The management of 115 patients with complete neoplastic obstruction of the colon was studied retrospectively. Primary resection was carried out in 40 patients, 22 with right-sided and 18 with left-sided tumours. Staged resection was planned in 48 patients and actually performed in 40. Creation of a stoma only was carried out in 25 patients because of advanced disease. There were no differences between primary and staged resection regarding the patients' general condition, concurrent disease, tumour stage according to Dukes' classification, postoperative complications, or mortality. The postoperative mortality rate was 10 per cent after primary and 15 per cent after staged resection (P not significant). The median hospital stay was 18 and 45 days, respectively. The 5 year survival rate was 38 per cent after primary and 29 per cent after staged resection. All primary resections but one were performed by qualified surgeons, while trainees created stomas as emergency treatment. The similarity in outcome suggests that in future this condition should, where possible, be treated by primary resection, by surgeons experienced in colorectal operations. PMID- 1643488 TI - Pouch advancement and neoileoanal anastomosis for anastomotic stricture and anovaginal fistula complicating restorative proctocolectomy. PMID- 1643489 TI - Brighton modification of the DeBakey aortic clamp. PMID- 1643490 TI - Estimation of small bowel transit time following colectomy and ileal reservoir construction. AB - A study was carried out to evaluate the breath hydrogen test as a method of estimating small bowel transit in patients with an ileal pouch and to determine whether gut transit time influenced functional outcome. Twelve patients with an ileal reservoir and ten control subjects ingested a test meal of 400 ml chicken soup, 20 g lactulose and 50 ml dilute barium solution. Concurrent breath hydrogen testing and radiological screening was carried out until the head of the test meal reached the ileal pouch or caecum. At the time that the test meal arrived in the pouch, faecal anaerobic bacterial counts were obtained. Pouch compliance, functional capacity and anal sphincter pressures were also measured. While there was an excellent correlation between radiological and breath hydrogen measures of orocaecal transit time in controls (P less than 0.001), no such relationship was found for oropouch transit. Four of the 12 patients with a pouch produced no hydrogen after test meal ingestion, while in two other such patients breath hydrogen peaks occurred when the head of the meal was in the jejunum. The magnitude of the breath hydrogen rise in patients with an ileal pouch correlated well with faecal anaerobic bacterial counts (P less than 0.01). The median (95 per cent confidence interval) radiological small bowel transit time was more rapid in patients with a pouch than in control subjects: 28 (23-33) versus 72 (46 86) min (P less than 0.01). Increased 24-h frequency of defaecation was associated with more rapid small bowel transit after ileal reservoir construction (P less than 0.01) but correlated with neither pouch capacity nor compliance. These data show that small bowel transit time may be a determinant of ileal pouch function but that breath hydrogen estimation of gut transit time in patients with an ileal reservoir is unreliable. PMID- 1643491 TI - Subcutaneous rectal stump closure after emergency subtotal colectomy. AB - Subtotal colectomy with preservation of the rectum is now the procedure of choice for patients with severe colitis requiring emergency surgery. The use of subcutaneous 'rectal closure' when the retained distal bowel is placed at the caudal end of the abdominal incision in the subcutaneous or fascial layer is studied. An anal catheter may be placed to drain the rectum. Thirty-two patients (14 men, 18 women) of mean age 33 (range 17-77) years with severe inflammatory bowel disease (29 ulcerative colitis, one Crohn's disease, one indeterminate colitis, one Campylobacter colitis) underwent emergency colectomy with subcutaneous rectal stump closure. Twenty-three stumps were closed with staples, four sutured and five by both staples and sutures. Complications developed in seven patients (22 per cent), of which two required surgical intervention. One significant wound infection was treated successfully with a course of antibiotics. Three minor wound infections did not require specific treatment. The rectal stump was always readily located at the time of restorative surgery. This technique is recommended as a simple and safe alternative to an open mucus fistula provided that surgeons adhere to standard surgical principles; in particular the distal bowel should not be brought out into the wound under tension.